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Background and objectivesPrevious studies suggest that lower mitochondrial DNA (mtDNA) copy number (CN) is associated with neurodegenerative diseases. However, whether mtDNA CN in whole blood is related to endophenotypes of Alzheimer disease (AD) and AD-related dementia (AD/ADRD) needs further investigation. We assessed the association of mtDNA CN with cognitive function and MRI measures in community-based samples of middle-aged to older adults.MethodsWe included dementia-free participants from 9 diverse community-based cohorts with whole-genome sequencing in the Trans-Omics for Precision Medicine (TOPMed) program. Circulating mtDNA CN was estimated as twice the ratio of the average coverage of mtDNA to nuclear DNA. Brain MRI markers included total brain, hippocampal, and white matter hyperintensity volumes. General cognitive function was derived from distinct cognitive domains. We performed cohort-specific association analyses of mtDNA CN with AD/ADRD endophenotypes assessed within ±5 years (i.e., cross-sectional analyses) or 5-20 years after blood draw (i.e., prospective analyses) adjusting for potential confounders. We further explored associations stratified by sex and age (

This article draws on a qualitative study of 31 Millennial and Generation Z students to examine the meaning of teacher "caring" in a higher education context. Prior research clearly documents the importance of caring to student engagement, although much of that scholarship focuses on secondary schooling. Research also examines the changing demographics of higher education and new expectations brought to college classrooms by Millennials and others. In this article, we connect the existing research on caring and on generational differences to explore how traditional-aged undergraduates define caring and the degree to which that impacts their willingness to learn. Our findings indicate that students value approachability and relatability as traits in a caring professor; we also find that in-class pedagogical practices can dramatically demonstrate care or lack thereof. Our research suggests that the student success agenda in higher education must take in-class teaching practices seriously in order to impact students' engagement and motivation to learn.

Radiation-induced lymphopenia (RIL) is associated with worse outcomes in patients with multiple solid tumors. Hypofractionated radiation therapy (HFRT) reduces RIL compared with conventionally fractionated radiation therapy (CFRT). However, fractionation effects on immune repertoire (IR) diversity are unknown. RNA-based T- and B-cell receptor sequencing was performed on peripheral lymphocytes collected prospectively before radiation therapy and <4 weeks after the final radiation fraction. Patients received CFRT (≤3 Gy/day × ≥10 days 6 chemotherapy, n = 13) or HFRT (≥5 Gy/day × ≤5 days, n = 10), per institutional standards of care. Immune repertoire diversity parameters analyzed were number of unique CDR3 receptors (uCDR3), Shannon entropy, and sample clonality (percentage of all receptors represented by the top 10 clones). RIL was severe with concurrent chemotherapy (median %D ALC -58.8%, –12.5%, and –28.6% in patients treated with CFRT and chemo, CFRT alone, and HFRT, respectively). CFRT and concurrent chemotherapy was associated with more severe diversity restriction in all examined parameters than either HFRT or CFRT alone. Increased immune repertoire diversity despite decreased ALC was more common in patients treated with HFRT than CFRT and significantly less common in patients treated with concurrent chemotherapy (P < 0.001). Radiation-induced changes in immune repertoire diversity are variably reflected in the peripheral ALC. Both HFRT and CFRT caused RIL, but HFRT was associated with improved immune repertoire diversity despite RIL. The addition of chemotherapy may potentiate radiation-induced restriction in immune repertoire diversity. As immune repertoire diversity is associated with response to immunotherapy, these findings may have implications for radiation therapy/chemotherapy/immunotherapy combinations. Further studies are required to understand the relationship between radiation, circulating lymphocyte populations, immune repertoire diversity and response to treatment. [ABSTRACT FROM AUTHOR]

Background and Objectives Physical capability, social support, loneliness, depression, and anxiety predict life satisfaction in older adults. Currently, no systematic review and meta-analysis have been conducted to investigate the strength of these associations globally. Therefore, this study quantified the strength of these associations. Research Design and Methods A systematic literature search was conducted using MEDLINE, EMBASE, APA PsycINFO, Web of Science, and Scopus. We included observational studies assessing the association between physical capability, social support, loneliness, depression, and anxiety with life satisfaction in adults aged 65+. Results In total, 10,552 articles were identified, of which 78 studies in 164,478 participants were included in the systematic review and 57 were included in the meta-analysis. Greater life satisfaction was significantly associated with greater physical capabilities (odds ratio [OR] = 2.64; 95% confidence interval [CI]: 2.01–3.45; p  < .001, k  = 35, n  = 33,732), higher social support (OR = 3.27; 95% CI: 2.59–4.13, k  = 20 studies, n  = 13,228), reduced loneliness (OR = 3.30; 95% CI: 2.53–4.30, k  = 11, n  = 33,638), depression (OR = 4.76; 95% CI: 3.10–7.32, k  = 24, n  = 64,097), and anxiety (OR = 5.10; 95% CI: 2.21–11.78, k  = 5, n  = 43,368). The strength of associations did not vary between Western and Eastern countries, year of publication, or quality. Gender was a moderator: Loneliness was more strongly associated with life satisfaction in females. Age was also a moderator; the association between social support and life satisfaction weakened with increasing age. Discussion and Implications Improving the physical capabilities of older individuals, fostering social support, and alleviating feelings of loneliness, depression, and anxiety may help build life satisfaction in older individuals, which policy-makers and healthcare professionals should prioritize when implementing strategies. [ABSTRACT FROM AUTHOR]

The word naynaa which occurs in the Jamul dialect of Diegueno has four functions: it is used as an emphatic, as an emphatic marker of coreference between a possessor and the subject of its clause, in the reflexive construction, and as an emphatic same subject marking device in complex sentences. This paper describes the uses of naynaa in detail.

ObjectiveTo develop recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP).MethodsWe conducted a systematic review to synthesize the evidence for the benefits and harms of GIOP prevention and treatment options. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence. We used a group consensus process to determine the final recommendations and grade their strength. The guideline addresses initial assessment and reassessment in patients beginning or continuing long-term (≥3 months) glucocorticoid (GC) treatment, as well as the relative benefits and harms of lifestyle modification and of calcium, vitamin D, bisphosphonate, raloxifene, teriparatide, and denosumab treatment in the general adult population receiving long-term GC treatment, as well as in special populations of long-term GC users.ResultsBecause of limited evidence regarding the benefits and harms of interventions in GC users, most recommendations in this guideline are conditional (uncertain balance between benefits and harms). Recommendations include treating only with calcium and vitamin D in adults at low fracture risk, treating with calcium and vitamin D plus an additional osteoporosis medication (oral bisphosphonate preferred) in adults at moderate-to-high fracture risk, continuing calcium plus vitamin D but switching from an oral bisphosphonate to another antifracture medication in adults in whom oral bisphosphonate treatment is not appropriate, and continuing oral bisphosphonate treatment or switching to another antifracture medication in adults who complete a planned oral bisphosphonate regimen but continue to receive GC treatment. Recommendations for special populations, including children, people with organ transplants, women of childbearing potential, and people receiving very high-dose GC treatment, are also made.ConclusionThis guideline provides direction for clinicians and patients making treatment decisions. Clinicians and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Key Points: Question: Is medication abortion provided using no-test eligibility screening and mailing of medications as effective as in-person care with ultrasonography and safe overall? Findings: This prospective, observational study found that medication abortion obtained following no-test telehealth screening and mailing of medications was associated with similar rates of complete abortion compared with in-person care with ultrasonography (94.4% vs 93.3%, respectively) and met the 5% noninferiority margin, with a low prevalence of adverse events. Meaning: The findings suggest that models of medication abortion care that rely on no-test eligibility assessment and mailing medications to patients are an option for individuals considering medication abortion. Importance: In the US, access to medication abortion using history-based (no-test) eligibility assessment, including through telehealth and mailing of mifepristone, has grown rapidly. Additional evidence on the effectiveness and safety of these models is needed. Objective: To evaluate whether medication abortion with no-test eligibility assessment and mailing of medications is as effective as in-person care with ultrasonography and safe overall. Design, Setting, and Participants: Prospective, observational study with noninferiority analysis. Sites included 4 abortion-providing organizations in Colorado, Illinois, Maryland, Minnesota, Virginia, and Washington from May 2021 to March 2023. Eligible patients were seeking medication abortion up to and including 70 days' gestation, spoke English or Spanish, and were aged 15 years or older. Exposure: Study groups reflected the model of care selected by the patient and clinicians and included: (1) no-test (telehealth) eligibility assessment and mailing of medications (no-test + mail) (n = 228); (2) no-test eligibility assessment and pickup of medications (no-test + pickup) (n = 119); or (3) in-person with ultrasonography (n = 238). Main Outcomes and Measures: Effectiveness, defined as a complete abortion without the need for repeating the mifepristone and misoprostol regimen or a follow-up procedure, and safety, defined as an abortion-related serious adverse event, including overnight hospital admission, surgery, or blood transfusion. Outcomes were derived from patient surveys and medical records. Primary analysis focused on the comparison of the no-test + mail group with the in-person with ultrasonography group. Results: The mean age of the participants (N = 585) was 27.3 years; most identified as non-Hispanic White (48.6%) or non-Hispanic Black (28.1%). Median (IQR) gestational duration was 45 days (39-53) and comparable between study groups (P =.30). Outcome data were available for 91.8% of participants. Overall effectiveness was 94.4% (95% CI, 90.7%-99.2%) in the no-test + mail group and 93.3% (95% CI, 88.3%-98.2%) in the in-person with ultrasonography group in adjusted models (adjusted risk difference, 1.2 [95% CI, −4.1 to 6.4]), meeting the prespecified 5% noninferiority margin. Serious adverse events included overnight hospitalization (n = 4), blood transfusion (n = 2), and emergency surgery (n = 1) and were reported by 1.1% (95% CI, 0.4%-2.4%) of participants, with 3 in the no-test + mail group, 3 in the in-person with ultrasonography group, and none in the no-test + pickup group. Conclusions and Relevance: This prospective, observational study found that medication abortion obtained following no-test telehealth screening and mailing of medications was associated with similar rates of complete abortion compared with in-person care with ultrasonography and met prespecified criteria for noninferiority, with a low prevalence of adverse events. This prospective, observational study investigates the efficacy and safety of medication abortion provided using no-test telehealth eligibility screening and mailing of medications compared with in-person care with ultrasonography in the US. [ABSTRACT FROM AUTHOR]

In the United States, melanoma skin cancer deaths are expected to rise by 4.4% in 2023, reaching 7990. Early detection through visual screening can save lives, but the US Preventive Services Task Force cites insufficient evidence to recommend universal skin screening for all adults. For this reason, the risk for melanoma may be overlooked outside of dermatology settings, leading to delayed diagnoses and poor survival rates. Our project aimed to address this issue by increasing the identification of at-risk individuals visiting a medical aesthetic practice in the Midwest. The literature regarding melanoma risk stratification outside of dermatology settings is deficient. A search yielding 336 articles produced 8 articles for review. Five suggested melanoma risk screenings in general practice are feasible and/or can lead to early detection. Using the Plan-Do-Study-Act model, we executed our project from February through April 2023. Patients visiting the medical aesthetic practice completed a Self-Assessment Melanoma Risk Score questionnaire. We assessed the completed questionnaires and offered visual cancer screenings or dermatology referrals to patients identified as at-risk. A total of 211 patients participated, and 26% (n = 55) were identified as at-risk. This intervention improved the quality of care by identifying patients at risk for melanoma. Future steps include adapting the Self-Assessment of Melanoma Risk Score questionnaire to a new electronic medical record system, incorporating the questionnaire as part of the initial intake and annual patient documentation, and improving patient education and follow-up. [ABSTRACT FROM AUTHOR]

Wilson disease (WD), a genetic disorder affecting copper transport, is characterized by hepatic and neurological manifestations with variable and often unpredictable presentation. Global DNA methylation in liver was previously modified by dietary choline in tx-j mice, a spontaneous mutant model of WD. We therefore hypothesized that the WD phenotype and hepatic gene expression of tx-j offspring could be modified by maternal methyl supplementation during pregnancy. In an initial experiment, female tx-j mice or wild type mice were fed control or choline-supplemented diets 2 weeks prior to mating through embryonic day 17. Transcriptomic analysis (RNA-seq) on embryonic livers revealed tx-j-specific differences in genes related to oxidative phosphorylation, mitochondrial dysfunction, and the neurological disorders Huntington's disease and Alzheimer disease. Maternal choline supplementation restored the transcript levels of a subset of genes to wild type levels. In a separate experiment, a group of tx-j offspring continued to receive choline-supplemented or control diets, with or without the copper chelator penicillamine (PCA) for 12 weeks until 24 weeks of age. Combined choline supplementation and PCA treatment of 24-week-old tx-j mice was associated with increased liver transcript levels of methionine metabolism and oxidative phosphorylation-related genes. Sex differences in gene expression within each treatment group were also observed. These results demonstrate that the transcriptional changes in oxidative phosphorylation and methionine metabolism genes in WD that originate during fetal life are, in part, prevented by prenatal maternal choline supplementation, a finding with potential relevance to preventive treatments of WD.

ObjectiveTo highlight the opportunities and challenges of developing and implementing performance outcome measures in rheumatology for accountability purposes.MethodsWe constructed a hypothetical performance outcome measure to demonstrate the benefits and challenges of designing quality measures that assess patient outcomes. We defined the data source, measure cohort, reporting period, period at risk, measure outcome, outcome attribution, risk adjustment, reliability and validity, and reporting approach. We discussed outcome measure challenges specific to rheumatology and to fields where patients have predominantly chronic, complex, ambulatory care-sensitive conditions.ResultsOur hypothetical outcome measure was a measure of rheumatoid arthritis disease activity intended for evaluating Accountable Care Organization performance. We summarized the components, benefits, challenges, and tradeoffs between feasibility and usability. We highlighted how different measure applications, such as for rapid cycle quality improvement efforts versus pay for performance programs, require different approaches to measure development and testing. We provided a summary table of key take-home points for clinicians and policymakers.ConclusionPerformance outcome measures are coming to rheumatology, and the most effective and meaningful measures can only be created through the close collaboration of patients, providers, measure developers, and policymakers. This study provides an overview of key issues and is intended to stimulate a productive dialogue between patients, practitioners, insurers, and government agencies regarding optimal performance outcome measure development.

ObjectiveTo provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA).MethodsA core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946-2014), PubMed (1966-2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework.ResultsIn patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS.ConclusionThese recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas.

To evaluate nitrogen (N) saturation in xeric environments, we measured hydrologic N losses, soil N pools, and microbial processes, and developed an N-budget for a chaparral catchment (Sierra Nevada, California) exposed to atmospheric N inputs of approximately 8.5 kg N ha⁻¹ y⁻¹. Dual-isotopic techniques were used to trace the sources and processes controlling nitrate (NO₃ ⁻) losses. The majority of N inputs occurred as ammonium. At the onset of the wet season (November to April), we observed elevated streamwater NO₃ ⁻ concentrations (up to 520 µmol l⁻¹), concomitant with the period of highest gaseous N-loss (up to 500 ng N m⁻² s⁻¹) and suggesting N-saturation. Stream NO₃ ⁻ δ¹⁵N and δ¹⁸O and soil N measurements indicate that nitrification controlled NO₃ ⁻ losses and that less than 1% of the loss was of atmospheric origin. During the late wet season, stream NO₃ ⁻ concentrations decreased (to

The Mushroom Council convened the Mushrooms and Health Summit in Washington, DC, on 9-10 September 2013. The proceedings are synthesized in this article. Although mushrooms have long been regarded as health-promoting foods, research specific to their role in a healthful diet and in health promotion has advanced in the past decade. The earliest mushroom cultivation was documented in China, which remains among the top global mushroom producers, along with the United States, Italy, The Netherlands, and Poland. Although considered a vegetable in dietary advice, mushrooms are fungi, set apart by vitamin B-12 in very low quantity but in the same form found in meat, ergosterol converted with UV light to vitamin D2, and conjugated linoleic acid. Mushrooms are a rare source of ergothioneine as well as selenium, fiber, and several other vitamins and minerals. Some preclinical and clinical studies suggest impacts of mushrooms on cognition, weight management, oral health, and cancer risk. Preliminary evidence suggests that mushrooms may support healthy immune and inflammatory responses through interaction with the gut microbiota, enhancing development of adaptive immunity, and improved immune cell functionality. In addition to imparting direct nutritional and health benefits, analysis of U.S. food intake survey data reveals that mushrooms are associated with higher dietary quality. Also, early sensory research suggests that mushrooms blended with meats and lower sodium dishes are well liked and may help to reduce intakes of red meat and salt without compromising taste. As research progresses on the specific health effects of mushrooms, there is a need for effective communication efforts to leverage mushrooms to improve overall dietary quality.