Epoetin Beta and C-Terminal Fibroblast Growth Factor 23 in Patients With Chronic Heart Failure and Chronic Kidney Disease

Background In patients with chronic heart failure and chronic kidney disease, correction of anemia with erythropoietin-stimulating agents targeting normal hemoglobin levels is associated with an increased risk of cardiovascular morbidity and mortality. Emerging data suggest a direct effect of erythropoietin on fibroblast growth factor 23 (FGF23), elevated levels of which have been associated with adverse outcomes. We investigate effects of erythropoietin-stimulating agents in patients with both chronic heart failure and chronic kidney disease focusing on FGF23. Methods and Results In the EPOCARES (Erythropoietin in CardioRenal Syndrome) study, we randomized 56 anemic patients (median age 74 [interquartile range 69-80] years, 66% male) with both chronic heart failure and chronic kidney disease into 3 groups, of which 2 received epoetin beta 50 IU/kg per week for 50 weeks, and the third group served as control. Measurements were performed at baseline and after 2, 26, and 50 weeks. Data were analyzed using linear mixed-model analysis. After 50 weeks of erythropoietin-stimulating agent treatment, hematocrit and hemoglobin levels increased. Similarly, C-terminal FGF23 levels, in contrast to intact FGF23 levels, rose significantly due to erythropoietin-stimulating agents as compared with the controls. During median follow-up for 5.7 (2.0-5.7) years, baseline C-terminal FGF23 levels were independently associated with increased risk of mortality (hazard ratio 2.20; 95% CI, 1.35-3.59; P=0.002). Conclusions Exogenous erythropoietin increases C-terminal FGF23 levels markedly over a period of 50 weeks, elevated levels of which, even at baseline, are significantly associated with an increased risk of mortality. The current results, in a randomized trial setting, underline the strong relationship between erythropoietin and FGF23 physiology in patients with chronic heart failure and chronic kidney disease. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00356733

Design of a consensus-based geriatric assessment tailored for older chronic kidney disease patients: results of a pragmatic approach

Purpose Unidentified cognitive decline and other geriatric impairments are prevalent in older patients with advanced chronic kidney disease (CKD). Despite guideline recommendation of geriatric evaluation, routine geriatric assessment is not common in these patients. While high burden of vascular disease and existing pre-dialysis care pathways mandate a tailored geriatric assessment, no consensus exists on which instruments are most suitable in this population to identify geriatric impairments. Therefore, the aim of this study was to propose a geriatric assessment, based on multidisciplinary consensus, to routinely identify major geriatric impairments in older people with advanced CKD. Methods A pragmatic approach was chosen, which included focus groups, literature review, inventory of current practices, an expert consensus meeting, and pilot testing. In preparation of the consensus meeting, we composed a project team and an expert panel (n = 33), drafted selection criteria for the selection of instruments, and assessed potential instruments for the geriatric assessment. Results Selection criteria related to general geriatric domains, clinical relevance, feasibility, and duration of the assessment. The consensus-assessment contains instruments in functional, cognitive, psychological, somatic, patient preferences, nutritional status, and social domains. Administration of (seven) patient questionnaires and (ten) professional-administered instruments, by nurse (practitioners), takes estimated 20 and 40 min, respectively. Results are discussed in a multidisciplinary meeting including at least nephrology and geriatric expertise, informing nephrology treatment decisions, and follow-up interventions among which comprehensive geriatric assessment. Conclusion This first multidisciplinary consensus on nephrology-tailored geriatric assessment intent to benefit clinical care and enhance research comparability for older patients with advanced CKD.Key Summary pointsAim To propose a consensus-based geriatric assessment for optimizing both routine care and research in older patients with advanced chronic kidney disease. Findings Using a pragmatic approach, we reached consensus on a suitable nephrology-tailored geriatric assessment to routinely identify major geriatric impairments in older patients with advanced chronic kidney disease. This geriatric assessment contains instruments in functional, cognitive, psychological, somatic, patient preferences, nutritional status, and social domains, and can be administered with patient questionnaires and professional-administered instruments by nurse (practitioners) in approximately 20 and 40 minutes, respectively. Message We propose a consensus test set for standardized nephrology-tailored geriatric assessment, which is currently being implemented in multiple hospitals and studies, to benefit clinical care for older patients with advanced chronic kidney disease and enhance research comparability.Nephrolog

Towards a multisensor station for automated biodiversity monitoring

Rapid changes of the biosphere observed in recent years are caused by both small and large scale drivers, like shifts in temperature, transformations in land-use, or changes in the energy budget of systems. While the latter processes are easily quantifiable, documentation of the loss of biodiversity and community structure is more difficult. Changes in organismal abundance and diversity are barely documented. Censuses of species are usually fragmentary and inferred by often spatially, temporally and ecologically unsatisfactory simple species lists for individual study sites. Thus, detrimental global processes and their drivers often remain unrevealed. A major impediment to monitoring species diversity is the lack of human taxonomic expertise that is implicitly required for large-scale and fine-grained assessments. Another is the large amount of personnel and associated costs needed to cover large scales, or the inaccessibility of remote but nonetheless affected areas. To overcome these limitations we propose a network of Automated Multisensor stations for Monitoring of species Diversity (AMMODs) to pave the way for a new generation of biodiversity assessment centers. This network combines cutting-edge technologies with biodiversity informatics and expert systems that conserve expert knowledge. Each AMMOD station combines autonomous samplers for insects, pollen and spores, audio recorders for vocalizing animals, sensors for volatile organic compounds emitted by plants (pVOCs) and camera traps for mammals and small invertebrates. AMMODs are largely self-containing and have the ability to pre-process data (e.g. for noise filtering) prior to transmission to receiver stations for storage, integration and analyses. Installation on sites that are difficult to access require a sophisticated and challenging system design with optimum balance between power requirements, bandwidth for data transmission, required service, and operation under all environmental conditions for years. An important prerequisite for automated species identification are databases of DNA barcodes, animal sounds, for pVOCs, and images used as training data for automated species identification. AMMOD stations thus become a key component to advance the field of biodiversity monitoring for research and policy by delivering biodiversity data at an unprecedented spatial and temporal resolution. (C) 2022 Published by Elsevier GmbH on behalf of Gesellschaft fur Okologie

Switching iron sucrose to ferric carboxymaltose associates to better control of iron status in hemodialysis patients

Background: Although the efficacy of iron sucrose (IS) and ferric carboxymaltose (FCM) in treating anemia in hemodialysis (HD) patients has been studied individually, a comparison of these two intravenous iron formulations has not yet been performed in HD patients. Methods: We performed a retrospective audit on records of 221 stable HD patients from different HD centers in the Netherlands, who were switched from IS to FCM on a 1: 1 ratio. To assess the effect of the switch on iron status parameters, data from 3 time points before and 3 time points after the switch were analyzed using linear mixed effects models. Subanalyses were done in 2 subgroups of patients anemic or iron deficient at baseline. Results: Hemoglobin increased in all groups (anemic [1.4 g/dL, P <0.001] iron deficient [0.6 g/dL, P <0.001]), while the weekly iron dose was significantly lower when patients received FCM compared to IS (48 vs 55 mg/week, P = 0.04). Furthermore, serum ferritin and transferrin saturation increased in all groups (anemic [64 mu g/L, 5.0%, P <0.001] iron deficient [76 mu g/L, 3.6%, P <0.001]). Finally, the darbepoetin a dose decreased significantly in all groups (anemic [- 16 mu g/wk., P = 0.01] iron deficient [- 11 mu g/wk., P <0.001]). Conclusions: In this real-life study in HD patients, a switch from IS to FCM resulted in an improvement of iron status parameters despite a lower weekly dose of FCM. Furthermore, the ESA dose was reduced during FCM, while hemoglobin levels increased

Calpain inhibition mediates autophagy-dependent protection against polyglutamine toxicity.

Over recent years, accumulated evidence suggests that autophagy induction is protective in animal models of a number of neurodegenerative diseases. Intense research in the field has elucidated different pathways through which autophagy can be upregulated and it is important to establish how modulation of these pathways impacts upon disease progression in vivo and therefore which, if any, may have further therapeutic relevance. In addition, it is important to understand how alterations in these target pathways may affect normal physiology when constitutively modulated over a long time period, as would be required for treatment of neurodegenerative diseases. Here we evaluate the potential protective effect of downregulation of calpains. We demonstrate, in Drosophila, that calpain knockdown protects against the aggregation and toxicity of proteins, like mutant huntingtin, in an autophagy-dependent fashion. Furthermore, we demonstrate that, overexpression of the calpain inhibitor, calpastatin, increases autophagosome levels and is protective in a mouse model of Huntington's disease, improving motor signs and delaying the onset of tremors. Importantly, long-term inhibition of calpains did not result in any overt deleterious phenotypes in mice. Thus, calpain inhibition, or activation of autophagy pathways downstream of calpains, may be suitable therapeutic targets for diseases like Huntington's disease.This is the published version of the manuscript. It is available online from NPG in Cell Death and Differentiaiton here: http://www.nature.com/cdd/journal/vaop/ncurrent/full/cdd2014151a.html

Cholini (Coleoptera: Curculionidae, Molytinae) depositados na Coleção de Invertebrados do Instituto Nacional de Pesquisas da Amazônia

In Brazilian Amazonia, Cholini (Coleoptera, Curculionidae, Molytinae) is represented by 53 species distributed in seven generaAmeris Dejean, 1821; Cholus Germar, 1824; Homalinotus Sahlberg, 1823; Lobaspis Chevrolat, 1881; Odontoderes Sahlberg, 1823; Ozopherus Pascoe, 1872 and Rhinastus Schoenherr, 1825. This work documents the species of Cholini housed in the Invertebrate Collection of the Instituto Nacional de Pesquisas da Amazônia, Manaus, Brazil and gives the geographical and biological data associated with them. A total of 186 Cholini specimens were identified as belonging to 14 species (13 from Brazilian Amazonia) and five genera (Cholus, Homalinotus, Odontoderes, Ozopherus and Rhinastus). Only 24% of the Cholini species reported from Brazilian Amazonia are actually represented in the INPA collection, underscoring the need for a more systematical collecting based on available biological information. The known geographical distribution was expanded for the following speciesCholus granifer (Chevrolat, 1881) for Brazil; C. pantherinus (Olivier, 1790) for Manaus (Amazonas); Cholus parallelogrammus (Germar, 1824) for Piraquara (Paraná); Homalinotus depressus (Linnaeus, 1758) for lago Janauacá (Amazonas) and rio Tocantins (Pará); H. humeralis (Gyllenhal, 1836) for Novo Airão, Coari (Amazonas) and Porto Velho (Rondônia); H. nodipennis (Chevrolat, 1878) for Carauari, Lábrea (Amazonas) and Ariquemes (Rondônia); H. validus (Olivier, 1790) for rio Araguaia (Brasil), Manaus (Amazonas), rio Tocantins (Pará), Porto Velho and BR 364, Km 130 (Rondônia); Odontoderes carinatus (Guérin-Méneville, 1844) for Manaus (Amazonas); O. spinicollis (Boheman, 1836) for rio Uraricoera (Roraima); and Ozopherus muricatus Pascoe, 1872 for lago Janauacá (Amazonas). Homalinotus humeralis is reported for the first time from "urucuri" palm, Attalea phalerata Mart. ex Spreng.Na Amazônia brasileira, Cholini (Coleoptera, Curculionidae, Molytinae) é representada por 53 espécies, distribuídas em sete gêneros: Ameris Dejean, 1821; Cholus Germar, 1824; Homalinotus Sahlberg, 1823; Lobaspis Chevrolat, 1881; Odontoderes Sahlberg, 1823; Ozopherus Pascoe, 1872 e Rhinastus Schoenherr, 1825. Este trabalho documenta as espécies de Cholini depositadas na Coleção de Invertebrados do Instituto Nacional de Pesquisas da Amazônia, Manaus, Brasil, além de apresentar a distribuição geográfica e informações sobre a biologia dessas espécies. Foram identificados 186 espécimes de Cholini, pertencentes a 14 espécies (13 da Amazônia brasileira) e cinco gêneros (Cholus, Homalinotus, Odontoderes, Ozopherus e Rhinastus). Somente 24% das espécies de Cholini registradas para a Amazônia brasileira estão representadas na coleção do INPA, ressaltando a necessidade de um esforço de coleta sistemático baseado na informação biológica disponível. Foi ampliada a distribuição geográfica conhecida das seguintes espécies: Cholus granifer (Chevrolat, 1881) para Brasil; C. pantherinus (Olivier, 1790) para Manaus (Amazonas); Cholus parallelogrammus (Germar, 1824) para Piraquara (Paraná); Homalinotus depressus (Linnaeus, 1758) para lago Janauacá (Amazonas) e rio Tocantins (Pará); H. humeralis (Gyllenhal, 1836) para Novo Airão, Coari (Amazonas) e Porto Velho (Rondônia); H. nodipennis (Chevrolat, 1878) para Carauari, Lábrea (Amazonas) e Ariquemes (Rondônia); H. validus (Olivier, 1790) para rio Araguaia (Brasil), Manaus (Amazonas), rio Tocantins (Pará), Porto Velho e BR 364, Km 130 (Rondônia); Odontoderes carinatus (Guérin-Méneville, 1844) para Manaus (Amazonas); O. spinicollis (Boheman, 1836) para rio Uraricoera (Roraima) e Ozopherus muricatus Pascoe, 1872 para lago Janauacá (Amazonas). Homalinotus humeralis é associado pela primeira vez com a palmeira urucuri Attalea phalerata Mart. ex Spreng