Androgen receptor markers do not differ between nonresponders and responders to resistance training-induced muscle hypertrophy.

The aim of this study was to investigate whether baseline values and acute and chronic changes in androgen receptors (AR) markers, including total AR, cytoplasmic (cAR), and nuclear (nAR) fractions, as well as DNA-binding activity (AR-DNA), are involved in muscle hypertrophy responsiveness by comparing young nonresponder and responder individuals. After 10 wk of resistance training (RT), participants were identified as nonresponders using two typical errors (TE) obtained through two muscle cross-sectional area (mCSA) ultrasound measurements (2 × TE; 4.94%), and the highest responders within our sample were numerically matched. Muscle biopsies were performed at baseline, 24 h after the first RT session (acute responses), and 96 h after the last session (chronic responses). AR, cAR, and nAR were analyzed using Western blotting, and AR-DNA was analyzed using an ELISA-oligonucleotide assay. Twelve participants were identified as nonresponders (ΔmCSA: -1.32%) and 12 as responders (ΔmCSA: 21.35%). There were no baseline differences between groups in mCSA, AR, cAR, nAR, or AR-DNA (P > 0.05). For acute responses, there was a significant difference between nonresponders (+19.5%) and responders (-14.4%) in AR-DNA [effect size (ES) = -1.39; 95% confidence interval (CI): -2.53 to -0.16; P = 0.015]. There were no acute between-group differences in any other AR markers (P > 0.05). No significant differences between groups were observed in chronic responses across any AR markers (P > 0.05). Nonresponders and responders presented similar baseline, acute, and chronic results for the majority of the AR markers. Thus, our findings do not support the influence of AR markers on muscle hypertrophy responsiveness to RT in untrained individuals.NEW & NOTEWORTHY We explored, for the first time, the influence of androgen receptor (AR) through the separation of cytoplasmic and nuclear cell fractions [i.e., cytoplasmic androgen receptor (cAR), nuclear androgen receptor (nAR), and androgen receptor DNA-binding activity (AR-DNA)] on muscle hypertrophy responsiveness to resistance training. The absence of muscle hypertrophy in naïve individuals does not seem to be explained by baseline values, and acute or chronic changes in AR markers.

Resistance training-induced changes in muscle proteolysis and extracellular matrix remodeling biomarkers in the untrained and trained states.

PURPOSE: Resistance training (RT) induces muscle growth at varying rates across RT phases, and evidence suggests that the muscle-molecular responses to training bouts become refined or attenuated in the trained state. This study examined how proteolysis-related biomarkers and extracellular matrix (ECM) remodeling factors respond to a bout of RT in the untrained (UT) and trained (T) state. METHODS: Participants (19 women and 19 men) underwent 10 weeks of RT. Biopsies of vastus lateralis were collected before and after (24 h) the first (UT) and last (T) sessions. Vastus lateralis cross-sectional area (CSA) was assessed before and after the experimental period. RESULTS: There were increases in muscle and type II fiber CSAs. In both the UT and T states, calpain activity was upregulated and calpain-1/-2 protein expression was downregulated from Pre to 24 h. Calpain-2 was higher in the T state. Proteasome activity and 20S proteasome protein expression were upregulated from Pre to 24 h in both the UT and T. However, proteasome activity levels were lower in the T state. The expression of poly-ubiquitinated proteins was unchanged. MMP activity was downregulated, and MMP-9 protein expression was elevated from Pre to 24 h in UT and T. Although MMP-14 protein expression was acutely unchanged, this marker was lower in T state. TIMP-1 protein levels were reduced Pre to 24 h in UT and T, while TIMP-2 protein levels were unchanged. CONCLUSION: Our results are the first to show that RT does not attenuate the acute-induced response of proteolysis and ECM remodeling-related biomarkers.

Effects of low-load resistance training with blood flow restriction on muscle fiber myofibrillar and extracellular area.

Blood flow restriction applied during low-load resistance training (LL-BFR) induces a similar increase in the cross-sectional area of muscle fibers (fCSA) compared to traditional high-load resistance training (HL-RT). However, it is unclear whether LL-BFR leads to differential changes in myofibrillar spacing in muscle fibers and/or extracellular area compared to HL-RT. Therefore, this study aimed to investigate whether the hypertrophy of type I and II fibers induced by LL-BFR or HL-RT is accompanied by differential changes in myofibrillar and non-myofibrillar areas. In addition, we examined if extracellular spacing was differentially affected between these two training protocols. Twenty recreationally active participants were assigned to LL-BFR or HL-RT groups and underwent a 6-week training program. Muscle biopsies were taken before and after the training period. The fCSA of type I and II fibers, the area occupied by myofibrillar and non-myofibrillar components, and extracellular spacing were analyzed using immunohistochemistry techniques. Despite the significant increase in type II and mean (type I + II) fCSA (p < 0.05), there were no significant changes in the proportionality of the myofibrillar and non-myofibrillar areas [∼86% and ∼14%, respectively (p > 0.05)], indicating that initial adaptations to LL-BFR are primarily characterized by conventional hypertrophy rather than disproportionate non-myofibrillar expansion. Additionally, extracellular spacing was not significantly altered between protocols. In summary, our study reveals that LL-BFR, like HL-RT, induces skeletal muscle hypertrophy with proportional changes in the areas occupied by myofibrillar, non-myofibrillar, and extracellular components.

Effects of Resistance Training Overload Progression Protocols on Strength and Muscle Mass.

The aim of this study was to compare the effects of progressive overload in resistance training on muscle strength and cross-sectional area (CSA) by specifically comparing the impact of increasing load (LOADprog) versus an increase in repetitions (REPSprog). We used a within-subject experimental design in which 39 previously untrained young persons (20 men and 19 women) had their legs randomized to LOADprog and REPSprog. Outcomes were assessed before and after 10 weeks of training. Muscle strength was assessed using the one repetition maximum (1RM) test on the leg extension exercise, and the CSA of the vastus lateralis was assessed by ultrasonography. Both protocols increased 1RM values from pre (LOADprog: 52.90±16.32 kg; REPSprog: 51.67±15.84 kg) to post (LOADprog: 69.05±18.55 kg, REPSprog: 66.82±17.95 kg), with no difference between them (P+>+0.05). Similarly, both protocols also increased in CSA values from pre (LOADprog: 21.34±4.71 cm²; REPSprog: 21.08±4.62 cm²) to post (LOADprog: 23.53±5.41 cm², REPSprog: 23.39±5.19 cm²), with no difference between them (P+>+0.05). In conclusion, our findings indicate that the progression of overload through load or repetitions can be used to promote gains in strength and muscle hypertrophy in young men and women in the early stages of training.

Comparison of Traditional and Advanced Resistance Training Paradigms on Muscle Hypertrophy in Trained Individuals: A Systematic Review and Meta-Analysis.

Trained individuals may require variations in training stimuli and advanced resistance training paradigms (ADV) to increase skeletal muscle hypertrophy. However, no meta-analysis has examined how ADV versus traditional (TRAD) approaches may differentially affect hypertrophic outcomes in trained populations. The aim of this review was to determine whether the skeletal muscle hypertrophy responses induced by TRAD differed from ADV in resistance-trained individuals. Furthermore, we sought to examine potential effects of dietary factors, participants' training status, and training loads. We searched for peer-reviewed, randomized controlled trials (published in English) conducted in healthy resistance-trained adults performing a period of TRAD and ADV with pre-to-post measurement(s) of muscle hypertrophy in PubMed, Web of Science, SPORTDiscus, and MEDLINE databases up to October 2022. A formal meta-analysis was conducted in Revman5, and risk of bias was assessed by ROB2. Ten studies met the inclusion criteria. Results indicated no difference between ADV and TRAD for muscle thickness (SMD = 0.05, 95% CI: -0.20 0.29, p = 0.70), lean mass (SMD = -0.01, 95% CI: -0.26 0.23, p = 0.92), muscle cross-sectional area (SMD = -0.07, 95% CI: -0.36 0.22, p = 0.64), or all measurements analyzed together (SMD = -0.00, 95% CI: -0.15 0.14, p = 0.95). No heterogeneity or inconsistencies were observed; however, unclear risk of bias was present in most of the studies. Short-term ADV does not induce superior skeletal muscle hypertrophy responses when compared with TRAD in trained individuals. This review was not previously registered.

A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation.

Creatine (Cr) and phosphocreatine (PCr) are physiologically essential molecules for life, given they serve as rapid and localized support of energy- and mechanical-dependent processes. This evolutionary advantage is based on the action of creatine kinase (CK) isozymes that connect places of ATP synthesis with sites of ATP consumption (the CK/PCr system). Supplementation with creatine monohydrate (CrM) can enhance this system, resulting in well-known ergogenic effects and potential health or therapeutic benefits. In spite of our vast knowledge about these molecules, no integrative analysis of molecular mechanisms under a systems biology approach has been performed to date; thus, we aimed to perform for the first time a convergent functional genomics analysis to identify biological regulators mediating the effects of Cr supplementation in health and disease. A total of 35 differentially expressed genes were analyzed. We identified top-ranked pathways and biological processes mediating the effects of Cr supplementation. The impact of CrM on miRNAs merits more research. We also cautiously suggest two dose-response functional pathways (kinase- and ubiquitin-driven) for the regulation of the Cr uptake. Our functional enrichment analysis, the knowledge-based pathway reconstruction, and the identification of hub nodes provide meaningful information for future studies. This work contributes to a better understanding of the well-reported benefits of Cr in sports and its potential in health and disease conditions, although further clinical research is needed to validate the proposed mechanisms.

Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review.

Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na+/Cl--dependent Cr transporter (CRT). Once within cells, creatine kinase (CK) catalyzes the reversible transphosphorylation reaction between [Mg2+:ATP4-]2- and Cr to produce phosphocreatine (PCr) and [Mg2+:ADP3-]-. We aimed to perform a comprehensive and bioinformatics-assisted review of the most recent research findings regarding Cr metabolism. Specifically, several public databases, repositories, and bioinformatics tools were utilized for this endeavor. Topics of biological complexity ranging from structural biology to cellular dynamics were addressed herein. In this sense, we sought to address certain pre-specified questions including: (i) What happens when creatine is transported into cells? (ii) How is the CK/PCr system involved in cellular bioenergetics? (iii) How is the CK/PCr system compartmentalized throughout the cell? (iv) What is the role of creatine amongst different tissues? and (v) What is the basis of creatine transport? Under the cellular allostasis paradigm, the CK/PCr system is physiologically essential for life (cell survival, growth, proliferation, differentiation, and migration/motility) by providing an evolutionary advantage for rapid, local, and temporal support of energy- and mechanical-dependent processes. Thus, we suggest the CK/PCr system acts as a dynamic biosensor based on chemo-mechanical energy transduction, which might explain why dysregulation in Cr metabolism contributes to a wide range of diseases besides the mitigating effect that Cr supplementation may have in some of these disease states.

ZnO:SBA-15 Nanocomposites for Potential Use in Sunscreen: Preparation, Properties, Human Skin Penetration and Toxicity.

AIM: We evaluated the effects of the incorporation of zinc oxide (ZnO) nanoparticles in a mesoporous matrix, aiming to improve the textural, structural and morphological properties and verify their safety so that they can be applied in sunscreen cosmetics. MATERIALS AND METHODS: ZnO nano-particles were incorporated into an ordered mesoporous silica matrix known as Santa Barbara Amorphous-15 (SBA-15), using post-synthesis methodology. The resulting nanocomposites were characterized using X-ray diffraction, small angle X-ray scattering, N2 adsorption-desorption isotherms, Fourier transform infrared spectroscopy, scanning electron microscopy and predicted in vitro sun protector factor (SPF) estimation. Effectiveness and safety were evaluated by antimicrobial activity, in vitro cell toxicity and non-invasive multi-photon tomography with fluorescence lifetime imaging. RESULTS: The structure of the nanocomposites was similar to that of SBA-15, with little perturbation caused by ZnO incorporation. Nanocomposites had an increased in vitro SPF, reduced cytotoxic activity and favourable antimicrobial properties compared to ZnO. ZnO:SBA-15 nanocomposites exhibited no measurable toxicity when applied to human skin in vivo. CONCLUSION: Due to their suitable physicochemical properties and improved safety compared to bare ZnO nanoparticles, the ZnO:SBA-15 nanocomposites show promise for use in cosmetic applications.

Alternative Methods to Animal Studies for the Evaluation of Topical/ Transdermal Drug Delivery Systems.

It is critical to develop an effective understanding of the interaction between the drug, delivery system and skin in order to predict and assess skin penetration and permeation. Experimental models for the assessment of topical and transdermal delivery systems must permit evaluation of these complex interactions. Whilst in the past, animal models were commonly used, recent regulatory guidelines, based on 3R principles (refinement, reduction, replacement), encourage the rational use of animals. Alternative methods have been proposed for use in the development of topical and transdermal delivery systems which are often used in combination. We will review the current state of the art in alternative methods for topical and transdermal delivery systems development, including technologies that can assist in the characterization of skin penetration/permeation studies.

Development and Evaluation of Lipid Nanoparticles Containing Natural Botanical Oil for Sun Protection: Characterization and in vitro and in vivo Human Skin Permeation and Toxicity.

The use of sunscreen products is widely promoted by schools, government agencies, and health-related organizations to minimize sunburn and skin damage. In this study, we developed stable solid lipid nanoparticles (SLNs) containing the chemical UV filter octyl methoxycinnamate (OMC). In parallel, we produced similar stable SLNs in which 20% of the OMC content was replaced by the botanical urucum oil. When these SLNs were applied to the skin of human volunteers, no changes in fluorescence lifetimes or redox ratios of the endogenous skin fluorophores were seen, suggesting that the formulations did not induce toxic responses in the skin. Ex vivo (skin diffusion) tests showed no significant penetration. In vitro studies showed that when 20% of the OMC was replaced by urucum oil, there was no reduction in skin protection factor (SPF), suggesting that a decrease in the amount of chemical filter may be a viable alternative for an effective sunscreen, in combination with an antioxidant-rich vegetable oil, such as urucum. There is a strong trend towards increasing safety of sun protection products through reduction in the use of chemical UV filters. This work supports this approach by producing formulations with lower concentrations of OMC, while maintaining the SPF. Further investigations of SPF in vivo are needed to assess the suitability of these formulations for human use.

From global to regional and back again: common climate stressors of marine ecosystems relevant for adaptation across five ocean warming hotspots.

Ocean warming 'hotspots' are regions characterized by above-average temperature increases over recent years, for which there are significant consequences for both living marine resources and the societies that depend on them. As such, they represent early warning systems for understanding the impacts of marine climate change, and test-beds for developing adaptation options for coping with those impacts. Here, we examine five hotspots off the coasts of eastern Australia, South Africa, Madagascar, India and Brazil. These particular hotspots have underpinned a large international partnership that is working towards improving community adaptation by characterizing, assessing and projecting the likely future of coastal-marine food resources through the provision and sharing of knowledge. To inform this effort, we employ a high-resolution global ocean model forced by Representative Concentration Pathway 8.5 and simulated to year 2099. In addition to the sea surface temperature, we analyse projected stratification, nutrient supply, primary production, anthropogenic CO2 -driven ocean acidification, deoxygenation and ocean circulation. Our simulation finds that the temperature-defined hotspots studied here will continue to experience warming but, with the exception of eastern Australia, may not remain the fastest warming ocean areas over the next century as the strongest warming is projected to occur in the subpolar and polar areas of the Northern Hemisphere. Additionally, we find that recent rapid change in SST is not necessarily an indicator that these areas are also hotspots of the other climatic stressors examined. However, a consistent facet of the hotspots studied here is that they are all strongly influenced by ocean circulation, which has already shown changes in the recent past and is projected to undergo further strong change into the future. In addition to the fast warming, change in local ocean circulation represents a distinct feature of present and future climate change impacting marine ecosystems in these areas.

Categories that should be removed from mental disorders classifications: perspectives and rationales of clinicians from eight countries.

OBJECTIVE: To explore the rationales of mental health professionals (mainly psychiatrists and psychologists) from 8 countries for removing specific diagnostic categories from mental disorders classification systems. METHOD: As part of a larger study, 505 participants indicated which of 60 major disorders should be omitted from mental disorders classification systems and provided rationales. Rationale statements were analyzed using inductive content analysis. RESULTS: The majority of clinicians (60.4%) indicated that 1 or more disorders should be removed. The most common rationales were (a) problematic boundaries between normal and psychopathological conditions (45.9% of total removal recommendations), (b) problematic boundaries among mental disorders (25.4%), and (c) problematic boundaries between mental and physical disorders (24.0%). The categories most frequently recommended for deletion were gender identity disorder, sexual dysfunction, and paraphilias, usually because clinicians viewed these categories as being based on stigmatization of a way of being and behaving. A range of neurocognitive disorders were described as better conceptualized as nonpsychiatric medical conditions. Results were analyzed by country and country income level. Although gender identity disorder was the category most frequently recommended for removal overall, clinicians from Spain, India, and Mexico were most likely to do so and clinicians from Nigeria and Japan least likely, probably because of social and systemic factors that vary by country. Systematic differences in removal rationales by country income level may be related to the development, structure, and functioning of health systems. CONCLUSION: Implications for development and dissemination of the classification of mental and behavioral disorders in WHO's ICD-11 are discussed.

Treating non-retentive encopresis with rewarded scheduled toilet visits.

We evaluated the effects of rewarded scheduled toilet sits on non-retentive encopretic behavior of an elementary-school student receiving services for serious emotional disturbance. A multidisciplinary team implemented the 8-week intervention using a multiple baseline across settings design. The results showed an increase in sitting on the toilet and a decline in encopretic episodes in both school and home settings. These findings support the use of a behavioral intervention for children with significant behavioral disorders within a classroom setting.

Microbial structural diversity estimated by dilution-extinction of phenotypic traits and T-RFLP analysis along a land-use intensification gradient.

The present work tested whether the relationship between functional traits and inoculum density reflected structural diversity in bacterial communities from a land-use intensification gradient applying a mathematical model. Terminal restriction fragment length polymorphism (T-RFLP) analysis was also performed to provide an independent assessment of species richness. Successive 10-fold dilutions of a soil suspension were inoculated onto Biolog GN(R) microplates. Soil bacterial density was determined by total cell and plate counts. The relationship between phenotypic traits and inoculum density fit the model, allowing the estimation of maximal phenotypic potential (Rmax) and inoculum density (KI) at which Rmax will be half-reduced. Though Rmax decreased with time elapsed since clearing of native vegetation, KI remained high in two of the disturbed sites. The genetic pool of bacterial community did not experience a significant reduction, but the active fraction responding in the Biolog assay was adversely affected, suggesting a reduction in the functional potential.