Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Waning Humoral Response 3 to 6 Months after Vaccination with the SARS-COV-2 BNT162b2 mRNA Vaccine in Dialysis Patients

Background and objectives: The short-term reported antibody response to SARS-COV-2 vaccination in dialysis patients is high, with a seroconversion response rate up to 97%. Data on the long-term durability of this response are scarce. Our objective was to characterize the long-term anti-spike antibody level in dialysis patients. Design, setting, participants, and measurements: In an observational study, we measured SARS-COV-2 anti-spike antibody levels in dialysis patients who completed 2 doses of the BNT162b2 mRNA SAR S-COV-2 vaccine at 1, 3 and 6 months after the second vaccine dose. We compared the response to dialysis patients who were infected with COVD-19 and to a control group of healthcare-employees. Results: One hundred and forty-two dialysis patients who had been vaccinated (ages 64 &plusmn; 11.9 years, 61% male), 33 dialysis patients who had COVID-19 infection (ages 54 &plusmn; 14.3 years, 55% male) and 104 individuals in the control group (ages 50 &plusmn; 12.2 years, 44% male) were included. The response rate in the vaccinated dialysis patients was 94%, 78% and 73% at 1, 3 and 6 months after the second vaccine dose. In the COVID-19 infected dialysis group and in the control group, the response rate remained at 100% over 6 months. The percentage of change in antibody levels between one and 6 months was &minus;66% in the vaccinated dialysis group, &minus;28% in the control group (p &lt; 0.001) and +48% in dialysis patients who had been infected with COVID-19 (p &lt; 0.001). A non-responder status at 6 months was associated with a lower albumin level. No serious adverse events following vaccination were reported. In conclusion: the initially high response rate to the BNT162b2 vaccine in dialysis patients decreases rapidly. Our results indicate that an early booster (3rd) dose, at three months after the second dose, may be advised for this population to preserve the humoral immunity

The Relationship among the Inspiratory Muscle Strength, the Perception of Dyspnea and Inhaled Beta2-Agonists in Patients with Asthma

BACKGROUND: It is well documented that the perception of dyspnea (POD), subjectively reported by patients, is related to the activity and strength of the inspiratory muscles, and influences the use of 'as needed' beta2-agonists

Exocytotic and endocytotic proteins exhibit different domain architectures

Molecular architecture of exocytotic and endocytotic proteins (15 representatives each; top and bottom frames, respectively). The complete lists and additional structural information is accessible in Additional data file 8. The proteins are drawn to scale, and the domain architectures are based on Pfam protein family. Domains are indicated by their colors. Detailed information on the properties of the domains is available in Additional data file 2 [part b].<p><b>Copyright information:</b></p><p>Taken from "Evolution of insect proteomes: insights into synapse organization and synaptic vesicle life cycle"</p><p>http://genomebiology.com/2008/9/2/R27</p><p>Genome Biology 2008;9(2):R27-R27.</p><p>Published online 7 Feb 2008</p><p>PMCID:PMC2374702.</p><p></p

Presynaptic proteins participate in interconnected protein-protein graphs

The protein-interacting graphs are extracted from STRING tool and supported by the literature, experimental data, and strong homology inference. Only high confidence interactions are shown (see Materials and methods). The central protein in each graph (marked with a red frame) is a representative for synaptojanin 1 (SYNJ1; a key signaling protein in endocytosis), NRXN1 (in presynaptic membrane interaction and synaptogenesis), ERC2 (an active zone organizer), RIMS (a genuine component of the active zone), and vehicle-associated membrane protein (VAMP)8 (a component of the exocytosis). Protein names are according to the official gene symbols (as in Table 1 and Additional data file 2). Protein valences (the number of direct edges from the vertex) are marked in parenthesis. Note that the graphs for RIMS, ERC2, and NRXN1 are of a relatively low connectivity. Protein vertices are colored according to the conservation index; proteins with a sequence similarity above 65% relative to a human homolog are framed in black, otherwise they are marked in light blue. Proteins that were missing in one or more of the insect representatives are framed in orange. Proteins that do not have insect homologs (as in Table 1 and Additional data file 2) are marked by a yellow circle. A quantitative measure for the density of protein-protein interactions in the graph is added as well as the network conservation score (Con).<p><b>Copyright information:</b></p><p>Taken from "Evolution of insect proteomes: insights into synapse organization and synaptic vesicle life cycle"</p><p>http://genomebiology.com/2008/9/2/R27</p><p>Genome Biology 2008;9(2):R27-R27.</p><p>Published online 7 Feb 2008</p><p>PMCID:PMC2374702.</p><p></p

Valence of proteins in the interaction graphs and sequence conservation levels are positively correlated

Genes from the presynaptic 120 genes (PS120) list were measured for their sequence conservation (percentage sequence identity between insects and human) and for the valance of each protein. The number of proteins for each sequence identity range is indicated in parenthesis. The number of protein partners for each PS120 is provided in Additional data file 5. Note that a positive correlation between the protein conservation index and the protein valance is evident only at highly conserved sequences (>50% identity). Data from protein complexes (coatomer protein [COP]-1 and peroxin biogenesis [PEX]) follow a similar trend as the PS120. Proteins of each complex were divided into groups according to their sequence identity level (low [L], medium [M], and high [H]). The number of proteins in each group is indicated in parenthesis. PEX (16 proteins, including the 14 core PEX proteins; Figure 4) are weakly conserved between human and insects, while COP-1 (nine proteins; Figure 3a) exhibit a stronger conservation index. Note that the PEX and COP-1 proteins are not included in the PS120 set.<p><b>Copyright information:</b></p><p>Taken from "Evolution of insect proteomes: insights into synapse organization and synaptic vesicle life cycle"</p><p>http://genomebiology.com/2008/9/2/R27</p><p>Genome Biology 2008;9(2):R27-R27.</p><p>Published online 7 Feb 2008</p><p>PMCID:PMC2374702.</p><p></p