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Similar to the human brain, Drosophila glia may well be divided into several subtypes that each carries out specific functions. Glial GPCRs play key roles in crosstalk between neurons and glia. Drosophila Lgr4 (dLgr4) is a human relaxin receptor homolog involved in angiogenesis, cardiovascular regulation, collagen remodeling, and wound healing. A recent study suggests that ilp7 might be the ligand for Lgr4 and regulates escape behavior of Drosophila larvae. Here we demonstrate that Drosophila Lgr4 expression in glial cells, not neurons, is necessary for early development, adult behavior, and lifespan. Reducing the Lgr4 level in glial cells disrupts Drosophila development, while knocking down other LGR family members in glia has no impact. Adult-specific knockdown of Lgr4 in glia but not neurons reduce locomotion, male reproductive success, and animal longevity. The investigation of how glial expression of Lgr4 contributes to this behavioral alteration will increase our understanding of how insulin signaling via glia selectively modulates neuronal activity and behavior.
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Proteínas de Drosophila , Drosophila , Neuroglia , Receptores Acoplados a Proteínas G , Animais , Masculino , Encéfalo , Neurônios , Receptores de Neuropeptídeos , Receptores Acoplados a Proteínas G/genética , Proteínas de Drosophila/genéticaRESUMO
BACKGROUND: Achieving clinically significant weight loss through lifestyle interventions for obesity management is challenging for most individuals. Improving intervention effectiveness involves early identification of intervention nonresponders and providing them with timely, tailored interventions. Early and frequent self-monitoring (SM) adherence predicts later weight loss success, making it a potential indicator for identifying nonresponders in the initial phase. OBJECTIVE: This study aims to identify clinically meaningful participant subgroups based on longitudinal adherence to SM of diet, activity, and weight over 6 months as well as psychological predictors of participant subgroups from a self-determination theory (SDT) perspective. METHODS: This was a secondary data analysis of a 6-month digital lifestyle intervention for adults with overweight or obesity. The participants were instructed to perform daily SM on 3 targets: diet, activity, and weight. Data from 50 participants (mean age: 53.0, SD 12.6 y) were analyzed. Group-based multitrajectory modeling was performed to identify subgroups with distinct trajectories of SM adherence across the 3 SM targets. Differences between subgroups were examined for changes in clinical outcomes (ie, body weight, hemoglobin A1c) and SDT constructs (ie, eating-related autonomous motivation and perceived competence for diet) over 6 months using linear mixed models. RESULTS: Two distinct SM trajectory subgroups emerged: the Lower SM group (21/50, 42%), characterized by all-around low and rapidly declining SM, and the Higher SM group (29/50, 58%), characterized by moderate and declining diet and weight SM with high activity SM. Since week 2, participants in the Lower SM group exhibited significantly lower levels of diet (P=.003), activity (P=.002), and weight SM (P=.02) compared with the Higher SM group. In terms of clinical outcomes, the Higher SM group achieved a significant reduction in body weight (estimate: -6.06, SD 0.87 kg; P<.001) and hemoglobin A1c (estimate: -0.38, SD 0.11%; P=.02), whereas the Lower SM group exhibited no improvements. For SDT constructs, both groups maintained high levels of autonomous motivation for over 6 months. However, the Lower SM group experienced a significant decline in perceived competence (P=.005) compared with the Higher SM group, which maintained a high level of perceived competence throughout the intervention (P=.09). CONCLUSIONS: The presence of the Lower SM group highlights the value of using longitudinal SM adherence trajectories as an intervention response indicator. Future adaptive trials should identify nonresponders within the initial 2 weeks based on their SM adherence and integrate intervention strategies to enhance perceived competence in diet to benefit nonresponders. TRIAL REGISTRATION: ClinicalTrials.gov NCT05071287; https://clinicaltrials.gov/study/NCT05071287. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1016/j.cct.2022.106845.
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Estilo de Vida , Obesidade , Sobrepeso , Adulto , Humanos , Pessoa de Meia-Idade , Hemoglobinas Glicadas , Obesidade/terapia , Sobrepeso/terapia , Redução de Peso , IdosoRESUMO
Introduction: Addressing femoral neck fractures resulting from ground-level falls in older adults with Alzheimer's disease (AD) involves a personalized treatment plan. There is considerable ongoing debate concerning the relative advantages and disadvantages of surgical treatment (internal fixation or arthroplasty) vs nonoperative treatment for femoral neck fractures in older persons with AD. Methods: This retrospective cohort study compared the mortality, hazard ratio, and survival rate between operative and nonoperative treatments, controlling for patients' demographic information and baseline health status. The study population consisted of Optum beneficiaries diagnosed with AD who experienced an initial femoral neck fracture claim between January 1, 2012, and December 31, 2017. Kaplan-Meier survival curves were applied to compare the treatment groups' post-fracture survival rates and mortality. Cox regression was used to examine the survival period by controlling the covariates. Results: Out of the 4157 patients with AD with femoral neck fractures, 59.8% were women (n = 2487). The median age was 81 years. The 1-year survival rate for nonoperative treatment (70.19%) was lower than that for internal fixation (75.27%) and arthroplasty treatment (82.32%). Compared with the nonoperative group, arthroplasty surgical treatment had significant lower hazard risk of death (arthroplasty hazard ratio: 0.850, 95% CI: 0.728-0.991, P < 0.05). Discussion: The findings suggest that the operative treatment group experiences higher survival rates and lower mortality rates than the nonoperative group. This paper provides insights into treatment outcomes of older adults with AD receiving medical care for femoral neck fractures.
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Importance: The Hospital-Acquired Condition Reduction Program (HACRP) evaluates acute care hospitals on the occurrence of patient safety events and health care-associated infections. Since its implementation, several studies have raised concerns about the overpenalization of teaching and safety-net hospitals, and although several changes in the program's methodology have been applied in the last few years, whether these changes reversed the overpenalization of teaching and safety-net hospitals is unknown. Objective: To determine hospital characteristics associated with HACRP penalization and penalization reversal. Design, Setting, and Participants: This retrospective cross-sectional study assessed data from 3117 acute care hospitals participating in the HACRP. The HACRP penalization and hospital characteristics were obtained from Hospital Compare (2020 and 2021), the Inpatient Prospective Payment System impact file (2020), and the American Hospital Association annual survey (2018). Exposures: Hospital characteristics, including safety-net status and teaching intensity (no teaching and very minor, minor, major, and very major teaching levels). Main Outcomes and Measures: The primary outcome was HACRP penalization (ie, hospitals that fell within the worst quartile of the program's performance). Multivariable models initially included all covariates, and then backward stepwise variable selection was used. Results: Of 3117 hospitals that participated in HACRP in 2020, 779 (25.0%) were safety-net hospitals and 1090 (35.0%) were teaching institutions. In total, 771 hospitals (24.7%) were penalized. The HACRP penalization was associated with safety-net status (odds ratio [OR], 1.41 [95% CI, 1.16-1.71]) and very major teaching intensity (OR, 1.94 [95% CI, 1.15-3.28]). In addition, non-federal government hospitals were more likely to be penalized than for-profit hospitals (OR, 1.62 [95% CI, 1.23-2.14]), as were level I trauma centers (OR, 2.05 [95% CI, 1.43-2.96]) and hospitals located in the New England region (OR, 1.65 [95% CI, 1.12-2.43]). Safety-net hospitals with major teaching levels were twice as likely to be penalized as non-safety-net nonteaching hospitals (OR, 2.15 [95% CI, 1.14-4.03]). Furthermore, safety-net hospitals penalized in 2020 were less likely (OR, 0.64 [95% CI, 0.43-0.96]) to revert their HACRP penalization status in 2021. Conclusions and Relevance: Findings from this cross-sectional study indicated that teaching and safety-net hospital status continued to be associated with overpenalization in the HACRP despite recent changes in its methodology. Most of these hospitals were also less likely to revert their penalization status. A reevaluation of the program methodology is needed to avoid depleting resources of hospitals caring for underserved populations.
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Doença Iatrogênica , Provedores de Redes de Segurança , Estados Unidos , Humanos , Estudos Retrospectivos , Estudos Transversais , HospitaisRESUMO
GOAL AND AIMS: To pilot the feasibility and evaluate the performance of an EEG wearable for measuring sleep in individuals with Parkinson's disease. FOCUS TECHNOLOGY: Dreem Headband, Version 2. REFERENCE TECHNOLOGY: Polysomnography. SAMPLE: Ten individuals with Parkinson's disease. DESIGN: Individuals wore Dreem Headband during a single night of polysomnography. CORE ANALYTICS: Comparison of summary metrics, bias, and epoch-by-epoch analysis. ADDITIONAL ANALYTICS AND EXPLORATORY ANALYSES: Correlation of summary metrics with demographic and Parkinson's disease characteristics. CORE OUTCOMES: Summary statistics showed Dreem Headband overestimated several sleep metrics, including total sleep, efficiency, deep sleep, and rapid eye movement sleep, with an exception in light sleep. Epoch-by-epoch analysis showed greater specificity than sensitivity, with adequate accuracy across sleep stages (0.55-0.82). IMPORTANT SUPPLEMENTAL OUTCOMES: Greater Parkinson's disease duration and rapid eye movement behavior were associated with more wakefulness, and worse Parkinson's disease motor symptoms were associated with less deep sleep. CORE CONCLUSION: The Dreem Headband performs similarly in Parkinson's disease as it did in non-Parkinson's disease samples and shows promise for improving access to sleep assessment in people with Parkinson's disease.
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Doença de Parkinson , Humanos , Polissonografia , Doença de Parkinson/complicações , Sono , Fases do Sono , EletroencefalografiaRESUMO
Context: Cardiovascular disease (CVD) in transgender women (TW) may be affected by gender-affirming hormone therapy (GAHT) and HIV, but few data compare TW on contemporary GAHT to well-matched controls. Objective: We compared CVD burden and biomarker profiles between TW and matched cisgender men (CM). Methods: Adult TW on GAHT (n = 29) were recruited for a cross-sectional study (2018-2020). CM (n = 48) from the former Multicenter AIDS Cohort Study were matched 2:1 to TW on HIV serostatus, age ±5 years, race/ethnicity, BMI category and antiretroviral therapy (ART) type. Cardiac parameters were measured by CT and coronary atherosclerosis by coronary CT angiography; sex hormone and biomarker concentrations were measured centrally from stored samples. Results: Overall, median age was 53 years and BMI 29 kg/m2; 69% were non-white. All participants with HIV (71%) had viral suppression on ART. Only 31% of TW had testosterone suppression (<50 ng/dL, TW-S). Traditional CVD risk factors were similar between groups, except that TW-S had higher BMI than TW with non-suppressed testosterone (TW-T). TW-S had no evidence of non-calcified coronary plaque or advanced coronary stenosis, whereas TW-T and CM had similar burden. TW had lower prevalence of any coronary plaque, calcified plaque and mixed plaque than CM, regardless of testosterone concentrations and HIV serostatus. Estradiol but not testosterone concentrations moderately and negatively correlated with the presence of coronary plaque and stenosis. Small sample size limited statistical power. Conclusion: Older TW with suppressed total testosterone on GAHT had no CT evidence of non-calcified coronary plaque or advanced coronary stenosis. Longitudinal studies to understand relationships between GAHT and CVD risk in TW are needed.