SUMMARY
In global health, critical challenges have arisen from infectious diseases, including the emergence and reemergence of old and new infectious diseases. Emergence and reemergence are accelerated by rapid human development, including numerous changes in demographics, populations, and the environment. This has also led to zoonoses in the changing human-animal ecosystem, which are impacted by a growing globalized society where pathogens do not recognize geopolitical borders. Within this context, neglected tropical infectious diseases have historically lacked adequate attention in international public health efforts, leading to insufficient prevention and treatment options. This subset of 17 infectious tropical diseases disproportionately impacts the world's poorest, represents a significant and underappreciated global disease burden, and is a major barrier to development efforts to alleviate poverty and improve human health. Neglected tropical diseases that are also categorized as emerging or reemerging infectious diseases are an even more serious threat and have not been adequately examined or discussed in terms of their unique risk characteristics. This review sets out to identify emerging and reemerging neglected tropical diseases and explore the policy and innovation environment that could hamper or enable control efforts. Through this examination, we hope to raise awareness and guide potential approaches to addressing this global health concern.
Cleavage of heparan sulfate proteoglycans (HSPGs) by the enzyme heparanase modulates tumour-related events including angiogenesis, cell invasion, and metastasis. Metalloshielding of heparan sulfate (HS) by positively charged polynuclear platinum complexes (PPCs) effectively inhibits physiologically critical HS functions. Studies using bacterial P. heparinus heparinase II showed that a library of Pt complexes varying in charge and nuclearity and the presence or absence of a dangling amine inhibits the cleavage activity of the enzyme on the synthetic pentasaccharide, Fondaparinux (FPX). Charge-dependent affinity of PPC for FPX was seen in competition assays with methylene blue and ethidium bromide. The dissociation constant (K ) of TriplatinNC for FPX was directly measured by isothermal titration calorimetry (ITC). The trend in DFT calculated interaction energies with heparin fragments is consistent with the spectroscopic studies. Competitive inhibition of TAMRA-R internalization in human carcinoma (HCT116) cells along with studies in HCT116, wildtype CHO and mutant CHO-pgsA745 (lacking HS/CS) cells confirm that HSPG-mediated interactions play an important role in the cellular accumulation of PPCs.
The COVID‐19 pandemic has produced critical shortages of ventilators worldwide. There is an unmet need for rapidly deployable, emergency‐use ventilators with sufficient functionality to manage COVID‐19 patients with severe acute respiratory distress syndrome. Here, we show the development and validation of a simple, portable and low‐cost ventilator that may be rapidly manufactured with minimal susceptibility to supply chain disruptions. This single‐mode continuous, mandatory, closed‐loop, pressure‐controlled, time‐terminated emergency ventilator offers robust safety and functionality absent in existing solutions to the ventilator shortage. Validated using certified test lungs over a wide range of compliances, pressures, volumes and resistances to meet U.S. Food and Drug Administration standards of safety and efficacy, an Emergency Use Authorization is in review for this system. This emergency ventilator could eliminate controversial ventilator rationing or splitting to serve multiple patients. All design and validation information is provided to facilitate ventilator production even in resource‐limited settings.
We detected no overall changes but did detect different changes at each institution despite the identical intervention. The intervention may be more effective with new faculty and/or smaller discussion sessions. Future steps include refining the rating system, exploring ways to sustain changes, and investigating other factors contributing to feedback quality and utility.
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