Reference antigen-free and antibody-free LTD-IDMS assay for influenza H7N9 vaccine in vitro potency determination

Influenza vaccines are the most effective intervention to prevent the substantial public health burden of seasonal and pandemic influenza. Hemagglutinin (HA), as the main antigen in inactivated influenza vaccines (IIVs), elicits functional neutralizing antibodies and largely determines IIV effectiveness. HA potency has been evaluated by single-radial immunodiffusion (SRID), the standard in vitro potency assay for IIVs, to predict vaccine immunogenicity with a correlation to protective efficacy. We previously reported that limited trypsin digestion (LTD) selectively degraded stressed HA, so that an otherwise conformationally insensitive biophysical quantification technique could specifically quantify trypsin-resistant, immunologically active HA. Here, we demonstrate that isotope dilution mass spectrometry (IDMS), a method capable of quantifying the absolute HA concentration without reference antigen use, can be further expanded by adding LTD followed with precipitation to selectively quantify the active HA. We test the LTD-IDMS assay on H7N9 vaccines stressed by low pH, raised temperature, or freeze/thaw cycles. This method, unlike SRID, has no requirement for strain-specific reference antigens or antibodies and can generate potency values that correlate with SRID. Thus, LTD-IDMS is a promising alternative in vitro potency assay for influenza vaccines to complement and potentially replace SRID in a pandemic when strain specific reagents may not be readily available.     

From Energy Efficiency Under Stress to Rapid Development and a Long Life in Natural Populations

Simplistically, high fitness depends upon high energy efficiency in the stressful habitats of organisms in the wild. Rapid development and high survival to adulthood should be followed by long-lived stress-resistant genotypes under this reductionist model. Empirical evidence is very limited because of the common use of benign laboratory environments, which remains a major difficulty in understanding relationships between life-history traits under more natural settings. Heterozygotes tend to show greater energy efficiency than do corresponding homozygotes especially in stressful environments, which leads the above connections among fitness traits. In particular rapid development and increased longevity should be correlated, and underwritten by the availability of metabolic energy. Empirical work is needed based upon severe stresses where a small environmental perturbation cases lethality; drought, heat and nutritional inadequacy are suitable candidate stresses. The importance of viewing fitness in energy terms is emphasized throughout. A byproduct is the potential to fuse functional and evolutionary biology under stressful environments.     

降雨对红火蚁蚁群行为的影响

目的研究红火蚁（Solenopsis invicta Buren）在雨前、雨中和雨后的行为习性以及雨季期间蚁巢消长情况,为防控红火蚁提供理论依据。方法采用野外实地观察的方法进行研究。结果红火蚁能够感知降雨的到来,在雨前采取加厚蚁丘表土层、加固蚁巢内部结构来防护蚁巢;雨中与雨后工蚁通过蚁巢出口孔向外搬运潮湿土粒、蒸发蚁巢内水分来修复蚁巢。大雨时红火蚁将未成年蚁集中搬运到地势较高的蚁丘表土层下,防止未成年蚁受到雨水的浸泡,而在短时暴雨时工蚁迅速聚集起来,用身体将蚁巢出口孔堵塞,阻止雨水灌入巢中。小雨和长时间大雨对工蚁觅食无明显的影响,而短时暴雨将严重抑制其觅食行为。此外,持续性强降雨可促进蚁群的迁巢、分巢,使蚁巢数量迅速增加。结论红火蚁具有应对降雨的适应行为,这些行为使红火蚁能够在高强度和长时间的降雨中保持种群的生存和繁衍。每年的红火蚁防治应安排在雨季到来之前,此时采取措施压低红火蚁蚁巢密度,能够降低全年红火蚁防控的压力。     

应用沉淀法消除HLAP患者生化标本乳糜状态的探讨

目的探索磷钨酸镁沉淀法在高脂血症性急性胰腺炎(HLAP)患者标本进行生化检验前对重度乳糜状态的消除作用。方法取外观正常标本经磷钨酸镁处理后做各项生化检验,与处理前数据进行相关性分析;以脂肪乳液配制轻、中、重3组模拟乳糜血清做回收试验,计算各生化项目的回收率;收集HLAP患者标本做实证试验,观察乳糜消除效果和生化检验效果。结果除了二氧化碳结合力(CO2CP)、总胆红素(TBil)、直接胆红素(DBil)、肌酸激酶同工酶MB(CK-MB)、乳酸脱氢酶同工酶1(LD-1)、半胱氨酸蛋白酶抑制剂C(Cys C)、高敏C反应蛋白(hs-CRP)外,钾离子(K+)、钠离子(Na+)、氯离子(Cl-)、钙离子(Ca2+)、血糖(Glu)、尿素(Urea)、尿酸(UA)、肌酐(Cr)、淀粉酶(AMY)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、γ-谷氨酰基转移酶(GGT)、碱性磷酸酶(ALP)、胆碱酯酶(CHE)、总蛋白(TP)、白蛋白(Alb)、总胆汁酸(TBA)、肌酸激酶(CK)、乳酸脱氢酶(LD)、α-羟丁酸脱氢酶(α-HBDH)经磷钨酸镁处理后均可正确检测,且与处理前呈高度的直线相关,拟合曲线显著性检验显示P均0.01。回收试验中3组模拟乳糜血清各生化项目的回收率最低为98.03%,最高为103.44%,回收效果良好。HLAP患者标本经磷钨酸镁处理后可正确检测的生化项目与相关性分析实验中外观正常的标本一致,甘油三酯(TG)10 mmol/L或TG40 mmol/L的标本乳糜消除效果明显,TG为10~40 mmol/L的标本需先做稀释使TG10 mmol/L再做处理。结论磷钨酸镁沉淀法清除血脂效果显著,对绝大多数的生化检验不会产生干扰,适用于重度乳糜状态的HLAP患者标本生化检验前的处理。     

2006-2010年成都市气温、降雨量与蚊密度监测

目的分析平均气温与降水量对成都监测点蚊密度监测的影响,为提高国家病媒生物监测质量提供参考。方法使用2006-2010年国家成都病媒监测点蚊密度(诱蚊灯)监测结果,与监测日当旬平均气温与旬旬降水量由SPSS软件计算Spearman秩相关系数,偏相关系数。结果成都蚊密度监测结果与平均气温呈不同程度正相关(r∶0.21-0.91,P∶0.00-0.04),降水量则与蚊密度关系较弱(r∶-0.04-0.59,P∶0.02-0.05)。结论降雨量对蚊密度监测结果有正反两方面影响(r∶-0.32-0.38,P∶0.02-0.04),蚊密度监测需注意规避降雨日。     

Electrocrystallization of calcium carbonate on carbon-based electrodes

Calcium carbonate was deposited by electrochemical reduction of oxygen to hydroxyl ions at various carbon-based electrodes. Although some vaterite was observed during earlier stages of the electrodeposition, the predominant polymorph during later stages was calcite. The average crystal size reached a value of 15 μm after 10 h at a glassy carbon electrode but the crystal growth rate was substantially accelerated when oxygen was catalytically reduced. The same average size of the calcite crystals in this case (Pt/C electrode) was reached within a period of 1.5 h. Efficient removal of CaCO₃ from water was demonstrated when using a porous aerogel carbon electrode and a potential sufficiently negative to promote reduction of water molecules within the pores.     

From Precipitation to Inhibition of Seizures: Rationale of a Therapeutic Paradigm

Summary:  Epileptic seizures can be triggered by both nonspecific facilitating factors such as sleep withdrawal, fever, or excessive alcohol intake, and specific reflex epileptic mechanisms. These consist of sensory or cognitive inputs activating circumscribed cortical areas or functional anatomic systems that, due to some functional instability, respond with an epileptic discharge. Interruption of seizure activity at the stage of the aura (i.e., locally restricted discharge) also can be achieved by nonspecific (e.g., relaxation or concentration techniques or vagal nerve stimulation) or by specific focus-targeted sensory or cognitive inputs. The latter, again, activate circumscribed cortical areas. Intriguingly, in some patients, the same stimulus can either precipitate or abort a seizure. The response depends on the state of cortical activation: seizure precipitation occurs in the resting condition, and seizure interruption occurs when the epileptic discharge has begun close to the activated area. These relations can be understood on the background of experimental data showing that an intermediate state of neuronal activation is a precondition for the generation of paroxysmal depolarization shifts, whereas a hyperpolarized neuron will remain subthreshold, and a depolarized neuron that already produces action potentials is not recruitable for other activity. Sensory input meeting an intermediately activated pool of potentially epileptic neurons is adequate to produce a seizure. In another condition, the same stimulus can depolarize a neuron pool in the same area sufficiently to block the further propagation of nearby epileptic activity. Understanding these interactions facilitates the development of successful nonpharmaceutical therapeutic interventions for epilepsy.     

La nutrition en conditions extrêmes

Nutritional reference intakes are build to cover the nutritional needs of the majority of the “normal“ population in a “normal“ environment. Much work is needed to define references for extreme situations. Beside extreme situations such as pathology, under or over nutrition, the study of other extreme conditions could lead to useful insights in pathophysiological mechanisms. Man adaptation to cold temperatures, altitude or spatial flights leads to the development of experimental models, the utility of which goes far beyond the studied conditions: the regulation of appetite and of the metabolisms of proteins, carbohydrates or calcium provides interesting examples.     

Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation

This study aims to develop amorphous solid dispersion (ASD) of lumefantrine with a cost-effective approach of spray anti-solvent precipitation. Four acidic polymers, hydroxypropylmethylcellulose phthalate (HPMCP), hydroxypropylmethylcellulose acetate succinate (HPMCAS), poly(methacrylic acid–ethyl acrylate) (EL100) and cellulose acetate phthalate (CAP) were studied as excipients at various drug-polymer ratios. Of the studied polymers, satisfactory physical stability was demonstrated for HPMCP- and HPMCAS-based ASDs with no observed powder X-ray diffraction peaks for up to 3 months of storage at 40 °C/75% RH. HPMCP and HPMCAS ASDs also achieved greater drug release levels in the dissolution study than other polymers. The HPMCP-based ASDs with a drug:polymer ratio of 2:8 exhibited a maximum drug release of 140 μg/mL for up to 2 h, which is significantly higher than the currently marketed formulation of Coartem® (<80 ng/mL). Relatively, the CAP and EL100 ASDs indicated a higher water content and crystallized within a day when stored at 40 °C/75% RH. The choice of polymer, and the drug-polymer ratio played a crucial role in the solubility enhancement of lumefantrine. Our study indicates that the developed spray anti-solvent precipitation method could be an affordable approach for producing ASDs.