Evaluation and comparison of aging education for undergraduates across multiple fields of study.

The college years represent a key opportunity for broadening the future gerontology workforce by introducing students to the aging content that may influence their career decisions, yet this content is often limited to students with behavioral health and health professions majors. The present study sought to determine the degree to which a Midwestern university's general education course on aging could increase learning, interest, knowledge, and ability to use knowledge for undergraduates across multiple fields of study. Participants included 560 undergraduate students, 48% of which were health professions majors, 28% behavioral health majors, and 23% majors in other fields. While all groups reported significant increases in learning, knowledge, and interest in aging studies, ANOVA found significant differences by students' field of study in reported ability to apply course knowledge in their career or organization. As demand increases for workers versed in the needs of the older adult population, it will be important for educators to incorporate career connections into aging studies coursework and make abundantly clear how students in all fields of study are necessary for the future gerontological workforce.

Omalizumab for the Treatment of Multiple Food Allergies.

BACKGROUND: Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. METHODS: In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension. RESULTS: Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group. CONCLUSIONS: In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.).

Quantification of mast cells in central centrifugal cicatricial alopecia.

Background: Mast cells (MCs) have recently been implicated in lymphocytic scarring alopecias, which may share a common pathogenesis. MCs in central centrifugal cicatricial alopecia (CCCA) have not been studied. Objective: We looked for the presence of MCs in CCCA using 2 different stains to see if their numbers correlated with the number of hair follicles, the degree of inflammation and perifollicular fibrosis, disease duration and severity, and patient symptoms. Methods: We performed a retrospective review of biopsies of patients diagnosed with CCCA, tabulated MC counts and correlated them with histopathologic and clinical findings. Results: MC counts were significantly greater using immunoperoxidase staining with CD117 than Giemsa stain, and more were present when the isthmus level was included with the infundibulum. MC counts with CD117 immunostain significantly correlated with the degree of inflammation. MC counts with both stains were significantly associated with the degree of fibrosis independently and after controlling for other factors. Limitations: The study was limited by insufficient tissue remaining in a small number of the transversely cut blocks. Conclusion: Our findings may have therapeutic implications for CCCA and other types of lymphocytic scarring alopecia.

Rule-Based Text Classification of Dental Diagnosis.

Unstructured medical records boast an abundance of information that could greatly facilitate medical decision-making and improve patient care. With the development of Natural Language Processing (NLP) methodology, the free-text medical data starts to attract more and more research attention. Most existing studies try to leverage the power of such unstructured data using Machine Learning algorithms, which would usually require a relatively large training set, and high computational capacity. However, when faced with a smaller-scale project, opting for an alternative approach may be more effective and practical. This project proposes an efficient and light-weight rule-based approach to categorize dental diagnosis data. It not only fills the void of dental records in the medical free-text processing area, but also demonstrates that with expertly designed research structure and proper implementation, simple method could achieve our study goal very competently.

Cancer History Avoids the Increase of Senescence Markers in Peripheral Cells of Amnestic Mild Cognitive Impaired Patients.

Epidemiological studies show that having a history of cancer protects from the development of Alzheimer's Disease (AD), and vice versa, AD protects from cancer. The mechanism of this mutual protection is unknown. We have reported that the peripheral blood mononuclear cells (PBMC) of amnestic cognitive impairment (aMCI) and Alzheimer's Disease (AD) patients have increased susceptibility to oxidative cell death compared to control subjects, and from the opposite standpoint a cancer history is associated with increased resistance to oxidative stress cell death in PBMCs, even in those subjects who have cancer history and aMCI (Ca + aMCI). Cellular senescence is a regulator of susceptibility to cell death and has been related to the pathophysiology of AD and cancer. Recently, we showed that cellular senescence markers can be tracked in PBMCs of aMCI patients, so we here investigated whether these senescence markers are dependent on having a history of cancer. Senescence-associated ßeta-galactosidase (SA-ß-Gal) activity, G0-G1 phase cell-cycle arrest, p16 and p53 were analyzed by flow cytometry; phosphorylated H2A histone family member X (γH2AX) by immunofluorescence; IL-6 and IL-8 mRNA by qPCR; and plasmatic levels by ELISA. Senescence markers that were elevated in PBMCs of aMCI patients, such as SA-ß-Gal, Go-G1 arrested cells, IL-6 and IL-8 mRNA expression, and IL-8 plasmatic levels, were decreased in PBMCs of Ca + aMCI patients to levels similar to those of controls or of cancer survivors without cognitive impairment, suggesting that cancer in the past leaves a fingerprint that can be peripherally traceable in PBMC samples. These results support the hypothesis that the senescence process might be involved in the inverse association between cancer and AD.

Retail Food Equivalents for Post-Oral Immunotherapy Dosing in the Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy in Food-Allergic Children and Adults (OUtMATCH) Clinical Trial.

BACKGROUND: Patients with food allergy may be advised to introduce specific foods into their diets, both to increase tolerance gradually and as next steps after completing oral immunotherapy or other therapeutic interventions. However, the safe use of retail foods depends on the ability to establish the specific allergen protein content of these foods. OBJECTIVE: To develop a systematic approach to estimate the protein content of peanut, milk, egg, wheat, cashew, hazelnut, and walnut in a variety of retail food equivalents for each allergen and associated patient education materials. METHOD: We created an algorithm that used a multistep process with information from product food labels, nutrient databases, independent weighing and measuring of foods, and information provided by manufacturers, including certificates of analysis, and e-mail communication to estimate the allergen protein content of multiple retail foods for each of seven allergens. Once a variety of retail food equivalents for each allergen and allergen serving size was determined, we developed participant education handouts, which were reviewed by study teams at 10 food allergy centers, the National Institute of Allergy and Infectious Diseases, and the Consortium for Food Allergy Research coordinating center. After 1 year of use, multiple queries were addressed and the retail food equivalents and educational materials were reviewed and edited. RESULTS: We identified a variety of retail food equivalents for seven allergens at six serving sizes, and created 48 unique patient education materials. CONCLUSION: Our results provide extensive guidance on a variety of retail equivalents for seven foods, and a method to estimate retail food protein equivalents systematically with ongoing reassessment.

The impact of a two-year long COVID-19 public health restriction program on mechanical thrombectomy outcomes in a stroke network.

OBJECTIVE: The purpose of this study was to evaluate the impact of COVID-19 pandemic public health restrictions on our drip and ship mechanical thrombectomy program in Santiago Chile. MATERIALS AND METHODS: This was a retrospective analysis of a prospectively collected database comparing two cohorts, one during a two-year period before COVID-19 and the second during the two years of the pandemic at our metropolitan stroke program. RESULTS: A total of 100 patients were included in the pre COVID-19 cohort (cohort 1) and 121 in the COVID-19 cohort (cohort 2). There was a significant difference between cohorts, with older patients, different occlusion sites and higher door to arterial puncture time during the COVID-19 period. A non-significant trend for worse 90-day outcomes and higher mortality was present in cohort 2. There were no statistical differences in safety treatment parameters. CONCLUSIONS: COVID-19 pandemic has had a measurable impact on our mechanical thrombectomy program. Results showed similarities to other reported Latin American series, where less robust health systems could adapt less efficiently compared to developed countries. After two years of public health restrictions, there were changes in the treatment population characteristics, delay in some internal management metrics and a non-significant trend to worse 90-day outcomes and higher mortality.

The Benefits of Community Engaged Research in Creating Place-Based Responses to COVID-19.

Objective: The DSU COVID-19 study aims to understand the response to and impact of COVID-19 in nine underserved communities in Delaware and to inform public health messaging. In this article, we describe our community engaged research approach and discuss the benefits of community engaged research in creating place-based health interventions designed to reduce entrenched health disparities and to respond to emerging or unforeseen health crises. We also highlight the necessity of sustained community engagement in addressing entrenched health disparities most prevalent in underserved communities and in being prepared for emerging and unforeseen health crises. Method: Our study is a longitudinal study comprised of three waves: initial, six months follow-up, and twelve months follow-up. Each wave consists of a structured survey administered on an iPad and a serology test. Through community engaged research techniques, a network of community partners, including trusted community facilities serving as study sites, collaborates on study implementation, data interpretation, and informing public health messaging. Results: The community engaged approach (CEnR) proved effective in recruiting 1,086 study participants from nine underserved communities in Delaware. The research team built a strong, trusting rapport in the communities and served as a resource for accurate information about COVID-19 and vaccinations. Community partners strengthened their research capacity. Collaboratively, researchers and community partners informed public health messaging. Conclusion: The partnerships developed through CEnR allow for place-based tailored health interventions and education. Policy Implications: CEnR continues to be effective in creating mutually beneficial partnerships among researchers, community partners, and community residents. However, CEnR by nature is transactional. Without sustained partnerships with and in underserved communities, we will make little progress in impacting health disparities and will be ill-prepared to respond to emerging or unforeseen health crises. We recommend that population health strategies include sustainable research practice partnerships (RPPs) to increase their impact.

Senescence Markers in Peripheral Blood Mononuclear Cells in Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

Recent studies suggest that cellular senescence plays a role in Alzheimer's Disease (AD) pathogenesis. We hypothesize that cellular senescence markers might be tracked in the peripheral tissues of AD patients. Senescence hallmarks, including altered metabolism, cell-cycle arrest, DNA damage response (DDR) and senescence secretory associated phenotype (SASP), were measured in peripheral blood mononuclear cells (PBMCs) of healthy controls (HC), amnestic mild cognitive impairment (aMCI) and AD patients. Senescence-associated ßeta-galactosidase (SA-ß-Gal) activity, G0-G1 phase cell-cycle arrest, p16 and p53 were analyzed by flow cytometry, while IL-6 and IL-8 mRNA were analyzed by qPCR, and phosphorylated H2A histone family member X (γH2AX) was analyzed by immunofluorescence. Senescent cells in the brain tissue were determined with lipofuscin staining. An increase in the number of senescent cells was observed in the frontal cortex and hippocampus of advanced AD patients. PBMCs of aMCI patients, but not in AD, showed increased SA-ß-Gal compared with HCs. aMCI PBMCs also had increased IL-6 and IL8 mRNA expression and number of cells arrested at G0-G1, which were absent in AD. Instead, AD PBMCs had significantly increased p16 and p53 expression and decreased γH2Ax activity compared with HC. This study reports that several markers of cellular senescence can be measured in PBMCs of aMCI and AD patients.

COVID-19 testing in Delaware's underserved communities: demographic and social determinants of testing inequality.

Background: Health experts believe that frequent COVID-19 testing is one of the most important practices for stopping the spread of the COVID-19 virus. Demographic and social factors might play a role in whether a person gets tested for COVID. This present study aimed to investigate (1) the demographic and social factors affecting a person's likelihood of getting tested for COVID-19, and (2) the demographic and social factors related to a positive serology test (i.e., indicating likely past infection). Methods: Data were extracted from a survey conducted in Delaware's underserved communities. Participants were asked to complete a questionnaire about their COVID-19 testing history, and nurses at the study site collected a serology sample from each participant. Results: Our results indicated that Black or Hispanic individuals living in underserved communities had greater odds of having been tested previously for COVID compared to being non-Hispanic White. In addition, our study found that being female, educated, feeling safe in one's neighborhood, being vaccinated against COVID, and being an essential worker increased one's odds of having been previously tested for COVID-19. Regarding the results of the COVID-19 antibody serology tests, our findings revealed that Hispanic respondents were more likely to have a positive serology test compared to non-Hispanic White respondents, indicating that the Hispanic individuals were more likely to contract the virus. Educated individuals were less likely to have a positive serology test compared to the less-educated. Those who expressed hesitancy about getting vaccinated for COVID-19 and identified themselves as essential workers were more likely to have a positive serology test and to have previously contracted the virus. Conclusions: Identifying key factors associated with COVID-19 testing may help establish novel strategies to increase testing rates among vulnerable population. Public health and policy implications are discussed in the article.

Cancer History Is Associated with Slower Speed of Cognitive Decline in Patients with Amnestic Cognitive Impairment.

BACKGROUND: Several epidemiological studies report a negative association between Cancer and Alzheimer's disease (AD). OBJECTIVE: To characterize the trajectories of memory loss in individuals with early amnestic cognitive impairment with and without history of previous cancer. METHODS: Cognitive deterioration was assessed using the Montreal Cognitive Assessment (MoCA) or MoCA-Memory Index Score (MoCA-MIS) biannually in subjects with early amnestic cognitive impairment followed-up retrospectively from 2007 to 2021. History of Cancer was obtained from clinical records. Simple linear regressions of MoCA-MIS scores were calculated for each subject and analyzed with K-means cluster analysis to identify subgroups with different cognitive decline trajectories. χ2 and t tests were used for descriptive categorical and continuous variables and mixed multiple linear regressions to determine cognitive decline covariates. RESULTS: Analysis of the trajectory of cognitive decline in 141 subjects with early amnestic cognitive impairment identified two subgroups: Fast (n = 60) and Slow (n = 81) progressors. At baseline Fast progressors had better MoCA-MIS (p < 0.001) and functionality (CDR p = 0.02, AD8 p = 0.05), took less anti-dementia medications (p = 0.005), and had higher depression rates (p = 0.02). Interestingly, Fast progressors slowed their speed of memory decline (from 1.6 to 1.1 MoCA-MIS points/year) and global cognitive decline (from 2.0 to 1.4 total MoCA points/year) when Cancer history was present. CONCLUSION: Two trajectories of amnestic cognitive decline were identified, possibly derived from different neurophysiopathologies or clinical stages. This study suggests that a history of previous Cancer slows down amnestic cognitive decline, specifically in a subgroup of subjects with depression at baseline and accelerated deterioration at follow-up.

Interferon Gamma Secretion of Adaptive and Innate Immune Cells as a Parameter to Describe Leukaemia-Derived Dendritic-Cell-Mediated Immune Responses in Acute Myeloid Leukaemia in vitro.

INTRODUCTION: Myeloid leukaemic blasts can be converted into leukaemia-derived dendritic cells (DCleu), characterised by the simultaneous expression of dendritic- and leukaemia-associated antigens, which have the competence to prime and enhance (leukaemia-specific) immune responses with the whole leukaemic antigen repertoire. To display and further specify dendritic cell (DC)- and DCleu-mediated immune responses, we analysed the interferon gamma (IFNy) secretion of innate and adaptive immune cells. METHODS: DC/DCleu were generated from leukaemic whole blood (WB) with (blast)modulatory Kit-I (granulocyte-macrophage colony-stimulating factor [GM-CSF] + Picibanil [OK-432]) and Kit-M (GM-CSF + prostaglandin E1) and were used to stimulate T cell-enriched immunoreactive cells. Initiated anti-leukaemic cytotoxicity was investigated with a cytotoxicity fluorolysis assay. Initiated IFNy secretion of T, NK, CIK, and iNKT cells was investigated with a cytokine secretion assay (CSA). IFNy positivity was additionally evaluated with an intracellular cytokine assay (ICA). Recent activation of leukaemia-specific cells was verified through addition of leukaemia-associated antigens (LAA; WT-1 and Prame). RESULTS: We found Kit-I and Kit-M competent to generate mature DC and DCleu from leukaemic WB without induction of blast proliferation. Stimulation of immunoreactive cells with DC/DCleu regularly resulted in an increased anti-leukaemic cytotoxicity and increased IFNy secretion of T, NK, and CIK cells, pointing to the significant role of DC/DCleu in leukaemia-specific alongside anti-leukaemic reactions. Interestingly, an addition of LAA did not further increase IFNy secretion, suggesting an efficient activation of leukaemia-specific cells. Here, both the CSA and ICA yielded comparable frequencies of IFNy-positive cells. Remarkably, the anti-leukaemic cytotoxicity positively correlated with the IFNy secretion in TCD3+, TCD4+, TCD8+, and NKCD56+ cells. CONCLUSION: Ultimately, the IFNy secretion of innate and adaptive immune cells appeared to be a suitable parameter to assess and monitor the efficacy of in vitro and potentially in vivo acute myeloid leukaemia immunotherapy. The CSA in this regard proved to be a convenient and reproducible technique to detect and phenotypically characterise IFNy-secreting cells. In respect to our studies on DC-based immunomodulation, we were able to display the potential of DC/DCleu to induce or improve leukaemia-specific and anti-leukaemic activity.

COVID-19 Vaccine Hesitancy in Delaware's Underserved Communities.

BACKGROUND AND OBJECTIVE: Vaccine hesitancy may be one of the greatest challenges to conquering the COVID-19 pandemic. Underserved communities across the U.S. have been suffering from the pandemic in unique ways, and vaccine hesitancy may exacerbate or prolong these issues. However, the prevalence of vaccine uptake and hesitancy in these vulnerable populations is unknown. The present study aimed to investigate: (1) prevalence of COVID vaccine uptake and COVID vaccine hesitancy in Delaware's underserved communities; (2) factors (i.e., demographic, socioeconomic characteristics, as well as COVID-related behaviors) associated with vaccine hesitancy; and (3) specific concerns about COVID vaccines. MATERIALS AND METHODS: Data were extracted from a survey conducted in Delaware's underserved communities from March 4, 2021 to May 25, 2021. Logistic regression analyses were used to assess factors associated with vaccine hesitancy. RESULTS: Results from our survey indicated that vaccine uptake is lower in Delaware's underserved communities than Delaware overall and the national average. In addition, a considerable proportion of participants were categorized as vaccine hesitant. We also found that being black increased the likelihood of vaccine hesitancy for the COVID-19 vaccine, which is consistent with prior studies on vaccine hesitancy. Results also indicated that having been tested for COVID in the past decreased the odds of vaccine hesitancy. However, we did not find that demographic or socioeconomic characteristics played a role in vaccine hesitancy in Delaware's underserved communities. CONCLUSION AND RELEVANCE: Our study represents a critial first step in understanding the determinants driving COVID vaccine uptake and hesitancy. Identifying key factors and causes for vaccine hesitancy may help in establishing novel strategies that counteract low vaccination rates in underserved communities.

Diagnostic laparoscopy and oophorectomy for ovarian vein thrombosis in a patient with COVID-19: a surgical case report and literature review.

Ovarian vein thrombosis (OVT) is a rare condition most frequently associated with pelvic inflammatory disease (PID), malignancy or the immediate postpartum period. This case study reports on a 56-year-old woman who developed OVT 11 days after a positive COVID-19 diagnosis. Imaging including abdominal/pelvic computed tomography, transvaginal Doppler ultrasound and transabdominal pelvic ultrasound failed to definitively diagnose the thrombotic etiology of the patient's presentation. Ultimately, laparoscopic visualization and subsequent oophorectomy were necessary for diagnostic and therapeutic purposes. The patient did not have underlying malignancy, recent surgical history, history of PID or any history of previous thromboembolic events. Therefore, this report contributes further evidence to the growing knowledge of systemic manifestations associated with COVID-19 that may require surgical intervention.

Predictors for carotid and femoral artery intima-media thickness in a non-diabetic sleep clinic cohort.

INTRODUCTION: The impact of sleep disordered breathing (SDB) on arterial intima-media thickness (IMT), a surrogate measure for cardiovascular disease, remains uncertain, in part because of the potential for non-SDB vascular risk factor interactions. In the present study, we determined predictors for common carotid (CCA) and femoral (CFA) artery IMT in an adult, sleep clinic cohort where non-SDB vascular risk factors (particularly diabetes) were eliminated or controlled. METHODS: We recruited 296 participants for polysomnography (standard SDB severity metrics) and CCA/CFA ultrasound examinations, followed by a 12 month vascular risk factor minimisation (RFM) and continuous positive pressure (CPAP) intervention for participants with a range of SDB severity (RFM Sub-Group, n = 157; apnea hyponea index [AHI]: 14.7 (7.2-33.2), median [IQR]). Univariable and multivariable linear regression models determined independent predictors for IMT. Linear mixed effects modelling determined independent predictors for IMT change across the intervention study. P<0.05 was considered significant. RESULTS: Age, systolic blood pressure and waist:hip ratio were identified as non-SDB predictive factors for CCA IMT and age, weight and total cholesterol:HDL ratio for CFA IMT. No SDB severity metric emerged as an independent predictor for either CCA or CFA IMT, except in the RFM Sub-Group, where a 2-fold increase in AHI predicted a 2.4% increase in CFA IMT. Across the intervention study, CCA IMT decreased in those who lost weight, but there was no CPAP use interaction. CFA IMT, however, decreased by 12.9% (95%CI 6.8, 18.7%, p = 0.001) in those participants who both lost weight and used CPAP > = 4hours/night. CONCLUSION: We conclude that SDB severity has little impact on CCA IMT values when non-SDB vascular risk factors are minimised or not present. This is the first study, however, to suggest a potential linkage between SDB severity and CFA IMT values. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12611000250932 and ACTRN12620000694910.

Diagnostic Utility of Measuring Cerebral Atrophy in the Behavioral Variant of Frontotemporal Dementia and Association With Clinical Deterioration.

Importance: The presence of atrophy on magnetic resonance imaging can support the diagnosis of the behavioral variant of frontotemporal dementia (bvFTD), but reproducible measurements are lacking. Objective: To assess the diagnostic and prognostic utility of 6 visual atrophy scales (VAS) and the Magnetic Resonance Parkinsonism Index (MRPI). Design, Setting, and Participants: In this diagnostic/prognostic study, data from 235 patients with bvFTD and 225 age- and magnetic resonance imaging-matched control individuals from 3 centers were collected from December 1, 1998, to September 30, 2019. One hundred twenty-one participants with bvFTD had high confidence of frontotemporal lobar degeneration (FTLD) (bvFTD-HC), and 19 had low confidence of FTLD (bvFTD-LC). Blinded clinicians applied 6 previously validated VAS, and the MRPI was calculated with a fully automated approach. Cortical thickness and subcortical volumes were also measured for comparison. Data were analyzed from February 1 to June 30, 2020. Main Outcomes and Measures: The main outcomes of this study were bvFTD-HC or a neuropathological diagnosis of 4-repeat (4R) tauopathy and the clinical deterioration rate (assessed by longitudinal measurements of Clinical Dementia Rating Sum of Boxes). Measures of cerebral atrophy included VAS scores, the bvFTD atrophy score (sum of VAS scores in orbitofrontal, anterior cingulate, anterior temporal, medial temporal lobe, and frontal insula regions), the MRPI, and other computerized quantifications of cortical and subcortical volumes. The areas under the receiver operating characteristic curve (AUROC) were calculated for the differentiation of participants with bvFTD-HC and bvFTD-LC and controls. Linear mixed models were used to evaluate the ability of atrophy measures to estimate longitudinal clinical deterioration. Results: Of the 460 included participants, 296 (64.3%) were men, and the mean (SD) age was 62.6 (11.4) years. The accuracy of the bvFTD atrophy score for the differentiation of bvFTD-HC from controls (AUROC, 0.930; 95% CI, 0.903-0.957) and bvFTD-HC from bvFTD-LC (AUROC, 0.880; 95% CI, 0.787-0.972) was comparable to computerized measures (AUROC, 0.973 [95% CI, 0.954-0.993] and 0.898 [95% CI, 0.834-0.962], respectively). The MRPI was increased in patients with bvFTD and underlying 4R tauopathies compared with other FTLD subtypes (14.1 [2.0] vs 11.2 [2.6] points; P < .001). Higher bvFTD atrophy scores were associated with faster clinical deterioration in bvFTD (1.86-point change in Clinical Dementia Rating Sum of Boxes score per bvFTD atrophy score increase per year; 95% CI, 0.99-2.73; P < .001). Conclusions and Relevance: Based on these study findings, in bvFTD, VAS increased the diagnostic certainty of underlying FTLD, and the MRPI showed potential for the detection of participants with underlying 4R tauopathies. These widely available measures of atrophy can also be useful to estimate longitudinal clinical deterioration.

Acute high folic acid treatment in SH-SY5Y cells with and without MTHFR function leads to gene expression changes in epigenetic modifying enzymes, changes in epigenetic marks, and changes in dendritic spine densities.

Epigenetics are known to be involved in various disorders, including neurobiological disorders like autism. Dietary factors such as folic acid can affect epigenetic marks using methylenetetrahydrofolate reductase (MTHFR) to metabolize folic acid to a one-carbon methyl group. As MTHFR mutations are frequent, it is curious as to whether excess folic acid, with or without functioning MTHFR, could affect gene expression, epigenetics, and neuromorphology. Here, we investigated gene expression and activity of epigenetic modifying enzymes, genome-wide DNA methylation, histone 3 modifications, and dendritic spine densities in SH-SY5Y cells with or without a knockdown of MTHFR and with or without an excess of folic acid. We found alterations to gene expression of epigenetic modifying enzymes, including those associated with disorders like autism. Grouping the epigenetic modifying enzymes by function indicated that gene expression was widely affected for genes that code for enzymes affecting DNA methylation, histone acetylation, histone methylation, histone phosphorylation, and histone ubiquitination when excess folic acid treatment occurred with or without the knockdown of MTHFR. MTHFR was significantly reduced upon excess folic acid treatment whether MTHFR was knocked-down or not. Further, methyl-CpG binding protein 2 expression was significantly decreased with excess folic acid treatment with and without proper MTHFR expression. Global DNA methylation decreased due to the knockdown alone while global hydroxymethylated DNA increased due to the knockdown alone. TET2 expression significantly increased with the MTHFR knockdown alone. Excess folic acid alone induced a decrease in TET3 expression. Excess folic acid induced an increase in dendritic spines without the MTHFR knockdown, but folic acid induced a decrease in dendritic spines when MTHFR was knocked-down. The knockdown alone also increased the dendritic spines significantly. Histone 3 acetylation at lysine 18 was significantly increased when excess folic acid was applied to cells with the MTHFR knockdown, as was histone 3 phosphorylation at serine 10. Broadly, our results indicate that excess folic acid, even with functioning MTHFR, could have detrimental effects on cells.