Electrophysiological and behavioral effects of unilateral and bilateral rTMS; A randomized clinical trial on rumination and depression.

BACKGROUND: Rumination is significantly frequent in major depressive disorder (MDD). However, not a lot of studies have investigated the effects of repetitive transcranial magnetic stimulation (rTMS) on rumination. METHODS: 61 participants with a minimum Hamilton Depression Rating Scale (HAM-D) score of 20 were randomly assigned to sham, bilateral stimulation (BS) or unilateral stimulation (US) groups. EEG, The Ruminative Response Scale (RRS), and HAM-D were administered before and after the 20 sessions of rTMS. Phase locked values (PLV) were calculated as a measure of connectivity. RESULTS: There was a significant decrease in HAM-D scores in both BS and US. In responders, BS and US differed significantly in RRS total scores, with greater reduction in BS. PLV significantly changed in the default mode network (DMN) in delta, theta, alpha, and beta in BS, in responders of which PLV decreased in the DMN in beta and gamma. Positive correlations between PLV and brooding in delta and theta, and negative correlations between PLV and reflection were found in theta, alpha, and beta. In US, connectivity in the DMN increased in beta, and PLV increased in theta and beta, and decreased in alpha and beta in its responders. Positive correlations between PLV and brooding in the delta and theta, as well as negative correlations between PLV and reflection in theta were observed in the DMN. CONCLUSION: US and BS resulted in different modulations in the DMN, however, both could alleviate both rumination and depression. Reductions in the beta and alpha frequency bands in the DMN can be considered as potential EEG-based markers of response to bilateral and unilateral rTMS, respectively.

Severe asymptomatic non-alcoholic fatty liver disease in routine diabetes care; a multi-disciplinary team approach to diagnosis and management.

OBJECTIVES: To prospectively use a non-invasive algorithm to identify asymptomatic, advanced non-alcoholic fatty liver disease (NAFLD) in a secondary care diabetes clinic and to determine the short-term effect of a multi-disciplinary team (MDT) approach in a liver clinic. RESEARCH DESIGN AND METHODS: NAFLD Fibrosis Score (NFS) was calculated in 64 asymptomatic patients with type 2 diabetes. Advanced fibrosis was identified using transient elastography and confirmed with liver biopsy. In a subsequent retrospective study, 95 patients newly referred to the NAFLD MDT clinic were investigated and the impact of the MDT approach assessed. RESULTS: 25/64 (39.0%) of patients with diabetes had a low NFS (<-1.455). 39/64 (61.0%) patients had a high or indeterminate NFS and were referred for review in the NAFLD MDT clinic, of which 23/39 attended for assessment. 19/23 (82.6%) were diagnosed with NAFLD, of which 6/19 (31.6%) patients had a positive transient elastography (≥8 kPa). Liver biopsy confirmed advanced fibrosis in 5/6 cases, with moderate fibrosis in 1 case. In the retrospective study, 65/95 (68.4%) new referrals to the NAFLD MDT clinic had a diagnosis of NAFLD. Over a median 98 days (IQR 70-182) follow-up, there was a significant improvement in weight (-0.8 kg; P = 0.024), total cholesterol (-0.2 mmol/L; P = 0.044), ALT (alanine transmaminase, -12.5 IU/L; P < 0.001) and GGT (gammu-glutamyl transferase, -13.0 IU/L; P < 0.0001). 7/28 (25%) of patients with diabetes achieved >5% weight loss. CONCLUSIONS: A significant proportion of asymptomatic patients attending type 2 diabetes clinics have undiagnosed advanced NAFLD fibrosis. An MDT approach to NAFLD results in short-term improvements in metabolic and liver parameters.

Development of a novel large animal model of ischemic heart failure using autologous platelet aggregates.

BACKGROUND: Current animal models of heart failure lack the biomass of thrombus that occurs in patients undergoing myocardial infarction. We propose a novel animal model of ischemic cardiomyopathy developed by sequential direct injections of autologous platelet aggregates into the coronary circulation resulting in development of ischemic cardiac insufficiency. METHODS: Autologous platelets from adult sheep were isolated and aggregated. Aggregated platelets were then injected into the coronary circulation of anesthetized animals under fluoroscopic guidance. Troponin I levels were monitored for first three days after embolization to validate cardiac tissue injury. Progression of heart failure was corroborated by monitoring changes in echo-based assessment of ejection fraction and left ventricular end-systolic and end-diastolic dimensions. Thrombus-based obstruction of coronary artery was confirmed with histopathology review by mepacrine labeling of pre-aggregated platelets. RESULTS: All experimental animals developed heart failure-like cardiac insufficiency confirmed by elevated levels of troponin I and associated with significant drop in the ejection fraction. CONCLUSIONS: Sequential injections of aggregated platelets into coronary circulation lead to progressive development of ischemic cardiac insufficiency. This phenomenon seems to mimic development of ischemic heart failure seen in human patients and opens multiple research opportunities to fill the existing gap between basic research and clinical practice.