Feline immunodeficiency virus (FIV) infection in the cat is a well-evaluated model of human immunodeficiency virus (HIV)-1 infection in man with both viruses associated with significant neuropathology. Although studies in both HIV and FIV infections have shown that virus enters the brain in the acute stages of disease, little is known of the mechanisms of viral entry. The dissection of this stage is fundamental to the development of therapies that may prevent or modulate central nervous system (CNS) infection. The present study was designed to characterize the early sequential neuropathological changes following infection with FIV(GL8), a strain known to enter the CNS in acute infection. Cats were infected either by the intraperitoneal (n = 13) or intravenous (n = 12) route with 2000 cat infectious units of virus. Histopathological assessments following intraperitoneal infections were at 4 (n = 2), 5 (n = 1), 8 (n = 3), 10 (n = 1), 16 (n = 1), 32 (n = 2), 52 (n = 2), and 104 (n = 1) weeks post infection whereas animals infected intravenously were examined (n = 3) at 1, 4, 10, and 23 weeks post infection. The most significant lesions following both routes of infection were lymphocyte-rich perivascular infiltrates within cerebral and cerebellar meninges, in choroid plexus and spinal cord dura mater and within epineurium of the sciatic nerve. In addition, following intravenous infection perivascular infiltrations were noted in parenchymal blood vessels primarily of cerebral white matter. Infiltrates were composed of CD79+ B cells and CD3+ T cells. The latter population contained a mixture of CD4+ and CD8+ cells. The severity of lesions increased in intensity in the 8-to 16-week period following infection and then began to wane. The evaluation of this large group of cats at multiple time points revealed pathology comparable with that of early stage HIV-1-associated encephalitis. Moreover, in contrast to previous FIV neuropathology studies, transient meningeal, choroid plexus, and parenchymal vascular pathology were consistent significant findings suggesting that, as in HIV-1 infection, blood-brain barrier and choroid plexus brain barrier integrity are both compromised in early infection.

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Animal models of human immunodeficiency virus 1, such as feline immunodeficiency virus (FIV), provide the opportunities to dissect the mechanisms of early interactions of the virus with the central nervous system (CNS). The aims of the present study were to evaluate viral loads within CNS, cerebrospinal fluid (CSF), ocular fluid, and the plasma of cats in the first 23 weeks after intravenous inoculation with FIV GL8 . Proviral loads were also determined within peripheral blood mononuclear cells (PBMCs) and brain tissue. In this acute phase of infection, virus entered the brain in the majority of animals. Virus distribution was initially in a random fashion, with more diffuse brain involvement as infection progressed. Virus in the CSF was predictive of brain parenchymal infection. While the peak of virus production in blood coincided with proliferation within brain, more sustained production appeared to continue in brain tissue. In contrast, proviral loads in the brain decreased to undetectable levels in the presence of a strengthening PBMC load. A final observation in this study was that there was no direct correlation between viral loads in regions of brain or ocular tissue and the presence of histopathology.

Background There is a lack of evidence in the literature regarding the learning outcomes of immersive technologies as educational tools for teaching university-level health care students. Objective The aim of this review is to assess the learning outcomes of immersive technologies compared with traditional learning modalities with regard to knowledge and the participants’ learning experience in medical, midwifery, and nursing preclinical university education. Methods A systematic review was conducted according to the Cochrane Collaboration guidelines. Randomized controlled trials comparing traditional learning methods with virtual, augmented, or mixed reality for the education of medicine, nursing, or midwifery students were evaluated. The identified studies were screened by 2 authors independently. Disagreements were discussed with a third reviewer. The quality of evidence was assessed using the Medical Education Research Study Quality Instrument (MERSQI). The review protocol was registered with PROSPERO (International Prospective Register of Systematic Reviews) in April 2020. Results Of 15,627 studies, 29 (0.19%) randomized controlled trials (N=2722 students) were included and evaluated using the MERSQI tool. Knowledge gain was found to be equal when immersive technologies were compared with traditional learning modalities; however, the learning experience increased with immersive technologies. The mean MERSQI score was 12.64 (SD 1.6), the median was 12.50, and the mode was 13.50. Immersive technology was predominantly used to teach clinical skills (15/29, 52%), and virtual reality (22/29, 76%) was the most commonly used form of immersive technology. Knowledge was the primary outcome in 97% (28/29) of studies. Approximately 66% (19/29) of studies used validated instruments and scales to assess secondary learning outcomes, including satisfaction, self-efficacy, engagement, and perceptions of the learning experience. Of the 29 studies, 19 (66%) included medical students (1706/2722, 62.67%), 8 (28%) included nursing students (727/2722, 26.71%), and 2 (7%) included both medical and nursing students (289/2722, 10.62%). There were no studies involving midwifery students. The studies were based on the following disciplines: anatomy, basic clinical skills and history-taking skills, neurology, respiratory medicine, acute medicine, dermatology, communication skills, internal medicine, and emergency medicine. Conclusions Virtual, augmented, and mixed reality play an important role in the education of preclinical medical and nursing university students. When compared with traditional educational modalities, the learning gain is equal with immersive technologies. Learning outcomes such as student satisfaction, self-efficacy, and engagement all increase with the use of immersive technology, suggesting that it is an optimal tool for education.

Alteration of the tight junction complex in renal epithelial cells can affect renal barrier function and perturb normal kidney homeostasis. The immunosuppressant drugs cyclosporine A (CsA) and sirolimus (SRL) used in combination demonstrated beneficial effects in organ transplantation but this combination can also result in increased adverse effects. We previously showed that CsA treatment alone caused an alteration of the tight junction complex, resulting in changes in transepithelial permeability in Madin-Darby canine kidney distal tubular/collecting duct cells. The potential effect of SRL on transepithelial permeability in kidney cells is unknown. In this study, subcytotoxic doses of SRL or CsA were found to decrease the paracellular permeability of the porcine proximal tubular epithelial cells, LLC-PK1 cell monolayers, which was detected as an increase in transepithelial electrical resistance (TER). The cotreatment with SRL and CsA was found to increase TER in a synergistic manner. CsA treatment increased total cellular expression and membrane localization of the tight junction protein claudin-1 and this further increased with the combination of SRL/CsA. SRL and CsA treatment alone or in combination stimulated the phosphorylation of ERK1/2. The MEK-ERK1/2 pathway inhibitor, U0126, reduced the SRL, CsA, and CsA/SRL-induced increase in TER. U0126 also reduced the CsA and CsA/SRL-induced increase in the membrane localization of claudin-1. Alterations in claudin-2 and claudin-4 were also detected. However, the results suggest that the modulation in expression and localization of claudin-1 appears to be pivotal in the SRL- and CsA-induced modulation of the epithelial barrier function and that modulation is regulated by ERK1/2 signaling pathway.