Prolonged periods of skeletal muscle inactivity or mechanical unloading (bed rest, hindlimb unloading, immobilization, spaceflight and reduced step) can result in a significant loss of musculoskeletal mass, size and strength which ultimately lead to muscle atrophy. With advancement in understanding of the molecular and cellular mechanisms involved in disuse skeletal muscle atrophy, several different signaling pathways have been studied to understand their regulatory role in this process. However, substantial gaps exist in our understanding of the regulatory mechanisms involved, as well as their functional significance. This review aims to update the current state of knowledge and the underlying cellular mechanisms related to skeletal muscle loss during a variety of unloading conditions, both in humans and animals. Recent advancements in understanding of cellular and molecular mechanisms, including IGF1-Akt-mTOR, MuRF1/MAFbx, FOXO, and potential triggers of disuse atrophy, such as calcium overload and ROS overproduction, as well as their role in skeletal muscle protein adaptation to disuse is emphasized. We have also elaborated potential therapeutic countermeasures that have shown promising results in preventing and restoring disuse-induced muscle loss. Finally, identified are the key challenges in this field as well as some future prospectives.

This review presents lower body negative pressure (LBNP) as a unique tool to investigate the physiology of integrated systemic compensatory responses to altered hemodynamic patterns during conditions of central hypovolemia in humans. An early review published in Physiological Reviews over 40 yr ago (Wolthuis et al. Physiol Rev 54: 566–595, 1974) focused on the use of LBNP as a tool to study effects of central hypovolemia, while more than a decade ago a review appeared that focused on LBNP as a model of hemorrhagic shock (Cooke et al. J Appl Physiol (1985) 96: 1249–1261, 2004). Since then there has been a great deal of new research that has applied LBNP to investigate complex physiological responses to a variety of challenges including orthostasis, hemorrhage, and other important stressors seen in humans such as microgravity encountered during spaceflight. The LBNP stimulus has provided novel insights into the physiology underlying areas such as intolerance to reduced central blood volume, sex differences concerning blood pressure regulation, autonomic dysfunctions, adaptations to exercise training, and effects of space flight. Furthermore, approaching cardiovascular assessment using prediction models for orthostatic capacity in healthy populations, derived from LBNP tolerance protocols, has provided important insights into the mechanisms of orthostatic hypotension and central hypovolemia, especially in some patient populations as well as in healthy subjects. This review also presents a concise discussion of mathematical modeling regarding compensatory responses induced by LBNP. Given the diverse applications of LBNP, it is to be expected that new and innovative applications of LBNP will be developed to explore the complex physiological mechanisms that underline health and disease.

Introduction The Metabolic Syndrome (MetS) describes the clustering of cardio-metabolic risk factors—including abdominal obesity, insulin resistance, elevated blood pressure, high levels of triglycerides, and low levels of high-density lipoproteins—that increase the risk for developing cardiovascular diseases and type 2 diabetes mellitus. However, a generally accepted definition of MetS in pediatric patients is still lacking. Objectives The aim was to summarize current prevalence data of childhood MetS as well as to discuss the continuing disagreement between different pediatric definitions and the clinical importance of such diagnosis. Methodology A systematic literature search on the prevalence of pediatric MetS was conducted. Articles that were published during the past 5 years (2014–2019), using at least one of four predetermined classifications (International Diabetes Federation, Cook et al., Ford et al., and de Ferranti et al.), were included. Results The search resulted in 1167 articles, of which 31 publications met all inclusion criteria. Discussion The prevalence of MetS ranged between 0.3 and 26.4%, whereby the rising number of children and adolescents with MetS partly depended on the definition used. The IDF definition generally provided the lowest prevalences (0.3–9.5%), whereas the classification of de Ferranti et al. yielded the highest (4.0–26.4%). In order to develop a more valid definition, further research on long-term consequences of childhood risk factors such as abdominal obesity, insulin resistance, hypertension, and dyslipidemia is needed. There is also a temptation to suggest one valid, globally accepted definition of metabolic syndrome for pediatric populations but we believe that it is more appropriate to suggest definitions of MetS that are specific to males vs. females, as well as being specific to race/ethnicity or geographic region. Finally, while this notion of definitions of MetS specific to certain subgroups is important, it still needs to be tested in future research.

Background and Purpose-We investigated cerebral blood flow regulation in astronauts before and after flights. We hypothesized that autoregulation would be different before flight and after flight between nonfinishers and the finishers of a stand test. Methods-Twenty-seven astronauts from shuttle missions lasting 8 to 16 days underwent a 10-minute stand test: 10 days before flight, 1 to 2 hours and 3 days after landing. Mean blood flow velocity of the middle cerebral artery (MCA) was measured using transcranial Doppler; Mean arterial pressure was measured using a Finapres (Ohmeda, Englewood, CO) and was adjusted to the level of the MCA (BP MCA ). Cross-spectral power, gain, phase, and coherence were determined for the relation between BP MCA and the cerebrovascular resistance index mean blood flow velocity/BP MCA . Results-BP MCA was reduced with stand (PϽ0.001). Differences between finishers and nonfinishers (Pϭ0.011) and over test days (Pϭ0.004) were observed. Cerebrovascular conductance was affected by stand (PϽ0.001), by group (PϽ0.001) with a group by stand, and test day interaction (PϽ0.01). Preflight data suggest that the nonfinishers were operating at a higher cerebral vasodilation than finishers for a given BP MCA , and on landing day the nonfinishers had a greater decrease in mean blood flow velocity as a function of BP MCA with standing compared to finishers and preflight. There was a significant interaction effect of gender over the test days and from supine to stand (Pϭ0.035). Conclusions-Our results indicate that the cause of presyncope in astronauts may be related to a mismatch of cerebral blood flow with blood pressure. Astronaut gender may also play a role in susceptibility to orthostatic intolerance after flight. (Stroke. 2011;42:1844-1850.)Key Words: cerebral blood flow Ⅲ cerebral hemodynamics Ⅲ microgravity Ⅲ gender Ⅲ transcranial Doppler A fter space flight, there is a wide range of susceptibility to orthostatic intolerance. It is possible that cerebral autoregulation, which ensures that cerebrovascular conductance is changed to maintain a relatively constant level of perfusion in case of fluctuations in blood pressure, 1 could be compromised by the effects of weightlessness.Investigation of cerebral autoregulation after head-down bed rest (HDBR) studies has revealed conflicting results. After 4 days of HDBR, Arbeille et al 2 found no change in dynamic cerebral regulation during head-up tilt. Conversely, Zhang et al 3 found an earlier and greater decline in cerebral blood flow during lower body negative pressure after HDBR and speculated that impairment of cerebral autoregulation may contribute to orthostatic intolerance after bed rest. Pavy Le-Trao 4 showed no major impairment of cerebral autoregulation with HDBR; however, there was a slower response in vasodilation to a sudden decline in blood pressure in participants who had orthostatic intolerance. In the only reported study of astronauts, Iwasaki et al 5 reported improved cerebral autoregulation on landing day; however, all 6 astronauts ...