+61 7 3365 3098; fax +61 7 3365 1766.Running title: Chronic complications in the STZ rat Key words: Diabetes, echocardiography, electrophysiology, neuropathic pain, cataracts, retinopathy Short abstract:The chronic complications of diabetes in humans include cardiomyopathy, neuropathic pain, cataract development and retinopathy. The rat is the most commonly used model of human disease. This study has determined whether chronic diabetes induced by streptozotocin in rats mimics the complications associated with human diabetes. 1 Abstract:Background: Diabetes in humans induces chronic complications such as cardiovascular

We investigated whether inhibition of platelet-derived growth factor (PDGF) receptor tyrosine kinase activity would affect pericyte viability, vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor-2 (VEGFR-2) expression and angiogenesis in a model of retinopathy of prematurity (ROP). ROP was induced in Sprague Dawley rats by exposure to 80% oxygen from postnatal (P) days 0 to 11 (with 3 hours/day in room air), and then room air from P12-18 (angiogenesis period). Shams were neonatal rats in room air from P0-18. STI571, a potent inhibitor of PDGF receptor tyrosine kinase, was administered from P12-18 at 50 or 100 mg/kg/day intraperitoneal (i.p.). Electron microscopy revealed that pericytes in the inner retina of both sham and ROP rats appeared normal; however STI571 induced a selective pericyte and vascular smooth muscle degeneration. Immunolabeling for caspase-3 and alpha-smooth muscle cell actin in consecutive paraffin sections of retinas confirmed that these degenerating cells were apoptotic pericytes. In all groups, VEGF and VEGFR-2 gene expression was located in ganglion cells, the inner nuclear layer, and retinal pigment epithelium. ROP was associated with an increase in both VEGF and VEGFR-2 gene expression and blood vessel profiles in the inner retina compared to sham rats. STI571 at both doses increased VEGF and VEGFR-2 mRNA and exacerbated angiogenesis in ROP rats, and in sham rats at 100 mg/kg/day. In conclusion, PDGF is required for pericyte viability and the subsequent prevention of VEGF/VEGFR-2 overexpression and angiogenesis in ROP.

Health Technology Assessment (HTA), a tool for priority setting, has emerged as a means of ensuring the sustainability of a Universal Health Coverage (UHC) system. However, setting up an effective HTA system poses multiple challenges and knowledge exchange can play a crucial role in helping countries achieve their UHC targets. This article reports the results of the discussion during a preconference session at the 2019 HTAsiaLink Conference, an annual gathering of HTA agencies in Asia, which supports knowledge transfer and exchange among HTA practitioners. As part of this discourse, 3 main HTA challenges were identified based on experiences of selected countries in Asia and Africa, namely Bhutan, Kenya, Thailand, and Zambia: availability of funding, building technical capacity, and achieving buy-in among stakeholders for successful translation of HTA research into UHC policy. The potential solutions identified through this South-South engagement included establishing a legal mandate for HTA, building local technical capacity through partnerships and enhancing strategic communication with stakeholders to increase awareness, among others. South-South Knowledge Exchange can therefore be instrumental in sharing lessons learned from common challenges and offer potential solutions to address capacity building initiatives for HTA in LMICs.

Public health emergencies (PHEs), such as the COVID-19 crisis, are threats to global health and public order. We recommend that countries bolster their PHE responses by investing in health technology assessment (HTA), defined as a systematic process of gathering pertinent information on and evaluating health technologies from a medical, economic, social and ethical standpoint. We present examples of how HTA organizations in low- and middle-income countries have adapted to supporting PHE-related decisions during COVID-19 and describe the ways HTA can help the response to a PHE. In turn, we advocate for HTA capacity to be further developed globally and for increased institutional acceptance of these methods as a building block for preparedness and response to future PHEs. Finally, the long-term potential of HTA in strengthening health systems and embedding confidence and transparency into scientific policy should be recognized.

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