School of Medicine: Recent submissions
Now showing items 1-20 of 2750
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Socioeconomic and microenvironmental factors associated with the vaginal microbiota throughout the adult lifespanApproximately 84% of menopausal women experience symptoms and signs of the genitourinary syndrome of menopause (GSM), including vaginal dryness and vulvovaginal atrophy. During peri- and postmenopause, decreased estrogen is often accompanied by alterations of the vaginal microbiota and a perturbed local immune environment. While the vaginal microbiota is known to be dynamic in premenopause, temporal dynamics are understudied in menopause, and shifts toward profiles deficient in protective Lactobacillus spp. (with higher abundance of other anerobic and aerobic bacteria) may increase risk of gynecologic infections and GSM. Immune biomarkers have not been assessed with GSM while considering the composition of the vaginal microbiota. Socioeconomic status (SES), race, and ethnicity also impact the vaginal microbiota. While a single variable for race is often included in microbiome studies, few have evaluated contextual socioeconomic mechanisms. In this dissertation, Aim 1 compared the vaginal microbial longitudinal dynamics (characterized by 16S rRNA gene sequencing of mid-vaginal samples collected twice weekly) of pre-, peri-, and postmenopausal participants in an 8-week cohort. Bacterial community stability, as measured by longitudinal clustering of vaginal community state types (CSTs), Yue-Clayton similarity indices, and other metrics, was comparable by reproductive stage. Aim 2 involved a case-control study of GSM cases and age- and CST-matched controls. Cervical specimens were used to quantify concentrations of 70 immune markers. A proinflammatory state, defined as having at least three of seven predetermined analytes (IL-1β, IL-8, IL-23, MIP-1α, MIP-1β, IP-10, and RANTES) in the upper quartile, was associated with higher odds of GSM. A network analysis also revealed a cluster with proinflammatory IL-17F and IL-31 as its hubs in association with GSM. Aim 3 examined how the vaginal microbiota of participants enrolled in a cohort study differed by a composite score of individual- and neighborhood-level SES factors. Participants classified in the lowest SES score tertile displayed higher odds of a profile characterized by low Lactobacillus spp. abundance compared to those in the upper tertiles, even after adjustment for race and ethnicity. These findings contribute to the understanding of compositional differences in the vaginal microenvironment of diverse women and identify molecular targets for treatment and/or prevention of GSM.
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Long noncoding RNA uc. 173 enhances intestinal epithelial renewal by increasing function of Paneth cell/stem cell niche via mitochondriaLong ncRNA uc.173 has recently been indicated as a promotor of regeneration of the intestinal mucosa. The epithelium of the intestinal mucosa is a rapidly self-renewing tissue in the body, but the renewal process is often defective due to various diseases. However, the exact underlying mechanism remains unknown. Here, we investigated the role of the PC/ISC niche in uc.173-reguated intestinal mucosal growth and further investigated mitochondrial metabolism in this process
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Proteome Remodeling in a Peptide Immunization Animal Model of Anti-NMDAR EncephalitisAnti-NMDAR encephalitis is the most common subtype of autoimmune encephalitis (AIE) and is characterized by GluN1 antibodies. Disease is associated with substantial morbidity and mortality, highlighting critical unmet therapeutic needs. Most animal models of anti-NMDAR encephalitis depend on intracerebroventricular transfer of patient-derived antibodies or cerebrospinal fluid (CSF), or immunization with structurally intact NMDARs. However, recent studies have demonstrated the induction of anti-NMDAR encephalitis in rodent models through GluN1 peptide immunization, with differing effects. Anti-NMDAR antibodies target the amino terminal domain of the GluN1 subunit, and cause receptor loss and associated neuropsychiatric symptoms such as memory impairment, psychosis, and seizures with high morbidity and mortality. The immunopathogenesis remains unclear and therapeutic management of anti-NMDAR encephalitis have been limited by incomplete knowledge of its pathogenesis.
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The Neglect of Children: Food for Thought and ActionThis commentary highlights several challenges concerning the conceptualization of child neglect and the approach to this prevalent problem, with the goal of stimulating further thought and hopefully action. Examples include consideration of potential harm, the role of culture, intentionality, and new forms of neglect related to new knowledge of children’s needs. Assessment of possible neglect, interviewing children, use of motivational interviewing, and the importance of identifying families’ strengths are additional issues. Finally, the commentary addresses alternative response systems, resilience, prevention, and advocacy. We suggest ways to tackle these challenges.
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Kinship Care: Suggestions for Future ResearchControversial issues concerning kinship care are presented, followed by a brief presentation of findings from a survey of child welfare experts on their research priorities for kinship care. These suggestions for future research, as well as those of the author, are discussed in the following categories: children, families, services, state policies, experience of professionals and families, practice issues, and training.
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Protocol for comparing two training approaches for primary care professionals implementing the Safe Environment for Every Kid (SEEK) modelChild maltreatment (CM) is a major public health problem, affecting many lives, in the short and long term, and costing individuals, families, and society dearly. There is a need for broad implementation of evidence-based preventive interventions, such as the Safe Environment for Every Kid (SEEK) model, developed for pediatric primary care. Primary care offers an excellent opportunity to help address prevalent psychosocial problems (e.g., parental depression) that are risk factors for CM. By addressing such problems, SEEK can strengthen families and support parents; promote children’s health, development, and safety; help prevent CM; and benefit the health of the US population. This study will examine intervention strategies for optimizing SEEK’s adoption, implementation, and sustainment, and its effectiveness in preventing CM. Despite strong evidence from two federally funded randomized controlled trials, SEEK has not been widely adopted. The goal of this study is to examine technology-driven implementation strategies to scale-up SEEK—in pediatric and family medicine primary care settings. The aims are to (1) evaluate the effectiveness of training strategies on SEEK’s implementation in primary care practices, (2) evaluate barriers and facilitators to successful implementation and sustainment of SEEK, and (3) examine the model’s effectiveness in preventing CM and the economic costs of implementing SEEK.
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Childhood neglect: The role of the paediatricianNeglect is a pervasive form of child maltreatment. Health care practitioners often struggle with deciding when an action (or lack of action) by a caregiver constitutes inadequate care and is neglectful. The present article discusses the epidemiology, risk factors and outcomes of neglect. In addition, assessment using objective markers, such as harm and potential harm, in the identification of neglect is described, and unique factors that impact assessing and addressing issues of neglect in the clinical setting are discussed. Practical strategies for intervening in cases of neglect are discussed, including how to engage families in which there are concerns for neglect, mandated reporting, working collaboratively with children’s services, ongoing monitoring of families, and how health care professionals can effectively engage in neglect prevention and advocacy.
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Child Sexual Abuse Evaluations: Adherence to RecommendationsSixty-eight parents of children with alleged child sexual abuse (CSA) were surveyed 4 months after visiting an interdisciplinary CSA evaluation clinic in order to examine the extent to which recommendations were recalled and implemented. Of those parents for whom specific recommendations were provided, 9% recalled recommendations for medical follow-up, 79% recalled recommendations for child therapy, and 43% recalled recommendations for parental therapy. Families were more likely to receive and adhere to recommendations when there were behavioral problems and a strong indication of CSA. To improve communication with families, the reasons for recommendations must be clearly conveyed, and possible barriers to implementation should be anticipated and addressed. In addition, recommendations need to be realistic, and professionals need to facilitate the implementation of their treatment plan.
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Health Care Needs of Children in the Foster Care SystemNearly 750 000 children are currently in foster care in the United States. Recent trends in foster care include reliance on extended family members to care for children in kinship care placements, increased efforts to reduce the length of placement, acceleration of termination of parental rights proceedings, and emphasis on adoption. It is not clear what impact welfare reform may have on the number of children who may require foster care placement. Although most children enter foster care with medical, mental health, or developmental problems, many do not receive adequate or appropriate care while in placement. Psychological and emotional problems, in particular, may worsen rather than improve. Multiple barriers to adequate health care for this population exist. Health care practitioners can help to improve the health and well-being of children in foster care by performing timely and thorough admission evaluations, providing continuity of care, and playing an active advocacy role. Potential areas for health services research include study of the impact of different models of health care delivery, the role of a medical home in providing continuity of care, the perception of the foster care experience by the child, children's adjustment to foster care, and foster parent education on health outcomes. Pediatrics 2000;106:909±918; foster care, child welfare, children with special health care needs.
