Randomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget's disease of bone.

INTRODUCTION: Paget's disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment. METHODS: We randomised 222 individuals at increased risk of PDB because of pathogenic SQSTM1 variants to receive 5 mg zoledronic acid (ZA) or placebo. The primary outcome was new bone lesions assessed by radionuclide bone scan. Secondary outcomes included change in existing lesions, biochemical markers of bone turnover and skeletal events related to PDB. RESULTS: The median duration of follow-up was 84 months (range 0-127) and 180 participants (81%) completed the study. At baseline, 9 (8.1%) of the ZA group had PDB lesions vs 12 (10.8%) of the placebo group. Two of the placebo group developed new lesions versus none in the ZA group (OR 0.41, 95% CI 0.00 to 3.43, p=0.25). Eight of the placebo group had a poor outcome (lesions which were new, unchanged or progressing) compared with none of the ZA group (OR 0.08, 95% CI 0.00 to 0.42, p=0.003). At the study end, 1 participant in the ZA group had lesions compared with 11 in the placebo group. Biochemical markers of bone turnover were significantly reduced in the ZA group. One participant allocated to placebo required rescue therapy with ZA because of symptomatic disease. The number and severity of adverse events did not differ between groups. CONCLUSIONS: Genetic testing for pathogenic SQSTM1 variants coupled with intervention with ZA is well tolerated and has favourable effects on the progression of early PDB. TRIAL REGISTRATION NUMBER: ISRCTN11616770.

Modification and simplification of Rongey's method for measurement of meat batter stability.

The method of Rongey for assessment and quantification of meat batter/emulsion stability has over the years proven useful to many research and industrial laboratories around the world. Unfortunately, its requirement for specialized glassware and a very large centrifugation unit makes the method inaccessible to many modern laboratories. We have, therefore, modified Rongey's original method by adapting it to present-day commercially-available glassware and centrifugation equipment. This modified method was validated by comparing it to Rongey's method on both high-fat (27%) and low-fat (10%) finely comminuted pork batters, each with and without the addition of salt (1.8%) and sodium phosphates (0.5%). This design provided us with batters ranging in stability from very low to very high, thus allowing us to compare the methods across analytical extremes. This modified method:•Utilizes glassware and centrifugation equipment that are commercially-available today.•Maintains the simplicity and speed of the original method of Rongey.•Yields results that are comparable to those of Rongey's traditional method.

Breastfeeding duration is associated with favorable body composition and lower glycoprotein acetyls in later life.

OBJECTIVE: The aim of the present study was to investigate associations between lifetime breastfeeding behaviors and cardiovascular risk in later reproductive years. METHOD: This was a prospective 10-year longitudinal cohort study of 168 parous women. Health, lifestyle and infant feeding questionnaires, blood samples, anthropometry and body composition were collected. Cardiovascular risk was estimated using QRISK®3 and hierarchical multiple linear regression analysis performed. RESULTS: Mean age was 42.4 years (SD 3.8; range 31-50) and 98.7% (n = 156/158) were premenopausal. Ever breastfeeding rates were 72.6% (n = 122/168) and 37.5% (n = 63/168) lifetime ≥12 months breastfeeding duration. Median durations were 5.5 weeks for exclusive breastfeeding (IQR 35.8; range 0-190) and 30.5 weeks for any breastfeeding (IQR 84.0; range 0-488). Breastfeeding duration was not associated with QRISK®3 scores in adjusted models. Lower glycoprotein acetyls were associated with ever breastfeeding (P = 0.03), and lifetime breastfeeding ≥12 months (P = 0.001). Lifetime breastfeeding ≥12 months and longer exclusive breastfeeding were associated with lower fat mass index (P = 0.03, P = 0.01), tissue percentage fat (P = 0.02, P = 0.009) and visceral adipose tissue volume (P = 0.04, P = 0.025) after correcting for confounders including body mass index. CONCLUSION: Longer breastfeeding is associated with favorable body composition and lower glycoprotein acetyls, a novel inflammatory biomarker associated with cardiometabolic risk. Breastfeeding is a low-cost, health promoting behavior for women and infants. Pregnant women, especially those at higher risk of cardiovascular disease, should be counseled about the potential benefits of exclusive and longer breastfeeding duration.

Childhood Nutritional Factors and Cardiometabolic Outcomes at 9-11 y of Age: Findings from the ROLO Longitudinal Birth Cohort Study.

BACKGROUND: Childhood represents a critical period of nutritional risk in the programming of later chronic disease. Few longitudinal studies have explored repeated measures of nutrition throughout the first decade of life in relation to preteen cardiometabolic outcomes. OBJECTIVES: This research aimed to explore associations of early feeding practices (human milk exposure and duration and timing of introduction to solids) and childhood dietary quality and inflammatory scores (at 5 and 9-11 y and change during childhood) on preteen cardiometabolic outcomes. METHODS: This is an analysis of children from the ROLO longitudinal birth cohort study (n = 399). Information on early feeding practices were obtained at postnatal study visits. Food frequency questionnaires collected maternal-reported dietary intakes for each child at 5 and 9-11 y of age. Healthy Eating Index (HEI)-2015 and the Children's Dietary Inflammatory Index (C-DII) scores were calculated. Anthropometry, body composition, blood pressure, heart rate, cardiorespiratory endurance, and blood biomarkers were obtained at 9-11 y. Crude and adjusted linear regression models examined nutritional exposure associations with preteen cardiometabolic outcomes. RESULTS: In the adjusted model, any human milk exposure was associated with lower body fat (%) at 9-11 y (ß: -2.86; 95% confidence interval [CI]: -5.46, -0.27; P = 0.03), than never receiving human milk. At 5 y, diet scores were favorably associated with lean mass at 9-11 y (P < 0.05 for both). Higher preteen HEI-2015 scores were associated with lower preteen leptin levels (tertile 3 compared with tertile 1-ß: -2.92; 95% CI: -5.64, -0.21; P = 0.03). Diet quality significantly deteriorated (HEI-2015 score decreased) and became more proinflammatory (C-DII score increased) from 5 to 9-11 y of age. Diet quality/inflammation deterioration (compared with improvement) or overall change in dietary scores were not related to preteen cardiometabolic outcomes. CONCLUSIONS: Exposure to human milk in early life was associated with lower preteen adiposity, irrespective of duration. Diet quality/inflammatory potential deteriorated between early childhood and the preteen years, highlighting a potential period for intervention.