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Discusses the history of the sperm factor model. Difference between sperm oocyte activating factor and sperm oscillogen; Glucosamine phosphate deaminase; Multiple sperm factors.

Objective: To evaluate racial and ethnic differences in patient experience among VA primary care users at the Veterans Integrated Service Network (VISN) level., Data Source and Study Setting: We performed a secondary analysis of the VA Survey of Healthcare Experiences of Patients-Patient Centered Medical Home for fiscal years 2016-2019., Study Design: We compared 28 patient experience measures (six each in the domains of access and care coordination, 16 in the domain of person-centered care) between minoritized racial and ethnic groups (American Indian or Alaska Native [AIAN], Asian, Black, Hispanic, Multi-Race, Native Hawaiian or Other Pacific Islander [NHOPI]) and White Veterans. We used weighted logistic regression to test differences between minoritized and White Veterans, controlling for age and gender., Data Collection/extraction Methods: We defined meaningful difference as both statistically significant at two-tailed p < 0.05 with a relative difference ≥10% or ≤-10%. Within VISNs, we included tests of group differences with adequate power to detect meaningful relative differences from a minimum of five comparisons (domain agnostic) per VISN, and separately for a minimum of two for access and care coordination and four for person-centered care domains. We report differences as disparities/large disparities (relative difference ≥10%/≥ 25%), advantages (experience worse or better, respectively, than White patients), or equivalence., Principal Findings: Our analytic sample included 1,038,212 Veterans (0.6% AIAN, 1.4% Asian, 16.9% Black, 7.4% Hispanic, 0.8% Multi-Race, 0.8% NHOPI, 67.7% White). Across VISNs, the greatest proportion of comparisons indicated disparities for three of seven eligible VISNs for AIAN, 6/10 for Asian, 3/4 for Multi-Race, and 2/6 for NHOPI Veterans. The plurality of comparisons indicated advantages or equivalence for 17/18 eligible VISNs for Black and 12/14 for Hispanic Veterans. AIAN, Asian, Multi-Race, and NHOPI groups had more comparisons indicating disparities by VISN in the access domain than person-centered care and care coordination., Conclusions: We found meaningful differences in patient experience measures across VISNs for minoritized compared to White groups, especially for groups with lower population representation., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Health Services Research published by Wiley Periodicals LLC on behalf of Health Research and Educational Trust.)

Background: In-home remote foot temperature monitoring (RTM) holds promise as a method to reduce foot ulceration in high-risk patients with diabetes. Few studies have evaluated adherence to this method or evaluated the factors associated with noncompliance., Objective: The aims of this study were to estimate noncompliance in patients who were enrolled in RTM nationwide across Department of Veterans Affairs (VA) and to evaluate characteristics associated with noncompliance., Methods: We conducted an observational study including 1137 patients in the VA who were enrolled in RTM between January 2019 and June 2021, with follow-up through October 2021. Patient information was obtained from the VA's electronic health record and RTM use was obtained from the company. Noncompliance was defined as using the mat <2 days per week for ≥4 of the 12 months of follow-up. Using a multivariable model, we calculated odds ratios (ORs) and 95% CIs for associations between various factors and noncompliance and compared using Akaike information criterion statistics, a measure of model fit., Results: The sample was predominantly male (n=1125, 98.94%) ; 21.1% (n=230) were Black and 75.7% (n=825) were White. Overall, 37.6% (428/1137) of patients were classified as noncompliant. In the multivariable model, an intermediate area deprivation index was statistically significantly and inversely associated with noncompliance (area deprivation index 50-74 vs 1-24; OR 0.56, 95% CI 0.35-0.89); factors significantly and positively associated with noncompliance included recent history of osteomyelitis (OR 1.44, 95% CI 1.06-1.97), Gagne comorbidity index score ≥4 (vs ≤0; OR 1.81, 95% CI 1.15-2.83), telehealth encounters (28+ vs <6; OR 1.70, 95% CI 1.02-2.84), hemoglobin A1c≥10 (vs <5.7; OR 2.67, 95% CI 1.27-5.58), and current smoking (OR 2.06, 95% CI 1.32-3.20). Based on Akaike information criterion differences, the strongest factors associated with noncompliance were behavioral factors (poor glucose control [as measured by hemoglobin A1c] and smoking), and to a lesser extent, factors such as a recent history of osteomyelitis and an elevated Gagne comorbidity index, indicating a high comorbidity burden., Conclusions: To reduce the risk of ulcer recurrence and amputation, proactively providing additional support for self-monitoring to patients with characteristics identified in this study (poor glucose control, current smoking, high comorbidity burden) may be helpful. Furthermore, research is needed to better understand barriers to use, and whether the addition of design features, reminders, or incentives may reduce noncompliance and the risk of foot ulcers., (© Alyson J Littman, Andrew K Timmons, Anna Korpak, Kwun C G Chan, Kenneth T Jones, Suzanne Shirley, Kyle Nordrum, Jeffrey Robbins, Suhail Masadeh, Ernest Moy. Originally published in JMIR Diabetes (https://diabetes.jmir.org).)

Cystic fibrosis related diabetes (CFRD), the main co-morbidity in cystic fibrosis (CF), is associated with higher rates of lung function decline. We hypothesize that airway epithelial barrier function is impaired in CF and is further exacerbated under hyperglycemia, worsening pulmonary outcomes. Using 16HBE cells, we studied the effects of hyperglycemia in airway epithelial barrier function. Results show increased paracellular dye flux in CF cells in response to insulin under hyperglycemia. Gene expression experiments identified claudin-4 (CLDN4) as a key tight junction protein dysregulated in CF cells. CLDN4 protein localization by confocal microscopy showed that CLDN4 was tightly localized at tight junctions in WT cells, which did not change under hyperglycemia. ln contrast, CLDN4 was less well-localized in CF cells at normal glucose and localization was worsened under hyperglycemia. Treatment with highly effective modulator compounds (ETI) reversed this trend, and CFTR rescue was not affected by insulin or hyperglycemia. Bulk RNA sequencing showed differences in transcriptional responses in CF compared to WT cells under normal or high glucose, highlighting promising targets for future investigation. One of these targets is protein tyrosine phosphatase receptor type G (PTPRG), which has been previously found to play a role in defective Akt signaling and insulin resistance., (© 2024. The Author(s).)

Purpose: This study examined the differences by sexual orientation in patient-centered care outcomes (including health care experiences and health-related screening) of veterans utilizing Veterans Health Administration (VHA) primary care. Methods: VHA's adapted version of the Consumer Assessment of Healthcare Providers and Systems was used to compare the health care experience of primary care services among sexual minority (SM) and heterosexual veterans. Health care experience measures were dichotomized to "always" versus "less" and stratified by SM status. Health-related screening measures were dichotomous. Survey data were weighted using provided sample weights. Descriptive statistics were performed on sociodemographic characteristics. Logistic regression coefficients were represented as adjusted odds ratios (aORs). A total of 66,348 veterans were included in the analytic sample, of which 2.9% ( n  = 1,935) identified as SM. Sexual orientation was ascertained by self-report measures by veterans. Results: SM veterans were significantly younger (56.95 years vs. 63.43 years, p  < 0.001), were less likely to report that their provider showed respect for what they had to say (aOR: 0.76; 95% confidence interval [CI]: 0.61-0.95), that they were asked about difficulties taking care of their health (aOR: 0.81; 95% CI: 0.67-0.96), and their provider listened carefully to them (aOR: 0.71; 95% CI: 0.57-0.87) compared to heterosexual veterans. Conclusion: Health care experiences differed between SM and heterosexual veterans who sought VHA primary care, suggesting the need to increase provider trainings, which may improve cultural competency and promote a more welcoming and inclusive environment.

Failing to consider disparities in quality measures, such as by race and ethnicity, may obscure inequities in care, which could exist in facilities with overall high-quality ratings. We examined the relationship between overall quality and racial and ethnic disparities in diabetes care quality by health care facility-level performance on a diabetes-related quality measure within a national dataset of veterans using Veterans Health Administration (VA) ambulatory care between March 1, 2020 and Feburary 28, 2021, and were eligible for diabetes quality assessment. We found racial and ethnic disparities in diabetes care quality existed in top-performing VA medical centers (VAMCs) among American Indian or Alaska Native (AIAN) (predicted probability = 30%), Black (predicted probability = 29%), and Hispanic VA-users (predicted probability = 30%) vs White VA-users (predicted probability = 26%). While disparities among Black and Hispanic VA-users were similar relative to White VA-users across VAMCs at all performance levels, disparities were exacerbated for AIAN and Native Hawaiian or Other Pacific Islander VA-users in bottom-performing VAMCs. Equity remains an issue even in facilities providing overall high-quality care. Integrating equity as a component of quality measures can incentivize greater focus on equity in quality improvement., Competing Interests: Conflicts of interest Please see ICMJE form(s) for author conflicts of interest. These have been provided as supplementary materials., (Published by Oxford University Press on behalf of Project HOPE - The People-To-People Health Foundation, Inc. 2024.)

Objective: We assessed equity in the uptake of remote foot temperature monitoring (RTM) for amputation prevention throughout a large, integrated US healthcare system between 2019 and 2021, including comparisons across facilities and between patients enrolled and eligible patients not enrolled in RTM focusing on the Reach and Adoption dimensions of the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework., Material and Methods: To assess whether there was equitable use of RTM across facilities, we examined distributions of patient demographic, geographic, and facility characteristics across facility RTM use categories (e.g., no RTM use, and low, moderate, and high RTM use) among all eligible patients (n = 46,294). Second, to understand whether, among facilities using RTM, there was equitable enrollment of patients in RTM, we compared characteristics of patients enrolled in RTM (n = 1066) relative to a group of eligible patients not enrolled in RTM (n = 27,166) using logistic regression and including all covariates., Results: RTM use increased substantially from an average of 11 patients per month to over 40 patients per month between 2019 and 2021. High-use RTM facilities had higher complexity and a lower ratio of patients per podiatrist but did not have consistent evidence of better footcare process measures. Among facilities offering RTM, enrollment varied by age, was inversely associated with Black race (vs. white), low income, living far from specialty care, and being in the highest quartiles of telehealth use prior to enrollment. Enrollment was positively associated with having osteomyelitis, Charcot foot, a partial foot amputation, BMI≥30 kg/m2, and high outpatient utilization., Conclusions: RTM growth was concentrated in a small number of higher-resourced facilities, with evidence of lower enrollment among those who were Black and lived farther from specialty care. Future studies are needed to identify and address barriers to uptake of new interventions like RTM to prevent exacerbating existing ulceration and amputation disparities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Amnestic mild cognitive impairment (aMCI) is a predementia stage of Alzheimer's disease associated with dysfunctional episodic memory and limited treatment options. We aimed to characterize feasibility, clinical, and biomarker effects of noninvasive neurostimulation for aMCI. 13 individuals with aMCI received eight 60-minute sessions of 40-Hz (gamma) transcranial alternating current stimulation (tACS) targeting regions related to episodic memory processing. Feasibility, episodic memory, and plasma Alzheimer's disease biomarkers were assessed. Neuroplastic changes were characterized by resting-state functional connectivity (RSFC) and neuronal excitatory/inhibitory balance. Gamma tACS was feasible and aMCI participants demonstrated improvement in multiple metrics of episodic memory, but no changes in biomarkers. Improvements in episodic memory were most pronounced in participants who had the highest modeled tACS-induced electric fields and exhibited the greatest changes in RSFC. Increased RSFC was also associated with greater hippocampal excitability and higher baseline white matter integrity. This study highlights initial feasibility and the potential of gamma tACS to rescue episodic memory in an aMCI population by modulating connectivity and excitability within an episodic memory network., Competing Interests: Disclosure statement A.G. is a scientific advisor for Neuroelectrics, which is the company that makes the neurostimulation device used in the current study., (Published by Elsevier Inc.)

Objective: We evaluated the effectiveness of remote foot temperature monitoring (RTM) in the Veterans Affairs health care system., Research Design and Methods: We conducted a retrospective cohort study that included 924 eligible patients enrolled in RTM between 2019 and 2021 who were matched up to 3:1 to 2,757 nonenrolled comparison patients. We used conditional Cox regression to estimate adjusted cause-specific hazard ratios (aHRs) and corresponding 95% CIs for lower-extremity amputation (LEA) as the primary outcome and all-cause hospitalization and death as secondary outcomes., Results: RTM was not associated with LEA incidence (aHR 0.92, 95% CI 0.62-1.37) or all-cause hospitalization (aHR 0.97, 95% CI 0.82-1.14) but was inversely associated (reduced risk) with death (aHR 0.63, 95% CI 0.49-0.82)., Conclusions: This study does not provide support that RTM reduces the risk of LEA or all-cause hospitalization in individuals with a history of diabetic foot ulcer. Randomized controlled trials can overcome important limitations., (© 2023 by the American Diabetes Association.)

As novel coronavirus 2019 disease (COVID-19) began to spread across the United States in early 2020, health care systems faced extreme demands on resources. As the country's largest single-payer health care system, the U.S. Department of Veterans Affairs (VA) was uniquely positioned to study how the virus impacted different communities and work to improve care provided to all. Early on, a literature review of prior epidemics revealed that occupational exposures and an inability to socially distance could impact some groups more than others. The VA's Office of Health Equity leveraged a general sense of community to create a collaborative research space and a dedicated analytic space to inform pandemic operations. VA researchers and operations staff were able to quickly share information and respond to updates to produce accurate and reliable publications for medical professionals and the general public. Partnerships with VA Medical Centers and Veteran Service Organizations helped to increase communication across the nation and determine the most critical needs. Although COVID-19 was dynamic in nature, VA's intentional examination of social and structural factors was crucial in informing a more equitable approach. Moving forward, these inequities must be intentionally addressed in future pandemic responses., Competing Interests: No competing financial interests exist., (© Sarah C. Leder et al., 2023; Published by Mary Ann Liebert, Inc.)

Individuals with multi-domain amnestic mild cognitive impairment (md-aMCI) have an elevated risk of dementia and need interventions that may retain or remediate cognitive function. In a feasibility pilot study, 30 older adults aged 60-80 years with md-aMCI were randomized to 8 sessions of transcranial alternating current stimulation (tACS) with simultaneous cognitive control training (CCT). The intervention took place within the participant's home without direct researcher assistance. Half of the participants received prefrontal theta tACS during CCT and the other half received control tACS. We observed high tolerability and adherence for at-home tACS + CCT. Within 1-week, only those who received theta tACS exhibited improved attentional abilities. Neuromodulation is feasible for in-home settings, which can be conducted by the patient, thereby enabling treatment in difficult to reach populations. TACS with CCT may facilitate cognitive control abilities in md-aMCI, but research in a larger population is needed to validate efficacy., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: Evaluate self-reported electronic screening ( eScreening ) in a VA Transition Care Management Program (TCM) to improve the accuracy and completeness of administrative ethnicity and race data., Materials and Methods: We compared missing, declined, and complete (neither missing nor declined) rates between (1) TCM-eScreening (ethnicity and race entered into electronic tablet directly by patient using eScreening), (2) TCM-EHR (Veteran-completed paper form plus interview, data entered by staff), and (3) Standard-EHR (multiple processes, data entered by staff). The TCM-eScreening ( n  = 7113) and TCM-EHR groups ( n  = 7113) included post-9/11 Veterans. Standard-EHR Veterans included all non-TCM Gulf War and post-9/11 Veterans at VA San Diego ( n  = 92 921)., Results: Ethnicity : TCM-eScreening had lower rates of missingness than TCM-EHR and Standard-EHR (3.0% vs 5.3% and 8.6%, respectively, P  < .05), but higher rates of "decline to answer" (7% vs 0.5% and 1.2%, P  < .05). TCM-EHR had higher data completeness than TCM-eScreening and Standard-EHR (94.2% vs 90% and 90.2%, respectively, P  < .05). Race : No differences between TCM-eScreening and TCM-EHR for missingness (3.5% vs 3.4%, P  > .05) or data completeness (89.9% vs 91%, P  > .05). Both had better data completeness than Standard-EHR ( P  < .05), which despite the lowest rate of "decline to answer" (3%) had the highest missingness (10.3%) and lowest overall completeness (86.6%). There was strong agreement between TCM-eScreening and TCM-EHR for ethnicity (Kappa = .92) and for Asian, Black, and White Veteran race (Kappas = .87 to .97), but lower agreement for American Indian/Alaska Native (Kappa = .59) and Native Hawaiian/Other Pacific Islander (Kappa = .50) Veterans., Conculsions: eScreening is a promising method for improving ethnicity and race data accuracy and completeness in VA., Competing Interests: None declared., (Published by Oxford University Press on behalf of the American Medical Informatics Association 2023.)

The dentate gyrus (DG) is an integral portion of the hippocampal formation, and it is composed of three layers. Quantitative magnetic resonance (MR) imaging has the capability to map brain tissue microstructural properties which can be exploited to investigate neurodegeneration in Alzheimer's disease (AD). However, assessing subtle pathological changes within layers requires high resolution imaging and histological validation. In this study, we utilized a 16.4 Tesla scanner to acquire ex vivo multi-parameter quantitative MRI measures in human specimens across the layers of the DG. Using quantitative diffusion tensor imaging (DTI) and multi-parameter MR measurements acquired from AD (N = 4) and cognitively normal control (N = 6) tissues, we performed correlation analyses with histological measurements. Here, we found that quantitative MRI measures were significantly correlated with neurofilament and phosphorylated Tau density, suggesting sensitivity to layer-specific changes in the DG of AD tissues., 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. Published by Elsevier Inc.)

Age-related declines in cognitive control, an ability critical in most daily tasks, threaten individual independence. We previously showed in both older and younger adults that transcranial alternating current stimulation (tACS) can improve cognitive control, with effects observed across neural regions distant from the stimulated site and frequencies outside the stimulated range. Here, we assess network-level changes in neural activity that extend beyond the stimulated site and evaluate anatomical pathways that subserve these effects. We investigated the potential to rescue cognitive control in aging using prefrontal (F3-F4) theta (6 Hz) or control (1 Hz) tACS while older adults engaged in a cognitive control video game intervention on three consecutive days. Functional connectivity was assessed with EEG by measuring daily changes in frontal-posterior phase-locking values (PLV) from the tACS-free baseline. Structural connectivity was measured using MRI diffusion tractography data collected at baseline. Theta tACS improved multitasking performance, and individual gains reflected a dissociation in daily PLV changes, where theta tACS strengthened PLV and control tACS reduced PLV. Strengthened alpha-beta PLV in the theta tACS group correlated positively with inferior longitudinal fasciculus and corpus callosum body integrity, and further explained multitasking gains. These results demonstrate that theta tACS can improve cognitive control in aging by strengthening functional connectivity, particularly in higher frequency bands. However, the extent of functional connectivity gains is limited by the integrity of structural white matter tracts. Given that advanced age is associated with decreased white matter integrity, results suggest that the deployment of tACS as a therapeutic is best prior to advanced age., Competing Interests: Competing Interests AG is a scientific advisor for Neuroelectrics, which makes the neurostimulation device employed in the current study. As such, AG was not involved in data collection or analysis. TZ is a scientific advisor for HUMM, which makes a neurostimulation device not used in the current study., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Marginalized communities have been disproportionally impacted by SARS-CoV-2. How the associations between social determinants of health and the risk of SARS-CoV-2 infection shifted across time is unknown. In this evaluation, we examine individual-level social determinants of health as social risk factors for SARS-CoV-2 infection across the first 12 months of the pandemic among US Veterans., Methods: We conducted a retrospective cohort analysis of 946,358 Veterans who sought testing or treatment for SARS-CoV-2 infection in U.S. Department of Veterans Affairs medical facilities. We estimated risk ratios for testing positive by social risk factors, adjusting for demographics, comorbidities, and time. Adjusted models were stratified by pandemic phase to assess temporal fluctuations in social risks., Results: Approximately 19% of Veterans tested positive for SARS-CoV-2. Larger household size was a persistent risk factor and this association increased over time. Early in the pandemic, lower county-level population density was associated with lower SARS-CoV-2 infection risk, but between June 1 and August 31, 2020, this trend reversed., Conclusions: Temporal fluctuations in social risks associated with Veterans' SARS-CoV-2 infection suggest the need for ongoing, real-time tracking as the social and medical environment continues to evolve., (Published by Elsevier Inc.)

Introduction: Maintaining accurate race and ethnicity data among patients of the Veterans Affairs (VA) healthcare system has historically been a challenge. This work expands on previous efforts to optimize race and ethnicity values by combining multiple VA data sources and exploring race- and ethnicity-specific collation algorithms., Materials and Methods: We linked VA patient data from 2000 to 2018 with race and ethnicity data from four administrative and electronic health record sources: VA Medical SAS files (MedSAS), Corporate Data Warehouse (CDW), VA Centers for Medicare extracts (CMS), and VA Defense Identity Repository Data (VADIR). To assess the accuracy of each data source, we compared race and ethnicity values to self-reported data from the Survey of Health Experiences of Patients (SHEP). We used Cohen's Kappa to assess overall (holistic) source agreement and positive predictive values (PPV) to determine the accuracy of sources for each race and ethnicity separately., Results: Holistic agreement with SHEP data was excellent (K > 0.80 for all sources), while race- and ethnicity-specific agreement varied. All sources were best at identifying White and Black users (average PPV = 0.94, 0.93, respectively). When applied to the full VA user population, both holistic and race-specific algorithms substantially reduced unknown values, as compared to single-source methods., Conclusions: Combining multiple sources to generate race and ethnicity values improves data accuracy among VA patients. Based on the overall agreement with self-reported data, we recommend using non-missing values from sources in the following order to fill in race values-SHEP, CMS, CDW, MedSAS, and VADIR-and in the following order to fill in ethnicity values-SHEP, CDW, MedSAS, VADIR, and CMS., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

The use of noninvasive transcranial electrical stimulation (tES) has rapidly increased over the past two decades. Yet, tES continues to be largely implemented in laboratory and rehabilitation settings, thereby limiting accessibility to the broader population. We have previously demonstrated that transcranial alternating current stimulation (tACS) in the theta (4-7 Hz) band improves cognitive control, such as multitasking, in younger adults following a single tACS session, as well as in older adults following three tACS sessions. Here, the goal was to extend our in-lab results by (1) assessing the feasibility for at-home tACS and (2) evaluating whether five tACS sessions may yield continuing improvements in multitasking ability in young adults. Participants (aged 18 - 34 years) received bilateral prefrontal tACS while engaged in an adaptive multitasking training over five consecutive days in their home settings. Participants were randomly assigned to receive either 20-minutes of theta or delta tACS during daily multitasking training. Prior to and on the day immediately following five days of tACS, we assessed performance on single task, multitask, and sustained attention ability with analyses of variance statistics. 92.1% of participants were able to self-administer tACS at home without researcher assistance. However, we observed that both theta and delta tACS groups exhibited improvements in both single and multitask performance. Compared to previously collected data, five days of theta tACS was comparable to one day of theta tACS. However, theta tACS has continued benefits in older, but not younger adults as evidenced by previous research. Both groups similarly improved in sustained attention. These results demonstrate that laboratory paradigms utilizing neurostimulation can be effectively deployed in a home environment without direct support from research personnel. Moreover, these results suggest that while theta tACS may facilitate multitasking improvements over one session, multiple sessions of theta tACS results in diminishing returns in young adults. Additional research will be required to confirm if delta activity plays an important role in multitasking ability., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

A primary goal of translational neuroscience is to identify the neural mechanisms of age-related cognitive decline and develop protocols to maximally improve cognition. Here, we demonstrate how interventions that apply noninvasive neurostimulation to older adults improve working memory (WM). We found that one session of sham-controlled transcranial direct current stimulation (tDCS) selectively improved WM in older adults with more education, extending earlier work and underscoring the importance of identifying individual predictors of tDCS responsivity. Improvements in WM were associated with two distinct electrophysiological signatures. First, a broad enhancement of theta network synchrony tracked improvements in behavioral accuracy, with tDCS effects moderated by education level. Further analysis revealed that accuracy dynamics reflected an anterior-posterior network distribution regardless of cathode placement. Second, specific enhancements of theta-gamma phase-amplitude coupling (PAC) reflecting tDCS current flow tracked improvements in reaction time (RT). RT dynamics further explained inter-individual variability in WM improvement independent of education. These findings illuminate theta network synchrony and theta-gamma PAC as distinct but complementary mechanisms supporting WM in aging. Both mechanisms are amenable to intervention, the effectiveness of which can be predicted by individual demographic factors., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Equitable COVID-19 vaccine access is imperative to mitigating negative COVID-19 impacts among racial/ethnic minorities. U.S. racial/ethnic minorities have lower COVID-19 vaccination rates than Whites despite higher COVID-19 death/case rates. The Veterans Health Administration provides the unique context of a managed care system with few access barriers. This study evaluates race/ethnicity as a predictor of Veterans Health Administration COVID-19 vaccination., Methods: The cohort was composed of Veterans Health Administration outpatient users aged ≥65 years (N=3,474,874). COVID-19 vaccination was assessed between December 14, 2020 and February 23, 2021. Multivariable logistic regressions were conducted, controlling for demographics, medical comorbidity, and influenza vaccination history. Proximity to Indian Health Service Contract Health Service Delivery Areas was tested as a moderator. Data analyses were conducted during 2021., Results: Blacks (OR=1.28, 95% CI=1.17, 1.40), Hispanics (OR=1.15, 95% CI=1.05, 1.25), and Asians (OR=1.21, 95% CI=1.02, 1.43) were more likely than Whites to receive Veterans Health Administration COVID-19 vaccinations. American Indian/Alaska Natives were less likely than Whites to receive Veterans Health Administration COVID-19 vaccinations, but only those residing in Contract Health Service Delivery Area counties (OR= 0.58, 95% CI= 0.47, 0.72). Influenza vaccine history positively predicted COVID-19 vaccine uptake (OR= 2.28, 95% CI=2.22, 2.34)., Conclusions: In the Veterans Health Administration, compared with the general U.S. population, COVID-19 vaccine receipt is higher among most racial/ethnic minority groups than Whites, suggesting reduced vaccination barriers . The Indian Health Service may provide a safety net for American Indian/Alaska Native populations. Addressing vaccination access barriers in non-Veterans Health Administration settings can potentially reduce racial/ethnic disparities., (Published by Elsevier Inc.)

Racial/ethnic disparities in coronavirus disease 2019 (COVID-19) hospitalization and mortality have emerged in the United States, but less is known about whether similar differences exist in testing, and how this changed as COVID-19 knowledge and policies evolved. We examined racial/ethnic variations in COVID-19 testing over time among veterans who sought care for COVID-19 symptoms or exposure. In the national population of all Veterans who sought Veterans Health Administration (VHA) care for COVID-19 symptoms or exposure (n = 913,806), we conducted multivariate logistic regressions to explore race/ethnicity-by-time period differences in testing from 3/1/2020-11/25/2020, and calculated predicted probabilities by race/ethnicity and time period. Early in the pandemic (3/1/2020-4/6/2020) when testing was limited and there was less awareness of racial/ethnic disparities, non-Hispanic Black, Hispanic, and other non-White racial/ethnic minority Veterans who sought care from VHA for COVID-19 symptoms or exposure were more likely than non-Hispanic White Veterans to receive a COVID-19 test (p < 0.05). In subsequent time periods (4/7/2020-11/25/2020), testing was similar among all racial/ethnic groups. Among Veterans with COVID-19 symptoms or exposure, non-Hispanic Black and Hispanic patients were just as likely, and in some cases, more likely, to receive a COVID-19 test versus non-Hispanic White patients. The United States faced testing shortages at the start of the third wave of the pandemic; additional shortages are likely to emerge as the pandemic continues to peak and ebb. It is important to ensure that racial/ethnic minorities and others at greater risk for infection continue to have access to COVID-19 testing with each of these peaks., 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.

The repetitive sequences of DNA centromeric regions form the structural basis for kinetochore assembly. Recently they were found to be transcriptionally active in mitosis, with their RNAs providing noncoding functions. Here we explore the role, in mouse oocytes, of transcripts generated from within the minor satellite repeats. Depletion of minor satellite transcripts delayed progression through meiosis I by activation of the spindle assembly checkpoint. Arrested oocytes had poorly congressed chromosomes, and centromeres were frequently split by microtubules. Thus, we have demonstrated that the centromeric RNA plays a specific role in female meiosis I compared with mitosis and is required for maintaining the structural integrity of centromeres. This may contribute to the high aneuploidy rates observed in female meiosis., (© 2021 Wu et al.)

Background: Noninvasive transcranial electrical stimulation (tES) research has been plagued with inconsistent effects. Recent work has suggested neuroanatomical and neurophysiological variability may alter tES efficacy. However, direct evidence is limited., Objective: We have previously replicated effects of transcranial alternating current stimulation (tACS) on improving multitasking ability in young adults. Here, we attempt to assess whether these stimulation parameters have comparable effects in older adults (aged 60-80 years), which is a population known to have greater variability in neuroanatomy and neurophysiology. It is hypothesized that this variability in neuroanatomy and neurophysiology will be predictive of tACS efficacy., Methods: We conducted a pre-registered study where tACS was applied above the prefrontal cortex (between electrodes F3-F4) while participants were engaged in multitasking. Participants were randomized to receive either 6-Hz (theta) tACS for 26.67 min daily for three days (80 min total; Long Exposure Theta group), 6-Hz tACS for 5.33 min daily (16-min total; Short Exposure Theta group), or 1-Hz tACS for 26.67 min (80 min total; Control group). To account for neuroanatomy, magnetic resonance imaging data was used to form individualized models of the tACS-induced electric field (EF) within the brain. To account for neurophysiology, electroencephalography data was used to identify individual peak theta frequency., Results: Results indicated that only in the Long Theta group, performance change was correlated with modeled EF and peak theta frequency. Together, modeled EF and peak theta frequency accounted for 54%-65% of the variance in tACS-related performance improvements, which sustained for a month., Conclusion: These results demonstrate the importance of individual differences in neuroanatomy and neurophysiology in tACS research and help account for inconsistent effects across studies., Competing Interests: Declaration of competing interest T.Z. is a scientific advisor for HUMM, which makes a neurostimulation device not used in the current study. A.G. is a scientific advisor for Neuroelectrics, which makes the neurostimulation device employed in the current study. As such, A.G. was not involved in data collection or analysis., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective. Intracortical microelectrode arrays (MEA) can be used as part of a brain-machine interface system to provide sensory feedback control of an artificial limb to assist persons with tetraplegia. Variability in functionality of electrodes has been reported but few studies in humans have examined the impact of chronic brain tissue responses revealed postmortem on electrode performance in vivo. Approach. In a tetraplegic man, recording MEAs were implanted into the anterior intraparietal area and Brodmann's area 5 (BA5) of the posterior parietal cortex and a recording and stimulation array was implanted in BA1 of the primary somatosensory cortex (S1). The participant expired from unrelated causes seven months after MEA implantation. The underlying tissue of two of the three devices was processed for histology and electrophysiological recordings were assessed. Main results. Recordings of neuronal activity were obtained from all three MEAs despite meningeal encapsulation. However, the S1 array had a greater encapsulation, yielded lower signal quality than the other arrays and failed to elicit somatosensory percepts with electrical stimulation. Histological examination of tissues underlying S1 and BA5 implant sites revealed localized leptomeningeal proliferation and fibrosis, lymphocytic infiltrates, astrogliosis, and foreign body reaction around the electrodes. The BA5 recording site showed focal cerebral microhemorrhages and leptomeningeal vascular ectasia. The S1 site showed focal tissue damage including vascular recanalization, neuronal loss, and extensive subcortical white matter necrosis. The tissue response at the S1 site included hemorrhagic-induced injury suggesting a likely mechanism for reduced function of the S1 implant. Significance. Our findings are similar to those from animal studies with chronic intracortical implants and suggest that vascular disruption and microhemorrhage during device implantation are important contributors to overall array and individual electrode performance and should be a topic for future device development to mitigate tissue responses. Neurosurgical considerations are also discussed., (Creative Commons Attribution license.)

Studies documenting coronavirus disease 2019 (COVID-19) racial/ethnic disparities in the United States were limited to data from the initial few months of the pandemic, did not account for changes over time, and focused primarily on Black and Hispanic minority groups. To fill these gaps, we examined time trends in racial/ethnic disparities in COVID-19 infection and mortality. We used the Veteran Health Administration's (VHA) national database of veteran COVID-19 infections over three time periods: 3/1/2020-5/31/2020 (spring); 6/1/2020-8/31/2020 (summer); and 9/1/2020-11/25/2020 (fall). We calculated COVID-19 infection and mortality predicted probabilities from logistic regression models that included time period-by-race/ethnicity interaction terms, and controlled for age, gender, and prior diagnosis of CDC risk factors. Racial/ethnic groups at higher risk for COVID-19 infection and mortality changed over time. American Indian/Alaskan Natives (AI/AN), Blacks, Hispanics, and Native Hawaiians/Other Pacific Islanders experienced higher COVID-19 infections compared to Whites during the summertime. There were mortality disparities for Blacks in springtime, and AI/ANs, Asians, and Hispanics in summertime. Policy makers should consider the dynamic nature of racial/ethnic disparities as the pandemic evolves, and potential effects of risk mitigation and other (e.g., economic) policies on these disparities. Researchers should consider how trends in disparities change over time in other samples.

Purpose: Currently, there is little consensus on management of the in situ gallbladder of patients undergoing gastric bypass. Our aim was to evaluate outcomes of selective concomitant cholecystectomy (CCY) and long-term biliary outcomes after Roux-en-Y gastric bypass (RYGB)., Materials and Methods: We performed a retrospective analysis of patients undergoing laparoscopic RYGB (LRYGB) between 2008 and 2018. Chi-square, Fisher's exact, or Wilcoxon rank-sum tests were used to compare outcomes. Concomitant CCY was performed on a selective basis., Results: Three thousand and four patients underwent a RYGB (LRYGB n = 2458, open RYGB n = 546). Fifty-two percent (n = 1670) of patients had undergone CCY at any stage. Thirty-one percent of patients (n = 933) had CCY prior to RYGB, 13% (n = 403) had a concomitant CCY and 13% (n = 214) of the remainder required interval CCY. In the LRYGB subgroup, 29.9% (n = 735) had a prior CCY; 12.9% (n = 202) of those with an in situ gallbladder required interval CCY. Those who underwent concomitant CCY/LRYGB (n = 328) were compared with LRYGB alone (n = 1231). The concomitant CCY group was significantly older and had higher percentage of females, higher preoperative BMI, higher Charlson Comorbidity Index, and a higher medication count. There was no significant difference in BMI nadir, length of stay, complications, or mortality. Interval CCY had a higher incidence of CCY-related complications., Conclusion: Our study suggests a higher percentage of bariatric patients with in situ gallbladders will undergo interval CCY than documented in recently published guidelines. Concomitant CCY can be performed without an increase in length of stay or complications. Interval CCY may be associated with a higher complication rate.

Auditory gamma-band (>30 Hz) activity is a biomarker of cortical excitation/inhibition (E/I) balance in autism, schizophrenia, and bipolar disorder. We provide a comprehensive account of the effects of transcranial alternating current stimulation (tACS) and transcranial direct current stimulation (tDCS) on gamma responses. Forty-five healthy young adults listened to 40-Hz auditory click trains while electroencephalography (EEG) data were collected to measure stimulus-related gamma activity immediately before and after 10 min of 1 mA tACS (40 Hz), tDCS, or sham stimulation to left auditory cortex. tACS, but not tDCS, increased gamma power and phase locking to the auditory stimulus. However, both tACS and tDCS strengthened the gamma phase connectome, and effects persisted beyond the stimulus. Finally, tDCS strengthened the coupling of gamma activity to alpha oscillations after termination of the stimulus. No effects were observed in prestimulus gamma power, the gamma amplitude connectome, or any band-limited alpha measure. Whereas both stimulation techniques synchronize gamma responses between regions, tACS also tunes the magnitude and timing of gamma responses to the stimulus. Results reveal dissociable neurophysiological changes following tACS and tDCS and demonstrate that clinical biomarkers can be altered with noninvasive neurostimulation, especially frequency-tuned tACS. NEW & NOTEWORTHY Gamma frequency-tuned transcranial alternating current stimulation (tACS) adjusts the magnitude and timing of auditory gamma responses, as compared with both sham stimulation and transcranial direct current stimulation (tDCS). However, both tACS and tDCS strengthen the gamma phase connectome, which is disrupted in numerous neurological and psychiatric disorders. These findings reveal dissociable neurophysiological changes following two noninvasive neurostimulation techniques commonly applied in clinical and research settings.

Despite considerable interest in enhancing, preserving, and rehabilitating working memory (WM), efforts to elicit sustained behavioral improvements have been met with limited success. Here, we paired WM training with transcranial direct current stimulation (tDCS) to the frontoparietal network over four days. Active tDCS enhanced WM performance by modulating interactions between frontoparietal theta oscillations and gamma activity, as measured by pre- and post-training high-density electroencephalography (EEG). Increased phase-amplitude coupling (PAC) between the prefrontal stimulation site and temporo-parietal gamma activity explained behavioral improvements, and was most effective when gamma occurred near the prefrontal theta peak. These results demonstrate for the first time that tDCS-linked WM training elicits lasting changes in behavior by optimizing the oscillatory substrates of prefrontal control., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier Inc.)

Working memory (WM) can be improved after repeated training sessions paired with noninvasive neurostimulation techniques. Previously, we reported that WM training paired with tDCS succeeded behaviorally by enhancing anterior-posterior theta phase coherence and reducing alpha power. Here, in two experiments we tested several theta and alpha frequencies and two transcranial alternating current stimulation (tACS) montages in an effort to shortcut WM training while preserving behavioral gains. In Experiment 1, in separate sessions participants received online tACS at two frequencies derived from the previous study with the respective goal of improving and impairing WM performance. We selected the mean group peak value theta (7 Hz) to benefit WM and alpha (11 Hz) to impair WM. Stimulation (tACS) over right frontoparietal sites (F4-P4) during 3-back WM tasks (object, spatial) produced no behavioral consequences. In Experiment 2 we stimulated at a slower theta frequency (4.5 Hz), which was also significant in our prior study, and tested whether frontoparietal or bifrontal montages would be more effective at improving WM. This experiment revealed selectively improved object WM after right frontoparietal tACS alone. In summary, one session of tACS failed to produce the magnitude or breadth of WM gains observed after 4-10 tDCS-WM training sessions. In short, despite looking for loopholes we found little tACS savings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The selective estrogen receptor modulator tamoxifen increases extracellular dopamine in vivo and acts as a neuroprotectant in models of dopamine neurotoxicity. We investigated the effect of tamoxifen on dopamine transporter (DAT)-mediated dopamine uptake, dopamine efflux, and [ 3 H]WIN 35,428 [(-)-2- β -carbomethoxy-3- β -(4-fluorophenyl)tropane] binding in rat striatal tissue. Tamoxifen dose-dependently blocked dopamine uptake (54% reduction at 10 μ M) and amphetamine-stimulated efflux (59% reduction at 10 μ M) in synaptosomes. It also produced a small but significant reduction in [ 3 H]WIN 35,428 binding in striatal membranes, indicating a weak interaction with the substrate binding site in the DAT. Biotinylation and cysteine accessibility studies indicated that tamoxifen stabilizes the outward-facing conformation of the DAT in a cocaine-like manner and does not affect surface expression of the DAT. Additional studies with mutant DAT constructs D476A and I159A suggested a direct interaction between tamoxifen and a secondary substrate binding site of the transporter. Locomotor studies revealed that tamoxifen attenuates amphetamine-stimulated hyperactivity in rats but has no depressant or stimulant activity in the absence of amphetamine. These results suggest a complex mechanism of action for tamoxifen as a regulator of the DAT. Due to its effectiveness against amphetamine actions and its central nervous system permeant activity, the tamoxifen structure represents an excellent starting point for a structure-based drug-design program to develop a pharmacological therapeutic for psychostimulant abuse., (Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.)

Mouse female meiotic spindles assemble from acentriolar microtubule-organizing centers (aMTOCs) that fragment into discrete foci. These are further sorted and clustered to form spindle poles, thus providing balanced forces for faithful chromosome segregation. To assess the impact of aMTOC biogenesis on spindle assembly, we genetically induced their precocious fragmentation in mouse oocytes using conditional overexpression of Plk4, a master microtubule-organizing center regulator. Excessive microtubule nucleation from these fragmented aMTOCs accelerated spindle assembly dynamics. Prematurely formed spindles promoted the breakage of three different fragilized bivalents, generated by the presence of recombined Lox P sites. Reducing the density of microtubules significantly diminished the extent of chromosome breakage. Thus, improper spindle forces can lead to widely described yet unexplained chromosomal structural anomalies with disruptive consequences on the ability of the gamete to transmit an uncorrupted genome., (© 2018 Manil-Ségalen et al.)

Initiated by luteinizing hormone and finalized by the fertilizing sperm, the mammalian oocyte completes its two meiotic divisions. The first division occurs in the mature Graafian follicle during the hours preceding ovulation and culminates in an extreme asymmetric cell division and the segregation of the two pairs of homologous chromosomes. The newly created mature egg rearrests at metaphase of the second meiotic division prior to ovulation and only completes meiosis following a Ca 2+ signal initiated by the sperm at gamete fusion. Here, we review the cellular events that govern the passage of the oocyte through meiosis I with a focus on the role of the spindle assembly checkpoint in regulating its timing. In meiosis II, we examine how the egg achieves its arrest and how the fertilization Ca 2+ signal allows the initiation of embryo development., (© 2018 The Author(s).)

In the first meiotic division (MI) of oocytes, the cortically positioned spindle causes bivalent segregation in which only the centre-facing homologue pairs are retained. 'Selfish' chromosomes are known to exist, which bias their spindle orientation and hence retention in the egg, a process known as 'meiotic drive'. Here we report on this phenomenon in oocytes from F 1 hybrid mice, where parental strain differences in centromere size allows distinction of the two homologue pairs of a bivalent. Bivalents with centromere and kinetochore asymmetry show meiotic drive by rotating during prometaphase, in a process dependent on aurora kinase activity. Cortically positioned homologue pairs appear to be under greater stretch than their centre-facing partners. Additionally the cortex spindle-half contain a greater density of tubulin and microtubule organising centres. A model is presented in which meiotic drive is explained by the impact of microtubule force asymmetry on chromosomes with different sized centromeres and kinetochores.

Working memory (WM) permits maintenance of information over brief delays and is an essential executive function. Unfortunately, WM is subject to age-related decline. Some evidence supports the use of transcranial direct current stimulation (tDCS) to improve visual WM. A gap in knowledge is an understanding of the mechanism characterizing these tDCS linked effects. To address this gap, we compared the effects of two tDCS montages designed on visual working memory (VWM) performance. The bifrontal montage was designed to stimulate the heightened bilateral frontal activity observed in aging adults. The unilateral frontoparietal montage was designed to stimulate activation patterns observed in young adults. Participants completed three sessions (bilateral frontal, right frontoparietal, sham) of anodal tDCS (20 min, 2 mA). During stimulation, participants performed a visual long-term memory (LTM) control task and a visual WM task. There was no effect of tDCS on the LTM task. Participants receiving right unilateral tDCS showed a WM benefit. This pattern was most robust in older adults with low WM capacity. To address the concern that the key difference between the two tDCS montages could be tDCS over the posterior parietal cortex (PPC), we included new analyses from a previous study applying tDCS targeting the PPC paired with a recognition VWM task. No significant main effects were found. A subsequent experiment in young adults found no significant effect of either tDCS montage on either task. These data indicate that tDCS montage, age and WM capacity should be considered when designing tDCS protocols. We interpret these findings as suggestive that protocols designed to restore more youthful patterns of brain activity are superior to those that compensate for age-related changes.

A recent study reports on five different mutations as sources of dopamine transporter (DAT) deficiency syndrome (DTDS). One of these mutations, R445C, is believed to be located on the intracellular side of DAT distal to the primary (S1) or secondary (S2) sites to which substrate binding is understood to occur. Thus, the molecular mechanism by which the R445C mutation results in DAT transport deficiency has eluded explanation. However, the recently reported X-ray structures of the endogenous amine transporters for dDAT and hSERT revealed the presence of a putative salt bridge between R445 and E428 suggesting a possible mechanism. To evaluate whether the R445C effect is a result of a salt bridge interaction, the mutants R445E, E428R, and the double mutant E428R/R445E were generated. The single mutants R445E and E428R displayed loss of binding and transport properties of the substrate [ 3 H]DA and inhibitor [ 3 H]CFT at the cell surface while the double mutant E428R/R445E, although nonfunctional, restored [ 3 H]DA and [ 3 H]CFT binding affinity to that of WT. Structure based analyses of these results led to a model wherein R445 plays a dual role in normal DAT function. R445 acts as a component of a latch in its formation of a salt bridge with E428 which holds the primary substrate binding site (S1) in place and helps enforce the inward closed protein state. When this salt bridge is broken, R445 acts as a trigger which disrupts a local polar network and leads to the release of the N-terminus from its position inducing the inward closed state to one allowing the inward open state. In this manner, both the loss of binding and transport properties of the R445C variant are explained., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The spindle assembly checkpoint (SAC) prevents chromosome missegregation by coupling anaphase onset with correct chromosome attachment and tension to microtubules. It does this by generating a diffusible signal from free kinetochores into the cytoplasm, inhibiting the anaphase-promoting complex (APC). The volume in which this signal remains effective is unknown. This raises the possibility that cell volume may be the reason the SAC is weak, and chromosome segregation error-prone, in mammalian oocytes. Here, by a process of serial bisection, we analyzed the influence of oocyte volume on the ability of the SAC to inhibit bivalent segregation in meiosis I. We were able to generate oocytes with cytoplasmic volumes reduced by 86% and observed changes in APC activity consistent with increased SAC control. However, bivalent biorientation remained uncoupled from APC activity, leading to error-prone chromosome segregation. We conclude that volume is one factor contributing to SAC weakness in oocytes. However, additional factors likely uncouple chromosome biorientation with APC activity., (© 2017 Lane and Jones.)

Working memory (WM) training paired with transcranial direct current stimulation (tDCS) can improve executive function in older adults. The unclear mechanism of tDCS likely depends on tDCS intensity, and task relevant genetic factors (e.g., for WM: COMT val 158 met, DAT, BDNF val 66 met). Higher tDCS intensity does not always lead to greater cognitive gains, and genetic polymorphisms may modulate tDCS-linked WM improvements. To evaluate these factors, 137 healthy older adults provided DNA samples and received Visual and Spatial WM training paired with tDCS (sham, 1, 1.5, 2 mA). After one session of tDCS, significant group differences in WM performance were predicted by COMT val 158 met status. One month after training, there was a significant interaction of tDCS intensity, COMT genotype, and WM task. Specifically, val/val homozygotes benefited most from 1.5 mA tDCS on Visual WM and from 1 mA tDCS on Spatial WM. For met/met homozygotes, 2 mA resulted in significantly poorer performance compared to 1.5 mA on Spatial WM. While this pattern was observed with relatively small sample sizes, these data indicate that variations in COMT val 158 met may predict the nature of WM improvement after initial and longitudinal tDCS. This contributes to our understanding of the underlying mechanism by which tDCS affects behaviour.

Mouse oocytes carrying DNA damage arrest in meiosis I, thereby preventing creation of embryos with deleterious mutations. The arrest is dependent on activation of the spindle assembly checkpoint, which results in anaphase-promoting complex (APC) inhibition. However, little is understood about how this checkpoint is engaged following DNA damage. Here, we find that within minutes of DNA damage checkpoint proteins are assembled at the kinetochore, not at damage sites along chromosome arms, such that the APC is fully inhibited within 30 min. Despite this robust response, there is no measurable loss in k-fibres, or tension across the bivalent. Through pharmacological inhibition we observed that the response is dependent on Mps1 kinase, aurora kinase and Haspin. Using oocyte-specific knockouts we find the response does not require the DNA damage response kinases ATM or ATR. Furthermore, checkpoint activation does not occur in response to DNA damage in fully mature eggs during meiosis II, despite the divisions being separated by just a few hours. Therefore, mouse oocytes have a unique ability to sense DNA damage rapidly by activating the checkpoint at their kinetochores., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

There is considerable interest in maintaining working memory (WM) because it is essential to accomplish most cognitive tasks, and it is correlated with fluid intelligence and ecologically valid measures of daily living. Toward this end, WM training protocols aim to improve WM capacity and extend improvements to unpracticed domains, yet success is limited. One emerging approach is to couple WM training with transcranial direct current stimulation (tDCS). This pairing of WM training with tDCS in longitudinal designs promotes behavioral improvement and evidence of transfer of performance gains to untrained WM tasks. However, the mechanism(s) underlying tDCS-linked training benefits remain unclear. Our goal was to gain purchase on this question by recording high-density EEG before and after a weeklong WM training+tDCS study. Participants completed four sessions of frontoparietal tDCS (active anodal or sham) during which they performed a visuospatial WM change detection task. Participants who received active anodal tDCS demonstrated significant improvement on the WM task, unlike those who received sham stimulation. Importantly, this pattern was mirrored by neural correlates in spectral and phase synchrony analyses of the HD-EEG data. Notably, the behavioral interaction was echoed by interactions in frontal-posterior alpha band power, and theta and low alpha oscillations. These findings indicate that one mechanism by which paired tDCS+WM training operates is to enhance cortical efficiency and connectivity in task-relevant networks., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Daily moderate exercise (DME) and stress management are underemphasized in the care of patients with lupus nephritis (LN) due to a poor comprehensive understanding of their potential roles in controlling the inflammatory response. To investigate these effects on murine LN, disease progression was monitored with either DME or social disruption stress (SDR) induction in NZM2410/J mice, which spontaneously develop severe, early-onset LN. SDR of previously established social hierarchies was performed daily for 6 days and DME consisted of treadmill walking (8.5 m/min for 45 min/day). SDR significantly enhanced kidney disease when compared to age-matched, randomly selected control counterparts, as measured by histopathological analysis of H&E staining and immunohistochemistry for complement component 3 (C3) and IgG complex deposition. Conversely, while 88% of non-exercised mice displayed significant renal damage by 43 weeks of age, this was reduced to 45% with exercise. DME also reduced histopathology in kidney tissue and significantly decreased deposits of C3 and IgG complexes. Further examination of renal infiltrates revealed a macrophage-mediated inflammatory response that was significantly induced with SDR and suppressed with DME, which also correlated with expression of inflammatory mediators. Specifically, SDR induced IL-6, TNF-α, IL-1β, and MCP-1, while DME suppressed IL-6, TNF-α, IL-10, CXCL1, and anti-dsDNA autoantibodies. These data demonstrate that psychological stressors and DME have significant, but opposing effects on the chronic inflammation associated with LN; thus identifying and characterizing stress reduction and a daily regimen of physical activity as potential adjunct therapies to complement pharmacological intervention in the management of autoimmune disorders, including LN.