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Charleen D Adams Beckman Research Institute, Duarte, CA, USACorrespondence: Charleen D AdamsBeckman Research Institute, City of Hope,1500 E. Duarte Road, Duarte, CA, USATel +1 626-841-3931Fax +1 626-841-9204Email chaadams@coh.orgBackground: Alzheimer’s disease is a devastating neurodegenerative disorder. Its worldwide prevalence is over 24 million and is expected to double by 2040. Finding ways to prevent its cognitive decline is urgent.Methods: A two-sample Mendelian randomization study was performed instrumenting glutamine, which is abundant in blood, capable of crossing the blood-brain barrier, and involved in a metabolic cycle with glutamate in the brain.Results: The results reveal a protective effect of circulating glutamine against Alzheimer’s disease (inverse-variance weighted method, odds ratio per 1-standard deviation increase in circulating glutamine = 0.83; 95% CI 0.71, 0.97; P = 0.02).Conclusion: These findings lend credence to the emerging story supporting the modifiability of glutamine/glutamate metabolism for the prevention of cognitive decline. More circulating glutamine might mean that more substrate is available during times of stress, acting as a neuroprotectant. Modifications to exogenous glutamine may be worth exploring in future efforts to prevent and/or treat Alzheimer’s disease.Keywords: Alzheimer’s disease, dementia, metabolism, glutamine, Mendelian randomization, prevention

Navaneeth Narayanan,1,2 Christopher D Adams,1 David W Kubiak,3 Serena Cheng,4 Robyn Stoianovici,5 Leonid Kagan,1,6 Luigi Brunetti1,61Department of Pharmacy Practice, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ, USA; 2Division of Infectious Diseases, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA; 3Department of Pharmacy, Brigham and Women’s Hospital, Boston, MA, USA; 4Department of Pharmacy, VA San Diego Healthcare System, San Diego, CA, USA; 5Department of Pharmacy, University of California, Davis Medical Center, Sacramento, CA, USA; 6Department of Pharmaceutics, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ, USAAbstract: Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major cause of infection in both the hospital and community setting. Obesity is a risk factor for infection, and the prevalence of this disease has reached epidemic proportions worldwide. Treatment of infections in this special population is a challenge given the lack of data on the optimal antibiotic choice and dosing strategies, particularly for treatment of MRSA infections. Obesity is associated with various physiological changes that may lead to altered pharmacokinetic parameters. These changes include altered drug biodistribution, elimination, and absorption. This review provides clinicians with a summary of the literature pertaining to the pharmacokinetic and pharmacodynamic considerations when selecting antibiotic therapy for the treatment of MRSA infections in obese patients.Keywords: obesity, methicillin-resistant Staphylococcus aureus, antibiotics, pharmacokinetics

A model of children's attitudes toward their epilepsy was tested in 173 children (9-14 years) with epilepsy and their parents. Predictor variables tested were child characteristics, family mastery, child worry, child self-efficacy for seizure management, child psychosocial care needs, and seizure variables. Data were analyzed using structural equation modeling, leading to a revised model in which less child worry, greater family mastery, and greater child seizure self-efficacy were directly related to more child positive attitudes. Discussion focuses on potential targets for psychosocial interventions aimed at improving attitudes toward epilepsy. [ABSTRACT FROM AUTHOR]

PURPOSE: To examine the initial psychometric properties for the PARS, a brief interview used to screen for 16 items of adolescent risk and protective factors. METHODS: Participants included 193 adolescents, attending public middle and high schools or a university-based Adolescent Clinic. Participants completed a PARS interview, as well as a battery of questionnaires. Approximately 31% of participants received a second PARS interview from an independent rater to assess inter-rater consistency. RESULTS: Descriptive statistics revealed that participants, on average, were rated as low to moderate risk for health-related difficulties across all PARS items. Descriptive statistics also showed important risk patterns in this sample of adolescents (e.g., 1/5 of sample not exercising at all). Factor analysis yielded a total of five factors (Risk Factors, Protection Factors, Relationships/Mood, Motivation Issues, Weight Issues), accounting for 58% of the variance in PARS item scores. Satisfactory levels of internal consistency and inter-rater agreement for the PARS score were found. Convergent and divergent validity of PARS scores were supported by correlations obtained with similar and dissimilar measures, respectively. A significant age group difference was obtained in the total PARS score, with adolescents aged 17-19 years obtaining higher scores than did adolescents aged 14-16 years. No significant gender differences were found. CONCLUSIONS: Our results support the initial psychometric properties (i.e., reliability, validity) of the PARS as a measure of health risk and protective factors in adolescents. The PARS is a brief, efficient means of obtaining important health risk information from adolescents throughout periodic routine health care visits. [ABSTRACT FROM AUTHOR]

The main purpose of this paper is to review parental factors associated with unintentional burns in early childhood. The problem and characteristics of early childhood burns are discussed. Child injury prevention strategies and models are presented. Parental correlates of pediatric injuries in general and specific to burns are reviewed. In conclusion, the authors recommend greater examination of parental variables potentially amenable to treatment, such as psychological functioning, and improved methodology including the use of prospective analyses, multiple methods and informants, and comparison groups. These efforts should enable greater understanding of parental factors related and causal to early childhood burns and, in turn, guide prevention initiatives. [ABSTRACT FROM AUTHOR]

We investigated youth and parent knowledge of asthma using the Asthma Questionnaire (AQ), a newly developed measure that targets general asthma-related knowledge and knowledge of techniques often utilized to manage asthma symptoms. Participants included 46 youth with asthma and 126 parents of children with asthma. Also participating in the study was a comparison group consisting of 19 youth and 20 parents with no familial history of asthma. Results provided support for internal consistency and discriminant validity. Unlike knowledge measures previously published, the AQ is supported by its multi-informant versions, item format, and satisfactory initial psychometric properties. [ABSTRACT FROM AUTHOR]

Problem-Solving Communication Training (PSCT) is a treatment for parent-adolescent conflict based upon behavioral-family systems theory. Although research has demonstrated that PSCT is an effective and acceptable treatment for alleviating parent-adolescent conflict, researchers note some possible limitations of PSCT. Our primary purpose here is to evaluate both the PSCT literature for parent-adolescent conflict and the literature regarding Behavioral Exchange (BE) treatment. It is conjectured that BE may address some of the limitations of traditional PSCT leading to the argument that Behavioral Marital Therapy (BMT) can serve as a model for combining BE and PSCT procedures to enhance treatment for reducing parent-adolescent conflict. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study investigated the psychometric properties of an adolescent version of the Questionnaire of Eating and Weight Patterns (QEWP-A). METHOD: Male and female adolescents between 10-18 years completed the QEWP-A and measures of depression and eating attitudes. Height and weight were also measured. Parents completed a parental version (QEWP-P) that was referenced to their children. Adolescent and parent responses to the QEWP were independently categorized into no diagnosis (ND), nonclinical binge eating (NCB), and binge eating disorder (BED) groups. RESULTS: Adolescent and parental agreement over the diagnostic categories was as follows: 81.6% for ND, 15.5% for NCB, and 25% for BED with an overall kappa of. 19. Adolescents with BED had significantly higher levels of depression than the other two groups with NCB being higher than ND. For eating attitudes, BED adolescents were more deviant than the other two groups who did not differ from one another. DISCUSSION: The QEWP-A displayed adequate concurrent validity. The low overall agreement between adolescents and their parents was influenced by high and low base rates in the NCB and BED categories, respectively. This lack of agreement is consistent with other behavioral problems such as depression. The data suggest that parental perceptions of eating problems approximate those of their children when no problem is present. However, parents are not as likely to be aware of eating difficulties when they actually exist. Copyright 1999 by John Wiley & Sons, Inc. [ABSTRACT FROM AUTHOR]

A new case of dementia is diagnosed every 3 s. Beyond age, risk prediction of dementia is challenging. There is growing evidence of underlying processes that connect aging across organ systems and may provide insight for early detection, and there is a need to identify early biomarkers at an age when action can be taken to mitigate cognitive decline. We hypothesized that timing of menopause, a marker of ovarian aging, predicts brain age decades later. We used 2086 subjects with multiple "omics" measurements from post-mortem brain samples. Age at menopause (AAM) is positively correlated with cognitive function and negatively correlated with pre-frontal cortex aging acceleration (calculated as estimated biological age from DNA methylation minus chronological age). Genetic correlations showed that at least part of these associations is derived from shared heritability. To dissect the mechanism linking AAM to cognitive decline, we turned to transcriptomic data which confirmed that later AAM was associated with gene expression in pre-frontal cortex consistent with better cognition, and among those who reached menopause naturally, decreased gene expression of pathways implicated in aging. Those with surgical menopause displayed different molecular changes, including perturbed nicotinamide adenine dinucleotide (NAD+) activity, validated by metabolomics. Bile acid metabolism was perturbed in both groups, although different bile acid ratios were associated with AAM in each. Together, our data suggest that AAM is predictive of brain aging and cognition, with potential mediation by the gut, although through different mechanisms depending on the type of menopause., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARB) medications are widely prescribed. We sought to assess how pre-admission use of these medications might impact the response to angiotensin-II treatment during vasodilatory shock., Methods: In a post-hoc subgroup analysis of the randomized, placebo-controlled, Angiotensin Therapy for High Output Shock (ATHOS-3) trial, we compared patients with chronic angiotensin-converting enzyme inhibitor (ACEi) use, and patients with angiotensin receptor blocker (ARB) use, to patients without exposure to either ACEi or ARB. The primary outcome was mean arterial pressure after 1-h of treatment. Additional clinical outcomes included mean arterial pressure and norepinephrine equivalent dose requirements over time, and study-drug dose over time. Biological outcomes included baseline RAS biomarkers (renin, angiotensin-I, angiotensin-II, and angiotensin-I/angiotensin-II ratio), and the change in renin from 0 to 3 h., Results: We included n = 321 patients, of whom, 270 were ACEi and ARB-unexposed, 29 were ACEi-exposed and 22 ARB-exposed. In ACEi/ARB-unexposed patients, angiotensin-treated patients, compared to placebo, had higher hour-1 mean arterial pressure (9.1 mmHg [95% CI 7.6-10.1], p < 0.0001), lower norepinephrine equivalent dose over 48-h (p = 0.0037), and lower study-drug dose over 48-h (p < 0.0001). ACEi-exposed patients treated with angiotensin-II showed similarly higher hour-1 mean arterial pressure compared to ACEi/ARB-unexposed (difference in treatment-effect: - 2.2 mmHg [95% CI - 7.0-2.6], p interaction  = 0.38), but a greater reduction in norepinephrine equivalent dose (p interaction  = 0.0031) and study-drug dose (p interaction  < 0.0001) over 48-h. In contrast, ARB-exposed patients showed an attenuated effect of angiotensin-II on hour-1 mean arterial pressure versus ACEi/ARB-unexposed (difference in treatment-effect: - 6.0 mmHg [95% CI - 11.5 to - 0.6], p interaction  = 0.0299), norepinephrine equivalent dose (p interaction  < 0.0001), and study-drug dose (p interaction  = 0.0008). Baseline renin levels and angiotensin-I/angiotensin-II ratios were highest in ACEi-exposed patients. Finally, angiotensin-II treatment reduced hour-3 renin in ACEi/ARB-unexposed and ACEi-exposed patients but not in ARB-exposed patients., Conclusions: In vasodilatory shock patients, the cardiovascular and biological RAS response to angiotensin-II differed based upon prior exposure to ACEi and ARB medications. ACEi-exposure was associated with increased angiotensin II responsiveness, whereas ARB-exposure was associated with decreased responsiveness. These findings have clinical implications for patient selection and dosage of angiotensin II in vasodilatory shock. Trial Registration ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015)., (© 2024. The Author(s).)

Apolipoprotein B-100 (APOB) is a component of fat- and cholesterol-transporting molecules in the bloodstream. It is the main lipoprotein in low-density lipoprotein cholesterol (LDL) and has been implicated in conditions that end healthspan (the interval between birth and onset of chronic disease). However, APOB's direct relationship with healthspan remains uncertain. With Mendelian randomization, we show that higher levels of APOB and LDL shorten healthspan in humans. Multivariable Mendelian randomization of APOB and LDL on healthspan suggests that the predominant trait accounting for the relationship is APOB. In addition, we provide preliminary evidence that APOB increases risk for Alzheimer's disease, a condition that ends healthspan. If these relationships are causal, they suggest that interventions to improve healthspan in aging populations could include strategies targeting APOB. Ultimately, given that more than 44 million people currently suffer from Alzheimer's disease worldwide, such interventions are needed., (© 2024. The Author(s).)

Huntington's disease (HD) is a neurodegenerative disorder involving psychiatric, cognitive and motor deficits, as well as peripheral symptoms, including gastrointestinal dysfunction. The R6/1 HD mouse model expresses a mutant human huntingtin transgene and has been shown to provide an accurate disease model. Recent evidence of gut microbiome disruption was shown in preclinical and clinical HD. Therefore, we aimed to assess the potential role of gut microbial modulation in the treatment of HD. The R6/1 HD mice and wild-type littermate controls were randomised to receive diets containing different amounts of fibre: high-fibre (10 % fibre), control (5 % fibre), or zero-fibre (0 % fibre), from 6 to 20 weeks of age. We characterized the onset and progression of motor, cognitive and affective deficits, as well as gastrointestinal function and gut morphological changes. Faeces were collected for gut microbiome profiling using 16S rRNA sequencing, at 14 and 20 weeks of age. When compared to the control diet, high-fibre diet improved the performance of HD mice in behavioral tests of cognitive and affective function, as well as the gastrointestinal function of both HD and wild-type mice. While the diets changed the beta diversity of wild-type mice, no statistical significance was observed at 14 or 20 weeks of age within the HD mice. Analysis of Composition of Microbiomes with Bias Correction (ANCOM-BC) models were performed to evaluate microbiota composition, which identified differences, including a decreased relative abundance of the phyla Actinobacteriota, Campylobacterota and Proteobacteria and an increased relative abundance of the families Bacteroidaceae, Oscillospiraceae and Ruminococcaceae in HD mice when compared to wild-type mice after receiving high-fibre diet. PICRUSt2 revealed that high-fibre diet also decreased potentially pathogenic functional pathways in HD. In conclusion, high-fibre intake was effective in enhancing gastrointestinal function, cognition and affective behaviors in HD mice. These findings indicate that dietary fibre interventions may have therapeutic potential in Huntington's disease to delay clinical onset, and have implications for related disorders exhibiting dysfunction of the gut-brain axis., 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 Elsevier Inc. All rights reserved.)