3,605 research outputs found
PERP, a host tetraspanning membrane protein, is required for Salmonella-induced inflammation
Salmonella enterica Typhimurium induces intestinal inflammation through the activity of type III secreted effector (T3SE) proteins. Our prior results indicate that the secretion of the T3SE SipA and the ability of SipA to induce epithelial cell responses that lead to induction of polymorphonuclear transepithelial migration are not coupled to its direct delivery into epithelial cells from Salmonella. We therefore tested the hypothesis that SipA interacts with a membrane protein located at the apical surface of intestinal epithelial cells. Employing a split ubiquitin yeast-two-hybrid screen, we identified the tetraspanning membrane protein, p53 effector related to PMP-22 (PERP), as a SipA binding partner. SipA and PERP appear to have intersecting activities as we found PERP to be involved in proinflammatory pathways shown to be regulated by SipA. In sum, our studies reveal a critical role for PERP in the pathogenesis of S. Typhimurium, and for the first time demonstrate that SipA, a T3SE protein, can engage a host protein at the epithelial surface
Age-related delay in information accrual for faces: Evidence from a parametric, single-trial EEG approach
Background: In this study, we quantified age-related changes in the time-course of face processing
by means of an innovative single-trial ERP approach. Unlike analyses used in previous studies, our
approach does not rely on peak measurements and can provide a more sensitive measure of
processing delays. Young and old adults (mean ages 22 and 70 years) performed a non-speeded
discrimination task between two faces. The phase spectrum of these faces was manipulated
parametrically to create pictures that ranged between pure noise (0% phase information) and the
undistorted signal (100% phase information), with five intermediate steps.
Results: Behavioural 75% correct thresholds were on average lower, and maximum accuracy was
higher, in younger than older observers. ERPs from each subject were entered into a single-trial
general linear regression model to identify variations in neural activity statistically associated with
changes in image structure. The earliest age-related ERP differences occurred in the time window
of the N170. Older observers had a significantly stronger N170 in response to noise, but this age
difference decreased with increasing phase information. Overall, manipulating image phase
information had a greater effect on ERPs from younger observers, which was quantified using a
hierarchical modelling approach. Importantly, visual activity was modulated by the same stimulus
parameters in younger and older subjects. The fit of the model, indexed by R2, was computed at
multiple post-stimulus time points. The time-course of the R2 function showed a significantly slower
processing in older observers starting around 120 ms after stimulus onset. This age-related delay
increased over time to reach a maximum around 190 ms, at which latency younger observers had
around 50 ms time lead over older observers.
Conclusion: Using a component-free ERP analysis that provides a precise timing of the visual
system sensitivity to image structure, the current study demonstrates that older observers
accumulate face information more slowly than younger subjects. Additionally, the N170 appears to
be less face-sensitive in older observers
Activation of Human Stearoyl-Coenzyme A Desaturase 1 Contributes to the Lipogenic Effect of PXR in HepG2 Cells
The pregnane X receptor (PXR) was previously known as a xenobiotic receptor. Several recent studies suggested that PXR also played an important role in lipid homeostasis but the underlying mechanism remains to be clearly defined. In this study, we found that rifampicin, an agonist of human PXR, induced lipid accumulation in HepG2 cells. Lipid analysis showed the total cholesterol level increased. However, the free cholesterol and triglyceride levels were not changed. Treatment of HepG2 cells with rifampicin induced the expression of the free fatty acid transporter CD36 and ABCG1, as well as several lipogenic enzymes, including stearoyl-CoA desaturase-1 (SCD1), long chain free fatty acid elongase (FAE), and lecithin-cholesterol acyltransferase (LCAT), while the expression of acyl:cholesterol acetyltransferase(ACAT1) was not affected. Moreover, in PXR over-expressing HepG2 cells (HepG2-PXR), the SCD1 expression was significantly higher than in HepG2-Vector cells, even in the absence of rifampicin. Down-regulation of PXR by shRNA abolished the rifampicin-induced SCD1 gene expression in HepG2 cells. Promoter analysis showed that the human SCD1 gene promoter is activated by PXR and a novel DR-7 type PXR response element (PXRE) response element was located at -338 bp of the SCD1 gene promoter. Taken together, these results indicated that PXR activation promoted lipid synthesis in HepG2 cells and SCD1 is a novel PXR target gene. © 2013 Zhang et al
Socioeconomic profile of diabetic patients with and without foot problems
Introduction: To identify the differences in a socioeconomic profile between two cohorts of diabetic patients – one with diabetic foot problems and another without diabetic foot problems. Materials and methods: The cohort with diabetic foot problems (including cellulitis, abscess, osteomyelitis, septic arthritis, gangrene, ulcers, or Charcot joint disease) consisted of 122 diabetic patients, while the other cohort without foot problems consisted of 112 diabetic patients. Both were seen at the National University Hospital from January to April 2007. A detailed protocol was designed and the factors studied included patient profile, average monthly household income, education, compliance to diabetic medication, attendance at clinics for diabetic treatment, exercise, smoking, alcohol consumption, gender, and glycosylated haemoglobin (HbA1C) level. These were studied for significant differences using univariate and stepwise multivariate logistic regression analysis. Results: With multivariate analysis, Malay ethnicity (p<0.001), education of up to secondary school only (p=0.021), low average monthly household income of less than SGD $2,000 (p=0.030), lack of exercise (at least once a week, p=0.04), and elevated HbA1C level (>7.0%; p=0.015) were found to be significantly higher in the cohort with diabetic foot problems than the cohort without. Conclusions: There are significant differences in the socioeconomic factors between diabetic patients with diabetic foot problems and those without
A card game for the treatment of delusional ideas: A naturalistic pilot trial
BACKGROUND: "Michael's game" is a card game which aims at familiarizing healthcare professionals and patients with cognitive behavioral therapy of psychotic symptoms. This naturalistic study tests the feasibility and the impact of the intervention in various naturalistic settings. METHOD: Fifty five patients were recruited in seven centers. They were assessed in pre and post-test with the Peters Delusion Inventory – 21 items (PDI-21). RESULTS: Forty five patients completed the intervention significantly reducing their conviction and preoccupation scores on the PDI-21. CONCLUSION: This pilot study supports the feasibility and effectiveness of "Michael's game" in naturalistic setting. Additional studies could validate the game in a controlled fashion
Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive.
Stressors motivate an array of adaptive responses ranging from \u27fight or flight\u27 to an internal urgency signal facilitating long-term goals. However, traumatic or chronic uncontrollable stress promotes the onset of major depressive disorder, in which acute stressors lose their motivational properties and are perceived as insurmountable impediments. Consequently, stress-induced depression is a debilitating human condition characterized by an affective shift from engagement of the environment to withdrawal. An emerging neurobiological substrate of depression and associated pathology is the nucleus accumbens, a region with the capacity to mediate a diverse range of stress responses by interfacing limbic, cognitive and motor circuitry. Here we report that corticotropin-releasing factor (CRF), a neuropeptide released in response to acute stressors and other arousing environmental stimuli, acts in the nucleus accumbens of naive mice to increase dopamine release through coactivation of the receptors CRFR1 and CRFR2. Remarkably, severe-stress exposure completely abolished this effect without recovery for at least 90 days. This loss of CRF\u27s capacity to regulate dopamine release in the nucleus accumbens is accompanied by a switch in the reaction to CRF from appetitive to aversive, indicating a diametric change in the emotional response to acute stressors. Thus, the current findings offer a biological substrate for the switch in affect which is central to stress-induced depressive disorders
Sudden elevation of liver enzymes in a 64-year-old patient: a case report
Eradication of Helicobacter pylori usually consists of a 7-day course of triple therapy including metronidazole or amoxicillin plus clarithromycin plus a proton pump inhibitor. We report about a rare adverse event of Hp eradication in a patient with moderate chronic and moderate active pangastritis. Shortly after the end of treatment cholestatic hepatitis occurred which was most likely related to clarithromycin, perhaps enhanced by amoxicillin. Since liver dysfunction was self-limited, no further treatment was required. In summary, clinicians should be aware about the presented rare adverse event of Helicobacter pylori eradication treatment for a close monitoring of those patients and rapid management of acute liver failure
A meta-analytic review of stand-alone interventions to improve body image
Objective
Numerous stand-alone interventions to improve body image have been developed. The
present review used meta-analysis to estimate the effectiveness of such interventions, and
to identify the specific change techniques that lead to improvement in body image.
Methods
The inclusion criteria were that (a) the intervention was stand-alone (i.e., solely focused on
improving body image), (b) a control group was used, (c) participants were randomly
assigned to conditions, and (d) at least one pretest and one posttest measure of body
image was taken. Effect sizes were meta-analysed and moderator analyses were conducted.
A taxonomy of 48 change techniques used in interventions targeted at body image
was developed; all interventions were coded using this taxonomy.
Results
The literature search identified 62 tests of interventions (N = 3,846). Interventions produced
a small-to-medium improvement in body image (d+ = 0.38), a small-to-medium reduction in
beauty ideal internalisation (d+ = -0.37), and a large reduction in social comparison tendencies
(d+ = -0.72). However, the effect size for body image was inflated by bias both within
and across studies, and was reliable but of small magnitude once corrections for bias were
applied. Effect sizes for the other outcomes were no longer reliable once corrections for
bias were applied. Several features of the sample, intervention, and methodology moderated
intervention effects. Twelve change techniques were associated with improvements in
body image, and three techniques were contra-indicated.
Conclusions
The findings show that interventions engender only small improvements in body image, and
underline the need for large-scale, high-quality trials in this area. The review identifies effective
techniques that could be deployed in future interventions
Genetic analysis of lung function in inbred mice suggests vitamin D receptor as a candidate gene
Vitamin D receptor (VDR) polymorphisms are associated with an increased asthma incidence in human populations; however, observations in Vdr knockout mice are unclear. The aim of our study was to determine the influence of the genetic variation in Vdr among inbred strains on lung resistance (i.e., dynamic and airway resistance). In an intercross between the strains C57BL/6J (B6) and KK/HlJ (KK), we identified that a significant QTL for dynamic resistance on Chr X was interacting with a QTL on Chr 15. The Chr 15 QTL peak was located in close proximity to the Vdr locus. We further examined if phenotypes of several inbred strains with varying Vdr genotypes differed. Strains with a B6-like genotype on the Vdr locus had significantly lower airway resistance than strains with a KK-like genotype. Vdr knockout mice were examined for dynamic resistance and showed significantly higher resistance than mice with one (i.e., heterozygous) or both copies (i.e., wild-type) of the Vdr. In comparison to B6, the strain A/J is more resistant but carries the same genotype at the Vdr locus. Dietary vitamin D manipulation in the strain A/J did not rescue the high airway resistance phenotype. Finally, we observed that serum vitamin D does not correlate significantly with lung resistance parameters in a survey of 18 strains. Conclusively, Vdr contributes to the phenotypic variation of lung resistance in inbred mice but other molecules in the Vdr pathway and extended network [i.e., Chr X gene(s)] may contribute as well
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