Loss of function of FAM177A1, a Golgi complex localized protein, causes a novel neurodevelopmental disorder.

PURPOSE: The function of FAM177A1 and its relationship to human disease is largely unknown. Recent studies have demonstrated FAM177A1 to be a critical immune-associated gene. One previous case study has linked FAM177A1 to a neurodevelopmental disorder in four siblings. METHODS: We identified five individuals from three unrelated families with biallelic variants in FAM177A1. The physiological function of FAM177A1 was studied in a zebrafish model organism and human cell lines with loss-of-function variants similar to the affected cohort. RESULTS: These individuals share a characteristic phenotype defined by macrocephaly, global developmental delay, intellectual disability, seizures, behavioral abnormalities, hypotonia, and gait disturbance. We show that FAM177A1 localizes to the Golgi complex in mammalian and zebrafish cells. Intersection of the RNA-seq and metabolomic datasets from FAM177A1-deficient human fibroblasts and whole zebrafish larvae demonstrated dysregulation of pathways associated with apoptosis, inflammation, and negative regulation of cell proliferation. CONCLUSION: Our data sheds light on the emerging function of FAM177A1 and defines FAM177A1-related neurodevelopmental disorder as a new clinical entity.

A Case of Congenital Hypotonia and Developmental Delay in an Individual with a De Novo Variant Outside of the Canonical HX-Motif of ATN1.

We present a case of a 4-year-old female with a de novo heterozygous variant in the ATN1 gene. The whole exome sequencing was performed on the patient and her parents, and a likely pathogenic, de novo variant was identified in exon 5 of the ATN1 gene. There are two well-documented conditions associated with the ATN1 gene: congenital hypotonia, epilepsy, developmental delay, and digital anomalies (CHEDDA) syndrome and dentatorubral-pallidoluysian atrophy (DRPLA). Unlike DRPLA which is caused by an expanded trinucleotide repeat, CHEDDA syndrome is caused by variants in the histidine-rich (HX) motif at exon 7 of ATN1 similar to the de novo variant found in exon 5 of the presented individual. CHEDDA syndrome is a neurodevelopmental disorder previously documented in over 17 unrelated individuals. Compared to other documented CHEDDA syndrome cases, this individual shares similarities in respect to hypotonia, hearing impairment, impaired gross and fine motor ability, gastrointestinal abnormalities, hyperextensible joints, and frontal bossing. However, the individual presented here has only a moderate developmental delay and has acquired more developmental milestones such as higher-level language skills and more developed fine motor skills, than previously described individuals. The authors of this paper believe the patient's milder phenotype may be due to the variant's location outside of the canonic HX motif.

Case report of atypical Leigh syndrome in an adolescent male with novel biallelic variants in NDUFAF5 and review of the natural history of NDUFAF5-related disorders.

NDUFAF5 encodes a Complex I assembly factor which is critical to the modification of a core subunit, NDUFS7, in early Complex I factor assembly. Mutations in NDUFAF5 have been previously shown to cause Complex I deficiency leading to mitochondrial respiratory chain impairment. More than 15 individuals affected by variants in NDUFAF5 have been described; however, there is phenotypic heterogeneity within this cohort. Some individuals display features of classical Leigh syndrome with early onset neurodegeneration whereas others live into early adulthood with progressive neurological deficits. Here, we present a clinical report of a 17-year-old African American individual with compound heterozygous mutations in NDUFAF5. The individual presented with childhood onset bilateral optic atrophy and developed progressive neuromuscular decline with relatively preserved cognition over time.

Descriptive Analysis of Orthopaedic Surgery Residency Program Directors.

The purpose of this study was to analyze the demographics and backgrounds of U.S. orthopaedic surgery residency program directors (PDs). We collected publicly available information on 189 orthopaedic surgery residency PDs. Of those PDs, 90% were male MDs with an average age of 52. The average age at PD appointment was 45. The average duration of appointment was 7 years. About 81% of programs were university-affiliated, and 61% were in an urban environment. PDs attended 100 medical schools, 129 residencies, and 96 fellowships. of PDs, 87% completed fellowships, commonly in trauma and sports medicine. There was no significant difference between male and female PDs when comparing age, academic appointment, or urban/rural environment. Most female PDs (89%) were at university-based hospitals. Of PDs at osteopathic-focused programs, 28% had an MD/PD. No program with an allopathic focus had a DO/PD. Lastly, 38% of PDs worked at the center where they completed residency. (Journal of Surgical Orthopaedic Advances 31(4):252-255, 2022).

Efficacy of a student-led community contact tracing program partnered with an academic medical center during the coronavirus disease 2019 pandemic.

PURPOSE: Contact tracing has proven successful at controlling coronavirus 2019 (COVID-19) globally, and the Center for Health Security has recommended that the United States add 100,000 contact tracers to the current workforce. METHODS: To address gaps in local contact tracing, health professional students partnered with their academic institution to conduct contact tracing for all COVID-19 cases diagnosed onsite, which included identifying and reaching their contacts, educating participants, and providing social resources to support effective quarantine and isolation. RESULTS: From March 24 to May 28, 536 laboratory-confirmed COVID-19 cases were contacted and reported an average of 2.6 contacts. Contacts were informed of their exposure, asked to quarantine, and monitored for the onset of symptoms. Callers reached 94% of cases and 84% of contacts. Seventy-four percent of cases reported at least one contact. Household members had higher rates of reporting symptoms (odds ratio, 1.65; 95% confidence interval, 1.19-2.28). The average test turnaround time decreased from 21.8 days for the first patients of this program to 2.3 days on the eleventh week. CONCLUSIONS: This provides evidence for the untapped potential of community contact tracing to respond to regional needs, confront barriers to effective quarantine, and mitigate the spread of COVID-19.

Implementation and Process of a COVID-19 Contact Tracing Initiative: Leveraging Health Professional Students to Extend the Workforce During a Pandemic.

BACKGROUND: The Centers for Disease Control and Prevention recommends aggressive contact tracing to control the COVID-19 pandemic. In this work, we (1) describe the development of a COVID-19 contact tracing initiative that includes medical, nursing, and public health students, and is led by clinicians and infectious disease epidemiologists within our health system, and, (2) articulate process steps for contact tracing including workflows and telephone scripts, and, (3) highlight the key challenges and strategies to overcome these challenges. METHODS: A single academic institution-based contact tracing initiative was rapidly scaled to 110 health professional students, four physicians, two epidemiologists, and a research team. Following training, students called patients who were COVID-19 positive and the individuals they were in contact with to ensure proper isolation and quarantine measures. Students also assisted those who faced barriers to quarantine. IMPLICATIONS: In total, between March 24 and May 28 - this initiative completed contact tracing for 536 confirmed cases, which resulted in the identification of 953 contacts. We aim to disseminate this process, including telephone scripts and workflow, to other health systems for use in their initiatives to respond to the COVID-19 pandemic and future public health emergencies.

Mode of first delivery and postpartum weight retention at 1 year.

BACKGROUND: The prevalence of obesity in the US has increased markedly in women in their reproductive years over the past 3 decades, partially due to higher rates of postpartum weight retention. This was a prospective cohort study that investigated mode of delivery as an independent risk factor for postpartum weight retention at 1 year postpartum. METHODS: Data from 2500 first-time mothers, aged 18-35 with singleton pregnancies were included in this analysis. Postpartum weight retention was measured at 1 year after delivery and was defined as weight at 1 year compared to weight just before becoming pregnant. Logistic regression models assessed the association between mode of first delivery and subsequent weight retention of 10 pounds or more, adjusting for key confounders including pre-pregnancy body mass index, gestational weight gain, age, education, poverty status, smoking, race/ethnicity, gestational age, pregnancy complications, breastfeeding and exercise habits during pregnancy and in the first year after delivery. RESULTS: At 12 months after delivery the women who had delivered by cesarean were more likely to have a postpartum weight retention of 10 pounds or more (27.9%), than those who had delivered vaginally (22.2%), unadjusted OR 1.35 (95% CI 1.11-1.65, p=.003). Even after controlling for confounding variables, mode of delivery remained significantly associated with postpartum weight retention of 10 pounds or more, adjusted OR 1.30 (95% CI 1.04-1.62, p=.02). CONCLUSIONS: Cesarean delivery at first childbirth is associated with increased risk of weight retention of 10 pounds or more at 1 year postpartum.