Missed case of Axenfeld-Rieger syndrome: a case report

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The Renin Angiotensin System (RAS) mediates bifunctional growth regulation in melanoma and is a novel target for therapeutic intervention

Despite emergence of new systemic therapies, metastatic melanoma remains a challenging and often fatal form of skin cancer. The renin–angiotensin system (RAS) is a major physiological regulatory pathway controlling salt–water equilibrium, intravascular volume and blood pressure. Biological effects of the RAS are mediated by the vasoactive hormone angiotensin II (AngII) via two receptor subtypes, AT1R (encoded by AGTR1) and AT2R (encoded by AGTR2). We report decreasing expression and increasing CpG island methylation of AGTR1 in metastatic versus primary melanoma and detection in serum of methylated genomic DNA from the AGTR1 CpG island in metastatic melanoma implying that AGTR1 encodes a tumour suppressor function in melanoma. Consistent with this hypothesis, antagonism of AT1R using losartan or shRNA-mediated knockdown in melanoma cell lines expressing AGTR1 resulted in acquisition of the ability to proliferate in serum-free conditions. Conversely, ectopic expression of AGTR1 in cell lines lacking endogenous expression inhibits proliferation irrespective of the presence of AngII implying a ligand-independent suppressor function for AT1R. Treatment of melanoma cell lines expressing endogenous AT2R with either AngII or the AT2R-selective agonist Y6AII induces proliferation in serum-free conditions whereas the AT2R-specific antagonists PD123319 and EMA401 inhibit melanoma growth and angiogenesis and potentiate inhibitors of BRAF and MEK in cells with BRAF V600 mutations. Our results demonstrate that the RAS has both oncogenic and tumour suppressor functions in melanoma. Pharmacological inhibition of AT2R may provide therapeutic opportunities in melanomas expressing this receptor and AGTR1 CpG island methylation in serum may serve as a novel biomarker of metastatic melanoma

Genome-wide analyses identify common variants associated with macular telangiectasia type 2

Idiopathic juxtafoveal retinal telangiectasis type 2 (macular telangiectasia type 2; MacTel) is a rare neurovascular degenerative retinal disease. To identify genetic susceptibility loci for MacTel, we performed a genome-wide association study (GWAS) with 476 cases and 1,733 controls of European ancestry. Genome-wide significant associations (P < 5 × 10−8) were identified at three independent loci (rs73171800 at 5q14.3, P = 7.74 × 10−17; rs715 at 2q34, P = 9.97 × 10−14; rs477992 at 1p12, P = 2.60 × 10−12) and then replicated (P < 0.01) in an independent cohort of 172 cases and 1,134 controls. The 5q14.3 locus is known to associate with variation in retinal vascular diameter, and the 2q34 and 1p12 loci have been implicated in the glycine/serine metabolic pathway. We subsequently found significant differences in blood serum levels of glycine (P = 4.04 × 10−6) and serine (P = 2.48 × 10−4) between MacTel cases and controls

Papillary renal cell carcinoma with metastatic laparoscopic port site and vaginal involvement: a case report

10.1186/1752-1947-5-131Journal of Medical Case Reports513

The impact of workplace risk factors on the occurrence of neck and upper limb pain: a general population study

BACKGROUND: Work-related neck and upper limb pain has mainly been studied in specific occupational groups, and little is known about its impact in the general population. The objectives of this study were to estimate the prevalence and population impact of work-related neck and upper limb pain. METHODS: A cross-sectional survey was conducted of 10 000 adults in North Staffordshire, UK, in which there is a common local manual industry. The primary outcome measure was presence or absence of neck and upper limb pain. Participants were asked to give details of up to five recent jobs, and to report exposure to six work activities involving the neck or upper limbs. Psychosocial measures included job control, demand and support. Odds ratios (ORs) and population attributable fractions were calculated for these risk factors. RESULTS: The age-standardized one-month period prevalence of neck and upper limb pain was 44%. There were significant independent associations between neck and upper limb pain and: repeated lifting of heavy objects (OR = 1.4); prolonged bending of neck (OR = 2.0); working with arms at/above shoulder height (OR = 1.3); little job control (OR = 1.6); and little supervisor support (OR = 1.3). The population attributable fractions were 0.24 (24%) for exposure to work activities and 0.12 (12%) for exposure to psychosocial factors. CONCLUSION: Neck and upper limb pain is associated with both physical and psychosocial factors in the work environment. Inferences of cause-and-effect from cross-sectional studies must be made with caution; nonetheless, our findings suggest that modification of the work environment might prevent up to one in three of cases of neck and upper limb pain in the general population, depending on current exposures to occupational risk

Complications encountered in the treatment of benign thyroid nodules with US-guided radiofrequency ablation: a multicenter study

PURPOSE: To evaluate clinical aspects and imaging features of complications encountered in the treatment of benign thyroid nodules with radiofrequency (RF) ablation. MATERIALS AND METHODS: Institutional review board approval was obtained for this retrospective study, and informed consent was waived. From June 2002 to September 2009, 1459 patients underwent RF ablation of 1543 thyroid nodules with an RF system with internally cooled electrodes at 13 thyroid centers, which were members of Korean Society of Thyroid Radiology. Numbers and types of major and minor complications were assessed. RESULTS: The authors observed 48 complications (3.3%), 20 major and 28 minor. The major complications were voice changes (n = 15), brachial plexus injury (n = 1), tumor rupture (n = 3), and permanent hypothyroidism (n = 1). The minor complications were hematoma (n = 15), skin burn (n = 4), and vomiting (n = 9). All patients recovered spontaneously except for one with permanent hypothyroidism and one who underwent surgery. CONCLUSION: Although the complication rate of RF ablation is low, various complications may occur; comprehension of complications and suggested technical tips may prevent complications or properly manage those that occur

Calcineurin Inhibition at the Clinical Phase of Prion Disease Reduces Neurodegeneration, Improves Behavioral Alterations and Increases Animal Survival

Prion diseases are fatal neurodegenerative disorders characterized by a long pre-symptomatic phase followed by rapid and progressive clinical phase. Although rare in humans, the unconventional infectious nature of the disease raises the potential for an epidemic. Unfortunately, no treatment is currently available. The hallmark event in prion diseases is the accumulation of a misfolded and infectious form of the prion protein (PrPSc). Previous reports have shown that PrPSc induces endoplasmic reticulum stress and changes in calcium homeostasis in the brain of affected individuals. In this study we show that the calcium-dependent phosphatase Calcineurin (CaN) is hyperactivated both in vitro and in vivo as a result of PrPSc formation. CaN activation mediates prion-induced neurodegeneration, suggesting that inhibition of this phosphatase could be a target for therapy. To test this hypothesis, prion infected wild type mice were treated intra-peritoneally with the CaN inhibitor FK506 at the clinical phase of the disease. Treated animals exhibited reduced severity of the clinical abnormalities and increased survival time compared to vehicle treated controls. Treatment also led to a significant increase in the brain levels of the CaN downstream targets pCREB and pBAD, which paralleled the decrease of CaN activity. Importantly, we observed a lower degree of neurodegeneration in animals treated with the drug as revealed by a higher number of neurons and a lower quantity of degenerating nerve cells. These changes were not dependent on PrPSc formation, since the protein accumulated in the brain to the same levels as in the untreated mice. Our findings contribute to an understanding of the mechanism of neurodegeneration in prion diseases and more importantly may provide a novel strategy for therapy that is beneficial at the clinical phase of the disease

Factors influencing nurses' compliance with Standard Precautions in order to avoid occupational exposure to microorganisms: A focus group study

<p>Abstract</p> <p>Background</p> <p>Nurses may acquire an infection during the provision of nursing care because of occupational exposure to microorganisms. Relevant literature reports that, compliance with Standard Precautions (a set of guidelines that can protect health care professionals from being exposed to microorganisms) is low among nurses. Additionally, high rates of exposure to microorganisms among nurses via several modes (needlesticks, hand contamination with blood, exposure to air-transmitted microorganisms) occur. The aim of the study was to study the factors that influence nurses' compliance with Standard Precaution in order to avoid occupational exposure to pathogens, by employing a qualitative research design.</p> <p>Method</p> <p>A focus group approach was used to explore the issue under study. Four focus groups (N = 30) were organised to elicit nurses' perception of the factors that influence their compliance with Standard Precautions. The Health Belief Model (HBM) was used as the theoretical framework and the data were analysed according to predetermined criteria.</p> <p>Results</p> <p>Following content analysis, factors that influence nurses' compliance emerged. Most factors could be applied to one of the main domains of the HBM: benefits, barriers, severity, susceptibility, cues to action, and self-efficacy.</p> <p>Conclusions</p> <p>Changing current behavior requires knowledge of the factors that may influence nurses' compliance with Standard Precautions. This knowledge will facilitate in the implementation of programs and preventive actions that contribute in avoiding of occupational exposure.</p