Phase 1 study of the immunotoxin LMB-100 in patients with mesothelioma and other solid tumors expressing mesothelin.

Background: LMB-100 is an antibody-toxin conjugate with an antimesothelin Fab linked to a 24-kilodalton portion of Pseudomonas exotoxin A with mutations that decrease immunogenicity. The objective of the current first-in-human phase 1 study was to determine the maximum tolerated dose (MTD) and safety in patients with advanced solid tumors expressing mesothelin.

Methods: Cohorts of 1 to 7 patients received intravenous LMB-100 at 7 dose levels from 40 µg/kg to 250 µg/kg intravenously on days 1, 3, and 5 of a 21-day cycle.

Modelling daily and hourly loads of pharmaceuticals in urban wastewater.

Pharmaceuticals are known contaminants of the environment. Assessing and managing the risk associated to this contamination has become an important field of study in environmental sciences. Accurately sampling and measuring pharmaceuticals concentrations in wastewater or in the environment is still costly and difficult.

Lateral Antebrachial Cutaneous Nerve as Autologous Graft for Mini-Invasive Corneal Neurotization (MICORNE).

Purpose: We describe the first case of a novel surgical technique of mini-invasive corneal neurotization (MICORNE) using the lateral antebrachial cutaneous nerve as a graft nerve and the contralateral supraorbital nerve as a donor nerve in a herpetic patient with a neurotrophic keratopathy (NK).

Methods: A MICORNE procedure was performed in a 32-year-old man with a 5-year history of herpes simplex virus (HSV)-related NK in the right eye (RE). Visual acuity and corneal sensation were assessed over 9 months of follow-up.

Inhibitors of retrograde trafficking active against ricin and Shiga toxins also protect cells from several viruses, Leishmania and Chlamydiales.

Medical countermeasures to treat biothreat agent infections require broad-spectrum therapeutics that do not induce agent resistance. A cell-based high-throughput screen (HTS) against ricin toxin combined with hit optimization allowed selection of a family of compounds that meet these requirements. The hit compound Retro-2 and its derivatives have been demonstrated to be safe in vivo in mice even at high doses.

Identification of Vaccine-Altered Circulating B Cell Phenotypes Using Mass Cytometry and a Two-Step Clustering Analysis.

Broadening our understanding of the abundance and phenotype of B cell subsets that are induced or perturbed by exogenous Ags will improve the vaccine evaluation process. Mass cytometry (CyTOF) is being used to increase the number of markers that can be investigated in single cells, and therefore characterize cell phenotype at an unprecedented level. We designed a panel of CyTOF Abs to compare the B cell response in cynomolgus macaques at baseline, and 8 and 28 d after the second homologous immunization with modified vaccinia virus Ankara.

Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort.

Background: Chronic inflammation and oxidative stress are thought to be involved in colorectal cancer development. These processes may contribute to leakage of bacterial products, such as lipopolysaccharide (LPS) and flagellin, across the gut barrier. The objective of this study, nested within a prospective cohort, was to examine associations between circulating LPS and flagellin serum antibody levels and colorectal cancer risk.

Comparative Short-term Benefits of Laparoscopic Liver Resection: 9000 Cases and Climbing.

Objective: To perform a systematic review of worldwide literature on laparoscopic liver resections (LLR) and compare short-term outcomes against open liver resections (OLR) by meta-analyses.

Summary Background Data: There are no updated pooled data since 2009 about the current status and short-term outcomes of LLR worldwide.

Patients And Methods: All English language publications on LLR were screened.

Pearls and pitfalls in managing right heart failure in cardiac surgery.

Purpose Of Review: To review the recent insights in the evaluation and management of perioperative (RHF).

Recent Findings: Recent studies highlight the potential role of myocardial deformation imaging in the evaluation of patients at risk of postoperative RHF. There is also a growing interest to study the value of load-adaptation indices of the right heart in the setting of pulmonary hypertension or left ventricular assist device implantation.

Adolescent Repeated Alcohol Intoxication as a Predictor of Young Adulthood Alcohol Abuse: The Role of Socioeconomic Context.

Aims: Trajectories of alcohol abuse from adolescence onwards are not well known. We examined the relationship between repeated alcohol intoxication in adolescence and later alcohol abuse, testing whether this association varies depending on individuals' socioeconomic context.

Methods: Study participants (n = 674, age 22-35 years in 2009) belong to the French TEMPO cohort study; their parents also participate in an epidemiological study-the GAZEL cohort.

Genotype-phenotype correlation and course of transthyretin familial amyloid polyneuropathies in France.

Objective: To compare the natural history of familial transthyretin amyloid polyneuropathies (FAP) due to the Val30Met, Ser77Tyr, and Ile107Val mutations in France with the classical Portuguese Val30Met FAP.

Methods: We compared 84 French patients with a control group of 110 Portuguese patients carrying the Val30Met mutation also living in France, all referred to and followed at the French National FAP Reference Center from 1988 to 2010. Clinical examination, functional and walking disability scores, nerve conduction studies, and muscle biopsies are reported.

Truncating Mutations of MAGEL2, a Gene within the Prader-Willi Locus, Are Responsible for Severe Arthrogryposis.

Arthrogryposis multiplex congenita (AMC) is characterized by the presence of multiple joint contractures resulting from reduced or absent fetal movement. Here, we report two unrelated families affected by lethal AMC. By genetic mapping and whole-exome sequencing in a multiplex family, a heterozygous truncating MAGEL2 mutation leading to frameshift and a premature stop codon (c.

Late outcomes after arterial switch operation for Taussig-Bing anomaly.

Objective: To assess the long-term results of the arterial switch operation (ASO) for Taussig-Bing Anomaly (TBA) and identify risk factors affecting outcomes.

Methods: Retrospective review and late follow-up was performed for all TBA patients from 1997 to 2010 (follow-up >3 years). Selection criteria included the absence of mitro-pulmonary continuity.

Neural and cognitive correlates of the common and specific variance across externalizing problems in young adolescence.

Longitudinal and family-based research suggests that conduct disorder, substance misuse, and ADHD involve both unique forms of dysfunction as well as more specific dysfunctions unique to each condition. Using direct measures of brain function, this study also found evidence in both unique and disorder-specific perturbations.

Europium-quantum dot nanobioconjugates as luminescent probes for time-gated biosensing.

Nanobioconjugates have been synthesized using cadmium selenide quantum dots (QDs), europium complexes (EuCs), and biotin. In those conjugates, long-lived photoluminescence (PL) is provided by the europium complexes, which efficiently transfer energy via Förster resonance energy transfer (FRET) to the QDs in close spatial proximity. As a result, the conjugates have a PL emission spectrum characteristic for QDs combined with the long PL decay time characteristic for EuCs.

Importance of conserving middle hepatic vein distal branches for homogeneous regeneration of the left liver after right hepatectomy.

Background: Liver regeneration enables repeat surgical procedures to achieve a potential cure in liver cancer patients. However, data regarding segmental regeneration and liver anatomy after liver resection are scarce. This study examined left liver regeneration after right hepatectomy and the impact of hepatic venous drainage on the regeneration of the paramedian sector (Couinaud's segment IV).

Subjective age and social-cognitive determinants of physical activity in active older adults.

Objective: The purpose of the current study was to examine the mediating role of self-efficacy in the relationship between subjective age and intention to engage in physical activity (PA) among active older adults. It was expected that subjective age would be positively related to PA intention because it is positively associated with self-efficacy.

Method: A cross-sectional study was conducted with 170 older adults age 60-80 years (M = 66.

Activation of the phosphatidylinositol 3'-kinase/AKT pathway in neuroblastoma and its regulation by thioredoxin 1.

Neuroblastoma is a malignant pediatric tumor with poor survival. The phosphatidylinositol 3'-kinase/AKT pathway is a crucial regulator of cellular processes including apoptosis. Thioredoxin 1, an inhibitor of tumor-suppressor phosphatase and tensin homolog, is overexpressed in many tumors.

A behavioral ecology approach to traffic accidents: interspecific variation in causes of traffic casualties among birds.

Birds and other animals are frequently killed by cars, causing the death of many million individuals per year. Why some species are killed more often than others has never been investigated. In this work hypothesized that risk taking behavior may affect the probability of certain kinds of individuals being killed disproportionately often.

Ontogeny of Drosophila melanogaster female sex-appeal and cuticular hydrocarbons.

The chemical communication system in Drosophila melanogaster Meigen, 1830 plays a major role in courtship and consists of the male-specific cis-Vaccenyl acetate and sex-specific contact pheromones, cuticular hydrocarbons (CHC), which build up during ontogeny (first 4 days). They replace longer CHCs, common to both sexes and present only after the imaginal eclosion. A detailed quantitative description of the evolution of cuticular unsaturated hydrocarbons with age is presented here for males and females of different D.

Liver diseases related to MDR3 (ABCB4) gene deficiency.

Class III multidrug resistance P-glycoproteins, mdr2 in mice and MDR3 in human, are canalicular phospholipid translocators involved in biliary phospholipid (phosphatidylcholine) excretion.The role of a MDR3 (ABCB4) gene defect in liver disease has been initially proven in a subtype of progressive familial intrahepatic cholestasis called PFIC3, a severe pediatric liver disease that may require liver transplantation.Several MDR3 mutations have been identified in children with PFIC3 and are associated to low level of phospholipids in bile leading to high biliary cholesterol saturation index.

Psoralen-induced DNA adducts are substrates for the base excision repair pathway in human cells.

Interstrand cross-link (ICL) is a covalent modification of both strands of DNA, which prevents DNA strand separation during transcription and replication. Upon photoactivation 8-methoxypsoralen (8-MOP+UVA) alkylates both strands of DNA duplex at the 5,6-double bond of thymidines, generating monoadducts (MAs) and ICLs. It was thought that bulky DNA lesions such as MAs are eliminated only in the nucleotide excision repair pathway.

Enhanced activity of the myocardial Na+/H+ exchanger contributes to left ventricular hypertrophy in the Goto-Kakizaki rat model of type 2 diabetes: critical role of Akt.

Aims/hypothesis: Diabetes mellitus is a strong risk factor for the development of heart failure, and left ventricular (LV) hypertrophy has been detected in a significant proportion of diabetic patients. Because several studies have suggested that the Na(+)/H(+) exchanger (NHE1) plays a part in the molecular mechanisms involved in cardiac hypertrophy, we investigated its activity and its role in LV myocytes from the Goto-Kakizaki (GK) rat model of type 2 diabetes.

Materials And Methods: Fluorometric measurements were used to assess sarcolemmal NHE1 activity in isolated myocytes.

Prenatal molecular diagnosis of inherited cholestatic diseases.

Objectives: Progressive familial intrahepatic cholestasis (PFIC) and to a lesser extent, Alagille syndrome, often lead to end-stage liver disease during childhood. We report our experience of DNA-based prenatal diagnosis of PFIC1-3 and Alagille syndrome.

Patients And Methods: Four molecular antenatal diagnoses were performed in 3 PFIC families and 17 in 11 Alagille syndrome families.