Amelioration of bleomycin-induced lung fibrosis in hamsters by dietary supplementation with taurine and niacin: biochemical mechanisms.

Interstitial pulmonary fibrosis induced by intratracheal instillation of bleomycin (BL) involves an excess production of reactive oxygen species, unavailability of adequate levels of NAD and ATP to repair the injured pulmonary epithelium, and an overexuberant lung collagen reactivity followed by deposition of highly cross-linked mature collagen fibrils resistant to enzymatic degradation. In the present study, we have demonstrated that dietary supplementation with taurine and niacin offered almost complete protection against the lung fibrosis in a multidose BL hamster model. The mechanisms for the protective effect of taurine and niacin are multifaceted. These include the ability of taurine to scavenge HOCl and stabilize the biomembrane; niacin's ability to replenish the BL-induced depletion of NAD and ATP; and the combined effect of taurine and niacin to suppress all aspects of BL-induced increases in the lung collagen reactivity, a hallmark of interstitial pulmonary fibrosis. It was concluded from the data presented at this Conference that the combined treatment with taurine and niacin, which offers a multipronged approach, will have great therapeutic potential in the intervention of the development of chemically induced interstitial lung fibrosis in animals and humans

Age differences in physiological responses to self-paced and incremental V˙O2max\dot V O_{2max} testing

Purpose: A self-paced maximal exercise protocol has demonstrated higher $\dot V O_{2max}$ values when compared against traditional tests. The aim was to compare physiological responses to this self-paced $\dot V O_{2max}$ protocol (SPV) in comparison to a traditional ramp $\dot V O_{2max}$ (RAMP) protocol in young (18–30 years) and old (50–75 years) participants. Methods: Forty-four participants (22 young; 22 old) completed both protocols in a randomised, counter-balanced, crossover design. The SPV included 5 × 2 min stages, participants were able to self-regulate their power output (PO) by using incremental ‘clamps’ in ratings of perceived exertion. The RAMP consisted of either 15 or 20 W min$^{−1}$. Results: Expired gases, cardiac output (Q), stroke volume (SV), muscular deoxyhaemoglobin (deoxyHb) and electromyography (EMG) at the vastus lateralis were recorded throughout. Results demonstrated significantly higher $\dot V O_{2max}$ in the SPV (49.68 ± 10.26 ml kg$^{−1}$ min$^{−1}$) vs. the RAMP (47.70 ± 9.98 ml kg$^{−1}$ min$^{−1}$) in the young, but not in the old group (>0.05). Q and SV were significantly higher in the SPV vs. the RAMP in the young (0.05). No differences seen in deoxyHb and EMG for either age groups (>0.05). Peak PO was significantly higher in the SPV vs. the RAMP in both age groups (<0.05). Conclusion: Findings demonstrate that the SPV produces higher $\dot V O_{2max}$, peak Q and SV values in the young group. However, older participants achieved similar $\dot V O_{2max}$ values in both protocols, mostly likely due to age-related differences in cardiovascular responses to incremental exercise, despite them achieving a higher physiological workload in the SPV

Identification of a Putative Network of Actin-Associated Cytoskeletal Proteins in Glomerular Podocytes Defined by Co-Purified mRNAs

The glomerular podocyte is a highly specialized and polarized kidney cell type that contains major processes and foot processes that extend from the cell body. Foot processes from adjacent podocytes form interdigitations with those of adjacent cells, thereby creating an essential intercellular junctional domain of the renal filtration barrier known as the slit diaphragm. Interesting parallels have been drawn between the slit diaphragm and other sites of cell-cell contact by polarized cells. Notably mutations in several genes encoding proteins localized to the foot processes can lead to proteinuria and kidney failure. Mutations in the Wilm's tumor gene (WT1) can also lead to kidney disease and one isoform of WT1, WT1(+KTS), has been proposed to regulate gene expression post-transcriptionally. We originally sought to identify mRNAs associated with WT1(+KTS) through an RNA immunoprecipitation and microarray approach, hypothesizing that the proteins encoded by these mRNAs might be important for podocyte morphology and function. We identified a subset of mRNAs that were remarkably enriched for transcripts encoding actin-binding proteins and other cytoskeletal proteins including several that are localized at or near the slit diaphragm. Interestingly, these mRNAs included those of α-actinin-4 and non-muscle myosin IIA that are mutated in genetic forms of kidney disease. However, isolation of the mRNAs occurred independently of the expression of WT1, suggesting that the identified mRNAs were serendipitously co-purified on the basis of co-association in a common subcellular fraction. Mass spectroscopy revealed that other components of the actin cytoskeleton co-purified with these mRNAs, namely actin, tubulin, and elongation factor 1α. We propose that these mRNAs encode a number of proteins that comprise a highly specialized protein interactome underlying the slit diaphragm. Collectively, these gene products and their interactions may prove to be important for the structural integrity of the actin cytoskeleton in podocytes as well as other polarized cell types

Assessing cognitive insight in nonpsychiatric individuals and outpatients with schizophrenia in Taiwan: an investigation using the Beck Cognitive Insight Scale

<p>Abstract</p> <p>Background</p> <p>The Beck Cognitive Insight Scale (BCIS) was designed for the assessment of the cognitive processes involved in self-reflection and the ability to modify erroneous beliefs and misinterpretations. Studies investigating the factor structure of the BCIS have indicated a two-factor model in the psychotic population. The factor structure of the BCIS, however, has not received much consideration in the nonpsychiatric population. The present study examined the factor structure and validity of the BCIS and compared its scores between nonpsychiatric individuals and outpatients with psychosis.</p> <p>Method</p> <p>The Taiwanese version of the BCIS was administered to 507 nonpsychiatric individuals and 118 outpatients with schizophrenia. The psychometric properties of the BCIS were examined through the following analyses: exploratory and confirmatory factor analyses, reliability, correlation analyses, and discriminative validity.</p> <p>Results</p> <p>The BCIS showed adequate internal consistency and stability over time. Exploratory and confirmatory factor analyses on the 15-item measure indicated a two-factor solution that supported the two dimensions of the Taiwanese BCIS, which was also observed with the original BCIS. Following the construct validation, we obtained a composite index (self-reflectiveness minus self-certainty) of the Taiwanese BCIS that reflected cognitive insight. Consistent with previous studies, our results indicated that psychosis is associated with low self-reflectiveness and high self-certainty, which possibly reflect lower cognitive insight. Our results also showed that better cognitive insight is related to worse depression in patients with schizophrenia spectrum disorders, but not in nonpsychiatric individuals. The receiver operating characteristic (ROC) analyses revealed that the area under the curve (AUC) was 0.731. A composite index of 3 was a good limit, with a sensitivity of 87% and a specificity of 51%.</p> <p>Conclusion</p> <p>The BCIS proved to be useful for measuring cognitive insight in Taiwanese nonpsychiatric and psychotic populations.</p

Emergency department triage: an ethical analysis

<p>Abstract</p> <p>Background</p> <p>Emergency departments across the globe follow a triage system in order to cope with overcrowding. The intention behind triage is to improve the emergency care and to prioritize cases in terms of clinical urgency.</p> <p>Discussion</p> <p>In emergency department triage, medical care might lead to adverse consequences like delay in providing care, compromise in privacy and confidentiality, poor physician-patient communication, failing to provide the necessary care altogether, or even having to decide whose life to save when not everyone can be saved. These consequences challenge the ethical quality of emergency care. This article provides an ethical analysis of "routine" emergency department triage. The four principles of biomedical ethics - viz. respect for autonomy, beneficence, nonmaleficence and justice provide the starting point and help us to identify the ethical challenges of emergency department triage. However, they do not offer a <it>comprehensive </it>ethical view. To address the ethical issues of emergency department triage from a more comprehensive ethical view, the care ethics perspective offers additional insights.</p> <p>Summary</p> <p>We integrate the results from the analysis using four principles of biomedical ethics into care ethics perspective on triage and propose an integrated clinically and ethically based framework of emergency department triage planning, as seen from a comprehensive ethics perspective that incorporates both the principles-based and care-oriented approach.</p

What Is Direct Allorecognition?

Direct allorecognition is the process by which donor-derived major histocompatibility complex (MHC)-peptide complexes, typically presented by donor-derived ‘passenger’ dendritic cells, are recognised directly by recipient T cells. In this review, we discuss the two principle theories which have been proposed to explain why individuals possess a high-precursor frequency of T cells with direct allospecificity and how self-restricted T cells recognise allogeneic MHCpeptide complexes. These theories, both of which are supported by functional and structural data, suggest that T cells recognising allogeneic MHC-peptide complexes focus either on the allopeptides bound to the allo-MHC molecules or the allo-MHC molecules themselves. We discuss how direct alloimmune responses may be sustained long term, the consequences of this for graft outcome and highlight novel strategies which are currently being investigated as a potential means of reducing rejection mediated through this pathway

A Technique for Assessing Upstream Fish Passage Problems at Small-Scale Hydropower Developments

This paper presents an approach for assessing upstream fish passage problems at small hydro projects. Fundamentally, the technique involves evaluating and comparing the swimming and jumping capabilities of a target fish species with the hydraulic characteristics prevailing at the dam face. A knowledge of fish behavior characteristics and the timing and duration of the fish migration period is needed for assessing the overall fish passage potential at the hydro facility