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.

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.

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.

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.

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.

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.

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.

Quantifying the association between habitual energy expenditure and blood pressure.

BACKGROUND: Previous studies have demonstrated an association between physical inactivity and hypertension, but the methods used to assess activity have been subjective and imprecise. Recently methods have become available allowing measurement of energy expenditure in free-living populations. Our aim was to employ these methods to assess the independent association between energy expenditure, cardio-respiratory fitness and blood pressure. METHODS: In a cross-sectional study of 775 people (45-70 years) participating in a continuing population-based cohort study, energy expenditure was assessed by 4 days of heart rate monitoring with individual calibration of the relationship between heart rate and energy expenditure, a method validated against doubly-labelled water and whole body calorimetry. Cardio-respiratory fitness was assessed in a sub-maximal test. To adjust for measurement error in the assessment of usual energy expenditure and fitness, 190 subjects repeated both tests on three further occasions at 4-monthly intervals. RESULTS: A highly significant linear trend in blood pressure was found across quintiles of the physical activity level, the ratio of total energy expenditure to basal metabolic rate. The differences in the mean systolic/diastolic blood pressure between the top and bottom quintile was 6.3/4.4 mmHg in men and 10.7/5.9 mmHg in women. These effects were independent of obesity and cardio-respiratory fitness. Correction for measurement error suggests that the true underlying relationship between usual energy expenditure and blood pressure is stronger still. CONCLUSIONS: These findings are compatible with a strong association between usual energy expenditure and blood pressure and support public health strategies aimed at increasing overall energy expenditure.

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.

In vitro activity of dirithromycin, a new macrolide antibiotic, against Mycoplasma species.

Dirithromycin is a new macrolide antibiotic that achieves high tissue concentration. We compared its in vitro activity against Mycoplasma species with that of erythromycin and tetracycline. Clinical isolates of M. pneumoniae (40), M. hominis (40), and Ureaplasma urealyticum (40) were tested against serial dilutions of three antibiotics using a microtiter plate method. Minimum inhibitory concentrations (MIC) were read as the lowest concentration of antibiotic yielding no color change in the broth. Neither macrolide antibiotic exhibited antimicrobial activity against M. hominis; MIC50 and MIC90 for tetracycline were 0.6 and 32 micrograms/ml, respectively. MIC50 for U. urealyticum was 4.0 micrograms/ml for dirithromycin, 2.0 micrograms/ml for erythromycin, and 1.0 micrograms/ml for tetracycline. MIC90 for U. urealyticum was > 128 micrograms/ml for all three agents. Against M. pneumoniae dirithromycin exhibited MIC50 of 0.1 micrograms/ml and MIC90 of 0.1 micrograms/ml. Both values for erythromycin were 0.2 micrograms/ml; for tetracycline they were 0.1 and 1.0 micrograms/ml, respectively. These results demonstrate the high in vitro activity of dirithromycin against M. pneumoniae and suggest that this agent may have a role in the treatment of respiratory Mycoplasma infections.

Effects of extracellular ATP on hair cells isolated from the guinea-pig semicircular canals.

Externally applied ATP (100 microM) induced membrane currents in type I and type II vestibular hair cells enzymatically isolated from guinea-pig semicircular canals. In whole-cell voltage-clamp and with 140 mM K+ in the pipette solution, ATP evoked an inwardly directed current in 58% of the cells when held at potentials below -40 mV. In the remainder, external ATP produced an outward current. After block of the K currents, an inward current activated by ATP was revealed at -50 mV. Intracellular Ca2+ levels were monitored using the Ca2+ indicator Fura-2 and were found to rise in both hair cell types in response to ATP. These results strongly suggest that ATP directly controls the entry of Ca2+ into crista hair cells which can then further modulate K+ currents.

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.

A combined heart rate and movement sensor: proof of concept and preliminary testing study.

OBJECTIVE: Heart rate monitoring has previously been used as a technique for measuring energy expenditure (EE) in field studies. However, the combination of heart rate monitoring with movement sensoring could have theoretical advantages compared to either method used alone. Therefore, this study was undertaken to develop and validate a new combined heart rate monitor and movement sensor instrument (HR+M) for measuring EE. METHODS: The HR+M instrument is a single-piece instrument worn around the chest which records minute-by-minute heart rate and movement. Eight subjects underwent an individual calibration in which EE and heart rate were measured at rest and during a sub-maximal bicycle ergometer test. They then wore the HR+M for 24 hours in a whole-body calorimeter and underwent a standard protocol including periods of physical activity and inactivity. Minute-by-minute heart rate was converted to EE using individual calibration curves with the motion data discriminating between periods of inactivity and activity at low heart rate levels. EE was also calculated using the HRFlex method which relies on heart rate alone. Both estimates of EE were compared to EE measured in the whole-body calorimeter. RESULTS: The mean percentage error of the HR+M method calculating TEE compared with the gold standard of the calorimeter measurement was 0.00% (95% CI of the mean error -0.25, 1. 25). The HRFlex method using the heart rate information alone resulted in a mean percentage error of 16.5% (95% CI of the mean error -0.57, 1.76). CONCLUSIONS: This preliminary test of HR+M demonstrates its ability to estimate EE and the pattern of EE and activity throughout the day. Further validation studies in free-living individuals are necessary. SPONSORSHIP: NJW is an MRC Clinician Scientist Fellow. KLR holds an MRC PhD scholarship.

Ionic currents in isolated vestibular hair cells from the guinea-pig crista ampullaris.

Ionic currents have been recorded under whole cell patch clamp in cells isolated from the guinea-pig vestibular system. Type I and type II cells were separately identified. Type II cells were further classified as short (less than 15 microns in length) or tall (greater than 15 microns). Under whole cell voltage clamp, cells showed an outward current which activated at potentials above about -50 mV, and tail currents which reversed near the potassium equilibrium potential. The outward current was reduced in the presence of external 10 mM tetraethylammonium or cadmium ions and when calcium was removed from the external medium. A small cadmium-sensitive transient inward current, a putative calcium current, was observed in cells loaded with caesium from the patch pipette. In 27 out of 64 cells a component of the recorded outward current inactivated. Such current components were most common in tall type II cells. This inactivating component was blocked by 4-aminopyridine and removed by depolarizing prepulses consistent with it being an A-type potassium current. Type I cells, on the other hand, showed mainly a non-inactivating outward current which slowly relaxed on repolarization to resting potentials. When membrane potentials were measured under current clamp, injections of less than 100 pA produced a single, highly damped transient followed by a plateau in Type II cells. No such transient was present in Type I cells. There is thus little evidence for an electrical resonance in these cells.

Vestibular type I and type II hair cells. 1: Morphometric identification in the pigeon and gerbil.

Classically, type I and type II vestibular hair cells have been defined by their afferent innervation patterns. Little quantitative information exists on the intrinsic morphometric differences between hair cell types. Data presented here define a quantitative method for distinguishing hair cell types based on the morphometric properties of the hair cell's neck region. The method is based initially on fixed histological sections, where hair cell types were identified by innervation pattern, type I cells having an afferent calyx. Cells were viewed using light microscopy, images were digitized, and measurements were made of the cell body width, the cuticular plate width, and the neck width. A plot of the ratio of the neck width to cuticular plate width (NPR) versus the ratio of the neck width to the body width (NBR) established four quadrants based on the best separation of type I and type II hair cells. The combination of the two variables made the accuracy of predicting either type I or type II hair cells greater than 90%. Statistical cluster analysis confirmed the quadrant separation. Similar analysis was performed on dissociated hair cells from semicircular canal, utricle, and lagena, giving results statistically similar to those of the fixed tissue. Additional comparisons were made between fixed tissue and isolated hair cells as well as across species (pigeon and gerbil) and between end organs (semicircular canal, utricle, and lagena). In each case, the same morphometric boundaries could be used to establish four quadrants, where quadrant 1 was predominantly type I cells and quadrant 3 was almost exclusively type II hair cells. The quadrant separations were confirmed statistically by cluster analysis. These data demonstrate that there are intrinsic morphometric differences between type I and type II hair cells and that these differences can be maintained when the hair cells are dissociated from their respective epithelia.

Vestibular type I and type II hair cells. 2: Morphometric comparisons of dissociated pigeon hair cells.

Morphometric properties of solitary hair cells dissociated from the semicircular canals (SCC), utricles (UTR), and lagenas (LAG) of adult white king pigeons, Columbia livia, were compared. Measurements were made of the cell body, cuticular plate and hair bundle. Cells were divided into two groups: type 1 (group 1) was predominantly type I hair cells, and type 2 (group 3) was primarily type II hair cells. Comparisons are made initially between end organs for each group. A subpopulation of short otolith hair cells was identified. Quantitative comparisons between isolated type 1 and type 2 hair cells demonstrated that type 1 hair cells were more homogeneous both within and between vestibular end organs; while they had shorter, thinner neck regions, narrower apical surfaces, with longer and thinner bodies than did type 2 hair cells. Generally, for both type 1 and type 2 hair cells, two different hair bundle shapes were present, those (unimodal) with a single sharp taper from longest to shortest stereocilia, and those (bimodal) with an initial steep taper followed by a less steep taper. An additional subtype of type 1 hair cells with short hair bundles was identified. SCC hair cells have fewer hair bundles with bimodal tapers across all cell groups when compared to UTR or LAG. All cell subtypes identified for dissociated hair cells were corroborated using histologic sections.

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.

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.