Pharmacists’ roles in providing patient care remain limited in Indonesia, hence this study aimed to determine the preparedness of pharmacy graduates from one university in Indonesia to deliver patient care. Pharmacy graduates (both registered pharmacists [104] and recent graduates eligible for registration [45]) were sent a validated self-administered survey. The survey sought their perceptions about whether they had acquired 16 patient care related attributes. Further, it sought their opinion on the desirability of having those attributes. Data were analysed using SPSS version 22.0. Sixteen of 104 (15.4%) registered pharmacists and 40 of 45 (88.9%) recent pharmacy graduates participated in the study. More than 50% of participants in both groups were female and most participants were aged in their 20s. Of the recent pharmacy graduates the majority perceived they had at least partially acquired four of 16 list attributes. Male and female recent graduates had significantly different beliefs about their leadership ability (p=0.004). In comparison, most registered pharmacists perceived they had 10 out of the 16 listed attributes. The findings of this study suggested that pharmacy graduates should be better prepared to deliver patient care, and that curriculum redesign with expansion of experiential learning is required.

(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At present, the exploration of novel therapies for alleviating diabetic neuropathy-associated pain is genuinely captivating, considering that current therapeutic options are characterized by poor efficacy and significant risk of side effects. In the current research, we evaluated the antihyperalgesic effect of sildenafil (phosphodiesterase-5 inhibitor) – metformin (antihyperglycemic agent) combination and its impact on biochemical markers in alloxan-induced diabetic neuropathy in rats; (2) Methods: The study comprised a cohort of 70 diabetic rats and 10 non-diabetic rats which were submitted to hot, cold, and tactile stimulus tests. Morover, we investigated the influence of this combination on TNF-α, IL-6 nitrites and thiols levels in brain and liver tissues; (3) Results: The results demonstrated that all sildenafil-metformin combinations decreased the pain sensitivity in von Frey test, Hot-plate test and Cold-plate test. Furthermore, alterations in nitrites and thiols concentrations and pro-inflammatory cytokines (specifically TNF-α and IL-6) were noted following a 15-day regimen of various sildenafil-metformin combinations. (4) Conclusions: The combination of sildenafil and metformin has a synergistic effect in alleviating pain in alloxan-induced diabetic neuropathy rats. Additionally, the combination effectively decreased inflammation, inhibited the rise in NOS activity, and provided protection against glutathione depletion.

Psoriasis is a chronic recurrent inflammatory autoimmune pathology, with a major genetic component and several interferences of immunological cells and their cytokines. The complex orchestration of psoriasis pathogenesis is related to the synergic effect of immune cells, polygenic alterations, the presence of autoantigens and several external factors. The major act of IL-23/IL-17 axis, strongly influencing the inflammatory pattern established during the disease activity, is visible as a continuous perpetuation of the pro-inflammatory response and keratinocyte activation and proliferation leading to the development of psoriatic lesions. Genome wide association studies (GWAS) along offered a better view of psoriasis pathogenic pathways, with approximately one third of psoriasis genetic impact on psoriasis development is associated to MHC region, with genetic loci located on chromosome 6. The most eloquent genetic factor of psoriasis, PSORS1, was identified in the MHC I site. Between the several factors involved in its complex etiology, dysbiosis, due to genetic or external stimulus, exhibiting less variety and the involvement of pathogenic bacteria, cand induce a burst of proinflammatory consequences, both cutaneous and gut microbiome being involved in psoriasis pathogenic process. A complex understanding of the major pathways that interplay in order to initiate and perpetuate psoriatic diseases and its associated comorbidities can help the current clinical practice by properly evaluating completely and individualized each patient and establish the proper therapeutic management.

Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

This study explores the complexities involved in the extraction and purification of catechins, prominent bioactive compounds found in plant extracts and tea. It addresses challenges arising from the intricate molecular structure of catechins and their inherent variability across botanical sources. Despite these obstacles, catechins present significant potential, particularly in healthcare. Their potent antioxidant properties have been extensively investigated and associated with numerous health benefits, positioning them as promising therapeutic agents for combating chronic diseases. Furthermore, catechins have diverse applications across various industries, including food and beverage, cosmetics, agriculture, and materials science. This abstract emphasizes the importance of continued research and innovation in catechin extraction and utilization, which hold promise for advancing human health and technological progress across multiple domains.

Early discharge after childbirth has led to a rise in neonatal readmission, becoming a major concern in recent decades. Our research aimed to identify the risk factors and incidence of neonatal readmission, as well as explore preventive measures. Our study at the Clinical Hospital of Pediatrics in Ploiești, Romania included 108 neonates admitted during the neonatal period. This accounted for 2.06% of all admissions (5226). The most prevalent cases were malnutrition (25%), fever (20.3%) and bronchiolitis (17.5%). Diarrhea and infectious gastroenteritis were also observed (14.8%), along with acute rhinoconjunctivitis (9.2%) and late onset sepsis (3.7%). No deaths were recorded. The most significant characteristics identified were number of children (p<0.001) and age at maternity discharge (p<0.001). By following the prevention rules, malnutrition, feeding errors, and infections can be avoided. This includes practicing proper hand hygiene for both mothers and medical staff, as well as educating and demonstrating to mothers the benefits of breastfeeding. In addition, all newborns discharged from the maternity ward should benefit from follow-up at 7-10 days of life. Our results confirm the effectiveness of a multidisciplinary team and endorse promoting breastfeeding. Implementing quality control measures and regularly evaluating the surveillance program will help improve its effectiveness.

Objective: The aim of this study was to optimize the fermentation process of Radix Ranunculi ternate via microbial fermentation and analyze the changes in the contents of the main components, the antioxidant and hypoglycemic capacities of the extract before and after fermentation. Methods: The solid-state fermentation process was optimized using single-factor tests and the response surface method, with the yield of the alcohol extract of R. ternate as an evaluation index. Results: The best fermentation process was optimized using solid-state endophytic fungus fermentation technology as follows: strain addition ratio of Chaetomium globosum/Fusarium equiseti =1:1, fermentation for 5 d, sieve size of 40 mesh, liquid/material ratio of 0.8:1 mL·g−1, fermentation temperature of 31 °C, and inoculation amount of 7.5%. Under the optimized conditions, the contents of the water-soluble extract and total polysaccharides decreased by 12.71% and 12.95%, respectively, in the fermentation, The contents of ethanol-soluble-extract, flavonoids, saponins, polyphenols, organic acids, and total amino acids of fermented R. ternate increased by 19.77%, 57.14%, 79.67%, 14.29%, 17.63% and 3.82%, respectively, and the scavenging rate for DPPH, ABTS+, ·OH free radicals and inhibitory rate for α-amylase also increased by 19.02%, 14.17%, 7.53% and 34.54%, respectively, compared with unfermented R. ternate. Conclusions: Solid-state fermentation opens new avenues for the development and application of R. ternate as natural antioxidant and hypoglycemic food.

Considering the worldwide impact of heart failure, it is crucial to develop approaches that can help us comprehend its root cause and make accurate predictions about its outcome. This is essential for lowering the suffering and death rates connected with this widespread illness. Cardiomyopathies frequently result from genetic factors, and the study of heart failure genetics is advancing quickly. Dilated cardiomyopathy (DCM) is the most prevalent kind of cardiomyopathy, encompassing both hereditary and nongenetic abnormalities. It is distinguished by the enlargement of the left ventricle or both ventricles, accompanied by reduced contractility. The discovery of the molecular origins and subsequent awareness of the molecular mechanism is broadening our knowledge of DCM development. Additionally, it emphasizes the complicated nature of DCM and the necessity to formulate several different strategies to address the diverse underlying factors contributing to this disease. Genetic variations that can be transmitted from one generation to another can be a significant contributor to causing family or isolated DCM. Genetic variation also plays a significant role in determining susceptibility for acquired triggers for DCM. The genetic causes of DCM can have a diverse range of phenotypic expressions. It is crucial to select the most probable patients to have advantages from genetic testing. The purpose of this research is to emphasize the significance of identifying genetic DCM, the crucial relationships between genotype and phenotype, and the usefulness of genetic testing in the therapeutic care of both those affected and their relatives. This approach is expected to gain importance once treatment is guided by genotype-specific advice and disease-modifying medications.

Air pollution, climate change and global warming show direct linkage. Introduction - Background: Research in the field has proposed and demonstrated their link to increased allergenicity in plants, leading to increased allergic diseases. Allergen patterns are changing in response to climate change. Across Europe, up to 12% of the population suffers from allergic diseases (bronchial asthma and allergic rhinitis) caused by the pollen grains. The medical costs of these types of allergies are enormous and are increasing with the spread of common ragweed - Ambrosia artemisiifolia* in Europe. In practice, more and more patients are turning to allergists. Methods: Based on these data, the research aims to identify safety measures and specific legislation to control and eradicate common ragweed in the countries most affected by the spread of this plant in Europe, increase in population exposure in countries affected by the presence of common ragweed and the socio-economic impact of allergic rhinitis and bronchial asthma at European level.[1][2] Our database search did not reveal any other research that has addressed this topic to date. Results: This research identifies specific legislation to the countries most affected by the spread of this plant pollen grains at European level, changes in allergen patterns and monitoring/safety eradication measures decided by local authorities, and data on the spread of common ragweed over the last two decades, costs per treatment, increased allergic rhinitis and bronchial asthma morbidity in the most affected areas. Conclusions: At European level, there are no universally valid models for eradicating this weed. Various methods can be used to limit the spread of common ragweed and its pollen production (e.g. mowing once or twice a year of overgrown land, ploughing, chemical control, public information, etc.). Local and regional cooperation should be considered essential to promote phytosanitary & safety measures and exchange of information on methods to identify and manage the spread of common ragweed. Unified legislation at European level would help all affected countries; reduce morbidity from respiratory allergic diseases and the costs of treating these diseases.

(1) Background: As part of the Scottish Governments five-year recovery plan to address the backlog in NHS care following the COVID-19 pandemic, community pharmacies in Scotland are planned to provide a Hospital Discharge Medicines Supply and Medicines Reconciliation Service. We aimed to qualitatively explore patients’ experience of this new service; (2) Method: Adult patients (≥18yrs age) who consented to participate in the Community Pharmacy Hospital Dis-charge and Medicines Reconciliation Service were invited for interview within 21 days of dis-charge from hospital. Qualitative, one-to-one, semi-structured, patient interviews were conducted by telephone and audio-recorded using Microsoft Teams®. The interview audio recordings were transcribed verbatim and underwent thematic analysis; (3) Results: 12 patients were inter-viewed, evenly split by sex and with a median age of 62 years (range; 36 to 88 years). Analysis generated main five themes; Patient Engagement, Stakeholder Communication, Practical Factors, Human Factors, and Comparative Experiences. Many of these were interdependent; (4) Con-clusions: Patients appreciated that the service ensured a quicker discharge from hospital. Good stakeholder communication, practical factors (including choice, location, and the realities of ob-taining their medication from the community pharmacy), and a pre-existing and trusted rela-tionship in their usual community pharmacy were the key factors that regulated the patient ex-perience. In the main, patients were positive about the introduction of this new service. However, a lack of previous relationship or trust with a community pharmacy, and previous experiences with medication supply problems were factors which had the potential to negatively impact on patient experiences.

Background: Peritoneal sclerosis (PS) and its most severe form, encapsulating PS (EPS), are rare entities that can occur in various procedures (liver transplantation, intraperitoneal chemotherapy), secondary to medications ( beta-blockers); however, PS or EPS typically occur in patients undergoing peritoneal dialysis as a form of renal function substitution. Medical or surgical treatments can be applied, but morbidity and mortality have high rates . This condition typically presents clinically as an intestinal obstruction caused by the inclusion of the intestinal loops in the peritoneal fibrous membrane. Methods: Herein we present data from a single tertiary surgery center that has dedicated teams for patients receiving dialysis. In 12 years we analyzed a group of 63 patients admitted for catheter replacement/removal or for acute surgical pathology. In 5 cases (7,9%) we diagnosed EPS . Two patients with EPS presented with atypical abdominal pathologies requiring emergency surgery: one case of hemoperitoneum caused by a ruptured ovarian cyst and one case of uterine fibroids and metrorrhagia. Results: The definitive diagnoses were established intraoperatively and by analyzing the morpho-pathological changes of the peritoneum. The possible intraoperative challenges included laborious dissection, difficulties in restoring the correct anatomical landmarks, increased duration of the surgical intervention and a high rate of incidents and accidents Conclusions: The aim of the present study was to emphasize the possibility of other surgical pathologies overlapping with EPS, increasing the complexity of the surgical intervention. Also, we sought to determine whether there is a correlation between the morpho-pathological results of these patients who underwent emergency surgery and the common EPS morpho-pathological changes.

Genome-wide association studies (GWAS) have successfully revealed numerous susceptibility loci for obesity. PREDATORR study (2014) shows that in Romania, 34,6% of adults aged 20-79 y/o are overweight, 31,4% are obese with a high risk of cardiometabolic complications, a number that puts almost 67% of Romania's population in the abnormal weight group. Our study aims to investigate the current staus of genetic foundation in metabolic disease associated with obesity, applied to a pilot group of patients specifically examining the impact of known polymorphisms and their haplotype of six food intake-regulating genes: leptin (LEP), leptin receptor (LEP-R), serotonin receptor (5HTR2A), ghrelin (GHRL), neuropeptide Y (NPY) and fat-mass and obesity-associated (FTO) with the following polymorphisms: LEP A-2548G, LEPR A-223G, 5HTR2A G-1439A, GHRL G-72T, NPY T-29063C, FTO A-T and body mass index (BMI). A notable link between the LEP-2548 rs7799039 gene's AG genotype and the risk of obesity was observed, particularly pronounced in males aged 40-49, with an approximately sevenfold increased likelihood of obesity. The 5HTR2A rs6311 AA genotype was associated with a higher BMI, not statistically significant. The FTO rs9939609 gene's AA genotype emerged as a significant predictor of obesity risk. Besides these significant findings, no substantial associations were observed with the LEPR, 5HTR2A, GHRL and NPY genes. Haplotype association analysis showed a suggestive indication of GRGMLA (rs7799039, rs1137101, rs6311, rs696217, rs16139, rs9939609 sequence) haplotype with susceptibility effect towards obesity predisposition. Linkage disequilibrium (LD) analysis showed statistically significant associations between LEP and LEPR gene (p = 1e-04), LEP and GHRL gene (p = 0.0047), GHRL and FTO gene (p=0.03). The outcomes of this study, to our knowledge, one of the very few on the Romanian population, aimed to be a starting point for further research on the targeted interventional strategies to reduce cardiometabolic risks.

Curcumin, a hydrophobic polyphenol compound derived from the rhizome of the Curcuma genus, has a wide spectrum of biological and pharmacological applications. Previously, curcumin nanoparticles with different stabilizers had been produced successfully in order to enhance solubility and per oral absorption. In the present study, we tested the anti-inflammatory effect of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)-stabilized curcumin nanoparticles in vivo. Lambda-carrageenan (λ-carrageenan) was used to induce inflammation in rats; it was given by an intraplantar route and intrapelurally through surgery in the pleurisy test. In the λ-carrageenan-induced edema model, TPGS-stabilized curcumin nanoparticles were given orally one hour before induction and at 0.5, 4.5, and 8.5 h after induction with two different doses (1.8 and 0.9 mg/kg body weight (BW)). Sodium diclofenac with a dose of 4.5 mg/kg BW was used as a standard drug. A physical mixture of curcumin-TPGS was also used as a comparison with a higher dose of 60 mg/kg BW. The anti-inflammatory effect was assessed on the edema in the carrageenan-induced paw edema model and by the volume of exudate as well as the number of leukocytes reduced in the pleurisy test. TPGS-stabilized curcumin nanoparticles with lower doses showed better anti-inflammatory effects, indicating the greater absorption capability through the gastrointestinal tract.

Malocclusions have a continuously increasing prevalence from a generation to another as a result of climate changes, soil, atmosphere and water pollution. All of these aspects have unfavorable consequences on the nutritional scheme. Thus, nutrition together with other etiopathogenic factors contribute to complex alterations in the somatic development of the entire organism and, implicitly, of the cephalic extremity. The study group included 4147 children from randomly selected schools from Vâlcea County, Romania. The aim of this study is to determine the prevalence of malocclusions in schoolchildren from Vâlcea County, Romania, according to the three main classes of malocclusions (according to Angle’s classification), age groups (from 6 to 10 years old and from 11 to 14 years old), gender (male and female) and place of origin (rural and urban). For Angle class I malocclusions we recorded the highest prevalence (48,78% from the total number of schoolchildren with malocclusions), followed by Angle class II malocclusions (45,85% from the total number of schoolchildren with malocclusions) and for Angle class III malocclusions we found the lowest prevalence (5,37% from the total number of schoolchildren with malocclusions).According to gender, we found the highest prevalence in female gender (29,90% from the total number of female subjects), while in male gender we recorded a prevalence of 27,70% from the total number of male subjects. Regarding the place of origin, there is a higher prevalence of malocclusions in the urban areas (29,16%). The study subgroup included 140 children randomly selected from the total number of subjects from the study group. They were included in a more advanced study. The aim is to find potential associations between the presence of malocclusions and various oral variables. Categorical variables were expressed as numerical values and percentages, and their association was evaluated with either the Chi-square test of association or homogeneity, or the Fisher Exact test. The acquired data were incorporated into a binomial logistic regression model to assess the likelihood of developing malocclusions in relation to the following variables: defective phonation, bruxism, frequency of teeth brushing, onychophagia, oral respiration, infantile deglutition, placing objects between the maxillaries, thumb sucking and salivary aspects. It is also aimed to compare the results obtained with similar ones from the specialized literature.

Berberis vulgaris (L.) has remarkable ethnopharmacological properties and is widely used in traditional medicine. The present study investigates B. vulgaris stem bark (Berberidis cortex) by extraction with 50% ethanol. The main secondary metabolites were quantified, resulting in a polyphenols content of 17.6780 ± 3.9320 mg Eq Tannic acid / 100 g extract, phenolic acids amount of 3.3886 ± 0.3481 mg Eq Chlorogenic acid / 100 g extract and 78.95 µg/g berberine. The dried hydro-ethanolic extract (BVE) was thoroughly analyzed using Ultra-High Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry (UHPLC–HRMS/MS) and HPLC and 40 bioactive phenolic constituents were identified. Then, the antioxidant potential of BVE was evaluated using three methods; our results could explain the protective effects of Berberidis cortex EC50FRAP = 0.1398 mg/mL, IC50ABTS = 0.0442 mg/mL, IC50DPPH = 0.2610 mg/mL compared to ascorbic acid (IC50 = 0.0165 mg/mL). Next, the acute toxicity and teratogenicity of BVE and Berberine - Berberine sulfate hydrate (BS) - investigated on Daphnia sp reported significant BS toxicity after 24 h; BVE revealed considerable toxicity after 48 hours and induced embryonic developmental delays. Finally, the anticancer effects of BVE and BS were evaluated on different tumor cell lines after 24 and 48 hours of treatments. The MTS assay evidenced a dose- and time-dependent antiproliferative activity, higher on BS than BVE. The strongest diminution of tumor cell viability was recorded on breast (MDA-MB-231), colon (LoVo) cancer, and OSCC (PE/CA-PJ49) cell lines after 48 h of exposure (IC50 < 100 µg/mL). However, no cytotoxicity was reported on normal epithelial cells (HUVEC) and hepatocellular carcinoma (HT-29) cell lines. Extensive data analysis supports our results, showing a significant correlation between the BVE's concentration, phenolic compounds content, antioxidant activity, exposure time, and the viability rate of various normal cells and cancer cell lines.

Groove pancreatitis represents a chronic focal form of pancreatitis affecting the zone between the pancreatic head and the duodenal „C” loop, known as the groove area. This is a rare condition that affects the pancreatic periampullary part, including the duodenum and the common bile duct, associated usually with long-term alcohol and tobacco misuse and being more frequent in men than in women. The most common clinical symptoms of groove pancreatitis include weight loss, acute abdominal pain, nausea, and jaundice. This report is about a 66 year old woman with a history of heavy smoking, presenting with weight loss, nausea, and upper abdominal pain. Contrast enhanced computed tomography revealed the existence of a chronic pancreatitis as well as the dilatation of the main pancreatic duct, a cyst of the pancreatic head and enlargement of the biliary tract. Conservatory treatment was initiated but with no improvement of symptoms. Since there was no indication for endoscopic retrograde cholangiopancreatography, we decided to perform a pancreatoduodenectomy, as surgery appears to be the single effective treatment.

Background: The Liver Imaging Reporting and Data System (LI-RADS) combines standardized terminology with a classification system for imaging findings in patients with HCC, therefore rendering diagnostic biopsy unnecessary in many cases. This retrospective study included 23 patients with a biopsy diagnosis of HCC, performed either before or after local interventional procedures, in order to evaluate the histopathologic changes induced by previous procedures and their potential influence on the response to immune therapy. Material and Methods: The study encompassed a cohort of patients diagnosed with Hepatocellular Carcinoma (HCC). Diagnosis was established through contrast-enhanced computer tomography or magnetic resonance imaging that identified LI-RADS-5 nodules in conjunction with historical liver disease and elevated alpha-fetoprotein (AFP) levels, or through histological examination confirming positivity for glypican3, heat shock protein70, and glutamine synthetase. The study detailed the liver disease etiology, LI-RADS scores, characteristics and dimensions of HCC nodules, serum AFP concentrations, Edmondson-Steiner grading, and the expression of programmed cell death ligand 1 (PD-L1) in the tumor cells. Results: Among the study's cohort of Hepatocellular Carcinoma (HCC) patients, a portion had not received any prior treatments, while the remainder experienced local HCC recurrence following trans-arterial chemoembolization or radiofrequency ablation. Observations indicated elevated alpha-fetoprotein (AFP) levels in those who had not undergone any previous interventions, showing statistical significance. The Edmondson-Steiner classification predominantly identified grade III differentiation across patients, irrespective of their treatment history. Furthermore, an increase in intra-tumoral programmed cell death ligand 1 (PD-L1) expression was noted in patients who had not been subjected to previous therapies. Conclusion: Liver biopsy offers valuable insights for patients with Hepatocellular Carcinoma (HCC), assisting in the tailoring of immune therapy strategies, particularly in cases of recurrence following prior local interventions.

Background and Objectives: Knee osteoarthritis (KOA) is a degenerative disease that is targeting continuously people of different ages, but especially the elderly population, the number of which tends to increase continuously at the global level. Apart from age, excess weight can influence the evolution of the disease, with obesity being associated with a weak inflammation stage, and an imbalance between pro-inflammatory and anti-inflammatory cytokines. The present work aimed to identify specific biomarkers alike ACRP-30, IL-10, TNF-α, and IL-6 in synovial fluid and correlate them with patients’ clinical data. Materials and Methods: 24 subjects with KOA and over 50 years of age are involved in the present study. All patients performed a supine X-ray at the target knee. Ultrasound was performed using an ESAOTE MyLab Omega (ESAOTE Spa, Italy) ultrasound device and a 6-19 MHz linear array transducer. Results: The obtained results highlighted a significant correlation between age and adiponectin level (p=0.0451, r=-0.412). Also, the IL-10 values are lower in cases where the intensity of the pain is more pronounced (p=0.0405, r=-0.421). In addition, analyzing the data by gender, it was observed that in the case of males, stiffness is more related to age (p=0.0079, r=0.7993), compared to women (p=0.0203, r=0.6223). In the case of women, the progression of the disease tends to increase more intensively total WOMAC score’s values (p=0.00031, r=0.8342), compared with men (p=0.0289, r=7013). Regarding interleukins and BMI, significant correlations were observed only in the case of men. Conclusions: A significant correlation between age and adiponectin, and adiponectin and IL-6, suggests that advanced age may contribute to adiponectin reduction. Comparing men with women, it was observed that men's age is more related to rigidity, and IL-6 and IL-10 are directly correlated to BMI and women seem to be more sensitive to pain and stiffness.

Although ovarian cystic teratoma is the most common ovarian tumor, complications are quite rare. However, it is important to be recognized by the radiologist in order to avoid inaccurately diagnosing them as malignant lesions. This case report describes a 61-year-old postmenopausal woman, who presented to the emergency room with abdominal pain following a minor blunt abdominal trauma. In this context, a CT scan was performed, which showed the presence of round, hypodense masses randomly distributed in the peritoneum, with coexisting ascites in moderate amount; ovarian carcinoma with peritoneal carcinomatosis was suspected. The patient was hospitalized and an MRI of the abdomen and pelvis was recommended for a more detailed lesion characterization. Following this examination, the patient was diagnosed with mature cystic ovarian teratoma complicated by rupture. Surgery was performed, and the outcome was favorable. The cases of ruptured cystic teratomas are rare, and to our knowledge, this is the first occurrence described in literature. Special attention must be paid when confronting with such a case in medical practice, since it can easily misdiagnosed as peritoneal carcinomatosis

Background: The modified Duke index derived from coronary computed tomography angiography (CCTA) was designed to predict cardiovascular outcomes based on the severity of coronary ste-nosis. However, it does not take into consideration the presence or severity of peri-coronary in-flammation. The peri-coronary fat attenuation index (FAI) is a novel imaging marker determined by CCTA which reflects the degree of inflammation in the coronary tree in patients with coronary artery disease. Purpose: To assess the association between the modified Duke index assessed by CCTA, cardiovascular risk factors and peri-coronary inflammation in the coronary arteries of pa-tients with coronary artery disease. Methods: One hundred seventy-two patients who underwent CCTA for typical angina were assigned into two groups based on the modified Duke index: group 1 – patients with low index ≤ 3 (n=107) and group 2 – patients with high index > 3 (n=65). Demo-graphic, clinical and CCTA data were collected for all patients, and FAI analysis of coronary in-flammation was performed. Results: Patients with increased values of the modified Duke index were significantly older compared to those with a low index (61.83 ± 9.89 vs. 64.78 ± 8.9; p = 0.002). No differences were found between the two groups in terms of gender distribution, hypertension, hypercholesterolemia or smoking history (all p > 0.5). The FAI score was significantly higher in patients from group 2, who presented a significantly higher score of inflammation compared to the patients in group 1, especially at the level of the right coronary artery (FAI score 20.85 ± 15.80 vs. 14.61 ± 16.66; p = 0.01 for the right coronary artery, 13.85 ± 8.04 vs. 10.91 ± 6.5; p = 0.01 for the circumflex artery, and 13.26 ±10.18 vs. 11.37 ± 8.84; p = 0.2 for the left anterior descending artery). CaRi-Heart® analysis identified a significantly higher risk of future events among patients with a high modified Duke index (34.84 % ± 25.86 % versus 16.87 % ± 15.80 %; p

Background and Objectives: The purpose of this study was to investigate whether early surfactant administration affects the status of ductus arteriosus (DA) in preterm infants ≤32 weeks of gestational age (GA) within 24 hours of birth. Materials and Methods: It is a prospective study conducted from March 15, 2022, to November 15, 2023, in a tertiary academic center. In-born infants ≤ 32 weeks of gestation (n = 88) were enrolled. The study group was further divided into surfactant (n=44) and non-surfactant (n=44) subgroups. Results: 76% of the preterm infants who received surfactant therapy (RRR = 0.839) recorded an increase in Kindler Score at 24 hours of life (1-RR = 1-0.24 = 76%). Surfactant administration was significantly associated with decreased pre-ductal diastolic pressure (29.9 mmHg vs. 34.8 mmHg, p=0.0231), post-ductal diastolic pressure (28.7 mmHg vs. 32.2 mmHg, p=0.0178) pre-ductal MAP (41.6 mmHg vs. 46.5 mmHg, p=0.0210) post-ductal MAP (41.0 mmHg vs. 45.3 mmHg, p=0.0336). There were no significant changes in ductus arteriosus parameters at 24 hours of life. Conclusions: Early surfactant administration does not affect the status of ductus arteriosus in preterm infants ≤32 weeks of gestational age at 24 hours of life.

This review aims to explore the intricate relationship between epigenetic mechanisms, stress, and affective disorders, focusing on how early life experiences and coping mechanisms contribute to susceptibility to mood disorders. Epigenetic factors play a crucial role in regulating gene expression without altering the DNA (deoxyribonucleic acid) sequence, and recent research has revealed associations between epigenetic changes and maladaptive responses to stress or psychiatric disorders. A scoping review of 33 studies employing the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses – Statement) guidelines investigates the role of stress-induced epigenetic mechanisms and coping strategies in affective disorders' occurrence, development, and progression. The analysis encompasses various stress factors, including childhood trauma, work-related stress, and dietary deficiencies, alongside epigenetic changes such as DNA methylation and altered gene expression. Findings indicate that specific stress-related genes frequently exhibit epigenetic changes associated with affective disorders. Moreover, the review examines coping mechanisms in patients with bipolar disorder and major depressive disorder, revealing mixed associations between coping strategies and symptom severity. While active coping is correlated with better outcomes, emotion-focused coping may exacerbate depressive or manic episodes. Overall, this review underscores the complex interplay between genetic predisposition, environmental stressors, coping mechanisms, and affective disorders. Understanding these interactions is essential for developing targeted interventions and personalized treatment strategies for individuals with mood disorders. However, further research is needed to elucidate specific genomic loci involved in affective disorders and the clinical implications of coping strategies in therapeutic settings.

Background and Objectives Neurofibromatosis 1 (NF1 MIM # 162200), also known as von Recklinghausen disease, is among the most common autosomal dominantly transmitted disorders characterized mainly by neurocutaneous manifestations such as café au lait spots, intertriginous freckling, various types of neurofibromas (cutaneous neurofibromas or plexiform tumors), neurological manifestations, and bone abnormalities. It occurs with an incidence of 1:3000–1:4000 cases. Cone-rod dystrophies belong to the large group of retinal dystrophies, a highly heterogeneous group of disorders clinically manifested mainly by damage to cone and rod cells and have a broad spectrum of clinical manifestations. Many genes are involved in their etiology, with more than 100 currently identified, including the CRX gene responsible for the autosomal dominant form of cone-rod dystrophy (ad CORD). Materials and Methods: The authors present an intriguing case of a patient diagnosed with Neurofibromatosis type 1 (NF1) as an infant and ocular involvement (myopia and astigmatism onset at age 15), which yielded a surprising molecular testing result. Results: Molecular DNA analysis identified a rare occurrence of two mutational variants, including a pathogenic variant in the NF1 gene, c.3871-2A, and a likely pathogenic variant in the CRX gene c.119G>A. Conclusions: The authors present this case to highlight the surprises offered by molecular testing in a condition where the diagnosis is usually based on clinical criteria, thus providing patients with competent genetic advice.

(1) Background: The prediction of cervical lesions evolution is a challenge for clinicians. The prospective study aimed to determine and compare the predictive accuracy of cytology, HPV genotyping, and p16/Ki67 dual staining alone or in combination with personal risk factors for the prediction of progression, regression or persistence of cervical lesions in human papillomavirus (HPV)-infected patients; (2) Methods: This prospective study included HPV-positive patients with or without cervical lesions that underwent follow-up. Descriptive statistics and sensitivity analysis for individual or combined index tests were used for data analysis; (3) Results: The highest predictive performance for the progression of cervical lesions was achieved by a model that comprised a Pap smear suggestive of high-grade squamous intraepithelial lesion (HSIL), the presence of 16/18 HPV strains, a positive p16/Ki67 dual staining result along with the presence of at least 3 clinical risk factors, which had a sensitivity (Se) of 74.42%, a specificity of 97.92%, an area under the receiver operating curve (AUC) of 0.961, and an accuracy of 90.65%. The prediction of cervical lesions regression or persistence was modest; (4) Conclusions: Multiple testing or new biomarkers should be used to improve HPV-positive patient surveillance, especially for cervical lesion regression or persistence prediction.

(1) Background: Thrombophilia is a tendency towards hypercoagulability, and it is increased by pregnancy, peaking around delivery. Research question: does thrombophilia stimulate the in-flammatory state of the patient, already suppressed by pregnancy? (2) Methods: Eighty thrombo-philia patients admitted for delivery between 1/10/2017 and 1/12/2021 were prospectively stud-ied, together with eighty age- and para-matched control patients. Patients were admitted for de-livery at term by means of cesarean section. The inflammation indexes from the complete blood count values analysis during both the 24 hours before and after labor—extracted from the hospi-tal’s medical records—were calculated and then correlated with uterine involution. (3) Results: Except for the PLR, most of the numerous inflammation indexes studied were not significantly different in treated thrombophilia patients, before and after delivery, compared to non-thrombophilia patients. Only when we split the patients, based on the uterine haematometra in the first 24-48 hours postpartum, we found out that the few treated thrombophilia patients with haematometra (14 with haematometra out of 79 with treated thrombophilia) had elevated SII and AISI antepartum. In pregnant patients treated for thrombophilia, MLR is higher in pa-tients without the Rh factor than in those with the Rh factor. In non-thrombophilia patients, MCVL and NLPR increased with age and before labor, while SII and AISI increased with age postpartum. (4) Conclusions: Thrombophilia did not stimulate the inflammatory state of the pa-tient, already suppressed by pregnancy.

Dirofilariosis is an infectious disease caused by species of the Dirofilaria genus. It is manifested by the appearance of a subcutaneous swelling, especially in the eye region. We present the case of a 29-year-old patient that accused facial asymmetry in the right genian region. Following clinical and paraclinical evaluations, the diagnosis of parasitic cyst was established in the context of dirofilariosis with Dirofilaria repens (D. repens). Treatment consisted of surgical excision of the formation associated with prophylactic antibiotic medication. Macroscopic analysis of the excision piece revealed a structure that contains a cystic cavity and a filamentous form with a length of approximately 10 mM and a diameter of 1 mM. This is the first case of dirofilariosis located in the genian region reported in Romania. The overview of this pathology is important to raise awareness among physicians about its presence and its clinical variations.

Neonatal mortality remains a public health concern and timely identification and prompt intervention in the delivery room could improve the outcome in neonatal morbidity and mortality. We performed a retrospective study to help us finding the profile of the high-risk newborn regarding the need for NICU admission, necessary to establish a protocol regarding the mobilization of human and material resources for the urgent management of these situations. All deliveries and neonates born in Maternity of Bihor County Emergency Clinical Hospital from Romania were reviewed, including relevant maternal, foetal and perinatal data to identify risk factors that result in birth of newborns needing resuscitation at birth between 2012-2019. The number of births showed a downward trend but around 90% of the births were on term. The incidence of neonatal emergencies is increasing, the most frequently were respiratory, sepsis and other infections, cardiovascular emergencies, and extreme prematurity. It is noted that in 2021 the incidence of these neurological emergencies increased by three times compared to previous years. The neonatal and maternal risk factors associated with admission to the NICU were mother's age over 35 years, low level of education, second/more gestation, weight under 2500 g, Apgar score under 7, premature rupture of membranes, macrosomia and mother's infectious pathology. Accurate identification of risk factors and anticipation at the birth of a high-risk neonate would result in adequate preparation and prompt resuscitation of neonates who need some level of intervention and thus, reducing neonatal morbidity and mortality.

Introduction: Carcinoid heart disease is a rare cause of right-sided valvular dysfunction, an important complication in patients with carcinoid syndrome. Objectives: We aim to present our own experience regarding early myocardial dysfunction in patients with carcinoid syndrome. Methods: 64 patients (35-90 year old, 62,5% female, 37,5% male patients) with carcinoid syndrome were evaluated be-tween October 2017 and June 2021. All patients underwent two-dimensional echocardiography with additional tissue Doppler and speckle-tracking techniques. For all patients there were measured urinary level of 5- hydroxyindolacetic acid, serotonin and NT-proBNP values. Results: The following echocardiographic features: global longitudinal strain of both ventricles, mean systolic velocity of the left ventricle, systolic velocity of the free wall of right ventricle, correlated with high values of specific biomarkers: serotonin, and urinary 5-hydroxyindolacetic acid, and also with the presence of hepatic metastases and poorly differentiated tumors. Discussion: In this study we identified several patients with early myocardial dysfunction due to carcinoid syndrome, representing a predictive model of poor prognosis, requiring further investigations. Conclusion: Echocardiographic assessment based on the measurement of systolic velocities, as well as the global longitudinal strain of both ventricles, together with specific biomarkers may contribute to better recognition of carcinoid heart disease in clinical practice, but this needs validation through further studies enrolling larger number of patients.

Pregnancy is a complex biological process which is associated with significant metabolic and hemodynamic changes of the maternal body which allow a normal fetal growth. The inability to adapt to these changes can affect the cardiovascular health. During pregnancy, women may experience mood swings, anxiety and emotional ambivalence. These symptoms can lead to stress and have a negative impact on the mental well-being of expectant mothers. It is crucial to know the aspects that can influence the development of cardiovascular problems among pregnant women in order to manage these cases properly. The current narrative review explores and summarizes the evidence regarding the impact of stress and anxiety on cardiovascular health in pregnant women. Understanding the physiological adaptations that the body undergoes throughout pregnancy is crucial for educating and supporting individuals as well as healthcare professionals. This enables them to recognize any risk factors or pathological conditions that may exacerbate pregnant women's health. In order to reduce maternal morbidity and mortality from cardiovascular disease, a psychological and cardiovascular risk factor screening that is done either before or during pregnancy may be able to identify situations that call for particular medical and/or psychological therapies.

Synchronous electrical cardioversion is a relatively common procedure in the emergency department (ED), often performed for unstable supraventricular tachycardia (SVT) or unstable ventricular tachycardia (VT). However, it is also used for stable cases resistant to drug therapy, which carry a risk of deterioration. In addition to the inherent risks linked with procedural sedation, there is a possibility of malignant arrhythmias or bradycardia, which could potentially result in cardiac arrest following this procedure. Here, we present a case of complete heart block unresponsive to transcutaneous pacing and positive inotropic and chronotropic drugs for 90 minutes, resulting in multiple cardiac arrests. The repositioning of the transcutaneous cardio-stimulation electrodes, one of them placed in the left latero-sternal position and the other at the level of the apex, led to immediate stabilization of the patient. Extubation of the patient was performed the following day, while full recovery and discharge within 7 days, after insertion of a permanent pacemaker.

Ideas about Artificial Intelligence appeared about half a century ago, but only now is it becoming an essential element of everyday life. The data provided is getting bigger and bigger and, in this case, we need artificial intelligence that helps us with superhuman powers. The interaction with medicine is getting closer and closer, medicine being a field that continues to be perfected. Machine learning, deep learning, neural networks, computer vision are some of the mechanisms that are already applied in medicine, becoming a trend in healthcare worldwide. Artificial intelligence will be the thing that will change contemporary medicine. Developed countries such as Japan, France, Germany have already implemented artificial intelligence in their medical systems. The help is in medical diagnosis, patient monitoring, personalized therapy, and workflow optimization. Artificial intelligence will help surgeons to perfect their skills, to standardize techniques, to choose the best surgical technique. The goal is to predict complications, reduce diagnostic time, diagnose complex pathologies, guide the surgeon intraoperatively and reduce medical errors. We are at the beginning but the potential is enormous.

Objective: This study aimed to demonstrate the availability of portable devices for nasal FeNO measurement, which could replace exhaled NO measurement based on the continuous aspiration of multiple flow measurement systems. Methods: A descriptive cross-sectional study. The healthy subjects without rhinosinusis disorders (control group) and those with diagnosed allergic rhinitis (AR group) were enrolled in the study. They underwent nasal and bronchial FeNO measurements by both fixed flow NObreath® connected to nasal mask and multiple flows HypAir FeNO®. Results: A total of 153 people were recruited including 63 healthy subjects and 90 subjects with AR. There were no statistically significant differences in anthropometric characteristics between the two groups (P > 0.05). There were a significant increase in FeNO values in the AR group compared to the control group; concentrations of nasal and bronchial FeNO mearsured by NObreath® were 76.0 ± 50.7 ppb (vs 36.0 ± 28.1 ppb, P < 0.01) and 32.3 ± 15.4 ppb (vs 9.2 ± 5.6 ppb, P < 0.001), and those mearsured by NObreath® Hypair FeNO® were 1796.9 ± 523.3 ppb (vs 400.2 ± 123.1 ppb, P < 0.001) and 37.3 ± 23.0 ppb (vs 17.4 ± 18.3 ppb, P < 0.01). A weak correlation between the values measured by NObreath® and Hypair FeNO® devices was observed (r = 0.023 and r = 0.089, respectively; p < 0.05). Conclusions: The handheld NObreath® device is effective in measuring FeNO concentrations in both normal subjects and AR patients. The advantages in price and size, creating a compact, low-cost device that is convenient for use and research.

Tumor to stroma ratio is a highly debated prognostic factor in the management of several solid tumors and there is no universal agreement on its practicality. In our study we proposed to confirm or dismiss the hypothesis that a simple measurement of stroma quantity is an easy-to-use and strong prognostic tool. We have included 74 consecutive patients with colorectal cancer who underwent primary curative abdominal surgery. The tumors have been grouped into stroma-poor (stroma &lt;10%), medium-stroma (between 10 and 50%) and stroma-rich (over 50%). The proportion of tumor stroma ranged from 5% to 70% with a median of 25%. Very few, only 6.8% of patients had stroma-rich tumors, 4% stroma-poor tumors and 89.2%tumors with a medium quantity of stroma. The proportion of stroma, at any cut-off, had no statistically significant influence on the disease specific survival. This can be explained by the low proportion of stroma-rich tumors in our patient group and the inverse correlation of stroma proportion with tumor grade. The real-life proportion of stroma-rich tumors and the complex nature of the stroma-tumor interaction has to be further elucidated.

Thromboembolic conditions, such as stroke and myocardial infarction [MI], are the primary causes of mortality globally. High efficiency was demonstrated by fibrinolytic enzymes isolated from microbial sources in dissolving various blood clots. The study aimed to investigate and produce bacterial fibrinolytic enzymes from various Egyptian soil conditions using recombinant DNA technology. Fifty soil samples were examined to determine the production of fibrinolytic enzymes. The plasmin plate technique assessed the thrombolytic activities of the strong fibrinolytic enzyme-producing bacterial isolates. In addition to determining the molecular mass using a mass spectrometer and the western blot method, the activity and thermostability of the enzymes were characterized. An affinity chromatography approach was used to purify the fibrinolytic enzymes. However, bacterial recombinant DNA technology produced the pure bacterial fibrinolytic enzyme. Several dosage formulations for the formulation of fibrinolytic enzymes were tested. By using affinity chromatography and the SDS-PAGE test, the isolated bacterial fibrinolytic enzyme in this investigation was almost 83% pure. Bacillus cereus ATCC 4342 was identified as the predominant bacterial isolate secreting fibrinolytic enzymes. It was discovered that the fibrinolytic enzyme activity of fifty soil samples ranged from 0.167 U/ml to 1.853 U/ml. The extracellular enzyme extracted from Bacillus cereus culture supernatant demonstrated a relatively stable fibrinolytic activity over 18 hours at a pH range of 7.4–10, as well as stability with maximum productivity at 43℃ for over 60 minutes. In this investigation, the enzyme was referred to as Fibrin-proteinase[ FP]. The fibrin clots were directly thrombolyzed by the FP. The calculated values for the specific activity and molecular mass of the FP were approximately 40.71 units/mg of protein and approximately 30 KDa, respectively. It was observed that the presence of Fe+3 marginally boosted protease activity, but the presence of EDTA decreased it. On the other hand, adding monovalent cations like K+1 and Na+1 significantly increased the fibrinolytic activity of FP. The enzyme exhibited activity throughout the temperature range of 20 to 65℃, peaking at 55℃. The ideal range for the generation of protease was 35–43℃ and 8.0–10. The thermostable fibrinolytic enzyme FP, which was isolated from Bacillus cereus ATCC 4342 in various soil environments in Egypt during the current study, was a promising fibrinolytic enzyme because it demonstrated a more extensive and effective fibrinolytic activity and fewer side effects than the fibrinolytic enzymes that are currently available worldwide. It is advised that further research be done on optimizing the right formulation of bacterial fibrinolytic enzymes in the future to help dissolve different types of blood clots and, as a result, lower the high death rate that exists worldwide.

Background: By 2025, road traffic injuries are projected to rank third in the global burden of disease, posing a significant challenge that affects health, social well-being, and economic aspects. According to data from the Romanian Police National Statistics Center, there has been an average of 342 traffic accidents per year involving pediatric patients over the past 10 years. Materials and Methods: A retrospective research study was conducted, encompassing 358 cases of road traffic accidents identified for the study. Data collection was conducted at "St. Mary’s" Emergency Hospital for Children in Iasi, Romania, from January 2015 to December 2022. To facilitate statistical analyses, participants were categorized into three specific age groups, correlating between the anatomical region affected and different types of accidents was examined, and the classification of injury types was determined based on the characteristics of the harm inflicted. Results: An oscillating trend is observed from 2015 to 2020, with its lowest value recorded in 2017 at around 6.8% and its peak in 2019 at 20.1%. Notably, post-pandemic (Covid-19), the cases underwent a substantial decline of approximately 50%. At least 78.7% of those who did not undergo orthopedic reduction required surgery, whereas among those who underwent orthopedic reduction, only 23.4% needed surgery. Regarding the frequency of complications 7,9% of the total cases experienced complications. Conclusion: The increased frequency of pediatric traffic accidents is attributed to the extensive services provided by "St. Mary’s" Emergency Hospital for Children, Iasi, to a significant number of patients from both rural and urban areas across the seven counties of the Moldova, Romania.

Lynch syndrome (LS) is one of the most common hereditary cancer syndrome in human populations, associated with germline variants in MLH1, MSH2/EPCAM, MSH6 and PMS2 genes. The advent of next generation sequencing has proven a significant impact in germline variant detection in the causative genes; however, a large proportion of patients with clinical criteria still receive uncertain or negative results. PMS2 is the least frequent reported gene, associated with up to 15% of LS cases with late-onset disease and low penetrance phenotype; however, the proportion of PMS2-LS cases is considered to be highly underestimated. In this context, we consulted public available databases (ClinVar, LOVD) for missense and intronic PMS2 variants and performed an in silico analysis of the genomic sequence. Splicing bioinformatics tools proven effective in other genes were used to assess both the wild-type DNA sequence and reported genetic variants. Splicing alterations were predicted in silico and using GTEx short-read RNA expression data. Out of the 2384 missense variants discovered, 90% were classified with uncertain significance (VUS). 4.9% of missense variants were shown to have a potential splicing consequence (DS &gt; 0.2) using SpliceAI. As described in the original publication, SpliceAI-visual was proven effective in annotation of short intronic variants (&lt; 50 bp). Four short intronic variants were identified using SpliceAI-visual as potentially splicing disturbing, in spite of using a lower threshold (DS &gt; 0.1). Moreover, we observed that Splicing Regulatory Elements (SREs) may play a fundamental role in alternative splicing in PMS2 gene, ESE motifs being overrepresented in highly expressed exons 5, 11 and 14. Computational analysis performed in our study serves as a valuable filtering step for guiding further RNA sequencing experiments. Additional functional data is necessary to evaluate the significance of our findings.

The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. We have now investigated all bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies with minodronate could be valuable.

In this article, we analyze the relationships that connect graduates from high school, the training system and employment rates and conditions in the Italian regions between 2004 and 2022. The data used refer to the Istat Bes database. The results show that the growth in the number of high school graduates is positively associated with higher university education and employment with the exception of job satisfaction. Subsequently we also present a clusterization with k-Means algorithm confronting the Silhouette Coefficient with the Elbow Method. Finally, we confront seven different machine-learning algorithms for the prediction of the level of graduated from high school. We also present economic policy suggestions to increase schooling in the Italian regions. The results are critically discussed.

This research addresses a gap in the literature by conducting a comprehensive analysis of patients’ level of satisfaction with dental care. Methods: By combining quantitative and qualitative survey methods with the PSQ questionnaire this study aims to augment ongoing initiatives to enhance dental patients’ experiences by painting a more comprehensive depiction of patients' level of satisfaction; Results: When asked about their overall level of satisfaction 77,1% of the patients said they received excellent services from the office personnel and 72,2% said they trust their doctors; Conclusions: Assessing patient satisfaction in the realm of dental services quality is crucial for enhancing service quality and accuracy, benefiting both patients and dentists, and ultimately improving public health.

Congenital heart disease (CHD) is a prevalent congenital disorder diagnosed with high frequency, affecting approximately 0.8% to 1.2% of all live births. Research has demonstrated that the use of pulse oximetry and clinical examination as a screening tool for CHD diagnosis has proven extremely valuable. We conducted a retrospective longitudinal study over a 3-year period that involved screening 1188 newborns admitted to the NICU during the first 72 hours of life within this timeframe. 201 newborns were diagnosed with CHD. Almost all (n=198) had a positive screening test during the 72-hour period, while 3 had a negative screening test, but were later diagnosed using echocardiography. The prevalence rate was 16.67%. A confusion matrix was constructed with 198 true positives (TP), 3 false negatives (FN), no false positives (FP), and 987 true negatives (TN). The sensitivity of the screening test was 98.51%, while the specificity 100%, with no false positives. In our study, a total of 9 deaths occurred. Using the Kaplan-Meier method, the survival probability appeared to be slightly above 0.9 (95.5%), indicating that almost all patients survived past 72 hours after being diagnosed with CHD. Pulse oximetry is an effective, low cost and easy-to-use method and a useful tool to assess and lead to the diagnosis of CHD.

Heart failure is a global major healthcare problem with millions of hospitalizations annually and with a very high mortality. There is an increased interest in finding new and reliable biomarkers for the diagnostication, prognostication and therapeutical guidance of patients hospitalized for acute heart failure. There is data to sustain the role of CA 125, a worldwide used marker of ovarian cancer, in patients with heart failure. Several studies have shown links between CA 125 levels and congestion seen in acute heart failure, high mortality and readmission rates at 6 months follow up after discharge from acute heart failure and also a role of CA 125 in the guidance of heart failure therapy. There are also clinical trials that showed that several particularities of CA 125 make it even better than NTpro BNP ( a classical and more utilised marker of heart failure) in several scenarios of acute heart failure.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

BACKGROUND: Thromboembolic disorders including Myocardial infarction[ MI] and stroke represent the leading causes of death worldwide. Fibrinolytic enzymes extracted from microbial sources showed high efficacy in the dissolution of different blood clots. AIM OF THE STUDY: Screening and the bacterial recombinant DNA manufacture of bacterial fibrinolytic enzymes from different soil environments in Egypt. METHODOLOGY: A total of 50 soil samples were screened for their fibrinolytic enzyme production. The potent fibrinolytic enzyme-producing bacterial isolates were evaluated for their thrombolytic activities using the plasma plate method. The characterization of the enzyme activity and thermostability were carried out; also, the determination of molecular mass using a mass spectrometer and western blot technique was performed. The purification of the fibrinolytic enzymes was done through the affinity chromatography technique. On the other hand, the production of the purified bacterial fibrinolytic enzyme was achieved via bacterial recombinant DNA technology. Formulation of fibrinolytic enzymes in different dosage forms was tried. RESULTS: In the present study, the purified bacterial fibrinolytic enzyme was approximately 83% pure through affinity chromatography and SDS-PAGE assay. The predominating bacterial isolate secreting fibrinolytic enzymes was found to be Bacillus cereus. The fibrinolytic enzyme activities of 50 soil samples were found to be in the range of 0.167-1.853 U/ ml. The fibrinolytic activity of the extracellular enzyme refined from the culture supernatant of Bacillus cereus was relatively stable over the PH range from 7.4-10 for 18 hours and also it showed stability with the highest productivity at a temperature of 43 0C for nearly 60 minutes. The enzyme was called fibrin-proteinase[ FP] in the present study. The FP degraded the fibrin clots via direct thrombolysis. The specific activity and the molecular mass of the FP were estimated to be nearly 40.71 Units/ mg protein and nearly 30 KDa respectively. Protease activity was noticed to be slightly increased in the presence of Fe+3; While it was inhibited in the presence of EDTA. On the other hand, the FP fibrinolytic activity was enhanced greatly after the addition of monovalent cations such as K+1 and Na +1. The enzyme was also active over the temperature range of 20- 65 0C with the highest activity at 55 0C. The optimum temperature and PH of protease production was at 35-43 0C and PH 8.0-10. Conclusion: During the present study, the thermostable fibrinolytic enzyme FP purified from Bacillus cereus in different soil environments in Egypt was a promising fibrinolytic enzyme because it showed a broader efficacious fibrinolytic activity as well as less adverse effects than the current fibrinolytic enzymes globally. It is recommended in the future advanced exploration of the optimization of suitable formulation of bacterial fibrinolytic enzymes to aid in the dissolution of various blood clots and as a consequence overcoming the high rate of mortality globally.

Landiolol is an ultra-short-acting, selective ß1- adrenergic receptor blocker that was originally approved by Japan for the treatment of intraoperative tachyarrhythmias. It has gained attention for its use in the management of tachyarrhythmias and perioperative tachycardia, especially atrial fibrillation for both cardiac and non-cardiac surgeries. It can be the ideal agent for heart rate control due to its high β1‐selectivity, the potent negative chronotropic effect, a limited negative inotropic potential, and an ultrashort elimination half‐life (around 4 min); moreover, it may have a potential therapeutic effect for sepsis and pediatric patients. Landiolol seems to be superior to other short‐acting and selective beta‐blockers such as esmolol. This review aims to provide a comprehensive overview of landiolol, a new ultra-short-acting ß1 selective antagonist, including its pharmacology, clinical applications, efficacy, safety profile, and future directions in research and clinical data.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C&gt;T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

This paper explores the transformative impact of computational pharmaceutics, integrating AI, multi-scale modeling, quantum computing, AI-driven drug discovery, and blockchain frameworks. Molecular dynamics simulations provide insights into atomic behaviors crucial for drug design. Quantum computing reduces computational costs for simulating protein-drug interactions. AI and Graph Neural Networks accelerate drug discovery and personalized medicine. Blockchain frameworks facilitate secure pharmacogenetic data sharing. These advancements revolutionize drug development, offering unprecedented efficiency, innovation, and personalized treatments.

Introduction: Birth Asphyxia is a severe condition that includes many potential pathways of occurrence both in utero and during childbirth. We aimed to identify and describe specific macroscopic and microscopic placental injuries in birth asphyxia to serve as a quick tool to stratify a newborn’s potential further evolution, as hypoxic-ischemic encephalopathy can be responsible for neonatal death or severe neurologic sequelae further compromising the affected persons’ quality of life. Materials and methods: We conducted an observational prospective study over 3 years. 62 patients diagnosed with birth asphyxia which had placental histopathological examination performed were enrolled. The control group consisted of 69 term newborns that required neonatal intensive care for at least three days, in the same period, for any other reason and that also had available placental exams. In our study, placental histopathological lesions identified in birth asphyxia have been classified according to Amsterdam Criteria. Results: We analysed data gathered from both groups by applying specific statistical tests for each type of variable and hypothesis. Thus, umbilical cord abnormalities were associated with hypoxic-ischemic encephalopathy in a statistically significant manner when comparing the birth asphyxia group of newborns with the control group. Also, we identified a high statistical level of significance for maternal and fetal vascular malperfusion and the occurrence of hypoxic-ischemic syndrome when comparing the two groups (p = .00). Conclusion: The macroscopic and microscopic placental examination can provide important information on the evolution of the disease in selected newborns according to the identified lesions.

Background: Antibiotic resistance is an overwhelming serious difficulty globally. This necessitates the exploration of novel sources of antibiotics to overcome this challenge. Aim of the study: Bacterial Myxopyronin A production from various soil environments Egypt; as well as testing its antimicrobial activity in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Different soil environments in Egypt were screened for the growth of bacterial isolates producing Myxopyronin A as an antimicrobial agent. Purification of Myxopyronin A was performed via reversed-phase HPLC. Paper disc diffusion assay, as well as the Broth dilution technique, were exploited to assess the invitro antimicrobial and minimum inhibitory concentration( MIC) of the test antibiotic. Furthermore, in vivo antimicrobial spectrum, adverse drug reactions, and pharmacokinetics were detected during animal model testing stages and human randomized clinical trials phases 1/2. Results: From the culture supernatant of the Myxobacterium Myxococcus fulvus 124B02 which was the predominant soil bacterial isolate grown on the Casein yeast peptone plate, Myxopyronin A was produced. The test antibiotic blocked the growth of many Gram +ve bacteria with MICs less than 100 mcg/ ml. In contrast, it inhibited the growth of a few Gram -ve bacteria such as Escherichia coli at MICs greater than 100 mcg/ ml. On the other hand, Eukaryotic cells such as fungal and human cells were not affected. Prokaryotic DNA-dependant-RNA polymerase( RNLP) was noticed to be inhibited via the test antibiotic suggesting its bactericidal action. The maximum concentration was 7-8 mcg/ ml at a maximum time of 2 hours when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.5 hours following first-order kinetics of elimination. The duration of its action was nearly 12 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and cholestatic jaundice in less than 5 % of experimental candidates. Conclusion: The present study was promising due to the bactericidal antibiotic Myxopyronin A production from Myxococcus fulvus 124B02 isolated from different soil environments in Egypt.

Background and Objectives: High job strain is worsening the outcome in coronary artery disease, CAD. Severe dissatisfaction on workplace, imbalance between high demands , and low rewards, are affecting the quality of life, and diminishing the duration of life, especially in CAD patients. Our study included two samples : CAD patients (experimental group), and without CAD patients, but with traditional risk factors (control group). The main objective of the study was the role played by high sensitivity C reactive protein, hs CRP, and microalbuminuria, as mediators of job strain and CAD relationship. Secondary objectives were the following: identification of the most vulnerable patients( with significant job strain) and intervention towards this category, for cardiovascular events prevention (primary or secondary). Materials and Methods: The utilized methods were the following : clinical exam; electrocardiogram; echocardiogram; non contrast enhanced computed chest tomography; laboratory findings ( lipid profile, glycemia, hs CRP, microalbuminuria); type D scale, DS 14; depression questionnaire, PHQ-9; and satisfaction with work scale, SWWS. Results: The highest values for hs CRP and microalbuminuria were noticed in patients with the lowest Likert score, for both samples CAD, and without CAD patients. The highest job strain was noticed in females. More than half of CAD patients ,with low Likert scores, revealed myocardial infarction. Conclusions: Microalbuminuria and hs CRP were statistical significant in the study as intercessors, in job strain and CAD relationship. The most vulnerable patients for vascular events were females, in both groups : CAD and “CAD waiting desk”. In CAD sample, the vascular vulnerability was also increased by high job strain.

Much research has been conducted to determine how hair regeneration is regulated, as this could provide therapeutic, cosmetic, and even psychological interventions for hair loss. The current study focused on the hair growth effect and effective utilization of fatty oil obtained from Bryde's whales through high-throughput DNA microarray approach in conjunction with immunohistochemical observations. The research also examined the mechanisms and factors involved in hair growth. In an experiment using female C57BL/6J mice, the vehicle control group (VC: propylene glycol: ethanol: water), the positive control group (MXD: 3% minoxidil), and the experimental group (WO: 20% Whale Oil) were topically applied to the back of the mouse. The results showed that 3% MXD and 20% WO were more effective than VC in promoting hair growth, especially 20% WO. Furthermore, in hematoxylin and eosin-stained skin tissue, an increase in the number of hair follicles and subcutaneous tissue thickness was observed with 20% WO. Whole-genome transcriptomic analysis also showed that 20% WO may have lower stress- and inflammation-related responses than 3% MXD. Therefore, whale oil can be expected to be used as a safe hair growth agent.

In spite of prevalence gaps in several micronutrients supporting immune function, significance of their deficits/supplementation for efficacy of vaccines is underinvestigated. Thus, influence of supplementation combining vitamins C and D, zinc, selenium and manganese, and N-acetyl-cysteine on mouse IgG responses and underlying mechanisms to seasonal quadrivalent influenza vaccine (QIV) was investigated. QIV was given in two doses (28 days apart). The supplementation starting 5 days before the first injection increased the total serum IgG titre, through stimulation of germinal centre (GC) reaction in secondary lymphoid organs (SLOs), as indicated by increase in the frequency of GC B cells and follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells. Additionally, the supplementation “optimized” IgG response following the second QIV injection by supporting more favorable (in respect to virus clearance) IgG2a response through favoring Th1 differentiation as indicating by Th1 (INF-γ) /Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely reflected partly their antioxidant action (as indicated by redox status analyses) on Th cell differentiation. Thus, the study forms solid base for further research aimed at repurposing use this safe and inexpensive micronutrient combination as an adjuvant for virus influenza vaccine.

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

Background: RSV, or respiratory syncytial virus, is a deadly condition that is present all over the world today. The infection is initially contained in the lower respiratory tract without systemic transmission. The objective of the study: Bioinformatics was used in Egypt to create an mRNA vaccine against the Respiratory syncytial virus (RSV). Methodology: In the present screening experimental study, a lipid nanoparticles vaccine of mRNA of the surface fusion protein of Respiratory syncytial virus was manufactured. The present vaccine delivery system was lipid nanoparticles with a particle size of approximately 90 nanometres, manufactured by the hot micro-emulsion method. In stages 1 and 2 of clinical trials, the immunogenicity of the current mRNA RSV vaccine was evaluated. Results: The current vaccine demonstrated 81% immunogenicity in animal testing, but only 69% in stages 1 and 2 of clinical trials. Its side effects were manageable. The results persisted for a while. In the current trial, the vaccination proved effective as a preventative measure against RSV infection. The current vaccination lacked antibody-dependent enhancement, which causes non-protective antibodies to develop. These non-neutralizing antibodies exacerbate infection by activating cytokines and complement cascade through the formation of immune complexes or enhancement of the virus entry and replication in the host cells. On the other hand, the current RSV mRNA vaccine of the surface fusion protein consequent on the production of powerful neutralizing antibodies with prolonged immunity especially to infants and elderly candidates who received the optimal dosage regimen.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (&gt;12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

The review explores the therapeutic potential of mangrove plants as sources of bioactive compounds, particularly focusing on their anti-inflammatory properties. Mangroves, found in tropical and sub-tropical tidal coasts, exhibit unique ecological and biological activities. The review compiles and examines 136 research findings published between 1982 and 2018, with 41 studies specifically addressing the anti-inflammatory properties of mangroves in Indian coastal regions, including the Andaman and Nicobar Islands. It summarizes the chemical structures, molecular weights, formulas, solvents, and biological activities of these mangroves, as reported by various researchers over time. The data underscore the significant potential of tropical Indian mangroves in anti-inflammatory applications. However, a notable research gap exists regarding the extraction of bioactive compounds from mangrove species in the Andaman and Nicobar Islands compared to other regions such as Gujarat, Maharashtra, Goa, Karnataka, Kerala, Tamil Nadu, Andhra Pradesh, Odisha, West Bengal, and Puducherry. Overall, the compilation provides valuable insights into mangrove-based studies for drug discovery research, emphasizing the need for further exploration and exploitation of these natural resources.

Background and Objectives: Wilson disease (WD) is a disorder of copper metabolism caused by genetic muta-tions in the ATP7B gene which lead to the accumulation of copper in the body. The aim of the present study is to investigate the severity of WD in patients in Romania. Materials and Methods: This study was conducted us-ing an online questionnaire consisting of 32 questions in a group of patients suffering from Wilson disease. Results: The study included 67 people aged 7 to 56 with WD. The most common symptoms of the participants were hepatic and neurological in 22 cases (32.8%). The most common neurological symptom in the assessed cases was muscle stiffness (49.5%), followed by tremor (45%), and speech disorders (40.5%). The Kay-ser-Fleischer ring was present in 50.7% of the participants. The most commonly used drug treatment in the participants was D-penicillamine (77.61%). Conclusions: The severity of WD is based on many aspects, the most important being early diagnosis and access to treatment throughout the year. The prognosis is favorable with early diagnosis and treatment, but it is crucial to diagnose individuals before they develop major symp-toms. Therefore, advances in WD screening can lead to an earlier diagnosis and better results.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding children are scarce. The purpose of our study is to explore the risk factor for AKD and impact of AKD following an acute kidney injury (AKI) episode in children on mortality and new-onset CKD. Methods: We retrospectively evaluated 736 children with ages between 2 and 18 years old with AKI admitted in a tertiary care hospital from the west Romania over a 9 years period. Results: AKD incidence following AKI was 17%. Patients that developed AKD were older, with higher baseline serum creatinine values, urea, C reactive protein and lower proteins, haemoglobin and sodium. They were more often exposed to sepsis, critical illness and nephrotoxic medications and presented certain susceptibilities like CKD, neoplasia, anemia, heart failure, arterial hypertension, stem cell transplant and female gender. AKI causes that increased the risk of AKD were intrinsic ones. AKD increased the overall mortality by three times. The factors that independently increased the risk of evolution towards CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: AKD is an independent risk factor for mortality and new-onset CKD in children.

Hypertension is a frequent risk factor for cardiovascular diseases and the prevalence rate is continuously rising. Multiple pathophysiological mechanisms are responsible for hypertension, necessitating a combination of drugs from different classes for best management. Combination therapy is five times more effective in decreasing blood pressure compared to escalating the dose of a single agent. As per the ACCOMPLISH trial analysis, coupling a renin-angiotensin system inhibitor with a calcium channel blocker is more effective than the combination of a renin-angiotensin system inhibitor with diuretics in reducing major cardiovascular events, cardiovascular-related mortality, and the progression of chronic kidney disease. The renin-angiotensin system can be suppressed by inhibiting the angiotensin-converting enzyme or angiotensin type 1 receptor (AT1R), resulting, in decreased vascular smooth muscle contraction, heart performance, and reduced aldosterone synthesis. Calcium channel blockers work by inhibiting L-type calcium channels, reducing heart performance via negative inotropic, chronotropic, and bathmotropic effects, along with reducing vascular smooth muscle contraction. Diuretics exert their antihypertensive impact by changing body fluid volume and electrolytes. Initially, hypertension treatment commences with a single medication but often, different classes of two or more antihypertensive medications are necessary for achieving the target blood pressure goal. Sometimes, for Resistant hypertension four different classes of antihypertensive medications are necessary to reach the target blood pressure goal.

Background/Objectives: Concurrent opioid (OPI) and benzodiazepine (BZD) use may exacerbate falls/fractures risk compared to no use or use alone. Yet, patients may need concurrent OPI-BZD use for co-occurring conditions (e.g., pain and anxiety). Therefore, we examined the association between longitudinal OPI-BZD dosing patterns and subsequent injurious falls risk. Methods: We conducted a retrospective cohort study including non-cancer fee-for-service Medicare beneficiaries initiating OPI and/or BZD in 2016-2018. We identified OPI-BZD use patterns during the 3 months following OPI and/or BZD initiation (i.e., trajectory period) using group-based multi-trajectory models. We estimated time to first injurious fall within 3 months post-trajectory period using inverse-probability-of-treatment-weighted Cox proportional hazards models. Results: Among 622,588 beneficiaries (age≥65=84.6%, female=58.1%, White=82.7%; having injurious falls=0.45%), we identified 13 distinct OPI-BZD trajectories: Group(A):Very-low OPI-only (early discontinuation)(44.9% of the cohort); (B):Low OPI-only (rapid decline)(15.1%); (C):Very-low OPI-only (late discontinuation)(7.7%); (D):Low OPI-only (gradual decline)(4.0%); (E):Moderate OPI-only (rapid decline)(2.3%); (F):Very-low BZD-only (late discontinuation)(11.5%); (G):Low BZD-only (rapid decline)(4.5%); (H):Low BZD-only (stable) (3.1%); (I):Moderate BZD-only (gradual decline)(2.1%); (J):Very-low OPI (rapid decline)/Very-low BZD (late discontinuation)(2.9%); (K):Very-low OPI (rapid decline)/Very-low BZD (increasing)(0.9%); (L):Very-low OPI (stable)/Low BZD (stable)(0.6%); and (M):Low OPI (gradual decline)/Low BZD (gradual decline)(0.6%). Compared with Group(A), 6 trajectories had increased 3-month injurious fall risks: (C): HR, 95%CI=1.78, 1.58-2.01; (D): 2.24, 1.93-2.59; (E): 2.60, 2.18-3.09; (H): 2.02, 1.70-2.40; (L): 2.73, 1.98-3.76; and (M): 1.96, 1.32-2.91. Conclusions: Our findings suggest that 3-month injurious fall risk varied across OPI-BZD trajectories, highlighting the importance of considering both dose and duration when assessing fall risks of OPI-BZD use among older adults.

Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline-trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer’s disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected 21 sources referring to 14 studies focused on KarXT, out of which only four have published results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline-trospium are good, but more data is needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs.

Background: Chronic lateral epicondylitis challenges the therapeutical approach; underlying mechanisms are incompletely understood; neuropathic pain and central and peripheral sensitization may explain the fact that botulinum toxin was found to play a role in pain and function management. Methods: We searched the literature for MeSH terms: lateral epicondylitis or synonyms and botulinum toxin. Results: We found 14 papers containing trials on botulinum toxin injection into the tendon or into the extensor muscles (particularly extensor carpi radialis brevis and extensor communis digitorum). We followed the administration pathways, doses, timing and side effects. Conclusion: With chronic course, the focus of the therapy shifts from the afflicted tendon to the inserting muscles, as muscle contracture may create a vicious loop to perpetuate and aggravate the disease. Doses, timing and side effects are discussed.

Injury to the peritoneum during surgery is followed by a healing process that frequently results in the attachment of adjacent organs by a fibrous mass, referred to commonly as adhesions. Because injuries to the peritoneum during surgery are inevitable, one must understand the mechanisms of adhesion formation to prevent its occurrence. This requires a thorough understanding of the molecular sequence that results in the attachment of injured peritoneum and the development of fibrous tissue. Recent data show that fibroblasts from the injured peritoneum may play a critical role in forming adhesion tissues. Therefore, identifying changes in gene expression patterns in the peritoneal fibroblasts during the process may provide clues to the mechanisms by which adhesion develops. This review presents many papers discussing genes implied in peritoneal adhesion.

It has been shown that Human papillomavirus (HPV) infection is associated with several forms of cancer. Additionally, although there are more than 100 types of HPV, more than ten types of it, including types 16 and 18, are considered high-risk. The two proteins that make up the viral capsid of HPV 16 are L1, the major capsid protein, and L2, the minor capsid protein. FDA (The Food and Drug Administration) approved HPV vaccines mostly target L1 and L2 capsid proteins, which facilitate intracellular entry during infection. In this study, it was set out to analyze the creation of phylogenetic relations of L1 nucleic acid sequences of viral isolates. This study also analyzed sequences of three key elements within the amino acid sequences of HPV 16 L1: loops critical for structural stability, nuclear localization signal sequences, and residues implicated in viral attachment. As highlighted by the literature, these elements represent pivotal aspects of viral function. Furthermore, the report highlighted the particular inter-sequence variability within the HPV 16 L1 protein sequences. Overall analysis revealed clustering of sequences primarily due to geographical and characterized by more phylogenetic relatedness within location-specific clusters.

According to Indonesia’s result of Basic Health Research of 2013, prevalence of acute respiratory infection in 2007 and 2013 were not different (25.5% and 25.0%, respectively). Identifying the cause of acute pharyngitis is a key point in determining the optimal treatment. The main purpose is to evaluate the rational use of drugs and its irrational impact as well as the correlation of the drug use with the incidence and prevalence of acute pharyngitis. This study was a descriptive and observational study, carried out retrospectively and concurrently at two community health centers located in Bandung and Cimahi, Indonesia. There were 80.01% over prescription of antibiotics, with a total of 8.98% is non-treatment option, and 62.43% irrational used of corticosteroids. The incidence and prevalence of acute pharyngitis at one health center in Bandung were 2.45% and 2.31%, respectively, with irrationality rate of 83.82%. Those recorded at one health center in Cimahi were 2.11% of incidence and 2.00% of prevalence with irrational rate of 91.29%. It can be concluded that there were still irrational use of medicines in the treatment of acute pharyngitis in community health center. The higher incidence and prevalence might indicate the declining health services quality.

The release of the active substance from the matrix modified-release tablets based on Kollidon®SR and chitosan depends on its solubility in the dissolution medium and on the composition of the matrix-forming polymers. The study is based on new oral matrix tablets based on Kollidon®SR and chitosan, formulated to optimize the low oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug, a class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method, and their combination at 1:1, 1:2, 1:3 chlorzoxazone/ excipients, 20%-40% (w/w) Kollidon®SR, 3-7% (w/w) chitosan and the auxiliary substances were formulated in constant concentrations. Pharmaco-technical characterization included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, Carr Index), and of pharmaco-chemical characteristics (mass and dose uniformity, thickness, diameter, mechanical strength, Friability, degree of softening, in vitro release profile) of the tablets. Based on the initial evaluation of the pharmaco-technical analysis, pharmaco-chemical characteristics, and in vitro release profile, only three matrix tablet formulations (F1b, F2b, and F3b) were further tested. They were evaluated through Fourier-transform infrared spectrometry, X-ray Diffraction, thermogravimetry, differential scanning calorimetry, and in vitro dissolution tests. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified release oral formulations. In vitro kinetic study reveals a complex mechanism of release occurring in the first (0 - 2 hours) and second (2.0 hours – 36 hours) steps of drug release. Two factors have been calculated to assess the release profile of chlorzoxazone: f1 - the similarity factor and f2 - the factor difference. The results have shown that both Kollidon®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. In vitro dissolution tests revealed the F2b sample, data suggesting a faster drug release. The three formulations showed optimum pharmaco-technical properties and in vitro kinetic study, and they had tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone.

Background: Annual influenza epidemics are a serious public health problem, causing particularly severe morbidity and mortality in high-risk groups. The study aimed to understand Poles' attitudes and beliefs towards influenza vaccinations in the flu season of 2022–2023, analyze preferences and unmet needs regarding influenza vaccinations, and examine the perception and acceptance of the influenza vaccine among individuals at risk of flu complications. Methods: A cross-sectional survey-based study was carried out on a sample of 1446 respondents. The Google Forms questionnaire was created and disseminated electronically using social media and e-mail. The pre-test was performed at the beginning of the project. Results: The majority of respondents (71%) could identify "high-risk groups" recommended for influenza vaccination. Furthermore, it was observed that individuals aged 21 to 59 demonstrated a higher level of knowledge in this regard compared to those below 20 and above 65 years old, and individuals with higher and medium education levels were much better at identifying risk groups for influenza virus infection. The majority of respondents (52.01%) reported receiving influenza vaccination at some point in the past, with 32.12% receiving it in the 2022–2023 flu season and 41.09% in the 2021–2022 season. The majority of respondents declaring acceptance of the vaccine for the 2022-2023 season were in the high-risk group. Only 17.28% of respondents declared receiving both influenza and SARS-CoV-2 vaccines in the 2022-2023 season, with the vast majority being respondents from the "high-risk group" (p

Meningitis is a severe disease associated with death in children under five with highest rates of infections under age of one. Vaccines for Neisseria meningitides and Haemophilus influenza are used to prevent the main causative agents of meningitis. Administration of H. influenzae type b (Hib) vaccine is recommended at 2, 4 and 6 months with a booster dose at 18 months. N. meningitidis has two commercially available vaccines, the pure polysaccharide is recommended at 24 months meanwhile the protein-conjugated vaccines at 12 months. We sought in this study to examine if coadministering the vaccines for the two main meningitis causing bacteria might be synergistic as a preliminary step towards the possibility of shuffling immunization schedule. So, we coadministered Hib vaccine with commercially available vaccines either quadrate (ACWY) polysaccharide meningococcal (Men) or conjugated meningococcal (Nim) vaccines in Balb/C mice (n = 6/group) and compared to each vaccine administered separately and controls. Thirty-five days post immunization, we measured specific antibodies titers. Hib vaccine increased Men antibody titers significantly for serotypes Y and W. When Hib vaccine was coadministrated with Nim, antibody titer for Y, W and A significantly increased. For serotype C, there was no significant difference in antibody titers among immunized groups. As for effect of meningococcal vaccines on Hib, Men significantly increased Hib antibody titers while Nim had no effect. Collectively, our data suggested that coadministration of Hib and Men or Nim vaccines was safe and had synergistic effect on immune responses elicited to both vaccines. Further studies are needed before immunization schedule modifications. Such immunization schedule recommendation should provide better protection against this life-threatening disease in young children.

Pharmacy personnel often answer telephones to respond to pharmacy customers (subjects) who received messages from automated systems. This research examines the communication process in terms of how users interact and engage with pharmacies after receiving automated messages. No study has directly addressed automated telephone calls and subjects’ interactions. The purpose of this study is to test the interpersonal communication (IC) process of uncertainty in subjects in receipt of automated telephone calls from pharmacies. Subjects completed a survey of validated scales for Satisfaction (S); Relevance (R); Quality (Q); Need for Cognitive Closure (NFC). Relationships between S, R, Q, NFC, and subject preference to an automated telephone call (ATC) were analyzed to determine whether subjects contacting pharmacies display information seeking behavior. This research demonstrates that seeking information occurs if subjects: are dissatisfied with the content of the ATC; perceive that the Q of the ATC is high; perceive that the Q of ATC is high, and like receiving the ATC or with high NFC, and do not like receiving ATCs. Other interactions presented complexities amongst uncertainty and tolerance of NFC within the IC process.

The understanding of the issues that affect the training of information professionals requires reflection on the impact of Digital Information and Communication Technologies in the current working world, characterized by the rupture of the notion of space / time and the crossing of jurisdictions and professional boundaries, where dilemmas pedagogies to qualify these professionals considering future perspectives. It was based on the assumption that "studies of graduates" are subsidies for the evaluation of the educational system in face of the demands of in the labor market, helping in the progression of the researches in information, education and work. The objective was to map the results obtained in the studies of graduates promoted in the postgraduate and undergraduate courses in Information Science and Librarianship to verify if the demands pointed out in the surveys with graduates are in line with the studies of Education and Training, the orientations of the National Curricular Guidelines (DCN) and the regulatory actions of the Federal Library Board (CFB). The sample consisted of 45 studies published in CI journals on their associated areas, in the Brazilian context, from 2000 to 2018, of which only 10 articles related to the Library Sciences were considered for the qualitative analysis of this initial phase. to enable a comparative analysis between the proposals of the DCN, the critical analysis of the academic area of ​​CI in the studies on education and professional formation (pedagogical projects and curricula) and the orientations of the class councils. The results were categorized according to the reflection of the graduates about their education, the experience of education, vision about professional practice and the labor market; and followed the structure of the DCN axes: profile; skills and abilities; curricular contents, internships and complementary activities; course structure and institutional evaluation. Prevalence of studies on the identification of graduates (gender, age group, employment and work place) was predominant; few focused on salary aspects; and there were no questions about cultural habits or perceptions about changes in the world of work. Results on issues related to job placement and employability have indicated the need to expand the range of possibilities that go beyond traditional information units and the importance of internships for understanding new virtual work spaces. The dimension of the academic formation was evaluated questioning the compatibility of the disciplines with the demands of the labor market and the satisfaction of the graduates with the course and profession, being indicated as more important contents for the professional life the more technical disciplines and that characterize the course of Librarianship, complemented by those related to management; and with less relevance to the language subjects; marketing; statistic; information and information technology, as opposed to the flexibility proposed by the DCN, adopted after 2002. It is concluded that the process has been guided by isolated initiatives, and that the collective debate involving university and the professional world lacks actions for the construction of dialogue, which may result in the definition of pedagogical and curricular projects suited to the demands of graduates in their regions of origin and demands of the world of work.

Chronic kidney disease patients treated by hemodialysis present a high cardio-vascular morbidity and mortality. There is an imperative need for novel biomarkers in identifying and to offer possible therapeutically intervention in these patients. We performed a prospective observational cohort study on 77 patients in the period October 2021 – October 2023. We measured serum plasma levels of Interleukin 1-Beta, Galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. Mean age was 61.02 (±11.81) years, 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4-7.8) years. Median ejection fraction was 51 (43-54 %) and more than two thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-Beta correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle tele systolic diameter. Galectin 3 values negatively correlated with aortic valve fibrosis and mitral valve calcifications and human suppression tumorigenity factor 2 negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better asses the cardio-vascular disease in patients on maintenance hemodialysis.

Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with LPS-induced ALI in mice and to investigate its possible mechanism of action. The experimental results showed that the administration of SS-1 could inhibit LPS-induced inflammation. SS-1 could reduce the number of inflammatory cells, inhibit MPO activity, regulate the TLR4/PI3K/Akt/mTOR pathway and the signal transduction of NF-κB and MAPK pathways in the lung tissue, and inhibit HNGB1 activity in BALF. In addition, SS-1 could affect the synthesis of antioxidant enzymes HO-1 and Trx-1 in the lung tissue and regulate signal transduction in the KAP1/Nrf2/Keap1 pathway. Histological results showed that administration of SS-1 prior to induction could inhibit the large-scale LPS-induced neutrophil infiltration of the lung tissue. Therefore, based on all experimental results, we propose that SS-1 exhibits a protective effect against LPS-induced (ALI) in mice. The mycelium of S. sanghuang can potentially be used for the treatment or prevention of inflammation-related diseases

This paper aims to establish a current relationship between pharmaceutical sciences and the development of perfumes and fragrances, which bring significant economic benefits and whose added value is among other professionals, the one made by professionals in Pharmacy. For this purpose, historical data are used as a starting point and galenic, chemical and botanical aspects are discussed in a transversal way. In this sense, it must be taken into account that in the case of Spanish pharmacy, it is closely linked to the knowledge and use of plants. Sources such as Web of Science (WOS) and databases such as Scopus, monographs and various web pages (where scientific-technical documents appear) have been used. The results and discussion are based on the selection of the 50 plant species most commonly used in high quality fragrances. Therefore, this publication should be considered as an approach to this subject based on an analysis of a representative sample of data. Some characteristics of perfumes (classification according to the concentration of essential oils and combination of plant extracts) are presented beforehand. They also briefly compile the traditional and modern ways in the treatment of these extracts. The main focus of this work is the botanical and chemical analysis of these described plants, pointing out their common name, correct botanical name, geographical place of origin, used part of the plant and main molecules. The 50 botanical species belong to 27 families of angiosperms and are represented in a large part of the phylogenetic tree of botanical systematics. The most significant families are aromatic: Rutaceae (16.7%), Lamiaceae (16.7%) and Apiaceae (6.5%). The most represented genus is Citrus (with seven species or hybrids). However, it should be noted that natural extracts of good quality natural fragrances may be supplemented with chemically synthesized molecules. Of the 50 botanical species selected, 84% of the extracts have their origin in Tropical Asia, the Middle East and the Mediterranean region. This figure generally coincides with the percentage of medicinal plants (or their extracts) admitted by the European Pharmacopoeia. All parts of a plant (depending on which one it is) can be a source of molecules for the elaboration of these products. The most commonly used parts to obtain extracts are flowers (34%) and leaves (30%), a biological circumstance that is explained in this work. On the opposite side are the resins (10%), rhizomes and roots (8%). In this work, 110 molecules have been found that are part of the essences of perfumes and fragrances, the most frequent are: linalool, limonene, 1,8-cineole, eugenol and derivatives, geraniol, vanillin and derivatives, β-cariophyllene, p-cmene and farnesene and derivatives (3.64%). However, in order to elaborate a quality perfume, many other molecules must be taken into account, according to the creative experience of the perfumer, which is subject to confidentiality and chemical analysis according to current legislation, which would avoid fraud, allergy and dermatitis problems.

Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and an efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even many of them have been proved effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarise the available scientific information on these joint-friendly medicinal plants, which have been already tested in human studies: Arnica montana, Boswelliaspp., Curcuma spp., Equisetum arvense, Harpagophytumprocumbens, Salix spp., Sesamumindicum, Symphytumofficinalis, Zingiberofficinalis, Panaxnotoginseng, Whitaniasomnifera.

In this article we investigate the determinants of “New Doctorate Graduates” in Europe. We use data from the EIS-European Innovation Scoreboard of the European Commission for 36 countries in the period 2010-2019 with Pooled OLS, Dynamic Panel, WLS, Panel Data with Fixed Effects and Panel Data with Random Effects. We found that “New Doctorate Graduates” is positively associated, among others, with “Human Resources” and “Government Procurement of Advanced Technology Products” and negatively, associated among others, with “Total Entrepreneurial Activity” and “Innovation Index”. We apply a clusterization with k-Means algorithm either with the Silhouette Coefficient either with the Elbow Method and we found that in both cases the optimal number of clusters is three. Furthermore, we use the Network Analysis with the Distance of Manhattan, and we find the presence of seven network structures. Finally, we propose a confrontation among ten machine learning algorithms to predict the value of “New Doctorate Graduates” either with Original Data-OD either with Augmented Data-AD. Results show that SGD-Stochastic Gradient Descendent is the best predictor for OD while Linear Regression performs better for AD.

Erigeron floribundus (Asteraceae) is an herbaceous plant widely used in the Cameroonian traditional medicine to treat various diseases of microbial and non-microbial origin. In the present study we evaluated the in vitro biological activities displayed by the essential oil obtained from the aerial parts of E. floribundus, namely the antioxidant, antimicrobial and antiproliferative activities. Moreover, we investigated the inhibitory effects of E. floribundus essential oil on nicotinate mononucleotide adenylyltransferase (NadD), a promising new target for developing novel antibiotics, and Trypanosoma brucei, the protozoan parasite responsible for Human African trypanosomiasis. The essential oil composition was dominated by spathulenol (12.2%), caryophyllene oxide (12.4%) and limonene (8.8%). The E. floribundus oil showed a good activity against Staphylococcus aureus (IZD of 14 mm, MIC of 512 µg/mL). Interestingly, it inhibited the NadD enzyme from S. aureus (IC50 of 98 µg/mL), with no effects on mammalian orthologue enzymes. In addition, T. brucei proliferation was inhibited with IC50 values of 33.5 µg/mL with the essential oil and 5.6 µg/mL with the active component limonene. The essential oil exhibited strong cytotoxicity on HCT 116 colon carcinoma cells with an IC50 value of 14.89 µg/mL, and remarkable ferric reducing antioxidant power (TEAC= 411.9 μmol TE/g).

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopment disorder frequently co-occurring with Attention-Deficit/Hyperactivity Disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage ASD core symptoms, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend neuroleptics to reduce psychomotor agitation in people with ASD. However, since children with ASD are often drug-resistant, alternative treatments are often justified. Reports from literature showed that intra-venous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with lower frequency of adverse events compared to convention-al treatments. However, since findings are occasionally inconsistent, IV-VPA is not an approved option in clinical psychiatry. We aim at improving the knowledge on the IV-VPA treatment option in emergency psychiatry in the pediatric age. Methods: We report the case of a 11-year-old boy suffering from a complex neurodevelopmental condition, who experienced a psychotic episode with severe aggressive and disruptive behaviors, successfully treated with IV-VPA. Besides, we conducted an up-dated literature review on this topic. Conclusion: In our case, first-line therapies proved to be ineffective. On the contrary, IV-VPA led to a safe and prompt clinical success, in line with other reports. Based on our literature review, IV-VPA can be highly effective and can reduce the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry.

The mechanism of ciprofloxacin action involves interference with transcription and replication of bacterial DNA, which results in elevated oxidative stress, and bacterial cell death. Vorinostat was shown to induce oxidative DNA damage. In the current work, the possibility for interactive effect of vorinotat on ciprofloxacin-induced cytotoxicity against a number of reference bacteria was investigated. Standard bacterial strains were Escherichia coli ATCC 35218, Staphylococcus aureus ATCC29213, Pseudomonas aeruginosa ATCC 9027, Staphylococcus epidermidis ATCC 12228, Acinetobacter baumannii ATCC 17978, Proteus mirabilis ATCC 12459, Klebsiella pneumoniae ATCC 13883, methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300), and Streptococcus pneumoniae (ATCC 25923). The antibacterial activity of ciprofloxacin with or without pretreatment of bacterial cells by vorinostat was examined using disc diffusion procedure and determination of the minimum inhibitory concentration (MIC) and zones of inhibition of bacterial growth. All tested bacterial strains showed sensitivity to ciprofloxacin. When pretreated with vorinostat, significantly larger zones of inhibition and smaller MIC values were observed in all bacterial strains compared ciprofloxacin alone. As a conclusion, current results showed the possible agonistic properties for vorinostat when it is used together with ciprofloxacin. Future research will be focus on molecular mechanisms possible for such interactive effect.

The structure of arylpiperazine moieties as an important pharmacophore could generate wide pharmacological activities．Arylpiperazine derivatives referred in this paper possessed antitumor activity. The title compounds were crystallized by slow evaporation. 2-(4-(2-(4-Phenylpiperazin-1-yl)ethyl)benzyl)isoindoline-1,3-dione(1), 2-(4-(2-(4-(4-Bromophenyl)piperazin-1-yl)ethyl)benzyl)isoindoline-1,3-dione (2) and 2-(4-(2-(4-(4-Chlorophenyl)piperazin-1-yl)ethyl)benzyl)isoindoline-1,3-dione (3) crystallizes in the triclinic space group P-1 with two molecules in the unit cell. The unit cell parameters for 1 are a = 6.9159(14) Å, b = 9.999(2) Å, c = 16.925(3) Å, α = 88.25(3)°, β = 85.14(3) °, γ = 79.22(3) °. The unit cell parameters for 2 are a = 6.9995(14) Å, b = 9.919(2) Å, c = 17.671(4) Å, α= 97.55(3)°, β = 92.19(3) °, γ = 102.23(3) °. The unit cell parameters for 1 are a = 6.9872(14) Å, b = 9.863(2) Å, c = 17.557(4) Å, α=96.81(3)°, β = 91.89(3) °, γ = 101.74(3) °. Pi-pi interactions were observed between molecules, and compound 2 and 3 showed halogen interactions between molecules nearby, which was different from compound 1.

Cancer, characterized by abnormal cell proliferation driven by genetic mutations, remains a significant health challenge. Tailoring effective therapies depends on factors like tumor location, grade, and stage, alongside patient condition. Leveraging Nano-carrier encapsulated drugs offers a promising avenue, as they accumulate preferentially at tumor sites, enhancing therapeutic efficacy while mitigating side effects. Polymeric Nano-carriers, with their customizable properties, further optimize drug delivery efficiency and specificity. Incorporating active targeting ligands such as antibodies, carbohydrates, peptides, folates, and aptamers-onto polymeric nanoparticle surfaces through techniques like functionalization, adsorption, and conjugation plays a pivotal role in directing therapeutic agents to tumor cells. Consequently, polymeric nanoparticles emerge as the carrier of choice for delivering drugs to various tumor types, including breast, colon, lung, prostate, liver, and spleen tumors.

The novel coronavirus disease (COVID-19) has created immense threats to public health on various levels around the globe. The unpredictable outbreak of this disease and the pandemic situation are causing severe depression, anxiety and other mental as physical health related problems among the human beings. To combat against this disease, vaccination is essential as it will boost the immune system of human beings while being in the contact with the infected people. The vaccination process is thus necessary to confront the outbreak of COVID-19. This deadly disease has put social, economic condition of the entire world into an enormous challenge. The worldwide vaccination progress should be tracked to identify how fast the entire economic as well as social life will be stabilized. The monitor ofthe vaccination progress, a machine learning based Regressor model is approached in this study. This tracking process has been applied on the data starting from 14^th December, 2020 to 24^th April, 2021. A couple of ensemble based machine learning Regressor models such as Random Forest, Extra Trees, Gradient Boosting, AdaBoost and Extreme Gradient Boosting are implemented and their predictive performance are compared. The comparative study reveals that the AdaBoostRegressor outperforms with minimized mean absolute error (MAE) of 9.968 and root mean squared error (RMSE) of 11.133.

The world is suffering from the Coronavirus pandemic and is undergoing some drastic changes in day to day lives. The survey was conducted to analyze the situation of Pharmacy students in India. What are the types of challenges being faced by them during this lockdown due to the Pandemic COVID-19 and how are they getting adapted to the situations? A cross sectional survey was conducted via snowball sampling technique in which 226 participants submitted their response. The chief issue of concern to students was the change in the study pattern which has made the process much difficult for both the faculties and students. Online examination was also be reported as a point of concern. The normal life that we used to have is not acceptable in today’s scenario, hence, the institutions have to make the students more comfortable and adaptable towards the online studies and make the most out of it.

Pharmacists and pharmacies are highly visible and accessible to the public and have long been regarded as a source for immunization services in the United States. As international travel continues to increase and grow in popularity in this country, there is a pressing need for expanded access to preventative health services including routine and travel vaccinations and medications for prophylaxis or self-treatment of conditions that may be acquired overseas. In the United States, the scope of pharmacy practice continues to expand and incorporate these preventable health services to varying degrees on a state-by-state level. As a result, pharmacists can help to increase access to and awareness of the need for these services to insure that patients remain healthy while traveling abroad and that they do not acquire a travel-related disease while on their trip. For those pharmacists interested in starting a travel health service, considerations should be undertaken that ensures that they have the necessary training, education, and skill set in order to provide this specialty level of care and that their practice setting is optimally designed to facilitate this service. Outcomes from studies that have evaluated pharmacy-based travel health services are positive, which further supports the role of the pharmacist in this setting. Therefore, the purpose of this paper is to highlight United States pharmacy laws and regulations, pharmacist training, travel clinic considerations, and patient care outcomes from pharmacy-based travel health services.

Methicillin-resistant Staphylococcus aureus (MRSA) infections, in particular biofilm-organized bacteria, remain a clinical challenge and a serious health problem. Rifabutin (RFB), an antibiotic of the rifamycins class, has shown in previous work excellent anti-staphylococcal activity. Here, we proposed to load RFB in liposomes aiming to promote the accumulation of RFB at infected sites and consequently enhancing the therapeutic potency. Two clinical isolates of MRSA, MRSA-C1 and MRSA-C2, were used to test the developed formulations, as well as the positive control, vancomycin (VCM). RFB in free and liposomal forms displayed high antibacterial activity, with minimal inhibitory concentrations (MIC) ranging from 0.009-0.013 μg/mL and MBIC50 values ranging from 0.008-0.012 μg/mL, in planktonic and biofilm bacteria, respectively. Confocal microscopy studies demonstrated the rapid internalization of unloaded and RFB-loaded liposomes in the bacterial biofilm matrix. In murine models of systemic MRSA-C1 infection, Balb/c mice were treated with RFB formulations and VCM at 20 and 40 mg/kg of body weight, respectively. Obtained data proved the superior therapeutic effectiveness of RFB formulations compared to Control and VCM groups even using a two-fold lower therapeutic dose as demonstrated by significantly reduced bacterial burden and growth index values in major organs. In addition, RFB formulations were the only formulations associated with 100% survival. Globally, this study emphasizes the potential of RFB nanoformulations as an effective and safe approach against MRSA infections.

Suboptimal knowledge of clinical pharmacology, therapeutics, and toxicology (CPT) and poor-quality prescribing are threats to patient safety. Our previous national survey of medical faculty identified limited confidence in medical student graduates’ ability to prescribe safely and an interest in a national prescribing competence assessment. Given the in-person challenges posed by the restrictions related to the COVID-19 pandemic, we aimed to re-evaluate opinions and gauge interest in e-learning resources and assessments. Using public sources, a sampling frame of medical school leaders from all 17 Canadian medical schools, including deans, vice-deans, and program directors for clerkship, residency, and e-learning, were invited to participate in a cross-sectional survey. Survey questions were finalized after several rounds of testing and analyses were descriptive.Of 1448 invitations, 411 (28.4%) individuals reviewed the survey, and among them, 278 (67.6%) completed at least one survey question with representation from all schools. While more than 90% of respondents agreed that medical students should meet a minimum standard of prescribing competence, only 17 (7.9%) could vouch for their school meeting objectives in CPT and many had significant concerns about their own or other schools’ recent graduate prescribing abilities. Given the lack of local CPT eCurricula resources, there was strong interest in a national online course and assessment in CPT. Our national survey results suggest an ongoing inadequacy of medical trainees’ prescribing competence and provide a strong endorsement for both a national online CPT course and assessment during medical school.

Human fungal pathogen Candida albicans causes oral infectious diseases such as oral thrush in immunocompromised patients with hyposalivation, diabetes mellitus, prolonged use of anti-biotics or immunosuppressive medicines and poor oral hygiene. An anti-fungal medication classified as a BCS class II drug, Clotrimazole has high permeability and low solubility in water. It is commercially available as lozenges, which do not uniformly distribute the drug within saliva for local therapy. This results in higher dose frequency and lower patient compliance. Therefore, in this study we proposed a niosomal based subgingival film formulation of clotrimazole for enhancing drug efficacy by improving drug solubilization capacity and improving patient compliance by prolonging the release of drug at the targeted site and reducing the dose frequency to show effective anti-fungal activity. The prepared niosomal film showed good entrapment efficiency and anti-fungal activity. Niosomal film showed better release pattern than drug loaded film.

The increase in the average lifespan and the consequent proportional growth of the elderly segment of society has furthered the interest in studying ageing processes. Ageing may be considered a multifactorial process derived from the interaction between genetic and environmental factors including lifestyle. There is ample evidence in many species that the maximum age attainable (maximum lifespan potential, MLSP) is genetically determined and several mitochondrial DNA polymorphisms are associated with longevity. Many studies have shown that most of the phenotypic characteristics observed in the aging process are the result of the occurrence, with age, of a low grade chronic pro-inflammatory status called "inflammaging", partially under genetic control. The term indicate that aging is accompanied by a low degree of chronic inflammatory, an up-regulation of inflammatory response and that inflammatory changes are common to many age-related diseases. Therefore, the theory of oxidation-inflammation was proposed as the main cause of aging. Accordingly, the chronic oxidative stress, that appears with age, affects all cells and especially those of the regulatory systems, such as the nervous, endocrine, and immune systems and the communication between them. This prevents an adequate homeostasis and, therefore, the preservation of health. It was also proposed that the immune system plays a key role in the aging process, specifically in the rate of aging, since there is a relationship between the redox state and functional capacity of immune cells and longevity of individuals. Moreover, the role of the immune system in senescence could be of universal application. A confirmation of the central role of the immune system in oxi-inflamm-aging is that the administrationintake? of adequate amounts of antioxidants in the diet improves immune function, decreases their oxidative stress, and consequently increases longevity. The promotion of healthy lifestyles is one of the major goals of governments and international agencies all over the world. Human molecular processes are influenced by both physiological pathways and exogenous factors which include, for instance, those originating from diet. Dietary intake has substantive effects on molecular processes of metabolic health. Nutrients can directly regulate physiological changes in human body. In fact, in addition to have an energetic and structural value, nutritional intake provides bioactive molecules which are selectively able to modulate specific metabolic pathways, noticeably affecting cardiovascular and neoplastic diseases development or progress. Numerous bioactive nutrients are being progressively identified and their chemopreventive effects are being described at clinical and molecular mechanism levels. Systematic analyses comprise all “omics” technologies (such as transcriptomics, proteomics and metabolomics) and the goal is to investigate bioactive molecules effects derived from the diet. Nutrigenomic knowledge on physiologic status and disease risk will provide both developments of better diagnostic procedures and of new therapeutic strategies specifically targeted on nutritionally relevant processes. The present review was aimed to understand the molecular mechanisms underlying beneficial effects of bioactive nutrients and nutrigenomics on age-related diseases.

Background and Objectives: Trichomonas tenax is a protozoan, participating in the human oral microflora. It is considered as a potential paradontopathogen. This microorganism is also reported in the respiratory tract. We aimed to analyze the available literature about the prevalence of Trichomonas tenax in the population affected by periodontal disease. Materials and Methods: Тhe searching with keywords: ,,Trichomonas tenax” and “periodontal diseases’’ in Scopus, PubMed and ScienceDirect databases was able to identify several systematic reviews and original articles until July 2023. All studies with suffering from periodontal disease people, mentioned year of publication, country, specified detection methods, total number of tested samples as well as the percentage of those infected with Trichomonas tenax were included. Irrelevant articles were excluded. Results: We found 137 studies, but only 64 studies about distribution of Trichomonas tenax in patients with gum disease underwent qualitative analysis. The highest number of studies have been conducted in Iran, Poland and Iraq. Different methods have been used to detect the unicellular organism, each with different specificity and sensitivity. Conclusions: Interest in Trichomonas tenax has grown considerably since 2000. Because of its association with periodontal disease, Trichomonas tenax role in the inflammatory process shouldn’t be overlooked.

High pressure crystallization technique has been successfully used to prepare an elusive form II of a non-steroidal anti-inflammatory drug, Mefenamic acid. Single crystal of form II was grown at 0.3 GPa from an 4:1 methanol/ ethanol mixture as a solvent using Diamond Anvil Cell. Comparison of crystal structures show that the efficient packing of MA molecules in Form II results from the structural flexibility of MA acid molecules. Compression studies performed on the single crystal of form I resulted in 14 % decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up to this pressure. A reconstructive phase transition is required to induce conformational changes in the structure, which is confirmed by crystallization at high pressure results.

The mechanistic pathway of TEMPO/I₂-mediated oxidative cyclization of N,N-diaryl amino alcohols 1 is investigated in this study. Based on our direct empirical experiments, three key intermediates (the aminium radical cation 3, the α-aminoalkyl radical 4, and the iminium 5), four kind reactive species (radical TEMPO, cationic TEMPO, TEMPO-I and iodo radical) and three kind pathways (1. SET/PCET mechanism, 2. HAT/1,6-H transfer mechanism, 3. Ionic mechanism) were assumed. Under the assumption, nine free energy diagrams are acquired through DFT calculation. From the comparison of the solution phase free energy, some possibility can be excluded and then the chosen plausible mechanisms are concretized with the more stable intermediate 7.

The rise in cannabis use has caused significant concerns pharmacy students’ abilities to counsel patients over cannabis. This study aims to understand pharmacy students’ preparedness to counsel patients with cannabis use disorder (CUD) and evaluate the relationship between knowledge, attitudes towards medical cannabis (MC) and recreational cannabis (RC), and behavior intention (BI) to counsel over CUD. A cross-sectional survey was administered to pharmacy students. Descriptive analysis of sample characteristics were assessed with T-test and one-way ANOVA test. Pearson correlation and linear regression were conducted measuring the strength and direction of relationships. The average scores for knowledge, attitudes towards MC use and RC, and BI were 81% (SD 16%), 4.13 (SD 0.75), 3.28 (0.80), and 2.74 (1.00). Significant correlations were observed between knowledge-attitudes toward MC, knowledge-attitudes towards RC, and attitudes towards RC-BIs. Linear regression indicated attitudes towards MC use and RC, academic year, awareness of MC use legality, obtained knowledge, and past patient interaction were significantly associated with BI on confidence in counseling over CUD. There is a gap in students’ BI to counsel. These findings emphasize the importance of a comprehensive curriculum and state policy and practice changes, enabling future pharmacists to address patient needs related to cannabis use confidently.

We have successfully developed curcumin nanosuspension aimed for oral delivery. The main purpose is to improve bioavailability through enhancing its solubility. The nanoparticles were stabilized using various stabilizers including polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), sodium carboxymethylcellulose (Na-CMC), d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS), and sodium dodecyl sulfate (SDS). The average diameter of particles, microscopic appearance, and sedimentation of each preparation was observed and compared. Each stabilizer demonstrated different degree of inhibition of particle aggregation under electrolyte-containing simulated gastrointestinal (GIT) fluid. Non-ionic stabilizers (PVA, PVP, and TPGS) has shown to preserve the nanosuspension stability against electrolytes. In contrast, strong ionic surfactants such as SDS were found to be very sensitive to electrolytes. The results can provide useful information for the formulators to choose the most suitable stabilizers by considering the nature of stabilizers and physiological characteristics of target site of the drug.

Effective communication is key for healthcare providers to provide optimal care for patients. Pharmacists’ fluency in a patient’s native language is vital to communicate effectively. Additionally, language concordance improves patients’ trust and ensures health equity. In the United States (US), Hispanics are the largest minority group, but only 36% of the pharmacy schools in the US offer Spanish courses in their curriculum. Conversely, Middle Eastern countries have implemented English as the language of instruction in pharmacy schools, though the native language of the patient population is Arabic. The discrepancy between the language of education and the language used by patients might lead to communication problems, thus limiting a pharmacist’s role in practice. This review aims to describe the efforts of pharmacy schools both in the US and Middle Eastern countries to incorporate second language (Spanish and Arabic, respectively) in their curriculum. Spanish language content has scarcely been introduced into the pharmacy curriculum in the US either as didactic elements (elective courses, lab sessions, modules within a course, or co-curricular programs) or as language immersion experiences (rotations and internships nationally or abroad). In Arabic-speaking countries, an Arabic course was introduced to the pharmacy curriculum to enhance students’ communication skills. This review provides an overview of what has been done in various pharmacy programs to prepare students for adequate multilingual speaking. The findings reveal the need for additional strategies to assess the impact of language courses on student performance and patient experience, as well as language competence in pharmacists and pharmacy students.

Ever since pharmacy has become a profession, pharmacist's role has been continuously subjected to changes due to specific influences from historical, socio-economic, political, and scientific context. Nowadays the classic perception of pharmaceutical profession in Community Pharmacy is facing worldwide extinction due to many factors. Modern services, such as online, mail-order, and telephone-order pharmacies are increasingly gaining ground thanks to their ability to facilitate customer demand. However, at the same time, they are endangering “face-to-face” contact, affecting the building of customer loyalty based on direct “human” interaction, and consequently reducing pharmacists to mere commercial figures. Communication is in fact emphasized as the essential element to build a solid and appropriate interpersonal relationship with the client, to make the consultancy process effective, and to strengthen pharmacist's professionalism in community pharmacy. The aim of this work is to analyze pharmacist’s role in modern society by pinpointing the factors affecting pharmacy profession practice. Specific purpose will be improving both the academic training of future professionals and their capacity to approach public relations through a deepened study and practice of behavioral, communication, educational, and sociological methodologies and techniques that would allow the development of more effective communication skills useful for providing an efficient consultancy service.

COVID-19 affected health and wellbeing globally. Graduating nursing students face a variety of stressors and entering the nursing profession during the pandemic added additional stress. Mood, perceived stress, resilience, and coping were assessed in an Australian sample of 112 graduating nursing students, who completed the Brunel Mood Scale (BRUMS), Perceived Stress Scale (PSS-4), and Brief Resilient Coping Scale (BRCS). Mean BRUMS scores for tension, fatigue, and confusion were significantly above population norms, and vigour scores significantly below. Mean PSS-4 scores were reflective of population norms, but showed higher levels of stress for younger and on-campus students compared to those who were older or who studied externally. BRCS data showed that 82.1% of the graduating nursing students were medium or high resilient copers. Mood profiles suggested that 19.6% of participants had elevated mental health risk, 23.2% showed potential risk of burnout, and only 17.9% reported mood profiles associated with positive mental health. High mean tension scores reported by the graduating nursing students indicated apprehension about joining the profession, although stress, resilience and coping scores suggested they were adequately managing the additional stressors generated by a global pandemic.

Abstract: Colistin is a last-resort antimicrobial for treating multidrug-resistant Gram-negative bacteria. Phe-notypic colistin resistance is highly associated with plasmid-mediated mobile colistin resistance (mcr) genes. mcr-bearing Enterobacteriaceae have been detected in many countries, with the emergence of colistin-resistant pathogens a global concern. This study assessed the distribution of mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5 genes with the phenotypic colistin resistance in isolates from diarrheal infants and children in Bangladesh. Bacteria were identified using the API-20E biochemical panel and 16s rDNA gene sequencing. Polymerase chain reac-tions detected mcr gene variants in the isolates. Their susceptibilities to colistin were determined by agar dilu-tion and E-test by minimal inhibitory concentration (MIC) measurements. Over 30.0% (69/225) of isolates showed colistin resistance by agar dilution assessment (MIC> 2.0 μg/mL). Overall, 15.5% of isolates carried mcr genes (7, mcr-1; 17, mcr-2; 13, mcr-3; and co-occurrence occurred in 2 isolates). Clinical breakout MIC val-ues (≥ 4 μg/mL) were associated with 91.3% of mcr-positive isolates. The mcr-positive pathogens include twenty Escherichia spp., five Shigella flexneri, five Citrobacter spp., two Klebsiella pneumoniae, and three Pseudo-monas parafulva. mcr-genes appeared to be significantly associated with phenotypic colistin resistance phe-nomena (p=0.000), with 100% colistin-resistant isolates showing MDR phenomena. Age and sex of patients showed no significant association with detected mcr variants. Overall, mcr-associated colistin-resistant bacte-ria have emerged in Bangladesh, which warrants further research to determine their spread and instigate ac-tivities to reduce resistance.

During the last years there has been a high interest in the development of new purely-organic single-component conductors. Very recently, we have reported a new neutral radical conductor based on the perchlorotriphenylmethyl (PTM) radical moiety linked to a monopyrrolo-tetrathiafulvalene (MPTTF) unit by a -conjugated bridge (1). Interestingly, this system behaves as a semiconductor with high conductivity and small energy gap under high pressure. With the aim of developing a new material with improved conducting properties, we have designed and synthesized the radical dyad 2 which was functionalized with an ethylenedithio (EDT) group in order to improve the intermolecular interactions of the TTF subunits. The physical properties of the new radical dyad 2 were studied in detail in solution to further analyze its electronic structure as well as its potential use as radical conductor in the solid state.

Cannabis sativa is one of the oldest plants utilized by humans for both economic and medical purposes. Although the use of cannabis started millennia ago in the Eastern part of the hemisphere, its use has moved and flourished in the Western Nations in more recent centuries. C. sativa is the source of psychoactive cannabinoids that are consumed as recreational drugs worldwide. The C21 aromatic hydrocarbons are restricted in their natural occurrence to cannabis (with a few exceptions). Delta-9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive component in cannabis with many pharmacological effects and various approved medical applications. However, a wide range of side effects are associated with the use of Δ9-THC, limiting its medical use. In 1966, another psychoactive cannabinoid, Delta-8-tetrahydrocannabinol (Δ8-THC) was isolated from marijuana grown in Maryland but in very low yield. Δ8-THC is gaining increased popularity due to its better stability and easier synthetic manufacturing procedures compared to Δ9-THC. Passing the U.S. Farm Bill in 2018 led to an increase in the sale of Δ8-THC in the United States. The marketed products contain Δ8-THC from synthetic sources. In this review, methods of extraction, purification, and structure elucidation of Δ8-THC will be presented. The issue of whether Δ8-THC is a natural compound or an artifact will be discussed, and the different strategies for its chemical synthesis will be presented. Δ8-THC of synthetic origin is expected to contain some impurities due to residual amounts of starting materials and reagents as well as side products of the reactions. The various methods of analysis and detection of impurities present in the marketed products will be discussed. The pharmacological effects of Δ8-THC, including its interaction with CB1 and CB2 cannabinoid receptors in comparison with Δ9-THC, will be reviewed.

Introduction. Intra-abdominal cystic formations represent heterogeneous pathologies with varied localization and clinical manifestation. The first challenge of a giant intra-abdominal cystic lesion is identifying the organ of origin. The clinical presentation of intra-abdominal cystic lesions varies from acute manifestations to non-specific symptoms or accidental discovery. Case presentation: A 2-year-old girl presents to the emergency unit with a fever of 38.5 Celsius, loss of appetite, and apathy. The investigations showed a gigantic intra-abdominal mass whose organ belonging could not be specified. Postoperatively, a giant mesenteric lymphangioma was evident, which was completely excised. Discussions Giant cystic formations modify the anatomical reports and become space-replacing formations, and the starting point is even more challenging to assess preoperatively. Nevertheless, the careful evaluation of the characteristics of the formation, the effect on the adjacent organs, the age of the patient, and the clinical picture can provide elements of differential diagnosis.

s: The lack of historical employment data for college graduates, the need to solve the system cold-start problem and the consideration of reciprocity of job recommendation in job recommendation, lead to low recommendation satisfaction and immature application of the existing job recommendation methods. The article presents a new approach to job recommendation using college graduates as the object of study. In the screening stage, a semantic keyword iterative algorithm is applied to compute the similarity between the resume and recruitment texts. This algorithm enhances the intersectionality of keywords in the calculation process, maximizing the utilization of resume information to enhance the accuracy of text similarity calculations. The ranking phase utilizes in-school data to build a social network between college graduates and graduated students, and solves the system's cold-start problem by using the social network to recommend jobs for college graduates where graduated students are employed. Building upon the amalgamation of the semantic keyword iterative algorithm and the social network job recommendation method outlined above, we introduce a dual-dimensional matching approach involving specialty and salary. This enhancement is designed to elevate the reciprocity of job recommendations. The analysis of the results indicates that the average satisfaction rate (AR) and normalized discounted cumulative gain (NDCG) values for the newly proposed job recommendation method surpass those of other methods, demonstrating its superior effectiveness. The method caters to the preferences of graduate job seekers, aligns with job recruitment requirements, and offers extensive job search assistance to a broad spectrum of graduates.

The transition from undergraduate dental student to the actual practicing dentist is a crucial phase and ensuring the preparedness of graduates for the complexity and demands of contempo-rary dental practice is a challenging task. This study aimed to evaluate the self-perceived prepar-edness of undergraduate dental students and house officers in the dental colleges of Pakistan. Cross-sectional national study was planned to collect the information from dental students and new graduates in Pakistan. The pre-validated Dental Undergraduates Preparedness Assessment Scale (DU-PAS) was used. Purposive sampling technique was utilized to recruit house officers and undergraduate dental students from 27 dental schools in Pakistan. The data analysis was car-ried out using the R statistical environment for Windows (R Core Team, 2015). The total of 862 responses with 642 females and 219 males were analyzed in the study. Overall, clinical skills score was 30.56+9.08 and score for soft skills was 30.54+10.6. The mean age of the participants was 23.42+1.28. Deficiencies were reported in various soft skills and clinical skills attributes.The results highlighted the strengths and weaknesses of dental students and new graduates in Pakistani den-tal institutions. The findings may be used to further develop and strengthen teaching and training of dental students in Pakistan.