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Background: Total hip replacement (THR) in the gold standard surgical treatment for the canine hip. While it has been shown that greater trochanter morphology affects post-operative cementless stem position in humans, trochanter morphology and the effect on cementless stem position has not been extensively evaluated in dogs. The objective of this study was to classify greater trochanter morphology and identify potential associations between trochanter morphology and patient demographics, femoral canal geometry, surgical time, technique modifications, and post-operative stem position in client-owned dogs undergoing cementless THR., Results: In this retrospective study, medical records and radiographs of 135 dogs undergoing 150 cementless total hip replacements from 2013 to 2020 were included. Trochanters were classified in the frontal plane using an ordinal grading system adapted from human THR. A Grade I trochanter denoted a trochanter positioned lateral to the periosteal surface of the lateral femoral cortex, whereas a Grade IV trochanter denoted a trochanter positioned medial to the anatomic axis of the femur. Associations between trochanter grade and other variables were examined using ANOVA, Kruskall-Wallis, or chi-squared tests. Significance was assumed at P ≤ .05. Trochanters were classified as follows: Grade I (44/150, 29.3%), Grade II (56/150, 37.4%), Grade III (44/150, 29.3%), Grade IV (6/150, 4.0%). Grade IV trochanters had lower anatomic lateral distal femoral angle (aLDFA; 91.0 ± 6.2°), angle of inclination (117.7 ± 10.5°), and canal flare index (1.53 ± 0.27). When compared to all groups, Grade IV trochanters were associated with longer surgical times (Grade IV: 227.0 ± 34.2 min; all grades: 183.2 ± 32.9 min) and technique modifications (Grade IV: 83.3%; all grades: 18%). Grade I trochanters had stems placed in valgus (- 1.8 ± 2.33°), whereas Grade II (0.52 ± 2.36°), III (0.77 ± 2.58°), and IV (0.67 ± 2.73°) trochanters exhibited varus stems. Depth of stem insertion was greater (11.2 ± 4.2 mm) for Grade IV trochanters., Conclusions: Trochanter grade was associated with post-operative stem alignment and translation in the frontal plane. Grade IV trochanters were associated with altered femoral geometry, increased surgical time, technique modifications, and stem insertion depth. Pre-operative greater trochanter classification may prove useful in identifying cases requiring prolonged surgical times or technique modifications., (© 2022. The Author(s).)

Many biological science PhD graduates are increasingly pursuing careers outside of academia. Subsequently, PhD training programs are increasing their efforts to broaden their awareness of diverse career opportunities, with a firm knowledge of the skills necessary for success. At Yale University, for two semesters we have offered a new course for graduate students in the biological sciences titled "Skills Development for Diverse Scientific Careers" (BBS 550b). This course addressed career-related topics not covered in any curriculum at Yale such as how to run clinical trials, the business side of biotech, how to convert CVs into resumes, and resilience for early career scientists. We sought to better equip students to think broadly about their career options by exposing them to non-academic biomedical career avenues. Furthermore, the course fulfilled a gap in current curricular offerings to prepare students for multiple science career trajectories. Results on a pre-post course survey demonstrated increases in students' interest for, knowledge of, and confidence in securing a position in multiple nontraditional career sectors. Intentional course design can provide an adequate foundation to broaden awareness of myriad career options available to bioscientists. Broadening student knowledge and interest levels will contribute substantially to developing a robust scientific workforce., Competing Interests: The authors declare no conflicts of interest., (©2021 The Authors FASEB BioAdvances published by The Federation of American Societies for Experimental Biology.)

Objective: Hydrocephalus is a disorder of cerebrospinal fluid dynamics, traditionally treated by placement of a ventricular shunt. Shunts are effective but imperfect as they fail in an unpredictable pattern, and the patient's well-being is dependent on adequate shunt function. The omnipresent threat of shunt failure along with the potential need for invasive investigations can be stressful for patients and caregivers. Our objective was to measure post-traumatic stress symptoms (PTSS) in children with hydrocephalus and their caregivers., Methods: A cross-sectional analysis of children with hydrocephalus and their caregivers was conducted. Caregivers completed a measure of their own PTSS (the Post-Traumatic Stress Disorders Checklist for the Diagnostic and Statistical Manual of Mental Disorders-V) and resilience (the Connor Davidson Resilience Scale). Pediatric patients rated their own PTSS and resilience using the Acute Stress Checklist for Kids and Connor Davidson Resilience Scale., Results: Ninety-one caregivers completed the Post-Traumatic Stress Disorders Checklist for the Diagnostic and Statistical Manual of Mental Disorders-V. Mean score was 17.0 (standard deviation 15.7; median 13.0). Fourteen percent scored above 33, the threshold suggestive of a preliminary diagnosis of post-traumatic stress disorder. There was a statistically significant association between caregiver post-traumatic stress and marital status, child's race, and caregiver education. More than half (52%) of caregivers reported their child's hydrocephalus as the most significant source of their PTSS. Children did not have markedly elevated levels of PTSS. Forty-one percent of caregivers and 60% of children scored in the lowest resilience quartile compared with the general population., Conclusions: Results from this study suggest that post-traumatic stress affects caregivers with hydrocephalus, yet levels of resilience for caregivers and pediatric patients are low., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: In Australia, the National Safety and Quality Health Service Standards (2012) stipulates that partnering with health consumers to improve health-care experiences is one of the criteria health-care organizations are assessed and accredited against. This standard has given rise to a role: health engagement professionals (HEPs). While there are no standard requirements for recruitment into this role, this study contributes to much needed research into understanding their responsibilities and capabilities, and their contributions to engagement outcomes., Methods: Using a qualitative, interpretive approach, 16 HEPs and 15 health consumer representatives (who have experiences of interacting with HEPs) participated in an in-depth phone interview in December 2019. We explored (a) the purposes of the role, (b) the responsibilities and work activities and (c) the capabilities required to carry out the responsibilities., Results: Health engagement professionals are specialists in designing engagement mechanisms for health-care organizations to co-design health services with health consumers. They facilitate partnerships between health-care organizations and health consumers. They play significant roles in listening to, facilitating understanding amongst different stakeholder groups (eg hospital management, health-care workers and health consumers) and navigating the bureaucratic structures to influence outcomes. Four major responsibilities (advocacy, education, facilitation and administration) and four categories of capabilities (relational, communication, professional and personal) were identified., Conclusion: A list of job responsibilities and desired capabilities of HEPs is provided to help health-care organizations better understand the requirements for the role. This would help them decide how applicants to these roles would meet the requirements (eg experience of navigating bureaucratic systems)., (© 2020 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Objective: To evaluate the effect of sedation or general anesthesia (GA) on elbow goniometry and thoracic limb circumference (TLC) measurements in dogs with elbow osteoarthritis (OA)., Study Design: Prospective study., Animals: Twenty-four client-owned dogs with radiographically confirmed elbow OA., Methods: Elbow goniometry and TLC measurements were made before and after either sedation or GA by using a hand-held goniometer and spring tension measuring tape, respectively. Observers were not allowed to review their pre-sedation or pre-GA measurements at the time of obtaining measurements on dogs under sedation or GA. Mixed analysis of variance models were used to compare elbow goniometry and TLC measurements before and after sedation or GA., Results: Eleven and thirteen dogs were included in the sedation and GA groups, respectively. Mean elbow flexion decreased by 5° and 3° and mean elbow extension increased by 6° and 2° under sedation and GA, respectively. Total range of motion increased by 11° under sedation and by 5° under GA. Each of these changes was statistically significant (P < .05) except elbow extension under GA (P = .129). Sedation and GA did not influence TLC measurements (P > .05)., Conclusion: Sedation or GA led to slight and similar increase in elbow flexion and extension but did not influence TLC measurements in dogs with elbow OA., Clinical Significance: Sedation or GA can cause slight alterations to goniometric measurements in canine elbows with OA. The protocols used in this study for sedation and GA seem interchangeably acceptable for goniometry and TLC measurements in dogs with elbow OA., (© 2020 American College of Veterinary Surgeons.)

Dysregulation of ribosome production can lead to a number of developmental disorders called ribosomopathies. Despite the ubiquitous requirement for these cellular machines used in protein synthesis, ribosomopathies manifest in a tissue-specific manner, with many affecting the development of the face. Here we reveal yet another connection between craniofacial development and making ribosomes through the protein Paired Box 9 (PAX9). PAX9 functions as an RNA Polymerase II transcription factor to regulate the expression of proteins required for craniofacial and tooth development in humans. We now expand this function of PAX9 by demonstrating that PAX9 acts outside of the cell nucleolus to regulate the levels of proteins critical for building the small subunit of the ribosome. This function of PAX9 is conserved to the organism Xenopus tropicalis, an established model for human ribosomopathies. Depletion of pax9 leads to craniofacial defects due to abnormalities in neural crest development, a result consistent with that found for depletion of other ribosome biogenesis factors. This work highlights an unexpected layer of how the making of ribosomes is regulated in human cells and during embryonic development., Competing Interests: The authors have declared that no competing interests exist.

Objective: Childhood hydrocephalus is a common chronic medical condition. However, little is known about the burden of headache and psychological comorbidities in children living with hydrocephalus. The purpose of this study was to determine the prevalence and severity of these conditions among the pediatric hydrocephalus population., Methods: During routine neurosurgery clinic visits from July 2017 to February 2018, the authors administered four surveys to children ages 7 years and older: Pediatric Migraine Disability Assessment (PedMIDAS), Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, PROMIS Depression, and PROMIS Fatigue. The PedMIDAS is an assessment of headache disability in pediatric and adolescent patients. The PROMIS measures are pediatric self-reported instruments to assess social and emotional health. PROMIS measures utilize T-scores (mean 50, SD 10) to compare anxiety, depression, and fatigue in specific populations to those in the US general population. Clinical and demographic data were collected from the medical record (hydrocephalus etiology, shunt infection, race, etc.) and tested for associations with survey measure scores., Results: Forty children completed the PedMIDAS. Ten percent of them were in the severe headache range, 5% were in the moderate range, and 5% were in the mild range. There was a statistically significant association between undergoing a cluster of shunt operations and headache burden (p = 0.003).Forty children completed all three PROMIS measures. The mean anxiety score was 45.8 (SD 11.7), and 2.5% of children scored in the severe anxiety range, 17.5% in the moderate range, and 20% in the mild range. The mean depression score was 42.7 (SD 10.0), with 2.5% of children scoring in the severe depression range, 5% in the moderate range, and 12.5% in the mild range. The mean fatigue score was 45.1 (SD 16.4), with 15% percent of children scoring in the severe fatigue range, 10% in the moderate range, and 7.5% in the mild range. There were no statistically significant associations between child anxiety, depression, or fatigue and clinical or demographic variables., Conclusions: Children with hydrocephalus have an average burden of headache, anxiety, depression, and fatigue as compared to the general population overall. Having a cluster of shunt operations correlates with a higher headache burden, but no clinical or demographic variable is associated with anxiety, depression, or fatigue.

Objective: Hydrocephalus is a chronic medical condition that has a significant impact on children and their caregivers. The objective of this study was to measure the quality of life (QOL) of children with hydrocephalus, as assessed by both caregivers and patients., Methods: Pediatric patients with hydrocephalus and their caregivers were enrolled during routine neurosurgery clinic visits. The Hydrocephalus Outcomes Questionnaire (HOQ), a report of hydrocephalus-related QOL, was administered to both children with hydrocephalus (self-report) and their caregivers (proxy report about the child). Patients with hydrocephalus also completed measures of anxiety, depression, fatigue, traumatic stress, and headache. Caregivers completed a proxy report of child traumatic stress and a measure of caregiver burden. Demographic information was collected from administration of the Psychosocial Assessment Tool (version 2.0) and from the medical record. Child and caregiver HOQ scores were analyzed and correlated with clinical, demographic, and psychological variables., Results: The mean overall HOQ score (parent assessment of child QOL) was 0.68. HOQ Physical Health, Social-Emotional Health, and Cognitive Health subscore averages were 0.69, 0.73, and 0.54, respectively. The mean overall child self-assessment (cHOQ) score was 0.77, with cHOQ Physical Health, Social-Emotional Health, and Cognitive Health subscore means of 0.84, 0.79, and 0.66, respectively. Thirty-nine dyads were analyzed, in which both a child with hydrocephalus and his or her caregiver completed the cHOQ and HOQ. There was a positive correlation between parent and child scores (p < 0.004 for all subscores). Child scores were consistently higher than parent scores. Variables that showed association with caregiver-assessed QOL in at least one domain included child age, etiology of hydrocephalus, and history of endoscopic third ventriculostomy. There was a significant negative relationship (rho -0.48 to -0.60) between child-reported cHOQ score and child-reported measures of posttraumatic stress, anxiety, depression, and fatigue. There was a similar significant relationship between caregiver report of child's QOL (HOQ) and caregiver assessment of the child's posttraumatic stress symptoms as well as their assessment of burden of care (rho = -0.59 and rho = -0.51, respectively). No relationship between parent-reported HOQ and child-reported psychosocial factors was significant. No clinical or demographic variables were associated with child self-assessed cHOQ., Conclusions: Pediatric patients with hydrocephalus consistently rate their own QOL higher than their caregivers do. Psychological factors such as anxiety and posttraumatic stress may be associated with lower QOL. These findings warrant further exploration.

Objective: To determine the influence of orthopedic examination on numerical rating score (NRS) and visual analog score (VAS) when scoring lameness in dogs with elbow osteoarthritis (OA) and to evaluate interobserver and intraobserver agreement in NRS and VAS on the basis of video-graphic gait analysis., Design: Prospective blinded study., Animals: Eighteen client-owned dogs with radiographically confirmed elbow OA., Methods: Videos were obtained for all dogs at a walk and at a trot both prior to and immediately after orthopedic examination. All videos were randomly sequenced. Six observers, unaware of the timing of the video, independently assigned both NRS and VAS twice, with at least a 2-week interval. Scores were evaluated with mixed analysis of variance, and the agreement among observers was accessed by intraclass correlation coefficient (ICC)., Results: No difference was detected between NRS and VAS at walk or at trot before and after orthopedic examination. Numeric rating score and VAS at walk were lower than those at trot before an orthopedic examination by scores of 0.17 (P = .0018) and 3.54 (P = .0019), respectively. The ICC for both scores for all observers was >0.9., Conclusion: An orthopedic examination did not exacerbate the NRS and the VAS for dogs with elbow OA. Interobserver and intraobserver agreement was high for both lameness scores., Clinical Significance: Lameness may be scored after gait evaluation in dogs with elbow OA irrespective of the timing of a comprehensive orthopedic examination., (© 2020 The American College of Veterinary Surgeons.)

Ribosomopathies are a diverse subset of diseases caused by reduced expression of, or mutations in, factors necessary for making ribosomes, the protein translation machinery in the cell. Despite the ubiquitous need for ribosomes in all cell types, ribosomopathies manifest with tissue-specific defects and sometimes increased cancer susceptibility, but few treatments target the underlying cause. By highlighting new research in the field, we review current hypotheses for the basis of this tissue specificity. Based on new work, we broaden our understanding of the role of ribosome biogenesis in diverse tissue types throughout embryonic development. We also pose the question of whether previously described human conditions such as aging can be at least partially attributed to defects in making ribosomes., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Sarcopenia is characterised by loss of skeletal muscle mass and strength with adverse outcomes: physical disability, poor quality of life and death. Low muscle mass and strength are risk factors for falls, although there are few data available on the prevalence of sarcopenia in fallers. This study aimed to determine prevalence of sarcopenia in older people referred to a falls clinic., Methods: Consecutive patients referred to a secondary care falls unit were recruited. Sarcopenia was diagnosed using the European Working Group on Sarcopenia definition (low muscle mass and function) and cut-off points. Bio-impedance measured appendicular skeletal muscle mass. Gait speed and grip strength were functional measures., Results: Fifty-eight patients were recruited. Mean (SD) grip strength for women and men respectively were 17.9 (4.9) and 29.9(8.7) kg, mean (SD) gait speeds were 0.61(0.18) and 0.72 (0.4) m/s, mean (SD) appendicular skeletal muscle index in women and men were 6.98(1.0) and 7.85 (1.0) kg/m 2 (p=0.018). Prevalence of sarcopenia was 9.8% (95% CI=1.6%-18%)., Conclusions: Sarcopenia, as measured by bio-impedance is not uncommon in older people accessing a secondary care falls clinic. Bio-impedance was simple to perform, although further validation against gold standard methods is needed. As nutritional and exercise interventions for sarcopenia are available, simple methods for diagnosing sarcopenia in fallers should be considered., (Copyright: © 2018 Hylonome Publications.)

Ribosome biogenesis is a highly regulated, essential cellular process. Although studies in yeast have established some of the biological principles of ribosome biogenesis, many of the intricacies of its regulation in higher eukaryotes remain unknown. To understand how ribosome biogenesis is globally integrated in human cells, we conducted a genome-wide siRNA screen for regulators of nucleolar number. We found 139 proteins whose depletion changed the number of nucleoli per nucleus from 2-3 to only 1 in human MCF10A cells. Follow-up analyses on 20 hits found many (90%) to be essential for the nucleolar functions of rDNA transcription (7), pre-ribosomal RNA (pre-rRNA) processing (16), and/or global protein synthesis (14). This genome-wide analysis exploits the relationship between nucleolar number and function to discover diverse cellular pathways that regulate the making of ribosomes and paves the way for further exploration of the links between ribosome biogenesis and human disease., (Copyright © 2018 Susan J. Baserga, Yale University School of Medicine, New Haven, CT USA. Published by Elsevier Inc. All rights reserved.)

Background: Early development appears normal in Rett syndrome (OMIM #312750) and may be more apparent than real. A major purpose of the Rett Syndrome (RTT) Natural History Study (NHS) was to examine achievement of developmental skills or abilities in classic and atypical RTT and assess phenotype-genotype relations in classic RTT., Methods: Developmental skills in four realms, gross and fine motor, and receptive and expressive communication from initial enrollment and longitudinal assessments for up to 7 years, were assessed from 542 females meeting criteria for classic RTT and 96 females with atypical RTT divided into two groups: 50 with better and 46 with poorer functional scores. Data were analyzed for age at acquisition and loss of developmental features and for phenotype-genotype effects. Acquired, lost, and retained skills were compared between classic RTT and atypical RTT with better or poorer functional scores using Fisher's Exact test. To examine if the mean total score from the Motor Behavioral Assessment during follow-up differed for acquiring a skill, we used a generalized estimating equation assuming compound symmetry correlation structure within a subject. A general linear model was used to examine whether the mean age of acquisition or loss of a developmental skill differed by mutation type. P values <0.05 were considered significant and were two-sided without adjustment for multiple testing. Statistical analyses utilized SAS 9.3 (SAS Institute, Cary, NC, USA)., Results: Early developmental skills or abilities were often acquired albeit later than normal. More complex motor and communication acquisitions were delayed or absent. Clinical severity was less in those achieving the respective skill. Individuals with R133C, R294X, and R306C point mutations and 3' truncations tended to have better developmental outcomes., Conclusions: Early developmental skills were acquired by many, but clear differences from normal emerged, particularly in skills expected after age 6 months. When comparing clinical severity, greater acquisition of specific skills was associated with specific mutations, confirming the impression that these mutations confer milder developmental abnormalities. These data may serve for planning and interpretation of early intervention studies in RTT., Trial Registration: This NHS study, clinicaltrials.gov (NCT00296764), represents the largest group of RTT participants assessed repeatedly by direct examination.

Research to quantify the potency of larval excretion/secretion from Lucilia sericata using liquid culture assays has produced contradictory results. In this study, viable counting was used to investigate the effectiveness of excretion/secretion against three marker bacterial species (Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli) and the effects of varying growing conditions in assays. Results demonstrate that factors such as number of larvae, species of bacteria and addition of nutrient influence its antibacterial potency. Therefore a standardised method should be employed for liquid culture assays when investigating the antibacterial activity of larval excretion/secretion from L. sericata., ((c) 2010 Elsevier B.V. All rights reserved.)