Safety and immunogenicity of two formulations of rotavirus vaccine in Vietnamese infants.

BACKGROUND AND AIMS: ROTAVIN-M1® (licensed, frozen vaccine) and ROTAVIN (second-generation, liquid candidate vaccine) are two rotavirus vaccine formulations developed from a live attenuated G1P8 (KH0118) strain by Center for Research and Production of Vaccines and Biologicals (POLYVAC), Vietnam. This study compared the safety and immunogenicity of these two formulations. METHODS: A Phase 3, randomized, partially double-blinded, active-controlled study was conducted in healthy infants aged 60-91 days in Vietnam. Infants received two doses of ROTAVIN or ROTAVIN-M1 in a ratio of 2:1 with an interval of 8 weeks. Solicited reactions were collected for 7 days after each vaccination. Blood samples were collected pre-vaccination and 4 weeks after the second vaccination in a subset of infants. Non-inferiority criteria required that the lower bound of 95% confidence intervals (CIs) of the post-vaccination anti-rotavirus IgA GMC (Geometric Mean Concentration) ratio of ROTAVIN/ROTAVIN-M1 should be >0.5. A co-primary objective was to compare the safety of the two vaccines in terms of solicited reactions. RESULTS: A total of 825 infants were enrolled. The post-vaccination GMC was 48.25 (95% CI: 40.59, 57.37) in the ROTAVIN group and 35.04 (95% CI: 27.34, 44.91) in the ROTAVIN-M1 group with an IgA GMC ratio of 1.38 (95% CI: 1.02, 1.86) thus meeting the pre-set criteria for non-inferiority. A total of 605 solicited reactions were reported in 297 (36.0%) participants with 35.4% in the ROTAVIN group and 37.2% in the ROTAVIN-M1 group. There were no cases of intussusception or death reported in the study. CONCLUSIONS: Based on the data generated, it can be concluded that ROTAVIN is immunologically non-inferior and has similar safety profile to ROTAVIN-M1 when administered to infants in a two-dose schedule. Therefore, it can be considered as a more suitable option for programmatic use to prevent rotavirus diarrhoea in Vietnam and the Mekong region. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT03703336, October 11, 2018.

PHO1 family members transport phosphate from infected nodule cells to bacteroids in Medicago truncatula.

Legumes play an important role in the soil nitrogen availability via symbiotic nitrogen fixation (SNF). Phosphate (Pi) deficiency severely impacts SNF because of the high Pi requirement of symbiosis. Whereas PHT1 transporters are involved in Pi uptake into nodules, it is unknown how Pi is transferred from the plant infected cells to nitrogen-fixing bacteroids. We hypothesized that Medicago truncatula genes homologous to Arabidopsis PHO1, encoding a vascular apoplastic Pi exporter, are involved in Pi transfer to bacteroids. Among the seven MtPHO1 genes present in M. truncatula, we found that two genes, namely MtPHO1.1 and MtPHO1.2, were broadly expressed across the various nodule zones in addition to the root vascular system. Expressions of MtPHO1.1 and MtPHO1.2 in Nicotiana benthamiana mediated specific Pi export. Plants with nodule-specific downregulation of both MtPHO1.1 and MtPHO1.2 were generated by RNA interference (RNAi) to examine their roles in nodule Pi homeostasis. Nodules of RNAi plants had lower Pi content and a three-fold reduction in SNF, resulting in reduced shoot growth. Whereas the rate of 33Pi uptake into nodules of RNAi plants was similar to control, transfer of 33Pi from nodule cells into bacteroids was reduced and bacteroids activated their Pi-deficiency response. Our results implicate plant MtPHO1 genes in bacteroid Pi homeostasis and SNF via the transfer of Pi from nodule infected cells to bacteroids.

Optimization and application of MTT assay in determining density of suspension cells.

MTT assay has been applied widely in stimulation and inhibition tests for adherent cells. However, reading step in regular MTT assays requires medium removal to dissolve formazan by absolute solvents results are usually affected by incomplete formazan dissolution and protein precipitation in diluted solvents. Therefore, most of current MTT assay procedures have difficulties in application on suspension cell lines. In this study, we demonstrated a modified MTT assay in which formazan dissolution method was improved by using the combination of DMSO and SDS-lysis solution. Importantly, the modified MTT assay did not require medium removal, thus it can be applicable for both suspension and adherent cell lines. We also verified that the modified MTT procedure could be effectively applied in bioactivity assays such as cancer cell inhibition and fibroblast stimulation assays. Besides the ease of use, our data regarding nonlinear regression model fitting, data variation, and separation clearly demonstrated that the sensitivity, stability and precision of modified assay were higher than those of common MTT procedures using isopropanol or DMSO as solvents. This study indicated that the modification described here can broaden the MTT assay application on suspension cell lines and also simplify the MTT protocol on adherent cell lines.

Evolutionary tinkering of the expression of PDF1s suggests their joint effect on zinc tolerance and the response to pathogen attack.

Multigenic families of Plant Defensin type 1 (PDF1) have been described in several species, including the model plant Arabidopsis thaliana as well as zinc tolerant and hyperaccumulator A. halleri. In A. thaliana, PDF1 transcripts (AtPDF1) accumulate in response to pathogen attack following synergic activation of ethylene/jasmonate pathways. However, in A. halleri, PDF1 transcripts (AhPDF1) are constitutively highly accumulated. Through an evolutionary approach, we investigated the possibility of A. halleri or A. thaliana species specialization in different PDF1s in conveying zinc tolerance and/or the response to pathogen attack via activation of the jasmonate (JA) signaling pathway. The accumulation of each PDF1 from both A. halleri and A. thaliana was thus compared in response to zinc excess and MeJA application. In both species, PDF1 paralogues were barely or not at all responsive to zinc. However, regarding the PDF1 response to JA signaling activation, A. thaliana had a higher number of PDF1s responding to JA signaling activation. Remarkably, in A. thaliana, a slight but significant increase in zinc tolerance was correlated with activation of the JA signaling pathway. In addition, A. halleri was found to be more tolerant to the necrotrophic pathogen Botrytis cinerea than A. thaliana. Since PDF1s are known to be promiscuous antifungal proteins able to convey zinc tolerance, we propose, on the basis of the findings of this study, that high constitutive PDF1 transcript accumulation in A. halleri is a potential way to skip the JA signaling activation step required to increase the PDF1 transcript level in the A. thaliana model species. This could ultimately represent an adaptive evolutionary process that would promote a PDF1 joint effect on both zinc tolerance and the response to pathogens in the A. halleri extremophile species.

Rhizobacterially induced protection of watermelon against Didymella bryoniae.

AIMS: To identify rhizobacteria from the Mekong Delta of Vietnam, which can systemically protect watermelon against Didymella bryoniae and elucidate the mechanisms involved in the protection conferred by isolate Pseudomonas aeruginosa 23(1-1). METHODS AND RESULTS: Bacteria were isolated from watermelon roots and their antagonistic ability tested in vitro. Of 190 strains, 68 were able to inhibit D. bryoniae by production of antibiotics. Four strains were able to reduce foliar infection by D. bryoniae when applied to watermelon seeds before sowing. Strain Ps. aeruginosa 23(1-1) was chosen for investigations of the mechanisms involved in protection and ability to control disease under field conditions. In the field, the bacterium was able to significantly reduce disease in two consecutive seasons and increase yield. Furthermore, it colonized watermelon plants endophytically, with higher numbers in plants infected by D. bryoniae than in noninoculated plants. To elucidate the mechanisms involved in protection, the infection biology of the pathogen was studied in bacterially treated and control plants. Pseudomonas aeruginosa 23(1-1) treatment inhibited pathogen penetration and this was associated with hydrogen peroxide accumulation, increased peroxidase activity and occurrence of new peroxidase isoforms, thus indicating that resistance was induced. CONCLUSIONS: The endophytic bacterium Ps. aeruginosa 23(1-1) can control D. bryoniae in watermelon by antibiosis and induced resistance under greenhouse and field conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings suggest that rhizobacteria from native soils in Vietnam can be used to control gummy stem blight of watermelon through various mechanisms including induction of resistance.

Identification of genes for resistance to a Digitaria isolate of Magnaporthe grisea in common wheat cultivars.

Common wheat cultivars are resistant to Magnaporthe grisea, a crabgrass (Digitaria sanguinalis)-specific species of the blast fungus. To dissect the genetic basis of this "nonhost" type of resistance, we need an exceptional cultivar that is susceptible to M. grisea. A screening under various conditions revealed that Triticum aestivum 'Chinese Spring' (CS) was susceptible to M. grisea isolate Dig41 when incubated at high temperature (26 degrees C) after inoculation. By contrast, T. aestivum 'P168', 'Shin-chunaga' (Sch), 'Norin 4' (N4), 'Norin 26' (N26), 'Norin 29' (N29), 'Red Egyptian' (RE), and 'Salmon' (Slm) and Triticum compactum 'No. 44' (Cmp) were highly resistant even at the high temperature. When F2 seedlings derived from crosses between the resistant cultivars and CS were inoculated with Dig41, they segregated in a 3:1 ratio of resistant to susceptible, suggesting that the resistance of each cultivar is controlled by one major gene. Crosses of N4 with P168, Sch, N26, N29, and Cmp yielded no susceptible F2 seedlings, suggesting that these six cultivars share the same gene. Similarly, a cross between RE and Slm yielded no susceptible F2 seedlings, suggesting that these two cultivars share the same gene. On the other hand, crosses between the N4 group and the RE group produced resistant and susceptible seedlings in a 15:1 ratio, indicating that these two groups carry different genes inherited independently. The gene in N4 was located on chromosome 4A by a monosomic analysis and designated Rmg4, while the gene in RE was located on chromosome 6D using a series of chromosome substitution lines and designated Rmg5. These results suggest that the resistance of common wheat to M. grisea, an inappropriate species of the blast fungus, is under a simple genetic control.

Delivery care utilisation and care-seeking in the neonatal period: a population-based study in Vietnam.

BACKGROUND: If millions of neonatal deaths each year are to be prevented, one crucial component that must be improved is adequate care-seeking behaviour and effective use of existing health care systems. We have investigated these factors in relation to delivery and the neonatal period in a province in Northern Vietnam, a setting currently in socio-economic transition. METHODS: Information on births and neonatal deaths between January and December 2005 in Quang Ninh province was collected. Narratives of the neonatal deaths were gathered and information about care-seeking in relation to delivery and illness was extracted. This information was then compared with the time and place of delivery and death. RESULTS: We registered 17,519 births and 284 neonatal deaths occurring between January and December 2005. The neonatal mortality rate varied from 7.5/1000 to 38/1000, depending on the place of delivery. A quarter of the neonatal deaths had no contact with the health-care system at the time of death. Neonatal death within 24 hours of birth was more likely when the mother did not seek care at the time of delivery, or did so at the lowest level of the system (chi2=35.5, p<0.001). Mothers of ethnic minorities were more likely to exhibit this care-seeking behaviour at delivery. CONCLUSION: Further improvement in neonatal survival can be achieved by changes in health system utilisation that aim to secure safe delivery for pregnant women. More efforts at local level are needed to encourage adequate care-seeking.

Predicting the clinical outcome of tetanus: the tetanus severity score.

OBJECTIVES: To create a new tetanus score and compare it with the Phillips and Dakar scores. METHODS: We used prospectively acquired data from consecutive patients admitted to the Hospital for Tropical Diseases, Ho Chi Minh City, to create the Tetanus Severity Score (TSS) with multivariate logistic regression. We compared the new score with Phillips and Dakar scores by means of resubstituted and prospective data, assessing performance in terms of sensitivity, specificity and area under receiver operator characteristic curves. RESULTS: Resubstitution testing yielded a sensitivity of 77% (298/385) and a specificity of 82% (1,183/1,437) for the TSS; 89% (342/385) and 20% (281/1,437) for the Phillips score; and 13% (49/385) and 98% (1,415/1,437) for the Dakar score. The TSS showed greatest discrimination with 0.89 area under the receiver operator characteristic curve (95% CI 0.88-0.90); this was 0.74 for the Dakar score and (95% CI 0.71-0.77) and 0.66 for the Phillips score (95% CI 0.63-0.70; P values <0.001). Prospective testing showed 65% (13/20) sensitivity and 91% (210/230) specificity for the TSS; 80% (16/20) and 51% (118/230) for the Phillips score; and 25% (5/20) and 96% (221/230) for the Dakar score. The TSS achieved the greatest area under TSS of 0.89 (95% CI 0.82-0.96), significantly greater than the Phillips score [0.74 (0.6-0.88), P = 0.049] but not the Dakar score [0.80, (0.71-0.90), P = 0.090]. CONCLUSIONS: The TSS is the first prospectively developed classification scheme for tetanus and should be adopted to aid clinical triage and management and as a basis for clinical research.

Distribution of molar mass and branching index of natural rubber from Hevea brasiliensis trees of different age by size exclusion chromatography coupled with online viscometry.

Natural rubber from hevea brasiliensis trees (Thailand, RRIM 600 clone) of different age (8, 20, and 35 years) were characterized by size exclusion chromatography coupled with online viscometry according to their distribution of molar mass and branching index at a temperature of 70 degrees C using cyclohexane as solvent. Washing with an aqueous solution of sodium dodecylsulfate and subsequent saponification purified the natural rubber samples. With this procedure physical branching points caused by phospholipids, proteins and hydrophobic terminal units, mainly fatty acids, of the natural rubber (cis-1,4-polyisoprene) molecule, could be removed leading to completely soluble polymer samples. All samples investigated possess a very broad (10 to 50,000 kg/mol) and distinct bimodal molar mass distribution. With increasing age the peak area in the low molar mass region decreases favoring the peak area in the high molar mass region. By plotting the branching index as a function of the both, the molar mass and the age of the trees.

Husbands' involvement in abortion in Vietnam.

This study analyzes the involvement of men in abortion in Vietnam, where induced abortion is legal and abortion rates are among the highest in the world. Twenty men were interviewed in 1996 about the role they played in their wives' abortions and about their feelings and ethical views concerning the procedure. The results showed that both husbands and wives considered the husband to be the main decisionmaker regarding family size, which included the decision to have an abortion, but that, in fact, some women had undergone an abortion without consulting their husbands in advance. Parents and in-laws were usually not consulted; the couples thought they might object to the decision on moral grounds. Respondents' ethical perspectives on abortion are discussed. When faced with an unwanted pregnancy, the husbands adopted an ethics of care and responsibility toward family and children, although some felt that abortion was immoral. The study highlights the importance of understanding husbands' perspectives on their responsibilities and rights in reproductive decisionmaking and their ethical and other concerns related to abortion.

PIP: This study explored men's attitudes and ethical views about abortion and their decision-making role in their wives' abortion in Viet Nam. Data were obtained from a 1996 survey conducted in the province of Quang Ninh and the towns of Uong Bi and La Hong. The total fertility rate in the study area was 2.3 children/woman. The total induced abortion rate was 2.5/woman, which is the highest in Viet Nam. The sample included 20 women drawn from a random sample of 300 women from 2 public abortion clinics. Findings indicate that the mean age of the 20 husbands was 37 years. Most came from large families with 6 children. No one was illiterate. The mean age at marriage was 26 years. The mean interval to first birth was 2 years. All had at least 1 child. The 20 women averaged 2.4 abortions/woman: 2.7 in La Hong and 1.9 in Uong Bi. Three case histories--an old man's, a middle-aged man's, and a young man's--are reported. The old man, who lived through the war years, had 2 sons and a daughter. His wife, after the last birth, had 1 miscarriage and 3 abortions. She removed the IUD due to side effects. The old man desired no more children. The middle-aged man viewed too many children as self-defeating. The young man thought life was too hard to support a large family. Reasons for abortion were mainly economic ones, protection of women's health, and adherence to the two-child policy. About 50% made the abortion decision together. Ethical views ranged from disapproval and deep moral concern to a neutral modern view. The concern for living children and family welfare took precedence.

Brain tumours in Ho Chi Minh City.

A series of 65 intracranial tumours operated on, and followed by, the same surgical team during 7 years is presented as a retrospective analysis (1987-1994). Among these patients, only 38 had a diagnosis based upon computed tomography (CT) scan because it was not until 1991 that the first CT scanner was set up in Ho Chi Minh City. Many patients were drowsy or comatose prior to operation due to lack of specialists' intervention or tardy diagnosis and evacuation from remote provincial hospitals. All operations were satisfactory despite the lack of many essential instruments. The histological diagnosis followed the classification proposed by Zulch KJ.(1) Intratumoural calcification has in no case been seen on X-rays or on histological specimens. Operative mortality rate was nil. Although not all the patients with malignant tumours could be followed up, the data available concerning their survival time and the quality of life seems similar to that observed in other reports.

Useful hints for the study of the history of orthopaedics.

Although there is considerable interest among orthopaedic surgeons in the history of their specialty, many fail to pursue their interest because of an unfamiliarity with the tools and methods by which historical information can be assembled. The purpose of this article is to point out the resources for historical research available to most physicians and to give some suggestions for their use.