Percutaneous transluminal mitral commissurotomy in pregnant women with severe mitral stenosis

Background: Mitral stenosis tends to worsen during pregnancy because of the increase in the cardiac output and the heart rate. In nonresponders to medical therapy, percutaneous transluminal mitral commissurotomy (PTMC) may be performed when there is a suitable valvular anatomy. In this study, we aimed to investigate the clinical and fetal outcomes of pregnant women with mitral stenosis who underwent PTMC. Methods: Thirty-one patients undergoing PTMC during pregnancy were enrolled in this study. The mitral valve area (MVA), the transmitral valve mean gradient (MVMG), and the severity of mitral regurgitation were assessed pre- and postprocedurally by transthoracic and transesophageal echocardiography. The radiation time was measured during the procedure. The patients were followed up during pregnancy, and the neonates were monitored for weight, height, the head circumference, the birth Apgar score, and the adverse effects of radiation for at least 12 months. Results: PTMC was successfully performed on 29 (93.5) patients. No maternal death or pulmonary edema was reported. The mean MVA significantly increased (from 0.73±0.17 cm2to 1.28±0.24 cm2; P<0.001), and the mean MVMG significantly decreased (from 19.62±5.91 mmHg to 8.90±4.73 mmHg; P<0.001) after the procedure. A significant decrease in the systolic pulmonary artery pressure was also detected. Mitral regurgitation did not increase in severity in 16 (51.6) patients. There was no significant relationship between the Apgar score, weight, height, and the head circumference at birth and at the radiation time. Conclusion: In our series, PTMC during pregnancy was a safe and effective procedure. Lowering the radiation time with low frame-count techniques confers a significant decrease in radiation-related complications. © 2019, Tehran Heart Center. All Rights Reserved

Modeling healthcare authorization and claim submissions using the openEHR dual-model approach

<p>Abstract</p> <p>Background</p> <p>The TISS standard is a set of mandatory forms and electronic messages for healthcare authorization and claim submissions among healthcare plans and providers in Brazil. It is not based on formal models as the new generation of health informatics standards suggests. The objective of this paper is to model the TISS in terms of the openEHR archetype-based approach and integrate it into a patient-centered EHR architecture.</p> <p>Methods</p> <p>Three approaches were adopted to model TISS. In the first approach, a set of archetypes was designed using ENTRY subclasses. In the second one, a set of archetypes was designed using exclusively ADMIN_ENTRY and CLUSTERs as their root classes. In the third approach, the openEHR ADMIN_ENTRY is extended with classes designed for authorization and claim submissions, and an ISM_TRANSITION attribute is added to the COMPOSITION class. Another set of archetypes was designed based on this model. For all three approaches, templates were designed to represent the TISS forms.</p> <p>Results</p> <p>The archetypes based on the openEHR RM (Reference Model) can represent all TISS data structures. The extended model adds subclasses and an attribute to the COMPOSITION class to represent information on authorization and claim submissions. The archetypes based on all three approaches have similar structures, although rooted in different classes. The extended openEHR RM model is more semantically aligned with the concepts involved in a claim submission, but may disrupt interoperability with other systems and the current tools must be adapted to deal with it.</p> <p>Conclusions</p> <p>Modeling the TISS standard by means of the openEHR approach makes it aligned with ISO recommendations and provides a solid foundation on which the TISS can evolve. Although there are few administrative archetypes available, the openEHR RM is expressive enough to represent the TISS standard. This paper focuses on the TISS but its results may be extended to other billing processes. A complete communication architecture to simulate the exchange of TISS data between systems according to the openEHR approach still needs to be designed and implemented.</p

Induction of oxidative stress as a mechanism of action of chemopreventive agents against cancer

Prevention is a promising option for the control of cancer. Cellular redox changes have emerged as a pivotal and proximal event in cancer. In this review, we provide a brief background on redox biochemistry, discuss the important distinction between redox signalling and oxidative stress, and outline the ‘multiple biological personalities' of reactive oxygen and nitrogen species: at low concentrations they protect the cell; at higher concentrations they can damage many biological molecules, such as DNA, proteins, and lipids; and, as we argue here, they may also prevent cancer by initiating the death of the transformed cell. Nitric oxide-donating aspirin is discussed as an instructive example: it generates a state of oxidative stress through which it affects several redox-sensitive signalling pathways, leading ultimately to the elimination of the neoplastic cell via apoptosis or necrosis. As additional examples, we discuss the chemopreventive n–3 polyunsaturated fatty acids and conventional nonsteroidal anti-inflammatory drugs, which induce cell death through redox changes. We conclude that modulation of redox biochemistry represents a fruitful approach to cancer prevention

Structural Conformers of (1,3-Dithiol-2-ylidene)ethanethioamides: The Balance Between Thioamide Rotation and Preservation of Classical Sulfur-Sulfur Hypervalent Bonds

The reaction of N-(2-phthalimidoethyl)-N-alkylisopropylamines and S2Cl2 gave 4-N-(2-phthalimidoethyl)-N-alkylamino-5-chloro-1,2-dithiol-3-thiones that quantitatively cycloadded to dimethyl or diethyl acetylenedicarboxylate to give stable thioacid chlorides, which in turn reacted with one equivalent of aniline or a thiole to give thioanilides or a dithioester. Several compounds of this series showed atropisomers that were studied by a combination of dynamic NMR, simulation of the signals, conformational analysis by DFT methods, and single crystal X-ray diffraction, showing a good correlation between the theoretical calculations, the experimental values of energies, and the preferred conformations in the solid state. The steric hindering of the crowded substitution at the central amine group was found to be the reason for the presence of permanent atropisomers in this series of compounds and the cause of a unique disposition of the thioxo group at close-to-right angles with respect to the plane defined by the 1,3-dithiole ring in the dithiafulvene derivatives, thus breaking the sulfur–sulfur hypervalent bond that is always found in this kind of compounds.Ministerio de Economıá y Competitividad, Spain (Project CTQ2012- 31611), Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo (Project BU246A12-1), and the European Commission, Seventh Framework Programme (Project SNIFFER FP7-SEC-2012-312411

Hydrogen sulphide-induced hypometabolism in human-sized porcine kidneys

Background Since the start of organ transplantation, hypothermia-forced hypometabolism has been the cornerstone in organ preservation. Cold preservation showed to protect against ischemia, although post-transplant injury still occurs and further improvement in preservation techniques is needed. We hypothesize that hydrogen sulphide can be used as such a new preservation method, by inducing a reversible hypometabolic state in human sized kidneys during normothermic machine perfusion. Methods Porcine kidneys were connected to an ex-vivo isolated, oxygen supplemented, normothermic blood perfusion set-up. Experimental kidneys (n = 5) received a 85mg NaHS infusion of 100 ppm and were compared to controls (n = 5). As a reflection of the cellular metabolism, oxygen consumption, mitochondrial activity and tissue ATP levels were measured. Kidney function was assessed by creatinine clearance and fractional excretion of sodium. To rule out potential structural and functional deterioration, kidneys were studied for biochemical markers and histology. Results Hydrogen sulphide strongly decreased oxygen consumption by 61%, which was associated with a marked decrease in mitochondrial activity/function, without directly affecting ATP levels. Renal biological markers, renal function and histology did not change after hydrogen sulphide treatment. Conclusion In conclusion, we showed that hydrogen sulphide can induce a controllable hypometabolic state in a human sized organ, without damaging the organ itself and could thereby be a promising therapeutic alternative for cold preservation under normothermic conditions in renal transplantation

Erratum: COMPARE CPM-RMI trial: Intramyocardial transplantation of autologous bone marrow-derived CD133+ cells and MNCs during CABG in patients with recent MI: A phase II/III, multicenter, placebo-controlled, randomized, double-blind clinical trial. (Cell Journal (2018) 20:3 (449) DOI: 10.22074/cellj.2018.5197)

This article published in Cell J (Yakhteh), Vol 20, No 2, Jul-Sep 2018, on pages 267-277, four affiliations (1, 4, 5, and 10) were changed based on authors request. © 2018 Royan Institute (ACECR). All rights reserved

COMPARE CPM-RMI Trial: Intramyocardial transplantation of autologous bone marrow-derived CD133+ Cells and MNCs during CABG in patients with recent MI: A Phase II/III, multicenter, placebo-controlled, randomized, double-blind clinical trial

Objective: The regenerative potential of bone marrow-derived mononuclear cells (MNCs) and CD133+ stem cells in the heart varies in terms of their pro-angiogenic effects. This phase II/III, multicenter and double-blind trial is designed to compare the functional effects of intramyocardial autologous transplantation of both cell types and placebo in patients with recent myocardial infarction (RMI) post-coronary artery bypass graft. Materials and Methods: This was a phase II/III, randomized, double-blind, placebo-controlled trial COMPARE CPM-RMI (CD133, Placebo, MNCs - recent myocardial infarction) conducted in accordance with the Declaration of Helsinki that assessed the safety and efficacy of CD133 and MNCs compared to placebo in patients with RMI. We randomly assigned 77 eligible RMI patients selected from 5 hospitals to receive CD133+ cells, MNC, or a placebo. Patients underwent gated single photon emission computed tomography assessments at 6 and 18 months post-intramyocardial transplantation. We tested the normally distributed efficacy outcomes with a mixed analysis of variance model that used the entire data set of baseline and between-group comparisons as well as within subject (time) and group�time interaction terms. Results: There were no related serious adverse events reported. The intramyocardial transplantation of both cell types increased left ventricular ejection fraction by 9 95% confidence intervals (CI): 2.14% to 15.78%, P=0.01 and improved decreased systolic wall thickening by -3.7 (95% CI: -7.07 to -0.42, P=0.03). The CD133 group showed significantly decreased non-viable segments by 75% (P=0.001) compared to the placebo and 60% (P=0.01) compared to the MNC group. We observed this improvement at both the 6- and 18-month time points. Conclusion: Intramyocardial injections of CD133+ cells or MNCs appeared to be safe and efficient with superiority of CD133+ cells for patients with RMI. Although the sample size precluded a definitive statement about clinical outcomes, these results have provided the basis for larger studies to confirm definitive evidence about the efficacy of these cell types (Registration Number: NCT01167751). © 2018 Royan Institute (ACECR). All Rights Reserved

Induction of cell cycle changes and modulation of apoptogenic/anti-apoptotic and extracellular signaling regulatory protein expression by water extracts of I'm-Yunity™ (PSP)

BACKGROUND: I'm-Yunity™ (PSP) is a mushroom extract derived from deep-layer cultivated mycelia of the patented Cov-1 strain of Coriolus versicolor (CV), which contains as its main bioactive ingredient a family of polysaccharo-peptide with heterogeneous charge properties and molecular sizes. I'm-Yunity™ (PSP) is used as a dietary supplement by cancer patients and by individuals diagnosed with various chronic diseases. Laboratory studies have shown that I'm-Yunity™ (PSP) enhances immune functions and also modulates cellular responses to external challenges. Recently, I'm-Yunity™ (PSP) was also reported to exert potent anti-tumorigenic effects, evident by suppression of cell proliferation and induction of apoptosis in malignant cells. We investigate the mechanisms by which I'm-Yunity™ (PSP) elicits these effects. METHODS: Human leukemia HL-60 and U-937 cells were incubated with increasing doses of aqueous extracts of I'm-Yunity™ (PSP). Control and treated cells were harvested at various times and analyzed for changes in: (1) cell proliferation and viability, (2) cell cycle phase transition, (3) induction of apoptosis, (4) expression of cell cycle, apoptogenic/anti-apoptotic, and extracellular regulatory proteins. RESULTS: Aqueous extracts of I'm-Yunity™ (PSP) inhibited cell proliferation and induced apoptosis in HL-60 and U-937 cells, accompanied by a cell type-dependent disruption of the G(1)/S and G(2)/M phases of cell cycle progression. A more pronounced growth suppression was observed in treated HL-60 cells, which was correlated with time- and dose-dependent down regulation of the retinoblastoma protein Rb, diminution in the expression of anti-apoptotic proteins bcl-2 and survivin, increase in apoptogenic proteins bax and cytochrome c, and cleavage of poly(ADP-ribose) polymerase (PARP) from its native 112-kDa form to the 89-kDa truncated product. Moreover, I'm-Yunity™ (PSP)-treated HL-60 cells also showed a substantial decrease in p65 and to a lesser degree p50 forms of transcription factor NF-κB, which was accompanied by a reduction in the expression of cyclooxygenase 2 (COX2). I'm-Yunity™ (PSP) also elicited an increase in STAT1 (signal transducer and activator of transcription) and correspondingly, decrease in the expression of activated form of ERK (extracellular signal-regulated kinase). CONCLUSION: Aqueous extracts of I'm-Yunity™ (PSP) induces cell cycle arrest and alterations in the expression of apoptogenic/anti-apoptotic and extracellular signaling regulatory proteins in human leukemia cells, the net result being suppression of proliferation and increase in apoptosis. These findings may contribute to the reported clinical and overall health effects of I'm-Yunity™ (PSP)

Profound Chemopreventative Effects of a Hydrogen Sulfide-Releasing NSAID in the APC(Min/+) Mouse Model of Intestinal Tumorigenesis

Canadian Institutes of Health Research grant to JL