In silico exploration of lignin peroxidase for unraveling the degradation mechanism employing lignin model compounds

Lignin peroxidase is a heme-containing biocatalyst, well-known for its diverse applications in the fields from environmental chemistry to biotechnology. LiP-mediated oxidative catalysis is H₂O₂-dependent, and can oxidize phenolic, and non-phenolic substrates by oxidative cleavage of the C–C and C–O bonds of lignin. In contrast to fungi-derived LiP, the binding affinity of bacterial-derived LiP to lignin at the molecular level is poorly known to date. Tremendous wet-lab studies have been unveiled that provide degradation and biotransformation information on kraft lignin, whilst studies on the completely transformed compounds and the degradation of each transformed compounds simultaneously during degradation are scarce. To gain an understanding of the degradation process using docking, and MDS based studies, we assessed the binding affinity of selected lignin model compounds with bacterial origin LiP and validated such docked complexes exploiting 30 ns molecular dynamics simulations. We selected and picked a total of 12 lignin model compounds for molecular modeling analysis, namely two chlorinated lignin model compounds (monomer) (2-chlorosyringaldehyde and 5-chlorovanillin), eight standard lignin model compounds (veratryl alcohol, syringyl alcohol, sinapyl alcohol, methyl hydroquinone, guaiacol, coniferyl alcohol, catechol, and 4-methoxy phenol), while, two 4-O-5, and β-O-4 linkage-based multimeric model compounds (dimer: 2-methoxy-6-(2-methoxy-4-methylphenoxy)-4-methylphenol; trimer: syringyl β-O-4 syringyl β-O-4 sinapyl alcohol). Far more specific binding residues were observed from XP-Glide docking, as TYR, HIP (protonated histidine), PHE, VAL, ASP, THR, LYS and GLN. The binding affinity was confirmed by the Gibbs free energy or binding energy (ΔG) score; furthermore, it is found that the maximum binding energy seems to be observed for 4-methoxyphenol with a Glide score of −3.438 with Pi–Pi stacking and H-bond type bonding interactions, whilst the lowest XP Gscore as −8.136 with Pi–Pi stacking and H-bond (side chain) type bonding interactions were found for the trimer model compound. The docked complexes were further evaluated for deep rigorous structural and functional fluctuation analyses through high-performance molecular dynamics simulations-DESMOND, after a post simulation run of 30 ns. The RMSD trajectory analyses of the protein-ligands were found to be in the equilibrium state at the end of simulation run for multimeric lignin model compounds. In addition, ionic ligand–protein interaction occurs among chlorinated compounds, while hydrophobic and H-bond contacts have frequently been observed in all lignin-model compounds. The findings herein demonstrate that bacterial LiP can effectively catalyze multiple lignin model compounds, and it might further be used as an effective tool for sustainable mitigation of diverse environmental contaminants.

The findings herein demonstrate that bacterial LiP can effectively catalyze multiple lignin model compounds, and it might further be used as an effective tool for sustainable mitigation of diverse environmental contaminants.     

Spontaneous left atrial echo contrast,mitral annular systolic velocity,and left atrial appendage late emptying velocity in predicting improvement of left atrial function after percutaneous balloon mitral valvuloplasty

Background

Thromboembolic events are the major cause of morbidity and mortality in patients with mitral stenosis (MS). This study aims to investigate left atrial spontaneous echo contrast (LA SEC), mitral annular systolic velocity (Sa‐wave), left atrial appendage (LAA) late emptying velocity (LAAEV), LAA filling velocity (LAAFV) pre‐ and postpercutaneous balloon mitral valvuloplasty (PBMV) for MS. This also aims to study the association of LA SEC with inflammatory marker, high‐sensitivity C‐reactive protein (hs‐CRP) in MS.

Methods

The study population consisted of 100 patients with symptomatic MS with sinus rhythm who underwent PBMV. Transthoracic echo (TTE), tissue Doppler imaging (TDI), and transesophageal echo (TEE) examinations were carried out before and 14 days following PBMV. High‐sensitivity C‐reactive protein (hs‐CRP) was measured at the time of admission.

Results

The mean age was 33.2 ± 10.3 years with female preponderance (71%). There was a decrease in SEC grading, (pre‐PBMV 2.8 ± 0.9 and post‐PBMV 0.4 ± 0.1; P < .01), increase in LAAEV (pre‐PBMV 23.0 ± 7.9 cm/s and post‐PBMV 40.9 ± 8.4 cm/s; P < .01), and LAAFV (pre‐PBMV 31.8 ± 9.3 cm/s and post‐PBMV 51.2 ± 8.7 cm/s; P < .01).A significant positive correlation was present between LAAEV and Sa‐wave (r = .52, P < .01). Correlation between hs‐CRP and SEC was positive and significant (r = .33, P < .01). Optimal cutoff value of hs‐CRP for prediction of moderate to dense SEC was >2.3 mg/dL, the cutoff value of Sa‐wave was≤ 5.5 cm/s for prediction of the presence of inactive LAA (LAAEV < 25 cm/s).

Conclusion

Mitral annular systolic velocity (Sa‐wave) is an independent predictor of inactive LAA and a useful parameter in estimating inactive LAA in MS. Sa‐wave and hs‐CRP are independent predictors for SEC. PBMV improves LAA function in patients with MS.     

Live donor liver transplantation for antitubercular drug-induced acute liver failure

Antitubercular therapy (ATT)-induced hepatotoxicity is often over looked and active tuberculosis is considered a contraindication for liver transplantation, however it might be the only lifesaving option to certain patients of acute liver failure (ALF) due to ATT. We have assessed the outcome of live donor liver transplantation in ATT-induced ALF. A retrospective analysis of all the cases of ALF that underwent liver transplantation from 2006 to 2014 at the Amrita Institute of Medical Sciences was done. A total of seven (7.7%) patients with ATT-induced ALF who had underwent live donor liver transplantation were included in the study. Out of seven patients, three (42.8%) had established diagnosis of tuberculosis and the remaining (58.2%) patients were started on ATT empirically. The median duration of ATT intake was 2 months. All the patients underwent live donor liver transplant as they met King’s College criteria, and their model for end-stage liver disease score was above 35 on admission, receiving graft from first degree relatives. Histopathology of explant liver showed pan acinar necrosis. Restarting of ATT after transplant was individualized. It was restarted only in two (28%) patients with prior sputum-positive pulmonary tuberculosis after a median time of 27 days after transplant. ATT was not restarted in rest of the (72%) patients. Postoperative mortality was seen in two (28%) patients due to conditions that masquerade the ATT-induced acute liver failure. The overall survival rate was 71.4% with a median follow up of 22 months. Live donor-related transplantation is feasible option in ATT-induced acute liver failure. Restarting of ATT post liver transplant is feasible and should be individualized along with frequent monitoring of immunosuppressant levels; however, if the primary diagnosis of tuberculosis was empirical, reintroduction of ATT can be omitted.     

Lung transplant in end-staged chronic obstructive pulmonary disease (COPD) patients: a concise review

Lung transplantation is commonly used for patients with end-stage lung disease. However, there is continuing debate on the optimal operation for patients with chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. Single-lung transplantation (SLT) provides equivalent short- and medium-term results compared with bilateral lung transplantation (BLT), but long-term survival appears slightly better in BLT recipients (especially in patients with COPD). The number of available organs for lung transplantation also influences the choice of operation. Recent developments suggest that the organ donor shortage is not as severe as previously thought, making BLT a possible alternative for more patients. Among the different complications, re-implantation edema, infection, rejection, and bronchial complications predominate. Chronic rejection, also called obliterative bronchiolitis syndrome, is a later complication which can be observed in about half of the patients. Improvement in graft survival depends greatly in improvement in prevention and management of complications. Despite such complications, graft survival in fibrosis patients is greater than spontaneous survival on the waiting list; idiopathic fibrosis is associated with the highest mortality on the waiting list. Patients should be referred early for the pre-transplantation work-up because individual prognosis is very difficult to predict.     

Congenital long QT syndrome: A case report

The congenital long QT syndrome (LQTS) is characterized by abnormally prolonged ventricular repolarization due to inherited defects in cardiac sodium and potassium channels, which predispose the patients to syncope, seizure like activity, ventricular arrhythmias, and sudden cardiac death. Early diagnosis and preventive treatment are instrumental in preventing sudden cardiac deaths in patients with the congenital LQTS. The diagnostic criteria for congenital LQTS are based on certain electrocardiographic findings, clinical findings and findings of epinephrine stress test. Recently genotype specific electrocardiographic pattern in the congenital LQTS has also been described. Recent studies suggest feasibility of genotype specific treatment of LQTS and, in near future, mutation specific treatment will probably become a novel approach to this potentially fatal syndrome. We describe one case that fulfilled the electrocardiographic, historical diagnostic criteria and epinephrine stress test suggestive of LQT syndrome.     

Angiographic management of pseudoaneurysms of gastroduodenal artery following endoscopic sphincterotomy

Gastrointestinal bleeding follows endoscopic sphincterotomy in 1 % to 10 % of patients. We report two cases of bleeding from pseudoaneurysms of the gastroduodenal artery occurring as a complication of endoscopic sphincterotomy.     

Trends in intracranial meningioma surgery and outcome: a Nationwide Inpatient Sample database analysis from 2001 to 2010

The objective of the present study was to analyze the risk of in-patient mortality, adverse outcome, practice patterns and regional variations in patients who underwent intracranial meningioma surgery in the United States between 2001 and 2010. We performed a retrospective cohort study using the Nationwide Inpatient Sample database. In-patient mortality and adverse outcome at discharge were the outcome predictors. Multivariate analyses were done to analyze the patient, hospital and physician characteristics. The annual case-volume of patients with meningioma increased from 2001 to 2010 by 40 %. The in-patient mortality rate remained the same at 1.3 % and the rate of adverse discharge disposition remained at 35 % between 2001 and 2010. Caucasian female patients in younger age group with private insurance who underwent treatment at a high case-volume center had the best outcomes. In older patients (≥70 years), the in-patient mortality rate decreased by 25 % whereas the adverse discharge disposition rate increased by 19 %. Patients treated at high case-volume centers and by high case-volume physicians had lower rates of in-patient mortality (P < 0.05) and adverse outcome at discharge (P = 0 < 0.05). There was a 54 % decrease in the number of hospitals performing one surgery/year through the decade. A 2 % relative decrease in mortality was observed in lowest volume hospitals. Though the highest increase in admission charges through the decade was seen in hospitals located in the north-east (165 % relative increase), the highest relative decrease in mortality and morbidity was observed in hospitals located in the mid-west and the south (67.6  and 22 % respectively).     

Margins in Skin Excision Biopsies: Principles and Guidelines

Skin biopsies are usually undertaken to confirm a clinical diagnosis, to remove a lesion, and to determine the adequacy of excised tissue margin. A surgical margin is technically defined as the “edge” of the tissue removed. The term is especially pertinent when the tissue excised is suspected of being involved by a malignant process. One of the most important predictive and prognostic factors of a malignant lesion is whether the margins of the resected specimen are involved by the tumor or not. The purpose of this review is to provide an insight into grossing of a skin biopsy specimen with emphasis on techniques and reporting of excision biopsy margins.     

Changes in Liver Congestion in Patients with Budd–Chiari Syndrome following Endovascular Interventions: Assessment with Transient Elastography

Purpose

Transient elastography (TE) is routinely used for noninvasive staging of hepatic fibrosis. The objective of the present study was to investigate the role of TE (FibroScan) in determining changes in liver congestion in patients with Budd–Chiari syndrome (BCS) treated by endovascular interventions and determine the effects of pretreatment Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) fibrosis score on posttreatment liver stiffness (LS).