Affective symptoms in pregnancy are associated with the vaginal microbiome.

BACKGROUND: Composition of the vaginal microbiome in pregnancy is associated with adverse maternal, obstetric, and child health outcomes. Therefore, identifying sources of individual differences in the vaginal microbiome is of considerable clinical and public health interest. The current study tested the hypothesis that vaginal microbiome composition during pregnancy is associated with an individual's experience of affective symptoms and stress exposure. METHODS: Data were based on a prospective longitudinal study of a medically healthy community sample of 275 mother-infant pairs. Affective symptoms and stress exposure and select measures of associated biomarkers (diurnal salivary cortisol, serum measures of sex hormones) were collected at each trimester; self-report, clinical, and medical records were used to collect detailed data on socio-demographic factors and health behavior, including diet and sleep. Vaginal microbiome samples were collected in the third trimester (34-40 weeks) and characterized by 16S rRNA sequencing. Identified taxa were clustered into three community clusters (CC1-3) based on dissimilarity of vaginal microbiota composition. RESULTS: Results indicate that depressive symptoms during pregnancy were reliably associated with individual taxa and CC3 in the third trimester. Prediction of functional potential from 16S taxonomy revealed a differential abundance of metabolic pathways in CC1-3 and individual taxa, including biosynthetic pathways for serotonin and dopamine. We did not find robust evidence linking symptom- and stress-related biomarkers and CCs. CONCLUSIONS: Our results provide further evidence of how prenatal psychological distress during pregnancy alters the maternal-fetal microbiome ecosystem that may be important for understanding maternal and child health outcomes.

Affective Symptoms in Pregnancy are Associated with the Vaginal Microbiome.

Composition of the vaginal microbiome in pregnancy is associated with adverse maternal, obstetric, and child health outcomes. Identifying the sources of individual differences in the vaginal microbiome is therefore of considerable clinical and public health interest. The current study tested the hypothesis that vaginal microbiome composition during pregnancy is associated with an individual's experience of affective symptoms and stress exposure. Data were based on a prospective longitudinal study of a diverse and medically healthy community sample of 275 mother-infant pairs. Affective symptoms and stress exposure and select measures of associated biomarkers (diurnal salivary cortisol, serum measures of sex hormones) were collected at each trimester; self-report, clinical, and medical records were used to collect detailed data on socio-demographic factors and health behavior, including diet and sleep. Vaginal microbiome samples were collected in the third trimester (34-40 weeks) and characterized by 16S rRNA sequencing. Identified taxa were clustered into three community state types (CST1-3) based on dissimilarity of vaginal microbiota composition. Results indicate that depressive symptoms during pregnancy were reliably associated with individual taxa and CST3 in the third trimester. Prediction of functional potential from 16S taxonomy revealed a differential abundance of metabolic pathways in CST1-3 and individual taxa, including biosynthetic pathways for the neuroactive metabolites, serotonin and dopamine. With the exception of bioavailable testosterone, no significant associations were found between symptoms- and stress-related biomarkers and CSTs. Our results provide further evidence of how prenatal psychological distress during pregnancy alters the maternal-fetal microbiome ecosystem that may be important for understanding maternal and child health outcomes.

De Novo Design of κ-Opioid Receptor Antagonists Using a Generative Deep Learning Framework.

Likely effective pharmacological interventions for the treatment of opioid addiction include attempts to attenuate brain reward deficits during periods of abstinence. Pharmacological blockade of the κ-opioid receptor (KOR) has been shown to abolish brain reward deficits in rodents during withdrawal, as well as to reduce the escalation of opioid use in rats with extended access to opioids. Although KOR antagonists represent promising candidates for the treatment of opioid addiction, very few potent selective KOR antagonists are known to date and most of them exhibit significant safety concerns. Here, we used a generative deep learning framework for the de novo design of chemotypes with putative KOR antagonistic activity. Molecules generated by models trained with this framework were prioritized for chemical synthesis based on their predicted optimal interactions with the receptor. Our models and proposed training protocol were experimentally validated by binding and functional assays.

Publication Rate of Podium Presentations From the North American Spine Society Annual Meetings.

STUDY DESIGN: Observational study. OBJECTIVES: To determine the publication rate of podium presentations from the North American Spine Society (NASS) annual meetings from the years 2009 to 2011. METHODS: In April 2015, a PubMed search was conducted using titles from the paper presentations as well as the authors. Of the search results that were found, the specific scientific journal in which the article was published was recorded. We analyzed further the top 4 destination journals and trends in publications in these journals over the study period. No study funding was obtained for this research, and there are no potential conflicts of interest or associated biases. RESULTS: Over the study period, 671 paper presentations were available and 342 were published (51% publication rate). The highest publication rate was from the 2011 annual meeting, with 55.3%, and the lowest year was 2010, with a rate of 46.43%. Spine (32.75%), The Spine Journal (19.01%), Journal of Neurosurgery Spine (7.31%), and European Spine Journal (6.73%) were the top 4 destination journals. Over the study period, we found a significant decrease in publication rate in Spine (P = .001) and a significant increase in publication rate in The Spine Journal (P = .003). There were no significant difference in publication rate over the study period in Journal of Neurosurgery Spine (P = .15) or European Spine Journal (P = .23). CONCLUSIONS: This is the first study to our knowledge evaluating the publication rate of podium presentations from recent North American Spine Society annual meetings. We found an overall publication rate of 51%.

A population-based analysis of emergent vs. elective hospital admissions for an intrathoracic stomach.

BACKGROUND: Large-scale, population-based analyses of the demographics, management, and healthcare resource utilization of patients with an intrathoracic stomach are largely unknown, an issue which has become more important with the aging of the population. Our objective was to understand the magnitude of the problem and to assess clinical outcomes and hospital costs in elective and emergent admissions of patients with an intrathoracic stomach in a large population-based study. METHODS: The New York Statewide Planning and Research Cooperative System (SPARCS) administrative database was queried for primary ICD-9-CM codes 553.3 and 552.3 in patients 18 years or older; 4858 hospital admissions were identified over a 5-year period (2002-2006). Database variables included age, gender, race, type of admission, operative intervention, in-hospital mortality, length of stay, and cost. RESULTS: Approximately 1000 patients are admitted to the hospital each year with primary diagnosis of intrathoracic stomach, an estimated 52 per 1 million of the population in New York State. Over half of those (53%) were emergent admissions. Interestingly, the majority of emergent admissions (66%) were discharged before any surgical intervention. Patients admitted emergently were older (68.0 vs. 62.1 years, p < 0.0001) and more likely African-American (12% vs. 6%, p < 0.0001). Compared to elective admissions, emergent admissions had higher mortality (2.7% vs. 1.2%, p < 0.001), longer length of stay (LOS) (7.3 vs. 4.9 days, p < 0.0001), and higher cost ($28,484 vs. $24,069, p < 0.001). Among patients who underwent surgery, emergent admissions had higher mortality (5.1% vs. 1.1%, p < 0.0001), greater LOS (13.1 vs. 4.9 days, p < 0.0001), and higher costs ($55,460 vs. $24,760, p < 0.0001). Multivariate regression analysis demonstrated age, emergent presentation, and operative admission as independent predictors for hospital mortality, LOS, and cost (p < 0.0001). CONCLUSIONS: Strikingly, more than half of admissions for intrathoracic stomach were emergent. Emergent admissions had higher mortality, longer LOS, and higher cost than elective admissions. These data support consideration of early elective repair.