101 research outputs found
La integración social como desafío: análisis del programa de campamentos en Chile (2011-2018)
One of the main challenges for social integration in Latin American cities is the presence of informal settlements, where a significant percentage of the poorest urban population live. Although in Chile urban informality is less frequent than in other countries of the region, the recent growth of informal settlements bestows greater relevance to the problem. This article studies the effects on social integration and exclusion of policies aimed at informal settlements in Chile, specifically through the execution of the Programa de Campamentos or ‘informal settlements’ program’ between 2011 and 2018. Analysis considers quantitative data from Informal Settlements’ Surveys, and the study of four cases in different regions in the country focusing on strategies aimed at informal settlement closure strategies through a qualitative analysis of interviews, focus groups and walking tours. The results reveal the importance of dimensions such as affect and attachment, sense of belonging and participation in the generation of social integration, thus allowing for the discussion of perspectives on integration that are based exclusively on spatial proximity.Uno de los principales desafíos para la integración social en las ciudades latinoamericanas es la presencia de asentamientos informales, que alojan a un porcentaje importante de la población urbana empobrecida. Si bien en Chile la informalidad urbana es menos frecuente que en otros países de la región, el reciente crecimiento de los campamentos le otorga una mayor relevancia al problema. En este contexto, el presente artículo estudia los efectos de integración social y exclusión de las políticas dirigidas a asentamientos informales en Chile, específicamente a través del Programa de Campamentos y su ejecución entre 2011 y 2018. Para ello, se analizan los resultados de catastros de campamentos y se realiza un estudio de cuatro casos de estrategias de cierre de campamentos en diferentes regiones del país, a través de un análisis de entrevistas, grupos focales y recorridos colectivos. Los resultados relevan la importancia de incorporar dimensiones como el afecto y apego, el sentido de pertenencia y la participación en la generación de integración social, lo que permite discutir las perspectivas sobre la integración que se basan exclusivamente en la cercanía espacial
Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomes
Endotips; Glomerulosclerosi segmentària focal; Resposta inflamatòriaEndotipos; Glomeruloesclerosis segmentaria focal; Respuesta inflamatoriaEndotypes; Focal segmental glomerulosclerosis; Inflammatory responseObjectives
Idiopathic focal segmental glomerulosclerosis (FSGS) has been linked to immunological and inflammatory response dysregulations. The aim of this study was to find endotypes of FSGS patients using a cluster (CL) analysis based on inflammatory and immunological variables, and to analyse whether a certain endotype is associated with response to treatment with corticosteroids.
Methods
This prospective observational study included patients with idiopathic FSGS diagnosed by kidney biopsy. Serum levels of soluble interleukin (IL)-1 receptor, tumoural necrosis factor alpha, Interferon gamma (IFNγ), IL-6, IL-17, IL-12, IL-23, IL-13, IL-4, IL-5, IL-6, haemopexin (Hx), haptoglobin (Hgl), soluble urokinase-type plasminogen activator receptor (suPAR) and urinary CD80 (uCD80) were measured with enzyme-linked immunosorbent assay or nephelometry. T-helper lymphocyte populations and T-regulatory lymphocytes were analysed by flow cytometry. A factorial analysis followed by a k-means CL analysis was performed.
Results
A total of 79 FSGS patients were included. Three CLs were identified. CL1 (27.8%) included IL-12, IL-17, IL-23 and a T helper 17 (Th17) pattern. CL2 (20.2%) included IL-4, IL-5, IL-13, immunoglobulin E and Th2 pattern. CL3 (51.8%) included IL-6, Hx, Hgl, suPAR and uCD80. There were no differences in age, gender, kidney function, albumin or proteinuria among CLs. About 42/79 patients (53.1%) showed cortico-resistance. The prevalence of cortico-resistance was significantly lower in CL2 (4/16, 25%) than in CL1 (16/26, 72.7%) and CL3 (22/41, 53.7%) (P = 0.018), with no significant differences between CLs 1 and 3 (P = 0.14).
Conclusions
Patients with FSGS and indistinguishable clinical presentation at diagnosis were classified in three distinct CLs according to predominant Th17, Th2 and acute inflammatory responses that display differences in clinical response to treatment with corticosteroids
Activation of the acute inflammatory phase response in idiopathic nephrotic syndrome: association with clinicopathological phenotypes and with response to corticosteroids
Glomeruloesclerosis; Inflamación; Síndrome nefróticoGlomerulosclerosis; Inflammation; Nephrotic syndromeGlomeruloesclerosi; Inflamació; Síndrome nefròticaBackground
Data on the activation of the acute inflammatory response and its clinicopathological associations in idiopathic nephrotic syndrome (INS) are scarce and discordant.
Objective
To analyse the associations between the activation of the inflammatory response, the clinicopathological characteristics of disease and the response to treatment with steroids in patients with INS.
Methods
A total of 101 patients with INS due to minimal change disease (MCD; n = 44), focal segmental glomerulosclerosis (FSGS; n = 33) and membranous nephropathy (MN; n = 24) and 50 healthy controls were included. At diagnosis, we measured the levels of haemopexin (Hx), haptoglobin (Hgl), interleukin-6 (IL-6), soluble urokinase-type plasminogen activator receptor (suPAR), tumour necrosis factor-α (TNF-α), soluble IL-1 receptor, interferon-γ and C-reactive protein. We analysed their clinicopathological associations. In MCD and FSGS patients, we determined the association between the levels of these variables and steroid resistance.
Results
The levels of Hx, Hgl, TNF-α, suPAR and IL-6 were higher in patients with INS than in healthy controls, and were not associated with proteinuria, estimated glomerular filtration rate or serum albumin. In MCD and FSGS patients, Hx, Hgl, IL-6 and TNF-α levels were similar and significantly higher than in MN patients. In patients with MCD and FSGS, multivariate analyses identified FSGS and the levels of Hx, Hgl or IL-6 as independent predictors of steroid resistance.
Conclusions
The activation of the inflammatory response in patients with INS is heterogeneous and more prevalent in MCD or FSGS patients than in those with MN. In MCD and FSGS, elevated levels of Hx, Hgl or IL-6 are independently associated with steroid resistance
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Interleukin-15 and interferon-gamma participate in the cross-talk between natural killer and monocytic cells required for tumour necrosis factor production.
RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.We have characterized the lymphocyte subset and the receptor molecules involved in inducing the secretion of TNF by monocytic cells in vitro. The TNF secreted by monocytic cells was measured when they were co-cultured with either resting or IL-15-stimulated lymphocytes, T cells, B cells or natural killer (NK) cells isolated from the peripheral blood of healthy subjects and from the synovial fluid from patients with inflammatory arthropathies. Co-culture with IL-15-activated peripheral blood or synovial fluid lymphocytes induced TNF production by monocytic cells within 24 hours, an effect that was mainly mediated by NK cells. In turn, monocytic cells induced CD69 expression and IFN-gamma production in NK cells, an effect that was mediated mainly by beta2 integrins and membrane-bound IL-15. Furthermore, IFN-gamma increased the production of membrane-bound IL-15 in monocytic cells. Blockade of beta2 integrins and membrane-bound IL-15 inhibited TNF production, whereas TNF synthesis increased in the presence of anti-CD48 and anti-CD244 (2B4) monoclonal antibodies. All these findings suggest that the cross-talk between NK cells and monocytes results in the sustained stimulation of TNF production. This phenomenon might be important in the pathogenesis of conditions such as rheumatoid arthritis in which the synthesis of TNF is enhanced
Poor phenotype-genotype association in a large series of patients with Type III Bartter syndrome
Excreció; Genètica humana; MutacióExcreción; Genética humana; MutaciónExcretion; Human genetics; MutationIntroduction
Type III Bartter syndrome (BS) is an autosomal recessive renal tubule disorder caused by loss-of-function mutations in the CLCNKB gene, which encodes the chloride channel protein ClC-Kb. In this study, we carried out a complete clinical and genetic characterization in a cohort of 30 patients, one of the largest series described. By comparing with other published populations, and considering that 80% of our patients presented the p.Ala204Thr Spanish founder mutation presumably associated with a common phenotype, we aimed to test the hypothesis that allelic differences could explain the wide phenotypic variability observed in patients with type III BS.
Methods
Clinical data were retrieved from the referral centers. The exon regions and flanking intronic sequences of the CLCNKB gene were screened for mutations by polymerase chain reaction (PCR) followed by direct Sanger sequencing. Presence of gross deletions or duplications in the region was checked for by MLPA and QMPSF analyses.
Results
Polyuria, polydipsia and dehydration were the main common symptoms. Metabolic alkalosis and hypokalemia of renal origin were detected in all patients at diagnosis. Calciuria levels were variable: hypercalciuria was detected in 31% of patients, while 23% had hypocalciuria. Nephrocalcinosis was diagnosed in 20% of the cohort. Two novel CLCNKB mutations were identified: a small homozygous deletion (c.753delG) in one patient and a small deletion (c.1026delC) in another. The latter was present in compound heterozygosis with the already previously described p.Glu442Gly mutation. No phenotypic association was obtained regarding the genotype.
Conclusion
A poor correlation was found between a specific type of mutation in the CLCNKB gene and type III BS phenotype. Importantly, two CLCNKB mutations not previously described were found in our cohortThis study was supported by two grants (PI09/90888 and PI11/01412) from the FIS of the Instituto de Salud Carlos III, Madrid, Spain, the Department of Health of the Basque Government (2014111064), and the Department of Education of the Basque Government (IT795-13)
CD44-negative parietal–epithelial cell staining in minimal change disease: association with clinical features, response to corticosteroids and kidney outcome
Idiopathic nephrotic syndrome; Minimal change disease; Parietal–epithelial cellsSíndrome nefrótico idiopático; Enfermedad de cambios mínimos; Células parietales-epitelialesSíndrome nefròtica idiopàtica; Malaltia de canvis mínims; Cèl·lules parietals-epitelialsBackground
Activation of parietal–epithelial cells (PECs) with neo-expression of CD44 has been found to play a relevant role in the development of focal and segmental glomerulosclerosis (FSGS). The aim of this study was to analyse whether the expression of CD44 by PECs in biopsies of minimal change disease (MCD) is associated with the response to corticosteroids, with kidney outcomes and/or can be considered an early sign of FSGS.
Methods
This multicentric, retrospective study included paediatric and adult patients with MCD. Demographic, clinical and biochemical data were recorded, and biopsies were stained with anti-CD44 antibodies. The association between PECs, CD44 expression and the response to corticosteroids, and kidney outcomes were analysed using logistic, Kaplan–Meier and Cox regression analyses.
Results
A total of 54 patients were included: 35 (65%) <18 years and 19 (35%) adults. Mean follow-up was 68.3 ± 37.9 months. A total of 19/54 patients (35.2%) showed CD44-positive staining. CD44-positive patients were younger (14.5 ± 5 versus 21.5 ± 13, P = 0.006), and showed a higher incidence of steroid-resistance [11/19 (57.8%) versus 7/35 (20%), P = 0.021; odds ratio: 5.5 (95% confidence interval 1.6–18), P = 0.007] and chronic kidney disease [9/19 (47.3%) versus 6/35 (17.1%), P = 0.021; relative risk: 3.01 (95% confidence interval 1.07–8.5), P = 0.037]. Follow-up re-biopsies of native kidneys (n = 18), identified FSGS lesions in 10/12 (83.3%) of first-biopsy CD44-positive patients versus 1/6 (16.7%) of first-biopsy CD44-negative patients (P = 0.026).
Conclusions
In patients with a light microscopy pattern of MCD, CD44-positive staining of PECs is associated with a higher prevalence of steroid resistance and worse kidney outcomes, and can be considered an early sign of FSGS.C.M. is supported by a Miguel Servet grant, Fondo de investigación sanitaria, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovacio´n y Universidades [CP18/00116]. No additional funding was required for the current study
Multimodal texts for the strengthening of Emotional Intelligence
La inteligencia emocional es la capacidad del ser humano
de controlar sus emociones, y de esta manera
mejorar las relaciones interpersonales y son éstas
las que juegan un papel fundamental en la vida del
ser humano. La presente investigación tiene como
objetivo general fortalecer la inteligencia emocional
por medio de textos multimodales en la IED Janeiro
en el departamento del Magdalena. El estudio se llevó
a cabo desde la mirada cualitativa, empleando la
entrevista estructurada como técnica de recolección
de información. Los actores participantes fueron los
estudiantes del grado noveno con la participación de
(30) en la investigación. Como conclusiones se puede
resaltar que los participantes se motivan a aprender
y participan en el manejo y control de emociones
presentes al momento de entrar en contacto con los
procesos de enseñanza-aprendizaje.Emotional intelligence is the ability of the human
being to control their emotions, and in this way
improve intra and interpersonal relationships and
these are the ones that play a fundamental role in
the life of the human being. The general objective
of this research is to strengthen emotional intelligence
through multimodal texts in IED Janeiro
in the department of Magdalena. The study was
carried out from the qualitative perspective, using
the structured interview as a technique for
gathering information. The participating actors
were ninth grade students with the participation
of (30) in the research. As conclusions, it can be
highlighted that participants are motivated to
learn and participate in the management and
control of present emotions when they come into
contact with the teaching-learning processes
Genetics of Type III Bartter Syndrome in Spain, Proposed Diagnostic Algorithm
9 p.The p.Ala204Thr mutation (exon 7) of the CLCNKB gene is a "founder" mutation that causes most of type III Bartter syndrome cases in Spain. We performed genetic analysis of the CLCNKB gene, which encodes for the chloride channel protein ClC-Kb, in a cohort of 26 affected patients from 23 families. The diagnostic algorithm was: first, detection of the p.Ala204Thr mutation; second, detecting large deletions or duplications by Multiplex Ligation-dependent Probe Amplification and Quantitative Multiplex PCR of Short Fluorescent Fragments; and third, sequencing of the coding and flanking regions of the whole CLCNKB gene. In our genetic diagnosis, 20 families presented with the p.Ala204Thr mutation. Of those, 15 patients (15 families) were homozygous (57.7% of overall patients). Another 8 patients (5 families) were compound heterozygous for the founder mutation together with a second one. Thus, 3 patients (2 siblings) presented with the c. -19-?_2053+? del deletion (comprising the entire gene); one patient carried the p.Val170Met mutation (exon 6); and 4 patients (3 siblings) presented with the novel p.Glu442Gly mutation (exon 14). On the other hand, another two patients carried two novel mutations in compound heterozygosis: one presented the p.Ile398_Thr401del mutation (exon 12) associated with the c. -19-?_2053+? del deletion, and the other one carried the c.1756+1G>A splice-site mutation (exon 16) as well as the already described p.Ala210Val change (exon 7). One case turned out to be negative in our genetic screening. In addition, 51 relatives were found to be heterozygous carriers of the described CLCNKB mutations. In conclusion, different mutations cause type III Bartter syndrome in Spain. The high prevalence of the p.Ala204Thr in Spanish families thus justifies an initial screen for this mutation. However, should it not be detected further investigation of the CLCNKB gene is warranted in clinically diagnosed families.This study was supported by two grants (PI09/90888 and PI11/01412) from the FIS of the Instituto de Salud Carlos III, Madrid, Spain, and the Eitb Maratoia-Bioef (BIO08/ER/020) the Basque Foundation for Health Innovation and Research (BIOEF, from the Basque Berrikuntza + Ikerketa + Osasuna Eusko Fundazioa). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses.
Natural killer (NK) cells recognize and kill target cells undergoing different types of stress. NK cells are also capable of modulating immune responses. In particular, they regulate T cell functions. Small RNA next-generation sequencing of resting and activated human NK cells and their secreted extracellular vesicles (EVs) led to the identification of a specific repertoire of NK-EV-associated microRNAs and their post-transcriptional modifications signature. Several microRNAs of NK-EVs, namely miR-10b-5p, miR-92a-3p, and miR-155-5p, specifically target molecules involved in Th1 responses. NK-EVs promote the downregulation of GATA3 mRNA in CD4+ T cells and subsequent TBX21 de-repression that leads to Th1 polarization and IFN-γ and IL-2 production. NK-EVs also have an effect on monocyte and moDCs (monocyte-derived dendritic cells) function, driving their activation and increased presentation and costimulatory functions. Nanoparticle-delivered NK-EV microRNAs partially recapitulate NK-EV effects in mice. Our results provide new insights on the immunomodulatory roles of NK-EVs that may help to improve their use as immunotherapeutic tools.This manuscript was funded by grants PDI-2020-120412RB-I00 and PDC2021- 121719-I00 (FS-M) and PID2020-
119352RB-I00 (AS) from the Spanish Ministry of Economy and Competitiveness; CAM (S2017/BMD3671-INFLAMUNE-CM) from the Comunidad de Madrid (FS-M). CIBERCV (CB16/11/00272) and
BIOIMID PIE13/041 from the Instituto de Salud Carlos. The current research has received funding
from 'la Caixa' Foundation under the project code HR17-00016. Grants from Ramón Areces Foundation 'Ciencias de la Vida y de la Salud' (XIX Concurso-2018) and from Ayuda Fundación BBVA y Equipo
de Investigación Científica (BIOMEDICINA-2018) (to FSM). The CNIC is supported by the Ministerio
de Ciencia, Innovacion y Universidades and the Pro-CNIC Foundation, and is a Severo Ochoa Center
of Excellence (SEV-2015–0505). IMDEA Nanociencia acknowledges support from the ‘Severo Ochoa’
Programme for Centres of Excellence in R&D (MINECO, CEX2020-001039-S). SGD is supported by
a grant from the Spanish Ministry of Universities. Authors thank Dr Miguel Vicente-Manzanares for
critical review and editing. We also thank Dr Francisco Urbano and Dr Covadonga Aguado for their
support with EM (TEM facilities, Universidad Autónoma de Madrid).S
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