Peroxisome Proliferator-Activated Receptor alpha (PPAR alpha) down-regulation in cystic fibrosis lymphocytes

Background: PPARs exhibit anti-inflammatory capacities and are potential modulators of the inflammatory response. We hypothesized that their expression and/or function may be altered in cystic fibrosis (CF), a disorder characterized by an excessive host inflammatory response. Methods: PPARα, β and γ mRNA levels were measured in peripheral blood cells of CF patients and healthy subjects via RT-PCR. PPARα protein expression and subcellular localization was determined via western blot and immunofluorescence, respectively. The activity of PPARα was analyzed by gel shift assay. Results: In lymphocytes, the expression of PPARα mRNA, but not of PPARβ, was reduced (-37%; p < 0.002) in CF patients compared with healthy persons and was therefore further analyzed. A similar reduction of PPARα was observed at protein level (-26%; p < 0.05). The transcription factor was mainly expressed in the cytosol of lymphocytes, with low expression in the nucleus. Moreover, DNA binding activity of the transcription factor was 36% less in lymphocytes of patients (p < 0.01). For PPARα and PPARβ mRNA expression in monocytes and neutrophils, no significant differences were observed between CF patients and healthy persons. In all cells, PPARγ mRNA levels were below the detection limit. Conclusion: Lymphocytes are important regulators of the inflammatory response by releasing cytokines and antibodies. The diminished lymphocytic expression and activity of PPARα may therefore contribute to the inflammatory processes that are observed in CF

Allosteric Modulators of Steroid Hormone Receptors : Structural Dynamics and Gene Regulation

Peer reviewedPublisher PD

Blood lactate levels in 31 female dogs with pyometra

<p>Abstract</p> <p>Background</p> <p>Canine pyometra is a life-threatening disease common in countries where spaying of dogs is not routinely performed. The disease is associated with endotoxemia, sepsis, systemic inflammatory response syndrome (SIRS) and a 3–4% mortality rate. Blood lactate analysis is clinically valuable in predicting prognosis and survival, evaluating tissue perfusion and treatment response in human and veterinary critical care settings. The aims of the present study were to investigate 1) the blood lactate levels of female dogs with pyometra by a hand-held analyser and 2) if these levels are related with the clinical status or other biochemical or hematological disorders.</p> <p>Methods</p> <p>In total 31 female dogs with pyometra admitted for surgical ovariohysterectomy and 16 healthy female control dogs were included in the present study. A complete physical examination including SIRS-status determination was performed. Blood samples for lactate concentrations, hematological and biochemical parameters, acid-base and blood gas analysis and other laboratory parameters were collected and subsequently analysed. The diagnosis pyometra was verified with histopathological examination of the uterus and ovaries. Increased hospitalisation length and presence of SIRS were used as indicators of outcome.</p> <p>Results</p> <p>In the pyometra group the median blood lactate level was 1,6 mmol l^-1(range <0.8–2.7 mmol l^-1). In the control group the median lactate level was 1,2 mmol l^-1(range <0.8–2.1 mmol l^-1). Of the 31 bitches 19 (61%) fulfilled 2 or more criteria for SIRS at inclusion, 10 bitches (32%) fulfilled 3 of the SIRS criteria whereas none accomplished more than 3 criteria. Lactate levels did not differ significantly between the pyometra and control group, or between the SIRS positive and SIRS negative dogs with pyometra. Increased lactate concentration (>2.5 mmol l^-1) was demonstrated in one female dog with pyometra (3%), and was not associated with longer hospitalisation or presence of SIRS. Lactate measurement was not indicative of peritonitis. None of the bitches died during or within two months of the hospital stay. The measurements of temperature, heart rate, respiratory rate, percentage bandforms of neutrophilic granulocytes, α₂-globulins, creatinin, pvCO₂, TCO₂and base excess showed significant differences between the SIRS positive and the SIRS negative pyometra cases.</p> <p>Conclusion</p> <p>Increased blood lactate concentrations were demonstrated in 3% (1/31), and SIRS was present in 61% (19/31) of the female dogs with pyometra. Preoperative lactate levels were not related with presence of SIRS or prolonged hospitalisation. Lactate measurement was not indicative of peritonitis. The value of a single and repeated lactate analysis in more severely affected cases remains to be determined.</p

Virtual Patient Simulations in Health Professions Education: Systematic Review and Meta-Analysis by the Digital Health Education Collaboration.

BACKGROUND: Virtual patients are interactive digital simulations of clinical scenarios for the purpose of health professions education. There is no current collated evidence on the effectiveness of this form of education. OBJECTIVE: The goal of this study was to evaluate the effectiveness of virtual patients compared with traditional education, blended with traditional education, compared with other types of digital education, and design variants of virtual patients in health professions education. The outcomes of interest were knowledge, skills, attitudes, and satisfaction. METHODS: We performed a systematic review on the effectiveness of virtual patient simulations in pre- and postregistration health professions education following Cochrane methodology. We searched 7 databases from the year 1990 up to September 2018. No language restrictions were applied. We included randomized controlled trials and cluster randomized trials. We independently selected studies, extracted data, and assessed risk of bias and then compared the information in pairs. We contacted study authors for additional information if necessary. All pooled analyses were based on random-effects models. RESULTS: A total of 51 trials involving 4696 participants met our inclusion criteria. Furthermore, 25 studies compared virtual patients with traditional education, 11 studies investigated virtual patients as blended learning, 5 studies compared virtual patients with different forms of digital education, and 10 studies compared different design variants. The pooled analysis of studies comparing the effect of virtual patients to traditional education showed similar results for knowledge (standardized mean difference [SMD]=0.11, 95% CI -0.17 to 0.39, I2=74%, n=927) and favored virtual patients for skills (SMD=0.90, 95% CI 0.49 to 1.32, I2=88%, n=897). Studies measuring attitudes and satisfaction predominantly used surveys with item-by-item comparison. Trials comparing virtual patients with different forms of digital education and design variants were not numerous enough to give clear recommendations. Several methodological limitations in the included studies and heterogeneity contributed to a generally low quality of evidence. CONCLUSIONS: Low to modest and mixed evidence suggests that when compared with traditional education, virtual patients can more effectively improve skills, and at least as effectively improve knowledge. The skills that improved were clinical reasoning, procedural skills, and a mix of procedural and team skills. We found evidence of effectiveness in both high-income and low- and middle-income countries, demonstrating the global applicability of virtual patients. Further research should explore the utility of different design variants of virtual patients