Framework and baseline examination of the German National Cohort (NAKO)

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19–74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2–3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4–5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-022-00890-5

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (>= 65 years; estimated glomerular filtration rate <= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off <= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Influence of the microstructure on the cyclic stress-strain behaviour and fatigue life in hypo-eutectic Al-Si-Mg cast alloys

Aluminium alloys are promising candidates for energy-and cost-efficient components in automotive and aerospace industries, due to their excellent strength-to-weight ratio and relatively low cost compared to titanium alloys. As modern cast processing and post-processing, e.g. hot isostatic pressing, result in decreased frequency and size of defects, the weakest link depends on microstructural characteristics, e.g. secondary dendrite arm spacing (SDAS), Si eutectic morphology and α-Al solid solution hardness. Hereby, fatigue investigations of the effect of the microstructure characteristics on the cyclic stress-strain behaviour as well as fatigue mechanisms in the low cycle and high cycle fatigue regime are performed. For this purpose, samples of the aluminium cast alloy EN AC-AlSi7Mg0.3 with different Si eutectic morphology and α-Al solid solution hardness were investigated. To compare the monotonic and cyclic stress-strain curves, quasistatic tensile tests and incremental step tests were performed on two microstructure conditions. The results show that the cyclic loading leads to a hardening of the material compared to monotonic loading. Based on damage parameter Woehler curves, it is possible to predict the damage progression and fatigue life for monotonic and cyclic loading in hypo-eutectic Al-Si-Mg cast alloys by one power law

Influence of the microstructure on the cyclic stress-strain behaviour and fatigue life in hypo-eutectic Al-Si-Mg cast alloys

Aluminium alloys are promising candidates for energy-and cost-efficient components in automotive and aerospace industries, due to their excellent strength-to-weight ratio and relatively low cost compared to titanium alloys. As modern cast processing and post-processing, e.g. hot isostatic pressing, result in decreased frequency and size of defects, the weakest link depends on microstructural characteristics, e.g. secondary dendrite arm spacing (SDAS), Si eutectic morphology and α-Al solid solution hardness. Hereby, fatigue investigations of the effect of the microstructure characteristics on the cyclic stress-strain behaviour as well as fatigue mechanisms in the low cycle and high cycle fatigue regime are performed. For this purpose, samples of the aluminium cast alloy EN AC-AlSi7Mg0.3 with different Si eutectic morphology and α-Al solid solution hardness were investigated. To compare the monotonic and cyclic stress-strain curves, quasistatic tensile tests and incremental step tests were performed on two microstructure conditions. The results show that the cyclic loading leads to a hardening of the material compared to monotonic loading. Based on damage parameter Woehler curves, it is possible to predict the damage progression and fatigue life for monotonic and cyclic loading in hypo-eutectic Al-Si-Mg cast alloys by one power law

Influence of the microstructure on the cyclic stress-strain behaviour and fatigue life in hypo-eutectic Al-Si-Mg cast alloys

Aluminium alloys are promising candidates for energy-and cost-efficient components in automotive and aerospace industries, due to their excellent strength-to-weight ratio and relatively low cost compared to titanium alloys. As modern cast processing and post-processing, e.g. hot isostatic pressing, result in decreased frequency and size of defects, the weakest link depends on microstructural characteristics, e.g. secondary dendrite arm spacing (SDAS), Si eutectic morphology and α-Al solid solution hardness. Hereby, fatigue investigations of the effect of the microstructure characteristics on the cyclic stress-strain behaviour as well as fatigue mechanisms in the low cycle and high cycle fatigue regime are performed. For this purpose, samples of the aluminium cast alloy EN AC-AlSi7Mg0.3 with different Si eutectic morphology and α-Al solid solution hardness were investigated. To compare the monotonic and cyclic stress-strain curves, quasistatic tensile tests and incremental step tests were performed on two microstructure conditions. The results show that the cyclic loading leads to a hardening of the material compared to monotonic loading. Based on damage parameter Woehler curves, it is possible to predict the damage progression and fatigue life for monotonic and cyclic loading in hypo-eutectic Al-Si-Mg cast alloys by one power law

Non-invasive imaging of bioresorbable coronary scaffolds using CT and MRI: First in vitro experience

Background: Accurate assessment of coronary stents after PCI using non-invasive imaging remains challenging despite technological improvements. New bioresorbable vascular scaffolds (BVS) have recently become available promising improved non-invasive imaging properties, which however have not be examined specifically yet. Therefore we investigated CT and MRI visualization properties of the only two CE-marked coronary BVSs. Methods: The Abbott Absorb and the Elixir DESolve BVS were placed in plastic tubes filled with contrast agent and scanned with a latest generation CT respectively MR system. For CT image quality was assessed by two blinded, independent readers and in-scaffold diameter difference as well as in-scaffold attenuation difference were measured. For MRI in-scaffold signal intensity, in-scaffold lumen visibility and in-scaffold signal homogeneity were measured. Results: In CTA both BVSs showed no significant difference to nominal tube diameter (DESolve 101%, Absorb 100%) and to nominal tube attenuation (DESolve 96%, Absorb 98%) and were both rated with the highest score for unrestricted lumen visualization. In MRA both BVSs showed unimpaired signal intensity (DESolve 103%, Absorb 100%), lumen visibility (DESolve 92%, Absorb 89%) and lumen homogeneity (DESolve SD 7.1%, Absorb SD 9.5%) when compared to the unstented tube. There was no significant difference between CTA and MRA results of both BVSs. Conclusions: Coronary BVSs show no relevant impairment for subjective and objective measures of in-stent lumen visualization by CT and MRI and will therefore allow reliable non-invasive assessment of coronary artery patency after PCI with deployment of a BVS, which is an (additional) advantage when compared to conventional stents. (C) 2016 Elsevier Ireland Ltd. All rights reserved

In TFIIH, XPD Helicase Is Exclusively Devoted to DNA Repair

The eukaryotic XPD helicase is an essential subunit of TFIIH involved in both transcription and nucleotide excision repair (NER). Mutations in human XPD are associated with several inherited diseases such as xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. We performed a comparative analysis of XPD from Homo sapiens and Chaetomium thermophilum (a closely related thermostable fungal orthologue) to decipher the different molecular prerequisites necessary for either transcription or DNA repair. In vitro and in vivo assays demonstrate that mutations in the 4Fe4S cluster domain of XPD abrogate the NER function of TFIIH and do not affect its transcriptional activity. We show that the p44-dependent activation of XPD is promoted by the stimulation of its ATPase activity. Furthermore, we clearly demonstrate that XPD requires DNA binding, ATPase, and helicase activity to function in NER. In contrast, these enzymatic properties are dispensable for transcription initiation. XPD helicase is thus exclusively devoted to NER and merely acts as a structural scaffold to maintain TFIIH integrity during transcription