Mycobacterium tuberculosis and Mycobacterium avium inhibit IFN- gamma -induced gene expression by TLR2-dependent and independent pathways.

Mycobacteria-infected macrophages are poor responders to interferon-gamma (IFN-gamma), resulting in decreased expression of IFN-gamma-induced genes. In the present study, we examined the inhibition of IFN-gamma-induced gene expression by Mycobacterium tuberculosis and four different Mycobacterium avium strains in mouse RAW264.7 macrophages. Gamma-irradiated M. tuberculosis inhibited mRNA expression of a panel of six different IFN- gamma-induced genes. All four of the M. avium strains completely inhibited IFN-gamma-induced expression of MHC class II Aalpha and Ebeta mRNA. However, the Mac101 strain, which is serovar 1, inhibited IFN-gamma induction of IFN regulatory factor-1 (IRF-1) and guanylate-binding protein-1 (GBP-1) mRNA to a greater extent than the other M. avium strains, which are serovar 2. In this study, we also show that mycobacteria inhibit gene expression by both toll-like receptor 2 (TLR2)-dependent and independent pathways. The inhibition of IFN-gamma-induced gene expression by M. avium was reduced but not completely blocked in macrophages from TLR2(/) mice. IFN-gamma-induced gene expression was also inhibited by mycobacteria in RAW264.7 cells expressing dominantnegative TLR2 or myeloid differentiation factor 88 (MyD88), further indicating the existence of a pathway independent of TLR2 and MyD88. These data suggest that mycobacteria inhibit IFN-gamma-induced gene expression by multiple pathways involving both TLR2 and non-TLR receptors.     

Mapping brain size and cortical gray matter changes in elderly depression.

BACKGROUND: In elderly depression, volumetric brain imaging findings suggest abnormalities of the frontal lobe, particularly the orbitofrontal cortex, and the hippocampus. No studies to date have mapped cortical abnormalities over the entire brain surface in major depression. Here, we conducted detailed spatial analyses of brain size and gray matter within the cortical mantle in elderly patients with major depression. METHODS: High-resolution, three-dimensional, structural magnetic resonance imaging data and cortical pattern matching methods were used in 24 depressed elderly patients and 19 group-matched controls to measure local brain size and proportions of gray matter at thousands of homologous cortical surface locations. RESULTS: Prominent brain size reductions were observed in the depressed subjects in the orbitofrontal cortex bilaterally. Cortical gray matter measurements revealed significant gray matter increases in the orbitofrontal cortex, adjacent to focal trend level significant decreases of gray matter in the same region. Depressed patients also exhibited significant gray matter increases in parietal cortices, as well as the left temporal cortex. CONCLUSIONS: Complex cortical changes may contribute to the brain size reduction of the orbitofrontal cortex and to the gray matter abnormalities detected in orbitofrontal cortex and temporoparietal cortices, thereby providing a potentially new window into the pathophysiology of elderly depression.     

Corticomotoneuronal dysfunction in ALS patients with different SOD1 mutations.

OBJECTIVE: To examine corticomotoneuronal function in amyotrophic lateral sclerosis (ALS) patients carrying superoxide dismutase 1 (SOD1) mutations using peristimulus time histograms (PSTH). METHODS: Six I113T, 3 A4V, one G41D and one G114A patient were studied along with 21 healthy control subjects. Analyses included comparison with previously reported data from 8 D90A homozygous and 12 sporadic ALS (SALS) patients examined by the authors using identical methodology. RESULTS: Cortical threshold was significantly reduced in A4V patients (41.3%) compared to I113T (58%), SALS (57%) and D90A (71%) patients, as well as healthy controls (49.7%). Estimated excitatory postsynaptic potentials (EPSPs) were significantly larger in A4V patients (4.39 mV) compared to healthy controls (2.95 mV), I113T (2.71 mV) and SALS (2.39 mV) patients. Clinical features and PSTH parameters in I113T were similar to SALS, however, PSTH primary peaks (PP) were significantly more dispersed, 9.5 ms compared to 4ms in SALS. PSTHs from single G41D and G114A patients were unremarkable, apart from large EPSP amplitudes in the G114A patient. CONCLUSIONS: ALS patients with A4V and I113T SOD1 mutations have distinctive corticomotoneuronal changes that are different from those in D90A homozygous and SALS patients. SIGNIFICANCE: PSTH studies should be considered for future in vivo studies of SOD1 pathophysiology in ALS.     

Combining treatment for written and spoken naming.

Individuals with left-hemisphere damage often have concomitant impairment of spoken and written language. Whereas some treatment studies have shown that reading paired with spoken naming can benefit both language modalities, little systematic research has been directed toward the treatment of spelling combined with spoken naming. The purpose of this study was to examine the therapeutic effect of pairing a lexical spelling treatment referred to as Copy and Recall Treatment (CART) with verbal repetition of target words. This approach (CART + Repetition) was compared with treatment using verbal repetition without the inclusion of orthographic training (Repetition Only). Two individuals with moderate aphasia and severe impairment of spelling participated in the study using a multiple baseline design across stimulus sets and treatment conditions. Both participants improved spelling of targeted words as well as spoken naming of those items, but improvement in spoken naming was marked for one individual in the CART + Repetition condition, while the other participant made smaller gains in spoken than written naming irrespective of treatment condition. Consideration of the participant profiles suggested that CART + Repetition provides greater benefit when there is some residual phonological ability and the treatment serves to stimulate links between orthography and phonology.     

An Academic Internist Looks at Euthanasia

This paper points out that to persons unfamiliar with the context and suffering of dying patients, their loved ones, and last, but by no means least, the health care team can only discuss the very concrete question of euthanasia in an abstract way unaware of the fact that this question must, in the final analysis, be differently addressed in different specific patients and under specific circumstances. This paper poses questions which must be addressed and will rarely find a good answer but at least the best among a series of unpalatable options. It again points out the important and legitimate place that emotions play in decision-making.     

What should nurse teachers be doing? A preliminary study

There is little doubt that the role of the nurse teacher is complex and multifaceted in nature. The apparently conflicting demands of NHS trusts and education in the United Kingdom, at the time of integration of nurse education into the higher education sector, further complicates the role. This recognition underlines the need to capture and measure key aspects of nurse teacher function in order to maximize educational gain. Using a comprehensive literature review, focus group discussions and a small number of individual semi-structured interviews, this preliminary study explored the issue of teacher workload, from the perspective of the principal stakeholders in nurse and higher education. Competing research and clinical practice objectives for nurse teachers are identified against a background of changing health care provision, reduced availability of placements and an increased need for evidence-based practice.     

Clinicians into management: on the change agenda or not?

This article examines the issue of drawing medical consultants into managerial decision making. It commences by examining both historically and comparatively the influences on doctors and their reluctance to adopt managerial roles and responsibilities. It progresses to an analysis of the impact of the NHS and Community Care Act particularly in relation to the separation of purchaser and providers and the development of contracting mechanisms. The argument presented suggests that the rapid adoption of the clinical directorate model, as the favoured mode of organisation in acute units, has led to clinicians assuming 'imitation' general manager roles. The authors question whether this is the best use of the unique skills and time of clinicians. They compare with experience in the USA and propose that collaborative working between doctors and general managers is essential in health care. The article suggests a set of tasks for clinician managers and then discusses the issues of training support and development which will be required if clinicians are to perform these tasks effectively.