Pathogenic Interleukin-10 Receptor Alpha Variants in Humans - Balancing Natural Selection and Clinical Implications.

Balancing natural selection is a process by which genetic variants arise in populations that are beneficial to heterozygous carriers, but pathogenic when homozygous. We systematically investigated the prevalence, structural, and functional consequences of pathogenic IL10RA variants that are associated with monogenic inflammatory bowel disease. We identify 36 non-synonymous and non-sense variants in the IL10RA gene. Since the majority of these IL10RA variants have not been functionally characterized, we performed a systematic screening of their impact on STAT3 phosphorylation upon IL-10 stimulation. Based on the geographic accumulation of confirmed pathogenic IL10RA variants in East Asia and in Northeast China, the distribution of infectious disorders worldwide, and the functional evidence of IL-10 signaling in the pathogenesis, we identify Schistosoma japonicum infection as plausible selection pressure driving variation in IL10RA. Consistent with this is a partially augmented IL-10 response in peripheral blood mononuclear cells from heterozygous variant carriers. A parasite-driven heterozygote advantage through reduced IL-10 signaling has implications for health care utilization in regions with high allele frequencies and potentially indicates pathogen eradication strategies that target IL-10 signaling.

Religiosity and Young Unmarried Women's Sexual and Contraceptive Behavior: New Evidence From a Longitudinal Panel of Young Adult Women.

Drawing on weekly panel data from the Relationship Dynamics and Social Life study, we investigate the relationship between religiosity and young Christian women's premarital intercourse, hormonal contraceptive use, and condom use for a period of up to 2.5 years. Mediation analyses reveal what explains the relationship between baseline religiosity and young women's subsequent reproductive behaviors, with consideration for their normative environments, moral order and learned competencies, attitudes, and anticipated guilt after sex. Results indicate that the more religious a young woman is, the less likely she is to have intercourse and to use hormonal contraception in a given week. However, when having intercourse and not using a hormonal method, the more religious a young woman is, the more likely she is to use condoms. Religiosity's relationship to these behaviors operates largely through women's reproductive attitudes, anticipated feelings of guilt after sex, and past sexual or contraceptive behaviors. Together, these findings highlight the complex relationship between religiosity and premarital sex and contraceptive use, elucidate key pathways through which religiosity operates, and draw attention to the often overlooked role of sexual emotions.

International Migration and Modern Contraceptive Use: A Research Note on African Migrants to France.

This research note presents a multisited analysis of migration and contraceptive use by standardizing and integrating a sample of African migrants in France from six West and Central African countries in the Trajectoires et Origines survey with a sample of women living in the same six African countries in the Demographic and Health Surveys. Descriptive analyses indicate that the contraceptive use of migrants more closely aligns with that of native French women than with that of women from origin countries. In particular, migrants report dramatically higher use of long-acting reversible contraceptives and short-acting hormonal methods and lower use of traditional methods than do women in the countries of origin. Although migrants differ from women in the countries of origin on observed characteristics, including education and family background, reweighting women in the origin countries to resemble migrants on these characteristics does little to explain differences in contraceptive use between the groups. Given that contraceptive use is an important proximate determinant of fertility, our results suggest that contraceptive use should feature more prominently in the dominant demographic paradigms of migrant fertility.

Medication abortion use among low-income and rural Texans before and during state-imposed restrictions and after FDA-updated labeling.

BACKGROUND: In 2013, the Texas legislature passed House Bill 2, restricting use of medication abortion to comply with Food and Drug Administration labeling from 2000. The Food and Drug Administration updated its labeling for medication abortion in 2016, alleviating some of the burdens imposed by House Bill 2. OBJECTIVE: Our objective was to identify the impact of House Bill 2 on medication abortion use by patient travel distance to an open clinic and income status. MATERIALS AND METHODS: In this retrospective study, we collected patient zip code, county of residence, type of abortion, family size, and income data on all patients who received an abortion (medication or aspiration) from 7 Texas abortion clinics in 3 time periods: pre-House Bill 2 (July 1, 2012-June 30, 2013), during House Bill 2 (April 1, 2015-March 30, 2016), and post-Food and Drug Administration labeling update (April 1, 2016-March 30, 2017). Patient driving distance to the clinic where care was obtained was categorized as 1-24, 25-49, 50-99, or 100+ miles. Patient county of residence was categorized by availability of a clinic during House Bill 2 (open clinic), county with a House Bill 2-related clinic closure (closed clinic), or no clinic any time period. Patient income was categorized as ≤110% federal poverty level (low-income) and >110% federal poverty level. Change in medication abortion use in the 3 time periods by patient driving distance, residence in a county with an open clinic, and income status were evaluated using χ2 tests and logistic regression. We used geospatial mapping to depict the spatial distribution of patients who obtained a medication abortion in each time period. RESULTS: Among 70,578 abortion procedures, medication abortion comprised 26%, 7%, and 29% of cases pre-House Bill 2, during House Bill 2, and post-Food and Drug Administration labeling update, respectively. During House Bill 2, patients traveling 100+ miles compared to 1- 24 miles were less likely to use medication abortion (odds ratio, 0.21; 95% confidence interval, 0.15, 0.30), as were low-income compared to higher-income patients (odds ratio, 0.76; 95% confidence interval, 0.68, 0.85), and low-income, distant patients (adjusted odds ratio, 0.14; 95% confidence interval, 0.08, 0.25). Similarly, post-Food and Drug Administration labeling update, rebound in medication abortion use was less pronounced for patients traveling 100+ miles compared to 1-24 miles (odds ratio, 0.82; 95% confidence interval, 0.74, 0.91), low-income compared to higher-income patients (odds ratio, 0.77; 95% confidence interval, 0.72, 0.81), and low-income, distant patients (adjusted odds ratio, 0.80; 95% confidence interval, 0.68, 0.94). Post-Food and Drug Administration labeling update, patients residing in counties with House Bill 2-related clinic closures were less likely to receive medication abortion as driving distance increased (52% traveling 25-49 miles, 41% traveling 50-99 miles, and 26% traveling 100+ miles, P < .05). Geospatial mapping demonstrated that patients traveled from all over the state to receive medication abortion pre-House Bill 2 and post-Food and Drug Administration labeling update, whereas during House Bill 2, only those living in or near a county with an open clinic obtained medication abortion. CONCLUSION: Texas state law drastically restricted access to medication abortion and had a disproportionate impact on low-income patients and those living farther from an open clinic. After the Food and Drug Administration labeling update, medication abortion use rebounded, but disparities in use remained.

Spore-forming Bacillus coagulans SNZ 1969 improved intestinal motility and constipation perception mediated by microbial alterations in healthy adults with mild intermittent constipation: A randomized controlled trial.

The spore-forming Bacillus coagulans has attracted attention for their therapeutic action in the colon. However, the mechanism of this action remains unclear. In this study, healthy subjects with mild intermittent constipation were supplemented with B. coagulans SNZ 1969 (BC) or the placebo for 8 weeks (n = 80). Then, we assessed colonic transit time (CTT), weekly complete spontaneous bowel movement (CSBM) scores, bowel discomfort symptom (BDS) scores, and 16S rRNA fecal microbiome profiles. The association between the critically altered gut microbiome and clinical outcomes was analyzed using redundancy analysis (RDA) and validated by receiver operating characteristic (ROC) curves. BC supplementation significantly improved CTT (p = 0.031), CSBM at weeks 2 (p = 0.045) and 9 (p = 0.038), and BDS at weeks 3 (p = 0.019) and 6 (p = 0.029) compared with the placebo, while altering the community composition of the gut microbiota. We also confirmed that BC was effectively delivered to the gut. Finally, the multivariate redundancy analysis concluded that BC-induced enrichment of Lactobacillales and diminishment of Synergistales were related to CTT improvements. This study provides important new data on how spore-forming B. coagulans SNZ 1969 contributes to improving gut motility and presents evidence supporting the use of B. coagulans SNZ 1969 in adults with mild intermittent constipation and habitual low intake of fruit and vegetables.

Differences in abortion rates by race-ethnicity after implementation of a restrictive Texas law.

OBJECTIVE: To evaluate the association between a restrictive Texas law, House Bill 2 (HB2), and receipt of in-clinic abortion by patient's race-ethnicity. STUDY DESIGN: In this retrospective cohort study, we collected Texas state statistics on number of abortions, abortions per county, and abortions per county by race-ethnicity for 2012, before HB2 was enacted, and 2015, after HB2 was in effect. Using female reproductive-aged population estimates, we calculated the abortion rate and percent change in the abortion rate between the two time periods by county, patient residence in a county with an open clinic or HB2-related clinic closure, and change in distance to an open clinic for each race-ethnicity. We also used geospatial analyses to depict the greatest decrease in abortion rate by race-ethnicity and county. RESULTS: In Texas, there were 64,716 reported abortions in 2012 and 54,253 in 2015. Statewide, there was a 20% decrease in the abortion rate affecting all racial-ethnic groups, yet the reduction was greater among Hispanic women compared to White women (-25% vs. -16%, respectively). The abortion rate also decreased more among those living in a county with an HB2-related clinic closure, especially for Hispanic women (-41% Hispanic vs. -29% White vs. -30% Black vs. -3% Other). Hispanic women whose travel distance increased 100+ miles had the greatest reduction in the abortion rate (-43%). Geospatial mapping confirmed our quantitative findings. CONCLUSION: HB2 led to a disproportionate reduction in the abortion rate among Hispanic women in Texas, including those living in counties with a closed clinic or traveling long distances to obtain in-clinic abortion care. IMPLICATIONS: Restrictive abortion policies in Texas may disproportionately burden Hispanic women and those affected by clinic closures.