Enhanced cardiac expression of two isoforms of matrix metalloproteinase-2 in experimental diabetes mellitus.

BackgroundDiabetic cardiomyopathy (DM CMP) is defined as cardiomyocyte damage and ventricular dysfunction directly associated with diabetes independent of concomitant coronary artery disease or hypertension. Matrix metalloproteinases (MMPs), especially MMP-2, have been reported to underlie the pathogenesis of DM CMP by increasing extracellular collagen content.PurposeWe hypothesized that two discrete MMP-2 isoforms (full length MMP-2, FL-MMP-2; N-terminal truncated MMP-2, NTT-MMP-2) are induced by high glucose stimulation in vitro and in an experimental diabetic heart model.MethodsRat cardiomyoblasts (H9C2 cells) were examined to determine whether high glucose can induce the expression of the two isoforms of MMP-2. For the in vivo study, we used the streptozotocin-induced DM mouse heart model and age-matched controls. The changes of each MMP-2 isoform expression in the diabetic mice hearts were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical stains were conducted to identify the location and patterns of MMP-2 isoform expression. Echocardiography was performed to compare and analyze the changes in cardiac function induced by diabetes.ResultsQuantitative RT-PCR and immunofluorescence staining showed that the two MMP-2 isoforms were strongly induced by high glucose stimulation in H9C2 cells. Although no definite histologic features of diabetic cardiomyopathy were observed in diabetic mice hearts, left ventricular systolic dysfunction was determined by echocardiography. Quantitative RT-PCR and IHC staining showed this abnormal cardiac function was accompanied with the increases in the mRNA levels of the two isoforms of MMP-2 and related to intracellular localization.ConclusionTwo isoforms of MMP-2 were induced by high glucose stimulation in vitro and in a Type 1 DM mouse heart model. Further study is required to examine the role of these isoforms in DM CMP

MGOS: A library for molecular geometry and its operating system

The geometry of atomic arrangement underpins the structural understanding of molecules in many fields. However, no general framework of mathematical/computational theory for the geometry of atomic arrangement exists. Here we present "Molecular Geometry (MG)'' as a theoretical framework accompanied by "MG Operating System (MGOS)'' which consists of callable functions implementing the MG theory. MG allows researchers to model complicated molecular structure problems in terms of elementary yet standard notions of volume, area, etc. and MGOS frees them from the hard and tedious task of developing/implementing geometric algorithms so that they can focus more on their primary research issues. MG facilitates simpler modeling of molecular structure problems; MGOS functions can be conveniently embedded in application programs for the efficient and accurate solution of geometric queries involving atomic arrangements. The use of MGOS in problems involving spherical entities is akin to the use of math libraries in general purpose programming languages in science and engineering. (C) 2019 The Author(s). Published by Elsevier B.V

Direct and indirect mortality impacts of the COVID-19 pandemic in the United States, March 1, 2020 to January 1, 2022

Excess mortality studies provide crucial information regarding the health burden of pandemics and other large-scale events. Here, we used time series approaches to separate the direct contribution of SARS-CoV-2 infections on mortality from the indirect consequences of pandemic interventions and behavior changes in the United States. We estimated deaths occurring in excess of seasonal baselines stratified by state, age, week and cause (all causes, COVID-19 and respiratory diseases, Alzheimer’s disease, cancer, cerebrovascular disease, diabetes, heart disease, and external causes, including suicides, opioids, accidents) from March 1, 2020 to April 30, 2021. Our estimates of COVID-19 excess deaths were highly correlated with SARS-CoV-2 serology, lending support to our approach. Over the study period, we estimate an excess of 666,000 (95% Confidence Interval (CI) 556000, 774000) all-cause deaths, of which 90% could be attributed to the direct impact of SARS-CoV-2 infection, and 78% were reflected in official COVID-19 statistics. Mortality from all disease conditions rose during the pandemic, except for cancer. The largest direct impacts of the pandemic were seen in mortality from diabetes, Alzheimer’s, and heart diseases, and in age groups over 65 years. In contrast, the largest indirect consequences of the pandemic were seen in deaths from external causes, which increased by 45,300 (95% CI 30,800, 59,500) and were statistically linked to the intensity of non-pharmaceutical interventions. Within this category, increases were most pronounced in mortality from accidents and injuries, drug overdoses, and assaults and homicides, while the rate of death from suicides remained stable. Younger age groups suffered the brunt of these indirect effects. Overall, on a national scale, the largest consequences of the COVID-19 pandemic are attributable to the direct impact of SARS-CoV-2 infections; yet, the secondary impacts dominate among younger age groups, in periods of stricter interventions, and in mortality from external causes. Further research on the drivers of indirect mortality is warranted to optimize interventions in future pandemics

Identification of New Proteins in Follicular Fluid from Mature Human Follicles by Direct Sample Rehydration Method of Two-Dimensional Polyacrylamide Gel Electrophoresis

Human follicular fluid (HFF) includes various biologically active proteins which can affect follicle growth and oocyte fertilization. Thus far, these proteins from mature follicles in human follicular fluid have been poorly characterized. Here, two-dimensional polyacrylamide gel electrophoresis (2-DE) with matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) was used to identify new proteins in HFF. Mature follicular fluids were obtained from five females after oocyte collection during in vitro fertilization (IVF). We directly rehydrated HFF samples, obtained high-resolution 2-DE maps, and processed them for 2-DE and MALDI-MS. One hundred eighty spots were detected and 10 of these spots were identified. By the 2-DE database, six of them had been reported, as proteins already existing in HFF. Hormone sensitive lipase (HSL), Unnamed protein product 1 (UPP1), Unnamed protein product 2 (UPP2), and apolipoprotein A-IV precursor were newly detected. HSL and apolipoprotein A-IV participate in lipid metabolism. UPP1 has a homology with selenocysteine lyase. We found by RT-PCR that these genes are expressed from human primary granulosa cells. The proteins identified here may emerge as potential candidates for specific functions during folliculogenesis, hormone secretion regulation, or oocyte maturation. Further functional analysis of these proteins is necessitated to determine their biological implications

Validation of quick sequential organ failure assessment score for poor outcome prediction among emergency department patients with suspected infection

Objective The quick sequential organ failure assessment (qSOFA) score, which includes mentation, systolic blood pressure, and respiratory rate, was developed to identify serious sepsis in out-of-hospital or emergency department (ED) settings. We evaluated the ability of the qSOFA score to predict poor outcome in South Korean ED patients with suspected infection. Methods The qSOFA score was calculated for adult ED patients with suspected infection. Patients who received intravenous or oral antibiotics in the ED were considered to have infection. In-hospital mortality rate, admission rate, intensive care unit (ICU) admission rate, length of hospital stay (LOS), and lactate levels were compared between the qSOFA score groups. Receiver operating characteristic curves and area under the receiver operating characteristic curve values for in-hospital mortality were calculated according to qSOFA cut-off points and lactate levels. Results Of 2,698 patients, in-hospital mortality occurred in 134 (5.0%). The mortality rate increased with increasing qSOFA score (2.2%, 6.4%, 17.5%, and 42.4% for qSOFA scores 0, 1, 2, and 3, respectively, P<0.001). The admission rate, ICU admission rate, LOS, and lactate level also increased with increasing qSOFA score (all P<0.001). The area under the receiver operating characteristic curve values for predicting in-hospital mortality associated with qSOFA score, lactate ≥2 mmol/L, and lactate ≥4 mmol/L were 0.719 (95% confidence interval [CI], 0.670 to 0.768), 0.657 (95% CI, 0.603 to 0.710), and 0.632 (95% CI, 0.571 to 0.693), respectively. Conclusion Patients with a higher qSOFA score had higher admission, ICU admission, and in-hospital mortality rates, longer LOS, and higher lactate level. The qSOFA score showed better performance for predicting poor outcome than lactate level

Prospective analysis of video head impulse tests in patients with acute posterior circulation stroke

BackgroundVideo head impulse tests (vHITs), assessing the vestibulo-ocular reflex (VOR), may be helpful in the differential diagnosis of acute dizziness. We aimed to investigate vHITs in patients with acute posterior circulation stroke (PCS) to examine whether these findings could exhibit significant abnormalities based on lesion locations, and to evaluate diagnostic value of vHIT in differentiating dizziness between PCS and vestibular neuritis (VN).MethodsWe prospectively recruited consecutive 80 patients with acute PCS and analyzed vHIT findings according to the presence of dorsal brainstem stroke (DBS). We also compared vHIT findings between PCS patients with dizziness and a previously studied VN group (n = 29). Receiver operating characteristic (ROC) analysis was performed to assess the performance of VOR gain and its asymmetry in distinguishing dizziness between PCS and VN.ResultsPatients with PCS underwent vHIT within a median of 2 days from stroke onset. Mean horizontal VOR gain was 0.97, and there was no significant difference between PCS patients with DBS (n = 15) and without (n = 65). None exhibited pathologic overt corrective saccades. When comparing the PCS group with dizziness (n = 40) to the VN group (n = 29), patients with VN demonstrated significantly lower mean VOR gains in the ipsilesional horizontal canals (1.00 vs. 0.57, p &lt; 0.001). VOR gain and their asymmetry effectively differentiated dizziness in the PCS from VN groups, with an area under the ROC curve of 0.86 (95% CI 0.74–0.98) and 0.91 (95% CI 0.83–0.99, p &lt; 0.001), respectively.ConclusionSignificantly abnormal vHIT results were rare in patients with acute PCS, even in the presence of DBS. Moreover, vHIT effectively differentiated dizziness between PCS and VN, highlighting its potential for aiding differential diagnosis of acute dizziness

Tristetraprolin down-regulates IL-23 expression in colon cancer cells.

mRNA 3&apos;UTR demonstrated that the ARE cluster between the third and fifth AREs was responsible for TTP-mediated destabilization of IL-23 mRNA. A RNA electrophoretic mobility shift assay confirmed that TTP binds to this ARE cluster. Taken together, these results demonstrate that TTP acts as a negative regulator of IL-23 gene expression in mouse colon cancer cells and suggest its potential application as a novel therapeutic target to control IL-23-mediated tumor promotion