Impact of a Mentorship Program to Prepare Medical Students for the Military Residency Match.

INTRODUCTION: Mentorship programs have well-documented benefits to both mentees and mentors. Military medical students face unique challenges in medical school given their service-specific requirements and separate military match process. We therefore aimed to determine whether military medical students' participation in a mentorship program impacts their confidence in applying to obstetrics and gynecology (OB/GYN) residency. MATERIALS AND METHODS: First, a needs assessment survey regarding the use of a mentorship program was sent to medical students, residents, fellows, and attendings. A structured mentorship program was then developed for military medical students applying to OB/GYN residency based on the survey results. Mentors were randomly paired with mentees and asked to appraise curriculum vitaes, review personal statements, and perform mock interviews. Following completion of these activities, participants were sent a post-intervention questionnaire. This project was exempt by our institution's Institutional Review Board. RESULTS: Our program had 56 participants, with 29 individuals completing our post-intervention survey (response rate 51.8%). After participating in the program, 92.3% of mentors stated they plan to continue a relationship with their mentee. All the mentee respondents stated they would participate in this program again. Before participating in the program, 16.7% of mentees felt "prepared" or "extremely prepared" for the match, compared to 87.6% post-intervention. Most mentee respondents (75%) reported that this program made them a more competitive applicant. Following the mentorship program, 66.7% of participants successfully matched into OB/GYN residency. CONCLUSIONS: This reproducible, well-received intervention can be implemented to facilitate mentoring connections regardless of geographic location. As the OB/GYN specialty develops its own application process, civilian medical schools should consider adopting similar programs to aid their students in navigating the match process.

Effect of sterile vs clean gloves for cervical checks in labor on maternal infection at term: a randomized trial.

BACKGROUND: Intrapartum infection usually warrants immediate delivery and impacts 5-12% of term pregnancies, with the most commonly identified pathogenic organism being of the Ureaplasma genus. When performing cervical examinations during labor, providers in the United States commonly use sterile gloves, although there are no data currently to support that this practice reduces rates of infection. Furthermore, in nearly all other settings of Gynecologic care, aside from surgery in an operating room, nonsterile gloves are used. Even though the uterus could be sterile in normal pregnancies, the provider performing the cervical examination must traverse the milieu of vaginal bacteria in order to reach the cervix to perform the exam, introducing vaginal microbiota into the uterus regardless of the type of glove used. This prospective randomized controlled study examines whether the type of glove used (sterile vs clean) impacts the rates of intrapartum infection in patients receiving cervical examinations during labor or induction of labor at term.. OBJECTIVE: This study aimed to evaluate if the glove type (sterile vs clean) used for cervical examinations during labor affects the rates of intrapartum and postpartum infection. STUDY DESIGN: This randomized controlled trial assigned eligible and consenting participants to receive cervical examinations during labor with either sterile powder-free polyvinyl chloride examination gloves (current routine practice, control group) or clean powder-free nitrile examination gloves (nonsterile, experimental group). The primary outcome was rates of intrapartum infection (chorioamnionitis). Sample size calculations estimated that 300 participants would be needed with a rate of infection of 10% in the control group and 20% in the experimental group to demonstrate difference between the groups; however, the rates of infection were much lower than expected, at 5.4% and 4.4% in the sterile and clean glove group, respectively. At this point, it was determined futile to continue the study because a sample size of >29,000 participants would be needed, which would not be achievable at a single tertiary care referral center with approximately 3500 deliveries per year. The study was approved by the Eastern Virginia Medical School Institutional Review Board (IRB 21-09-FB-0206), and was registered at ClinicalTrials.gov (identifier NCT05603624; https://clinicaltrials.gov/ct2/show/NCT05603624). RESULTS: A total of 163 participants with singleton pregnancies completed the study; 74 (45%) were randomized to the sterile glove group, and 89 (55%) were randomized to the clean glove group. In the sterile glove group, 4 (5.4%) developed intrapartum infection (chorioamnionitis) and 1 (1.3%) developed postpartum infection (endometritis). In the clean glove group, 4 (4.4%) developed intrapartum infection and 2 (2.2%) developed postpartum infection. There was no significant difference in rates of intrapartum infection (P=1.0) or postpartum infection (P=1.0), or combined rates of infection (including both chorioamnionitis and endometritis; P=.99) between the sterile and the clean glove group. When comparing the participants from both groups who had any intrapartum or postpartum infection (n=11) with those who had no infection (n=152), the former were more likely to be nulliparous (P=.01), have lower gravidity (P<.01) and parity (P<.01), have longer times from first cervical examination to delivery (P=.02), have longer times from rupture of membranes to delivery (P=.0001), undergo cesarean delivery (P=.0002), and experience postpartum hemorrhage (P=.001). Although participants who were in labor for a longer time also likely had more cervical examinations, these data could suggest that duration of labor (P=.02) is more closely associated with infectious morbidity compared with the number of cervical examinations (P=.15). CONCLUSION: Using clean gloves for cervical examinations during labor is unlikely to increase risk of infection, and could reduce cost by up to 92.4% at our institution, saving over $25,000 annually.

Targeted Augmentation of Nuclear Gene Output (TANGO) of Scn1a rescues parvalbumin interneuron excitability and reduces seizures in a mouse model of Dravet Syndrome.

Dravet Syndrome (DS) is a severe developmental and epileptic encephalopathy typically caused by loss-of-function de novo mutations in the SCN1A gene which encodes the voltage-gated sodium channel isoform NaV1.1. Decreased NaV1.1 expression results in impaired excitability of inhibitory interneurons and seizure onset. To date, there are no clinically available treatments for DS that directly address the core mechanism of disease; reduced NaV1.1 expression levels in interneurons. Recently, Targeted Augmentation of Nuclear Gene Output (TANGO) of SCN1A by the antisense oligonucleotide (ASO) STK-001, was shown to increase Scn1a mRNA levels, increase NaV1.1 protein expression, reduce seizures, and improve survival in the Scn1a+/- mouse model of DS. However, it remains unknown whether STK-001 treatment rescues the reduced intrinsic excitability of parvalbumin-positive (PV) inhibitory interneurons associated with DS. In this study, we demonstrate that STK-001 treatment reduces seizures, prolongs survival, and rescues PV interneuron excitability in Scn1a+/- mice to levels observed in WT littermates. Together, these results support the notion that TANGO-mediated augmentation of NaV1.1 levels directly targets and rescues one of the core disease mechanisms of DS.

Somatostatin-Positive Interneurons Contribute to Seizures in SCN8A Epileptic Encephalopathy.

SCN8A epileptic encephalopathy is a devastating epilepsy syndrome caused by mutant SCN8A, which encodes the voltage-gated sodium channel NaV1.6. To date, it is unclear if and how inhibitory interneurons, which express NaV1.6, influence disease pathology. Using both sexes of a transgenic mouse model of SCN8A epileptic encephalopathy, we found that selective expression of the R1872W SCN8A mutation in somatostatin (SST) interneurons was sufficient to convey susceptibility to audiogenic seizures. Patch-clamp electrophysiology experiments revealed that SST interneurons from mutant mice were hyperexcitable but hypersensitive to action potential failure via depolarization block under normal and seizure-like conditions. Remarkably, GqDREADD-mediated activation of WT SST interneurons resulted in prolonged electrographic seizures and was accompanied by SST hyperexcitability and depolarization block. Aberrantly large persistent sodium currents, a hallmark of SCN8A mutations, were observed and were found to contribute directly to aberrant SST physiology in computational modeling and pharmacological experiments. These novel findings demonstrate a critical and previously unidentified contribution of SST interneurons to seizure generation not only in SCN8A epileptic encephalopathy, but epilepsy in general.SIGNIFICANCE STATEMENTSCN8A epileptic encephalopathy is a devastating neurological disorder that results from de novo mutations in the sodium channel isoform Nav1.6. Inhibitory neurons express NaV1.6, yet their contribution to seizure generation in SCN8A epileptic encephalopathy has not been determined. We show that mice expressing a human-derived SCN8A variant (R1872W) selectively in somatostatin (SST) interneurons have audiogenic seizures. Physiological recordings from SST interneurons show that SCN8A mutations lead to an elevated persistent sodium current which drives initial hyperexcitability, followed by premature action potential failure because of depolarization block. Furthermore, chemogenetic activation of WT SST interneurons leads to audiogenic seizure activity. These findings provide new insight into the importance of SST inhibitory interneurons in seizure initiation, not only in SCN8A epileptic encephalopathy, but for epilepsy broadly.

Biallelic inherited SCN8A variants, a rare cause of SCN8A-related developmental and epileptic encephalopathy.

OBJECTIVE: Monoallelic de novo gain-of-function variants in the voltage-gated sodium channel SCN8A are one of the recurrent causes of severe developmental and epileptic encephalopathy (DEE). In addition, a small number of de novo or inherited monoallelic loss-of-function variants have been found in patients with intellectual disability, autism spectrum disorder, or movement disorders. Inherited monoallelic variants causing either gain or loss-of-function are also associated with less severe conditions such as benign familial infantile seizures and isolated movement disorders. In all three categories, the affected individuals are heterozygous for a SCN8A variant in combination with a wild-type allele. In the present study, we describe two unusual families with severely affected individuals who inherited biallelic variants of SCN8A. METHODS: We identified two families with biallelic SCN8A variants by diagnostic gene panel sequencing. Functional analysis of the variants was performed using voltage clamp recordings from transfected ND7/23 cells. RESULTS: We identified three probands from two unrelated families with DEE due to biallelic SCN8A variants. Each parent of an affected individual carried a single heterozygous SCN8A variant and exhibited mild cognitive impairment without seizures. In both families, functional analysis demonstrated segregation of one allele with complete loss-of-function, and one allele with altered biophysical properties consistent with partial loss-of-function. SIGNIFICANCE: These studies demonstrate that SCN8A DEE may, in rare cases, result from inheritance of two variants, both of which exhibit reduced channel activity. In these families, heterozygosity for the dominant variants results in less severe disease than biallelic inheritance of two variant alleles. The clinical consequences of variants with partial and complete loss of SCN8A function are variable and likely to be influenced by genetic background.