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Abstract Under the EU’s new “Farm to Fork” strategy, crop production systems should rapidly become more environmentally friendly. In particular, by adopting agroecological measures that support functional biodiversity and improve ecosystem services for crop production, this paper contributes to the ongoing efforts in characterizing the socio-economic effects that the upscaling of these measures entails, by looking into two key measures: flower strips and mulching. One important socio-economic aspect of their adoption is their potential impact on agricultural income; however, knowledge on costs and benefits of measures enhancing functional biodiversity at the farm level is still limited. In order to improve these shortcomings our approach makes use of data from field experiments completed with interviews to provide cost–benefit results for flower strips and organic mulching. The estimations show that for “flower strips,” on average costs could be covered by compensation payments. Regarding the in-crop measure “organic mulching,” the benefits potentially outweigh the costs under the frame conditions of organic agriculture. The analysis also highlights some obstacles and knowledge gaps in the estimation of benefits, especially for off-crop measures like flower strips.

Experimental studies in animal models of aging such as nematodes, fruit flies or mice have observed that decreased levels of insulin or insulin signaling promotes longevity. In humans, hyperinsulinemia and concomitant insulin resistance are associated with an elevated risk of age-related diseases suggestive of a shortened healthspan. Age-related disorders include neurodegenerative diseases, hypertension, cardiovascular disease, and type 2 diabetes. High ambient insulin concentrations promote increased lipogenesis and fat storage, heightened protein synthesis and accumulation of non-functional polypeptides due to limited turnover capacity. Moreover, there is impaired autophagy activity, and less endothelial NO synthase activity. These changes are associated with mitochondrial dysfunction and oxidative stress. The cellular stress induced by anabolic activity of insulin initiates an adaptive response aiming at maintaining homeostasis, characterized by activation of the transcription factor Nrf2, of AMP activated kinase, and an unfolded protein response. This protective response is more potent in the long-lived human species than in short-lived models of aging research resulting in a stronger pro-aging impact of insulin in nematodes and fruit flies. In humans, resistance to insulin-induced cell stress decreases with age, because of an increase of insulin and insulin resistance levels but less Nrf2 activation. These detrimental changes might be contained by adopting a lifestyle that promotes low insulin/insulin resistance levels and enhances an adaptive response to cellular stress, as observed with dietary restriction or exercise.

Abstract Background This study was to compare the outcomes of 360° intra-operative laser retinopexy (ILR) and focal laser retinopexy in treating patients with pars plans vitrectomy (PPV) for primary rhegmatogenous retinal detachment (RRD). To identify other potential risk factors for retinal re-detachment after primary PPV. Methods This was a retrospective cohort study. Three hundred and forty-four consecutive cases of primary rhegmatogenous retinal detachment treated with PPV were included between July 2013 and July 2018. Clinical characteristics and surgical outcomes were compared between focal laser retinopexy and additional 360° intra-operative laser retinopexy groups. Both univariate and multiple variable analysis were used to identify potential risk factors for retinal re-detachment. Results Median follow-up was 6.2 months (Q1, Q3:2.0, 17.2). As estimated with survival analysis, the 360º ILR group had the incidence of 9.74% and focal laser 19.54% at 6 months postoperatively. At 12 months postoperatively the difference was 10.78% vs. 25.21%. The difference in survival rates was significant (p = 0.0021). In multivariate Cox regression, the risk factors for retinal re-detachment were without additional 360° ILR, diabetes and macula off before the primary surgery (relatively OR = 0.456, 95%-CI [0.245–0.848], p

BackgroundDespite effective treatment options, chronic kidney disease (CKD) has become a major cause of mortality worldwide due to the ever-increasing number of patients with type 2 diabetes mellitus (T2DM). Guideline-compliant, at least, annual screening of patients with T2DM is crucial to prevent renal disease progression. However, data on the prevalence of CKD in patients with T2DM and on screening frequency are limited. SMART-Finder is the first study to exclusively use data provided directly by patients via an adherence app to collect information on the prevalence of CKD, risk factors, disease management, and quality of life of patients with T2DM in Germany. ObjectiveThe primary objective of this study is to determine the proportion of patients with T2DM and an elevated urine albumin-to-creatinine ratio (UACR; albumin-to-creatinine ratio stage A2 and A3) at baseline and after 12 (±3) months. Secondary objectives include the proportion of patients who remain in or switch to another albumin-to-creatinine ratio classification category after 12 months, information on quality of life, disease awareness, and adherence rates, as well as the proportion of patients without any UACR-screening data. Recruitment occurs via push notification among MyTherapy app users with T2DM. MethodsThis is a single-arm, retrospective/prospective, observational, digital, patient-centered cohort study, with recruitment and data documentation via a health app. Required routine laboratory data are provided by treating physicians to their patients for data entry. The study population includes adult patients with T2DM documenting their data in the MyTherapy app using their own smartphone or tablet. Study participants are provided with a specifically developed electronic case report form containing questions on demographic and general data, quality of life, disease awareness, and laboratory values including estimated glomerular filtration rate, UACR, hemoglobin 1Ac, and blood pressure. Apart from demographic and general data, all data are collected at baseline and 12 months after the last UACR assessment. An automatically generated push notification reminds participants of the second data entry. The extracted and pseudonymized data are analyzed descriptively. ResultsThe enrollment period for this study started in February 2023 and shall end after 12 months or after the enrollment of 5000 patients. An interim analysis is planned 3 months after the inclusion of the first patient and the final analysis after 12 months of follow-up. ConclusionsOverall, the study will contribute to minimizing the existing data gap on the prevalence of CKD in patients with T2DM in Germany, provide important insights into the current disease management of patients with T2DM in everyday clinical practice in Germany, and support guideline-based care for the participating patients. International Registered Report Identifier (IRRID)PRR1-10.2196/44996

Abstract During starvation, fasting, or a diet containing little digestible carbohydrates, the circulating insulin levels are decreased. This promotes lipolysis, and the breakdown of fat becomes the major source of energy. The hepatic energy metabolism is regulated so that under these circumstances, ketone bodies are generated from β-oxidation of fatty acids and secreted as ancillary fuel, in addition to gluconeogenesis. Increased plasma levels of ketone bodies thus indicate a dietary shortage of carbohydrates. Ketone bodies not only serve as fuel but also promote resistance to oxidative and inflammatory stress, and there is a decrease in anabolic insulin-dependent energy expenditure. It has been suggested that the beneficial non-metabolic actions of ketone bodies on organ functions are mediated by them acting as a ligand to specific cellular targets. We propose here a major role of a different pathway initiated by the induction of oxidative stress in the mitochondria during increased ketolysis. Oxidative stress induced by ketone body metabolism is beneficial in the long term because it initiates an adaptive (hormetic) response characterized by the activation of the master regulators of cell-protective mechanism, nuclear factor erythroid 2-related factor 2 (Nrf2), sirtuins, and AMP-activated kinase. This results in resolving oxidative stress, by the upregulation of anti-oxidative and anti-inflammatory activities, improved mitochondrial function and growth, DNA repair, and autophagy. In the heart, the adaptive response to enhanced ketolysis improves resistance to damage after ischemic insults or to cardiotoxic actions of doxorubicin. Sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors may also exert their cardioprotective action via increasing ketone body levels and ketolysis. We conclude that the increased synthesis and use of ketone bodies as ancillary fuel during periods of deficient food supply and low insulin levels causes oxidative stress in the mitochondria and that the latter initiates a protective (hormetic) response which allows cells to cope with increased oxidative stress and lower energy availability. Keywords Ketogenic diet, Ketone bodies, Beta hydroxybutyrate, Insulin, Obesity, Type 2 diabetes, Inflammation, Oxidative stress, Cardiovascular disease, SGLT2, Hormesis

BackgroundThe use of digital technology to assess patients remotely can reduce clinical study costs. In the European Union, the 2D matrix code on prescription drug packaging serves as a unique identifier of a given package of medication, and thus, also of the patient receiving that medication. Scanning of the 2D matrix code may therefore allow remote patient authentication in clinical studies. ObjectiveThe aim of the DePRO study was to assess the feasibility of a fully digital data-capture workflow, the authentication of participants via drug packaging 2D matrix codes, in patients with type 2 diabetes mellitus (T2DM) who use metformin. The primary objective was to describe the self-care activities of these patients. Secondary objectives were to evaluate (1) the self-reported health status of these patients, (2) the association of self-care activities with demographics and disease characteristics, and (3) the usability of the my ePRO app. MethodsDePRO was an observational, multicenter, cross-sectional, digital, and patient-driven study conducted in Germany from June to December 2020. Adult patients prescribed metformin were invited to participate via their pharmacist or a medication tracker app. Participants downloaded the my ePRO app onto their own mobile device, scanned the 2D matrix code on their metformin package for registration and authentication, and provided informed consent via an electronic form. They were then able to complete a study-specific questionnaire on demographics and clinical characteristics, the German version of the Summary of Diabetes Self-Care Activities measure (SDSCA-G), the Diabetes Treatment Satisfaction Questionnaire (DTSQ), and the EQ-5D-5L. The patients conducted the study without support from a health care professional. Statistical analyses were exploratory and descriptive. ResultsIn total, 3219 patients were invited to participate. The proportion of patients giving consent was greater among those invited by pharmacists (19/217, 8.8%) than among those invited via the medication tracker app (13/3002, 0.4%). Of the 29 patients eligible for analysis, 28 (97%) completed all study questionnaires. Most of the patients (23/29, 79%) were aged

Abstract Background Insulin shares a limited physiological concentration range with other endocrine hormones. Not only too low, but also too high systemic insulin levels are detrimental for body functions. Main body The physiological function and clinical relevance of insulin are usually seen in association with its role in maintaining glucose homeostasis. However, insulin is an anabolic hormone which stimulates a large number of cellular responses. Not only too low, but also excess insulin concentrations are detrimental to the physiological balance. Although the glucoregulatory activity of insulin is mitigated during hyperinsulinemia by dampening the efficiency of insulin signaling (“insulin resistance”), this is not the case for most other hormonal actions of insulin, including the promotion of protein synthesis, de novo lipogenesis, and cell proliferation; the inhibition of lipolysis, of autophagy-dependent cellular turnover, and of nuclear factor E2-related factor-2 (Nrf2)-dependent antioxidative; and other defense mechanisms. Hence, there is no general insulin resistance but selective impairment of insulin signaling which causes less glucose uptake from the blood and reduced activation of endothelial NO synthase (eNOS). Because of the largely unrestricted insulin signaling, hyperinsulinemia increases the risk of obesity, type 2 diabetes, and cardiovascular disease and decreases health span and life expectancy. In epidemiological studies, high-dose insulin therapy is associated with an increased risk of cardiovascular disease. Randomized controlled trials of insulin treatment did not observe any effect on disease risk, but these trials only studied low insulin doses up to 40 IU/day. Proof for a causal link between elevated insulin levels and cardiovascular disease risk comes from Mendelian randomization studies comparing individuals with genetically controlled low or high insulin production. Conclusions The detrimental actions of prolonged high insulin concentrations, seen also in cell culture, argue in favor of a lifestyle that limits circadian insulin levels. The health risks associated with hyperinsulinemia may have implications for treatment regimens used in type 2 diabetes.

In conservation agriculture, conservation tillage potentially influences the physical, chemical, and biological quality of the soil. Although the effects of conservation agriculture on the soil’s physical properties have been studied in conventional management systems, studies on organic farming systems, especially concerning long-term changes, are scarce. This study summarizes the results of physical and mechanical soil parameters obtained over the initial 10 years of different conservation management treatments (plowing versus reduced tillage with and without compost application) in an organic field trial conducted in central Germany. Moreover, as a research objective, the effects of soil conservation measures on soil’s physical quality were evaluated. Differences in the soil’s physical quality during treatments were mainly detected in the topsoil. At a depth of 0.10–0.24 m, the total porosity and air capacity were lower, and the bulk density was higher in the reduced-tillage systems, compared to those of the plowed treatments. Additionally, the soil’s mechanical stability (precompression stress) was higher at a depth of 0.10 m for reduced-tillage systems combined with compost application. In addition, the soil’s aggregate stability was enhanced in the reduced-tillage systems (higher mean weight diameter, as determined via wet sieving). Overall, the reduced-tillage treatments did not exceed the critical physical values of the soil, nor affect the functionality of the soil (saturated hydraulic conductivity), thereby demonstrating its feasibility as a sustainable technique for organic farming. Future studies should include measures to ameliorate compaction zones in reduced-tillage treatments, e.g., by applying subsoiling techniques in combination with deep-rooting crops to prevent limited rooting space resulting from the high mechanical impedance, especially under dry soil conditions.

Background: Recently published genetic studies have indicated a causal link between elevated insulin levels and cardiovascular disease (CVD) risk. We, therefore, hypothesized that increased fasting insulin levels are also associated with precursors of CVD such as endothelial lesions.Methods: Middle-aged (≥40 years, n = 1,639) employees were followed up for the occurrence of increased intima media thickness (IMT ≥ 1 mm) or plaques in abdominal or cervical arteries (arteriosclerosis). Multivariable logistic regression analyses determined the incidence of increased IMT or arteriosclerosis. Adjusted relative risk (ARR) for increased IMT and arteriosclerosis was calculated by using Mantel-Haenszel analysis.Results: Increased IMT was diagnosed in 238 participants (15 %) and 328 (20 %) developed arteriosclerosis after 5 years of follow-up. Logistic regression analysis identified fasting insulin, BMI and smoking as risk factors for both cardiovascular endpoints (all p < 0.05), whereas age and diastolic blood pressure were risk factors for increased IMT only, and male sex was associated with incident arteriosclerosis only (all p < 0.01). Additional adjustment for BMI change during follow-up did not modify these associations (including fasting insulin), but adjustment for fasting insulin change during follow-up removed BMI as risk factor for both cardiovascular endpoints. Fasting insulin change during follow-up but not BMI change associated with increased IMT and arteriosclerosis (both p < 0.001). ARR analysis indicated that high fasting insulin and BMI added to age and sex as risk factors. Homeostatic model assessment of insulin resistance (HOMA-IR) did not associate with either cardiovascular endpoint in any model and smoking did not increase the risk conferred by high fasting insulin levels.Conclusions: Higher fasting insulin levels and increases in fasting insulin over time are associated with atherogenic progression and supersede BMI as well as HOMA-IR as risk factors.

The Colorado potato beetle (CPB) is an exceptionally challenging potato pest. Some regenerative farmers have reported that the use of transferred green manure mulch can considerably reduce CBP damage. Previous studies confirm this observation, but mainly with straw mulch, which is rarely used in Central Europe, and not embedded in the new regenerative cropping approach. For this, six trials conducted between 2014 and 2019 were evaluated, comparing CPB infestation in potatoes with and without transferred mulch as well as under a plough as a minimum till regime. In three out of six experiments, compost application was an additional factor. (I) Over all experiments, mulch significantly reduced initial infestation (−24%), egg masses (−27%) and larvae (−75%). Compost and reduced tillage added to these effects; (II) Mulch mainly resulted in delayed CPB infestation; (III) In a particularly warm season, when a second generation of CPB managed to emerge, regulatory effects of the mulch were not sufficient; (IV) Combination of transferred nutrient rich green manure mulch with reduced tillage, compost and other regenerative or agro-ecological techniques is recommended to achieve maximum regulation of CPB.

Abstract Background Hospital antimicrobial stewardship programs (ASPs) aim to promote judicious use of antimicrobials to combat antimicrobial resistance. For ASPs to be developed, adopted, and implemented, an economic value assessment is essential. Few studies demonstrate the cost-effectiveness of ASPs. This systematic review aimed to evaluate the economic and clinical impact of ASPs. Methods An update to the Dik et al. systematic review (2000–2014) was conducted on EMBASE and Medline using PRISMA guidelines. The updated search was limited to primary research studies in English (30 September 2014–31 December 2017) that evaluated patient and/or economic outcomes after implementation of hospital ASPs including length of stay (LOS), antimicrobial use, and total (including operational and implementation) costs. Results One hundred forty-six studies meeting inclusion criteria were included. The majority of these studies were conducted within the last 5 years in North America (49%), Europe (25%), and Asia (14%), with few studies conducted in Africa (3%), South America (3%), and Australia (3%). Most studies were conducted in hospitals with 500–1000 beds and evaluated LOS and change in antibiotic expenditure, the majority of which showed a decrease in LOS (85%) and antibiotic expenditure (92%). The mean cost-savings varied by hospital size and region after implementation of ASPs. Average cost savings in US studies were $732 per patient (range: $2.50 to $2640), with similar trends exhibited in European studies. The key driver of cost savings was from reduction in LOS. Savings were higher among hospitals with comprehensive ASPs which included therapy review and antibiotic restrictions. Conclusions Our data indicates that hospital ASPs have significant value with beneficial clinical and economic impacts. More robust published data is required in terms of implementation, LOS, and overall costs so that decision-makers can make a stronger case for investing in ASPs, considering competing priorities. Such data on ASPs in lower- and middle-income countries is limited and requires urgent attention.

Objective Early diagnosis of atrial fibrillation (AFib) is a priority for stroke prevention. We sought to test four commercial pulse detection systems (CPDSs) for ability to distinguish AFib from normal sinus rhythm using a published algorithm (Zhou et al., PLoS One 2015;10:e0136544), compared with visual diagnosis by electrocardiogram inspection. Methods BAYathlon was a prospective, non-interventional, single-centre study. Adult cardiology patients with documented AFib or sinus rhythm who were due to have a routine 5-min electrocardiogram were randomized to undergo a parallel 5-min pulse assessment with a Polar V800, eMotion Faros 360, TomTom heart rate monitor, or Adidas miCoach Smart Run. Results 144 patients (73 with AFib, 71 with sinus rhythm (based on electrocardiograms); median age: 73 years; 53.5% male) were analysed. Algorithm sensitivities (primary endpoint) and specificities for AFib when applied to CPDS recordings were 93.3% and 94.1% with the Polar V800, 90.0% and 84.2% with the eMotion Faros 360, and 0% and 100% with the other CPDSs (analysis period: 127 heart rate signals + 2 min). When applied to routine electrocardiograms, the algorithm correctly detected AFib in 71/73 patients. Different analysis periods (127 heart rate signals +1 or 3 min) only slightly changed the sensitivities with the Polar V800 and eMotion Faros 360 and had no effect on the sensitivities with the other CPDSs. Conclusion AFib screening using the applied algorithm is feasible with the Polar V800 and eMotion Faros 360 (which provide RR interval data) but not with the other CPDSs (which provide pre-processed heart rate time series). ClinicalTrials.gov identifier: NCT02875106

Abstract Lifestyle factors conferring increased diabetes risk are associated with elevated basal insulin levels (hyperinsulinaemia). The latter predicts later obesity in children and adolescents. A causal role of hyperinsulinaemia for adipose tissue growth is probable because pharmacological reduction of insulin secretion lowers body weight in people who are obese. Genetic inactivation of insulin gene alleles in mice also lowers their systemic insulin levels and prevents or ameliorates high-fat diet-induced obesity. Hyperinsulinaemia causes weight gain because of a physiological property of insulin. Insulin levels that are on the high side of normal, or which are slightly elevated, are sufficient to suppress lipolysis and promote lipogenesis in adipocytes. The effect of insulin on glucose transport or hepatic glucose production requires six or two times higher hormone levels, respectively. It seems justified to suggest a lifestyle that avoids high insulin levels in order to limit anabolic fat tissue activity.

Abstract Background Environmental and lifestyle changes, in addition to the ageing of populations, are generally believed to account for the rapid global increase in type 2 diabetes prevalence and incidence in recent decades. Discussion In this review, we present a comprehensive overview of factors contributing to diabetes risk, including aspects of diet quality and quantity, little physical activity, increased monitor viewing time or sitting in general, exposure to noise or fine dust, short or disturbed sleep, smoking, stress and depression, and a low socioeconomic status. In general, these factors promote an increase in body mass index. Since loss of β-cell function is the ultimate cause of developing overt type 2 diabetes, environmental and lifestyle changes must have resulted in a higher risk of β-cell damage in those at genetic risk. Multiple mechanistic pathways may come into play. Conclusions Strategies of diabetes prevention should aim at promoting a ‘diabetes-protective lifestyle’ whilst simultaneously enhancing the resistance of the human organism to pro-diabetic environmental and lifestyle factors. More research on diabetes-protective mechanisms seems warranted.

ObjectiveAs a result of unhealthy lifestyles, reduced numbers of healthcare providers are having to deal with an increasing number of diabetes patients. In light of this shortage of physicians and nursing staff, new concepts of care are needed. The aim of this scoping review is to review the literature and examine the effects of task delegation to non-physician health professionals, with a further emphasis on inter-professional care.Research design and methodsSystematic searches were performed using the PubMed, Embase and Google Scholar databases to retrieve papers published between January 1994 and December 2017. Randomised/non-randomised controlled trials and studies with a before/after design that described the delegation of tasks from physicians to non-physicians in diabetes care were included in the search. This review is a subgroup analysis that further assesses all the studies conducted using a team-based approach.ResultsA total of 45 studies with 12,092 patients met the inclusion criteria. Most of the interventions were performed in an outpatient setting with type-2 diabetes mellitus patients. The non-physician healthcare professionals involved in the team were nurses, pharmacists, community health workers and dietitians. Most studies showed significant improvements in glycaemic control and high patient satisfaction, while there were no indications that the task delegation affected quality of life scores.ConclusionsThe findings of the review suggest that task delegation can provide equivalent glycaemic control and potentially lead to an improvement in the quality of care. However, this review revealed a lack of clinical endpoints, as well as an inconsistency between the biochemical outcome parameters and the patient-centred outcome parameters. Given the vast differences between the individual healthcare systems used around the world, further high-quality research with an emphasis on long-term outcome effects and the expertise of non-physicians is needed.

On March 25th 2019, the Belle II detector recorded the first collisions delivered by the SuperKEKB accelerator. This marked the beginning of the physics run with vertex detector. The vertex detector was aligned initially with cosmic ray tracks without magnetic field simultaneously with the drift chamber. The alignment method is based on Millepede II and the General Broken Lines track model and includes also the muon system or primary vertex position alignment. To control weak modes, we employ sensitive validation tools and various track samples can be used as alignment input, from straight cosmic tracks to mass-constrained decays. With increasing luminosity and experience, the alignment is approaching the target performance, crucial for the first physics analyses in the era of Super-BFactories. We will present the software framework for the detector calibration and alignment, the results from the first physics run and the prospects in view of the experience with the first data.

The Belle II experiment features a substantial upgrade of the Belle detector and will operate at the SuperKEKB energy-asymmetric e+e− collider at KEK in Tsukuba, Japan. The accelerator completed its first phase of commissioning in 2016, and the Belle II detector saw its first electron-positron collisions in April 2018. Belle II features a newly designed silicon vertex detector based on double-sided strip layers and DEPFET pixel layers. A subset of the vertex detector was operated in 2018 to determine background conditions (Phase 2 operation). The collaboration completed full detector installation in January 2019, and the experiment started full data taking. This paper will report on the final arrangement of the silicon vertex detector part of Belle II with a focus on online monitoring of detector conditions and data quality, on the design and use of diagnostic and reference plots, and on integration with the software framework of Belle II. Data quality monitoring plots will be discussed with a focus on simulation and acquired cosmic and collision data.

Background. Lifestyle interventions have shown to be effective when continuous personal support was provided. However, there is lack of knowledge whether a telemedical-approach with personal coaching contributes to long-term weight losses in overweight employees. We, therefore, tested the hypothesis that telemedical-based lifestyle interventions accompanied with telemedical coaching lead to larger weight losses in overweight persons in an occupational health care setting. Methods. Overweight employees (n=180) with a body mass index (BMI) of >27 kg/m2 were randomized into either a telemedical (TM) group (n=61), a telemedical coaching (TMC) group (n=58), or a control group (n=61). Both intervention groups were equipped with scales and pedometers automatically transferring the data into a personalized online portal, which could be monitored from participants and coaches. Participants of the TMC group received additionally one motivational care call per week by mental coaches to discuss the current data (current weight and steps) and achieving goals such as a healthy lifestyle or weight reduction. The control group remained in routine care. Clinical and anthropometric data were determined after the 12-week intervention. Additionally, weight change was followed up after 12 months. Results. Participants of TMC (-3.1 ± 4.8 kg, p