Cancer therapies often have narrow therapeutic indexes and involve potentially suboptimal combinations due to the dissimilar physical properties of drug molecules. Nanomedicine platforms could ...address these challenges, but it remains unclear whether synergistic free-drug ratios translate to nanocarriers and whether nanocarriers with multiple drugs outperform mixtures of single-drug nanocarriers at the same dose. Here we report a bottlebrush prodrug (BPD) platform designed to answer these questions in the context of multiple myeloma therapy. We show that proteasome inhibitor (bortezomib)-based BPD monotherapy slows tumour progression in vivo and that mixtures of bortezomib, pomalidomide and dexamethasone BPDs exhibit in vitro synergistic, additive or antagonistic patterns distinct from their corresponding free-drug counterparts. BPDs carrying a statistical mixture of three drugs in a synergistic ratio outperform the free-drug combination at the same ratio as well as a mixture of single-drug BPDs in the same ratio. Our results address unanswered questions in the field of nanomedicine, offering design principles for combination nanomedicines and strategies for improving current front-line monotherapies and combination therapies for multiple myeloma.
Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Co-infection with HIV increases the risk of developing TBM, complicates treatment, and substantially worsens outcome. ...Whether corticosteroids confer a survival benefit in HIV-infected patients with TBM remains uncertain. Hepatitis is the most common drug-induced serious adverse event associated with anti-tuberculosis treatment, occurring in 20% of HIV-infected patients. The suggested concentration thresholds for stopping anti-tuberculosis drugs are not evidence-based. This study aims to determine whether dexamethasone is a safe and effective addition to the first 6-8 weeks of anti-tuberculosis treatment of TBM in patients with HIV, and investigate alternative management strategies in a subset of patients who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy. Methods: We will perform a parallel group, randomised (1:1), double blind, placebo-controlled multi-centre Phase III trial, comparing the effect of dexamethasone versus placebo on overall survival in HIV-infected patients with TBM, in addition to standard anti-tuberculosis and antiretroviral treatment. The trial will be set in two hospitals in Ho Chi Minh City, Vietnam, and two hospitals in Jakarta, Indonesia. The trial will enrol 520 HIV-infected adults. An ancillary study will perform a randomised comparison of three DILI management strategies with the aim of demonstrating which strategy results in the least interruption in rifampicin and isoniazid treatment. An identical ancillary study will also be performed in the linked randomised controlled trial of dexamethasone in HIV-uninfected adults with TBM stratified by LTA4H genotype (LAST ACT). Discussion: Whether corticosteroids confer a survival benefit in HIV-infected patients remains uncertain, and the current evidence base for using corticosteroids in this context is limited. Interruptions in anti-tuberculosis chemotherapy is a risk factor for death from TBM. Alternative management strategies in DILI may allow the safe continuation of rifampicin and isoniazid therapy.
The paper aims to study the factors affecting the decision of international tourists to choose a tourism destination at Hoi An World Cultural Heritage Site. Based on the theory of intended behavior ...integrates new factors: Tourism products; Destination image; and Perceived risk. The research results show that: Using the Theory of Intended Behavior (TPB) with integration with 03 new components in the study of destination choice decisions of international visitors at the Hoi An World Cultural Heritage Site is appropriate; The model achieves composite reliability, discriminant, and extracted variance. The empirical model reached a high level of explaining the variation of variance and the predictive power reached a medium level; Two intermediate structures have been identified in the model, namely Attitude and Destination Image; Affirming the importance of structures has a strong influence on the decision structure of tourist destination selection, namely, perceived risk, social influence, image, and tourism product.
Current anticancer agents suffer from narrow therapeutic indexes and suboptimal therapeutic combinations stemming from mixtures of drugs with dissimilar physical properties. Nanomedicine platforms ...for drug delivery could address these challenges but it remains unclear whether synergistic free drug ratios translate to nanocarriers and whether nanocarriers with multiple drugs outperform mixtures of single-drug nanocarriers at the same dose. Here, we report a bottlebrush prodrug (BPD) platform to answer these questions in the context of multiple myeloma (MM) therapy. We show that a bortezomib-based BPD monotherapy slows tumor progression in vivo and that mixtures of bortezomib, pomalidomide, and dexamethasone BPDs exhibit in vitro synergistic, additive, or antagonistic patterns distinct from the free drug counterparts. BPDs carrying a statistical mixture of 3 drugs in a synergistic ratio outperform the free drug combination at the same ratio and a mixture of single-drug BPDs in the same ratio. Our results address unanswered questions in the field of nanomedicine, offering design principles for combination nanomedicines and strategies for improving current front-line mono- and combination therapies for MM.
The purpose of this study is to examine the factors affecting the development of the night economy in Da Nang city, Vietnam on the basis of a survey of 346 domestic tourists choosing this as a ...tourist destination and participate in night activities and services. The author has synthesized the relevant background theory as well as previous outstanding studies on the issue of tourism development and night economy. SPSS 20 software was used to test the relationship between factors affecting the development of the night economy based on the viewpoints of tourists, residents and local authorities. The results of the study show that 05 factors affect the development of the night economy in Da Nang city in order: The development of a variety of services; Legal and safety regulations; cultural experience opportunities; infrastructure and traffic; service prices. The remaining two factors did not find any influence on the development of the night economy: tourism natural resources; promote and share. The study once again confirms the relationship between the factors affecting the development of the night economy and is a document to help researchers understand better in the research context in Vietnam, one of the leading countries in the world. developing countries and are limited in developing the night economy after the Covid-19 pandemic.
The renovation of current teaching methods aims to achieve two important goals: Firstly, equip students with the ability to synthesize knowledge, skills, etc. in many different fields to solve ...problems. Secondly, from the requirement of educational socialization, it is necessary to fulfill the teaching purposes for all students, that is, to ensure that each individual student is trained to improve knowledge and develop capacity. STEM education is one of the solutions to meet the above goals. STEM education demonstrates integration and differentiation in teaching content and organization to equip learners with necessary knowledge and skills, thereby developing problem-solving abilities for all learners. This article deeply explores the integration and differentiation in the topic of STEM education with the development of problem - solving capacity for students through the topic: Chemical fertilizers in high school grade 11 chemistry program.
On February 27, 2020, the Santa Clara County Public Health Department (SCCPHD) identified its first case of coronavirus disease 2019 (COVID-19) associated with probable community transmission (i.e., ...infection among persons without a known exposure by travel or close contact with a patient with confirmed COVID-19). At the time the investigation began, testing guidance recommended focusing on persons with clinical findings of lower respiratory illness and travel to an affected area or an epidemiologic link to a laboratory-confirmed COVID-19 case, or on persons hospitalized for severe respiratory disease and no alternative diagnosis (1). To rapidly understand the extent of COVID-19 in the community, SCCPHD, the California Department of Public Health (CDPH), and CDC began sentinel surveillance in Santa Clara County. During March 5-14, 2020, four urgent care centers in Santa Clara County participated as sentinel sites. For this investigation, county residents evaluated for respiratory symptoms (e.g., fever, cough, or shortness of breath) who had no known risk for COVID-19 were identified at participating urgent care centers. A convenience sample of specimens that tested negative for influenza virus was tested for SARS-CoV-2 RNA. Among 226 patients who met the inclusion criteria, 23% had positive test results for influenza. Among patients who had negative test results for influenza, 79 specimens were tested for SARS-CoV-2, and 11% had evidence of infection. This sentinel surveillance system helped confirm community transmission of SARS-CoV-2 in Santa Clara County. As a result of these data and an increasing number of cases with no known source of transmission, the county initiated a series of community mitigation strategies. Detection of community transmission is critical for informing response activities, including testing criteria, quarantine guidance, investigation protocols, and community mitigation measures (2). Sentinel surveillance in outpatient settings and emergency departments, implemented together with hospital-based surveillance, mortality surveillance, and serologic surveys, can provide a robust approach to monitor the epidemiology of COVID-19.
The purpose of this study is to examine the factors affecting the publication of sustainability reports from the perspective of managers at 4-5 star hotels in Vietnam. Issues of corporate size, ...profitability, legal regulation, corporate governance and technology of the company were mentioned as factors that may affect the publication of the report on sustainable development. The author has synthesized the relevant background theory as well as previous outstanding studies on the issue of publishing sustainable development reports. SPSS 20 software was used to test the relationship between the factors affecting the publication of the Sustainable Development Report based on the manager's point of view. The results of the study show that the factors of business size, profitability, and legal regulations all affect the publication of sustainable development reports at 4-5 star hotels in Vietnam. A new finding of this study is that the two factors of corporate governance and the company's technology combine into a public governance factor based on technology and it is the technology that has the strongest influence on the publication of the Sustainable Development Report. The study once again confirms the relationship between the factors affecting the publication of the Sustainable Development Report and is a document to help researchers understand better in the research context in Vietnam, one of the leading countries in the world developing countries and have limited access to and use of secondary data.
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