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Cryopyrin-associated periodic syndromes (CAPS) are orphan hereditary auto-inflammatory diseases with various phenotypes, including chronic kidney disease (CKD). Current therapies inhibit interleukin-1 (IL-1) to achieve clinical and serological remission; however, the effect on kidney involvement remains unclear. The objective of this study was to investigate the long-term efficacy of anti-IL-1 treatment with special emphasis on renal outcome. We retrospectively analysed clinical, genetic and laboratory data of patients with CAPS under anti-IL-1 therapy from a single-centre university outpatient clinic. Patients with CAPS (n = 28) were followed for a median of 11 (IQR 8.5–13) years. Four patients at various ages (19%), bearing the most common CAPS mutation R260W, had significant CKD at presentation. All affected patients were related; however, other family members with the same genetic variant did not develop CKD. While anti-IL-1 therapy was effective in lowering symptom burden and inflammatory parameters in all CAPS patients, two of the four individuals with significant CKD had persistent proteinuria and worsening kidney function. None of the patients without renal affection at therapy initiation developed relevant CKD in the follow-up period. We showed that in patients with CAPS: (1) CKD is a common complication; (2) renal involvement shows familial predisposition beyond the mutational status and is independent of age; (3) anti-IL-1 therapy results in sustained improvement of inflammatory parameters and symptom load and (4) may prevent development of CAPS-associated CKD but not affect kidney involvement when already present. Overall, early therapy initiation might sufficiently prevent renal disease manifestation and attenuate progression. [ABSTRACT FROM AUTHOR]

To investigate clinical symptoms and genetic variants in patients from the German anti-IL-1 registry for autoinflammatory orphan diseases (GARROD) between 2013 and 2022. Multicentre, retrospective analysis of demographic, clinical and genetic data of patients with autoinflammatory diseases (AID) who received anti-IL-1 targeted therapy. The cohort comprised 152 patients with familial Mediterranean fever (FMF; n = 71), cryopyrin-associated periodic syndromes (CAPS; n = 43), TNF-receptor associated periodic syndrome (TRAPS; n = 19), mevalonate kinase deficiency (MKD; n = 3) and unclassified AID (uAID; n = 16). Inflammatory attacks started in 61.2% of the patients before the age of 18 years. The delay between the first AID attack and anti-IL-1 therapy was 17.8 years. Monogenetic AIDs were diagnosed by clinical symptoms. Genetic analyses confirmed the diagnosis in 87.3% of patients with FMF, 65.2% with CAPS and 94.8% with TRAPS. Among this group, heterozygous MEFV variants and variants of unknown significance (VUS) were detected in 22.5% of patients with FMF, 51.2% with CAPS and 47.4% with TRAPS. Patients with VUS were older at disease onset which is consistent with a milder phenotype. Twenty-four patients had secondary AA amyloidosis (AA) at initiation of anti-IL-1 therapy. The mean age of these patients was 16.4 years at their first attack and 44.9 years at the time of AA diagnosis. Turkish-Armenian ancestry correlated with MEFV variants and higher FMF disease activity compared to German ancestry. Molecular genetic analyses should substantiate the clinical diagnosis of a monogenetic AID. Our data support the concept of variable penetrance of VUS which can be associated with late-onset AID. [ABSTRACT FROM AUTHOR]

Airborne laser scanners (ALS) are used to map the sea-ice surface at sub-meter resolution. We conducted 64 flights over the Arctic sea ice between September 2019 and September 2020 during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition to measure sea-ice surface elevation. The flights ranged from repeated, local-scale 5 × 5 km2 floe grid surveys to regional-scale transects more than 100 km long. We provide data at different processing levels: geolocated elevation point clouds and gridded segments of elevation and freeboard with a spatial resolution of 0.5 m. The latter product is corrected for atmospheric backscatter, sea-ice drift, and offset in elevation due to degraded INS/GNSS solutions > 85° N. For floe grid surveys, all data are combined to merged two-dimensional elevation maps. Other provided parameters include laser reflectance and echo width. The presented data offer a unique possibility to study the temporal evolution, spatial distribution, and variability of the snow and sea-ice surface and their properties in addition to validating satellite products. [ABSTRACT FROM AUTHOR]

This paper develops a principal-agent model with adverse selection to analyse firms' decisions between an existing carbon-intensive technology and a new low-carbon technology requiring an externally funded initial investment. We find that a Pigouvian emission tax alone may result in credit rationing and under-investment in low-carbon technologies. Combining the Pigouvian tax with interest subsidies or loan guarantees resolves credit rationing and yields a first-best outcome. An emission tax set above the Pigouvian level can also resolve credit rationing and, in some cases, yields a first-best outcome. If a carbon price is (politically) not feasible, intervention on the credit market alone can promote low-carbon development. However, such a policy yields a second-best outcome. The issue of credit rationing is temporary if the risks of low-carbon technologies decline. However, there are social costs of delay if credit rationing is not addressed. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is very common in hospitalized patients, affecting patient's mortality and morbidity. Major causes are prerenal AKI and acute tubular necrosis (ATN). Even though a variety of parameters/indices exist, their reliability and practicability are controversial: in fact, there is a need for a simple diagnostic approach for AKI in in-patients with parameters easily obtained in any hospital. The objective of the study was: (1) to assess reliability of simple laboratory parameters/indices to differentiate pre-/intrarenal AKI; (2) to evaluate the most reliable and feasible parameters/indices; and (3) to identify the possible impact of confounding factors. Retrospectively, in-patients with AKI hospitalized in 2020 in a university nephrology department were included. Spot urine and 24-h collection urine was analyzed with urine sodium (UNa), urine specific gravity (USG), fractional excretion of sodium (FENa), fractional excretion of urea (FEUrea), urine osmolality (UOsm), urine to plasma creatinine ratio (UCr/PCr) and renal failure index (RFI). Overall, 431 patients were included. UNa, UOsm, USG and RFI showed high specificity > 85% for prerenal AKI, UNa and RFI provided good specificity for ATN. Loop diuretics, ACE inhibitors/AT1 blockers or pre-existing chronic kidney disease had no impact. In patients with AKI, UNa, USG and RFI: (1) proved to be very specific for prerenal AKI and showed high sensitivity for ATN; (2) can be easily determined using serum and spot urine; and (3) are not confounded by medication or comorbidities. These parameters/indices are helpful to identify the aetiology of AKI and to guide therapy, thereby improving patients' safety and outcome. [ABSTRACT FROM AUTHOR]

The Multidisciplinary Drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition took place between October 2019 and September 2020 giving the rare opportunity to monitor sea-ice properties over a full annual cycle. Here we present 24 high-resolution orthomosaics and 14 photogrammetric digital elevation models of the sea-ice surface around the icebreaker RV Polarstern between March and September 2020. The dataset is based on >34.000 images acquired by a helicopter-borne optical camera system with survey flights covering areas between 1.8 and 96.5 km2 around the vessel. Depending on the flight pattern and altitude of the helicopter, ground resolutions of the orthomosaics range between 0.03 and 0.5 m. By combining the photogrammetric products with contemporaneously acquired airborne laser scanner reflectance measurements selected orthomosaics could be corrected for cloud shadows which facilitates their usage for sea-ice and melt pond classification algorithms. The presented dataset is a valuable data source for the interdisciplinary MOSAiC community building a temporal and spatially resolved baseline to accompany various remote sensing and in situ research projects. [ABSTRACT FROM AUTHOR]

Copyright of Die Pathologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Die Pathologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Sea ice continues to decline across many regions of the Arctic, with remaining ice becoming increasingly younger and more dynamic. These changes alter the habitats of microbial life that live within the sea ice, which support healthy functioning of the marine ecosystem and provision of resources for human-consumption, in addition to influencing biogeochemical cycles (e.g. air–sea CO2 exchange). With the susceptibility of sea ice ecosystems to climate change, there is a pressing need to fill knowledge gaps surrounding sea ice habitats and their microbial communities. Of fundamental importance to this goal is the development of new methodologies that permit effective study of them. Based on outcomes from the DiatomARCTIC project, this paper integrates existing knowledge with case studies to provide insight on how to best document sea ice microbial communities, which contributes to the sustainable use and protection of Arctic marine and coastal ecosystems in a time of environmental change. [ABSTRACT FROM AUTHOR]

Microsecretory adenocarcinoma (MSA) of the salivary glands is a recently described entity. Due to lack of reported metastases, in 30 cases described until now, the designation as low-grade cancer was so far solely based on demonstration of local tumor invasion and in a single case with perineural invasion. We herein describe the first documented case with local recurrence and hematogenous metastases. [ABSTRACT FROM AUTHOR]

The light-driven formation and cleavage of cyclobutane structural motifs resulting from [2 + 2]-pericyclic reactions, as found in thymine and coumarin-type systems, is an important and intensively studied photochemical reaction. Various applications are reported utilizing these systems, among others, in cross-linked polymers, light-triggered drug release, or other technical applications. Herein coumarin is most frequently used as the photoactive group. Quite often, a poor quantum yield for dimerization and cyclobutane-cleavage and a lack of reversibility are described. In this work, we present the identification of a heterogeneous pathway of dimer cleavage found in a rarely studied coumarin analog molecule, the N-methyl-quinolinone (NMQ). The monomer was irradiated in a tube flow-reactor and the reaction process was monitored using online HPLC measurements. We found the formation of a pseudo-equilibrium between monomeric and dimeric NMQ and a continuous rise of a side product via oxidative dimer splitting and proton elimination which was identified as 3,3'-bis-NMQ. Oxidative conversion by singlet oxygen was identified to be the cause of this non-conventional cyclobutane cleavage. The addition of antioxidants suppressing singlet oxygen enables achieving a 100% photochemical conversion from NMQ to the anti-head-to-head-NMQ-dimer. Using dissolved oxygen upon light activation to singlet oxygen limits the reversibility of the photochemical [2 + 2]-cycloaddition and cycloreversion of NMQ and most likely comparable systems. Based on these findings, the development of highly efficient cycloaddition–cycloreversion systems should be enabled. [ABSTRACT FROM AUTHOR]

Two-Sided Matching is a widely used approach to allocate resources based on preferences. In Two-Sided Matching problems where indifferences are allowed in the preference lists, finding stable matchings with certain properties is known to be NP-hard and, in some instances, even NP-hard to approximate. This article, therefore, considers the use of heuristics in Two-Sided Matching scenarios with indifferences to find and explore potential solutions and their properties. Two heuristics, a Genetic Algorithm and Threshold Accepting, are compared to existing approaches with respect to their ability to generate alternative stable solutions based on initially stable matchings for scenarios with either complete or incomplete preferences. The evaluation shows that using these types of heuristics is a valid approach to obtain matchings with improved properties such as fairness or average matched rank, compared to existing algorithms. Overall, this approach allows for the exploration of alternative stable matchings and subsequent selection of a best solution given selected evaluation criteria. [ABSTRACT FROM AUTHOR]

Various topographically heterogeneous, histologically related groups of basaloid tumours are characterized by ghost cell differentiation with associated CTNNB1 mutations and nuclear β-catenin expression. We describe the unique case of a malignant tumour with ghost cell differentiation in the floor of the mouth, in which clinical, radiological, histological, immunohistological and molecular data altogether strongly indicate classification as a new type of salivary gland carcinoma. [ABSTRACT FROM AUTHOR]

Hydrocortisone (HC) substitution is essential in the treatment for patients with adrenal insufficiency (AI). Current replacement regimens however only incompletely mimic the physiological circadian rhythm of cortisol secretion, thereby resulting in subclinical temporary hypo- and hypercortisolism. Several studies point toward impairment of cognitive functions under these conditions, in part due to affected catecholamine secretion. Aim of this study was to evaluate the influence of long-term versus short-term HC replacement therapy on the adrenomedullary system and cognitive functions. Fourteen patients with primary or secondary AI were divided into two groups, depending on the duration of disease and HC replacement therapy (<15 years). All subjects underwent standardized neurocognitive testing; in addition, cortisol and catecholamine levels as well as physiological parameters and quality of life (QoL) were assessed. Patients with HC replacement therapy ≥15 years (n = 7) received significantly higher equivalent glucocorticoid doses than those with a shorter lasting therapy (n = 7; p = 0.048). Neuropsychological tests, QoL, physiological parameters, and cortisol levels did not differ significantly between both groups. Of note, norepinephrine levels were significantly lower in patients on short-term HC replacement therapy ( p = 0.025). However, there were no significant differences in catecholamines with respect to the underlying pathophysiology, gender, or age. Irrespective of the duration of use, male patients scored significantly better for single aspects of QoL, whereas females performed significantly better in the attention test. Overall, we showed that duration of cortisol replacement therapy may have an impact on catecholamine release, but does not seem to affect cognitive functions and QoL. [ABSTRACT FROM AUTHOR]

During the winter and spring of 2006, we investigated the sea ice physics and marine biology in the northwest Weddell Sea, Antarctica aboard R/V Polarstern. We determined the texture of each ice core and 71 ice crystal thin sections from 27 ice cores. We analyzed 393 ice cores, their temperatures, 348 block density and salinity samples, and 311 chlorophyll a (Chl a) and phaeophytin samples along the cruise route during the investigation. Based on the vertical distributions of 302 groups of data for the ice porosity and Chl a content in the ice at the same position, we obtained new evidence that ice physical parameters influence the Chl a content in ice. We collected snow and ice thickness data, and established the effects of the snow and ice thickness on the Chl a blooms under the ice, as well as the relationships between the activity of ice algae cells and the brine volume in ice according to the principle of environmental control of the ecological balance. We determined the upper limits for Chl a in the brine volume of granular and columnar ice in the Antarctica, thereby demonstrating the effects of ice crystals on brine drainage, and the contributions of the physical properties of sea ice to Chl a blooms near the ice bottom and on the ice-water interface in the austral spring. Moreover, we found that the physical properties of sea ice affect ice algae and they are key control elements that modulate marine phytoplankton blooms in the ice-covered waters around Antarctica. [ABSTRACT FROM AUTHOR]

Copyright of Medizinische Klinik (Urban & Vogel) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The microfibrillar protein fibrillin-1 is expressed abundantly in the vasculature and the glomerulus of the kidney. Mutations in the fibrillin-1 gene lead to Marfan syndrome. The most common complication of this disease is aortic dilatation due to elastic deficiencies of the vascular wall. Several case reports describe glomerular disease in patients with Marfan syndrome, and fibrillin-1 has been implicated in nephrogenesis. To study the role of fibrillin-1 in renal development and function, we characterized the renal phenotype of fibrillin-1-underexpressing mice. Kidney histology was evaluated by means of morphometry and stereology. Relative kidney weights, daily urine excretion, urinary albumin excretion, serum and urinary creatinine, as well as serum urea were not different than wild-type mice. Glomerular number and renal capillarization were normal. The size of the renal filtration surface was comparable in wild-type and fibrillin-1-underexpressing mice. There was no indication for glomerular, renal vascular, or tubulointerstitial injury. However, glomerular volume and mesangial area were reduced. No changes in glomerular cell numbers were detected, but the cellular volume of mesangial cells was significantly lower in glomeruli of fibrillin-1-underexpressing mice. Thus, despite the high abundance of fibrillin-1 in glomeruli of wild-type animals, underexpression of fibrillin-1 did not lead to functional deficiencies of the glomerulus. Alterations in renal histology were only subtle with a reduced glomerular volume and mesangial area likely due to a reduced mesangial cell volume. [ABSTRACT FROM AUTHOR]

Although the calcium requirement of phytochrome-mediated fern spore germination and early rhizoid growth is well established, the calcium-binding proteins that serve as transducers for these responses are not known. Here we report the presence of annexin-like proteins in germinating spores of Dryopteris filix-mas (L.) Schott and Anemia phyllitidis (L.) Sw. and evidence that they may be important participants in early photomorphogenic changes in gametophytes. Immunolocalization and immunoblot assays of these proteins were carried out using polyclonal antibodies raised either against a 35-kDa annexin-like protein from pea or against anchorin CII from chicken. Western-blot analysis showed that crude protein extracts obtained from both species after red-light treatment contained two cross-reactive protein bands with molecular weights around 70 kDa. These proteins were annexin-like in that they bound to a phosphatidylserine affinity column in a calcium-dependent fashion. Using this column, two protein bands around 70 kDa, i.e. 67 and 73 kDa, were partially purified together with proteins at 36 kDa and a doublet at 54 kDa. Proteins of these latter molecular weights are suggested to be members of the annexin family, but no cross-reactivity could be found between these and the two antibodies used in our investigations. Immunodetectable levels of these proteins were observed only after light-mediated induction of spore germination. Imaging of the immuno-localization patterns observed with both antibodies showed that the annexin-like proteins are concentrated at the extreme tips of the rhizoids in D. filix-mas and A. phyllitidis during rhizoid initiation and all stages of elongation. We suggest that these proteins may play a major role in the tip-oriented exocytosis events that are critical for the initiation and growth of fern rhizoids. [ABSTRACT FROM AUTHOR]

Bicyclic peptides have great therapeutic potential since they can bridge the gap between small molecules and antibodies by combining a low molecular weight of about 2 kDa with an antibody-like binding specificity. Here we apply a recently developed in silico rational design strategy to produce a bicyclic peptide to target the C-terminal region (residues 31–42) of the 42-residue form of the amyloid β peptide (Aβ42), a protein fragment whose aggregation into amyloid plaques is linked with Alzheimer's disease. We show that this bicyclic peptide is able to remodel the aggregation process of Aβ42 in vitro and to reduce its associated toxicity in vivo in a C. elegans worm model expressing Aβ42. These results provide an initial example of a computational approach to design bicyclic peptides to target specific epitopes on disordered proteins. [ABSTRACT FROM AUTHOR]

Sea ice is an important transport vehicle for gaseous, dissolved and particulate matter in the Arctic Ocean. Due to the recently observed acceleration in sea ice drift, it has been assumed that more matter is advected by the Transpolar Drift from shallow shelf waters to the central Arctic Ocean and beyond. However, this study provides first evidence that intensified melt in the marginal zones of the Arctic Ocean interrupts the transarctic conveyor belt and has led to a reduction of the survival rates of sea ice exported from the shallow Siberian shelves (−15% per decade). As a consequence, less and less ice formed in shallow water areas (<30 m) has reached Fram Strait (−17% per decade), and more ice and ice-rafted material is released in the northern Laptev Sea and central Arctic Ocean. Decreasing survival rates of first-year ice are visible all along the Russian shelves, but significant only in the Kara Sea, East Siberian Sea and western Laptev Sea. Identified changes affect biogeochemical fluxes and ecological processes in the central Arctic: A reduced long-range transport of sea ice alters transport and redistribution of climate relevant gases, and increases accumulation of sediments and contaminates in the central Arctic Ocean, with consequences for primary production, and the biodiversity of the Arctic Ocean. [ABSTRACT FROM AUTHOR]