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Disparities in maternal-child health outcomes by race and ethnicity highlight structural differences in the opportunity for optimal health in the United States. Examples of these differences include access to state-level social policies that promote maternal-child health. States vary in their racial and ethnic composition as a result of the complex history of policies and laws related to slavery, Indigenous genocide and relocation, segregation, immigration, and settlement in the United States. States also vary in the social policies they enact. As a result, correlations exist between the demographic makeup of a state's population and the presence or absence of social policies in that state. These correlations become a mechanism by which racial and ethnic disparities in maternal-child health outcomes can operate. In this commentary, we use the example of 3 labor-related policies actively under consideration at state and federal levels (paid parental leave, paid sick leave, and reasonable accommodations during pregnancy) to demonstrate how correlations between state demographics and presence of these state policies could cause or exacerbate racial and ethnic disparities in maternal-child health outcomes. We conclude with a call for researchers to consider how the geographic distribution of racialized populations and state policies could contribute to maternal-child health disparities. [ABSTRACT FROM AUTHOR]

Purpose: To investigate potential attenuation of healthy worker biases in populations in which healthy women of reproductive age opt out of the workforce to provide childcare.Methods: We used 2013-2015 data from 120,928 U.S. women and men aged 22-44 years participating in the Gallup-Healthways Well-Being Index. We used logistic regression to estimate adjusted prevalence odds ratios (PORs) and 95% confidence intervals (CIs) for associations between health and workforce nonparticipation.Results: Women and men reporting poor health were more likely to be out of the workforce than individuals reporting excellent health (POR: 3.7, 95% CI: 3.2-4.2; POR: 6.7, 95% CI: 5.7-7.8, respectively), suggesting potential for healthy worker bias. For women (P < .001) but not men (P = .30), the strength of this association was modified by number of children in the home: POR: 7.3 (95% CI: 5.8-9.1) for women with no children, decreasing to POR: 0.9 (95% CI: 0.6-1.5) for women with four or more children.Conclusions: These results are consistent with attenuation of healthy worker biases when healthy women opt out of the workforce to provide childcare. Accordingly, we might expect the magnitude of these biases to vary with the proportion of women with differing numbers of children in the population. [ABSTRACT FROM AUTHOR]

We performed a panoramic analysis on both human nonalcoholic steatohepatitis (NASH) microarray data and microarray/RNA-seq data from various mouse models of nonalcoholic fatty liver disease NASH/NAFLD with total 4249 genes examined and made the following findings: (i) human NASH and NAFLD mouse models upregulate both cytokines and chemokines; (ii) pathway analysis indicated that human NASH can be classified into metabolic and immune NASH; methionine- and choline-deficient (MCD)+high-fat diet (HFD), glycine N-methyltransferase deficient (GNMT-KO), methionine adenosyltransferase 1A deficient (MAT1A-KO), and HFCD (high-fat-cholesterol diet) can be classified into inflammatory, SAM accumulation, cholesterol/mevalonate, and LXR/RXR-fatty acid β-oxidation NAFLD, respectively; (iii) canonical and noncanonical inflammasomes play differential roles in the pathogenesis of NASH/NAFLD; (iv) trained immunity (TI) enzymes are significantly upregulated in NASH/NAFLD; HFCD upregulates TI enzymes more than cytokines, chemokines, and inflammasome regulators; (v) the MCD+HFD is a model with the upregulation of proinflammatory cytokines and canonical and noncanonical inflammasomes; however, the HFCD is a model with upregulation of TI enzymes and lipid peroxidation enzymes; and (vi) caspase-11 and caspase-1 act as upstream master regulators, which partially upregulate the expressions of cytokines, chemokines, canonical and noncanonical inflammasome pathway regulators, TI enzymes, and lipid peroxidation enzymes. Our findings provide novel insights on the synergies between hyperlipidemia and hypomethylation in establishing TI and promoting inflammation in NASH and NAFLD progression and novel targets for future therapeutic interventions for NASH and NAFLD, metabolic diseases, transplantation, and cancers. [ABSTRACT FROM AUTHOR]

Purpose: To examine the association betweenantineoplastic drug (AD) handling and risk of miscarriage.Methods: Nurses' Health Study-3 participants self-reported AD administration and engineering controls (ECs) and personal protective equipment (PPE) use at baseline. We estimated the hazard ratio (HR) of miscarriage in relation to baseline AD handling using multivariable Cox proportional regression.Results: Overall, 2440 nurses reported 3327 pregnancies, with 550 (17%) ended in miscarriages. Twelve percent of nurses self-reported currently handling AD and 28% previously handling AD. Compared with nurses who never handled AD, nurses who handled AD at baseline had an adjusted HR of miscarriage of 1.26 (95% confidence interval [CI], 0.97-1.64). This association was stronger after 12-weeks gestation (HR=2.39 [95% CI, 1.13-5.07]). Nurses who did not always use gloves had HR of 1.51 (95% CI, 0.91-2.51) compared with 1.19 (95% CI, 0.89-1.60) for those always using gloves; nurses who did not always use gowns had HR of 1.32 (95% CI, 0.95-1.83) compared with 1.19 (95% CI, 0.81-1.75) for nurses always using gowns.Conclusions: We observed a suggestive association between AD handling and miscarriage, particularly among nurses who did not consistently use PPE and EC with stronger associations for second trimester losses. [ABSTRACT FROM AUTHOR]

Background: The immune mechanisms underlying low-intensity ultrasound- (LIUS-) mediated suppression of inflammation and tumorigenesis remain poorly determined.Methods: We used microarray datasets from the NCBI GEO DataSet repository and conducted comprehensive data-mining analyses, where we examined the gene expression of 1376 innate immune regulators (innatome genes (IGs) in cells treated with LIUS.Results: We made the following findings: (1) LIUS upregulates proinflammatory IGs and downregulates metastasis genes in cancer cells, and LIUS upregulates adaptive immunity pathways but inhibits danger-sensing and inflammation pathways and promote tolerogenic differentiation in bone marrow (BM) cells. (2) LIUS upregulates IGs encoded for proteins localized in the cytoplasm, extracellular space, and others, but downregulates IG proteins localized in nuclear and plasma membranes, and LIUS downregulates phosphatases. (3) LIUS-modulated IGs act partially via several important pathways of reactive oxygen species (ROS), reverse signaling of immune checkpoint receptors B7-H4 and BTNL2, inflammatory cytokines, and static or oscillatory shear stress and heat generation, among which ROS is a dominant mechanism. (4) LIUS upregulates trained immunity enzymes in lymphoma cells and downregulates trained immunity enzymes and presumably establishes trained tolerance in BM cells. (5) LIUS modulates chromatin long-range interactions to differentially regulate IGs expression in cancer cells and noncancer cells.Conclusions: Our analysis suggests novel molecular mechanisms that are utilized by LIUS to induce tumor suppression and inflammation inhibition. Our findings may lead to development of new treatment protocols for cancers and chronic inflammation. [ABSTRACT FROM AUTHOR]

Objective To assess the potential impact of missing data on body mass index (BMI) on the association between prepregnancy obesity and specific birth defects. Methods Data from the National Birth Defects Prevention Study (NBDPS) were analyzed. We assessed the factors associated with missing BMI data among mothers of infants without birth defects. Four analytic methods were then used to assess the impact of missing BMI data on the association between maternal prepregnancy obesity and three birth defects; spina bifida, gastroschisis, and cleft lip with/without cleft palate. The analytic methods were: (1) complete case analysis; (2) assignment of missing values to either obese or normal BMI; (3) multiple imputation; and (4) probabilistic sensitivity analysis. Logistic regression was used to estimate crude and adjusted odds ratios (aOR) and 95 % confidence intervals (CI). Results Of NBDPS control mothers 4.6 % were missing BMI data, and most of the missing values were attributable to missing height (~90 %). Missing BMI data was associated with birth outside of the US (aOR 8.6; 95 % CI 5.5, 13.4), interview in Spanish (aOR 2.4; 95 % CI 1.8, 3.2), Hispanic ethnicity (aOR 2.0; 95 % CI 1.2, 3.4), and <12 years education (aOR 2.3; 95 % CI 1.7, 3.1). Overall the results of the multiple imputation and probabilistic sensitivity analysis were similar to the complete case analysis. Conclusions Although in some scenarios missing BMI data can bias the magnitude of association, it does not appear likely to have impacted conclusions from a traditional complete case analysis of these data. [ABSTRACT FROM AUTHOR]

Abstract: Background: Obstructive sleep apnea (OSA) in adults has been associated with hypertension, low baroreflex sensitivity (BRS), a delayed heart rate response to changing blood pressure (heart period delay [HPD]), and increased blood pressure variability (BPV). Poor BRS may contribute to hypertension by impairing the control of blood pressure (BP), with increased BPV and HPD. Although children with OSA have elevated BP, there are scant data on BRS, BPV, or HPD in this group. Methods: 105 children ages 7–12years referred for assessment of OSA and 36 nonsnoring controls were studied. Overnight polysomnography (PSG) was performed with continuous BP monitoring. Subjects were assigned to groups according to their obstructive apnea–hypopnea index (OAHI): primary snoring (PS) (OAHI ⩽1event/h), mild OSA (OAHI>1–⩽5events/h) and moderate/severe (MS) OSA (OAHI>5events/h). BRS and HPD were calculated using cross spectral analysis and BPV using power spectral analysis. Results: Subjects with OSA had significantly lower BRS (p <.05 for both) and a longer HPD (PS and MS OSA, p <.01; mild OSA, p <.05) response to spontaneous BP changes compared with controls. In all frequencies of BPV, the MS group had higher power compared with the control and PS groups (low frequency [LF], p <.05; high frequency [HF], p <.001). Conclusions: Our study demonstrates reduced BRS, longer HPD, and increased BPV in subjects with OSA compared to controls. This finding suggests that children with OSA have altered baroreflex function. Longitudinal studies are required to ascertain if this dampening of the normal baroreflex response can be reversed with treatment. [Copyright &y& Elsevier]

Chagas disease is a deadly infection caused by the protozoan parasite Trypanosoma cruzi. Afflicting approximately 8 million people in Latin America, Chagas disease is now becoming a serious global health problem proliferating beyond the traditional geographical borders, mainly because of human and vector migration. Because the disease is endemic in low-resource areas, industrial drug development has been lethargic. The chronic form remains incurable, there are no vaccines, and 2 existing drugs for the acute form are toxic and have low efficacy. Here we report the efficacy of a small molecule, VNI, including evidence of its effectiveness against chronic Chagas disease. VNI is a potent experimental inhibitor of T. cruzi sterol 14α-demethylase. Nontoxic and highly selective, VNI displays promising pharmacokinetics and administered orally to mice at 25 mg/kg for 30 days cures, with 100% cure rate and 100% survival, the acute and chronic T. cruzi infection. [ABSTRACT FROM AUTHOR]

Abstract: Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence, the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association (STREGA) studies initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy–Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed, but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis. [Copyright &y& Elsevier]

It has been shown that the invasive trypomastigote forms of Trypanosoma cruzi use and modulate components of the extracellular matrix (ECM) during the initial process of infection. Infective trypomastigotes up-regulate the expression of laminin γ-1 (LAMC1) and thrombospondin (THBS1) to facilitate the recruitment of trypomastigotes to enhance cellular infection. Silencing the expression of LAMC1 and THBS1 by stable RNAi dramatically reduces trypanosome infection. T. cruzi gp83, a ligand that mediates the attachment of trypanosomes to cells to initiate infection, up-regulates LAMC1 expression to enhance cellular infection. Infective trypomastigotes interact with LAMC1 through galectin-3 (LGALS3), a human lectin, to enhance cellular infection. Silencing the expression of LGALS3 also reduces cellular infection. Some trypanosome surface molecules also interact with the ECM to facilitate infection. Despite the role of the ECM in T. cruzi infection, almost nothing is known about the ECM interactome networks operating in the process of T. cruzi infection. In this mini review, we critically analyze and discuss the regulation of the ECM by T. cruzi and its gp83 ligand, and present the first elucidation of the human ECM interactome network, regulated by T. cruzi and its gp83 ligand, to facilitate cellular infection. The elucidation of the human ECM interactome regulated by T. cruzi is critically important to the understanding of the molecular pathogenesis of T. cruzi infection and developing novel approaches of intervention in Chagas' disease.