Common genetic variants do not associate with CAD in familial hypercholesterolemia

In recent years, multiple loci dispersed on the genome have been shown to be associated with coronary artery disease (CAD). We investigated whether these common genetic variants also hold value for CAD prediction in a large cohort of patients with familial hypercholesterolemia (FH). We genotyped a total of 41 single-nucleotide polymorphisms (SNPs) in 1701 FH patients, of whom 482 patients (28.3%) had at least one coronary event during an average follow up of 66 years. The association of each SNP with event-free survival time was calculated with a Cox proportional hazard model. In the cardiovascular disease risk factor adjusted analysis, the most significant SNP was rs1122608:G>T in the SMARCA4 gene near the LDL-receptor (LDLR) gene, with a hazard ratio for CAD risk of 0.74 (95% CI 0.49–0.99; P-value 0.021). However, none of the SNPs reached the Bonferroni threshold. Of all the known CAD loci analyzed, the SMARCA4 locus near the LDLR had the strongest negative association with CAD in this high-risk FH cohort. The effect is contrary to what was expected. None of the other loci showed association with CAD.     

Clinical approaches to non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)ranges from simple steatosis to nonalcoholic steatohepatitis(NASH),leading to fibrosis and potentially cirrhosis,and it is one of the most common causes of liver disease worldwide.NAFLD is associated with other medical conditions such as metabolic syndrome,obesity,cardiovascular disease and diabetes.NASH can only be diagnosed through liver biopsy,but noninvasive techniques have been developed to identify patients who are most likely to have NASH or fibrosis,reducing the need for liver biopsy and risk to patients.Disease progression varies between individuals and is linked to a number of risk factors.Mechanisms involved in the pathogenesis are associated with diet and lifestyle,influx of free fatty acids to the liver from adipose tissue due to insulin resistance,hepatic oxidative stress,cytokines production,reduced very low-density lipoprotein secretion and intestinal microbiome.Weight loss through improved diet and increased physical activity has been the cornerstone therapy of NAFLD.Recent therapies such as pioglitazone and vitamin E have been shown to be beneficial.Omega 3 polyunsaturated fatty acids and statins may offer additional benefits.Bariatric surgery should be considered in morbidly obese patients.More research is needed to assess the impact of these treatments on a long-term basis.The objective of this article is to briefly review the diagnosis,management and treatment of this disease in order to aid clinicians in managing these patients.     

Photostability of 2D Organic-Inorganic Hybrid Perovskites

We analyze the behavior of a series of newly synthesized (R-NH₃)₂PbX₄ perovskites and, in particular, discuss the possible reasons which cause their degradation under UV illumination. Experimental results show that the degradation process depends a lot on their molecular components: not only the inorganic part, but also the chemical structure of the organic moieties play an important role in bleaching and photo-chemical reaction processes which tend to destroy perovskites luminescent framework. In addition, we find the spatial arrangement in crystal also influences the photostability course. Following these trends, we propose a plausible mechanism for the photodegradation of the films, and also introduced options for optimized stability.     

Comparing human and mouse salivary glands: A practice guide for salivary researchers

Mice are a widely utilized in vivo model for translational salivary gland research but must be used with caution. Specifically, mouse salivary glands are similar in many ways to human salivary glands (i.e., in terms of their anatomy, histology, and physiology) and are both readily available and relatively easy and affordable to maintain. However, there are some significant differences between the two organisms, and by extension, the salivary glands derived from them must be taken into account for translational studies. The current review details pertinent similarities and differences between human and mouse salivary glands and offers practical guidelines for using both for research purposes.     

Diagnosis of renal metanephric adenoma: relevance of immunohistochemistry and biopsy

Most renal tumors of the adult are carcinomas. Their treatment is surgical, consisting of limited excision or nephrectomy. In some instances, biopsy of the tumor can be performed in order to adapt treatment. We report the case of a 45 year-old woman presenting with renal tumor. A biopsy of the mass showed a metanephric adenoma. No surgical excision was performed because of the benignity of this tumor. Here we develop the interest of immunohistochemistry for differential diagnosis of metanephric adenoma and other "basophilic small cell tumors" of the kidney. We also put the stress on the growing role of biopsy of renal tumor allowing optimal treatment.     

Does surgical approach influence mid- to long-term patient-reported outcomes after primary total hip replacement? A comparison of the 3 main surgical approaches

BackgroundThe most effective surgical approach to total hip replacement (THR) remains controversial. Most studies that have compared approaches have reported only short-term outcome data. It is therefore unclear in the literature if a particular surgical approach offers long-term advantages. The aim of this study was to determine the effect of the 3 main surgical approaches to THR on patient-reported outcomes 5 years after surgery.MethodsAll patients who underwent a THR for osteoarthritis or osteonecrosis between 2008 and 2012 by an anterior, posterior or lateral approach at The Ottawa Hospital in Ontario, Canada, were included in the study. All preoperative and postoperative scores for the Hip Disability and Osteoarthritis Outcome Score (HOOS) and Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC) questionnaires were recorded. Analysis of covariance was used to study the relationship between the amount of change in scores on the HOOS and WOMAC subscales (dependent variables) and the surgical approach. The confounding factors of age, sex, American Society of Anesthesiologists (ASA) class, Charnley classification and body mass index were included in the analysis.ResultsThere were 138 patients (37.6%) in the posterior approach group, 104 (28.3%) in the lateral approach group and 125 (34.1%) in the anterior approach group. There were no significant differences among the 3 groups in terms of Charnley classification, body mass index, sex, ASA class, surgical side and preoperative functional scores. We did not observe any significant differences in the amount of change in the scores for HOOS and WOMAC subscales among the 3 groups. There were also no differences in the final postoperative scores.ConclusionOur findings suggest that the choice of surgical approach in primary THR surgery without revision has no influence on functional outcomes and quality of life after 5 years. Further studies are needed to assess how patient age and sex may influence the functional outcome of individual surgical approaches.     

Efficacy of intravenous cyclosporin in moderately severe ulcerative colitis refractory to steroids

OBJECTIVE: The efficacy of intravenous cyclosporin (CSA) in acute severe ulcerative colitis (UC) is well established. The aim of this study was to evaluate its efficacy in moderately severe colitis refractory to steroids. METHODS: Twenty-six patients (17 men, mean age 41 +/- 14 yr) with UC refractory to steroids treated with CSA were included in this study. Severity was defined according to Truelove criteria. A clinical activity score below 10 during 2 consecutive days defined clinical response. RESULTS: According to Truelove criteria, all patients had moderate UC. CSA was administered IV at a mean daily dose of 3.7 +/- 0,5 mg/kg until response and then orally for 3.5 +/- 2.6 months. A clinical response was achieved in 20/26 patients (76,9%) within 5.7 +/- 2.8 days (5/6 failures were treated by proctocolectomy). During a follow-up of 27.8 +/- 20.8 months, relapse rate was 60% (12/20): 7 patients underwent proctocolectomy and 5 had clinical remission with CSA retreatment (N=4) and steroids (N=1). At the end of follow-up, 12 patients (46%) were in clinical remission, 12 (46%) required colectomy, 1 had chronic active UC and 1 was lost of follow-up. The probability to avoid surgery was 52% at 78 months. The only factor associated with avoidance of surgery was concomitant treatment with azathioprine (P=0.007). Ten reversible adverse events occurred in 9 patients. CONCLUSION: This study shows that CSA is safe and effective in moderately severe steroid resistant UC. Concomitant treatment with azathioprine significantly decreases the rate of subsequent surgery. CSA may act as a "bridge" until the therapeutic action of azathioprine is achieved for maintenance treatment. These results should be further confirmed by a prospective controlled study.