Positioning canine induced pluripotent stem cells (iPSCs) in the reprogramming landscape of naïve or primed state in comparison to mouse and human iPSCs

Aims: Deriving canine-induced pluripotent stem cells (ciPSCs) have paved the way for developing novel cell-based disease models and transplantation therapies in the dog. Though ciPSCs have been derived in the presence of Leukemia inhibitory factor (LIF) as well in the presence of basic fibroblast growth factor (bFGF), the positioning of ciPSCs in the naïve or the primed state of pluripotency remains elusive. This study aims to understand whether canine iPSCs belong to naïve or prime state in comparison to mouse (m) iPSCs and human (h) iPSCs.// Main methods: In the present study, we derived ciPSCs in presence of LIF and compared their state of pluripotency with that of miPSCs and hiPSCs by culturing them in the presence of LIF, bFGF, and LIF + bFGF. Gene expression level at transcript level was performed by RT-PCR and qRT-PCR and at the protein level was analysed by immunofluorescence. We also attempted to understand the pluripotency state using lipid body analysis by bodipy staining and blue fluorescence emission.// Key findings: In contrast to miPSCs, the naïve pluripotent stem cells, ciPSCs showed the expression of FGF5 similar to that of primed pluripotent stem cell, hiPSCs. Compared to miPSCs, ciPSCs cultured in presence of LIF showed enhanced expression of primed pluripotent marker FGF5, similar to hiPSCs cultured in presence of bFGF. Upon culturing in hiPSC culture condition, ciPSCs showed enhanced expression of core pluripotency genes compared to miPSCs cultured in similar condition. However, ciPSCs expressed naïve pluripotent marker SSEA1 similar to miPSCs and lacked the expression of primed state marker SSEA4 unlike hiPSCs. Interestingly, for the first time, we demonstrate the ciPSC pluripotency using lipid body analysis wherein ciPSCs showed enhanced bodipy staining and blue fluorescence emission, reflecting the primed state of pluripotency. ciPSCs expressed higher levels of fatty acid synthase (FASN), the enzyme involved in the synthesis of palmitate, similar to that of hiPSCs and higher than that of miPSCs. As ciPSCs exhibit characteristic properties of both naïve and primed pluripotent state, it probably represents a unique intermediary state of pluripotency that is distinct from that of mice and human pluripotent stem cells.// Significance: Elucidating the pluripotent state of ciPSCs assists in better understanding of the reprogramming events and development in different species. The study would provide a footprint of species-specific differences involved in reprogramming and the potential implication of iPSCs as a tool to analyse evolution

Cognitive behavior therapy

Cognitive behavior therapy (CBT) is one of the most extensively researched psychotherapeutic modalities which is being used either in conjunction with psychotropic drugs or alone in various psychiatric disorders. CBT is a short-term psychotherapeutic approach that is designed to influence dysfunctional emotions, behaviors, and cognitions through a goal-oriented, systematic procedure. Recent advances in CBT suggest that there is a fresh look on a "third wave" CBT that has a greater impact and newer application that may mitigate the sufferings of mentally ill patients

Internet addiction and its determinants among medical students

Background: Exponential use of internet has resulted in internet addiction in recent times. Students are particularly at risk because of their unique personal, social, and academic needs. Objectives: The study was designed to evaluate the prevalence of internet addiction and its determinants among medical students. Materials and Methods: A cross-sectional study was conducted in 282 medical students with the help of semi-structured questionnaire consisting of questions related to demographic information, information related to internet use, and Young's internet addiction test. Results: We found prevalence of internet addiction among medical students to be 58.87% (mild – 51.42%, moderate –7.45%) and significantly associated factors with internet addiction being male gender, staying in private accommodation, lesser age of first internet use, using mobile for internet access, higher expenditure on internet, staying online for longer time, and using internet for social networking, online videos, and watching website with sexual content. Conclusion: Medical students are vulnerable for internet addiction and efforts should be taken to increase awareness and prevent the problem of internet addiction in them

Cholangiolytic Changes in Statin-Induced Liver Injury

Atorvastatin is a commonly used oral cholesterol-lowering agent. Side effects associated with statin therapy include arthralgia, myalgia, dyspepsia, weakness, and headache. Prospective and retrospective studies of drug-induced liver injury have identified statin-induced hepatotoxicity, with atorvastatin being the most commonly cited. Associated liver function test elevations have varied from hepatocellular to cholestatic/mixed pattern. We report a case of a 58-year-old woman that illustrates unusual histologic findings associated with a mixed pattern of statin-induced liver injury. While being treated with atorvastatin, the patient exhibited repeated bouts of abdominal pain over a year associated with biliary tree dilation, variably attributed to postcholecystectomy dilation and stenosis of the ampulla of Vater. Following sphincterotomy, the patient’s bilirubin normalized but the other liver function tests remained elevated. Liver biopsy revealed portal and lobular inflammation with cholangiolysis. The patient’s liver function tests normalized following cessation of atorvastatin therapy

Association of Initial and Serial C-Reactive Protein Levels with Adverse Cardiovascular Events and Death after Acute Coronary Syndrome: A Secondary Analysis of the VISTA-16 Trial

Importance: Higher baseline high-sensitivity C-reactive protein (hsCRP) levels after an acute coronary syndrome (ACS) are associated with adverse cardiovascular outcomes. The usefulness of serial hsCRP measurements for risk stratifying patients after ACS is not well characterized. Objective: To assess whether longitudinal increases in hsCRP measurements during the 16 weeks after ACS are independently associated with a greater risk of a major adverse cardiac event (MACE), all-cause death, and cardiovascular death. Design, Setting, and Participants: Secondary analysis of the double-blind, multicenter, randomized clinical Vascular Inflammation Suppression to Treat Acute Coronary Syndromes for 16 Weeks (VISTA-16) trial conducted between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012), which included 5145 patients from 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America assigned to receive varespladib or placebo on a background of atorvastatin treatment beginning within 96 hours of presentation with an ACS. The present study evaluated data from patients with available baseline and longitudinal hsCRP levels measured at weeks 1, 2, 4, 8, and 16 after randomization to treatment or placebo. Statistical analysis was performed from June 15, 2018, through September 15, 2018. Main Outcomes and Measures: Outcomes were MACE (composite of cardiovascular death, myocardial infarction, nonfatal stroke, or unstable angina with documented ischemia requiring hospitalization), cardiovascular death, and all-cause death after adjustment for baseline clinical, treatment, and laboratory characteristics, including baseline hsCRP levels. Results: Among 4257 patients in this study, 3141 (73.8%) were men and the mean age was 60.3 years (interquartile range [IQR], 53.5-67.8 years). The median 16-week low-density lipoprotein cholesterol level was 64.9 mg/dL (IQR, 50.3-82.3 mg/dL), and the median hsCRP level was 2.4 mg/L (IQR, 1.1-5.2 mg/L). On multivariable analysis, higher baseline hsCRP level (hazard ratio [HR], 1.36 [95% CI, 1.13-1.63]; P =.001) and higher longitudinal hsCRP level (HR, 1.15 [95% CI, 1.09-1.21]; P <.001) were independently associated with MACE. Similar significant and independent associations were shown between baseline and longitudinal hsCRP levels and cardiovascular death (baseline: HR, 1.61 per SD [95% CI, 1.07-2.41], P =.02; longitudinal: HR, 1.26 per SD [95% CI, 1.19-1.34], P <.001) and between baseline and longitudinal hsCRP levels and all-cause death (baseline: HR, 1.58 per SD [95% CI, 1.07-2.35], P =.02; longitudinal: HR, 1.25 per SD [95% CI, 1.18-1.32], P <.001). Conclusions and Relevance: Initial and subsequent increases in hsCRP levels during 16 weeks after ACS were associated with a greater risk of the combined MACE end point, cardiovascular death, and all-cause death despite established background therapies. Serial measurements of hsCRP during clinical follow-up after ACS may help to identify patients at higher risk for mortality and morbidity.