Clinical and biomechanical factors associated with falls and rheumatoid arthritis: baseline cohort with longitudinal nested case-control study.

OBJECTIVE: To identify the clinical and biomechanical characteristics associated with falls in people with RA. METHODS: A total of 436 people ≥60 years of age with RA completed a 1 year prospective survey of falls in the UK. At baseline, questionnaires recorded data including personal and medical history, pain and fatigue scores, health-related quality of life (HRQoL), physical activity and medication history. The occurrence of falls wasmonitored prospectively over 12 months by monthly self-reporting. A nested sample of 30 fallers (defined as the report of one or more falls in 12 months) and 30 non-fallers was evaluated to assess joint range of motion (ROM), muscle strength and gait parameters. Multivariate regression analyses were undertaken to determine variables associated with falling. RESULTS: Compared with non-fallers (n = 236), fallers (n = 200) were older (P = 0.05), less likely to be married (P = 0.03), had higher pain scores (P < 0.01), experienced more frequent dizziness (P < 0.01), were frequently taking psychotropic medications (P = 0.02) and reported lower HRQoL (P = 0.02). Among those who underwent gait laboratory assessments, compared with non-fallers, fallers showed a greater anteroposterior (AP; P = 0.03) and medial-lateral (ML) sway range (P = 0.02) and reduced isokinetic peak torque and isometric strength at 60° knee flexion (P = 0.03). Fallers also showed shorter stride length (P = 0.04), shorter double support time (P = 0.04) and reduced percentage time in swing phase (P = 0.02) and in knee range of motion through the gait cycle (P < 0.01). CONCLUSION: People with RA have distinct clinical and biomechanical characteristics that place them at increased risk of falling. Assessment for these factors may be important to offer more targeted rehabilitation interventions.

Adolescent time use and mental health: a cross-sectional, compositional analysis in the Millennium Cohort Study.

OBJECTIVE: To examine the association of 24-hour time-use compositions with mental health in a large, geographically diverse sample of UK adolescents. DESIGN: Cross-sectional, secondary data analysis. SETTING: Millennium Cohort Study (sixth survey), a UK-based prospective birth cohort. PARTICIPANTS: Data were available from 4642 adolescents aged 14 years. Analytical samples for weekday and weekend analyses were n=3485 and n=3468, respectively (45% boys, 85% white ethnicity). PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures were the Strengths and Difficulties Questionnaire (SDQ, socioemotional behaviour), Mood and Feelings Questionnaire (MFQ, depressive symptoms) and Rosenberg Self-Esteem Scale (RSE, self-esteem). Behavioural exposure data were derived from 24-hour time-use diaries. RESULTS: On weekdays, participants spent approximately 54% of their time in sleep, 3% in physical activity, 9% in school-related activities, 6% in hobbies, 11% using electronic media and 16% in domestic activities. Predicted differences in SDQ, MFQ and RSE were statistically significant for all models (weekday and weekend) that simulated the addition or removal of 15 min physical activity, with an increase in activity being associated with improved mental health and vice versa. Predicted differences in RSE were also significant for simulated changes in electronic media use; an increase in electronic media use was associated with reduced self-esteem. CONCLUSION: Small but consistent associations were observed between physical activity, electronic media use and selected markers of mental health. Findings support the delivery of physical activity interventions to promote mental health during adolescence, without the need to specifically target or protect time spent in other activities.

Reduced cognitive ability in people with rheumatoid arthritis compared with age-matched healthy controls.

OBJECTIVE: The aim was to compare the cognitive ability of people with RA with healthy controls (HCs). METHODS: People with RA were recruited from the Norfolk Arthritis Register (NOAR), a population-based cohort study of people with inflammatory arthritis. Data on aged-matched HCs (people with no cognitive impairment) came from the comparison arm of The Dementia Research and Care Clinic Study (TRACC). People with RA and HCs performed a range of cognitive ability tasks to assess attention, memory, verbal fluency, language, visuospatial skills, emotional recognition, executive function and theory of mind. A score of <88 on the Addenbrooke's Cognitive Examination III was considered cognitive impairment. Scores were compared using linear regression adjusting for age, sex, smoking status, education, BMI, anxiety and depression. RESULTS: Thirty-eight people with RA [mean (S.D.) age: 69.1 (8.0) years; 25 (65.8%) women] were matched with 28 HCs [mean (S.D.) age: 68.2 (6.4) years; 15 (53.6%) women]. Twenty-three (60.5%) people with RA were considered to have mild cognitive impairment [mean (S.D.) Addenbrooke's Cognitive Examination III: RA = 85.2 (7.4), HC = 96.0 (2.5)]. People with RA had impairments in memory, verbal fluency, visuospatial functioning, executive function and emotional recognition in faces compared with HCs, after adjustment for confounders. CONCLUSION: People with RA had cognitive impairments in a range of domains. People with RA might benefit from cognitive impairment screening to allow for early administration of appropriate interventions.

Impact of COVID-19 pandemic social restriction measures on people with rheumatic and musculoskeletal diseases in the UK: a mixed-methods study.

OBJECTIVES: To determine the impact of COVID-19 pandemic social restriction measures on people with rheumatic and musculoskeletal diseases (RMDs) and to explore how people adapted to these measures over time. DESIGN: Mixed-methods investigation comprising a national online longitudinal survey and embedded qualitative study. SETTING: UK online survey and interviews with community-dwelling individuals in the East of England. PARTICIPANTS: People in the UK with RMDs were invited to participate in an online survey. A subsection of respondents were invited to participate in the embedded qualitative study. PRIMARY AND SECONDARY OUTCOME MEASURES: The online survey, completed fortnightly over 10 weeks from April 2020 to August 2020, investigated changes in symptoms, social isolation and loneliness, resilience and optimism. Qualitative interviews were undertaken assessing participant's perspectives on changes in symptoms, exercising, managing instrumental tasks such a shopping, medication and treatment regimens and how they experienced changes in their social networks. RESULTS: 703 people with RMDs completed the online survey. These people frequently reported a deterioration in symptoms as a result of COVID-19 pandemic social restrictions (52% reported increase vs 6% reported a decrease). This was significantly worse for those aged 18-60 years compared with older participants (p=0.017). The qualitative findings from 26 individuals with RMDs suggest that the greatest change in daily life was experienced by those in employment. Although some retired people reported reduced opportunity for exercise outside their homes, they did not face the many competing demands experienced by employed people and people with children at home. CONCLUSIONS: People with RMDs reported a deterioration in symptoms when COVID-19 pandemic social restriction measures were enforced. This was worse for working-aged people. Consideration of this at-risk group, specifically for the promotion of physical activity, changing home-working practices and awareness of healthcare provision is important, as social restrictions continue in the UK.

Trajectories of pain and function in the first five years after total hip and knee arthroplasty : an analysis of patient reported outcome data from the National Joint Registry.

AIMS: To determine the trajectories of patient reported pain and functional disability over five years following total hip arthroplasty (THA) or total knee arthroplasty (TKA). METHODS: A prospective, longitudinal cohort sub-study within the National Joint Registry (NJR) was undertaken. In all, 20,089 patients who underwent primary THA and 22,489 who underwent primary TKA between 2009 and 2010 were sent Oxford Hip Score (OHS) and Oxford Knee Score (OKS) questionnaires at six months, and one, three, and five years postoperatively. OHS and OKS were disaggregated into pain and function subscales. A k-means clustering procedure assigned each patient to a longitudinal trajectory group for pain and function. Ordinal regression was used to predict trajectory group membership using baseline OHS and OKS score, age, BMI, index of multiple deprivation, sex, ethnicity, geographical location, and American Society of Anesthesiologists grade. RESULTS: Data described two discrete trajectories for pain and function: 'level 1' responders (around 70% of cases) in whom a high level of improvement is sustained over five years, and 'level 2' responders who had sustained improvement, but at a lower level. Baseline patient variables were only weak predictors of pain trajectory and modest predictors of function trajectory. Those with worse baseline pain and function tended to show a greater likelihood of following a 'level 2' trajectory. Six-month patient-reported outcome measures data reliably predicted the class of five-year outcome trajectory for both pain and function. CONCLUSION: The available preoperative patient variables were not reliable predictors of postoperative pain and function after THA and TKA. Reviewing patient outcomes at six months postoperatively is a reliable indicator of outcome at five years. Cite this article: Bone Joint J 2021;103-B(6):1111-1118.

Cross-sectional associations between 24-hour activity behaviours and mental health indicators in children and adolescents: A compositional data analysis.

We examined associations between youth 24-hour activity behaviour compositions and mental health. Data were collected from 359 participants (aged 9-13 years). Activity behaviours (sleep, sedentary time (ST), light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA)) were assessed using wrist-worn accelerometers. Questionnaires and a computerized cognitive test battery assessed mental health outcomes. Linear mixed models examined associations between activity behaviour compositions and mental health. Post-hoc analyses modelled the influence of reallocating fixed durations of time between activity behaviours on mental health. ST was associated with worse internalizing problems (all participants; p< 0.05) and poorer prosocial behaviour (primary school participants only; p< 0.05), relative to the other activity behaviours. LPA was associated with worse cognitive test scores among primary school participants; p< 0.05). For all participants, reallocating time to ST from sleep and MVPA was associated with higher internalizing problems. Among primary school participants, reallocating time to ST from any other behaviour was associated with poorer prosocial behaviour, and reallocating time to LPA from any other behaviour was associated with lower executive function. Children's mental health may be promoted by schools integrating opportunities for MVPA throughout the day. Our results provide further evidence for the influence of daily activity behaviours on youth mental health.

Prescription of analgesia in emergency medicine (POEM) secondary analysis: an observational multicentre comparison of pain relief provided to adults and children with an isolated limb fracture and/or dislocation.

BACKGROUND: Acute pain is a common reason for emergency department (ED) attendance. Royal College of Emergency Medicine (RCEM) pain management audits have shown national variation and room for improvement. Previous evidence suggests that children receive less satisfactory pain management than adults. METHODS: Prescription of analgesia in emergency medicine is a cross-sectional observational study of consecutive patients presenting to 12 National Health Service EDs with an isolated long bone fracture and/or dislocation, and was carried out between 2015 and 2017. Using the recommendations in the RCEM Best Practice Guidelines, pain management in ED was assessed for differences of age (adults vs children) and hospital type (children's vs all patients). RESULTS: From the total 8346 patients, 38% were children (median age 8 years). There was better adherence to the RCEM guidance for children than adults (24% (766/3196) vs 11% (579/5123)) for the combined outcome of timely assessment, pain score and appropriate analgesia. In addition, children were significantly more likely than adults to receive analgesia appropriate to the pain score (of those with a recorded pain score 67% (1168/1744) vs 52% (1238/2361)). Children's hospitals performed much better across all reported outcomes compared with general hospitals. CONCLUSIONS: In contrast to previous studies, children with a limb fracture/dislocation are more likely than adults to have a pain score documented and to receive appropriate analgesia. Unexpectedly, children's EDs performed better than general EDs in relation to timely and appropriate analgesia but the reasons for this are not apparent from the present study.

Prescription Of analgesia in Emergency Medicine (POEM): a multicentre observational survey of pain relief in patients presenting with an isolated limb fracture and/or dislocation.

BACKGROUND: Acute pain is one of the most commonly cited reasons for attendance to the emergency department (ED), and the Royal College of Emergency Medicine (RCEM) Best Practice Guideline (2014) acknowledged that the current management of acute pain in UK EDs is inadequate and has a poor evidence base. METHODS: The Prescription Of analgesia in Emergency Medicine (POEM) survey is a cross-sectional observational survey of consecutive patients presenting to 12 National Health Service (NHS) EDs with limb fracture and/or dislocation in England and Scotland and was carried out between 2015 and 2017. The primary outcome was to assess the adequacy of pain management in the ED against the recommendations in the RCEM Best Practice Guidelines. RESULTS: In all, 8346 patients were identified as attending the ED with a limb fracture and/or dislocation but adherence to RCEM guidelines could only be evaluated for the 4160 (49.8%) patients with a recorded pain score. Of these, 2409/4160 (57.9%) patients received appropriate pain relief, but only 1347 patients were also assessed within 20 minutes of their arrival in the ED. Therefore, according to the RCEM guidelines, only 16.1% (1347/8346) of all patients were assessed and had satisfactory pain management in the ED. CONCLUSIONS: The POEM survey has identified that pain relief for patients with an isolated limb fracture remains inadequate when strictly compared to the RCEM Best Practice Guidelines. However, we have found that some patients receive analgesia despite having no pain score recorded, while other analgesic modalities are provided that are not currently encompassed by the Best Practice Guidelines. Future iterations of these guidelines may wish to encompass the breadth of available modalities of pain relief and the whole patient journey. In addition, more work is needed to improve timely and repeated assessment of pain and its recording, which has been better achieved in some EDs than others.

Demographic and geographical variability in physiotherapy provision following hip and knee replacement. An analysis from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.

BACKGROUND: Total hip (THR) and knee replacement (TKR) are two of the most common elective orthopaedic procedures worldwide. Physiotherapy is core to the recovery of people following joint replacement. However, there remains uncertainty as to physiotherapy provision at a national level. OBJECTIVES: To examine the relationship between patient impairment and geographical variation on the provision of physiotherapy among patients who undergo primary total hip or knee replacement (THR/TKR). DESIGN: Population-based observational cohort study. METHODS: Patients undergoing THR (n=17,338) or TKR (n=20,260) recorded in the National Joint Registry for England (NJR) between 2009 and 2010 and completed Patient Reported Outcome Measures (PROMs) questionnaires at Baseline and 12 months postoperatively. Data were analysed on the frequency of physiotherapy over the first postoperative year across England's Strategic Health Authorities (SHAs). Logistic regression analyses examined the relationship between a range of patient and geographical characteristics and physiotherapy provision. RESULTS: Following THR, patients were less likely to receive physiotherapy than following TKR patients ('some' treatment by a physiotherapist within 1st post operative year: 53% vs 79%). People with worse functional outcomes 12 months postoperatively, received more physiotherapy after THR and TKR. There was substantial variation in provision of physiotherapy according to age (younger people received more physiotherapy), gender (females received more physiotherapy) ethnicity (non-whites received more physiotherapy) and geographical location (40% of patients from South West received some physiotherapy compared to 40 73% in London after THR). CONCLUSIONS: There is substantial variation in the provision of physiotherapy nationally. This variation is not explained by differences in the patient's clinical presentation.

Dietary Iron Bioavailability: A Simple Model That Can Be Used to Derive Country-Specific Values for Adult Men and Women.

BACKGROUND: Reference intakes for iron are derived from physiological requirements, with an assumed value for dietary iron absorption. A new approach to estimate iron bioavailability, calculated from iron intake, status, and requirements was used to set European dietary reference values, but the values obtained cannot be used for low- and middle-income countries where diets are very different. OBJECTIVE: We aimed to test the feasibility of using the model developed from United Kingdom and Irish data to derive a value for dietary iron bioavailability in an African country, using data collected from women of child-bearing age in Benin. We also compared the effect of using estimates of iron losses made in the 1960s with more recent data for whole body iron losses. METHODS: Dietary iron intake and serum ferritin (SF), together with physiological requirements of iron, were entered into the predictive model to estimate percentage iron absorption from the diet at different levels of iron status. RESULTS: The results obtained from the 2 different methods for calculating physiological iron requirements were similar, except at low SF concentrations. At a SF value of 30 µg/L predicted iron absorption from the African maize-based diet was 6%, compared with 18% from a Western diet, and it remained low until the SF fell below 25 µg/L. CONCLUSIONS: We used the model to estimate percentage dietary iron absorption in 30 Beninese women. The predicted values agreed with results from earlier single meal isotope studies; therefore, we conclude that the model has potential for estimating dietary iron bioavailability in men and nonpregnant women consuming different diets in other countries.

Accumulation of Dietary S-Methyl Cysteine Sulfoxide in Human Prostate Tissue.

SCOPE: Observational studies have associated consumption of cruciferous vegetables with reduced risk of prostate cancer. This effect has been associated with the degradation products of glucosinolates-thioglycosides that accumulate within crucifers. The possible role of S-methyl cysteine sulfoxide, a metabolite that also accumulates in cruciferous vegetables, and its derivatives, in cancer prevention is relatively unexplored compared to glucosinolate derivatives. The hypothesis that consuming a broccoli soup results in the accumulation of sulfate (a SMCSO derivative) and other broccoli-derived metabolites in prostate tissue is tested. METHODS AND RESULTS: Eighteen men scheduled for transperineal prostate biopsy were recruited into a 4-week parallel single blinded diet supplementation study (NCT02821728). Nine men supplemented their diet with three 300 mL portions of a broccoli soup each week for four weeks prior to surgery. Analyses of prostate biopsy tissues reveal no detectable levels of glucosinolates and derivatives. In contrast, SMCSO is detected in prostate tissues of the participants, with significantly higher levels in tissue of men in the supplementation arm. SMCSO was also found in blood and urine samples from a previous intervention study with the identical broccoli soup. CONCLUSION: The consequences of SMCSO accumulation in prostate tissues and its potential role in prevention of prostate cancer remains to be investigated.

Association between musculoskeletal pain with social isolation and loneliness: analysis of the English Longitudinal Study of Ageing.

INTRODUCTION: Musculoskeletal pain is a prevalent health challenge for all age groups worldwide, but most notably in older adults. Social isolation is the consequence of a decrease in social network size with a reduction in the number of social contacts. Loneliness is the psychological embodiment of social isolation and represents an individual's perception of dissatisfaction in the quality or quantity of their social contacts. This study aims to determine whether a relationship exists between musculoskeletal pain and social isolation and loneliness. METHODS: A cross-sectional analysis of the English Longitudinal Study of Ageing (ELSA) cohort was undertaken. ELSA is a nationally representative sample of the non-institutionalised population of individuals aged 50 years and over based in England. Data were gathered on social isolation through the ELSA Social Isolation Index, loneliness through the University of California, Los Angeles (UCLA) Loneliness Scale and musculoskeletal pain. Data for covariates included physical activity, depression score, socioeconomic status, access to transport and demographic characteristics. Logistic regression analyses were undertaken to determine the relationship between social isolation and loneliness with pain and the additional covariates. RESULTS: A total of 9299 participants were included in the analysis. This included 4125 (44.4%) males, with a mean age of 65.8 years. There was a significant association where social isolation was lower for those in pain (odd ratio (OR): 0.87; 95% confidence intervals (CI): 0.75 to 0.99), whereas the converse occurred for loneliness where this was higher for those in pain (OR: 1.15; 95% CI: 1.01 to 1.31). Age, occupation, physical activity and depression were all associated with increased social isolation and loneliness. CONCLUSION: People who experience chronic musculoskeletal pain are at greater risk of being lonely, but at less risk of being socially isolated. Health professionals should consider the wider implications of musculoskeletal pain on individuals, to reduce the risk of negative health implications associated with loneliness from impacting on individual's health and well-being.

Transcriptional changes in prostate of men on active surveillance after a 12-mo glucoraphanin-rich broccoli intervention-results from the Effect of Sulforaphane on prostate CAncer PrEvention (ESCAPE) randomized controlled trial.

BACKGROUND: Epidemiological evidence suggests that consumption of cruciferous vegetables is associated with reduced risk of prostate cancer progression, largely attributed to the biological activity of glucosinolate degradation products, such as sulforaphane derived from glucoraphanin. Because there are few therapeutic interventions for men on active surveillance for prostate cancer to reduce the risk of cancer progression, dietary approaches are an appealing option for patients. OBJECTIVE: We evaluated whether consumption of a glucoraphanin-rich broccoli soup for 1 y leads to changes in gene expression in prostate tissue of men with localized prostate cancer. METHODS: Forty-nine men on active surveillance completed a 3-arm parallel randomized double-blinded intervention study for 12 mo and underwent transperineal template biopsy procedures and dietary assessment at the start and end of the study. Patients received a weekly 300 mL portion of soup made from a standard broccoli (control) or from 1 of 2 experimental broccoli genotypes with enhanced concentrations of glucoraphanin, delivering 3 and 7 times that of the control, respectively. Gene expression in tissues from each patient obtained before and after the dietary intervention was quantified by RNA sequencing followed by gene set enrichment analyses. RESULTS: In the control arm, there were several hundred changes in gene expression in nonneoplastic tissue during the 12 mo. These were associated with an increase in expression of potentially oncogenic pathways including inflammation processes and epithelial-mesenchymal transition. Changes in gene expression and associated oncogenic pathways were attenuated in men on the glucoraphanin-rich broccoli soup in a dose-dependent manner. Although the study was not powered to assess clinical progression, an inverse association between consumption of cruciferous vegetables and cancer progression was observed. CONCLUSION: Consuming glucoraphanin-rich broccoli soup affected gene expression in the prostate of men on active surveillance, consistent with a reduction in the risk of cancer progression. This trial was registered at clinicaltrials.gov as NCT01950143.

One-Year Consumption of a Mediterranean-Like Dietary Pattern With Vitamin D3 Supplements Induced Small Scale but Extensive Changes of Immune Cell Phenotype, Co-receptor Expression and Innate Immune Responses in Healthy Elderly Subjects: Results From the United Kingdom Arm of the NU-AGE Trial.

Amongst the major features of aging are chronic low grade inflammation and a decline in immune function. The Mediterranean diet (MedDiet) is considered to be a valuable tool to improve health status, and although beneficial effects have been reported, to date, immunological outcomes have not been extensively studied. We aimed to test the hypothesis that 1 year of a tailored intervention based on the MedDiet with vitamin D (10 µg/day) would improve innate immune responses in healthy elderly subjects (65-79 years) from the English cohort (272 subjects recruited) of the NU-AGE randomized, controlled study (clinicaltrials.gov, NCT01754012). Of the 272 subjects forming the United Kingdom cohort a subgroup of 122 subjects (61 in the intervention group and 61 in the control group) was used to evaluate ex vivo innate immune response, phenotype of circulating immune cells, and levels of pro- and anti-inflammatory markers. Odds Ratio (OR) was calculated for all the parameters analyzed. After adjustment by gender, MedDiet-females with a BMI < 31 kg/m2 had a significant upregulation of circulating CD40+CD86+ cells (OR 3.44, 95% CI 1.01-11.75, P = 0.0437). Furthermore, in all MedDiet subjects, regardless of gender, we observed a MedDiet-dependent changes, although not statistically significant of immune-critical parameters including T cell degranulation, cytokine production and co-receptor expression. Overall, our study showed that adherence to an individually tailored Mediterranean-like dietary pattern with a daily low dose of vitamin D3 supplements for 1 year modified a large variety of parameters of immune function in healthy, elderly subjects. We interpreted these data as showing that the MedDiet in later life could improve aspects of innate immunity and thus it could aid the design of strategies to counteract age-associated disturbances. Clinical Trial Registration: clinicaltrials.gov, NCT01754012.

Trajectory of physical activity after hip fracture: An analysis of community-dwelling individuals from the English Longitudinal Study of Ageing.

INTRODUCTION: To analyse physical activity participation in a community-dwelling people in England with hip fracture the interval prior to fracture, in the fracture recovery period, and a minimum of two years post-fracture. MATERIALS AND METHODS: 215 individuals were identified from the English Longitudinal Study of Ageing cohort (2002-2014) who sustained a hip fracture following a fall and for whom data were available on physical activity participation relating to the period pre-fracture, within-fracture recovery phase and post-fracture (minimum of two years). Physical activity was assessed using the validated ELSA physical activity questionnaire. Prevalence of 'low' physical activity participation was calculated and multi-level modelling analyses were performed to explore physical activity trajectories over the follow-up phase, and whether age, depression, gender and frailty were associated with physical activity participation. RESULTS: Prevalence of low physical activity participation within two years prior to hip fracture was 16.7% (95% Confidence Intervals (CI): 11.6% to 21.8%). This increased at the final follow-up phase to 21.3% (95% CI: 15.1% to 27.6%). This was not a statistically significant change (P = 0.100). Age (P = 0.005) and frailty (P < 0.001) were statistically significant explanatory variables (P = 0.005) where older age and greater frailty equated to lower physical activity participation. Neither gender (P = 0.288) nor depression (P = 0.121) were significant explanatory variables. CONCLUSION: Physical activity levels do not significantly change between pre-fracture to a minimum of two years post-hip fracture for community-dwelling individuals. This contrasts with previous reports of reduced mobility post-hip fracture, suggesting that 'physical activity' and 'mobility' should be considered as separate outcomes in this population.

Bioavailability of Glucoraphanin and Sulforaphane from High-Glucoraphanin Broccoli.

SCOPE: Broccoli accumulates 4-methylsulphinylbutyl glucosinolate (glucoraphanin) which is hydrolyzed to the isothiocyanate sulforaphane. Through the introgression of novel alleles of the Myb28 transcription factor from Brassica villosa, broccoli genotypes have been developed that have enhanced levels of glucoraphanin. This study seeks to quantify the exposure of human tissues to glucoraphanin and sulforaphane following consumption of broccoli with contrasting Myb28 genotypes. METHODS AND RESULTS: Ten participants are recruited into a three-phase, double-blinded, randomized crossover trial (NCT02300324), with each phase comprising consumption of 300 g of a soup made from broccoli of one of three Myb28 genotypes (Myb28B/B , Myb28B/V , Myb28V/V ). Plant myrosinases are intentionally denatured during soup manufacture. Threefold and fivefold higher levels of sulforaphane occur in the circulation following consumption of Myb28V/B and Myb28V/V broccoli soups, respectively. The percentage of sulforaphane excreted in 24 h relative to the amount of glucoraphanin consumed varies among volunteers from 2 to 15%, but does not depend on the broccoli genotype. CONCLUSION: This is the first study to report the bioavailability of glucoraphanin and sulforaphane from soups made with novel broccoli varieties. The presence of one or two Myb28V alleles results in enhanced delivery of sulforaphane to the systemic circulation.

Trajectory of social isolation following hip fracture: an analysis of the English Longitudinal Study of Ageing (ELSA) cohort.

Background: social isolation is defined as a lack of meaningful and sustained communication or interactions with social networks. There is limited understanding on the prevalence of social isolation and loneliness in people following hip fracture and no previous understanding of how this changes over time. Objective: to determine the prevalence and trajectory of social isolation and loneliness before a hip fracture, during the recovery phase and a minimum of 2 years post-hip fracture in an English population. Methods: data were from the English Longitudinal Study of Ageing (ELSA) cohort (2004/5-2014/15). The sample comprised of 215 participants who had sustained a hip fracture. Measures of social isolation and loneliness were analysed through multilevel modelling to determine their trajectories during three-time intervals (pre-fracture; interval at hip fracture and recovery; minimum 2 years post-fracture). The prevalence of social isolation and loneliness were determined pre- and post-fracture. Results: prevalence of social isolation was 19% post-hip fracture and loneliness 13% post-hip fracture. There was no statistically significant change in social isolation pre-fracture compared to a minimum of 2 years post-fracture (P = 0.78). Similarly, there was no statistically significant change in loneliness pre-fracture compared to a minimum of 2 years post-fracture (P = 0.12). Conclusion: this analysis has determined that whilst social isolation and loneliness do not change over time following hip fracture, these remain a significant problem for this population. Interventions are required to address these physical and psychological health needs. This is important as they may have short and longer term health benefits for people post-hip fracture.

A 1-h time interval between a meal containing iron and consumption of tea attenuates the inhibitory effects on iron absorption: a controlled trial in a cohort of healthy UK women using a stable iron isotope.

Background: Tea has been shown to be a potent inhibitor of nonheme iron absorption, but it remains unclear whether the timing of tea consumption relative to a meal influences iron bioavailability.Objective: The aim of the study was to investigate the effect of a 1-h time interval of tea consumption on nonheme iron absorption in an iron-containing meal in a cohort of iron-replete, nonanemic female subjects with the use of a stable isotope (57Fe).Design: Twelve women (mean ± SD age: 24.8 ± 6.9 y) were administered a standardized porridge meal extrinsically labeled with 4 mg 57Fe as FeSO4 on 3 separate occasions, with a 14-d time interval between each test meal (TM). The TM was administered with water (TM-1), with tea administered simultaneously (TM-2), and with tea administered 1 h postmeal (TM-3). Fasted venous blood samples were collected for iron isotopic analysis and measurement of iron status biomarkers. Fractional iron absorption was estimated by the erythrocyte iron incorporation method.Results: Iron absorption was 5.7% ± 8.5% (TM-1), 3.6% ± 4.2% (TM-2), and 5.7% ± 5.4% (TM-3). Mean fractional iron absorption was found to be significantly higher (2.2%) when tea was administered 1 h postmeal (TM-3) than when tea was administered simultaneously with the meal (TM-2) (P = 0.046). An ∼50% reduction in the inhibitory effect of tea (relative to water) was observed, from 37.2% (TM-2) to 18.1% (TM-3).Conclusions: This study shows that tea consumed simultaneously with an iron-containing porridge meal leads to decreased nonheme iron absorption and that a 1-h time interval between a meal and tea consumption attenuates the inhibitory effect, resulting in increased nonheme iron absorption. These findings are not only important in relation to the management of iron deficiency but should also inform dietary advice, especially that given to those at risk of deficiency. This trial was registered at clinicaltrials.gov as NCT02365103.

IL-6 Signaling Regulates Small Intestinal Crypt Homeostasis.

Gut homeostasis is a tightly regulated process requiring finely tuned complex interactions between different cell types, growth factors, or cytokines and their receptors. Previous work has implicated a role for IL-6 and mucosal immune cells in intestinal regeneration following injury and in promoting inflammation and cancer. We hypothesized that IL-6 signaling could also modulate crypt homeostasis. Using mouse in vitro crypt organoid and in vivo models, this study first demonstrated that exogenous IL-6 promoted crypt organoid proliferation and increased stem cell numbers through pSTAT3 activation in Paneth cells. Immunolabeling studies showed that the IL-6 receptor was restricted to the basal membrane of Paneth cells both in vitro and in vivo and that the crypt epithelium also expressed IL-6. Either a blocking Ab to the IL-6 receptor or a neutralizing Ab to IL-6 significantly reduced in vitro basal crypt organoid proliferation and budding, and in vivo significantly reduced the number of nuclei and the number of Lgr5EGFP-positive stem cells per crypt compared with IgG-treated mice, with the number of Paneth cells per crypt also significantly reduced. Functional studies demonstrated that IL-6-induced in vitro crypt organoid proliferation and crypt budding was abrogated by the Wnt inhibitor IWP2. This work demonstrates that autocrine IL-6 signaling in the gut epithelium regulates crypt homeostasis through the Paneth cells and the Wnt signaling pathway.

Modeling tool for calculating dietary iron bioavailability in iron-sufficient adults.

Background: Values for dietary iron bioavailability are required for setting dietary reference values. These are estimated from predictive algorithms, nonheme iron absorption from meals, and models of iron intake, serum ferritin concentration, and iron requirements.Objective: We developed a new interactive tool to predict dietary iron bioavailability.Design: Iron intake and serum ferritin, a quantitative marker of body iron stores, from 2 nationally representative studies of adults in the United Kingdom and Ireland and a trial in elderly people in Norfolk, United Kingdom, were used to develop a model to predict dietary iron absorption at different serum ferritin concentrations. Individuals who had raised inflammatory markers or were taking iron-containing supplements were excluded.Results: Mean iron intakes were 13.6, 10.3, and 10.9 mg/d and mean serum ferritin concentrations were 140.7, 49.4, and 96.7 mg/L in men, premenopausal women, and postmenopausal women, respectively. The model predicted that at serum ferritin concentrations of 15, 30, and 60 mg/L, mean dietary iron absorption would be 22.3%, 16.3%, and 11.6%, respectively, in men; 27.2%, 17.2%, and 10.6%, respectively, in premenopausal women; and 18.4%, 12.7%, and 10.5%, respectively, in postmenopausal women.Conclusions: An interactive program for calculating dietary iron absorption at any concentration of serum ferritin is presented. Differences in iron status are partly explained by age but also by diet, with meat being a key determinant. The effect of the diet is more marked at lower serum ferritin concentrations. The model can be applied to any adult population in whom representative, good-quality data on iron intake and iron status have been collected. Values for dietary iron bioavailability can be derived for any target concentration of serum ferritin, thereby giving risk managers and public health professionals a flexible and transparent basis on which to base their dietary recommendations. This trial was registered at clinicaltrials.gov as NCT01754012.