Foot-and-mouth disease virus induces autophagosomes during cell entry via a class III phosphatidylinositol 3-kinase-independent pathway.

Autophagy is an intracellular pathway that can contribute to innate antiviral immunity by delivering viruses to lysosomes for degradation or can be beneficial for viruses by providing specialized membranes for virus replication. Here, we show that the picornavirus foot-and-mouth disease virus (FMDV) induces the formation of autophagosomes. Induction was dependent on Atg5, involved processing of LC3 to LC3II, and led to a redistribution of LC3 from the cytosol to punctate vesicles indicative of authentic autophagosomes.

From DTCA-PD to patient information to health information: the complex politics and semantics of EU health policy.

Rationale, Aims And Objectives: Between 2001 and 2011 the pharmaceutical industry, supported by DG Enterprise, was engaged in an ongoing campaign to repeal/amend the European Union (EU) ban on direct-to-consumer advertising of prescription drugs (DTCA-PD). As it became increasingly clear that the ban would not be repealed, DTCA-PD supporters tried to shift the debate away from advertising and towards the provision of 'patient information' and the rights of patients to access such information. Meanwhile, a variety of national and European health organizations, supported by DG SANCO, sought to maintain the ban and oppose the industry-supported 'patient information' campaign.

Control of vertebrate intraflagellar transport by the planar cell polarity effector Fuz.

Cilia play key roles in development and homeostasis, and defects in cilia structure or function lead to an array of human diseases. Ciliogenesis is accomplished by the intraflagellar transport (IFT) system, a set of proteins governing bidirectional transport of cargoes within ciliary axonemes. In this paper, we present a novel platform for in vivo analysis of vertebrate IFT dynamics.

Personal characteristics affecting veterans' use of services for posttraumatic stress disorder.

Objective: Posttraumatic stress disorder (PTSD) is widespread among veterans, but many veterans with PTSD use few health services. This study examined how individual characteristics influenced use of outpatient visits by veterans with PTSD.

Methods: The study assessed number of annual visits by 414,748 veterans with PTSD who sought care from October 2007 through September 2008 at U.

Comparing substance use monitoring and treatment variations among physician health programs.

There is growing evidence that physician health programs (PHPs) are an important component in physicians' recovery from substance disorders, although we do not know how variations in treatment and monitoring affect physician recovery. This study was designed to understand how programmatic differences impact clients' overall program completion. This study was part of a larger investigation, the Blueprint Project, which evaluated outcomes for clients enrolled in PHPs nationally.

Quality and safety of integrated community case management of malaria using rapid diagnostic tests and pneumonia by community health workers.

Objectives: To assess the quality and safety of having community health workers (CHWs) in rural Zambia use rapid diagnostic tests (RDTs) and provide integrated management of malaria and pneumonia.

Design/methods: In the context of a cluster-randomized controlled trial of two models for community-based management of malaria and/or non-severe pneumonia in children under 5 years old, CHWs in the intervention arm were trained to use RDTs, follow a simple algorithm for classification and treat malaria with artemether-lumefantrine (AL) and pneumonia with amoxicillin. CHW records were reviewed to assess the ability of the CHWs to appropriately classify and treat malaria and pneumonia, and account for supplies.

2009 H1N1 fatalities: the New Mexico experience.

Histopathologic features of New Mexico 2009 H1N1 fatalities have not been representative of those reported nationwide. We retrospectively reviewed medical records of all New Mexico 2009 pandemic influenza A (pH1N1) fatalities (n = 50). In cases in which autopsy was performed (n = 12), histologic sections and culture results were examined.

Discovery of a novel series of potent and orally bioavailable phosphoinositide 3-kinase γ inhibitors.

The phosphoinositide 3-kinases (PI3Ks) have been linked to an extraordinarily diversified group of cellular functions making these enzymes compelling targets for the treatment of disease. A large body of evidence has linked PI3Kγ to the modulation of autoimmune and inflammatory processes making it an intriguing target for drug discovery. Our high-throughput screening (HTS) campaign revealed two hits that were nominated for further optimization studies.

Mouse model for efficacy testing of antituberculosis agents via intrapulmonary delivery.

Here we describe an experimental murine model that allows for aerosolized antituberculosis drug efficacy testing. Intrapulmonary aerosol delivery of isoniazid, capreomycin, and amikacin to mice with pulmonary infection of Mycobacterium tuberculosis demonstrated efficacy in reducing pulmonary bacterial loads similar to that seen by standard drug delivery methods, even when lower concentrations of drugs and fewer doses were used in the aerosolized drug regimens. Interestingly, intrapulmonary delivery of isoniazid also reduced the bacterial load in the spleen.

The health implications of civic association in Russia.

Can civic and political participation influence health outcomes, and if so, does the general aversion to joining community activities have some connection to poor health outcomes in Russia? Using data from surveys of 18,000+ urban Russians conducted from 2003 to 2005 and controlling for a wide range of variables, we find that individuals who join collective civic and political activities report better health than non-joiners and that living in a participatory community may enhance one's health, regardless of one's own participation.

Physician boundary violations in a physician's health program: a 19-year review.

Managing and treating physicians with professional boundary violations is of paramount importance with vast implications for public safety. Physician Health Programs (PHPs) evaluate and monitor many, if not most, physicians receiving care for these abuses. We conducted a chart review of 120 physicians monitored for boundary violations.

Self-prescribed and other informal care provided by physicians: scope, correlations and implications.

Background: While it is generally acknowledged that self-prescribing among physicians poses some risk, research finds such behaviour to be common and in certain cases accepted by the medical community. Largely absent from the literature is knowledge about other activities doctors perform for their own medical care or for the informal treatment of family and friends. This study examined the variety, frequency and association of behaviours doctors report providing informally.

Disease-associated polyglutamine stretches in monomeric huntingtin adopt a compact structure.

Abnormal polyglutamine (polyQ) tracts are the only common feature in nine proteins that each cause a dominant neurodegenerative disorder. In Huntington's disease, tracts longer than 36 glutamines in the protein huntingtin (htt) cause degeneration. In situ, monoclonal antibody 3B5H10 binds to different htt fragments in neurons in proportion to their toxicity.

Characteristics of telemental health service use by American Indian veterans.

Objective: This study examined use by American Indian and Alaska Native veterans of services provided by specialty telemental health clinics focused on posttraumatic stress disorder. These clinics offer services via videoconferencing to address challenges faced by rural veterans in accessing care.

Methods: A retrospective chart and electronic medical record review was conducted for 85 male veterans who used services at two rural telemental health clinics from 2001 through 2006.

Review of American Indian veteran telemental health.

Rural American Indian veterans have unique healthcare needs and face numerous barriers to accessing healthcare services. Over the past decade, the Department of Veterans Affairs in conjunction with the University of Colorado Denver has turned to the promising field of telemental health to develop a series of videoconferencing-based clinics to reach this vulnerable population and improve mental healthcare services. The ongoing development, implementation, and expansion of these clinics have been assessed as part of a program improvement.

Mycoplasma pneumoniae CARDS toxin induces pulmonary eosinophilic and lymphocytic inflammation.

Mycoplasma pneumoniae causes acute and chronic lung infections in humans, leading to a variety of pulmonary and extrapulmonary sequelae. Of the airway complications of M. pneumoniae infection, M.

Activation of colonic mucosal 5-HT(4) receptors accelerates propulsive motility and inhibits visceral hypersensitivity.

Background & Aims: 5-hydroxytryptamine receptor (5-HT(4)R) agonists promote gastrointestinal motility and attenuate visceral pain, but concerns about adverse reactions have restricted their availability. We tested the hypotheses that 5-HT(4) receptors are expressed in the colonic epithelium and that 5-HT(4)R agonists can act intraluminally to increase motility and reduce visceral hypersensitivity.

Methods: Mucosal expression of the 5-HT(4)R was evaluated by reverse-transcriptase polymerase chain reaction and immunohistochemical analysis of tissues from 5-HT(4)R(BAC)-enhanced green fluorescent protein mice.

Crossing borders: a critical review of the role of the European Court of Justice in EU health policy.

Over the last two decades, the European Union (EU) has steadily increased its involvement in the health policies of its member states, with considerable support from the European Court of Justice (ECJ). However, much of the literature examining the Court's role has focused upon the intersection between internal market law and the health services sector; the majority of studies have failed to examine the potential role for the Court in public health policy. Observers such as Greer have seen the development of healthcare as a clear case of neofunctional spillover, a view supported but qualified by Wasserfallen and others, who present a more detailed account of the mechanics of the process.

Clustering-Based Method for Developing a Genomic Copy Number Alteration Signature for Predicting the Metastatic Potential of Prostate Cancer.

The transition of cancer from a localized tumor to a distant metastasis is not well understood for prostate and many other cancers, partly, because of the scarcity of tumor samples, especially metastases, from cancer patients with long-term clinical follow-up. To overcome this limitation, we developed a semi-supervised clustering method using the tumor genomic DNA copy number alterations to classify each patient into inferred clinical outcome groups of metastatic potential. Our data set was comprised of 294 primary tumors and 49 metastases from 5 independent cohorts of prostate cancer patients.

A physiologically based pharmacokinetic model for capreomycin.

The emergence of multidrug-resistant tuberculosis (MDR-TB) has led to a renewed interest in the use of second-line antibiotic agents. Unfortunately, there are currently dearths of information, data, and computational models that can be used to help design rational regimens for administration of these drugs. To help fill this knowledge gap, an exploratory physiologically based pharmacokinetic (PBPK) model, supported by targeted experimental data, was developed to predict the absorption, distribution, metabolism, and excretion (ADME) of the second-line agent capreomycin, a cyclic peptide antibiotic often grouped with the aminoglycoside antibiotics.

The diffusion of telehealth in rural American Indian communities: a retrospective survey of key stakeholders.

Objective: Mental health issues are a serious concern for many American Indian Veterans, especially for post-traumatic stress disorder and related psychiatric conditions. Yet, acquiring mental health treatment can be a challenge in Native communities where specialized services are largely unavailable. Consequently, telehealth is increasingly being suggested as a way to expand healthcare access on or near reservation lands.

In situ hybridization signal patterns in recurrent laryngeal squamous papillomas indicate that HPV integration occurs at an early stage.

Laryngeal papillomas are benign tumors that frequently recur and can compromise airways. We investigated HPV genotype, physical status, and protein expression in juveniles versus adults. Thirty-five laryngeal papilloma specimens were obtained from ten juveniles (1-16 years) and eleven adults (24-67 years).

Identifying polyglutamine protein species in situ that best predict neurodegeneration.

Polyglutamine (polyQ) stretches exceeding a threshold length confer a toxic function to proteins that contain them and cause at least nine neurological disorders. The basis for this toxicity threshold is unclear. Although polyQ expansions render proteins prone to aggregate into inclusion bodies, this may be a neuronal coping response to more toxic forms of polyQ.

A putative vesicular transporter expressed in Drosophila mushroom bodies that mediates sexual behavior may define a neurotransmitter system.

Vesicular transporters are required for the storage of all classical and amino acid neurotransmitters in synaptic vesicles. Some neurons lack known vesicular transporters, suggesting additional neurotransmitter systems remain unidentified. Insect mushroom bodies (MBs) are critical for several behaviors, including learning, but the neurotransmitters released by the intrinsic Kenyon cells (KCs) remain unknown.

Mountain cedar pollen induces IgE-independent mast cell degranulation, IL-4 production, and intracellular reactive oxygen species generation.

Cedar pollens cause severe allergic disease throughout the world. We have previously characterized allergenic pollen glycoproteins from mountain cedar (Juniperus ashei) that bind to allergen-specific immunoglobulin E (IgE). In the present report, we investigated an alternative pathway of mast cell activation by mountain cedar pollen extract through IgE-independent mechanisms.