Variations in strength-speed-power performance across the season: do true changes occur in elite rugby players?

This study aimed to determine, through the use of a highly sensitive statistical tool, whether real changes in performance were present; and compare the rates of meaningful variations in strength, speed, and power parameters at different time-points during the competitive season in national team rugby players. Thirty-two players were assessed 5 times across the season using the following tests: squat jump and countermovement jump tests; 30-m sprint velocity; and one-repetition maximum (1RM) in the half-squat and bench-press exercises. A repeated-measures analysis of variance was conducted to test for differences between successive time-points. Individual coefficients of variation values were used to set target scores for post-measurements and examine whether changes in performance parameters were greater than the natural test variance, thus providing an indication of whether "true changes" occurred. No significant changes were detected in the vertical jump height, 1RM measures, and sprint velocity and momentum throughout the 11-month period (P > 0.05). True changes occurred much more frequently for strength-power measures than for sprint velocity and momentum. Elite rugby union players did not exhibit significant variations in neuromuscular performance across the competitive period, when a group-based analysis was conducted. However, at the individual level, "true changes" in strength-power-(but not in speed-) related qualities were consistently observed over the competitive season.

Diminazene aceturate inhibits the SARS-CoV-2 spike protein-induced inflammation involving leukocyte migration and DNA extracellular traps formation.

AIMS: To investigate the SARS-CoV-2 Spike protein (Spk)-induced inflammatory response and its downmodulation by diminazene aceturate (DIZE). MATERIALS AND METHODS: Through inducing Spk inflammation in murine models, leukocyte migration to the peritoneum, levels of myeloperoxidase (MPO), malondialdehyde (MDA), rolling and adhesion of mesenteric leukocytes, and vascular permeability were investigated. Extracellular DNA traps (DETs) induced by Spk and the production of IL-6 and TNF-α were analyzed using human neutrophils, monocytes, and macrophages. In silico assays assessed the molecular interaction between DIZE and molecules related to leukocyte migration and DETs induction. KEY FINDINGS: Spk triggered acute inflammation, demonstrated by increasing leukocyte migration. Oxidative stress was evidenced by elevated levels of MPO and MDA in the peritoneal liquid. DIZE attenuated cell migration, rolling, and leukocyte adhesion, improved vascular barrier function, mitigated DETs, and reduced the production of Spk-induced pro-inflammatory cytokines. Computational studies supported our findings, showing the molecular interaction of DIZE with targets such as ß2 integrin, PI3K, and PAD2 due to its intermolecular coupling. SIGNIFICANCE: Our results outline a novel role of DIZE as a potential therapeutic agent for mitigating Spk-induced inflammation.

Identifying Critical Evidence Gaps in Wound Closure and Incision Management After Total Knee Arthroplasty: Delphi Panel Insights.

INTRODUCTION: In orthopaedic surgery, particularly total knee arthroplasty (TKA), the management of surgical wounds is critical for optimal wound healing and successful patient outcomes. Despite advances in surgical techniques, challenges persist in effectively managing surgical wounds to prevent complications and infections. This study aimed to identify and address the critical evidence gaps in wound management in TKA, including preoperative optimization, intraoperative options, and for the avoidance of postoperative complications. These are important issues surrounding wound management, which is essential for improving patient recovery and the overall success of the surgery. METHODS: Utilizing the Delphi method, this study brought together 20 experienced orthopaedic surgeons from Europe and North America. Conducted from April to September 2023, the process involved three stages: an initial electronic survey, a virtual meeting, and a concluding electronic survey. The panel reviewed and reached a consensus on 26 specific statements about wound management in TKA based on a comprehensive literature review. During these three stages and after further panel review, an alternative goal of the Delphi panel was to also identify critical evidence gaps in the current understanding of wound management practices for TKA. RESULTS: While the panel reached consensus on various wound management practices, they highlighted several major evidence gaps. Also, there was general consensus on issues such as wound closure methods including the use of mesh-adhesive dressings, skin glue, staples, sutures (including barbed sutures),and negative-pressure wound therapy (NPWT). However, it was deemed necessary that further evidence needs to be generated to address the cost-effectiveness of each and develop best practices for promoting patient outcomes. The identification of these gaps points to areas requiring more in-depth research and improvements to enhance wound care in TKA. DISCUSSION: The identification of these major evidence gaps underscores the need for targeted research in wound management surrounding TKA. Addressing these evidence gaps is crucial for the future development of more effective, efficient, and patient-friendly wound care strategies. Future research should prioritize these areas, focusing on comparative effectiveness studies and further developing clear guidelines for the use of emerging technologies. Bridging these gaps has the potential to improve patient outcomes, reduce complications, and elevate the overall success rate of TKA surgeries.

Relative Acceleration and Maximum Velocity in Rugby Players According to Age Category and Playing Position.

ABSTRACT: Zabaloy, S, Freitas, TT, Alcaraz, PE, Gálvez-González, J, Pereira, LA, Comyns, T, Loturco, I, and Healy, R. Relative acceleration and maximum velocity in rugby players according to age category and playing position. J Strength Cond Res XX(X): 000-000, 2024-This study aimed to: (a) assess the intrasession reliability of the acceleration time constant (i.e., τ) and τ-derived measures; (b) analyze the influence of τ and maximum velocity (Vmax) on 40-m sprint performance and to compare various sprint-related outcomes among rugby players from different playing positions and age categories; and (c) explore the associations between τ and several sprint performance metrics. A total of 300 male rugby players volunteered to participate in this study and were divided into age categories (i.e., under-14 [U14]: n = 91, age: 12.6 ± 0.5 years; under-16 [U16]: n = 85, age: 14.8 ± 0.5 years; under-18 [U18]: n = 75, age: 16.6 ± 0.5 years; and Seniors: n = 49, age: 24.2 ± 4.1 years). The results demonstrated good to excellent reliability for all measured parameters (intraclass correlation coefficient >0.75 and coefficient of variation <9.0%). Younger players (i.e., U14 and U16) displayed lower τ values (effect size: moderate to large; p < 0.02) compared with their older peers (i.e., U18 and Seniors), regardless of their playing position. Moreover, τ was associated with sprint performance metrics at varying levels of correlations (Rho: small to almost perfect; p < 0.001). In conclusion, younger players exhibited lower τ values than their older counterparts, irrespective of their playing positions. The model employed in this study demonstrated its accuracy in assessing several key sprint performance metrics, offering insights that can enhance sprint training programs for rugby players, which can be based on the associations observed among these different variables.

Structure-guided drug design targeting Abl kinase: how structure and regulation can assist in designing new drugs.

The human protein Abelson kinase (Abl), a tyrosine kinase, plays a pivotal role in developing chronic myeloid leukemia (CML). Abl's involvement in various signaling pathways underscores its significance in regulating fundamental biological processes, including DNA damage responses, actin polymerization, and chromatin structural changes. The discovery of the Bcr-Abl oncoprotein, resulting from a chromosomal translocation in CML patients, revolutionized the understanding and treatment of the disease. The introduction of targeted therapies, starting with interferon-alpha and culminating in the development of tyrosine kinase inhibitors (TKIs) like imatinib, significantly improved patient outcomes. However, challenges such as drug resistance and side effects persist, indicating the necessity of research into novel therapeutic strategies. This review describes advancements in Abl kinase inhibitor development, emphasizing rational compound design from structural and regulatory information. Strategies, including bivalent inhibitors, PROTACs, and compounds targeting regulatory domains, promise to overcome resistance and minimize side effects. Additionally, leveraging the intricate structure and interactions of Bcr-Abl may provide insights into developing inhibitors for other kinases. Overall, this review highlights the importance of continued research into Abl kinase inhibition and its broader implications for therapeutic interventions targeting kinase-driven diseases. It provides valuable insights and strategies that may guide the development of next-generation therapies.

Immunomethylomic profiles of long-term head and neck squamous cell carcinoma survivors on immune checkpoint inhibitors.

Aim: This study addresses the challenge of predicting the response of head and neck squamous cell carcinoma (HNSCC) patients to immunotherapy. Methods: Using DNA methylation cytometry, we analyzed the immune profiles of six HNSCC patients who showed a positive response to immunotherapy over a year without disease progression. Results: There was an initial increase in CD8 T memory cells and natural killer cells during the first four cycles of immunotherapy, which then returned to baseline levels after a year. Baseline CD8 T cell levels were lower in HNSCC immunotherapy responders but became similar to those in healthy subjects after immunotherapy. Conclusion: These findings suggest that monitoring fluctuations in immune profiles could potentially identify biomarkers for immunotherapy response in HNSCC patients.

[Box: see text].

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction.

We describe the use of bismuth(III) triflate as an efficient and environmentally friendly catalyst for the Nazarov reaction of aryl vinyl ketones, leading to the synthesis of 3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones. By changing the temperature and reaction time, it was possible to modulate the reactivity, allowing the synthesis of two distinct product classes (3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones) in good to excellent yield. The reaction did not require additives and was insensitive to both air and moisture. Preliminary biological evaluation of some indanones showed a promising profile against some human cancer line cells.

Unsaturation in the air spaces of leaves and its implications.

Modern plant physiological theory stipulates that the resistance to water movement from plants to the atmosphere is overwhelmingly dominated by stomata. This conception necessitates a corollary assumption-that the air spaces in leaves must be nearly saturated with water vapour; that is, with a relative humidity that does not decline materially below unity. As this idea became progressively engrained in scientific discourse and textbooks over the last century, observations inconsistent with this corollary assumption were occasionally reported. Yet, evidence of unsaturation gained little traction, with acceptance of the prevailing framework motivated by three considerations: (1) leaf water potentials measured by either thermocouple psychrometry or the Scholander pressure chamber are largely consistent with the framework; (2) being able to assume near saturation of intercellular air spaces was transformational to leaf gas exchange analysis; and (3) there has been no obvious mechanism to explain a variable, liquid-phase resistance in the leaf mesophyll. Here, we review the evidence that refutes the assumption of universal, near saturation of air spaces in leaves. Refining the prevailing paradigm with respect to this assumption provides opportunities for identifying and developing mechanisms for increased plant productivity in the face of increasing evaporative demand imposed by global climate change.

A first step towards understanding thermomechanical behavior of the Nb-Cr system through interatomic potential development and molecular dynamics simulations.

Utilizing a preliminary interatomic potential, this work represents an initial exploration into the thermomechanical behavior of NbCr solid solutions. Specifically, it examines the effect of different amounts of Cr solute, for which information in the literature is limited. The employed interatomic potential was developed according to the embedded atom model (EAM), and was trained on data derived from density functional theory calculations. While the potential demonstrated reasonable accuracy and predictive power when tested, various results highlight deficiencies and encourage further development and training. Mechanical strength, heat capacities, thermal expansion coefficients, and thermal conductivities were found to decrease with Cr content. Elastic coefficients, too, were observed to be strongly dependent on Cr composition. The Pugh embrittlement criterion was not satisfied for any of the compositions and temperatures explored. Gibbs free energy calculations performed on C14, C15, and C36 NbCr 2 allotropes predicted the C36 structure to be the most thermodynamically favorable across all investigated temperatures and it was found that C36 becomes increasingly more stable relative to the other two phases with increased pressure. The inability of this work to accurately capture the stability of the different Laves phases is most likely due to the shortcomings in the developed potential.

Anticonvulsant and anxiolytic-like potential of the essential oil from the Ocimum basilicum Linn leaves and its major constituent estragole on adult zebrafish (Danio rerio).

The Ocimum species present active compounds with the potential to develop drugs for treating chronic disease conditions, such as anxiety and seizures. The present study aims to investigate the anticonvulsant and anxiolytic-like effect of the essential oil from O. basilicum Linn (OEFOb) leaves and its major constituent estragole (ES) in vivo on adult zebrafish (aZF) and in silico. The aZF were treated with OEFOb or ES or vehicle and submitted to the tests of toxicity, open-field, anxiety, and convulsion and validated the interactions of the estragole on the involvement of GABAergic and serotonergic receptors by molecular docking assay. The results showed that the oral administration of OEFOb and ES did not have a toxic effect on the aZF and showed anxiolytic-like effects with the involvement of GABAA, 5-HT1, 5-HT2A/2C and 5-HT3A/3B as well on anxiety induced by alcohol withdrawal. The OEFOb and ES showed anticonvulsant potential attenuating the seizures induced by pentylenetetrazole (PTZ) by modulation of the GABAA system. Both anxiolytic and anticonvulsant effects were corroborated by the potential of the interaction of ES by in silico assay. These study samples demonstrate the pharmacological evidence and potential for using these compounds to develop new anxiolytic and anticonvulsant drugs.

Effects of Different Conditioning Activities on the Sprint Performance of Elite Sprinters: A Systematic Review With Meta-Analysis.

PURPOSE: Postactivation performance enhancement (PAPE), which refers to the phenomena associated with the attainment of enhanced performance in sport-specific tasks after a conditioning activity, is an important objective of warming-up practices in many sports. This is even more relevant for sprinters, as potential increases in sprinting speed will directly influence their competitive results. This systematic review with meta-analysis evaluated the effects of different PAPE protocols (ie, using plyometrics, strength-power exercises, and resisted/assisted sprints) on the sprinting performance (ie, sprint time or sprint speed) of competitive sprinters. METHODS: Initially, 1205 records published until last December 18 were identified, using the following databases: PubMed/MEDLINE, Scopus, and Clarivate Web of Science. After removing duplicates and screening titles and abstracts, 14 high-quality studies met the inclusion criteria for the meta-analysis. RESULTS: Overall, there were no significant changes in sprint performance after implementing various types of conditioning activities (standardized mean difference [SMD] = 0.16 [95% CI, -0.02 to 0.33]; Z = 1.78; P = .08; I2 = 0%). In addition, when comparing prechanges and postchanges between experimental, control, and other conditions, no significant differences were found in sprint speed or time across all studies (SMD = 0.09 [95% CI, -0.10 to 0.28]; Z = 0.92; P = .36; I = 0%). CONCLUSIONS: Results revealed that different types of conditioning activities may not be capable of acutely enhancing the sprint speed of competitive sprinters. This aligns with previous observations indicating that sprinting is a highly stable physical capacity, a phenomenon that is even more consistent among elite sprinters. Coaches and sport scientists should collaborate to develop more efficient PAPE protocols for these highly specialized athletes, with special attention to study design and individualization, while considering their effects on acceleration versus top speed.

Filamin protects myofibrils from contractile damage through changes in its mechanosensory region.

Filamins are mechanosensitive actin crosslinking proteins that organize the actin cytoskeleton in a variety of shapes and tissues. In muscles, filamin crosslinks actin filaments from opposing sarcomeres, the smallest contractile units of muscles. This happens at the Z-disc, the actin-organizing center of sarcomeres. In flies and vertebrates, filamin mutations lead to fragile muscles that appear ruptured, suggesting filamin helps counteract muscle rupturing during muscle contractions by providing elastic support and/or through signaling. An elastic region at the C-terminus of filamin is called the mechanosensitive region and has been proposed to sense and counteract contractile damage. Here we use molecularly defined mutants and microscopy analysis of the Drosophila indirect flight muscles to investigate the molecular details by which filamin provides cohesion to the Z-disc. We made novel filamin mutations affecting the C-terminal region to interrogate the mechanosensitive region and detected three Z-disc phenotypes: dissociation of actin filaments, Z-disc rupture, and Z-disc enlargement. We tested a constitutively closed filamin mutant, which prevents the elastic changes in the mechanosensitive region and results in ruptured Z-discs, and a constitutively open mutant which has the opposite elastic effect on the mechanosensitive region and gives rise to enlarged Z-discs. Finally, we show that muscle contraction is required for Z-disc rupture. We propose that filamin senses myofibril damage by elastic changes in its mechanosensory region, stabilizes the Z-disc, and counteracts contractile damage at the Z-disc.

Local variation in stress response of juvenile anadromous brown trout, Salmo trutta.

Habitat fragmentation may cut off anadromous salmonids from parts of their potential native habitat and separate previously connected populations. Understanding the consequences of this is vital for fish management and prioritization of restoration activities. Here, we show that there is a significant difference in the body morphology, physiological stress response, and aspects contributing to aerobic capacity between juvenile anadromous brown trout, Salmo trutta, collected at a downstream site and an upstream site, separated by 2 km and several challenging stream sections, in a small unfragmented stream system in western Sweden. Following a standardized stress test, there were significant differences between fish from the upstream and downstream sites (plasma cortisol concentration, plasma osmolality, hematocrit, hemoglobin concentration, and mean corpuscular hemoglobin concentration). Plasma glucose concentration did not significantly differ between fish from the two sites. Fish from the upstream site had larger spleen mass, although there was no evidence of differences in ventricle mass or proportion of compact ventricular myocardium. These physiological differences indicate local variation in stress response and highlight the importance of considering local trait variation in river management. If a section of the river becomes fragmented or degraded, and there are differences in the juveniles in different parts of the river, the consequence for the population might be larger than the proportional loss of habitat.

Major Psychiatric Disorders, Substance Use Behaviors, and Longevity.

Importance: Observational studies suggest that major psychiatric disorders and substance use behaviors reduce longevity, making it difficult to disentangle their relationships with aging-related outcomes. Objective: To evaluate the associations between the genetic liabilities for major psychiatric disorders, substance use behaviors (smoking and alcohol consumption), and longevity. Design, Settings, and Participants: This 2-sample mendelian randomization (MR) study assessed associations between psychiatric disorders, substance use behaviors, and longevity using single-variable and multivariable models. Multiomics analyses were performed elucidating transcriptomic underpinnings of the MR associations and identifying potential proteomic therapeutic targets. This study sourced summary-level genome-wide association study (GWAS) data, gene expression, and proteomic data from cohorts of European ancestry. Analyses were performed from May 2022 to November 2023. Exposures: Genetic susceptibility for major depression (n = 500 199), bipolar disorder (n = 413 466), schizophrenia (n = 127 906), problematic alcohol use (n = 435 563), weekly alcohol consumption (n = 666 978), and lifetime smoking index (n = 462 690). Main Outcomes and Measures: The main outcome encompassed aspects of health span, lifespan, and exceptional longevity. Additional outcomes were epigenetic age acceleration (EAA) clocks. Results: Findings from multivariable MR models simultaneously assessing psychiatric disorders and substance use behaviorsm suggest a negative association between smoking and longevity in cohorts of European ancestry (n = 709 709; 431 503 [60.8%] female; ß, -0.33; 95% CI, -0.38 to -0.28; P = 4.59 × 10-34) and with increased EAA (n = 34 449; 18 017 [52.3%] female; eg, PhenoAge: ß, 1.76; 95% CI, 0.72 to 2.79; P = 8.83 × 10-4). Transcriptomic imputation and colocalization identified 249 genes associated with smoking, including 36 novel genes not captured by the original smoking GWAS. Enriched pathways included chromatin remodeling and telomere assembly and maintenance. The transcriptome-wide signature of smoking was inversely associated with longevity, and estimates of individual smoking-associated genes, eg, XRCC3 and PRMT6, aligned with the smoking-longevity MR analyses, suggesting underlying transcriptomic mediators. Cis-instrument MR prioritized brain proteins associated with smoking behavior, including LY6H (ß, 0.02; 95% CI, 0.01 to 0.03; P = 2.37 × 10-6) and RIT2 (ß, 0.02; 95% CI, 0.01 to 0.03; P = 1.05 × 10-5), which had favorable adverse-effect profiles across 367 traits evaluated in phenome-wide MR. Conclusions: The findings suggest that the genetic liability of smoking, but not of psychiatric disorders, is associated with longevity. Transcriptomic associations offer insights into smoking-related pathways, and identified proteomic targets may inform therapeutic development for smoking cessation strategies.

Follow up care for adults with diabetes treated for severe hypoglycemia by emergency medical Services, 2013-2019.

AIMS: To capture the types and content of healthcare encounters following severe hypoglycemia requiring emergency medical services (EMS) and to correlate their features with subsequent risk of severe hypoglycemia. METHODS: A retrospective cohort was obtained by linking data from a multi-state health system and an advanced life support ambulance service. This identified 1977 EMS calls by 1028 adults with diabetes experiencing hypoglycemia between 1/1/2013-12/31/2019. We evaluated the healthcare engagement over the following 7 days to identify rates of discussion of hypoglycemia, change of diabetes medications, glucagon prescribing, and referral for diabetes. RESULTS: Rates of hypoglycemia discussion increased with escalating levels of care, from 11.5 % after EMS calls without emergency department (ED) transport or outpatient clinical encounters to 98 % among hospitalized patients with outpatient follow-up. EMS transport and outpatient follow-up were associated with significantly higher odds of discussion of hypoglycemia (OR 60 and OR 22.1, respectively). Interventions were not impacted by previous severe hypoglycemia within 30 days. Prescription of glucagon was rare among all patients. CONCLUSIONS: Interventions to prevent recurrent hypoglycemia increase with escalating levels of care but remain inadequate and inconsistent with clinical guidelines. Greater attention is needed to ensure timely diabetes-related follow-up and treatment modification for patients experiencing severe hypoglycemia.

Design of a Lead-Like Cysteine-Targeting Covalent Library and the Identification of Hits to Cys55 of Bfl-1.

Covalent hit identification is a viable approach to identify chemical starting points against difficult-to-drug targets. While most researchers screen libraries of <2k electrophilic fragments, focusing on lead-like compounds can be advantageous in terms of finding hits with improved affinity and with a better chance of identifying cryptic pockets. However, due to the increased molecular complexity, larger numbers of compounds (>10k) are desirable to ensure adequate coverage of chemical space. Herein, the approach taken to build a library of 12k covalent lead-like compounds is reported, utilizing legacy compounds, robust library chemistry, and acquisitions. The lead-like covalent library was screened against the antiapoptotic protein Bfl-1, and six promising hits that displaced the BIM peptide from the PPI interface were identified. Intriguingly, X-ray crystallography of lead-like compound 8 showed that it binds to a previously unobserved conformation of the Bfl-1 protein and is an ideal starting point for the optimization of Bfl-1 inhibitors.

First large-scale study reveals important losses of managed honey bee and stingless bee colonies in Latin America.

Over the last quarter century, increasing honey bee colony losses motivated standardized large-scale surveys of managed honey bees (Apis mellifera), particularly in Europe and the United States. Here we present the first large-scale standardized survey of colony losses of managed honey bees and stingless bees across Latin America. Overall, 1736 beekeepers and 165 meliponiculturists participated in the 2-year survey (2016-2017 and 2017-2018). On average, 30.4% of honey bee colonies and 39.6% of stingless bee colonies were lost per year across the region. Summer losses were higher than winter losses in stingless bees (30.9% and 22.2%, respectively) but not in honey bees (18.8% and 20.6%, respectively). Colony loss increased with operation size during the summer in both honey bees and stingless bees and decreased with operation size during the winter in stingless bees. Furthermore, losses differed significantly between countries and across years for both beekeepers and meliponiculturists. Overall, winter losses of honey bee colonies in Latin America (20.6%) position this region between Europe (12.5%) and the United States (40.4%). These results highlight the magnitude of bee colony losses occurring in the region and suggest difficulties in maintaining overall colony health and economic survival for beekeepers and meliponiculturists.

Predisposing risk factors for cleft lip and palate in an Amazonian population by focusing on nutritional factors: A case-control study.

BACKGROUND: Orofacial clefts (OFC) are the most common congenital malformation of the craniofacial skeleton. Attempts have been made to correlate the components of maternal diet as triggers for the development or prevention of OFC. OBJECTIVE: To analyze nutritional status as a predictive factor for the development of cleft lip and palate in an Amazonian population. METHODS: A total of 152 mothers within 3 months of delivery were interviewed for comparison: 51 mothers of children with nonsyndromic cleft lip and palate (CLP) (study group) and 101 mothers of children without OFC (control group). A food frequency questionnaire was used to assess maternal nutrition and to analyze the influence of macro- and micronutrients on the possible predisposition or protection for CLP. RESULTS: The study group showed higher percentage of lipid intake than did the control group (p = 0.01). Among the participants with no family history of OFC, the study group had a higher percentage of lipid intake (p = 0.002) and lower vegetable intake (p = 0.037). Maternal micronutrient intake among the participants with a positive family history was lower in the study group for vitamins B2 (p = 0.03), B5 (p = 0.036), E (p = 0.03), and folate (p = 0.022). CONCLUSIONS: Nutritional analysis indicated that higher maternal lipid intake increased the likelihood of having offsprings with nonsyndromic CLP. Moreover, families with a history of OFC and low maternal folate intake showed heightened risk of nonsyndromic CLP in their offsprings.