Structures of the free and inhibitors-bound forms of bromelain and ananain from Ananas comosus stem and in vitro study of their cytotoxicity

The Ananascomosus stem extract is a complex mixture containing various cysteine ​​proteases of the C1A subfamily, such as bromelain and ananain. This mixture used for centuries in Chinese medicine, has several potential therapeutic applications as anti-cancer, anti-inflammatory and ecchymosis degradation agent. In the present work we determined the structures of bromelain and ananain, both in their free forms and in complex with the inhibitors E64 and TLCK. These structures combined with protease-substrate complexes modeling clearly identified the Glu68 as responsible for the high discrimination of bromelain in favor of substrates with positively charged residues at P2, and unveil the reasons for its weak inhibition by cystatins and E64. Our results with purified and fully active bromelain, ananain and papain show a strong reduction of cell proliferation with MDA-MB231 and A2058 cancer cell lines at a concentration of about 1 μM, control experiments clearly emphasizing the need for proteolytic activity. In contrast, while bromelain and ananain had a strong effect on the proliferation of the OCI-LY19 and HL-60 non-adherent cell lines, papain, the archetypal member of the C1A subfamily, had none. This indicates that, in this case, sequence/structure identity beyond the active site of bromelain and ananain is more important than substrate specificity.

Impact of mechanical simulator practice on clinical ERCP performance by novice surgical trainees: a randomized controlled trial

Background Lack of forward-viewing endoscopy experience impairs training in endoscopic retrograde cholangiopancreatography (ERCP). We evaluated the effect of ERCP mechanical simulator (EMS) practice on ERCP performance by surgical trainees. Patients and methods 12 surgical trainees without endoscopy experience were randomly allocated to non-EMS (n = 6) programs or to EMS (n = 6) programs with coaching and 20 hours of supervised EMS practice. All trainees then received supervised hands-on clinical ERCP training. Trainers provided verbal instructions and hands-on assistance, and took over if cannulation was not achieved by 20 minutes. Blinded trainers rated clinical performance. Results Each group performed 150 clinical ERCPs. Biliary cannulation success was significantly higher in the EMS vs. the non-EMS group (P = 0.006), with shorter mean times (in minutes) for intubation, cannulation, and completion (all P < 0.001). EMS trainees showed a significantly better mean performance score (P = 0.006). In multivariate analysis, after adjusting for case sequence, CBD stone, complexity, and EMS training, the effect of EMS practice on odds for successful cannulation remained highly significant (odds ratio [OR] 2.10 [95 %CI 1.46 – 3.01]). At 6 months EMS trainees still had better cannulation success vs. non-EMS controls (P = 0.045); no difference was observed after 1 year. Conclusions EMS practice shortens the ERCP early learning curve of inexperienced surgical trainees, improves clinical success in selective biliary cannulation, and may reduce complications.

Designing a Mobile-Based Self-Care Application for Patients with Cutaneous Leishmaniasis: An Effective Step in Patients’ Self-Care and Participation

Introduction: Today, the introduction of smartphones into the healthcare field has led to rapid growth in application development; provided many important tasks such as maintaining health and access to information, communications and counseling, referral and data collection, management and supervision of patients; and facilitated patient self-care and participation.Material and Methods: In order to design a mobile-based self-care application, the designing purpose was first defined and then related literature was reviewed and different kinds of software designed in this field were identified. Using the specified information elements, UML diagrams (Use-Case, Sequence, and Activity) were plotted by Visual Paradigm Enterprise 8 software.In fact, a feasibility assessment was carried out, based on which the application prototype was developed and provided to 10 patients to achieve their opinions. In the next step, the final application components were determined based on user feedback and experts approval. In the final step, Quiz Satisfaction Survey Questionnaire v.7.0 was used to assess users' satisfaction.Results: Based on user questions and answers, and answers available in the database, the application offers appropriate therapies that emphasize the presence of patients in health centers.Conclusion: The presented application helps with providing rapid information and awareness about different aspects of the disease.

Interactive Customer Relationship Management Jasa Infrastruktur Jaringan PT. Meda Cipta Hutama

PT. Meda Cipta Hutama merupakan penyedia jasa IT dan general contractor. Keinginan perusahaan adalah memenuhi kebutuhan pelanggan, di mana diperlukan sebuah sistem informasi yang interaktif. Untuk memenuhi keinginan pelanggan tersebut, dibutuhkan sistem informasi Interactive Customer Relationship Management (i-CRM). I-CRM merupakan suatu usaha untuk menciptakan interaksi antara pelanggan dan perusahaan dengan waktu respon yang tinggi sehingga tidak terjadi kesalahan dalam proses persiapan sampai kepada penyajiannya. Metode pengumpulan data menggunakan metode observasi, wawancara, kuesioner dan studi literatur. Sedangkan metode pengembangan sistem informasinya menggunakan model RAD, yang meliputi UML, dengan diagram use case, sequence class, statechart dan activity. Tujuan pada penelitian ini adalah membangun sistem informasi interactive customer relationship management (i-CRM). Adapun hasil yang diperoleh dari penelitian ini berupa sebuah website i-CRM di mana pihak perusahaan dapat berinteraksi langsung dengan pelanggan dan pelanggan juga dapat dengan mudah melakukan purchase order. Selain itu, i-CRM ini dapat meningkatkan pelayanan yang diberikan yang berdampak pada meningkatnya kepuasan dan loyalitas pelanggan. Sistem ini juga dapat mempermudah perusahaan berinteraksi langsung dengan pelanggan menggunakan fasilitas suggestion dan complain, chatting dan newsletter.

PERANCANGAN PROGRAM APLIKASI PEMBELAJARAN IPA MATERI SISTEM PERNAPASAN BERBASIS MULTIMEDIA UNTUK SISWA SDLB BAGIAN B TUNA RUNGU MENGGUNAKAN OBJECT ORIENTED APPROACH

Tunarungu, samahalnya dengan difabel yang lain yang merupakan warganegara Indonesia berhak memperoleh pendidikan. Seperti diketahui Anak Berkebutuhan Khusus (ABK) membutuhkan perhatian lebih untuk meningkatkan fokus terhadap proses belajar. Saat ini dalam kegiatan belajar mengajar di objek penelitian yaitu SDLB Bagian (B) Cidendo Bandung dilakukan secara konvensional, dimana guru menjelaskan materi pelajaran menggunakan buku sebagai alat bantu dalam pengajaran. Keterbatasan media alat bantu yang tepat untuk mengajaranak tuna rungu menjadi masalah bagi para guru untuk mampu menjelaskan materi pelajaran yang dibebankan kepada siswa. Terutama pada mata pelajaran IPA/Sains yang cukup komplek, contohnya materi sistem pernapasan pada manusia dan hewan sangat membutuhkan bantuan alat yang lebih ke arah visual. Untuk mengatasi hal tersebut, dalam penelitian ini dibuatlah rancangan program aplikasi alat bantu pembelajaran IPA/Sains untuk SDLB bagian B khususnya materi sistem pernapasan manusia dan hewan menggunakan metode penelitian Research Development, metode pendekatan berbasis objek (object-oriented approach), dengan alat bantu perancangan menggunakan Unified Modeling Language (UML) yaitu Use Case, Sequence Diagram, Class Diagram.Sedangkan model pengembangan sistem menggunakan prototype. Rancangan tersebut meliputi rancangan proses, rancangan user interface program aplikasi yang disesuaikan dengan aplikasi berbasis multimedia. Berdasarkan rancangan tersebut, nantinya diharapkan dapat diimplementasikan menggunakan software Adobe Flash Cs3 Proffesional yang berbasiskan multimedia, dimana dengan multimedia memungkinkan suatu materi yang tidak dapat disampaikan secara verbal atau kejadian, dapat direkayasa sedemikian rupa sehingga bisa disajikan dengan terperinci dan sangat menarik bagi siswa. Kata kunci: anak berkebutuhan khusus (ABK), tunarungu, IPA/sains, sistem pernapasan manusia dan hewan.

All World Media: a new business model (cases A and B)

Synopsis This failure case study tells the story of All World Media, a start-up offering internet-based media planning and buying tool created by ambitious Estonian entrepreneurs in 2011. A few years earlier the two founders had come up with an idea that in their opinion would revolutionize the process of media planning and buying for advertisers. They had noticed that the industry worked in an intransparent and inefficient way. Based on their own extensive experience in various internet ventures and following first consultations with key industry players they were confident that the market was ready for a self-service online media marketplace. Research methodology The (A) case focusses on the initial business idea and on the events before the launch of the internet platform. The case includes the entrepreneurs' concept, the main contents of the business plan, and the operational steps until the launch of the service on the market. The (B) case outlines the events after the launch of the online service, analyzes the possible reasons for the failure of the original business model and discusses potential strategic alternatives that are still open for the entrepreneurs. Relevant courses and levels The two-case sequence can be used for a 90-minutes session in marketing, entrepreneurship or strategic management courses in graduate and executive programs. The case is accompanied by an instructor's manual which also includes suggested assignment questions and proposed session plan.