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BACKGROUND: Outcomes in alcohol-associated liver disease (ALD) are influenced by several race and ethnic factors, yet its natural history across the continuum of patients in different stages of the disease is unknown. METHODS: We conducted a retrospective cohort study of U.S. adults from 2011 to 2018, using three nationally representative databases to examine potential disparities in relevant outcomes among racial and ethnic groups. Our analysis included logistic and linear regressions, along with competing risk analysis. RESULTS: Black individuals had the highest daily alcohol consumption (12.6 g/day) while Hispanic participants had the largest prevalence of heavy episodic drinking (33.5%). In a multivariable-adjusted model, Hispanic and Asian participants were independently associated with a higher ALD prevalence compared to Non-Hispanic White interviewees (OR: 1.4, 95% CI: 1.1-1.8 and OR: 1.5 95% CI:1.1-2.0, respectively), while Blacks participants had a lower ALD prevalence (OR: .7 95% CI: .6-.9), and a lower risk of mortality during hospitalization due to ALD (OR: .83 95% CI: .73-.94). Finally, a multivariate competing-risk analysis showed that Hispanic ethnicity had a decreased probability of liver transplantation if waitlisted for ALD (SHR: .7, 95% CI: .6-.8) along with female Asian population (HR: .40, 95% CI: .26-.62). CONCLUSIONS: After accounting for key social and biological health determinants, the Hispanic population showed an increased risk of ALD prevalence, even with lower alcohol consumption. Additionally, Hispanic and Asian female patients had reduced access to liver transplantation compared to other enlisted patients.
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BACKGROUND: The nucleus incertus (NI) was originally described by Streeter in 1903, as a midline region in the floor of the fourth ventricle of the human brain with an 'unknown' function. More than a century later, the neuroanatomy of the NI has been described in lower vertebrates, but not in humans. Therefore, we examined the neurochemical anatomy of the human NI using markers, including the neuropeptide, relaxin-3 (RLN3), and began to explore the distribution of the NI-related RLN3 innervation of the hippocampus. METHODS: Histochemical staining of serial, coronal sections of control human postmortem pons was conducted to reveal the presence of the NI by detection of immunoreactivity (IR) for the neuronal markers, microtubule-associated protein-2 (MAP2), glutamic acid dehydrogenase (GAD)-65/67 and corticotrophin-releasing hormone receptor 1 (CRHR1), and RLN3, which is highly expressed in NI neurons in diverse species. RLN3 and vesicular GABA transporter 1 (vGAT1) mRNA were detected by fluorescent in situ hybridization. Pons sections containing the NI from an AD case were immunostained for phosphorylated-tau, to explore potential relevance to neurodegenerative diseases. Lastly, sections of the human hippocampus were stained to detect RLN3-IR and somatostatin (SST)-IR. RESULTS: In the dorsal, anterior-medial region of the human pons, neurons containing RLN3- and MAP2-IR, and RLN3/vGAT1 mRNA-positive neurons were observed in an anatomical pattern consistent with that of the NI in other species. GAD65/67- and CRHR1-immunopositive neurons were also detected within this area. Furthermore, RLN3- and AT8-IR were co-localized within NI neurons of an AD subject. Lastly, RLN3-IR was detected in neurons within the CA1, CA2, CA3 and DG areas of the hippocampus, in the absence of RLN3 mRNA. In the DG, RLN3- and SST-IR were co-localized in a small population of neurons. CONCLUSIONS: Aspects of the anatomy of the human NI are shared across species, including a population of stress-responsive, RLN3-expressing neurons and a RLN3 innervation of the hippocampus. Accumulation of phosphorylated-tau in the NI suggests its possible involvement in AD pathology. Further characterization of the neurochemistry of the human NI will increase our understanding of its functional role in health and disease.
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Ponte , Humanos , Ponte/metabolismo , Masculino , Hipocampo/química , Hipocampo/metabolismo , Feminino , Relaxina/metabolismo , Relaxina/genética , Idoso , Neurônios/química , Memória/fisiologia , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Glutamato Descarboxilase/metabolismo , Glutamato Descarboxilase/genética , Receptores de Hormônio Liberador da CorticotropinaRESUMO
INTRODUCTION: This study investigates primary lateral sclerosis (PLS) as a rare manifestation of the presenilin 1 (PSEN1) NM_000021 c.851C > T p.Pro284Leu variant in three siblings of a Colombian family, outlining its clinical and neuropathological features and their relationship to Alzheimer's disease (AD). METHODS: Data were gathered using clinical evaluations, next-generation genetic sequencing, magnetic resonance imaging, biomarker analysis, and neuropathological examination. RESULTS: Carriers of the PSEN1 Pro284Leu variant exhibited classic PLS symptoms, including unilateral onset and bulbar syndromes, along with cognitive decline. Neuropathology showed corticospinal tract degeneration without amyloid beta deposition in spinal white matter. DISCUSSION: Our findings suggest an overlap between PLS and AD pathology in PSEN1 variant carriers. Results support considering PLS when diagnosing AD-related motor syndromes and including PSEN1 evaluation when performing genetic testing for PLS. The study highlights the need for further research to clarify the PLS-AD relationship, informing future treatments and clinical trials. HIGHLIGHTS: Pathogenic variants in presenilin 1 (PSEN1) can manifest as hereditary primary lateral sclerosis PSEN1 Pro284Leu carriers present motor, cognitive, and behavioral alterations Cases had corticospinal tract microgliosis and severe Aß pathology in motor cortex There was no evidence of amyloid deposition in the spinal cord white matter All the neuropathology images are available for online visualization Myelin pallor in the spinal cord is confined to the lateral corticospinal tracts.
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In countries where soil-transmitted helminth (STH) infections are endemic, deworming programs are recommended to reduce morbidity; however, increasing levels of resistance to benzimidazoles are of concern. In an observational study in Peru, we studied the clinical efficacy of 400 mg of albendazole 20 days after treatment among children aged 2-11 years. Of 426 participants who provided samples, 52.3% were infected with a STH, 144 (33.8%) were positive for Ascaris (41.8% light, 50.8% moderate, and 7.4% heavy infections), 147 (34.5%) were positive for Trichuris (75.2% light, 22.5% moderate, and 2.3% heavy infections), and 1.1% were positive for hookworm species (100% light infections). Additional stool samples were examined at 20, 90, and 130 days after the initial treatment. At 20 days post-administration of albendazole, the cure rate (CR) of Ascaris infection was 80.1% (95% CI: 73.5-86.7), and the egg reduction rate (ERR) was 70.8% (95% CI: 57.8-88.7); the CR for Trichuris infection was 27.1% (95% CI: 20.0-34.3), and the ERR was 29.8% (95% CI: -1.40 to 57.5). Among participants with persistent or recurrent infections with Trichuris, the combined therapy of albendazole (400 mg) and ivermectin at 600 µg/dose increased overall CR for Trichuris infection to 75.2% (95% CI: 67.3-83.2%) with an ERR of 84.2% (95% CI: 61.3-93.8%). Albendazole administration alone for the control of STH was associated with high rates of treatment failure, especially for Trichuris. Combined single doses of albendazole and ivermectin was observed to have improved efficacy.
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Albendazol , Anti-Helmínticos , Helmintíase , Ivermectina , Solo , Humanos , Albendazol/uso terapêutico , Albendazol/administração & dosagem , Peru/epidemiologia , Pré-Escolar , Criança , Ivermectina/uso terapêutico , Ivermectina/administração & dosagem , Masculino , Feminino , Solo/parasitologia , Helmintíase/tratamento farmacológico , Helmintíase/epidemiologia , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/administração & dosagem , Fezes/parasitologia , Quimioterapia Combinada , Animais , Resultado do Tratamento , Tricuríase/tratamento farmacológico , Tricuríase/epidemiologia , Ascaríase/tratamento farmacológico , Ascaríase/epidemiologia , Trichuris/efeitos dos fármacosRESUMO
CONTEXT: There is strong evidence that racial and ethnic disparities exist in multiple arenas of health and wellness. The causes of racial and ethnic differences in health care are multidimensional; one factor that may affect injury/illness communication, interactions, and outcomes is patient-provider racial and ethnic concordance. At present, it is unclear what role patient-provider racial and ethnic concordance and discordance plays in facilitating concussion care for collegiate athletes. OBJECTIVE: To investigate the presence of athlete-athletic trainer (AT) racial and ethnic concordance and discordance among diagnosed concussion cases and examine if racial and ethnic concordance and discordance influences time (in days) until diagnosis, symptom resolution, or return-to-sport clinical milestones in collegiate athletes. DESIGN: Retrospective cohort study. SETTING: Collegiate athletics. PATIENTS OR OTHER PARTICIPANTS: A total of 694 concussion cases (38.6% [n = 268] sustained by women, 61.4% [n = 426] sustained by men) that occurred within the 2015-2016 through 2019-2020 sport seasons at 9 institutions. MAIN OUTCOME MEASURE(S): The number of days from the date of injury to diagnosis, symptom resolution, and return to sport and from the date of diagnosis to symptom resolution and return to sport. RESULTS: Overall, 68.4% (n = 475) of concussion cases had patient-provider racial and ethnic concordance, and 31.6% (n = 219) were discordant. All concordant pairs included a White athlete and White AT. Time to diagnosis differed between the concordant and discordant groups (median [interquartile range] = 1 [0-2] versus 0 [0-1], respectively) only in the model adjusted for sex, sport type, and availability of an AT (odds ratio [95% CI] = 1.46 [1.07-1.85]). There were no other group differences. CONCLUSIONS: One-third of concussion cases had athlete-AT racial and ethnic discordance. Although this group was diagnosed with a concussion 1 day sooner than the concordant group, no differences were observed for any concussion recovery milestones. These findings suggest that patient-provider racial and ethnic concordance may play a minor role in concussion recognition or reporting but not necessarily in the management and recovery thereafter.
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Traumatismos em Atletas , Concussão Encefálica , Volta ao Esporte , Humanos , Concussão Encefálica/terapia , Concussão Encefálica/diagnóstico , Masculino , Feminino , Estudos Retrospectivos , Traumatismos em Atletas/terapia , Traumatismos em Atletas/etnologia , Universidades , Atletas , Etnicidade , Adulto Jovem , Disparidades em Assistência à Saúde/etnologia , Grupos RaciaisRESUMO
Support groups can create environments that are conducive to healing and well-being, particularly for persons with stigmatizing chronic diseases. In 1998, the support group concept was adapted in Haiti for persons with disabling lymphedema caused by lymphatic filariasis (LF). The project was developed with the expectation that the support group model conceived in the developed world be interpreted and modified by persons affected with lymphedema in the Haitian setting. Initiated with modest financial support within a research initiative to eliminate LF, a total of 50 "Hope Clubs" were formed from 1998 to 2023 across seven communes (districts) located in 3 of Haiti's 10 regional Departments. Documented benefits of the support groups included improved limb self-care, decreased incidence of inflammatory episodes (adenolymphangitis), enhanced self-efficacy, economic benefit through microenterprise, and improved quality of life. Despite challenges of funding shortfalls, natural disasters, and political insecurity, persistence of LF support groups in Haiti highlights the crucial role of group ownership by affected persons and the freedom to reinvent the support group concept in light of local social, cultural, and economic conditions.
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Filariose Linfática , Grupos de Autoajuda , Haiti/epidemiologia , Humanos , Filariose Linfática/epidemiologia , Qualidade de VidaRESUMO
OBJECTIVE: Determine self-reported parental feeding behavior changes and perspectives on parental feeding intervention at 12-month follow-up. METHODS: Telephone focus groups using a 2 × 2 design (English/Spanish × in-class or online) with Expanded Food and Nutrition Education Program participants (n = 37) with children 2-8 years and high exposure to the Food, Feeding, and Your Family intervention (7 lessons). Researchers (n = 3) independently identified themes. RESULTS: Parental behavior changes that (1) positively influenced children's diets, (2) involved children in food-related activities, (3) eased stressful situations around food, (4) led to healthier food choices, and (5) saved money when food shopping. Commonly implemented practices included establishing structured mealtime routines, introducing new foods multiple times, and encouraging children's eating competence. Online participants noted materials were easily accessible via text messages. CONCLUSIONS AND IMPLICATIONS: Incorporating parental feeding content (in-class or online) into nutrition education interventions, such as the Expanded Food and Nutrition Education Program, supports developing positive parental feeding behaviors in families with low income.
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Comportamento Alimentar , Grupos Focais , Pais , Humanos , Pais/psicologia , Comportamento Alimentar/psicologia , Feminino , Masculino , Pré-Escolar , Criança , Adulto , Educação em Saúde/métodos , SeguimentosRESUMO
BACKGROUND & AIMS: The long-term impact of alcohol-related public health policies (PHPs) on disease burden is unclear. We aimed to assess the association between alcohol-related PHPs and alcohol-related health consequences. METHODS: We conducted an ecological multi-national study including 169 countries. We collected data on alcohol-related PHPs from the WHO Global Information System of Alcohol and Health 2010. Data on alcohol-related health consequences between 2010-2019 were obtained from the Global Burden of Disease database. We classified PHPs into five items, including criteria for low, moderate, and strong PHP establishment. We estimated an alcohol preparedness index (API) using multiple correspondence analysis (0 lowest and 100 highest establishment). We estimated an incidence rate ratio (IRR) for outcomes according to API using adjusted multilevel generalized linear models with a Poisson family distribution. RESULTS: The median API in the 169 countries was 54 [IQR 34.9-76.8]. The API was inversely associated with alcohol use disorder (AUD) prevalence (IRR 0.13; 95% CI 0.03-0.60; p = 0.010), alcohol-associated liver disease (ALD) mortality (IRR 0.14; 95% CI 0.03-0.79; p = 0.025), mortality due to neoplasms (IRR 0.09; 95% CI 0.02-0.40; p = 0.002), alcohol-attributable hepatocellular carcinoma (HCC) (IRR 0.13; 95% CI 0.02-0.65; p = 0.014), and cardiovascular diseases (IRR 0.09; 95% CI 0.02-0.41; p = 0.002). The highest associations were observed in the Americas, Africa, and Europe. These associations became stronger over time, and AUD prevalence was significantly lower after 2 years, while ALD mortality and alcohol-attributable HCC incidence decreased after 4 and 8 years from baseline API assessment, respectively (p <0.05). CONCLUSIONS: The API is a valuable instrument to quantify the robustness of alcohol-related PHP establishment. Lower AUD prevalence and lower mortality related to ALD, neoplasms, alcohol-attributable HCC, and cardiovascular diseases were observed in countries with a higher API. Our results encourage the development and strengthening of alcohol-related policies worldwide. IMPACT AND IMPLICATIONS: We first developed an alcohol preparedness index, an instrument to assess the existence of alcohol-related public policies for each country. We then evaluated the long-term association of the country's alcohol preparedness index in 2010 with the burden of chronic liver disease, hepatocellular carcinoma, other neoplasms, and cardiovascular disease. The strengthening of alcohol-related public health policies could impact long-term mortality rates from cardiovascular disease, neoplasms, and liver disease. These conditions are the main contributors to the global burden of disease related to alcohol use. Over time, this association has not only persisted but also grown stronger. Our results expand the preliminary evidence regarding the importance of public health policies in controlling alcohol-related health consequences.
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Alcoolismo , Carcinoma Hepatocelular , Doenças Cardiovasculares , Hepatopatias Alcoólicas , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/complicações , Hepatopatias Alcoólicas/patologia , Alcoolismo/complicações , Política Pública , Política de SaúdeRESUMO
Long non-coding RNAs (lncRNAs) comprise the most representative transcriptional units of the mammalian genome. They are associated with organ development linked with the emergence of cardiovascular diseases. We used bioinformatic approaches, machine learning algorithms, systems biology analyses, and statistical techniques to define co-expression modules linked to heart development and cardiovascular diseases. We also uncovered differentially expressed transcripts in subpopulations of cardiomyocytes. Finally, from this work, we were able to identify eight cardiac cell-types; several new coding, lncRNA, and pcRNA markers; two cardiomyocyte subpopulations at four different time points (ventricle E9.5, left ventricle E11.5, right ventricle E14.5 and left atrium P0) that harbored co-expressed gene modules enriched in mitochondrial, heart development and cardiovascular diseases. Our results evidence the role of particular lncRNAs in heart development and highlight the usage of co-expression modular approaches in the cell-type functional definition.
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Doenças Cardiovasculares , RNA Longo não Codificante , Animais , Camundongos , RNA Longo não Codificante/genética , Perfilação da Expressão Gênica/métodos , Organogênese , Miócitos Cardíacos , Mamíferos/genéticaRESUMO
BACKGROUND: Atrial fibrillation (AF) is a major risk factor for stroke. To enable improvements to AF diagnosis and follow-up care, understanding current patient pathways and barriers to optimal care are essential. We investigated the patient care pathways and their drivers, and the impact of the COVID-19 pandemic on patient pathways in a middle-income country setting, Brazil. METHODS: This mixed-methods study in São Paulo, included adults (≥18y) with AF from 13 primary/secondary healthcare facilities. Surveys using baseline, follow-up (administered ≥two months after baseline) and COVID-19 questionnaires (quantitative), and three focus group discussions (FGDs) were conducted. Minimum sample size for the quantitative component was 236 and we aimed to reach saturation with at least three FGDs for the qualitative component. Descriptive statistics were used for quantitative data and a content analysis was used for qualitative data to identify themes related to AF diagnosis and follow-up care. RESULTS: 267 participants completed the baseline questionnaire: 25% were diagnosed in primary care, 65% in an emergency or inpatient department. At follow-up (n = 259), 31% visited more than one facility for AF care, and 7% had no follow-up. Intervals between international normalised ratio (INR) tests were increased during the pandemic, and the number of healthcare visits and availability of medication were reduced. Seventeen patients participated in three FGDs and revealed that AF diagnosis often occurred following a medical emergency and patients often delay care-seeking due to misconceptions about AF symptoms. Long waiting times, doctor/patient interactions and health system factors, such as doctor availability and the referral system, influence where participants visited for follow-up care. CONCLUSIONS: Lack of public awareness and underdeveloped primary healthcare lead to delayed diagnosis, which impacts clinical outcomes and excess patient and healthcare system costs. Health system, care-provider, and pandemic factors disrupt timely and effective continuity of care.