Competition between In-Plane vs Above-Plane Configurations of Water with Aromatic Molecules: Non-Covalent Interactions in 1,4-Naphthoquinone-(H2O)1-3Complexes

Non-covalent interactions between aromatic molecules and water are fundamental in many chemical and biological processes, and their accurate description is essential to understand molecular relative configurations. Here we present the rotational spectroscopy study of the water complexes of the polycyclic aromatic hydrocarbon 1,4-naphthoquinone (1,4-NQ). In 1,4-NQ-(H2O)1,2, water molecules bind through O-H···O and C-H···O hydrogen bonds and are located on the plane of 1,4-NQ. For 1,4-NQ-(H2O)3, in-plane and above-plane water configurations are observed exhibiting O-H···O, C-H···O, and lone pair···π-hole interactions. The observation of different water arrangements for 1,4-NQ-(H2O)3 allows benchmarking theoretical methods and shows that they have great difficulty in predicting energy orderings due to the strong competition of C-H···O binding with πand π-hole interactions. This study provides important insight into water interactions with aromatic systems and the challenges in their modeling

Ruptured Sinus of Valsalva Aneurysm Causing Aorto–Atrial Fistula and Acute Heart Failure: A Rare Encounter

A ruptured sinus of Valsalva aneurysm as a cause of aorto–atrial fistula is very rare. We present the case of a 53-year-old female who presented with symptoms of acute heart failure and suspicion of an aorto–atrial fistula found on a transthoracic echocardiogram, which was confirmed on transesophageal echocardiography. A coronary angiogram showed normal coronary arteries but confirmed the right aorto–atrial fistula on aortogram. She underwent successful surgical repair of the fistula. Her postoperative echocardiogram showed a normal right atrium and right ventricle with no shunt. A ruptured sinus of Valsalva aneurysm is a devastating event and presents as acute heart failure. Prompt diagnosis and surgical repair is necessary to prevent mortality

Isolation of Bacillus producing Chitinase from Soil: Production and Purification of Chito-oligosaccharides from Chitin Extracted from Fresh Water Crustaceans and Antimicrobial Activity of Chitinase

In the present investigation Bacillus sp. strain was isolated and screened from the red soil collected from Doiwala region of Dehradun (U.K), India. Serial dilution technique was adopted to isolate the organism and was screened for its chitinolytic activity. The biochemical tests were performed to prove its validity. The microorganism was also screened by inoculating a loop full of the isolated strain in basic cresol red dye and incubated for about 18- 24 h. The conversion of colour of the red dye into purple (pH, 6.5- 8.8) was taken as an indication for the presence of Bacillus sp. Amylase production by the organism was also screened by introduction of iodine in the broth/agar culture having starch. The broth/agar medium having starch but no bacterial strain was used as the control. The disappearance of color confirmed the presence of Bacillus strain producing amylase which degrades the starch. The chitinous wastes were collected from fresh water crustaceans viz. fresh water crab (Potamon sp.) and fresh water prawn (Palaemon sp.) and the chitin extracted was used as the substrate for chitinase. The yield of chitin extracted from fresh water prawn (Palaemon sp.) was found to be comparatively higher than that of chitin extracted from fresh water crab (Potamon sp.). Standard colloidal chitin was used as the reference control. The enzyme activity of chitinase for degradation of chitin extracted from crab and prawn was compared. The results confirmed that chitinase activity for degradation of crab chitin was comparatively higher than that of degradation of prawn chitin. The enzyme activities were found to be 0.11 µg/ml/minute and 0.09 µg/ml/minute for degradation of crab and prawn chitin respectively. The antimicrobial activity of chitinase extracted was determined against the bacterial and fungal cultures. Potent antibacterial activity of chitinase was observed against the bacterial cultures but no antifungal activity was observed. The chitinase produced by the species was able to degrade the chitin and chito-oligosaccharides produced was separated by TLC and purified by HPLC

Circulating extracellular vesicles induce monocyte dysfunction and are associated with sepsis and high mortality in cirrhosis

BACKGROUND: Sepsis is common in cirrhosis and is often a result of immune dysregulation. Specific stimuli and pathways of inter-cellular communications between immune cells in cirrhosis and sepsis are incompletely understood. Immune cell-derived Extracellular Vesicles (EV) were studied to understand mechanisms of sepsis in cirrhosis. METHODS: Immune-cell derived EV were measured in cirrhosis patients [Child-Turcotte-Pugh (Child) score A, n=15; B n=16; C n=43 and Child-C with sepsis (n=38)], and healthy controls (HC, n=11). In-vitro and in-vivo functional relevance of EV in cirrhosis and associated sepsis was investigated. RESULTS: Monocyte, neutrophil and hematopoietic stem cells associated EV progressively increased with higher Child score (p0.3, p<0.001), which further increased in Child C sepsis than without sepsis(p<0.001); monocyte EV showing the highest association with disease stage [p=0.013; Odds ratio-4.14(1.34-12.42)]. A threshold level of monocyte EV of 53/µl predicted mortality in patients of Child C with sepsis [Odds ratio-6.2 (2.4-15.9), AUROC=0.76, p<0.01]. In vitro EV from cirrhotic with sepsis compared without sepsis, induced mobilization arrest in healthy monocytes within 4 hours (p=0.004), reduced basal oxygen consumption rate (p<0.001) and induced pro-inflammatory genes (p<0.05). The septic-EV on adoptive transfer to C57/BL6J mice, induced sepsis like condition within 24h with leukocytopenia (p=0.005), intrahepatic inflammation with increased CD11b+ cells (p=0.03) and bone marrow hyperplasia (p<0.01). CONCLUSION: Extracellular vesicles induce functional impairment in circulating monocytes and contribute to the development and perpetuation of sepsis. High levels of monocyte EV correlate with mortality and can help early stratification of sicker patients

Increased Expression of RUNX1 in Liver Correlates with NASH Activity Score in Patients with Non-Alcoholic Steatohepatitis (NASH)

Given the important role of angiogenesis in liver pathology, the current study investigated the role of Runt-related transcription factor 1 (RUNX1), a regulator of developmental angiogenesis, in the pathogenesis of non-alcoholic steatohepatitis (NASH). Quantitative RT-PCRs and a transcription factor analysis of angiogenesis-associated differentially expressed genes in liver tissues of healthy controls, patients with steatosis and NASH, indicated a potential role of RUNX1 in NASH. The gene expression of RUNX1 was correlated with histopathological attributes of patients. The protein expression of RUNX1 in liver was studied by immunohistochemistry. To explore the underlying mechanisms, in vitro studies using RUNX1 siRNA and overexpression plasmids were performed in endothelial cells (ECs). RUNX1 expression was significantly correlated with inflammation, fibrosis and NASH activity score in NASH patients. Its expression was conspicuous in liver non-parenchymal cells. In vitro, factors from steatotic hepatocytes and/or VEGF or TGF-beta significantly induced the expression of RUNX1 in ECs. RUNX1 regulated the expression of angiogenic and adhesion molecules in ECs, including CCL2, PECAM1 and VCAM1, which was shown by silencing or over-expression of RUNX1. Furthermore, RUNX1 increased the angiogenic activity of ECs. This study reports that steatosis-induced RUNX1 augmented the expression of adhesion and angiogenic molecules and properties in ECs and may be involved in enhancing inflammation and disease severity in NASH

Prospective, multicentre study of screening, investigation and management of hyponatraemia after subarachnoid haemorrhage in the UK and Ireland

Background: Hyponatraemia often occurs after subarachnoid haemorrhage (SAH). However, its clinical significance and optimal management are uncertain. We audited the screening, investigation and management of hyponatraemia after SAH. Methods: We prospectively identified consecutive patients with spontaneous SAH admitted to neurosurgical units in the United Kingdom or Ireland. We reviewed medical records daily from admission to discharge, 21 days or death and extracted all measurements of serum sodium to identify hyponatraemia (&lt;135 mmol/L). Main outcomes were death/dependency at discharge or 21 days and admission duration &gt;10 days. Associations of hyponatraemia with outcome were assessed using logistic regression with adjustment for predictors of outcome after SAH and admission duration. We assessed hyponatraemia-free survival using multivariable Cox regression. Results: 175/407 (43%) patients admitted to 24 neurosurgical units developed hyponatraemia. 5976 serum sodium measurements were made. Serum osmolality, urine osmolality and urine sodium were measured in 30/166 (18%) hyponatraemic patients with complete data. The most frequently target daily fluid intake was &gt;3 L and this did not differ during hyponatraemic or non-hyponatraemic episodes. 26% (n/N=42/164) patients with hyponatraemia received sodium supplementation. 133 (35%) patients were dead or dependent within the study period and 240 (68%) patients had hospital admission for over 10 days. In the multivariable analyses, hyponatraemia was associated with less dependency (adjusted OR (aOR)=0.35 (95% CI 0.17 to 0.69)) but longer admissions (aOR=3.2 (1.8 to 5.7)). World Federation of Neurosurgical Societies grade I–III, modified Fisher 2–4 and posterior circulation aneurysms were associated with greater hazards of hyponatraemia. Conclusions: In this comprehensive multicentre prospective-adjusted analysis of patients with SAH, hyponatraemia was investigated inconsistently and, for most patients, was not associated with changes in management or clinical outcome. This work establishes a basis for the development of evidence-based SAH-specific guidance for targeted screening, investigation and management of high-risk patients to minimise the impact of hyponatraemia on admission duration and to improve consistency of patient care

Stochastic behavior of a cold standby system with maximum repair time

The main aim of the present paper is to analyze the stochastic behavior of a cold standby system with concept of preventive maintenance, priority and maximum repair time. For this purpose, a stochastic model is developed in which initially one unit is operative and other is kept as cold standby. There is a single server who visits the system immediately as and when required. The server takes the unit under preventive maintenance after a maximum operation time at normal mode if one standby unit is available for operation. If the repair of the failed unit is not possible up to a maximum repair time, failed unit is replaced by new one. The failure time, maximum operation time and maximum repair time distributions of the unit are considered as exponentially distributed while repair and maintenance time distributions are considered as arbitrary. All random variables are statistically independent and repairs are perfect. Various measures of system effectiveness are obtained by using the technique of semi-Markov process and RPT. To highlight the importance of the study numerical results are also obtained for MTSF, availability and profit function