Frequent recovery of a single clonal type of multidrug-resistant Staphylococcus aureus from patients in two hospitals in Taiwan and China

One hundred thirty-two methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered from patients with S. aureus infections between January 1998 and February 1999 in two hospitals, one located in Taipei, Taiwan, and another in Nanjing, People's Republic of China, were examined for antibiotic susceptibility and for clonal type by a combination of three methods: hybridization of ClaI restriction digests with mecA- and Tn554-specific DNA probes and pulsed-field gel electrophoresis of chromosomal SmaI digests. Selected isolates representing each clonal type were also analyzed by spaA typing, multilocus sequence typing, and a multiplex PCR method capable of identifying the structural type of the staphylococcal cassette chromosome mec (SCCmec) carried by the bacteria. The overwhelming majority of isolates (126 of 132 or 95%) belonged to minor variants of a single clonal type resembling the Brazilian and Hungarian epidemic MRSA clones, which showed a common spaA type and which were either sequence type 239 (ST239) or ST241 (a single-locus variant of ST239) in association with SCCmec type III or IIIA.     

CD4+ T-cell memory: generation and multi-faceted roles for CD4+ T cells in protective immunity to influenza

Summary: We have outlined the carefully orchestrated process of CD4⁺ T‐cell differentiation from naïve to effector and from effector to memory cells with a focus on how these processes can be studied in vivo in responses to pathogen infection. We emphasize that the regulatory factors that determine the quality and quantity of the effector and memory cells generated include (i) the antigen dose during the initial T‐cell interaction with antigen‐presenting cells; (ii) the dose and duration of repeated interactions; and (iii) the milieu of inflammatory and growth cytokines that responding CD4⁺ T cells encounter. We suggest that heterogeneity in these regulatory factors leads to the generation of a spectrum of effectors with different functional attributes. Furthermore, we suggest that it is the presence of effectors at different stages along a pathway of progressive linear differentiation that leads to a related spectrum of memory cells. Our studies particularly highlight the multifaceted roles of CD4⁺ effector and memory T cells in protective responses to influenza infection and support the concept that efficient priming of CD4⁺ T cells that react to shared influenza proteins could contribute greatly to vaccine strategies for influenza.     

Methylglyoxal chronic administration promotes diabetes-like cardiac ischaemia disease in Wistar normal rats

Background and aimsThe influence of lifestyle is well documented, especially the diet regime, in the development of type 2 diabetes (T2D) and associated cardiovascular diseases. Diabetic patients have increased risk of suffering cardiac ischemia and impaired response to such accidents. Methylglyoxal (MG) circulates at high concentration in diabetics' blood and is linked to the development of diabetes chronic complications. We propose that besides promoting the cardiovascular disease, MG may also negatively regulate the endogenous cardioprotection pathways after ischemia.Methods and resultsWe performed a comparative study between three animal groups: normal Wistar (W), type 2 diabetic non-obese Goto-Kakizaki (GK) and normal rats submitted to MG chronic administration (3months) with gradually enhanced concentration, up to 75 mg/Kg (WMG). Hearts were submitted to different experimental conditions: control, ischemia and ischemia-reperfusion. Levels of oxidative stress markers, advanced glycation end-products (AGEs) and their receptors (RAGEs) were evaluated. The serine/threonine protein kinase Akt (Akt), crucial for cardiomyocytes recovery after ischemia, and apoptosis markers were also assessed.Levels of MG, systemic and cardiac oxidative stress markers, AGEs and RAGEs were similar in GK and WMG groups. Akt protein was negatively regulated by MG, leading to impaired apoptotic markers.ConclusionChronic MG administration to normal rodents mimicked most diabetic alterations, being associated with the development of cardiovascular disease and the impairment of survival pathways. Our results demonstrate the negative effect of MG rich diet in healthy animals and suggest the potential of methylglyoxal as a therapeutic target in diabetes.     

A calcium-dependent protease as a potential therapeutic target for Wolfram syndrome

Wolfram syndrome is a genetic disorder characterized by diabetes and neurodegeneration and considered as an endoplasmic reticulum (ER) disease. Despite the underlying importance of ER dysfunction in Wolfram syndrome and the identification of two causative genes, Wolfram syndrome 1 (WFS1) and Wolfram syndrome 2 (WFS2), a molecular mechanism linking the ER to death of neurons and β cells has not been elucidated. Here we implicate calpain 2 in the mechanism of cell death in Wolfram syndrome. Calpain 2 is negatively regulated by WFS2, and elevated activation of calpain 2 by WFS2-knockdown correlates with cell death. Calpain activation is also induced by high cytosolic calcium mediated by the loss of function of WFS1. Calpain hyperactivation is observed in the WFS1 knockout mouse as well as in neural progenitor cells derived from induced pluripotent stem (iPS) cells of Wolfram syndrome patients. A small-scale small-molecule screen targeting ER calcium homeostasis reveals that dantrolene can prevent cell death in neural progenitor cells derived from Wolfram syndrome iPS cells. Our results demonstrate that calpain and the pathway leading its activation provides potential therapeutic targets for Wolfram syndrome and other ER diseases.The endoplasmic reticulum (ER) takes center stage for protein production, redox regulation, calcium homeostasis, and cell death (1, 2). It follows that genetic or acquired ER dysfunction can trigger a variety of common diseases, including neurodegenerative diseases, metabolic disorders, and inflammatory bowel disease (3, 4). Breakdown in ER function is also associated with genetic disorders such as Wolfram syndrome (5–8). It is challenging to determine the exact effects of ER dysfunction on the fate of affected cells in common diseases with polygenic and multifactorial etiologies. In contrast, we reasoned that it should be possible to define the role of ER dysfunction in mechanistically homogenous patient populations, especially in rare diseases with a monogenic basis, such as Wolfram syndrome (9).Wolfram syndrome (OMIM 222300) is a rare autosomal recessive disorder characterized by juvenile-onset diabetes mellitus and bilateral optic atrophy (7). Insulin-dependent diabetes usually occurs as the initial manifestation during the first decade of life, whereas the diagnosis of Wolfram syndrome is invariably later, with onset of symptoms in the second and ensuing decades (7, 10, 11). Two causative genes for this genetic disorder have been identified and named Wolfram syndrome 1 (WFS1) and Wolfram syndrome 2 (WFS2) (12, 13). It has been shown that multiple mutations in the WFS1 gene, as well as a specific mutation in the WFS2 gene, lead to β cell death and neurodegeneration through ER and mitochondrial dysfunction (5, 6, 14–16). WFS1 gene variants are also associated with a risk of type 2 diabetes (17). Moreover, a specific WFS1 variant can cause autosomal dominant diabetes (18), raising the possibility that this rare disorder is relevant to common molecular mechanisms altered in diabetes and other human chronic diseases in which ER dysfunction is involved.Despite the underlying importance of ER malfunction in Wolfram syndrome, and the identification of WFS1 and WFS2 genes, a molecular mechanism linking the ER to death of neurons and β cells has not been elucidated. Here we show that the calpain protease provides a mechanistic link between the ER and death of neurons and β cells in Wolfram syndrome.     

Evaluation of Immunogenicity and Efficacy of Anthrax Vaccine Adsorbed for Postexposure Prophylaxis

Antimicrobials administered postexposure can reduce the incidence or progression of anthrax disease, but they do not protect against the disease resulting from the germination of spores that may remain in the body after cessation of the antimicrobial regimen. Such additional protection may be achieved by postexposure vaccination; however, no anthrax vaccine is licensed for postexposure prophylaxis (PEP). In a rabbit PEP study, animals were subjected to lethal challenge with aerosolized Bacillus anthracis spores and then were treated with levofloxacin with or without concomitant intramuscular (i.m.) vaccination with anthrax vaccine adsorbed (AVA) (BioThrax; Emergent BioDefense Operations Lansing LLC, Lansing, MI), administered twice, 1 week apart. A significant increase in survival rates was observed among vaccinated animals compared to those treated with antibiotic alone. In preexposure prophylaxis studies in rabbits and nonhuman primates (NHPs), animals received two i.m. vaccinations 1 month apart and were challenged with aerosolized anthrax spores at day 70. Prechallenge toxin-neutralizing antibody (TNA) titers correlated with animal survival postchallenge and provided the means for deriving an antibody titer associated with a specific probability of survival in animals. In a clinical immunogenicity study, 82% of the subjects met or exceeded the prechallenge TNA value that was associated with a 70% probability of survival in rabbits and 88% probability of survival in NHPs, which was estimated based on the results of animal preexposure prophylaxis studies. The animal data provide initial information on protective antibody levels for anthrax, as well as support previous findings regarding the ability of AVA to provide added protection to B. anthracis-infected animals compared to antimicrobial treatment alone.     

A systematic review of studies of depression prevalence in university students

Background

Depression is a common health problem, ranking third after cardiac and respiratory diseases as a major cause of disability. There is evidence to suggest that university students are at higher risk of depression, despite being a socially advantaged population, but the reported rates have shown wide variability across settings.

Purpose

To explore the prevalence of depression in university students.

Method

PubMed, PsycINFO, BioMed Central and Medline were searched to identify studies published between 1990 and 2010 reporting on depression prevalence among university students. Searches used a combination of the terms depression, depressive symptoms, depressive disorders, prevalence, university students, college students, undergraduate students, adolescents and/or young adults. Studies were evaluated with a quality rating.

Results

Twenty-four articles were identified that met the inclusion and exclusion criteria. Reported prevalence rates ranged from 10% to 85% with a weighted mean prevalence of 30.6%.

Conclusions

The results suggest that university students experience rates of depression that are substantially higher than those found in the general population. Study quality has not improved since 1990.     

Beliefs regarding the consequences of obesity and ideal weight: an instrument development study

OBJECTIVE: To address the current lack of psychometrically sound measures of beliefs regarding the consequences of obesity and ideal weight that has limited research to-date. METHODS: In phase one, interviews with 22 healthy-weight, overweight and obese individuals were conducted, subjected to theme analysis and used to develop 40 items. In phase two, unsound items were removed following item and principal components analyses of data from a community sample of 188 participants. In phase three, the items selected in phase two were administered to a second workforce population (n=302) to ensure their excellent psychometric properties were stable. In phase four, data were collected from 104 obese clinic attendees to establish the subscales' construct validity. RESULTS: The resultant Obesity Beliefs Scale (OBS) is comprised of three short, reliable, unidimensional and valid subscales written in language suitable for individuals aged 12 years and above. CONCLUSION: The OBS is a psychometrically sound measure of beliefs regarding the consequences obesity and ideal weight. PRACTICE IMPLICATIONS: The OBS has the potential to play a key role in prospective research designed to fully determine the role of beliefs in weight control behaviour. It can also be used to target and assess health education interventions.     

Gaze-shift strategies during functional activity in progressive supranuclear palsy

The relative sparing of visual fixation in parallel with disruption of saccade function in progressive supranuclear palsy (PSP) creates a unique human model for the study of gaze-shift strategies which are adopted when vertical gaze palsy impairs primarily the eye-movement component of gaze control. It was hypothesized that people with PSP would rely on head pitch as a primary component of gaze shift during a platform stepping task and that there would be a predominance of fixation behavior (counter rotation of the eyes during head pitch) while attempting a down-gaze shift. Fourteen subjects with probable and 5 subjects with possible PSP participated in two experiments to measure visual fixation and gaze shift on the same continuum (using a derived vertical gaze fixation score, vGFS). Experiment #1 required gaze fixation during passive head pitch at 0.1–0.2 Hz, whereas experiment #2 required gaze shifts during a continuous platform step on, over, and off task. The primary gaze-shift strategy involved pitching the head downward to compensate for a loss in vertical saccade function. This strategy produced head pitch velocity that leads vertical eye velocity on the order of 200–500 ms. Gaze shifts during platform stepping showed greater fixation suppression (e.g., lower vGFS) in both groups of PSP compared to the visual stabilization task, but some subjects showed “fixation intrusion” during attempted gaze shift. The amount of eye movement was relatively constant when corrected for orbit height, whereas the extent of head pitch varied in proportion to the task demands. The mechanism controlling gaze in PSP, therefore appears to modulate head pitch independently of eye movement, but the gaze strategy seems dependent upon the extent of gaze dysfunction. These findings support the view that the desired gaze signal is parsed into separate eye and head pathways upstream from the burst neurons.