Reducing the Flexibility of Type II Dehydroquinase for Inhibition: A Fragment-Based Approach and Molecular Dynamics Study.

A multidisciplinary approach was used to identify and optimize a quinazolinedione-based ligand that would decrease the flexibility of the substrate-covering loop (catalytic loop) of the type II dehydroquinase from Helicobacter pylori. This enzyme, which is essential for the survival of this bacterium, is involved in the biosynthesis of aromatic amino acids. A computer-aided fragment-based protocol (ALTA) was first used to identify the aromatic fragments able to block the interface pocket that separates two neighboring enzyme subunits and is located at the active site entrance.

Short and long-term experiments on the effect of sulphide on microalgae cultivation in tertiary sewage treatment.

Microalgae cultivation appears to be a promising technology for treating nutrient-rich effluents from anaerobic membrane bioreactors, as microalgae are able to consume nutrients from sewage without an organic carbon source, although the sulphide formed during the anaerobic treatment does have negative effects on microalgae growth. Short and long-term experiments were carried out on the effects of sulphide on a mixed microalgae culture. The short-term experiments showed that the oxygen production rate (OPR) dropped as sulphide concentration increased: a concentration of 5mgSL reduced OPR by 43%, while a concentration of 50mgSL came close to completely inhibiting microalgae growth.

Identification of STAC3 variants in non-Native American families with overlapping features of Carey-Fineman-Ziter syndrome and Moebius syndrome.

Horstick et al. (2013) previously reported a homozygous p.Trp284Ser variant in STAC3 as the cause of Native American myopathy (NAM) in 5 Lumbee Native American families with congenital hypotonia and weakness, cleft palate, short stature, ptosis, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia (MH).

Long-Term Follow-up Consultation After Childhood Cancer in the Rhône-Alpes Region of France: Feedback From Adult Survivors and Their General Practitioners.

Purpose: We evaluated the satisfaction of adult survivors of childhood cancers and their general practitioners (GP) after a long-term consultation.

Methods: The first Long-term Follow-up Study in Oncology (SALTO1) is a prospective cohort study of survivors of childhood cancers (except leukemia) diagnosed between 1987 and 1992 in the Rhône-Alpes and Auvergne regions of France. Of the 481 patients eligible for the study, 150 participated in a long-term consultation with a pediatric oncologist and an internist, after which survivors and their GPs received long-term plans and recommendations based on consultation findings.

Open-Label, Phase II Study to Assess the Efficacy and Safety of Canakinumab Treatment in Active Hyperimmunoglobulinemia D With Periodic Fever Syndrome.

Objective: To evaluate the efficacy and safety of canakinumab treatment in active hyperimmunoglobulinemia D with periodic fever syndrome (HIDS).

Methods: This was a 3-part open-label study with an initial 6-month treatment period in which patients with HIDS (n = 9) received canakinumab subcutaneously at a dose of 300 mg (or 4 mg/kg for those weighing ≤40 kg) every 6 weeks (period 1 [P1]), followed by a 6-month withdrawal period (period 2 [P2]), and then a 24-month extension treatment period with canakinumab at the same dose (period 3 [P3]). The primary end point was reduction in the frequency of attacks during treatment periods as compared to the historical period (HP; defined as the period in which patients did not receive drugs other than nonsteroidal antiinflammatory drugs and/or steroids).

Prenatal Nonvisualization of the Gallbladder: A Diagnostic and Prognostic Dilemma.

Introduction: Nonvisualization of the fetal gallbladder has been associated with benign conditions such as isolated gallbladder agenesis or severe diseases such as biliary atresia (BA). Recently, gamma-glutamyl transpeptidase (GGTP) fetal blood levels were reported as useful after 22 weeks.

Objective: To determine the contribution of fetal blood GGTP levels after 22 weeks, based on 2 cases.

Δ133p53 represses p53-inducible senescence genes and enhances the generation of human induced pluripotent stem cells.

p53 functions to induce cellular senescence, which is incompatible with self-renewal of pluripotent stem cells such as induced pluripotent stem cells (iPSC) and embryonic stem cells (ESC). However, p53 also has essential roles in these cells through DNA damage repair for maintaining genomic integrity and high sensitivity to apoptosis for eliminating severely damaged cells. We hypothesized that Δ133p53, a physiological inhibitory p53 isoform, is involved in the balanced regulation of self-renewing capacity, DNA damage repair and apoptosis.

Contribution of genetic factors to platinum-based chemotherapy sensitivity and prognosis of non-small cell lung cancer.

Although platinum-based chemotherapy remains the standard treatment for advanced NSCLC patients, clinical outcomes are poor and most patients develop high-grade toxicities. Genetic factors, such as single nucleotide polymorphisms (SNPs) involved in platinum pharmacodynamics, metabolism and mechanism of action, may account for inter-individual differences shown in effectiveness and toxicity. Polymorphisms in genes involved in DNA repair and others such as PI3K/PTEN/AKT and TGF-β pathways have been demonstrated to be associated with response, survival and toxicity in advanced NSCLC patients treated with platinum-based chemotherapy.

Drug Discovery Testing Compounds in Patient Samples by Automated Flow Cytometry.

Functional ex vivo assays that predict a patient's clinical response to anticancer drugs for guiding cancer treatment have long been a goal, but few have yet proved to be reliable. To address this, we have developed an automated flow cytometry platform for drug screening that evaluates multiple endpoints with a robust data analysis system that can capture the complex mechanisms of action across different compounds. This system, called PharmaFlow, is used to test peripheral blood or bone marrow samples from patients diagnosed with hematological malignancies.

Perinatal outcomes in children born after fresh or frozen embryo transfer: a Catalan cohort study based on 14,262 newborns.

Objective: To ascertain whether perinatal outcomes are affected by vitrification and/or controlled ovarian hyperstimulation (COH).

Design: Register-based cohort study.

Setting: Not applicable.

Unilateral Salpingectomy and Methotrexate Are Associated With a Similar Recurrence Rate of Ectopic Pregnancy in Patients Undergoing In Vitro Fertilization.

Study Objective: To determine whether different treatment approaches of ectopic pregnancy (EP), particularly unilateral salpingectomy and methotrexate, affect its recurrence rate in patients undergoing in vitro fertilization (IVF).

Design: A retrospective cohort study (Canadian Task Force classification II-2).

Setting: An academic medical center.

Pharmacokinetic Analysis and in Vivo Antitumor Efficacy of Taccalonolides AF and AJ.

The taccalonolides are microtubule stabilizers that covalently bind tubulin and circumvent clinically relevant forms of resistance to other drugs of this class. Efforts are under way to identify a taccalonolide with optimal properties for clinical development. The structurally similar taccalonolides AF and AJ have comparable microtubule-stabilizing activities in vitro, but taccalonolide AF has excellent in vivo antitumor efficacy when administered systemically, while taccalonolide AJ does not elicit this activity even at maximum tolerated dose.

Antibody 10-1074 suppresses viremia in HIV-1-infected individuals.

Monoclonal antibody 10-1074 targets the V3 glycan supersite on the HIV-1 envelope (Env) protein. It is among the most potent anti-HIV-1 neutralizing antibodies isolated so far. Here we report on its safety and activity in 33 individuals who received a single intravenous infusion of the antibody.

Morphologic grading of euploid blastocysts influences implantation and ongoing pregnancy rates.

Objective: To determine whether blastocyst grading can predict pregnancy outcomes in the frozen-thawed embryo transfer (FET) of euploid blastocysts.

Design: Retrospective cohort study.

Setting: Academic medical center.

Metals as chemical tracers to discriminate ecological populations of threatened Franciscana dolphins (Pontoporia blainvillei) from Argentina.

Franciscana dolphins are the most impacted small cetacean in the Southwestern Atlantic Ocean, classified as Vulnerable A3d by IUCN. Essential (Fe, Mo, Mn, Cr, Ni, Co) and non-essential (Ag, Pb, Sn) trace elements (TEs) were measured in liver, kidney, and brain samples of by-catch Franciscana dolphins that were living in estuarine (n = 21) and marine (n = 21) habitats (1) to assess whether TEs posed a threat and (2) to evaluate the suitability of TEs for discriminating ecological populations of this species in Argentinean waters. Essential TEs showed little variation in tissues from both groups in agreement with levels reported for other cetaceans and suggesting that these concentrations correspond to normal physiological levels.

Liquid biopsy in early stage lung cancer.

Lung cancer is the leading cause of cancer-associated deaths worldwide. Surgery is the standard treatment for early-stage non-small cell lung cancer (NSCLC). However, 30% to 80% of these patients will die within 5 yearS of diagnosis.

Methylation analyses in liquid biopsy.

Lung cancer is the leading cause of cancer-related deaths worldwide. Recent implementation of low-dose computed tomography (LDCT) screening is predicted to lead to diagnosis of lung cancer at an earlier stage, with survival benefit. However, there is still a pressing need for biomarkers that will identify individuals eligible for screening, as well as improve the diagnostic accuracy of LDCT.

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016.

[This corrects the article DOI: 10.1186/s13054-016-1208-6.].

Excerpts from the 1st international NTNU symposium on current and future clinical biomarkers of cancer: innovation and implementation, June 16th and 17th 2016, Trondheim, Norway.

The goal of biomarker research is to identify clinically valid markers. Despite decades of research there has been disappointingly few molecules or techniques that are in use today. The "1st International NTNU Symposium on Current and Future Clinical Biomarkers of Cancer: Innovation and Implementation", was held June 16th and 17th 2016, at the Knowledge Center of the St.

A Two-Gene Prognostic Classifier for Early-Stage Lung Squamous Cell Carcinoma in Multiple Large-Scale and Geographically Diverse Cohorts.

Introduction: There are no validated molecular methods that prospectively identify patients with surgically resected lung squamous cell carcinoma (SCC) at high risk for recurrence. By focusing on the expression of genes with known functions in development of lung SCC and prognosis, we sought to develop a robust prognostic classifier of early-stage lung SCC.

Methods: The expression of 253 genes selected by literature search was evaluated in microarrays from 107 stage I/II tumors.