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Depression is an important, potentially modifiable dementia risk factor. However, it is not known whether effective treatment of depression through psychological therapies is associated with reduced dementia incidence. The aim of this study was to investigate associations between reduction in depressive symptoms following psychological therapy and the subsequent incidence of dementia.
National psychological therapy data were linked with hospital records of dementia diagnosis for 119808 people aged 65+. Participants received a course of psychological therapy treatment in Improving Access to Psychological Therapies (IAPT) services between 2012 and 2019. Cox proportional hazards models were run to test associations between improvement in depression following psychological therapy and incidence of dementia diagnosis up to eight years later.
Improvements in depression following treatment were associated with reduced rates of dementia diagnosis up to 8 years later (HR = 0.88, 95% CI 0.83–0.94), after adjustment for key covariates. Strongest effects were observed for vascular dementia (HR = 0.86, 95% CI 0.77–0.97) compared with Alzheimer's disease (HR = 0.91, 95% CI 0.83–1.00).
Reliable improvement in depression across psychological therapy was associated with reduced incidence of future dementia. Results are consistent with at least two possibilities. Firstly, psychological interventions to improve symptoms of depression may have the potential to contribute to dementia risk reduction efforts. Secondly, psychological therapies may be less effective in people with underlying dementia pathology or they may be more likely to drop out of therapy (reverse causality). Tackling the under-representation of older people in psychological therapies and optimizing therapy outcomes is an important goal for future research.
During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) intracellular life-cycle, two large polyproteins, pp1a and pp1ab, are produced. Processing of these by viral cysteine proteases, the papain-like protease (PLpro) and the chymotrypsin-like 3C-like protease (3CL-pro) release non-structural proteins necessary for the establishment of the viral replication and transcription complex (RTC), crucial for viral replication. Hence, these proteases are considered prime targets against which anti-coronavirus disease 2019 (COVID-19) drugs could be developed. Here, we describe the expression of a highly soluble and functionally active recombinant 3CL-pro using Escherichia coli BL21 cells. We show that the enzyme functions in a dimeric form and exhibits an unexpected inhibitory profile because its activity is potently blocked by serine rather than cysteine protease inhibitors. In addition, we assessed the ability of our 3CL-pro to function as a carrier for the receptor binding domain (RBD) of the Spike protein. The co-expressed chimeric protein, 3CLpro-RBD, did not exhibit 3CL-pro activity, but its enhanced solubility made purification easier and improved RBD antigenicity when tested against serum from vaccinated individuals in ELISAs. Chimeric proteins containing the 3CL-pro could represent an innovative approach to developing new COVID-19 vaccines.
American Indian and Alaska Native peoples (AI/AN) have a disproportionately high rate of obesity, but little is known about the social determinants of obesity among older AI/AN. Thus, our study assessed social determinants of obesity in AI/AN aged ≥ 50 years.
We conducted a cross-sectional analysis using multivariate generalised linear mixed models to identify social determinants associated with the risk of being classified as obese (BMI ≥ 30·0 kg/m2). Analyses were conducted for the total study population and stratified by median county poverty level.
Indian Health Service (IHS) data for AI/AN who used IHS services in FY2013.
Totally, 27 696 AI/AN aged ≥ 50 years without diabetes.
Mean BMI was 29·8 ± 6·6 with 43 % classified as obese. Women were more likely to be obese than men, and younger ages were associated with higher obesity risk. While having Medicaid coverage was associated with lower odds of obesity, private health insurance was associated with higher odds. Living in areas with lower rates of educational attainment and longer drive times to primary care services were associated with higher odds of obesity. Those who lived in a county where a larger percentage of people had low access to a grocery store were significantly less likely to be obese.
Our findings contribute to the understanding of social determinants of obesity among older AI/AN and highlight the need to investigate AI/AN obesity, including longitudinal studies with a life course perspective to further examine social determinants of obesity in older AI/AN.
The novel coronavirus, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is the causative agent of the 2020 worldwide coronavirus pandemic. Antibody testing is useful for diagnosing historic infections of a disease in a population. These tests are also a helpful epidemiological tool for predicting how the virus spreads in a community, relating antibody levels to immunity and for assessing herd immunity. In the present study, SARS-CoV-2 viral proteins were recombinantly produced and used to analyse serum from individuals previously exposed, or not, to SARS-CoV-2. The nucleocapsid (Npro) and spike subunit 2 (S2Frag) proteins were identified as highly immunogenic, although responses to the former were generally greater. These two proteins were used to develop two quantitative enzyme-linked immunosorbent assays (ELISAs) that when used in combination resulted in a highly reliable diagnostic test. Npro and S2Frag-ELISAs could detect at least 10% more true positive coronavirus disease-2019 (COVID-19) cases than the commercially available ARCHITECT test (Abbott). Moreover, our quantitative ELISAs also show that specific antibodies to SARS-CoV-2 proteins tend to wane rapidly even in patients who had developed severe disease. As antibody tests complement COVID-19 diagnosis and determine population-level surveillance during this pandemic, the alternative diagnostic we present in this study could play a role in controlling the spread of the virus.
Affective symptoms are associated with cognition in mid-life and later life. However, the role of cardiometabolic risk in this association has not been previously examined.
To investigate how cardiometabolic risk contributes to associations between affective symptoms and mid-life cognition.
Data were used from the National Child Development Study (NCDS), a sample of people born in Britain during one week in 1958. Measures of immediate and delayed memory, verbal fluency and information processing speed and accuracy were available at age 50. Affective symptoms were assessed at ages 23, 33 and 42 years and a measure of accumulation was derived. A cardiometabolic risk score was calculated from nine cardiometabolic biomarkers at age 44. Path models were run to test these associations, adjusting for sex, education, socioeconomic position and affective symptoms at age 50.
After accounting for missing data using multiple imputation, path models indicated significant indirect associations between affective symptoms and mid-life immediate memory (β = −0.002, s.e. = 0.001, P = 0.009), delayed memory (β = −0.002, s.e. = 0.001, P = 0.02) and verbal fluency (β = −0.002, s.e. = 0.001, P = 0.045) through cardiometabolic risk.
These findings suggest that cardiometabolic risk may play an important role in the association between affective symptoms and cognitive function (memory and verbal fluency). Results contribute to understanding of biological mechanisms underlying associations between affective symptoms and cognitive ageing, which can have implications for early detection of, and intervention for, those at risk of poorer cognitive outcomes.
Affective disorders are associated with poorer cognition in older adults; however, whether this association can already be observed in mid-life remains unclear.
To investigate the effects of affective symptoms over a period of 30 years on mid-life cognitive function. First, we explored whether timing (sensitive period) or persistence (accumulation) of affective symptoms predicted cognitive function. Second, we tested how different longitudinal trajectories of affective symptoms were associated with cognitive function.
The study used data from the National Child Development Study. Memory, verbal fluency, information processing speed and accuracy were measured at age 50. Affective symptoms were measured at ages 23, 33, 42 and 50 and used to derive longitudinal trajectories. A structured modelling approach compared a set of nested models in order to test accumulation versus sensitive period hypotheses. Linear regressions and structural equation modelling were used to test for longitudinal associations of affective symptoms with cognitive function.
Accumulation of affective symptoms was found to be the best fit for the data, with persistent affective symptoms being associated with poorer immediate memory (b = −0.07, s.e. = 0.03, P = 0.01), delayed memory (b = −0.13, s.e. = 0.04, P < 0.001) and information processing accuracy (b = 0.18, s.e. = 0.08, P = 0.03), but not with information processing speed (b = 3.15, s.e. = 1.89, P = 0.10). Longitudinal trajectories of repeated affective symptoms were associated with poorer memory, verbal fluency and information processing accuracy.
Persistent affective symptoms can affect cognitive function in mid-life. Effective management of affective disorders to prevent recurrence may reduce risk of poor cognitive outcomes and promote healthy cognitive ageing.
OBJECTIVES: We developed the concept of the extra-territorial
translational team (ETTT) in 2014 as a more inclusive revision and
extension of the team science concept. Translational thinking
is largely marked by the perception of the team as a thing-like structure at the
center of the scientific activity. Collaboration accordingly involves bringing
external others (e.g., scientists, community members, and clinicians) into the
team through limited or dependent participation. The ETTT is intended to frame
the team as an idea: a schema for assembling and managing
relationships among otherwise disparate individuals with
vested interests in the problem at hand. Thus, the ETTT can be seen as a
process as well as an object. Our initial
focus was on the very successful SCI Café program
(where Science and Communities Interact) conducted through the Institute for
Translational Sciences and the Center for Translational Sciences Award at UTMB.
We found that by looking beyond the taken-for-granted features of translational
research teams, we are free to discover new ways of organizing research and
community engagement that are innovative yet productive. The major area of
growth, however, has been the Research, Education, And Community Health
Coalition (REACH). The purpose of the current study is to outline strategies for
inventorying and evaluating the emerging programs that are the major components
of REACH and the SCI Café and to suggest implications for the
extra-territorial translational team concept. METHODS/STUDY
POPULATION: The assessment of the extraterritorial team concept in REACH and SCI
Café is primary a process of qualitative content analysis. We use
semi-structured interviews with project leadership, observations of the actual
performance of the REACH teams, and the review of REACH and SCI Café
documents, for example, Quantitatively, we have conducted a Community Health
Needs Assessment (CHNA) to better understand community health and resource
needs. RESULTS: Both the SCI Café program and the REACH initiative
follow the principles of the ETTT concept for assembling and managing research
and community outreach. The following are several key principles shared by both
programs: (1) The importance of creative, applicable, and inclusive mission
statements: (a) REACH seeks to facilitate communication, collaborative research,
and service efforts between UTMB and Institute for Translational Sciences
investigators and Galveston County community leaders; (b) The SCI
Café hosts interactive dialogs that serve as a medium for priming,
organizing, communicating and strategizing among the individuals involved in
team science via community-based research projects. (2) Increasing scientific
and health literacy: (a) REACH seeks to increase literacy through both
short-term and long-term interactions; (b) The SCI Café focuses on
short-term yet intensive interaction through conversations among researchers,
clinicians, and the public. (3) Sharing timely scientific public health
information with the community: (a) REACH seeks information from community
leaders on relevant topics; (b) The SCI Café can mobilize quickly to
respond to timely topics by direct communication with a wide range of
stakeholders, academic as well as community based. (4) Sharing leadership with
the community: (a) REACH establishes formal relationships with 23 UTMB units and
39 broad-based, high impact Galveston County organizations. (b) The SCI
Café works primarily with “grass roots”
community-level groups and organizations. (5) Creating resources and strategies
for expansion: (a) REACH is working to expand its activities to other counties
in the Gulf Coast area of Texas (e.g., Brazoria and Matagorda Counties); (b) The
SCI Café is expanding its program to comfortable locations accessible
to local residents (e.g., schools and libraries). (6) The value of regular and
systematic scientific and evaluation: (a) REACH is conducting a Community Health
Needs Assessment (CHNA) that has already discovered major issues of relevance to
community leaders including mental health, vaccination rates, food security,
disaster preparedness, and caregiving. (b) The SCI Café conducts an
evaluation survey at the conclusion of every event to stay current with
participants interests and needs. DISCUSSION/SIGNIFICANCE OF IMPACT:
(1) In order to maintain the ability to operate extra-territorially (i.e.,
beyond the safe organizational confines of the University), the 2 programs
discussed here must maintain a fluid team structure. Different projects require
different types of leadership, grass roots participation, university resources,
communications/public relations, etc. (2) The strategy of
accumulating and disseminating best practices appears to be one of the most
valuable products of the extra-territorial team. (a) REACH’s
“Offer and Ask” practice by which information of
university and community resources (skills and expertise) are shared makes
cooperation and shared leadership explicit. (b) The SCI
Café’s interactional strategies for encouraging and
enabling café participants to join the
discussion/conversation are wonderful ways to convert an otherwise
unidirectional lecture into a vibrant conversation. (3) Although the scope of
these 2 programs is quite different, the message from both is that the
principles of extra-territorial translational teams are application to all such
endeavors to improve scientific and health literacy.
OBJECTIVES/SPECIFIC AIMS: The Institute for Transnational Sciences (ITS) has developed novel methods to ethically engage stakeholders across the transnational research spectrum, up to and including public health practice and policy. METHODS/STUDY POPULATION: In 2014, the ITS co-founded The Research, Education, And Community Health (REACH), the mission of which was to facilitate communication, collaborative research, and service activities between faculty and scientists and area community leaders. The intent was to identify and meet the needs of our communities without gaps and/or redundancies, thus better leveraging time, funding, and efforts. RESULTS/ANTICIPATED RESULTS: REACH now boasts 23 Centers, Departments, and Institutes, as well as 39 community organizations, including public and mental health agencies, clinicians, policy makers, family service centers, cultural and faith-based organizations, business, and local schools/colleges. We offer 3 methods for consideration as best practices: (1) a comprehensive community health needs assessment, (2) an “Offer and Ask” community/campus partnership mechanism, and (3) Community Science Workshops, based on the European Union’s Science Shops. DISCUSSION/SIGNIFICANCE OF IMPACT: Results of REACH’s work have been used to provide guidance for enhanced, data-driven programs and allocation of resources for local and statewide initiatives. The organization has evolved into an independent coalition seeking 501(c)3 status and is planning to expand its scope to 5 counties. REACH thus serves as model for successful replication across applicable CTSA hubs.
Objectives: Dysbiosis of the gut microbiome is implicated in numerous human health conditions. Animal studies have linked microbiome disruption to changes in cognitive functioning, although no study has examined this possibility in neurologically healthy older adults. Methods: Participants were 43 community-dwelling older adults (50–85 years) that completed a brief cognitive test battery and provided stool samples for gut microbiome sequencing. Participants performing≥1 SD below normative performance on two or more tests were compared to persons with one or fewer impaired scores. Results: Mann Whitney U tests revealed different distributions of Bacteroidetes (p=.01), Firmicutes (p=.02), Proteobacteria (p=.04), and Verrucomicrobia (p=.003) between Intact and Impaired groups. These phyla were significantly correlated with cognitive test performances, particularly Verrucomicrobia and attention/executive function measures. Conclusions: The current findings suggest that composition of the gut microbiome is associated with cognitive test performance in neurologically healthy older adults. Future studies are needed to confirm these findings and explore possible mechanisms. (JINS, 2017, 23, 700–705)
The subsurface exploration of other planetary bodies can be used to unravel their geological history and assess their habitability. On Mars in particular, present-day habitable conditions may be restricted to the subsurface. Using a deep subsurface mine, we carried out a program of extraterrestrial analog research – MINe Analog Research (MINAR). MINAR aims to carry out the scientific study of the deep subsurface and test instrumentation designed for planetary surface exploration by investigating deep subsurface geology, whilst establishing the potential this technology has to be transferred into the mining industry. An integrated multi-instrument suite was used to investigate samples of representative evaporite minerals from a subsurface Permian evaporite sequence, in particular to assess mineral and elemental variations which provide small-scale regions of enhanced habitability. The instruments used were the Panoramic Camera emulator, Close-Up Imager, Raman spectrometer, Small Planetary Linear Impulse Tool, Ultrasonic drill and handheld X-ray diffraction (XRD). We present science results from the analog research and show that these instruments can be used to investigate in situ the geological context and mineralogical variations of a deep subsurface environment, and thus habitability, from millimetre to metre scales. We also show that these instruments are complementary. For example, the identification of primary evaporite minerals such as NaCl and KCl, which are difficult to detect by portable Raman spectrometers, can be accomplished with XRD. By contrast, Raman is highly effective at locating and detecting mineral inclusions in primary evaporite minerals. MINAR demonstrates the effective use of a deep subsurface environment for planetary instrument development, understanding the habitability of extreme deep subsurface environments on Earth and other planetary bodies, and advancing the use of space technology in economic mining.
To examine realist policy options for the South Australian government to improve food security.
Semi-structured interviews with twenty-four key South Australian food security stakeholders.
Food security is a global issue that affects both developing and developed countries. Governments are well placed to improve food security but the solutions are not always evident.
Policy makers, leaders of non-government organisations, private enterprise and front-line food security workers in South Australia.
The research produced forty-four potential policy options for the South Australian government to improve food security.
Stakeholders offered detailed policy solutions for the local context. This illustrates how gathering local evidence expands understanding on an issue. The process used to generate these policy options is applicable to other public health problems and other contexts.