Response evaluation of locoregional therapies in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma versus hepatocellular carcinoma: a propensity score matched study.

AIM: To evaluate the response of locoregional therapy (LRT) on combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (IHC) and compare their outcomes with propensity matched hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: From January 2011 to July 2020, 13 patients with cHCC-CC (11 men, two women, median age 56 years) and 15 IHC patients (10 men, five women, median age 60 years) were compared with 101 HCC patients (79 men, 22 women, median age 60 years) after LRT. All tumours were proven histologically. Among the 13 cHCC-CC patients, 11 received transarterial chemoembolisation (TACE), one received microwave ablation (MWA) and one received TACE with radiofrequency ablation (RFA). Of 15 IHC patients, eight received TACE, five received RFA, and one received MWA, and one received TACE with RFA. Propensity score matching (PSM) was done with conditional logistic regression adjusted for age, type of LRT, tumour specific features and Child-Pugh score. RESULTS: After LRT, on univariate analysis an objective response was seen in 30% of cHCC-CC and 53% of IHC patients. PSM analysis demonstrated shorter progression-free survival (PFS; cHCC-CC versus HCC: 1.5 versus 7.5 months; IHC versus HCC: 6 versus 14 months, p<0.05), overall survival (OS; cHCC-CC versus HCC: 12 versus 28 months; IHC versus HCC: 18 versus 34 months, p<0.005), and poor objective response (cHCC-CC versus HCC: 25% versus 91%; IHC versus HCC: 58% versus 88%, p<0.05) in cHCC-CC and IHC patients versus HCC patients. Hypovascular tumour, macrovascular invasion, and infiltrative appearance were independent prognostic factors for OS in IHC patients. CONCLUSION: cHCC-CC and IHC are aggressive tumours with a poor objective response, greater distant progression of the disease and shorter PFS and OS post LRT as compared to HCC.

Self-assembled structure and dynamics of imidazolium-based protic salts in water solution.

Protic ionic liquids containing cations with long alkyl chains can form self-assembled micelles, vesicles, microemulsions, and lyotropic liquid crystal structures in water, acid water or tetrahydrofuran, etc. As a result of this unique property, they are regarded as a novel category of amphiphiles, and are gaining importance in the field of colloid and interface chemistry. The critical micelle concentration (CMC) of protic salts, e.g., alkyl-ammonium nitrates in water, was found to increase with decreasing chain length. It is generally believed that a long alkyl chain length is essential for the formation of self-assembled structures. So far, no self-assembled structure has been reported for protic ionic liquids with an alkyl chain length of n < 4. This paper reports on the structure and dynamics of two imidazolium based protic organic salts with no alkyl chain or a methyl group (n = 1) attached to the cation in water solution, determined through a detailed analysis of NMR spectra and pulsed-field gradient NMR data. We demonstrate that these imidazolium cations with no or a short alkyl chain (n = 1) can form a self-assembled clustering structure in water solution, which has a strong influence on the diffusion behavior of imidazolium molecular ions. It is speculated that this self-assembled structure is likely to be present in other similar solutions of ionic liquids with short alkyl chains.

Targeted methylation sequencing of plasma cell-free DNA for cancer detection and classification.

Background: Targeted methylation sequencing of plasma cell-free DNA (cfDNA) has a potential to expand liquid biopsies to patients with tumors without detectable oncogenic alterations, which can be potentially useful in early diagnosis. Patients and methods: We developed a comprehensive methylation sequencing assay targeting 9223 CpG sites consistently hypermethylated according to The Cancer Genome Atlas. Next, we carried out a clinical validation of our method using plasma cfDNA samples from 78 patients with advanced colorectal cancer, non-small-cell lung cancer (NSCLC), breast cancer or melanoma and compared results with patients' outcomes. Results: Median methylation scores in plasma cfDNA samples from patients on therapy were lower than from patients off therapy (4.74 versus 85.29; P = 0.001). Of 68 plasma samples from patients off therapy, methylation scores detected the presence of cancer in 57 (83.8%), and methylation-based signatures accurately classified the underlying cancer type in 45 (78.9%) of these. Methylation scores were most accurate in detecting colorectal cancer (96.3%), followed by breast cancer (91.7%), melanoma (81.8%) and NSCLC (61.1%), and most accurate in classifying the underlying cancer type in colorectal cancer (88.5%), followed by NSCLC (81.8%), breast cancer (72.7%) and melanoma (55.6%). Low methylation scores versus high were associated with longer survival (10.4 versus 4.4 months, P < 0.001) and longer time-to-treatment failure (2.8 versus 1.6 months, P = 0.016). Conclusions: Comprehensive targeted methylation sequencing of 9223 CpG sites in plasma cfDNA from patients with common advanced cancers detects the presence of cancer and underlying cancer type with high accuracy. Methylation scores in plasma cfDNA correspond with treatment outcomes.

The influence of anion chemistry on the ionic conductivity and molecular dynamics in protic organic ionic plastic crystals.

Proton conductors are widely used in different electrochemical devices including fuel cells and redox flow batteries. Compared to conventional proton conducting polymer membranes, protic organic ionic plastic crystal (POIPC) is a novel solid-state proton conductor with high proton conductivity even under anhydrous conditions. In this work, different organic protic salts based on the same parent di-functional cation with different anions were synthesized and characterized. It is found that the di-protonated cation plays an important role in defining the thermal properties, leading to stronger plastic crystal behavior and a higher melting point. Static solid-state NMR and the synchrotron XRD results show that the di-protonated cation allows greater dynamics in the crystal in contrast to the mono-protonated counterparts. The 1-(N,N-dimethylammonium)-2-(ammonium)ethane triflate ([DMEDAH2][Tf]2) has the highest ionic conductivity of 1.1 × 10-4 S cm-1 at 50 °C, whereas the bis(trifluoromethanesulfonyl)amide counterpart [DMEDAH2][TFSA]2 has the lowest ionic conductivity (2.8 × 10-7 S cm-1 at 50 °C) with no measureable mobile ion component at this temperature. The fraction of mobile species is significantly suppressed in the TFSA containing salts as against the Tf systems.

Acute inhalation toxicity study of n-heneicosane and its combination with diflubenzuron: An attracticide of Aedes aegypti.

OBJECTIVE: Combination of an oviposition pheromone and an insect growth regulator for the control of vectors is an effective approach. There is a need for toxicological evaluation before its introduction. The present study evaluates the acute inhalation toxicity of n-heneicosane and its combination with diflubenzuron in a head-only inhalation exposure chamber made of glass. MATERIALS AND METHODS: A head-only inhalation exposure chamber made of glass (volume: 3.5 l) was used for exposing four rats at a time. A glass nebulizer was used for aerosolization of n-heneicosane and its combination with diflubenzuron (1:10 w/w). Nebulization pressure was 10 and 15 psi and the air flow of exposure the chamber was adjusted to 30 lpm. Male Wistar rats were acclimatized in whole body plethysmographs that were connected to volumetric flow pressure transducers by silicon tubes. The transducers were connected to an amplifier and a digitized response was recorded through an oscillograph and personal computers. Respiratory variables were recorded online. After inhalation exposure, various other parameters like survival, body weight, organ body weight index and biochemical changes were recorded for analysis. RESULTS AND DISCUSSION: Particle size determination proved that the aerosol particles were within the respirable range. LC50 of n-heneicosane and its combination with diflubenzuron was found to be more than 5 g/m3. There were minimal changes observed during exposure to n-heneicosane and also its combination with diflubenzuron on the respiratory variables. The changes were not consistent with the dose. CONCLUSION: n-Heneicosane and its combination with diflubenzuron showed low mammalian toxicity.

Protein loosing enteropathy after Fontan procedure.

Fontan and Baudet described the procedure in 1971 and was very useful to improve the quality of life in many complex cyanotic heart diseases. It has gone through various modifications since then to improve the outcome. The mortality was reported as 2.1% and survival rate of at 5 years, 10 years, 15 years and 20 years were 91%, 80%, 73%and 69% respectively. Though it was a useful palliative procedure to improve the quality of life, it has complications which may affect the morbidity and mortality like Protein loosing enteropathy ,reduced exercise capacity thromboembolism. The patients with protein losing enteropathy present with Pleural effusion, ascites, and edema and they need periodic replacement of Albumin and frequent reviews and close follow up in the management to reduce the mortality and to improve the quality of life .These complications we come across and they need our support in the management at district level hospitals.

New dimensions in salt-solvent mixtures: a 4th evolution of ionic liquids.

In the field of ionic liquids (ILs) it has long been of fundamental interest to examine the transition from salt-in-solvent behaviour to pure liquid-salt behaviour, in terms of structures and properties. At the same time, a variety of applications have beneficially employed IL-solvent mixtures as media that offer an optimal set of properties. Their properties in many cases can be other than as expected on the basis of simple mixing concepts. Instead, they can reflect the distinct structural and interaction changes that occur as the mixture passes through the various stages from pure coulombic medium, to "plasticised" coulombic medium, into a meso-region where distinct molecular and ionic domains can co-exist. Such domains can persist to quite a high dilution into the salt-in-solvent regime and their presence manifests itself in a number of important synergistic interaction effects in diverse areas such as membrane transport and corrosion protection. Similarly, the use of ionic liquids in synthetic processes where there is a significant volume fraction of molecular species present can produce a variety of distinct and unexpected effects. The range of these salt-solvent mixtures is considerably broader than just those based on ionic liquids, since there is only minor value in the pure salt being a liquid at the outset. In other words, the extensive families of organic and metal salts become candidates for study and use. Our perspective then is of an evolution of ionic liquids into a broader field of fundamental phenomena and applications. This can draw on an even larger family of tuneable salts that exhibit an exciting combination of properties when mixed with molecular liquids.

Mechanisms of low temperature capture and regeneration of CO2 using diamino protic ionic liquids.

Carbon dioxide (CO2) chemical absorption and regeneration was investigated in two diamino carboxylate protic ionic liquids (PILs), dimethylethylenediamine formate (DMEDAH formate) and dimethylpropylenediamine acetate (DMPDAH acetate), using novel calorimetric techniques. The PILs under study have previously been shown to possess a CO2 absorption capacity similar to the industrial standard, 30% aqueous MEA, while requiring much lower temperatures to release the captured CO2. We show that this is in part due to the fact that the PILs exhibit enthalpies of CO2 desorption as low as 40 kJ mol(-1), significantly lower than the 85 kJ mol(-1) required for 30% aqueous MEA. Computational and spectroscopic analyses were used to probe the mechanism of CO2 capture, which was found to proceed via the formation of carbamate moieties on the primary amine of both DMEDAH and DMPDAH. Evidence was also found that weakly acidic counter-ions such as formate and acetate provide, unexpectedly, an additional proton acceptor site in the traditional carbamate mechanism, revealing opportunities to increase CO2 uptake capacity in the future through careful design of the anion and cation used in the PIL capture agent.

Control of Aedes aegypti and Ae. albopictus, the vectors of dengue and chikungunya, by using pheromone C21 with an insect growth regulator: Results of multicentric trials from 2007-12 in India.

BACKGROUND & OBJECTIVES: Aedes mosquito control has gained much importance nowadays in view of rise in number of reported cases of dengue and chikungunya in India and other countries. In the present study, C21 attracticide (containing a pheromone and an insect growth regulator­IGR, developed by Defence Research and Development Establishment (DRDE), Gwalior, India was tested for its feasibility for surveillance and control of Aedes mosquito in a multicentric mode from October 2007 to June 2012 in urban (Delhi, and Bengaluru district, Karnataka) and suburban (Alappuzha district, Kerala) settings of the country in three phases. METHODS: Across the randomly selected households in each study area, two to four containers treated with attracticide (experimental) and untreated (control) were placed and monitored by trained surveillance workers on weekly/ fortnightly basis for determining the presence of eggs, larvae and pupae. Container positivity, percent larvae, egg and pupae collected were determined during different phases and analyzed statistically using SPSS 18.0. RESULTS: Container positivity was found statistically significant at Bengaluru and Alappuzha, Kerala while in Delhi, it was found non-significant. Eggs collected from experimental containers were significantly higher in comparison to control at all the locations except Delhi. Also larvae collected from control containers were significantly higher at all the locations except Bengaluru. Pupae collected from control containers remained significantly higher at all the locations as no pupal formation was recorded from experimental containers. INTERPRETATION & CONCLUSION: The use of C21 attracticide hampered pupal formation, thus inhibiting adult population in the study areas. The study established that C21 attracticide was efficacious in the field conditions and has potential for use in surveillance and management of dengue and chikungunya mosquitoes.

Interaction of choline salts with artificial biological membranes: DSC studies elucidating cellular interactions.

To better understand the relationship between the relative cytotoxicity of diluted ionic liquids and their specific interaction with biological membranes, the thermotropic behavior of model lipid membrane systems formulated in a series of choline based organic salts was investigated. Unilamellar vesicles prepared from dipalmitoylphosphatidylcholine were exposed to a series of choline phosphate salts at a concentration of 10mM at pH7.40, and the gel to liquid-crystalline state transition was examined using differential scanning calorimetry. The choline salts that were observed to have a low relative toxicity in previous studies induced minimal changes in the lipid phase transition behavior of these model membranes. In contrast, the salts choline bis(2,4,4-trimethylpentyl)phosphinate and choline bis(2-ethylhexyl)phosphate, both of which were observed to have high relative toxicity, caused distinct disruptions in the lipid phase transition behavior, consistent with penetration of the salts into the acyl chains of the phospholipids. choline bis(2,4,4-trimethylpentyl)phosphinate reduced the Tm and enthalpy of the main transition of dipalmitoylphosphatidylcholine while choline bis(2-ethylhexyl)phosphate induced the equilibration of alternate phases.

Size-dependent effect of zinc oxide on toxicity and inflammatory potential of human monocytes.

With the rapid development of nanomedicines, it is important to understand their potential immunotoxicity. Zinc oxide (ZnO) nanoparticles have several applications in the pharmaceutical and biomedicine industries. This study investigates the effect of particles size (nano and micro) of ZnO on viability, phagocytosis, and cytokine induction in human monocytes, THP-1 cells, a model of the innate immune system. Cells were incubated with nano (approximately 100 nm) and micro (approximately 5 µm) sized ZnO particles in a concentration range of 10-100 µg/ml. The parameters measured included the MTT assay, phagocytosis assay, enzyme-linked immunosorbent assay (ELISA), gene expression, and DNA analysis. ZnO particles significantly decreased cell viability in a size- and concentration-dependent manner associated with significant alterations in phagocytic capacity of monocytes. Exposure of THP-1 cells to both sizes of ZnO stimulated and increased release of proinflammatory cytokines interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and IL-6, as well as chemokine IL-8, and upregulated the expression of monocyte chemoattractant protein-1 and cyclooxygenase-2 genes. However, ZnO particles did not markedly affect monocytes DNA. Collectively, these results suggest higher propensity of nano ZnO particles in inducing cytotoxicity and inflammation in human monocytes regardless of micro size, and caution needs to be taken concerning their biological application.

Spatial Recognition: A Temporal Tale of Multiple Window Spatial Registration.

Purpose: The performance ability of position logic circuitry of gamma-camera to superimpose the X-Y gains obtained from different pulse height analyzers is multiple window spatial registration (MWSR). This study was conducted to evaluate the feasibility of dual-tracer method using 99mTc and 131I to assess MWSR. Materials and Methods: The procedure was carried out on a dual-head gamma-camera with rectangular NaI (Tl) crystal using a point source containing 99mTc pertechnetate and 131I-NaI. Pixel coordinates, full width at half-maximum of point spread function at 364 keV and 140 keV, and pixels with maximum count of images for dual detectors were analyzed and compared. Results: The experiment demonstrated an excellent correlation between the X and Y coordinates identified on 364 keV and 140 keV images (Spearman's coefficient of rank correlation: 0.9, P < 0.0001). Intraclass correlation of studies performed on two separate occasions showed a good correlation (k = 0.87) demonstrating the reproducibility of the procedure. Conclusion: Dual-tracer method for evaluation of MWSR is a reproducible, accurate, and logical alternative to the routine National Electrical Manufacturers Association procedure.

Probing the molecular interactions between cholinium-based ionic liquids and insulin aspart: A combined computational and experimental study.

Despite extensive studies revealing the potential of cholinium-based ionic liquids (ILs) in protein stabilization, the nature of interaction between ILs' constituents and protein residues is not well understood. In this work, we used a combined computational and experimental approach to investigate the structural stability of a peptide hormone, insulin aspart (IA), in ILs containing a choline cation [Ch]+ and either dihydrogen phosphate ([Dhp]-) or acetate ([Ace]-) as anions. Although IA remained stable in both 1 M [Ch][Dhp] and 1 M [Ch][Ace], [Dhp]- exhibited a much stronger stabilization effect than [Ace]-. Both the hydrophilic ILs intensely hydrated IA and increased the number of water molecules in IA's solvation shell. Undeterred by the increased number of water molecules, the native state of IA's hydrophobic core was maintained in the presence of ILs. Importantly, our results reveal the importance of IL concentration in the medium which was critical to maintain a steady population of ions in the microenvironment of IA and to counteract the denaturing effect of water molecules. Through molecular docking, we confirm that the anions exert the dominant effect on the structure of IA, while [Ch]+ have the secondary influence. The computational results were validated using spectroscopic analyses (ultra-violet, fluorescence, and circular dichroism) along with dynamic light scattering measurements. The extended stability of IA at 30 °C for 28 days in 1 M [Ch][Dhp] and [Ch][Ace] demonstrated in this study reveals the possibility of stabilizing IA using cholinium-based ILs.

Identification of a novel agarolytic γ -Proteobacterium Microbulbifer maritimus and characterization of its agarase.

The phenotypic and agar degrading features of an unidentified marine bacteria was investigated. The strain was Gram-negative, obligatory aerobic and non motile. On the basis of several morphological features and a phylogenetic analysis of the genes coding for the 16S rDNA, this strain was identified as Microbulbifer maritimus. On solid agar medium, this isolate produced extracellular agarase which causes agar liquefaction around the colonies. An extracellular agarase was purified by ammonium sulfate precipitation, gel filtration and ion-exchange chromatography on DEAE-cellulose. The purified protein migrated as a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and it had a molecular mass of 75.2 kDa. The enzyme exhibited maximal activity at pH 7.5. The kinetic parameters of the enzyme were K(m) = 3 ± 0.19 mM, K(cat) = 160 ± 10 S(-1) and K(cat) /K(m) = 53 ± 10 S(-1) · mM(-1) .

A convenient first aid kit for chemical and biological agents and for radiation exposure.

The chemical and biological warfare agents are extremely toxic in nature. They act rapidly even in very small quantities and death may occur in minutes. Hence, physical and medical protection must be provided immediately to save life or avoid serious injury. A first aid kit has thus been developed for providing immediate relief from chemical and biological warfare agents (FAKCBW) with the objective of easy detection, personal decontamination, antidote for chemical warfare agents (like nerve agents, sulphur mustard, phosgene, cyanide, radiation exposure and bacterial agents), along with basic medication aid for pain, fever and inflammation. The kit box also includes a user friendly handbook with a simple standard operating procedure. In addition, the kit is rugged to withstand normal jerks, vibration and is water-proof.

Effectiveness of evidence-based intervention on social skill and communication among autism spectrum disorder children.

AIM: Evidence-based intervention is an effective method for improving autism spectrum disorder (ASD) in children on socialization, behavior, and communication and may have an impact on brain activity. The aim of this study is to find the effectiveness of picture exchange communication system (PECS) and parent-implemented intervention (PII) among ASD children. MATERIALS AND METHODS: Sixty ASD children who fulfilled the inclusion criteria were selected and assigned into control (n=30) and experimental (n=30) groups. The experimental group received evidence-based intervention with PECS and PII for 6 months, whereas the control group received routine care. The children were assessed for social relationship and reciprocity (SRR) and speech language communication (SLC) before and after the intervention. For the experimental group, a 3-month post-intervention was also assessed. Parametric and nonparametric statistical methods were used. RESULTS: The data showed that male nuclear family and birth order above 1 was more among ASD. Two-way RM ANOVA showed a significant difference among the groups and tests (P < 0.001) and interaction of groups with tests (P < 0.001). Experimental post-test-2, that is, after 6 months, showed significant improvement in SRR and SLC compared with the control group. CONCLUSION: The present study shows that the PECS and PII as a nursing strategy can improve ASD children socialization and communication.

Design of double sampling inspection plans for life tests under time censoring based on Pareto type IV distribution.

Sampling inspection plans for life tests, called reliability sampling plans, are generally employed to determine the acceptance or non-acceptance of the lot(s) of finished products by performing tests on the sampled items, measuring the lifetime of the items and observing the number of failures of items. Lifetime of individual items is a prime quality characteristic that can be treated as a continuous random variable and can be modeled by an appropriate probability distribution. In this article, double sampling plans for life tests under time censoring with a provision to draw two random samples and to admit a maximum of one failure in the combined samples are formulated assuming that the lifetime random variable follows a Pareto type IV distribution. A methodical procedure for the selection of the plan parameters using reliable life criterion with the desired discrimination protecting the interests of the producer and the consumer in terms of the acceptable reliable life and unacceptable reliable life is evolved. The operating ratio is used as a measure of discrimination in designing the proposed reliability sampling plans.

Imaging and Laboratory Workup for Melanoma.

Accurate diagnosis and staging of malignant melanoma remain crucial components in the overall treatment and prognosis of the patient. Advanced imaging modalities as well as laboratory testing continue to constitute an important part of the workup in melanoma and have seen several developments in recent years. The authors discuss imaging techniques and serum biomarkers used in the assessment of the melanoma patient.

Spectrophotometric Analysis of Fluoride Concentration in Dentifrices for Children in India.

Background: There is a need to monitor the fluoride content of dentifrices used for children in a country like India, where there is prevalence of endemic fluorosis. Aim: To evaluate the fluoride content of dentifrices for children available in India. Settings and Design: In vitro study in a laboratory setting. Methods: About 27 major supermarkets/departmental stores in Chennai city were approached by the investigator. All dentifrices indicated for children, available in these stores were included in the present study. A total of four different dentifrice brands were procured from these outlets. For each brand of dentifrice, three samples were randomly chosen and used for fluoride analysis. The fluoride content was assessed in triplet by using spectrophotometric analysis, by a single blinded examiner. The test sample was compared to a standard solution, in a calibration curve to determine the fluoride concentration. Results: The mean fluoride content of dentifrices, indicated for children was 449.5 ± 26.1 ppm. Conclusions: All brands of commercially available dentifrices indicated for children had optimum amount of fluoride.

Enhanced structural stability of insulin aspart in cholinium aminoate ionic liquids.

Cholinium aminoates [Ch][AA] have gained tremendous interest as a promising ionic liquid medium for the synthesis and storage of proteins. However, high alkalinity of [Ch][AA] limits its usage with pH-sensitive proteins. Here, we probed the structure, stability, and interactions of a highly unstable therapeutic protein, insulin aspart (IA), in a range of buffered [Ch][AA] (b-[Ch][AA]) using a combination of biophysical tools and in silico pipeline including ultraviolet-visible, fluorescence, and circular dichroism spectroscopies, dynamic light scattering measurements and molecular docking. b-[Ch][AA] used in the study differed in concentrations and their anionic counterparts. We reveal information on ion and residue specific solvent-protein interactions, demonstrating that the structural stability of IA was enhanced by a buffered cholinium prolinate. In comparison to the glycinate and alaninate anions, the hydrophilic prolinate anions established more hydrogen bonds with the residues of IA and provided a less polar environment that favours the preservation of IA in its active monomeric form, opening new opportunities for utilizing [Ch][AA] as storage medium.