Inactivated influenza vaccine formulated with single-stranded RNA-based adjuvant confers mucosal immunity and cross-protection against influenza virus infection

Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4⁺ and CD8⁺ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity.     

High-Frequency Irreversible Electroporation Using 5,000-V Waveforms to Create Reproducible 2- and 4-cm Ablation Zones—A Laboratory Investigation Using Mechanically Perfused Liver

PurposeTo investigate if high-frequency irreversible electroporation (H-FIRE) treatments can be delivered at higher voltages and with greater energy delivery rates than currently implemented in clinical irreversible electroporation protocols.Materials and MethodsTreatments using 3,000 V and 5,000 V were administered to mechanically perfused ex vivo porcine liver via a single applicator and grounding pad (A+GP) as well as a 4-applicator array (4AA). Integrated energized times (IET) 0.01–0.08 seconds and energy delivery rates 25–300 μs/s were investigated. Organs were preserved at 4°C for 10–15 hours before sectioning and gross analysis using a metabolic stain to identify the size and shape of ablation zones.ResultsA+GP ablations measured between 1.6 cm and 2.2 cm, which did not increase when IET was increased from 0.02 seconds to 0.08 seconds (P > .055; range, 1.9–2.1 cm). Changes in tissue color and texture consistent with thermal damage were observed for treatments with energy delivery rates 50–300 μs/s, but not for treatments delivered at 25 μs/s. Use of the 4AA with a 3-cm applicator spacing resulted in ablations measuring 4.4–4.9 cm with energy delivery times of 7–80 minutes.ConclusionsH-FIRE treatments can rapidly and reproducibly create 2-cm ablations using an A+GP configuration. Treatments without thermal injury were produced at the expense of extended treatment times. More rapid treatments resulted in ablations with varying degrees of thermal injury within the H-FIRE ablation zone. Production of 4-cm ablations is possible using a 4AA.     

Economic Evaluation of Factorial Trials: Cost-Utility Analysis of the Atorvastatin in Factorial With Omega EE90 Risk Reduction in Diabetes 2 × 2 × 2 Factorial Trial of Atorvastatin,Omega-3 Fish Oil,and Action Planning

ObjectivesWe applied principles for conducting economic evaluations of factorial trials to a trial-based economic evaluation of a cluster-randomized 2 × 2 × 2 factorial trial. We assessed the cost-effectiveness of atorvastatin, omega-3 fish oil, and an action-planning leaflet, alone and in combination, from a UK National Health Service perspective.MethodsThe Atorvastatin in Factorial With Omega EE90 Risk Reduction in Diabetes (AFORRD) Trial randomized 800 patients with type 2 diabetes to atorvastatin, omega-3, or their respective placebos and randomized general practices to receive a leaflet-based action-planning intervention designed to improve compliance or standard care. The trial was conducted at 59 UK general practices. Sixteen-week outcomes for each trial participant were extrapolated for 70 years using the United Kingdom Prospective Diabetes Study Outcomes Model v2.01. We analyzed the trial as a 2 × 2 factorial trial (ignoring interactions between action-planning leaflet and medication), as a 2 × 2 × 2 factorial trial (considering all interactions), and ignoring all interactions.ResultsWe observed several qualitative interactions for costs and quality-adjusted life-years (QALYs) that changed treatment rankings. However, different approaches to analyzing the factorial design did not change the conclusions. There was a ≥99% chance that atorvastatin is cost-effective and omega-3 is not, at a £20 000/QALY threshold.ConclusionsAtorvastatin monotherapy was the most cost-effective combination of the 3 trial interventions at a £20 000/QALY threshold. Omega-3 fish oil was not cost-effective, while there was insufficient evidence to draw firm conclusions about action planning. Recently-developed methods for analyzing factorial trials and combining parameter and sampling uncertainty were extended to estimate cost-effectiveness acceptability curves within a 2x2x2 factorial design with model-based extrapolation.     

绝经后女性2型糖尿病伴骨质疏松患者骨密度与骨代谢指标的相关性分析

目的分析研究绝经后女性2型糖尿病伴骨质疏松症患者骨密度与骨代谢指标的相关性。方法选取2013年10月至2017年05月于重庆医科大学附属第一医院内分泌内科住院的绝经后女性2型糖尿病患者385名。搜集其基本资料、骨代谢指标及骨密度等。根据T值将这些患者分为骨质疏松组(233例)、骨量减少组(101例)和骨量正常组(51例),比较三组间骨代谢指标的变化,并对骨密度(bone mineral density,BMD)与各项骨代谢指标进行相关性分析。结果 1型前胶原氨基末端前肽(Type I procollagen N-terminal propeptide,P1NP)、骨钙素(bone Gla protein,BGP)在骨质疏松组显著高于骨量减少组、骨量正常组(P0.05);随着骨密度的降低,1型胶原羧基端肽β特殊序列(β-Carboxyl terminal peptide,β-CTX)逐渐升高,骨质疏松组、骨量减少组与骨量正常组相比较差异有统计学意义(P0.05);Spearman等级相关分析示P1NP、BGP、β-CTX与骨密度呈负相关,25(OH)D_3与骨密度呈现正相关。结论绝经后女性2型糖尿病伴骨质疏松症患者骨密度与骨代谢指标有一定的相关性,有助于预测骨折风险并及时抗骨质疏松治疗。     

谷氨酸对腺苷A2A受体调节一氧化氮合酶活力的影响

目的探讨谷氨酸是否能够影响腺苷A2A受体对一氧化氮合酶（NOS）活力的调节。方法用1000ng／ml脂多糖（LPS）刺激小胶质细胞，分别加入100nmol／L A2A受体激动剂CGS21680以及不同浓度的谷氨酸（0，1，0，25，0，5mmol／L）干预，观察NOS活力变化。结果LPS诱导NOS活力增高，激活A2A受体可以产生抑制作用；0，25及0．5mmoL／L谷氨酸和A2A受体激动剂同时存在时，NOS活力进一步增高。结论高浓度谷氨酸可逆转腺苷A2A受体激动剂抑制升高NOS活力的作用。     

Faut-il être adventiste du 7 Jour pour être en bonne santé ?

Many health-related research studies among Seventh-day Adventists (SDA) were published since 1958. Californian and Norwegian studies have shown that SDA have lower coronary mortality rates than the general population. This finding is usually attributed to the lifestyle advocated by the Seventh-day Adventist church with greater physical activity, lower median BMI, abstention from use of alcohol and tobacco, food habits characterized by a large intake of fruits, vegetables, cereal fiber, unsaturated fatty acids and a low consumption of saturated fats. The results about cancer incidence were discussed. Californian studies have shown significantly decreased relative risk in SDA than in the general population. Japanese studies have also reported lower risk of cancers in men with lifestyles similar to those of SDA. By contrast the Norwegian study of SDA has shown that the risk of cancer seems to be similar to that of the general population. Some studies reported a greater prevalence of type 2 diabetes in the non vegetarian SDA than the vegetarian. Compared with vegetarian, non vegetarian SDA reported more medication use, more chronic diseases, more hospitalizations and surgeries. Lifestyle choices of SDA as above described could prevent a great many coronary artery disease and type 2 diabetes. This lifestyle is now emphasized by French PNNS.     

Improvements in healthcare and cost benefits associated with botulinum toxin treatment of spasticity and muscle overactivity

Spasticity is a widespread, disabling form of muscle overactivity affecting patients with central nervous system damage resulting in upper motor neurone syndrome. There is a range of effective therapies for the treatment of spasticity (e.g. physical, anaesthetic, chemodenervation and neurolytic injections, systemic medication and surgery), but all therapies must be based on an individualized, multidisciplinary programme targeted to achieve patient goals. Appropriate therapy should be based on the extent and severity of spasticity, but spasticity and its consequences, regardless of presentation or cause, are commonly treated with systemic agents. This may be ill-advised as systemic treatment is associated with many undesirable effects. In particular, elderly patients with post-stroke spasticity are at risk from the central adverse effects of systemic medication (e.g. sedation and gait disturbance), which make them more susceptible to falling, with an associated increased risk of fracture. The rising costs of fracture care and its sequelae are fast becoming an international problem contributing to high healthcare expenditure. Botulinum toxin type-A (BoNT-A) treatment is highly effective for some of the more common forms of spasticity and muscle overactivity, and has a favourable profile when compared with systemic agents and other focal treatments. Therefore, the clinical benefits of BoNT-A treatment outweigh the apparent high costs of this intervention, showing it to be a cost-effective treatment.