Ionomic profiling of pericardial fluid in ischemic heart disease

Metals are essential cofactors that play a crucial role in heart function at the cell and tissue level. Information regarding the role of metals in the pericardial fluid and its ionome in ischemic heart disease (IHD) is limited. We aimed to determine the association of elements in pericardial fluid and serum samples of IHD patients and their correlation with systolic and diastolic function. IHD patients have been studied with systolic and diastolic dysfunction categorized on the basis of echocardiographic parameters. We measured concentrations of sixteen elements in the pericardial fluid and serum of 46 patients obtained during open heart surgery with IHD by ICP-MS. The levels of chromium and nickel in pericardial fluid were significantly higher as compared with serum samples of IHD patients (p < 0.05). The chromium, nickel and manganese levels in pericardial fluid were lower in patients with ejection fraction (EF) < 45% as compared to EF > 45% (p < 0.05). There was no significant difference in pericardial concentrations of elements in diastolic dysfunction grade 0–1 with 2 in IHD patients. We also found that decreased concentration of these elements in pericardial fluid is associated with decreased systolic function. These results suggest that pericardial fluid concentrations of these metals may reflect the extent of ischemic heart disease. These findings are hypothesis generating with regards to a role in the pathogenesis of the disorder.

Metals are essential cofactors that play a crucial role in heart function at the cell and tissue level.     

Molecular Dynamics Simulations to Decipher the Role of Phosphorylation of SARS-CoV-2 Nonstructural Proteins (nsps) in Viral Replication

Protein phosphorylation is a post-translational modification that enables various cellular activities and plays essential roles in protein interactions. Phosphorylation is an important process for the replication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To shed more light on the effects of phosphorylation, we used an ensemble of neural networks to predict potential kinases that might phosphorylate SARS-CoV-2 nonstructural proteins (nsps) and molecular dynamics (MD) simulations to investigate the effects of phosphorylation on nsps structure, which could be a potential inhibitory target to attenuate viral replication. Eight target candidate sites were found as top-ranked phosphorylation sites of SARS-CoV-2. During the process of molecular dynamics (MD) simulation, the root-mean-square deviation (RMSD) analysis was used to measure conformational changes in each nsps. Root-mean-square fluctuation (RMSF) was employed to measure the fluctuation in each residue of 36 systems considered, allowing us to evaluate the most flexible regions. These analysis shows that there are significant structural deviations in the residues namely nsp1 THR 72, nsp2 THR 73, nsp3 SER 64, nsp4 SER 81, nsp4 SER 455, nsp5 SER284, nsp6 THR 238, and nsp16 SER 132. The identified list of residues suggests how phosphorylation affects SARS-CoV-2 nsps function and stability. This research also suggests that kinase inhibitors could be a possible component for evaluating drug binding studies, which are crucial in therapeutic discovery research.     

Onychomycosis in Lahore, Pakistan

BACKGROUND: Onychomycosis, a common nail disorder, is caused by yeasts, dermatophytes, and nondermatophyte molds. These fungi give rise to diverse clinical presentations. The present study aimed to isolate the causative pathogens and to determine the various clinical patterns of onychomycosis in the population in Lahore, Pakistan. PATIENTS: In 100 clinically suspected cases, the diagnosis was confirmed by mycologic culture. Different clinical patterns were noted and correlated with causative pathogens. RESULTS: Seventy-two women (mean age, 32.6 +/- 14.8 years) and 28 men (mean age, 40.6 +/- 15.8 years) were studied. Fingernails were involved in 50%, toenails in 23%, and both fingernails and toenails in 27% of patients. The various clinical types noted were distolateral subungual onychomycosis (47%), candidal onychomycosis (36%), total dystrophic onychomycosis (12%), superficial white onychomycosis (3%), and proximal subungual onychomycosis (2%). Candida was the most common pathogen (46%), followed by dermatophytes (43%) (Trichophyton rubrum (31%), T. violaceum (5%), T. mentagrophytes (4%), T. tonsurans (2%), and Epidermophyton floccosum (1%) and nondermatophyte molds (11%) (Fusarium (4%), Scopulariopsis brevicaulis (2%), Aspergillus (2%), Acremonium (1%), Scytalidium dimidiatum (1%), and Alternaria (1%). CONCLUSIONS: Onychomycosis is more common in women of 20-40 years of age. Distolateral subungual onychomycosis and candidal onychomycosis are the most common clinical presentations, and Candida and T. rubrum are the major pathogens in Pakistan.     

Pathology of Suspected Acquired Immune Deficiency Syndrome in Children: A Study of Eight Cases

Biopsy and/or autopsy material from lymphoreticular and other organs was studied in 8 children with suspected acquired immune deficiency syndrome (AIDS). One or both parents of each of these children had one or more of the recognized risk factors for AIDS, such as intravenous drug abuse, prostitution, Haitian origin. The following histologic patterns were noted in the lymph nodes: (1) follicular hyperplasia with normocellular paracortex, (2) follicular hyperplasia with depletion of paracortex, and (3) atrophy of follicles with depletion of paracortex. Lymphoid interstitial pneumonitis (LIP), a previously unreported lesion in AIDS, was present in 4 cases. It is suggested that the pulmonary lymphoid lesion may be part of a more generalized lymphoid hyperplasia involving B cells. The gross and microscopic features of the thymus, available in 2 of the 8 cases, indicated that the immunologic defect in these children was not of congenital type. Pathologic findings can be helpful in the diagnosis of the syndrome when correlated with clinical and immunologic features of suspected cases and of the pulmonary lesion. The latter is of importance in deciding the type of therapy to be given for the pulmonary disease process.