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Dwarf caimans (Alligatoridae: Paleosuchus palpebrosus and Paleosuchus trigonatus), are small crocodilians exhibiting cryptic behaviour and complex habitat use that occur throughout the Amazon region. Our goals were to evaluate individual home range, habitat occupancy and movement patterns where they occur in sympatry in relation to seasonal water-level variation. We tracked five P. palpebrosus and seven P. trigonatus using VHS radio transmitters along the shores of two streams directly influenced by the flooding pulse of the Purus River. Paleosuchus palpebrosus individuals moved greater distances on a daily basis and had larger home ranges than P. trigonatus, and the species had different responses to increases in water levels. Paleosuchus palpebrosus moved into flooded forests, as do their principle prey species. Conversely, larger P. trigonatus individuals usually remained near the main stream, and were relatively sedentary. Intraspecific home-range overlap was higher than interspecific overlap in both species. Thus, habitat occupancy patterns as a function of water-level variation might facilitate coexistence of the two species of dwarf caimans in the same location. This study shows that when living in sympatry under a seasonal flooding regime, Paleosuchus species show a degree of habitat partitioning evidenced by different daily movement rates, home- range sizes and home-range locations

We review the extent and nature of scientific knowledge of the Big-headed Amazon River Turtle, Peltocephalus dumerilianus, covering distribution, morphology, taxonomy, diet, behaviour, reproduction, and ecology. We discuss the phylogenetic position of the species and its evolutionary relationships with the other podocnemidids, comparing morphological, karyological and molecular information. Also, we describe the importance of this species and its relationship with traditional Amazonian communities, including capture techniques, uses, beliefs and taboos. Finally, we comment on the conservation status of the species and the urgent need for additional studies. Besides discussing and reinterpreting published data, we provide new information from recent genetic studies, field activities and captive observations.

Posterior urethral valves (PUV) are the most common form of lower urinary tract obstructions (LUTO). The valves can be surgically corrected postnatally; however, the impairment of kidney and bladder development is irreversible and has lifelong implications. Chronic kidney disease (CKD) and bladder dysfunction are frequent problems. Approximately 20% of PUV patients will reach end-stage kidney disease (ESKD). The subvesical obstruction in PUV leads to muscular hypertrophy and fibrotic remodelling in the bladder, which both impair its function. Kidney development is disturbed and results in dysplasia, hypoplasia, inflammation and renal fibrosis, which are hallmarks of CKD. The prognoses of PUV patients are based on prenatal and postnatal parameters. Prenatal parameters include signs of renal hypodysplasia in the analysis of fetal urine. Postnatally, the most robust predictor of PUV is the nadir serum creatinine after valve ablation. A value that is below 0.4 mg/dL implies a very low risk for ESKD, whereas a value above 0.85 mg/dL indicates a high risk for ESKD. In addition, bladder dysfunction and renal dysplasia point towards an unbeneficial kidney outcome. Experimental urinary markers such as MCP-1 and TGF-β, as well as microalbuminuria, indicate progression to CKD. Until now, prenatal intervention may improve survival but yields no renal benefit. The management of PUV patients includes control of bladder dysfunction and CKD treatment to slow down progression by controlling hypertension, proteinuria and infections. In kidney transplantation, aggressive bladder management is essential to ensure optimal graft survival.

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The efficacy of convalescent plasma for COVID-19 is unclear. While most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content may influence patient outcomes.We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 days of respiratory symptom onset. Patients were allocated 2:1 to 500 mL of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 days. The effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression.The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. 940 patients were randomized and 921 patients were included in the intent-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) in the convalescent plasma arm and 86/307 (28.0%) in the standard of care arm; relative risk (RR) 1.16 (95% confidence interval (CI) 0.94-1.43; p=0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% vs. 26.4%; RR=1.27, 95% CI 1.02-1.57, p=0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standard log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (OR=0.74; 0.57-0.95 and OR=0.66; 0.50-0.87, respectively), while IgG against the full transmembrane Spike protein increased it (OR=1.53, 95% CI 1.14-2.05).Convalescent plasma did not reduce the risk of intubation or death at 30 days among hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavourable antibody profiles may be associated with worse clinical outcomes compared to standard care.Trial registrationCONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1); NCT04348656; https://www.clinicaltrials.gov/ct2/show/NCT04348656

The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care., A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

Industrieunternehmen befinden sich derzeit in einem Transformationsprozess zu nachhaltigen, beispielsweise klimaneutralen Unternehmen. Die zentrale Herausforderung liegt dabei in der Identifikation von Ma��nahmen mit m��glichst gro��em Nachhaltigkeitseffekt zu m��glichst geringen Kosten, damit der Unternehmenserfolg zu keinem Zeitpunkt gef��hrdet ist. Im Rahmen dieser Arbeit wurde ein Entscheidungsunterst��tzungssystem entwickelt, mit dem industrielle Wertsch��pfungsketten klimafreundlicher und zugleich wirtschaftlich konfiguriert werden k��nnen. Eine Anwendung erfolgt in Fallstudien zur Automobil- und Zulieferindustrie.

System xc- ist ein Cystin-Glutamat-Antiporter, der im Menschen vor allem in Zellen des zentralen Nervensystems vorkommt. Insbesondere in Astrozyten ist er sehr ausgeprägt exprimiert. System xc- tauscht Glutamat (Glu) und Cystin im Verhältnis 1:1 aus. Dieser Austausch ist prinzipiell in beiden Richtungen möglich. In vivo wird aufgrund der Konzentrationsgradienten Glutamat exportiert und Cystin importiert. Cystin ist das limitierende Substrat der Glutathionsynthese. Glutathion (GSH) ist das wichtigste Antioxidanz des Körpers und dient somit dem Schutz der Zelle vor oxidativem Stress - dem Ungleichgewicht zwischen freien Sauerstoffradikalen (ROS) und Antioxidanzien. Oxidativer Stress führt zur Schädigung von Proteinen, Lipiden und DNA und trägt zur Alterung der Zellen bei. Diese führt zur Entstehung neurodegenerativer Erkrankungen wie der Parkinson- und Alzheimer-Erkrankung der Amyotrophen Lateralsklerose und der Multiplen Sklerose. Während eine System xc--Induktion gegen oxidativen Stress durch Steigerung der GSH-Synthese protektiv wirkt, hat die Induktion auch Schattenseiten. Im zentralen Nervensystem ist System xc- hauptverantwortlich für extrasynaptisches Glutamat. Eine zu hohe extrazelluläre Glu-Konzentration kann zu Exzitotoxizität führen. Dabei entsteht durch Übererregung der NMDA-Rezeptoren ein Calcium-Einstrom, der zum Zelltod führt und an der Pathogenese von Epilepsien, Multipler Sklerose, der Amyotophen Lateralsklerose und der Chorea Huntington beteiligt ist. System xc- wird durch oxidativen Stress, Schwermetalle und Elektrophile über den Transkriptionsfaktor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) und bei Aminosäuremangel über den aktivierenden Trankriptionsfaktor 4 (ATF4) hochreguliert. Weiterhin sind einige mit Entzündung assoziierte Induktoren wie Interleukin 1β, Lipoploysaccharide und Tumornekrosefaktor α (TNF-α) bekannt Dabei ist der genaue Mechanismus noch ungeklärt ist. Die Induktion durch TNF-α wurde in dieser Arbeit untersucht. Die Experimente wurden mit primären murinen Astrozyten und mit murinen embryonalen Fibroblasten (MEF) durchgeführt. Letztere wurden als Modell verwendet, da knock-out-Zelllinien in der Regel nur als MEF zur Verfügung standen. Die System xc--Aktivität wurde funktionell mittels eines Glu-Aufnahmeassays mit radioaktiv markiertem L-[3H]-Glu bestimmt. System xc- wird sowohl in primären Astrozyten als auch in MEF über den TNF-α-Rezeptor 1 zeit- und konzentrationsabhängig induziert. Der zeitliche Verlauf deutete auf einen transkriptionellen Mechanismus hin. Der Transkriptionsfaktor Nrf2 ist essentiell für die TNF-α-vermittelte System xc-- Induktion. In Nrf2-/- MEF ließ sich die System xc--Aktivität nicht mehr durch TNF-α induzieren. Die pharmakologische Inhibition von nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NF-κB) sowie Inhibitor von κB-Kinase beta(IKKbeta)-Defizienz führten zu einer Steigerung der System xc--Aktivität. Dies könnte durch den hemmenden Einfluss von NF-κB auf den Nrf2-Signalweg erklärt werden. Bei p38-Inhibition konnte eine Steigerung der Induktion gesehen werden, die darauf zurückzuführen sein könnte, dass p38 hemmende Effekte auf den Nrf2-Signalweg hat. Gegenteilig dazu erzielte eine Inhibition der durch extrazelluläres Signal regulierten Kinasen (ERK1/2) eine Hemmung der TNF-α vermittelten System xc--Induktion. Dies könnte durch die Nrf2-Induktion durch ERK1/2 zu erklären sein. Auf den ersten Blick scheint die System xc--Induktion ein vorteilhafter Mechanismus, um dem ROS-induzierten oxidativen Stress entgegenzuwirken. Allerdings werden durch die Induktion Probleme in Gestalt der Glu-induzierten Exizitotoxizität geschaffen. In verschiedenen Tiermodellen konnte gezeigt werden, dass die System xc--Induktion die Progression neurodegenerativer Erkrankungen fördert. Als mögliche Gegenmaßnahme zur System xc--induzierten Exzitotoxizität kommt die Induktion exzitatorischer Aminosäuretransporter (EAAT) in Frage. Die System xc--Induktion im Rahmen einer ZNS-Inflammation scheint an der Entstehung und Progression neurodegenerativer Erkrankungen - am ehesten durch Glu-bedingte Exzitotoxizität - beteiligt zu sein. Eine zusätzliche pharmakologische Steigerung scheint deshalb nicht erstrebenswert. System xc--Inhibition kommt bei Neuroinflammation als therapeutisches Ziel in Frage, dazu müsste aber der Signalweg abschließend bekannt sein.

Em razão da falta de material específico de consulta que consolide as principais referências científicas e o acúmulo do conhecimento técnico sobre as metodologias de amostragem, coleta e análise de dados relativos aos quelônios continentais brasileiros, materializou-se este trabalho, há muito almejado pela sociedade interessada no assunto. Houve um grande esforço para compatibilizar metodologicamente as particularidades das espécies e ambientes em áreas com lacunas de amostragem, cujos parâmetros se adequam prioritariamente aos inventários e, em áreas com ocorrência conhecida de espécie(s) alvo de estudos de maior duração, aos monitoramentos populacionais. Sendo assim, essencialmente, este guia metodológico ou manual técnico inédito se constitui em roteiros de procedimentos fundamentados pela consolidação do estado da arte do conhecimento técnico-científico e pelas perspectivas, harmonizadas, dos principais grupos de pesquisa e entidades conservacionistas que atuam com esses animais. Essa iniciativa é oportuna, pois favorecerá a tão esperada padronização instrumental e analítica, segundo orientações validadas pelas experiências práticas dos autores, a serem adotados de forma consonante por diversas instituições ou grupos de pesquisa. Em consequência, poder-se-á integrar diferentes bancos de dados, compilar informações de séries históricas de dados de projetos correlatos, e assim, desenvolver análises comparativas das variáveis decorrentes dos componentes de pesquisa e conservação realizados de forma sistematizada por espécie, família, região, bioma etc., por meio de diferentes fontes de informação. E ainda, esta publicação tem o propósito de estimular a realização de estudos de caracterização do estado de conservação do grupo animal foco, especialmente em áreas protegidas, por meio da promoção de pesquisas básicas relativas à dinâmica de suas populações.