Tunable CD44-specific cellular retargeting with hyaluronic acid nanoshells.

Purpose: In this work we specifically investigate the molecular weight (Mw) dependent combinatorial properties of hyaluronic acid (HA) for exhibiting stealth and targeting properties using different Mw HA nanoshells to tune nanoparticle retargeting to CD44-expressing cancer cells.

Methods: HA of different Mw was covalently grafted onto model polystyrene nanoparticles and advanced surface analysis by X-ray photoelectron spectroscopy performed to quantify and evaluate the effect of the coating procedure. Specific CD44-mediated retargeting was investigated by flow cytometry and confocal microscopy using isogenic D44-deficient and CD44-expressing MCF-7 breast adenocarcinoma cells.

Anxiolytic-like effects after vector-mediated overexpression of neuropeptide Y in the amygdala and hippocampus of mice.

Neuropeptide Y (NPY) causes anxiolytic- and antidepressant-like effects after central administration in rodents. These effects could theoretically be utilized in future gene therapy for anxiety and depression using viral vectors for induction of overexpression of NPY in specific brain regions. Using a recombinant adeno-associated viral (rAAV) vector, we addressed this idea by testing effects on anxiolytic- and depression-like behaviours in adult mice after overexpression of NPY transgene in the amygdala and/or hippocampus, two brain regions implicated in emotional behaviours.

Deciding treatment for miscarriage--experiences of women and healthcare professionals.

Introduction: Women experiencing miscarriage are offered a choice of different treatments to terminate their wanted pregnancy at a time when they are often shocked and distressed. Women's and healthcare professionals' experiences of the decision-making process are not well described. We aimed to gain insight into this process and the circumstances that may affect it.

Genetic aspects of lone atrial fibrillation: what do we know?

Atrial fibrillation (AF) is the most common cardiac arrhythmia. A subgroup of patients presents with AF without traditional risk factors and is diagnosed before the age of 60 years. Such patients are commonly referred as having "lone AF" and comprise 10-20% of all cases.

Electroconvulsive stimulation, but not chronic restraint stress, causes structural alterations in adult rat hippocampus--a stereological study.

The neurobiological mechanisms underlying depression are not fully understood. Only a few previous studies have used validated stereological methods to test how stress and animal paradigms of depression affect adult hippocampal neurogenesis and whether antidepressant therapy can counteract possible changes in an animal model. Thus, in this study we applied methods that are state of the art in regard to stereological cell counting methods.

Integrating genetic, transcriptional, and functional analyses to identify 5 novel genes for atrial fibrillation.

Background: Atrial fibrillation (AF) affects >30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood.

Methods And Results: To identify new AF-related genes, we used a multifaceted approach, combining large-scale genotyping in 2 ethnically distinct populations, cis-eQTL (expression quantitative trait loci) mapping, and functional validation.

SCN10A/Nav1.8 modulation of peak and late sodium currents in patients with early onset atrial fibrillation.

Aims: To test the hypothesis that vulnerability to atrial fibrillation (AF) is associated with rare coding sequence variation in the SCN10A gene, which encodes the voltage-gated sodium channel isoform NaV1.8 found primarily in peripheral nerves and to identify potentially disease-related mechanisms in high-priority rare variants using in-vitro electrophysiology.

Methods And Results: We re-sequenced SCN10A in 274 patients with early onset AF from the Vanderbilt AF Registry to identify rare coding variants.

The microbial detection array for detection of emerging viruses in clinical samples--a useful panmicrobial diagnostic tool.

Emerging viruses are usually endemic to tropical and sub-tropical regions of the world, but increased global travel, climate change and changes in lifestyle are believed to contribute to the spread of these viruses into new regions. Many of these viruses cause similar disease symptoms as other emerging viruses or common infections, making these unexpected pathogens difficult to diagnose. Broad-spectrum pathogen detection microarrays containing probes for all sequenced viruses and bacteria can provide rapid identification of viruses, guiding decisions about treatment and appropriate case management.

New population-based exome data question the pathogenicity of some genetic variants previously associated with Marfan syndrome.

Background: Marfan syndrome (MFS) is a rare autosomal dominantly inherited connective tissue disorder with an estimated prevalence of 1:5,000. More than 1000 variants have been previously reported to be associated with MFS. However, the disease-causing effect of these variants may be questionable as many of the original studies used low number of controls.

Electrocardiographic precordial ST-segment deviations and the risk of cardiovascular death: results from the Copenhagen ECG Study.

Background: We sought to perform a study assessing the association between electrocardiographic ST-segment deviations and cardiovascular death (CVD), in relation to sex and age (≥ and <65 years), in a large primary care population without overt ischemic heart disease.

Methods And Results: Using computerized analysis of ECGs from 285 194 persons, we evaluated the association between precordial ST-segment deviations and the risk of CVD. All data on medication, comorbidity, and outcomes were retrieved from Danish registries.

Gain-of-function mutations in potassium channel subunit KCNE2 associated with early-onset lone atrial fibrillation.

Aims: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Disturbances in cardiac potassium conductance are considered as one of the disease mechanisms in AF. We aimed to investigate if mutations in potassium-channel β-subunits KCNE2 and KCNE3 are associated with early-onset lone AF.

Chronic non-bloody diarrhoea: a prospective study in Malmö, Sweden, with focus on microscopic colitis.

Background: Chronic non-bloody diarrhoea affects up to 5% of the population. Microscopic colitis is one of the most common causes, encompassing the subtypes collagenous colitis and lymphocytic colitis. The diagnosis of microscopic colitis is made by histological examination of colonic mucosal biopsy specimens.

Brugada syndrome risk loci seem protective against atrial fibrillation.

Several studies have shown an overlap between genes involved in the pathophysiological mechanisms of atrial fibrillation (AF) and Brugada Syndrome (BrS). We investigated whether three single-nucleotide polymorphisms (SNPs) (rs11708996; G>C located intronic to SCN5A, rs10428132; T>G located in SCN10A, and rs9388451; T>C located downstream to HEY2) at loci associated with BrS in a recent genome-wide association study (GWAS) also were associated with AF. A total of 657 patients diagnosed with AF and a control group comprising 741 individuals free of AF were included.

Risk prediction of cardiovascular death based on the QTc interval: evaluating age and gender differences in a large primary care population.

Aims: Using a large, contemporary primary care population we aimed to provide absolute long-term risks of cardiovascular death (CVD) based on the QTc interval and to test whether the QTc interval is of value in risk prediction of CVD on an individual level.

Methods And Results: Digital electrocardiograms from 173 529 primary care patients aged 50-90 years were collected during 2001-11. The Framingham formula was used for heart rate-correction of the QT interval.

Investigations of the Navβ1b sodium channel subunit in human ventricle; functional characterization of the H162P Brugada syndrome mutant.

Brugada syndrome (BrS) is a rare inherited disease that can give rise to ventricular arrhythmia and ultimately sudden cardiac death. Numerous loss-of-function mutations in the cardiac sodium channel Nav1.5 have been associated with BrS.

Nationwide (Denmark) study of symptoms preceding sudden death due to arrhythmogenic right ventricular cardiomyopathy.

In this study, we investigated medical history and symptoms before death in all subjects aged 1 to 35 years who died a sudden cardiac death (SCD) from arrhythmogenic right ventricular cardiomyopathy (ARVC) in Denmark in the years 2000 to 2006. All deaths (n=6,629) in subjects aged 1 to 35 years in Denmark in the period 2000 to 2006 were included. A total of 16 cases of SCD due to ARVC were identified based on histopathologic examination.

Genetic variation in the two-pore domain potassium channel, TASK-1, may contribute to an atrial substrate for arrhythmogenesis.

The two-pore domain potassium channel, K2P3.1 (TASK-1) modulates background conductance in isolated human atrial cardiomyocytes and has been proposed as a potential drug target for atrial fibrillation (AF). TASK-1 knockout mice have a predominantly ventricular phenotype however, and effects of TASK-1 inactivation on atrial structure and function have yet to be demonstrated in vivo.

Very early-onset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Currently, 14 genes important for ion channel function, intercellular signaling, and homeostatic control have been associated with AF.

Objective: We hypothesized that rare genetic variants in genes previously associated with AF had a higher prevalence in early-onset lone AF patients than in the background population.

Genetic modifier of the QTc interval associated with early-onset atrial fibrillation.

Background: Both shortening and prolongation of the QTc interval have been associated with atrial fibrillation (AF). We investigated whether 8 single nucleotide polymorphisms (SNPs) at loci previously shown to affect QTc interval duration were associated with lone AF.

Methods: We included 358 patients diagnosed with lone AF (defined as onset of AF at < 50 years of age in the absence of traditional cardiovascular risk factors) and a control group consisting of 751 individuals free of AF.

New exome data question the pathogenicity of genetic variants previously associated with catecholaminergic polymorphic ventricular tachycardia.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal, rare hereditary disease with an estimated prevalence of 1:10 000. The genetic variants that cause CPVT are usually highly penetrant. To date, about 189 variants in 5 genes (RYR2, CASQ2, CALM1, TRND, and KCNJ2) have been associated with CPVT pathogenesis.

Effect of calcipotriene plus betamethasone dipropionate topical suspension on the hypothalamic-pituitary-adrenal axis and calcium homeostasis in subjects with extensive psoriasis vulgaris: an open, non-controlled, 8-week trial.

Background: The two-compound topical suspension/gel containing calcipotriene plus betamethasone dipropionate is effective and safe in the treatment of psoriasis on the body and scalp within the general psoriasis patient population.

Objective: To evaluate the systemic effects of once-daily use of two-compound topical suspension/gel on the hypothalamic-pituitary-adrenal (HPA) axis and calcium homeostasis in subjects with extensive psoriasis vulgaris.

Methods: An open-label, single-group, 8-week trial in 43 subjects with extensive psoriasis covering 15-30% of the body surface area.

The emotional content of life stories: positivity bias and relation to personality.

We examined whether past and future negative life story events, compared to past and future positive events, were less likely to be related to life story chapters and situated at a greater temporal distance from the present. We also examined relations between life stories and personality traits. Three hundred ten students and 160 middle-aged adults completed a measure of personality traits and identified chapters as well as past and future events in their life story.

The genetic component of Brugada syndrome.

Brugada syndrome (BrS) is a clinical entity first described in 1992. BrS is characterized by ST-segment elevations in the right precordial leads and susceptibility to ventricular arrhythmias and sudden cardiac death. It affects young subjects, predominantly males, with structurally normal hearts.