A large-scale genome-wide gene expression analysis in peripheral blood identifies very few differentially expressed genes related to antidepressant treatment and response in patients with major depressive disorder

A better understanding of the biological factors underlying antidepressant treatment in patients with major depressive disorder (MDD) is needed. We perform gene expression analyses and explore sources of variability in peripheral blood related to antidepressant treatment and treatment response in patients suffering from recurrent MDD at baseline and after 8 weeks of treatment. The study includes 281 patients, which were randomized to 8 weeks of treatment with vortioxetine (N = 184) or placebo (N = 97). To our knowledge, this is the largest dataset including both gene expression in blood and placebo-controlled treatment response measured by a clinical scale in a randomized clinical trial. We identified three novel genes whose RNA expression levels at baseline and week 8 are significantly (FDR < 0.05) associated with treatment response after 8 weeks of treatment. Among these genes were SOCS3 (FDR = 0.0039) and PROK2 (FDR = 0.0028), which have previously both been linked to depression. Downregulation of these genes was associated with poorer treatment response. We did not identify any genes that were differentially expressed between placebo and vortioxetine groups at week 8 or between baseline and week 8 of treatment. Nor did we replicate any genes identified in previous peripheral blood gene expression studies examining treatment response. Analysis of genome-wide expression variability showed that type of treatment and treatment response explains very little of the variance, a median of <0.0001% and 0.05% in gene expression across all genes, respectively. Given the relatively large size of the study, the limited findings suggest that peripheral blood gene expression might not be the best approach to explore the biological factors underlying antidepressant treatment.Subject terms: Predictive markers, Depression     

Seroepidemiology of hepatitis E in patients on haemodialysis in Croatia

International Urology and Nephrology - Data on the seroprevalence of hepatitis E virus (HEV) in heamodialysis (HD) patients are conflicting, ranging from 0 to 44%. The aim of this study was to...     

Contrast agents in abdominal imaging: current and future directions

Magnetic resonance imaging is an established imaging method for the evaluation of the abdomen. Accurate assessment of the liver, spleen, pancreas, bile ducts, vascular structures, and retroperitoneal organs (eg, the kidneys, the collecting system, and the adrenals) are possible on MR imaging. The intravenous administration of MR contrast agents can frequently improve the examination and provide more specific diagnoses. The advent of more specific, "hepatobiliary" contrast agents has further improved the differential diagnostic process, particularly for MR imaging of the liver. The availability of orally administered MR contrast agents has further extended the range of abdominal applications, making MR imaging of the small bowel and the colon established imaging procedures.     

A prospective controlled trial on effect of percutaneous transluminal angioplasty on functioning arteriovenous fistulae survival

Balloon angioplasty (PTA) is an established treatment modality for stenosis in dysfunctional arteriovenous fistulae (AVF), although most studies showing efficacy have been retrospective, uncontrolled, and nonrandomized. In addition, it is unknown whether correction of stenosis not associated with significant hemodynamic, functional, and clinical abnormality may improve survival in AVF. This study was a prospective controlled open trial to evaluate whether prophylactic PTA of stenosis not associated with access dysfunction improves survival in native, virgin, radiocephalic forearm AVF. Sixty-two stenotic, functioning AVF, i.e., able to provide adequate dialysis, were enrolled in the study: 30 were allocated to control and 32 to PTA. End points of the study were either AVF thrombosis or surgical revision due to reduction in delivered dialysis dose. Kaplan-Meier analysis showed that PTA improved AVF functional failure-free survival rates (P = 0.012) with a fourfold increase in median survival and a 2.87-fold decrease in risk of failure. Cox proportional hazard model identified PTA as the only variable associated with outcome (P = 0.012). PTA induced an increase in access blood flow rate (Qa) by 323 (236 to 445) ml/min (P < 0.001), suggesting that improved AVF survival is the result of increased Qa. PTA was also associated with a significant decrease in access-related morbidity by approximately halving the risk of hospitalization, central venous catheterization, and thrombectomy (P < 0.05). This study shows that prophylactic PTA of stenosis in functioning forearm AVF improves access survival and decreases access-related morbidity, supporting the usefulness of preventive correction of stenosis before the development of access dysfunction. It also strongly supports surveillance program for early detection of stenosis.     

Gentamicin-induced hair cell death is not dependent on the apoptosis receptor Fas

OBJECTIVES/HYPOTHESIS: The hair cells are the most vulnerable elements in the cochlea, and damage to them is the most common cause of sensorineural hearing loss. Understanding the intracellular events that lead to the death of hair cells is a key to developing protective strategies. The Fas death receptor-mediated apoptotic pathway is well studied and plays an important role in the elimination of damaged cells in a number of different cellular systems. We have studied the role of the Fas receptor in aminoglycoside-mediated toxicity in vitro. We employed the MRL/MpJ-Fas mouse, which does not express a functional Fas receptor. STUDY DESIGN: Response of Fas-deficient hair cells to gentamicin was compared with the response of normal hair cells in vitro. METHODS: Basal turn organ of Corti explants from p3-5 mice were maintained in tissue culture and treated with gentamicin for 72 hours. The explants were fixed and were stained with phalloidin, and counting was performed. RESULTS: There was no difference in hair cell loss between Fas mutant mice and control MRL/MpJ mice with a functional Fas receptor. CONCLUSION: The gentamicin-mediated hair cell death is not dependent on a functional Fas receptor.     

Neuroimaging findings in malignant infantile osteopetrosis due to OSTM1 mutations

Malignant infantile osteopetrosis (MIOP) is a rare autosomal recessive disorder of bone resorption characterized by early bone marrow failure, proneness to fractures, and visual deterioration, variably associated with impairments of other cranial nerves due to narrowing of skull base foramina. About 10% of patients with MIOP show severe neurological involvement, which contraindicates bone marrow transplantation. We report on a 12-month-old female with recessive OSMT1 mutations and neuroimaging findings suggesting a neurodegenerative storage disorder.     

Whole-body magnetic resonance angiography with blood-pool agents

Although often asymptomatic, peripheral arterial disease (PAD) is associated with significant morbidity in a large proportion of patients. Atherosclerosis is the underlying pathology in many instances, involving the whole arterial tree. Whole-body magnetic resonance angiography (MRA) permits rapid, non-invasive and accurate evaluation of the entire vascular system and can be used for both diagnostic purposes and monitoring of vascular involvement in diseases such as diabetes, Marfan's syndrome and Takayasu arteritis. MRA has been used successfully in the identification of high-grade stenosis in PAD, abnormalities of the ileocaval veins and carotid plaque imaging. Carotid disease is significantly correlated with severe coronary artery disease and renal artery atherosclerosis. Symptomatic lesions in one vascular bed are often related to additional asymptomatic atherosclerotic lesions in other vascular regions. MRA may be advantageous over computed tomographic angiography because it can be performed with contrast media virtually devoid of serious toxicity and without utilization of ionizing radiation. Display of the entire arterial vasculature can be achieved in <90 s, with excellent sensitivity and specificity. Recent technological advances, such as parallel imaging and the implementation of dedicated matrix coils, have further increased image quality, and in combination with the blood-pool contrast agents, such as gadofosveset trisodium (Vasovist, Bayer Schering Pharma AG, Berlin, Germany), extended imaging time, higher spatial resolution and larger anatomical coverage can be achieved.     

Coagulation defects in neonates during cardiopulmonary bypass.

We examined components of the coagulation system in 30 neonates (age, 1 to 30 days) undergoing deep hypothermic cardiopulmonary bypass (CPB). A coagulation profile consisting of activated clotting time; prothrombin time; partial thromboplastin time; factors II, V, VII, VIII, IX, X, and I (fibrinogen); antithrombin III; platelet count; and heparin levels was evaluated before bypass, at three intervals during bypass (1 minute after initiation of bypass, stable hypothermic CPB, warm CPB), after weaning from CPB and administration of protamine, and 2 to 3 hours after skin closure. The initiation of CPB resulted in a 50% decrease in circulating coagulation factors and antithrombin III levels. Platelet counts were reduced by 70% with CPB initiation. Neither deep hypothermic temperatures nor prolonged exposure to extracorporeal surfaces had any additional effect on the coagulation profiles. This suggests that the coagulation system of a neonate undergoing CPB is profoundly and globally effected by hemodilution. We believe that treatment of post-CPB coagulopathy in neonates must address these global deficits.