Unexpected transformation of dissolved phenols to toxic dicarbonyls by hydroxyl radicals and UV light.

Water treatment systems frequently use strong oxidants or UV light to degrade chemicals that pose human health risks. Unfortunately, these treatments can result in the unintended transformation of organic contaminants into toxic products. We report an unexpected reaction through which exposure of phenolic compounds to hydroxyl radicals (•OH) or UV light results in the formation of toxic α,β-unsaturated enedials and oxoenals. We show that these transformation products damage proteins by reacting with lysine and cysteine moieties. We demonstrate that phenolic compounds react with •OH produced by the increasingly popular UV/hydrogen peroxide (H2O2) water treatment process or UV light to form toxic enedials and oxoenals. In addition to raising concerns about potential health risks of oxidative water treatment, our findings suggest the potential for formation of these toxic compounds in sunlit surface waters, atmospheric water, and living cells. For the latter, our findings may be particularly relevant to efforts to understand cellular damage caused by in vivo production of reactive oxygen species. In particular, we demonstrate that exposure of the amino acid tyrosine to •OH yields an electrophilic enedial product that undergoes cross-linking reaction with both lysine and cysteine residues

Physical Condition, Sex, and Age-Class of Eastern Red-Backed Salamanders ( Plethodon cinereus

Nonforested habitats such as open fields and pastures have been considered unsuitable for desiccation-prone woodland salamanders such as the Eastern Red-backed Salamander (Plethodon cinereus). Recent research has suggested that Plethodon cinereus may not only disperse across but also reside within open habitats including fields, meadows, and pastures. However, presence and high densities of P. cinereus within agriculturally disturbed habitats may be misleading if these populations exhibit atypical demographic characteristics or decreased physical condition relative to forest populations. We surveyed artificial cover boards from 2004-2005 to compare physical condition, sex ratios, and age-class structure of P. cinereus among woodland, woodland-meadow edge, silvopasture, and meadow sites in the central Appalachian Mountains of southern West Virginia. Physical condition of salamanders was not significantly different among the four habitats. Furthermore, adult sex ratios of P. cinereus typically were not significantly different from 1 : 1 and were similar between forested and non-forested sites, although populations within silvopastures were biased towards females. However, adult salamanders were significantly more abundant than juveniles in all habitat types, with differences most pronounced within meadow habitats. Our study indicates that relatively small, non-forested habitats such as silvopastures and meadows may not adversely affect the overall physical condition or sex ratios of Plethodon cinereus. However, the paucity of juveniles within disturbed meadows indicates that these agriculturally modified habitats may negatively impact reproduction or that immature salamanders are at a physiological or competitive disadvantage in comparison to adults, particularly when surface cover is limited

Covalent targeting of the vacuolar H+-ATPase activates autophagy via mTORC1 inhibition.

Autophagy is a lysosomal degradation pathway that eliminates aggregated proteins and damaged organelles to maintain cellular homeostasis. A major route for activating autophagy involves inhibition of the mTORC1 kinase, but current mTORC1-targeting compounds do not allow complete and selective mTORC1 blockade. Here, we have coupled screening of a covalent ligand library with activity-based protein profiling to discover EN6, a small-molecule in vivo activator of autophagy that covalently targets cysteine 277 in the ATP6V1A subunit of the lysosomal v-ATPase, which activates mTORC1 via the Rag guanosine triphosphatases. EN6-mediated ATP6V1A modification decouples the v-ATPase from the Rags, leading to inhibition of mTORC1 signaling, increased lysosomal acidification and activation of autophagy. Consistently, EN6 clears TDP-43 aggregates, a causative agent in frontotemporal dementia, in a lysosome-dependent manner. Our results provide insight into how the v-ATPase regulates mTORC1, and reveal a unique approach for enhancing cellular clearance based on covalent inhibition of lysosomal mTORC1 signaling

Health screenings administered during the domestic medical examination of refugees and other eligible immigrants in nine US states, 2014-2016: A cross-sectional analysis.

BACKGROUND: Refugees and other select visa holders are recommended to receive a domestic medical examination within 90 days after arrival to the United States. Limited data have been published on the coverage of screenings offered during this examination across multiple resettlement states, preventing evaluation of this voluntary program\u27s potential impact on postarrival refugee health. This analysis sought to calculate and compare screening proportions among refugees and other eligible populations to assess the domestic medical examination\u27s impact on screening coverage resulting from this examination. METHODS AND FINDINGS: We conducted a cross-sectional analysis to summarize and compare domestic medical examination data from January 2014 to December 2016 from persons receiving a domestic medical examination in seven states (California, Colorado, Minnesota, New York, Kentucky, Illinois, and Texas); one county (Marion County, Indiana); and one academic medical center in Philadelphia, Pennsylvania. We analyzed screening coverage by sex, age, nationality, and country of last residence of persons and compared the proportions of persons receiving recommended screenings by those characteristics. We received data on disease screenings for 105,541 individuals who received a domestic medical examination; 47% were female and 51.5% were between the ages of 18 and 44. The proportions of people undergoing screening tests for infectious diseases were high, including for tuberculosis (91.6% screened), hepatitis B (95.8% screened), and human immunodeficiency virus (HIV; 80.3% screened). Screening rates for other health conditions were lower, including mental health (36.8% screened). The main limitation of our analysis was reliance on data that were collected primarily for programmatic rather than surveillance purposes. CONCLUSIONS: In this analysis, we observed high rates of screening coverage for tuberculosis, hepatitis B, and HIV during the domestic medical examination and lower screening coverage for mental health. This analysis provided evidence that the domestic medical examination is an opportunity to ensure newly arrived refugees and other eligible populations receive recommended health screenings and are connected to the US healthcare system. We also identified knowledge gaps on how screenings are conducted for some conditions, notably mental health, identifying directions for future research

Health of Special Immigrant Visa holders from Iraq and Afghanistan after arrival into the United States using Domestic Medical Examination data, 2014-2016: A cross-sectional analysis.

BACKGROUND: Since 2008, the United States has issued between 2,000 and 19,000 Special Immigrant Visas (SIV) annually, with the majority issued to applicants from Iraq and Afghanistan. SIV holders (SIVH) are applicants who were employed by, or on behalf of, the US government or the US military. There is limited information about health conditions in SIV populations to help guide US clinicians caring for SIVH. Thus, we sought to describe health characteristics of recently arrived SIVH from Iraq and Afghanistan who were seen for domestic medical examinations. METHODS AND FINDINGS: This cross-sectional analysis included data from Iraqi and Afghan SIVH who received a domestic medical examination from January 2014 to December 2016. Data were gathered from state refugee health programs in seven states (California, Colorado, Illinois, Kentucky, Minnesota, New York, and Texas), one county, and one academic medical center and included 6,124 adults and 4,814 children. Data were collected for communicable diseases commonly screened for during the exam, including tuberculosis (TB), hepatitis B, hepatitis C, malaria, strongyloidiasis, schistosomiasis, other intestinal parasites, syphilis, gonorrhea, chlamydia, and human immunodeficiency virus, as well as elevated blood lead levels (EBLL). We investigated the frequency and proportion of diseases and whether there were any differences in selected disease prevalence in SIVH from Iraq compared to SIVH from Afghanistan. A majority of SIV adults were male (Iraqi 54.0%, Afghan 58.6%) and aged 18-44 (Iraqi 86.0%, Afghan 97.7%). More SIV children were male (Iraqi 56.2%, Afghan 52.2%) and aged 6-17 (Iraqi 50.2%, Afghan 40.7%). The average age of adults was 29.7 years, and the average age for children was 5.6 years. Among SIV adults, 14.4% were diagnosed with latent tuberculosis infection (LTBI), 63.5% were susceptible to hepatitis B virus (HBV) infection, and 31.0% had at least one intestinal parasite. Afghan adults were more likely to have LTBI (prevalence ratio [PR]: 2.0; 95% confidence interval [CI] 1.5-2.7) and to be infected with HBV (PR: 4.6; 95% CI 3.6-6.0) than Iraqi adults. Among SIV children, 26.7% were susceptible to HBV infection, 22.1% had at least one intestinal parasite, and 50.1% had EBLL (≥5 mcg/dL). Afghan children were more likely to have a pathogenic intestinal parasite (PR: 2.7; 95% CI 2.4-3.2) and EBLL (PR: 2.0; 95% CI 1.5-2.5) than Iraqi children. Limitations of the analysis included lack of uniform health screening data collection across all nine sites and possible misclassification by clinicians of Iraqi and Afghan SIVH as Iraqi and Afghan refugees, respectively. CONCLUSION: In this analysis, we observed that 14% of SIV adults had LTBI, 27% of SIVH had at least one intestinal parasite, and about half of SIV children had EBLL. Most adults were susceptible to HBV. In general, prevalence of infection was higher for most conditions among Afghan SIVH compared to Iraqi SIVH. The Centers for Disease Control and Prevention (CDC) Guidelines for the US Domestic Medical Examination for Newly Arriving Refugees can assist state public health departments and clinicians in the care of SIVH during the domestic medical examination. Future analyses can explore other aspects of health among resettled SIV populations, including noncommunicable diseases and vaccination coverage

Inspiring Minds, Exploring Science with Project SCORE Curriculum

Corresponding author (Pharmacy Administration): Tess Johnson, [email protected]://egrove.olemiss.edu/pharm_annual_posters_2022/1009/thumbnail.jp

Health Matters: Student-Developed Research Questions by Project SCORE Students

Corresponding author (Health, Exercise Science, and Recreation Management): Melissa Presley, [email protected]://egrove.olemiss.edu/pharm_annual_posters_2022/1015/thumbnail.jp

Metabolomic Markers of Phthalate Exposure in Plasma and Urine of Pregnant Women

Phthalates are known endocrine disruptors and found in almost all people with several associated adverse health outcomes reported in humans and animal models. Limited data are available on the relationship between exposure to endocrine disrupting chemicals and the human metabolome. We examined the relationship of metabolomic profiles in plasma and urine of 115 pregnant women with eleven urine phthalate metabolites measured at 26 weeks of gestation to identify potential biomarkers and relevant pathways. Targeted metabolomics was performed by selected reaction monitoring liquid chromatography and triple quadrupole mass spectrometry to measure 415 metabolites in plasma and 151 metabolites in urine samples. We have chosen metabolites with the best defined peaks for more detailed analysis (138 in plasma and 40 in urine). Relationship between urine phthalate metabolites and concurrent metabolomic markers in plasma and urine suggested potential involvement of diverse pathways including lipid, steroid, and nucleic acid metabolism and enhanced inflammatory response. Most of the correlations were positive for both urine and plasma, and further confirmed by regression and PCA analysis. However, after the FDR adjustment for multiple comparisons, only 9 urine associations remained statistically significant (q-values 0.0001–0.0451), including Nicotinamide mononucleotide, Cysteine T2, Cystine, and L-Aspartic acid. Additionally, we found negative associations of maternal pre-pregnancy body mass index (BMI) with more than 20 metabolomic markers related to lipid and amino-acid metabolism and inflammation pathways in plasma (p = 0.01–0.0004), while Mevalonic acid was positively associated (p = 0.009). Nicotinic acid, the only significant metabolite in urine, had a positive association with maternal BMI (p = 0.002). In summary, when evaluated in the context of metabolic pathways, the findings suggest enhanced lipid biogenesis, inflammation and altered nucleic acid metabolism in association with higher phthalate levels. These results provide new insights into the relationship between phthalates, common in most human populations, and metabolomics, a novel approach to exposure and health biomonitoring

Serials Spoken Here–Reports of Conferences, Institutes and Seminars

This quarter's column offers a report from the Acquisitions Institute at Timberline Lodge, held May 14–17, 2016, in Timberline Lodge, Oregon, and also provides coverage of multiple sessions from the Kraemer Copyright Conference, held June 6–7, 2016, in Colorado Springs, Colorado. Some reports are collected, as well, from the NASIG Annual Conference, held June 9–12, 2016, in Albuquerque, New Mexico, and the American Library Association (ALA) Annual Conference, held June 23–28, 2016, in Orlando, Florida. Lastly, there is a report from the International Federation of Library Associations and Institutions (IFLA) World Library and Information Congress, held August 13–19, 2016, in Columbus, Ohio. Topics covered include open access, linked data, copyright, text mining, e-resource management, and digitization