Liver transplantation for hepatocellular carcinoma]

Hepatocellular carcinoma (HCC) is the most frequent primitive cancer of the liver. It mostly develops on cirrhotic livers. Orthotopic liver transplantation is the only treatment that definitively addresses both the metachronous occurrence risk of HCC and the underlying disease. Under Milan criteria, i.e. less than 3 nodules of 3 cm max in diameter, or 1 nodule of 5 cm maximum, OLT has been shown effective and provides with survival rates almost equal to those obtained with HCC free cirrhotic patients. In Rennes, 195 patients with early HCC on cirrhotic livers have been transplanted from January 1995 to June 2005. Global and disease free 8 years patient survival rates were 73 and 70%, respectively. These results were significantly altered when the recipient was female, the cirrhosis due to C virus and the patient of B blood group. Despite these excellent results, the principal limit to the application of transplantation for HCC remains the long period of time patients have to wait for a graft. During this period of time, growth of the tumour may drop the patient out of Milan criteria and subsequently from the waiting list. The role of chemoembolisation, liver resection and thermal ablation while the patient is waiting for a graft remains debatable.     

Are Essential Medicines in Malaysia Accessible, Affordable and Available?

Objective: To assess the pharmaceutical sector to know whether people have access to essential medicines. Setting: The study was conducted in 20 public health clinics, five public district drug stores and 20 private retail pharmacies selected randomly in five different areas randomly selected (four states and a federal territory). Method: The methodology used was adopted from the World Health Organization study protocol. The degree of attainment of the strategic pharmaceutical objectives of improved access is measured by a list of tested indicators. Access is measured in terms of the availability and affordability of essential medicines, especially to the poor and in the public sector. The first survey in the public health clinics and public district drug stores gathered information about current availability of essential medicines, prevalence of stock-outs and affordability of treatment (except drug stores). The second survey assessed affordability of treatment in public health clinics and private retail pharmacies. Main Outcome Measure Availability, stock-out duration, percent of medicines dispensed, accessibility and affordability of key medicines. Results The average availability of key medicines in the public health clinics for the country was 95.4%. The average stock-out duration of key medicines was 6.5 days. However, average availability of key medicines in the public district drug stores was 89.2%; with an average stock-out duration of 32.4 days. Medicines prescribed were 100% dispensed to the patients. Average affordability for public health clinics was 1.5 weeks salary and for the private pharmacies, 3.7 weeks salary. Conclusions: The present pharmaceutical situation in the context of essential medicines list implementation reflected that the majority of the population in Malaysia had access to affordable essential medicines. If medicines need to be obtained from the private sector, they are hardly affordable. Although the average availability of essential medicines in Malaysia was high being more than 95.0%, in certain areas in Sabah availability was less than 80.0% and still a problem.     

Quantitative variability in the biodistribution and in toxinokinetic studies of the three main alpha toxins from the Androctonus australis hector scorpion venom.

Scorpion stings represent a medical problem in numerous countries. The scorpion Androctonus australis hector produces three alpha toxins (Aah I to III), which are responsible for most of the lethality in mammals. These toxins act on sodium channel and do not cross-react immunologically. We used RIA and ELISA to measure the concentrations of these three toxins in plasma, urine and different organs after i.v. and s.c. injections of water extracts of venoms in rabbits or mice. In both animals, the toxins rapidly appeared in plasma after s.c. injection as it was previously described for the whole venom. However, the toxins disappeared from the blood more quickly than did other main components of the venom. Thus, serotherapy must be initiated immediately to prevent the toxin from reaching its target. We also detected the toxins in urine, kidneys, heart and lungs, but not in the brain. However, the concentration of Aah II was always lower than that of Aah I. Analysis of five samples of venom collected in different areas of southern Tunisia showed that a large polymorphism exists for the three toxins. This is yet another difficulty for serotherapy as there is no cross-antigenicity between them.     

Predictors of all‐cause mortality among patients hospitalized with influenza,respiratory syncytial virus,or SARS‐CoV‐2

BackgroundShared and divergent predictors of clinical severity across respiratory viruses may support clinical and community responses in the context of a novel respiratory pathogen.MethodsWe conducted a retrospective cohort study to identify predictors of 30‐day all‐cause mortality following hospitalization with influenza (N = 45,749; 2010‐09 to 2019‐05), respiratory syncytial virus (RSV; N = 24 345; 2010‐09 to 2019‐04), or severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2; N = 8988; 2020‐03 to 2020‐12; pre‐vaccine) using population‐based health administrative data from Ontario, Canada. Multivariable modified Poisson regression was used to assess associations between potential predictors and mortality. We compared the direction, magnitude, and confidence intervals of risk ratios to identify shared and divergent predictors of mortality.ResultsA total of 3186 (7.0%), 697 (2.9%), and 1880 (20.9%) patients died within 30 days of hospital admission with influenza, RSV, and SARS‐CoV‐2, respectively. Shared predictors of increased mortality included older age, male sex, residence in a long‐term care home, and chronic kidney disease. Positive associations between age and mortality were largest for patients with SARS‐CoV‐2. Few comorbidities were associated with mortality among patients with SARS‐CoV‐2 as compared with those with influenza or RSV.ConclusionsOur findings may help identify patients at greatest risk of illness secondary to a respiratory virus, anticipate hospital resource needs, and prioritize local prevention and therapeutic strategies to communities with higher prevalence of risk factors.     

Resistance of Xanthomonas oryzae pv. oryzae to Lytic Phage X2 by Spontaneous Mutation of Lipopolysaccharide Synthesis-Related Glycosyltransferase

Phage therapy is a promising biocontrol management on plant diseases caused by bacterial pathogens due to its specificity, efficiency and environmental friendliness. The emergence of natural phage-resistant bacteria hinders the application of phage therapy. Xanthomonas oryzae pv. oryzae (Xoo) is the causal agent of the devastating bacterial leaf blight disease of rice. Here, we obtained a spontaneous mutant C2R of an Xoo strain C2 showing strong resistance to the lytic phage X2. Analysis of the C2R genome found that the CDS2289 gene encoding glycosyltransferase acquired a frameshift mutation at the 180th nucleotide site, which also leads to a premature stop mutation at the 142nd amino acid. This mutation confers the inhibition of phage adsorption through the changes in lipopolysaccharide production and structure and bacterial surface morphology. Interestingly, glycosyltransferase-deficient C2R and an insertional mutant k2289 also showed reduced virulence, suggesting the trade-off costs of phage resistance. In summary, this study highlights the role of glycosyltransferase in interactions among pathogenic bacteria, phages and plant hosts, which provide insights into balanced coevolution from environmental perspectives.     

Fractal Analysis of a Non-Newtonian Fluid Flow in a Rough-Walled Pipe

The fully developed laminar flow of a viscous non-Newtonian fluid in a rough-walled pipe is considered. The fluid rheology is described by the power–law model (covering shear thinning, Newtonian, and shear thickening fluids). The rough surface of the pipe is considered to be fractal, and the surface roughness is measured using surface fractal dimensions. The main focus of this study lies in the theoretical investigation of the influence of the pipe surface roughness on the velocity profile and the Darcy friction factor of an incompressible non-Newtonian fluid. The plotted results demonstrate that shear thinning fluids are the most sensitive to the surface roughness compared with Newtonian and shear thickening fluids. For a particular value of the surface fractal dimension, there exists an intersection point where shear thinning, Newtonian, and shear thickening fluids behave the same way regarding the amplitude of the velocity profile and the friction factor. This approach has a variety of potential applications, for instance fluid dynamics in hydrology, blood flow in the cardiovascular system, and many industrial applications.     

Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells

Certain anticancer agents selectively target the nucleus of cancer cells. One such drug is 2-methoxyestradiol (2ME), which is used for treating lung cancer. To improve the therapeutic effectiveness of these agents, many new methods have been devised. 2ME was entrapped into the core of hydrophobic invasomes (INVA) covered with Phospholipon 90G and apamin (APA). The Box–Behnken statistical design was implemented to enhance the composition. Using Design-Expert software (Stat-Ease Inc., Minneapolis, MN), the INVA component quantities were optimized to obtain spherical particles with the smallest size, that is, a diameter of 167.8 nm. 2ME-INVA-APA significantly inhibited A549 cells and exhibited IC₅₀ of 1.15 ± 0.04 µg/mL, which is lower than raw 2ME (IC₅₀ 5.6 ± 0.2 µg/mL). Post 2ME-INVA-APA administration, a significant rise in cell death and necrosis was seen among the A549 cells compared to those treated with plain formula or 2ME alone. This effect was indicated by increased Bax expression and reduced Bcl-2 expression, as well as mitochondrial membrane potential loss. Moreover, the cell cycle analysis showed that 2ME-INVA-APA arrests the G2-M phase of the A549 cells. Additionally, it was observed that the micellar formulation of the drug increased the cell count in pre-G1, thereby exhibiting phenomenal apoptotic potential. Furthermore, it up-regulates caspase-9 and p53 and downregulates TNF-α and NF-κβ. Collectively, these findings showed that our optimized 2ME-INVA-APA could easily seep through the cell membrane and induce apoptosis in relatively low doses.