Anatomically Defined and Functionally Distinct Dorsal Raphe Serotonin Sub-systems.

The dorsal raphe (DR) constitutes a major serotonergic input to the forebrain and modulates diverse functions and brain states, including mood, anxiety, and sensory and motor functions. Most functional studies to date have treated DR serotonin neurons as a single population. Using viral-genetic methods, we found that subcortical- and cortical-projecting serotonin neurons have distinct cell-body distributions within the DR and differentially co-express a vesicular glutamate transporter. Further, amygdala- and frontal-cortex-projecting DR serotonin neurons have largely complementary whole-brain collateralization patterns, receive biased inputs from presynaptic partners, and exhibit opposite responses to aversive stimuli. Gain- and loss-of-function experiments suggest that amygdala-projecting DR serotonin neurons promote anxiety-like behavior, whereas frontal-cortex-projecting neurons promote active coping in the face of challenge. These results provide compelling evidence that the DR serotonin system contains parallel sub-systems that differ in input and output connectivity, physiological response properties, and behavioral functions.

Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia.

How extrinsic stimuli and intrinsic factors interact to regulate continuous neurogenesis in the postnatal mammalian brain is unknown. Here we show that regulation of dendritic development of newborn neurons by Disrupted-in-Schizophrenia 1 (DISC1) during adult hippocampal neurogenesis requires neurotransmitter GABA-induced, NKCC1-dependent depolarization through a convergence onto the AKT-mTOR pathway. In contrast, DISC1 fails to modulate early-postnatal hippocampal neurogenesis when conversion of GABA-induced depolarization to hyperpolarization is accelerated. Extending the period of GABA-induced depolarization or maternal deprivation stress restores DISC1-dependent dendritic regulation through mTOR pathway during early-postnatal hippocampal neurogenesis. Furthermore, DISC1 and NKCC1 interact epistatically to affect risk for schizophrenia in two independent case control studies. Our study uncovers an interplay between intrinsic DISC1 and extrinsic GABA signaling, two schizophrenia susceptibility pathways, in controlling neurogenesis and suggests critical roles of developmental tempo and experience in manifesting the impact of susceptibility genes on neuronal development and risk for mental disorders.

Association of oral microbiome with oral human papillomavirus infection: a population study of the National Health and Nutrition Examination Survey, 2009-2012.

BACKGROUND: Oral human papillomavirus(HPV) infection and the oral microbiome are associated with oropharyngeal cancer. However, population-based data on the association of oral microbiome with oral HPV infection are limited. METHOD: We performed a cross-sectional analysis of 5,496 participants aged 20-59 in National Health and Nutrition Examination Surveys(NHANES):2009-2012. The association between either oral microbiome alpha diversity or beta diversity and oral HPV infection was assessed using multivariable logistic regression or principal coordinate analyses(PCoA) and multivariate analysis of variance(PERMANOVA). RESULTS: For alpha diversity, we found a lower number of observed Amplicon sequence variants(ASVs) (adjusted odds ratio[aOR] = 0.996; 95%CI = 0.992-0.999) and reduced Faith's Phylogenetic Diversity(aOR = 0.95; 95%CI = 0.90-0.99) associated with high-risk oral HPV infection in the overall population. This trend was observed in males for both high-risk and any oral HPV infection. Beta diversity showed differentiation of oral microbiome community by high-risk oral HPV infection as measured by Bray-Curtis dissimilarity (R2 = 0.054%; P = .029) and unweighted UniFrac distance (R2 = 0.046%; P = .045) among the overall population, and associations were driven by males. CONCLUSIONS: Both oral microbiome alpha diversity(within-sample richness and phylogenetic diversity) and beta diversity(heterogeneous dispersion of oral microbiome community) are associated with HPV infection. Longitudinal studies are needed to characterize the role of the microbiome in the natural history of oral HPV infection.

Towards a youth mental health paradigm: a perspective and roadmap.

Most mental disorders have a typical onset between 12 and 25 years of age, highlighting the importance of this period for the pathogenesis, diagnosis, and treatment of mental ill-health. This perspective addresses interactions between risk and protective factors and brain development as key pillars accounting for the emergence of psychopathology in youth. Moreover, we propose that novel approaches towards early diagnosis and interventions are required that reflect the evolution of emerging psychopathology, the importance of novel service models, and knowledge exchange between science and practitioners. Taken together, we propose a transformative early intervention paradigm for research and clinical care that could significantly enhance mental health in young people and initiate a shift towards the prevention of severe mental disorders.

Prenatal mental health and emotional experiences during the pandemic: associations with infant neurodevelopment screening results.

BACKGROUND: This study determined whether parental mental health and emotional experiences during the prenatal period were linked to infant developmental outcomes through the Ages and Stages Questionnaire (ASQ-3) at 8-10 months. METHODS: Participants included 133 individuals who were living in the US and were pregnant or had given birth within 6 months prior to enrollment. Respondents were majority White with high education and income levels. Online surveys were administered from May 2020 to September 2021; follow-up surveys were administered from November 2020 to August 2022. RESULTS: Parent generalized anxiety symptoms were positively associated with infant communication (ß = 0.34, 95% CI [0.15, 1.76], p < 0.05), while parent-fetal bonding was positively associated with infant communication (ß = 0.20, 95% CI [0.05, 0.76], p < 0.05) and personal-social performance (ß = 0.20, 95% CI [0.04, 0.74], p < 0.05). COVID-19-related worry was negatively associated with infant communication (ß = -0.30, 95% CI [-0.75, -0.12], p < 0.05) and fine motor performance (ß = -0.25, 95% CI [-0.66, -0.03], p < 0.05). CONCLUSION: Parent mental health and emotional experiences may contribute to infant developmental outcomes in high risk conditions such as a pandemic. IMPACT STATEMENT: Maternal SARS-CoV-2 infection has been evaluated in relation to child outcomes, however, parent psychosocial experiences should not be overlooked when considering pandemic risks to child development. Specific prenatal mental health and pandemic-related emotional experiences are associated with infant developmental performance, as assessed by the Ages and Stages. Questionnaire (ASQ-3) at 8 to 10 months old. Findings indicate that parental prenatal anxiety and emotional experiences from the pandemic should be assessed when evaluating child developmental delays.

Synthesis of Phenol-Pyridinium Salts Enabled by Tandem Electron Donor-Acceptor Complexation and Iridium Photocatalysis.

Herein, we describe a dual photocatalytic system to synthesize phenol-pyridinium salts using visible light. Utilizing both electron donor-acceptor (EDA) complex and iridium(III) photocatalytic cycles, the C-N cross-coupling of unprotected phenols and pyridines proceeds in the presence of oxygen to furnish pyridinium salts. Photocatalytic generation of phenoxyl radical cations also enabled a nucleophilic aromatic substitution (SNAr) of a fluorophenol with an electron-poor pyridine. Spectroscopic experiments were conducted to probe the mechanism and reaction selectivity. The unique reactivity of these phenol-pyridinium salts were displayed in several derivatization reactions, providing rapid access to a diverse chemical space.

Communication Strategies to Improve Antibiotic Prescribing in Pediatric Urgent Care Centers.

OBJECTIVE: Urgent care (UC) clinicians frequently prescribe inappropriate antibiotics for upper respiratory illnesses. In a national survey, pediatric UC clinicians reported family expectations as a primary driver for prescribing inappropriate antibiotics. Communication strategies effectively reduce unnecessary antibiotics while increasing family satisfaction. We aimed to reduce inappropriate prescribing practices in otitis media with effusion (OME), acute otitis media (AOM), and pharyngitis in pediatric UC clinics by a relative 20% within 6 months using evidence-based communication strategies. METHODS: We recruited participants via e-mails, newsletters, and Webinars from pediatric and UC national societies. We defined antibiotic-prescribing appropriateness based on consensus guidelines. Family advisors and UC pediatricians developed script templates based on an evidence-based strategy. Participants submitted data electronically. We reported data using line graphs and shared deidentified data during monthly Webinars. We used χ 2 tests to evaluate change in appropriateness at the beginning and end of the study period. RESULTS: The 104 participants from 14 institutions submitted 1183 encounters for analysis in the intervention cycles. Using a strict definition of inappropriateness, overall inappropriate antibiotic prescriptions for all diagnoses trended downward from 26.4% to 16.6% ( P = 0.13). Inappropriate prescriptions trended upward in OME from 30.8% to 46.7% ( P = 0.34) with clinicians' increased use of "watch and wait" for this diagnosis. Inappropriate prescribing for AOM and pharyngitis improved from 38.6% to 26.5% ( P = 0.03) and 14.5% to 8.8% ( P = 0.44), respectively. CONCLUSIONS: Using templates to standardize communication with caregivers, a national collaborative decreased inappropriate antibiotic prescriptions for AOM and had downward trend in inappropriate antibiotic prescriptions for pharyngitis. Clinicians increased the inappropriate use of "watch and wait" antibiotics for OME. Future studies should evaluate barriers to the appropriate use of delayed antibiotic prescriptions.

A Quantitative Assessment of Staphylococcus aureus Community Carriage in Yuma, Arizona.

BACKGROUND: Disease control relies on pathogen identification and understanding reservoirs. Staphylococcus aureus infection prevention is based upon decades of research on colonization and infection, but diminishing returns from mitigation efforts suggest significant knowledge gaps. Existing knowledge and mitigation protocols are founded upon culture-based detection, with almost no information about pathogen quantities. METHODS: We used culture and a quantitative polymerase chain reaction assay on samples from 3 body sites to characterize colonization more comprehensively than previous studies by describing both prevalence and pathogen quantity. RESULTS: We show a much higher overall prevalence (65.9%) than previously documented, with higher quantities and prevalence associated with the nares, non-Hispanic males (86.9%), and correlating with colonization in other body sites. These results suggest that research and clinical practices likely misclassify over half of colonized persons, limiting mitigation measures and their impact. CONCLUSIONS: This work begins the process of rebuilding foundational knowledge of S aureus carriage with more accurate and wholistic approaches.

Iron-Mediated C-H Functionalization of Unactivated Alkynes for the Synthesis of Derivatized Dihydropyrrolones: Regioselectivity Under Thermodynamic Control.

Cyclopentadienyliron dicarbonyl-based complexes present opportunities for underexplored disconnections in synthesis. Access to challenging dihydropyrrolone products is achieved by propargylic C-H functionalization of alkynes for the formation of cyclic organoiron species. Excellent regioselectivity for unsymmetrical alkynes is observed in many cases. Notably, regioselectivity under these stoichiometric conditions diverges from those observed previously under catalysis, occurring at the more-substituted terminus of the alkyne, allowing for methine functionalization and the formation of quaternary centers. Divergent demetallation of the intermediate organoiron complexes gives access to chemically diverse products which are amenable to further functionalization.

Strategies for Naming and Addressing Structural Racism in Immigrant Mental Health.

Immigrants account for 13.7% of the US population, and the great majority of these individuals originate from Latin America or Asia. Immigrant communities experience striking inequities in mental health care, particularly lower rates of mental health service use despite significant stressors. Structural barriers are a significant deterrent to obtaining needed care and are often rooted in racist policies and assumptions. Here we review and summarize key pathways by which underlying structural racism contributes to disparities in immigrant mental health, including anti-immigration policies, labor and financial exploitation, and culturally insensitive mental health services. Significant accumulated research evidence regarding these barriers has failed to translate into structural reform and financial investment required to address them, resulting in pronounced costs to both immigrant populations and society at large. We propose specific strategies for addressing relevant structural inequities, including reforming economic and financial policies, community education initiatives, and task-sharing and strengths-based interventions developed in partnership with immigrant communities to promote access to mental health care for populations in dire need of culturally appropriate services. (Am J Public Health. 2023;113(S1): S72-S79. https://doi.org/10.2105/AJPH.2022.307165).

Integrating sample similarities into latent class analysis: a tree-structured shrinkage approach.

This paper is concerned with using multivariate binary observations to estimate the probabilities of unobserved classes with scientific meanings. We focus on the setting where additional information about sample similarities is available and represented by a rooted weighted tree. Every leaf in the given tree contains multiple samples. Shorter distances over the tree between the leaves indicate a priori higher similarity in class probability vectors. We propose a novel data integrative extension to classical latent class models with tree-structured shrinkage. The proposed approach enables (1) borrowing of information across leaves, (2) estimating data-driven leaf groups with distinct vectors of class probabilities, and (3) individual-level probabilistic class assignment given the observed multivariate binary measurements. We derive and implement a scalable posterior inference algorithm in a variational Bayes framework. Extensive simulations show more accurate estimation of class probabilities than alternatives that suboptimally use the additional sample similarity information. A zoonotic infectious disease application is used to illustrate the proposed approach. The paper concludes by a brief discussion on model limitations and extensions.

Plugging the leaks: antibiotic resistance at human-animal interfaces in low-resource settings.

Antibiotic resistance is one of the greatest public health challenges of our time. International efforts to curb resistance have largely focused on drug development and limiting unnecessary antibiotic use. However, in areas where water, sanitation, and hygiene infrastructure is lacking, we propose that bacterial flow between humans and animals can exacerbate the emergence and spread of resistant pathogens. Here, we describe the consequences of poor environmental controls by comparing mobile resistance elements among Escherichia coli recovered from humans and meat in Cambodia, a middle-income country with substantial human-animal connectivity and unregulated antibiotic use. We identified identical mobile resistance elements and a conserved transposon region that were widely dispersed in both humans and animals, a phenomenon rarely observed in high-income settings. Our findings indicate that plugging leaks at human-animal interfaces should be a critical part of addressing antibiotic resistance in low- and especially middle-income countries.

"My Brigham Baby" Application: A Pilot Study Using Technology to Enhance Parent's Experience in the Neonatal Intensive Care Unit.

OBJECTIVE: This study aimed to describe the family psychosocial experience in a level-III neonatal intensive care unit (NICU), and to assess how it evolved after rollout of an educational smartphone application (App) called "My Brigham Baby." STUDY DESIGN: We surveyed 25 NICU parents pre-App rollout (before coronavirus disease 2019 [COVID-19] pandemic) and 25 parents post-App rollout (during pandemic). Collected data included parental self-reported discharge readiness, symptoms of stress and anxiety, and parenting skill confidence. Survey scores were assessed as total or mean scores, and by category of severity. RESULTS: Pre-and post-App parents had comparable demographics, and their infants had similar clinical characteristics during their NICU stay. Discharge readiness differed by group status (p = 0.02) and was characterized by a greater frequency in being "very ready" for discharge among the post-App rollout parent group compared with the pre-App group (56 vs. 20%, p = 0.027), and parenting confidence shifted toward more optimal scores post-App rollout. Parental stress and anxiety symptoms did not significantly differ between groups despite possible stress contagion from the COVID-19 pandemic. CONCLUSION: This pilot study suggests that technology Apps are feasible interventions within NICU settings and may enhance parental experiences related to NICU hospitalization. KEY POINTS: · Parents' experience increased psychological distress during the time their infant is cared for in the NICU, which has downstream consequences for the family unit.. · In our study, surveyed parents reported higher discharge readiness and parenting confidence shifted toward improvement after rollout of a family education and support smartphone application in a level-III NICU.. · This pilot study suggests that technology applications are feasible interventions that might enhance parental experiences during NICU hospitalization..

Psychological risks to mother-infant bonding during the COVID-19 pandemic.

BACKGROUND: The purpose of this study was to examine the association between mental health symptoms, along with psychological experiences and coronavirus disease 2019 (COVID-19) related concerns, and self-reported maternal-infant bonding experiences of postpartum women. METHODS: Using data collected from May 19 to August 17, 2020, this cross-sectional online study assessed 429 women to better understand the impact of the COVID-19 pandemic on women during the postpartum period. Enrolled respondents were asked to participate in a 30-45-min online survey about COVID-19-related experiences, pregnancy, stress, and well-being. RESULTS: Postpartum women's depressive symptoms were related to lower quality maternal-infant bonding, but the anxiety symptoms were not associated with bonding. Maternal self-efficacy, but not social support, was associated with mothers' higher quality of maternal-infant bonding. COVID-19-related grief was significantly associated with lower quality bonding. On the other hand, COVID-19-related health worries were associated with higher quality of maternal-infant bonding. CONCLUSIONS: We describe potential psychological risk factors to maternal-infant bonding among postpartum women during the pandemic period. To best support the medical and psychological well-being of the mothers and infants, enhanced interdisciplinary partnerships among perinatal healthcare professionals involved in primary and/or specialty care is needed. IMPACT: Unique COVID-19-related health and grief concerns exist, with implications for maternal-infant bonding. Depression but not anxiety is associated with lower maternal-infant bonding. Caregiving confidence, but not social support, is associated with higher maternal-infant bonding. It is critical to screen for postpartum depression and COVID-19-related grief during maternal follow-up and pediatric visits. Study findings inform and prioritize pediatric interventions toward enhancing maternal-infant bonding during the COVID-19 era.

How Does Voluntary Medical Male Circumcision Reduce HIV Risk?

PURPOSE OF REVIEW: Voluntary medical male circumcision (VMMC) is a surgical procedure that reduces HIV acquisition risk by almost two-thirds. However, global implementation is lagging, in part due to VMMC hesitancy. A better understanding of the mechanism(s) by which this procedure protects against HIV may increase acceptance of VMMC as an HIV risk reduction approach among health care providers and their clients. RECENT FINDINGS: HIV acquisition in the uncircumcised penis occurs preferentially across the inner foreskin tissues, due to increased susceptibility that is linked to elevated inflammatory cytokine levels in the sub-preputial space and an increased tissue density of HIV-susceptible CD4 + T cells. Inflammation can be caused by sexually transmitted infections, but is more commonly induced by specific anaerobic components of the penile microbiome. Circumcision protects by both directly removing the susceptible tissues of the inner foreskin, and by inducing a less inflammatory residual penile microbiome. VMMC reduces HIV susceptibility by removing susceptible penile tissues, and also through impacts on the penile immune and microbial milieu. Understanding these mechanisms may not only increase VMMC acceptability and reinvigorate global VMMC programs, but may also lead to non-surgical HIV prevention approaches focused on penile immunology and/or microbiota.

Binge drinking and sexual risk behavior among US sexual and gender minority college students.

BACKGROUND AND OBJECTIVES: Binge drinking and sexual risk behaviors have historically been associated with lesbian, gay, bisexual, and transgender (LGBT) adults; however, few studies have described this association among broader sexual and gender minority (SGM) students, who often identify outside of LGBT (e.g., asexual, queer). This study examined the relationship between binge drinking and sexual risk behaviors among SGM versus non-SGM college students. METHODS: A retrospective analysis was conducted with cross-sectional data from the Spring 2017 American College Health Association-National College Health Assessment (ACHA-NCHA) survey among US undergraduates (n = 47,821) across 92 institutions. Binge drinking was measured as more than five drinks consumed the last time the student socialized; sexual risk behavior was measured as the number of sexual partners in the past 12 months. RESULTS: Numerous undergraduates nationally identify as SGM (19.9%), with bisexual (32.7%), other SGM (26.1%), and asexual (25.4%) students comprising the largest subgroups. Prevalent among both SGM (28.1%) and non-SGM (29.6%) students, binge drinking had a significant main effect on the number of sexual partners. A significant interaction effect was observed between SGM identity and binge drinking on the number of sexual partners, such that this association was stronger in SGM versus non-SGM students. This effect remained significant across multiple SGM subgroups. DISCUSSION AND CONCLUSIONS: SGM students are more prevalent and diverse than previously reported. While prevalent overall, binge drinking may be uniquely sexualized among SGM students. SCIENTIFIC SIGNIFICANCE: In the first large-scale study assessing drinking among disaggregated SGM college students, data suggest tailoring alcohol interventions to SGM students, particularly those identifying outside of LGBT.

Preexisting Depression and Daytime Sleepiness in Women and Men.

BACKGROUND: Sleep problems can persist following the treatment of depression and remission of symptoms. The extent to which having a previous history of depression may be associated with current daytime sleepiness is largely unknown. METHODS: Data were obtained from the spring 2017 American College Health Association-National College Health Assessment (ACHA-NCHA) survey (92 institutions) which assessed self-reported health in U.S. college students (n = 41,670). Among the sample, 93.5% were 18-24 year of age, and 69.6% women. Logistic regression estimated the association between reported prior lifetime diagnosis of depression and daytime sleepiness from the past 7 days, while adjusting for depressive symptoms and antidepressant use from the past year. Unadjusted and adjusted logistic regression models stratified by gender were performed. RESULTS: Among those who reported problems with sleepiness, 31.6% women and 19.4% men had a preexisting depression diagnosis. Individuals with preexisting depression were more likely than those without this diagnosis to report sleepiness problems (women: OR = 1.4, CI = 1.3-1.6, p < .001; men: OR = 1.2, CI = 1.0-1.4, p < .01). However, this association differed significantly by gender, with women with a preexisting depression diagnosis having a 13.0% greater likelihood of sleepiness compared to men. CONCLUSIONS: Those with a preexisting depression diagnosis, and specifically women, may be at risk for daytime sleepiness even in the absence of current depressive mood-related symptoms. Given that many individuals are at risk for daytime sleepiness, mental health initiatives, including those on college campuses, should incorporate sleep hygiene within their programming.

Prenatal distress during the COVID-19 pandemic: clinical and research implications.

PURPOSE: The objective of this study was to identify risk and protective factors related to general prenatal distress and COVID-19-specific prenatal distress to inform intervention targets among women pregnant during the COVID-19 pandemic. METHODS: The study relied on data obtained from U.S. pregnant women (N = 701) who participated in the Perinatal Experiences and COVID-19 Effects (PEACE) Study from May 21 to October 3, 2020. The present cross-sectional study examined the potential risk and protective factors associated with different features of prenatal distress among U.S. pregnant women during the COVID-19 pandemic. RESULTS: Approximately two-thirds of expectant mothers indicated being more stressed about going to the hospital because of COVID-19. Generalized anxiety and PTSD were associated with higher levels of general and COVID-19-specific prenatal distress. Depression symptoms were associated with higher general prenatal distress. Higher levels of distress tolerance were associated with lower levels of general prenatal distress (B = - 0.192, p < .001) and COVID-19-specific prenatal distress (B = - 0.089, p < .05). Higher levels of instrumental social support were marginally associated with lower COVID-19-specific prenatal distress (B = - 0.140, p < 0.1). CONCLUSION: Findings draw attention to prenatal distress experiences during the COVID-19 pandemic, including new types of distress arising from the pandemic itself. Women might benefit from the introduction of interventions such as mindfulness-based or relaxation therapy. Coverage of responsibilities and financial assistance is particularly needed during the COVID-19 pandemic. Limitations include a majority White and high socioeconomic sample. These findings provide specificity regarding potential targets for addressing prenatal distress.

Unexpected changes in birth experiences during the COVID-19 pandemic: Implications for maternal mental health.

PURPOSE: This study examined the rates of unexpected birth experiences due to the COVID-19 pandemic and its association with women's postpartum mental health symptoms (depression, generalized anxiety, and PTSD). METHODS: Our cross-sectional analysis included postpartum women (N = 506) who reported on birth plan changes attributed to the COVID-19 pandemic through the PEACE (Perinatal Experiences and COVID-19 Effects) Study, an online survey that took place between May 2020 and May 2021. Covariates included sociodemographic variables, number of days since the pandemic, pre-pregnancy mental health history, and protective factors such as social support, distress tolerance, and resilience. RESULTS: Prevalent COVID-19 pandemic changes in the birth experience included not having support people (e.g., partners and friends) permitted to participate in the baby's delivery (33.5%), reduced access to preferred medications before or after delivery (9.7%), unavailable health care providers for the baby's birth as planned (9.6%), and other changes (13.8%). The reduced access to medications was associated with those reporting higher levels of depressive (ß = .10, p < .01) and PTSD symptoms (ß = .07, p < .05). Separation from their baby for a long period after delivery (ß = .10, p < .05) and other changes (ß = .10, p < .01) were associated with higher levels of PTSD symptoms. CONCLUSION: Unexpected changes to the birth experience due to the COVID-19 pandemic may have small but persistent effects on depressive and PTSD symptoms. Given increased vigilance and its association with subsequent PTSD, acknowledging any fear of viral contagion within the hospital setting but informing women the plans for ensuring safety may be preventive for later mental health symptomatology.