Vitamin D Regulates the Expression of Glucocorticoid Receptors in Blood of Severe Asthmatic Patients.

PURPOSE: Vitamin D (VitD) deficiency is a significant public health concern in many areas around the globe and has been associated with many immune-mediated diseases, including asthma. Severe asthma has been linked to a decreased glucocorticoid receptor (GR) ratio (GR-α/GR-ß ratio), indicating steroid hyporesponsiveness. Using a combination of in silico and in vivo approaches, we aimed to explore the immunomodulatory effect of VitD on asthmatic patients diagnosed with hypovitaminosis D. METHODS: In silico tools were used to identify the regulatory effect of VitD supplementation on GR genes. We measured the expression levels of GR-α and the inactive isoform, GR-ß, in the blood of adult asthmatics diagnosed with hypovitaminosis D before and after VitD supplementation. Moreover, the blood levels of inflammatory cytokines associated with asthma severity were determined. RESULTS: Using an in silico approach, we identified specific genes commonly targeted by VitD as well as corticosteroids, the mainstay of asthma therapy. NR3C1 gene encoding GR was found to be significantly upregulated on Th2 CD4 cells and NK cells. Interestingly, blood expression level of NR3C1 was lower in severe asthmatics compared to nonsevere asthmatics and healthy controls, while the blood level of VitD receptor (VDR) was higher. Upon VitD supplementation of severe asthmatic patients, there was a significant increase in the blood levels of GR-α with no change in GR-ß mRNA expression. VitD supplementation also suppressed the blood levels of IL-17F and IL-4. CONCLUSION: VitD may enhance steroid responsiveness by upregulating the expression of steroid receptor GR-α.

Embrained drives to perform extraordinary roles predict schizotypal traits in the general population.

Some personal drives correspond to extraordinary social roles. Given that behavioral strategies associated with such drives may conflict with those associated with ordinary roles, they could cause behavioral disorganization. To test whether they do so independent of the factors responsible for full-blown schizotypy and schizophrenia, these drives were assessed in the general population. Two hundred and nine healthy volunteers were individually presented with hundreds of names of social roles in experimental psychology conditions. The task of the participant was to decide whether or not (s)he would consider performing the role at any moment of his/her life. Schizotypal traits were measured with the schizotypal personality questionnaire (SPQ), and delusion-like ideations were assessed by the Peters et al. Delusion Inventory. Demographics and social desirability were controlled for. Participants accepting a greater percentage of extraordinary roles had higher SPQ scores. Among the three factors of the SPQ, disorganization was the one best predicted by those percentages. This correlation (r=0.40, P=7.2E-09) was significantly greater (Fisher Z-transform, P=0.003) than the correlation between the percentages of ordinary roles accepted and the SPQ scores (r=0.145, P=0.044). Reaction times revealed no suboptimal cognitive functioning in high accepters of extraordinary roles and further strengthened the drive hypothesis. Their acceptances of roles were done faster and their rejections took longer than those of low accepters (P=5E-12). Culturally embrained drives to do extraordinary roles could thus be an independent factor of the symptoms measured in the normality to schizophrenia continuum.

Real life management of community-acquired Pneumonia in adults in the Gulf region and comparison with practice guidelines: a prospective study.

BACKGROUND: Very few data exist on the management of community-acquired pneumonia (CAP) in patients admitted to hospitals in the Gulf region. The objectives of this study were to describe treatment patterns for CAP in 38 hospitals in five Gulf countries (United Arab Emirates, Kuwait, Bahrain, Oman, and Qatar) and to compare the findings to the most recent Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) guidelines. METHODS: This was a prospective, observational study conducted between January 2009 and February 2011. Adult patients hospitalised (excluding intensive care units) for CAP and subsequently discharged were included. Data were collected retrospectively at hospital discharge, and prospectively during two follow-up visits. Data on medical history, mortality-risk scores, diagnostic criteria, antibiotic treatment, isolated pathogens and clinical and radiographic outcomes were collected. Care practices were compared to the IDSA/ATS guidelines. RESULTS: A total of 684 patients were included. The majority (82.9 %) of patients were classified as low risk for mortality (pneumonia severity index II and III). The majority of patients fulfilled criteria for treatment success at discharge, although only 77.6 % presented a normalised leukocyte count. Overall, the management of CAP in Gulf countries is in line with the IDSA/ATS guidelines. This applied to the diagnosis of CAP, to the identification of high-risk CAP patients, to the identification of etiologic agent responsible for CAP and to the type of treatment despite the fact that combinations of antimicrobial agents were not consistent with the guidelines in 10 % of patients. In all patients, information about Gram's staining was not captured as recommended by the IDSA/ATS and in the majority of patients (>85 %) chest radiography was not systematically performed at the post-discharge follow-up visits. DISCUSSION: The management of CAP in the Gulf region is globally in line with current IDSA/ATS guidelines, although rates of pathogen characterisation and post-discharge follow-up need to be improved. CONCLUSION: Compliance with established guidelines should be encouraged in order to improve the management of the disease in this region.