Evidence for enhanced neurobehavioral vulnerability to nicotine during periadolescence in rats

Epidemiological studies indicate that there is an increased likelihood for the development of nicotine addiction when cigarette smoking starts early during adolescence. These observations suggest that adolescence could be a “critical ” ontogenetic period, during which drugs of abuse have distinct effects responsible for the development of dependence later in life. We compared the long-term behavioral and molecular effects of repeated nicotine treatment during either periadolescence or postadolescence in rats. It was found that exposure to nicotine during periadolescence, but not a similar exposure in the postadolescent period, increased the intravenous self-administration of nicotine and the expression of distinct subunits of the ligand-gated acetylcholine receptor in adult animals. Both these changes indicated an increased sensitivity to the addictive properties of nicotine. In conclusion, adolescence seems to be a critical developmental period, characterized by enhanced neurobehavioral vulnerability to nicotine. Key words: nicotine; adolescence; intravenous; self-administration; acetylcholine receptor; PC

Hum. Reprod. Advance

what is known already: A global decrease in human sperm quality is still debated as geographical differences have been shown, and many criticisms have risen concerning studies with small and biased study populations or inappropriate statistical methodology. However, growing biological, toxicological, experimental and human exposure data support the endocrine disruptors' hypothesis assuming that fetal exposure to endocrine disruptors could impair reproductive outcomes. study design, size, duration: This was a retrospective and descriptive study using data registered by Fivnat, the professional association in charge of statistics for ART in France during the 1989-2005 study period. Data were provided by 126 main ART centres over the whole metropolitan territory. The source population included 154 712 men, aged 18-70, who were partners of couples undergoing their first ART cycle and for whom semen quality indicators (concentration, total motility and percentage of morphologically normal forms), measured on fresh ejaculated semen, were available. participants/materials, setting, methods: The study population was 26 609 partners of women who had both tubes either absent or blocked. The temporal trends for each indicator of semen quality were modelled using a generalized additive model that allowed for nonlinear relationships between variables and were adjusted for season and age. In-depth sensitivity analyses included the reiteration of the analysis on data from a second spermiogram available for each man and on another subsample of men diagnosed as fertile. Variables such as centre, technique (standard in vitro fertilization or intra-cytoplasmic sperm injection) and an interaction factor between technique and time were also included in the model. main results and the role of chance: There was a significant and continuous decrease in sperm concentration of 32.2% [26.3-36.3] during the study period. Projections indicate that concentration for a 35-year-old man went from an average of 73.6 million/ml [69.0-78.4] in 1989 to 49.9 million/ml [43.5-54.7] in 2005. A significant, but not quantifiable, decrease in the percentage of sperm with morphologically normal forms along the 17-year period was also observed. There was no global trend but a slight, significant increase in total motility between 1994 and 1998 was observed. The results were robust after sensitivity analysis. limitations, reasons for caution: Socioeconomic status could not be controlled for. Despite universal access to medical services in France, couples undergoing ART are expected to have a higher educational level on average compared with those of the general population. Therefore, the real values in the general population could be slightly lower than those presented and the decrease possibly stronger, as the population study is less likely to smoke or be overweight, two factors known to impair semen quality. wider implications of the findings: As the men were selected without a priori knowledge regarding their semen quality characteristics, the results are expected to be close to the values in the general French population. The very large sample size and the robustness of the results confer great statistical power and credibility to the results. To our knowledge, it is the first study concluding a severe and general decrease in sperm concentration and morphology at the scale of a whole country over a substantial period. This constitutes a serious public health warning. The link with the environment particularly needs to be determined

The prognosis of streptococcal prosthetic bone and joint infections depends on surgical management-A multicenter retrospective study

BACKGROUND: The optimal treatment of streptococcal prosthetic joint infections (PJIs) is unclear. METHODS: A cohort of streptococcal PJIs was reviewed retrospectively in seven reference centers for the management of complex bone and joint infections, covering the period January 1, 2010 to December 31, 2012. RESULTS: Seventy patients with monomicrobial infections were included: 47 had infections of total hip arthroplasty and 23 had infections of total knee arthroplasty. The median age was 77 years (interquartile range (IQR) 69-83 years), the median Charlson comorbidity score was 4 (IQR 3-6), and 15.6% (n=11) had diabetes. The most commonly identified streptococcal species were Streptococcus agalactiae and Streptococcus dysgalactiae (38.6% (n=27) and 17.1% (n=12), respectively). Debridement, antibiotics and implant retention (DAIR) was performed after a median time of 7 days (IQR 3-8 days), with polyethylene exchange (PE) in 21% of cases. After a minimum follow-up of 2 years, 27% of patients had relapsed, corresponding to 51.4% of DAIR treatment cases and 0% of one-stage (n=15) or two-stage (n=17) exchange strategy cases. Rifampicin or levofloxacin in combination therapy was not associated with a better outcome (adjusted p= 0.99). S. agalactiae species and DAIR treatment were associated with a higher risk of failure. On multivariate analysis, only DAIR treatment and S. agalactiae were independent factors of relapse. Compared to DAIR without PE, DAIR with PE was only associated with a trend towards a benefit (odds ratio 0.33, 95% confidence interval 0.06-1.96; adjusted p= 0.44). CONCLUSIONS: Streptococcal PJIs managed with DAIR have a poor prognosis and S. agalactiae seems to be an independent factor of treatment failure

Radiographic Outcomes of Adult Spinal Deformity Correction : A Critical Analysis of Variability and Failures Across Deformity Patterns

International audienceStudy Design: Multicenter, prospective, consecutive, surgical case series from the International Spine Study Group.Objectives: To evaluate the effectiveness of surgical treatment in restoring spinopelvic (SP) alignment.Summary of Background Data: Pain and disability in the setting of adult spinal deformity have been correlated with global coronal alignment (GCA), sagittal vertical axis (SVA), pelvic incidence/lumbar lordosis mismatch (PI-LL), and pelvic tilt (PT). One of the maingoals of surgery for adult spinal deformity is to correct these parameters to restore harmonious SP alignment.Methods: Inclusion criteria were operative patients (age greater than 18 years) with baseline (BL) and 1-year full-length X-rays. Thoracic and thoracolumbar Cobb angle and previous mentioned parameters were calculated. Each parameter at BL and 1 year was categorized as either pathological or normal. Pathologic limits were: Cobb greater than 30 , GCA greater than 40 mm, SVA greater than 40 mm, PI-LL greater than 10 , and PT greater than 20 . According to thresholds, corrected or worsened alignment groups of patients were identified and overall radiographic effectiveness of procedure was evaluated by combining the results from the coronal and sagittal planes

Un diagnostic fiable de fibrose hépatique ou de cirrhose peut être fait avec un seul test sanguin et sans biopsie nécessaire

Date du colloque&nbsp;: 09/2008</p

FibroMeters: a family of blood tests for liver fibrosis with high diagnostic performance and applicability in clinical practice

International audienc

Safe lipid nanocapsule-based gel technology to target lymph nodes and combat mediastinal metastases from an orthotopic non-small-cell lung cancer model in SCID-CB17 mice

The purpose of this study is the assessment of gel technology based on a lauroyl derivative of gemcitabine encapsulated in lipid nanocapsules delivered subcutaneously or intravenously after dilution to target lymph nodes, induce less systemic toxicity and combat mediastinal metastases from an orthotopic model of human, squamous, non-small-cell lung cancer Ma44-3 cells implanted in severe combined immunodeficiency mice. The gel technology mainly targeted lymph nodes as revealed by the biodistribution study. Moreover, the gel technology induced no significant myelosuppression (platelet count) in comparison with the control saline group, unlike the conventional intravenous gemcitabine hydrochloride treated group (P &lt; 0.05). Besides, the gel technology, delivered subcutaneously twice a week, was able to combat locally mediastinal metastases from the orthotopic lung tumor and to significantly delay death (P &lt; 0.05) as was the diluted gel technology delivered intravenously three times a week

A single blood test adjusted for different liver fibrosis targets improves fibrosis staging and especially cirrhosis diagnosis

Fibrosis blood tests are usually developed using significant fibrosis, which is a unique diagnostic target; however, these tests are employed for other diagnostic targets, such as cirrhosis. We aimed to improve fibrosis staging accuracy by simultaneously targeting biomarkers for several diagnostic targets. A total of 3,809 patients were included, comprising 1,012 individuals with chronic hepatitis C (CHC) into a derivation population and 2,797 individuals into validation populations of different etiologies (CHC, chronic hepatitis B, human immunodeficiency virus/CHC, nonalcoholic fatty liver disease, alcohol) using Metavir fibrosis stages as reference. FibroMeter biomarkers were targeted for different fibrosis-stage combinations into classical scores by logistic regression. Independent scores were combined into a single score reflecting Metavir stages by linear regression and called Multi-FibroMeter Version Second Generation (V2G). The primary objective was to combine the advantages of a test targeted for significant fibrosis (FibroMeter) with those of a test targeted for cirrhosis (CirrhoMeter). In the derivation CHC population, we first compared Multi-FibroMeter to FibroMeter and observed significant increases in the cirrhosis area under the receiver operating characteristic curve (AUROC), Obuchowski index (reflecting all fibrosis-stage AUROCs), and classification metric (six classes expressed as a correctly classified percentage) and a nonsignificant increase in significant fibrosis AUROC. Thereafter, we compared it to CirroMeter and observed a nonsignificant increase in the cirrhosis AUROC. In all 3,809 patients, respective accuracies for Multi-FibroMeter and FibroMeter were the following: cirrhosis AUROC, 0.906 versus 0.878 ( 0.001; versus CirroMeter, 0.897, 0.014); Obuchowski index, 0.795 versus 0.791 ( 0.059); classification, 86.0% versus 82.1% ( 0.001); significant fibrosis AUROC, 0.833 versus 0.832 ( 0.366). Multi-FibroMeter had the highest correlation with the area of portoseptal fibrosis and the highest reproducibility over time. Correct classification rates of Multi-FibroMeter with hyaluronate (V2G, 86.0%) or without (V3G, 86.1%) did not differ ( 0.938). Multitargeting biomarkers significantly improves fibrosis staging and especially cirrhosis diagnosis compared to classical single-targeted blood tests. ( 2018;2:455-466)

Practical diagnosis of cirrhosis in non-alcoholic fatty liver disease using currently available non-invasive fibrosis tests

Unlike for advanced liver fibrosis, the practical rules for the early non-invasive diagnosis of cirrhosis in NAFLD remain not well defined. Here, we report the derivation and validation of a stepwise diagnostic algorithm in 1568 patients with NAFLD and liver biopsy coming from four independent cohorts. The study algorithm, using first the elastography-based tests Agile3+ and Agile4 and then the specialized blood tests FibroMeterV3G and CirrhoMeterV3G, provides stratification in four groups, the last of which is enriched in cirrhosis (71% prevalence in the validation set). A risk prediction chart is also derived to allow estimation of the individual probability of cirrhosis. The predicted risk shows excellent calibration in the validation set, and mean difference with perfect prediction is only −2.9%. These tools improve the personalized non-invasive diagnosis of cirrhosis in NAFLD