Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data ...analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.
Abstract
This review provides the reader with current insights on testicular adrenal rest tumors (TARTs), a complication in male patients with congenital adrenal hyperplasia (CAH). In recent studies, ...an overall TART prevalence of 40% (range, 14% to 89%) in classic patients with CAH is found. Reported differences are mainly caused by the method of detection and the selected patient population. Biochemically, histologically, and molecularly, TARTs exhibit particular adrenal characteristics and were therefore thought to originate from aberrant adrenal cells. More recently, TARTs have been found to also exhibit testicular characteristics. This has led to the hypothesis of pluripotent cells as the origin of TARTs. High concentrations of ACTH could cause hyperplasia of these pluripotent cells, as TARTs appear to be associated with poor hormonal control with concomitant elevated ACTH. Unfortunately, as yet there are no methods to prevent the development of TARTs, nor are there guidelines to treat patients with TARTs. Intensified glucocorticoid treatment could improve fertility status in some cases, although studies report contradicting results. TARTs can also lead to irreversible testicular damage, and therefore semen cryopreservation could be offered to patients with TARTs. Further research should focus on the etiology and pharmacological treatment to prevent TART development or to treat TARTs and improve the fertility status of patients with TARTs.
Schoenfeld, BJ, Pope, ZK, Benik, FM, Hester, GM, Sellers, J, Nooner, JL, Schnaiter, JA, Bond-Williams, KE, Carter, AS, Ross, CL, Just, BL, Henselmans, M, and Krieger, JW. Longer interset rest periods ...enhance muscle strength and hypertrophy in resistance-trained men. J Strength Cond Res 30(7): 1805-1812, 2016-The purpose of this study was to investigate the effects of short rest intervals normally associated with hypertrophy-type training versus long rest intervals traditionally used in strength-type training on muscular adaptations in a cohort of young, experienced lifters. Twenty-one young resistance-trained men were randomly assigned to either a group that performed a resistance training (RT) program with 1-minute rest intervals (SHORT) or a group that employed 3-minute rest intervals (LONG). All other RT variables were held constant. The study period lasted 8 weeks with subjects performing 3 total body workouts a week comprised 3 sets of 8-12 repetition maximum (RM) of 7 different exercises per session. Testing was performed prestudy and poststudy for muscle strength (1RM bench press and back squat), muscle endurance (50% 1RM bench press to failure), and muscle thickness of the elbow flexors, triceps brachii, and quadriceps femoris by ultrasound imaging. Maximal strength was significantly greater for both 1RM squat and bench press for LONG compared to SHORT. Muscle thickness was significantly greater for LONG compared to SHORT in the anterior thigh, and a trend for greater increases was noted in the triceps brachii (p = 0.06) as well. Both groups saw significant increases in local upper body muscle endurance with no significant differences noted between groups. This study provides evidence that longer rest periods promote greater increases in muscle strength and hypertrophy in young resistance-trained men.
RE-1 silencing transcription factor (REST) (known also as NRSF) is a well-known transcription repressor whose strong decrease induces the distinction of neurons with respect to the other cells. Such ...distinction depends on the marked increased/decreased expression of specific genes, accompanied by parallel changes of the corresponding proteins. Many properties of REST had been identified in the past. Here we report those identified during the last 5 years. Among physiological discoveries are hundreds of genes governed directly/indirectly by REST, the mechanisms of its neuron/fibroblast conversions, and the cooperations with numerous distinct factors induced at the epigenetic level and essential for REST specific functions. New effects induced in neurons during brain diseases depend on the localization of REST, in the nucleus, where functions and toxicity occur, and in the cytoplasm. The effects of REST, including cell aggression or protection, are variable in neurodegenerative diseases in view of the distinct mechanisms of their pathology. Moreover, cooperations are among the mechanisms that govern the severity of brain cancers, glioblastomas, and medulloblastomas. Interestingly, the role in cancers is relevant also for therapeutic perspectives affecting the REST cooperations. In conclusion, part of the new REST knowledge in physiology and pathology appears promising for future developments in research and brain diseases.
Objective
To examine rest–activity circadian rhythm (RAR) and cognitive decline in older men.
Design
Longitudinal.
Setting
Osteoporotic Fractures in Men (MrOS) and ancillary Outcomes of Sleep ...Disorders in Men (MrOS Sleep) studies.
Participants
MrOS and MrOS Sleep participants (N=2,754; mean age 76.0 ± 5.3).
Measurements
The Modified Mini‐Mental State examination (3MS) was used to assess cognition at baseline (2003–05) and follow‐up examinations (2005–06 and 2007–09). Wrist actigraphy was used to measure 24‐hour activity counts at baseline. RAR variables included amplitude (strength of activity rhythm), mesor (mean activity level), pseudo F‐statistic (overall circadian rhythm robustness), and acrophase (time of daily peak activity).
Results
After an average of 3.4 ± 0.5 years, men with lower amplitudes, mesors, and pseudo F‐statistics had greater decline in 3MS performance (amplitude: –0.7 points Q1 vs –0.5 points Q4, p<.001; mesor: –0.5 points Q1 vs –0.2 points Q4, p=.01; pseudo F‐statistic: –0.5 points Q1 vs –0.3 points Q4, p<.001). Lower amplitudes and pseudo‐F statistics were associated with greater odds of clinically significant cognitive decline (≥5‐point decrease) (amplitude Q1 vs. Q4: odds ratio (OR)=1.4, 95% confidence interval (CI)=1.0–1.9; pseudo‐F statistic Q1 vs Q4: OR=1.4, 95% CI=1.0–1.9). Men with phase‐advanced acrophase had greater odds of clinically significant cognitive decline (OR=1.8, 95% CI=1.2–2.8). Results were adjusted for multiple confounders.
Conclusion
Several parameters of disrupted RAR (lower amplitude, pseudo F‐statistic, mesor, phase‐advanced acrophase) were associated with greater cognitive decline in older community‐dwelling men. These findings contribute to a growing body of evidence suggesting that altered RARs are associated with cognitive decline in older adults. J Am Geriatr Soc 66:2136–2143, 2018.
Summary
In the last three decades the two‐process model of sleep regulation has served as a major conceptual framework in sleep research. It has been applied widely in studies on fatigue and ...performance and to dissect individual differences in sleep regulation. The model posits that a homeostatic process (Process S) interacts with a process controlled by the circadian pacemaker (Process C), with time‐courses derived from physiological and behavioural variables. The model simulates successfully the timing and intensity of sleep in diverse experimental protocols. Electrophysiological recordings from the suprachiasmatic nuclei (SCN) suggest that S and C interact continuously. Oscillators outside the SCN that are linked to energy metabolism are evident in SCN‐lesioned arrhythmic animals subjected to restricted feeding or methamphetamine administration, as well as in human subjects during internal desynchronization. In intact animals these peripheral oscillators may dissociate from the central pacemaker rhythm. A sleep/fast and wake/feed phase segregate antagonistic anabolic and catabolic metabolic processes in peripheral tissues. A deficiency of Process S was proposed to account for both depressive sleep disturbances and the antidepressant effect of sleep deprivation. The model supported the development of novel non‐pharmacological treatment paradigms in psychiatry, based on manipulating circadian phase, sleep and light exposure. In conclusion, the model remains conceptually useful for promoting the integration of sleep and circadian rhythm research. Sleep appears to have not only a short‐term, use‐dependent function; it also serves to enforce rest and fasting, thereby supporting the optimization of metabolic processes at the appropriate phase of the 24‐h cycle.
Tufano, JJ, Brown, LE, and Haff, GG. Theoretical and practical aspects of different cluster set structures: a systematic review. J Strength Cond Res 31(3): 848-867, 2017-When performing a set of ...successive repetitions, fatigue ensues and the quality of performance during subsequent repetitions contained in the set decreases. Oftentimes, this response may be beneficial because fatigue may stimulate the neuromuscular system to adapt, resulting in a super-compensatory response. However, there are instances in which accumulated fatigue may be detrimental to training or performance adaptations (i.e., power development). In these instances, the ability to recover and maintain repetition performance would be considered essential. By providing intermittent rest between individual repetitions or groups of repetitions within a set, an athlete is able to acutely alleviate fatigue, allowing performance to remain relatively constant throughout an exercise session. Within the scientific literature, a set that includes intermittent rest between individual repetitions or groups of repetitions within a set is defined as a cluster set. Recently, cluster sets (CS) have received more attention as researchers have begun to examine the acute and chronic responses to this relatively novel set structure. However, much of the rest period terminology within the literature lacks uniformity and many authors attempt to compare largely different protocols with the same terminology. Additionally, the present body of scientific literature has mainly focused on the effects of CS on power output, leaving the effects of CS on strength and hypertrophy relatively unexplored. Therefore, the purpose of this review was to further delineate cluster set terminology, describe the acute and chronic responses of CS, and explain the need for further investigation of the effects of CS.
Testicular adrenal rest tumors (TART) are a common complication in males with classic 21-hydroxylase deficiency (21OHD). TART are likely to contribute to the androgen excess in 21OHD patients, but a ...direct quantification of steroidogenesis from these tumors has not been yet done.
We aimed to define the production of 11-oxygenated 19-carbon (11oxC19) steroids by TART.
Using liquid chromatography-tandem mass spectrometry, steroids were measured in left (n = 7) and right (n = 4) spermatic vein and simultaneously drawn peripheral blood (n = 7) samples from 7 men with 21OHD and TART. For comparison, we also measured the peripheral steroid concentrations in 5 adrenalectomized patients and 12 age- and BMI-matched controls. Additionally, steroids were quantified in TART cell- and adrenal cell-conditioned medium, with and without adrenocorticotropic hormone (ACTH) stimulation.
Compared with peripheral blood from 21OHD patients with TART, the spermatic vein samples displayed the highest gradient for 11β-hydroxytestosterone (11OHT; 96-fold) of the 11oxC19 steroids, followed by 11-ketotestosterone (47-fold) and 11β-hydroxyandrostenedione (11OHA4; 29-fold), suggesting production of these steroids in TART. TART cells produced higher levels of testosterone and lower levels of A4 and 11OHA4 after ACTH stimulation compared with adrenal cells, indicating ACTH-induced production of testosterone in TART.
In patients with 21OHD, TART produce 11oxC19 steroids, but in different proportions than the adrenals. The very high ratio of 11OHT in spermatic vs peripheral vein blood suggests the 11-hydroxylation of testosterone by TART, and the in vitro results indicate that this metabolism is ACTH-sensitive.
Adrenocortical hyperplasia and adrenal rest tumor (ART) formation are common in congenital adrenal hyperplasia (CAH). Although driven by excessive corticotropin, much is unknown regarding the ...morphology and transformation of these tissues. Our study objective was to characterize CAH-affected adrenals and ART and compare with control adrenal and gonadal tissues.
CAH adrenals, ART and control tissues were analyzed by histology, immunohistochemistry, and transcriptome sequencing. We investigated protein expression of the ACTH receptor (MC2R), steroidogenic (CYP11B2, CYP11B1, CYB5A) and immune (CD20, CD3, CD68) biomarkers, and delta-like 1 homolog (DLK1), a membrane bound protein broadly expressed in fetal and many endocrine cells. RNA was isolated and gene expression was analyzed by RNA sequencing (RNA-seq) followed by principle component, and unsupervised clustering analyses.
Based on immunohistochemistry, CAH adrenals and ART demonstrated increased zona reticularis (ZR)-like CYB5A expression, compared to CYP11B1, and CYP11B2, markers of zona fasciculata and zona glomerulosa respectively. CYP11B2 was mostly absent in CAH adrenals and absent in ART. DLK1 was present in CAH adrenal, ART, and also control adrenal and testis, but was absent in control ovary. Increased expression of adrenocortical marker MC2R, was observed in CAH adrenals compared to control adrenal. Unlike control tissues, significant nodular lymphocytic infiltration was observed in CAH adrenals and ART, with CD20 (B-cell), CD3 (T-cell) and CD68 (macrophage/monocyte) markers of inflammation. RNA-seq data revealed co-expression of adrenal
, and testis-specific
in testicular ART indicating the presence of both gonadal and adrenal features, and high expression of DLK1 in ART, CAH adrenals and control adrenal. Principal component analysis indicated that the ART transcriptome was more similar to CAH adrenals and least similar to control testis tissue.
CAH-affected adrenal glands and ART have similar expression profiles and morphology, demonstrating increased CYB5A with ZR characteristics and lymphocytic infiltration, suggesting a common origin that is similarly affected by the abnormal hormonal milieu. Immune system modulators may play a role in tumor formation of CAH.
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