Lower incidence of hospital-treated infections in infants under 3 months of age vaccinated with BCG

BackgroundLive vaccines potentially have non-specific effects that protect against other infections than those the vaccines are targeted against. The national vaccination program (NVP) in Finland was changed on September 1st, 2006: before BCG vaccine was given to all newborn babies and afterwards to babies in risk groups only. We used this natural experiment to study the non-specific effects of BCG in the frame of NVP using before-after design.MethodsWe compared the incidence of several outcomes obtained from Finnish health registers between children born between July 1st, 2004, and June 30th, 2006 (BCG-eligible) and an age- and season-matched reference cohort born between July 1st, 2007, and June 30th, 2009 (BCG-non-eligible) using Poisson regression. These cohorts were restricted to full-term children whose parents were born in Finland. Follow-up began at birth and lasted 3 months, which is the scheduled age for DTaP-IPV-Hib vaccination, and from 4 months until first birthday. The outcomes included all infections, pneumonia and injuries as a negative control outcome.ResultsThe incidence rate ratio (IRR) of the BCG-eligible cohort (N = 93,658) compared to BCG-non-eligible cohort (N = 94,712) for hospital-diagnosed infections was 0.89 (95 %Cl 0.86–0.93) for the 3-month follow-up. The decrease was mainly caused by respiratory infections. In 4–12 months follow-up the BCG-eligible had slightly more infections than BCG-non-eligible children (IRR 1.03, 1.01–1.06).ConclusionsBCG vaccination was associated with a lower incidence of all hospital-diagnosed infections during the first three months of life. The difference cannot be attributed to lung tuberculosis, since only few paediatric cases occurred in Finland during 2000s. The disappearance of non-specific effect after administration of an inactivated vaccine is compatible with previous studies.     

非特异性言语学习障碍的遗传学研究进展

非特异性言语学习障碍是具有明显的遗传倾向和遗传异质性的一类神经心理疾病,患者通常仅具有言语发育障碍这一认知缺陷.研究非特异性言语学习障碍的遗传易感位点和候选基因功能不仅可以从分子角度去认识和理解非特异性言语学习障碍的遗传和病理生理机制,同时也推动了神经心理学和认知遗传学等相关学科的发展.本文就目前常见非特异性言语学习障碍遗传易感位点和候选基因的研究现状及该研究领域所存在和面临的问题,以及发展前景作一综述.     

非特异性相互作用的断裂力与寿命测量

目的　探讨量化非特异性相互作用在特异性选择素－配体分子相互作用中的贡献。方法　利用光镊技术，对牛血清白蛋白(Bovine serum albumin, BSA)封闭的玻璃小球间的非特异性作用进行了系统测量，得出不同加载率下的断裂力以及不同外力作用下的寿命分布。结果　实验结果表明，非特异性作用同样表现出断裂力随加载率增加而增大的趋势。在较低加载率下，非特异性断裂力与选择素－配体特异性断裂力大小、增大趋势基本一致；随着加载率增加，二者的差别逐渐显著，前者的断裂力增加速率远低于后者。同样外力作用下，非特异性作用的寿命平均值比特异性作用要小；不同外力作用下，非特异性作用的寿命随外力增大仅略有下降，与特异性作用中逆锁键－滑移键转化现象有明显不同。结论　该研究结果将为正确评估非特异性相互作用对选择素－配体特异性相互作用实验结果的影响提供基础。     

Effects of ATP antagonists on purinoceptor-operated inward currents in rat phaeochromocytoma cells

The effects of suramin, reactive blue 2 (RB2) and d-tubocurarine (d-TC) were investigated electrophysiologically to elucidate the mechanisms underlying their antagonism of P₂ purinoceptor-mediated responses. All three compounds inhibited an adenosine triphosphate (ATP)-activated inward current in rat phaeochromocytoma PC12 cells in a concentration-dependent manner. The order of potency was RB2 > suramin > d-TC. The inhibition induced by suramin or RB2 was reversible, whereas that induced by d-TC was not reversed after a 5-min rinse. The inactivation of the ATP-activated current was accelerated by d-TC but not by suramin or RB2. RB2 administered simultaneously with ATP exerted much weaker inhibition compared to that induced by prior administration, suggesting that RB2 is a slowly acting antagonist. This was not observed for suramin or d-TC. Suramin and RB2 caused a parallel shift in the concentration/response curve for the ATP-activated current. With d-TC the maximal response of ATP was decreased but the concentration producing half-maximal response was unchanged. The voltage dependency of the ATP-activated current showed less inward rectification in the presence of d-TC. Suramin or RB2 did not affect the voltage dependency. These results suggest that suramin and RB2 reversibly block binding of ATP to receptors, whereas d-TC blocks ion permeability through the ATP-activated channel.     

Evidence for a displaceable non-specific [3H]neurotensin binding site in rat brain

Summary Levocabastine is a potent antihistamine drug, structurally unrelated to neurotensin. In rat and mouse brain but not in other animal species, it inhibited 60% of the [³H]neurotensin binding displaced by unlabelled neurotensin or neurotensin (8–13).The levocabastine-sensitive site or site 1 displayed high affinity properties for levocabastine (IC₅₀=25 nM) and was highly stereospecific (IC₅₀-value higher than 10 M for one of the isomers). Binding to the site 1 in rat brain corresponded to the [³H]neurotensin binding displaceable by 1 M levocabastine, whereas binding to the site 2 corresponded to the binding displaced by 1 M neurotensin when the site 1 was occluded by 1 M levocabastine.Both site 1 and site 2 appeared to be saturable. Scatchard plots obtained in rat bulbus olfactorius allowed to calculate a K _D-values of 7.1 nM and a B _max-values of 37.2 fmol/mg original tissue for site 1, while site 2 displayed a K _D-value of 0.7 nM and a B _max-value of 16.3 fmol/mg original tissue. The regional distributions of both sites showed marked differences. The site 1 was homogeneously distributed throughout all rat brain areas, whereas the amount of site 2 binding was markedly different in separate brain areas: bulbus olfactorius and substantia nigra had the highest amounts (8.9 and 7.8 fmol/mg tissue) while cerebellum had the lowest (0.4 fmol/mg tissue).In spite of its high affinity and stereospecificity, site 1 has to be considered as an acceptor or recognition site for [³H]neurotensin because of its species-link, low saturability and homogeneous distribution in all rat brain areas.On the other hand, site 2 had the characteristics of a physiological receptor: high affinity, saturability in the low nanomolar range and marked regional distribution in rat brain. Site 2 corresponds therefore most probably to the physiological neurotensin receptor. The foregoing experiments provide evidence for the presence of a drug displaceable, non-specific (=unrelated to a physiological receptor) neurotensin binding site in rat brain; levocabastine should be an important tool to occlude this site in order to reveal, by means of in vitro binding assays, the specific neurotensin binding site in rat brain.     

A Theoretical Model for the Margination of Particles within Blood Vessels

The margination of a particle circulating in the blood stream has been analyzed. The contribution of buoyancy, hemodynamic forces, van der Waals, electrostatic and steric interactions between the circulating particle and the endothelium lining the vasculature has been considered. For practical applications, the contribution of buoyancy, hemodynamic forces and van der Waals interactions should be only taken into account, whilst the effect of electrostatic and steric repulsion becomes important only at very short distances from the endothelium (1–10 nm). The margination speed and the time for margination t_s have been estimated as a function of the density of the particle relative to blood , the Hamaker constant A and radius R of the particle. A critical radius R_c exists for which the margination time t_s has a maximum, which is influenced by both and A: the critical radius decreases as the relative density increases and the Hamaker constant decreases. Therefore, particles used for drug delivery should have a radius smaller than the critical value (in the range of 100 nm) to facilitate margination and interaction with the endothelium. While particles used as nanoharvesting agents in proteomics or genomics analysis should have a radius close to the critical value to minimize margination and increase their circulation time.     

Campaigns with oral polio vaccine may lower mortality and create unexpected results

Three studies from Guinea-Bissau found conflicting effects of OPV-at-birth (OPV0) on child survival. One study from 2004 suggested excess male mortality among children receiving OPV0 compared with children receiving NoOPV0 during a period of shortage of OPV. However, two subsequent studies showed beneficial effects of OPV0. In 2004, two national OPV-campaigns had been conducted in Guinea-Bissau. In a reanalysis of the 2004-study, in a survival analysis the age-adjusted mortality rate of study participants was 67% (95% CI = 42–81%) lower after the OPV-campaigns than before the campaigns. In the OPV0 group only 22% (655/3031 person-years (pyrs)) of follow-up time was “after” the OPV-campaigns whereas 55% (473/859 pyrs) of the time in the NoOPV0 group was post-campaign (p < 0.0001, Chi²). Censoring for OPV-campaigns in the original study removed excess male mortality and made the three studies more homogeneous. Overall, there is now considerable evidence that OPV, like other live vaccines, has important beneficial non-specific effects.     

Effects of movement impairment based treatment in the management of mechanical neck pain

Background

Neck pain is a common musculoskeletal complaint in computer users due to prolonged static or awkward work postures. It has been shown that pathogenesis of neck pain is associated with scapular movement impairment syndromes. However, there is a dearth of literature in treatment based on these syndromes.

The impact of childhood vaccines on bacterial carriage in the nasopharynx: a longitudinal study

Background

There is increasing evidence that childhood vaccines have effects that extend beyond their target disease. The objective of this study was to assess the effects of routine childhood vaccines on bacterial carriage in the nasopharynx.

Methods

A cohort of children from rural Gambia was recruited at birth and followed up for one year. Nasopharyngeal swabs were taken immediately after birth, every two weeks for the first six months and then every other month. The presence of bacteria in the nasopharynx (Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus) was compared before and after the administration of DTP-Hib-HepB and measles-yellow fever vaccines.

Results

A total of 1,779 nasopharyngeal swabs were collected from 136 children for whom vaccination data were available. The prevalence of bacterial carriage was high: 82.2% S. pneumoniae, 30.6%, S.aureus, 27.8% H. influenzae. Carriage of H. influenzae (OR = 0.36; 95% CI: 0.13, 0.99) and S. pneumoniae (OR = 0.25; 95% CI: 0.07, 0.90) were significantly reduced after measles-yellow fever vaccination; while DTP-Hib-HepB had no effect on bacterial carriage.

Conclusions

Nasopharyngeal bacterial carriage is unaffected by DTP-Hib-HepB vaccination and reduced after measles-yellow fever vaccination.     

手法联合核心稳定训练治疗老年非特异性腰痛临床研究

目的:观察手法联合核心稳定训练治疗老年非特异性腰痛的临床疗效。方法:124例随机分为研究组和对照组各62例。两组均行手法治疗,观察组加用核心稳定训练治疗。结果:治疗后两组VAS、ODI评分均较治疗前改善(P<0.01),观察组改善程度优于对照组(P<0.01)。治疗后两组闭眼单脚站立时间、闭目原地踏步时间均较治疗前延长(P<0.01),观察组延长程度大于对照组(P<0.05)。结论:手法可以瞬间纠正腰椎“骨错缝、筋出槽”,恢复力学平衡。配合核心稳定性训练,使筋强骨健,维持腰椎稳定,疗效较好且安全。