Sulindac prevents increased mitochondrial VDAC1 expression and cell surface mistargeting induced by pathological conditions in retinal cells.

Diabetic retinopathy (DR) continues to be the primary cause of vision loss in poorly controlled diabetic subjects. The molecular mechanisms underlying retinal pigment epithelium (RPE) cell dysfunction in DR still remain elusive. We investigated the role of mitochondrial volt-age-dependent anion channel 1 (VDAC1) in RPE dysfunction under glucotoxic and inflammatory conditions.

An experimental study on lung deposition of inhaled 2 μm particles in relation to lung characteristics and deposition models.

Background: The understanding of inhaled particle respiratory tract deposition is a key link to understand the health effects of particles or the efficiency for medical drug delivery via the lung. However, there are few experimental data on particle respiratory tract deposition, and the existing data deviates considerably when comparing results for particles > 1 μm.

Methods: We designed an experimental set-up to measure deposition in the respiratory tract for particles > 1 μm, more specifically 2.

Cognitive performance in hospitalized patients with severe or extreme anorexia nervosa.

Purpose: Severe malnourishment may reduce cognitive performance in anorexia nervosa (AN). We studied cognitive functioning during intensive nutritional and medical stabilization in patients with severe or extreme AN and investigated associations between weight gain and cognitive improvement.

Methods: A few days after admission to a specialized hospital unit, 33 patients with severe or extreme AN, aged 16-42 years, completed assessments of memory, cognitive flexibility, processing speed, and attention.

Altered Adipocyte Cell Size Distribution Prior to Weight Loss in the R6/2 Model of Huntington's Disease.

Background: Metabolic alterations contribute to disease onset and prognosis of Huntington's disease (HD). Weight loss in the R6/2 mouse model of HD is a consistent feature, with onset in mid-to-late stage of disease.

Objective: In the present study, we aimed to investigate molecular and functional changes in white adipose tissue (WAT) that occur at weight loss in R6/2 mice.

Cognitive Flexibility in Hospitalized Patients with Severe or Extreme Anorexia Nervosa: A Case-Control Study.

Objective: To investigate whether cognitive inflexibility could be identified using the Wisconsin Card Sorting Test (WCST) in patients with severe and extreme anorexia nervosa (AN) compared to healthy control participants (HCs).

Method: We used the WCST to assess 34 patients with AN (mean age: 25.9 years, mean body mass index (BMI): 13.

Trauma Experiences Are Common in Anorexia Nervosa and Related to Eating Disorder Pathology but Do Not Influence Weight-Gain during the Start of Treatment.

Objective: The main characteristics of Anorexia Nervosa (AN) in adults are restriction of energy intake relative to requirements leading to significant weight loss, disturbed body image, and intense fear of becoming fat. Traumatic experiences (TE) have been reported as common, although less is known about the relationship with other symptoms in severe AN. We investigated the presence of TE, PTSD, and the relation between TE, eating disorder (ED) symptoms, and other symptoms in moderate to severe AN ( = 97) at admission to inpatient weight-restoration treatment.

Intraputamenal Cerebral Dopamine Neurotrophic Factor in Parkinson's Disease: A Randomized, Double-Blind, Multicenter Phase 1 Trial.

Background: Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that protects dopamine neurons and improves motor function in animal models of Parkinson's disease (PD).

Objective: The primary objectives of this study were to assess the safety and tolerability of both CDNF and the drug delivery system (DDS) in patients with PD of moderate severity.

Methods: We assessed the safety and tolerability of monthly intraputamenal CDNF infusions in patients with PD using an investigational DDS, a bone-anchored transcutaneous port connected to four catheters.

Anorexia Nervosa With Comorbid Severe Depression: A Systematic Scoping Review of Brain Stimulation Treatments.

Major depressive disorder (MDD) is highly prevalent in individuals with anorexia nervosa (AN) and is a predictor of greater clinical severity. However, there is a limited amount of evidence supporting the use of psychotropic medications for its management. A systematic scoping review was conducted to assess the current literature on brain stimulation treatments for AN with comorbid MDD, with a specific focus on MDD treatment response and weight restoration.

Ablation of GPR56 Causes β-Cell Dysfunction by ATP Loss through Mistargeting of Mitochondrial VDAC1 to the Plasma Membrane.

The activation of G Protein-Coupled Receptor 56 (GPR56), also referred to as Adhesion G-Protein-Coupled Ceceptor G1 (ADGRG1), by Collagen Type III (Coll III) prompts cell growth, proliferation, and survival, among other attributes. We investigated the signaling cascades mediating this functional effect in relation to the mitochondrial outer membrane voltage-dependent anion Channel-1 (VDAC1) expression in pancreatic β-cells. GPR56KD attenuated the Coll III-induced suppression of P70S6K, JNK, AKT, NFκB, STAT3, and STAT5 phosphorylation/activity in INS-1 cells cultured at 20 mM glucose (glucotoxicity) for 72 h.

Mapping length of inpatient treatment duration and year-wise relapse rates in eating disordered populations in a well-defined Western-European healthcare region across 1998-2020.

Objectives: Updated international guideline recommendations for AN inpatient care rely on expert opinions/observational evidence and promote extended inpatient stays, warranting investigation using higher-level ecological evidence.

Methods: The study was conducted according to Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Data encompassing 13,885 ED inpatients (5336 adolescents and 8549 adults) was retrieved from Swedish public health registries.

Anorexia Nervosa: Reduction in Depression during Inpatient Treatment Is Closely Related to Reduction in Eating Disorder Psychopathology.

Objective: Anorexia nervosa (AN) is a severe mental disorder frequently associated with high scores of depressiveness. We examined the short-term effects of inpatient treatment on depressiveness and eating disorder (ED) psychopathology using the self-rating Major Depression Inventory (MDI) and Eating Disorder Examination questionnaire (EDEq) for patients with AN. Material: Forty-nine patients with AN, all part of the PROspective Longitudinal all-comer inclusion study on EDs (PROLED), were observed over eight weeks with baseline psychometric measures, EDE-q at baseline and endpoint, and weekly MDI self-scoring.

Estimating the Effect of Motivational Interventions in Patients with Eating Disorders: A Systematic Review and Meta-Analysis.

Motivation to change behavior is seen as an important factor in achieving a better treatment effect in patients with eating disorders (ED). The aim of this systematic review was to assess whether motivational interviewing (MI) and motivational enhancement therapy (MET) might (1) increase motivation to change behavior and (2) improve eating disorder psychopathology (EDP) and body mass index (BMI) in patients with ED. To investigate this, a literature search was conducted on 9 March 2021 on four scientific databases: Cochrane, Embase (Ovid), MEDLINE (PubMed), and PsycInfo (EBSCO).

Why Do Women with Eating Disorders Decline Treatment? A Qualitative Study of Barriers to Specialized Eating Disorder Treatment.

Despite the fact that eating disorders (EDs) are conditions that are potentially life-threatening, many people decline treatment. The aim of this study was to investigate why women decline specialized ED treatment, including their viewpoints on treatment services. Eighteen semi-structured qualitative interviews were conducted with women who had declined inpatient or outpatient specialized ED treatment.

Inpatient Weight Restoration Treatment Is Associated with Decrease in Post-Meal Anxiety.

Objective: Anorexia nervosa (AN) is characterized by weight loss, distorted body image with fear of becoming fat and associated with anxiety, especially in relation to food intake. Anxiety in relation to meals and weight restoration remains a major challenge in the treatment of AN. We examined the effects of inpatient weight restoration treatment on levels of post-meal anxiety using visual analogue scale (VAS) ratings in patients with AN.

Genetically Targeted Clinical Trials in Parkinson's Disease: Learning from the Successes Made in Oncology.

Clinical trials in neurodegenerative disorders have been associated with high rate of failures, while in oncology, the implementation of precision medicine and focus on genetically defined subtypes of disease and targets for drug development have seen an unprecedented success. With more than 20 genes associated with Parkinson's disease (PD), most of which are highly penetrant and often cause early onset or atypical signs and symptoms, and an increasing understanding of the associated pathophysiology culminating in dopaminergic neurodegeneration, applying the technologies and designs into the field of neurodegeneration seems a logical step. This review describes some of the methods used in oncology clinical trials and some attempts in Parkinson's disease and the potential of further implementing genetics, biomarkers and smart clinical trial designs in this disease area.

The human melanoma proteome atlas-Defining the molecular pathology.

The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in-depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma.

The Human Melanoma Proteome Atlas-Complementing the melanoma transcriptome.

The MM500 meta-study aims to establish a knowledge basis of the tumor proteome to serve as a complement to genome and transcriptome studies. Somatic mutations and their effect on the transcriptome have been extensively characterized in melanoma. However, the effects of these genetic changes on the proteomic landscape and the impact on cellular processes in melanoma remain poorly understood.

Cognitive Function in Adults with Enduring Anorexia Nervosa.

Anorexia Nervosa (AN) is a severe and often enduring disorder characterized by restriction of food intake, low body weight, fear of weight gain, and distorted body image. Investigations on cognition performance in AN patients have yielded conflicting results. Using an established and sensitive computerized cognitive test battery, we aimed to assess core aspects of cognitive function, including attention span, information processing, reasoning, working and episodic memory, in AN patients and controls.

Weight Gain in Adults with Avoidant/Restrictive Food Intake Disorder Compared to Restrictive Anorexia Nervosa-Pilot Findings from a Longitudinal Study.

Background: Avoidant/Restrictive Food Intake Disorder (ARFID) is characterized by persistent failure to meet nutritional needs, absence of body image distortion and often low body weight. Weight restorative treatment in ARFID-adults is provided for as in Anorexia Nervosa (AN), while the effect is unknown. The aim was to compare weight gain between ARFID and restrictive subtype of AN (AN-R), including exploring impact of medical factors and psychopathology.

Clinical Evaluation of the Polygenetic Background of Blood Pressure in the Population-Based Setting.

The clinical value of the polygenetic component of blood pressure (BP) is commonly questioned. We evaluated a genetic risk score for BP (BP-GRS), based on the most recently published genome-wide association studies variants that were significantly associated with either systolic BP or diastolic BP, for prediction of hypertension and cardiovascular end points. The genotyping was performed in 2 urban-based prospective cohorts: the Malmö Diet and Cancer (n=29 295) and the Malmö Preventive Project (n=9367) and a weighted BP-GRS based on 858 SNPs was calculated.

Increased intestinal permeability and gut dysbiosis in the R6/2 mouse model of Huntington's disease.

Huntington's disease (HD) is a progressive, multifaceted neurodegenerative disease associated with weight loss and gut problems. Under healthy conditions, tight junction (TJ) proteins maintain the intestinal barrier integrity preventing bacterial translocation from the intestinal lumen to the systemic circulation. Reduction of TJs expression in Parkinson's disease patients has been linked with increased intestinal permeability-leaky gut syndrome.

Study protocol of comprehensive risk evaluation for anorexia nervosa in twins (CREAT): a study of discordant monozygotic twins with anorexia nervosa.

Background: Anorexia nervosa (AN) is a severe disorder, for which genetic evidence suggests psychiatric as well as metabolic origins. AN has high somatic and psychiatric comorbidities, broad impact on quality of life, and elevated mortality. Risk factor studies of AN have focused on differences between acutely ill and recovered individuals.

Comorbid depression as a negative predictor of weight gain during treatment of anorexia nervosa: A systematic scoping review.

Background: Anorexia nervosa (AN) is a serious mental illness with high rates of relapse and mortality. Psychiatric comorbidities are common but their impact on the prognosis is largely unknown.

Objective: The aim was to investigate the influence of psychiatric comorbidity on weight gain during treatment of AN.