Consenso colombiano de atención, diagnóstico y manejo de la infección por SARS-COV-2/COVID-19 en establecimientos de atención de la salud Recomendaciones basadas en consenso de expertos e informadas en la evidencia

The “Asociación Colombiana de Infectología” (ACIN) and the “Instituto de Evaluación de Nuevas Tecnologías de la Salud” (IETS) created a task force to develop recommendations for Covid 19 health care diagnosis, management and treatment informed, and based, on evidence. Theses reccomendations are addressed to the health personnel on the Colombian context of health services. © 2020 Asociacion Colombiana de Infectologia. All rights reserved

Colombian consensus recommendations for diagnosis, management and treatment of the infection by SARS-COV-2/ COVID-19 in health care facilities - Recommendations from expert´s group based and informed on evidence

La Asociación Colombiana de Infectología (ACIN) y el Instituto de Evaluación de Nuevas Tecnologías de la Salud (IETS) conformó un grupo de trabajo para desarrollar recomendaciones informadas y basadas en evidencia, por consenso de expertos para la atención, diagnóstico y manejo de casos de Covid 19. Estas guías son dirigidas al personal de salud y buscar dar recomendaciones en los ámbitos de la atención en salud de los casos de Covid-19, en el contexto nacional de Colombia

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95%

MSC transplantation: a promising therapeutic strategy to manage the onset and progression of diabetic nephropathy

Currently, one of the main threats to public health is diabetes mellitus. Its most detrimental complication is diabetic nephropathy (DN), a clinical syndrome associated with kidney damage and an increased risk of cardiovascular disease. Irrespective of the type of diabetes, DN follows a well-known temporal course. The earliest detectable signs are microalbuminuria and histopathological changes including extracellular matrix deposition, glomerular basement membrane thickening, glomerular and mesangial expansion. Later on macroalbuminuria appears, followed by a progressive decline in glomerular filtration rate and the loss of glomerular podocytes, tubulointerstitial fibrosis, glomerulosclerosis and arteriolar hyalinosis. Tight glycemic and hypertension controls remain the key factors for preventing or arresting the progression of DN. Nevertheless, despite considerable educational effort to control the disease, a significant number of patients not only develop DN, but also progress to chronic kidney disease. Therefore, the availability of a strategy aimed to prevent, delay or revert DN would be highly desirable. In this article, we review the pathophysiological features of DN and the therapeutic mechanisms of multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs). The perfect match between them, together with encouraging pre-clinical data available, allow us to support the notion that MSC transplantation is a promising therapeutic strategy to manage DN onset and progression, not only because of the safety of this procedure, but mainly because of the renoprotective potential of MSCs

A Tetrameric Peptide Derived from Bovine Lactoferricin Exhibits Specific Cytotoxic Effects against Oral Squamous-Cell Carcinoma Cell Lines

Several short linear peptides derived from cyclic bovine lactoferricin were synthesized and tested for their cytotoxic effect against the oral cavity squamous-cell carcinoma (OSCC) cell lines CAL27 and SCC15. As a control, an immortalized and nontumorigenic cell line, Het-1A, was used. Linear peptides based on the RRWQWR core sequence showed a moderate cytotoxic effect and specificity towards tumorigenic cells. A tetrameric peptide, LfcinB(20–25)4, containing the RRWQWR motif, exhibited greater cytotoxic activity (>90%) in both OSCC cell lines compared to the linear lactoferricin peptide or the lactoferrin protein. Additionally, this tetrameric peptide showed the highest specificity towards tumorigenic cells among the tested peptides. Interestingly, this effect was very fast, with cell shrinkage, severe damage to cell membrane permeability, and lysis within one hour of treatment. Our results are consistent with a necrotic effect rather than an apoptotic one and suggest that this tetrameric peptide could be considered as a new candidate for the therapeutic treatment of OSCC

The role of bone marrow mesenchymal stromal cell derivatives in skin wound healing in diabetic mice

<div><p>Mesenchymal stromal cells (MSCs) have shown to be a promising tool in cell therapies to treat different conditions. Several pre-clinical and clinical studies have proved that the transplantation of MSCs improves wound healing. Here, we compare the beneficial effects of mouse bone marrow-derived allogeneic MSCs (allo-mBM-MSCs) and their acelullar derivatives (allo-acd-mMSCs) on skin wound healing in Non-Obese Diabetic (NOD) mice. One dose of allo-mBM-MSCs (1×10⁶ cells) or one dose of allo-acd-mMSCs (1X) were intradermally injected around wounds in 8–10 week old female NOD mice. Wound healing was evaluated macroscopically (wound closure) every two days, and microscopically (reepithelialization, dermoepidermal junction, skin appendage regeneration, leukocyte infiltration, vascularization, granulation tissue formation, and density of collagen fibers in the dermis) after 16 days of MSC injection. In addition, we measured growth factors and specific proteins that were present in the allo-acd-mMSCs. Results showed significant differences in the wound healing kinetics of lesions that received allo-acd-mMSCs compared to lesions that received vehicle or allo-mBM-MSCs. In particular, mice treated with allo-acd-mMSCs reached significantly higher percentages of wound closure at day 4, 6 and 8, relative to the allo-mBM-MSCs and vehicle groups (p < 0.05), while wound closure percentages could not be statistically distinguished between the allo-mBM-MSCs and vehicle groups. Also, allo-acd-mMSCs had a greater influence in the skin would healing process. Specifically, they caused a less pronounced inflammatory severe response (p < 0.0001), more granulation tissue formation at an advanced stage (p < 0.0001), and higher density of collagen fibers (p < 0.05) compared to the other groups. Nevertheless, at day 16, both allo-mBM-MSCs and allo-acd-mMSCs revealed a higher effect on the recovery of the quality skin (continuous epidermis; regular dermoepidermal junction and skin appendages) relative to untreated lesions (p < 0.0001), but not between them. On the other hand, ELISA analyses indicated that the allo-acd-mMSCs contained growth factors and proteins relevant to wound healing such as IGF-1, KGF, HGF, VEGF, ANG-2, MMP-1, CoL-1 and PGE2. Compared to allo-acd-mMSCs, the administration of allo-mBM-MSCs is insufficient for wound healing in diabetic mice and delays the therapeutic effect, which maybe explained by the fact that trophic factors secreted by MSCs are critical for skin regeneration, and not the cells per se, suggesting that MSCs may require some time to secrete these factors after their administration.</p></div

Suicide HSVtk Gene Delivery by Neurotensin-Polyplex Nanoparticles via the Bloodstream and GCV Treatment Specifically Inhibit the Growth of Human MDA-MB-231 Triple Negative Breast Cancer Tumors Xenografted in Athymic Mice

<div><p>The human breast adenocarcinoma cell line MDA-MB-231 has the triple-negative breast cancer (TNBC) phenotype, which is an aggressive subtype with no specific treatment. MDA-MB-231 cells express neurotensin receptor type 1 (NTSR1), which makes these cells an attractive target of therapeutic genes that are delivered by the neurotensin (NTS)-polyplex nanocarrier via the bloodstream. We addressed the relevance of this strategy for TNBC treatment using NTS-polyplex nanoparticles harboring the herpes simplex virus thymidine kinase (HSVtk) suicide gene and its complementary prodrug ganciclovir (GCV). The reporter gene encoding green fluorescent protein (GFP) was used as a control. NTS-polyplex successfully transfected both genes in cultured MDA-MB-231 cells. The transfection was demonstrated pharmacologically to be dependent on activation of NTSR1. The expression of HSVtk gene decreased cell viability by 49% (<i>P</i><0.0001) and induced apoptosis in cultured MDA-MB-231 cells after complementary GCV treatment. In the MDA-MB-231 xenograft model, NTS-polyplex nanoparticles carrying either the HSVtk gene or GFP gene were injected into the tumors or via the bloodstream. Both routes of administration allowed the NTS-polyplex nanoparticles to reach and transfect tumorous cells. HSVtk expression and GCV led to apoptosis, as shown by the presence of cleaved caspase-3 and Apostain immunoreactivity, and significantly inhibited the tumor growth (55–60%) (<i>P</i><0.001). At the end of the experiment, the weight of tumors transfected with the HSVtk gene was 55% less than that of control tumors (<i>P</i><0.05). The intravenous transfection did not induce apoptosis in peripheral organs. Our results offer a promising gene therapy for TNBC using the NTS-polyplex nanocarrier.</p></div

Histological analysis of dermo-epidermal junction and appendage-like structure formation of skin wounds 16 days after treatment with allo-mBM-MSCs and allo-acd-mMSCs in NOD mice.

<p>(A) Wound histological representative images of haematoxylin-eosin staining showing dermo-epidermal junction, which are indicated by arrows. Scale bar = 100 <i>μ</i>m. (B) Frequency of animals with the histological scores for dermo-epidermal junction. The score was assigned based on the junction level and was quantified using ImageJ (scores: IV: 0.1–400 pixels (complete junction), III: 401–750 pixels, II: 751–1,200 pixels, I: 1,201–2,800 pixels and 0: > 2,801 (incomplete junction). (C) Representative images of Masson’s trichrome staining illustrating appendage-like structure in the dermis indicated by arrows. Scale bar = 50 <i>μ</i>m. (D) Frequency of animals with the score for appendage-like structure. (n = 25, 25 and 27 for vehicle, allo-mBM-MSCs and allo-acd-mMSCs groups, respectively). Analysis of Pearson’s chi-square test was used, * indicates a significant difference (p < 0.0001). Abbreviations: NOD, Non-Obese Diabetic; allo-mBM-MSCs, mouse bone marrow-derived allogeneic MSCs; allo-acd-mMSCs and mouse bone marrow acelullar derivatives allogeneic MSCs.</p

Histological analysis of leucocyte infiltration, granulation tissue and collagen fibers of skin wounds 16 days after treatment with allo-mBM-MSCs and allo-acd-mMSCs in NOD mice.

<p>Frequency of animals with the histological scores for: <b>(A)</b> leukocyte infiltration in the dermis, (<b>B</b>) granulation tissue formation stage and (<b>C</b>) quantitative analysis of the intensity of dermal collagen fibers. (n = 25, 25 and 27 for vehicle, allo-mBM-MSCs and allo-acd-mMSCs groups, respectively). Pearson’s chi-square test and variance (ANOVA) analysis were used, * indicates a significant difference p < 0.0001 and ** p < 0.05. Abbreviations: NOD, Non-Obese Diabetic; allo-mBM-MSCs, mouse bone marrow-derived allogeneic MSCs and allo-acd-mMSCs, mouse bone marrow acelullar derivatives allogeneic MSCs.</p

Effects of allo-mBM-MSCs or allo-acd-mMSCs on wound closure in murine excisional wounds.

<p>(<b>A)</b> Representative images of the wounds in NOD mice under vehicle, allo-mBM-MSCs or allo-acd-mMSCs treatments at day 0 (before treatment), 4, 8, 10, 12 and 16 for NOD wounds. (<b>B)</b> Wound closure analysis. All wounds were measured using digital calipers at day 0, 2, 4, 6, 8, 10, 12 and 16 post-operation. The wound closure rate is plotted as the reduction percentage of original wound area over time (n = 25, 25 and 27 for vehicle, allo-mBM-MSCs and allo-acd-mMSCs groups, respectively). Analysis of variance (ANOVA) was used, * indicates a significant difference (p < 0.05). Abbreviations: NOD, Non-Obese Diabetic; allo-mBM-MSCs, mouse bone marrow-derived allogeneic MSCs and allo-acd-mMSCs, mouse bone marrow acelullar derivatives allogeneic MSCs.</p