Int. J. Transl. Med., Volume 2, Issue 1 (March 2022) – 10 articles

The ongoing COVID-19 pandemic continues to affect the lives, wellbeing, and stability of communities worldwide. The race to save human lives is critical, and the development of useful translational animal models to elucidate disease pathogenesis and prevention, and to test therapeutic interventions, is essential to this response. However, significant limitations exist with the currently employed animal models that slow our ability to respond to the pandemic. Non-human primates serve as an excellent animal model for SARS-CoV-2 disease and interventions, but the availability of these animals is scarce, and few facilities are able to house and utilize this model. Adapted murine models are accessible and improving but lack natural hACE-2 receptors and are only moderate representatives of human COVID-19 disease, transmission, and immune responses. On the other hand, there are several animal species that are both naturally and experimentally infected, such as domestic cats, hamsters, ferrets, and mink. Several of these have proven animal-to-animal transmission and evidence of significant clinical and histopathologic disease that mimics acute COVID-19 in humans. Mobilizing these nontraditional animal models could have a crucial role in SARS-CoV-2 research efficiency and impact. This review focuses on what is known about these nontraditional animal models, including their immune responses to SARS-CoV-2 infection, evidence of clinical and histopathologic disease, transmission potential, and the practicality of each model in a research setting. Comparative insight into these animal models for COVID-19 can strengthen the efforts to mitigate this pandemic. Full article

Parkinson’s disease (PD) is the second most common neurodegenerative disease clinically characterized by classical motor symptoms and a range of associated non-motor symptoms. Due to the heterogeneity of symptoms and variability in patient prognosis, the discovery of blood biomarkers is of utmost importance to identify the biological mechanisms underlying the different clinical manifestations of PD, monitor its progression and develop personalized treatment strategies. Whereas studies often rely on motor symptoms alone or composite scores, our study focused on finding relevant molecular markers associated with three clinical models describing either motor, cognitive or emotional symptoms. An integrative multiblock approach was performed using regularized generalized canonical correlation analysis to determine specific associations between lipidomics, transcriptomics and clinical data in 48 PD patients. We identified omics signatures confirming that clinical manifestations of PD in our cohort could be classified according to motor, cognition or emotion models. We found that immune-related genes and triglycerides were well-correlated with motor variables, while cognitive variables were linked to triglycerides as well as genes involved in neuronal growth, synaptic plasticity and mitochondrial fatty acid oxidation. Furthermore, emotion variables were associated with phosphatidylcholines, cholesteryl esters and genes related to endoplasmic reticulum stress and cell regulation. Full article

There are growing numbers of infants and children living with single-ventricle congenital heart disease (SV). However, cardiac dysfunction and, ultimately, heart failure (HF) are common in the SV population and the ability to predict the progression to HF in SV patients has been limited, primarily due to an incomplete understanding of the disease pathogenesis. Here, we tested the hypothesis that non-invasive circulating metabolomic profiles can serve as novel biomarkers in the SV population. We performed systematic metabolomic and pathway analyses on a subset of pediatric SV non-failing (SVNF) and failing (SVHF) serum samples, compared with samples from biventricular non-failing (BVNF) controls. We determined that serum metabolite panels were sufficient to discriminate SVHF subjects from BVNF subjects, as well as SVHF subjects from SVNF subjects. Many of the identified significantly dysregulated metabolites were amino acids, energetic intermediates and nucleotides. Specifically, we identified pyruvate, palmitoylcarnitine, 2-oxoglutarate and GTP as promising circulating biomarkers that could be used for SV risk stratification, monitoring response to therapy and even as novel targets of therapeutic intervention in a population with few other options. Full article

Background: Critical COVID-19 patients account for 1.7 to 13% of all pregnant COVID-19 patients. Methods: Patients admitted to the COVID-19 intensive care unit of Elena Doamna Obstetrics and Gynecology University Hospital in Iasi between 1 January and 1 December 2021, with critical forms of the disease, were included and retrospectively studied. The patients’ age range was 25–44 years in the Alpha group (n = 12) and 27–52 years in the Delta group (n = 9). Results: Most critically ill pregnant COVID-19 patients in the Alpha group delivered when admitted to the intensive care unit, while less than half of those in the Delta group delivered when admitted; the rest were released home and continued their pregnancy normally. There was a significant difference regarding the number of patients released to home care and the number of days after admission when delivery occurred (p = 0.02 and 0.022, respectively). Conclusions: There was no significant difference in maternal and fetal outcomes between the two groups, except for the number of patients released to home care and the number of days after admission when delivery occurred. There was no correlation between any Brixia scores (H, L, A, E) and any maternal or fetal outcomes in both groups. Full article

Urinary tract infections (UTIs) are among the most common infective disease in the adult population. UTI diagnosis is based essentially on the presence of lower urinary tract symptoms (e.g., dysuria, urgency, and frequency) and the evidence of bacteriuria (by dipstick testing and/or urine culture). UTI diagnosis is not always easy because symptoms can be vague, or patient basal conditions can interfere negatively with the diagnostic process, whereas urine culture is still ongoing. In those cases, the differential diagnosis among UTIs and asymptomatic bacteriuria (ABU) may be challenging, while the clinician has to decide whether to start an antibiotic treatment shortly. The purpose of the present review is to analyze the biomarkers that could help in UTI diagnosis. Some biomarkers, such as procalcitonin, interleukin-6, neutrophil gelatinase-associated lipocalin, chemokines, lactoferrin, and bone morphogenetic protein-2, seem promising in UTI diagnosis, while other biomarkers failed to show any utility. Whereas a single biomarker was not enough, a combination of biomarkers could have more chances to help in the diagnosis. Full article

Diabetic retinopathy (DR) remains a prevalent complication of diabetes and a major cause of vision loss among the working population. Selective loss of pericytes and vascular smooth muscle cells (SMCs), the mural cells of the retinal blood vessels, is pathognomonic of the vasodegenerative element of diabetic retinopathy, and recent studies suggest a central role for autophagy-dependent cell death in this pathology. Our first study of archival electron micrographs from diabetic donor retina provided evidence for the involvement of autophagy in mural cell death during DR and the current report extends those observations to the fate of mural cell corpses in the vascular wall. Here we show that the efferocytosis, or phagocytic removal of dying mural cells, is carried out by a population of juxtavascular microglia (JVM). This population of microglia are well-characterised in the brain but previously unreported in the retina. We demonstrate that JVM are distinct from perivascular macrophages as they participate in the glia limitans of the retinal vasculature and constitute an integral component of the neurovascular unit of the retina. Importantly, mural cells undergoing active phagocytic engulfment appeared to represent relatively early stages in autophagy-dependent cell death, suggesting that the more degraded pericyte and SMC corpses, known as “ghosts”, have evaded efficient efferocytosis and undergone secondary necrosis. The alternative fates of mural cell corpses in the retinal vasculature may have important implications for inflammatory processes in the vasodegenerative pathology characteristic of DR. Full article

Diabetic retinopathy (DR) is the most common complication of diabetes and a major cause of vision loss worldwide. The premature death of the microvascular mural cells represents both a pathological hallmark of vasodegeneration in DR and a basis for therapeutic intervention to halt progression to the sight-threatening stages. Recent studies suggest that retinal microvascular mural cells, classed as pericytes in the capillaries and vascular smooth muscle cells in the larger vessels (VSMC), may undergo autophagy-dependent cell death during DR. The present investigation was undertaken to assess electron microscopic evidence for involvement of autophagy in mediation of cell death in the mural cells of the retinal vasculature, in eyes from human diabetic donors and diabetic dogs. All specimens examined showed widespread evidence of autophagosomes in processes of viable pericytes and VSMCs, and the membranous remnants of excessive autophagic activity in their “ghost cell” remnants within the vascular walls. Autophagy was termed “excessive” when it occupied the greater part of the cytoplasm in mural cell processes. This was notable in specimens from short-term diabetic donors with no evidence of basement-membrane thickening or mural cell loss, in which regions of mural cell cytoplasm filled with autophagic bodies appeared to be undergoing cytoplasmic cleavage. No equivalent evidence of autophagy was detected in the adjacent endothelial cells of the retinal vessels. We conclude that increased autophagy in the retinal pericytes and VSMCs is linked to the diabetic milieu, and over time may also act as a trigger for mural cell loss and progressive vasodegeneration. Full article

During the COVID-19 pandemic, lung ultrasound has been revealed as a powerful technique for diagnosis and follow-up of pneumonia, the principal complication of SARS-CoV-2 infection. Nevertheless, being a relatively new and unknown technique, the lack of trained personnel has limited its application worldwide. Computer-aided diagnosis could possibly help to reduce the learning curve for less experienced physicians, and to extend such a new technique such as lung ultrasound more quickly. This work presents the preliminary results of the ULTRACOV (Ultrasound in Coronavirus disease) study, aimed to explore the feasibility of a real-time image processing algorithm for automatic calculation of the lung ultrasound score (LUS). A total of 28 patients positive on COVID-19 were recruited and scanned in 12 thorax zones following the lung score protocol, saving a 3 s video at each probe position. Those videos were evaluated by an experienced physician and by a custom developed automated detection algorithm, looking for A-Lines, B-Lines, consolidations, and pleural effusions. The agreement between the findings of the expert and the algorithm was 88.0% for B-Lines, 93.4% for consolidations and 99.7% for pleural effusion detection, and 72.8% for the individual video score. The standard deviation of the patient lung score difference between the expert and the algorithm was ±2.2 points over 36. The exam average time with the ULTRACOV prototype was 5.3 min, while with a conventional scanner was 12.6 min. Conclusion: A good agreement between the algorithm output and an experienced physician was observed, which is a first step on the feasibility of developing a real-time aided-diagnosis lung ultrasound equipment. Additionally, the examination time was reduced to less than half with regard to a conventional ultrasound exam. Acquiring a complete lung ultrasound exam within a few minutes is possible using fairly simple ultrasound machines that are enhanced with artificial intelligence, such as the one we propose. This step is critical to democratize the use of lung ultrasound in these difficult times. Full article

Diabetes mellitus is a chronic disease often accompanied by diabetic retinopathy (DR), one of the most common diabetic complications. DR is an eye condition that causes vision deficiency and often leads to blindness. DR develops when blood vessels damage the retina, the light-sensitive tissue at the back of the eye. Before changes in retinal blood vessel permeability, different molecular and anatomical modifications take place in the retina, including early neural changes. This review will summarize the current status of knowledge regarding pathophysiological mechanisms underlying DR, with a special focus on early neural modifications associated with DR. We describe hyperglycemia-associated molecular and cellular alterations linked to the initiation and progression of DR. We also discuss retinal neurodegeneration as a shared feature in different in vitro and in vivo models of DR. Given how ubiquitous diabetes is and how severe the effects of DR are, we also examine the current pharmacological and genetic approaches for combatting this disease. Full article