19683 research outputs found
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Sugar-Sweetened Beverages and Adverse Human Health Outcomes: An Umbrella Review of Meta-Analyses of Observational Studies
No full textOur aim was to conduct an umbrella review of evidence from meta-analyses of observational studies investigating the link between sugar-sweetened beverage consumption and human health outcomes. Using predefined evidence classification criteria, we evaluated evidence from 47 meta-analyses encompassing 22,055,269 individuals. Overall, 79% of these analyses indicated direct associations between greater sugar-sweetened beverage consumption and higher risks of adverse health outcomes. Convincing evidence (class I) supported direct associations between sugar-sweetened beverage consumption and risks of depression, cardiovascular disease, nephrolithiasis, type 2 diabetes mellitus, and higher uric acid concentrations. Highly suggestive evidence (class II) supported associations with risks of nonalcoholic fatty liver disease and dental caries. Out of the remaining 40 meta-analyses, 29 were graded as suggestive or weak in the strength of evidence (classes III and IV), and 11 showed no evidence (class V). These findings inform and provide support for population-based and public health strategies aimed at reducing sugary drink consumption for improved health
Nonstandard Errors
No full textIn statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty—nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants
Defining the Traditional Mediterranean Lifestyle: Joint International Consensus Statement
No full textIntroduction: The term “Mediterranean lifestyle” has gained increasing prominence in recent years, yet a specific definition remains elusive. In response, the Mediterranean Lifestyle Medicine Institute Board of Directors convened a multidisciplinary panel comprising international experts and leaders in lifestyle medicine. Their goal was to review existing literature and formulate a consensus definition of the “traditional Mediterranean lifestyle (tMedL),” referring to the historical way of living of the people in the Mediterranean region. This paper presents the agreed consensus statement and a comprehensive holistic definition of the term “traditional Mediterranean lifestyle.”. Methods: Major medical and social sciences electronic databases from inception to February 2023 were searched, employing keywords relevant to the Mediterranean lifestyle and its constituent elements (diet, physical activity, sleep, stress, socialization). Subsequently, definitions for each pillar were created and synthesized to derive a comprehensive definition of the “traditional Mediterranean lifestyle.”. Results: This proposed definition received ratification from the Mediterranean Lifestyle Medicine Institute's expert working group during the First International Mediterranean Lifestyle Medicine Conference held in June 2023 on the island of Leros, Greece. “The traditional Mediterranean lifestyle is characterized by its diverse and adaptable nature. Key facets encompass conviviality, lifelong social connectedness, purposeful living, strong community and familial bonds, harmony with nature and the environment, profound spirituality, adherence to religious practices, preservation of local customs, resilience cultivated through adversity, and a commitment to moderation across all spheres of life.”. Conclusions: This definition comprehensively outlines the primary lifestyle factors ingrained in Mediterranean inhabitants across generations. Its holistic nature furnishes a crucial conceptual framework for directing lifestyle medicine practitioners in assisting patients to mitigate diseases, promote overall well-being, devise research initiatives to investigate the health ramifications of this lifestyle, and inform curriculum development
Discovery of an embryonically derived bipotent population of endothelial-macrophage progenitor cells in postnatal aorta
No full textConverging evidence indicates that extra-embryonic yolk sac is the source of both macrophages and endothelial cells in adult mouse tissues. Prevailing views are that these embryonically derived cells are maintained after birth by proliferative self-renewal in their differentiated states. Here we identify clonogenic endothelial-macrophage (EndoMac) progenitor cells in the adventitia of embryonic and postnatal mouse aorta, that are independent of Flt3-mediated bone marrow hematopoiesis and derive from an early embryonic CX3CR1+ and CSF1R+ source. These bipotent progenitors are proliferative and vasculogenic, contributing to adventitial neovascularization and formation of perfused blood vessels after transfer into ischemic tissue. We establish a regulatory role for angiotensin II, which enhances their clonogenic and differentiation properties and rapidly stimulates their proliferative expansion in vivo. Our findings demonstrate that embryonically derived EndoMac progenitors participate in local vasculogenic responses in the aortic wall by contributing to the expansion of endothelial cells and macrophages postnatally.</p
Long-term mercury accumulation and climate reconstruction of an Australian alpine lake during the late Quaternary
No full textMercury (Hg) is a volatile metal of international concern due to its toxicity, with a large atmospheric emission and transport capacity. The biogeochemical cycle of Hg is sensitive to changes in climate, yet our understanding of the specific impact of climatic factors on the Hg cycle remains limited. Here we use a multi-proxy framework, supported by AMS 14C dating, to interpret climatic events in South-Eastern Australia from ∼18,000 years to 6500 years before present from the sediments of Blue Lake in Australia's alpine region. By combining Hg analysis with Antarctic temperature records and iTRACE climate model outputs, carbon-to‑nitrogen ratios (C:N), macroscopic charcoal, and pollen analysis, we find Hg records within Blue Lake's sediments primarily reflect changes in the catchment as a result of a changing climate. The increase in Hg concentrations began with the onset of the Holocene, following a glacial period during which the region was predominantly rocky, relatively barren, and likely covered by ice and snow. The strong relationship between Hg and organic matter in our record indicates that soil development in the watershed post de-glaciation was a predominant driver of Hg concentration and deposition in Blue Lake. An increase in precipitation and temperature in the Holocene contributed to an increase in nutrients and organic matter, further increasing Hg concentration in Blue Lake. A primary challenge in modern Hg research, particularly in the context of climate change, involves distinguishing changes in Hg levels resulting from human activities from those driven by climatic variations. Our pre-anthropogenic data highlight the long-term interrelationships among climate dynamics, soil processes, and ecological transformations within lake catchments on the geochemical cycle of Hg. These connections should be factored into strategies aimed at mitigating Hg increases in lake sediments resulting from global warming
Radiolabelling and preclinical characterisation of [89Zr]Zr-Df-ATG-101 bispecific to PD-L1/4-1BB
No full textPurpose: ATG-101, a bispecific antibody that simultaneously targets the immune checkpoint PD-L1 and the costimulatory receptor 4-1BB, activates exhausted T cells upon PD-L1 crosslinking. Previous studies demonstrated promising anti-tumour efficacy of ATG-101 in preclinical models. Here, we labelled ATG-101 with 89Zr to confirm its tumour targeting effect and tissue biodistribution in a preclinical model. We also evaluated the use of immuno-PET to study tumour uptake of ATG-101 in vivo. Methods: ATG-101, anti-PD-L1, and an isotype control were conjugated with p-SCN-Deferoxamine (Df). The Df-conjugated antibodies were radiolabelled with 89Zr, and their radiochemical purity, immunoreactivity, and serum stability were assessed. We conducted PET/MRI and biodistribution studies on [89Zr]Zr-Df-ATG-101 in BALB/c nude mice bearing PD-L1-expressing MDA-MB-231 breast cancer xenografts for up to 10 days after intravenous administration of [89Zr]Zr-labelled antibodies. The specificity of [89Zr]Zr-Df-ATG-101 was evaluated through a competition study with unlabelled ATG-101 and anti-PD-L1 antibodies. Results: The Df-conjugation and [89Zr]Zr -radiolabelling did not affect the target binding of ATG-101. Biodistribution and imaging studies demonstrated biological similarity of [89Zr]Zr-Df-ATG-101 and [89Zr]Zr-Df-anti-PD-L1. Tumour uptake of [89Zr]Zr-Df-ATG-101 was clearly visualised using small-animal PET imaging up to 7 days post-injection. Competition studies confirmed the specificity of PD-L1 targeting in vivo. Conclusion: [89Zr]Zr-Df-ATG-101 in vivo distribution is dependent on PD-L1 expression in the MDA-MB-231 xenograft model. Immuno-PET with [89Zr]Zr-Df-ATG-101 provides real-time information about ATG-101 distribution and tumour uptake in vivo. Our data support the use of [89Zr]Zr-Df-ATG-101 to assess tumour and tissue uptake of ATG-101
Peripheral inflammation is associated with brain atrophy and cognitive decline linked to mild cognitive impairment and Alzheimer's disease
No full textInflammation is an important factor in Alzheimer's disease (AD). An NMR measurement in plasma, glycoprotein acetyls (GlycA), captures the overall level of protein production and glycosylation implicated in systemic inflammation. With its additional advantage of reducing biological variability, GlycA might be useful in monitoring the relationship between peripheral inflammation and brain changes relevant to AD. However, the associations between GlycA and these brain changes have not been fully evaluated. Here, we performed Spearman's correlation analyses to evaluate these associations cross-sectionally and determined whether GlycA can inform AD-relevant longitudinal measurements among participants in the Alzheimer's Disease Neuroimaging Initiative (n = 1506), with additional linear models and stratification analyses to evaluate the influences of sex or diagnosis status and confirm findings from Spearman's correlation analyses. We found that GlycA was elevated in AD patients compared to cognitively normal participants. GlycA correlated negatively with multiple concurrent regional brain volumes in females diagnosed with late mild cognitive impairment (LMCI) or AD. Baseline GlycA level was associated with executive function decline at 3-9 year follow-up in participants diagnosed with LMCI at baseline, with similar but not identical trends observed in the future decline of memory and entorhinal cortex volume. Results here indicated that GlycA is an inflammatory biomarker relevant to AD pathogenesis and that the stage of LMCI might be relevant to inflammation-related intervention
Outcomes of the My Therapy self-management program in people admitted for rehabilitation: A stepped wedge cluster randomized clinical trial
No full textBackground: Self-management programs can increase the time spent on prescribed therapeutic exercises and activities in rehabilitation inpatients, which has been associated with better functional outcomes and shorter hospital stays. Objectives: To determine whether implementation of a self-management program (‘My Therapy’) improves functional independence relative to routine care in people admitted for physical rehabilitation. Methods: This stepped wedge, cluster randomized trial was conducted over 54 weeks (9 periods of 6-week duration, April 2021 - April 2022) across 9 clusters (general rehabilitation wards) within 4 hospitals (Victoria, Australia). We included all adults (≥18 years) admitted for rehabilitation to participating wards. The intervention included routine care plus ‘My Therapy’, comprising a sub-set of exercises and activities from supervised sessions which could be performed safely, without supervision or assistance. The primary outcomes were the proportion of participants achieving a minimal clinically important difference (MCID) in the Functional Independence Measure, (FIM™) and change in total FIM™ score from admission to discharge. Results: 2550 participants (62 % women) were recruited (control: n = 1458, intervention: n = 1092), with mean (SD) age 77 (13) years and 37 % orthopedic diagnosis. Under intervention conditions, participants reported a mean (SD) of 29 (21) minutes/day of self-directed therapy, compared to 4 (SD 14) minutes/day, under control conditions. There was no evidence of a difference between control and intervention conditions in the odds of achieving an MCID in FIM™ (adjusted odds ratio 0.93, 95 % CI 0.65 to 1.31), or in the change in FIM™ score (adjusted mean difference: -0.27 units, 95 % CI -2.67 to 2.13). Conclusions: My Therapy was delivered safely to a large, diverse sample of participants admitted for rehabilitation, with an increase in daily rehabilitation dosage. However, given the lack of difference in functional improvement with participation in My Therapy, self-management programs may need to be supplemented with other strategies to improve function in people admitted for rehabilitation. Trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12621000313831), https://www.anzctr.org.au
Addressing the intensity of rehabilitation evidence-practice gap: rapid review, stakeholder perspectives and recommendations for upper limb rehabilitation after acquired brain injury
No full textBackground/Aims: For people living with acquired brain injury from stroke or trauma, clinical practice guidelines recommend high-intensity physical rehabilitation to optimise motor outcomes. There is an acknowledged evidence–practice gap between routine clinical practice and the amount, intensity and type of active upper limb rehabilitation recommended in research-informed guidelines. The aims of this study were to identify methods used to facilitate high doses of upper limb practice in published trials, understand stakeholder perspectives of the barriers and enablers to these methods in hospital settings, and to synthesise findings to form an evidence-based action plan for rehabilitation professionals, service providers and adults living with an acquired brain injury. Methods: A rapid systematic literature review and a series of qualitative interviews with service users and rehabilitation clinicians explored the evidence on intensity and the experience of high intensity rehabilitation following brain injury and stroke. Triangulating this mixed method evidence, recommendations were generated on how to increase upper limb rehabilitation intensity during inpatient therapy. Results: There was consensus in the literature that high-dose motor training improves a person's ability to move their hand and arm after brain injury and stroke. Trials mostly delivered therapy programmes as a replacement to usual care; however, it was unclear how high-intensity therapy was integrated into usual rehabilitation. Methods employed to increase the intensity of upper limb rehabilitation included strategies to optimise engagement (eg encourage independent practice and more practice); clinician-related processes (eg self-auditing, use of groups); environmental factors (eg equipment, dedicated space); and organisational influences (eg professional development, dedicated research positions and mentoring). Qualitative data showed that barriers and facilitators stem from service user factors (eg cognitive ability, advanced age, cultural mores) as well as clinician factors (eg quality of the therapeutic relationship, type and quality of therapist instructions). Organisational factors such as a strong research culture and a commitment to evidence-based practice positively influenced outcomes. Conclusions: There is capacity to increase the intensity of upper limb rehabilitation by optimising organisational support and systems, as well as greater service user engagement in therapy processes. </p
Barriers and enablers to the implementation and sustainability of short-stay arthroplasty programs for elective primary total hip and knee replacement: A systematic review with qualitative evidence synthesis
No full textIntroduction: We aimed to systematically review contemporary evidence on the barriers and enablers to implementing and sustaining short-stay arthroplasty programs for elective primary total hip and knee replacement from the perspectives of patients, health professionals, carers, healthcare administrators, funders and policymakers and to map the findings to the Theoretical Domains Framework (TDF). Methods: Medline, Cumulative Index to Nursing and Allied Health Literature, EMBASE, and the Cochrane Central Register of Controlled Trials were searched (up to 19 August 2023). Primary qualitative or mixed-methods studies reporting on perspectives relating to the review aims that utilised a short-stay programme were eligible for inclusion. Study quality was assessed using the qualitative critical appraisal tool from the Joanna Briggs Institute. Data were analysed inductively. The final themes were mapped to the TDF. The confidence in the findings was assessed using GRADE CERQual. Results: Fifteen studies were included. Twelve barrier themes and twelve enabler themes were identified. Three themes were graded with high confidence, 10 were graded with moderate confidence, three were graded with low confidence, and eight were graded with very low confidence. The most pertinent domains that the themes were mapped to for patients were beliefs about capabilities, reinforcement, and the environmental context and resources. Health professionals identified knowledge, environmental context and resources as important domains. Two domains were identified for carers: (1) social/professional role and identity and (2) memory, attention, and decision processes. Conclusion: We identified key barrier and enabler themes linked to the TDF that can be used to guide implementation initiatives and promote the sustainability of short-stay arthroplasty programs