茶树精油对铜绿假单胞杆菌生物膜的抑制作用

目的 观察茶树精油对铜绿假单胞杆菌生物膜(BF)的抑制作用.方法 采用二倍稀释法测定茶树精油对铜绿假单胞杆菌的最小抑菌浓度(MIC),以一次性输液管和微孔滤膜作为生物膜吸附载体,用改良后的Brown平板连续培养法制备铜绿假单胞杆菌生物膜体外模型,采用光学高倍显微镜连续观察生物膜的形成,采用扫描电子显微镜进行生物膜结构观察和鉴定,以琼脂平板菌落计数法测定茶树精油对受试菌生物膜的抑制效果.结果 茶树精油对铜绿假单胞杆菌的MIC(孟乙烯4-ol浓度含量)为9.6μg/ml; 0.5倍MIC (4.8 μg/ml)、1倍MIC(9.6 μg/ml)虽能使成熟铜绿假单胞杆菌生物膜菌落数呈梯度性减少,但不能完全清除生物膜细菌,而2倍MIC(19.2 μg/ml)对细菌生物膜作用20 h后可完全清除生物膜细菌,3倍MIC(28.8μg/ml)则可在4h内完全清除生物膜.结论 茶树精油对铜绿假单胞菌生物膜有清除效应,可抑制生物膜形成,但需进一步研究验证.     

Safety,immunogenicity, and efficacy of NDV-3A against Staphylococcus aureus colonization: A phase 2 vaccine trial among US Army Infantry trainees

BackgroundMilitary trainees are at increased risk for Staphylococcus aureus colonization and infection. Disease prevention strategies are needed, but a S. aureus vaccine does not currently exist.MethodsWe enrolled US Army Infantry trainees (Fort Benning, GA) in a phase 2, randomized, double-blind, placebo-controlled trial of NDV-3A, a vaccine containing a recombinant adhesin/invasion protein of Candida albicans that has structural similarity to the S. aureus protein clumping factor A. Study participants received one intramuscular dose of NDV-3A or placebo (adjuvant alone) within 72 h of arrival on base. Longitudinal nasal and oral (throat) swabs were collected throughout the 14-week Infantry training cycle. Safety, immunogenicity, and efficacy of NDV-3A against S. aureus nasal / oral acquisition were the endpoints.ResultsThe NDV-3A candidate had minimal reactogenicity and elicited robust antigen-specific B- and T-cell responses. During the 56-day post-vaccination period, there was no difference in the incidence of S. aureus nasal acquisition between those who were randomized to receive NDV-3A vs. placebo (25.6% vs. 29.1%; vaccine efficacy [VE]: 12.1%; p = 0.31). In time-to-event analysis, there was no difference between study groups with respect to the S. aureus colonization-free interval (VE: 13%; p = 0.29). Similarly, the efficacy of NDV-3A against S. aureus oral acquisition was poor (VE: 2.4%; p = 0.52).ConclusionsA single dose of NDV-3A did not prevent nasal nor oral acquisition of S. aureus in a population of military trainees at high risk for colonization.     

Immunogenicity and safety of double versus standard dose of the seasonal influenza vaccine in solid-organ transplant recipients: A randomized controlled trial

BackgroundThe use of vaccines with higher doses of antigen is an attractive strategy to improve the immunogenicity of influenza vaccination in transplant recipients. However, the effect of vaccination with a double-dose (DD) containing 30 µg of antigen in this population remains unknown.MethodsWe performed a randomized controlled trial to compare the immunogenicity and safety of DD (30 µg) vs. standard dose (SD, 15 µg) of a trivalent inactivated influenza vaccine in kidney and liver transplant recipients. Immunogenicity was assessed by hemagglutination-inhibition assay. Vaccine response was defined as seroconversion to at least one viral strain 2 weeks after vaccination and seroprotection as a titer ≥40.ResultsSixty-three kidney and 16 liver transplant recipients were enrolled. Forty patients received the DD and 39 the SD vaccine. Overall, 40% of patients in the DD compared to 26% in the SD group (P = 0.174) responded to vaccine. In the DD arm, more patients were seroprotected to all viral strains after vaccination (88% vs 69%, P = 0.048). Post vaccination geometric mean titers of antibodies were 131.9 vs. 89.7 (P = 0.187) for H1N1, 185.4 vs. 138.7 (P = 0.182) for H3N2, and 96.6 vs. 68.8 (P = 0.081) for influenza B with the DD vs. SD. In both groups, most of the adverse events were mild and no vaccine-related severe adverse events were observed.ConclusionDouble-dose influenza vaccine is safe and may increase antibody response in transplant recipients. In this population, DD vaccination could be an alternative when high-dose vaccine is not available. NCT02746783.     

A prospective study of the reliability and convergent validity of three physical activity measures in a field research trial

This investigation sought to determine the test-retest reliability and convergent validity of three commonly used physical activity measures. The Stanford Physical Activity Recall, the Caltrac Activity Monitor, and a daily physical activity log were administered to 45 subjects over a 3-week period. The results indicated high levels of test-retest reliability for the Stanford and the daily log; low test-retest reliability was obtained for the Caltrac. Convergent validity was also high between the Stanford and daily log but was low for both of these measures with the Caltrac: These results suggest that the Stanford Physical Activity Recall may be the self-report measure of choice for large studies due to its high reliability and convergent validity with a more time-consuming daily log, as well as its cost- and time-efficiency. Based on the results, it is recommended that the Caltrac activity sensors not be used for field studies of physical activity until the logistical problems of their use in clinical trials are solved.     

Rationale and design of a randomized clinical trial on prevention of stroke in isolated systolic hypertension

Isolated systolic hypertension (ISH)-ix. high systolic pressure with nonhypertensive (< 90 mmHg) diastolic pressure—is a recognized risk factor for cardiovascular disease among individuals in the age group 60 years and above. This observation suggests that antihypertensive treatment might be beneficial. Results of the Systolic Hypertension in the Elderly Program Pilot Study (SHEP-PS) indicated the feasibility of a full-scale clinical trial on the efficacy of drug treatment of ISH.

The Systolic Hypertension in the Elderly Program (SHEP) is a randomized, double-blind, placebo-controlled clinical trial with the primary objective of assessing the effect of drug treatment of ISH—systolic pressure 160–219 mmHg and diastolic pressure <90—on occurrence of fatal and nonfatal stroke. This multicenter clinical trial has a sample size of 4736 participants, with high statistical power to detect a reduction of 32% or more in the study's primary end point during the 4–6 year period of treatment and follow-up. Low dosage chlorthalidone is the main study drug. Further features of the design of SHEP and the trial's organization are described.     

Oral misoprostol versus vaginal gemeprost for cervical dilatation prior to vacuum aspiration in women in the sixth to twelfth week of gestation

The effectiveness of oral misoprostol versus vaginal gemeprost for cervical dilatation prior to vacuum aspiration was compared in women in the 6th to 12th week of pregnancy. Sixty-four nulliparous women requesting termination of pregnancy between 6th to 12th weeks of gestation were randomized to receive either 400 μg misoprostol orally or 1 mg vaginal gemeprost at 12 hr or 3 hr prior to vacuum aspiration, respectively. The cervical dilatation at vacuum aspiration, the ease of the subsequent surgical procedure, and the incidence of complications and side effects were compared between these two methods of cervical priming. The median cervical dilatation at vacuum aspiration in the misoprostol group was significantly greater than that in the gemeprost group (8.0 mm versus 7.0 mm, p<0.02). Preoperative side effects were significantly less frequent in the misoprostol group (p<0.01). The ease of dilatation assessed subjectively by the operating surgeons was also improved significantly in the misoprostol group (p<0.01). However, the duration of operation and blood loss were similar in both groups. Since misoprostol is also much cheaper and more convenient to use, we conclude that oral misoprostol is better than vaginal gemeprost for cervical dilatation prior to vacuum aspiration in first trimester pregnancy.     

Comparison of a single,high-dose vaccination regimen to the standard regimen for the investigational Japanese encephalitis vaccine,IC51: A randomized,observer-blind,controlled Phase 3 study

The standard administration of the investigational Japanese encephalitis vaccine IC51 is 2 doses of 6 μg with a 28-day interval. This study investigated the immunogenicity of a single-immunization, high-dose regimen (1 × 12 μg) compared to the 2-injection, standard regimen to determine the immune response that one, high-dose injection can confer. The single, high-dose regimen resulted in about 60% seroconversion rate (SCR) at 10 days after administration, but it did not reach the almost 100% SCR achieved by the 2-dose standard administration at Day 35. The standard regimen conferred essentially 100% seroconversion already 7 days after the second immunization.     

A randomized, controlled, single-blind trial of teaching provided by a computer-based multimedia package versus lecture

BACKGROUND: Computer-based teaching may allow effective teaching of important psychiatric knowledge and skills. AIMS: To investigate the effectiveness and acceptability of computer-based teaching. METHOD: A single-blind, randomized, controlled study of 166 undergraduate medical students at the University of Leeds, involving an educational intervention of either a structured lecture or a computer-based teaching package (both of equal duration). RESULTS: There was no difference in knowledge between the groups at baseline or immediately after teaching. Both groups made significant gains in knowledge after teaching. Students who attended the lecture rated their subjective knowledge and skills at a statistically significantly higher level than students who had used the computers. Students who had used the computer package scored higher on an objective measure of assessment skills. Students did not perceive the computer package to be as useful as the traditional lecture format, despite finding it easy to use and recommending its use to other students. CONCLUSIONS: Medical students rate themselves subjectively as learning less from computer-based as compared with lecture-based teaching. Objective measures suggest equivalence in knowledge acquisition and significantly greater skills acquisition for computer-based teaching.     

Immunogenicity and safety of a two-dose regimen with hepatitis E virus vaccine in healthy adults in rural Bangladesh: A randomized,double-blind,controlled, phase 2/pilot trial

BackgroundHepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide and it contributes to considerable maternal and neonatal mortality and morbidity in many low-income countries like Bangladesh. A three-dose regimen of a vaccine against HEV (HEV 239) has shown promising results in China. The effects and safety of this vaccine in other populations and with different dosing regimens remains uncertain.ObjectivesInvestigate the immune response and safety of a two-dose regimen with the HEV 239 vaccine among healthy adults. Examine the feasibility of conducting a larger HEV 239 vaccine trial in rural Bangladesh.MethodsOne-hundred healthy men and non-pregnant women 16–39 years old were randomized in a 1:1 ratio to receive two doses of either the study (HEV) or control (Hepatitis B virus, HBV) vaccine (at 0, 1 month). Blood samples were collected at day 0, day 60 and 2 years after vaccination. The primary endpoints were the proportion and severity of adverse events up to 2 months after dose one and the longitudinal shift in anti-HEV IgG levels from day 0 to day 60 and 2 years after vaccination.ResultsAdverse events to HEV 239 were comparable to the control vaccine, mild in severity and resolved within one to nine days. All participants in the study group seroconverted and achieved high levels of HEV IgG antibodies that remained positive for two years in all but one. A T-cell response was detected one month after HEV 239 vaccination.ConclusionOur results show that two doses of the HEV 239 vaccine produces broad and likely functional immune responses against HEV that remain for at least two years. The safety profile was acceptable and a phase four study of HEV 239 in rural Bangladesh is feasible.ClinicalTrials.gov Identifier: NCT02759991.     

A randomized clinical trial of a booster dose with low versus standard dose of AZD1222 in adult after 2 doses of inactivated vaccines

BackgroundImmunogenicity of inactivated SARS-CoV-2 vaccine has waning antibody over time. With the emergence of the SARS-CoV-2 delta variant, which requires higher neutralizing antibody to prevent infection, a booster dose is needed.ObjectiveTo evaluate immunogenicity and reactogenicity of standard- versus low-dose ChAdOx1 nCoV-19 vaccine booster after CoronaVac in healthy adults.MethodsA double-blinded, randomized, controlled trial of adult, aged 18–59 years, with completion of 2-dose CoronaVac at 21–28 days apart for more than 2 months was conducted. Participants were randomized to receive AZD1222 (Oxford/AstraZeneca) intramuscularly; standard dose (SD, 5x10¹⁰ viral particles) or low dose (LD, 2.5x10¹⁰ viral particles). Surrogate virus neutralization test (sVNT) against wild type and delta variant, and anti-spike-receptor-binding-domain IgG (anti-S-RBD IgG) were compared as geometric mean ratio (GMR) at day 14 and 90 between LD and SD arms.ResultsFrom July-August 2021, 422 adults with median age of 44 (IQR 36–51) years were enrolled. The median interval from CoronaVac to AZD1222 booster was 77 (IQR 64–95) days. At baseline, geometric means (GMs) of sVNT against delta variant and anti-S-RBD IgG were 18.1%inhibition (95% CI 16.4–20.0) and 111.5 (105.1–118.3) BAU/ml. GMs of sVNT against delta variant and anti-S-RBD IgG in SD were 95.6%inhibition (95% CI 94.3–97.0) and 1975.1 (1841.7–2118.2) BAU/ml at day 14, and 89.4%inhibition (86.4–92.4) and 938.6 (859.9–1024.4) BAU/ml at day 90, respectively. GMRs of sVNT against delta variant and anti-S-RBD IgG in LD compared to SD were 1.00 (95% CI 0.98–1.02) and 0.84 (0.76–0.93) at day 14, and 0.98 (0.94–1.03) and 0.89 (0.79–1.00) at day 90, respectively. LD recipients had significantly lower rate of fever (6.8% vs 25.0%) and myalgia (51.9% vs 70.7%) compared to SD.ConclusionHalf-dose AZD1222 booster after 2-dose inactivated SARS-CoV-2 vaccination had non-inferior immunogenicity, yet lower systemic reactogenicity. Fractional low-dose AZD1222 booster should be considered especially in resource-constrained settings.     

Termination of early pregnancy by two regimens of mifepristone with misoprostol and mifepristone with PG05—a multicentre randomized clinical trial in China

A multicentre randomized open clinical trial was conducted to compare the efficacy and side effects of two regimens of mifepristone with misoprostol, and mifepristone with PG05 for termination of early pregnancy (amenorrhoea < = 49 days). Six-hundred women in early pregnancy, who requested medical abortion were randomly allocated into 3 groups. In group 1 (n = 301), an initial dose of mifepristone 50 mg was given, followed by 25 mg every 12 hours up to a total dose of 150 mg mifepristone, plus a single oral dose of misoprostol 600 μg in the morning of the third day. In group 2 (n = 150), the same regimen of mifepristone was given, but dl-15-methyl PGF₂ (PG05) 1 mg vaginal suppository was inserted on the third day. In group 3 (n = 149), a single dose of mifepristone 200 mg was given and misoprostol 600 μg was used as in group 1. The complete abortion rate were 94.4%, 97.3%, and 94.6% for group 1, 2 and 3, respectively. 3.0, 2.0 and 2.7% of women had incomplete abortion, and 1.7, 0.7 and 2.0% of women in the 3 groups were treatment failures; in the remaining 1% in group 1 and 0.7% in group 3, treatment outcome could not be determined. There were no significant differences among the 3 groups. Lower abdominal pain was the main complaint which was reported by 82% of the subjects after PGs administration. The incidence of diarrhoea in PG05 group (38.7%) was significantly higher than that in the other two groups (21.6 and 20.1%) (P < 0.001), and so was vomiting. It was concluded that misoprostol, as an orally effective prostaglandin, in combination with mifepristone for induced abortion of early pregnancy was as effective as PG05 vaginal suppository. Besides, it has advantages of convenience of use, less side effects, easy storage and transfer, and low cost.     

A comparative evaluation of two investigational meningococcal ABCWY vaccine formulations: Results of a phase 2 randomized,controlled trial

BackgroundA meningococcal vaccine protective against all major disease-associated serogroups (A, B, C, W and Y) is an unmet public health need. In this phase 2 observer-blinded, randomized, controlled study, two investigational meningococcal ABCWY vaccine formulations were evaluated to assess their immunological noninferiority to a licensed quadrivalent meningococcal ACWY glycoconjugate vaccine (MenACWY-CRM) for serogroups ACWY and immunogenicity against serogroup B test strains, as well as for formulation selection based on a desirability index (DI). Each investigational MenABCWY formulation contained recombinant protein and outer membrane vesicle (OMV) components of a licensed serogroup B vaccine (4CMenB) combined with components of MenACWY-CRM.MethodsA total of 484 healthy 10–25 year-old participants were randomized to receive two doses, two months apart, of an investigational MenABCWY formulation that contained either a full or one-quarter dose of OMV, 4CMenB alone, or a Placebo followed by MenACWY-CRM. Immunogenicity against each of serogroups ACWY and four serogroup B test strains was assessed by serum bactericidal assay with human complement (hSBA). MenABCWY formulations were compared by a DI based on key immunogenicity and reactogenicity parameters.ResultsSeroresponse rates for serogroups ACWY were significantly higher after two doses of either MenABCWY formulation than after one dose of MenACWY-CRM: respectively, A: 90–92% vs. 73%; C: 93–95% vs. 63%; W: 80–84% vs. 65%; and Y: 90–92% vs. 75%. Prespecified noninferiority criteria were met. Both MenABCWY formulations induced substantial immune responses against serogroup B test strains, although 4CMenB responses were higher. Overall DIs for both MenABCWY formulations were similar. Reactogenicity profiles of the MenABCWY formulations were similar to each other and to that of 4CMenB. No vaccine-related serious adverse events were reported.ConclusionsBoth investigational MenABCWY formulations elicited robust immune responses against serogroups ACWY and serogroup B test strains, and had acceptable reactogenicity profiles, with no safety concerns identified.     

Effectiveness of a serious game on the self-concept of children with visual impairments: A randomized controlled trial

BackgroundYoung children with visual impairments (VIs) are at high risk for mental disorders, due to victimization and subsequent social withdrawal. Children with VIs have been shown to have a poorer self-concept and lower general psychosocial well-being compared with peers without VIs.ObjectiveThe objective of this study was to examine the effectiveness of a serious game to improve psychosocial outcomes in children with VIs.MethodsA randomized controlled trial was conducted to evaluate the effectiveness of the computer game See for children with VIs. The game was developed based on rational-emotive behavioral therapy principles, with the aim of addressing self-concept (academic, social, and general), psychosocial well-being (social inclusion, exclusion, and emotions), and coping strategies (approach, avoidance). Sixty-four children aged 6–8 years were randomized to the intervention group, who played the game, or a control group, who received care-as-usual (CAU).ResultsOur results showed that children with VIs who played the serious game scored significantly higher on academic self-concept and social inclusion compared with the control group. Furthermore, children rated the game positively, suggesting the desirability, validity, and feasibility of the intervention.ConclusionsThe results provide preliminary evidence that a serious game can enhance psychosocial outcomes in children with VIs. This approach might also promote positive educational outcomes, such as academic achievement, and reduce the stigma of therapy for children with VIs. Implications and future directions are discussed.     

A preliminary report of a randomized controlled phase 2 trial of the safety and immunogenicity of mRNA-1273 SARS-CoV-2 vaccine

BackgroundVaccines are urgently needed to prevent the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the safety and immunogenicity of vaccine candidate mRNA-1273, encoding the prefusion-stabilized spike protein of SARS-CoV-2.MethodsThis phase 2, randomized, observer-blind, placebo-controlled trial was conducted at 8 sites in the USA, in healthy adults aged ≥18 years with no known history or risk of SARS-CoV-2 infection, and had not previously received an investigational CoV vaccine or treatment. Participants were stratified into two age cohorts (≥18-<55 and ≥55) and were randomly assigned (1:1:1) to either 50 or 100 µg of mRNA-1273, or placebo administered as two intramuscular injections 28 days apart. The primary outcomes were safety, reactogenicity, and immunogenicity assessed by anti-SARS-CoV-2-spike binding antibody level (bAb). Secondary outcome was immunogenicity assessed by SARS-CoV-2 neutralizing antibody (nAb) response.ResultsBetween 29 May and 8 July 2020, 600 participants were randomized, 300 per age cohort. The most common solicited adverse reactions were pain at injection site, headache, and fatigue following each vaccination in both age cohorts. One serious adverse event deemed unrelated by the site investigator occurred 33 days post-vaccination one. mRNA-1273 induced bAb and nAb by 28 days post-vaccination one that were higher at the 100 µg dose relative to the 50 µg dose; this difference was less apparent post-vaccination two. Binding antibodies and nAb increased substantially by 14 days following the second vaccination (day 43) to levels exceeding those of convalescent sera and remained elevated through day 57.ConclusionsVaccination with mRNA-1273 resulted in significant immune responses to SARS-CoV-2 in participants 18 years and older, with an acceptable safety profile, confirming the safety and immunogenicity of 50 and 100 µg mRNA-1273 given as a 2 dose-regimen.ClinicalTrials.gov; NCT04405076.     

Arandomized multicentre trial of the Multiload 375 and TCu380A lUDs in parous women: three-year results

Two copper IUDs—the Multiload 375 and TCu380A—are being studied in a randomized multicentre study in parous women involving nineteen centres in nine countries. There have been 1,832 insertions of the Multiload 375 and 1,823 of the TCu380A. After three years of use, the Multiload 375 had a pregnancy rate that was significantly higher than the TCu380A (2.9 ± 0.4 vs. 1.6 ± 0.3 per 100 women). There were no differences at one, two and three years of use in the expulsion rates. It is concluded that the Multiload 375 shows no clinical advantages over the TCu380A and its extra cost should be an important consideration in the choice of the most appropriate IUD.