Epidemiology of Van der Woude syndrome from mutational analyses in affected patients from Pakistan

Malik S, Kakar N, Hasnain S, Ahmad J, Wilcox ER, Naz S. Epidemiology of Van der Woude syndrome from mutational analyses in affected patients from Pakistan. Mutations in IRF6 cause Van der Woude syndrome (VWS), one of the most common syndromes associated with cleft lip (CL) with or without cleft palate (CP). The presence of pits on the lower lip of patients is the most characteristic feature of the syndrome. We have identified three novel and seven previously reported IRF6 mutations in 12 of 16 unrelated families segregating VWS from Pakistan. The three newly identified mutations include a frameshift (c.568delG) and two missense mutations c.295G>A (p.G99S) and c.1219T>C (p.S407P). Recent functional studies on IRF6 and the three‐dimensional structure of IRF5 carboxy (C) terminus, a protein encoded by a paralog of IRF6, shed light on the p.S407P substitution. Additionally, the identification of the same mutations responsible for VWS in Pakistan, as reported in other global populations worldwide, marks these residues as mutational hotspots and indicates their essential role in structural stability or function of IRF6. This is the first study of VWS in Pakistan and we estimate that 1 in 100 patients with CL with or without CP (CL/P) are affected in the Pakistani population predominantly from the Punjab area.     

横断面调查在抗菌药物管理PDCA中的应用

目的：探讨将横断面调查应用于抗菌药物管理PDCA中的成效。方法：通过2012年连续4次横断面调查收集资料,应用于抗菌药物管理PDCA循环的计划与检查环节。结果：调查的8项指标中6项有显著改善（P〈0．01）,其余两项无显著改善（P〉0．05）。结论：将横断面调查应用于抗菌药物管理PDCA的各个环节,能改善抗菌药物临床合理应用状况,是提高抗菌药物管理质量行之有效的方法。     

新疆护理专职教师工作压力现状及影响因素

目的探讨新疆护理教师工作压力现状并分析其影响因素,为提出护理教师队伍建设的相关对策提供实证依据并为护理院校管理和教师人才队伍的可持续发展提出建议。方法采用高职教师工作压力量表对新疆15个地、市、州抽取的10所护理院校在编在岗的256位护理教师进行问卷调查,调查其工作压力现状并分析其影响因素。结果护理专职教师的工作压力得分为（2．436±0．576）分,大于2分,说明教师的工作压力大。教龄、婚姻、兼职情况及教学工作量不同的教师因社会因素而产生的工作压力水平不同,不同婚姻状况的教师因学校管理及制度因素产生的压力水平不同,性别、年龄、学历、婚姻、教学工作量不同的教师个人职业发展所带来的压力水平不同,性别、教龄、每周课时量等在护理院校教师工作压力不同;年龄、婚姻状况、教学工作量不同的教师因人际关系产生的工作压力水平不同,性别、年龄、教龄、职称、婚姻、教学工作量、收入水平及兼职情况不同的教师因工作负荷压力水平不同,性别、职称、婚姻、教学工作量、担任教学课程不同的教师因个人特质因素带来的工作压力不同,差异均有统计学意义（P〈0．05）。结论护理专职教师的工作压力大,来源是多方面的,学校管理制度和社会因素带来的压力最大,因此应尽快改变社会各界对护理教育认识上的不足和偏见,明确护理教育的定位,加大国家对护理教育的投入,同时护理教师应提高对自己职业的认识,合理制定自己的职业生涯发展规划。     

Tumor neoantigens: building a framework for personalized cancer immunotherapy

It is now well established that the immune system can recognize developing cancers and that therapeutic manipulation of immunity can induce tumor regression. The capacity to manifest remarkably durable responses in some patients has been ascribed in part to T cells that can (a) kill tumor cells directly, (b) orchestrate diverse antitumor immune responses, (c) manifest long-lasting memory, and (d) display remarkable specificity for tumor-derived proteins. This specificity stems from fundamental differences between cancer cells and their normal counterparts in that the former develop protein-altering mutations and undergo epigenetic and genetic alterations, resulting in aberrant protein expression. These events can result in formation of tumor antigens. The identification of mutated and aberrantly expressed self-tumor antigens has historically been time consuming and laborious. While mutant antigens are usually expressed in a tumor-specific manner, aberrantly expressed antigens are often shared between cancers and, therefore, in the past, have been the major focus of therapeutic cancer vaccines. However, advances in next-generation sequencing and epitope prediction now permit the rapid identification of mutant tumor neoantigens. This review focuses on a discussion of mutant tumor neoantigens and their use in personalizing cancer immunotherapies.     

The 56-kilodalton major protein antigen of Rickettsia tsutsugamushi: molecular cloning and sequence analysis of the sta56 gene and precise identification of a strain-specific epitope.

Lasting immunity against Rickettsia tsutsugamushi, the causative agent of scrub typhus fever, has been demonstrated to be strain specific. Two protein antigens of 110 and 56 kilodaltons (kDa) have been shown to exhibit strain-specific epitopes. The 56-kDa scrub typhus antigen (Sta56) is an abundant outer membrane protein of R. tsutsugamushi and is an antigen often recognized by humans infected with this obligate intracellular bacterium. In this study the complete gene encoding Sta56 (strain Karp) was cloned into pBR322 on a 2.3-kilobase genomic HindIII DNA fragment and the complete 56-kDa polypeptide was expressed in Escherichia coli. DNA sequence analysis of the 2.3-kilobase HindIII fragment revealed an open reading frame large enough to encode a 56-kDa polypeptide. A putative signal sequence was identified at the deduced amino terminus of the Sta56 polypeptide, and pulse-chase analysis of maxicells labeled with [35S]methionine demonstrated that a higher-molecular-weight precursor matures into the 56-kDa polypeptide. Epitope scanning analysis with synthetic peptides derived from the deduced amino acid sequence identified an octapeptide (located from amino acid residues 117 to 124) that was reactive with a Karp strain-specific monoclonal antibody (K13F88A). Other epitopes recognized by different monoclonal antibodies, including another Karp strain-specific monoclone (K1E106), were localized to different regions of the protein based on their reactivities with lambda gt11 recombinants expressing various portions of the sta56 gene.     

Management of noncardiovascular comorbidities in patients with heart failure with reduced ejection fraction

Patients with heart failure with reduced ejection fraction often have one or more noncardiovascular comorbidities. The presence of concomitant disease states is associated with worse outcomes, including increased risk of mortality, decreased quality of life, and increased healthcare resource utilization. Additionally, the presence of heart failure with reduced ejection fraction complicates the management of these comorbidities, including varying safety and efficacy of therapies compared to those without heart failure. This article will review the literature on the pharmacologic management of common noncardiovascular comorbidities—including chronic obstructive pulmonary disease, depression, diabetes mellitus, gout, chronic kidney disease, and iron deficiency—in patients with heart failure with reduced ejection fraction, as well as provide recommendations for appropriate treatment selection in this population.