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\"An easy-to-start, simple-to-maintain, scientifically sound, and eminently usable twelve-week program of small steps on the road to better health Small Changes, Big Results is not about cutting all the carbohydrates out of your diet. Or replacing every single gram of sugar with omega-3 fatty acids. It's not about doing one hundred sit-ups a day, or getting on the treadmill whenever you have a free second. In fact, it's not about any of the total lifestyle-replacement gimmicks--whether diet, exercise, or pop psychology--that have swept our culture in recent years, putting untold millions of Americans on the risky roller coaster of success and failure that defines fad diets and programs. Not here. Small Changes, Big Results is about reality--the reality of what you can do, the reality of what you want to do, and the reality of what works. It's about introducing a series of small changes each week for three months in the three core areas of diet and nutrition; exercise and fitness; and emotional wellness. For each of the twelve weeks, nutritionist Ellie Krieger introduces a very finite, completely practical action plan for the week--and not only are these tasks incredibly doable, they're in fact so accessible that it's tough not to be inspired. For example, in Week 1 the nutrition task is merely to go shopping, buy some healthful pantry items, and start keeping track of what you eat; the exercise consists of taking three twenty-minute walks; and the wellness aspect is to do a five-minute breathing exercise. That's it. And it doesn't really get any harder. But these small changes do in fact lead to big results. At the end of twelve weeks, a totally unhealthy diet has been overhauled: armed with easy, delicious recipes and tips, you've removed unhelpful munchies and replaced them with healthful snacking, you've cut down on lethal trans fats while adding beneficial fat choices, you've replaced refined grains with whole grains, you're eating more fish and less red meat, and so forth. Yet you've never been forbidden to eat a single thing: instead of prohibiting entire food groups, Ellie categorizes foods as Usually, Sometimes, and Rarely--and now you should be eating more from the Usually choices, less from the Rarely category. Furthermore, you've integrated physical activity into your life, and you've developed a set of tools to help you deal with stress--you're not only eating better, but you're also exercising better and feeling better. The beauty of this program is that none of these action steps is remotely intimidating, because they're not a full immersion into a totally new lifestyle. Instead, it's a series of incremental changes--removing bad habits one by one, while at the same time adding good ones. There's nothing to scare you off--on the contrary, here's a whole book full of small changes that produce big results. From the Hardcover edition\"-- Provided by publisher.

Background A number of resistance training (RT) program variables can be manipulated to maximize muscular hypertrophy. One variable of primary interest in this regard is RT frequency. Frequency can refer to the number of resistance training sessions performed in a given period of time, as well as to the number of times a specific muscle group is trained over a given period of time. Objective We conducted a systematic review and meta-analysis to determine the effects of resistance training frequency on hypertrophic outcomes. Methods Studies were deemed eligible for inclusion if they met the following criteria: (1) were an experimental trial published in an English-language refereed journal; (2) directly compared different weekly resistance training frequencies in traditional dynamic exercise using coupled concentric and eccentric actions; (3) measured morphologic changes via biopsy, imaging, circumference, and/or densitometry; (4) had a minimum duration of 4 weeks; and (5) used human participants without chronic disease or injury. A total of ten studies were identified that investigated RT frequency in accordance with the criteria outlined. Results Analysis using binary frequency as a predictor variable revealed a significant impact of training frequency on hypertrophy effect size ( P  = 0.002), with higher frequency being associated with a greater effect size than lower frequency (0.49 ± 0.08 vs. 0.30 ± 0.07, respectively). Statistical analyses of studies investigating training session frequency when groups are matched for frequency of training per muscle group could not be carried out and reliable estimates could not be generated due to inadequate sample size. Conclusions When comparing studies that investigated training muscle groups between 1 to 3 days per week on a volume-equated basis, the current body of evidence indicates that frequencies of training twice a week promote superior hypertrophic outcomes to once a week. It can therefore be inferred that the major muscle groups should be trained at least twice a week to maximize muscle growth; whether training a muscle group three times per week is superior to a twice-per-week protocol remains to be determined.

Recent studies have drawn attention to the evolution of protein dynamics, in addition to sequence and structure, based on the premise structure-encodes-dynamics-encodes-function. Of interest is to understand how functional differentiation is accomplished while maintaining the fold, or how intrinsic dynamics plays out in the evolution of structural variations and functional specificity. We performed a systematic computational analysis of 26,899 proteins belonging to 116 CATH superfamilies. Characterizing cooperative mechanisms and convergent/divergent features that underlie the shared/differentiated dynamics of family members required a methodology that lends itself to efficient analyses of large ensembles of proteins. We therefore introduced, SignDy, an integrated pipeline for evaluating the signature dynamics of families based on elastic network models. Our analysis confirmed that family members share conserved, highly cooperative (global) modes of motion. Importantly, our analysis discloses a subset of motions that sharply distinguishes subfamilies, which lie in a low-to-intermediate frequency regime of the mode spectrum. This regime has maximal impact on functional differentiation of families into subfamilies, while being evolutionarily conserved among subfamily members. Notably, the high-frequency end of the spectrum also reveals evolutionary conserved features across and within subfamilies; but in sharp contrast to global motions, high-frequency modes are minimally collective. Modulation of robust/conserved global dynamics by low-to-intermediate frequency fluctuations thus emerges as a versatile mechanism ensuring the adaptability of selected folds and the specificity of their subfamilies. SignDy further allows for dynamics-based categorization as a new layer of information relevant to distinctive mechanisms of action of subfamilies, beyond sequence or structural classifications.

Background Current recommendations on resistance training (RT) frequency for gains in muscular strength are based on extrapolations from limited evidence on the topic, and thus their practical applicability remains questionable. Objective To elucidate this issue, we conducted a systematic review and meta-analysis of the studies that compared muscular strength outcomes with different RT frequencies. Methods To carry out this review, English-language literature searches of the PubMed/MEDLINE, Scopus, and SPORTDiscus databases were conducted. The meta-analysis was performed using a random-effects model. The meta-analysis models were generated with RT frequencies classified as a categorical variable as either 1, 2, 3, or 4+ times/week, or, if there were insufficient data in subgroup analyses, the training frequencies were categorized as 1, 2, or 3 times/week. Subgroup analyses were performed for potential moderators, including (1) training volume; (2) exercise selection for the 1 repetition maximum (RM) test (for both multi-joint and single-joint exercises); (3) upper and lower body strength gains; (4) training to muscular failure (for studies involving and not involving training to muscular failure); (5) age (for both middle-aged/older adults and young adults); and (6) sex (for men and for women). The methodological quality of studies was appraised using the modified Downs and Black checklist. Results A total of 22 studies were found to meet the inclusion criteria. The average score on the Downs and Black checklist was 18 (range 13–22 points). Four studies were classified as being of good methodological quality, while the rest were classified as being of moderate methodological quality. Results of the meta-analysis showed a significant effect ( p  = 0.003) of RT frequency on muscular strength gains. Effect sizes increased in magnitude from 0.74, 0.82, 0.93, and 1.08 for training 1, 2, 3, and 4+ times per week, respectively. A subgroup analysis of volume-equated studies showed no significant effect ( p  = 0.421) of RT frequency on muscular strength gains. The subgroup analysis for exercise selection for the 1RM test suggested a significant effect of RT frequency on multi-joint ( p  < 0.001), but not single-joint, 1RM test results ( p  = 0.324). The subgroup analysis for upper and lower body showed a significant effect of frequency ( p  = 0.004) for upper body, but not lower body, strength gains ( p  = 0.070). In the subgroup analysis for studies in which the training was and was not carried out to muscular failure, no significant effect of RT frequency was found. The subgroup analysis for the age groups suggested a significant effect of training frequency among young adults ( p  = 0.024), but not among middle-aged and older adults ( p  = 0.093). Finally, the subgroup analysis for sex indicated a significant effect of RT frequency on strength gains in women ( p  = 0.030), but not men ( p  = 0.190). Conclusions The results of the present systematic review and meta-analysis suggest a significant effect of RT frequency as higher training frequencies are translated into greater muscular strength gains. However, these effects seem to be primarily driven by training volume because when the volume is equated, there was no significant effect of RT frequency on muscular strength gains. Thus, from a practical standpoint, greater training frequencies can be used for additional RT volume, which is then likely to result in greater muscular strength gains. However, it remains unclear whether RT frequency on its own has significant effects on strength gain. It seems that higher RT frequencies result in greater gains in muscular strength on multi-joint exercises in the upper body and in women, and, finally, in contrast to older adults, young individuals seem to respond more positively to greater RT frequencies. More evidence among resistance-trained individuals is needed as most of the current studies were performed in untrained participants.

Krieger, JW. Single vs. multiple sets of resistance exercise for muscle hypertrophya meta-analysis. J Strength Cond Res 24(4)1150-1159, 2010-Previous meta-analyses have compared the effects of single to multiple sets on strength, but analyses on muscle hypertrophy are lacking. The purpose of this study was to use multilevel meta-regression to compare the effects of single and multiple sets per exercise on muscle hypertrophy. The analysis comprised 55 effect sizes (ESs), nested within 19 treatment groups and 8 studies. Multiple sets were associated with a larger ES than a single set (difference = 0.10 ± 0.04; confidence interval [CI]0.02, 0.19; p = 0.016). In a dose-response model, there was a trend for 2-3 sets per exercise to be associated with a greater ES than 1 set (difference = 0.09 ± 0.05; CI−0.02, 0.20; p = 0.09), and a trend for 4-6 sets per exercise to be associated with a greater ES than 1 set (difference = 0.20 ± 0.11; CI−0.04, 0.43; p = 0.096). Both of these trends were significant when considering permutation test p values (p < 0.01). There was no significant difference between 2-3 sets per exercise and 4-6 sets per exercise (difference = 0.10 ± 0.10; CI−0.09, 0.30; p = 0.29). There was a tendency for increasing ESs for an increasing number of sets (0.24 for 1 set, 0.34 for 2-3 sets, and 0.44 for 4-6 sets). Sensitivity analysis revealed no highly influential studies that affected the magnitude of the observed differences, but one study did slightly influence the level of significance and CI width. No evidence of publication bias was observed. In conclusion, multiple sets are associated with 40% greater hypertrophy-related ESs than 1 set, in both trained and untrained subjects.

ObjectiveWe performed a systematic review, meta-analysis and meta-regression to determine if dietary protein supplementation augments resistance exercise training (RET)-induced gains in muscle mass and strength.Data sourcesA systematic search of Medline, Embase, CINAHL and SportDiscus.Eligibility criteriaOnly randomised controlled trials with RET ≥6 weeks in duration and dietary protein supplementation.DesignRandom-effects meta-analyses and meta-regressions with four a priori determined covariates. Two-phase break point analysis was used to determine the relationship between total protein intake and changes in fat-free mass (FFM).ResultsData from 49 studies with 1863 participants showed that dietary protein supplementation significantly (all p<0.05) increased changes (means (95% CI)) in: strength—one-repetition-maximum (2.49 kg (0.64, 4.33)), FFM (0.30 kg (0.09, 0.52)) and muscle size—muscle fibre cross-sectional area (CSA; 310 µm2 (51, 570)) and mid-femur CSA (7.2 mm2 (0.20, 14.30)) during periods of prolonged RET. The impact of protein supplementation on gains in FFM was reduced with increasing age (−0.01 kg (−0.02,–0.00), p=0.002) and was more effective in resistance-trained individuals (0.75 kg (0.09, 1.40), p=0.03). Protein supplementation beyond total protein intakes of 1.62 g/kg/day resulted in no further RET-induced gains in FFM.Summary/conclusionDietary protein supplementation significantly enhanced changes in muscle strength and size during prolonged RET in healthy adults. Increasing age reduces and training experience increases the efficacy of protein supplementation during RET. With protein supplementation, protein intakes at amounts greater than ~1.6 g/kg/day do not further contribute RET-induced gains in FFM.

AMPA glutamate receptors (AMPARs), the primary mediators of excitatory neurotransmission in the brain, are either GluA2 subunit-containing and thus Ca 2+ -impermeable, or GluA2-lacking and Ca 2+ -permeable 1 . Despite their prominent expression throughout interneurons and glia, their role in long-term potentiation and their involvement in a range of neuropathologies 2 , structural information for GluA2-lacking receptors is currently absent. Here we determine and characterize cryo-electron microscopy structures of the GluA1 homotetramer, fully occupied with TARPγ3 auxiliary subunits (GluA1/γ3). The gating core of both resting and open-state GluA1/γ3 closely resembles GluA2-containing receptors. However, the sequence-diverse N-terminal domains (NTDs) give rise to a highly mobile assembly, enabling domain swapping and subunit re-alignments in the ligand-binding domain tier that are pronounced in desensitized states. These transitions underlie the unique kinetic properties of GluA1. A GluA2 mutant (F231A) increasing NTD dynamics phenocopies this behaviour, and exhibits reduced synaptic responses, reflecting the anchoring function of the AMPAR NTD at the synapse. Together, this work underscores how the subunit-diverse NTDs determine subunit arrangement, gating properties and ultimately synaptic signalling efficiency among AMPAR subtypes. Calcium-permeable GluA1 AMPA glutamate receptors are structurally and functionally distinct from the prototypical GluA2-containing AMPA receptors, impacting their role in signal transmission, synaptic plasticity and learning.

Background Maximizing the hypertrophic response to resistance training (RT) is thought to be best achieved by proper manipulation of exercise program variables including exercise selection, exercise order, length of rest intervals, intensity of maximal load, and training volume. An often overlooked variable that also may impact muscle growth is repetition duration. Duration amounts to the sum total of the concentric, eccentric, and isometric components of a repetition, and is predicated on the tempo at which the repetition is performed. Objective We conducted a systematic review and meta-analysis to determine whether alterations in repetition duration can amplify the hypertrophic response to RT. Methods Studies were deemed eligible for inclusion if they met the following criteria: (1) were an experimental trial published in an English-language refereed journal; (2) directly compared different training tempos in dynamic exercise using both concentric and eccentric repetitions; (3) measured morphologic changes via biopsy, imaging, and/or densitometry; (4) had a minimum duration of 6 weeks; (5) carried out training to muscle failure, defined as the inability to complete another concentric repetition while maintaining proper form; and (6) used human subjects who did not have a chronic disease or injury. A total of eight studies were identified that investigated repetition duration in accordance with the criteria outlined. Results Results indicate that hypertrophic outcomes are similar when training with repetition durations ranging from 0.5 to 8 s. Conclusions From a practical standpoint it would seem that a fairly wide range of repetition durations can be employed if the primary goal is to maximize muscle growth. Findings suggest that training at volitionally very slow durations (>10s per repetition) is inferior from a hypertrophy standpoint, although a lack of controlled studies on the topic makes it difficult to draw definitive conclusions.

Krieger, JW. Single versus multiple sets of resistance exercisea meta-regression. J Strength Cond Res 23(6)1890-1901, 2009-There has been considerable debate over the optimal number of sets per exercise to improve musculoskeletal strength during a resistance exercise program. The purpose of this study was to use hierarchical, random-effects meta-regression to compare the effects of single and multiple sets per exercise on dynamic strength. English-language studies comparing single with multiple sets per exercise, while controlling for other variables, were considered eligible for inclusion. The analysis comprised 92 effect sizes (ESs) nested within 30 treatment groups and 14 studies. Multiple sets were associated with a larger ES than a single set (difference = 0.26 ± 0.05; confidence interval [CI]0.15, 0.37; p < 0.0001). In a dose-response model, 2 to 3 sets per exercise were associated with a significantly greater ES than 1 set (difference = 0.25 ± 0.06; CI0.14, 0.37; p = 0.0001). There was no significant difference between 1 set per exercise and 4 to 6 sets per exercise (difference = 0.35 ± 0.25; CI−0.05, 0.74; p = 0.17) or between 2 to 3 sets per exercise and 4 to 6 sets per exercise (difference = 0.09 ± 0.20; CI−0.31, 0.50; p = 0.64). There were no interactions between set volume and training program duration, subject training status, or whether the upper or lower body was trained. Sensitivity analysis revealed no highly influential studies, and no evidence of publication bias was observed. In conclusion, 2 to 3 sets per exercise are associated with 46% greater strength gains than 1 set, in both trained and untrained subjects.

AMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission at excitatory synapses in the brain. Glutamate binding to the receptor’s ligand-binding domains (LBDs) leads to ion channel activation and desensitization. Gating kinetics shape synaptic transmission and are strongly modulated by transmembrane AMPAR regulatory proteins (TARPs) through currently incompletely resolved mechanisms. Here, electron cryo-microscopy structures of the GluA1/2 TARP-γ8 complex, in both open and desensitized states (at 3.5 Å), reveal state-selective engagement of the LBDs by the large TARP-γ8 loop (‘β1’), elucidating how this TARP stabilizes specific gating states. We further show how TARPs alter channel rectification, by interacting with the pore helix of the selectivity filter. Lastly, we reveal that the Q/R-editing site couples the channel constriction at the filter entrance to the gate, and forms the major cation binding site in the conduction path. Our results provide a mechanistic framework of how TARPs modulate AMPAR gating and conductance. AMPA glutamate receptors, mediate the majority of excitatory signaling in the brain. Here the authors show how the auxiliary subunit TARP-γ8 shapes gating kinetics, ion conductance and rectification properties of the heteromeric GluA1/2 AMPA receptor.