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Leptospirosis is a global health concern, particularly in tropical regions, with clinical symptoms varying from mild fever to severe organ dysfunction. We present a case of a 57-year-old male with septic shock and acute kidney injury due to acute leptospirosis. The patient's rapid progression to shock within a day of generalized symptoms was unusual. The patient's infection ultimately resolved with ceftriaxone and he was discharged after 14 days of therapy. The pathogenesis of severe leptospirosis is believed to be due to vasculitis, with organ damage caused by the leptospira bacteria and immune-mediated mechanisms. Diagnostic investigations include blood cultures and polymerase chain reactions, which are beneficial for early diagnosis. The management of patients depends on the severity of symptoms and other health conditions, as well as antibiotics and hydration. However, leptospirosis can lead to a wide range of complications, including neurological, ocular, hematological, and gastrointestinal involvement, necessitating vigilant monitoring and management.
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BACKGROUND: Physical activity engagement following a cancer diagnosis is positively associated with survival, reduced risk of disease recurrence, and reduced cancer-specific and all-cause mortality. However, rates of physical activity engagement are low among individuals diagnosed with and being treated for breast cancer or prostate cancer. OBJECTIVE: The purpose of this study was to describe the systematic process of developing an e-cycling intervention aimed at increasing physical activity among individuals living with prostate cancer or breast cancer and outline the key components to be implemented. METHODS: The Medical Research Council guidance for developing complex interventions and the Behaviour Change Wheel were used to guide intervention development. Information was gathered from the literature and through discussions with end users to understand factors influencing e-cycling. These factors were mapped onto the Theoretical Domains Framework to identify potential mechanisms of action. Behavior change techniques were selected from theory and evidence to develop intervention content. Interested parties, including cycling instructors, end users, and behavior change experts, reviewed and refined the intervention. RESULTS: Anticipated barriers and facilitators to e-cycling engagement were mapped onto 11 of the 14 domains of the Theoretical Domains Framework. A total of 23 behavior change techniques were selected to target these domains over 4 one-to-one e-cycling sessions delivered by trained cycling instructors in the community. Cycling instructors were provided a 3-hour classroom training session on delivering the intervention and a 3-hour practical session with feedback. The outcome of this work is a theory and evidence-informed intervention aimed at promoting e-cycling behavior among individuals being treated for breast cancer or prostate cancer, which is currently being implemented and evaluated. CONCLUSIONS: Transparent intervention development and reporting of content is important for comprehensively examining intervention implementation. The implementation of this intervention package is currently being evaluated in a pilot randomized controlled trial. If the intervention is found to be effective and the content and delivery are acceptable, this intervention will form a basis for the development of e-cycling interventions in other survivors of cancer. TRIAL REGISTRATION: ISRCTN Registry ISRCTN39112034 https://www.isrctn.com/ISRCTN39112034; and IRSCTN Registry ISRCTN42852156; https://www.isrctn.com/ISRCTN42852156.
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Histopathology is a challenging interpretive discipline, and the level of confidence a pathologist has in their diagnosis is known to vary, which is conveyed descriptively in pathology reports. There has been little study to accurately quantify pathologists' diagnostic confidence or the factors that influence it. In this study involving sixteen pathologists from six NHS trusts, we assessed diagnostic confidence across multiple variables and four specialties. Each case was reported by four pathologists, with each pathologist reporting each case twice (on light microscopy (LM) and digital pathology (DP)). For each diagnosis, pathologists recorded their confidence on a 7-point Likert scale. This provided 16,187 diagnoses and associated confidence scores for analysis. All variables investigated were found to be significantly predictive of diagnostic confidence, except level of pathologist experience. Confidence was lower for difficult to report cases, cases where there was inter- and intra-pathologist variation in the diagnosis, and cases where the pathologist made an incorrect diagnosis. Confidence was higher, although nominally, for LM diagnoses than DP (rate ratio 1.09 (95% CI 1.01-1.18), p = 0.035), although results indicate pathologists are confident to report on DP. Lowest confidence scores were seen in areas of known diagnostic complexity and cases with quality issues. High confidence in incorrect diagnoses were almost invariably attributed to interpretive diagnostic differences which occurred across both rare and common lesions. The results highlight the value of external quality control schemes and the benefits of selective peer review when reporting.
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There is a knowledge gap on the epidemiology of inflammatory bowel disease in Africa. To begin to address this issue we formed a case reporting network of practitioners with an interest in inflammatory bowel disease across sub-Saharan Africa. Here we report a series of 175 cases from 12 countries over 2 years.
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Citrobacter infections have emerged as now a common nosocomial pathogen. Most of the infections manifest in patients with underlying medical conditions. The features of infection can range from infections in the lower urinary tract, respiratory tract, gastrointestinal disease, or bacteremia, however renal abscesses remain uncommon. Here we present the case of a 48-year-old female with medical history of diabetes that presented with a right renal abscess secondary to Citrobacter koseri infection managed with drainage and antimicrobial treatment.
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BACKGROUND: Frailty, a state of increased vulnerability to adverse health outcomes, has garnered significant attention in research and clinical practice. Existing constructs aggregate clinical features or health deficits into a single score. While simple and interpretable, this approach may overlook the complexity of frailty and not capture the full range of variation between individuals. METHODS: Exploratory factor analysis was used to infer latent dimensions of a frailty index constructed using survey data from the English Longitudinal Study of Ageing, wave 9. The dataset included 58 self-reported health deficits in a representative sample of community-dwelling adults aged 65+ (N=4971). Deficits encompassed chronic disease, general health status, mobility, independence with activities of daily living, psychological well-being, memory and cognition. Multiple linear regression examined associations with CASP-19 quality of life scores. RESULTS: Factor analysis revealed four frailty subdimensions. Based on the component deficits with the highest loading values, these factors were labelled 'mobility impairment and physical morbidity', 'difficulties in daily activities', 'mental health' and 'disorientation in time'. The four subdimensions were a better predictor of quality of life than frailty index scores. CONCLUSIONS: Distinct subdimensions of frailty can be identified from standard index scores. A decomposed approach to understanding frailty has a potential to provide a more nuanced understanding of an individual's state of health across multiple deficits.
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In this study, we investigate the expression of muscle markers, including the specific skeletal muscle markers myogenin and myoD1, in neuroendocrine carcinomas (NECs). The study included 23 NECs from various sites (14 small cell NECs and 9 large cell NECs). These were stained with desmin, myogenin and myoD1. Positive staining with at least one muscle marker was observed in 14 cases (61%). 8 (35%), 8 (35%) and 11 (48%) of the cases were positive with desmin, myogenin and myoD1 respectively. In most, but not all, cases positive staining was focal generally involving < 10% of tumour cells. Expression of muscle markers is not uncommon in NECs. This represents an important diagnostic pitfall of which pathologists should be aware. In reporting this phenomenon, we speculate on the pathogenesis of this "aberrant" expression of muscle markers.
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Environmental enteric dysfunction (EED) is a subclinical enteropathy challenging to diagnose due to an overlap of tissue features with other inflammatory enteropathies. EED subjects (n = 52) from Pakistan, controls (n = 25), and a validation EED cohort (n = 30) from Zambia were used to develop a machine-learning-based image analysis classification model. We extracted histologic feature representations from the Pakistan EED model and correlated them to transcriptomics and clinical biomarkers. In-silico metabolic network modeling was used to characterize alterations in metabolic flux between EED and controls and validated using untargeted lipidomics. Genes encoding beta-ureidopropionase, CYP4F3, and epoxide hydrolase 1 correlated to numerous tissue feature representations. Fatty acid and glycerophospholipid metabolism-related reactions showed altered flux. Increased phosphatidylcholine, lysophosphatidylcholine (LPC), and ether-linked LPCs, and decreased ester-linked LPCs were observed in the duodenal lipidome of Pakistan EED subjects, while plasma levels of glycine-conjugated bile acids were significantly increased. Together, these findings elucidate a multi-omic signature of EED.
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Prevention of sports injury and illness and protection of athlete health are key mandates of the IOC. Methodological limitations in Olympic Games surveillance and retired Olympian studies mean there are gaps in the available evidence on Olympian health and the varied challenges occurring at different stages throughout an athlete's career. This (protocol) paper describes the methods for implementation of the IOC Olympian Health Cohort. The study aims to establish a longitudinal cohort of current Olympians and follow them prospectively (around 15 years) throughout their Olympic careers and retirement. The study will use participants who have completed self-report questionnaires. Olympians will be recruited after each Summer and Winter Olympic Games, and all National Olympic Committee (NOC) athletes aged 16 years or older are eligible. The first phase included the Tokyo 2020/2021 and Beijing 2022 Olympians, with the study promoted via IOC platforms, Athlete365 and NOCs. Questionnaires include baseline demographics, sports exposure and history of injuries and illnesses impacting the athlete's ability to continue to train and/or compete for at least 2 weeks. Questions also address retirement from sports, musculoskeletal, mental and general health, and quality of life measures. This protocol describes the methods for the 15-year global IOC Olympian Health Cohort Study, from participant recruitment to the development and distribution of the study questionnaire. This protocol will be updated to report future changes in the study's conduct or questionnaire content. These data will help identify risk factors and inform risk-reduction strategies. The ultimate goal is to protect the health of all athletes during their careers and retirement.
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Elite student-athletes (SAs) in higher education (HE) have distinct mental health (MH) risks. The COVID-19 pandemic put pressure on systems and increased elite SA vulnerability to adverse MH outcomes. The aim of this study was to explore the provision and management of MH in elite HE sports settings during the time of COVID-19 pandemic stress. The secondary aim was to identify lessons and opportunities to enhance future mental healthcare systems and services for elite SAs. A qualitative study design was used to investigate the views of three groups (athletic directors, coaches and sport healthcare providers). Ten key leaders were purposively recruited from HE institutions in Canada, the USA and the United Kingdom. They represented various universities from the National College Athletic Association, U SPORTS Canada and British Universities and Colleges Sport. Semistructured interviews were conducted, recorded, transcribed and thematically analysed. Five key themes were identified: (1) The pandemic disruption had salient impacts on motivation and how elite SAs engaged with sport (2) when student sport systems are under pressure, support staff perceive a change in duties and experience their own MH challenges, (3) the pandemic increased awareness about MH care provision and exposed systemic challenges, (4) digital transformation in MH is complex and has additional challenges for SAs and (5) there were some positive outcomes of the pandemic, lessons learnt and a resulting motivation for systems change. Participants highlighted future opportunities for MH provision in elite university sport settings. Four recommendations were generated from the results.
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BACKGROUND: Helicobacter pylori (H. pylori) is a common bacterial infection which predominately drives upper gastrointestinal pathology. We carried out a nationwide serological survey in response to the deficiency of robust African data on H. pylori prevalence, age of acquisition, socio-geographic determinants, and impact on gastric physiology. MATERIALS AND METHODS: This was a cross-sectional study of archival plasma samples collected during the Zambia Population-based HIV impact Assessment (ZAMPHIA) 2016 survey. ZAMPHIA used a two-stage door-to-door stratified cluster sample approach to collect samples from adults and children from age 0 to 59 years (n = 24,266). We randomly retrieved one fifth of these samples from each of Zambia's 10 provinces and used ELISA to test for H. pylori IgG antibodies, pepsinogen 1 and 2 and gastrin-17. A pepsinogen 1:2 ratio of <3 was used to define gastric atrophy. RESULTS: The analysis of 4050 plasma samples (30% <16 years, 53% females) revealed an overall H. pylori seroprevalence of 79%. By the age of 10 years, more than 75% of the children had H. pylori. Urban residence was associated with increased odds (OR 1.8, 95% CI 1.5-2.2, p < 0.001) and HIV infection was associated with reduced odds (OR 0.7, 95% CI 0.5-0.9, p = 0.02) of H. pylori seropositivity. Gastric atrophy was detected in 6% of H. pylori seropositive adults below 45 years of age and 9% in those between 45 and 59 years. CONCLUSIONS: We have confirmed a high prevalence of H. pylori seropositivity in Zambia, predominantly in urban settings. The prevalence of gastric atrophy is broadly consistent with other populations around the globe, but our sample did not include adults over 60 years.
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Anticorpos Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Humanos , Zâmbia/epidemiologia , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Feminino , Masculino , Adulto , Estudos Transversais , Adolescente , Pessoa de Meia-Idade , Adulto Jovem , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/imunologia , Criança , Pré-Escolar , Anticorpos Antibacterianos/sangue , Estudos Soroepidemiológicos , Lactente , Prevalência , Recém-Nascido , Imunoglobulina G/sangue , Gastrite Atrófica/epidemiologia , Gastrite Atrófica/microbiologiaRESUMO
PURPOSE: It is well established that, together with a multitude of other adverse effects on health, severe obstructive sleep apnoea causes reduced cerebral perfusion and, in turn, reduced cerebral function. Less clear is the impact of moderate obstructive sleep apnoea (OSA). Our aim was to determine if cerebral blood flow is impaired in people diagnosed with moderate OSA. METHODS: Twenty-four patients diagnosed with moderate OSA (15 ≤ apnoea-hypopnea index (AHI) < 30) were recruited (aged 32-72, median 59 years, 10 female). Seven controls (aged 42-73 years, median 62 years, 4 female) with an AHI < 5 were also recruited. The OSA status of all participants was confirmed at baseline by unattended polysomnography and they had an MRI arterial-spin-labelling scan of cerebral perfusion. RESULTS: Neither global perfusion nor voxel-wise perfusion differed significantly between the moderate-OSA and control groups. We also compared the average perfusion across three regional clusters, which had been found in a previous study to have significant perfusion differences with moderate-severe OSA versus control, and found no significant difference in perfusion between the two groups. The perfusions were also very close, with means of 50.2 and 51.8 mL/100 g/min for the moderate-OSAs and controls, respectively, with a negligible effect size (Cohen's d = 0.10). CONCLUSION: We conclude that cerebral perfusion is not impaired in people with moderate OSA and that cerebral flow regulatory mechanisms can cope with the adverse effects which occur in moderate OSA. This is an important factor in clinical decisions for prescription of continuous positive airway pressure therapy (CPAP).
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Circulação Cerebrovascular , Polissonografia , Apneia Obstrutiva do Sono , Vigília , Humanos , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/terapia , Feminino , Pessoa de Meia-Idade , Masculino , Adulto , Idoso , Circulação Cerebrovascular/fisiologia , Vigília/fisiologia , Imageamento por Ressonância Magnética , Valores de Referência , Encéfalo/fisiopatologia , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagemRESUMO
INTRODUCTION: There are uncertainties surrounding the spectrum of upper gastrointestinal (UGI) diseases in sub-Saharan Africa. This is mainly due to the limitations of data collection and recording. We previously reported an audit of UGI endoscopic diagnoses in Zambia spanning from 1977 to 2014. We now have extended this analysis to include subsequent years, in order to provide a more comprehensive picture of how the diagnoses have evolved over 4 decades. METHODS: We combined data collected from the endoscopy unit at the University Teaching Hospital (UTH) in Lusaka during a previous review with that collected from the beginning of 2015 to the end of 2021. Since 2015, an electronic data base of endoscopy reports at the UTH was kept. The electronic data base was composed of drop-down menus that allowed for standardised reporting of findings. Collected data were coded by two experienced endoscopists and analysed. RESULTS: In total, the analysis included 25,849 endoscopic records covering 43 years. The number of endoscopic procedures performed per year increased drastically in 2010. With the exception of the last 2 years, the proportion of normal endoscopies also increased during the time under review. In total, the number of gastric cancer (GC) cases was 658 (3%) while that of oesophageal cancer (OC) was 1168 (5%). The number of GC and OC diagnoses increased significantly over the period under review, (p < 0.001 for both). For OC the increase remained significant when analysed as a percentage of all procedures performed (p < 0.001). Gastric ulcers (GU) were diagnosed in 2095 (8%) cases, duodenal ulcers (DU) in 2276 (9%) cases and 239 (1%) had both ulcer types. DU diagnosis showed a significantly decreasing trend over each decade (p < 0.001) while GU followed an increasing trend (p < 0.001). CONCLUSIONS: UGI endoscopic findings in Lusaka, Zambia, have evolved over the past four decades with a significant increase of OC and GU diagnoses. Reasons for these observations are yet to be established.
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Úlcera Duodenal , Neoplasias Esofágicas , Neoplasias Gástricas , Úlcera Gástrica , Humanos , Estudos Retrospectivos , Zâmbia/epidemiologia , Úlcera Gástrica/diagnóstico , Neoplasias Esofágicas/diagnóstico , Endoscopia Gastrointestinal , Neoplasias Gástricas/diagnóstico por imagemRESUMO
BACKGROUND: Several reviews have examined the health benefits of participation in specific sports, such as baseball, cricket, cross-country skiing, cycling, downhill skiing, football, golf, judo, rugby, running and swimming. However, new primary studies on the topic have recently been published, and the respective meta-analytic evidence needs to be updated. OBJECTIVES: To systematically review, summarise and appraise evidence on physical health benefits of participation in different recreational sports. METHODS: Searches for journal articles were conducted in PubMed/MEDLINE, Scopus, SpoLit, SPORTDiscus, Sports Medicine & Education Index and Web of Science. We included longitudinal and intervention studies investigating physical health outcomes associated with participation in a given sport among generally healthy adults without disability. RESULTS: A total of 136 papers from 76 studies conducted among 2.6 million participants were included in the review. Our meta-analyses of available evidence found that: (1) cycling reduces the risk of coronary heart disease by 16% (pooled hazard ratio [HR] = 0.84; 95% confidence interval [CI]: 0.80, 0.89), all-cause mortality by 21% (HR = 0.79; 95% CI: 0.73, 0.84), cancer mortality by 10% (HR = 0.90; 95% CI: 0.85, 0.96) and cardiovascular mortality by 20% (HR = 0.80; 95% CI: 0.74, 0.86); (2) football has favourable effects on body composition, blood lipids, fasting blood glucose, blood pressure, cardiovascular function at rest, cardiorespiratory fitness and bone strength (p < 0.050); (3) handball has favourable effects on body composition and cardiorespiratory fitness (p < 0.050); (4) running reduces the risk of all-cause mortality by 23% (HR = 0.77; 95% CI: 0.70, 0.85), cancer mortality by 20% (HR = 0.80; 95% CI: 0.72, 0.89) and cardiovascular mortality by 27% (HR = 0.73; 95% CI: 0.57, 0.94) and improves body composition, cardiovascular function at rest and cardiorespiratory fitness (p < 0.010); and (5) swimming reduces the risk of all-cause mortality by 24% (HR = 0.76; 95% CI: 0.63, 0.92) and improves body composition and blood lipids (p < 0.010). CONCLUSIONS: A range of physical health benefits are associated with participation in recreational cycling, football, handball, running and swimming. More studies are needed to enable meta-analyses of health benefits of participation in other sports. PROSPERO registration number CRD42021234839.
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Children who are HIV-exposed but uninfected have increased infectious mortality compared to HIV-unexposed children, raising the possibility of immune abnormalities following exposure to maternal viraemia, immune dysfunction, and co-infections during pregnancy. In a secondary analysis of the SHINE trial in rural Zimbabwe we explored biological pathways underlying infant mortality, and maternal factors shaping immune development in HIV-exposed uninfected infants. Maternal inflammation and cytomegalovirus viraemia were independently associated with infant deaths: mortality doubled for each log10 rise in maternal C-reactive protein (adjusted hazard ratio (aHR) 2.09; 95% CI 1.33-3.27), and increased 1.6-fold for each log10 rise in maternal cytomegalovirus viral load (aHR 1.62; 95% CI 1.11-2.36). In girls, mortality was more strongly associated with maternal C-reactive protein than cytomegalovirus; in boys, mortality was more strongly associated with cytomegalovirus than C-reactive protein. At age one month, HIV-exposed uninfected infants had a distinct immune milieu, characterised by raised soluble CD14 and an altered CD8 + T-cell compartment. Alterations in immunophenotype and systemic inflammation were generally greater in boys than girls. Collectively, these findings show how the pregnancy immune environment in women with HIV underlies mortality and immune development in their offspring in a sex-differentiated manner, and highlights potential new intervention strategies to transform outcomes of HIV-exposed children. ClinicalTrials.gov/NCT01824940.
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Infecções por Citomegalovirus , Infecções por HIV , Complicações Infecciosas na Gravidez , Lactente , Masculino , Gravidez , Criança , Humanos , Feminino , Citomegalovirus , Viremia , Proteína C-Reativa , Inflamação/complicaçõesRESUMO
BACKGROUND: Environmental enteric dysfunction (EED), a chronic inflammatory condition of the small intestine, is an important driver of childhood malnutrition globally. Quantifying intestinal morphology in EED allows for exploration of its association with functional and disease outcomes. OBJECTIVE: We sought to define morphometric characteristics of childhood EED and determine whether morphology features were associated with disease pathophysiology. METHODS: Morphometric measurements and histology were assessed on duodenal biopsy slides for this cross-sectional study from children with EED in Bangladesh, Pakistan, and Zambia (n=69), and those with no pathologic abnormality (NPA; n=8) or celiac disease (n=18) in North America. Immunohistochemistry was also conducted on 46, 8, and 18 biopsy slides, respectively. Linear mixed-effects regression models were used to reveal morphometric differences between EED compared to NPA or celiac disease, and identify associations between morphometry and histology or immunohistochemistry amongst children with EED. RESULTS: In duodenal biopsies, median EED villus height (248 µm), crypt depth (299 µm), and villus:crypt (V:C) ratio (0.9) values ranged between those of NPA (396 µm villus height; 246 µm crypt depth; 1.6 V:C ratio) and celiac disease (208 µm villus height; 365 µm crypt depth; 0.5 V:C ratio). Among EED biopsy slides, morphometric assessments were not associated with histologic parameters or immunohistochemical markers, other than pathologist determined subjective semi-quantitative villus architecture. CONCLUSIONS: Morphometric analysis of duodenal biopsy slides across geographies identified morphologic features of EED, specifically short villi, elongated crypts, and a smaller V:C ratio relative to NPA slides; although not as severe as in celiac slides. Morphometry did not explain other EED features, suggesting that EED histopathologic processes may be operating independently of morphology. While acknowledging the challenges with obtaining relevant tissue, these data form the basis for further assessments of the role of morphometry in EED.
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Latent fingerprints at crime scenes are frequently recovered using forensic gel-lifters, which can help to preserve the crime scene and to enhance visualisation of traces such as blood or paint. In addition to providing fingerprint ridge detail, additional chemical information can also be recovered from gel lifts that may prove pertinent to an investigation. However, while DNA and metal ions have been shown to be able to be detected in gel-lifted fingerprints, the determination of other types of chemical information such as the presence of drugs in gel-lifted prints has not been previously shown. This study demonstrates the application of an ambient ionisation method, sheath flow probe electrospray ionisation-mass spectrometry (sfPESI-MS), to the direct analysis of gel-lifted fingerprints. A model drug compound (zolpidem) is successfully detected from gel-lifted prints from three different surface types: glass, metal, and paper. The surface activity-based separation associated with probe electrospray approaches is shown to resolve zolpidem ions from background phthalate species, significantly enhancing the response obtained from the gel-lifter. A depletion series experiment shows that the drug residue can be detected with up to 100% efficiency after eight consecutive contacts; however, detection efficiency drops to 20% after 30 contacts. The developed approach has potential application to analysis of historical gel-lifters to obtain additional chemical information.
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BACKGROUND: Walking is a key target behavior for promoting population health. This paper charts the 30-year history of walking policy in Scotland. We assess whether population walking levels among adults in Scotland have changed in recent years and identify the characteristics of those least likely to report any walking. METHODS: We pooled 9 years (2012-2019 and 2021) of data from adult (≥16 y) respondents of the Scottish Health Survey (n = 41,470). The outcomes of interest were the percentage reporting (1) any walking and (2) any walking with an average pace that is of at least moderate intensity. We also investigated the contribution of walking to total nonoccupational moderate to vigorous physical activity. We used linear and logistic regressions to test linear trends over time and to identify inequalities by age, sex, and the Scottish Index of Multiple Deprivation quintile. RESULTS: There was an increase in all measures of walking over the period 2012-2021; for example, the percentage reporting any walking increased by 7 percentage points (81.4%-88.4%). Inequalities still exist by age, sex, and the Scottish Index of Multiple Deprivation but have not grown over time. Inequalities by sex and age are most pronounced in the least affluent Scottish Index of Multiple Deprivation quintiles; less affluent older women are least likely to report any walking. CONCLUSIONS: Scotland appears to be walking in the right direction. Surveillance data support a positive trend after decades of policy and promotion efforts. The policies do not appear to be exacerbating existing inequalities, but narrowing them will require more concentrated efforts.
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Classe Social , Caminhada , Humanos , Escócia , Caminhada/estatística & dados numéricos , Feminino , Masculino , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Idoso , Inquéritos Epidemiológicos , Adolescente , Adulto Jovem , Fatores Sexuais , Fatores EtáriosRESUMO
Malnutrition underlies almost half of all child deaths globally. Severe Acute Malnutrition (SAM) carries unacceptable mortality, particularly if accompanied by infection or medical complications, including enteropathy. We evaluated four interventions for malnutrition enteropathy in a multi-centre phase II multi-arm trial in Zambia and Zimbabwe and completed in 2021. The purpose of this trial was to identify therapies which could be taken forward into phase III trials. Children of either sex were eligible for inclusion if aged 6-59 months and hospitalised with SAM (using WHO definitions: WLZ <-3, and/or MUAC <11.5 cm, and/or bilateral pedal oedema), with written, informed consent from the primary caregiver. We randomised 125 children hospitalised with complicated SAM to 14 days treatment with (i) bovine colostrum (n = 25), (ii) N-acetyl glucosamine (n = 24), (iii) subcutaneous teduglutide (n = 26), (iv) budesonide (n = 25) or (v) standard care only (n = 25). The primary endpoint was a composite of faecal biomarkers (myeloperoxidase, neopterin, α1-antitrypsin). Laboratory assessments, but not treatments, were blinded. Per-protocol analysis used ANCOVA, adjusted for baseline biomarker value, sex, oedema, HIV status, diarrhoea, weight-for-length Z-score, and study site, with pre-specified significance of P < 0.10. Of 143 children screened, 125 were randomised. Teduglutide reduced the primary endpoint of biomarkers of mucosal damage (effect size -0.89 (90% CI: -1.69,-0.10) P = 0.07), while colostrum (-0.58 (-1.4, 0.23) P = 0.24), N-acetyl glucosamine (-0.20 (-1.01, 0.60) P = 0.67), and budesonide (-0.50 (-1.33, 0.33) P = 0.32) had no significant effect. All interventions proved safe. This work suggests that treatment of enteropathy may be beneficial in children with complicated malnutrition. The trial was registered at ClinicalTrials.gov with the identifier NCT03716115.