Developing Health-Based Pre-Planning Clearance Goals for Airport Remediation Following a Chemical Terrorist Attack: Decision Criteria for Multipathway Exposure Routes

In the event of a chemical terrorist attack on a transportation hub, post-event remediation and restoration activities necessary to attain unrestricted facility re-use and re-entry could require hours to multiple days. While timeframes are dependent on numerous variables, a primary controlling factor is the level of pre-planning and decision-making completed prior to chemical release. What follows is the second of a two-part analysis identifying key considerations, critical information and decision criteria to facilitate post-attack and post-decontamination consequence management activities. Decision criteria analysis presented here provides first-time, open-literature documentation of multi-pathway, health-based remediation exposure guidelines for selected toxic industrial compounds, chemical warfare agents, and agent degradation products for pre-planning application in anticipation of a chemical terrorist attack. Guideline values are provided for inhalation and direct ocular vapor exposure routes as well as percutaneous vapor, surface contact, and ingestion. Target populations include various employees as well as transit passengers. This work has been performed as a national case study conducted in partnership with the Los Angeles International Airport and The Bradley International Terminal. All recommended guidelines have been selected for consistency with airport scenario release parameters of a one-time, short-duration, finite airborne release from a single source followed by compound-specific decontamination

Healthcare workers as parents: attitudes toward vaccinating their children against pandemic influenza A/H1N1

<p>Abstract</p> <p>Background</p> <p>Both the health care workers (HCWs) and children are target groups for pandemic influenza vaccination. The coverage of the target populations is an important determinant for impact of mass vaccination. The objective of this study is to determine the attitudes of HCWs as parents, toward vaccinating their children with pandemic influenza A/H1N1 vaccine.</p> <p>Methods</p> <p>A cross-sectional questionnaire survey was conducted with health care workers (HCWs) in a public hospital during December 2009 in Istanbul. All persons employed in the hospital with or without a health-care occupation are accepted as HCW. The HCWs who are parents of children 6 months to 18 years of age were included in the study. Pearson's chi-square test and logistic regression analysis was applied for the statistical analyses.</p> <p>Results</p> <p>A total of 389 HCWs who were parents of children aged 6 months-18 years participated study. Among all participants 27.0% (n = 105) reported that themselves had been vaccinated against pandemic influenza A/H1N1. Two third (66.1%) of the parents answered that they will not vaccinate their children, 21.1% already vaccinated and 12.9% were still undecided. Concern about side effect was most reported reason among who had been not vaccinated their children and among undecided parents. The second reason for refusing the pandemic vaccine was concerns efficacy of the vaccine. Media was the only source of information about pandemic influenza in nearly one third of HCWs. Agreement with vaccine safety, self receipt of pandemic influenza A/H1N1 vaccine, and trust in Ministry of Health were found to be associated with the positive attitude toward vaccinating their children against pandemic influenza A/H1N1.</p> <p>Conclusions</p> <p>Persuading parents to accept a new vaccine seems not be easy even if they are HCWs. In order to overcome the barriers among HCWs related to pandemic vaccines, determination of their misinformation, attitudes and behaviors regarding the pandemic influenza vaccination is necessary. Efforts for orienting the HCWs to use evidence based scientific sources, rather than the media for information should be considered by the authorities.</p

Recent breast cancer trends among Asian/Pacific Islander, Hispanic, and African-American women in the US: changes by tumor subtype

Abstract available at publisher's website

Higher incidence of premenopausal breast cancer in less developed countries; myth or truth?

Background: Fundamental etiologic differences have been suggested to cause earlier onset of breast cancer in less developed countries (LDCs) than in more developed countries (MDCs). We explored this hypothesis using world-wide breast cancer incidence data. Methods: We compared international age-standardized incidence rates (ASR) of pre- (<50 years) and postmenopausal (≥50 years) breast cancers as well as temporal trends in ASRs of pre-and postmenopausal breast cancer among selected countries during 1975–2008. We used joinpoint log-linear regression analysis to estimate annual percent changes (APC) for premenopausal and postmenopausal breast cancer in the northern Europe and in Black and White women population in the US. Results: Premenopausal breast cancers comprised a substantially higher proportion of all incident breast cancers in LDCs (average 47.3%) compared to MDCs (average 18.5%). However, the ASR of premenopausal breast cancer was consistently higher in MDCs (29.4/100,000) than LDCs (12.8/100,000). The ASR of postmenopausal cancer was about five-fold higher in the MDCs (307.6/100,000) than the LDCs (65.4/100,000). The APC of breast cancer in Denmark was substantially higher in postmenopausal (1.33%) than premenopausal cancer (0.98%). Higher incidence of breast cancer among the white than black women in the US was pertained only to the postmenopausal cancer. Conclusion: The substantial and consistent lower age-specific incidence of breast cancer in LDCs than in MDCs contradicts the theory of earlier onset. Demographic differences with fewer old women in LDCs and lower prevalence of risk factors of postmenopausal cancer are the most likely explanation to the lower mean age at diagnosis in these countries

Social participation reduces depressive symptoms among older adults: An 18-year longitudinal analysis in Taiwan

<p>Abstract</p> <p>Background</p> <p>Relatively little empirical attention has focused on the association between social participation and depressive symptoms amongst older adults in Asian nations, where persons over the age of 65 represent a rapidly growing segment of the population. This study explores the dynamic relationship between participation in social activities and trajectories of depressive symptomatology among older Taiwanese adults surveyed over 18 years.</p> <p>Methods</p> <p>Data are from a nationally representative sample of 1,388 adults aged 60-64 first surveyed in 1989 and followed over an 18-year time period for a total of six waves. Individual involvement in social activities was categorized into continuous participation, ceased participation before age 70, initiating participation in older adulthood, never participated, and dropped out before age 70. Two domains of depressive symptoms--negative affect and lack of positive affect--were measured using a 10-item version of the Center for Epidemiologic Studies-Depression Scale.</p> <p>Results</p> <p>Analyses using growth curve modeling showed that continuously participating or initiating participation in social activities later life is significantly associated with fewer depressive symptoms among older Taiwanese adults, even after controlling for the confounding effects of aging, individual demographic differences, and health status.</p> <p>Conclusions</p> <p>These findings suggest that maintaining or initiating social participation in later life benefits the mental health of older adults. Facilitating social activities among older adults is a promising direction for programs intended to promote mental health and successful aging among older adults in Taiwan.</p

Maternal Use of Antibiotics, Hospitalisation for Infection during Pregnancy, and Risk of Childhood Epilepsy: A Population-Based Cohort Study

BACKGROUND: Maternal infection during pregnancy may be a risk factor for epilepsy in offspring. Use of antibiotics is a valid marker of infection. METHODOLOGY/PRINCIPAL FINDINGS: To examine the relationship between maternal infection during pregnancy and risk of childhood epilepsy we conducted a historical cohort study of singletons born in northern Denmark from 1998 through 2008 who survived ≥29 days. We used population-based medical databases to ascertain maternal use of antibiotics or hospital contacts with infection during pregnancy, as well as first-time hospital contacts with a diagnosis of epilepsy among offspring. We compared incidence rates (IR) of epilepsy among children of mothers with and without infection during pregnancy. We examined the outcome according to trimester of exposure, type of antibiotic, and total number of prescriptions, using Poisson regression to estimate incidence rate ratios (IRRs) while adjusting for covariates. Among 191,383 children in the cohort, 948 (0.5%) were hospitalised or had an outpatient visit for epilepsy during follow-up, yielding an IR of 91 per 100 000 person-years (PY). The five-year cumulative incidence of epilepsy was 4.5 per 1000 children. Among children exposed prenatally to maternal infection, the IR was 117 per 100,000 PY, with an adjusted IRR of 1.40 (95% confidence interval (CI): 1.22-1.61), compared with unexposed children. The association was unaffected by trimester of exposure, antibiotic type, or prescription count. CONCLUSIONS/SIGNIFICANCE: Prenatal exposure to maternal infection is associated with an increased risk of epilepsy in childhood. The similarity of estimates across types of antibiotics suggests that processes common to all infections underlie this outcome, rather than specific pathogens or drugs

A VLP-based vaccine targeting domain III of the West Nile virus E protein protects from lethal infection in mice

Background. Since its first appearance in the USA in 1999, West Nile virus (WNV) has spread in the Western hemisphere and continues to represent an important public health concern. In the absence of effective treatment, there is a medical need for the development of a safe and efficient vaccine. Live attenuated WNV vaccines have shown promise in preclinical and clinical studies but might carry inherent risks due to the possibility of reversion to more virulent forms. Subunit vaccines based on the large envelope (E) glycoprotein of WNV have therefore been explored as an alternative approach. Although these vaccines were shown to protect from disease in animal models, multiple injections and/or strong adjuvants were required to reach efficacy, underscoring the need for more immunogenic, yet safe DIII-based vaccines. Results. We produced a conjugate vaccine against WNV consisting of recombinantly expressed domain III (DIII) of the E glycoprotein chemically cross-linked to virus-like particles derived from the recently discovered bacteriophage AP205. In contrast to isolated DIII protein, which required three administrations to induce detectable antibody titers in mice, high titers of DIII-specific antibodies were induced after a single injection of the conjugate vaccine. These antibodies were able to neutralize the virus in vitro and provided partial protection from a challenge with a lethal dose of WNV. Three injections of the vaccine induced high titers of virus-neutralizing antibodies, and completely protected mice from WNV infection. Conclusions. The immunogenicity of DIII can be strongly enhanced by conjugation to virus-like particles of the bacteriophage AP205. The superior immunogenicity of the conjugate vaccine with respect to other DIII-based subunit vaccines, its anticipated favourable safety profile and low production costs highlight its potential as an efficacious and cost-effective prophylaxis against WNV

Control of Bone Mass and Remodeling by PTH Receptor Signaling in Osteocytes

Osteocytes, former osteoblasts buried within bone, are thought to orchestrate skeletal adaptation to mechanical stimuli. However, it remains unknown whether hormones control skeletal homeostasis through actions on osteocytes. Parathyroid hormone (PTH) stimulates bone remodeling and may cause bone loss or bone gain depending on the balance between bone resorption and formation. Herein, we demonstrate that transgenic mice expressing a constitutively active PTH receptor exclusively in osteocytes exhibit increased bone mass and bone remodeling, as well as reduced expression of the osteocyte-derived Wnt antagonist sclerostin, increased Wnt signaling, increased osteoclast and osteoblast number, and decreased osteoblast apoptosis. Deletion of the Wnt co-receptor LDL related receptor 5 (LRP5) attenuates the high bone mass phenotype but not the increase in bone remodeling induced by the transgene. These findings demonstrate that PTH receptor signaling in osteocytes increases bone mass and the rate of bone remodeling through LRP5-dependent and -independent mechanisms, respectively

Mu-Opioid Receptors Transiently Activate the Akt-nNOS Pathway to Produce Sustained Potentiation of PKC-Mediated NMDAR-CaMKII Signaling

BACKGROUND: In periaqueductal grey (PAG) matter, cross-talk between the Mu-opioid receptor (MOR) and the glutamate N-methyl-D-Aspartate receptor (NMDAR)-CaMKII pathway supports the development of analgesic tolerance to morphine. In neurons, histidine triad nucleotide binding protein 1 (HINT1) connects the regulators of G protein signaling RGSZ1 and RGSZ2 to the C terminus of the MOR. In response to morphine, this HINT1-RGSZ complex binds PKCgamma, and afterwards, the interplay between PKCgamma, Src and Gz/Gi proteins leads to sustained potentiation of NMDAR-mediated glutamate responses. METHODOLOGY/PRINCIPAL FINDINGS: Following an intracerebroventricular (icv) injection of 10 nmol morphine, Akt was recruited to the synaptosomal membrane and activated by Thr308 and Ser473 phosphorylation. The Akt activation was immediately transferred to neural Nitric Oxide Synthase (nNOS) Ser1417. Afterwards, nitric oxide (NO)-released zinc ions recruited PKCgamma to the MOR to promote the Src-mediated phosphorylation of the Tyr1325 NMDAR2A subunit. This action increased NMDAR calcium flux and CaMKII was activated in a calcium-calmodulin dependent manner. CaMKII then acted on nNOS Ser847 to produce a sustained reduction in NO levels. The activation of the Akt-nNOS pathway was also reduced by the binding of these proteins to the MOR-HINT1 complex where they remained inactive. Tolerance to acute morphine developed as a result of phosphorylation of MOR cytosolic residues, uncoupling from the regulated G proteins which are transferred to RGSZ2 proteins. The diminished effect of morphine was prevented by LNNA, an inhibitor of nNOS function, and naltrindole, a delta-opioid receptor antagonist that also inhibits Akt. CONCLUSIONS/SIGNIFICANCE: Analysis of the regulatory phosphorylation of the proteins included in the study indicated that morphine produces a transient activation of the Akt/PKB-nNOS pathway. This activation occurs upstream of PKCgamma and Src mediated potentiation of NMDAR activity, ultimately leading to morphine tolerance. In summary, the Akt-nNOS pathway acts as a primer for morphine-triggered events which leads to the sustained potentiation of the NMDAR-CaMKII pathway and MOR inhibition