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A multifunctional microRNA, miR-155, has been recently recognized as an important modulator of numerous biological processes. In our previous in vitro studies, miR-155 was identified as a potential regulator of the endothelial morphogenesis. The present study demonstrates that in vivo inhibition of miR-155 supports cerebral vasculature after experimental stroke. Intravenous injections of a specific miR-155 inhibitor were initiated at 48 h after mouse distal middle cerebral artery occlusion (dMCAO). Microvasculature in peri-infarct area, infarct size, and animal functional recovery were assessed at 1, 2, and 3 weeks after dMCAO. Using in vivo two-photon microscopy, we detected improved blood flow and microvascular integrity in the peri-infarct area of miR-155 inhibitor-injected mice. Electron microscopy revealed that, in contrast to the control group, these animals demonstrated well preserved capillary tight junctions (TJs). Western blot analysis data indicate that improved TJ integrity in the inhibitor-injected animals could be associated with stabilization of the TJ protein ZO-1 and mediated by the miR-155 target protein Rheb. MRI analysis showed significant (34%) reduction of infarct size in miR-155 inhibitor-injected animals at 21 d after dMCAO. Reduced brain injury was confirmed by electron microscopy demonstrating decreased neuronal damage in the peri-infarct area of stroke. Preservation of brain tissue was reflected in efficient functional recovery of inhibitor-injected animals. Based on our findings, we propose that in vivo miR-155 inhibition after ischemia supports brain microvasculature, reduces brain tissue damage, and improves the animal functional recovery. [ABSTRACT FROM AUTHOR]

There is an increased demand for Chinese medicinal plants in the U.S., with little known about the feasibility of production of these species outside of China. The purpose of this study was to develop basic agronomic data for selected Chinese medicinal plant species.Agastache rugosa, Schizonepeta tenuifolia, Leonurus japonicus, andLeonurus sibiricuswere grown in a randomized complete block design with 0, 100, or 200 kg.ha−1of nitrogen (N). At 100 kg.ha−1of N, a significant increase in yield of all species was observed as compared to the 0 kg.ha−1control. Average dry yield per plant at 100 kg.ha−1of N was 44.7 g for A. rugosa herb, 52.6 g forS. tenuifoliainflorescences, 42.7 g forL. japonicusbasal rosette, and 46.9 g forL. sibiricusbasal rosette. Yields ofA. rugosaand bothLeonurusspecies increased significantly again at 200 kg.ha−1of N as compared to 100 kg.ha−1, while the increase in yield between these two levels was slight forS. tenuifolia. Results from these trials indicate that all four of the selected species are suitable for cultivation in the northeastern U.S. [ABSTRACT FROM PUBLISHER]

We present field observations of carbon isotope discrimination (Δ) and internal conductance of CO2 ( gi) collected using tunable diode laser spectroscopy (TDL). Δ ranged from 12.0 to 27.4‰ over diurnal periods with daily means from 16.3 ± 0.2‰ during drought to 19.0 ± 0.5‰ during monsoon conditions. We observed a large range in gi, with most estimates between 0.04 and 4.0 µmol m−2 s−1 Pa−1. We tested the comprehensive Farquhar, O'Leary and Berry model of Δ (Δcomp), a simplified form of Δcomp (Δsimple) and a recently suggested amendment (Δrevised). Sensitivity analyses demonstrated that varying gi had a substantial effect on Δcomp, resulting in mean differences between observed Δ (Δobs) and Δcomp ranging from 0.04 to 9.6‰. First-order regressions adequately described the relationship between Δ and the ratio of substomatal to atmospheric CO2 partial pressure ( pi/ pa) on all 3 d, but second-order models better described the relationship in July and August. The three tested models each best predicted Δobs on different days. In June, Δsimple outperformed Δcomp and Δrevised, but incorporating gi and all non-photosynthetic fractionations improved model predictions in July and August. [ABSTRACT FROM AUTHOR]

• dMRS is a noninvasive, cost-effective sequence for assessing microglial activation. • The sequence has detected neuroinflammation in LPS challenges and serious diseases. • It is unclear if dMRS can detect subtle neuroinflammation without LPS injections. • Here, dMRS reflected intrinsic LPS via neurometabolite diffusivity properties. • The sequence is sensitive to intrinsic plasma levels of LPS without LPS injections. Neuroinflammation is a key component underlying multiple neurological disorders, yet non-invasive and cost-effective assessment of in vivo neuroinflammatory processes in the central nervous system remains challenging. Diffusion weighted magnetic resonance spectroscopy (dMRS) has shown promise in addressing these challenges by measuring diffusivity properties of different neurometabolites, which can reflect cell-specific morphologies. Prior work has demonstrated dMRS utility in capturing microglial reactivity in the context of lipopolysaccharide (LPS) challenges and serious neurological disorders, detected as changes of microglial metabolite diffusivity properties. However, the extent to which such dMRS metrics are capable of detecting subtler and more nuanced levels of neuroinflammation in populations without overt neuropathology is unknown. Here we examined the relationship between intrinsic, gut-derived levels of systemic LPS and dMRS-based apparent diffusion coefficients (ADC) of choline, creatine, and N-acetylaspartate (NAA) in two brain regions: the thalamus and the corona radiata. Higher plasma LPS concentrations were significantly associated with increased ADC of choline and NAA in the thalamic region, with no such relationships observed in the corona radiata for any of the metabolites examined. As such, dMRS may have the sensitivity to measure microglial reactivity across populations with highly variable levels of neuroinflammation, and holds promising potential for widespread applications in both research and clinical settings. [ABSTRACT FROM AUTHOR]

Background Sharing needles and ancillary injecting equipment is a primary risk exposure for hepatitis C virus (HCV) infection among people who inject drugs (PWID); however, infectivity of these exposures is not well quantified. We aimed to estimate per-event HCV infectivity associated with receptive needle sharing (RNS) among susceptible PWID. Methods Participants in a prospective cohort study of young adult PWID who were anti-HCV and HCV RNA negative at baseline and attended at least 2 follow-up study visits between 2003 and 2014 were eligible. Data were selected from the first HCV-negative through the first HCV-positive visit (or last HCV-negative among those uninfected). Anti-HCV and HCV-RNA tests were used to determine infection status. A probabilistic exposure model linking observed HCV infection outcomes to self-reported exposure events was applied to estimate infectivity. Results Among 344 participants, a maximum likelihood estimate considering RNS yielded a pooled population per RNS event HCV probability of 0.25% (95% confidence interval [CI], 0.10%–0.43%), and 1.12% (95% CI, 0.48%–2.35%) among those who acquired any HCV infection (primary or reinfection). Conclusions HCV is highly infectious in association with RNS, a primary injection-related risk exposure. Our infectivity estimate among participants who acquired any HCV infection is 1.7 times higher than that estimated for HIV infection in PWID and 2.24 times higher than that estimated among health care workers exposed through needle sticks. The strengths of this study include the assessment of receptive needle sharing events, the prospective design, and relatively short recall and testing periods. These results can inform transmission models and research to prevent HCV infection. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Clinical Outcomes of Rural Patients with Diabetes Treated by ECHO-Trained Providers Versus an Academic Medical Center." The correction provides the correct DOI for the article and states that it has been republished with open access. The corresponding author's contact information is also provided. The publisher, Springer Nature, remains neutral regarding jurisdictional claims and institutional affiliations. The original article can be found online. [Extracted from the article]

Cerebrovascular dysfunction following mild traumatic brain injury (mTBI) is understudied relative to other microstructural injuries, especially during neurodevelopment. The blood-oxygen level dependent response was used to investigate cerebrovascular reactivity (CVR) in response to hypercapnia following pediatric mTBI (pmTBI; ages 8–18 years), as well as pseudocontinuous arterial spin labeling to measure cerebral blood flow (CBF). Data were collected ∼1-week (N = 107) and 4 months (N = 73) post-injury. Sex- and age-matched healthy controls (HC) underwent identical examinations at comparable time points (N = 110 and N = 91). Subtle clinical and cognitive deficits existed at ∼1 week that resolved for some, but not all domains at 4 months post-injury. At both visits, pmTBI showed an increased maximal fit between end-tidal CO2 regressor and the cerebrovascular response across multiple regions (primarily fronto-temporal), as well as increased latency to maximal fit in independent regions (primarily posterior). Hypoperfusion was also noted within the bilateral cerebellum. A biphasic relationship existed between CVR amplitude and age (i.e., positive until 14.5 years, negative thereafter) in both gray and white matter, but these neurodevelopment effects did not moderate injury effects. CVR metrics were not associated with post-concussive symptoms or cognitive deficits. In conclusion, cerebrovascular dysfunction may persist for up to four months following pmTBI. [ABSTRACT FROM AUTHOR]

Background: Despite clinical practice guidelines prioritizing cardiorenal risk reduction, national trends in diabetes outcomes, particularly in rural communities, do not mirror the benefits seen in clinical trials with emerging therapeutics and technologies.Project ECHO supports implementation of guidelines in under-resourced areas through virtual communities of practice, sharing of best practices, and case-based learning. We hypothesized that diabetes outcomes of patients treated by ECHO-trained primary care providers (PCPs) would be similar to those of patients treated by specialists at an academic medical center.Specialists from the University of New Mexico (UNM) launched a weekly diabetes ECHO program to mentor dyads consisting of a PCP and community health worker at ten rural clinics.We compared cardiorenal risk factor changes in patients with diabetes treated by ECHO-trained dyads to patients treated by specialists at the UNM Diabetes Comprehensive Care Center (DCCC). Eligible participants included adults with type 1 diabetes, type 2 diabetes on insulin, or diabetes of either type with A1c > 9%.The primary outcome was change from baseline in A1c in the ECHO and DCCC cohorts. Secondary outcomes included changes in body mass index (BMI), blood pressure, cholesterol, and urine albumin to creatinine ratio (UACR).Compared to the DCCC cohort (n = 151), patients in the ECHO cohort (n = 856) experienced greater A1c reduction (−1.2% vs −0.6%; p = 0.02 for difference in difference). BMI decreased in the Endo ECHO cohort and increased in the DCCC cohort (−0.2 vs. +1.3 kg/m2; p = 0.003 for difference in difference). Diastolic blood pressure declined in the Endo ECHO cohort only. Improvements of similar magnitude were observed in low-density lipoprotein cholesterol in both groups. UACR remained stable in both groups.ECHO may be a suitable intervention for improving diabetes outcomes in rural, under-resourced communities with limited access to a specialist.Objective: Despite clinical practice guidelines prioritizing cardiorenal risk reduction, national trends in diabetes outcomes, particularly in rural communities, do not mirror the benefits seen in clinical trials with emerging therapeutics and technologies.Project ECHO supports implementation of guidelines in under-resourced areas through virtual communities of practice, sharing of best practices, and case-based learning. We hypothesized that diabetes outcomes of patients treated by ECHO-trained primary care providers (PCPs) would be similar to those of patients treated by specialists at an academic medical center.Specialists from the University of New Mexico (UNM) launched a weekly diabetes ECHO program to mentor dyads consisting of a PCP and community health worker at ten rural clinics.We compared cardiorenal risk factor changes in patients with diabetes treated by ECHO-trained dyads to patients treated by specialists at the UNM Diabetes Comprehensive Care Center (DCCC). Eligible participants included adults with type 1 diabetes, type 2 diabetes on insulin, or diabetes of either type with A1c > 9%.The primary outcome was change from baseline in A1c in the ECHO and DCCC cohorts. Secondary outcomes included changes in body mass index (BMI), blood pressure, cholesterol, and urine albumin to creatinine ratio (UACR).Compared to the DCCC cohort (n = 151), patients in the ECHO cohort (n = 856) experienced greater A1c reduction (−1.2% vs −0.6%; p = 0.02 for difference in difference). BMI decreased in the Endo ECHO cohort and increased in the DCCC cohort (−0.2 vs. +1.3 kg/m2; p = 0.003 for difference in difference). Diastolic blood pressure declined in the Endo ECHO cohort only. Improvements of similar magnitude were observed in low-density lipoprotein cholesterol in both groups. UACR remained stable in both groups.ECHO may be a suitable intervention for improving diabetes outcomes in rural, under-resourced communities with limited access to a specialist.Design: Despite clinical practice guidelines prioritizing cardiorenal risk reduction, national trends in diabetes outcomes, particularly in rural communities, do not mirror the benefits seen in clinical trials with emerging therapeutics and technologies.Project ECHO supports implementation of guidelines in under-resourced areas through virtual communities of practice, sharing of best practices, and case-based learning. We hypothesized that diabetes outcomes of patients treated by ECHO-trained primary care providers (PCPs) would be similar to those of patients treated by specialists at an academic medical center.Specialists from the University of New Mexico (UNM) launched a weekly diabetes ECHO program to mentor dyads consisting of a PCP and community health worker at ten rural clinics.We compared cardiorenal risk factor changes in patients with diabetes treated by ECHO-trained dyads to patients treated by specialists at the UNM Diabetes Comprehensive Care Center (DCCC). Eligible participants included adults with type 1 diabetes, type 2 diabetes on insulin, or diabetes of either type with A1c > 9%.The primary outcome was change from baseline in A1c in the ECHO and DCCC cohorts. Secondary outcomes included changes in body mass index (BMI), blood pressure, cholesterol, and urine albumin to creatinine ratio (UACR).Compared to the DCCC cohort (n = 151), patients in the ECHO cohort (n = 856) experienced greater A1c reduction (−1.2% vs −0.6%; p = 0.02 for difference in difference). BMI decreased in the Endo ECHO cohort and increased in the DCCC cohort (−0.2 vs. +1.3 kg/m2; p = 0.003 for difference in difference). Diastolic blood pressure declined in the Endo ECHO cohort only. Improvements of similar magnitude were observed in low-density lipoprotein cholesterol in both groups. UACR remained stable in both groups.ECHO may be a suitable intervention for improving diabetes outcomes in rural, under-resourced communities with limited access to a specialist.Participants: Despite clinical practice guidelines prioritizing cardiorenal risk reduction, national trends in diabetes outcomes, particularly in rural communities, do not mirror the benefits seen in clinical trials with emerging therapeutics and technologies.Project ECHO supports implementation of guidelines in under-resourced areas through virtual communities of practice, sharing of best practices, and case-based learning. We hypothesized that diabetes outcomes of patients treated by ECHO-trained primary care providers (PCPs) would be similar to those of patients treated by specialists at an academic medical center.Specialists from the University of New Mexico (UNM) launched a weekly diabetes ECHO program to mentor dyads consisting of a PCP and community health worker at ten rural clinics.We compared cardiorenal risk factor changes in patients with diabetes treated by ECHO-trained dyads to patients treated by specialists at the UNM Diabetes Comprehensive Care Center (DCCC). Eligible participants included adults with type 1 diabetes, type 2 diabetes on insulin, or diabetes of either type with A1c > 9%.The primary outcome was change from baseline in A1c in the ECHO and DCCC cohorts. Secondary outcomes included changes in body mass index (BMI), blood pressure, cholesterol, and urine albumin to creatinine ratio (UACR).Compared to the DCCC cohort (n = 151), patients in the ECHO cohort (n = 856) experienced greater A1c reduction (−1.2% vs −0.6%; p = 0.02 for difference in difference). BMI decreased in the Endo ECHO cohort and increased in the DCCC cohort (−0.2 vs. +1.3 kg/m2; p = 0.003 for difference in difference). Diastolic blood pressure declined in the Endo ECHO cohort only. Improvements of similar magnitude were observed in low-density lipoprotein cholesterol in both groups. UACR remained stable in both groups.ECHO may be a suitable intervention for improving diabetes outcomes in rural, under-resourced communities with limited access to a specialist.Main Measures: Despite clinical practice guidelines prioritizing cardiorenal risk reduction, national trends in diabetes outcomes, particularly in rural communities, do not mirror the benefits seen in clinical trials with emerging therapeutics and technologies.Project ECHO supports implementation of guidelines in under-resourced areas through virtual communities of practice, sharing of best practices, and case-based learning. We hypothesized that diabetes outcomes of patients treated by ECHO-trained primary care providers (PCPs) would be similar to those of patients treated by specialists at an academic medical center.Specialists from the University of New Mexico (UNM) launched a weekly diabetes ECHO program to mentor dyads consisting of a PCP and community health worker at ten rural clinics.We compared cardiorenal risk factor changes in patients with diabetes treated by ECHO-trained dyads to patients treated by specialists at the UNM Diabetes Comprehensive Care Center (DCCC). Eligible participants included adults with type 1 diabetes, type 2 diabetes on insulin, or diabetes of either type with A1c > 9%.The primary outcome was change from baseline in A1c in the ECHO and DCCC cohorts. Secondary outcomes included changes in body mass index (BMI), blood pressure, cholesterol, and urine albumin to creatinine ratio (UACR).Compared to the DCCC cohort (n = 151), patients in the ECHO cohort (n = 856) experienced greater A1c reduction (−1.2% vs −0.6%; p = 0.02 for difference in difference). BMI decreased in the Endo ECHO cohort and increased in the DCCC cohort (−0.2 vs. +1.3 kg/m2; p = 0.003 for difference in difference). Diastolic blood pressure declined in the Endo ECHO cohort only. Improvements of similar magnitude were observed in low-density lipoprotein cholesterol in both groups. UACR remained stable in both groups.ECHO may be a suitable intervention for improving diabetes outcomes in rural, under-resourced communities with limited access to a specialist.Key Results: Despite clinical practice guidelines prioritizing cardiorenal risk reduction, national trends in diabetes outcomes, particularly in rural communities, do not mirror the benefits seen in clinical trials with emerging therapeutics and technologies.Project ECHO supports implementation of guidelines in under-resourced areas through virtual communities of practice, sharing of best practices, and case-based learning. We hypothesized that diabetes outcomes of patients treated by ECHO-trained primary care providers (PCPs) would be similar to those of patients treated by specialists at an academic medical center.Specialists from the University of New Mexico (UNM) launched a weekly diabetes ECHO program to mentor dyads consisting of a PCP and community health worker at ten rural clinics.We compared cardiorenal risk factor changes in patients with diabetes treated by ECHO-trained dyads to patients treated by specialists at the UNM Diabetes Comprehensive Care Center (DCCC). Eligible participants included adults with type 1 diabetes, type 2 diabetes on insulin, or diabetes of either type with A1c > 9%.The primary outcome was change from baseline in A1c in the ECHO and DCCC cohorts. Secondary outcomes included changes in body mass index (BMI), blood pressure, cholesterol, and urine albumin to creatinine ratio (UACR).Compared to the DCCC cohort (n = 151), patients in the ECHO cohort (n = 856) experienced greater A1c reduction (−1.2% vs −0.6%; p = 0.02 for difference in difference). BMI decreased in the Endo ECHO cohort and increased in the DCCC cohort (−0.2 vs. +1.3 kg/m2; p = 0.003 for difference in difference). Diastolic blood pressure declined in the Endo ECHO cohort only. Improvements of similar magnitude were observed in low-density lipoprotein cholesterol in both groups. UACR remained stable in both groups.ECHO may be a suitable intervention for improving diabetes outcomes in rural, under-resourced communities with limited access to a specialist.Conclusions: Despite clinical practice guidelines prioritizing cardiorenal risk reduction, national trends in diabetes outcomes, particularly in rural communities, do not mirror the benefits seen in clinical trials with emerging therapeutics and technologies.Project ECHO supports implementation of guidelines in under-resourced areas through virtual communities of practice, sharing of best practices, and case-based learning. We hypothesized that diabetes outcomes of patients treated by ECHO-trained primary care providers (PCPs) would be similar to those of patients treated by specialists at an academic medical center.Specialists from the University of New Mexico (UNM) launched a weekly diabetes ECHO program to mentor dyads consisting of a PCP and community health worker at ten rural clinics.We compared cardiorenal risk factor changes in patients with diabetes treated by ECHO-trained dyads to patients treated by specialists at the UNM Diabetes Comprehensive Care Center (DCCC). Eligible participants included adults with type 1 diabetes, type 2 diabetes on insulin, or diabetes of either type with A1c > 9%.The primary outcome was change from baseline in A1c in the ECHO and DCCC cohorts. Secondary outcomes included changes in body mass index (BMI), blood pressure, cholesterol, and urine albumin to creatinine ratio (UACR).Compared to the DCCC cohort (n = 151), patients in the ECHO cohort (n = 856) experienced greater A1c reduction (−1.2% vs −0.6%; p = 0.02 for difference in difference). BMI decreased in the Endo ECHO cohort and increased in the DCCC cohort (−0.2 vs. +1.3 kg/m2; p = 0.003 for difference in difference). Diastolic blood pressure declined in the Endo ECHO cohort only. Improvements of similar magnitude were observed in low-density lipoprotein cholesterol in both groups. UACR remained stable in both groups.ECHO may be a suitable intervention for improving diabetes outcomes in rural, under-resourced communities with limited access to a specialist. [ABSTRACT FROM AUTHOR]

The brain is highly dynamic, reorganizing its activity at different interacting spatial and temporal scales, including variation within and between brain networks. The chronnectome is a model of the brain in which nodal activity and connectivity patterns change in fundamental and recurring ways over time. Most literature assumes fixed spatial nodes/networks, ignoring the possibility that spatial nodes/networks may vary in time. Here, we introduce an approach to calculate a spatially fluid chronnectome (called the spatial chronnectome for clarity), which focuses on the variations of networks coupling at the voxel level, and identify a novel set of spatially dynamic features. Results reveal transient spatially fluid interactions between intra‐ and internetwork relationships in which brain networks transiently merge and separate, emphasizing dynamic segregation and integration. Brain networks also exhibit distinct spatial patterns with unique temporal characteristics, potentially explaining a broad spectrum of inconsistencies in previous studies that assumed static networks. Moreover, we show anticorrelative connections to brain networks are transient as opposed to constant across the entire scan. Preliminary assessments using a multi‐site dataset reveal the ability of the approach to obtain new information and nuanced alterations that remain undetected during static analysis. Patients with schizophrenia (SZ) display transient decreases in voxel‐wise network coupling within visual and auditory networks, and higher intradomain coupling variability. In summary, the spatial chronnectome represents a new direction of research enabling the study of functional networks which are transient at the voxel level, and the identification of mechanisms for within‐ and between‐subject spatial variability. [ABSTRACT FROM AUTHOR]

Abstract: Many animals undergo extended periods of fasting. During these fasts, animals oxidize a ratio of macronutrients dependent on the nutritional, energetic, and hydric requirements of the fasting period. In this study, we use Japanese quail (Coturnix coturnix japonica), a bird with natural intermediate fasting periods, to examine macronutrient use during a 6d fast. We raised groups of quail on isotopically labeled materials (13C-1-leucine, 13C-U-glucose, or 13C-1-palmitic acid) with the intent of labeling specific macronutrient/tissue pools in each treatment, and then traced their use as fuels by measuring the δ13C values of breath CO2. Based on changes in δ13C values during the fast, it appears that the carbohydrate label,13C-U-glucose, was largely incorporated into the lipid pool and thus breath samples ultimately reflected lipid use rather than carbohydrate use. In the lipid treatment, the 13C-1-palmitic acid faithfully labeled the lipid pool and was reflected in the kinetics δ13C values in breath CO2 during the fast. Endogenous lipid oxidation peaked after 24h of fasting and remained constantly elevated thereafter. The protein label,13C-1-leucine, showed clear diurnal periods of protein sparing and degradation, with maximal rates of protein oxidation occurring at night and the lowest rates occurring during the day time. This stable isotope tracer method provides a noninvasive approach to study the nutrient dynamics of fasting animals and should provide new insights into how different types of animals use specific nutrient pools during fasting and possibly other non-steady physiological states. [Copyright &y& Elsevier]

The Global ECT MRI Research Collaboration (GEMRIC) has collected clinical and neuroimaging data of patients treated with electroconvulsive therapy (ECT) from around the world. Results to date have focused on neuroimaging correlates of antidepressant response. GEMRIC sites have also collected longitudinal cognitive data. Here, we summarize the existing GEMRIC cognitive data and provide recommendations for prospective data collection for future ECT-imaging investigations. We describe the criteria for selection of cognitive measures for mega-analyses: Trail Making Test Parts A (TMT-A) and B (TMT-B), verbal fluency category (VFC), verbal fluency letter (VFL), and percent retention from verbal learning and memory tests. We performed longitudinal data analysis focused on the pre-/post-ECT assessments with healthy comparison (HC) subjects at similar timepoints and assessed associations between demographic and ECT parameters with cognitive changes. The study found an interaction between electrode placement and treatment number for VFC (F(1,107) = 4.14, p = 0.04). Higher treatment was associated with decreased VFC performance with right unilateral electrode placement. Percent retention showed a main effect for group, with post-hoc analysis indicating decreased cognitive performance among the HC group. However, there were no significant effects of group or group interactions observed for TMT-A, TMT-B, or VFL. We assessed the current GEMRIC cognitive data and acknowledge the limitations associated with this data set including the limited number of neuropsychological domains assessed. Aside from the VFC and treatment number relationship, we did not observe ECT-mediated neurocognitive effects in this investigation. We provide prospective cognitive recommendations for future ECT-imaging investigations focused on strong psychometrics and minimal burden to subjects., Competing Interests: Declaration of competing interest HBM part in educational events sponsored by Livanova and Rovi. RH has received consulting and speaker fees from Boehringer Ingelheim International GmbH, Janssen-Cilag GmbH and ROVI GmbH in the last three years. All other authors report no biomedical financial interests or potential conflicts of interest with this work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Electroconvulsive therapy (ECT) pulse amplitude, which dictates the induced electric field (E-field) magnitude in the brain, is presently fixed at 800 or 900 milliamperes (mA) without clinical or scientific rationale. We have previously demonstrated that increased E-field strength improves ECT's antidepressant effect but worsens cognitive outcomes. Amplitude-determined seizure titration may reduce the E-field variability relative to fixed amplitude ECT. In this investigation, we assessed the relationships among amplitude-determined seizure-threshold (ST a ), E-field magnitude, and clinical outcomes in older adults (age range 50 to 80 years) with depression. Subjects received brain imaging, depression assessment, and neuropsychological assessment pre-, mid-, and post-ECT. ST a was determined during the first treatment with a Soterix Medical 4×1 High Definition ECT Multi-channel Stimulation Interface (Investigation Device Exemption: G200123). Subsequent treatments were completed with right unilateral electrode placement (RUL) and 800 mA. We calculated E brain defined as the 90th percentile of E-field magnitude in the whole brain for RUL electrode placement. Twenty-nine subjects were included in the final analyses. E brain per unit electrode current, E brain /I, was associated with ST a . ST a was associated with antidepressant outcomes at the mid-ECT assessment and bitemporal electrode placement switch. E brain /I was associated with changes in category fluency with a large effect size. The relationship between ST a and E brain /I extends work from preclinical models and provides a validation step for ECT E-field modeling. ECT with individualized amplitude based on E-field modeling or ST a has the potential to enhance neuroscience-based ECT parameter selection and improve clinical outcomes., (© 2024. The Author(s).)

Background: Electroconvulsive therapy (ECT) is efficacious for treatment-resistant depression. Treatment-induced cognitive impairment can adversely impact functional outcomes. Our pilot study linked the electric field to ictal theta power from a single suprathreshold treatment and linked ictal theta power to changes in phonemic fluency. In this study, we set out to replicate our findings and expand upon the utility of ictal theta power as a potential cognitive biomarker., Methods: Twenty-seven participants (18 female and 9 male) received right unilateral ECT for treatment-resistant depression. Pre-ECT magnetic resonance imaging and finite element modeling determined the 90th percentile maximum electric field in the brain. Two-lead electroencephalographs were digitally captured across the ECT course, with the earliest suprathreshold treatment used to determine power spectral density. Clinical and cognitive outcomes were assessed pre-, mid-, and post-ECT. We assessed the relationship between the electric field in the brain, ictal theta power, clinical outcome (Inventory of Depressive Symptomatology), and cognitive outcomes (phonemic and semantic fluency) with linear models., Results: Ictal theta power in the Fp1 and Fp2 channels was associated with the electric field, antidepressant outcome, and phonemic and semantic fluency. The relationship between ictal theta power and phonemic fluency was strengthened in the longitudinal analysis. The electric field in the brain was directly associated with phonemic and semantic fluency but not with antidepressant outcome., Conclusions: Ictal theta power is a potential cognitive biomarker early on in the ECT course to help guide parameter changes. Larger studies are needed to further assess ictal theta power's role in predicting mood outcome and changes with ECT parameters., (Copyright © 2023 Society of Biological Psychiatry. All rights reserved.)

Objective: Hippocampal atrophy is an indicator of emerging dementia in PD, though it is unclear whether cerebral spinal fluid (CSF) Abeta-42, t-tau, or alpha-syn predict hippocampal subfield atrophy in a de novo cohort of PD patients. To examine whether levels of CSF alpha-synuclein (alpha-syn), beta-amyloid 1-42 (Abeta-42) , or total-tau (t-tau) are associated with hippocampal subfield volumes over time., Methods: We identified a subset of Parkinson's Progression Markers Initiative (PPMI) de novo PD patients with longitudinal T1-weighted imaging (baseline plus at least two additional visits across 12, 24, and 48 months) and CSF biomarkers available at baseline. We performed cross-sectional, regression, and linear mixed model analyses to evaluate the baseline and longitudinal CSF biomarkers, hippocampal subfields, and cognition. A false discovery rate (FDR) was used to correct for multiple comparisons., Results: 88 PD-CN and 21 PD-MCI had high quality longitudinal data. PD-MCI patients exhibited reduced bilateral CA1 volumes relative to PD-CN, though there were no significant differences in CSF biomarkers between these groups. Relationships between CSF biomarkers and hippocampal subfields changed over time, with a general pattern that lower CSF Abeta-42, higher t-tau and higher alpha-syn were associated with smaller hippocampal subfields, primarily in the right hemisphere., Conclusion: We replicated prior reports that demonstrated reduced CA1 volumes in PD-MCI in a de novo PD cohort. CSF biomarkers were associated with individual subfields, with evidence that the increased CSF t-tau was associated with smaller subiculum volumes at baseline and over time, though there was no clear indication that the subfields associated with cognition (CA1 and HATA) were associated with CSF biomarkers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Depression and diabetes are co-occurring epidemics. This article explores the association between depression and diabetes in a cohort of Latinx patients with diabetes from low-income households. Data were gathered in Albuquerque, New Mexico (U.S.) between 2016 and 2020 as part of a patient-engaged comparative effectiveness trial comparing two culturally appropriate diabetes self-management programs-the Chronic Care Model (CCM) and the standard of care, Diabetes Self-Management Support Empowerment Model (DSMS). We proposed that the program most culturally and contextually situated in the life of the patient would have the greatest impact on diabetes self-management. Participants were enrolled as dyads-226 Latinx diabetes patient participants (PPs) from low-income households and 226 social support participants (SSPs). Data gathered at baseline, 3, 6, and 12 months included a measure of depression and A1c testing. Outcomes between programs were analyzed using longitudinal linear mixed modeling, adjusted for patient demographic characteristics and other potential confounding covariates. Patient A1c had an initial slight decrease at 3 months in both programs. At CCM, patients with a very high A1c (greater than 10%) demonstrated a clinically meaningful decrease in A1c over time. Patients at CCM experienced a large initial decrease in depression and continued to decrease throughout the study, while patients at DSMS showed a slight initial decrease through 6 months, but depression increased again by 12 months, nearly rebounding to baseline levels. A subgroup analysis revealed that a higher baseline A1c was associated with higher depression, and patients with higher A1c achieved greater reductions in depression at CCM than at DSMS. CCM scored higher on Consumer Assessment of Healthcare Providers and Systems cultural competence (CAHPS-CC). Interpretation of results suggests that the more culturally, contextually situated program, CCM, had better outcomes. This study demonstrates that culturally and contextually situating a diabetes intervention can deliver improved benefits for Latinx patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Electroconvulsive therapy (ECT) remains the gold-standard treatment for patients with depressive episodes, but the underlying mechanisms for antidepressant response and procedure-induced cognitive side effects have yet to be elucidated. Such mechanisms may be complex and involve certain ECT parameters and brain regions. Regarding parameters, the electrode placement (right unilateral or bitemporal) determines the geometric shape of the electric field (E-field), and amplitude determines the E-field magnitude in select brain regions (e.g., hippocampus). Here, we aim to determine the relationships between hippocampal E-field strength, hippocampal neuroplasticity, and antidepressant and cognitive outcomes. We used hippocampal E-fields and volumes generated from a randomized clinical trial that compared right unilateral electrode placement with different pulse amplitudes (600, 700, and 800 mA). Hippocampal E-field strength was variable but increased with each amplitude arm. We demonstrated a linear relationship between right hippocampal E-field and right hippocampal neuroplasticity. Right hippocampal neuroplasticity mediated right hippocampal E-field and antidepressant outcomes. In contrast, right hippocampal E-field was directly related to cognitive outcomes as measured by phonemic fluency. We used receiver operating characteristic curves to determine that the maximal right hippocampal E-field associated with cognitive safety was 112.5 V/m. Right hippocampal E-field strength was related to the whole-brain ratio of E-field strength per unit of stimulation current, but this whole-brain ratio was unrelated to antidepressant or cognitive outcomes. We discuss the implications of optimal hippocampal E-field dosing to maximize antidepressant outcomes and cognitive safety with individualized amplitudes., (© 2021. The Author(s).)