Interferon and alternative activation of monocyte/macrophages in systemic sclerosis-associated pulmonary arterial hypertension.

Objective: To explore the relationship between biomarkers of pulmonary arterial hypertension (PAH), interferon (IFN)-regulated gene expression, and the alternative activation pathway in systemic sclerosis (SSc).

Methods: Peripheral blood mononuclear cells (PBMCs) were purified from healthy controls, patients with idiopathic PAH, and SSc patients (classified as having diffuse cutaneous SSc, limited cutaneous SSc [lcSSc] without PAH, and lcSSc with PAH). IFN-regulated and "PAH biomarker" genes were compared after supervised hierarchical clustering.

Persistence of yellow fever vaccine RNA in urine.

To evaluate possible persistence of 17D yellow fever vaccine, we tested urine samples from 44 healthy recipients of yellow fever vaccine at varying times up to one year after vaccination. Urine samples from two vaccine recipients had detectable yellow fever virus RNA. The time since vaccination was reported as 21 days for one sample and 198 days for the other sample.

The cystic fibrosis neutrophil: a specialized yet potentially defective cell.

Cystic fibrosis (CF) is one of the commonest genetically inherited diseases in the world. It is characterized by recurrent respiratory tract infections eventually leading to respiratory failure. One of the hallmarks of this disease is a persistent and predominantly neutrophil driven inflammation.

Characterization of the differential response of endothelial cells exposed to normal and elevated laminar shear stress.

Most acute coronary events occur in the upstream region of stenotic atherosclerotic plaques that experience laminar shear stress (LSS) elevated above normal physiological levels. Many studies have described the atheroprotective effect on endothelial behavior of normal physiological LSS (approximately 15 dynes/cm(2)) compared to static or oscillatory shear stress (OSS), but it is unknown whether the levels of elevated shear stress imposed by a stenotic plaque would preserve, enhance or reverse this effect. Therefore we used transcriptomics and related functional analyses to compare human endothelial cells exposed to laminar shear stress of 15 (LSS15-normal) or 75 dynes/cm(2) (LSS75-elevated).

Long-term effects of flooding on mortality in England and Wales, 1994-2005: controlled interrupted time-series analysis.

Background: Limited evidence suggests that being flooded may increase mortality and morbidity among affected householders not just at the time of the flood but for months afterwards. The objective of this study is to explore the methods for quantifying such long-term health effects of flooding by analysis of routine mortality registrations in England and Wales.

Methods: Mortality data, geo-referenced by postcode of residence, were linked to a national database of flood events for 1994 to 2005.

Acquired endocrine resistance in breast cancer: implications for tumour metastasis.

Endocrine therapy is the treatment of choice in hormone receptor-positive breast cancer. However, the effectiveness of these agents is limited by the development of drug resistance, ultimately leading to disease progression and patient mortality. Whilst pre-clinical cell models of acquired endocrine resistance have demonstrated a role for altered growth factor signalling in the development of an endocrine insensitive phenotype, it is becoming apparent that acquisition of endocrine resistance in breast cancer is also accompanied by the development of an adverse cellular phenotype, with resistant cells exhibiting altered adhesive interactions, enhanced migratory and invasive behaviour, and a capacity to induce angiogenic responses in endothelium.

The importance of a travel history in the preoperative assessment of an elective surgical patient.

The authors present the case of a 43-year-old gentleman who was admitted for an elective surgical removal of an eroded gastric band. The patient reported no medical concerns and other than a mild anaemia of haemoglobin of 10.6, his preoperative assessment was non-significant.

Evaluation of inflammatory effects of airborne endotoxin emitted from composting sources.

Because of the lack of effective methodology, the biological effects of environmental endotoxin have not been assessed. Here we have collected and measured airborne endotoxin at different locations around composting sites. Increased endotoxin concentrations were observed close to composting activities and also at nearby boundary areas.

Looking the other way: preventing vector-borne disease among travelers to the United States.

Millions of travelers visit the United States every year during warm months when risk of vector-borne disease is highest. The epidemiology and geographic distribution of the principal vector-borne diseases in the United States are reviewed and recommendations for visitors to reduce their risk of disease are described. Travel advice should focus on preventing Lyme disease, anaplasmosis and babesiosis in the northeast and north central States, West Nile virus disease in western plains States, and Rocky Mountain spotted fever and tularemia in the southeast; other diseases and itineraries requiring particular attention are described.

Is it time for a new yellow fever vaccine?

An inexpensive live attenuated vaccine (the 17D vaccine) against yellow fever has been effectively used to prevent yellow fever for more than 70 years. Interest in developing new inactivated vaccines has been spurred by recognition of rare but serious, sometimes fatal adverse events following live virus vaccination. A safer inactivated yellow fever vaccine could be useful for vaccinating people at higher risk of adverse events from the live vaccine, but could also have broader global health utility by lowering the risk-benefit threshold for assuring high levels of yellow fever vaccine coverage.

Enhanced nociceptive responding in two rat models of depression is associated with alterations in monoamine levels in discrete brain regions.

Altered pain responding in depression is a widely recognized but poorly understood phenomenon. The present study investigated nociceptive responding to acute (thermal and mechanical) and persistent (inflammatory) noxious stimuli in two animal models of depression, the olfactory bulbectomized (OB) and the Wistar-Kyoto (WKY) rat. In addition, this study examined if altered nociceptive behaviour was associated with changes in monoamine levels in discrete brain regions.

Challenges and opportunities associated with preceptored community health clinical experiences.

Preceptored community experiences present challenges different from those of preceptored experiences in the acute care setting. Instead of focusing on psychomotor skills, faculty must address population-based skills and assess students' abilities to practice these skills. Faculty and preceptors' lack of knowledge to teach these skills further complicate the experiences, an issue indirectly related to faculty and nursing shortages.

Limited systemic sclerosis patients with pulmonary arterial hypertension show biomarkers of inflammation and vascular injury.

Background: Pulmonary arterial hypertension (PAH) is a common complication for individuals with limited systemic sclerosis (lSSc). The identification and characterization of biomarkers for lSSc-PAH should lead to less invasive screening, a better understanding of pathogenesis, and improved treatment.

Methods And Findings: Forty-nine PBMC samples were obtained from 21 lSSc subjects without PAH (lSSc-noPAH), 15 lSSc subjects with PAH (lSSc-PAH), and 10 healthy controls; three subjects provided PBMCs one year later.

In vitro developmental potential of macaque oocytes, derived from unstimulated ovaries, following maturation in the presence of glutathione ethyl ester.

Background: The inadequacies of oocyte in vitro maturation (IVM) systems for both non-human primates and humans are evidenced by reduced fertilization and poor embryonic development, and may be partly explained by significantly lower glutathione (GSH) contents compared with in vivo matured (IVO) oocytes. As this influence has not been fully explored, this study investigated the effect of the GSH donor, glutathione ethyl ester (GSH-OEt), on the IVM and development of macaque oocytes as a model of human oocyte IVM.

Methods: Macaque oocytes derived from unstimulated ovaries were cultured in mCMRL-1066 alone or supplemented with 3 or 5 mM GSH-OEt.

Twins: prevalence, problems, and preterm births.

The rate of twin pregnancies in the United States has stabilized at 32 per 1000 births in 2006. Aside from determining chorionicity, first-trimester screening and second-trimester ultrasound scanning should ascertain whether there are structural or chromosomal abnormalities. Compared with singleton births, genetic amniocentesis-related loss at <24 weeks of gestation for twin births is higher (0.

Primate model of metaphase I oocyte in vitro maturation and the effects of a novel glutathione donor on maturation, fertilization, and blastocyst development.

Objective: To assess the effect of glutathione ethyl ester (GSH-OEt) on the development of macaque metaphase (MI) oocytes as a model for human MI oocyte in vitro maturation (IVM).

Design: Prospective cohort study.

Setting: Nonhuman primate assisted reproductive technology program.

Oocyte glutathione and fertilisation outcome of Macaca nemestrina and Macaca fascicularis in in vivo- and in vitro-matured oocytes.

Fertilisation and development of IVM non-human primate oocytes is limited compared with that of in vivo-matured (IVO) oocytes. The present study describes the IVM of macaque oocytes with reference to oocyte glutathione (GSH). Timing of maturation, comparison of IVM media and cysteamine (CYS) supplementation as a modulator of GSH were investigated.

The relationship of health numeracy to cancer screening.

Health numeracy is associated with increased understanding of cancer risk reduction information and improved control of chronic disease. A cross-sectional survey was conducted among a primary care population to evaluate the effect of health numeracy on breast, cervical, and colorectal cancer screening. No association was found between health numeracy and cancer screening.

Household-based sero-epidemiologic survey after a yellow fever epidemic, Sudan, 2005.

From September through early December 2005, an outbreak of yellow fever (YF) occurred in South Kordofan, Sudan, resulting in a mass YF vaccination campaign. In late December 2005, we conducted a serosurvey to assess YF vaccine coverage and to better define the epidemiology of the outbreak in an index village. Of 552 persons enrolled, 95% reported recent YF vaccination, and 25% reported febrile illness during the outbreak period: 13% reported YF-like illness, 4% reported severe YF-like illness, and 12% reported chikungunya-like illness.

Long term expansion of undifferentiated human iPS and ES cells in suspension culture using a defined medium.

Therapeutic application of stem cell derivatives requires large quantities of cells produced in defined media that cannot be produced via conventional adherent culture. We have applied human induced pluripotent stem (hiPS) cells expressing eGFP under control of the OCT4 promoter to establish the expansion of undifferentiated human embryonic stem (hES) and hiPS cells in suspension culture. A defined culture medium has been identified that results in up to six-fold increase in cell numbers within four days.

Relationship between maternal methadone dose at delivery and neonatal abstinence syndrome.

Objective: To estimate the relationship between maternal methadone dose and the incidence of neonatal abstinence syndrome (NAS).

Study Design: We performed a retrospective cohort study of pregnant women treated with methadone for opiate addiction who delivered live-born neonates between 1996 and 2006. Four dose groups, on the basis of total daily methadone dose, were compared (160 mg/d).

Inhibition of focal adhesion kinase suppresses the adverse phenotype of endocrine-resistant breast cancer cells and improves endocrine response in endocrine-sensitive cells.

Acquired resistance to endocrine therapy in breast cancer is a major clinical problem. Previous reports have demonstrated that cell models of acquired endocrine resistance have altered cell-matrix adhesion and a highly migratory phenotype, features which may impact on tumour spread in vivo. Focal adhesion kinase (FAK) is an intracellular kinase that regulates signalling pathways central to cell adhesion, migration and survival and its expression is frequently deregulated in breast cancer.

Developmental potential of bovine oocytes following IVM in the presence of glutathione ethyl ester.

Glutathione (GSH) is synthesised during oocyte maturation and represents the oocyte's main non-enzymatic defence against oxidative stress. Inadequate defence against oxidative stress may be related to poor embryo quality and viability. In the present study, bovine oocytes were matured in vitro in the presence of GSH ethyl ester (GSH-OEt), a cell permeable GSH donor, and its effects on subsequent fertilisation and embryo development were assessed.