Validity, reliability, and responsiveness of the Brazilian version of the instrument World Health Organization Disability Assessment Schedule (WHODAS 2.0) for individuals with obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is a disabling health condition, and there is no disease-specific patient-reported outcome instrument to assess individuals with OSA. OBJECTIVES: To evaluate the psychometric properties of the Brazilian version of the World Health Organization Disability Assessment Schedule (WHODAS 2.0) in individuals with OSA. METHODS: One hundred individuals with OSA responded to the WHODAS 2.0 version of 36 items, the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), and the 12-item health survey (SF-12). Internal consistency, convergent and discriminative validity, and responsiveness to continuous positive airway pressure (CPAP) were the psychometric properties tested. RESULTS: Cronbach's α values indicate good internal consistency (0.91 - 0.73), except for the self-care domain (α = 0.52). Convergent validity indicated an excellent correlation (r = -0.80) between the domains of functioning and quality of life. Discriminative validity showed no association between OSA severity and functioning (p = 0.90). The responsiveness to CPAP treatment showed a large effect size (r = 0.82; p < 0.05) CONCLUSIONS: The WHODAS 2.0 instrument is valid, reliable, and responsive for assessing individuals with OSA.

Robotic-assisted cholecystectomy versus conventional laparoscopic cholecystectomy for benign gallbladder disease: a systematic review and meta-analysis.

Laparoscopic cholecystectomy (LC) is the established gold standard treatment for benign gallbladder diseases. However, robotic cholecystectomy is still controversial. Therefore, we aimed to compare intraoperative and postoperative outcomes in LC and robotic-assisted cholecystectomy (RAC) in patients with nonmalignant gallbladder conditions. PubMed, Scopus, Cochrane Library, and Web of Science were systematically searched for studies comparing RAC to LC in patients with benign gallbladder disease. Only randomized trials and non-randomized studies with propensity score matching were included. Mean differences (MDs) were computed for continuous outcomes and odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Heterogeneity was assessed with I2 statistics. Statistical analysis was performed using Software R, version 4.2.3. A total of 13 studies comprising 22,440 patients were included, of whom 10,758 patients (47.94%) underwent RAC. The mean age was 48.5 years and 65.2% were female. Compared with LC, RAC significantly increased operative time (MD 12.59 min; 95% CI 5.62-19.55; p < 0.01; I2 = 79%). However, there were no significant differences between the groups in hospitalization time (MD -0.18 days; 95% CI - 0.43-0.07; p = 0.07; I2 = 89%), occurrence of intraoperative complications (OR 0.66; 95% CI 0.38-1.15; p = 0.14; I2 = 35%) and bile duct injury (OR 0.99; 95% CI 0.64, 1.55; p = 0.97; I2 = 0%). RAC was associated with an increase in operative time compared with LC without increasing hospitalization time or the incidence of intraoperative complications. These findings suggest that RAC is a safe approach to benign gallbladder disease.

ELISA with recombinant antigen Lb6H validated for the diagnosis of American tegumentary leishmaniasis.

American tegumentary leishmaniasis (ATL) diagnosis is an open question, and the search for a solution is urgent. The available tests that detect the etiological agent of the infection are specific for ATL diagnosis. However, they present disadvantages, such as low sensitivity and the need for invasive procedures to obtain the samples. Immunological methods (leishmanin skin test and search for anti-Leishmania antibodies) are good alternatives to the etiological diagnosis of ATL. Presently, we face problems with disease confirmation due to the discontinuity in the production of leishmanin skin test antigen, particularly in resource-poor settings. Aiming to diagnose ATL, we validated rLb6H-ELISA for IgG antibodies using 1,091 samples from leishmaniasis patients and healthy controls, divided into four panels, living in 19 Brazilian endemic and non-endemic states. The rLb6H-ELISA showed a sensitivity of 98.6% and a specificity of 100.0%, with the reference panel comprising 70 ATL patient samples and 70 healthy controls. The reproducibility evaluation showed a coefficient of variation of positive samples ≤ 8.20% for repeatability, ≤ 17,97% for reproducibility, and ≤ 8.12% for homogeneity. The plates sensitized with rLb6H were stable at 4°C and -20°C for 180 days and 37°C for seven days, indicating 12 months of validity. In samples of ATL patients from five research and healthcare centers in endemic and non-endemic areas, rLb6H-ELISA showed a sensitivity of 84.0%; no significant statistical difference was observed among the five centers (chi-square test, p = 0.13). In samples of healthy controls from four areas with different endemicity, a specificity of 92.4% was obtained; lower specificity was obtained in a visceral leishmaniasis high endemicity locality (chi-square test, p<0.001). Cross-reactivity was assessed in 166 other disease samples with a positivity of 13.9%. Based on the good diagnostic performance and the reproducibility and stability of the antigen, we suggest using ELISA-rLb6H to diagnose ATL.

A randomised phase II study of extended pleurectomy/decortication (e-PD) preceded or followed by chemotherapy in patients (pts) with early-stage pleural mesothelioma (PM): EORTC 1205.

BACKGROUND: The role of surgery in pleural mesothelioma remains controversial. It may be appropriate in highly selected patients as part of a multimodality treatment including chemotherapy. Recent years have seen a shift from extrapleural pleuropneumonectomy toward extended pleurectomy/decortication. The most optimal sequence of surgery and chemotherapy remains unknown. METHODS: EORTC-1205-LCG was a multi-centric, non-comparative phase 2 trial, 1:1 randomising between immediate (arm A) and deferred surgery (arm B), followed or preceded by chemotherapy. Eligible patients (ECOG 0-1) had treatment-naïve, borderline resectable T1-3 N0-1 M0 mesothelioma of any histology. Primary outcome was rate of success at 20 weeks, a composite endpoint containing (1) successfully completing both treatments within 20 weeks; (2) being alive with no signs of progressive disease; and (3) no residual grade 3-4 toxicity. Secondary endpoints were toxicity, OS, PFS, and process indicators of surgical quality. FINDINGS: 69 patients were included in this trial. 56 patients (81%) completed 3 cycles of chemotherapy and 58 patients (84%) underwent surgery. Of the 64 patients in the primary analysis, 21/30 patients in arm A (70.0%; 80% CI: 56.8-81.0) and 17/34 patients (50.0%; 80% CI: 37.8-62.2) in arm B reached the statistical endpoint for rate of success. Median progression-free survival and overall survival were 10.8 [95% CI 8.5-17.2] and 27.1 months [95% CI 22.6-64.3] in arm A, and 8.0 [95% CI 7.2-21.9] and 33.8 months [95% CI 23.8-44.6] in arm B. Macroscopic complete resection was obtained in 82.8% of patients. 30- and 90-day mortality were both 1.7%. No new safety signals were found, but treatment-related morbidity was high. INTERPRETATION: EORTC 1205 did not succeed in selecting a preferred sequence of pre- or postoperative chemotherapy. Either procedure is feasible with a low mortality, albeit consistent morbidity. A shared informed decision between surgeon and patient remains essential.

"I Am from the Ghetto, I Am Black, I Live in the Slum and They Think: Why Bother with Her?" - Racism in Seeking Help Experiences for Domestic Violence in Brazil.

Despite the majority of Brazilians identifying as black, racial disparities are significant. Black women encounter disproportionate difficulties, with greater rates of homicide, unemployment, and poverty. After the Maria da Penha Law (2006), which is regarded as one of the most comprehensive laws to address domestic violence, there has been a notable increase in femicide among black women and a decrease in cases among white women. This paper aims to analyze the differences between white and black survivors of domestic violence in terms of the access and support they received from the violence against women multi agency network in the city of São Paulo, Brazil. To this end, in-depth interviews (IDI) were conducted with nine white and nine black women who were seeking help in the justice system in June of 2018. The IDI were analyzed under critical path and structural racism theories, in order to understand how inequality markers such as race might affect the institutional response to the survivor's help seeking. The results indicated that black women received less information and support while seeking institutional help, as they faced more obstacles compared to white women. Among the interviewees critical paths, the access to the services was denied by providers 13 times for black women in contrast with 1 access denial for white women-also considering cases that discontinued the needed assistance due to institutional violence. The observed obstacles lived by black women in the multiagency network not only resulted in the path for these women toward support being longer but in many cases being repeated unsuccessfully multiple times. This study concludes that thus all women face obstacles while seeking help in formal institutions, black women may face greater barriers in this path due to how structural racism is reproduced in the services that should guarantee rights.

Comparison between melatonin versus melatonin and photobiomodulation versus photobiomodulation in the treatment of Alopecia X in German Spitz dogs: Clinical, randomized, double-blind, parallel, non-inferiority protocol.

Canine Alopecia X is a non-inflammatory hair loss disorder of unknown etiology that predominantly affects German Spitz dogs. Treatment modalities include hormone and/or melatonin supplementation and low trauma microneedling. Melatonin influences hair growth and pigmentation in several species and presents a low risk of adverse effects when used in dogs with Alopecia X. Photobiomodulation (PBM) is frequently used in human androgenetic alopecia and alopecia areata; despite this, PBM remains unexplored in canine Alopecia X. To address this knowledge gap, sixty dogs of both sexes will be randomly assigned to three groups: (i) melatonin only group (3 mg/Kg, n = 20); (ii) PBM only group (diode laser, wavelength 660nm, 100mw power, with 3 J/point, 2 sessions/week for 3 months, n = 20); (ii) PBM + melatonin group (n = 20). The objective is to determine the potential of PBM alone or in conjunction with melatonin supplementation in promoting hair regrowth (hair density and diameter) by means of dermatoscopy and planimetry over a period of 90 days.

Perspectives of healthcare professionals on training for quantitative G6PD testing during implementation of tafenoquine in Brazil (QualiTRuST Study).

Effective radical cure of Plasmodium vivax malaria is essential for malaria elimination in Brazil. P. vivax radical cure requires administration of a schizonticide, such as chloroquine, plus an 8-aminoquinoline. However, 8-aminoquinolines cause hemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, requiring prior screening to exclude those at risk. Brazil is pioneering the implementation of tafenoquine, a single-dose 8-aminoquinoline indicated for P. vivax patients with >70% of normal G6PD activity. Tafenoquine implementation in Manaus and Porto Velho, two municipalities located in the western Brazilian Amazon, included comprehensive training of healthcare professionals (HCPs) on point-of-care quantitative G6PD testing and a new treatment algorithm for P. vivax radical cure incorporating tafenoquine. Training was initially provided to higher-level facilities (phase one) and later adapted for primary care units (phase two). This study analyzed HCP experiences during training and implementation and identified barriers and facilitators. In-depth interviews and focus discussion groups were conducted 30 days after each training for a purposive random sample of 115 HCPs. Thematic analysis was employed using MAXQDA software, analyzing data through inductive and deductive coding. Analysis showed that following the initial training for higher-level facilities, some HCPs did not feel confident performing quantitative G6PD testing and prescribing the tafenoquine regimen. Modifications to the training in phase two resulted in an improvement in understanding the implementation process of the G6PD test and tafenoquine, as well as in the knowledge acquired by HCPs. Additionally, knowledge gaps were addressed through in situ training, peer communication via a messaging app, and educational materials. Training supported effective deployment of the new tools in Manaus and Porto Velho and increased awareness of the need for pharmacovigilance. A training approach for nationwide implementation of these tools was devised. Implementing quantitative G6PD testing and tafenoquine represents a significant shift in P. vivax malaria case management. Consistent engagement with HCPs is needed to overcome challenges in fully integrating these tools within the Brazilian health system.

What is the role of circRNAs in the pathogenesis of cervical cancer? A systematic literature review.

Cervical Cancer (CC) is one of the most prevalent neoplasms among women, considered the leading cause of gynecological death worldwide, and the fourth most common type of cancer. Regional metastasis is closely related to the low effectiveness of treatment, and validating biomarkers can optimize accuracy in diagnosis and prognosis. Among the potential biomarkers associated with disease metastasis are circular RNAs (circRNAs), whose altered expression has been linked to CC progression. In this context, this systematic review aims to compile information on the clinical-pathological significance and describe the biological function of circRNAs. Inclusion and exclusion criteria were used to include relevant literature, followed by in silico analysis. Additionally, we employed the UALCAN tools to search for host genes of circRNAs and expression data, miRTargetLink 2.0 to predict interactions of microRNA target genes and the Cytoscape software to predict possible interactions of microRNA target genes. According to the research, most circRNAs were found to be overexpressed and described as regulators of processes such as invasion, cell proliferation, apoptosis and migration. They were also implicated in clinical significance, including metastasis, TNM staging and microRNA interactions. CircRNAs may participate in critical processes in tumorigenesis; therefore, understanding the underlying molecular mechanisms of gene regulation in CC can contribute to the accuracy of diagnosis, prognosis and therapy.

Comprehensive analysis of gastrointestinal side effects in COVID-19 patients undergoing combined pharmacological treatment with azithromycin and hydroxychloroquine: a systematic review and network meta-analysis.

During the COVID-19 pandemic, several drugs were repositioned and combined to quickly find a way to mitigate the effects of the infection. However, the adverse effects of these combinations on the gastrointestinal tract are unknown. We aimed investigate whether Hydroxychloroquine (HD), Azithromycin (AZ), and Ivermectin (IV) used in combination for the treatment of COVID-19, can lead to the development of gastrointestinal disorders. This is a systematic review and network meta-analysis conducted using Stata and Revman software, respectively. The protocol was registered with PROSPERO (CRD42023372802). A search of clinical trials in Cochrane Library databases, Embase, Web of Science, Lilacs, PubMed, Scopus and Clinicaltrials.gov conducted on November 26, 2023. The eligibility of the studies was assessed based on PICO criteria, including trials that compared different treatments and control group. The analysis of the quality of the evidence was carried out according to the GRADE. Six trials involving 1,686 COVID-19 patients were included. No trials on the association of HD or AZ with IV met the inclusion criteria, only studies on the association between HD and AZ were included. Nausea, vomiting, diarrhea, abdominal pain and increased transaminases were related. The symptoms of vomiting and nausea were evaluated through a network meta-analysis, while the symptom of abdominal pain was evaluated through a meta-analysis. No significant associations with these symptoms were observed for HD, AZ, or their combination, compared to control. Low heterogeneity and absence of inconsistency in indirect and direct comparisons were noted. Limitations included small sample sizes, varied drug dosages, and potential publication bias during the pandemic peak. This review unveils that there are no associations between gastrointestinal adverse effects and the combined treatment of HD with AZ in the management of COVID-19, as compared to either the use of a control group or the administration of the drugs individually, on the other hand, highlighting the very low or low certainty of evidence for the evaluated outcomes. To accurately conclude the absence of side effects, further high-quality randomized studies are needed.

Polycyclic aromatic hydrocarbons in seawater after the mysterious oil spill of 2019 on the Pernambuco coast, northeast Brazil.

In 2019, one of Brazil's most significant environmental disasters occurred, involving an oil spill that directly affected Pernambuco state. Contamination along the coast was evaluated by the quantification of polycyclic aromatic hydrocarbons (PAHs) in fifty seawater samples collected in the summer and winter of 2021. Analysis using fluorescence spectroscopy revealed that for all the samples, levels of dissolved/dispersed petroleum hydrocarbons (DDPHs) were higher than the regional baseline for tropical western shores of the Atlantic Ocean. GC-MS analyses quantified 17 PAHs in the samples, with highest total PAHs concentrations of 234 ng L-1 in summer and 33.3 ng L-1 in winter, which were consistent with the highest risks observed in ecotoxicity assays. The use of diagnostic ratios showed that the coast was impacted by a mixture of PAHs from petrogenic and pyrolytic sources. The results indicated the need for continuous monitoring of the regions affected by the 2019 spill.

Burden of liver disease in Brazil, 1996-2022: a retrospective descriptive study of the epidemiology and impact on public healthcare.

Background: Liver disease is a major cause of mortality and morbidity worldwide and its epidemiology depends on the genetic background, exposure to risk factors, access to healthcare and other sociodemographic characteristics. Brazil is a large country with diverse multicultural and ethnic heritages and important socioeconomic inequalities. The burden of liver disease in Brazil, its regions and population is unknown. Methods: We retrieved data from the Unified Health System regarding liver diseases and analyzed the mortality and morbidity from 1996 to 2022 by gender, race/ethnicity, age, region and overall. We calculated the age-specific risk of deaths by liver disease, age-standardization of the data, mean hospitalization and liver transplant-associated costs. Findings: Malignant neoplasm of the liver and intrahepatic bile ducts, alcohol-associated liver disease, fibrosis, and cirrhosis of the liver, other diseases of the liver, hepatic failure, chronic viral hepatitis were identified as the major causes of death and morbidity in Brazil in the period analyzed. The epidemiology of these diseases was diverse, with variations according to geographic regions, gender and race/ethnicity. The major economic burden of liver disease is related to liver transplants, a common outcome of the progression of these diseases. Interpretation: Liver disease in Brazil is a serious issue for the public health system due to the high number of deaths and increasing mortality rate. Our study contributes as a necessary prerequisite for the development of tailored public health policies aimed at mitigating the increasing burden of liver diseases in specific populations and regions. Funding: CNPq, INCT, CAPES, FAPEMIG.

Effect of antihypertensive agents on sleep apnea and ambulatory blood pressure in patients with hypertension: A randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) and hypertension are common conditions that may be linked through sympathetic activation and water retention. We hypothesized that diuretics, which reduce the body water content, may be more effective than amlodipine, a blood pressure (BP)-lowering agent implicated with edema, in controlling OSA in patients with hypertension. We also aimed to compare the effects of these treatments on ambulatory blood pressure monitoring (ABPM). METHODS: In a randomized, double-blind clinical trial, we compared the effects of chlorthalidone/amiloride 25/5 mg with amlodipine 10 mg on OSA measured by portable sleep monitor and BP measured by ABPM. The study included participants older than 40 who had moderate OSA (10-40 apneas/hour of sleep) and BP within the systolic range of 140-159 mmHg or diastolic range of 90-99 mmHg. RESULTS: The individuals in the experimental groups were comparable in age, gender, and other relevant characteristics. Neither the combination of diuretics nor amlodipine alone reduced the AHI after 8 weeks of treatment (AHI 26.3 with diuretics and 25.0 with amlodipine. P = 0.713). Both treatments significantly lowered office, 24-h, and nighttime ABP, but the two groups had no significant difference. CONCLUSION: Chlorthalidone associated with amiloride and amlodipine are ineffective in decreasing the frequency of sleep apnea episodes in patients with moderate OSA and hypertension. Both treatments have comparable effects in lowering both office and ambulatory blood pressure. The notion that treatments could offer benefits for both OSA and hypertension remains to be demonstrated. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT01896661.

Dental Profile of Brazilian Patients with Rare Skeletal Genetic Disorders: Clinical Features and Associated Factors.

The aim of this study is to compare the dental profiles of Brazilian patients with rare genetic skeletal disorders and normotypical patients. A cross-sectional study was carried out with 210 individuals aged between 2 and 54 years old [105 with rare diseases (Mucopolysaccharidosis/MPS n = 27 and Osteogenesis Imperfecta/OI n = 78) and 105 without rare diseases] and their parents/caregivers. The parents/caregivers answered a questionnaire about individual aspects of their child and the dental profile was identified from questions related to dental history and the presence/absence of dental problems. The patients' oral cavity was also examined by three examiners for dental caries, malocclusion, gingivitis, and dental anomalies. The average age of individuals with a rare disease was 14.1 years (±12.2) and the median was 9.5 years. Participants who had already used the public health system (SUS) dental care services had a 2.24 times higher chance of belonging to the group with a rare disease (OR = 2.24; 95% CI: 1.07-4.89). Patients with rare diseases are 14.86 times more likely to have difficulty receiving dental treatment (OR = 14.86; 95% CI: 5.96-27.03) and 10.38 times more likely to have one or more dental problems (OR = 10.38; 95% CI: 1.95-35.17). Individuals with rare disorders have a greater history of difficulty in accessing dental treatment, using the SUS, and were diagnosed with more dental problems compared to normotypical individuals.

Photobiomodulation mitigates Bothrops jararacussu venom-induced damage in myoblast cells by enhancing myogenic factors and reducing cytokine production.

BACKGROUND: Photobiomodulation has exhibited promise in mitigating the local effects induced by Bothrops snakebite envenoming; however, the mechanisms underlying this protection are not yet fully understood. Herein, the effectiveness of photobiomodulation effects on regenerative response of C2C12 myoblast cells following exposure to Bothrops jararacussu venom (BjsuV), as well as the mechanisms involved was investigated. METHODOLOGY/PRINCIPAL FINDINGS: C2C12 myoblast cells were exposed to BjsuV (12.5 µg/mL) and irradiated once for 10 seconds with laser light of 660 nm (14.08 mW; 0.04 cm2; 352 mW/cm2) or 780 nm (17.6 mW; 0.04 cm2; 440 mW/ cm2) to provide energy densities of 3.52 and 4.4 J/cm2, and total energies of 0.1408 and 0.176 J, respectively. Cell migration was assessed through a wound-healing assay. The expression of MAPK p38-α, NF-Кß, Myf5, Pax-7, MyoD, and myogenin proteins were assessed by western blotting analysis. In addition, interleukin IL1-ß, IL-6, TNF-alfa and IL-10 levels were measured in the supernatant by ELISA. The PBM applied to C2C12 cells exposed to BjsuV promoted cell migration, increase the expression of myogenic factors (Pax7, MyF5, MyoD and myogenin), reduced the levels of proinflammatory cytokines, IL1-ß, IL-6, TNF-alfa, and increased the levels of anti-inflammatory cytokine IL-10. In addition, PBM downregulates the expression of NF-kB, and had no effect on p38 MAKP. CONCLUSION/SIGNIFICANCE: These data demonstrated that protection of the muscle cell by PBM seems to be related to the increase of myogenic factors as well as the modulation of inflammatory mediators. PBM therapy may offer a new therapeutic strategy to address the local effects of snakebite envenoming by promoting muscle regeneration and reducing the inflammatory process.

A recombinant chimeric antigen constructed with B-cell epitopes from Mycobacterium leprae hypothetical proteins is effective for the diagnosis of leprosy.

The diagnosis if leprosy is difficult, as it requires clinical expertise and sensitive laboratory tests. In this study, we develop a serological test for leprosy by using bioinformatics tools to identify specific B-cell epitopes from Mycobacterium leprae hypothetical proteins, which were used to construct a recombinant chimeric protein, M1. The synthetic peptides were obtained and showed good reactivity to detect leprosy patients, although the M1 chimera have showed sensitivity (Se) and specificity (Sp) values higher than 90.0% to diagnose both paucibacillary (PB) and multibacillary (MB) leprosy patients, but not those developing tegumentary or visceral leishmaniasis, tuberculosis, Chagas disease, malaria, histoplasmosis and aspergillosis, in ELISA experiments. Using sera from household contacts, values for Se and Sp were 100% and 65.3%, respectively. In conclusion, our proof-of-concept study has generated data that suggest that a new recombinant protein could be developed into a diagnostic antigen for leprosy.

Effect of heatwaves on daily hospital admissions in Portugal, 2000-18: an observational study.

BACKGROUND: Climate change has increased the frequency, intensity, and duration of heatwaves, posing a serious threat to public health. Although the link between high temperatures and premature mortality has been extensively studied, the comprehensive quantification of heatwave effects on morbidity remains underexplored. METHODS: In this observational study, we assessed the relationship between heatwaves and daily hospital admissions at a county level in Portugal. We considered all major diagnostic categories and age groups (<18 years, 18-64 years, and ≥65 years), over a 19-year period from 2000 to 2018, during the extended summer season, defined as May 1, to Sept 30. We did a comprehensive geospatial analysis, integrating over 12 million hospital admission records with heatwave events indexed by the Excess Heat Factor (EHF), covering all 278 mainland counties. We obtained data from the Hospital Morbidity Database and E-OBS daily gridded meteorological data for Europe from 1950 to present derived from in-situ observations. To estimate the effect of heatwaves on hospital admissions, we applied negative binomial regression models at both national and county levels. FINDINGS: We found a statistically significant overall increase in daily hospital admissions during heatwave days (incidence rate ratio 1·189 [95% CI 1·179-1·198]; p<0·0001). All age groups were affected, with children younger than 18 years being the most affected (21·7% [20·6-22·7] increase in admissions; p<0·0001), followed by the working-age (19·7% [18·7-20·7]; p<0·0001) and elderly individuals (17·2% [16·2-18·2]; p<0·0001). All 25 major disease diagnostic categories showed significant increases in hospital admissions, particularly burns (34·3% [28·7-40·1]; p<0·0001), multiple significant trauma (26·8% [22·2-31·6]; p<0·0001), and infectious and parasitic diseases (25·4% [23·5-27·3]; p<0·0001). We also found notable increases in endocrine, nutritional, and metabolic diseases (25·1% [23·4-26·8]; p<0·0001), mental diseases and disorders (23·0% [21·1-24·8]; p<0·0001), respiratory diseases (22·4% [21·2-23·6]; p<0·0001), and circulatory system disorders (15·8% [14·7-16·9]; p<0·0001). INTERPRETATION: Our results provide statistically significant evidence of the association between heatwaves and increased hospitalisations across all age groups and for all major causes of disease. To our knowledge, this is the first study to estimate the full extent of heatwaves' impact on hospitalisations using the EHF index over a 19-year period, encompassing an entire country, and spanning 25 disease categories during multiple heatwave events. Our data offer crucial information to guide policy makers in effectively and efficiently allocating resources to address the profound health-care consequences resulting from climate change. FUNDING: None.

Current knowledge on leptospirosis in cats: A systematic review with metanalysis on direct detection, serological response, and clinical data.

Leptospirosis is a neglected bacterial zoonosis that affects a wide range of mammals, with important implications from a One Health perspective. Over the past years feline leptospirosis has gained increased attention in the scientific community. Here we describe a systematic review with meta-analysis that followed the PRISMA guidelines, with an additional PROSPERO registration. The study provides global seropositivity, urinary shedding rates, global serogroup distribution, descriptive data of leptospires that had been isolated from cats and clinical and laboratory features presented by symptomatic cats with acute disease. The search was carried out in six different databases, with the identification of 79 reports describing leptospiral infection in cats. The pooled frequency of seroreactive cats was 11% (95% CI: 9%-13%), with Javanica and Pomona as the most frequent serogroups found. Frequency for urinary shedding was 8% (95% CI: 5%-10%), with L. interrogans identified in most samples. A total of 16 isolates were isolated from cats, with Bataviae as the most frequent serogroup. Twenty symptomatic cats with confirmed leptospiral infection were identified. Anorexia, lethargy, polydipsia, and bleeding disorders were the clinical signs most frequently reported. The results suggest that cats from some locations are exposed to leptospires and may act as urinary shedders of this pathogen, thus indicating a possible role of this species in disease transmission. Clinical data indicates that acute infection is mostly atypical when compared to dogs, and due to difficulties to define an archetypal clinical presentation in cats, feline leptospirosis is likely to be underdiagnosed disease in this species.

Comparing health systems readiness for integrating domestic violence services in Brazil, occupied Palestinian Territories, Nepal and Sri Lanka.

Domestic violence (DV) is a global prevalent health problem leading to adverse health consequences, yet health systems are often unprepared to address it. This article presents a comparative synthesis of the health system's pre-conditions necessary to enable integration of DV in health services in Brazil, Nepal, Sri Lanka and occupied Palestinian Territories (oPT). A cross-country, comparative analysis was conducted using a health systems readiness framework. Data collection involved multiple data sources, including qualitative interviews with various stakeholders; focus-group discussions with women; structured facility observations; and a survey with providers. Our findings highlight deficiencies in policy and practice that need to be addressed for an effective DV response. Common readiness gaps include unclear and limited guidance on DV, unsupportive leadership coupled with limited training and resources. Most providers felt unprepared, lacked guidance and felt unsupported and unprotected by managers and their health system. While in Brazil most providers felt they should respond to DV cases, many in Sri Lanka preferred not to. Such organizational and service delivery challenges, in turn, also affected how health providers responded to DV cases leaving them not confident, uncertain about their knowledge and unsure about their role. Furthermore, providers' personal beliefs and values on DV and gender norms also impacted their motivation and ability to respond, prompting some to become 'activists' while others were reluctant to intervene and prone to blame women. Our synthesis also pointed to a gap in women's use of health services for DV as they had low trust in providers. Our conceptual framework demonstrates the importance of having clear policies and highlights the need to engage leadership across every level of the system to reframe challenges and strengthen routine practices. Future research should also determine the ways in which women's understanding and needs related to DV help-seeking are addressed.

Structural characterization of amyloid aggregates with spatially resolved infrared spectroscopy.

The self-assembly of proteins and peptides into ordered structures called amyloid fibrils is a hallmark of numerous diseases, impacting the brain, heart, and other organs. The structure of amyloid aggregates is central to their function and thus has been extensively studied. However, the structural heterogeneities between aggregates as they evolve throughout the aggregation pathway are still not well understood. Conventional biophysical spectroscopic methods are bulk techniques and only report on the average structural parameters. Understanding the structure of individual aggregate species in a heterogeneous ensemble necessitates spatial resolution on the length scale of the aggregates. Recent technological advances have led to augmentation of infrared (IR) spectroscopy with imaging modalities, wherein the photothermal response of the sample upon vibrational excitation is leveraged to provide spatial resolution beyond the diffraction limit. These combined approaches are ideally suited to map out the structural heterogeneity of amyloid ensembles. AFM-IR, which integrates IR spectroscopy with atomic force microscopy enables identification of the structural facets the oligomers and fibrils at individual aggregate level with nanoscale resolution. These capabilities can be extended to chemical mapping in diseased tissue specimens with submicron resolution using optical photothermal microscopy, which combines IR spectroscopy with optical imaging. This book chapter provides the basic premise of these novel techniques and provides the typical methodology for using these approaches for amyloid structure determination. Detailed procedures pertaining to sample preparation and data acquisition and analysis are discussed and the aggregation of the amyloid ß peptide is provided as a case study to provide the reader the experimental parameters necessary to use these techniques to complement their research efforts.

Prioritization criteria in policies and management of human resources for health: a proposal for a validated methodology.

Objective: To create and validate criteria for prioritizing problems related to policies and management of the health workforce. Methods: This methodological study was divided into three stages. First, the criteria were elaborated by means of a systematized literature review. Second, the criteria were evaluated online by a committee of judges comprised of eight specialists. In the third stage, an evaluation was carried out by the target audience in a hybrid workshop. The participants evaluated the material using the Suitability Assessment of Materials instrument, adapted for the research. Results: Three prioritization criteria (relevance, window of opportunity and acceptability) and a scoring scale were developed based on the literature review. In the evaluation by the committee of judges, the approval percentage of the criteria and prioritization method was 84%. Modifications were made based on suggestions in relation to the material presented to the specialists. In the pre-test stage, the approval percentage varied by item, with six of them reaching a maximum approval of 100% (corresponding to approximately 46% of the items), four reaching 92% and three achieving 83% each, indicating positive results. Conclusions: The developed criteria were considered valid for use in the context of policies and management in the area of human resources for health.