Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Traitement du décollement de rétine du pseudophaque: étude rétrospective comparant la vitrectomie sans indentation au traitement ab-externo [Vitrectomy without scleral buckle versus ab-externo approach for pseudophakic retinal detachment: comparative retrospective study].

PURPOSE: Retinal detachment (RD) is a major complication of cataract surgery, which can be treated by either primary vitrectomy without indentation or the scleral buckling procedure. The aim of this study is to compare the results of these two techniques for the treatment of pseudophakic RD. PATIENTS AND METHODS: The charts of 40 patients (40 eyes) treated with scleral buckling for a primary pseudophakic RD were retrospectively studied and compared to the charts of 32 patients (32 eyes) treated with primary vitrectomy without scleral buckle during the same period by the same surgeons. To obtain comparable samples, patients with giant retinal tears, vitreous hemorrhage, and severe preoperative proliferative vitreoretinopathy (PVR) were not included. Minimal follow-up was 6 months. RESULTS: The primary success rate was 84% in the vitrectomy group and 82.5% in the ab-externo group. Final anatomical success was observed in 100% of cases in the vitrectomy group and in 95% of cases in the ab-externo group. Final visual acuity was 0.5 or better in 44% of cases in the vitrectomy group and 37.5% in the ab-externo group. The duration of the surgery was significantly lower in the ab-externo group, whereas the hospital stay tended to be lower in the vitrectomy group. In the vitrectomy group, postoperative PVR developed in 3 eyes and new or undetected breaks were responsible for failure of the initial procedure in 2 eyes. CONCLUSION: Primary vitrectomy appears to be as effective as scleral buckling procedures for the treatment of pseudophakic RD.

Large agminated cellular 'plaque-type' blue nevus surrounding the ear: a case and review.

Large or giant cellular blue nevi are usually congenital and represent a challenge for the physician. Close anatomic structures may be altered by the size of the moles. In this article, we report the case of an uncommon large, agminated, cellular blue nevus of the 'plaque type' in a 42-year-old female. Due to the risks of malignant melanoma development on a large or giant blue nevus, we highlight the importance of proper histopathological diagnosis. Furthermore, because of the possibility that the nevus may invade the bone and cerebral tissues, we discuss the indication of a radiological diagnosis. The accurate correlation to clinical and histopathological findings and appropriate multidisciplinary management can save the lives of patients. © 2013 S. Karger AG, Basel.

The Rare Cancer Network: achievements from 1993 to 2012.

The Rare Cancer Network (RCN), founded in 1993, performs research involving rare tumors that are not common enough to be the focus of prospective study. Over 55 studies have either been completed or are in progress.The aim of the paper is to present an overview of the 30 studies done through the RCN to date, organized by disease site. Five studies focus on breast pathology, including sarcoma, lymphoma, phyllodes tumor, adenoid cystic carcinoma, and ductal carcinoma in situ in young women. Three studies on prostate cancer address prostatic small cell carcinoma and adenocarcinoma of young and elderly patients. Six studies on head and neck cancers include orbital and intraocular lymphoma, mucosal melanoma, pediatric nasopharyngeal carcinoma, olfactory neuroblastoma, and mucosa-associated lymphoid tissue lymphoma of the salivary glands. There were 4 central nervous system studies on patients with cerebellar glioblastoma multiforme, atypical and malignant meningioma, spinal epidural lymphoma and myxopapillary ependymoma. Outside of these disease sites, there is a wide variety of other studies on tumors ranging from uterine leiomyosarcoma to giant cell tumors of the bone. The studies done by the RCN represent a wide range of rare pathologies that were previously only studied in small series or case reports. With further growth of the RCN and collaboration between members our ability to analyze rare tumors will increase and result in better understanding of their behavior and ultimately help direct research that may improve patient outcomes.

Multi-ethnic fine-mapping of 14 central adiposity loci.

The Genetic Investigation of Anthropometric Traits (GIANT) consortium identified 14 loci in European Ancestry (EA) individuals associated with waist-to-hip ratio (WHR) adjusted for body mass index. These loci are wide and narrowing the signals remains necessary. Twelve of 14 loci identified in GIANT EA samples retained strong associations with WHR in our joint EA/individuals of African Ancestry (AA) analysis (log-Bayes factor >6.1). Trans-ethnic analyses at five loci (TBX15-WARS2, LYPLAL1, ADAMTS9, LY86 and ITPR2-SSPN) substantially narrowed the signals to smaller sets of variants, some of which are in regions that have evidence of regulatory activity. By leveraging varying linkage disequilibrium structures across different populations, single-nucleotide polymorphisms (SNPs) with strong signals and narrower credible sets from trans-ethnic meta-analysis of central obesity provide more precise localizations of potential functional variants and suggest a possible regulatory role. Meta-analysis results for WHR were obtained from 77 167 EA participants from GIANT and 23 564 AA participants from the African Ancestry Anthropometry Genetics Consortium. For fine mapping we interrogated SNPs within ± 250 kb flanking regions of 14 previously reported index SNPs from loci discovered in EA populations by performing trans-ethnic meta-analysis of results from the EA and AA meta-analyses. We applied a Bayesian approach that leverages allelic heterogeneity across populations to combine meta-analysis results and aids in fine-mapping shared variants at these locations. We annotated variants using information from the ENCODE Consortium and Roadmap Epigenomics Project to prioritize variants for possible functionality.

Effects of sarcoptic mange on the behaviour of the red fox and influence on other fox-born zoonoses in Geneva, Switzerland

Résumé : Une épidémie de gale sarcoptique (Sarcoptes scabiei) touche le canton de Genève depuis 1996. Nous avons étudié l'impact de cette maladie sur différents caractères comportementaux du renard roux (Vulpes vulpes) : l'écologie alimentaire, les comportements spatiaux et l'activité, ainsi que les contacts sociaux. Nous avons également évalué si la gale pouvait influencer la composition et la transmission de la communauté helminthique intestinale du renard. En effet, cette espèce est l'hôte de parasites qui sont liés à des zoonoses importantes, en particulier le ténia échinocoque du renard (Echinococcus multilocularis) pour lequel Genève est considérée comme une zone de haute endémie. Durant 5 années, des carcasses de renards ont été récoltées sur l'ensemble du canton. Nous les avons disséquées et avons conservé différents échantillons pour des analyses ultérieures. Des données sur le poids, l'âge et le statut reproductif des femelles ont ainsi pu être obtenues. Les contenus stomacaux ont été analysés pour déterminer le régime alimentaire, les intestins pour collecter des helminthes, des échantillons de sang pour faire des sérologies et des échantillons de peau pour récupérer les sarcoptes. Des renards sauvages ont également été capturés et équipés de colliers émetteurs afin de déterminer leur activité et leur utilisation de l'espace. Finalement, nous avons réalisé des affûts sur des terriers et des observations nocturnes à l'aide d'un détecteur thermique afin d'étudier les contacts sociaux. Nous avons ensuite considéré tous ces aspects pour comparer les renards galeux aux individus sains. Trois catégories de gale ont été prises en compte selon l'importance de l'infection. L'épidémie a traversé le canton en 8 ans environ et elle a provoqué une forte diminution des populations de renard. Les animaux malades étaient caractérisés par un poids réduit, ils utilisaient des domaines vitaux réduits et présentaient un rythme d'activité irrégulier. En ce qui concerne le régime alimentaire, les renards galeux avaient souvent des estomacs vides ou contenant peu d'aliments d'origine animale. Cette réduction de l'alimentation ne semble pas seulement être liée à des capacités de prédation réduite, mais également à un désintérêt face à la nourriture. Tous les changements de comportement cités étaient plus marqués chez les animaux soumis à une forte infestation. Dix taxons d'helminthes ont été identifiés dans les intestins des renards analysés. Deux d'entre eux représentent un risque de santé publique: Echinococcus multilocularis et Toxocara carvis. Pour ces helminthes, nous n'avons pas identifié de différences de prévalence entre les renards galeux et les animaux sains, mais la charge parasitaire était significativement supérieure chez les individus galeux, en particulier ceux souffrant d'une infestation importante. Ceci est probablement lié à une susceptibilité accrue des individus qui présentent une condition physique amoindrie et des défenses immunitaire affaiblies. Selon nos résultats, nous pouvons conclure que la gale induit des changements comportementaux importants et que ces changements ont une influence potentielle sur la transmission de la gale elle-même, mais également sur la transmission du reste de la communauté parasitaire de l'hôte. Les individus qui souffrent d'une infestation importante sont susceptibles de provoquer une contamination de l'environnement accrue en ce qui concerne des helminthes pouvant provoquer des zoonoses. La gale apparaît être un facteur à ne pas négliger dans le cadre de la gestion de la faune sauvage, mais également en ce qui concerne des problématiques de santé publique. Summary An epidemic outbreak of sarcoptic mange (Sarcoptes scabiei) has struck the canton of Geneva since 1996. The impact of the disease on various behavioural traits of the main host, the red fox (Vulpes vulpes), was investigated: feeding ecology, spatial behaviour and activity, and social contacts. We also evaluated if mange might have an influence on the composition and transmission of the intestinal helminth community of foxes. Indeed, this species is host of parasites with potential zoonotic importance, particularly the fox tapeworm (Echinococcus multilocularis) for which Geneva is reported as endemic area. During 5 years, red fox carcasses have been collected throughout the canton. They were then dissected and various samples conserved for further analysis. Data on weight, age, and reproductive status of females were obtained. Stomach content were analysed for diet analysis, intestines to recover helminths, blood to proceed to ELISAs and skin samples to check for the presence of Sarcoptes mites. Further, wild foxes were captured and fitted with transmitters in order to determine their activity pattern and space use. Finally, we proceeded to direct observations at dens and using a thermal imaging sensor at night to gain information about social contacts. A comparison between healthy and mangy foxes was made for all these aspects. Three categories of mangy foxes were considered from moderately to severely infected. The epidemic wave crossed the canton in about 8 years and induced a significant reduction in fox densities. Mangy individuals appeared to have reduced body weights, to use more restricted home ranges and exhibited an irregular activity pattern. Regarding food, sick foxes often had empty stomachs and consumed less food items of animal origin. The reduction in food intake appeared to be linked not only to a reduced ability to hunt, but also to a reduced interest in food. The changes observed were particularly pronounced in individuals with severe infestation. Ten helminth taxa were recovered from the intestines on the analysed fox carcasses. Two of them have an importance with regard to human public health: Echinococcus multilocularis and Toxocara cams. The prevalence of these helminths did not differ between healthy and mangy foxes, however the worm burden was significantly higher in mangy foxes, particularly those with severe mange. This is probably linked to an increased susceptibility in individuals with a reduced body condition and weakened immune defences. From our observations, we can conclude that mange induces pronounced behavioural changes in the red fox, and that those changes influence the transmission risks of mange itself, but also of the rest of the parasite community of the host. Individuals with severe mange are for example likely to increase the environment contamination of free living stages of helminths with zoonotic importance. Mange appears thus to represent a factor not to be neglected for the management of wild species and for public health issues.

Electron cryo-microscopy reveals mechanism of action of propranolol on artificial membranes.

The pharmacological activity of several amphiphilic drugs is often related to their ability to interact with biological membranes. Propranolol is an efficient multidrug resistance (MDR) modulator; it is a nonselective beta-blocker and is thought to reduce hypertension by decreasing the cardiac frequency and thus blood pressure. It is used in drug delivery studies in order to treat systemic hypertension. We are interested in the interaction of propranolol with artificial membranes, as liposomes of controllable size are used as biocompatible and protective structures to encapsulate labile molecules, such as proteins, nucleic acids or drugs, for pharmaceutical, cosmetic or chemical applications. We present here a study of the interaction of propranolol, a cationic surfactant, with pure egg phosphatidylcholine (EPC) vesicles. The gradual transition from liposome to micelle of EPC vesicles in the presence of propranolol was monitored by time-resolved electron cryo-microscopy (cryo-EM) under different experimental conditions. The liposome-drug interaction was studied with varying drug/lipid (D/L) ratios and different stages were captured by direct thin-film vitrification. The time-series cryo-EM data clearly illustrate the mechanism of action of propranolol on the liposome structure: the drug disrupts the lipid bilayer by perturbing the local organization of the phospholipids. This is followed by the formation of thread-like micelles, also called worm-like micelles (WLM), and ends with the formation of spherical (globular) micelles. The overall reaction is slow, with the process taking almost two hours to be completed. The effect of a monovalent salt was also investigated by repeating the lipid-surfactant interaction experiments in the presence of KCl as an additive to the lipid/drug suspension. When KCl was added in the presence of propranolol the overall reaction was the same but with slower kinetics, suggesting that this monovalent salt affects the general lipid-to-micelle transition by stabilizing the membrane, presumably by binding to the carbonyl chains of the phosphatidylcholine.

Quelle attitude lors de la découverte de kystes rénaux [Diagnosis of renal cysts].

Evaluation and management of renal cysts Renal cystic diseases are a heterogeneous group of conditions including heritable, developmental, and acquired disorders. They are united by the presence of microscopic or giant fluid-filled cavities and affect both children and adults. The definitive diagnosis of many of the renal cystic diseases requires clinical, radiological, pathological, and genetic analysis. A precise diagnosis is essential for prognosis, treatment, and future genetic counselling.

Roles of PPARβ and PPARγ in mouse placental development

RESUME Les gènes des PPARs jouent des rôles importants dans la régulation du métabolisme énergétique, lipidique et glucidique. Le présent travail, caractérise et analyse les défauts placentaires responsables de la mort embryonnaire des souris mutantes pour PPARβ et pour PPARγ, entre le jour E9.5 et E10.5. Les placentas issus d'embryons PPARP présentent un sévère retard de croissance, alors que les placentas mutants PPARγ montrent de graves défauts vasculaires. Nous montrons que les placentas issus d'embryons PPARβ-/-, au jour E9.5 présentent une réduction prononcée de la couche de cellules géantes, associée à une diminution des niveaux de protéines exprimées par les cellules géantes, tel que le placenta lactogène-I et la « proliferin ». Par ailleurs, nous montrons que le traitement d'un lignée trophoblastique par un ligand spécifique de PPARP augmente considérablement leur différentiation en cellules géantes. Cette différentiation dépendante de la voie de signalisation P13-kinase, s'accompagne d'une élévation de l'expression de l'ADRP, une protéine de structure associée aux vésicules lipidiques. Ainsi nous démontrons que PPAR5 est un régulateur majeur de la différentiation des cellules géantes, lesquelles sont primordiales aussi bien pour l'établissement de la structure placentaire, que pour la fonction endocrine. Par contre, les placentas PPARγ-/- présentent un défaut de vascularisation. Le niveau d'une protéine anti-angiogénique, la « proliferin-related protein », est très basse et ne peut pas contre-balancer l'élévation normale de la protéine pro-angiogénique « proliferin ». La formation des vaisseaux se trouve alors altérée. Ainsi, PPARγ constitue un régulateur majeur de l'activité anti-angiogénique. En conclusion, ce travail fournit de nouveaux éléments sur le rôle complémentaires de PPARβet PPARγ dans les événements complexes qui régissent le développement placentaire. SUMMARY Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors involved in energy homeostasis and growth. Herein, we characterize the placental defects that cause embryonic lethality around E9.5/E10.5 in PPARβ- and in PPARγ-deficient mouse lines. Most but not all PPARβ-null mutants die around E9.5/E10.5 with severe growth retardation. The placentas from PPARβ-/- embryos at E9.5 exhibit a strongly reduced giant cell layer, associated with reduced levels of proteins expressed by giant cells such as Placental lactogen-I and Proliferin. Ectopic treatment of a rat trophoblast cell line with PPARβ ligand markedly accelerated PI3 kinase-dependent giant cell differentiation. In addition, we demonstrate that ADRP, a pen-related lipid droplet-bound protein, is up-regulated by PPARβ in differentiated Rcho-1 cells. These results indicate that PPARβ is a crucial regulator of the differentiation secondary giant cells, which play a major role in the establishment of the placental structure as well as an important endocrine function. In contrast, the main alteration of the PPARγ-null placentas concerns the vasculogenesis. We show that in these placentas, the level of the anti-angiogenic proliferin-related protein is very low, and cannot balance the normal elevation of the pro-angiogenic proliferin expression, leading to the defective placental vessel formation. Consistently, the dramatic increase of PPARγ expression in late stage of gestation in wild-type mice is likely a major regulator of the anti-angiogenic activity, particularly important at the end of the pregnancy. This work emphasizes the important and complementary roles of PPARβ and PPARγ in mouse placental development and provides new tools for understanding the complex regulatory events that governs placental development and function. Understanding the function of PPARβ and PPARγ are of crucial interest with respect to human placental development and associated pathologies.

Significant genetic and phenotypic changes arising from clonal growth of a single spore of an arbuscular mycorrhizal fungus over multiple generations.

Arbuscular mycorrhizal fungi (AMF) are highly successful plant symbionts. They reproduce clonally producing multinucleate spores. It has been suggested that some AMF harbor genetically different nuclei. However, recent advances in sequencing the Glomus irregulare genome have indicated very low within-fungus polymorphism. We tested the null hypothesis that, with no genetic differences among nuclei, no significant genetic or phenotypic variation would occur among clonal single spore lines generated from one initial AMF spore. Furthermore, no additional variation would be expected in the following generations of single spore lines. Genetic diversity contained in one initial spore repeatedly gave rise to genetically different variants of the fungus with novel phenotypes. The genetic changes represented quantitative changes in allele frequencies, most probably as a result of changes in the frequency of genetic variation partitioned on different nuclei. The genetic and phenotypic variation is remarkable, given that it arose repeatedly from one clonal individual. Our results highlight the dynamic nature of AMF genetics. Even though within-fungus genetic variation is low, some is probably partitioned among nuclei and potentially causes changes in the phenotype. Our results are important for understanding AMF genetics, as well as for researchers and biotechnologists hoping to use AMF genetic diversity for the improvement of AMF inoculum.

Long-term Outcome after Liver Resection for Hepatocellular Carcinoma Larger than 10 cm.

BACKGROUND: The purpose of the present study was to analyze long-term survival and disease-free survival after liver resection for giant hepatocellular carcinoma (HCC) ≥ 10 cm compared to HCC < 10 cm in diameter. The surgical approach in the treatment of giant HCC may achieve long-term survival and disease-free survival comparable to treatment of smaller lesions. METHODS: This retrospective analysis was a monocentric study conducted in a tertiary university center. It included 101 patients from 114 consecutive liver resections for HCC, separated into two groups: those with tumors less than 10 cm in diameter (small HCC; n = 79) and those with tumors larger than 10 cm (giant HCC; n = 22). The main outcome measures were overall five-year survival, five-year disease-free survival, recurrence rate, perioperative mortality at 30 days, surgical complication rate, and re-intervention rate. RESULTS: The two groups were homogeneously distributed, apart from cirrhosis, which was found more frequently in the group with small HCC (77 vs. 41 %; p = 0.0013). Both median survival (24 vs. 27 months; p = 0.0085) and overall 5-year survival (21 vs. 45; p = 0.04) were significantly poorer in the small HCC group compared to the giant HCC group. There were no differences en terms of recurrence rate, pattern, and timing. CONCLUSIONS: Liver resection for HCC larger than 10 cm is a valuable option in selected patients, one that provides overall survival and disease-free survival comparable to smaller lesions. Functional reserves of the liver, more than the size of the lesion, may be important in patient selection for surgical resection.

Cerebrospinal fluid biomarkers of central nervous system dysfunction in HIV-infected patients

Background :¦In addition to opportunistic infections of the central nervous system (CNS), which are due to immunosuppression related to HIV, the latter virus, itself, can cause neuropathological abnormalities which are located mainly in the basal ganglia and are characterized by microglial giant cells, reactive astrocytosis and perivascular monocytes. This HIV encephalopathy is characterized, clinically, by psycho-motor slowing, memory loss, difficulties in complex tasks requiring executive functions, as well as motor disorders .These cognitive deficits are grouped under the acronym of HIV-associated neurocognitive disorders (HAND). In fact, HANDs are subdivided in three groups in accordance with the severity of the cognitive impairment: Asymptomatic Neurocognitive Impairment (ANI), Mild/moderate Neurocognitive Disorders (MND) and HIV Associated Dementia (HAD).¦While the incidence of HAD has significantly decreased in the era of combined antiretrobiral therapy (cART), the prevalence of milder forms of HIV-associated neurocognitive disorders HAND seem to have increased. There are many potential reasons to explain this state of facts.¦An important question is to understand how soon the brain may be affected by HIV. Since performing a biopsy in these patients is not an issue, the study of the CSF represents the best available way to look at putative biomarkers of inflammation/neurodegeneration in the CNS. Here, we wanted to examined the putative usefulness of different biomarkers as early indicators of anti-retroviral failure at the level of the CNS. We chose to study the CSF levels of:¦Amyloid-β 1-42 (Aβ42), Tau total (tTau), phosphorylated Tau (pTau), Neopterin and S100-β.¦Indeed, these molecules are representative biomarkers of the major cells of the CNS, i.e. neurons,¦macrophages/microglia and astrocytes.¦To examine how sensitive were these CSF biomarkers to indicate CNS insults caused by HIV, we proposed to take advantage of the MOST (Monotherapy Switzerland/Thailand study) study, recently published in AIDS. Thus, we collaborated with Prof. Pietro Vernazza in St-Gall. In MOST study, monotherapy (MT) consisting in ritonavir-boosted lopinavir (LPV/r) was compared to continuous conventional antiretroviral therapy including several molecules, hereafter referred as CT¦Methods :We tested 61 cerebrospinal fluid (CSF) samples from 52 patients enrolled in MOST, including 34 CSF samples of CT and 27 of MT (mean duration on MT: 47+20 weeks) in patients who maintained full VL suppression in blood (<50cps/ml). Using enzyme-linked immunosorbent assay (ELISA), we determined the CSF concentration of S100-beta (astrocytosis), neopterin (microglia, inflammation), total Tau (tTau), phosphorylated Tau (pTau), and amyloid-beta 1-42 (Abeta), the latter three markers indicating neuronal damages. The CSF samples of 37 HIV-negative patients with Alzheimer dementia (AD) served as controls. Results are expressed in pg/ml and reported as median ± interquartile range. Mann Whitney-U test was used to compare the results of a given biomarker between two groups and the Fisher test to compare frequencies.¦Results: We found a higher concentration of S100-beta (570±1132) and neopterin (2.5±2.9) in the CSF of MT versus CT (0±532, p=0.002 and 1.2±2.5, p=0.058, respectively). A cutoff of 940 pg/ml for S100-beta allowed to discriminate MT (11 above versus 16 below) from CT (1 vs 33, p=0.0003). At a lesser extent, a cutoff of 11 pg/ml for neopterin separated MT (4 above versus 23) from CT (0 vs 34, p=0.034) (Figure).¦In AD, tTau was higher (270±414) and Abeta lower (234±328) than in CT (150±153, p=0.0078, and 466±489, p=0.007, respectively). Such as for CT, Abeta was lower in AD than in MT (390±412, p=0.01). However, contrasting with CT, the levels of tTau were not different between AD and MT (199±177, p=0.11). S100b (173±214; p=0.0006) and neopterin (1.1±0.9; p=0.0014) were lower in AD than MT.¦Conclusions: Despite full VL-suppression in blood, HIV monotherapy is sufficient to trigger inflammation and, especially, astrocytosis. CSF markers of patients on CT have the same profile as reported for healthy subjects, suggesting that CT permits a good control of HIV in the brain. Finally, the levels of tTau, which are relatively similar between AD and MT patients, suggest that neurons are damaged during monotherapy.

Increased eotaxin in tears of patients wearing contact lenses

Résumé Introduction : La conjonctivite giganto-papillaire chez des patients porteurs de lentilles de contact survient lors d'une intolérance et/ou d'une allergie aux lentilles de contact. L'éotaxine est un CC chémokine produisant un puissant effet chémotactique sur les éosinophiles, qui sont impliqués dans les allergies. Le but de cette étude est de mesurer le taux d'éotaxine dans les larmes de patients porteurs de lentilles de contact et de le comparer à celui de sujets normaux. Les taux d'éotaxine sont également corrélés avec le degré de conjonctivite giganto-papillaire. Méthode : Environ 10 Ill de larmes ont été collectés avec une rnicropipette en verre chez 16 patients porteurs de lentilles de contact et chez 10 volontaires normaux. La conjonctivite giganto-papillaire a été évaluée selon une échelle de 0 à 4 en référence à des images photographiques de la paupière supérieure réalisées à la lampe à fente. La concentration de l'éotaxine dans les larmes a été mesurée par un ELISA utilisant un anticorps d'éotaxine de souris dirigé contre l'anticorps humain. Pour l'analyse statistique des résultats, le test de Wilcox/Kruskal-Wallis a été utilisé. Résultats : La concentration moyenne d'éotaxine était de 2698 +233 (SEM) pg/ml chez les patients porteurs de lentilles de contact et de 1498 139 pg/ml chez les sujets normaux. La différence était statistiquement significative avec P = 0.0004. Le score moyen des papilles était de 1.75 ±0.19 chez les patients porteurs de lentilles de contact et de 0.2 +0.13 chez les sujets normaux (P <0.0001). Le grading des papilles a pu être mis en relation avec le taux d'éotaxine dans les larmes (R2- 0.6562 avec P <0.0001). Conclusion : Une augmentation du taux d'éotaxine dans les larmes a été mesurée chez les patients porteurs de lentilles de contact. Les taux d'éotaxine ont été corrélés avec la sévérité de la conjonctivite giganto-papillaire. Ces données suggèrent que l'éotaxine pourrait jouer un rôle important dans la formation des papilles. Abstract : Purpose: Giant papillary conjunctivitis in patients wearing contact lenses occurs after intolerance and/or allergy to contact lenses. Eotaxin is a CC chemokine with a potent and specific chemotactic effect for eosinophils, which are involved in allergies. The purpose of this study is to measure the eotaxin levels in tears of patients wearing contact lenses and in normal subjects. Eotaxin levels were also correlated with the grade of giant papillary conjunctivitis. Methods: Around 10µL of tears were collected with glass capillaries in 16 patients wearing contact lenses and in 10 normal volunteers. Giant papillary conjunctivitis was graded from 0 to 4 by reference to standard slit-lamp photographs of the superior tarsal conjunctiva. Eotaxin concentration in tears was measured by ELSA using mouse anti-human eotaxin monoclonal antibodies. For the statistical analysis of the results, the paired Wilcoxon/Kruskai-Wallis test was used. Results: The mean concentration of eotaxin was 2698 ± 233 (SEM) pg/mL in patients wearing contact lenses and 1498 ± 139 pg/mL normal subjects. The difference was statistically significant (P =0.0004). The mean score of papilla grade was 1.75 ± 0.19 in patients wearing contact lenses and 01 ± 0.13 in normal subjects (P < 0.0001). Papilla grade could be correlated to the eotaxin level in tears (R2 = 0.6562 and P< 0.0001), Conclusion: An increase of eotaxin levels in tears was measured in patients wearing contact lenses. Eotaxin levels correlated with the severity of giant papillary conjunctivitis. These data suggest that eotaxin could play a role in papilla formation.

The fetal membranes of the otter shrews and a synapomorphy for afrotheria.

The otter shrews of mainland Africa are the closest relatives of the Madagascar tenrecs. We sought for similarities in placentation between the two groups and, in a wider context, with other mammals of the Afrotheria clade. Specimens of the Nimba otter shrew (Micropotamogale lamottei) were obtained from the Ivory Coast and examples of the giant otter shrew (Potamogale velox) from the Hill Collection. The Nimba otter shrew has a central haemophagous organ similar to that in tenrecs. The labyrinth of the Nimba otter shrew, however, is endotheliochorial with syncytial trophoblast enclosing the maternal vessels. On the other hand tenrecs have cellular haemomonochorial placentae and an associated spongy zone, which is not present in the Nimba otter shrew. The placenta of the giant otter shrew is also endotheliochorial. The central region of its placenta is particularly interesting, since the juxtafetal portion is clearly a haemophagous region whereas the labyrinth feeding this region is endotheliochorial. Thus there is considerable variation in placental morphology within Tenrecidae. Importantly, however, both otter shrews have a large allantoic sac divided into four intercommunicating lobes by two pairs of septal folds. A similar arrangement has been described for representatives of each of the remaining five orders within Afrotheria. This is significant because previous anatomical studies have failed to establish a single synapomorphy in support of Afrotheria.

Acute ulcerative jejunal diverticulitis: case report of an uncommon entity.

Jejunal diverticulosis is a rare entity with variable clinical and anatomical presentations. Its reported incidence varies from 0.05% to 6%. Although there is no consensus on the management of asymptomatic jejunal diverticular disease, some complications are potentially life threatening and require early surgical treatment. We report a case of an 88-year-old man investigated for acute abdominal pain with a high biological inflammatory syndrome. Inflammation of multiple giant jejunal diverticulum was discovered at abdominal computed tomography (CT). As a result of the clinical and biological signs of early peritonitis, an emergency surgical exploration was performed. The first jejunal loop showed clear signs of jejunal diverticulitis. Primary segmental jejunum resection with end-to-end anastomosis was performed. Histopathology report confirmed an ulcerative jejunal diverticulitis with imminent perforation and acute local peritonitis. The patient made an excellent rapid postoperative recovery. Jejunal diverticulum is rare but may cause serious complications. It should be considered a possible etiology of acute abdomen, especially in elderly patients with unusual symptomatology. Abdominal CT is the diagnostic tool of choice. The best treatment is emergency surgical management.