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Scientific evidence continues to demonstrate the linkage of vascular contributions to cognitive impairment and dementia such as Alzheimer's disease. In December, 2013, the Alzheimer's Association, with scientific input from the National Institute of Neurological Disorders and Stroke and the National Heart, Lung and Blood Institute from the National Institutes of Health, convened scientific experts to discuss the research gaps in our understanding of how vascular factors contribute to Alzheimer's disease and related dementia. This manuscript summarizes the meeting and the resultant discussion, including an outline of next steps needed to move this area of research forward. [ABSTRACT FROM AUTHOR]

Background: U.S. POINTER aims to test whether a multidomain lifestyle intervention focused on physical and cognitive activity, nutrition, and risk factor management reduces risk of cognitive decline in a heterogeneous population of older adults in the U.S. The study adapts the FINGER (Finnish Intervention Geriatric Study to Prevent Cognitive Impairment and Disability) interventions to fit American culture and works with community partners at 5 sites across the country to develop sustainable community‐based intervention programs. Methods: U.S. POINTER is a 2‐year RCT that is enrolling 2000 cognitively normal older adults (60‐79 years) who are at risk for decline due sedentary lifestyle, poor diet and other factors such as family history of memory impairment and suboptimum cardiovascular health. Recruitment utilizes electronic health records, as well as grassroots approaches to engage traditionally underrepresented groups. Participants are randomized to one of two lifestyle intervention groups – Self‐Guided or Structured Lifestyle Intervention – that differ in format, intensity and accountability. U.S. POINTER includes partnerships with local chapters of the Alzheimer's Association and lifestyle specialists to assist with intervention delivery. The primary outcome is 2‐year change in cognitive function measured with a composite score that permits harmonization with FINGER. Results: Recruitment began in 2019 at the vanguard site in North Carolina. Study progress at all 5 participating sites will be presented. Progress toward harmonization with FINGER and other international study teams in the WW‐FINGERS network will also be discussed. Conclusion: As a member of the WW‐FINGERS network of trials, U.S. POINTER provides an unprecedented opportunity to leverage lessons learned in FINGER and expand this work to test the generalizability of the findings to a heterogeneous American cohort with different cultural needs and practices. The results, in combination with those from other WW‐FINGERS studies, have the potential to identify a strategy to slow cognitive decline on a global scale. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest that lifestyle changes (physical exercise, Mediterranean diet adherence, cognitive stimulation, vascular risk management) may protect against cognitive decline and reduce AD pathophysiology. The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a 2‐year randomized controlled trial to evaluate whether lifestyle interventions can protect cognitive function in older adults (60‐79 years) who are at increased risk for cognitive impairment and dementia. The POINTER Imaging ancillary study will assess effects of the POINTER lifestyle interventions on neuroimaging biomarkers of AD and cerebrovascular pathophysiology, and whether baseline neuroimaging measures predict cognitive responses to the interventions. Method: The POINTER Imaging ancillary study aims to enroll 1250 participants from the five U.S. POINTER sites. Ancillary study participants will undergo PET imaging (Baseline, Month 24) to measure Aβ ([18F]Florbetaben) and tau ([18F]MK‐6240) burden, and MRI (Baseline, Months 12 & 24) to measure brain morphometry, white matter (WM) hyperintensities and microstructure, and cerebral blood flow. U.S. POINTER provides standardized cognitive, clinical, genetic (e.g. APOE), and lifestyle activity assessments, and demographics for integration with neuroimaging data. Result: The study design and methods for the POINTER Imaging ancillary study will be presented. The study will examine whether: (1) neuroimaging biomarkers at baseline (Aβ, tau, hippocampal volume, WM hyperintensities) predict intervention‐related cognitive changes and (2) biomarker outcomes are differentially modified by participation in lifestyle interventions. It will also examine changes in exploratory biomarkers (tensor‐based morphometry, microstructural integrity, microbleeds, cerebral blood flow). Conclusion: The POINTER Imaging study aims to address gaps in our understanding of how a variety of lifestyle practices (diet, exercise, cognitive stimulation and vascular risk management) influence brain health. In particular, the study will determine whether imaging measurements of AD and cerebrovascular pathophysiology are amenable to improvement with the POINTER lifestyle interventions. It also aims to determine pathological profiles of individuals who benefit most from such interventions. [ABSTRACT FROM AUTHOR]

Background Multidomain lifestyle interventions may have the potential to slow biological aging as captured by deficit accumulation frailty indices. We describe the distribution and composition of the 49-component frailty index developed by the U.S. POINTER clinical trial team of investigators and assess its cross-sectional associations with sociodemographic factors and markers chosen to be representative of behaviors targeted by the trial's multidomain interventions. Methods We draw baseline data from the 2 111 volunteers enrolled in U.S. POINTER who were ages 60–79 years and at increased risk for cognitive decline. Frailty components were grouped into 9 domains. Associations that frailty index scores and their domains had with behavioral markers were described with correlations and canonical correlation. Results The 25th, 50th, and 75th percentiles of the frailty index score distribution were 0.153, 0.189, and 0.235. Higher frailty scores tended to occur among individuals who were older, male, and living in areas of greater deprivation (all p  < .001). They were also associated with poorer self-reported diet, less physical activity, and higher Framingham risk scores (all p  < .001). Associations were diffusely distributed among the frailty component domains, indicating that no individual domain was dominating associations. Conclusions The U.S. POINTER deficit accumulation frailty index had expected relationships with sociodemographic factors and sensitivity to the behaviors targeted by the trial's interventions. Our analysis supports its use as a secondary outcome to assess whether the multidomain interventions differentially impact an established marker of biological aging. ClinicalTrials.gov Identifier: NCT03688126. [ABSTRACT FROM AUTHOR]

Hand hygiene is a crucial tool to limit the transmission of common respiratory and gastrointestinal infections. While hand sanitizers were ubiquitous early in the COVID-19 pandemic, the number of food establishments that have adequately maintained them remains unknown. Through systematic observations in 89 New York City food establishments, we found that hand sanitizer dispensers were present in only 40% of the stores, and only 23% had functional ones. This scarcity highlights the necessity of providing ongoing support to small business owners nationwide to promote and maintain primary prevention measures at all times, extending beyond periods of public health crises. [ABSTRACT FROM AUTHOR]

Purpose: As research increasingly links positive student-teacher relationships (STRs) to positive student outcomes, instruments to measure STRs have proliferated. Yet most neglect student agency and sociocultural variation in the operationalization of STRs. This study explores the specific actions teachers and students take to build positive STRs from the vantage point of a diverse group of US middle and high school students. Research Methods: Drawing on the principles of critical collaborative research, our intergenerational team of scholars engaged 84 youth participants (ages 12–18) in qualitative data generation and analysis, using novel youth-voice elicitation techniques known as the fishbone and diamond card sort. Findings: Findings highlight specific actions that a diverse group of youth believe students and teachers take to create positive STRs and foreground the importance of teacher power, student responsibility, safe classrooms, and reciprocity in STR construction. Implications: By pinpointing specific actions that teachers can take to build positive STRs, this work raises implications for teacher education and professional development, especially as schools struggle to regain ground with students in the wake of COVID-19 disruptions. In addition, the study demonstrates how engaging youth as partners in qualitative research can help improve the conduct and products of empirical research in education, offering a model for the field of youth validation processes. [ABSTRACT FROM AUTHOR]

Objective: To explore the experiences and care preferences of women with chronic pelvic pain, with or without a history of sexual trauma, seeking gynaecological care. Design: Qualitative study. Setting: Ambulatory endometriosis centre. Population or Sample: Women aged 18–55 years with chronic pelvic pain. Methods: Baseline demographics and sexual trauma history were obtained, and participants were assigned to focus groups according to a positive (four groups, 13 participants) or negative (two groups, nine participants) screen for a history of sexual trauma. The focus groups were led by a clinical psychologist and a gynaecological surgeon and consisted of semi‐structured interviews. The interviews were audio‐recorded and transcribed, and the transcripts were coded in NVivo 12. Main outcome measures: Content analysis was used to derive themes according to the participants' own words. Results: Participants with chronic pelvic pain, with or without a history of sexual trauma, experienced delay in diagnosis and repetitive dismissals by clinicians. Participants' experiences of dismissals included: clinicians not listening, insufficient allocation of time to appointments and perceived redundant medical testing (i.e. sexually transmitted infection testing, urine cultures, ultrasounds). Participants identified clinician interactions as pivotal in coping with both pelvic pain and sexual abuse. Participants also provided feedback regarding trauma‐informed practices and care delivery specific to patients with chronic pelvic pain. Conclusion: Patients with chronic pelvic pain, with or without a history of sexual trauma, report negative experiences when interacting with the healthcare system. They have clear needs and preferences regarding gynaecological care and provide feasible suggestions for improving care delivery. This article includes Author Insights, a video abstract available at: https://vimeo.com/775029350 [ABSTRACT FROM AUTHOR]

The period of middle adulthood presents people with self-actualization challenges related, among others, to their religious beliefs and sexual satisfaction. The aim of this study was to explore the associations between religiosity, nonconformity and sexual satisfaction, as well as to examine whether nonconformity moderates the relationship between religiosity and sexual satisfaction in middle adulthood. The following questionnaires were used: the Religious Meaning System Questionnaire, the Sexual Satisfaction Questionnaire, and the Creative Behavior Questionnaire CBQIII. A series of regression analyses using Hayes PROCESS macro was run to test the models in a sample of 667 middle adults aged between 35 and 55 (M = 42.62; SD = 5.37). The analyses revealed significant relationships between the variables. The religious meaning system showed negative correlations with both nonconformity and sexual satisfaction, whereas nonconformity was positively correlated with sexual satisfaction. An interaction effect of religiosity and nonconformity on sexual satisfaction, when controlling for gender and age, was also demonstrated. More specifically, religiosity was negatively related to sexual satisfaction in individuals with a high level of nonconformity. By contrast, for low and average levels of nonconformity, the relationship between religiosity and sexual satisfaction was insignificant. The results suggest that religiosity may interact with nonconformity when predicting the intensity of sexual satisfaction of middle adults. [ABSTRACT FROM AUTHOR]

Objective: Repetitive Transcranial Magnetic Stimulation (rTMS) has been used in cognition impairment due to various neuropsychiatric disorders. However, its optimum parameters and the neuroimaging mechanism are still of uncertainty. In order to simulate a study setting as close to real world as possible, the present study introduces a new orthogonally-designed protocol, consisting of the rTMS intervention with four key parameters (stimulating site, frequency, intensity and pulse number) and three different levels in each one, and aims to investigate the optimum parameters and the brain activity and connectivity in default mode network (DMN), dorsal attention network (DAN), central executive network (CEN) following rTMS intervention to post-stroke cognition impairment (PSCI). Methods: A single-center, orthogonally-designed, triple-blind randomized controlled trial will be conducted and forty-five PSCI patients will be recruited and randomly assigned to one of nine active rTMS groups based on four rTMS paraments: stimulating site, frequency, intensity and pulse number. Neuropsychological, activities of daily living, quality of life and functional magnetic resonance imaging (fMRI) evaluations were be performed pre-, post- and 3 months after rTMS. Discussion: This study evaluates the optimum parameters of rTMS for patients with post-stroke cognition impairment and explores the alteration of neural function in DMN, DAN, CEN brain network. These results would facilitate the standardized application of rTMS in cognition impairment rehabilitation. [ABSTRACT FROM AUTHOR]

Scholarship indicates that women and gender are underrepresented in Political Science textbooks, particularly those in American Politics. We complement those analyses by focusing on the "companion readers" often paired with textbooks. Readers give students a glimpse at "real political science," showing how the field is studied and what political scientists value. Do the readers convey that "women also know stuff," women are political actors, and gender is a relevant construct? The answer to each of these three questions is a resounding no. Analyzing women and gender representation in readers for three introductory sub-fields (American, Comparative, and Global Politics), we find a strong preference toward scholarship by men. Our results indicate only a small proportion of women authors and an even lower percentage of articles that focus on women. Moreover, the readers have not changed over time resulting in readers that are still "pale, male, and stale." Because readers offer a snapshot of the field, and may be adopted passively in an introductory course, we argue that the absence of women harms students and political science itself. [ABSTRACT FROM AUTHOR]

Autopsies of patients who have died from COVID‐19 have been crucial in delineating patterns of injury associated with SARS‐CoV‐2 infection. Despite their utility, comprehensive autopsy studies are somewhat lacking relative to the global burden of disease, and very few comprehensive studies contextualize the findings to other fatal viral infections. We developed a novel autopsy protocol in order to perform postmortem examinations on victims of COVID‐19 and herein describe detailed clinical information, gross findings, and histologic features observed in the first 16 complete COVID‐19 autopsies. We also critically evaluated the role of ancillary studies used to establish a diagnosis of COVID‐19 at autopsy, including immunohistochemistry (IHC), in situ hybridization (ISH), and electron microscopy (EM). IHC and ISH targeting SARS‐CoV‐2 were comparable in terms of the location and number of infected cells in lung tissue; however, nonspecific staining of bacteria was seen occasionally with IHC. EM was unrevealing in blindly sampled tissues. We then compared the clinical and histologic features present in this series to six archival cases of fatal seasonal influenza and six archival cases of pandemic influenza from the fourth wave of the 'Spanish Flu' in the winter of 1920. In addition to routine histology, the inflammatory infiltrates in the lungs of COVID‐19 and seasonal influenza victims were compared using quantitative IHC. Our results demonstrate that the clinical and histologic features of COVID‐19 are similar to those seen in fatal cases of influenza, and the two diseases tend to overlap histologically. There was no significant difference in the composition of the inflammatory infiltrate in COVID‐19 and influenza at sites of acute lung injury at the time of autopsy. Our study underscores the relatively nonspecific clinical features and pathologic changes shared between severe cases of COVID‐19 and influenza, while also providing important caveats to ancillary methods of viral detection. [ABSTRACT FROM AUTHOR]

Mastectomy breast reconstruction with autologous tissue is challenging. Oncologic and aesthetic goals face previous surgical scars, radiation, chemotherapy, or other comorbidities. We describe a simple approach for autologous mastectomy reconstruction so that breast and plastic and reconstructive surgeons can maximize aesthetic outcomes and minimize wound complications. A retrospective chart review was done on patients who underwent mastectomy and autologous reconstruction. The surgical flight plans were reviewed to delineate an approach, and pre‐ and postoperative photographs were examined to create a step‐by‐step process. The most encountered mastectomy and autologous flap reconstruction scenarios were categorized to create a step‐by‐step process. Successful autologous mastectomy reconstruction to optimize aesthetic outcome and minimize complications requires team communication. Creation of a surgical flight plan using information from the physical examination, MRI and adjunctive imaging, and preoperative photographs is imperative. Thoughtful incision choice and exposure approach are paramount. [ABSTRACT FROM AUTHOR]

Costimulation between T cells and antigen-presenting cells is essential for the regulation of an effective alloimmune response and is not targeted with the conventional immunosuppressive therapy after kidney transplantation. Costimulation blockade therapy with biologicals allows precise targeting of the immune response but without non-immune adverse events. Multiple costimulation blockade approaches have been developed that inhibit the alloimmune response in kidney transplant recipients with varying degrees of success. Belatacept, an immunosuppressive drug that selectively targets the CD28-CD80/CD86 pathway, is the only costimulation blockade therapy that is currently approved for kidney transplant recipients. In the last decade, belatacept therapy has been shown to be a promising therapy in subgroups of kidney transplant recipients; however, the widespread use of belatacept has been tempered by an increased risk of acute kidney transplant rejection. The purpose of this review is to provide an overview of the costimulation blockade therapies that are currently in use or being developed for kidney transplant indications. [ABSTRACT FROM AUTHOR]

Degeneration of synapses in Alzheimer's disease (AD) strongly correlates with cognitive decline, and synaptic pathology contributes to disease pathophysiology. We recently observed that the strongest genetic risk factor for sporadic AD, apolipoprotein E epsilon 4 (APOE4), is associated with exacerbated synapse loss and synaptic accumulation of oligomeric amyloid beta in human AD brain. To begin to understand the molecular cascades involved in synapse loss in AD and how this is mediated by APOE, and to generate a resource of knowledge of changes in the synaptic proteome in AD, we conducted a proteomic screen and systematic in silico analysis of synaptoneurosome preparations from temporal and occipital cortices of human AD and control subjects with known APOE gene status. We examined brain tissue from 33 subjects (7–10 per group). We pooled tissue from all subjects in each group for unbiased proteomic analyses followed by validation with individual case samples. Our analysis identified over 5500 proteins in human synaptoneurosomes and highlighted disease, brain region, and APOE-associated changes in multiple molecular pathways including a decreased abundance in AD of proteins important for synaptic and mitochondrial function and an increased abundance of proteins involved in neuroimmune interactions and intracellular signaling. [ABSTRACT FROM AUTHOR]

Although cognitive and functional impairment are the hallmark features of Alzheimer's disease (AD), neuropsychiatric symptoms associated with AD account for increased rates of disability and profoundly impact the quality of life of both patients and their caregivers. This narrative review of current evidence provides practical guidance in diagnosing and managing depression in patients with AD using pharmacological and nonpharmacological interventions. After apathy, depression is the second most common neuropsychiatric symptom in AD. Diagnosing late-life depression (LLD), particularly in those affected by AD, is complicated because older patients may not meet the criteria for a major depressive disorder. Clinically, late-life depression and dementia can be indistinguishable. Although these two entities are now thought to be related, the pathologic mechanisms remain unclear. Evidence suggests that LLD may be a prodromal symptom of neurodegenerative disease. The various geropsychiatric measures currently used to diagnose, rate the severity of, and monitor the progress of treatment for depression are imperfect. Neuroimaging represents a promising avenue toward understanding the complex pathophysiologic relationships between dementia and LLD, and will support the pursuit of biomarker-driven diagnosis and treatment. Nonpharmacologic interventions to relieve depression in persons with cognitive impairment and dementia include emotion-oriented therapies, behavioral and cognitive-behavioral modification programs, and structured activity programs. Sensory-stimulation therapies and multisensory approaches show some promise for successfully treating depression in patients with dementia, but further rigorous research is needed to establish their validity. Clinical consensus and research appear to support selective serotonin reuptake inhibitors as a first choice for the pharmacological treatment of depression in patients with dementia. However, initial support for these therapies remains variable, and further investigation is needed. Extra care is required in prescribing to this population because of the generally high level of medical and psychiatric comorbidity and the potential difficulty in assessing the cognitively impaired patient's response. [ABSTRACT FROM AUTHOR]