Psychological response to disaster: implications for Hawaii.

Given the frequency of natural disasters in Hawaii, it is important for practitioners to be aware of the numerous resulting psychological responses and risk factors, especially those unique to Hawaii. Practical guidelines are presented for practitioners, both in providing leadership during the disaster and in screening for psychopathology thereafter

Mechanisms of Inhaled Fine Particulate Air Pollution–Induced Arterial Blood Pressure Changes

Background: Epidemiologic studies suggest a positive association between fine particulate matter and arterial blood pressure, but the results have been inconsistent. Objectives: We investigated the effect of ambient particles on systemic hemodynamics during a 5-hr exposure to concentrated ambient air particles (CAPs) or filtered air (FA) in conscious canines. Methods: Thirteen dogs were repeatedly exposed via permanent tracheostomy to CAPs (358.1 ± 306.7 μg/m$^3$, mean ± SD) or FA in a crossover protocol (55 CAPs days, 63 FA days). Femoral artery blood pressure was monitored continuously via implanted telemetry devices. We measured baroreceptor reflex sensitivity before and after exposure in a subset of these experiments (n = 10 dogs, 19 CAPs days, 20 FA days). In additional experiments, we administered α-adrenergic blockade before exposure (n = 8 dogs, 16 CAPs days, 15 FA days). Blood pressure, heart rate, rate–pressure product, and baroreceptor reflex sensitivity responses were compared using linear mixed-effects models. Results: CAPs exposure increased systolic blood pressure (2.7 ± 1.0 mmHg, p = 0.006), diastolic blood pressure (4.1 ± 0.8 mmHg; p < 0.001), mean arterial pressure (3.7 ± 0.8 mmHg; p < 0.001), heart rate (1.6 ± 0.5 bpm; p < 0.001), and rate–pressure product (539 ± 110 bpm × mmHg; p < 0.001), and decreased pulse pressure (−1.7 ± 0.7 mmHg, p = 0.02). These changes were accompanied by a 20 ± 6 msec/mmHg (p = 0.005) increase in baroreceptor reflex sensitivity after CAPs versus FA. After α-adrenergic blockade, responses to CAPs and FA no longer differed significantly. Conclusions: Controlled exposure to ambient particles elevates arterial blood pressure. Increased peripheral vascular resistance may mediate these changes, whereas increased baroreceptor reflex sensitivity may compensate for particle-induced alterations in blood pressure

Dual Use of a Patient Portal and Clinical Video Telehealth by Veterans with Mental Health Diagnoses: Retrospective, Cross-Sectional Analysis

BACKGROUND: Access to mental health care is challenging. The Veterans Health Administration (VHA) has been addressing these challenges through technological innovations including the implementation of Clinical Video Telehealth, two-way interactive and synchronous videoconferencing between a provider and a patient, and an electronic patient portal and personal health record, My HealtheVet. OBJECTIVE: This study aimed to describe early adoption and use of My HealtheVet and Clinical Video Telehealth among VHA users with mental health diagnoses. METHODS: We conducted a retrospective, cross-sectional analysis of early My HealtheVet adoption and Clinical Video Telehealth engagement among veterans with one or more mental health diagnoses who were VHA users from 2007 to 2012. We categorized veterans into four electronic health (eHealth) technology use groups: My HealtheVet only, Clinical Video Telehealth only, dual users who used both, and nonusers of either. We examined demographic characteristics and mental health diagnoses by group. We explored My HealtheVet feature use among My HealtheVet adopters. We then explored predictors of My HealtheVet adoption, Clinical Video Telehealth engagement, and dual use using multivariate logistic regression. RESULTS: Among 2.17 million veterans with one or more mental health diagnoses, 1.51% (32,723/2,171,325) were dual users, and 71.72% (1,557,218/2,171,325) were nonusers of both My HealtheVet and Clinical Video Telehealth. African American and Latino patients were significantly less likely to engage in Clinical Video Telehealth or use My HealtheVet compared with white patients. Low-income patients who met the criteria for free care were significantly less likely to be My HealtheVet or dual users than those who did not. The odds of Clinical Video Telehealth engagement and dual use decreased with increasing age. Women were more likely than men to be My HealtheVet or dual users but less likely than men to be Clinical Video Telehealth users. Patients with schizophrenia or schizoaffective disorder were significantly less likely to be My HealtheVet or dual users than those with other mental health diagnoses (odds ratio, OR 0.50, CI 0.47-0.53 and OR 0.75, CI 0.69-0.80, respectively). Dual users were younger (53.08 years, SD 13.7, vs 60.11 years, SD 15.83), more likely to be white, and less likely to be low-income than the overall cohort. Although rural patients had 17% lower odds of My HealtheVet adoption compared with urban patients (OR 0.83, 95% CI 0.80-0.87), they were substantially more likely than their urban counterparts to engage in Clinical Video Telehealth and dual use (OR 2.45, 95% CI 1.95-3.09 for Clinical Video Telehealth and OR 2.11, 95% CI 1.81-2.47 for dual use). CONCLUSIONS: During this study (2007-2012), use of these technologies was low, leaving much potential for growth. There were sociodemographic disparities in access to My HealtheVet and Clinical Video Telehealth and in dual use of these technologies. There was also variation based on types of mental health diagnosis. More research is needed to ensure that these and other patient-facing eHealth technologies are accessible and effectively used by all vulnerable patients

TRPA1 and Sympathetic Activation Contribute to Increased Risk of Triggered Cardiac Arrhythmias in Hypertensive Rats Exposed to Diesel Exhaust

Background: Diesel exhaust (DE), which is emitted from on- and off-road sources, is a complex mixture of toxic gaseous and particulate components that leads to triggered adverse cardiovascular effects such as arrhythmias

Ambient Fine Particulate Matter Exposure and Myocardial Ischemia in the Environmental Epidemiology of Arrhythmogenesis in the Women’s Health Initiative (EEAWHI) Study

BackgroundAmbient particulate matter (PM) air pollution is associated with coronary heart disease, but the pathways underlying the association remain to be elucidated.MethodsWe studied the association between PM and ischemia among 57,908 Women’s Health Initiative clinical trial participants from 1999–2003. We used the Minnesota Code criteria to identify ST-segment and T-wave abnormalities, and estimated T amplitude (microvolt) from resting, standard 12-lead electrocardiogram (ECG). We used U.S. Environmental Protection Agency’s monitor data to estimate concentrations of PM < 2.5 μm (PM2.5) at geocoded participant addresses over 6 days before the ECGs (lag0 through lag5). We excluded 2,379 women with ECG QRS duration ≥ 120 msec.ResultsOverall, 6% of the remaining 55,529 women (52–90 years of age; 83% non-Hispanic white) had ST abnormalities and 16% had T abnormalities. Lead-specific T amplitude was normally distributed (range of means from −14 to 349 μV). PM2.5 (mean ± SD) averaged over lag0–2 was 14 ± 7 μg/m3. In logistic and linear regression models adjusted for demographic, clinical, temporal, and climatic factors, a 10-μg/m3 increase in lag0–2 PM2.5 was associated with a 4% [95% confidence interval (CI), −3%, to 10%] increase in the odds of ST abnormality and a 5% (95% CI, 0% to 9%) increase in the odds of T abnormality. We observed corresponding decreases in T amplitude in all exam sites and leads except lead V1, reaching a minimum of −2 μV (95% CI, −5 to 0 μV) in lead V3.ConclusionsShort-term PM2.5 exposure is associated with ECG evidence of myocardial ischemia among postmenopausal women. The principal manifestations include subclinical but potentially arrhythmogenic ST–T abnormalities and decreases in T amplitude

Asbestos Burden Predicts Survival in Pleural Mesothelioma

Background: Malignant pleural mesothelioma (MPM) is a rapidly fatal asbestos-associated malignancy with a median survival time of &lt; 1 year following diagnosis. Treatment strategy is determined in part using known prognostic factors. Objective: The aim of this study was to examine the relationship between asbestos exposure and survival outcome in MPM in an effort to advance the understanding of the contribution of asbestos exposure to MPM prognosis. Methods: We studied incident cases of MPM patients enrolled through the International Mesothelioma Program at Brigham and Women’s Hospital in Boston, Massachusetts, using survival follow-up, self-reported asbestos exposure (n = 128), and a subset of cases (n = 80) with quantitative asbestos fiber burden measures. Results: Consistent with the established literature, we found independent, significant associations between male sex and reduced survival (p 1,099), suggested a survival duration association among these groups (p = 0.06). After adjusting for covariates in a Cox model, we found that patients with a low asbestos burden had a 3-fold elevated risk of death compared to patients with a moderate fiber burden [95% confidence interval (CI), 0.95–9.5; p = 0.06], and patients with a high asbestos burden had a 4.8-fold elevated risk of death (95% CI, 1.5–15.0; p < 0.01) versus those with moderate exposure. Conclusion: Our data suggest that patient survival is associated with asbestos fiber burden in MPM and is perhaps modified by susceptibility

The Role of Particulate Matter-Associated Zinc in Cardiac Injury in Rats

Background: Exposure to particulate matter (PM) has been associated with increased cardiovascular morbidity; however, causative components are unknown. Zinc is a major element detected at high levels in urban air.Objective We investigated the role of PM-associated zinc in cardiac injury. Methods: We repeatedly exposed 12- to 14-week-old male Wistar Kyoto rats intratracheally (1×/week for 8 or16 weeks) to a) saline (control); b) PM having no soluble zinc (Mount St. Helens ash, MSH); or c) whole-combustion PM suspension containing 14.5 μg/mg of water-soluble zinc at high dose (PM-HD) and d ) low dose (PM-LD), e) the aqueous fraction of this suspension (14.5 μg/mg of soluble zinc) (PM-L), or f ) zinc sulfate (rats exposed for 8 weeks received double the concentration of all PM components of rats exposed for 16 weeks). Results: Pulmonary inflammation was apparent in all exposure groups when compared with saline (8 weeks greater than 16 weeks). PM with or without zinc, or with zinc alone caused small increases in focal subepicardial inflammation, degeneration, and fibrosis. Lesions were not detected in controls at 8 weeks but were noted at 16 weeks. We analyzed mitochondrial DNA damage using quantitative polymerase chain reaction and found that all groups except MSH caused varying degrees of damage relative to control. Total cardiac aconitase activity was inhibited in rats receiving soluble zinc. Expression array analysis of heart tissue revealed modest changes in mRNA for genes involved in signaling, ion channels function, oxidative stress, mitochondrial fatty acid metabolism, and cell cycle regulation in zinc but not in MSH-exposed rats. Conclusion: These results suggest that water-soluble PM-associated zinc may be one of the causal components involved in PM cardiac effects

FGFR2 risk SNPs confer breast cancer risk by augmenting oestrogen responsiveness.

The fibroblast growth factor receptor 2 (FGFR2) locus is consistently the top hit in genome-wide association studies for oestrogen receptor-positive (ER(+)) breast cancer. Yet, its mode of action continues to be controversial. Here, we employ a systems biology approach to demonstrate that signalling via FGFR2 counteracts cell activation by oestrogen. In the presence of oestrogen, the oestrogen receptor (ESR1) regulon (set of ESR1 target genes) is in an active state. However, signalling by FGFR2 is able to reverse the activity of the ESR1 regulon. This effect is seen in multiple distinct FGFR2 signalling model systems, across multiple cells lines and is dependent on the presence of FGFR2. Increased oestrogen exposure has long been associated with an increased risk of breast cancer. We therefore hypothesized that risk variants should reduce FGFR2 expression and subsequent signalling. Indeed, transient transfection experiments assaying the three independent variants of the FGFR2 risk locus (rs2981578, rs35054928 and rs45631563) in their normal chromosomal context show that these single-nucleotide polymorphisms (SNPs) map to transcriptional silencer elements and that, compared with wild type, the risk alleles augment silencer activity. The presence of risk variants results in lower FGFR2 expression and increased oestrogen responsiveness. We thus propose a molecular mechanism by which FGFR2 can confer increased breast cancer risk that is consistent with oestrogen exposure as a major driver of breast cancer risk. Our findings may have implications for the clinical use of FGFR2 inhibitors.Breast Cancer Research FoundationThis is the final version of the article. It first appeared from Oxford University Press via https://doi.org/10.1093/carcin/bgw06

Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease

Neuronal ceroid lipofuscinoses (NCLs; Batten disease) are collectively the most frequent autosomal-recessive neurodegenerative disease of childhood, but the underlying cellular and molecular mechanisms remain unclear. Several lines of evidence have highlighted the important role that non-somatic compartments of neurons (axons and synapses) play in the instigation and progression of NCL pathogenesis. Here, we report a progressive breakdown of axons and synapses in the brains of two different mouse models of NCL: Ppt1−/− model of infantile NCL and Cln6nclf model of variant late-infantile NCL. Synaptic pathology was evident in the thalamus and cortex of these mice, but occurred much earlier within the thalamus. Quantitative comparisons of expression levels for a subset of proteins previously implicated in regulation of axonal and synaptic vulnerability revealed changes in proteins involved with synaptic function/stability and cell-cycle regulation in both strains of NCL mice. Protein expression changes were present at pre/early-symptomatic stages, occurring in advance of morphologically detectable synaptic or axonal pathology and again displayed regional selectivity, occurring first within the thalamus and only later in the cortex. Although significant differences in individual protein expression profiles existed between the two NCL models studied, 2 of the 15 proteins examined (VDAC1 and Pttg1) displayed robust and significant changes at pre/early-symptomatic time-points in both models. Our study demonstrates that synapses and axons are important early pathological targets in the NCLs and has identified two proteins, VDAC1 and Pttg1, with the potential for use as in vivo biomarkers of pre/early-symptomatic axonal and synaptic vulnerability in the NCLs