Skaaningthomsen0552

Cardiac dysfunction of Fabry disease (FD) has been associated with myofilament damage and cell death as result of α-galactosidase A deficiency and globotriaosylceramide accumulation. We sought to evaluate the role of oxidative stress in FD cardiomyocyte dysfunction. Myocardial tissue from 18 patients with FD was investigated for the expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine by immunohistochemistry. Western blot analysis for nitrotyrosine was also performed. Oxidative damage to DNA was investigated by immunostaining for 8-hydroxydeoxyguanosine (8-OHdG), whereas apoptosis was evaluated by in situ ligation with hairpin probes. iNOS and nitrotyrosine expression was increased in FD hearts compared with hypertrophic cardiomyopathy and normal controls. Remarkably, immunostaining was homogeneously expressed in FD male cardiomyocytes, whereas it was only detected in the affected cardiomyocytes of FD females. Western blot analysis confirmed an increase in FD cardiomyocyte protein nitration compared with controls. 8-OHdG was expressed in 25% of cardiomyocyte nuclei from FD patients, whereas it was absent in controls. The intensity of immunostaining for iNOS/nitrotyrosine correlated with 8-OHdG expression in cardiomyocyte nuclei. Apoptosis of FD cardiomyocytes was 187-fold higher than in controls, and apoptotic nuclei were positive for 8-OHdG. Cardiac dysfunction of FD reflects increased myocardial nitric oxide production with oxidative damage of cardiomyocyte myofilaments and DNA, causing cell dysfunction and death.Histopathologic distinction between benign and malignant epithelia on endoscopic bile duct biopsy can be extremely challenging due to small sample size, crush artifact, and a propensity for marked inflammatory and reactive changes after stent placement. Our previous studies have shown that the insulin-like growth factor II mRNA-binding protein 3, S100P, and the von Hippel-Lindau gene product (pVHL) can help the distinction. This study analyzed 134 endoscopic bile duct biopsy specimens (adenocarcinoma 45, atypical 31, and benign 58) by immunohistochemistry for the expression of maspin, a serine protease inhibitor. The results demonstrated that (1) maspin expression was more frequently detected in malignant than in benign biopsies; (2) malignant biopsies frequently showed diffuse, strong/intermediate, and combined nuclear/cytoplasmic staining patterns for maspin, which were much less commonly seen in benign biopsies; (3) the malignant staining patterns for maspin observed in atypical biopsies were consistent with follow-up data showing that 67% of these patients were subsequently diagnosed with adenocarcinoma; (4) a maspin+/S100P+/pVHL- staining profile was seen in 75% of malignant biopsies but in none of the benign cases. These observations demonstrate that maspin is a useful addition to the diagnostic immunohistochemical panel (S100P, pVHL, and insulin-like growth factor II mRNA-binding protein 3) to help distinguish malignant from benign epithelia on challenging bile duct biopsies.

Our goal was to set criteria for massive ventral hernia and to compare surgical outcomes and quality of life after ventral hernia repair (VHR).

The International Hernia Mesh Registry was queried for patients undergoing VHR from 2007 to 2013. Defect was categorized as massive if the width or length was greater than 15cm or area greater than 150cm(2). Massive VHR was compared to regular VHR.

A total of 878 patients underwent VHR 436 open, 442 laparoscopic with 13 deaths (1.5%) and 45 hernia recurrences (5.1%). Of those, 158 patients (18%) met criteria for massive VHR. Massive VHR patients had longer length of stay (LOS) and operative time and more hematomas, wound infections, wound complications, and pneumonias (P < .05). On multivariate analysis, LOS was longer, and early postoperative pain and activity limitation were greater in massive VHRs (P < .01). Massive VHR in the laparoscopic approach resulted in greater long-term mesh sensation (P < .01).

VHR in massive hernias have increased rates of complications and longer LOS.

VHR in massive hernias have increased rates of complications and longer LOS.

Little data exist regarding the impact of sepsis on deep venous thrombosis (DVT) in colorectal surgery patients. We sought to elucidate this relationship.

Current Procedural Terminology codes were used to identify patients who underwent colorectal surgery as reported to the National Surgical Quality Improvement Program in 2010. The relationship between DVT and sepsis was then explored in a matched population.

Of the 26,554 patients who underwent colorectal surgery, 462 (1.7%) developed a DVT. The largest dependent correlations with DVT were malnutrition (33% vs 57%), emergency operation (15% vs 31%), open operation (58% vs 78%), and prolonged ventilator requirement (5% vs 24%; all P < .001). After propensity score matching, urosepsis (.5% vs 1.9%), organ/space sepsis (1.1% vs 4.8%), pneumosepsis (.5% vs 5.8%), and overall perioperative sepsis (18% vs 39%; all P ≤ .04) were associated with DVT. The strongest independent predictor of DVT was pneumosepsis (odds ratio 15.9, 95% confidence interval 3.7 to 67.2, P < .001).

Perioperative sepsis is a significant risk factor for postoperative DVT in the colorectal surgery population.

Perioperative sepsis is a significant risk factor for postoperative DVT in the colorectal surgery population.

Progress Tests (PTs) draw on a common question bank to assess all students in a programme against graduate outcomes. Theoretically PTs drive deep approaches to learning and reduce assessment-related stress. read more In 2013, PTs were introduced to two year groups of medical students (Years 2 and 4), whereas students in Years 3 and 5 were taking traditional high-stakes assessments. Staged introduction of PTs into our medical curriculum provided a time-limited opportunity for a comparative study. The main purpose of the current study was to compare the impact of PTs on undergraduate medical students' approaches to learning and perceived stress with that of traditional high-stakes assessments. We also aimed to investigate the associations between approaches to learning, stress and PT scores.

Undergraduate medical students (N = 333 and N = 298 at Time 1 and Time 2 respectively) answered the Revised Study Process Questionnaire (R-SPQ-2F) and the Perceived Stress Scale (PSS) at two time points to evaluate change over tient-associated stress is an important finding.

Peripheral nerve injury and bone lesions, well known leprosy complications, lead to deformities and incapacities. The phosphate-regulating gene with homologies to endopeptidase on the X chromosome (PHEX) encodes a homonymous protein (PHEX) implicated in bone metabolism. PHEX/PHEX alterations may result in bone and cartilage lesions. PHEX expression is downregulated by intracellular Mycobacterium leprae (M. leprae) in cultures of human Schwann cells and osteoblasts. M. leprae in vivo effect on PHEX/PHEX is not known.

Cross-sectional observational study of 36 leprosy patients (22 lepromatous and 14 borderline-tuberculoid) and 20 healthy volunteers (HV). The following tests were performed PHEX flow cytometric analysis on blood mononuclear cells, cytokine production in culture supernatant, 25-hydroxyvitamin D (OHvitD) serum levels and (99m)Tc-MDP three-phase bone scintigraphy, radiography of upper and lower extremities and blood and urine biochemistry.

Significantly lower PHEX expression levels were observed in lepromatous patients than in the other groups (χ(2)=16.554, p<0.001 for lymphocytes and χ(2)=13.933, p=0.001 for monocytes). Low levels of 25-(OHvitD) were observed in HV (median=23.0ng/mL) and BT patients (median=27.5ng/mL) and normal serum levels were found in LL patients (median=38.6ng/mL). Inflammatory cytokines, such as TNF, a PHEX transcription repressor, were lower after stimulation with M. leprae in peripheral blood mononuclear cells from lepromatous in comparison to BT patients and HV (χ(2)=10.820, p<0.001).

Downregulation of PHEX may constitute an important early component of bone loss and joint damage in leprosy. The present results suggest a direct effect produced by M. leprae on the osteoarticular system that may use this mechanism.

Downregulation of PHEX may constitute an important early component of bone loss and joint damage in leprosy. The present results suggest a direct effect produced by M. leprae on the osteoarticular system that may use this mechanism.

PCA3 has been included in a nomogram outperforming previous clinical models for the prediction of any prostate cancer (PCa) and high grade PCa (HGPCa) at the initial prostate biopsy (IBx). Our objective is to validate such IBx-specific PCA3-based nomogram. We also aim to optimize the use of this nomogram in clinical practice through the definition of risk groups.

Independent external validation. Clinical and biopsy data from a contemporary cohort of 401 men with the same inclusion criteria to those used to build up the reference's nomogram in IBx. The predictive value of the nomogram was assessed by means of calibration curves and discrimination ability through the area under the curve (AUC). Clinical utility of the nomogram was analyzed by choosing thresholds points that minimize the overlapping between probability density functions (PDF) in PCa and no PCa and HGPCa and no HGPCa groups, and net benefit was assessed by decision curves.

We detect 28% of PCa and 11 % of HGPCa in IBx, contrasting to the 46a calculated probability of having PCa over 40% should be counseled to undergo an IBx if opportunistic screening is required.

Aberrant expression of long noncoding RNAs (lncRNAs) has frequently been reported in cancer studies, including those of colorectal cancer (CRC). Increasing evidence suggests that lncRNAs are significantly correlated with the pathogenesis, development and metastasis of cancer. Loc554202 is a 2166-bp transcript on human chromosome 9p21.3, the expression of which is dysregulated in breast and lung cancer cells. However, its role in CRC remains under investigation.

Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to assess the relative expression of Loc554202 in CRC cell lines and tissues. Gain and/or loss of function approaches were used to investigate the potential functional roles in cell proliferation and apoptosis in vitro and in vivo. qRT-PCR, western-blotting and immunohistochemistry were used to evaluate the mRNA and protein expression of apoptosis-related factors.

Loc554202 was significantly downregulated in cancerous tissues and CRC cell lines compared with adjacent normal tissue and a normal human intestinal epithelial cell line. Low Loc554202 expression was closely associated with advanced pathologic stage and a larger tumor size. The overexpression of Loc554202 decreased the cell proliferation and induced apoptosis in vitro and hindered tumorigenesis in vivo. Loc554202 regulated cell apoptosis partly through the activation of specific caspase cleavage cascades.

Our results suggest that Loc554202 may play an important role in the progression of CRC and could be a candidate prognostic biomarker or a target for new cancer therapies.

Our results suggest that Loc554202 may play an important role in the progression of CRC and could be a candidate prognostic biomarker or a target for new cancer therapies.