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BACKGROUND: Mental health outcomes can be influenced by various factors, one of which has recently gained attention, namely food security. Food security is paramount to maintaining not only physical, but also mental health. There is an increasing need to understand the interplay between food insecurity (FI) and mental health outcomes, especially among vulnerable populations. The objective of this study was to investigate the effect of FI on psychological health (anxiety and depression) as well as to examine the modifying effect of socioeconomic position on this relationship. METHODS: A cross-sectional study was conducted in Maputo City, Mozambique, in 1,842 participants. Data were collected through structured interviews using a modified version of the US Department of Agriculture Household Food Security Module to measure FI, and the Hospital Anxiety and Depression Scale to measure anxiety and depression. A composite variable for psychological health was created. Propensity score matching and interaction effect analyses were employed to examine the effects of FI on psychological health and the moderating role of socioeconomic position. RESULTS: Of the 1,174 participants randomly assigned to propensity score matching, 787 were exposed to FI while 387 were unexposed. The analysis revealed stark disparities in psychological health outcomes associated with FI. The risk of poor psychological health among those exposed to FI was 25.79%, which was significantly higher than the 0.26% in unexposed individuals. The risk difference was 25.54% points (95% CI: 22.44-28.63), with a risk ratio of 99.82. Our assessment of population attributable fractions indicated that nearly all the risk for poor psychological health in the exposed group could be ascribed to FI. The interaction effects analysis revealed that socioeconomic status modifies this relationship. Specifically, heads of food-insecure households with a lower socioeconomic position tended to report poor mental health compared to their food-secure counterparts with a higher position. CONCLUSIONS: The findings underscore the profound impact of FI on the mental health of household heads in Maputo City, socioeconomic position being a significant modifier. Addressing household FI along with the socioeconomic position of household heads could be pivotal to mental health promotion, especially among vulnerable populations.
Assuntos
Depressão , Insegurança Alimentar , Pontuação de Propensão , Humanos , Masculino , Estudos Transversais , Feminino , Adulto , Depressão/epidemiologia , Depressão/psicologia , Pessoa de Meia-Idade , Moçambique/epidemiologia , Saúde Mental/estatística & dados numéricos , Ansiedade/epidemiologia , Ansiedade/psicologia , Classe Social , Adulto Jovem , Características da Família , Fatores SocioeconômicosRESUMO
The use of chiral medicines (possessing center(s) of asymmetric carbon) may cause adverse drug reactions (ADRs). The safety assurance of these medicines is critical. We aimed to evaluate registered and commonly used anti-infective chiral medicines circulating in the Tanzanian market to establish their safety profile to protect public health. A mixed prospective-retrospective cohort study was conducted to assess the safety profile of amoxicillin, amoxicillin-clavulanic acid and ceftriaxone injection. ADRs causality assessment was conducted by using World Health Organization (WHO)-Algorithm criteria. Data were collected from 7 tertiary hospitals: Muhimbili National Hospital (MNH), Kilimanjaro Christian Medical Centre (KCMC), Bugando Medical Centre (BMC), Ligula Referral-Regional Hospital (LRRH), Kitete Referral-Regional Hospital (KRRH), Dodoma Referral-Regional Hospital (DRRH), and Mbeya Zonal-Referral Hospital (MZRH). Data were supplemented by those recorded in the WHO-Vigiflow/VigiLyze database within the same monitoring period. Data were analyzed using STATA version-15. The results were considered statistically significant when P < .05. A total of 2522 patients were enrolled in hospitals: MNH (499), KCMC (407), BMC (396), LRRH (387), KRRH (345), DRRH (249), and MZRH (239). Among those, 1197 (47.5%) were treated with ceftriaxone, 585 (23.2%) amoxicillin and 740(29.3%) amoxicillin-clavulanic acid. Out of those, 102 (4.5%) experienced adverse events (AEs), 49 (48%) were due to ceftriaxone, 37 (36.3%) amoxicillin-clavulanic acid and 16 (15.7%) amoxicillin (P-value .012). A total of 443 participants from the enrolled and WHO-Vigiflow/VigiLyze database were experienced with ADRs. The ADRs affected mainly gastro-intestinal system 234 (53%), skin and subcutaneous tissue 85 (19%), nervous system 49 (11%), respiratory thoracic 22 (5%), and general disorders 18(4%). In this study, approximately 90% of reported AEs were ADRs possible-related to the monitored medicines, with few plausible and certain. Ceftriaxone injection caused more ADRs. Amoxicillin-clavulanic acid was associated with more ADRs than amoxicillin alone. The safety profile of these medicines is still maintained; however, comprehensive monitoring of ADRs is recommended to improve patient safety and enhance overall treatment outcomes.
Assuntos
Combinação Amoxicilina e Clavulanato de Potássio , Amoxicilina , Antibacterianos , Ceftriaxona , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Ceftriaxona/efeitos adversos , Feminino , Masculino , Estudos Prospectivos , Adulto , Pessoa de Meia-Idade , Antibacterianos/efeitos adversos , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Amoxicilina/efeitos adversos , Adolescente , Estudos Retrospectivos , Criança , Idoso , Pré-EscolarRESUMO
Importance: Prohibiting the sale of commonly preferred e-cigarette flavors (eg, fruity and sweet) to discourage use among youths poses a risk of diminishing efforts to decrease smoking in adults. Objective: To compare reductions in smoking achieved in adults with psychiatric conditions or lower educational level using very low nicotine content (VLNC) cigarettes alone, combined with e-cigarettes limited to tobacco flavor (TF), or combined with e-cigarettes in participant-preferred flavors. Design, Setting, and Participants: Three randomized clinical trials were conducted for 16 weeks from October 2020 through November 2023 at the University of Vermont, Brown University, and Johns Hopkins University. Participants were adults who smoked daily and were not planning to quit in the next 30 days. These participants were from 3 at-risk populations: those with affective disorders, exemplifying mental illness; those with opioid use disorder, exemplifying substance use disorders; and females of reproductive age with a high-school education or less, exemplifying lower educational level. Participants were randomly assigned to 1 of 4 experimental conditions: (1) normal nicotine content (NNC) cigarettes only; (2) VLNC cigarettes only; (3) VLNC cigarettes plus e-cigarettes with classic TF (hereafter, VLNC + TF); and (4) VLNC cigarettes plus e-cigarettes with preferred flavors (hereafter, VLNC + PF). Interventions: The NNC cigarettes contained 15.8 mg nicotine/g tobacco, the VLNC cigarettes contained 0.4 mg nicotine/g tobacco, the VLNC + TF had pods containing 5% nicotine by weight and only classic TF, and the VLNC + PF had pods containing 5% nicotine in 8 flavors (including fruity and sweet) from which participants selected 3 flavors. Main Outcomes and Measures: The primary outcome was mean total cigarettes smoked per day (CPD) during week 16. Tobacco-related biomarkers were assessed, including total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a tobacco-specific carcinogen. Results: A total of 326 participants (mean [SD] age, 40.09 [10.79] years; 243 females [74.5%]) from 3 randomized clinical trials were included. The VLNC cigarettes decreased total CPD, with least square (LS) means (SEMs) of 22.54 (1.59) in the NNC, 14.32 (1.32) in the VLNC, 11.76 (1.18) in the VLNC + TF, and 7.63 (0.90) in the VLNC + PF conditions. Each VLNC condition differed significantly from NNC, with an adjusted mean difference (AMD) of -8.21 (95% CI, -12.27 to -4.16; P < .001) in the VLNC, -10.78 (95% CI, -14.67 to -6.90; P < .001) in the VLNC + TF, and -14.91 (95% CI, -18.49 to -11.33; P < .001) in the VLNC + PF conditions. Participants in the VLNC + PF condition also decreased smoking below the VLNC and the VLNC + TF conditions (AMDs, -6.70 [95% CI, -9.84 to -3.55; P < .001] and -4.13 [95% CI, -7.05 to -1.21; P = .02]); the VLNC and VLNC + TF conditions did not differ significantly. Consistent with decreases in CPD, NNAL levels in the VLNC + PF condition were lower than in all other conditions, with AMDs (in pmol/mg creatinine) of -0.94 (95% CI, -1.41 to -0.47; P < .001) compared with the NNC condition, -0.47 (95% CI, -0.87 to -0.08; P = .03) compared with the VLNC condition, and -0.46 (95% CI, -0.83 to -0.10; P = .04) compared with the VLNC + TF condition. Conclusions and Relevance: These results provide further evidence that a reduced-nicotine standard for cigarettes has the potential to decrease smoking and tobacco-toxicant exposure in high-risk populations and that these effects may be enhanced when adults can access e-cigarettes in commonly preferred flavors. Trial Registration: ClinicalTrials.gov Identifiers: NCT04092387, NCT04090879, NCT04092101.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Humanos , Feminino , Adulto , Masculino , Nicotina/administração & dosagem , Pessoa de Meia-Idade , Abandono do Hábito de Fumar/métodos , Abandono do Hábito de Fumar/psicologia , Produtos do Tabaco , AromatizantesRESUMO
SIGNIFICANCE: A growing number of adults use more than one tobacco product, with dual use of cigarettes and e-cigarettes being the most common combination. Monitoring sex disparities in tobacco use is a public health priority. However, little is known regarding whether dual users differ by sex. METHODS: Data came from Waves 4-6 (12/2016-11/2021) of the Population Assessment of Tobacco and Health Study, a US nationally-representative longitudinal survey. This analysis included current adult dual users of cigarettes and e-cigarettes. We used weighted generalized estimating equations to assess the association between sex and (1) making a cigarette quit attempt (n = 1882 observations from n = 1526 individuals) and (2) smoking cessation (n = 2081 observations from n = 1688 individuals) across two wave pairs, adjusting for age, education, ethnicity, time-to-first cigarette after waking, and e-cigarette use frequency. RESULTS: Among US dual users, 14.1% (95% Confidence Intervals [Cl] = 11.9-16.4) of females and 23.4% (20.0-26.9) of males were young adults (aged 18-24), 11.7% (9.2-14.2) of females and 14.4% (11.6-17.2) of males had
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In 2023, the Faculty of Dental Medicine, Saint Joseph University of Beirut (USJ) celebrated its 100th anniversary, marking a century of unwavering commitment to academic excellence. This milestone offers a valuable opportunity to navigate the history and evolution of dentistry in Lebanon, from its ancient roots in Phoenicia to its modern developments. It chronicles the transformative journey of dentistry while recognizing the key role played against all odds by the Society of Jesus and Saint Joseph University of Beirut in fostering the growth of dentistry as a distinct medical discipline.
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História da Odontologia , Líbano , História do Século XX , História Antiga , História do Século XIX , História do Século XXI , Faculdades de Odontologia/história , História do Século XVIII , HumanosRESUMO
SIGNIFICANCE: A growing number of adults use more than one tobacco product, with dual use of cigarettes and e-cigarettes being the most common combination. Monitoring sex disparities in tobacco use is a public health priority. However, little is known regarding whether dual users differ by sex. METHODS: Data came from Waves 4-6 (12/2016-11/2021) of the Population Assessment of Tobacco and Health Study, a US nationally-representative longitudinal survey. This analysis included current adult dual users of cigarettes and e-cigarettes. We used weighted generalized estimating equations to assess the association between sex and (1) making a cigarette quit attempt (n = 1882 observations from n = 1526 individuals) and (2) smoking cessation (n = 2081 observations from n = 1688 individuals) across two wave pairs, adjusting for age, education, ethnicity, time-to-first cigarette after waking, and e-cigarette use frequency. RESULTS: Among US dual users, 14.1% (95% Confidence Intervals [Cl] = 11.9-16.4) of females and 23.4% (20.0-26.9) of males were young adults (aged 18-24), 11.7% (9.2-14.2) of females and 14.4% (11.6-17.2) of males had Assuntos
Sistemas Eletrônicos de Liberação de Nicotina
, Abandono do Hábito de Fumar
, Humanos
, Masculino
, Feminino
, Abandono do Hábito de Fumar/estatística & dados numéricos
, Estudos Longitudinais
, Adulto
, Estados Unidos/epidemiologia
, Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos
, Pessoa de Meia-Idade
, Fatores Sexuais
, Uso de Tabaco/epidemiologia
, Adolescente
, Adulto Jovem
, Produtos do Tabaco/estatística & dados numéricos
, Fumar Cigarros/epidemiologia
, Vaping/epidemiologia
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Adverse side effects from pharmacological treatments cause people with migraine to delay or avoid taking medication. Exercise is effective, but the effect of environment is unknown. The purpose was to determine if a natural environment affects monthly migraine load. Sedentary individuals (8 female, 1 non-binary) who experienced migraines participated. Participants completed one month of exercise (3 x week, 30-min, 60-70% estimated HRmax) indoors as well as in a natural outdoor environment in a randomized counterbalanced order. Migraine load was determined using the Headache Impact Test (HIT-6) and Migraine Disability Assessment (MIDAS) at the beginning and end of each month. Data were analyzed using repeated measures ANOVA. No interactions were evident for HIT-6 (p = 0.80), MIDAS (p = 0.72), migraine days (p = 0.508), or pain intensity (p = 0.66). No main effects were noted. Compliance was greater in the outdoor environment, with more exercise sessions completed in nature (Indoor = 72%, Outdoor = 90%, p < 0.001). Exercise environment did not impact MIDAS or HIT-6 questionnaire results, number of migraine days, or pain intensity. While there was no reduction in migraine load, it is possible that other health benefits were experienced due to greater compliance in a natural environment.
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Estudos Cross-Over , Terapia por Exercício , Transtornos de Enxaqueca , Cooperação do Paciente , Humanos , Transtornos de Enxaqueca/terapia , Feminino , Masculino , Adulto , Terapia por Exercício/métodos , Projetos Piloto , Pessoa de Meia-Idade , Meio Ambiente , Doença Crônica , Medição da DorRESUMO
OBJECTIVES: Women represent >50% of people with HIV globally but have historically been underrepresented in clinical trials. We evaluated the efficacy and safety of switching to dolutegravir/lamivudine (DTG/3TC) vs continuing their current antiretroviral regimen (CAR) by sex assigned at birth (female and male) in virologically suppressed adults with HIV-1 without prior virological failure in a pooled analysis of two randomized controlled trials. METHODS: This analysis included 48-week data from the phase 3 TANGO and SALSA studies. Primary and key secondary endpoints included proportions of participants with HIV-1 RNA ≥50 and <50 copies/mL at week 48, respectively. Safety was also assessed. RESULTS: Of 1234 participants, 250 (DTG/3TC, n = 133; CAR, n = 117) were female at birth. Week 48 proportions of participants with Snapshot HIV-1 RNA ≥50 copies/mL were similar regardless of sex at birth (DTG/3TC vs CAR: female, <1% [1/133] vs 2% [2/117]; male, <1% [1/482] vs <1% [3/502]). Proportions with HIV-1 RNA <50 copies/mL were high across sexes and treatment groups (DTG/3TC vs CAR: female, 91% [121/133] vs 89% [104/117]; male, 94% [455/482] vs 94% [471/502]). Immunological response with DTG/3TC was slightly higher in female participants. Incidences of adverse events leading to withdrawal and serious adverse events were low and comparable between treatment groups and across sexes. Weight gain was higher with DTG/3TC than with CAR among female participants aged ≥50 years (treatment difference 2.08 kg [95% confidence interval 0.40-3.75]). CONCLUSIONS: Results confirm the robustness of DTG/3TC as a switch option in virologically suppressed females with HIV-1, with outcomes similar to those in males.
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Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Compostos Heterocíclicos com 3 Anéis , Lamivudina , Oxazinas , Piperazinas , Piridonas , Humanos , Piridonas/uso terapêutico , Oxazinas/uso terapêutico , Feminino , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Lamivudina/efeitos adversos , Piperazinas/uso terapêutico , Masculino , Adulto , HIV-1/efeitos dos fármacos , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Pessoa de Meia-Idade , Carga Viral , Resultado do Tratamento , Fatores Sexuais , RNA ViralRESUMO
This article considers the addition of comprehensive 24-chromosomal microarray (CMA) analysis of products of conception (POC) to a standard evaluation for recurrent pregnancy loss (RPL) to help direct treatment towards expectant management versus IVF with preimplantation genetic testing for aneuploidies (PGT-A). The review included retrospective data from 65,333 miscarriages, a prospective evaluation of 378 couples with RPL who had CMA testing of POC and the standard workup, and data from an additional 1020 couples who were evaluated for RPL but did not undergo CMA testing of POC. Aneuploidy in POC explained the pregnancy loss in 57.7% (218/378) of cases. In contrast, the full RPL evaluation recommended by the American Society for Reproductive Medicine identified a potential cause in only 42.9% (600/1398). Combining the data from the RPL evaluation and the results of genetic testing of POC provides a probable explanation for the loss in over 90% (347/378) of women. Couples with an unexplained loss after the standard evaluation with POC aneuploidy accounted for 41% of cases; PGT-A may be considered after expectant management. Conversely, PGT-A would have a limited role in those with a euploid loss and a possible explanation after the standard workup. Categorizing a pregnancy loss as an explained versus unexplained loss after the standard evaluation combined with the results of CMA testing of POC may help identify patients who would benefit from expectant management versus PGT-A.
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Aborto Habitual , Aneuploidia , Testes Genéticos , Diagnóstico Pré-Implantação , Humanos , Feminino , Gravidez , Testes Genéticos/métodos , Aborto Habitual/genética , Masculino , Estudos Retrospectivos , Fertilização/genéticaRESUMO
OBJECTIVE: Reducing harm from combustible cigarette use among women of reproductive age (WRA) is critical given their potential vulnerability to multigenerational adverse impacts of cigarette smoking. Although electronic nicotine delivery systems (ENDS) are not approved smoking cessation aids in the US, many WRA who smoke report using ENDS to help quit smoking. Associations between ENDS use patterns and smoking-cessation efforts among US WRA remain unclear. METHODS: Using the Population Assessment of Tobacco and Health (PATH) Study, we examined whether baseline (Wave 3 or 4) ENDS use frequency predicted (a) making a cigarette quit attempt (QA) and (b) successful quitting by follow-up (Wave 4 or 5, respectively) among WRA (N = 2834; 72.1% non-Hispanic White). RESULTS: Daily ENDS use predicted greater adjusted odds of making a QA than non-daily (AOR = 1.63, 95% CI = 1.03, 2.59) and no ENDS use (AOR = 1.97, 95% CI = 1.23, 3.14), and greater odds of successful smoking cessation than non-daily use (AOR = 2.37, 95% CI = 1.31, 4.26). Daily ENDS use did not significantly improve odds of successful smoking cessation compared to no ENDS use (AOR = 1.62, 95% CI = 0.97, 2.69). Non-daily ENDS use did not significantly improve odds of making a QA (AOR = 1.21, 95% CI = 0.94, 1.56) and hindered successful smoking cessation compared to no ENDS use (AOR = 0.68, 95% CI = 0.48, 0.98). CONCLUSIONS: These findings suggest that benefits of ENDS for smoking cessation in WRA may be greatest among those who use ENDS daily. WRA who choose to use ENDS to help quit would be well-informed by evidence that non-daily ENDS use may impede smoking cessation.
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Dengue is the most prevalent mosquito-borne viral disease and a major public health problem worldwide. Most primary infections with the four dengue virus serotypes (DENV1-4) are inapparent; nonetheless, whether the distribution of symptomatic versus inapparent infections by serotype varies remains unknown. Here, we present (1) the evaluation of a multiplex DENV1-4 envelope domain III multiplex microsphere-based assay (EDIII-MMBA) to serotype inapparent primary infections and (2) its application leveraging 17 years of prospective sample collection from the Nicaraguan Pediatric Dengue Cohort Study (PDCS). First, we evaluated the performance of the EDIII-MMBA with samples characterized by RT-PCR or focus reduction neutralization test. Next, we analyzed 46% (N=574) of total inapparent primary DENV infections in the PDCS with the EDIII-MMBA to evaluate the epidemiology of inapparent infections. Remaining infections were inferred using stochastic imputation, taking year and neighborhood into account. Infection incidence and percentage of inapparent, symptomatic, and severe infections were analyzed by serotype. The EDIII-MMBA demonstrated excellent overall accuracy (100%, 95.8-100%) for serotyping symptomatic and inapparent primary DENV infections when evaluated against gold-standard serotyping methods. We found that a significant majority of primary infections were inapparent, with DENV3 exhibiting the highest likelihood of symptomatic and severe primary infections (Pooled OR compared to DENV1 = 2.13, 95% CI 1.28-3.56, and 6.75, 2.01-22.62, respectively), whereas DENV2 was similar to DENV1 in both analyses. Significant within- and between-year variation in serotype distribution between symptomatic and inapparent infections and circulation of serotypes undetected in symptomatic cases were observed in multiple years. Our study indicates that case surveillance skews the perceived epidemiological footprint of DENV. We reveal a more complex and intricate pattern of serotype distribution in inapparent infections. The significant differences in infection outcomes by serotype emphasizes the need for vaccines with balanced immunogenicity and efficacy across serotypes.
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Ubiquitin ligation is typically executed by hallmark E3 catalytic domains. Two such domains, 'cullin-RING' and 'RBR', are individually found in several hundred human E3 ligases, and collaborate with E2 enzymes to catalyze ubiquitylation. However, the vertebrate-specific CUL9 complex with RBX1 (also called ROC1), of interest due to its tumor suppressive interaction with TP53, uniquely encompasses both cullin-RING and RBR domains. Here, cryo-EM, biochemistry and cellular assays elucidate a 1.8-MDa hexameric human CUL9-RBX1 assembly. Within one dimeric subcomplex, an E2-bound RBR domain is activated by neddylation of its own cullin domain and positioning from the adjacent CUL9-RBX1 in trans. Our data show CUL9 as unique among RBX1-bound cullins in dependence on the metazoan-specific UBE2F neddylation enzyme, while the RBR domain protects it from deneddylation. Substrates are recruited to various upstream domains, while ubiquitylation relies on both CUL9's neddylated cullin and RBR domains achieving self-assembled and chimeric cullin-RING/RBR E3 ligase activity.
Assuntos
Microscopia Crioeletrônica , Proteínas Culina , Enzimas de Conjugação de Ubiquitina , Ubiquitinação , Humanos , Proteínas de Transporte/metabolismo , Proteínas de Transporte/química , Proteínas de Transporte/genética , Proteínas Culina/metabolismo , Proteínas Culina/química , Células HEK293 , Modelos Moleculares , Proteína NEDD8/metabolismo , Proteína NEDD8/genética , Proteína NEDD8/química , Ligação Proteica , Multimerização Proteica , Enzimas de Conjugação de Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/química , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/genéticaRESUMO
Social jet lag (SJL) is a misalignment between sleep and wake times on workdays and free days. SJL leads to chronic circadian rhythm disruption and may affect nearly 70% of the general population, leading to increased risk for cardiometabolic diseases. This study investigated the effects of SJL on metabolic health, exercise performance, and exercise-induced skeletal muscle adaptations in mice. Ten-week-old C57BL/6J mice (n = 40) were allocated to four groups: control sedentary (CON-SED), control exercise (CON-EX), social jet lag sedentary (SJL-SED), and social jet lag exercise (SJL-EX). CON mice were housed under a 12:12-h light-dark cycle. SJL was simulated by implementing a 4-h phase delay for 3 days to simulate "weekends," followed by a 4-h phase advance back to "weekdays," for 6 wk. EX mice had free access to a running wheel. Graded exercise tests (GXTs) and glucose tolerance tests (GTTs) were performed at baseline and after intervention to monitor the effects of exercise and social jet lag on cardiorespiratory and metabolic health, respectively. SJL led to alterations in activity and running patterns and clock gene expression in skeletal muscle and decreased average running distance (P < 0.05). SJL-SED mice gained significantly more weight compared with CON-SED and SJL-EX mice (P < 0.01). SJL impaired fasting blood glucose and glucose tolerance compared with CON mice (P < 0.05), which was partially restored by exercise in SJL-EX mice. SJL also blunted improvements in exercise performance and mitochondrial content in the quadriceps. These data suggest that SJL blunted some cardiometabolic adaptations to exercise and that proper circadian hygiene is necessary for maintaining health and performance.NEW & NOTEWORTHY In mice, disrupting circadian rhythms with social jet lag for 6 wk caused significant weight gain, higher fasting blood glucose, and impaired glucose tolerance compared with control. Voluntary exercise in mice experiencing social jet lag prevented weight gain, though the mice still experienced increased fasting blood glucose and impaired exercise performance compared with trained mice not experiencing social jet lag. Social jet lag seems to be a potent circadian rhythm disruptor that impacts exercise-induced training adaptations.
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Doenças Cardiovasculares , Síndrome do Jet Lag , Humanos , Camundongos , Animais , Síndrome do Jet Lag/genética , Glicemia , Camundongos Endogâmicos C57BL , Ritmo Circadiano/fisiologia , Aumento de PesoRESUMO
Circular RNAs (circRNAs), covalently closed RNA molecules that form due to back-splicing of RNA transcripts, have recently been implicated in Alzheimer's disease and related tauopathies. circRNAs are regulated by N6-methyladenosine (m6A) RNA methylation, can serve as "sponges" for proteins and RNAs, and can be translated into protein via a cap-independent mechanism. Mechanisms underlying circRNA dysregulation in tauopathies and causal relationships between circRNA and neurodegeneration are currently unknown. In the current study, we aimed to determine whether pathogenic forms of tau drive circRNA dysregulation and whether such dysregulation causally mediates neurodegeneration. We identify circRNAs that are differentially expressed in the brain of a Drosophila model of tauopathy and in induced pluripotent stem cell (iPSC)-derived neurons carrying a tau mutation associated with autosomal dominant tauopathy. We leverage Drosophila to discover that depletion of circular forms of muscleblind (circMbl), a circRNA that is particularly abundant in brains of tau transgenic Drosophila, significantly suppresses tau neurotoxicity, suggesting that tau-induced circMbl elevation is neurotoxic. We detect a general elevation of m6A RNA methylation and circRNA methylation in tau transgenic Drosophila and find that tau-induced m6A methylation is a mechanistic driver of circMbl formation. Interestingly, we find that circRNA and m6A RNA accumulate within nuclear envelope invaginations of tau transgenic Drosophila and in iPSC-derived cerebral organoid models of tauopathy. Taken together, our studies add critical new insight into the mechanisms underlying circRNA dysregulation in tauopathy and identify m6A-modified circRNA as a causal factor contributing to neurodegeneration. These findings add to a growing literature implicating pathogenic forms of tau as drivers of altered RNA metabolism.
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OBJECTIVE: To evaluate sleep deprivation effects on the acute physiological response to a combined stressor of woodsmoke and exercise. METHODS: Ten participants completed two exercise trials (8 hours of sleep vs 4 hours) with woodsmoke. Trials were conducted in a crossover design. Key measures examined before and after each trial included heart rate variability, pulse wave velocity, blood pressure, pulmonary function testing, and oxidative stress. RESULTS: Acute sleep deprivation experienced before exercise and woodsmoke exposure did not impact metrics of heart rate variability, pulse wave velocity, pulmonary function testing, blood pressure, or oxidative stress. CONCLUSIONS: Acute sleep deprivation did not amplify physiologic metrics in response to moderate-intensity aerobic exercise with inhaled woodsmoke. Although findings do not eliminate the negative impacts of inhaling woodsmoke, more research is needed to understand the acute effects of woodsmoke exposure on the cardiovascular system. 1.
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Pressão Sanguínea , Estudos Cross-Over , Exercício Físico , Frequência Cardíaca , Privação do Sono , Fumaça , Madeira , Humanos , Privação do Sono/fisiopatologia , Masculino , Frequência Cardíaca/fisiologia , Adulto , Exercício Físico/fisiologia , Pressão Sanguínea/fisiologia , Fumaça/efeitos adversos , Feminino , Estresse Oxidativo , Adulto Jovem , Análise de Onda de Pulso , Testes de Função RespiratóriaRESUMO
The University of Michigan created the Practice-Oriented Research Training (PORT) program and implemented it between 2008 and 2018. The PORT program provided research training and funding opportunities for allied healthcare professionals. The program consisted of weekly didactics and group discussion related to topics relevant to developing specific research ideas into projects and funding for a mentored research project for those who submitted a competitive grant application. The goal of this evaluation was to assess the long-term impact of the PORT program on the research careers of the participants. Ninety-two participants (74 staff and 18 faculty) participated in both phases of the program. A mixed-methods approach to evaluation was used; 25 participants who received funding for their research completed surveys, and semi-structured interviews were conducted with eight program participants. In addition, data were collected on participants' publication history. Fifteen out of the 74 staff participants published 31 first-authored papers after participating in PORT. Twelve out of 15 staff participants who published first-authored papers did so for the first time after participating in the PORT program. Results of quantitative and qualitative analyses suggest that the PORT program had positive impacts on both participants and the research community.
RESUMO
OBJECTIVES: Assessing dienogest's efficacy in endometriosis patients undergoing in vitro fertilization (IVF). DATA SOURCES: Systematic search in databases (PubMed, MEDLINE, Embase, Web of Science, Cochrane CENTRAL, Google Scholar) until 1 October 2022. STUDY SELECTIONS: Randomized trials and observational studies comparing extended dienogest pre-treatment, no pre-treatment, or gonadotropin-releasing hormone (GnRH) agonist pre-treatment in endometriosis-linked IVF. OUTCOME MEASURES: live birth, clinical pregnancy rates, oocytes collected, miscarriage rate, gonadotropin consumption. DATA EXTRACTIONS AND SYNTHESES: Two authors independently assessed eligibility. Dichotomous variables were analyzed via a random-effect model and Mantel-Haenszel method to calculate weighted estimates and 95% confidence intervals (CI). I2 statistic gauged study heterogeneity; GRADE criteria evaluated evidence quality. CONCLUSIONS: Out of 191 publications, five studies with 723 participants were included. Uncertainty persists on whether prolonged dienogest affects live birth (RR 1.42, 95% CI 0.29 to 6.84; 3 studies, n = 289; I2 86%) and clinical pregnancy rates (RR 1.33, 95% CI 0.31 to 5.65; 3 studies, n = 289; I2 86%) compared to conventional IVF. Moreover, uncertainty remains regarding intervention impact on live birth (RR 1.46, 95% CI 0.63 to 3.37; 1 study, n = 34) and clinical pregnancy rates (RR 1.32, 95% CI 0.78 to 2.23; 3 studies, n = 288; I2 0%) versus long-term GnRH agonist therapy before IVF. Given limited data and very low evidence quality, doubts arise about the benefits of long-term dienogest pre-treatment before conventional IVF in endometriosis patients.