Efficacy of the tissue regenerating agent (RGTA) in the treatment of neurotrophic corneal ulcers and persistent epithelial defects

Purpose : To report the results obtained in a series of 58 eyes with chronic corneal ulcers and persistent epithelial defects resistant to conventional therapy and treated with 0.01% poly-carboxymethylglucose sulfate (RGTA, Cacicol®). Methods : A prospective study was made of 58 eyes of patients with corneal ulcers and persistent epithelial lesions secondary to neurotrophic disorders, caustic damage, ulcerated metaherpetic lesions, Stevens-Johnson syndrome, peripheral ulcerative keratitis and severe dry eye, among other conditions. The ulcers were essentially chronic and slow-evolving, with mean vertical and horizontal diameters of 2.4 and 2.7 mm, respectively (range 1-5.5 mm). All patients had been previously treated with classical tear substitutes, and some had also received blood products, topical cyclosporine, corticosteroids, amniotic membrane coverings, therapeutic contact lenses and/or a vitamin-based eye ointment. The patients received an initial dose of one drop in the morning every 48 hours during 10 days. After evaluation of the effects of treatment, new dosing schemes were prescribed for those patients who had improved their clinical condition though without complete resolution of the disease. Results : Important variation was observed in the time to recovery of corneal integrity, ranging from a few days to some weeks, depending on the severity and etiology of the case. Full healing was recorded in 50 patients. The patients with large neurotrophic ulcers showed improvement of the lesions, with a decrease in lesion size after 15 days of treatment. Eight eyes did not achieve complete healing. In the case of severe ulceration and when a positive effect was observed after one month, treatment was continued with spacing of the applications until complete healing was achieved. All patients reported subjective improvement. The drug showed immediate efficacy in 11 eyes with epithelialisation disorders following PRK or trauma, with recovery of tissue integrity after the first treatment period. Conclusions : The tissue regenerating agent (RGTA, Cacicol®) is an interesting and effective topical adjuvant product for the treatment of severe and chronic corneal ulcers resistant to conventional treatment. Its efficacy remains to be confirmed in the context of double-blind, randomised clinical trials

The fossil vertebrates from Somosaguas (Pozuelo, Madrid, Spain)

[ES] Dos yacimientos de vertebrados, situados en el Campus de Somosaguas de la Universidad Complutense (Pozuelo de Alarcón, Madrid), han proporcionado unos 600 restos identificables en estados de conservación muy variados, pertenecientes a unas veinte especies de tamaños muy diversos, desde mastodontes a musarañas. Su estudio permite fechar su edad en unos 14 m.a. y reconstruir un periodo árido en la cuenca de Madrid, ocupada durante el Mioceno medio por bosques y sabanas subtropicales con fuertes avenidas y sin ríos permanentes. En estos yacimientos se puede realizar una enseñanza práctica de la Paleontología de Vertebrados, para formación de estudiantes universitarios en el estudio y la gestión del Patrimonio Paleontológico.[EN] Two vertebrate fossil sites, situated in the Universidad Complutense Campus of Somosaguas, (Pozuelo de Alarcón, Madrid, Spain) have yielded about 600 identifiable rests in different preservation states, belonging to about twenty species of highly diverse sizes, from mastodons to shrews. Their study allows dating at about 14 m.y., and reconstructing an arid climate epoch in the Madrid basin during middle Miocene times, occupied by subtropical woodlands and savannahs with strong floods and without permanent rivers. These fossil sites allow practical teaching of Vertebrate Palaeontology, and preparing university students in the Palaeontological Heritage study and management.Hemos recibido financiación y personal respaldo del Rectorado de la Universidad Complutense de Madrid, de los Decanatos de la Facultad de Ciencias Políticas y Sociología y de la Facultad de Ciencias Geológicas, y del Departamento de Paleontología de esta Facultad. El Departamento de Paleobiología del Museo Nacional de Ciencias Naturales (CSIC) realiza su investigación en el marco del Convenio de Colaboración con la Comunidad de Madrid a través de la Dirección General de Patrimonio Histórico Artístico de la Consejería de Educación.Peer reviewe

A randomized comparison ofrepeat stenting with balloon angioplasty in patients with in-stent restenosis

AbstractObjectivesThis randomized trial compared repeat stenting with balloon angioplasty (BA) in patients with in-stent restenosis (ISR).BackgroundStent restenosis constitutes a therapeutic challenge. Repeat coronary interventions are currently used in this setting, but the recurrence risk remains high.MethodsWe randomly assigned 450 patients with ISR to elective stent implantation (224 patients) or conventional BA (226 patients). Primary end point was recurrent restenosis rate at six months. Secondary end points included minimal lumen diameter (MLD), prespecified subgroup analyses, and a composite of major adverse events.ResultsProcedural success was similar in both groups, but in-hospital complications were more frequent in the balloon group. After the procedure MLD was larger in the stent group (2.77 ± 0.4 vs. 2.25 ± 0.5 mm, p < 0.001). At follow-up, MLD was larger after stenting when the in-lesion site was considered (1.69 ± 0.8 vs. 1.54 ± 0.7 mm, p = 0.046). However, the binary restenosis rate (38% stent group, 39% balloon group) was similar with the two strategies. One-year event-free survival (follow-up 100%) was also similar in both groups (77% stent vs. 71% balloon, p = 0.19). Nevertheless, in the prespecified subgroup of patients with large vessels (≥3 mm) the restenosis rate (27% vs. 49%, p = 0.007) and the event-free survival (84% vs. 62%, p = 0.002) were better after repeat stenting.ConclusionsIn patients with ISR, repeat coronary stenting provided better initial angiographic results but failed to improve restenosis rate and clinical outcome when compared with BA. However, in patients with large vessels coronary stenting improved the long-term clinical and angiographic outcome

Unique genomic profile of fibrolamellar hepatocellular carcinoma

BACKGROUND & AIMS: Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary hepatic cancer that develops in children and young adults without cirrhosis. Little is known about its pathogenesis, and it can be treated only with surgery. We performed an integrative genomic analysis of a large series of patients with FLC to identify associated genetic factors. METHODS: By using 78 clinically annotated FLC samples, we performed whole-transcriptome (n = 58), single-nucleotide polymorphism array (n = 41), and next-generation sequencing (n = 48) analyses; we also assessed the prevalence of the DNAJB1-PRKACA fusion transcript associated with this cancer (n = 73). We performed class discovery using non-negative matrix factorization, and functional annotation using gene-set enrichment analyses, nearest template prediction, ingenuity pathway analyses, and immunohistochemistry. The genomic identification of significant targets in a cancer algorithm was used to identify chromosomal aberrations, MuTect and VarScan2 were used to identify somatic mutations, and the random survival forest was used to determine patient prognoses. Findings were validated in an independent cohort. RESULTS: Unsupervised gene expression clustering showed 3 robust molecular classes of tumors: the proliferation class (51% of samples) had altered expression of genes that regulate proliferation and mammalian target of rapamycin signaling activation; the inflammation class (26% of samples) had altered expression of genes that regulate inflammation and cytokine enriched production; and the unannotated class (23% of samples) had a gene expression signature that was not associated previously with liver tumors. Expression of genes that regulate neuroendocrine function, as well as histologic markers of cholangiocytes and hepatocytes, were detected in all 3 classes. FLCs had few copy number variations; the most frequent were focal amplification at 8q24.3 (in 12.5% of samples), and deletions at 19p13 (in 28% of samples) and 22q13.32 (in 25% of samples). The DNAJB1-PRKACA fusion transcript was detected in 79% of samples. FLC samples also contained mutations in cancer-related genes such as BRCA2 (in 4.2% of samples), which are uncommon in liver neoplasms. However, FLCs did not contain mutations most commonly detected in liver cancers. We identified an 8-gene signature that predicted survival of patients with FLC. CONCLUSIONS: In a genomic analysis of 78 FLC samples, we identified 3 classes based on gene expression profiles. FLCs contain mutations and chromosomal aberrations not previously associated with liver cancer, and almost 80% contain the DNAJB1-PRKACA fusion transcript. By using this information, we identified a gene signature that is associated with patient survival time

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

Efecto de la luz y la sequía sobre la anatomía foliar de plantas de alcornoque ("Quercus suber" L.)

Se estudió el efecto conjunto de la disponibilidad de luz y agua, a lo largo de dos ciclos de sequía, sobre la estructura y anatomía foliares en plantas de alcornoque (Quercus suber L.) cultivadas en vivero. Los brinzales se mantuvieron bajo la combinación de cuatro niveles de luz y dos contenidos hídricos en el suelo, con los tratamientos replicados en tres bloques. La densidad de flujo fotosintético (PPFD) bajo cada régimen lumínico fue T68: 66-70% , T50: 44-50%, T15: 13.5-16% y T5: 5-6%, respecto a pleno sol. La mitad de las plantas se regaron a capacidad de campo dos veces por semana (R+: 25-35% de humedad, medido con TDR), y la otra mitad se sometió a dos ciclos de sequía de 51 y 38 días, respectivamente (R-: sin riego, hasta alcanzar una humedad entre 7 y 10% al final del primer ciclo). Se observó una clara influencia de la luz sobre la estructura foliar, con una disminución significativa del área foliar específica (SLA) y un aumento del grosor de la lámina foliar (GL) con el progresivo incremento en los niveles relativos de PPFD. La disminución de SLA estuvo determinada por un mayor desarrollo del parénquima en empalizada (PE) y lagunar (PL), si bien éste aumentó en menor medida que el primero; lo que quedó confirmado por una relación negativa entre la densidad de la lámina y el SLA. El efecto del riego no fue estadísticamente significativo. En cuanto a la epidermis del haz y el envés, no se observó ningún patrón claro debido a las disponibilidades de luz o agua. Se discuten las posibles implicaciones ecológicas en los patrones anatómicos y estructurales foliares observados

Identification of quantitative trait loci and candidate genes for primary metabolite content in strawberry fruit

Selective breeding: The genetic basis of better strawberries Investigations have yielded early insights into the genetic basis of strawberry taste and nutrition. Such information informs efforts to selectively breed the fruit to maximize these qualities. A team of researchers from Spain and Germany, led by the University of Malaga’s Sonia Osorio and the IFAPA´s Iraida Amaya, found 133 locations within strawberry DNA that correlated to variation in metabolic pathways and desirable traits including acidity, sugar content, and the concentration of l-ascorbic acid (vitamin C). Only a small number of associations persisted over the 2 years of investigations, suggesting that environmental factors also wield a significant influence over the strawberry fruit’s molecular makeup. The team then used their data to identify a series of candidate genes that may be functionally linked to strawberry qualities; however, further research is needed to validate those connections

ARMCX3 Mediates Susceptibility to Hepatic Tumorigenesis Promoted by Dietary Lipotoxicity

Lipotoxicitat; ObesitatLipotoxicity; ObesityLipotoxicidad; ObesidadARMCX3 is encoded by a member of the Armcx gene family and is known to be involved in nervous system development and function. We found that ARMCX3 is markedly upregulated in mouse liver in response to high lipid availability, and that hepatic ARMCX3 is upregulated in patients with NAFLD and hepatocellular carcinoma (HCC). Mice were subjected to ARMCX3 invalidation (inducible ARMCX3 knockout) and then exposed to a high-fat diet and diethylnitrosamine-induced hepatocarcinogenesis. The effects of experimental ARMCX3 knockdown or overexpression in HCC cell lines were also analyzed. ARMCX3 invalidation protected mice against high-fat-diet-induced NAFLD and chemically induced hepatocarcinogenesis. ARMCX3 invalidation promoted apoptotic cell death and macrophage infiltration in livers of diethylnitrosamine-treated mice maintained on a high-fat diet. ARMCX3 downregulation reduced the viability, clonality and migration of HCC cell lines, whereas ARMCX3 overexpression caused the reciprocal effects. SOX9 was found to mediate the effects of ARMCX3 in hepatic cells, with the SOX9 interaction required for the effects of ARMCX3 on hepatic cell proliferation. In conclusion, ARMCX3 is identified as a novel molecular actor in liver physiopathology and carcinogenesis. ARMCX3 downregulation appears to protect against hepatocarcinogenesis, especially under conditions of high dietary lipid-mediated hepatic insult.The study was supported by grant 201337-30-31-32 Fundació la Marató de TV3, grant SAF2017-85722R (Ministerio de Economia y Competitividad) to F.V., grant PID2019-106764RB-C21/ AEI/ 10.13039/501100011033 from the Spanish Ministry of Science and a collaborative grant from CIBERNED to E.S, grant PI18/00961 (Instituto de Salud Carlos III) to B.M, and the Hepacare Project grant from Fundación La Caixa to M.A.A. and C.B. F.V. and E.S. are ICREA researchers