Immunotherapy, particularly Immune Checkpoint Blockade (ICB), has demonstrated significant efficacy in treating melanoma in recent years. However, accurately predicting treatment success and avoiding ineffective therapies remains an unresolved challenge. Therefore, this study aims to develop statistical models utilizing neural networks to forecast the effectiveness of immune checkpoint therapies for melanoma patients. Our models primarily rely on Artificial Neural Networks (ANN) to anticipate both Overall Survival (OS) and Progression-Free Survival (PFS) among melanoma patients undergoing anti-CTLA4 and anti-PD1/anti-PDL1 therapy. We incorporate gene expression data, measured in Transcripts per Million (TPM), derived from bulk tumor RNA-sequencing datasets. Additionally, clinical variables such as gender, age, and treatment type are factored into our analysis. The ANN underwent optimization to attain the highest feasible precision in anticipating the predetermined survival outcome. Issues stemming from high-dimensional data, such as overfitting, were tackled through regularization and feature selection methods. Consequently, the ANN-based model incorporating feature selection exhibited the capacity to forecast survival (PFS) in response to ICB therapy with a maximal precision of 86%. Conversely, the ANN lacking feature selection but incorporating regularization achieved accuracies of up to 72% for PFS and 71% for OS, correspondingly. In order to confront the challenge posed by limited patient samples and to assess replicability, the model underwent training and validation based on the amalgamation of all five datasets. However, this amalgamation failed to enhance predictive performance, necessitating further investigations.

In this study, we aim to explore whether rephrasing enhances the performance of advanced question answering systems in terms of accuracy. Initially, we analyze the effectiveness of Bidirectional Encoder Representations from Transformers (BERT)—a widely used pre-trained language model—when presented with rephrased questions and documents containing distracting details. Our findings reveal that BERT exhibits excessive sensitivity to such instances, prompting us to investigate potential strategies for mitigating this sensitivity. To address the observed decline in performance, we propose a refinement approach for BERT, incorporating techniques such as data augmentation and multitask learning. Specifically, given a question and its context, we generate a series of paraphrases through back-translation. Alongside minimizing the loss between the predicted answer distributions for the original questions—we also minimize the supervised loss associated with the augmented questions. Furthermore, we introduce an auxiliary objective aimed at minimizing the unsupervised loss between the answer distributions of the original and augmented questions. Notably, this auxiliary loss is unsupervised, as it does not directly rely on labels corresponding to the augmented examples. To compute this unsupervised loss, we employ measures such as symmetric Kullback-Leibler divergence and the Jensen-Shannon distance, serving as regularization techniques for the model. The findings revealed that the supervised model exhibited superior performance compared to both the original and our proposed model. However, our proposed model demonstrated a nearly 2% enhancement in both Exact Match (EM) and F1 scores when tested on a paraphrased development set that we formulated. This suggests the potential effectiveness of our proposed approach in enhancing model accuracy and performance.

The primary aim of this study is to investigate the relationship of the Mediterranean diet (MD) with metabolic syndrome (MetS) and its components in Caucasian subjects between 35 and 74 years. The secondary aim is to analyze sex differences. Methods: A cross‑sectional trial. This study utilized data from the EVA, MARK, and EVIDENT studies, a total of 3417 subjects with a mean age of 60.14±9.14 years (57% men). MetS was defined based on the Joint Scientific Statement National Cholesterol Education Program III. Waist circumference, blood pressure, fasting plasma glucose, and lipid profile were measured. Adherence to the MD was assessed with the 14-item Mediterranean Diet Adherence Screener (MEDAS) questionnaire used in the PREDIMED study. Good adherence was considered when the MD value was higher than the median value. Results: The mean value of the MEDAS questionnaire was 5.83±2.04; (Men 5.66±2.06 and women 6.04±1.99; p<0.001). Adherence to the MD was observed by 38.6% (34.3% men and 40.3% women; p<0.001). MetS was observed in 41.6% (39.0% men and 45.2%women p<0.001). In the multiple regression analysis after adjusting for possible confounders, the mean MD value showed a negative association with the number of MetS components per subject (β=-0.336), and with the different components of MetS: Systolic blood pressure (β=-0.011), Diastolic blood pressure (β=-0.029), glycemia (β=-0.009), Triglycerides (β=-0.004), Waist circumference (β=-0.026), except with the HDL-cholesterol value which showed a positive association (β=0.021); (p<0.001 in all cases). The adjusted logistic regression models showed that an increase in MDA decreases the probability of MetS (OR =0.56) and its components: blood pressure ≥130/85 mmHg (OR = 0.63), fasting plasma glucose ≥100 mg/dL (OR = 0.62); triglycerides ≥150 mg/dL (OR = 0.65); waist circumference ≥88 cm in women and ≥102 cm in men (OR = 0.74), and increases high-density lipoprotein cholesterol <40 mg/dL in men or <50 mg/dL in women (OR = 1.70); (p<0.001 in all cases). The results by sex were similar, both in multiple regression and logistic regression. Conclusion: The results of this study suggest that a greater adherence to the Mediterranean diet decreases the probability of presenting Mets globally and by sex.

The marathon sport events and those who participate in these have grown over the last years reflecting notably an augmentation of women and master runners participation. The aim of the present narrative review was to briefly present the results of studies on anthropometric, physiological and training characteristics, as well as predictors of performance, in marathon runners. It was observed that performance was better in runners with small body weight, body mass index, body fat percentage, and rate of endomorphy. With regards to physiology, an increased maximal oxygen uptake, anaerobic threshold, and improved running economy could result in faster race time. The training variables that could predict performance involved weekly training volume (distance) and intensity (running speed), as well as history of training (years). A combination of these three broad categories of characteristics may offer an approximate estimation of the race speed considering that other aspects (e.g., nutrition, biomechanic and motivation) influence race performance, too. In summary, the findings of the present study provided an overview of anthropometric, physiological and training characteristics associated with marathon race time; thus, an optimization of any of these characteristics would be expected to improve race time.

Accurate clinical diagnosis of patients presenting to primary care settings with acute sore throat remains challenging, often resulting in the over-prescribing of antibiotics. Using point-of-care tests (POCTs) to differentiate between respiratory infections is well-accepted, yet evidence on the application within primary care is sparse. We assessed the application of testing patients (n=160) from three family practices with suspected Streptococcal infections using rapid molecular tests (ID NOW Strep A2, Abbott). In addition to comparing clinical evaluation and prescription rates with either usual care or with testing, patients and staff completed a questionnaire about their experience of molecular POCT in primary care. The immediate availability of the result was important to patients (100%) and staff (≈90%) stated that molecular testing improved quality of care. Interestingly, only 22.73% of patients with a Centor score >2 tested positive for Strep A and overall, less than 50% of Centor scores 3 and 4 tested positive for Strep A with the ID NOW testing platform. The addition of rapid molecular POCTs to clinical assessment resulted in a 55- 65% reduction in immediate and deferred antibiotic prescriptions. The intervention was popular with patients and medical staff but was associated with increased cost and a longer appointment length.

We present a case report of a young patient with pectus carinatum who experienced a small right apex pneumothorax and exhibited Brugada patterns on electrocardiogram tracing. This is the first clinical case reporting Brugada pattern presentation in both a patient with pectus carinatum and a small pneumothorax. We conducted a clinical, anatomical, and electrocardiographic analysis to explore a physiopathological explanation for these findings, considering our patient had no history or clinical signs of Brugada Syndrome. We conclude that: 1. Pectus carinatum may create a window that facilitates the less resistive measurement of cardiac action potentials; 2. Small pneumothoraces can induce modifications in the cardiac electrical signal detected by surface electrodes, and pectus carinatum could unmask these modifications; and 3. Surface electrodes may measure subepicardial potentials that include and are modified by adjacent pericardial tissues, potentially resulting in alterations in transmural potential differences, thus producing fictitious Brugada patterns. Similarly, there is a possibility that the right ventricular outflow tract may be included within the subendocardial potentials.

A previous report showed that the urine output of HPLBII-P in patients with diabetes mellitus and SARS-Cov-2 infection was increased as a sign of glomerular dysfunction. . The aim of this report was to investigate the relation of urine output of HPLBII-P to diabetes mellitus in two large community-based elderly populations i.e. the ULSAM and PIVUS cohorts. Methods HPLBII-P was measured by ELISA in the urine of a community-based cohort of 839 men (ULSAM) collected at 77 years of age and in urine of a community-based cohort of 75-year-old men, n=387, and women, n=401 (PIVUS). KIM-1, NGAL and Albumin were measured in urine and Cathepsin S and Cystatin C in serum. Results HPLBII-P was significantly raised among males with diabetes in the ULSAM (p

Graves' disease (GD) is an autoimmune disorder in which Thyrotropin Receptor Antibodies (TRAb) continuously stimulate thyroid receptors, leading to excessive production of thyroid hormones. TRAb also affect the orbital tissues, causing Graves' ophthalmopathy. Treatment to control Graves' disease consists of antithyroid drugs, radioiodine and thyroidectomy, and through such treatments, TRAb is reduced and the disease is alleviated. The mechanism by which TRAb, which play a critical role in the pathogenesis of Graves’ disease, decreases after GD treatment is still unknown. This paper presents a theoretical mechanism of how GD patients maintain a vicious cycle and how GD treatment can reduce the TRAb levels and breaks the cycle using stress-based ideas.

The oviparous blow fly Calliphora vicina has shown potential as a managed pollination species to support honeybee (Apis mellifera) usage in Australian horticulture. This blow fly species lays eggs onto carrion soon after death and the resultant larvae that hatch are necrophagous and feed on the decomposing tissues of the dead animal. Newly hatched larvae of this fly were provided with plant-based meals (soya bean and canola) and compared with animal-derived meatmeal to determine if plant-based meal could be used to mass rear this blow fly species. Both soyabean and canola meal media did not support the survival of any larvae through to adult eclosion. The addition of only 10% whole egg powder to the plant-based meals enabled survival to eclosion of 39% and 13% on soyabean and canola based medias respectively compared with 76% on animal-based meatmeal with 10% whole egg powder. Larvae fed livestock meatmeal with 10% whole dried egg powder had the fastest development to the pupal stage, the highest pupation rate, the heaviest pupae and the highest subsequent adult eclosion. This study concluded that the use of plant-based meals in the mass rearing of the blow fly C. vicina was neither viable, nor economically viable.

Introduction: Despite its high prevalence and impact on health, metabolic dysfunction-associated steatotic liver disease (MASLD) is inadequately addressed in European primary care (PC), with a large proportion of cases going undiagnosed or diagnosed too late. A multi-country European re-search consortium led a project to design and evaluate a patient-centered, integrated model for MASLD screening, diagnosis and linkage to specialty care for European PC settings. Aim: Based on the lessons from this project, the latest research evidence and existing guidelines for the management of MASLD, we sought to develop a set of practice recommendations for screening, referral and management of MASLD in PC. Methods: The Rand/UCLA modified Delphi panel method, with two rounds, was used to reach consensus on practice recommendations. The international panel consisted of experts from six countries, representing family medicine, gastroenterology, hepatology, cardiology and public health. Initially, fifteen statements were drafted based on a synthesis of evidence from the literature and earlier findings from our consortium. Prior to the consensus meeting, the statements were rated by the experts in a first round. Then, in a hybrid meeting, the experts discussed findings of round one, adjusted the statements and reassessed the updated recommendations in a second round. Results: In round one, there was already a high level of consensus on 10 out of 15 statements. After round 2, there were fourteen statements with a high agreement (>90%). One statement was not endorsed. The approved recommendations addressed the following practice areas: risk screening and diagnosis, management of MASLD – Lifestyle interventions, pharmacological treatment of MASLD/MASH, pharmacological treatment for co-morbidity, integrated care, surgical management and other referrals to specialists. Conclusion: The final set of 14 recommendations focuses on increasing comprehensive care for MASLD in PC. The recommendations provide practical evidence-based guidance tailored to PC practitioners. We expect that these recommendations will contribute to the ongoing discussion on systematic approaches to tackle MASLD and support European PC providers by integrating the latest evidence into practice.

Precision medicine (PM), also termed stratified, individualised, targeted or personalised medicine, embraces a rapidly expanding area of research, knowledge, and practice. It brings together two emerging health technologies to deliver better individualised care: the many “-omics” arising from increased capacity to understand the human genome; and “big data” and data analytics including Artificial Intelligence (AI). PM has the potential to transform an individual’s health, moving from population-based disease prevention to more personalised management. There is however a tension between the two, with a real risk that this will exacerbate health inequalities and divert funds and attention from basic healthcare requirements leading to worse health outcomes for many. All areas of medicine should consider how this will affect their practice, with PM now strongly encouraged and supported by government initiatives and research funding. In this review we discuss examples of PM in current practice and its emerging applications in primary care, such as clinical prediction tools that incorporate genomic markers and pharmacogenomic testing. We look towards potential future applications and consider some key questions for PM including evidence of real-world impact, its affordability, the risk of exacerbating health inequalities, and the computational and storage challenges of applying PM technologies at scale.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p < 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

The platelet count, a component of the full blood count, has been identified as a useful diagnostic marker for cancer in primary care. The reference range for the platelet count is 150 to 400 or 450 × 109/l; this range does not account for natural variation in platelet count by age and sex. This study used three primary care cohorts from England Canada, and Australia. Patients aged 40 years and over with a full blood count were included and stratified by age (in 10-year bands), sex, (male/female), and platelet count group. Cancer incidence within one year of test date was estimated from linked registry data. In all three countries there was a clear upwards trend in cancer incidence with increasing platelet count, for both sexes and at all age groups. Lung and colorectal were the most common sites. These results have important implications for the international application of this work; analysis of local health datasets will be crucial to determine appropriate thresholds. Appropriate upper thresholds will depend on local populations, healthcare needs, and priorities. Further research is needed to assess the likely impact of new recommendations on the healthcare system, on cancer outcomes, and patient benefit.

Anxiety disorders, characterized by excessive fear and anxiety, are increasingly recognized as significant comorbidities in chronic diseases such as Chronic Obstructive Pulmonary Disease (COPD). This study aimed to evaluate the prevalence of anxiety in COPD patients referred from primary care centers to pulmonology services and identify predictive factors for anxiety. Conducted as a multicentric, observational, and prospective study, 293 COPD patients were recruited, undergoing comprehensive respiratory and smoking histories, spirometry, and anxiety assessments using the Hospital Anxiety and Depression Scale (HADS). These results show: a diagnosis of suspected anxiety in in 85 patients (29.0%): 17 possible and 68 with a strong suspicion. The study found significant associations between anxiety and factors such as gender (women showed a risk 3.5 times higher than men), weight, and body mass index (BMI). Disease severity, smoking status, and clinical manifestations did not significantly influence anxiety prevalence. The findings underscore the need for systematic psychological evaluations in COPD management, advocating for the use of simple diagnostic tools like the HADS to facilitate referrals to mental health services. Addressing anxiety in COPD patients could potentially improve their quality of life and disease outcomes. The study highlights the importance of a multidisciplinary approach involving family medicine, pulmonology, and psychiatry to optimize COPD patient care and suggests future research should focus on the impact of anxiety treatment on COPD progression. These insights call for integrating psychological assessments into routine clinical practice for comprehensive COPD management.

Cytologic diagnosis of extra‐adrenal paraganglioma presenting as a peripancreatic mass is challenging with a high rate of diagnostic error. We present a case of a peripancreatic mass identified by radiology as a gastrointestinal stromal tumor. Endoscopic ultrasound‐guided fine needle aspiration (FNA) of the mass showed a moderately cellular tumor composed of small to medium sized neoplastic cells with round to oval nuclei arranged singly and in loose clusters. The cells were positive for neuroendocrine markers (synaptophysin and chromogranin) and negative for CD117. A diagnosis of a neoplasm with a neuroendocrine tumor (NET) was made on FNA cytology. The subsequent surgical resection of the tumor revealed peripancreatic paraganglioma with immunohistochemistry positive for synaptophysin, chromogranin, and S100. The latter delineates the sustentacular cells. Although paraganglioma is a well recognized tumor, a detailed comparison of peripancreatic paraganglioma versus pancreatic/gastrointestinal NET is still lacking.

Research is scarce regarding antimicrobial use and antimicrobial resistance (AMR) for specific localities in Northern Ireland (NI). Additionally, the effects of COVID-19 on antimicrobial pre-scribing patterns and AMR are unknown. Between the European Union (EU) and United States (US), AMR causes approximately 68,000 deaths annually. This study will provide a better understanding of antimicrobial use and prescribing patterns in Belfast and link with AMR. An electronic survey was developed and distributed to eighty-five community pharmacists in Belfast. Yearly and monthly prescription data was gathered from the Business Services Organisation and COVID-19 statistics from Gov.uk. All data was analysed on Microsoft Office Excel® and IBM® SPSS® Statistics 25. Overall response rate was 46%. Most pharmacists (82%) failed to address prescriber non-compliance with guidelines and antimicrobial dosing errors (59%). The most common in-dication for antibiotics was upper respiratory tract infections (URTIs). Overprescribing of anti-biotics was perceived as the leading cause of AMR, therefore 69% of pharmacists indicated in-creased General Practitioner (GP) compliance with guidelines would reduce AMR. Pharmacists’ are in an ideal position to reduce AMR through patient education however, it is demonstrated that pharmacists failed to adequately counsel patients on antibiotic use. All GP practices demonstrated inappropriate antibiotic use, especially for URTIs which suggests antibiotic appropriateness should be reviewed. Many patients avoided contact with GP’s during COVID-19 which may have resulted in reduced antibiotic use. This research established amoxicillin as the most commonly prescribed antibiotic, which is contributing to increased AMR with its broad-spectrum activity and has recognised a decrease in antibiotic prescribing during COVID-19. Based on the results found and a critical review of the literature it is recommended antimicrobial guidelines should be re-viewed and improved, enhanced training should be provided to pharmacists and the antibiotic guardian (AG) campaign should be reenergised.

Background: Escalating climate change concerns have prompted the healthcare sector, particularly anaesthesia, to reassess its practices to align with environmental sustainability. Anesthetic gases like desflurane, sevoflurane, and isoflurane significantly impact the environment due to their high Global Warming Potentials (GWPs) and prolonged atmospheric lifetimes. This manuscript investigates these impacts and advocates for strategies to reduce the carbon footprint of anesthetic care while maintaining patient safety. Methods: We reviewed the environmental impacts of anesthetic gases and explored various strategies for sustainable anaesthesia. These strategies include adopting anesthetics with lower GWPs, enhancing recycling and waste reduction techniques, transitioning to intravenous anaesthesia, and implementing low-flow anaesthesia methods. We also examined barriers to these strategies, such as educational gaps, technological challenges, resistance to change, and policy limitations. Results: Adopting anesthetics with lower GWPs, such as sevoflurane over desflurane, and implementing low-flow anaesthesia can significantly reduce greenhouse gas emissions. Recycling and waste reduction techniques, though challenging, offer additional environmental benefits. Transitioning to intravenous anaesthesia can eliminate the direct GWP contributions from volatile anesthetic gases. However, these strategies require comprehensive education, advocacy for research and innovation, strategic change management, and supportive policies. Conclusions: Continuous monitoring and evaluation are crucial to ensure the effectiveness of sustainable practices in anaesthesia. Establishing robust Key Performance Indicators (KPIs) and utilizing advanced analytical tools will enable the anaesthesia community to adapt and refine practices. Collaborative efforts among clinicians, policymakers, and stakeholders are essential to significantly reduce the environmental impact of anaesthesia and promote ecological responsibility within healthcare.

The supply of mental health processes in primary care has gaps. This study aims to analyze the association of agreement criteria and flows between primary care teams and the Family Health Support Center (NASF) for mental health collaborative care, considering the difference between capital and non-capital cities in Brazil. This cross-sectional study was conducted based on secondary data from the Primary Care Access and Quality Improvement Program. Agreement criteria and flows were obtained from 3883 NASF teams of the matrix support or collaborative care. The Chi-square test and multiple Poisson regression were used; p < 0.05 was considered statistically significant. Prevalence ratios of negative associations demonstrated protective factors for support actions: follow-up at Psychosocial Care Center, management of psychopharmacotherapy, offer of other therapeutic actions, care process for users of psychoactive substances, and offer of activities to prevent the use of psychoactive substances. Collaborative care in primary care was effective, and capital cities were a protective factor compared with non-capital cities.

Noninvasive brain stimulation technique can be used for modulation of motor behaviors such as reaction time (RT). The main aim of this study was to investigate whether RT during a sequential visual isometric pinch task (SVIPT) can be affected by anodal transcranial direct current stimulation (a-tDCS) over three different stimulation sites such as dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1) or posterior parietal cortex (PPC). We also aimed to assess if stimulation of these cortical sites affect the transfer of learning during SVIPT. A total of 48 right-handed healthy participants were randomly assigned to one of the four a-tDCS groups: 1) left M1, 2) left DLPFC, 3) left PPC and 4) sham. A-tDCS was applied concurrent with SVIPT in which the participants were precisely controlled their forces to reach seven different target forces from 10 to 40% of maximum voluntary contraction (MVC) presenting on a computer screen with right dominant hand. Four test blocks were randomly performed at baseline and 15 min after the intervention including sequence and random blocks with either hand. Our results showed significant differences between a-tDCS groups on ratio RT in the sequence blocks of both the right trained (P = .041) and left untrained hands (P = .023) for target forces of 15% and 30 % of MVC, respectively. In sequence blocks, M1 showed significant elongation in ratio RT for the target force of 15% and 30 % MVC compared to PPC and Sham groups in the right hand. In sequence blocks with left hand, this negative effect were found between M1-DLPFC and M1-Sham groups. In random blocks, no significant differences were found among four groups at each target forces for the left hand while there were significant differences for 15% (P =. 04) and 40% MVC (P =. 035) in the right hand. Our findings suggest that three different stimulation sites (DLPFC, M1 or PPC) were differentially affected by a single session of a-tDCS at some target forces during SVIPT. The effects of a-tDCS on ratio RT were transferred in the left untrained hand for sequence blocks but not random blocks. Further research is needed to understand fundamental aspects of these main areas of the brain on temporal processing in a precision control task such as SVIPT.

Background: We assessed the pertinence of yearly updating the International Working Group on the Diabetic Foot (IWGDF) risk classification in people with diabetes by quantifying the changes in the risk group and its accuracy in identifying those developing an ulcer (DFU) in a primary care setting. Methods: In our retrospective cohort study, we included all people with diabetes with a foot as-sessment registry between January 2016 and December 2018 in the Baixo Alentejo Local Health Unit. Foot-related data was collected at baseline after one and two years. DFU and/or death until December 2019 were registered. The proportion of people changing their risk status each year was calculated. Accuracy measures of the IWGDF classification to predict DFU occurrence at one, two, and three years were calculated. Results: A total of 2097 people were followed for three years, during which 0.1% died, and 12.4% developed a DFU. After two years, 3.6% of the participants had progressed to a higher-risk group. The IWGDF classification presented specificity values superior to 90% and negative predictive values superior to 99%. Conclusion: Foot risk status can be safely updated every two years instead of yearly. The IWGDF classification can accurately identify those not at risk of DFU.

The process of international migration causes a situation of vulnerability in people's health and greater difficulty in coping with disease. Furthermore, the adversities suffered during migration can trigger reactive signs of stress and cause anxious, depressive, confusional and somatic symptoms. This article studies the relationships between psychosocial risk, psychological distress and somatization in immigrants from 4 communities: Maghrebis, Sub-Saharans, South Americans and South Asian. A cross-sectional study was carried out with questionnaires on 602 immigrants who were surveyed in the Primary Care Centres of an urban area of Catalonia. The instruments used were the Demographic Psychosocial Inventory (DPSI), the Brief Symptom Inventory (BSI) and the Somatic Symptom Inventory (SSI). The average psychosocial risk obtained was 0.35, with the highest values in the sub-Saharan community. Psychological distress showed a mean value of 0.66, with the sub-Saharan community scoring the lowest in all dimensions except depression. The average somatization values were 1.65, with the sub-Saharan community scoring the least. The female gender is a risk factor for somatization and psychological distress. Perceived psychosocial risk is a predictor of psychological distress, but not somatization, suggesting that the use of more adaptive coping strategies could minimize the effect of the migration process on somatizations.

Mediterranean Diet (MD), rich in minimally processed plant foods and in monounsaturated fats, but low in saturated fats, meat and dairy products, represents one of the most studied diets for cardiovascular health. It has been shown, from both observational and randomized controlled trials, that MD reduces body weight, improves cardiovascular disease surrogates such as waist-to-hip ratio, lipids, and inflammation markers, and even prevents the development of fatal and non-fatal cardiovascular disease, diabetes, obesity, and other diseases. However, it is unclear whether it offers cardiovascular benefits from its individual components or as a whole. Furthermore, limitations in the methodology of studies and meta-analyses have raised some concerns on its potential cardiovascular benefits. MD is also associated with characteristic changes in the intestinal microbiota, mediated through its constituents. These include increased growth of species producing short-chain fatty acids, such as Clostridium leptum and Eubacterium rectale, increased growth of Bifidobacteria, Bacteroides and Faecalibacterium prausnitzii species, and reduced growth of Firmicutes and Blautia species. Such changes are known to be favorably associated with inflammation, oxidative status, and overall metabolic health. This review will focus on the effects of MD on cardiovascular health through its action on gut microbioma.

Introduction: Atrial fibrillation (AF) is a common cardiac arrhythmia whose prevalence rises with age and is linked to increased morbidity and mortality due to the risk of thromboembolism. Management typically involves anticoagulation and rhythm control, but the treatment of elderly patients with multiple comorbidities requires careful consideration of drug side effects and interactions. Cibenzoline, a Vaughan-Williams class IA antiarrhythmic, is effective against AF but has risks of toxicity, especially in older people and those with renal impairment, due to its renal excretion and prolonged half-life in these populations. Discussion: This paper presents a case of an 80-year-old woman with paroxysmal AF who suffered cardiac arrest due to cibenzoline toxicity despite receiving standard adjusted dosages. The patient's cibenzoline blood concentration was significantly higher than the therapeutic range, leading to cardiotoxicity, which was exacerbated by drug interactions with bisoprolol and edoxaban, both metabolized by the CYP3A4 enzyme. Venoarterial extracorporeal membrane oxygenation (V-A ECMO) and intra-aortic balloon pump (IABP) successfully managed the cardiac arrest. This case emphasizes the unpredictable pharmacokinetics of cibenzoline in elderly patients with renal impairment and the need for vigilant therapeutic drug monitoring to avoid adverse events. Conclusions: Cibenzoline can pose a significant risk of severe toxicity in elderly patients with renal impairment, and drug interactions may potentiate this risk. The paper underscores the importance of careful dose adjustment and monitoring of drug levels in this population. In cases of cibenzoline-induced cardiac arrest, V-A ECMO and IABP are effective treatment modalities. The case study serves as a critical reminder for clinicians to remain vigilant for drug-induced complications and to apply aggressive supportive treatments when necessary.

Abstract Objectives: The aim of this study is to understand the rationale for the lack of interest to perform regular opportunistic oral cancer screening (OCS) by primary care providers (PCPs) and the challenges they have in incorporating OCS into their annual examination protocol. Method: Sequential exploratory mixed methods were used. Both qualitative and quantitative data from PCPs working at Nebraska Medicine were obtained. One-on-one in-depth interviews were performed to identify PCP's perceptions and challenges in performing OCS. The themes identified in the qualitative study were used as a guide in the development of survey questionnaires. The survey was emailed to all the PCPs (N=100), whose information was available on the Nebraska Medicine publicly accessible website. Results: The response rate was 34%. Approximately 60% of the participants mentioned that they currently perform oral cancer screening, but only 3.8% of the providers answered that they were performing comprehensive oral cancer screening every time. Forty-eight percent of the providers identified time as the biggest challenge. Over 35.3% of the providers answered that they perform screenings for patients with a history of tobacco (i.e., smoking) or alcohol use. Conclusion: Around half of the participants identified lack of time as their primary challenge in performing OCS and lack of knowledge as their second main obstacle. Very few provided comprehensive OCS and visual examination of the oral cavity is the only step performed often. Keywords: Oral cancer screening - Primary care providers - Oropharyngeal cancer-early detection of cancer-cancer screening-care providers-Health care professionals, health care providers

Improving the quality and access to healthcare services in rural areas is fundamental to develop sustainable healthcare systems. This research aims to explore the motivations of healthcare professionals to work and settle in rural island areas of Greece with limited access to secondary and tertiary care. The study suggests practical ways to encourage self-motivation and attract more health workers in rural areas. An exploratory qualitative research approach was employed, involving semi-structured interviews with 16 healthcare professionals working in primary care units that lack direct hospital or hospital-health center access. The research was conducted specifically in the rural islands of Cyclades. Thematic analysis was conducted to identify common themes and unique insights from the participants. The analysis revealed three thematic categories. Τhe «attraction» thematic was influenced by personal factors, random selection, origin, accommodation factors, professional factors and obligatoriness. The «recruitment» thematic was associated with understaffing, special care issues, unstable working environment, educational and organizational aspects, and insular lifestyle. The thematic of «retention» highlighted personal issues, accommodation difficulties, economic and work-related issues, and unique challenges posed by an insular lifestyle. This research provides valuable insights into the motivations that drive healthcare professionals to settle, work, and remain in remote island units, as well as the challenges they encounter in making this decision. The study proposes strategies to motivate and attract more healthcare professionals to rural areas. These findings should be considered when formulating or reviewing primary healthcare empowerment policies to ensure equitable healthcare access for all individuals.

Background: The study investigates patients' use of eHealth services, awareness of the availability of these services, and their intention to use them in primary care. It also examines patient characteristics and factors that influence their use. Methods: A cross-sectional design using questionnaire were conducted. Based on the unified theory of acceptance and use of technology (UTAUT), participants rated the two most common services. Descriptive analyses and linear correlation analyses were performed. Simple linear regression was conducted identify factors influencing participants' intention to use eHealth services. Results: 1203 participants were surveyed and their’ ages averaged 43.7 years. Participants usage rates varied, with the lowest at 2.4% for measuring vital signs and the highest at 47.4% for booking appointments. Intentions to use services ranged from 22.5% for video consultations to 46.6% for prescription refill requests. Approximately 20% of respondents were unaware of each service's availability. Positive associations were found between all constructs and the intention to use online services, with younger age being the most significant factor. Conclusions: Use of and intentions to use eHealth services varied greatly. Participants were often unaware of the availability of services. Promoting the availability and benefits of eHealth services could enhance patient engagement in primary care settings.

(1) Background: Cardiorespiratory fitness (CRF) is a prognostic factor regarding long time morbidity and mortality. To assess CRF the well-known gold standard is cardiopulmonary exercise testing (CPET), which is a time consuming and expensive test. Therefore, alternative methods for routine evaluation of CRF are needed for the general population as well as for specific patient groups such as children and young adults with congenital heart disease. The Stair Climbing Test (SCT) is a simple and resource saving test reported in the current literature. This test is used in various settings to assess different health associated risk factors including cardiorespiratory fitness, muscular resilience, therapy effectiveness or pre- and postoperative morbidity and mortality.

Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare and inherited vascular disorder, characterized by the development of arteriovenous malformations (AVMs) in various organs and telangiectasia (small AVM) in the mucocutaneous. The majority of HHT patients have haploinsufficiency of genes involved in the transforming growth factor-beta (TGFβ) signaling pathway, including endoglin (ENG), activin receptor-like kinase 1 (ALK1, also known as ACVRL1), or SMAD4. Active angiogenesis is also required for telangiectasia and AVM development. Anti-angiogenic strategies have been tested in patients and animal models extensively. However, the exact mechanisms for telangiectasia and AVM development remain unclear. In this review, we discuss recent advances in identifying disease mechanisms, and potential therapeutic targets.

Fever control is essential in patients with severe traumatic brain injury (TBI). The efficacy of therapeutic hypothermia (TH) in severe TBI has been investigated over the last few decades; however, in contrast to experimental studies showing benefits, no evidence of efficacy has been demonstrated in clinical practice. In this review, the mechanisms and history of hypothermia were briefly outlined, while the results of major randomized controlled trials (RCTs) and meta-analyses investigating TH for adult TBI are introduced and discussed. The retrieved meta-analyses showed conflicting results, with a limited number of studies indicating benefits of TH. Some studies have shown benefits of long-term TH compared with short-term TH. Although TH is effective at lowering elevated intracranial pressure (ICP), reduced ICP does not lead to favorable outcomes. Low-quality RCTs overestimated the benefits of TH, while high-quality RCTs showed no difference or worse outcomes with TH. RCTs assessing standardized TH quality demonstrated the benefits of TH. As TBI has heterogeneous and complicated pathologies, applying a uniform treatment may not be ideal. A meta-analysis of young patients who underwent early cooling and hematoma removal showed better TH results. TH should not be abandoned, and its optimal should be advocated on an individual basis.

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.

The nematode Caenorhabditis elegans, with its highly sensitive olfactory system, has emerged as a promising tool for testing chemotaxis. In the field of cancer diagnostics, there is a growing interest in the development of non-invasive screening methods for the detection of volatile organic compounds in a patient's urine. The objective of this study was to contribute to the existing body of knowledge by evaluating the ability of a Caenorhabditis elegans-based chemotaxis assay to discriminate between urine samples from healthy individuals and patients diagnosed with breast or colon cancer. Following synchronization of the developmental stages of C. elegans, nematodes were exposed to the urine of cancer patients and healthy individuals. Subsequently, chemotactic indices were calculated for each urine sample. Our results demonstrated a statistically significant difference in the chemotactic response of C. elegans to urine samples from cancer patients compared to healthy volunteers (p < 0.001). Moreover, the test exhibited promising diagnostic utility, with a sensitivity of 98%, a specificity of 62%, and a detection rate of 78%. Our findings expand on previous observations, confirming the remarkable sensitivity of C. elegans hermaphrodites to discriminating cancer-related volatile organic compounds in urine samples.

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase- (PI3K-) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K- remain unclear. We hypothesized MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K- pathway. Five days after receiving a single bolus of 0.075 units bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-1, oxidative loads, Masson’s trichrome staining, extracellular collagen levels, positive staining of -smooth muscle actin, PI3K- expression, and myonuclear apoptosis (P &lt; 0.05). Decreased diaphragm contractility and peroxisome proliferator activated receptor- coactivator-1 levels were also observed (P &lt; 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K- activity (P &lt; 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated through PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

Multi-cancer early detection (MCED) tests are being developed, but little is known about patient receptivity to their use for cancer screening. The current study assessed patient interest in such testing. Our team conducted a prospective, observational study among primary care patients in a large, urban health system. They were asked to complete a telephone survey that briefly described a new blood test in development to identify multiple types of cancer, but was not currently recommended or covered by insurance. The survey included items to assess respondent background characteristics, perceptions about MCED testing, and interest in having such an MCED test. We also used multivariable analyses to identify factors associated with patient interest in test use. In 2023, we surveyed 159 (32%) of 500 identified patients. Among respondents, 125 (79%) reported a high level of interest in having an MCED test. Interest was not associated with personal background characteristics, but was positively associated with the following expectations: testing would be recommended for cancer screening, be convenient, and be effective in finding early-stage disease (OR=11.70, 95% CI: 4.02, 34.04, p < 0.001). Research is needed to assess patient interest and actual uptake when detailed information on testing is presented in routine care.

Laryngopharyngeal reflux (LPR) is a prevalent disease in the general population and may have acute or chronic clinical presentation. LPR may be misdiagnosed in primary care medicine regarding the lack of gastroesophageal reflux disease symptoms and the lack of findings at the gastrointestinal endoscopy. Depending on the physician field of expertise and experience, LPR may be clinically over- or under-diagnosed. The management of LPR is possible in primary care medicine but primary care physician has to consider some red flags that requires to address the patient to otolaryngologist or gastroenterologist. The use of patient-reported outcome questionnaire such as reflux symptom score-12 and the consideration of some oral and pharyngeal findings visualized through the mouth opening may help the primary care physician to evaluate the LPR findings at the diagnosis time and throughout treatment. In this review, we provide a practical algorithm of management of LPR for primary care physician or other specialists that cannot perform fiberoptic examination. In this algorithm, physician has to exclude some confounding conditions such as allergy or other causes of pharyngolaryngitis and red flags. Physician may prescribe an empirical treatment based on diet and behavioral changes with or without medication, depending on the complaint severity of the patient. In case of prescription of medication, proton pump inhibitors and alginate have to be considered in association to protect the upper aerodigestive tract mucosa from acid, weakly acid and alkaline pharyngeal reflux events.

Background: Current management of COPD is predominantly focused on respiratory aspects. A multidimensional assessment including nutritional assessment, quality of life and disability provides a more reliable perspective of the true complexity of COPD patients. Methods: Prospective observational study of 120 elderly COPD patients at high risk of acute exacerbations. The Mini-Nutritional Assessment (MNA) was administered in addition to the usual respiratory assessment. The primary outcome was a composite of moderate or severe acute exacerbations during 52 weeks of follow-up. Results: The median MNA Short Form (SF) score was 11 (8-12), 39 participants (32.50%) had normal nutritional status, 57 (47.5%) were at risk of malnutrition and 24 (20%) were malnourished. Our multivariate linear logistic models showed that the MNA score was associated with dyspnea and respiratory symptoms severity assessed by the Modified British Medical Research Council (mMRC) and the COPD Assessment Test (CAT) score, with spirometric variables, in particular with the severity of airflow limitation based on the value of FEV1 and with poorer QoL as assessed by the EQ-5D-3 questionnaire. Cox regression analysis according to nutritional status based on the MNA score showed that COPD participants "at risk of malnutrition" and "malnourished" had a higher risk of moderate to severe acute exacerbations with a hazard ratio (HR) of 3.54 (p=0.002) and 8.20 (p=0.0001), respectively. Conclusion: Our study confirms the importance of assessing nutritional status in elderly COPD patients and its prognostic value.

Multidrug resistant organisms (MDROs) outbreaks have been steadilyincreasing in Intensive care units (ICUs). Still, healthcare institutions and workers (HCW) reached no unanimity on how and when implementing infection prevention and control (IPC) strategies. We aimed to provide a pragmatic, physician practice-oriented, resume of strategies towards different MRDOs outbreaks in ICU. We performed a narrative review on IPC in ICUs, investigating patient-to-staff ratios, education, isolation, decolonization, screening and hygiene practices, outbreak reporting, cost-effectiveness, reproduction-number(R0), and future perspectives. The most effective IPC strategy remains unknown. Most studies focus on a specific pathogen or disease, making the clinician losing the big picture. IPC strategies proved their cost-effectiveness regardless typology, country, or pathogen. A standardized, universal, pragmatic protocol for HCW education should be elaborated. Likewise, a rapid outbreak recognition tool elaboration (i.e., an easy-to-use mathematical model) would improve early diagnosis and spreading prevention. Further studies are needed to express in favor or against MDROs decolonization. New promising strategies are emerging and need to be tested in the field. The lack of IPC strategies application has made, and still makes ICUs a major MDROs reservoir into the community. In a not-too-distant future genetic engineering and phage therapies could represent a plot-twist in MDROs IPC strategies.

In the context of evolving perceptions of sexuality, particularly within the realm of health and disability, this study investigates the impact of multiple sclerosis (MS) on female sexual function and quality of life. A quantitative study involving 130 female MS patients aged 35 to 50 was conducted, employing measures such as The Female Sexual Function Index (FSFI), The Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19), and The Fatigue Severity Scale (FSS). Results indicate a significant association between greater sexual dysfunction and poorer quality of sex life, alongside the correlation of increased fatigue with diminished sexual satisfaction. Factors such as education level, time of diagnosis, and treatment regimen also influenced outcomes. Findings underscore the importance of supportive interventions, including counseling, to enhance the quality of sex life for women with disabilities, particularly those with MS.

Background: There is a lack of knowledge about how nurses and general practitioners (GPs) collaborated during the COVID-19 pandemicin primary care settings. Our study examined the roles of primary care nurses during the pandemic’s first wave, between March and June 2020, in Switzerland. Methods: The study involved all eight general practices implementing of a nursing role to the practice’s team. Primary care practice staff members (nurses, GPs and medical assistants) have been involved on the development of a new organizational model. A mixed-methods design study collected quantitative data using daily activity monitoring and an electronic survey. Additionally, eight nurses and nine GPs participated in a focus group discussion and individual interviews. Results: GPs recognized the substantial contributions, versatility, and autonomy of the primary care nurses in their practices during the pandemic. Those nurses experienced their involvement positively, mainly thanks to their perceived autonomy. The distribution of activities between primary care practice professionals was heterogenous due to extrinsic and intrinsic factors. Conclusion: Both nurses and GPs agreed that there was added value in having primary care nurses ingeneral practices in time of crisis, and this agreement will bolster plans to integrate this workforce across the canton. The development of nurses’ roles in primary care during the pandemic was reliant on many factors, including practice organization and Switzerland’s healthcare reimbursement and payment system

Artificial intelligence (AI) has grown in healthcare in recent years. The UK government recognises AI’s potential to enhance NHS services, yet research on AI in primary care (PC) has received limited attention. AI acceptance presents unique challenges in PC, characterised by fragmented structures, heterogeneous data sources, and multiple government departments. The organisational levels within PC are categorised as macro, meso, and micro levels. Existing research has predominantly focused on micro-level stakeholders. Our online survey addressed this research gap by encom-passing stakeholder perspectives at all levels. The results demonstrate the critical role of me-so-level stakeholders in facilitating AI acceptance. Importantly, a lack of understanding of AI terminology and concepts, concerns over potential job displacement, and the importance of em-pathy in patient care are highlighted as key challenges. Stakeholders also express the need for standardised AI terminology, comprehensive training, and regulatory standards to ensure equi-table and effective AI utilisation. This study lays the foundation for future in-depth interviews and further exploration of AI's role in PC. Observations in secondary care indicate that practitioners have substantial concerns about AI, how it works, and its limitations. Explainable AI can help technologists address such concerns, but first, we need to understand primary care's information needs.

The concept of vulnerable carotid plaques is pivotal in understanding the pathophysiology of is-chemic stroke secondary to large-artery atherosclerosis. At the macroscopic evaluation, vulnera-ble plaques are characterized by one or more of the following features: microcalcification, neo-vascularization, lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), thin fibrous caps, plaque surface ulceration, huge dimension determining stenosis, and plaque rupture. Recognizing these macroscopic characteristics is crucial to estimating the risk of cerebrovascular events, also in case of non-significant (less than 50%) stenosis. Inflammatory biomarkers, such as cytokines and adhesion molecules, lipid-related markers like oxidized low-density lipoprotein (LDL), and proteolytic enzymes capable of degrading extracellular matrix components are among the key molecules that will be scrutinized for their associative roles in plaque instability. Through their quantification and evaluation, these biomarkers reveal intricate molecular cross-talking govern-ing plaque inflammation, rupture potential, and thrombogenicity. Current evidence demonstrates that plaque vulnerability phenotypes are multiple and heterogeneous and are associated with as many highly complex molecular pathways that determine the activation of an immune-mediated cascade that culminates in thromboinflammation. This narrative review provides a comprehen-sive analysis of current knowledge on molecular biomarkers expressed by symptomatic carotid plaques. It explores the association of these biomarkers with the structural and compositional at-tributes that characterize vulnerable plaques

If we assume that: a. The four fundamental forces of nature are independent waves without rest masses, and their speeds are constant in a vacuum, just like light. b. Light or electromagnetic waves and gravity are comparable in structures. Weak and strong interactions are similar in structures. c. Light and weak interaction have the same speed c_L with spin number +1 or –1. d. Gravity and strong interaction have the same speed c_G without spin. e. The primary particles, namely electrons, electron neutrinos, and dark neutrinos in this paper, are made by the above four waves. We can find and describe some fundamental characteristics of the primary particles (e.g., their sizes, energies, and interactions) and introduce new attractive results from them (e.g., the source of the Pauli exclusion principle, the solution to the Einstein-Podolsky-Rosen paradox, and c_G slightly faster than c_L).

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

Abstract: Background and objective: Iliopsoas abscess (IPA) is a rare condition with varied symptomology and etiology. Less than one-third of patients with IPA present on the emergency department (ED) admission with the traditional triad of fever, back pain, and restricted hip motion (or limp), leading to delays in diagnosis and management. This case report aims to bring awareness among healthcare professionals regarding the atypical presentation and introduce a potential differential diagnosis when evaluating patients with fever and back pain. The intention is to provide insights into the signs and symptoms that may indicate the presence of an iliopsoas abscess and prompt additional investigations. Case report: Here, we describe a case of primary iliopsoas abscess associated with drug-induced acute liver failure in our ED. The patient complained of pain in the left lumbar region and fatigue that started two weeks before this presentation, claiming that, during the previous night, the pain suddenly worsened. She had a fever, pain at palpation in the right hypochondriac and left lumbar regions, accompanied by fever and vomiting, jaundiced skin, and sclera at the examination in ED. On abdominal ultrasonography, the diagnosis of acute cholangitis was suspected. The laboratory test shows leukocytosis with neutrophilia, thrombocytosis, hepatocytolysis syndrome, and hyperbilirubinemia with the predominance of indirect bilirubin. We performed then abdominal and pelvic computed tomography, which confirmed the diagnosis of cholelithiasis observed with the diameter of the bile duct within normal limits but also showed an abscess-like collection fused to the interfibrillar level of the left iliopsoas muscle; a diagnosis we most likely would have been missed. After that, the patient was hospitalized in the General Surgery Department, and surgery drainage of the abscess was performed. The patient's evolution was excellent; she was discharged after 11 days. Conclusions: The case presented here exemplifies how iliopsoas abscess, a rare cause of back pain, can quickly go unrecognized, especially in the emergency department. Our experiences will raise awareness among doctors in emergency departments about this uncommon but essential diagnosis. With advancements in diagnostic tools and techniques, we aspire that more cases of iliopsoas abscess will be accurately diagnosed.

The aim of this study was to compare the effect of using L-PRF in patients undergoing impacted lower third molar surgery with either primary or secondary closure techniques. Methods: This prospective, randomised, double-blind, split-mouth clinical trial was conducted in patients with bilateral lower impacted third molars of similar position. Primary closure was performed in group 1 and secondary closure in group 2. Group 1 closure technique was applied to one side of the patients and group 2 closure technique was applied to the other side at different times. Nine pa-tients were excluded from the study due to alveolitis and failure to attend regular control visits out of the 45 patients evaluated. Results: Of the 36 patients included in the study, 23 were female and 13 were male and the mean age was 22.42±3.36 years. The secondary closure group had lower VAS scores at hour 6 (p

Traumatic Brain Injury (TBI) is one of the leading causes of death and disability worldwide. Patient treatment and management pose a challenge for healthcare systems. The prognosis of these patients may be influenced by factors such as sex. This study aims to describe the clinical parameters of patients hospitalized in the Intensive Care Unit (ICU) of a Spanish hospital due to Trauma Brain Injury and to establish differences based on sex. Methodology: An observational, cross-sectional, and analytical study was conducted from March 2015 to December 2019. All patients admitted to the ICU during this period who presented isolated significant Traumatic Brain Injury, defined as an abbreviated injury scale (AIS) ≥ 3, were included. Data on baseline characteristics, mechanism of injury, substance use, and acute management in the prehospital and hospital stages (including the need for hospitalization) were recorded. A descriptive and in-ferential analysis was conducted using the chi-square test. Results: A total of 950 patients were ultimately included. The majority of the patients were men (723) with a mean age of 45.16 (± 17.55). There were statistically significant differences in terms of the mechanism of injury (p

Keywords: Oral health, diabetes, periodontal disease, caries, periodontitis.

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive in-crease in mean pulmonary arterial pressure. Mutations in the BMPR2 and AQP1 genes have been described in familial PAH. The bone morphogenetic proteins BMP9 and BMP10 bind with high affinity to BMPR2. Administration of BMP9 has been proposed as a potential therapeutic strategy against PAH, although recent conflicting evidence dispute the effect of such practice. Considering the involvement of the above molecules in PAH onset, progression, and therapeutic value, we ex-amined the effects of modulation of BMP9, BMPR2, and AQP1 on BMP9, BMP10, BMPR2, AQP1, and TGFB1 expression in human pulmonary microvascular endothelial cells in vitro. Our results demonstrated that silencing the BMPR2 gene resulted in increased expression of its two main ligands, namely BMP9 and BMP10. Exogenous administration of BMP9 caused return of BMP10 to basal levels, while restored the decreased AQP1 protein levels and the decreased TGFB1 mRNA and protein expression levels caused by BMPR2 silencing. Moreover, AQP1 gene silencing also resulted in increased expression of BMP9 and BMP10. Our results might possibly imply that the effect of exogenously administered BMP9 on molecules participating in the BMP-signaling pathway could depend on the expression levels of BMPR2. Taken together, these results may pro-vide insight into the highly complex interactions of the BMP-signaling pathway.

Frequent and excessive consumption of alcohol, be it episodic or sustained misuse, ranks among the top causes of mortality globally. This comprehensive analysis seeks to elucidate how alcohol misuse precipitates death, with a particular focus on associated cardiac anomalies. Notably, the phenomenon of "Holiday Heart Syndrome," linked to binge drinking, is recognized for inducing potentially fatal cardiac arrhythmias. Moreover, persistent alcohol consumption is implicated in the development of alcoholic cardiomyopathy, a condition that underlies heart failure and arrhythmic disturbances of the heart. Additionally, individuals undergoing withdrawal from alcohol frequently exhibit disruptions in normal heart rhythm, posing a risk of death. This review further delves into additional alcohol-related mortality factors, including the heightened likelihood of hypertension, cerebrovascular accidents (strokes), and the connection between excessive alcohol use and Takotsubo syndrome.

The presence of anti SARS-CoV2-RBD antibody (Anti-RBD) prevents severe COVID-19. We aimed to determine the accuracy of a point-of-care Anti-RBD test implemented in person living with HIV (PLWH), systemic lupus erythematosus (SLE), and chronic kidney disease (CKD). We enrolled 182 non-comorbid subjects and 335 persons with comorbid (PLWH, SLE, CKD) to test anti-RBD assay compared to surrogate viral neutralization (SVNT) as the reference test. We performed linear correlation analysis between anti-RBD vs SVNT and a ROC analyses to ascertain anti-RBD cut-off at 30%, 60%, and 90% inhibition of SVNT to calculate accuracy. Correlations of anti-RBD to SVNT among all groups were excellent with R= 0.7903, R=0.7843, R=0.8153 among non-comorbid, SLE and CKD groups, respectively, with significantly higher correlation among the PLWH group (R=0.8877; p-value=0.0072) compared to non-comorbid group. The accuracy of the anti-RBD test among PLWH and CKD group was similar with the non-comorbid but showed lower sensitivity in the SLE group (p=0.000014). The specificity of the test remained high in all groups. In conclusion, the Anti-RBD test had excellent correlation to SVNT. The persistently high specificity in all groups suggests that this test can be reliably utilized to detect presence of low neutralization capacity, prompting additional vaccination.

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

The early 2-factor (E2F) family of transcription factors, including E2F1-8, plays a critical role in apoptosis, metabolism, proliferation, and angiogenesis within glioblastoma (GBM). However, the specific functions of E2F transcription factors (E2Fs) and their impact on the malignancy of Bevacizumab (BVZ)-responsive GBM subtypes remain unclear. This study used data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to explore the impact of eight E2F family members on the clinical characteristics of BVZ-responsive GBM subtypes and possible mechanisms of recurrence after BVZ treatment.To predict the possibility of GBM patient survival and progression, we classified and comparedthe expression of E2Fs according to BVZ-responsive subtypes and employed a machine learning method-TreeBagger, one random forest algorithm. Multiple bioinformatics analyses have shown that the significant increased E2F8 post BVZ treatment may enhance the function of angiogenesis and stem cell proliferation, indicating one of the mechanisms of GBM recurrence after treatment. In addition, BVZ treatment in unresponsive GBM patients may potentially worsen disease progression. Our findings suggest that E2F family members play important roles in GBM malignancy and BVZ treatment response, highlighting their potential as prognostic biomarkers and therapeutic targets and recommending precise BVZ treatment for GBM patients.

International migrants comprised 14% of the UK population in 2020, but migrant health in the UK has rarely been studied at a population level using primary care electronic health records (EHRs). Given the difficulty of determining migration status using EHRs, this study developed a migration phenotype and assessed its validity. We developed a phenotyping algorithm using codes for country of birth, visa status, non-English main/first language and non-UK origin. It was applied to a Clinical Practice Research Datalink (CPRD) GOLD database of 16,071,111 primary care patients between 1997 and 2018. We compared the completeness and representativeness of the identified migrant population to Office for National Statistics (ONS) country of birth and 2011 census data by year, age, sex, geographic region of birth and ethnicity. Between 1997-2018, 403,768 migrants (2.51% of the CPRD GOLD population) were identified using the phenotype. 178,749 (1.11%) of these migrants were identified by codes indicating foreign country of birth or visa status, 216,731 (1.35%) a non-English main/first language, and 8,288 (0.05%) non-UK origin. The cohort was similarly distributed compared to ONS migration statistics in terms of sex and region of birth. Recording of migration improved from identifying approximately one-tenth of the expected proportion of migrants according to the ONS in 2004 to a quarter in 2018. Younger migrants were better represented than those aged 50 and over. The migration phenotype identified a large number of migrants and can be used to undertake large-scale migration health research in CPRD GOLD to inform healthcare policy, practice and action. While the cohort was representative of the UK migrant population in terms of sex and region of birth, migration status was under-recorded in earlier years and older ages, and future studies for these groups should therefore be interpreted with caution.

Objective: To verify knowledge about HPV, promote educational action and encourage vaccination among students from 6th to 9th grade in the public school system of Campo Grande - MS. Methods: Conducting a structured interview. Results: It was pointed out that 70.1% had heard about HPV, however, 38.1% stated that it is a virus that causes cancer and 11.3% related it to the virus that causes warts. The free availability of the vaccine was known to 57.7% of participants and 62.3% were vaccinated with at least one dose. 79 students were vaccinated during the actions. Conclusion: There is a lack of knowledge, as the majority did not know how to relate HPV to the development of cervical cancer. The interaction between primary health care and schools resulted in the dissemination of knowledge about HPV, an increase in vaccine doses administered, favoring an increase in vaccination coverage among students.

Aim: The aim of this study is to evaluate the possibility of discriminating between the two sexes through the simultaneous use of cheiloscopy and palatine rugoscopy. Materials and methods: 80 palate and lip impressions (40 male and 40 female) were analyzed. The palate impressions were acquired using both analogue and digital methods. The lip impres-sions were first acquired analogically and then scanned. The morphology of the palatine rugae in the palate impressions was analyzed, with the exclusion of segmental rugae. The lip prints were analyzed in sextants and the morphology of the lip wrinkles was evaluated. Results: Palatine rugoscopy shows that women have more curvy rugae than men and that men have more rugae on the left side than on the right. Cheiloscopy gave no statistically significant re-sults. Discussion: Palatine rugoscopy showed some differences between the sexes, however, these re-sults were not solid enough for reliable sex discrimination. Differences between the results of dif-ferent studies can be attributed to ethnic and methodological variations. Cheiloscopy, on the other hand, did not provide statistically significant results for sex discrimination. Conclusions: Given the scant results obtained from palatine rugoscopy and the lack of statisti-cally relevant results in cheiloscopy, together with a lack of concordance among the data found in literature, it is believed that it is not possible to discriminate between the two sexes by using the two methods contemporarily. Further research is needed.

Several studies have shown that antibiotics, analgesic – sedative, and antiseizure medications are among the most commonly used medications in preterm and sick neonates. These infants are at high risk of developing nosocomial infections, central nervous system complications, and are exposed to numerous painful/stressful procedures. These severe, potentially life-threatening complications may have serious short- and long-term consequences and should be prevented and/or promptly treated. Previous studies and reviews have revealed significant variability in medications used in neonatal intensive care units (NICUs) worldwide, especially concerning the indications and dosages of first-line medications. This variability indicates the lack of adequate studies regarding the effectiveness and safety of these medications in neonates, especially the preterm ones. Important obstacles contributing to inadequate studies in preterm infants include difficulties in obtaining parental consent, physicians’ unwillingness to recruit preterm infants, the lack of license for use in neonates, and other scientific and ethical concerns. This review is an update on the use of antimicrobials – antifungals, analgesics – sedatives, and antiseizure medications used in neonates, focusing on existing evidence or knowledge gaps regarding their pharmacokinetics, indications, safety, dosage regimen (dose, dosing interval, route of administration), and evidence-based guidelines for the optimal use in neonates.

Introduction Emergency laparotomy is a surgical procedure associated with significantly higher mortality rates compared to elective surgeries. Awake laparotomy under neuraxial anaesthesia has recently emerged as a promising approach in abdominal surgery to improve patient outcomes. This study aims to evaluate the feasibility and potential benefits of using lumbar spinal anaesthesia as the primary anaesthetic technique in emergency laparotomies. Methods We conducted a case series involving 16 patients who underwent emergency laparotomy for bowel ischemia, perforation, or occlusion. Lumbar spinal anaesthesia was employed as the main anaes-thetic technique. We analysed patient demographics, clinical characteristics, intraoperative details, and postoperative outcomes. The primary outcome measures included the adequacy of postoper-ative pain control, the incidence of postoperative complications, and mortality rates. Results Among the 16 patients, adequate postoperative pain control was achieved, with only 2 patients requiring additional analgesia. Postoperative complications, including sepsis, wound dehiscence, and pneumonia, were observed in 7 patients (44%). The observed mortality rate was relatively low at 6% (1 patient). Notably, conversion to general anaesthesia was not necessary in any of the cases, and no early readmissions were reported. Discussion Our findings highlight the feasibility and potential benefits of using neuraxial anaesthesia in emergency laparotomies. The observed low mortality rate and the avoidance of conversion to general anaesthesia suggest that lumbar spinal anaesthesia may be a useful alternative in emer-gency settings. However, the occurrence of postoperative complications in 44% of patients indi-cates the need for cautious patient selection and close monitoring. Further research with larger sample sizes is warranted to fully elucidate the efficacy, safety, and potential impact of this tech-nique on patient outcomes in emergency laparotomies.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) has proven to be effective in reducing the rate of recurrence and disease as secondary prevention (evidence-based intervention) in patients who have suffered from myocardial infarction (MI). CR is a multidisciplinary path in which the patient is followed pharmacologically, from a psychological, nutritional, nursing and physiotherapy point of view. Post-MI patients present a reduction in the performance of the diaphragm muscle, the main inspiratory muscle, and this condition can become a risk factor for further relapses or for the onset of heart failure. Despite the solidity of the international guidelines for CR, the latter are lacking in specifically indicating an evaluation and training path regarding the inspiratory muscles in post-MI patients who have not undergone cardiac surgery. The article reviews the information on the adaptation of the diaphragm post-MI and highlights the need for clearer indications for a rehabilitation process that gives importance to the diaphragm.

Abstract: Endoglin (ENG) is a causative gene of type 1 hereditary hemorrhagic telangiectasia (HHT1). HHT1 patients have arteriovenous malformations (AVMs) in multiple organs, including the brain. In mice, Eng deletion induced by R26RCreER or SM22aCre leads to AVM development in the brain and other organs. We have reported that the severity of brain AVM in mice with activin receptor-like kinase 1 (Alk1, an HHT2 causative gene) mutation is correlated with the number of Alk1 negative endothelial cells (ECs). We hypothesized that increase of Eng negative ECs will enhance AVM severity. To increase EC Eng deletion, we used a codon improved cre (icre), which is more potent in recombination of floxed alleles than the wild type (WT) cre. R26RCreER;Eng^f/f mice that have Rosa promoter driving and tamoxifen (TM) inducible WT cre expression globally and PdgfbiCreER;Eng^f/f that have Pdgfb promoter driving and TM inducible icre expression in ECs were treated with 3 intra-peritoneal injections of TM (2.5 mg/25g of body weight) to delete Eng globally or in the ECs. AAV-VEGF was stereotactically injected into the brain to induce brain focal angiogenesis and brain AVM. We found that iCre caused more Eng deletion in the brain indicated by lower level of Eng proteins (p<0.001) and fewer Eng positive ECs (p=0.01) than mice with WT cre. Mice with iCre mediated Eng deletion have more abnormal vessels (p=0.02), CD68⁺ macrophages (p=0.002), and hemorrhage (p=0.04), and less vascular pericyte and smooth muscle coverage than mice with WT cre. In addition, arteriovenous shunts were detected in the intestines of icre mice, a phenotype that have not been detected in WT cre mice before. RNAseq analysis showed that 8 out of the 10 top upregulated pathways identified by Gene Ontology (GO) analysis are related to the inflammation. Therefore, increase of Eng deletion in ECs exacerbates AVM severity, which is associated with enhanced inflammation. Strategies that can reduce Eng negative ECs could be used to develop new therapies to reduce AVM severity for HHT1 patients.

This article presents a new input device for spastic patients and others with similar symptoms. The sensor consists of a disc used to determine positions and can replace standard joysticks in medical devices such as electric-powered wheelchairs. Using a standard joystick while operating a powered wheelchair can result in dangerous situations when spastic movements occur and extremities cramp making them uncontrollable. To avoid this, a disc was developed that can be controlled with any body part. By shifting weight (x- and y-axis) the disc can tilt in any direction creating a proportional output signal and can also be pushed down in the center (z-axis) to open a menu on a screen for example. When spasms occur it is impossible for users to get stuck on the input device because the disc is flat and can be mounted within a control panel. Body parts coming into contact with the disc would merely slide across the disc without triggering unintentional actions. The sensor presented here is also adaptive and can be adjusted to fit a user’s strength and range of motion. This proposal aims to develop an input device that enables spastic patients to operate sensitive systems safely.

Anxiety in older individuals is understudied despite its prevalence. Investigating its occurrence can be challenging, yet understanding the factors influencing its recurrence is important for improved management. This study aimed to model the recurrence of anxiety symptomatology in an older population within a five-month timeframe. Data included baseline socio-demographic and general health information for older adults aged 60 years or older with at least mild depressive symptoms. A Bayesian network model explored the relationship between baseline data and recurrent anxiety symptomatology. Model evaluation employed the Area Under the Receiver Operating Characteristic Curve (AUC). The Bayesian model was also compared to three machine learning models. The model achieved an AUC of 0.821 on the test data, using a threshold of 0.367. This result surpassed both the Logistic Regression and XGBoost models, but slightly behind SGDClassifier. Key factors associated with recurrence of anxiety symptomatology were: “Not being able to stop or control worrying”; “Becoming easily annoyed or irritable”; “Trouble relaxing”; and “depressive symptomatology severity”. The model demonstrated generalisation abilities and outperformed some machine learning models while being less complex and more explainable. These findings indicate a prioritised sequence of predictors to identify individuals most likely to experience recurrent anxiety symptomatology.

Heart failure (HF) affects about 60 million people worldwide, making it one of the chronic conditions with the greatest health and economic impact. The primary objective was to assess the efficacy of lung ultrasound (LUS) in the management of HF in order to intervene early and reduce the rate of hospital readmissions. A systematic search was conducted on PubMed, Embase, Google Scholar, Web of Science, and Scopus, including clinical trials, meta-analysis, systematic reviews, and original articles from 2019/1/1-2023/12/31, about LUS for the assessment of HF, on an outpatient basis, for HF diagnosis or/and decompensation. There may be risk of bias because the effects are dependent on the persons delivering the intervention. The results were synthetized by PRISMA method. A total of 873 articles were identified of which 33 articles were selected: [n=19] focused on prognostic assessment of HF, [n=11] centred on multimodal diagnostic assessments, and [n=2] addressing therapeutic guidance for HF diagnosis. LUS exhibits advantages in the detection of sub-clinical congestion linked to prognostic significance in re-admission and mortality during out-patient follow-up, after hospital discharge, and in complex scenarios as the patients' homes or institutional long-term care facilities. However, there are considerable uncertainties in their interpretation and monitoring changes due to its lack of standardization. The need for an updated international consensus on the use of LUS seems obvious.

Background: Misconceptions and knowledge gaps about antibiotic use contribute to inappropriate antibiotic use and antimicrobial resistance. Aim: Identifying and prioritizing misconceptions and knowledge gaps about antibiotic use from a healthcare professionals’ perspective. Methods: A modified Delphi study of two rounds with an expert meeting. A literature search was conducted to create statements about misconceptions and knowledge gaps about antibiotic use. These were rated by healthcare professionals from five EU countries representing general practice, out-of-hour services, nursing homes, and pharmacies. Consensus was achieved if ≥80% of the participants rated 4+ on a five-point Likert scale during the second Delphi round. Results. In total, 44 misconceptions were identified through the literature search within four themes: 1) antimicrobial resistance in general, 2) use of antibiotics in general, 3) use of antibiotics for respiratory tract infections, and 4) use of antibiotics for urinary tract infections. Consensus was reached for more than half of the statements within each setting. Conclusions. Experts from different settings and nationalities acknowledge that multiple misconceptions and knowledge gaps can contribute to inappropriate use of antibiotics in the community. These results provide valuable information to use in educational campaigns for patients and healthcare professionals to improve the use of antibiotics.

Despite Vitamin B12's recognized importance for the nervous system, there's still a lack of research on the association between Vitamin B12 and sleep, especially in primary care settings. We assessed Vitamin B12 levels in adult primary health care users and investigated correlations with sleep quality, insomnia and sleepiness. In this cross-sectional study, 512 consecutive participants were included. Information regarding anthropometrics, socio-demographics, and medical history was obtained. The Epworth Sleepiness Scale (ESS), Athens Insomnia Scale (AIS), and Pittsburg Sleep Quality Index (PSQI) were used to quantify excessive daytime sleepiness (EDS), insomnia symptoms, and sleep quality, respectively. Median Vitamin B12 was 342 (266, 446) pg/mL. After adjustments, Vitamin B12 levels&lt;342 pg/mL showed significant associations with insomnia symptoms [OR (95% CI) 2.434 (1.331–4.452), p=0.004], especially in elderly, non-obese and female participants, with EDS only in obese participants [OR (95% CI) 3.996, (1.006-15.876), p=0.039]. Nonetheless, there was no significant association between B12 levels and poor sleep quality (OR 1.416, 95% CI 0.678-2.958, p=0.354). In conclusion, our results show that lower Vitamin B12 was associated with insomnia symptoms and sleepiness in specific groups of participants. However, further research with objective measurements of sleep is crucial to assess the relationship between sleep and Vitamin B12.

Objectives: Female genital mutilation (FGM) is a significant public health problem. It is estimated around 14,700 women affected by FGM live in Switzerland, primarily among women with a history of migration. Our qualitative research investigated the sexual health of immigrant women living with FGM in Switzerland, describing their own perception of health, reproductive life and sexuality. Methods: We conducted semi-structured, in-depth interviews with a group of eight immigrant women of African origin living in Switzerland with Type III FGM (infibulation). Results: Seven of the women were from Somalia and one from Ivory Coast. All of the Somali women were mothers and married (two separated), and the Ivorian woman was a single mother. The women in our study reported a low level of sexual satisfaction and reproductive health. They affirmed their desire to improve, or at least change, their condition. Although they rarely talk with their husbands about sexual subject matter, they would like to include them more and improve dialogue. Conclusions: Specific socio-sexual management is recommended when caring for immigrant women living with FGM in order to respond to their specific health care needs. Multidisciplinary approaches may be able to offer more comprehensive health care, including facilitated communication to improve dialogue between women and health care professionals, and eventually between women and their husbands in discussing sexual matter.

PURPOSE: To investigate the oxylipin profiles in aqueous humor of primary open angle glaucoma (POAG) patients. METHODS: Aqueous humor samples were collected from 17 POAG patients and 15 cataract subjects and subjected to the liquid chromatography-mass spectrometry (LC-MS) analysis to detect the oxylipins. The prediction potential of the differential abundant oxylipins was assessed by the receiver operating characteristic (ROC) curves. Pathway and correlation analyses on the oxylipins and clinical and biochemical parameters were also conducted. RESULTS: The LC-MS analysis detected a total of 76 oxylipins, of which 29 oxylipins reached the detection limit. The multivariate analysis identified 5 differential abundant oxylipins, 15-keto-prostaglandin F2 alpha (15-kPGF2α), Leukotriene B4 (LTB4), 12,13-Epoxyoctadecenoic acid (12,13-Epome), 15-Hydroxyeicosatetraenoic acid (15-HETE) and 11-Hydroxyeicosatetraenoic acid (11-HETE). The 5 oxylipins are enriched in the arachidonic acid metabolism and linoleic acid metabolism pathways. Pearson correlation analysis showed that 11-HETE was positively correlated with intraocular pressure and central corneal thickness and negatively with cup/disk ratio in the POAG patients. In addition, 15-kPGF2α was positively correlated with visual field defect, and LTB4 was negatively correlated with macular thickness.  CONCLUSIONS: This study revealed the oxylipin profile in the aqueous humor of POAG patients. Oxylipins involved in arachidonic acid metabolism pathway could play a role in POAG and anti-inflammatory therapies could be potential treatment strategies for POAG.

The late diagnosis of Type 2 Diabetes Mellitus can occur due to lack of access to the primary health care system and the non-manifestation of symptoms. Faced with this problem, this work presents the creation of a mobile application, called DiabetesCheck, for predicting the risk of Type 2 Diabetes Mellitus. A mathematical model is used, which classifies the risk of Type 2 Diabetes Mellitus for a group of patients with intervention and for a comparative group, using Fuzzy Classification and Decision Trees. The proposed application allows the health professional to monitor patients through the history stored in a database, allowing a representation of the evolution of patients and indication of medications. Therefore, this proposal aims to carry out the diagnosis in the initial phase of the disease and help in the prescription of more effective treatments and in the proposition of public policy strategies in epidemiology and screening.

Interprofessional collaboration between general practitioners (GPs) and community pharmacists (CPs) is central to implement antimicrobial stewardship (AMS) programs in primary care. This study aimed to design a GP-pharmacist antimicrobial stewardship (GPPAS) model in Australian primary care. A seven-component exploratory study was conducted since 2017 to 2021 to inform a GPPAS model. We generated both secondary and primary evidence through a systematic review, a scoping review, a rapid review, nationwide surveys of Australian GPs and CPs including qualitative components and a pilot study of a GPPAS model. All study evidence was synthesised, reviewed, merged and triangulated to design a prototype GPPAS model using a Systems Engineering Initiative for Patient Safety theoretical framework. Secondary evidence informed effective GPPAS interventions, and primary evidence captured interprofessional issues, challenges and future needs to implement GPPAS interventions by GPs and CPs. A GPPAS model framework involving GP-pharmacist team-based five GPPAS sub-models were successfully designed to foster AMS education, antimicrobial audits, diagnostic stewardship, delayed prescribing, and routine review of antimicrobial prescription by improved GP-CP collaboration. A GPPAS model could be used as a guide to collaboratively optimise antimicrobial use by GPs and CPs. Implementation studies on GPPAS model and sub-models are required to integrate GPPAS model into GP-pharmacist interprofessional care models in Australia.

Background: the primary care service in Catalonia has operated an asynchronous teleconsulting service between GPs and patients since 2015 (eConsulta), which has generated some 500,000 messages. New developments in big data analysis tools, particularly those involving natural language, can be used to accurately and systematically evaluate the impact of the service. Objective: the study was intended to examine the predictive potential of eConsulta messages through different combinations of vector representation of text and machine learning algorithms and to evaluate their performance. Methodology: 20 machine learning algorithms (based on 5 types of algorithms and 4 text representation techniques)were trained using a sample of 3,559 messages (169,102 words) corresponding to 2,268 teleconsultations (1.57 messages per teleconsultation) in order to predict the three variables of interest (avoiding the need for a face-to-face visit, increased demand and type of use of the teleconsultation). The performance of the various combinations was measured in terms of precision, sensitivity, F-value and the ROC curve. Results: the best-trained algorithms are generally effective, proving themselves to be more robust when approximating the two binary variables "avoiding the need of a face-to-face visit" and "increased demand" (precision = 0.98 and 0.97, respectively) rather than the variable "type of query"(precision = 0.48). Conclusion: to the best of our knowledge, this study is the first to investigate a machine learning strategy for text classification using primary care teleconsultation datasets. The study illustrates the possible capacities of text analysis using artificial intelligence. The development of a robust text classification tool could be feasible by validating it with more data, making it potentially more useful for decision support for health professionals.

Cellular senescence is the irreversible growth arrest subsequent to oncogenic mutations, DNA damage or metabolic insult. Senescence is associated with aging and chronic age associated diseases such as cardiovascular disease and diabetes. The involvement of cellular senescence in Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) is not fully understood however, recent studies suggest that such patients have a higher-than-normal level of cellular senescence and accelerated aging. This study aimed to discover key biomarkers of senescence in AKI and CKD patients compared to other chronic ageing diseases as controls. We show that senescence proteins CKAP4 and PTX3 are upregulated in AKI and CKD patients compared with controls with chronic diseases suggesting they may play in a role in overall kidney disease development. Additionally, CKAP4 was found to be differentially expressed in both AKI and CKD when compared to unhealthy controls hence this biomarker could be prognostic senescence biomarker of both AKI and CKD.

Background: The aim of this experimental work was to evaluate cheiloscopy potential: to confirm the individual uniqueness of lip prints, to verify the presence of recurrent patterns according to the Suzuki and Tsuchihashi classification and to search for characteristics that can be used in establishing the sex of a subject, with a focus on assessing the method's limitations. Methods: Lip prints were taken from a sample of 172 volunteers using liquid lipstick and transparent adhesive tape and were digitally analyzed. Results: 59 prints (35.3%) were not considered for Suzuki and Tsuchihashi classification due to quality errors and the impossibility of visualizing lip wrinkles in one or more sextants. All the digitized prints revealed themselves to be unique after having been analyzed using superimposition. Qualitatively valid prints indicated a prevalence of Type II in both male and female. A major problem was that the analysis of the same print by different operators often resulted in a different attribution of a Type. Conclusions: The potential of cheiloscopy lies mainly in the matching of prints, given their uniqueness, but the absence of a database greatly limits its use. Additionally, its use for sex identification does not seem to be reliable. It is necessary to establish an acquisition protocol for taking and analyzing prints that could reduce the errors committed by the operator.

Background: The aim of this experimental work was to confirm the individual uniqueness of lip prints, to verify the presence of recurrent patterns according to the Suzuki and Tsuchihashi classification and to search for characteristics that can be used in establishing the sex of a subject. Methods: Lip prints were taken from a sample of 172 volunteers using liquid lipstick and transparent adhesive tape and were digitally analyzed. Results: 59 prints (35.3%) were not considered for Suzuki and Tsuchihashi classification due to quality errors and the impossibility of visualizing lip wrinkles in one or more sextants, all the digitized prints revealed themselves to be unique after having been analyzed using superimposition. Qualitatively valid prints indicated a prevalence of Type II in both male and female and the presence of sex-linked features. A major problem was that the analysis of the same print by different operators often resulted in a different attribution of a Type. Conclusions: The potential of cheiloscopy lies mainly in the matching of prints, given their uniqueness, and can be a valid tool in gender determination but the absence of a database greatly limits its use. It is necessary to establish an acquisition protocol for taking and analyzing prints that could reduce the errors committed by the operator.

Abstract Introduction: Long COVID (LC) affects multiple systems and has a significant health impact on patients and society. Therefore, long COVID services should address patients’ needs through a holistic assessment and monitoring of patients’ symptoms. Aim: The aim was to understand which of the symptoms were most and least likely to improve, after our rehabilitation intervention so that the rehabilitation measures in the clinic could be modified to meet patients’ needs. At the same time, we wanted to assess the feasibility of using C19-YRS ELAROS application in monitoring of LC symptoms during and after the rehabilitation clinic attendance. Methodology: In this study, a total of 50 patients who have attended long COVID rehabilitation clinic in Salford, UK; were assessed by using digitalised C19-YRS ELAROS application. A total of 100 eligible initial and final post rehabilitation assessments were analysed. Conclusion: Pain and anxiety symptoms were the two most likely symptoms to improve after intervention at LC rehabilitation clinic, whereas swallowing difficulty is least likely to improve. Issues with caring for family/ social life (symptoms affecting social role) are likely to worsen even after treatment. It is feasible to monitor and track Long COVID symptoms utilising the digitalised version of C19-YRS via the ELAROS App. This also allows the tracking of symptoms overtime.

This mini-review explores the comparative efficacy, safety, and clinical outcomes of high-dose proton pump inhibitor (PPI) intravenous infusion versus oral acid pump inhibitor therapy following endoscopic treatment for bleeding peptic ulcers. Recent evidence suggests that intravenous PPIs can significantly reduce the rebleeding rates within the critical first 72 hours post-intervention, with a noted rebleeding rate of 6% compared to 14% in patients receiving oral Vonoprazan (VPZ) therapy. Additionally, the rapid onset of action associated with intravenous administration leads to faster stabilization of vital signs and a reduced need for subsequent blood transfusions. Safety profiles for both intravenous and oral VPZ were favourable, with minimal adverse effects, the most common being transient headaches.However, the findings from our single-centre study with a moderate sample size prompt consideration of more extensive, multicentre trials to enhance the generalizability of the results. Current limitations include potential biases, short-term focus, missing data issues, and a need for long-term outcome data, necessitating further research. Future studies should also explore the cost-effectiveness of intravenous versus oral VPZ and the impact on patient quality of life and long-term mortality rates.This review underscores the importance of tailored PPI therapy in managing bleeding peptic ulcers post-endoscopy. It suggests a potentially pivotal role for intravenous PPIs in high-risk patient groups, advocating for a shift towards more aggressive and immediate care protocols in specific clinical settings.

(1) Background Diabetic Retinopathy (DR) is the primary cause of poor vision in young adults. Screening for DR is important but many patients do not attend; (2) Methods: We validated an algorithm for predicting DR and its progression by conducting a retrospective study of 11 children in a population of 120,389 T2DM (3) Results: By applying the algorithm to the population showed an AUC of 0.93 (95% CI, 0.92–0.94) for any-DR and 0.90 (95% CI, 0.89–0.91) for referable-DR(4) Conclusions: The algorithm is useful for predicting patients who could develop referable forms of DR and also for any-DR. This would allow a personalized screening plan to be drawn up for each patient.

A diet with low content of fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) are established treatment for irritable bowel syndrome (IBS), with well-documented efficiency. A starch- and sucrose-reduced diet (SSRD) has shown similar promising effects. This randomized, non-inferiority study aimed to test SSRD against low FODMAP and compare the responder rates to a 4-week dietary intervention of either diet. 155 IBS patients were randomized to SSRD (n=77) or low FODMAP (n=78) for 4 weeks, with a follow-up 5 months later without food restrictions. The questionnaires Rome IV, IBS-severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS) were completed at baseline and after 2 and 4 weeks and 6 months. Weight, height, waist circumference, and blood pressures were measured. Comparisons were made within the groups and between changes in the two groups. There were no differences between groups at baseline. The responding rate (RR=∆Total IBS-SSS ≥−50) of SSRD was non-inferior compared with low FODMAPs at week 2 (79.2% vs. 73.1%;p=0.661;95% confidence interval (CI)=-20-7.2) and week 4 (79.2% vs. 78.2%;p=1.000;95%CI=-14-12), with borderline-significance at follow-up (36.4% vs. 42.3%;p=0.252;95%CI=-9.4-21). All gastrointestinal and extraintestinal symptoms were equally improved (p<0.001 in most variables). SSRD rendered greater reductions in weight (p=0.006), body mass index (BMI) (p=0.005), and sugar craving (p=0.05), whereas waist circumference and blood pressure were equally decreased. Weight and BMI were regained at follow-up. In the SSRD group, responders at 6 months still had lowered weight (-0.7 (-2.5-0.1) vs. 0.2 (-0.7-2.2) kg; p=0.005) and BMI (-0.25 (-0.85-0.03) vs. 0.07 (-0.35-0.77) kg/m²; p=0.009) compared with baseline in contrast to non-responders. Those who had tested both diets preferred SSRD (p=0.032). A 4-week SSRD intervention was non-inferior to low FODMAP regarding effects on gastrointestinal and extraintestinal IBS symptoms. Reductions of weight, BMI, and sugar craving were most pronounced following SSRD.

Background/Objectives: The purpose of this study was to evaluate the relationship between 1-year mortality and health insurance benefit extension policy items in severe pneumonia pa-tients requiring mechanical ventilation using a South Korean nationwide cohort. Methods: A nationwide population-based retrospective study was conducted using the Korean National Health Insurance database. A total of 1,099 patients (542 patients in the health insurance benefit item group and 557 patients in the control group) were included. The primary outcome was 1-year mortality. Results: Among patients with health insurance benefit extension policy items, 203 patients (37.5%) were diagnosed with hemato-oncological disease, who were categorized as group A, and 339 patients (62.5%) were diagnosed with cerebrovascular, cardiovascular, or rare diseases, who were categorized as group B. Group B had lower 1-year mortality (50.7% vs. 62.5%, P

Although it may seem paradoxical, primary care and mental health professionals develop prejudices and discriminatory attitudes towards people with mental health problems in a very similar way to the rest of the population. The main objective of this project was to design, implement and evaluate two awareness interventions respectively tailored to reduce stigma and discrimination beliefs and attitudes towards persons with a mental health diagnosis among primary care (PC) and mental health (MH) professionals. These interventions were developed by Obertament, the Catalan alliance against stigma and discrimination in mental health. The TLC3 (Targeted, Local, Credible, Continuous Contact) methodology was adapted to the Catalan PC and MH professional contexts. Activists with lived experience of mental health diagnosis carried out awareness-raising interventions in PC and MH health centres. The efficacy of these interventions was evaluated using two prospective double-blind cluster-wait-list-randomized-controlled trial experimental designs. Stigmatizing beliefs and behaviours were measured with the Opening Minds Stigma Scale for Health Care Providers in primary care centres and with the Beliefs and Attitudes towards Mental Health Service users’ rights in mental health centres. Positive reductions in both PC and MH professionals’ stigmatising beliefs and attitudes were found in the 1-month follow-up, although a ‘rebound effect’ at the 3-month follow up was also detected. This emphasizes the importance of the continuity of the presence of anti-stigma activities and messages. Attrition rates where high, which can hamper the reliability of the results. Further follow-up studies should enquiry effects of long-term interventions aimed at reducing stigmatising beliefs and attitudes among primary care and mental health professionals.

Background Healthcare workers (HCWs) have suffered considerable morbidity and mortality during the COVID-19 pandemic. Few data on COVID-19 vaccine effectiveness (VE) are available from middle-income countries in Europe. We evaluated primary series COVID-19 VE against laboratory-confirmed COVID-19 among HCWs in Georgia. Methods HCWs in six hospitals in Georgia were invited to enroll in a prospective cohort study conducted during March 19–December 5, 2021. Participants completed weekly symptom questionnaires. Symptomatic HCWs were tested by RT-PCR and/or rapid antigen test (RAT), and participants were routinely tested for SARS-CoV-2 by RT-PCR or RAT, regardless of symptoms. Serology was collected at enrolment, and quarterly thereafter, and tested by electrochemiluminescence immunoassay for SARS-CoV-2 antibodies. We defined primary series vaccination as two doses of COVID-19 vaccine received ≥14 days before symptom onset. We estimated VE as (1-hazard ratio)*100 using a Cox proportional hazards model with vaccination status as a time-varying covariate. Estimates were adjusted by potential confounders that changed the VE estimate by more than 5%, according to the change-in-estimate approach. Results Overall, 1561/3849 (41%) eligible HCWs enrolled and were included in the analysis. The median age was 40 (IQR: 30-53), 1318 (84%) were female, and 1003 (64%) had laboratory evidence of prior SARS-Cov-2 infection. At enrolment, 1300 (83%) were unvaccinated; By study end, 1082 (62%) had completed a primary vaccine series (69% BNT162b2 (Pfizer-BioNTech); 22% BBIBP-CorV (Sinopharm); 9% other). During the study period, 191(12%) participants had a new PCR- or RAT-confirmed symptomatic SARS-CoV-2 infection. VEa gainst PCR- or RAT- confirmed symptomatic SARS-CoV-2 infection was 58 (95%CI: 41; 70) for all primary series vaccinations, 68% (95%CI: 51; 79) for BNT162b2, and 40% (95%CI: 1; 64) for BBIBP-CorV vaccines. Among previously infected HCWs, VE was 58% (95%CI: 11; 80). VE against medically attended COVID-19 was 52% (95%CI: 28; 68), and VE against hospitalization was 69% (95% CI: 36; 85). During the period of predominant Delta variant circulation (July-December 2021), VE against symptomatic COVID-19 was 52% (95%CI: 30; 66). Conclusions Primary series vaccination with BNT162b2 and BBIBP-CorV was effective at preventing COVID-19 among HCWs, most of whom had previous infection, during a period of mainly Delta circulation. Our results support the utility of COVID-19 primary vaccine series, and the importance of increasing coverage, even among previously infected individuals.

Introduction: Drug interactions (DDIs) represent an important clinical problem particularly in elderly patients due to polytherapy, comorbidity and physiological change in pharmacodynamic and pharmacokinetic pathways. In this study we investigated the association between drugs prescribed during hospital or clinical room discharge and the development of DDIs with drugs daily used from each patient. Methods: we performed an observational, retrospective, multicenter study on medical records of outpatients referred to general practitioners. Drug interactions (DDIs) were measured using the drug interactions probability scale. Collected data were analyzed using the Statistical Package for the Social Sciences. Results: During the study we evaluated 1,622 medical records. We recorded the development of DDIs in 10.3% of patients, of those 11.6% induced the hospitalization. Logistic regression showed an association between DDIs and sex and number of drugs used (P = 0.023). Conclusion: this real-life study shows that DDIs are common in elderly patients and physicians must take more attention after hospital discharge revaluating the treatment in order to reduce the risk of DDIs and hospitalization.

Background: The importance of community health psychology in providing complex bio-psycho-social care is well-documented. We present a mixed-method study monitoring the efficacy of health psychology services in the Public Health Focused Model Program for Primary Care Development (2012-2017) in four disadvantaged micro-regions in North-East Hungary. Methods: Study 1 assessed the availability of the services using a sample of 17003 respondents. Study 2 applied a follow-up design to measure the efficacy of the health psychology services in a sample of 132 clients. In Study 3, we conducted focus group interviews to assess clients’ lived experiences. Results: More mental health issues and higher education predicted a higher probability of service use. Follow-up showed that individual and group-based psychological interventions resulted in lower depression and (marginally) higher well-being. Thematic analysis of the focus group interviews indicated that participants deemed topics like psychoeducation, a greater acceptance of psychological support, and heightened awareness of individual and community support important. Conclusions: The results of the monitoring studies demonstrate the important role health psychology services can play in primary health care in disadvantaged regions. Community health psychology can improve well-being, reduce inequality, support the population’s health awareness, and address unmet social needs in disadvantaged regions in Hungary.

The aim was to analyze the coping strategies used by primary health care (PHC) professionals. A cross-sectional, descriptive-analytical study was conducted with professionals working in primary health care units in São José do Rio Preto, a large city in the interior of São Paulo, Brazil. For data collection we used an instrument developed by the researchers, containing sociodemographic and professional variables, as well as the Problem Coping Modes Scale (EMEP). We evaluated 333 PHC professionals. A difference was observed between the scores of the four coping strategies (p<0.001), with the highest score for the problem-focused strategy (3.8) and the lowest score for the emotion-focused strategy (2.4). Physicians had the lowest scores in coping strategies focused on religious practices/fantastical thinking (p<0.001) and pursuit of social support (p=0.045), while community health agents had the highest scores in these coping strategies). Professionals working in PHC have different coping strategies for the problems and stressful situations experienced in the work environment. These strategies can involve more positive attitudes focused on confrontation and problem solving, to emotional responses that involve attitudes of avoidance and denial that involve attitudes of avoidance and denial of the problem.

.Bacground: Sepsis remains a major health challenge worldwide, characterized by a dysre-gulated host response to infection, leading to high mortality and morbidity in intensive care units (ICUs). The Fibrosis 4 (FIB-4) index, originally developed to assess liver fibrosis in hepatitis C patients, has recently been explored for its potential prognostic value in sepsis patients. Method: This study retrospectively analyzed 309 sepsis patients admitted to the Internal Me-dicine and Anaesthesia ICUs between December 12, 2021, and December 15, 2023, to inves-tigate the relationship between FIB-4 levels, Acute Physiology and Chronic Health Evaluation (APACHE), and Sequential Organ Failure Assessment (SOFA) and clinical outcomes. Results: The study found that higher FIB-4 measurements were statistically significantly asso-ciated with increased 28-day mortality, with a cut-off value of 4.9 providing a sensitivity of 54.92% and specificity of 74.25%. Logistic regression analysis indicated that elevated Conclusion:FIB-4 levels were a significant predictor of early mortality, suggesting that the FIB-4 index could serve as a valuable prognostic tool in assessing the severity and prognosis of sepsis patients.

: Suicide is a serious public health problem, with a global mortality rate of 1.4% of all deaths worldwide, and the leading cause of unnatural death in Spain. The use of clinical simulation has proven to be a beneficial tool in the training of nursing students. Such experiences allow them to develop cognitive and affective skills that are fundamental for the detection of warning signs and use of interventions in cases of people who want to take their own lives. Working in a mental health environment can be difficult for nursing students; therefore, the purpose of this study was to explore the perceptions of nursing students on the approach, management and intervention of suicidal crisis through clinical mental health simulation. Methods: qualitative descriptive phenomenological study through focus groups and reflective narratives in a sample of 45 students. A thematic analysis was performed using ATLAS-ti. Results: After the analysis, three themes were obtained: (a) management and handling of emotions (b) identification of suicide motives (c) intervention in suicidal crisis. Discussion: Clinical simulation in mental health allows students to exercise clinical judgment reasoning, detect warning signs for a better treatment approach, and provide tools for effective intervention and management of patient care. The results of this study indicate that nursing students face challenges in approaching mental health clinical simulation due to lack of prior exposure.

(1) Background: Several chronic respiratory diseases could be a risk factor for acquiring SARS-CoV-2 infection: among them, Primary Ciliary Dyskinesia (PCD) is a rare (about 1:10.000) inherited ciliopathy (MIM 242650) characterized by recurrent upper and lower respiratory tract infections due to a dysfunctioning of the respiratory cilia; We aimed to investigate if some polymorphisms of the TAS2R38 bitter taste receptor correlate with an increased prevalence of SARS-CoV-2 infection and severity of symptoms in a cohort of PCD subjects; (2) Methods: Patients answered several questions about possible SARS-CoV-2 infection, experienced symptoms and vaccinations; in case of infection, they also filled out a SNOT-22 and ARTIQ questionnaires; (3) Results: Forty PCD adult patients (mean age 36.6 ± 16.7 years, 23 females) participated to the study, out of which 30 % had tested positive for COVID-19 during the last four years; most of them reported a mildly symptomatic disease. We found no differences in age or sex, but a statistic significant difference (p=0.03) was observed in body mass index (BMI), that was higher in the COVID-acquired group (23.2 ± 3.3 vs 20.1 ± 4.1 kg/m2). Genotyping for TAS2R38 polymorphisms showed a prevalence of 28.6% PAV/PAV, 48.6% PAV/AVI and 22.8% AVI/AVI individuals in our cohort. In contrast to our hypothesis, we did not observe a protective role of PAV allele towards SARS-CoV-2 infection; (4) Conclusions: Our findings suggest that subjects with PCD may not be at increased risk of severe outcomes from COVID-19 and the TAS2R38 bitter taste receptor genotype type does not affect SARS-CoV-2 infection.

Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. Circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women and who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: 37 elderly women were separated into an elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using 1H-NMR and also insulin-dependent tissue specific glucose uptake in skeletal muscle were assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the 22:6 docosahexaenoic acid percentage of the total long chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (P = 0.015). DHA/FA associated significantly to skeletal muscle GU (P = 0.031) and M-value in the OLM group only (P = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and that this association is significantly weakened in the offspring of obese mothers.

Background: Chikungunya virus (CHIKV) diagnosis have become a challenge for primary care physicians in areas where zika virus and/or dengue virus are present. Case definitions for the three arboviral infections are overlapping. Methods: A cross-sectional analysis was carried out. A bivariate analysis was made using confirmed CHIKV infection as the outcome. Variables with significant statistical association were included in an agreement consensus. Agreed variables were analyzed in multiple regression model. The area under the receiver operating characteristic (ROC) curve was calculated to determine a cut-off value and performance. Results: 295 patients with confirmed CHIKV infection were included. A screening tool was made using symmetric arthritis (4 points), fatigue (3 points), rash (2 points) and ankle joint pain (1 point). The ROC curve identified a cut-off value and a score ≥ 5.5 was considered positive to identify CHIKV patients with a sensibility of 64.4% and a specificity of 87.4%, positive predictive value of 85.5%, negative predictive value of 67.7%, area under the curve of 0.72, and an accuracy of 75%. Conclusion: We developed a screening tool for CHIKV diagnosis using only clinical symptoms as well as proposed an algorithm to aid the primary care physician.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p&gt;0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

Invasive Candida infections represent a significant cause of morbidity and mortality in the neonatal intensive care unit (NICU), particularly among preterm and low birth weight neonates. The nonspecific clinical presentation of invasive candidiasis, resembling that of bacterial sepsis with multiorgan involvement, makes the diagnosis challenging. Given the atypical clinical presentation and the potential detrimental effects of delayed treatment, empirical treatment is often initiated in cases with high clinical suspicion. This underscores the need to develop alternative laboratory methods other than cultures, which are known to have low sensitivity and a prolonged detection time, to optimize therapeutic strategies. Serum biomarkers, including mannan antigen/anti-mannan antibody and 1,3-β-D-glucan (BDG), both components of the yeast cell wall, a nano-diagnostic method utilizing T2 magnetic resonance and Candida DNA detection by PCR-based techniques have been investigated as adjuncts to body fluid cultures and have shown promising results in improving diagnostic efficacy and shortening detection time in neonatal populations. This review aims to provide an overview of the diagnostic tools and the current management strategies for invasive candidiasis in neonates. Timely and accurate diagnosis followed by targeted antifungal treatment can significantly improve the survival and outcome of neonates affected by Candida species.

Autoimmune diseases of the liver and biliary tract require timely and accurate diagnosis. This study evaluates the D-tek panel (D-Tek, Mons, Belgium) of 10 immunodot antigens for its effectiveness in diagnosing autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). We retrospectively analysed serum samples from 111 patients who had undergone routine testing, including indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISA), to confirm or exclude autoimmune liver or biliary tract disease. The panel tested for M2/nPDC, M2/OGDC-E2, M2/BCOADC-E2, M2/PDC-E2, gp210, sp100, LKM1, LC1, SLA, and F-actin antigens. Results showed that all positive IIF+ELISA results were confirmed by the immunodot panel, except for two samples from patients never diagnosed with AIH. The immunodot test identified over 20 additional autoantibodies in samples initially negative by IIF, corroborated by laboratory imaging and medical history. The immunodot technique proved to be a quick, sensitive, and specific method with high overall accuracy. This study suggests that the immunodot technique may be an effective screening and confirmatory method for autoimmune liver diseases, potentially improving diagnostic efficiency and accuracy in clinical practice.

Primary percutaneous coronary intervention (pPCI) has revolutionized the prognosis of ST-segment ele-vation myocardial infarction (STEMI) and is the gold standard treatment. As a result of its success, the number of pPCI centres has expanded worldwide. Despite decades of advancements, clinical outcomes in STEMI patients have plateaued. Out-of-hospital car-diac arrest and cardiogenic shock remain a major cause of high in-hospital mortality, whilst the growing burden of heart failure in long-term STEMI survivors presents a growing problem. Many elements aiming to optimize STEMI treatment are still subject to debate or lack sufficient evidence. This review provides an overview of the most contentious current issues in pPCI in STEMI patients, with an emphasis on unresolved questions and persistent challenges.

Systemic hypertension has been recognized as a modifiable traditional cardiovascular risk factor and influenced by many factors such as eating habits, physical activity, diabetes and obesity. The objective of this study was to identify cardiometabolic factors that predict changes in blood pressure induced by a one-year lifestyle intervention in primary care settings involving a collaboration between family physicians, dietitians, and exercise specialists. Patients with metabolic syndrome diagnosis were recruited by family physicians participating in primary care lifestyle intervention among several family care clinics across Canada. Participants for whom all cardiometabolic data at the beginning (T0) and the end (T12) of the intervention were available were included in the present analysis (n=101). Patients visited the dietitian and the exercise specialist weekly for the first three months and monthly for the last nine months. Diet quality, exercise capacity, anthropometric indicators, and cardiometabolic variables were evaluated at T0 and at T12. The intervention induced a significant decrease in waist circumference (WC), systolic (SBP) and diastolic (DBP) blood pressure, and plasma triglycerides and an increase in cardiorespiratory fitness (estimated VO2max). Body weight (p<0.001), body mass index (BMI) (p<0.001), and plasma glucose (p=0.006) reduction and VO2max increase (p=0.048) were all related to changes in SBP. WC was the only variable for which changes were significantly correlated with those in both SBP (p<0.0001) and DBP (p=0.0004). Variations in DBP were not associated with changes in other cardiometabolic variables to a statistically significant extent. Twelve participants were identified as adverse responders in both SBP and DBP and displayed less favorable changes in WC. The beneficial effects of a lifestyle intervention on blood pressure were significantly associated with cardiometabolic variables, especially WC. These findings suggest that a structured lifestyle intervention in primary care can help improve cardiometabolic risk factors in patients with metabolic syndrome.

Non-toroidal shape primary pass through protection current transformers (CTs) are used to measure high currents. Their design provides them with a big airgap that allow passing several cables per phase though them, which is the main advantage versus toroidal types, as the number of CTs required to measure the whole phase current is drastically reduced. The cables pass through the transformer window can be in several positions. As the isolines of the magnetic field generated by the primary currents are centered in the cables, if these cables are not centered in the transformer window, the magnetic field will be non-uniform along the transformer core. Consequently, local saturations can appear if the cables are not properly disposed causing the malfunction of the CT. In this paper, the performance of a non-toroidal shape protection CT is studied. The research is focused on the cable position influence in possible partial saturations of the CT when it is operating near to its accuracy limit. Depending on the cable position, the ratio of the primary and secondary currents can depart from assigned ratio. The validation of this phenomenon has been carried out via Finite Element Analysis (FEA) showing that partial transformer core saturations appears in areas of the magnetic core close to the cable. Applying FEA, also the admissible accuracy region for cable positioning inside the CT is delimited. Finally, the simulation results are ratified with experimental tests performed in non-toroidal protection CTs varying the primary cables’ positions, which are subjected to currents up to 5 kA, achieving satisfactory results. From this analysis, installation recommendations are given.

Acute and chronic respiratory diseases impose a significant economic and health burden. Distal small airway assessment requires invasive procedures such as a bronchoscopy and bronchoalveolar lavage. The Particles in Exhaled Air (PExA) device provides a non-invasive means of assessing small airways; it captures distal airway particles sized around 0.5-7m and contains particles of respiratory tract lining fluid (RTLF) that originate during airway closure and opening. The PExA device can measure particle count and mass according to particle size. Subsequent capture of particles in a thin membrane enables application of various analytical methods to assess a broad range of biomolecules including phospholipids, proteins, inflammatory profile, and other metabolites to characterise inflammation and diseases processes such as asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, lung cancer, and more recently acute infections such as COVID-19. PExA analysis provides a promising alternative to traditional investigative methods in the assessment, diagnosis, and management of respiratory conditions. By evaluating specific biomarkers in the RTLF associated with airway inflammation, PExA may offer a more accurate and comprehensive understanding of the molecular-level changes in the small airways of patients with acute and chronic lung diseases.

Phyllanthus emblica (P. emblica) has been described in many studies to have multiple therapeutic activities and is considered an important part of Ayurvedic and Unani medicinal systems. This study successfully synthesized P. emblica loaded polyvinylalcohol/gelatin based cryogels (PVA/Gel/P.emblica) to examine their potential in wound dressing applications. Swelling tests, Brunauer-Emmett-Teller (BET) and morphology analysis were conducted within the scope of characterization studies. In vitro cell culture studies were performed using HaCaT cells to illustrate the suitability of the synthesized cryogels as wound dressing material. The swelling tests and BET analysis results showed that swelling and surface area properties of cryogels increased with increasing P. emblica amounts. Morphological results displayed that the cryogels had a dense, interconnected pore morphology and a macroporous structure. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), trypan blue exclusion and live-dead assay results revealed that adding of P. emblica into cryogels led to enhanced cell proliferation, increased cell number, and improved cell viability. Based on the phase contrast microscope, scanning electron microscope (SEM), immunofluorescence and giemsa staining images, it was observed that P. emblica promoted cell attachment, proliferation and penetration. In conclusion, it has been shown that PVA/Gel/P.emblica cryogels are suitable for use as wound dressing materials and can be developed with further studies.

Abstract: Laryngoscopy for tracheal intubation has been developed for many decades. Among various conventional laryngoscopes, videolaryngoscopes (VL) have been applied in different patient populations, including difficult airways. The safety and effectiveness of VL have been repeatedly studied in both normal and difficult airways. The superiority of VL then has been observed and is advocated as the standard of care. In contrast to laryngoscopy, the development of video-assisted intubating stylet (VS, also named as styletubation) has been noticed two dec-ades ago. Since then, sporadic clinical experiences of use have appeared in literature. In this re-view article, we presented our vast use experiences of the styletubation (more than 55,000 pa-tients since 2016). We found this technique is swift (the time to intubate: from 3 s to 10 s), smooth (first-attempt success rate: 100%), safe (no airway complications), and easy (high subjective satis-faction and fast learning curve for the novice trainees) in both normal and difficult airway sce-narios. We therefore propose styletubation technique can be feasibly applied as universal rou-tine use for tracheal intubation.

Our study aimed to identify predictors for the effectiveness of tumor regression in lung cancer patients undergoing neoadjuvant treatment and cancer resections. Patients admitted between 2016 and 2022 were included in the study. Based on the histology of the tumor, patients were categorized into lung adenocarcinoma group (LUAD), and squamous cell carcinoma group (SQCA). Ninety-five patients with non-small cell lung cancer were included in the study. Fifty-eight (61.1%) and 37 (38.9%) patients were included in the LUAD and SQCA groups, respectively. Nine (9.5%), 56 (58.9%), and 30 (31.6%) patients were categorized with a tumor regression score of I, II, and III respectively. In multivariable analyses, histology of the primary tumor (SQCA), lymph node size in the preoperative CT scan (>1.7cm) and absolute tumor size reduction after neoadjuvant treatment (>2.6 cm) independently predict effectiveness of tumor regression (OR, [95% Confidence interval, p-value] of 6.88 [2.40-19.77, p70 years, extended resection >one lobe, and tumor recurrence or metastasis were identified as significant independent predictors of reduced overall survival. Assessment of tumor size before and after neoadjuvant treatment might help to identify high-risk patients with decreased survival and to improve patient management and care.

The new NICE guideline for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), published in October 2021, makes significant changes in treatment recommendations. It acknowledges the complexity of this chronic medical condition, which always impacts quality of life and can be profoundly disabling, recognising the prejudice and stigma that people with ME/CFS often experience in the absence of any specific diagnostic test. The guideline outlines steps for accurate diagnosis, recognising post-exertional malaise as a core symptom; importantly, ME/CFS can now be diagnosed after just 3 months in a bid to improve long-term health outcomes. It recommends the need for individual, tailored management by a multi-disciplinary team, ensuring that the wellbeing of the individual is paramount. The guideline makes clear that any programme based on fixed incremental increases in physical activity or exercise, for example graded exercise therapy (GET), should not be offered as a treatment for ME/CFS and emphasises that cognitive behavioural therapy (CBT) should only be offered as a supportive intervention. Because of the rigorous methodology required by NICE Committee review and the inclusion of the testimony of people with lived experience as committee members, this guideline will influence the future diagnosis and management of ME/CFS in the UK and beyond.

Verticillium wilt is a soil borne disease caused by distinct vegetative compatibility groups (VCG) of the fungus Verticillium dahliae. Two V. dahliae isolates were recovered from symptomatic cot-ton plants in Australian cotton fields and were assigned to two distinct vegetative compatibility groups (VCGs). One corresponding to the defoliating (VCG 1A) and the other non-defoliating (VCG 2A) pathotypes of Verticillium, have been transformed with Red and Green Fluorescent protein genes, respectively. The transformants maintained their ability to infect cotton and both strains were observed to colonise the xylem vessels of cotton plants. Moreover, we observed that the cotton V. dahliae strains could also infect some sampled non-Gossypium species found in the Australian landscape. The fluorescently labelled strains of V. dahliae will allow us to gain a thorough understanding of the infection processes of this important pathogen.

Type 2 diabetes (T2D) is associated with increased cardiovascular morbidity, mortality, and hospital admissions. There is variability in clinical practice. The objectives are to analyze the variability in the control of Blood Pressure (BP), HbA1c, and LDL-C in T2D patients and its influence on admissions due to cardiovascular events (CVE) Methods: We analyzed the electronic records in Primary Care Health centers in Navarra (Spain) and hospital admission for CVE. We follow 480637 people from 2012 to 2016. We calculated indicators of control of patients with T2D for each year, percentage with: HbA1c &lt; 7%; HbA1c &gt;= 9%; BP &lt;140/90 mmHg; LDL-C &lt;100 mg/dl. We used logistic and Cox regression. Results: Patients in the best control GP practices cluster are 2.5 times more likely to have HbA1c &lt;7% [OR: 2.46 (95% CI: 2.29-3.64)]. Poor HbA1c control ≥ 9% is more likely in the worst control cluster [OR: 1.73 (95% CI:1.63-1.83)]. The probability of admission for CVE increases with age, being male, low income, obesity, history of CVE, having HbA1c ≥ 9%, and belonging to a GP practice in the cluster of HbA1C ≥ 9% worst control. In contrast, it decreases in patients with HbA1c &lt;7%, BP&lt;140/90 mmHg and LDL &lt;100 mg/dl.

Uveal melanoma (UM) poses a significant clinical challenge due to its high metastasis rate and poor prognosis. Melatonin, noted for its anti-cancer properties in various malignancies, including cutaneous melanoma, shows promise in UM treatment. This study aimed to evaluate melatonin receptor expression in primary UM and its association with UM-related mortality and prognostic factors. Immunohistochemical analysis of 47 primary UM tissues showed low expression of MTNR1A and MTNR1B receptors, with MTNR1A significantly higher in patients who succumbed to UM. Analysis of TCGA data from 80 UM patients revealed RNA expression for MTNR1A, RORα, and NQO2, but not MTNR1B or GPR50. Higher MTNR1A RNA levels were observed in patients with a BAP1 mutation, and higher NQO2 RNA levels were noted in patients with the epithelioid tumor cell type. However, Kaplan-Meier analysis did not show distinct survival probabilities based on receptor expression. The study concludes that UM clinical samples express melatonin receptors, suggesting a potential mechanism for melatonin's anti-cancer effects. Despite finding higher MTNR1A expression in patients who died of UM, no survival curve differences were observed. Further research is needed to explore additional mechanisms of melatonin’s oncostatic effects, including its antioxidant properties and immune modulation.