An investigation of factors affecting changes in health behaviours during the COVID-19 pandemic in a UK population-based cohort study.

OBJECTIVES: The COVID-19 pandemic has led to changes in behaviours, which may have different health effects in population subgroups. We investigated whether within-individual changes in health behaviours from before to during the pandemic differ by socio-economic deprivation, age or sex. STUDY DESIGN: Prospective cohort study. METHODS: Participants were recruited from the existing UK Fenland cohort study with measurements of health behaviours twice prepandemic (2005 to February 2020) and three times during the pandemic (July 2020 to April 2021). Health behaviours included daily servings of fruit and vegetables, units of alcohol consumed per week, smoking status, sleep duration and total and domain-specific physical activity energy expenditure. Sociodemographic information (English indices of multiple deprivation, education, occupation and ethnicity) and COVID-19 antibody status were also collected. Participants were grouped into three categories based on their English indices of multiple deprivation score: most, middle and least deprived. RESULTS: Participants were included if they had completed at least one measurement during the pandemic and one prepandemic (n = 3212). Fruit and vegetable consumption, total physical activity energy expenditure and smoking prevalence decreased during the pandemic compared with prepandemic, whereas average sleep duration increased and alcohol consumption did not change. Decreases in fruit and vegetable intake and physical activity energy expenditure were most pronounced in the most deprived group compared with the least deprived group and were greater in women than men. CONCLUSIONS: Socio-economic inequalities in health behaviours have worsened during the pandemic. As the country emerges from the COVID-19 pandemic, strategies to reduce health inequalities need to be put at the forefront of recovery plans.

Long-term in vitro maintenance of clonal abundance and leukaemia-initiating potential in acute lymphoblastic leukaemia.

Lack of suitable in vitro culture conditions for primary acute lymphoblastic leukaemia (ALL) cells severely impairs their experimental accessibility and the testing of new drugs on cell material reflecting clonal heterogeneity in patients. We show that Nestin-positive human mesenchymal stem cells (MSCs) support expansion of a range of biologically and clinically distinct patient-derived ALL samples. Adherent ALL cells showed an increased accumulation in the S phase of the cell cycle and diminished apoptosis when compared with cells in the suspension fraction. Moreover, surface expression of adhesion molecules CD34, CDH2 and CD10 increased several fold. Approximately 20% of the ALL cells were in G0 phase of the cell cycle, suggesting that MSCs may support quiescent ALL cells. Cellular barcoding demonstrated long-term preservation of clonal abundance. Expansion of ALL cells for >3 months compromised neither feeder dependence nor cancer initiating ability as judged by their engraftment potential in immunocompromised mice. Finally, we demonstrate the suitability of this co-culture approach for the investigation of drug combinations with luciferase-expressing primograft ALL cells. Taken together, we have developed a preclinical platform with patient-derived material that will facilitate the development of clinically effective combination therapies for ALL.

Beetroot supplementation lowers daily systolic blood pressure in older, overweight subjects.

Although inorganic nitrate and beetroot juice supplementation are associated with decreased systolic blood pressure (BP), these results have primarily been obtained from short-term trials that focused on healthy young adults. Therefore, we hypothesized that oral supplementation of beetroot juice concentrate would decrease systolic BP in overweight older participants but that the decline in BP would not be sustained after a 1-week interruption of the beetroot juice supplementation. For 3 weeks, 24 participants were randomized to either the beetroot juice concentrate or blackcurrant juice group, with a 1-week postsupplementation phase (week 4). Changes in systolic and diastolic BP were assessed during the supplementation and postsupplementation phases. Blood pressure was measured using 3 different methods: (1) resting clinic BP, (2) 24-hour ambulatory BP monitoring, and (3) home monitoring of daily resting BP. The first 2 methods were applied at baseline and after weeks 3 and 4. Daily measurements were conducted throughout the study, with 21 subjects completing the study (beetroot/blackcurrant = 10/11; male/female = 12/9; age = 62.0 ± 1.4 years; body mass index = 30.1 ± 1.2 kg/m(2)). After 3 weeks, beetroot juice supplementation was not associated with significant changes in resting clinic BP or 24-hour ABPM. Conversely, beetroot juice concentrate reduced daily systolic BP after 3 weeks (-7.3 ± 5.9 mm Hg, P = .02); however, the effect was not maintained after the interruption of the supplementation (week 4, 2.8 ± 6.1 mm Hg, P = .09). In overweight older subjects, beetroot juice concentrate supplementation was associated with beneficial effects on daily systolic BP, although the effects were not significant when measured by 24-hour ABPM or resting clinic BP.

Evaluation of waist-to-height ratio to predict 5 year cardiometabolic risk in sub-Saharan African adults.

BACKGROUND AND AIMS: Simple, low-cost central obesity measures may help identify individuals with increased cardiometabolic disease risk, although it is unclear which measures perform best in African adults. We aimed to: 1) cross-sectionally compare the accuracy of existing waist-to-height ratio (WHtR) and waist circumference (WC) thresholds to identify individuals with hypertension, pre-diabetes, or dyslipidaemia; 2) identify optimal WC and WHtR thresholds to detect CVD risk in this African population; and 3) assess which measure best predicts 5-year CVD risk. METHODS AND RESULTS: Black South Africans (577 men, 942 women, aged >30years) were recruited by random household selection from four North West Province communities. Demographic and anthropometric measures were taken. Recommended diagnostic thresholds (WC > 80 cm for women, >94 cm for men; WHtR > 0.5) were evaluated to predict blood pressure, fasting blood glucose, lipids, and glycated haemoglobin measured at baseline and 5 year follow up. Women were significantly more overweight than men at baseline (mean body mass index (BMI) women 27.3 ± 7.4 kg/m(2), men 20.9 ± 4.3 kg/m(2)); median WC women 81.9 cm (interquartile range 61-103), men 74.7 cm (63-87 cm), all P < 0.001). In women, both WC and WHtR significantly predicted all cardiometabolic risk factors after 5 years. In men, even after adjusting WC threshold based on ROC analysis, WHtR better predicted overall 5-year risk. Neither measure predicted hypertension in men. CONCLUSIONS: The WHtR threshold of >0.5 appears to be more consistently supported and may provide a better predictor of future cardiometabolic risk in sub-Saharan Africa.

Transmitochondrial embryonic stem cells containing pathogenic mtDNA mutations are compromised in neuronal differentiation.

OBJECTIVES: Defects of the mitochondrial genome (mtDNA) cause a series of rare, mainly neurological disorders. In addition, they have been implicated in more common forms of movement disorders, dementia and the ageing process. In order to try to model neuronal dysfunction associated with mitochondrial disease, we have attempted to establish a series of transmitochondrial mouse embryonic stem cells harbouring pathogenic mtDNA mutations. MATERIALS AND METHODS: Transmitochondrial embryonic stem cell cybrids were generated by fusion of cytoplasts carrying a variety of mtDNA mutations, into embryonic stem cells that had been pretreated with rhodamine 6G, to prevent transmission of endogenous mtDNA. Cybrids were differentiated into neurons and assessed for efficiency of differentiation and electrophysiological function. RESULTS: Neuronal differentiation could occur, as indicated by expression of neuronal markers. Differentiation was impaired in embryonic stem cells carrying mtDNA mutations that caused severe biochemical deficiency. Electrophysiological tests showed evidence of synaptic activity in differentiated neurons carrying non-pathogenic mtDNA mutations or in those that caused a mild defect of respiratory activity. Again, however, neurons carrying mtDNA mutations that resulted in severe biochemical deficiency had marked reduction in post-synaptic events. CONCLUSIONS: Differentiated neurons carrying severely pathogenic mtDNA defects can provide a useful model for understanding how such mutations can cause neuronal dysfunction.

Added sugars and micronutrient dilution.

There is increasing concern that high intakes of added sugars promote micronutrient dilution. However, the overall conclusion to emerge from the existing evidence base is that associations between reported intakes of added sugars and intakes of micronutrients are inconsistent and often non-linear, both across and within age groups, and between the genders. If a nutrient displacement effect does exist, a high consumption of added sugar does not necessarily compromise overall micronutrient intakes and similarly, consuming less added sugar is no guarantee that micronutrient intakes will be optimized. Clarification of this issue has been beset by methodological and conceptual difficulties. The observed associations between added sugars and micronutrient intake have been heavily contingent on both the definition of sugars chosen and the analytical approach used for adjusting for differences in reported energy intake. These issues have been further compounded by mis-reporting of food intake of unknown direction and magnitude and the cut-offs used to determine 'inadequate' micronutrient intakes which vary over time and between studies and countries. In the absence compelling evidence that micronutrient intakes are compromised by a high consumption of added sugars, it may now be appropriate to question the legitimacy of the nutrient dilution hypothesis as it is highly likely that it is oversimplifying more subtle and complex dietary issues. Recommendations for further research are made to help bring resolution to these issues.

Detection of genes with moderate effects on disease resistance using ovine mhc and resistance to nematodes as an example.

Detecting some of the genes that influence disease resistance would improve our understanding of the processes that cause disease and also simplify disease control. Genes within the major histocompatibility complex (mhc) are strong candidates for disease resistance and they have been intensely studied for the last 30 years. Recently, several groups working independently have reported the existence of alleles within the mhc that are associated with enhanced resistance to nematode infection. This article uses hindsight to describe some of the potential pitfalls that hinder the search for valid disease resistance genes. The search requires a good understanding of disease biology, molecular genetics, statistical genetics and especially, the design and analysis of experiments. The power to detect mhc effects is quite low and is quite sensitive to the frequency of the putative resistance alleles.

Childhood obesity prevention studies: lessons learned and to be learned.

OBJECTIVE: To provide an overview of methodological issues in the design, delivery and evaluation of childhood obesity prevention programmes. DESIGN: Review of existing literature. SETTING: International. RESULTS: Interventions have varied considerably with regard to their design, subject selection criteria, sample size, attrition rates, intervention components and duration of both the intervention and the follow-up phases. However, overall, there is only a limited body of consistent, high-quality evidence on which valid and generalisable conclusions can be drawn about best practices for the prevention of childhood obesity. CONCLUSIONS: Although the rationale for targeting children and adolescents through primary prevention is now compelling, effective obesity prevention remains elusive. There is increasing consensus that prevention of childhood obesity necessitates multifaceted health promotion interventions based on population health principles. By definition, such interventions should have a range of outcome indicators of effectiveness, generalisability and sustainability, not just the traditional ones focused on individual lifestyle behaviour change. Given the complexity and intricacy of population-based intervention programmes, multiple methods of data collection which combine both qualitative and quantitative approaches will need to be fully exploited in order to move towards evidence-based practice in the future.

Modeling channel properties in vestibular calyx terminals.

Two types of hair cell have been described in the vestibular end organs of amniotes, but the coding of sensory signals by different hair cell types is not well understood. Type I hair cells are contacted by cup-shaped afferent calyx terminals, whereas type II hair cells are contacted by bouton terminals. The whole cell patch-clamp technique has been used to record voltage-dependent ionic currents from calyx terminals. Type I hair cells along with their calyces were non-enzymatically dissociated from the semicircular canals and utricles of Mongolian gerbils. Voltage-dependent currents identified in whole cell voltage-clamp included transient inward sodium currents and outward potassium currents. Potassium currents were pharmacologically blocked by cesium in the patch electrode solution. The NEURON simulation environment was used to model the properties of the calyx terminal. A series of interconnected cylindrical compartments was designed to represent the inner and outer calyx membrane, the base of the calyx and a short axon segment. Kinetic parameters for the Na+ current were optimized with a genetic algorithm to match kinetic data from the whole cell recordings.

Secular trends in under-reporting in young people.

National survey data show that reported energy intake has decreased in recent decades despite a rise in the prevalence of obesity. This disparity may be due to a secular increase in under-reporting or a quantitatively greater decrease in energy expenditure. This study examines the extent of under-reporting of energy intake in the National Diet and Nutrition Survey (NDNS) in young people aged 4-18 years in 1997 using published equations to calculate estimated energy requirements. It explores secular changes by comparison with the Diets of British School Children (DBSC) survey in 10-11- and 14-15-year-olds in 1983. In the NDNS, under-reporting (estimated energy requirements--energy intake) represented 21 % of energy needs in girls and 20 % in boys. The magnitude of under-reporting increased significantly with age (P<0.001) and was higher in overweight than lean individuals over 7 years of age. To compare reported energy intake in DBSC and NDNS, the estimated physical activity level from dietary records (dPAL=reported energy intake/predicted BMR) was calculated. If there were no under-reporting, dPAL would represent the subject's true activity level. However, dPAL from the NDNS was significantly lower than that from the DBSC by 8 % and 9 % in boys and girls for those aged 10-11 years, and by 14 % and 11 % for 14-15-year-olds respectively, reaching physiologically implausible levels in the 14-15-year-old girls (dPAL=1.17). If activity levels have remained constant between the two surveys, under-reporting has increased by 8-14 %. The evidence supports a secular trend towards increased under-reporting between the two surveys, but the precise magnitude cannot be quantified in the absence of historical measures of energy expenditure.

Positive, site-specific associations between bone mineral status, fitness, and time spent at high-impact activities in 16- to 18-year-old boys.

The incidence of hip and forearm fracture in elderly men in the United Kingdom is a public health issue, but there is limited knowledge on lifestyle factors affecting male bone health. The aim of this cross-sectional study was to evaluate the relationships between whole body and regional bone mineral status and self-reported participation time in no-, low-, moderate-, and high-impact activities and fitness measurements in 16- to 18-year-old boys. One hundred twenty-eight boys underwent absorptiometry (DXA) measurements (Hologic QDR 1000W) of bone mineral content (BMC), bone area (BA), and bone mineral density (BMD) at the whole body, hip, spine, and forearm. They also completed the EPIC (European Prospective Investigation of Cancer) physical activity questionnaire, which allowed categorization of activities according to impact and aerobic intensity. Fitness and strength were assessed in each subject using estimated VO2 max, grip strength, and back strength. Significant positive relationships were found between BMC, BA, and BMD and the fitness and strength measurements and participation time in high-impact sports at most skeletal sites. The relationships were further examined after adjustment of BMC for height, weight, and bone area, thereby minimizing the influence of body and bone size on these relationships. VO2 max was a significant positive determinant of size-adjusted BMC at the whole body, the ultradistal and one-third radius, and all the hip sites, except the trochanter. Size-adjusted BMC at the forearm sites and trochanter was significantly positively associated with grip strength. Size-adjusted BMC at the whole body and all the hip sites was significantly positively associated with time spent at high-impact activities. Differences in size-adjusted BMC across thirds of time spent at high-impact activities were also examined. Boys in the highest third of high-impact activity had significantly greater size-adjusted whole body BMC and total hip BMC compared to subjects in the lowest third [+3.4 (1.2)% for whole body and +8.5 (2.2)% for hip, both P = 0.001]. Boys in the highest third of high-impact activity spent most activity time jogging, playing tennis, football and rugby, basketball, and exercising with weights. Back strength and lean mass were significantly greater in subjects in the highest third compared to those in the middle (P = 0.02) and lowest third (P = 0.03). No significant differences were found between subjects in each third of high-impact activity for potential confounders including TV viewing, calcium intake, body fat, and height. These findings indicate that participation of male adolescents in a range of high-impact activities for 1 h or more a day is associated with greater bone size and mineral content, especially at the hip.

Prevalence of obesity in Great Britain.

Since 1980 the prevalence of obesity in Great Britain in adults has almost trebled. Latest figures show that 23% of men and 25% of women were obese in 2002. In children, obesity prevalence is lower but the increase in the prevalence of overweight is similar to the rise in obesity in adults. Data from national surveys also show that there are marked differences in the prevalence of obesity that underpin health inequalities. Obesity is higher in low social classes, some ethnic minority groups particularly from South Asia and in Scotland and Wales relative to England.

Mechano-electrical transduction in the turtle utricle.

Two classes of mechano-sensory hair cell are present in the vestibular system of mammals, birds and reptiles. Type I hair cells are bottle-shaped and make synaptic contact with afferent calyx terminals. Type II hair cells are cylindrical and contact small bouton afferent terminals. Voltage-dependent basolateral currents have been found to differ between the two cell types and these properties are believed to contribute to the shaping of primary afferent responses. Type I hair cells have a low input resistance, which may be related to the low gain of calyx afferents. In the turtle utricle, type I vestibular hair cells are found only in a narrow band of the sensory epithelium called the striola, whereas type II hair cells are found in both striolar and extrastriolar regions. We have made whole cell patch clamp recordings from type I hair cells, type II hair cells and calyx fibers in order to better understand the processing of vestibular signals. Here we describe responses of hair cells to hair bundle displacement with a stiff glass probe. Mechano-electrical transduction (MET) currents were largest in type I hair cells, where the mean peak amplitude was approximately 500 pA. MET currents in all hair cells showed rapid and slow adaptation.

Association of the metabolic syndrome with both vigorous and moderate physical activity.

BACKGROUND: Cross-sectional relationships between moderate and vigorous physical activity and the metabolic syndrome (MS) were examined in the Whitehall II study of civil servants (age 45-68 years). We assessed cardiovascular fitness and body mass index (BMI) as possible mediators of the observed association. METHODS: Measures of 2-hour glucose, systolic blood pressure, fasting triglycerides, waist-hip ratio, and high density lipoprotein (HDL) cholesterol were obtained in 5153 white European participants. Participants in the most adverse sex-specific quintile for three or more of these risk factors were classified as having MS. Self-reported leisure-time physical activity was categorized into separate moderate and vigorous activity classes. BMI and resting heart rate (HR) were used to estimate body fatness and cardiovascular fitness respectively. RESULTS: The odds ratios (95% CI) for having the metabolic syndrome in the top categories of vigorous and moderate activity were 0.52 (95% CI: 0.40, 0.67) and 0.78 (95% CI: 0.63, 0.96) respectively, adjusted for age, sex, smoking, alcohol intake, socioeconomic status, and other activity. Adjustment for BMI and resting HR substantially attenuated both of the above associations. CONCLUSIONS: Moderate and vigorous physical leisure-time activity are each associated with reduced risk of being classified with MS independently of age, smoking, and high alcohol intake. Both vigorous and moderate activities may be beneficial to the MS cluster of risk factors among middle-aged populations. Reduced BMI and increased cardiovascular fitness may be important mediators of this association for both intensities of activity.

Nutritional management of rheumatoid arthritis: a review of the evidence.

Rheumatoid arthritis (RA) is a debilitating disease and is associated with increased risk of cardiovascular disease and osteoporosis. Poor nutrient status in RA patients has been reported and some drug therapies, such as nonsteroidal anti-inflammatory drugs (NSAIDs), prescribed to alleviate RA symptoms, may increase the requirement for some nutrients and reduce their absorption. This paper reviews the scientific evidence for the role of diet and nutrient supplementation in the management of RA, by alleviating symptoms, decreasing progression of the disease or by reducing the reliance on, or combating the side-effects of, NSAIDs. Supplementation with long-chain n-3 polyunsaturated fatty acids (PUFA) consistently demonstrates an improvement in symptoms and a reduction in NSAID usage. Evidence relating to other fatty acids, antioxidants, zinc, iron, folate, other B vitamins, calcium, vitamin D and fluoride are also considered. The present evidence suggests that RA patients should consume a balanced diet rich in long-chain n-3 PUFA and antioxidants. More randomized long-term studies are needed to provide evidence for the benefits of specific nutritional supplementation and to determine optimum intake, particularly for n-3 PUFA and antioxidants.

Return of potassium ion channels in regenerated hair cells: possible pathways and the role of intracellular calcium signaling.

Recent electrophysiological studies in pigeon have demonstrated that potassium channels are completely functional in regenerated type II hair cells at 21 days post-treatment (PT) with ototoxic doses of streptomycin. The currents return in the order they appear during development. The mixture of ionic currents in a regenerated type II hair cell in a particular region of the neuroepithelium is the same as in its ancestor in that region. The return of currents in regenerated type I hair cells is more complicated. The dominant conductance gKI is not present until after 70 days PT. Before 70 days, the ionic currents in type I hair cells resemble those of regenerated type II hair cells, suggesting that the ionic currents in type II hair cells might be precursors of the ionic currents in regenerated type I hair cells. New data show that at one year PT, the kinetics and drug sensitivity of the dominant K+ conductance in type I hair cells are identical to gKI. Supporting cells, believed to be the precursors of regenerated type II hair cells, have effectively no voltage-gated outward potassium channels, suggesting that regenerated type II hair cells must develop these channels de novo. The next step is to understand the mechanisms by which the potassium channel protein is synthesized, migrates through the cytosol, and is inserted into the plasmalemma of regenerating hair cells. These mechanisms are unknown. We propose that intracellular calcium is involved in this process, as well as in the differentiation, proliferation, and gene regulation of precursor cells fated to become hair cells.

Estimating energy expenditure by heart-rate monitoring without individual calibration.

UNLABELLED: Heart rate monitoring has been shown to be a valid method for measuring free-living energy expenditure at the group level, but its use in large-scale studies is limited by the need for an individual calibration of the relationship between heart rate and energy expenditure. PURPOSE: To determine whether energy expenditure can be estimated from heart rate monitoring without individual calibration in epidemiological studies. METHODS: Our previously validated heart rate monitoring method relies on measuring individual calibration parameters obtained from resting energy expenditure and the regression line between energy expenditure and heart rate during exercise. We developed prediction equations for these parameters using easily measured variables in a population-based study of 789 individuals. The predictive ability of these parameters was tested in a separate population-based sample (N = 97). RESULTS: Physical activity level (PAL = total energy expenditure/basal metabolic rate) using the four estimated parameters was correlated with PAL using the measured parameters (r = 0.82, P < 0.01). Comparison of measured and estimated PAL showed that 97.9% of the scores were placed in the same or adjacent quartile. CONCLUSION: A combination of simple measurements and heart rate monitoring produces estimates of energy expenditure that are highly correlated with those obtained using full individual calibration. This simplification of the heart rate monitoring method could extend its use in ranking individuals in epidemiological studies.

Effects of KCNQ channel blockers on K(+) currents in vestibular hair cells.

Linopirdine and XE991, selective blockers of K(+) channels belonging to the KCNQ family, were applied to hair cells isolated from gerbil vestibular system and to hair cells in slices of pigeon crista. In type II hair cells, both compounds inhibited a slowly activating, slowly inactivating component of the macroscopic current recruited at potentials above -60 mV. The dissociation constants for linopirdine and XE991 block were <5 microM. A similar component of the current was also blocked by 50 microM capsaicin in gerbil type II hair cells. All three drugs blocked a current component that showed steady-state inactivation and a biexponential inactivation with time constants of approximately 300 ms and 4 s. Linopirdine (10 microM) reduced inward currents through the low-voltage-activated K(+) current in type I hair cells, but concentrations up to 200 microM had little effect on steady-state outward K(+) current in these cells. These results suggest that KCNQ channels may be present in amniote vestibular hair cells.

Physical activity patterns in a nationally representative sample of adults in Ireland.

OBJECTIVE: To evaluate habitual levels of physical activity in a nationally representative sample of adults in Ireland. DESIGN: Cross-sectional survey using a self-administered questionnaire. Usual levels of work, recreational and household activities were evaluated in relation to anthropometric, demographic and socio-economic characteristics. The amount and intensity of all activities were quantified by assigning metabolic equivalents (METS) to each activity. SETTING: Republic of Ireland and Northern Ireland, 1997-1999. SUBJECTS: Random sample of 1379 adults aged 18-64 years. RESULTS: Men were approximately twice as active in work and recreational activity (139.7 +/- 83.9 METS) as women (68.5 +/- 49.8 METS; P<0.001) but women were three times more active in household tasks (65.9 +/- 58.7 METS vs. 22.6 +/- 24.6 METS; P<0.001). Overall levels of physical activity declined with increasing age, particularly leisure activity in men. In women the decline in work activity was offset by spending more time in household pursuits. Twenty-five per cent of the subjects were extremely overweight (body mass index (BMI>28 kg m(-2)) or obese (BMI >30 kg m (-2)). Fewer obese subjects reported higher levels of work and leisure activities. However, a higher percentage of obese women reported participation in the higher levels of household activities. Participation rates in recreational activities were low. Walking was the most important leisure activity of both men (41%) and women (60%). In terms of hours per week spent in vigorous physical activity, men were more active than women, professional and skilled non-manual women were more active than women in other social classes, and younger subjects (aged 18-35 years) were more active than older subjects. CONCLUSIONS: The holistic approach used in the assessment of physical activity in this study has revealed important and subtle differences in the activity patterns of men and women. Failure to fully characterise the respective activity patterns of men and women could lead to ill-informed public health policy aimed at promoting and sustaining lifetime habits of physical activity. The results suggest that simple population-focused programmes to promote physical activity are unlikely to offer the same chance of long-term success as more sensitive and individualised strategies.