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1.
medRxiv ; 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38946970

RESUMEN

INTRODUCTION: Blood tests have the potential to improve the accuracy of Alzheimer disease (AD) clinical diagnosis, which will enable greater access to AD-specific treatments. This study compared leading commercial blood tests for amyloid pathology and other AD-related outcomes. METHODS: Plasma samples from the Alzheimers Disease Neuroimaging Initiative were assayed with AD blood tests from C2N Diagnostics, Fujirebio Diagnostics, ALZPath, Janssen, Roche Diagnostics, and Quanterix. Outcomes measures were amyloid positron emission tomography (PET), tau PET, cortical thickness, and dementia severity. Logistic regression models assessed the classification accuracies of individual or combined plasma biomarkers for binarized outcomes, and Spearman correlations evaluated continuous relationships between individual plasma biomarkers and continuous outcomes. RESULTS: Measures of plasma p-tau217, either individually or in combination with other plasma biomarkers, had the strongest relationships with all AD outcomes. DISCUSSION: This study identified the plasma biomarker analytes and assays that most accurately classified amyloid pathology and other AD-related outcomes.

2.
J Huntingtons Dis ; 13(2): 119-131, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38968054

RESUMEN

The field of Huntington's disease research covers many different scientific disciplines, from molecular biology all the way through to clinical practice, and as our understanding of the disease has progressed over the decades, a great deal of different terminology has accrued. The field is also renowned for its collaborative spirit and use of standardized reagents, assays, datasets, models, and clinical measures, so the use of standardized terms is especially important. We have set out to determine, through a consensus exercise involving basic and clinical scientists working in the field, the most appropriate language to use across disciplines. Nominally, this article will serve as the style guide for the Journal of Huntington's Disease (JHD), the only journal devoted exclusively to HD, and we lay out the preferred and standardized terminology and nomenclature for use in JHD publications. However, we hope that this article will also serve as a useful resource to the HD research community at large and that these recommended naming conventions will be adopted widely.


Asunto(s)
Enfermedad de Huntington , Terminología como Asunto , Enfermedad de Huntington/clasificación , Enfermedad de Huntington/diagnóstico , Humanos , Investigación Biomédica/normas
3.
Nat Commun ; 15(1): 5539, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956096

RESUMEN

Blood-based biomarkers of Alzheimer disease (AD) may facilitate testing of historically under-represented groups. The Study of Race to Understand Alzheimer Biomarkers (SORTOUT-AB) is a multi-center longitudinal study to compare AD biomarkers in participants who identify their race as either Black or white. Plasma samples from 324 Black and 1,547 white participants underwent analysis with C2N Diagnostics' PrecivityAD test for Aß42 and Aß40. Compared to white individuals, Black individuals had higher average plasma Aß42/40 levels at baseline, consistent with a lower average level of amyloid pathology. Interestingly, this difference resulted from lower average levels of plasma Aß40 in Black participants. Despite the differences, Black and white individuals had similar longitudinal rates of change in Aß42/40, consistent with a similar rate of amyloid accumulation. Our results agree with multiple recent studies demonstrating a lower prevalence of amyloid pathology in Black individuals, and additionally suggest that amyloid accumulates consistently across both groups.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Biomarcadores , Fragmentos de Péptidos , Población Blanca , Humanos , Péptidos beta-Amiloides/sangre , Masculino , Femenino , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/etnología , Estudios Longitudinales , Anciano , Fragmentos de Péptidos/sangre , Biomarcadores/sangre , Negro o Afroamericano , Persona de Mediana Edad , Anciano de 80 o más Años , Población Negra
4.
HGG Adv ; 5(3): 100318, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38872308

RESUMEN

The high heritability of amyotrophic lateral sclerosis (ALS) contrasts with its low molecular diagnosis rate post-genetic testing, pointing to potential undiscovered genetic factors. To aid the exploration of these factors, we introduced EpiOut, an algorithm to identify chromatin accessibility outliers that are regions exhibiting divergent accessibility from the population baseline in a single or few samples. Annotation of accessible regions with histone chromatin immunoprecipitation sequencing and Hi-C indicates that outliers are concentrated in functional loci, especially among promoters interacting with active enhancers. Across different omics levels, outliers are robustly replicated, and chromatin accessibility outliers are reliable predictors of gene expression outliers and aberrant protein levels. When promoter accessibility does not align with gene expression, our results indicate that molecular aberrations are more likely to be linked to post-transcriptional regulation rather than transcriptional regulation. Our findings demonstrate that the outlier detection paradigm can uncover dysregulated regions in rare diseases. EpiOut is available at github.com/uci-cbcl/EpiOut.

5.
Mol Metab ; 86: 101976, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38925248

RESUMEN

OBJECTIVES: A high proportion of women with advanced epithelial ovarian cancer (EOC) experience weakness and cachexia. This relationship is associated with increased morbidity and mortality. EOC is the most lethal gynecological cancer, yet no preclinical cachexia model has demonstrated the combined hallmark features of metastasis, ascites development, muscle loss and weakness in adult immunocompetent mice. METHODS: Here, we evaluated a new model of ovarian cancer-induced cachexia with the advantages of inducing cancer in adult immunocompetent C57BL/6J mice through orthotopic injections of EOC cells in the ovarian bursa. We characterized the development of metastasis, ascites, muscle atrophy, muscle weakness, markers of inflammation, and mitochondrial stress in the tibialis anterior (TA) and diaphragm ∼45, ∼75 and ∼90 days after EOC injection. RESULTS: Primary ovarian tumour sizes were progressively larger at each time point while severe metastasis, ascites development, and reductions in body, fat and muscle weights occurred by 90 Days. There were no changes in certain inflammatory (TNFα), atrogene (MURF1 and Atrogin) or GDF15 markers within both muscles whereas IL-6 was increased at 45 and 90 Day groups in the diaphragm. TA weakness in 45 Day preceded atrophy and metastasis that were observed later (75 and 90 Day, respectively). The diaphragm demonstrated both weakness and atrophy in 45 Day. In both muscles, this pre-severe-metastatic muscle weakness corresponded with considerable reprogramming of gene pathways related to mitochondrial bioenergetics as well as reduced functional measures of mitochondrial pyruvate oxidation and creatine-dependent ADP/ATP cycling as well as increased reactive oxygen species emission (hydrogen peroxide). Remarkably, muscle force per unit mass at 90 days was partially restored in the TA despite the presence of atrophy and severe metastasis. In contrast, the diaphragm demonstrated progressive weakness. At this advanced stage, mitochondrial pyruvate oxidation in both muscles exceeded control mice suggesting an apparent metabolic super-compensation corresponding with restored indices of creatine-dependent adenylate cycling. CONCLUSIONS: This mouse model demonstrates the concurrent development of cachexia and metastasis that occurs in women with EOC. The model provides physiologically relevant advantages of inducing tumour development within the ovarian bursa in immunocompetent adult mice. Moreover, the model reveals that muscle weakness in both TA and diaphragm precedes severe metastasis while weakness also precedes atrophy in the TA. An underlying mitochondrial bioenergetic stress corresponded with this early weakness. Collectively, these discoveries can direct new research towards the development of therapies that target pre-atrophy and pre-severe-metastatic weakness during EOC in addition to therapies targeting cachexia.

6.
Violence Against Women ; : 10778012241259712, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38870450

RESUMEN

Groups are a common clinical intervention for women survivors of intimate partner violence (IPV). This secondary mixed-methods analysis from a study of 567 Canadian women from the prairie provinces compared the mental health and well-being of 131 women who had attended a IPV group to 436 women who had not attended any group. Qualitatively, perspectives from 131 women (113 comments; 18 interviews) who attended some form of group treatment were analyzed. Of the 199 coded comments about the IPV groups, most were positive (157 or 78.9%), while the remaining 21.1% (42) reflected concerns or suggested changes. Clinical implications are provided.

7.
Aquat Toxicol ; 273: 106982, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38861791

RESUMEN

Pollution from regularly used substances such as pharmaceuticals, cleaning agents, and even food and beverages is an increasing problem in the environment. Caffeine, a commonly ingested stimulant, is one such contaminant that has been detected in aquatic environments worldwide. Yet, little is known about how ecologically relevant concentrations of caffeine influence the morphology, behaviour, and physiology of exposed organisms. To address this knowledge gap, we exposed fathead minnow (Pimephales promelas) to three caffeine treatments: a freshwater control (nominal: 0 ng/L), a low (nominal: 1,000 ng/L) and high environmentally relevant dose (nominal: 10,000 ng/L), for 35 days. We tested the learning abilities, anxiety, metabolic rates, and morphological features of exposed vs. control fish. Caffeine exposure did not affect the ability of fish to learn but did influence anxiety levels. Over the course of repeated anxiety testing, unexposed control fish visited a black square more often while fish exposed to low levels of caffeine did not, potentially indicating that these fish remained in a more anxious state. While caffeine did not impact metabolism, fish growth, or body size, it was associated with lower liver investment-although this response was only observed in our low caffeine treatment. Overall, our results suggest that even relatively low concentrations of caffeine may impact the liver size and anxiety of exposed fish, but further research is needed to assess how extended exposure to caffeine impacts fitness. Given the increase in anthropogenic contaminants in aquatic environments, it is important that we continue to investigate their effects on the organisms exposed to them.

8.
Int J Womens Health ; 16: 1079-1091, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38884052

RESUMEN

Purpose: To investigate the associations between anxiety symptoms in midlife women and sleep features later in life, the aim is to test the hypothesis that poor sleep, as measured by each of six individual dimensions (4 objective actigraphy measures, 2 self-reports) of sleep health, is associated with higher levels of anxiety symptoms in midlife women. Participants and Methods: The participants in this longitudinal analysis included women from the SWAN Sleep I Study, a subcohort of the community-dwelling midlife women participating in the core Study of Women's Health Across the Nation (SWAN), which was initiated in 1996. Of the 370 participants enrolled in the Sleep Study, 270 were included in the analytic sample, and 100 who did not meet the inclusion criteria were excluded. Baseline measures of six dimensions of multidimensional sleep health (actigraphy measures: efficiency, duration, mid-sleep timing, regularity; self-report measures: alertness, satisfaction) were obtained between 2003 and 2005, corresponding to SWAN core annual/biennial assessments 5-8. Associations of each dimension with self-reported anxiety symptoms (Generalized Anxiety Disorder - 7-item scale; GAD-7), collected during visits 12 (2009-2011), 13 (2011-2013), and 15 (2015-2017), were examined using mixed models. The GAD-7 outcome was measured both continuously and as a categorical variable due to its skewed distribution. Results: No statistically significant associations were found between any of the six baseline sleep health dimensions and the GAD-7 score after adjustment for covariates. Conclusion: The reasons for the lack of support for our hypothesis, despite previous evidence supporting an association between sleep and anxiety, are unclear. There is considerable overlap between anxiety and sleep symptoms, which may complicate the interpretation of our the findings. Thus, the failure to identify associations is likely multifactorial, and more studies with shorter follow-up intervals are warranted to better understand these relationships.

9.
PLoS One ; 19(6): e0304761, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38843265

RESUMEN

Type 2 diabetes predisposes patients to heart disease, which is the primary cause of death across the globe. Type 2 diabetes often accompanies obesity and is defined by insulin resistance and abnormal glucose handling. Insulin resistance impairs glucose uptake and results in hyperglycemia, which damages tissues such as kidneys, liver, and heart. 2-oxoglutarate (2-OG)- and iron-dependent oxygenases (2-OGDOs), a family of enzymes regulating various aspects of cellular physiology, have been studied for their role in obesity and diet-induced insulin resistance. However, nothing is known of the 2-OGDO family member 2-oxoglutarate and iron-dependent prolyl hydroxylase domain containing protein 1 (OGFOD1) in this setting. OGFOD1 deletion leads to protection in cardiac ischemia-reperfusion injury and cardiac hypertrophy, which are two cardiac events that can lead to heart failure. Considering the remarkable correlation between heart disease and diabetes, the cardioprotection observed in OGFOD1-knockout mice led us to challenge these knockouts with high-fat diet. Wildtype mice fed a high-fat diet developed diet-induced obesity, insulin resistance, and glucose intolerance, but OGFOD1 knockout mice fed this same diet were resistant to diet-induced obesity and insulin resistance. These results support OGFOD1 down-regulation as a strategy for preventing obesity and insulin handling defects.


Asunto(s)
Dieta Alta en Grasa , Resistencia a la Insulina , Ratones Noqueados , Obesidad , Animales , Obesidad/metabolismo , Obesidad/genética , Ratones , Dieta Alta en Grasa/efectos adversos , Masculino , Prolil Hidroxilasas/metabolismo , Prolil Hidroxilasas/genética , Intolerancia a la Glucosa/metabolismo , Intolerancia a la Glucosa/genética , Ratones Endogámicos C57BL , Eliminación de Gen , Cardiomegalia/metabolismo , Cardiomegalia/prevención & control , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/genética
11.
Environ Toxicol Chem ; 43(7): 1569-1582, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38695684

RESUMEN

Wastewater treatment plant (WWTP) effluent often releases pharmaceuticals like venlafaxine (a serotonin-norephinephrine reuptake inhibitor antidepressant) to freshwater ecosystems at levels causing adverse metabolic effects on fish. Changes to fish metabolism can be regulated by epigenetic mechanisms like microRNA (small RNA molecules that regulate mRNA translation), including regulating mitochondrial mRNAs. Nuclear-encoded microRNAs regulate mitochondrial gene expression in mammals, and have predicted effects in fish. We aimed to identify whether venlafaxine exposure changed mitochondrial respiration and resulted in differentially abundant mitochondrial microRNA (mitomiRs) in zebrafish brains. In vitro exposure of brain homogenate to below environmentally relevant concentrations of venlafaxine (<1 µg/L) caused a decrease in mitochondrial respiration, although this was not driven by changes to mitochondrial Complex I or II function. To identify whether these effects occur in vivo, zebrafish were exposed to 1 µg/L venlafaxine for 0, 1, 6, 12, 24, and 96 h. In vivo, venlafaxine exposure had no significant effects on brain mitochondrial respiration; however, select mitomiRs (dre-miR-301a-5p, dre-miR-301b-3p, and dre-miR-301c-3p) were also measured, because they were bioinformatically predicted to regulate mitochondrial cytochrome c oxidase subunit I (COI) abundance. These mitomiRs were differentially regulated based on venlafaxine exposure (with miR-301c-3p abundance differing during the day and miR-301b-3p being lower in exposed fish at night), and with respect to sex and time sampled. Overall, the results demonstrated that in vitro venlafaxine exposure to zebrafish brain caused a decrease in mitochondrial respiration, but these effects were not seen after acute in vivo exposure. Results may have differed because in vivo exposure allows for fish to mitigate effects through mechanisms that could include mitomiR regulation, and because fish were only acutely exposed. Environ Toxicol Chem 2024;43:1569-1582. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


Asunto(s)
Encéfalo , MicroARNs , Mitocondrias , Clorhidrato de Venlafaxina , Contaminantes Químicos del Agua , Pez Cebra , Animales , Clorhidrato de Venlafaxina/toxicidad , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Contaminantes Químicos del Agua/toxicidad , Respiración de la Célula/efectos de los fármacos
12.
JAMA Ophthalmol ; 142(6): 540-546, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38722650

RESUMEN

Importance: Known social risk factors associated with poor visual and systemic health in the US include segregation, income inequality, and persistent poverty. Objective: To investigate the association of vision difficulty, including blindness, in neighborhoods with measures of inequity (Theil H index, Gini index, and persistent poverty). Design, Setting, and Participants: This cross-sectional study used data from the 2012-2016 American Community Survey and 2010 US census tracts as well as Theil H index, Gini index, and persistent poverty measures from PolicyMap. Data analysis was completed in July 2023. Main Outcomes and Measures: The main outcome was the number of census tract residents reporting vision difficulty and blindness (VDB) and the association with the Theil H index, Gini index, or persistent poverty, assessed using logistic regression. Results: In total, 73 198 census tracts were analyzed. For every 0.1-unit increase in Theil H index and Gini index, there was an increased odds of VDB after controlling for census tract-level median age, the percentage of the population that identified as female sex, the percentage of the population that identified as a member of a racial or ethnic minority group, state, and population size (Theil H index: odds ratio [OR], 1.14 [95% CI, 1.14-1.14; P < .001]; Gini index: OR, 1.15 [95% CI, 1.15-1.15; P < .001]). Persistent poverty was associated with an increased odds of VDB after controlling for census tract-level median age, the percentage of the population that identified as female sex, the percentage of the population that identified as a member of a racial or ethnic minority group, state, and population size compared with nonpersistent poverty (OR, 1.36; 95% CI, 1.35-1.36; P < .001). Conclusions and Relevance: In this cross-sectional study, residential measures of inequity through segregation, income inequality, or persistent poverty were associated with a greater number of residents living with VDB. It is essential to understand and address how neighborhood characteristics can impact rates of VDB.


Asunto(s)
Ceguera , Humanos , Estudios Transversales , Masculino , Femenino , Ceguera/epidemiología , Estados Unidos/epidemiología , Persona de Mediana Edad , Anciano , Adulto , Factores Socioeconómicos , Factores de Riesgo , Pobreza , Características del Vecindario , Inequidades en Salud
13.
J Urol ; 212(1): 124-135, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38703067

RESUMEN

PURPOSE: We aimed to estimate the prevalence of a wide range of lower urinary tract symptoms (LUTS) in US women, and explore associations with bother and discussion with health care providers, friends, and family. MATERIALS AND METHODS: We analyzed baseline data collected from May 2022 to December 2023 in the RISE FOR HEALTH study-a large, regionally representative cohort study of adult female community members. LUTS and related bother were measured by the 10-item Symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index, and discussion was assessed by a study-specific item. RESULTS: Of the 3000 eligible participants, 73% (95% CI 71%-74%) reported any storage symptoms, 52% (95% CI 50%-53%) any voiding or emptying symptoms, and 11% (95% CI 10%-13%) any pain with bladder filling, for an overall LUTS prevalence of 79% (95% CI 78%-81%). This prevalence estimate included 43% (95% CI 41%-45%) of participants with mild to moderate symptoms and 37% (95% CI 35%-38%) with moderate to severe symptoms. Over one-third of participants reported LUTS-related bother (38%, 95% CI 36%-39%) and discussion (38%, 95% CI 36%-40%), whereas only 7.1% (95% CI 6.2%-8.1%) reported treatment. Urgency and incontinence (including urgency and stress incontinence) were associated with the greatest likelihood of bother and/or discussion (adjusted prevalence ratios = 1.3-2.3), even at mild to moderate levels. They were also the most commonly treated LUTS. CONCLUSIONS: LUTS, particularly storage LUTS such as urgency and incontinence, were common and bothersome in the RISE study population, yet often untreated. Given this large burden, both prevention and treatment-related interventions are warranted to reduce the high prevalence and bother of LUTS.


Asunto(s)
Síntomas del Sistema Urinario Inferior , Humanos , Síntomas del Sistema Urinario Inferior/epidemiología , Femenino , Prevalencia , Estados Unidos/epidemiología , Persona de Mediana Edad , Anciano , Adulto , Estudios de Cohortes
14.
Microbiome ; 12(1): 89, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745230

RESUMEN

BACKGROUND: Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. RESULT: Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. CONCLUSION: These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. Video Abstract.


Asunto(s)
Fibras de la Dieta , Suplementos Dietéticos , Microbioma Gastrointestinal , Inulina , Ratones Endogámicos C57BL , Psyllium , Neoplasias de la Vejiga Urinaria , Animales , Ratones , Microbioma Gastrointestinal/efectos de los fármacos , Inulina/administración & dosificación , Neoplasias de la Vejiga Urinaria/radioterapia , Neoplasias de la Vejiga Urinaria/patología , Humanos , Femenino , Traumatismos por Radiación/prevención & control , Intestinos/microbiología , Intestinos/efectos de la radiación , Linfocitos T CD8-positivos
15.
Wilderness Environ Med ; : 10806032241248626, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38706212

RESUMEN

The Women in Wilderness Medicine Research Committee of the Wilderness Medical Society conducted a narrative review to address considerations for pregnant individuals in wilderness environments. There is limited evidence behind many opinion-based recommendations on the safety of various environmental exposures in pregnancy. The authors reviewed the literature for the best available evidence, including observational studies, case series, limited controlled trials, and extrapolation from physiological data, as well as evaluating expert consensus statements. The benefits of exposure to natural environments include better pregnancy outcomes and improved maternal mental and physical health. Risks are similar to nonpregnant individuals with the added risks associated with maternal-fetal physiology in wilderness environments and difficulties of evacuation. This narrative review discusses pregnancy-specific concerns in extreme environments, including high altitude, hypothermia, hyperthermia, lightning strikes, envenomations, and common outdoor exposures.

16.
J Interprof Care ; 38(4): 632-641, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38743046

RESUMEN

The COVID-19 pandemic has affected over 700 million people globally, straining healthcare systems and highlighting the need for interprofessional collaboration. The aim of this study was to describe interprofessional collaborative practice (IPCP) experiences from the perspectives of occupational therapists (OTs) and physical therapists (PTs) who were employed in a medical center both before and during the COVID-19 pandemic. This qualitative study, conducted from July 2020-November 2021, delved into the lived experiences of occupational and physical therapists in an inpatient setting during the pandemic through analysis of semi-structured interviews and journal entries. The pandemic prompted fear, uncertainty, and ethical dilemmas among therapists, affecting patient-centered care. Roles expanded, and teamwork challenges emerged in defining boundaries, while communication dynamics were transformed by virtual technologies. The pandemic affected therapists' values and ethics, and evolving roles brought expanded tasks. The crisis showcased both collaboration potential and the need to address team disparities. This study highlights the significance of values, roles, teams, and communication for occupational and physical therapists during the COVID-19 pandemic providing valuable insights into interprofessional collaboration's effect on healthcare delivery in times of crisis and beyond.


Asunto(s)
COVID-19 , Conducta Cooperativa , Relaciones Interprofesionales , Terapeutas Ocupacionales , Fisioterapeutas , Investigación Cualitativa , SARS-CoV-2 , Humanos , Fisioterapeutas/psicología , Terapeutas Ocupacionales/psicología , Grupo de Atención al Paciente/organización & administración , Pandemias , Masculino , Femenino , Adulto , Actitud del Personal de Salud , Persona de Mediana Edad , Entrevistas como Asunto , Pacientes Internos/psicología , Rol Profesional
17.
Nat Commun ; 15(1): 3606, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38697975

RESUMEN

Amyotrophic Lateral Sclerosis (ALS), like many other neurodegenerative diseases, is highly heritable, but with only a small fraction of cases explained by monogenic disease alleles. To better understand sporadic ALS, we report epigenomic profiles, as measured by ATAC-seq, of motor neuron cultures derived from a diverse group of 380 ALS patients and 80 healthy controls. We find that chromatin accessibility is heavily influenced by sex, the iPSC cell type of origin, ancestry, and the inherent variance arising from sequencing. Once these covariates are corrected for, we are able to identify ALS-specific signals in the data. Additionally, we find that the ATAC-seq data is able to predict ALS disease progression rates with similar accuracy to methods based on biomarkers and clinical status. These results suggest that iPSC-derived motor neurons recapitulate important disease-relevant epigenomic changes.


Asunto(s)
Esclerosis Amiotrófica Lateral , Células Madre Pluripotentes Inducidas , Neuronas Motoras , Humanos , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/patología , Esclerosis Amiotrófica Lateral/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Neuronas Motoras/metabolismo , Neuronas Motoras/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios de Casos y Controles , Cromatina/metabolismo , Cromatina/genética , Anciano , Epigenómica/métodos , Secuenciación de Inmunoprecipitación de Cromatina/métodos , Progresión de la Enfermedad , Epigénesis Genética
18.
Alzheimers Dement ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38770829

RESUMEN

INTRODUCTION: Alzheimer's disease (AD) pathology is defined by ß-amyloid (Aß) plaques and neurofibrillary tau, but Lewy bodies (LBs; 𝛼-synuclein aggregates) are a common co-pathology for which effective biomarkers are needed. METHODS: A validated α-synuclein Seed Amplification Assay (SAA) was used on recent cerebrospinal fluid (CSF) samples from 1638 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, 78 with LB-pathology confirmation at autopsy. We compared SAA outcomes with neuropathology, Aß and tau biomarkers, risk-factors, genetics, and cognitive trajectories. RESULTS: SAA showed 79% sensitivity and 97% specificity for LB pathology, with superior performance in identifying neocortical (100%) compared to limbic (57%) and amygdala-predominant (60%) LB-pathology. SAA+ rate was 22%, increasing with disease stage and age. Higher Aß burden but lower CSF p-tau181 associated with higher SAA+ rates, especially in dementia. SAA+ affected cognitive impairment in MCI and Early-AD who were already AD biomarker positive. DISCUSSION: SAA is a sensitive, specific marker for LB-pathology. Its increase in prevalence with age and AD stages, and its association with AD biomarkers, highlights the clinical importance of α-synuclein co-pathology in understanding AD's nature and progression. HIGHLIGHTS: SAA shows 79% sensitivity, 97% specificity for LB-pathology detection in AD. SAA positivity prevalence increases with disease stage and age. Higher Aß burden, lower CSF p-tau181 linked with higher SAA+ rates in dementia. SAA+ impacts cognitive impairment in early disease stages. Study underpins need for wider LB-pathology screening in AD treatment.

19.
Sci Rep ; 14(1): 11845, 2024 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-38782941

RESUMEN

Tardigrades are renowned for their ability to survive a wide array of environmental stressors. In particular, tardigrades can curl in on themselves while losing a significant proportion of their internal water content to form a structure referred to as a tun. In surviving varying conditions, tardigrades undergo distinct morphological transformations that could indicate different mechanisms of stress sensing and tolerance specific to the stress condition. Methods to effectively distinguish between morphological transformations, including between tuns induced by different stress conditions, are lacking. Herein, an approach for discriminating between tardigrade morphological states is developed and utilized to compare sucrose- and CaCl2-induced tuns, using the model species Hypsibius exemplaris. A novel approach of shadow imaging with confocal laser scanning microscopy enabled production of three-dimensional renderings of Hys. exemplaris in various physiological states resulting in volume measurements. Combining these measurements with qualitative morphological analysis using scanning electron microscopy revealed that sucrose- and CaCl2-induced tuns have distinct morphologies, including differences in the amount of water expelled during tun formation. Further, varying the concentration of the applied stressor did not affect the amount of water lost, pointing towards water expulsion by Hys. exemplaris being a controlled process that is adapted to the specific stressors.


Asunto(s)
Cloruro de Calcio , Sacarosa , Animales , Cloruro de Calcio/farmacología , Microscopía Confocal/métodos , Estrés Fisiológico , Invertebrados , Microscopía Electrónica de Rastreo
20.
Violence Against Women ; : 10778012241257244, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38803299

RESUMEN

This mixed-methods secondary analysis examined VAW shelter use by 662 Canadian women abused by partners (50.5% Indigenous, 43.4% White, and 6.1% visible minority). Women who had never resided in shelters (n = 242) had less Severe Combined and Total IPV on the Composite Abuse Scale and fewer PTSD symptoms. More nonresidents worked full time and had higher incomes and no children. The 420 women residents mentioned strengths (70.4%) such as supportive staff and safety, and concerns (29.6%) about unsupportive staff and the shelter rules or facility. Some Indigenous women reported racist attitudes by shelter staff and child apprehensions. Practice implications are presented.

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