Erstellung einer Übersicht über die rechtlichen Regelungen zum ökologischen Landbau wichtiger Import- und Exportländer

Ziel des Projektes ist es, einen Überblick über die in wichtigen Import- und Exportländern geltenden gesetzlichen Regelungen und privatrechtlich Vereinbarungen zum ökologischen Landbau zu erstellen. Es wurde eine Datenbank entwickelt, die über die gesetzlichen Regelungen und die wichtigsten Verbandsrichtlinien für Ökoprodukte in den für Deutschland relevanten Import- und Exportländern informiert. Das Angebot beschreibt in leicht verständlicher Sprache die verschiedenen nationalen gesetzlichen Vorgaben für die Erzeugung, Verarbeitung, Kennzeichnung und Kontrolle von Ökoprodukten sowie deren Unterschiede zur EU-Öko-Verordnung. Darüber hinaus werden Richtlinien von Zertifizierungsorganisationen beschrieben, die eine marktbeherrschende Stellung in den lokalen Märkten einnehmen. Ergänzt wird das Angebot durch Originaltexte der Verordnungen und Richtlinien, soweit verfügbar in deutscher oder englischer Übersetzung sowie zahlreiche Adressen von Kontroll-/Zertifizierungsstellen und Behörden. Zielgruppen sind an Öko-Produkten interessierte Handels- und Verarbeitungsunternehmen sowie Beratungsorganisationen, Kontrollstellen und Behörden. Die Festlegung von Schwerpunktländern erfolgte auf Basis der Auswertung verfügbarer Import-/Export-Statistiken sowie einer schriftlichen Befragung ausgewählter Im- und Exportunternehmen für Öko-Produkte in Deutschland. Die Daten wurden in Form einer über das Internet verfügbaren Datenbank bereitgestellt. Die Datenbank wurde im Mai und Oktober 2003 aktualisiert

Modifiable risk factors associated with bone deficits in childhood cancer survivors

<p>Abstract</p> <p>Background</p> <p>To determine the prevalence and severity of bone deficits in a cohort of childhood cancer survivors (CCS) compared to a healthy sibling control group, and the modifiable factors associated with bone deficits in CCS.</p> <p>Methods</p> <p>Cross-sectional study of bone health in 319 CCS and 208 healthy sibling controls. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). Generalized estimating equations were used to compare measures between CCS and controls. Among CCS, multivariable logistic regression was used to evaluate odds ratios for BMD Z-score ≤ -1.</p> <p>Results</p> <p>All subjects were younger than 18 years of age. Average time since treatment was 10.1 years (range 4.3 - 17.8 years). CCS were 3.3 times more likely to have whole body BMD Z-score ≤ -1 than controls (95% CI: 1.4-7.8; p = 0.007) and 1.7 times more likely to have lumbar spine BMD Z-score ≤ -1 than controls (95% CI: 1.0-2.7; p = 0.03). Among CCS, hypogonadism, lower lean body mass, higher daily television/computer screen time, lower physical activity, and higher inflammatory marker IL-6, increased the odds of having a BMD Z-score ≤ -1.</p> <p>Conclusions</p> <p>CCS, less than 18 years of age, have bone deficits compared to a healthy control group. Sedentary lifestyle and inflammation may play a role in bone deficits in CCS. Counseling CCS and their caretakers on decreasing television/computer screen time and increasing activity may improve bone health.</p

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Hijacking a biosynthetic pathway yields a glycosyltransferase inhibitor within cells

Glycosyltransferases are ubiquitous enzymes that catalyze the assembly of glycoconjugates throughout all kingdoms of nature. A long-standing problem is the rational design of probes that can be used to manipulate glycosyltransferase activity in cells and tissues. Here we describe the rational design and synthesis of a nucleotide sugar analog that inhibits, with high potency both in vitro and in cells, the human glycosyltransferase responsible for the reversible post-translational modification of nucleocytoplasmic proteins with O-linked N-acetylglucosamine residues (O-GlcNAc). We show that the enzymes of the hexosamine biosynthetic pathway can transform, both in vitro and in cells, a synthetic carbohydrate precursor into the nucleotide sugar analog. Treatment of cells with the precursor lowers O-GlcNAc in a targeted manner with a single-digit micromolar EC50. This approach to inhibition of glycosyltransferases should be applicable to other members of this superfamily of enzymes and enable their manipulation in a biological setting.</p

Impaired Coronary and Renal Vascular Function in Spontaneously Type 2 Diabetic Leptin-Deficient Mice

<div><p>Background</p><p>Type 2 diabetes is associated with macro- and microvascular complications in man. Microvascular dysfunction affects both cardiac and renal function and is now recognized as a main driver of cardiovascular mortality and morbidity. However, progression of microvascular dysfunction in experimental models is often obscured by macrovascular pathology and consequently demanding to study. The obese type 2 diabetic leptin-deficient (ob/ob) mouse lacks macrovascular complications, i.e. occlusive atherosclerotic disease, and may therefore be a potential model for microvascular dysfunction. The present study aimed to test the hypothesis that these mice with an insulin resistant phenotype might display microvascular dysfunction in both coronary and renal vascular beds.</p><p>Methods and Results</p><p>In this study we used non-invasive Doppler ultrasound imaging to characterize microvascular dysfunction during the progression of diabetes in ob/ob mice. Impaired coronary flow velocity reserve was observed in the ob/ob mice at 16 and 21 weeks of age compared to lean controls. In addition, renal resistivity index as well as pulsatility index was higher in the ob/ob mice at 21 weeks compared to lean controls. Moreover, plasma L-arginine was lower in ob/ob mice, while asymmetric dimethylarginine was unaltered. Furthermore, a decrease in renal vascular density was observed in the ob/ob mice.</p><p>Conclusion</p><p>In parallel to previously described metabolic disturbances, the leptin-deficient ob/ob mice also display cardiac and renal microvascular dysfunction. This model may therefore be suitable for translational, mechanistic and interventional studies to improve the understanding of microvascular complications in type 2 diabetes.</p></div

Reaction times, learning, and executive functioning in adults born preterm

Abstract Background: This study examines cognitive functioning in adults born across the range of prematurity with appropriate or small for gestational age (SGA) birth weight compared with full-term controls. Methods: ESTER Preterm Birth Study participants without severe disabilities, comprising 133 early preterm (&lt;34 weeks, 17% SGA), 241 late preterm (34 + 0–36 + 6 weeks, 13% SGA), and 348 full-term subjects, performed the Cogstate® test at a mean age of 23.3 (SD = 1.2) years. Subtests measured paired associate learning, psychomotor function, executive function, spatial memory efficiency, visual memory, attention, working memory, visual learning, and emotional cognition. Data were analyzed with linear regression, full models adjusted for prenatal and postnatal factors and socioeconomic position. Results: Early preterm, late preterm, and full-term participants showed similar abilities in almost all subtests. Early preterm participants had 0.6 fewer moves/10 s (95% CI: −1.0; −0.2, full model) and late preterm and SGA participants had 1.3 fewer moves/10 s (95% CI: −2.1; −0.4) than full-term controls in the Groton Maze Learning Test, indicating weaker spatial memory efficiency. Conclusions: Adults born across the range of prematurity on average lack major defects in cognitive abilities. Cognitive problems may persist to adulthood only among those born the smallest: very preterm or preterm and SGA