The last decade has seen a dramatic increase in general interest in and research into vitamin D, with many athletes now taking vitamin D supplements as part of their everyday dietary regimen. The ...most recognized role of vitamin D is its regulation of calcium homeostasis; there is a strong relationship between vitamin D and bone health in non-athletic individuals. In contrast, data have consistently failed to demonstrate any relationship between serum 25OHD and bone health, which may in part be due to the osteogenic stimulus of exercise. Vitamin D may interact with extra-skeletal tissues such as muscle and the immune system to modulate recovery from damaging exercise and infection risk. Given that many athletes now engage in supplementation, often consuming extreme doses of vitamin D, it is important to assess whether excessive vitamin D can be detrimental to health. It has been argued that toxic effects only occur when serum 25OHD concentrations are greater than 180 nmol·l
−1
, but data from our laboratory have suggested high-dose supplementation could be problematic. Finally, there is a paradoxical relationship between serum 25OHD concentration, ethnicity, and markers of bone health: Black athletes often present with low serum 25OHD without physiological consequences. One explanation for this could be genetic differences in vitamin D binding protein due to ethnicity, resulting in greater concentrations of bioavailable (or free) vitamin D in some ethnic groups. In the absence of any pathology, screening may be unnecessary and could result in incorrect supplementation. Data must now be re-examined, taking into consideration bioavailable or “free” vitamin D in ethnically diverse groups to enable new thresholds and target concentrations to be established; perhaps, for now, it is time to “set vitamin D free”.
The field of exercise physiology has undergone significant technological advancements since the pioneering works of exercise physiologists in the early to mid‐20th century. Historically, the ability ...to detect metabolites in biofluids from exercising participants was limited to single‐metabolite analyses. However, the rise of metabolomics, a discipline focused on the comprehensive analysis of metabolites within a biological system, has facilitated a more intricate understanding of metabolic pathways and networks in exercise. This review explores some of the pivotal technological and bioinformatic advancements that have propelled metabolomics to the forefront of exercise physiology research. Metabolomics offers a unique ‘fingerprint’ of cellular activity, offering a broader spectrum than traditional single‐metabolite assays. Techniques, including mass spectrometry and nuclear magnetic resonance spectroscopy, have significantly improved the speed and sensitivity of metabolite analysis. Nonetheless, challenges persist, including study design and data interpretation issues. This review aims to serve as a guide for exercise physiologists to facilitate better research design, data analysis and interpretation within metabolomics. The potential of metabolomics in bridging the gap between genotype and phenotype is emphasised, underscoring the critical importance of careful study design and the selection of appropriate metabolomics techniques. Furthermore, the paper highlights the need to deeply understand the broader scientific context to discern meaningful metabolic changes. The emerging field of fluxomics, which seeks to quantify metabolic reaction rates, is also introduced as a promising avenue for future research.
What is the topic of this review?
The integration of metabolomics in exercise physiology.
What advances does it highlight?
Technolgical advances in the study of metabolites, with particular relevance to exercise.
Pathogenic mutations in LAMIN A/C (LMNA) cause abnormal nuclear structure and laminopathies. These diseases have myriad tissue-specific phenotypes, including dilated cardiomyopathy (DCM), but how ...LMNA mutations result in tissue-restricted disease phenotypes remains unclear. We introduced LMNA mutations from individuals with DCM into human induced pluripotent stem cells (hiPSCs) and found that hiPSC-derived cardiomyocytes, in contrast to hepatocytes or adipocytes, exhibit aberrant nuclear morphology and specific disruptions in peripheral chromatin. Disrupted regions were enriched for transcriptionally active genes and regions with lower LAMIN B1 contact frequency. The lamina-chromatin interactions disrupted in mutant cardiomyocytes were enriched for genes associated with non-myocyte lineages and correlated with higher expression of those genes. Myocardium from individuals with LMNA variants similarly showed aberrant expression of non-myocyte pathways. We propose that the lamina network safeguards cellular identity and that pathogenic LMNA variants disrupt peripheral chromatin with specific epigenetic and molecular characteristics, causing misexpression of genes normally expressed in other cell types.
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•Pathogenic LMNA variants disrupt peripheral chromatin in a cell-type-specific manner•Loss of lamina-bound chromatin occurs in regions with specific characteristics•Peripheral chromatin organization maintains silencing of alternative fate genes
Shah et al. demonstrate that pathogenic LMNA variants affect peripheral chromatin organization in a cell-type-specific manner. Their data suggest that lamina-chromatin interactions guard cellular identity. Pathogenic LMNA variants disrupt peripheral chromatin organization and abrogate normal silencing of alternative fate genes in cardiomyocytes.
Exercise-induced muscle damage (EIMD) is characterized by symptoms that present both immediately and for up to 14 days after the initial exercise bout. The main consequence of EIMD for the athlete is ...the loss of skeletal muscle function and soreness. As such, numerous nutrients and functional foods have been examined for their potential to ameliorate the effects of EIMD and accelerate recovery, which is the purpose of many nutritional strategies for the athlete. However, the trade-off between recovery and adaptation is rarely considered. For example, many nutritional interventions described in this review target oxidative stress and inflammation, both thought to contribute to EIMD but are also crucial for the recovery and adaptation process. This calls into question whether long term administration of supplements and functional foods used to target EIMD is indeed best practice. This rapidly growing area of sports nutrition will benefit from careful consideration of the potential hormetic effect of long term use of nutritional aids that ameliorate muscle damage. This review provides a concise overview of what EIMD is, its causes and consequences and critically evaluates potential nutritional strategies to ameliorate EIMD. We present a pragmatic practical summary that can be adopted by practitioners and direct future research, with the purpose of pushing the field to better consider the fine balance between recovery and adaptation and the potential that nutritional interventions have in modulating this balance.
"Sleep Low-Train Low" is a training-nutrition strategy intended to purposefully reduce muscle glycogen availability around specific exercise sessions, potentially amplifying the training stimulus via ...augmented cell signalling. The aim of this study was to assess the feasibility of a 3-week home-based "sleep low-train low" programme and its effects on cycling performance in trained athletes. Fifty-five trained athletes (Functional Threshold Power FTP: 258 ± 52W) completed a home-based cycling training program consisting of evening high-intensity training (6 x 5 min at 105% FTP), followed by low-intensity training (1 hr at 75% FTP) the next morning, three times weekly for three consecutive weeks. Participant's daily carbohydrate (CHO) intake (6 g·kg.sup.-1 ·d.sup.-1) was matched but timed differently to manipulate CHO availability around exercise: no CHO consumption post- HIT until post-LIT sessions Sleep Low (SL), n = 28 or CHO consumption evenly distributed throughout the day Control (CON), n = 27. Sessions were monitored remotely via power data uploaded to an online training platform, with performance tests conducted pre-, post-intervention. LIT exercise intensity reduced by 3% across week 1, 3 and 2% in week 2 (P < 0.01) with elevated RPE in SL vs. CON (P < 0.01). SL enhanced FTP by +5.5% vs. +1.2% in CON (P < 0.01). Comparable increases in 5-min peak power output (PPO) were observed between groups (P < 0.01) with +2.3% and +2.7% in SL and CON, respectively (P = 0.77). SL 1-min PPO was unchanged (+0.8%) whilst CON improved by +3.9% (P = 0.0144). Despite reduced relative training intensity, our data demonstrate short-term "sleep low-train low" intervention improves FTP compared with typically "normal" CHO availability during exercise. Importantly, training was completed unsupervised at home (during the COVID-19 pandemic), thus demonstrating the feasibility of completing a "sleep low-train low" protocol under non-laboratory conditions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The sirtuin gene family (
SIRT) is hypothesized to regulate the aging process and play a role in cellular repair. This work demonstrates that SIRT3
−/− mouse embryonic fibroblasts (MEFs) exhibit ...abnormal mitochondrial physiology as well as increases in stress-induced superoxide levels and genomic instability. Expression of a single oncogene (
Myc or
Ras) in SIRT3
−/− MEFs results in in vitro transformation and altered intracellular metabolism. Superoxide dismutase prevents transformation by a single oncogene in SIRT3
−/− MEFs and reverses the tumor-permissive phenotype as well as stress-induced genomic instability. In addition, SIRT3
−/− mice develop ER/PR-positive mammary tumors. Finally, human breast and other human cancer specimens exhibit reduced
SIRT3 levels. These results identify
SIRT3 as a genomically expressed, mitochondria-localized tumor suppressor.
► SIRT3 is a genomically expressed, mitochondrial-localized in vitro tumor suppressor ► Mice lacking SIRT3 develop ER/PR-positive invasive ductal mammary tumors ► SIRT3 is decreased in human breast cancer tumors and several other malignancies ► SIRT3 loss results in aberrant mitochondrial metabolism and genomic instability
Laminopathies are a clinically heterogeneous group of disorders caused by mutations in the
gene, which encodes the nuclear envelope proteins lamins A and C. The most frequent diseases associated with
...mutations are characterized by skeletal and cardiac involvement, and include autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy type 1B, and
-related congenital muscular dystrophy (
-CMD). Although the exact pathophysiological mechanisms responsible for
-CMD are not yet understood, severe contracture and muscle atrophy suggest that mutations may impair skeletal muscle growth. Using human muscle stem cells (MuSCs) carrying
-CMD mutations, we observe impaired myogenic fusion with disorganized cadherin/β catenin adhesion complexes. We show that skeletal muscle from
-CMD mice is unable to hypertrophy in response to functional overload, due to defective fusion of activated MuSCs, defective protein synthesis and defective remodeling of the neuromuscular junction. Moreover, stretched myotubes and overloaded muscle fibers with
-CMD mutations display aberrant mechanical regulation of the yes-associated protein (YAP). We also observe defects in MuSC activation and YAP signaling in muscle biopsies from
-CMD patients. These phenotypes are not recapitulated in closely related but less severe EDMD models. In conclusion, combining studies in vitro, in vivo, and patient samples, we find that
-CMD mutations interfere with mechanosignaling pathways in skeletal muscle, implicating A-type lamins in the regulation of skeletal muscle growth.
1) To characterize PSQI and ESS scores, and their relationship to each other, in an adult community sample; 2) To determine whether PSQI and ESS scores, in combination with each other, were ...associated with distinct demographic, clinical, and sleep characteristics.
The PSQI, ESS, clinical rating scales, sleep diaries, actigraphy, and home polysomnography were collected from 187 community-dwelling adults (mean age 59.5 years, 47.1% women, 41.2% African Americans) as part of a study investigating novel cardiovascular risk factors. Correlations, cluster analysis, principal components analysis, MANOVA, ANOVA, and regressions were used to characterize the relationships between the PSQI, ESS, and other study variables
Mean PSQI score was 6.3 (3.4), and mean ESS score was 8.2 (3.9). PSQI and ESS correlated weakly with each other (r = 0.16, p = 0.03), but segregated from each other on principal components analysis. Groups of participants categorized by either cluster analysis of PSQI and ESS scores, or by scores above or below traditional cut-off values, differed from each other on psychological/stress symptoms and quantitative and qualitative sleep diary measures, but not on actigraphic or polysomnographic measures. Specifically, higher PSQI scores were associated with female sex, greater psychological distress, and greater sleep disturbance on sleep diaries.
The PSQI and ESS measure orthogonal dimensions of sleep-wake symptoms, but neither is related to objective sleep measures. The PSQI is more closely related to psychological symptom ratings and sleep diary measures than the ESS. These instruments are not likely to be useful as screening measures for polysomnographic sleep abnormalities.
Patient-Reported Outcomes in Orthopaedics Christensen, Daniel L; Dickens, Jonathan F; Freedman, Brett ...
Journal of bone and joint surgery. American volume,
2018-March-7, Letnik:
100, Številka:
5
Journal Article
Recenzirano
Odprti dostop
➤ Patient-reported outcomes (PROs) assess a patient’s perspective of health, function, and quality of life associated with health conditions and medical interventions.
➤ Health-care value is the ...ratio of health outcomes achieved relative to the total cost of care for a medical condition.
➤ Common PRO designs assess general quality of life, system or region-specific conditions, disease-specific conditions, or mixed outcome measure designs.
➤ Patient-Reported Outcomes Measurement Information System (PROMIS) measures domains of health (e.g., fatigue, physical function, and depressive symptoms), not disease or injury-specific outcomes, allowing for comparability across conditions and normative scoring.
➤ PROs offer a unique format to the clinician for understanding the impact of medical conditions or interventions and, as a result, may improve the care provided.
Abstract We present a strong lensing analysis of COOL J1241+2219, the brightest known gravitationally lensed galaxy at z ≥ 5, based on new multiband Hubble Space Telescope (HST) imaging data. The ...lensed galaxy has a redshift of z = 5.043, placing it shortly after the end of the “Epoch of Reionization,” and an AB magnitude z AB = 20.47 mag (Khullar et al.). As such, it serves as a touchstone for future research of that epoch. The high spatial resolution of HST reveals internal structure in the giant arc, from which we identify 15 constraints and construct a robust lens model. We use the lens model to extract the cluster mass and lensing magnification. We find that the mass enclosed within the Einstein radius of the z = 1.001 cluster lens is M ( < 5 .″ 77 ) = 1.079 − 0.007 + 0.023 × 10 13 M ☉ , significantly lower than other known strong lensing clusters at its redshift. The average magnification of the giant arc is 〈 μ arc 〉 = 76 − 20 + 40 , a factor of 2.4 − 0.7 + 1.4 greater than previously estimated from ground-based data; the flux-weighted average magnification is 〈 μ arc 〉 = 92 − 31 + 37 . We update the current measurements of the stellar mass and star formation rate (SFR) of the source for the revised magnification to log ( M ⋆ / M ⊙ ) = 9.7 ± 0.3 and SFR = 10.3 − 4.4 + 7.0 M ⊙ yr −1 , respectively. The powerful lensing magnification acting upon COOL J1241+2219 resolves the source and enables future studies of the properties of its star formation on a clump-by-clump basis. The lensing analysis presented here will support upcoming multiwavelength characterization with HST and JWST data of the stellar mass assembly and physical properties of this high-redshift lensed galaxy.
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