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Self-determination theory (Deci & Ryan, 2000) posits basic psychological need satisfaction (BPNS) as essential for optimal functioning and health. Grounded in this framework, the current study examined the role of BPNS in dancers' cognitive appraisals and hormonal and emotional responses to performance stress. Dancers reported their degree of BPNS 1 month before a solo performance. Threat and challenge appraisals of the solo were recorded 2 hr before the performance. Salivary cortisol and anxiety were measured 15 min before, and 15, 30, 45, and 60 min postperformance. Higher BPNS was associated with lower cortisol responses and anxiety intensity. Challenge appraisals mediated the association between BPNS and cortisol. Threat appraisals mediated the BPNS-anxiety intensity relationship. These findings point to the potential importance of performers' BPNS for optimal emotional and hormonal homeostasis in performance conditions. [ABSTRACT FROM AUTHOR]

Objective: Optimal vitamin D levels are associated with reduced cardiovascular and all-cause mortality. We investigated whether optimal 25-hydroxyvitamin D (25[OH]D) is protective in individuals with the metabolic syndrome.Research Design and Methods: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study is a cohort study of subjects referred for coronary angiography between 1997 and 2000, from which 1,801 with the metabolic syndrome were investigated. Mortality was tracked for a median of 7.7 years. Multivariable survival analysis was used to estimate the association between 25(OH)D levels and mortality.Results: Most subjects (92%) had suboptimal levels of 25(OH)D (<75 nmol/L), with 22.2% being severely deficient (<25 nmol/L). During follow-up, 462 deaths were recorded, 267 (57.8%) of which were cardiovascular in origin. After full adjustment, including the metabolic syndrome components, those with optimal 25(OH)D levels showed a substantial reduction in all-cause (hazard ratio [HR] 0.25 [95% CI 0.13-0.46]) and cardiovascular disease mortality (0.33 [0.16-0.66]) compared with those with severe vitamin D deficiency. For specific cardiovascular disease mortality, there was a strong reduction for sudden death (0.15 [0.04-0.63]) and congestive heart failure (0.24 [0.06-1.04]), but not for myocardial infarction. The reduction in mortality was dose-dependent for each of these causes.Conclusions: Optimal 25(OH)D levels substantially lowered all-cause and cardiovascular disease mortality in subjects with the metabolic syndrome. These observations call for interventional studies that test whether vitamin D supplementation provides a useful adjunct in reducing mortality in these subjects. [ABSTRACT FROM AUTHOR]

Abstract Background Rescuing amphibian diversity is an achievable conservation challenge. Disease mitigation is one essential component of population management. Here we assess existing disease mitigation strategies, some in early experimental stages, which focus on the globally emerging chytrid fungus Batrachochytrium dendrobatidis. We discuss the precedent for each strategy in systems ranging from agriculture to human medicine, and the outlook for each strategy in terms of research needs and long-term potential. Results We find that the effects of exposure to Batrachochytrium dendrobatidis occur on a spectrum from transient commensal to lethal pathogen. Management priorities are divided between (1) halting pathogen spread and developing survival assurance colonies, and (2) prophylactic or remedial disease treatment. Epidemiological models of chytridiomycosis suggest that mitigation strategies can control disease without eliminating the pathogen. Ecological ethics guide wildlife disease research, but several ethical questions remain for managing disease in the field. Conclusions Because sustainable conservation of amphibians in nature is dependent on long-term population persistence and co-evolution with potentially lethal pathogens, we suggest that disease mitigation not focus exclusively on the elimination or containment of the pathogen, or on the captive breeding of amphibian hosts. Rather, successful disease mitigation must be context specific with epidemiologically informed strategies to manage already infected populations by decreasing pathogenicity and host susceptibility. We propose population level treatments based on three steps: first, identify mechanisms of disease suppression; second, parameterize epizootiological models of disease and population dynamics for testing under semi-natural conditions; and third, begin a process of adaptive management in field trials with natural populations.

Aims: Coronary artery disease (CAD) is a highly prevalent disease with modifiable risk factors. In patients with suspected obstructive CAD, evaluating the pre-test probability model is crucial for diagnosis, although its accuracy remains controversial. Machine learning (ML) predictive models can help clinicians detect CAD early and improve outcomes. This study aimed to identify early-stage CAD using ML in conjunction with a panel of clinical and laboratory tests., Methods and Results: The study sample included 3316 patients enrolled in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. A comprehensive array of attributes was considered, and an ML pipeline was developed. Subsequently, we utilized five approaches to generating high-quality virtual patient data to improve the performance of the artificial intelligence models. An extension study was carried out using data from the Young Finns Study (YFS) to assess the results' generalizability. Upon applying virtual augmented data, accuracy increased by approximately 5%, from 0.75 to -0.79 for random forests (RFs), and from 0.76 to -0.80 for Gradient Boosting (GB). Sensitivity showed a significant boost for RFs, rising by about 9.4% (0.81-0.89), while GB exhibited a 4.8% increase (0.83-0.87). Specificity showed a significant boost for RFs, rising by ∼24% (from 0.55 to 0.70), while GB exhibited a 37% increase (from 0.51 to 0.74). The extension analysis aligned with the initial study., Conclusion: Accurate predictions of angiographic CAD can be obtained using a set of routine laboratory markers, age, sex, and smoking status, holding the potential to limit the need for invasive diagnostic techniques. The extension analysis in the YFS demonstrated the potential of these findings in a younger population, and it confirmed applicability to atherosclerotic vascular disease., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The ability to independently control gene expression in two different tissues in the same animal is emerging as a major need, especially in the context of inter-organ communication studies. This type of study is made possible by technologies combining the GAL4/UAS and a second binary expression system such as the LexA system or QF system. Here, we describe a resource of reagents that facilitate combined use of the GAL4/UAS and a second binary system in various Drosophila tissues. Focusing on genes with well-characterized GAL4 expression patterns, we generated a set of more than 40 LexA-GAD and QF2 insertions by CRISPR knock-in and verified their tissue specificity in larvae. We also built constructs that encode QF2 and LexA-GAD transcription factors in a single vector. Following successful integration of this construct into the fly genome, FLP/FRT recombination is used to isolate fly lines that express only QF2 or LexA-GAD. Finally, using new compatible shRNA vectors, we evaluated both LexA and QF systems for in vivo gene knockdown and are generating a library of such RNAi fly lines as a community resource. Together, these LexA and QF system vectors and fly lines will provide a new set of tools for researchers who need to activate or repress two different genes in an orthogonal manner in the same animal., Competing Interests: JZ, BJ, RL, BE, JB, AR, CF, CV, YH, NP No competing interests declared, (© 2023, Zirin et al.)

The aims of this study were to retrospectively assess the occurrence of complications or need for secondary wrist procedures after the Sauvé-Kapandji procedure, and to prospectively assess patient-reported outcomes at long-term follow-up. All patients treated with the Sauvé-Kapandji procedure in our tertiary referral hospital between January 2008 and September 2021 were identified and contacted to complete the Quick Disabilities of the Arm, Shoulder, and Hand and the Patient-Rated Wrist/Hand Evaluation outcome measures. In total, 30 patients, with a median follow-up of 82 months, were included in this study. Complications occurred in 6 of 30 patients, which resulted in six secondary wrist procedures. Mean Quick Disabilities of the Arm, Shoulder, and Hand and Patient-Rated Wrist/Hand Evaluation scores were 30.1 and 33.6, respectively. We conclude that in respect of long-term outcomes, the Sauvé-Kapandji procedure can still be deemed to be a useful procedure, especially in patients with few other reconstructive options. Level of evidence: IV., Competing Interests: Declaration of conflicting interestsThe author(s) declared no conflicts of interest in terms of research, authorship, and/or publication of this article.

The diversity of CRISPR systems, coupled with scientific ingenuity, has led to an explosion of applications; however, to test newly described innovations in their model systems, researchers typically embark on cumbersome, one-off cloning projects to generate custom reagents that are optimized for their biological questions. Here, we leverage Golden Gate cloning to create the Fragmid toolkit, a modular set of CRISPR cassettes and delivery technologies, along with a web portal, resulting in a combinatorial platform that enables scalable vector assembly within days. We further demonstrate that multiple CRISPR technologies can be assessed in parallel in a pooled screening format using this resource, enabling the rapid optimization of both novel technologies and cellular models. These results establish Fragmid as a robust system for the rapid design of CRISPR vectors, and we anticipate that this assembly approach will be broadly useful for systematic development, comparison, and dissemination of CRISPR technologies., Competing Interests: Declaration of interests E.J.S. is a co-founder, scientific advisor, and equity holder of Intellia Therapeutics and a member of the scientific advisory board of Tessera Therapeutics. J.G.D. consults for Microsoft Research, BioNTech, Servier, and Pfizer. J.G.D. consults for and has equity in Tango Therapeutics. J.G.D. serves as a paid scientific advisor to the Laboratory for Genomics Research, funded in part by GSK, and the Innovative Genomics Institute, funded in part by Apple Tree Partners. J.G.D. receives funding support from the Functional Genomics Consortium: Abbvie, Bristol Myers Squibb, Janssen, and Merck. J.G.D.’s interests are reviewed and managed by the Broad Institute in accordance with its conflict of interest policies., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Unintentional falls are common among the elderly and given the expected increase of the aging population, these falls contribute to a high number of admissions to the emergency department. Relatively low-energy trauma mechanisms can lead to serious injuries in the elderly, with contributing factors being comorbidities, medication use and degenerative abnormalities., Case Presentation: A 94-year-old female suffered an unintentional fall at home. Upon arrival of the ambulance at her house she was hemodynamically stable and mobilized to the gurney with assistance. During primary survey at the emergency department, her blood pressure and oxygen saturation decreased, she was not able to move her legs anymore and lost consciousness. A full-body CTA was performed, which showed a fracture through the vertebral body of L2 with significant dislocation and a large active bleeding of the corpus, extending to the retroperitoneum and the epidural space. Despite resuscitation, her vital signs deteriorated and given the severe abnormalities on CTA, it was decided to discontinue further treatment, after which she deceased. The performed CTA and an x-ray from 2016 suggested diffuse idiopathic skeletal hyperostosis, which might have contributed to the severity and instability of the vertebral fracture. Mobilization after the fall might have increased the dislocation of the fracture. The use of oral anticoagulants worsened the subsequent bleeding and the extension to the epidural space caused the paralysis of the legs., Conclusions: It is important to be aware of the possible serious consequences of unintentional falls in the elderly population and to provide strict immobilization of the spinal column until proper imaging., (© 2024. The Author(s).)

Background: Cardiac rehabilitation (CR) reduces recurrent cardiac events and mortality in patients with cardiovascular diseases (CVD). Innovative eHealth methods can facilitate CR uptake and effectiveness by addressing barriers associated with clinic-based rehabilitation. Tailoring eHealth-based CR to patient preferences is needed to further enhance CR., Purpose: To identify preferred behavior change techniques (BCTs) as well as barriers and facilitators for the different health behaviors targeted in eHealth-based CR among patients who have been referred to CR., Methods: Thirty-nine patients were interviewed in nine focus groups in The Netherlands, Germany, and Spain. A thematic analysis, using a combined deductive and inductive approach to coding, was conducted to identify BCTs and barriers and facilitators to behavior change. Behaviors under investigation included physical activity, medication adherence, eating a cardiac healthy-diet, stress reduction and smoking cessation., Results: The perceived helpfulness of BCTs depended on the specific behavior targeted. Common barriers were negative emotional state and physical limitations. A desire to feel physically or mentally well and having experienced a cardiac life event were the most common facilitators across health behaviors. Specific BCTs, barriers and facilitators were found for each of the health behavior., Conclusions: Behavior change techniques that patients preferred for each health behavior targeted in eHealth-based CR were identified. A negative emotional state, experiencing a life event, and improving physical functioning are important barriers and facilitators in multiple behaviors targeted in eHealth-based CR programs. Additional tailoring of interventions to patient preferences for BCTs and patient-specific barriers and facilitators per health behavior could lead to further improvement of eHealth-based CR., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Short polypeptides encoded by small open reading frames (smORFs) are ubiquitously found in eukaryotic genomes and are important regulators of physiology, development, and mitochondrial processes. Here, we focus on a subset of 298 smORFs that are evolutionarily conserved between Drosophila melanogaster and humans. Many of these smORFs are conserved broadly in the bilaterian lineage, and ∼182 are conserved in plants. We observe remarkably heterogeneous spatial and temporal expression patterns of smORF transcripts-indicating wide-spread tissue-specific and stage-specific mitochondrial architectures. In addition, an analysis of annotated functional domains reveals a predicted enrichment of smORF polypeptides localizing to mitochondria. We conduct an embryonic ribosome profiling experiment and find support for translation of 137 of these smORFs during embryogenesis. We further embark on functional characterization using CRISPR knockout/activation, RNAi knockdown, and cDNA overexpression, revealing diverse phenotypes. This study underscores the importance of identifying smORF function in disease and phenotypic diversity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Depression is associated with metabolic alterations including lipid dysregulation, whereby associations may vary across individual symptoms. Evaluating these associations using a network perspective yields a more complete insight than single outcome-single predictor models., Methods: We used data from the Netherlands Study of Depression and Anxiety ( N = 2498) and leveraged networks capturing associations between 30 depressive symptoms (Inventory of Depressive Symptomatology) and 46 metabolites. Analyses involved 4 steps: creating a network with Mixed Graphical Models; calculating centrality measures; bootstrapping for stability testing; validating central, stable associations by extra covariate-adjustment; and validation using another data wave collected 6 years later., Results: The network yielded 28 symptom-metabolite associations. There were 15 highly-central variables (8 symptoms, 7 metabolites), and 3 stable links involving the symptoms Low energy (fatigue), and Hypersomnia. Specifically, fatigue showed consistent associations with higher mean diameter for VLDL particles and lower estimated degree of (fatty acid) unsaturation. These remained present after adjustment for lifestyle and health-related factors and using another data wave., Conclusions: The somatic symptoms Fatigue and Hypersomnia and cholesterol and fatty acid measures showed central, stable, and consistent relationships in our network. The present analyses showed how metabolic alterations are more consistently linked to specific symptom profiles.

Background: During Intensive Care Unit (ICU) admission, patients demonstrate up to 15% muscle loss per week, contributing to neuromuscular weakness, complicating recovery and delaying return to daily life. Biomarkers for muscle loss could aid in early detection of patients at risk and help guide resources to mitigate muscle loss, e.g. physical therapy and protein supplementation., Aims: To explore serum biomarkers for muscle mass and muscle loss in ICU patients using a metabolomics approach., Methods: Mechanically ventilated patients with an unplanned ICU admission between June and December 2021 were prospectively studied. The cross-sectional area of the rectus femoris muscle was assessed using ultrasound (RF csa ) and 188 serum metabolites were assessed using the Biocrates™ AbsoluteIDQ p180 kit for targeted metabolomics. Patients were eligible for analysis when a serum sample drawn within 5 days of ICU admission and at least 1 RF csa were available. In patients with sequential RF csa measurements, muscle loss was defined as the negative slope of the regression line fitted to the RF csa measurements per patient in the first 10 days of ICU admission. Correlations between baseline metabolite concentrations and baseline muscle mass, as well as between baseline metabolite concentrations and muscle loss were assessed using Pearson's test for correlations. To correct for multiple testing, the Benjamini-Hochberg procedure was used., Results: Seventeen patients were eligible for analysis. Mean age was 62 (SD ± 9) years and the cohort was predominantly male (76%). Four metabolites correlated with baseline muscle mass: creatinine (R = 0.5, p = 0.041), glycerophospholipid PC&#95;ae&#95;C30&#95;0 (R = 0.5, p = 0.034) and two acylcarnitines: C14&#95;2 (R = 0.5, p = 0.042) and C10&#95;2 (R = 0.5, p = 0.049). For muscle loss, significant associations were found for histidine (R = -0.8, p = 0.002) and three glycerophospholipids; PC&#95;aa&#95;C40&#95;2 (R = 0.7, p = 0.015), PC&#95;ae&#95;C40&#95;1 (R = 0.6, p = 0.032) and PC&#95;aa&#95;C42&#95;1 (R = 0.6, p = 0.037). After correction for multiple testing, no significant associations remained., Conclusions: This exploratory analysis found certain metabolites to be associated with muscle mass and muscle loss. Future research, specifically addressing these metabolites is necessary to confirm or refute an association with muscle loss and determine their role as potential muscle loss marker., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)