Evaluation of masks and mask material suitability for bioaerosol capture.

Non-medical masks such as disposable non-medical, commercially produced cloth, and homemade masks are not regulated like surgical masks. Their performance, in terms of filtration efficiency and breathability, is variable and unreliable. This research provides a quantitative evaluation of various non-medical masks, assesses their fabrics' potential for the reduction of transmission of bioaerosols such as the SARS-CoV-2 virus, and compares them to surgical masks and N95 filtering facepiece respirators. Using a testing line with a NaCl challenge aerosol, four types of commercial reusable cloth masks, two types of disposable non-medical masks, three types of surgical or N95 masks, and seven types of commonly available materials were tested individually and in combinations. The testing line and procedure were adapted from the ASTM F2299-03: Standard Test Method for Determining the Initial Efficiency of Materials Used in Medical Face Masks to Penetration by Particulates Using Latex Spheres testing method used for testing surgical masks. Filtration efficiencies at 0.15 µm particle diameter at a face velocity of 25 cm/sec for commercial cloth masks, disposable non-medical masks, surgical masks, commercial mask combinations, and homemade combinations ranged from 16-29%, 39-76%, 91-97%, 51-95%, and 45-94%, respectively. The pressure drop results for the different masks and material combinations were all under 3 mm H2O/cm2 except for one material configuration. This study builds on other research that looks at individual materials and masks by testing combinations alongside the individual masks and materials. With proper layering, household materials can achieve the filtration efficiency and low pressure drop requirements of surgical masks. The filtration capabilities of disposable and cloth mask fabrics vary considerably meaning that they are not a reliable or consistent facemask option, regardless of fit.

Contribution of inflammation markers and quantitative sensory testing (QST) indices of central sensitisation to rheumatoid arthritis pain.

BACKGROUND: Pain, the primary complaint in rheumatoid arthritis (RA), is multifaceted, and may be driven by inflammatory disease activity and central sensitisation. We aimed to ascertain what proportion of RA pain severity is explained by markers of inflammation and quantitative sensory testing (QST) indices of central sensitisation. METHODS: This was a cross-sectional analysis of data from individuals with clinically active RA. Pain severity was assessed using numerical rating scales and inflammation via 28-joint Disease Activity Score (DAS28) and Ultrasound (Greyscale, Power Doppler). Pain sensitivity was assessed by 'static' (tibialis anterior or brachioradialis pressure pain detection threshold-PPT-TA/PPT-BR) and 'dynamic' (temporal summation-TS, conditioned pain modulation-CPM) QST. Bivariate associations used Spearman's correlation coefficients, and multivariable linear regression models determined relative contributions to pain severity. RESULTS: In bivariate analyses of N = 96 (age 65 ± 10y, 77% females) people with RA, pain severity was significantly associated with inflammation indices (r = 0.20 to 0.55), and CPM (r=-0.26). In multivariable models that included TS, CPM, age, sex, and body mass index, inflammation indices remained significantly associated with pain severity. Multivariable models explained 22 to 27% of pain variance. Heterogeneity was apparent for associations with pain between subscores for pain now, strongest or average over the past 4-weeks. CONCLUSIONS: In individuals with clinically active RA, markers of inflammatory disease activity best explain RA pain with only marginal contributions from QST indices of central sensitisation. Although inflammation plays a key role in the experience of RA pain, the greater proportion of pain severity remains unexplained by DAS28 and ultrasound indices of inflammation.

Antipolyphosphate monoclonal antibodies derived from autoimmune mice.

Background: Inorganic polyphosphates (polyPs) are linear chains of phosphates that accelerate blood clotting. Targeting polyP in vivo has been shown to reduce thrombosis. Objectives: To identify and characterize anti-polyP monoclonal antibodies that could be used as analytical tools and as antithrombotic agents. Methods: Hybridomas were prepared from spleen cells from autoimmune NZBWF1/J female mice and screened for anti-polyP antibodies. Antibodies that bound polyP using enzyme-linked immunosorbent assay and pull-down assays were further characterized with plate binding, surface plasmon resonance, and plasma-based clotting assays. Antithrombotic potential was evaluated in a murine ferric chloride-induced carotid artery thrombosis model. Results: Of 4 antibodies that bound polyP in our pull-down assay, 2 (PP2069 and PP2099) were available for further characterization. While analyzing these anti-polyP antibodies, we found secretory leukocyte peptidase inhibitor (SLPI) to be a common contaminant of these antibodies and that SLPI binds polyP. We removed SLPI quantitatively from our purified immunoglobulin G. Both PP2069 and PP2099 immunoglobulin G displayed high affinity for polyP but also bound to other polyanions such as DNA, heparin, and certain other glycosaminoglycans, indicating limited specificity. Both antibodies inhibited polyP-initiated plasma clotting in vitro. When tested in vivo in a mouse thrombosis model, however, neither PP2069 nor PP2099 exhibited a significant antithrombotic effect. Conclusion: Autoimmune mice spontaneously produce antibodies against polyP. The 2 examples of anti-polyP monoclonal antibodies studied here not only bound to polyP with high affinity but also cross-reacted with DNA and heparin. Neither antibody protected against thrombosis in a mouse model, but they might have some utility for in vitro studies of polyP.

Impact of a Cancer Survivorship Continuing Medical Education Course on Learners' Attitudes and Intention to Change Practice.

An innovative, case-based continuing medical education course, Health After Cancer: Cancer Survivorship for Primary Care, was developed to engage clinicians in cancer survivorship care. A post-course survey measured the educational impact of the course on learners' intentions to change practice and changes in attitudes related to interprofessional collaborative practice. Qualitative analysis of free text responses was performed using the immersion-crystallization method. Learners earning continuing education credit (N = 1202) completed the post-course evaluation survey: 17.4% physicians, 8.0% advanced practice providers, 56.7% nurses, 2.2% pharmacists, 15.7% other health professionals. Learners' intended practice changes included improving communication (N = 438), incorporating knowledge into practice (N = 282), prioritizing survivorship clinical care (N = 167), and increasing oncology-primary care collaboration for patients (N = 53). Responses frequently involved more than one theme. Specific actions or knowledge that learners intended to incorporate into practice included improving their assessment of cancer survivor's risk and concerns (N = 128), incorporating knowledge of late effects of cancer treatment into practice (N = 122), educating patients about survivorship topics (N = 117), increasing empathy and understanding of survivors' experiences (N = 94), improving listening skills (N = 70), and dedicating more time to survivorship care (N = 63). Learners' changes in attitudes reflected an increased appreciation for collaboration, especially between oncology and primary care clinicians. A continuing medical education course designed to drive interest in engaging with cancer survivorship topics was effective at shaping learners' attitudes and intent to change practice, and has the potential to improve communication, care coordination, and healthcare experiences of cancer survivors.

Plant but not animal sourced nitrate intake is associated with lower dementia-related mortality in the Australian Diabetes, Obesity, and Lifestyle Study.

Introduction: Dietary nitrate is potentially beneficial for cardiovascular, cerebrovascular, and nervous systems due to its role as a nitric oxide (NO) precursor. Increased nitrate intake improves cardiovascular health and therefore could protect against dementia, given the cardiovascular-dementia link. Objective: To investigate the association between source-dependent nitrate intake and dementia-related mortality. As individuals with diabetes are at higher risk of dementia, a secondary aim was to investigate if the associations between nitrate and dementia varied by diabetes mellitus (DM) and pre-diabetes status. Methods: This study involved 9,149 participants aged ≥25 years from the well-characterised Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study followed over a period of 17 years. Intakes of plant-sourced, vegetable-sourced, naturally occurring animal-sourced nitrate, and processed meat (where nitrate is an allowed additive)-sourced nitrate were assessed from a 74-item food frequency questionnaire completed by participants at baseline and nitrate databases were used to estimate nitrate from these different dietary sources. Associations between source-dependent nitrate intake and dementia-related mortality were assessed using multivariable-adjusted Cox proportional hazards models adjusted for demographics, lifestyle, and dietary factors. Results: Over 17 years of follow-up, 93 (1.0%) dementia-related deaths occurred of 1,237 (13.5%) total deaths. In multivariable-adjusted models, participants with the highest intakes of plant-sourced nitrate (median intake 98 mg/day) had a 57% lower risk of dementia-related mortality [HR (95% CI): 0.43 (0.22, 0.87)] compared to participants with lowest intakes of plant-sourced nitrate (median intake 35 mg/day). A 66% lower risk was also seen for higher intakes of vegetable-sourced nitrate [HR (95% CI): 0.34 (0.17, 0.66)]. No association was observed for animal-sourced nitrate, but the risk was two times higher amongst those who consumed the most processed meat-sourced nitrate intake [HR (95%): 2.10 (1.07, 4.12)]. The highest intake of vegetable-sourced nitrate was associated with a lower risk of dementia-related mortality for those with and without DM and pre-diabetes. Conclusion: Encouraging the intake of nitrate-rich vegetables, such as green leafy vegetables and beetroot, may lower the risk of dementia-related mortality, particularly in individuals with (pre-) diabetes who are at a higher dementia risk.

Publishing priorities in global health: A framework and empirical analysis.

Though vital to health policymaking processes, little is known about the distribution of attention to issues global health journals focus on or their alignment with commitments to health equity. We developed a new framework and methods to help address these analytical gaps. We used content analysis to systematically identify and novel methods to measure attention to themes, subthemes and geographies represented in more than 2,000 research articles published in two of the longest-running multidisciplinary global health journals, Bulletin of the World Health Organization and Health Policy and Planning, between 2004 and 2018. We found four major themes-health systems and conditions received the most attention, followed by population groups and policy dynamics. Finer grained analysis shows that the broad-based journals feature many common themes and some, including subthemes like communicable diseases, financing and children, are heavily favoured over others, such as workforce and noncommunicable diseases. It reveals publishing gaps for some highly marginalised groups and shows attention to health equity fluctuates. The new framework and methods can be used to (1) check the distribution of publishing attention for consistency with global health and specific journal aims and (2) support inquiry into priority setting dynamics in the broader research publishing arena.

Longitudinal associations between exercise and biomarkers in autosomal dominant Alzheimer's disease.

INTRODUCTION: We investigated longitudinal associations between self-reported exercise and Alzheimer's disease (AD)-related biomarkers in individuals with autosomal dominant AD (ADAD) mutations. METHODS: Participants were 308 ADAD mutation carriers aged 39.7 ± 10.8 years from the Dominantly Inherited Alzheimer's Network. Weekly exercise volume was measured via questionnaire and associations with brain volume (magnetic resonance imaging), cerebrospinal fluid biomarkers, and brain amyloid beta (Aß) measured by positron emission tomography were investigated. RESULTS: Greater volume of weekly exercise at baseline was associated with slower accumulation of brain Aß at preclinical disease stages ß = -0.16 [-0.23 to -0.08], and a slower decline in multiple brain regions including hippocampal volume ß = 0.06 [0.03 to 0.08]. DISCUSSION: Exercise is associated with more favorable profiles of AD-related biomarkers in individuals with ADAD mutations. Exercise may have therapeutic potential for delaying the onset of AD; however, randomized controlled trials are vital to determine a causal relationship before a clinical recommendation of exercise is implemented. HIGHLIGHTS: Greater self-reported weekly exercise predicts slower declines in brain volume in autosomal dominant Alzheimer's disease (ADAD). Greater self-reported weekly exercise predicts slower accumulation of brain amyloid beta in ADAD. Associations varied depending on closeness to estimated symptom onset.

Associations Between Chronic Rhinosinusitis and the Development of Non-Cystic Fibrosis Bronchiectasis.

BACKGROUND: Studies have shown an association between chronic rhinosinusitis (CRS) and non-cystic fibrosis (CF) bronchiectasis. OBJECTIVE: We aimed to determine whether CRS increases the risk of developing non-CF bronchiectasis. METHODS: A retrospective analysis was conducted utilizing electronic medical records from an academic center. Patients with CRS without bronchiectasis, with at least 1 chest computed tomography (CT) scan performed after the diagnosis of CRS, were identified between January 2006 and December 2015. Charts were reviewed until May 2022. The control group was age-, sex-, and race-matched, and included patients without CRS, asthma, or chronic obstructive pulmonary disease (COPD) who had at least 1 chest CT scan. Bronchiectasis was identified by chest CT radiology reports. The odds of developing bronchiectasis were analyzed in patients with CRS without asthma or COPD (cohort 1) and patients with CRS with asthma or COPD (cohort 2). RESULTS: The odds of developing bronchiectasis were significantly higher in patients with CRS (139 of 1,594; 8.7%) than in patients in the control group (443 of 7,992; 5.5%; odds ratio OR 1.63; 95% confidence interval [95% CI] 1.34-1.99). Furthermore, the odds of developing bronchiectasis were higher in cohort 1 (63 of 863; 7.3%; OR 1.34; 05% CI 1.02-1.76) and cohort 2 (76/ of 731; 10.4%; OR 1.98; 95% CI 1.53-2.55) versus the control group. After adjusting for confounding diseases, the association was attenuated in cohort 1 (OR 1.22; 95% CI 0.92-1.61) but remained significant in cohort 2 (OR 1.78; 95% CI 1.37-2.31). CONCLUSIONS: The CRS is associated with the future development of non-CF bronchiectasis. Patients with CRS, especially those with asthma or COPD, have a higher likelihood of developing bronchiectasis than patients without CRS.

Rationale and design of the multi organ inflammation with serial testing study: a comprehensive assessment of functional and structural abnormalities in patients with recovered COVID-19.

Introduction: Short-term clinical outcomes from SARS-CoV-2 infection are generally favorable. However, 15-20% of patients report persistent symptoms of at least 12 weeks duration, often referred to as long COVID. Population studies have also demonstrated an increased risk of incident diabetes and cardiovascular disease at 12 months following infection. While imaging studies have identified multi-organ injury patterns in patients with recovered COVID-19, their respective contributions to the disability and morbidity of long COVID is unclear. Methods: A multicenter, observational study of 215 vaccine-naïve patients with clinically recovered COVID-19, studied at 3-6 months following infection, and 133 healthy volunteers without prior SARS-CoV-2 infection. Patients with recovered COVID-19 were screened for long COVID related symptoms and their impact on daily living. Multi-organ, multi-parametric magnetic resonance imaging (MRI) and circulating biomarkers were acquired to document sub-clinical organ pathology. All participants underwent pulmonary function, aerobic endurance (6 min walk test), cognition testing and olfaction assessment. Clinical outcomes were collected up to 1 year from infection. The primary objective of this study is to identify associations between organ injury and disability in patients with long-COVID symptoms in comparison to controls. As a secondary objective, imaging and circulating biomarkers with the potential to exacerbate cardiovascular health were characterized. Discussion: Long-term sequelae of COVID-19 are common and can result in significant disability and cardiometabolic disease. The overall goal of this project is to identify novel targets for the treatment of long COVID including mitigating the risk of incident cardiovascular disease. Study registration: clinicaltrials.gov (MOIST late cross-sectional study; NCT04525404).

Comparative analysis of oxygenator dysfunction in polymethylpentene oxygenators: A pilot study.

INTRODUCTION: Polymethylpentene (PMP) oxygenators serve as the primary oxygenator type utilized for ECMO. With the number of PMP oxygenators available, it has become increasingly important to determine differences among each oxygenator type that can lead to varying metrics of oxygenator dysfunction. METHODS: This study was a retrospective, single-center analysis of adult patients supported on ECMO between December 2020 to December 2021 with varying PMP oxygenators including the Medtronic Nautilus Smart (Minneapolis, MA), the Eurosets AMG PMP (Medolla, Italy) and Getinge Quadrox-iD and the Getinge Cardiohelp HLS Module Advanced System (Gothenberg, Sweden). RESULTS: A total of 19 patients were included in our study. 10 patients (52.6%) were supported with a Medtronic Nautilus Smart oxygenator, 5 patients (26.3%) were supported with an Eurosets AMG PMP Oxygenator, and 4 patients (21.1%) were supported with either a Getinge Quadrox-iD oxygenator or Getinge Cardiohelp HLS system. Patients supported with Eurosets AMG PMP oxygenators experienced higher resistance and lower post-oxygenator PaO2 in comparison to other cohorts (p < .02 and < .002 respectively). There was no difference in measured oxygen transfer between cohorts (p = .667). Two patients, both supported by Eurosets AMG PMP, experienced oxygenator failure (p = .094). CONCLUSION: Radial flow oxygenators are prone to higher resistance and lower post-oxygenator PaO2when compared to transverse flow oxygenators. Future larger multicenter studies are required to fully discern the differences between flow-varying polymethylpentene oxygenators and their appropriate cutoffs for oxygenator dysfunction.

Sleep discrepancy and cognitive function in community-dwelling older adults.

This was the first study to use cluster analysis to characterise sleep discrepancy (the discordance between self-reported and objective sleep) across multiple sleep parameters, in community-dwelling older adults. For sleep efficiency, negative discrepancy (the tendency to self-report worse sleep than objectively-measured) was associated with poorer memory, independent of insomnia severity, depressive symptoms and objective sleep. This suggests a unique role for sleep discrepancy as a possible risk factor for future cognitive decline, and warrants the need for further research.

Comparing priority received by global health issues: a measurement framework applied to tuberculosis, malaria, diarrhoeal diseases and dengue fever.

INTRODUCTION: The relative priority received by issues in global health agendas is subjected to impressionistic claims in the absence of objective methods of assessment of priority. To build an approach for conducting structured assessments of comparative priority health issues receive, we expand the public arenas model (2021) and offer a framework for future assessments of health issue priority in global and national health agendas. METHODS: We aimed to develop a more comprehensive set of measures for conducting multiyear priority comparisons of health issues in six agenda-setting arenas by identifying possible measures and data sources, selecting indicators based on feasibility and comparability of measures and gathering the data on selected indicators. We applied these measures to four communicable diseases-tuberculosis (TB), malaria, diarrhoeal diseases and dengue fever-given their differing impressionistic claims of priority. Where possible, we analysed the annual and/or 5-year trends from 2000 through 2022. RESULTS: We observed that TB and malaria received the highest priority for most periods in the past two decades in most arenas. However, a stagnation in development funding for these two conditions over the last 8-10 years may have fuelled the neglect claims. Despite having a higher disease burden, diarrhoea has been slipping in global priority with reduced spending, fewer clinical trials and stagnating publications. Dengue remains a low-priority condition but has witnessed a sharp rise in attention from the pharmaceutical industry. DISCUSSIONS: We expanded the arenas model by including a transnational arena (international representation) and additional measurements for various arenas. This analysis presents an approach to enable comparative trend analysis of the markers of agenda status over a multiyear period. More such analyses can bring much-desired objectivity in understanding how attention to global or national health issues changes over time in different arenas, potentiating a more equitable allocation of resources.

The Relationship between Diet, Depression, and Alzheimer's Disease: A Narrative Review.

PURPOSE OF REVIEW: This narrative review evaluates the role of diet in the relationship between depression and Alzheimer's disease (AD). RECENT FINDINGS: AD and depression are often comorbid, and depression appears to independently increase the future risk of AD. Evidence suggests diet influences the risk of both conditions directly and indirectly. Diet impacts neurochemical and biological processes that may affect the development and progression of depression and cognitive dysfunction. The dietary components offering the greatest protection against depression and AD are yet to be determined. Current evidence highlights the importance of polyphenolic compounds, folate, B vitamins, and polyunsaturated fatty acids, along with adherence to dietary patterns like the Mediterranean diet, which includes multiple beneficial dietary factors. SUMMARY: The investigation of dietary factors in the prevention of depression and AD is a comparatively young field of research. Comprehensive highly characterised longitudinal datasets and advanced analytical approaches are required to further examine the complex relationship between diet, depression, and AD. There is a critical need for more research in this area to develop effective preventive strategies aimed at maintaining mental and physical health with advancing age.

Analysis of bone structure in PEROMYSCUS: Effects of burrowing behavior.

We compare the effects of burrowing behavior on appendicular bone structure in two Peromyscus (deer mouse) species. P. polionotus creates complex burrows in their territories, while P. eremicus is a non-burrowing nesting mouse. We examined museum specimens' bones of wild-caught mice of the two species and lab-reared P. polionotus not given the opportunity to burrow. Bones were scanned using micro-computed tomography, and cortical and trabecular bone structural properties were quantified. Wild P. polionotus mice had a larger moment of area in the ulnar and tibial cortical bone compared with their lab-reared counterparts, suggesting developmental adaptation to bending resistance. Wild P. polionotus had a larger normalized second moment of area and cross-sectional area in the tibia compared with P. eremicus. Tibial trabecular analysis showed lower trabecular thickness and spacing in wild P. polionotus than in P. eremicus and femoral analysis showed wild P. polionotus had lower thickness than P. eremicus and lower spacing than lab-reared P. polionotus, suggesting adaptation to high loads from digging. Results lay the groundwork for future exploration of the ontogenetic and evolutionary basis of mechanoadaptation in Peromyscus.

How do we know whether treatment has failed? Paradoxical outcomes in counseling with young people.

Background: In both routine practice contexts and research studies, evidence from standardized self-report symptom measures, administered pre- and post-treatment, is predominantly used to determine whether psychotherapy has been successful. Understanding the nature of unsuccessful psychotherapy requires an ability to evaluate the credibility of outcome data generated by such techniques. An important body of research has identified discrepancies between outcomes assessed through symptom measures and those obtained from other sources. However, not enough is known about the extent to which such paradoxical outcomes exist. Objective: This study analyzes the relationship between outcomes, as assessed by a standardized self-report measure, and as assessed by ratings of young people's descriptions of change at post-counseling interviews. Methods: Participants were 50 young people (13-16 years old) who had taken part in a trial of up to 10 weeks of school-based humanistic counseling. Our primary standardized measure was the Young Person's CORE (YP-CORE). To assess young people's experiences of counseling change, three independent raters scrutinized transcripts of post-counseling interviews, and scored levels of helpfulness on a 1 (Not at all helpful) to 10 (Extremely helpful) scale. Inter-rater reliabilities were 0.94 (Cronbach's Alpha) and 0.96 (McDonald's Omega). Sensitivity analyses were conducted to explore relationships between helpfulness ratings and other outcome measures, i.e., satisfaction with counseling (ESQ) and the Goal-Based-Outcome Tool (GBO), and process measures, i.e., the Working Alliance Inventory (WAI-S) and the Barret Lennard Relationship Inventory (BLRI). Results: Multilevel analysis indicated that helpfulness ratings were not significantly associated with changes in YP-CORE scores. Analyzed categorically, 38% of those showing reliable improvement on the standardized measure were below the median for self-described helpfulness, and 47% of those not showing reliable change were at or above the median for self-described helpfulness. Sensitivity analyses demonstrated closer correlations between helpfulness ratings and other outcome measures (ESQ and GBO), and between helpfulness ratings and process measures (WAI-S and BLRI). Discussion: Our results raise questions about reliance on symptom change outcome measures for defining treatment success and failure, given their disparity with clients' own descriptions of the helpfulness of therapy. Implications for practice and research are discussed.

Collecting routine and timely cancer stage at diagnosis by implementing a cancer staging tiered framework: the Western Australian Cancer Registry experience.

BACKGROUND: Current processes collecting cancer stage data in population-based cancer registries (PBCRs) lack standardisation, resulting in difficulty utilising diverse data sources and incomplete, low-quality data. Implementing a cancer staging tiered framework aims to improve stage collection and facilitate inter-PBCR benchmarking. OBJECTIVE: Demonstrate the application of a cancer staging tiered framework in the Western Australian Cancer Staging Project to establish a standardised method for collecting cancer stage at diagnosis data in PBCRs. METHODS: The tiered framework, developed in collaboration with a Project Advisory Group and applied to breast, colorectal, and melanoma cancers, provides business rules - procedures for stage collection. Tier 1 represents the highest staging level, involving complete American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) data collection and other critical staging information. Tier 2 (registry-derived stage) relies on supplementary data, including hospital admission data, to make assumptions based on data availability. Tier 3 (pathology stage) solely uses pathology reports. FINDINGS: The tiered framework promotes flexible utilisation of staging data, recognising various levels of data completeness. Tier 1 is suitable for all purposes, including clinical and epidemiological applications. Tiers 2 and 3 are recommended for epidemiological analysis alone. Lower tiers provide valuable insights into disease patterns, risk factors, and overall disease burden for public health planning and policy decisions. Capture of staging at each tier depends on data availability, with potential shifts to higher tiers as new data sources are acquired. CONCLUSIONS: The tiered framework offers a dynamic approach for PBCRs to record stage at diagnosis, promoting consistency in population-level staging data and enabling practical use for benchmarking across jurisdictions, public health planning, policy development, epidemiological analyses, and assessing cancer outcomes. Evolution with staging classifications and data variable changes will futureproof the tiered framework. Its adaptability fosters continuous refinement of data collection processes and encourages improvements in data quality.

Association of Basal Forebrain Atrophy With Cognitive Decline in Early Alzheimer Disease.

BACKGROUND AND OBJECTIVES: In early Alzheimer disease (AD), ß-amyloid (Aß) deposition is associated with volume loss in the basal forebrain (BF) and cognitive decline. However, the extent to which Aß-related BF atrophy manifests as cognitive decline is not understood. This study sought to characterize the relationship between BF atrophy and the decline in memory and attention in patients with early AD. METHODS: Participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study who completed Aß-PET imaging and repeated MRI and cognitive assessments were included. At baseline, participants were classified based on their clinical dementia stage and Aß status, yielding groups that were cognitively unimpaired (CU) Aß-, CU Aß+, and mild cognitive impairment (MCI) Aß+. Linear mixed-effects models were used to assess changes in volumetric measures of BF subregions and the hippocampus and changes in AIBL memory and attention composite scores for each group compared with CU Aß- participants. Associations between Aß burden, brain atrophy, and cognitive decline were evaluated and explored further using mediation analyses. RESULTS: The cohort included 476 participants (72.6 ± 5.9 years, 55.0% female) with longitudinal data from a median follow-up period of 6.1 years. Compared with the CU Aß- group (n = 308), both CU Aß+ (n = 107) and MCI Aß+ (n = 61) adults showed faster decline in BF and hippocampal volumes and in memory and attention (Cohen d = 0.73-1.74). Rates of atrophy in BF subregions and the hippocampus correlated with cognitive decline, and each individually mediated the impact of Aß burden on memory and attention decline. When all mediators were considered simultaneously, hippocampal atrophy primarily influenced the effect of Aß burden on memory decline (ß [SE] = -0.139 [0.032], proportion mediated [PM] = 28.0%) while the atrophy of the posterior nucleus basalis of Meynert in the BF (ß [SE] = -0.068 [0.029], PM = 13.1%) and hippocampus (ß [SE] = -0.121 [0.033], PM = 23.4%) distinctively influenced Aß-related attention decline. DISCUSSION: These findings highlight the significant role of BF atrophy in the complex pathway linking Aß to cognitive impairment in early stages of AD. Volumetric assessment of BF subregions could be essential in elucidating the relationships between the brain structure and behavior in AD.

Validation of a questionnaire for Central nervous system Aspects of joint Pain: the CAP questionnaire.

BACKGROUND AND AIMS: Neuropathic-like pain, fatigue, cognitive difficulty, catastrophising, anxiety, sleep disturbance, depression, and widespread pain associate with a single factor in people with knee pain. We report the Central Aspects of Pain questionnaire (CAP) to characterise this across painful musculoskeletal conditions. METHODS: CAP was derived from the 8 item CAP-Knee questionnaire, and completed by participants with joint pain in the Investigating Musculoskeletal Health and Wellbeing survey. Subgroups had osteoarthritis, back pain or fibromyalgia. Acceptability was evaluated by feedback and data missingness. Correlation coefficients informed widespread pain scoring threshold in relation to the other items, and evaluated associations with pain. Factor analysis assessed CAP structure. Intraclass Correlation Coefficient (ICC) between paper and electronic administration assessed reliability. Friedman test assessed score stability over 4 years in people reporting knee osteoarthritis. RESULTS: Data were from 3579 participants (58% female, median age; 71 years), including subgroups with osteoarthritis (n = 1158), back pain (n = 1292) or fibromyalgia (n = 177). Across the 3 subgroups, ≥10/26 painful sites on the manikin scored widespread pain. Reliability was high (ICC= 0.89 (95% CI: 0.84-0.92)) and CAP scores fit to 1 and 2 factor model, with a total CAP score that was associated with pain severity and quality (r = 0.50-0.72). In people with knee pain, CAP scores were stable over 4 years at the group level, but displayed significant temporal heterogeneity within individual participants. CONCLUSIONS: Central Aspects of Pain is reliably measured by the CAP questionnaire across a range of painful musculoskeletal conditions, and is a changeable state.

Shifting patterns and competing explanations for infectious disease priority in global health agenda setting arenas.

The highly decentralized nature of global health governance presents significant challenges to conceptualizing and systematically measuring the agenda status of diseases, injuries, risks and other conditions contributing to the collective disease burden. An arenas model for global health agenda setting was recently proposed to help address these challenges. Further developing the model, this study aims to advance more robust inquiry into how and why priority levels may vary among the array of stakeholder arenas in which global health agenda setting occurs. We analyse order and the magnitude of changes in priority for eight infectious diseases in four arenas (international aid, scientific research, pharmaceutical industry and news media) over a period of more than two decades in relation to five propositions from scholarship. The diseases vary on burden and prominence in United Nations Sustainable Development Goal 3 for health and well-being, including four with specific indicators for monitoring and evaluation (HIV/AIDS, tuberculosis, malaria, hepatitis) and four without (dengue, diarrhoeal diseases, measles, meningitis). The order of priority did not consistently align with the disease burden or international development goals in any arena. Additionally, using new methods to measure the scale of annual change in resource allocations that are indicative of priority reveals volatility at the disease level in all arenas amidst broader patterns of stability. Insights around long-term patterns of priority within and among arenas are integral to strengthening analyses that aim to identify pivotal causal mechanisms, to clarify how arenas interact, and to measure the effects they produce.

Single cell RNA sequencing of human eosinophils from nasal polyps reveals eosinophil heterogeneity in chronic rhinosinusitis tissue.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation in the United States, but the actual roles that eosinophils play in CRSwNP remain largely unclear. OBJECTIVE: To reveal the roles and heterogeneity of eosinophils in nasal polyp (NP) tissue, we performed single cell RNA sequencing (scRNA-Seq) analysis of NP tissue. METHODS: Sinonasal tissues (NP and control sinus tissue) and patient matched peripheral blood (PB) samples were obtained from 5 control patients and 5 patients with CRSwNP. Eosinophils were enriched before processing for scRNA-Seq. The gene expression profiles in eosinophils were determined by microwell-based scRNA-Seq technology (BD Rhapsody platform). We predicted the overall function of NP eosinophils by Gene Ontology (geneontology.org) enrichment and pathway analyses and confirmed expression of selected genes by flow cytometry. RESULTS: After filtering out contaminating cells, we detected 5,542 eosinophils from control PB, 3,883 eosinophils from CRSwNP PB, 101 eosinophils from control sinus tissues (not included in further analyses), and 9,727 eosinophils from NPs by scRNA-Seq. We found that 204 genes were downregulated and 354 genes upregulated in NP eosinophils compared to all PB eosinophils (>1.5-fold, Padj < .05). Upregulated genes in NP eosinophils were associated with activation, cytokine-mediated signaling, growth factor activity, NF-κB signaling, and antiapoptotic molecules. NP eosinophils displayed 4 clusters revealing potential heterogeneity of eosinophils in NP tissue. CONCLUSIONS: Elevated eosinophils in NP tissue appear to exist in several subtypes that may play important pathogenic roles in CRSwNP, in part by controlling inflammation and hyperproliferation of other cells.