Immunohistochemical characterization of fibroblast subpopulations in normal peritoneal tissue and in peritoneal dialysis-induced fibrosis

Peritoneal fibrosis is one of the most common morphological changes observed in continuous ambulatory peritoneal dialysis (CAPD) patients. Both resident fibroblasts and new fibroblast-like cells derived from the mesothelium by epithelial-to-mesenchymal transition are the main cells involved fibrogenesis. In order to establish markers of peritoneal impairment and pathogenic clues to explain the fibrogenic process, we conducted an immunohistochemical study focused on peritoneal fibroblasts. Parietal peritoneal biopsies were collected from four patient groups: normal controls (n=15), non-CAPD uremic patients (n=17), uremic patients on CAPD (n=27) and non-renal patients with inguinal hernia (n=12). To study myofibroblastic conversion of mesothelial cells, -smooth muscle actin (SMA), desmin, cytokeratins and E-cadherin were analyzed. The expression of CD34 by fibroblasts was also analyzed. Fibroblasts from controls and non-CAPD uremic patients showed expression of CD34, but no myofibroblastic or mesothelial markers. The opposite pattern was present during CAPD-related fibrosis. Expression of cytokeratins and E-cadherin by fibroblast-like cells and -SMA by mesothelial and stromal cells supports that mesothelial-to-myofibroblast transition occurs during CAPD. Loss of CD34 expression correlated with the degree of peritoneal fibrosis. The immunophenotype of fibroblasts varies during the progression of fibrosis. Myofibroblasts seem to derive from both activation of resident fibroblasts and local conversion of mesothelial cells.Manuel López-Cabrera and Rafael Selgas contributed equally to the article.     

College student attitudes toward forcible date rape: I. Cognitive predictors

Students completed a questionnaire measuring acceptance of forcible date rape, attitudes toward women, sexual knowledge, sexual experience, tolerance of socially unapproved sexual behavior, and religiosity. Findings suggested that persons relatively more accepting of forcible date rape are less sure it really is rape, have more traditional attitudes toward women, are more selfsexually permissive (i.e., more tolerant of their own socially unapproved of sexual behavior, such as premarital and extramarital sex with friends or casual acquaintances), have less accurate sexual knowledge and, though a large majority blame the male, are slightly more inclined than others to blame society or the situation. These predictor variables accounted for 35% of the variance in attitudes toward forcible date rape and identified correctly about two-thirds of the students classified as nonrejectors of forcible date rape, i.e., those who did not consider the male's behavior definitely unacceptable under any one of nine circumstances, including He spent a lot of money on her. In addition to the emotional and personality variables often cited in rapists, the cognitive predictor variables found may be salient to understanding the etiology of rape.This paper was first presented at meetings of the Society for the Scientific Study of Sex, September 1985, in San Diego, California.     

Evaluating the Impact of a Novel Peer-to-Peer Educational Modality on Knowledge and Attitudes About Perinatal Mood and Anxiety Disorders

Maternal and Child Health Journal - This study assessed whether the use of a peer-to-peer educational book, written and illustrated by women who experienced common mental disorders (CMDs) in the...     

Effects of a single bout of short-duration high-intensity and long-duration low-intensity exercise on insulin resistance and adiponectin/leptin ratio

ObjectivesModerate-intensity exercise improves insulin sensitivity, which may depend on the intensity, duration, and frequency of exercise. We examined the effects of a single bout of short-duration high-intensity exercise (HIE) and long-duration lowintensity exercise (LIE) on insulin sensitivity and the adiponectin/leptin ratio in individuals with different body mass indices (BMIs) who do not exercise regularly.MethodsWe enrolled 42 healthy volunteers aged 20–64 years and divided them into two groups based on BMI: BMI <24 kg/m² and BMI ≥27 kg/m². They were randomly assigned to either the short-duration (20 min) HIE (70%–80% heart rate reserve, HRR) or long-duration (60 min) LIE training groups (30%–40% HRR). Glucose, insulin, adiponectin, and leptin levels were assessed before training and at 0, 30, 60, and 120 min after training.ResultsWe finally analyzed 27 normal weight and 9 obese individuals. No significant differences were observed in the baseline information of both BMI groups. Homeostatic model assessment for insulin resistance significantly improved for both exercise patterns in the normal weight group and for the HIE pattern in the obese group (P < 0.01), whereas the adiponectin/leptin ratio increased significantly only among normal weight participants with the LIE intervention.ConclusionBoth exercise patterns in BMI <24 kg/m² and BMI ≥27 kg/m² benefit on insulin resistance. Therefore, people can choose the way they can fit to improve insulin resistance both short-duration high-intensity exercise and long-duration low-intensity exercise.     

Characterization of an Agarophyton chilense Oleoresin Containing PPARγ Natural Ligands with Insulin-Sensitizing Effects in a C57Bl/6J Mouse Model of Diet-Induced Obesity and Antioxidant Activity in Caenorhabditis elegans

The biomedical potential of the edible red seaweed Agarophyton chilense (formerly Gracilaria chilensis) has not been explored. Red seaweeds are enriched in polyunsaturated fatty acids and eicosanoids, which are known natural ligands of the PPARγ nuclear receptor. PPARγ is the molecular target of thiazolidinediones (TZDs), drugs used as insulin sensitizers to treat type 2 diabetes mellitus. Medical use of TZDs is limited due to undesired side effects, a problem that has triggered the search for selective PPARγ modulators (SPPARMs) without the TZD side effects. We produced Agarophyton chilense oleoresin (Gracilex^®), which induces PPARγ activation without inducing adipocyte differentiation, similar to SPPARMs. In a diet-induced obesity model of male mice, we showed that treatment with Gracilex^® improves insulin sensitivity by normalizing altered glucose and insulin parameters. Gracilex^® is enriched in palmitic acid, arachidonic acid, oleic acid, and lipophilic antioxidants such as tocopherols and β-carotene. Accordingly, Gracilex^® possesses antioxidant activity in vitro and increased antioxidant capacity in vivo in Caenorhabditis elegans. These findings support the idea that Gracilex^® represents a good source of natural PPARγ ligands and antioxidants with the potential to mitigate metabolic disorders. Thus, its nutraceutical value in humans warrants further investigation.     

A simple scoring system to estimate perioperative mortality following liver resection for primary liver malignancy—the Hepatectomy Risk Score (HeRS)

BackgroundSelection of the optimal treatment modality for primary liver cancers remains complex, balancing patient condition, liver function, and extent of disease. In individuals with preserved liver function, liver resection remains the primary approach for treatment with curative intent but may be associated with significant mortality. The purpose of this study was to establish a simple scoring system based on Model for End-stage Liver Disease (MELD) and extent of resection to guide risk assessment for liver resections.MethodsThe 2005–2015 NSQIP database was queried for patients undergoing liver resection for primary liver malignancy. We first developed a model that incorporated the extent of resection (1 point for major hepatectomy) and a MELD-Na score category of low (MELD-Na =6, 1 point), medium (MELD-Na =7–10, 2 points) or high (MELD-Na >10, 3 points) with a score range of 1–4, called the Hepatic Resection Risk Score (HeRS). We tested the predictive value of this model on the dataset using logistic regression. We next developed an optimal multivariable model using backwards sequential selection of variables under logistic regression. We performed K-fold cross validation on both models. Receiver operating characteristics were plotted and the optimal sensitivity and specificity for each model were calculated to obtain positive and negative predictive values.ResultsA total of 4,510 patients were included. HeRS was associated with increased odds of 30-day mortality [HeRS =2: OR =3.23 (1.16–8.99), P=0.025; HeRS =3: OR =6.54 (2.39–17.90), P<0.001; HeRS =4: OR =13.69 (4.90–38.22), P<0.001]. The AUC for this model was 0.66. The AUC for the optimal multivariable model was higher at 0.76. Under K-fold cross validation, the positive predictive value (PPV) and negative predictive value (NPV) of these two models were similar at PPV =6.4% and NPV =97.7% for the HeRS only model and PPV =8.4% and NPV =98.1% for the optimal multivariable model.ConclusionsThe HeRS offers a simple heuristic for estimating 30-day mortality after resection of primary liver malignancy. More complicated models offer better performance but at the expense of being more difficult to integrate into clinical practice.