Applicability of bioengineered human skin: from preclinical skin humanized mouse models to clinical regenerative therapies

Ongoing progress in the field of regenerative medicine, in combination with the development of tissue-engineered skin products, has opened new possibilities for the treatment of certain diseases in which current treatments are aimed at alleviating symptoms but are not able to get a permanent cure. Our laboratory has developed a fibrin-based bioengineered human skin that has been successfully used for permanent regenerative therapies in different situations in the clinic. Moreover, we have been able to stably regenerate human skin by orthotopic grafting of this skin equivalent onto the back of immunodeficient mice. The so-called skin-humanized mouse model system has permitted us to model several monogenic skin diseases, when keratinocytes and fibroblasts harboring the genetic defect were used. In most cases different gene therapy approaches for ex vivo correction of cells have proved effective in reverting the phenotype using this model. More importantly, the feasibility of the system has allowed us to generate a skin humanized mouse model for psoriasis, a common chronic inflammatory disease where the immune component has a pivotal role in the pathogenesis. Establishing reliable humanized animal models for skin diseases is necessary to gain a deeper knowledge of the pathogenesis and to develop novel therapeutic strategies. In this sense, the skin humanized mouse model developed in our laboratory meets the needs of this field of research.This work was supported by grant SAF 2010-16976

El cambio climático y las condiciones ambientales en los partidos de La Plata, Berisso y Ensenada, provincia de Buenos Aires: aspectos preliminares

Se presentan las tareas iniciales realizadas en relación al proyecto Efectos del cambio climático en las condiciones ambientales de los Partidos de Berisso, Ensenada y La Plata, que es financiado por la Universidad Nacional de La Plata en el marco del programa de “Proyectos de innovación y transferencia en áreas prioritarias (PIT-AP). Con este proyecto, iniciado en 2011, se propone avanzar en el conocimiento y evaluación de la influencia que generan los cambios climáticos en las condiciones ambientales del borde sur del Río de La Plata. Estos cambios pueden producir importantes efectos en el desarrollo socioeconómico y en los riesgos a que se encuentra sometida esta región. Debido a la escasez de datos básicos y la falta de un conocimiento adecuado de las condiciones ambientales de la región, se están realizando los estudios geológicos, geomorfológicos, hidrológicos, ecológicos y topográficos necesarios para el modelado de posibles escenarios de los cambios climáticos

SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome

El cambio climático y las condiciones ambientales en los partidos de La Plata, Berisso y Ensenada, provincia de Buenos Aires: aspectos preliminares

Se presentan las tareas iniciales realizadas en relación al proyecto Efectos del cambio climático en las condiciones ambientales de los Partidos de Berisso, Ensenada y La Plata, que es financiado por la Universidad Nacional de La Plata en el marco del programa de “Proyectos de innovación y transferencia en áreas prioritarias (PIT-AP). Con este proyecto, iniciado en 2011, se propone avanzar en el conocimiento y evaluación de la influencia que generan los cambios climáticos en las condiciones ambientales del borde sur del Río de La Plata. Estos cambios pueden producir importantes efectos en el desarrollo socioeconómico y en los riesgos a que se encuentra sometida esta región. Debido a la escasez de datos básicos y la falta de un conocimiento adecuado de las condiciones ambientales de la región, se están realizando los estudios geológicos, geomorfológicos, hidrológicos, ecológicos y topográficos necesarios para el modelado de posibles escenarios de los cambios climáticos.Facultad de Ciencias Naturales y Muse

El cambio climático y las condiciones ambientales en los partidos de La Plata, Berisso y Ensenada, provincia de Buenos Aires: aspectos preliminares

Se presentan las tareas iniciales realizadas en relación al proyecto Efectos del cambio climático en las condiciones ambientales de los Partidos de Berisso, Ensenada y La Plata, que es financiado por la Universidad Nacional de La Plata en el marco del programa de “Proyectos de innovación y transferencia en áreas prioritarias (PIT-AP). Con este proyecto, iniciado en 2011, se propone avanzar en el conocimiento y evaluación de la influencia que generan los cambios climáticos en las condiciones ambientales del borde sur del Río de La Plata. Estos cambios pueden producir importantes efectos en el desarrollo socioeconómico y en los riesgos a que se encuentra sometida esta región. Debido a la escasez de datos básicos y la falta de un conocimiento adecuado de las condiciones ambientales de la región, se están realizando los estudios geológicos, geomorfológicos, hidrológicos, ecológicos y topográficos necesarios para el modelado de posibles escenarios de los cambios climáticos.Facultad de Ciencias Naturales y Muse

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Targeted silencing of DEFB4 in a bioengineered skin-humanized mouse model for psoriasis: development of siRNA SECosome-based novel therapies

Psoriasis is a complex inflammatory skin disease that presents a wide variety of clinical manifestations. Human β defensin-2 (hBD-2) is highly up-regulated in psoriatic lesions and has been defined as a biomarker for disease activity. We explored the potential benefits of targeting hBD-2 by topical application of DEFB4-siRNA-containing SECosomes in a bioengineered skin-humanized mouse model for psoriasis. A significant improvement in the psoriatic phenotype was observed by histological examination, with a normalization of the skin architecture and a reduction in the number and size of blood vessels in the dermal compartment. Treatment leads to the recovery of transglutaminase activity, filaggrin expression and stratum corneum appearance to the levels similar to those found in normal regenerated human skin. The availability of a reliable skin-humanized mouse model for psoriasis in conjunction with the use of the SECosome technology may provide a valuable preclinical tool for identifying potential therapeutic targets for this disease

<i>OPA1</i> Dominant Optic Atrophy: Diagnostic Approach in the Pediatric Population

A clinical and genetic study was conducted with pediatric patients and their relatives with optic atrophy 1 (OPA1) mutations to establish whether there is a genotype–phenotype correlation among the variants detected within and between families. Eleven children with a confirmed OPA1 mutation were identified during the study period. The main initial complaint was reduced visual acuity (VA), present in eight patients of the cohort. Eight of eleven patients had a positive family history of optic atrophy. The mean visual acuity at the start of the study was 0.40 and 0.44 LogMAR in the right and left eye, respectively. At the end of the study, the mean visual acuity was unchanged. Optical coherence tomography during the first visit showed a mean retinal nerve fiber layer thickness of 81.6 microns and 80.5 microns in the right and left eye, respectively; a mean ganglion cell layer of 52.5 and 52.4 microns, respectively, and a mean central macular thickness of 229.5 and 233.5 microns, respectively. The most common visual field defect was a centrocecal scotoma, and nine out of eleven patients showed bilateral temporal disc pallor at baseline. Sequencing of OPA1 showed seven different mutations in the eleven patients, one of which, NM_130837.3: c.1406_1407del (p.Thr469LysfsTer16), has not been previously reported. Early diagnosis of dominant optic atrophy is crucial, both for avoiding unnecessary consultations and/or treatments and for appropriate genetic counseling