118 research outputs found

    Novel Technology Enables Diagnostic Ultrasound Machine to Treat Hepatocellular Carcinoma in Mice

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    An off-the-shelf diagnostic transducer (ULTRASONIX C5-2) was modified with custom-built circuitry to enable the transducer to produce therapeutic ultrasound in order to ablate hepatocellular carcinomas grown in immunodeficient athymic nude mice (25-35 g; Charles River Laboratories, Wilmington, MA, USA). The therapeutic antivascular ultrasound (AVUS) produced by the off-the-shelf abdominal transducer was unfocused, continuous 2.8MHz ultrasound targeting contrast-enhancing perflutren lipid microbubbles within tumor vasculature. Previous research with a dedicated physiotherapy ultrasound machine (D150 Plus, Dynatronics Corp., Salt Lake City, UT, USA) targeting similar hepatocellular carcinomas showed disrupted tumor neovasculature and irreparable dilation of tumor capillaries with subsequent intercellular edema and hemorrhage.1-3 In this study, the echointensity, peak enhancement (PE), perfusion index (PI), and area under curve (AUC) were measured using non-linear contrast B-mode images acquired before and after the sham or AVUS treatment. These measurements all showed the AVUS produced by the diagnostic transducer markedly decreased tumor blood flow (P \u3c 0.001). In addition, tumor temperature measurement in the live mice showed that AVUS treatment markedly increased tumor temperature with a thermal dose (CEM43) delivered by ultrasound treatment of 124.02 min versus sham of 0 min. Finally, histochemical staining of the tumor samples taken after AVUS treatment revealed several hemorrhagic pools in tumors while the sham-treated tumors lack such hemorrhagic pools. This study demonstrates diagnostic transducers can be enabled to produce AVUS with the ability to target mural hepatocellular carcinomas

    Inclusion in the World Health Organization model list of essential medicines of non-vitamin K anticoagulants for treatment of non-valvular atrial fibrillation: a step towards reducing the burden of cardiovascular morbidity and mortality

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    Non-vitamin K antagonist oral anticoagulants (NOACs) represent a paradigm shift in the treatment of non-valvular atrial fibrillation (AF) with major practice guidelines around the world recommending NOACs over vitamin K antagonist oral anticoagulants for initial treatment of AF for stroke prevention. Here we describe the evidence collated and the process followed for the successful inclusion of NOACs into the 21st WHO Model List of Essential Medicines (EML). Individual NOACs have been reported to be non-inferior or superior to warfarin in preventing stroke and systemic embolism in eligible AF patients with a reduction in the risk of stroke and systemic embolism and a lower risk of major bleeding in patients with non-valvular AF compared with warfarin in both RCTs and real-world data. The successful inclusion of NOACs in the WHO EML is an important step forward in the global fight against cardiovascular morbidity and mortality, especially in low- and middle-income countries, where the burden of disease is high and limited access to diagnosis and treatment translates into a higher burden of morbidity, mortality, and economic costs

    Oral health knowledge, attitudes and practices of people living with diabetes in South Asia : a scoping review

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    Diabetes increases the risk of oral health complications. This review aimed to synthesise the current evidence on the oral health knowledge, attitudes and practices of people living with diabetes in South Asian countries and provide recommendations on possible strategies for addressing the gaps in oral health care in this population, including the role of non-dental professionals. Using a scoping review framework, six electronic databases (Ovid Medline, CINAHL, ProQuest Central, Scopus, Web of Science and Embase) were searched to identify the relevant literature published between January 2000 and December 2021. The data were extracted into three main categories based on the review’s aims, and further refined into sub-categories. A total of 23 studies were included. The review identified that while people with diabetes living in South Asian countries had some level of awareness about oral health and limited care practices to maintain good oral health, there were gaps in knowledge, and there were areas where their oral health practices and attitudes could be improved. The findings suggest a need for developing targeted oral health policies as well as implementing integrated oral health care interventions involving non-dental professionals to improve the oral health outcomes of people with diabetes

    Antiviral Activity of Some Plants Used in Nepalese Traditional Medicine

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    Methanolic extracts of 41 plant species belonging to 27 families used in the traditional medicine in Nepal have been investigated for in vitro antiviral activity against Herpes simplex virus type 1 (HSV-1) and influenza virus A by dye uptake assay in the systems HSV-1/Vero cells and influenza virus A/MDCK cells. The extracts of Astilbe rivularis, Bergenia ciliata, Cassiope fastigiata and Thymus linearis showed potent anti-herpes viral activity. The extracts of Allium oreoprasum, Androsace strigilosa, Asparagus filicinus, Astilbe rivularis, Bergenia ciliata and Verbascum thapsus exhibited strong anti-influenza viral activity. Only the extracts of A. rivularis and B. ciliata demonstrated remarkable activity against both viruses

    Noninvasive genetic population survey of snow leopards (Panthera uncia) in Kangchenjunga conservation area, Shey Phoksundo National Park and surrounding buffer zones of Nepal

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    <p>Abstract</p> <p>Background</p> <p>The endangered snow leopard is found throughout major mountain ranges of Central Asia, including the remote Himalayas. However, because of their elusive behavior, sparse distribution, and poor access to their habitat, there is a lack of reliable information on their population status and demography, particularly in Nepal. Therefore, we utilized noninvasive genetic techniques to conduct a preliminary snow leopard survey in two protected areas of Nepal.</p> <p>Results</p> <p>A total of 71 putative snow leopard scats were collected and analyzed from two different areas; Shey Phoksundo National Park (SPNP) in the west and Kangchanjunga Conservation Area (KCA) in the east. Nineteen (27%) scats were genetically identified as snow leopards, and 10 (53%) of these were successfully genotyped at 6 microsatellite loci. Two samples showed identical genotype profiles indicating a total of 9 individual snow leopards. Four individual snow leopards were identified in SPNP (1 male and 3 females) and five (2 males and 3 females) in KCA.</p> <p>Conclusions</p> <p>We were able to confirm the occurrence of snow leopards in both study areas and determine the minimum number present. This information can be used to design more in-depth population surveys that will enable estimation of snow leopard population abundance at these sites.</p

    Niche-Based Screening in Multiple Myeloma Identifies a Kinesin-5 Inhibitor with Improved Selectivity over Hematopoietic Progenitors

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    SummaryNovel therapeutic approaches are urgently required for multiple myeloma (MM). We used a phenotypic screening approach using co-cultures of MM cells with bone marrow stromal cells to identify compounds that overcome stromal resistance. One such compound, BRD9876, displayed selectivity over normal hematopoietic progenitors and was discovered to be an unusual ATP non-competitive kinesin-5 (Eg5) inhibitor. A novel mutation caused resistance, suggesting a binding site distinct from known Eg5 inhibitors, and BRD9876 inhibited only microtubule-bound Eg5. Eg5 phosphorylation, which increases microtubule binding, uniquely enhanced BRD9876 activity. MM cells have greater phosphorylated Eg5 than hematopoietic cells, consistent with increased vulnerability specifically to BRD9876’s mode of action. Thus, differences in Eg5-microtubule binding between malignant and normal blood cells may be exploited to treat multiple myeloma. Additional steps are required for further therapeutic development, but our results indicate that unbiased chemical biology approaches can identify therapeutic strategies unanticipated by prior knowledge of protein targets
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