Molecular detection, risk factors, and phylogenetic analysis of tick-borne pathogens in dogs from northern Vietnam.

In tropical regions, numerous tick-borne pathogens (TBPs) play a crucial role as causative agents of infectious diseases in humans and animals. Recently, the population of companion and pet dogs has significantly increased in Vietnam; however, information on the occurrence of TBPs is still limited. The objectives of this investigation were to determine the occurrence rate, risk factors, and phylogenetic characteristics of TBPs in dogs from northern Vietnam. Of 341 blood samples tested by PCR, the total infection of TBPs was 73.9% (252/341). Babesia vogeli (18SrRNA gene - 30.5%) was detected most frequently in studied dogs followed by Rickettsia spp. (OmpA gene - 27%), Anaplasma platys (groEL gene - 22%), Bartonella spp. (16SrRNA - 18.8%), Mycoplasma haemocanis (16SrRNA - 9.4%) and Hepatozoon canis (18SrRNA gene - 1.2%), respectively. All samples were negative for Ehrlichia canis and Anaplasma phagocytophylum. Co-infection was detected in 31.4% of the samples (107/341) of which, A. platys/Bartonella spp. (34/94,10%), Rickettsia spp./B. vogeli (19/94, 5.6%), and M. haemocanis/B. vogeli (19/94, 5.6%) were recorded as the three most frequent two species of co-infection types. Statistical analysis revealed a significant correlation between TBP infection and several host variables regarding age, breed, and living area in the current study. The recent findings reported herein, for the first time in Vietnam, are essential for local veterinarians when considering the appropriate approaches for diagnosing these diseases. Furthermore, this data can be used to establish control measures for future surveillance and prevention strategies against canine TBPs in Vietnam.

Pulmonary function in patients with transfusion-dependent thalassemia and its associations with iron overload.

In patients with transfusion-dependent thalassemia (TDT), pulmonary function impairment has been reported but data are conflicting. Moreover, it remains unclear whether pulmonary dysfunction is associated with iron overload. This study aimed to evaluate the pulmonary function in patients with TDT and to investigate the associations between pulmonary dysfunction and iron overload. It was a retrospective observational study. 101 patients with TDT were recruited for lung function tests. The most recent ferritin levels (pmol/L) and the magnetic resonance imaging (MRI) measurements of the myocardial and liver iron status, as measured by heart and liver T2* relaxation time (millisecond, ms) respectively, were retrieved from the computerized medical records. Only data within 12 months from the lung function measurement were included in the analysis. The serum ferritin, and the cardiac and liver T2* relaxation time were the surrogate indexes of body iron content. The threshold of abnormality in lung function was defined as under 80% of the predicted value. 101 subjects were recruited with a mean age of 25.1 years (standard deviation (SD) 7.9 years). Thirty-eight (38%) and five (5%) demonstrated restrictive and obstructive lung function deficits, respectively. A weak correlation of FVC %Predicted and TLC %Predicted with MRI myocardial T2* relaxation time (rho = 0.32, p = 0.03 and rho = 0.33, p = 0.03 respectively) was observed. By logistic regression, MRI cardiac T2* relaxation time was negatively associated with restrictive lung function deficit (B - 0.06; SE 0.03; Odds ratio 0.94; 95% confidence interval (CI) 0.89-0.99; p = 0.023) after adjusting for age, sex and body mass index. Restrictive pulmonary function deficit was commonly observed in patients with TDT, and the severity potentially correlates with myocardial iron content. Monitoring of lung function in this group of patients, particularly for those with iron overload, is important.

Safety and immunogenicity of Nanocovax, a SARS-CoV-2 recombinant spike protein vaccine: Interim results of a double-blind, randomised controlled phase 1 and 2 trial.

Background: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminium hydroxide adjuvant. Methods: We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 mcg, 50 mcg, and 75 mcg doses, aluminium hydroxide adjuvanted (0·5 mg/dose) in 2-dose regime, 28 days apart (ClinicalTrials.gov number, NCT04683484). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2, 560 healthy adults received either vaccine doses similar in phase 1 (25 or 50 or 75 mcg S antigen in 0·5 mg aluminium per dose) or adjuvant (0·5 mg aluminium) in a ratio of 2:2:2:1. One primary outcome was the vaccine safety, including solicited adverse events for 7 day and unsolicited adverse events for 28 days after each injection as well as serious adverse event or adverse events of special interest throughout the study period. Another primary outcome was anti-S IgG antibody response (Index unit/ml). Secondary outcomes were surrogate virus neutralisation (inhibition percentage), wild-type SARS-CoV-2 neutralisation (dilution fold), and T-cell responses by intracellular staining for interferon gamma (IFNg). Anti-S IgG and neutralising antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients. Findings: For phase 1 study, no serious adverse events were observed for all 60 participants. Most adverse events were grade 1 and disappeared shortly after injection. For phase 2 study, after randomisation, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive the placebo (adjuvant only). Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups which reached their peaks at day 42 and declined afterward. At day 42, IgG levels of vaccine groups were 60·48 [CI95%: 51·12-71·55], 49·11 [41·26-58·46], 57·18 [48·4-67·5] compared to 7·10 [6·32-13·92] of convalescent samples. IgG levels reported here can be converted to WHO international standard binding antibody unit (BAU/ml) by multiplying them to a conversion factor of 21·8. Neutralising antibody titre of vaccine groups at day 42 were 89·2 [52·2-152·3], 80·0 [50·8-125.9] and 95·1 [63·1-143·6], compared to 55·1 [33·4-91·0] of the convalescent group. Interpretation: Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses. Funding: This work was funded by the Coalition for Epidemic Preparedness Innovations (CEPI), the Ministry of Science and Technology of Vietnam, and Nanogen Pharmaceutical Biotechnology JSC.

Prior infection with antigenically heterologous low pathogenic avian influenza viruses interferes with the lethality of the H5 highly pathogenic strain in domestic ducks.

Low and highly pathogenic avian influenza viruses (LPAIVs and HPAIVs, respectively) have been co-circulating in poultry populations in Asian, Middle Eastern, and African countries. In our avian-flu surveillance in Vietnamese domestic ducks, viral genes of LPAIV and HPAIV have been frequently detected in the same individual. To assess the influence of LPAIV on the pathogenicity of H5 HPAIV in domestic ducks, an experimental co-infection study was performed. One-week-old domestic ducks were inoculated intranasally and orally with phosphate-buffered saline (PBS) (control) or 106 EID50 of LPAIVs (A/duck/Vietnam/LBM678/2014 (H6N6) or A/Muscovy duck/Vietnam/LBM694/2014 (H9N2)). Seven days later, these ducks were inoculated with HPAIV (A/Muscovy duck/Vietnam/LBM808/2015 (H5N6)) in the same manner. The respective survival rates were 100% and 50% in ducks pre-infected with LBM694 or LBM678 strains and both higher than the survival of the control group (25%). The virus titers in oral/cloacal swabs of each LPAIV pre-inoculation group were significantly lower at 3-5 days post-HPAIV inoculation. Notably, almost no virus was detected in swabs from surviving individuals of the LBM678 pre-inoculation group. Antigenic cross-reactivity among the viruses was not observed in the neutralization test. These results suggest that pre-infection with LPAIV attenuates the pathogenicity of HPAIV in domestic ducks, which might be explained by innate and/or cell-mediated immunity induced by the initial infection with LPAIV.

Characterization of H3 subtype avian influenza viruses isolated from poultry in Vietnam.

To date, avian influenza viruses (AIVs) have persisted in domestic poultry in wet markets in East Asian countries. We have performed ongoing virus surveillance in poultry populations in Vietnam since 2011, with the goal of controlling avian influenza. Throughout this study, 110 H3 AIVs were isolated from 2760 swab samples of poultry in markets and duck farms. H3 hemagglutinin (HA) genes of the isolates were phylogenetically classified into eight groups (I-VIII). Genetic diversity was also observed in the other seven gene segments. Groups I-IV also included AIVs from wild waterbirds. The epidemic strains in poultry switched from groups I-III and VI to groups I, IV, V, and VIII around 2013. H3 AIVs in groups I and V were maintained in poultry until at least 2016, which likely accompanied their dissemination from the northern to the southern regions of Vietnam. Groups VI-VIII AIVs were antigenically distinct from the other groups. Some H3 AIV isolates had similar N6 neuraminidase and matrix genes as H5 highly pathogenic avian influenza viruses (HPAIVs). These results reveal that genetically and antigenically different H3 AIVs have been co-circulating in poultry in Vietnam. Poultry is usually reared outside in this country and is at risk of infection with wild waterbird-originating AIVs. In poultry flocks, the intruded H3 AIVs must have experienced antigenic drift/shift and genetic reassortment, which could contribute to the emergence of H5 HPAIVs with novel gene constellations.

Antiplatelet and Anticoagulant Use in Randomised Trials of Patients Undergoing Endovascular Intervention for Peripheral Arterial Disease: Systematic Review and Narrative Synthesis.

OBJECTIVE: Randomised trials of new devices for peripheral arterial endovascular intervention are published regularly. The evidence for which antiplatelet and/or anticoagulant (antithrombotic) therapy to use after an intervention is lacking. The aim of this systematic review was to examine the antithrombotic regimens in randomised trials for peripheral arterial endovascular intervention to understand choices made and trends with time or type of device. METHODS: Data sources were the Medline, Embase, and Cochrane Library databases. Randomised trials including participants with peripheral arterial disease undergoing any endovascular arterial intervention were included. Trial methods were assessed to determine whether an antithrombotic protocol had been specified, its completeness, and the agent(s) prescribed. Antithrombotic therapy protocols were classed as peri-procedural (preceding and during intervention), immediate post-procedural (up to 30 days following intervention), and maintenance post-procedural (therapy continuing beyond 30 days). RESULTS: Ninety-four trials were included in narrative synthesis. Study quality was low. None of the trials justified their antithrombotic therapy protocol. Only 29% of trials had complete peri-procedural antithrombotic protocols, and 34% had complete post-procedural protocols. In total, 64 different peri-procedural protocols, and 51 separate post-procedural protocols were specified. Antiplatelet monotherapy and unfractionated heparin were the most common regimen choices in the peri-procedural setting, and dual antiplatelet therapy (55%) was most commonly utilised post procedure. Over time there has been an increasing tendency to use dual therapy (p < .001). This corresponds with the introduction of newer technologies and trials focussed on below knee intervention. CONCLUSION: Randomised trials comparing different types of peripheral endovascular arterial intervention have a high level of heterogeneity in their antithrombotic regimens. Antiplatelet therapy needs to be standardised in trials comparing endovascular technologies to reduce potential confounding. To do this, an independent randomised trial specifically examining antiplatelet therapy following peripheral arterial endovascular intervention is needed.

High vitamin levels ameliorate negative effect of rapeseed meal in meat ducks by improving antioxidant activity.

The purpose of this study was to test the hypothesis that a high level of a vitamin premix would prevent the deleterious effects of rapeseed meal (RSM) when added to the diet of Pekin meat ducks. A total of 674 fifteen-day-old ducks were randomly allocated to 6 treatments with 7 cages of 16 ducks each. Three diets were formulated that contained 5, 10, or 20% RSM to compensate for reducing levels of soybean meal. Each RSM level diet was then supplemented with either a low level (low) or a high level (high) of a vitamin premix providing a total of 6 experimental diets. Ducks were fed one of the 6 experimental diets (N = 7 pens per diet) from days 15 to 35 at which time they were euthanized. Ducks were analyzed for antioxidant activity, liver biochemistry, thyroid hormone levels, and liver and thyroid histopathology. Addition of the high vitamin premixes to the 5 or 10% RSM diets improved BW (P < 0.05), BW gain (BWG; P < 0.05), and feed to gain ratio (F/G; P < 0.05) compared to the low vitamin premix; however, neither vitamin premix level had effects on production variables of ducks fed the 20% RSM diet. The high vitamin premix level also improved antioxidant capacity as evidenced by increased (P < 0.05) serum and liver superoxide dismutase activities over that of the low vitamin premix diets. Furthermore, the high level of vitamin premix prevented liver and thyroid pathologies in diets that contain RSM compared to diets with the low vitamin premix. These results suggested that high vitamin premix could prevent the negative effects of a 5 or 10% RSM diet in ducks by improving antioxidative capacities and alleviating liver and thyroid damage.

Silica Nanoparticle-induced Cytokine Responses in BEAS-2B and HBEC3-KT Cells: Significance of Particle Size and Signalling Pathways in Different Lung Cell Cultures.

We have previously reported that silica nanoparticles (SiNPs) of nominal size 50 nm (Si50) induce the pro-inflammatory cytokines CXCL8 and IL-6 in BEAS-2B cells, via mechanisms involving MAPK p38, TACE-mediated TGF-α release and the NF-κB pathway. In this study, we examined whether these findings are cell specific or might be extended to another epithelial lung cell model, HBEC3-KT, and also to SiNPs of a smaller size (nominal size of 10 nm; Si10). The TEM average size of Si10 and Si50 was 10.9 and 34.7 nm, respectively. The surface area (BET) of Si10 was three times higher than for Si50 per mass unit. With respect to hydrodynamic size (DLS), Si10 in exposure medium showed a higher z-average for the main peak than Si50, indicating more excessive agglomeration. Si10 strongly induced CXCL8 and IL-6, as assessed by ELISA and RT-PCR, and was markedly more potent than Si50, even when adjusted to equal surface area. Furthermore, Si10 was far more cytotoxic, measured as lactate dehydrogenase (LDH) release, than Si50 in both epithelial cell cultures. With respect to signalling pathways, Western analysis and experiments with and without inhibition of MAPK, TACE and NF-κB (synthetic inhibitors) revealed that p38-phosphorylation, TACE-mediated TGF-α release and NF-κB activation seem to be important triggering mechanisms for both Si50 and Si10 in the two different lung epithelial cell cultures. In conclusion, the identified signalling pathways are suggested to be important in inducing cytokine responses in different epithelial cell types and also for various sizes of silica nanoparticles.

The genotypes of Orientia tsutsugamushi, identified in scrub typhus patients in northern Vietnam.

Background: There are an estimated one million patients with scrub typhus in the Asia-Pacific region. There are few reports describing the incidence of scrub typhus in Vietnam. Methods: Blood samples collected from 63 patients clinically diagnosed as having scrub typhus from July 2015 to September 2016 were subjected to genotyping of Orientia tsutsugamushi. Results and Conclusions: Of these patients, 42 (67%) tested positive for O. tsutsugamushi, and the most common genotype was identified to be Karp (55%). Other genotypes, TA763, Gilliam type in Japan variant, and Kato were also found in 17%, 17% and 12% of patients, respectively. To better understand the epidemiological landscape of scrub typhus in Vietnam, a countrywide study is needed. Accession numbers: LC110330-LC110333, LC110336-LC110351 and LC214804-LC214825.

TDAG8 activation attenuates cerebral ischaemia-reperfusion injury via Akt signalling in rats.

BACKGROUND: T-cell death-associated gene 8 (TDAG8), a member of the proton-sensitive G-protein-coupled receptor (GPCR) class with an immune-specific expression profile, was recently shown to be expressed in the rat brain; however, its role in ischaemic stroke remains unknown. METHODS: We initially confirmed the time-dependent expression of TDAG8 in rat brain tissue after ischaemic stroke and reperfusion. Further evaluations were performed to increase TDAG8 expression 6h prior to middle cerebral artery occlusion (MCAO) by injecting a specific agonist, BTB09089, into the lateral ventricle to increase TDAG8 expression. Twenty-four hours before MCAO, a specific small interfering RNA (siRNA) was introduced. The infarction volume, neurological deficit score and cleaved caspase-3 and Bcl-2 expression were used to assess the effects of TDAG8 on ischaemic stroke. Finally, the effects of TDAG8 on the development of primary cortical neurons exposed to oxygen-glucose deprivation (OGD) were investigated. RESULTS: TDAG8 expression increased both in vivo and in vitro. Pretreatment with BTB09089 up-regulated TDAG8 and Bcl-2 expression and down-regulated cleaved caspase-3 expression, while the infarction volume was reduced, and neurological deficits were ameliorated 24 and 72h after MCAO. However, the protective effects of TDAG8 were reversed when its level was reduced in TDAG8-deficient rats. More importantly, these findings are consistent with data from neurons subjected to OGD. CONCLUSIONS: TDAG8 plays an important neuroprotective role through inhibition of neuronal apoptosis and alleviation of neurological deficits by activating the Akt signalling pathway in rats.

Prevalence and Phylogenetic Analysis of Orientia tsutsugamushi in Small Mammals in Hanoi, Vietnam.

Rodents are important reservoirs of many human pathogens transmitted via arthropod vectors. Arthropod-borne bacteria belonging to the family Rickettsiaceae cause acute febrile diseases in humans worldwide, but the real burdens of rickettsial diseases appear to be underestimated in Hanoi, Vietnam, because differential diagnosis on the basis of clinical signs and symptoms is confounded by the presence of other tropical infectious diseases with similar signs and symptoms. To know the prevalence of bacteria of the family Rickettsiaceae among small mammals in Hanoi, 519 animals thriving in the public places were captured and examined for the presence of bacterial sequences using duplex PCR. Nucleotide sequences specific for Orientia tsutsugamushi were detected in seven samples (1.3%). Out of seven animals, two were captured in a market, whereas five were in hospitals. None of the captured small mammals tested positive for the genus Rickettsia. The nucleotide sequence analysis of the genes encoding the 47-kDa high-temperature requirement A (47-kDa HtrA) and 56-kDa type-specific antigen (TSA) showed that these seven isolates were indistinguishable from each other. O. tsutsugamushi isolated in this study was closely related phylogenetically to the Gilliam strain, which was originally isolated at the border of Assam and Burma, rather than to those isolated in the central to southern part of Vietnam. It should be emphasized that Vietnamese hospitals were heavily infested by small rodents and some of them harbored O. tsutsugamushi. Strict hygienic control should be implemented to mitigate the potential risk posed by O. tsutsugamushi in hospital settings.

Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA damage-response pathway in SCA3.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an untreatable autosomal dominant neurodegenerative disease, and the most common such inherited ataxia worldwide. The mutation in SCA3 is the expansion of a polymorphic CAG tri-nucleotide repeat sequence in the C-terminal coding region of the ATXN3 gene at chromosomal locus 14q32.1. The mutant ATXN3 protein encoding expanded glutamine (polyQ) sequences interacts with multiple proteins in vivo, and is deposited as aggregates in the SCA3 brain. A large body of literature suggests that the loss of function of the native ATNX3-interacting proteins that are deposited in the polyQ aggregates contributes to cellular toxicity, systemic neurodegeneration and the pathogenic mechanism in SCA3. Nonetheless, a significant understanding of the disease etiology of SCA3, the molecular mechanism by which the polyQ expansions in the mutant ATXN3 induce neurodegeneration in SCA3 has remained elusive. In the present study, we show that the essential DNA strand break repair enzyme PNKP (polynucleotide kinase 3'-phosphatase) interacts with, and is inactivated by, the mutant ATXN3, resulting in inefficient DNA repair, persistent accumulation of DNA damage/strand breaks, and subsequent chronic activation of the DNA damage-response ataxia telangiectasia-mutated (ATM) signaling pathway in SCA3. We report that persistent accumulation of DNA damage/strand breaks and chronic activation of the serine/threonine kinase ATM and the downstream p53 and protein kinase C-δ pro-apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in SCA3. Either PNKP overexpression or pharmacological inhibition of ATM dramatically blocked mutant ATXN3-mediated cell death. Discovery of the mechanism by which mutant ATXN3 induces DNA damage and amplifies the pro-death signaling pathways provides a molecular basis for neurodegeneration due to PNKP inactivation in SCA3, and for the first time offers a possible approach to treatment.

Remifentanil requirements for preventing motor response to skin incision in healthy women anesthetized with combinations of propofol and dexmedetomidine titrated to similar Bispectral Index (BIS) values.

BACKGROUND: It is unclear whether the sedative, analgesic or sympatholytic effects of adjunctive dexmedetomidine contribute to reduced analgesic requirements in general anesthesia. This study aimed to assess the analgesic effect of dexmedetomidine on intraoperative opioid requirements using body movement as observation indicator at similar BIS-guided sedative depth in propofol anesthesia. METHODS: Ninety patients were randomly divided into three groups to receive administration of saline, and dexmedetomidine at 0.5 and 1.0 µg kg(-1) over 10 min, followed by saline and dexmedetomidine at infusion rates of 0.17 and 0.33 µg kg(-1) h(-1), respectively. After dexmedetomidine and saline bolus administration, propofol was titrated to maintain the BIS values at 45-55. When BIS values reached the predetermined range, remifentanil was administered by target-controlled infusion. Five minutes following remifentanil treatment, skin was incised and the motor response observed. Then, the concentration of remifentanil blunting the motor response in 50% of patients (Ce50) was determined using a modified Dixon's sequential 'up-and-down' method. RESULTS: Dexmedetomidine significantly decreased effect-site concentrations of propofol for maintaining the preset BIS range (P < 0.01). The Ce50 (95% CI) of remifentanil were 0.93 (0.82-1.03), 1.03 (0.89-1.17) and 0.91 (0.77-1.06) ng ml(-1) in the 0 (saline), 0.5 and 1.0 µg kg(-1) dexmedetomidine groups, respectively, indicating non-statistically significant differences among groups (P > 0.0167). CONCLUSIONS: Propofol and its combination with dexmedetomidine have similar opioid requirements for preventing motor response to skin incision when titrated to similar BIS values. These findings indicate that adjunctive dexmedetomidine for general anesthesia has sedative but no opioid sparing effects.

Bacillus subtilis spores expressing the VP28 antigen: a potential oral treatment to protect Litopenaeus vannamei against white spot syndrome.

The envelope protein VP28 of white spot syndrome virus (WSSV) is considered a candidate antigen for use in a potential vaccine to this important shrimp pathogen (the cause of white spot syndrome, WSS). Here, we used spores of Bacillus subtilis to display VP28 on the spore surface. Trials were conducted to evaluate their ability to protect shrimps against WSSV infection. The gene cotB-vp28 was integrated into the chromosome of the laboratory strain B. subtilis PY79, and expression of CotB-VP28 was detected by Western blotting and immunofluorescence. Expression of CotB-VP28 was equivalent to 1000 molecules per spore. PY79 and CotB-VP28 spores were mixed with pellets for feeding of whiteleg shrimps (Litopenaeus vannamei), followed by WSSV challenge. Superoxidase dismutase (SOD), phenoloxidase activities and mortality rates of the two shrimp groups were evaluated. Groups fed with PY79 and CotB-VP28 spores at day 7 had increased SOD activities of 29% and increased phenoloxidase activities of 15% and 33%, respectively, compared to those of the control group. Fourteen days postchallenge, 35% of vaccinated shrimps had died compared to 49% of those fed naked spores (PY79) and 66% untreated, unchallenged animals. These data suggest that spores expressing VP28 have potential as a prophylactic treatment of WSS.

Development of a sensitive novel diagnostic kit for the highly pathogenic avian influenza A (H5N1) virus.

BACKGROUND: Sporadic emergence of the highly pathogenic avian influenza (HPAI) H5N1 virus infection in humans is a serious concern because of the potential for a pandemic. Conventional or quantitative RT-PCR is the standard laboratory test to detect viral influenza infections. However, this technology requires well-equipped laboratories and highly trained personnel. A rapid, sensitive, and specific alternative screening method is needed. METHODS: By a luminescence-linked enzyme immunoassay, we have developed a H5N1 HPAI virus detection kit using anti-H5 hemagglutinin monoclonal antibodies in combination with the detection of a universal NP antigen of the type A influenza virus. The process takes 15 minutes by use of the fully automated luminescence analyzer, POCube. RESUTLS: We tested this H5/A kit using 19 clinical specimens from 13 patients stored in Vietnam who were infected with clade 1.1 or clade 2.3.4 H5N1 HPAI virus. Approximately 80% of clinical specimens were H5-positive using the POCube system, whereas only 10% of the H5-positive samples were detected as influenza A-positive by an immunochromatography-based rapid diagnostic kit. CONCLUSIONS: This novel H5/A kit using POCube is served as a rapid and sensitive screening test for H5N1 HPAI virus infection in humans.

The risk of placental abruption and placenta previa in pregnant women with chronic hepatitis B viral infection: a systematic review and meta-analysis.

INTRODUCTION: Several epidemiological studies have found a positive association between chronic hepatitis B virus (CHB) infection and the risk of placental abruption and placenta previa, but various studies have reported conflicting findings. The objective was to systematically review the literature to determine a possible association between CHB infection and these two placental complications. METHODS: We conducted a computerized search in electronic database through March 1, 2014, supplemented with a manual search of reference lists, to identify original published research on placental abruption and placenta previa rates in women with CHB infection. Data were independently extracted, and relative risks were calculated. The meta-analysis was performed using Stata version 10.0 software. RESULTS: Five studies involving 9088 placenta previa cases were identified. No significant association between CHB infection and placenta previa was identified (OR = 0.98, 95% CI = 0.60-1.62). Five studies involving 15571 placental abruption cases were identified. No significant association between CHB infection and placental abruption was identified (OR = 1.42, 95% CI, 0.93-2.15). DISCUSSION: The immune response against the virus represents a key factor in determining infection outcomes. No observation of significant increased risk of the placental complications could be partially explained by the complex immune response during CHB infection. CONCLUSIONS: Our meta-analysis found no evidence of significant associations between CHB infection and increased risk of placental abruption as well as placenta previa. Further well-designed studies were warranted to assess any potential association between CHB infection and increased risk of placental abruption as well as placenta previa.

Advanced glycation end products as an upstream molecule triggers ROS-induced sFlt-1 production in extravillous trophoblasts: a novel bridge between oxidative stress and preeclampsia.

Although abnormal soluble fms-like tyrosine kinase-1 (sFlt-1) production is thought to be an important factor in the pathogenesis of pre-eclampsia, the mechanisms that regulate the production of sFlt-1 during pre-eclampsia are unclear. Accumulation of advanced glycation end products (AGEs) is prevalent in obesity, advanced maternal age, diabetes mellitus, and polycystic ovary syndrome. Alterations in the regulation and signaling of angiogenic pathways have been considered as a link between these conditions and pre-eclampsia. The purpose of this study was to explore the possible effects of AGEs on sFlt-1 secretion in extravillous trophoblasts (EVT). A EVT cell line (HRT-8/SVneo) was treated with various concentrations of AGEs-BSA. The mRNA expression of sFlt-1, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) in EVT were detected with real-time polymerase chain reaction. The secretion of sFlt-1, VEGF, and PlGF protein from EVT was measured with ELISA. The levels of intracellular reactive oxygen species (ROS) production were determined by DCFH-DA. Exposure of EVT to AGEs-BSA induced increased intracellular ROS generation and overexpression of sFlt-1 at mRNA and protein levels in a dose dependent manner. Anti-RAGE immunoglobulin G or apocynin (an inhibitors of NADPH oxidase) could decrease the intracellular ROS generation and subsequently suppressed the production of sFlt-1 at mRNA and protein levels. Our data suggested that AGEs may be a new class of important mediator in the regulation of angiogenic pathways of EVT. Accumulation of AGEs might contribute to the pathogenesis of preeclampsia by promoting sFlt-1 production through activation of RAGE/NADPH oxidase dependent pathway in EVT.

Antibody survey on avian influenza viruses using egg yolks of ducks in Hanoi between 2010 and 2012.

In Vietnam, numerous surveillance programs are conducted to monitor the prevalence of avian influenza (AI) viruses. Three serological methods-the agar-gel immunodiffusion test, hemagglutination inhibition (HI) test, and enzyme-linked immunosorbent assay-are well established for detection of AI virus antibodies in poultry sera. Several recent reports have validated egg yolk as an alternative source for detection of AI virus antibodies. In this study, we investigated AI virus antibodies in ducks by HI testing using egg yolk. Ten duck eggs were collected every month from 10 randomly selected markets in Hanoi from April 2010 to March 2012. The HI test was performed using low pathogenic avian influenza (LPAI) viruses (H3, H4, H6, H7, H9, and H11 subtypes) and highly pathogenic avian influenza (HPAI) viruses (H5N1 clade 2.3.4 and 2.3.2.1) as antigens. HI testing for H3, H6, and H9 was 29% positive in November 2010, 50% positive in October and November 2010, and 12% positive in June 2011. These results indicated that several epidemics of LPAI viruses had occurred during the study period. In addition, antibodies against H7 were negative. The results of HI testing for H5N1 showed that the reactivity of the dominant HI antibody shifted from H5N1 clade 2.3.4 to clade 2.3.2.1. In conclusion, egg yolk is useful for long term monitoring of AI virus antibodies and the use of egg-based antibody detection may contribute to improvements in animal welfare.

Effect of clopidogrel with or without omeprazole in patients with carotid artery stenting / Efecto del clopidogrel con o sin omeprazol en pacientes con stent en la arteria carótida

BACKGROUND: Recent concerns have been raised about the potential for proton pump inhibitors (PPIs) to blunt the efficacy of clopidogrel. We observed the effect of clopidogrel plus aspirin with or without omeprazole in patients with carotid stenoses after they received placement of carotid stents. METHODS: Sixty-four consecutive patients treated with percutaneous carotid artery stenting (CAS) comprised the sample. All enrolled patients underwent the C13 urea breath test (C13 UBT) before CAS. Patients with Helicobacter pylori infection and a history of peptic ulcer were assigned dual antiplatelet combination with omeprazole. Others received dual antiplatelet without omeprazole. Transcranial Doppler and ultrasonography were performed to assess the middle cerebral artery and carotid artery in follow-up at three months and six months. RESULTS: Eight patients had gastrointestinal bleeding; the event rate was 22.6% without omeprazole and 3.8% with omeprazole. The rate of gastrointestinal bleeding was reduced with omeprazole as compared without omeprazole (p = 0.026, p < 0.05). The two groups did not differ significantly in the rate of instent restenosis and thrombus through transcranial Doppler and ultrasonography. CONCLUSION: Among patients receiving dual antiplatelet therapy, prophylactic use of omeprazole reduced the rate of upper gastrointestinal bleeding. There was no apparent interaction between clopidogrel and omeprazole in patients with carotid artery stenting.

ANTECEDENTES: Recientemente se han expresado preocupaciones acerca de la posibilidad de que los inhibidores de la bomba de protones (IBP) para debilitar la eficacia del clopidogrel. Observamos el efecto del clopidogrel más aspirina con o sin omeprazol en pacientes con estenosis de la arteria carótida después de que recibieran la colocación de stents carotídeos. MÉTODOS: Sesenta y cuatro pacientes consecutivos tratados con stent percutáneo de la arteria carótida (SAC) fueron seleccionados para formar la muestra. A todos los pacientes inscritos se les realizó la prueba de aliento con urea C13 (C13 UBT) antes de CAS. A pacientes con infección por Helicobacter pylori y antecedentes de úlcera péptica les fue asignada una combinación antiplaquetaria dual con omeprazol. Otros recibieron tratamiento antiplaquetario dual sin omeprazol. Se realizaron una prueba Transcranial Doppler y una ultrasonografía a fin de evaluar la arteria cerebral media y la arteria carótida en seguimientos a los tres meses y a los seis meses. RESULTADOS: Ocho pacientes tuvieron hemorragia gastrointerstinal; la tasa de eventos fue 22.6% sin omeprazol y 3.8% con omeprazol. La tasa de hemorragia gastrointerstinal se redujo con omeprazol en comparación con la obtenida sin omeprazol (p = 0,026, p < 0.05). Los dos grupos no difirieron significativamente con respecto a la tasa de restenosis en stent y trombos a través de la prueba Transcranial Doppler y la ultrasonografía. CONCLUSIÓN: Entre los pacientes que reciben terapia antiplaquetaria dual, el uso profiláctico de omeprazol redujo la tasa de hemorragia gastrointestinal superior. No hubo interacción ostensible entre el clopidogrel y el omeprazol en pacientes con stent de la arteria carótida.

The genetic match between vaccine strains and circulating seasonal influenza A viruses in Vietnam, 2001-2009.

BACKGROUND: Vietnam is currently developing domestic capability to manufacture influenza vaccines but information on the genetic and antigenic characteristics of locally circulating seasonal influenza viruses is limited. To assess the relevance of WHO recommended vaccine strains to the situation in Vietnam, we analyzed the genetic relatedness of the hemagglutinin (HA) gene of seasonal influenza A viruses circulating in Vietnam from 2001 to 2009 to WHO recommended vaccine strains over the same period. METHODS AND PRINCIPAL FINDINGS: We sequenced the HA gene of 32 H1N1 and 44 H3N2 seasonal influenza A isolates from laboratory-based sentinel surveillance sites in Hanoi from 2001 to 2005 and from a national influenza surveillance system from 2005 to 2009. H1 and H3 HA phylogenetic trees rooted to vaccine strains A/Beijing/295/1995 (H1N1) and A/Moscow/10/1999 (H3N2), respectively, were constructed with contemporary HA sequences of isolates from neighboring countries. We found some genetic differences between seasonal influenza H3N2 viruses and three WHO influenza vaccine strains recommended for use in the Northern and Southern Hemispheres for the 2001-2004 and 2007-2008 seasons and close genetic identity of circulating H3N2 strains with the recommended WHO Southern Hemisphere vaccine strains for 2004 and 2009 seasons. The genetic similarity of circulating H1N1 strains with the WHO recommended vaccine strains are described for the study period 2001-2009. CONCLUSIONS: The HA gene of seasonal influenza virus strains in Vietnam (especially influenza A/H3N2) showed varying degrees of genetic identity compared with those of the Northern or Southern Hemisphere vaccine strains recommended by WHO. The close relatedness of the HA of Vietnamese strains and contemporary strains from nearby countries indicate a good genetic match of circulating strains during study period. Greater representation of virus isolates from South East Asia in the vaccine strain selection process is desirable of influenza vaccine development in Vietnam.