Subtype 1b Research Articles

A Geophysical Review of the Seabed Methane Seepage Features and Their Relationship with Gas Hydrate Systems

Seabed methane seepage has gained attention from all over the world in recent years as an important source of greenhouse gas emission, and gas hydrates are also regarded as a key factor affecting climate change or even global warming due to their shallow burial and poor stability. However, the relationship between seabed methane seepage and gas hydrate systems is not clear although they often coexist in continental margins. It is of significance to clarify their relationship and better understand the contribution of gas hydrate systems or the deeper hydrocarbon reservoirs for methane flux leaking to the seawater or even the atmosphere by natural seepages at the seabed. In this paper, a geophysical examination of the global seabed methane seepage events has been conducted, and nearby gas hydrate stability zone and relevant fluid migration pathways have been interpreted or modelled using seismic data, multibeam data, or underwater photos. Results show that seabed methane seepage sites are often manifested as methane flares, pockmarks, deep-water corals, authigenic carbonates, and gas hydrate pingoes at the seabed, most of which are closely related to vertical fluid migration structures like faults, gas chimneys, mud volcanoes, and unconformity surfaces or are located in the landward limit of gas hydrate stability zone (LLGHSZ) where hydrate dissociation may have released a great volume of methane. Based on a comprehensive analysis of these features, three major types of seabed methane seepage are classified according to their spatial relationship with the location of LLGHSZ, deeper than the LLGHSZ (A), around the LLGHSZ (B), and shallower than LLGHSZ (C). These three seabed methane seepage types can be further divided into five subtypes considering whether the gas source of seabed methane seepage is from the gas hydrate systems or not. We propose subtype B2 represents the most important seabed methane seepage type due to the high density of seepage sites and large volume of released methane from massive focused vigorous methane seepage sites around the LLGHSZ. Based on the classification result of this research, more measures should be taken for subtype B2 seabed methane seepage to predict or even prevent ocean warming or climate change.

Consistency of spatial dynamics of HIV-1 and HCV among HIV-1/HCV coinfected drug users in China

BackgroundAs the transmission routes of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) are similar, previous studies based on separate research on HIV-1 and HCV assumed a similar transmission pattern. However, few studies have focused on the possible correlation of the spatial dynamics of HIV-1 and HCV among HIV-1/HCV coinfected patients.MethodsA total of 310 HIV-1/HCV coinfected drug users were recruited in Yingjiang and Kaiyuan prefectures, Yunnan Province, China. HIV-1 env, p17, pol and HCV C/E2, NS5B fragments were amplified and sequenced from serum samples. The genetic characteristics and spatial dynamics of HIV-1 and HCV were explored by phylogenetic, bootscanning, and phylogeographic analyses.ResultsAmong HIV-1/HCV coinfected drug users, eight HCV subtypes (1a, 1b, 3a, 3b, 6a, 6n, 6v, and 6u) and two HIV-1 subtypes (subtype B and subtype C), three HIV-1 circulating recombinant forms (CRF01_AE, CRF07_BC and CRF08_BC), and four unique recombinant forms (URF_BC, URF_01B, URF_01C and URF_01BC) were identified. HCV subtype 3b was the most predominant subtype in both Yingjiang and Kaiyuan prefectures. The dominant circulating HIV-1 subtypes for drug users among the two areas were CRF08_BC and URF_BC. Maximum clade credibility trees revealed that both HIV-1 and HCV were transmitted from Yingjiang to Kaiyuan.ConclusionsThe spatial dynamics of HIV-1 and HCV among HIV-1/HCV coinfected drug users seem to have high consistency, providing theoretical evidence for the prevention of HIV-1 and HCV simultaneously.

Epidemiology of hepatitis C virus infection in ColombiaEpidemiologia da infecção pelo vírus da hepatite C na Colômbia

RESUMENObjetivo.Describir la epidemiología de la infección por el virus de la hepatitis C (VHC) en Colombia.Métodos.Revisión crítica de los estudios de epidemiología de la infección por VHC en Colombia mediante búsqueda de artículos originales y revisiones de tema publicados en el período 1989 a 2020 en las bases de datos PubMed, SciELO y ScienceDirect. Además, se revisaron los informes del Instituto Nacional de Salud y de la Cuenta de Alto Costo del Ministerio de Salud y Protección Social.Resultados.Los datos de seroprevalencia de anticuerpos anti-VHC en donantes de sangre están en un rango de 1,5% a 0,32%, que corresponden a los informes del inicio y el final del período de estudio, respectivamente. En la población con factores de riesgo se observa una alta prevalencia de infección por VHC, aunque con variaciones a lo largo del tiempo. Con respecto a los genotipos de VHC en Colombia, se han identificado los genotipos 1, 2, 3 y 4 (subgenotipos 1a, 1b, 2a y 3a).Conclusiones.En el período de observación, se describe una disminución en la seroprevalencia de la infección por VHC en donantes de sangre y en pacientes en tratamiento con hemodiálisis en Colombia, lo que demuestra el impacto de las políticas de sangre segura y las medidas de bioseguridad. Los estudios en personas que usan drogas ilícitas por vía inyectable indican una alta prevalencia de infección, con diferencias según la región del país. El genotipo 1, subgenotipo 1b, del VHC es el más frecuente en los distintos estudios realizados en Colombia, y el informe más reciente de la Cuenta de Alto Costo del Ministerio de Salud y Protección Social señala que el genotipo 4 es el segundo genotipo más frecuente en el país.

Assessing hepatitis C virus distribution among vulnerable populations in London using whole genome sequencing: results from the TB-REACH study

Background: Injecting drugs substantially increases the risk of hepatitis C virus (HCV) infection and is common in vulnerable population groups, such as the homeless and prisoners. Capturing accurate data on relative genotype distribution within these groups is essential to inform strategies to reduce HCV transmission. The aim of this study was to utilise a next-generation whole-genome sequencing method recently validated by Public Health England, in order to produce near complete HCV genomes. Methods: In total, 98 HCV positive patients were recruited from homeless hostels and drug treatment services through the National Health Services (NHS) Find and Treat (F&T) Service between May 2011 and June 2013 in London, UK. Samples were sequenced by Next-generation sequencing, with 88 complete HCV genomes constructed by a de novo assembly pipeline. They were analysed phylogenetically for an estimate of their genetic distance. Results: Of the 88 complete HCV genomes, 50/88 (56.8%) were genotype 1; 32/88 (36.4%) genotype 3; 4/88 (4.5%) genotype 2; and 1/88 (1.1%) for genotypes 4 and 6 each. Subtype 1a had the highest number of samples (51.1%), followed by subtype 3a (35.2%), 1b (5.7%), and 2b (3.4%). Samples collected from drug treatment services had the highest number of genotype 1 (69%); genotypes 4 and 6 were only found from samples collected in homeless shelters. Small clusters of highly related genomic sequences were observed both across and within the vulnerable groups sampled. Conclusions: Subsequent phylogenetic analysis provides a first indication that there are related HCV sequences amongst the three vulnerable population groups, reflecting their overlapping social behaviours. This study is the first presentation of whole genome HCV sequences from such vulnerable groups in London and paves the way for similar research in the future.

Genetic Diversity of Porcine Circovirus Subtypes from Aborted Sow Fetuses in Vietnam.

Porcine circovirus type 3 (PCV3) is an emerging circovirus that is highly distributed among swine worldwide and associated with porcine dermatitis and nephropathy syndrome, reproductive failure, and multisystemic inflammation. Here, we investigated and characterized PCV3 from aborted fetuses in Vietnam. We found that the whole genomes of PCV3 collected in these Vietnamese pig farms share 98.4-99.45% sequence identity with reference PCV3 sequences. Several distinct mutation were identified in both the Rep protein and Cap protein of these strains. These strains were clustered into two distinct subtypes (3a1 and 3b). This study contributes to a better understanding of the molecular characteristics and genetic diversity of PCV3 in Vietnam.

Seroprevalence and molecular diversity of Human Herpesvirus 8 among people living with HIV in Brazzaville, Congo

Human herpesvirus 8 (HHV8) is endemic in Africa, although studies of this infection are rare in Congo. We evaluated seroprevalence and HHV-8 diversity among people living with HIV. We included 353 patients receiving highly active antiretroviral therapy. Antibodies against HHV-8 latency-associated nuclear antigen were detected by indirect immunofluorescence. In HHV-8 positive patients, we performed HHV-8 quantification in blood and saliva by real-time PCR and typing by Sanger sequencing of K1 open reading frame. HHV-8 seroprevalence was 19%, being male (odd ratio [OR] = 1.741, [95% Confidence interval {CI}, 0.97–3.07]; p = 0.0581) and having multiple sex partners before HIV diagnosis (OR = 1.682, [CI 95%, 0.97–2.92]; p = 0.0629) tended to be associated with HHV-8 seropositivity. Of the 64 HHV-8 seropositive patients, HHV-8 DNA was detected in 10 (16%) in saliva, 6 (9%) in whole-blood and in 2 (3%) in both whole-blood and saliva. Three out of 6 HHV-8 strains were subtypes A5, 2 subtype B1 and 1 subtype C. HHV-8 seroprevalence was relatively low with more frequent carriage in men, associated with asymptomatic oral excretion and a predominance of subtype A5. These data tend to support the hypothesis of horizontal transmission in people living with HIV in Brazzaville.

Spatiotemporal Phylodynamics of Hepatitis C Among People Who Inject Drugs in India.

Implementing effective interventions for HCV requires a detailed understanding of local transmission dynamics and geospatial spread. Little is known about HCV phylodynamics, particularly among high-burden populations, such as people who inject drugs (PWID). We used 483 HCV sequences and detailed individual-level data from PWID across four Indian cities. Bayesian phylogeographic analyses were used to evaluate transmission hotspots and geospatial diffusion of the virus. Phylogenetic cluster analysis was performed to infer epidemiologic links and factors associated with clustering. A total of 492 HIV sequences were used to draw comparisons within the same population and, in the case of coinfections, evaluate molecular evidence for shared transmission pathways. Overall, 139/483 (28.8%) of HCV sequences clustered with a median cluster size of 3 individuals. Genetically linked participants with HCV were significantly younger and more likely to be infected with HCV subtype 3b as well as to live and inject close to one another. Phylogenetic evidence suggests likely ongoing HCV infection/reinfection with limited support for shared HIV/HCV transmission pathways. Phylogeographic analyses trace historic HCV spread back to Northeastern India and show diffusion patterns consistent with drug trafficking routes. This study characterizes HCV phylodynamics among PWID in a low and middle-income country setting. Heterogeneity and recent genetic linkage of HCV across geographically disparate Indian states suggest that targeted interventions could help prevent reimportation of virus through drug trafficking routes.

Phylogenetic tree of NS5A gene of hepatitis C virus from infected Iraqi patients

Hepatitis C is a liver illness caused by the hepatitis C virus (HCV). Acute and chronic hepatitis can be caused by the virus. Hepatitis C infection affects an estimated 71 million people worldwide. Two hundred blood samples were collected (128 males and 72 females), ranged in age from 4 to 80 years and diagnosed through a rapid test and the real time-PCR from the teaching medical city hospital in Baghdad from October 2018 until April 2019. The results showed that 89 samples were positive for HCV by serological tests, and other samples are not. Also, the most frequent age of infection of HCV was between 51 and 80 years. In all samples, the partial region of the NS5A gene was successfully amplified and sequenced. PCR-sequencing revealed three subtyping were; subtype 1a, 1b, and 4a. Phylogenetic analysis revealed subtype concordance of 99 % with a bootstrap hepatitis C virus subtype 1b isolate AASN1 Iraq (ID:MT554101.1). The clusters including HCV subtype 1a isolate AASN20 Iraq (ID:MT554100.1) the identical 96 %, and the clusters including HCV subtype 4a isolate AASN35 Iraq (ID:MT554099.1) the identical 99%.

Nerve growth factor and glutamate increase the density and expression of substance P-containing nerve fibers in healthy human masseter muscles

Nocifensive behavior induced by injection of glutamate or nerve growth factor (NGF) into rats masseter muscle is mediated, in part, through the activation of peripheral NMDA receptors. However, information is lacking about the mechanism that contributes to pain and sensitization induced by these substances in humans. Immunohistochemical analysis of microbiopsies obtained from human masseter muscle was used to investigate if injection of glutamate into the NGF-sensitized masseter muscle alters the density or expression of the NMDA receptor subtype 2B (NR2B) or NGF by putative sensory afferent (that express SP) fibers. The relationship between expression and pain characteristics was also examined. NGF and glutamate administration increased the density and expression of NR2B and NGF by muscle putative sensory afferent fibers (P < 0.050). This increase in expression was greater in women than in men (P < 0.050). Expression of NR2B receptors by putative sensory afferent fibers was positively correlated with pain characteristics. Results suggest that increased expression of peripheral NMDA receptors partly contributes to the increased pain and sensitivity induced by intramuscular injection of NGF and glutamate in healthy humans; a model of myofascial temporomandibular disorder (TMD) pain. Whether a similar increase in peripheral NMDA expression occurs in patients with painful TMDs warrants further investigation.

Repeated oxytocin prevents central sensitization by regulating synaptic plasticity via oxytocin receptor in a chronic migraine mouse model

BackgroundCentral sensitization is one of the characters of chronic migraine (CM). Aberrant synaptic plasticity can induce central sensitization. Oxytocin (OT), which is a hypothalamic hormone, plays an important antinociceptive role. However, the antinociceptive effect of OT and the underlying mechanism in CM remains unclear. Therefore, we explored the effect of OT on central sensitization in CM and its implying mechanism, focusing on synaptic plasticity.MethodsA CM mouse model was established by repeated intraperitoneal injection of nitroglycerin (NTG). Von Frey filaments and radiant heat were used to measure the nociceptive threshold. Repeated intranasal OT and intraperitoneal L368,899, an oxytocin receptor (OTR) antagonist, were administered to investigate the effect of OT and the role of OTR. The expression of calcitonin gene-related peptide (CGRP) and c-fos were measured to assess central sensitization. N-methyl D-aspartate receptor subtype 2B (NR2B)-regulated synaptic-associated proteins and synaptic plasticity were explored by western blot (WB), transmission electron microscope (TEM), and Golgi-Cox staining.ResultsOur results showed that the OTR expression in the trigeminal nucleus caudalis (TNC) of CM mouse was significantly increased, and OTR was colocalized with the postsynaptic density protein 95 (PSD-95) in neurons. Repeated intranasal OT alleviated the NTG-induced hyperalgesia and prevented central sensitization in CM mouse. Additionally, the OT treatment inhibited the overexpression of phosphorylated NR2B and synaptic-associated proteins including PSD-95, synaptophysin-1 (syt-1), and synaptosomal-associated protein 25 (snap25) in the TNC of CM mouse and restored the abnormal synaptic structure. The protective effect of OT was prevented by L368,899. Furthermore, the expression of adenylyl cyclase 1 (AC1)/ protein kinase A (PKA)/ phosphorylation of cyclic adenosine monophosphate response element-binding protein (pCREB) pathway was depressed by OT and restored by L368,899.ConclusionsOur findings demonstrate that repeated intranasal OT eliminates central sensitization by regulating synaptic plasticity via OTR in CM. The effect of OT has closely associated with the down-regulation of AC1/PKA/pCREB signaling pathway, which is activated in CM model. Repeated intranasal OT may be a potential candidate for CM prevention.

Bidentatide, a Novel Plant Peptide Derived from Achyranthes bidentata Blume: Isolation, Characterization, and Neuroprotection through Inhibition of NR2B-Containing NMDA Receptors.

Increasing attention is being focused on the use of polypeptide-based N-methyl-d-aspartate (NMDA) receptor antagonists for the treatment of nervous system disorders. In our study on Achyranthes bidentata Blume, we identified an NMDA receptor subtype 2B (NR2B) antagonist that exerts distinct neuroprotective actions. This antagonist is a 33 amino acid peptide, named bidentatide, which contains three disulfide bridges that form a cysteine knot motif. We determined the neuroactive potential of bidentatide by evaluating its in vitro effects against NMDA-mediated excitotoxicity. The results showed that pretreating primary cultured hippocampal neurons with bidentatide prevented NMDA-induced cell death and apoptosis via multiple mechanisms that involved intracellular Ca2+ inhibition, NMDA current inhibition, and apoptosis-related protein expression regulation. These mechanisms were all dependent on bidentatide-induced inhibitory regulation of NR2B-containing NMDA receptors; thus, bidentatide may contribute to the development of neuroprotective agents that would likely possess the high selectivity and safety profiles inherent in peptide drugs.

Cattle connection: molecular epidemiology of BVDV outbreaks via rapid nanopore whole-genome sequencing of clinical samples

BackgroundAs a global ruminant pathogen, bovine viral diarrhea virus (BVDV) is responsible for the disease Bovine Viral Diarrhea with a variety of clinical presentations and severe economic losses worldwide. Classified within the Pestivirus genus, the species Pestivirus A and B (syn. BVDV-1, BVDV-2) are genetically differentiated into 21 BVDV-1 and four BVDV-2 subtypes. Commonly, the 5’ untranslated region and the Npro protein are utilized for subtyping. However, the genetic variability of BVDV leads to limitations in former studies analyzing genome fragments in comparison to a full-genome evaluation.ResultsTo enable rapid and accessible whole-genome sequencing of both BVDV-1 and BVDV-2 strains, nanopore sequencing of twelve representative BVDV samples was performed on amplicons derived through a tiling PCR procedure. Covering a multitude of subtypes (1b, 1d, 1f, 2a, 2c), sample matrices (plasma, EDTA blood and ear notch), viral loads (Cq-values 19–32) and species (cattle and sheep), ten of the twelve samples produced whole genomes, with two low titre samples presenting 96 % genome coverage.ConclusionsFurther phylogenetic analysis of the novel sequences emphasizes the necessity of whole-genome sequencing to identify novel strains and supplement lacking sequence information in public repositories. The proposed amplicon-based sequencing protocol allows rapid, inexpensive and accessible obtainment of complete BVDV genomes.

Focal cortical dysplasia type 1.

The ILAE classification of Focal Cortical Dysplasia (FCD) from 2011 has quickly gained acceptance in clinical practice and research and is now widely used around the world. This histopathology‐based classification scheme proposed three subtypes, that is, FCD Type 1 (with architectural abnormalities of the neocortex), FCD Type 2 (with cytoarchitectural abnormalities of the neocortex) and FCD Type 3 (architectural abnormalities of the neocortex associated with another principle lesion acquired during early life). Valuable knowledge was gathered during the last decade validating the clinical, pathological and genetic classification of FCD Type 2. This is in contrast to FCD subtype 1 and 3 with only few robust or new insights. Herein, we provide an overview about current knowledge about FCD Type 1 and its three subtypes. Available data strengthened, however, FCD Type 1A in particular, whereas a comprehensive clinico‐pathological specification for FCD Type 1B and 1C subtypes remain to be shown. The lack of a valid animal model for FCD Type 1 further supports our call and the ongoing need for systematic research studies based on a careful clinico‐pathological and genetic stratification of patients and human brain tissues.

Genotypic distribution of hepatitis C virus in Uttarakhand

PurposeHepatitis C virus is a major cause of chronic hepatitis with seven known genotypes. Uttarakhand is a north Indian state in the Sub-Himalayan region where the genotypic distribution of HCV is largely unknown. This study was undertaken in order to assess the pattern of genotype and subtype and understand the risk factors leading to transmission of Hepatitis C virus in this understudied region. MethodsAnti-HCV reactive cases were selected for determination of the circulating genotypes. Viral RNA was confirmed by real-time PCR. Strains were amplified and sequenced using Sanger's methods. Phylogenetic tree was constructed to determine the genotype. ResultsGenotype 3 was found to be the predominant genotype majority being subtype 3a and 3b followed by genotype 1. Subtypes 3g and genotype 4a were also observed. Major risk factor found was parenteral injection therapy from unregistered medical practitioners for minor ailments. ConclusionsFindings of our study will help in tailoring management and prevention protocols for HCV for the people of this region.

Reliability of the Penny and Beit CURE Radiologic Classifications of Pediatric Patients with Chronic Hematogenous Osteomyelitis in the Philippine General Hospital

Objective. This study aimed to evaluate the inter- and intraobserver reliability of the Penny and Beit CURE radiologic classifications of pediatric patients with Chronic Hematogenous Osteomyelitis (CHOM) in the Philippine General Hospital (PGH).&#x0D; Methods. Thirty-four pre-operative radiographs of PGH pediatric patients with CHOM were classified by seven orthopedic surgeons using both Penny and Beit CURE Classification systems. Two sets of radiographs were sent to the surgeons twice, four weeks apart, to classify. The Fleiss and Cohen κ statistics were used to determine inter- and intraobserver reliabilities, respectively.&#x0D; Results. The Penny Classification had a slight to fair interobserver reliability (Fleiss κ = 0.17 and 0.24) and a fair intraobserver reliability (Cohen κ =0.35) with a 49.58% average intraobserver agreement. The interobserver reliability when including all Beit CURE classification subtypes was fair (κ = 0.28 and 0.31). This improved to moderate (κ = 0.41 and 0.54) when using only the four main types of the Beit CURE classification with a 77.31% intraobserver agreement.&#x0D; Conclusion. The Beit CURE classification for pediatric CHOM had higher inter- and intraobserver agreement rates than the Penny classification. Further improvement in reliability can be made by combining B2 and B3 subtypes under the Beit CURE classification.

Significance of genotyping in the diagnosis of arthritis associated with C-viral hepatitis

To date, a number of studies have been conducted on the relationship of HCV genotypes with complications such as liver cirrhosis, hepatocellular carcinoma, but research on the correlation of the genotype with extrahepatic clinical manifestations associated with HCV, especially rheumatic manifestations, is insufficient. The purpose of the study is to analyze the most common genotypes of viral hepatitis C in the Republic of Uzbekistan and study their correlation with rheumatic manifestations of HCV. Methods: This study involved 88 patients with HCV infection who received inpatient and subsequent ambulatornoe treatment in Scientific Research Institute of Epidemiology, Microbiology and Infectious diseases of the Republic of Uzbekistan. Diagnostics procedures at the initial level included a set of studies, i. e. clinical, rheumatological and laboratory studies, ultrasound of the joint. In addition, 88 samples of RNA - positive serum from patients diagnosed with HCV were genotyped. Results: the Results showed that genotype 1 of HCV (subtype 1b) is the main genetic variant of HCV in Uzbekistan. Based on the results obtained, the genotypic features of viruses can be markers of the development of extrahepatic clinical manifestations. There is a reliable direct correlation between the incidence and severity of associated arthritis in patients with chronic viral hepatitis C with genotype 1b of the virus according to our research. Conclusions: The results of the study can be provided to help the doctor of the polyclinic service as recommendations that patients with the 1b genotype of the virus have a greater adherence to associated arthritis, and in this case, timely targeted consultation of a specialist is necessary.

Prevalence of HCV genotypes and subtypes in Southeast Asia: A systematic review and meta-analysis.

Known for its high genetic diversity and variation in genotypic presence in different regions of the world, hepatitis C virus (HCV) is estimated to infect about 71 million people globally. Selection of an appropriate therapeutic regimen largely depends on the identification of the genotype responsible for the infection. This systematic review and meta-analysis was conducted to provide a comprehensive view of HCV genotype and subtype distribution in Southeast Asia (SEA). The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). We searched five databases without year and language restrictions. Data from 90 eligible studies involving 15,089 genotypes and 9,646 subtypes representing 10 SEA countries were analyzed. The pooled estimates showed that genotype 1 (46.8%) [95% CI, 43.2–50.4; I2 = 92.77%; p < 0.001] was the most dominant HCV genotype in the region, followed by genotype 3 (23.1%) [95% CI, 19.4–27.2; I2 = 93.03%; p < 0.001], genotype 6 (16.5%) [95% CI, 13.8–19.6], genotype 2 (4.6%) [95% CI, 3.5–5.9], genotype 4 (1.1%) [95% CI, 0.7–1.5] and genotype 5 (0.8%) [95% CI, 0.4–1.3]. Philippines had the highest prevalence of genotypes 1 and 2. Genotype 6 became more prevalent after year 2000. Over 40 different subtypes were identified, with subtypes 1b (26.3%), 1a (21.3%), and 3a (14.3%) being the most prevalent of all the reported subtypes. Although on a global scale, genotype 6 is considered highly prevalent in SEA, evidence from this study reveals that it is the third most prevalent genotype within the region.

Synthesis and Analysis of Properties of an Immunogenic Fragment from NS4A Polypeptide of Hepatitis C Virus

—The work is aimed at the synthesis and analysis from NS4A of hepatitis C virus (HCV) antigen peptide fragment that contains a conserved B-cell and T-helper epitopes. The 24-mer peptide VIVGRIILSGRPAVIPDREVLYRK-NH2, which contains the main immunogenic site 24–46 of HCV NS4A antigen (corresponding to the 1681–1703 amino acid residues of the HCV polypeptide), subtype 1b, has been prepared via solid-phase synthesis according to the Fmoc-protocol. Particles with diameters of 73 ± 10 nm (30%) and 236 ± 5 nm (70%) have been detected in the water solution of the highly purified peptide (0.5 mg/mL) by dynamic light scattering. The polydispersity index of 0.377 ± 0.012 implies the existence of heterogeneity because of the aggregation of the peptide molecules. The ζ-potential of the peptide aggregates has been determined as 7.0 ± 0.5 mV by means of electrophoretic light scattering. These data confirm the possibility for the development of a nanoscale liposome form of the peptide preparation. Immunoreactivity of the synthesized highly purified peptide has been studied with the use of blood sera of patients with chronic hepatitis C. Antipeptide immunoglobulins G have been detected in 41.7% of serum samples. Thus, this peptide has been shown to reproduce at least one B-epitope, to which antibodies are raised during natural HCV infection. The synthesized 24-mer peptide is a promising candidate for further research and for use as a potential immunogen for the design of a nanoscale therapeutic immunogenic liposomal peptide composition with synthetic lipids as an adjuvant.

Brugada syndrome: current concepts and genetic background

Brugada syndrome (BrS) is a hereditary clinical-electrocardiographic arrhythmic entity with low worldwide prevalence. The syndrome is caused by changes in the structure and function of certain cardiac ion channels and reduced expression of Connexin 43 (Cx43) in the Right Ventricle (RV), predominantly in the Right Ventricular Outflow Tract (VSVD), causing electromechanical abnormalities. The diagnosis is based on the presence of spontaneous or medicated ST elevation, characterized by boost of the J point and the ST segment ≥2 mm, of superior convexity "hollow type" (subtype 1A) or descending rectilinear model (subtype 1B). BrS is associated with an increased risk of syncope, palpitations, chest pain, convulsions, difficulty in breathing (nocturnal agonal breathing) and/or Sudden Cardiac Death (SCD) secondary to PVT/VF, unexplained cardiac arrest or documented PVT/VF or Paroxysmal atrial fibrillation (AF) in the absence of apparent macroscopic or structural heart disease, electrolyte disturbance, use of certain medications or coronary heart disease and fever. In less than three decades since the discovery of Brugada syndrome, the concept of Mendelian heredity has come undone. The enormous variants and mutations found mean that we are still far from being able to concretely clarify a genotype-phenotype relationship. There is no doubt that the entity is oligogenetic, associated with environmental factors, and that there are variants of uncertain significance, especially the rare variants of the SCN5A mutation, with European or Japanese ancestors, as well as a spontaneous type 1 or induced pattern, thanks to gnomAD (coalition) researchers who seek to aggregate and harmonize exome and genome sequencing data from a variety of large scale sequencing projects and make summary data available to the scientific community at large). Thus, we believe that this in depth analytical study of the countless mutations attributed to BrS may constitute a real cornerstone that will help to better understand this intriguing syndrome.

RTMS alleviates cognitive and neural oscillatory deficits induced by hindlimb unloading in mice via maintaining balance between glutamatergic and GABAergic systems

Microgravity, as a part of the stress of space flight, has several negative effects on cognitive functions. Repetitive transcranial magnetic stimulation (rTMS), as a novel non-invasive technique, could be an effective approach to alleviated cognitive decline, applied in both preclinical and clinical studies. Neural oscillations and their interactions are involved in cognitive functions and support the communication of neural information. The neural oscillation could be a window from which we may understand what happens in the brain. The current study aimed to explore if 15 Hz rTMS plays a neural modulation role in a mouse model of hindlimb unloading. We hypothezed that rTMS can improve the cognitive and neural oscillatory deficits induced by hindlimb unloading via maintaining the balance between glutamatergic and GABAergic systems. Our data show that rTMS can significantly alleviate behavior deficits, modulate theta oscillation, improve the disturbed power distribution of theta oscillation and the decreased strength of Cross-Frequency Coupling in the dentate gyrus region, and effectively mitigated the blocked communication of neural information in the perforant pathway (PP)―dentate gyrus (DG) neural pathway in Hu mice. Furthermore, biochemical analysis using high-performance liquid chromatography and Western blot assay confirmed that rTMS increases the low expression of glutamate (Glu) and N-Methyl d-Aspartate receptor subtype 2B (NR2B) and decreases the high expression of γ-aminobutyric acid (GABA), 67 KDa isoform of glutamate decarboxylase (GAD67), and GABA type A receptor subunit alpha1 (GABAARα1) in the hippocampus of Hu mice. Taken together, the results suggest that rTMS plays a significant neural modulation role in the hippocampal neural activity disorders induced by Hu, which possibly depends on rTMS maintaining the balance of glutamatergic and gamma-aminobutyric acidergic (GABAergic) systems.