Adapting an online guided self- help intervention for the management of binge eating in adults with type 2 diabetes: The POSE- D study

Aims People with type 2 diabetes (T2D) are more likely to experience binge eating than the general population, which may interfere with their diabetes management. Guided self-help (GSH) is the recommended treatment for binge-eating disorder, but there is currently a lack of evidenced treatment for binge eating in individuals living with T2D. The aims of the current study were to adapt an existing evidence-based GSH intervention using the principles of co-design to make it available online, suitable for remote delivery to address binge eating specifically in adults living with T2D. The Working to Overcome Eating Difficulties GSH intervention comprises online GSH materials presented in seven sections delivered over 12 weeks, supported by a trained Guide. Methods In order to adapt the intervention, we held four collaboration workshops with three expert patients recruited from diabetes support groups, eight healthcare professionals and an expert consensus group. We used thematic analysis to make sense of the data. Results and Conclusions The main themes included; keeping the GSH material generic, adapting Sam the central character, tailoring the dietary advice and eating diary. The length of Guidance sessions was increased to 60 min, and Guide training was focussed around working with people with diabetes

Архетип свобода у контексті французької політичної теорії та історії

Розглянуто сучасні підходи щодо аналізу політичної ментальності. У межах політологічного аналізу окреслено коло проблем, які потребують вирішення з використанням підходів психології. Зроблено висновок про те, що архетип “свобода” становить важливий елемент політичної ментальності французів.Modern approaches of analysis of political mentality are considered. Within the limits of political science analysis outlined circle of problems which need decision with the use of approaches of psychology. A conclusion is done that archetype freedom makes the important element of political mentality of French’s

Personal characteristics influence rapid-acting insulin pharmacokinetics in individuals with type 1 diabetes treated with multiple daily injections [Conference abstract]

Background and aims: The pharmacokinetics and pharmacodynamics of the rapid-acting insulin analogues aspart and lispro have been wellcharacterised and are considered comparable, with analogues displaying similarly large inter-personal variability in action-time profiles following subcutaneous injection. However, it is unknown whether, and which, personal characteristics explain inter-personal variability in rapid-acting insulin kinetics. Therefore, we compared serum insulin kinetics following subcutaneous injection of prandially-administered rapid-acting insulin in people with type 1 diabetes (T1D) treated on multiple daily injections. Materials and methods: Thirty-two individuals (mean±SD: 31±6.89 years, 26.03±4.82 kg/m2 ) with T1D, treated with multiple daily injections consisting of rapid-acting insulins aspart (n=20) and lispro (n=12), and basal-insulins glargine (n=23) and detemir (n=9) were recruited. Subjects attended the laboratory on a single morning (~8am) following an overnight fast and self-administered a subcutaneous dose of rapid-acting insulin to the lower abdomen immediately before the consumption of a standardised meal. Rapid-acting insulin doses were standardised and calculated using the carbohydrate counting method; basal insulin remained unchanged. Serum insulin levels were measured for 6-hours following administration. Regression analysis was used to assess associations between serum insulin kinetics and personal characteristics. Results: Serum insulin AUC was positively associated with age (p=0.006, 95%CI -85.6 to -15.9), duration of diabetes (p<0.001, 95%CI -70.1 to - 22.6), HbA1c (p=0.001, CI -71.4 to -12.0), BMI (p=0.006, 95%CI -120.3 to -19.8), and circulating fibrinogen concentrations (p=0.002, 95%CI -0.50 to -0.12) and negatively associated with estimated glucose disposal rate (eGDR; p=0.008, 95%CI 51.4 to 231.8). Bolus dose was positively associated with age (p<0.001, 95%CI 0.141 to 0.384), duration of diabetes (p<0.001, 95%CI 0.092 to 0.278), HbA1c (p=0.001, 95%CI 0.088 to 0.287), and BMI (p<0.001, 95%CI 0.210 to 0.553) and negatively associated with eGDR (p=0.002; 95%CI -0.938 to -0.243), but not serum insulin AUC, iAUC, peak, or time to peak (p>0.05). Conclusion: We show for the first time that inter-personal variability in rapid-acting insulin kinetics are influenced by personal characteristics including age, diabetes duration, HbA1c, BMI, eGDR, and circulating fibrinogen concentrations in people with T1D. These data yield important implications for determining patient-specific rapid-acting insulin dosing recommendations which could lead to more effective self-management strategie

Interrupted sitting improves acute postprandial glucose control without increasing risk of hypoglycaemia in people with type 1 diabetes [Conference abstract]

Background and aims: We have previously shown that interrupting prolonged periods of sitting with short, frequent light-intensity walking activity improves postprandial glucose levels in people with and at risk of Type 2 Diabetes. However, no research has investigated whether and how such an intervention affects postprandial glucose control, including the risk of hypoglycaemia, in people with Type 1 Diabetes (T1D). Therefore, we assessed the impact of short, frequent bouts of light-intensity walking on acute postprandial glycaemia in people with T1D. Materials and methods: In a randomised crossover design, ten inactive adults with T1D (6 men; mean±SD: 30±34.7 years) completed two fasted morning-time (~08:00am) laboratory visits each separated by a minimum of a 1-week washout. On each occasion participants consumed a standardised carbohydrate-based meal with their usual insulin dose determined by the carbohydrate-counting method; the meal and insulin dose was identical on each occasion. Following consumption of the meal, participants underwent two experimental conditions each lasting 4-hours: (1) uninterrupted sitting (SIT); or (2) sitting interrupted with 5-minute bouts of self-paced light-intensity walking every 30-minutes for a total of 4-hours (SIT-Less). Interstitial glucose responses were measured across the 4-hour postprandial period using continuous glucose monitoring (CGM). Results: Postprandial glucose concentrations increased with SIT whereas this rise was tempered with SIT-Less (SIT: Δ2.7±2.6 vs. SIT-Less Δ0.4±1.2 mmol/L p=.043). With SIT-Less, Time in Range (3.9-10 mmol/L) was significantly increased (SIT 114±114 vs. SIT-Less 288±36 minutes p=.008), time spent in hyperglycaemia was significantly reduced (SIT 94±86 vs. SIT-Less 9.5±24 minutes, p=.043), and glucose peak was significantly lower (SIT: Δ5.8±4.1 vs. SIT-Less 2.0±1.4 mmol/L p=.047). There were no episodes of hypoglycaemia in either condition. Conclusion: Interrupting sitting time, with brief regular bouts of light-intensity walking activity, significantly improves acute postprandial glycaemia in people with T1D without increasing the risk of acute hypoglycaemia. With low adherence to structured exercise and the ubiquity of sedentary behaviours, these preliminary findings suggest that interrupted sitting has the potential to be a safe, beneficial and practical means for improving postprandial glycaemia in people with T1D

Interrupted sitting improves 24-hour glucose control in people with type 1 diabetes [Conference abstract]

Background and aims: Interrupting prolonged periods of sitting with short, frequent light-intensity walking improves 24-hour glucose control Diabetologia in people with and at risk of Type 2 Diabetes. However, it is unknown whether and how such an intervention influences 24-hour glucose control, including risk of hypoglycaemia, in people with Type 1 Diabetes (T1D). Therefore, we evaluated the effect of short, frequent bouts of light-intensity walking on 24-hour glycaemia in people with T1D. Materials and methods: In a randomised crossover design, ten inactive adults with T1D (6 men; mean±SD: 30±34.7 years) completed two morning (~08:00am) laboratory visits in a fasted state, each separated by at least 1-week. On both visits, participants consumed a standardised carbohydrate-based meal with their usual insulin dose determined by the carbohydrate-counting method; the meal and insulin dose were identical on each visit. After consuming the meal, participants underwent two experimental conditions: (1) uninterrupted sitting (SIT); or (2) sitting interrupted with 5-minute bouts of light-intensity walking every 30- minutes for 4-hours (SIT-Less). Interstitial glucose responses were measured using continuous glucose monitoring (CGM) during the 4- hour laboratory visit for a further 20-hours under free-living conditions. Results: Compare to SIT, whole-day glycaemia was significantly lower following SIT-Less; 24-hour interstitial glucose Area Under the Curve was -14%[1.2%] under SIT-Less (p=0.023), accompanied by a significantly smaller average change in interstitial glucose from baseline (SIT: Δ1.5±2.5 vs. SIT-Less Δ-0.01±1.6 mmol/L, p=0.001), and lower average interstitial glucose peak (SIT:Δ7.7±3.0 vs. SIT-Less Δ3.9±1.4 mmol/L, p=0.002). Furthermore, with SIT-Less, Time in Range (TIR; 3.9-10 mmol/L), was significantly greater (TIR: SIT 991.5±286.86 vs. SIT-Less 1240.5±173.5 minutes, p=0.030), while time spent in hyperglycaemia was significantly lower (SIT 413.5±266.8 vs. SIT-Less 162±163.6 minutes, p=0.020). However, time spent in hypoglycaemia was similar between conditions (SIT 35±68.68 vs. SIT-Less 37.5±62.19 minutes, p=0.933). Glycaemic variability was lower with SIT-Less (CV%: SIT 29.4±7.6 vs. SIT-Less 22.1±7.5 %, p=0.021). Conclusion: Interrupting sitting time, with brief light-intensity walking activity, significantly improves whole-day glucose control in people with T1D. These preliminary findings suggest that interrupted sitting may serve as an effective and practical means of normalising daily glucose levels in people with T1D by increasing time in range and reducing glycaemic variability, without increasing the risk of hypoglycaemia

Epitope Mapping by Epitope Excision, Hydrogen/Deuterium Exchange, and Peptide-Panning Techniques Combined with In Silico Analysis

The fine characterization of protective B cell epitopes plays a pivotal role in the development of novel vaccines. The development of epitope-based vaccines, in fact, cannot be possible without a clear definition of the antigenic regions involved in the binding between the protective antibody (Ab) and its molecular target. To achieve this result, different epitope-mapping approaches have been widely described (Clementi et al. Drug Discov Today 18(9-10):464-471, 2013). Nowadays, the best way to characterize an Ab bound region is still the resolution of Ab-antigen (Ag) co-crystal structure. Unfortunately, the crystallization approaches are not always feasible. However, different experimental strategies aimed to predict Ab-Ag interaction and followed by in silico analysis of the results may be good surrogate approaches to achieve this result. Here, we review few experimental techniques followed by the use of "basic" informatics tools for the analysis of the results

DNA Binding Restricts the Intrinsic Conformational Flexibility of Methyl CpG Binding Protein 2 (MeCP2)*

Mass spectrometry-based hydrogen/deuterium exchange (H/DX) has been used to define the polypeptide backbone dynamics of full-length methyl CpG binding protein 2 (MeCP2) when free in solution and when bound to unmethylated and methylated DNA. Essentially the entire MeCP2 polypeptide chain underwent H/DX at rates faster than could be measured (i.e. complete exchange in ≤10 s), with the exception of the methyl DNA binding domain (MBD). Even the H/DX of the MBD was rapid compared with that of a typical globular protein. Thus, there is no single tertiary structure of MeCP2. Rather, the full-length protein rapidly samples many different conformations when free in solution. When MeCP2 binds to unmethylated DNA, H/DX is slowed several orders of magnitude throughout the MBD. Binding of MeCP2 to methylated DNA led to additional minor H/DX protection, and only locally within the N-terminal portion of the MBD. H/DX also was used to examine the structural dynamics of the isolated MBD carrying three frequent mutations associated with Rett syndrome. The effects of the mutations ranged from very little (R106W) to a substantial increase in conformational sampling (F155S). Our H/DX results have yielded fine resolution mapping of the structure of full-length MeCP2 in the absence and presence of DNA, provided a biochemical basis for understanding MeCP2 function in normal cells, and predicted potential approaches for the treatment of a subset of RTT cases caused by point mutations that destabilize the MBD