Benefit of cardiac rehabilitation in acute heart failure patients with cognitive impairment.

Aims: This study aimed to evaluate the prevalence of cognitive impairment among patients with acute heart failure (AHF), its prognosis, and the effects of cardiac rehabilitation (CR) on these patients' outcomes. Methods: Overall, 247 consecutive AHF patients (median age, 60 years; males, 78.5 %) were evaluated from March 2015 to May 2021. Patients received an AHF disease management program coordinated by an HF specialist nurse and underwent a Luria-Nebraska Neuropsychological battery-screening test (LNNB-S) assessment during admission. Cognitive impairment was defined as an LNNB-S score ≥10. Patients who underwent at least one session of phase II CR and continued with the home-based exercise program were considered to have received CR. The primary endpoint was composite all-cause mortality or readmission after a 3.30-year follow-up (interquartile range, 1.69-5.09 years). Results: Cognitive impairment occurred in 53.0 % and was associated with significantly higher composite endpoint, all-cause mortality, and readmission rates (p=<0.001, 0.001, and 0.015, respectively). In the total cohort, 40.9 % of patients experienced the composite endpoint. Multivariate analysis showed that the peak VO2 was a significant predictor of the composite endpoint. After adjustment, CR significantly decreased the event rate of the composite endpoint and the all-cause mortality in patients with cognitive impairment (log-rank p = 0.024 and 0.009, respectively). However, CR did not have a significant benefit on the composite endpoint and the all-cause mortality in patients without cognitive impairment (log-rank p = 0.682 and 0.701, respectively). Conclusion: Cognitive impairment is common in AHF patients and can lead to poor outcomes. CR is a standard treatment to improve prognosis.

Stereodivergent, Kinetically Controlled Isomerization of Terminal Alkenes via Nickel Catalysis.

Because internal alkenes are more challenging synthetic targets than terminal alkenes, metal-catalyzed olefin mono-transposition (i.e., positional isomerization) approaches have emerged to afford valuable E- or Z- internal alkenes from their complementary terminal alkene feedstocks. However, the applicability of these methods has been hampered by lack of generality, commercial availability of precatalysts, and scalability. Here, we report a nickel-catalyzed platform for the stereodivergent E/Z-selective synthesis of internal alkenes at room temperature. Commercial reagents enable this one-carbon transposition of terminal alkenes to valuable E- or Z-internal alkenes via a Ni-H-mediated insertion/elimination mechanism. Though the mechanistic regime is the same in both systems, the underlying pathways that lead to each of the active catalysts are distinct, with the Z-selective catalyst forming from comproportionation of an oxidative addition complex followed by oxidative addition with substrate and the E-selective catalyst forming from protonation of the metal by the trialkylphosphonium salt additive. In each case, ligand sterics and denticity control stereochemistry and prevent over-isomerization.

Pregnane X receptor activation alleviates renal fibrosis in mice via interacting with p53 and inhibiting the Wnt7a/ß-catenin signaling.

Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) with various etiologies, which seriously affects the structure and function of the kidney. Pregnane X receptor (PXR) is a member of the nuclear receptor superfamily and plays a critical role in regulating the genes related to xenobiotic and endobiotic metabolism in mammals. Previous studies show that PXR is expressed in the kidney and has protective effect against acute kidney injury (AKI). In this study, we investigated the role of PXR in CKD. Adenine diet-induced CKD (AD) model was established in wild-type and PXR humanized (hPXR) mice, respectively, which were treated with pregnenolone-16α-carbonitrile (PCN, 50 mg/kg, twice a week for 4 weeks) or rifampicin (RIF, 10 mg·kg-1·d-1, for 4 weeks). We showed that both PCN and RIF, which activated mouse and human PXR, respectively, improved renal function and attenuated renal fibrosis in the two types of AD mice. In addition, PCN treatment also alleviated renal fibrosis in unilateral ureter obstruction (UUO) mice. On the contrary, PXR gene deficiency exacerbated renal dysfunction and fibrosis in both adenine- and UUO-induced CKD mice. We found that PCN treatment suppressed the expression of the profibrotic Wnt7a and ß-catenin in AD mice and in cultured mouse renal tubular epithelial cells treated with TGFß1 in vitro. We demonstrated that PXR was colocalized and interacted with p53 in the nuclei of tubular epithelial cells. Overexpression of p53 increased the expression of Wnt7a, ß-catenin and its downstream gene fibronectin. We further revealed that p53 bound to the promoter of Wnt7a gene to increase its transcription and ß-catenin activation, leading to increased expression of the downstream profibrotic genes, which was inhibited by PXR. Taken together, PXR activation alleviates renal fibrosis in mice via interacting with p53 and inhibiting the Wnt7a/ß-catenin signaling pathway.

Alien species revises systematic status: integrative species delimitation of two similar taxa of Symbrenthia Hübner, [1819] (Lepidoptera, Nymphalidae).

Introduction of organisms to new range may impose detrimental effects on local organisms, especially when closely related species are involved. Species delimitation employing an integrative taxonomy approach may provide a quick assessment for the species status between taxa of interest, and to infer ecological competition and/or introgression that may be associated with the introduction. A nymphalid butterfly, Symbrenthia lilaea lunica, was recently introduced to Taiwan, where a closely related local taxon, S. l. formosanus, can be found. We employed multiple species delimitation methods to study the species status between the two taxa, and the results revealed that they can be recognized as two distinct species, revised to S. l. lilaea (syn. nov.) and S. formosanus (stat. rev.) respectively. We further performed a niche modeling approach to investigate the ecological interaction between the two species. The taxonomic status of the two taxa, now elevated to species, has been revised and conservation facing rapid expansion of the introduced species discussed.

Prognostic value of serum sodium variability within 72 hours and lactic acid combined with severity score in patients with sepsis / 中华危重病急救医学

OBJECTIVE@#To explore the predictive value of serum sodium variability within 72 hours, lactic acid (Lac), sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) in predicting the 28-day prognosis of sepsis patients.@*METHODS@#The clinical data of patients with sepsis admitted to the department of intensive care unit (ICU) of the Affiliated Qingdao Municipal Hospital of Qingdao University from December 2020 to December 2021 were retrospectively analyzed, including age, gender, previous medical history, temperature, heart rate, respiratory rate, systolic pressure, diastolic pressure, white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), C-reactive protein (CRP), pH value, arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), Lac, prothrombin time (PT), activated partial thromboplastin time (APTT), serum creatinine (SCr), total bilirubin (TBil), albumin (Alb), SOFA, APACHE II score, and 28-day prognosis. Multivariate Logistic regression was used to analyze the risk factors of death in sepsis patients. Receiver operator characteristic curve (ROC curve) was used to analyze the predictive value of serum sodium variability within 72 hours, Lac, SOFA, APACHE II alone and in combination on the prognosis of patients with sepsis.@*RESULTS@#A total of 135 patients with sepsis were included, 73 survived and 62 died at 28 days, with 28-day mortality of 45.93%. (1) Compared with the survival group, SOFA, APACHE II, Lac and serum sodium variability within 72 hours in the death group were significantly higher [SOFA: 10.00 (8.00, 12.00) vs. 6.00 (5.00, 8.00), APACHE II: 18.00 (16.00, 21.25) vs. 13.00 (11.00, 15.00), Lac (mmol/L): 3.55 (2.90, 4.60) vs. 2.00 (1.30, 2.80), serum sodium variability within 72 hours: 3.4% (2.6%, 4.2%) vs. 1.4% (1.1%, 2.5%)], the differences were statistically significant (all P < 0.01). (2) Multivariate Logistic regression showed that SOFA, APACHE II, Lac, serum sodium variability within 72 hours were independent risk factors of prognosis in patients with sepsis [SOFA: odds ratio (OR) = 1.479, 95% confidence interval (95%CI) was 1.114-1.963, P = 0.007; APACHE II: OR = 1.163, 95%CI was 1.009-1.340, P = 0.037; Lac: OR = 1.387, 95%CI was 1.014-1.896, P = 0.040; serum sodium variability within 72 hours: OR = 1.634, 95%CI was 1.102-2.423, P = 0.015]. (3) ROC curve analysis showed that SOFA, APACHE II, Lac and serum sodium variability within 72 hours had certain predictive value for the prognosis of sepsis patients [SOFA: the area under the ROC curve (AUC) = 0.858, 95%CI was 0.795-0.920, P = 0.000; APACHE II: AUC = 0.845, 95%CI was 0.776-0.913, P = 0.000; Lac: AUC = 0.840, 95%CI was 0.770-0.909, P = 0.000; serum sodium variability within 72 hours: AUC = 0.842, 95%CI was 0.774-0.910, P = 0.000]. The combined predictive value of the four indicators (AUC = 0.917, 95%CI was 0.870-0.965, P = 0.000) was higher than that of any single indicator, and has higher specificity (79.5%) and sensitivity (93.5%), indicating that the combined index has higher predictive value for the prognosis of sepsis patients than any single index.@*CONCLUSIONS@#SOFA, APACHE II, Lac, serum sodium variability within 72 hours are independent risk factors for 28-day death in patients with sepsis. The combination of SOFA score, APACHE II score, Lac and serum sodium variability within 72 hours has higher predictive value for prognosis than single index.

A subset of Memory B-derived antibody repertoire from 3-dose vaccinees is ultrapotent against diverse and highly transmissible SARS-CoV-2 variants, including Omicron

Omicron, the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. We examined whether sera from individuals who received two or three doses of inactivated vaccine, could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2/60) and 95% (57/60) for 2- and 3-dose vaccinees, respectively. For three-dose recipients, the geometric mean neutralization antibody titer (GMT) of Omicron was 15, 16.5-fold lower than that of the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in 3-dose vaccinees, half of which recognize the receptor binding domain (RBD) and show that a subset of them (24/163) neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron, potently. Therapeutic treatments with representative broadly neutralizing mAbs individually or antibody cocktails were highly protective against SARS-CoV-2 Beta infection in mice. Atomic structures of the Omicron S in complex with three types of all five VOC-reactive antibodies defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to one major class of antibodies bound at the right shoulder of RBD through altering local conformation at the binding interface. Our results rationalize the use of 3-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are a rational target for a universal sarbecovirus vaccine. One sentence summaryA sub-set of antibodies derived from memory B cells of volunteers vaccinated with 3 doses of an inactivated SARS-CoV-2 vaccine work individually as well as synergistically to keep variants, including Omicron, at bay.

Feature and impact of guideline-directed medication prescriptions for heart failure with reduced ejection fraction accompanied by chronic kidney disease.

Background: With respect to total mortality and cardiovascular mortality, the feature and impact of guideline-directed medication (GDM) prescriptions for heart failure with reduced ejection fraction (HFrEF) with chronic kidney disease (CKD) are unknown. Therefore, we aimed to determine these aspects. Methods: GDM prescriptions and their impact on discharged patients with and without CKD were analyzed. To analyze differences in one-year clinical outcomes, propensity score matching was conducted on a cohort of patients with concomitant HFrEF and CKD who received more and fewer GDM prescriptions. Results: A total of 1509 patients were enrolled in Taiwan's HFrEF registry from May 2013 to October 2014, and 1275 discharged patients with complete one-year follow-up were further analyzed. Of these patients, 468 (36.7%) had moderate CKD, whereas 249 (19.5%) had advanced CKD. Patients with advanced CKD received fewer prescribed GDMs than other patients. Multivariate analysis revealed that peripheral arterial occlusive disease, thyroid disorder, advanced HF at discharge, diastolic blood pressure, digoxin use, and fewer prescribed GDMs were independent predictors of one-year total mortality. After propensity score matching, patients with fewer prescribed GDMs had higher one-year total mortality rate than those with more prescribed GDMs (P=0.036). Conclusions: CKD at discharge from HF hospitalization was associated with fewer GDM prescriptions, particularly in patients with more advanced CKD. The propensity-matched analysis indicated that more GDM prescriptions led to better clinical outcomes in HFrEF patients with CKD. Careful interpretation of changes in renal function during HF hospitalization may improve GDM prescriptions.

Correction: Melatonin attenuated the brain damage and cognitive impairment partially through MT2 melatonin receptor in mice with chronic cerebral hypoperfusion.

[This corrects the article DOI: 10.18632/oncotarget.20382.].

The Interrelationship between Ventilatory Inefficiency and Left Ventricular Ejection Fraction in Terms of Cardiovascular Outcomes in Heart Failure Outpatients.

The relationship between left ventricular ejection fraction (LVEF) and cardiovascular (CV) outcome is documented in patients with low LVEF. Ventilatory inefficiency is an important prognostic predictor. We hypothesized that the presence of ventilatory inefficiency influences the prognostic predictability of LVEF in heart failure (HF) outpatients. In total, 169 HF outpatients underwent the cardiopulmonary exercise test (CPET) and were followed up for a median of 9.25 years. Subjects were divided into five groups of similar size according to baseline LVEF (≤39%, 40-58%, 59-68%, 69-74%, and ≥75%). The primary endpoints were CV mortality and first HF hospitalization. The Cox proportional hazard model was used for simple and multiple regression analyses to evaluate the interrelationship between LVEF and ventilatory inefficiency (ventilatory equivalent for carbon dioxide (VE/VCO2) at anaerobic threshold (AT) >34.3, optimized cut-point). Only LVEF and VE/VCO2 at AT were significant predictors of major CV events. The lower LVEF subgroup (LVEF ≤ 39%) was associated with an increased risk of CV events, relative to the LVEF ≥75% subgroup, except for patients with ventilatory inefficiency (p = 0.400). In conclusion, ventilatory inefficiency influenced the prognostic predictability of LVEF in reduced LVEF outpatients. Ventilatory inefficiency can be used as a therapeutic target in HF management.

Immature stages of Neptis reducta Fruhstorfer, 1908 (Lepidoptera, Nymphalidae, Neptini): morphology, ecology and food specialty.

Neptis reducta Fruhsorfer, 1908 is currently recognized as a nymphalid butterfly found only in Taiwan and Thailand, with previously recorded larval hostplant and immature biology involving mis-identifications. The present study recognizes Aphananthe aspera (Cannabaceae) as the sole larval hostplant for N. reducta, and the nymphalid butterfly is the first known lepidopterous insect specialized on Aphananthe.

On revised systematic status of Mycalesis suaveolens kagina Fruhstorfer, 1911, with notes on its immature biology and hostplant associations.

Mycalesis kagina Fruhstorfer, 1911 is separated from Mycalesis suaveolens Wood-Mason de Nicéville, 1883 to represent a species endemic to Taiwan based upon COI barcode divergence, morphological diagnosis of larva, and genitalia of both sexes. Both kagina and suaveolens are confirmed as members of the genus Mycalesis in Mycalesina. Immature morphology, biology, and hostplant associations for both species are given for the first time. Larvae of both species are recognized as specialists on Zingiberaceae, a plant family rarely used by satyrid butterflies.

Impact of multi-disciplinary treatment strategy on systolic heart failure outcome.

BACKGROUND: Patients with reduced ejection fraction have high rates of mortality and readmission after hospitalization for heart failure. In Taiwan, heart failure disease management programs (HFDMPs) have proven effective for reducing readmissions for decompensated heart failure or other cardiovascular causes by up to 30%. However, the benefits of HFDMP in different populations of heart failure patients is unknown. METHOD: This observational cohort study compared mortality and readmission in heart failure patients who participated in an HFDMP (HFDMP group) and heart failure patients who received standard care (non-HFDMP group) over a 1-year follow-up period after discharge (December 2014 retrospectively registered). The components of the intervention program included a patient education program delivered by the lead nurse of the HFDMP; a cardiac rehabilitation program provided by a physical therapist; consultation with a dietician, and consultation and assessment by a psychologist. The patients were followed up for at least 1 year after discharge or until death. Patient characteristics and clinical demographic data were compared between the two groups. Cox proportional hazards regression analysis was performed to calculate hazard ratios (HRs) for death or recurrent events of hospitalization in the HFDMP group in comparison with the non-HFDMP group while controlling for covariates. RESULTS: The two groups did not significantly differ in demographic characteristics. The risk of readmission was lower in the HFDMP group, but the difference was not statistically significant (HR = 0.36, p = 0.09). In patients with ischemic cardiomyopathy, the risk of readmission was significantly lower in the HFDMP group compared to the non-HFDMP group (HR = 0.13, p = 0.026). The total mortality rate did not have significant difference between this two groups. CONCLUSION: The HFDMP may be beneficial for reducing recurrent events of heart failure hospitalization, especially in patients with ischemic cardiomyopathy. TRIAL REGISTRATION: Longitudinal case-control study ISRCTN98483065 , 24/09/2019, retrospectively registered.

Calcitriol Attenuates Doxorubicin-Induced Cardiac Dysfunction and Inhibits Endothelial-to-Mesenchymal Transition in Mice.

Doxorubicin (Dox) is an effective anti-neoplasm drug, but its cardiac toxicity limits its clinical use. Endothelial-to-mesenchymal transition (EndMT) has been found to be involved in the process of heart failure. It is unclear whether EndMT contributes to Dox-induced cardiomyopathy (DoIC). Calcitriol, an active form Vitamin D3, blocks the growth of cancer cells by inhibiting the Smad pathway. To investigate the effect of calcitriol via inhibiting EndMT in DoIC, C57BL/6 mice and endothelial-specific labeled mice were intraperitoneally administered Dox twice weekly for 4 weeks (32 mg/kg cumulative dose) and were subsequently treated with or without calcitriol for 12 weeks. Echocardiography revealed diastolic dysfunction at 13 weeks following the first Dox treatment, accompanied by increased myocardial fibrosis and up-regulated pro-fibrotic proteins. Calcitriol attenuated Dox-induced myocardial fibrosis, down-regulated pro-fibrotic proteins and improved diastolic function. Endothelial fate tracing revealed that EndMT-derived cells contributed to Dox-induced cardiac fibrosis. In vitro, human umbilical vein endothelial cells and mouse cardiac fibroblasts were treated with Transforming growth factor (TGF)-ß with or without calcitriol. Morphological, immunofluorescence staining, and Western blot analyses revealed that TGF-ß-induced EndMT and fibroblast-to-myofibroblast transition (FMT) were attenuated by calcitriol by the inhibition of the Smad2 pathway. Collectively, calcitriol attenuated DoIC through the inhibition of the EndMT and FMT processes.

Diabetes Mellitus: An Independent Risk Factor of In-Hospital Mortality in Patients with Infective Endocarditis in a New Era of Clinical Practice.

Infective endocarditis (IE) is a severe disease with a hospital mortality rate of 17%-25%. Early identification of IE patients with high risk of mortality may improve their clinical outcomes. Patients with diabetes mellitus (DM) who develop infective diseases are associated with worse outcomes. This study aimed to define the impact of DM on long-term mortality in IE patients. A total of 412 patients with definite IE from February 1999 to June 2012 were enrolled in this observational study and divided into 2 groups: group 1, patients with DM (n = 72) and group 2, patients without DM (n = 340). The overall in-hospital mortality rate for both groups combined was 20.2% and was higher in group 1 than in group 2 (41.7% vs. 16.5%, p < 0.01). Compared to patients without DM, patients with DM were older and associated with higher incidence of chronic diseases, less drug abuse, higher creatinine levels, and increased risk of Staphylococcus aureus infection (all p < 0.05). Moreover, they were more likely to have atypical clinical presentation and were associated with longer IE diagnosis time (all p < 0.05). In multivariable analysis, DM is an independent and significant predictor of mortality. The prognosis of IE patients with DM is still poor. Early identification and more aggressive treatment may be considered in IE patients with DM.

Liraglutide Inhibits Endothelial-to-Mesenchymal Transition and Attenuates Neointima Formation after Endovascular Injury in Streptozotocin-Induced Diabetic Mice.

Hyperglycaemia causes endothelial dysfunction, which is the initial process in the development of diabetic vascular complications. Upon injury, endothelial cells undergo an endothelial-to-mesenchymal transition (EndMT), lose their specific marker, and gain mesenchymal phenotypes. This study investigated the effect of liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, on EndMT inhibition and neointima formation in diabetic mice induced by streptozotocin. The diabetic mice with a wire-induced vascular injury in the right carotid artery were treated with or without liraglutide for four weeks. The degree of neointima formation and re-endothelialisation was evaluated by histological assessments. Endothelial fate tracing revealed that endothelium-derived cells contribute to neointima formation through EndMT in vivo. In the diabetic mouse model, liraglutide attenuated wire injury-induced neointima formation and accelerated re-endothelialisation. In vitro, a high glucose condition (30 mmol/L) triggered morphological changes and mesenchymal marker expression in human umbilical vein endothelial cells (HUVECs), which were attenuated by liraglutide or Activin receptor-like 5 (ALK5) inhibitor SB431542. The inhibition of AMP-activated protein kinase (AMPK) signaling by Compound C diminished the liraglutide-mediated inhibitory effect on EndMT. Collectively, liraglutide was found to attenuate neointima formation in diabetic mice partially through EndMT inhibition, extending the potential therapeutic role of liraglutide.

Associations with the In-Hospital Survival Following Extracorporeal Membrane Oxygenation in Adult Acute Fulminant Myocarditis.

BACKGROUND: Acute fulminant myocarditis (AFM) is a serious disease that progresses rapidly, and leads to failing respiratory and circulatory systems. When medications fail to reverse the patient's clinical course, extracorporeal membrane oxygenation (ECMO) is considered the most effective, supportive and adjunct strategy. In this paper we analyzed our experience in managing AFM with ECMO support. METHODS: During October 2003 and February 2017, a total of 35 patients (≥18 years) were enrolled in the study. Twenty patients survived, and another 15 patients expired. General demographics, the hemodynamic condition, timing of ECMO intervention, and laboratory data were compared for the survival and non-survival groups. Univariate and multivariate Cox regression analyses were performed to identify the associations with in-hospital mortality following ECMO use in this situation. RESULTS: The survival rate was 57.1% during the in-hospital period. The average age, gender, severity of the hemodynamic condition, and cardiac rhythm were similar between the survival and non-survival groups. Higher serum lactic acid (initial and 24 h later), higher peak cardiac biomarkers, higher incidence of acute kidney injury and the need for hemodialysis were noted in the non-survival group. Higher 24-h lactic acid levels and higher peak troponin-I levels were associated with in-hospital mortality. CONCLUSIONS: When ECMO was used for AFM, related cardiogenic shock and decompensated heart failure, higher peak serum troponin-I levels and 24-h serum lactic acid levels following ECMO use were independently associated with in-hospital mortality.

Deletion of RasGRF1 Attenuated Interstitial Fibrosis in Streptozotocin-Induced Diabetic Cardiomyopathy in Mice through Affecting Inflammation and Oxidative Stress.

BACKGROUND: Diabetic cardiomyopathy (DCM) is characterized by cardiac fibrosis and stiffness, which often develops into heart failure. This study investigated the role of Ras protein-specific guanine nucleotide releasing factor 1 (RasGRF1) in the development of DCM. METHODS: Forty-eight mice were divided into four groups (n = 12 per group): Group 1: Wild-type (WT) mice, Group 2: RasGRF1 deficiency (RasGRF1-/-) mice. Group 3: Streptozotocin (STZ)-induced diabetic WT mice, Group 4: STZ-induced diabetic RasGRF1-/- mice. Myocardial functions were assessed by cardiac echography. Heart tissues from all of the mice were investigated for cardiac fibrosis, inflammation, and oxidative stress markers. RESULTS: Worse impaired diastolic function with elevation serum interleukin (IL)-6 was found in the diabetic group compared with the non-diabetic groups. Serum IL-6 levels were found to be elevated in the diabetic compared with the non-diabetic groups. However, the diabetic RasGRF1-/- mice exhibited lower serum IL-6 levels and better diastolic function than the diabetic WT mice. The diabetic RasGRF1-/- mice were associated with reduced cardiac inflammation, which was shown by lower invading inflammation cells, lower expression of matrix metalloproteinase 9, and less chemokines compared to the diabetic WT mice. Furthermore, less oxidative stress as well as extracellular matrix deposition leading to a reduction in cardiac fibrosis was also found in the diabetic RasGRF1-/- mice compared with the diabetic WT mice. CONCLUSION: The deletion of RasGRF1 attenuated myocardial fibrosis and improved cardiac function in diabetic mice through inhibiting inflammation and oxidative stress.

Melatonin attenuated the brain damage and cognitive impairment partially through MT2 melatonin receptor in mice with chronic cerebral hypoperfusion.

BACKGROUND: Vascular cognitive impairment (VCI) is a spectrum of cognitive impairment caused by various chronic diseases including aging, hypertension, and diabetes mellitus. Oxidative and inflammatory reactions induced by chronic cerebral hypoperfusion (CHP) are believed to cause VCI. Melatonin is reported to possess anti-oxidation and anti-inflammation effects. This study was designed to investigate the effect and mechanisms of melatonin in CHP mice model. RESULTS: The behavioral function results revealed that CHP mice were significantly impaired when compared with the control. Melatonin improved the cognitive function, but the addition of MT2 receptor antagonist reversed the improvement. The IHC staining showed melatonin significantly improved WM lesions and gliosis in CHP mice. Again, the addition of MT2 receptor antagonist to melatonin worsened the WM lesion and gliosis. Similar results were also found for mRNA and protein expressions of oxidative reaction and inflammatory cytokines. MATERIALS AND METHOD: Forty C57BL/6 mice were divided into four groups: Group 1: sham control; Group 2: CHP mice; Group 3: CHP with melatonin treatment; Group 4: CHP-melatonin and MT2 receptor antagonist (all groups n = 10). Working memory was assessed with Y-arm test at day-28 post-BCAS (bilateral carotid artery stenosis). All mice were sacrificed at day-30 post-BCAS. The immunohistochemical (IHC) staining was used for white matter (WM) damage and gliosis. The expression of mRNA and proteins about inflammatory and oxidative reaction were measured and compared between groups. CONCLUSIONS: Partially through MT2 receptor, melatonin is effective for CHP-induced brain damage.

Thirty-Day and One-Year Clinical Outcomes of Bioresorbable Vascular Scaffold Implantation: A Single-Center Experience.

BACKGROUND: Available data on the use of the Bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, CA) in real-world patients is limited, particularly in Asian populations. The aim of this study was to assess clinical outcomes of patients treated with a BVS in real-world practice in Taiwan. METHODS: This study focused on 156 patients with coronary artery disease and a total of 249 lesions who received BVS implantation from October 2012 to October 2015. The study's primary endpoint was major adverse cardiac event (MACE), such as a myocardial infarction (MI), target vessel revascularization (TVR), target lesion revascularization (TLR), definite or possible scaffold thrombosis, cardiovascular death, and all-cause mortality during the thirty-day follow-up period. The secondary endpoint was MACE during the one-year follow-up period. Additionally, the composite clinical secondary endpoint was target lesion failure (TLF), which was called device-oriented composite endpoint. RESULTS: The average age of the patients was 60.34 ± 10.15 years, and 81.4% were male. The average of Syntax score was 12.42 ± 8.77 points. 44.2 % lesions were type B2 or C. At 31 days, one patient experienced a MACE (1/156) the composite of two TLF (2/249) with ST elevation MI, which was related to scaffold thrombosis. At one-year, 5.1 % (8/156) of the patients experienced a MACE and 3.6% (9/249) of the lesions experienced a TLF. There was no cardiovascular or all-cause mortality in the 30-day follow-up. The one-year cardiovascular and all-cause mortality rates were each 1.3%, respectively. Diabetes, ostial lesion, bifurcation lesion, and non-standard dual anti-platelet therapy (DAPT) were the strong associations of one-year TLF. CONCLUSIONS: Even with difficult and complex lesions of patients in this study, acceptable outcomes were achieved with low definite or possible scaffold thrombosis rates after BVS implantation. And despite anatomical issues, it is important to complete standard DAPT.

Anemia: A significant cardiovascular mortality risk after ST-segment elevation myocardial infarction complicated by the comorbidities of hypertension and kidney disease.

BACKGROUND: The effect of anemia on patients with ST-segment elevation myocardial infarction (STEMI) remains a controversial issue. The aim of this study was to explore the effect of anemia on STEMI patients. METHODS AND RESULTS: From January 2005 to December 2014, 1751 patients experienced STEMI checked serum hemoglobin initially before any administration of fluids or IV medications. 1751 patients then received primary percutaneous intervention immediately. A total of 1388 patients were enrolled in the non-anemia group because their serum hemoglobin level was more than 13 g/L in males, and 12 g/L in females. A total of 363 patients were enrolled in the anemia group because their serum hemoglobin level was less than 13 g/L in males, and 12 g/L in females. Higher incidences of major adverse cerebral cardiac events (22.9% vs. 33.8%; p<0.001) were also noted in the anemia group, and these were related to higher incidence of cardiovascular mortality (6.5% vs. 20.4%; p<0.001). A higher incidence of all-cause mortality (8.6% vs. 27.7%; p<0.001) was also noted in the anemia group. A Kaplan-Meier curve of one-year cardiovascular mortality showed significant differences between the non-anemia and anemia group in all patients (P<0.001), and the patients with hypertension (P<0.001), and chronic kidney disease (CKD) (P = 0.011). CONCLUSION: Anemia is a marker of an increased risk in one-year cardiovascular mortality in patients with STEMI. If the patients have comorbidities such as hypertension, or CKD, the effect of anemia is very significant.