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Addressing Indigenous rights and interests in genetic resources has become increasingly challenging in an open science environment that promotes unrestricted access to genomic data. Although Indigenous experiences with genetic research have been shaped by a series of negative interactions, there is increasing recognition that equitable benefits can only be realized through greater participation of Indigenous communities. Issues of trust, accountability and equity underpin Indigenous critiques of genetic research and the sharing of genomic data. This Perspectives article highlights identified issues for Indigenous communities around the sharing of genomic data and suggests principles and actions that genomic researchers can adopt to recognize community rights and interests in data.
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Privacidad Genética/ética , Genómica/ética , Pueblos Indígenas/genética , Difusión de la Información/ética , Acceso a la Información , Investigación Genética/ética , Genoma Humano/genética , Derechos Humanos , HumanosRESUMEN
The field of genomics has benefited greatly from its "openness" approach to data sharing. However, with the increasing volume of sequence information being created and stored and the growing number of international genomics efforts, the equity of openness is under question. The United Nations Convention of Biodiversity aims to develop and adopt a standard policy on access and benefit-sharing for sequence information across signatory parties. This standardization will have profound implications on genomics research, requiring a new definition of open data sharing. The redefinition of openness is not unwarranted, as its limitations have unintentionally introduced barriers of engagement to some, including Indigenous Peoples. This commentary provides an insight into the key challenges of openness faced by the researchers who aspire to protect and conserve global biodiversity, including Indigenous flora and fauna, and presents immediate, practical solutions that, if implemented, will equip the genomics community with both the diversity and inclusivity required to respectfully protect global biodiversity.
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Pueblos Indígenas/genética , Difusión de la Información/ética , Biodiversidad , Genómica/métodos , Humanos , Pueblos Indígenas/psicología , Pueblos Indígenas/estadística & datos numéricos , Difusión de la Información/métodos , Grupos de Población/genéticaRESUMEN
BACKGROUND: Hepatic steatosis is a major cause of chronic liver disease associated with several negative health outcomes. We compared the prevalence of and factors associated with steatosis in people living with and without HIV. METHODS: Older (>50 years) and younger (<50 years) people with HIV and older HIV-negative controls (>50 years) underwent liver transient elastography examination with controlled attenuation parameter (steatosis ≥238 dB/m, moderate/severe steatosis ≥280 dB/m, liver fibrosis ≥7.1 kPa). We compared groups using logistic regression/Chi-squared/Fisher's exact/Kruskal-Wallis tests. RESULTS: In total, 317 participants (109 older people with HIV; 101 younger people with HIV; 107 HIV-negative controls) were predominantly white (86%) and male (76%), and 21% were living with obesity (body mass index ≥30 kg/m2 ). Most (97%) people with HIV had undetectable HIV RNA. The prevalence of fibrosis was 8.4%, 3.0%, and 6.5% in the three groups, respectively (p = 0.26). Fibrosis was predominately (>65%) mild. The prevalence of steatosis was the same in older people with HIV (66.4%) and controls (66.4%) but lower in younger people with HIV (37.4%; p < 0.001). After adjustment, younger people with HIV were less likely to have steatosis (odds ratio [OR] 0.26; 95% confidence interval [CI] 0.14-0.52) than controls, but male sex (OR 2.45; 95% CI 1.20-4.50) and high waist-to-hip ratio (OR 3.04; 95% CI 1.74-5.33) were associated with an increased odds of steatosis. We found no association between steatosis and HIV-related variables. CONCLUSIONS: The prevalence of hepatic steatosis and fibrosis was similar between older participants regardless of HIV status. Age, sex, and abdominal obesity, but not HIV-related variables, were associated with steatosis. Interventions for controlling obesity should be integrated into routine HIV care.
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Diagnóstico por Imagen de Elasticidad , Hígado Graso , Infecciones por VIH , Papaver , Humanos , Masculino , Anciano , Estudios Transversales , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Infecciones por VIH/patología , Hígado Graso/epidemiología , Hígado Graso/patología , Hígado/diagnóstico por imagen , Cirrosis Hepática/epidemiología , Cirrosis Hepática/complicaciones , Obesidad/complicaciones , Obesidad/epidemiología , Diagnóstico por Imagen de Elasticidad/efectos adversosRESUMEN
INTRODUCTION: Non-cognitive traits should be considered when selecting candidates to study medicine. However, evaluating these traits remains difficult. We explored whether measuring undesirable non-cognitive behaviour ('Red Flags') added value to a medical school admissions system. Red Flags included rudeness, ignoring the contributions of others, disrespectful behaviour, or poor communication. METHODS: Following an admissions interview testing non-cognitive attributes in 648 applicants to a UK medical school, we measured the association between interview score and Red Flag frequency. We tested linear and polynomial regression models to evaluate whether the association was linear or non-linear. RESULTS: In total, 1126 Red Flags were observed. While Red Flags were concentrated among low-scorers, candidates in the highest- and second-highest deciles for interview score still received Red Flags (six and twenty-two, respectively). The polynomial regression model indicated candidates with higher scores received fewer Red Flags, but the association was not linear (F(3644) = 159.8, p = .001, adjusted R2 = 0.42). CONCLUSIONS: The non-linear association between interview score and Red Flag frequency shows some candidates with desirable non-cognitive attributes will still display undesirable-or even exclusionary-non-cognitive attributes. Recording Red Flag behaviour reduces the likelihood such candidates will be offered a place at medical school.
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Medicina , Facultades de Medicina , Humanos , Criterios de Admisión EscolarRESUMEN
BACKGROUND: Tenecteplase (TNK) is emerging as an alternative to alteplase (ALT) for thrombolytic treatment of acute ischemic stroke (AIS). Compared to ALT, TNK has a longer half-life, shorter administration time, lower cost, and similarly high efficacy in treating large vessel occlusion. Nevertheless, there are barriers to adopting TNK as a treatment for AIS. This study aimed to identify thematic barriers and facilitators to adopting TNK as an alternative to ALT as a thrombolytic for eligible AIS patients. METHODS: Qualitative research methodology using hermeneutic cycling and purposive sampling was used to interview four stroke clinicians in Texas. Interviews were recorded and transcribed verbatim. Enrollment was complete when saturation was reached. All members of the research team participated in content analysis during each cycle and in thematic analysis after saturation. RESULTS: Interviews were conducted between November 2022 and February 2023 with stroke center representatives from centers that either had successfully adopted TNK, or had not yet adopted TNK. Three themes and eight sub-themes were identified. The theme "Evidence" had three sub-themes: Pro-Con Balance, Fundamental Knowledge, and Pharmacotherapeutics. The theme "Process Flow" had four subthemes: Proactive, Reflective self-doubt, Change Process Barriers, and Parameter Barriers. The theme "Consensus" had one sub-theme: Getting Buy-In. CONCLUSION: Clinicians experience remarkably similar barriers and facilitators to adopting TNK. The results lead to a hypothesis that providing evidence to support a practice change, and identifying key change processes, will help clinicians achieve consensus across teams that need to 'buy in' to adopting TNK for AIS treatment.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Tenecteplasa/efectos adversos , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Resultado del Tratamiento , Activador de Tejido Plasminógeno/efectos adversos , Fibrinolíticos/efectos adversos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/tratamiento farmacológico , Investigación CualitativaRESUMEN
BACKGROUND: Tenecteplase (TNK) is gaining recognition as a novel therapy for acute ischemic stroke (AIS). Despite TNK offering a longer half-life, time and cost saving benefits and comparable treatment and safety profiles to Alteplase (ALT), the adoption of TNK as a treatment for AIS presents challenges for hospital systems. OBJECTIVE: Identify barriers and facilitators of TNK implementation at acute care hospitals in Texas. METHODS: This prospective survey used open-ended questions and Likert statements generated from content experts and informed by qualitative research. Stroke clinicians and nurses working at 40 different hospitals in Texas were surveyed using a virtual platform. RESULTS: The 40 hospitals had a median of 34 (IQR 24.5-49) emergency department beds and 42.5 (IQR 23.5-64.5) inpatient stroke beds with 506.5 (IQR 350-797.5) annual stroke admissions. Fifty percent of the hospitals were Comprehensive Stroke Centers, and 18 (45 %) were solely using ALT for treatment of eligible AIS patients. Primary facilitators to TNK transition were team buy-in and a willingness of stroke physicians, nurses, and pharmacists to adopt TNK. Leading barriers were lack of clinical evidence supporting TNK safety profile inadequate evidence supporting TNK use and a lack of American Heart Association guidelines support for TNK administration in all AIS cases. CONCLUSION: Understanding common barriers and facilitators to TNK adoption can assist acute care hospitals deciding to implement TNK as a treatment for AIS. These findings will be used to design a TNK adoption Toolkit, utilizing implementation science techniques, to address identified obstacles and to leverage facilitators.
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Accidente Cerebrovascular Isquémico , Tenecteplasa , Humanos , Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Estudios Prospectivos , Tenecteplasa/uso terapéutico , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Tenecteplase (TNK) is considered a promising option for the treatment of acute ischemic stroke (AIS) with the potential to decrease door-to-needle times (DTN). This study investigates DTN metrics and trends after transition to tenecteplase. METHODS: The Lone Star Stroke (LSS) Research Consortium TNK registry incorporated data from three Texas hospitals that transitioned to TNK. Subject data mapped to Get-With-the-Guidelines stroke variables from October 1, 2019 to March 31, 2023 were limited to patients who received either alteplase (ALT) or TNK within the 90 min DTN times. The dataset was stratified into ALT and TNK cohorts with univariate tables for each measured variable and further analyzed using descriptive statistics. Logistic regression models were constructed for both ALT and TNK to investigate trends in DTN times. RESULTS: In the overall cohort, the TNK cohort (n = 151) and ALT cohort (n = 161) exhibited comparable population demographics, differing only in a higher prevalence of White individuals in the TNK cohort. Both cohorts demonstrated similar clinical parameters, including mean NIHSS, blood glucose levels, and systolic blood pressure at admission. In the univariate analysis, no difference was observed in median DTN time within the 90 min time window compared to the ALT cohort [40 min (30-53) vs 45 min (35-55); P = .057]. In multivariable models, DTN times by thrombolytic did not significantly differ when adjusting for NIHSS, age (P = .133), or race and ethnicity (P = .092). Regression models for the overall cohort indicate no significant DTN temporal trends for TNK (P = .84) after transition; nonetheless, when stratified by hospital, a single subgroup demonstrated a significant DTN upward trend (P = 0.002). CONCLUSION: In the overall cohort, TNK and ALT exhibited comparable temporal trends and at least stable DTN times. This indicates that the shift to TNK did not have an adverse impact on the DTN stroke metrics. This seamless transition is likely attributed to the similarity of inclusion and exclusion criteria, as well as the administration processes for both medications. When stratified by hospital, the three subgroups demonstrated variable DTN time trends which highlight the potential for either fatigue or unpreparedness when switching to TNK. Because our study included a multi-ethnic cohort from multiple large Texas cities, the stable DTN times after transition to TNK is likely applicable to other healthcare systems.
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Fibrinolíticos , Accidente Cerebrovascular Isquémico , Sistema de Registros , Tenecteplasa , Terapia Trombolítica , Tiempo de Tratamiento , Humanos , Texas/epidemiología , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Masculino , Femenino , Factores de Tiempo , Anciano , Tiempo de Tratamiento/tendencias , Tenecteplasa/uso terapéutico , Tenecteplasa/administración & dosificación , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/diagnóstico , Terapia Trombolítica/tendencias , Terapia Trombolítica/efectos adversos , Persona de Mediana Edad , Resultado del Tratamiento , Anciano de 80 o más Años , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/efectos adversosRESUMEN
Over the past few decades, the life expectancy of people living with HIV has markedly improved due to the advances in HIV diagnosis, linkage to care, and treatment. However, with these advances, a new set of challenges has emerged that must be addressed to ensure the long-term well-being of people living with HIV. In this article, as part of a wider journal supplement, we explore the unmet needs and challenges across the HIV continuum of care and re-define what long-term success looks like to support the healthy ageing of all people affected by HIV.
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Continuidad de la Atención al Paciente , Infecciones por VIH , Humanos , Infecciones por VIH/terapia , Calidad de Vida , Envejecimiento SaludableRESUMEN
OBJECTIVES: In recent decades, the needs of people living with HIV have evolved as life expectancy has greatly improved. Now, a new definition of long-term success (LTS) is necessary to help address the multifaceted needs of all people living with HIV. METHODS: We conducted a two-phase research programme to delineate the range of experiences of people living with HIV. The insights garnered from these research phases were explored in a series of expert-led workshops, which led to the development and refinement of the LTS framework. RESULTS: The insights generated from the research phases identified a series of themes that form a part of LTS. These themes were subsequently incorporated into the LTS framework, which includes five outcome pillars: sustained undetectable viral load, minimal impact of treatment and clinical monitoring, optimized health-related quality of life, lifelong integration of healthcare, and freedom from stigma and discrimination. A series of supporting statements were also developed by the expert panel to help in the achievement of each of the LTS pillars. CONCLUSIONS: The LTS framework offers a comprehensive and person-centric approach that, if achieved, could help improve the long-term well-being of people living with HIV and support the LTS vision of 'every person living with HIV being able to live their best life'.
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Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Calidad de Vida , Estigma SocialRESUMEN
BACKGROUND: Anticholinergic medications (ACMs) are associated with poorer age-related outcomes, including falls and frailty. We investigate associations between ACM use and recurrent falls and frailty among older (aged ≥50 years) people with HIV in the POPPY study. METHODS: Anticholinergic potential of co-medications at study entry was coded using the anticholinergic burden score, anticholinergic risk score, and Scottish Intercollegiate Guidelines Network score; drugs scoring ≥1 on any scale were defined as ACM. Associations with recurrent falls (two or more falls in the previous 28 days) and frailty (modified Fried's) were assessed using logistic regression adjusting for (1) possible demographic/lifestyle confounders and (2) clinical factors and depressive symptoms (Patient Health Questionnaire-9). RESULTS: ACM use was reported by 193 (28%) of 699 participants, with 64 (9%) receiving two or more ACM; commonly prescribed ACMs were codeine (12%), citalopram (12%), loperamide (9%), and amitriptyline (7%). Falls were reported in 63/673 (9%), and 126/609 (21%) met the frailty criteria. Both recurrent falls and frailty were more common in ACM users than in non-users (recurrent falls: 17% in users vs. 6% in non-users, p < 0.001; frailty: 32% vs. 17%, respectively, p < 0.001). Use of two or more ACMs was associated with increased odds of falls after adjustment for demographic/lifestyle factors (odds ratio [OR] 4.53; 95% confidence interval [CI] 2.06-9.98) and for clinical factors (OR 3.58; 95% CI 1.37-9.38). Similar albeit weaker associations were seen with frailty (OR 2.26; 95% CI 1.09-4.70 and OR 2.12; 95% CI 0.89-5.0, respectively). CONCLUSIONS: ACM are commonly prescribed for people living with HIV, and evidence exists for an association with recurrent falls and frailty. Clinicians should be alert to this and reduce ACM exposure where possible.
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Fragilidad , Infecciones por VIH , Humanos , Fragilidad/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Factores de Riesgo , Antagonistas Colinérgicos/efectos adversosRESUMEN
BACKGROUND: We aimed to create a multidisciplinary consensus clinical guideline for best practice in the diagnosis, investigation and management of spontaneous intracranial hypotension (SIH) due to cerebrospinal fluid leak based on current evidence and consensus from a multidisciplinary specialist interest group (SIG). METHODS: A 29-member SIG was established, with members from neurology, neuroradiology, anaesthetics, neurosurgery and patient representatives. The scope and purpose of the guideline were agreed by the SIG by consensus. The SIG then developed guideline statements for a series of question topics using a modified Delphi process. This process was supported by a systematic literature review, surveys of patients and healthcare professionals and review by several international experts on SIH. RESULTS: SIH and its differential diagnoses should be considered in any patient presenting with orthostatic headache. First-line imaging should be MRI of the brain with contrast and the whole spine. First-line treatment is non-targeted epidural blood patch (EBP), which should be performed as early as possible. We provide criteria for performing myelography depending on the spine MRI result and response to EBP, and we outline principles of treatments. Recommendations for conservative management, symptomatic treatment of headache and management of complications of SIH are also provided. CONCLUSIONS: This multidisciplinary consensus clinical guideline has the potential to increase awareness of SIH among healthcare professionals, produce greater consistency in care, improve diagnostic accuracy, promote effective investigations and treatments and reduce disability attributable to SIH.
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Hipotensión Intracraneal , Humanos , Hipotensión Intracraneal/diagnóstico , Hipotensión Intracraneal/terapia , Pérdida de Líquido Cefalorraquídeo/diagnóstico , Pérdida de Líquido Cefalorraquídeo/terapia , Pérdida de Líquido Cefalorraquídeo/complicaciones , Imagen por Resonancia Magnética/efectos adversos , Cefalea/diagnóstico , Cefalea/etiología , Cefalea/terapia , Diagnóstico DiferencialRESUMEN
IMPORTANCE: Actinic keratosis (AK) is a premalignant lesion that has a1% to 10% potential of progression to squamous cell carcinoma (SCC), but it is not possible to determine which lesions are at higher risk. OBJECTIVE: This study examined the epidermal genetic profiles of actinic keratosis and SCC through non-invasive techniques seeking to develop a biopsy-free method for AK monitoring and aid in the early diagnosis of developing SCC. DESIGN: Ribonucleic acid (RNA) was collected from adhesive tape strips and gene expression levels were measured. A threshold fold change >2 and adjusted P-value <0.05 were used to determine differentially expressed genes. SETTING: Single center dermatology clinic. PARTICIPANTS: Patients who presented to the clinic with lesions suspicious of non-melanoma skin cancer that had never been previously biopsied. MAIN OUTCOME AND MEASURE: RNA was extracted via non-invasive biopsy and sequenced. Low quality samples were filtered out and the remaining samples underwent differential gene expression analysis by DESeq2 in R package. A threshold of fold change >2 and adjusted P-value <0.05 was used for determination of differentially expressed genes. The differentially expressed genes that overlapped between the corrected and uncorrected groups were the most significant for analysis. RESULTS: From 47 lesions, 6 significant differentially expressed genes were found between AK and SCC, and 25 significant differentially expressed genes between in-situ SCC and invasive SCC. Individual samples showed similarities based on diagnosis, suggesting mutations were specific to the disease and not the individual. CONCLUSIONS AND RELEVANCE: These findings highlight which genes may play a role in AK progression to SCC. The genomic differences between in-situ and invasive squamous cell carcinoma open an opportunity for early diagnosis of squamous cell carcinoma and risk prediction of actinic keratosis. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7097.
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Carcinoma de Células Escamosas , Queratosis Actínica , Neoplasias Cutáneas , Humanos , Queratosis Actínica/diagnóstico , Queratosis Actínica/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Epidermis/patología , ARNRESUMEN
BACKGROUND: Ultraviolet (UV) radiation leads to deoxyribonucleic acid (DNA) damage and changes in gene expression. Topical DNA repair enzymes in liposomes are capable of undoing this damage. OBJECTIVE: To evaluate gene expression changes induced by ultraviolent B-rays (UVB) light and assess the effect of topical DNA repair enzymes extracted from Micrococcus luteus (M. luteus) and photolyase in modifying these changes. METHODS: Non-invasive, adhesive patch collection kits were used to sample skin on the right and left post-auricular areas before and 24 hours after UVB exposure (n=48). Subjects applied topical DNA repair enzymes to the right post-auricular area daily for 2 weeks. Subjects returned 2 weeks later for repeat non-invasive skin sample collection. RESULTS: Eight of 18 tested genes demonstrated significant changes 24 hours following UVB exposure. DNA repair enzymes from M. luteus or photolyase had no significant effect on genetic expression compared with the control at 2 weeks post UV exposure. CONCLUSION: UVB exposure causes acute changes in gene expression, which may play roles in photo-aging damage and skin cancer growth and regulation. While non-invasive gene expression testing can detect UV damage, additional genomic studies investigating recovery from UV damage at different time periods are needed to establish the potential of DNA repair enzymes to minimize or reverse this damage. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7070.
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Desoxirribodipirimidina Fotoliasa , Neoplasias Cutáneas , Humanos , Daño del ADN , Desoxirribodipirimidina Fotoliasa/genética , Reparación del ADN , Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Enzimas Reparadoras del ADN/genéticaRESUMEN
Previous research has documented the various challenges people living with HIV face as they navigate intimate relationships, including what is often referred to as disclosure. In studies of gay, bisexual and other men who have sex with men, the issue of telling or not telling others about an HIV-positive status has been examined primarily in relation to communication with sexual partners, with few studies focusing on other aspects of intimacy. Drawing on interviews with gay men living with HIV, conducted in four clinics in London, this article explores the narratives of men who have been asked by female friends about the possibility of being a sperm donor. The narratives highlight layers of complexity which have received little attention, not only in research on HIV but also in studies of sperm donation and co-parenting. The article advances dialogue between these two largely separate bodies of work. Our data suggest that reluctance to share an HIV-positive status with others can be an important factor in deciding how to answer the 'sperm donor question'. Examining reproductive relationships of a specific kind - those based on friendships between women and gay men - the article develops the understanding of how secrecy about HIV shapes intimate lives.
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INTRODUCTION: This short report describes the results of a survey that was developed by Public Health England (PHE), the British HIV Association (BHIVA) and the Children's HIV Association (CHIVA) and circulated to all UK national health service HIV providers in the UK following the first wave of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus disease 2019 [COVID-19]) pandemic to assess the impact of the pandemic on HIV clinics. METHODS: The survey was created by BHIVA/CHIVA and PHE and was piloted prior to circulation to all HIV clinics within the UK on 3 July 2020. The survey questions were designed to assess the impact of the first wave of COVID-19 on HIV clinics and lead/senior HIV clinicians. Clinicians' responses were collected between 3 July 2020 and 17 September 2020. The survey responses were collated, and non-statistical analysis was performed. RESULTS: The results of the survey confirmed that services had undergone substantial changes, including a shift from face-to-face consults to predominantly virtual consultations. Some clinicians' responses suggested that the first wave had many negative effects on people living with HIV, including their ability to access mental health services. CONCLUSION: The first wave of COVID-19 caused significant changes to HIV services within the UK. There was a shift toward the use of technology in healthcare, and results from subsequent clinician surveys carried out since the first wave of COVID-19 will reflect the ongoing transformation of care towards a more virtual service.
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COVID-19 , Infecciones por VIH , COVID-19/epidemiología , Niño , Inglaterra/epidemiología , Infecciones por VIH/epidemiología , Humanos , Salud Pública , SARS-CoV-2 , Medicina EstatalRESUMEN
Excess dietary fructose is a major public health concern, yet little is known about its influence on offspring development and later-life disease when consumed in excess during pregnancy. To determine whether increased maternal fructose intake could have long-term consequences on offspring health, we investigated the effects of 10% w/v fructose water intake during preconception and pregnancy in guinea pigs. Female Dunkin Hartley guinea pigs were fed a control diet (CD) or fructose diet (FD; providing 16% of total daily caloric intake) ad libitum 60 days prior to mating and throughout gestation. Dietary interventions ceased at day of delivery. Offspring were culled at day 21 (D21) (weaning) and at 4 months (4 M) (young adult). Fetal exposure to excess maternal fructose intake significantly increased male and female triglycerides at D21 and 4 M and circulating palmitoleic acid and total omega-7 through day 0 (D0) to 4 M. Proteomic and functional analysis of significantly differentially expressed proteins revealed that FD offspring (D21 and 4 M) had significantly increased mitochondrial metabolic activities of ß-oxidation, electron transport chain (ETC) and oxidative phosphorylation and reactive oxygen species production compared to the CD offspring. Western blotting analysis of both FD offspring validated the increased protein abundances of mitochondrial ETC complex II and IV, SREBP-1c and FAS, whereas VDAC1 expression was higher at D21 but lower at 4 M. We provide evidence demonstrating offspring programmed hepatic mitochondrial metabolism and de novo lipogenesis following excess maternal fructose exposure. These underlying asymptomatic programmed pathways may lead to a predisposition to metabolic dysfunction later in life.
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Fructosa/efectos adversos , Metabolismo de los Lípidos/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Proteómica/métodos , Animales , Cromatografía Liquida , Proteínas del Complejo de Cadena de Transporte de Electrón/metabolismo , Ácidos Grasos Monoinsaturados/sangre , Femenino , Cobayas , Humanos , Masculino , Mitocondrias Hepáticas/efectos de los fármacos , Fosforilación Oxidativa/efectos de los fármacos , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , Especies Reactivas de Oxígeno/metabolismo , Espectrometría de Masas en Tándem , Triglicéridos/metabolismo , DesteteRESUMEN
BACKGROUND AND PURPOSE: Telestroke has been demonstrated to be a cost-effective means to expand access to care and improve outcomes in stroke; however, information on patient perceptions of this system of care delivery are limited. This study seeks to examine patient feedback of a national telestroke system within the Veterans Health Administration. METHODS: Patients who received a telestroke consultation were eligible for a phone interview 2 weeks later, including questions about technology quality, telepresence, and telestroke provider communication. Satisfaction scores ranged from 1 to 7 (higher=more satisfied) and for analyses were dichotomized as 6 to 7 indicating high satisfaction versus <6. Patient variables including stroke severity (measured by the National Institutes of Health Stroke Scale) were obtained from study records. Generalized estimating equation models were used to determine what factors were associated with patient satisfaction. RESULTS: Over 18 months, 186 interviews were completed, and 142 (76%) reported high satisfaction with telestroke. Patients with more severe stroke were less likely to recall the consultation. Factors significantly associated with patient satisfaction were higher ratings of the technology (P<0.0001), telepresence (P<0.0001), provider communication ratings (P<0.0001), and overall Veterans Affairs satisfaction (P=0.02). In the multivariate model, telepresence (odds ratio, 3.10 [95% CI, 1.81-5.31]) and provider ratings (odds ratio, 2.37 [95% CI, 1.20-4.68]) were independently associated with satisfaction. Veterans who were satisfied were more likely to recommend the technology (P<0.0001). CONCLUSIONS: Provider qualities, including telepresence and provider ratings, were associated with overall Veteran satisfaction with the telestroke consultation. Technology quality may be necessary but not sufficient to impact patient experience. Training providers to improve telepresence could improve patient experience with telestroke consultation.
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Satisfacción del Paciente , Rehabilitación de Accidente Cerebrovascular/métodos , Telemedicina/métodos , Anciano , Anciano de 80 o más Años , Comunicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atención Dirigida al Paciente , Derivación y Consulta , Estados Unidos , United States Department of Veterans Affairs , VeteranosRESUMEN
A recent Molecular Ecology editorial made a proactive statement of support for the "Nagoya Protocol" and the principle of benefit-sharing by requiring authors to provide a "Data Accessibility and Benefit-Sharing Statement" in their articles. Here, we encourage another step that enables Indigenous communities to provide their own definitions and aspirations for access and benefit-sharing alongside the author's "Statement". We invite the Molecular Ecology research community to use Biocultural-, Traditional Knowledge-, and Cultural Institution Notices to help Indigenous communities gain visibility within our research structures. Notices are one of the tools offered by the Biocultural Labels Initiative (part of the Local Contexts system) designed specifically for researchers and institutions. The Notices are highly visible, machine-readable icons that signal the Indigenous provenance of genetic resources, and rights of Indigenous communities to define the future use of genetic resources and derived benefits. The Notices invite collaboration with Indigenous communities and create spaces within our research systems for them to define the provenance, protocols, and permissions associated with genetic resources using Labels. Authors contributing to Molecular Ecology can apply Notices to their articles by providing the persistent unique identifier and an optional use-statement associated with the Notice in their "Data Accessibility and Benefit-Sharing Statement". In this way, our research community has an opportunity to accelerate support for the principles of the Nagoya Protocol, to alleviate concerns regarding Indigenous Data Sovereignty and equitable outcomes, and to build better relationships with Indigenous collaborators to enhance research, biodiversity, and conservation outcomes.
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BiodiversidadRESUMEN
We investigated the correlations and agreement between cognitive assessments made using a computerised (CogState™, six domains) and a standard pen-and-paper battery (five domains) in PWH and lifestyle-similar HIV-negative individuals. Demographically adjusted domain and global T-scores were obtained and used to define cognitive impairment according to the multivariate normative comparison (MNC) criteria. Correlations between T-scores and the agreement between the classifications of cognitive impairment obtained from the two batteries were assessed using the Spearman's rank correlation and Cohen's κ, respectively. The correlation between global T-scores from the two batteries was 0.52 (95% CI 0.44-0.60) in PWH and 0.45 (0.29-0.59) in controls (p = 0.38 for their difference). Correlations were generally stronger between domains within the same battery than between those from different batteries. The agreement between the two batteries in classifying individuals as cognitively impaired or not impaired was fair in PWH (κ = 0.24) and poor in HIV-negative individuals (κ = -0.02). The moderate correlation between overall cognitive function and the modest agreement between binary classifications of cognitive impairment obtained from two different batteries indicate the two batteries may assess slightly different components of cognition.
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Trastornos del Conocimiento , Disfunción Cognitiva , Infecciones por VIH , Cognición , Trastornos del Conocimiento/diagnóstico , Disfunción Cognitiva/diagnóstico , Infecciones por VIH/complicaciones , Humanos , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Research on HIV and reproduction has focused largely on women and heterosexual men. This article examines whether it is relevant to address parenthood in HIV care with gay men and what ways of doing so are most appropriate. METHODS: Qualitative interviews were conducted at four London clinics with 25 men living with HIV, aged 20-45, who did not have children, and 16 HIV clinicians. A thematic analysis identified potential reasons why parenthood was rarely discussed with gay men in HIV care. RESULTS: Two sets of ideas contributed to a lack of conversations about parenthood: clinicians' ideas about what matters to gay men and men's ideas about what it means to be HIV-positive. Both sets of ideas largely excluded having children, with patients and practitioners similarly unlikely to raise the topic of parenthood in the clinic. Contrary to what clinician commonly assumed, many men expressed interest in receiving more information, highlighting the importance of reassuring people upon diagnosis that it is possible to become parents while living with HIV. CONCLUSIONS: Parenting desires and intentions were rarely discussed with men in HIV care. Our findings illuminate the potentially beneficial effects of emphasising that having children is a possibility at diagnosis, regardless of patients' gender or sexuality. Conveying this information seems meaningful, not only to men who want to become parents in the future but also to others, as it appears to alleviate fears about mortality and ill health.