Chronic granulomatous disease (CGD) is an inherited immunodeficiency due to defective leukocyte NADPH responsible for recurrent infections and aberrant inflammation. Mutations in the CYBB gene are responsible for the X-linked CGD and account for approximately 70% of the cases. CGD is diagnosed during childhood in males. Female carriers may have biased X-inactivation and may present with clinical manifestations depending on the level of residual NADPH oxidase activity. We report the case of a previously asymptomatic female carrier who was diagnosed at age 67 with a skin infection with the rare fungus Paecilomyces lilacinus as the first manifestation of CGD. Dihydrorhodamine 123 (DHR) activity was below 10%. Next-generation sequencing (NGS) revealed mutations in DNMT3A, ASXL1, and STAG2 suggesting that clonal hematopoiesis could be responsible for a progressive loss of NADPH oxidase activity and the late onset of X-linked CGD in this patient. Long-term follow-up of asymptomatic carrier women seems to be essential after 50 years old.
Objective: To examine (i) the associations between physical activity dimensions, cardiorespiratory fitness and body composition and, (ii) the associations between physical activity dimensions, cardiorespiratory fitness, body composition and biomarkers of cardiometabolic health in persons with spinal cord injury (SCI).
Methods: A cross-sectional prospective cohort study with 7-day follow-up was conducted. Body composition, cardiorespiratory fitness and biomarkers of cardiometabolic health were measured in thirty-three participants with SCI (> 1 year post injury). Physical activity dimensions were objectively assessed over 7-days.
Results: Activity energy expenditure (r =.43), physical activity level (r =.39), and moderate-to-vigorous physical activity (MVPA) (r =.48) were significantly (P < 0.001) associated with absolute (L/min) peak oxygen uptake (?O2 peak). ?O2 peak was significantly higher in persons performing ≥150 MVPA minutes/week compared to <40 minutes/week (P?=?0.003). Individual physical activity dimensions were not significantly associated with biomarkers of cardiometabolic health. However, body composition characteristics (BMI, waist and hip circumference) showed significant (P < 0.04), moderate (r >.30) associations with parameters of metabolic regulation, lipid profiles and inflammatory biomarkers. Relative ?O2 peak (ml/kg/min) was moderately associated with only insulin sensitivity (r?=?0.37, P?=?0.03).
Conclusions: Physical activity dimensions are associated with cardiorespiratory fitness; however, stronger and more consistent associations suggest that poor cardiometabolic health is associated with higher body fat content. Given these findings, the regulation of energy balance should be an important consideration for researchers and clinicians looking to improve cardiometabolic health in persons with SCI. 相似文献
Major depressive disorder (MDD) is a prevalent condition in older adults. Although antidepressant drugs are commonly prescribed, efficacy is variable, and older patients are more prone to side effects. Repetitive transcranial magnetic stimulation (rTMS) is an alternative therapy used increasingly in the treatment of MDD. Even though recent studies have shown efficacy of rTMS in elderly depressed patients, the safety and efficacy of accelerated rTMS has not been studied in this population.
Methods
Data were retrospectively analyzed for adults with treatment-resistant depression (N?=?73, n?=?19 ≥60years, n?=?54 <60 years) who underwent an accelerated protocol of 30 sessions (2 sessions per day) of left dorsolateral prefrontal cortex high-frequency (20 Hz) rTMS.
Results
There were statistically significant improvements in depression and anxiety symptoms from baseline to post-treatment in both age groups, but those 60years and older showed statistically greater improvement in depression and anxiety symptom scores (p?=?0.01) than those less than 60. There were significantly more responders (p?=?0.001) and remitters (p?=?0.023) in the older group. The age groups did not differ significantly in clinical and demographic characteristics or severity of current depressive episode, although baseline anxiety was less severe in those 60years and older. Unipolar and bipolar patients had a similar clinical response, and treatment appeared to be well tolerated by all patients.
Conclusion
Our results suggest that accelerated rTMS protocol is a safe and effective treatment for unipolar and bipolar depressed subjects, including older adults. 相似文献
Skeletal muscle aging is associated with a progressive decline in muscle mass and strength, a process termed sarcopenia. Evidence suggests that accumulation of mitochondrial dysfunction plays a causal role in sarcopenia, which could be triggered by impaired mitophagy. Mitochondrial function, mitophagy and mitochondrial morphology are interconnected aspects of mitochondrial biology, and may coordinately be altered with aging. However, mitochondrial morphology has remained challenging to characterize in muscle, and whether sarcopenia is associated with abnormal mitochondrial morphology remains unknown. Therefore, we assessed the morphology of SubSarcolemmal (SS) and InterMyoFibrillar (IMF) mitochondria in skeletal muscle of young (8-12wk-old) and old (88-96wk-old) mice using a quantitative 2-dimensional transmission electron microscopy approach. We show that sarcopenia is associated with larger and less circular SS mitochondria. Likewise, aged IMF mitochondria were longer and more branched, suggesting increased fusion and/or decreased fission. Accordingly, although no difference in the content of proteins regulating mitochondrial dynamics (Mfn1, Mfn2, Opa1 and Drp1) was observed, a mitochondrial fusion index (Mfn2-to-Drp1 ratio) was significantly increased in aged muscles. Our results reveal that sarcopenia is associated with complex changes in mitochondrial morphology that could interfere with mitochondrial function and mitophagy, and thus contribute to aging-related accumulation of mitochondrial dysfunction and sarcopenia. 相似文献
This study reveals that the entry into World War I in 1917 indexed the decisive transition to the modern period in American political consciousness, ushering in new objects of political discourse, a more rapid pace of change of those objects, and a fundamental reframing of the main tasks of governance. We develop a strategy for identifying meaningful categories in textual corpora that span long historic durées, where terms, concepts, and language use changes. Our approach is able to account for the fluidity of discursive categories over time, and to analyze their continuity by identifying the discursive stream as the object of interest.When did modern political discourse emerge in the United States? What is distinctive of basic understandings of the tasks of governance today, in contrast to those that organized the politics of an earlier period? Can the origins of contemporary political understandings be located in the discourse of the past? The annual State of the Union address (hereafter, SoU), in which the US president reports broadly on the progress and challenges of his administration, provides a singular standpoint from which to address the evolution of the tasks of governance. It can thus be used to investigate old questions like those above using network-based text analysis strategies.This study reveals that the entry into World War I (WWI) in 1917 indexed the decisive transition to the modern period in American political consciousness, ushering in new objects of political discourse, a more rapid pace of change of those objects, and a fundamental reframing of the main tasks of governance. At the same time, this study demonstrates that discourse distinctive to modern politics, although it later crystalized around the liberal welfare state, in fact emerged before the transition to the modern period.We offer a unique view of American political history, which tracks the articulation of the major tasks of governance in American political and social discourse. To do so, we develop a strategy for identifying meaningful categories in textual corpora that span long historic durées. We are able to account for the fluidity of discursive categories over time, and to analyze their continuity by identifying the discursive stream as the object of interest. The methodological approach developed in this article can be used to meaningfully analyze texts produced over very long historical periods, where terms, concepts, and language use changes—to our knowledge, a problem not satisfactorily solved. 相似文献