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There has been an enormous increase in foster care placements, especially with grandparents and other extended family members, since 1985. This is primarily attributable to problems associated with parental drug use, principally of crack cocaine. Drug related problems that lead to kinship foster placement include prenatal drug exposure, child maltreatment, incarceration, and early death by violence or AIDS or other illness. Grandparents caring for their children's children have a variety of social, mental health, and medical needs because of this stressful role. Following a literature review, a comprehensive social service and medical program developed through the partnership of a large urban teaching hospital, a foundation involved in funding programs for older adults, and an inner city school district is described. [ABSTRACT FROM AUTHOR]

Skull stripping is a fundamental preprocessing step in modern neuroimaging analyses that consists of removing non-brain voxels from structural images. When performed entirely manually, this laborious step can be rate-limiting for analyses, with the potential to influence the population size chosen. This emphasizes the need for a fully- or semi-automated masking procedure to decrease man-hours without an associated decline in accuracy. These algorithms are plentiful in human neuroimaging but are relatively lacking for the plethora of animal species used in research. Unfortunately, software designed for humans cannot be easily transformed for animal use due to the high amount of tailoring required to accurately account for the considerable degree of variation within the highly folded human cortex. As most animals have a relatively less complex cerebral morphology, intersubject variability is consequently decreased, presenting the possibility to simply warp the brain mask of a template image into subject space for the purpose of skull stripping. This study presents the use of the Cat Automated Registration-based Skull Stripper (CARSS) tool on feline structural images. Validation metrics revealed that this method was able to perform on par with manual raters on >90 % of scans tested, and that its consistency across multiple runs was superior to that of masking performed by two independent raters. Additionally, CARSS outperformed three well-known skull stripping programs on the validation dataset. Despite a handful of manual interventions required, the presented tool reduced the man-hours required to skull strip 60 feline images over tenfold when compared to a fully manual approach, proving to be invaluable for feline neuroimaging studies, particularly those with large population sizes., Competing Interests: Declaration of competing interest There are no declarations of interest., (Copyright © 2024. Published by Elsevier Inc.)

In response to sensory deprivation, the brain adapts according to contemporary demands to efficiently navigate a modified perceptual environment. This reorganization may result in improved processing of the remaining senses-a phenomenon referred to as compensatory crossmodal plasticity. One approach to explore this neuroplasticity is to consider the macrostructural changes in neural tissue that mirror this functional optimization. The current study is the first of its kind to measure MRI-derived gray matter (GM) volumes of control felines (n=30), while additionally identifying volumetric differences in response to perinatal deafness (30 ototoxically-deafened cats). To accomplish this purpose, regional and morphometric methods were performed in parallel. The regional analysis evaluated volumetric alterations of global GM, as well as the volumes of 146 regions of interest (ROIs) and 12 functional subgroupings of these ROIs. Results revealed whole-brain GM preservation; however, somatosensory and visual cortices exhibited an overall increase in volume. On a smaller scale, this analysis uncovered two auditory ROIs (second auditory cortex, A2, and ventral auditory field, VAF) that decreased in volume alongside two visual regions (anteromedial lateral suprasylvian area, AMLS and splenial visual area, SVA) that increased-all localized within the right hemisphere. Comparatively, the findings of tensor-based morphometry (TBM) generally aligned with those of the ROI-based method, as this voxel-wise approach demonstrated clusters of expansion coincident with visual- and somatosensory-related loci; although, it failed to detect any GM reductions following deafness. As distinct differences were identified in each analysis, the current study highlights the importance of employing multiple methods when exploring MRI volumetry. Overall, this study proposes that volumetric alterations within sensory loci allude to a redistribution of cortical space arising from modified perceptual demands following auditory deprivation., Competing Interests: Declaration of competing interest There are no declarations of interest., (Copyright © 2024. Published by Elsevier Inc.)

During meiosis, the parental chromosomes are drawn together to enable exchange of genetic information. Chromosomes are aligned through the assembly of a conserved interface, the synaptonemal complex, composed of a central region that forms between two parallel chromosomal backbones called axes. Here we identify the axis-central region interface in C. elegans , containing a conserved positive patch on the axis component HIM-3 and the C-terminus of the central region protein SYP-5. Crucially, the canonical ultrastructure of the synaptonemal complex is altered upon weakening this interface. We developed a thermodynamic model that recapitulates our experimental observations, indicating that the liquid-like central region can assemble by wetting the axes without active energy consumption. More broadly, our data show that condensation drives tightly regulated nuclear reorganization during sexual reproduction., Competing Interests: Declaration of interests The authors declare no competing interests.

Background/purpose: Despite the prevalence of surgical intervention in seriously ill children, data is scarce regarding interventions performed based on type of serious illness. We therefore sought to evaluate the surgical interventions performed from the time of serious illness diagnosis to the present in a cohort of children receiving palliative care, including identification of the surgical specialists involved in these procedures., Methods: We conducted a retrospective cohort analysis of surgical interventions in 197 children enrolled in a multicenter prospective cohort study (Pediatric Palliative Care Research Network SHARE Study). All surgical interventions were abstracted via clinical record review., Results: 189 (of 197, 96%) patients (45% female) with an average of 5.3 complex, chronic conditions (CCC) underwent 3331 surgical interventions (median = 13) by 21 specialist teams (most commonly general surgeons). Those with hematologic malignancies underwent intervention most frequently, followed by children with respiratory, genetic/metabolic, and gastrointestinal/genitourinary (GI/GU) diagnoses. Children with cardiovascular disease, malignancies, and prematurity had the shortest time between diagnosis and first intervention and between diagnosis and pediatric palliative care (PPC) services. By contrast, those with genetic, neurologic, and respiratory diagnoses had significantly longer intervals between diagnosis and intervention., Conclusions: Nearly all seriously ill children receiving PPC undergo surgical intervention, and many undergo tens of interventions by a variety of subspecialist teams. Surgical intervention differs by serious illness type, with children with more acutely life-limiting illnesses undergoing high-volume, high-risk interventions in the immediate post-diagnosis period. Those with chronic, life-limiting illnesses undergo a higher lifetime volume of interventions that are relatively lower risk and more evenly distributed over time., Level of Evidence: N/A., Competing Interests: Conflicts of interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Following sensory deprivation, areas and networks in the brain may adapt and reorganize to compensate for the loss of input. These adaptations are manifestations of compensatory crossmodal plasticity, which has been documented in both human and animal models of deafness-including the domestic cat. Although there are abundant examples of structural plasticity in deaf felines from retrograde tracer-based studies, there is a lack of diffusion-based knowledge involving this model compared to the current breadth of human research. The purpose of this study was to explore white matter structural adaptations in the perinatally-deafened cat via tractography, increasing the methodological overlap between species. Plasticity was examined by identifying unique group connections and assessing altered connectional strength throughout the entirety of the brain. Results revealed a largely preserved connectome containing a limited number of group-specific or altered connections focused within and between sensory networks, which is generally corroborated by deaf feline anatomical tracer literature. Furthermore, five hubs of cortical plasticity and altered communication following perinatal deafness were observed. The limited differences found in the present study suggest that deafness-induced crossmodal plasticity is largely built upon intrinsic structural connections, with limited remodeling of underlying white matter., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction/objectives: Veterinary echocardiographers' preferences for left atrial (LA) size assessment in cats have not been systematically investigated. The primary aim of this prospective exploratory study was to investigate echocardiographers' preferences concerning LA size assessment in cats. A secondary aim was to investigate echocardiographers' preferences for assessing LA size in subgroups based on geographic, demographic, and professional profiles., Animals, Materials, and Methods: An online survey instrument was designed, verified, and distributed globally to veterinary echocardiographers., Results: A total of 655 veterinary echocardiographers from six continents and 54 countries, working in specialty practice (56%) and in general practice (38%), provided data. Linear two-dimensional (2D) technique was favored by most echocardiographers (n = 612) for LA size assessment. Most commonly, respondents combined linear 2D with subjective assessment (n = 227), while 209 used linear 2D-based methods alone. Most echocardiographers using linear 2D-based methods preferred the right parasternal short-axis view and to index the LA to the aorta (Ao). Approximately 10% of the respondents obtained LA dimensions from a right parasternal long-axis four-chamber view. Approximately one-third of echocardiographers that made linear measurements from 2D echocardiograms shared the same preferences regarding cat position, acquisition view, indexing method and time point identification for the LA measurement. The responses were comparably homogeneous across geographic location, level of training, years performing echocardiography, and type of practice., Discussion/conclusion: Most veterinary echocardiographers assessed LA size in cats using linear 2D echocardiography from a right parasternal short-axis view, and indexed LA to Ao. Respondents' preferences were similar over geographic, demographic, and professional backgrounds., Competing Interests: Conflict of Interest Statement The authors do not have any conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction/objectives: Veterinary echocardiographers' preferences for left atrial (LA) size assessment in dogs have never been systematically investigated. The primary aim of this international survey study was to investigate echocardiographers' preferences for LA size assessment in dogs. The secondary aim was to investigate echocardiographers' preferences for assessing LA size in subgroups based on geographic, demographic, and professional profiles., Animals, Materials, and Methods: An online survey instrument was designed, verified, and distributed globally to the veterinary echocardiographers., Results: A total of 670 echocardiographers from 54 countries on six continents completed the survey. Most echocardiographers (n = 621) used linear two-dimensional (2D)-based methods to assess LA size, 379 used subjective assessment, and 151 used M-mode-based methods. Most commonly, echocardiographers combined linear 2D-based methods with subjective assessment (n = 222), whereas 191 used linear 2D-based methods alone. Most echocardiographers (n = 436) using linear 2D-based methods preferred the right parasternal short-axis view and indexed the LA to the aorta. Approximately 30% (n = 191) of the echocardiographers who performed linear measurements from 2D echocardiograms shared the same preferences regarding dog position, acquisition view, indexing method, and identification of the time-point used for the measurement. The responses were comparably homogeneous across geographic location, training level, years of performing echocardiography, and type of practice., Discussion/conclusion: Most veterinary echocardiographers assessed LA size in dogs using linear 2D echocardiography from a right parasternal short-axis view, and by indexing the LA to the aorta. The respondents' preferences were similar across geographic, demographic, and professional backgrounds., Competing Interests: Conflict of Interest Statement The authors do not have any conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The transition from childhood to adolescence is associated with an increase in rates of some psychiatric disorders, including major depressive disorder, a debilitating mood disorder. The aim of this systematic review is to update the evidence on the benefits and harms of screening for depression in primary care and non-mental health clinic settings among children and adolescents., Methods: This review is an update of a previous systematic review, for which the last search was conducted in 2017. We searched Ovid MEDLINE® ALL, Embase Classic+Embase, PsycINFO, Cochrane Central Register of Controlled Trials, and CINAHL on November 4, 2019, and updated on February 19, 2021. If no randomized controlled trials were found, we planned to conduct an additional search for non-randomized trials with a comparator group. For non-randomized trials, we applied a non-randomized controlled trial filter and searched the same databases except for Cochrane Central Register of Controlled Trials from January 2015 to February 2021. We also conducted a targeted search of the gray literature for unpublished documents. Title and abstract, and full-text screening were completed independently by pairs of reviewers., Results: In this review update, we were unable to find any randomized controlled studies that satisfied our eligibility criteria and evaluated the potential benefits and harms of screening for depression in children and adolescents. Additionally, a search for non-randomized trials yielded no studies that met the inclusion criteria., Conclusions: The findings of this review indicate a lack of available evidence regarding the potential benefits and harms of screening for depression in children and adolescents. This absence of evidence emphasizes the necessity for well-conducted clinical trials to evaluate the effectiveness of depression screening among children and adolescents in primary care and non-mental health clinic settings., Systematic Review Registration: PROSPERO CRD42020150373 ., (© 2024. The Author(s).)

In a pre-registered survey linked to this paper (Exploring the relationships between psychological variables and loot box engagement, part 1: pre-registered hypotheses), we confirmed bivariate associations between engagement with loot boxes (purchasable randomized rewards in video games) and measures of problem gambling, problem video gaming, impulsivity, gambling cognitions, experiences of game-related 'flow', psychological distress and reduced wellbeing. However, these variables have complex relationships, so to gain further insights, we analysed the dataset (1495 gamers who purchase loot boxes and 1223 purchasers of non-randomized content) in a series of Bayesian mixed-effects multiple regressions with a zero-inflation component. The results challenge some well-established results in the literature, including associations between loot box engagement and problematic gambling measures, instead suggesting that this relationship might be underpinned by shared variance with problem video gaming and gambling-related cognitions. An entirely novel discovery revealed a complex interaction between experiences of flow and loot box engagement. Distress and wellbeing are both (somewhat contradictorily) predictive of participants engaging with loot boxes, but neither correlate with increasing loot box risky engagement/spend (among those who engage). Our findings unravel some of the nuances underpinning loot box engagement, yet remain consistent with narratives that policy action on loot boxes will have benefits for harm minimization., Competing Interests: This work was supported by funding from the charity GambleAware (a UK-based independent charity and strategic commissioner of gambling harm education, prevention, early intervention and treatment), and thus (via the funding model for GambleAware) the work was indirectly supported by voluntary contributions to GambleAware from the gambling industry., (© 2024 The Authors.)

Loot boxes are purchasable randomized rewards in video games that share structural and psychological similarities with gambling. Systematic review evidence has established reproducible associations between loot box purchasing and both problem gambling and problem video gaming, perhaps driven by a range of overlapping psychological processes (e.g. impulsivity, gambling-related cognitions, etc.) It has also been argued that loot box engagement may have negative influences on player financial and psychological wellbeing. We conducted a pre-registered survey of 1495 loot box purchasing gamers (LB cohort) and 1223 gamers who purchase other, non-randomized game content (nLB cohort). Our survey confirms 15 of our 23 pre-registered hypotheses against our primary outcome (risky loot box engagement), establishing associations with problem gambling, problem gaming, impulsivity, gambling cognitions, experiences of game-related 'flow' and specific 'distraction and compulsion' motivations for purchase. Results with hypotheses concerning potential harms established that risky loot box engagement was negatively correlated with wellbeing and positively correlated with distress. Overall, results indicate that any risks from loot boxes are liable to disproportionately affect various 'at risk' cohorts (e.g. those experiencing problem gambling or video gaming), thereby reiterating calls for policy action on loot boxes., Competing Interests: This work was supported by funding from the charity GambleAware (a UK-based independent charity and strategic commissioner of gambling harm education, prevention, early intervention and treatment), and thus (via the funding model for GambleAware) the work was indirectly supported by voluntary contributions to GambleAware from the gambling industry., (© 2023 The Authors.)

Introduction: Cavalier King Charles Spaniels (CKCS) are predisposed to developing myxomatous mitral valve disease (MMVD). Dogs with stage B2 MMVD benefit from medication., Objectives: To develop (1) breed-specific cut-offs for individual screening tests and (2) predictive models utilizing physical examination (PE), ECG, radiograph, and blood-based biomarker variables in combination for identification of echocardiographic stage B2 MMVD in preclinical CKCS., Animals: Adult, preclinical CKCS not receiving cardiac medications (N = 226)., Materials and Methods: Prospective, cross-sectional study. Enrolled CKCS underwent PE, ECG, radiography, Doppler blood pressure measurement, echocardiography, and biomarker testing. Dogs were grouped by MMVD stage using echocardiography only. The discriminatory ability of individual tests to identify stage B2 was assessed, and prediction models were developed using variables derived from four 'tests' (PE, ECG, radiography, and biomarkers)., Results: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and radiographic vertebral heart size (VHS) had the best discriminatory ability of individual diagnostic tests to differentiate stage A/B1 CKCS from stage B2, with an area under the curve (AUC) of 0.855 and 0.843, respectively. An NT-proBNP ≥1138 pmol/L or a VHS ≥11.5 had high specificity for predicting stage B2 (90.1% and 90.6%, respectively). Prediction models incorporating variables from multiple tests had better discriminatory ability than single tests. The four-test prediction model had an AUC of 0.971. Three and two-test models had AUCs ranging between 0.925-0.959 and 0.895-0.949, respectively., Conclusions: Both NT-proBNP and VHS have good utility for predicting echocardiographic stage B2 MMVD in CKCS as individual tests. Prediction models incorporating multiple test variables have superior discriminatory ability., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

A three-year-old, spayed female, Bichon Frise was diagnosed with an anomalous origin of the left coronary artery from the pulmonary artery, a rare congenital coronary artery defect which has only been reported in two other dogs. Echocardiography was initially performed, though the final diagnosis was made with angiography and computed tomography angiography. An extensive network of collateral coronary circulation allowed for communication between the dilated, tortuous right coronary artery, and the anomalous left coronary artery. Though collateral circulation likely prolonged the patient's life, it is suspected that coronary steal phenomenon and chronic myocardial ischemia ultimately led to fatal ventricular arrhythmias. The dog died suddenly at the age of six, three years after initial diagnosis., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The successful delivery of genetic material to gametes requires tightly regulated interactions between the parental chromosomes. Central to this regulation is a conserved chromosomal interface called the synaptonemal complex (SC), which brings the parental chromosomes in close proximity along their length. While many of its components are known, the interfaces that mediate the assembly of the SC remain a mystery. Here, we survey findings from different model systems while focusing on insight gained in the nematode C. elegans. We synthesize our current understanding of the structure, dynamics, and biophysical properties of the SC and propose mechanisms for SC assembly., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gordon, Rog. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cardiac troponin I (cTnI) is considered the gold standard biomarker for myocardial injury and shows a high degree of homology between humans and dogs. The ADVIA Centaur XP High-Sensitivity Troponin I (AC-cTnI-HS) assay has been validated for use in humans but not dogs. The study objectives were to analytically validate the AC-cTnI-HS assay in dogs, to assess correlation between the AC-cTnI-HS and a previous ADVIA Centaur TnI-Ultra (AC-cTnI-U) assay, to assess cTnI sample storage stability, and to clinically evaluate the AC-cTnI-HS assay in healthy dogs and dogs with cardiac disease. Canine serum samples were used for analytical validation. Intra- and inter-assay variability, dilutional parallelism, and spiking recovery were assessed. Samples from 196 client-owned dogs were evaluated (healthy dogs (n = 39) or dogs with congenital heart disease (n = 54), myxomatous mitral valve disease (n = 68), dilated cardiomyopathy (n = 15), or myocarditis (n = 20)). Inter- and intra-assay coefficient of variation (%CV) was between 2.8-41.4% and 3.8-30.2%, respectively, with pools with concentrations >20 pg/mL all having %CVs <10%. The observed to expected ratios for dilutional parallelism and spiking recovery experiments ranged between 92.3 and 266.7.0% and 84.3 and 108%, respectively. A strong correlation between the AC-cTnI-HS and AC-cTnI-U assays was observed (Spearman's ρ = 0.927), though a proportional bias existed, with AC-cTnI-HS assay concentrations being proportionally lower than AC-cTnI-U assay concentrations. Serum samples stored at -80°C had stable cTnI measurements for up to 2.7 years and after a single freeze-thaw cycle. Healthy dogs and dogs with congenital heart disease had significantly lower cTnI concentrations than dogs in the other three groups. The AC-cTnI-HS assay precisely, reproducibly, and accurately measures cTnI concentrations in dog serum with cTnI concentrations >20 pg/mL., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wesselowski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Geroscience studies of low-dose rapamycin in laboratory species have identified numerous benefits, including reversing age-related cardiac dysfunction. Cardiovascular benefits have been observed in dogs with 10 weeks of treatment, raising questions about possible benefits and adverse effects of long-term use of low-dose rapamycin. The objectives of this study were to assess the impact of 6 months of low-dose rapamycin on echocardiographic indices of cardiac function in healthy dogs and to document the occurrence of adverse events., Methods: Seventeen client-owned dogs aged 6-10 years, weighing 18-36 kg, and without significant systemic disease were included in a prospective, randomized, placebo-controlled, masked clinical trial. Low-dose rapamycin (0.025 mg/kg) or placebo was administered three times per week for 6 months. Baseline, 6-month, and 12-month evaluation included physical examination, cardiology examination, and clinicopathology. Three-month evaluation included physical examination and clinicopathology. Owners completed online questionnaires every 2 weeks., Results: There were no statistically significant differences in echocardiographic parameters between rapamycin and placebo groups at 6 or 12 months. No clinically significant adverse events occurred. In 26.8% of the bi-weekly surveys owners whose dogs received rapamycin reported perceived positive changes in behavior or health, compared to 8.1% in the placebo group ( p  = 0.04)., Discussion: While no clinically significant change in cardiac function was observed in dogs treated with low-dose rapamycin, the drug was well-tolerated with no significant adverse events., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Barnett, Wesselowski, Gordon, Saunders, Promislow, Schwartz, Chou, Evans, Kaeberlein and Creevy.)

In the absence of hearing during development, the brain adapts and repurposes what was destined to become auditory cortex. As cortical thickness is commonly used as a proxy to identify cortical regions that have undergone plastic changes, the purpose of this investigation was to compare cortical thickness patterns between hearing and deaf cats. In this study, normal hearing (n = 29) and deaf (n = 26) cats were scanned to examine cortical thickness in hearing controls, as well as differential changes in thickness as a consequence of deafness. In hearing cats, a gradient in cortical thickness was identified across auditory cortex in which it is thinner in more dorsal regions and thicker in more ventral regions. Compared with hearing controls, differential thickening and thinning was observed in specific regions of deaf auditory cortex. More dorsal regions were found to be bilaterally thicker in the deaf group, while more ventral regions in the left hemisphere were thinner. The location and nature of these changes creates a gradient along the dorsoventral axis, wherein dorsal auditory cortical fields are thicker, whereas more ventral fields are thinner in deaf animals compared with hearing controls., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: A point-of-care ultrasound (POCUS) protocol for evaluation of the cardiac and respiratory systems in horses does not exist., Objectives: (a) Describe the windows of a POCUS protocol for cardiorespiratory assessment of horses (CRASH); (b) Estimate the number of acoustic windows that can be acquired by a sonographer-in-training; (c) Estimate the time required to complete the protocol for specific groups of horses; (d) Describe the sonographic abnormalities detected in horses presented with cardiovascular, respiratory, or systemic disease., Animals: Twenty-seven healthy horses, 14 horses competing in athletic events, and 120 horses with clinical disease., Method: A pocket-sized ultrasound device was used to acquire 7 sonographic cardiorespiratory windows in various clinical scenarios. The duration of the examination was timed, and images were evaluated for diagnostic quality. Abnormalities in horses with clinical disease were determined by an expert sonographer., Results: The CRASH protocol could be performed in healthy and diseased horses in hospital, barn, and competition settings between 5.5 ± 0.9 (athletic horses) and 6.9 ± 1.9 min (horses with clinical disease). Thoracic windows were obtained most consistently, followed by right parasternal long-axis echocardiographic windows. Frequently detected abnormalities were pleural fluid, lung consolidation, B-lines, and moderate-to-severe left-sided heart disease., Conclusions: The CRASH protocol was feasible using a pocket-sized ultrasound device in various groups of horses, could be completed rapidly in a variety of settings, and frequently identified sonographic abnormalities when evaluated by an expert sonographer. The diagnostic accuracy, observer agreement, and utility of the CRASH protocol merit further evaluation., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

During meiosis, programmed double-strand DNA breaks are repaired to form exchanges between the parental chromosomes called crossovers. Chromosomes lacking a crossover fail to segregate accurately into the gametes, leading to aneuploidy. In addition to engaging the homolog, crossover formation requires the promotion of exchanges, rather than non-exchanges, as repair products. However, the mechanism underlying this meiosis-specific preference is not fully understood. Here, we study the regulation of meiotic sister chromatid exchanges in Caenorhabditis elegans by direct visualization. We find that a conserved chromosomal interface that promotes exchanges between the parental chromosomes, the synaptonemal complex, can also promote exchanges between the sister chromatids. In both cases, exchanges depend on the recruitment of the same set of pro-exchange factors to repair sites. Surprisingly, although the synaptonemal complex usually assembles between the two DNA molecules undergoing an exchange, its activity does not rely on a specific chromosome conformation. This suggests that the synaptonemal complex regulates exchanges-both crossovers and sister exchanges-by establishing a nuclear domain conducive to nearby recruitment of exchange-promoting factors., (© 2023 Almanzar et al.)

Background: Cardiac Rehabilitation is an essential following major adverse cardiovascular events however there is no current data correlating rehab performance to long term outcomes., Hypothesis: Patient exercise performance during cardiac rehabilitation reliably predicts future cardiovascular events., Methods: We conducted a single-center study of 486 consecutive patients who participated in a CR program between January 2018 and August 2021. We assessed patient performance using a novel index, the CR-score, which integrated duration, speed of work, and workload conducted on each training device (TD). We used a binary recursive partition model to determine the optimal thresholds for cumulative CR score. We used Cox regression analysis to assess the mortality rate among patients who developed MACE ("study group") and those who did not ("control group")., Results: Among 486 eligible patients, 1-year MACE occurred in 27 (5.5%) patients and was more common in patients with prior cerebrovascular accident or transient ischemic attack (14.8% vs. 3.5%, p < .001). Age, gender, comorbidities, heart failure, and medical treatment did not significantly affect the outcome. The median cumulative CR score of the study group was significantly lower than the control group (595 ± 185.6 vs. 3500 ± 1104.7, p < .0001). A cumulative CR-score of ≥1132 correlated with the outcome (98.5% sensitivity, 99.6% specificity, 95% CI: 0.985-0.997, area 0.994, p < .0001). Patients older than 55 with a cumulative CR score of <1132 were at particularly high risk (OR: 7.4, 95% CI: 2.84-18.42) for 1-year MACE (log-rank p = .03)., Conclusion: Our proposed CR-score accurately identifies patients at high risk for 1-year MACE following the rehabilitation program. Multicenter validation is required., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Introduction/objectives: Cavalier King Charles spaniels (CKCS) are ideal candidates for longitudinal study of myxomatous mitral valve (MV) disease and stage B1 clinical trials; however, the optimization of MV measurement acquisition and repeatability must be better defined to realize this potential. Additionally, breed-specific reference ranges for CKCS MV measurements are lacking. Study objectives were to assess measurement repeatability and define optimal methods for the longitudinal study of echocardiographic MV anatomy and to define preliminary, two-dimensional echocardiographic reference ranges for MV measurements in CKCS., Animals: Forty CKCS between 10 and 24 months old., Materials and Methods: Pre- and post-sedation two-dimensional echocardiographic images optimized for the MV were obtained. The length, width, and area of the anterior and posterior leaflets and the diameter of the MV annulus at end-diastole and end-systole were measured. Measurement repeatability was assessed using % coefficient of variation and repeatability coefficients., Results: Intraoperator repeatability was best for the operator with previous MV measurement experience, with comparable results for the experienced operator measuring the second operator's images, mimicking a core echocardiography laboratory setting. Except for MV annulus diameter at end-systole, sedation had no significant effect on any MV measurements, nor did it impact measurement repeatability. Preliminary, breed-specific reference ranges were defined for the population, with CKCS often noted to have a larger annular diameter at end-systole than end-diastole., Conclusions: Optimal methods for longitudinal study of the MV in CKCS have been proposed, as have two-dimensional preliminary echocardiographic reference ranges for CKCS MV measurements. The MV annulus in CKCS may differ from other breeds., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To determine breed-specific reference intervals for whole blood (WB) and plasma taurine concentrations in adult, overtly healthy Cavalier King Charles Spaniels (CKCSs) and determine whether taurine concentrations differ across preclinical myxomatous mitral valve disease (MMVD) stages or between CKCSs eating diets that meet World Small Animal Veterinary Association (WSAVA) nutritional guidelines versus other diets., Animals: 200 privately owned CKCSs., Procedures: Clinically healthy adult CKCSs were recruited prospectively. Diet and supplement history was collected. Dogs were staged by echocardiography using MMVD consensus guidelines. Taurine concentrations were measured in deproteinized lithium heparin WB and plasma samples with the postcolumn ninhydrin derivatization method on a dedicated amino acid analyzer., Results: There were 12 stage A (6%), 150 stage B1 (75%), and 38 stage B2 (19%) CKCSs. Seventy-eight dogs (39%) were reported by their owners to be eating diets meeting WSAVA nutritional guidelines; 116 (58%) were not. Taurine concentrations in plasma (P = .444) and WB (P = .073) were not significantly different across MMVD stages or between CKCSs eating diets meeting WSAVA nutritional guidelines versus other diets (P = .345 and P = .527, respectively). Reference intervals for WB taurine (152 to 373 µM) and plasma taurine (51 to 217 µM) concentrations in CKCSs were generated., Clinical Relevance: In CKCSs, taurine concentrations do not differ significantly based on preclinical MMVD stage, nor do they differ significantly based on consumption of a diet that does or does not meet WSAVA nutritional guidelines.

Background: N-terminal pro-brain natriuretic peptide (NT-proBNP) is a widely used point-of-care (POC) cardiac biomarker in human medicine. Canine NT-proBNP is used less in veterinary medicine, possibly due to the lack of a POC canine NT-proBNP assay resulting in temporal delay, increased degradation in transport, and high reported variability in the available assay. A new quantitative POC analyzer allows fast, onsite measurement of NT-proBNP, minimizing preanalytical error and reducing variability., Objective: We aimed to analytically validate an NT-proBNP assay (Vcheck) according to American Society of Veterinary Clinical Pathology (ASVCP) and Clinical Laboratory Improvement Amendments (CLIA) specifications., Methods: Archived and prospective plasma and serum samples were collected from male and female, client-owned dogs of various breeds with cardiac abnormalities (n = 81) and a healthy control population (n = 225). Precision, accuracy, analytical sensitivity, and specificity, and other statistical analyses were performed., Results: Imprecision was considered acceptable with a coefficient of variation ranging from 9% at 4000 pmol/L to 20% at 600 pmol/L. The lower limit of quantitation was 650 pmol/L based on repetitive measures evaluation. Comparison of the Vcheck assay with the Cardiopet NT-proBNP assay revealed an excellent correlation with minimal bias when preanalytical factors were controlled. Significant degradation of NT-proBNP occurred when current methods were used at refrigerated and room temperatures, which could change diagnostic and prognostic decision-making. Age-partitioned reference intervals have high reference values of 750 pmol/L and 1280 pmol/L for juvenile and adult dogs, respectively., Conclusions: The Vcheck NT-ProBNP assay provides analytically acceptable results. Onsite testing can minimize variability related to preanalytical error and provide clinically useful contemporaneous results. Samples should be centrifuged immediately and analyzed within 2 hours of collection., (© 2022 The Authors. Veterinary Clinical Pathology published by Wiley Periodicals LLC on behalf of American Society for Veterinary Clinical Pathology.)

Objectives: The objectives of the HOLISTIC Cohort Study are to establish a prospective cohort study covering a period of three years that characterizes the health of students within and across health professional education programs at the University of Illinois Chicago (UIC) during the coronavirus disease 2019 (COVID-19) pandemic, implement an interprofessional student research team, and generate a meaningful dataset that is used to inform initiatives that improve student health. This report describes the protocol of the HOLISTIC Cohort Study, including survey development, recruitment strategy, and data management and analysis., Methods: An interprofessional student research team has been organized with the goal of providing continuous assessment of study design and implementation across the seven health science colleges (applied health sciences, dentistry, medicine, nursing, pharmacy, public health, and social work) at the University of Illinois Chicago in Chicago, IL. To be eligible to participate in the HOLISTIC Cohort Study, students are required to be 1) age 18 years or older; 2) enrolled full- or part-time in one or more of UIC's seven health science colleges; and 3) enrolled in a program that prepares its graduates to enter a healthcare profession. The study protocol includes a series of three recruitment waves (Spring 2021 [April 14, 2021, to May 5, 2021; completed], Spring 2022, Spring 2023). In the first recruitment wave, eligible students were sent an invitation via electronic mail (e-mail) to complete an online survey. The online survey was based on the U.S. Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System 2019 survey and the 2014 World Health Organization Report of the Strategic Advisory Group of Experts Working Group Vaccine Hesitancy Scale. Electronic informed consent and study data are collected and managed using Research Electronic Data Capture (REDCap) tools. This study utilizes convenience sampling from all seven health science colleges at UIC with a target recruitment total of 2,000 participants., Discussion and Future Directions: A total of 555 students across all seven health science colleges (10.8% of 5,118 students who were invited; 27.6% of target sample size) enrolled in the cohort during the first recruitment wave. The pilot data establishes the feasibility of the study during the COVID-19 pandemic. Adaptations to overcome barriers to study implementation, including the use of remote, rather than in-person, study meetings, staff training, and participant recruitment are discussed. For the second and third waves of recruitment, the student research team will seek institutional review board (IRB) approval to implement additional enrollment strategies that are tailored to each health science college, such as online newsletters, virtual townhalls, flyers on bulletin boards near classrooms tailored to each health science college., Competing Interests: The authors have declared that no competing interests exist.

Background: Depression affects an individual's physical health and mental well-being and, in pregnant and postpartum women, has specific adverse short- and long-term effects on maternal, child, and family health. The aim of these two systematic reviews is to identify evidence on the benefits and harms of screening for depression compared to no screening in the general adult and pregnant and postpartum populations in primary care or non-mental health clinic settings. These reviews will inform recommendations by the Canadian Task Force on Preventive Health Care., Methods: We searched MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Library using a randomized controlled trial filter, where applicable, October 4, 2018, and updated to May 11, 2020. We also searched for gray literature (e.g., websites of organizations of health professionals and patients). Study selection for depression screening trials was performed first on title and abstract, followed by full-text screening. Data extraction, assessment of the risk of bias using the Cochrane risk of bias tool, and application of Grading of Recommendations Assessment, Development and Evaluation were performed by one reviewer and validated by a second reviewer., Results: A total of three trials were included. All three trials were included in the general adult review, while one of the three trials was included in the pregnant and postpartum review. We did not pool results due to substantial differences between studies and high risk of bias. In the general adult review, the first trial (n = 1001) evaluated whether screening for depression in adults with acute coronary syndrome compared to usual care improves health-related quality of life, depression symptoms, or harms of screening at 6, 12, and 18 months. There were little to no differences between the groups at 18 months for the outcomes. The second trial included adults (n = 1412) undergoing initial consultation for osteoarthritis, evaluated for depression and general health (mental and physical) after initial consultation and at 3, 6, and 12 months. The physical component score was statistically significantly lower (worse health) in the screened group at 6 months; however, this difference was not significant at 3 or at 12 months. There were no clinically important or statistically significant differences for other outcomes between groups at any time. The third trial (included in both reviews) reported on 462 postpartum women. At 6 months postpartum, fewer women in the screening group were identified as possibly depressed compared to the control group (RR 0.59, 95% confidence interval (CI) 0.39 to 0.89) and mean EPDS scores were also statistically significantly lower in the screened group (standardized mean difference 0.34 lower (95% CI 0.15 to 0.52 lower)). All other outcomes did not differ between groups at follow-up. There were serious concerns about the cut-offs used for the questionnaire used to screen, diagnostic confirmation, selective outcome reporting, and the reported magnitude of effects., Discussion: There are limitations of the evidence included in the reviews. There was moderate certainty in the evidence from one trial that screening for depression in the general adult population in primary care or non-mental health clinic settings likely results in little to no difference on reported outcomes; however, the evidence was uncertain from the other two included trials. The evidence is very uncertain about the effect of screening for depression in pregnant or postpartum women in primary care or non-mental health clinic settings. Well-conducted and better-reported trials are needed that meet the screening trial criteria used in this review., Systematic Review Registration: Both protocols have been registered in the International Prospective Registry of Systematic Reviews (PROSPERO) [adult: CRD42018099690 ; pregnancy and postpartum: CRD42018099689 ] and published ( https://systematicreviewsjournal.biomedcentral.com/track/pdf/10.1186/s13643-018-0930-3 )., (© 2022. The Author(s).)

Loot boxes are purchasable items in video games with a chance-based outcome. They have attracted substantial attention from academics and legislators over recent years, partly because of associations between loot box engagement and problem gambling. Some researchers have suggested that loot boxes may act as a gateway into subsequent gambling and/or problem gambling. However, such "gateway effects" have not been formally investigated. Using a survey of 1102 individuals who both purchase loot boxes and gamble, we found that 19.87% of the sample self-reported either "gateway effects" (loot boxes causally influencing subsequent gambling) or "reverse gateway effects" (gambling causally influencing subsequent loot box engagement). Both subsets of participants had higher scores for problem gambling, problem video gaming, gambling-related cognitions, risky loot boxes engagement, and impulsivity. These individuals also had a tendency for higher loot box and gambling spend; suggesting that potential gateway effects are related to measurable risks and harms. Moreover, the majority of participants reporting gateway effects were under 18 when they first purchased loot boxes. Content analysis of free text responses revealed several reasons for self-reported gateway effects, the most frequent of which were sensation-seeking, normalisation of gambling-like behaviours, and the addictive nature of both activities. Whilst the cross-sectional nature of our findings cannot conclusively establish directions of causality, thus highlighting the need for longitudinal research, we conclude that there is a case for legislation on loot boxes for harm minimisation purposes., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Loot boxes are purchasable randomised rewards in video games that share structural and psychological similarities with gambling. Systematic review evidence has established reproducible associations between loot box purchasing and both problem gambling and problem video gaming. We aimed to measure the association between loot box engagement and socioeconomic correlates., Design: The study was a cross-sectional online survey using the recruitment platform, Prolific., Setting: United Kingdom (UK)., Participants: A cohort of 16 196 UK adults (18 + years) self-reporting as video gamers., Measurements: Respondents were asked about their game-related purchasing behaviour (including loot boxes), recent monthly spend on loot boxes and gambling engagement (gambling in any form; gambling online; playing 'social casino' games). A range of demographic variables were simultaneously captured, including age, sex, ethnicity, earnings, employment and educational attainment., Findings: Overall, 17.16% of gamers in our cohort purchased loot boxes, with a mean self-reported monthly spend of £29.12. These loot box purchasers are more likely to gamble (45.97% gamble) than people who make other types of game-related purchases (on aggregate, 28.13% of non-loot box purchasers gamble), and even greater still than those who do not make any game related purchases (24.38% gamble P < 0.001). Loot box engagement (as binary yes/no or as monthly spend normalised to earnings) was significantly associated with younger age (P < 0.001 and P < 0.001; respectively, for binary yes/no and monthly spend, adjusted for false discovery rate correction), male sex (P < 0.001 and P = 0.025), non-university educational attainment (P < 0.001 and P < 0.001) and unemployment (P = 0.003 and P = < 0.001). Lower earners spent a higher proportion of monthly earnings on loot boxes (P < 0.001)., Conclusions: The demographic associations of video game loot box engagement (younger age, male sex, non-university educational attainment and unemployment) mirror those of other addictive and problematic behaviours, including disordered gambling, drug and alcohol misuse., (© 2022 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Introduction/objectives: Intracardiac echocardiography (ICE) is a method of obtaining echocardiographic images with a steerable ultrasound catheter placed within the heart via a venous or arterial approach. The objectives of this study were to assess the feasibility of a 5-10 MHz, 8 French, 90 cm ICE catheter to evaluate cardiac structures and function in standing, sedated horses, and describe standard views in this species., Animals: Ten apparently healthy horses weighing 458.1-618.2 kg from a university teaching herd., Materials and Methods: Each horse had a physical examination, transthoracic echocardiography, and ICE performed through a 10 French introducer percutaneously placed in the right jugular vein in the proximal third of the neck with continuous ECG monitoring using telemetry., Results: Three intracardiac echocardiography positions (cranial right atrium, mid right atrium, and right ventricle) with seven views were described with the associated 2D, pulse wave Doppler, continuous wave Doppler, color Doppler, and M-mode image acquisition standardized by referencing the intracardiac positions and common landmarks. The positions were confirmed with simultaneous transthoracic echocardiography. The procedure was well tolerated with only mild, occasional ventricular, and supraventricular arrhythmias that resolved with intracardiac echocardiography catheter repositioning., Conclusions: Intracardiac echocardiography is feasible, safe, and allows for the acquisition of diagnostic images in conscious, sedated horses., Competing Interests: Conflict of Interest Statement The authors do not have any conflicts of interest to disclose., (Published by Elsevier B.V.)

Genome-wide association studies (GWAS) have identified a number of risk loci for cutaneous melanoma. Cutaneous melanoma shares overlapping genetic risk (genetic correlation) with a number of other traits, including its risk factors such as sunburn propensity. This genetic correlation can be exploited to identify additional cutaneous melanoma risk loci by multitrait analysis of GWAS (MTAG). We used bivariate linkage disequilibrium-score regression score regression to identify traits that are genetically correlated with clinically confirmed cutaneous melanoma and then used publicly available GWAS for these traits in a multitrait analysis of GWAS. Multitrait analysis of GWAS allows GWAS to be combined while accounting for sample overlap and incomplete genetic correlation. We identified a total of 74 genome-wide independent loci, 19 of them were not previously reported in the input cutaneous melanoma GWAS meta-analysis. Of these loci, 55 were replicated (P < 0.05/74, Bonferroni-corrected P-value in two independent cutaneous melanoma replication cohorts from Melanoma Institute Australia and 23andMe, Inc. Among the, to our knowledge, previously unreported cutaneous melanoma loci are ones that have also been associated with autoimmune traits including rs715199 near LPP and rs10858023 near AP4B1. Our analysis indicates genetic correlation between traits can be leveraged to identify new risk genes for cutaneous melanoma., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction/objectives: Minimal information exists regarding epicardial pacemaker (EP) implantation in pet ferrets (Mustela putorius furo). The objectives were to describe the indications, surgical technique, and outcome of EP implantation in ferrets for the treatment of advanced atrioventricular block (AVB)., Animals, Materials, and Methods: Eight client-owned ferrets presenting to five veterinary referral centers. Signalment, physical exam findings, diagnostic tests, anesthesia protocols, surgical implantation techniques, postoperative treatment plans, and EP interrogations were reviewed. Intra- and postoperative, minor and major, and EP-related complications were established. Descriptive statistics were performed to report complication rates. Survival analyses were performed., Results: All ferrets had advanced AVB: 3/8 had high-grade second-degree and 5/8 had third-degree. The primary clinical signs were collapse and weakness. Seven EP were implanted via a transdiaphragmatic approach and one via a left intercostal thoracotomy. Intraoperative complications occurred in 2/8 ferrets, both major. One ferret with severe comorbidities died during general anesthesia. Postoperative pacemaker-related complications were minor: inappropriate sinus beat sensing in 2/8 and occasional muscle fasciculations in 1/8. Two ferrets were alive at the time of manuscript submission, at 10 and 21 months postoperatively. The overall median survival time was 24 months., Conclusions: Implantation of EP was performed successfully in most ferrets for treatment of advanced AVB and was well tolerated. Ferrets with advanced AVB may experience resolution of clinical signs associated with their cardiac disease following EP implantation. Additional studies are warranted to investigate the effects of epicardial pacing on survival times in this species., Competing Interests: Conflicts of Interest Statement The authors have no conflicts of interest to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Degenerative valve disease (DVD) is the leading cause of heart disease and heart failure in the dog. The first consensus statement published in 2009 by the American College of Veterinary Internal Medicine was updated in 2019 and provides guidelines for the diagnosis and treatment of DVD. These updated guidelines recommend treatment with pimobendan in stage B2 DVD characterized by sufficient left heart enlargement. Asymptomatic dogs with DVD that do not meet or exceed the definition of stage B2 are considered stage B1. No treatment is recommended in stage B1 DVD. This article discusses the relevant scientific background and practical application of the updated DVD guidelines related to stage B. In addition, management of common sequelae of DVD that can result in clinical signs unrelated to congestive heart failure will be reviewed. The impact of new evidence on current recommendations and a glimpse into novel diagnostic approaches and possible future therapies will also be addressed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Large breed (LB) dogs develop dilated cardiomyopathy (DCM) and myxomatous mitral valve disease (MMVD). Echocardiography is required for a definitive diagnosis but is not always available. Our objective was to assess the clinical utility of thoracic radiographs alone and in combination with physical examination and electrocardiography findings for the prediction of clinically important DCM or MMVD in LB dogs., Animals: Four hundred fifty-five client-owned dogs ≥20 kg with concurrent thoracic radiographs and echocardiogram., Materials and Methods: Medical records were reviewed and stored thoracic radiographs and echocardiographic images were measured to classify dogs as normal heart size (NHS), preclinical DCM, clinical DCM, preclinical MMVD (with cardiomegaly), clinical MMVD, or equivocal. Dogs with preclinical MMVD, without cardiomegaly, were classified as NHS. Vertebral heart size (VHS) and vertebral left atrial size (VLAS) were measured. Receiver operating characteristic curves and prediction models were derived., Results: Prevalence of MMVD (39.3%) was higher than the prevalence of DCM (24.8%), though most MMVD dogs (67.0%) lacked cardiomegaly and were classified as NHS for analysis. The area under the curve for VHS to discriminate between NHS and clinical DCM/MMVD or preclinical DCM/MMVD was 0.861 and 0.712, respectively, while for VLAS, it was 0.891 and 0.722, respectively. Predictive models incorporating physical examination and electrocardiography findings in addition to VHS/VLAS increased area under the curve to 0.978 (NHS vs. clinical DCM/MMVD) and 0.829 (NHS vs. preclinical DCM/MMVD)., Conclusions: Thoracic radiographs were useful for predicting clinically important DCM or MMVD in LB dogs, with improved discriminatory ability when physical examination abnormalities and arrhythmias were accounted for., Competing Interests: Conflict of Interest Statement The authors do not have any conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Screening to assess likelihood of preclinical dilated cardiomyopathy (PC-DCM) prior to advanced diagnostic tests in Doberman Pinschers (DP) is desirable., Objective: To investigate the combined value of physical examination (PE), N-terminal pro B-type natriuretic peptide (NTproBNP) and cardiac troponin I (cTnI) for identifying PC-DCM in DP., Animals, Materials and Methods: All dogs underwent: PE, echocardiogram, 3-min ECG and cardiac biomarker measurement. Asymptomatic DP (414) were classified based on 3-min ECG and echocardiogram as: No-DCM/MMVD or myxomatous mitral valve disease (MMVD), PC-DCM based on echocardiogram (PC-DCM-Echo), PC-DCM based on arrhythmias with a normal echocardiogram (PC-DCM-ECG), equivocal DCM (EQ-DCM), and MMVD. Receiver operator characteristic curves and prediction models were derived., Results: Heart murmurs and arrhythmias were rare and gallop sounds were absent in No-DCM/MMVD DP. Dogs ≥ four years old and males had higher probabilities of PC-DCM-Echo. Prediction models incorporating PE variables with NTproBNP had an area under the curve (AUC) of 0.940 for distinguishing between PC-DCM-Echo and all other groups, which was similar to the AUC for NTproBNP (0.939) or cTnI (0.932) alone. Discrimination between No-DCM/MMVD and all other groups was similar for NTproBNP (0.781) and cTnI (0.742) as individual tests, however, models combining PE variables and NTproBNP increased the AUC to 0.812. An NTproBNP cut-off of ≥548 pmol/L, was 100% sensitive and 77.3% specific for detecting PC-DCM-Echo., Conclusions: Both NTproBNP and cTnI had good utility as sole tests to discriminate PC-DCM-Echo DP from all others. Models differentiating No-DCM/MMVD DP from all other DP were improved by using PE and NTproBNP together., Competing Interests: Conflicts of Interest Statement Drs. Gordon, Häggström, Estrada and O'Grady have received funding from Boehringer Ingelheim Animal Health GmbH within the last five years for some or all of the following activities: research, travel, speaking fees, consultancy fees, and preparation of educational materials. Drs. Gordon, Wesselowski, and Estrada have received funding from IDEXX Laboratories within the last five years for some or all of the following activities: research, travel, speaking fees, consultancy fees, and preparation of educational materials., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Qualitative studies have identified a diverse array of motivations for purchasing items within video games through chance-based mechanisms (i.e., "loot boxes"). Given that some individuals-particularly those at risk of disordered gaming and/or gambling-are prone to over-involvement with loot box purchasing, it is important to have a reliable, valid means of measuring the role of different motivations in driving purchasing behaviour. Building on prior qualitative research, this paper reports the development and validation of the "RAFFLE" scale, to measure the Reasons and Facilitators for Loot box Engagement. A 23-item, seven-factor scale was developed through cognitive interviews ( n = 25) followed by two surveys of UK-based gamers who purchase loot boxes; analysed via exploratory ( n = 503) and confirmatory ( n = 1495) factor analysis, respectively. Subscales encompassed "enhancement'; "progression'; "social pressure'; "distraction/compulsion'; "altruism'; "fear of missing out'; and "resale". The scale showed good criterion and construct validity (correlating well with measures of loot box engagement; the risky loot box index ( r = 0.63) and monthly self-reported spend ( r = 0.38)), and good internal validity (Cronbach's alpha = 0.84). Parallels with, and divergence from, motivations for related activities of gaming and gambling, and alignment with broader theoretical models of motivation, are discussed.

Alignment of the parental chromosomes during meiotic prophase is key to the formation of genetic exchanges, or crossovers, and consequently to the successful production of gametes. In almost all studied organisms, alignment involves synapsis: the assembly of a conserved inter-chromosomal interface called the synaptonemal complex (SC). While the SC usually synapses homologous sequences, it can assemble between heterologous sequences. However, little is known about the regulation of heterologous synapsis. Here, we study the dynamics of heterologous synapsis in the nematode C. elegans. We characterize two experimental scenarios: SC assembly onto a folded-back chromosome that cannot pair with its homologous partner; and synapsis of pseudo-homologs, a fusion chromosome partnering with an unfused chromosome half its size. We observed elevated levels of heterologous synapsis when the number of meiotic double-strand breaks or crossovers were reduced, indicating that the promiscuity of synapsis is regulated by break formation or repair. In addition, our data suggests the existence of both chromosome-specific and nucleus-wide regulation on heterologous synapsis., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The protozoal parasite Trypanosoma cruzi causes myocarditis in dogs., Objectives: To describe the cardiac diagnostic test results and outcomes of dogs naturally infected with T. cruzi., Animals: Forty-four client-owned dogs., Methods: Medical records were retrospectively reviewed to identify dogs with an indirect fluorescent antibody test result for T. cruzi ≥1 : 80. Data collected included signalment, cardiac diagnostic test results (ECG, echocardiography, cardiac troponin I) and outcome. Outcomes were categorized as alive, dead (cardiac or noncardiac) or lost to follow up., Results: ECG abnormalities were present in 41 dogs with ventricular arrhythmias (n = 28) and atrioventricular block (AVB) (n = 15) most commonly identified. Echocardiographic chamber enlargement was present in 28 dogs and most often included the right ventricle (RV) (n = 15) and left atrium (n = 12). Troponin was ≥2 times the reference range in 20/36 (56%) dogs. In univariate analysis using nonparametric Kaplan-Meier, ventricular arrhythmias with a modified Lown score ≥2 (P = .02), presence of AVB (P = .04), and RV enlargement (P = .006) were associated with decreased survival times. Right ventricular enlargement (HR 3.6; 95% confidence interval [CI] 1.4-9.3; P = .007) and higher body weight at presentation (HR 1.0; 95% CI 1.0-1.1; P = .04) were associated with decreased time to death in the final explanatory multivariable model., Conclusions and Clinical Importance: Cardiac abnormalities were common and variable, and RV enlargement was associated with shorter survival time. A diagnostic evaluation that includes screening for arrhythmias, echocardiography, and cTnI can provide useful information related to the characterization of heart disease in dogs seropositive for T. cruzi., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Introduction: Loot boxes are purchasable randomised reward mechanisms in video games. Due to structural and psychological similarities with gambling, there are fears that loot box purchasing may be associated with problematic gambling. Whilst monthly expenditure is typically modest (i.e. < $20), the distribution is highly skewed, with a small number of high-level spenders, sometimes referred to as "whales". It is not known what proportion of industry profits are derived from such players, and whether they are typically wealthy individuals and/or problem gamblers., Methods: We used structured literature searches to identify surveys of gamers with open-access loot box data. The resulting datasets were aggregated, and correlations between loot box expenditure, problem gambling and earnings investigated using Spearman's rho correlations., Results: The combined open-access data comprised 7,767 loot box purchasers (5,933 with self-report earnings). Secondary analysis of this self-report data confirmed that disproportionate revenue appears to be generated from high-level spenders: the top 5% of spenders (> $100/month) represent half of loot box revenue. Previously reported correlations between problem gambling and loot box expenditure were confirmed, with an aggregate correlation of ρ = 0.34, p < .001. In contrast, there was no significant correlation between loot box spend and earnings ρ = 0.02, p = .10., Conclusion: Our secondary analysis suggests that games developers (unwittingly or not) are disproportionately profiting from moderate and high-risk gamblers, rather than high earning customers. Such patterns of spending mirror those observed with gambling revenues, and have implications for harm minimisation and ongoing policy debates around loot boxes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Excessive engagement with (increasingly prevalent) loot boxes within games has consistently been linked with disordered gambling and/or gaming. The importance of recognising and managing potential risks associated with loot box involvement means understanding contributing factors is a pressing research priority. Given that motivations for gaming and gambling have been informative in understanding risky engagement with those behaviours, this qualitative study investigated motivations for buying loot boxes, through in-depth interviews with 28 gamers from across the UK. A reflexive thematic analysis categorised reasons for buying into seven "themes"; opening experience; value of box contents; game-related elements; social influences; emotive/impulsive influences; fear of missing out; triggers/facilitators. These themes are described in detail and discussed in relation to the existing literature and motivation theories. This study contributes to understanding ways in which digital items within loot boxes can be highly valued by purchasers, informing the debate around parallels with gambling. Findings that certain motivations were disproportionately endorsed by participants with symptoms of problematic gambling has potential implications for policy and warrants further study.