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A relationship between characteristics of gut microbiota and obesity are now well-established(1). However, less well-understood is the extent to which these microbiological features change during periods of weight loss. This study aimed to investigate the relationship between gut microbiota and weight loss in adults (aged 25 to 65 years, BMI of 27.5 to 34.9 kg/m2) enrolled in a 9-month randomised controlled trial(2). Participants were randomised to consume an energy-restricted diet that was either almond-enriched (30–50 g/daily) or nut-free (carbohydrate-rich snack foods). Data were collected at baseline (BL, n = 108), 3 months (3M, weight loss, n = 87) and 9 months (9M, weight maintenance, n = 82) for body weight, diet composition (weighed food diaries) and faecal microbiota composition (16S rRNA V4 amplicon sequencing). Paired data were analysed using mixed-effects models adjusted for baseline BMI, age, sex, dietary fibre. As reported previously, significant weight loss occurred for both diet groups to an equal extent(3). Significant inverse relationships were observed at BL between BMI and both microbiota richness (number of unique bacterial taxa detected) (estimate = −6.56, 95% CI = −9.9 to −3.19, p = 0.0002) and diversity (Shannon’s index) (−0.06, −0.1 to −0.02, p < 0.001). The strongest relationship at BL involved members of the Christensenellaceae bacterial family, which negatively correlated with BMI (r = −0.26, p = 0.007), consistent with prior studies(3,4). Microbiota richness (8.79, −0.73 to 18.34, p = 0.024) and diversity (0.08, −0.01 to 0.18, p = 0.019) were significantly higher at 9M compared to BL but not at 3M (p > 0.05). Compared to BL, microbiota composition (the taxa detected and their relative abundance) was significantly at 3M (p < 0.001) and 9M (p = 0.007). Following weight loss at 3M, significant increases in the relative abundance of members of the Christensenellaceae and Ruminococcaceae families were observed (log2 fold change > 1, FDR p < 0.05). Positive associations between weight loss and an increase in the relative abundance of Christensenellaceae family was evident at 3M (0.001, 0.0002 to 0.002, p = 0.010), but did not remain significant at 9M. Additionally, weight loss at 3M (0.0002, 1.3 × 10-5 to 0.0005, p = 0.038) and at 9M (0.0002, 4.6 × 10-6 to 0.0005, p = 0.045) was positively associated with an increase in the relative abundance of Lachnospiraceae ND3007, a bacterial genus associated with improved diet quality(5). Our findings demonstrate that the abundance of specific bacterial populations within the gut microbiota change in a manner that is proportionate to weight loss resulting from an energy-restricted diet. The extent to which these microbes are simply markers of altered diet, or whether they contribute in a causal manner to weight loss, as suggested by emerging preclinical data(3), is yet unknown.
Greenhouse studies were conducted from 2020 to 2021 to evaluate the effect of simulated drift rates of 2,4-D and dicamba on strawberry growth, fruit development, and fruit quality in Raleigh, NC. Treatments included 2,4-D choline and dicamba DGA plus Vapor Grip at 1/2×, 1/20×, and 1/200× of the 1× field rate of 1.09 and 0.8 kg ae ha–1, respectively. Treatments were applied to strawberry at three reproductive stages, including bud, flower, and fruit. Averaged across both herbicides, strawberry canopy size was reduced by the 1/2× rate 18, 25, 30, and 36% at 3, 6, 9, and 11 wk after treatment (WAT). The 1/2× rate of both herbicides caused greater injury to strawberry than the 1/20× or 1/200×, with maximum stunting from 2,4-D and dicamba of 54% and 36%, respectively. Fruit pH and total soluble solid content (SSC) increased due to the 1/2× rate of dicamba compared to the 1/20× and 1/200× rates and the nontreated. Treated fruit (across all herbicides) were larger than fruit developing following herbicide application to flowers or buds but were similar to nontreated fruit.
To evaluate the potential superiority of donanemab vs. aducanumab on the percentage of participants with amyloid plaque clearance (≤24.1 Centiloids [CL]) at 6 months in patients with early symptomatic Alzheimer's disease (AD) in phase 3 TRAILBLAZER-ALZ-4 study. The amyloid cascade in AD involves the production and deposition of amyloid beta (Aβ) as an early and necessary event in the pathogenesis of AD.
Methods
Participants (n = 148) were randomized 1:1 to receive donanemab (700 mg IV Q4W [first 3 doses], then 1400 mg IV Q4W [subsequent doses]) or aducanumab (per USPI: 1 mg/kg IV Q4W [first 2 doses], 3 mg/kg IV Q4W [next 2 doses], 6 mg/kg IV Q4W [next 2 doses] and 10 mg/kg IV Q4W [subsequent doses]).
Results
Baseline demographics and characteristics were well-balanced across treatment arms (donanemab [N = 71], aducanumab [N = 69]). Twenty-seven donanemab-treated and 28 aducanumab-treated participants defined as having intermediate tau.
Upon assessment of florbetapir F18 PET scans (6 months), 37.9% donanemab-treated vs. 1.6% aducanumab-treated participants achieved amyloid clearance (p < 0.001). In the intermediate tau subpopulation, 38.5% donanemab-treated vs. 3.8% aducanumab-treated participants achieved amyloid clearance (p = 0.008).
Percent change in brain amyloid levels were −65.2%±3.9% (baseline: 98.29 ± 27.83 CL) and −17.0%±4.0% (baseline: 102.40 ± 35.49 CL) in donanemab and aducanumab arms, respectively (p < 0.001). In the intermediate tau subpopulation, percent change in brain amyloid levels were −63.9%±7.4% (baseline: 104.97 ± 25.68 CL) and −25.4%±7.8% (baseline: 102.23 ± 28.13 CL) in donanemab and aducanumab arms, respectively (p ≤ 0.001).
62.0% of donanemab-treated and 66.7% of aducanumab-treated participants reported an adverse event (AE), there were no serious AEs due to ARIA in donanemab arm and 1.4% serious AEs (one event) due to ARIA were reported in aducanumab arm.
Conclusion
This study provides the first active comparator data on amyloid plaque clearance in patients with early symptomatic AD. Significantly higher number of participants reached amyloid clearance and amyloid plaque reductions with donanemab vs. aducanumab at 6 months.
Previously presented at the Clinical Trials on Alzheimer's Disease - 15th Conference, 2022.
We aim to describe older mens’ experiences with physical activity (PA) and their preferences for PA programs. We interviewed 14 men from a Canada-based PA intervention study called Men on the Move, and 5 men from a supplementary sample (who were not intervention participants). Content analysis was used to describe their experiences with PA and program preferences. The socio-ecological perspective and the hegemonic masculinity framework guided the research. PA barriers were low motivation, poor health, lack of time, interests other than PA and a lack of interest in PA, finances, lack of knowledge about PA, injury fear, social influences, inconvenience, weather, caregiving, built/natural environments, low-quality fitness instructors, and program structure. PA facilitators were chores, health, interest, time, motivation, social influences, active transportation, built/natural environments, good weather, program structure, and skilled/knowledgeable fitness instructors. PA program preferences were small group atmosphere, individualized attention/programming, equal number of men and women, sports programming, PA classes, and experienced instructors. Older men have distinct PA experiences. Promoting and designing programs that address their experiences may increase their PA.
Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.
Methods:
We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.
Results:
BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.
Conclusions:
We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
Field studies were conducted in commercial muscadine vineyards in western North Carolina in 2018 and eastern North Carolina in 2019, 2020, and 2021 to determine tolerance of younger (< 9 yr) and older (≥ 9 yr) bearing muscadine grapevines to 2,4-D directed beneath the crop postemergence (POST). Treatments included 2,4-D choline at 0, 0.53, 1.06, 1.60, and 2.13 kg ae ha−1 applied as a single treatment in May or June (spring) at immediate pre-bloom, and sequential treatments at 0.53 followed by (fb) 0.53, 1.06 fb 1.06, 1.6 fb 1.6, or 2.13 fb 2.13 kg ha−1. The first sequential treatment was applied in spring fb another application of the same amount in July (summer) at pre-veraison. No differences in injury on muscadine grapevines were observed from 2,4-D treatments. Differences among treatments were not observed for yield of younger vines. However, for older vines, a difference due to 2,4-D rate was observed in 2018, when yield was higher when 2,4-D was applied at 1.6 kg ha−1 compared with nontreated grapevines, and when 2,4-D was applied at 0.53 and 2.13 kg ha−1. A rate-by-timing interaction was observed in 2019 when yield was lower from 0.53 kg ha−1 2,4-D summer application compared with all other summer treatments but similar to the nontreated. However, no biological pattern was observed from either of these differences. No differences among treatments were observed for fruit pH, titratable acidity, or soluble solid content of either younger or older vines.
Field studies were conducted on southern highbush blueberry in Elizabethtown and Rocky Point, NC, in 2019, 2020, and 2021 to determine tolerance to 2,4-D choline as a postemergence-directed application. In separate trials for younger and older bearing blueberry bushes, both 2,4-D choline rates and application timing were evaluated. Treatments included 2,4-D choline at 0, 0.53, 1.06, 1.60, and 2.13 kg ae ha–1 applied alone in winter during dormancy, and sequential treatments at 0.53 kg ae ha–1 followed by (fb) 0.53, 1.06 fb 1.06, 1.6 fb 1.6, or 2.13 fb 2.13 kg ae ha–1. The first application of the sequential treatments was applied in winter followed by another application in spring during early green fruit. Injury to blueberry from 2,4-D choline treatments was not observed for either maturity stage, and fruit yield was not affected by any of the treatments. Differences among treatments were not observed for fruit soluble solid content (SSC) in older bushes, or for fruit pH, SSC, and titratable acidity (TA) in younger bushes. In older bushes, fruit pH and TA had rate-by-timing interactions, and TA had a farm-year interaction with differences at Rocky Point in 2019 and Elizabethtown in 2020, but biologically no pattern was observed from the treatments.
Field studies in strawberry grown on polyethylene-mulched raised beds were conducted from 2018 to 2019 and 2019 to 2020 in Clayton, NC, to determine ‘Camarosa’ and ‘Chandler’ strawberry tolerance to 2,4-D directed to the row middle between beds. Treatments included 2,4-D at 0, 0.53, 1.06, 1.60, and 2.13 kg ae ha−1 applied alone and sequential treatments (0.53 followed by [fb] 0.53 or 1.06 fb 1.06 kg ae ha−1). Initial treatments were applied in winter (December 2018 or January 2020) during vegetative growth, and sequential applications were applied in spring (April 2019 or March 2020) during reproductive growth. No differences among treatments were observed for visual foliage injury, strawberry crop canopy, fruit yield, and fruit quality (pH, titratable acidity, and soluble solid content).
Barriers to research participation by racial and ethnic minority group members are multi-factorial, stem from historical social injustices and occur at participant, research team, and research process levels. The informed consent procedure is a key component of the research process and represents an opportunity to address these barriers. This manuscript describes the development of the Strengthening Translational Research in Diverse Enrollment (STRIDE) intervention, which aims to improve research participation by individuals from underrepresented groups.
Methods:
We used a community-engaged approach to develop an integrated, culturally, and literacy-sensitive, multi-component intervention that addresses barriers to research participation during the informed consent process. This approach involved having Community Investigators participate in intervention development activities and using community engagement studios and other methods to get feedback from community members on intervention components.
Results:
The STRIDE intervention has three components: a simulation-based training program directed toward clinical study research assistants that emphasizes cultural competency and communication skills for assisting in the informed consent process, an electronic consent (eConsent) framework designed to improve health-related research material comprehension and relevance, and a “storytelling” intervention in which prior research participants from diverse backgrounds share their experiences delivered via video vignettes during the consent process.
Conclusions:
The community engaged development approach resulted in a multi-component intervention that addresses known barriers to research participation and can be integrated into the consent process of research studies. Results of an ongoing study will determine its effectiveness at increasing diversity among research participants.
We examined the impact of microbiological results from respiratory samples on choice of antibiotic therapy in patients treated for hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP).
Design:
Four-year retrospective study.
Setting:
Veterans’ Health Administration (VHA).
Patients:
VHA patients hospitalized with HAP or VAP and with respiratory cultures between October 1, 2014, and September 30, 2018.
Interventions:
We compared patients with positive and negative respiratory culture results, assessing changes in antibiotic class and Antibiotic Spectrum Index (ASI) from the day of sample collection (day 0) through day 7.
Results:
Between October 1, 2014, and September 30, 2018, we identified 5,086 patients with HAP/VAP: 2,952 with positive culture results and 2,134 with negative culture results. All-cause 30-day mortality was 21% for both groups. The mean time from respiratory sample receipt in the laboratory to final respiratory culture result was longer for those with positive (2.9 ± 1.3 days) compared to negative results (2.5 ± 1.3 days; P < .001). The most common pathogens were Staphylococcus aureus and Pseudomonas aeruginosa. Vancomycin and β-lactam/β-lactamase inhibitors were the most commonly prescribed agents. The decrease in the median ASI from 13 to 8 between days 0 and 6 was similar among patients with positive and negative respiratory cultures. Patients with negative cultures were more likely to be off antibiotics from day 3 onward.
Conclusions:
The results of respiratory cultures had only a small influence on antibiotics used during the treatment of HAP/VAP. The decrease in ASI for both groups suggests the integration of antibiotic stewardship principles, including de-escalation, into the care of patients with HAP/VAP.
This paper reports on a study which examined the notions of authenticity and citizenship for people living with cognitive impairment or dementia in a care home in the North-East of England. We demonstrated that both notions were present and were encouraged by engagement with an artist, where this involved audio and visual recordings and the creation of a film. The artist's interactions were observed by a non-participant observer using ethnographic techniques, including interviews with the residents, their families and the staff of the care home. The data were analysed using grounded theory and the constant comparative method of qualitative analysis. Our findings suggest that participatory art might help to maintain and encourage authenticity and citizenship in people living with dementia in a care home. Certainly, authenticity and citizenship are notions worth pursuing in the context of dementia generally, but especially in care homes.
This paper provides specific guidelines for the neurodevelopmental evaluation of children aged birth through 5 years with complex congenital heart disease. There is wide recognition that children with congenital heart disease are at high risk for neurodevelopmental impairments that are first apparent in infancy and often persist as children mature. Impairments among children with complex congenital heart disease cross developmental domains and affect multiple functional abilities. The guidelines provided are derived from the substantial body of research generated over the past 30 years describing the characteristic developmental profiles and the long-term trajectories of children surviving with complex congenital heart conditions. The content and the timing of the guidelines are consistent with the 2012 American Heart Association and the American Academy of Pediatrics scientific statement documenting the need for ongoing developmental monitoring and assessment from infancy through adolescence. The specific guidelines offered in this article were developed by a multidisciplinary clinical research team affiliated with the Cardiac Neurodevelopmental Outcome Collaborative, a not-for-profit organisation established to determine and implement best neurodevelopmental practices for children with congenital heart disease. The guidelines are designed for use in clinical and research applications and offer an abbreviated core protocol and an extended version that expands the scope of the evaluation. The guidelines emphasise the value of early risk identification, use of evidence-based assessment instruments, consideration of family and cultural preferences, and the importance of providing multidimensional community-based services to remediate risk.
We have previously shown that higher intake of cruciferous vegetables is inversely associated with carotid artery intima-media thickness. To further test the hypothesis that an increased consumption of cruciferous vegetables is associated with reduced indicators of structural vascular disease in other areas of the vascular tree, we aimed to investigate the cross-sectional association between cruciferous vegetable intake and extensive calcification in the abdominal aorta. Dietary intake was assessed, using a FFQ, in 684 older women from the Calcium Intake Fracture Outcome Study. Cruciferous vegetables included cabbage, Brussels sprouts, cauliflower and broccoli. Abdominal aortic calcification (AAC) was scored using the Kauppila AAC24 scale on dual-energy X-ray absorptiometry lateral spine images and was categorised as ‘not extensive’ (0–5) or ‘extensive’ (≥6). Mean age was 74·9 (sd 2·6) years, median cruciferous vegetable intake was 28·2 (interquartile range 15·0–44·7) g/d and 128/684 (18·7 %) women had extensive AAC scores. Those with higher intakes of cruciferous vegetables (>44·6 g/d) were associated with a 46 % lower odds of having extensive AAC in comparison with those with lower intakes (<15·0 g/d) after adjustment for lifestyle, dietary and CVD risk factors (ORQ4 v. Q1 0·54, 95 % CI 0·30, 0·97, P = 0·036). Total vegetable intake and each of the other vegetable types were not related to extensive AAC (P > 0·05 for all). This study strengthens the hypothesis that higher intake of cruciferous vegetables may protect against vascular calcification.
Abnormalities in glutamate signaling and glutamate toxicity are thought to be important in the pathophysiology of bipolar disorder (BD). Whilst previous studies have found brain white matter changes in BD, there is paucity of data about how glutamatergic genes affect brain white matter integrity in BD. Based on extant neuroimaging data, we hypothesized that GRIN2B risk allele is associated with reductions of brain white matter integrity in the frontal, parietal, temporal, occipital regions and cingulate gyrus in BD. Fourteen patients with BD and 22 age, gender, handedness matched healthy controls were genotyped using blood samples and underwent diffusion tensor imaging. Compared to G allele, brain FA values were significantly lower in BD patients with risk T allele in left frontal region (p = 0.001), right frontal region (p =0.002), left parietal region (p = 0.001), left occipital region (p = 0.001), right occipital region (p <0.001), left cingulate gyrus (p = 0.001). Further elucidation of the interactions between different glutamate genes and their relationships with such structural, functional brain substrates will enhance our understanding of the link between dysregulated glutamatergic neurotransmission and neuroimaging endophenotypes in BD.
The Kraepelinian dichotomy posits that patients with schizophrenia (SCZ) and bipolar disorder (BD) present as two separate psychotic entities such that they differ in terms of clinical severity including neurocognitive functioning. Based on clinical impression within a tertiary psychiatric hospital context and extant data, we hypothesized that patients with SCZ had a similar level of neurcognitive impairment compared with BD. Forty-nine healthy controls (HC), 72 SCZ and 42 BD patients who were matched for age, gender, and premorbid IQ were administered the Brief Assessment of Cognition battery (BAC), the Positive and Negative Syndrome Scale for SCZ patients, the Young Mania Rating Scale (YMRS) for BD patients, and Global Assessment of Functioning (GAF) for both patients groups. Both BD and SCZ groups demonstrated similar patterns of neurocognitive deficits across several domains (verbal memory, working memory, semantic fluency, processing speed) compared with HC subjects. However, no significant difference was found in neurocognitive functioning between BD and SCZ patients, suggesting that both patient groups suffer the same degree of neurocognitive impairment. Moreover, patients with lower level of psychosocial functioning as indicated by lower GAF score (F(1,112) = 2.661, p = 0.009) and older age (F(1,112) = −2.625, p = 0.010), not diagnosis or doses of psychotropic medications, predicted were associated with poorer overall neurocognitive functioning as measured by the(lower BAC composite score). Our findings of comparable neurocognitive impairments between SCZ and BD affirm our hypothesis and support less the Kraepelinian concept of dichotomy but more of a continuum of psychotic spectrum conditions.
The conclusive prognostic significance of cyclo-oxygenase-2 has been determined in various cancers but not in nasopharyngeal carcinoma. Therefore, this study aimed to evaluate the relationship of cyclo-oxygenase-2 expression with the survival outcome and treatment response of nasopharyngeal carcinoma patients via a systematic meta-analysis approach.
Methods
A meta-analysis was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (‘PRISMA’) checklist. The primary clinical characteristics of patients, and hazard ratios with 95 per cent confidence intervals of overall survival data, were tabulated from eligible studies. The relationship of cyclo-oxygenase-2 expression with survival outcome (expressed as hazard ratio) and treatment response (expressed as odds ratio) in nasopharyngeal carcinoma patients was analysed, and explained with the aid of forest plot charts.
Results and conclusion
The pooled hazard ratio for overall survival was 2.02 (95 per cent confidence interval = 1.65–2.47). This indicates that the over-expression of cyclo-oxygenase-2 is significantly associated with the poor survival of nasopharyngeal carcinoma patients. The pooled odds ratio of 0.98 (95 per cent confidence interval = 0.27–3.49) reveals that over-expression of cyclo-oxygenase-2 was not significantly related to the treatment outcome.
Non-tuberculous mycobacterium encephalitis is rare. Since 2013, a global outbreak of Mycobacterium chimaera infection has been attributed to point-source contamination of heater cooler units used in cardiac surgery. Disseminated M. chimaera infection has presented many unique challenges, including non-specific clinical presentations with delays in diagnosis, and a high mortality rate among predominantly immunocompetent adults. Here, we describe three patients with fatal disseminated Mycobacterium chimaera infection showing initially non-specific, progressively worsening neurocognitive decline, including confusion, delirium, depression and apathy. Autopsy revealed widespread granulomatous encephalitis of the cerebrum, brain stem and spinal cord, along with granulomatous chorioretinitis. Cerebral involvement and differentiation between mycobacterial granulomas and microangiopathic changes can be assessed best on MRI with contrast enhancement. The prognosis of M. chimaera encephalitis appears to be very poor, but might be improved by increased awareness of this new syndrome and timely antimicrobial treatment.
LEARNING OBJECTIVES
This presentation will enable the learner to:
1. Describe the clinical, radiological and neuropathological findings of Mycobacterium chimaera encephalitis
2. Be aware of this rare form of encephalitis, and explain its diagnosis, prognosis and management
This study aimed to determine the relationship between laryngopharyngeal reflux and dietary modification.
Methods
A systematic review was conducted. The data sources for the study were PubMed, Embase, Cochrane Library and Web of Science. Articles were independently extracted by two authors according to inclusion and exclusion criteria. The outcome focus was laryngopharyngeal reflux improvement through diet or dietary behaviour.
Results
Of the 372 studies identified, 7 met our inclusion criteria. In these seven studies, laryngopharyngeal reflux symptoms improved following dietary modifications. However, the studies did not present the independent effect of each dietary factor on laryngopharyngeal reflux. Moreover, only one of the seven studies had a randomised controlled study design.
Conclusion
The reference studies of dietary modification for laryngopharyngeal reflux patients are not sufficient to provide recommendations.