Two decades after the antiretroviral therapy (ART) introduction, several challenges still prevail in maintaining people living with HIV (PLHIV), even with "Test and Treat" and/or "Rapid Start of ART" initiatives, as well as the scale-up of ART worldwide to promote access and adherence to treatment. This review examined articles on ART adherence in Africa between 2016 and 2023, published in English and indexed in PubMed. A total of 16 articles out of 2415 were eligible and included for analyses. Overall, ART adherence rates in SSA regions ranged from 43% to 84%. Rates in the centre of the SSA region ranged from 58% to 80%, in the north from 50% to 83%, in the south from 77% to 84%, in the west from 43% to 60% and in the east from 69% to 73%. Most African countries use the self-report to assess treatment adherence, although unreliable. The main factors with negative influence on ART adherence were comorbidities, lack of motivation, socioeconomic difficulties or side effects. Conclusion: Adherence to ART is a good indicator for controlling the spread of HIV. It is important to overcome the barriers that make it difficult to comply with ART and reinforce the factors that facilitate the accession of medication.

Tobacco and cannabis use pose major health risks and are major contributors to causes of death worldwide. Mobile phone-based cessation apps for these substances are gaining popularity, often used as a component of traditional interventions. This study aimed to analyze adherence to an intervention using a mobile phone application (App-therapy Prescind) as a function of sociodemographic variables (age, gender, educational level, and profession) as well as the primary activities supported by the app (reducing tobacco or cannabis use and increasing physical exercise). The participants were recruited through the web pages of the Occupational Risk Prevention Service and the Psychology Clinic of the University of Granada during the Covid-19 confinement period. The application’s content includes three components (self-report, motivational phrases, and goal-setting). Our findings indicate that being male, aged between 26 and 62, having a secondary or high school education, and being unemployed increase the likelihood of adherence to the Prescinde App-therapy three months after usage. Our findings highlight the importance of developing new therapeutic approaches and conducting in-depth studies on the factors associated with adherence to tobacco and cannabis cessation treatments via mobile phone applications.

Renal cell carcinoma (RCC) accounts for approximately 90-95% of all kidney cancers in adults, with the clear cell RCC (ccRCC) the most frequently identified subtype. RCC is known for its responsiveness to immunotherapy, making it an area of significant research interest. Immune checkpoint (IC) molecules, which regulate immune surveillance, are established therapeutic targets in RCC. The aim of this study was to analyze the influence of polymorphisms in genes HVEM and CD160 on susceptibility to ccRCC and patient overall survival (OS) with over a ten-year period of observation. We genotyped three HVEM single nucleotide polymorphisms (SNPs): rs1886730, rs2234167, and rs8725, and two CD160 SNPs: rs744877 and rs2231375, in 238 ccRCC patients and 521 controls. Our findings indicated that heterozygosity within rs2231375 and/or rs2234167 increases ccRCC risk. Furthermore, in women, heterozygosity within additional HVEM SNPs, rs8725 and rs1886730, is associated with an increased ccRCC risk. The presence of a minor allele for rs1886730, rs2234167, rs8725, and rs2231375 was also correlated with certain clinical features of the disease. Moreover, the rs1886730 SNP was found to be associated with patients' OS. In conclusion, our study highlights an association between HVEM and CD160 polymorphisms and the risk of developing ccRCC as well as patient’s OS.

This communication explores the transition from Cognitive Behavioural Therapy (CBT) to a more holistic model, named Complex Therapy, developed by Tullio Scrimali for explaining and treating mental disorders. The Author delves into the limitations of traditional CBT and introduces an innovative framework that integrates multiple therapeutic modalities. While CBT is based on the study and modification of behaviour and cognition, Complex Therapy includes, in its focus, the theory of human relationships, the attachment theory, neuroscience, applied neuroscience, complex systems theory and ecology.Complex Therapy addresses the multifaceted nature of mental health issues by combining evidence-based techniques with personalized care strategies. The goal is to enhance patient outcomes through a tailored, comprehensive treatment plan that adapts to the evolving needs of individuals facing mental health challenges.Two innovative and original items which Scrimali has developed, which are a device for Applied Neuroscience MindLAB Set and a new botanical drug, NegEnt, are presented and discussed.The topic also describes, an original and integrated protocol, named Negative Entropy, the author has developed for treating a challenging disorder, such as schizophrenia, he renamed Entropy of Mind.

Growth hormone (GH) deficiency affects up to 1 in 4,000 children and is usually treated with daily injections of GH whilst the child is still growing. With children typically diagnosed around 5 years old, this can mean over 10 years of therapy, which can place a considerable burden on the child and parent. Over three-quarters of children are estimated to be not fully compliant with therapy, which can compromise their chances of attaining their target height. In recent years, interactive mobile health (smart phone or tablet) interventions using game-like concepts, so called ‘gamification’, have increased in popularity and have demonstrated success in promoting positive self-management behaviour in children with chronic conditions, such as diabetes. The application of gamified interventions has the potential to support adherence to therapy and positive behaviour in children with GH deficiency in a number of ways: 1) By providing education in a format that the child understands and accepts (e.g. using behavioural constructs to facilitate explaining why adherence is important); 2) By providing a mechanism to reduce the anxiety and stress associated with administering the injection (e.g. diversion with a virtual pet); and 3) By providing feedback to encourage on-going engagement (e.g. rewards, progression through levels).

We aimed to explore symptoms severity and adherence to therapy for patients with myelofibrosis treated with ruxolitinib in Bulgaria. It is a prospective, non-interventional study performed at the Specialized hospital for active treatment of hematological diseases in Sofia during 2022 - 2023. Date of diagnosis, demographic characteristics, clinical indicators, ruxolitinib dose, and other data points were collected. Clinical indicators were assessed at baseline, in the middle and at the end of observation. Severity of symptoms was measured with MPN-SAF TSS and adherence to therapy with the Morisky 4 questionnaire 6 times during the observation. The mean age of diagnosis was 58.5 years, with the average duration of disease of 3 years. Pa-tients’ laboratory results were within physiological ranges, with spleen size experiencing a con-stant decrease. The average value for the severity of the symptoms per MPN-SAF TSS results decreased significantly, indicating better disease control. The average adherence to therapy did not change and remained high at around 9 points, except for one patient. In conclusion the treatment of myelofibrosis patients with ruxolitinib decreased symptoms se-verity and spleen size. Patients were adherent to the therapy over the observed period but as treatment duration increases the risk of adherence decreasing.

Objectives: Evaluate the performance of diagnostic measures (sensitivity and specificity) of the intrinsic capacity (IC) construct recommended by the WHO ICOPE guidelines by domain and by age group. Study design: This cross-sectional study included 164 community-dwelling elderly (95 women and 69 men). The participants completed the assessment of the 5 domains of IC (cognition, psychological, vitality, locomotion and sensory). In addition, they were assessed for activities of daily living (ADL), instrumental activities of daily living (IADL), frailty and urinary incontinence. Main outcomes measures: Descriptive statistics were used to summarize the intrinsic capacity and identify which domains were compromised. Comparisons between three or more samples were made by 1-way ANOVA with Bonferroni post-test and those with two samples by the t-test or Mann-Whitney test for quantitative variables. Chi-square test was used for qualitative variables. The sensitivity and specificity of each domain and each domain by age group were evaluated using the ROC curve. Results: Participants with a decline in IC were older, worse ADL, IADL and mental function, low gait speed, and higher depression scores. In addition, people with a decline in IC had frailty, urinary incontinence. Other issues related to the decline in CI were self-reported non-practice of physical activities and level of schooling.The evaluation of each domain did not prove to be a good screening tool (sensitivity or specificity < 80%, but both values > 50%). When the analyses were separated by domain and age group, good performance was found in the psychological (69-69 years and ≥80 years), vitality (≥80 years) and sensory (≥80 years) domains. Conclusions: The ICOPE screening tool performed well in terms of diagnostic measures when applied by domain and age group.

Background: Atopic dermatitis is a chronic condition that significantly affects the daily life of those who suffer from it, requiring complex and personalized management with active participation of the patient in the management of their disease. Objective: to describe the design and development process of a mobile application, using the Design Thinking method, for the follow-up of patients with atopic dermatitis. Methods: User-centered design and prototype creation method, differentiating the phases of the empathize, define, idea, prototype, and test. A purposive snowball sampling was used to recruit patients with atopic dermatitis, family members, and health professionals. Three two-hour workshops were held, attended by 25 people. Results: the parameters to be monitored will include objective data (physical, behavioral, treatments, environmental, integration of daily routines) and subjective data (user experience). On the other hand, it will figure out behavior patterns, set up rewards, foster a feeling of community, and use notifications and a chatbot. Conclusion: The active integration of all stakeholders at each stage of the design and development of the digital solution has improved its relevance and acceptance, resulting in a tool that is expected to significantly improve the management of atopic dermatitis.

This study aimed to investigate the efficacy of manual therapy and exercise versus synchronized telerehabilitation with self-manual therapy and exercise in treating Subacromial Pain Syndrome (SAPS). Sixty individuals diagnosed with SPS, aged 18-50 years, were randomly assigned to home exercise (HE), manual therapy (MT), and telerehabilitation (TR) groups. Treatment protocols were administered over 8 weeks and included specific exercises and therapy interventions. Out-come measures included Visual Pain Scale (VAS), shoulder range of motion (ROM) via gonio-metric measurements, Quick Disability Arm-Shoulder-Hand Problems Survey (Q-DASH), and patient satisfaction. Results revealed that both MT and TR groups exhibited reduced pain, in-creased ROM, lower Q-DASH scores, and higher patient satisfaction compared to the HE group. However, no significant differences were found between MT and TR groups in pain levels, ROM, Q-DASH scores, or patient satisfaction. The study concludes that both telerehabilitation and manual therapy effectively alleviate pain and are well-received by patients with SPS. Addition-ally, manual therapy demonstrates superiority in enhancing functional levels compared to exer-cise-based interventions. (Registration: NCT05200130)

Objective. To test the hypothesis that a session of unilateral tSMS over the dominant primary motor cortex (M1) in healthy subjects produces a transient decrease in manual dexterity. Methods. A triple-blinded randomized control trial was conducted in 40 healthy participants who were allocated to real- or sham-tSMS group. Each participant underwent one session of tSMS and were assessed before, immediately after, 15 minutes, and 40 minutes after stimulation. Outcome measures were Finger Tapping Test (FTT), 5-seconds FTT, nine Hole Peg Test, and the hand grip assessment. Results: Significant differences were found between groups 15 minutes after stimulation in favor of the tSMS group in the FTT (2.2 ± 0.99; CI= .18-4.22; d= .84p=.034), and 5-second FTT (4.2 ± 1.98; CI= .199-8.2, d= .68; p=.04). In the intragroup analysis, a significantly lower number of taps 15 minutes after stimulation was observed in sham group (3.3 ± 1.01; CI= .47-6.13; d= .42; p=.015), but not in the real stimulation group. Conclusion: A unilateral session of tSMS in the M1 of the dominant hemisphere of healthy individuals does not reduce manual dexterity or grip strength. This technique could have benefits on the motor performance of the arm contralateral to the stimulated motor cortex

Background: Intrauterine transfusion (IUT) of the donor and partial exchange (pET) of the recipient is a temporizing treatment for pregnancies with Twin Anemia Polycythemia Sequence (TAPS). We sought to give a detailed description of the procedural approach and outcomes for sequential donor IUT and recipient pET in TAPS. Methods: Retrospective study of spontaneous TAPS referred to the Johns Hopkins Center for Fetal Therapy treated with donor IUT followed by recipient pET utilizing a double-syringe set up. Procedure characteristics and outcomes as well as accuracy of existing transfusion formulas were analyzed and compared with the literature. Results: 5 of 78 patients with spontaneous TAPS underwent a total of 19 combined IUT/pET procedures (median first procedure to delivery interval 5.6 weeks [interquartile range IQR 1.9-6.0]). One pET was stopped for fetal decelerations. Patients delivered at 33.0 weeks [IQR 31.9-33.3] with two survivors and no neonatal transfusion requirements. IUT volumes were 48 ml [IQR 39-63 ml] and pET volumes 32 ml [IQR 20-50] utilizing aliquots of 5 – 20 mls for the latter (p=0.021). For IUTs, assumption of a fetal blood volume below 150 ml/kg underestimated required transfusion volume. For pETs, all formulas required adjustment of dilution volume based on bedside testing (p<0.05 for all). Conclusions: Donor transfusion followed by partial exchange in the recipient can prolong pregnancy in spontaneous TAPS and obviate the need for neonatal transfusion. A double-syringe setup facilitates efficient saline exchange. Because the accuracy of volume formulas is limited, bedside testing is recommended to achieve the target hemoglobin.

Off-grid electrification planning increasingly recognizes the importance of productive use of electricity (PUE) to promote community value creation and (financial) project sustainability. To ensure a sustainable and efficient integration in the community and energy system, PUE assets must carefully be evaluated to match both the community needs and the residential electricity demand patterns. We propose a novel methodology interlinking qualitative interviews, statistical analysis, and energy system modelling to optimize decision-making for PUE integration in off-grid energy systems in rural Madagascar by aligning relevant PUE effectively with anticipated residential electricity demand patterns based on socio-economic determinants of the community. We find that a possible contribution of the PUE to reducing the electricity costs depends signifi-cantly on three factors: 1. the residential electricity consumption patterns that are influenced by the socio-economic composition of the community, 2. the degree of flexibility of i) PUE assets and ii) operational preferences of the PUE user, and 3. the capacity of community members to finance and operate PUE assets. Our study demonstrates that significant cost reductions for PUE-integrated off-grid energy systems can be achieved by applying our proposed methodology. When matching PUE and residential consumption patterns, the integration of PUE assets in residential community energy system can reduce the financial risk of operators, provided the PUE enterprise operates reliably and sustainably. We highlight that the consideration of local value chains and co-creation approaches are essential to ensure the energy system is addressing the community’s needs, creates value for the community, enhances the project´s financial sustainability, and is achieving the overall objectives of decentralized energy system planning.

Objective: Subclinical left ventricular disfunction (LVD) is common in asymptomatic patients with type 2 diabetes (T2D). Many patients with diabetes have an impaired diastolic and systolic function. With preserved ejection fraction LV (EFLV), the latter is defined as reduced global longitudinal strain (GLS), detected using the speckle-tracking echocardiography. This study is aimed to define the long-term structural and functional disorders of the LV myocardium in patients with T2D without CVD. Methods: Of the 120 patients with and without T2D of both sexes aged from 45 to 75 years (57.11±7.9 years), included in the study in 2012-2013, only 57 responded to the follow-up study. The patients were divided into two groups: one with T2D (n=29), the other without it, control (n=28). All patients underwent transthoracic two-dimensional echocardiography with assessment of standard indicators of systolic and diastolic cardiac function, as well as GLS. In addition, all participants underwent laboratory diagnostics of carbohydrate metabolism disorders markers, NT-proBNP and CRP. The median follow-up duration was 7.2 [7.0-7.8] years. Results: During the follow-up, a statistically significant increase in the incidence of diastolic dysfunction (DD) in the type 2 diabetes group was found from 53% to 61% (p = 0.004); no significant dynamics were noted in the control group (p = 0.48). The presence of T2D significantly increases the risk of developing DD (p=0.04). The presence of T2D, increased fasting glucose levels, and an increased HOMA index were independent predictors of the development of DD. Impairment of LVEF was not observed in both groups. At the same time, the proportion of patients with reduced GLS (< -18%) increased in the T2D group (p = 0.036). A significant difference in the frequency of decreased GLS depending on T2D was demonstrated. The presence of obesity, an increase in the HOMA index and an increase in CRP levels are independent predictors of impaired GLS. Conclusions: T2D is an independent risk factor for the worsening of subclinical left ventricular dysfunction in asymptomatic patients with T2D without CVD over 7-year follow-up. Diastolic dysfunction is represented by delayed relaxation of the LV myocardium; with preserved LVEF, reduced 2D GLS identifies systolic dysfunction. The tight control of glycemia, lipidemia, blood pressure and body weight is associated with the absence of poor clinical outcomes.

Background: The laryngeal mask airway Vision Mask (LMA VM) is a supraglottic airway device (SAD) with vision guidance system. The ideal head and neck position for direct laryngoscopy is known, but the ideal position for placing a LMA is not. The objective of this study is to evaluate and compare the optimal position for placement of a video laryngeal mask airway. Methods: This was a prospective observational, transversal and analytical study of 72 consecutive patients. In the same patient, laryngeal vision was first assessed with the head and neck in the sniffing position and then with the head in the neutral position. Procedures were filmed and performed by the same investigator. Assessment of the laryngeal view was performed using two classifications: modified Cormack-Lehane classification and Brimacombe classification. Device placement was considered adequate when the Cormack-Lehane rating was scored from 1 to 2 and the Brimacombe rating was from 2 to 4. Results: 72 patients were included in this study. In the assessment of the glottis using the Cormack Lehane classification for fiberoptic view, laryngeal visibility was adequate in 64 (88.89%) patients in the neutral position and in 65 (90,28%) patients in the sniffing position (p>0,05). In the fiberoptic view of the glottis, assessed using the Brimacombe classification, laryngeal visibility was adequate in 68 (93%) patients in the neutral position and in 69 (95%) patients in the sniffing position, (p>0,05). There was no statistically significant difference in the rate of success between the sniffing position (70 patients, 97.22% success rate) and the neutral position (67 patients, 93.06% success rate) during the first insertion attempt. Two patients required a second attempt in the sniffing position, while five patients required a second attempt in the neutral position. Conclusion: An adequate sniffing position did not result in a better glottic view than neutral position, and the number and type of additional maneuvers were equal in both positions.

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease (CHD), hypertension, heart failure (HF), cerebrovascular disease, atrial fibrillation (AF), ventricular arrhythmias, and sudden cardiac death (SCD). In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen, and C-reactive protein and others, all of which increase the risk of CVD events. Mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokines dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left ventricular (LV) remodeling and diastolic dysfunction. Natural products of plants, provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discussed the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herbs and plants extracts for the prevention and treatment of CRFs are also reviewed.

Adeno-associated viruses (AAV) are widely used as viral vectors for gene delivery in mammalian cells. We focused on the efficacy of transduction of AAV 2/5, 2/6, 2/8 and 2/9 expressing GFP in 3T3-L1 murine preadipocyte cells by live imaging microscopy using IncuCyte S3 and flow cytom-etry. Three transduction modes were assessed: AAV transduction in 3T3-L1 preadipocyte cells with or without further differentiation into mature adipocyte-like cells and injection of AAVs in differ-entiated adipocyte-like cells. AAV2/6 demonstrated the highest transduction efficiency in 3T3-L1 preadipocytes, as it was 1.5–2-fold more effective than AAV2/5, and AAV2/8 in the range of viral concentrations from 2×104 to 1,6×105 VG/cell. AAV2/5 and AAV2/8 showed transduction effi-ciencies similar to each other. The expression of GFP under the CMV promoter remained stable for up to 20 days. The induction of 3T3-L1 differentiation in three days after AAV transduction did not alter the GFP expression level, and AAV2/6 showed the best transduction efficiency. AAV2/6 demonstrated the ability to transduce mature adipocytes. These results were confirmed by in vivo studies on C57BL6 mice AAV2/6 had the highest transducing activity on both inguinal and inter-scapular adipose tissue. Thus, AAV2/6 has demonstrated higher transduction efficacy compared to AAV2/5, AAV2/8 and AAV2/9 both in 3T3-L1 adipocytes and adipose tissue in vivo, which proves its usability along with AAV8 and AAV9 for gene delivery to adipocytes.

Background/Aim: Stool gluten immunogenic peptides (GIP) determination is now considered a valuable tool for detecting dietary lapses in treated celiac disease (CeD) patients. Our study aims to explore the diagnostic performance of a qualitative lateral flow immunoassay point-of-care test (LFIA/PoCT) compared with a qualitative enzyme-linked immunosorbent assay (ELISA) for detection of stool GIP. Methods: The study is a post hoc analysis of stool samples collected in the real-life conditions from a cohort of gluten-free diet-treated CeD patients. Stool GIP was measured in µg/g of stool using an ELISA kit (iVYLISA GIP S®, Biomedal SL). For the qualitative evaluation of stool GIP, a LFIA/PoCT test (GlutenDetect®; Biomedal S.L) was employed, which reported results as positive or negative. The LFIA/PoCT performance was evaluated against ELISA, considered as the gold standard. GIP concentrations

Protein degradation is a biological phenomena essential for cellular homeostasis and survivor. Selective protein degradation is performed by the ubiquitination system which selectively target proteins that need to be eliminated and lead them to proteasome degradation. In this review, we focus on the ubiquitin-conjugating enzyme E2 O (UBE2O) and highlight the role of UBE2O in many biological and physiological process. We further discuss the UBE2O implications in various human diseases, particularly in leukemias and solid cancers and suggest how UBE2O targeting could be novel strategy in the treatment of different human neoplasia.

Young people living with perinatal infections of Human Immunodeficiency Virus (YLPHIV) face a chronic disease, with treatment including adherence to life-long antiretroviral treatment (ART). The aim of this QES was to explore adherence to ART for YLPHIV as an assemblage within the framework of the BPS model with a new materialist perspective. We searched up to November 2021 and followed the ENTREQ and Cochrane guidelines for QES. All screening, data extraction and critical appraisal was done in duplicate. We analysed and interpreted the findings innovatively, by creating images of meaning, a storyboard, and storylines. We then reported the findings in a narrative first person story. We included 47 studies and identified 9 storylines. We found that treatment adherence has less to do with humans’ preferences, motivations, needs and dispositions, and more to do with how bodies, viruses, things, ideas, institutions, environments, social processes, and social structures assemble. This QES highlights that adherence to ART for YLPHIV is a multisensorial experience in a multi agentic world. Future research into rethinking the linear and casual inferences we are accustomed too in evidence-based health care is needed if we are to adopt multidisciplinary approaches to address pressing issues such as adherence to ART.

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.

Human induced climate change led to the recognition of Community-Based Adaptation (CBA) as one of the remedies in building adaptive capacity and resilience of communities. It recognizes the resources and the skills as well as the agency of communities in shaping the optimal strategy. CBA interventions are vital in addressing community needs and contextual specificities, enable participatory and inclusive engagement and thereby facilitate more profound adaptation impacts. Agent-based modelling (ABM) harbors the potential to be the ideal tool to support developing of tailored adaptation strategies while considering capacities, resources, skills, priorities, needs and the cultural context of local communities. ABM allows to capture the complex relationships among various components within community decision making on CBA actions, the CBA actions themselves and the environment. There exist plenty of tools, however they provide for varying degrees of freedom in agent definition, sensitivity analysis, scalability, experiment design and output analysis to name a few. A set of required key criteria for CBA modelling is developed and all available ABM modelling and simulation tools are assessed for their suitability for CBA. NetLogo emerges as the most fitting tool for incorporating and handling the special features of CBA. It is closely followed by GAMA and Envision. The article provides insights and guidance to researchers and practitioners in selecting ABM tools aligned with the specific requirements of their CBA simulations and projects.

Atopic dermatitis (AD) is a chronic inflammatory condition which significantly affects quality of life in both patients and their caregivers. Calcineurin inhibitors (CNI) are a class of immunosuppressive drugs predominantly inhibiting T cell mediated immune processes. CNI form complex by binding with immunophilins and in turn inhibit calcineurin and suppress downstream inflammatory pathway. Tacrolimus and pimecrolimus are topical CNI approved for the treatment of mild to severe AD in both children and adults. Application site reactions are frequently seen. They have been issued with black box warning towards increased risk of malignancies but supportive evidence is lacking. Cyclosporine, though highly effective, is used off-label for AD management. It is used for controlling acute flares of AD due to its very rapid onset of action. Nephrotoxicity and hypertension are its serious complications. CNI have not been reported with teratogenicity and may be used conditionally during pregnancy and lactation.

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-aminofluorene (2-AAF). HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, β-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.

Background: To compare photodynamic therapy 41 and the use of probiotics in reducing halitosis assessed through gas chromatography and microbiome analysis. Methods: Participants aged from 18 to 25 years, showing sulfide (SH2) ≥ 112 ppb on gas chromatography, were selected. They were divided into 4 treatment groups: Group 1 - Tongue Scraping; Group 2- Antimicrobial Photodynamic Therapy (aPDT); Group 3- Probiotics; Group 4- Antimicrobial Photodynamic Therapy (aPDT) and Probiotics. The halimetry process was performed before, immediately after the treatments, 7 days, 14 days and 30 days after the initial collection. The collections for later microbiological analysis were made along with the halimetry, for the microbiome analysis. Results: Treatment with aPDT or probiotics under these experimental conditions was not able to change the bacteria present in the biofilm of the tongue. Conclusions: More research is needed to know the behavior of the oral microbiome in the presence of halitosis and the effectiveness of new treatments.

Spinal cord injuries (SCI) can result in sensory and motor dysfunctions, which were long-considered permanent. Recent advancement in electrical neuromodulation has been proven to restore sensorimotor function in people with SCI. These stimulation protocols, however, were mostly invasive, expensive, and difficult to implement. In this study, transcutaneous electrical stimulation (tES) was used to restore over-ground walking of an individual with 21 years of chronic paralysis from a cervical SCI. After a total of 66 weeks of rehabilitation training with tES, which included standing, functional reaching, reclined sit-up, treadmill walking and active biking, significant improvement in lower-limb volitional movements and overall light touch sensation were shown by International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) score. By the end of the study, the participant could walk in a 4-meter walking test with the aid of a walking frame and ankle foot orthoses. The success in the sensorimotor recovery of our study participant sheds light on the future of non-invasive neuromodulation treatment for SCI paralysis.

Androgen deprivation therapy (ADT) for prostate cancer treatment is associated with adverse physiological changes, however exercise can improve outcomes. This systematic review and meta-analysis aimed to determine exercise intervention adherence, and its effects on physiological outcomes in men diagnosed with prostate cancer undergoing ADT. Uniquely, this review incorporates a meta-aggregation of qualitative data, providing perspectives from the men’s experiences. A systematic review and meta-analysis were completed following PRISMA Guidelines. Databases (CINAHL, Cochrane, PubMed) were searched for studies using “prostate cancer”, “exercise intervention”, and “androgen deprivation therapy”. Quantitative randomised controlled trials describing adherence to exercise interventions were selected, with qualitative articles selected based on descriptions of experiences around participation. Subgroup meta-analyses of adherence, exercise mode, and intervention duration were completed for quality of life, aerobic fitness, fatigue, and strength. Articles (n=64) articles were identified, with 29 (n=23 quantitative; n=6 qualitative) articles from 25 studies included. Exercise had no effects (p&lt;0.05) on quality of life and fatigue. Significant effects (all p&lt;0.05) were observed for aerobic fitness, and upper- and lower-body strength. Adherence to exercise-based interventions was 80.38%, with improvements observed in aerobic fitness and strength. Subgroup analysis revealed exercise adherence impacted fatigue and strength, with greater improvements observed in programs &gt;12-weeks.

This study aimed to evaluate the impact of Candida albicans on subgingival biofilm formation on dental implant surfaces. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to compare biofilm structure and microbial biomass in the presence and absence of the fungus after periods of 24, 48, and 72 h. Quantitative polymerase chain reaction (qPCR) was used to quantify the number of viable and total micro-organisms for each of the biofilm-forming strains. A general linear model was applied to compare CLSM and qPCR results between control and test conditions. The biofilm developed with C. albicans at 72 h had a higher bacterial biomass, with a significantly higher cell viability (p &lt; 0.05). After both 48 and 72 h of incubation, in the presence of C. albicans, there was a significant increase in counts of Fusobacterium nucleatum and Porphyromonas gingivalis and in the cell viability of Streptococcus oralis, Aggregatibacter actinomycetemcomitans, F. nucleatum, and P. gingivalis. Using a dynamic in vitro multispecies biofilm model, C. albicans exacerbated the development of the biofilm grown on dental implant surfaces, significantly increasing the number and cell viability of periodontal bacteria.

It is not new in medical history to propose a global concern to be classified as a disease. Defining a concern into disease allows to assign ethical responsibilities to develop powerful and effective interventions. It also allow to appropriate distribute the resources uniformly economically and morally. In 2003, World Health Organization report stated that 30-50 % of patients do not take their medications as prescribed associated with morbidity, mortality and health cost. It was considered a global concern, however, irrespective of decades of researches conducted on medication adherence, we are still unable to state that medication adherence issues are being resolved. In this review, we have described few apprehensions in current understandings of medication adherence that have limited its research. We have also proposed medication adherence as disorder and provided its’ definition and classification

With an aging population, the prevalence of geriatric diseases is increasing, especially among older individuals who live alone. This study investigates the potential of using TV viewing patterns to detect these diseases by analyzing variables such as daily average viewing time, peak viewing hours, and channel-switching behaviors. Significant correlations between TV viewing patterns and early indicators of geriatric diseases (depression, activities of daily living (ADL) performance, and cognitive function) were found. The correlations between the Korean form of the Geriatric Depression Scale (KGDS) and daily average viewing time and excessive channel switching were 0.320 and 0.308, respectively. The Korean version of the Modified Barthel Index (KMBI) showed correlations of -0.313 with daily average viewing time and -0.352 with excessive channel switching. Participants were divided into groups based on scores, and significant differences in peak viewing hours were observed among the different groups. The Korean version of the Mini-Mental State Examination (MMSE-K) groups showed significant differences at 3, 4, and 5 PM. The KGDS and KMBI groups showed significant differences at 8 PM and midnight and 1 AM and 2 AM, respectively. These findings suggest that TV viewing patterns can serve as effective early diagnostic indicators for geriatric diseases.

This paper investigates the efficacy of YOLOv8 variants for vehicle detection and license plate detection within smart parking applications, emphasizing performance under varying ambient lighting conditions. The proposed system is to seize full video frames, extracts regions of interest containing vehicles, and feeds them into separate, pre-trained YOLOv8 models – one dedicated to vehicle detection and another for license plate detection. Four YOLOv8 variants, nano, small, medium, and large, are evaluated. As a pre-processing step, the images are processed with the help of OpenCV and Pillow libraries to adjust the luminosity and increase the images’ DPI so that they would be easy to perceive by the Tesseract OCR engine. Sixteen potential combinations arise from pairing the four YOLOv8 models for vehicle and license plate detection tasks. To identify the most suitable combinations, we employ the Multi-Criteria Decision-Making method, specifically Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) analysis. This analysis considers 4 critical metrics: Precision, mean average precision at 95% Intersection of Union threshold, Recall and Total Inference Time. The objective is to achieve an optimal balance between high accuracy and real-time processing. Following the selection of optimal YOLOv8 combinations through TOPSIS analysis, we assess their performance under varying ambient light intensity (measured in lux). This evaluation aims to identify the most robust model combinations that ensure accurate vehicle and license plate recognition across the diverse lighting conditions encountered in real-world environment.

This article touched upon various issues regarding vulnerability, disparities amongst community settings, and the effect of air pollution on the populace (low-income communities). Furthermore, the paper emphasized environmental ethics approaches like anthropocentric, nature-centric, and deep-ecological approaches. More so, it addresses the importance of handling these disparities, particularly from the geopolitical dimension, and recommends cross-border cooperation and accountability in promoting environmental justice in India.

Biopolymer gels have gained tremendous potential for therapeutic applications due to their biocompatibility, biodegradability, and ability to adsorb and bind biological fluids, making them attractive for drug delivery and therapy. The versatility of biopolymer gels in theranostic backgrounds, with a focus on integrating imaging features and facilitating real-time monitoring of drug delivery. Different methods of delivery are explored imaging agents into biopolymer gels, including encapsulation, surface functionalization, nanoparticle encapsulation and layer-by-layer assembly techniques. Integration of Agents and Real-Time Monitoring Drug Delivery We summarize the synthesis methods, general properties, and mechanisms of biopolymer gels functionality, demonstrating their broad applications as multimodal systems for imaging-based therapeutics. These techniques not only enable multiple imaging but also provide signal enhancement and imaging a targeted facilitates, increasing the diagnostic accuracy and therapeutic efficacy. In addition, current techniques for incorporating imaging agents into biopolymer gels are discussed, and their role in precise drug delivery and monitoring.

This study investigates job satisfaction, burnout, and well-being among first-generation migrant physicians in anesthesia and intensive care medicine in Germany, comparing them to their native German counterparts. Utilizing a cross-sectional survey design, the study collected data from 513 physicians, 110 of whom identified as having a migration background. Job satisfaction was measured using the German version of the Warr-Cook-Wall (WCW) Job Satisfaction Scale, burnout was assessed with the Copenhagen Burnout Inventory (CBI), and well-being was evaluated using the WHO-5 Well-Being Index. The job satisfaction ratings revealed no significant differences between migrant and German physicians in most dimensions, including physical workload, freedom to choose work methods, satisfaction with colleagues, responsibility, income, skill utilization, and variety in work tasks. However, migrant physicians reported significantly higher satisfaction with recognition received for their work and lower dissatisfaction with working hours. Burnout assessments showed that migrant physicians experienced higher psychological strain, perceiving every work hour as more exhausting and having significantly less energy for family and friends. Notably, migrant physicians reported higher difficulty and frustration in working with patients. Well-being ratings indicated that migrant physicians felt less energetic and active but found their daily life more filled with interesting activities. The findings underscore the unique challenges faced by migrant physicians, particularly in terms of recognition and patient-related burnout. These results highlight the need for targeted interventions to support migrant physicians, including cultural competence training and flexible working hours to enhance their job satisfaction and overall well-being. Addressing these issues is crucial for maintaining the quality of patient care and the occupational health of migrant physicians in Germany.

Increasingly large numbers of people are using digital weight-loss services (DWLSs) to treat overweight or obesity. Although it is widely agreed that digital modalities improve access to care in general, obesity stakeholders remain concerned that many DWLSs are not comprehensive or sustainable enough to deliver meaningful health outcomes. This study adopted a mixed-methods approach to assess why and after how long patients tend to discontinue Austral-ia’s largest DWLS, a program that combines behavioural and pharmacological therapy under the guidance of a multidisciplinary care team. We found that in a cohort of patients who commenced the Eucalyptus DWLS between January and June 2022 (n=5604), mean program adherence was 171.2 (±158.2). Inadequate supply of a patient’s desired Glucose-like peptide-1 receptor agonist medication was the most common reason for discontinuation (43.7%), followed by program cost (26.2%), result dissatisfaction (9.9%), and service dissatisfaction (7.2%). Statistical tests revealed that ethnicity and age both had a significant effect on patient adherence. These findings suggest that DWLSs have the potential to improve access to comprehensive, continuous obesity care, but that care models need to improve upon the one observed in the Eucalyptus Australia DWLS to maximise program adherence.

Proteins play a pivotal role in supporting athletes by promoting muscle hypertrophy and minimizing protein catabolism during exercise. They stimulate muscle protein synthesis, aiding in the repair of exercise-induced muscle damage and serving as an energy source, particularly for post-exercise glycogen replenishment. In individuals with phenylketonuria (PKU), for whom protein intake is limited to essential phenylalanine (Phe), supplementation with Phe-free amino acids or glycomacropeptides is necessary. Tailored for macronutrient and micronutrient content, these protein substitutes fulfill most protein requirements, but lack Phe, unlike dietary sources of protein. Protein requirements for athletes with PKU exceed general recommendations due to limited availability in supplements and potential catabolism mitigation. Various factors influence tolerated dietary Phe in PKU, including protein substitute quantity, distribution, pharmacological treatment, age, growth rate, pregnancy, catabolic states, and physical activity. While general protein requirements for PKU surpass those of the general population, adherence to supplement regimens is crucial for athletes and patients with PKU. Strategically timed protein substitutes enhance muscle protein synthesis, body composition, and sports performance within safety limits. Individualized intake is essential for optimal outcomes, as proteins have a multifaceted role in optimizing athletic performance and addressing challenges in PKU.

The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains how novel cytokines and receptors can enhance CAR-NK cell efficacy, specificity, and functionality. The review underscores the advantages of CAR-NK cells, including reduced toxicity, lower cost, and broader accessibility compared to CAR-T cells, along with their potential in treating both blood cancers and solid tumors.

The extent of access to energy of displaced populations in settlements and camps in Africa is largely 14 unknown. A multitude of contextual factors, such as the location and the characteristics of housing, 15 the legal status, the socio-cultural background, and the availability of humanitarian and public ser- 16 vices impact the living conditions and the needed energy services. Limitations in accessing energy 17 services have direct, multilayered, and far-reaching implications, including impacts on health, nu- 18 trition, education, protection, and livelihood. The objective of this article is to contribute to a more 19 comprehensive overview of the current state of energy access in displacement contexts on the Afri- 20 can continent by identifying and utilizing existing data. After a screening of the vast and various 21 available information, setting up of a database, consolidating the gathered data as well as assessing 22 the quality through a quality assessment method, the currently available information is visualized 23 and discussed. Considerable differences in the access to electricity for displaced persons across the 24 countries are found. For both electricity and clean cooking, the availability for displaced persons 25 ranges from nearly no access at all up to an access rate of 100%. More strikingly, the results also 26 show that besides South Africa and countries in the Maghreb region, the access to both clean cook- 27 ing and electricity for displaced persons is very low. At the same time, the fragmented data availa- 28 bility, the poor data quality, and the questionable expediency of available data allows neither solid 29 theoretical conclusions nor planning of effective practical implementation measures. Novel inter- 30 disciplinary research, conceptual frameworks and indicators are needed for the purpose of compa- 31 rability and consistency. Future research has the potential to more comprehensively capture the 32 current state of access to energy in displacements contexts and in a next step to examine how energy 33 is interwoven in the lives of displaced people to derive a set of more detailed context-sensitive en- 34 ergy indicators. It is essential that the concerned persons, the displaced persons themselves are in- 35 cluded in the research in a meaningful way.

Art therapy fosters emotional healing and growth. This process can offer healthcare professionals (HCPs) novel insights into patients’ medication experiences. We developed a Metaverse Art Gal-lery of Image Chronicles (MAGIC), which depicted patients’ medication experiences symbolically as hero-villain portrayals. This gallery aimed to enhance healthcare students’ learning through re-latable insights into patients’ medication therapies. A character sheet was used to craft patients’ personifications of their medication experiences. ChatGPT, NightCafe, Canva, HeyGen and Cam-tasia were used to generate hero-villain portraits based on the character traits and mounted in MAGIC, which consisted of three virtual realms, each with a unique theme. Alpha-testing among sixteen Generation Z healthcare learners indicated that the content in MAGIC enabled them to understand the concepts of medication adherence (93.7%), art therapy (87.5%) and how patients related to their medications (81.3%). Perceived playfulness (rs=0.925, p

Uterine leiomyosarcoma (LMS) is a rare and aggressive form of uterine cancer, with a poor prognosis and high number of uterine cancer-related deaths. Chimeric Antigen Receptor (CAR) T-cell therapy is an immunotherapy approach to antigen specific of cancer cell, thereby enhancing the immune system's ability to target and destroy cancer cells. This study aims to investigate the potential of targeting differentially expressed genes (DEGs) as a novel therapeutic strategy using CAR T-cell technology in LMS. Genome datasets were obtained from NCBI-GEO database, Of the five datasets, genes that experienced significant overexpression in at least three datasets were categorized as DEGs, and DEGs were evaluated for protein localization, Gene Ontology, bioactivity, interaction, and overexpression. The results identified 25 DEGs, with ten of them expressed on the plasma membrane; four of them—HMMR, KIF20A, PRC1, and ZWINT—were part of the main protein network derived from the 25 DEGs. The dominant bioactivity of these PMGs involves influencing the cell cycle, particularly processes related to chromosome segregation. In conclusion, HMMR, KIF20A, PRC1, and ZWINT are high-potential DEGs as candidates for tumor-associated antigen CAR T-cell therapy. Further research, both in vitro and in vivo, is needed to enhance the validity of these findings.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm constituting approximately 15% of newly diagnosed leukemia in adult patients. Development of tyrosine kinase inhibitors (TKIs) have dramatically improved outcomes in patients with chronic CML in chronic phase. However, adverse drug events (ADEs) associated with TKI therapy have influenced drug adherence, resulting in adverse clinical outcomes and a decline in the quality of life (QoL). In this study, we carried out a unique questionnaire survey to evaluate ADEs, which comprised 14 adverse events. We compared drug adherence rates between patients using imatinib and those who switched from imatinib to nilotinib, a second-generation TKI. Following the switch, the total number of ADEs decreased considerably in most cases. Simultaneously, better QoL was observed in the nilotinib group than in the imatinib group. Drug adherence was measured using Morisky’s 9-item Medication Adherence Scale (MMAS). MMAS increased significantly after switching to nilotinib in all cases. Drug adherence is a critical factor for achieving molecular response in patients with CML. In fact, our results showed a strong inverse correlation between clinical outcome [international scale (IS)] and adherence (MMAS), with a stronger tendency in the nilotinib group than in the imatinib group. In conclusion, low occurrence of ADEs induced a high level of QoL and a good clinical response with second-generation TKI nilotinib treatment.

Our hypothesis that controlled ozone applications interfere into the redox balance of the biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl4 intoxication), has been verified over the last 2 decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes, diabetes-2 and in prevention of intoxications. Low-dose ozone acts as a redox bioregulator: The restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase of the antioxidant repair markers, here mainly shown as glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, relevant data are displayed, evaluated and comprehensively discussed: The repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone treated groups and depending on the indication; the stress markers are simultaneously reduced, the redox system regains its balance.

Renal replacement therapy (RRT), widely used in the treatment of renal injury in the course of sepsis, aims to eliminate the toxins and proinflammatory cytokines, involved in the pathomechanism underlying septic shock. Dialysis filters characterised by a high adsorption potential for cytokines in RRT when septic renal injury is the case. It is of key importance in the antibiotics treatment of sepsis to achieve desired values of PK/PD indices. Continuous renal replacement therapy (CRRT) may affect antimicrobial clearance, increasing their elimination in some cases. The aim of this study was to determine the degree of adsorption for linezolid, on three different types of filters used in CRRT. In our in vitro study a continuous veno-venous hemofiltration (CVVH) was conducted using 3 types of filters: polysulfone (PS), polyethyleneimine-treated polyacrylonitrile (PAN PEI) and non-PEI-treated polyacrylonitrile (PAN) filters. Each type of filter was used in 3 CVVH cycles, involving the use of 600 mg of linezolid dissolved in 700 ml of bovine blood or in 700 ml of 0.9% NaCl. In each case the total volume of the obtained solution was 1000 ml. Blood samples, at particular time points, were collected in order to measure drug concentration. The differences in mean drug/NaCl adsorption and drug/ blood adsorption were determined using one-way ANOVA with multiple comparisons by Tukey post-hoc test. A p-value of < 0.05 was considered to be significant. A significant adsorption of linezolid was found for PAN PEI filter, both in samples obtained from bovine blood and 0.9% NaCl solutions, at the endpoint. No significant adsorption was demonstrated on PAN or PS filters. There is a need for in vivo research to confirm the effect of filter type on linezolid concentration in patients undergoing CRRT.

This study investigates the effects of home-based Kakao health care breathing exercises and stretching on respiratory function and fatigue in COVID-19 cured patients. A total of 35 participants performed four movements of home-based breathing exercise and five respiratory muscle stretching exercises four times a week for four weeks. Respiratory function was measured using FVC, FEV1, FEV1/FVC, and PEF. Fatigue was assessed using the Fatigue Severity Scale (FSS). Data analysis was performed using Independent Samples and Paired Samples T-tests in SPSS 24, with a significance level set at p &lt; 0.05. After four weeks of Home based Kakao health care Breathing Exercise, there were significant increases in respiratory FVC, FEV1, FEV1/FVC, and PEF function values observed in the training group (T.G.) after the exercise intervention (p &lt; 0.05). Such an increase was observed when comparing these values with the pre-exercise measurements. In contrast, there was no statistically significant difference in respiratory function outcomes before and after exercise in the control group (C.G.) (p &gt; 0.05). The FSS scores were statistically significant within the training group (T.G.). (p &gt;0.05). The 4-week Kakao health care Breathing Exercise was found to be capable of improving some respiratory functions in COVID-19-recovered patients, but it showed no significant improvement in fatigue levels.

The realization of a perfect absorber A = 1 with transmittance and reflectance T=R=0 by a thin metasurface is one of the hot topics in recent nanophotonics prompted by energy harvesting and sensor applications (A + R + T =1 is the energy conservation). Here we tested optical properties of over 400 structures of metal-insulator-metal (MIM) metasurfaces for a range of variation in thickness of insulator, the diameter of a disc and intra-disc distance experimentally and numerically. Conditions of a near-perfect absorption A > 95% with simultaneously occurring anti-reflection property (R < 5%) were experimentally determined. Differences between the bulk vs. nano-thin film properties at mid-IR of the used materials can be of interest for plasmonic multi-metal alloys and high entropy metals.

Background/Objectives: interpretation of evidence on de-escalation of triple therapy with with-drawal of inhaled corticosteroids (ICS) to dual bronchodilator therapy with a long-acting musca-rinic antagonist (LAMA) and a long-acting beta-agonist (LABA) in patients with chronic obstruc-tive pulmonary disease (COPD) is conflicting. We evaluated the efficacy and safety of ICS discon-tinuation from LABA-LAMA-ICS triple therapy compared to its continuation. Methods: we searched PubMed, Embase, Scopus, Web Of Science, clinicaltrial.gov and CENTRAL for RCTs and observational studies from inception to March 22, 2024, investigating the effect of triple therapy de-escalation with withdrawal of ICS to dual therapy on the risk of COPD exacerbation, pneumonia and lung function. This study was registered with PROSPERO, CRD42024527942. Results: 3335 studies were screened; three RCTs and three real-world non-interventional studies were ultimately identified as eligible. Analysis of the time to the first moderate or severe exacerbation showed a pooled HR of 0.96 (95% CI, 0.80 to 1.15; I²=77%) for ICS withdrawal compared with triple therapy continuation. Analysis according eosinophil levels showed that COPD subjects with ≥300 eosino-phils/µL had a significant increase in the incidence of moderate or severe exacerbations when de-escalated from ICS/LABA/LAMA to LABA/LAMA (pooled HR: 1.35, 95% CI 1.00-1.82; I2: 56%). The ICS withdrawal in favour of LABA/LAMA did not significantly affect the risk of mortality and pneumonia. Conclusions: the main findings of this meta-analysis are consistent with current recommendations and suggest that the use of eosinophil counts may be of help in guiding maintenance therapy. However, methodological heterogeneity between the included studies is evident.

Obstructive sleep apnea (OSA) often goes unrecognized despite common symptoms such as excessive daytime sleepiness, fatigue, and impaired quality of life (QoL). CPAP is the gold standard treatment for OSA, but optimal daily usage and time needed for observable effects remain unclear. This study aimed to investigate the short-term effects of CPAP on daytime sleepiness and QoL in patients with severe OSA. Medical records were collected from 87 patients with severe OSA who initiated CPAP therapy. Also, validated questionnaires were used before and after one month of CPAP to analyze QoL - the Calgary Sleep Apnea Quality of Life Index (SAQLI), the Cues to CPAP Use Questionnaire (CCUQ), and daytime sleepiness - the Epworth Sleepiness Scale (ESS). Multiple regression analysis was conducted to identify predictors of CPAP usage. Of the total participants aged 55.6±12.5, 77% were males, and 62% were CPAP adherent. Reductions in daytime sleepiness (ESS) were noted, as well as improvements in both overall QoL (SAQLI) and specifically in the domains of daily functioning, social interactions, emotional well-being, and symptom perception. Important cues for CPAP usage recognized by patients were physicians’ instructions and physicians’ worry regarding patients' condition. Furthermore, multiple regression revealed higher SAQLI scores and lower ESS scores as positive predictors of CPAP usage, along with lower AHI after one month of CPAP being associated with sufficient adherence.

Abstract: Spinal disorders are some of the most prevalent health concerns, especially among stu-dents. Based on student demographics, this cross-sectional study evaluated the correlation be-tween functional tests (FT) and spinal range of motion (ROM). This study included 206 students from Vasile Alecsandri University of Bacău. Participants' assessments were conducted using the following tests: (i) Ott, (ii) Schober, (iii) Stibor, (iv) finger-to-floor distance, (v) lateral flexion of the cervical and lumbar spine, and (vi) flexion of the cervical spine. Correlation analyses were evaluated using Spearman correlation coefficient analysis. The results indicated a very strong re-lationship between lateral flexion of the lumbar spine on the left (LFLSL) and right (LFSR) for all departments (r = 0.85 to 0.97, p < 0.05). There was a stronger relationship between FT results and spinal ROM of physical education department students compared to students from other de-partments (n = 17, r = -0.38 to 0.93, p < 0.05). There was no statistically significant correlation be-tween FT and spinal ROM based on age (p > 0.05). The study results provide evidence of the pri-mary risk factors that predispose students to postural deviations. Practitioners and physiothera-pists can utilize these values as a reference for potential therapeutic interventions.

According to current forecasts, global heating is likely to exceed 2,8°C by the end of the century. This makes substantial adaptation measures necessary to secure a broad basis for livelihoods provision and the conservation of biodiversity. While the implementation of top-down and technocratic adaptation efforts is the majority, related adaptation shortcomings of socio-economic and ecological nature are becoming more and more apparent. Community-based adaptation (CBA) with its participatory, inclusive and needs-based bottom-up approach offers a promising and powerful alternative. This article uses a semi-systematic literature review approach to screen the current literature and identify core issues of CBA. Linking communality, locality, multidimensionality, power imbalances, transformative potential, localisation, the triad of adaptation metrics and adaptation with nature to corresponding potential actions for practical implementations provides a more holistic conceptualisation and broadens the horizons for further learnings, research and improved application.

In recent years, bioengineered and biotechnological products have gained tremendous attention to identify unique biologic features associated with oncology. To overwhelm the complexity of tumor personalized medicines (PM) or vaccines could be a promising way-out to be considered. Cancer is a heterogeneous disease. This characteristic variability of cancer provides itself to the emergent era of PM i.e., precision oncology. The prime objective of PM is merely to deliver the right treatment to the right patient at the right time. For instance, imatinib was effectively targeted chronic myeloid leukemia. To date, attainment in using PM approaches to cancer treatment have been mixed. The next-generation sequencing (NGS), and the use of several biomarkers (e.g., HER2, BRAF, ALK, etc.), to drive precise cancer treatment through a timely and cost-effective manner. In current review, author summarizes the advancement in the field of PM such as CRISPR-Cas9, NGS, pharmacogenomics, and the benefits of machine learning techniques. The precise communication between healthcare professionals, regulatory bodies, and patients is essential to translate advances in PM into immense benefits for patients with cancer globally.

The search of DNA polymorphisms useful for the genetic improvement of dairy farm animals lasts more than 40 years with relevant findings in cattle for milk traits, where the best combination of alleles for dairy processing have been found in casein genes and in the DGAT1. Nowadays, similar results are not reached yet in river buffaloes despite advanced genomic technologies and accurate phenotype records are available. The aim of the present study was to investigate and validate in a larger buffalo population the effect on six milk traits of four single nucleotide polymorphisms (SNP) in the CSN1S1, CSN3, SCD and LPL genes, previously reported to be associated with or affect dairy traits in smaller populations often belonging to one farm. A total of 800 buffaloes were genotyped. Daily milk yield (dMY, kg), protein yield (dPY, kg) and fat yields (dFY, kg), fat and protein contents (dFP, % and dPP, %), somatic cell count (SCC, 103cell/ml) and urea (mg/dl) were individually recorded in each month for the whole lactation from 2010 to 2021. A total of 15,742 individual milk test day records (2,496 lactations) were available on 680 buffalo cows with 3.6±1.7 parity (from 1 to 13) and 6.1±1.2 test day records per lactation on average. Three out four SNP in CSN1S1, CSN3 and LPL were associated with at least one of analyzed traits. In particular, the CSN1S1 (AJ005430:c.578C&gt;T) gave favorable associations with all yield traits (dMY, p=0.022; dPY, p=0.014 ; dFY, p=0.029) and SCS (p=0.032), whereas the CSN3 (HQ677596: c.536C&gt;T) positively associated with SCS (p=0.005) and milk urea (p=0.04). Favorable effect on dMY (p=0.028), dFP (p=0.027) and dPP (p=0.050) were observed for the LPL. Conversely, SCD did not show any association with milk traits. This is the first example of confirmation study carried out in the Mediterranean river buffalo for genes of economic interest in dairy field and it represents a very important indication for the preselection of young bulls destined to breeding programs in the view of a more sustainable dairy production.

In the frame of the I-MOVE-COVID-19 project, a cohort of 2050 patients admitted in two Spanish reference hospitals between March 2020 and December 2021 was selected, and a range of clinical factors data were collected at admission to assess their impact on the risk COVID-19 severity outcomes through a multivariate adjusted analysis and nomograms. The need for ventilation and ICU admission were found directly associated with a higher mortality risk (OR 6.9 and 3.2, respectively). The clinical predictors of mortality were need for ventilation and ICU, advanced age, neuromuscular disorders, thrombocytopenia, hypoalbuminaemia, dementia, cancer, elevated CPK and neutrophilia (OR between 1.8 and 3.5), whilst the presence of vomiting, sore throat and cough diminished risk of death (OR 0.5, 0.2 and 0.1 respectively). Admission to ICU was predicted by the need for ventilation, abdominal pain and elevated LDH (OR 371.0, 3.6 and 2.2, respectively) as risk factors; otherwise, it was prevented by advanced age (OR 0.5). In turn, the need for ventilation was predicted by low oxygen saturation, elevated LDH and CPK, diabetes, neutrophilia, obesity and elevated GGT (OR between 1.7 and 5.2), whilst prevented by hypertension (OR 0.5). These findings could enhance patient management and strategic interventions to combat COVID-19.

The Mediterranean diet represents one of the most studied dietary patterns, however, there is no single tool for measuring the grade of adherence and no single criteria to adapting these indices to pregnant women. We characterized the adherence to the Mediterranean diet (MDA) of pregnant women participating in the NELA cohort and identified the sociodemographic determinants and lifestyle habits associated with a higher risk of a low MDA. Maternal diet during gestation was assessed by a validated Food Frequency Questionnaire (FFQ) (n=665). We estimated Relative Mediterranean Diet score (rMED), Alternative Mediterranean Diet score (aMED) and Alternate Healthy Index-2010 (AHEI-2010). Multivariate regression models were performed to identify the sociodemographic and lifestyle factors associated to each index. Mothers with lower age and more previous deliveries had a greater probability of low MDA (P &lt;0.05). Only, for aMED index, mothers with university education and / or who practiced 2 or more hours per week sport activities had a lower probability of a low MDA (P &lt;0.01). These results may be useful in order to design intervention strategies and dietary recommendation for pregnant women.

Background: Low back pain (LBP) is a major cause of disability globally, and the diagnosis of LBP is challenging for clinicians. Objective: This study aimed to assess the accuracy level of arti-ficial intelligence as a Clinical Decision Support System (CDSS) called Therapa compared to MRI in predicting lumbar disc herniated patients. Methods: One hundred low back pain patients aged ≥18 years old were included in the study. The study was conducted in 3 stages, at first, a case se-ries was conducted by matching MRI and Therapha diagnosis for 10 patients. Subsequently, Delphi methodology was employed to establish a clinical consensus. Lastly, to determine the ac-curacy of the newly developed software, a cross-sectional study was undertaken, involving 100 patients. Results: The software showed a significant diagnostic accuracy with the area under the curve in the ROC analysis determined as 0.84 with a sensitivity of 88% and a specificity of 80%. Conclusion: The study’s findings revealed that CDSS using Therapha has a reasonable level of ef-ficacy, and this can be utilized clinically to acquire faster and more accurate screening of patients with lumbar disc herniation.

Accurate determination of the concentration of alcohols and their metabolites is important in forensics and in several life science areas. A new method has been developed to quantify alcohols and their oxidative products using a headspace gas chromatography- mass spectrometer and isotope-labelled internal standards. This work demonstrates the application of this method, specifically in quantifying the concentration of oxidative products of alcohol and other minor alcohols found in hand sanitizers, which have become an essential household item since the COVID-19 pandemic. Apart from the major component, the minor alcohols found in hand sanitizers include methanol, isopropanol, and n-propanol. In ethanol-based hand sanitizers, a significant amount of acetaldehyde was observed as an oxidation product, while in isopropanol-based hand sanitizers, acetone was observed. The concentration of acetaldehyde in ethanol-based hand sanitizers significantly increased with storage time and temperature, whereas no such increase of acetone concentration was observed in isopropanol-based hand sanitizers with storage time and temperature.

Personal protective equipment (P PE) rules must be respected and followed to the letter of healthcare professionals in Cameroon to avoid the transmission of infectious diseases. This research proposes solutions to the problems of non-adherence and non-compliance among healthcare workers in Cameroon towards PPE rules. Inadequate access to suitable PPE, discomfort when wearing PPE during poor quality, and a lack of training on correct PPE use are just a few of these obstacles amongst HCWs in Cameroon. Hospitals and healthcare facilities should prioritize offering thorough instruction on PPE use and pinpoint the need to adhere consistently to PPE rules to remove these obstacles. They should also ensure that all healthcare personnel have access to and a sufficient supply of the proper PPE. Through the organization of impromptu visits by surveillance teams to identify areas of support and training, there is a need for assistance from government bodies and public health groups in creating awareness of the security value of PPE use among healthcare professionals. There is a lack of PPE in health care settings in rural areas in Cameroon, thus a need for an adequate supply. Then can we put appropriate PPE policies and practices for HCWs in Cameroon, as they will keep to it.Healthcare professionals in Cameroon must comprehend that following PPE standards protects not just their selves from diseases but also their patients, coworkers, and communities. We are accountable for ensuring everyone's safety and well-being, and adhering to PPE regulations is an essential first step.

Senna rugosa is a species found in the Cerrado and used in folk medicine as a vermifuge and in the treatment of poisonous snakebites accidents. In this work, we identified the main secondary metabolites present in ethanolic extracts of the leaves (ELSR) and roots (ERSR) of S. rugosa and evaluated the potential cytoprotective effect against cellular macromolecular damage, as well as the cytotoxic properties of the extracts on the K562 and Jurkat leukemic cell lines. The identification of metabolites was done by liquid chromatography coupled with mass spectrometry. The antioxidant activities were investigated by direct ABTS•+ and DPPH• radical scavenging methods, protection against oxidative damage in proteins and DNA. The cytotoxic properties were investigated against healthy cells, isolated from human peripheral blood (PBMC) and leukemic cell lines. The leaf extract contains catechin, rutin, epigallocatechin derivatives, kaempferol glycosides, luteolin, and dimeric and trimeric procyanidins, while the root extract profile shows obtusichromoneside derivatives, 2-methoxystypandrone, stilbene derivatives, naphthopyranones, and flavanone derivatives. The extracts showed antioxidant activity, with IC50 of 4.86 ± 0.51 µg/mL and 8.33 ± 0.90 µg/mL in the ABTS assay for ELSR and ERSR, respectively. And in the DPPH• assay, the IC50 was 19.98 ± 1.96 µg/mL for ELSR and 13.37 ± 1.05 µg/mL for ERSR. The extracts protected macromolecules against oxidative damage at concentrations of 5 µg/mL. The cytotoxicity test against leukemic strains was observed after 24 and 48 hours of treatment. After 48 h, results against the K562 cell line demonstrate IC50 of 242.54 ± 2.38 µg/mL and 223.00 ± 2.34 µg/mL for ELSR and ERSR , respectively. While against the Jurkat cell line, these extracts showed IC50 of 171.45 ± 2.25 µg/mL and 189.30 ± 2.27 µg/mL, respectively Results on PBMC viability, demonstrate that the extracts showed selectivity for the leukemic cell lines. Together, our results reveal that the leaves and roots of S. rugosa have completely distinct and complex chemical compositions. This study expands the repertoire of identified chemical compounds and underscores their significant pharmacological potential in conditions related to oxidative stress and leukemia.

Osteoarthritis and chronic pancreatitis comorbidity are insufficiently studied, and the reciprocal impact of these conditions remains poorly understood. This study aimed to investigate potential predictors for the development of osteoarthritis and chronic pancreatitis comorbidity, as well as complications associated with this comorbidity. A cohort of 150 patients was categorized into three groups: a control group (n=30), patients with osteoarthritis (n=68), and patients with comorbid osteoarthritis and chronic pancreatitis (n=52). Potential predictors for comorbidity development and associated complications were explored. The study revealed that concurrent osteoarthritis and chronic pancreatitis exacerbate each other's progression and contribute to malnutrition. Body Mass Index (BMI) emerged as a potential predictor for chronic pancreatitis development in osteoarthritis patients. In osteoarthritis patients, fecal elastase-1 levels were identified as potential predictors for exocrine pancreatic insufficiency. Factors such as WOMAC total score, fecal elastase-1, C-reactive protein (CRP), ferritin, retinol, tocopherol, 25-hydroxy vitamin D3, and BMI were found to influence comorbidity development between osteoarthritis and chronic pancreatitis. Additionally, Gastrointestinal Symptom Rating Scale-Diarrhea Syndrome (GSRS-DS), Gastrointestinal Symptom Rating Scale-Constipation syndrome (GSRS-CS), Qualitative Assessment of the Symptoms and Impact of Pancreatic Exocrine Insufficiency domain A (PEI-Q-A), retinol, tocopherol, and iron were identified as potential predictors for exocrine pancreatic insufficiency in osteoarthritis patients. In conclusion, the comorbidity of osteoarthritis and chronic pancreatitis exacerbates disease progression and complications, necessitating further investigation.

In this review we aim to address the current status of phage therapy in the management of multidrug-resistant infections, from compassionate use cases to ongoing clinical trials, as well as the challenges this approach presents in the particular context of CF patients.

Antibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents. In this review, we summarize the latest advancements in ABCs. More importantly, we provide an overview and outlook on novel antibacterial agent-loaded bone cements, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides, etc. Offering novel perspectives for designing ABCs and treating bone infections.

Celiac disease (CD) is a genetically conditioned autoimmune process that appears in susceptible people. It can affect people of any age, and slightly predominates in females. It has a fairly homogenous global distribution, with an average prevalence of 1-2%, the frequency having increased in recent decades. The only effective treatment is a strict and permanent gluten-free diet (GFD), although the level of compliance with it is poor, at about 50% of cases. To monitor the effectiveness of the GFD, several procedures involving various approaches are employed: a) periodic interviews by nutritionists; b) clinical follow-up; c) serological controls of specific antibodies; d) endoscopies with collection of duodenal biopsies; e) structured questionnaires; f) determination of gluten peptides derived from gluten in feces and/or urine. All of these procedures are useful when applied, alone or in combination, depending on the cases. Some patients will only need to consult to their doctors, while others will require a multidisciplinary approach to assess their compliance with the GFD. In children, normalization of duodenal mucosa was achieved in 95% of cases within 2 years, while it is more delayed in adults, whose mucosa take longer to heal completely.

In the process of sewage coagulation treatment, quartz sand is often used as a heavy medium to accelerate the settling rate of flocs, but it will adversely affect the removal efficiency of pollutants. The factors that affect the coagulation effect and can be controlled manually include the quartz sand dosage, coagulant dosage, sewage pH, stirring time, settling time, etc, their reasonable setting is critical to. This paper was to study the optimal conditions of quartz sand enhanced coagulation(QSEC), first, single-factor tests were conducted to preliminarily explore the optimal range of influencing factors, and then response surface methodology（RSM）tests were performed to accurately determine the optimums of significant factors. The results showed that the addition of quartz sand can’t improve the water quality of coagulation treatment, but it can significantly accelerate the coagulation settlement process, the quartz sand dosage, the coagulant dosage and sewage pH all impacted significantly on its coagulation effect, and existed inflection points. A model that could guide QSEC was obtained by RSM tests. The model optimization and experimental validation showed that the optimal QSEC conditions for treating domestic sewage were as follows: the polyaluminum chloride(PAC) dosage, cationic polyacrylamide(CPAM) dosage, the sewage pH, quartz sand dosage, stirring time and settling time were 0.97 g·L-1, 2.25 mg·L-1, 7.22, 2 g·L-1, 5 minutes and 30 minutes, respectively, and the turbidity of treated sewage was reduced to 1.15 NTU.

The pervasive use of plastic for milk packaging has raised significant health concerns, despite its advantages in terms of cost-effectiveness, convenience, and durability. The potential correlation between cancer and plastic packaging is one of these concerns. This mini-review examines the health implications of plastic materials used in milk packaging, with a particular emphasis on their carcinogenic hazards. This work endeavors to summarize the current state of knowledge regarding the influence of plastic components on human health and underscore the importance of ongoing research in this field by utilizing insights from a comprehensive review article. Harmful chemicals have been observed to leach into milk from plastics used in milk packaging, including high-density polyethylene (HDPE), low-density polyethylene (LDPE), and polyethylene terephthalate (PET), particularly under conditions of protracted storage and heat. Bisphenol A (BPA), phthalates, and styrene are among the most prevalent leachates. These chemicals have been associated with a variety of health issues, such as an elevated risk of cancer, and are recognized for their endocrine-disrupting properties. BPA and phthalates, in particular, have the potential to disrupt hormone function, which may result in breast cancer, prostate cancer, and other hormone-related malignancies.This review emphasizes the significance of comprehending the precise components of plastics utilized in milk packaging and their potential health consequences. It advocates for more rigorous research to completely elucidate the long-term health impacts of these materials by emphasizing the current state of knowledge and regulatory initiatives. Additionally, it underscores the necessity of innovative packaging technologies to guarantee consumer protection and mitigate the risk of exposure to carcinogenic substances.

Work disparities experienced by nurses in long-term care (LTC) can impact the retention, well-being, and health of this workforce. Despite the significant impact disparities experienced by nurses have on the workforce and LTC sector, a review of the available literature on work disparities has not been conducted on work disparities experienced by nurses in LTC. Consequently, this scoping review aimed to explore the nature and extent of research on meso-level work disparities experienced by nurses in LTC and how such disparities are linked with nurse health and well-being. Five databases were searched: MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), and CINAHL (EBSCO host). Of the 5,652 articles retrieved, 16 studies published between 1997 and 2024 met the inclusion criteria. The average number of work disparities within each study was 3.06 (minimum = 1, maximum = 6, SD = 1.62). Types of work disparities across the 16 studies were work opportunities (n = 19), work treatment (n = 18), job security (n = 8), and work compensation (n = 8). Only four articles investigated the association of a work disparity with a variable of health and well-being. Future research on how macro-level disparities intersect with meso-level work disparities may inform a contextual understanding of how disparities transpire in the work of nurses in LTC. Studies are required to address the gaps in knowledge regarding how work disparities negatively influence the health of nurses to inform better retention, well-being, and health of nurses in LTC.

The process of developing therapies to treat rare diseases is fraught with financial, regulatory, and logistical challenges that have limited our ability to build effective treatments. Recently, a novel type of therapy called antisense therapy has shown immense potential for the treatment of rare diseases, particularly through single-patient N-of-1 trials. Several N-of-1 antisense therapies have been developed recently for rare diseases, including the landmark study of milasen. In response to the success of N-of-1 antisense therapy, the Food and Drug Administration (FDA) has developed unique guidelines specifically for the development of antisense therapy to treat N-of-1 rare diseases. This policy change establishes a strong foundation for future therapy development, and addresses some of the major limitations that previously hindered the development of therapies for rare diseases.

For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.

Chronic obstructive pulmonary disease (COPD) patients are particularly susceptible to respiratory infections like influenza, which exacerbate symptoms and increase healthcare utilization. While smoking cessation and influenza vaccination are recommended preventive measures, their combined impact on healthcare resource utilization is underexplored. The Charlson Comorbidity Index (CCI) assesses comorbidity burden in COPD patients and may influence healthcare outcomes. We conducted a retrospective analysis of 357 COPD patients, evaluating smoking cessation success over one year and influenza vaccination receipt, stratifying patients by CCI scores. Healthcare utilization outcomes included emergency room visits, hospitalizations, and medical expenses. Results showed that 51.82% of patients quit smoking and 59.66% received influenza vaccination, with higher comorbidity prevalence in advanced COPD stages (p=0.002). Both smoking cessation and influenza vaccination independently correlated with decreased emergency room visits, hospital admissions, days, and costs. Patients who both quit smoking and received influenza vaccination exhibited the lowest healthcare utilization rates. In conclusion, smoking cessation and influenza vaccination significantly reduce healthcare resource utilization in COPD patients, with the combination yielding synergistic benefits, particularly in those with lower CCI scores. Integrating these interventions and comorbidity management in COPD strategies is essential for optimizing patient outcomes and healthcare efficiency.

Lymphocyte collection by apheresis for CAR-T production usually does not include mobilized blood using Granulocyte Colony Stimulating Factor (G-CSF) due to the widespread knowledge that it causes a decrease in the number and functionality of lymphocytes. However, it is used for stem cell transplant, which is a common treatment for hematological malignancies. The growing demand for CAR therapies (CAR-T and NK-CAR), both in research and clinic, makes necessary to evaluate whether mobilized PBSC products may be potential candidates for use in such therapies. This review collects recent work that experimentally verifies the role and functionality of T and NK lymphocytes, and the generation of CAR-T, from apheresis after G-CSF mobilization. As discussed, T cells do not vary significantly in their phenotype, the ratio of CD4+ and CD8+ remains constant and the different sub-populations remain stable. In addition, its expansion and proliferation rate are invariant regardless mobilization with G-CSF, as well as the secretion of proinflammatory cytokines and the cytotoxic ability. Therefore, cells mobilized before apheresis are postulated as a new alternative source of T cells for adoptive therapies that will serve to alleviate high demand, increase availability, and take advantage of the substantial number of existing cryopreserved products.

Histone deacetylase inhibitors (HDACis) are being recognized as a potentially effective treatment approach for peripheral T-cell lymphoma (PTCL), which is a diverse group of aggressive lymphomas with a bleak prognosis. Recent evidence has shown that HDACi are effective in treating PTCL, especially in cases where the disease has relapsed or is resistant to other treatments, and there are few available options. Several clinical trials have demonstrated that HDACi, such as romidepsin and belinostat, can elicit long-lasting positive outcomes in individuals with PTCL, either when used alone or in conjunction with conventional chemotherapy. They exert their anti-tumor actions by regulating gene expression through inhibiting histone deacetylases, which results in the halting of cell division, programmed cell death, and the transformation of cancerous T-cell, as indicated by gene expression profile studies. Importantly, besides clinical trials, real-world evidence indicated that the utilization of HDACi presents a significant and beneficial treatment choice for PTCL. However, although HDACi showed potential effectiveness, they couldn’t cure most patients. Therefore, new combination with conventional drugs as well as new targeted agents are under investigation.

Aiming to improve medical diagnosis and treatment, artificial intelligence (AI) has emerged as a transformational force in the healthcare industry. In this article, we examine how AI is increasingly being used to improve healthcare, with an emphasis on how it is changing medical diagnosis and treatment. We explore the opportunities, threats, and ethical concerns of incorporating AI into healthcare practice. In addition, we feature important AI applications in radiology, pathology, cardiology, and cancer. AI has great potential to improve patient outcomes, diagnostic accuracy, and the ability to provide individualized treatment plans in the future if it is used and refined with care.

Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein. Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

Adherence is vital for medicine to have an effect, yet adherence is considered to be low. However, research into adherence tends to focus on quantitative analysis of performance, something which fails to perceive how people are adherent in their many different environments. As a contribution to gaining a deeper understanding, interviews were held with 30 individuals in UK, Egypt, Kazakhstan and 6 countries in sub-Saharan Africa to understand their perceptions on adherence for a range of drugs, and these were compared with an existing well-regarded list. New reasons for non-adherence were discovered, and a new viewpoint on adherence derived which considers adherence to be a single act and therefore as an individual opportunity to be adherent, permitting greater focus on the enablers and inhibitors of adherence at a point in time.

Adherence to the Mediterranean diet has been shown to lower the risk of developing chronic non-communicable diseases like cardiovascular and neurodegenerative diseases and cancer. Improvements in depression, participation in daily activities in older individuals, weight loss and reduction in adverse pregnancy outcomes are associated with adherence to the Mediterranean diet. The number of studies that have evaluated barriers to the adherence of the Mediterranean diet in the US and in particular, in racial and ethnic minority populations within the US are few. Among Native American and Alaskan Native populations, studies evaluating traditional or alternative Mediterranean diet adherence for chronic non-infectious diseases is unavailable. Mediterranean diet scoring instruments used in studies in European and Mediterranean countries and among white participants in the US fail to capture the dietary patterns of racial and ethnic minority populations. In this narrative review the food components of the traditional Mediterranean diet are discussed, adherence to the Mediterranean diet is examined in Mediterranean and non-Mediterranean countries and barriers preventing adherence to the Mediterranean diet in the US and among racial and ethnic minority populations is reviewed. Recommendations for improving nutrition education and intervention, and increasing adherence and cultural adaptions to the Mediterranean diet are provided.

Ketogenic dietary therapies (KDTs) are an effective and safe non-pharmacological treatment for drug-resistant epilepsy, but adherence can be challenging for both patients and caregivers. In Europe, there are no adequate tools to measure it other than monitoring ketosis. This study aimed to adapt and validate the Brazilian adherence questionnaire, Keto-check, into the Italian version: iKetoCheck. Using the Delphi technique, 12 judges validated the contents through agreement rate and the Content Validity Index (CVI). The iKetocheck was self-completed electronically by drug-resistant epilepsy or GLUT1 deficiency patients within an interval of 15 days to measure its reproducibility. Test-retest reliability was evaluated using Pearson correlation and relative significance test. Exploratory and confirmatory factorial analyses were made using Factor software. The final tool, iKetoCheck, consists of 10 questions with 5-point Likert scale answers. It evaluates various aspects such as informing caregivers about the diet, organization of meals, measurement of ketosis, weighing food consumed, diet negligence, use of carbohydrate-free medications, attending follow-up visits, reading food labels, consulting an expert for dietary concerns, and cooking at home. The factorial analysis resulted in three factors: "attention," "organization," and "precision," with satisfactory results for indices in exploratory and confirmatory analyses. Although higher mean values of ketonemia measurement were observed in patients with a higher adherence score, these values were not statistically significant (p=0.284). In conclusion, iKetoCheck is a valid tool for evaluating KDTs' adherence in Italian drug-resistant epilepsy or GLUT1 deficiency patients. It can provide valuable information to improve patient management and optimize the effectiveness of KDTs.

Introduction: During the COVID-19 pandemic, many countries implemented restrictions, social distancing measures, and lockdowns to limit the spread of the disease. The lockdowns have affected children’s screen time (ST), pain, and physical activity (PA) levels. The present study aimed to explore the relationships between several personal factors during the COVID-19 pandemic. Methods: The caregivers of 329 children (median age=8 years) filled out an online self-reported survey about the children’s PA, ST, and pain before, during, and after the COVID-19 curfew. Spearman’s rank correlation coefficient was used to explore the associations between these variables. Results: After the curfew, pain that existed before the pandemic had a weak negative relationship with PA intensity (-0.11, p=0.04) and a weak positive relationship with ST (r=+0.12, p=0.04). There was a strong positive relationship between ST in all time periods (p&gt;0.01). PA and ST had a weak negative relationship (p&gt;0.05) during the curfew and after the curfew but not before the COVID-19 pandemic. Age had a weak positive correlation with ST in all time periods (p&gt;0.01). In addition, ST was affected by the curfew. Conclusion: The study findings indicated that young children had longer ST during the curfew and after the curfew compared with before the curfew. Increasing PA could lessen children’s ST, which could, in turn, increase the probability that their general pain would decrease.

Iron (Fe) is co-factor for enzymes of the developing brain necessitating sufficient supply. We investigated the effects of administering ferric derisomaltose/Fe isomaltoside (FDI) subcutaneously to Fe deficient (ID) pregnant rats on cerebral and hepatic concentrations of essential metals and gene expression of ferroportin and hepcidin. Pregnant rats subjected to ID were injected with FDI on the day of mating (E0), 14 days into pregnancy (E14), or the day of birth (Postnatal (P0)). The efficacy was evaluated by determination of cerebral and hepatic Fe in pups on P0 and as adults on P70, and the concentration of copper (Cu) and zinc (Zn). Females fed an ID diet (5.2 mg/kg Fe) had offspring with significantly lower cerebral and hepatic Fe compared to female controls fed a standard diet (158 mg/kg Fe). Cerebral Cu increased irrespective of supplying a standard diet or administering FDI combined with the standard diet. Hepatic hepcidin was significantly lower following ID, whereas cerebral hepcidin was virtually undetectable in all experimental groups. In conclusion, administering FDI subcutaneously to ID pregnant rats on EO normalizes cerebral Fe in the fetus, but when applied at later gestational ages, additional Fe to the offspring is needed to normalize cerebral and hepatic Fe.

Rheumatoid arthritis (RA) is an autoimmune disease in which joints are gradually de-stroyed, and early diagnosis and treatment before joint deformation or destruction is im-portant. The detection of novel RA biomarkers in saliva may facilitate the early detection of RA before the onset of disease. In this study, we conducted a comprehensive proteomic analysis of salivary proteins from RA model mice. Proteins were identified by Western blotting and enzyme-linked immunosorbent assay in serum, saliva, and ankle joints from DBA/1JJmsSlc mice, a model of rheumatoid arthritis. Ankle joints and submandibular glands were hematoxylin and eosin stained and immunostained, and the results were compared with those of control mice. Citrullinated α1 antitrypsin (A1AT, 46 kDa) was commonly detected in saliva, serum, and ankle joints of severe RA model mice, and was confirmed by proteome analysis. Western blotting detected a band corresponding to 46 kDa in serum, saliva and ankle joints, and immunostaining of ankle joints with A1AT an-tibody showed a strong positive signal in the synovium. In DBA/1JJmsSlc mice, not only cyclic citrullinated peptide antibodies but also A1AT may be involved in protein citrulli-nation and contribute to the development and severity of RA.

Food Neophobia (FN), defined as the reluctance to eat new or unfamiliar foods, mainly concerns fruit, vegetables, and legumes, typical of the Mediterranean Diet (MD). Considering these premises, this study aimed to clarify the relationship between FN and AMD in a sample of Italian children and their association with some socio-demographic factors and children's nutritional status. A sample of 288 children aged 3-11 years, participated to an assessment carried out with a questionnaire evaluating FN and AMD, respectively with Child Food Neophobia Scale (CFNS) and the KIDMED Test. Most of the sample showed an intermediate (67.3%) or high level of FN (18.1%) with high rates among 6-11 years old children (63.9%) and especially in only-child (50%). The AMD was mostly low (29.5%) or medium (54.8%) and reached lower levels among higher neophobic children (51.9%; p value &lt; 0.05). Present results confirm the study hypothesis that FN is a driver of MD abandonment and show the positive effects on children's eating habits of having siblings. Finally, this study proves the relevance of adopting effective feeding strategies against FN to avoid its maintenance in adulthood and detrimental effects on future overall health and well-being.

Background: The relationship between adherence to the Mediterranean Diet (MD) and both physical fitness (PF) and physical activity (PA) level has been analysed in several studies. The aim of this research was to describe, compare and analyse the level of PF and PA in schoolchildren aged 6-13 in the Region of Murcia, according to adherence to the MD. Methods: A descriptive and cross-sectional study was performed. A total of 370 schoolchildren (44.9% girls) aged 6-13 (8.7±1.8) from six primary schools in the Region of Murcia (Spain). Results: Only 25.9% of the schoolchildren had optimal adherence to the MD. Regarding the scores of the different PF tests in MD groups, only statistically significant differences were found for CRF (p=0.048) in boys. PA level, showed statistically significant differences in both boys (p=0.040) and girls (p=0.016). A positive relationship was found between the KIDMED index and CRF (ρ=.127), standing broad jump (ρ=.133) and PA level (ρ=.235). A higher probability of having a greater CRF (OR=1.17; CI95%=1.02–1.34) and PA level (OR=7.84; CI95%=2.84–21.60) was found in High MD group. Conclusion: These results suggest that an optimal adherence to the MD is associated with higher CRF and PA level in the selected schoolchildren.

Spectral photon counting cone-beam CT imaging is challenged by individual pixel response behaviour, which leads to noisy projection images and subsequent image artefacts like rings. Existing methods to correct for this either use calibration measurements, like signal-to-thickness calibration (STC), or perform post-processing ring artefact correction of sinogram data or scan reconstructions, without taking the pixel response explicitly into account. Here we present a novel post-processing method (DAC-shifting), which explicitly measures the current pixel response using flat field images, and subsequently corrects the projection data. The DAC-shifting method was evaluated with a repeat series of spectral photon counting imaging (Medipix3) of a phantom with different density inserts, and in iodine K-edge imaging. The method was also compared against PMMA based STC. The DAC-shifting method was shown to be effective in correcting individual pixel response, and was robust against detector instability. On the contrary, STC correction showed varying results, which was almost as good as DAC-shifting when data was acquired just after STC calibration, but worse with larger time differences. In K-edge imaging, DAC-shifting provides a sharper attenuation peak, and more uniform CT values, which is expected to benefit iodine concentration quantification.

Objective: To explore the inter-rater reliability of the Measurement Of adherence Via Exercise Demonstration (MOVED) adherence tool. Design: Reliability study of a patient adherence measurement tool.Setting: Simulated physiotherapist-patient consultations. Participants: Sixteen experienced physiotherapists rated patient adherence to exercise. Interventions: N/A Main Outcome Measure: Inter-rater reliability of MOVED.Methods: The MOVED tool consists of two parts. Part one asks patients to self-report their adherence to exercise dose (including number of completed sessions, sets and repetitions in the last seven days). Part two asks patients to demonstrate each exercise. Component scores are totalled to give an overall level of patient adherence to each exercise.Participants were provided with a copy of five physiotherapist-prescribed exercises. Participants were then shown five corresponding video vignettes of simulated physiotherapist-patient consultations where patients were asked to self-report exercise frequency, sets and repetitions and demonstrate each exercise within the context of a consultation. Participants were asked to rate the level of patient adherence to each of the five exercises using the MOVED tool. Inter-rater reliability of MOVED scores was assessed using Intraclass Correlation Coefficient (ICC) and 95% Confidence Intervals. Results: The ICC of part one (self-report) was .90 (95%CI .74-.98), part two (demonstration) was .98 (95%CI .94-.99) and total score was .96 (95%CI .88-.99), demonstrating excellent inter-rater reliability. Conclusion: The MOVED tool, which can highlight whether patients are adhering to exercise technique as well as exercise dose, may provide clinicians and researchers with a more robust measure of exercise adherence when compared with other measures currently available.

Beta thalassemia is an inherited blood disorder that results in inefficient erythropoiesis due to genetic mutation that leads to reduction or absence of the hemoglobin beta-globulin protein. Approximately 8.5% of UAE residents suffer from β-thalassemia, a significant health and financial problem. The treatment options available for β-Thalassemia major are limited and associated with a wide range of complications. β-thalassemia gene therapy is emerging as a potential novel treatment option that eliminates the complications caused by the current long-term treatment modalities and the associated economic burden. This paper reviews the scientific literature related to emerging gene-therapy for β-Thalassemia by analyzing all the articles published from January 2010 to December 2023 in the English language on Databases like PubMed, Scopus, ProQuest, and CINAHL. The use of gene therapy has demonstrated promising outcomes for a permanent cure of β-Thalassemia. ZYNTEGLO (Betibeglogene autotemcel) is the only cell-based gene therapy which was approved by the FDA on 19th August, 2018. To conclude, Gene therapy is an innovative solution. It demonstrates a promising future, but does come with its own set-backs and is something that must be tackled in-order to revolutionize it in the medical world. FDA approved ZYNTEGLO is a potentially one-time curative treatment for β-Thalassemia. Although cutting-edge, its use is limited because of the high cost; a price of $2.8million per patient.

Evidence suggests that COVID-19 infection can cause lasting health consequences. Multidiscipli-nary rehabilitation services have been recommended to reduce the sequalae. However, the effec-tiveness of physical exercise interventions remains insufficiently documented. The aim of this study was to develop and implement a specific and well tolerated protocol-based, intervention to reduce muscle weakness in older adults impacted by COVID-19. Forty six older adults random-ized into Intervention and Control Groups. Isometric and isokinetic strength assessments were conducted for selected muscle groups using JBA Staniak® torquemeter and Biodex System 3 dy-namometer. Functional abilities were evaluated with the Time Up and Go test and Chair Stand Tests. Men in intervention group demonstrated a significant improvement in static conditions for knee flexors (KF), trunk extensors (TE) and trunk flexors (TF) and in dynamic conditions for knee extensors (KE). Women in intervention group showed significant improvement in static condition for EF, KF, TE and TF and in dynamic for a KE and for a KF. The interaction GROUP x TESTING SESSION was significant for Chair test (s) and Chair test (n). Our results demonstrate the effec-tiveness of a well-tolerated, protocol-based approach that can be used to diminish long lasting functional deficits in post-covid survivors.

Pulmonary complications are frequently observed in patients with ulcerative colitis (UC), with large airway disease being the most prevalent manifestation. In this case study, we explore the potential for Immunosuppressant, a monoclonal antibody, to induce pulmonary hemorrhage—a side effect not previously documented with its use. The subject, a young male in his twenties with a six-year history of UC, tragically died suddenly. Found in a pool of blood without external injuries, extensive post-mortem examinations were required to determine the cause of death. The patient had been on biologic therapy, receiving Immunosuppressant intermittently over the past two years, including an infusion five days prior to death. External examination revealed bloody, pinkish foamy material expelling from his nose and mouth. An autopsy supported an atypical presentation of UC, while histopathology confirmed diffuse pulmonary hemorrhage, marked by edema and emphysematous changes. Additionally, there was a notable lymphomonocytic infiltration around the arterial walls, and signs of bronchiolitis and focal pleural fibrosis were evident. We concluded that the cause of death was Diffuse Alveolar Hemorrhage (DAH), directly associated with the recent administration of Immunosuppressant. This finding underscores the need for vigilant pulmonary monitoring in patients treated with monoclonal antibodies to promptly identify and manage potential fatal adverse reactions.

Telomeres, located at the ends of each chromosome play a vital role in determining cellular fate and aging. Accelerated shortening of telomeres may also result in accelerated aging and occurrence of age-related degenerative diseases. Anti-aging treatments may help in increasing the telomere length along with improving quality of life, reducing dependency for daily life activities, increasing life expectancy and reducing the risks associated with aging. In this study, we evaluated the effect of anti-aging integrative therapy in 36 individuals. The treatment included a combination of HBOT, ozone therapy, colon hydrotherapy, etc. Telomere length was used as a biomarker for objectively quantifying the outcome of the treatment. The effect of treatment was also assessed on various aging symptoms. At the end of the treatment, it was found that that 97.22% individuals showed an increase in telomere length with an average increase of 0.43 Kbp and 94.44% individuals showed reduced biological age with an average decrease of 3.8 years. These improvements were statistically significant. Improvements were also recorded in the majority of the symptoms. No major adverse events were observed. These results indicate that antiaging integrative therapy has the potential to reverse aging symptoms, cellular aging and improve quality of life.

Greek roots: "phos" (φῶς) - means "light" and "dynamis" (δύναμις) - means "force" or "power". Photodynamic therapy (PDT) is an innovative treatment method based on the ability of photosensitizers to produce reactive oxygen species after exposure to light of a specific wavelength range, either in the visible or near infrared range. This process results in damage to pathological cells, such as cancer cells, while minimizing the impact on healthy tissues. PDT is a promising direction in the treatment of many diseases, with particular emphasis on the fight against cancer and other diseases asso-ciated with excessive cell growth. The power of light contributed to the creation of phototherapy, whose history dates back to ancient times. It was then noticed that some substances exposed to the sun have a negative effect on the body, while others have a therapeutic effect. This work provides a detailed review of photodynamic therapy, from its origins to the present day. It is surprising how a seemingly simple beam of light can have such a powerful healing effect, which is used not only in dermatology, but also in oncology, surgery, microbiology, virology, and even dentistry. However, despite promising re-sults, photodynamic therapy still faces many challenges. The availability of this thera-py is limited due to the small number of centers offering this type of treatment and the high costs, which may be unaffordable for many patients. Moreover, photodynamic therapy requires further research and improvement.

Background: Regardless of the indisputable benefits of insulin therapy, initiating insulin for diagnosed children with diabetes might be intimidating for parents. This study assesses the experience, fears, barriers and adherence to insulin use among the parents of diagnosed children with diabetes. Methods: A cross-sectional online survey was utilized for data collection from 218 participants between February and March 2023 in Jordan. The survey consisted of six sections to evaluate and assess: sociodemographic for both children with diabetes and their parents, the experience of using the insulin, the diabetes fear of self-injecting questionnaire (D-FISQ), the barriers for insulin administration including both sociocultural and other insulin-related factors, and insulin adherence. Results: More than 80% of the participants perceived a number of sociocultural barriers to insulin administration such as the tendency for addiction, lower efficiency of insulin than oral medication, and preference for complementary medicine over insulin. More than two-thirds of the participants complained of insulin-related barriers such as infections and sudden death in addition to learning the correct injection method. The general fear level was low, 8.56±7.87 (out of 45); however, more fear of insulin injection and self-testing was significantly associated with both sociocultural and insulin-related barriers, especially at the younger age. Conclusion: The results of this study indicated that parents have several barriers to insulin administration, mainly related to insulin injection. Therefore, more awareness about insulin therapy can help adjust the cooperation of patients, acceptance of treatment, ending with improving the quality of life and well-being.

Abstract: Objective: This study aimed to estimate adherence to methotrexate in patients with rheumatoid arthritis and identify specific nonadherence risk factors. Methods: A cross-sectional study included 111 patients (age mean 56.2±10.6 years, 78.4% female, and disease duration mean 6 (3-13) years). Three adherence self-assessment questionnaires were used: the Compli-ance-Questionnaire-Rheumatology (CQR19), the Medication Adherence Reports Scale (MARS-5), and the Visual Analogue Scale (VAS). We also collected demographic data, disease and treatment characteristics, and anxiety/depression estimation results (Hospital Anxiety and Depression Scale- HADS). Results: Adherence was identified in 48.6% of patients (COR19), 70.3% (MARS-5), and 82.9% of patients in the VAS questionnaire. All three questionnaires displayed a significant positive mutual correlation: CQR19 with MARS-5 and VAS (r =0.364, r=0.329 respectively, p<0.001 for both), between VAS and MARS-5 score (r=0.496, p<0.001). A significant positive prediction was shown for urban residence (0.347 (0.134-0.901), p=0.030), using the MARS-5 scale, female sex (0.264 (0.095-0.730), p=0.010) according to CQR19 and for a dose of methotrexate (0.881 (0.783-0.992), p=0.036) in VAS scale, while negative prediction were shown for comorbidity number (3.062 (1.057-8.874), p=0.039), and depression (1.142 (1.010-1.293), p=0.035) using MARS-5 scale and for older age (1.041 (1.003-1.081), p=0.034) according to CQR19. The use of steroids was a significant positive predictor in all three questionnaires and remained an independent predictor for metho-trexate adherence in multivariant logistic regression. Conclusion: We showed nonadherence to methotrexate in a significant number of patients using all three questionnaires. Concomitant steroid therapy emerged as an independent positive predictor for adherence.

This study unveils verapamil's compelling cytoprotective and proliferative effects on pancreatic β-cells amidst diabetic stressors, spotlighting its unforeseen role in augmenting cholecystokinin (CCK) expression. Through rigorous investigations employing MIN6 β-cells and zebrafish models under type 1 and type 2 diabetic conditions, we demonstrate verapamil's capacity to significantly boost β-cell proliferation, enhance glucose-stimulated insulin secretion, and fortify cellular resil-ience. A pivotal revelation of our research is verapamil's induction of CCK, a peptide hormone known for its role in nutrient digestion and insulin secretion, which signifies a novel pathway through which verapamil exerts its therapeutic effects. Furthermore, our mechanistic insights reveal that verapamil orchestrates a broad spectrum of gene and protein expressions pivotal for β-cell survival and adaptation to immune-metabolic challenges. In vivo validation in a zebrafish larvae model confirms verapamil's efficacy in fostering β-cell recovery post-metronidazole inflic-tion. Collectively, our findings advocate for verapamil's reevaluation as a multifaceted agent in diabetes therapy, highlighting its novel function in CCK upregulation alongside enhancing β-cell proliferation, glucose sensing, and oxidative respiration. This research enriches the therapeutic landscape, proposing verapamil not only as a cytoprotector but also as a promoter of β-cell re-generation, thereby offering fresh avenues for diabetes management strategies aimed at pre-serving and augmenting β-cell functionality.

Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory disease in infants and young children worldwide. Two vaccines targeting the elderly and pregnant women have been recently approved employing the prefusion form of the RSV-fusion protein (F). However, there are currently no vaccines for infants. Studies have shown a fusion-inactive prefusogenic F form is significantly more immunogenic and produces higher antibody titers to both the prefusion and postfusion structures of the F protein. Here we have developed RSV virus-like particles (RSV-VLPs) consisting of prefusogenic F, RSV glycoprotein and matrix proteins, produced them using the baculovirus expression system, and studied their protective efficacy in Balb/c mice. Morphology and successful assembly of VLPs were confirmed by transmission electron microscopy and western blot. Mice immunized with VLPs developed high levels of serum IgG and neutralizing antibodies as compared with mice immunized with inactivated virus. The VLP vaccine also induced higher levels of IFNγ and IL4, elicited limited proliferation of CD4+ and CD8+ T cells but higher cytotoxic-T-lymphocyte responses. VLP immunization abolished lung pathology in the mice after RSV challenge. Overall, our results indicate that RSV-VLPs consisting of prefusogenic F, glycoprotein and matrix proteins are a potential vaccine candidate against RSV.

Biochar is a carbonaceous material derived from the thermochemical conversion of biomass under oxygen-lean conditions. Its properties render it many applications in agriculture, environmental remediation, and catalysis. Commonly produced by pyrolysis under a nitrogen atmosphere, the biochar composition is influenced mainly by residence time, heating rate, and process temperature. The existing literature primarily assesses biochar properties, such as ultimate, proximate, calorific, porosity, and combustibility, generated under various thermo-conversion conditions. However, there is a notable lack of sufficient investigation and attention given to the practical application of biochar. This article seeks to bridge that gap by enhancing the comprehension of the necessary experimental assessment for specific biochar applications and proposing process optimization methods using Multi-Criteria Decision Analysis (MCDA). By delving into these aspects, the study offers a concise overview of biochar production and presents a comprehensive panorama based on articles and patents. Additionally, the research explores the physicochemical characterization techniques associated with biochar and its various applications in conjunction with MCDA. This comprehensive approach aims to uncover valuable insights that could further advance the practical and sustainable utilization of biochar in a wide range of fields.

Integrated crop-livestock production (ILP) is an interesting alternative for more sustainable soil use. However, more studies are needed to analyze soil pore properties under ILP at the micrometer scale. Thus, this study proposes a detailed analysis of soil pore architecture at the micrometer scale in three dimensions. For this purpose, samples of an Oxisol under ILP subjected to minimum tillage (MT) and no-tillage (NT) with ryegrass as cover crop (C) and silage (S) were investigated. The soil micromorphological properties of the soil were analyzed using X-ray microtomography. The MT(C) system showed the highest values of porosity (c. 20.4%), connectivity (c. 32.8×103), volume (c. 26%), and number of pores (c. 32%) in a rod-like shape. On the other hand, the MT(S), NT(C), and NT(S) systems showed higher tortuosities (c. 2.2, c. 2.0, and c. 2.1) and lower pore connectivities (c. 8.3×103, c. 6.9×103, and c. 6.2×103), especially in S use. Ellipsoidal and rod-shaped pores predominated over spheroidal and disc-shaped pores in all treatments. The results of this study show that the use of ryegrass as a cover crop improves soil physical properties, especially in MT. For S use, the type of soil management (MT or NT) did not show any differences.

Background: Early postoperative airway management after laryngo-tracheal surgery is crucial. Acute respiratory failure due to glottis’ oedema may occur, requiring reintubation. This can prolong ventilatory assistance, jeopardizing the anastomosis. To date, only judicious steroid administration and fluid management are available to avoid more invasive procedures. High-Flow-Oxygen-Therapy(HFOT) is a noninvasive O2 support method providing humidification, warmed air, Positive-End-Expiratory-Pressure(AIRVO2). No data exist about HFOT use to prevent early complications after laryngo-tracheal surgery. Methods: Between Sept.2020-Sept.2022, 107 consecutive patients underwent laryngo-tracheal surgery received HFOT(Group A). Data and long-term results were compared with those of 80 patients operated between Sept.2018-Aug.2020(Group B), when HFOT was not available. All patients were operated in a single center. No pre- or post-operative settings changed, except for HFOT introduction. We analyzed and compared the risk for “delayed” reintubation (unexpected reintubation within the first 24-48 hours after extubating/laryngeal mask removal) in the two groups. Results: No patients reported HFOT-related adverse events. Control group(B) presented “delayed” reintubation in 37% (p= 0.027), Intensive Care Unit admission in 67%(p=0.005) and longer hospital stay(p=0.001) compared to HFOT group(A). Minor complications rate was 3% in both group and overall mortality was 0%. Re-stenosis was described in 4.6% of HFOT group, without a statistically significant difference (p=0.7006). Conclusions: Our study is the first to investigate HFOT use in patients undergoing laryngo-tracheal surgery, potentially representing a consistent innovation in the peri-operative management of these patients. With the limit of a retrospective series, we would suggest HFOT use for preventing post-operative reintubation rate, possibly reducing ICU admission and hospital stay.

Background and Objectives: Cancer as the second leading cause of death in the United States poses a huge healthcare burden. Barriers to access to advanced therapies influence the outcome of cancer treatment. In this study, we examined whether insurance types affect the quality of cancer clinical care regarding access to an important monoclonal antibody, ramucirumab. Materials and Methods: Data for 13,340 cancer patients with Purchased or Medicaid insurance from the All of Us Database were collected for this study. The Chi-square test of proportions was employed to determine the significance of patient cohort characteristics and ramucirumab usage between Purchased and Medicaid insurance groups. The independent t-test was utilized to assess the influences of other determinants on insurance types. Results: Cancer patients who are African American, with lower socioeconomic status, or with lower educational attainment are more likely to be insured by Medicaid. Analysis of survey questions demonstrated the relationship between income and education level with insurance type as Medicaid cancer patients were less likely to receive primary care and specialist physician access and more likely to request lower cost medications. In addition, those with Medicaid insurance were identified to have poorer access to expensive therapeutics like ramucirumab compared to those with Purchased insurance.  Conclusions: The inequities of the US healthcare system are observed for cancer patient care; access to physicians and therapeutics are highly varied and dependent on insurance types. Socioeconomic status determines insurance type, which unfortunately generates a significant impact on cancer treatment and disease outcome.

Objectives We tested the hypothesis that poor adherence is associated with a greater risk of alcohol-caused mortality and morbidities within the first year of discontinuing this medication. Materials and Methods Retrospective cohort study of 3319 individuals who received Acamprosate® in the East of Scotland in a 10-year period using a health informatics approach with record linkage of dispensing data, hospital utilization (SMR) and General Register Office of Scotland (GROS) data. Primary outcome was adherence between one to six months of initiating Acamprosate® medication. Secondary outcome was all cause morbidities and mortality. Results Of the total 3319 individuals identified, good adherence index of >80% was found in 59% of those prescribed Acamprosate® after three months and 6% after six months. There were significant linear trends of poorer adherence with increased risk of alcohol-caused mortality (HR1.2), medical morbidities especially neoplasm (HR 4.1|) and poisoning (HR 1.4) and psychiatric morbidities especially stress (HR 35.1), psychotic (HR 5.6) and neurotic disorders and directly alcohol induced conditions (7.4 HR) after adjustment for other factors within a one-year period of initiation of Acamprosate® treatment. Discussion and Conclusions Further exploratory studies using this digitalized approach should be encouraged in order to capture role of compliance to Acamprosate® and other types of medication that are known to reduce relapse into alcohol dependence and its direct relationship to mortality and morbidities in this population.

Background: Chronic Heart failure (CHF)constitutes a major health problem, representing the leading cause of hospitalization in people over 65 years old. Several studies have associated the Mediterranean diet with a cardioprotective function, improving prognosis in patients with high cardiovascular risk. Our main objective is to determine whether greater adherence to the Mediterranean diet is associated with a lower severity of CHF, depending on the number of heart failure decompensations and complications of the disease. Methods: The study was a single-center restrospective cohort study conducted at the Virgen del Rocío Hospital (Seville). Adherence to a Mediterranean diet was determined by the Mediterranean Diet Adherence Screener (MEDAS) in patients with chronic heart failure in a state of clinical stability, and their cardiac and analytical profiles were evaluated. Results: Seventy-two patients were included (35 with high adherence to the Mediterranean diet and 37 with low adherence). The average age was 81.29 ± 0.86 years. A trend towards fewer cardiac decompensations (1,49 ± 0,14 vs 1,92 ± 0,17), p= 0,054) and lower NT-proBNP values 2897,02 ± 617,16 vs 5227,96 ± 1047,12; p = 0,088) was observed in patients with high adherence compared to those with low adherence to the Mediterranean diet. Conclusions: Our results suggest that patients with CHF and high adherence to the Mediterranean diet have a tendency towards improved cardiac profile, indicated by fewer decompensations and lower NT-proBNP levels. Future clinical trials are needed to substantiate these hypotheses.

Globally, between 10% and 15% of couples experience infertility. Given the high demand for Assisted Reproductive Techniques (ART), there is growing interest in exploring modifiable factors influencing their outcomes. In this context, the objective of this review was to investigate the impact of adherence to the Mediterranean Diet (MD), recognized for its benefits in reproductive health, on ART outcomes. Methodology: A systematic review was conducted following the PRISMA methodology. International databases were consulted, selecting studies published between 2010 and 2023, in English and Spanish, involving patients aged 18-55, and examining intermediate and/or clinical outcomes of ART. Systematic reviews, meta-analyses, and animal studies were excluded. Results: Of the 9 included articles, 5 found statistically significant associations between adherence to the MD and positive outcomes in ART, such as a higher number and quality of embryos, clinical and biochemical pregnancy, and live births. However, other studies found no such associations. Conclusions: There is a potential association between adherence to the MD and ART outcomes. The evidence is very limited, necessitating further investigation.

(1) Background: Rational use of medicines (RUM) and their assessment is important to ensure optimal use of resources and patient care in hospitals. These assessments are essential to identifying practice gaps for quality improvement. (2) Methods: Assessment of adherence to WHO/ International Network for Rational Use of Drugs core prescribing indicators among out-patients in 2021 was conducted at the University Hospital of the Kwame Nkrumah University of Science and Technology in the Ashanti region of Ghana. We reviewed electronic medical records (EMR) of 110,280 patient encounters in the year which resulted in 336,087 medicines prescribed. (3) Results: The average number of medicines prescribed per encounter was 3 with generics being prescribed in 76% of prescriptions. Injections were prescribed in 7% of encounters while 90% of medicines were from Ghana’s Essential Medicines List 2017. (4) Conclusions: With the exception of patient encounters with injections, all prescribing indicators assessed in this study did not meet WHO optimum levels providing targets for quality improvement in RUM. Implementing prescribing guides and policies, regular audits and feedback as well as continuous professional development training may help to improve prescribing practices in the hospital.

Background: We prepared reference materials of fentanyl and amphetamines in hair, and established methods for the certification of reference materials of fentanyl and amphetamines in hair samples. Methods: Hair samples containing 15 drugs were prepared by immersion method (water-dimethylsulfoxide). On the basis of single-factor experiment, Box-Behnken design-response surface was used to optimize the pre-treatment conditions of samples. In MRM/SIM mode, 15 drugs were quantitatively analyzed by LC-MS/MS and GC-MS/MS methods. Results: The contents of 15 drugs in the mixed hair samples were: 1.050 ng mg-1~7.771 ng mg-1, RSDs&lt;7%(n=11). The results showed that the two analytical methods developed were highly sensitive (LODs as low as 0.05 pg mg-1), reproducible (intra-day and inter-day precision RSDs were&lt;10%) and accurate. F-test was performed on the prepared hair samples and the results showed that the homogeneity of the prepared hair samples was good. Conclusions: The established methods were used for the detection of fentanyl and amphetamine drugs in human hair, with high sensitivity, accuracy and specificity. It can be used as a certified method for the development of fentanyl and amphetamine matrix certified reference materials. The developed hair reference materials are expected to be applied in forensic drug abuse detection and laboratory quality control.

The comorbidity of osteoarthritis and type 2 diabetes mellitus represents a complex clinical challenge and complicates patient management due to the interplay of overlapping pathophysiological mechanisms. The research aimed to analyze the exacerbation of clinical symptoms and biochemical markers in patients with osteoarthritis and type 2 diabetes mellitus compared to those with osteoarthritis. We utilized various assessment methods to measure the patient cohorts' inflammation, oxidative stress, and glycemic control. The study also involved the administration of alpha-lipoic acid to patients with comorbid osteoarthritis and type 2 diabetes mellitus and monitored its effects on joint function, inflammatory markers, oxidative stress levels, and glycemic control. Our findings revealed that the presence of type 2 diabetes mellitus significantly intensified osteoarthritis symptoms and altered biochemical markers, including increased inflammation, elevated oxidative stress, and disrupted immunological balance. The treatment with alpha-lipoic acid resulted in improved joint function, reduced inflammation and oxidative stress levels, and better glycemic control. Additionally, it was identified several potential predictors for developing osteoarthritis and type 2 diabetes mellitus comorbidity. The results underscore the detrimental impact of type 2 diabetes mellitus on osteoarthritis and highlight the beneficial effects of alpha-lipoic acid in alleviating some of the adverse consequences associated with this comorbidity. Nonetheless, further research is necessary to comprehensively evaluate the therapeutic efficacy of alpha-lipoic acid and its long-term effects on managing comorbidity of osteoarthritis and type 2 diabetes mellitus.

This study aimed to investigate the knowledge of patients with hypertension about their condition, adherence to antihypertensive medication, and the factors influencing it. A cross-sectional study was conducted in two cardiology outpatient clinics of two tertiary hospitals, in Greece. The study included 188 patients diagnosed with hypertension. The patient’s knowledge about their disease and adherence to medication were assessed by using the HK-LS and A-14 scales, respectively. Patients had sufficient knowledge levels about their disease, but significantly low levels of adherence to medication. Patients with higher knowledge levels were more adherent to medications [r(188) = 0.885, p &lt; 0.001]. By using multivariate analysis, higher age (p = 0.018), residence in a more populous area (p = 0.041), more years with the disease (p = 0.012), and a lower number of medications (p = 0.03) were associated with higher levels of knowledge. Conversely, younger age (p = 0.036), lower educational levels (p = 0.048), fewer years with the disease (p = 0.001), and a higher number of medications (p = 0.003) were associated with lower adherence to medication. The Greek patients' hypertension knowledge was sufficient, however, adherence to medication was significantly low. Healthcare managers could utilize our findings to design targeted interventions for improving adherence to medication for these patients.