Innovative solution or cause for concern? The use of continuous glucose monitors in people not living with diabetes: A narrative review.

AIMS: Continuous glucose monitors (CGMs) have expanded their scope beyond indicated uses for diabetes management and are gaining traction among people not living with diabetes (PNLD). CGMs track in time glucose levels and are proposed as tools for the early detection of abnormal glucose and a potential solution for its normalisation through behavioural change, particularly, diet personalisation and motivation of physical activity. This becomes relevance given the growing incidence of metabolic conditions, such as type 2 diabetes mellitus (T2DM). Clinical guidelines, however, do not recommend CGMs in contexts outside type 1 diabetes (T1DM) or insulin-treated T2DM. Therefore, there is a visible disconnect between the indicated and real-world usage of these medical devices. While the commercial market for CGMs in PNLD is expanding rapidly, a comprehensive and evidence-based evaluation of the devices' utility in this population has not been done. Therefore, this review aims to formulate a working model for CGM utility in PNLD as proposed by the 'health and wellness' market that advertises and distributes it to these individuals. METHODS: We aim to critically analyse the available research addressing components of the working model, that is (1) detection of abnormal glucose; (2) behavioural change, and (3) metabolic health improvement. RESULTS: We find a lack of consistent and high-quality evidence to support the utility of CGMs for these purposes. We identify significantly under-reserved areas including clinical benchmarks and scoring procedures for CGM measures, device acceptability, and potential adverse effects of CGMs on eating habits in PNLD. We also raise concerns about the robustness of available CGM research. CONCLUSION: In the face of these research gaps, we urge for the commercial claims suggesting the utility of the device in PNLD to be labelled as misleading. We argue that there is a regulatory inadequacy that fuels 'off-label' CGM distribution and calls for the strengthening of post-market clinical follow-up oversight for CGMs. We hope this will help to avert the continued misinformation risk to PNLD and 'off-label' exacerbation of health disparities.

Nutrients or processing? An analysis of food and drink items from the UK National Diet and Nutrition Survey based on nutrient content, the NOVA classification and front of package traffic light labelling.

UK front of package labelling (FOPL) informs consumers on the nutrient content of food. However, FOPL does not consider food processing, and with the UK government being urged to act on ultra-processed food (UPF), whether UPF should be added to FOPL is unclear. This study compared food and drink in the UK National Diet and Nutrition Survey (NDNS) Intake24 database based on FOPL, nutrient content and NOVA classification, to understand whether UPF are covered by dietary recommendations for foods high in fat, salt and sugar. NDNS items were coded into minimally processed food (MPF), processed culinary ingredients, processed food and UPF according to the NOVA classification and FOPL traffic lights. UPF contained greater energy, fat, saturated fat (SF), total sugar (TS) and salt than MPF. UPF had a greater odds of containing red FOPL and an unhealthier overall FOPL score (OR:4·59 (95 % CI: 3·79, 5·57); OR:7·0 (95 % CI: 6·1, 8·2), respectively) and lower odds of containing green FOPL (OR:0·05 (95 % CI: 0·03, 0·10)), compared with MPFs. For items with no red FOPL, UPF still contained greater energy, fat, SF, TS and salt than MPF. However, several UPF have healthier FOPL scores. UPF had an unhealthier nutritional profile and FOPL score than MPF. For items with no red FOPL, UPF still had an unhealthier profile than MPF, with a higher energy density. Importantly, not all UPF were unhealthy according to FOPL. These results indicate partial overlap between FOPL, nutrient content and NOVA classification of UK food and drink products, with implications for UK food and drink labelling.

The impact of the cost of living crisis and food insecurity on food purchasing behaviours and food preparation practices in people living with obesity.

Lower income households are at greater risk of food insecurity and poor diet quality than higher income households. In high-income countries, food insecurity is associated with high levels of obesity, and in the UK specifically, the cost of living crisis (i.e., where the cost of everyday essentials has increased quicker than wages) is likely to have exacerbated existing dietary inequalities. There is currently a lack of understanding of the impact of the current UK cost of living crisis on food purchasing and food preparation practices of people living with obesity (PLWO) and food insecurity, however this knowledge is critical in order to develop effective prevention and treatment approaches to reducing dietary inequalities. Using an online survey (N = 583) of adults residing in England or Scotland with a body mass index (BMI) of ≥30 kg/m2, participants self-reported on food insecurity, diet quality, perceived impact of the cost of living crisis, and their responses to this in terms of food purchasing behaviours and food preparation practices. Regression analyses found that participants adversely impacted by the cost of living crisis reported experiencing food insecurity. Additionally, food insecurity was associated with use of specific purchasing behaviours (i.e., use of budgeting, use of supermarket offers) and food preparation practices (i.e., use of energy-saving appliances, use of resourcefulness). Exploratory analyses indicated that participants adversely impacted by the cost of living crisis and who used budgeting had low diet quality, whereas use of meal planning was associated with high diet quality. These findings highlight the fragility of food budgets and the coping strategies used by PLWO and food insecurity during the cost of living crisis. Policy measures and interventions are urgently needed that address the underlying economic factors contributing to food insecurity, to improve access to and affordability of healthier foods for all.

'My words would have more weight': exploring weight stigma in UK dietetic practice and dietitian's lived experiences of weight stigma.

BACKGROUND: Weight stigma is pervasive within healthcare and negatively impacts both access to care and the patient-practitioner relationship. There is limited evidence on weight stigma among registered dietitians, particularly in the United Kingdom, though data show weight-related prejudice towards people living with obesity. The aim of this study was to examine both explicit and implicit weight stigma in practicing dietitians in the United Kingdom, as well as the lived experience of weight stigma among dietitians, both towards themselves and towards others. METHODS: An online cross-sectional survey was disseminated between February and May 2022 using snowball sampling. Inclusion criteria were that participants were UK registered dietitians aged 20-70 years. RESULTS: Four hundred and two dietitians responded to the survey (female [94.1%], mean age 40.2 years [standard deviation (SD) 10.7]; White ethnicity [90%]; median 12 years [interquartile range (IQR) 6, 22] within dietetic practice). Mean self-reported body mass index was 25.1 kg/m² (SD 8.7). Most dietitians reported experiencing weight stigma prior to (51%) and postregistration (59.7%), whereas nearly a quarter (21.1%) felt that weight influenced their ability as a dietitian. Weight stigma was experienced across the weight spectrum. Overall participants reported explicit weight bias attitudes, moderate beliefs that obesity is controllable and implicit antifat bias. Within open-ended responses, dietitians reported three key themes related to their personal experiences of weight stigma: (1) experiences of stigma in dietetic practice, (2) impact of weight stigma and (3) perception of weight, appearance and job. CONCLUSION: This study shows that UK dietitians exhibit both explicit and implicit weight bias towards people living with obesity. Dietitians reported experiencing weight stigma, which impacted their career-related decisions and their perception of their own ability to perform as dietitians. The study highlights the need to address weight stigma and its implications within the dietetic profession.

Systematic review of the barriers and facilitators to dietary modification in people living with type 2 diabetes and pre-diabetes from South Asian ethnic populations.

AIMS: Lifestyle and dietary modification are effective in the prevention and management of Type 2 diabetes Mellitus (T2DM). However, South Asian (SA) populations living in Western countries have low adherence rates to healthcare advice and experience poor diabetes control and clinical outcomes compared with the general population. This systematic review aimed to summarise the barriers and facilitators of dietary modification within people from South Asian (SA) ethnicity with T2DM or pre-diabetes. METHODS: A systematic search of PubMed, Web of Science and Scopus generated 3739 articles, of which seven were included. Qualitative and quantitative data were inputted utilising COVIDENCE. Qualitative data were analysed by thematic analysis. RESULTS: Thematic analysis identified three facilitators: (1) cultural sensitivity, (2) health education and (3) support networks. Barriers include (1) healthcare inequity, (2) cultural insensitivity, (3) social pressures, (4) misconceptions and (5) time constraints. Good access to health care and motivation were the most common facilitators discussed. Misconceptions on T2DM management and cultural insensitivity contributed to the majority of barriers discussed. CONCLUSIONS: Culturally tailored interventions could improve adherence to diet modification in people with T2DM from SA ethnicity. Interventions involving the application of social media to challenge intergenerational stigmas and misinformation, distributing culturally appropriate resources and providing diets tailored to the SA palate could help.

Heterologous production of the insecticidal pea seed albumin PA1 protein by Pichia pastoris and protein engineering to potentiate aphicidal activity via fusion to snowdrop lectin Galanthus nivalis agglutinin; GNA).

BACKGROUND: New bioinsecticides with novel modes of action are urgently needed to minimise the environmental and safety hazards associated with the use of synthetic chemical pesticides and to combat growing levels of pesticide resistance. The pea seed albumin PA1b knottin peptide is the only known proteinaceous inhibitor of insect vacuolar adenosine triphosphatase (V-ATPase) rotary proton pumps. Oral toxicity towards insect pests and an absence of activity towards mammals makes Pa1b an attractive candidate for development as a bioinsecticide. The purpose of this study was to investigate if Pichia pastoris could be used to express a functional PA1b peptide and if it's insecticidal activity could be enhanced via engineering to produce a fusion protein comprising the pea albumin protein fused to the mannose-specific snowdrop lectin (Galanthus nivalis agglutinin; GNA). RESULTS: We report the production of a recombinant full-length pea albumin protein (designated PAF) and a fusion protein (PAF/GNA) comprised of PAF fused to the N-terminus of GNA in the yeast Pichia pastoris. PAF was orally toxic to pea (Acyrthosiphon pisum) and peach potato (Myzus persicae) aphids with respective, Day 5 LC50 values of 54 µM and 105 µM derived from dose-response assays. PAF/GNA was significantly more orally toxic as compared to PAF, with LC50 values tenfold (5 µM) and 3.3-fold (32 µM) lower for pea and peach potato aphids, respectively. By contrast, no phenotypic effects were observed for worker bumble bees (Bombus terristrus) fed PAF, GNA or PAF/GNA in acute toxicity assays. Confocal microscopy of pea aphid guts after pulse-chase feeding fluorescently labelled proteins provides evidence that enhanced efficacy of the fusion protein is attributable to localisation and retention of PAF/GNA to the gut epithelium. In contact assays the fusion protein was also found to be significantly more toxic towards A. pisum as compared to PAF, GNA or a combination of the two proteins. CONCLUSIONS: Our results suggest that GNA mediated binding to V-type ATPase pumps acts to potentiate the oral and contact aphicidal activity of PAF. This work highlights potential for the future commercial development of plant protein-based bioinsecticides that offer enhanced target specificity as compared to chemical pesticides, and compatibility with integrated pest management strategies.

The impact of living through COVID-19 pandemic on mental health, food insecurity, loneliness and health behaviours in people with obesity.

BACKGROUND: The COVID-19 pandemic has negatively impacted people living with obesity. The aim was to examine the continued impact of the COVID-19 pandemic on the mental health of people living with obesity and associations with food insecurity, loneliness and health-related behaviours. METHODS: The study recruited 1187 UK adults living with obesity who completed an online survey, which examined mental health and associations with food insecurity, loneliness and health-related behaviours from July 2020 (end of the first lockdown in the United Kingdom) to the point they completed the survey in 2021. Regression analyses were used to examine relationships between outcome variables and demographic factors, and hierarchical linear regression models were used to assess levels of loneliness, depression and well-being. RESULTS: Participants reported worse loneliness, depression, well-being and food insecurity compared to pre-COVID. However, participants reported attempting to lose weight, healthier food shopping, diet and increased physical activity. Quality and quantity of sleep deteriorated compared to prior to COVID-19. CONCLUSIONS: Adults living with obesity in the United Kingdom report a continued negative impact of the COVID-19 pandemic upon their mental health together with increased loneliness and food insecurity. However, our findings suggest that UK adults living with obesity have increased their engagement in positive health behaviours and were attempting to lose weight.

Isolation of Arabidopsis extracellular ATP binding proteins by affinity proteomics and identification of PHOSPHOLIPASE C-LIKE 1 as an extracellular protein essential for fumonisin B1 toxicity.

ATP is secreted to the extracellular matrix, where it activates plasma membrane receptors for controlling plant growth and stress-adaptive processes. DOES NOT RESPOND TO NUCLEOTIDES 1 (DORN1), was the first plant ATP receptor to be identified but key downstream proteins remain sought after. Here, we identified 120 proteins secreted by Arabidopsis cell cultures and screened them for putative stress-responsive proteins using ATP-affinity purification. We report three Arabidopsis proteins isolated by ATP-affinity: PEROXIDASE 52, SUBTILASE-LIKE SERINE PROTEASE 1.7 and PHOSPHOLIPASE C-LIKE 1. In wild-type Arabidopsis, the expression of genes encoding all three proteins responded to fumonisin B1, a cell death-activating mycotoxin. The expression of PEROXIDASE 52 and PHOSPHOLIPASE C-LIKE 1 was altered in fumonisin B1-resistant salicylic acid induction-deficient (sid2) mutants. Exposure to fumonisin B1 suppressed PHOSPHOLIPASE C-LIKE 1 expression in sid2 mutants, suggesting that the inactivation of this gene might provide mycotoxin tolerance. Accordingly, gene knockout mutants of PHOSPHOLIPASE C-LIKE 1 were resistant to fumonisin B1-induced death. The activation of PHOSPHOLIPASE C-LIKE 1 gene expression by exogenous ATP was not blocked in dorn1 loss-of-function mutants, indicating that DORN1 is not required. Furthermore, exogenous ATP rescued both the wild type and the dorn1 mutants from fumonisin-B1 toxicity, suggesting that different ATP receptor(s) are operational in this process. Our results point to the existence of additional plant ATP receptor(s) and provide crucial downstream targets for use in designing screens to identify these receptors. Finally, PHOSPHOLIPASE C-LIKE 1 serves as a convergence point for fumonisin B1 and extracellular ATP signalling, and functions in the Arabidopsis stress response to fumonisin B1.

Perceived weight-related stigma, loneliness, and mental wellbeing during COVID-19 in people with obesity: A cross-sectional study from ten European countries.

BACKGROUND: Increased weight-related stigma during the COVID-19 pandemic has amplified the need to minimise the impacts on mental wellbeing. We investigated the relationship between the perceived changes in the representation of obesity in the media and mental wellbeing during the pandemic in a sample of people with obesity across 10 European countries. We also investigated the potential moderating effect of loneliness. METHODS: Between September to December 2020 during the COVID-19 pandemic, participants reported data on demographics, mental wellbeing (measured by World Health Organisation Five Wellbeing Index and Patient Health Questionaire-4), loneliness (measured by De Jong Gierveld short scale), and perceived change in the representation of obesity in media (measured by a study-specific question) using the online, cross-sectional EURopean Obesity PatiEnt pANdemic Survey (EUROPEANS). Data were analysed using linear mixed-effects models, controlling for age, gender, body mass index, and shielding status, with random incept for country. RESULTS: The survey was completed by 2882 respondents. Most identified as female (56%) and reported their ethnicity as White or White-mix (92%). The total sample had a mean age of 41 years and a BMI of 35.4 kg/m2. During the peak of the pandemic, compared to pre-pandemic, perceiving more negative representation of people with obesity on social media was associated with worse psychological distress, depression, and wellbeing. Perceiving more positive representation, compared to no change in representation, of people with obesity on television was associated with greater wellbeing, yet also higher psychological distress and anxiety. Loneliness, as a moderator, explained ≤0.3% of the variance in outcomes in any of the models. CONCLUSIONS: Perceiving negative representation of obesity on social media was associated with poorer mental wellbeing outcomes during the pandemic; positive representation on television was associated with both positive and negative mental wellbeing outcomes. We encourage greater media accountability when representing people with obesity.

A blinded evaluation of privacy preserving record linkage with Bloom filters.

BACKGROUND: Privacy preserving record linkage (PPRL) methods using Bloom filters have shown promise for use in operational linkage settings. However real-world evaluations are required to confirm their suitability in practice. METHODS: An extract of records from the Western Australian (WA) Hospital Morbidity Data Collection 2011-2015 and WA Death Registrations 2011-2015 were encoded to Bloom filters, and then linked using privacy-preserving methods. Results were compared to a traditional, un-encoded linkage of the same datasets using the same blocking criteria to enable direct investigation of the comparison step. The encoded linkage was carried out in a blinded setting, where there was no access to un-encoded data or a 'truth set'. RESULTS: The PPRL method using Bloom filters provided similar linkage quality to the traditional un-encoded linkage, with 99.3% of 'groupings' identical between privacy preserving and clear-text linkage. CONCLUSION: The Bloom filter method appears suitable for use in situations where clear-text identifiers cannot be provided for linkage.

Dietary strategies for remission of type 2 diabetes: A narrative review.

Type 2 diabetes (T2DM) is a growing health issue globally, which, until recently, was considered to be both chronic and progressive. Although having lifestyle and dietary changes as core components, treatments have focused on optimising glycaemic control using pharmaceutical agents. With data from bariatric surgery and, more recently, total diet replacement (TDR) studies that have set out to achieve remission, remission of T2DM has emerged as a treatment goal. A group of specialist dietitians and medical practitioners was convened, supported by the British Dietetic Association and Diabetes UK, to discuss dietary approaches to T2DM and consequently undertook a review of the available clinical trial and practice audit data regarding dietary approaches to remission of T2DM. Current available evidence suggests that a range of dietary approaches, including low energy diets (mostly using TDR) and low carbohydrate diets, can be used to support the achievement of euglycaemia and potentially remission. The most significant predictor of remission is weight loss and, although euglycaemia may occur on a low carbohydrate diet without weight loss, which does not meet some definitions of remission, it may rather constitute a 'state of mitigation' of T2DM. This technical point may not be considered as important for people living with T2DM, aside from that it may only last as long as the carbohydrate restriction is maintained. The possibility of actively treating T2DM along with the possibility of achieving remission should be discussed by healthcare professionals with people living with T2DM, along with a range of different dietary approaches that can help to achieve this.

The importance of the epithelial fibre cell interface to lens regeneration in an in vivo rat model and in a human bag-in-the-lens (BiL) sample.

Human lens regeneration and the Bag-in-the-Lens (BIL) surgical treatment for cataract both depend upon lens capsule closure for their success. Our studies suggest that the first three days after surgery are critical to their long-term outcomes. Using a rat model of lens regeneration, we evidenced lens epithelial cell (LEC) proliferation increased some 50 fold in the first day before rapidly declining to rates observed in the germinative zone of the contra-lateral, un-operated lens. Cell multi-layering at the lens equator occurred on days 1 and 2, but then reorganised into two discrete layers by day 3. E- and N-cadherin expression preceded cell polarity being re-established during the first week. Aquaporin 0 (AQP0) was first detected in the elongated cells at the lens equator at day 7. Cells at the capsulotomy site, however, behaved very differently expressing the epithelial mesenchymal transition (EMT) markers fibronectin and alpha-smooth muscle actin (SMA) from day 3 onwards. The physical interaction between the apical surfaces of the anterior and posterior LECs from day 3 after surgery preceded cell elongation. In the human BIL sample fibre cell formation was confirmed by both histological and proteome analyses, but the cellular response is less ordered and variable culminating in Soemmerring's ring (SR) formation and sometimes Elschnig's pearls. This we evidence for lenses from a single patient. No bow region or recognisable epithelial-fibre cell interface (EFI) was evident and consequently the fibre cells were disorganised. We conclude that lens cells require spatial and cellular cues to initiate, sustain and produce an optically functional tissue in addition to capsule integrity and the EFI.

Reductive Stress Selectively Disrupts Collagen Homeostasis and Modifies Growth Factor-independent Signaling Through the MAPK/Akt Pathway in Human Dermal Fibroblasts.

Redox stress is a well-known contributor to aging and diseases in skin. Reductants such as dithiothreitol (DTT) can trigger a stress response by disrupting disulfide bonds. However, the quantitative response of the cellular proteome to reductants has not been explored, particularly in cells such as fibroblasts that produce extracellular matrix proteins. Here, we have used a robust, unbiased, label-free SWATH-MS proteomic approach to quantitate the response of skin fibroblast cells to DTT in the presence or absence of the growth factor PDGF. Of the 4487 proteins identified, only 42 proteins showed a statistically significant change of 2-fold or more with reductive stress. Our proteomics data show that reductive stress results in the loss of a small subset of reductant-sensitive proteins (including the collagens COL1A1/2 and COL3A1, and the myopathy-associated collagens COL6A1/2/3), and the down-regulation of targets downstream of the MAPK pathway. We show that a reducing environment alters signaling through the PDGF-associated MAPK/Akt pathways, inducing chronic dephosphorylation of ERK1/2 at Thr202/Tyr204 and phosphorylation of Akt at Ser473 in a growth factor-independent manner. Our data highlights collagens as sentinel molecules for redox stress downstream of MAPK/Akt, and identifies intervention points to modulate the redox environment to target skin diseases and conditions associated with erroneous matrix deposition.

Examining Cesarean Section Rates in Canada Using the Modified Robson Classification.

OBJECTIVE: Canada's cesarean delivery (CD) rate continues to increase. The Society of Obstetricians and Gynaecologists of Canada advocates the use of the modified Robson classification for comparisons. This study describes national and provincial CD rates according to this classification system. METHODS: All 2016-2017 in-hospital births in Canada (outside Québec) reported to the Discharge Abstract Database were categorized using the modified Robson classification system. CD rates, group size, and contributions of each group to the overall volume of CD were reported. Rates by province and hospital peer group were also examined (Canadian Task Force Classification III). RESULTS: A total of 286 201 women gave birth; among these, 83 262 (29.1%) had CDs. Robson group 5 (term singleton previous CD) had a CD rate of 80.5% and was the largest contributing group to the overall number of CD (36.6%). Women whose labour was induced (Robson group 2A) had a CD rate almost double the rate of women with spontaneous labour (Robson group 1): 33.5% versus 18.4%. These latter two groups made the next largest contributions to overall CD (15.7% and 14.1%, respectively). There were substantial variations in CD rates across provinces and among hospital peer groups. CONCLUSION: The study found large variations in CD rates across provinces and hospitals within each Robson group, thus suggesting that examining variations to determine the groups contributing the most to CD rates (Robson groups 5, 2A, and 1) may provide valuable insight for reducing CD rates. This study provides a benchmark for measuring the impact of future initiatives to reduce CD rates in Canada.

Evaluation of a novel vital sign device to reduce maternal mortality and morbidity in low-resource settings: a mixed method feasibility study for the CRADLE-3 trial.

BACKGROUND: The CRADLE-3 trial is a stepped-wedge randomised controlled trial aiming to reduce maternal mortality and morbidity by implementing a novel vital sign device (CRADLE Vital Sign Alert) and training package into routine maternity care in 10 low-income sites. The MRC Guidance on complex interventions proposes that interventions and implementation strategies be shaped by early phase piloting and development work. We present the findings of a three-month mixed-methodology feasibility study for this trial, describe how this was informed by the MRC guidance and the study design was refined. METHODS: The fidelity, dose, feasibility and acceptability of implementation and training materials were assessed in three representative non-trial sites (Zimbabwe, Ethiopia, India) using multiple-choice questionnaires, evaluation of clinical management (action log), healthcare provider (HCP) semi-structured interviews and focus groups 4-10 weeks after implementation. Simultaneously, the 10 sites included in the main trial (eight countries) collected primary outcome data to inform the power calculation and randomisation allocation and assess the feasibility of data collection. RESULTS: The package was implemented with high fidelity (85% of HCP trained, n = 204). The questionnaires indicated a good understanding of device use with 75% of participants scoring > 75% (n = 97; 90% of those distributed). Action logs were inconsistently completed but indicated that the majority of HCP responded appropriately to abnormal results. From 18 HCP interviews and two focus groups it was widely reported that the intervention improved capacity to make clinical decisions, escalate care and make appropriate referrals. Nine of the ten main trial sites achieved ethical approval for pilot data collection. Intensive care was an inconsistent marker of morbidity and stroke an infrequent outcome and therefore they were removed from the main trial composite outcome. Tools and methods of data collection were optimized and event rates used to inform randomisation. CONCLUSIONS: This feasibility study demonstrates that the components of the intervention were acceptable, methods of implementing were successful and the main trial design would be feasible. Qualitative work identified key moderators that informed the main trial process evaluation. Changes to the training package, implementation strategy, study design and processes were identified to refine the implementation in the main trial. TRIAL REGISTRATION: ISRCTN41244132 ; Registered 24/11/2015.

Sociodemographic differences in linkage error: an examination of four large-scale datasets.

BACKGROUND: Record linkage is an important tool for epidemiologists and health planners. Record linkage studies will generally contain some level of residual record linkage error, where individual records are either incorrectly marked as belonging to the same individual, or incorrectly marked as belonging to separate individuals. A key question is whether errors in linkage quality are distributed evenly throughout the population, or whether certain subgroups will exhibit higher rates of error. Previous investigations of this issue have typically compared linked and un-linked records, which can conflate bias caused by record linkage error, with bias caused by missing records (data capture errors). METHODS: Four large administrative datasets were individually de-duplicated, with results compared to an available 'gold-standard' benchmark, allowing us to avoid methodological issues with comparing linked and un-linked records. Results were compared by gender, age, geographic remoteness (major cities, regional or remote) and socioeconomic status. RESULTS: Results varied between datasets, and by sociodemographic characteristic. The most consistent findings were worse linkage quality for younger individuals (seen in all four datasets) and worse linkage quality for those living in remote areas (seen in three of four datasets). The linkage quality within sociodemographic categories varied between datasets, with the associations with linkage error reversed across different datasets due to quirks of the specific data collection mechanisms and data sharing practices. CONCLUSIONS: These results suggest caution should be taken both when linking younger individuals and those in remote areas, and when analysing linked data from these subgroups. Further research is required to determine the ramifications of worse linkage quality in these subpopulations on research outcomes.

SUMO Is a Critical Regulator of Salt Stress Responses in Rice.

SUMO (Small Ubiquitin-like Modifier) conjugation onto target proteins has emerged as a very influential class of protein modification systems. SUMO1/2 double mutant plants are nonviable, underlining the importance of SUMO conjugation to plant survival. Once covalently bound, SUMO can alter a conjugated protein's stability and/or function. SUMO conjugation is a highly dynamic process that can be rapidly reversed by the action of SUMO proteases. The balance between the conjugated/deconjugated forms is a major determinant in the modulation of SUMO-target function. Despite the important mechanistic role of SUMO proteases in model plants, until now the identity or the function of these regulatory enzymes has not been defined in any crop plant. In this report, we reveal the ubiquitin-like protease class of SUMO protease gene family in rice (Oryza sativa) and demonstrate a critical role for OsOTS1 SUMO protease in salt stress. OsOTS-RNAi rice plants accumulate high levels of SUMO-conjugated proteins during salt stress and are highly salt sensitive; however, in non-salt conditions, they are developmentally indistinguishable from wild-type plants. Transgenic rice plants overexpressing OsOTS1 have increased salt tolerance and a concomitant reduction in the levels of SUMOylated proteins. We demonstrate that OsOTS1 confers salt tolerance in rice by increasing root biomass. High salinity triggers OsOTS1 degradation, indicating that increased SUMO conjugation in rice plants during salt stress is in part achieved by down-regulation of OTS1/2 activity. OsOTS1 is nuclear localized indicating a direct requirement of OsOTS1-dependent deSUMOylation activity in rice nuclei for salt tolerance.

Insulin-associated weight gain in obese type 2 diabetes mellitus patients: What can be done?

Insulin therapy (IT) is initiated for patients with type 2 diabetes mellitus when glycaemic targets are not met with diet and other hypoglycaemic agents. The initiation of IT improves glycaemic control and reduces the risk of microvascular complications. There is, however, an associated weight gain following IT, which may adversely affect diabetic and cardiovascular morbidity and mortality. A 3 to 9 kg insulin-associated weight gain (IAWG) is reported to occur in the first year of initiating IT, predominantly caused by adipose tissue. The potential causes for this weight gain include an increase in energy intake linked to a fear of hypoglycaemia, a reduction in glycosuria, catch-up weight, and central effects on weight and appetite regulation. Patients with type 2 diabetes who are receiving IT often have multiple co-morbidities, including obesity, that are exacerbated by weight gain, making the management of their diabetes and obesity challenging. There are several treatment strategies for patients with type 2 diabetes, who require IT, that attenuate weight gain, help improve glycaemic control, and help promote body weight homeostasis. This review addresses the effects of insulin initiation and intensification on IAWG, and explores its potential underlying mechanisms, the predictors for this weight gain, and the available treatment options for managing and limiting weight gain.

Estimating parameters for probabilistic linkage of privacy-preserved datasets.

BACKGROUND: Probabilistic record linkage is a process used to bring together person-based records from within the same dataset (de-duplication) or from disparate datasets using pairwise comparisons and matching probabilities. The linkage strategy and associated match probabilities are often estimated through investigations into data quality and manual inspection. However, as privacy-preserved datasets comprise encrypted data, such methods are not possible. In this paper, we present a method for estimating the probabilities and threshold values for probabilistic privacy-preserved record linkage using Bloom filters. METHODS: Our method was tested through a simulation study using synthetic data, followed by an application using real-world administrative data. Synthetic datasets were generated with error rates from zero to 20% error. Our method was used to estimate parameters (probabilities and thresholds) for de-duplication linkages. Linkage quality was determined by F-measure. Each dataset was privacy-preserved using separate Bloom filters for each field. Match probabilities were estimated using the expectation-maximisation (EM) algorithm on the privacy-preserved data. Threshold cut-off values were determined by an extension to the EM algorithm allowing linkage quality to be estimated for each possible threshold. De-duplication linkages of each privacy-preserved dataset were performed using both estimated and calculated probabilities. Linkage quality using the F-measure at the estimated threshold values was also compared to the highest F-measure. Three large administrative datasets were used to demonstrate the applicability of the probability and threshold estimation technique on real-world data. RESULTS: Linkage of the synthetic datasets using the estimated probabilities produced an F-measure that was comparable to the F-measure using calculated probabilities, even with up to 20% error. Linkage of the administrative datasets using estimated probabilities produced an F-measure that was higher than the F-measure using calculated probabilities. Further, the threshold estimation yielded results for F-measure that were only slightly below the highest possible for those probabilities. CONCLUSIONS: The method appears highly accurate across a spectrum of datasets with varying degrees of error. As there are few alternatives for parameter estimation, the approach is a major step towards providing a complete operational approach for probabilistic linkage of privacy-preserved datasets.