Policies and gender in Argentina: contributions from anthropology and feminism

Las políticas públicas, herramienta de poder indispensable para el ejercicio de gobierno de la población, definen “problemas” y “poblaciones” como objetos de intervención. Tales políticas se presentan como producto de un conocimiento experto y técnico que, por lo mismo, se coloca por encima y por fuera de la sociedad, que lo asume neutral, objetivo. Desde allí, el colectivo “mujeres” aparece en la agenda de políticas públicas, al tiempo que la academia se hace eco de ella. Centrándose en los estudios etnográficos volcados a las políticas y la vida cotidiana, los estudios culturales, los estudios post-coloniales y el feminismo crítico, este artículo analiza los aportes de la antropología para abordar las diversas formas y sentidos de las actuales políticas públicas, con la intención de (re)conocer los modos en que ellas organizan, producen y reproducen lo que se entiende por femenino y masculino. Simultáneamente, interesa desnaturalizar la construcción de subjetividades homogéneas –generizadas y sexuadas– atendiendo a las diversas modalidades de acción, demandas y resistencias a través de las cuales los sujetos se definen y redefinen a sí mismos, y que los revela transformadores de las políticas.Public policies are an indispensable tool for the exercise of power through government of population. These policies define both "problems" and "populations" as objects of intervention. They are stated as a product of a technical expertise, placed above and outside society, and, therefore, assumed as neutral and objective. This same logic enables the group "women" on the public policies agenda, generating various responses from the academic realm. Taking into account ethnographic studies focused on policies and everyday life, cultural studies, post-colonial studies and critical feminism, this article analyzes the contributions of anthropology to address the various forms and meanings of existing policies. By this it is intended to (re)cognize the ways in which these policies organize, produce and reproduce what is meant by female and male. As well as de-naturalizing the construction of homogeneous subjectivities - gendered and sexed- by focusing on the various modes of action, demands and resistance through which individuals define and redefine themselves, and which reveal them as transforming these same policies.Fil: del Rio Fortuna, Cynthia Anahi. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gonzalez Martin, Miranda. Universidad de Buenos Aires; ArgentinaFil: Pais Andrade, Marcela Alejandra. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Recurrent Focal Segmental Glomerulosclerosis in Renal Allograft Recipients: Role of Human Leukocyte Antigen Mismatching and Other Clinical Variables

Recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation impacts long-term graft survival and limits access to transplantation. We hypothesized that HLA donor/recipient matching could be used as a surrogate marker of recurrence. In a retrospective study of 42 pediatric and 77 adult subjects with primary FSGS, transplanted from 1990 to 2007 at a single center, we analyzed the degree of donor/recipient HLA compatibility and other clinical variables associated with FSGS recurrence. There were total of 131 allografts for primary FSGS (11 subjects were transplanted twice, and 1 had a third allograft) with 20 cases of FSGS recurrence (17 children) in the primary allograft, and two children who had FSGS recurrence in the second allograft. Fifty-two subjects (40%) were African American, and 66 (50%) Caucasians. Recurrent FSGS and controls were not different for age at transplant, gender, donor source, acute/chronic rejection episodes, and HLA matches. Recurrent FSGS was not associated with HLA mismatches; power equals 83%. Immunosuppressive regimen had no effect on recurrence of FSGS, P = .75. Recurrent FSGS is not associated with HLA mismatching, acute cellular or vascular rejection, and occurs primarily in the pediatric population

Hypertension, Chronic Kidney Disease, and Renal Pathology in a Child with Hermansky-Pudlak Syndrome

We report a child with Hermansky-Pudlak Syndrome (HPS) and chronic kidney disease (stage II) with histological diagnosis of focal segmental glomerulosclerosis (FSGS). A 15-year-old male of Puerto Rico ancestry with history of HPS, hypertension (HTN), asthma, obesity, and chronic kidney disease (CKD) stage II presented with new-onset proteinuria without edema. His blood pressure had been controlled, serum creatinine had been 0.9–1.4 mg/dL, and first morning urine protein/creatinine ratio (UPC) ranged from 0.2 to 0.38. Due to persistent nonorthostatic proteinuria with CKD, renal biopsy was performed and FSGS (not otherwise specified) with chronic diffuse tubulopathy (tubular cytoplasmic droplets) and acute tubular injury was reported. Ceroid-like material is known to infiltrate tissues (i.e., lungs, colon, and kidney) in HPS, but the reason for the renal insufficiency is unknown. Nonspecific kidney disease and in one adult case IgA nephropathy with ANCA-positive glomerulonephritis have previously been reported in patients with Hermansky-Pudlak syndrome. To our knowledge, we report the first pediatric renal pathology case of HPS associated with CKD. This paper discusses presentation and management of renal disease in HPS

Effects of photodynamic therapy on dermal fibroblasts from xeroderma pigmentosum and Gorlin-Goltz syndrome patients

PDT is widely applied for the treatment of non-melanoma skin cancer premalignant and malignant lesions (actinic keratosis, basal cell carcinoma and in situ squamous cell carcinoma). In photodynamic therapy (PDT) the interaction of a photosensitizer (PS), light and oxygen leads to the formation of reactive oxygen species (ROS) and thus the selective tumor cells eradication. Xeroderma pigmentosum (XP) and Gorlin-Goltz Syndrome (GS) patients are at high risk of developing skin cancer in sun-exposed areas. Therefore, the use of PDT as a preventive treatment may constitute a very promising therapeutic modality for these syndromes. Given the demonstrated role of cancer associated fibroblasts (CAFs) in tumor progression and the putative CAFs features of some cancer-prone genodermatoses fibroblasts, in this study, we have further characterized the phenotype of XP and GS dermal fibroblasts and evaluated their response to methyl-d-aminolevulinic acid (MAL)-PDT compared to that of dermal fibroblasts obtained from healthy donors. We show here that XP/GS fibroblasts display clear features of CAFs and present a significantly higher response to PDT, even after being stimulated with UV light, underscoring the value of this therapeutic approach for these rare skin conditions and likely to other forms of skin cancer were CAFs play a major role.FL and AJ were supported, respectively, by grants PI14/00931 and PI15/00974, from Instituto de Salud Carlos III, MINECO and Feder Funds and by S2010/ BMD-2359 from Comunidad de Madrid. MDR was supported by grant S2010/BMD-2420 from Comunidad de Madrid and SAF2013-43475-R from MINECO. AZ was supported by S2010/BMD-2359 from Comunidad de Madrid

811. Correction of Laminin-5 β3 Chain Deficiency in Human Epidermal Stem Cells by Transcriptionally Targeted Lentiviral Vectors

Mutations in any of the genes encoding the laminin 5 heterotrimer (|[alpha]|3, |[beta]|3 and |[gamma]|2) cause junctional epidermolysis bullosa (JEB), a severe and often fatal skin adhesion defect. We and others have shown that expression of a retrovirally transferred |[beta]|3-chain cDNA in keratinocytes from affected patients reconstitutes normal synthesis, assembly and secretion of laminin 5, and corrects the adhesion defect in vitro and in vivo. We have recently started a phase-I clinical trial of gene therapy of JEB based on transplantation of cultured skin derived from autologous epidermal stem cells transduced with a MLV-derived retroviral vector. Since gamma- retroviral vectors have raised safety concerns for the genotoxic risk associated with the insertion of LTR elements into the human genome, we developed an alternative gene transfer strategy based on LTR- modified, HIV-derived lentiviral vectors. Two self-inactivating (SIN) lentiviral vectors were built, in which expression of either GFP or a LAMB3 cDNA is under the control of either a constitutive promoter (PGK) or the keratinocyte-specific, 2.2-kb promoter-enhancer of keratin 14 (K14). In a third construct, expression of the transgene is under the control of the viral LTR, modified by replacing the U3 region with two K14 enhancer elements. Analysis in human keratinocyte cultures and in full-thickness human skin equivalents reconstituted onto immunodeficient mice showed that GFP expression directed by the K14 elements is tissue-specific and restricted to the basal layer of the epidermis. Expression of laminin5 from the three alternative vectors was evaluated in keratinocyte cultures derived from skin biopsies of JEB patients. Biochemical and cell kinetics assays demonstrated transduction of epidermal clonogenic stem/progenitor cells and full phenotypic correction of JEB keratinocytes with all vectors. Southern blot analysis of individual cell clones showed that LTR-modified lentiviral vectors are genetically stable and integrate in multiple copies in the human genome. This study shows that the use of lentiviral vectors transcriptionally targeted to the basal keratinocytes by the insertion of restricted enhancer elements is an effective, and potentially safer, alternative for gene therapy of JEB

Oxidative stress and mitochondrial dysfunction in Kindler syndrome

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: Kindler Syndrome (KS) is an autosomal recessive skin disorder characterized by skin blistering, photosensitivity, premature aging, and propensity to skin cancer. In spite of the knowledge underlying cause of this disease involving mutations of FERMT1 (fermitin family member 1), and efforts to characterize genotype-phenotype correlations, the clinical variability of this genodermatosis is still poorly understood. In addition, several pathognomonic features of KS, not related to skin fragility such as aging, inflammation and cancer predisposition have been strongly associated with oxidative stress. Alterations of the cellular redox status have not been previously studied in KS. Here we explored the role of oxidative stress in the pathogenesis of this rare cutaneous disease. [Methods]: Patient-derived keratinocytes and their respective controls were cultured and classified according to their different mutations by PCR and western blot, the oxidative stress biomarkers were analyzed by spectrophotometry and qPCR and additionally redox biosensors experiments were also performed. The mitochondrial structure and functionality were analyzed by confocal microscopy and electron microscopy.[Results]: Patient-derived keratinocytes showed altered levels of several oxidative stress biomarkers including MDA (malondialdehyde), GSSG/GSH ratio (oxidized and reduced glutathione) and GCL (gamma-glutamyl cysteine ligase) subunits. Electron microscopy analysis of both, KS skin biopsies and keratinocytes showed marked morphological mitochondrial abnormalities. Consistently, confocal microscopy studies of mitochondrial fluorescent probes confirmed the mitochondrial derangement. Imbalance of oxidative stress biomarkers together with abnormalities in the mitochondrial network and function are consistent with a pro-oxidant state. [Conclusions]: This is the first study to describe mitochondrial dysfunction and oxidative stress involvement in KS.FL was supported by grants from Instituto de Salud Carlos III (PI11/01225) and Comunidad de Madrid (S2010/BMD- 2359; SKINMODEL). MDR was supported by grants from the Science and Innovation Ministry of Spain SAF2010-16976), Comunidad de Madrid (S2010/BMD-2420; CELLCAM), GENEGRAFT - contract N° HEALTH-F2-2011-261392 and CIBERER ACCI 13-714/172.04. MG is supported in part by ERA-NET grant: E-Rare-2 (SpliceEB). EZ was in part supported by a fellowship from CIBERER and SAF2010-16976.Peer reviewe

Effects of the binding of a Helianthus annuus lectin to Candida albicans cell wall on biofilm development and adhesion to host cells

Background: In our previous study, we isolated and characterized a lectin called Helja from Helianthus annuus (sunflower) and then, in a further study, demonstrated its antifungal activity against Candida spp. Since Candida infections are a major health concern due to the increasing emergence of antifungal resistant strains, the search for new antifungal agents offers a promising opportunity for improving the treatment strategies against candidiasis. Purpose: The aim of this work was to get insights about the mechanism of action of Helja, an antifungal lectin of H. annuus, and to explore its ability to inhibit Candida albicans biofilm development and adherence to buccal epithelial cells (BEC). Study design/methods: Yeast viability was evaluated by Evans Blue uptake and counting of colony forming units (CFU). The yeast cell integrity was assessed using Calcofluor White (CFW) as a cell wall perturbing agent and sorbitol as osmotic protectant. The induction of oxidative stress was evaluated using 3,3′-diaminobenzidine (DAB) for detection of hydrogen peroxide. The adherence was determined by counting the yeast cells attached to BEC after methylene blue staining. The biofilms were developed on polystyrene microplates, visualized by confocal laser scanning microscopy and the viable biomass was quantified by CFU counting. The binding lectin-Candida was assessed using Helja conjugated to fluorescein isothiocyanate (Helja-FITC) and simultaneous staining with CFW. The cellular surface hydrophobicity (CSH) was determined using a microbial adhesion to hydrocarbons method. Results: C. albicans cells treated with 0.1 µg/µl of Helja showed a drastic decrease in yeast survival. The lectin affected the fungal cell integrity, induced the production of hydrogen peroxide and inhibited the morphological transition from yeast to filamentous forms. Helja caused a significant reduction of adherent cells and a decrease in biofilm biomass and coverage area. The treatment with the protein also reduced the surface hydrophobicity of fungal cells. We show the binding of Helja-FITC to yeast cells distributed as a thin outer layer to the CFW signal, and this interaction was displaced by mannose and Concanavalin A. Conclusion: The results demonstrate the interaction of Helja with the mannoproteins of C. albicans cell wall, the disruption of the cell integrity, the induction of oxidative stress, the inhibition of the morphological transition from yeast to filamentous forms and the fungal cell viability loss. The binding Helja-Candida also provides a possible explanation of the lectin effect on cell adherence, biofilm development and CSH, relevant features related to virulence of the pathogen.Fil: del Rio, Marianela Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: de la Canal, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Pinedo, Marcela Lilian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Mora Montes, Héctor M.. Universidad de Guanajuato; MéxicoFil: Regente, Mariana Clelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; Argentin

Assessment of the risk and characterization of non-melanoma skin cancer in Kindler syndrome: study of a series of 91 patients.

BACKGROUND: Kindler Syndrome (KS) is a rare genodermatosis characterized by skin fragility, skin atrophy, premature aging and poikiloderma. It is caused by mutations in the FERMT1 gene, which encodes kindlin-1, a protein involved in integrin signalling and the formation of focal adhesions. Several reports have shown the presence of non-melanoma skin cancers in KS patients but a systematic study evaluating the risk of these tumors at different ages and their potential outcome has not yet been published. We have here addressed this condition in a retrospective study of 91 adult KS patients, characterizing frequency, metastatic potential and body distribution of squamous cell carcinoma (SCC) in these patients. SCC developed in 13 of the 91 patients. RESULTS: The youngest case arose in a 29-year-old patient; however, the cumulative risk of SCC increased to 66.7% in patients over 60 years of age. The highly aggressive nature of SCCs in KS was confirmed showing that 53.8% of the patients bearing SCCs develop metastatic disease. Our data also showed there are no specific mutations that correlate directly with the development of SCC; however, the mutational distribution along the gene appears to be different in patients bearing SCC from SCC-free patients. The body distribution of the tumor appearance was also unique and different from other bullous diseases, being concentrated in the hands and around the oral cavity, which are areas of high inflammation in this disease. CONCLUSIONS: This study characterizes SCCs in the largest series of KS patients reported so far, showing the high frequency and aggressiveness of these tumors. It also describes their particular body distribution and their relationship with mutations in the FERMT-1 gene. These data reinforce the need for close monitoring of premalignant or malignant lesions in KS patients

Preemptive Use of Eculizumab for Living-Donor Kidney Transplantation in a Child with Atypical Hemolytic Uremic Syndrome

Eculizumab is an anti-complement C5 monoclonal antibody that has recently been reported as an effective therapy for atypical hemolytic uremic syndrome. However, few data are available on the preemptive use of this medication in pediatric kidney transplantation. This report describes a successful preemptive use of eculizumab in combination with living unrelated kidney transplanta- tion in a 10-year-old child with end-stage renal disease secondary to atypical hemolytic uremic syndrome who has a complement factor H mutation that has not been previously reported. Further observations and clinical trials are required to address the challenges and areas of uncertainty related to preemptive eculizumab therapy for kidney transplantation in children and adults with atypical hemolytic uremic syndrome.

Long-term Engraftment of Single Genetically Modified Human Epidermal Holoclones Enables Safety Pre-assessment of Cutaneous Gene Therapy

Predicting the risks of permanent gene therapy approaches involving the use of integrative gene-targeting vectors has become a critical issue after the unfortunate episode of a clinical trial in children with X-linked severe combined immunodeficiency (X-SCID). Safety pre-assessment of single isolated gene-targeted stem cells or their derivative clones able to regenerate their tissue of origin would be a major asset in addressing untoward gene therapy effects in advance. Human epidermal stem cells, which have extensive proliferative potential in vitro, theoretically offer such a possibility as a method of assessment. By means of optimized organotypic culture and grafting methods, we demonstrate the long-term in vivo regenerative capacity of single gene-targeted human epidermal stem cell clones (holoclones). Both histopathological analysis of holoclone-derived grafts in immunodeficient mice and retroviral insertion site mapping performed in the holoclone in vitro and after grafting provide proof of the feasibility of pre-assessing genotoxicity risks in isolated stem cells before transplantation into patients. Our results provide an experimental basis for previously untested assumptions about the in vivo behavior of epidermal stem cells prospectively isolated in vitro and pave the way for a safer approach to cutaneous gene therapy