Use of 2,6-diaminopurine as a potent suppressor of UGA premature stop codons in cystic fibrosis.

Nonsense mutations are responsible for around 10% of cases of genetic diseases, including cystic fibrosis. 2,6-diaminopurine (DAP) has recently been shown to promote efficient readthrough of UGA premature stop codons. In this study, we show that DAP can correct a nonsense mutation in the Cftr gene in vivo in a new CF mouse model, in utero, and through breastfeeding, thanks, notably, to adequate pharmacokinetic properties.

Macrophage-Colony-Stimulating Factor Receptor Enhances Prostate Cancer Cell Growth and Aggressiveness In Vitro and In Vivo and Increases Osteopontin Expression.

Prostate cancer is a major public health concern and one of the most prevalent forms of cancer worldwide. The definition of altered signaling pathways implicated in this complex disease is thus essential. In this context, abnormal expression of the receptor of Macrophage Colony-Stimulating Factor-1 (M-CSF or CSF-1) has been described in prostate cancer cells.

The Accuracy of the Patient Health Questionnaire-9 Algorithm for Screening to Detect Major Depression: An Individual Participant Data Meta-Analysis.

Background: Screening for major depression with the Patient Health Questionnaire-9 (PHQ-9) can be done using a cutoff or the PHQ-9 diagnostic algorithm. Many primary studies publish results for only one approach, and previous meta-analyses of the algorithm approach included only a subset of primary studies that collected data and could have published results.

Objective: To use an individual participant data meta-analysis to evaluate the accuracy of two PHQ-9 diagnostic algorithms for detecting major depression and compare accuracy between the algorithms and the standard PHQ-9 cutoff score of ≥10.

Relationship Between Different Experimental Measures of Distorted Symptom Perception in Functional Syndrome Patients.

Objective: Patients with functional somatic syndromes show reduced correspondence between induced physiological changes and self-reported symptoms in a rebreathing paradigm, as well as elevated symptoms unrelated to physiological changes after induction of negative affective states in an affective picture-viewing paradigm. Detailed results of both paradigms separately were published elsewhere. The main goal of the current report is to describe the relationship between the responses to these two paradigms measuring distortions in symptom perception in a well-described sample of patients with fibromyalgia and/or chronic fatigue syndrome.

Probability of major depression diagnostic classification using semi-structured versus fully structured diagnostic interviews.

Background: Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used.

Negative Affectivity, Depression, and Resting Heart Rate Variability (HRV) as Possible Moderators of Endogenous Pain Modulation in Functional Somatic Syndromes.

Several studies have shown that patients with functional somatic syndromes (FSS) have, on average, deficient endogenous pain modulation (EPM), as well as elevated levels of negative affectivity (NA) and high comorbidity with depression and reduced resting heart rate variability (HRV) compared to healthy controls (HC). The goals of this study were (1) to replicate these findings and (2) to investigate the moderating role of NA, depression, and resting HRV in EPM efficiency within a patient group with fibromyalgia and/or chronic fatigue syndrome (CFS). Resting HRV was quantified as the root mean square of successive differences between inter-beat intervals (RMSSD) in rest, a vagally mediated time domain measure of HRV.

Perception of induced dyspnea in fibromyalgia and chronic fatigue syndrome.

Objective: Dyspnea perception is distorted in patients with medically unexplained dyspnea. The goals of this study were 1) to replicate these results in patients with fibromyalgia and/or chronic fatigue syndrome (CFS), and 2) to investigate predictors of distorted symptom perception within the patient group, with a focus on negative affectivity (NA), psychiatric comorbidity and somatic symptom severity.

Methods: Seventy-three patients diagnosed with fibromyalgia and/or CFS and 38 healthy controls (HC) completed a rebreathing paradigm, consisting of a baseline (60s of room air), a rebreathing phase (150s, gradually increasing ventilation, partial pressure of CO in the blood, and self-reported dyspnea), and a recovery phase (150s of room air).

Glucocorticoid receptor DNA methylation and childhood trauma in chronic fatigue syndrome patients.

Objective: Although the precise mechanisms are not yet understood, previous studies have suggested that chronic fatigue syndrome (CFS) is associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation and trauma in early childhood. Consistent with findings suggesting that early life stress-induced DNA methylation changes may underlie dysregulation of the HPA axis, we previously found evidence for the involvement of glucocorticoid receptor (GR) gene (NR3C1) methylation in whole blood of CFS patients.

Methods: In the current study, we assessed NR3C1-1F region DNA methylation status in peripheral blood from a new and independent sample of 80 female CFS patients and 91 female controls.

Inducing Somatic Symptoms in Functional Syndrome Patients: Effects of Manipulating State Negative Affect.

Objective: Induction of negative affective states can enhance bodily symptoms in high habitual symptom reporters among healthy persons and in patients with irritable bowel syndrome. The aims of this study were to replicate this effect in patients with fibromyalgia and chronic fatigue syndrome and to investigate the role of moderators, focusing on alexithymia, negative affectivity, and absorption.

Methods: Patients with fibromyalgia and/or chronic fatigue syndrome (n = 81) and HCs (n = 41) viewed series of neutral, positive, and negative affective pictures.

Long-term methylphenidate intake in chronic fatigue syndrome.

Objective: Concentration disturbances are frequent in chronic fatigue syndrome (CFS). In a placebo-controlled double-blind crossover study, methylphenidate over 4 weeks was superior to placebo in the relief of fatigue and concentration disturbance. This observational study describes the effect of long-term methylphenidate intake on fatigue, concentration, and daily life activities, as reported by the patients themselves.

Associative stigma in family members of psychotic patients in Flanders: An exploratory study.

Aim: To assess presence and severity of associative stigma in family members of psychotic patients and factors for higher associative stigma.

Methods: Standardized semi-structured interview of 150 family members of psychotic patients receiving full time treatment. This study on associative stigma in family members of psychotic patients was part of a larger research program on the burden of the family, using "Interview for the Burden of the Family" and the chapters stigma, treatment and attribution from the "Family interview Schedule".

In vivo type 1 cannabinoid receptor availability in Alzheimer's disease.

The endocannabinoid system (ECS) is an important modulatory and potentially neuroprotective homeostatic system in the brain. In Alzheimer's disease (AD), the role of type 1 cannabinoid receptor (CB₁R) is unclear, with contradictory findings in post-mortem studies showing upregulation, downregulation or unchanged CB₁R status. We have investigated CB₁R availability in vivo in patients with AD, in relation to amyloid deposition, cognitive functioning and apolipoprotein E (ApoE) genotype.

Attachment in old age: theoretical assumptions, empirical findings and implications for clinical practice.

Contemporary theoretical models that conceptualize attachment as a biologically-based behavioral system that is activated under threat offer a heuristic theoretical framework to understand processes involved in aging and particularly individual differences in coping with the inevitable losses associated with aging and age-related disease, including dementia. This paper provides a systematic qualitative review of research concerning attachment in old age published between 1983 and June 2012. Four major findings emerged.

Relationship between anxiety and gastric sensorimotor function in functional dyspepsia.

Objective: To investigate the relationship between anxiety and gastric sensorimotor function in patients with (hypersensitive) functional dyspepsia (FD). Comorbidity between FD and anxiety disorders is high. In FD, epigastric pain is associated with gastric hypersensitivity and neuroticism, a personality trait related to anxiety.

Evaluation of short-term responsiveness and cutoff values of inflammatory bowel disease questionnaire in Crohn's disease.

Background: The inflammatory bowel disease questionnaire (IBDQ) is a frequently used outcome parameter in clinical trials. Whereas the validity and reproducibility of the IBDQ have been extensively studied, there are limited data on its short-term responsiveness and cutoff values for remission and partial clinical response.

Methods: The IBDQ score and its bowel (BD), systemic (SysD), emotional (ED), and social (SocD) dimensions were tested for responsiveness in a cohort of 224 patients with Crohn's disease (CD) treated with infliximab for refractory luminal disease.

Does methylphenidate reduce the symptoms of chronic fatigue syndrome?

Purpose: Chronic fatigue syndrome is a clinical entity consisting of prolonged and debilitating fatigue in which concentration disturbances are very frequent. Until now, no medical treatment has shown any efficacy. The objectives of this study were to investigate the short-term effects of methylphenidate, an amphetamine derivative, on fatigue, concentration disturbances, and quality of life.

Regional brain activation during proximal stomach distention in humans: A positron emission tomography study.

Background & Aims: Hypersensitivity to proximal gastric distention due to abnormal central nervous system processing of visceral stimuli has been suggested as a possible underlying pathophysiologic mechanism in functional dyspepsia. However, the cortical regions activated by distention of the proximal stomach have not been identified. The aim of this study was to investigate regional brain activation during painful and nonpainful proximal gastric distention in humans.

Combination therapy with hydrocortisone and fludrocortisone does not improve symptoms in chronic fatigue syndrome: a randomized, placebo-controlled, double-blind, crossover study.

Purpose: Chronic fatigue syndrome has been associated with decreased function of the hypothalamic-pituitary-adrenal axis. Although neurally mediated hypotension occurs more frequently in patients with chronic fatigue syndrome than in controls, attempts to alleviate symptoms by administration of hydrocortisone or fludrocortisone have not been successful. The purpose of this study was to investigate the effect of combination therapy (5 mg/d of hydrocortisone and 50 microg/d of 9-alfa-fludrocortisone) on fatigue and well-being in chronic fatigue syndrome.

Heterogeneity of symptom pattern, psychosocial factors, and pathophysiological mechanisms in severe functional dyspepsia.

Background & Aims: Categorization of functional dyspepsia into subgroups is based on expert opinion according to (dominant) symptoms or on underlying pathophysiological mechanisms. We used an evidence-based approach to the determination of subtypes of functional dyspepsia.

Methods: Consecutive functional dyspepsia patients were recruited from a tertiary referral center.