Synthesized Anti-HER2 Trastuzumab-MCC-DM1 Conjugate: An Evaluation of Efficacy and Cytotoxicity

Background: Trastuzumab is a humanized monoclonal antibody that targets site-specifically human epidermal growth factor-2 receptor (HER2) cell surface antigen overexpressed in approximately 20% of human breast carcinomas. Despite its positive therapeutic outcomes, a large proportion of individuals are unresponsive to the treatment with trastuzumab or develop resistance to it.Objective: To evaluate a chemically synthesized trastuzumab-based antibody-drug conjugate (ADC) to improve the trastuzumab therapeutic index.Methods: The current study explored the physiochemical characteristics of the trastuzumab conjugated to a cytotoxic chemotherapy agent DM1 via Succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) linker, created in our earlier study, using SDS-PAGE, UV/VIS, and RP-HPLC analyses. The antitumor effects of the ADCs were analyzed using MDA-MB-231 (HER2-negative) and SK-BR-3 (HER2-positive) cell lines utilizing in vitro cytotoxicity, viability, and binding assays. Three different formats of a HER2-targeting agent: trastuzumab, synthesized trastuzumab-MCC-DM1, and commercially available drug T-DM1 (Kadcyla®) were compared.Results: UV-VIS spectroscopic analysis showed that the trastuzumab-MCC-DM1 conjugates, on average, entailed 2.9 DM1 payloads per trastuzumab. A free drug level of 2.5% was determined by RP-HPLC. The conjugate appeared as two bands on a reducing SDS-PAGE gel. MTT viability assay showed that conjugating trastuzumab with DM1 significantly improved the antiproliferative effects of this antibody in vitro. Importantly, the evaluations using LDH release and cell apoptosis assays confirmed that trastuzumab maintains its ability to induce cell death response while conjugating with the DM1. The binding efficiency of trastuzumab-MCC-DM1 was comparable to that of the naked trastuzumab.Conclusion: Trastuzumab-MCC-DM1 was found effective against HER2+ tumors. The potency of this synthesized conjugate brings it closer to the commercially available T-DM1

The Role of BCR-ABL P190 in Diagnosis and Prognosis of ALL patients

Acute lymphoblastic leukemia(ALL) is due to early stage arrest of lymphoblast development. The translocation of Philadelphia (Ph) chromosome occurs as a result of the BCR-ABL fusion gene, which constitutively produced activated tyrosine kinase. This gene fusion is an important indicator for prognosis in ALL and is associated with poor overall survival and remission duration. BCR-ABL could interfere in establishment of ALL. Therefore, in this study, we will try to investigate most pathological aspects involved in BCR-ABL fusion. Strategies for genetic alterations in B-ALL pathogenesis are discussed. Then, the main cytogenetic changes and genetic subtypes for ALL are highlighted. Moreover, intermediate reactions between cancer stem cells (CSC) related to ALL, its niche and microenvironment is discussed. The main objective in this review is to understand the principle prognosis in ALL to introduce new approaches and treatment alternatives

Analyzing the Impact of COVID-19 Pandemic on Different Educational Aspects of Surgical Specialties’ Residency Program: A Preliminary Report

Introduction: The lifestyle and learning of trainees from different surgical specialties have been severely affected by the COVID-19 pandemic. Despite the growing body of research, the extent to which their surgical or educational performance is affected is not yet well-understood. We investigated the Iranian multi-specialty surgical residents nationwide to clarify the extent this new pandemic’s has affected their surgical and educational activities. Material and Methods: Our specialized board designed a questionnaire which was sent to residents from the 18th of May to 12th of Jun 2020. The questionnaire comprised demographic data, questions on the clinical, surgical, and educational activities during and before the pandemic. Results: Out of 700 eligible residents, 543 (77%) submitted their answers to all questions. 417 (76.8%) of the respondents declared they had spent their residency program at a hospital that was the main referral center for patients with COVID-19 infection. The weekly number of the outpatient and emergent visits decreased by one third (P<0.001) and one-half (P<0.001), respectively, following the pandemic. Also, the amount of surgeries has dramatically decreased (P<0.001). The median weekly hours devoted to face-to-face activities decreased, while the study time increased and the share of virtual education has a five-fold increase (P<0.001). Conclusion: This pandemic had a significant impact on many aspects of training in surgical specialties’ residency program in Iran. Increasing the time available to study is an opportunity, and online education, despite its challenges, has been effective

Stem Cell Therapy and Its Products Such as Exosomes: Modern Regenerative Medicine Approach

Regenerative Medicine is a developing and multidisciplinary field of science that uses tissue engineering, biology, and cell or cell-free therapy to regenerate cells, tissues, and organs to restore their impaired or lost function. Regenerative medicine uses a new element linked to stem cells, which call exosomes, introduces it to the healthcare market. Exosomes are present in almost all body fluids, such as synovial fluid and blood. Exosomes and microvesicles are very efficient mediators of cell-to-cell communication by transferring their specific cargo to recipient cells. Furthermore, the modification of extracellular vesicles is possible that can become an excellent choice for drug delivery systems and vaccines. Isolation of exosomes for their use as therapeutic, research, or diagnostic agents for a specific type of disease is of particular importance. Five techniques have been used to isolate exosomes from different sources, including ultracentrifugation-based, size-based, immunoassay, exosome sedimentation, and microfluidic techniques. The use of exosomes in medicine has many applications, including in Bone and cartilage, dental, immune system, liver, kidney, skeletal muscle, nervous, heart systems, skin and wound, microbial and infectious, and also in cancers. This chapter focuses on stem cells, especially exosomes, as novel approaches in disease treatment and regenerative medicine

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026

Background The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95$7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the $24·8 billion (95$43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and$37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. Interpretation There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained

Assessment and Analysis Strategies according to Space Matrix-case Study: Petrochemical and Banking Industries in Tehran Stock Exchange (TSE)

AbstractStrategic planning is a three step process including formulation; implementation and review and adjustment. Different tools for formulation step have been introduced yet. SPACE matrix which stands for Strategic Position and Action Evaluation is one of these tools which have gained high reliability for considering macroeconomic, microeconomic and financial factors in the process of determining the position of the organization. On the other hand, Accelerating process of privatization and banking industry development besides petrochemical industry's contribution in Iran's GDP implies that both banking and petrochemical industries are two vital wings of Iran's economic. So, determining the strategic position of these two industries is as similar as a compass for determining the Iran's economic position. The main purpose of this research is to determine and analyze strategic position of three case companies in petrochemical and banking industries in Iran affected by international sanctions by using SPACE matrix method. This research is based on quantitative research approach with a population consisting of non-governmental and governmental banks and petrochemical companies. For data collection, questionnaires and disclosed information on financial statements have been used. Important result of this research is the aggressive position of the three case companies despite of international sanctions on them

Mimicking Mechanical Behavior of Human Tissue with 3D Printable Elastomeric Hydrogel

  Injectable biomaterials are useful for numerous biomedical applications, such as introducing therapeutics into tissues or for 3D printing. Numerous polymeric biomaterials have been developed to mimic the tissue's mechanical properties. however, designing an ideal biomaterial with tunable properties that can mimic different tissue niches remains an unfulfilled promise. Here, an injectable resilin-like elastomeric hydrogel is designed with highly tunable properties, with methacrylate polyurethane as the elastomeric part and hydroxyethyl methacrylate as the hydrogelic part (PUHEMA). Elongation at break (λmax) and Young's module (E) can be controlled by tuning the composition of the elastomeric part. We illustrate how this prototypical polyurethane elastomer enables the replication of the mechanical properties of various tissues.  </p

D3.1 Improved timetable planning

In ARCC project work package 3, research and innovation activities have been done to identify areas with a need for improved timetable planning methods and outline how new methods can be developed and implemented. Improved timetable planning scope were described and there was an activity to connect to other relevant Shift2Rail projects. An workshop was organised in Stockholm 2018-05-29. State of the art in practice was described for timetable planning in Sweden, UIC 406 method and Ansaldo STS Traffic management systems. Also state of the art in algorithms was described. Future work plan research needs areas are: 1. Understanding of various goals for timetabling and how they co-variate 2. Residual capacity 3. Connection and coordination of the planning processes 4. Connection and coordination of the yard/terminal planning and network planning 5. Integration of freight trains into the timetable, focusing on short-term and ad-hoc 6. Integration of maintenance scheduling and timetabling, at all planning stages 7. Improved decision support for handeling of deviations from timetable in operations 8. Features of planning tools, and implementation of automatized timetablingPeterson är "main editor".Övriga författare är "Medarbetare/bidragsgivare".Automated Rail Cargo Consortium: Rail freight automation research activities to boost levels of quality, efficiency and cost effectiveness in all areas of rail freight operation

Comparing the effects of education through compact disk and social media on knowledge and practice regarding the assessment of preterm infant behavior among nurses in neonatal intensive care units

Background: Nurses in neonatal intensive care units (NICUs) need adequate professional knowledge and skills for providing quality developmental care to premature newborns. Objectives: This study aimed to compare the effects of education through compact disk (CD) and social media (SM) on knowledge and practice regarding the assessment of preterm infant behavior (APIB) among nurses in NICUs. Methods:This quasi-experimental study was conducted on fifty NICU nurses. They were randomly allocated to a CD and a SM group. The intervention for both the groups was the same and consisted of education about APIB. Participants' APIB-related knowledge and practice were assessed before and after the intervention using a researcher-made knowledge questionnaire and the APIB checklist, respectively. Data were analyzed through the Chi-square, the independent-samples t, and the paired-samples t-tests as well as the analysis of covariance. Results: The pretest mean scores of knowledge and practice were, respectively, 9.72 ± 4.95 and 207.64 ± 109.49 in the SM group and 9.16 ± 5.94 and 209.88 ± 110.46 in the CD group. After the study intervention, these values significantly increased to 14.80 ± 1.80 and 361.96 ± 38.24 in the SM group (P 0.05), the posttest mean scores of knowledge and practice in the SM group were significantly greater than the CD group (P < 0.05). Conclusion: SM-based education is more effective than CD-based education in improving APIB-related knowledge and practice among NICU nurses