CYTED Network to develop an immunogen compatible with integrated management strategies for tick control in cattle

INCOGARR is a thematic network recently approved to be financially supported by the Ibero-American Program of Science and Technology for Development (CYTED). The objectives of this Network are the design and evaluation of an efficient and feasible anti-tick vaccine candidate from the technical and economical points of view and also sharing experiences in the immunological control of ticks as part of an Integrated Control Program. The Network consists of seven laboratories and one company from six countries. The first meeting of the Network took place with the representation of each laboratory involved. In the meeting, general and specific objectives and activities of the Network were discussed and it was a very nice example of international collaboration to address an unsolved worldwide topic on tick control in which laboratories with different competencies and expertise join their efforts in a common goal.     

美托洛尔对充血性心力衰竭患者心功能、血浆脑钠肽、炎症因子的影响

目的探讨美托洛尔对充血性心力衰竭(CHF)患者心功能、血浆脑钠肽、炎症因子的影响。方法选取2017年6月～2018年6月在我院就诊的充血性心力衰竭患者92例,随机分为观察组和对照组,每组46例,对照组采取常规治疗,观察组在对照组治疗的基础上联合美托洛尔治疗,比较两组治疗前后的疗效、BNP及心功能指标LVEDD、LVESD、LVEF及炎症因子TNF-α、IL-6水平的变化情况。结果观察组患者治疗后显效率达60.8%、总有效率达97.8%,对照组患者治疗后显效率达50.0%、总有效率达74.0%,两组显效率比较,差异无统计学意义(P0.05),两组总有效率比较,差异具有统计学意义(P0.05)。治疗后,观察组患者的LVEDD、LVESD水平显著低于对照组,LVEF水平显著高于对照组,差异具有统计学意义(P0.05)。观察组患者治疗后的BNP水平显著低于对照组,差异具有统计学意义(P0.05)。观察组患者的TNF-α、IL-6水平显著低于对照组,差异具有统计学意义(P0.05)。结论充血性心力衰竭(CHF)患者应用美托洛尔治疗,能够改善其心功能,降低血浆脑钠肽水平,抑制炎症反应,值得临床广泛推广和应用。     

心脏瓣膜置换术围术期患者血浆NT-proBNP水平检测及其预后评估

目的探讨血浆N端脑利钠肽前体(N-terminal pro-brain natriuretic peptide in plasma,NT-proBNP)检测在心脏瓣膜置换术围术期的临床应用及对瓣膜手术患者预后的评估价值,为临床心脏瓣膜置换术提供指导。方法随机抽取2011年6月～2019年6月在我院进行心脏瓣膜置换术的240例患者为观察组,检测其围术期的血浆NT-proBNP水平,另选取30名健康志愿者为对照组,检测对照组血浆NT-proBNP水平,探讨血浆NT-proBNP水平与患者心功能之间的联系及对预后的评估价值。结果手术前后,观察组血浆NT-proBNP水平明显高于对照组,差异有统计学意义(P0.05)。且NT-proBNP水平越高,患者的心功能越低,瓣膜置换术后,观察组患者血浆NT-proBNP水平显著高于手术前,后再逐渐降低并显著低于手术前,发生术后不良事件的患者血浆NT-proBNP浓度水平明显高于未发生不良事件的患者,差异有统计学意义(P0.05)。结论心脏瓣膜病患者的血浆NT-proBNP水平较高,且其血浆NT-proBNP水平越高患者心功能越低,检测其浓度值可作为干预心脏瓣膜病的指标,也可作为瓣膜置换术后的评估指标,对瓣膜置换术患者的预后评估有良好的临床应用价值。     

Proteomic genotyping of fingermark donors with genetically variant peptides

Proteomic genotyping detects single amino acid polymorphisms to infer the genotype of corresponding non-synonymous SNPs. Like any DNA genotype, these inferences can be used to estimate random match probability. Fingermarks are a common source of biological evidence that is sample limited and a highly variable source of identifying DNA. Genetically variant peptides from fingermarks, that contain single amino acid polymorphisms, are an additional source of identifying genetic information. To discover these peptide biomarkers epidermal corneocytes from 9 subjects were isolated, processed, digested with trypsin and applied to mass spectrometry. The resulting proteomic and matching exome datasets were used to discover, characterize and validate 60 genetically variant peptides. An average of 28.8 ± 4.4 genetically variant peptides were detected from each subject resulting in a total of 264 SNP allele inferences with 260 true and 4 false positives, a false discovery rate of 1.5%. Random match probabilities were estimated using the genotype frequencies from the matching major populations in the 1000 Genomes Project. Estimates ranged up to a value of 1 in 1.7 × 10⁸, with a median probability of 1 in 2.4 × 10⁶. Furthermore, the proteomically-inferred genotypes are likely to be compatible with the STR-based random match probability estimates since the closest STR locus was 2.2 Mb from the nearest GVP-inferred SNP. This project represents a novel mode of genetic information that can be obtained from fingermarks and has the potential to complement other methods of human identification including analysis of ridge patterns or touch DNA.     

肾上腺髓质素在呼吸系统相关性疾病中的研究进展

【摘要】 血浆肾上腺髓质素（ADM）是一种具有多种生物学活性的内源性肽,以自分泌、旁分泌和内分泌的方式发挥功能和作用,包括舒张血管、降低血压、扩张支气管平滑肌细胞、改善微循环、稳定血管内皮功能、调节肺动脉压、调节炎症及免疫功能、参与多种激素的分泌和调节等作用,因最初在肾上腺嗜铬细胞瘤组织中发现而得名。后来发现其在多种器官、组织均有表达,包括心、脑、肾、肿瘤组织等,尤其在内皮细胞、血管平滑肌细胞等表达含量较高,在人体肺组织中也广泛存在。目前许多研究已发现肾上腺髓质素可能参与某些肺部疾病的病理生理过程,包括社区获得性肺炎、支气管哮喘、慢性阻塞性肺部疾病、肺动脉高压、肺部肿瘤等疾病。本文就肾上腺髓质素在呼吸系统相关性疾病方面的研究进展作一综述。     

Antimicrobial peptide LL-37 and its pro-form,hCAP18, in desquamated epithelial cells of human whole saliva

The antimicrobial peptide LL-37 is active against oral bacteria and has been demonstrated to be present in human saliva, but its distribution in different fractions of saliva is not known. LL-37 is formed from its intracellular pro-form, hCAP18, in an extracellular enzymatic reaction catalyzed by proteinase 3 and kallikrein 5. Here, we prepared cell-containing and cell-free fractions of unstimulated human whole saliva by centrifugation after depolymerization of mucins with dithiothreitol, and measured the levels of hCAP18/LL-37 in these fractions using ELISA. Cellular expression of hCAP18/LL-37 was determined by western blotting and immunocytochemistry. The ELISA analyses demonstrated that both cells and cell-free saliva contained hCAP18/LL-37. Western blot analysis of cell-pellet homogenates showed a strong band corresponding to hCAP18 at the correct molecular weight and a weak band corresponding to LL-37. Phase-contrast and light microscopy revealed that the cells consisted of desquamated epithelial cells. These cells expressed cytoplasmic immunoreactivity for hCAP18/LL-37. The peripheral part of the cytoplasm, corresponding to the plasma membrane, was particularly rich in hCAP18/LL-37 immunoreactivity. No immunoreactivity was observed after omission of the primary antibody. We conclude that desquamated epithelial cells of human whole saliva contain antimicrobial hCAP18/LL-37, suggesting that these cells may take part in the innate immune system by harboring and releasing these peptides.     

Machine intelligence in peptide therapeutics: A next-generation tool for rapid disease screening

Discovery and development of biopeptides are time-consuming, laborious, and dependent on various factors. Data-driven computational methods, especially machine learning (ML) approach, can rapidly and efficiently predict the utility of therapeutic peptides. ML methods offer an array of tools that can accelerate and enhance decision making and discovery for well-defined queries with ample and sophisticated data quality. Various ML approaches, such as support vector machines, random forest, extremely randomized tree, and more recently deep learning methods, are useful in peptide-based drug discovery. These approaches leverage the peptide data sets, created via high-throughput sequencing and computational methods, and enable the prediction of functional peptides with increased levels of accuracy. The use of ML approaches in the development of peptide-based therapeutics is relatively recent; however, these techniques are already revolutionizing protein research by unraveling their novel therapeutic peptide functions. In this review, we discuss several ML-based state-of-the-art peptide-prediction tools and compare these methods in terms of their algorithms, feature encodings, prediction scores, evaluation methodologies, and software utilities. We also assessed the prediction performance of these methods using well-constructed independent data sets. In addition, we discuss the common pitfalls and challenges of using ML approaches for peptide therapeutics. Overall, we show that using ML models in peptide research can streamline the development of targeted peptide therapies.     

Unknown Tetrahydrocannabinol Edible Ingestion Resulting in Acute Stroke Presentation

BackgroundMarijuana is a commonly used substance in the United States for both recreational and medicinal purposes. Detrimental health-related effects of marijuana continue to be a source of controversy.Case ReportWe describe a case of a woman who presented to the emergency department with acute right upper and lower extremity weakness and altered speech after accidental unknown ingestion of food containing tetrahydrocannabinol (THC). This is a unique case in that we could find no other published report of focal weakness or motor stroke symptoms occurring in the setting of THC ingestion. We will discuss in detail the patient's medical history and timeline of events leading to her presentation to the emergency department. Marijuana contains the psychoactive substance THC and is becoming more commonly used for medicinal and recreational purposes in the United States and abroad. The use of THC is associated with changes in levels of consciousness, perception, and several other physiologic processes. We hope to increase awareness through this case report of accidental THC use by a female patient that resulted in a stroke code and potentially could have led to the use of tissue plasminogen activator.Why Should an Emergency Physician Be Aware of This?To the best of our knowledge, focal neurologic deficits associated with THC use have not been reported in the published literature. We hope that this knowledge will encourage physicians to consider THC intoxication as a cause of new onset extremity weakness.