Expansion of the core features of VACTERL association to include genital anomalies.

Genital anomalies have been reported with VACTERL association but not considered a core feature. Acute and chronic complications stemming from unrecognized genital anomalies have been reported in adolescents and young adults with VACTERL association. We sought to determine the frequency and severity of genital anomalies in VACTERL patients and identify which core features were more frequently associated with genital anomalies. A retrospective chart review from January 2010 to October 2021 identified 211 patients with two or more core VACTERL features, 34% of whom had a genital anomaly. The majority of genital anomalies (83% of those in males and 90% in females) were classified as functionally significant (requiring surgical intervention or causing functional impairment). The frequency of genital anomalies in the VACTERL cohort was higher if anorectal malformations or renal anomalies were present in both males and females and if vertebral anomalies were present in females. Due to their functional significance, genital anomalies should be assessed in all patients with two or more core features of VACTERL association, especially in those with anorectal or renal anomalies. Most genital anomalies in males will be detected on physical examination but additional investigation is often needed to detect genital anomalies in females. The timing and type of investigation are subjects for future study.

Substantial incidence of bladder dysfunction in patients with VACTERL association: Implications for surveillance.

VACTERL association is defined as the nonrandom co-occurrence of a minimum of three of the following six key components: Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, and Limb abnormalities. Patients presenting with two components may also belong in the same spectrum. Additional components have been associated with VACTERL defects, including single umbilical artery, tethered spinal cord (TSC), and genital malformations. We observed a significant proportion of patients with bladder dysfunction (often called neurogenic bladder in the medical record) when reviewing a cohort of patients with VACTERL defects at our clinical center. Our finding calls attention to bladder dysfunction as an additional VACTERL phenotypic component. The prevalence of bladder dysfunction is greatest in those with genital anomalies, anorectal malformations, sacral dysplasia, renal anomalies, and TSC. We propose that patients with two or more VACTERL malformations be monitored for symptoms of bladder dysfunction if one or more of the identified risk factors are present until the achievement of urinary continence.

Further delineation of the CWC27-associated spliceosomeopathy: Case report and review of the literature.

Pre-mRNA splicing factors are crucial in regulating transcript diversity, by removing introns from eukaryotic transcripts, an essential step in gene expression. Splicing of pre-mRNA is catalyzed by spliceosomes. CWC27 is a cyclophilin associated with spliceosome, in which genetic defects of its components have been linked to spliceosomopathies with clinical phenotypes including skeletal developmental defects, retinitis pigmentosa (RP), short stature, skeletal anomalies, and neurological disorders. We report two siblings (male and female) of Mexican descent with a novel homozygous frameshift variant in CWC27 and aim to highlight the cardinal features among the previously described 12 cases as well as expand the currently recognized phenotypic spectrum. Both siblings presented with a range of ocular and extraocular manifestations including novel features such as solitary kidney and tarsal coalition in the male sibling, together with gait abnormalities, and Hashimoto's thyroiditis in the female sibling. Finally, we highlight ectodermal involvement including sparse scalp hair, eyebrows and lashes, pigmentary differences, nail dysplasia, and dental anomalies as a core phenotype associated with the CWC27 spliceosomopathy.

Pivoting a Community-Based Participatory Research Project for Mental Health and Immigrant Youth in Philadelphia During COVID-19.

Research has documented the need for mental health services among refugee and immigrant youth. A joint collaboration on a community-based participatory research (CBPR) research project between a university, a local art and health collective, and an immigrant and refugee organization sought to identify and understand the mental health needs and strategies for immigrant youth in Philadelphia through youth discussion and engagement in a variety of art workshops. As a result of the COVID-19 pandemic, this CBPR research project was forced to make several programmatic changes, such as shifting to a virtual setting, that impacted project implementation and intended outcomes. These changes highlight valuable lessons and practical implications in pivoting a program during COVID-19 to continue working with marginalized communities with limited resources, including barriers to technology access, at a time when effectively addressing mental health for immigrant youth has become both more challenging and pressing.

Measuring family planning norms in Zambia: A mixed methods vignette study.

Vignettes have increasingly been used in social norms research, but it is unknown whether vignettes are a valid, culturally appropriate, and effective approach for measuring family planning norms in Zambia. In this mixed methods, cross-sectional study, surveys (n = 438) and focus groups (n = 135) were conducted with married women in two, purposively selected districts in the Central Province, the rural district of Mkushi and the urban district of Kabwe. Social norms constructs measured included: reference groups, descriptive norms, injunctive norms, collective norms, and outcome expectations. Vignettes covered reaching desired family size, using modern contraception for birth spacing, and seeking family planning services. The results complemented each other suggesting vignettes may indeed be a valid approach for measuring family planning norms in this setting, although further research is needed. Successful vignette administration requires translating and back-translating, pretesting in the local language, adapting to the local context, and training. The findings hold implications for future family planning norms measurement, both in Zambia and across global settings.

Validation of a genetic risk score for atrial fibrillation: A prospective multicenter cohort study.

BACKGROUND: Atrial fibrillation (AF) is the most commonly encountered arrhythmia and is associated with an elevated risk of stroke. Improving the identification of patients with the highest risk for AF to enable appropriate surveillance and treatment, if necessary, is critical to reducing AF-associated morbidity and mortality. Multiple common single nucleotide polymorphisms (SNPs) are unequivocally associated with the lifetime risk of AF. In the current study we aimed to prospectively validate an AF genetic risk score (GRS) in previously undiagnosed patients at risk for AF. METHODS AND FINDINGS: Individuals 40 years of age or older with 1 clinical risk factor for AF, presenting with symptoms of AF, or with a first diagnosis of AF, were enrolled for genetic testing and ambulatory cardiac rhythm monitoring with an adhesive patch monitor or a long-term Holter monitor (mean wear time 10 days 21 hours and 13 days 18 hours, respectively). An AF event was the first diagnosis of AF by ECG, patch monitor, or long-term Holter monitor. The AF GRS was determined for each participant based on the weighted contribution of 12 genetic risk loci. Of 904 participants, 85 manifested AF. Their mean age was 66.2 (SD 11.8) years; 38% of participants were male. Participants in the highest quintile of AF GRS were more likely (odds ratio 3.11; 95% CI 1.27-7.58; p = 0.01) to have had an AF event than participants in the lowest quintile after adjusting for age, sex, smoking status, BMI, hypertension, diabetes mellitus, heart failure, and prior myocardial infarction. Study limitations included an ethnically homogenous population, a restricted rhythm monitoring period, and the evolving discovery of SNPs associated with AF. CONCLUSIONS: Prospective assessment of a GRS for AF identified participants with elevated risk of AF beyond established clinical criteria. Accordingly, a GRS for AF could be incorporated into overall risk assessment to better identify patients at the highest risk of developing AF, although further testing in larger populations is needed to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT01970969.

Instagram Users' Experiences of Miscarriage.

OBJECTIVE: To explore the shared experiences of miscarriage using a qualitative analysis of social media posts on Instagram. METHODS: We performed this qualitative study by collecting text, photos, hashtags, and emoji from 200 Instagram posts on five arbitrarily selected days in 2019. Key eligibility criteria included posts that described a personal experience of miscarriage and that used the hashtag #ihadamiscarriage. Through directed content analysis, our multidisciplinary team conducted open coding to identify common topics in the data, developed a code book, and coded all posts. Twenty-five percent of posts were double-coded by two team members and analyzed for agreement. The codes were organized into overarching themes. RESULTS: Intercoder reliability was excellent (kappa 0.95). Themes included medical and physical experiences of miscarriage, social experiences of miscarriage, the emotional spectrum of experiencing a miscarriage, family identity and the effects of miscarriage, and mechanisms of processing and coping through a miscarriage. We observed complex and often conflicted emotional states and noted that the effects of miscarriage were felt for months and years by many Instagram users. Use of social media and disclosure of miscarriage was a source of coping for many users. CONCLUSION: Women post about their miscarriages on social media for a variety of reasons, especially to find support and community and to help break the silence around miscarriage. Health care providers may consider discussing use of this platform as a support and coping mechanism in the setting of pregnancy loss.