A Multi-Center Randomised Controlled Trial of Gatifloxacin versus Azithromycin for the Treatment of Uncomplicated Typhoid Fever in Children and Adults in Vietnam

BACKGROUND: Drug resistant typhoid fever is a major clinical problem globally. Many of the first line antibiotics, including the older generation fluoroquinolones, ciprofloxacin and ofloxacin, are failing. OBJECTIVES: We performed a randomised controlled trial to compare the efficacy and safety of gatifloxacin (10 mg/kg/day) versus azithromycin (20 mg/kg/day) as a once daily oral dose for 7 days for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. METHODS: An open-label multi-centre randomised trial with pre-specified per protocol analysis and intention to treat analysis was conducted. The primary outcome was fever clearance time, the secondary outcome was overall treatment failure (clinical or microbiological failure, development of typhoid fever-related complications, relapse or faecal carriage of S. typhi). PRINCIPAL FINDINGS: We enrolled 358 children and adults with suspected typhoid fever. There was no death in the study. 287 patients had blood culture confirmed typhoid fever, 145 patients received gatifloxacin and 142 patients received azithromycin. The median FCT was 106 hours in both treatment arms (95% Confidence Interval [CI]; 94-118 hours for gatifloxacin versus 88-112 hours for azithromycin), (logrank test p = 0.984, HR [95% CI] = 1.0 [0.80-1.26]). Overall treatment failure occurred in 13/145 (9%) patients in the gatifloxacin group and 13/140 (9.3%) patients in the azithromycin group, (logrank test p = 0.854, HR [95% CI] = 0.93 [0.43-2.0]). 96% (254/263) of the Salmonella enterica serovar Typhi isolates were resistant to nalidixic acid and 58% (153/263) were multidrug resistant. CONCLUSIONS: Both antibiotics showed an excellent efficacy and safety profile. Both gatifloxacin and azithromycin can be recommended for the treatment of typhoid fever particularly in regions with high rates of multidrug and nalidixic acid resistance. The cost of a 7-day treatment course of gatifloxacin is approximately one third of the cost of azithromycin in Vietnam. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN67946944

A modified Sequential Organ Failure Assessment score for dengue: development, evaluation and proposal for use in clinical trials

Background Dengue is a neglected tropical disease, for which no therapeutic agents have shown clinical efficacy to date. Clinical trials have used strikingly variable clinical endpoints, which hampers reproducibility and comparability of findings. We investigated a delta modified Sequential Organ Failure Assessment (delta mSOFA) score as a uniform composite clinical endpoint for use in clinical trials investigating therapeutics for moderate and severe dengue. Methods We developed a modified SOFA score for dengue, measured and evaluated its performance at baseline and 48 h after enrolment in a prospective observational cohort of 124 adults admitted to a tertiary referral hospital in Vietnam with dengue shock. The modified SOFA score included pulse pressure in the cardiovascular component. Binary logistic regression, cox proportional hazard and linear regression models were used to estimate association between mSOFA, delta mSOFA and clinical outcomes. Results The analysis included 124 adults with dengue shock. 29 (23.4%) patients required ICU admission for organ support or due to persistent haemodynamic instability: 9/124 (7.3%) required mechanical ventilation, 8/124 (6.5%) required vasopressors, 6/124 (4.8%) required haemofiltration and 5/124 (4.0%) patients died. In univariate analyses, higher baseline and delta (48 h) mSOFA score for dengue were associated with admission to ICU, requirement for organ support and mortality, duration of ICU and hospital admission and IV fluid use. Conclusions The baseline and delta mSOFA scores for dengue performed well to discriminate patients with dengue shock by clinical outcomes, including duration of ICU and hospital admission, requirement for organ support and death. We plan to use delta mSOFA as the primary endpoint in an upcoming host-directed therapeutic trial and investigate the performance of this score in other phenotypes of severe dengue in adults and children

Effect of Ignition Energy and Hydrogen Addition on Laminar Flame Speed, Ignition Delay Time, and Flame Rising Time of Lean Methane/Air Mixtures

A series of experiments were performed to investigate the effect of ignition energy (Eig) and hydrogen addition on the laminar burning velocity (Su0), ignition delay time (tdelay), and flame rising time (trising) of lean methane−air mixtures. The mixtures at three different equivalence ratios (ϕ) of 0.6, 0.7, and 0.8 with varying hydrogen volume fractions from 0 to 50% were centrally ignited in a constant volume combustion chamber by a pair of pin-to-pin electrodes at a spark gap of 2.0 mm. In situ ignition energy (Eig ∼2.4 mJ ÷ 58 mJ) was calculated by integration of the product of current and voltage between positive and negative electrodes. The result revealed that the Su0 value increases non-linearly with increasing hydrogen fraction at three equivalence ratios of 0.6, 0.7, and 0.8, by which the increasing slope of Su0 changes from gradual to drastic when the hydrogen fraction is greater than 20%. tdelay and trising decrease quickly with increasing hydrogen fraction; however, trising drops faster than tdelay at ϕ = 0.6 and 0.7, and the reverse is true at ϕ = 0.8. Furthermore, tdelay transition is observed when Eig > Eig,critical, by which tdelay drastically drops in the pre-transition and gradually decreases in the post-transition. These results may be relevant to spark ignition engines operated under lean-burn conditions

ẢNH HƯỞNG CỦA NHIỆT ĐỘ LÊN TÍNH CHẤT QUANG CỦA HẠT NANO VÀNG BỌC BẰNG PROTEIN

In this paper, we describe the dependence of the optical properties of proteins-bovine-serum- albumin (BSA)-coated gold nanoparticles with temperature using the soliton phase transition theory. Gold nanoparticles with a radius r coated by a protein with a layer thickness d make the effective radius R of the gold nanoparticles increase. When the temperature does not change, the particle radius increases slightly, and the absorption wavelength linearly depends on the particle radius. When the environment temperature around of sphere-complex system changes, the effective radius of the particle R depends on the temperature because the thickness of the protein layer varies. At the temperature of protein denaturation, the effective radius of the particle rapidly increases due to sudden stretching of the BSA protein, leading to redshift in the spectrum of the spherical-complex system. With this model, we have initially identified the form of the function expressing the absorption wavelength – temperature relationship of BSA protein-coated gold nanoparticles (the tan function) and it has a good agreement with the experimental data.Trong bài báo này, chúng tôi mô tả sự phụ thuộc tính chất quang của hạt nano vàng bọc bằng bằng protein bovine serum albumin (BSA) theo nhiệt độ, sử dụng lý thuyết chuyển pha soliton. Hạt nano vàng có bán kính r khi bọc bằng lớp protein có bề dày là d làm cho bán kính hiệu dụng R của hạt nano vàng tăng lên. Khi chưa tính đến sự thay đổi nhiệt độ của môi trường thì bán kính hạt tăng lên không đáng kể. Bước sóng hấp thụ phụ thuộc tuyến tính vào bán kính hạt. Khi nhiệt độ môi trường bao quanh hệ phức hạt thay đổi thì bán kính hiệu dụng của hạt R phụ thuộc vào nhiệt độ, do bề dày của lớp protein thay đổi theo nhiệt độ. Tại nhiệt độ biến tính TC của protein, bán kính hiệu dụng của hạt tăng nhanh do protein BSA bất ngờ duỗi ra, dẫn đến sự dịch phổ đỏ của hệ phức hạt cầu. Theo mô hình này chúng tôi đã bước đầu xác định được dạng hàm phụ thuộc của bước sóng hấp thụ của hạt nano vàng bọc bằng protein BSA vào nhiệt độ là hàm tan và khi so sánh với thực nghiệm thấy có sự phù hợp khá tốt

Edge Termination Design Improvements for 10 kV 4H-SiC Bipolar Diodes

International audience10 kV class 4H-SiC bipolar diodes have been fabricated. Two different edge terminations (Mesa/JTE or MESA/JTE with JTE rings) with two different junction bend radius have been designed and tested. Measurement results show that the inclusion of JTE rings improve the edge termination efficiency. The measurements indicate also a better reverse performance of diodes with larger bend radius

Oro-Dental Health and Primary Nephrotic Syndrome among Vietnamese Children

Primary nephrotic syndrome (PNS) is common in children, affecting the soft and hard tissues of the oral cavity. This study aimed to investigate the percentage of dental caries, gingivitis, hypertrophic gingivitis, and developmental defects of enamel (DDE) in children with PNS. The association of PNS with these diseases and oral care behavior was also assessed. A total of 407 children with PNS and 407 age- and gender-matched controls were recruited. PNS was diagnosed based on blood and urinary tests. The Simplified Oral Hygiene Index (OHI-S), the Gingival Index (GI), the Gingival Overgrowth Index (GOI), the Decayed, Missing, and Filled Teeth Index (dmft/DMFT), and DDE were collected. The PNS patients showed significantly higher scores of OHI-S, GI, and dmft, and higher proportions of dental caries and DDE than those of the controls (p < 0.001). It is necessary to establish a periodic dental protocol for PNS patients to improve their oral health status

Promising clinical and immunological efficacy of Bacillus clausii spore probiotics for supportive treatment of persistent diarrhea in children

Abstract Persistent diarrhea is a severe gastroenteric disease with relatively high risk of pediatric mortality in developing countries. We conducted a randomized, double-blind, controlled clinical trial to evaluate the efficacy of liquid-form Bacillus clausii spore probiotics (LiveSpo CLAUSY; 2 billion CFU/5 mL ampoule) at high dosages of 4–6 ampoules a day in supporting treatment of children with persistent diarrhea. Our findings showed that B. clausii spores significantly improved treatment outcomes, resulting in a 2-day shorter recovery period (p < 0.05) and a 1.5–1.6 folds greater efficacy in reducing diarrhea symptoms, such as high frequency of bowel movement of ≥ 3 stools a day, presence of fecal mucus, and diapered infant stool scale types 4-5B. LiveSpo CLAUSY supportive treatment achieved 3 days (p < 0.0001) faster recovery from diarrhea disease, with 1.6-fold improved treatment efficacy. At day 5 of treatment, a significant decrease in blood levels of pro-inflammatory cytokines TNF-α, IL-17, and IL-23 by 3.24% (p = 0.0409), 29.76% (p = 0.0001), and 10.87% (p = 0.0036), respectively, was observed in the Clausy group. Simultaneously, there was a significant 37.97% decrease (p = 0.0326) in the excreted IgA in stool at day 5 in the Clausy group. Overall, the clinical study demonstrates the efficacy of B. clausii spores (LiveSpo CLAUSY) as an effective symptomatic treatment and immunomodulatory agent for persistent diarrhea in children. Trial registration: NCT05812820

Involvement of Secondary Metabolites in Response to Drought Stress of Rice (Oryza sativa L.)

In this study, responses of rice under drought stress correlating with changes in chemical compositions were examined. Among 20 studied rice cultivars, Q8 was the most tolerant, whereas Q2 was the most susceptible to drought. Total phenols, total flavonoids, and antioxidant activities, and their accumulation in water deficit conditions were proportional to drought resistance levels of rice. In detail, total phenols and total flavonoids in Q8 (65.3 mg gallic acid equivalent (GAE) and 37.8 mg rutin equivalent (RE) were significantly higher than Q2 (33.9 mg GAE/g and 27.4 mg RE/g, respectively) in both control and drought stress groups. Similarly, the antioxidant activities including DPPH radical scavenging, β-carotene bleaching, and lipid peroxidation inhibition in Q8 were also higher than in Q2, and markedly increased in drought stress. In general, contents of individual phenolic acids in Q8 were higher than Q2, and they were significantly increased in drought stress to much greater extents than in Q2. However, p-hydroxybenzoic acid was found uniquely in Q8 cultivars. In addition, only vanillic acid was found in water deficit stress in both drought resistant and susceptible rice, suggesting that this phenolic acid, together with p-hydroxybenzoic acid, may play a key role in drought-tolerance mechanisms of rice. The use of vanillic acid and p-hyroxybenzoic acid, and their derivatives, may be useful to protect rice production against water shortage stress