Comparison of different definitions of traumatic brain injury: implications for cohort characteristics and survival in women, Philadelphia, USA.

BACKGROUND: Traumatic brain injury (TBI) is an acute injury that is understudied in civilian cohorts, especially among women, as TBI has historically been considered to be largely a condition of athletes and military service people. Both the Centres for Disease Control and Prevention (CDC) and Department of Defense (DOD)/Veterans Affairs (VA) have developed case definitions to identify patients with TBI from medical records; however, their definitions differ. We sought to re-examine these definitions to construct an expansive and more inclusive definition among a cohort of women with TBI. METHODS: In this study, we use electronic health records (EHR) from a single healthcare system to study the impact of using different case definitions to identify patients with TBI. Specifically, we identified adult female patients with TBI using the CDC definition, DOD/VA definition and a combined and expanded definition herein called the Penn definition. RESULTS: We identified 4446 adult-female TBI patients meeting the CDC definition, 3619 meeting the DOD/VA definition, and together, 6432 meeting our expanded Penn definition that includes the CDC ad DOD/VA definitions. CONCLUSIONS: Using the expanded definition identified almost two times as many patients, enabling investigations to more fully characterise these patients and related outcomes. Our expanded TBI case definition is available to other researchers interested in employing EHRs to investigate TBI.

State-of-the-Science of human papillomavirus vaccination in women with human immunodeficiency Virus: Summary of a scientific workshop.

The burden of cervical cancer is disproportionately distributed globally, with the vast majority of cases occurring in low- and middle-income countries. Women with human immunodeficiency virus (HIV) (WWH) are at increased risk of human papillomavirus (HPV) infection and cervical cancer as compared to HIV-negative individuals. HPV vaccination remains a priority in regions with a high burden of cervical cancer and high HIV prevalence. With HPV vaccines becoming more accessible, optimal use beyond the initial World Health Organization-recommended target population of 9 to 14-year-old girls is an important question. In March 2022, a group of experts in epidemiology, immunology, and vaccinology convened to discuss the state-of-the-science of HPV vaccination in WWH. This report summarizes the proceedings: review of HIV epidemiology and its intersection with cervical cancer burden, immunology, HPV vaccination including reduced-dose schedules and experience with other vaccines in people with HIV (PWH), HPV vaccination strategies and knowledge gaps, and outstanding research questions. Studies of HPV vaccine effectiveness among WWH, including duration of protection, are limited. Until data from ongoing research is available, the current recommendation for WWH remains for a multi-dose HPV vaccination regimen. A focus of the discussion included the potential impact of HIV acquisition following HPV vaccination. With no data currently existing for HPV vaccines and limited information from non-HPV vaccines, this question requires further research. Implementation research on optimal HPV vaccine delivery approaches for WWH and other priority populations is also urgently needed.

Design and Evaluation of a Postpartum Depression Ontology.

OBJECTIVE: Postpartum depression (PPD) remains an understudied research area despite its high prevalence. The goal of this study is to develop an ontology to aid in the identification of patients with PPD and to enable future analyses with electronic health record (EHR) data. METHODS: We used Protégé-OWL to construct a postpartum depression ontology (PDO) of relevant comorbidities, symptoms, treatments, and other items pertinent to the study and treatment of PPD. RESULTS: The PDO identifies and visualizes the risk factor status of variables for PPD, including comorbidities, confounders, symptoms, and treatments. The PDO includes 734 classes, 13 object properties, and 4,844 individuals. We also linked known and potential risk factors to their respective codes in the International Classification of Diseases versions 9 and 10 that would be useful in structured EHR data analyses. The representation and usefulness of the PDO was assessed using a task-based patient case study approach, involving 10 PPD case studies. Final evaluation of the ontology yielded 86.4% coverage of PPD symptoms, treatments, and risk factors. This demonstrates strong coverage of the PDO for the PPD domain. CONCLUSION: The PDO will enable future researchers to study PPD using EHR data as it contains important information with regard to structured (e.g., billing codes) and unstructured data (e.g., synonyms of symptoms not coded in EHRs). The PDO is publicly available through the National Center for Biomedical Ontology (NCBO) BioPortal ( https://bioportal.bioontology.org/ontologies/PARTUMDO ) which will enable other informaticists to utilize the PDO to study PPD in other populations.

Rural Perinatal Loss: A Needs Assessment.

The purpose of this research was to ascertain the availability and depth of services of bereavement care for mothers who live rurally. The specific focus is on those who experienced early losses including pregnancy, stillbirth, neonatal, and young children who were born with fetal anomalies or neonatal disease that resulted in death. The convenience (nonprobability) sample originated from a population of mothers who lived in rural east central Minnesota. Participants were interviewed in a 60-minute interval. All data were coded confidential. Common themes, incidence of resources, or lack of bereavement resources for the participants' lived experiences were considered using a descriptive phenomenological approach. Our appreciation of the continuing bond between mother and child compels us to believe that there is an ethical obligation to reduce and remove these barriers and inequalities in bereavement support services for those who live rurally and have experienced perinatal and infant loss. Results of this study indicate the need for further study and establishment of bereavement resources in rural outreach for perinatal and early childhood loss.

Single cell analysis of autism patient with bi-allelic NRXN1-alpha deletion reveals skewed fate choice in neural progenitors and impaired neuronal functionality.

We generated human iPS derived neural stem cells and differentiated cells from healthy control individuals and an individual with autism spectrum disorder carrying bi-allelic NRXN1-alpha deletion. We investigated the expression of NRXN1-alpha during neural induction and neural differentiation and observed a pivotal role for NRXN1-alpha during early neural induction and neuronal differentiation. Single cell RNA-seq pinpointed neural stem cells carrying NRXN1-alpha deletion shifting towards radial glia-like cell identity and revealed higher proportion of differentiated astroglia. Furthermore, neuronal cells carrying NRXN1-alpha deletion were identified as immature by single cell RNA-seq analysis, displayed significant depression in calcium signaling activity and presented impaired maturation action potential profile in neurons investigated with electrophysiology. Our observations propose NRXN1-alpha plays an important role for the efficient establishment of neural stem cells, in neuronal differentiation and in maturation of functional excitatory neuronal cells.

Twenty-four-hour motor activity and body temperature patterns suggest altered central circadian timekeeping in Smith-Magenis syndrome, a neurodevelopmental disorder.

Smith-Magenis syndrome (SMS) is a contiguous gene syndrome linked to interstitial microdeletion, or mutation of RAI1, within chromosome 17p11.2. Key behavioral features of SMS include intellectual disability, sleep-disturbances, maladaptive, aggressive and self-injurious behaviors, hyperactivity, and sudden changes in mood. A distinguishing feature of this syndrome is an inverted pattern of melatonin characterized by elevated daytime and low nighttime melatonin levels. As the central circadian clock controls the 24-hr rhythm of melatonin, we hypothesized that the clock itself may contribute to the disrupted pattern of melatonin and sleep. In this report, 24-hr patterns of body temperature, a surrogate marker of clock-timing, and continuous wrist activity were collected to examine the links between body temperature, sleep behavior, and the circadian clock. In addition, age-dependent changes in sleep behavior were explored. Actigraphy-estimated sleep time for SMS was 1 hr less than expected across all ages studied. The timing of the 24-hr body temperature (Tb-24) rhythm was phase advanced, but not inverted. Compared to sibling (SIB) controls, the SMS group had less total night sleep, lower sleep efficiency, earlier sleep onset, earlier final awake times, increased waking after sleep onset (WASO), and increased daytime nap duration. The timing of wake onset varied with age, providing evidence of ongoing developmental sleep changes from childhood through adolescence. Clarification of the circadian and developmental factors that contribute to the disrupted and variable sleep patterns in this syndrome will be helpful in identifying more effective individualized treatments.

Autism spectrum features in Smith-Magenis syndrome.

Smith-Magenis syndrome (SMS; OMIM 182290) is a neurodevelopmental disorder characterized by a well-defined pattern of anomalies. The majority of cases are due to a common deletion in chromosome 17p11.2 that includes the RAI1 gene. In children with SMS, autistic-like behaviors and symptoms start to emerge around 18 months of age. This study included 26 individuals (15 females and 11 males), with a confirmed deletion (del 17p11.2). Parents/caregivers were asked to complete the Social Responsiveness Scale (SRS) and the Social Communication Questionnaire (SCQ) both current and lifetime versions. The results suggest that 90% of the sample had SRS scores consistent with autism spectrum disorders. Moreover, females showed more impairment in total T-scores (P = 0.02), in the social cognition (P = 0.01) and autistic mannerisms (P = 0.002) subscales. The SCQ scores are consistent to show that a majority of individuals may meet criteria for autism spectrum disorders at some point in their lifetime. These results suggest that SMS needs to be considered in the differential diagnosis of autism spectrum disorders but also that therapeutic interventions for autism are likely to benefit individuals with SMS. The mechanisms by which the deletion of RAI1 and contiguous genes cause psychopathology remain unknown but they provide a solid starting point for further studies of gene-brain-behavior interactions in SMS and autism spectrum disorders.

Pharmacological treatment of disruptive behavior in Smith-Magenis syndrome.

Smith-Magenis syndrome (SMS) is a complex genetic syndrome caused by an interstitial deletion of chromosome 17p11.2. Children and adults with SMS appear to have unique neurobehavioral problems that include: sleep disturbance, self-injurious and maladaptive behaviors, stereotypies, and sensory integration disorders. We gathered retrospective psychotropic use information from parents or other caregivers of 62 individuals with SMS who were asked about use of psychotropic medication from a list of commonly used psychiatric medications. For those drugs identified, respondents were asked to rate the experience with the particular medication using a likert-type scale. Drugs were grouped into seven main categories: (1) stimulants; (2) antidepressants; (3) antipsychotics; (4) sleep aides; (5) mood stabilizers; (6) alpha 2 agonists; and (7) benzodiazepines. Relative frequencies, means and standard deviations pertaining to age and medication effect were derived for each medication category. Six of the seven medication categories examined showed no meaningful deviations from the "no change" score. The benzodiazepine group showed a mild detrimental effect. There were no gender differences in efficacy. Use of psychotropic medication started early in life (mean age 5 years), particularly with sleep aides. Although no medication category was identified as efficacious in SMS, all the categories reported herein may be considered as an option for brief symptomatic relief.