Social support, network, and relationships among coaches in different sports: a systematic review.

Introduction: The study aims to analyze scientific publications on the association between social networks, social relationships, and social support for sports coaches. It seeks to identify the types and levels of social support provided by various agents, and to understand the impact of this support on coaches' wellbeing. The goal is to help coaches better utilize social support, thereby enhancing their quality of life, work, and performance. Methods: This study systematically reviewed 11 scientific articles to investigate the association between social support, social networks, and social relationships in sports coaches. It aimed to identify the types and levels of social support offered to coaches by family members, peers, and friends. Our research utilized the PRISMA guidelines for systematic reviews and assessed study quality using the STROBE Statement. Eligibility was determined by the PECOS criterion based on the search strategy terms. Results: Our findings indicate that social support has significant positive effects on sports coaches. It enhances selfcompassion, prevents burnout symptoms, boosts job and life satisfaction, and reduces stress levels. Organizational support, characterized by clear guidelines, guidance, and autonomy, yielded positive outcomes. Conversely, the absence of social support correlated with negative outcomes for coaches, including lower self-compassion, increased stress and burnout symptoms, reduced job and life satisfaction, and heightened work-family conflict. Coaches' social networks encompassed family members, peers, friends, and other sources, with friends perceived as the most influential. Maintaining an effective social support network is crucial for coaches' performance and psychological wellbeing. Discussion: This systematic review emphasizes the importance of social support for coaches in both their personal and professional lives, noting its positive effects and the negative consequences of its absence. Given the demanding nature of coaching, improving social support systems can enhance coaches' wellbeing and the success of sports activities.

Comparative transcriptional analysis between susceptible and resistant populations of Aedes (Stegomyia) aegypti (Linnaeus, 1762) after malathion exposure.

Aedes aegypti is an important vector of arboviruses, including dengue, chikungunya and Zika. The application of synthetic insecticides is a frequently used strategy to control this insect. Malathion is an organophosphate insecticide that was widely used in Brazil in the 1980s and 1990s to control the adult form of A. aegypti. In situations where resistance to currently used insecticides is detected, the use of malathion may be resumed as a control measure. Many studies have confirmed resistance to malathion, however, comparative studies of differential gene expression of the entire transcriptome of resistant and susceptible insects are scarce. Therefore, understanding the molecular basis of resistance to this insecticide in this species is extremely important. In this paper, we present the first transcriptomic description of susceptible and resistant strains of A. aegypti challenged with malathion. Guided transcriptome assembly resulted in 39,904 transcripts, where 2133 differentially expressed transcripts were detected, and three were validated by RT-qPCR. Enrichment analysis for these identified transcripts resulted in 13 significant pathways (padj < 0.05), 8 associated with down-regulated and 5 with up-regulated transcripts in treated resistant insects. It was possible to divide the transcripts according to the mechanism of action into three main groups: (i) genes involved in detoxification metabolic pathways; (ii) genes of proteins located in the membrane/extracellular region; and (iii) genes related to DNA integration/function. These results are important in advancing knowledge of genes related to resistance mechanisms in this insect, enabling the development of effective technologies and strategies for managing insecticide resistance.

Lung cancer volume doubling time by computed tomography: A systematic review and meta-analysis.

AIM: Lung cancer growth rate influences screening strategies and treatment decisions. This review aims to provide an overview of primary lung cancer growth rate, quantified by volume doubling time (VDT) through computed tomography (CT) measurement. METHODS: Using PRISMA-DTA guideline, PubMed, EMBASE, and Web of Science were searched until March 2024 for studies reporting CT-measured VDT of pathologically confirmed primary lung cancer before intervention. Summary data were extracted from published reports by two independent researchers. Primary outcomes were pooled mean VDT of lung cancer by nodule type and histology, distribution of indolent lung cancer (defined as VDT>400 days or negative), and correlated factors. RESULTS: Thirty-three studies were eligible, comprising 3959 patients with primary lung cancer (mean age range:57.6-77.0 years; 60.0 % men). The pooled mean VDT for solid, part-solid, and nonsolid lung cancer were 207, 536, and 669 days, respectively (p < 0.001). When stratified by histology within solid lung cancer, the pooled mean VDT of adenocarcinoma, squamous cell carcinoma, small cell lung cancer, and others were 223, 140, 73, and 178 days, respectively (p < 0.001). Indolent lung cancer was observed in 34.9 % of lung cancer, predominantly in adenocarcinoma (68.9 %). Adenocarcinoma was associated with slower growth, whereas factors such as tumor size, solidity, TNM staging, and smoking history were positively associated with growth rates. CONCLUSIONS: Pooled mean VDT of solid lung cancer was approximately 207 days, demonstrating significant variability in histology yet remaining under the 400-day referral threshold. Key predictors of growth rate include histology, size, solidity, and smoking history, essential for tailoring early intervention strategies. TRIAL REGISTRATION NUMBER: CRD42023408069.

COVID-19 Vaccination in Liver Cirrhosis: Safety and Immune and Clinical Responses.

Introduction: Three years after the beginning of the SARS-CoV-2 pandemic, the safety and efficacy of COVID-19 vaccination in liver cirrhosis (LC) patients remain controversial. We aimed to study the safety, immunological, and clinical responses of LC patients to COVID-19 vaccination. Methods: Prospective multicentric study in adults with LC eligible for COVID-19 vaccination, without prior known infection. Patients were followed up until the timing of a booster dose, SARS-CoV-2 infection, or death. Spike-protein immunoglobulin G antibody titers for SARS-CoV-2 at 2 weeks, 3 months, and 6 months postvaccination were assessed. Antibody titers <33.8 binding antibody units (BAU)/mL were considered seronegative and <200 BAU/mL suboptimal. Postvaccination infection and its severity were registered. Results: We included 124 LC patients, 81% males, mean aged 61 ± 10 years, with a mean follow-up of 221 ± 26 days. Alcohol was the most common (61%) cause of cirrhosis, and 7% were under immunosuppressants for autoimmune hepatitis; 69% had portal hypertension, 42% had a previous decompensation, and 21% had a Child-Pugh-Turcotte score of B/C. The type of vaccine administrated was BNT162b2 (n = 59, 48%), ChAdOx1nCoV-19 (n = 45, 36%), mRNA-1273 (n = 14, 11%), and Ad26.COV2.S (n = 6, 5%). Eighteen percent of the patients reported adverse events after vaccination, none serious. Median [Q1; Q3] antibody titers were 1,185 [280; 2,080] BAU/mL at 2 weeks, 301 [72; 1,175] BAU/mL at 3 months, and 192 [49; 656] BAU/mL at 6 months. There were seronegative and suboptimal antibody responses in 8% and 23% of the patients at 2 weeks, 16% and 38% at 3 months, and 22% and 48% at 6 months. Older age and adenovirus vector vaccines were the only factors associated with seronegative and suboptimal responses at 2 weeks and 3 months (p < 0.05) in a multivariable logistic regression analysis. Eleven patients (9%) were infected with SARS-CoV-2 during follow-up (3.8-6.6 months postvaccination), all with mild disease. There were no differences regarding the type of vaccine, and 73% had antibody titers >200 BAU/mL at 3 months. Conclusion: COVID-19 vaccines in patients with LC were safe, without serious adverse events. The humoral and clinical responses were similar to the reported for the general population. Humoral response was adversely impacted by older age and adenovirus vector vaccines and unrelated to the liver disease severity.

Introdução: Três anos após o início da pandemia SARS-CoV-2, a segurança e eficácia da vacinação COVID-19 em doentes com cirrose hepática (CH) permanecem controversas. Pretendemos avaliar a segurança, respostas imunológica e clínica de doentes com CH às vacinas contra a COVID-19. Métodos: Estudo prospetivo multicêntrico em adultos com CH elegíveis para vacinação contra a COVID-19, sem infeção prévia conhecida. Os doentes foram acompanhados até ao momento da dose de reforço, infeção SARS-CoV-2 ou falecimento. Avaliámos os títulos de anticorpos IgG da proteína-Spike SARS-CoV-2 às 2 semanas, 3 meses e 6 meses. Títulos de anticorpos <33.8 BAU/mL foram considerados seronegativos e <200 BAU/mL subótimos. A ocorrência de infeção pós-vacinação e respetiva gravidade foram registadas. Resultados: Incluímos 124 doentes com CH, 81% homens, com idade média de 61 ± 10 anos e um seguimento médio de 221 ± 26 dias. A causa mais prevalente de cirrose foi o álcool (61%) e 7% dos doentes faziam terapêutica imunossupressora por hepatite autoimune. Existiam sinais de hipertensão portal em 69%, descompensação prévia em 42% e classificação de Child-Pugh-Turcotte B/C em 21%. O tipo de vacina administrada foi: BNT162b2 (n = 59, 48%), ChAdOx1nCoV-19 (n = 45, 36%), mRNA-1273 (n = 14, 11%) e Ad26.COV2.S (n = 6, 5%). Foram reportados efeitos adversos pós-vacinação em 18% dos participantes, nenhum deles grave. Os títulos medianos [Q1; Q3] de anticorpos foram 1.185 [280; 2.080] BAU/mL às 2 semanas, 301 [72; 1.175] BAU/mL aos 3 meses e 192 [49; 656] BAU/mL aos 6 meses. Observámos respostas humorais seronegativas e subótimas em 8% e 23% dos doentes às 2 semanas, 16% e 38% aos 3 meses e 22% e 48% aos 6 meses. A idade avançada e vacinas de vetor de adenovírus foram os únicos fatores associados a respostas seronegativas e subótimas às 2 semanas e 3 meses (p < 0.05) em análise de regressão logística multivariada. Onze doentes (9%) desenvolveram infeção SARS-CoV-2 durante o seguimento (3.8­6.6 meses pós vacinação), todos com doença ligeira. Não observámos diferenças relativamente ao tipo de vacina, apresentando 73% deles títulos de anticorpos >200 BAU/mL aos 3 meses. Conclusões: A vacinação contra a COVID-19 em doentes com CH foi segura, sem efeitos adversos graves. As respostas humoral e clínica foram semelhantes às reportadas na população geral. A resposta humoral foi afetada negativamente pela idade avançada e vacinas de vetor de adenovírus e não apresentou relação com a gravidade da doença hepática.

FLI and FIB-4 in diagnosing Metabolic Dysfunction-Associated Steatotic Liver Disease in Primary Care: High Prevalence and Risk of Significant Disease.

INTRODUCTION AND OBJECTIVES: Public health policies in metabolic dysfunction-associated steatotic liver disease (MASLD) are still lacking. This study aims to estimate the prevalence and severity of MASLD in primary health care (PHC) through non-invasive markers. PATIENTS AND METHODS: Two-phase study, including a retrospective (RETR) and a prospective (PROS) one, was carried out in PHC in Brazil. In RETR, metabolic and hepatic profiles of 12,054 patients, including FIB-4, were evaluated. In PROS, 350 patients were randomly selected and submitted to a clinical and nutritional assessment. RESULTS: RETR (65.4% women, mean age 55.3 years old): dyslipidemia, hypertension, and type 2 diabetes mellitus (T2DM) present in 40.8%, 34.3%, and 12.2% of the electronic health records, respectively. Fasting glucose >100 mg/dL in 34.5%, and glycated hemoglobin higher than 5.7% in 51.5%, total cholesterol >200mg/dL and triglycerides >150mg/dL in 40.8% and 32.1%, respectively. Median FIB-4 was of 1.33, 5% >2.67. No one had MASLD as a diagnostic hypothesis; PROS(71.8% women, mean age 58 years old): body mass index (BMI) ≥30 kg/m² in 31.8%. MASLD prevalence (FLI≥ 30 + cardiometabolic features) of 62.1%; 39.4% of patients had FLI ≥60, with higher BMI, waist circumference, fasting glucose, triglycerides, AST, ALT and GGT, as well as lower HDL-cholesterol (p<0.001). FIB-4>1.3 in 40% and NAFLD Fibrosis Score (NFS)>-1.45 in 59.2% of steatotic patients. CONCLUSIONS: There is a high prevalence of MASLD in PHC, with a significant risk of liver fibrosis. These findings reinforce we need to develop public policies to defeat MASLD epidemics.

Mycofenolate-induced ileocolitis.

Terminal ileitis is a common finding in clinical practice and is often associated with Crohn's disease. However, other pathologies must be considered particularly those resulting from side effects of drugs. We report a case of an 18-year-old female that underwent renal transplant under mycophenolate sodium, tacrolimus, and prednisolone admitted for abdominal pain, diarrhea and weight loss. Abdominal ultrasound revealed terminal ileum wall thickness, extending through 6,6 cm, while a subsequent Ileocolonoscopy revealed normal ileal mucosae but congestive cecum mucosae with superficial ulcers. Histology revealed unspecific chronic inflammation. Under the hypothesis of drug-induced enterocolitis, and after multidisciplinary discussion, mycophenolate sodium was suspended, with a rapid recovery without further treatment. This case highlights the challenge of diagnosing ileocolitis and demonstrates that MS-induced lesions can present clinical and endoscopic changes similar to those seen in Crohn's disease. Although enteric-coated MS has delayed absorption from the GI tract compared to MMF, which might reduce GI adverse events, this difference does not seem to be statistically significant.

Numerical analysis of blood flow in a branched modular stent-graft for aneurysms covering all zones of the aortic arch.

Due to the anatomical complexity of the aortic arch for the development of stent-grafts for total repair, this region remains without a validated and routinely used endovascular option. In this work, a modular stent-graft for aneurysms that covers all aortic arch zones, proposed by us and previously structurally evaluated, was evaluated from the point of view of haemodynamics using fluid-structural numerical simulations. Blood was assumed to be non-Newtonian shear-thinning using the Carreau model, and the arterial wall was assumed to be anisotropic hyperelastic using the Holzapfel model. Nitinol and expanded polytetrafluoroethylene (PTFE-e) were used as materials for the stents and the graft, respectively. Nitinol was modelled as a superelastic material with shape memory by the Auricchio model, and PTFE-e was modelled as an isotropic linear elastic material. To validate the numerical model, a silicone model representative of the aneurysmal aorta was subjected to tests on an experimental bench representative of the circulatory system. The numerical results showed that the stent-graft restored flow behaviour, making it less oscillatory, but increasing the strain rate, turbulence kinetic energy, and viscosity compared to the pathological case. Taking the mean of the entire cycle, the increase in turbulence kinetic energy was 198.82% in the brachiocephalic trunk, 144.63% in the left common carotid artery and 284.03% in the left subclavian artery after stent-graft implantation. Based on wall shear stress parameters, it was possible to identify that the internal branches of the stent-graft and the stent-graft fixation sites in the artery were the most favourable regions for the deposition and accumulation of thrombus. In these regions, the oscillating shear index reached the maximum value of 0.5 and the time-averaged wall shear stress was close to zero, which led the relative residence time to reach values above 15 Pa-1. The stent-graft was able to preserve flow in the supra-aortic branches.

Ulcerative colitis in remission symptoms: a response to anxiety or ongoing inflammation?

INTRODUCTION: Understand the cause of gastrointestinal symptoms compatible with irritable bowel syndrome (IBS) in patients with inflammatory bowel disease (IBD) in remission is challenging. Those patients are known to show more anxiety, that may influence the course of IBD. The aim of this study was to determine the prevalence of IBS-like symptoms and anxiety by a questionnaire, and his association with subclinical inflammation using calprotectin levels (FC), Mayo Endoscopic Score (MES) and Geboes score (GS) in patients with ulcerative colitis (UC) in clinical remission. METHODS: Recruitment occurred between January 2020 and December 2021 and included UC patients scheduled for colonoscopy. Clinical remission was defined by stool frequency, ulcerative colitis activity index and serum C-reactive protein. IBS diagnosis was evaluated by Roma IV criteria. RESULTS: We included 106 patients (51.9% women; mean age 51 years ±14.8). Rome IV criteria were fulfilled by 29 patients (27.4%). In the UC+IBS group more individuals had calprotectin >100mg/Kg (58.6% vs 23.4%, P=0.001), MES≥1 (37.9% vs 16.9%, P=0.023) and GS>2 (69.0% vs 29.9%, P=0.000). Thirty-three patients reported anxiety (31.3%). UC+IBS group also showed higher anxiety rates (51.7% vs 23.4, P=0.006). In multivariate logistic regression analyses: FC>100mg/Kg, histological activity, and higher anxiety were associated with IBS-like symptoms. CONCLUSION: IBS-like symptoms are common in UC patients considered in clinical remission and relates with anxiety and subclinical inflammation. Our findings underscore the necessity for a comprehensive strategy for these patients, targeting not only inflammation but also psychological conditions.

Effects of low dose computed tomography (LDCT) on lung cancer screening on incidence and mortality in regions with high tuberculosis prevalence: A systematic review.

BACKGROUND: Lung cancer screening (LCS) using low-dose computed tomography (LDCT) is a strategy for early-stage diagnosis. The implementation of LDCT screening in countries with a high prevalence/incidence of tuberculosis (TB) is controversial. This systematic review and meta-analysis aim to identify whether LCS using LDCT increases early-stage diagnosis and decreases mortality, as well as the false-positive rate, in regions with a high prevalence of TB. METHODS/DESIGN: Studies were identified by searching BVS, PUBMED, EMBASE, and SCOPUS. RCT and cohort studies (CS) that show the effects of LDCT in LC screening on mortality and secondary outcomes were eligible. Two independent reviewers evaluated eligibility and a third judged disagreements. We used the Systematic Review Data Repository (SRDR+) to extract the metadata and record decisions. The analyses were stratified by study design and incidence of TB. We used the Cochrane "Risk of bias" assessment tool. RESULTS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) were used. Thirty-seven papers were included, referring to 22 studies (10 RCTs and 12 cohorts). Few studies were from regions with a high incidence of TB (One RCT and four cohorts). Nonetheless, the evidence is compatible with European and USA studies. RCTs and CS also had consistent results. There is an increase in early-stage (I-II) diagnoses and reduced LC mortality in the LCDT arm compared to the control. Although false-positive rates varied, they stayed within the 20 to 30% range. DISCUSSION: This is the first meta-analysis of LDCT for LCS focused on its benefits in regions with an increased incidence/prevalence of TB. Although the specificity of Lung-RADS was higher in participants without TB sequelae than in those with TB sequelae, our findings point out that the difference does not invalidate implementing LDCT LCS in these regions. TRIAL REGISTRATION: Systematic review registration Systematic review registration PROSPERO CRD42022309581.

Global prevalence and characteristics of infections and clinical outcomes in hospitalised patients with cirrhosis: a prospective cohort study for the CLEARED Consortium.

BACKGROUND: Infections have a poor prognosis in inpatients with cirrhosis. We aimed to determine regional variations in infections and their association with clinical outcomes in a global cohort of inpatients with cirrhosis. METHODS: In this prospective cohort study initiated by the CLEARED Consortium, we enrolled adults (aged >18 years) with cirrhosis who were non-electively admitted to 98 hospitals from 26 countries or regions across six continents between Nov 5, 2021, and Dec 10, 2022. Data at admission, during hospitalisation, and for 30 days after discharge were collected through patient reports and chart reviews. Collected data included demographics; country and country income level per World Bank classifications (high-income countries [HICs], upper-middle-income countries [UMICs], and low-income or lower-middle-income countries [L-LMICs]); comorbidities; characteristics related to cirrhosis and the infections, including types, culture results, and drug resistance profile; antibiotic use; and disease course while hospitalised and for 30 days post-discharge. The primary outcome was in-hospital death or hospice referral in those with versus those without an admission infection (defined by the presence of infection on or within 48 h of admission). Multivariable log-binomial regression for in-hospital death or hospice referral was performed to identify risk factors. FINDINGS: Of 4550 patients screened, 4238 patients (mean age 56·1 years [SD 13·3]; 2711 [64·0%] male and 1527 [36·0%] female) with complete data were enrolled. 1351 (31·9%) had admission infections. A higher proportion of patients in L-LMICs had infections (318 [41·7%] of 762 vs 444 [58·3%] without infection) than in UMICs (588 [30·6%] of 1922 vs 1334 [69·4%]) or HICs (445 [28·6%] of 1554 vs 1109 [71·4%]). Patients with admission infections had worse severity of cirrhosis and were more likely to have had an infection or been hospitalised in the preceding 6 months. The most common specific infection types were spontaneous bacterial peritonitis (391 [28·9%] of 1351), pneumonia (233 [17·2%]), and urinary tract infections (193 [14·3%]). 549 (40·6%) patients were culture-positive for bacterial or fungal infections, with the lowest culture-positive rates in Africa and mainland China. Most of the isolated organisms were Gram-negative (345 [63%] of 549), then Gram-positive (157 [29%]), and then fungi or mixed (47 [9%]), with Escherichia coli, Klebsiella pneumoniae, and Enterococcus spp being the top three isolated pathogens. The overall rate of drug resistance was 40% (220 of 549 with positive cultures), being highest in UMICs. The most used empirical antimicrobials were third-generation cephalosporins (453 [37%] of 1241), followed by the broad-spectrum ß-lactams and ß-lactamase inhibitors (289 [23%]). De-escalation was observed in 62 (20%) of 304 patients who had their antibiotics changed. Patients with versus without admission infections had a higher rate of in-hospital death or hospice transfer (299 [22·1%] of 1351 vs 232 [8·0%] of 2887; p<0·0001), a result replicated in multivariable analysis (adjusted risk ratio 1·75 [95% CI 1·42-2·06]; p<0·0001). Older age, self-reported female gender, not being in a HIC, lactulose use, and higher MELD-Na score were also associated with in-hospital death or hospice transfer on multivariable analysis. INTERPRETATION: In the CLEARED Consortium cohort of inpatients with cirrhosis, the rates and types of infections, causative organisms, and culture-positivity varied substantially across regions, and infections were associated with a higher mortality risk. Culture positivity, which guides appropriate antibiotic use, was low. Taking a global perspective, considering regional variations in infections, drug resistance, and resources, could help to alleviate disparities in burden and outcomes. FUNDING: US Department of Veterans Affairs, the Richmond Institute for Veterans Research, the National Natural Science Foundation of China, Shanghai Rising-Star Program, the National Council for Scientific and Technological Development of Brazil, and Shanghai Municipal Key Clinical Specialty.

Strategic use of 4 % deltamethrin impregnated-collar in seropositive dogs reduces the incidence of seroreactivity to visceral leishmaniasis in dogs from endemic areas.

The effectiveness of a visceral leishmaniasis (VL) control strategy based on the application of 4 % deltamethrin impregnated collars (DIC) exclusively in seropositive dogs was assessed between 2018 and 2019, through a prospective study. The effectiveness of DIC-collaring was evaluated by comparing the incidence rate of anti-leishmanial antibodies among dogs from two endemic districts in Brazil. In one of the areas, the conventional control measure which is based on the non-compulsory euthanasia of LV seropositive dogs, was practiced by the official healthy service as a regular procedure, whereas strategic collaring, conceived in this study, was carried out in the other. Results of serological tests applied to serum samples collected from all domiciled dogs were evaluated in three consecutive times, spaced by around 200 days. Incidence rates of VL seroreactivity were compared between districts in the same period of time as well as within the same district, in consecutive periods. Based on the results, the risk of infection in the population under conventional control measure was up to four times higher than the risk of infection where DIC-collaring was used. The strategic use of collar proposed here emerged as a promising measure for VL control in dogs from endemic areas. Strategic collaring does not rely on the euthanasia of infected animals, an extremely controversial procedure, and instead of being used in all dogs, as collaring is normally recommended; only seropositive dogs are intervened. Strategic use of DIC has the potential to drastically reduce costs, if compared to mass collaring canine population.

Evaluation of four chatbots in autoimmune liver disease: A comparative analysis.

INTRODUCTION AND OBJECTIVES: Autoimmune liver diseases (AILDs) are rare and require precise evaluation, which is often challenging for medical providers. Chatbots are innovative solutions to assist healthcare professionals in clinical management. In our study, ten liver specialists systematically evaluated four chatbots to determine their utility as clinical decision support tools in the field of AILDs. MATERIALS AND METHODS: We constructed a 56-question questionnaire focusing on AILD evaluation, diagnosis, and management of Autoimmune Hepatitis (AIH), Primary Biliary Cholangitis (PBC), and Primary Sclerosing Cholangitis (PSC). Four chatbots -ChatGPT 3.5, Claude, Microsoft Copilot, and Google Bard- were presented with the questions in their free tiers in December 2023. Responses underwent critical evaluation by ten liver specialists using a standardized 1 to 10 Likert scale. The analysis included mean scores, the number of highest-rated replies, and the identification of common shortcomings in chatbots performance. RESULTS: Among the assessed chatbots, specialists rated Claude highest with a mean score of 7.37 (SD = 1.91), followed by ChatGPT (7.17, SD = 1.89), Microsoft Copilot (6.63, SD = 2.10), and Google Bard (6.52, SD = 2.27). Claude also excelled with 27 best-rated replies, outperforming ChatGPT (20), while Microsoft Copilot and Google Bard lagged with only 6 and 9, respectively. Common deficiencies included listing details over specific advice, limited dosing options, inaccuracies for pregnant patients, insufficient recent data, over-reliance on CT and MRI imaging, and inadequate discussion regarding off-label use and fibrates in PBC treatment. Notably, internet access for Microsoft Copilot and Google Bard did not enhance precision compared to pre-trained models. CONCLUSIONS: Chatbots hold promise in AILD support, but our study underscores key areas for improvement. Refinement is needed in providing specific advice, accuracy, and focused up-to-date information. Addressing these shortcomings is essential for enhancing the utility of chatbots in AILD management, guiding future development, and ensuring their effectiveness as clinical decision-support tools.

Time of day affects MrgD-dependent modulation of cardiomyocyte contractility.

The renin-angiotensin system (RAS) is composed of a series of peptides, receptors, and enzymes that play a pivotal role in maintaining cardiovascular homeostasis. Among the most important players in this system are the angiotensin-II and angiotensin-(1-7) peptides. Our group has recently demonstrated that alamandine (ALA), a peptide with structural and functional similarities to angiotensin-(1-7), interacts with cardiomyocytes, enhancing contractility via the Mas-related G protein-coupled receptor member D (MrgD). It is currently unknown whether this modulation varies along the distinct phases of the day. To address this issue, we assessed the ALA-induced contractility response of cardiomyocytes from mice at four Zeitgeber times (ZTs). At ZT2 (light phase), ALA enhanced cardiomyocyte shortening in an MrgD receptor-dependent manner, which was associated with nitric oxide (NO) production. At ZT14 (dark phase), ALA induced a negative modulation on the cardiomyocyte contraction. ß-Alanine, an MrgD agonist, reproduced the time-of-day effects of ALA on myocyte shortening. NG-nitro-l-arginine methyl ester, an NO synthase inhibitor, blocked the increase in fractional shortening induced by ALA at ZT2. No effect of ALA on myocyte shortening was observed at ZT8 and ZT20. Our results show that ALA/MrgD signaling in cardiomyocytes is subject to temporal modulation. This finding has significant implications for pharmacological approaches that combine chronotherapy for cardiac conditions triggered by disruption of circadian rhythms and hormonal signaling.NEW & NOTEWORTHY Alamandine, a member of the renin-angiotensin system, serves critical roles in cardioprotection, including the modulation of cardiomyocyte contractility. Whether this effect varies along the day is unknown. Our results provide evidence that alamandine via receptor MrgD exerts opposing actions on cardiomyocyte shortening, enhancing, or reducing contraction depending on the time of day. These findings may have significant implications for the development and effectiveness of future cardiac therapies.

Longitudinal Changes of CT-radiomic and Systemic Inflammatory Features Predict Survival in Advanced Non-Small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors.

PURPOSE: This study aims to determine whether longitudinal changes in CT radiomic features (RFs) and systemic inflammatory indices outperform single-time-point assessment in predicting survival in advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). MATERIALS AND METHODS: We retrospectively acquired pretreatment (T0) and first disease assessment (T1) RFs and systemic inflammatory indices from a single-center cohort of stage IV NSCLC patients and computed their delta (Δ) variation as [(T1-T0)/T0]. RFs from the primary tumor were selected for building baseline-radiomic (RAD) and Δ-RAD scores using the linear combination of standardized predictors detected by LASSO Cox regression models. Cox models were generated using clinical features alone or combined with baseline and Δ blood parameters and integrated with baseline-RAD and Δ-RAD. All models were 3-fold cross-validated. A prognostic index (PI) of each model was tested to stratify overall survival (OS) through Kaplan-Meier analysis. RESULTS: We included 90 ICI-treated NSCLC patients (median age 70 y [IQR=42 to 85], 63 males). Δ-RAD outperformed baseline-RAD for predicting OS [c-index: 0.632 (95%CI: 0.628 to 0.636) vs. 0.605 (95%CI: 0.601 to 0.608) in the test splits]. Integrating longitudinal changes of systemic inflammatory indices and Δ-RAD with clinical data led to the best model performance [Integrated-Δ model, c-index: 0.750 (95% CI: 0.749 to 0.751) in training and 0.718 (95% CI: 0.715 to 0.721) in testing splits]. PI enabled significant OS stratification within all the models (P-value <0.01), reaching the greatest discriminative ability in Δ models (high-risk group HR up to 7.37, 95% CI: 3.9 to 13.94, P<0.01). CONCLUSION: Δ-RAD improved OS prediction compared with single-time-point radiomic in advanced ICI-treated NSCLC. Integrating Δ-RAD with a longitudinal assessment of clinical and laboratory data further improved the prognostic performance.

Firmicutes/Bacteroidetes and Firmicutes/Proteobacteria ratios are associated with worse prognosis in a cohort of Latin American patients with cirrhosis.

BACKGROUND: Some evidence suggests an association between gut dysbiosis and cirrhosis progression. The authors investigated Gut Microbiome (GM) influence on 90-day mortality and hospitalization/rehospitalization rates in cirrhotic patients. METHODS: Compensated/decompensated outpatients and decompensated inpatients were prospectively included and compared to healthy controls. Clinical, laboratory, GM, and two ratios between phyla were evaluated. Patients were followed up for 90 days for hospitalization/rehospitalization and mortality. RESULTS: 165 individuals were included (50 compensated, 49 decompensated outpatients; 36 decompensated inpatients; 30 healthy), 48.5 % female, mean age was 61, main cirrhosis etiology was hepatitis C (27.3 %), and mostly Child-Pugh (CP) B patients, median MELD of 13. As liver disease progressed, microbiota diversity decreased between the groups (p = 0.05; p < 0.004). There were 9 deaths and 22 hospitalizations or rehospitalizations. GM composition had correlation with norfloxacin (p = 0.36, p = 0.04), encephalopathy (p = 0.31, p = 0.01), lactulose (p = 0.26, p = 0.01), 90-day mortality (p = 0.22, p = 0.04), CP (p = 0.17, p = 0.01), previous 6-month antibiotic use (p = 0.16, p = 0.01), MELD (p = 0.145, p = 0.01), ALBI (p = 0.1, p = 0.04) and 90-day hospitalization/rehospitalization (p = 0.08, p = 0.03). Firmicutes/Bacteroidetes (F/B) and Firmicutes/Proteobacteria (F/P) ratios were progressively lower and more significant and had an association with 90-day mortality (p < 0.001). Three MELD set-points (≥ 15, 18 and 20) were significantly associated with both ratios, with similar accuracies. CONCLUSIONS: GM dysbiosis was associated with higher CP, MELD, 90-day mortality and hospitalization/rehospitalization. F/B and F/P ratios were associated with 90-day mortality.

Redefining the Role of Ornithine Aspartate and Vitamin E in Metabolic-Dysfunction-Associated Steatotic Liver Disease through Its Biochemical Properties.

It is known that the inflammation process leading to oxidative stress and thyroid hormone metabolism dysfunction is highly altered in metabolic dysfunction associated with steatotic liver disease (MASLD). This study aims to address the effect of ornithine aspartate (LOLA) and vitamin E (VitE) in improving these processes. Adult Sprague-Dawley rats were assigned to five groups and treated for 28 weeks: controls (n = 10) received a standard diet (for 28 weeks) plus gavage with distilled water (DW) from weeks 16 to 28. MASLD groups received a high-fat and choline-deficient diet for 28 weeks (MASLD group) and daily gavage with 200 mg/kg/day of LOLA, or twice a week with 150 mg of VitE from weeks 16-28. LOLA diminished collagen deposition (p = 0.006). The same treatment diminished carbonyl, TBARS, and sulfhydryl levels and GPx activity (p < 0.001). Type 3 deiodinase increased in the MASLD group, downregulating T3-controlled genes, which was corrected in the presence of LOLA. LOLA also promoted a near-normalization of complex II, SDH, and GDH activities (p < 0.001) and improved reticulum stress, with a reduction in GRP78 and HSPA9/GRP75 protein levels (p < 0.05). The enhanced energy production and metabolism of thyroid hormones, probably because of GSH replenishment provided by the L-glutamate portion of LOLA, opens a new therapeutic approach for MASLD.

Transarterial embolization is an acceptable bridging therapy to hepatocellular carcinoma prior to liver transplantation.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive malignant neoplasm that requires liver transplantation (LT). Despite patients with HCC being prioritized by most organ allocation systems worldwide, they still have to wait for long periods. Locoregional therapies (LRTs) are employed as bridging therapies in patients with HCC awaiting LT. Although largely used in the past, transarterial embolization (TAE) has been replaced by transarterial chemoembolization (TACE). However, the superiority of TACE over TAE has not been consistently shown in the literature. AIM: To compare the outcomes of TACE and TAE in patients with HCC awaiting LT. METHODS: All consecutive patients with HCC awaiting LT between 2011 and 2020 at a single center were included. All patients underwent LRT with either TACE or TAE. Some patients also underwent percutaneous ethanol injection (PEI), concomitantly or in different treatment sessions. The choice of LRT for each HCC nodule was determined by a multidisciplinary consensus. The primary outcome was waitlist dropout due to tumor progression, and the secondary outcome was the occurrence of adverse events. In the subset of patients who underwent LT, complete pathological response and post-transplant recurrence-free survival were also assessed. RESULTS: Twelve (18.5%) patients in the TACE group (only TACE and TACE + PEI; n = 65) and 3 (7.9%) patients in the TAE group (only TAE and TAE + PEI; n = 38) dropped out of the waitlist due to tumor progression (P log-rank test = 0.29). Adverse events occurred in 8 (12.3%) and 2 (5.3%) patients in the TACE and TAE groups, respectively (P = 0.316). Forty-eight (73.8%) of the 65 patients in the TACE group and 29 (76.3%) of the 38 patients in the TAE group underwent LT (P = 0.818). Among these patients, complete pathological response was detected in 7 (14.6%) and 9 (31%) patients in the TACE and TAE groups, respectively (P = 0.145). Post-LT, HCC recurred in 9 (18.8%) and 4 (13.8%) patients in the TACE and TAE groups, respectively (P = 0.756). Posttransplant recurrence-free survival was similar between the groups (P log-rank test = 0.71). CONCLUSION: Dropout rates and posttransplant recurrence-free survival of TAE were similar to those of TACE in patients with HCC. Our study reinforces the hypothesis that TACE is not superior to TAE as a bridging therapy to LT in patients with HCC.

Muscle fibre morphometric analysis (MusMA) correlates with muscle function and cardiovascular risk prognosis.

Morphometry of striated muscle fibres is critical for monitoring muscle health and function. Here, we evaluated functional parameters of skeletal and cardiac striated muscle in two experimental models using the Morphometric Analysis of Muscle Fibre tool (MusMA). The collagen-induced arthritis model was used to evaluate the function of skeletal striated muscle and the non-alcoholic fatty liver disease model was used for cardiac striated muscle analysis. After euthanasia, we used haeamatoxylin and eosin stained sections of skeletal and cardiac muscle to perform muscle fibre segmentation and morphometric analysis. Morphometric analysis classified muscle fibres into six subpopulations: normal, regular hypertrophic, irregular hypertrophic, irregular, irregular atrophic and regular atrophic. The percentage of atrophic fibres was associated with lower walking speed (p = 0.009) and lower body weight (p = 0.026), respectively. Fibres categorized as normal were associated with maximum grip strength (p < 0.001) and higher march speed (p < 0.001). In the evaluation of cardiac striated muscle fibres, the percentage of normal cardiomyocytes negatively correlated with cardiovascular risk markers such as the presence of abdominal adipose tissue (p = .003), miR-33a expression (p = .001) and the expression of miR-126 (p = .042) Furthermore, the percentage of atrophic cardiomyocytes correlated significantly with the Castelli risk index II (p = .014). MusMA is a simple and objective tool that allows the screening of striated muscle fibre morphometry, which can complement the diagnosis of muscle diseases while providing functional and prognostic information in basic and clinical research.

Smoking, mortality, access to diagnosis, and treatment of lung cancer in Brazil.

INTRODUCTION: Lung cancer (LC) is a relevant public health problem in Brazil and worldwide, given its high incidence and mortality. Thus, the objective of this study is to analyze the distribution of smoking and smoking status according to sociodemographic characteristics and disparities in access, treatment, and mortality due to LC in Brazil in 2013 and 2019. METHOD: Retrospective study of triangulation of national data sources: a) analysis of the distribution of smoking, based on the National Survey of Health (PNS); b) investigation of LC records via Hospital-based Cancer Registry (HCR); and c) distribution of mortality due to LC in the Mortality Information System (SIM). RESULTS: There was a decrease in the percentage of people who had never smoked from 2013 (68.5%) to 2019 (60.2%) and in smoking history (pack-years). This was observed to be greater in men, people of older age groups, and those with less education. Concerning patients registered in the HCR, entry into the healthcare service occurs at the age of 50, and only 19% have never smoked. While smokers in the population are mainly Mixed-race, patients in the HCR are primarily White. As for the initial stage (I and II), it is more common in White people and people who have never smoked. The mortality rate varied from 1.00 for people with higher education to 3.36 for people without education. Furthermore, White people have a mortality rate three times higher than that of Black and mixed-race people. CONCLUSION: This article highlighted relevant sociodemographic disparities in access to LC diagnosis, treatment, and mortality. Therefore, the recommendation is to strengthen the Population-Based Cancer Registry and develop and implement a nationwide LC screening strategy in Brazil since combined prevention and early diagnosis strategies work better in controlling mortality from the disease and continued investment in tobacco prevention and control policies.

Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease.

BACKGROUND: Metabolic-dysfunction associated steatotic liver disease (MASLD) is a hepatic manifestation of metabolic syndrome. Studies suggest ornithine aspartate (LOLA) as drug therapy. AIM: To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD. METHODS: Adult male Sprague Dawley rats were randomized into three groups: Control (10 rats fed with a standard diet), MASLD (10 rats fed with a high-fat and choline-deficient diet), and LOLA (10 rats receiving 200 mg/kg/d LOLA, after the 16th week receiving high-fat and choline-deficient diet). After 28 wk of the experiment, animals were euthanized, and feces present in the intestine were collected. Following fecal DNA extraction, the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™ system. RESULTS: Alpha and beta diversity metrics were comparable between MASLD and LOLA. 3 OTUs were differentially abundant between MASLD and LOLA, which belong to the species Helicobacter rodentium, Parabacteroides goldsteinii, and Parabacteroides distasonis. The functional prediction provided two different metabolic profiles between MASLD and LOLA. The 9 pathways differentially abundant in MASLD are related to a change in energy source, adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis. The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate, including tricarboxylic acid cycle pathways, purine/guanosine nucleotides biosynthesis, pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis. CONCLUSION: Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD, it was associated with changes in specific gut microbes and their related metabolic pathways.