Underlying mechanisms by which exposures to toxic metals/metalloids impact obesity and type 2 diabetes (T2DM) risk remain largely unknown. Gut microbiota have been strongly associated with cardiometabolic risk. To assess relationships between high metal exposures, gut dysbiosis, and metabolic dysregulation, we analyzed associations among gut microbiome taxa, dichotomized metal levels (arsenic, lead, mercury, cadmium), clinical measures (BMI, fasting blood glucose, blood pressure), and diagnoses (hypertension, obesity, diabetes) in 178 African-origin adults (52% female, mean age = 43.0 ± 6.4 years) from Ghana, South Africa, Jamaica, Seychelles, and USA. High vs. low lead and arsenic levels had a significant effect on beta diversity (p < 0.05). Seventy-one taxa were associated with high lead levels: 30 with elevated BMI, 22 with T2DM, and 23 with elevated fasting blood glucose (p < 0.05); 115 taxa were associated with high arsenic levels: 32 with elevated BMI, 33 with T2DM, and 26 with elevated blood glucose (p < 0.05). Porphyrin metabolism was the most enriched metabolic pathway in taxa associated with higher lead and arsenic exposure. These data provide the first findings from African-origin adults that demonstrate the association between the gut microbiome with lead and arsenic exposure and obesity and T2DM risk.

OBJECTIVE Metal and metalloid exposures (hereafter “metals”) are associated with adverse health outcomes, including type 2 diabetes; however, previous studies were largely cross-sectional or underpowered. Furthermore, underserved racial and ethnic groups are underrepresented in environmental health research despite having higher rates of type 2 diabetes and a greater risk of metal exposures. Consequently, we evaluated continuous glycemic traits in relation to baseline urinary toxic metal, essential metal, and metal mixtures in a cohort of Mexican American adults. RESEARCH DESIGN AND METHODS A total of 510 participants were selected based upon self-reported diabetes status and followed over 3 years. Urinary metals were assessed at baseline. Linear mixed-effects models were used to estimate per-month changes in hemoglobin A1c, fasting plasma glucose, and postload glucose in relation to urinary metal levels. Multiple statistical approaches were used to assess the associations between glycemic traits and metal mixtures. RESULTS After adjustment, higher urinary levels of arsenic, selenium, copper, molybdenum, nickel, and tin were associated with faster increases in measures of glycemia. The toxic metal mixture composed of arsenic, lead, cadmium, nickel, and tin was associated with faster increases in postload glucose. Using postload glucose criteria, highest versus lowest arsenic was predicted to accelerate conversion of normoglycemia to prediabetes and diabetes by 23 and 65 months, respectively. CONCLUSIONS In this underrepresented, high-risk Mexican American population, exposure to toxic metals and alterations in essential metal homeostasis were associated with faster increases in glycemia over time that may accelerate type 2 diabetes development.

The full-length cDNA and gDNA sequences of a polyketide synthase gene, termed pks-pa, of Phomopsis asparagi (the fungal pathogen causing the asparagus stem blight), were obtained by RT-PCR, 5'/3'-RACE, PCR and TAIL-PCR. The full-length pks-pa gDNA sequence is 9.336 kb, comprising 5 introns and 6 exons. Sequence alignment revealed a 28-nucleotide difference in polyketide synthase genes between P. asparagi and its closely related species. Phylogenetic analysis indicated that pks-pa is evolutionarily distinct from the polyketide synthases of other fungal species in the same genus. Protein sequence analysis and structural prediction suggested that pks-pa is a hydrophilic protein composed of alpha, beta, turns, coil, alpha amphipathic, beta amphipathic and flexible regions. To confirm the function of pks-pa, a knockout plasmid was used to generate pks-pa knockout transformants in the P. asparagi XT3 isolate. Pathogenic assays showed that loss of pks-pa had no effect on P. asparagi virulence, but significantly reduced pigment production compared with wild-type P. asparagi isolates. These results indicate that pks-pa is required for pigment production, but not P. asparagi virulence.

Arsenic, cadmium, and lead are toxic elements that widely contaminate our environment. These toxicants are associated with acute and chronic health problems, and evidence suggests that minority communities, including Hispanic/Latino Americans, are disproportionately exposed. Few studies have assessed culturally specific predictors of exposure to understand the potential drivers of racial/ethnic exposure disparities. We sought to evaluate acculturation measures as predictors of metal/metalloid (hereafter “metal”) concentrations among Mexican American adults to illuminate potential exposure sources that may be targeted for interventions. As part of a longitudinal cohort, 510 adults, aged 35 to 69 years, underwent baseline interview, physical examination, and urine sample collection. Self-reported acculturation was assessed across various domains using the Short Acculturation Scale for Hispanics (SASH). Multivariable linear regression was used to assess associations between acculturation and urinary concentrations of arsenic, cadmium, and lead. Ordinal logistic regression was utilized to assess associations between acculturation and a metal mixture score. Lastly, best subset selection was used to build a prediction model for each toxic metal with a combination of the acculturation predictors. After adjustment, immigration factors were positively associated with arsenic and lead concentrations. For lead alone, English language and American media and food preferences were associated with lower levels. Immigration and parental heritage from Mexico were positively associated with the metal mixture, while preferences for English language, media, and food were negatively associated. Acculturation-related predictors of exposure provide information about potential sources of toxic metals, including international travel, foods, and consumer products. The findings in this research study provide information to empower future efforts to identify and address specific acculturation-associated toxicant exposures in order to promote health equity through clinical guidance, patient education, and public policy.

Background: We previously reported that the HMGB1/TLR4 axis promoted inflammation during the acute phase of intracerebral hemorrhage. Given that this phase is known to involve neuronal pyroptosis and neuroinflammation, here we explore whether HMGB1/TLR signaling activate inflammasome and pyroptosis after intracerebral hemorrhage. Methods: Autologous blood was injected into Sprague-Dawley rats to induce intracerebral hemorrhage. Neurological deficits were assessed using a modified neurological severity score. These expression and localization of NLRP1 and NLRP3 inflammasomes, as well as the levels of pyroptosis and pyroptosis-associated proteins were assessed using Western blot or immunocytochemistry. These experiments were repeated in animals that received treatment with short interfering RNAs against NLRP1 or NLRP3, with HMGB1 inhibitor ethyl pyruvate or TLR4 inhibitor TAK-242. Results: Intracerebral hemorrhage upregulated NLRP1 and NLRP3 in the ipsilateral striatum and increased the proportions of these cells that were pyroptosis-positive. Additionally, the levels of caspase protein family (e.g., pro-caspase-1 and caspase-1), apoptosis-associated speck-like protein (ASC), pro-interleukin-1 beta (IL-1 beta), and IL-1 beta were also elevated. These effects on pyroptosis and associated neurological deficit, were partially reversed by knockdown of NLRP1 or NLRP3, or by inhibition of HMGB1 or TLR4. Inhibition of HMGB1 or TLR4 resulted in the downregulation NLRP3 but not NLRP1. Conclusions: The HMGB1/TLR4 signaling may activate the NLRP3 inflammasome during the acute phase of intracerebral hemorrhage, resulting in the inflammatory process known as pyroptosis. These insights suggest potential therapeutic targets for the mitigation tissue injury and associated neurological deficits following hemorrhagic stroke.

Multiple social and structural determinants of health undoubtedly contribute to the marked racial/ethnic-, gender-, and socioeconomic-based disparities in endocrine health; however, the contribution of environmental injustice is vastly underappreci-ated. Indeed, those groups disproportionately burdened by endocrine disorders are often exposed to higher levels of various EDCs, including PCBs, phthalates, bisphe-nols, OC pesticides, air pollutants, PFASs, toxic metals/metalloids, and BFRs. Furthermore, the contribution of disparate exposures to health disparities is likely underestimated because of a paucity of data examining the adverse effects of com-bined EDC exposures. As such, health equity requires interventions to address envi-ronmental injustice. Such approaches must include a complementary array of individual action and public policy,127 the latter of which is inadequately used.128 Based on the Developmental Origins of Health and Disease hypothesis that posits long-term health risks imposed by stressors during sensitive developmental windows (including EDC exposures), it is essential that interventions be targeted to those most vulnerable, including pregnant mothers and infants, among others. However, it is also critical to recognize that EDC exposures and their disproportionate burden on low in-come and communities of color is a systemic problem for which individual action is insufficient. Rather, policy interventions are required, including robust efforts to iden-tify EDCs before they enter commerce, eliminate EDCs already in use, mitigate contaminated sites, and develop socially just policies that end the discriminatory siting of polluting industries. Vigorously pursued, such efforts have the potential to improve endocrine health equity while reducing the burden of disease for everyone.

The toll of multiple endocrine disorders has increased substantially in recent decades, and marginalized populations bear a disproportionate burden of disease. Because of the significant individual and societal impact of these conditions, it is essential to identify and address all modifiable risk factors contributing to these disparities . Abundant evidence now links endocrine dysfunction with exposure to endocrine-disrupting chemicals (EDCs), with greater exposures to multiple EDCs occurring among vulnerable groups, such as racial/ethnic minorities, those with low incomes, and others with high endocrine disease burdens. Identifying and eliminating EDC exposures is an essential step in achieving endocrine health equity.

Using next-generation sequencing on vesicular swab and serum from swine from the USA exhibiting lameness and vesicles, porcine pegivirus (PPgV) was first identified and genetically characterized in the United States. Further screening using RT-PCR revealed that 24 of 159 (15.1%) serum samples were positive for PPgV. Future studies are needed to understand clinical impacts of the virus.

When mounted on the skin, modern sensors, circuits, radios, and power supply systems have the potential to provide clinical-quality health monitoring capabilities for continuous use, beyond the confines of traditional hospital or laboratory facilities. The most well-developed component technologies are, however, broadly available only in hard, planar formats. As a result, existing options in system design are unable to effectively accommodate integration with the soft, textured, curvilinear, and time-dynamic surfaces of the skin. Here, we describe experimental and theoretical approaches for using ideas in soft microfluidics, structured adhesive surfaces, and controlled mechanical buckling to achieve ultralow modulus, highly stretchable systems that incorporate assemblies of high-modulus, rigid, state-of-the-art functional elements. The outcome is a thin, conformable device technology that can softly laminate onto the surface of the skin to enable advanced, multifunctional operation for physiological monitoring in a wireless mode.

The current A(H1N1) flu has showed sub-population dependent susceptibility and fatality as early as April and May of 2009 in its first wave of spreading. After the pandemic outbreak spreads globally for more than seven months, the subpopulation dependence of this flu, including ethnicity, age and gender selectivity, has been recognized by several research groups. This paper attempts to discussed how to identify ethnic selectivity from the released data by WHO relevant to this ongoing flu, review some recently published papers describing the presence of ethnic differences in susceptibilities to the H1N1 flu virus and further raised an argument that ethnic differences in  susceptibilities to a virus might be a piece of evidence reflecting a weak virulence of that specific virus.