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Late-onset Alzheimer's disease (AD) can, in part, be considered a metabolic disease. Besides age, female sex and APOE ε4 genotype represent strong risk factors for AD that also give rise to large metabolic differences. We systematically investigated group-specific metabolic alterations by conducting stratified association analyses of 139 serum metabolites in 1,517 individuals from the AD Neuroimaging Initiative with AD biomarkers. We observed substantial sex differences in effects of 15 metabolites with partially overlapping differences for APOE ε4 status groups. Several group-specific metabolic alterations were not observed in unstratified analyses using sex and APOE ε4 as covariates. Combined stratification revealed further subgroup-specific metabolic effects limited to APOE ε4+ females. The observed metabolic alterations suggest that females experience greater impairment of mitochondrial energy production than males. Dissecting metabolic heterogeneity in AD pathogenesis can therefore enable grading the biomedical relevance for specific pathways within specific subgroups, guiding the way to personalized medicine.

BackgroundSkin and soft tissue infections (SSTIs) are a key antimicrobial stewardship target because they are a common infection in hospitalized patients, and non-guideline-concordant antibiotic use is frequent. To inform antimicrobial stewardship interventions, we evaluated the proportion of veterans hospitalized with SSTIs who received guideline-concordant empiric antibiotics or an appropriate total duration of antibiotics.MethodsA retrospective medication use evaluation was performed in 34 Veterans Affairs Medical Centers between 2016 and 2017. Hospitalized patients who received antibiotics for uncomplicated SSTI were included. Exclusion criteria were complicated SSTI, severe immunosuppression, and antibiotics for any non-SSTI indication. Data were collected by manual chart review. The primary outcome was the proportion of patients receiving both guideline-concordant empiric antibiotics and appropriate treatment duration, defined as 5-10 days of antibiotics. Data were analyzed and reported using descriptive statistics.ResultsOf the 3890 patients manually evaluated for inclusion, 1828 patients met inclusion criteria. There were 1299 nonpurulent (71%) and 529 purulent SSTIs (29%). Overall, 250 patients (14%) received guideline-concordant empiric therapy and an appropriate duration. The most common reason for non-guideline-concordance was receipt of antibiotics targeting methicillin-resistant Staphylococcus aureus (MRSA) in 906 patients (70%) with a nonpurulent SSTI. Additionally, 819 patients (45%) received broad-spectrum Gram-negative coverage, and 860 patients (48%) received an antibiotic duration >10 days.ConclusionsWe identified 3 common opportunities to improve antibiotic use for patients hospitalized with uncomplicated SSTIs: use of anti-MRSA antibiotics in patients with nonpurulent SSTIs, use of broad-spectrum Gram-negative antibiotics, and prolonged durations of therapy.

This qualitative narrative correspondence study investigates older adults' experiences of physical activity (PA) during the 2020 COVID-19 pandemic lockdowns in Aotearoa, New Zealand. This paper presents a reflexive thematic analysis of 501 letters received from 568 participants that discussed PA. Participants described PA as bringing joy and rhythm to daily life under stay-at-home measures. The most frequently discussed forms of PA included exercising, gardening, and housework. Four interconnected conceptual themes identified were as follows: (a) renegotiating environmental relationships, (b) social connection, (c) pleasure and PA, and (d) navigating active aging discourses. This paper emphasizes the important environmental and social motivations for becoming and remaining physically active despite restrictions on movement. Older adults' understandings and performance of PA were heavily shaped by active aging discourses. As such, we suggest that initiatives seeking to promote PA should foreground older adults' feelings of connection, productivity, and pleasure and recognize their diversity. This is contrary to current recommendations focused on duration or intensity of older adults' PA. [ABSTRACT FROM AUTHOR]

A challenge facing metabolomics in the analysis of large human cohorts is the cross-laboratory comparability of quantitative metabolomics measurements. In this study, 14 laboratories analyzed various blood specimens using a common experimental protocol provided with the Biocrates AbsoluteIDQ p400HR kit, to quantify up to 408 metabolites. The specimens included human plasma and serum from male and female donors, mouse and rat plasma, as well as NIST SRM 1950 reference plasma. The metabolite classes covered range from polar (e.g., amino acids and biogenic amines) to nonpolar (e.g., diacyl- and triacyl-glycerols), and they span 11 common metabolite classes. The manuscript describes a strict system suitability testing (SST) criteria used to evaluate each laboratory's readiness to perform the assay, and provides the SST Skyline documents for public dissemination. The study found approximately 250 metabolites were routinely quantified in the sample types tested, using Orbitrap instruments. Interlaboratory variance for the NIST SRM-1950 has a median of 10% for amino acids, 24% for biogenic amines, 38% for acylcarnitines, 25% for glycerolipids, 23% for glycerophospholipids, 16% for cholesteryl esters, 15% for sphingolipids, and 9% for hexoses. Comparing to consensus values for NIST SRM-1950, nearly 80% of comparable analytes demonstrated bias of

ObjectiveAnxiety disorders are common, can result in lifelong suffering, and frequently begin before adolescence. Evidence from adults suggests that altered prefrontal-limbic connectivity is a pathophysiological feature of anxiety disorders. More specifically, in adults with anxiety disorders, decreased fractional anisotropy (FA), a measure of white matter integrity, has been observed in the uncinate fasciculus, the major tract that connects limbic and prefrontal regions. Because of the early onset of anxiety disorders and the increased incidence in anxiety disorders in females during their reproductive years, it is important to understand whether the reduction in uncinate fasciculus FA exists in children with anxiety disorders and the extent to which this alteration is sex related. To address these issues, the authors assessed FA in the uncinate fasciculus in unmedicated boys and girls with anxiety disorders.MethodsFA measures were derived from diffusion tensor images that were acquired from 98 unmedicated children (ages 8-12); 52 met criteria for generalized anxiety disorder, separation anxiety disorder, social anxiety disorder, or anxiety disorder not otherwise specified, and 46 were matched control subjects.ResultsTract-based results demonstrated that children with anxiety disorders have significant reductions in uncinate fasciculus FA. A significant sex-by-group interaction and post hoc testing revealed that this effect was evident only in boys. No other main effects or sex-by-group interactions were found for other white matter tracts.ConclusionsThese findings provide evidence of uncinate fasciculus white matter alterations in boys with anxiety disorders. The data demonstrate that anxiety disorder-related alterations in prefrontal-limbic structural connectivity are present early in life, are not related to psychotropic medication exposure, and are sex specific. Building on these findings, future research has the potential to provide insights into the genesis and sexual dimorphism of the pathophysiology that leads to anxiety disorders, as well as to identify sex-specific early-life treatment targets.

IntroductionIncreasing evidence suggests a role for the gut microbiome in central nervous system disorders and a specific role for the gut-brain axis in neurodegeneration. Bile acids (BAs), products of cholesterol metabolism and clearance, are produced in the liver and are further metabolized by gut bacteria. They have major regulatory and signaling functions and seem dysregulated in Alzheimer's disease (AD).MethodsSerum levels of 15 primary and secondary BAs and their conjugated forms were measured in 1464 subjects including 370 cognitively normal older adults, 284 with early mild cognitive impairment, 505 with late mild cognitive impairment, and 305 AD cases enrolled in the AD Neuroimaging Initiative. We assessed associations of BA profiles including selected ratios with diagnosis, cognition, and AD-related genetic variants, adjusting for confounders and multiple testing.ResultsIn AD compared to cognitively normal older adults, we observed significantly lower serum concentrations of a primary BA (cholic acid [CA]) and increased levels of the bacterially produced, secondary BA, deoxycholic acid, and its glycine and taurine conjugated forms. An increased ratio of deoxycholic acid:CA, which reflects 7α-dehydroxylation of CA by gut bacteria, strongly associated with cognitive decline, a finding replicated in serum and brain samples in the Rush Religious Orders and Memory and Aging Project. Several genetic variants in immune response-related genes implicated in AD showed associations with BA profiles.DiscussionWe report for the first time an association between altered BA profile, genetic variants implicated in AD, and cognitive changes in disease using a large multicenter study. These findings warrant further investigation of gut dysbiosis and possible role of gut-liver-brain axis in the pathogenesis of AD.

Pressure injuries, also known as pressure ulcers or 'bed sores', are caused by prolonged pressure on the skin and underlying tissues and are common in healthcare settings. They result from a variety of factors including pressure, moisture and friction, with a higher risk among older adults, post‑surgical patients and those with limited mobility or long‑term conditions. These injuries can extend hospital stays and significantly impact patient recovery and mortality risk. Prevention includes regular repositioning, the use of pressure‑relieving devices, skin care and nutritional support. The National Institute for Health and Care Excellence provides guidelines to mitigate these risks through systematic risk assessments and targeted interventions. Early detection and specialist care by a multidisciplinary team are crucial to improving patient outcomes. Consistent pplication of prevention strategies are needed to reduce incidence, improve patient care and alleviate the economic burden of thesex injuries on the NHS. [ABSTRACT FROM AUTHOR]

Background:Methods:Results:Conclusions:Black birthing people in the United States are disproportionately impacted by maternal mortality and more frequently report physical and verbal mistreatment during intrapartum care. Birth plans for prenatal and postpartum care promote autonomy and agency but have not been used as tools to address disparities in perinatal care.We reviewed the literature on the use of birth plans and communication in the pregnancy care setting. We provide an expert analysis and a recommendation for a comprehensive birth plan that incorporates patient preferences and individualizes patient risks as a communication tool.In this expert opinion we outline how an equity birth plan can address social determinants of health, promote respectful communication and prioritize attention to patient narratives. This instrument can be used to address systemic problems that result in health inequities on a community, provider and institutional level.A birth plan with attention to equity serves as a new paradigm for care which can empower patients and reduce racial inequities in perinatal and postpartum outcomes. [ABSTRACT FROM AUTHOR]

Intergenerational connection (IC) has been posited to mitigate the effects of social isolation and loneliness in older people. Using the film Manawaroa: Still Going Strong, we explored nursing and health sciences’ students’ views about IC, considering themes of loneliness and social connectedness among older people in Aotearoa New Zealand. Thirteen students participated in four online focus groups and data was analyzed using thematic analysis. Four themes included: 1) benefits of IC, 2) barriers to IC, and 3) ways to promote IC and 4) broader discourses affecting IC, which describes underlying discourses around who is considered “old” and who is responsible for IC. Participants concurred IC was beneficial for both older and younger generations. We identified the need for IC education for healthcare professionals to challenge societal prejudices they have absorbed and indicated the importance of promoting IC to also increase social cohesion. [ABSTRACT FROM AUTHOR]

PURPOSE:The aims of this study were (1) to assess the utility of the Quality of Life in Neurological Disorder (Neuro-QoL) questionnaire in patients with carpal tunnel syndrome by comparing the validated patient-reported outcome (PRO) measure Neuro-QoL to the validated Carpal Tunnel Syndrome Assessment Questionnaire (CTSAQ) before and following carpal tunnel release, (2) to compare the measurements of the median nerve cross-sectional area (CSA) using high-resolution ultrasound (HRUS) before and after surgery, and (3) to determine a correlation between HRUS and PRO. METHODS:Individuals diagnosed with carpal tunnel syndrome were evaluated using the CTSAQ, Neuro-QoL, and HRUS before surgery and at 3 months after surgery. RESULTS:Twenty patients completed the study. Overwhelmingly, there was an improvement in symptoms and function assessed by patients on both the Neuro-QoL and the CTSAQ at 3 months after surgery. The Neuro-QoL Physical Function and Upper Extremity scores had strong correlation with the CTSAQ activity score but had low to moderate correlation with the CTSAQ symptoms score, before and after surgery. The HRUS measurements of the median nerve at the carpal tunnel inlet demonstrated a decrease in CSA whereas no noticeable changes were observed at mid tunnel and at the outlet (hook of hamate). The correlations between the ultrasound findings and PRO measures ranged from weak to strong. CONCLUSIONS:Patients had resolution of symptoms and higher physical function following carpal tunnel release measured by both the CTSAQ and the Neuro-QoL scores. The Neuro-QoL self-assessment questionnaire, a measurement of quality of life, correlated well with the CTSAQ. Therefore, it could be used as a self-assessment outcomes tool in patients undergoing carpal tunnel release. At 3 months after surgery, HRUS measurements of the median nerve CSA showed a noticeable decrease of CSA only at the inlet of carpal tunnel. This objective improvement correlated with the improvement in CTSAQ and Neuro-QoL scores. TYPE OF STUDY/LEVEL OF EVIDENCE:Diagnosis II.

As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra- and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium. While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.

IntroductionThe Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, and nonprofit organizations to develop new research directions to transform our understanding of Alzheimer's disease (AD) and propel the development of critically needed therapies. In response to their recommendations, big data at multiple levels are being generated and integrated to study network failures in disease. We used metabolomics as a global biochemical approach to identify peripheral metabolic changes in AD patients and correlate them to cerebrospinal fluid pathology markers, imaging features, and cognitive performance.MethodsFasting serum samples from the Alzheimer's Disease Neuroimaging Initiative (199 control, 356 mild cognitive impairment, and 175 AD participants) were analyzed using the AbsoluteIDQ-p180 kit. Performance was validated in blinded replicates, and values were medication adjusted.ResultsMultivariable-adjusted analyses showed that sphingomyelins and ether-containing phosphatidylcholines were altered in preclinical biomarker-defined AD stages, whereas acylcarnitines and several amines, including the branched-chain amino acid valine and α-aminoadipic acid, changed in symptomatic stages. Several of the analytes showed consistent associations in the Rotterdam, Erasmus Rucphen Family, and Indiana Memory and Aging Studies. Partial correlation networks constructed for Aβ1-42, tau, imaging, and cognitive changes provided initial biochemical insights for disease-related processes. Coexpression networks interconnected key metabolic effectors of disease.DiscussionMetabolomics identified key disease-related metabolic changes and disease-progression-related changes. Defining metabolic changes during AD disease trajectory and its relationship to clinical phenotypes provides a powerful roadmap for drug and biomarker discovery.

Aim: To explore the work of palliative care from the perspectives of district nurses with a focus on the strategies they use to achieve positive outcomes for patients. Design: An exploratory descriptive qualitative study. Methods: A combination of group and individual interviews using semi‐structured interviewing were used to explore district nurses' views of providing palliative care across two large urban community nursing services. Results: Sixteen district nurse participants were interviewed. Three key themes were identified: "Getting what was needed" involved finding solutions, selling a story and establishing relationships. District nurses sought ways to "Stay involved" recognizing the benefit of delaying discharge for some patients. "Completing a nursing task" was a way of managing time constraints and a form of self‐protection from having difficult conversations. Conclusion: This study highlights the importance of understanding the contextual nature of the practice setting in relation to the provision of palliative care. In doing so, it has revealed the strategies district nurses use to overcome the challenges associated with providing palliative care within a generalist workload. Implications for the Profession and/or Patient Care: District nurses experience a tension between managing high patient workloads and remaining patient centred in palliative care. Being task focused is a way of remaining safe while managing a high volume of work and is not always a negative factor in the care they provide. However, focusing on a task while at the same time addressing other unmet needs requires a set of skills that less experienced nurses may not have. Impact: Palliative care education alone will not improve the quality of palliative care provided by generalist community district nurses. The practice context is an important factor to take into consideration when supporting the integration of palliative care in district nursing. No Patient or Public Contribution: No patient or public contribution was made to this study. Reporting Method: We have adhered to the relevant EQUATOR guidelines and used the COREQ reporting method. [ABSTRACT FROM AUTHOR]