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2.
J Am Geriatr Soc ; 2024 Feb 24.
Article in English | MEDLINE | ID: mdl-38401053
3.
Appetite ; 195: 107238, 2024 04 01.
Article in English | MEDLINE | ID: mdl-38331100

ABSTRACT

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.


Subject(s)
Fruit , Vegetables , Child , Humans , Literacy , Cooking , Schools , Obesity
4.
Mol Inform ; 43(4): e202300183, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38258328

ABSTRACT

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.


Subject(s)
Drug Design , Poly(ADP-ribose) Polymerase Inhibitors , Poly(ADP-ribose) Polymerase Inhibitors/chemistry , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/chemical synthesis , Humans , Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors , Poly (ADP-Ribose) Polymerase-1/metabolism , Software
5.
BMC Med ; 21(1): 278, 2023 07 27.
Article in English | MEDLINE | ID: mdl-37501206

ABSTRACT

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.


Subject(s)
Diet, Vegetarian , Hip Fractures , Adult , Middle Aged , Male , Humans , Female , Diet, Vegetarian/adverse effects , Prospective Studies , Biological Specimen Banks , Retrospective Studies , Vegetarians , Diet/adverse effects , Hip Fractures/epidemiology , United Kingdom/epidemiology
6.
Nutrients ; 15(2)2023 Jan 12.
Article in English | MEDLINE | ID: mdl-36678261

ABSTRACT

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.


Subject(s)
Iodine , Premature Birth , Female , Humans , Infant, Newborn , Pregnancy , Birth Weight/physiology , Fetal Development , Fetal Growth Retardation , Iodides , Iodine/urine , Parturition , Premature Birth/epidemiology
7.
Bone Rep ; 19: 101684, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38163013

ABSTRACT

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.

8.
Clin Nutr ; 41(12): 2825-2832, 2022 12.
Article in English | MEDLINE | ID: mdl-36402009

ABSTRACT

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.


Subject(s)
Hip Fractures , Thinness , Adult , Aged , Female , Humans , Middle Aged , Coffee , Cohort Studies , Dietary Proteins , Hip Fractures/epidemiology , Nutrients , Prospective Studies , Tea
9.
BMC Med ; 20(1): 275, 2022 08 11.
Article in English | MEDLINE | ID: mdl-35948956

ABSTRACT

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.


Subject(s)
Diet, Vegetarian , Hip Fractures , Animals , Cohort Studies , Diet/adverse effects , Diet, Vegetarian/adverse effects , Female , Hip Fractures/epidemiology , Humans , United Kingdom/epidemiology , Vegetarians
10.
Neurobiol Aging ; 112: 55-73, 2022 04.
Article in English | MEDLINE | ID: mdl-35051675

ABSTRACT

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.


Subject(s)
Alzheimer Disease , Frontotemporal Dementia , Tauopathies , Alzheimer Disease/pathology , Astrocytes/metabolism , Brain/metabolism , Frontotemporal Dementia/pathology , Humans , Neuroglia/pathology , Proteomics , Tauopathies/metabolism , tau Proteins/genetics , tau Proteins/metabolism
11.
J Dairy Sci ; 105(1): 453-467, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34696913

ABSTRACT

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.


Subject(s)
Dairying , Farmers , Animal Welfare , Animals , Cattle , Farms , Female , Humans , New Zealand , Pregnancy
12.
Mol Inform ; 41(4): e2100207, 2022 04.
Article in English | MEDLINE | ID: mdl-34750989

ABSTRACT

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.


Subject(s)
Algorithms , Ligands , Retrospective Studies
13.
PLoS One ; 16(11): e0259144, 2021.
Article in English | MEDLINE | ID: mdl-34758048

ABSTRACT

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.


Subject(s)
Hip Fractures/pathology , Beverages/analysis , Diet , Humans , Nutrients/analysis , Nutritive Value , Risk Factors
14.
Animals (Basel) ; 11(10)2021 Oct 01.
Article in English | MEDLINE | ID: mdl-34679900

ABSTRACT

Laboratory mice are commonly euthanised with carbon dioxide (CO2); however, there is ample evidence that this gas is aversive. Previous work suggests that sedation achieved via injection with benzodiazepines prior to CO2 administration could reduce aversive behaviours during euthanasia. We explored the potential of using a voluntarily ingested sedative (tiletamine-zolazepam, Zoletil®) prior to euthanasia. Male and female C57BL/6 mice were allocated into one of the five experimental groups, which differed in the dose of Zoletil: 0, 10, 20, 40, 80 or 100 mg/kg. A dose of 20 mg/kg was found to achieve mild sedation prior to euthanasia; mice which received this dose numerically reared and walked on the cage lid less, and showed ataxia, immobility and recumbency for longer than mice that received a lower dose. During euthanasia, mice that received 20 mg/kg showed fewer aversive responses to CO2. Doses of 40 to 100 mg/kg were associated with signs of moderate to severe sedation, but resulted in an incomplete intake of the sedative, which made the interpretation of the aversiveness to CO2 difficult. Voluntary oral administration of a sedative is an effective, affordable, and easy way to minimize the stress of mice to euthanasia with CO2.

15.
Animals (Basel) ; 11(10)2021 Oct 07.
Article in English | MEDLINE | ID: mdl-34679924

ABSTRACT

In pasture-based systems, cows may spend several hours away from the paddock and may also walk several kilometres to meet daily milking requirements; this could lead cows to experience time constraints for grazing, ruminating and lying time in the paddock. This study investigated how walking distance and time spent away from the paddock affected daily behavioural patterns (i.e., grazing, ruminating and lying time) and milk yield. Dairy cows were managed in three rotationally grazed groups (n = 29 cows each) on the same farm and milked twice daily. A triaxial ear tag accelerometer on each cow recorded daily duration of grazing and ruminating, and a leg-based accelerometer recorded the daily lying time, for 13 days. GPS collars on four cows per group recorded the daily walking distance and total time away from the paddock for the group. A mixed repeated measures model tested how time off-paddock and walking distance affected the daily behavioural patterns; age, breed, milk yield and maximum ambient temperature were used as covariates with group as the observational unit. A second similar model tested how these factors affected milk yield. Walking distance and time spent away from the paddock were not correlated. When daily walking distance increased (to a maximum of 4 km/d), cows spent more time grazing and less time ruminating, but lying time was not affected. This result may, in part, be related to the greater energy expenditure demands for walking longer distances and milk production. When time away from the paddock increased (to a maximum of 4 h/d), cows spent less time lying, but grazing and ruminating times were not affected. Milk yield was not affected by walking distance, but one of the groups experienced a lower milk yield when time away from the paddock was increased. This result suggests that, for some cows, lying times may be shorter when experiencing a longer time away from the paddock, which may also affect milk yield. Overall, this study indicates that paddock behaviours are associated with walking distance to the milking parlour and time spent away from the paddock. Efforts to reduce walking distance and time spent away from the paddock are likely to provide cows with greater opportunity to engage in daily behaviours in the paddock that meet their needs and maintain their milk yield.

16.
Animals (Basel) ; 11(7)2021 Jul 14.
Article in English | MEDLINE | ID: mdl-34359221

ABSTRACT

Changes to the amount and patterns of sleep stages could be a useful tool to assess the effects of stress or changes to the environment in animal welfare research. However, the gold standard method, polysomnography PSG, is difficult to use with large animals such as dairy cows. Heart rate (HR) and heart rate variability (HRV) can be used to predict sleep stages in humans and could be useful as an easier method to identify sleep stages in cows. We compared the mean HR and HRV and lying posture of dairy cows at pasture and when housed, with sleep stages identified through PSG. HR and HRV were higher when cows were moving their heads or when lying flat on their side. Overall, mean HR decreased with depth of sleep. There was more variability in time between successive heart beats during REM sleep, and more variability in time between heart beats when cows were awake and in REM sleep. These shifts in HR measures between sleep stages followed similar patterns despite differences in mean HR between the groups. Our results show that HR and HRV measures could be a promising alternative method to PSG for assessing sleep in dairy cows.

17.
Mol Neurodegener ; 16(1): 40, 2021 06 25.
Article in English | MEDLINE | ID: mdl-34172091

ABSTRACT

BACKGROUND: There is an association between repetitive head injury (RHI) and a pathologic diagnosis of chronic traumatic encephalopathy (CTE) characterized by the aggregation of proteins including tau. The underlying molecular events that cause these abnormal protein accumulations remain unclear. Here, we hypothesized that identifying the human brain proteome from serial CTE stages (CTE I-IV) would provide critical new insights into CTE pathogenesis. Brain samples from frontotemporal lobar degeneration due to microtubule associated protein tau (FTLD-MAPT) mutations were also included as a distinct tauopathy phenotype for comparison. METHODS: Isobaric tandem mass tagged labeling and mass spectrometry (TMT-MS) followed by integrated differential and co-expression analysis (i.e., weighted gene co-expression network analysis (WGCNA)) was used to define modules of highly correlated proteins associated with clinical and pathological phenotypes in control (n = 23), CTE (n = 43), and FTLD-MAPT (n = 12) post-mortem cortical tissues. We also compared these findings to network analysis of AD brain. RESULTS: We identified over 6000 unique proteins across all four CTE stages which sorted into 28 WGCNA modules. Consistent with Alzheimer's disease, specific modules demonstrated reduced neuronal protein levels, suggesting a neurodegeneration phenotype, while other modules were increased, including proteins associated with inflammation and glial cell proliferation. Notably, unique CTE-specific modules demonstrated prominent enrichment of immunoglobulins, including IGHM and IGLL5, and extracellular matrix (ECM) proteins as well as progressive protein changes with increasing CTE pathologic stage. Finally, aggregate cell subtype (i.e., neurons, microglia, astrocytes) protein abundance levels in CTE cases were similar in expression to AD, but at intermediate levels between controls and the more exaggerated phenotype of FTLD-MAPT, especially in astrocytes. CONCLUSIONS: Overall, we identified thousands of protein changes in CTE postmortem brain and demonstrated that CTE has a pattern of neurodegeneration in neuronal-synaptic and inflammation modules similar to AD. We also identified unique CTE progressive changes, including the enrichment of immunoglobulins and ECM proteins even in early CTE stages. Early and sustained changes in astrocyte modules were also observed. Overall, the prominent overlap with FTLD-MAPT cases confirmed that CTE is on the tauopathy continuum and identified CTE stage specific molecular phenotypes that provide novel insights into disease pathogenesis.


Subject(s)
Chronic Traumatic Encephalopathy/metabolism , Chronic Traumatic Encephalopathy/pathology , Proteomics/methods , Brain/metabolism , Brain/pathology , Humans , Phenotype
18.
Sci Rep ; 11(1): 10938, 2021 05 25.
Article in English | MEDLINE | ID: mdl-34035392

ABSTRACT

Sleep is important for cow health and shows promise as a tool for assessing welfare, but methods to accurately distinguish between important sleep stages are difficult and impractical to use with cattle in typical farm environments. The objective of this study was to determine if data from more easily applied non-invasive devices assessing neck muscle activity and heart rate (HR) alone could be used to differentiate between sleep stages. We developed, trained, and compared two machine learning models using neural networks and random forest algorithms to predict sleep stages from 15 variables (features) of the muscle activity and HR data collected from 12 cows in two environments. Using k-fold cross validation we compared the success of the models to the gold standard, Polysomnography (PSG). Overall, both models learned from the data and were able to accurately predict sleep stages from HR and muscle activity alone with classification accuracy in the range of similar human models. Further research is required to validate the models with a larger sample size, but the proposed methodology appears to give an accurate representation of sleep stages in cattle and could consequentially enable future sleep research into conditions affecting cow sleep and welfare.


Subject(s)
Heart Rate , Machine Learning , Models, Biological , Sleep Stages , Animals , Cattle , Myocardium , Neural Networks, Computer , Polysomnography , ROC Curve
19.
PLoS One ; 16(1): e0245742, 2021.
Article in English | MEDLINE | ID: mdl-33471865

ABSTRACT

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.


Subject(s)
Anticipation, Psychological , Behavior, Animal , Cattle/psychology , Housing, Animal , Animal Welfare , Animals , Cattle/physiology , Dairying/standards , Female , Male , Reward
20.
Animals (Basel) ; 10(12)2020 Nov 30.
Article in English | MEDLINE | ID: mdl-33266194

ABSTRACT

Isolation during calving is a common dairy cow behavior, however it has not been examined in large outdoor group settings. The provision of "hides" was monitored for its impact on calving location and cow-calf behavior. Stocking density and bedding management were either controlled (Phase 1) or managed according to farm practice (Phase 2). Hides were used for calving by 18% (Phase 1) and 22% (Phase 2) of the cows; a further 59% and 44% of cows moved into the hides after calving (Phase 1 and 2, respectively). When hides were not available, cows calved near the edges of the calving area. In Phase 2, as stocking density increased, cows tended to use the hides less. Older cows were less likely to isolate regardless of management. Cow-calf interaction with other cows and calves was lower when hides were available. There was no evidence that hides reduced incorrect matching of cows and calves by staff, however cases of "mismothering" (i.e., calves being taken by other dams) were observed. Since the majority of cows used the hides at some stage before or after calving, we suggest opportunities for seclusion should be provided in large calving groups.

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