Optimizing the timing of nephrology referral for patients with diabetic kidney disease

Diabetis mellitus; Malaltia renal diabètica; Atenció multidisciplinàriaDiabetes mellitus; Diabetic kidney disease; Multidisciplinary careDiabetes mellitus; Enfermedad renal diabética; Atención multidisciplinariaAge-standardized rates of diabetes mellitus (DM)-related complications, such as acute myocardial infarction, stroke or amputations, have decreased in recent years, but this was not associated with a clear reduction of the incidence of advanced chronic kidney disease (CKD) requiring renal replacement therapy. The early detection of diabetic kidney disease (DKD) is a key to reduce complications, morbidity and mortality. Consensus documents and clinical practice guidelines recommend referral of DM patients to nephrology when the estimated glomerular filtration rate falls below 30 mL/min/1.73 m2 or when albuminuria exceeds 300 mg/g urinary creatinine. Conceptually, it strikes as odd that patients with CKD are referred to the specialist caring for the prevention and treatment of CKD only when >70% of the functioning kidney mass has been lost. The increasing global health burden of CKD, driven in large part by DKD, the suboptimal impact of routine care on DKD outcomes as compared with other DM complications, the realization that successful therapy of CKD requires early diagnosis and intervention, the advances in earlier diagnosis of kidney injury and the recent availability of antidiabetic drugs with a renal mechanism of action and lack of hypoglycaemia risk, which additionally are cardio- and nephroprotective, all point towards a paradigm shift in the care for DM patients in which they should be referred earlier to nephrology as part of a coordinated and integrated care approach.Sources of support: FIS/Fondos FEDER PI18/01386, PI19/00588, PI19/00815, DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM

Exploring Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors for Organ Protection in COVID-19

Hospital admissions and mortality from the Coronavirus disease 2019 (COVID-19) pandemic are spreading throughout the world, and second and third waves are thought to be likely. Risk factors for severe COVID-19 include diabetes, chronic kidney disease and cardiovascular disease. Currently, there is no vaccine and no approved therapy. Therapeutic approaches are aimed at preventing viral replication and spread, limiting the impact of the inflammatory overdrive (cytokine storm), preventing thromboembolic complications and replacing or supporting organ function. However, despite organ support, mortality is currently 65% for those receiving advanced respiratory support and 78% for those requiring renal replacement therapies. Thus, efforts should be made to provide adjuvant organ protection therapy. This may imply novel therapies in clinical development (e.g., the Fas ligand trap asunercept), but uptake of repurposed drugs already in clinical use may be faster. In this regard, sodium glucose co-transporter-2 (SGLT2) inhibitors were recently shown to protect the heart and kidney both within and outside of a diabetic milieu context. Further, preclinical data support a beneficial effect for the lung. We now discuss the potential benefits and risks of SGLT2 inhibitors in COVID-19 and an ongoing clinical trial testing the impact of dapagliflozin on outcomes in COVID-19 patients with respiratory failure

Prevalence and influence of cys407* Grm2 mutation in Hannover-derived Wistar rats:mGlu2 receptor loss links to alcohol intake, risk taking and emotional behaviour

AbstractModulation of metabotropic glutamate 2 (mGlu2) receptor function has huge potential for treating psychiatric and neurological diseases. Development of drugs acting on mGlu2 receptors depends on the development and use of translatable animal models of disease. We report here a stop codon mutation at cysteine 407 in Grm2 (cys407*) that is common in some Wistar rats. Therefore, researchers in this field need to be aware of strains with this mutation. Our genotypic survey found widespread prevalence of the mutation in commercial Wistar strains, particularly those known as Han Wistar. Such Han Wistar rats are ideal for research into the separate roles of mGlu2 and mGlu3 receptors in CNS function. Previous investigations, unknowingly using such mGlu2 receptor-lacking rats, provide insights into the role of mGlu2 receptors in behaviour. The Grm2 mutant rats, which dominate some selectively bred lines, display characteristics of altered emotionality, impulsivity and risk-related behaviours and increased voluntary alcohol intake compared with their mGlu2 receptor-competent counterparts. In addition, the data further emphasize the potential therapeutic role of mGlu2 receptors in psychiatric and neurological disease, and indicate novel methods of studying the role of mGlu2 and mGlu3 receptors

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Acute Relaxation Response Induced by Tibetan Singing Bowl Sounds: A Randomized Controlled Trial

The prevalence of anxiety has increased dramatically due to COVID-19, so effective preventive interventions are welcome. The main objective of our study was to compare the acute relaxation response (RR) induced by Tibetan singing bowl (TSB) sound-based treatment against progressive muscle relaxation (PMR) and a control waiting list group (CWL) in a single treatment session in an adult nonclinical anxious population. In this cross-sectional randomized control trial, 50 participants selected based on high state anxiety were randomly assigned to one of the experimental groups. Pre/post self-reported anxiety, electroencephalographic activity (EEG), and heart rate variability (HRV) were recorded at baseline (T1), minute 15 (T2), minute 30 (T3), and minute 45 (T4). The TSB group showed significant reductions in alpha power (from T2 to T4) and increased HRV (from T3 to T4) compared with the PMR and CWL groups. Moreover, TSB and PMR both showed significant reductions in self-reported anxiety compared with CWL, with this effect being more evident in the TSB group. We concluded that a single session of TSB treatment was able to induce a more evident psychological/physiological relaxation response compared with PMR and CWL. TSB could be a relevant acute intervention in stressful situations or crisis intervention and while waiting for conventional interventions

A maturational shift in the frontal cortex synaptic transcriptional landscape underlies schizophrenia-relevant behavioural traits:A congenital rat model

Disruption of brain development early in life may underlie the neurobiology behind schizophrenia. We have reported more immature synaptic spines in the frontal cortex (FC) of adult Roman High-Avoidance (RHA-I) rats, a behavioural model displaying schizophrenia-like traits. Here, we performed a whole transcriptome analysis in the FC of 4 months old male RHA-I (n=8) and its counterpart, the Roman Low-Avoidance (RLA-I) (n=8). We identified 203 significant genes with overrepresentation of genes involved in synaptic function. Next, we performed a gene set enrichment analysis (GSEA) for genes co-expressed during neurodevelopment. Gene networks were obtained by weighted gene co-expression network analysis (WGCNA) of a transcriptomic dataset containing human FC during lifespan (n=269). Out of thirty-one functional gene networks, six were significantly enriched in the RHA-I. These were differentially regulated during infancy and enriched in biological ontologies related to myelination, synaptic function, and immune response. We validated differential gene expression in a new cohort of adolescent (&lt;=2 months old) and young-adult (&gt;=3 months old) RHA-I and RLA-I rats. The results confirmed overexpression of Gsn, Nt5cd1, Ppp1r1b, and Slc9a3r1 in young-adult RHA-I, while Cables1, a regulator of Cdk5 phosphorylation in actin regulation and involved in synaptic plasticity and maturation, was significantly downregulated in adolescent RHA-I. This age-related expression change was also observed for presynaptic components Snap25 and Snap29. Our results show a different maturational expression profile of synaptic components in the RHA-I strain, supporting a shift in FC maturation underlying schizophrenia-like behavioural traits and adding construct validity to this strain as a neurodevelopmental model.</p

Arquivologia, biblioteconomia e ciência da informação: identidades, contrastes e perspectivas de interlocução

Esta coletânea reúne a maioria das conferências e palestras proferidas no 2º Seminário de Estudos da Informação, realizado de 26 a 28 de setembro de 2011, pelo Programa de Pós-Graduação em Ciência da Informação – Mestrado da Universidade Federal Fluminense. A obra se propõe a consolidar a iniciativa inaugurada em 2009, com a primeira edição do seminário, continuando a oferecer ao leitor um espaço de reflexão e crítica sobre temas relevantes para os profissionais das áreas de arquivologia, biblioteconomia e ciência da informação

Computing Activities at the Spanish Tier-1 and Tier-2s for the ATLAS experiment in the LHC Run3 period and towards High Luminosity (HL-LHC)

The ATLAS Spanish Tier-1 and Tier-2s have more than 18 years of experience in the deployment and development of LHC computing components and their successful operations. The sites are actively participating in, and even coordinating, R&D computing activities in the LHC Run3 and developing the computing models needed in HL-LHC period. In this contribution, we present details on the integration of some components, such as HPC computing resources to execute ATLAS simulation workflows; the development of new techniques to improve efficiency in a cost-effective way; and improvements in Data Organization, Management and Access through storage consolidations, the use of data Caches, and improving experiment data catalogues, like Event Index. The design and deployment of novel analysis facilities using GPUs together with CPUs and techniques like Machine Learning will also be presented. ATLAS Tier-1 and Tier-2 sites in Spain are, and will be, contributing to significant R&D in computing, evaluating different models for improving performance of computing and data storage capacity in the LHC High Luminosity era

Computing Activities at the Spanish Tier-1 and Tier-2s for the ATLAS experiment in the LHC Run3 period and towards High Luminosity (HL-LHC)

The ATLAS Spanish Tier-1 and Tier-2s have more than 18 years of experience in the deployment and development of LHC computing components and their successful operation. The sites are actively participating in, and even coordinating, R&D computing activities in the LHC Run3 and developing the computing models needed in the HL-LHC period. In this contribution, we present details on the integration of some components, such as HPC computing resources to execute ATLAS simulation workflows; the development of new techniques to improve efficiency in a cost-effective way; and improvements in Data Organization, Management and Access through storage consolidations, the use of data Caches, and improving experiment data catalogues, through contributions such as Event Index. The design and deployment of novel analysis facilities using GPUs together with CPUs and techniques like Machine Learning will also be presented. ATLAS Tier-1 and Tier-2 sites in Spain, are, and will be, contributing to significant R&D in computing and evaluating different models for improving performance of computing and data storage capacity in the LHC High Luminosity era