Coronary artery disease in post-COVID patients: a prospective study

Background: Corona virus disease 2019 or COVID-19 is defined as infectious illness caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). The cardiovascular manifestations of COVID-19 has been a topic of immense interest amongst epidemiologists, physicians and cardiologists alike. Cytokine storm seen in patients with COVID-19 is known to cause damage to multiple organs including cardiac myocytes. Coronary arteries are also affected by direct damage as well as cytokine mediated injury to coronary endothelial cells.Methods: This was a prospective study conducted in the department of cardiology of a tertiary care hospital. 40 patients recovered from COVID-19 and having symptoms related to coronary artery disease were included in this study on the basis of a predefined inclusion and exclusion criteria. The presenting complaints such as chest pain, breathlessness and fatigue were asked for and were documented. An informed written consent was obtained from all the participants. A standard Judkins technique was used to do coronary angiography. Severity of stenosis was assessed in all the cases. The statistical analysis was done using SSPS 21.0 software. P value less than 0.05 was taken as statistically significant.Results: Out of 40 post COVID-19 patients presenting with symptoms attributable to coronary artery disease there were 34 (85%) males and 6 (15%) females with a M:F ratio of 1:0.17. The mean age of male and female patients was found to be 51.33±6.47 years and 44.50±6.82 respectively. 12 (30%) patients had history of hypertension, 8 (20%) had history of diabetes mellitus. 3 (7.5%) patients had history of asthma. Chest pain (95%), breathlessness (67.5%), reduced exertional capacity (55%) and diaphoresis (40%) were common presenting complaints. Slow flow due to endothelial dysfunction was the most common single finding and was seen in 8 (20%) patients. In 7 (17.5%) 51-60% stenosis with thrombosis was found whereas in 6 (15%) patients 81-90% stenosis with thrombosis was seen. In 3 (15%) patients 70-80% stenosis with thrombosis was found and in remaining 3 (7.5%) total occlusion was seen.Conclusions: A high index of suspicion and timely intervention is necessary to diagnose and manage coronary artery disease in post covid patients

Adipose-Derived Mesenchymal Stem Cells Treated with Growth Differentiation Factor-5 Express Tendon-Specific Markers

A sensitive spectrophotometric method for the analysis of isoniazid, lisinopril dihydrate, amoxicillin trihydrate, ampicillin trihydrate, glucosamine sulfate, phenylpropanolamine hydrochloride and gabapentin is described. The analysis is based on the reaction of drug molecules with ninhydrin and sodium molybdate mixture to give Ruhemann's purple product with maximum absorbance (lambda(max)) at 570 nm. The statistical analysis of intra-day and inter-day estimation of drugs as well as comparison with reported methods demonstrated high precision and accuracy of the proposed method. The method was successfully applied to the analysis of pharmaceutical preparations. The procedure was suitable for quality control application

Local Deuteration Enables NMR Observation of Methyl Groups in Proteins from Eukaryotic and Cell‐Free Expression Systems

Therapeutically relevant proteins such as GPCRs, antibodies and kinases face clear limitations in NMR studies due to the challenges in site-specific isotope labeling and deuteration in eukaryotic expression systems. Here we describe an efficient and simple method to observe the methyl groups of leucine residues in proteins expressed in bacterial, eukaryotic or cell-free expression systems without modification of the expression protocol. The method relies on simple stereo-selective 13C-labeling and deuteration of leucine that alleviates the need for additional deuteration of the protein. The spectroscopic benefits of “local” deuteration are examined in detail through Forbidden Coherence Transfer (FCT) experiments and simulations. The utility of this labeling method is demonstrated in the cell-free synthesis of bacteriorhodopsin and in the insect-cell expression of the RRM2 domain of human RBM39

Local Deuteration Enables NMR Observation of Methyl Groups in Proteins from Eukaryotic and Cell‐Free Expression Systems

Therapeutically relevant proteins such as GPCRs, antibodies and kinases face clear limitations in NMR studies due to the challenges in site-specific isotope labeling and deuteration in eukaryotic expression systems. Here we describe an efficient and simple method to observe the methyl groups of leucine residues in proteins expressed in bacterial, eukaryotic or cell-free expression systems without modification of the expression protocol. The method relies on simple stereo-selective 13C-labeling and deuteration of leucine that alleviates the need for additional deuteration of the protein. The spectroscopic benefits of “local” deuteration are examined in detail through Forbidden Coherence Transfer (FCT) experiments and simulations. The utility of this labeling method is demonstrated in the cell-free synthesis of bacteriorhodopsin and in the insect-cell expression of the RRM2 domain of human RBM39

Aromatic 19F-13C TROSY: a background-free approach to probe biomolecular structure, function, and dynamics

Atomic-level information about the structure and dynamics of biomolecules is critical for an understanding of their function. Nuclear magnetic resonance (NMR) spectroscopy provides unique insights into the dynamic nature of biomolecules and their interactions, capturing transient conformers and their features. However, relaxation-induced line broadening and signal overlap make it challenging to apply NMR spectroscopy to large biological systems. Here we took advantage of the high sensitivity and broad chemical shift range of 19F nuclei and leveraged the remarkable relaxation properties of the aromatic 19F-13C spin pair to disperse 19F resonances in a two-dimensional transverse relaxation-optimized spectroscopy spectrum. We demonstrate the application of 19F-13C transverse relaxation-optimized spectroscopy to investigate proteins and nucleic acids. This experiment expands the scope of 19F NMR in the study of the structure, dynamics, and function of large and complex biological systems and provides a powerful background-free NMR probe

Outcomes of Allogeneic Hematopoietic Cell Transplantation in T-cell Prolymphocytic Leukemia: A Contemporary Analysis from the Center for International Blood and Marrow Transplant Research.

BACKGROUND T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive malignancy with limited treatment options and poor long-term survival. Previous studies of allogeneic hematopoietic cell transplantation (alloHCT) for T-PLL are limited by small numbers, and descriptions of patient and transplant characteristics and outcomes after alloHCT are sparse. OBJECTIVE To describe outcomes of alloHCT in T-PLL and identify predictors of post-transplant relapse and survival. STUDY DESIGN We conducted an analysis of data using the Center for International Blood and Marrow Transplant Research (CIBMTR) database on 266 patients with T-PLL who underwent alloHCT during 2008-2018. RESULTS The 4-year rates of overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM) were 30.0% (95% CI, 23.8-36.5%), 25.7% (95% CI, 20-32%), 41.9% (95% CI, 35.5-48.4%), and 32.4% (95% CI, 26.4-38.6%), respectively. In multivariable analyses, three variables were associated with inferior OS: myeloablative conditioning (MAC) (hazard ratio [HR] 2.18, p<0.0001); age older than 60 years (HR 1.61, p=0.0053); and suboptimal performance status defined by Karnofsky Performance Status (KPS) <90 (HR 1.53, p=0.0073). MAC also was associated with increased TRM (HR 3.31, p<0.0001), increased cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) (HR 2.94, p=0.0011) and an inferior disease-free survival (HR 1.86, p=0.0004). Conditioning intensity was not associated with relapse; however stable disease/progression correlated with increased risk of relapse (HR 2.13, p=0.0072). Both in vivo T cell depletion (TCD) as part of conditioning and KPS <90 were associated with worse TRM and inferior DFS. Total Body Irradiation was not found to have any significant effect on OS, DFS or TRM. CONCLUSION Our data showed that reduced-intensity conditioning without in vivo T-cell depletion (that is, without ATG or alemtuzumab) prior to alloHCT was associated with long-term disease-free survival in patients with T-PLL who were 60 or younger or who had KPS >90 or had chemo-sensitive disease