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Although immune check-point inhibitors (CPIs) revolutionized treatment of Merkel cell carcinoma (MCC), patients with CPI-refractory MCC lack effective therapy. More than 80% of MCC express T-antigens encoded by Merkel cell polyomavirus, which is an ideal target for T-cell receptor (TCR)-based immunotherapy. However, MCC often repress HLA expression, requiring additional strategies to reverse the downregulation for allowing T cells to recognize their targets. We identified TCRMCC1 that recognizes a T-antigen epitope restricted to human leukocyte antigen (HLA)-A*02:01. Seven CPI-refractory metastatic MCC patients received CD4 and CD8 T cells transduced with TCRMCC1 (TTCR-MCC1) preceded either by lymphodepleting chemotherapy or an HLA-upregulating regimen (single-fraction radiation therapy (SFRT) or systemic interferon gamma (IFNγ)) with concurrent avelumab. Two patients who received preceding SFRT and IFNγ respectively experienced tumor regression. One experienced regression of 13/14 subcutaneous lesions with 1 'escape' lesion and the other had delayed tumor regression in all lesions after initial progression. Although TTCR-MCC1 cells with an activated phenotype infiltrated tumors including the 'escape' lesion, all progressing lesions transcriptionally lacked HLA expression. While SFRT/IFNγ did not immediately upregulate tumor HLA expression, a secondary endogenous antigen-specific T cell infiltrate was detected in one of the regressing tumors and associated with HLA upregulation, indicating in situ immune responses have the potential to reverse HLA downregulation. Indeed, supplying a strong co-stimulatory signal via a CD200R-CD28 switch receptor allows TTCR-MCC1 cells to control HLA-downregulated MCC cells in a xenograft mouse model, upregulating HLA expression. Our results demonstrate the potential of TCR gene therapy for metastatic MCC and propose a next strategy for overcoming epigenetic downregulation of HLA in MCC.
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Background: MUC1 and UMOD pathogenic variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD). MUC1 is expressed in kidney, nasal mucosa and respiratory tract, while UMOD is expressed only in kidney. Due to haplo-insufficiency ADTKD- MUC1 patients produce approximately 50% of normal mucin-1. Methods: To determine whether decreased mucin-1 production was associated with an increased COVID-19 risk, we sent a survey to members of an ADTKD registry in September 2021, after the initial, severe wave of COVID-19. We linked results to previously obtained ADTKD genotype and plasma CA15-3 (mucin-1) levels and created a longitudinal registry of COVID-19 related deaths. Results: Surveys were emailed to 637 individuals, with responses from 89 ADTKD- MUC1 and 132 ADTKD- UMOD individuals. 19/83 (23%) ADTKD- MUC1 survey respondents reported a prior COVID-19 infection vs. 14/125 (11%) ADTKD- UMOD respondents (odds ratio (OR) 2.35 (95%CI 1.60-3.11, P = 0.0260). Including additional familial cases reported from survey respondents, 10/41 (24%) ADTKD- MUC1 individuals died of COVID-19 vs. 1/30 (3%) with ADTKD- UMOD , with OR 9.21 (95%CI 1.22-69.32), P = 0.03. The mean plasma mucin-1 level prior to infection in 14 infected and 27 uninfected ADTKD- MUC1 individuals was 7.06±4.12 vs. 10.21±4.02 U/mL ( P = 0.035). Over three years duration, our longitudinal registry identified 19 COVID-19 deaths in 360 ADTKD- MUC1 individuals (5%) vs. 3 deaths in 478 ADTKD- UMOD individuals (0.6%) ( P = 0.0007). Multivariate logistic regression revealed the following odds ratios (95% confidence interval) for COVID-19 deaths: ADTKD- MUC1 8.4 (2.9-29.5), kidney transplant 5.5 (1.6-9.1), body mass index (kg/m 2 ) 1.1 (1.0-1.2), age (y) 1.04 (1.0-1.1). Conclusions: Individuals with ADTKD- MUC1 are at an eight-fold increased risk of COVID-19 mortality vs. ADTKD- UMOD individuals. Haplo-insufficient production of mucin-1 may be responsible.
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Hypervariable region sequencing of the 16S ribosomal RNA (rRNA) gene plays a critical role in microbial ecology by offering insights into bacterial communities within specific niches. While providing valuable genus-level information, its reliance on data from targeted genetic regions limits its overall utility. Recent advances in sequencing technologies have enabled characterisation of the full-length 16S rRNA gene, enhancing species-level classification. Although current short-read platforms are cost-effective and precise, they lack full-length 16S rRNA amplicon sequencing capability. This study aimed to evaluate the feasibility of a modified 150 bp paired-end full-length 16S rRNA amplicon short-read sequencing technique on the Illumina iSeq 100 and 16S rRNA amplicon assembly workflow by utilising a standard mock microbial community and subsequently performing exploratory characterisation of captive (zoo) and free-ranging African elephant (Loxodonta africana) respiratory microbiota. Our findings demonstrate that, despite generating assembled amplicons averaging 869 bp in length, this sequencing technique provides taxonomic assignments consistent with the theoretical composition of the mock community and respiratory microbiota of other mammals. Tentative bacterial signatures, potentially representing distinct respiratory tract compartments (trunk and lower respiratory tract) were visually identified, necessitating further investigation to gain deeper insights into their implication for elephant physiology and health.
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Bacterias , Elefantes , Microbiota , ARN Ribosómico 16S , Animales , Elefantes/microbiología , Elefantes/genética , ARN Ribosómico 16S/genética , Bacterias/genética , Bacterias/clasificación , Microbiota/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Sistema Respiratorio/microbiología , Animales de Zoológico/microbiología , Análisis de Secuencia de ADN/métodos , Animales Salvajes/microbiología , FilogeniaRESUMEN
This scoping review aims to summarize current research on help-seeking behaviors and patterns among children who have experienced commercial sexual exploitation of children (CSEC) victimization and/or are at high risk of exploitation. Because the literature on help-seeking specific to CSEC victimization is limited, the current review was expanded to summarize findings from help-seeking research for children who have experienced harms that often co-occur with CSEC, such as maltreatment and homelessness. The authors searched three large article databases (PsycInfo, Ovid MEDLINE, and Web of Science) for articles that were (a) empirical; (b) measured or used the term "help-seeking" in their framing and/or results; (c) included children between the ages of 12 and 18; (d) primarily focused on children from the United States; (e) published in English. Ultimately, 22 articles met all inclusion criteria and were included in the final review. Results suggest that cisgender white females are the most likely to seek help, followed by sexual and gender minority children. Cisgender male children were the least likely to engage in help-seeking behaviors. Universally, children were more likely to engage in informal help-seeking rather than formal help-seeking, with younger children being more likely to reach out to parents and older children more likely to reach out to friends. Importantly, ethnically diverse children were under-represented, leading to limited information about how and why these children seek help. Implications for help-seeking by children impacted by commercial sexual exploitation are discussed, providing guidance for programming and research related to CSEC prevention.
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Directing energy flow in light harvesting assemblies of nanocrystal-chromophore hybrid systems requires a better understanding of factors that dictate excited-state processes. In this study, we explore excited-state interactions within the CsPbI3-cyanine dye (IR125) hybrid assembly through a comprehensive set of steady-state and time-resolved absorption and photoluminescence (PL) experiments. Our photoluminescence investigations reveal the quenching of CsPbI3 emission alongside the simultaneous enhancement of IR125 fluorescence, providing evidence for a singlet energy transfer. The evaluation of both photoluminescence (PL) quenching and PL decay measurements yield â¼94% energy transfer efficiency for the CsPbI3-IR125 hybrid assembly. Transient absorption spectroscopy further unveils that this singlet energy transfer process operates on an ultrafast time scale, occurring within 400 ps with a rate constant of energy transfer of 1.4 × 1010 s-1. Our findings highlight the potential of the CsPbI3-IR125 hybrid assembly to extend the emission of halide perovskites into the infrared region, paving the way for light energy harvesting and display applications.
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Sporadic cases of apolipoprotein A-IV medullary amyloidosis have been reported. Here we describe five families found to have autosomal dominant medullary amyloidosis due to two different pathogenic APOA4 variants. A large family with autosomal dominant chronic kidney disease (CKD) and bland urinary sediment underwent whole genome sequencing with identification of a chr11:116692578 G>C (hg19) variant encoding the missense mutation p.L66V of the ApoA4 protein. We identified two other distantly related families from our registry with the same variant and two other distantly related families with a chr11:116693454 C>T (hg19) variant encoding the missense mutation p.D33N. Both mutations are unique to affected families, evolutionarily conserved and predicted to expand the amyloidogenic hotspot in the ApoA4 structure. Clinically affected individuals suffered from CKD with a bland urinary sediment and a mean age for kidney failure of 64.5 years. Genotyping identified 48 genetically affected individuals; 44 individuals had an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73 m2, including all 25 individuals with kidney failure. Significantly, 11 of 14 genetically unaffected individuals had an eGFR over 60 ml/min/1.73 m2. Fifteen genetically affected individuals presented with higher plasma ApoA4 concentrations. Kidney pathologic specimens from four individuals revealed amyloid deposits limited to the medulla, with the mutated ApoA4 identified by mass-spectrometry as the predominant amyloid constituent in all three available biopsies. Thus, ApoA4 mutations can cause autosomal dominant medullary amyloidosis, with marked amyloid deposition limited to the kidney medulla and presenting with autosomal dominant CKD with a bland urinary sediment. Diagnosis relies on a careful family history, APOA4 sequencing and pathologic studies.
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Amiloidosis , Apolipoproteínas A , Nefritis Intersticial , Insuficiencia Renal Crónica , Humanos , Persona de Mediana Edad , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/genética , Nefritis Intersticial/complicaciones , Mutación , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/complicacionesRESUMEN
Animal tuberculosis is a significant infectious disease affecting both livestock and wildlife populations worldwide. Effective disease surveillance and characterization of Mycobacterium bovis (M. bovis) strains are essential for understanding transmission dynamics and implementing control measures. Currently, sequencing of genomic information has relied on culture-based methods, which are time-consuming, resource-demanding, and concerning in terms of biosafety. This study explores the use of culture-independent long-read whole-genome sequencing (WGS) for a better understanding of M. bovis epidemiology in African buffaloes (Syncerus caffer). By comparing two sequencing approaches, we evaluated the efficacy of Illumina WGS performed on culture extracts and culture-independent Oxford Nanopore adaptive sampling (NAS). Our objective was to assess the potential of NAS to detect genomic variants without sample culture. In addition, culture-independent amplicon sequencing, targeting mycobacterial-specific housekeeping and full-length 16S rRNA genes, was applied to investigate the presence of microorganisms, including nontuberculous mycobacteria. The sequencing quality obtained from DNA extracted directly from tissues using NAS is comparable to the sequencing quality of reads generated from culture-derived DNA using both NAS and Illumina technologies. We present a new approach that provides complete and accurate genome sequence reconstruction, culture independently, and using an economically affordable technique.
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Regular attendance is integral for students' academic success; it also affects adolescents' physical and mental health. Very few studies consider (a) differences between partial- and full-day absences regarding chronic absenteeism (CA; missing school ≥15 days in an academic year); or (b) roles of school nurses in addressing student absenteeism. This study describes school nurses' perceptions of factors related to CA and differences between partial- and full-day absences by analyzing qualitative data from six focus groups with 21 Midwestern school nurses. Four themes emerged: Absenteeism at the intersection of family and health; Absenteeism at the intersection of family and school; Absenteeism at the intersection of family and ecological systems; and School nurse roles in supporting chronically absent students. Findings highlight the importance of school nurses by describing their role in identifying students who are at risk for CA, allowing for effective assessment and intervention with students before patterns of CA become habitual.
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Human trafficking is a serious crime and violation of human rights that results in numerous harms. Although the phenomenon is not new, scholarship on the issue has grown substantially since the first legal framework was passed in 2000. However, the existing literature has been criticized for its skewed focus on victims, among other things. The dearth of information on traffickers and their operations limits our ability to reduce or prevent perpetration. The current study presents a comprehensive and critical review of the existing literature focused on traffickers to synthesize what is already known and highlight the key gaps. Twenty-nine articles met the inclusion criteria of (1) focusing on traffickers and their operations and (2) relying on data either directly from traffickers or sources that contained detailed information about criminal cases against traffickers. We used an iterative process to identify relevant studies, which included collecting articles of which we were already familiar or were identified in existing reviews, searching their reference lists, and conducting cited-by searches until saturation was reached. Topics found in the extant literature included: characteristics of traffickers, relationships between traffickers and victims, organizational characteristics and networks, operations, connections with other crimes, motivations, perceptions of behavior, and risks associated with trafficking. It concludes with recommendations for future research and a discussion of how bridging gaps in the literature could support more rigorous mathematical modeling that is needed to identify and assess promising perpetration prevention and intervention strategies.
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Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an increasingly recognized cause of chronic kidney disease. ADTKD pregnancy outcomes have not previously been described. Methods: A cross-sectional survey was sent to women from ADTKD families. Results: Information was obtained from 85 afffected women (164 term pregnancies) and 23 controls (50 pregnancies). Only 16.5% of genetically affected women knew they had ADTKD during pregnancy. Eighteen percent of ADTKD mothers had hypertension during pregnancy versus 12% in controls (p = 0.54) and >40% in comparative studies of chronic kidney disease in pregnancy. Eleven percent of births of ADTKD mothers were <37 weeks versus 0 in controls (p < 0.0001). Cesarean section occurred in 19% of pregnancies in affected women versus 38% of unaffected individuals (p = 0.06). Only 12% of babies required a neonatal intensive care unit stay. Conclusions: ADTKD pregnancies had lower rates of hypertension during pregnancy versus other forms of chronic kidney disease, which may have contributed to good maternal and fetal outcomes.
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BACKGROUND: Clinical studies suggest that anaesthesia exposure early in life affects neurobehavioural development. We designed a non-human primate (NHP) study to evaluate cognitive, behavioural, and brain functional and structural alterations after isoflurane exposure during infancy. These NHPs displayed decreased close social behaviour and increased astrogliosis in specific brain regions, most notably in the amygdala. Here we hypothesise that resting-state functional connectivity MRI can detect alterations in connectivity of brain areas that relate to these social behaviours and astrogliosis. METHODS: Imaging was performed in 2-yr-old NHPs under light anaesthesia, after early-in-life (postnatal days 6-12) exposure to 5 h of isoflurane either one or three times, or to room air. Brain images were segmented into 82 regions of interest; the amygdala and the posterior cingulate cortex were chosen for a seed-based resting-state functional connectivity MRI analysis. RESULTS: We found differences between groups in resting-state functional connectivity of the amygdala and the auditory cortices, medial premotor cortex, and posterior cingulate cortex. There were also alterations in resting-state functional connectivity between the posterior cingulate cortex and secondary auditory, polar prefrontal, and temporal cortices, and the anterior insula. Relationships were identified between resting-state functional connectivity alterations and the decrease in close social behaviour and increased astrogliosis. CONCLUSIONS: Early-in-life anaesthesia exposure in NHPs is associated with resting-state functional connectivity alterations of the amygdala and the posterior cingulate cortex with other brain regions, evident at the juvenile age of 2 yr. These changes in resting-state functional connectivity correlate with the decrease in close social behaviour and increased astrogliosis. Using resting-state functional connectivity MRI to study the neuronal underpinnings of early-in-life anaesthesia-induced behavioural alterations could facilitate development of a biomarker for anaesthesia-induced developmental neurotoxicity.
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Isoflurano , Animales , Isoflurano/efectos adversos , Gliosis , Encéfalo/diagnóstico por imagen , Giro del Cíngulo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Primates , Mapeo Encefálico/métodos , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiologíaRESUMEN
Huntington disease (HD) is a neurodegenerative disorder caused by an expanded polyglutamine (CAG) trinucleotide expansion in the huntingtin (HTT) gene that encodes the mutant huntingtin protein (mHTT). Visualization and quantification of cerebral mHTT will provide a proxy for target engagement and a means to evaluate therapeutic interventions aimed at lowering mHTT in the brain. Here, we validated the novel radioligand 11C-labeled 6-(5-((5-methoxypyridin-2-yl)methoxy)benzo[d]oxazol-2-yl)-2-methylpyridazin-3(2H)-one (11C-CHDI-180R) using PET imaging to quantify cerebral mHTT aggregates in a macaque model of HD. Methods: Rhesus macaques received MRI-guided intrastriatal delivery of a mixture of AAV2 and AAV2.retro viral vectors expressing an HTT fragment bearing 85 CAG repeats (85Q, n = 5), a control HTT fragment bearing 10 CAG repeats (10Q, n = 4), or vector diluent only (phosphate-buffered saline, n = 5). Thirty months after surgery, 90-min dynamic PET/CT imaging was used to investigate 11C-CHDI-180R brain kinetics, along with serial blood sampling to measure input function and stability of the radioligand. The total volume of distribution was calculated using a 2-tissue-compartment model as well as Logan graphical analysis for regional quantification. Immunostaining for mHTT was performed to corroborate the in vivo findings. Results: 11C-CHDI-180R displayed good metabolic stability (51.4% ± 4.0% parent in plasma at 60 min after injection). Regional time-activity curves displayed rapid uptake and reversible binding, which were described by a 2-tissue-compartment model. Logan graphical analysis was associated with the 2-tissue-compartment model (r 2 = 0.96, P < 0.0001) and used to generate parametric volume of distribution maps. Compared with controls, animals administered the 85Q fragment exhibited significantly increased 11C-CHDI-180R binding in several cortical and subcortical brain regions (group effect, P < 0.0001). No difference in 11C-CHDI-180R binding was observed between buffer and 10Q animals. The presence of mHTT aggregates in the 85Q animals was confirmed histologically. Conclusion: We validated 11C-CHDI-180R as a radioligand to visualize and quantify mHTT aggregated species in a HD macaque model. These findings corroborate our previous work in rodent HD models and show that 11C-CHDI-180R is a promising tool to assess the mHTT aggregate load and the efficacy of therapeutic strategies.
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Enfermedad de Huntington , Animales , Enfermedad de Huntington/metabolismo , Proteína Huntingtina/genética , Tomografía Computarizada por Tomografía de Emisión de Positrones , Macaca mulatta/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Tomografía de Emisión de Positrones , Modelos Animales de EnfermedadRESUMEN
Allogeneic hematopoietic stem cell transplantation (alloHSCT) from donors lacking C-C chemokine receptor 5 (CCR5Δ32/Δ32) can cure HIV, yet mechanisms remain speculative. To define how alloHSCT mediates HIV cure, we performed MHC-matched alloHSCT in SIV+, anti-retroviral therapy (ART)-suppressed Mauritian cynomolgus macaques (MCMs) and demonstrated that allogeneic immunity was the major driver of reservoir clearance, occurring first in peripheral blood, then peripheral lymph nodes, and finally in mesenteric lymph nodes draining the gastrointestinal tract. While allogeneic immunity could extirpate the latent viral reservoir and did so in two alloHSCT-recipient MCMs that remained aviremic >2.5 years after stopping ART, in other cases, it was insufficient without protection of engrafting cells afforded by CCR5-deficiency, as CCR5-tropic virus spread to donor CD4+ T cells despite full ART suppression. These data demonstrate the individual contributions of allogeneic immunity and CCR5 deficiency to HIV cure and support defining targets of alloimmunity for curative strategies independent of HSCT.
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Infecciones por VIH , Trasplante de Células Madre Hematopoyéticas , Síndrome de Inmunodeficiencia Adquirida del Simio , Virus de la Inmunodeficiencia de los Simios , Animales , Macaca fascicularis , Carga ViralRESUMEN
Purpose: The objective of the current study was to describe outcomes on physiological and perceptual measures of auditory function in human listeners with and without a history of recreational firearm noise exposure related to hunting. Design: This study assessed the effects of hunting-related recreational firearm noise exposure on audiometric thresholds, oto-acoustic emissions (OAEs), brainstem neural representation of fundamental frequency (F0) in frequency following responses (FFRs), tonal middle-ear muscle reflex (MEMR) thresholds, and behavioral tests of auditory processing in 20 young adults with normal hearing sensitivity. Results: Performance on both physiological (FFR, MEMR) and perceptual (behavioral auditory processing tests) measures of auditory function were largely similar across participants, regardless of hunting-related recreational noise exposure. On both behavioral and neural measures including different listening conditions, performance degraded as difficulty of listening condition increased for both nonhunter and hunter participants. A right-ear advantage was observed in tests of dichotic listening for both nonhunter and hunter participants. Conclusion: The null results in the current study could reflect an absence of cochlear synaptopathy in the participating cohort, variability related to participant characteristics and/or test protocols, or an insensitivity of the selected physiological and behavioral auditory measures to noise-induced synaptopathy.
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Pérdida Auditiva Provocada por Ruido , Percepción del Habla , Humanos , Adulto Joven , Pérdida Auditiva Provocada por Ruido/etiología , Caza , Estimulación Acústica , Umbral Auditivo/fisiología , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , AudiciónRESUMEN
OBJECTIVES: Cisgender girls and boys report trading sex for something of value at roughly equal proportions; yet, boys are understudied and underserved. We compare boys who reported trading sex to those who never traded sex to address this gap in knowledge and practice. METHODS: The study is a secondary analysis of the Minnesota Student Survey, a triannual, census-style survey. The sample included 32 311 cisgender boy students in ninth and 11th grades who answered a question about sex trading. Bivariate descriptive statistics and multivariate logistic models were used to identify associated factors and determine the odds of trading sex on the basis of specific experiences. RESULTS: We found that 1.2% of boys reported trading sex. In bivariate analyses, boys who reported trading sex were more likely than those who did not to: identify as Black or Indigenous; report a marginalized gender identity or sexual expression; have had sexual intercourse; have experienced sexual harassment and harassment on the basis of sexual identity and race, ethnicity, and national origin; and to have experienced homelessness, food insecurity, foster care, and substance treatment (P < .001). In multivariate models, we found increased odds of trading sex for some variables, including a marginalized sexual identity, identifying as Black, and experiences of unstable housing, foster care, substance treatment, sexual harassment, and harassment based on gender (P < .001). CONCLUSIONS: These findings contribute new knowledge about boys who trade sex using a large, population-based sample and counter false assumptions and stereotypes. These data suggest new avenues of research, intervention, and prevention.
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Identidad de Género , Conducta Sexual , Humanos , Masculino , Adolescente , Femenino , Etnicidad , Encuestas y Cuestionarios , Modelos LogísticosRESUMEN
Polycystic ovary syndrome (PCOS) is associated with irregular menstrual cycles, hyperandrogenemia, and obesity. It is currently accepted that women with PCOS are also at risk for endometriosis, but the effect of androgen and obesity on endometriosis has been underexplored. The goal of this study was to determine how testosterone (T) and an obesogenic diet impact the progression of endometriosis in a nonhuman primate (NHP) model. Female rhesus macaques were treated with T (serum levels approximately 1.35 ng/ml), Western-style diet (WSD; 36% of calories from fat compared to 16% in standard monkey chow) or the combination (T + WSD) at the time of menarche as part of a longitudinal study for ~7 years. Severity of endometriosis was determined based on American Society for Reproductive Medicine (ASRM) revised criteria, and staged 1-4. Stages 1 and 2 were associated with extent of abdominal adhesions, while stages 3 and 4 were associated with presence of chocolate cysts. The combined treatment of T + WSD resulted in earlier onset of endometriosis and more severe types associated with large chocolate cysts compared to all other treatments. There was a strong correlation between glucose clearance, homeostatic model assessment for insulin resistance (HOMA-IR), and total percentage of body fat with presence of cysts, indicating possible indirect contribution of hyperandrogenemia via metabolic dysfunction. An RNA-seq analysis of omental adipose tissue revealed significant impacts on a number of inflammatory signaling pathways. The interactions between obesity, hyperandrogenemia, and abdominal inflammation deserve additional investigation in NHP model species.
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Dieta Occidental , Endometriosis , Resistencia a la Insulina , Síndrome del Ovario Poliquístico , Testosterona , Animales , Femenino , Humanos , Índice de Masa Corporal , Endometriosis/complicaciones , Estudios Longitudinales , Macaca mulatta , Obesidad/metabolismo , Síndrome del Ovario Poliquístico/metabolismo , Testosterona/farmacología , Dieta Occidental/efectos adversosRESUMEN
Falls are a serious public health problem, especially for older adults with chronic conditions. The purpose of this systematic review was to evaluate the translational potential of physical activity-based balance interventions for older adults with common chronic conditions guided by the Reach, Effectiveness/Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) framework. Databases were searched (2011-2021) to identify studies with physical activity-based fall prevention interventions for older adults with chronic conditions. Data were collected using the RE-AIM coding guide and Mixed Methods Appraisal Tool for evidence quality. The search yielded 122 articles, of which 14 distinct studies were included. The most reported RE-AIM dimensions across the studies were Reach (46.2%) and Implementation (40.5%), with Effectiveness/Efficacy (29.4%), Adoption (2.0%), and Maintenance (5.4%) being the least reported. Studies were largely conducted in controlled research environments with minimal staff involvement and without long-term follow-up periods. While studies found that physical activity-based programs were effective in improving balance, information on representativeness and adoption/maintenance of programs was lacking. Studies included sufficient details about the intervention (content, dosage, progression). External validity RE-AIM indicators were reported less frequently than internal validity indicators. The studies were of moderate quality overall. Studies often lacked information on indicators critical for understanding how to implement these programs. This review signals the need to investigate the translation of these interventions from controlled research settings to clinical settings to improve the public impact of fall prevention for this population.
Falls are a serious public health problem, especially for older adults with chronic diseases who have a higher risk of falling. For this review paper, we gathered similar research articles that looked at the effects of balance exercise programs in older adults with a variety of chronic diseases and reviewed how likely they could be used in real-world settings using a guide. We found fourteen studies that met our criteria. The most common elements that authors included in their reports were how research subjects were identified and details about the exercise program design/delivery. The least common elements were the scientific outcomes of the program, how/where the program was incorporated, and the long-term effects of the program. While these balance exercise programs for older adults with chronic diseases were successful in these individual research studies, this general area of fall research is somewhat underdeveloped. Researchers should put more consideration into surroundings where these programs could take place and study how these programs could be successful in real-world settings long-term.
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Accidentes por Caídas , Ejercicio Físico , Humanos , Anciano , Accidentes por Caídas/prevención & control , Actividad Motora , Conductas Relacionadas con la Salud , Enfermedad CrónicaRESUMEN
OBJECTIVE: Describe Greek life students' perspectives of party culture, safety, and College Sexual Violence (CSV) prevention. PARTICIPANTS: 27 US undergraduates: 5 fraternity underclassmen, 6 fraternity upperclassmen, 10 sorority underclassmen, 6 sorority upperclassmen. METHODS: Students participated in one of four focus groups, separately by gender and academic year. Facilitation guide addressed partying, sexual violence, and safety. RESULTS: Greek life members described partying preferences, perceived safety threats, and actions they took to party safely. University efforts to support safe partying were not universally viewed as helpful. CONCLUSIONS: Although Greek life students strive to create safe partying environments, there remain missed opportunities to mitigate risks related to CSV. The responsibility to ensure safe partying falls too heavily on students, resulting in universities missing opportunities to provide measures that promote safety while mitigating risks and potentially serious harms.