Microarray analysis sheds light on the dedifferentiating role of agouti signal protein in murine melanocytes via the Mc1r

The melanocortin-1 receptor (MC1R) is a key regulator of pigmentation in mammals and is tightly linked to an increased risk of skin cancers, including melanoma, in humans. Physiologically activated by α-melanocyte stimulating hormone (αMSH), MC1R function can be antagonized by a secreted factor, agouti signal protein (ASP), which is responsible for the lighter phenotypes in mammals (including humans), and is also associated with increased risk of skin cancer. It is therefore of great interest to characterize the molecular effects elicited by those MC1R ligands. In this study, we determined the gene expression profiles of murine melan-a melanocytes treated with ASP or αMSH over a 4-day time course using genome-wide oligonucleotide microarrays. As expected, there were significant reductions in expression of numerous melanogenic proteins elicited by ASP, which correlates with its inhibition of pigmentation. ASP also unexpectedly modulated the expression of genes involved in various other cellular pathways, including glutathione synthesis and redox metabolism. Many genes up-regulated by ASP are involved in morphogenesis (especially in nervous system development), cell adhesion, and extracellular matrix-receptor interactions. Concomitantly, ASP enhanced the migratory potential and the invasiveness of melanocytic cells in vitro. These results demonstrate the role of ASP in the dedifferentiation of melanocytes, identify pigment-related genes targeted by ASP and by αMSH, and provide insights into the pleiotropic molecular effects of MC1R signaling that may function during development and may affect skin cancer risk.     

Molecular differences between the divergent responses of ovalbumin-specific CD4 T cells to alum-precipitated ovalbumin compared to ovalbumin expressed by Salmonella

CD4 T helper (Th) cell differentiation defined by in vitro cytokine-directed culture systems leaves major gaps in our knowledge of the mechanisms driving divergent Th differentiation. This is evident from our analysis of the response of mouse ovalbumin-specific CD4 T cells to different forms of ovalbumin that induce markedly distinct responses in vivo. We show that live attenuated ovalbumin-expressing Salmonella (SalOVA) induce Th1-associated T-bet and IFN-gamma. Conversely, alum-precipitated ovalbumin (alumOVA) induces the Th2-associated GATA-3 and IL-4. The early diversity occurring within these CD4 T cells isolated 3 days after immunization was assessed using real-time RT-PCR microfluidic cards designed with 384 selected genes. The technique was validated both at the population and single cell levels at different stages of the responses, showing beta2-microglobulin to be a more stably expressed reference mRNA than either beta-actin or 18S RNA. SalOVA was then shown selectively to induce the OVA-specific CD4 T cells to produce many chemokines and pro-inflammatory cytokines, contrasting with alumOVA-induced cells that only produced a few Th2-associated cytokines. Several cytokines and features associated with follicular helper functions were induced in the OVA-specific CD4 T cells by both antigens. Finally, IL-17RB is strongly associated with OVA-specific CD4 T cells responding to alumOVA, suggesting that alum may promote Th2 immune response through a role for the IL-25/IL-17RB pathway.     

Psychopathologie de la dysmorphie musculaire : analyse critique de la littérature internationale

Introduction

Muscle dysmorphia is a contemporary subject of interest officially inscribed in the DSM- 5 in 2013 under the body dysmorphic disorder “muscle dysmorphia”. It does not yet have its own nosographic entity.

Operative vaginal delivery in case of persistent occiput posterior position after manual rotation failure: a 6-month follow-up on pelvic floor function

Purpose

To compare the short- and long-term perineal consequences (at 6 months postpartum) and short-term neonatal consequences of instrumental rotation (IR) to those induced by assisted delivery (AD) in the occiput posterior (OP) position, in case of manual rotation failure.

Methods

A prospective observational cohort study; tertiary referral hospital including all women presenting with persistent OP position who delivered vaginally after manual rotation failure with attempted IR or AD in OP position from September 2015 to October 2016. Maternal and neonatal outcomes of all attempted IR deliveries were compared with OP operative vaginal deliveries. Main outcomes measured were pelvic floor function at 6 months postpartum including Wexner score for anal incontinence and ICIQ-FLUTS for urinary symptoms. Perineal morbidity comprised severe perineal tears, corresponding to third and fourth degree lacerations. Fetal morbidity parameters comprised low neonatal Apgar scores, acidaemia, major and minor fetal injuries and neonatal intensive care unit admissions.

Results

Among 5265 women, 495 presented with persistent OP positions (9.4%) and 111 delivered after manual rotation failure followed by AD delivery: 58 in the IR group and 53 in the AD in OP group. The incidence of anal sphincter injuries was significantly reduced after IR attempt (1.7% vs. 24.5%; p?<?0.001) without increasing neonatal morbidity. At 6 months postpartum, AD in OP position was associated with higher rate of anal incontinence (30% vs. 5.5%, p?=?0.001) and with more urinary symptoms, dyspareunia and perineal pain.

Conclusions

OP operative deliveries are associated with significant perineal morbidity and pelvic floor dysfunction at 6 months postpartum.

     

Effects of ID-alG™ on weight management and body fat mass in high-fat-fed rats

Seaweed extract of Ascophyllum nodosum, ID‐alG?, was evaluated for its chronic effects on weight management in high‐fat‐fed Sprague‐Dawley rats. ID‐alG? was orally administered daily during 9 weeks at doses of 40 and 400 mg/kg/day with fat‐enriched diet (FED) in comparison with two control groups consuming standard diet (negative control) or FED (positive control) and orally treated with vehicle. Body weight, percentage of body fat mass and lipid parameters were measured. After 9 weeks, the oral administration of ID‐alG? at both doses decreased significantly the mean body weight gains (MBWG) of rats submitted to the FED in comparison to the positive control (?6.8% and ?11.8%). ID‐alG? at both doses improved significantly the MBWG of rats and decreased significantly the percentage of body fat mass of rats (?9.8% and ?19.0%), in comparison to the positive control. In the same way, the triglyceride blood level was also significantly improved for the dose of 400 mg/kg/day (?30.6% vs. +49.9% for the positive control); and the dose of 40 mg/kg/day just lead to a trend. Moreover, in both controls and ID‐alG?‐treated groups, total cholesterol, LDL and HDL blood levels were not modified. The seaweed extract of Ascophyllum nodosum, ID‐alG?, demonstrated beneficial effects on weight management of rats submitted to a high‐fat diet. Copyright © 2011 John Wiley & Sons, Ltd.     

Effectiveness of a guideline for venous thromboembolism prophylaxis in elderly post-acute care patients: a multicenter study with systematic ultrasonographic examination

BACKGROUND: Thromboprophylaxis in elderly patients, including post-acute care patients, is at variance with scientific evidence. The purpose of this study was to determine whether a multifaceted intervention was followed by a decrease in deep venous thrombosis (DVT). METHODS: A prospective preintervention-postintervention study was conducted in 1373 patients (preintervention phase, n = 709; postintervention phase, n = 664), aged 65 years or older, enrolled in 33 hospital-based post-acute care facilities in France. An evidence-based guideline addressing pharmacologic and mechanical prophylaxis was implemented through a multifaceted intervention. The main outcome measure was any DVT diagnosed at routine comprehensive ultrasonography performed by registered angiologists. RESULTS: A DVT was found in 91 patients (12.8%) in the preintervention phase and in 52 patients (7.8%) in the postintervention phase (P = .002). The decrease in DVT involved the calf (7.1% vs 3.6%; P = .005) and the proximal venous segments (5.8% vs 4.2%; P = .18) and remained significant after adjusting for risk factors (adjusted odds ratio of any DVT, 0.58; 95% confidence interval, 0.39-0.86). Pharmacologic prophylaxis with either low-molecular-weight heparin at the high-risk dose, unfractionated heparin, and vitamin K antagonist was similar in the 2 study groups, whereas patients in the postintervention group were more likely to use graduated compression stockings (27.4% vs 34.6%; P = .004) and less likely to receive low-molecular-weight heparin at the low-risk dose (24.7% vs 18.5%; P = .006), which was not recommended by our guideline. CONCLUSIONS: A multifaceted intervention addressing venous thromboembolism prophylaxis in post-acute care patients can be followed by a significant decrease in the rate of any DVT in elderly patients. More active interventions are needed to enforce compliance with evidence-based guidelines.     

Pacifiers: a microbial reservoir

The permanent contact between the nipple part of pacifiers and the oral microflora offers ideal conditions for the development of biofilms. This study assessed the microbial contamination on the surface of 25 used pacifier nipples provided by day-care centers. Nine were made of silicone and 16 were made of latex. The biofilm was quantified using direct staining and microscopic observations followed by scraping and microorganism counting. The presence of a biofilm was confirmed on 80% of the pacifier nipples studied. This biofilm was mature for 36% of them. Latex pacifier nipples were more contaminated than silicone ones. The two main genera isolated were Staphylococcus and Candida. Our results confirm that nipples can be seen as potential reservoirs of infections. However, pacifiers do have some advantages; in particular, the potential protection they afford against sudden infant death syndrome. Strict rules of hygiene and an efficient antibiofilm cleaning protocol should be established to answer the worries of parents concerning the safety of pacifiers.     

Differential expression of cyclic nucleotide phosphodiesterases 4 in developing rat lung

During the perinatal period, lungs undergo changes to adapt to air breathing. The genes involved in these changes are developmentally regulated by various signaling pathways, including the cyclic nucleotide cAMP. As PDE4s are critical enzymes for regulation of cAMP levels, the objective of this study was to investigate PDE4's ontogeny in developing rat lung during the perinatal period. Pulmonary PDE4 activity, PDE4A‐D, PDE4B, and PDE4D variant expression levels, PDE4B and PDE4D protein levels, and PDE4D localization in distal lung were determined. PDE4 activity increased towards term, dropped at birth, and increased thereafter to reach a plateau at the end of the second week of life. PDE4B2 and PDE4D long forms demonstrated a pattern of expression that increased markedly at birth. After birth, PDE4D was expressed in alveolar epithelial and mesenchymal cells. The study, therefore, evidenced striking variations in expression patterns among the PDE4 family that differed from changes in global PDE4 activity. Developmental Dynamics 239:2470–2478, 2010. © 2010 Wiley‐Liss, Inc.