Predicting the initial spread of novel Asian origin influenza A viruses in the continental USA by wild waterfowl

Using data on waterfowl band recoveries, we identified spatially explicit hotspots of concentrated waterfowl movement to predict occurrence and spatial spread of a novel influenza A virus (clade 2.3.4.4) introduced from Asia by waterfowl from an initial outbreak in North America in November 2014. In response to the outbreak, the hotspots of waterfowl movement were used to help guide sampling for clade 2.3.4.4 viruses in waterfowl as an early warning for the US poultry industry during the outbreak . After surveillance sampling of waterfowl, we tested whether there was greater detection of clade 2.3.4.4 viruses inside hotspots. We found that hotspots defined using kernel density estimates of waterfowl band recoveries worked well in predicting areas with higher prevalence of the viruses in waterfowl. This approach exemplifies the value of ecological knowledge in predicting risk to agricultural security.     

Interleukin-34 drives macrophage polarization to the M2 phenotype in autoimmune hepatitis

BackgroundAutoimmune hepatitis is a chronic inflammatory disease, the abnormal immunological function is the main pathogenesis. Interleukin-34 is a newly identified cytokine that shares the same receptor as colony stimulating factor-1.MethodsWe used interleukin-34 knockout and wild-type mice in a Con A-induced hepatitis model and cocultured RAW264.7 macrophage cells with interleukin-34. We then detected associated inflammatory cytokine and chemokine levels to elucidate the role of interleukin-34.ResultsIn this study, we found that the loss of interleukin-34 resulted in higher sensitivity to Con A-induced hepatitis. RAW264.7 macrophage cells were able to differentiate to the M2 phenotype upon interleukin-34 stimulation.ConclusionsWe conclude that interleukin-34 may protect the liver from Con A-mediated hepatitis by driving M2 macrophage polarization and suppressing inflammation.     

Anatomic feasibility of an endovascular valve–carrying conduit for the treatment of type A aortic dissection

Objective

The study objective was to screen patients with acute type A aortic dissection for anatomic feasibility of ascending aortic endovascular treatment with a valve-carrying conduit.

颈动脉超声联合血清五聚素3、脂蛋白相关磷脂酶A2检测对动脉粥样硬化脑梗死的诊断价值

目的探讨颈动脉超声联合血清五聚素3(PTX3)、脂蛋白相关磷脂酶A2(Lp-PLA2)检测对动脉粥样硬化脑梗死的诊断价值。方法随机选择2015年1月至2017年12月在本院神经内科就诊的急性缺血性脑卒中患者56例作为观察组,选择同期在本院体检的健康者50例作为对照组。2组研究对象均行颈动脉超声检查,并采集静脉血检测PTX3、Lp-PLA2的水平。比较2组血清PTX3、Lp-PLA2水平及颈动脉内膜中膜厚度(IMT)增厚、斑块、中重度狭窄检出率。分析颈动脉超声、PTX3、Lp-PLA2单独及联合检测对动脉粥样硬化脑梗死的诊断价值。结果观察组血清PTX3、Lp-PLA2水平显著高于对照组(P0. 05),颈动脉IMT增厚、斑块、中重度狭窄检出率显著高于对照组(P0. 05)。颈动脉超声联合PTX3、Lp-PLA2检测的灵敏度、准确率为89. 29%、77. 36%,明显高于PTX3(73. 21%、71. 69%)、Lp-PLA2(69. 64%、67. 92%)及颈动脉超声(80. 36%、76. 42%)的单独检测结果(均P0.05)。ROC曲线显示,颈动脉超声检查的曲线下面积(AUC)为0. 789,PTX3检测的AUC为0. 764,Lp-PLA2检测的AUC为0. 776,而联合检测的AUC为0. 909,差异有统计学意义(P0. 05)。结论颈动脉超声联合血清PTX3、LpPLA2检测能够显著提高动脉粥样硬化脑梗死诊断的灵敏度和准确率。     

Clinical features and possible founder mutation of the 8bp duplication mutation in the SLC4A11 gene causing corneal dystrophy and perceptive deafness in three South American families

Background: Corneal Dystrophy and Perceptive Deafness (CDPD) or Harboyan syndrome is an autosomal recessive rare disorder, characterized by congenital corneal opacities and progressive sensorineural hearing loss, which usually begins after the second decades of life. This study reports the ophthalmic, audiological and genetic features, in five CDPD affected patients from three Chilean families.

Materials and Methods: Five individuals affected with CDPD from three unrelated Chilean families were clinically and genetically examined. To evaluate a putative founder mutation 7 SNPs were analyzed in the three families, an Argentinian patient (carrier of the same mutation previously reported) and 87 Chilean controls.

Results: The ophthalmic symptoms in the five patients were bilateral and symmetric, starting before one year of age, and visual acuity varied from 0.1 to 0.3. In all cases, hearing loss began over 8 years old. The sequence of the 19 exons of SLC4A11 gene of all the affected patients exhibited homozygous eight nucleotide sequence duplication (c.2233_2240dup TATGACAC, p.(Ile748Metfs*5)) at the end of exon 16. All the affected patients of the three families were homozygous for a haplotype composed of five SNPs and covering 4,1 Mb. The same haplotype was present in one allele of the heterozygous Argentinean patient and has a frequency of 2.76% in Chilean population.

Conclusions: The five CDPD patients were homozygous for the same mutation in the SLC4A11 gene. Haplotype analysis of all the affected, including the case reported from Argentina was in accordance with a founder mutation.     

Regioselectivity significantly impacts microsomal glucuronidation efficiency of R/S-6, 7-, and 8-hydroxywarfarin

1. Coumadin (R/S-warfarin) metabolism plays a critical role in patient response to anticoagulant therapy. Several cytochrome P450s oxidize warfarin into R/S-6-, 7-, 8-, 10, and 4′-hydroxywarfarin that can undergo subsequent glucuronidation by UDP-glucuronosyltransferases (UGTs); however, current studies on recombinant UGTs cannot be adequately extrapolated to microsomal glucuronidation capacities for the liver.

2. Herein, we estimated the capacity of the average human liver to glucuronidate hydroxywarfarin and identified UGTs responsible for those metabolic reactions through inhibitor phenotyping. There was no observable activity toward R/S-warfarin, R/S-10-hydroxywarfarin or R/S-4′-hydroxywarfarin.

3. The observed metabolic efficiencies (V_max/K_m) toward R/S-6-, 7-, and especially 8-hydroxywarfarin indicated a high glucuronidation capacity to metabolize these compounds.

4. UGTs demonstrated strong regioselectivity toward the hydroxywarfarins. UGT1A6 and UGT1A1 played a major role in R/S-6- and 7-hydroxywarfarin glucuronidation, respectively, whereas UGT1A9 accounted for almost all of the generation of the R/S-8-hydroxywarfarin glucuronide.

5. In summary, these studies expanded insights to glucuronidation of hydroxywarfarins by pooled human liver microsomes, novel roles for UGT1A6 and 1A9, and the overall degree of regioselectivity for the UGT reactions.