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1.
Appetite ; 195: 107238, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38331100

RESUMO

BACKGROUND: Many children consume a poor quality diet with only a third of children aged 6-9 years eating vegetables daily. A high quality diet is important for good health in childhood; however, the prevalence of children living with obesity has doubled from 10% to 23% during primary school in the UK. Cooking lessons have the potential to improve diet quality and reduce obesity prevalence in childhood, both of which are associated with improved cardiometabolic outcomes in adulthood. The aim of this systematic review is to investigate the impact of school-based cooking classes on cooking skills, food literacy and vegetable intake of children aged 4-12 years. METHODS: We conducted a systematic review of OVID Medline, OVID Embase, EBSCO CINHAL and EBSCO ERIC for comparative studies that evaluated outcomes of children receiving cooking classes compared to a control group. Interventions included contained food preparation or a cooking activities and took place on school premises. Risk of bias was assessed using ROB2 and Robins-I. Outcomes were pooled in a meta-analysis using a random-effects model using standardised mean differences or reviewed using narrative synthesis. Certainty of evidence was assessed using GRADE. RESULTS: We included 21 studies, (6 randomised). Meta-analysis showed a small positive effect on cooking self-efficacy of 0.39 units (95% CI 0.05 to 0.54), and a small positive effect on vegetable intake of 0.25 units (95% CI 0.05 to 0.45). Programmes with more than 6 h of cooking showed the greatest effects. CONCLUSIONS: Children's cooking programmes result in small improvements in cooking efficacy and vegetable intake, particularly those with more than 6 h of classes. It is recommended that future interventions use consistent measurement for children's food literacy and cooking confidence.


Assuntos
Culinária , Letramento em Saúde , Instituições Acadêmicas , Verduras , Humanos , Culinária/métodos , Pré-Escolar , Criança , Feminino , Masculino , Dieta , Dieta Saudável/psicologia , Comportamento Alimentar/psicologia , Obesidade Infantil/prevenção & controle
2.
BMC Med ; 21(1): 278, 2023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37501206

RESUMO

BACKGROUND: Meat-free diets may be associated with a higher risk of hip fracture, but prospective evidence is limited. We aimed to investigate the risk of hip fracture in occasional meat-eaters, pescatarians, and vegetarians compared to regular meat-eaters in the UK Biobank, and to explore the role of potential mediators of any observed risk differences. METHODS: Middle-aged UK adults were classified as regular meat-eaters (n = 258,765), occasional meat-eaters (n = 137,954), pescatarians (n = 9557), or vegetarians (n = 7638) based on dietary and lifestyle information at recruitment (2006-2010). Incident hip fractures were identified by record linkage to Hospital Episode Statistics up to September 2021. Multivariable Cox regression models were used to estimate associations between each diet group and hip fracture risk, with regular meat-eaters as the reference group, over a median follow-up time of 12.5 years. RESULTS: Among 413,914 women, 3503 hip fractures were observed. After adjustment for confounders, vegetarians (HR (95% CI): 1.50 (1.18, 1.91)) but not occasional meat-eaters (0.99 (0.93, 1.07)) or pescatarians (1.08 (0.86, 1.35)) had a greater risk of hip fracture than regular meat-eaters. This is equivalent to an adjusted absolute risk difference of 3.2 (1.2, 5.8) more hip fractures per 1000 people over 10 years in vegetarians. There was limited evidence of effect modification by BMI on hip fracture risk across diet groups (pinteraction = 0.08), and no clear evidence of effect modification by age or sex (pinteraction = 0.9 and 0.3, respectively). Mediation analyses suggest that BMI explained 28% of the observed risk difference between vegetarians and regular meat-eaters (95% CI: 1.1%, 69.8%). DISCUSSION: Vegetarian men and women had a higher risk of hip fracture than regular meat-eaters, and this was partly explained by their lower BMI. Ensuring adequate nutrient intake and weight management are therefore particularly important in vegetarians in the context of hip fracture prevention. TRIAL REGISTRATION: NCT05554549, registered retrospectively.


Assuntos
Dieta Vegetariana , Fraturas do Quadril , Adulto , Pessoa de Meia-Idade , Masculino , Humanos , Feminino , Dieta Vegetariana/efeitos adversos , Estudos Prospectivos , Bancos de Espécimes Biológicos , Estudos Retrospectivos , Vegetarianos , Dieta/efeitos adversos , Fraturas do Quadril/epidemiologia , Reino Unido/epidemiologia
3.
BMC Med ; 20(1): 275, 2022 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-35948956

RESUMO

BACKGROUND: The risk of hip fracture in women on plant-based diets is unclear. We aimed to investigate the risk of hip fracture in occasional meat-eaters, pescatarians, and vegetarians compared to regular meat-eaters in the UK Women's Cohort Study and to determine if potential associations between each diet group and hip fracture risk are modified by body mass index (BMI). METHODS: UK women, ages 35-69 years, were classified as regular meat-eaters (≥ 5 servings/week), occasional meat-eaters (< 5 servings/week), pescatarian (ate fish but not meat), or vegetarian (ate neither meat nor fish) based on a validated 217-item food frequency questionnaire completed in 1995-1998. Incident hip fractures were identified via linkage to Hospital Episode Statistics up to March 2019. Cox regression models were used to estimate the associations between each diet group and hip fracture risk over a median follow-up time of 22.3 years. RESULTS: Amongst 26,318 women, 822 hip fracture cases were observed (556,331 person-years). After adjustment for confounders, vegetarians (HR (95% CI) 1.33 (1.03, 1.71)) but not occasional meat-eaters (1.00 (0.85, 1.18)) or pescatarians (0.97 (0.75, 1.26)) had a greater risk of hip fracture than regular meat-eaters. There was no clear evidence of effect modification by BMI in any diet group (p-interaction = 0.3). CONCLUSIONS: Vegetarian women were at a higher risk of hip fracture compared to regular meat-eaters. Further research is needed to confirm this in men and non-European populations and to identify factors responsible for the observed risk difference. Further research exploring the role of BMI and nutrients abundant in animal-sourced foods is recommended. TRIAL REGISTRATION: ClinicalTrials.gov , NCT05081466.


Assuntos
Dieta Vegetariana , Fraturas do Quadril , Animais , Estudos de Coortes , Dieta/efeitos adversos , Dieta Vegetariana/efeitos adversos , Feminino , Fraturas do Quadril/epidemiologia , Humanos , Reino Unido/epidemiologia , Vegetarianos
4.
J Dairy Sci ; 105(1): 453-467, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34696913

RESUMO

Separation of the cow and calf shortly after birth is a common practice on commercial dairy farms around the world, but there are emerging concerns about this practice among citizens and other stakeholders. Continuous improvement of on-farm management practices in collaboration with dairy sector stakeholders increases the likelihood that farming systems evolve in a way that is consistent with societal expectations. Few commercial dairy farms provide extended cow-calf contact, and there is little understanding of how dairy farmers view this practice. This study examined the views of New Zealand dairy farmers toward providing cow-calf contact, particularly the barriers to adopting such a system in a seasonal-calving pasture-based dairy system. Standard farm practice in New Zealand is to remove the calf from the cow around 24 h (but could be up to 48 h) after birth. These conventional farmers (n = 63) were randomly selected from the database of all dairy farmers in New Zealand and telephone-interviewed using a semistructured interview format. Their responses to questions about providing cow-calf contact (defined as contact beyond the standard practice of 48 h) were analyzed using thematic analysis. Three major themes of concern were identified by these farmers about providing cow-calf contact as follows: (1) poor animal welfare, especially the risk of mastitis in the dam, inadequate colostrum for the calf, increased stress from delayed separation, and lack of shelter for calves while outdoors with the cow; (2) increased labor and stress on staff; and (3) system-level changes required, including infrastructure and herd management. Many of these concerns stemmed from challenges related to the nature of large-scale seasonal-calving pasture-based dairy systems, where a large number of calves are born in a short period of time and may be exposed to inclement weather in late winter in some areas. Several small-scale farmers (n = 4) providing cow-calf contact for longer than standard practice of 48 h were also interviewed; all permitted contact for at least 4 wk. These farmers also felt that animal welfare and health were important, and that this was promoted in their cow-calf contact systems. Concerns about colostrum and mastitis, for example, were not raised by these farmers, but they did agree that additional infrastructure and shelter were important considerations for cow-calf contact systems. Some conventional farmers expressed cognitive dissonance in that they theoretically preferred cow-calf contact but could not see it being realistic or practical to implement. Farmers currently providing longer cow-calf contact may be a useful resource for better understanding of how practical and economical cow-calf contact systems could be adopted on commercial pastoral dairy farms.


Assuntos
Indústria de Laticínios , Fazendeiros , Bem-Estar do Animal , Animais , Bovinos , Fazendas , Feminino , Humanos , Nova Zelândia , Gravidez
5.
J Comput Aided Mol Des ; 34(7): 783-803, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32112286

RESUMO

Reaction-based de novo design refers to the in-silico generation of novel chemical structures by combining reagents using structural transformations derived from known reactions. The driver for using reaction-based transformations is to increase the likelihood of the designed molecules being synthetically accessible. We have previously described a reaction-based de novo design method based on reaction vectors which are transformation rules that are encoded automatically from reaction databases. A limitation of reaction vectors is that they account for structural changes that occur at the core of a reaction only, and they do not consider the presence of competing functionalities that can compromise the reaction outcome. Here, we present the development of a Reaction Class Recommender to enhance the reaction vector framework. The recommender is intended to be used as a filter on the reaction vectors that are applied during de novo design to reduce the combinatorial explosion of in-silico molecules produced while limiting the generated structures to those which are most likely to be synthesisable. The recommender has been validated using an external data set extracted from the recent medicinal chemistry literature and in two simulated de novo design experiments. Results suggest that the use of the recommender drastically reduces the number of solutions explored by the algorithm while preserving the chance of finding relevant solutions and increasing the global synthetic accessibility of the designed molecules.


Assuntos
Desenho de Fármacos , Algoritmos , Técnicas de Química Sintética/métodos , Técnicas de Química Sintética/estatística & dados numéricos , Química Farmacêutica/métodos , Química Farmacêutica/estatística & dados numéricos , Simulação por Computador , Desenho Assistido por Computador , Bases de Dados de Compostos Químicos , Bases de Dados de Produtos Farmacêuticos , Humanos , Aprendizado de Máquina , Bibliotecas de Moléculas Pequenas
6.
J Chem Inf Model ; 59(10): 4167-4187, 2019 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-31529948

RESUMO

Reaction classification has often been considered an important task for many different applications, and has traditionally been accomplished using hand-coded rule-based approaches. However, the availability of large collections of reactions enables data-driven approaches to be developed. We present the development and validation of a 336-class machine learning-based classification model integrated within a Conformal Prediction (CP) framework to associate reaction class predictions with confidence estimations. We also propose a data-driven approach for "dynamic" reaction fingerprinting to maximize the effectiveness of reaction encoding, as well as developing a novel reaction classification system that organizes labels into four hierarchical levels (SHREC: Sheffield Hierarchical REaction Classification). We show that the performance of the CP augmented model can be improved by defining confidence thresholds to detect predictions that are less likely to be false. For example, the external validation of the model reports 95% of predictions as correct by filtering out less than 15% of the uncertain classifications. The application of the model is demonstrated by classifying two reaction data sets: one extracted from an industrial ELN and the other from the medicinal chemistry literature. We show how confidence estimations and class compositions across different levels of information can be used to gain immediate insights on the nature of reaction collections and hidden relationships between reaction classes.


Assuntos
Química Farmacêutica , Bases de Dados de Compostos Químicos , Aprendizado de Máquina , Modelos Químicos , Estrutura Molecular
7.
Nitric Oxide ; 72: 66-74, 2018 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-29223585

RESUMO

Inorganic nitrate (NO3-) supplementation has been shown to improve cardiovascular health indices in healthy adults. The purpose of this study was to investigate how the vehicle of NO3- administration can influence NO3- metabolism and the subsequent blood pressure response. Ten healthy males consumed an acute equimolar dose of NO3- (∼5.76 mmol) in the form of a concentrated beetroot juice drink (BR; 55 mL), a non-concentrated beetroot juice drink (BL; 456 mL) and a solid beetroot flapjack (BF; 60 g). A drink containing soluble beetroot crystals (BC; ∼1.40 mmol NO3-) and a control drink (CON; 70 mL deionised water) were also ingested. BP and plasma, salivary and urinary [NO3-] and [NO2-] were determined before and up to 24 h after ingestion. All NO3--rich vehicles elevated plasma, salivary and urinary nitric oxide metabolites compared with baseline and CON (P<0.05). The peak increases in plasma [NO2-] were greater in BF (371 ± 136 nM) and BR (369 ± 167 nM) compared to BL (283 ± 93 nM; all P<0.05) and BC (232 ± 51 nM). BR, but not BF, BL and BC, reduced systolic (∼5 mmHg) and mean arterial pressure (∼3-4 mmHg; P<0.05), whereas BF reduced diastolic BP (∼4 mmHg; P < 0.05). Although plasma [NO2-] was elevated in all conditions, the consumption of a small, concentrated NO3--rich fluid (BR) was the most effective means of reducing BP. These findings have implications for the use of dietary NO3-supplements when the main objective is to maintain or improve indices of cardiovascular health.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Nitratos/administração & dosagem , Nitratos/metabolismo , Adulto , Beta vulgaris , Suplementos Nutricionais , Sucos de Frutas e Vegetais , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Nitratos/farmacocinética , Nitritos/análise , Nitritos/metabolismo , Saliva/química
9.
10.
Nutr Rev ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916939

RESUMO

CONTEXT: Oral health and food oral-processing issues emerge with functional decline in the older adult population, potentially increasing the risk of malnutrition. Impairment of oral health is associated with poorer nutrition status; however, the relationship between oral factors and the intake of each nutrient remains poorly understood. OBJECTIVE: The associations between different oral factors and nutrient intakes among community-dwelling older adults were investigated. DATA SOURCES: A literature search from 5 databases (Web of Science, Scopus, Cochrane Library, Ovid [MEDLINE and Embase], and CINAHL) was completed on February 1, 2022. The search was limited to peer-reviewed articles published between the years 2012 and 2022. DATA EXTRACTION: Six cross-sectional studies were included in the meta-analysis. Two authors independently completed the data extraction and summarized the study characteristics, factors adjusted for in the statistical analysis, the outcome, and summary statistics of the results. DATA ANALYSIS: Meta-analyses showed evidence of a significant association between compromised oral factors (namely, denture status, chewing ability, and the number of teeth) with lower energy (weighted mean difference [WMD], -107 kcal d-1 (95% CI, -132 to -81), protein (WMD, -5.2 g d-1; 95% CI, -6.6 to -3.8), fat (WMD, -4.6 g d-1; 95% CI, -6.7 to -2.6), carbohydrate (WMD, -8.8 g d-1; 95% CI, -13.9 to -3.7), and vitamin C intakes (WMD, -12.9 mg d-1; 95% CI, -16.6 to -9.2) in older adults. CONCLUSION: Oral health can be an indicator of compromised daily energy, protein, fat, carbohydrate, and vitamin C intakes in older adults. However, the small sample size of the studies included in this review and the heterogeneity among macronutrient studies should be considered. Because of the lack of studies covering all aspects of food oral processing (eg, salivary flow rate, tongue pressure), the associations between oral processing and nutrient intake were not thoroughly explored. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022308823.

11.
Ann Clin Transl Neurol ; 11(8): 2138-2152, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38924699

RESUMO

OBJECTIVE: To define tauopathy-associated changes in the human gray and white matter proteome. METHOD: We applied tandem mass tagged labeling and mass spectrometry, consensus, and ratio weighted gene correlation network analysis (WGCNA) to gray and white matter sampled from postmortem human dorsolateral prefrontal cortex. The sampled tissues included control as well as Alzheimer's disease, corticobasal degeneration, progressive supranuclear palsy, frontotemporal degeneration with tau pathology, and chronic traumatic encephalopathy. RESULTS: Only eight proteins were unique to gray matter while six were unique to white matter. Comparison of the gray and white matter proteome revealed an enrichment of microglial proteins in the white matter. Consensus WGCNA sorted over 6700 protein isoforms into 46 consensus modules across the gray and white matter proteomic networks. Consensus network modules demonstrated unique and shared disease-associated microglial and endothelial protein changes. Ratio WGCNA sorted over 6500 protein ratios (white:gray) into 33 modules. Modules associated with mitochondrial proteins and processes demonstrated higher white:gray ratios in diseased tissues relative to control, driven by mitochondrial protein downregulation in gray and upregulation in white. INTERPRETATION: The dataset is a valuable resource for understanding proteomic changes in human tauopathy gray and white matter. The identification of unique and shared disease-associated changes across gray and white matter emphasizes the utility of examining both tissue types. Future studies of microglial, endothelial, and mitochondrial changes in white matter may provide novel insights into tauopathy-associated changes in human brain.


Assuntos
Substância Cinzenta , Proteômica , Tauopatias , Substância Branca , Humanos , Tauopatias/patologia , Tauopatias/metabolismo , Substância Branca/patologia , Substância Branca/metabolismo , Substância Cinzenta/metabolismo , Substância Cinzenta/patologia , Idoso , Feminino , Masculino , Paralisia Supranuclear Progressiva/patologia , Paralisia Supranuclear Progressiva/metabolismo , Pessoa de Meia-Idade , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , Proteoma/metabolismo
12.
Mol Inform ; 43(4): e202300183, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38258328

RESUMO

De novo design has been a hotly pursued topic for many years. Most recent developments have involved the use of deep learning methods for generative molecular design. Despite increasing levels of algorithmic sophistication, the design of molecules that are synthetically accessible remains a major challenge. Reaction-based de novo design takes a conceptually simpler approach and aims to address synthesisability directly by mimicking synthetic chemistry and driving structural transformations by known reactions that are applied in a stepwise manner. However, the use of a small number of hand-coded transformations restricts the chemical space that can be accessed and there are few examples in the literature where molecules and their synthetic routes have been designed and executed successfully. Here we describe the application of reaction-based de novo design to the design of synthetically accessible and biologically active compounds as proof-of-concept of our reaction vector-based software. Reaction vectors are derived automatically from known reactions and allow access to a wide region of synthetically accessible chemical space. The design was aimed at producing molecules that are active against PARP1 and which have improved brain penetration properties compared to existing PARP1 inhibitors. We synthesised a selection of the designed molecules according to the provided synthetic routes and tested them experimentally. The results demonstrate that reaction vectors can be applied to the design of novel molecules of biological relevance that are also synthetically accessible.


Assuntos
Desenho de Fármacos , Inibidores de Poli(ADP-Ribose) Polimerases , Inibidores de Poli(ADP-Ribose) Polimerases/química , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/síntese química , Humanos , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Poli(ADP-Ribose) Polimerase-1/metabolismo , Software
13.
Nutrients ; 15(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36678261

RESUMO

Background & aims: Iodine is important for thyroid function during pregnancy to support fetal growth, but studies of maternal iodine status and birth outcomes are conflicting. We aimed to quantify the association between iodine status and birth outcomes, including potential threshold effects using nonlinear dose−response curves. Methods: We systematically searched Medline and Embase to 10 October 2022 for relevant cohort studies. We conducted random-effects meta-analyses of urinary iodine concentration (UIC), iodine:creatinine ratio (I:Cr), and iodide intake for associations with birth weight, birth weight centile, small for gestational age (SGA), preterm delivery, and other birth outcomes. Study quality was assessed using the Newcastle-Ottawa scale. Results: Meta-analyses were conducted on 23 cohorts with 42269 participants. Birth weight was similar between UIC ≥ 150 µg/L and <150 µg/L (difference = 30 g, 95% CI −22 to 83, p = 0.3, n = 13, I2 = 89%) with no evidence of linear trend (4 g per 50 µg/L, −3 to 10, p = 0.2, n = 12, I2 = 80%). I:Cr was similar, but with nonlinear trend suggesting I:Cr up to 200 µg/g associated with increasing birthweight (p = 0.02, n = 5). Birthweight was 2.0 centiles (0.3 to 3.7, p = 0.02, n = 4, I2 = 0%) higher with UIC ≥ 150 µg/g, but not for I:Cr. UIC ≥ 150 µg/L was associated with lower risk of SGA (RR = 0.85, 0.75 to 0.96, p = 0.01, n = 13, I2 = 0%), but not with I:Cr. Conclusions: The main risk of bias was adjustment for confounding, with variation in urine sample collection and exposure definition. There were modest-sized associations between some measures of iodine status, birth weight, birth weight centile, and SGA. In pregnancy, we recommend that future studies report standardised measures of birth weight that take account of gestational age, such as birth weight centile and SGA. Whilst associations were modest-sized, we recommend maintaining iodine sufficiency in the population, especially for women of childbearing age on restricted diets low in iodide.


Assuntos
Iodo , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Gravidez , Peso ao Nascer/fisiologia , Desenvolvimento Fetal , Retardo do Crescimento Fetal , Iodetos , Iodo/urina , Parto , Nascimento Prematuro/epidemiologia
14.
Bone Rep ; 19: 101684, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38163013

RESUMO

Falls and osteoporotic fractures are a major public health problem, particularly among older adults. A third of individuals aged 65 years and over fall at least once each year, with up to 20 % of these resulting in serious injury, including fracture. In conjunction with regular exercise, the importance of diet for musculoskeletal health has largely focused upon calcium, vitamin D, and protein, particularly in the context of preventing falls and fractures. Whilst there is evidence for the benefits of these nutrients for musculoskeletal health, other aspects of the diet remain largely underexplored. For example, vegetables are rich sources of macro- and micronutrients that are essential for muscle function and bone health, which are key factors in the prevention of falls and fractures. Recent work has highlighted the importance of nutrients such as vegetable-derived nitrate and vitamin K1 in optimising muscle strength, physical function, and bone quality. In the context of dietary patterns, vegan/plant-based diets have recently gained popularity due to perceived health benefits, animal welfare, or to tackle climate change. The elimination and/or substitution of animal-based products for plant foods (without careful planning and/or expert dietary guidance) could, however, have long-term negative musculoskeletal consequences; a trend uncovered by recent evidence. Within the overarching theme of nutrition for fall and fracture prevention in older populations, the aim of this review is to (i) summarise the current evidence for calcium, vitamin D and protein; (ii) describe the importance of vegetables and selected nutrients, such as nitrate and vitamin K1, for muscle function and bone structural integrity; and (iii) highlight current evidence around different dietary patterns (e.g., plant-based, diet quality, data driven approaches) and their impact on musculoskeletal health.

15.
Clin Nutr ; 41(12): 2825-2832, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36402009

RESUMO

BACKGROUND AND AIMS: Hip fracture affects 1.6 million people globally each year, and increases morbidity and mortality. There is potential for risk reduction through diet modification, but prospective evidence for associations between intake of several foods and nutrients and hip fracture risk is limited. This study aimed to investigate associations between food and nutrient intakes and hip fracture risk in the UK Women's Cohort Study, and to determine the role of body mass index (BMI) as a potential effect modifier. METHODS: Dietary, lifestyle, anthropometric, and socio-economic information of UK women, ages 35-69 years, were collected in a survey at recruitment (1995-1998), and included a validated 217-item food frequency questionnaire. Hip fracture cases were identified by linking participant data at recruitment with their Hospital Episode Statistics (HES) up to March 2019. Cox regression models were used to estimate associations between standard portions of food and nutrient intakes and hip fracture risk over a median follow-up time of 22.3 years. RESULTS: Among 26,318 women linked to HES data (556,331 person-years), 822 hip fracture cases were identified. After adjustment for confounders, every additional cup of tea or coffee per day was associated with a 4% lower risk of hip fracture (HR (95% CI): 0.96 (0.92, 1.00)). A 25 g/day increment of dietary protein intake was also associated with a 14% lower risk of hip fracture (0.86 (0.73, 1.00)). In subgroup analyses, BMI modified linear associations between dietary intakes of protein, calcium, total dairy, milk, and tea and hip fracture risk (pinteraction = 0.02, 0.002, 0.003, 0.001, and 0.003, respectively); these foods and nutrients were associated with a reduced risk of hip fracture in underweight but not healthy or overweight participants. In particular, risk of hip fracture in underweight participants (28 cases, 545 participants) was 45% lower for every 25 g/day protein consumed (0.55 (0.38, 0.78)). CONCLUSIONS: This is the first prospective cohort study internationally of multiple food and nutrient intakes in relation to hip fracture risk by BMI using linkage to hospital records. Results suggest that the potential roles of some foods and nutrients in hip fracture prevention, particularly protein, tea and coffee in underweight women, merit confirmation. PROTOCOL REGISTRATION: Clinicaltrials.gov NCT05081466.


Assuntos
Fraturas do Quadril , Magreza , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Café , Estudos de Coortes , Proteínas Alimentares , Fraturas do Quadril/epidemiologia , Nutrientes , Estudos Prospectivos , Chá
16.
Neurobiol Aging ; 112: 55-73, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35051675

RESUMO

To understand how glia may be altered in frontotemporal degeneration with tau pathology (FTD-tau), we used a NanoString glial profiling panel to measure 770 transcripts related to glial biology in human control (n = 8), Alzheimer's disease (AD) (n = 8), and FTD-tau (n = 8) dorsolateral prefrontal cortex. Compared to control, 43 genes were upregulated and 86 genes were downregulated in the FTD-tau samples. Only 3 genes were upregulated and 2 were downregulated in AD. Pathway analysis revealed many astrocyte-, microglia-, and oligodendrocyte-related pathway scores increased in FTD-tau, while neuron-related pathway scores decreased. We compared these results to a previously published proteomic dataset containing many of the same samples and found that the targeted panel approach obtained measurements for genes whose proteins were not measured in the proteomics. Our results point to the utility of multiomic approaches and marked dysregulation of glia in FTD-tau.


Assuntos
Doença de Alzheimer , Demência Frontotemporal , Tauopatias , Doença de Alzheimer/patologia , Astrócitos/metabolismo , Encéfalo/metabolismo , Demência Frontotemporal/patologia , Humanos , Neuroglia/patologia , Proteômica , Tauopatias/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo
17.
Mol Inform ; 41(4): e2100207, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34750989

RESUMO

Reaction-based de novo design refers to the generation of synthetically accessible molecules using transformation rules extracted from known reactions in the literature. In this context, we have previously described the extraction of reaction vectors from a reactions database and their coupling with a structure generation algorithm for the generation of novel molecules from a starting material. An issue when designing molecules from a starting material is the combinatorial explosion of possible product molecules that can be generated, especially for multistep syntheses. Here, we present the development of RENATE, a reaction-based de novo design tool, which is based on a pseudo-retrosynthetic fragmentation of a reference ligand and an inside-out approach to de novo design. The reference ligand is fragmented; each fragment is used to search for similar fragments as building blocks; the building blocks are combined into products using reaction vectors; and a synthetic route is suggested for each product molecule. The RENATE methodology is presented followed by a retrospective validation to recreate a set of approved drugs. Results show that RENATE can generate very similar or even identical structures to the corresponding input drugs, hence validating the fragmentation, search, and design heuristics implemented in the tool.


Assuntos
Algoritmos , Ligantes , Estudos Retrospectivos
18.
J Sports Sci ; 29(7): 749-60, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21416448

RESUMO

Modern-day cricket has experienced a shift towards limited over games, where the emphasis is on scoring runs at a rapid rate. Although the use of protective equipment in cricket is mandatory, players perceive that leg guards, in particular, can restrict their motion. The aim of this study was to determine the influence of cricket leg guards on running performance. Initial testing revealed that wearing pads significantly increased the total time taken to complete three runs by up to 0.5 s compared with running without pads (P < 0.05). In addition, we found that the degree of impedance was dependent on pad design and could not be solely attributed to additional weight. To assess possible causes of reduced running performance, a biomechanical analysis was performed, investigating running kinematics, stride parameters, and ground reaction forces. The results revealed that the widest pad had the greatest effect on running kinematics, increasing hip abduction and decreasing hip extension, resulting in a shortened stride length (by 0.10 m) and increased stride width (by 0.12 m) compared with running without pads. Wearing pads also significantly increased peak braking force (by up to 0.3 times body weight [BW]), braking impulse (by up to 0.012 BW · s(-1)), peak mediolateral force (by up to 0.17 BW), and mediolateral impulse (by up to 0.016 BW · s(-1)) compared with running without pads, which resulted in reduced force applied in the direction of locomotion. The consequence of this reduction in running performance is an increased risk of being run-out or a reduction in the number of runs that could be scored from a particular shot.


Assuntos
Desempenho Atlético , Perna (Membro) , Movimento , Corrida , Equipamentos Esportivos , Esportes/fisiologia , Adulto , Fenômenos Biomecânicos , Peso Corporal , Quadril/fisiologia , Humanos , Masculino , Estresse Mecânico , Adulto Jovem
19.
PLoS One ; 16(1): e0245742, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33471865

RESUMO

Anticipatory behaviour occurs in the period before a reward or other positive event is presented and has been interpreted as an indicator of the welfare and emotional state of animals. The use of this indicator has received limited attention in dairy calves. Therefore, we investigated how anticipatory behaviour is affected by housing environment and reward quality, and if anticipatory behaviour changes when reward quality changes unexpectedly. Sixteen pairs of calves were assigned to treatments in a 2 x 2 factorial design (two housing environment and two reward quality combinations). Housing was either basic (2 m2/calf, river stone surface) or enriched (5 m2/calf, woodchip, and enrichment items), and the reward was access to either an additional basic or enriched pen. Calves were conditioned to anticipate reward pen access; anticipatory behaviour toward receiving the reward pen was measured. Signaling reward access increased the frequency of transitions between behaviours and duration of touching and looking at the signal and exit door. Basic-housed calves showed more anticipatory behaviour (increased frequency of transitions between behaviours) and decreased latency to access the reward compared to enriched-housed calves, but the reward pen quality had no effect on anticipatory behaviour. When the reward pen quality changed from enriched to basic unexpectedly, resulting in sudden reward loss, basic-housed calves decreased, while enriched-housed calves increased, anticipatory behaviour. However, there was no change in anticipatory behaviour during reward gain (change from basic to enriched reward pen). Our findings align with previous work showing that animals in basic housing show more anticipation for a reward, and demonstrate suppressed behavioural response when experiencing reward loss, suggesting greater sensitivity to reward. Sensitivity to reward has associations with mood state; thus, calves in basic environments may experience a more negative emotional state, and thus reduced welfare, compared to calves in enriched environments.


Assuntos
Antecipação Psicológica , Comportamento Animal , Bovinos/psicologia , Abrigo para Animais , Bem-Estar do Animal , Animais , Bovinos/fisiologia , Indústria de Laticínios/normas , Feminino , Masculino , Recompensa
20.
PLoS One ; 16(11): e0259144, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34758048

RESUMO

AIM: To summarise the totality of evidence regarding dietary risk factors for hip fracture in adults, evaluating the quality of evidence, to provide recommendations for practice and further research. DESIGN: Systematic review of meta-analyses of prospective cohort studies. ELIGIBILITY CRITERIA: Systematic reviews with meta-analyses reporting summary risk estimates for associations between hip fracture incidence and dietary exposures including oral intake of a food, food group, beverage, or nutrient, or adherence to dietary patterns. INFORMATION SOURCES: Medline, Embase, Web of Science, and the Cochrane Library from inception until November 2020. DATA SYNTHESIS: The methodological quality of systematic reviews and meta-analyses was assessed using AMSTAR-2, and the quality of evidence for each association was assessed using GRADE. Results were synthesised descriptively. RESULTS: Sixteen systematic reviews were identified, covering thirty-four exposures, including dietary patterns (n = 2 meta-analyses), foods, food groups, or beverages (n = 16), macronutrients (n = 3), and micronutrients (n = 13). Identified meta-analyses included 6,282 to 3,730,424 participants with between 322 and 26,168 hip fractures. The methodological quality (AMSTAR-2) of all systematic reviews was low or critically low. The quality of evidence (GRADE) was low for an inverse association between hip fracture incidence and intake of fruits and vegetables combined (adjusted summary relative risk for higher vs lower intakes: 0.92 [95% confidence interval: 0.87 to 0.98]), and very low for the remaining thirty-three exposures. CONCLUSION: Dietary factors may play a role in the primary prevention of hip fracture, but the methodological quality of systematic reviews and meta-analyses was below international standards, and there was a lack of high-quality evidence. More long-term cohort studies reporting absolute risks and robust, well-conducted meta-analyses with dose-response information are needed before policy guidelines can be formed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020226190.


Assuntos
Fraturas do Quadril/patologia , Bebidas/análise , Dieta , Humanos , Nutrientes/análise , Valor Nutritivo , Fatores de Risco
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