Development and approval of live attenuated influenza vaccines based on Russian master donor viruses: Process challenges and success stories

Influenza is a viral infection that affects much of the global population each year. Vaccination remains the most effective tool for preventing the disease. Live attenuated influenza vaccine (LAIV) has been used since the 1950s to protect humans against seasonal influenza. LAIVs developed by the Institute of Experimental Medicine (IEM), Saint Petersburg, Russia, have been successfully used in Russia since 1987.In 2006, the World Health Organization (WHO) announced a Global action plan for influenza vaccines (GAP). WHO, recognizing potential advantages of LAIV over the inactivated influenza vaccine in a pandemic situation, included LAIV in the GAP.BioDiem Ltd., a vaccine development company based in Melbourne, Australia which held the rights for the Russian LAIV, licensed this technology to WHO in 2009. WHO was permitted to grant sub-licenses to vaccine manufacturers in newly industrialized and developing countries to use the Russian LAIV for the development, manufacture, use and sale of pandemic and seasonal LAIVs. To date, WHO has granted sub-licenses to vaccine manufacturers in China (Changchun BCHT Biotechnology Co., Ltd.), India (Serum Institute of India Pvt. Ltd.) and Thailand (Government Pharmaceutical Organization). In parallel, in 2009, IEM signed an agreement with WHO, under which IEM committed to supply pandemic and seasonal candidate vaccine viruses to the sub-licensees.This paper describes the progress made by collaborators from China, India, Russia and Thailand in developing preventive measures, including LAIV against pandemic influenza.     

Impact of new technologies on diabetes care

Technologies for diabetes management, such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) systems, have improved remarkably over the last decades. These developments are impacting the capacity to achieve recommended hemoglobin A1c levels and assisting in preventing the development and progression of micro- and macro vascular complications. While improvements in metabolic control and decreases in risk of severe and moderate hypoglycemia have been described with use of these technologies, large epidemiological international studies show that many patients are still unable to meet their glycemic goals, even when these technologies are used. This editorial will review the impact of technology on glycemic control, hypoglycemia and quality of life in children and youth with type 1 diabetes. Technologies reviewed include CSII, CGM systems and sensor-augmented insulin pumps. In addition, the usefulness of advanced functions such as bolus profiles, bolus calculators and threshold-suspend features will be also discussed. Moreover, the current editorial will explore the challenges of using these technologies. Indeed, despite the evidence currently available of the potential benefits of using advanced technologies in diabetes management, many patients still report barriers to using them. Finally this article will highlight the importance of future studies tailored toward overcome these barriers to optimizing glycemic control and avoiding severe hypoglycemia.     

Crowns cemented on crown preparations lacking geometric resistance form. Part II: effect of cement.

PURPOSE: This study evaluated the effect of different cements on resistance to dislodgment of crowns cemented on preparations lacking geometric resistance form. MATERIALS AND METHODS: A preparation that offered no geometric resistance form, with 20 degrees total occlusal convergence (TOC), 0.9 mm wide shoulder finish line, and a 2.5 mm axial wall height was created on an ivorine tooth using a milling machine. Ten metal test specimen die replicas and 10 standardized metal crowns with recipient sites for the application of external forces through a universal testing machine were fabricated. The crowns were cemented on the dies under 5 and 10 kg external loads, the marginal openings measured, loaded to dislodgment, and cleaned of cement. The process was repeated using zinc oxide and eugenol (ZOE), zinc phosphate (ZPh), resin modified glass ionomer (RMGI), and composite resin (CR) cements. RESULTS: Marginal openings under 5 kg cementation loads were 74.63 (+/-15.04) for ZOE, 75.98 (+/-18.20) microm for ZPh, 98.58 (+/-22.62) microm for RMGI, and 105.82 (+/-20.07) microm for CR cements respectively; under 10 kg cementation loads they were 57.62 (+/-15.86) microm, 59.55 (+/-15.41) microm, 95.00 (+/-19.52) microm, 101.30 (+/-12.52) microm respectively. Oblique dislodgment forces, measured with a Universal testing machine, were 40.18 (+/- 6.76) N for ZOE, 215.65 (+/-45.79) N for ZPh, 165.43 (+/-19.53) N for RMGI, and 181.54 (+/-30.75) N for CR respectively when crowns were cemented under 5 kg loads. The corresponding values for 10 kg loads were 38.62 (+/-4.19), 274.86 (+/-54.22), 139.70 (+/-21.71), and 160.40 (+/-21.21) respectively. Only zinc phosphate cement produced statistically enhanced resistance when crowns were cemented under 10 kg force (p value = 0.035). CONCLUSIONS: Under the conditions of the present study only crowns cemented with zinc phosphate displayed increased resistance to dislodgment on preparations lacking resistance form.     

Complete Axon Arborization of a Single CA3 Pyramidal Cell in the Rat Hippocampus, and its Relationship With Postsynaptic Parvalbumin-containing Interneurons

The complete axon arborization of a single CA3 pyramidal cell has been reconstructed from 32 (60 /μm thick) sections from the rat hippocampus following in vivo intracellular injection of neurobiotin. The same sections were double-immunostained for parvalbumin-a calcium-binding protein selectively present in two types of GABAergic interneurons, the basket and chandelier cells-in order to map boutons of the pyramidal cell in contact with dendrites and somata of these specific subsets of interneurons visualized in a Golgi-like manner. The axon of the pyramidal cell formed 15 295 boutons, 63.8% of which were in stratum oriens, 15.4% in stratum pyramidale and 20.8% in stratum radiatum. Only 2.1% of the axon terminals contacted parvalbumin-positive neurons. Most of these were single contacts (84.7%), but double or triple contacts (15.3%) were also found. The majority of the boutons terminated on dendrites (84.1%) of parvalbumin-positive cells, less frequently on cell bodies (15.9%). In order to estimate the proportion of contacts representing synapses, 16 light microscopically identified contacts between boutons of the filled pyramidal cell axon and the parvalbumin-positive targets were examined by correlated electron microscopy. Thirteen of them were found to be asymmetrical synapses, and in the remaining three cases synapses between the labelled profiles could not be confirmed. We conclude that the physiologically effective excitatory connections between single pyramidal cells and postsynaptic inhibitory neurons are mediated by a small number of contacts, mostly by a single synapse. This results in a high degree of convergence and divergence in hippocampal networks.     

高原地区部队医院谋求新发展应处理好七个关系

从高原部队医院实际出发,阐述了适应新形势谋求新发展应处理好的七个关系:即继承与创新的关系;坚持“姓军为兵的服务方向与对外有偿服务的关系;基础建设与人才建设的关系;日常医疗保障与科研的关系;发挥自身特色与学习借鉴的关系;硬件建设与软件建设的关系;科技研究与成果转化的关系。     

Convergence of occipital nerve and superior sagittal sinus input in the cervical spinal cord of the cat

Co-existence of facial and occipital pain may occur in occipital neuralgia, migraine and cluster headache; suggesting convergence of trigeminal and cervical afferents. Such convergence has been shown in humans and other animals, but the site and extent of this are uncertain. In anaesthetized adult cats, the superior sagittal sinus and occipital nerve were stimulated electrically, and extracellular recordings made in the dorsolateral area of the upper cervical cord using glass-coated tungsten electrodes. Of 49 units in 10 cats, 33 (67%) had input from the superior sagittal sinus and the occipital nerve. Thirteen (27%) had superior sagittal sinus input and 3 (6%) had occipital nerve input. Convergent receptive fields were identified mechanically in 7 units. These experiments in cats show convergent input from occipital nerve and superior sagittal sinus on dorsolateral area units in two-thirds of cases studied. This experimental site of trigeminocervical convergence may relate to referral of pain in occipital neuralgia and other headaches.     

AC/A ratios in myopic and emmetropic Hong Kong children and the effect of timolol§

Purpose: Caucasian children with myopia have elevated response accommodative vergence to accommodation (AC/A) ratios. The purpose of this study was twofold: to determine if response AC/A ratios vary with refractive error and with myopic progression rate in Hong Kong Chinese children, and to determine the effect of beta‐adrenergic antagonism with topical timolol application on AC/A ratios. Methods: Thirty children aged eight to 12 years participated in the study. All refractive errors were corrected with spectacle lenses. Accommodative responses were measured using a Shin‐Nippon autorefractor and concurrent changes in vergence were assessed using a vertical prism and a Howell‐Dwyer card at three metres and 0.33 metre. Accommodative demand was altered using plus or minus two dioptre lenses and lens‐ and distance‐induced response AC/A ratios were calculated. Measurements were repeated 30 minutes after the instillation of topical timolol maleate (0.5 per cent). Results: AC/A ratios appeared higher in progressing myopic children but the difference was not statistically significant. Timolol application reduced accommodative convergence (AC) in the stable myopes (reduction = ‐3 ± 1.14^A) but not in the emmetropes (0.69 ± 0.9^P) or progressing myopes (0.16 ± 0.43^A) and this difference between refractive groups was statistically s ignificant (F^2,27= 3.766; P= 0.036). However, timolol did not produce a significant change in the accommodative response to positive or negative lenses or response AC/A ratios. Conclusions: We did not find that AC/A ratios in myopic Chinese children were elevated and therefore, it is unlikely that elevated AC/A ratios are responsible for the high levels of myopia that occur in Hong Kong. The finding that timolol reduced AC in the stable myopes suggests that the autonomic control of accommodative convergence in these children may be different from that in emmetropic children and those with progressing myopia.     

有助改善人体健康的纳米生物科技

纳米技术是20世纪80年代末期兴起的新技术。此种新技术是指在1-100nm这一尺度范围内对原子和分子运动规律和特性进行研究和应用。通过直接操纵和安排原子、分子将物质转变成具有特殊性能的新材料的科学技术。纳米技术研究的最终目标是直接以原子和分子为起点，从纳米材料出发或采用纳米加工技术，制造出具有特殊功能的产品，从而改变人类的生产和生活模式。纳米科技保健产品对促进人类健康有积极作用。     

Vestibular responses in the Rhesus monkey ventroposterior thalamus. II. Vestibulo-proprioceptive convergence at thalamic neurons

Summary The vestibular thalamic relay in the Rhesus ventrobasal complex, identified in a previous field potential study (part I, Deecke et al., 1974), has now been investigated with neuronal recordings in the thalamus in order to clarify its functional role. In part I, short latency responses (2.5 msec) were found in the corner between VPL, VPM and VPI nuclei, largely including dorsal portions of the VPI nucleus. Field potentials of somewhat longer latency (4–5 msec) were recorded in VPL and in other thalamic nuclei, including the posterior nuclear group.Neuronal responses were recorded in thalamic nuclei of awake flaxedilized Rhesus monkeys. Cells not responding to vestibular stimulation (round window polarisation of either labyrinth) were ignored. The great majority (80%) of those neurons responding to labyrinth polarisation showed convergence with deep somatic (proprioceptive) input from joints and muscles of vertebral column and limbs. 60% of these bimodal neurons responded to movement of cervical joints. Very few vestibularly responsive cells received cutaneous (6.6%), non-optokinetic visual or auditory (2.6% each) input. Proprioceptive fields tended to be large, frequently involving more than one joint, and could be even bilateral. For a few cells the pattern of vestibulo-proprioceptive convergence could be fitted to a coordinated body position that might occur during normal locomotion. 78% of the cells responded to polarisation of both labyrinths, indicating strong bilateral projection.