Diabetic retinopathy (DR) is a multifactorial disease displaying vascular-associated pathologies, including vascular leakage and neovascularization, ultimately leading to visual impairment. However, animal models accurately reflecting these pathologies are lacking. Vascular endothelial growth factor A (VEGF-A) is an important factor in the development of micro- and macro-vascular pathology in DR. In this study, we evaluated the feasibility of using a cumate-inducible lentivirus (LV) mediated expression of vegf-a to understand DR pathology in vitro and in vivo. Retinal pigment epithelial cells (ARPE-19) were transduced with cumate-inducible LV expressing vegf-a, with subsequent analysis of vegf-a expression and its impact on cell proliferation, viability, motility, and permeability. Cumate tolerability in adult Wistar rat eyes was assessed as an initial step towards a potential DR animal model development, by administering cumate via intravitreal injections (IVT) and evaluating consequent effects by spectral domain optical coherence tomography (SD-OCT), flash electroretinography (fERG), ophthalmic examination (OE), and immunohistochemistry. Transduction of ARPE-19 cells with cumate-inducible LV resulted in ~ 2.5-fold increase in vegf-a mRNA and ~ threefold increase in VEGF-A protein secretion. Transduced cells displayed enhanced cell proliferation, viability, permeability, and migration in tube-like structures. However, IVT cumate injections led to apparent retinal toxicity, manifesting as retinal layer abnormalities, haemorrhage, vitreous opacities, and significant reductions in a- and b-wave amplitudes, along with increased microglial activation and reactive gliosis. In summary, while cumate-inducible LV-mediated vegf-a expression is valuable for in vitro mechanistic studies in cellular drug discovery, its use is not a feasible approach to model DR in in vivo studies due to cumate-induced retinal toxicity.

People seeking higher privileges or disability benefits are prone to simulate cognitive difficulties (van Oorsouw, Merckelbach, 2010). The most common is the simulation of memory impairment, but there is no adapted test in Lithuania that could identify it. The purpose of this study is to determine Rey Fifteen-Item Test (FIT; Rey, 1964; Lezak, Howieson, Bigler, Tranel, 2012) sensitivity and specificity by comparing three groups of subjects: healthy responders, who perform tests, as usual, healthy responders, who were instructed to simulate memory impairments and patients with traumatic brain injuries. The study included 91 subjects aged 18 to 86 years (M=42.04 SD=13.5). The study used the “Short Term Memory Test” (STMT; Vasserman, Dorofeeva, Meyerson, 1997), the FIT, socio-demographic questions. The results of the study revealed that the malingerers and nonmalingerers did not differ in the STMA scores. Whereas in patients with traumatic brain injuries STMA scores were significantly lower. Nonmalingerers and patients with traumatic brain injuries performed better on FIT than malingerers. The probability that the malingerers score lower than people with memory difficulties is 62 up to 78 percent; FIT sensitivity ranges between 73 and 90 percent, specificity between 41 and 72 percent, depending on the RPOT cut-off score.

Duplication of the '3 days after IVT Control' panel.