In vitro investigation of oxide nanoparticle and carbon nanotube toxicity and intracellular accumulation in A549 human pneumocytes

If released in the environment, nanomaterials might be inhaled by populations and cause damage to the deepest regions of the respiratory tract, i.e., the alveolar compartment. To model this situation, we studied the response of A549 human pneumocytes after exposure to aluminium oxide or titanium oxide nanoparticles, and to multi-walled carbon nanotubes. The influence of size, crystalline structure and chemical composition was investigated. After a detailed identification of nanomaterial physico-chemical characteristics, cells were exposed in vitro and viability and intracellular accumulation were assessed. In our conditions, carbon nanotubes were more toxic than metal oxide nanoparticles. Our results confirmed that both nanotubes and nanoparticles are able to rapidly enter into cells, and distribute in the cytoplasm and intracellular vesicles. Among nanoparticles, we demonstrate significant difference in biological response as a function of size, crystalline phase and chemical composition. Their toxicity was globally lower than nanotubes toxicity. Among nanotubes, the length did not influence cytotoxicity, neither the presence of metal catalyst impurities.     

New treatments for cocaine dependence: a focused review

Cocaine, already a significant drug problem in North and South America, has become a more prominent part of the European drug scene. Cocaine dependence has major somatic, psychological, psychiatric, socio-economic, and legal implications. No specific effective pharmacological treatment exists for cocaine dependence. Recent advances in neurobiology have identified various neuronal mechanisms implicated in cocaine addiction and suggested several promising pharmacological approaches. Data were obtained from Medline, EMBASE, and PsycINFO searches of English-language articles published between 1985 and June 2007 using the key words: cocaine, addiction, cocaine dependence, clinical trials, pharmacotherapy(ies) singly and in combination. Large well-controlled studies with appropriate statistical methods were preferred. Pharmacological agents such as GABA agents (topiramate, tiagabine, baclofen and vigabatrin) and agonist replacement agents (modafinil, disulfiram, methylphenidate) seem to be the most promising in treatment of cocaine dependence. The results from trials of first- and second-generation neuroleptics are largely negative. Aripiprazole, a partial dopaminergic agonist that may modulate the serotonergic system, shows some promise. Preliminary results of human studies with anti-cocaine vaccine, N-acetylcysteine, and ondansetron, are promising, as are several compounds in preclinical development. While no medication has received regulatory approval for the treatment of cocaine dependence, several medications marketed for other indications have shown efficacy in clinical trials. An anti-cocaine vaccine and several compounds in preclinical development have also shown promise. Findings from early clinical trials must be confirmed in larger, less selective patient populations.     

Tracking online poker problem gamblers with player account‐based gambling data only

The aim was to develop and validate an instrument to track online problem poker gamblers with player account‐based gambling data (PABGD). We emailed an invitation to all active poker gamblers on the online gambling service provider Winamax. The 14,261 participants completed the Problem Gambling Severity Index (PGSI). PGSI served as a gold standard to track problem gamblers (i.e., PGSI ≥ 5). We used a stepwise logistic regression to build a predictive model of problem gambling with PABGD, and validated it. Of the sample 18% was composed of online poker problem gamblers. The risk factors of problem gambling included in the predictive model were being male, compulsive, younger than 28 years, making a total deposit > 0 euros, having a mean loss per gambling session > 1.7 euros, losing a total of > 45 euros in the last 30 days, having a total stake > 298 euros, having > 60 gambling sessions in the last 30 days, and multi‐tabling. The tracking instrument had a sensitivity of 80%, and a specificity of 50%. The quality of the instrument was good. This study illustrates the feasibility of a method to develop and validate instruments to track online problem gamblers with PABGD only. Copyright © 2016 John Wiley & Sons, Ltd.     

HLA‐G*01:04∼UTR3 Recipient Correlates With Lower Survival and Higher Frequency of Chronic Rejection After Lung Transplantation

Lung transplantation (LTx) is a valid therapeutic option for selected patients with end‐stage lung disease. Soluble HLA‐G (sHLA‐G) has been associated with increased graft survival and decreased rejection episodes in solid organ transplantation. HLA‐G haplotypes named UTRs, defined by SNPs from both the 5′URR and 3′UTR, have been reported to reliably predict sHLA‐G level. The aim of this retrospective study was to determine the impact of HLA‐G alleles and UTR polymorphism from LTx recipients on anti‐HLA allo‐immunization risk, overall survival and chronic rejection (CLAD). HLA‐G SNPs were genotyped in 124 recipients who underwent LTx from 1996 to 2010 in Marseille, 123 healthy individuals and 26 cystic fibrosis patients not requiring LTx. sHLA‐G levels were measured for 38 LTx patients at D0, M3 and M12 and for 123 healthy donors. HLA‐G*01:06～UTR2 was associated with a worse evolution of cystic fibrosis (p = 0.005) but not of long‐term survival post‐LTx. HLA‐G*01:04～UTR3 haplotype was associated with lower levels of sHLA‐G at D0 and M3 (p = 0.03), impaired long‐term survival (p = 0.001), increased CLAD occurrence (p = 0.03) and the production of de novo donor‐specific antibodies (DSA) at M3 (p = 0.01). This study is the first to show the deleterious association of different HLA‐G alleles and UTRs in LTx.     

Pas de chirurgie sans échographie préalable en cas de thrombose veineuse superficielle clinique : à propos d’un cas d’embolie paradoxale grave

Lower limbs superficial venous thrombosis (LLSVT) is usually considered as common and of a benign prognosis. LLSVT can, however, be responsible for major thromboembolic complications: lower limbs deep vein thrombosis (LLDVT) and pulmonary embolism (PE). We report a case of a LLSVT complicated with a massive bilateral PE and an ischemic cerebral stroke, occurring immediately after a varicose vein surgery. Venous ultrasonography of the lower limbs must be systematically performed in case of LLSVT, in order to evaluate the presence of an associated LLDVT. A rigorous diagnostic and therapeutic approach is the only way to optimize the treatment of this disorder, and to avoid the occurrence of dramatic venous thromboembolic complications.     

How to best measure femoral length and lateralisation after total hip arthroplasty on antero-posterior pelvic radiographs

Purpose

Various methods exist for measuring limb length and lateralisation after total hip arthroplasty. Most of them utilise standard anteroposterior (AP) pelvic radiographs, but their results can be affected by patient position during imaging and thus the position of the lower limb on the coronal plane. The aim of this study is to evaluate how commonly used measuring methods of limb lengthening and femoral offset are affected by the position of the lower limb in the coronal plane.

Methods

A standing pelvic AP radiograph post implantation of a right total hip prosthesis was digitised. The right femur and its femoral stem were digitally segmented, such that they could be positioned orthogonal to the pelvis horizontal reference, with 10° of adduction, and with 10° of abduction, with respect to the centre of rotation. Various limb lengths and implant lateralisation were also digitised. We obtained nine x-rays differing one to three variables. Twice four independent surgeons performed three femoral length measurement methods and femoral offset measurement methods. Intra and inter-observer error as well as the effect of the femoral position on the measurements were studied.

Results

With respect to length measurements, the distance between the centre of rotation (C) and the tip of the lesser trochanter (LT) increased by 3 mm per cm of lateralisation. This measurement was not affected by the hip position in abduction or adduction. The distance between the tip of the lesser or greater trochanter (GT) and the horizontal passing through the centre of rotation was strongly affected by the hip position in abduction or adduction. With respect to offset, the distance between the centre of rotation and the greater trochanter (C-GT) was the most consistent and was not affected by variations in lengths or femoral axis. At the level of the lesser trochanter, the distance of the femoral anatomical axis and to Perkin’s line was heavily influenced by the femoral position.

Conclusion

The C-LT distance was consistent in measuring limb length and the C-GT distance was reliable in determining femoral offset regardless of the relative position of the femur.

     

Compensation method for obtaining accurate, sub-micrometer displacement measurements of immersed specimens using electronic speckle interferometry

We proposed and validated a compensation method that accounts for the optical distortion inherent in measuring displacements on specimens immersed in aqueous solution. A spherically-shaped rubber specimen was mounted and pressurized on a custom apparatus, with the resulting surface displacements recorded using electronic speckle pattern interferometry (ESPI). Point-to-point light direction computation is achieved by a ray-tracing strategy coupled with customized B-spline-based analytical representation of the specimen shape. The compensation method reduced the mean magnitude of the displacement error induced by the optical distortion from 35% to 3%, and ESPI displacement measurement repeatability showed a mean variance of 16 nm at the 95% confidence level for immersed specimens. The ESPI interferometer and numerical data analysis procedure presented herein provide reliable, accurate, and repeatable measurement of sub-micrometer deformations obtained from pressurization tests of spherically-shaped specimens immersed in aqueous salt solution. This method can be used to quantify small deformations in biological tissue samples under load, while maintaining the hydration necessary to ensure accurate material property assessment.     

Delayed Correction for Extrapolation in Amblyopia

PurposeIt has been suggested that amblyopes present impaired motion extrapolation mechanisms. In this study, we used the flash grab effect (FGE), the illusory mislocalization of a briefly flashed stimulus in the direction of a reversing moving background, to investigate whether the amblyopic visual system can correct overextrapolation.MethodsThirteen amblyopes and 13 control subjects participated in the experiment. We measured the monocular FGE magnitude for each subject. Two spatial frequency (2 and 8 cycles), two texture configurations (square wave or sine wave), and two speed conditions (270 degrees/s and 67.5 degrees/s) were tested. In addition, control subjects were further tested in reduced luminance conditions.ResultsCompared with controls, amblyopes exhibited a larger FGE magnitude both in their fellow eye (FE) and amblyopic eye (AE). The FGE magnitude of their AE was significantly larger than that of the FE. In a control experiment, we observed that the FGE magnitude increases with the decreasing of the luminance. The FGE magnitude of amblyopes fall into the same range as that of controls under reduced luminance conditions.ConclusionsWe observed a lager FGE in patients with amblyopia, which indicates that the amblyopic visual system does not accurately correct the overextrapolation when a moving object abruptly reverses its direction. This spatiotemporal processing deficit could be ascribed to delayed visual processing in the amblyopic visual system.     

Hemolytic anemia during pegylated IFN-alpha2b plus ribavirin treatment for chronic hepatitis C: ribavirin is not always the culprit.

A 53-year-old woman admitted to our department for histologically proven chronic hepatitis C had previously been treated with pegylated interferon-alpha2b (PEG-IFN) plus ribavirin. Combination therapy had been withdrawn after 5 weeks because of severe anemia (hemoglobin 8.2 g/dl) despite a reduction in ribavirin dose. A second liver biopsy showed moderate chronic hepatitis with portoportal and portocentral bridges (Ishak score: grading 14/18, staging 4-5/6). Consequently, the patient was retreated with 1.5 microg/kg body weight weekly PEG-IFN and 1000 mg/day ribavirin. Ribavirin was withdrawn about 3 months later because of anemia. After 1 month of PEG-IFN alone, hemoglobin had decreased further to reach 7.9 g/dl; consequently IFN was stopped. An elevated reticulocyte count, indirect bilirubin concentration, and lactic dehydrogenase (LDH) concentration, and a positive direct Coombs test (IgG3, C3d also for panagglutinant irregular antibodies on eluate) led us to diagnose autoimmune hemolytic anemia (AHA). The patient received 1 mg/kg body weight/day prednisone, and all parameters normalized within 20 days. This is the first case of IFN-related AHA during PEG-IFN plus ribavirin therapy. Physicians should be aware that PEG-IFN can be the cause of AHA during a ribavirin-containing regimen for chronic hepatitis C.