This study describes the implementation of an interdisciplinary model within the COVID-19 cohort at Hospital das Clínicas, Universidade de São Paulo (HCFMUSP). Among 1957 survivors, 749 attended the first follow-up (6‒11 months), revealing that 83% reported persistent symptoms ‒ mainly fatigue, dizziness, pain, and dyspnea ‒ highlighting the need for extended monitoring. A four-year program involving 22 study groups was established to characterize symptom frequency, severity and disability, explore clinical and sociodemographic associations, and evaluate the potential for recovery through multidisciplinary approaches. A dedicated team coordinated recruitment, teleconsultations, in-person assessments and database management. Of 749 patients, 523 completed teleconsultations, 433 attended the first visit, and 367 the second. The implementation demonstrated that interdisciplinary research enhances patient engagement, reduces fragmentation, and supports efficient and high-quality research in complex human-based studies.
Aging has a significant impact on health, leading to changes in body composition and physical functionality in older adults. Given the relevance of this topic, the aim of this study was to analyze the effects of vitamin D supplementation combined with physical exercise over a 12-week period on body composition and metabolic profile in elderly women. The study followed a clinical approach, employing a randomized, double-blind, placebo-controlled trial, in accordance with the guidelines established by the Consolidated Standards of Reporting Trials (CONSORT), conducted at the Movement Studies Laboratory in São Paulo, Brazil. Analyses were performed using an intention-to-treat approach with random effects regression models. The study sample consisted of 46 elderly individuals, divided into two groups with 23 participants each. The experimental group received vitamin D3 supplementation at a dose of 49,000 IU/week, while the placebo group received seven capsules of the same size, volume, and color, containing lactose but no vitamin D3. After analyzing the results, it was observed that the groups were homogeneous in terms of age (p = 0.7658) and BMI (p = 0.5904). The results showed differences in 25-OH vitamin D levels (p < 0.001) between the groups over time. In conclusion, vitamin D supplementation successfully increased serum levels but failed to provide additional benefits for muscle mass or metabolic markers compared to resistance training alone.
Prevention, screening and diagnostic services for hepatitis B virus (HBV) and hepatitis C virus (HCV) can prevent morbidity and mortality in people receiving HIV care. However, there is limited information about the availability of HBV and HCV services at HIV clinics globally. The International epidemiology Databases to Evaluate AIDS (IeDEA) conducted surveys of service delivery and practices at participating HIV treatment centers from seven regions. We used 2023 survey data to measure availability of HBV vaccination, HBV and HCV screening, HBV surface antigen (HBsAg), HBV DNA, HCV antibody, HCV RNA testing. Multivariable logistic regression models were used to test associations of site characteristics with HBV and HCV services. HBV vaccination was available on-site at 67.7% of 204 HIV treatment sites. Screening for HBV and HCV at HIV care enrollment was reported by 72.1% and 50% of sites, respectively. HBsAg, HBV DNA, HCV antibody and HCV RNA testing were available on-site at 77%, 47.6%, 61.8% and 44.6% of sites, respectively. Sites serving predominately rural (vs. urban) populations were less likely to report on-site availability of HBV DNA (odds ratio (OR):0.07; 95% confidence interval (CI):0.01-0.68;P=0.02), HCV antibody (OR=0.18; 95% CI:0.04-0.92;P=0.04) and HCV RNA (OR=0.10; 95% CI:0.01-0.90;P=0.04) testing. Life-saving services such as HBV vaccination, HBsAg and HCV antibody testing were available on-site at most HIV treatment sites participating in the IeDEA network. Lower availability at rural sites suggests that expansion of services is important to eliminate HBV and HCV as public health problems in people receiving HIV care.
To describe baseline characteristics of a multinational, multiethnic Latin American cohort of SLE patients with and without lupus nephritis (LN) from Latin American Group for the Study of Lupus (GLADEL) 2.0. GLADEL 2.0 is an observational prevalent and incident cohort. Adult patients (≥18 years) with SLE who fulfilled the 1982/1997 American College of Rheumatology (ACR) and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria from 43 centres in 10 Latin American countries were categorised into four groups: (1) without LN, (2) prevalent inactive LN, (3) prevalent active LN and (4) incident LN. Baseline demographics, clinical manifestations, treatments, disease activity and damage were recorded. A cross-sectional analysis and logistic regression was conducted to identify factors associated with LN and cumulative damage (SLICC/ACR Damage Index (SDI)). Among 1083 patients, 89.6% were female, median age at diagnosis was 27 years, median disease duration was 66.2 months and 65.0% were Mestizo. Patients with LN (n=653) were younger and had shorter disease duration than patients without LN. LN was negatively associated with older age at diagnosis (OR, 0.98) and discoid rash (OR, 0.53) and positively associated with male gender (OR, 1.91), Mestizo ethnicity (OR, 1.46), comorbidities (OR, 3.2), thrombocytopenia (OR, 3.44), anti-double-stranded DNA (anti-dsDNA) positivity (OR, 3.23) and low complement (OR, 1.54). SDI ≥1 was associated with older age at diagnosis, longer disease duration, cumulative prednisone dose and cyclophosphamide use. Male sex, Mestizo ethnicity, comorbidities, thrombocytopenia, anti-dsDNA positivity and low complement levels were associated with LN occurrence. Cumulative damage was associated with older age at diagnosis, longer disease duration, higher cumulative dose of prednisone and the use of cyclophosphamide. NCT04534647.
Digital transformation in health is driven by Information and Communication Technologies integration and guided by institutional guidelines. Despite multiple models, no consensus exists on assessing facility-level digital health maturity, including organizational capacity and workflows. To present the preliminary results of Mapping Digital Health (DH) initiatives and Technological Requirements (TR) conducted in public healthcare facilities in São Paulo State. This descriptive observational study was conducted from March to August 2025 in public healthcare facilities (n = 6,319) across 17 Regional Health Departments in Sao Paulo State. A general sample target of 3,719 facilities was calculated, with specific targets by type: primary healthcare units (n = 2,570), specialty outpatient clinics (AME) (n = 62), hospitals (n = 529), emergency care units (n = 381), and prison units (n = 177). Two questionnaires (26 and 28 items across six and seven domains, respectively) were structured based on key technical and policy reference documents and covered essential domains for assessing DH maturity and TR. Responses on a five-point Likert scale were used to calculate maturity indices classified as incipient, developing, collaborative, or advanced. Questionnaires responses included 5,325 for DH and for 5,069 TR questionnaires. Prison units and AME met 100% of their response targets, while PHU, emergency care units, and hospitals achieved around 80%. Overall, Sao Paulo State scored 42.0 for DH and 45.7 for TR, both classified as "developing," considered an intermediate stage and reflects a moderate maturity. Prisons units and AME exhibited the highest scores in DH maturity and TR, respectively. Sao Paulo State shows an intermediate stage of digital health and technological requirement maturity, despite inequalities across facility typologies. The facility-level maturity index enabled a detailed analysis and may contribute to future public policies, training initiatives, and infrastructure investments.
Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS), a common sleep-related breathing disorder, is closely associated with an increased risk of cardiovascular and metabolic comorbidities. Polysomnography, the diagnostic gold standard, is costly and environmentally sensitive. This study explored the diagnostic potential of miR-1180-3p and its role in Chronic Intermittent Hypoxia (CIH)-induced vascular injury. Serum miR-1180-3p and CERS1 levels were measured in 112 OSAHS patients and 88 controls via qRT-PCR. Correlations with PSG parameters (LSpO₂, AHI, TS90%) were analyzed. In vitro, HUVECs were exposed to CIH, and miR-1180-3p effects on cell viability, apoptosis, and oxidative stress (MDA, SOD, GSH-Px) were assessed. TargetScan and dual-luciferase assays validated miR-1180-3p-CERS1 binding. Evaluating miR-1180-3p/CERS1 axis regulation of OSAHS pathogenesis via co-inhibition experiments. A significant upregulation of miR-1180-3p was detected in OSAHS patients (p < 0.001). miR-1180-3p served as an independent risk factor for OSAHS (OR = 5.405, 95% CI 2.247‒13.001) and held diagnostic value (AUC = 0.882). miR-1180-3p correlated negatively with LSpO2 (r = -0.705) but positively with AHI (r = 0.676) and TS90% (r = 0.774), with correlations persisting across mild, moderate, and severe OSAHS subgroups. In CIH-treated HUVECs, miR-1180-3p inhibition restored cell viability, reduced apoptosis, and alleviated oxidative stress. CERS1 was confirmed as a direct target, and its silencing reversed miR-1180-3p inhibition-mediated protection. miR-1180-3p was a novel diagnostic biomarker for OSAHS. By targeting CERS1, miR-1180-3p exacerbated CIH-induced damage to HUVECs, thereby regulating the pathological progression of OSAHS.
Adipose tissue is used in several specialties to obtain Adipose-derived Stem Cells (ASC) and fat derivatives. Several studies analyze protocols for harvesting fat tissues. However, these studies showed inconclusive data regarding cell viability and function. Thus, the objective of this study was to analyze protocols regarding cell viability, identify the best method, and test cell differentiation and proliferation when using the chosen methods. This study harvested lipoaspirate products from three healthy women undergoing aesthetic procedures. The first analysis corresponds to the viability of fat tissue liposuction products for the washing process. The second analyzes the effect of anesthetic drugs, and the third analyzes the cytotoxicity of the fraction process. After testing all these steps, the authors prepared the fat tissue using the best method chosen after the first analysis to test cell differentiation (adipogenesis, osteogenesis, and chondrogenesis) and proliferation. The analysis showed that saline solution 0.9% was the washing solution that induced less cell death. Regarding anesthetic and vasoconstrictor drugs, lidocaine, ropivacaine, and epinephrine caused similar levels of cell death, but sodium bicarbonate increased cell proliferation. The number of passages through a 2.4 mm Luer-to-Luer transfer device did not influence cell viability. The proliferation and differentiation of ASC in adipocytes, osteoblasts, and chondrocytes were preserved using saline solution 0.9% and 20 × passages for fat fractioning. The findings of this study provide preliminary in vitro evidence that may improve future investigations on the fat harvesting process.
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Functional Threshold Power (FTP) is widely used for performance evaluation and training prescription in endurance sports. Although FTP is strongly associated with power at the Respiratory Compensation Point (RCP), its interchangeability remains debated. This study examined the relationship and agreement between FTP and RCP in amateur triathletes and tested whether sex influences this relationship. Forty-nine amateur triathletes (male and female) participated. Each athlete completed a maximal cardiorespiratory cycling test and an FTP test, separated by at least 72 h. Linear regression models were used to test the association between FTP and RCP. A regression model including the interaction term (FTP × sex), equivalent to an ANCOVA framework, was applied to assess sex effects on the FTP-RCP relationship. Agreement between methods was assessed using Bland-Altman analysis. Two-way analysis of variance (ANOVA) was performed to examine the effects of sex, test type, and their interaction on absolute power (W), power relative to total body mass, and power relative to lean mass. FTP and RCP were strongly correlated (r = 0.916; p < 0.001). The interaction term FTP × sex was not significant (β = -0.135, p = 0.524), indicating that the regression slopes do not differ between males and females. Thus, the relationship between FTP and RCP was statistically similar across sexes. However, Bland-Altman analysis revealed wide limits of agreement, indicating poor interchangeability between FTP and RCP at the individual level. FTP is strongly associated with RCP, and the relationship is independent of sex. Despite this association, FTP and RCP are not interchangeable measures. Caution is warranted when using FTP as a direct surrogate for RCP in training prescription and performance assessment.
Critical Velocity (CV) is widely used to assess aerobic performance in endurance sports. Studies have compared protocols for CV determination in elite athletes. However, knowledge on the influence of the assessment protocol on CV and sex-based differences on metabolic responses at critical swimming velocity is limited. This study aims to compare different protocols for determining CV in swimming among male and female triathletes and to compare sex-based differences in the metabolic and perceived exertion responses after swimming 750 m at CV estimated by the three-parameter model. Highly trained amateur triathletes (12 men, 35.7 ± 11.0 years; 10 women, 38.1 ± 6.0 years) performed maximal swimming tests (50, 100, 200, and 400 m) to estimate Critical Velocity (CV). Each completed a 750 m swim at the CV determined by the three-parameter protocol (100-200-400 m), with monitoring of metabolic responses (lactate level and heart rate) and pain, dyspnea, and subjective perceived exertion. The four-distance protocol yielded the highest CV in both sexes, whereas the protocol based on 92% of the 400 m time produced the lowest values (p < 0.001). After the 750 m swim, men showed higher ratings of perceived exertion (p = 0.005), pain (p < 0.001), dyspnea (p < 0.001), and blood lactate concentration (p < 0.001) than women. The protocol used to determine CV significantly influences estimated values. Importantly, all findings related to physiological and perceptual responses during the 750 m swim are specific to the CV determined by the three-parameter protocol and should not be generalized to other CV determination methods. Under this protocol, CV may be associated with an exercise intensity approaching the severe domain; however, this interpretation should be made with caution.
Hypertensive heart disease with heart failure is a severe cardiovascular condition with high mortality rates. The relationship between the Lactate Dehydrogenase to Albumin Ratio (LAR) and mortality in these patients remains unclear. The authors analyzed 3019 patients with hypertensive heart failure using data from the MIMIC-IV database. Cox regression models were used to assess the association between LAR and mortality, with adjustments for various covariates. Restricted cubic spline analysis was employed to evaluate the threshold effect of LAR on mortality. Kaplan-Meier survival curves and subgroup analyses further explored the impact of LAR. LAR was significantly associated with increased mortality across all time points: hospital mortality (HR = 4.86, 95% CI 4.12 to 5.73; p < 0.001), 30-day mortality (HR = 4.16, 95% CI 3.56 to 4.87; p < 0.001), 90-day mortality (HR = 3.56, 95% CI 3.08 to 4.12; p < 0.001), and 365-day mortality (HR = 2.91, 95% CI 2.54 to 3.33; p < 0.001). These associations remained significant after multivariable adjustments. The Cox regression model with restricted cubic spline analysis revealed a threshold effect of LAR on mortality, with turning points at 1.662 for hospital mortality, 2.393 for 30-day mortality, 2.407 for 90-day mortality, and 2.406 for 365-day mortality (all p < 0.001 for non-linear tests). Kaplan-Meier survival curves showed significant differences in survival across LAR quartiles for all mortality outcomes (all p < 0.001). The LAR is significantly associated with mortality in critically ill patients, with a clear threshold effect. LAR may serve as a potential prognostic marker for identifying high-risk patients.
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A 10-year-old intact male Rottweiler was presented with a large, rapidly growing subcutaneous mass on the right thoracic limb. Physical examination revealed a firm, raised, non-ulcerated mass extending from the proximal scapula to the distal humerus. Cytological evaluation identified a highly cellular population of vacuolated cells with marked anisocytosis and anisokaryosis, consistent with a lipid-rich mesenchymal neoplasm. Histopathology of incisional biopsies confirmed a well-differentiated, low-grade subcutaneous liposarcoma. The owner declined therapeutic and surgical treatments. The dog died 3 months after diagnosis, with clinical signs suggestive of metastatic disease. This case highlights the importance of comprehensive tumour assessment for accurate grading, staging and effective management of canine soft tissue sarcomas, including liposarcomas. Liposarcoma should be considered a differential diagnosis for subcutaneous masses in the proximal limbs of dogs. Early diagnosis, accurate grading, complete staging and prompt surgical intervention, including limb amputation if warranted, are critical even for histologically well-differentiated, low-grade variants.
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Carpal Tunnel Syndrome (CTS) is a common entrapment neuropathy leading to pain and functional impairment. While smoking has been proposed as a modifiable risk factor, evidence from observational studies remains inconsistent due to potential confounding and reverse causality. The authors performed a two-sample Mendelian Randomization (MR) analysis to assess the causal relationship. Genetic instruments for five smoking phenotypes were derived from large-scale Genome-Wide Association Studies (GWAS). Summary-level data for CTS were obtained from the FinnGen Consortium (n = 480,201). The Inverse Variance Weighted (IVW) method was the primary analysis, supplemented by four other MR methods and a suite of sensitivity analyses to assess robustness and pleiotropy. Genetically predicted smoking propensity was associated with a higher risk of CTS. Specifically, genetic predisposition to smoking initiation (ORMR-IVW = 1.53; 95% CI 1.33-1.76; p < 0.001) and heavier cigarette consumption (ORMR-IVW = 1.52; 95% CI: 1.31-1.77; p < 0.001) significantly increased CTS risk. The estimate for current smoking was particularly strong (ORMR-IVW=3.96; 95% CI 2.20-7.12; p < 0.001). Sensitivity analyses were largely consistent, though some heterogeneity and potential pleiotropy were detected for specific phenotypes. This MR study supports a causal role of smoking in the development of CTS. These findings underscore the importance of smoking cessation as a potential preventive measure against CTS and should be integrated into patient counseling and public health strategies.
BOS172722, a selective TTK inhibitor, shows promise for Breast Cancer (BC) treatment. The role of gut microbiota as a potential mediator in this process has not been established. This Mendelian Randomization (MR) study investigated the causal effect of TTK inhibition on BC and conducted an exploratory analysis of potential mediation by gut microbiota. A two-step, two-sample drug target MR analysis used IEU Open GWAS project datasets. The inverse-variance-weighted method estimated causal effects, with sensitivity tests confirming robustness. False Discovery Rate (FDR) correction was applied to analyses for all microbial taxa. Genetically predicted TTK inhibition significantly reduced BC risk (OR = 0.667, 95 % CI 0.543-0.819; FDR-adjusted p < 0.001). In secondary analyses, initial uncorrected results indicated nominal associations between TTK inhibition and 20 gut microbial taxa, and between 6 taxa and BC risk. However, none of these microbiota-related associations remained statistically significant after FDR correction (all q-values >0.1). An exploratory mediation analysis on Genus Anaerostipes id.1991, which showed the strongest nominal signals (TTK inhibition on Anaerostipes: uncorrected p = 0.003; Anaerostipes on BC: uncorrected p = 0.025), was performed for hypothesis generation only; no statistically significant mediation was observed. This study provides robust genetic evidence that TTK inhibition is causally associated with a decreased risk of breast cancer. The exploratory analysis of gut microbiota as a mediator did not yield statistically significant results after correction for multiple testing. The potential role of specific microbes, such as Genus Anaerostipes, remains inconclusive and requires further dedicated investigation.
Pancreatic Cancer (PC) is a highly aggressive malignancy with a dismal prognosis, primarily due to late-stage diagnosis and limited therapeutic options. This study aimed to identify potential biomarkers involved in PC progression and immune microenvironment modulation. RNA sequencing data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were integrated to identify differentially expressed genes. Mendelian Randomization (MR) analysis was conducted to assess causal associations between candidate genes and PC risk. Immune cell infiltration was evaluated using the CIBERSORT algorithm, and mediation analysis explored the role of immune cells in PC progression. Validation was performed using RT-qPCR and immunohistochemistry in clinical tissue samples. CLIC3 and MST1R were significantly overexpressed in PC tissues and associated with advanced tumor stages. MR analysis confirmed their causal relationship with PC, with Odds Ratios of 2.36 (95% CI: 1.58-3.51) for CLIC3 and 1.30 (95% CI: 1.06-1.60) for MST1R. High expression of these genes correlated with increased M0 macrophages and decreased CD8⁺ T cells, CD4⁺ T-cells, and naïve B-cells, suggesting immune dysregulation. Mediation analysis emphasized the pivotal role of CD8⁺ cytotoxic T-cells in PC progression. Moreover, CLIC3 and MST1R were closely associated with immune checkpoint molecules CD276 and NT5E. CLIC3 and MST1R are overexpressed and causally implicated in pancreatic cancer development and immune modulation. They represent promising biomarkers and potential therapeutic targets for precision immunotherapy in PC.
Organ preservation at low temperatures has been described since Alexis Carrel's time in 1912. Since then, organs have been stored in a mixture of frozen saline solution and liquid, with a temperature of around 4 °C. Studies suggest higher temperatures may preserve mitochondrial function, allowing for an extended ischemia time. Various systems are commercially available, each with different preservation principles. This study aims to analyze the underlying parameters of each device. A systematic review was conducted using the following databases: PubMed, Embase, and Cochrane Library, searching for clinical trials and observational studies evaluating the use of thermal boxes for lung preservation devices in transplantation. The assessed outcomes were Primary Graft Dysfunction (PGD), ventilation time, length of hospital stay, rejection rate, and survival rate. The search yielded six studies selected based on title and abstract, including 519 lung transplant cases. The preservation systems evaluated were LUNGguard and MYTEMPF. Our studies assessed LUNGguard, with a total of 298 patients. This system maintained an average temperature of 6 °C (4° to 8 °C), and 51 patients developed grade 3 PGD within 72 h. The mean ventilation time was 25.2 h (25 to 25.5 h), and ICU stay ranged from 8 to 9 days. Rejection was observed in 3 out of 18 patients, and hospital survival was reported in 221 out of 231 patients. MYTEMP 65 HC was evaluated in one study with 70 patients, of whom 4 developed grade 3 PGD within 72 h. The mean ventilation time was 49 h, and the length of hospital stay was 25 days. Kaplan-Meier estimated survival was 94 % (HR = 0.65; 95 % CI 0.26 to 1.6). Preservation systems show different performances in lung preservation devices for transplantation. Across available studies, LUNGguard has been reported to maintain temperature stability with corresponding survival findings. Across studies of MYTEMP, lower grade 3 PGD rates have been reported, together with longer ventilation and hospitalization durations, and the device is described as non-transport. Other devices exist on the market, but their data remains unpublished. In summary, ongoing clinical studies with these and other preservation devices are expected to provide new evidence in the near future. As additional data become available, an updated systematic review will help clarify their comparative performance and guide clinical practice.
To evaluate the impact of the COVID-19 pandemic on outpatient follow-up and clinical outcomes of People Living with HIV (PLHIV) at a specialized infectious diseases clinic in southeastern Brazil. A retrospective analysis was conducted using medical records and responses to a structured questionnaire from PLHIV followed between March 2020 and December 2021. Clinical and laboratory data (CD4 count, viral load, and antiretroviral therapy changes) were reviewed, and questionnaire responses were used to assess COVID-19 history, vaccination, and mental health symptoms. A total of 125 patients were included (mean age 38.6-years; 64.1% male). Prior to the pandemic, 80.3% had CD4 counts > 200 cells/µL and 82.1% had undetectable viral load, increasing to 89.7% and 84.6%, respectively, during the pandemic. Twenty-six patients (22.2%) changed their antiretroviral regimen, mainly due to switching to the nationally recommended first-line therapy. Among the 55 respondents to the questionnaire, 13 (24%) reported confirmed COVID-19 infection; of these, 2 (15.4%) required hospitalization. Overall, 53 (96.4%) reported having received the COVID-19 vaccination. Symptoms of depression and anxiety were reported by 27.7% and 45.4% of participants, respectively. Despite the logistic challenges associated with the COVID-19 pandemic, viral suppression, immunologic recovery, and retention in care remained stable in this selected cohort of patients with continuous follow-up, reflecting the resilience of the healthcare service and sustained treatment adherence.