This study aimed to analyze the responsiveness of the 5STS test among stroke patients and to estimate the MCIDs for different severity levels of community ambulation and stages of recovery. The 5STS and comparator instruments [gait speed and Functional Ambulatory Category (FAC)] were evaluated at baseline. These measures were repeated at 4 (Stage 1) and 8 weeks (Stage 2), together with the Global Rating of Change (GROC). The MCIDs were calculated with two anchor-based methods using the GROC as the external criterion. Responsiveness to change for the 5STS was estimated analyzing the correlation with changes in the two comparator instruments and their capacity to discriminate improvement. For the 5STS test, while the MCIDs of the limited community ambulators were similar in the two stages (around 3 s), those of the household ambulators decreased from 1.9 s to 0.72 s. Spearman's rho coefficients showed an acceptable correlation between changes in 5STS and changes for both the FAC and gait speed changes in both stages of recovery. Our study revealed that the 5STS is responsive to functional changes in patients with stroke and that their degree of severity and stage of recovery influence the MCID values of the 5STS.

Introduction: Gastric cancer (GC) is one of the most common cancers in the world. It is a very aggressive and heterogeneous tumor. GC does not cause symptoms, so it is often diagnosed in an advanced stage and associated with poor prognosis. Despite new treatment options, it still remains a therapeutic problem. An important element determining the method of treatment of locally advanced gastric cancer (LAGC) is the assessment of lymph node metastases in preoperative and postoperative imaging and/or histopathological examination.Aim: The assessment of lymphovascular invasion (LVI) in histopathological examination in patients with LAGC after gastrectomy. The groups of patients were divided into patients who received preoperative chemotherapy, patients without preoperative chemotherapy, and all patients. Additionally, we assessed the correlation between the presence of LVI and the number of lymph nodes collected during gastrectomy.Material and method: We collected patients with histologically confirmed GC after gastrectomy. The collected samples were divided into three subgroups: patients with neoadjuvant chemotherapy (NAC), patients without NAC, and all patients. Histopathological examination assessed the presence of LVI infiltration. We then assessed the correlation between the presence of LVI and the presence of lymph node metastasis in GC. Additionally, we assessed the correlation between LVI and the number of lymph nodes evaluated in patients in each group. The statistical analyses were performed using Statistica v13.3 and Microsoft Excel 2021. The significance limit was set at p<0.05.Results:The presence of LVI strongly correlated with node involvement, and the result was statistically significant in all patients and the group of patients treated with NAC. The difference was not statistically significant in the group not treated by NAC. Additionally, we did not observe a correlation between the presence of LVI and the number of metastatic lymph nodes in GC.Summary and Conclusions: The presence of LVI in a patient with GC indicates a high probability of lymph node metastasis, which should translate into therapeutic procedures. Assessment of LVI may help identify potential patients with lymph node metastases, particularly in patients undergoing endoscopic resection without planned lymphadenectomy. It is advisable to expand research on a larger scale in order to establish clear standards in this area.

Since December 2019, the COVID-19 virus has rapidly spread worldwide, prompting the World Health Organization (WHO) to declare it a pandemic and advocate for the widespread use of face masks to mitigate transmission. In this review, we delve into the potential impact of prolonged face mask use on temporomandibular joint (TMJ) health, an area that has garnered limited attention amidst COVID-19 research. Research has revealed that improper mask fit, and constant readjustment can lead to TMJ abnormalities. Similarly, there is a demonstrated correlation between continuous mask usage and increased incidence of headaches, temporomandibular pain, and diminished quality of life. Many studies have highlighted discomfort in the preauricular area, headaches, TMJ noises, headache, jaw pain, and muscle fatigue, as well as dermatological disorders that have been attributed to prolonged mask wear and its impact on TMJ. Our study catalyzes future research endeavors, urging a deeper exploration of the implications of long-term mask wear, not only in the context of the COVID-19 pandemic but also among occupational groups regularly exposed to extended mask use. By unraveling the complexities of TMJ health in the face of evolving preventive measures, we aim to enhance our understanding and safeguard the well-being of mask-wearers worldwide.

Drowsiness is a main factor for various costly defects, even fatal accidents in areas such as construction, transportation, industry and medicine, due to the lack of monitoring vigilance in the mentioned areas. The implementation of a drowsiness detection system can greatly help to reduce the defects and accident rates by alerting individuals when they enter a drowsy state. This research proposes an Electroencephalography (EEG) based approach for detecting drowsiness. EEG signals are passed through a preprocessing chain composed of artifact removal and segmentation to ensure accurate detection followed by different feature extraction methods to extract the different features related to drowsiness. This work explores the use of various machine learning algorithms such as Support Vector Machine (SVM) the K Nearest Neighbor (KNN) the Naive Bayes (NB) the Decision Tree (DT) and the Multilayer Perceptron (MLP) to analyze EEG signals sourced from the DROZY database, carefully labeled into two distinct states of alertness (awake, and drowsy). Segmentation into 10-second intervals ensures precise detection, while a relevant feature selection layer enhances accuracy and generalizability. The proposed approach achieves high accuracy rates of 99.84% and 96.4% for intra (subject by subject) and inter (cross-subject) modes, respectively. SVM emerges as the most effective model for drowsiness detection in the intra mode, while MLP demonstrates superior accuracy in the inter mode. This research offers a promising avenue for implementing proactive drowsiness detection systems to enhance occupational safety across various industries.

Quantum gravity theories rely on a minimal measurable length for their formulations, which clashes with the classical formulation of the uncertainty principle and with Lorentz invariance from general relativity. These incompatibilities led to the development of the generalized uncertainty principle (GUP) from string theories and its various modifications. GUP and covariant formulations of the uncertainty principle are discussed, together with implications for space-time quantization.

Rare Earth Elements (REE), also known as Lanthanides (Ln3+), are a group of 17 elements showing peculiar physical and chemical properties. Unlike technological applications, very little is known about the physiological role and toxicity of Ln3+ on biological systems, in particular on microorganisms (e.g., bacteria), which represent the most abundant domains on our planet. Up to now, very limited studies have been conducted due to Ln3+ precipitation with some anions commonly present in the culture media. Therefore, the development of a minimal medium is essential to allow the study of Ln3+-microbial interactions, limiting considerably the precipitation as insoluble salts. In this regard, a new minimal culture medium capable of solubilizing large amounts of Ln3+, and allowing the growth of different microbial taxa, was successfully developed. Assays have shown that the medium is capable of solubilizing Ln3+ up to 100 times more than other common culture media and allowed the growth of 63 bacteria and 5 fungi. The kinetic growth of one yeast and one gram-positive bacterium has been defined, proving to support superior growth and biomass compared to other commonly used minimal media. Moreover, the sensitivity and uptake/absorption of a Bacillus stratosphericus strain was tested, highlighting its capability to tolerate concentrations up to 10 mM of either Cerium, Gadolinium or Lanthanum and accumulate different quantities of the three.

A strategy to propose solutions to health-related problems recognizes that people, animals, and the environment are interconnected. Fusarium and Neocosmospora are an example of this interaction due to the capable of infecting plants, animals, and human. This review provides information on various aspects of these relations and proposes how to approach fusariosis with a One Health methodology. Here we give a framework to understand infection pathogenesis, through the epidemiological triad and explain how the broad utilization of fungicides in agriculture may play a role in the treatment of human fusariosis. We assess how plumbing systems and hospital environments might play a role as a reservoir for animal and human infections. We explain the role of antifungal resistance mechanism in both humans and agriculture. Our review emphasizes the importance of developing interdisciplinarity research studies where aquatic animals, plants, and human disease interactions can be explored through coordination and collaborative actions.

The study explores how different dimensions of perfectionism influence psychological well-being (PWB) in emerging adults. Literature has deepened the relationships between maladaptive perfectionism (e.g., excessive self-criticism, perceived discrepancy from the standards) and low PWB. Less is known about whether and how adaptive perfectionism (e.g., pursuing personal standards) relates to PWB. Secondly, the study has investigated whether self-compassion (i.e., self-benevolence, seeing personal imperfections as a common condition) may mediate the relationships between adaptive/maladaptive perfectionism and PWB. Participants (N=217, 18-35 y. o.) completed self-report questionnaires measuring: adaptive/maladaptive perfectionism (Almost Perfect Scale-Revised, APS-R: high standards and order/discrepancy, respectively), PWB, and self-compassion (SCS). Adaptive perfectionism resulted associated with PWB, particularly higher presence of purpose in life, environmental mastery, self-acceptance, and personal growth. Conversely, discrepancy resulted the most robust predictor of low PWB (β=-.68), followed by high standards with a positive direction (β=.23; Rc²=.514, p&lt;.001). A strong negative association emerged between discrepancy and SCS (r=-.67, p&lt;.001). A mediation analysis shows that self-compassion has an indirect effect reducing the strength of the relationship between discrepancy and low PWB. Results suggest focusing on self-compassion as a buffer factor that reduces the negative impact of maladaptive perfectionism on psychological well-being. Implications for education and health psychology are discussed.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Despite new methods of diagnostics and treatment as well as extensive biological and immunosuppressive treatment, the etiology of RA is not fully understood. Moreover, the problem of diagnosis and treatment of RA patients is still current and affects a large group of patients. It is suggested that these ER-related features may impair adaptation to chronic stress, inferring the risk of rheumatoid arthritis. The main goal in this study was evaluation of changes in mRNA translation to determine chronic ER stress conditions in rheumatoid arthritis patients. The study group consist of 86 individuals including total 56 rheumatoid arthritis patients and 30 healthy controls. The expression level of mRNA form blood samples of RA patients as well as controls of the PERK-UPR associated genes: p-eIF2, BCL-2, PERK, ATF4, BAX were investigated by Real-Time qPCR. GAPDH expression was used as a standard control. Considering the median, the expression of PERK, BCL-2, p-eIF2, ATF4, BAX was found to be significantly increased in the blood of RA patients compared with the control group. The p-value for the PERK gene was 0.0000000036, the p-value for the BCL-2 gene was 0.000000014, the p-value for the p-eIF2 gene was 0.006948, the p-value for the ATF4 gene was 0.0000056 and the p-value for the BAX gene was 0.00019, respectively. Thus, it can be concluded that targeting of the components of the PERK-dependent UPR signaling pathway via small-molecule PERK inhibitors, may contribute to the development of novel, innovative treatment strategies against rheumatoid arthritis.

Respiratory Syncytial Virus (RSV) continues to pose a significant challenge, contributing to elevated hospitalization rates among children up to 5 years old, with a disproportionate burden on newborn and infants under 6 months old. The unique characteristics of the young immune system make it prone to altered responses to infections and vaccinations, requiring a tailored approach to disease prevention. The recent approval of the maternal RSV vaccine, (brand name ABRYSVO), represents a pivotal advancement in preventive strategies among newborns and infants, marking a milestone in RSV research as the first market-approved maternal vaccine. The present review examines clinical trial data on both recent and previous vaccine candidates, as well as the licensed vaccine, focusing on the prevention of RSV disease in newborns and young infants through the passive acquisition of antibodies following maternal immunization. Additionally, it evaluates the safety profile of these vaccines.

Background/Objectives: Forceps delivery is a crucial obstetrical technique that has been increasingly underutilized in favor of cesarean delivery, despite numerous complications related to cesarean section. The major concerns in assisted vaginal birth (AVB) are the safety and long-term consequences. Thus, we aimed to investigate the neurodevelopmental outcome of children born with forceps delivery up to the age of seven. Methods: A prospective descriptive study was conducted from January 2011 to December 2016 among 49 women from our department in the Clinic for Gynecology and Obstetrics, University Clinical Center of Serbia. The study included women with term singleton cephalic pregnancies. Descriptive statistics were calculated for the baseline demographic and clinical features, whereas the logistic regression analysis was used to explore the association between various perinatal parameters and neurological status of newborns. The Sarnat and Sarnat classification was used to evaluate neurological status of newborns, while long-term neurodevelopmental outcome was assesed with Griffiths Mental Development Scale and additional questions based on the neurologist's clinical practice and experience. Results: Pathological neurological status of the newborn was found in 16.3%, with pathological ultrasound of CNS in 3%. A statistically significant association was observed with Apgar score, odds ratio of 0.575 (95% CI: 0.407–0.813, p = 0.002) and perinatal asphyxia, odds ratio of 9.882 (95% CI: 1.111–87.902, p = 0.04). However, this was unlikely to be related to the mode of delivery. Long-term adverse neurological outcome was seen in three cases, which accounts for 6.4%. These included mild disorders, such as delayed milestone, speech delay and motor clumsiness. Conclusion: The present study highlights the safety of forceps delivery regarding children's neurological outcomes at 7 years of age. This is an important contribution to the modern management of labor, especially in light of increasing rates of cesarean deliveries worldwide.

Objectives: The aim of our current study was to analyze whether the use of important measures of methodological quality and reporting of randomized clinical trials published in the field of cardiovascular disease research have changed over time. Further aim was to investigate whether there was an improvement over time in the ability of these trials to provide a good estimate of the true intervention effect. Methods We conducted two searches in the Cochrane Central Register of Controlled Trials (CENTAL) database to identify cardiovascular clinical research trials published in either 2012 or 2017. Randomized clinical trials (RCTs) trials in cardiovascular disease research with adult participants were eligible to be included. We randomly selected 250 RCTs for both publication year 2012 and 2017. Trial characteristics, data on measures of methodological quality and reporting were extracted and risk of bias for each trial was assessed. Results As compared to 2012 in 2017 there were significant improvements in the reporting of the presence of a data monitoring committee (42.0% in 2017 compared to 34.4% in 2012), and a positive tendency of registering cardiovascular disease research RCTs in clinical trial registries (83.6% in 2017 compared to 72.0% in 2012). On the other hand, we also observed that significantly fewer RCTs reported sample size calculation (60.4% in 2017 compared to 98.4% in 2012) in 2017 as compared to 2012. RCTs in 2017 were more likely to have low overall risk of bias ( RoB ) than in 2012 (29.2% in 2017compared to 21.2% in 2012). Conclusion: As compared to 2012 in 2017 there were significant improvement in some, but not all the important measures of methodological quality. Although more trials in the field of cardiovascular disease research had a lower overall RoB in 2017, the improvement over time was not consistently perceived in all RoB domains.

Objective: to retrospectively evaluate the incidence rate (IR) of echocardiographic signs suspected for pulmonary hypertension (PH) in Systemic sclerosis (SSc) patients after the introduction of a combination therapy with bosentan and sildenafil for treatment or prevention of digital ulcers. Methods: patients attending the Scleroderma Unit of the Universital Hospital of Careggi from July 2010 to July 2023 were enrolled. Patients older than 18 years old, with an history of digital ulcers, treated with bosentan and sildenafil in combination for at least 12 months were included. Patients with a diagnosis of PH preceding the introduction of the therapy were excluded. Demographical data, disease duration, laboratoristic and instrumental data (pulmonary function tests, echocardiographic estimation of pulmonary artery pressure (PAPs) and ultrasonographic value of renal resistive index) were collected. The IR of echocardiographic signs suspected for pulmonary hypertension and their 95% confidence interval were calculated in events/1000 patients-years.Results: forty-seven patients were enrolled; mean disease duration was 12,14 years (SD 5,87). Mean duration of the combination treatment was 78.33 (SD 41.37) months and total at-risk time was 3525 months. Two patients (4,2%) presented echocardiographic signs of PH (sPAP 50 mmHg and 40 mmHg); the IR was calculated to be 6.8/1000 patients-years (95% CI 6,02-7,7). In one of the 2 patients RHC excluded PAH, while the other patient refused to undergo to RHC and PAH could not be confirmed/excluded. A stability of PFTs and echocardiografic PAPs was observed during the observation time. Conclusions: the results of this retrospective study suggest that combination therapy with endothelin receptor antagonist and Phosphodiesterase-5 (PDE5) inhibitors could help in preventing PAH in SSc; prospective case-control studies on larger population are needed to improve knowledge in this field.

Background: Gender differences characterize the prevalence and attitudes toward weight management. Despite limited evidence suggesting greater weight loss in women with anti-obesity pharmacotherapy, gender-specific analysis remains underexplored. This retrospective study aimed to evaluate the gender-specific response to liraglutide 3.0 mg treatment in people with obesity without type 2 diabetes (T2D). Methods: Data were collected from 47 patients (31 women, 16 men), with age > 18 years, BMI ≥ 30 kg/m^2, absence of T2D, and with exclusion of prior anti-obesity treatment, comorbidities, or bariatric surgery. Only patients who maintained the liraglutide 3.0 mg dose for at least 6 months were included. Results: Both sexes showed significant reductions in weight and BMI at 3 and 6 months. Men achieved greater weight loss (WL), BMI reduction, % WL, WL >5% and >10% than women, and they also showed more significant improvements in metabolic parameters (total and LDL cholesterol, Fibrosis-4 Index FIB-4). No significant gender differences were observed in glucose metabolism or renal function. Conclusion: This study showed a greater therapeutic effect of liraglutide 3.0 mg in men. Given men's higher risk of cardiovascular disease (CVD), and underrepresentation in clinical weight loss programs, these findings may increase male engagement and improve their CVD risk.

Due to the significant price difference, expensive oils like olive oil are often blended with cheaper edible oils. This practice of adulteration in edible oils, aimed at increasing profits for producers, poses a major concern for consumers. Furthermore, adulteration in edible oils can lead to various health issues impacting consumer well-being. In order to meet the requirements of fast, non-destructive, universal, accurate and reliable quality testing for edible oil, the oblique-incidence reflectivity difference (OIRD) method combined with machine learning algorithms was introduced to detect a variety of edible oils. The prediction accuracy of Gradient Boosting, K-Nearest Neighbor, and Random Forest models exceeded 95%. Experimental results indicate that the OIRD method can serve as a powerful tool for detecting edible oils.

The ongoing SARS-CoV-2 pandemic has raised concerns surrounding immunological protection against the virus, particularly for people with inborn errors of immunity (IEI). While COVID-19 vaccination induces robust antibody, memory B-cell, and T-cell responses in healthy individuals, how well vaccination protects people with IEI against infection and severe disease remains unclear – especially in the context of new viral variants and vaccine formulations – leading to anxiety, ongoing self-isolation, and repeated vaccination with limited evidence of increased efficacy. Whilst most people with IEI generate some level of cellular and/or humoral immunity to COVID-19 vaccination, the level of protection and durability of the response are unclear. Alongside vaccination, antibody-based therapeutics are aimed at limiting infection and severe disease in this cohort. Immunoglobulin replacement therapy (IgRT) provides passive immunity in antibody-deficient individuals. However, to successfully prevent SARS-CoV-2 infection, a sufficient number of neutralizing antibodies must be present in product. While antibodies against circulating variants are eventually present in IgRT products (both from natural infection and vaccination of the donors), evidence of their capacity to recognize new variants is limited. Furthermore, while antibody-based pre- and post-exposure prophylaxis can be effective, they are susceptible to decreased efficacy in the context of variant evolution. This review provides an in-depth overview of current knowledge about COVID-19 vaccine efficacy in IEIs, the efficacy of SARS-CoV-2-specific antibody products, and knowledge and technological advances required for continued protection of people with IEI.

Introduction: Treating elbow fracture-dislocation is a challenge, especially in the situation of basal-coronoid trans-ulnar fracture. The study ams to explain whether or not the minimal invasive surgery (MIS) would be feasible in elbow dislocation with coronoid fracture. Materials & Methods: At Taipei Veterans General Hospital, patients who had elbow dislocations with coronoid process fractures underwent single one surgeon’s MIS techniques which included the fluoroscopy-guided ulnar anteromedial (FGUAM) approach in the stage of reducing coronoid process. When there is a proximal ulnar fracture, the posterior incision should be necessary, followed by the incision over the lateral or medial elbow in treating radial fractures or ligament injuries. Results: The Flow Diagram about approach recommendation was established in base of defining MIS as not to do cross-plane dissection. Anteriorly rigid fixation for the coronoid process was also emphasized. Conclusions: MIS can be achieved by multiple limited surgical incisions. However, if there is an unstable ulnar metaphysis or ligament avulsion fracture, the posterior approach has to be extended and the so-called MIS fails to be established.

Daridorexant, as the first Dual Orexin Receptor Antagonist (DORA) marketed in Europe, offers a novel therapeutic approach to insomnia. However, data regarding its real-world safety are scarce. Thus, the aim of this study was to assess its safety profile using a large-scale pharma-covigilance database. Daridorexant-related Adverse Drug Reaction (ADR) reports from the FDA Adverse Event Reporting System were scrutinized, and ADRs were selected using reporting odds ratio (ROR) as a measure of disproportionality. Frequencies of events related to daridorexant were compared to all other drugs (reference group, RG1) and only to other DORAs (RG2). Only significant disproportionalities to both RGs were evaluated in-depth. A total of 845 dari-dorexant-related reports were selected; nightmares (n = 146; Dari vs. RG1: ROR = 113.74; 95%CI[95.13, 136]; Dari vs. RG2: ROR = 2.35; 95CI%[1.93, 2.85]), depression (n = 22; Dari vs. RG1: 2.13; [1.39, 3.25]; Dari vs. RG2: ROR = 2.31; 95CI%[1.45, 3.67]), and hangover (n = 20; Dari vs. RG1: ROR = 127.92; 95CI%[81.98, 199.62]; Dari vs. RG2: 3.38; [2.04, 5.61]) were considered as safety signals. These data provide valuable insights into the real-world safety profile of dari-dorexant, supporting the existence of safety signals related to nightmares, depression, and hang-over.

The rapid increase in metabolic diseases occurred in the last three decades in both industrialized and developing countries has been related to the rise in sugar-added foods and sweetened beverages consumption. An emerging topic in the pathogenesis of metabolic diseases related to modern nutrition is the role of Advanced Glycation Endproducts (AGEs). AGEs can be ingested with high temperature processed foods, but also endogenously formed as consequence of a high dietary sugars intake. Animal models of high sugars consumption, in particular fructose, have reported AGEs accumulation in different tissues in association with peripheral insulin resistance and lipid metabolism alterations. The in vitro observation that fructose is one of the most rapid and effective glycating agent when compared to other sugars has prompted the investigation of the in vivo fructose-induced glycation. In particular, the widespread employment of fructose as sweetener has been ascribed by many experimental and observational studies for the enhancement of lipogenesis and intracellular lipid deposition. Indeed, diet-derived AGEs have been demonstrated to interfere with many cell functions such as lipid synthesis, inflammation, antioxidant defences, and mitochondrial metabolism. Moreover, emerging evidences also in humans suggest that this impact of dietary AGEs on different signalling pathways can contribute to the onset of organ damage in liver, skeletal and cardiac muscle, and brain, affecting not only metabolic control, but global health. Indeed, the here reviewed most recent reports on the effects of high sugars consumption and diet-derived AGEs on human health suggest the need to limit the dietary sources of AGEs, including added sugars, to prevent the development of metabolic diseases and related comorbidities.

Minimal rotating thermodynamic systems are addressed. Particle m placed into the rotating symmetrical double-well potential (bowl), providing binary logical system is considered. The condition providing the transfer of the particle from one frictionless half-well to another, and in this way possibility to record 1 bit of information is derived. The procedure of recording turns out to be irreversible; it is impossible to return the particle to its initial state under rotation about the same axis. The same rotating double-well system exerted to the thermal noise is considered. Minimal rotating thermal engine built of the rotating chamber, movable partition and the particle confined within the chamber is treated. Rotation of the system displaces the partition; thus, enabling erasing of one bit information. Erasing of 1 bit of information is due to the inertia (centrifugal force) acting on the partition. Isothermal expansion of the “minimal gas” expectedly gives rise to the Landauer bound. Compression of the “gas” with the rotation around the same axis is impossible and demands the additional axis of rotation. The interrelation between the possibility of recording/erasing information and the symmetry of the system is considered.

Background: Bacteria can survive antibiotic exposure by mechanisms like tolerance without a shift in antimicrobial susceptibility. In this study, we investigated the presence of tolerance to three antimicrobials, ceftriaxone (CRO), azithromycin (AZM), and ciprofloxacin (CIP), in clinical isolates and WHO reference panel of N. gonorrhoeae and explored the prevalence between urogenital and anorectal infection sites. Methods: We examined 66 N. gonorrhoeae clinical isolates, evenly divided between anorectal and urogenital infection sites, using a modified tolerance disk (TD test) for three antibiotics. The isolates underwent a three-step incubation process wherein the isolates were exposed to an antibiotic disc for 20 hours of incubation (Step I), followed by the replacement of the antibiotic disc with a nutrient disc for overnight incubation (Step II) and additional overnight incubation with extra nutrients (Step III). Results: Four isolates were lost due to contamination. Of 62 clinical isolates, 7 exhibited tolerance to AZM, with 6 from anorectal and 1 from urogenital sites (p = 0.0496). Tolerance to CRO was observed in 11 isolates, which was significantly associated with the infection site, with 9 from the anorectum, and 2 from the urogenital site being tolerant (p = 0.02). Tolerance to CIP was found in 11 isolates, but was not significantly associated with the infection site. Tolerance was also detected in 8 (K, M, N, O, P, U, V, W) out of the 14 WHO (World Health Organization) reference strains, with varying patterns of tolerance to CRO (n=8), CIP (n=2) and AZM (n=1). Conclusion: This study identified CRO, AZM, and CIP tolerance in clinical Neisseria gonorrhoeae isolates. Significant variations in tolerance proportions between anorectal and urogenital infection sites, particularly for CRO, were observed. Additionally, tolerance was detected in WHO reference strains.

Non-coding RNAs have been described as crucial regulators of gene expression and guards for cellular homeostasis. Some recent papers are focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which made them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complex. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that reminds a vault. Their sequence and structure are highly evolutionary conserved and show many similarities in comparison with different species, but vault RNAs show various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of the human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy.

C. auris is a newly emerging yeast, raising public health concerns due to its outbreak potential, lack of protocols for decontamination and isolation of patients or contacts, increased resistance to common antifungals and associated high mortality. This research aimed to describe the challenges related to identifying the outbreak, limiting further contamination, and treating affected individuals. We retrospectively analysed all cases of C. auris detected between October 2022 and August 2023, but our investigation focused on a three-month-long outbreak in the department of cardio-vascular surgery and the related intensive care unit. Along with isolated cases in different wards, we identified 13 patients who became infected or colonized in the same area and time, even though the epidemiological link could be traced only in 10 patients, according to the epidemiological investigation. In conclusion, our study emphasizes the substantial challenge encountered in clinical practice when attempting to diagnose and limit the spread of an outbreak. Therefore, it is crucial to promptly apply contact precaution measures and appropriate environmental cleaning, from the first case detected positive.

The physical roots, interpretation, controversies and precise meaning of the Landauer Principle are surveyed. Landauer's principle is a physical principle pertaining to the lower theoretical limit of energy consumption of computation. It states that an irreversible change in information stored in a computer, such as merging two computational paths, dissipates a minimum amount of heat kBTln2 per a bit of information to its surrounding. The Landauer Principle is discussed in the context of fundamental physical limiting principles, such as the Abbe diffraction limit, the Margolus-Levitin limit and the Bekenstein limit. Synthesis of the Landauer bound with the Abbe, Margolus-Levitin limit and Bekenstein limits yields the minimal time of computation, which scales as τmin~hkBT. Decrease in a temperature of a thermal bath will decrease the energy consumption of a single computation, but, in parallel, it will slow the computation. The Landauer principle bridges between John Archibald Wheeler “it from bit” paradigm and thermodynamics. Experimental verifications of the Landauer Principle are surveyed. Interrelation between thermodynamic and logical irreversibility is addressed. Generalization of the Landauer principle to the quantum and non-equilibrium systems is addressed. Landauer Principle represents the powerful heuristic principle bridging the physics, information theory and computer engineering.

The impact of systemic vascular resistance (SVR) in hypertrophic (HCM) and amyloid cardio-myopathies has been seldom investigated. We studied pressure-strain loop derived myocardial work (MW) indices and SVR in patients with either sarcomere HCM or wild type transthyretin cardiac amyloidosis (ATTR), presented with heart failure and preserved left ventricular ejection fraction (HFpEF) at the outpatient cardiology units at Messina and Catania University Hospitals (Italy). Patients were in sinus rhythm and needed to have good transthoracic ultrasound imaging quality to undergo transthoracic strain-echocardiography. Other than conventional parameters, SVR and GWI (global work index) were measured. Based on cross-tabulation (a way to assess the ventricular-arterial coupling), the patients were then classified in 4 classes according to the cut-off values suggested by previous studies of 1,440 dyne/s/cm-5 for SVR (Stefadouros et al., 1973) and 1576 mm Hg% for GWI (Olsen et al., 2022). Sixty patients, 30 in each group, aged 61±16 years, 78% males, were studied. HCM were younger than ATTR patients and in a better clinical status (23% HCM vs 77% ATTR were NYHA class 3, p<0.001). Overall, 51 patients (85%) showed high SVR, of whom 21 were HCM (70%) and 30 ATTR (100%) (p<0.005). Both, SVR and GWI were impaired (the poorest class C) in 43% HCM patients (with greater left ventricular concentric hypertrophy) vs 93% of ATTR patients (in advanced NYHA class) (p<0.001). In conclusion, assessing SVR and GWI in HFpEF patients with HCM or ATTR can help clinicians to interpret the pathophysiological and clinical features of such complex diseases.

Background: The resurgence of syphilis, primarily in MSM populations, has necessitated novel prophylactic strategies, such as the use of doxycycline post-exposure prophylaxis (doxy-PEP). However, the potential for increased doxycycline use to select for tetracycline resistance represents significant challenges in managing this sexually transmitted infection. This study aims to identify chromosomal mutations associated with tetracycline resistance in Spirochaetales to inform treatment strategies and surveillance measures.Methods: Whole genome sequences (WGS) from the Spirochaetales order, including 4,355 genomes, were analyzed for the presence of mutations in 16S rRNA and non-synonymous mutations in the rpsC and rpsJ genes. The study utilized WGS from GenBank® and sequence data from the PubMLST Treponema pallidum isolate collection. Genetic resistance to tetracycline was detected using a combination of BLASTN searches and gene-gene analysis. Results: A transition mutation TGA to TGG at positions 965-967 in the 16S rRNA gene was detected in 5.6% of Treponema spp. and 3.97% of Spirochaeta spp. genomes. The rpsJ gene exhibited a V57G amino acid substitution across a significant subset of Treponema spp. Notably, the V57K mutation was common in Spirochaeta spp. The rpsC gene had the H178Q mutation and was found to be present in the Spirochaetales bacterium.Conclusion: The identification of mutations associated with tetracycline resistance in Spirochaetales provides a foundation for the development of rapid molecular diagnostics and guides the clinical selection of antibiotics for syphilis treatment. This study underscores the complexity of antibiotic resistance mechanisms and the critical importance of surveillance in the era of antibiotic prophylaxis for STI management.

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer characterized by two etiologies: the first one, observed in most cases, is attributed to Merkel cell polyomavirus (MCPyV), a DNA tumor virus, while the second one is due to ultraviolet (UV) radiation exposure. Currently, there are limited diagnostic, prognostic, and therapeutic biomarkers available for MCC. MicroRNAs (miRNAs) are small RNA molecules that do not code for proteins but regulate various cellular processes, including cell cycle progression, proliferation, differentiation, and apoptosis. The dysregulation of miRNAs has been associated with a wide range of cancers since they can act as either tumor suppressors or oncogenes. This paper aims to collect, summarize and re-organize the recent discoveries concerning miRNAs, whose dysregulation in the pathogenesis and progression of MCC is slowly emerging. Furthermore, the potential clinical applications of miRNAs as diagnostic biomarkers, possible differentiation between MCPyV-related and unrelated MCC, predictors of response to therapy and prognostics are also discussed. From this review, it emerges that miRNAs may have, in the near future, the potential to become clinically significant in improving the diagnostic accuracy, prognostic evaluation, and therapeutic options of MCCs. Finally, the new perspectives on the poorly explored field of artificial intelligence in MCC are provided.

Severe inherited alpha-1 antitrypsin deficiency (AATD) is an autosomal genetic condition linked to chronic obstructive pulmonary disease (COPD). The significance of heterozygous, milder deficiency variants (Pi*M, Pi*S, Pi*Z) is less clear. We studied AATD genotypes in 145 children (up to 72 months old) with assessed wheezing severity using the Pediatric Respiratory Assessment Measure (BCCH PRAM score). A control group of 74 children without airway obstruction was included. AAT concentration and Pi phenotype were determined from dry blood spot samples using nephelometry and real-time PCR; PiS and PiZ alleles were identified by isoelectrofocusing. Among the wheezers, the Pi*S allele incidence was 2.07% (3 cases) and Pi*Z allele was 6.9% (10 cases). The Pi*Z allele frequency was higher in wheezers compared to controls (44.8% vs. 20.27%) and the general Lithuanian population (44.8% vs. 13.6%) and was similar to adult COPD patients in Lithuania: Pi*S 10.3% vs. 15.8% and Pi*Z 44.8% vs. 46.1%. No association was found between AAT genotypes and wheezing severity. Finding that wheezer children exhibit a frequency of Z* and S* alleles like that found in adults with COPD suggests a potential genetic predisposition that links early wheezing in children to the development of COPD in adulthood. Larger cohort studies are needed to confirm this finding.

Neurological involvement following COronaVIrus Disease 19 (COVID-19) is thought to have a neuroinflammatory etiology. Co-ultraPEALut (an antiinflammatory molecule) and luteolin (an antioxidant) yielded promising results as neuroinflammation antagonists. This study aimed at describing cognitive impairment in post-COVID patient treated with co-ultraPEALut. Montreal Cognitive Assessment (MoCA), Prospective-Retrospective Memory Questionnaire (PRMQ), Fatigue Severity Scale (FSS) and a subjective evaluation were administered at baseline and after 10 months. Co-ultraPEALut-treated patients were retrospectively compared with controls. 26 co-ultraPEALut-treated patients showed significant improvement in PRMQ (T0: 51.94±10.55, T1: 39.67±13.02, p

Background and Objectives: ARNE score was developed for the prediction of difficult airway for both general and ENT surgery with a universal cut-off value. We tested the accuracy of this score in the case of laryngeal surgery and provided an insight of its combination with flexible laryngoscopy. Materials and Methods: This prospective pilot clinical study included 100 patients who were being scheduled for microscopic laryngeal surgery. We have calculated ARNE score for every patient and flexible laryngoscopy was provided preoperative. Difficult intubation was assessed according to intubation difficulty score (IDS). Results: A total of 33% patients had difficult intubation according to IDS. ARNE score showed to be accurate for prediction of difficult intubation in laryngology with P&lt;0.0001 and AUC 0.784. Flexible laryngoscopy showed to be an independent parameter with P&lt;0.0001 and AUC 0.766. We have defined a new cut-off value of 15.50 for laryngology, according to AUC curve. After the patients were divided in two groups, according to the new cut-off value and provided cut-off value, AUC improved to 0.707 from 0.619 respectively. Flexible laryngoscopy improved the prediction model of ARNE score to AUC 0.882 and of new cut-off value to AUC 0.833. Conclusions: It is recommended to use flexible laryngoscopy together with ARNE score in difficult airway prediction in patients with laryngeal pathology. Also, universally recommended cut-off value of 11 can not be effectively used in laryngology and a new cut-off value of 15.50 is recommended.

Newborn screening (NBS) is hailed as a public health success, but little is known about long-term outcomes following a positive newborn screen. There has been difficulty gathering long-term follow-up (LTFU) data consistently, reliably, and with minimal effort. Six programs developed and tested a core set of minimal LTFU data elements. After an iterative data collection process and the development of a data collection tool, the group agreed on minimal LTFU data elements. The denominator captured all infants with an NBS diagnosis, accounting for children who moved or died prior to the follow-up year. They also agreed on three LTFU outcomes: if the child was still alive, had contact with a specialist, and received appropriate care specific to their diagnosis within the year. The six programs representing NBS public health programs, clinical providers, and research programs provided data across multiple NBS disorders. In 2022, 83.8% (563/672) of the children identified by the LTFU programs were alive and living in the jurisdiction; of those, 92.0% (518/563) saw a specialist, and 87.7% (494/563) received appropriate care. The core LTFU data elements can be applied as a foundation to address the impact of early diagnosis by NBS within and across jurisdictions.

Minimally invasive approaches to the aortic valve have been described since 1993, with great hopes that they would become universal and facilitate day-case cardiac surgery. The literature has shown that these procedures can be undertaken with equivalent mortality, similar operative time, comparative cost and some benefits in hospital length of stay. The competing efforts of the transcatheter aortic valve implantation for these same outcomes have provided an excellent range of treatment options for patients from the Heart Team. We describe the current state of the art, including technical considerations, caveats and complications of minimal access aortic surgery and predict future directions in this space.

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.

Candida spondylodiscitis (CS) is a rare disease, for which therapeutic option are limited to fluconazole or echinocandins and the treatment should be administered up to 12 months. In case of reduced azole susceptibility, there is a scarcity of therapeutic options with adequate bone penetration and limited toxicity. We report the first case of successful use of rezafungin for a spondylodiscitis due to Candida parapsilosis with reduced susceptibility to azoles. The patient, affected by paraplegia and short bowel syndrome, was diagnosed with CS with culture on vertebral biopsy guided by a 18-FDG-PET/CT scan. He received rezafungin 200 mg weekly for 26 weeks, after 10 weeks of previous antifungal treatment. He had a full clinical, radiologic and biochemical response to the therapy with rezafungin, with no adverse effects. Rezafungin is a promising therapy for Candida osteomyelitis, especially when first line therapies are ineffective or contraindicated.

There is little doubt that the efficacy of MnDPDP and its therapeutic improved counterpart Ca4Mn(DPDP)5 mainly depends on their MnSOD-mimetic activity when it comes to their potential use as rescue medicines, during e.g., acute myocardial infarction. However, pharmacokinetic considerations suggest that the efficacy of MnDPDP on Pt2+-associated neurotoxicity depends on another action of this drug. Electron Paramagnetic Resonance (EPR) studies have demonstrated that Pt2+ outcompetes Mn2+ and endogenous Zn2+ from binding to fodipir (DPDP), and hence suggest that the previously reported CIPN protective efficacy of MnDPDP is a result of chelation and elimination of Pt2+ by DPDP, which in turn suggests that Mn2+ is unnecessary for efficacy when it comes to oxaliplatin-associated CIPN.

This study proposes an innovative pharmacovigilance approach, VIGI-4, leveraging ChatGPT Teams Pro version. Our method involves aggregating data from all phase 4 studies published in February 2024 to identify adverse reactions. These results are categorized by disease state alphabetically, demonstrating the method's capacity to generate structured and easily navigable outputs. The results section is tailored to exemplify the valuable, actionable insights attainable through our workflow. This research emphasizes the game-changing potential of integrating advanced technologies such as ChatGPT into pharmacovigilance, signaling a new era in safeguarding drug safety.

Background: Cardiovascular (CV) morbidity and mortality are many times higher in chronic kidney disease (CKD), as well as IgA nephropathy (IgAN), than in the general population. The occurrence of metabolic syndrome (MetS) and metabolic risk factors are independent risk factors for CV disease and renal progression. The study aimed to determine the prognostic role of metabolic profiles in a homogenous group of CKD patients. Methods: One hundred and forty-five IgA nephropathy patients (92 male, 53 female, age 54.7 ± 13 years) with CKD stage 1-4 were investigated and followed for a median of 190 months. The composite (CV and renal) endpoints included all-cause mortality and any CV event such as stroke, myocardial infarction, revascularization (CV), end-stage renal disease, and renal replacement therapy (renal). Results: Patients with MetS had significantly more endpoint events (16/27 patients vs. 15/98 patients, p = 0.001) compared to the nonMetS group. Of the secondary endpoints (CV or renal separately), the rate of the renal and CV endpoints was significantly higher in the MetS group (p = 0.001 and p = 0.029). The primary endpoint independent predictors of survival were dyslipidemia, eGFR, hemoglobin, urine albuminuria, and diabetes mellitus, as determined by Cox regression analysis. Independent predictors of secondary renal endpoint were dyslipidemia, hemoglobin, urine albumin, and eGFR. Predictors of secondary cardiovascular endpoints were gender, BMI, and diabetes. Kaplan-Meier curves showed significant differences in MetS and non-MetS when examined at the combined endpoints (CV and renal) or at each endpoint separately. The primary endpoint rate increased significantly with the increased number of MetS components (MetS comp. 0 vs. MetS comp. 2+, primary endpoints, p = 0.012). Conclusion: Our results showed that the metabolic profile has a prognostic role not only for renal endpoints but also for CV endpoints in IgAN. BMI, hyperuricemia, hypertension, and diabetes have a predictive value for the prognosis of IgA nephropathy.

The study aimed to determine the effect of heat stress (HS) on reproductive parameters [calving to first service (CTFS) and first service conception rate (FSCR)] and general physiological responses [rectal temperature (RT) and respiratory rate (RR)] in tropical Holstein Friesian dairy cows raised in Ratchaburi province, Thailand. Cows were divided into a moderate HS (n = 22) and a mild HS (n = 22) group. Cycling cows were detected and injected with PGF2α at the beginning of the experimental period. Reproductive and physiological parameters were recorded. The average temperature humidity indices experienced by the cows were 80.67 ± 0.79 and 77.81 ± 1.09 for the moderate and mild HS groups, respectively. Cows showed significantly lower RT and RR in the mild (38.47 ± 0.21°C and 41.04 ± 4.55 bpm, respectively) than in the moderate HS group (38.87 ± 0.15°C and 51.17 ± 10.52 bpm). Under mild HS, cows showed a better response to injection of PGF2α than those under moderate HS. The percentage of cows that ovulated after being induced by PGF2α and showed estrus signs was higher in the mild than the moderate HS groups (54.55% versus 18.18%). Furthermore, the FSCR of cows under mild HS tended to be higher than in the moderate HS group (54.55 % and 42.11%, respectively), while the average CTFS interval was significantly shorter under mild than moderate HS (69.47 ± 18.18 and 84.60 ± 27.68, respectively). These results indicate that HS impairs reproductive performance in cross-bred Holstein cows, especially in moderate HS conditions.

How hematopoietic stem and progenitor cell (HSPC) fate decisions are affected by genetic alterations acquired during AML leukemogenesis is poorly understood and mainly explored in animal models. Here, we studied isocitrate dehydrogenases (IDH) genes mutations in the human model of HSPC and provide a review of the literature on this topic. IDH1/2 mutations occur in ~20% of AML, are recognized among the mutations earliest acquired during leukemogenesis, and are target of specific inhibitors (ivosidenib and enasidenib, respectively). In order to investigate the direct effects of these mutations on the HSPC we expressed by lentiviral transduction either IDH1-R132H or IDH2-R140Q mutants into human CD34+ healthy donor cells and analyzed the colony-forming unit (CFU) ability. CFU ability was dramatically compromised with a complete trilineage block of differentiation. Strikingly, the block was reversed by the specific inhibitors, confirming it was a specific effect induced by the mutants. In line with this observation, the CD34+ leukemic precursors isolated from a patient with IDH2-mutated AML at baseline and during enasidenib treatment showed over time a progressive and marked improvement of their fitness in terms of CFU ability and propensity to differentiate, attaining clonal trilinear reconstitution of hematopoiesis and complete hematological remission.

Minimal access cardiac surgery appears to be the future. It is increasingly desired by cardiologists and demanded by patients who perceive superiority. Minimal access coronary artery revascularisation has been increasingly adopted throughout the world. Here we review the history of minimal access coronary revascularization and see that it is almost as old as the history of cardiac surgery. Modern minimal access coronary revascularization takes a variety of forms – namely minimal access direct coronary artery bypass grafting (MIDCAB), hybrid coronary revascularisation (HCR) and totally Endoscopic Coronary Artery Bypass Grafting (TECAB). It is noteworthy that there is significant variation in nomenclature and approaches for minimal access coronary surgery and this truly presents a challenge to comparing the different methods. However, these approaches are increasing in frequency and proponents demonstrate clear advantages for their patients. The challenge that remains, as for all areas of surgery, is demonstrating superiority of these techniques over tried and tested open techniques which is very difficult. There is a paucity of randomized controlled trials to help answer this question, and the future of minimal access coronary revascularisation to some extent is dependent on such trials. Thankfully some are underway and the results eagerly anticipated.

Innovation is a crucial issue in healthcare services since it can affect job-related variables such as productivity, satisfaction and burnout. The aim of our study was to examine the impact of innovation support on quiet quitting, innovative behavior and innovation outputs among nurses. We conducted a cross-sectional study in Greece during April 2024. We employed a convenience sample of nurses. We used the following instruments: (a) the Innovation Support Inventory (ISI) to measure innovation support, (b) the Quiet Quitting Scale (QQS) to measure quiet quitting, (c) the Innovative Behavior Inventory (IBI) to measure innovative behavior, and (d) the Innovation Outputs (IO) scale to measure innovation outputs. Our multivariable analysis identified a negative relationship between innovation support and quiet quitting. Moreover, we found that managerial support and cultural support improved several aspects of innovative behavior, such as idea generation, idea search, idea communication, implementation starting activities, involving others, and overcoming obstacles. Additionally, managerial support improved innovation outputs. Our findings suggested the positive impact of innovation support on quiet quitting, innovative behavior and innovation outputs among nurses. Organizations and nurses’ managers should establish an innovative working environment to improve nurses’ passion, motives and productivity.

D-dimer testing in combination with clinical assessment is commonly used to diagnose suspected DVT and pulmonary embolism. However, as D-dimer levels are physiologically higher in elderly patients, this test loses clinical specificity in the setting of geriatric patients. The aim of our study was to investigate the changes in D-dimer levels with age and the specificity of the D-dimer test in the diagnosis of pulmonary embolism. 1617 elderly patients consecutively admitted to the Geriatric Emergency Care Department of the INRCA-IRCCS hospital between January 2013 and February 2014 and for whom D-dimer results were available were included. The D-dimer immunoturbidimetric assay was performed on a cs-2100i Sysmex Siemens using a conventional cut-off level of 500 µg/L. The median D-dimer level was 1200 [550-2990] µg/L FEU, and the percentage of patients with D-dimer levels below the conventional cut-off was only 22.1%. As expected, there was a significant age-related increase in D-dimer, even when sex was considered, and a significant decrease in the specificity of D-dimer assay with age. The most established use of D-dimer testing is in the diagnosis of deep vein thrombosis or pulmonary embolism. Our study confirms the need for an age-adjusted cut-off for D-dimer testing in geriatric patients.

Background: Both hypertension and carotid atherosclerosis are independent risk factors for cardiovascular disease. Understanding their combined impact could enhance risk assessment and management strategies. Hypothesis: We hypothesized that the synergistic effects of hypertension and carotid plaques would increase the risk of both cardiovascular events and all-cause mortality. Methods: A follow-up study was conducted at the Preventive Cardiology department of Vilnius University Hospital Santaros klinikos between 2012 and 2021. The study recruited participants aged 40-60 who did not have overt CVD and were part of the Lithuanian High Cardiovascular Risk primary preventive program. The study collected demographic and clinical data, including an ultrasound assessment of carotid plaque. The participants were monitored for 4-10 years for CVD events and all-cause mortality. Results: Among 6,138 participants, 954 (16%) experienced cardiovascular disease (CVD) events. The presence of carotid plaque on both sides was significantly associated with CVD events, myocardial infarction, and all-cause mortality. However, the combination of hypertension and carotid plaque did not significantly increase the risk for CVD events, stroke, or all-cause mortality. Conclusion: The combination of hypertension and carotid plaque did not significantly increase the risk of CVD events or all-cause mortality. CV events depend on the spread of the atherosclerosis process in the carotid vessels.

Visual exploration of complex data helps interpretation, especially in the case of omics data analysis in life sciences and clinical research. Generating and analysing omics data requires bioinformatic skills, while they are interpreted by domain experts, for whom parsing large and complex data structures may be challenging. However, outcomes of visual analytics are often difficult to quantify, which emphasises precision and reproducibility, especially for research on human diseases. Here, we propose a workflow combining a reproducible computational environment with a dedicated visualisation functionality for systems biology diagrams. By linking the Galaxy with the MINERVA Platform, we visualise and explore COVID-19 transcriptomic data to demonstrate the utility of our workflow. Visualised data recapitulate findings of the original publication and offer new insights about the COVID-19 pathology. Our results offer a blueprint for quick prototyping of computational workflows that facilitate communication and exploration of complex data in biomedical research.

Background and Objectives: The purpose of the study was to analyze the relationships between several clinical and biological factors, but also the tumor topography and surgical strategies used in patients with colorectal cancer. Materials and Methods: We designed an analytical, observational, retrospective study that included patients admitted to our emergency surgical department and diagnosed with colorectal cancer. The study group inclusion criteria were: patients admitted during 2020-2022; patients diagnosed with colorectal cancer (including the ileocecal valve); patients who benefited from a surgical procedure, either in emergency or elective. Results: In our study group, consisting of 153 patients, we accounted for 56.9% male patients and 43.1% female patients. The most common clinical manifestations were pain (73.2% of the study group), followed by abdominal distension (69.3% of the study group) and absence of intestinal transit (38.6% of the study group). A number of 69 patients were operated in emergency (45.1%), while 84 patients (54.9%) benefited from elective surgery. The most frequent topography of the tumor was the sigmoid colon, with 19.60% of the patients, followed by the colorectal junction, with 15.68% of the patients and superior rectum and inferior rectum, with 11.11% of the patients in each subcategory. The most frequent type of procedure was right hemicolectomy (21.6% of the study group), followed by rectosigmoid resection (20.9% of the study group). The surgical procedure was finished by performing an anastomosis in 49% of the patients, an ostomy in 43.1% of the patients, while for 7.8% of the patients, a tumoral biopsy was performed. Conclusions: Colorectal cancer remains one of the most frequent cancers in the world, with a heavy burden that involves high mortality, alterations in the quality of life of the patients and their families, and also the financial costs of the medical systems.

When generalized noncommutative Heisenberg algebra accommodating impacts of finite gravitational fields as specified by loop quantum gravity, doubly–special relativity, and string theory, for instance, is thoughtfully applied to the eight-dimensional manifold (M8), the generalization of the Riemannian manifold becomes imminent. By constructing the deformed affine connections on a four-dimensional Riemannian manifold, we have determined the minimal length deformation of Riemann curvature tensor and its contractions, the Ricci curvature tensor, and Ricci scalar. Consequently, we have been able to construct the deformed Einstein tensor. As in Einstein’s classical theory of general relativity, we have proved that the covariant derivative of the deformed Einstein tensor vanishes, as well. We conclude that the minimal length correction suggests a correction to the spacetime curvature which is manifest in the additional curvature terms of the corrected Riemann tensor and its contractions. Accordingly, the spacetime curvature endows additional curvature and geometrical structure.

The aim of this study was to investigate the relationship between postprandial glycemic levels based on flash-monitoring and the production of intestinal hydrogen (H2) and methane (CH4) gases based on measurement of the amount of these gases in exhaled air. We studied 14 subjects with type 2 diabetes mellitus (T2DM) and 10 individuals without diabetes (control) with 3 food-load tests with simultaneous determination of gases in exhaled air and assessment of glucose levels. In 15.4% of patients with T2DM, there was a non-significant increase in exhaled H2. How-ever, all subjects in the control group had significant increase in exhaled H2. Moreover, the level of H2 in exhaled breathafter food load in patients with T2DM was lower than in normoglycemic subjects. Also, in normoglycemic subjects there was an inverse correlation between maximum glucose rise and maximum H2 in exhaled air after food load. At the same time in patients with T2DM the level of CH4 in exhaled air directly correlated with the parameters of postprandial glycemia in the test with lactulose. Confirmation of a causal relationship between decreased H2 production, increased intestinal CH4 production, and more severe postprandial glycemia may identify new therapeutic targets in the correction of postprandial glycemia in patients with T2DM.

Opossums, native to the Americas, are unique marsupials with over 100 species. The Common Opossum and Virginia Opossum are notable species. They are nocturnal, omnivorous, and adapt to various habitats. Their reproduction involves a short gestation and marsupial pouch development. Despite their ecological benefits like seed dispersal and insect control, their proximity to human habitats exposes them to pathogens, posing public health risks. These include protozoa, helminths, and arthropods that can spread zoonotic parasites and vector-borne diseases. The marsupial immune system, including opossums, is complex, rivaling eutherian mammals. Key immune genes were identified in the grey short-tailed opossum genome. CD1 protein and VpreB surrogate light chain were also found. Marsupials are proposed as ideal models for studying developmental immunology. A West Indian opossum (Didelphis marsupialis) was found and examined. Blood tests revealed abnormalities, including a low white blood cell count and signs of anemia. The results contribute to understanding the species’ health and adaptability in the wild.

Ovarian cancer (OC) represents a significant challenge in the realm of gynecological cancers, characterized by poor survival rates and complex etiology. In this review, we delve into the se-lected genetic, environmental, and hormonal factors underpinning OC development. We have reviewed scientific databases searching for ovarian cancer genetic and epigenetic factors. We have included studies based on their relevancy. As a result of exploring ovarian carcinogen-esis, this systematic review contains data collected from 126 various works. The role of prominent genetic players such as BRCA mutations, DNA repair mechanisms, un-derscores the intricate landscape of OC susceptibility. We explore Li-Fraumeni and Lynch syn-drome, which impart a heightened predisposition to OC development. Hormonal factors such as estrogen, progesterone, and androgens are also discussed. Environmental alterations, ranging from lifestyle influences on OC to microbiome dysbiosis and lifestyle factors such as obesity, al-cohol consumption, and physical activity intersect with genetic and epigenetic pathways, shaping the risk landscape for OC. Through a meticulous examination of current literature, this review provides a nuanced under-standing of the multifactorial nature of OC, emphasizing the need for holistic approaches to prevention, diagnosis, and treatment.

Despite the recent availability of immune checkpoint inhibitors, not all patients affected by Non-Small Cell Lung Cancer (NSCLC) benefit from immunotherapy. The reason for this variability relies to a variety of factors which may allow the identification of novel biomarkers. Presently, a variety of biomarkers are under investigation, including the PD1/PDL1 axis, the tumor mutational burden, and the Microbiota. This latter is made by all bacteria and other microorganisms hosted in our body. The gut microbiota is the most represented and has been involved in different physiological and pathological events, including cancer. In this light, it appears that all conditions modifying gut microbiota can influence cancer, its treatment, and its treatment-related toxicities. The aim of this review is to analyze all conditions influencing the gut microbiota and, therefore, affecting response to immunotherapy, iRAEs and their management in NSCLC patients. The investigation of the landscape of these biological events can allow novel insights for optimal management of NSCLC immunotherapy.

Background and Objectives: In recent years Electronic scooters (E-Scooters) have gained popularity, whether for private use or as a publicly available transportation method. With introduction of these vehicles, reports of E-Scooter related accidents have surged, sparking a public debate and concern. Aim of this study was to analyse epidemiological data, characteristics and severity of traumatic brain injury (TBI) related to E-Scooter accidents. Materials and Methods: This retrospective case series evaluated 28 patients who were admitted to three largest neurosurgery clinics in Riga, Latvia between time period from April to October in two separate years – 2022 and 2023 after an E-Scooter related accident. Data were collected on patient demographics, time of the accident, alcohol consumption, helmet use, type of TBI, other related injuries, treatment and assessment at discharge. Results: A total of 28 patients were admitted with TBI related to E-Scooter use, with median age 30 years (Q1-Q3, 20.25-37.25), four individuals under age of 18, majority (64%) were male. In 23 cases the injury mechanism was fall, in 5 cases collision. None were wearing a helmet at time of injury. Alcohol intoxication was evident in over half of the patients (51.5%), with severe intoxication (&gt;1.2ppm) in 75% cases among them. Neurological symptoms upon admission were noted in 50% of cases. All patients had intracranial trauma - 50% brain contusions, 43% traumatic subdural hematoma, almost 30% - epidural hematoma. Craniofacial fractures were evident in 71% of cases, fractures in other parts of body in 3 patients. 6 patients required emergency neurosurgical intervention. Neurological complications were noted in 2 patients, 1 patient died. Conclusions: E-Scooter related accidents result in a significant number of brain and other associated injuries, with notable frequency linked to alcohol influence and lack of helmet use. Prevention campaigns to raise awareness of potential risks and implementation of more strict regulations should be done.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

The observation that certain therapeutic strategies for targeting inflammation benefit patients with distinct immune-mediated inflammatory diseases (IMIDs) is exemplified by the success of TNF blockade in conditions including rheumatoid arthritis, ulcerative colitis and skin psoriasis, albeit only for subsets of individuals with each condition. This suggests intersecting "nodes" in inflammatory networks at a molecular and cellular level may drive and/or maintain IMIDs, being “shared” between traditionally distinct diagnoses without mapping neatly to a single clinical phenotype. In line with this proposition, integrative tumour tissue analyses in oncology have highlighted novel cell states acting across diverse cancers, with important implications for precision medicine. Drawing upon advances in the oncology field, this narrative review will first summarise learnings from the Human Cell Atlas in health as a platform for interrogating IMID tissues. It will then review cross-disease studies to date that inform this endeavour, before considering future directions in the field.

Background. During the COVID-19 pandemic, there was an increased number of the hospitalized COVID-19 positive patients suffering from type 2 diabetes mellitus (T2DM). The objective of this research was to explore factors associated with the length of hospitalization of patients with T2DM and mild form of COVID-19. Material and Methods. This retrospective cohort study involved all patients who tested positive for COVID-19 and were treated in the dedicated COVID department of the University Clinical Center (UCC) in Nis between September 10, 2021, and December 31, 2021. Upon admission, patients underwent blood tests for biochemical analysis, including blood count, kidney and liver function parameters (C-reactive protein-CRP, creatinine kinase, D-dimer), as well as glycemia and HbA1c assessments. Additionally, all patients underwent lung radiography. Univariate and multivariate regression analyses were employed to assess the impact of specific factors on the length of hospitalization among patients with T2DM. Results. Out of the total 549 COVID-19 positive patients treated, 124 (21.0%) had T2DM, while 470 (79.0%) did not have diabetes. Among patients with T2DM, men were significantly younger than women (60.6±16.8 vs. 64.2±15.3, p

Kinesiophobia (fear of movement) has been recognized as a significant barrier to recovery and rehabilitation in patients after total knee arthroplasty (TKA). Our goal was to identify predictors of kinesiophobia and examine its correlation with early functional outcomes in TKA recipients. On the first and fifth postoperative days (POD1 and POD5), we evaluated pain using the International Pain Outcomes Questionnaire (IPO-Q) and created multidimensional pain composite scores (PCS). Pain Composite Score-total (PCStotal) assesses the overall impact of pain, taking into account outcomes of pain intensity, pain-related interference with function, and emotions and side effects. Functional status on POD 5 was determined by the Barthel index, 6-minute walking test, and knee range of motion. Kinesiophobia was measured on POD5 using the Tampa Scale for Kinesiophobia (TSK) and multivariable logistic regression was used to assess factors associated with kinesiophobia. Among 75 TKA patients, 27% exhibited kinesiophobia. The final regression model highlighted PCStotal on POD5 (OR=6.2, CI=1.9-19.9), PCStotal (OR=2.1, CI=1.2-3.8) on POD1, and the intensity of chronic pain before surgery (OR=1.4, CI=1.1-2.1) as significant kinesiophobia predictors. On POD5, those with kinesiophobia showed increased dependency, slower gait, and poorer knee extension recovery. This study highlights the importance of identifying and addressing kinesiophobia in TKA patients to optimize functional outcomes and improve recovery. Also, it is important to assess not only pain intensity but also the physical and emotional interference caused by pain, which can contribute to the development of kinesiophobia.

Extracellular vesicles (EVs) hold enormous potential in the diagnosis and treatment of diseases, benefit from their roles in intercellular signaling, as well as their plentiful presence and stability in body fluids. However, conventional EV isolation methods are labor-intensive, and harvest EVs with low purity and compromised recovery. In addition, the drawbacks, such as limited sensitivity and specificity of traditional EV analysis methods hinder the application of EVs in clinical use. Therefore, it is urgent to develop effective and standardized methods for isolating and detecting EVs. Microfluidics technology is a powerful and rapidly developing technology that has been introduced as a potential solution for the above bottlenecks. It holds the advantages of high integration, short analysis time, low consumption of samples and reagents. In this review, we summarize the traditional techniques alongside microfluidic-based methodologies for the isolation and detection of EVs. We emphasize the separation advantages of microfluidic technology in enhancing EV capture efficiency and precise targeting, while summarizing its analytical role in targeted detection and discussing the significance of EV detection in the tumor microenvironment, providing a direction for achieving automated and high-throughput EV detection in clinical samples.

Background: The purpose of this review is to clarify the natural course of Benign Paroxysmal Torticollis (BPT) and to update the relationship of this disorder with migraine. BPT belongs to a group of “episodic syndromes that may be associated with migraine” and is diagnosed when according to diagnostic criteria of the International Classification of Headache Disorders, 3rd edition. It is present in infants and young children and it is an underdiagnosed manifestation, because it is not well recognized and in most cases with a benign evolution, but requires careful differential diagnosis. It was first described by Snyder in 1969 as a movement disorder, a cervical dystonia consequent to labyrinthic disorder.Materials and methods: The PubMed and Web of Science databases were consulted from 1968 to 2024, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines ,2020.( PRISMA)Results: 113 articles were identified, 86 selected and 20 considered for the purpose of this review. The clinical studies were considered in relation to evolution, cognitive and motor development, to genetic and not genetic etiology, to the relationship with migraine with and without aura, vestibular migraine, hemiplegic migraine, and paroxysmal vertigo.

To identify factors associated with interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) and build an algorithm to better define this association, for a personalized application in clinical practice. Methods. 78 SSc patients underwent HRCT to assess ILD. Demographic, clinical and laboratory variables were collected, focusing on those associated either directly or indirectly with lung involvement. The discriminant value of each variable was determined using the operating characteristic curves (ROC) and included in a model to estimate the strength of ILD association in SSc. Results. Thirty-three (42.31%) patients showed ILD on HRCT. DLco, M-Borg, GERD-Q, and capillary density were significantly associated with the presence of ILD-SSc. A model including these variables had a coefficient of determination (R2) of 0.697. DLco had an AUC of 0.861 (p&lt;0.001) with a cut-off ≤72.3% (sensitivity 78.8%, specificity 91.1%, +LR 8.86). The m-Borg scale showed an AUC of 0.883 (p&lt;0.001) with a cut-off &gt;2 (sensitivity 84.8%, specificity 82.2%, +LR 4.77), GERD-Q had an AUC of 0.815 (p&lt;0.001) with a cut-off &gt;7 (sensitivity 72.7%, specificity 86.7%, +LR 5.45). The capillary density showed an AUC of 0.815 (p&lt;0.001) with a cut-off ≤4.78 (sensitivity 87.9%, specificity 68.9%, +LR 2.82). Based on the pre-test probability values, these four variables were applied to Fagan's nomogram to calculate the post-test probability of this association. Conclusions. Our study identified four associated clinical factors of ILD in SSc patients. Moreover, their inclusion in an algorithm for the post-test probability, tailored to the specific patients’ characteristics, significantly increases the ability to find out the presence of SSc-ILD.

In line with Pomeau’s conjecture about the relevance of directed percolation (DP) to turbulence onset/decay in wall-bounded flows, we propose a minimal stochastic model dedicated to the interpretation of the spatially intermittent regimes observed in channel flow before its return to laminar flow. Numerical simulations show that a regime with bands obliquely drifting in two stream-wise symmetrical directions bifurcates into an asymmetrical regime, before ultimately decaying to laminar flow. The model is expressed in terms of a probabilistic cellular automaton evolving von Neumann neighbourhoods with probabilities educed from a close examination of simulation results. It implements band propagation and the two main local processes: longitudinal splitting involving bands with the same orientation, and transversal splitting giving birth to a daughter band with orientation opposite to that of its mother. The ultimate decay stage observed to display one-dimensional DP properties in a two-dimensional geometry is interpreted as resulting from the irrelevance of lateral spreading in the single-orientation regime. The model also reproduces the bifurcation restoring the symmetry upon variation of the probability attached to transversal splitting, which opens the way to a study of the critical properties of that bifurcation, in analogy with thermodynamic phase transitions.

The demographic profile of patients transitioning from chronic kidney disease to renal replacement therapy is changing, with a higher prevalence of aging patients with multiple comorbidities such as diabetes mellitus and heart failure. Cardiovascular disease remains the leading cause of mortality in this population, exacerbated by the cardiovascular stress imposed by the HD procedure. The first year after transitioning to hemodialysis is associated with increased risks of hospitalization and mortality, particularly within the first 90–120 days, with greater vulnerability observed among the elderly. This review, based on data from clinics of Fresenius Medical Care Europe, Middle East, and Africa NephroCare, aims to optimize hemodialysis procedures to reduce mortality risk in stable incident and prevalent patients. It addresses critical aspects such as treatment duration, frequency, choice of dialysis membrane, dialysate composition, blood and dialysate flow rates, electrolyte composition, temperature control, target weight management, dialysis adequacy, and additional protocols, with a focus on mitigating prevalent intradialytic complications, particularly intradialytic hypotension prevention.

The KOSovan Acute Coronary Syndrome (KOS-ACS) Registry is established as a prospective, continuous, nationwide, web-based registry that is operated online. The KOS-ACS registry is designed with the following objectives: 1) to obtain data on the demographic, clinical, and laboratory characteristics of ACS patients treated in Kosovo; 2) to create a national database with information on health care in ACS patients treated in Kosovo; 3) to identify the national features of associations between ACS characteristics and clinical outcomes, including mortality, complications, length of hospital stay, and quality of clinical care; and 4) to propose a practical guide for improving the quality and efficiency of ACS treatment in Kosovo. The Kosovo Society of Cardiology and University of Prishtina will be responsible for the development of the KOS-ACS registry and centralized data analysis at the national level. The KOS-ACS Registry will enroll all patients admitted, at any of the registered clinical centers, with the diagnosis of ACS and who will be clinically managed at any of the Kosovo hospitals. Data on patient demographics, clinical characteristics, previous and hospital drug treatment, and reperfusion therapy will be collected. The type of ACS (Unstable angina, NSTEMI or STEMI) will also be clearly defined. The time from first medical contact to balloon inflation (FMC-to-balloon) and door-to-ballon time will be registered. In-hospital death and complications will be registered. Data on post-hospital primary outcome (MACE: cardiac death, all-cause mortality, hospitalization, stroke, need for coronary revascularization) of patients, at 30 days and 1 year, will be included in the Registry.

This article presents the analysis of the allocation of important plant areas (IPA), which urgently identifies the most valuable sites for protecting plant objects. The study is based on a comprehensive inventory of the species composition of plants in the flora of the Western Karatau Ridge and the Mangyshlak Peninsula (arid regions)- key sites Akmysh, Samal, and Kogez, considered standard and the best preserved with natural vegetation cover. The flora of these critical sites was analysed using a combination of field surveys, herbarium studies, and a literature review. The results revealed a rich biodiversity, with 104 species from 82 genera and 33 families. Most species belong to 9 families, making up 60.6% of the total taxa. By the nature of life forms, perennial herbaceous plants dominate in all key sites (30 species, 50.0%). The eco-phylogenetic spectrum showed that a significant share of the flora of the studied IPAs is made up of xerophytes (21 species, 35%) and xeromesophytes (9 species, 15%); desert and mountain-steppe species prevail (53.0%). Rare, endangered and Red Book species account for 10-21.3% of those growing in the region. Regarding economic value, fodder, ornamental, honey, medicinal and food species dominate. The Shannon, Simpson, and Jaccard indices assessed alpha-beta and gamma diversity. The index showed that biodiversity in the Samal and Kogez sites is higher and more evenly distributed compared to the Akmysh site. The Whittaker, Harrison and Cody indices confirm significant differences in the species composition between the sites. In light of these compelling results, a clear and urgent call to action is proposed to allocate these areas to the IPA category, a crucial step towards ensuring the long-term existence of natural biocenoses.

Recent years have been abundant in research concerning human microbiome and its impact on the host’s health. Studies have shown, that not only the commensal bacteria itself, but also postbiotics, understood as unalived microorganisms, possibly with the presence of their components, may have themselves effect on various elements of human physiology. In this article we take a closer look on the specific ways in which postbiotics can alter immune response in allergic asthma, which is one of the most prevalent allergic diseases in today’s world being a serious subject of concern. Through altering patients’ immune response, not only to allergens but also to pathogens, postbiotics could have a significant role in lowering the number of asthma exacerbations. We suggest that more profound research should be undertaken in order to launch postbiotics into clinical standards of asthma treatment, given greatly promising findings in the field of their immunomodulating potential.

To explore the relevant factors that affect the efficacy of consciousness-regaining therapy (CRT)for prolonged disorder of consciousness(pDOC),a retrospective analysis was conducted on the case data of 114 patients with pDOC admitted to department of functional neurosurgery of Tianjin Huanhu Hospital from January 2019 to January 2022. Basic information on the cases,data on pDOC disease assessment, consciousness-regaining therapy methods, and efficacy evaluation were collected. A total of 114 patients were grouped and compared based on the efficacy at the end of treatment. Among them, there were 61 cases in the ineffective group and 53 cases in the effective group. There was no statistically significant difference (P&gt;0.05) between the two groups in terms of gender, age, etiology, acute cerebral herniation, emergency craniotomy surgery, emergency decompressive craniectomy, time from onset to start of consciousness-regaining therapy , and duration of consciousness-regaining therapy(P&gt;0.05). However, there were statistically significant differences (P&lt;0.05) in terms of secondary hydrocephalus, , consciousness-regaining therapy methods, CRS-R grading before treatment, and GOSE score at 6 months after treatment. Binary logistic regression analysis showed that the type of therapy (OR=0.169, 95% CI: 0.057-0.508) was a related factor affecting the efficacy of consciousness-regaining therapy (P&lt;0.05).Compared with non-invasive therapy, personalized awakening therapy using various invasive consciousness-regaining therapy methods can help improve the efficacy of therapy for pDOC.

This study aimed to investigate the appearance and frequencies of the booroola polymorphism of the bone morphogenetic protein receptor 1b (BMPR1B) gene (FecB) and the embrapa polymorphism of the growth differentiation factor 9 (GDF9) gene (FecGE) in sheep in Thailand. A total of 454 cross-bred sheep blood samples were collected from four provinces in Thailand during August 2022 to July 2023. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the FecB and FecGE genotype. The history of ewe birth types was collected from the owners to analyze the association between Fecundity (Fec) genotypes and the history of birth types. The genotypic frequencies of FecB for homozygous genotype (B/B), heterozygous genotype (+/B) and wild-type (+/+) were 0.22%, 1.54%, and 98.24%, respectively. Meanwhile, the genotypic frequencies of FecGE for homozygous genotype (E/E), heterozygous genotype (+/E), and wildtype (+/+) were 0.00%, 2.42%, and 97.58%, respectively. Furthermore, three ewes exhibited both FecB and FecGE genotypes. Fisher’s exact test revealed that the possessor of FecB genotype was associated with multiple births (p&lt;0.01). Both FecB and FecGE mutations were identified in crossbred sheep in Thailand. Sheep containing FecB allele is a better candidate to be selected to improve the prolificacy of crossbred sheep in Thailand.

{Here, we propose a new tool to estimate the complexity of a time series: the entropy of difference (ED). The method is based solely on the sign of the difference between neighbouring values in a time series. This makes it possible to describe the signal as efficiently as prior proposed parameters such as permutation entropy (PE) or modified permutation entropy (mPE), but (1) reduces the size of the sample that is necessary to estimate the parameter value, and (2) enables the use of the Kullback-Leibler divergence to estimate the "distance" between the time series data and random signals.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron and over time the cystic dilatation lead to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts lead to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and haematuria. However, the presentation of ADPKD varies in children from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset of ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide the clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra normal kidney function we explored the glomerular filtration rates dynamics and the renal ultrasound adjusted percentiles. 14 out of 16 patients had kidney percentile over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 ml/min/1.73m2 compared to Schwartz eGFR 126.28 ± 33.07ml/min/1.73m2, p=0.14). Also, when the quadratic equation was employed, not even a patient reached the glomerular hyperfiltration thresholds. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1-year of follow-up (Quadratic ΔeGFR=0.32±5.78ml/min/1.73m2) as opposed to Schwartz formula that can falsely classify children in a hyperfiltration state ΔeGFR=7.51±19.46ml/min/1.73m2), p=0.019.

In Cameroon, Aedes mosquitoes transmit various arboviruses, posing significant health risks. We aimed to characterize the Aedes virome in southwestern Cameroon and identify potential core viruses which might be associated with vector competence. A total of 398 Aedes mosquitoes were collected from four locations (Bafoussam, Buea, Edea and Yaounde). Aedes albopictus dominated all sites except for Bafoussam where Aedes africanus prevailed. Metagenomic analyses of mosquitoes grouped per species into 54 pools revealed notable differences in eukaryotic viromes between Ae. africanus and Ae. albopictus, with the former exhibiting greater richness and diversity. Thirty-seven eukaryotic virus species from 16 families were identified, including six novel viruses with near complete genome sequences. Seven viruses were further quantified in individual mosquitoes via qRT-PCR. Although none of them could be identified as core viruses, Guangzhou sobemo-like virus and Bafoussam mosquito solemovirus virus were highly prevalent regionally in Ae. albopictus and Ae. africanus, respectively. This study highlights the diverse eukaryotic virome of Aedes species in southwestern Cameroon. Despite their shared Genus, Aedes species exhibit limited viral sharing, with varying viral abundance and prevalence across locations. Ae. africanus, an understudied vector, harbors a rich and diverse virome, suggesting potential implications for arbovirus vector competence.

Abstract A multiple number of studies provide evidence that vasopressin (AVP) and steroid hormones are frequently secreted together and closely cooperate in the regulation of blood pressure, metabolism, water-electrolyte balance, and behavior, securing thereby survival and comfort of life. Vasopressin interacts with hormones of the hypothalamo-pituitary-adrenal axis (HPA) at several levels through regulation of release of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone ACTH, and multiple steroid hormones, as well as through interactions with steroids in the target organs. The interactions are facilitated by positive and negative feedbacks occurring between specific components of the HPA axis with engagement of other regulatory molecules. Altogether AVP and HPA cooperate closely as a coordinated functional AVP-HPA system. It has been shown that cooperation between AVP and steroid hormones may be affected by the cellular stress combined with hypoxia, and by metabolic, cardiovascular and respiratory disorders, neurogenic stress and inflammation. Growing evidence indicates that central and peripheral interactions of AVP and steroid hormones are reprogrammed in cardiovascular diseases and that the rearrangements play either beneficial or harmful effects. The present review highlights specific mechanisms of interactions of AVP and steroids at cellular and systemic levels and analyses consequences of inappropriate cooperation between various components of the AVP-HPA system for the regulation of the cardiovascular system and energy balance in cardiovascular and metabolic diseases.

Signal preprocessing and feature extraction are two important and necessary steps of data analysis. In signal analysis, typically these two steps are implemented through multiple algorithms. Moreover, the significant parameters in most algorithms are set empirically. We have developed an algorithm that can preserve and highlight characteristic waveforms while attenuating non-feature waveforms. The parameters in the algorithm are set through difference analysis. We have conducted experiments on both clinical and open-source ECG data, obtaining effective test results.

Opuntia ficus-indica (L.) Mill. belongs to the Cactaceae family and the genus Opuntia; it is a succulent plant that adapts to extreme climatic conditions. The aerial part of the plant consists of the cladodes, morphological changes of branches that appear green, are covered with thorns, and are essential to reduce excessive perspiration of water. The composition of cladodes is very varied, and the main constituents are water, fibers, polysaccharides, proteins, fatty acids, vitamins, sterols, minerals, and polyphenols. Polyphenols are responsible for many beneficial activities for human health, such as antioxidant, anti-inflammatory, antitumor, and nutritional properties. The purpose of this manuscript was to compare the properties of cladodes belonging to the same plant but with different stages of maturity. Relative extracts were tested both in vitro and on a cell line and antioxidant and anti-apoptotic properties were found. The antioxidant activity was tested by the ORAC test, the DPPH test, and the measurement of cellular accumulation of ROS. Anti-apoptotic activity was evaluated by the annexin/PI assay and measurement of caspases 9 and 3 expression. The results obtained have shown that the extracts considered possess antioxidant and anti-apoptotic properties. However, the different stages of maturity of cladodes are essential for the performance of both functions. In addition, important variations have been made in the dissolution of extracts that have brought greater safety in their use. In conclusion, this manuscript provides further information on cladodes of Opuntia ficus-indica, which can be used as adjuvants in many human pathologies.

Boundary behavior of a given important function or its limit values are essential in the whole spectrum of mathematics and science. We consider some tractable cases of limit values in which either a difference of two ingredients or a difference equation is used coupled with the relevant functional equations to give rise to unexpected results. This involves the expression for the Laurent coefficients including the residue, the Kronecker limit formulas and higher order coefficients as well as the difference formed to cancel the inaccessible part, typically the Clausen functions. We also state Abelian results which yield asymptotic formulas for weighted summatory function from that for the original summatory function

Determining the genetic contribution of susceptibility to severe SARS-CoV-2 infection outcomes is important for public health measures and individualized treatment. Through intense research on this topic, several hundred genes have been implicated as possibly contributing to the severe infection phenotype(s); however, the findings are complex and appear to be population-dependent. We aimed to determine the contribution of human rare genetic variants associated with a severe outcome of SARS-CoV-2 infections and their burden in the Slovenian population. A panel of 517 genes associated with severe SARS-CoV-2 infection were obtained through an extensive review of the literature, and additionally included target genes identified by the COVID-19 Host Genetic Initiative, as well as the curated Research COVID-19 associated genes from PanelApp, England Genomics. Whole genome sequencing was performed using PCR-free WGS on DNA from 60 patients hospitalized due to severe COVID-19 disease, and the identified rare genomic variants were analyzed and classified according to the ACMG criteria. Background prevalence in the general Slovenian population was determined by comparison with sequencing data from 8025 individuals included in the Slovenian genomic database (SGDB). Results show that several rare pathogenic/likely pathogenic genomic variants in genes CFTR, MASP2, MEFV, TNFRSF13B, and RNASEL likely contribute to the severe infection outcomes in our patient cohort. These results represent an insight into the Slovenian genomic diversity associated with severe COVID-19 outcome.

In this work, we experimentally investigate mass and heat transport phenomena in a modular device while converting a solution salinity difference into a temperature difference. Operations occur under fixed total ambient pressure and without mechanical moving parts, thus realizing a fully static conversion. Provided that a constant salinity gradient can be imposed, the proposed device is able to generate a steady cooling capacity. Here, we purposely operate with environmentally benign and easily accessible sodium chloride water solutions only. A numerical model is finally elaborated, validated and used to explore a wider range of possible device configurations and operating conditions.

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.

The most common type of head and neck cancer (HNC) is head and neck squamous cell carcinoma (HNSCC). It describes a heterogenous neoplastic disease that arises from the mucosal epithelium of the of the upper respiratory system and the gastrointestinal tract. It is characterized by high morbidity and mortality, being is the eighth most common cancer worldwide, with 931,931 newly diagnosed cases and 467,125 deaths according to the latest Global Cancer Statistics (GLOBOCAN) data. Despite the use of modern low-invasive surgical techniques and application of promising new chemoradiotherapies or combination treatment, the frequency of recurrences and the five-year survival of these patients remains unsatisfactory. The microenvironment of head and neck cancer comprises various cells that regulate neoplastic expansion. It is believed that the mesenchymal stromal cells (MSCs) present in the tumour milieu play a key role in the modulation of tumour initiation, development and progression, in the regulation of cancer treatment response, survival rates, patient outcomes and long-term prognosis; they also influence the resistance to cisplatin-based chemotherapy, the gold standard for advanced HNSCC. MSCs, are multipotent, heterogeneous, mobile cells, which meet specific stemness criteria defined by the International Society for Cellular Therapy (ISCT). Although no MSC-specific markers exist, they can be recognized based on several others, such as CD73, CD90 and CD105, while lacking the presence of CD45, CD34, CD14 or CD11b, CD79α, or CD19 and HLA-DR antigens; they share phenotypic similarity with stromal cells and their capacity to differentiate into other cell types. In the tumour niche, MSC populations are characterized by cell quiescence, self-renewal capacity, low reactive oxygen species production and the acquisition of epithelial-to-mesenchymal transition properties, they may play a key role in the process of acquiring drug resistance, and thus treatment failure. MSCs must also demonstrate plastic adherence in vitro and be able to differentiate into specific mesodermal cell types after stimulation i.e., adipocytes, chondrocytes, and osteoblasts when cultured under well-defined conditions. The present narrative review examines the links between mesenchymal stromal/stem cells and HNC, as well as the different mechanisms involved in the development of resistance to current chemo- and radiotherapies in HNSCC. It provides an overview of the current literature, including key opinion-forming systematic reviews, as well as cross-sectional, longitudinal, prospective and interventional studies based on cell culture models in vitro, animal or in vivo models of HNSCC; it also examines the possibilities of pharmacological targeting of stemness-related chemoresistance in HNSCC. It describes promising new strategies to optimize chemoradiotherapy with the potential to personalize patient treatment approaches, and highlights future therapeutic perspectives in HNC. The data concerning tumour-associated MSCs is arranged according to increasing clinical credibility.

When the minimal length approach emerging from noncommutative Heisenberg algebra, generalized uncertainty principle (GUP), and thereby integrating gravitational fields to this fundamental theory of quantum mechanics (QM) is thoughtfully extended to Einstein field equations, the possible deformation of the metric tensor could be suggested. This is a complementary term combining the effects of QM and general relativity (GR) and comprising noncommutative algebra together with maximal spacelike four–acceleration. This deformation compiles with GR as curvature in relativistic eight–dimensional spacetime tangent bundle, generalization of Riemannian spacetime, is the recipe applied to derive the deformed metric tensor. This dictates how the affine connection on Riemannian manifold is straightforwardly deformed. We have discussed the symmetric property of deformed metric tensor and affine connection. Also, we have evaluated the dependence of a parallel transported tangent vector on the spacelike four–acceleration given in units of L, where L = rℏcG3 is a universal constant, c is speed of light, and ℏ is Planck constant, and G is Newton’s gravitational constant.

Cortical actomyosin flows, among other mechanisms, scale up spontaneous symmetry breaking and thus play pivotal roles in cell differentiation, division, and motility. According to many model systems, myosin motor-induced local contractions of initially isotropic actomyosin cortices are nucleation points for generating cortical flows. However, the positive feedback mechanisms by which spontaneous contractions can be amplified towards large-scale directed flows remain mostly speculative. To investigate such a process on spherical surfaces, we reconstituted and confined initially isotropic minimal actomyosin cortices to the interfaces of emulsion droplets. The presence of ATP leads to myosin-induced local contractions that self-organize and amplify into directed, large-scale actomyosin flows. By combining our experiments with theory, we found that the feedback mechanism leading to a coordinated, directional motion of actomyosin clusters can be described as asymmetric cluster vibrations, caused by intrinsic non-isotropic ATP consumption, in conjunction with spatial confinement. By tracking individual actomyosin clusters, we identified fingerprints of vibrational states as the basis of directed motions. These vibrations may represent a generic key driver of directed actomyosin flows under spatial confinement in vitro and in living systems.

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.

In Pakistan, 2018 National Nutrition Survey reported 40% of under five children were stunted. This study assesses the effectiveness of nutritional supplementation in reducing stunting among under-five children in two rural districts in Sindh, Pakistan. This was a mixed-method quasi-experimental study with intervention and control population. 3397 and 3277 under-five children participated in the baseline and end-line surveys. Both study areas were matched for demographic and economic circumstances. The participants received nutrient supplements underpinned by nutrition behaviour change communication for appropriate complementary feeding practices and hand hygiene targeted at primary caregivers during the first 1000 days of an infant's life. The impact was assessed using the difference in difference analysis with kernel propensity score matching to adjust the differences among control and intervention populations.

Nurses have experienced several psychological and work-related issues during the COVID-19 pandemic including pandemic burnout and job burnout. The aim of the study was to examine the impact of social support and resilience on COVID-19 pandemic burnout and job burnout among nurses. We conducted a cross-sectional study in Greece. Study population included 963 nurses. We measured social support, resilience, COVID-19 pandemic burnout, and job burnout with the Multidimensional Scale of Perceived Social Support, Brief Resilience Scale, COVID-19 burnout scale, and single item burnout measure respectively. Nurses received high levels of social support, while their resilience was moderate. Additionally, nurses experienced moderate levels of COVID-19 burnout and job burnout. Increased social support (adjusted beta = -0.075, 95% CI = -0.125 to -0.024) and increased resilience (adjusted beta = -0.399, 95% CI = -0.491 to -0.308) were associated with reduced COVID-19 pandemic burnout. We found a negative relationship between social support and job burnout (adjusted beta = -0.263, 95% CI = -0.405 to -0.121). A similar negative relationship was found between resilience and job burnout (adjusted beta = -0.529, 95% CI = -0.785 to -0.272). Social support and resilience can act as protective factors against COVID-19 pandemic burnout and job burnout among nurses. Policy makers should develop and implement appropriate strategies to improve nurses’ social support and resilience since they are the backbone of healthcare systems worldwide.

Flap surgery is a common method used to cover defects following tumor ablation, trauma, or infection. However, insufficient vascularity in the transferred flap can lead to flap necrosis and failure. Proper postoperative monitoring is essential to prevent these complications. Recently, research has explored the use of infrared thermal imaging in plastic surgery, leading to its clinical application. This study investigates the use of a forward-looking infrared (FLIR) camera to monitor blood flow in flaps. In the study, 28 rats underwent reverse McFarlane flap surgery, and their flaps were analyzed using a FLIR thermal imaging camera seven days post-surgery. Additionally, thermal images of flaps were taken on postoperative days 0, 1, 2, 3, and 7 in 22 patients. The study focused on temperature differences between normal skin and the perforator compared to the average flap temperature. Results showed that the temperature difference was higher in the necrosis group and increased over time in cases of total necrosis. A lower perforator temperature compared to the flap's average indicated vascular compromise, potentially leading to flap failure. The FLIR camera, being contact-free and convenient, shows promise for understanding and inferring the clinical progression of flaps in postoperative monitoring.

Probiotic feed additives have attracted considerable research interest in recent years because the effectiveness of probiotics can differ across microbial strains and the supplemented macroorganisms. The present study was conducted on 16 lambs divided into two groups (C - control and E - experimental). The examined lambs were aged 11 days at the beginning of the experiment and 40 days at the end of the experiment. The diet of group E lambs was supplemented with a multi-strain probiotic formulation (Lactobacillus plantarum AMT14, Lactobacillus plantarum AMT4, Lactobacillus rhamnosus AMT15, and Bifidobacterium animalis AMT30), whereas group C lambs did not receive the probiotic additive. At the beginning of the experiment (day 0) and on experimental days 15 and 30, blood was sampled from the jugular vein to determine and compare: phagocytic activity (PHAGOTEST) and oxidative metabolism (PHAGOBURST) of peripheral blood granulocytes and monocytes by flow cytometry. An analysis of the phagocytic activity of granulocytes and monocytes revealed significantly higher levels of phagocytic activity (expressed as the percentage of phagocytic cells and mean fluorescence intensity) in lambs administered the multi-strain probiotic formulation than in the control group. The probiotic feed additive also exerted a positive effect on the oxidative metabolism of both granulocytes and monocytes (expressed as the percentage of oxidative metabolism and mean fluorescence intensity) after stimulation with Escherichia coli bacteria and with PMA (4-phorbol-12-β-myristate-13-acetate).

Background/Objectives: The aim of this study was to investigate feasibility and safety of neuromuscular electrical stimulation (NMES) in patients on extracorporeal membrane oxygenation (ECMO) and assess thoroughly any potential adverse events. Methods: We conducted a safety and feasibility study including 16 ICU patients on ECMO support who were admitted to the cardiac surgery ICU from January 2022 to December 2023. Patients underwent a 45-minute NMES session, still on ECMO support, that included a warm up phase of 5 minutes, a main phase of 35 minutes and a recovery phase of 5 minutes. NMES was implemented on vastus lateralis, vastus medialis, gastrocnemius and peroneus longus muscle of both lower extremities. Two stimulators delivered biphasic, symmetric impulses of 75 Hz, with 400 μsec pulse duration, 5 sec on (1,6 sec ramp up and 0,8 sec ramp down) and 21 sec off. The intensity levels aimed to cause visible contractions and be well tolerated. Primary outcomes of the study were feasibility and safety, evaluated by whether the NMES sessions were successfully achieved, and by any adverse events and complications. Secondary outcomes included indices of rhabdomyolysis from biochemical blood test, 24 hours after the application of NMES. Results: All patients successfully completed their 45-minute NMES session, without presenting hemodynamic deterioration, adverse events or signs of rhabdomyolysis. The majority of patients achieved type 4 and 5 quality of muscle contraction. Conclusions: NMES is a safe and feasible exercise methodology in patients supported with ECMO.

A phase 1-2, prospective, multicenter, randomized, open-label clinical trial (Code RPCEC00000382, https://rpcec.sld.cu/trials/RPCEC00000382-En/), with parallel groups, involving 1161 participants was designed to assess safety and immunogenicity of two Cuban COVID-19 vaccines (Mambisa and Abdala) in boosting COVID-19 immunity of convalescent adults after receiving one dose of either vaccine. The main safety outcome was severe vaccination adverse events occurring in &lt;5% of vaccinees. Main immunogenicity success endpoints were ≥4-fold anti-RBD IgG seroconversion or ≥20% increase in ACE2-RBD inhibitory antibodies in &gt;55% of vaccinees in Phase 1 and &gt;70% in Phase 2. Neutralizing antibody titers against SARS-CoV-2 variants were evaluated. Both vaccines were safe; no deaths or severe adverse events occurred. Mild intensity adverse events were the most frequent (&gt;73%); headache predominated for both vaccines. Phase 1 responders were 83.3% (p = 0.0018) for Abdala. Mambisa showed similar results. Phase 2 responders were 88.6% for Abdala (p &lt;0.0001) and 74.2% for Mambisa (p = 0.0412). In both phases, anti-RBD IgG titers, inhibition percentages and neutralizing antibody titers increased significantly after the booster dose. Both vaccines were safe and their immunogenicity surpassed the study endpoints.

Background and objective: Analysis of inflammatory biomarkers, along with the neutrophil/lymphocyte ratio (NLR) or platelets/lymphocyte ratio (PLR), supports the connection between inflammation and carcinogenesis. Methods: We conducted a retrospective observational study at the Clinical County Hospital Mureș, including patients with lung cancer. The parameters analyzed included: histopathological type (NSCLC - squamous cell carcinoma or adenocarcinoma; SCLC), molecular mutations (EGFR, ALK, PD-L1), parameters from the complete blood count, inflammatory parameters and associated comorbidities. Results: 380 patients were included: 115 patients in the cancer group and 265 patients in the control group. Among patients in the lung cancer group, 88 were diagnosed with NSCLC (44 adenocarcinomas, 44 squamous cell carcinomas) and 27 with SCLC. Both NLR and PLR were significantly higher in cancer patients than in the control group (5,30 versus 2,60, p&lt;0,001; 217 versus 136, p&lt; 0.001, respectively). NLR and PLR differs between men and women (p = 0.005, respectively p=0.056). C-reactive protein was not correlated with either NLR (p-value: 0.0669) or PLR (p-value: 0.6733) in lung cancer patients. Conclusion: The NLR and PLR values ​​may serve as new predictive biomarkers for the diagnostic of disease in patients with lung cancer, especially those with NSCLC.

Background Neisseria gonorrhoeae can acquire antimicrobial resistance (AMR) through horizontal gene transfer (HGT) from other Neisseria spp. such as commensals like Neisseria subflava. The prevalence of Neisseria subflava in the oropharynx is close to 100%. Low doses of antimicrobials in food could select for AMR in N. subflava, which could then be transferred to N. gonorrhoeae. In this study, we aimed to determine the lowest concentration of ciprofloxacin that can induce ciprofloxacin resistance (minimum selection concentration – MSC) in N. subflava. Methods Neisseria subflava Co000790/2 was serially passaged on GC agar plates containing ciprofloxacin concentrations ranging from 1:100- to 1:10,000-below its ciprofloxacin MIC (0.006 µg/ml) for six days. Results After 6 days of serial passaging at ciprofloxacin concentrations 1/100th of the MIC, 24 colonies emerged on the 0.06 µg/ml ciprofloxacin plate. Their ciprofloxacin MICs were between 0.19 to 0.25 µg/ml, and whole genome sequencing revealed a missense mutation T91I in the gyrA gene, which has previously been found to cause reduced susceptibility to fluoroquinolones. Conclusion The N. subflava MSCde novo was determined to be 0.06 ng/mL or 1:100 below the MIC. The implications of this finding are that the low concentrations of antibiotics found in certain environmental samples and even the food we eat may be able to select for ciprofloxacin resistance in N. subflava.

In recent years, the prevalence of tobacco and electronic cigarette (e-cigarette) use among adolescents has raised significant public health concerns worldwide. This study aims to investigate respiratory symptoms among Polish adolescents. We conducted an online survey among Polish school students from all provinces, collecting data over two months in Spring 2021. Students voluntarily complete the anonymous survey, answering questions about respiratory symptoms, smoking habits (both traditional and electronic cigarettes), and demographic information. Analysis focused on four subgroups: non-tobacco users, traditional cigarette smokers, e-cigarette users, and dual users, totaling 10,388 pupils aged 12-18 years, predominantly attending secondary technical and comprehensive schools. A total of 10388 pupils participated in the study, 55.6 % (5778) of whom were girls and 44.4 % (4610) boys. Adolescents, who admitted using both e-cigarettes and traditional cigarettes experienced more frequent episodes of cough during the day (39.70%) and at night (18.40%) compared to their peers in other groups. Chest discomfort, including pain and pressure, was also reported more often by adolescents, who used e-cigarettes and traditional cigarettes concurrently (27.60%) compared to their peers in other groups. Chest pressure was experienced less commonly by non-smoking adolescents (14.40%) than by smokers (18.90%). Higher severity of cough during the day and at night was observed in the group of adolescents using traditional cigarettes and e-cigarettes concurrently compared to the other groups. The adolescents in the dual user group experienced more severe dyspnoea and wheezing compared to the other groups included in the comparison. The results of this study confirm the correlation between the occurrence of respiratory symptoms in adolescents who smoke cigarettes, use e-cigarettes and in dual users. The respiratory symptoms occur most frequently and are the most severe in the group of adolescents who use e-cigarettes and traditional cigarettes

Workplace bullying is common among nurses affecting negatively several work-related variables, such as job burnout and job satisfaction. However, no study until now has examined the impact of workplace bullying on quiet quitting among nurses. Thus, our aim was to examine the direct effect of workplace bullying on quiet quitting and to investigate the mediating effect of coping strategies on the relationship between workplace bullying and quiet quitting in nurses. We conducted a cross-sectional study with a convenience sample of 650 nurses in Greece. We collected our data during February 2024. We used the Negative Acts Questionnaire-Revised, the Quiet Quitting Scale and the Brief COPE to measure workplace bullying, quiet quitting and coping strategies, respectively. We found that workplace bullying and negative coping strategies were positive predictors of quiet quitting, while positive coping strategies was a negative predictor of quiet quitting. Our mediation analysis showed that positive and negative coping strategies partially mediated the relationship between workplace bullying and quiet quitting. In particular, positive coping strategies caused competitive mediation, while negative coping strategies caused complimentary mediation. Nurses’ managers and policy makers should improve working conditions by reducing workplace bullying and strengthening positive coping strategies among nurses.

A multiscale model that enables quantitative understanding and prediction of the size effect on scattering properties of micro- and nanostructures is crucial for the design of LED surface textures optimized for high light extraction efficiency (LEE). In this paper, a hybrid process for combining full-wave finite-difference time-domain simulation and a ray-tracing technique based on a bidirectional scattering distribution function model is proposed. We apply this method to study the influence of different pattern sizes of a patterned sapphire substrate on GaN-based LED light extraction from the microscale to the nanoscale. The results show that near-wavelength–scaled patterns with strong diffraction are not expected to enhance LEE. By contrast, microscaled patterns with optical diffusion behavior have the highest LEE at a specific aspect ratio, and subwavelength-scaled patterns that have antireflection properties show marked enhancement of LEE for a wide range of aspect ratios.

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.

Mental disorders impact a significant portion of the global population, presenting substantial challenges to healthcare systems due to high hospitalization costs and resource demands. This narrative review explores the economic implications of mental health disorders, focusing on hospitalization costs, the effectiveness of interventions, and the outcomes of recent research. Materials and Methods: A narrative review was conducted, sourcing articles from PubMed and Google Scholar published between 2014 and 2024. The search terms included combinations related to mental illness, costs, hospital care, and mental healthcare interventions. A total of 1,110 articles were initially identified, with 37 studies meeting the inclusion criteria after rigorous screening by two independent researchers. These studies included quantitative and qualitative data covering a range of outcomes such as hospital admission rates, consumer satisfaction, and quality of life. The findings of the present review reveal that mental disorders significantly increase hospitalization costs due to frequent admissions, extended stays, and the need for specialized treatments. Additionally, physical comorbidities in individuals with mental disorders lead to higher healthcare costs and resource use. Integrated care models, early intervention, and preventive strategies show promise in reducing these costs and improving patient outcomes. Conclusions: Our review emphasizes the critical need for integrated healthcare strategies that address both mental and physical health to reduce hospitalization costs and improve outcomes. Effective management of mental health disorders requires comprehensive approaches, including complex outpatient services and preventive care. Future research should focus on standardizing methodologies to provide clearer insights into the economic impact of mental health conditions and guide effective healthcare strategies.

The purpose of this review is to elucidate the actual threat of the most prevalent mycotoxins in agricultural commodities and human/animal food/feed for appearance of foodborne ailments and diseases. The underestimated hazard of joint mycotoxin uptake of animals or humans is critically discussed with regards to synergistic or additive interaction between some target mycotoxins. The real toxicity of target mycotoxin combinations as it happens in practice is evaluated and possible lower limit values or control measures are suggested in such cases. Some critical points in adequate risk assessment, hygiene control and regulation of mycotoxns are discussed. The efficiency of current mycotoxin regulations and control measures is evaluated in regards to human/animal health hazard. The risk assessment in the case of multiple mycotoxin exposure of humans/animals via the food/feed or agricultural commodities is evaluated and some suggestions are proposed in such cases. Appropriate control measures and food safety issues throughout the food supply chain are proposed in order to prevent target foodborne diseases. Some preventive measures and possible veterinary hygiene control or risk assessment are proposed in some practical cases of foodborne diseases for preventing mycotoxin contamination of animal products designed for human consumption and to avoid possible public health issues.

The study of cell-free DNA (cfDNA) and other peripheral blood components (known as “liquid biopsies”) is promising and has been investigated especially in solid tumors. Nevertheless, it is increasingly showing greater utility in the diagnosis, prognosis, and response to treatment of hematological malignancies; in the future, it could prevent invasive techniques, such as bone marrow (BM) biopsy. Most of the studies about this topic have been focused on B cell lymphoid malignancies; some of them have shown that cfDNA can be used as a novel way for diagnosis and minimal residual monitoring in B cell lymphomas, using techniques such as next-generation sequencing (NGS). In myelodysplastic syndromes, multiple myeloma, or chronic lymphocytic leukemia, liquid biopsies may allow for an interesting genomic representation of the tumor clones affecting different lesions (spatial heterogeneity). In acute leukemias, it can be helpful in the monitoring of early treatment response and the prediction of treatment failure. In chronic lymphocytic leukemia, the evaluation of cfDNA permits the definition of clonal evolution and drug resistance in real-time. However, there are limitations such as the difficulty in obtaining sufficient circulating tumor DNA for achieving a high sensitivity to assess minimal residual disease or the lack of standardization of the method and clinical studies to confirm its prognostic impact. This review focuses on clinical applications of cfDNA on minimal residual disease in hematological malignancies.

Bosentan, an endothelin-receptor antagonist (ERA), has potential anti-atherosclerotic properties. We investigated the complementary effects of bosentan and atorvastatin on the progression and composition of the atherosclerotic lesions in diabetic mice. Forty-eight male apoE-/- mice were fed high-fat diet (HFD) for 14 weeks. At week 8, diabetes was induced with streptozotocin and mice were randomized into 4 groups: 1) Control/COG: no intervention. 2) ΒΟG: bosentan 100 mg/kg/day per os. 3) ATG: atorvastatin 20mg/kg/day per os). 4) BO+ATG: Combined administration of bosentan and atorvastatin. The intra-plaque contents of collagen, elastin, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-a (TNF-a), matrix-metalloproteinases (MMP-2,-3,-9), and TIMP-1 concentrations were determined. The percentage of lumen stenosis significantly decreased across all treated groups: BOG: 19.5±2.2%, ATG: 12.8±4.8%, BO+ATG: 9.1±2.7% compared to controls (24.6±4.8%, p&lt;0.001). Both atorvastatin and bosentan significantly increased collagen content and fibrous cap thickness versus COG (p&lt;0.01). All intervention groups reduced the relative intra-plaque concentrations of MCP-1, MMP-3,-9, and increased TIMP-1 compared to COG (p&lt;0.001). Importantly, bosentan showed modest but additive to atorvastatin effects on the latter parameters compared COG (p&lt;0.05). Bosentan treatment in diabetic, atherosclerotic apoE-/- mice delayed the atherosclerosis progression and enhanced plaques’ stability, showing modest but complementary effects with atorvastatin, which are promising in atherosclerotic cardiovascular diseases.

Artificial Intelligence (AI) and Machine Learning (ML) approaches that could learn from large data sources have been identified as useful tools to support clinicians in their decisional process; AI and ML implementations have had a rapid acceleration during the recent COVID-19 pandemic. However, many ML classifiers are “black box” to the final user, since their underlying reasoning process is often obscure. Additionally, the performance of such models suffer from poor generalization ability in presence of dataset shift. Here, we present a comparison between an explainable-by-design (“white box”) model (Bayesian Network (BN)) versus a black-box model (Random Forest), both studied with the aim to support clinicians of Policlinico San Matteo University Hospital in Pavia (Italy) during the triage of COVID-19 patients. Our aim is to evaluate whether the BN predictive performances are comparable with those of a widely used but less explainable ML model such as Random Forest and to test the generalization ability of the ML models across different waves of the pandemic.

The aim of the study was to test the significance of the EPT index in the water quality assessment of three types of water bodies in hilly and mountainous region of Serbia. The aquatic macroinvertebrate community was dominated by the group of insects, of which 95 taxa represent the EPT group. We compared the obtained values of biological indices used for the assessment of water quality according to the national legislation with the overall status assessment represented by the ecological quality classes (EQC). The results of the Spearman correlation test showed a negative correlation of EQC with the EPT index, BMWP score, H', total number of taxa and number of sensitive taxa, while a positive correlation was observed for the values of SI and Tubificinae %. The values of EQC and biological indices were subjected to principal component analysis (PCA). The results showed that the parameters that contributed most to the differences were the EPT index, the BMWP score and the number of sensitive taxa. The results indicate that the EPT index is an excellent indicator of changes in water quality and an important tool for the ecological categorization of water bodies in mountain regions.

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.

Penile cancer (PeCa) is a rare urological malignancy characterized by significant geographic variations in both incidence and mortality rates. Due to its rarity and the consequent lack of randomized trials, current management is based on retrospective studies and small prospective trials. In addition, the diagnostic pathways and treatment strategies exhibit substantial heterogeneity, differing significantly between less developed and well-developed countries. The prognosis of PeCa is determined by the presence and extent of regional lymph node (LN) involvement. Therefore, early detection and treatment of LN metastasis is paramount to ensure better outcomes. In recent decades, the overall survival for PeCa has increased, mainly due to advancements in imaging techniques and risk stratification. We aim to provide an overview of the current role of PET CT imaging in the management of patients with PeCa.

Objectives: To assess the concordance of the preoperative application of the #Enzian classification (#ENZIANi) with the postoperative result (#ENZIANs) using surgical findings as the reference standard. Methods: This retrospective study included 282 consecutive patients with deep endometriosis undergoing surgical treatment. Preoperative assessment with transvaginal sonography and magnetic resonance imaging was compared with postoperative assessment. Concordance and diagnostic test evaluation were calculated. Results: The highest concordance was observed in the F (abdominal wall endometriosis) with k Cohen of 0.837, following the values for pelvic locations, with 0.795 for T left, 0.791 for T right, 0.776 for F (adenomyosis), 0.766 for C (rectum), and 0.75 and 0.72 for O right k and O left, respectively. The highest sensitivity was demonstrated for the P compartment *(98%), T compartment (both sides 97%), and A, B, C (94%- 96%), corresponding with deep endometriosis. Conclusions: Preoperative assessment using TVS/TAS+MRI with the ENZIANi score correlates well with the ENZIANs postoperative score and demonstrates good concordance in the detection and localization of deep endometriosis, thereby minimizing false negative results and ensuring accurate preoperative staging. The ENZIAN classification is well-suited to surgeons&#39; needs and benefits from continuous development. Future improvements, such as adding the expanded C module, may be considered in the next edition.