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Backgrounds: Family caregivers (FCs) play an essential role in delivering home-based end-of-life care. However, little is known about FCs'' experiences when undertaking this role. The integrated community end-of-life support team (ICEST) is a needs-driven, home-based, family-centered care model in Hong Kong. We evaluated its effects on FCs and compared outcomes for spouses and adult children. Method: A multicenter pre-post-test study was conducted. Eligible participants were primary FCs of terminally ill older adults (age ≥ 60) who had a life expectancy of ≤12 months. Baseline (T0) and three-month post-intervention (T1) outcome measures included FCs'' caregiving strain, psychological distress, perceived external support, intimate relationships, and communications regarding care planning. Results: A sample of 628 FCs were enrolled at T0, and 40.0% completed the T1 assessments. The ICEST model was effective in reducing caregiving strain, depression, and worries about patients, whilst there were improvements in agreement about care planning with patients, and perceived external supports. At T0, spouses held more negative perceptions of caregiving and faced fewer adjustment demands than adult children. Compared with spouses, adult children were more intimate with patients. Between T0 and T1, spouses experienced a greater reduction in worries about patients, than adult children. Conclusions: The ICEST model contributed to better outcomes, individually and relationally, for FCs, regardless of relationship type. Spouses and adult children faced different challenges while delivering home-based end-of-life care. Effective interventions should modify the negative perceptions of caregiving in spousal caregivers and enable adult children to deal with multiple tasks and complex expectations.
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BACKGROUND: Co-use of nicotine, alcohol and/or cannabis is common among adults in the United States. Co-use may represent greater addiction severity than single substance use. Recent studies have examined the extent to which the frequency, order, simultaneity, motivations, and contextual factors associated with co-use differ from that of single use. Co-use has become prevalent among racial/ethnic minority individuals who exhibit distinct co-use patterns and related outcomes; however, most of these studies rely on cross-sectional or sparse longitudinal observations. Ecological momentary assessment (EMA) can illuminate such patterns and associations with time-varying contexts. This review summarizes EMA studies on co-use published from 2008 to 2023 involving racial/ethnic minority individuals and point to gaps. Our review addresses: 1) whether use of one substance leads to substitution or complementary use of another, 2) whether antecedents/contexts differ by co-use patterns and minority status, and 3) what consequences of co-use have been documented across co-use patterns or minority status. METHODS: Search results yielded 465 articles, with 33 meeting inclusion criteria. We extracted study-level characteristics and synthesized the findings. RESULTS: The findings largely focused on co-use patterns, categories of co-use, proximal antecedents and contexts, and consequences. Variations by minority status were rarely examined; few examined acute effects of unique experiences that may contribute to co-use among racial/ethnic minority adults. CONCLUSIONS: The EMA literature on co-use is burgeoning in recent years and supports complementary hypothesis. More research to capture time-intensive data on experiences to contextualize the co-use among racial/ethnic minority groups with greater diversity in race/ethnicity is warranted.
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Consumo de Bebidas Alcoólicas , Avaliação Momentânea Ecológica , Minorias Étnicas e Raciais , Uso da Maconha , Tabagismo , Humanos , Consumo de Bebidas Alcoólicas/etnologia , Uso da Maconha/etnologia , Tabagismo/etnologiaRESUMO
Reactivation of BK polyomavirus (BKPyV) can cause significant kidney and bladder disease in immunocompromised patients. There are currently no effective, BKPyV-specific therapies. MAU868 is a novel, human immunoglobulin (Ig) G1 monoclonal antibody that binds the major capsid protein, VP1, of BKPyV with picomolar affinity, neutralizes infection by the 4 major BKPyV genotypes (EC50 ranging from 0.009-0.093 µg/mL; EC90 ranging from 0.102-4.160 µg/mL), and has comparable activity against variants with highly prevalent VP1 polymorphisms. No resistance-associated variants were identified in long-term selection studies, indicating a high in vitro barrier-to-resistance. The high-resolution crystal structure of MAU868 in complex with VP1 pentamer identified 3 key contact residues in VP1 (Y169, R170, and K172). A first-in-human study was conducted to assess the safety, tolerability, and pharmacokinetics of MAU868 following intravenous and subcutaneous administration to healthy adults in a randomized, placebo-controlled, double-blinded, single ascending dose design. MAU868 was safe and well-tolerated. All adverse events were grade 1 and resolved. The pharmacokinetics of MAU868 was typical of a human IgG, with dose-proportional systemic exposure and an elimination half-life ranging between 23 and 30 days. These results demonstrate the potential of MAU868 as a first-in-class therapeutic agent for the treatment or prevention of BKPyV disease.
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BACKGROUND: Even though racism is pervasive, some people of color may deny experiencing racial discrimination or may report being unaffected by it. This study examines the contexts and factors that may contribute to these responses among people who use substances. METHODS: We conducted seven focus groups (5-9 participants per group, total N = 43) among Black, Latino, and Asian American adults between the ages of 21 to 44 years old who reported current use of two or more of the following substances: alcohol, cigarettes, e-cigarettes, or cannabis. Data were analyzed using reflexive thematic analysis. RESULTS: Across all three ethno-racial groups, we found some respondents minimized or denied personal experiences of racial discrimination or hesitated to identify their experiences as racial discrimination, which in turn led to respondents to express uncertainty about seeing any sort of connection between racial discrimination and substance use. Themes included a minority comparison effect; a drowning out effect; diversity and racial composition of context; passing as White; and covertness of racism. Also, there were contradictions in accounts, and responses often depended on orienting cues. CONCLUSIONS: While researchers continue to find associations between racial discrimination and substance use, some people of color may not acknowledge this connection. Recommendations include aligning definitions of racism between academic and public/popular discourse; updating measures to keep up with the evolving forms of racism using context-specific examples; combining subjective measures of racial discrimination with objective measures of racism; and dialoguing with the public to raise awareness around how racism is defined.
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Background: Psychosocial status and patient reported outcomes (PRO) [depression and health-related quality-of-life (HRQoL)] are major health determinants. We investigated the association between depression and clinical outcomes in Chinese patients with type 2 diabetes (T2D), adjusted for PRO. Methods: Using prospective data from Hong Kong Diabetes Register (2013-2019), we estimated the hazard-ratio (HR, 95%CI) of depression (validated Patient Health Questionnaire 9 (PHQ-9) score≥7) with incident cardiovascular disease (CVD), ischemic heart disease (IHD), chronic kidney disease (CKD: eGFR<60 ml/min/1.73m2) and all-cause mortality in 4525 Chinese patients with T2D adjusted for patient characteristics, renal function, medications, self-care and HRQoL domains (mobility, self-care, usual activities, pain/discomfort, anxiety/depression measured by EQ-5D-3L) in linear-regression models. Results: In this cohort without prior events [mean ± SD age:55.7 ± 10.6, 43.7% women, median (IQR) disease duration of 7.0 (2.0-13.0) years, HbA1c, 7.2% (6.6%-8.20%), 26.4% insulin-treated], 537(11.9%) patients had depressive symptoms and 1923 (42.5%) patients had some problems with HRQoL at baseline. After 5.6(IQR: 4.4-6.2) years, 141 patients (3.1%) died, 533(11.8%) developed CKD and 164(3.6%) developed CVD. In a fully-adjusted model (model 4) including self-care and HRQoL, the aHR of depression was 1.99 (95% confidence interval CI):1.25-3.18) for CVD, 2.29 (1.25-4.21) for IHD. Depression was associated with all-cause mortality in models 1-3 adjusted for demographics, clinical characteristics and self-care, but was attenuated after adjusting for HRQoL (model 4- 1.54; 95%CI: 0.91-2.60), though HR still indicated same direction with important magnitude. Patients who reported having regular exercise (3-4 times per week) had reduced aHR of CKD [0.61 (0.41-0.89)]. Item 4 of PHQ-9 (feeling tired, little energy) was independently associated with all-cause mortality with aHR of 1.66 (1.30-2.12). Conclusion: Depression exhibits significant association with CVD, IHD, and all-cause mortality in patients with diabetes, adjusting for their HRQoL and health behaviors. Despite the association between depression and all-cause mortality attenuated after adjusting for HRQoL, the effect size remains substantial. The feeling of tiredness or having little energy, as assessed by item Q4 of the PHQ-9 questionnaire, was found to be significantly associated with an increased risk of all-cause mortality after covariate adjustments. Our findings emphasize the importance of incorporating psychiatric evaluations into holistic diabetes management.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Humanos , Feminino , Masculino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Hong Kong/epidemiologia , Depressão/complicações , Depressão/epidemiologia , Rim , Insuficiência Renal Crônica/complicações , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Medidas de Resultados Relatados pelo PacienteRESUMO
Exposure to cosmic ionizing radiation is an innate risk of the spaceflight environment that can cause DNA damage and altered cellular function. In astronauts, longitudinal monitoring of physiological systems and interactions between these systems are important to consider for mitigation strategies. In addition, assessments of sex-specific biological responses in the unique environment of spaceflight are vital to support future exploration missions that include both females and males. Here we assessed sex-specific, multi-system immune and endocrine responses to simulated cosmic radiation. For this, 24-week-old, male and female C57Bl/6J mice were exposed to simplified five-ion, space-relevant galactic cosmic ray (GCRsim) radiation at 15 and 50 cGy, to simulate predicted radiation exposures that would be experienced during lunar and Martian missions, respectively. Blood and adrenal tissues were collected at 3- and 14-days post-irradiation for analysis of immune and endocrine biosignatures and pathways. Sexually dimorphic adrenal gland weights and morphology, differential total RNA expression with corresponding gene ontology, and unique immune phenotypes were altered by GCRsim. In brief, this study offers new insights into sexually dimorphic immune and endocrine kinetics following simulated cosmic radiation exposure and highlights the necessity for personalized translational approaches for astronauts during exploration missions.
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Radiação Cósmica , Marte , Voo Espacial , Camundongos , Masculino , Feminino , Animais , Meio Ambiente Extraterreno , Caracteres Sexuais , Radiação Ionizante , Astronautas , Radiação Cósmica/efeitos adversos , ImunidadeRESUMO
Tuberculosis-associated hemophagocytic lymphohistiocytosis (TB-HLH) is a rare and life-threatening complication of tuberculosis infection. Early recognition and treatment of TB-HLH is crucial for improving outcomes. Treatment typically involves a combination of antituberculosis therapy and immunosuppressive therapy to control the immune system's overreaction. In this report, we present the case of a 53-year-old ambulance driver who was diagnosed with TB-HLH. His CT scan revealed splenic abscesses, hepatomegaly and bilateral lung consolidation. He subsequently developed multiorgan failure, including acute respiratory distress syndrome (ARDS), transaminitis and bone marrow dysfunction. The clinical course and simultaneous increase in serum ferritin raised the suspicion of HLH. His Hscore was 254, indicating a high probability of hemophagocytic syndrome. TB diagnosis was confirmed by positive endotracheal TB GeneXpert and bone marrow aspiration (BMA) which detected acid-fast bacilli organisms. The patient was promptly started on anti-TB, dexamethasone and IVIG. The patient responded well to treatment and made a full recovery without any lasting complications. This case highlights the importance of promptly recognising HLH and identifying the underlying cause. In critically ill patients, it is crucial not to delay HLH-specific treatment while working up for differential diagnosis.
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Linfo-Histiocitose Hemofagocítica , Mycobacterium tuberculosis , Esplenopatias , Tuberculose , Masculino , Humanos , Pessoa de Meia-Idade , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/complicações , Esplenopatias/complicações , Tuberculose/complicações , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Medula ÓsseaRESUMO
BACKGROUND: Just-in-time adaptive interventions (JITAIs) in mobile health are an intervention design that provides behavior change support based on an individual's changing and dynamic contextual state. However, few studies have documented how end users of JITAI technologies are involved in their development, particularly from historically marginalized families and children. Less is known for public health researchers and designers of the tensions that occur as families negotiate their needs. OBJECTIVE: We aimed to broaden our understanding of how historically marginalized families are included in co-design from a public health perspective. We sought to address research questions surrounding JITAIs; co-design; and working with historically marginalized families, including Black, Indigenous, and people of color (BIPOC) children and adults, regarding improving sun protection behaviors. We sought to better understand value tensions in parents' and children's needs regarding mobile health technologies and how design decisions are made. METHODS: We examined 2 sets of co-design data (local and web-based) pertaining to a larger study on mobile SunSmart JITAI technologies with families in Los Angeles, California, United States, who were predominantly of Latinx and multiracial backgrounds. In these co-design sessions, we conducted stakeholder analysis through perceptions of harms and benefits and an assessment of stakeholder views and values. We open coded the data and compared the developed themes using a value-sensitive design framework by examining value tensions to help organize our qualitative data. Our study is formatted through a narrative case study that captures the essential meanings and qualities that are difficult to present, such as quotes in isolation. RESULTS: We presented 3 major themes from our co-design data: different experiences with the sun and protection, misconceptions about the sun and sun protection, and technological design and expectations. We also provided value flow (opportunities for design), value dam (challenges to design), or value flow or dam (a hybrid problem) subthemes. For each subtheme, we provided a design decision and a response we ended up making based on what was presented and the kinds of value tensions we observed. CONCLUSIONS: We provide empirical data to show what it is like to work with multiple BIPOC stakeholders in the roles of families and children. We demonstrate the use of the value tension framework to explain the different needs of multiple stakeholders and technology development. Specifically, we demonstrate that the value tension framework helps sort our participants' co-design responses into clear and easy-to-understand design guidelines. Using the value tension framework, we were able to sort the tensions between children and adults, family socioeconomic and health wellness needs, and researchers and participants while being able to make specific design decisions from this organized view. Finally, we provide design implications and guidance for the development of JITAI mobile interventions for BIPOC families.
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Challenging parenting behaviour (CPB) refers to parental encouragement of behaviours where children push their own limits through engaging them engage in safe risks, such as rough-and-tumble play (Bögels & Phares, 2008). Preliminary evidence suggests that CPB reduces the risk of child anxiety however, little is known about the relationship between CPB and specific forms of anxiety disorders and the factors that influence this relationship. The present study aims to examine current maternal and paternal CPB in relation to symptoms of generalised anxiety disorder (GAD) and social anxiety disorder (SAD) in emerging adulthood, and to identify whether intolerance of uncertainty (IU) and cognitive avoidance (CA) sequentially mediate this relationship. A sample of 190 UK-based adults (aged 18-25) completed a battery of online self-report measures. Greater maternal CPB, but not paternal CPB, was found to predict lower symptoms of SAD, but not GAD. IU and CA did not sequentially mediate the relationship between CPB and symptoms of GAD or SAD. This study suggests that CPB may be associated with certain forms of anxiety disorders such as SAD, but further investigation is needed to understand the mechanisms between CPB and anxiety in young people.
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Cancer progression and mortality remain challenging because of current obstacles and limitations in cancer treatment. Continuous efforts are being made to explore complementary and alternative approaches to alleviate the suffering of cancer patients. Epidemiological and nutritional studies have indicated that consuming botanical foods is linked to a lower risk of cancer incidence and/or improved cancer prognosis after diagnosis. From these observations, a variety of preclinical and clinical studies have been carried out to evaluate the potential of botanical food products as anticancer medicines. Unfortunately, many investigations have been poorly designed, and encouraging preclinical results have not been translated into clinical success. Botanical products contain a wide variety of chemicals, making them more difficult to study than traditional drugs. In this review, with the consideration of the regulatory framework of the USFDA, we share our collective experiences and lessons learned from 20 years of defining anticancer foods, focusing on the critical aspects of preclinical studies that are required for an IND application, as well as the checkpoints needed for early-phase clinical trials. We recommend a developmental pipeline that is based on mechanisms and clinical considerations.
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Biologic sex influences the development of cardiovascular disease and modifies aldosterone (ALDO) and blood pressure (BP) phenotypes: females secrete more ALDO, and their adrenal glomerulosa cell is more sensitive to stimulation. Lysine-specific demethylase 1 (LSD1) variants in Africans and LSD1 deficiency in mice are associated with BP and/or ALDO phenotypes. This study, in 18- and 40-week-old wild type (WT) and LSD1+/- mice, was designed to determine whether (1) sex modifies ALDO biosynthetic enzymes; (2) LSD1 deficiency disrupts the effect of sex on these enzymes; (3) within each genotype, there is a positive relationship between ALDO biosynthesis (proximate phenotype), plasma ALDO (intermediate phenotype) and BP levels (distant phenotype); and (4) sex and LSD1 genotype interact on these phenotypes. In WT mice, female sex increases the expression of early enzymes in ALDO biosynthesis but not ALDO levels or systolic blood pressure (SBP). However, enzyme expressions are shifted downward in LSD1+/- females vs males, so that early enzyme levels are similar but the late enzymes are substantially lower. In both age groups, LSD1 deficiency modifies the adrenal enzyme expressions, circulating ALDO levels, and SBP in a sex-specific manner. Finally, significant sex/LSD1 genotype interactions modulate the three phenotypes in mice. In conclusion, biologic sex in mice interacts with LSD1 deficiency to modify several phenotypes: (1) proximal (ALDO biosynthetic enzymes); (2) intermediate (circulating ALDO); and (3) distant (SBP). These results provide entry to better understand the roles of biological sex and LSD1 in (1) hypertension heterogeneity and (2) providing more personalized treatment.
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Hipertensão , Lisina , Masculino , Feminino , Camundongos , Animais , Lisina/metabolismo , Lisina/farmacologia , Aldosterona/metabolismo , Pressão Sanguínea , Hipertensão/metabolismo , Zona Glomerulosa/metabolismoRESUMO
Fluorescence imaging is an indispensable method for studying biological processes non-invasively in cells and transparent organisms. Extension into the shortwave infrared (SWIR, 1000-2000 nm) region of the electromagnetic spectrum has allowed for imaging in mammals with unprecedented depth and resolution for optical imaging. In this review, we summarize recent advances in imaging technologies, dye scaffold modifications, and incorporation of these dyes into probes for SWIR imaging in mice. Finally, we offer an outlook on the future of SWIR detection in the field of chemical biology.
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Corantes Fluorescentes , Imagem Óptica , Animais , Corantes Fluorescentes/química , Mamíferos , Camundongos , Imagem Óptica/métodosRESUMO
BACKGROUND: There is a growing need for palliative care for patients near the end of life and their caregivers. Palliative and end-of-life care (EoLC) education are recommended for all health care (e.g., physicians, nurses, and allied health practitioners) and social care professionals (e.g., social workers) to ensure the quality of services. However, less attention has been afforded to generic, in contrast to specialized, EoLC education. This study evaluated the effectiveness of a series of short-term generic EoLC educational programs for health and social care professionals. METHOD: A pre-post survey design was adopted, focusing on different EoLC core competences. RESULTS: Significant improvement was observed in all perceived competences after the educational programs, regardless of participants' occupation or EoLC experience. Perceived competence in self-care was rated significantly higher than all other competences prior to the programs. Healthcare professionals rated significantly higher on competence in symptom management than social workers. Scores on communication skill and self-care competences were significantly higher following longer (i.e., 16-24 hours) than shorter (i.e., 4-8 hours) programs. CONCLUSION: Generalist palliative/EoLC educational programs may enable health and social care professionals to refresh and extend their knowledge and skills and enhance their perceived competence in providing EoLC. Further research on generalist palliative/EoLC education is needed to examine the impact of continuing training on professionals' actual practice in EoLC and palliative care.
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Cuidados Paliativos na Terminalidade da Vida , Assistência Terminal , Competência Clínica , Humanos , Cuidados Paliativos , Apoio SocialRESUMO
PURPOSE: To compare the efficacy and safety of intravitreal aflibercept (IVA) monotherapy versus aflibercept combined with reduced-fluence photodynamic therapy (RF-PDT) (IVA+RF-PDT) for the treatment of polypoidal choroidal vasculopathy (PCV). METHODS AND ANALYSIS: Multicentred, double-masked, randomised controlled trial to compare the two treatment modalities. The primary outcome of the study is to compare the 52-week visual outcome of IVA versus IVA+RF PDT. One hundred and sixty treatment-naïve patients with macular PCV confirmed on indocyanine green angiography will be recruited from three centres in Singapore. Eligible patients will be randomised (1:1 ratio) into one of the following groups: IVA monotherapy group-aflibercept monotherapy with sham photodynamic therapy (n=80); combination group-aflibercept with RF-PDT (n=80). Following baseline visit, all patients will be monitored at 4 weekly intervals during which disease activity will be assessed based on best-corrected visual acuity (BCVA), ophthalmic examination findings, optical coherence tomography (OCT) and angiography where indicated. Eyes that meet protocol-specified retreatment criteria will receive IVA and sham/RF-PDT according to their randomisation group. Primary endpoint will be assessed as change in BCVA at week 52 from baseline. Secondary endpoints will include anatomical changes based on OCT and dye angiography as well as safety assessment. Additionally, we will be collecting optical coherence tomography angiography data prospectively for exploratory analysis. ETHICS AND DISSEMINATION: This study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the ICH E6 guidelines of Good Clinical Practice and the applicable regulatory requirements. Approval from the SingHealth Centralised Institutional Review Board has been sought prior to commencement of the study. TRIAL REGISTRATION NUMBER: NCT03941587.
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Fotoquimioterapia , Pólipos , Inibidores da Angiogênese/uso terapêutico , Corioide/diagnóstico por imagem , Angiofluoresceinografia , Seguimentos , Humanos , Injeções Intravítreas , Fármacos Fotossensibilizantes/uso terapêutico , Pólipos/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Singapura , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade VisualRESUMO
BACKGROUND: Research consistently report an inverse relationship between suicide risk and help-seeking. The increasingly available internet-based support potentially offers an attractive alternative to traditional forms of assistance. The study compared the characteristics of suicidal youths in Hong Kong and their online and offline help-seeking behaviours. METHODS: Participants (N = 1214, age-range = 15-24 years) responded to the anonymous 2018 Hong Kong Online Survey on Youth Mental Health and Internet Usage. Respondents with suicidal thoughts were classified into those who sought help online and offline, or online only ("online-help"); those who sought help offline only ("offline-help"); and those who never sought help ("no-help"). They responded to questions concerning mental health, perception towards online support, internet use, help sources, and demographic information. RESULTS: The online-help group differed significantly from other groups, with greater suicidal ideation, distress, risk behaviours, and spent more time online for non-work-related purposes. Their perceived benefits of online support include anonymity, avoiding embarrassment, and social support. They are more likely to seek help from a combination of informal and formal sources. LIMITATIONS: No data on whether participants sought help online or offline first, and their current treatment status is available. Our study adopted conveniences sampling, and few respondents have sought help online exclusively. CONCLUSION: Online support offers an alternate way of engaging at-risk youths. Future clinical practice should consider online platforms as a complement, rather than a replacement, of offline platforms.
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Comportamento de Busca de Ajuda , Suicídio , Adolescente , Adulto , Hong Kong , Humanos , Internet , Saúde Mental , Apoio Social , Ideação Suicida , Inquéritos e Questionários , Adulto JovemRESUMO
Biophysical cues in the extracellular matrix (ECM) regulate cell behavior in a complex, nonlinear, and interdependent manner. To quantify these important regulatory relationships and gain a comprehensive understanding of mechanotransduction, there is a need for high-throughput matrix platforms that enable parallel culture and analysis of cells in various matrix conditions. Here we describe a multiwell hyaluronic acid (HA) platform in which cells are cultured on combinatorial arrays of hydrogels spanning a range of elasticities and adhesivities. Our strategy utilizes orthogonal photopatterning of stiffness and adhesivity gradients, with the stiffness gradient implemented by a programmable light illumination system. The resulting platform allows individual treatment and analysis of each matrix environment while eliminating contributions of haptotaxis and durotaxis. In human mesenchymal stem cells, our platform recapitulates expected relationships between matrix stiffness, adhesivity, and cell mechanosensing. We further applied the platform to show that as integrin ligand density falls, cell adhesion and migration depend more strongly on CD44-mediated interactions with the HA backbone. We anticipate that our system could bear great value for mechanistic discovery and screening where matrix mechanics and adhesivity are expected to influence phenotype.
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Hidrogéis , Mecanotransdução Celular , Adesão Celular , Matriz Extracelular , Humanos , Ácido HialurônicoRESUMO
The claustrum is a thin sheet of neurons that is densely connected to many cortical regions and has been implicated in numerous high-order brain functions. Such brain functions arise from brain states that are influenced by neuromodulatory pathways from the cholinergic basal forebrain, dopaminergic substantia nigra and ventral tegmental area, and serotonergic raphe. Recent revelations that the claustrum receives dense input from these structures have inspired investigation of state-dependent control of the claustrum. Here, we review neuromodulation in the claustrum-from anatomical connectivity to behavioral manipulations-to inform future analyses of claustral function.
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Claustrum , Dopamina , Neurônios , Substância Negra , Área Tegmentar VentralRESUMO
INTRODUCTION: This study reviews malpractice, also called medical professional liability (MPL), claims involving adult patients cared for in emergency departments (ED) and urgent care settings. METHODS: We conducted a retrospective review of closed MPL claims of adults over 18 years, from the Medical Professional Liability Association's Data Sharing Project database from 2001-2015, identifying 6,779 closed claims. Data included the total amount, origin, top medical specialties named, chief medical factors, top medical conditions, severity of injury, resolution, average indemnity, and defense costs of closed claims. RESULTS: Of 6,779 closed claims, 65.9% were dropped, withdrawn, or dismissed. Another 22.8% of claims settled for an average indemnity of $297,709. Of the 515 (7.6%) cases that went to trial, juries returned verdicts for the defendant in 92.6% of cases (477/515). The remaining 7.4% of cases (38/515) were jury verdicts for the plaintiff, with an average indemnity of $816,909. The most common resulting medical condition cited in paid claims was cardiac or cardiorespiratory arrest (10.4%). Error in diagnosis was the most common chief medical error cited in closed claims. Death was the most common level of severity listed in closed (38.5%) and paid (42.8%) claims. Claims reporting major permanent injury had the highest paid-to-closed ratio, and those reporting grave injury had the highest average indemnity of $686,239. CONCLUSION: This retrospective review updates the body of knowledge surrounding medical professional liability and represents the most recent analysis of claims in emergency medicine. As the majority of emergency providers will be named in a MPL claim during their career, it is essential to have a better understanding of the most common factors resulting in MPL claims.
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Assistência Ambulatorial , Serviços Médicos de Emergência , Medicina de Emergência , Serviço Hospitalar de Emergência , Imperícia , Adulto , Assistência Ambulatorial/legislação & jurisprudência , Assistência Ambulatorial/métodos , Serviços Médicos de Emergência/legislação & jurisprudência , Serviços Médicos de Emergência/métodos , Serviço Hospitalar de Emergência/economia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Revisão da Utilização de Seguros , Responsabilidade Legal/economia , Masculino , Imperícia/legislação & jurisprudência , Imperícia/estatística & dados numéricos , Imperícia/tendências , Estudos Retrospectivos , Estados UnidosRESUMO
BACKGROUND: In Alzheimer's disease, accumulation of beta amyloid (Aß) triggers amyloidogenesis and hyperphosphorylation of tau protein leading to neuronal cell death. Piper sarmentosum Roxb. (PS) is a traditional medicinal herb used by Malay to treat rheumatism, headache and boost memory. It possesses various biological effects, such as anti-cholinergic, anti-inflammatory, anti-oxidant and anti-depressant-like effects. OBJECTIVE: The present study aimed to investigate neuroprotective properties of PS against Aß-induced neurotoxicity and to evaluate its potential mechanism of action. METHODS: Neuroprotective effects of hexane (HXN), dichloromethane (DCM), ethyl acetate (EA) and methanol (MEOH) extracts from leaves (L) and roots (R) of PS against Aß-induced neurotoxicity were investigated in SH-SY5Y human neuroblastoma cells. Cells were pre-treated with PS for 24 h followed by 24 h of induction with Aß. The neuroprotective effects of PS were studied using cell viability and cellular reactive oxygen species (ROS) assays. The levels of extracellular Aß and tau proteins phosphorylated at threonine 231 (pT231) were determined. Gene and protein expressions were assessed using qRT-PCR analyses and western blot analyses, respectively. RESULTS: Hexane extracts of PS (LHXN and RHXN) protected SH-SY5Y cells against Aß-induced neurotoxicity, and decreased levels of extracellular Aß and phosphorylated tau (pT231). Although extracts of PS inhibited Aß-induced ROS production, it was unlikely that neuroprotective effects were simply due to the anti-oxidant capacity of PS. Further, mechanistic study suggested that the neuroprotective effects of PS might be due to its capability to regulate amyloidogenesis through the downregulation of BACE and APP. CONCLUSION: These findings suggest that hexane extracts of PS confer neuroprotection against Aß- induced neurotoxicity in SH-SY5Y cells by attenuating amyloidogenesis and tau hyperphosphorylation. Due to its neuroprotective properties, PS might be a potential therapeutic agent for Alzheimer's disease.
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INTRODUCTION: Voters facing illness or disability are disproportionately under-represented in terms of voter turnout. Earlier research has indicated that enfranchisement of these populations may reinforce the implementation of policies improving health outcomes and equity. Due to the confluence of the coronavirus 2019 (COVID-19) pandemic and the 2020 election, we aimed to assess emergency absentee voting processes, which allow voters hospitalized after regular absentee deadlines to still obtain an absentee ballot, and election changes due to COVID-19 in all 50 states. METHODS: We performed a cross-sectional study collecting 34 variables pertaining to emergency voting processes and COVID-19-related election changes, including deadlines, methods of submission for applications and ballots, and specialized services for patients. Data were obtained from, in order of priority, state boards of elections websites, poll worker manuals, application forms, and state legislation. We verified all data through direct correspondence with state boards of elections. RESULTS: Emergency absentee voting processes are in place in 39 states, with the remaining states having universal vote-by-mail (n = 5) or extended regular absentee voting deadlines (n = 6). The emergency absentee period most commonly began within 24 hours following the normal absentee application deadline, which was often seven days before an election (n = 11). Unique aspects of emergency voting processes included patients designating an "authorized agent" to deliver their applications and ballots (n = 38), electronic ballot delivery (n = 5), and in-person teams that deliver ballots directly to patients (n = 18). Documented barriers in these processes nationwide include unavailable online information (n = 11), restrictions mandating agents to be family members (n = 7), physician affidavits or signatures (n = 9), and notary or witness signature requirements (n = 15). For the November 2020 presidential election, 12 states expanded absentee eligibility to allow COVID-19 as a reason to request an absentee ballot, and 18 states mailed absentee ballot applications or absentee ballots to all registered voters. CONCLUSION: While 39 states operate emergency absentee voting processes for hospitalized voters, there are considerable areas for improvement and heterogeneity in guidelines for these protocols. For future election cycles, information on emergency voting and broader election reforms due to COVID-19 may be useful for emergency providers and patients alike to improve the democratic participation of voters experiencing illness.