Commentary on Phillipou et al., Anorexia Nervosa: Eating Disorder or Body Image Disorder?

Phillipou et al. (2018) assert that anorexia nervosa (AN) should be thought of as a body image disorder (BID), and not as it is currently categorized as an eating disorder (ED, American Psychiatric Association, 2013). They propose that the change in description may serve as a more valuable and accurate portrayal of the illness, and suggest that conceptualizing AN as an ED is too simplistic and thus misleading. Phillipou et al. (2018) examine the view that AN is somehow different from other eating disorders such as pica, rumination disorder, avoidance/restricted food intake disorder, binge eating disorder and bulimia nervosa, because at its core AN is fundamentally an illness of ‘body image’. A parallel objective of Phillipou et al. (2018) is to alter the general public’s perception of AN, from one in which the public believe the AN patient is principally driven by disordered eating behaviour in order to reduce body fat, to one in which the patients’ overriding stimulus is actually body image

The Exocyst Complex in Health and Disease

Exocytosis involves the fusion of intracellular secretory vesicles with the plasma membrane, thereby delivering integral membrane proteins to the cell surface and releasing material into the extracellular space. Importantly, exocytosis also provides a source of lipid moieties for membrane extension. The tethering of the secretory vesicle before docking and fusion with the plasma membrane is mediated by the exocyst complex, an evolutionary conserved octameric complex of proteins. Recent findings indicate that the exocyst complex also takes part in other intra-cellular processes besides secretion. These various functions seem to converge toward defining a direction of membrane growth in a range of systems from fungi to plants and from neurons to cilia. In this review we summarize the current knowledge of exocyst function in cell polarity, signaling and cell-cell communication and discuss implications for plant and animal health and disease

Caudate lobe resections: a single-center experience and evaluation of factors predictive of outcomes

BACKGROUND: Despite the increasing frequency of liver resection for multiple types of disease, caudate lobe resection remains a rare surgical event. The goal of this study is to review our experience and evaluate possible predictors of adverse outcomes in patients undergoing caudate lobectomy. METHODS: We reviewed a 1,900-patient prospective hepato-pancreatico-biliary database from January 2000 to December 2011, identifying 36 hepatectomy patients undergoing caudate lobe resection. Clinicopathologic characteristic and outcome data were compared using chi-square, T-test, ANOVA, Kaplan-Meier, and Cox regression analysis. Primary endpoints were the incidence and severity of complications, and secondary endpoints were blood loss, hospital stay, and transfusion requirements. Patients were also divided in two groups with group A being patients operated on before December 2007 and group B after 2007. We compared the demographics, risk factors, complication rates, and operative details between the two groups. RESULTS: Thirty-six patients underwent caudate lobe resection for cholangiocarcinoma (47.2%), metastatic colorectal cancer (36.1%), hepatocellular carcinoma (8.3%), or benign disease (8.3%). Nine patients (29%) had additional liver resection. Median overall survival (OS) was 21 months. Complications occurred in 52.7% (19/36) of patients with a median grade of 2. Tobacco abuse was associated with an increased risk of operative complications (73.3% vs. 38.9%, p = 0.03). Prior history of cardiac disease was associated with a higher complication rate (87% vs. 42%, p = 0.03). Neoadjuvant chemotherapy, biliary procedures, hepatitis, and prior major abdominal surgery were not predictive of complications. Major complication was also predicted by the volume of RBC transfusion (2.7 vs. 4.1 units, p = 0.003). In our subgroup analysis of the patients undergoing surgery before and after 2007, the two groups were well matched based on age, comorbidities, and risk factors. The complication rates and rates of high-grade complications were similar, but blood loss (600 ml vs. 400 ml, p = 0.03), inflow occlusion time (Pringle time 12.6 vs. 6, p = 0.00), and hospital stay (9.5 vs. 7 days, p = 0.01) were significantly lower in group B. CONCLUSIONS: With appropriate patient selection, caudate lobe resection is an effective component of surgery for hepatic disease. Tobacco use and prior cardiac history increase the risk of complications

Coupling of alpha(1)-Adrenoceptors to ERK1/2 in the Human Prostate

Introduction: alpha(1)-Adrenoceptors are considered critical for the regulation of prostatic smooth muscle tone. However, previous studies suggested further alpha(1)-adrenoceptor functions besides contraction. Here, we investigated whether alpha(1)-adrenoceptors in the human prostate may activate extracellular signal-regulated kinases (ERK1/2). Methods: Prostate tissues from patients undergoing radical prostatectomy were stimulated in vitro. Activation of ERK1/2 was assessed by Western blot analysis. Expression of ERK1/2 was studied by immunohistochemistry. The effect of ERK1/2 inhibition by U0126 on phenylephrine-induced contraction was studied in organ-bath experiments. Results: Stimulation of human prostate tissue with noradrenaline (30 mu M) or phenylephrine (10 mu M) resulted in ERK activation. This was reflected by increased levels of phosphorylated ERK1/2. Expression of ERK1/2 in the prostate was observed in smooth muscle cells. Incubation of prostate tissue with U0126 (30 mu M) resulted in ERK1/2 inhibition. Dose-dependent phenylephrine-induced contraction of prostate tissue was not modulated by U0126. Conclusions: alpha(1)-Adrenoceptors in the human prostate are coupled to ERK1/2. This may partially explain previous observations suggesting a role of alpha(1)-adrenoceptors in the regulation of prostate growth. Copyright (C) 2011 S. Karger AG, Base

Effect of polar amino acid incorporation on Fmoc-diphenylalanine-based tetrapeptides.

Peptide hydrogels show great promise as extracellular matrix mimics due to their tuneable, fibrous nature. Through incorporation of polar cationic, polar anionic or polar neutral amino acids into the Fmoc-diphenylalanine motif, we show that electrostatic charge plays a key role in the properties of the subsequent gelators. Specifically, we show that an inverse relationship exists for biocompatibility in the solution state versus the gel state for cationic and anionic peptides. Finally, we use tethered bilayer lipid membrane (tBLM) experiments to suggest a likely mode of cytotoxicity for tetrapeptides which exhibit cytotoxicity in the solution state

Method for determination of (-102C>T) single nucleotide polymorphism in the human manganese superoxide dismutase promoter

BACKGROUND: Manganese superoxide dismutase (MnSOD) plays a critical role in the detoxification of mitochondrial reactive oxygen species constituting a major cellular defense mechanism against agents that induce oxidative stress. The MnSOD promoter contains an activator protein-2 (AP-2) binding site that modifies transcription of MnSOD. Mutations have been identified in the proximal region of the promoter in human tumor cell lines. One of these mutations (-102C>T) has been shown to change the binding pattern of AP-2 leading to a reduction in transcriptional activity. The aim of our study was to develop a method to identify and determine the frequency of this (-102C>T) polymorphism in human tissues. RESULTS: A new TaqMan allelic discrimination genotype method was successfully applied to genomic DNA samples derived from blood, buccal swabs, snap frozen tissue and paraffin blocks. The polymorphism was shown to be in Hardy-Weinberg Equilibrium in an evaluation of 130 Caucasians from Warsaw, Poland: 44 (33.8%) were heterozygous and 6 (4.6%) were homozygous for -102T. CONCLUSION: This report represents the first description of the MnSOD -102C>T polymorphism in human subjects by a novel Taqman allelic discrimination assay. This method should enable molecular epidemiological studies to evaluate possible associations of this polymorphism with malignancies and other diseases related to reactive oxygen species

Association between manganese superoxide dismutase promoter gene polymorphism and breast cancer survival

BACKGROUND: Manganese superoxide dismutase (MnSOD) plays a critical role in the detoxification of mitochondrial reactive oxygen species, constituting a major cellular defense mechanism against agents that induce oxidative stress. A genetic polymorphism in the mitochondrial targeting sequence of this gene has been associated with increased cancer risk and survival in breast cancer. This base pair transition (-9 T > C) leads to a valine to alanine amino acid change in the mitochondrial targeting sequence. A polymorphism has also been identified in the proximal region of the promoter (-102 C>T) that alters the recognition sequence of the AP-2 transcription factor, leading to a reduction in transcriptional activity. The aim of our study was to investigate possible associations of the -102 C>T polymorphism with overall and relapse-free breast cancer survival in a hospital-based case-only study. MATERIALS AND METHODS: The relationship between the MnSOD -102 C>T polymorphism and survival was examined in a cohort of 291 women who received chemotherapy and/or radiotherapy for incident breast cancer. The MnSOD -102 C>T genotype was determined using a TaqMan allele discrimination assay. Patient survival was evaluated according to the MnSOD genotype using Kaplan–Meier survival functions. Hazard ratios were calculated from adjusted Cox proportional hazards modeling. All statistical tests were two-sided. RESULTS: In an evaluation of all women, there was a borderline significant reduction in recurrence-free survival with either one or both variant alleles (CT + TT) when compared with patients with wild-type alleles (CC) (odds ratio, 0.65; 95% confidence interval, 0.42–1.01). When the analysis was restricted to patients receiving radiation therapy, there was a significant reduction in relapse-free survival in women who were heterozygous for the MnSOD -102 genotype (relative risk, 0.40; 95% confidence interval, 0.18–0.86). Similarly, when the homozygous and heterozygous variant genotypes were combined, there remained a significant reduction in relapse-free survival in this group (hazard ratio, 0.42; 95% confidence interval, 0.20–0.87). CONCLUSION: The MnSOD -102 variant allele appears to be associated with an improved recurrence-free survival in all patients, and more dramatically in subjects who received adjuvant radiation therapy