IgA Nephropathy Associated with IgA Vasculitis Coexisting with Focal Segmental Glomerulosclerosis Tip Variant: A Case Report

IgA vasculitis (IgAV), previously known as Henoch–Schönlein purpura, is a form of small vessel vasculitis that affects the skin, joints, intestines, and kidneys. The clinical presentation in adults is usually infrequent, more severe, with a worse prognosis and a higher recurrence rate. Due to limited scientific evidence, IgAV is viewed similarly to IgA nephropathy (IgAN), and the renal histopathological lesions are indistinguishable between the two. IgAN is the most prevalent glomerular diseases worldwide. The diagnosis of IgAN is confirmed through a renal biopsy. The most frequently found histopathological lesions are mesangial proliferation and concurrent IgA deposition confirmed by direct immunofluorescence. Focal segmental glomerulosclerosis (FSGS) appears as a glomerular pattern of injury in up to 40% of renal biopsies with IgAN, although there are few reported cases in the international literature where both diseases coexist as primary etiologies. We report a case of a female patient presenting with vasculitic lesions, abdominal pain, and nephrotic syndrome, whose cause is confirmed by a renal biopsy with a diagnosis of IgAN secondary to IgAV and coexistence of FSGS, an unusual presentation with few case reports

Characterization of retinal drusen in subjects at high genetic risk of developing sporadic Alzheimer’s disease: An exploratory analysis

Having a family history (FH+) of Alzheimer’s disease (AD) and being a carrier of at least one ε4 allele of the ApoE gene are two of the main risk factors for the development of AD. AD and age-related macular degeneration (AMD) share one of the main risk factors, such as age, and characteristics including the presence of deposits (Aβ plaques in AD and drusen in AMD); however, the role of apolipoprotein E isoforms in both pathologies is controversial. We analyzed and characterized retinal drusen by optical coherence tomography (OCT) in subjects, classifying them by their AD FH (FH-or FH+) and their allelic characterization of ApoE ε4 (ApoE ε4-or ApoE ε4+) and considering cardiovascular risk factors (hypercholesterolemia, hypertension, and diabetes mellitus). In addition, we analyzed the choroidal thickness by OCT and the area of the foveal avascular zone with OCTA. We did not find a relationship between a family history of AD or any of the ApoE isoforms and the presence or absence of drusen. Subjects with drusen show choroidal thinning compared to patients without drusen, and thinning could trigger changes in choroidal perfusion that may give rise to the deposits that generate drusen

Production and characterisation of recombinant forms of human pulmonary surfactant protein C (SP-C): Structure and surface activity

Surfactant protein C (SP-C) is an essential component for the surface tension-lowering activity of the pulmonary surfactant system. It contains a valine-rich α helix that spans the lipid bilayer, and is one of the most hydrophobic proteins known so far. SP-C is also an essential component of various surfactant preparations of animal origin currently used to treat neonatal respiratory distress syndrome (NRDS) in preterm infants. The limited supply of this material and the risk of transmission of infectious agents and immunological reactions have prompted the development of synthetic SP-C-derived peptides or recombinant humanized SP-C for inclusion in new preparations for therapeutic use. We describe herein the recombinant production in bacterial cultures of SP-C variants containing phenylalanines instead of the palmitoylated cysteines of the native protein, as fusions to the hydrophilic nuclease A (SN) from Staphylococcus aureus. The resulting chimerae were partially purified by affinity chromatography and subsequently subjected to protease digestion. The SP-C forms were recovered from the digestion mixtures by organic extraction and further purified by size exclusion chromatography. The two recombinant SP-C variants so obtained retained more than 50% α-helical content and showed surface activity comparable to the native protein, as measured by surface spreading of lipid/protein suspensions and from compression π-A isotherms of lipid/protein films. Compared to the protein purified from porcine lungs, the recombinant SP-C forms improved movement of phospholipid molecules into the interface (during adsorption), or out from the interfacial film (during compression), suggesting new possibilities to develop improved therapeutic preparations

Adenda

PublishedEl Semillero de Investigación en Filosofía Colombiana y Latinoamericana, Ficla, es un espacio que reflexiona en torno a las ideas y a los pensadores de nuestra América. Aunque no se detiene estrictamente en la filosofía, trasciende a otros espacios, la literatura, la música, las artes, y, como queremos destacar en este libro, en la poesía. Ella está en movimiento, diría Paz, o es un “temblor panamericano”, diríamos bajo la custodia de Benedetti; es el trasegar de las letras más nobles que tiene nuestro terruño. Por “noble” no se debe entender un acto de buena fe, la mala fe (sartriana) juega un rol importante; es así que la revelación dada en estas letras rebela al más desinteresado lector

Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed

BACKGROUND: We studied whether thymidylate synthase (TS) genotype has an independent prognostic/predictive impact on a European population of advanced non-small cell lung cancer (NSCLC) patients receiving pemetrexed. METHODS: Twenty-five patients treated with pemetrexed-based regimens were included. Genomic DNA was isolated prior to treatment. The variable number of tandem repeat (VNTR) polymorphisms, the G > C single nucleotide polymorphisms (SNP) and the TS 6-bp insertion/deletion (6/6) in the 3' untranslated region (UTR) polymorphisms were analyzed and correlated with overall response rate (ORR), progression-free survival (PFS), overall-survival (OS) and toxicity. RESULTS: The genotype +6/+6 predicted a higher ORR among active/former smokers compared to +6/-6 genotype (100% vs. 50%; p = 0.085). Overall, the 3R/3R genotype predicted a higher ORR (100%) over the rest VNTR polymorphisms (p = 0.055). The presence of 3R/3R genotype significantly correlated with a superior ORR in patients without EGFR activating mutations (100%) compared to 2R/2R, 2R/3R and 3R/4R genotype (77.8%, 33.3% and 0% respectively; p = 0.017). After a median follow-up of 21 months, a trend towards a better PFS, although not significant, was found among subjects showing 3R/3R polymorphisms (p = 0.089). A significantly superior OS was found in patients showing 3R/3R genotype rather than other VNTR polymorphisms (p = 0.019). No significant correlation with the toxicity was observed. CONCLUSION: In our series, 3R/3R polymorphism correlated with a superior OS. Also, this polymorphism, when associated to wild type EGFR, was related to a higher ORR to pemetrexed. Toxicity was not significantly correlated with a specific TS genotype

Open Access

Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexe

Characterization of Retinal Drusen in Subjects at High Genetic Risk of Developing Sporadic Alzheimer’s Disease: An Exploratory Analysis

Having a family history (FH+) of Alzheimer’s disease (AD) and being a carrier of at least one ɛ4 allele of the ApoE gene are two of the main risk factors for the development of AD. AD and age-related macular degeneration (AMD) share one of the main risk factors, such as age, and characteristics including the presence of deposits (Aβ plaques in AD and drusen in AMD); however, the role of apolipoprotein E isoforms in both pathologies is controversial. We analyzed and characterized retinal drusen by optical coherence tomography (OCT) in subjects, classifying them by their AD FH (FH- or FH+) and their allelic characterization of ApoE ɛ4 (ApoE ɛ4- or ApoE ɛ4+) and considering cardiovascular risk factors (hypercholesterolemia, hypertension, and diabetes mellitus). In addition, we analyzed the choroidal thickness by OCT and the area of the foveal avascular zone with OCTA. We did not find a relationship between a family history of AD or any of the ApoE isoforms and the presence or absence of drusen. Subjects with drusen show choroidal thinning compared to patients without drusen, and thinning could trigger changes in choroidal perfusion that may give rise to the deposits that generate druse

Effects of IFIH1 rs1990760 variants on systemic inflammation and outcome in critically ill COVID-19 patients in an observational translational study

Variants in IFIH1, a gene coding the cytoplasmatic RNA sensor MDA5, regulate the response to viral infections. We hypothesized that IFIH1 rs199076 variants would modulate host response and outcome after severe COVID-19. Patients admitted to an intensive care unit (ICU) with confirmed COVID-19 were prospectively studied and rs1990760 variants determined. Peripheral blood gene expression, cell populations, and immune mediators were measured. Peripheral blood mononuclear cells from healthy volunteers were exposed to an MDA5 agonist and dexamethasone ex-vivo, and changes in gene expression assessed. ICU discharge and hospital death were modeled using rs1990760 variants and dexamethasone as factors in this cohort and in-silico clinical trials. About 227 patients were studied. Patients with the IFIH1 rs1990760 TT variant showed a lower expression of inflammation-related pathways, an anti-inflammatory cell profile, and lower concentrations of pro-inflammatory mediators. Cells with TT variant exposed to an MDA5 agonist showed an increase in IL6 expression after dexamethasone treatment. All patients with the TT variant not treated with steroids survived their ICU stay (hazard ratio [HR]: 2.49, 95% confidence interval [CI]: 1.29-4.79). Patients with a TT variant treated with dexamethasone showed an increased hospital mortality (HR: 2.19, 95% CI: 1.01-4.87) and serum IL-6. In-silico clinical trials supported these findings. COVID-19 patients with the IFIH1 rs1990760 TT variant show an attenuated inflammatory response and better outcomes. Dexamethasone may reverse this anti-inflammatory phenotype. Centro de Investigación Biomédica en Red (CB17/06/00021), Instituto de Salud Carlos III (PI19/00184 and PI20/01360), and Fundació La Marató de TV3 (413/C/2021). Patients with severe COVID-19 often need mechanical ventilation to help them breathe and other types of intensive care. The outcome for many of these patients depends on how their immune system reacts to the infection. If the inflammatory response triggered by the immune system is too strong, this can cause further harm to the patient. One gene that plays an important role in inflammation is IFIH1 which encodes a protein that helps the body to recognize viruses. There are multiple versions of this gene which each produce a slightly different protein. It is possible that this variation impacts how the immune system responds to the virus that causes COVID-19. To investigate, Amado-Rodríguez, Salgado del Riego et al. analyzed the IFIH1 gene in 227 patients admitted to an intensive care unit in Spain for severe COVID-19 between March and December 2020. They found that patients with a specific version of the gene called TT experienced less inflammation and were more likely to survive the infection. Physicians typically treat patients with moderate to severe COVID-19 with corticosteroid drugs that reduce the inflammatory response. However, Amado-Rodríguez, Salgado del Riego et al. found that patients with the TT version of the IFIH1 gene were at greater risk of dying if they received corticosteroids. The team then applied the distribution of IFIH1 variants among different ethnic ancestries to data from a previous clinical trial, and simulated the effects of corticosteroid treatment. This 'mock' clinical trial supported their findings from the patient-derived data, which were also validated by laboratory experiments on immune cells from individuals with the TT gene. The work by Amado-Rodríguez, Salgado del Riego et al. suggests that while corticosteroids benefit some patients, they may cause harm to others. However, a real-world clinical trial is needed to determine whether patients with the TT version of the IFIH1 gene would do better without steroids

Divulgación Científica No. 5

En los países iberoamericanos, así como en otras regiones del mundo, existe una discusión permanente sobre el deterioro el medioambiente. Las instituciones de educación superior contamos con una vasta producción bibliográfica que queremos compartir con todos los interesados y con la sociedad. Por esa razón, la Asociación de Editoriales Universitarias de América Latina y el Caribe (Eulac)* dando continuidad a nuestro proyecto de editoriales universitarias Enlazadas, presentamos este año la propuesta Enlazadas por el medioambiente, que abordará esta inquietud desde diversos ejes en el marco de las ferias del libro más importantes del mundo.In Ibero-American countries, as well as in other regions of the world, there is a permanent discussion about the deterioration of the environment. Higher education institutions have a vast bibliographic production that we want to share with all interested parties and with society. For this reason, the Association of University Presses of Latin America and the Caribbean (Eulac)*, giving continuity to our project of Enlazadas university presses, we present this year the proposal Enlazadas for the environment, which will address this concern from various axes within the framework of the most important book fairs in the world

Todos muy capaces

El trabajo obtuvo un Premio Tomás García Verdejo a las buenas prácticas educativas en la Comunidad Autónoma de Extremadura para el curso académico 2015/2016. Modalidad BSe describe un proyecto llevado a cabo con alumnos de 4º de diversificación y 2º de Formación Profesional Básica del IES Bioclimático de Badajoz, que consistió en realizar diversas actividades con la asociación Aspaceba (Asociación de Parálisis Cerebral de Badajoz) y que tuvo como objetivos principales que los alumnos se informase sobre la discapacidad en general y sobre la parálisis cerebral en particular, que se acercaran al mundo de la discapacidad superarando las barreras físicas y psicológicas, que conociesen los aspectos positivos y las necesidades de apoyo y recursos de las personas con discapacidad, que trabajasen la empatía y el respeto como mecanismo para entender sentimientos y vivencias de los demás y que rechazaran situciones de injusticia hacia personas con alguna discapacidadAndalucíaES