Hedgehog pathway inhibition as a therapeutic target in acute myeloid leukemia

Introduction: The Hedgehog (HH) pathway constitutes a collection of signaling molecules which critically influence embryogenesis. In adults, however, the HH pathway remains integral to the proliferation, maintenance, and apoptosis of adult stem cells including hematopoietic stem cells.

Areas covered: We discuss the current understanding of the HH pathway as it relates to normal hematopoiesis, the pathology of acute myeloid leukemia (AML), the rationale for and data from combination therapies including HH pathway inhibitors, and ultimately the prospects that might offer promise in targeting this pathway in AML.

Expert opinion: Efforts to target the HH pathway have been focused on impeding this disposition and restoring chemosensitivity to conventional myeloid neoplasm therapies. The year 2018 saw the first approval of a HH pathway inhibitor (glasdegib) for AML, though for an older population and in combination with an uncommonly-used therapy. Several other clinical trials with agents targeting modulators of HH signaling in AML and MDS are underway. Further study and understanding of the interplay between the numerous aspects of HH signaling and how it relates to the augmented survival of AML will provide a more reliable substrate for therapeutic strategies in patients with this poor-risk disease.     

Respecting the circle of life: one year outcomes from a randomized controlled comparison of an HIV risk reduction intervention for American Indian adolescents

Potential for widespread transmission of HIV/AIDS among American Indian (AI) adolescents exists, yet no evidence-based interventions (EBIs) have been adapted and evaluated with this population. Intensive psychoeducation may improve knowledge and decision-making which could potentially translate to reductions in HIV risk behaviors. A peer group randomized controlled comparison of an adapted EBI vs. control was delivered over an eight-day summer basketball camp in one reservation-based tribal community to adolescents ages 13–19. Outcome data were gathered immediately post-camp and at 6 and 12 months follow-up. Self-selected peer groups were randomized to intervention (n = 138) or control (n = 129) conditions for a total sample of 267 participants (56.2% female), mean age 15.1 years (SD = 1.7). Intervention participants had better condom use self-efficacy post-camp (Adjusted Mean Difference [AMD] = ?0.75, p < 0.005) and at 6 (AMD = ?0.44, p < 0.005) and 12 months (AMD = ?0.23, p < 0.05) follow-up. Intervention participants also had higher HIV prevention and transmission knowledge (post-camp: AMD = 0.07, p < 0.01; 6 months: AMD = 0.06, p < 0.01) were more likely to believe condoms prevent sexually transmitted infections (post-camp: RR = 1.41, p < 0.005; 6 months: RR = 1.34, p < 0.05), to talk with an adult about HIV/AIDS (post-camp: RR=1.78, p < 0.005; 6 months: RR = 1.14, p < 0.005), had higher partner negotiation efficacy related to substance use during sex (post-camp: AMD = 0.37, p < 0.01), and were more likely to intend to use a condom (post-camp: RR = 1.39, p < 0.01). The adapted intervention had short- and medium-term impacts on AI adolescent risk for HIV/AIDS, but attenuated at 12 months. Intervention delivery through a community-based camp is feasible and acceptable with strong retention. Additional study is needed to evaluate the adapted intervention's impact on sexual risk behaviors and if booster sessions and parent involvement translate to long-term impacts.     

Bibliometric analysis of orthopaedic related publications by Indian authors from the last decade

PurposeBibliometric studies have been established methods of analysing publications on a particular topic. These studies have been done on various orthopaedic topics and are increasing. The advantages of these studies have been highlighted in previous publications. Although some studies have been done on Indian publications from other specialties, those analysing Indian Orthopaedic Publications are lacking.MethodsWe performed a search in Scopus to look for all publications related to orthopaedics from India. Our search strategy in Scopus included ((TITLE-ABS-KEY(Orthopaedics OR Orthopaedics) AND AFFIL(India)) AND PUBYEAR > 2009 AND PUBYEAR < 2020) which resulted in 3270 articles on 02/11/2021. We analyzed the most publishing universities, city, state, specialty, authors, and anatomic location of these publications. We also mined the data to draw word clouds based on data obtained from the titles of articles, keywords and the affiliations of each of the articles published.ResultsTamil Nadu and New Delhi and their institutes appear to be the epicenter of publication activities in Orthopaedics in India. There has been a healthy trend of growth of articles in the orthopaedic specialty. Since there is a significant overlap of technology and engineering, it is not surprising to see engineering and technology institutes among the top 10 published institutes and even journals for the publications on orthopaedics.ConclusionThere has been a steady increase in the number of publications in the last decade. New Delhi and its Universities and Institutes appear to contribute the majority of citations and publications related to orthopaedics. Journal of Clinical Orthopaedics and Trauma was the most publishing journal for Indian authors on Orthopaedic related articles.     

藿香正气汤抑制新型冠状病毒复制过程的有效成分及机制初探＊

目的 收集藿香正气汤的主要活性成分，通过分子对接及网络药理学探讨其防控新型冠状病毒肺炎（COVID-19）的有效成分及治疗机制。方法 通过基于配体-蛋白质相互作用的计算方法，以瑞德西韦为对照，探索藿香正气汤潜在治疗COVID-19的成分，并选出对接较好成分进行药理学机制预测，初探其药理学机制。结果 本研究筛选出5种与新冠病毒3CLpro结合能力强于瑞德西韦的小分子成分。网络药理学初步预测抗病毒途径可能是通过PI3K-Akt 信号通路影响病毒复制。结论 成分C1-C5与3CLpro结合良好，推测其可能是潜在的3CLpro的抑制剂，为抗病毒天然药物的开发提供了理论依据。     

Is the autophagy a friend or foe in the silver nanoparticles associated radiotherapy for glioma？

Malignant glioma is the most common intracranial tumor with a dismal prognosis. The radiosensitizing effect of silver nanoparticles (AgNPs) on glioma both in vitro and in vivo had been demonstrated in the previous studies of our group. However, the underlying mechanism is still unclear. Consistent with previous studies, a size and dose dependent antitumor effect and significant radiosensitivity enhancing effect of AgNPs were observed in our experiment system. We also found that cell protective autophagy could be induced by AgNPs and/or radiation, which was verified by the use of 3-MA. The mechanism through which had autophagy and the enhancement of radiosensitivity taken place was further investigated with inhibitors of ERK and JNK pathways. We demonstrated that ERK and JNK played pivotal roles in the radiosensitivity enhancement. Inhibiting ERK and JNK with U0126 and SP600125 respectively, we found that the autophagy level of the cells treated with AgNPs and radiation were attenuated. Moreover, SP600125 down-regulated the apoptosis rate of the co-treated cells significantly. Taken together, the present study would have important impact on biomedical applications of AgNPs and clinical treatment for glioma.     

鞘磷脂类信号通路与动脉粥样硬化的研究进展

动脉粥样硬化是临床常见的冠心病和脑梗死等缺血性心脑血管疾病的主要病理基础,其病因复杂,发病机制尚未完全阐明。近年来,越来越多的研究显示鞘磷脂类信号通路可通过调节脂代谢、炎症和血管内皮功能等影响动脉粥样硬化的发生发展。文章综述了鞘磷脂类信号通路关键分子鞘磷脂、神经酰胺和1-磷酸鞘氨醇与动脉粥样硬化的关系,旨在为防治疾病提供新思路。     

Complications in patients of acetabular fractures and the factors affecting the quality of reduction in surgically treated cases

IntroductionAcetabulum fractures, though relatively uncommon, are associated with significant morbidity and mortality. These involve high energy trauma and due to their complex nature, the management requires understanding the relevant surgical anatomy, defining the injury via appropriate radiographic assessment and determining a suitable treatment plan. Literature is scarce for the demographic data, fracture patterns, associated injuries, management and early complications in the Indian scenario. These factors play a pivotal role in the ultimate recovery of the patients. Therefore this study was conceptualised to assess the epidemiology and evaluate the complications of these fractures. Furthermore the effects of various factors determining the quality of reduction in surgically treated patients were also assessed.MethodologyThis was a prospective observational study in which patients presenting to the advance trauma centre of our institute with acetabulum fractures were included. Demographical data of the patients, mechanisms of injuries, fractures morphologies, complications and radiological outcomes were recorded prospectively.Results116 patients with acetabular fractures were included in the study. 81% of these were males, with average age of 39.95 ± 15.87 years; with road traffic accidents being the predominant mode of injuries. Mortality was reported in 5 patients; 4 patients had deep venous thrombosis and sciatic nerve injuries were seen in 12 patients of which 4 were iatrogenic. 8 patients had some form of infection, out of which 4 required multiple debridements. 4 cases developed heterotrophic ossification while 2 cases had loss of reduction. The timing of surgery and other associated fractures had significant effect on the quality of reduction (p < 0.05); while age, gender, mode of injury or individual fracture patterns had no such effect.ConclusionsProper radiological assessment and evaluation of fracture configuration is important for management of acetabulum fractures. When indicated, this should be followed by early open reduction and internal fixation to achieve anatomical reduction, with management of associated injuries for better outcomes.     

Inter-ictal assay of peripheral circulating inflammatory mediators in migraine patients under adjunctive cervical non-invasive vagus nerve stimulation (nVNS): A proof-of-concept study

Objective

To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.