H5N1 Clade 2.2 Polymorphism Tracing Identifies Influenza Recombination and Potential Vaccine Targets

Highly pathogenic Influenza A H5N1 was first identified in Guangdong Province in 1996, followed by human cases in Hong Kong in 1997 1. The number of confirmed human cases now exceeds 300 and the associated Case Fatality Rate exceeds 60% 2. The genetic diversity of the serotype continues to increase. Four distinct clades or sub-clades have been linked to human cases 3.4. The gradual genetic changes identified in the sub-clades have been attributed to copy errors by viral encoded polymerases that lack an editing function, thereby resulting in antigenic drift 5. We traced polymorphism acquisition in Clade 2.2 sequences. We report here the concurrent acquisition of the same polymorphism by multiple, genetically distinct, Clade 2.2 sub-clades in Egypt, Russia and Ghana. These changes are not easily explained by the current theory of “random mutation” through copy error, and are more easily explained by recombination with a common source. This conclusion is supported by additional polymorphisms shared by Clade 2.2 isolates in Egypt, Nigeria and Germany including aggregation of regional polymorphisms from each of these areas into a single Nigerian human hemagglutinin gene

Development and validation of a rapid method for the detection of latrunculol A in plasma

Latrunculol A is a recently discovered 6,7-dihydroxy analog of the potent actin inhibitor latrunculin A. Latrunculol A has exhibited greater cytotoxicity than latrunculin A against both murine and human colon tumor cell lines in vitro. Currently, there are no reports regarding the bioavailability of latrunculol A in vivo. This study was undertaken as a prelude to pharmacokinetic assessments and it is the first work where bioavailability of latrunculol A was studied. In the present work, a simple plasma preparation and a rapid HPLC method have been developed. Mouse plasma containing latrunculol A was first treated by acetonitrile and then centrifuged at 14,000 rpm at 4 °C for 25 min. The supernatant was injected in an HPLC system comprising a Waters Symmetry NH2 column, a mobile phase of acetonitrile/water (95/5, v/v), a flow rate of 1.0 mL/min, at 220 nm. The method was validated by parameters including a good linear correlation, a limit of quantification of 9 ng/mL, and a good precision with a coefficient variation of 1.65, 1.86, and 1.26% for 20, 400, and 800 ng/mL, respectively. With this simple method, excellent separation and sensitivity of latrunculol A are achieved, thus allowing a rapid analysis of the plasma samples for absorption, distribution, and metabolism studies

Prospects for terahertz imaging the human skin cancer with the help of gold-nanoparticles-based terahertz-to-infrared converter

The design is suggested, and possible operation parameters are discussed, of an instrument to inspect a skin cancer tumour in the terahertz (THz) range, transferring the image into the infrared (IR) and making it visible with the help of standard IR camera. The central element of the device is the THz-to-IR converter, a Teflon or silicon film matrix with embedded 8.5 nm diameter gold nanoparticles. The use of external THz source for irradiating the biological tissue sample is presumed. The converter's temporal characteristics enable its performance in a real-time scale. The details of design suited for the operation in transmission mode (in vitro) or on the human skin in reflection mode {in vivo) are specified.Comment: To be published in the proceedings of the FANEM2018 workshop - Minsk, 3-5 June 201

Blast Shock Wave Mitigation Using the Hydraulic Energy Redirection and Release Technology

A hydraulic energy redirection and release technology has been developed for mitigating the effects of blast shock waves on protected objects. The technology employs a liquid-filled plastic tubing as a blast overpressure transformer to transfer kinetic energy of blast shock waves into hydraulic energy in the plastic tubings. The hydraulic energy is redirected through the plastic tubings to the openings at the lower ends, and then is quickly released with the liquid flowing out through the openings. The samples of the specifically designed body armor in which the liquid-filled plastic tubings were installed vertically as the outer layer of the body armor were tested. The blast test results demonstrated that blast overpressure behind the body armor samples was remarkably reduced by 97% in 0.2 msec after the liquid flowed out of its appropriate volume through the openings. The results also suggested that a volumetric liquid surge might be created when kinetic energy of blast shock wave was transferred into hydraulic energy to cause a rapid physical movement or displacement of the liquid. The volumetric liquid surge has a strong destructive power, and can cause a noncontact, remote injury in humans (such as blast-induced traumatic brain injury and post-traumatic stress disorder) if it is created in cardiovascular system. The hydraulic energy redirection and release technology can successfully mitigate blast shock waves from the outer surface of the body armor. It should be further explored as an innovative approach to effectively protect against blast threats to civilian and military personnel

Computational Analysis of Pulsed Radiofrequency Ablation in Treating Chronic Pain

In this paper, a parametric study has been conducted to evaluate the effects of frequency and duration of the short burst pulses during pulsed radiofrequency ablation (RFA) in treating chronic pain. Affecting the brain and nervous system, this disease remains one of the major challenges in neuroscience and clinical practice. A two-dimensional axisymmetric RFA model has been developed in which a single needle radiofrequency electrode has been inserted. A finite-element-based coupled thermo-electric analysis has been carried out utilizing the simplified Maxwell’s equations and the Pennes bioheat transfer equation to compute the electric field and temperature distributions within the computational domain. Comparative studies have been carried out between the continuous and pulsed RFA to highlight the significance of pulsed RFA in chronic pain treatment. The frequencies and durations of short burst RF pulses have been varied from 1 Hz to 10 Hz and from 10 ms to 50 ms, respectively. Such values are most commonly applied in clinical practices for mitigation of chronic pain. By reporting such critical input characteristics as temperature distributions for different frequencies and durations of the RF pulses, this computational study aims at providing the first-hand accurate quantitative information to the clinicians on possible consequences in those cases where these characteristics are varied during the pulsed RFA procedure. The results demonstrate that the efficacy of pulsed RFA is significantly dependent on the duration and frequency of the RF pulses

Characteristics of mentally ill offenders from 100 psychiatric court reports

<p>Abstract</p> <p>Background</p> <p>There is an increasing probability that the psychiatrist will, willingly or not, come into contact with mentally ill offenders in the course of their practice. There are increasing rates of violence, substance abuse and other psychiatric disorders that are of legal importance. Therefore, the aim of this work was to investigate the rates of different mental disorders in 100 court reports and to investigate the characteristics of mentally ill offenders.</p> <p>Methods</p> <p>All cases referred from different departments of the legal system to the forensic committee for assessment of legal accountability over 13-months duration were included. A specially designed form was prepared for data collection. Cases were classified into five groups: murder, robbery, financial offences, violent and simple offences and a group for other offences. Data were subjected to statistical analysis and comparisons between different groups of subjects were performed by analysis of variance (ANOVA).</p> <p>Results</p> <p>Men constituted 93% of cases. In all, 73% of offenders were younger than 40 years old. Schizophrenia cases made up 13% of the total, substance related cases constituted 56% and amphetamine cases alone made up 21%; 10% of cases were antisocial personality disorders, and 51% of cases were classified as having a low education level. Unemployment was found in 34% of cases. The final decision of the forensic committee was full responsibility in 46% of cases and partial responsibility in 11% of cases, with 33% considered non-responsible. A total of 58% of cases had had contact with psychiatric healthcare prior to the offence and in 9% of cases contact had been in the previous 12 weeks. A history of similar offences was found in 32% of cases. In all, 14% of the offences were murders, 8% were sexual crimes, and 31% were violent/simple crimes.</p> <p>Conclusions</p> <p>The ability of the legal system to detect cases was good, while the ability of the healthcare system to predict crimes and offences was weak, as 58% of cases had had previous contact with the healthcare system previously. Substance abuse, especially amphetamine abuse, played an important role.</p

Genome-Wide Association Studies of the PR Interval in African Americans

The PR interval on the electrocardiogram reflects atrial and atrioventricular nodal conduction time. The PR interval is heritable, provides important information about arrhythmia risk, and has been suggested to differ among human races. Genome-wide association (GWA) studies have identified common genetic determinants of the PR interval in individuals of European and Asian ancestry, but there is a general paucity of GWA studies in individuals of African ancestry. We performed GWA studies in African American individuals from four cohorts (n = 6,247) to identify genetic variants associated with PR interval duration. Genotyping was performed using the Affymetrix 6.0 microarray. Imputation was performed for 2.8 million single nucleotide polymorphisms (SNPs) using combined YRI and CEU HapMap phase II panels. We observed a strong signal (rs3922844) within the gene encoding the cardiac sodium channel (SCN5A) with genome-wide significant association (p<2.5×10−8) in two of the four cohorts and in the meta-analysis. The signal explained 2% of PR interval variability in African Americans (beta  = 5.1 msec per minor allele, 95% CI  = 4.1–6.1, p = 3×10−23). This SNP was also associated with PR interval (beta = 2.4 msec per minor allele, 95% CI = 1.8–3.0, p = 3×10−16) in individuals of European ancestry (n = 14,042), but with a smaller effect size (p for heterogeneity <0.001) and variability explained (0.5%). Further meta-analysis of the four cohorts identified genome-wide significant associations with SNPs in SCN10A (rs6798015), MEIS1 (rs10865355), and TBX5 (rs7312625) that were highly correlated with SNPs identified in European and Asian GWA studies. African ancestry was associated with increased PR duration (13.3 msec, p = 0.009) in one but not the other three cohorts. Our findings demonstrate the relevance of common variants to African Americans at four loci previously associated with PR interval in European and Asian samples and identify an association signal at one of these loci that is more strongly associated with PR interval in African Americans than in Europeans

Presymptomatic breast cancer in Egypt: role of BRCA1 and BRCA2 tumor suppressor genes mutations detection

<p>Abstract</p> <p>Background</p> <p>Breast cancer is one of the most common diseases affecting women. Inherited susceptibility genes, <it>BRCA1 </it>and <it>BRCA2</it>, are considered in breast, ovarian and other common cancers etiology. <it>BRCA1 </it>and <it>BRCA2 </it>genes have been identified that confer a high degree of breast cancer risk.</p> <p>Objective</p> <p>Our study was performed to identify germline mutations in some exons of <it>BRCA1 </it>and <it>BRCA2 </it>genes for the early detection of presymptomatic breast cancer in females.</p> <p>Methods</p> <p>This study was applied on Egyptian healthy females who first degree relatives to those, with or without a family history, infected with breast cancer. Sixty breast cancer patients, derived from 60 families, were selected for molecular genetic testing of <it>BRCA1 </it>and <it>BRCA2 </it>genes. The study also included 120 healthy first degree female relatives of the patients, either sisters and/or daughters, for early detection of presymptomatic breast cancer mutation carriers. Genomic DNA was extracted from peripheral blood lymphocytes of all the studied subjects. Universal primers were used to amplify four regions of the <it>BRCA1 </it>gene (exons 2,8,13 and 22) and one region (exon 9) of <it>BRCA2 </it>gene using specific PCR. The polymerase chain reaction was carried out. Single strand conformation polymorphism assay and heteroduplex analysis were used to screen for mutations in the studied exons. In addition, DNA sequencing of the normal and mutated exons were performed.</p> <p>Results</p> <p>Mutations in both <it>BRCA1 </it>and <it>BRCA2 </it>genes were detected in 86.7% of the families. Current study indicates that 60% of these families were attributable to <it>BRCA1 </it>mutations, while 26.7% of them were attributable to <it>BRCA2 </it>mutations. Results showed that four mutations were detected in the <it>BRCA1 </it>gene, while one mutation was detected in the <it>BRCA2 </it>gene. Asymptomatic relatives, 80(67%) out of total 120, were mutation carriers.</p> <p>Conclusions</p> <p><it>BRCA1 </it>and <it>BRCA2 </it>genes mutations are responsible for a significant proportion of breast cancer. <it>BRCA </it>mutations were found in individuals with and without family history.</p

The Ionizing Radiation-Induced Bystander Effect: Evidence, Mechanism, and Significance

It has long been considered that the important biological effects of ionizing radiation are a direct consequence of unrepaired or misrepaired DNA damage occurring in the irradiated cells. It was presumed that no effect would occur in cells in the population that receive no direct radiation exposure. However, in vitro evidence generated over the past two decades has indicated that non-targeted cells in irradiated cell cultures also experience significant biochemical and phenotypic changes that are often similar to those observed in the targeted cells. Further, nontargeted tissues in partial body-irradiated rodents also experienced stressful effects, including oxidative and oncogenic effects. This phenomenon, termed the “bystander response,” has been postulated to impact both the estimation of health risks of exposure to low doses/low fluences of ionizing radiation and the induction of second primary cancers following radiotherapy. Several mechanisms involving secreted soluble factors, oxidative metabolism, gap-junction intercellular communication, and DNA repair, have been proposed to regulate radiation-induced bystander effects. The latter mechanisms are major mediators of the system responses to ionizing radiation exposure, and our knowledge of the biochemical and molecular events involved in these processes is reviewed in this chapter