Standardising health history and injury surveillance of participants in endurance events: a modified Delphi consensus statement from the AMSSM runner health consortium.

Endurance events are popular worldwide and have many health benefits. However, runners and Para athletes may sustain musculoskeletal injuries or experience other health consequences from endurance events. The American Medical Society for Sports Medicine (AMSSM) Runner Health Consortium aimed to generate consensus-based survey items for use in prospective research to identify risk factors for injuries in runners and Para athletes training and competing in endurance events. The study design employed a modified Delphi approach, with a panel comprising 28 experts, including healthcare professionals, coaches, and athletes. Potential survey items were generated by panel members who subsequently engaged in three rounds of voting using Research Electronic Data Capture. Items were graded by clarity, relevance, and importance. Items achieving 80% consensus on all three aspects were retained. The response rate was 100% in R round 1 and 96% in Rrounds 2 and 3. Of 124 initial survey items, consensus was reached on 53, 34 and 22 items during Rrounds 1, 2, and 3, respectively. Two accepted items were removed due to redundancy. Combined with 10 non-voting items, 117 items covered key domains, including training and injury history, dietary behaviours and associated factors (such as menstrual function), footwear, mental health, and specific considerations for Para athletes. The consensus-based survey items should be considered by researchers to better understand the health of runners and Para athletes who train and compete in endurance sports to identify risk factors for injury.

A Dominance Hypothesis Argument for Historical Genetic Gains and the Fixation of Heterosis in Octoploid Strawberry.

Heterosis was the catalyst for the domestication of cultivated strawberry (Fragaria × ananassa), an interspecific hybrid species that originated in the 1700s. The hybrid origin was discovered because the phenotypes of spontaneous hybrids transgressed those of their parent species. The transgressions included fruit yield increases and other genetic gains in the twentieth century that sparked the global expansion of strawberry production. The importance of heterosis to the agricultural success of the hybrid species, however, has remained a mystery. Here we show that heterosis has disappeared (become fixed) among improved hybrids within a population (the California population) that has been under long-term selection for increased fruit yield, weight, and firmness. We found that the highest yielding hybrids are among the most highly inbred (59-79%), which seems counterintuitive for a highly heterozygous, outbreeder carrying heavy genetic loads. Although faint remnants of heterosis were discovered, the between-parent allele frequency differences and dispersed favorable dominant alleles necessary for heterosis have decreased nearly genome-wide within the California population. Conversely, heterosis was prevalent and significant among wide hybrids, especially for fruit count, a significant driver of genetic gains for fruit yield. We attributed the disappearance (fixation) of heterosis within the California population to increased homozygosity of favorable dominant alleles and inbreeding associated with selection, random genetic drift, and selective sweeps. Despite historical inbreeding, the highest yielding hybrids reported to-date are estimated to be heterozygous for 20,370-44,280 of 97,000-108,000 genes in the octoploid genome, the equivalent of an entire diploid genome or more.

WHO research agenda on the role of the institutional safety climate for hand hygiene improvement: a Delphi consensus-building study.

BACKGROUND: Creating and sustaining an institutional climate conducive to patient and health worker safety is a critical element of successful multimodal hand hygiene improvement strategies aimed at achieving best practices. Repeated WHO global surveys indicate that the institutional safety climate consistently ranks the lowest among various interventions. METHODS: To develop an international expert consensus on research agenda priorities related to the role of institutional safety climate within the context of a multimodal hand hygiene improvement strategy, we conducted a structured consensus process involving a purposive sample of international experts. A preliminary list of research priorities was formulated following evidence mapping, and subsequently refined through a modified Delphi consensus process involving two rounds. In round 1, survey respondents were asked to rate the importance of each research priority. In round 2, experts reviewed round 1 ratings to reach a consensus (defined as ≥70% agreement) on the final prioritised items to be included in the research agenda. The research priorities were then reviewed and finalised by members of the WHO Technical Advisory Group on Hand Hygiene Research in Healthcare. RESULTS: Of the 57 invited participants, 50 completed Delphi round 1 (88%), and 48 completed round 2 (96%). Thirty-six research priority statements were included in round 1 across five thematic categories: (1) safety climate; (2) personal accountability for hand hygiene; (3) leadership; (4) patient participation and empowerment and (5) religion and traditions. In round 1, 75% of the items achieved consensus, with 9 statements carried forward to round 2, leading to a final set of 31 prioritised research statements. CONCLUSION: This research agenda can be used by researchers, clinicians, policy-makers and funding bodies to address gaps in hand hygiene improvement within the context of an institutional safety climate, thereby enhancing patient and health worker safety globally.

Diverse Social Media Experiences and Adolescents' Depressive Symptoms: The Moderating Role of Neurobiological Responsivity to Rejected Peers.

Adolescents' experiences with social media are complex and can impact their mental well-being differently. Our study aimed to understand how neurobiological sensitivities may moderate the association between different social media experiences and depressive symptoms. In a multi-wave study, 80 adolescents (Mage = 13.06, SD = .58) took part in an fMRI task designed to gauge the neural responses when viewing accepted and rejected peers within their own social networks (wave 1). We also collected self-reported measures of positive (digital social connection) and negative (digital pressure) experiences on social media and depressive symptoms (waves 2 and 3). Our findings revealed that there were no significant associations between digital social connection, digital pressure, and depressive symptoms one year later. However, the association between digital social connection and depressive symptoms was moderated by neural responsivity. Specifically, for adolescents with reduced sensitivity to their rejected peers in the VS, rTPJ, and vmPFC, digital social connection was associated with reduced depressive symptoms one year later. These results emphasize the importance of individual differences in how adolescents' brains respond to rejected peers in shaping the impact of online experiences on their mental well-being.

Proximity Within Adolescent Peer Networks Predicts Neural Similarity During Affective Experience.

Individuals befriend others who are similar to them. One important source of similarity in relationships is similarity in felt emotion. In the present study, we used novel methods to assess whether greater similarity in the multivoxel brain representation of affective stimuli was associated with adolescents' proximity within real-world school-based social networks. We examined dyad-level neural similarity within a set of brain regions associated with the representation of affect including the ventromedial prefrontal cortex (vmPFC), amygdala, insula, and temporal pole. Greater proximity was associated with greater vmPFC neural similarity during pleasant and neutral experiences. Moreover, we used unsupervised clustering on social networks to identify groups of friends and observed that individuals from the same (verses different) friend groups were more likely to have greater vmPFC neural similarity during pleasant and negative experiences. These findings suggest that similarity in the multivoxel brain representation of affect may play an important role in adolescent friendships.

Silicone on the Move: Migratory Siliconoma After Retinal Surgery Report of a Case and Review of the Literature.

ABSTRACT: Silicone granulomas, or "siliconomas," are the common foreign-body inflammatory responses to injected silicone material. In rare cases, siliconomas develop remotely from the original site of injection, secondary to silicone migration. If a history of silicone injection is not noted, such lesions risk misdiagnosis (possibly as infection or malignancy). Intraocular silicone oil is commonly used in retinal detachment surgery, with occasional reports of granulomatous responses after its application in this context. Here, we report a 66-year-old man who developed a periocular silicone granuloma years after scleral buckle surgery for a detached retina and summarize the literature of similar reports of migratory siliconoma.

Muscular dystrophy as a cause of unilateral scapular winging.

Shoulder weakness with unilateral scapular winging is a common issue that initially presents to the general physician, sports physician or rheumatologist. Although most of these cases are neurogenic in nature, it is important to consider alternative causes for unilateral scapular winging. Muscular dystrophies can present with marked asymmetry, the most typical being facioscapulohumeral dystrophy (FSHD). We describe a case of FSHD with a summary of the key clinical features to increase the awareness of this condition among physicians.

Engineering Hyperechogenic Colloids with Clot-Targeting Capabilities from Platelet-Derived Membranes.

Thrombosis-related cardiovascular diseases remain the leading global cause of mortality and morbidity. In this study, we present a pioneering approach in the field of nanobiotechnology, with a focus on clinical translation, aimed at advancing early diagnosis and enhancing treatment options for thrombotic disorders. We introduce the fabrication of Platelet Membrane-Derived Bubbles (PMBs), which exhibit distinctive characteristics compared to conventional nanoparticles. These PMBs possess an average diameter of 700 nm and a negative ζ-potential, mirroring the attributes of parent platelet membranes. Utilizing diagnostic ultrasound imaging, we demonstrated the ability to visualize PMBs as hyperechogenic entities in agarose phantoms in vitro and in live mice in vivo. Furthermore, through confocal laser microscopy, we verified the retention of crucial transmembrane proteins, such as CD41 (GPIIb) and CD42 (GPIb), pivotal in conferring platelet-specific targeting functions. Importantly, our platelet aggregation studies confirmed that PMBs do not induce platelet aggregation but instead adhere to preformed platelet-rich in vitro thrombi. Overall, our work showcases the safe and precise utilization of PMBs to directly target acute thrombosis induced by laser injury in murine mesenteric veins in vivo, as visualized through intravital microscopy. In conclusion, we have successfully developed a rapid method for generating PMBs with unique ultrasound-directed and thrombus-targeting properties. These exceptional attributes of PMBs hold significant promise for advancing the field of ultrasound diagnostic thrombus imaging and clot-targeted therapy in the clinical context.

Aging disrupts blood-brain and blood-spinal cord barrier homeostasis, but does not increase paracellular permeability.

Blood-CNS barriers protect the CNS from circulating immune cells and damaging molecules. It is thought barrier integrity becomes disrupted with aging, contributing to impaired CNS function. Using genome-wide and targeted molecular approaches, we found aging affected expression of predominantly immune invasion and pericyte-related genes in CNS regions investigated, especially after middle age, with spinal cord being most impacted. We did not find significant perturbation of endothelial cell junction genes or proteins, nor were vascular density or pericyte coverage affected by aging. We evaluated barrier paracellular permeability using small molecular weight tracers, serum protein extravasation, CNS water content, and iron labelling measures. We found no evidence for age-related increased barrier permeability in any of these tests. We conclude that blood-brain (BBB) and blood-spinal cord barrier (BSCB) paracellular permeability does not increase with normal aging in mouse. Whilst expression changes were not associated with increased permeability, they may represent an age-related primed state whereby additional insults cause increased leakiness.

Personal Relative Deprivation and Locus of Control.

OBJECTIVE: We investigated the relationship between personal relative deprivation (PRD)-resentment from the belief that one is worse off than people who are similar to oneself-and locus of control. BACKGROUND: Research has yet to comprehensively investigate whether PRD is associated with a tendency to favor external (vs. internal) explanations for self- and other-relevant outcomes. METHOD: Eight studies (Ntotal = 6729) employed cross-sectional, experimental, and (micro)longitudinal designs and used established trait and state measures of PRD and loci of control. RESULTS: Participants higher in PRD adopted more external (vs. internal) explanations for others' outcomes while controlling for socio-demographics (e.g., socioeconomic status; Studies 1-4). This relationship was mediated by a lowered sense of personal control (Study 1) and evident in a cross-national sample of participants in Asia (Study 2). PRD is more robustly associated with external than internal explanations for self and other-relevant outcomes (Studies 5-8), and within-person changes in PRD are positively associated with within-person changes in external explanations (month-to-month and day-to-day; Studies 7-8). CONCLUSIONS: PRD is positively associated with external locus of control independent of socioeconomic status, within and between people, and across cultures. This research highlights the implications of PRD for people's construal of the causal forces that govern their lives.

Cyclic Glycopeptide Analogs of Endomorphin-1 Provide Highly Effective Antinociception in Male and Female Mice.

Opioids acting at the mu opioid receptor (MOR) remain the most effective treatment for moderate to severe pain, but their use is limited by serious side effects. We have shown that a cyclized analog of endomorphin-1 provided pain relief comparable to that of morphine with reduction or absence of several side effects, including abuse liability. Glycosylation can promote penetration of cellular barriers. Here we developed cyclic glycopeptide endomorphin (glycoEM) analogs as drug candidates for potent and long-lasting analgesia. The analogs were assessed in receptor binding and functional assays and for blood-brain barrier penetration by microdialysis and MS. Two of the analogs showed MOR selectivity and more potent and longer lasting antinociception than morphine in male and female mice. Comparable antinociception occurred at A2 doses 5-fold lower (20-fold on a molar basis) than morphine doses. The results support further study of the glycoEMs for clinical application.

Mental health symptom burden in elite ice hockey players and its association with self-reported concussive events.

BACKGROUND: Some studies suggest that elite athletes experience adverse mental health symptoms at rates commensurate with the general population, despite the well-established buffering effects of exercise. Within contact sports, such as ice-hockey, recurrent concussions may be a source of this discrepancy. We compared the point prevalence of various mental health outcomes with other athlete and general population samples, as well as investigated their relationship with concussive events. METHODS: We surveyed 648 active ice hockey players from the top two men's tiers and the top women's tier in Swedish elite ice hockey on lifetime concussive events, hazardous alcohol use, problematic social media use, depression, anxiety, and burnout. RESULTS: Hazardous alcohol use was more prevalent among male ice hockey players (29.5% AUDIT-C ≥ 6) compared to other athlete and general population samples, while other mental health symptoms were less common. Female ice hockey players reported higher hazardous alcohol consumption (36.4% AUDIT-C ≥ 4) than another athlete sample and more burnout (19.1%) than the general population. After adjusting for covariates, athletes with 3+ concussive events had 2.1 times the odds of elevated depressive symptoms and 3.5 times the odds of elevated burnout symptoms compared to those with no concussion history. Treating lifetime concussive events as a continuous predictor revealed positive correlations with all outcomes except for hazardous alcohol use. CONCLUSIONS: Mental health outcome rates among active elite ice hockey athletes differ from those of other athlete and general population samples, whilst concussive events may be particularly linked to elevated symptoms of depression and burnout.

LAIR-1 and PECAM-1 function via the same signaling pathway to inhibit GPVI-mediated platelet activation.

Background: Inhibition of platelet responsiveness is important for controlling thrombosis. It is well established that platelet endothelial cell adhesion molecule-1 (PECAM-1) serves as a physiological negative regulator of platelet-collagen interactions. We recently demonstrated that leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a negative regulator of platelet production and reactivity. It is however not known if LAIR-1 and PECAM-1 function in the same or different inhibitory pathways. Objectives: In this study, we investigated the role of LAIR-1 alongside PECAM-1 in megakaryocyte development and platelet production and determined the functional redundancy through characterization of a LAIR-1/PECAM-1 double knockout (DKO) mouse model. Methods: LAIR-1 and PECAM-1 expression in megakaryocytes were evaluated by western blotting. Megakaryocyte ploidy and proplatelet formation were evaluated by flow cytometry and fluorescent microscopy. Platelet function and signalling were compared in wild-type, LAIR-1 -/- , PECAM-1 -/-  and DKO mice using aggregometry, flow cytometry and western blotting. Thrombosis was evaluated using the FeCl 3  carotid artery model. Results: We show that LAIR-1/PECAM-1 DKO mice exhibit a 17% increase in platelet count. Bone marrow-derived megakaryocytes from all 3 mouse models had normal ploidy in vitro, suggesting that neither LAIR-1 nor PECAM-1 regulates megakaryocyte development. Furthermore, relative to wild-type platelets, platelets derived from LAIR-1, PECAM-1, and DKO mice were equally hyperresponsive to collagen in vitro, indicating that LAIR-1 and PECAM-1 participate in the same inhibitory pathway. Interestingly, DKO mice exhibited normal thrombus formation in vivo due to DKO mouse platelets lacking the enhanced Src family kinase activation previously shown in platelets from LAIR-1-deficient mice. Conclusion: Findings from this study reveal that LAIR-1 and PECAM-1 act to inhibit GPVI-mediated platelet activation via the same signaling pathway. Mice lacking LAIR-1 and PECAM-1 do not however exhibit an increase in thrombus formation despite minor increase in platelet count and reactivity to collagen. This study adds to the growing evidence that immunoreceptor tyrosine-based inhibition motif-containing receptors are important regulators of platelet count and function.

On the Topotactic Phase Transition Achieving Superconducting Infinite-Layer Nickelates.

Topotactic reduction is critical to a wealth of phase transitions of current interest, including synthesis of the superconducting nickelate Nd0.8Sr0.2NiO2, reduced from the initial Nd0.8Sr0.2NiO3/SrTiO3 heterostructure. Due to the highly sensitive and often damaging nature of the topotactic reduction, however, only a handful of research groups have been able to reproduce the superconductivity results. A series of in situ synchrotron-based investigations reveal that this is due to the necessary formation of an initial, ultrathin layer at the Nd0.8Sr0.2NiO3 surface that helps to mediate the introduction of hydrogen into the film such that apical oxygens are first removed from the Nd0.8Sr0.2NiO3 / SrTiO3 (001) interface and delivered into the reducing environment. This allows the square-planar / perovskite interface to stabilize and propagate from the bottom to the top of the film without the formation of interphase defects. Importantly, neither geometric rotations in the square planar structure nor significant incorporation of hydrogen within the films is detected, obviating its need for superconductivity. These findings unveil the structural basis underlying the transformation pathway and provide important guidance on achieving the superconducting phase in reduced nickelate systems.

Rise in Gender Dysphoria Diagnoses and Legal Gender Changes in Sweden: 2005-2017.

Evidence suggests the incidence of gender dysphoria (GD), a condition characterized by psychological distress caused by a mismatch between an individual's gender identity and biological sex assigned as birth, has increased since the turn of the twenty-first century. We examined trends in the number of GD diagnoses and legal gender changes in Sweden using registry data from 5007 individuals diagnosed with GD between 2005 and 2017 (53.5% assigned female at birth). GD diagnoses increased substantially over time, especially in birth-assigned females and younger age groups. One-third of all subjects with GD legally changed their gender, with an increase of 1000% from 2005 to 2018. Generally, individuals who were assigned female at birth changed their gender earlier than birth-assigned males, and most did so within one year of GD diagnosis. Our findings highlight the need to analyze the causes and correlations of rapid changes in clinical presentation and to prepare healthcare systems for rising patient demand.

Time domain characterization of nonstationary low-Mach number aeroacoustic sources using principal component analysis.

This paper presents the use of principal component analysis (PCA) for time domain microphone array denoising to characterize an impulsive aeroacoustic source, which is illustrated with the aeroacoustic emission caused by a vortex ring/edge interaction. Prior studies have used signal processing approaches that required assumptions about the source directivity or user intervention at low signal-to-noise ratio (SNR) conditions. In this context, PCA, a matrix decomposition tool which identifies the most common features across an ensemble of observations, provides a data-driven (hands-off) approach to signal processing. For microphone array time series, particular attention is paid to the temporal alignment of the signals to facilitate PCA. A time domain approach is necessary when sources are impulsive and nonstationary. Two such signal arrangements are discussed in this work. Results from this method are in good agreement with theory, validated by prior results using an ensemble averaging approach requiring user support. Furthermore, the results of this method are improved when compared to the ensemble averaging approach without user intervention. A SNR limit is identified where PCA becomes less effective for the vortex/edge interaction problem. This SNR limit is intended to aid in the design of similar future experiments.

Radiation Oncology Opinions and Practice on Cardiotoxicity in Lung Cancer: A Cross-sectional Study by the International Cardio-oncology Society.

AIMS: Symptomatic radiation cardiotoxicity affects up to 30% patients with lung cancer and several heart substructure doses are associated with reduced overall survival. A greater focus on minimising cardiotoxicity is now possible due to advancements in radiotherapy technology and the new discipline of cardio-oncology, but uptake of emerging data has not been ascertained. A global cross-sectional analysis of Radiation Oncologists who treat lung cancer was therefore conducted by the International Cardio-Oncology Society in order to establish the impact of recently published literature and guidelines on practice. MATERIALS AND METHODS: A bespoke questionnaire was designed following an extensive review of the literature and from recurring relevant themes presented at Radiation Oncology and Cardio-Oncology research meetings. Six question domains were retained following consensus discussions among the investigators, comprising 55 multiple choice stems: guidelines, cardiovascular assessment, cardiology investigations, radiotherapy planning strategies, primary prevention prescribing and local cardio-oncology service access. An invitation was sent to all Radiation Oncologists registered with ICOS and to Radiation Oncology colleagues of the investigators. RESULTS: In total 118 participants were recruited and 92% were consultant physicians. The ICOS 2021 expert consensus statement was rated as the most useful position paper, followed by the joint ESC-ESTRO 2022 guideline. The majority (80%) of participants indicated that a detailed cardiovascular history was advisable. Although 69% of respondents deemed the availability of cardiac substructure auto-segmentation to be very/quite important, it was implemented by only a few, with the most common being the left anterior descending coronary artery V15. A distinct cardio-oncology service was available to 39% participants, while the remainder utilised general cardiology services. CONCLUSION: The uptake of recent guidelines on cardiovascular optimisation is good, but access to cardiology investigations and consultations, and auto-segmentation, represent barriers to modifying radiotherapy practices in lung cancer to reduce the risk of radiation cardiotoxicity.

Transcriptome- and proteome-wide association studies identify genes associated with renal cell carcinoma.

We performed a series of integrative analyses including transcriptome-wide association studies (TWASs) and proteome-wide association studies (PWASs) of renal cell carcinoma (RCC) to nominate and prioritize molecular targets for laboratory investigation. On the basis of a genome-wide association study (GWAS) of 29,020 affected individuals and 835,670 control individuals and prediction models trained in transcriptomic reference models, our TWAS across four kidney transcriptomes (GTEx kidney cortex, kidney tubules, TCGA-KIRC [The Cancer Genome Atlas kidney renal clear-cell carcinoma], and TCGA-KIRP [TCGA kidney renal papillary cell carcinoma]) identified 38 gene associations (false-discovery rate <5%) in at least two of four transcriptomic panels and identified 12 genes that were independent of GWAS susceptibility regions. Analyses combining TWAS associations across 48 tissues from GTEx identified associations that were replicable in tumor transcriptomes for 23 additional genes. Analyses by the two major histologic types (clear-cell RCC and papillary RCC) revealed subtype-specific associations, although at least three gene associations were common to both subtypes. PWAS identified 13 associated proteins, all mapping to GWAS-significant loci. TWAS-identified genes were enriched for active enhancer or promoter regions in RCC tumors and hypoxia-inducible factor binding sites in relevant cell lines. Using gene expression correlation, common cancers (breast and prostate) and RCC risk factors (e.g., hypertension and BMI) display genetic contributions shared with RCC. Our work identifies potential molecular targets for RCC susceptibility for downstream functional investigation.

Ionizable Drugs Enable Intracellular Delivery of Co-Formulated siRNA.

Targeting complementary pathways in diseases such as cancer can be achieved with co-delivery of small interfering ribonucleic acid (siRNA) and small molecule drugs; however, current formulation strategies are typically limited to one, but not both. Here, ionizable small molecule drugs and siRNA are co-formulated in drug-rich nanoparticles. Ionizable analogs of the selective estrogen receptor degrader fulvestrant self-assemble into colloidal drug aggregates and cause endosomal disruption, allowing co-delivery of siRNA against a non-druggable target. siRNA is encapsulated in lipid-stabilized, drug-rich colloidal nanoparticles where the ionizable lipid used in conventional lipid nanoparticles is replaced with an ionizable fulvestrant analog. The selection of an appropriate phospholipid and formulation buffer enables endocytosis and potent reporter gene knockdown in cancer cells. Importantly, siRNA targeting cyclin E1 is effectively delivered to drug-resistant breast cancer cells, demonstrating the utility of this approach. This strategy opens the possibility of using ionizable drugs to co-deliver RNA and ultimately improve therapeutic outcomes.