Lower Serum Testosterone Associated with Elevated Polychlorinated Biphenyl Concentrations in Native American Men

Background: Polychlorinated biphenyls (PCBs) and chlorinated pesticides are endocrine disruptors, altering both thyroid and estrogen hormonal systems. Less is known of action on androgenic systems. Objective: We studied the relationship between serum concentrations of testosterone in relation to levels of PCBs and three chlorinated pesticides in an adult Native American (Mohawk) population. Methods: We collected fasting serum samples from 703 adult Mohawks (257 men and 436 women) and analyzed samples for 101 PCB congeners, hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (DDE), and mirex, as well as testosterone, cholesterol, and triglycerides. The associations between testosterone and tertiles of serum organochlorine levels (both wet weight and lipid adjusted) were assessed using a logistic regression model while controlling for age, body mass index (BMI), and other analytes, with the lowest tertile being considered the referent. Males and females were considered separately. Results: Testosterone concentrations in males were inversely correlated with total PCB concentration, whether using wet-weight or lipid-adjusted values. The odds ratio (OR) of having a testosterone concentration above the median was 0.17 [95% confidence interval (CI), 0.05–0.69] for total wet-weight PCBs (highest vs. lowest tertile) after adjustment for age, BMI, total serum lipids, and three pesticides. The OR for lipid-adjusted total PCB concentration was 0.23 (95% CI, 0.06–0.78) after adjustment for other analytes. Testosterone levels were significantly and inversely related to concentrations of PCBs 74, 99, 153, and 206, but not PCBs 52, 105, 118, 138, 170, 180, 201, or 203. Testosterone concentrations in females are much lower than in males, and not significantly related to serum PCBs. HCB, DDE, and mirex were not associated with testosterone concentration in either men or women. Conclusions: Elevation in serum PCB levels is associated with a lower concentration of serum testosterone in Native American men

Identification of the crossing point at N=21 between normal and intruder configurations

The beta(-) decay of Mg-34 was used to study the Al-34 nucleus through. spectroscopy at the Isotope Separator On-Line facility of CERN. Previous studies identified two beta-decaying states in Al-34 having spin-parity assignments J(pi) = 4(-) dominated by the normal configuration pi(d(5/2))(-1)circle times nu(f(7/2)) and J(pi) = 1(+) by the intruder configuration pi(d(5/2))(-1) circle times nu(d(3/2))(-1) (f(7/2))(2). Their unknown ordering and relative energy have been the subject of debate for the placement of Al-34 inside or outside the N = 20 "island of inversion." We report here that the 1(+) intruder lies only 46.6 keV above the 4(-) ground state. In addition, a new half-life of T-1/2 = 44.9(4) ms, that is twice as long as the previously measured 20(10) ms, has been determined for Mg-34. Large-scale shell-model calculations with the recently developed SDPF-U-MIX interaction are compared with the new data and used to interpret the mechanisms at play at the very border of the N = 20 island of inversion.Peer reviewe

The peroxisome proliferator-activated receptor gamma (PPARγ) agonist, rosiglitazone, ameliorates neurofunctional and neuroinflammatory abnormalities in a rat model of Gulf War Illness.

BackgroundGulf War (GW) Illness (GWI) is a debilitating condition with a complex constellation of immune, endocrine and neurological symptoms, including cognitive impairment, anxiety and depression. We studied a novel model of GWI based on 3 known common GW exposures (GWE): (i) intranasal lipopolysaccharide, to which personnel were exposed during desert sand storms; (ii) pyridostigmine bromide, used as prophylaxis against chemical warfare; and (iii) chronic unpredictable stress, an inescapable element of war. We used this model to evaluate prophylactic treatment with the PPARγ agonist, rosiglitazone (ROSI).MethodsRats were subjected to the three GWE for 33 days. In series 1 and 2, male and female GWE-rats were compared to naïve rats. In series 3, male rats with GWE were randomly assigned to prophylactic treatment with ROSI (GWE-ROSI) or vehicle. After the 33-day exposures, three neurofunctional domains were evaluated: cognition (novel object recognition), anxiety-like behaviors (elevated plus maze, open field) and depression-like behaviors (coat state, sucrose preference, splash test, tail suspension and forced swim). Brains were analyzed for astrocytic and microglial activation and neuroinflammation (GFAP, Iba1, tumor necrosis factor and translocator protein). Neurofunctional data from rats with similar exposures were pooled into 3 groups: naïve, GWE and GWE-ROSI.ResultsCompared to naïve rats, GWE-rats showed significant abnormalities in the three neurofunctional domains, along with significant neuroinflammation in amygdala and hippocampus. There were no differences between males and females with GWE. GWE-ROSI rats showed significant attenuation of neuroinflammation and of some of the neurofunctional abnormalities.ConclusionThis novel GWI model recapitulates critical neurofunctional abnormalities reported by Veterans with GWI. Concurrent prophylactic treatment with ROSI was beneficial in this model

Description and assessment of a neurosurgery shadowing and research program: A paradigm for early and sustained exposure to academic neurosurgery

To describe and assess the educational value of a functional neurosurgery clinical shadowing and research tutorial for pre-medical trainees

A Health Literacy-Focused Intervention for Latinos with Hypertension

Latinos in the United States are experiencing increasing incidences of uncontrolled high blood pressure (HBP). Health literacy is an important determinant of adequate HBP self-management, yet no community-based intervention has effectively addressed health literacy in the management of HBP in the target community. The purpose of this study was to test the acceptability and preliminary efficacy of a health literacy-focused HBP intervention in Spanish-speaking Latinos with uncontrolled HBP. Using a one-group pre- and post-test study design, the study intervention was delivered to Spanish-speaking Latinos in Baltimore, MD, who had uncontrolled HBP. The intervention consisted of four weekly group sessions for health literacy training combined with disease knowledge education in HBP management, followed by phone counseling and text messages for 3 months. Seventeen participants received the study intervention. Eleven who completed the follow-up assessment at 16 weeks reported high satisfaction with the intervention. Participation in the intervention resulted in improved blood pressure, numeracy, and psychological outcomes. Our findings support health literacy education as a promising avenue in promoting HBP control among inner-city Spanish-speaking Latinos. [HLRP: Health Literacy Research and Practice. 2018;2(1):e21-e25.]

Molecular biomarker-defined brain tumors: Epidemiology, validity, and completeness in the United States.

BACKGROUND: Selected molecular biomarkers were incorporated into the US cancer registry reporting for patients with brain tumors beginning in 2018. We investigated the completeness and validity of these variables and described the epidemiology of molecularly defined brain tumor types. METHODS: Brain tumor patients with histopathologically confirmed diagnosis in 2018 were identified within the Central Brain Tumor Registry of the United States and NCIs Surveillance, Epidemiology, and End Results Incidence databases. The brain molecular markers (BMM) site-specific data item was assessed for coding completeness and validity. 1p/19q status, MGMT promoter methylation, WHO grade data items, and new ICD-O-3 codes were additionally evaluated. These data were used to profile the characteristics and age-adjusted incidence rates per 100 000 population of molecularly defined brain tumors with 95% confidence intervals (95% CI). RESULTS: BMM completeness across the applicable tumor types was 75%-92% and demonstrated favorable coding validity. IDH-wildtype glioblastomas incidence rate was 1.74 (95% CI: 1.69-1.78), as compared to 0.14 for WHO grade 2 (95% CI: 0.12-0.15), 0.15 for grade 3 (95% CI: 0.14-0.16), and 0.07 for grade 4 (95% CI: 0.06-0.08) IDH-mutant astrocytomas. Irrespective of WHO grade, IDH mutation prevalence was highest in adolescent and young adult patients, and IDH-mutant astrocytomas were more frequently MGMT promoter methylated. Among pediatric-type tumors, the incidence rate was 0.06 for H3K27M-mutant diffuse midline gliomas (95% CI: 0.05-0.07), 0.03 for SHH-activated/TP53-wildtype medulloblastomas (95% CI: 0.02-0.03), and <0.01 for both C19MC-altered embryonal tumor with multilayered rosettes and RELA-fusion ependymomas. CONCLUSIONS: Our findings illustrate the success of developing a dedicated, integrated diagnosis variable, which provides critical molecular information about brain tumors related to accurate diagnosis

Cation flux through SUR1-TRPM4 and NCX1 in astrocyte endfeet induces water influx through AQP4 and brain swelling after ischemic stroke

Brain swelling causes morbidity and mortality in various brain injuries and diseases but lacks effective treatments. Brain swelling is linked to the influx of water into perivascular astrocytes through channels called aquaporins. Water accumulation in astrocytes increases their volume, which contributes to brain swelling. Using a mouse model of severe ischemic stroke, we identified a potentially targetable mechanism that promoted the cell surface localization of aquaporin 4 (AQP4) in perivascular astrocytic endfeet, which completely ensheathe the brain\u27s capillaries. Cerebral ischemia increased the abundance of the heteromeric cation channel SUR1-TRPM4 and of the Na/Ca exchanger NCX1 in the endfeet of perivascular astrocytes. The influx of Na through SUR1-TRPM4 induced Ca transport into cells through NCX1 operating in reverse mode, thus raising the intra-endfoot concentration of Ca. This increase in Ca stimulated calmodulin-dependent translocation of AQP4 to the plasma membrane and water influx, which led to cellular edema and brain swelling. Pharmacological inhibition or astrocyte-specific deletion of SUR1-TRPM4 or NCX1 reduced brain swelling and improved neurological function in mice to a similar extent as an AQP4 inhibitor and was independent of infarct size. Thus, channels in astrocyte endfeet could be targeted to reduce postischemic brain swelling in stroke patients