Tracheal Allotransplantation-Lessons Learned.

Reconstruction of long tracheal defects still proves to be a challenge. Free fasciocutaneous flaps with cartilaginous struts or an allotransplant trachea have been reported but not been widely performed. This article reports with the experience of using a tracheal allotransplant in such a defect. A 43-year-old lady presented with adenoid cystic carcinoma involving the entire trachea from subglottic area up to the carina, leading to a life-threatening airway occlusion. After preliminary stenting, allotransplant trachea obtained from a brain-dead individual was revascularized in the forearm of the patient after mechanical decellularization to reduce the immune load and fulfil the need for immunosuppression in the background of active cancer. Subsequently, the trachea and larynx were resected. The vascularized neotrachea was transferred successfully into the neck. The patient did well initially but succumbed to a fatal hemorrhage due to innominate vein aneurysmal rupture on the 22nd day after the transplant. The technical details of resection, fabrication of the neotrachea, its transfer, and the lessons learnt in this tracheal allotransplant are described.

What makes non-cirrhotic portal hypertension a common disease in India? Analysis for environmental factors.

In India, an unexplained enteropathy is present in a majority of non-cirrhotic intrahepatic portal hypertension (NCIPH) patients. Small intestinal bacterial contamination and tropical enteropathy could trigger inflammatory stimuli and activate the endothelium in the portal venous system. Groundwater contaminated with arsenic is an environmental factor of epidemic proportions in large areas of India which has similar consequences. Von Willebrand factor (a sticky protein) expressed by activated endothelium may promote formation of platelet microthrombi and occlusion of intrahepatic portal vein branches leading to NCIPH. Environmental factors linked to suboptimal hygiene and sanitation, which enter through the gastrointestinal (GI) tract, predispose to platelet plugging onto activated endothelium in portal microcirculation. Thus, NCIPH, an example of poverty linked thrombophilia, is a disease mainly affecting the lower socio-economic strata of Indian population. Public health measures to improve sanitation, provide clean drinking water and eliminate arsenic contamination of drinking water are urgently needed. Till such time as these environmental factors are addressed, NCIPH is likely to remain 'an Indian disease'.

Effect of aspirin in vascular surgery in patients from a randomized clinical trial (POISE-2).

BACKGROUND: In the POISE-2 (PeriOperative ISchemic Evaluation 2) trial, perioperative aspirin did not reduce cardiovascular events, but increased major bleeding. There remains uncertainty regarding the effect of perioperative aspirin in patients undergoing vascular surgery. The aim of this substudy was to determine whether there is a subgroup effect of initiating or continuing aspirin in patients undergoing vascular surgery. METHODS: POISE-2 was a blinded, randomized trial of patients having non-cardiac surgery. Patients were assigned to perioperative aspirin or placebo. The primary outcome was a composite of death or myocardial infarction at 30 days. Secondary outcomes included: vascular occlusive complications (a composite of amputation and peripheral arterial thrombosis) and major or life-threatening bleeding. RESULTS: Of 10 010 patients in POISE-2, 603 underwent vascular surgery, 319 in the continuation and 284 in the initiation stratum. Some 272 patients had vascular surgery for occlusive disease and 265 had aneurysm surgery. The primary outcome occurred in 13·7 per cent of patients having aneurysm repair allocated to aspirin and 9·0 per cent who had placebo (hazard ratio (HR) 1·48, 95 per cent c.i. 0·71 to 3·09). Among patients who had surgery for occlusive vascular disease, 15·8 per cent allocated to aspirin and 13·6 per cent on placebo had the primary outcome (HR 1·16, 0·62 to 2·17). There was no interaction with the primary outcome for type of surgery (P = 0·294) or aspirin stratum (P = 0·623). There was no interaction for vascular occlusive complications (P = 0·413) or bleeding (P = 0·900) for vascular compared with non-vascular surgery. CONCLUSION: This study suggests that the overall POISE-2 results apply to vascular surgery. Perioperative withdrawal of chronic aspirin therapy did not increase cardiovascular or vascular occlusive complications. Registration number: NCT01082874 ( http://www.clinicaltrials.gov).

Stereo-, Regio-, and Chemoselective [3 + 2]-Cycloaddition of (2E,4E)-Ethyl 5-(Phenylsulfonyl)penta-2,4-dienoate with Various Azomethine Ylides, Nitrones, and Nitrile Oxides: Synthesis of Pyrrolidine, Isoxazolidine, and Isoxazoline Derivatives and a Computational Study.

One-pot chemo-, regio-, and stereoselective synthesis of series of heterocyclic and spiroheterocyclic compounds was accomplished through mono- and bis[3 + 2]-cycloaddition reactions of (2E,4E)-ethyl 5-(phenylsulfonyl)penta-2,4-dienoate as a dipolarophile with azomethine ylides, nitrones, and nitrile oxides in good yields. The structures of the products were established by spectroscopic techniques as well as by single-crystal XRD study, and DFT calculations were performed to further understand the mechanism of this [3 + 2]-cycloaddition reaction.

Indian folklore medicine in managing men's health and wellness.

India is a home for a large variety of plants with remarkable medicinal and pharmacological value. Traditional medicine in the form of Ayurveda, Siddha and Unani has used many of these plants since ancient days for treating and curing various ailments of the body. When it comes to issues related to reproductive health, people still hesitate to discuss and/or accept it openly and hence look for alternate and natural remedies. The various tribal populations distributed across different parts of the country still use these plant extracts in various formulations for maintenance of good health. The medical utilities of several of these plants have been documented; however, there are many more, whose potential is yet to be explored. This review discusses the role of various plants grown in the Indian subcontinent that have been widely used in maintaining various aspects of reproductive health in men such as infertility, aphrodisiac, contraception, libido, sexually transmitted infections and reproductive tract cancers as well as in treating chronic disorders.

The effects of over expressing aquaporins on the cryopreservation of hepatocytes.

During cryopreservation, aquaporins are critical in regulating water transport across cellular membranes and preventing osmotic damages. Hepatocytes express aquaporin (AQP) 0, 8, 9, 11, and 12; this study investigates whether increasing the localization of AQP8 on the cellular membrane would improve cell viability by increasing water transport during cryopreservation. Primary rat hepatocytes were cultured and treated with dibutyryl cAMP (Bt(2)cAMP) or glucagon to increase the expression of AQP8 at the cellular membrane via translocation. This phenomenon is verified through two experiments - confocal immunofluorescence microscopy and cell shrinkage analysis. The immunofluorescence results showed increase in AQP8 on the cellular membrane of treated cells, and cell shrinkage analysis showed an increase in water transport of treated cells compared to controls. Primary rat hepatocytes were treated with Bt(2)cAMP or glucagon and cryopreserved using standard protocols in a controlled rate freezer. This resulted in a significant increase in the cell viability on warming. These results indicate that Bt(2)cAMP or glucagon treated hepatocytes had increased expression of aquaporin in the cellular membrane, increased water transport during cryopreservation, and increased post-thaw viability.

Immune response and intestinal permeability in children with acute gastroenteritis treated with Lactobacillus rhamnosus GG: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Probiotics have a possible role in the treatment of pediatric acute gastroenteritis. We report the effect of the probiotic Lactobacillus rhamnosus GG (LGG) on intestinal function, immune response, and clinical outcomes in Indian children with cryptosporidial or rotavirus diarrhea. METHODS: Children with gastroenteritis aged 6 months to 5 years, testing positive for either rotavirus or Cryptosporidium species in stool (coinfections were excluded), were randomized to LGG (ATCC 53103) or placebo, once daily for 4 weeks. Baseline demographic and clinical details were obtained. Sera were tested for immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to Cryptosporidium and rotavirus, and the lactulose to mannitol ratio for intestinal permeability was determined at baseline and at the end of follow-up. RESULTS: Of the 124 children enrolled, 82 and 42 had rotavirus and cryptosporidial diarrhea, respectively. Median diarrheal duration was 4 days; one-third of the children had severe diarrhea. Baseline and clinical parameters were comparable between children receiving LGG and placebo. At the end of follow-up, fewer children with rotavirus diarrhea on LGG had repeated diarrheal episodes (25% vs 46%; P = .048) and impaired intestinal function (48% vs 72%; P = .027). Significant increase in IgG levels postintervention (456 vs 2215 EU; P = .003) was observed in children with rotavirus diarrhea receiving LGG. Among children with cryptosporidial diarrhea, those receiving LGG showed significant improvement in intestinal permeability. CONCLUSIONS: LGG has a positive immunomodulatory effect and may be useful in decreasing repeated episodes of rotavirus diarrhea. Improvement in intestinal function in children with rotavirus and cryptosporidial gastroenteritis emphasizes the role of probiotics in treating intestinal impairment after infection. CLINICAL TRIALS REGISTRATION: CTRI/2010/091/000339.

Serum cholinesterase is an excellent biomarker of liver cirrhosis.

BACKGROUND: Serum cholinesterase (ChE) is an enzyme synthesised by hepatocytes and its serum levels reflect the synthetic function of liver. METHODS: In patients with cirrhosis, liver function tests, PT INR and serum ChE levels were done within a week of enrolment. We studied 178 cirrhosis patients and 154 healthy controls prospectively. Receiver operator characteristics (ROC) curve analysis was employed to compute an optimal cut-off level to distinguish these groups. Correlation between ChE activity and serum bilirubin, albumin, PT INR and MELD score (Model for End-Stage Liver Disease) was analysed. RESULTS: Median serum ChE in cirrhotics was 1590 IU/L (110-8143) compared to controls 7886 IU/L (2022- 21673), p < 0.001. Serum ChE levels below 3506 had a 98.7% sensitivity and 80.3% specificity in predicting cirrhosis. Median serum ChE was higher (p < 0.001) in CC (n = 51) 4246 IU/L (680-8143) compared to DC (n = 127) 1324 IU/L (110-4550). ChE level less than 2385 IU/L had 80.1% sensitivity and 88.2% specificity in predicting DC. Follow-up levels in 25 patients showed good correlation with clinical course. The correlation coefficient between ChE and albumin was -0.67, 0.53 with PT INR and 0.59 with MELD score, (p < 0.001). CONCLUSIONS: Serum ChE is an excellent biomarker of cirrhosis with good sensitivity and specificity. It shows good correlation with serum albumin, PT INR and MELD score. Since it distinguishes DC from CC well, low levels in cirrhosis may serve as a useful prognostic marker of advanced liver disease. Long-term follow-up studies are warranted to define its exact role in clinical practice.

Graphene nanoribbon-PVA composite as EMI shielding material in the X band.

A very thin graphene nanoribbon/polyvinyl alcohol (GNR/PVA) composite film has been developed which is light weight and requires a very low concentration of filler to achieve electromagnetic interference (EMI) shielding as high as 60 dB in the X band. Atomic force microscope studies show very well conjugated filler concentration in the PVA matrix for varying concentrations of GNR supported by Raman spectroscopy data. The films show 14 orders of increase in conductivity with a GNR concentration of 0.75% [corrected] in PVA. This is possible because of the interconnected GNR network providing a very low percolation threshold as observed from the electrical measurements. Local density of states study of GNR using scanning tunnelling spectroscopy shows the presence of localized states near the Fermi energy. There are multiple advantages of GNR as an EMI shielding material in a polymer matrix. It has good dispersion in water, the conductive network in the composite shows very high electrical conductivity for a very low concentration of GNR and the presence of localized density of states near Fermi energy provides the spin states required for the absorbance of radiation energy in the X band.

3-[(4-Oxo-4H-thio-chromen-3-yl)meth-yl]-4H-thio-chromen-4-one.

The title mol-ecule, C19H12S2O2, lies on a twofold rotation axis. The thio-chromonone unit is essentially planar, with a maximum deviation of 0.0491 (14) Å. The dihedral angle between the thio-chromenone ring systems is 64.48 (4)°. In the crystal, there are weak π-π stacking inter-actions, with a centroid-centroid distance of 3.7147 (9) Å.

rac-7-Methyl-3-[(7-methyl-4-oxo-chro-man-3-yl)meth-yl]-4H-chromen-4-one.

In the racemic title compound, C21H18O4, the chromone ring is essentially planar [maximum deviation from the least-squares plane = 0.026 (3) Å], with a dihedral angle of 78.18 (12)° between the benzene rings of the chromanone and chromenone moieties. In the crystal, there are weak π-π stacking inter-actions [minimum ring centroid separation = 3.9286 (17) Å].

(2E,4E)-Ethyl 5-(2,4-di-chloro-phenyl-sulfon-yl)penta-2,4-dienoate.

In the title compound, C13H12Cl2O4S, both C=C double bonds adopt an E conformation. The S atom has a distorted tetra-hedral geometry with bond angles ranging from 103.03 (12) to 118.12 (13)°. The eth-oxy-carbonyl group is disordered over two sets of sites, with site-occupancy factors of 0.739 (11) and 0.261 (11). In the crystal, C-H⋯O inter-actions link the mol-ecules into chains mol-ecules running parallel to the a axis.

Novel molecular hybrid geometric-harmonic-Zagreb degree based descriptors and their efficacy in QSPR studies of polycyclic aromatic hydrocarbons.

The physicochemical characteristics of polycyclic aromatic compounds critical to environmental modelling such as octanol partition coefficients, solubility, lipophilicity, polarity and several equilibrium constants are functions of their underlying molecular structures, prompting the development of mathematical models to predict such characteristics for which experimental results are difficult to obtain. We propose twelve novel descriptors derived from geometric, harmonic and Zagreb degree-based descriptors and then test the effectiveness of these descriptors on a data set consisting of 55 benzenoid hydrocarbons of environmental importance. Our computations show that the proposed descriptors have a good linear correlation and predictive power when compared to the degree and distance type descriptors. We have also derived the QSPR expressions for four properties of a large series of polycyclic aromatics arising from circumscribing coronenes and show that a scaling factor can be deduced to derive physicochemical properties of such series up to 2D graphene sheets.

Focused panel sequencing points to genetic predisposition in non-cirrhotic intrahepatic portal hypertension patients in India.

OBJECTIVE: Non-cirrhotic intrahepatic portal hypertension (NCIPH), a portal microangiopathy affecting small portal vein radicles, is a disease of Indian sub-continent. NCIPH appears to be a complex disease with interactions between inherited and acquired factors, though the exact pathophysiological mechanism is unknown. We aimed at investigating the genetic variants that might contribute to susceptibility to NCIPH. METHODS: In this case-control study, we analyzed genes associated with microangiopathy-VWF-ADAMTS13 (von Willebrand factor and its cleavase enzyme - a disintegrin and matrix metalloprotease with thrombospondin type-1 motifs member 13) and alternative complement system vitamin B12 metabolism and with familial NCIPH. RESULT: Eighty-four Indian patients with liver biopsy-proven NCIPH (cases) and 103 healthy controls (matched for residential region of India) were included in the study. Targeted next-generation sequencing (NGS) panel, comprising 11 genes of interest, was done on 54 cases. Genotyping of selected variants was performed in 84 cases and 103 healthy controls. We identified variants in MBL2, CD46 and VWF genes either associated or predisposing to NCIPH. We also identified a single case with a novel compound heterozygous mutation in MBL2 gene, possibly contributing to development of NCIPH. CONCLUSION: In this first of a kind comprehensive gene panel study, multiple variants of significance have been noted, especially in ADAMTS13-VWF and complement pathways in NCIPH patients in India. Functional significance of these variants needs to be further studied.

Unsymmetrical tetrasubstituted ureas from tertiary carbamoylimidazole: activation by AlMe3.

An efficient and general method for the synthesis of unsymmetrical tetrasubstituted ureas from carbamoylimidazole is described. The conversion is achieved by the concurrent quarternization of the imidazole nitrogen and activation of amines with AlMe(3).

Direct inhibition of phospholipid scrambling activity in erythrocytes by potassium ions.

The exposure of phosphatidylserine (PS) at the cell surface plays a critical role in blood coagulation and serves as a macrophage recognition moiety for the engulfment of apoptotic cells. Previous observations have shown that a high extracellular [K(+)] and selective K(+) channel blockers inhibit PS exposure in platelets and erythrocytes. Here we show that the rate of PS exposure in erythrocytes decreases by approximately 50% when the intracellular [K(+)] increases from 0 to physiological concentrations. Using resealed erythrocyte membranes, we further show that lipid scrambling is inducible by raising the intracellular [Ca(2+)] and that K(+) ions have a direct inhibitory effect on this process. Lipid scrambling in resealed ghosts occurs in the absence of cell shrinkage and microvesicle formation, processes that are generally attributed to Ca(2+)-induced lipid scrambling in intact erythrocytes. Thus, opening of Ca(2+)-sensitive K(+) channels causes loss of intracellular K(+) that results in reduced intrinsic inhibitory effect of these ions on scramblase activity.

Weighted Mostar indices as measures of molecular peripheral shapes with applications to graphene, graphyne and graphdiyne nanoribbons.

In this study we consider relatively new bond-additive Mostar indices that appear to provide quantitative measures of peripheral shapes of molecules. We have computed weighted Mostar, edge-Mostar and total-Mostar indices of graphene, [Formula: see text]-types of graphyne and graphdiyne, which are of considerable interest owing to their novel properties and thus find applications in a number of areas such as sensors, catalysis, chemisorption and nanomedicine. We have implemented the results to analyse the weighted Mostar indices and have obtained exact analytical expressions for the title molecules. We propose that Mostar indices together with frontier molecular orbitals, and HOMO-LUMO gaps can provide measures of chemical reactivity and analysis of peripheral molecular shapes.

Fatty acids influence binding of cobalt to serum albumin in patients with fatty liver.

Human serum albumin binds ligands such as fatty acids and metals in circulation. Oxidative stress can modify albumin and affect ligand binding. This study examines the role of oxidative stress and fatty acids in modulating cobalt binding to albumin in patients with fatty liver. Elevated levels of malondialdehyde and protein carbonyls, indicative of oxidative stress were evident in serum of patients with fatty liver. A significant decrease in albumin-cobalt binding was also observed. Albumin isolated from patient serum also showed an increase in bound fatty acids. In vitro experiments indicated that while oxidant exposure or removal of fatty acids independently decreased cobalt binding to albumin, removal of fatty acids from the protein prior to oxidant exposure did not influence the oxidant effect on albumin-cobalt binding. These results suggest that oxidative stress and fatty acids on albumin can influence albumin-cobalt binding in patients with fatty liver by independent mechanisms.