Diabetic Retinopathy in Newly Diagnosed Subjects With Type 2 Diabetes Mellitus: Contribution of β-Cell Function

Purpose: The association of hyperglycemia and diabetic retinopathy (DR) in established type 2 diabetes mellitus (T2DM) subjects is well accepted. However, the association between β-cell responsiveness and insulin sensitivity leading to fasting and postprandial hyperglycemia with DR in newly diagnosed treatment-naïve T2DM subjects remain unreported. Methods: A total of 544 newly diagnosed treatment-naïve T2DM subjects were screened for DR (digital photography) and underwent a standardized meal tolerance test. Serial plasma glucose and insulin levels were measured, and fasting (M0) and postprandial β-cell responsiveness calculated Calculating Pancreatic Response Program along with homeostasis model assessment-β cell function (HOMA-B) and HOMA-Insulin Sensitivity. A subgroup of 201 subjects also underwent a frequently sampled IV glucose tolerance test and the acute insulin response to glucose, insulin sensitivity, and glucose effectiveness (SG) estimated (MINMOD model). Results: A total of 16.5% (90) subjects had DR at diagnosis. Subjects with DR had significantly reduced M0, HOMA-B and SG leading to higher fasting and postprandial (2 hour) glucose and significantly lower fasting and postprandial (2 hour) insulin. Factors independently associated with DR in multivariate logistic regression analysis were M0, HOMA-B, and SG with fasting and postprandial (2 hour) glucose and insulin. There was no statistical difference in glycated hemoglobin, systolic blood pressure, acute insulin response to glucose, and insulin sensitivity between those with or without DR. Principal Conclusions: In this cohort of newly diagnosed T2DM subjects, DR is associated with reduced β-cell responsiveness, resulting from β-cell failure rather than insulin resistance, leading to fasting and postprandial hyperglycemia and hypoinsulinemi

Chronic Urinary Infection in Overactive Bladder Syndrome: A Prospective, Blinded Case Control Study

Objectives: To investigate whether women with overactive bladder (OAB) symptoms and no evidence of clinical infection by conventional clean-catch midstream urine cultures have alternative indicators of sub-clinical infection.Patients/Subjects, Materials & Methods: The study was a prospective, blinded case-control study with 147 participants recruited, including 73 OAB patients and 74 controls. The OAB group comprised female patients of at least 18 years of age who presented with OAB symptoms for more than 3 months. Clean-catch midstream urine samples were examined for pyuria by microscopy; subjected to routine and enhanced microbiological cultures and examined for the presence of 10 different cytokines, chemokines, and prostaglandins by ELISA.Results: The mean age and BMI of participants in both groups were similar. No significant difference in the number of women with pyuria was observed between OAB and control groups (p = 0.651). Routine laboratory cultures were positive in three (4%) of women in the OAB group, whereas the enhanced cultures isolated bacteria in 17 (23.2%) of the OAB patients. In the control group, no positive cultures were observed using routine laboratory cultures, whereas enhanced culture isolated bacteria in 8 (10.8%) patients. No significant differences were observed in the concentrations of PGE2, PGF2α, MCP-1, sCD40L, MIP-1β, IL12p70/p40, IL12/IL-23p40, IL-5, EGF and GRO-α between the OAB and control groups.Conclusions: Patients with OAB symptoms have significant bacterial growth on enhanced culture of the urine, which is often not detectable through routine culture, suggesting a subclinical infection. Enhanced culture techniques should therefore be used routinely for the effective diagnosis and management of OAB

Objective profiling of varied human motion based on normative assessment of magnetometer time series data

Objective: To quantify varied human motion and obtain an objective assessment of relative performance across a cohort. Approach: A wrist-worn magnetometer was used to record and quantify the complex motion patterns of 55 children aged 10-12 years old, generated during a fundamental movement skills programme. Sensor-based quantification of the physical activity used dynamic time warping of the magnetometer time series data for pairs of children. Pairwise comparison across the whole cohort produced a similarity matrix of all child to child correlations. Normative assessment scores were based on the Euclidean distance between n participants within an n-1 multi-variate space, created from multi-dimensional scaling of the similarity matrix. The sensor-based scores were compared to the current standardised assessment which involves binary scoring of technique, outcome and time components by trained assessors. Main Results: Visualisation of the relative performance using the first three axes of the multi-dimensional matrix, shows a 'performance sphere' in which children sit on concentric shells of increasing radius as performance deteriorates. Good agreement between standard and sensor scores is found, with Spearman rank correlation coefficients of the overall activity score in the range of 0.62-0.71 for different cohorts and a kappa statistic of 0.34 for categorisation of all 55 children into lower, middle, upper tertile and top 5% bands. Significance: By using multi-dimensional analysis of similarity measures between participants rather than direct parameterisation of the physiological data, complex and varied patterns of physical motion can be quantified, allowing objective and robust profiling of relative function across participant groups

Poly(alkyl methacrylate) tooth coatings for dental care: evaluation of the demineralisation-protection benefit using a time-resolved in vitro method

An in vitro method for the time-resolved quantification of acid-mediated tooth demineralisation has been developed and evaluated against putative non-permanent protective formulations based on a series of poly(alkyl methacrylate)s. Using a thermostatted carousel, dentally relevant substrates consisting of hydroxyapatite discs or sections of bovine teeth have been exposed to aqueous citric acid under controlled conditions, before and after being treated with the polymeric coatings. The dissolution of phosphate was monitored by the determination of 31P by Inductively Coupled Plasma—Mass Spectrometry and by the spectrophotometric phosphovanadomolybdate method. Dose-response plots constructed for both groups of treated substrates have revealed that the coatings significantly reduce erosion rates but are less effective at inhibiting tooth demineralisation than the standard fluoride treatment. The approach has enabled an evaluation of the erosion-protection efficiency of each coating

Effectiveness and Safety of Adalimumab Biosimilar SB5 in IBD:Outcomes in Originator to SB5 Switch, Double Biosimilar Switch and Bio-Naieve SB5 Observational Cohorts

BACKGROUND AND AIMS: Multiple adalimumab [ADA] biosimilars are now approved for use in inflammatory bowel disease [IBD]; however, effectiveness and safety data remain scarce. We aimed to investigate long-term outcomes of the ADA biosimilar SB5 in IBD patients following a switch from the ADA originator [SB5-switch cohort] or after start of SB5 [SB5-start cohort]. METHODS: We performed an observational cohort study in a tertiary IBD referral centre. All IBD patients treated with Humira underwent an elective switch to SB5. We identified all these patients in a biological prescription database that prospectively registered all ADA start and stop dates including brand names. Data on IBD phenotype, C-reactive protein [CRP], drug persistence, ADA drug and antibody levels, and faecal calprotectin were collected. RESULTS: In total, 481 patients were treated with SB5, 256 in the SB5-switch cohort (median follow-up: 13.7 months [IQR 8.6–15.2]) and 225 in the SB5-start cohort [median follow-up: 8.3 months [4.2–12.8]). Of the SB5-switch cohort, 70.8% remained on SB5 beyond 1 year; 90/256 discontinued SB5, mainly due to adverse events [46/90] or secondary loss of response [37/90]. In the SB5-start cohort, 81/225 discontinued SB5, resulting in SB5-drug persistence of 60.3% beyond 1 year. No differences in clinical remission [p = 0.53], CRP [p = 0.80], faecal calprotectin [p = 0.40] and ADA trough levels [p = 0.55] were found between baseline, week 26 and week 52 following switch. Injection site pain was the most frequently reported adverse event. CONCLUSION: Switching from ADA originator to SB5 appeared effective and safe in this study with over 12 months of follow-up

High-quality de novo assembly of the apple genome and methylome dynamics of early fruit development

Using the latest sequencing and optical mapping technologies, we have produced a high-quality de novo assembly of the apple (Malus domestica Borkh.) genome. Repeat sequences, which represented over half of the assembly, provided an unprecedented opportunity to investigate the uncharacterized regions of a tree genome; we identified a new hyper-repetitive retrotransposon sequence that was over-represented in heterochromatic regions and estimated that a major burst of different transposable elements (TEs) occurred 21 million years ago. Notably, the timing of this TE burst coincided with the uplift of the Tian Shan mountains, which is thought to be the center of the location where the apple originated, suggesting that TEs and associated processes may have contributed to the diversification of the apple ancestor and possibly to its divergence from pear. Finally, genome-wide DNA methylation data suggest that epigenetic marks may contribute to agronomically relevant aspects, such as apple fruit development

Factors associated with low fitness in adolescents – A mixed methods study

Background: Fitness and physical activity are important for cardiovascular and mental health but activity and fitness levels are declining especially in adolescents and among girls. This study examines clustering of factors associated with low fitness in adolescents in order to best target public health interventions for young people. Methods: 1147 children were assessed for fitness, had blood samples, anthropometric measures and all data were linked with routine electronic data to examine educational achievement, deprivation and health service usage. Factors associated with fitness were examined using logistic regression, conditional trees and data mining cluster analysis. Focus groups were conducted with children in a deprived school to examine barriers and facilitators to activity for children in a deprived community. Results: Unfit adolescents are more likely to be deprived, female, have obesity in the family and not achieve in education. There were 3 main clusters for risk of future heart disease/diabetes (high cholesterol/insulin); children at low risk (not obese, fit, achieving in education), children ‘visibly at risk’ (overweight, unfit, many hospital/GP visits) and ‘invisibly at risk’ (unfit but not overweight, failing in academic achievement). Qualitative findings show barriers to physical activity include cost, poor access to activity, lack of core physical literacy skills and limited family support. Conclusions: Low fitness in the non-obese child can reveal a hidden group who have high risk factors for heart disease and diabetes but may not be identified as they are normal weight. In deprived communities low fitness is associated with non-achievement in education but in non-deprived communities low fitness is associated with female gender. Interventions need to target deprived families and schools in deprived areas with community wide campaigns

Compositional analysis of the associations between 24-h movement behaviours and cardio-metabolic risk factors in overweight and obese adults with pre-diabetes from the PREVIEW study : cross-sectional baseline analysis

Background Physical activity, sedentary time and sleep have been shown to be associated with cardio-metabolic health. However, these associations are typically studied in isolation or without accounting for the effect of all movement behaviours and the constrained nature of data that comprise a finite whole such as a 24 h day. The aim of this study was to examine the associations between the composition of daily movement behaviours (including sleep, sedentary time (ST), light intensity physical activity (LIPA) and moderate-to-vigorous activity (MVPA)) and cardio-metabolic health, in a cross-sectional analysis of adults with pre-diabetes. Further, we quantified the predicted differences following reallocation of time between behaviours. Methods Accelerometers were used to quantify daily movement behaviours in 1462 adults from eight countries with a body mass index (BMI) >= 25 kg center dot m(- 2), impaired fasting glucose (IFG; 5.6-6.9 mmol center dot l(- 1)) and/or impaired glucose tolerance (IGT; 7.8-11.0 mmol center dot l(- 1) 2 h following oral glucose tolerance test, OGTT). Compositional isotemporal substitution was used to estimate the association of reallocating time between behaviours. Results Replacing MVPA with any other behaviour around the mean composition was associated with a poorer cardio-metabolic risk profile. Conversely, when MVPA was increased, the relationships with cardiometabolic risk markers was favourable but with smaller predicted changes than when MVPA was replaced. Further, substituting ST with LIPA predicted improvements in cardio-metabolic risk markers, most notably insulin and HOMA-IR. Conclusions This is the first study to use compositional analysis of the 24 h movement composition in adults with overweight/obesity and pre-diabetes. These findings build on previous literature that suggest replacing ST with LIPA may produce metabolic benefits that contribute to the prevention and management of type 2 diabetes. Furthermore, the asymmetry in the predicted change in risk markers following the reallocation of time to/from MVPA highlights the importance of maintaining existing levels of MVPA.Peer reviewe

Feasibility and acceptability of a community pharmacy referral service for suspected lung cancer symptoms

Background Lung cancer survival rates in the UK are among the lowest in Europe, principally due to late-stage diagnosis. Alternative routes to earlier diagnosis of lung cancer are needed in socioeconomically deprived communities that are disproportionately affected by poor lung cancer outcomes. We assessed the feasibility and acceptability of a community-based pharmacy referral service to encourage earlier symptomatic referral for chest X-rays. Methods Seventeen community pharmacies located in a deprived area of Wales participated between March 2019 and March 2020. Stakeholder interviews were conducted with four patients, seven pharmacy professionals and one general practitioner. Four focus groups were conducted, including one with healthcare professionals (n=6) and three with members of the public who were current and former smokers (n=13). Quantitative data regarding patient characteristics and clinical outcomes were collected from hospital records and patient referral questionnaires completed by pharmacists and analysed using descriptive statistics. Qualitative data sets were analysed thematically and triangulated. Results Twelve patients used the pharmacy referral service, all of whom were male. Average length of the pharmacy consultation was 13 min, with a mean 3 days to accessing chest X-rays in secondary care. Patients experienced a mean 46-day wait for results, with no lung cancer detected. Participants found the service to be acceptable and considered the pharmacy element to be broadly feasible. Perceived barriers included low awareness of the service and concerns about the role and capacity of pharmacists to deliver the service. Facilitators included perceived approachability and accessibility of pharmacists. A well-publicised, multifaceted awareness campaign was recommended. Conclusions A community pharmacy referral service for lung symptoms was considered an acceptable alternative pathway to symptomatic diagnosis of lung cancer in deprived communities. Wider implementation of the service would require workforce capacity and training to be addressed to ensure optimum utilisation and promotion of the service