One-stage repair of cardiac and arch anomalies without circumlatory arrest

Indian Journal of Thoracic and Cardiovascular Surgery -     

Live Attenuated Influenza Vaccine: Is Past Performance a Guarantee of Future Results?

Live attenuated influenza vaccine (LAIV) has had a tumultuous recent history that can be difficult for many to follow and understand. Prior to 2013, LAIV had a record of accomplishment of providing equal or superior protection against influenza in children. Since 2013, concerns about the lack of protection with LAIV against pandemic H1N1 strains led to the withdrawal of any recommendation for use in the US by the Advisory Committee on Immunization Practices (ACIP). After some significant changes to the content, evaluation and production of LAIV, it has been be recommended again for use in the US in 2018-19. This commentary reviews the origin of LAIV, the events and circumstances that led to the withdrawal of any recommendation for LAIV use by the ACIP, the merits, shortcomings and repercussions of that decision and finally offers some thoughts about the future of LAIV.     

Site-specific regulation of CAV2.2 channels by protein kinase C isozymes βII and ε

Ca_v2.2 high voltage-gated calcium channels are regulated by phorbol-12-myristae, 13-acetate (PMA) via Ser/Thr protein kinase C (PKC) phosphorylation sites in the I–II linker and C-terminus of the α₁ 2.2 subunit. Here we show that PMA enhancement of Ca_v2.2 currents expressed in Xenopus oocytes can be blocked by inhibitors of PKC βII or PKC ε isozymes, as shown previously for Ca_v2.3 currents, and that microinjection of PKC βII or PKC ε isozymes in the oocytes expressing the WT Ca_v2.2 channels increases the basal barium current (I_Ba). The I–V plot shows a large increase in current amplitude with PKC βII and PKC ε isozymes with only a small shift in the peak I_Ba in the hyperpolarizing direction. The potentiation of Ca_v2.2 currents by microinjection of PKC βII and PKC ε isozymes was not altered by the inhibition of G proteins with GDPβS. The combination of isozyme specific inhibitors with previously generated Ser/Thr to Ala mutants of α₁ 2.2 subunit revealed that PKC βII or PKC ε isozymes (but not PKC α or δ) can provide full enhancement through the stimulatory site (Thr-422) in the I–II linker but that PKC ε is better at decreasing channel activity through the inhibitory site Ser-425. The enhancing effect of PKC βII or ε at Thr-422 is dominant over the inhibitory effect at Ser-425. Injected PKC βII also enhances Ca_v2.2 current when any of the potential stimulatory sites (Ser-1757, Ser-2108 and Ser-2132) are available in the C-terminus. PKC ε provides lesser enhancement with C-terminal sites and only with Ser-2108 and Ser-2132. Sites Ser-1757 and Ser-2132, but not Ser-2108, are dominant over the inhibitory site Ser-425. Collectively, these results reveal a hierarchy of regulatory sites in Ca_v2.2 channels. Site-specific regulation by different PKC isozymes may allow graded levels of channel activation and susceptibility or resistance to subsequent stimulatory events.     

L-ficolin binding and lectin pathway activation by acetylated low-density lipoprotein

L-ficolin, like mannan-binding lectin (MBL), is a lectin pathway activator present in normal human plasma. Upon binding ligand, l-ficolin similarly initiates C4 cleavage via the serine protease MBL-associated serine protease-2 (MASP-2). We sought further insight into l-ficolin binding reactions and MASP-2 activation by passing plasma through GlcNAc-derivatized Sepharose. l-Ficolin bound in 1.0 M NaCl-ethylenediamine tetraacetic acid (EDTA), and remained bound in NaCl-free EDTA, while MASP-2 eluted in proenzyme form ( approximately 20% yield, > 40 000-fold purification). L-Ficolin was eluted with GlcNAc in 1.0 M NaCl ( approximately 10% yield, > 3000-fold purification), with trace amounts of C3, alpha(2)-macroglobulin and both native and activated MASP-2. These preparations were utilized to investigate l-ficolin reactivities with acetylated low-density lipoprotein (A-LDL) as a model ligand in albumin-free systems. L-Ficolin bound strongly to A-LDL in the absence as well as presence of calcium, including saline-EDTA, and was optimal in 1.0 M NaCl-EDTA, but binding failed to occur in EDTA in the absence of NaCl. The addition of l-ficolin to immobilized A-LDL resulted in activation of MASP-2 in unmodified but not ficolin-depleted plasma unless l-ficolin was restored. We conclude that A-LDL is a useful ligand for investigation of l-ficolin function; both binding and activation are optimally examined in systems free of albumin; and ligand binding in 1.0 M NaCl in EDTA can be useful in the isolation of l-ficolin and native MASP-2.     

Brighton合作组关于Guillain-Barré综合征的诊断定义和资料收集规范

Guillain-Barr啨综合征(GBS)和Miller Fisher综合征(MFS)的诊断标准随着临床研究的深入在不断演变。2011年1月,《疫苗》杂志发表了国际疫苗安全性监测Brighton合作组关于GBS/MFS的诊断定义和研究资料收集规范。此文献中未采用"诊断标准"而采用"诊断定义"是因为其主要目的为评价疫苗安全性而制定,而非用于神经科的GBS/