Metabolomics Simultaneously Derives Benchmark Dose Estimates and Discovers Metabolic Biotransformations in a Rat Bioassay.

Benchmark dose (BMD) modeling estimates the dose of a chemical that causes a perturbation from baseline. Transcriptional BMDs have been shown to be relatively consistent with apical end point BMDs, opening the door to using molecular BMDs to derive human health-based guidance values for chemical exposure. Metabolomics measures the responses of small-molecule endogenous metabolites to chemical exposure, complementing transcriptomics by characterizing downstream molecular phenotypes that are more closely associated with apical end points.

The impact of mental health on health-related quality of life in patients with NF2-related Schwannomatosis.

NF2-related schwannomatosis (NF2-SWN) is a rare genetic disorder and is associated with progressive morbidities. This study aimed to investigate the relationship between NF2-SWN disease severity, health-related Quality of Life (QoL), and mental health aspects of patients. Standardised questionnaires assessing mental health problems (symptoms of depression, anxiety, and somatic burden), psychological factors (resilience, loneliness, and personality functioning), and health-related QoL were administered to 97 patients with NF2-SWN.

The German version of the neurofibromatosis 2 impact on quality of life questionnaire correlates with severity of depression and physician-reported disease severity.

Background: Neurofibromatosis type 2 (NF2) is a rare genetic disease that causes a wide range of disabilities leading to compromised quality of life (QOL). There is clear need for a validated disease-specific tool to assess quality of life among German-speaking patients with neurofibromatosis type 2 (NF2). The NFTI-QOL questionnaire has produced useful results in English-speaking cohorts.

Characterising methamphetamine use to inform health and social policies in Manitoba, Canada: a protocol for a retrospective cohort study using linked administrative data.

Introduction: Rising use of methamphetamine is causing significant public health concern in Canada. The biological and behavioural effects of methamphetamine range from wakefulness, vigour and euphoria to adverse physical health outcomes like myocardial infarction, haemorrhagic stroke, arrhythmia and seizure. It can also cause severe psychological complications such as psychosis.

Supplementary data for the mediation effect of personality functioning - Gender differences, separate analyses of depression and anxiety symptoms and inferential statistics of the relationship between personality functioning and different types of child maltreatment.

This article provides supplementary data for the original research article 'The Mediation Effect of Personality Functioning Between Different Types of Child Maltreatment and the Development of Depression/Anxiety Symptoms - a German Representative Study' [1]. The representative data were acquired as part of a broader survey on different aspects of mental health in the German population. This supplementary data article contains the statistical analyses of the relationship between the different subtypes of child maltreatment (CM) and impairments of personality functioning, which were only presented as a diagram in the original article.

The mediation effect of personality functioning between different types of child maltreatment and the development of depression/anxiety symptoms - A German representative study.

Background: Child maltreatment (CM) is associated with an increased risk to develop symptoms of depression/anxiety across an individual's lifespan. Recent studies indicated that impairments in personality functioning might mediate this association. The purpose of this study is to add evidence of this mediating effect by regarding different types of CM (emotional, physical and sexual abuse as well as emotional and physical neglect) in the general population.

Concentration-QT modelling of the novel DHFR inhibitor P218 in healthy male volunteers.

Aims: Given the increasing emergence of drug resistance in Plasmodium, new antimalarials are urgently required. P218 is an aminopyridine that inhibits dihydrofolate reductase being developed as a malaria chemoprotective drug. Assessing the effect of new compounds on cardiac intervals is key during early drug development to determine their cardiac safety.

Comparing the consistency of electrocardiogram interval measurements by resting ECG versus 12-lead Holter.

In clinical trials, traditionally only a limited number of 12-lead resting electrocardiograms (ECGs) can be recorded and, thus, long intervals may elapse between assessment timepoints and valuable information may be missed during times when patients' cardiac electrical activity is not being monitored. These limitations have led to the increasing use of Holter recorders which provide continuous data registrations while reducing the burden on patients and freeing up time for clinical trial staff to perform other tasks. However, there is a shortage of data comparing the two approaches.

A Phase 1 Study to Investigate the Effects of Cortexolone 17α-Propionate, Also Known as Clascoterone, on the QT Interval Using the Meal Effect to Demonstrate ECG Assay Sensitivity.

Cortexolone 17α-propionate, also known as clascoterone, is a potent androgen receptor inhibitor intended for the topical treatment of skin diseases associated with androgenic pathway alterations. In nonclinical studies, cortexolone 17α-propionate was found to have a weak inhibitory effect on human Ether-à-go-go-Related Gene (hERG) potassium channels, which are vital for normal electrical activity in the heart. When used in a cream formulation, little cortexolone 17α-propionate is absorbed.

Lipid profiling of mouse intestinal organoids for studying APC mutations.

Inactivating mutations including both germline and somatic mutations in the adenomatous polyposis coli (APC) gene drives most familial and sporadic colorectal cancers. Understanding the metabolic implications of this mutation will aid to establish its wider impact on cellular behaviour and potentially inform clinical decisions. However, to date, alterations in lipid metabolism induced by APC mutations remain unclear.

Safety, Tolerability, and Dose Proportionality of a Novel Transdermal Fentanyl Matrix Patch and Bioequivalence With a Matrix Fentanyl Patch: Two Phase 1 Single-Center Open-Label, Randomized Crossover Studies in Healthy Japanese Volunteers.

Two open-label, single-dose, randomized crossover studies were conducted in healthy Japanesemen to (1) assess dose proportionality of 5 doses (1.38, 2.75, 5.

Modular multiantigen T cell epitope-enriched DNA vaccine against human leishmaniasis.

The leishmaniases are protozoal diseases that severely affect large populations in tropical and subtropical regions. There are only limited treatment options and preventative measures. Vaccines will be important for prevention, control and elimination of leishmaniasis, and could reduce the transmission and burden of disease in endemic populations.

Therapeutic vaccination for cancer immunotherapy: antigen selection and clinical responses.

Background: Because of its high specificity and low toxicity therapeutic vaccination is considered a desirable treatment for cancer. So far, however, the results of cancer vaccination trials have been disappointing, which is often attributed to the problem identifying appropriate vaccine antigens. Tumorassociated antigens are mostly autoantigens and therefore expected to be subject to immunosuppressive mechanisms.

MHC I stabilizing potential of computer-designed octapeptides.

Experimental results are presented for 180 in silico designed octapeptide sequences and their stabilizing effects on the major histocompatibility class I molecule H-2K(b). Peptide sequence design was accomplished by a combination of an ant colony optimization algorithm with artificial neural network classifiers. Experimental tests yielded nine H-2K(b) stabilizing and 171 nonstabilizing peptides.

Attractors in Sequence Space: Agent-Based Exploration of MHC I Binding Peptides.

Ant Colony Optimization (ACO) is a meta-heuristic that utilizes a computational analogue of ant trail pheromones to solve combinatorial optimization problems. The size of the ant colony and the representation of the ants' pheromone trails is unique referring to the given optimization problem. In the present study, we employed ACO to generate novel peptides that stabilize MHC I protein on the plasma membrane of a murine lymphoma cell line.

Treatment with sibutramine prior to Roux-en-Y gastric bypass leads to an improvement of metabolic parameters and to a reduction of liver size and operative time.

Background: Previous studies have shown that a preoperative weight loss is associated with better long-term outcome, fewer complications, and less time in the operating room in bariatric patients. However, preoperative weight loss is hard to achieve in many patients.

Methods: We, therefore, conducted a study in which 20 bariatric patients received 15 mg of the weight loss medication sibutramine prior to laparoscopic Roux-en-Y gastric bypass (RYGBP) while patients in the control group did not.

iUDB: an object-oriented system for modelling, integration and analysis of gene controlled metabolic networks.

The rate constant of an enzyme-catalysed reaction is one of the major target properties to understand protein function. Atomic-detail computer simulations can in principle be used to estimate rate constants from the energy profile along the reaction coordinate. For such simulations, molecular mechanics is combined with a quantum description of the reaction process.

BioDataServer: a SQL-based service for the online integration of life science data.

Regarding molecular biology, we see an exponential growth of data and knowledge. Among others, this fact is reflected in more than 300 molecular databases which are readily available on the Internet. The usage of these data requires integration tools capable of complex information fusion processes.