Elevated plasma levels of endothelin are associated with the severity of sepsis and presence of shock in contrast to the levels of atrial natriuretic peptide

Immunoreactive endothelin (ETi) and atrial natriuretic peptide (ANPi) blood levels were measured by radioimmunoassay in patients with clinically defined sepsis. The interaction between these two peptides and their relation to circulatory shock and mortality were studied. All septic patients (n = 16) had significantly higher ETi (22.3 ± 11.1 pg/ml) and ANPi (398.3 ± 154.3 pg/ml) plasma concentrations compared to control subjects (ETi, 4.1 ± 1.2; ANPi, 59.1 ± 14.8 pg/ml; n = 13). ETi levels followed the severity of illness according to the APACHE II scoring system and were higher in patients who did not survive. ETi levels were significantly higher in the presence of shock and bacteraemia. Furthermore, ETi correlated well with plasma lactate (r = 0.83, p < 0.05), but not with renal function. ANPi levels did not show correlation with any of these determinants. Serial blood sampling, six consecutive days after admission, showed that ETi levels gradually decreased in normotensive patients in contrast to patients with septic shock. ANPi levels did not show systematic changes in time, and no relationship was observed between ETi and ANPi levels. These results suggest that plasma ETi levels are indicative for disease severity and might have prognostic significance. The role of ANPi during sepsis remains to be eludicated

Microfluidic Technology in Vascular Research

Vascular cell biology is an area of research with great biomedical relevance. Vascular dysfunction is involved in major diseases such as atherosclerosis, diabetes, and cancer. However, when studying vascular cell biology in the laboratory, it is difficult to mimic the dynamic, three-dimensional microenvironment that is found in vivo. Microfluidic technology offers unique possibilities to overcome this difficulty. In this review, an overview of the recent applications of microfluidic technology in the field of vascular biological research will be given. Examples of how microfluidics can be used to generate shear stresses, growth factor gradients, cocultures, and migration assays will be provided. The use of microfluidic devices in studying three-dimensional models of vascular tissue will be discussed. It is concluded that microfluidic technology offers great possibilities to systematically study vascular cell biology with setups that more closely mimic the in vivo situation than those that are generated with conventional methods

Exploring the role of social capital, self-efficacy and social contagion in shaping lifestyle and mental health among students representing the future healthcare workforce in Palestine: social cohort study protocol

INTRODUCTION: Non-communicable diseases (NCDs) and depression form an unhealthy mix. The project focuses on potentially effective psychosocial factors shaping health-related habits and mental health. The study is conducted among health domain students. Understanding what shapes their health will determine their quality of care. The study is implemented at An-Najah National University in Palestine. This zone of continuous conflict psychological stress is high and mental health problems are stigmatised. METHODS AND ANALYSIS: Students who are enrolled in second and third year will be invited to fill in a baseline and two follow-up online questionnaires. The questionnaires will assess: health behaviours and outcomes (health-related habits, obesity and mental health), main predictors (social capital, social network, self-efficacy), confounders (general and sociodemographic characteristics) and effect modifiers (sense of coherence (SOC) and family SOC). Friendships within participating students will be identified by allowing students to name their friends from a pull-down menu of all students. Descriptive statistics and scores will describe participant's characteristics. The relationship between health behaviour, outcomes and main predictors will be examined by regression and structural equation models. Clustering of health behaviours and outcomes will be assessed by permutation tests. Their spread within the network of friends will be investigated by longitudinal generalised estimating equations. DISCUSSION: The study will identify the prevalence of NCD-related health habits and mental health aspects in the future healthcare workforce in Palestine. It will be the first study to address the role of psychosocial factors for the targeted students. It has the potential to identify targets for promoting physical and mental health among these future professionals. ETHICS AND DISSEMINATION: Ethical approval was obtained from Ethikkommission Nordwest- und Zentralschweiz (EKNZ) in Switzerland and the Institutional Review Board Committee (IRBC) in Palestine. Participation in the study is voluntary and requires informed consent. The data management methodology ensures the confidentiality of the data. The outcomes of the study will be published as scientific papers. In addition, it will be presented in stakeholder conferences and to students at An-Najah National University

Gene expression profiling in murine autoimmune arthritis during the initiation and progression of joint inflammation

We present here an extensive study of differential gene expression in the initiation, acute and chronic phases of murine autoimmune arthritis with the use of high-density oligonucleotide arrays interrogating the entire mouse genome. Arthritis was induced in severe combined immunodeficient mice by using adoptive transfer of lymphocytes from proteoglycan-immunized arthritic BALB/c mice. In this unique system only proteoglycan-specific lymphocytes are transferred from arthritic mice into syngeneic immunodeficient recipients that lack adaptive immunity but have intact innate immunity on an identical (BALB/c) genetic background. Differential gene expression in response to donor lymphocytes that migrated into the joint can therefore be monitored in a precisely timed manner, even before the onset of inflammation. The initiation phase of adoptively transferred disease (several days before the onset of joint swelling) was characterized by differential expression of 37 genes, mostly related to chemokines, interferon-γ and tumor necrosis factor-α signaling, and T cell functions. These were designated early arthritis 'signature' genes because they could distinguish between the naive and the pre-arthritic state. Acute joint inflammation was characterized by at least twofold overexpression of 256 genes and the downregulation of 21 genes, whereas in chronic arthritis a total of 418 genes with an equal proportion of upregulated and downregulated transcripts were expressed differentially. Hierarchical clustering and functional classification of inflammation-related and arthritis-related genes indicated that the most common biological activities were represented by genes encoding interleukins, chemokine receptors and ligands, and by those involved in antigen recognition and processing

Low NOx heavy fuel combustor concept program. Phase 1: Combustion technology generation

The viability of low emission nitrogen oxide (NOx) gas turbine combustors for industrial and utility application. Thirteen different concepts were evolved and most were tested. Acceptable performance was demonstrated for four of the combustors using ERBS fuel and ultralow NOx emissions were obtained for lean catalytic combustion. Residual oil and coal derived liquids containing fuel bound nitrogen (FBN) were also used at test fuels, and it was shown that staged rich/lean combustion was effective in minimizing the conversion of FBN to NOx. The rich/lean concept was tested with both modular and integral combustors. While the ceramic lined modular configuration produced the best results, the advantages of the all metal integral burners make them candidates for future development. An example of scaling the laboratory sized combustor to a 100 MW size engine is included in the report as are recommendations for future work

A Double-Masked, Placebo-Controlled Study of Fluoxetine for Hypochondriasis

This study assessed the efficacy, durability, and tolerability of fluoxetine for hypochondriasis, a disorder for which controlled pharmacological trials are scarce. Fifty-seven patients with hypochondriasis were enrolled: 12 discontinued during the placebo run-in, and 45 were randomized to either fluoxetine or placebo for 12 weeks (acute treatment). Responder status was defined as a Clinical Global Impression rating for hypochondriasis of much or very much improved. Secondary outcome measures included severity of hypochondriasis, somatization, anxiety, and depression. Responders to acute treatment entered a 12-week maintenance phase to week 24. Sustained responders at week 24 entered a 12-week double-masked discontinuation phase. Primary analysis used the intent-to-treat sample. More patients responded with improvement in hypochondriasis when given fluoxetine compared with placebo, starting at week 8 (50.0% vs 19.0%, P = 0.03) and continuing to week 12 (62.5% vs 33.3%, P = 0.05). Mean dose at week 12 dose was 51.4 mg (SD, T23 mg). The acute treatment response was maintained to week 24 with more responders in the fluoxetine compared with the placebo group (54.2% vs 23.8%, P = 0.04). Significant improvement was not noted on the continuous secondary outcomes measures of hypochondriasis, with the exception of the Clinical Global Impression hypochondriasis severity scale at week 24. Likelihood of response was not associated with severity of psychiatric comorbidity. Durability of response after controlled drug discontinuation could not be reasonably assessed, given the small sample size of patients who entered the discontinuation phase (n = 10). Fluoxetine was well tolerated, with no significant differences in discontinuation due to side effects between treatment groups. Fluoxetine is a moderately effective and well-tolerated treatment for hypochondriasis

Intoxication with therapeutic and illicit drug substances and hospital admission to a Dutch university hospital

BACKGROUND: This article describes the retrospective analysis of the patients who presented with a drug-related intoxication to the emergency department of the Erasmus Medical Centre in 2000. METHODS: Data were collected from the emergency department's electronic database and the medical charts of the patients. RESULTS: A total of 243 patients were seen with a drug-related intoxication caused by ingestion of one or more medical substances, drugs of abuse (DOA) or combinations with alcohol. Mono-intoxication occurred in 58% of the patients, predominantly caused by DOA (56 patients), analgesics (17 patients) or benzodiazepines (14 patients). Benzodiazepines (55 patients), analgesics (42 patients), alcohol (42 patients), DOA (40 patients) and antidepressants (23 patients) were predominant in combined intoxications. More than half of the patients (142) were discharged after being treated in the emergency department and 80 patients were admitted to the wards. Eighteen patients were admitted elsewhere and three patients were lost to follow-up. Eve

Lowering Caveolin-1 Expression in Human Vascular Endothelial Cells Inhibits Signal Transduction in Response to Shear Stress

Vascular endothelial cells have an extensive response to physiological levels of shear stress. There is evidence that the protein caveolin-1 is involved in the early phase of this response. In this study, caveolin-1 was downregulated in human endothelial cells by RNAi. When these cells were subjected to a shear stress of 15 dyn/cm(2) for 10 minutes, activation of Akt and ERK1/2 was significantly lower than in control cells. Moreover, activation of Akt and ERK1/2 in response to vascular endothelial growth factor was significantly lower in cells with low levels of caveolin-1. However, activation of integrin-mediated signaling during cell adhesion onto fibronectin was not hampered by lowered caveolin-1 levels. In conclusion, caveolin-1 is an essential component in the response of endothelial cells to shear stress. Furthermore, the results suggest that the role of caveolin-1 in this process lies in facilitating efficient VEGFR2-mediated signaling