Molecular characterization,isolation, pathology and pathotyping of peafowl (Pavo cristatus) origin Newcastle disease virus isolates recovered from disease outbreaks in three states of India

Disease outbreak investigations were carried out in three states of Northern India namely Haryana (Rewari), Uttar Pradesh (Noida) and Delhi, where a total of 110 Indian peafowls (Pavo cristatus) showed sudden onset of nervous signs and died within a period of two weeks during June, 2012. The F (fusion) gene-based RT-PCR detection of Newcastle disease virus (NDV) in affected tissues confirmed the presence of the virus. Three NDV isolates were selected (one from each area under investigation) and further characterized. They were found to be of virulent pathotype (velogenic NDV) based on both pathogenicity assays (MDT, ICPI and IVPI) and partial F gene sequence analysis. Additionally, the phylogenetic analysis revealed that the isolates belonged to the genotype VIIi and XIII of class II avian Paramyxovirus serotype1 (APMV-1) and related closely to new emerging sub-genotypes. This is the first report regarding the presence of the fifth panzootic vNDV genotype VIIi from India. In this scenario, extensive epidemiological studies are suggested for surveillance of NDV genotypes in wild birds and poultry flocks of the country along with adopting suitable prevention and control measures.     

Effect of alcohol on viral hepatitis and other forms of liver dysfunction

Alcohol is a known hepatotoxic agent, which may exacerbate liver injury caused by other agents. The wide prevalence of alcohol use and abuse in society makes it an important cofactor in many other liver diseases. Examples of liver diseases that are significantly influenced by ingestion of alcohol include chronic viral hepatitis, disorders of iron overload, and obesity-related liver disease.     

Anchor residues in protein-protein interactions

We show that the mechanism for molecular recognition requires one of the interacting proteins, usually the smaller of the two, to anchor a specific side chain in a structurally constrained binding groove of the other protein, providing a steric constraint that helps to stabilize a native-like bound intermediate. We identify the anchor residues in 39 protein-protein complexes and verify that, even in the absence of their interacting partners, the anchor side chains are found in conformations similar to those observed in the bound complex. These ready-made recognition motifs correspond to surface side chains that bury the largest solvent-accessible surface area after forming the complex (> or =100 A2). The existence of such anchors implies that binding pathways can avoid kinetically costly structural rearrangements at the core of the binding interface, allowing for a relatively smooth recognition process. Once anchors are docked, an induced fit process further contributes to forming the final high-affinity complex. This later stage involves flexible (solvent-exposed) side chains that latch to the encounter complex in the periphery of the binding pocket. Our results suggest that the evolutionary conservation of anchor side chains applies to the actual structure that these residues assume before the encounter complex and not just to their loci. Implications for protein docking are also discussed.     

The use of echocardiographic indices in defining and assessing right ventricular systolic function in critical care research

Purpose

Many echocardiographic indices (or methods) for assessing right ventricular (RV) function are available, but each has its strengths and limitations. In some cases, there might be discordance between the indices. We conducted a systematic review to audit the echocardiographic RV assessments in critical care research to see if a consistent pattern existed. We specifically looked into the kind and number of RV indices used, and how RV dysfunction was defined in each study.

Methods

Studies conducted in critical care settings and reported echocardiographic RV function indices from 1997 to 2017 were searched systematically from three databases. Non-adult studies, case reports, reviews and secondary studies were excluded. These studies’ characteristics and RV indices reported were summarized.

Results

Out of 495 non-duplicated publications found, 81 studies were included in our systematic review. There has been an increasing trend of studying RV function by echocardiography since 2001, and most were conducted in ICU. Thirty-one studies use a single index, mostly TAPSE, to define RV dysfunction; 33 used composite indices and the combinations varied between studies. Seventeen studies did not define RV dysfunction. For those using composite indices, many did not explain their choices.

Conclusions

TAPSE seemed to be the most popular index in the last 2–3 years. Many studies used combinations of indices but, apart from cor pulmonale, we could not find a consistent pattern of RV assessment and definition of RV dysfunction amongst these studies.

     

Effect of glycemic control on the overnight dexamethasone suppression test in patients with diabetes mellitus.

Because many of the clinical features associated with Cushing's syndrome are frequently found in patients with diabetes mellitus, diabetic patients are often evaluated for Cushing's syndrome. The initial test for Cushing's syndrome is the 1 mg overnight dexamethasone suppression test (DST), but its value as a screening test in diabetic subjects, especially those with poor glycemic control, has been questioned. To address this issue, an overnight DST was administered to 100 subjects with diabetes. Only 7 patients failed to suppress their plasma cortisol to less than 140 nmol/L (5.0 micrograms/dL), achieving a specificity of 93%. There was no relation between acute glycemic control (as measured by the mean of 4 serum glucose values obtained before receiving dexamethasone) or chronic glycemic control (as measured by glycohemoglobin) and false positive responses to the 1 mg overnight DST. The mean of the measures of acute glycemic control of the 7 subjects who had false positive results, 14.4 +/- 2.8 mmol/L, was not significantly different than that of the 93 subjects with normal responses, 13.2 +/- 3.3 mmol/L. Similarly, the mean glycohemoglobin of the subjects with false positive results, 12.8 +/- 2.4%, was not significantly different than that of the subjects with normal responses, 12.9 +/- 2.5%. There was no correlation between plasma cortisol after dexamethasone and glycohemoglobin (r = 0.05), and only a weak correlation with the mean serum glucose (r = 0.21). We conclude that the 1 mg overnight DST is a valid screening test for Cushing's syndrome in patients with diabetes, regardless of glycemic control.     

New Insights into the Beneficial Electrophysiologic Profile of Ranolazine in Heart Failure: Prevention of Ventricular Fibrillation With Increased Postrepolarization Refractoriness and Without Drug-Induced Proarrhythmia

BackgroundRanolazine inhibits late Na⁺ and K⁺ currents. Earlier studies have reported an antiarrhythmic effect. The aim of the present study was to understand whether ranolazine could still preserve its antiarrhythmic properties in the settings of chronic heart failure (CHF).Methods and ResultsIn 12 female rabbits, CHF was induced by 4 weeks of rapid ventricular pacing leading to a decrease in ejection fraction. Twelve rabbits underwent sham operation. Isolated hearts were Langendorff perfused and demonstrated a significant QT prolongation after induction of heart failure. Ranolazine caused a concentration-dependent (10 and 30 μmol/L) increase of action potential duration (APD₉₀) in sham-operated and failing hearts. Eight endo- and epicardial monophasic action potentials revealed a nonsignificant increase in spatial and temporal dispersion of repolarization. The increase in APD₉₀ was accompanied by a greater increase in refractory period, resulting in a significant increase in postrepolarization refractoriness in sham-operated (+29 ms and +55 ms; P < .01) and failing (+22 ms and +30 ms; P < .05) hearts. In control conditions, programmed ventricular stimulation and a burst pacing protocol led to ventricular fibrillation (VF) in 5 of the 12 sham-operated (6 episodes) and in 7 of the 12 failing (18 episodes) hearts. In the presence of ranolazine, VF was inducible in only 2 of 12 failing hearts (5 episodes). In the presence of low [K⁺], only 1 ranolazine-treated sham-operated heart developed early afterdepolarizations and ventricular tachyarrhythmias despite significant QT prolongation.ConclusionsRanolazine decreases inducibility of VF in the presence of a significant increase in postrepolarization refractoriness. This antiarrhythmic effect in the intact heart is preserved in CHF and is not associated with drug-induced proarrhythmia.     

Leber hereditary optic neuropathy—new insights and old challenges

Graefe's Archive for Clinical and Experimental Ophthalmology - Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial DNA (mtDNA) disorder with the majority of...     

Early use of MRI improves diagnostic accuracy in young adults with stroke

ObjectivesThe misdiagnosis of acute ischemic stroke in young adults is a significant problem since patients may have many decades of potential disability. Also, proven therapies for acute stroke may not be administered if there is an initial misdiagnosis. We assessed the hypothesis that early use of MRI, arrival by ambulance, and presentation to a Primary Stroke Center (PSC) would be associated with a reduced rate of misdiagnosis.MethodsA prospective database of young adults (ages 16–49 years) with ischemic stroke (final diagnosis provided by vascular neurologists) was reviewed. We collected information on several variables, including age, race, arrival by ambulance, whether brain MRI was performed within 48 h, and initial presentation to a PSC. Variables were tested against emergency department (ED) misdiagnosis using univariate and multivariate methods.Results77 patients with a mean age of 37.9 years were reviewed. 48.3% of patients arrived by ambulance, 53.2% had a brain MRI within 48 h, and 23.4% initially presented to a PSC. The overall rate of ED misdiagnosis was 14.5%. In multivariate testing, performance of MRI within 48 h (p = 0.023) was associated with a lower rate of misdiagnosis and age < 35 years was linked with greater likelihood of misdiagnosis (p = 0.047).ConclusionsEarly performance of MRI leads to greater accuracy of stroke diagnosis in young adults presenting to the ED. Patients less than age 35 years have a greater risk of misdiagnosis. ED physicians and neurologists should consider early use of MRI in young adults with stroke-like deficits and diagnostic uncertainty.