ABSTRACT
In this study of postmenopausal women in Malaysia, total adiposity was inversely associated with total BMD, while regional associations varied. No differences were detected across Malay, Chinese, and Indian ethnicities. Low BMD contributes substantially to morbidity and mortality, and increasing adiposity levels globally may be contributing to this. PURPOSE: To investigate associations of total and regional adiposity with bone mineral density (BMD) among a multi-ethnic cohort of postmenopausal women. METHODS: Dual X-ray absorptiometry (DXA) imaging was undertaken for 1990 postmenopausal women without prior chronic diseases (30% Malay, 53% Chinese, and 17% Indian) from The Malaysian Cohort (TMC). The strength of the associations between standardized total and regional body fat percentages with total and regional BMD was examined using linear regression models adjusted for age, height, lean mass, ethnicity, education, and diabetes. Effect modification was assessed for ethnicity. RESULTS: Women with a higher total body fat percentage were more likely to be Indian or Malay. Mean (SD) BMD for the whole-body total, lumbar spine, leg, and arm were 1.08 (0.11), 0.96 (0.15), 2.21 (0.22), and 1.36 (0.12) g/cm2, respectively. Total body and visceral fat percentage were inversely associated with total BMD (- 0.02 [95% CI - 0.03, - 0.01] and - 0.01 [- 0.02, - 0.006] g/cm2 per 1 SD, respectively). In contrast, subcutaneous and gynoid fat percentages were positively associated with BMD (0.007 [0.002, 0.01] and 0.01 [0.006, 0.02] g/cm2, respectively). Total body fat percentage showed a weak positive association with lumbar BMD (0.01 [0.004, 0.02]) and inverse associations with leg (- 0.04 [- 0.06, - 0.03]) and arm (- 0.02 [- 0.03, - 0.02]) BMD in the highest four quintiles. There was no effect modification by ethnicity (phetero > 0.05). CONCLUSION: Total adiposity was inversely associated with total BMD, although regional associations varied. There was no heterogeneity across ethnic groups suggesting adiposity may be a risk factor for low BMD across diverse populations.
Subject(s)
Absorptiometry, Photon , Bone Density , Postmenopause , Humans , Female , Malaysia/ethnology , Malaysia/epidemiology , Middle Aged , Postmenopause/physiology , Postmenopause/ethnology , Aged , Cohort Studies , Body Fat Distribution/statistics & numerical data , Ethnicity/statistics & numerical data , Lumbar Vertebrae/diagnostic imaging , Adiposity/ethnology , Adiposity/physiologyABSTRACT
BACKGROUND: Fruit consumption has been associated with a lower cardiovascular disease (CVD) risk but the underlying mechanisms are unclear. We investigated the cross-sectional and prospective associations of fruit consumption with markers of adiposity, blood pressure, lipids, low-grade inflammation, glycaemia, and oxidative stress. METHODS: The main analyses included 365 534 middle-aged adults from the UK Biobank at baseline, of whom 11 510, and 38 988 were included in the first and second follow-up respectively, free from CVD and cancer at baseline. Fruit consumption frequency at baseline was assessed using a questionnaire. We assessed the cross-sectional and prospective associations of fruit with adiposity (body mass index, waist circumference and %body fat), systolic and diastolic blood pressure, lipids (low-density and high-density lipoproteins, triglycerides and apolipoprotein B), glycaemia (haemoglobin A1c), low-grade inflammation (C-reactive protein) and oxidative stress (gamma-glutamyl-transferase) using linear regression models adjusted for socioeconomic and lifestyle factors. Analyses were repeated in a subset with two to five complete 24-h dietary assessments (n = 26 596) allowing for adjustment for total energy intake. RESULTS: Fruit consumption at baseline generally showed weak inverse associations with adiposity and biomarkers at baseline. Most of these relationships did not persist through follow-up, except for inverse associations with diastolic blood pressure, C-reactive protein, gamma-glutamyl transferase and adiposity. However, for most mechanisms, mean levels varied by less than 0.1 standard deviations (SD) between high and low fruit consumption (> 3 vs < 1 servings/day) in further adjusted models (while the difference was < 0.2 SD for all of them). For example, waist circumference and diastolic blood pressure were 1 cm and 1 mmHg lower in high compared to low fruit intake at the first follow-up (95% confidence interval: -1.8, -0.1 and -1.8, -0.3, respectively). Analyses in the 24-h dietary assessment subset showed overall similar associations. CONCLUSIONS: We observed very small differences in adiposity and cardiometabolic biomarkers between those who reported high fruit consumption vs low, most of which did not persist over follow-up. Future studies on other mechanisms and detailed assessment of confounding might further elucidate the relevance of fruit to cardiovascular disease.
Subject(s)
Adiposity , Biomarkers , Fruit , Humans , Male , United Kingdom/epidemiology , Female , Middle Aged , Biomarkers/blood , Cross-Sectional Studies , Prospective Studies , Biological Specimen Banks , Blood Pressure/physiology , Cardiovascular Diseases/epidemiology , Cardiometabolic Risk Factors , Diet/statistics & numerical data , Adult , Oxidative Stress/physiology , Lipids/blood , UK BiobankABSTRACT
Impaired behavioural flexibility is a core feature of neuropsychiatric disorders and is associated with underlying dysfunction of fronto-striatal circuitry. Reduced dosage of Cyfip1 is a risk factor for neuropsychiatric disorder, as evidenced by its involvement in the 15q11.2 (BP1-BP2) copy number variant: deletion carriers are haploinsufficient for CYFIP1 and exhibit a two- to four-fold increased risk of schizophrenia, autism and/or intellectual disability. Here, we model the contributions of Cyfip1 to behavioural flexibility and related fronto-striatal neural network function using a recently developed haploinsufficient, heterozygous knockout rat line. Using multi-site local field potential (LFP) recordings during resting state, we show that Cyfip1 heterozygous rats (Cyfip1+/-) harbor disrupted network activity spanning medial prefrontal cortex, hippocampal CA1 and ventral striatum. In particular, Cyfip1+/- rats showed reduced influence of nucleus accumbens and increased dominance of prefrontal and hippocampal inputs, compared to wildtype controls. Adult Cyfip1+/- rats were able to learn a single cue-response association, yet unable to learn a conditional discrimination task that engages fronto-striatal interactions during flexible pairing of different levers and cue combinations. Together, these results implicate Cyfip1 in development or maintenance of cortico-limbic-striatal network integrity, further supporting the hypothesis that alterations in this circuitry contribute to behavioural inflexibility observed in neuropsychiatric diseases including schizophrenia and autism.
Subject(s)
Adaptor Proteins, Signal Transducing , Haploinsufficiency , Prefrontal Cortex , Schizophrenia , Animals , Rats , Schizophrenia/genetics , Schizophrenia/physiopathology , Male , Adaptor Proteins, Signal Transducing/genetics , Prefrontal Cortex/physiopathology , Autistic Disorder/genetics , Autistic Disorder/physiopathology , CA1 Region, Hippocampal/physiopathology , Disease Models, Animal , Nerve Net/physiopathology , Behavior, Animal/physiology , Corpus Striatum/physiopathology , Ventral Striatum/physiopathologyABSTRACT
BACKGROUND: The relevance of measures of general and central adiposity for cardiovascular disease (CVD) risks in populations of European descent is well established. However, it is less well characterised in South Asian populations, who characteristically manifest larger waist circumferences (WC) for equivalent body mass index (BMI). This systematic review and meta-analysis provide an overview of the literature on the association of different anthropometric measures with CVD risk among South Asians. METHODOLOGY: MEDLINE and Embase were searched from 1990 to the present for studies in South Asian populations investigating associations of two or more adiposity measures with CVD. Random-effects meta-analyses were conducted on the associations of BMI, WC and waist-to-hip ratio (WHR) with blood pressure, hypertension and CVD. Quality assessment was performed using the Newcastle-Ottawa scale. RESULTS: Titles and abstracts were screened for 7327 studies, yielding 147 full-text reviews. The final sample (n=30) included 2 prospective, 5 case-control and 23 cross-sectional studies. Studies reported generally higher risks of hypertension and CVD at higher adiposity levels. The pooled mean difference in systolic blood pressure (SBP) per 5 kg/m2 higher BMI was 3 mmHg (2.90 (95% CI 1.30 to 4.50)) and 6 mmHg (6.31 (95% CI 4.81 to 7.81) per 13 cm larger WC. The odds ratio (OR) of hypertension per 5 kg/m2 higher BMI was 1.33 (95% CI 1.18 to 1.51), 1.45 (95% CI 1.05 to 1.98) per 13 cm larger WC and 1.22 (95% CI 1.04 to 1.41) per 0.1-unit larger WHR. Pooled risk of CVD for BMI-defined overweight versus healthy-weight was 1.65 (95% CI 1.55 to 1.75) and 1.48 (95% CI 1.21 to 1.80) and 2.51 (95% CI 0.94 to 6.69) for normal versus large WC and WHR, respectively. Study quality was average with significant heterogeneity. CONCLUSIONS: Measures of both general and central adiposity had similar, strong positive associations with the risk of CVD in South Asians. Larger prospective studies are required to clarify which measures of body composition are more informative for targeted CVD primary prevention in this population.
Subject(s)
Cardiovascular Diseases , Hypertension , Humans , Adiposity/physiology , Cross-Sectional Studies , Prospective Studies , Risk Factors , Hypertension/complications , Obesity/epidemiology , Obesity, Abdominal/complications , Obesity, Abdominal/epidemiology , Waist-Hip Ratio , Waist Circumference , Body Mass IndexABSTRACT
BACKGROUND AND AIMS: Excess energy intake can lead to metabolic dysfunction-associated steatotic liver disease (MASLD), but the relationship between dietary carbohydrate intake and liver fat content remains unclear. This study aimed to examine the associations between types and sources of dietary carbohydrates and liver fat content. METHODS: UK Biobank participants with no pre-existing diabetes, liver disease or cardiovascular disease reported dietary intake of types and sources of carbohydrates (total carbohydrates, free sugars, non-free sugars, starch from whole grains, starch from refined grains, and fibre) on at least two 24-h dietary assessments. In cross-sectional analyses, (n = 22,973), odds ratios (OR) of high liver fat content (defined as a score of ≥ 36 in the hepatic steatosis index) by quintiles of carbohydrate intakes were estimated using multivariable logistic regression models. In prospective analyses, a second sample (n = 9268) had liver proton density fat fraction (PDFF) measured by magnetic resonance imaging (2014-2020). Multivariable linear regression models estimated geometric means of PDFF (%) by quintiles of carbohydrate intakes. Models were adjusted for demographic and lifestyle confounders, including total energy intake. RESULTS: In the cross-sectional analyses, 6894 cases of high liver fat content were identified. Inverse associations between intakes of fibre (OR of highest vs. lowest quintile 0.46 [95% CI: 0.41-0.52]), non-free sugars (0.63 [0.57-0.70]) and starch from whole grains (0.52 [0.47-0.57]) with liver fat were observed. There were positive associations between starch from refined grains and liver fat (1.33 [1.21-1.46]), but no association with free sugars (p=0.61). In prospective analyses, inverse associations with PDFF (%) were observed for intakes of fibre (- 0.48 geometric mean difference between highest and lowest quintile of intake [- 0.60 to - 0.35]), non-free sugars (- 0.37 [- 0.49 to - 0.25]) and starch from whole grains (- 0.31 [- 0.42 to - 0.19]). Free sugars, but not starch from refined grains, were positively associated with PDFF (0.17 [0.05 to 0.28]). CONCLUSION: This study suggests that different carbohydrate types and sources have varying associations with liver fat, which may be important for MASLD prevention. Non-free sugars, fibre, and starch from whole grains could be protective, while associations with free sugars and starch from refined grains are less clear.
Subject(s)
Dietary Carbohydrates , Liver Diseases , Humans , Diet/adverse effects , Prospective Studies , Cross-Sectional Studies , Biological Specimen Banks , Starch , Sugars , United KingdomABSTRACT
Leishmaniases are a collection of neglected tropical diseases caused by kinetoplastid parasites in the genus Leishmania. Current chemotherapies are severely limited, and the need for new antileishmanials is of pressing international importance. Bromodomains are epigenetic reader domains that have shown promising therapeutic potential for cancer therapy and may also present an attractive target to treat parasitic diseases. Here, we investigate Leishmania donovani bromodomain factor 5 (LdBDF5) as a target for antileishmanial drug discovery. LdBDF5 contains a pair of bromodomains (BD5.1 and BD5.2) in an N-terminal tandem repeat. We purified recombinant bromodomains of L. donovani BDF5 and determined the structure of BD5.2 by X-ray crystallography. Using a histone peptide microarray and fluorescence polarization assay, we identified binding interactions of LdBDF5 bromodomains with acetylated peptides derived from histones H2B and H4. In orthogonal biophysical assays including thermal shift assays, fluorescence polarization, and NMR, we showed that BDF5 bromodomains bind to human bromodomain inhibitors SGC-CBP30, bromosporine, and I-BRD9; moreover, SGC-CBP30 exhibited activity against Leishmania promastigotes in cell viability assays. These findings exemplify the potential BDF5 holds as a possible drug target in Leishmania and provide a foundation for the future development of optimized antileishmanial compounds targeting this epigenetic reader protein.
Subject(s)
Antiprotozoal Agents , Factor V , Humans , Factor V/metabolism , Histones/chemistry , Histones/metabolism , Protein Domains , Antiprotozoal Agents/pharmacology , Drug Discovery , Transcription Factors/metabolismABSTRACT
BACKGROUND: No large-scale studies have compared associations between body composition and cardiovascular risk factors across multi-ethnic populations. METHODS: Population-based surveys included 30,721 Malay, 10,865 Indian and 25,296 Chinese adults from The Malaysian Cohort, and 413,737 White adults from UK Biobank. Sex-specific linear regression models estimated associations of anthropometry and body composition (body mass index [BMI], waist circumference [WC], fat mass, appendicular lean mass) with systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), triglycerides and HbA1c. RESULTS: Compared to Malay and Indian participants, Chinese adults had lower BMI and fat mass while White participants were taller with more appendicular lean mass. For BMI and fat mass, positive associations with SBP and HbA1c were strongest among the Chinese and Malay and weaker in White participants. Associations with triglycerides were considerably weaker in those of Indian ethnicity (eg 0.09 [0.02] mmol/L per 5 kg/m2 BMI in men, vs 0.38 [0.02] in Chinese). For appendicular lean mass, there were weak associations among men; but stronger positive associations with SBP, triglycerides, and HbA1c, and inverse associations with LDL-C, among Malay and Indian women. Associations between WC and risk factors were generally strongest in Chinese and weakest in Indian ethnicities, although this pattern was reversed for HbA1c. CONCLUSION: There were distinct patterns of adiposity and body composition and cardiovascular risk factors across ethnic groups. We need to better understand the mechanisms relating body composition with cardiovascular risk to attenuate the increasing global burden of obesity-related disease.
Subject(s)
Cardiovascular Diseases , Ethnicity , Male , Adult , Humans , Female , Cholesterol, LDL , Glycated Hemoglobin , Risk Factors , Body Composition , Obesity/complications , Body Mass Index , Cardiovascular Diseases/complications , Triglycerides , Waist Circumference , Blood Pressure , Heart Disease Risk FactorsABSTRACT
BACKGROUND: Unhealthy dietary patterns (DP) have been frequently linked to avoidable ill-health, mediated in part through higher body mass index. However it is unclear how these patterns relate to specific components of body composition or fat distribution, and whether this may explain reported gender differences in the relationship between diet and health. METHODS: Data from 101,046 UK Biobank participants with baseline bioimpedance analysis and anthropometric measures and dietary information on two or more occasions were used, of which 21,387 participants had repeated measures at follow up. Multivariable linear regressions estimated the associations between DP adherence (categorised in quintiles Q1-Q5) and body composition measures adjusted for a range of demographic and lifestyle confounders. RESULTS: After 8.1 years of follow-up, individuals with high adherence (Q5) to the DP showed significantly positive changes in fat mass (mean, 95 % CI): 1.26 (1.12-1.39) kg in men, 1.11 (0.88-1.35) kg in women vs low adherence (Q1) - 0.09 (- 0.28 to 0.10) kg in men and - 0.26 (- 0.42 to - 0.11) kg in women; as well as in waist circumference (Q5): 0.93 (0.63-1.22) cm in men and 1.94 (1.63, 2.25) cm in women vs Q1 - 1.06 (- 1.34 to - 0.78) cm in men and 0.27 (- 0.02 to 0.57) cm in women. CONCLUSION: Adherence to an unhealthy DP is positively associated with increased adiposity, especially in the abdominal region, which may help explain the observed associations with adverse health outcomes.
Subject(s)
Adiposity , Biological Specimen Banks , Male , Humans , Female , Obesity , Diet , Body Composition , United KingdomABSTRACT
BACKGROUND: Recent studies have reported that the associations between dietary carbohydrates and cardiovascular disease (CVD) may depend on the quality, rather than the quantity, of carbohydrates consumed. This study aimed to assess the associations between types and sources of dietary carbohydrates and CVD incidence. A secondary aim was to examine the associations of carbohydrate intakes with triglycerides within lipoprotein subclasses. METHODS: A total of 110,497 UK Biobank participants with ≥ two (maximum five) 24-h dietary assessments who were free from CVD and diabetes at baseline were included. Multivariable-adjusted Cox regressions were used to estimate risks of incident total CVD (4188 cases), ischaemic heart disease (IHD; 3138) and stroke (1124) by carbohydrate intakes over a median follow-up time of 9.4 years, and the effect of modelled dietary substitutions. The associations of carbohydrate intakes with plasma triglycerides within lipoprotein subclasses as measured by nuclear magnetic resonance (NMR) spectroscopy were examined in 26,095 participants with baseline NMR spectroscopy measurements. RESULTS: Total carbohydrate intake was not associated with CVD outcomes. Free sugar intake was positively associated with total CVD (HR; 95% CI per 5% of energy, 1.07;1.03-1.10), IHD (1.06;1.02-1.10), and stroke (1.10;1.04-1.17). Fibre intake was inversely associated with total CVD (HR; 95% CI per 5 g/d, 0.96;0.93-0.99). Modelled isoenergetic substitution of 5% of energy from refined grain starch with wholegrain starch was inversely associated with total CVD (0.94;0.91-0.98) and IHD (0.94;0.90-0.98), and substitution of free sugars with non-free sugars was inversely associated with total CVD (0.95;0.92-0.98) and stroke (0.91;0.86-0.97). Free sugar intake was positively associated with triglycerides within all lipoproteins. CONCLUSIONS: Higher free sugar intake was associated with higher CVD incidence and higher triglyceride concentrations within all lipoproteins. Higher fibre intake and replacement of refined grain starch and free sugars with wholegrain starch and non-free sugars, respectively, may be protective for incident CVD.
Subject(s)
Cardiovascular Diseases , Myocardial Ischemia , Stroke , Humans , Dietary Carbohydrates/adverse effects , Dietary Carbohydrates/analysis , Risk Factors , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/complications , Prospective Studies , Biological Specimen Banks , Diet/adverse effects , Triglycerides , Edible Grain/chemistry , Starch/analysis , Stroke/etiology , United Kingdom/epidemiologyABSTRACT
Background Uncertainty persists about carotid intima-media thickness (CIMT) as a marker of subclinical atherosclerosis and the independent relevance of different measures of adiposity for CIMT. We assessed the independent relevance of general adiposity (body mass index), central adiposity (waist circumference), and body composition (fat mass index and fat-free mass index) with CIMT among adults in the United Kingdom. Methods and Results Multivariable linear regression of cross-sectional analyses of UK Biobank assessed the mean percentage difference in CIMT associated with equivalent differences in adiposity measures. To assess independent associations, body mass index and waist circumference were mutually adjusted, as were fat mass index and fat-free mass index. Among 39 367 participants (mean [SD] age 64 [8] years, 52% female, 97% White), median (interquartile range) CIMT was 0.65 (0.14) mm in women and 0.69 (0.18) mm in men. All adiposity measures were linearly and positively associated with CIMT after adjusting for confounders. Fat-free mass index was most strongly associated with CIMT after adjustment for fat mass index (% difference in CIMT: 1.23 [95% CI 0.93-1.53] women; 3.44 [3.01-3.86] men), while associations of fat mass index were attenuated after adjustment for fat-free mass index (0.28 [-0.02, 0.58] women; -0.59 [-0.99, -0.18] men). After mutual adjustment, body mass index remained positively associated with CIMT, but waist circumference was completely attenuated. Conclusions Fat-free mass index was the adiposity measure most strongly associated with CIMT, suggesting that CIMT may reflect vascular compensatory remodeling rather than atherosclerosis. Hence, screening for subclinical atherosclerosis should evaluate carotid plaques in addition to CIMT.
Subject(s)
Adiposity , Atherosclerosis , Carotid Artery Diseases , Female , Humans , Male , Middle Aged , Atherosclerosis/diagnostic imaging , Atherosclerosis/epidemiology , Biological Specimen Banks , Body Mass Index , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/epidemiology , Carotid Intima-Media Thickness , Cross-Sectional Studies , Obesity/diagnosis , Obesity/epidemiology , Risk Factors , AgedABSTRACT
Cortical bone allograft sterilized with a standard γ-radiation dose of 25-35kGy has demonstrated reduced static and cyclic fracture resistance compared with unirradiated bone. To mitigate radiation damage, we recently observed a dose-dependent response of high-cycle fatigue behavior of human cortical bone from 0 to 25 kGy, with lower doses exhibiting logarithmically longer fatigue lives. The objectives of this study were as follows: (1) to determine whether fracture toughness, work-to-fracture, and fatigue crack propagation resistance of human cortical bone are also radiation dose-dependent, and (2) to determine the associations of radiation dose and a Raman biomarker for collagen disorder with fracture properties. Compact tension specimens were machined from two donor femoral pairs and allocated to four treatment groups: 0 (unirradiated control), 10, 17.5, and 25 kGy. Fracture toughness specimens were monotonically loaded to failure and the critical stress intensity factor (KC ) was determined. Work-to-fracture was calculated from the load versus displacement integral up to fracture. Fatigue crack propagation specimens were cyclically loaded under constant room-temperature irrigation and fatigue crack growth rate (da/dN) and cyclic stress intensity (∆K) were calculated. Fracture toughness, work-to-fracture, and fatigue crack propagation resistance decreased 18%, 33%, and 15-fold from 0 to 25 kGy, respectively (p < 0.05). Radiation dose was more predictive of fracture properties than collagen disorder. These findings support that quasi-static and fatigue fracture properties of cortical bone are radiation dose-dependent within this dose range. The structural alterations arising from irradiation that cause these losses in fracture resistance remain to be elucidated.
Subject(s)
Bone and Bones , Fractures, Stress , Humans , Cortical Bone , Collagen , Radiation Dosage , Stress, MechanicalABSTRACT
Objective: To determine if a resilience training program improved knowledge of and intention to use adaptive coping strategies among college student-athletes; and explore college student-athletes' experiences and satisfaction with program components. Participants: Division I college student-athletes. Methods: Pretest-posttest design with surveys completed at baseline and immediately post-program. Results: A total of 79 participants were included (n = 43 [54.4%] females; n = 36 [45.6%] males; Mage = 20.94, [SD = 1.05]). Overall intention to use adaptive coping strategies significantly increased from baseline (M = 29.05, SD = 4.50) to post-program (M = 32.38, SD = 5.62) (p = 0.0004), as did intentions to use the coping strategies seeking social support (p = 0.0037) and self-controlling (p = 0.0007). We found no statistically significant differences in knowledge scores from baseline to post-program. Conclusions: Resilience training may increase college student-athletes' likelihood of using adaptive coping strategies to manage academic and sport-related stressors.
Subject(s)
Sports , Students , Male , Female , Humans , Young Adult , Adult , Pilot Projects , Universities , AthletesABSTRACT
Importance: Uncertainty persists regarding the independent association of general and central adiposity with major stroke types. Objective: To determine the independent associations of general and central adiposity with risk of ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Design, Setting, and Participants: Between 2006 and 2010, adults without prior stroke at recruitment in England, Scotland, and Wales were recruited into the UK Biobank prospective cohort study and were followed up through linkage with electronic medical records. Data were analyzed from September 2021 to September 2022. Exposures: General adiposity (body mass index [BMI] calculated as weight in kilograms divided by height in meters squared) and central adiposity (waist circumference). Main Outcomes and Measures: Incident ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage as recorded through record linkage with electronic hospital records. Cox regression estimated adjusted hazard ratios (HRs) by stroke type. Results: Among 490â¯071 participants, the mean (SD) age was 56.5 (8.1) years, 267â¯579 (54.6%) were female, and 461â¯647 (94.2%) were White. During a median (IQR) of 12 (11.2-12.7) years follow-up, 7117 incident ischemic strokes, 1391 intracerebral hemorrhages, and 834 subarachnoid hemorrhages were identified. After mutual adjustment for waist circumference, BMI had no independent association with ischemic stroke (HR per 5-unit higher BMI, 1.04; 95% CI, 0.97-1.11), but was inversely associated with intracerebral hemorrhage (HR, 0.85; 95% CI, 0.74-0.96) and subarachnoid hemorrhage (HR, 0.82; 95% CI, 0.69-0.96). Waist circumference (adjusted for BMI) was positively associated with ischemic stroke (HR per 10-cm higher waist circumference, 1.19; 95% CI, 1.13-1.25) and intracerebral hemorrhage (HR, 1.17; 95% CI, 1.05-1.30), but was not associated with subarachnoid hemorrhage (HR, 1.07; 95% CI, 0.93-1.22). Conclusions and Relevance: In this large-scale prospective study, the independent and contrasting associations of BMI and waist circumference with stroke types suggests the importance of considering body fat distribution to stroke risk. Waist circumference was positively associated with the risk of ischemic stroke and intracerebral hemorrhage, while BMI was inversely associated with the risk of subarachnoid hemorrhage and intracerebral hemorrhage. This study also suggests that some adverse correlate of low BMI may be associated with an increased risk of intracerebral hemorrhage and subarachnoid hemorrhage, which warrants further investigation.
Subject(s)
Hemorrhagic Stroke , Ischemic Stroke , Stroke , Subarachnoid Hemorrhage , Adult , Female , Humans , Middle Aged , Male , Adiposity , Prospective Studies , Subarachnoid Hemorrhage/etiology , Subarachnoid Hemorrhage/complications , Obesity/complications , Stroke/etiology , Stroke/complications , United Kingdom/epidemiology , Cerebral Hemorrhage/epidemiology , Obesity, Abdominal/complications , Ischemic Stroke/complicationsABSTRACT
The Oxford WebQ is an online 24 h dietary assessment tool used by several large prospective studies. This study describes the creation of the new individual fatty acid (FA) dataset for the Oxford WebQ and reports intakes and sources of dietary individual FAs in the UK Biobank. Participants who completed ≥1 (maximum of five) 24 h dietary assessments were included (n = 207,997). Nutrient intakes were obtained from the average of all completed 24 h dietary assessments. Nutrient data from the UK McCance and Widdowson's The Composition of Foods and the US Department of Agriculture food composition tables were used to calculate intakes of 21 individual FAs. The individual FA dataset included 10 saturated fatty acids (SFAs), 4 monounsaturated fatty acids (MUFAs), and 7 polyunsaturated fatty acids (PUFAs; including alpha-linolenic (18:3), eicosapentaenoic (20:5), and docosahexaenoic (22:6) acids). Palmitic (16:0; mean ± standard deviation (SD): 13.5 ± 5.7 g/d) and stearic (18:0; 5.2 ± 2.5) acids were the main contributors to SFAs, and the main sources of these were cereals and cereal products (mostly desserts/cakes/pastries), milk and milk products (mostly cheese and milk), and meat and meat products. Oleic acid (18:1; 24.2 ± 9.8) was the main MUFA, derived mainly from cereals and cereal products, and meat and meat products. Linoleic acid (18:2; 9.7 ± 4.3) was the main PUFA, derived mostly from cereals and cereal products, and vegetables (including potatoes) and vegetable dishes. The individual FA dataset for the Oxford WebQ will allow future investigations on individual FAs and disease risk.
Subject(s)
Biological Specimen Banks , Fatty Acids , Diet , Fatty Acids, Monounsaturated , Fatty Acids, Unsaturated , Humans , Prospective Studies , United KingdomABSTRACT
The long-lived positron emitter 89Zr is a highly promising nuclide employed in diagnostic Positron Emission Tomography (PET) imaging. Methods of radiochemical processing to obtain 89Zr for clinical use are traditionally performed with a single hydroxamate resin column. Herein, we present a tandem column purification method for the preparation of high-purity 89Zr from cyclotron bombarded natural Y metal foils. The primary column is a macroporous, strongly basic anion exchange resin on styrene divinylbenzene co-polymer. The secondary microcolumn, with an internal volume of 33 µL, is packed with an extraction chromatography resin (ExCR) loaded with di-(2-ethylhexyl)phosphoric acid (HDEHP). A condition of "inverted selectivity" is presented, wherein the 89Zr elution from the primary column is synonymous with the load condition on the secondary column. The ability to transfer 89Zr from one column to the next allows two sequential purification steps to be performed prior to the final elution of the 89Zr product. This approach assures delivery of high purity 89Zr. The tandem column purification process has been implemented into a prototype automated fluidic system. Optimization of the method is presented, followed by evaluation of the process using seven cyclotron bombarded Y metal foil targets. Once optimized, we found that 93.7 ± 2.3% of the 89Zr present in the foils was recovered in the secondary column elution fraction (0.8 M oxalic acid). Radiochromatograms of the product elution peaks enabled determination of full width at half-maximum (FWHM) and 89Zr collection yields as a function of volume. Because of the small size of the secondary microcolumn, a 89Zr product volume of â¼0.28 mL is reported, which provides a substantially increased nuclide concentration over traditional methods. Finally, we evaluated the transchelation of the resulting 89Zr oxalate product to deferoxamine mesylate (DFOM) salt. We observed effective specific activities (ESA) and bindable metals concentrations ([MB]) that exceed those reported by the traditional single hydroxamate column method.
Subject(s)
Cyclotrons , Radioisotopes , Anions , Chromatography , Hydroxamic Acids/chemistry , Positron-Emission Tomography , Zirconium/chemistryABSTRACT
Most studies on surface persistence of SARS-CoV-2 have been conducted at temperatures between 20°C and 30°C. There is limited data on the survival of SARS-CoV-2 at low temperatures. In this study, the stability of SARS-CoV-2 Alpha and Delta variants on stainless steel was investigated at two temperatures (4°C and 24°C). The results show that both variants decayed more rapidly at 24°C compared with 4°C. At 24°C, Alpha and Delta variants showed reductions of 0.33 log10 and 1.02 log10, respectively, within the first 2.5 h. However, at 4°C, Alpha variant showed a reduction of 0.16 log10 within the first 2.5 h while no reduction was observed with Delta variant. After remaining in situ for 24 h at 24°C, log10 reductions of 2.66 (Alpha) and 3.11 (Delta) were observed. No viable Alpha and Delta variant was recovered after 48 h and 72 h, respectively. After 24 h in a refrigerated environment (4°C) log10 reductions of 1.16 (Alpha) and 0.95 (Delta) were observed. Under these experimental conditions, both viruses survived on stainless steel for at least 1 week. No viable Alpha and Delta variant was recovered after 10 days. These findings support the potential for increased fomite transmission of SARS-CoV-2 during winter months in colder regions worldwide and in some industrial sectors. IMPORTANCE Human transmission is believed to occur primarily through direct transfer of infectious droplets or aerosols. However, fomite transmission through contact with contaminated surfaces may also play an important role. This study provides novel evidence comparing the stability of Alpha and Delta variants on stainless steel surfaces at 4°C and 24°C. At 4°C both variants were found to be still detectable for up to 7 days. At 24°C Delta variant could be recovered over 2 days compared with Alpha variant which could not be recovered after 2 days. This has implications for fomite transmission interventions for people living and working in cold environments.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Stainless Steel , TemperatureABSTRACT
OBJECTIVE: To identify dietary patterns (DPs) characterized by a set of nutrients of concern and their association with incident type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: A total of 120,343 participants from the U.K. Biobank study with at least two 24 h dietary assessments were studied. Reduced rank regression was used to derive DPs explaining variability in energy density, free sugars, saturated fat, and fiber intakes. We investigated prospective associations with T2D using Cox proportional hazard models. RESULTS: Over 8.4 years of follow-up from the latest dietary assessment, 2,878 participants developed T2D. Two DPs were identified that jointly explained a total of 63% variation in four nutrients. DP1 was characterized by high intakes of chocolate and confectionery, butter, low-fiber bread, and sugars and preserves, and low intakes of fruits and vegetables. DP1 was linearly associated with T2D in multivariable models without BMI adjustment (per z score, hazard ratio [HR] 1.11 [95% CI 1.08-1.14]) and after BMI adjustment (HR 1.09 [95% CI 1.06-1.12]). DP2 was characterized by high intakes of sugar-sweetened beverages, fruit juice, table sugars and preserves, and low intakes of high-fat cheese and butter, but showed no clear association with T2D. There were significant interactions between both DPs and age, with increased risks among younger people in DP1 (HR 1.13 [95% CI 1.09-1.18]) and DP2 (HR 1.10 [95% CI 1.05-1.15]), as well as with DP1 and BMI, with increased risks among people with obesity (HR 1.11 [95% CI 1.07-1.16]). CONCLUSIONS: A DP characterized by high intakes of chocolate and confectionery, butter, low-fiber bread, and added sugars, and low in fresh fruits and vegetables intake is associated with a higher incidence of T2D, particularly among younger people and those with obesity.
Subject(s)
Diabetes Mellitus, Type 2 , Biological Specimen Banks , Butter , Diabetes Mellitus, Type 2/complications , Diet , Dietary Fiber , Humans , Obesity/epidemiology , Prospective Studies , Sugars , United Kingdom/epidemiologyABSTRACT
Learning collaboratives (LCs) are a popular tool for supporting collaboration and shared learning among health programs. Many variations of LCs have been reported in the literature. However, descriptions of key LC components and implementation lack standardization, making it hard to compare and contrast different LC approaches. To advance the field's understanding of how primary elements of LCs are implemented, we describe the implementation of an LC in the Ryan White HIV/AIDS Program using a recently established taxonomy of four primary elements of LCs-innovation, social systems, communication, and time. Additionally, we explain the strengths and challenges we encountered with regard to each of these elements when implementing this LC. We then offer recommendations to others on how to leverage LC facilitators and mitigate challenges in future projects. This information can guide other programs to replicate beneficial practices and avoid pitfalls in future LC projects.
Subject(s)
HIV Infections , Learning , Humans , Communication , HIV Infections/prevention & controlABSTRACT
(1) Objective: To investigate the analgesic effects of intravenous acetaminophen after intravenous administration in dogs presenting for ovariohysterectomy. (2) Methods: 14 ASA I client-owned female entire dogs. In this randomized, blinded, clinical study, dogs were given meperidine and acepromazine intramuscularly before induction of anesthesia with intravenous propofol. Anesthesia was maintained with isoflurane in oxygen. Intravenous acetaminophen 20 mg/kg or 0.9% NaCl was administered postoperatively. Pain assessments were conducted using the Glasgow Pain Scale short form before premedication and at 10, 20, 60, 120, and 180 min post-extubation or until rescue analgesia was given. The pain scores, times, and incidences of rescue analgesia between the groups was compared. Blood was collected before and 2, 5, 10, 20, 40, and 80 min after acetaminophen administration. Acetaminophen plasma concentration was quantified by liquid chromatography-mass spectrometry. The acetaminophen plasma concentration at the time of each pain score evaluation was subsequently calculated. (3) Results: There was no significant difference in pain scores at 10 min, highest pain scores, or time of rescue analgesia between groups. In each group, 3 dogs (43%) received rescue analgesia within 20 min. (4) Conclusions: Following ovariohysterectomy in dogs, there was no detectable analgesic effect of a 20 mg/kg dosage of intravenous acetaminophen administered at the end of surgery.