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Derek Walcott’s Harry Dernier and Sylvia Plath’s Three Women, two little-known, midcentury radio plays, cultivate characters who sound like the speaker of a lyric poem, even as they foreground the invisible bodies behind the voices. In offering us voices that both invite and obstruct lyric reading, Plath and Walcott make manifest a tension present in all lyric poetry—between the embodied individual, on the one hand, and the lyric speaker, on the other. Harry Dernier parodies prominent instances of poetic address, dramatizing the inadequacy of the Western literary tradition in the face of a real catastrophe. Three Women invites the audience to interpret its speakers lyrically, but then undermines the possibility of such interpretation by pointing to the ways that these voices belong to specific, gendered bodies. In this way, Plath highlights the ambiguity in how the term “voice” is used in relation to lyric and, in this, shapes a critique of lyric voicing.

Aims/hypothesis Sleep, diet and exercise are fundamental to metabolic homeostasis. In this secondary analysis of a repeated measures, nutritional intervention study, we tested whether an individual’s sleep quality, duration and timing impact glycaemic response to a breakfast meal the following morning. Methods Healthy adults’ data (N = 953 [41% twins]) were analysed from the PREDICT dietary intervention trial. Participants consumed isoenergetic standardised meals over 2 weeks in the clinic and at home. Actigraphy was used to assess sleep variables (duration, efficiency, timing) and continuous glucose monitors were used to measure glycaemic variation (>8000 meals). Results Sleep variables were significantly associated with postprandial glycaemic control (2 h incremental AUC), at both between- and within-person levels. Sleep period time interacted with meal type, with a smaller effect of poor sleep on postprandial blood glucose levels when high-carbohydrate (low fat/protein) (pinteraction = 0.02) and high-fat (pinteraction = 0.03) breakfasts were consumed compared with a reference 75 g OGTT. Within-person sleep period time had a similar interaction (high carbohydrate: pinteraction = 0.001, high fat: pinteraction = 0.02). Within- and between-person sleep efficiency were significantly associated with lower postprandial blood glucose levels irrespective of meal type (both p p = 0.035 and p = 0.051, respectively). Conclusions/interpretation Poor sleep efficiency and later bedtime routines are associated with more pronounced postprandial glycaemic responses to breakfast the following morning. A person’s deviation from their usual sleep pattern was also associated with poorer postprandial glycaemic control. These findings underscore sleep as a modifiable, non-pharmacological therapeutic target for the optimal regulation of human metabolic health. Trial registrationClinicalTrials.gov NCT03479866. Graphical abstract

Supplemental Digital Content is available in the text., Rationale: PCSK9 (proprotein convertase subtilisin/kexin type 9) circulates in a free and lipoprotein-bound form, yet the functional consequence of the association between PCSK9 and HDL (high-density lipoprotein) remains unexplored. Objective: This study sought to interrogate the novel relationship between PCSK9 and HDL in humans. Methods and Results: Comparing lipoprotein and apolipoprotein profiles by nuclear magnetic resonance spectroscopy and targeted mass spectrometry measurements with PCSK9 levels in the community-based Bruneck study (n=656) revealed a positive association of plasma PCSK9 with small HDL, alongside a highly significant positive correlation between plasma levels of PCSK9 and apolipoprotein C3 (apoC3), an inhibitor of lipoprotein lipase. The latter association was replicated in an independent cohort, the SAPHIR study (Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk; n=270). Thus, PCSK9-HDL association was determined during the postprandial response in two dietary studies (n=20 participants each, 8 time points). Peak triglyceride levels coincided with an attenuation of the PCSK9-HDL association, a loss of apoC3 from HDL, and lower levels of small HDL as measured by nuclear magnetic resonance spectroscopy. Crosslinking mass spectrometry upon isolated HDL identified PCSK9 as a potential HDL-binding partner. PCSK9 association with HDL was confirmed through size-exclusion chromatography and immuno-isolation. Quantitative proteomics upon HDL isolated from patients with coronary artery disease (n=172) returned PCSK9 as a core member of the HDL proteome. Combined interrogation of the HDL proteome and lipidome revealed a distinct cluster of PCSK9, phospholipid transfer protein, clusterin, and apolipoprotein E within the HDL proteome that was altered by sex and positively correlated with sphingomyelin content. Mechanistically, HDL facilitated PCSK9-mediated low-density lipoprotein receptor degradation and reduced low-density lipoprotein uptake through the modulation of PCSK9 internalization and multimerization. Conclusions: This study reports HDL as a binder of PCSK9 and regulator of its function. The combination of -omic technologies revealed postprandial lipemia as a driver of PCSK9 and apoC3 release from HDL. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03191513; URL: https://www.isrctn.com; Unique identifier: ISRCTN20774126.

Whilst many with SARS-CoV-2 infection have mild disease, managed in the community, individuals with cardiovascular risk factors experienced often more severe acute disease, requiring hospitalisation. Increasing concern has also developed over long symptom duration in many individuals, including the majority who managed acutely in the community. Risk factors for long symptom duration, including biological variables, are still poorly defined.We examine post-illness metabolomic and gut-microbiome profiles, in community-dwelling participants with SARS-CoV-2, ranging from asymptomatic illness to Post-COVID Syndrome, and participants with prolonged non-COVID-19 illnesses. We also assess a pre-established metabolomic biomarker score for its association with illness duration.We found an atherogenic-dyslipidaemic metabolic profile, and greater biomarker scores, associated with longer illness, both in individuals with and without SARS-CoV-2 infection. We found no association between illness duration and gut microbiome in convalescence.Findings highlight the potential role of cardiometabolic dysfunction to the experience of long illness duration, including after COVID-19.

Understanding how to modulate appetite in humans is key to developing successful weight loss interventions. Here, we showed that postprandial glucose dips 2–3 h after a meal are a better predictor of postprandial self-reported hunger and subsequent energy intake than peak glucose at 0–2 h and glucose incremental area under the blood glucose curve at 0–2 h. We explore the links among postprandial glucose, appetite and subsequent energy intake in 1,070 participants from a UK exploratory and US validation cohort, who consumed 8,624 standardized meals followed by 71,715 ad libitum meals, using continuous glucose monitors to record postprandial glycaemia. For participants eating each of the standardized meals, the average postprandial glucose dip at 2–3 h relative to baseline level predicted an increase in hunger at 2–3 h (r = 0.16, P

The gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique to each individual. We performed deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals enrolled in the Personalised Responses to Dietary Composition Trial (PREDICT 1) study, whose detailed long-term diet information, as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements were available. We found many significant associations between microbes and specific nutrients, foods, food groups and general dietary indices, which were driven especially by the presence and diversity of healthy and plant-based foods. Microbial biomarkers of obesity were reproducible across external publicly available cohorts and in agreement with circulating blood metabolites that are indicators of cardiovascular disease risk. While some microbes, such as Prevotella copri and Blastocystis spp., were indicators of favorable postprandial glucose metabolism, overall microbiome composition was predictive for a large panel of cardiometabolic blood markers including fasting and postprandial glycemic, lipemic and inflammatory indices. The panel of intestinal species associated with healthy dietary habits overlapped with those associated with favorable cardiometabolic and postprandial markers, indicating that our large-scale resource can potentially stratify the gut microbiome into generalizable health levels in individuals without clinically manifest disease.

Many patients with inflammatory bowel disease experience chronic pain, even after their inflammation is controlled. This article discusses the barriers and actions required for effective pain management.

CVD is the leading cause of death worldwide and, after dementia, is the second biggest cause of death for women. In England, it accounts for one in four of all deaths. Lifestyle modifications represent the primary route both to reduce CVD risk factors and prevent CVD outcomes. Diet constitutes one of the key modifiable risk factors in the aetiology of CVD. We investigated the relationship between nine main dietary indices and a comprehensive range of CVD risk factors in 2590 women from TwinsUK. After adjustment for multiple testing, we found that the Dietary Approaches to Stop Hypertension (DASH) diet was inversely correlated with some of the most common CVD risk factors (BMI, visceral fat (VF), TAG, insulin, homoeostasis model assessment of insulin resistance (HOMA2-IR) and atherosclerotic CVD (ASCVD) risk) with PFDR ranging from 6·28 × 10−7 to 5·63 × 10−4. Similar association patterns were detected across most of the dietary indices analysed. In our post hoc investigation, to determine if any specific food groups were driving associations between the DASH score and markers of cardiometabolic risk, we found that increased BMI, VF, HOMA2-IR, ASCVD risk, insulin and TAG levels were directly correlated with red meat consumption (PFDR ranging from 4·65 × 10−9 to 7·98 × 10−3) and inversely correlated with whole-grain cereal consumption (PFDR ranging from 1·26 × 10−6 to 8·28 × 10−3). Our findings revealed that the DASH diet is associated with a more favourable CVD risk profile, suggesting that this diet may be a candidate dietary pattern to supplement current UK dietary recommendations for CVD prevention.

Background There is convincing evidence that daily whole almond consumption lowers blood LDL cholesterol concentrations, but effects on other cardiometabolic risk factors such as endothelial function and liver fat are still to be determined. Objectives We aimed to investigate whether isoenergetic substitution of whole almonds for control snacks with the macronutrient profile of average snack intakes, had any impact on markers of cardiometabolic health in adults aged 30–70 y at above-average risk of cardiovascular disease (CVD). Methods The study was a 6-wk randomized controlled, parallel-arm trial. Following a 2-wk run-in period consuming control snacks (mini-muffins), participants consumed either whole roasted almonds (n = 51) or control snacks (n = 56), providing 20% of daily estimated energy requirements. Endothelial function (flow-mediated dilation), liver fat (MRI/magnetic resonance spectroscopy), and secondary outcomes as markers of cardiometabolic disease risk were assessed at baseline and end point. Results Almonds, compared with control, increased endothelium-dependent vasodilation (mean difference 4.1%-units of measurement; 95% CI: 2.2, 5.9), but there were no differences in liver fat between groups. Plasma LDL cholesterol concentrations decreased in the almond group relative to control (mean difference −0.25 mmol/L; 95% CI: −0.45, −0.04), but there were no group differences in triglycerides, HDL cholesterol, glucose, insulin, insulin resistance, leptin, adiponectin, resistin, liver function enzymes, fetuin-A, body composition, pancreatic fat, intramyocellular lipids, fecal SCFAs, blood pressure, or 24-h heart rate variability. However, the long-phase heart rate variability parameter, very-low-frequency power, was increased during nighttime following the almond treatment compared with control (mean difference 337 ms2; 95% CI: 12, 661), indicating greater parasympathetic regulation. Conclusions Whole almonds consumed as snacks markedly improve endothelial function, in addition to lowering LDL cholesterol, in adults with above-average risk of CVD. This trial was registered at clinicaltrials.gov as NCT02907684.

Purpose This work aimed to estimate whole almond consumption in a nationally representative UK survey population and examine associations with diet quality and cardiovascular disease (CVD) risk. Methods Four-day food record data from the National Diet and Nutrition Survey (NDNS) 2008–2017 (n = 6802, age ≥ 19 year) were analyzed to investigate associations between whole almond consumption and diet quality, measured by the modified Mediterranean Diet Score (MDS) and modified Healthy Diet Score (HDS), and CVD risk markers, using survey-adjusted multivariable linear regression. Results Whole almond consumption was reported in 7.6% of the population. Median intake in whole almond consumers was 5.0 g/day (IQR 9.3). Consumers had higher diet quality scores relative to non-consumers; higher intakes of protein, total fat, monounsaturated, n-3 and n-6 polyunsaturated fats, fiber, folate, vitamin C, vitamin E, potassium, magnesium, phosphorus, and iron; and lower intakes of trans-fatty acids, total carbohydrate, sugar, and sodium. BMI and WC were lower in whole almond consumers compared to non-consumers: 25.5 kg/m2 (95% CI 24.9, 26.2) vs 26.3 kg/m2 (25.9, 26.7), and 88.0 cm (86.2, 89.8) vs 90.1 cm (89.1, 91.2), respectively. However, there were no dose-related fully adjusted significant associations between increasing almond intake (g per 1000 kcal energy intake) and lower CVD risk markers. Conclusions Almond intake is low in the UK population, but consumption was associated with better dietary quality and lower CVD risk factors. Habitual consumption of whole almonds should be encouraged as part of a healthy diet.

Highlights • Chronic pain is common in patients with mitochondrial disease. • Pain due to mitochondrial disease is primarily of neuropathic nature. • Distribution, intensity and type of pain are genetically determined., In the absence of cure, the main objectives in the management of patients with mitochondrial disease are symptom control and prevention of complications. While pain is a complicating symptom in many chronic diseases and is known to have a clear impact on quality of life, its prevalence and severity in people with mitochondrial disease is unknown. We conducted a survey of pain symptoms in patients with genetically confirmed mitochondrial disease from two UK mitochondrial disease specialist centres. The majority (66.7%) of patients had chronic pain which was primarily of neuropathic nature. Presence of pain did not significantly impact overall quality of life. The m.3243A>G MTTL1 mutation was associated with higher pain severity and increased the likelihood of neuropathic pain compared to other causative nuclear and mitochondrial gene mutations. Although previously not considered a core symptom in people with mitochondrial disease, pain is a common clinical manifestation, frequently of neuropathic nature, and influenced by genotype. Therefore, pain-related symptoms should be carefully characterised and actively managed in this patient population.

Objectives:To examine associations of tree nut snack (TNS) consumption with diet quality and cardiovascular disease (CVD) risk in UK adults from National Diet and Nutrition Survey (NDNS) 2008–2014.Design:Cross-sectional analysis using data from 4-d food diaries, blood samples and physical measurements for CVD risk markers. To estimate diet quality, modified Mediterranean Diet Score (MDS) and modified Healthy Diet Score (HDS) were applied. Associations of TNS consumption with diet quality and markers of CVD risk were investigated using survey-adjusted multivariable linear regression adjusted for sex, age, ethnicity, socio-economic and smoking status, region of residency and total energy and alcohol intake.Setting:UK free-living population.Subjects:4738 adults (≥19 years).Results:TNS consumers had higher modified MDS and HDS relative to non-consumers. TNS consumers also had lower BMI, WC, SBP and DBP and higher HDL compared to non-consumers, although a dose-related fully adjusted significant association between increasing nut intake (g per 4184 kJ/1000 kcal energy intake) and lower marker of CVD risk was only observed for SBP. TNS consumption was also associated with higher intake of total fat, mono-, n-3 and n-6 polyunsaturated fatty acids, fibre, vitamin A, thiamin, folate, vitamin C, vitamin E, potassium, magnesium, phosphorus, selenium and iron; and lower intake of saturated fatty acids, trans fatty acids, total carbohydrate, starch, free sugar, sodium and chloride.Conclusions:TNS consumers report better dietary quality and consumption was associated with lower CVD risk factors. Encouraging replacement of less healthy snacks with TNS should be encouraged as part of general dietary guidelines.

Hepatitis E is an emerging issue, with the number of confirmed cases in the UK increasing in 2009-2015, and decreasing slightly in 2016 and 2017. There is some epidemiological evidence of an association of this virus with undercooked pork and pork products. Currently, there is no standardized method for evaluating thermal stability of HEV and also a lack of a suitable assay that can distinguish between intact HEV that can cause an infection and damaged virus which is not capable of causing an infection. This has raised concerns as it is extremely difficult to extrapolate the risk from pork products in relation to cooking practices. We are seeking to address this knowledge gap, which will not only inform our risk assessment, but will also provide an indication if cooking is sufficient to inactivate the virus in foods

Prevention of falls is important to independent living and good health in older age. Circumstances of falls may vary by older person’s sociodemographic attributes, health conditions and living environment. Health Aging and Neighborhood Study (HANS) examined rates of location and activity-specific falls among 388 community-living older adults living in Central Massachusetts between 2018 and 2020. Data on falls were collected using monthly calendar, and information on falls was collected by trained staff via telephone interviews with the participants. The follow-up time ranging from 11.9 to 24.4 months. In total, 431 falls were reported, of which 97% had information on location of fall, and 95% had information on activity at time of fall. Annualized rate of any fall differed significantly by race/ethnicity. Asians had the lowest rate (0.26/year). Rate of Hispanics was approximately twice higher (0.55, p=0.04) and non-Hispanic Whites three times higher (0.84, p

High COVID-19 mortality among nursing home (NH) residents led to their prioritization for SARS-CoV-2 vaccination; most NH residents received BNT162b2 mRNA vaccination under the Emergency Use Authorization due to first to market and its availability. With NH residents’ poor initial vaccine response, the rise of NH breakthrough infections and outbreaks, characterization of the durability of immunity to inform public health policy on the need for boosting is needed. We report on humoral immunity from 2 weeks to 6-months post-vaccination in 120 NH residents and 92 ambulatory healthcare worker controls with and without pre-vaccination SARS-CoV-2 infection. Anti-spike and anti-receptor binding domain (RBD) IgG, and serum neutralization titers, were assessed using a bead-based ELISA method and pseudovirus neutralization assay. Anti-spike, anti-RBD and neutralization levels dropped more than 84% over 6 months’ time in all groups irrespective of prior SARS-CoV-2 infection. At 6 months post-vaccine, 70% of the infection-naive NH residents had neutralization titers at or below the lower limit of detection compared to 16% at 2 weeks after full vaccination. These data demonstrate a significant reduction in levels of antibody in all groups. In particular, those infection-naive NH residents had lower initial post-vaccination humoral immunity immediately and exhibited the greatest declines 6 months later. Healthcare workers, given their younger age and relative good-health, achieved higher initial antibody levels and better maintained them, yet also experienced significant declines in humoral immunity. Based on the rapid spread of the delta variant and reports of vaccine breakthrough in NH and among younger community populations, boosting NH residents may be warranted.

Decisions on whether to use pharmacologic osteoporosis therapy in skilled nursing facility residents are complex and require shared decision-making. Residents, proxies, and staff desire individualized fracture risk estimates that consider advanced age, dementia, and mobility. They want options for reducing administration burden, monitoring instructions, and periodic reassessment of risk vs. benefit.Decisions about pharmacologic osteoporosis treatment in nursing home (NH) residents with advanced age and multimorbidity are complex and should occur using shared decision-making. Our objective was to identify processes and tools to improve shared decision-making about pharmacologic osteoporosis treatment in NHs.Qualitative analysis of data collected in three NHs from residents at high fracture risk, their proxies, nursing assistants, nurses, and one nurse practitioner (n = 28). Interviews explored participants' stories, attitudes, and experiences with oral osteoporosis medication management. Framework analysis was used to identify barriers to shared decision-making regarding osteoporosis treatment in this setting.Participants wanted individualized fracture risk estimates that consider immobility, advanced age, and comorbid dementia. Residents and proxies expected nursing staff to be involved in the decision-making; nursing staff wished to be informed on the relative risks vs. benefits of medications and given monitoring instructions. Two important competing demands to address during the shared decision-making process were burdensome administration requirements and polypharmacy. Participants wanted to reassess pharmacologic treatment appropriateness over time as clinical status or goals of care change.Shared decision-making using strategies and tools identified in this analysis may move osteoporosis pharmacologic treatment in NHs and for other older adults with multimorbidity from inappropriate inertia to appropriate prescribing or appropriate inaction.

Proprotein convertase subtilisin/kexin type 9 (PCSK9), a secreted protein that regulates circulating low-density lipoprotein (LDL) through the hepatic LDL receptor degradation pathway, is the latest therapeutic target to further lower cholesterol in patients on maximal statin therapy ([1][1]).

BACKGROUND: COVID-19 vaccines show excellent efficacy in clinical trials and effectiveness in real-world data, but some people still become infected with SARS-CoV-2 after vaccination. This study aimed to identify risk factors for post-vaccination SARS-CoV-2 infection and describe the characteristics of post-vaccination illness.METHODS: This prospective, community-based, nested, case-control study used self-reported data (eg, on demographics, geographical location, health risk factors, and COVID-19 test results, symptoms, and vaccinations) from UK-based, adult (≥18 years) users of the COVID Symptom Study mobile phone app. For the risk factor analysis, cases had received a first or second dose of a COVID-19 vaccine between Dec 8, 2020, and July 4, 2021; had either a positive COVID-19 test at least 14 days after their first vaccination (but before their second; cases 1) or a positive test at least 7 days after their second vaccination (cases 2); and had no positive test before vaccination. Two control groups were selected (who also had not tested positive for SARS-CoV-2 before vaccination): users reporting a negative test at least 14 days after their first vaccination but before their second (controls 1) and users reporting a negative test at least 7 days after their second vaccination (controls 2). Controls 1 and controls 2 were matched (1:1) with cases 1 and cases 2, respectively, by the date of the post-vaccination test, health-care worker status, and sex. In the disease profile analysis, we sub-selected participants from cases 1 and cases 2 who had used the app for at least 14 consecutive days after testing positive for SARS-CoV-2 (cases 3 and cases 4, respectively). Controls 3 and controls 4 were unvaccinated participants reporting a positive SARS-CoV-2 test who had used the app for at least 14 consecutive days after the test, and were matched (1:1) with cases 3 and 4, respectively, by the date of the positive test, health-care worker status, sex, body-mass index (BMI), and age. We used univariate logistic regression models (adjusted for age, BMI, and sex) to analyse the associations between risk factors and post-vaccination infection, and the associations of individual symptoms, overall disease duration, and disease severity with vaccination status.FINDINGS: Between Dec 8, 2020, and July 4, 2021, 1 240 009 COVID Symptom Study app users reported a first vaccine dose, of whom 6030 (0·5%) subsequently tested positive for SARS-CoV-2 (cases 1), and 971 504 reported a second dose, of whom 2370 (0·2%) subsequently tested positive for SARS-CoV-2 (cases 2). In the risk factor analysis, frailty was associated with post-vaccination infection in older adults (≥60 years) after their first vaccine dose (odds ratio [OR] 1·93, 95% CI 1·50-2·48; pINTERPRETATION: To minimise SARS-CoV-2 infection, at-risk populations must be targeted in efforts to boost vaccine effectiveness and infection control measures. Our findings might support caution around relaxing physical distancing and other personal protective measures in the post-vaccination era, particularly around frail older adults and individuals living in more deprived areas, even if these individuals are vaccinated, and might have implications for strategies such as booster vaccinations.FUNDING: ZOE, the UK Government Department of Health and Social Care, the Wellcome Trust, the UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare, the UK National Institute for Health Research, the UK Medical Research Council, the British Heart Foundation, and the Alzheimer's Society.

BackgroundCOVID-19 vaccines show excellent efficacy in clinical trials and real-world data, but some people still contract SARS-CoV-2 despite vaccination. This study sought to identify risk factors associated with SARS-CoV-2 infection post-vaccination and describe characteristics of post-vaccination illness.MethodsAmongst 1,102,192 vaccinated UK adults from the COVID Symptom Study, 2394 (0.2%) cases of post-vaccination SARS-CoV-2 infection were identified between 8th December 2020 and 1st May 2021. Using a control group of vaccinated individuals testing negative, we assessed the associations of age, frailty, comorbidity, area-level deprivation and lifestyle factors with infection. Illness profile post-vaccination was assessed using a second control group of unvaccinated cases.FindingsOlder adults with frailty (OR=2.78, 95% CI=[1.98-3.89], p-valueInterpretationOur findings suggest that older individuals with frailty and those living in most deprived areas are at increased risk of infection post-vaccination. We also showed reduced symptom burden and duration in those infected post-vaccination. Efforts to boost vaccine effectiveness in at-risk populations, and to targeted infection control measures, may still be appropriate to minimise SARS-CoV-2 infection.FundingThis work is supported by UK Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre (BRC) award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust and via a grant to ZOE Global; the Wellcome Engineering and Physical Sciences Research Council (EPSRC) Centre for Medical Engineering at King’s College London (WT 203148/Z/16/Z). Investigators also received support from the Chronic Disease Research Foundation, the Medical Research Council (MRC), British Heart Foundation, the UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value Based Healthcare, the Wellcome Flagship Programme (WT213038/Z/18/Z and Alzheimer’s Society (AS-JF-17-011), and the Massachusetts Consortium on Pathogen Readiness (MassCPR).Research in contextEvidence before this studyTo identify existing evidence for risk factors and characteristics of SARS-CoV-2 infection post-vaccination, we searched PubMed for peer-reviewed articles published between December 1, 2020 and May 18, 2021 using keywords (“COVID-19” OR “SARS-CoV-2”) AND (“Vaccine” OR “vaccination”) AND (“infection”) AND (“risk factor*” OR “characteristic*”). We did not restrict our search by language or type of publication. Of 202 articles identified, we found no original studies on individual risk and protective factors for COVID-19 infection following vaccination nor on nature and duration of symptoms in vaccinated, community-based individuals. Previous studies in unvaccinated populations have shown that social and occupational factors influence risk of SARS-CoV-2infection, and that personal factors (age, male sex, multiple morbidities and frailty) increased risk for adverse outcomes in COVID-19. Phase III clinical trials have demonstrated good efficacy of BNT162b2 and ChAdOx1 vaccines against SARS-CoV-2 infection, confirmed in published real-world data, which additionally showed reduced risk of adverse outcomes including hospitalisation and death.Added value of this studyThis is the first observational study investigating characteristics of and factors associated with SARS-CoV-2 infection after COVID-19 vaccination. We found that vaccinated individuals with frailty had higher rates of infection after vaccination than those without. Adverse determinants of health such as increased social deprivation, obesity, or a less healthy diet were associated with higher likelihood of infection after vaccination. In comparison with unvaccinated individuals, those with post-vaccination infection had fewer symptoms of COVID-19, and more were entirely asymptomatic. Fewer vaccinated individuals experienced five or more symptoms, required hospitalisation, and, in the older adult group, fewer had prolonged illness duration (symptoms lasting longer than 28 days).Implications of all the available evidenceSome individuals still contract COVID-19 after vaccination and our data suggest that frail older adults and those living in more deprived areas are at higher risk. However, in most individuals illness appears less severe, with reduced need for hospitalisation and lower risk of prolonged illness duration. Our results are relevant for health policy post-vaccination and highlight the need to prioritise those most at risk, whilst also emphasising the balance between the importance of personal protective measures versus adverse effects from ongoing social restrictions. Strategies such as timely prioritisation of booster vaccination and optimised infection control could be considered for at-risk groups. Research is also needed on how to enhance the immune response to vaccination in those at higher risk.

Objectives: Animal studies support a role for the gut microbiota in hypertension development, but large human studies are lacking. Here, we investigated the relationship between hypertension prevalence and gut microbial composition in two cohorts. Methods: We included 871 unrelated TwinsUK women with faecal microbiome data (16s rRNA gene sequencing). Multivariable linear models adjusted for age, age2 and BMI as well as MiRKAT models, were used to estimate the association of hypertension with alpha- and beta-diversity metrics. To identify taxa associated with hypertension, a generalized additive model for location scale and shape was computed adjusting for covariates and multiple testing. Results were replicated in 448 women from PREDICT-1. Results: We found that measures of alpha diversity are significantly lower in hypertensive cases [Beta(95% confidence interval, 95% CI) = −0.05 (−0.095 to −0.004), P = 0.03] and a significant association between beta diversity and hypertension (FDR

The global rise in obesity and type 2 diabetes has generated significant interest in regulating the glycaemic impact of staple foods. Wheat breads (white or wholemeal) are popular staples, but have a high-glycaemic index, due to the highly digestible wheat starch. Reducing the glycaemic potency of white bread is challenging because the bread-making conditions are mostly conducive to starch gelatinisation. Cellular legume powders are a new source of type 1 resistant starch, where the starch is encapsulated by dietary fibre in the form of intact plant cell walls. The starch in these cell powders is less susceptible to gelatinisation and digestion than starch in conventional legume flours. However, legume cell resilience to baking conditions and the effects of this ingredient on glycaemic responses and product quality are unknown. Here we show that the integrity of cell wall fibre in chickpea powder was preserved on baking and this led to a ~40% reduction in in vivo glycaemic responses (iAUC120) to white bread rolls (~50 g available carbohydrate and 12 g wheat protein per serving) when 30% or 60% (w/w) of the wheat flour was replaced with intact cell powder. Significant reductions in glycaemic responses were achieved without adverse effects on bread texture, appearance or palatability. Starch digestibility analysis and microscopy confirmed the importance of cell integrity in attenuating glycaemic responses. Alternative processing methods that preserve cell integrity are a new, promising way to provide healthier low glycaemic staple foods; we anticipate that this will improve dietary options for diabetes care., Graphical abstract Image 1, Highlights • Intact cell powder (ICP): a new legume ingredient increased type 1 resistant starch in bread rolls. • ICP lowered starch bioaccessibility and glycaemic response of wheat bread rolls. • Legume cell integrity was retained after baking and digestion. • Wheat breads incorporating ICP had acceptable quality attributes.

Evidence regarding the impact of COVID-19 on health behaviours is limited. In this prospective study including 1.1 million UK and US participants we collected diet and lifestyle data ‘pre-’ and ‘peri-’ pandemic, and computed a bi-directional health behaviour disruption index. We show that disruption was higher in the younger, female and socioeconomically deprived (p

A mother of a baby boy born at 36 weeks’ gestation is declining vitamin K administration. The baby is well and has no family history. The mother says that there is not enough evidence to prove that vitamin K works and is worried about the risk of cancer. The clinician’s job is to present and weigh up the current evidence on neonatal administration of vitamin K. Vitamin K deficiency bleeding (VKDB) is a rare but potentially fatal haemostatic disorder. It manifests as bleeding at multiple sites in otherwise healthy infants.1 It occurs in the first 6 months of life and is almost entirely preventable by administration of vitamin K prophylaxis at birth. As bleeding can occur until 6 months of age, the previous term haemorrhagic disease of new-born was replaced by VKDB.2 It is subclassified according to the age of onset of bleeding; early (within the first 24 hours), classical (days 1–7) and late (week 1–6 months of age).1 Vitamin K represents a group of essential cofactors for the activation of proteins which are involved in blood coagulation, including factor II, VII, IX, X, protein C, protein S and protein Z.3 Vitamin K is necessary for the synthesis of coagulation factors in the liver.4 Babies are deficient in vitamin K at birth, therefore leading to the increased risk of bleeding. Most vitamin K in adults and children is sourced through the diet, for example, leafy green vegetables.3 Neonates acquire their vitamin K by transfer through the placenta. The rate of this transfer is extremely low.5 Preterm infants are at an even greater risk of vitamin K deficiency due to various factors, including delayed feeding and therefore delayed gastric colonisation with microflora which produce vitamin K.4 The immature …

ObjectivesDietary supplements may provide nutrients of relevance to ameliorate SARS-CoV-2 infection, although scientific evidence to support a role is lacking. We investigate whether the regular use of dietary supplements can reduce the risk of testing positive for SARS-CoV-2 infection in around 1.4M users of the COVID Symptom Study App who completed a supplement use questionnaire.DesignLongitudinal app-based community survey and nested case control study.SettingSubscribers to an app that was launched to enable self-reported information related to SARS-CoV-2 infection for use in the general population in three countries.Main ExposureSelf-reported regular dietary supplement usage since the beginning of the pandemic.Main Outcome MeasuresSARS-CoV-2 infection confirmed by viral RNA polymerase chain reaction test (RT-PCR) or serology test. A secondary outcome was new-onset anosmia.ResultsIn an analysis including 327,720 UK participants, the use of probiotics, omega-3 fatty acids, multivitamins or vitamin D was associated with a lower risk of SARS-CoV-2 infection by 14%(95%CI: [8%,19%]), 12%(95%CI: [8%,16%]), 13%(95%CI: [10%,16%]) and 9%(95%CI: [6%,12%]), respectively, after adjusting for potential confounders. No effect was observed for vitamin C, zinc or garlic supplements. When analyses were stratified by sex, age and body mass index (BMI), the protective associations for probiotics, omega-3 fatty acids, multivitamins and vitamin D were observed in females across all ages and BMI groups, but were not seen in men. The same overall pattern of association was observed in both the US and Swedish cohorts. Results were further confirmed in a sub-analysis of 993,365 regular app users who were not tested for SARS-CoV-2 with cases (n= 126,556) defined as those with new onset anosmia (the strongest COVID-19 predictor).ConclusionWe observed a modest but significant association between use of probiotics, omega-3 fatty acid, multivitamin or vitamin D supplements and lower risk of testing positive for SARS-CoV-2 in women. No clear benefits for men were observed nor any effect of vitamin C, garlic or zinc for men or women. Randomised controlled trials of selected supplements would be required to confirm these observational findings before any therapeutic recommendations can be made.

Coeliac disease (CD) is a lifelong, immune-mediated, systemic disease precipitated by exposure to dietary gluten in genetically predisposed individuals. It affects all age groups with a diverse range of clinical signs and symptoms.1 Over the past five decades, there has been a fourfold increase in the incidence of CD in the UK, which is largely due to increased disease awareness, advances in diagnostic tests and development of screening programmes. However, data from recent population-based studies suggest that at least 1 in 100 people in the UK are affected by CD, meaning approximately 70% (500 000 people) remain undiagnosed, showing further improvements need to be made.2–4 In January 2020, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) published new evidence-based guidelines for diagnosing CD in children. The 2012 ESPGHAN and the 2016 NICE guidelines on CD were used to develop 10 focused, clinical questions using the PICO (population, indicator, comparator and outcome) format.(see box 1). For each question, a thorough review of current evidence was systemically analysed, overall strength of the evidence evaluated and discussed among the workgroup for relevance and implications to clinical practice. From this, a responding recommendation was formulated, which was graded for strength according to the GRADE approach.5 Box 1 ### Questions for the 2020 European Society Paediatric Gastroenterology, Hepatology and Nutrition criteria for the diagnosis of CD5 1. Is there a difference in the prevalence of CD in children with constipation, abdominal pain, signs of IBS, dyspepsia, malabsorption, iron deficiency anaemia or oral aphthae compared with the general population? 2. What will HLA-DQ2 and DQ8 determination add to the diagnostic certainty of CD-diagnosis? 3. Does the algorithm proposed to avoid biopsies in symptomatic patients work in asymptomatic subjects? 4. Which serological test is the most appropriate to diagnose CD? 5. Should more than one serological test be used and, if so, what should the sequence of testing be? 6. At which cut-off for IgA antibodies against type-2 …

Metabolic responses to food influence diabetes risk, but data suitable for determining personalized nutritional advice are lacking. PREDICT 1 (n=1102 twins and unrelated healthy UK/U.S. adults) examined genetic, metabolic, microbiome, and meal composition/context contributions to postprandial metabolic responses in clinic and at home. This 2-week interventional trial included the administration of standardized meals/beverages and monitored of ad libitum food intake. Objective assessments of sleep and physical activity were made. Blood glucose was continuously assessed and triglycerides and C-peptide were measured repeatedly. Large and consistent differences between individuals in blood triglyceride, glucose, and insulin responses to identical meals were observed. Person-specific factors, including variation in the gut microbiome, had a greater influence than meal macronutrients; genetic variants had a modest impact on predictions. Modifiable factors such as meal timing had large effects, highlighting avenues to improve postprandial responses. As predictors of CVD risk, postprandial triglyceride and glucose improved on traditional fasting markers. Machine learning was utilized to derive personalized predictions for both triglyceride (r=0.47) and glycemic (r=0.77) responses. Disclosure P.W. Franks: Advisory Panel; Self; Zoe Global Ltd. Consultant; Self; Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk A/S, Sanofi, Servier. S. Berry: Consultant; Self; Zoe Global. A.M. Valdes: None. D.A. Drew: None. R.J. Davies: Employee; Self; Zoe Global Ltd. J. Merino: None. A.T. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Pfizer Inc. N. Segata: Consultant; Self; Zoe Global Ltd. T.D. Spector: Stock/Shareholder; Self; Zoe Global Ltd. Funding Zoe Global Ltd.; UK Wellcome Trust (212904/Z/18/Z); Medical Research Council/British Heart Foundation Ancestry and Biological Informative Markers for Stratification of Hypertension (M016560/1); European Research Council (CoG-2015_681742_NASCENT to P.W.F.); UK Wellcome Trust; Medical Research Council; European Union; Chronic Disease Research Foundation; Zoe Global Ltd.; National Institute for Health Research-funded BioResource, Clinical Research Facility and Biomedical 511 Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London

The Personalised REsponses to DIetary Composition Trial (PREDICT) was a single-arm, single-blind intervention study that utilized both standardized “test” meals and captured “free-living” non-standardized food consumption, to predict an individual’s metabolic response to foods based on the person’s characteristics (including their metabolomic and gut microbiome profiles), meal composition (macronutrients and energy content) and meal context (including time of day, sleep and exercise). The initial study commenced in June 2018 and targeted 1,000 generally healthy participants between the ages of 18 and 65 years for enrollment in the United Kingdom, and recruited from the existing and ongoing TwinsUK research cohort and the general population. In December 2018, an independent trial mirroring the UK protocol was launched in parallel at Massachusetts General Hospital to serve as a US-based validation cohort including 100 healthy individuals in the general population. The overall objective of these trials was to predict glucose, insulin, lipid and other postprandial responses to foods based on the individual’s characteristics, including molecular biomarkers and lifestyle factors as well as the nutritional composition of the food. The studies, collectively termed PREDICT 1, were completed in May 2019. The study has delivered highly-dimensional multi-omic data from which the predictors of individual postprandial responses have been determined. These findings will be used to design personalized dietary interventions focused on key health outcomes. This protocol is registered with the US National Institutes of Health trial registry, ClinicalTrials.gov: NCT03479866.

Interesterified (IE) saturated-rich fats are widely used to replace partially-hydrogenated fats as hard fats with functional properties needed for spreads/margarines, baked goods, and confectionary, while avoiding the health hazards of trans fats. However, the amount of IE fat consumed and their predicted pubic health impact relative to other application-appropriate fats is unknown. We investigated current intakes of IE fats and the dietary impact of substitution of IE with functionally-equivalent replacement fats using observational data from the UK National Diet and Nutrition Survey (NDNS) (years 5–6 (2012–2014), n = 2546) and technical manufacturing data from a UK IE fat supplier. The major sources, types and quantities of IE fat intake were calculated for the total population and different age, ethnic and socioeconomic groups.IE fat contributes 3.4% of total fat and 1.1% of % total energy intake (TEI) (range 0–10.3%), with 19–64 yr old males consuming 1.1% and females 0.9% TEI from IE fats. 19–64 yr old quartiles of TEI intake were: 0.1%, 0.5%, 1.0% and 2.2%. The 65 yr + age category consumed the most IE fat (1.5% Energy), followed by 11–18 yr (1.2%) and 19–64 yr (1.0%). TEI from IE fats was 1% for high-income households, 1.1% for the middle-income group and 1.2% for the low-income group. White individuals consumed more energy from IE fat (1.2% TEI) than all other ethnic groups (0.7% TEI).The main sources of IE fats in the UK are from retail spreads (margarines); 54.2%, baked goods; 22.1%, biscuits; 7.7%, non-dairy creams; 5.9% and confectionery; 5.6%. Palmitic/lauric acid-rich IE fats, formulated from palm and palm kernel oils, account for 70% of IE fat consumed. Reformulation of the largest contributor to IE intakes (spreads) to remove IE fat, but retain the same functional characteristics, increased the saturated fatty acid (SFA) composition from 22% to 37%, 25% to 36%, 39% to 42% in three most commonly consumed spread formulations. Replacement of IE fats with non-IE alternative formulations would increase population SFA intake by 0.3% of TEI.IE fats contribute a small but important amount to the fat intake of the UK population. Removal of IE fat would result in an increase in SFA intake which may have public health implications. Previous research has not focused on the most commonly consumed IE fat blends identified (Palmitic/lauric rich), therefore a re-prioritisation of future research work is recommended to assess the potential impact of IE fats consumed by the UK population.

Postprandial lipemia is an independent risk factor for CVD, due to effects on lipoprotein remodelling, oxidative stress, inflammation, haemostasis and endothelial dysfunction. However, it is unknown whether the total, peak or duration of the lipemic response determines risk. The PREDICT I study is the largest study to date to measure postprandial lipemic responses and intermediary acutely changing cardiometabolic risk factors at multiple time points using a standardized test meal model.A multi-center postprandial study of 1,000 individuals from the UK (unrelated, identical and non-identical twins) and 100 unrelated individuals from the US, assessed postprandial (hourly 0–6h) metabolic responses to sequential mixed-nutrient dietary challenges (50 g fat, 85 g carbohydrate at 0 h; 22 g fat, 71 g carbohydrate at 4h) in a clinic setting. We investigated the relationship of different postprandial triacylglycerol (TG) measures (4 and 6 h TG iAUC, 4 and 6 h TG concentration, 4 and 6 h TG increase from fasting) with lipoprotein remodelling (XXL-VLDL (including chylomicron remnants and VLDL particles) and XL-VLDL particle concentrations (average diameters > 75, 64 nm respectively), HDL-C) and levels of glycosylated acute phase proteins (GlycA; marker of cardiovascular inflammation), all of which have been implicated as independent predictors of CVD risk.Following adjustment (for use of medication, demographic characteristics, fasting TG, insulin and glucose levels), all six postprandial TG measures (4 and 6 h TG iAUC, 4 and 6 h TG concentration, 4 and 6 h TG increase from fasting) were strongly correlated with markers of atherogenic lipoprotein remodelling and the marker of cardiovascular inflammation (GlycA). The strongest correlation (interim analysis) was observed for the 6 h TG increase from fasting (all P < 0.001, Pearson's coefficient r = 0.94 [95%CI's; 0.93, 0.95] for XXL-VLDL-P; r = 0.95 [95%CI's; 0.95, 0.96] for XL-VLDL-P; r = 0.89 [95%CI's; 0.88, 0.91] for GlycA ; r = -0.61 [95%CI's; -0.66, -0.55] for HDL-C). Inter-individual variability in postprandial lipemic responses was high in the tightly controlled clinic setting (interim analysis, n = 656); IQR (median) was; iAUC (0–6h) 2.39 (2.31) mmol/L.h; Cmax 1.32 (2.06) mmol/L; Tmax 30.0 (300) min; and increase above fasting at 6 h 0.78 (0.62) mmol/L.This is the most detailed postprandial study performed to date and suggests that identifying predictors of the postprandial 6 h TG rise will have the highest CVD relevance. Ongoing exploration in PREDICT I of the determinants of postprandial lipemic responses considering environmental, genetic and microbiome variables will significantly advance our ability to predict an individual's postprandial response and its links to cardiovascular risk.

Interesterified (IE) fats are widely used to replace partially-hydrogenated fats as hard fats with functional and sensory properties needed for spreads/margarines, baked goods, and confectionary, while avoiding the health hazards of trans fats. Detailed mechanistic work to determine the metabolic effects of interesterification of commonly-consumed hard fats has not yet been done. Earlier studies using fats less commonly consumed have shown either neutral or a lowering effect on postprandial lipaemia. We investigated postprandial lipaemia, lipoprotein remodelling, and triacylglycerol-rich lipoprotein (TRL) fraction apolipoprotein concentrations following a common IE blend of palm oil/kernel fractions versus its non-IE counterpart, alongside a reference monounsaturated (MUFA) oil. A 3-armed, double blind, randomized controlled trial (clinicaltrials.gov NCT03191513) in healthy adults (n = 20; 10 men, 10 women) aged 45–75 y, assessed effects of single meals (897 kcal, 50 g fat, 16 g protein, 88 g carbohydrate) on postprandial plasma triacylglycerol (TAG) concentrations, lipoprotein profiles, and TRL fraction apolipoprotein B48 and TAG concentrations. Test fats were IE 80:20 palm stearin/palm kernel fat, the equivalent non-IE fat, and a high-MUFA reference oil (rapeseed oil, RO). Blood was collected at baseline and hourly for 8 h. Linear mixed modelling was performed, adjusting for treatment order and baseline values (ver. 24.0; SPSS Inc., Chicago, IL, USA). Total 8 h incremental area under the curves (iAUC) for plasma TAG concentrations were lower following IE and non-IE compared with RO (mean difference in iAUC: non-IE vs. RO -1.8 mmol/L.h (95% CI -3.3, -0.2); IE vs. RO -2.6 mmol/L.h (95% CI -5.3, 0.0)), but iAUCs for IE and non-IE were not significantly different. There were no differences between IE and non-IE for chylomicron fraction apoB48 concentrations nor TAG:apoB48 ratio. No differences were observed between IE and non-IE for lipoprotein (VLDL, HDL, LDL) particle size or sub-class particle concentrations. However, LDL particle diameters were reduced at 5 and 6 h following IE vs RO (P < 0.05). XXL- (including chylomicron remnants and VLDL particles), XL- and L-VLDL particle concentrations (average diameters > 75, 64, and 53.6 nm respectively) were higher following IE and non-IE vs. RO at 6 h (P < 0.05) and 8 h postprandially (P < 0.005–0.05). In conclusion, both IE and non-IE palmitic acid-rich fats generated a greater preponderance of pro-atherogenic large TRL remnant particles in the late postprandial phase relative to an oleic acid-rich oil. However, the process of interesterification did not modify postprandial TAG response or lipoprotein metabolism.

Endothelial dysfunction is a predictor for cardiovascular disease risk and is a key feature of atherosclerosis. Poor diet quality, including consumption of saturated fat-rich, high-refined carbohydrate snack foods, may have adverse effects on endothelial function. Thus, snack foods, which contribute an average of 20% of energy intake in the UK adult population, present an easily identifiable target to improve vascular health. Almonds are nutrient-dense foods that are rich in unsaturated fats, fibre, minerals and non-nutrient bioactives (NNB), and may have health benefits by displacing snacks high in refined carbohydrates, enriching the diet with micronutrients and NNB, and/or low lipid bioaccessibility. Human clinical trials have demonstrated LDL cholesterol-lowering effects of daily almond consumption, yet the effects on endothelial function are unclear. This study aimed to investigate whether replacing habitual snacks (20% estimated daily energy requirements) with almonds had any impact on endothelium-dependent vasodilation, measured by flow-mediated dilatation (FMD) using ultrasound imaging of the brachial artery following reactive hyperaemia. A randomised, controlled, parallel trial in adult regular snack consumers aged 30–70 y at moderate risk of cardiovascular disease was conducted, including a 2-week run-in period with control snacks and a 6-week intervention period. Control sweet and savoury mini muffin snacks were developed to replicate the average UK snack nutrient profile, which was calculated from snack foods identified in the UK National Diet and Nutrition Survey (NDNS) database (55% energy from carbohydrate, 36% total fat (14% saturated fat), and 10% protein). One hundred and nine volunteers (77 females and 32 males; mean age 56 y) were enrolled in the study and 107 were randomised to isocaloric treatments, 1) control muffins, or 2) dry roasted whole almonds; 105 participants completed the study. Almonds significantly increased FMD relative to control (mean difference 3.6%, 95% CI 1.7, 5.5; P < 0.001), indicating improved endothelial function, and LDL-cholesterol (mean difference -0.25 mmol/L, 95% CI -0.47, -0.03; P = 0.030) significantly decreased adjusted with sex, age and baseline BMI and baseline dependent outcome values. Snacking on whole almonds as a replacement for snacks high in refined starch and sugar, and low in fibre and unsaturated fatty acids, improves endothelial function. The results of this study provide further evidence for the importance of nuts in dietary strategies to reduce risk of cardiovascular disease.

Glycemic, insulinemic and lipemic postprandial responses are multi-factorial and contribute to diabetes, obesity and CVD. The aim of the PREDICT I study is to assess the genetic, metabolic, metagenomic, and meal-context contribution to postprandial responses, integrating the metabolic burden and gut microbiome to predict individual responses to food using a machine learning algorithm.A multi-center postprandial study of 1,000 individuals from the UK (unrelated, identical and non-identical twins) and 100 unrelated individuals from the US, assessed postprandial (0–6h) metabolic responses to sequential mixed-nutrient dietary challenges (50 g fat and 85 g carbohydrate at 0 h; 22 g fat and 71 g carbohydrate at 4h) in a clinic setting. Glycemic responses to 5 duplicate isocaloric meals of different macronutrient content and self-selected meals (> 100,000), were tested at home using a continuous glucose monitor (CGM). Baseline factors included metabolomics, genomics, gut metagenomics and body composition. Genetic contributions to postprandial responses were determined by classical twin methods.Inter-individual variability in postprandial responses (glucose, insulin and triacylglycerol (TG)) was high in the clinic setting: iAUC IQR (median) was (n = 644); glucose (0–2h) 1.97 (1.89) mmol/L.h, insulin (0–2h) 45.6 (67.7) mIU/L.h and TG (0–6h) 2.37 (2.42) mmol/L.h. The unadjusted genetic contribution for glucose, insulin and TG responses were 54%, 29% and 27% respectively. Within-individual concordance (ICC) in glucose responses (iAUC 0–2h) for at home duplicate isocaloric meals was moderate-to-high, depending on the test meal: ICC (95%CI) was; high carbohydrate 0.62 (0.58,0.66), (carbohydrate = 95g/76% energy; n = 764), average lunch 0.57 (0.53, 0.62) (carbohydrate = 68g/54% energy; n = 763), OGTT 0.65 (0.61,0.70) (carbohydrate = 75 g; n = 754), high fat 0.35 (0.28, 0.41) (fat = 40g/71% energy; n = 576) and high protein 0.56, (0.48,0.62) (protein = 41g/32% energy; n = 364). An interim machine learning algorithm predicted 46% of the variation in glycemic responses based on meal content, meal context and participant's baseline characteristics, excluding genetic and microbiome features. Only 29% of variation could be explained by the macronutrient content of the meal.This is the most comprehensive postprandial study performed to date. The large and modifiable variation in metabolic responses to identical meals in healthy people explains why ‘one size fits all’ nutritional guidelines are problematic. The genetic component to these responses is moderate, leaving the majority of the variation potentially modifiable. By collecting information on glucose responses to > 100,000 meals, alongside environmental, genetic and microbiome variables, we will have excellent power to use machine learning to optimise and predict individual responses to foods.

This study aimed to examine the relationship between dietary practices and sleep in young children.In this study, 2-y-old children (n = 6327) and their mothers were enrolled at birth and during pregnancy, respectively. The study obtained maternal demographic, health, and lifestyle data during late pregnancy. Parents reported the 2-y-old child's dietary practices on a food frequency questionnaire, as well as sleep duration and night-waking frequency. Measures of dietary intake quantified servings per day for each food group (grouped as low/moderate/high intake). Sleep measures were as inadequate sleep when11 h sleep in a 24-h period and increased night waking when waking ≥2 times per night. Multivariable logistic regression analyses examined associations between toddler diet and sleep, which were described using adjusted odds ratios (ORs) and 95% confidence intervals.In this study, 2-y-old children (n = 6288) slept for a mean of 12.3 hours (standard deviation: ±1.5 hours) over a 24-h period, with 734 children (12%) getting11 h of sleep in 24 h. Increased night waking occurred in 1063 children (17%). Compared with low intake, high soft drink/snack/fast food intake was associated with inadequate sleep (OR: 1.37) and increased night waking (OR: 1.34). High milk/cheese/yoghurt intake (OR: 1.55) was associated with increased odds of night waking, but moderate (OR: 0.81) or high (OR: 0.78) vegetable intake was associated with decreased odds of night waking. Exposure to screens (OR: 1.28) and heavy maternal cigarette smoking (OR: 2.20) were also associated with inadequate sleep and increased night waking, respectively.At age 2 y, higher consumption of soft drinks/snacks/fast foods is associated with shorter, more disrupted sleep. Conversely, higher vegetable consumption is associated with less disrupted sleep. Dietary modifications may improve toddlers' sleep.

ObjectivesTo investigate the perceptions and experiences of people with specific immune-mediated inflammatory diseases during the process of switching from Humira to biosimilar adalimumab.DesignCross-sectional survey.SettingAn anonymised, self-administered, web-based survey.ParticipantsThe participants were drawn from members and non-members of either the National Rheumatoid Arthritis Society, the National Axial Spondyloarthritis Society, Crohn’s and Colitis UK, or Psoriasis Association. Birdshot Uveitis Society and Olivia’s Vision also signposted to the survey links.ResultsA total of 899 people living with various immune mediated inflammatory diseases participated in this survey. Thirty-four per cent of respondents reported poor overall satisfaction with their biosimilar adalimumab after the switch, associated with complaints related to the switching process including lack of shared decision making, scarcity of information provided by or signposted to by the department instigating the switch as well as lack of training with the new injection device. Where training with the new device had been provided, there were significantly reduced reports of pain when injecting the new biosimilar (OR 0.20, 95% CI 0.07 to 0.55), side effects (OR 0.17, 95% CI 0.06 to 0.47) and difficulty in using the new injection device (OR 0.25, 95% CI 0.15 to 0.41). Self-reported side effects were reduced by (OR 0.13, 95% CI 0.05 to 0.38) when written information was provided by healthcare professionals and by (OR 0.15, 95% CI 0.05 to 0.42) with provision of verbal information. Difficulty in using the new injection device was also reduced by provision of satisfactory information such as written documents (OR 0.38, 95% CI 0.23 to 0.63) or by verbal communication with healthcare professionals (OR 0.45, 95% CI 0.27 to 0.73). Finally, provision of satisfactory written or verbal information was associated with a reduction in any negative perception regarding symptom control with the new biosimilar by (OR 0.05, 95% CI 0.004 to 0.57) and by (OR 0.15, 95% CI 0.03 to 0.84), respectively.ConclusionsPatient reported experiences of the process of switching from originator to biosimilar emphasise the importance of clear communication, training and information in order to optimise perception and maximise achievable outcomes with the new treatment.

Amid a global pandemic, unprecedented numbers of citizens relied on essential public employees as lifelines for their health, safety, and connectedness to the broader community. These public servants worked tirelessly through collective trauma to ensure their neighbors had what was needed to maintain some semblance of a routine in an otherwise unpredictable environment. This article uses narrative inquiry to examine the implications of the COVID-19 pandemic disruption on the public sector workplace, the quality of work life, and to investigate how employees coped during the crisis. Our research reports on interviews with 43 front-line and behind-the-scenes public employees who describe how they coped, maintained their public service motivation, and worked through increased demands for emotional labor in this new work-life environment. The findings suggest the need for human resources policies that allow for a flexible, reflective, holistic, and person-centered approach.