High Sensitivity Cardiac Troponin-T STAT in Type 2 Diabetes Mellitus Patients and Healthy Individuals: A Comparative Study

Introduction: Diabetes Mellitus (DM) is a metabolic disorder that shares the phenotype of hyperglycaemia, with several factors contributing to the disease, including decreased insulin secretion and glucose utilisation, as well as increased glucose production. There is a strong association between DM and Cardiovascular Disease (CVD). High-sensitivity cardiac troponin T (hs-cTnT), which is a marker of subclinical myocardial damage, is used in the risk stratification of asymptomatic individuals. Aim: To estimate and compare hs-cTnT Short Turn Around Time (STAT) levels in diabetic patients without Acute Myocardial Infarction (AMI) with age and sex matched controls and also to investigate the correlation between hs-cTnT STAT and Glycated Haemoglobin (HbA1c) levels. Materials and Methods: A comparative cross-sectional study was conducted in the Department of Biochemistry and Outpatient Clinic, Department of Medicine, Government Medical College, Kozhikode, Kerala, India, from April 2019 to April 2020. The study subjects were divided into two groups: Group 1 consisted of 58 patients with Type 2 Diabetes Mellitus (T2DM) without AMI, and Group 2 comprised 58 healthy individuals who were age and sex matched. No specific sampling technique was employed. After obtaining consent, T2DM patients who attended the outpatient clinic were evaluated with fasting blood glucose, HbA1c, Electrocardiogram (ECG), and hs-cTnT STAT estimation. Controls were selected and evaluated for the same from apparently healthy bystanders of other patients, medical and paramedical staff, and others willing to participate. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) version 22.0 software. Results: The mean value of Fasting Blood Sugar (FBS) and HbA1c was higher in T2DM patients compared to healthy individuals. hs-cTnT showed a positive moderate correlation with HbA1c (rho=0.53), which was statistically significant (p-value<0.001). Simple linear regression analysis showed that in the case group, for a 1% increase in HbA1c levels, there was a 2.38 unit increase in hs-cTnT levels, which was statistically significant (p-value<0.001). Conclusion: hs-cTnT levels are significantly elevated in T2DM patients without overt CVD compared to age and sex matched healthy individuals. T2DM is a risk factor for increased levels of biomarkers for atherosclerotic CVD, and proper glycaemic control reduces the levels of hs-cTnT in T2DM patients

Retinal repair by transplantation of photoreceptor precursors

Photoreceptor loss causes irreversible blindness in many retinal diseases. Repair of such damage by cell transplantation is one of the most feasible types of central nervous system repair; photoreceptor degeneration initially leaves the inner retinal circuitry intact and new photoreceptors need only make single, short synaptic connections to contribute to the retinotopic map. So far, brain- and retina-derived stem cells transplanted into adult retina have shown little evidence of being able to integrate into the outer nuclear layer and differentiate into new photoreceptors(1-4). Furthermore, there has been no demonstration that transplanted cells form functional synaptic connections with other neurons in the recipient retina or restore visual function. This might be because the mature mammalian retina lacks the ability to accept and incorporate stem cells or to promote photoreceptor differentiation. We hypothesized that committed progenitor or precursor cells at later ontogenetic stages might have a higher probability of success upon transplantation. Here we show that donor cells can integrate into the adult or degenerating retina if they are taken from the developing retina at a time coincident with the peak of rod genesis(5). These transplanted cells integrate, differentiate into rod photoreceptors, form synaptic connections and improve visual function. Furthermore, we use genetically tagged postmitotic rod precursors expressing the transcription factor Nrl (ref. 6) ( neural retina leucine zipper) to show that successfully integrated rod photoreceptors are derived only from immature post-mitotic rod precursors and not from proliferating progenitor or stem cells. These findings define the ontogenetic stage of donor cells for successful rod photoreceptor transplantation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62596/1/nature05161.pd

Report of depressive symptoms on waiting list and mortality after liver and kidney transplantation: a prospective cohort study

International audienceABSTRACT: BACKGROUND: Little research has explored pre-transplantation psychological factors as predictors of outcome after liver or kidney transplantation. Our objective is to determine whether report of depressive symptoms on waiting list predicts outcome of liver and kidney transplantation. METHODS: Patients on waiting list for liver or kidney transplantation were classified for report or non-report of depressive symptoms on waiting list. 339 were transplanted 6 months later on average, and followed prospectively. The main outcome measures were graft failure and mortality 18 months post-transplantation. RESULTS: Among the 339 patients, 51.6% reported depressive symptoms on waiting list, 16.5% had a graft failure and 7.4% died post-transplantation. Report of depressive symptoms on waiting list predicted a 3 to 4-fold decreased risk of graft failure and mortality 18-months post-transplantation, independently from age, gender, current cigarette smoking, anxiety symptoms, main primary diagnosis, UNOS score, number of comorbid diagnoses and history of transplantation. Data were consistent for liver and kidney transplantations. Other baseline predictive factors were: for graft failure, the main primary diagnosis and a shorter length since this diagnosis, and for mortality, older age, male gender and the main primary diagnosis. CONCLUSION: Further studies are needed to understand the underlying mechanisms of the association between report of depressive symptoms on waiting list and decreased risk of graft failure and mortality after transplantation

The Role of SDF-1-CXCR4/CXCR7 Axis in the Therapeutic Effects of Hypoxia-Preconditioned Mesenchymal Stem Cells for Renal Ischemia/Reperfusion Injury

In vitro hypoxic preconditioning (HP) of mesenchymal stem cells (MSCs) could ameliorate their viability and tissue repair capabilities after transplantation into the injured tissue through yet undefined mechanisms. There is also experimental evidence that HP enhances the expression of both stromal-derived factor-1 (SDF-1) receptors, CXCR4 and CXCR7, which are involved in migration and survival of MSCs in vitro, but little is known about their role in the in vivo therapeutic effectiveness of MSCs in renal ischemia/reperfusion (I/R) injury. Here, we evaluated the role of SDF-1-CXCR4/CXCR7 pathway in regulating chemotaxis, viability and paracrine actions of HP-MSCs in vitro and in vivo. Compared with normoxic preconditioning (NP), HP not only improved MSC chemotaxis and viability but also stimulated secretion of proangiogenic and mitogenic factors. Importantly, both CXCR4 and CXCR7 were required for the production of paracrine factors by HP-MSCs though the former was only responsible for chemotaxis while the latter was for viability. SDF-1α expression was upregulated in postischemic kidneys. After 24 h systemical administration following I/R, HP-MSCs but not NP-MSCs were selectively recruited to ischemic kidneys and this improved recruitment was abolished by neutralization of CXCR4, but not CXCR7. Furthermore, the increased recruitment of HP-MSCs was associated with enhanced functional recovery, accelerated mitogenic response, and reduced apoptotic cell death. In addition, neutralization of either CXCR4 or CXCR7 impaired the improved therapeutic potential of HP-MSCs. These results advance our knowledge about SDF-1-CXCR4/CXCR7 axis as an attractive target pathway for improving the beneficial effects of MSC-based therapies for renal I/R

Transcriptome Analysis of the Model Protozoan, Tetrahymena thermophila, Using Deep RNA Sequencing

Background: The ciliated protozoan Tetrahymena thermophila is a well-studied single-celled eukaryote model organism for cellular and molecular biology. However, the lack of extensive T. thermophila cDNA libraries or a large expressed sequence tag (EST) database limited the quality of the original genome annotation. Methodology/Principal Findings: This RNA-seq study describes the first deep sequencing analysis of the T. thermophila transcriptome during the three major stages of the life cycle: growth, starvation and conjugation. Uniquely mapped reads covered more than 96 % of the 24,725 predicted gene models in the somatic genome. More than 1,000 new transcribed regions were identified. The great dynamic range of RNA-seq allowed detection of a nearly six order-of-magnitude range of measurable gene expression orchestrated by this cell. RNA-seq also allowed the first prediction of transcript untranslated regions (UTRs) and an updated (larger) size estimate of the T. thermophila transcriptome: 57 Mb, or about 55 % of the somatic genome. Our study identified nearly 1,500 alternative splicing (AS) events distributed over 5.2 % of T. thermophila genes. This percentage represents a two order-of-magnitude increase over previous EST-based estimates in Tetrahymena. Evidence of stage-specific regulation of alternative splicing was also obtained. Finally, our study allowed us to completely confirm about 26.8 % of the genes originally predicted by the gene finder, to correct coding sequence boundaries an

Mesenchymal stem cells: from experiment to clinic

There is currently much interest in adult mesenchymal stem cells (MSCs) and their ability to differentiate into other cell types, and to partake in the anatomy and physiology of remote organs. It is now clear these cells may be purified from several organs in the body besides bone marrow. MSCs take part in wound healing by contributing to myofibroblast and possibly fibroblast populations, and may be involved in epithelial tissue regeneration in certain organs, although this remains more controversial. In this review, we examine the ability of MSCs to modulate liver, kidney, heart and intestinal repair, and we update their opposing qualities of being less immunogenic and therefore tolerated in a transplant situation, yet being able to contribute to xenograft models of human tumour formation in other contexts. However, such observations have not been replicated in the clinic. Recent studies showing the clinical safety of MSC in several pathologies are discussed. The possible opposing powers of MSC need careful understanding and control if their clinical potential is to be realised with long-term safety for patients

D, L-Sulforaphane loaded Fe3O4@ gold core shell nanoparticles: A potential sulforaphane delivery system

A novel design of gold-coated iron oxide nanoparticles was fabricated as a potential delivery system to improve the efficiency and stability of d, l-sulforaphane as an anticancer drug. To this purpose, the surface of gold-coated iron oxide nanoparticles was modified for sulforaphane delivery via furnishing its surface with thiolated polyethylene glycol-folic acid and thiolated polyethylene glycol-FITC. The synthesized nanoparticles were characterized by different techniques such as FTIR, energy dispersive X-ray spectroscopy, UV-visible spectroscopy, scanning and transmission electron microscopy. The average diameters of the synthesized nanoparticles before and after sulforaphane loading were obtained ∼ 33 nm and ∼ 38 nm, respectively, when ∼ 2.8 mmol/g of sulforaphane was loaded. The result of cell viability assay which was confirmed by apoptosis assay on the human breast cancer cells (MCF-7 line) as a model of in vitro-cancerous cells, proved that the bare nanoparticles showed little inherent cytotoxicity, whereas the sulforaphane-loaded nanoparticles were cytotoxic. The expression rate of the anti-apoptotic genes (bcl-2 and bcl-xL), and the pro-apoptotic genes (bax and bak) were quantified, and it was found that the expression rate of bcl-2 and bcl-xL genes significantly were decreased when MCF-7 cells were incubated by sulforaphane-loaded nanoparticles. The sulforaphane-loaded into the designed gold-coated iron oxide nanoparticles, acceptably induced apoptosis in MCF-7 cells

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with &gt;80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes