Rare genomic copy number variants implicate new candidate genes for bicuspid aortic valve.

Bicuspid aortic valve (BAV), the most common congenital heart defect, is a major cause of aortic valve disease requiring valve interventions and thoracic aortic aneurysms predisposing to acute aortic dissections. The spectrum of BAV ranges from early onset valve and aortic complications (EBAV) to sporadic late onset disease. Rare genomic copy number variants (CNVs) have previously been implicated in the development of BAV and thoracic aortic aneurysms. We determined the frequency and gene content of rare CNVs in EBAV probands (n = 272) using genome-wide SNP microarray analysis and three complementary CNV detection algorithms (cnvPartition, PennCNV, and QuantiSNP). Unselected control genotypes from the Database of Genotypes and Phenotypes were analyzed using identical methods. We filtered the data to select large genic CNVs that were detected by multiple algorithms. Findings were replicated in a BAV cohort with late onset sporadic disease (n = 5040). We identified 3 large and rare (< 1,1000 in controls) CNVs in EBAV probands. The burden of CNVs intersecting with genes known to cause BAV when mutated was increased in case-control analysis. CNVs intersecting with GATA4 and DSCAM were enriched in cases, recurrent in other datasets, and segregated with disease in families. In total, we identified potentially pathogenic CNVs in 9% of EBAV cases, implicating alterations of candidate genes at these loci in the pathogenesis of BAV.

Assessing the transportability of radiomic models for lung cancer diagnosis: commercial vs. open-source feature extractors.

Background: Radiomics has shown promise in improving malignancy risk stratification of indeterminate pulmonary nodules (IPNs) with many platforms available, but with no head-to-head comparisons. This study aimed to evaluate transportability of radiomic models across platforms by comparing performances of a commercial radiomic feature extractor (HealthMyne) with an open-source extractor (PyRadiomics) on diagnosis of lung cancer in IPNs. Methods: A commercial radiomic feature extractor was used to segment IPNs from computed tomography (CT) scans, and a previously validated radiomic model based on commercial features was used as baseline (ComRad). Using same segmentation masks, PyRadiomics, an open-source feature extractor was used to build three open-source radiomic models (OpenRad) using different methods: de novo open-source model derived using least absolute shrinkage and selection operator (LASSO) for feature selection, selecting open-source features matched to ComRad features based upon Imaging Biomarker Standardization Initiative (IBSI) nomenclature, and selecting open-source features most highly correlated to ComRad features. Radiomic models were trained on an internal cohort (n=161) and externally validated on 3 cohorts (n=278). We added Mayo clinical risk score to OpenRad and ComRad models, creating integrated clinical radiomic (ClinRad) models. All models were compared using area under the curve (AUC) and evaluated for clinical improvement using bias-corrected clinical net reclassification indices (cNRIs). Results: ComRad AUC was 0.76 [95% confidence interval (CI): 0.71-0.82], and OpenRad AUC was 0.75 (95% CI: 0.69-0.81) for LASSO model, 0.74 (95% CI: 0.68-0.79) for Spearman's correlation, and 0.71 (95% CI: 0.65-0.77) for IBSI. Mayo scores were added to OpenRad LASSO model, which performed best, forming open-source ClinRad model with AUC of 0.80 (95% CI: 0.74-0.86), identical to commercial ClinRad's AUC. Both ClinRad models showed clinical improvement compared to Mayo alone, with commercial ClinRad achieving cNRI of 0.09 (95% CI: 0.02-0.15) for benign and 0.07 (95% CI: 0.00-0.13) for malignant, and open-source ClinRad achieving cNRI of 0.09 (95% CI: 0.02-0.15) for benign and 0.06 (95% CI: 0.00-0.12) for malignant. Conclusions: Transportability of radiomic models across platforms directly does not conserve performance, but radiomic platforms can provide equivalent results when building de novo models allowing for flexibility in feature selection to maximize prediction accuracy.

Knowledge and intentions to use fertility preservation among urban Chinese cancer patients: A study from Hong Kong.

OBJECTIVE: To assess the knowledge levels and fertility preservation (FP) intentions of urban Chinese cancer patients. METHODS: A cross-sectional study was conducted on Hong Kong Chinese male and female cancer patients aged 18-54 years (N = 325) who were recruited by a local non-governmental organization for cancer patients between July 2020 to January 2021. Patients completed a self-administered questionnaire on knowledge, perceptions, and intentions to use FP services/seek FP-related information. Multivariable logistic regression was used to explore the correlates of intention to seek additional FP information and intention to undergo FP treatments. RESULTS: Although cancer patients demonstrated a good knowledge of the available FP treatment options, they were less knowledgeable about the legal restrictions of these procedures. Only one in seven cancer patients first became aware of FP through a health provider and the majority of cancer patients felt they did not have adequate knowledge about FP to make informed FP decisions at the current time. Yet, over one-third of cancer patients would consider FP options even if their cancer or cancer treatment had < 5% chance of causing infertility, and 13.4% of females and 14.6% of males would delay their cancer treatment by ≥ 3 months to undergo FP procedures. However, for both sexes, the main perceived barrier to obtaining FP was its financial cost. Patients with older-aged spouses were less likely to seek FP treatments or seek more information about FP. CONCLUSION: There is an unmet need for more FP information and FP services for reproductive-aged cancer patients in East Asian populations. Greater integration of FP services into cancer treatment requires a reduction of cost barriers, greater provision of timely FP information, and improved referral systems.

Host and antibiotic jointly select for greater virulence in Staphylococcus aureus.

Widespread antibiotic usage has resulted in the rapid evolution of drug-resistant bacterial pathogens and poses significant threats to public health. Resolving how pathogens respond to antibiotics under different contexts is critical for understanding disease emergence and evolution going forward. The impact of antibiotics has been demonstrated most directly through in vitro pathogen passaging experiments. Independent from antibiotic selection, interactions with hosts have also altered the evolutionary trajectories and fitness landscapes of pathogens, shaping infectious disease outcomes. However, it is unclear how interactions between hosts and antibiotics impact the evolution of pathogen virulence. Here, we evolved and re-sequenced Staphylococcus aureus , a major bacterial pathogen, varying exposure to host and antibiotics to tease apart the contributions of these selective pressures on pathogen adaptation. After 12 passages, S. aureus evolving in Caenorhabditis elegans nematodes exposed to a sub-minimum inhibitory concentration of antibiotic (oxacillin) became highly virulent, regardless of whether the ancestral pathogen was methicillin-resistant (MRSA) or methicillin-sensitive (MSSA). Host and antibiotic exposure selected for reduced drug susceptibility in MSSA lineages while increasing MRSA total growth outside hosts. We identified mutations in genes involved in complex regulatory networks linking virulence and metabolism, including codY , agr , and gdpP , suggesting that rapid adaptation to infect hosts may have pleiotropic effects. In particular, MSSA populations under selection from host and antibiotic accumulated mutations in the global regulator gene codY , which controls biofilm formation in S. aureus. These populations had indeed evolved more robust biofilms-a trait linked to both virulence and antibiotic resistance-suggesting evolution of one trait can confer multiple adaptive benefits. Despite evolving in similar environments, MRSA and MSSA populations proceeded on divergent evolutionary paths, with MSSA populations exhibiting more similarities across replicate populations. Our results underscore the importance of considering multiple and concurrent selective pressures as drivers of pervasive pathogen traits.

Osteoarthritis Year In Review 2024: Rehabilitation and outcomes.

This Year in Review presents key highlights from recent research relating to osteoarthritis rehabilitation and its outcomes, defined as any non-pharmacological and non-surgical treatment that aims to improve osteoarthritis symptoms at any joint. Three databases (Medline, Embase, and CINAHL Plus) were searched between 1 March 2023 to 12 March 2024. Relevant studies were chosen based on the predefined inclusion/exclusion criteria, perceived clinical importance, quality, controversy in the field, or personal interest, and organised into four overarching themes (with 1-5 sub-themes each). The first theme related to uncertainties regarding exercise benefits. New work has challenged the clinical effectiveness of exercise on symptoms, as well as highlighted uncertainty around our understanding of both mechanisms of effects, how to enhance effectiveness and adherence, and which subgroups of people are more or less likely to improve with exercise. However, we also highlight new work confirming the role of exercise as a first-line management strategy. The second theme related to digital modes of service delivery. There was new evidence to support its effectiveness in improving symptoms and clear potential for creating and evaluating new mobile apps. New work also highlighted the potential future role artificial intelligence can have in providing treatment information and recommendations. The third theme related to patient education, and the call for change to the impairment-based narrative that prevails in osteoarthritis information. The fourth theme is related to weight loss. New work compared the effectiveness of different weight loss diets and explored alternative models of weight loss delivery.

Torture Exposure Modulates Cognitive Control and Attention Neural Network Connectivity During a Go/Nogo Task.

BACKGROUND: Torture trauma is characterised by intentional uncontrollable acts, but the long-term effects of torture exposure on cognitive control brain mechanisms are unknown. METHODS: A final sample of 33 torture survivors (TS) and 44 non-torture survivors (NTS), all with a refugee background, completed a Go/NoGo response inhibition task during fMRI scanning. Data-driven independent components analysis identified active networks across the task, and within Go, NoGo and error of commission trials. Groups were compared on within/between network connectivity, controlling for demographic and psychological symptom covariates. Secondary analyses investigated whether network connectivity moderated the associations between torture exposure and severity on fear (e.g. re-experiencing) and dysphoria (e.g. anhedonia) posttraumatic stress disorder (PTSD) symptoms. RESULTS: The TS group exhibited decreased connectivity (compared to NTS controls) within the posterior default mode network (specifically the left precuneus) and auditory-motor network (specifically right superior temporal gyrus STG), and reduced connectivity between the dorsomedial frontal network (dmFN) and dorsal attention network (dAN) across the Go/NoGo task. The TS group also showed comparatively more negative ventral attention network connectivity during NoGo (i.e. inhibition) trials. No behavioral effects were observed. Secondary analyses revealed that association between torture exposure and elevated PTSD dysphoria (not fear) symptoms was moderated by reduced connectivity in the right STG and between the dmFN-dAN. CONCLUSIONS: Response inhibition, attention and motor networks appear less connected in torture survivors, which may be specifically linked to PTSD dysphoria symptom profiles. Findings suggest that targeting cognitive control processes may hold promise for alleviating post-traumatic symptoms amongst survivors of torture.

The growing research toolbox for SLC13A5 citrate transporter disorder: a rare disease with animal models, cell lines, an ongoing Natural History Study and an engaged patient advocacy organization.

TESS Research Foundation (TESS) is a patient-led nonprofit organization seeking to understand the basic biology and clinical impact of pathogenic variants in the SLC13A5 gene. TESS aims to improve the fundamental understanding of citrate's role in the brain, and ultimately identify treatments and cures for the associated disease. TESS identifies, organizes, and develops collaboration between researchers, patients, clinicians, and the pharmaceutical industry to improve the lives of those suffering from SLC13A5 citrate transport disorder. TESS and its partners have developed multiple molecular tools, cellular and animal models, and taken the first steps toward drug discovery and development for this disease. However, much remains to be done to improve our understanding of the disorder associated with SLC13A5 variants and identify effective treatments for this devastating disease. Here, we describe the available SLC13A5 resources from the community of experts, to foundational tools, to in vivo and in vitro tools, and discuss unanswered research questions needed to move closer to a cure.

Overview of research in SLC13A5 citrate transporter disorder SLC13A5 citrate transporter disorder is an ultra-rare, neurodevelopmental disorder that severely impacts cognition and motor control. It is characterized by frequent, intractable seizures that develop hours or days after birth, low tone, global developmental delay, a unique, varied, and difficult to categorize movement disorder, limited expressive verbal capabilities, tooth abnormalities, and increased citrate in both the CNS and serum. Seizures are frequently medically intractable, patients are often on multiple antiseizure medications and have frequent emergency room visits and hospitalizations for status epilepticus. SLC13A5 citrate transporter disorder is caused by mutations in the SLC13A5 gene which encodes a sodium-dependent citrate transporter, NaCT. NaCT is responsible for transporting citrate, a key molecule in cellular metabolism, from the extracellular space into cells, especially in the central nervous system and the liver. NaCT has been extensively studied in multiple animal models and affects lifespan and loss of some transporter activity actually improves metabolic syndrome in all animal species tested so far while causing mild neurological dysfunction in rodents. Although not definitively proven, it is presumed that loss of neuronal cell citrate transporter activity in the brain is the cause of seizures. Since the discovery of the disorder in 2014, there has been a rapid expansion in characterization of the disease. This has been aided by development of multiple models and molecular tools for studying wild type and mutant SLC13A5 making it a tractable candidate for therapeutic development. TESS Research Foundation is dedicated to driving SLC13A5 research and supporting children and families living with the disorder. Here, we describe the available SLC13A5 resources from the community of experts, to foundational tools, to in vivo and in vitro tools, and discuss unanswered research questions needed to move closer to a cure.

Implementation of aspirin use during pregnancy in community midwifery-led care in the Netherlands: A pilot survey.

INTRODUCTION: Aspirin nowadays is widely used in pregnancy, but implementation among gynecologists took nearly four decades. For a complete insight in the implementation of aspirin, community midwives are to be involved. Community midwives do not have authority to prescribe aspirin and have to refer to a general practitioner or consultant obstetrician for a prescription. METHODS: The study was an online, national pilot survey about the implementation of aspirin use during pregnancy among independently practicing community midwives consisting of 29 items with five categories: background, advising, prescribing, possible indications, and clinical practice. RESULTS: Forty-seven community midwives completed the survey between April and May 2021. All respondents had experience on advising aspirin use in pregnancy. History of preterm pre-eclampsia or HELLP syndrome was identified as a risk factor for developing utero-placental complications by 97.9% of the community midwives. Moderate risk factors in women with otherwise low-risk pregnancy were identified by >75% of the participants. Practical issues in prescribing aspirin were experienced by one-third of the respondents. Suggestions were made to obtain authority for community midwives to prescribe aspirin and improve collaboration with consultant obstetricians and general practitioners. CONCLUSIONS: Community midwives seem to be adequate in identifying risk factors for developing utero-placental complications in women with otherwise low-risk pregnancy. Practical issues for prescribing aspirin occur often. Obtaining authority for community midwives to prescribe aspirin after education should be considered and consulting a consultant obstetrician should become more accessible to overcome the practical issues. Further educating community midwives and general practitioners might improve implementation rates and perinatal outcomes.

Relational conflicts during COVID-19: Impact of loss and reduction of employment due to prevention measures and the influence of sex and stress (in the iCARE study).

This study explored the association between pandemic-related loss/reduction of employment, sex, COVID-19-related stress and relational conflicts. A sample of 5103 Canadians from the iCARE study were recruited through an online polling firm between October 29, 2020, and March 23, 2021. Logistic regressions revealed that participants with loss/reduction of employment were 3.6 times more likely to report increased relational conflicts compared to those with stable employment (OR = 3.60; 95% CIs = 3.03-4.26). There was a significant interaction between employment status and sex (x2 = 10.16; p < 0.005), where loss/reduction of employment was associated with more relational conflicts in males compared to females. There was a main effect of COVID-19-related stress levels on relational conflicts (increased stress vs no stress : OR = 9.54; 95% CIs = 6.70-13.60), but no interaction with loss/reduction of employment (x2 = 0.46, p = 0.50).

Longitudinal echocardiography in pediatric patients with hypermobile Ehlers-Danlos syndrome.

Vascular Ehlers-Danlos, Marfan and Loeys-Dietz syndromes have increased risk of aortic dilation and dissection. Previous early studies showed hypermobile Ehlers-Danlos syndrome (hEDS) may also have increased risk, with echocardiography screening recommended; subsequent studies have not confirmed the risk or recommended echocardiography. This pediatric-based study assessed aortic dilation prevalence in those with hEDS by serial echocardiographic examinations and assessed family history for aortic dissections. We retrospectively identified individuals with hEDS who had echocardiography studies from the electronic medical records at one pediatric center. Aortic root Z-scores >2.0 were found in 15/225 subjects (average age 12.9 years) on initial echocardiograms, with no Z-score >3.0. Subsequent studies (n = 68) found statistically significant decline in aortic root Z-scores. Repeat echocardiography in those with initial aortic root Z-score >2.0 (n = 10) demonstrated a decline in Z score <2.0 in seven. On final examination, 9/225 (4.0%) had a Z-score >2.0, not statistically different from the general population. No aortic dissection occurred in first- or second-degree relatives. In conclusion, aortic root dilation rate in hEDS is likely not different from the general population. We propose that in the absence of other cardiac findings or suspicion for another disorder, echocardiography is not required in hEDS.

Steroid profiling in human primary teeth via liquid chromatography-tandem mass spectrometry for long-term retrospective steroid measurement.

Steroid hormones are important modulators of many physiological processes, and measurements of steroids in blood, saliva, and urine matrices are widely used to assess endocrine pathologies and stress. However, these matrices cannot be used to retrospectively assess early-life stress and developmental endocrine pathologies, because they do not integrate steroid levels over the long term. A novel biological matrix in which to measure steroids is primary teeth (or "baby teeth"). Primary teeth develop early in life and accumulate various endogenous molecules during their gradual formation. Here, we developed and validated the first assay to measure steroids in human primary teeth using liquid chromatography-tandem spectrometry (LC-MS/MS). Our assay is highly sensitive, specific, accurate, and precise. It allows for the simultaneous quantification of 17 steroids in primary teeth (16 of which have not been examined previously in primary teeth). Overall, steroid levels in primary teeth were relatively low, and 8 steroids were quantifiable. Levels of dehydroepiandrosterone, cortisol, and progesterone were the highest of the 17 steroids examined. Next, we used this assay to perform steroid profiling in primary teeth from males and females. The same 8 steroids were quantifiable, and no sex differences were found. Levels of androgens (androstenedione and testosterone) were positively correlated, and levels of glucocorticoids (cortisol, cortisone, corticosterone, 11-dehydrocorticosterone) were also positively correlated. These data demonstrate that multiple steroids can be quantified by LC-MS/MS in human primary teeth, and this method potentially provides a powerful new way to retrospectively assess early-life stress and developmental endocrine pathologies.

Imprinted X chromosome inactivation in marsupials: The paternal X arrives at the egg with a silent DNA methylation profile.

X chromosome inactivation (XCI) is an epigenetic process that results in the transcriptional silencing of one X chromosome in the somatic cells of females. This phenomenon is common to both eutherian and marsupial mammals, but there are fundamental differences. In eutherians, the X chosen for silencing is random. DNA methylation on the eutherian inactive X is high at transcription start sites (TSSs) and their flanking regions, resulting in universally high DNA methylation. This contrasts XCI in marsupials where the paternally derived X is always silenced, and in which DNA methylation is low at TSSs and flanking regions. Here, we examined the DNA methylation status of the tammar wallaby X chromosome during spermatogenesis to determine the DNA methylation profile of the paternal X prior to and at fertilization. Whole genome enzymatic methylation sequencing was carried out on enriched flow-sorted populations of premeiotic, meiotic, and postmeiotic cells. We observed that the X displayed a pattern of DNA methylation from spermatogonia to mature sperm that reflected the inactive X in female somatic tissue. Therefore, the paternal X chromosome arrives at the egg with a DNA methylation profile that reflects the transcriptionally silent X in adult female somatic tissue. We present this epigenetic signature as a candidate for the long sought-after imprint for paternal XCI in marsupials.

Using electrodermal activity to estimate fear learning differences in anxiety: A multiverse analysis.

Meta-analyses indicate differences in Pavlovian fear responses between anxious and non-anxious individuals using electrodermal activity (EDA). Recent research, however, has cast doubt on whether these effects are robust to different analytic choices. Using the multiverse approach conceived by Steegen et al. (2016), we surveyed analytic choices typically implemented in clinical fear conditioning research by conducting 1240 analyses reflecting different choice permutations. Only 1.45% of our analyses produced theoretically congruent statistically significant effects, and the strength and direction of the estimated effects varied substantially across EDA processing methods. We conclude that EDA-estimated fear learning differences are vulnerable to researcher degrees of freedom and make recommendations regarding which analytical choices should be approached with a high degree of caution.

Community-Engaged Implementation Strategies in Occupational Therapy: A Scoping Review.

IMPORTANCE:  Despite the potential of community-engaged implementation research (CEIR) in developing strategies to accelerate the translation of evidence-based interventions (EBIs), there is a noticeable knowledge gap in the current state of CEIR in occupational therapy. A synthesis of the concept, purpose, and operationalization of CEIR is necessary. OBJECTIVE:  To identify the contexts, purposes, and operationalization of CEIR, focusing on implementation strategies in occupational therapy. DATA SOURCES:  PubMed/MEDLINE, Embase, CINAHL, Scopus, and Web of Science. STUDY SELECTION AND DATA COLLECTION:  We included studies that were explicit and intentional about CEIR and that focused on implementation strategies to support the translation of occupational therapy interventions, clinical guidelines, practice models, theories, or assessments. We extracted the research context (e.g., partners, recruitment), purpose (e.g., why community-engaged research was used), and operationalization (e.g., community engagement [CE] activities, how their findings inform the research) using thematic analysis. FINDINGS:  Of 3,219 records, 6 studies were included. Involved partners were mainly occupational therapy practitioners from existing networks. CEIR that focuses on implementation strategies informs various aspects of research design, ranging from study design to sustainability, by developing community-academia partnerships, building implementation capacity, and creating implementation strategies across diverse research areas. Current research has used various but mostly traditional CE activities (e.g., focus groups). CONCLUSIONS AND RELEVANCE:  We synthesized evidence on CEIR focused on implementation strategies in occupational therapy. Intentional efforts are needed to collaborate with diverse partners, explore innovative CE activities, produce equitable outputs, and develop multilevel implementation strategies to accelerate the translation of EBIs into practice. Plain-Language Summary: In this review, we synthesize evidence on the contexts, purposes, and operationalization of community-engaged implementation research (CEIR), focusing on implementation strategies in occupational therapy research. We found that current implementation efforts mainly rely on occupational therapy practitioners as community partners and use traditional recruitment methods and community engagement activities. In turn, they develop implementation strategies that mainly target practitioners without comprehensive, multilevel implementation support. We suggest more equitable collaboration with diverse partners to effectively promote the implementation and dissemination of evidence-based interventions in occupational therapy practice.

Understanding Negative and Positive Feelings About Telerehabilitation in People With Chronic Knee Pain: A Mixed-Methods Study.

OBJECTIVES: To explore (1) initial feelings of people with knee osteoarthritis who are unexpectedly offered telerehabilitation, and (2) if their experiences met their expectations, and their willingness to use telerehabilitation in the future. DESIGN: Mixed-methods study of 122 people with knee osteoarthritis who were randomized to receive physiotherapist-delivered telerehabilitation in a clinical trial. METHODS: At enrollment in the trial, participants were unaware care would be delivered via telerehabilitation. At completion, quantitative (Likert scales, analyzed descriptively) and qualitative (open-text, underwent content/thematic analysis) questions asked participants about their initial feelings when randomized to telerehabilitation, if experiences met expectations, and willingness to use telerehabilitation in the future. RESULTS: Data were collected between October 2021 to March 2023. At enrollment, 44 (36% of 122) participants initially felt negative toward telerehabilitation (doubts about effectiveness, physiotherapist can't see/touch, believe in-person is better, can't communicate effectively, not good with technology), 18 (15%) were neutral, and 60 (49%) felt positive. After experiencing telerehabilitation, 43 (72%) people who were initially positive and 27 (61%) who were initially negative believed telerehabilitation exceeded their expectations (easier than expected, surprised by benefits/effectiveness, strong rapport with physiotherapist, convenience). Twenty-eight (23% of 122) people were not at all or slightly willing to use telerehabilitation in future (prefer hands-on, doesn't allow adequate assessment/observation, prefer in-person, don't like telerehabilitation). CONCLUSION: One in 2 people were positive about telerehabilitation from the outset, and 6 in 10 people who initially felt negative about telerehabilitation found that their experiences were better than expected. One in 4 people were unwilling to use telerehabilitation in the future, even after they had experienced it. J Orthop Sports Phys Ther 2024;54(9):1-14. Epub 11 June 2024. doi:10.2519/jospt.2024.12383.

The control group matters: Pain, physical function and strength improvements relative to the comparator intervention in knee and hip osteoarthritis.

BACKGROUND: In knee and hip osteoarthritis (OA), the mechanism for resistance exercise improving clinical outcomes and the dose-response between strength and clinical outcomes are unknown; in part due to inconsistent trial designs across studies. PURPOSE: To determine whether the effects of resistance exercise interventions on pain and function differ based on comparator group; and whether there is an association between improvements in lower extremity strength with improvements in pain and function in knee and hip OA. METHODS: We searched 6 databases (inception to January 28 2023,) for randomized controlled trials (RCTs) comparing land-based, resistance exercise-only interventions with no intervention or any other intervention. There were four subgroups for comparator intervention: NONE (none/placebo/sham/usual care), EXE (other exercise interventions alone), NONEXE (non-exercise interventions alone), COMBO (combined exercise + non-exercise interventions). The between-group effect (ES) was calculated for immediate post-intervention pain and function (activities of daily living (ADL) and sports/recreation (SPORT)). Meta-regression analyses were completed to evaluate the association between improvements in lower extremity strength (independent variable) and improvements in pain, ADL and SPORT (dependent variables), irrespective of comparator intervention. RESULTS: For knee OA (257 studies), there were large benefits for pain [ES (95 % CI) = -0.92 (-1.15, -0.69)], ADL [-0.79 (-1.01, -0.56)] and SPORT [-0.79 (-1.02, -0.56)] favouring resistance exercise interventions compared to NONE. For knee pain, there was also a moderate benefit favouring COMBO interventions compared to resistance exercise interventions [0.44 (0.23, 0.65)]. For hip OA (15 studies), there were moderate benefits for pain [-0.51 (-0.68, -0.33)], ADL [-0.57 (-0.78, -0.36)] and SPORT [-0.52 (-0.70, -0.35)] favouring exercise interventions compared to NONE. For hip pain, there was also a moderate benefit favouring NONEXE interventions compared to resistance exercise interventions [0.57 (0.17, 0.97)]. For knee OA, greater strength gains were associated with larger improvements in pain [ß (95 % CI) = -0.24 (-0.38, -0.09)], ADL [-0.43 (-0.73, -0.12)] and SPORT [-0.37 (-0.73, -0.00)]. CONCLUSION: In knee and hip OA, the effects of resistance exercise on pain and function improvements depend on the comparator intervention. For knee OA, a dose-response relationship was observed between lower extremity strength gains with pain and function improvements.

Incomplete transcriptional dosage compensation of chicken and platypus sex chromosomes is balanced by post-transcriptional compensation.

Heteromorphic sex chromosomes (XY or ZW) present problems of gene dosage imbalance between sexes and with autosomes. A need for dosage compensation has long been thought to be critical in vertebrates. However, this was questioned by findings of unequal mRNA abundance measurements in monotreme mammals and birds. Here, we demonstrate unbalanced mRNA levels of X genes in platypus males and females and a correlation with differential loading of histone modifications. We also observed unbalanced transcripts of Z genes in chicken. Surprisingly, however, we found that protein abundance ratios were 1:1 between the sexes in both species, indicating a post-transcriptional layer of dosage compensation. We conclude that sex chromosome output is maintained in chicken and platypus (and perhaps many other non therian vertebrates) via a combination of transcriptional and post-transcriptional control, consistent with a critical importance of sex chromosome dosage compensation.

Exploring Experiences of People With Knee Osteoarthritis Who Received a Physiotherapist-Delivered Dietary Weight Loss and Exercise Intervention: A Mixed Methods Study.

OBJECTIVE: Explore the experiences of people with knee osteoarthritis (OA) who received a very low energy diet (VLED) and exercise program from a physiotherapist. METHODS: Mixed methods study involving questionnaires (n = 42) and semistructured interviews (n = 22) with randomized control trial participants with knee OA who had received a 6-month physiotherapist-delivered VLED weight loss and exercise intervention. Questionnaires measured participant satisfaction and perceptions about physiotherapist's skills/knowledge in delivery of the dietary intervention (measured on 5-7 point Likert scales). Interviews explored participant's experiences and were analyzed based on the principles of reflexive thematic analysis. RESULTS: Questionnaire response: 90%. Participants were satisfied with the program (95%), confident their physiotherapist had the required skills (84%) and knowledge (79%) to deliver the dietary intervention, felt comfortable talking to the physiotherapist about weight (74%), and would recommend others see a physiotherapist for the intervention they undertook (71%). The following four themes were developed from the interviews: (1) one-stop-shop of exercise and diet; (2) physiotherapist-delivered weight loss works (unsure initially; successfully lost weight); (3) physiotherapists knowledge and skills (exercise is forte; most thought physiotherapists had the necessary weight loss skills/knowledge, but some disagreed); and (4) physiotherapists have a role in weight loss (physiotherapists are intelligent, credible, and trustworthy; specific training in weight loss necessary). CONCLUSION: This study provides, to our knowledge, the first documented perspectives from people with OA who have received a physiotherapist-delivered weight loss intervention. Findings suggest physiotherapists may have a role in delivering a protocolized dietary intervention for some people with knee OA with overweight and obesity.

Training physicians in motivational communication: An integrated knowledge transfer study protocol.

OBJECTIVE: While behavior change counseling (BCC) targeting health risk behaviors has shown efficacy for improving patient health outcomes, barriers to knowledge translation have resulted in poor uptake among health care providers (HCPs). This article outlines the development of a new BCC training framework for HCPs, from inception to readiness for efficacy testing. It provides an example of integrated knowledge translation (iKT) used in alignment with the obesity-related behavioral intervention trials model. METHOD: (a) A modified Delphi process identified essential BCC skills for HCPs; (b) a survey assessed HCP attitudes and training needs; (c) an online competency assessment tool was developed using iKT mixed methods; (d) a training program was developed and refined using a logic model; and (e) the program was optimized using iterative rounds of participant feedback. A future proof-of-concept trial (f) will determine the program's readiness for full efficacy testing. RESULTS: A Delphi panel (n = 46) identified 11 core BCC competencies for HCPs, defining "motivational communication." The HCP survey (n = 80) showed willingness to devote 4 hr to introductory training in BCC. The Motivational Communication Competency Assessment Test (MC-CAT: an online, interactive evaluation tool) and a motivational communication training program (MOTIVATOR: accredited for continuing education by the Royal College of Physicians and Surgeons of Canada) were collaboratively developed with knowledge users. The optimization process (n = 11) provided key feedback, with minor changes being made to the program. CONCLUSIONS: In developing a new BCC framework, obstacles to BCC implementation were addressed through an iterative iKT process. This should improve eventual intervention uptake. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

An educational approach to develop intercultural nursing care for refugees from Ukraine: A qualitative study.

AIM: To describe how nurses and nursing students in Poland and the United States perceive the practice of intercultural care of refugees from Ukraine. BACKGROUND: Millions of Ukrainian citizens sought safety in other countries when Russia invaded Ukraine in February 2022. INTRODUCTION: Nurses in Poland and the United States are positioned to provide nursing care for refugees from Ukraine yet lack intercultural knowledge, skills, and attitudes to meet refugee needs. METHODS: This education-focused qualitative description study was conducted in Spring 2023. Eighteen MSN and BSN students from one university in Poland and one university in the United States completed an international virtual exchange course that concentrated on the health and well-being of refugees from Ukraine. Students' reflection papers generated the data for this study. Content analysis was used to systematically structure the data, and themes were inductively derived for an initial understanding of intercultural care for refugees. The COREQ guidelines were followed for reporting study findings. RESULTS: Major themes were troubled communication, overlooked trauma-informed care, and compromised vaccine status. Language differences, a gap in nursing knowledge, and cultural variations impeded intercultural care. DISCUSSION: To address intercultural care for refugees from Ukraine, macro- and microlevel factors should be considered. Healthcare facilities need certified interpreters or adequate language-access technology for nurses. Nursing programs might evaluate content on trauma-informed care and cultural competency to meet the needs of war-affected refugees. Leaders from Ukrainian refugee communities could partner with nurses to deliver culturally relevant information to increase vaccine uptake. IMPLICATIONS: Nurses should advocate for inclusion of the WHO competency standards of care for refugees in healthcare policies with emphasis on communication and evidence-informed practice. Placing Ukrainian community leaders on health councils could bridge the gap between refugees and mainstream society.