Maher Holm (crookrefund7)

Acute heart failure is a life-threatening clinical condition. Levosimendan is an effective inotropic agent used to maintain cardiac output, but its usage is limited by the lack of evidence in patients with severely abnormal renal function. Therefore, we analyzed data of patients with acute heart failure with and without abnormal renal function to examine the effects of levosimendan. We performed this retrospective cohort study using data from the Chang Gung Research Database (CGRD) of Chang Gung Memorial Hospital (CGMH). Patients admitted for heart failure with LVEF ≤ 40% between January 2013 and December 2018 who received levosimendan or dobutamine in the critical cardiac care units (CCU) were identified. Patients with extracorporeal membrane oxygenation (ECMO) were excluded. Outcomes of interest were mortality at 30, 90, and 180days after the cohort entry date. There were no significant differences in mortality rate at 30, 90, and 180days after the cohort entry date between the levosimendan and dobutamine groups, or between subgroups of patients with an estimated glomerular filtration rate (eGFR) ≥ 30mL/min/1.73 m and eGFR < 30mL/min/1.73 m or on dialysis. The results were consistent before and after propensity score matching. Levosimendan did not increase short- or long-term mortality rates in critical patients with acute heart failure and reduced ejection fraction compared to dobutamine, regardless of their renal function. An eGFR less than 30mL/min/1.73 m was not necessarily considered a contraindication for levosimendan in these patients. Levosimendan did not increase short- or long-term mortality rates in critical patients with acute heart failure and reduced ejection fraction compared to dobutamine, regardless of their renal function. An eGFR less than 30 mL/min/1.73 m2 was not necessarily considered a contraindication for levosimendan in these patients.One way to understand ductal adenocarcinoma of the pancreas (pancreatic cancer) is to view it as unimaginably large numbers of evolving living organisms interacting with their environment. This "evolutionary view" creates both expected and surprising perspectives in all stages of neoplastic progression. Advances in the field will require greater attention to this critical evolutionary prospective.COP9 signalosome (CSN) is a nuclear complex composed of eight distinct subunits that governs vast developmental processes in Arabidopsis thaliana (L.) Heynh. The null alleles of csn mutants display pleiotropic phenotypes that result in seedling lethality. To date, several partially complemented transgenic plants, expressing the particular CSN subunit in its corresponding null mutant allele, were utilized to bypass seedling lethality and investigate CSN regulation at later stages of development. Pamiparib One such transgenic plant corresponding to CSN1 subunit, fus6/CSN1-3-4, accumulates wild-type level of CSN1 and displays normal plant architecture at vegetative stage. Here we show through histological analyses that fus6/CSN1-3-4 plants display impairment of pollen development at the bicellular stage. This defect is identical to that observed in RNAi plants of SAP130, encoding a subunit of the multiprotein splicing factor SF3b. We further dissected the previously reported interaction between CSN1 and SAP130, to reveal that approximately 100 amino-acid residues located at the N-terminal end of CSN1 (CSN1NN) were essential for this interaction. In silico structure modeling demonstrated that CSN1NN could swing out towards SAP130 to dock onto its Helical Insertion protruding from the structure. These results support our model that CSN1 embeds itself within CSN protein complex through its C-terminal half and reaches out to targets through its N-terminal portion of the protein. Taken together, this is the first report to document the identical loss-of-function phenotypes of CSN1 and SAP130 during male gametogenesis. Th