A Proposal for an Alternative Approach to Particle Size Method Development During Early-Stage Small Molecule Pharmaceutical Development

Particle size analysis in the pharmaceutical industry has long been a source of debate regarding how best to define measurement accuracy; the degree to which the result of a measurement or calculation conforms to the true value. Defining a “true” value for the size of a particle can be challenging as the output of its measurement will differ because of variations in measurement approaches, instrumental differences and calculation methods. Consequently, for “real” particles, a universal “true” value does not exist and accuracy is therefore not a definable characteristic. Accordingly, precision is then a measure of the ability to reproducibly achieve a measurement of unknown relevance.This article proposes, in place of accuracy, a means to define the “appropriateness” of a measurement in line with the critical quality attributes (CQA) of the material being characterized. The decision as to whether the measurement is correct should involve a link to the CQA; that is, correlation should be demonstrated, without which the measured particle size cannot be defined as a critical material attribute.Correspondingly, methods should also be able to provide sufficient precision to demonstrate discrimination relating to variation in the CQA. The benefits and challenges of this approach are discussed.     

Synergism through combination of chemotherapy and oxidative stress-induced autophagy in A549 lung cancer cells using redox-responsive nanohybrids: A new strategy for cancer therapy

A combination of various therapeutic approaches has emerged as a promising strategy for cancer treatment. A safe and competent nano-delivery system is thus in urgent demand to facilitate the simultaneous transport of various therapeutic agents to cancer cells and a tumor region to achieve synergistic effect. Gold nanoparticles (GNPs) and mesoporous silica nanoparticle (MSNs) were fabricated herein as potential candidates for drug delivery. Serving as gatekeepers, GNPs (5 nm in diameter) were attached onto the amino-functionalized MSNs (denoted as NMSNs) via a relatively weak gold–nitrogen bonding. The resulting nanohybrids (denoted as GCMSNs) were uptaken by cells, and the detachment of GNPs and subsequent intracellular drug release from NMSNs were achieved by competitive binding of intracellular glutathione to GNPs. In addition to the function of gatekeeping, GNPs also play another role as the oxidative stress elicitor. Our in vitro studies revealed that GCMSNs induced higher oxidative stress in lung cancer cells (A549) than in normal cells (3T3-L1). This growth inhibitory effect found in the cancer cells was likely induced by mitochondria dysfunction originated from the GCMSN-induced, oxidative stress-triggered mitochondria-mediated autophagy. The redox-responsive nanohybrids were further loaded with camptothecin and the intensified synergistic therapeutic effects were observed associated with combined chemotherapy and oxidative stress strategy. The results clearly demonstrate that such unique nanohybrids hold great promise for selective and effective cancer treatments.     

Interventions to respond to COVID 19 pandemic in Mumbai and way forward

With the emergence of COVID 19 pandemic, the approach used by Municipal Corporation of Greater Mumbai (MCGM) was based on all guidelines of COVID 19 prepared by Ministry of Health and Family Welfare (MoHFW). However, Mumbai undertook a special innovate model used in the mission Mumbai – Dharavi for COVID 19. Additionally, MCGM undertook a proactive approach of “chasing the virus” with its 4Ts: 1. Tracing 2. Tracking 3. Testing 4. Treating in high-risk slum clusters and it reflects the result of declining the incidence and case fatality due to COVID 19. Establishing public health surge capacities which include active surveillance, contact-tracing and follow-up besides early detection, isolation and management of cases are important steps for fighting the COVID 19 pandemic. Collaborating with all partners and setting up a Task force for establishing clinical management protocols was unmissable.     

Long-term skeletal stability in the treatment of mandibular prognathism with a physiological positioning strategy

Our aim was to evaluate the long-term skeletal stability of the mandible in 21 patients after orthognathic surgery with physiological positioning. The measurement points SNB, B point (X, Y), Pog (X, Y), and the angle of the ramus were measured on cephalometric photographs to assess skeletal stability preoperatively, immediately after operation, and one and two years postoperatively. In addition, we evaluated the clinical symptoms of disorders of the temporomandibular joint (TMJ). The analysis of the cephalometric photographs showed that SNB, B point X, and Pog X showed no significant differences among the postoperative time points. On the other hand, B point Y and Pog Y showed no significant differences throughout the study period. We compared the angle of the ramus before operation and two years postoperatively, and no significant difference was found. In addition, no cases showed any pathological symptoms of disorders of the TMJ two years postoperatively. The long-term stability after orthognathic surgery with physiological positioning was confirmed, and it seems to be a reliable orthognathic treatment in patients with mandibular prognathism.     

试论医学院校的转型和发展战略

我国医学院校的发展道路有通过“强强联合”并入综合性大学和通过学科多样化“转型”为多科性大学两种类型。“转型”方式虽然不受广泛的关注，却正在低调而广泛地运行，成为独立设置医学院校自我发展和提高的主要方式。转型期医学院校在发展战略上有明显共性，如专业学科布局的优化、大力扶植基础学科、整合临床资源凸显医学主体、校园规划和建设体现多科性大学的包容性等，应予以重视。     

Preparation of protected peptidyl thioester intermediates for native chemical ligation by Nα‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry: considerations of side‐chain and backbone anchoring strategies,and compatible protection for N‐terminal cysteine*,†

Abstract: Native chemical ligation has proven to be a powerful method for the synthesis of small proteins and the semisynthesis of larger ones. The essential synthetic intermediates, which are C‐terminal peptide thioesters, cannot survive the repetitive piperidine deprotection steps of N^α‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry. Therefore, peptide scientists who prefer to not use N^α‐t‐butyloxycarbonyl (Boc) chemistry need to adopt more esoteric strategies and tactics in order to integrate ligation approaches with Fmoc chemistry. In the present work, side‐chain and backbone anchoring strategies have been used to prepare the required suitably (partially) protected and/or activated peptide intermediates spanning the length of bovine pancreatic trypsin inhibitor (BPTI). Three separate strategies for managing the critical N‐terminal cysteine residue have been developed: (i) incorporation of N^α‐9‐fluorenylmethoxycarbonyl‐S‐(N‐methyl‐N‐phenylcarbamoyl)sulfenylcysteine [Fmoc‐Cys(Snm)‐OH], allowing creation of an otherwise fully protected resin‐bound intermediate with N‐terminal free Cys; (ii) incorporation of N^α‐9‐fluorenylmethoxycarbonyl‐S‐triphenylmethylcysteine [Fmoc‐Cys(Trt)‐OH], generating a stable Fmoc‐Cys(H)‐peptide upon acidolytic cleavage; and (iii) incorporation of N^α‐t‐butyloxycarbonyl‐S‐fluorenylmethylcysteine [Boc‐Cys(Fm)‐OH], generating a stable H‐Cys(Fm)‐peptide upon cleavage. In separate stages of these strategies, thioesters are established at the C‐termini by selective deprotection and coupling steps carried out while peptides remain bound to the supports. Pilot native chemical ligations were pursued directly on‐resin, as well as in solution after cleavage/purification.     

留置超滑乳胶气囊导尿管并发症的原因分析及对策

目的探讨留置超滑乳胶气囊导尿管并发症的原因及对策。方法对586例留置超滑乳胶气囊导尿管患者进行观察,回顾分析。结果留置超滑导尿管并发症与导尿方法、规范操作、留置导尿管的时间及相关知识宣教有关。结论严格无菌操作,选择合适的导尿管、缩短留置尿管的时间是降低并发症的重要措施。     

现代医院组织形象塑造

未来医院的生存竞争不再是某一方面、某一层次的竞争，而是全方位、整体性的组织形象6寺竞争。如何塑造医院的良好形象已成为重要的课题。塑造医院形象最为重要的是在以下环节：树立“品牌经营”的管理理念；实现优质服务，形成各自的服务特色；利用现代营销手段成功实现医院组织形象的推广。使之得到社会公众的认可和支持。     

论现代医院技术创新

创新是医院发展主题,本文采用综合分析、收集资料、对比方法,对技术创新内容、技术创新原则、技术创新趋势进行了较详细的分析研究.     

医学生"网络成瘾症"产生的原因和对策

文章针对目前医学生“网络成瘾症”的现状进行了分析,并指出了产生的原因和解决问题的办法,以求达到标本兼治。最后提出三点预防医学生“网络成瘾症”的对策：一是高校及其附属医院要为医学生营造宽松愉快的学习、生活环境;二是呼吁家长关注医学生身心发展的特殊规律,建立良好的家庭环境;三是建立和完善与网络社会相应的法律法规,规范医学生的网上行为。