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Introduction Chronic use of methamphetamine induces neuropsychological deficits and neurochemical changes in frontostriatal regions. This study aimed to examine the relationship between brain metabolites alterations in frontostriatal regions and neuropsychological deficits in patients with methamphetamine use disorder. Method A total of 30 methamphetamine users and 20 control participants were selected and a battery of standardized executive function, attention, and memory tasks, including the Wisconsin Card Sorting Test, Stroop Test, and Wechsler Memory Scale, was administered to them. Proton-Magnetic resonance spectroscopy (H-MRS) of N-Acetylaspartate/Creatine (NAA/Cr), Choline/Creatine (Cho/Cr), and glutamate + glutamine/creatine (Glx/Cr) in dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and basal ganglia (BG) were also undertaken. Results Current findings indicated that there were significant differences between two groups in metabolite ratios including NAA/Cr, Cho/Cr, and Glx/Cr in three areas, except for Glx/Cr in BG. Moreover, compared to healthy controls, methamphetamine users showed poorer performance in all neuropsychological tests. Finally, a significant relationship was found between regional metabolites alterations, particularly in the ACC, and neuropsychological deficits in methamphetamine users. Conclusions In addition to neurochemical changes and neuropsychological deficits in patients with methamphetamine use disorder, current results highlighted the relationship between these changes in DLPFC, ACC, and BG with cognitive deficits in methamphetamine users. [ABSTRACT FROM AUTHOR]

Abstract Background The pathogenesis and cardiovascular impact of type 2 diabetes (T2D) may be different in South Asians compared with other ethnic groups. The phenotypic characterization of diabetic cardiomyopathy remains debated and little is known regarding differences in T2D-related cardiovascular remodeling across ethnicities. We aimed to characterize the differences in left ventricular (LV) diastolic and systolic function, LV structure, myocardial tissue characteristics and aortic stiffness between T2D patients and controls and to assess the differences in T2D-related cardiovascular remodeling between South Asians and Europeans. Methods T2D patients and controls of South Asian and European descent underwent 3 Tesla cardiovascular magnetic resonance imaging (CMR) and cardiac proton-magnetic resonance spectroscopy (1H-MRS). Differences in cardiovascular parameters between T2D patients and controls were examined using ANCOVA and were reported as mean (95% CI). Ethnic group comparisons in the association of T2D with cardiovascular remodeling were made by adding the interaction term between ethnicity and diabetes status to the model. Results A total of 131 individuals were included (54 South Asians [50.1 ± 8.7 years, 33% men, 33 patients vs. 21 controls) and 77 Europeans (58.8 ± 7.0 years, 56% men, 48 patients vs. 29 controls)]. The ratio of the transmitral early and late peak filling rate (E/A) was lower in T2D patients compared with controls, in South Asians [− 0.20 (− 0.36; − 0.03), P = 0.021] and Europeans [− 0.20 (− 0.36; − 0.04), P = 0.017], whereas global longitudinal strain and aortic pulse wave velocity were similar. South Asian T2D patients had a higher LV mass [+ 22 g (15; 30), P

Pavlovian conditioned approach ( PCA) is a behavioral procedure that can be used to assess individual differences in the addiction vulnerability of drug-naïve rats and identify addiction vulnerability factors. Using proton magnetic resonance spectroscopy (1H- MRS) ex vivo, we simultaneously analyzed concentrations of multiple neurochemicals throughout the mesocorticolimbic system 2 weeks after PCA training in order to identify potential vulnerability factors to addiction in drug-naïve rats for future investigations. Levels of myo-inositol (Ins), a 1H- MRS-detectable marker of glial activity/proliferation, were increased in the nucleus accumbens ( NAc) and ventral hippocampus, but not dorsal hippocampus or medial prefrontal cortex, of sign-trackers compared to goal-trackers or intermediate responders. In addition, Ins levels positively correlated with PCA behavior in the NAc and ventral hippocampus. Because the sign-tracker phenotype is associated with increased drug-seeking behavior, these results observed in drug-naïve rats suggest that alterations in glial activity/proliferation within these regions may represent an addiction vulnerability factor. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular complications of obesity and diabetes are major health problems. Assessing their development, their link with ectopic fat deposition and their flexibility with therapeutic intervention is essential. The aim of this study was to longitudinally investigate cardiac alterations and ectopic fat accumulation associated with diet-induced obesity using multimodal cardiovascular magnetic resonance (CMR) in mice. The second objective was to monitor cardiac response to exendin-4 (GLP-1 receptor agonist). Methods: Male C57BL6R mice subjected to a high fat (35 %) high sucrose (34 %) (HFHSD) or a standard diet (SD) during 4 months were explored every month with multimodal CMR to determine hepatic and myocardial triglyceride content (HTGC, MTGC) using proton MR spectroscopy, cardiac function with cine cardiac MR (CMR) and myocardial perfusion with arterial spin labeling CMR. Furthermore, mice treated with exendin-4 (30 µg/kg SC BID) after 4 months of diet were explored before and 14 days post-treatment with multimodal CMR. Results: HFHSD mice became significantly heavier (+33 %) and displayed glucose homeostasis impairment (1-month) as compared to SD mice, and developed early increase in HTGC (1 month, +59 %) and MTGC (2-month, +63 %). After 3 months, HFHSD mice developed cardiac dysfunction with significantly higher diastolic septum wall thickness (sWtnD) (1.28 ± 0.03 mm vs. 1.12 ± 0.03 mm) and lower cardiac index (0.45 ± 0.06 mL/min/g vs. 0.68 ± 0.07 mL/min/g, p = 0.02) compared to SD mice. A significantly lower cardiac perfusion was also observed (4 months:7.5 ± 0.8 mL/g/min vs. 10.0 ± 0.7 mL/g/min, p = 0.03). Cardiac function at 4 months was negatively correlated to both HTGC and MTGC (p < 0.05). 14-day treatment with Exendin-4 (Ex-4) dramatically reversed all these alterations in comparison with placebo-treated HFHSD. Ex-4 diminished myocardial triglyceride content (-57.8 ± 4.1 %), improved cardiac index (+38.9 ± 10.9 %) and restored myocardial perfusion (+52.8 ± 16.4 %) under isoflurane anesthesia. Interestingly, increased wall thickness and hepatic steatosis reductions were independent of weight loss and glycemia decrease in multivariate analysis (p < 0.05). Conclusion: CMR longitudinal follow-up of cardiac consequences of obesity and diabetes showed early accumulation of ectopic fat in mice before the occurrence of microvascular and contractile dysfunction. This study also supports a cardioprotective effect of glucagon-like peptide-1 receptor agonist. [ABSTRACT FROM AUTHOR]

Abstract: Gamma-aminobutyric acid (GABA) is the major inhibitory amino acid neurotransmitter in the brain and is primarily responsible for modulating excitatory tone. Clinical neuroimaging studies show decreased GABA levels in the anterior cingulate of patients with mood disorders, including major depressive disorder. Chronic unpredictable stress (CUS) is an animal model thought to mimic the stressful events that may precipitate clinical depression in humans. In this study male Sprague–Dawley rats were subjected to a modified CUS paradigm that used a random pattern of unpredictable stressors twice daily for 10days to explore the early developmental stages of depression-like endophenotypes. Control rats were handled daily for 10days. Some rats from each treatment group received an injection of ketamine (40mg/kg) after the final stressor. One day following the final stressor rats were tested for behavioral effects in the forced swim test and then euthanized to collect trunk blood and anterior cingulate brain samples. GABA levels were measured in anterior cingulate samples ex vivo using proton magnetic resonance spectroscopy (1H-MRS) at 11.7T. Animals subjected to CUS had lower body weights, higher levels of blood corticosterone, and increased immobility in the forced swim test; all of which suggest that the stress paradigm induced a depression-like phenotype. GABA levels in the anterior cingulate were significantly increased in the stressed animals compared to controls. Administration of ketamine on the last day of treatment blunted the depression-like behavior and increased GABA levels in the anterior cingulate following CUS. These data indicate that stress disrupts GABAergic signaling, which may over time lead to symptoms of depression and ultimately lower basal levels of cortical 1H-MRS GABA that are seen in humans with depression. Furthermore, the data suggests that ketamine modulates cortical GABA levels as a mechanism of its antidepressant activity. [Copyright &y& Elsevier]

Background: The pathogenesis and cardiovascular impact of type 2 diabetes (T2D) may be different in South Asians compared with other ethnic groups. The phenotypic characterization of diabetic cardiomyopathy remains debated and little is known regarding differences in T2D-related cardiovascular remodeling across ethnicities. We aimed to characterize the differences in left ventricular (LV) diastolic and systolic function, LV structure, myocardial tissue characteristics and aortic stiffness between T2D patients and controls and to assess the differences in T2D-related cardiovascular remodeling between South Asians and Europeans. Methods: T2D patients and controls of South Asian and European descent underwent 3 Tesla cardiovascular magnetic resonance imaging (CMR) and cardiac proton-magnetic resonance spectroscopy (1H-MRS). Differences in cardiovascular parameters between T2D patients and controls were examined using ANCOVA and were reported as mean (95% CI). Ethnic group comparisons in the association of T2D with cardiovascular remodeling were made by adding the interaction term between ethnicity and diabetes status to the model. Results: A total of 131 individuals were included (54 South Asians [50.1 ± 8.7 years, 33% men, 33 patients vs. 21 controls) and 77 Europeans (58.8 ± 7.0 years, 56% men, 48 patients vs. 29 controls)]. The ratio of the transmitral early and late peak filling rate (E/A) was lower in T2D patients compared with controls, in South Asians [− 0.20 (− 0.36; − 0.03), P = 0.021] and Europeans [− 0.20 (− 0.36; − 0.04), P = 0.017], whereas global longitudinal strain and aortic pulse wave velocity were similar. South Asian T2D patients had a higher LV mass [+ 22 g (15; 30), P < 0.001] (P for interaction by ethnicity = 0.005) with a lower extracellular volume fraction [− 1.9% (− 3.4; − 0.4), P = 0.013] (P for interaction = 0.114), whilst European T2D patients had a higher myocardial triglyceride content [+ 0.59% (0.35; 0.84), P = 0.001] (P for interaction = 0.002) than their control group. Conclusions: Diabetic cardiomyopathy was characterized by impaired LV diastolic function in South Asians and Europeans. Increased LV mass was solely observed among South Asian T2D patients, whereas differences in myocardial triglyceride content between T2D patients and controls were only present in the European cohort. The diabetic cardiomyopathy phenotype may differ between subsets of T2D patients, for example across ethnicities, and tailored strategies for T2D management may be required. [ABSTRACT FROM AUTHOR]

Background & Aims: Healthy lifestyle is the most important management of non-alcoholic fatty liver disease (NAFLD). This study aimed at assessing the efficacy of a community-based lifestyle modification programme in the remission of NAFLD., Methods: This was a parallel group, superiority, randomized controlled trial. 154 adults with NAFLD identified during population screening were randomized to participate in a dietitian-led lifestyle modification programme at 2 community centres or receive usual care for 12 months. The primary outcome was remission of NAFLD at month 12 as evidenced by intrahepatic triglyceride content (IHTG) of less than 5% by proton-magnetic resonance spectroscopy., Results: 74 patients in the intervention group and 71 patients in the control group completed all study assessments. In an intention-to-treat analysis of all 154 patients, 64% of the patients in the intervention group and 20% in the control group achieved remission of NAFLD (difference between groups 44%; 95% CI 30-58%; p<0.001). The mean (SD) changes in IHTG from baseline to month 12 were -6.7% (6.1%) in the intervention group and -2.1% (6.4%) in the control group (p<0.001). Body weight decreased by 5.6 (4.4) kg and 0.6 (2.5) kg in the two groups, respectively (p<0.001). While 97% of patients with weight loss of more than 10% had remission of NAFLD, 41% of those with weight loss of 3.0-4.9% could also achieve the primary outcome., Conclusions: The community-based lifestyle modification programme is effective in reducing and normalizing liver fat in NAFLD patients., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)