Population-Level Correlates of Preterm Delivery among Black and White Women in the U.S

Objective

This study examined the ability of social, demographic, environmental and health-related factors to explain geographic variability in preterm delivery among black and white women in the US and whether these factors explain black-white disparities in preterm delivery.

Methods

We examined county-level prevalence of preterm delivery (20–31 or 32–36 weeks gestation) among singletons born 1998–2002. We conducted multivariable linear regression analysis to estimate the association of selected variables with preterm delivery separately for each preterm/race-ethnicity group.

Results

The prevalence of preterm delivery varied two- to three-fold across U.S. counties, and the distributions were strikingly distinct for blacks and whites. Among births to blacks, regression models explained 46% of the variability in county-level risk of delivery at 20–31 weeks and 55% for delivery at 32–36 weeks (based on R-squared values). Respective percentages for whites were 67% and 71%. Models included socio-environmental/demographic and health-related variables and explained similar amounts of variability overall.

Conclusions

Much of the geographic variability in preterm delivery in the US can be explained by socioeconomic, demographic and health-related characteristics of the population, but less so for blacks than whites.     

A Pre- and Co-Knockdown of RNAseT Enzyme,Eri-1, Enhances the Efficiency of RNAi Induced Gene Silencing in Caenorhabditis elegans

Background

The approach of RNAi mediated gene knockdown, employing exogenous dsRNA, is being beneficially exploited in various fields of functional genomics. The immense utility of the approach came to fore from studies with model system C. elegans, but quickly became applicable with varied research models ranging from in vitro to various in vivo systems. Previously, there have been reports on the refractoriness of the neuronal cells to RNAi mediated gene silencing following which several modulators like eri-1 and lin-15 were described in C. elegans which, when present, would negatively impact the gene knockdown.

Methodology/Principal Findings

Taking a clue from these findings, we went on to screen hypothesis-driven- methodologies towards exploring the efficiency in the process of RNAi under various experimental conditions, wherein these genes would be knocked down preceding to, or concurrently with, the knocking down of a gene of interest. For determining the efficiency of gene knockdown, we chose to study visually stark phenotypes of uncoordinated movement, dumpy body morphology and blistered cuticle obtained by knocking down of genes unc-73, dpy-9 and bli-3 respectively, employing the RNAi-by-feeding protocol in model system C. elegans.

Conclusions/Significance

Our studies led to a very interesting outcome as the results reveal that amongst various methods tested, pre-incubation with eri-1 dsRNA synthesizing bacteria followed by co-incubation with eri-1 and gene-of-interest dsRNA synthesizing bacteria leads to the most efficient gene silencing as observed by the analysis of marker phenotypes. This provides an approach for effectively employing RNAi induced gene silencing while working with different genetic backgrounds including transgenic and mutant strains.     

QSAR and Docking Studies on Capsazepine Derivatives for Immunomodulatory and Anti-Inflammatory Activity

Capsazepine, an antagonist of capsaicin, is discovered by the structure and activity relationship. In previous studies it has been found that capsazepine has potency for immunomodulation and anti-inflammatory activity and emerging as a favourable target in quest for efficacious and safe anti-inflammatory drug. Thus, a 2D quantitative structural activity relationship (QSAR) model against target tumor necrosis factor-α (TNF-α) was developed using multiple linear regression method (MLR) with good internal prediction (r² = 0.8779) and external prediction (r² _pred = 0.5865) using Discovery Studio v3.5 (Accelrys, USA). The predicted activity was further validated by in vitro experiment. Capsazepine was tested in lipopolysaccharide (LPS) induced inflammation in peritoneal mouse macrophages. Anti-inflammatory profile of capsazepine was assessed by its potency to inhibit the production of inflammatory mediator TNF-α. The in vitro experiment indicated that capsazepine is an efficient anti-inflammatory agent. Since, the developed QSAR model showed significant correlations between chemical structure and anti-inflammatory activity, it was successfully applied in the screening of forty-four virtual derivatives of capsazepine, which finally afforded six potent derivatives, CPZ-29, CPZ-30, CPZ-33, CPZ-34, CPZ-35 and CPZ-36. To gain more insights into the molecular mechanism of action of capsazepine and its derivatives, molecular docking and in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) studies were performed. The results of QSAR, molecular docking, in silico ADMET screening and in vitro experimental studies provide guideline and mechanistic scope for the identification of more potent anti-inflammatory & immunomodulatory drug.     

Not all sugars are sweet for banana multiplication. In vitro multiplication,rooting, and acclimatization of banana as influenced by carbon source-concentration interactions

Carbon sources have been considered as one of the most important factors for in vitro multiplication of excised tissues. The type and concentration of sugars are known to influence the success of any in vitro protocol. In the present investigation, the effect of four carbon sources (glucose, fructose, mannitol, and sucrose) used to supplement Murashige and Skoog medium at three concentrations (1, 2, and 3%) was studied with respect to in vitro multiplication, in vitro rooting, and hardening in ‘Silk’ banana. Fructose (2%) followed by sucrose (3%) were found to be most the congenial carbon sources for obtaining the highest shoot multiplication rates. Growth parameters were also found to be superior in the fructose-containing media; however, it performed poorly in terms of root induction. Whereas, medium containing sucrose (3%) supported 100% root induction of in vitro-derived shoots. Plantlets multiplied initially on glucose-containing (1 and 3%) and sucrose-containing (3%) media exhibited superior growth parameters after secondary hardening. We conclude that a change in the rooting media could improve the number of successfully hardened plants under ex vitro conditions. To our knowledge, this is the first report describing the effect of sugars on hardening-related parameters in AAB genome of banana and apparently on any variety of banana.     

Epigenetic Modulation of Intestinal Cholesterol Transporter Niemann-Pick C1-like 1 (NPC1L1) Gene Expression by DNA Methylation

Intestinal NPC1L1 transporter is essential for cholesterol absorption and the maintenance of cholesterol homeostasis in the body. NPC1L1 is differentially expressed along the gastrointestinal tract with very low levels in the colon as compared with the small intestine. This study was undertaken to examine whether DNA methylation was responsible for segment-specific expression of NPC1L1. Treatment of mice with 5-azacytidine (i.p.) resulted in a significant dose-dependent increase in NPC1L1 mRNA expression in the colon. The lack of expression of NPC1L1 in the normal colon was associated with high levels of methylation in the area flanking the 3-kb fragment upstream of the initiation site of the mouse NPC1L1 gene in mouse colon as analyzed by EpiTYPER® MassARRAY®. The high level of methylation in the colon was observed in specific CpG dinucleotides and was significantly decreased in response to 5-azacytidine. Similar to mouse NPC1L1, 5-azacytidine treatment also increased the level of human NPC1L1 mRNA expression in the intestinal HuTu-80 cell line in a dose- and time-dependent manner. Silencing the expression of DNA methyltransferase DNMT1, -2, -3A, and -3B alone by siRNA did not affect NPC1L1 expression in HuTu-80 cells. However, the simultaneous attenuation of DNMT1 and -3B expression caused a significant increase in NPC1L1 mRNA expression as compared with control. Also, in vitro methylation of the human NPC1L1 promoter significantly decreased NPC1L1 promoter activity in human intestinal Caco2 cells. In conclusion, our data demonstrated for the first time that DNA methylation in the promoter region of the NPC1L1 gene appears to be a major mechanism underlying differential expression of NPC1L1 along the length of the gastrointestinal tract.     

Elucidation of the Block to Herpes Simplex Virus Egress in the Absence of Tegument Protein UL16 Reveals a Novel Interaction with VP22

UL16 is a tegument protein of herpes simplex virus (HSV) that is conserved among all members of the Herpesviridae, but its function is poorly understood. Previous studies revealed that UL16 is associated with capsids in the cytoplasm and interacts with the membrane protein UL11, which suggested a “bridging” function during cytoplasmic envelopment, but this conjecture has not been tested. To gain further insight, cells infected with UL16-null mutants were examined by electron microscopy. No defects in the transport of capsids to cytoplasmic membranes were observed, but the wrapping of capsids with membranes was delayed. Moreover, clusters of cytoplasmic capsids were often observed, but only near membranes, where they were wrapped to produce multiple capsids within a single envelope. Normal virion production was restored when UL16 was expressed either by complementing cells or from a novel position in the HSV genome. When the composition of the UL16-null viruses was analyzed, a reduction in the packaging of glycoprotein E (gE) was observed, which was not surprising, since it has been reported that UL16 interacts with this glycoprotein. However, levels of the tegument protein VP22 were also dramatically reduced in virions, even though this gE-binding protein has been shown not to depend on its membrane partner for packaging. Cotransfection experiments revealed that UL16 and VP22 can interact in the absence of other viral proteins. These results extend the UL16 interaction network beyond its previously identified binding partners to include VP22 and provide evidence that UL16 plays an important function at the membrane during virion production.     

Evaluation of a community-based mobile video breastfeeding intervention in Khayelitsha,South Africa: The Philani MOVIE cluster-randomized controlled trial

BackgroundIn South Africa, breastfeeding promotion is a national health priority. Regular perinatal home visits by community health workers (CHWs) have helped promote exclusive breastfeeding (EBF) in underresourced settings. Innovative, digital approaches including mobile video content have also shown promise, especially as access to mobile technology increases among CHWs. We measured the effects of an animated, mobile video series, the Philani MObile Video Intervention for Exclusive breastfeeding (MOVIE), delivered by a cadre of CHWs (“mentor mothers”).Methods and findingsWe conducted a stratified, cluster-randomized controlled trial from November 2018 to March 2020 in Khayelitsha, South Africa. The trial was conducted in collaboration with the Philani Maternal Child Health and Nutrition Trust, a nongovernmental community health organization. We quantified the effect of the MOVIE intervention on EBF at 1 and 5 months (primary outcomes), and on other infant feeding practices and maternal knowledge (secondary outcomes). We randomized 1,502 pregnant women in 84 clusters 1:1 to 2 study arms. Participants’ median age was 26 years, 36.9% had completed secondary school, and 18.3% were employed. Mentor mothers in the video intervention arm provided standard-of-care counseling plus the MOVIE intervention; mentor mothers in the control arm provided standard of care only. Within the causal impact evaluation, we nested a mixed-methods performance evaluation measuring mentor mothers’ time use and eliciting their subjective experiences through in-depth interviews.At both points of follow-up, we observed no statistically significant differences between the video intervention and the control arm with regard to EBF rates and other infant feeding practices [EBF in the last 24 hours at 1 month: RR 0.93 (95% CI 0.86 to 1.01, P = 0.091); EBF in the last 24 hours at 5 months: RR 0.90 (95% CI 0.77 to 1.04, P = 0.152)]. We observed a small, but significant improvement in maternal knowledge at the 1-month follow-up, but not at the 5-month follow-up. The interpretation of the results from this causal impact evaluation changes when we consider the results of the nested mixed-methods performance evaluation. The mean time spent per home visit was similar across study arms, but the intervention group spent approximately 40% of their visit time viewing videos. The absence of difference in effects on primary and secondary endpoints implies that, for the same time investment, the video intervention was as effective as face-to-face counseling with a mentor mother. The videos were also highly valued by mentor mothers and participants. Study limitations include a high loss to follow-up at 5 months after premature termination of the trial due to the COVID-19 pandemic and changes in mentor mother service demarcations.ConclusionsThis trial measured the effect of a video-based, mobile health (mHealth) intervention, delivered by CHWs during home visits in an underresourced setting. The videos replaced about two-fifths of CHWs’ direct engagement time with participants in the intervention arm. The similar outcomes in the 2 study arms thus suggest that the videos were as effective as face-to-face counselling, when CHWs used them to replace a portion of that counselling. Where CHWs are scarce, mHealth video interventions could be a feasible and practical solution, supporting the delivery and scaling of community health promotion services.Trial registrationThe study and its outcomes were registered at clinicaltrials.gov (#{"type":"clinical-trial","attrs":{"text":"NCT03688217","term_id":"NCT03688217"}}NCT03688217) on September 27, 2018.

Maya Adam and colleagues study a video intervention, delivered by community health workers, to promote breastfeeding in South Africa.     

A bacterial effector counteracts host autophagy by promoting degradation of an autophagy component

Beyond its role in cellular homeostasis, autophagy plays anti‐ and promicrobial roles in host–microbe interactions, both in animals and plants. One prominent role of antimicrobial autophagy is to degrade intracellular pathogens or microbial molecules, in a process termed xenophagy. Consequently, microbes evolved mechanisms to hijack or modulate autophagy to escape elimination. Although well‐described in animals, the extent to which xenophagy contributes to plant–bacteria interactions remains unknown. Here, we provide evidence that Xanthomonas campestris pv. vesicatoria (Xcv) suppresses host autophagy by utilizing type‐III effector XopL. XopL interacts with and degrades the autophagy component SH3P2 via its E3 ligase activity to promote infection. Intriguingly, XopL is targeted for degradation by defense‐related selective autophagy mediated by NBR1/Joka2, revealing a complex antagonistic interplay between XopL and the host autophagy machinery. Our results implicate plant antimicrobial autophagy in the depletion of a bacterial virulence factor and unravel an unprecedented pathogen strategy to counteract defense‐related autophagy in plant–bacteria interactions.