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Many autism spectrum disorder (ASD)-associated genes act as transcriptional regulators (TRs). Chromatin immunoprecipitation sequencing (ChIP-seq) was used to identify the regulatory targets of ARID1B, BCL11A, FOXP1, TBR1, and TCF7L2, ASD-associated TRs in the developing human and mouse cortex. These TRs shared substantial overlap in the binding sites, especially within open chromatin. The overlap within a promoter region, 1-2,000 bp upstream of the transcription start site, was highly predictive of brain-expressed genes. This signature was observed in 96 out of 102 ASD-associated genes. In vitro CRISPRi against ARID1B and TBR1 delineated downstream convergent biology in mouse cortical cultures. After 8 days, NeuN+ and CALB+ cells were decreased, GFAP+ cells were increased, and transcriptomic signatures correlated with the postmortem brain samples from individuals with ASD. We suggest that functional convergence across five ASD-associated TRs leads to shared neurodevelopmental outcomes of haploinsufficient disruption.
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Encéfalo , Humanos , Animais , Camundongos , Encéfalo/metabolismo , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/patologia , Transtorno Autístico/genética , Transtorno Autístico/metabolismo , Transtorno Autístico/patologia , Regulação da Expressão Gênica , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Loci GênicosRESUMO
This study compares the race and ethnicity of reproductive-age females between states that implemented restrictive abortion policies after the Dobbs v Jackson Women's Health Organization decision and states that did not.
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Etnicidade , Feminino , Humanos , Estados Unidos , Gravidez , Adulto , Aborto Induzido/legislação & jurisprudência , Aborto Induzido/estatística & dados numéricos , Grupos Raciais , Adolescente , Adulto Jovem , Aborto Legal/legislação & jurisprudência , Governo EstadualRESUMO
We explored the association between the use of a hospital-based food pantry and subsequent emergency department (ED) utilization among Medicaid patients with diabetes in a large safety-net health system. Leveraging 2015-2019 electronic health record data, we used a staggered difference-in-differences approach to measure changes in ED use before vs after food pantry use. Food pantry use was associated with a 7.3 percentage point decrease per patient per quarter (95% confidence interval, -13.8 to -0.8) in the probability of subsequent ED utilization ( P = .03). Addressing food insecurity through hospital-based food pantries may be one mechanism for reducing ED use among low-income patients with diabetes.
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Diabetes Mellitus , Serviço Hospitalar de Emergência , Medicaid , Humanos , Estados Unidos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Masculino , Diabetes Mellitus/terapia , Pessoa de Meia-Idade , Adulto , Assistência Alimentar , Insegurança Alimentar , Provedores de Redes de SegurançaRESUMO
Management of cancer during pregnancy requires careful consideration of risks and benefits from maternal and fetal perspectives. For advanced lung adenocarcinomas, with no targetable driver mutations, there is evidence-based guidance on the use of carboplatin-paclitaxel chemotherapy after first trimester. In contrast, for epidermal growth factor receptor (EGFR)-mutated or anaplastic lymphoma kinase (ALK)-rearranged metastatic lung adenocarcinomas, there is a paucity of clinical data on the safety of EGFR and ALK tyrosine kinase inhibitors to mother and fetus for official guidelines to recommend the use of these otherwise-first-line therapies in pregnancy. Considering this knowledge gap, we present a case of a young gravida 1 para 0 (G1P0) woman who continued alectinib 300 mg oral two times per day for ALK-rearranged metastatic lung adenocarcinoma throughout all 36 weeks of her pregnancy and delivered a healthy baby at term via caesarean section (C-section).
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Adenocarcinoma de Pulmão , Antineoplásicos , Carbazóis , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Piperidinas , Gravidez , Humanos , Feminino , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quinase do Linfoma Anaplásico/genética , Neoplasias Pulmonares/patologia , Cesárea , Receptores Proteína Tirosina Quinases/metabolismo , Antineoplásicos/uso terapêutico , Adenocarcinoma de Pulmão/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Receptores ErbB/genéticaRESUMO
This paper describes the analysis of electrodermal activity (EDA) in the context of students' scholastic activity. Taking a multidisciplinary, citizen science and maker-centric approach, low-cost, bespoken wearables, such as a mini weather station and biometric wristband, were built. To investigate both physical health as well as stress, the instruments were first validated against research grade devices. Following this, a research experiment was created and conducted in the context of students' scholastic activity. Data from this experiment were used to train machine learning models, which were then applied to interpret the relationships between the environment, health, and stress. It is hoped that analyses of EDA data will further strengthen the emerging model describing the intersections between local microclimate and physiological and neurological stress. The results suggest that temperature and air quality play an important role in students' physiological well-being, thus demonstrating the feasibility of understanding the extent of the effects of various microclimatic factors. This highlights the importance of thermal comfort and air ventilation in real-life applications to improve students' well-being. We envision our work making a significant impact by showcasing the effectiveness and feasibility of inexpensive, self-designed wearable devices for tracking microclimate and electrodermal activity (EDA). The affordability of these wearables holds promising implications for scalability and encourages crowd-sourced citizen science in the relatively unexplored domain of microclimate's influence on well-being. Embracing citizen science can then democratize learning and expedite rapid research advancements.
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BACKGROUND: 25-hydroxyvitamin D can undergo C-3 epimerization to produce 3-epi-25(OH)D3. 3-epi-25(OH)D3 levels decline in chronic kidney disease (CKD), but its role in regulating the cardiovascular system is unknown. Herein, we examined the relationship between 3-epi-25(OH)D3, and cardiovascular functional and structural endpoints in patients with CKD. METHODS: We examined n = 165 patients with advanced CKD from the Cardiopulmonary Exercise Testing in Renal Failure and After Kidney Transplantation (CAPER) study cohort, including those who underwent kidney transplant (KTR, n = 76) and waitlisted patients who did not (NTWC, n = 89). All patients underwent cardiopulmonary exercise testing and echocardiography at baseline, 2 months and 12 months. Serum 3-epi-25(OH)D3 was analyzed by liquid chromatography-tandem mass spectrometry. RESULTS: Patients were stratified into quartiles of baseline 3-epi-25(OH)D3 (Q1: <0.4 ng/mL, n = 51; Q2: 0.4 ng/mL, n = 26; Q3: 0.5-0.7 ng/mL, n = 47; Q4: ≥0.8 ng/mL, n = 41). Patients in Q1 exhibited lower peak oxygen uptake [VO2Peak = 18.4 (16.2-20.8) mL/min/kg] compared with Q4 [20.8 (18.6-23.2) mL/min/kg; P = .009]. Linear mixed regression model showed that 3-epi-25(OH)D3 levels increased in KTR [from 0.47 (0.30) ng/mL to 0.90 (0.45) ng/mL] and declined in NTWC [from 0.61 (0.32) ng/mL to 0.45 (0.29) ng/mL; P < .001]. Serum 3-epi-25(OH)D3 was associated with VO2Peak longitudinally in both groups [KTR: ß (standard error) = 2.53 (0.56), P < .001; NTWC: 2.73 (0.70), P < .001], but was not with left ventricular mass or arterial stiffness. Non-epimeric 25(OH)D3, 24,25(OH)2D3 and the 25(OH)D3:24,25(OH)2D3 ratio were not associated with any cardiovascular outcome (all P > .05). CONCLUSIONS: Changes in 3-epi-25(OH)D3 levels may regulate cardiovascular functional capacity in patients with advanced CKD.
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Sistema Cardiovascular , Transplante de Rim , Insuficiência Renal Crônica , Humanos , Vitamina D , Vitaminas , Insuficiência Renal Crônica/cirurgiaRESUMO
PURPOSE: We investigated the association of MRI findings in men with a previous diagnosis of atypical small acinar proliferation (ASAP) or multifocal high-grade intraepithelial neoplasia (HGPIN) with pathologic findings on repeat biopsy. MATERIALS AND METHODS: We retrospectively reviewed patients with ASAP/multifocal HGPIN undergoing a repeat biopsy in the Michigan Urological Surgery Improvement Collaborative registry. We included men with and without an MRI after the index biopsy demonstrating ASAP/multifocal HGPIN but before the repeat biopsy. Men with an MRI prior to the index biopsy were excluded. We compared the proportion of men with ≥ GG2 CaP (Grade Group 2 prostate cancer) on repeat biopsy among the following groups with the χ2 test: no MRI, PIRADS (Prostate Imaging-Reporting and Data System) ≥ 4, and PIRADS ≤ 3. Multivariable models were used to estimate the adjusted association between MRI findings and ≥ GG2 CaP on repeat biopsy. RESULTS: Among the 207 men with a previous diagnosis of ASAP/multifocal HGPIN that underwent a repeat biopsy, men with a PIRADS ≥ 4 lesion had a higher proportion of ≥ GG2 CaP (56%) compared with men without an MRI (12%, P < .001). A lower proportion of men with PIRADS ≤ 3 lesions had ≥ GG2 CaP (3.0%) compared with men without an MRI (12%, P = .13). In the adjusted model, men with a PIRADS 4 to 5 lesion had higher odds (OR: 11.4, P < .001) of ≥ GG2 CaP on repeat biopsy. CONCLUSIONS: MRI is a valuable diagnostic tool to triage which men with a history of ASAP or multifocal HGPIN on initial biopsy should undergo or avoid repeat biopsy without missing clinically significant CaP.
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Neoplasia Prostática Intraepitelial , Neoplasias da Próstata , Masculino , Humanos , Neoplasia Prostática Intraepitelial/diagnóstico por imagem , Neoplasia Prostática Intraepitelial/patologia , Estudos Retrospectivos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Biópsia , Imageamento por Ressonância Magnética , Proliferação de CélulasRESUMO
Patients with chronic kidney disease (CKD) are often regarded as experiencing wasting of muscle mass and declining muscle strength and function, collectively termed sarcopenia. The extent of skeletal muscle wasting in clinical and preclinical CKD populations is unclear. We evaluated skeletal muscle atrophy in preclinical and clinical models of CKD, with multiple sub-analyses for muscle mass assessment methods, CKD severity, sex and across the different preclinical models of CKD. We performed a systematic literature review of clinical and preclinical studies that measured muscle mass/size using the following databases: Ovid Medline, Embase and Scopus. A random effects meta-analysis was utilized to determine standard mean difference (SMD; Hedges' g) between healthy and CKD. Heterogeneity was evaluated using the I2 statistic. Preclinical study quality was assessed via the Systematic Review Centre for Laboratory Animal Experimentation and clinical studies quality was assessed via the Newcastle-Ottawa Scale. This study was registered in PROSPERO (CRD42020180737) prior to initiation of the search. A total of 111 studies were included in this analysis using the following subgroups: 106 studies in the primary CKD analysis, 18 studies that accounted for diabetes and 7 kidney transplant studies. Significant atrophy was demonstrated in 78% of the preclinical studies and 49% of the clinical studies. The random effects model demonstrated a medium overall SMD (SMD = 0.58, 95% CI = 0.52-0.64) when combining clinical and preclinical studies, a medium SMD for the clinical population (SMD = 0.48, 95% CI = 0.42-0.55; all stages) and a large SMD for preclinical CKD (SMD = 0.95, 95% CI = 0.76-1.14). Further sub-analyses were performed based upon assessment methods, disease status and animal model. Muscle atrophy was reported in 49% of the clinical studies, paired with small mean differences. Preclinical studies reported significant atrophy in 78% of studies, with large mean differences. Across multiple clinical sub-analyses such as severity of CKD, dialysis modality and diabetes, a medium mean difference was found. Sub-analyses in both clinical and preclinical studies found a large mean difference for males and medium for females suggesting sex-specific implications. Muscle atrophy differences varied based upon assessment method for clinical and preclinical studies. Limitations in study design prevented conclusions to be made about the extent of muscle loss with disease progression, or the impact of dialysis. Future work would benefit from the use of standardized measurement methods and consistent clinical staging to improve our understanding of atrophy changes in CKD progression, and analysis of biological sex differences.
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Diabetes Mellitus , Insuficiência Renal Crônica , Humanos , Feminino , Masculino , Atrofia Muscular/etiologia , Diálise Renal , Músculo Esquelético/fisiologiaRESUMO
INTRODUCTION: The incidence of kidney stones in the United States continues to increase. Although dietary interventions have shown to be effective in reducing stone events, adherence to medical management continues to be a limiting factor. For that reason, patient education has become a focus of many physicians. TikTok, a social media application with over one billion users worldwide, has emerged as an online center for medical knowledge sharing by physicians and non-physicians alike. TikTok users share kidney stone prevention information through short informational videos directly to the general public. Little is known regarding the quality of medical advice provided in these videos. The purpose of this study was to evaluate the reach and quality of kidney stone prevention information on TikTok. METHODS: We conducted a cross-sectional analysis of renal stone prevention content on TikTok utilizing the search term #kidneystoneprevention to assess all the videos appearing on October 10th, 2022. Only videos in English, related to the topic, and with >1000 views were included. Videos were analyzed for descriptive statistics, including views, uploader profession, and stone prevention recommendations. Videos were assessed utilizing Denver International Study Center of Evaluative Rating of Information (DISCERN), a questionnaire used to appraise the quality of consumer health information (maximum score of 80 per video). The one-way analysis of variance (ANOVA) was used to determine statistical significance groups. RESULTS: Out of a total of 131 videos, 87 fit the inclusion criteria, resulting in a total of 8.75 million views. An average DISCERN score of 27.0 was observed. Only eight videos were published by physicians, of which the average DISCERN score of 35.3 was significantly greater than an average score of 26.2 for non-physicians (p<0.05). The most common recommendation was increased fluid intake (38.0%) followed by monitoring calcium levels (9.02%) and decreasing oxalate-rich foods (9.2%). CONCLUSIONS: Kidney stone prevention content on TikTok has a wide reach with millions of consumers. The majority of videos fail to match American Urological Association recommendations regarding diet therapies for stone prevention. Further research is needed to understand the extent of kidney stone prevention misinformation on social media and how it contributes to patient outcomes. Increased engagement in TikTok by urologists and health organizations may improve public education.
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Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Burkitt , Linfoma Difuso de Grandes Células B , Rituximab , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Vincristina/uso terapêutico , Resultado do TratamentoRESUMO
Patients with advanced chronic kidney disease (CKD) mostly die from sudden cardiac death and recurrent heart failure. The mechanisms of cardiac remodeling are largely unclear. To dissect molecular and cellular mechanisms of cardiac remodeling in CKD in an unbiased fashion, we performed left ventricular single-nuclear RNA sequencing in two mouse models of CKD. Our data showed a hypertrophic response trajectory of cardiomyocytes with stress signaling and metabolic changes driven by soluble uremia-related factors. We mapped fibroblast to myofibroblast differentiation in this process and identified notable changes in the cardiac vasculature, suggesting inflammation and dysfunction. An integrated analysis of cardiac cellular responses to uremic toxins pointed toward endothelin-1 and methylglyoxal being involved in capillary dysfunction and TNFα driving cardiomyocyte hypertrophy in CKD, which was validated in vitro and in vivo. TNFα inhibition in vivo ameliorated the cardiac phenotype in CKD. Thus, interventional approaches directed against uremic toxins, such as TNFα, hold promise to ameliorate cardiac remodeling in CKD.
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Insuficiência Cardíaca , Insuficiência Renal Crônica , Camundongos , Animais , Humanos , Fator de Necrose Tumoral alfa/genética , Toxinas Urêmicas , Remodelação Ventricular , Insuficiência Cardíaca/etiologiaRESUMO
Epidemiological studies have reported a strong association between circulating Klotho and physical function; however, the cohorts were comprised of older adults with multiple comorbidities. Herein, we examined the relationship between Klotho and physical function in a community-based cohort of healthy adults. In this cross-sectional study, serum Klotho was measured in 80 adults who visited the Musculoskeletal Function, Imaging, and Tissue Resource Core of the Indiana Center for Musculoskeletal Health. Participants (n = 20, 10 [50%] men per group) were chosen into four age groups: 20-34, 35-49, 50-64, and ≥ 65 years, and were further grouped based on performance (low vs. high) on grip strength and chair stand tests. Klotho levels were lower in the ≥ 65 years group (703.0 [189.3] pg/mL; p = 0.022) and the 50-64 years group (722.6 [190.5] pg/mL; p = 0.045) compared to 20-34 years (916.1 [284.8] pg/mL). No differences were observed in Klotho between the low and high performers. The ≥ 65 years group walked a shorter distance during the 6-min walk test (6MWT) compared to 20-34 years (p = 0.005). Klotho was correlated with age (p < 0.001), body fat (p = 0.037), and 6MWT distance (p = 0.022). Klotho levels decline as early as the fifth decade of life, potentially before the onset of age-related impairment in exercise capacity.
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Glucuronidase , Envelhecimento Saudável , Adulto , Idoso , Feminino , Humanos , Masculino , Adulto Jovem , Estudos Transversais , Força da Mão , CaminhadaRESUMO
OBJECTIVE: To summarize the current evidence and to make recommendations for antenatal fetal health surveillance (FHS) to detect perinatal risk factors and potential fetal decompensation in the antenatal period and to allow for timely intervention to prevent perinatal morbidity and/or mortality. TARGET POPULATION: Pregnant individuals with or without maternal, fetal, or pregnancy-associated perinatal risk factors for antenatal fetal decompensation. OPTIONS: To use basic and/or advanced antenatal testing modalities, based on risk factors for potential fetal decompensation. OUTCOMES: Early identification of potential fetal decompensation allows for interventions that may support fetal adaptation to maintain well-being or expedite delivery. BENEFITS, HARMS, AND COSTS: Antenatal FHS in pregnant individuals with identified perinatal risk factors may reduce the chance of adverse outcomes. Given the high false-positive rate, FHS may increase unnecessary interventions, which may result in harm, including parental anxiety, premature or operative birth, and increased use of health care resources. Optimization of surveillance protocols based on evidence-informed practice may improve perinatal outcomes and reduce harm. EVIDENCE: Medline, PubMed, Embase, and the Cochrane Library were searched from inception to January 2022, using medical subject headings (MeSH) and key words related to pregnancy, fetal monitoring, fetal movement, stillbirth, pregnancy complications, and fetal sonography. This document represents an abstraction of the evidence rather than a methodological review. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: All health care team members who provide care for or education to obstetrical patients, including maternal fetal medicine specialists, obstetricians, family physicians, midwives, nurses, nurse practitioners, and radiologists. SUMMARY STATEMENTS: RECOMMENDATIONS.
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Apêndice , Cuidado Pré-Natal , Feminino , Gravidez , Humanos , Feto , Parto , Monitorização FetalRESUMO
OBJECTIF: Résumer les données probantes actuelles et formuler des recommandations pour la surveillance prénatale du bien-être fÅtal afin de détecter les facteurs de risque périnatal et toute potentielle décompensation fÅtale et de permettre une intervention rapide en prévention de la morbidité et la mortalité périnatales. POPULATION CIBLE: Personnes enceintes avec ou sans facteurs maternels, fÅtaux ou gravidiques associés à des risques périnataux et à la décompensation fÅtale. OPTIONS: Utiliser des examens prénataux par technologie de base et/ou avancée en fonction des facteurs de risque de décompensation fÅtale. RéSULTATS: La reconnaissance précoce de toute décompensation fÅtale potentielle permet d'intervenir de façon à favoriser l'adaptation fÅtale pour maintenir le bien-être ou à accélérer l'accouchement. BéNéFICES, RISQUES ET COûTS: Chez les personnes enceintes ayant des facteurs de risque périnatal confirmés, la surveillance du bien-être fÅtal contribue à réduire le risque d'issue défavorable. Compte tenu du taux élevé de faux positifs, la surveillance du bien-être fÅtal peut augmenter le risque d'interventions inutiles, ce qui peut avoir des effets nuisibles, dont l'anxiété parentale, l'accouchement prématuré ou assisté et l'utilisation accrue des ressources de soins de santé. L'optimisation des protocoles de surveillance d'après des pratiques fondées sur des données probantes peut améliorer les issues périnatales et réduire les effets nuisibles. DONNéES PROBANTES: Des recherches ont été effectuées dans les bases de données Medline, PubMed, Embase et Cochrane Library, de leur création jusqu'à janvier 2022, à partir de termes MeSH et de mots clés liés à la grossesse, à la surveillance fÅtale, aux mouvements fÅtaux, à la mortinaissance, aux complications de grossesse et à l'échographie fÅtale. Le présent document est un résumé des données probantes et non pas une revue méthodologique. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations Assessment, Development and Evaluation). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et faibles). PROFESSIONNELS CONCERNéS: Tous les membres de l'équipe de soins qui prodiguent des soins ou donnent de l'information aux patientes en obstétrique, notamment les spécialistes en médecine fÅto-maternelle, les obstétriciens, les médecins de famille, les sages-femmes, les infirmières, les infirmières praticiennes et les radiologistes. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.
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The prognostic impact of t(11;14) in multiple myeloma (MM) needs to be better understood to inform future treatment decisions. The Australian Lymphoma Leukaemia Group embarked on a retrospective, observational cohort study using real-world data to interrogate treatment patterns and outcomes in 74 MM patients with t(11;14) [t(11;14)-MM] diagnosed over 10 years. This was compared to 159 and 111 MM patients with high-risk IgH translocations (IgH HR-MM) and hyperdiploidy (Hyperdiploid-MM), respectively, from the Australian Myeloma and Related Diseases Registry. No appreciable differences in age, gender, ISS, LDH levels, 1q21 or del(17p) status, or treatment patterns were observed between groups. Median PFS-1 was not different between groups but both t(11;14)-MM and IgH HR-MM had an inferior PFS-2 vs. Hyperdiploid-MM: median PFS-2 8.2 months, 10.0 months, and 19.8 months (p = 0.002), respectively. The 3-year OS were 69%, 71%, and 82% (p = 0.026), respectively. In the t(11;14)-MM group, gain or amplification of 1q21 at diagnosis predicted for poorer OS (HR 3.46, p = 0.002). Eleven patients had received venetoclax with 45% achieving better than a very good partial response. Results suggest that t(11;14) MM may confer an unfavorable risk profile and that the use of targeted therapies such as venetoclax earlier in the treatment algorithm should be explored.
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Objectives: Among critically ill patients, there is usually impairment of the hypothalamic-pituitary-adrenal axis, leading to a condition known as critical illness-related corticosteroid insufficiency (CIRCI). This investigation aims to determine the incidence of and characterize CIRCI among patients with COVID-19 as well as to analyze the outcomes of these critically ill patients. Methodology: This is a single-center, retrospective cohort study that investigated the occurrence of CIRCI among critically ill patients infected with COVID-19. Results: In this cohort, there were 145 COVID-19-positive patients with refractory shock, which reflects that 22.94% of the COVID-19 admissions have probable CIRCI.Patients who were given corticosteroids were found to have statistically significant longer median days on a ventilator (p=0.001). However, those on the corticosteroid arm were at higher risk of morbidity and mortality and a greater proportion had organ dysfunction. Multivariable logistic regression analysis revealed that SOFA score was a significant predictor of mortality in CIRCI (p=0.013). Conclusion: CIRCI has a unique presentation among patients with COVID-19 because of the presence of a high level of inflammation in this life-threatening infection. It is possibly a harbinger of a markedly increased risk of mortality in these patients.
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Insuficiência Adrenal , COVID-19 , Humanos , Corticosteroides/efeitos adversos , Insuficiência Adrenal/epidemiologia , Estado Terminal , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Estudos Retrospectivos , Centros de Atenção TerciáriaRESUMO
We have previously demonstrated that acute ingestion of inorganic nitrate (NO3-)-rich beetroot juice (BRJ), a source of nitric oxide (NO) via the NO3- â nitrite (NO2-) â NO pathway, can improve muscle speed and power in older individuals. It is not known, however, whether this effect is maintained or perhaps even enhanced with repeated ingestion, or if tolerance develops as with organic nitrates, e.g., nitroglycerin. Using a double-blind, placebo-controlled, crossover design, we therefore studied 16 community-dwelling older (age 71 ± 5 y) individuals after both acute and short-term (i.e., daily for 2 wk) BRJ supplementation. Blood samples were drawn and blood pressure was measured periodically during each â¼3 h experiment, with muscle function determined using isokinetic dynamometry. Acute ingestion of BRJ containing 18.2 ± 6.2 mmol of NO3- increased plasma NO3- and NO2- concentrations 23 ± 11 and 2.7 ± 2.1-fold over placebo, respectively. This was accompanied by 5 ± 11% and 7 ± 13% increases in maximal knee extensor speed (Vmax) and power (Pmax), respectively. After daily supplementation for 2 wk, BRJ ingestion elevated NO3- and NO2- levels 24 ± 12 and 3.3 ± 4.0-fold, respectively, whereas Vmax and Pmax were 7 ± 9% and 9 ± 11% higher than baseline. No changes were observed in blood pressure or in plasma markers of oxidative stress with either acute or short-term NO3- supplementation. We conclude that both acute and short-term dietary NO3- supplementation result in similar improvements in muscle function in older individuals. The magnitudes of these improvements are sufficient to offset the decline resulting from a decade or more of aging and are therefore likely to be clinically significant.
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Beta vulgaris , Dióxido de Nitrogênio , Masculino , Humanos , Feminino , Idoso , Pressão Sanguínea , Suplementos Nutricionais , Nitratos , Músculo Esquelético/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo , Método Duplo-Cego , Estudos Cross-Over , Sucos de Frutas e VegetaisRESUMO
Older individuals fatigue more rapidly during, and recover more slowly from, dynamic exercise. Women are particularly vulnerable to these deleterious effects of aging, which increases their risk of falling. We have shown that dietary nitrate (NO3 - ), a source of nitric oxide (NO) via the NO3 - â nitrite (NO2 - ) â NO pathway, enhances muscle speed and power in older individuals in the non-fatigued state; however, it is unclear if it reduces fatigability and/or improves recoverability in this population. Using a double-blind, placebo-controlled, crossover design, we studied 18 older (age 70 ± 4 years) women who were administered an acute dose of beetroot juice (BRJ) containing either 15.6 ± 3.6 or <0.05 mmol of NO3 - . Blood samples were drawn throughout each ~3 h visit for plasma NO3 - and NO2 - analysis. Peak torque was measured during, and periodically for 10 min after, 50 maximal knee extensions performed at 3.14 rad/s on an isokinetic dynamometer. Ingestion of NO3 - -containing BRJ increased plasma NO3 - and NO2 - concentrations by 21 ± 8 and 4 ± 4 fold, respectively. However, there were no differences in muscle fatigue or recovery. Dietary NO3 - increases plasma NO3 - and NO2 - concentrations but does not reduce fatigability during or enhance recoverability after high intensity exercise in older women.