Quantitative assessment of near-infrared fluorescent proteins.

Recent progress in fluorescent protein development has generated a large diversity of near-infrared fluorescent proteins (NIR FPs), which are rapidly becoming popular probes for a variety of imaging applications. However, the diversity of NIR FPs poses a challenge for end-users in choosing the optimal one for a given application. Here we conducted a systematic and quantitative assessment of intracellular brightness, photostability, oligomeric state, chemical stability and cytotoxicity of 22 NIR FPs in cultured mammalian cells and primary mouse neurons and identified a set of top-performing FPs including emiRFP670, miRFP680, miRFP713 and miRFP720, which can cover a majority of imaging applications. The top-performing proteins were further validated for in vivo imaging of neurons in Caenorhabditis elegans, zebrafish, and mice as well as in mice liver. We also assessed the applicability of the selected NIR FPs for multicolor imaging of fusions, expansion microscopy and two-photon imaging.

Clinical characteristics and outcomes of children, adolescents and young adults with overweight or obesity and mental health disorders.

BACKGROUND: Mental disorders are important comorbidities in youth with obesity. Aim was to describe the clinical characteristics and outcome of youth with overweight or obesity having comorbid mental disorders. METHODS: Data from children, adolescents, and young adults (age 6-30 years) with overweight or obesity and mental disorders (depression, anxiety disorder, eating disorder, attention deficit disorder (ADHD)) from 226 centers in Germany and Austria participating in the Adiposity Patient Registry (APV) were analyzed and compared with those without reported mental disorders using regression modeling. RESULTS: Mental health comorbidity was reported in a total of 3969 out of 114,248 individuals with overweight or obesity: 42.5% had ADHD, 31.3% anxiety disorders, 24.3% depression, and 12.9% eating disorders. Being male (OR 1.39 (95%CI 1.27;1.52)), of older age (1.42 (1.25;1.62)), or with extreme obesity (1.45 (1.30;1.63)) were most strongly associated with mental health comorbidity. Regression analysis showed that mean BMI-SDS was significantly higher in the group of individuals with depression and eating disorders (BMI-SDS 2.13 (lower; upper mean:2.09;2.16) and 2.22 (2.17;2.26)) compared to those without reported mental health comorbidity (BMI-SDS 2.008 (2.005;2.011); p < 0.001). In youth with ADHD, BMI-SDS was lower compared to those without reported mental disorders (BMI-SDS 1.91 (1.89;1.93) vs 2.008 (2.005;2.011); p < 0.001). Proportion of severe obesity was higher in individuals with depression (23.7%), anxiety disorders (17.8%), and eating disorders (33.3%), but lower in ADHD (10.3%), compared to those without reported mental disorders (13.5%, p < 0.002). Proportions of dyslipidaemia and abnormal carbohydrate metabolism were not different in youth with and without reported mental health comorbidity. BMI-SDS change after one year of lifestyle intervention program ranged between -0.22 and -0.16 and was similar in youth without and with different mental disorders. CONCLUSION: Health care professionals caring for youth with overweight or obesity should be aware of comorbid mental disorders and regular mental health screening should be considered.

Sex inequalities in cardiovascular risk factors and their management in primary prevention in adults living with type 1 diabetes in Germany and France: findings from DPV and SFDT1.

INTRODUCTION & OBJECTIVES: To evaluate whether cardiovascular risk factors and their management differ in primary prevention between adult males and females with type 1 diabetes (T1D) in two European countries in 2020-2022 and sex inequalities in achievement of standards of care in diabetes. METHODS: We used 2020-2022 data of patients without a cardiovascular history in the Prospective Diabetes Follow-up registry (DPV) centres, in Germany, and the Société Francophone du Diabète- Cohorte Diabète de Type 1 cohort (SFDT1), in France. RESULTS: We included 2,657 participants from the DPV registry and 1,172 from the SFDT1 study. Body mass indexes were similar in females and males with similar proportions of HbA1c < 7% (DPV: 36.6 vs 33.0%, p = 0.06, respectively; SFDT1: 23.4 vs 25.7%, p = 0.41). Females were less overweight compared to men in DPV (55.4 vs 61.0%, p < 0.01) but not in SFDT1 (48.0 vs 44.9%, p = 0.33) and were less prone to smoke (DPV: 19.7 vs 25.8%, p < 0.01; SFDT1: 21.0 vs 26.0%, p = 0.07). Systolic blood pressure was lower in females than males with a higher rate of antihypertensive therapy in case of hypertension in females in DPV (70.5 vs 63.7%, p = 0.02) but not in SFDT1 (73.3 vs 68.6%, p = 0.64). In the case of microalbuminuria, ACEi-ARB were less often prescribed in women than men in DPV (21.4 vs 37.6%, p < 0.01) but not SFDT1 (73.3 vs 67.5.0%, p = 0.43). In females compared to males, HDL-cholesterol levels were higher; triglycerides were lower in both countries. In those with LDL-cholesterol > 3.4 mmol/L (DPV: 19.9 (females) vs 23.9% (males), p = 0.01; SFDT1 17.0 vs 19.2%, p = 0.43), statin therapy was less often prescribed in females than males in DPV (7.9 vs 17.0%, p < 0.01), SFDT1 (18.2 vs 21.0%, p = 0.42). CONCLUSION: In both studies, females in primary prevention have a better cardiovascular risk profile than males. We observed a high rate of therapeutic inertia, which might be higher in females for statin treatment and nephroprotection with ACEi-ARB, especially in Germany. Diabetologists should be aware of sex-specific differences in the management of cardiorenal risk factors to develop more personalized prevention strategies.

Continuous glucose monitoring in older adults with diabetes: Data from the diabetes prospective follow-up (DPV) registry.

AIMS: To analyse predictors for continuous glucose monitoring (CGM) use in people with diabetes aged ≥60 years using insulin therapy and to assess the rates of CGM use during recent years (2019-2021). RESEARCH DESIGN AND METHODS: Prospective study including 6849 individuals with diabetes and insulin therapy (type 2 diabetes: n = 5320; type 1 diabetes: n = 1529) aged ≥60 years. Data from 129 treatment centres were retrieved from the Diabetes Prospective Follow-up Registry (DPV) in March 2023. RESULTS: Sensor use in individuals aged ≥60 years has increased in type 1 (2019: 28%, 2020: 39%, 2021: 45%) and type 2 diabetes (2019: 10%, 2020: 16%, 2021: 18%). Predictors for sensor use in older individuals with type 1 diabetes are younger age and CSII use (p < 0.001). Predictors in older individuals with type 2 diabetes are younger age, longer diabetes duration, higher BMI and CSII use (p < 0.001). CONCLUSIONS: CGM has become more common in older adults with diabetes and will presumably increase further. Age is a predictor for sensor use in older adults with diabetes. Age-related physical barriers and insufficient usability of devices, lack of interest in technologies, but possibly also effects of prejudice on the grounds of age may contribute to this finding.

Time trends towards earlier puberty in boys and girls with type 1 diabetes: Insights from the German Diabetes Prospective Follow-up (DPV) registry, 2000 to 2021.

AIM: To examine the time trends and factors associated with the onset of puberty in children with type 1 diabetes (T1D) using data from the German Diabetes Prospective Follow-up (Diabetes-Patienten-Verlaufsdokumentation [DPV]) registry. METHODS: A total of 13 127 children with T1D, aged 6 to 18 years, were included in the analysis. Regression analysis was performed to investigate the relationship between diabetes duration, body mass index (BMI) standard deviation score (SDS), glycated haemoglobin (HbA1c) level, migration background, and the onset of puberty, stratified by sex. RESULTS: Our findings revealed a significant trend towards earlier puberty in both girls and boys with T1D over the observed period (2000 to 2021). Puberty onset in girls (thelarche Tanner stage B2) decreased from 11.48 (11.35-11.65) years in 2000 to 10.93 (10.79-11.08) years in 2021 and gonadarche (Tanner stage G2/testicular volume >3 mL) decreased from 12.62 (12.42-12.82) years in 2000 to 11.98 (11.79-12.16) years in 2021 in boys (both P < 0.001). Longer diabetes duration, higher BMI SDS, and lower HbA1c level were associated with earlier puberty in both sexes (P < 0.001). CONCLUSIONS: Our study highlights earlier puberty in children with T1D, influenced by BMI SDS, HbA1c level, and migration background. This has important implications for diabetes management and supporting healthy development. Further research is needed to understand the underlying mechanisms and develop potential interventions for this vulnerable population.

Poorly controlled pediatric type 1 diabetes mellitus is a risk factor for metabolic dysfunction associated steatotic liver disease (MASLD): An observational study.

OBJECTIVES: Recent studies have suggested a link between type 1 diabetes mellitus (T1D) and metabolic dysfunction associated steatotic liver disease (MASLD) in children and adolescent, but longitudinal evidence is lacking. This study aimed to investigate the potential association between poorly controlled T1D and elevated alanine aminotransferase (ALT), serving as a proxy for MASLD in children and adolescents over time. METHODS: The study included 32,325 children aged 2-17 years with T1D from Germany, Austria, and Switzerland who had undergone at least one assessment of liver enzyme levels recorded in the Diabetes-Patienten- Verlaufsdokumentation registry. Multivariable logistic and Cox regression models were calculated to show possible associations between T1D and elevated ALT values (>26 U/L in males, >22 U/L in females) as a proxy for MASLD. RESULTS: Children with poorly controlled T1D (HbA1c > 11%) exhibited increased odds of elevated ALT values, after adjustment for age, sex, diabetes duration and overweight (odds ratio [OR] 2.54; 95% confidence interval [CI], 2.10-3.10; p < 0.01). This finding is substantiated by a longitudinal analysis, which reveals that inadequately controlled T1D was associated with a higher hazard ratio (HR) of elevated ALT values compared to children with controlled T1D over an observation period extending up to 5.5 (HR: 1.54; 95% CI, 1.19-2.01; p < 0.01). CONCLUSION: In conclusion, the current study strongly links poorly controlled T1D in children and adolescents to MASLD irrespective of overweight. This association is not only present cross-sectionally but also increases over time. The study underscores the critical role of effective diabetes management in reducing the risk of MASLD in this population.

Development, circuitry, and function of the zebrafish cerebellum.

The cerebellum represents a brain compartment that first appeared in gnathostomes (jawed vertebrates). Besides the addition of cell numbers, its development, cytoarchitecture, circuitry, physiology, and function have been highly conserved throughout avian and mammalian species. While cerebellar research in avian and mammals is extensive, systematic investigations on this brain compartment in zebrafish as a teleostian model organism started only about two decades ago, but has provided considerable insight into cerebellar development, physiology, and function since then. Zebrafish are genetically tractable with nearly transparent small-sized embryos, in which cerebellar development occurs within a few days. Therefore, genetic investigations accompanied with non-invasive high-resolution in vivo time-lapse imaging represents a powerful combination for interrogating the behavior and function of cerebellar cells in their complex native environment.

BMI Z-Score (SDS) versus Calculated Body Fat Percentage: Association with Cardiometabolic Risk Factors in Obese Children and Adolescents.

INTRODUCTION: BMI or BMI-standardized deviation score (SDS) in children and adolescents is still the standard for weight classification. [BMJ. 2019;366:4293] developed a formula to calculate body fat percentage (%BF) based on age, sex, height, weight, and ethnicity. Using data from the German/Austrian APV registry, we investigated whether the calculated %BF is superior to BMI-SDS in predicting arterial hypertension, dyslipidaemia, and impaired glucose metabolism. METHODS: 94,586 children and adolescents were included (12.5 years, 48.3% male). Parental birth country (BC) was used to depict ethnicity (15.8% migration background); 95.67% were assigned to the ethnicity "white." %BF was calculated based on the Hudda formula. The relationship between BMI-SDS or %BF quartiles and outcome variables was investigated by logistic regression models, adjusted for age, sex, and migration background. Vuong test was applied to analyse predictive power. RESULTS: 58.4% had arterial hypertension, 33.5% had dyslipidaemia, and 11.6% had impaired glucose metabolism. Boys were significantly more often affected, although girls had higher calculated %BF (each p < 0.05). After adjustment, both models revealed significant differences between the quartiles (all p < 0.001). The predictive power of BMI-SDS was superior to %BF for all three comorbidities (all p < 0.05). DISCUSSION: The prediction of cardiometabolic comorbidities by calculated %BF was not superior to BMI-SDS. This formula developed in a British population may not be suitable for a central European population, which is applicable to this possibly less heterogeneous collective. Additional parameters, especially puberty status, should be taken into account. However, objective determinations such as bioimpedance analysis may possibly be superior to assess fat mass and cardiometabolic risk than calculated %BF.

Testing a model of benefit-finding and growth in youths with chronic health conditions.

BACKGROUND: The experience of benefit-finding and growth (BFG), defined as perceiving positive life changes resulting from adversity, is increasingly studied among youths with chronic health conditions (CCs). However, empirical evidence is scarce for explaining individual differences in BFG. The study aimed to test a model of BFG, including an interplay of personal and environmental factors and coping processes. METHODS: A sample of N = 498 youths (12-21 years) recruited from three German patient registries for CCs (type 1 diabetes: n = 388, juvenile idiopathic arthritis: n = 82, cystic fibrosis: n = 28) completed a questionnaire including self-reported optimism, social support from parents and peers, coping strategies, and BFG. The model was created to reflect the theoretical assumptions of the Life Crisis and Personal Growth model and current empirical evidence. Structural equation modeling was conducted to evaluate the incremental explanatory power of optimism, peer group integration, parental support, acceptance, cognitive reappraisal, and seeking social support over and above sociodemographic and disease-related characteristics. RESULTS: The model (CFI = 0.93; RMSEA = 0.04; SRMR = 0.05) explained 32% of the variance in BFG. Controlling for sociodemographic and disease-related characteristics, acceptance, cognitive reappraisal, and seeking social support were directly and positively linked to BFG. All tested coping strategies significantly mediated the association between optimism and BFG, whereas seeking social support significantly mediated the relation between peer group integration and BFG. DISCUSSION: The study stresses the prominent role of emotion-focused coping strategies and peer group integration in enhancing BFG in youths with CCs. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), no. DRKS00025125. Registered on May 17, 2021.

Motivational interviewing from the paediatricians' perspective: assessments after a 2-day training for physicians caring for adolescents with chronic medical conditions (CMCs).

BACKGROUND: Counselling adolescents with chronic medical conditions (CMCs) can be challenging regarding suitable interviewing skills and clinicians' attitudes toward the patient. Successful communication can be a key element of treatment. Motivational Interviewing (MI) is broadly applicable in managing behavioural problems and diseases by increasing patient motivation for lifestyle changes. However, data concerning the applicability, feasibility and implementation of MI sessions in everyday practice are missing from the physicians' point of view. METHOD: The present study was conducted as a mixed methods design. Twenty paediatricians were randomized to a 2-day MI course followed by MI consultations. Data were collected through a questionnaire one year after MI training. Factors for effective training and possible barriers to successful use of MI were examined. RESULTS: Completed questionnaires were returned by 19 of 20 paediatricians. The paediatricians' experiences with MI demonstrate that MI is regarded as a valuable tool when working with adolescents with CMCs. 95% of all respondents reported that they found MI education necessary for their clinical work and were using it also outside the COACH-MI study context. 73.7% percent saw potential to strengthen the connection to their patients by using MI. The doctors were already using more MI conversation techniques after a 2-day MI course. Obstacles were seen in the short training, the lack of time and missing undisturbed environment (interruptions by telephone, staff, etc.) during clinical flow. CONCLUSIONS: MI techniques are not yet a regular part of medical training. However, a 2-day MI course was rated effective and provided a lasting impact by physicians caring for children and adolescents with chronic medical conditions (CMCs), although booster sessions should be offered regularly. TRIAL REGISTRATION: The study was registered in the German Clinical Trials Register (DRKS00014043) on 26/04/2018.

Automated insulin delivery: benefits, challenges, and recommendations. A Consensus Report of the Joint Diabetes Technology Working Group of the European Association for the Study of Diabetes and the American Diabetes Association.

A technological solution for the management of diabetes in people who require intensive insulin therapy has been sought for decades. The last 10 years have seen substantial growth in devices that can be integrated into clinical care. Driven by the availability of reliable systems for continuous glucose monitoring, we have entered an era in which insulin delivery through insulin pumps can be modulated based on sensor glucose data. Over the past few years, regulatory approval of the first automated insulin delivery (AID) systems has been granted, and these systems have been adopted into clinical care. Additionally, a community of people living with type 1 diabetes has created its own systems using a do-it-yourself approach by using products commercialised for independent use. With several AID systems in development, some of which are anticipated to be granted regulatory approval in the near future, the joint Diabetes Technology Working Group of the European Association for the Study of Diabetes and the American Diabetes Association has created this consensus report. We provide a review of the current landscape of AID systems, with a particular focus on their safety. We conclude with a series of recommended targeted actions. This is the fourth in a series of reports issued by this working group. The working group was jointly commissioned by the executives of both organisations to write the first statement on insulin pumps, which was published in 2015. The original authoring group was comprised by three nominated members of the American Diabetes Association and three nominated members of the European Association for the Study of Diabetes. Additional authors have been added to the group to increase diversity and range of expertise. Each organisation has provided a similar internal review process for each manuscript prior to submission for editorial review by the two journals. Harmonisation of editorial and substantial modifications has occurred at both levels. The members of the group have selected the subject of each statement and submitted the selection to both organisations for confirmation.

The association between perinatal factors and cardiometabolic risk factors in children and adolescents with overweight or obesity: A retrospective two-cohort study.

BACKGROUND: Children with obesity have an increased risk of cardiometabolic risk factors, but not all children carry a similar risk. Perinatal factors, i.e., gestational age (GA) and birth weight for GA, may affect the risk for metabolic complications. However, there are conflicting data whether the association between birth size and cardiometabolic risk factors is independent among children with obesity. Moreover, differential effects of GA and birth weight for GA on cardiometabolic risk factors in pediatric obesity are still unexplored. We aimed to investigate the association between birth weight for GA and cardiometabolic risk factors in children and adolescents with overweight or obesity and to assess whether the association is modified by prematurity. METHODS AND FINDINGS: We conducted a retrospective study of 2 cohorts, using data from the world's 2 largest registers of pediatric obesity treatment-The Swedish childhood obesity treatment register (BORIS) and The Adiposity Patients Registry (APV) (1991 to 2020). Included were individuals with overweight or obesity between 2 to 18 years of age who had data of birth characteristics and cardiometabolic parameters. Birth data was collected as exposure variable and the first reported cardiometabolic parameters during pediatric obesity treatment as the main outcome. The median (Q1, Q3) age at the outcome measurement was 11.8 (9.4, 14.0) years. The main outcomes were hypertensive blood pressure (BP), impaired fasting glucose, elevated glycated hemoglobin (HbA1c), elevated total cholesterol, elevated low-density lipoprotein (LDL) cholesterol, elevated triglycerides, decreased high-density lipoprotein (HDL) cholesterol, and elevated transaminases. With logistic regression, we calculated the odds ratio (OR) and its 95% confidence interval (CI) for each cardiometabolic parameter. All the analyses were adjusted for sex, age, degree of obesity, migratory background, and register source. In total, 42,760 (51.9% females) individuals were included. Small for GA (SGA) was prevalent in 10.4%, appropriate for GA (AGA) in 72.4%, and large for GA (LGA) in 17.2%. Most individuals (92.5%) were born full-term, 7.5% were born preterm. Median (Q1, Q3) body mass index standard deviation score at follow-up was 2.74 (2.40, 3.11) units. Compared with AGA, children born SGA were more likely to have hypertensive BP (OR = 1.20 [95% CI 1.12 to 1.29], p < 0.001), elevated HbA1c (1.33 [1.06 to 1.66], p = 0.03), and elevated transaminases (1.21 [1.10 to 1.33], p < 0.001) as well as low HDL (1.19 [1.09 to 1.31], p < 0.001). On the contrary, individuals born LGA had lower odds for hypertensive BP (0.88 [0.83 to 0.94], p < 0.001), elevated HbA1c (0.81 [0.67 to 0.97], p < 0.001), and elevated transaminases (0.88 [0.81 to 0.94], p < 0.001). Preterm birth altered some of the associations between SGA and outcomes, e.g., by increasing the odds for hypertensive BP and by diminishing the odds for elevated transaminases. Potential selection bias due to occasionally missing data could not be excluded. CONCLUSIONS: Among children and adolescents with overweight/obesity, individuals born SGA are more likely to possess cardiometabolic risk factors compared to their counterparts born AGA. Targeted screening and treatment of obesity-related comorbidities should therefore be considered in this high-risk group of individuals.

An analysis of DPV and DIVE registry patients with chronic kidney disease according to the finerenone phase III clinical trial selection criteria.

BACKGROUND: The FIDELIO-DKD and FIGARO-DKD randomized clinical trials (RCTs) showed finerenone, a novel non-steroidal mineralocorticoid receptor antagonist (MRA), reduced the risk of renal and cardiovascular events in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Using RCT inclusion and exclusion criteria, we analyzed the RCT coverage for patients with T2DM and CKD in routine clinical practice in Germany. METHODS: German patients from the DPV/DIVE registries who were ≥ 18 years, had T2DM and CKD (an estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 OR eGFR ≥ 60 mL/min/1.73m2 and albuminuria [≥ 30 mg/g]) were included. RCT inclusion and exclusion criteria were then applied, and the characteristics of the two populations compared. RESULTS: Overall, 65,168 patients with T2DM and CKD were identified from DPV/DIVE. Key findings were (1) Registry patients with CKD were older, less often male, and had a lower eGFR, but more were normoalbuminuric vs the RCTs. Cardiovascular disease burden was higher in the RCTs; diabetic neuropathy, lipid metabolism disorders, and peripheral arterial disease were more frequent in the registry. CKD-specific drugs (e.g., angiotensin-converting enzyme inhibitors [ACEi] and angiotensin receptor blocker [ARBs]) were used less often in clinical practice; (2) Due to the RCT's albuminuric G1/2 to G4 CKD focus, they did not cover 28,147 (43.2%) normoalbuminuric registry patients, 4,519 (6.9%) albuminuric patients with eGFR < 25, and 6,565 (10.1%) patients with microalbuminuria but normal GFR (≥ 90 ml/min); 3) As RCTs required baseline ACEi or ARB treatment, the number of comparable registry patients was reduced to 28,359. Of these, only 12,322 (43.5%) registry patients fulfilled all trial inclusion and exclusion criteria. Registry patients that would have been eligible for the RCTs were more often male, had higher eGFR values, higher rates of albuminuria, more received metformin, and more SGLT-2 inhibitors than patients that would not be eligible. CONCLUSIONS: Certain patient subgroups, especially non-albuminuric CKD-patients, were not included in the RCTs. Although recommended by guidelines, there was an undertreatment of CKD-patients with renin-angiotensin system (RAS) blockers. Further research into patients with normoalbuminuric CKD and a wider prescription of RAS blocking agents for CKD patients in clinical practice appears warranted.

Empagliflozin is associated with lower cardiovascular risk compared with dipeptidyl peptidase-4 inhibitors in adults with and without cardiovascular disease: EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study results from Europe and Asia.

BACKGROUND: Studies that have reported lower risk for cardiovascular outcomes in users of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) are limited by residual cofounding and lack of information on prior cardiovascular disease (CVD). This study compared risk of cardiovascular events in patients within routine care settings in Europe and Asia with type 2 diabetes (T2D) initiating empagliflozin compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) stratified by pre-existing CVD and history of heart failure (HF). METHODS AND RESULTS: Adults initiating empagliflozin and DPP-4i in 2014-2018/19 from 11 countries in Europe and Asia were compared using propensity score matching and Cox proportional hazards regression to assess differences in rates of primary outcomes: hospitalisation for heart failure (HHF), myocardial infarction (MI), stroke; and secondary outcomes: cardiovascular mortality (CVM), coronary revascularisation procedure, composite outcome including HHF or CVM, and 3-point major adverse cardiovascular events (MACE: MI, stroke and CVM). Country-specific results were meta-analysed and pooled hazard ratios (HR) with 95% confidence intervals (CI) from random-effects models are presented. In total, 85,244 empagliflozin/DPP4i PS-matched patient pairs were included with overall mean follow-up of 0.7 years. Among those with pre-existing CVD, lower risk was observed for HHF (HR 0.74; 95% CI 0.64-0.86), CVM (HR 0.55; 95% CI 0.38-0.80), HHF or CVM (HR 0.57; 95% CI 0.48-0.67) and stroke (HR 0.79; 95% CI 0.67-0.94) in patients initiating empagliflozin vs DPP-4i. Similar patterns were observed among patients without pre-existing CVD and those with and without pre-existing HF. CONCLUSION: These results from diverse patient populations in routine care settings across Europe and Asia demonstrate that initiation of empagliflozin compared to DPP-4i results in favourable cardioprotective effects regardless of pre-existing CVD or HF status.

Low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol in type 1 diabetes and type 2 diabetes: Lipid goal attainment in a large German-Austrian diabetes registry.

AIM: To assess the implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline recommendations for lipid-lowering therapies among more than 30 000 patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) in a German and Austrian registry from 2020 to 2022. MATERIALS AND METHODS: Registry data from 2020 and 2021 of 32 170 adult patients (8314 patients with T1D and 23 856 with T2D) were stratified according to the 2019 ESC/EAS risk categories, and guideline-based low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) goal attainment was analysed. RESULTS: In patients with T1D (median age 38.35 [20.51-57.13] years), overall statin use was 19.3%, ezetimibe use was 2.2% and the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors or fibrates was less than 1%. In patients with T2D (median age 68.76 [58.86-78.39] years), 45.7% received statins, 3.4% received ezetimibe, and fibrates and PCSK9 inhibitors were used by 1% and 0.1%, respectively. Among patients with T1D, 6.16% reached their risk-based recommended LDL-C goal of less than 55 mg/dL (very high risk), 10.97% of less than 70 mg/dL (high risk), and 69.50% of less than 100 mg/dL (moderate risk), respectively. In patients with T2D, 11.81% reached their risk-based goal of LDL-C less than 55 mg/dL, 16.25% of less than 70 mg/dL, and 51.33% of less than 100 mg/dL. Non-HDL-C goals were reached more often, with 15.3%, 25.52% and 91.61% in patients with T1D and 18.56%, 17.96% and 82.30% in patients with T2D for very high, high and moderate risk, respectively. CONCLUSION: Approximately 2 years after publication of the guidelines, LDL-C and non-HDL-C goal attainment was rarely achieved in patients with T1D and T2D with a high or very high cardiovascular risk.

Validation of a risk prediction model for early chronic kidney disease in patients with type 2 diabetes: Data from the German/Austrian Diabetes Prospective Follow-up registry.

AIM: To validate a recently proposed risk prediction model for chronic kidney disease (CKD) in type 2 diabetes (T2D). MATERIALS AND METHODS: Subjects from the German/Austrian Diabetes Prospective Follow-up (DPV) registry with T2D, normoalbuminuria, an estimated glomerular filtration rate of 60 ml/min/1.73m2 or higher and aged 39-75 years were included. Prognostic factors included age, body mass index (BMI), smoking status and HbA1c. Subjects were categorized into low, moderate, high and very high-risk groups. Outcome was CKD occurrence. RESULTS: Subjects (n = 10 922) had a mean age of 61 years, diabetes duration of 6 years, BMI of 31.7 kg/m2 , HbA1c of 6.9% (52 mmol/mol); 9.1% had diabetic retinopathy and 16.3% were smokers. After the follow-up (~59 months), 37.4% subjects developed CKD. The area under the curve (AUC; unadjusted base model) was 0.58 (95% CI 0.57-0.59). After adjustment for diabetes and follow-up duration, the AUC was 0.69 (95% CI 0.68-0.70), indicating improved discrimination. After follow-up, 15.0%, 20.1%, 27.7% and 40.2% patients in the low, moderate, high and very high-risk groups, respectively, had developed CKD. Increasing risk score correlated with increasing cumulative risk of incident CKD over a median of 4.5 years of follow-up (P < .0001). CONCLUSIONS: The predictive model achieved moderate discrimination but good calibration in a German/Austrian T2D population, suggesting that the model may be relevant for determining CKD risk.

A prospective analysis of the long-term impact of the COVID-19 pandemic on well-being and health care among children with a chronic condition and their families: a study protocol of the KICK-COVID study.

BACKGROUND: There is consistent evidence that the COVID-19 pandemic is associated with an increased psychosocial burden on children and adolescents and their parents. Relatively little is known about its particular impact on high-risk groups with chronic physical health conditions (CCs). Therefore, the primary aim of the study is to analyze the multiple impacts on health care and psychosocial well-being on these children and adolescents and their parents. METHODS: We will implement a two-stage approach. In the first step, parents and their underage children from three German patient registries for diabetes, obesity, and rheumatic diseases, are invited to fill out short questionnaires including questions about corona-specific stressors, the health care situation, and psychosocial well-being. In the next step, a more comprehensive, in-depth online survey is carried out in a smaller subsample. DISCUSSION: The study will provide insights into the multiple longer-term stressors during the COVID-19 pandemic in families with a child with a CC. The simultaneous consideration of medical and psycho-social endpoints will help to gain a deeper understanding of the complex interactions affecting family functioning, psychological well-being, and health care delivery. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), no. DRKS00027974. Registered on 27th of January 2022.

Functionally distinct Purkinje cell types show temporal precision in encoding locomotion.

Purkinje cells, the principal neurons of cerebellar computations, are believed to comprise a uniform neuronal population of cells, each with similar functional properties. Here, we show an undiscovered heterogeneity of adult zebrafish Purkinje cells, revealing the existence of anatomically and functionally distinct cell types. Dual patch-clamp recordings showed that the cerebellar circuit contains all Purkinje cell types that cross-communicate extensively using chemical and electrical synapses. Further activation of spinal central pattern generators (CPGs) revealed unique phase-locked activity from each Purkinje cell type during the locomotor cycle. Thus, we show intricately organized Purkinje cell networks in the adult zebrafish cerebellum that encode the locomotion rhythm differentially, and we suggest that these organizational properties may also apply to other cerebellar functions.

A stopping criterion for iterative proton CT image reconstruction based on correlated noise properties.

BACKGROUND: Whereas filtered back projection algorithms for voxel-based CT image reconstruction have noise properties defined by the filter, iterative algorithms must stop at some point in their convergence and do not necessarily produce consistent noise properties for images with different degrees of heterogeneity. PURPOSE: A least-squares iterative algorithm for proton CT (pCT) image reconstruction converges toward a unique solution for relative stopping power (RSP) that optimally fits the protons. We present a stopping criterion that delivers solutions with the property that correlations of RSP noise between voxels are relatively low. This provides a method to produce pCT images with consistent noise properties useful for proton therapy treatment planning, which relies on summing RSP along lines of voxels. Consistent noise properties will also be useful for future studies of image quality using metrics such as contrast to noise ratio, and to compare RSP noise and dose of pCT with other modalities such as dual-energy CT. METHODS: With simulated and real images with varying heterogeneity from a prototype clinical proton imaging system, we calculate average RSP correlations between voxel pairs in uniform regions-of-interest versus distance between voxels. We define a parameter r, the remaining distance to the unique solution relative to estimated RSP noise, and our stopping criterion is based on r falling below a chosen value. RESULTS: We find large correlations between voxels for larger values of r, and anticorrelations for smaller values. For r in the range of 0.5-1, voxels are relatively uncorrelated, and compared to smaller values of r have lower noise with only slight loss of spatial resolution. CONCLUSIONS: Iterative algorithms not using a specific metric or rationale for stopping iterations may produce images with an unknown and arbitrary level of convergence or smoothing. We resolve this issue by stopping iterations of a least-squares iterative algorithm when r reaches the range of 0.5-1. This defines a pCT image reconstruction method with consistent statistical properties optimal for clinical use, including for treatment planning with pCT images.

WE3DS: An RGB-D Image Dataset for Semantic Segmentation in Agriculture.

Smart farming (SF) applications rely on robust and accurate computer vision systems. An important computer vision task in agriculture is semantic segmentation, which aims to classify each pixel of an image and can be used for selective weed removal. State-of-the-art implementations use convolutional neural networks (CNN) that are trained on large image datasets. In agriculture, publicly available RGB image datasets are scarce and often lack detailed ground-truth information. In contrast to agriculture, other research areas feature RGB-D datasets that combine color (RGB) with additional distance (D) information. Such results show that including distance as an additional modality can improve model performance further. Therefore, we introduce WE3DS as the first RGB-D image dataset for multi-class plant species semantic segmentation in crop farming. It contains 2568 RGB-D images (color image and distance map) and corresponding hand-annotated ground-truth masks. Images were taken under natural light conditions using an RGB-D sensor consisting of two RGB cameras in a stereo setup. Further, we provide a benchmark for RGB-D semantic segmentation on the WE3DS dataset and compare it with a solely RGB-based model. Our trained models achieve up to 70.7% mean Intersection over Union (mIoU) for discriminating between soil, seven crop species, and ten weed species. Finally, our work confirms the finding that additional distance information improves segmentation quality.