Identification of an ADAMTS2 frameshift variant in a cat family with Ehlers-Danlos syndrome.

We investigated 4 European domestic shorthair kittens with skin lesions consistent with the dermatosparaxis type of the Ehlers-Danlos syndrome, a connective tissue disorder. The kittens were sired by the same tomcat but were born by 3 different mothers. The kittens had easily torn skin resulting in nonhealing skin wounds. Both clinically and histologically, the skin showed thin epidermis in addition to inflammatory changes. Changes in collagen fibers were visible in electron micrographs. The complete genome of an affected kitten was sequenced. A one base pair duplication leading to a frameshift in the candidate gene ADAMTS2 was identified, p.(Ser235fs*3). All 4 affected cats carried the frameshift duplication in a homozygous state. Genotypes at this variant showed perfect cosegregation with the autosomal recessive Ehlers-Danlos syndrome phenotype in the available family. The mutant allele did not occur in 48 unrelated control cats. ADAMTS2 loss-of-function variants cause autosomal recessive forms of Ehlers-Danlos syndrome in humans, mice, dogs, cattle, and sheep. The available evidence from our investigation together with the functional knowledge on ADAMTS2 in other species allows to classify the identified ADAMTS2 variant as pathogenic and most likely causative variant for the observed Ehlers-Danlos syndrome.

Patient Perspectives on the COVID-19 Vaccine: A Pilot Survey Study of Patients in Endocrinology Clinics.

OBJECTIVE: Vaccine hesitancy is an impediment to fighting the COVID-19 pandemic. Endocrinology clinics routinely see patients who are at high risk of a more aggressive form of COVID-19, including patients with diabetes, obesity, and hypertension. As patients with endocrine-related conditions often require multiple visits each year, endocrinology clinics provide a significant opportunity for vaccine education. The aim of our study was to evaluate patient perspectives about COVID-19 vaccination in outpatient endocrinology clinics. METHODS: A pilot survey study of patients who visited 3 endocrinology clinics between May 31, 2021, and June 18, 2021. A 7-item questionnaire explored the patients' perspectives and behaviors regarding COVID-19 vaccination. Data were analyzed with descriptive statistics. RESULTS: A total of 446 patients from 3 clinic locations (1 urban and 2 suburbans) completed our survey. There were 361 (81%) patients who indicated that they were planning to or had already received the COVID-19 vaccination, 56 (13%) reported no intent for vaccination, and 29 (7%) were unsure. Of the 85 patients who were unsure or did not intend to be vaccinated, 43 (51%) were Black, 30 (35%) were White, and 4 (5%) had other racial/ethnic identities. When asked about vaccine hesitancy, 25 (29%) wanted to wait and see how the others responded to the vaccine, 20 (24%) had concerns about the side effects, 12 (14%) did not believe in vaccines, and 11 (13%) felt that COVID-19 was not as bad as the media had portrayed it. Significantly more Black patients had vaccine hesitancy than White patients (P = .035). CONCLUSION: Although most endocrinology patients were amenable to COVID-19 vaccination, a subpopulation still expressed vaccine hesitancy, indicating that endocrinology clinics may be an ideal place for targeted vaccine education.

The Complex and Diverse Genetic Architecture of the Absence of Horns (Polledness) in Domestic Ruminants, including Goats and Sheep.

Horns are the most obvious common feature of Bovidae. The naturally occurring absence of horns in these species, also known as polledness, is of surprisingly heterogeneous nature, although they are Mendelian traits. This review compares in detail the molecular differences among the causes of inherited polledness in the domestic ruminant species of cattle, yak, sheep, and goat based on the causal gene variants that have been discovered in recent years. The genetic causes for the lack of horns in small ruminants seem not only to be more complex, e.g., in sheep, breed-specific characteristics are still unexplained, but in goats, there is also the associated disorder of intersexuality-polled intersex syndrome (PIS). In connection with animal welfare and the associated discussion about a legal ban on the dehorning of all farm animals, naturally hornless animals and the causal genetic variants are of increasing research interest in the age of genome editing. However, the low acceptance of genetic engineering in livestock, especially in European societies, limits its use in food-producing animals. Therefore, genotype-based targeted selection of naturally occurring variants is still a widely used method for spreading this desired trait within and across populations, at least in cattle and sheep.

Capturing Genetic Diversity and Selection Signatures of the Endangered Kosovar Balusha Sheep Breed.

There is a growing concern about the loss of animal genetic resources. The aim of this study was to analyze the genetic diversity and potential peculiarity of the endangered Kosovar sheep breed Balusha. For this purpose, a dataset consisting of medium-density SNP chip genotypes (39,879 SNPs) from 45 Balusha sheep was generated and compared with SNP chip genotypes from 29 individuals of a second Kosovar breed, Bardhoka. Publicly available SNP genotypes from 39 individuals of the relatively closely located sheep breeds Istrian Pramenka and Ruda were additionally included in the analyses. Analysis of heterozygosity, allelic richness and effective population size was used to assess the genetic diversity. Inbreeding was evaluated using two different methods (FIS, FROH). The standardized FST (di) and cross-population extended haplotype homozygosity (XPEHH) methods were used to detect signatures of selection. We observed the lowest heterozygosity (HO = 0.351) and effective population size (Ne5 = 25, Ne50 = 228) for the Balusha breed. The mean allelic richness levels (1.780-1.876) across all analyzed breeds were similar and also comparable with those in worldwide breeds. FROH estimates (0.023-0.077) were highest for the Balusha population, although evidence of decreased inbreeding was observed in FIS results for the Balusha breed. Two Gene Ontology (GO) TERMs were strongly enriched for Balusha, and involved genes belonging to the melanogenesis and T cell receptor signaling pathways, respectively. This could result from selection for the special coat color pattern of Balusha (black head) and resistance to certain infectious diseases. The analyzed diversity parameters highlight the urgency to preserve the local Kosovar Balusha sheep as it is clearly distinguished from other sheep of Southeastern Europe, has the lowest diversity level and may harbor valuable genetic variants, e.g., for resistance to infectious diseases.

Applicability of the GAIA Maternal and Neonatal Outcome Case Definitions for the Evaluation of Adverse Events Following Vaccination in Pregnancy in High-income Countries.

BACKGROUND: The Brighton Collaboration Global Alignment of Immunization Safety in Pregnancy (GAIA) project developed case definitions for the assessment of adverse events in mothers and infants following maternal immunization. This study evaluated the applicability of these definitions to data collected in routine clinical care and research trial records across 7 sites in high-resource settings. METHODS: Data collection forms were designed and used to retrospectively abstract the key elements of the GAIA definitions from records for 5 neonatal and 5 maternal outcomes, as well as gestational age. Level of diagnostic certainty was assessed by the data abstractor and an independent clinician, and then verified by Automated Brighton Case logic. The ability to assign a level of diagnostic certainty for each outcome and the positive predictive value (PPV) for their respective ICD-10 codes were evaluated. RESULTS: Data from 1248 case records were abstracted: 624 neonatal and 622 maternal. Neonatal outcomes were most likely to be assessable and assigned by the level of diagnostic certainty. PPV for preterm birth, low birth weight, small for gestational age and respiratory distress were all above 75%. Maternal outcomes for preeclampsia and fetal growth restriction showed PPV over 80%. However, microcephaly (neonatal outcome) and dysfunctional labor (maternal outcome) were often nonassessable, with low PPVs. CONCLUSIONS: The applicability of GAIA case definitions to retrospectively ascertain and classify maternal and neonatal outcomes was variable among sites in high-resource settings. The implementation of the case definitions is largely dependent on the type and quality of documentation in clinical and research records in both high- and low-resource settings. While designed for use in the prospective evaluation of maternal vaccine safety, the GAIA case definitions would likely need to be specifically adapted for observational studies using alternative sources of data, linking various data sources and allowing flexibility in the ascertainment of the elements and levels of certainty of the case definition.

Parenting with a disability: exploring the satisfaction and efficacy of the PediaLift wheelchair accessible crib.

PURPOSE: Parents with disabilities face many challenges in fulfilling their daily roles. Previous literature has shown that assistive technology (AT) can be a viable solution to help an individual with a disability participate in everyday roles. Although AT can increase ability of parents with disabilities to care for their children, there are many barriers that prevent them from getting the AT that they need. Some of these barriers include a lack of training and awareness by healthcare providers regarding AT options, a lack of rehabilitation therapists' feeling they are competent to provide AT options for their clients. and funding barriers. One issue that impacts the ability to get funding for AT is the lack of research supporting the efficacy of the technology. An AT device specifically designed for parents with disabilities is an adaptive crib called PediaLift. Health insurance companies are resistant to funding the PediaLift stating that there is no evidence in the literature to support its efficacy. MATERIALS AND METHODS: In this study, we investigated the efficacy of the Pedialift crib by using the Quebec User Evaluation of Satisfaction with Assistive Technology 2.0 (QUEST 2.0) survey and the Canadian Occupational Performance Measure (COPM) with individuals who have already purchased and used the device. RESULTS: Findings revealed that overall users were satisfied with the device and services provided. CONCLUSION: Participants were more able to participate in the role of parenting after obtaining the Pedialift.

Hepatic Complications in Preeclampsia.

In cases of preeclampsia with severe features and hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome, hepatic complications portend significant short-term and long-term maternal health implications. In this section, we will discuss the physiology of normal hepatic function in pregnancy, the pathophysiology of the abnormalities noted in hepatic function during the process of preeclampsia development, the diagnosis and management of preeclampsia, imitators of HELLP syndrome, the utility of various biomarkers in the diagnosis and prognosis of the preeclampsia disease spectrum, possible underlying genetic factors predisposing women to developing hepatic abnormalities with preeclampsia, and finally prognosis and management of a subcapsular hematoma.

Pheochromocytoma-Induced Takotsubo Cardiomyopathy.

Pheochromocytoma, a rare catecholamine-secreting tumor, typically manifests itself with paroxysmal hypertension, tachycardia, headache, and diaphoresis. Less often, symptoms related to substantial hemodynamic compromise and cardiogenic shock occur. We report the case of a 66-year-old woman who presented with abdominal pain. Examination revealed a large right adrenal mass, cardiogenic shock, and severe heart failure in the presence of normal coronary arteries. Within days, the patient's hemodynamic status and left ventricular ejection fraction improved markedly. Results of imaging and biochemical tests confirmed the diagnosis of pheochromocytoma-induced takotsubo cardiomyopathy. Medical therapy and right adrenalectomy resolved the patient's heart failure, and she was asymptomatic postoperatively. We recommend awareness of the link between pheochromocytoma and takotsubo cardiomyopathy, and we discuss relevant diagnostic and management principles.

Developmental functioning and symptom severity influence age of diagnosis in Canadian preschool children with autism.

BACKGROUND: Early diagnosis of autism spectrum disorder (ASD) is essential in most Canadian jurisdictions to access interventions that improve long-term child outcomes. Our main objective was to identify factors associated with timing of ASD diagnosis in five provinces across Canada. METHODS: Factors influencing age of diagnosis were assessed in the analyses of an inception cohort of children diagnosed with ASD between ages 2 and 5 years. We examined bivariate associations and using a series of multiple variable regression models, evaluated the unique contributions of developmental functioning, ASD symptoms and demographic variables. Children with known genetic abnormalities, or severe sensory or motor impairments interfering with assessment were excluded. RESULTS: Participants were 421 children (84.6% boys). The mean age of diagnosis was 38.2 months (SD=8.7), an average of 19 months after parents identified initial concerns. Factors associated with later diagnosis included more advanced language and cognitive skills, and higher levels of restricted repetitive behaviour symptoms. Child sex and family demographics were not associated with age of diagnosis. In regression analyses, language and cognitive skills accounted for 6.8% of variance in age of diagnosis and ASD symptoms contributed an additional 5.5%. Provincial site accounted for 4.0% of variance in age of diagnosis, independent of developmental skills and ASD symptoms. INTERPRETATION: Diagnosis of ASD occurred, on average, 19 months after parents' initial concerns. Language and cognitive skills, symptom severity and provincial site accounted for variation in age of ASD diagnosis in this Canadian cohort. Variable presentation across the developmental continuum must be considered in planning assessment services to ensure timely ASD diagnosis so that outcomes can be improved. Policy and practice leadership is also needed to reduce interprovincial variability.

Bromocriptine Use in Peripartum Cardiomyopathy: Review of Cases.

Objective This study is to review published cases of peripartum cardiomyopathy (PPCM) treated with bromocriptine and outline pros and cons of the treatment strategy. Data Sources Data were collected from PubMed/MedLine, ClinicalTrials.gov; the years 2007 to 2018 were searched for English-language articles. Search terms: "bromocriptine and peripartum cardiomyopathy", "bromocriptine and cardiomyopathy." Methods of Study Selection This search strategy yielded 171 articles. After excluding duplicates, 86 studies were reviewed. Sixty-one articles involving the treatment of PPCMP were included, and of these, 17 were case reports of patients with PPCMP treated with bromocriptine; these studies were included in this review. Tabulation, Integration, and Results Seventeen of these articles were case reports of patients with peripartum cardiomyopathy treated with bromocriptine that were included. Conclusion Bromocriptine seems to be a promising treatment, there is currently insufficient evidence for universal utilization of bromocriptine for all patients with PPCMP. Addition of bromocriptine to the standard heart failure therapy should be individualized.

Physical Therapists' Use and Alteration of Standardized Assessments of Motor Function in Children.

PURPOSE: This study presents survey responses of pediatric physical therapists' use and alteration of standardized assessments of motor function in children aged 2 to 10 years. METHODS: Electronic and paper surveys were distributed to practicing physical therapists through the APTA Academy of Pediatric Physical Therapy electronic newsletter and 2 national conferences. Data were analyzed by response frequencies, qualitative responses, and χ(2) analyses for demographic characteristics. RESULTS: A total of 497 pediatric physical therapists responded. Most (93%) reported using standardized assessments, with the majority (84%) reporting the normative scores. Almost all respondents (94%) also reported that they at least occasionally modify assessments. CONCLUSION: Standardized assessments are used by most therapists, but the high use of modifications during testing is concerning. Survey reports from therapists indicate a disconnect between standardized assessments and the needs of the child, leaving clinicians working to report required scores while maintaining validity of testing procedures.

PROVIDER PRACTICE HABITS AND BARRIERS TO CARE IN OBESITY MANAGEMENT IN A LARGE MULTICENTER HEALTH SYSTEM.

OBJECTIVE: To identify provider recommendations and barriers in obesity management in a multicenter academic health system with extensive weight-loss management resources. METHODS: A 26-question online survey was sent to attending physicians, trainees, and advanced practice providers in primary care specialties (internal medicine, family medicine, women's health) and endocrinology. RESULTS: The survey response rate was 26% (111/430). Of respondents, 50% were internal medicine, 24% family medicine, 16% women's health, and 9% endocrinology. The majority were attending physicians (54%) and residents (40%). About 50% of respondents advised weight loss for a body mass index (BMI) >30 kg/m2 in >50% of clinic visits. Limited time (82%) was the most common reason for not discussing weight loss, followed by the perception that discussion would not change patient behavior, insufficient knowledge, and discomfort broaching the subject. Common barriers to prescribing anti-obesity medications included limited experience (57%) and concern for adverse reactions (26%). Only 44% offered bariatric surgery to >50% of their patients who met criteria. Primary reasons for not referring included concerns of high surgical risk from comorbidities (57%) and potential adverse events (32%). Endocrinology had the highest referral to surgery. Attending physicians and fellows were more likely than residents to advise weight loss at lower BMI, offer medications, and refer to bariatric surgery. CONCLUSION: Our study reveals reluctance and lack of primary care confidence in managing obesity with pharmacotherapy and bariatric surgery, especially in the earlier stages of obesity. Barriers to care include lack of clinic time, limited experience, and concerns about treatment risks. ABBREVIATIONS: BMI = body mass index; HbA1c = hemoglobin A1c; IRB = Institutional Review Board.

Mobile Application Use Among Obstetrics and Gynecology Residents.

BACKGROUND: Mobile applications (apps) are increasingly used in clinical settings, particularly among resident physicians. Apps available to patients and physicians are rapidly expanding. OBJECTIVE: We aimed to describe obstetrics and gynecology (ob-gyn) residents' use of and attitudes toward ob-gyn-related mobile apps. METHODS: We conducted a cross-sectional survey of residents at all 19 California ob-gyn programs using a web-based questionnaire. Responses were analyzed using descriptive and chi-square statistics. RESULTS: Of 386 residents contacted, 197 (51%) completed the survey. All respondents owned mobile devices (100% smartphone, 74% tablet), and 93% used apps in the clinical setting. Commonly used ob-gyn-related apps were pregnancy wheels (84%), cervical cancer screening algorithms (68%), and contraceptive eligibility guidelines (47%). Only 53% of respondents recommended apps to patients, with many reporting not being aware of appropriate apps. Sixty-two percent of respondents used apps for learning, but only 3 ob-gyn-specific apps were mentioned. Most chose apps based on recommendations from other residents. Residents viewed mobile technology as an important clinical tool (92%) that improves efficiency (89%). App use did not differ by gender, age, or postgraduate year. CONCLUSIONS: Mobile technology and ob-gyn-related app use are widely used among California ob-gyn residents, who feel that apps enhance their ability to care for patients. Context of app use varies, with most residents using apps during clinical care, but only half recommending apps to patients. Recommendations from other residents are the common resource for discovering new apps, suggesting a need for more formal guidance on finding and evaluating apps.

Valuable occupational therapy fieldwork educator behaviors.

OBJECTIVE: The purpose of this study was to investigate fieldwork educator behaviors that are valuable from the perspective of Level II occupational therapy and occupational therapist assistant students and fieldwork educators. PARTICIPANTS: 85 fieldwork educators and 37 students from Eastern and Western parts of the United States. METHODS: The 5 competency categories of the Self Assessment Tool for Fieldwork Educator Competency were used as the basis for developing the survey items and data was analyzed with non-parametric statistics to check for differences among groups of respondents. RESULTS: Students and fieldwork educators generally ranked the value of the behaviors in the survey as the same. There were differences noted between responses of level II students on first, second, and third placements regarding supervision behaviors of fieldwork educators. (Chi square=6.59, p=0.04 and Chi square=7.95, p=0.02). CONCLUSION: The alignment of opinion of students and fieldwork educators is important in that it reinforces the common goal of academic programs, students, and fieldwork educators. More research needs to be done in order to understand the impact of placement order on the rankings of valued fieldwork educator behaviors.

Donor families, distinctive secondary losses, and "second death" experiences.

Communication between donor families and the recipients of their loved ones' organs and tissues is a relatively new area of study. The National Kidney Foundation founded the National Donor Family Council in 1992 as a home for donor families. One of several items addressed by the Council was guidelines for communication, supporting the rights of donor families and recipients to communicate and build relationships should they choose to do so. Donation and transplant agencies play a strong role in facilitating and supporting donor families and recipients with these unique new relationships. This article offers 3 case examples of distinctive secondary losses and "second death" experiences encountered by some donor family members when the donation of tissues or organs they have authorized could not be used for transplantation, when those grafts fail or are rejected, or when the recipient dies. On that basis, the article explores the nature of these experiences and some reasons why they occur. Initial recommendations about how to address these experiences are provided. Finally, a 4-part agenda is suggested for research about (1) the nature of these distinctive secondary loss and second death experiences encountered by some donor families; (2) communications between donation and transplant professionals, on the one hand, and potential and actual donor family members, on the other hand; (3) the education, training, and support of professionals who provide bereavement support to donor family members; and (4) a review of the National Communication Guidelines.