Plasticity of protein expression during culture of fetal skin cells.

In order to gain insight into the biology of fetal skin during culture, cellular proteins were studied during four culture passages (P00, P01, P04 as well as P10) using high-resolution two-dimensional (2-D) gel electrophoresis and mass spectrometry (MS). Bioinformatic analyses were focused on a region of each gel corresponding to pI between 4 and 8 and M(r) from 8000 to 35 000. In this area, 373 +/- 42 spots were detected (N = 18). Twenty-six spots presented an integrated intensity that increased in the higher passages, whereas five spots showed a progressively lower intensity in subsequent passaging. MS analysis was performed on spots that were unambiguously identified on preparative 2-D gels. Among the 26 spots showing an increased size between P00 and P10, 9 were identified, and corresponded to 3 proteins: (i) peptidyl-prolyl cis-trans isomerase A (P05092; cyclophilin A or cyclosporin A-binding protein), (ii) triosephosphate isomerase (P00938), and (iii) enoyl-CoA hydratase (P30084). Among these nine identified spots, three were absent at P00, but were present at P10. They corresponded to isoforms of peptidyl-prolyl cis-trans isomerase and triosephosphate isomerase, respectively. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses of the acidic isoforms of triosephosphate isomerase showed modifications of cysteine residues to cysteic acid. All these isoforms were clearly present in the skin cells of a 4-year-old child, as well as in skin cells from a 80-year-old man, at P00. These observations probably reflect either an oxidative stress related to cell culture, or, alternatively, maturation, differentiation and the aging of the cells.

Nouveautés dans la stratégie thérapeutique de la diverticulite sigmoïdienne [Current treatment strategies for sigmoid diverticulitis]

Treatment of colonic diverticular disease has evolved over the past years. Most episodes are simple and can be successfully treated with antibiotics alone. For complicated diverticulitis, a strong trend is developing towards less invasive therapies including interventional radiology and laparoscopic lavage in an effort to avoid the morbidity and discomfort of a diverting colostomy. Based on a better understanding of the natural history of the disease, the indication to prophylactic colectomy after a few episodes of simple diverticulitis has been seriously challenged. For those patients who need a colectomy, single port laparoscopy, NOTES and transanal specimen extraction are being proposed. However larger studies are needed to confirm the hypothetical advantages of these evolving techniques.

An EORTC Phase II study of caspofungin as first-line therapy of invasive aspergillosis in haematological patients.

OBJECTIVES: Caspofungin was evaluated as first-line monotherapy of invasive aspergillosis (IA) in patients with haematological malignancies and undergoing autologous transplants. METHODS: Adults with proven or probable IA, defined strictly according to EORTC-MSG criteria, were eligible. Those with possible IA were enrolled, but were not evaluable for efficacy unless upgraded to proven/probable disease within 7 days of registration based on investigations performed within 48 h after enrolment. Caspofungin dosage was 70 mg (day 1) followed by 50 mg/day. The primary endpoint was the proportion of patients with complete or partial response at the end of caspofungin therapy in the modified intention to treat (MITT) group; secondary endpoints were response and survival at day 84 and safety. RESULTS: In the MITT group (n = 61), 75% of patients had cancer not in remission (relapsing or refractory), 85% were neutropenic at enrolment and 49% had a Karnofsky score of < or =50. At end of treatment, 1 and 19 patients had complete and partial response, respectively [success rate 33% (20/61)], 9 (15%) achieved stabilization and 31 (51%) had disease progression. One patient was not evaluable. The 6 and 12 week survival rates were 66% (40/61) and 53% (32/60), respectively. Baseline characteristics associated with survival at day 84 were an underlying disease in remission (not relapsing or refractory) and Karnofsky score. Recovery from neutropenia at the end of treatment was also significantly associated with survival. No serious drug-related adverse events or discontinuations due to drug-related adverse events were observed. CONCLUSIONS: Caspofungin provided an observed response rate compatible with the null hypothesis of a true response rate of < or =35%. Underlying disease-related factors had a major impact on results.

The protective effect of the obesity-associated rs9939609 A variant in fat mass- and obesity-associated gene on depression.

Candidate gene and genome-wide association studies have not identified common variants, which are reliably associated with depression. The recent identification of obesity predisposing genes that are highly expressed in the brain raises the possibility of their genetic contribution to depression. As variation in the intron 1 of the fat mass- and obesity-associated (FTO) gene contributes to polygenic obesity, we assessed the possibility that FTO gene may contribute to depression in a cross-sectional multi-ethnic sample of 6561 depression cases and 21 932 controls selected from the EpiDREAM, INTERHEART, DeCC (depression case-control study) and Cohorte Lausannoise (CoLaus) studies. Major depression was defined according to DSM IV diagnostic criteria. Association analyses were performed under the additive genetic model. A meta-analysis of the four studies showed a significant inverse association between the obesity risk FTO rs9939609 A variant and depression (odds ratio=0.92 (0.89, 0.97), P=3 × 10(-4)) adjusted for age, sex, ethnicity/population structure and body-mass index (BMI) with no significant between-study heterogeneity (I(2)=0%, P=0.63). The FTO rs9939609 A variant was also associated with increased BMI in the four studies (β 0.30 (0.08, 0.51), P=0.0064) adjusted for age, sex and ethnicity/population structure. In conclusion, we provide the first evidence that the FTO rs9939609 A variant may be associated with a lower risk of depression independently of its effect on BMI. This study highlights the potential importance of obesity predisposing genes on depression.

Detection and characterization of hydraulically active fractures in a carbonate aquifer: Results from self-potential, temperature and fluid conductivity logging along a 260-m-deep borehole in the Combioula hydrothermal system in the southwestern Swiss Alps

A geophysical and geochemical study has been conducted in a fractured carbonate aquifer located at Combioula in the southwestern Swiss Alps with the objective to detect and characterize hydraulically active fractures along a 260-m-deep borehole. Hydrochemical analyses, borehole diameter, temperature and fluid electrical conductivity logging data were integrated in order to relate electrokinetic self-potential signals to groundwater flow inside the fracture network. The results show a generally good, albeit locally variable correlation of variations of the self-potential signals with variations in temperature, fluid electrical conductivity and borehole diameter. Together with the hydrochemical evidence, which was found to be critical for the interpretation of the self-potential data, these measurements not only made it possible to detect the hydraulically active fractures but also to characterize them as zones of fluid gain or fluid loss. The results complement the available information from the corresponding litholog and illustrate the potential of electrokinetic self-potential signals in conjunction with temperature, fluid electrical conductivity and hydrochemical analyses for the characterization of fractured aquifers, and thus may offer a perspective for an effective quantitative characterization of this increasingly important class of aquifers and geothermal reservoirs.

Different concentrations of Mg++ ions affect nuclear matrix protein distribution during thermal stabilization of isolated nuclei.

The nuclear matrix, a proteinaceous network believed to be a scaffolding structure determining higher-order organization of chromatin, is usually prepared from intact nuclei by a series of extraction steps. In most cell types investigated the nuclear matrix does not spontaneously resist these treatments but must be stabilized before the application of extracting agents. Incubation of isolated nuclei at 37C or 42C in buffers containing Mg++ has been widely employed as stabilizing agent. We have previously demonstrated that heat treatment induces changes in the distribution of three nuclear scaffold proteins in nuclei prepared in the absence of Mg++ ions. We studied whether different concentrations of Mg++ (2.0-5 mM) affect the spatial distribution of nuclear matrix proteins in nuclei isolated from K562 erythroleukemia cells and stabilized by heat at either 37C or 42C. Five proteins were studied, two of which were RNA metabolism-related proteins (a 105-kD component of splicing complexes and an RNP component), one a 126-kD constituent of a class of nuclear bodies, and two were components of the inner matrix network. The localization of proteins was determined by immunofluorescent staining and confocal scanning laser microscope. Mg++ induced significant changes of antigen distribution even at the lowest concentration employed, and these modifications were enhanced in parallel with increase in the concentration of the divalent cation. The different sensitivity to heat stabilization and Mg++ of these nuclear proteins might reflect a different degree of association with the nuclear scaffold and can be closely related to their functional or structural role.

Prediction of Complications After Pancreaticoduodenectomy: Validation of a Postoperative Complication Score.

OBJECTIVES: Pancreatic surgery remains associated with important morbidity. Efforts are most commonly concentrated on decreasing postoperative morbidity, but early detection of patients at risk could be another valuable strategy. A simple prognostic score has recently been published. This study aimed to validate this score and discuss possible clinical implications. METHODS: From 2000 to 2012, 245 patients underwent a pancreaticoduodenectomy. Complications were graded according to the Dindo-Clavien Classification. The Braga score is based on American Society of Anesthesiologists score, pancreatic texture, Wirsung duct diameter, and blood loss. An overall risk score (0-15) can be calculated for each patient. Score discriminant power was calculated using a receiver operating characteristic curve. RESULTS: Major complications occurred in 31% of patients compared with 17% in Braga's data. Pancreatic texture and blood loss were independently statistically significant for increased morbidity. Areas under the curve were 0.95 and 0.99 for 4-risk categories and for individual scores, respectively. CONCLUSIONS: The Braga score discriminates well between minor and major complications. Our validation suggests that it can be used as a prognostic tool for major complications after pancreaticoduodenectomy. The clinical implications, that is, whether postoperative treatment strategies should be adapted according to the patient's individual risk, remain to be elucidated.

Tabacologie: mise au point 2015 [Smoking cessation: update 2015].

La prévalence mondiale du tabagisme est environ cinq fois plus importante chez les hommes que chez les femmes, toutefois cet écart tend à s'égaliser. En ce qui concerne les conséquences sur la santé du tabagisme, les femmes semblent plus susceptibles que les hommes. Elles sont notamment plus à risque de présenter certains cancers pulmonaires ou de décéder de maladies cardiovasculaires. Si les hommes sont moins enclins à demander de l'aide pour arrêter de fumer, les femmes quant à elles ont moins de succès dans leurs tentatives d'arrêt et les traitements semblent moins efficaces chez ces dernières. Des interventions d'aide à l'arrêt et des mesures de prévention du tabagisme adaptées aux spécificités de genre ont le potentiel d'améliorer la prise en charge des fumeurs et de diminuer les disparités de genre en santé. Smoking remains a major public health problem in Switzerland and is responsible for about 9000 deaths annually. In 2013, a quarter of the Swiss population (15 and over) were smokers and more than half of them wanted to quit smoking. This article provides an update of Swiss clinical practice guidelines published in 2011 and covers several new features, including views regarding smoking reduction, gradual quitting, use of nicotine replacement therapy for a short period prior to quitting, nicotine mouth spray marketing and the reimbursement of varenicline and bupropion treatments (under certain conditions) by basic health insurance. An algorithm summarizes the different stages of management of patients who smoke.

Services "amis des jeunes": promouvoir des soins adaptés aux adolescents [Youth friendly health services: how to promote quality health care for adolescents].

Beaucoup de jeunes éprouvent des difficultés à demander une aide médicale et psychosociale alors qu'ils en auraient bien besoin. Cela est lié au processus d'autonomisation propre à cette période de la vie : les adolescents souhaitent résoudre leurs problèmes eux-mêmes. Pour améliorer la qualité des soins aux jeunes, l'Organisation mondiale de la santé, avec l'UNICEF et d'autres organismes, a développé le concept de youth friendly health services ; services amis des jeunes. Ce concept repose sur plusieurs principes, comme l'accessibilité, la flexibilité, une formation spécifique du personnel, le respect de la neutralité et de la confidentialité, compétences communicationnelles, etc. L'application de cette approche ne se limite pas aux centres spécialisés en médecine de l'adolescence, mais devra être progressivement implantée dans toutes les structures de soins accueillant des jeunes. Many young people have difficulties requesting medical or psychosocial support, although some badly need it. This difficulty is related to the fact that, as part of their search for autonomy, young people prefer to solve their problems by themselves. To improve the quality of care, the World Health Organization, UNICEF and allied organizations have developed the concept of "Youth friendly health services". This concept includes policies and strategies to improve the accessibility and flexibility, staff's competence and communication skills, etc. Such an approach should not be limited to specialized centers for adolescent health. It should be adopted by all health care institutions dealing with young people.