Moving Knowledge to Action: Aware,Adopt, Adapt (A3)

This article begins with an overview of the knowledge translation (KT) process, introduces commonly used KT terms and the Aware-Adopt-Adapt (A³) KT map. The A³ was created by a nurse practitioner (NP) for practitioners and NP students to provide a map for those who wish to move existing knowledge to practice, yet do not know where to start or do not have the time to take a deeper dive into specific KT theories.     

藏药细叶亚菊的质量标准研究＊

目的 建立细叶亚菊的质量标准，为其质量控制和合理开发利用提供科学参考。方法 采用性状鉴别、显微鉴别、薄层色谱法（TLC）对细叶亚菊进行定性分析；参照《中国药典》（2020年版）通则方法对细叶亚菊水分、总灰分、酸不溶性灰分、水溶性浸出物进行含量检查；利用高效液相色谱法（HPLC）测定细叶亚菊中绿原酸、异绿原酸A的含量。结果 确定了细叶亚菊的药材性状及显微特征。TLC鉴别显示，供试品（细叶亚菊药材）与对照品（绿原酸、异绿原酸A）在相应位置上均显示相同颜色的荧光斑点。13批细叶亚菊水分、总灰分、酸不溶性灰分、浸出物的含量分别为8.55%-13.07%、6.81%-12.68%、1.11%-3.53%、8.41%-11.64%；绿原酸、异绿原酸A的含量范围分别为0.072%-0.440%、0.283%-1.324%（n=3）。结论 本研究建立的方法准确稳定，可为细叶亚菊的质量控制提供参考。暂规定细叶亚菊水分不得过12.0%，总灰分不得过10.0%，酸不溶性灰分不得过2.5%，水溶性浸出物不得少于8.0%，绿原酸不得少于0.2%，异绿原酸A不得少于0.6%。     

A novel CDKN1A-JAZF1 gene fusion in low-grade endometrial stromal sarcoma arising from endometriosis in abdominal wall cesarean section scar: A case report and literature review

ObjectiveWe report a low-grade endometrial stromal sarcoma (ESS) with a novel CDKN1A-JAZF1 fusion gene arising from abdominal wall endometrioma.Case reportA 40-year-old woman presented with a 5.5-cm abdominal wall mass juxtaposed to the postoperative scar of two cesarean sections. Histologically, the tumor exhibited obvious tongue-like protrusions into the surrounding tissue, showed spindle cells with multinodular growth pattern that occasionally rotate around small arteries. Immunohistochemically, the tumor cells were positive for CD10, estrogen receptor (ER), progesterone receptor (PR), negatively stained for smooth muscle actin (SMA), CD117, CyclinD1. In addition, a previously undescribed gene fusion between CDNK1A 5′ end of exon 1(NM_000389.5) and JAZF1 3′ end of exon 5 (NM_175,061,3) was reported in this case.ConclusionThis report of ESS suggesting that rapidly growing abdominal wall masses without menstruation-related should be promptly evaluated and treated aggressively. In addition, we have expanded the molecular landscape of low-grade ESS.     

Update on pediatric corneal diseases and keratoplasty

Managing pediatric corneal disorders is challenging as the prognosis of pediatric keratoplasty depends on several factors. Advancements in the genetic basis of congenital corneal diseases and investigations in congenital corneal conditions provide a better understanding of pediatric corneal conditions. Surgeons performing keratoplasty in children now have a choice of various techniques. Evolving surgical techniques of anterior lamellar and endothelial keratoplasties have expanded the management interventions in these pediatric corneal morbidity conditions; however, considerable concerns still exist in association with corneal transplantation in infants and children. Outcomes in pediatric keratoplasty depend upon the preoperative indications, the timing of surgical intervention, intraoperative and postoperative factors including the patient/care givers’ compliance. Factors such as low scleral rigidity, higher rate of graft failure, need for frequent examinations under anesthesia, and difficulty in optimal visual acuity assessment still remain a considerable challenge in pediatric scenarios. In children, deprivation amblyopia as a result of the corneal opacification can adversely affect visual development, causing dense amblyopia. Outcomes to surgical interventions for management of corneal opacification in children are further compromised by the preexisting amblyopia apart from the concerns of refractive outcome of the graft. Graft rejection, graft infection, amblyopia, and glaucoma continue to be serious concerns. In recent years both anterior and posterior lamellar keratoplasty techniques are being increasingly performed in pediatric eyes, which offer advantages in the form of lower risk of graft rejection. The timing of surgery, careful case selection, cautious intraoperative approach, and optimal postoperative management can improve the anatomical and functional outcome in difficult cases.     

解偶联蛋白1基因多态性与2型糖尿病心脑血管并发症的相关性

目的探讨解偶联蛋白1(UCP1)基因多态性与2型糖尿病(T2DM)心脑血管并发症的相关性。方法选取2019年7月—2020年7月住院治疗的T2DM 440例,根据有无心脑血管并发症分为观察组(T2DM合并心脑血管并发症)221例和对照组(单纯T2DM)219例。比较两组一般资料,UCP1在rs45539933、rs10011540及rs1800592位点的基因型分布与等位基因频率;通过多因素Logistic回归分析评估T2DM发生心脑血管事件的危险因素。结果观察组病程长于对照组,糖化血红蛋白水平高于对照组,而血清高密度脂蛋白胆固醇水平低于对照组(P<0.01)。观察组C/C基因型分布及C碱基频率均高于对照组(P<0.05)。C/C基因型是T2DM患者发生心脑血管并发症的危险因素(P<0.05)。结论UCP1基因多态性与T2DM心脑血管并发症的发生显著相关。     

Cold-passaged isolates and bat-swine influenza a chimeric viruses as modified live-attenuated vaccines against influenza a viruses in pigs

Swine influenza A virus (swIAV) infections in pig populations cause considerable morbidity and economic losses. Frequent reverse zoonotic incursions of human IAV boost reassortment opportunities with authentic porcine and avian-like IAV in swine herds potentially enhancing zoonotic and even pre-pandemic potential. Vaccination using adjuvanted inactivated full virus vaccines is frequently used in attempting control of swIAV infections. Accelerated antigenic drift of swIAV in large swine holdings and interference of maternal antibodies with vaccine in piglets can compromise these efforts. Potentially more efficacious modified live-attenuated vaccines (MLVs) bear the risk of reversion of MLV to virulence. Here we evaluated new MLV candidates based on cold-passaged swIAV or on reassortment-incompetent bat-IAV-swIAV chimeric viruses. Serial cold-passaging of various swIAV subtypes did not yield unambiguously temperature-sensitive mutants although safety studies in mice and pigs suggested some degree of attenuation. Chimeric bat-swIAV expressing the hemagglutinin and neuraminidase of an avian-like H1N1, in contrast, proved to be safe in mice and pigs, and a single nasal inoculation induced protective immunity against homologous challenge in pigs. Reassortant-incompetent chimeric bat-swIAV vaccines could aid in reducing the amount of swIAV circulating in pig populations, thereby increasing animal welfare, limiting economic losses and lowering the risk of zoonotic swIAV transmission.     

A lethal and rare cause of arthrogryposis: Glyt1 encephalopathy

Glycine encephalopathy with normal serum glycine (MIM #617301), also known as GLYT1 encephalopathy, is an extremely rare disorder caused by biallelic variants in SLC6A9 and characterised by facial dysmorphic features, skeletal findings including contractures, knee hyperextension, and joint dislocations and seizures. To date, only ten patients from five families have been reported and only two of them could survive until childhood. In this study, we report on a consanguineous Turkish couple with a history of six pregnancies with three habitual abortions and three postpartum exitus. While in three pregnancies the babies were born prematurely at 32nd gestational week by emergency ceserean section due to hydrops and fetal distress, the other pregnancy was medically terminated at 16th gestational week due to absent fetal heart activity. The product of all these three pregnancies exhibited similar phenotype including short neck, thoracic kyphosis, hypertrichosis, joint contractures and dislocations, hypertonia, knee hyperextension and facial dysmorphic features. Trio exome sequencing was performed prenatally during the last pregnancy and a novel VUS variant in SLC6A9 and a likely pathogenic variant in MTOR gene were detected. DNA isolation was performed from frozen muscle and adrenal tissue of previously autopsied fetuses with similar clinical features, and the same variants were confirmed in both of them. Our data suggest that SLC6A9 and MTOR variants may be responsible for this extremely lethal phenotype in this family.     

Insights into the pathogenesis of ATP1A1‐related CMT disease using patient‐specific iPSCs

The development of patient‐specific induced pluripotent stem cells (iPSCs) offered interesting insights in modeling the pathogenesis of Charcot‐Marie‐Tooth (CMT) disease and thus we decided to explore the phenotypes of iPSCs derived from a single CMT patient carrying a mutant ATP1A1 allele (p.Pro600Ala). iPSCs clones generated from CMT and control fibroblasts, were induced to differentiate into neural precursors and then into post‐mitotic neurons. Control iPSCs differentiated into neuronal precursors and then into post‐mitotic neurons within 6‐8 days. On the contrary, the differentiation of CMT iPSCs was clearly defective. Electrophysiological properties confirmed that post‐mitotic neurons were less mature compared to the normal counterpart. The impairment of in vitro differentiation of CMT iPSCs only concerned with the neuronal pathway, because they were able to differentiate into mesendodermal cells and other ectodermal derivatives. ATP1A1 was undetectable in the few neuronal cells derived from CMT iPSCs. ATP1A1 gene mutation (p.Pro600Ala), responsible for a form of axonal CMT disease, is associated in vitro with a dramatic alteration of the differentiation of patient‐derived iPSCs into post‐mitotic neurons. Thus, the defect in neuronal cell development might lead in vivo to a decreased number of mature neurons in ATP1A1‐CMT disease.