Burden of fatty liver and hepatic fibrosis in persons with HIV: A diverse cross-sectional US multicenter study.

BACKGROUND AIMS: The current prevalence of fatty liver disease (FLD) due to alcohol-associated (AFLD) and nonalcoholic (NAFLD) origins in US persons with HIV (PWH) is not well defined. We prospectively evaluated the burden of FLD and hepatic fibrosis in a diverse cohort of PWH. APPROACH RESULTS: Consenting participants in outpatient HIV clinics in 3 centers in the US underwent detailed phenotyping, including liver ultrasound and vibration-controlled transient elastography for controlled attenuation parameter and liver stiffness measurement. The prevalence of AFLD, NAFLD, and clinically significant and advanced fibrosis was determined. Univariate and multivariate logistic regression models were used to evaluate factors associated with the risk of NAFLD. Of 342 participants, 95.6% were on antiretroviral therapy, 93.9% had adequate viral suppression, 48.7% (95% CI 43%-54%) had steatosis by ultrasound, and 50.6% (95% CI 45%-56%) had steatosis by controlled attenuation parameter ≥263 dB/m. NAFLD accounted for 90% of FLD. In multivariable analysis, old age, higher body mass index, diabetes, and higher alanine aminotransferase, but not antiretroviral therapy or CD4 + cell count, were independently associated with increased NAFLD risk. In all PWH with fatty liver, the frequency of liver stiffness measurement 8-12 kPa was 13.9% (95% CI 9%-20%) and ≥12 kPa 6.4% (95% CI 3%-11%), with a similar frequency of these liver stiffness measurement cutoffs in NAFLD. CONCLUSIONS: Nearly half of the virally-suppressed PWH have FLD, 90% of which is due to NAFLD. A fifth of the PWH with FLD has clinically significant fibrosis, and 6% have advanced fibrosis. These data lend support to systematic screening for high-risk NAFLD in PWH.

A randomized clinical trial of the efficacy and safety of sitagliptin as initial oral therapy in youth with type 2 diabetes.

OBJECTIVE: To assess the efficacy and safety of DPP-4 inhibition with sitagliptin in youth with type 2 diabetes (T2D). STUDY DESIGN: This was a 54-week, double-blind, randomized, controlled clinical trial evaluating the safety and efficacy of DPP-4 inhibition with sitagliptin 100 mg once daily as initial oral therapy in youth with T2D. The 190 participants, aged 10-17 years, had HbA1c 6.5%-10% (7.0%-10% if on insulin). All were negative for pancreatic autoantibodies and overweight/obese at screening or diagnosis. The trial was placebo controlled for the first 20 weeks, after which metformin replaced placebo. The primary efficacy endpoint was change from baseline in HbA1c at Week 20. RESULTS: Treatment groups were well balanced at baseline (mean ± SD HbA1c = 7.5% ± 1.0, BMI percentile = 97.1% ± 6.8, age = 14.0 years ± 2.0 [57.4% <15], 60.5% female). At Week 20, least squares mean changes from baseline in HbA1c were -0.01% (sitagliptin) and 0.18% (placebo); between-group difference (95% CI) = -0.19% (-0.68, 0.30), p = 0.448. At Week 54, the changes in HbA1c were 0.45% (sitagliptin) and -0.11 (placebo/metformin). There were no notable between-group differences in the adverse event profiles through Week 54. CONCLUSIONS: DPP-4 inhibition with sitagliptin did not provide significant improvement in glycemic control. In this study, sitagliptin was generally well tolerated with a safety profile similar to that reported in adults. (ClinicalTrials.gov: NCT01485614; EudraCT: 2011-002528-42).

Efficacy and safety of the addition of sitagliptin to treatment of youth with type 2 diabetes and inadequate glycemic control on metformin without or with insulin.

OBJECTIVE: To assess the efficacy and safety of sitagliptin in youth with type 2 diabetes (T2D) inadequately controlled with metformin ± insulin. STUDY DESIGN: Data were pooled from two 54-week, double-blind, randomized, placebo-controlled studies of sitagliptin 100 mg daily or placebo added onto treatment of 10- to 17-year-old youth with T2D and inadequate glycemic control on metformin ± insulin. Participants (N = 220 randomized and treated) had HbA1c 6.5%-10% (7.0%-10% if on insulin), were overweight/obese at screening or diagnosis and negative for pancreatic autoantibodies. The primary endpoint was change from baseline in HbA1c at Week 20. RESULTS: Treatment groups were well balanced at baseline (mean HbA1c = 8.0%, BMI = 30.9 kg/m2 , age = 14.4 years [44.5% <15], 65.9% female). The dose of background metformin was >1500 mg/day for 71.8% of participants; 15.0% of participants were on insulin therapy. At Week 20, LS mean changes from baseline (95% CI) in HbA1c for sitagliptin/metformin and placebo/metformin were -0.58% (-0.94, -0.22) and -0.09% (-0.43, 0.26), respectively; difference = -0.49% (-0.90, -0.09), p = 0.018; at Week 54 the LS mean (95% CI) changes were 0.35% (-0.48, 1.19) and 0.73% (-0.08, 1.54), respectively. No meaningful differences between the adverse event profiles of the treatment groups emerged through Week 54. CONCLUSIONS: These results do not suggest that addition of sitagliptin to metformin provides durable improvement in glycemic control in youth with T2D. In this study, sitagliptin was generally well tolerated with a safety profile similar to that reported in adults. (ClinicalTrials.gov: NCT01472367, NCT01760447; EudraCT: 2011-002529-23/2014-003583-20, 2012-004035-23).

Advanced Hodgkin lymphoma in the East of England: a 10-year comparative analysis of outcomes for real-world patients treated with ABVD or escalated-BEACOPP, aged less than 60 years, compared with 5-year extended follow-up from the RATHL trial.

Treatment with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or escalated(e)-BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) remains the international standard of care for advanced-stage classical Hodgkin lymphoma (HL). We performed a retrospective, multicentre analysis of 221 non-trial ("real-world") patients, aged 16-59 years, diagnosed with advanced-stage HL in the Anglia Cancer Network between 2004 and 2014, treated with ABVD or eBEACOPP, and compared outcomes with 1088 patients in the Response-Adjusted Therapy for Advanced Hodgkin Lymphoma (RATHL) trial, aged 18-59 years, with median follow-up of 87.0 and 69.5 months, respectively. Real-world ABVD patients (n=177) had highly similar 5-year progression-free survival (PFS) and overall survival (OS) compared with RATHL (PFS 79.2% vs 81.4%; OS 92.9% vs 95.2%), despite interim positron-emission tomography-computed tomography (PET/CT)-guided dose-escalation being predominantly restricted to trial patients. Real-world eBEACOPP patients (n=44) had superior PFS (95.5%) compared with real-world ABVD (HR 0.20, p=0.027) and RATHL (HR 0.21, p=0.015), and superior OS for higher-risk (international prognostic score ≥3 [IPS 3+]) patients compared with real-world IPS 3+ ABVD (100% vs 84.5%, p=0.045), but not IPS 3+ RATHL patients. Our data support a PFS, but not OS, advantage for patients with advanced-stage HL treated with eBEACOPP compared with ABVD and suggest higher-risk patients may benefit disproportionately from more intensive therapy. However, increased access to effective salvage therapies might minimise any OS benefit from reduced relapse rates after frontline therapy.

Higher Monocyte Count is Associated with 30-Day Case Fatality in Intracerebral Hemorrhage.

BACKGROUND: Previous studies have suggested that elevated neutrophils, monocytes, and neutrophil-to-lymphocyte ratio (NLR) may be associated with poor outcomes in intracerebral hemorrhage (ICH). We sought to determine whether white blood cell (WBC) types were independently associated with poor outcome in ICH in a large cohort. METHODS: We performed a retrospective study of primary ICH at two academic centers. Cases were identified via ICD-9 code and verified via physician review. We included only those patients with WBC types obtained within 24 h of ICH onset. RESULTS: We identified 593 patients with primary ICH and WBC differentials in the first 24 h. Independent factors (OR, 95% CI) associated with 30-day case fatality were age > 80 (2.4 (1.4, 4.2)), p = 0.0023; NIHSS greater than median (3.9 (2.4, 6.3)), p < 0.0001; ICH volume quartiles (Q1: ref, Q2: 1.5 (0.7, 3.0), Q3: 3.2 (1.6, 6.6), Q4: 11.9 (5.3, 26.4)), p < 0.0001; non-lobar location (3.3 (1.9, 5.9)), p ≤ 0.0001; IVH (2.3 (1.4, 3.6)), p = 0.0005, monocytes greater than median (1.6 (1.0, 2.4)), p = 0.0457, and anticoagulant use (3.2 (1.8, 5.6)), p < 0.0001. Elevated NLR was not associated with higher case fatality. CONCLUSIONS: We found that elevated monocytes were independently associated with 30-day case fatality. Future studies will investigate whether there are subgroups of ICH patients, including those with particular blood or imaging biomarkers, in which WBC types might help predict poor outcome and provide targets for intervention.

The ENCOURAGE healthy families study: A comparative effectiveness trial to reduce risk for type 2 diabetes in mothers and children.

INTRODUCTION: Trials in adults have demonstrated that interventions targeting lifestyle are effective in preventing or delaying type 2 diabetes (T2D). To address this need in youth, we developed ENCOURAGE Healthy Families (ENCOURAGE), based on the US Diabetes Prevention Program (DPP). STUDY DESIGN: Here, we present results of the ENCOURAGE randomized, comparative effectiveness trial in which we evaluated ENCOURAGE delivered to (1) mothers only, and (2) mothers with added content delivered to their children. PARTICIPANTS: The study was performed in Indianapolis, IN, at an academic medical center and the YMCA; December 2012 to April 2016. Women with a history of gestational diabetes mellitus (GDM) or prediabetes with children aged 8 to 15 years enrolled (n = 128). OUTCOME MEASURES: Outcomes were collected at baseline, postintervention (3 months), 6 and 12 months. The primary outcome was weight change at 3 months in adults; secondary outcomes included glycosylated hemoglobin (HbA1c), lipids, and blood pressure. RESULTS: In neither program did mothers' weight change. HbA1c decreased at 3 months in both groups (mothers only=-0.09%, P = .019; mothers and children=-0.11%, P = .003). Participating children had a reduction in body mass index (BMI) percentile at 3 (-1.77, P = .014), 6 (-3.0, P = .002), and 12 months (-2.91, P = .004). HbA1c decreased in children in both groups (mothers only = -0.12% at 3 months [P < .0001], -0.13% at 6 months [P < .001], and -0.07% at 12 months [P = .001]; mothers and children = -0.08% at 3 months (P < .0001), -0.07% at 6 months (P = .0004), and -0.04% at 12 months (P = .03). CONCLUSION: ENCOURAGE was beneficial for reducing BMI percentile in participating children.

Constrained Photophysics of 5,7-dimethoxy-2,3,4,9-tetrahydro-1H-carbazol-1-one in the Bioenvironment of Serum Albumins: A Spectroscopic Endeavour Supported by Molecular Docking Analysis.

This paper vividly indicates that steady state as well as time-resolved fluorescence techniques can serve as highly sensitive monitors to explore the interactions of 5,7-dimethoxy-2,3,4,9-tetrahydro-1H-carbazol-1-one with model transport proteins, bovine serum albumin (BSA) and human serum albumin (HSA). Besides these, we have used fluorescence anisotropy study to assess the degree of restrictions imparted by the micro-environments of serum albumins. Again, to speculate the triplet excited state interaction between such fluorophore and albumin proteins (BSA& HSA), laser flash-photolysis experiments have been carried out. Molecular docking experiments have also been performed to support the conclusions obtained from steady state experiments.

Prophylactic Anticonvulsants in Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Prophylactic anticonvulsants are routinely prescribed in the acute setting for intracerebral hemorrhage (ICH) patients, but some studies have reported an association with worse outcomes. We sought to characterize the prevalence and predictors of prophylactic anticonvulsant administration after ICH as well as guideline adherence. We also sought to determine whether prophylactic anticonvulsants were independently associated with poor outcome. METHODS: We performed a retrospective study of primary ICH in our two academic centers. We used a propensity matching approach to make treated and non-treated groups comparable. We conducted multiple logistic regression analysis to identify independent predictors of prophylactic anticonvulsant initiation and its association with poor outcome as measured by modified Rankin score. RESULTS: We identified 610 patients with primary ICH, of whom 98 were started on prophylactic anticonvulsants. Levetiracetam (97%) was most commonly prescribed. Age (OR 0.97, 95% CI 0.95-0.99, p < .001), lobar location (OR 2.94, 95% CI 1.76-4.91, p < .001), higher initial National Institutes of Health Stroke Scale (NIHSS) score (OR 2.31, 95% CI 1.40-3.79, p = .001), craniotomy (OR 3.06, 95% CI 1.51-6.20, p = .002), and prior ICH (OR 2.36, 95% CI 1.10-5.07, p = .028) were independently associated with prophylactic anticonvulsant initiation. Prophylactic anticonvulsant use was not associated with worse functional outcome [modified Rankin score (mRS) 4-6] at hospital discharge or with increased case-fatality. There was no difference in prescribing patterns after 2010 guideline publication. DISCUSSION: Levetiracetam was routinely prescribed following ICH and was not associated with worse outcomes. Future investigations should examine the effect of prophylactic levetiracetam on cost and neuropsychological outcomes as well as the role of continuous EEG in identifying subclinical seizures.

Comparison of Commercial and Self-Initiated Weight Loss Programs in People With Prediabetes: A Randomized Control Trial.

OBJECTIVES: To determine if a widely available weight-management program (Weight Watchers) could achieve sufficient weight loss in persons with prediabetes compared with a Diabetes Prevention Program-based individual counseling program supported by National Diabetes Education Program materials. METHODS: We conducted an individual, randomized intervention trial in Indianapolis, Indiana, in 2013 to 2014, in 225 persons with prediabetes. We compared the Weight Watchers weight-management program (n = 112) with Your Game Plan to Prevent Type 2 Diabetes, a program developed by the National Diabetes Education Program. Outcomes were weight and metabolic markers measured at baseline, 6 months, and 12 months. RESULTS: Intervention participants lost significantly more weight than controls at 6 months (5.5% vs 0.8%) and 12 months (5.5% vs 0.2%; both P < .001). The intervention group also had significantly greater improvements in hemoglobin A1c and high-density lipoprotein cholesterol level than did controls. CONCLUSIONS: A large weight-management program is effective for achieving lifestyle changes associated with diabetes prevention. Such programs could significantly increase the availability of diabetes prevention programs worldwide making an immediate and significant public health impact.

A Randomized Comparative Effectiveness Trial for Preventing Type 2 Diabetes.

OBJECTIVES: We evaluated the weight loss effectiveness of a YMCA model for the Diabetes Prevention Program (DPP) lifestyle intervention. METHODS: Between July 2008 and November 2010, we individually randomized 509 overweight or obese, low-income, nondiabetic adults with elevated blood glucose in Indianapolis, Indiana, to receive standard care plus brief lifestyle counseling or be offered a group-based YMCA adaptation of the DPP (YDPP). Primary outcome was mean weight loss difference at 12 months. In our intention-to-treat analyses, we used longitudinal linear or logistic regression, multiply imputing missing observations. We used instrumental variables regression to estimate weight loss effectiveness among participants completing 9 or more intervention lessons. RESULTS: In the YDPP arm, 161 (62.6%) participants attended ≥ 1 lesson and 103 (40.0%) completed 9 or more lessons. In intention-to-treat analysis, mean 12-month weight loss was 2.3 kilograms (95% confidence interval [CI] = 1.1, 3.4 kg) more for the YDPP arm than for standard care participants. In instrumental variable analyses, persons attending 9 or more lessons had a 5.3-kilogram (95% CI = 2.8, 7.9 kg) greater weight loss than did those with standard care alone. CONCLUSIONS: The YMCA model for DPP delivery achieves meaningful weight loss at 12 months among low-income adults.

Monitoring the Competence of a New Keto-tetrahydrocarbazole Based Fluorosensor Under Homogeneous, Micro-Heterogeneous and Serum Albumin Environments.

We present here a detailed photophysical study of a recently synthesised fluorophore 8-methyl-8,9-dihydro-5H-[1,3]dioxolo[4,5-b]carbazol-6(7H)-one. This is a synthetic precursor of bio-active carbazole skeleton Clausenalene. Spectroscopic investigation of the fluorophore has been carried out in different protic and aprotic solvents, as well as in binary solvent mixtures, using absorption, steady-state and time-resolved fluorescence techniques. This fluorophore is particularly responsive to the hydrogen bonding nature as well as polarity of the solvent molecules. When considered in micelles and ß-cyclodextrin, this behaves as a reporter of its immediate microenvironment. Steady state and time resolved fluorometric and circular dichroism techniques have been used to explore the binding interaction of the fluorophore with transport proteins, bovine serum albumin and human serum albumin. The probable binding sites of the fluorophore in the proteinous environments have been evaluated from fluorescence resonance energy transfer study. Laser flash photolysis experiments also have been performed to observe the triplet excited state interaction between the fluorophore and albumin proteins.

Effect of self-efficacy on weight loss: a psychosocial analysis of a community-based adaptation of the diabetes prevention program lifestyle intervention.

Objective. Weight loss is the most effective approach to reducing diabetes risk. It is a research priority to identify factors that may enhance weight loss success, particularly among those at risk for diabetes. This analysis explored the relationships between self-efficacy, weight loss, and dietary fat intake among adults at risk for developing type 2 diabetes. Methods. This pilot, site-randomized trial was designed to compare group-based Diabetes Prevention Program lifestyle intervention delivery by YMCA staff to brief counseling alone (control) in 92 adults at risk for diabetes (BMI ≥ 24 kg/m(2), ≥ 2 diabetes risk factors, and a random capillary blood glucose of 110-199 mg/dl). Self-efficacy was measured using the Weight Efficacy Lifestyle questionnaire. Data were collected at baseline, 6 months, and 12 months. A paired t test was used to determine within-group changes in self-efficacy and weight at 6 and 12 months. Using a fitted model, we estimated how much of an increase in self-efficacy was related to a 5% weight reduction at 6 and 12 months. Results. Self-efficacy was associated with a 5% reduction in baseline weight at 6 and 12 months but was not related to fat intake. Conclusion. These findings suggest that it is important to assess the level of self-efficacy when counseling adults at high risk for diabetes about weight loss. Certain aspects of self-efficacy seem to play a greater role, depending on the stage of weight loss.

Chronic lung disease and detection of pulmonary artery dilatation in high resolution computerized tomography of chest in chronic arsenic exposure.

Lung affection in chronic arsenicosis developing from chronic ingestion of arsenic contaminated groundwater has been known but little is known on its effect on pulmonary arterial system. A cross sectional study was carried out at two geographically similar areas and demographically similar populations with or without evidence of chronic arsenic exposure in West Bengal, India. The willing participants in both the groups with chronic respiratory symptoms were evaluated with High Resolution Computerized Tomography (HRCT) of Chest. Evaluation of High Resolution Computerized Tomography of chest followed clinical assessment of lung disease in194 and 196 subjects from the arsenic exposed and unexposed people; the former had a higher prevalence of cough OR(Odds Ratio) 3.23 (95% CI(Confidence Interval): 1.72-6.07) and shortness of breath OR1.76 (95% CI: 0.84-3.71), respectively. The arsenic exposed individuals showed higher score for bronchiectasis [mean ± SD(Standard Deviation)] as 2.41 ± 2.32 vs. 1.22 ± 1.48 (P <0.001), pulmonary artery branch dilatation (PAD) as 2.48 ± 2.33 vs. 0.78 ± 1.56, (P <0.001) and pulmonary trunk dilatation as 0.26 ± 0.45 vs. nil. Age-adjusted prevalence odds ratio (POR) for Pulmonary Artery Dilatation Found in HRCT comparing those exposed to arsenic (Group 1) to unexposed participants (Group 2) was found to be 6.98 (CI: 2.26-16.48). There was a strong dose-response relationship between the PAD (Pulmonary Artery Dilatation) and cumulative arsenic exposure. Pulmonary trunk and branch dilatation in chronic arsenicosis is a frequent abnormality seen in HRCT Chest of arsenicosis patients. The significance of such finding needs further investigation.

Dietary arsenic exposure with low level of arsenic in drinking water and biomarker: a study in West Bengal.

The authors investigated association of arsenic intake through water and diet and arsenic level in urine in people living in arsenic endemic region in West Bengal supplied with arsenic-safe water (<50 µg L(-1)). Out of 94 (Group-1A) study participants using water with arsenic level <50 µg L(-1), 72 participants (Group-1B) were taking water with arsenic level <10 µg L(-1). Multiple regressions analysis conducted on the Group-1A participants showed that daily arsenic dose from water and diet were found to be significantly positively associated with urinary arsenic level. However, daily arsenic dose from diet was found to be significantly positively associated with urinary arsenic level in Group-1B participants only, but no significant association was found with arsenic dose from water in this group. In a separate analysis, out of 68 participants with arsenic exposure through diet only, urinary arsenic concentration was found to correlate positively (r = 0.573) with dietary arsenic in 45 participants with skin lesion while this correlation was insignificant (r = 0.007) in 23 participants without skin lesion. Our study suggested that dietary arsenic intake was a potential pathway of arsenic exposure even where arsenic intake through water was reduced significantly in arsenic endemic region in West Bengal. Observation of variation in urinary arsenic excretion in arsenic-exposed subjects with and without skin lesion needed further study.

Gray and White Matter Voxel-Based Morphometry of Alzheimer's Disease With and Without Significant Cerebrovascular Pathologies.

Alzheimer's disease (AD) is the most common type of dementia, and AD individuals often present significant cerebrovascular disease (CVD) symptomology. AD with significant levels of CVD is frequently labeled mixed dementia (or sometimes AD-CVD), and the differentiation of these two neuropathologies (AD, AD-CVD) from each other is challenging, especially at early stages. In this study, we compared the gray matter (GM) and white matter (WM) volumes in AD (n = 83) and AD-CVD (n = 37) individuals compared with those of cognitively healthy controls (n = 85) using voxel-based morphometry (VBM) of their MRI scans. The control individuals, matched for age and sex with our two dementia groups, were taken from the ADNI. The VBM analysis showed widespread patterns of significantly lower GM and WM volume in both dementia groups compared to the control group (P < .05, family-wise error corrected). While comparing with AD-CVD, the AD group mainly demonstrated a trend of lower volumes in the GM of the left putamen and right hippocampus and WM of the right thalamus (uncorrected P < .005 with cluster threshold, K = 10). The AD-CVD group relative to AD tended to present lower GM and WM volumes, mainly in the cerebellar lobules and right brainstem regions, respectively (uncorrected P < .005 with cluster threshold, K = 10). Although finding a discriminatory feature in structural MRI data between AD and AD-CVD neuropathologies is challenging, these results provide preliminary evidence that demands further investigation in a larger sample size.

The Association between Sleep and Depression during Late Pregnancy and the Early Postpartum Period.

Objective To assess and correlate sleep quality and depressed mood symptoms in the late pregnancy and early postpartum periods. Study Design In a prospective pilot observational study, participants completed the Pittsburgh Sleep Quality Index (PSQI) and the Edinburgh Postnatal Depression Scale (EPDS) questionnaires at delivery, 1, and 2 months postpartum. Pearson's correlation coefficients and PROC MIXED function estimated overall correlation for repeated measures. Results Twenty-six women were enrolled with a mean gestational age at delivery of 38.4 (± 2.4) weeks. Sleep quality and mood data were available at the three time points for 24, 16, and 11 participants, respectively. Poor sleep scores were noted by 75.0, 87.5, and 72.7% of women at the three time points. An elevated EPDS score of 10 or higher was claimed by 20.8, 12.5, and 18.2% of women, respectively. Higher PSQI scores were positively associated with higher EPDS scores overall ( r = 0.71, p < 0.001) and at each of the individual time points ( r = 0.79, p < 0.0001; r = 0.52, p = 0.04; and r = 0.70, p = 0.016, respectively). None of the women reporting good sleep quality had elevated EPDS scores. Conclusion Poor sleep is commonly reported around delivery, and at 1 and 2 months postpartum, and there is an association between poor sleep and depression symptoms.

Repetitive transcranial magnetic stimulation as a treatment for Alzheimer's disease: A randomized placebo-controlled double-blind clinical trial.

We report results of a large multisite double-blind randomized trial investigating the short and long-term efficacy of repetitive transcranial magnetic stimulation (rTMS) applied to patients with Alzheimer's disease (AD) at mild to moderate stages, in doses of either 2 or 4 weeks of treatment (5 days/week), whilst compared with 4 weeks of sham rTMS. Randomization to treatment group was stratified based on age and severity. The objectives of this study were to: 1) investigate the efficacy of active rTMS versus sham, 2) investigate the effect of dose of treatment (2 or 4 weeks), and 3) investigate the length of benefits from treatment. The rTMS pulses (20 â€‹Hz, 30 pulses/train, 25 trains, 10-s intertrain interval) were applied serially to the left and right dorsolateral prefrontal cortex using neuro-navigation. We compared the primary outcome measure's (ADAS-Cog) score changes from pre- to post-treatment, with assessments at baseline and 4 more times up to 6 months post-treatment. Data of 135 patients were analyzed. The mean total ADAS-Cog score at baseline did not differ between the active and sham treatment groups, nor across the three study sites. The overall results show significant cognitive improvement after treatment up to two months post-treatment with either sham or active coils. The results show both short and long-term benefits of active rTMS treatment but also show similar benefits for sham coil treatment of mild/moderate AD. We discuss this finding in the context of the existing literature on rTMS therapy for AD, as well as evidence of the sham coil's potential to induce a low-level current in the brain. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02908815.

Program ACTIVE II: 6- and 12-month outcomes of a treatment approach for major depressive disorder in adults with type 2 diabetes.

AIMS: To evaluate the long-term effects of behavioral treatments on glycemic and psychological outcomes for patients with major depressive disorder (MDD) and type 2 diabetes (T2D). METHODS: Program ACTIVE II was a multicenter randomized controlled comparative effectiveness trial of cognitive behavioral therapy (CBT), exercise (EXER), combination treatment (CBT + EXER) and usual care (UC) for adults with MDD and T2D. RESULTS: Primary outcomes: change in A1c and depressive symptoms at 6- (N = 87) and 12-months (N = 75) from baseline. In those with a baseline A1c ≥7.0 %, CBT + EXER showed lasting A1c benefit at 6- (-1.2 %; SE: 0.6; p = 0.032) and 12-months (-1.4 %; SE: 0.6; p = 0.025) compared to UC. All groups had clinically significant improvements in depressive symptoms. At 6 months, CBT + EXER had significant improvements in diabetes-related distress regimen burden (p = 0.005); and social support (CIRS, p = 0.043) compared to UC. CONCLUSIONS: The Program ACTIVE II CBT + EXER intervention demonstrated a sustained improvement in A1c for a subgroup of study participants with a baseline A1c ≥7.0 %. However, this finding should be considered preliminary because of small sample size. All 3 behavioral intervention groups demonstrated improvements in psychosocial outcomes one-year post-intervention. These findings point to the enduring benefits of community-based interventions to extend the availability of depression treatment for T2D patients.

Can Brain Volume-Driven Characteristic Features Predict the Response of Alzheimer's Patients to Repetitive Transcranial Magnetic Stimulation? A Pilot Study.

This study is a post-hoc examination of baseline MRI data from a clinical trial investigating the efficacy of repetitive transcranial magnetic stimulation (rTMS) as a treatment for patients with mild-moderate Alzheimer's disease (AD). Herein, we investigated whether the analysis of baseline MRI data could predict the response of patients to rTMS treatment. Whole-brain T1-weighted MRI scans of 75 participants collected at baseline were analyzed. The analyses were run on the gray matter (GM) and white matter (WM) of the left and right dorsolateral prefrontal cortex (DLPFC), as that was the rTMS application site. The primary outcome measure was the Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog). The response to treatment was determined based on ADAS-Cog scores and secondary outcome measures. The analysis of covariance showed that responders to active treatment had a significantly lower baseline GM volume in the right DLPFC and a higher GM asymmetry index in the DLPFC region compared to those in non-responders. Logistic regression with a repeated five-fold cross-validated analysis using the MRI-driven features of the initial 75 participants provided a mean accuracy of 0.69 and an area under the receiver operating characteristic curve of 0.74 for separating responders and non-responders. The results suggest that GM volume or asymmetry in the target area of active rTMS treatment (DLPFC region in this study) may be a weak predictor of rTMS treatment efficacy. These results need more data to draw more robust conclusions.

Tuning the solution phase photophysics of two de novo designed hydrogen bond sensitive 9-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-one derivatives.

Two new fluorophores, 6,7-dimethoxy-9-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-one (DMTCO) and 5-methyl-8,9-dihydro-5H-[1,3]dioxolo[4,5-b]carbazol-6(7H)-one (MDDCO), first of their kind, have been synthesized from the corresponding methoxy and methylenedioxy derivatives of 2,3,4,9-tetrahydro-1H-carbazol-1-one respectively. Comprehensive photophysical characterization of these compounds has been carried out in sixteen different homogeneous solvents and binary solvent mixtures. Both of these compounds are sensitive to solvent polarity, but the sensitivity is much higher in electronic excited state observed by steady-state and time-resolved fluorescence experiments than in ground state studied by UV-vis absorption spectroscopy. The fluorescence spectral shifts are linearly correlated with the empirical parameters of the protic solvents and also the quantitative influence of the empirical solvent parameters on the emission maxima of the compounds has been calculated. The change in dipole moment of the compounds in their excited state has been calculated from the shifts in corresponding emission maxima in pure solvents. A higher dipole moment change of both DMTCO and MDDCO in protic solvents is due to intermolecular hydrogen bonding which is further confirmed by the comparison of their behaviour in toluene-acetonitrile and toluene-methanol solvent mixtures. From structural features, MDDCO is more planar compared to DMTCO, which is reflected better in fluorescence quenching of the former with organic bases, N,N-dimethylaniline and N,N-diethylaniline. Laser flash photolysis experiments prove that the quenching interaction originates from photoinduced electron transfer from the bases to the compounds.