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The suicide rate among Asian American, Native Hawaiian, and Pacific Islander (AANHPI) Veterans increased from 2001 to 2020. Identifying regions where suicide rates are elevated and increasing among AANHPI Veterans would inform targeted prevention efforts for members of this cohort. We conducted a population-based retrospective cohort study of 377,833 AANHPI Veterans to examine suicide rates and methods (2005-2019) by United States (US) region and over time (2005-2009, 2010-2014, 2015-2019), using US Veteran Eligibility Trends and Statistics and Joint DoD/VA Mortality Data Repository data. AANHPI Veterans across most regions experienced increases in suicide rates from the earliest to latest period; however, patterns differed by region. Age-adjusted suicide rates increased across all three periods among those in the Northeast and West, but increased, then declined in the Midwest and South. In 2015-2019, the age-adjusted suicide rate among AANHPI Veterans was highest in the Northeast (42.0 per 100,000) and lowest in the West (27.5). However, the highest percentages of AANHPI Veteran suicide deaths in 2005-2019 occurred in the West (39.5%) and South (34.7%), with lower percentages in the Midwest (15.0%) and Northeast (10.8%). Across regions, those ages 18-34 had the highest suicide rates. Firearms were the most frequently used suicide method across regions (44.4%-60.2%), except the Northeast (35.2%), where suffocation was more common (38.3%). Results suggest particular needs for suicide prevention efforts among AANHPI Veterans in the Northeast and to ensure that lethal means safety initiatives for AANHPI Veterans encompass both firearms and suffocation, with some variations in emphasis across regions., Competing Interests: Declaration of Competing Interest Authors were employed by the Department of Veterans Affairs (VA) during the initial analysis and writing of this manuscript. Authors have received funding from the VA Office of Mental Health and Suicide Prevention (Monteith, Schneider, Miller, Gaeddert, Holliday, Spark, Brenner, Hoffmire), VA Health Services Research and Development (Monteith, Schneider, Miller, Gaeddert, Holliday, Spark, Brenner, Hoffmire), VA Rehabilitation Research and Development (Brenner), VA Office of Rural Health (Schneider, Brenner, Spark), VA National Center on Homelessness among Veterans (Holliday, Monteith, Brenner), VA National Center for Patient Safety (Monteith, Hoffmire), VA Office of Women’s Health (Monteith), VA Office of Health Equity (Holliday, Monteith), the National Institutes of Health (Brenner, Holliday, Hoffmire), the Department of Defense (Monteith, Holliday, Brenner, Hoffmire), the American Psychological Association (Monteith), and the State of Colorado (Brenner, Hoffmire). In her current employment with Westat, Dr. Spark has also received funding from the CDC and SAMHSA. Dr. Brenner also reports editorial remuneration from Wolters Kluwer, royalties from the American Psychological Association and Oxford University Press, and consults with sports leagues via her university affiliation., (Published by Elsevier B.V.)

Natural Attenuation (NA) processes have been demonstrated to reduce pollutant loads at different contaminated groundwater sites world-wide and are increasingly considered in contaminated site management concepts. However, data are mainly available for steady state groundwater flow and stable redox conditions as well as pollutants listed in standard regulatory schemes. In this study, the influence of transient groundwater flow and redox conditions on NA was examined at a former gas works site near the river Rhine in Germany. The investigated 78 pollutants included 40 mono- and polyaromatic hydrocarbons (MAHs, PAHs) and 38 NSO-heterocyclic aromatic hydrocarbons (NSO-HET). In the highly polluted areas, the MAHs benzene, indene and indane, the PAHs naphthalene, acenaphthene, 1- and 2-methylnaphthalene and the NSO-HET 2-methylquinoline, carbazole, benzothiophene, dibenzofuran and benzofuran were predominant. Pollutant concentrations decreased with increasing distance from the sources of contamination. At the plume fringes, the MAHs benzene and indane, the PAH acenaphthene, the NSO-HET carbazole, 5-methylbenzothiophene, 2- and 3-methylbenzofuran and 2-methyldibenzofuran were predominant, indicating low retention and slow intrinsic biodegradation of these compounds. The influence of surface water on groundwater level, pollutant concentrations, and redox conditions in the monitoring wells was observed with a permanently installed groundwater sensor. The temporary availability of oxygen was observed at the plume fringes, resulting in aerobic and ferric iron reducing biodegradation processes. Field and laboratory data were used to set-up a groundwater flow and reactive transport model used for quantification of the field mass transfer rates. In conclusion, the study demonstrates that NA is effective under transient flow and redox conditions. A conceptual model and reactive transport simulation can facilitate the interpretation of pronounced fluctuations of pollutant concentration in monitoring wells. Based on the analysis of 78 pollutants, indane, indene and several NSO-HET like carbazole, benzothiophene and 2-methyldibenzofuran are recommended for monitoring at tar oil polluted sites, besides EPA-PAHs and BTEX., (Copyright © 2021 Elsevier B.V. All rights reserved.)

To extend the value of biosensor-SPR in the characterization of DNA recognition by nucleoproteins, we report a comparative analysis of DNA-facilitated target search by two ETS-family transcription factors: Elk1 and ETV6. ETS domains represent an attractive system for developing biosensor-based techniques due to a broad range of physicochemical properties encoded within a highly conserved DNA-binding motif. Building on a biosensor approach in which the protein is quantitatively sequestered and presented to immobilized cognate DNA as nonspecific complexes, we assessed the impact of intrinsic cognate and nonspecific affinities on long-range (intersegmental) target search. The equilibrium constants of DNA-facilitated binding were sensitive to the intrinsic binding properties of the proteins such that their relative specificity for cognate DNA were reinforced when binding occurred by transfer vs. without nonspecific DNA. Direct measurement of association and dissociation kinetics revealed ionic features of the activated complex that evidenced DNA-facilitated dissociation, even though Elk1 and ETV6 harbor only a single DNA-binding surface. At salt concentrations that masked the effects of nonspecific pre-binding at equilibrium, the dissociation kinetics of cognate binding were nevertheless distinct from conditions under which nonspecific DNA was absent. These results further strengthen the significance of long-range DNA-facilitated translocation in the physiologic environment., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Pathogenic variants in the X-linked gene NEXMIF (previously KIAA2022) are associated with intellectual disability (ID), autism spectrum disorder, and epilepsy. We aimed to delineate the female and male phenotypic spectrum of NEXMIF encephalopathy., Methods: Through an international collaboration, we analyzed the phenotypes and genotypes of 87 patients with NEXMIF encephalopathy., Results: Sixty-three females and 24 males (46 new patients) with NEXMIF encephalopathy were studied, with 30 novel variants. Phenotypic features included developmental delay/ID in 86/87 (99%), seizures in 71/86 (83%) and multiple comorbidities. Generalized seizures predominated including myoclonic seizures and absence seizures (both 46/70, 66%), absence with eyelid myoclonia (17/70, 24%), and atonic seizures (30/70, 43%). Males had more severe developmental impairment; females had epilepsy more frequently, and varied from unaffected to severely affected. All NEXMIF pathogenic variants led to a premature stop codon or were deleterious structural variants. Most arose de novo, although X-linked segregation occurred for both sexes. Somatic mosaicism occurred in two males and a family with suspected parental mosaicism., Conclusion: NEXMIF encephalopathy is an X-linked, generalized developmental and epileptic encephalopathy characterized by myoclonic-atonic epilepsy overlapping with eyelid myoclonia with absence. Some patients have developmental encephalopathy without epilepsy. Males have more severe developmental impairment. NEXMIF encephalopathy arises due to loss-of-function variants.

Bioabsorbable barrier membrane is desired in dental medicine for treatment of periodontal diseases caused by different types of bacteria. Bioactive and bioabsorbable bacterial cellulose (BC) is a promising material for such application. However, a key challenge to implement this approach is produce BC membranes selectively oxidized and loaded with a bactericide, in order to modulate bioabsortion time and bactericide effect, respectively. In the present study, the drug model chlorhexidine (CHX) was chosen and NaIO 4 was used as oxidizing agent. To modulate CHX release and efficacy, inclusion complexes of CHX with β-cyclodextrin (CHX:βCD) were synthesized. A linear dependence between degree of oxidation (DO) and oxidant concentration was found (DO = 2.07 + 45 [NaIO 4 ]). CHX has strong chemical interaction with cellulose structure, contributing for its significant retention. The association of membrane oxidation and formation of the inclusion complex with βCD causes a 10-fold increase in CHX release rate compared to unmodified cellulose. Thus, validating the concept that CHX release can be modulated using these two strategies. All membranes loaded with CHX inhibited S. aureus, E. coli and C. albicans growth, but DABC+CHX:βCD showed greater inhibition zone (p < 0.05). That, associated with other results, indicates potential application as bioactive and bioabsorbable membrane., (Copyright © 2020. Published by Elsevier B.V.)

Background: Angiogenesis is implicated in formation of gastrointestinal arteriovenous malformations (AVMs). Angiotensin II signaling is involved in angiogenesis through the vascular endothelial growth factor (VEGF) and angiopoietin-2 pathways. We hypothesized that angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) therapy would be associated with a reduced risk of all-cause gastrointestinal bleeding (GIB) and AVM-associated GIB in patients with left ventricular assist devices (LVADs)., Methods: We reviewed records of all adult patients receiving a continuous-flow LVAD (HeartMate II or HeartWare HVAD) at Johns Hopkins Hospital between January 2004 and December 2014. Of 192 patients, 131 were included for final analyses. Logistic regression analysis adjusting for demographic, cardiovascular, and laboratory variables was used to assess the association of ACEI or ARB therapy with GIB., Results: Of 131 patients, 100 received ACEI or ARB therapy during LVAD support. Of the 31 patients who did not receive ACEI or ARB, 15 experienced GIB (48%), with 9 caused by AVMs (29%). Of 100 patients who received ACEI or ARB therapy, 24 experienced GIB (24%), with 9 caused by AVMs (9%). Logistic regression hazards model demonstrated that ACEI or ARB therapy was independently associated with a reduced risk for all-cause GIB (odds ratio 0.29, 95% confidence interval 0.12-0.72) and AVM-related GIB (odds ratio 0.23, 95% confidence interval 0.07-0.71)., Conclusions: Angiotensin II antagonism is associated with a reduced risk of AVM-related GIB in patients with LVADs. This association is independent of age, sex, blood pressure, renal function, international normalized ratio, LVAD type, and cardiomyopathy etiology., (Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Patients with non-alcoholic fatty liver disease (NAFLD) are thought to be at increased risk of cardiovascular morbidity and mortality. However, the relationships between NAFLD and subclinical myocardial injury or structural heart disease are unknown., Methods: We conducted a cross-sectional analysis of 8668 participants from the Atherosclerosis Risk in Communities (ARIC) Study, who showed no clinical evidence of cardiovascular disease. We used levels of liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST] and gamma-glutamyl transpeptidase [GGT]), in the context of no history of elevated alcohol consumption as non-invasive surrogates of NAFLD. We used highly sensitive cardiac troponin T (hs-cTnT) and N-terminal pro-Brain natriuretic peptide (NT-proBNP) as biomarkers of myocardial damage and function., Results: In this population-based study (mean age 63 years, 60% women, 78% white), higher levels of ALT, AST, and GGT, even within the normal range, were significantly and independently associated with detectable (hs-cTnT >3 ng/L) and elevated (hs-cTnT ⩾14 ng/L) concentrations of hs-cTnT. The adjusted odds ratios (95% confidence interval) for elevated liver enzymes (vs. normal levels) with elevated hs-cTnT were: 1.65 (1.28-2.14) for ALT, 1.90 (1.36-2.68) for AST, and 1.55 (1.13-2.12) for GGT. Furthermore, there was evidence for inverse associations of ALT and AST with NT-proBNP., Conclusions: Our results suggest that elevated liver enzyme levels in the absence of elevated alcohol consumption may be associated with subclinical myocardial injury. The inverse association between NT-proBNP and both ALT and AST supports the recently described metabolic role of natriuretic peptides., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: In the absence of effective treatments for the negative symptom complex of schizophrenia, we explored the effect of 4 consecutive weeks of repetitive transcranial magnetic stimulation (rTMS) exposure (20 sessions) as an add-on treatment to atypical antipsychotics., Methods: Three groups of 17 schizophrenic subjects each were exposed to 20 treatments of either placebo, 1 Hz (100 pulses per day=2000 total) or 10 Hz (1000 pulses per day=20,000 total) rTMS at 110% motor threshold over the left dorsolateral prefrontal cortex, while being maintained on their atypical antipsychotic. Subjects were evaluated at baseline, weeks 2 and 4, and at 4-week follow-up after the last treatment., Results: The primary outcome measure (change in Scale for Assessment of Negative Symptoms score) showed a statistically significant drop at weeks 2, 4, and 8 for the high frequency (10 Hz) group, but not the 1 Hz or placebo groups. Secondary outcome measures of the Wisconsin Card Sorting Test and SF-36 did not demonstrate any significant change., Conclusions: rTMS may serve as a relatively noninvasive treatment of the negative and neurocognitive deficits associated with schizophrenia.