Hepatocellular carcinoma in Pakistan: where do we stand?

Context: From the 1970s till the mid 1990s, hepatitis B was the most common etiological factor for hepatocellular carcinoma (HCC) in Pakistan. Afterwards, a shift in HCC etiology was observed with a steady rise in hepatitis C virus (HCV) related HCC cases. HCV-3a, which is the most prevalent genotype, is also most frequent in HCV related HCC. There was an increase in the proportion of non-B non-C (NBNC) HCC cases as well, which might be attributed to an increase in non-alcoholic fatty liver disease. Evidence Acquisition: The age-standardized rate for HCC is 7.64/100 000 in males and 2.8/100 000 in females. Male to female ratio is 3.6:1. Usual age of presentation is in the fifth and sixth decade. Most patients present with advanced disease, as they are not in a regular surveillance program. This is more so for patients with NBNC chronic liver disease. As many sonologists in Pakistan are practicing without sufficient training to pick up early lesions, alpha-fetoprotein is still recommended to compliment ultrasound in the surveillance of HCC. Results: Majority of HCC patients present with nonresectable disease. Interventions such as transarterial chemoembolization, radiofrequency ablation, resection and chemotherapy including sorafenib are available in selected centers. Pakistan appears to be in an area of intermediate endemicity for HCC. There is a need for population based epidemiological studies to estimate the exact disease burden. Conclusions: Measures to prevent the spread of hepatitis C and B can slow down the epidemic rise in the incidence of HCC in the coming decades. There is a need to implement a proper surveillance program to identify HCC cases at an early stage

MGP Panel is a comprehensive targeted genomics panel for molecular profiling of multiple myeloma patients

PURPOSE: We designed a comprehensive multiple myeloma (MM) targeted sequencing panel to identify common genomic abnormalities in a single assay and validated it against known standards. EXPERIMENTAL DESIGN: The panel comprised 228 genes/exons for mutations, 6 regions for translocations, and 56 regions for copy number abnormalities (CNAs). Toward panel validation, targeted sequencing was conducted on 233 patient samples and further validated using clinical fluorescence in situ hybridization (FISH) (translocations), multiplex ligation probe analysis (MLPA) (CNAs), whole genome sequencing (WGS) (CNAs, mutations, translocations) or droplet digital PCR (ddPCR) of known standards (mutations). RESULTS: Canonical IgH translocations were detected in 43.2% of patients by sequencing, and aligned with FISH except for one patient. CNAs determined by sequencing and MLPA for 22 regions were comparable in 103 samples and concordance between platforms was R2=0.969. VAFs for 74 mutations were compared between sequencing and ddPCR with concordance of R2=0.9849. CONCLUSIONS: In summary, we have developed a targeted sequencing panel that is as robust or superior to FISH and WGS. This molecular panel is cost effective, comprehensive, clinically actionable and can be routinely deployed to assist risk stratification at diagnosis or post-treatment to guide sequencing of therapies

Experimental and theoretical studies of Rhodamine B direct dye sorption onto clay-cellulose composite

Dyes are one of the main water pollutants and many biological and environmental problems are associated with them. Rhodamine B (RhB) is one of the most commonly used dye in the textile, printing, paints, and paper industry. The present work reports the sorptive removal of Rhodamine B direct dye from wastewater onto developed cellulose and clay composites. Sorbent material cellulose (48 g) was extracted from 80 g of bagasse. Then cellulose and two types of acid-activated clays were used to make efficient sorbent namely, composite I and II. Various characterization techniques were used to study the physiochemical properties of the synthesized composites. Different sorption affecting parameters were optimized such as initial dye concentration, time, temperature, pH, and composite dose for the efficient sorption of RhB onto composites. Equilibrium time was 60 min for composite-I and 80 min for composite-II Non-linear equilibrium isotherm and kinetic models demonstrated the fitness of Pseudo-second order and Redlich-Peterson isotherm. Composite-I and II removed 85.9% and 95.6% of RhB at pH 2 in 120 min, respectively. The sorption efficiency was checked, and sorbents were applied to real textile effluent which showed promising removal efficiency of over 90%. To confirm the experimental results, computational optimization and vibrational calculations were carried out using the Gaussian 09 program package with 3–21 G, 6–311 G, and 6–311+G basic sets. Geometric parameters showed the planar geometry. In the case of FTIR spectra, fundamental ring vibrations were observed with C-H and C-C. This study suggests that the developed composites have exceptional sorption ability to remove the dye contents from aqueous media

Starch and polyvinyl alcohol encapsulated biodegradable nanocomposites for environment friendly slow release of urea fertilizer

Low nitrogen (N) use efficiency from urea fertilizers due to environmental losses results in high cost of fertilizers for agricultural productions. Coating of urea with biodegradable polymers makes them effective for control and efficient N release. In this study, starch and polyvinyl alcohol (PVA) were used in combination with acrylic acid (AA), citric acid (CA) and maleic acid (MA) for the coating of urea prills. Different formulations of the coating were prepared and applied on urea prills such as urea coated with starch (10%) and PVA (5%) with acrylic acid: 2, 4 and 6% (USP-A2, USP-A4, USP-A6), with citric acid: 2, 4 and 6% (USP-C2, USP-C4, USP-C6), and with maleic acid: 2, 4 and 6% (USP-M2, USP-M4, USP-M6). After urea coating in fluidized bed coater, all uncoated and coated urea samples were characterized by scanning electron spectroscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), crushing strength and UV-Vis spectroscopy. The morphological and XRD analysis indicated that a new uniform coating with no new phase transformation occurred. Among all urea coated samples, USP-A2 and USP-C2 showed the highest crushing strengths: 12.08 and 13.67 N with nitrogen release efficiency of 70.10 and 50.74% respectively. All coated urea samples improved the spinach plants’ foliage yield, chlorophyll content, N-uptake and apparent nitrogen recovery (ANR) than uncoated urea and control plants. However, USP-A2 and USP-C2 provided promising results among all coated samples with dry foliage yield (2208 ± 92 and 2428 ± 83 kg/ha), chlorophyll (34 ± 0.6 and 34 ± 0.4 mg/g), N-uptake (88 ± 4 and 95 ± 6 kg/ha) and ANR (59 ± 4 and 67 ± 6%). Therefore, urea prills coated with a combination of biodegradable polymers can be a better choice for the farmers to enhance agronomical productions by controlling the fertilizer nutrient release rate

Toxicological effects of patulin mycotoxin on the mammalian system: an overview

Abstract The mycotoxin PAT (4-hydroxy-4H-furo[3,2c]pyran-2[6H]-one) is a secondary metabolic product of molds such as Penicillium, Aspergillus, and Byssochlamys species. PAT is a common contaminant of fruit and vegetable based products, most notably apples. Despite PAT's original discovery as an antibiotic, it has come under heavy scrutiny for its potential to impart negative health effects. Studies investigating these health effects have proved its toxic potential. PAT occurrence in the food commodities poses a serious threat and necessitates novel and cost-effective mitigation methods to remove it from food products. It also creates a demand to improve handling and food processing techniques. With this being the case, several studies have been devoted to understanding the key biological and chemical attributes of PAT. While past research has elucidated a great deal, PAT contamination continues to be a challenge for the food industry. Here, we review its influence within the mammalian system, including its regulation, incidences of experimental evidence of PAT toxicity, its interaction with intracellular components, and the effects of PAT induced systemic toxicity on vital organs. Finally, key areas where future PAT research should focus to best control the PAT contamination problem within the food industry have been addressed.</jats:p

Macromolecular crowder polyethylene glycol delayed the aggregation of chromium-treated bovine serum albumin

The structure of proteins is greatly affected by various interacting xenobiotic and lead to the formation of aggregates. Chromium metal, which was initially considered innocent as a nutrient, has been found to induce some abnormalities in the human body recently. Aggregate formation is associated with the occurrence of pathological conditions such as systemic amyloidosis, cystic fibrosis, etc. To have a deeper insight into aggregation susceptibility and structural stability of bovine serum albumin on treating with hexavalent chromium Cr(VI) and the consequences of macromolecular crowding on the native conformation of the protein, the chromium concentration ranged from 0-100 µM where K2Cr2O7 was used as the Cr (VI) source. Disruption of native bovine serum albumin (BSA) assembly and formation of aggregates at 50 µM Cr(VI) was unveiled by increased turbidity and fluorescence at 350 nm, reduced intrinsic fluorescence with 10 nm and 20 nm blue shifted enhanced ANS spectra respectively. Significantly enhanced, the ThT fluorescence alone side sigmoidal curve with no lag phase and a 10 nm red shift in congo red spectra sustained conformational changes and indicated aggregation of BSA upon incubation with Cr(VI). Circular dichroism (CD) results showed the disappearance of negative minima at 208 and 222 nm, which confirms the transition of native helical structure to non-native beta sheets. Furthermore, the comet assay showed that Cr-treated BSA aggregates were found to be genotoxic, as an increase in tail length of 11.3 μm had been observed. Crowded microenvironment was mimicked by PEG-4000; a polyethylene glycol, was witnessed to prominently preserve conformational stability of BSA upon treatment with Cr(VI) as all results observed were close to that of native. The decrease in turbidity, fluorescence at 350 nm accompanied by a reduction in 8-anilinonaphthalene-1-sulfonic acid (ANS) and thioflavin T (ThT) fluorescence further verified the inhibition of aggregate formation in the presence of PEG-4000. Furthermore, the increased intrinsic fluorescence, decreased congo red absorption and reduced tail length of 3.4 μm in the comet assay were in co-relation with the above data. The macromolecular crowder PEG-4000 was efficient in delaying the aggregation of Cr-treated BSA, as the kinetics showed a sigmoidal curve with the lag phase. Based on these findings, it could be hypothesized that the native structure was maximally retained in the presence of 100 mg/mL of PEG-4000, demonstrating braking of aggregate formation. It can be established that explicit consideration of macromolecular crowding using a relevant range of inert crowding agents must be a prerequisite for studies concerning intracellular conformational behavior of proteins and enhanced their stability under stress conditions and devising protein formulations with enhanced conformational stability