Stereochemistry in the disorder-order continuum of protein interactions.

Intrinsically disordered proteins can bind via the formation of highly disordered protein complexes without the formation of three-dimensional structure. Most naturally occurring proteins are levorotatory (L)-that is, made up only of L-amino acids-imprinting molecular structure and communication with stereochemistry. By contrast, their mirror-image dextrorotatory (D)-amino acids are rare in nature.

Is There a "Best" Way for Patients to Participate in Pharmacovigilance?

The underreporting of suspected adverse drug reactions hinders pharmacovigilance. Solutions to underreporting are oftentimes directed at clinicians and healthcare professionals. However, given the recent rise of public inclusion in medical science, solutions may soon begin more actively involving patients.

Immersive virtual reality in the treatment of auditory hallucinations: A PRISMA scoping review.

Background: A large group of psychiatric patients suffer from auditory hallucinations (AH) despite relevant treatment regimens. In mental health populations, AH tend to be verbal (AVH) and the content critical or abusive. Trials employing immersive virtual reality (VR) to treat mental health disorders are emerging.

What are side effects?

Side effects are ubiquitous in medicine and they often play a role in treatment decisions for patients and clinicians alike. Philosophers and health researchers often use side effects to illustrate issues with contemporary medical research and practice. However, technical definitions of 'side effect' differ among health authorities.

A nationwide observational study in heavily pretreated metastatic HER2-positive breast cancer patients.

Background: Current guidelines in HER2-positive metastatic breast cancer (mBC) recommend the combination of trastuzumab and a chemotherapeutic agent for 3rd line or later treatments. This study aims to describe the treatment of HER2-positive mBC in 3rd line or later after previous treatment with T-DM1 for mBC in a real-world setting.

Material And Methods: This observational population-based study included all women diagnosed with HER2-positive mBC in Denmark, previously treated with T-DM1 in the metastatic setting.

Update to the study protocol Face Your Fears: Virtual reality-based cognitive behavioral therapy (VR-CBT) versus standard CBT for paranoid ideations in patients with schizophrenia spectrum disorders: a randomized clinical trial.

We unfortunately need to make an update to our published study protocol that describes a significant change in the design of the study. The Committee on Health Research Ethics of the Capital Region Denmark recently rejected the approval of changing the primary outcome in the trial, on the invariable grounds that the trial has already commenced. It is therefore necessary to retain the Green Paranoid Thought Scale (GPTS) part B, ideas of persecution, as our primary outcome, and GPTS part A, ideas of social reference, as a secondary outcome, which is described opposite in our published study protocol.

Evolutionary fine-tuning of residual helix structure in disordered proteins manifests in complex structure and lifetime.

Transcription depends on complex networks, where folded hub proteins interact with intrinsically disordered transcription factors undergoing coupled folding and binding. For this, local residual structure, a prototypical feature of intrinsic disorder, is key. Here, we dissect the unexplored functional potential of residual structure by comparing structure, kinetics, and thermodynamics within the model system constituted of the DREB2A transcription factor interacting with the αα-hub RCD1-RST.

Are 'phase IV' trials exploratory or confirmatory experiments?

Exploratory experiments are widely characterized as experiments that do not test hypotheses. Experiments that do test hypotheses are characterized as confirmatory experiments. Philosophers have pointed out that research programmes can be both confirmatory and exploratory.

Face Your Fears: Virtual reality-based cognitive behavioral therapy (VR-CBT) versus standard CBT for paranoid ideations in patients with schizophrenia spectrum disorders: a randomized clinical trial.

Background: Schizophrenia spectrum disorders cause suffering for patients, relatives, and the surrounding society. Paranoid ideations, encompassing ideas of social reference and manifest persecutory delusions, are among the most frequent symptoms in this population and a cause of significant distress. Recent meta-analyses of cognitive behavioral therapy (CBT) for psychosis show small to moderate effect sizes in reducing paranoid ideations.

Innovative rehabilitating meal service programs for old people living at home: A randomized controlled pilot study.

Objective: To test the feasibility of a pilot study for a future definitive trial investigating the effect of different meal service programs for old people living at home.

Design: An 8-week randomized controlled trial was performed.

Setting: Three municipalities in the Nordic country, Denmark.

Flanking Disorder of the Folded αα-Hub Domain from Radical Induced Cell Death1 Affects Transcription Factor Binding by Ensemble Redistribution.

Protein intrinsic disorder is essential for organization of transcription regulatory interactomes. In these interactomes, the majority of transcription factors as well as their interaction partners have co-existing order and disorder. Yet, little attention has been paid to their interplay.

Excessive Weight Gain Followed by Catch-Down in Exclusively Breastfed Infants: An Exploratory Study.

Some infants experience excessive weight gain (EWG) during exclusive breastfeeding, but causes and consequences are unknown. The objective was to identify factors associated with early EWG. Infants with EWG (HW-group) were examined at 5, 9 and 18 mo and compared to a breastfed group with normal weight gain (NW-group).

Pretreatment Fasting Plasma Glucose Modifies Dietary Weight Loss Maintenance Success: Results from a Stratified RCT.

Objective: Levels of fasting plasma glucose (FPG) and fasting insulin (FI) were studied as diet-specific prognostic markers for successful weight loss maintenance in participants with overweight.

Methods: After losing ≥ 8% of body weight, participants received one of three ad libitum diets for 6 months: (1) a moderate-fat diet high in monounsaturated fatty acids (MUFA); a low-fat, high-fiber diet (Nordic Nutrition Recommendations [NNR]); and the Average Danish Diet (ADD). Participants were categorized as having low (< 90 mg/dL) or high (90-105 mg/dL) FPG based on preintervention values.

Isolation and chemoenzymatic treatment of glycoalkaloids from green, sprouting and rotting Solanum tuberosum potatoes for solanidine recovery.

The estimation of glycoalkaloids in the flesh of different types of decayed potatoes was evaluated. The results showed that turned green and also sprouting or rotting potato flesh contain high amounts of toxic solanine and chaconine, exceeding by 2-5-fold the recommended limit, and ranging from 2578±86mg/kg to 5063±230mg/kg of dry weight potato flesh. For safety consideration, these decayed potatoes should be systematically set aside.

The effect of three different ad libitum diets for weight loss maintenance: a randomized 18-month trial.

Purpose: To test the effect of three diets in their ability to sustain weight loss and improve type 2 diabetes (T2D) and cardiovascular disease (CVD) risk markers after 18-month intervention.

Methods: Following a ≥8 % weight loss, 131 healthy, overweight/obese (BMI ± SD 31.5 ± 2.

Recurrences after intensity modulated radiotherapy for head and neck squamous cell carcinoma more likely to originate from regions with high baseline [18F]-FDG uptake.

Background And Purpose: To analyze the recurrence pattern in relation to target volumes and (18)F-fluorodeoxyglucose (FDG) uptake on positron emission tomography in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive chemoradiation.

Material And Methods: 520 patients received radiotherapy for HNSCC from 2005 to 2009. Among 100 patients achieving complete clinical response and a later recurrence, 39 patients with 48 loco-regional failures had a recurrence CT scan before any salvage therapy.

Postprandial coagulation activation in overweight individuals after weight loss: acute and long-term effects of a high-monounsaturated fat diet and a low-fat diet.

Diet is important in the prevention of cardiovascular disease, and it has been suggested that a high-MUFA diet is more cardioprotective than a low-fat diet. We hypothesised that the postprandial thrombotic risk profile is improved most favourably by a high-MUFA diet compared with a low-fat diet. This was tested in a parallel intervention trial on overweight individuals (aged 28.

Health effect of the New Nordic Diet in adults with increased waist circumference: a 6-mo randomized controlled trial.

Background: The regional Mediterranean Diet has been associated with lower risk of disease.

Objective: We tested the health effects of the New Nordic Diet (NND), which is a gastronomically driven regional, organic, and environmentally friendly diet, in a carefully controlled but free-living setting.

Design: A total of 181 centrally obese men and women, with a mean (range) age of 42 y (20-66 y), body mass index (in kg/m(2)) of 30.

Failure-probability driven dose painting.

Purpose: To demonstrate a data-driven dose-painting strategy based on the spatial distribution of recurrences in previously treated patients. The result is a quantitative way to define a dose prescription function, optimizing the predicted local control at constant treatment intensity. A dose planning study using the optimized dose prescription in 20 patients is performed.

Interobserver delineation variation in lung tumour stereotactic body radiotherapy.

Objectives: In radiotherapy, delineation uncertainties are important as they contribute to systematic errors and can lead to geographical miss of the target. For margin computation, standard deviations (SDs) of all uncertainties must be included as SDs. The aim of this study was to quantify the interobserver delineation variation for stereotactic body radiotherapy (SBRT) of peripheral lung tumours using a cross-sectional study design.

Methods for estimating the site of origin of locoregional recurrence in head and neck squamous cell carcinoma.

Purpose: Methods to estimate the likely origin of recurrences after radiation therapy for head and neck squamous cell carcinoma are compared.

Methods And Materials: A total of 25 patients meeting the following inclusion criteria were randomly selected: curatively intended intensity-modulated radiotherapy planned on a positron emission tomography-computed tomography (PET/CT) scan during the period 2005-2009; squamous cell carcinoma in the oral cavity, pharynx or larynx; complete clinical response followed by locoregional recurrence; and a CT scan at recurrence before any salvage therapy. Exclusion criteria were previous cancer in the area, surgery prior to radiotherapy, or a synchronous cancer.

Bisubstrate specificity in histidine/tryptophan biosynthesis isomerase from Mycobacterium tuberculosis by active site metamorphosis.

In histidine and tryptophan biosynthesis, two related isomerization reactions are generally catalyzed by two specific single-substrate enzymes (HisA and TrpF), sharing a similar (β/α)(8)-barrel scaffold. However, in some actinobacteria, one of the two encoding genes (trpF) is missing and the two reactions are instead catalyzed by one bisubstrate enzyme (PriA). To unravel the unknown mechanism of bisubstrate specificity, we used the Mycobacterium tuberculosis PriA enzyme as a model.

Effects on markers of inflammation and endothelial cell function of three ad libitum diets differing in type and amount of fat and carbohydrate: a 6-month randomised study in obese individuals.

Diet is important for the prevention of CVD, and diets high in MUFA might be more cardioprotective than low-fat diets. We hypothesise that inflammation and endothelial cell function will be improved most favourably by a high-MUFA diet compared with a low-fat diet. This was tested in a parallel randomised intervention trial on overweight individuals (aged 28·2 (SD 4·6) years) assigned to a diet moderate in the amount of fat (35-45% of energy; >20% of fat as MUFA; MUFA diet, n 39), a low-fat (20-30% of energy) diet (LF diet, n 43) or a control diet (35 % of energy as fat, n 24) for 6 months after weight loss.