Correlation of Hepatic Venous Pressure Gradient Level With Clinical and Endoscopic Parameters in Decompensated Chronic Liver Disease.

BACKGROUND: The amount of liver fibrosis usually correlates with portal pressure, which is measured as the hepatic venous pressure gradient (HVPG). The fact that portal pressure significantly decreases after treatment may increase cirrhotic patients' long-term survival suggests that measuring HVPG may offer specific information for outcome prediction. The study thus seeks to determine the relationship between the level of the HVPG and endoscopic and clinical parameters in decompensated chronic liver disease (CLD). METHODOLOGY: Thirty patients with CLD were studied and subjected to serum creatinine, total bilirubin, serum sodium, serum albumin, prothrombin time (PT), international normalized ratio (INR), esophagogastroduodenoscopy (upper gastrointestinal (UGI) endoscopy), and transjugular or transfemoral catheterization for HVPG measurement, and Child-Turcotte-Pugh (CTP) score and Model for End-Stage Liver Disease (MELD) score were calculated. RESULTS: The results indicates a strong positive connection between MELD and HVPG, which is statistically significant (r=0.754; p<0.001). Similarly, CTP and HVPG also exhibit a significant positive association (r=0.793; p<0.001) suggesting a link between the severity of liver disease. Additionally, the moderate positive correlation for encephalopathy has a significant value (r=0.584; p=0.001), while the weak positive correlations for serum bilirubin, INR, and HVPG have non-significant values (r=0.244; p=0.194, and r=0.375; p=0.041, respectively). A strong negative connection between serum albumin and HVPG was also found (r=0.546; p=0.005) suggesting a relationship between worsening liver function. CONCLUSION: In patients with decompensated CLD, the severity of the CLD as measured by the CTP and MELD score corresponds with HVPG, and higher HVPG associated with severe CLD and severe ascites, large varices, and variceal hemorrhage. Higher HVPG in cirrhotic patients also suggests the existence of sequelae, such as varices, severe ascites, and severe hepatic encephalopathy, although HVPG has little bearing on the underlying cause.

Physical, Electrochemical, and Solvent Permeation Properties of Amphiphilic Conetwork Membranes Formed through Interlinking of Poly(vinylidene fluoride)-Graft-Poly[(2-dimethylamino)ethyl Methacrylate] with Telechelic Poly(ethylene glycol) and Small Molecular Weight Cross-Linkers.

We report the preparation of dense and porous amphiphilic conetwork (APCN) membranes through the covalent interconnection of poly(vinylidene fluoride)-graft-poly[(2-dimethylamino)ethyl methacrylate] (PVDF-g-PDMAEMA) copolymers with telechelic poly(ethylene glycol) (PEG) or α,α-dichloro-p-xylene (XDC). The dense APCN membranes exhibit varying solvent swelling and mechanical properties depending on the compositions and overall crystallinity. The crystallinity of both PVDF (20-47%) and PEG (9-17%) is significantly suppressed in the dense APCNs prepared through the interconnection of PVDF-g-PDMAEMA with reactive PEG as compared to the APCN membranes (48-53%) prepared with XDC as well as mechanical blend of PVDF-g-PDMAEMA plus nonreactive PEG. The dense APCN membranes exhibit a good transport number of monovalent ions and ionic conductivity. The APCN membrane interconnected with PEG and containing binary ionic liquids exhibits a room-temperature lithium ion conductivity of 0.52 mS/cm. On the other hand, APCN ultrafiltration (UF) membranes exhibit organic solvent-resistant behavior. The UF membrane obtained by interconnecting PVDF-g-PDMAEMA with telechelic PEG shows low protein fouling propensity, higher hydrophilicity, and water flux as compared to membranes prepared using XDC as the interconnecting agent. The significant effect of the covalent interconnection of the amphiphilic graft copolymers with telechelic PEG or XDC on the overall properties provides a good opportunity to modulate the properties and performance of APCN membranes.

Airborne Lidar Measurements of XCO2 in Synoptically Active Environment and Associated Comparisons With Numerical Simulations.

Frontal boundaries have been shown to cause large changes in CO2 mole-fractions, but clouds and the complex vertical structure of fronts make these gradients difficult to observe. It remains unclear how the column average CO2 dry air mole-fraction (XCO2) changes spatially across fronts, and how well airborne lidar observations, data assimilation systems, and numerical models without assimilation capture XCO2 frontal contrasts (ΔXCO2, i.e., warm minus cold sector average of XCO2). We demonstrated the potential of airborne Multifunctional Fiber Laser Lidar (MFLL) measurements in heterogeneous weather conditions (i.e., frontal environment) to investigate the ΔXCO2 during four seasonal field campaigns of the Atmospheric Carbon and Transport-America (ACT-America) mission. Most frontal cases in summer (winter) reveal higher (lower) XCO2 in the warm (cold) sector than in the cold (warm) sector. During the transitional seasons (spring and fall), no clear signal in ΔXCO2 was observed. Intercomparison among the MFLL, assimilated fields from NASA's Global Modeling and Assimilation Office (GMAO), and simulations from the Weather Research and Forecasting--Chemistry (WRF-Chem) showed that (a) all products had a similar sign of ΔXCO2 though with different levels of agreement in ΔXCO2 magnitudes among seasons; (b) ΔXCO2 in summer decreases with altitude; and (c) significant challenges remain in observing and simulating XCO2 frontal contrasts. A linear regression analyses between ΔXCO2 for MFLL versus GMAO, and MFLL versus WRF-Chem for summer-2016 cases yielded a correlation coefficient of 0.95 and 0.88, respectively. The reported ΔXCO2 variability among four seasons provide guidance to the spatial structures of XCO2 transport errors in models and satellite measurements of XCO2 in synoptically-active weather systems.

Opportunistic experiments to constrain aerosol effective radiative forcing.

Aerosol-cloud interactions (ACIs) are considered to be the most uncertain driver of present-day radiative forcing due to human activities. The nonlinearity of cloud-state changes to aerosol perturbations make it challenging to attribute causality in observed relationships of aerosol radiative forcing. Using correlations to infer causality can be challenging when meteorological variability also drives both aerosol and cloud changes independently. Natural and anthropogenic aerosol perturbations from well-defined sources provide "opportunistic experiments" (also known as natural experiments) to investigate ACI in cases where causality may be more confidently inferred. These perturbations cover a wide range of locations and spatiotemporal scales, including point sources such as volcanic eruptions or industrial sources, plumes from biomass burning or forest fires, and tracks from individual ships or shipping corridors. We review the different experimental conditions and conduct a synthesis of the available satellite datasets and field campaigns to place these opportunistic experiments on a common footing, facilitating new insights and a clearer understanding of key uncertainties in aerosol radiative forcing. Cloud albedo perturbations are strongly sensitive to background meteorological conditions. Strong liquid water path increases due to aerosol perturbations are largely ruled out by averaging across experiments. Opportunistic experiments have significantly improved process-level understanding of ACI, but it remains unclear how reliably the relationships found can be scaled to the global level, thus demonstrating a need for deeper investigation in order to improve assessments of aerosol radiative forcing and climate change.

Identification of GBA mutations among neurodegenerative disease patients from eastern India.

INTRODUCTION: GBA mutations have been reported in PD, PDD and DLB - but not associated with cognitive impairment for example in PSP, AD or MSA. However, frequencies of GBA mutations are ethnicity dependent. The present study aims to identify commonly reported GBA mutations (mostly from Asia), among eastern Indian patients with neurodegenerative disorders. METHODS: The patient cohort consisting of 198 classical PD cases, 136 PD cases with cognitive impairment, 184 cases with Parkinson Plus syndrome, 46 AD and 241 unrelated controls, from eastern India. Subjects were analyzed for IVS2 + 1A > G, p.Arg120Trp, p.His255Gln, p.Arg257Gln, p.Glu326Lys, p.Asn370Ser, p.Asp409His, p.Leu444Pro, & RecNciI by PCR-RFLP techniques and confirmed by Sanger sequencing method. RESULTS: We have identified only p.Leu444Pro variant among nine cases; three PDD, one DLB, two PD, two PSP and one AD patients in heterozygous condition. The highest frequency for p.Leu444Pro variant was found among PDD subgroup (3.95 %, P = 0.0134). An overall significant overrepresentation of positive family history (P = 0.000049), impaired recent memory (P = 0.0123) was observed among p.Leu444Pro carriers. Further, subgroup analysis for PD, PD-MCI and PDD, revealed statistically significant higher frequency of early age at onset (P = 0.0455), positive family history (P = 0.0025), higher UPDRS III score (off state) (P = 0.006), advanced H&Y stage (P = 0.045) and anxious behaviour (P = 0.0124) among p.Leu444Pro positive patients. CONCLUSION: The p.Leu444Pro mutation of GBA was found in patients with PD, PDD, DLB, PSP and AD. An Overall higher frequency of positive family history and impaired recent memory are significantly associated with for p.Leu444Pro carriers from eastern India. Our study also ascertains contribution of p.Leu444Pro to an earlier onset of PD, PD-MCI and PDD, higher UPDRS III score (off state) against positive family history background. Furthermore, taking into consideration other Indian studies, we can conclude that p.Leu444Pro mutation plays a limited role in PD and other neurodegenerative disorders.

Association of APOE Gene Polymorphism with Stroke Patients from Rural Eastern India.

CONTEXT: Studies from the different ethnic regions of the world have reported variable results on association of APOE gene polymorphism in stroke. AIM: The aim of this study is to find out the possible association of APOE polymorphism in stroke patients in ethnic Bengali population. SETTINGS AND DESIGN: A prospective case-control study was undertaken in the Department of Neurology, Burdwan Medical College, Burdwan, West Bengal, India, over a period of 3 years. METHODS: We collected 10 ml venous blood samples from 148 clinically and radiologically diagnosed acute stroke patients (80 of ischemic stroke and 68 of intracerebral hemorrhage) and consecutive 108 ethnic age- and sex-matched controls, in ethylenediaminetetraacetic acid vials after informed written consent. Genomic DNA was prepared at S.N. Pradhan Centre of Neurosciences, University of Calcutta, Kolkata, India. Exotic single-nucleotide polymorphisms (rs429358, rs 7412) were analyzed by polymerase chain reaction-restriction fragment length polymorphism for genotype of APOE. RESULTS: The frequencies of different APOE allele among 80 ischemic stroke patients were 5.6% (n = 9) for E2, 75.68% (n = 121) for E3, and 18.7% (n = 30) for E4. The E3 allele is significantly over-represented (P = 0.004) in controls compared to the patients (88% in controls vs 75.6% ischemic stroke patients and 80% hemorrhagic patients). A significantly high frequency of APOE4 allele was observed in ischemic (18.7%) and hemorrhagic patients (11%) compared to controls (8%). The E4 allele plays a major risk for developing ischemic stroke [odds ratio (OR) = 2.744; 95% confidence interval (CI): 1.43-5.10] and E3 plays a protective role for hemorrhagic stroke (OR = 0.53; 95% CI: 0.29-0.96), while E4 allele plays a nonsignificant (P = 0.31) increase in trend in hemorrhage stroke (OR = 1.4). CONCLUSIONS: There is significant association of APOE gene polymorphism in stroke patients of ethnic Bengali population. The E4 allele increases significant risk for development of ischemic strokes, and it also plays nonsignificant increase in trend in hemorrhagic strokes.

Pattern of cognitive deficits in vascular dementia.

Background & objectives: There is a paucity of literature on the cognitive profiles of vascular dementia (VaD) in India. The current study was undertaken to investigate the pattern of cognitive deficits in patients with VaD. Methods: Fifty patients fulfilling the Diagnostic and Statistical Manual of Mental Disorders-IV criteria of dementia and National Institute of Neurological Disorders and Stroke - Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria for VaD were assessed using Mini Mental State Examination, Kolkata Cognitive Screening Battery and other relevant tests including magnetic resonance imaging of brain. Results: Twenty patients had small vessel dementia, whereas the least common was haemorrhagic dementia in four patients. In patients with small vessel dementia, apart from memory, all patients had problem in attention and executive function, whereas 12 patients had visuoconstructional deficit and eight patients had language problem. In a total of 12 patients with large vessel dementia, apart from memory, executive dysfunction and visuoconstructional deficit were noted in 10 patients, whereas attention deficit was noted in eight patients. Attention was found to be more involved in small-vessel dementia than large-vessel dementia though all had memory impairment (P<0.01). Interpretation & conclusions: Small vessel dementia was the commonest subtype of VaD in our study. Memory, attention and executive functions were predominantly affected in patients with VaD. Attention was significantly more involved in small vessel dementia than large vessel dementia. Further studies with large sample size need to be done in different regions of the country.

Storage, Degradation, and New Connectivity of Face-Related Semantic Memory in Alzheimer's Disease.

BACKGROUND: Excepting amnesia, impairment of other domains also hampers the activity of daily living in Alzheimer's disease (AD). Although prosopagnosia poses problem in interacting with other persons, it rarely causes problem during interaction with close relatives as known voice acts as cue for recognition. OBJECTIVE: In a cohort of AD, we planned to study errors in recognition, naming, and assigning relationship of close relatives, to assess the type and frequency of errors and to explain with current knowledge and hypothesis. MATERIALS AND METHODS: This cross-sectional study was conducted in Memory Clinic of Medical College Hospital, Kolkata, India, between July 2013 and June 2015. Patients were evaluated by history, general neurological examination, and neuropsychological tests. A structured questionnaire was used to assess recognition (use of honorifics) and naming defect of close relatives. RESULTS: AD was diagnosed in 42 patients. Prosopagnosia was found in 14 and anomia in 6 patients. Four patients exhibited problem during conversation with close relatives. They assigned name and relation of one generation earlier to close relatives with proper recognitions. DISCUSSION: We got predictive error of name and relation assignment of close relatives by one generation back with normal recognition. It can be explained by two memory traces in connection of face-visual and name (with/without relation) representation, earlier being hierarchically older and more resistant to wearing. CONCLUSIONS: We hypothesize that the name/relation store is orderly conserved. In AD, after degradation of part of name/relation store, a new wiring might be built up between these two traces.

Pattern of Idiopathic Intracranial Hypertension in Indian Population.

OBJECTIVE: To evaluate the clinical and demographic profile, laboratory parameters and outcomes of Idiopathic Intracranial hypertension (IIH) patients from Indian subpopulation. MATERIALS AND METHOD: We did a prospective study on patients who fulfilled the revised diagnostic criteria for Primary pseudotumor cerebri syndrome in adults and children, proposed by Friedman et al in 2013. All patients were examined for BMI, papilloedema, extraocular muscle movement, opening CSF pressure and underwent MRI, MR venography of brain and perimetry. Patients were followed up for a minimum period of 6 months, upto 2 years, with the outcomes monitored being visual acuity, visual field, headache, diplopia and optic disc changes. RESULTS: We evaluated 33 patients (31 female and 2 male). 25 patients had BMI less than 25. Commonest clinical presentation was headache. 7 patients showed normal CSF opening pressure. The most common MRI finding was flattening of posterior aspect of globe and was found in 90.90% (30). 25 patients showed either unilateral or bilateral transverse sinus stenosis. Most common finding in perimetry was enlarged blind spot. 4 patients recovered spontaneously and rests were treated with acetazolamide (1gm/day). All showed favorable outcome when followed up. CONCLUSION: Obesity may not be a dominant risk factor for development of IIH in the Indian subcontinent. Non obese IIH have better prognosis and tend to have a good response to medical management alone.

Optical Coherence Tomography Findings in Patients of Parkinson's Disease: An Indian Perspective.

BACKGROUND: Parkinson's disease (PD) is one of the most common neurodegenerative movement disorders and its incidence is increasing worldwide along with population aging. Previous clinical and histologic studies suggest that the neurodegenerative process, which affects the brain, may also affect the retina of PD patients. OBJECTIVE: The objective of this study was to determine the thickness changes of retina nerve fibers and macular volume with optical coherence tomography (OCT) in PD patients. MATERIALS AND METHODS: The spectral domain OCT was used to assess the thickness of retinal nerve fiber layer (RNFL) and macular volume from 34 PD patients and 50 healthy age-matched controls. RESULTS: Compared with healthy age-matched controls, the RNFL thickness of PD patients was much thinner (P < 0.05) in all retinal quadrants, with temporal thinning being more than nasal thinning. Macular volumes were diminished in both perifoveal and outer macular regions in all sectors (P < 0.05) with preserved foveal volume. The degree of tissue loss corroborated with the severity of disease as objectively assessed by standardized rating scales (UPDRS). CONCLUSION: There is generalized retinal nerve degeneration in patients of PD and the degree of loss correlated with the severity and duration of disease.

Solvent effect in the synthesis of hydrophobic drug-loaded polymer nanoparticles.

Quercetin is an abundant flavonoid in fruits, vegetables such as onion, tea leaves, cranberry, radish leaves etc. with numerous biological activities and widely used as an effective antioxidant. Its low solubility in water and chemical decomposition in intestinal environment are predicaments in delivery through dietary or oral intake. Noble polymeric nanoparticles are of particular interest today because of their applications in many areas. Polymer nanoparticles have attracted the interest of many research groups and have been utilised in an increasing number of fields such as site targeted drug delivery in cancer research during the last decades. Various techniques can be used to produce polymer nanoparticles, such as solvent evaporation, salting-out, dialysis, supercritical fluid technology etc. The choice of method depends on a number of factors, such as, particle size, particle size distribution, area of application, etc. In the present study, single emulsion-solvent evaporation technique has been utilised with two different organic solvents: acetone and chloroform/methanol to prepare quercetin loaded poly(D,L-lactide-co-glycolide) nanoparticles. According to the authors' observations acetone is a better solvent for encapsulating quercetin in polymer nanoparticles owing to its physical and chemical properties.

Development of Bengali Audio-Visual Test Battery for Assessment of Pragmatic Skills: Preliminary Normative Data Based on Educational Level.

Pragmatic competence may be disrupted due to psychological and neurological causes. For appropriate remedy and rehabilitation, a precise assessment of pragmatic skills is important. However, there is no test battery in the Bengali language, and consequently, there is no published data on pragmatic ability of Bengali speakers. Due to the vast diversity of the population, it becomes increasingly difficult to assess pragmatic ability of an individual without a proper knowledge of the normal variations. To address this problem we have developed a test battery in Bengali, and to begin with, we have administered it to one hundred and five (105) normal healthy persons having different levels of education. The four groups having 17 years and above, 15 to < 17 years, 12 to < 15 years and 10 to < 12 years of education yielded a normative score of 193, 189, 171 and 150, respectively. These normative scores will allow clinicians to make a proper assessment of patients suffering from pragmatic deficits and help avoid interpreting social differences as neurological deficits.

Anthracycline Drugs on Modified Surface of Quercetin-Loaded Polymer Nanoparticles: A Dual Drug Delivery Model for Cancer Treatment.

Polymer nanoparticles are vehicles used for delivery of hydrophobic anti-cancer drugs, like doxorubicin, paclitaxel or chemopreventors like quercetin (Q). The present study deals with the synthesis and characterisation of nano formulations (NFs) from Q loaded PLGA (poly lactic-co-glycolic acid) nano particles (NPs) by surface modification. The surface of Q-loaded (NPs) is modified by coating with biopolymers like bovine serum albumin (BSA) or histones (His). Conventional chemotherapeutic drugs adriamycin (ADR) and mitoxantrone (MTX) are bound to BSA and His respectively before being coated on Q-loaded NPs to nano formulate NF1 and NF2 respectively. The sizes of these NFs are in the range 400-500 nm as ascertained by SEM and DLS measurements. Encapsulation of Q in polymer NPs is confirmed from shifts in FT-IR, TGA and DSC traces of Q-loaded NPs compared to native PLGA and Q. Surface modification in NFs is evidenced by three distinct regions in their TEM images; the core, polymer capsule and the coated surface. Negative zeta potential of Q-loaded NPs shifted to positive potential on surface modification in NF1 and NF2. In vitro release of Q from the NFs lasted up to twenty days with an early burst release. NF2 is better formulation than NF1 as loading of MTX is 85% compared to 23% loading of ADR. Such NFs are expected to overcome multi-drug resistance (MDR) by reaching and treating the target cancerous cells by virtue of size, charge and retention.

On the factors governing water vapor turbulence mixing in the convective boundary layer over land: Concept and data analysis technique using ground-based lidar measurements.

The convective boundary layer (CBL) turbulence is the key process for exchanging heat, momentum, moisture and trace gases between the earth's surface and the lower part of the troposphere. The turbulence parameterization of the CBL is a challenging but important component in numerical models. In particular, correct estimation of CBL turbulence features, parameterization, and the determination of the contribution of eddy diffusivity are important for simulating convection initiation, and the dispersion of health hazardous air pollutants and Greenhouse gases. In general, measurements of higher-order moments of water vapor mixing ratio (q) variability yield unique estimates of turbulence in the CBL. Using the high-resolution lidar-derived profiles of q variance, third-order moment, and skewness and analyzing concurrent profiles of vertical velocity, potential temperature, horizontal wind and time series of near-surface measurements of surface flux and meteorological parameters, a conceptual framework based on bottom up approach is proposed here for the first time for a robust characterization of the turbulent structure of CBL over land so that our understanding on the processes governing CBL q turbulence could be improved. Finally, principal component analyses will be applied on the lidar-derived long-term data sets of q turbulence statistics to identify the meteorological factors and the dominant physical mechanisms governing the CBL turbulence features.

Clinicopathological profile and management of severe autoimmune hepatitis.

BACKGROUND: Severe autoimmune hepatitis is an entity which has been rarely reported in the Indian literature. We describe here the clinicopathological profile and treatment of severe autoimmune hepatitis (SAH) which is to the best of our knowledge the first report from India addressing this illness. METHODS AND RESULTS: Between September 2010 and March 2013, 13 patients seeking treatment at our centre were diagnosed as SAH and treated with steroids. Jaundice along with coagulopathy was the presenting symptom in all these patients. Ascites was present in ten and encephalopathy in 6 patients. The median serum IgG was 2135 mg/dl (range: 1122-5490).Significant titers of autoantibodies were present in all patients except one. Transjugular liver biopsy in 9 patients showed characteristic features of SAH such as extensive bridging necrosis and moderate to dense portal inflammation. With corticosteroid therapy, 10 patients survived while three died. In those who survived, biochemical improvement was seen as early as seven days with excellent long-term remission. CONCLUSIONS: Clinical suspicion supported by liver biopsy and autoimmune serology led to the diagnosis of SAH in a cohort of patients with unexplained liver failure. Corticosteroids were beneficial in majority of patients affording excellent results and this could be predicted by early reduction in serum bilirubin within 7-15 days.

Inhibition of catalase by tea catechins in free and cellular state: a biophysical approach.

Tea flavonoids bind to variety of enzymes and inhibit their activities. In the present study, binding and inhibition of catalase activity by catechins with respect to their structure-affinity relationship has been elucidated. Fluorimetrically determined binding constants for (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG) with catalase were observed to be 2.27×106 M(-1) and 1.66×106 M(-1), respectively. Thermodynamic parameters evidence exothermic and spontaneous interaction between catechins and catalase. Major forces of interaction are suggested to be through hydrogen bonding along with electrostatic contributions and conformational changes. Distinct loss of α-helical structure of catalase by interaction with EGCG was captured in circular dichroism (CD) spectra. Gallated catechins demonstrated higher binding constants and inhibition efficacy than non-gallated catechins. EGCG exhibited maximum inhibition of pure catalase. It also inhibited cellular catalase in K562 cancer cells with significant increase in cellular ROS and suppression of cell viability (IC50 54.5 µM). These results decipher the molecular mechanism by which tea catechins interact with catalase and highlight the potential of gallated catechin like EGCG as an anticancer drug. EGCG may have other non-specific targets in the cell, but its anticancer property is mainly defined by ROS accumulation due to catalase inhibition.

Acute pancreatitis and hyperparathyroidism: a case series.

Primary hyperparathyroidism is a rare cause of acute pancreatitis. Five consecutive patients with acute or recurrent acute pancreatitis and primary hyperparathyroidism were included. All patients had elevated serum calcium on admission and high levels of circulating parathyroid hormone. Both ultrasonography and Sestamibi scan was used to localize parathyroid adenoma. Except for one, all patients underwent parathyroidectomy and postoperative histology was consistent with parathyroid adenoma. One patient died while on treatment. Metabolic causes of acute pancreatitits, though uncommon, are important as early recognition helps management and prevents recurrence.