Elevated homocysteine is associated with increased rates of epigenetic aging in a population with mild cognitive impairment.

Elevated plasma total homocysteine (tHcy) is associated with the development of Alzheimer's disease and other forms of dementia. In this study, we report the relationship between tHcy and epigenetic age in older adults with mild cognitive impairment from the VITACOG study. Epigenetic age and rate of aging (ROA) were assessed using various epigenetic clocks, including those developed by Horvath and Hannum, DNAmPhenoAge, and with a focus on Index, a new principal component-based epigenetic clock that, like DNAmPhenoAge, is trained to predict an individual's "PhenoAge." We identified significant associations between tHcy levels and ROA, suggesting that hyperhomocysteinemic individuals were aging at a faster rate. Moreover, Index revealed a normalization of accelerated epigenetic aging in these individuals following treatment with tHcy-lowering B-vitamins. Our results indicate that elevated tHcy is a risk factor for accelerated epigenetic aging, and this can be ameliorated with B-vitamins. These findings have broad relevance for the sizable proportion of the worldwide population with elevated tHcy.

Disrupting the Family Stress-Proximal Process: A Scoping Review of Interventions for Children with Incarcerated Parents.

The United States' overreliance on incarceration has resulted in the imprisonment of millions of individuals - the majority of whom are parents of minor children. While mass incarceration has failed to effectively reduce crime or increase safety, it has dramatically harmed children and families in the United States. In turn, a wealth of research confirms the negative social, emotional, and psychological impacts of parental incarceration on children and the disproportionate impact on Black and Hispanic families and families living in poverty. As activists work towards dismantling this discriminatory and overly punitive system, it is also necessary to support children and adolescents currently impacted by parental incarceration. Using the Family Stress-Proximal Process (FSPP) model (Arditti, 2016) as a frame, the current paper critically reviews the literature on interventions to support children with incarcerated parents (CIP). The use of the FSPP frame highlights that while most intervention research has focused on promoting parenting skills of incarcerated parents and improving visit experiences, there is a dearth of research on interventions that 1) support at-home caregivers, 2) provide developmentally-targeted and -appropriate services and 3) acknowledge and counteract systems of inequality like structural racism and poverty that cause and exacerbate incarceration-related stress. These findings support a research agenda that prioritizes interventions framed around the intersectional identities of CIP and the intersecting systems that impact their lives.

The Burden of Work Productivity and Activity Impairment in Patients with Psoriasis, Psoriatic Arthritis, Ulcerative Colitis, and Crohn's Disease.

BACKGROUND: Comparisons among autoimmune diseases enable understanding of the burden and factors associated with work productivity loss and impairment. AIMS: The objective was to compare work productivity and activity and associated factors among patients with inflammatory bowel diseases and other autoimmune conditions. METHODS: This cross-sectional study included employed, adult patients (age 20-64 years) in the CorEvitas Inflammatory Bowel Disease, Psoriasis, and Psoriatic Arthritis/Spondyloarthritis Registries between 5/2017 and 6/2020. Any patient-reported impairment on four domains of the Work Productivity and Activity Index (WPAI) was collected across registries. Prevalence for each autoimmune disease was reported and stratified by disease activity using direct age-sex-standardization. Factors associated with the presence of any WPAI were identified in logistic regression models. RESULTS: A total of 7,169 patients with psoriasis (n = 4,768, 67%), psoriatic arthritis (n = 1,208, 17%), Crohn's disease (CD, n = 621, 9%), and ulcerative colitis (UC, n = 572, 8%) met inclusion criteria. Among patients not in remission across all disease cohorts, the age-sex-standardized prevalence of any presenteeism, work productivity loss, and activity impairment ranged from 54 to 97%. Patients with CD in remission had higher standardized prevalence of presenteeism (53% [48-57%]) and work productivity loss (54% [49-59%]), compared to those from other cohorts (presenteeism [range: 33-39%] and work productivity loss [range: 37-41%]). For all WPAI domains, the strongest adjusted associations were for moderate to severe disease activity and psychosocial symptoms. CONCLUSIONS: Patients with moderate to severe disease activity reported the highest WPAI burden. However, patients in remission or mild disease activity also report some WPAI burden, emphasizing a multidisciplinary treatment approach to improve work productivity loss and impairment.

CO2 exposure drives a rapid pH response in live adult Drosophila.

CO2 anesthesia is the most common method for immobilizing Drosophila for research purposes. But CO2 exposure has consequences-it can impact fertility, behavior, morphogenesis, and cytoskeletal dynamics. In this respect, Drosophila is an outstanding model for studying the impact of CO2 exposure on tissues. In this study we explored the response of intracellular pH (pHi) to a one-minute CO2 pulse using a genetically encoded, ubiquitously expressed pH sensor, tpHusion, to monitor pHi within a live, intact, whole fly. We compared wild-type flies to flies lacking Imaginal disc growth factors (Idgfs), which are chitinase-like proteins that facilitate developmental processes and the innate immune response. Morphogenetic and cytoskeletal defects in Idgf-null flies are enhanced after CO2 exposure. We found that pHi drops sharply within seconds of the beginning of a CO2 pulse and recovers over several minutes. The initial profile was nearly identical in control and Idgf-null flies but diverged as the pHi returned to normal. This study demonstrates the feasibility of monitoring pH in live adult Drosophila. Studies exploring pH homeostasis are important for understanding human pathologies associated with pH dysregulation.

A multimodal precision-prevention approach combining lifestyle intervention with metformin repurposing to prevent cognitive impairment and disability: the MET-FINGER randomised controlled trial protocol.

BACKGROUND: Combining multimodal lifestyle interventions and disease-modifying drugs (novel or repurposed) could provide novel precision approaches to prevent cognitive impairment. Metformin is a promising candidate in view of the well-established link between type 2 diabetes (T2D) and Alzheimer's Disease and emerging evidence of its potential neuro-protective effects (e.g. vascular, metabolic, anti-senescence). MET-FINGER aims to test a FINGER 2.0 multimodal intervention, combining an updated FINGER multidomain lifestyle intervention with metformin, where appropriate, in an APOE ε4-enriched population of older adults (60-79 years) at increased risk of dementia. METHODS: MET-FINGER is an international randomised, controlled, parallel-group, phase-IIb proof-of-concept clinical trial, where metformin is included through a trial-within-trial design. 600 participants will be recruited at three sites (UK, Finland, Sweden). Participants at increased risk of dementia based on vascular risk factors and cognitive screening, will be first randomised to the FINGER 2.0 intervention (lifestyle + metformin if eligible; active arm) or to receive regular health advice (control arm). Participants allocated to the FINGER 2.0 intervention group at risk indicators of T2D will be additionally randomised to receive metformin (2000 mg/day or 1000 mg/day) or placebo. The study duration is 2 years. The changes in global cognition (primary outcome, using a Neuropsychological Test Battery), memory, executive function, and processing speed cognitive domains; functional status; lifestyle, vascular, metabolic, and other dementia-related risk factors (secondary outcomes), will be compared between the FINGER 2.0 intervention and the control arm. The feasibility, potential interaction (between-groups differences in healthy lifestyle changes), and disease-modifying effects of the lifestyle-metformin combination will be exploratory outcomes. The lifestyle intervention is adapted from the original FINGER trial (diet, physical activity, cognitive training, monitoring of cardiovascular/metabolic risk factors, social interaction) to be consistently delivered in three countries. Metformin is administered as Glucophage®XR/SR 500, (500 mg oral tablets). The metformin/placebo treatment will be double blinded. CONCLUSION: MET-FINGER is the first trial combining a multimodal lifestyle intervention with a putative repurposed disease-modifying drug for cognitive impairment prevention. Although preliminary, its findings will provide crucial information for innovative precision prevention strategies and form the basis for a larger phase-III trial design and future research in this field. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05109169).

Flexible approaches to eCOA administration in clinical trials: The site perspective.

The Critical Path Institute convened the Support Flexible Approaches to PRO Data Collection project as part of the eCOA: Getting Better Together Initiative which was instigated to identify and address common challenges and drive positive change with eCOA implementation in clinical trials. The project aimed to identify clinical trial stakeholders' concerns related to electronic PRO (ePRO) implementation and propose areas of improvement via simplification and flexibility. One workstream focused on patient-/site-centric approaches for simplification and surveyed representatives of clinical sites and site monitors for their perspectives. A semi-structured questionnaire was developed and distributed via snowball sampling to site professionals and clinical research associates (CRAs) that had ePRO experience who had been identified via representative groups or sponsor-led site networks. Responses were received from various site roles across a range of global regions; the largest contribution was from the United States. Topics raised included helpdesk capabilities, technical concerns, device types, and user interfaces among others and are discussed further in this paper. The feedback derived from the questionnaire provided the basis for concrete ideas that sponsors should consider incorporating into protocol design for participant visits, technology use, devices, and methods of back-up data collection.

Factors in Hand Surgery Access for Rheumatoid Arthritis Before vs After the Patient Protection and Affordable Care Act.

Importance: Rheumatoid arthritis (RA) has severe functional and economic consequences. The implications of the Patient Protection and Affordable Care Act (ACA) and demographic factors for access to surgical treatment are unclear. Objective: To investigate factors associated with time to RA hand surgery, surgical incidence, and cost after implementation of the ACA. Design, Setting, and Participants: This cross-sectional study used insurance data from the IBM MarketScan Research Databases from 2009 through 2020 to compare time to surgery, surgical incidence, and treatment cost for RA of the hand before and after ACA implementations. Included patients were 18 years or older with a new diagnosis for RA of the hand and at least 1 procedural code for arthroplasty, arthrodesis, tenolysis, tendon repair, or tendon transfer. Patients with coexisting inflammatory arthritis diagnoses were excluded. Demographic variables analyzed included patient sex, age at index date, residence within or outside a metropolitan statistical area (MSA; hereafter urban or nonurban), insurance and health plan type, Social Deprivation Index, Elixhauser Comorbidity Index score, and Rheumatic Disease Comorbidity Index. Data analysis occurred from October 2022 to April 2023. Exposures: Surgery for RA of the hand during the pre-ACA (before 2014) vs post-ACA (2014 or later) periods. Main Outcomes and Measures: Time to surgery, surgical incidence, and cost of treating RA in patients undergoing hand surgery for RA. Results: Among 3643 patients (mean [SD] age, 57.6 [12.3] years) who underwent hand surgery for RA, 3046 (83.6%) were women. Post-ACA passage, 595 (86.2%) patients who resided in urban areas had a significantly lower time to surgery than those who did not (-70.5 [95% CI, -112.6 to -28.3] days; P < .001). Among urban patients, the least socially disadvantaged patients experienced the greatest decrease in time to surgery after ACA but the change was not statistically significant. For all patients, greater social disadvantage (ie, a higher SDI score) was associated with a longer time to surgery in the post-ACA period; for example, compared with the least socially disadvantaged group (SDI decile, 0-10), patients in SDI decile 10 to 20 waited an additional 254.0 days (95% CI, 65.2 to 442.9 days; P = .009) before undergoing surgery. Compared with the pre-ACA period, the mean surgical incidence in the post-ACA period was 83.4% lower (162.3 vs 26.9 surgeries per 1000 person-years; P < .001), and surgical incidence was 86.3% lower in nonurban populations (27.2 vs 3.7 surgeries per 1000 person-years; P < .001) but only 82.8% lower in urban populations (135.1 vs 23.2 surgeries per 1000 person-years; P < .001). Per capita total costs of all treatment related to RA of the hand decreased in the post-ACA period but the change was not statistically significant. Insurer-paid costs were lower in the post-ACA period but the change was not statistically significant. Out-of-pocket expenses did not change. Conclusions and Relevance: Findings of this cross-sectional study suggest that after ACA passage, disparities exist in access to timely, cost-effective hand surgery for RA. Increased access to surgical hand specialists is needed for nonurban residents and those with greater social deprivation, along with insurance policy reforms to further decrease out-of-pocket spending for RA hand surgery.

Best Practices for the Electronic Implementation and Migration of Patient-Reported Outcome Measures.

While the use of electronic methods to collect patient-reported outcome data in clinical trials continues to increase, it remains the case that many patient-reported outcome measures (PROMs) have originally been developed and validated on paper. Careful consideration during the move from paper PROMs to electronic format is required to preserve the integrity of the measure and ensure a "faithful migration." Relevant literature has long called out the importance of following migration best practices during this process; nevertheless, such best practices are distributed across multiple documents. This article consolidates and builds upon existing electronic PROM implementation best practice recommendations to provide a comprehensive, up-to-date, single point of reference. It reflects the current consensus based on the significant advances in technology capabilities and knowledge gleaned from the growing evidence base on electronic migration and implementation, to balance the need for maintaining the integrity of the measure while optimizing respondent usability. It also specifies whether the practice is rooted in evidence or expert consensus, to enable those using these best practices to make informed and considered decisions when conducting migration.

Professor Dr Hendrik (Henk) Schenk (1939-2023).

Obituary for Professor Dr Hendrik (Henk) Schenk.

[Self-perception of smoking cessation skills among Cardiology residents in Argentina]. / Autopercepción de las habilidades para la cesación del tabaquismo entre los residentes de cardiología en Argentina.

Objective: To evaluate the self-perception of cardiology residents in Argentina regarding their abilities to help their patients stop smoking, as well as their opinions about their knowledge and skills in this area. Materials and methods: A cross-sectional study was carried out using secondary data from a study carried out in five Latin American countries and Spain, focusing on the information provided by cardiology residents in Argentina. Discrete variables were expressed as median and interquartile range, and categorical variables were expressed as percentages, and were analyzed using the chi-square test or Fisher's exact test, depending on the relative frequency of the expected values. Results: 447 residents participated; 87.5% routinely provided brief advice to quit smoking, and 11.6% used validated questionnaires to assess the degree of addiction. Furthermore, 32.1% stated that they prescribed pharmacological treatment, but 53.1% were only familiar with a single drug. When asked about their self-perception of getting their patients to stop smoking, the median response was 5 (scale from 1 to 10); only 13.7% responded with a score of 8 or more. Conclusions: The present study suggests that cardiology residents in Argentina recognize the importance of carrying out smoking cessation interventions, but a high proportion of them do not feel qualified to do so.

Standardized Order Sets Do Not Eliminate Racial or Ethnic Inequities in Postpartum Pain Management.

Objective: To quantify the extent to which a standardized pain management order set reduced racial and ethnic inequities in post-cesarean pain evaluation and management. Methods: We conducted a retrospective cohort study to quantify racial and ethnic differences in pain evaluation and management before (July 2014-June 2016) and after implementation of a standardized post-cesarean order set (March 2017-February 2018). Electronic medical records were queried for pain scores >7/10, number of pain assessments, and opioid, nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen doses. Outcomes were grouped into 0 to <24 and 24-48 h postpartum, and stratified by race/ethnicity (Hispanic, non-Hispanic Black [NHB], non-Hispanic White [NHW], Asian, and other), as documented in the electronic health record. Analyses included logistic regression for the categorical outcome of pain score >7 (severe pain), and linear regression, with propensity score adjustment. Main effect and interaction terms were used to calculate the difference-in-difference in pain process and outcome measures between the baseline and follow-up periods. Results: After order set implementation (N=888), severe pain remained more common among NHB patients (% pain scores >7 NHW vs. NHB 0 to <24 h: 22% vs. 33%, p=0.003; 24-48 h: 26% vs. 40%, p<0.001). Among all patients, pain management processes changed after implementation of the order set, with overall fewer assessments, less Opioids, and more nonopioid analgesics. However, racial and ethnic inequities in a number of assessments and in treatment were unchanged (all p for interaction >0.05), with the exception of a modest increase in NSAID doses 24-48 h postpartum for Hispanic patients. Conclusion: A standardized pain management order set reduced overall postpartum opioid use, but did not reduce racial and ethnic disparities in pain evaluation and management. Future work should investigate racial equity-focused education and interventions designed to eliminate disparities in pain management.

Boosting of vaginal HSV-2-specific B and T cell responses by intravaginal therapeutic immunization results in diminished recurrent HSV-2 disease.

Boosting herpes simplex virus (HSV)-specific immunity in the genital tissues of HSV-positive individuals to increase control of HSV-2 recurrent disease and virus shedding is an important goal of therapeutic immunization and would impact HSV-2 transmission. Experimental therapeutic HSV-2 vaccines delivered by a parenteral route have resulted in decreased recurrent disease in experimental animals. We used a guinea pig model of HSV-2 infection to test if HSV-specific antibody and cell-mediated responses in the vaginal mucosa would be more effectively increased by intravaginal (Ivag) therapeutic immunization compared to parenteral immunization. Therapeutic immunization with HSV glycoproteins and CpG adjuvant increased glycoprotein-specific IgG titers in vaginal secretions and serum to comparable levels in Ivag- and intramuscular (IM)-immunized animals. However, the mean numbers of HSV glycoprotein-specific antibody secreting cells (ASCs) and IFN-γ SCs were greater in Ivag-immunized animals demonstrating superior boosting of immunity in the vaginal mucosa compared to parenteral immunization. Therapeutic Ivag immunization also resulted in a significant decrease in the cumulative mean lesion days compared to IM immunization. There was no difference in the incidence or magnitude of HSV-2 shedding in either therapeutic immunization group compared to control-treated animals. Collectively, these data demonstrated that Ivag therapeutic immunization was superior compared to parenteral immunization to boost HSV-2 antigen-specific ASC and IFN-γ SC responses in the vagina and control recurrent HSV-2 disease. These results suggest that novel antigen delivery methods providing controlled release of optimized antigen/adjuvant combinations in the vaginal mucosa would be an effective approach for therapeutic HSV vaccines. IMPORTANCE HSV-2 replicates in skin cells before it infects sensory nerve cells where it establishes a lifelong but mostly silent infection. HSV-2 occasionally reactivates, producing new virus which is released back at the skin surface and may be transmitted to new individuals. Some HSV-specific immune cells reside at the skin site of the HSV-2 infection that can quickly activate and clear new virus. Immunizing people already infected with HSV-2 to boost their skin-resident immune cells and rapidly control the new HSV-2 infection is logical, but we do not know the best way to administer the vaccine to achieve this goal. In this study, a therapeutic vaccine given intravaginally resulted in significantly better protection against HSV-2 disease than immunization with the same vaccine by a conventional route. Immunization by the intravaginal route resulted in greater stimulation of vaginal-resident, virus-specific cells that produced antibody and produced immune molecules to rapidly clear virus.

The impacts of social restrictions during the COVID-19 pandemic on the physical activity levels of over 50-year olds: The CHARIOT COVID-19 Rapid Response (CCRR) cohort study.

OBJECTIVES: To quantify the associations between shielding status and loneliness at the start of the COVID-19 pandemic, and physical activity (PA) levels throughout the pandemic. METHODS: Demographic, health and lifestyle characteristics of 7748 cognitively healthy adults aged >50, and living in London, were surveyed from April 2020 to March 2021. The International Physical Activity Questionnaire (IPAQ) short-form assessed PA before COVID-19 restrictions, and up to 6 times over 11 months. Linear mixed models investigated associations between shielding status and loneliness at the onset of the pandemic, with PA over time. RESULTS: Participants who felt 'often lonely' at the outset of the pandemic completed an average of 522 and 547 fewer Metabolic Equivalent of Task (MET) minutes/week during the pandemic (95% CI: -809, -236, p<0.001) (95% CI: -818, -275, p<0.001) than those who felt 'never lonely' in univariable and multivariable models adjusted for demographic factors respectively. Those who felt 'sometimes lonely' completed 112 fewer MET minutes/week (95% CI: -219, -5, p = 0.041) than those who felt 'never lonely' following adjustment for demographic factors. Participants who were shielding at the outset of the pandemic completed an average of 352 fewer MET minutes/week during the pandemic than those who were not (95% CI: -432, -273; p<0.001) in univariable models and 228 fewer MET minutes/week (95% CI: -307, -150, p<0.001) following adjustment for demographic factors. No significant associations were found after further adjustment for health and lifestyle factors. CONCLUSIONS: Those shielding or lonely at pandemic onset were likely to have completed low levels of PA during the pandemic. These associations are influenced by co-morbidities and health status.

Omics-Based Investigations of Breast Cancer.

Breast cancer (BC) is characterized by an extensive genotypic and phenotypic heterogeneity. In-depth investigations into the molecular bases of BC phenotypes, carcinogenesis, progression, and metastasis are necessary for accurate diagnoses, prognoses, and therapy assessments in predictive, precision, and personalized oncology. This review discusses both classic as well as several novel omics fields that are involved or should be used in modern BC investigations, which may be integrated as a holistic term, onco-breastomics. Rapid and recent advances in molecular profiling strategies and analytical techniques based on high-throughput sequencing and mass spectrometry (MS) development have generated large-scale multi-omics datasets, mainly emerging from the three "big omics", based on the central dogma of molecular biology: genomics, transcriptomics, and proteomics. Metabolomics-based approaches also reflect the dynamic response of BC cells to genetic modifications. Interactomics promotes a holistic view in BC research by constructing and characterizing protein-protein interaction (PPI) networks that provide a novel hypothesis for the pathophysiological processes involved in BC progression and subtyping. The emergence of new omics- and epiomics-based multidimensional approaches provide opportunities to gain insights into BC heterogeneity and its underlying mechanisms. The three main epiomics fields (epigenomics, epitranscriptomics, and epiproteomics) are focused on the epigenetic DNA changes, RNAs modifications, and posttranslational modifications (PTMs) affecting protein functions for an in-depth understanding of cancer cell proliferation, migration, and invasion. Novel omics fields, such as epichaperomics or epimetabolomics, could investigate the modifications in the interactome induced by stressors and provide PPI changes, as well as in metabolites, as drivers of BC-causing phenotypes. Over the last years, several proteomics-derived omics, such as matrisomics, exosomics, secretomics, kinomics, phosphoproteomics, or immunomics, provided valuable data for a deep understanding of dysregulated pathways in BC cells and their tumor microenvironment (TME) or tumor immune microenvironment (TIMW). Most of these omics datasets are still assessed individually using distinct approches and do not generate the desired and expected global-integrative knowledge with applications in clinical diagnostics. However, several hyphenated omics approaches, such as proteo-genomics, proteo-transcriptomics, and phosphoproteomics-exosomics are useful for the identification of putative BC biomarkers and therapeutic targets. To develop non-invasive diagnostic tests and to discover new biomarkers for BC, classic and novel omics-based strategies allow for significant advances in blood/plasma-based omics. Salivaomics, urinomics, and milkomics appear as integrative omics that may develop a high potential for early and non-invasive diagnoses in BC. Thus, the analysis of the tumor circulome is considered a novel frontier in liquid biopsy. Omics-based investigations have applications in BC modeling, as well as accurate BC classification and subtype characterization. The future in omics-based investigations of BC may be also focused on multi-omics single-cell analyses.

Kinetic and Kinematic Assessment of the Band-Assisted Countermovement Jump.

ABSTRACT: Fernandes, JFT, Arede, J, Clarke, H, Garcia-Ramos, A, Perez-Castilla, A, Norris, JP, Wilkins, CA, and Dingley, AF. Kinetic and kinematic assessment of the band-assisted countermovement jump. J Strength Cond Res 37(8): 1588-1593, 2023-This study sought to elucidate kinetic and kinematic differences between unloaded and band-assisted countermovement jumps (CMJs). In a randomized order, 20 healthy subjects (mass 84.5 ± 18.6 kg) completed 3 repetitions of CMJs across 3 conditions: unloaded (at body mass), low, and moderate band (8.4 ± 1.9 and 13.3 ± 3.3 kg body mass reduction, respectively). For all repetitions, a force platform and linear position transducer were used to record and calculate kinetic and kinematic data. Body mass was significantly different between the unloaded, low, and moderate band conditions ( p < 0.05). Peak velocity, absolute peak, and mean force and movement duration displayed a trend that was mostly related to the condition (i.e., unloaded > low > moderate) ( p < 0.05). The opposing trend (i.e., moderate > low > unloaded) was generally observed for relative peak and mean force, reactive strength index modified, and flight time ( p < 0.05). No differences were observed for mean velocity, movement duration, and absolute and relative landing forces ( p > 0.05). The use of band assistance during CMJs can alter force, time, and velocity variables. Practitioners should be aware of the potential positive and negative effects of band assistance during CMJs.

Static pelvic posture is not related to dynamic pelvic tilt or competition level in dressage riders.

Static assessment and grouping of riders by competition level are prevalent in equestrian coaching practice and research. This study explored sagittal pelvic tilt in 35 competitive dressage riders to analyse the relationship between static and dynamic postures and assess the interaction of competition level. Riders were assessed using optical motion capture on a riding simulator at halt and in walk, trot, and left and right canter. Mean, minimum and maximum pelvic tilt, and range of motion (ROM) were measured as the pitch rotation of a rigid body formed by markers placed on the rider's left/right anterior and posterior superior iliac spines and sacrum, averaged over six time-normalised strides. Three key results emerged: (1) there are correlations between the rider's mean pelvic tilt in simulated walk, trot and canter, but not at halt; (2) mean pelvic tilt values are not significantly influenced by competition level (p = 0.233); and (3) the minimum and maximum pelvic tilt values illustrate individual strategies between gaits. Therefore, results from static assessment and grouping of riders by competition level should be interpreted with caution. Riders should be assessed as individuals, during dynamic riding-specific tasks, to understand their postural strategies.

Imaginal disk growth factors are Drosophila chitinase-like proteins with roles in morphogenesis and CO2 response.

Chitinase-like proteins (CLPs) are members of the family 18 glycosyl hydrolases, which include chitinases and the enzymatically inactive CLPs. A mutation in the enzyme's catalytic site, conserved in vertebrates and invertebrates, allowed CLPs to evolve independently with functions that do not require chitinase activity. CLPs normally function during inflammatory responses, wound healing, and host defense, but when they persist at excessive levels at sites of chronic inflammation and in tissue-remodeling disorders, they correlate positively with disease progression and poor prognosis. Little is known, however, about their physiological function. Drosophila melanogaster has 6 CLPs, termed Imaginal disk growth factors (Idgfs), encoded by Idgf1, Idgf2, Idgf3, Idgf4, Idgf5, and Idgf6. In this study, we developed tools to facilitate characterization of the physiological roles of the Idgfs by deleting each of the Idgf genes using the CRISPR/Cas9 system and assessing loss-of-function phenotypes. Using null lines, we showed that loss of function for all 6 Idgf proteins significantly lowers viability and fertility. We also showed that Idgfs play roles in epithelial morphogenesis, maintaining proper epithelial architecture and cell shape, regulating E-cadherin and cortical actin, and remarkably, protecting these tissues against CO2 exposure. Defining the normal molecular mechanisms of CLPs is a key to understanding how deviations tip the balance from a physiological to a pathological state.