Association of SOD1 gene variants (50 bp Ins/Del, rs4817415, rs2070424, rs1041740, rs17880135) with plasma protein levels in vitiligo patients and their analysis in silico.

OBJECTIVE: Vitiligo is a common systemic, idiopathic autoimmune disease. The aim of this study was to analyze the frequency of variants of the superoxide dismutase 1 (SOD1) gene (50 bp Ins/Del, rs4817415, rs2070424, rs1041740, rs17880135) and circulating plasma protein levels through in-silico analysis. PATIENTS AND METHODS: Blood samples were collected from adult patients of both sexes with a clinical diagnosis of vitiligo. ELISA tests for SOD and analysis of gene variants by qPCR were compared to a disease-free reference group. RESULTS: The population analyzed was young people between 29 and 37 years old, with a higher percentage of women. The population was found in the Hardy-Weinberg equilibrium (HWE). The 50 bp Ins/Del, rs4817415, and rs2070424 variants showed no significant difference between groups (p > 0.05). Although, in the dominant model, the CT and CTTT genotypes of the rs1041740 and rs17880135 variants showed an association with susceptibility to vitiligo compared to the control. Plasma SOD levels showed significant differences between the groups, and when stratified according to the genotypes of each variant, there was a significant difference, except with the rs17880135 variant. The haplotypes InsCGTC and InsAGCC are shown to be risk factors for susceptibility to vitiligo. The in-silico analysis demonstrated that the rs4817415, rs2070424, rs1041740, and rs17880135 variants of the SOD1 gene participate in the modification of selected regulatory elements for differentiating the protein, transcription factors, and long non-coding RNA. CONCLUSIONS: Information regarding the pathogenesis of vitiligo helps recognize risk factors and identify the relationship of diagnostic markers of cell damage inherent to the disease. This will help improve aspects of prevention and the choice of treatment alternatives appropriate to each case.

Feasibility of Using New Sustainable Mineral Additions for the Manufacture of Eco-Cements.

Due to a continuously developing population, our consumption of one of the most widely used building materials, concrete, has increased. The production of concrete involves the use of cement whose production is one of the main sources of CO2 emissions; therefore, a challenge for today's society is to move towards a circular economy and develop building materials with a reduced environmental footprint. This study evaluates the possibility of using new sustainable supplementary cementitious materials (SCMs) from waste such as recycled concrete aggregates (RCAs) and mixed recycled aggregates (MRAs) from construction and demolition waste, as well as bottom ash from olive biomass (BBA-OL) and eucalyptus biomass ash (BBA-EU) derived from the production of electricity. A micronisation pre-treatment was carried out by mechanical methods to achieve a suitable fineness and increase the SCMs' specific surface area. Subsequently, an advanced characterisation of the new SCMs was carried out, and the acquired properties of the new cements manufactured with 25% cement substitution in the new SCMs were analysed in terms of pozzolanicity, mechanical behaviour, expansion and setting time tests. The results obtained demonstrate the feasibility of using these materials, which present a composition with potentially reactive hydraulic or pozzolanic elements, as well as the physical properties (fineness and grain size) that are ideal for SCMs. This implies the development of new eco-cements with suitable properties for possible use in the construction industry while reducing CO2 emissions and the industry's carbon footprint.

Relationship of Frailty, Nutritional Status and Oral Health-Related Quality of Life in Mexico City Nursing Home Residents.

BACKGROUND: We aimed to identify the association among nutritional status, Oral Health-Related Quality of Life (OHRQoL) and frailty, and to estimate the mediation effect of these conditions between age and frailty in a group of Mexico City nursing home residents. METHODS: We conducted a cross-sectional study. Fried's phenotype criteria, Full Mini Nutritional Assessment, and General Oral Health Assessment Index was applied. RESULTS: The participants (n = 286) mean age was 82.4 (± 9.2) years. The prevalence of frailty was 58%, and the prevalence of malnutrition and the risk of malnutrition were 22.7% and 59.5%, respectively. A higher risk of frailty was associated with older age (p = 0.015), sex (women) (p = 0.041), poor nutritional status (p <0.001) and compromised OHRQoL (p <0.001). Approximately 40% of the effect of age on frailty was mediated by nutritional status and OHRQoL (p <0.05). CONCLUSION: A strong association between nutritional status and frailty was observed. Additionally, OHRQoL was associated with frailty. The effect of age on frailty was mediated by OHRQoL and nutritional status. Interventions targeted to improve nutritional status and oral health may contribute to preventing or delaying the onset of frailty.

SOD1 gene variants rs4817415, rs2070424, and rs1041740 and their association with breast cancer risk.

OBJECTIVE: The aim of this investigation was to determine the frequency and association of the variants rs4817415, rs2070424, and rs1041740 of the SOD1 gene in healthy women and breast cancer (BC) patients. PATIENTS AND METHODS: Genomic DNA samples from 146 healthy women and 130 patients with BC were analyzed. RESULTS: GG genotype (OR 2.54, 95% CI 1.31-4.91, p = 0.0073) and the G allele (OR 1.37, 95% CI 1.09-1.73, p = 0.007) of the rs2070424 variant and CC genotype (OR 1.67, 95% CI 1.04-0.2.70, p = 0.0444) and allele C (OR 1.58, 95% CI 1.09-2.29, p = 0.0183) of the rs1041740 variant of SOD1 gene were associated as risk factors for BC susceptibility relative to the control group. Study groups comparison of the stratification by menopausal status showed an association of susceptibility to BC risk with carriers of the GG genotype (OR 2.9, 95% CI 1.11-7.81, p = 0.042) of the rs2070424 variant and with the premenopausal status of the study group and the TT (OR 2.89, 95% CI 1.73-4.85, p = 0.001) genotype of the rs1041740 variant. Furthermore, differences were observed in the patients with BC who were carriers of the CC genotype of the rs4817415 variant with elevated Ki-67 (≥ 20%) and who presented lymph node metastasis and stage III-IV BC (p<0.05). Two common haplotypes were identified in the study groups: CAC (protective factor), and CGC (risk factor) (p<0.05). CONCLUSIONS: The rs2070424 and rs1041740 variants of the SOD1 gene and the CGC haplotype were associated as risk susceptibility factors of BC in this sample analyzed.

Sodium Selenite Diminished the Regulatory T Cell Differentiation In Vitro.

Sodium selenite modulates the activity of lymphocytes. It negatively regulates the suppressive activity of cells and increases the immune response. In this study, we evaluated whether the regulatory T cell differentiation was modulated by sodium selenite. The percentages of CD4+CD25+Foxp3+, CD4+CD25+, and CD4+CTLA-4+ cells in CD4+ T cells cultures stimulated with IL-2 and TGF-ß in the presence or absence of selenium, in the form of sodium selenite (2.0×10-6M), were evaluated by flow cytometry. The mRNA expression of TET2/3 enzymes and IL-10 was analyzed by RT-qPCR and the levels of IL-10 were measured by an ELISA. We observed a decrease in CD4+CD25+Foxp3+ and CD4+CTLA-4+ cells in presence of selenium. However, normal percentages were reached again after selenium removal. An increase in CD4+CTL4-4+ cells was detected in selenium-primed cell cultures in absence of IL-2 and TGF-ß. In addition, we observed a decrease in TET3 in presence of selenium. Finally, we observed an augment in IL-10 transcription and protein levels and relative expression of TET2 in cultures exposed to selenium. We suggest that selenium reversibly affects the regulatory T cell differentiation in vitro. Likewise, selenium may modulate Treg percentages promoting optimal immune responses and, at the same time, the expression of specific suppressor molecules.

Margetuximab with retifanlimab as first-line therapy in HER2+/PD-L1+ unresectable or metastatic gastroesophageal adenocarcinoma: MAHOGANY cohort A.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric and gastroesophageal adenocarcinoma (GEA) is globally treated with chemotherapy plus trastuzumab. Novel therapeutic strategies strive to not only optimize efficacy, but also limit toxicities. In MAHOGANY cohort A, margetuximab, an Fc-engineered, anti-HER2 monoclonal antibody (mAb) was combined with retifanlimab, an anti-programmed cell death protein 1 mAb, in the first-line HER2-positive/programmed death-ligand 1 (PD-L1)-positive GEA. PATIENTS AND METHODS: MAHOGANY cohort A part 1 is a single-arm trial to evaluate margetuximab plus retifanlimab in patients with HER2 immunohistochemistry 3+, PD-L1-positive (combined positive score ≥1%), and non-microsatellite instability-high tumors. Primary objectives for cohort A were safety/tolerability and the confirmed objective response rate (ORR). RESULTS: As of 3 August 2021, 43 patients were enrolled and received margetuximab/retifanlimab. Nine grade 3 treatment-related adverse events (TRAEs) were reported in eight (18.6%) patients and eight serious TRAEs in seven (16.3%) patients. There were no grade 4/5 TRAEs. Three patients discontinued margetuximab/retifanlimab because of immune-related adverse events. The ORR by independent assessment was 53% [21/40 (95% confidence interval (CI) 36.1-68.5)], with a median duration of response of 10.3 months (95% CI 4.6-not evaluable); disease control rate was 73% [29/40 (95% CI 56.1-85.4)]. The study sponsor discontinued the study in advance of the planned enrollment when it became apparent that the study design would no longer meet the requirements for drug approval because of recent advances in the treatment of GEA. CONCLUSIONS: The chemotherapy-free regimen of combined margetuximab/retifanlimab as first-line treatment in double biomarker-selected patients demonstrated a favorable toxicity profile compared with historical outcomes using chemotherapy plus trastuzumab. The ORR observed in this study compares favorably versus ORR observed with other chemotherapy-free approaches.

Safety and efficacy of HER2 blockade by trastuzumab-based chemotherapy-containing combination strategies in HER2+ gastroesophageal adenocarcinoma.

Since completion of the Trastuzumab for Gastric Cancer study, trastuzumab with doublet chemotherapy (a fluoropyrimidine and a platinum) has been the gold-standard first-line therapy for patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2-positive (HER2+) gastroesophageal adenocarcinoma (GEA). The safety and efficacy of 23 studies of first-line trastuzumab plus doublet chemotherapy, without checkpoint inhibitors (n = 19) or with checkpoint inhibitors (n = 4), conducted in patients with locally advanced unresectable or metastatic HER2+ GEA, including phase II/III, prospective, and retrospective observational studies, were summarized. In studies without checkpoint inhibitors, the median duration of trastuzumab treatment ranged from 19.5 to 39.0 weeks and from 15.3 to 30.0 weeks for chemotherapy. In studies with checkpoint inhibitors, the median duration of pembrolizumab/trastuzumab/chemotherapy was 30 weeks, and 18 weeks for chemotherapy. In studies without checkpoint inhibitors, treatment-emergent adverse events (TEAEs) of grade ≥3 ranged from 32% to 84%. Serious adverse events (SAEs) ranged from 15% to 39%. Adverse events resulting in discontinuation ranged from 0% to 30%. Treatment-related deaths occurred in 0%-9% of patients. In studies with checkpoint inhibitors, TEAEs of grade ≥3 were 57%. SAEs ranged from 31% to 38%. Adverse events resulting in discontinuation ranged from 5% to 24%. Treatment-related deaths occurred in 0%-3% of patients. In studies without checkpoint inhibitors, objective response rate (ORR) ranged from 39% to 82%, median progression-free survival (PFS) from 5.7 to 11.6 months, and median overall survival (OS) from 11.2 to 27.6 months. In studies with checkpoint inhibitors, ORR ranged from 39% to 86%, median PFS from 8.0 to 13.0 months, and median OS from 19.3 to 27.3 months. This review provides a historical benchmark on safety and efficacy of available first-line chemotherapy-based standard of care for patients with locally advanced unresectable or metastatic HER2+ GEA.

Biochemical methane potential of residual biomass for energy generation.

World's energy consumption has doubled in the last four decades, this demand has been covered by the usage of fossil fuels; which are an important source of greenhouse gases emissions, entailing climate change. An efficient less polluting management alternative is the anaerobic digestion (AD) process which generates biogas derived from organic matter. The methane contained at the biogas is considered a biofuel that can generate electricity and heat through its combustion. Biochemical Methane Potential (BMP) essays are standardized methodologies carried out to estimate the energy potential of an organic residue. After performing a BMP test for 13 residual biomass samples, it can be concluded that fresh livestock rumen and manure were the best substrates to generate higher biogas yields; ranging from 1119-1669 ml/g VSadded, with high methane content (65%

Expression of BAFF and BAFF receptors in primary Sjögren's syndrome patients with ectopic germinal center-like structures.

B cell-activating factor (BAFF) is an essential cytokine in primary Sjögren's syndrome (pSS) physiopathology. It has been reported that pSS patients develop germinal center-like (GC-like) structures in their minor salivary glands (MSGs). BAFF, BAFF-R, TACI, and BCMA expression was analyzed in MSGs from 29 subjects (nonspecific chronic sialadenitis and focal lymphocytic sialadenitis with the presence [pSS-GC(+)] or absence [pSS-GC(-)] of GC-like structures). Twenty-four percent of patients showed ectopic GC-like structures and a high focus score [p < 0.001 vs pSS-GC(-)]. BAFF serum levels (sBAFF) were high in pSS patients (p = 0.025 vs healthy subjects). However, the pSS-GC(-) group showed higher sBAFF levels than pSS-GC(+) patients. BAFF and BAFF-R glandular expression levels were higher in pSS-GC(+) patients, without significant differences compared to pSS-GC(-) patients. Soluble levels of BAFF correlated with anti-La/SSB antibodies and disease duration. Our results showed that BAFF could contribute to focal lymphocytic infiltration. The role of BAFF-binding receptors in MSGs is proposed as a mechanism for the possible establishment of ectopic GC-like structures and disease progression in some patients. In conclusion, this study supports previous evidence that considers the active BAFF system role in the pathogenesis of pSS and the need for strong biomarkers in this disease.

Deletion of the N-terminal domain of the yeast vacuolar (Na+ ,K+ )/H+ antiporter Vnx1p improves salt tolerance in yeast and transgenic Arabidopsis.

Cation/proton antiporters play a major role in the control of cytosolic ion concentrations in prokaryotes and eukaryotes organisms. In yeast, we previously demonstrated that Vnx1p is a vacuolar monovalent cation/H+ exchanger showing Na+ /H+ and K+ /H+ antiporter activity. We have also shown that disruption of VNX1 results in an almost complete abolishment of vacuolar Na+ /H+ exchange, but yeast cells overexpressing the complete protein do not show improved salinity tolerance. In this study, we have identified an autoinhibitory N-terminal domain and have engineered a constitutively activated version of Vnx1p, by removing this domain. Contrary to the wild type protein, the activated protein has a pronounced effect on yeast salt tolerance and vacuolar pH. Expression of this truncated VNX1 gene also improves Arabidopsis salt tolerance and increases Na+ and K+ accumulation of salt grown plants thus suggesting a biotechnological potential of activated Vnx1p to improve salt tolerance of crop plants.

Association Between Vitamin D and Adrenal Parameters with Metabolic and Inflammatory Markers in Polycystic Ovary Syndrome.

Vitamin D deficiency has been related with metabolic alterations in polycystic ovary syndrome (PCOS). As well, hyperactivation of adrenal axis can be programmed early in life and could be related later with PCOS development. Our aim was to establish the relationship between vitamin D and adrenal parameters with metabolic alterations and inflammation markers in PCOS. In 73 patients and 33 controls, 25-hydroxyvitamin D (25-OH-D), total and bioavailable testosterone (TT and bioT), androstenedione (A4), SHBG, cortisol, insulin, and C-reactive protein (hs-CRP) were determined; HOMA and lipid accumulation product (LAP) index were calculated. All parameters were higher in patients than in controls, except for SHBG and 25-OH-D which were lower. Binary regression analysis showed that differences in TT, bioT, A4, insulin and HOMA were independent of body mass index and waist circumference but SHBG, hs-CRP, LAP and 25-OH-D were related to body weight and fat distribution. Binary logistic regression analysis showed that cortisol and 25-OH-D could be associated to PCOS development. Correlations found between LAP and insulin, HOMA and hs-CRP confirm it is a good indicator of metabolic complications. Vitamin D and cortisol association to PCOS development justifies future research to understand the role of vitamin D in PCOS and analyze patient's perinatal history and its possible relationship with hyperactivation of adrenal axis in adult life.

High BAFF expression associated with active disease in systemic lupus erythematosus and relationship with rs9514828C>T polymorphism in TNFSF13B gene.

B cell-activating factor (BAFF) promotes the survival, proliferation and maturation of B lymphocytes, which are key elements in the pathogenesis of systemic lupus erythematosus (SLE). This cytokine is encoded on TNFSF13B gene, and diverse single-nucleotide polymorphisms have been associated with susceptibility in different autoimmune disorders. In this study, the relationship of TNFSF13B gene rs9514827T>C, rs1041567T>A and rs9514828C>T polymorphisms, mRNA expression and soluble BAFF levels was investigated in 175 SLE patients and 208 healthy controls (HC). The TNFSF13B polymorphisms were evaluated by PCR-RFLP technique. The TNFSF13B gene expression was quantified through the RT-PCR assays. The soluble BAFF (sBAFF) levels were measured with ELISA test. There were no differences in genotype and allele frequencies for the three TNFSF13B polymorphisms, between SLE patients and HC. SLE patients showed 3.15-fold more TNFSF13B gene expression than HC. The patients who displayed most mRNA expression were those with active disease and the carriers of rs9514828 T variant allele. The sBAFF serum levels were higher in SLE patients compared to HC (2.083 vs. 0.742 ng/mL, p < 0.001). The SLE patients with active disease showed the higher sBAFF serum levels (2.403 ng/mL), mainly patients with lupus nephritis and hematological manifestations. In addition, a correlation of sBAFF with disease activity was found (r = 0.32, p < 0.001). In conclusion, the TNFSF13B gene polymorphisms were not found to be associated with SLE susceptibility in Mexican mestizos. Nevertheless, rs9514828C>T polymorphism seems to increase TNFSF13B gene expression. High BAFF expression is related to active disease, renal and hematological involvement; therefore, it could be considered as follow-up biomarker in SLE patients.

Overexpression of LeNHX2 and SlSOS2 increases salt tolerance and fruit production in double transgenic tomato plants.

Transgenic tomato plants (Solanum lycopersicum L. cv. MicroTom) overexpressing both the K+,Na+/H+ antiporter LeNHX2 and the regulatory kinase SlSOS2 were produced by crossing transgenic homozygous lines overexpressing LeNHX2 and SlSOS2. LeNHX2 expression was enhanced in plants overexpressing LeNHX2 but surprisingly even more in plants overexpressing SlSOS2 with and without LeNHX2. All transgenic plants showed better NaCl tolerance than wild type controls and plants overexpressing both LeNHX2 and SlSOS2 grew better under saline conditions than plants overexpressing only one of these genes. Yield related parameters indicated that single and above all double transgenic plants performed significantly better than wild type controls. All transgenic plants produced fruits with a higher K+ content than wild-type plants and plants overexpressing SlSOS2 accumulated more Na+ in fruits than the rest of the plants when grown with NaCl. Roots, stems and leaves of transgenic plants overexpressing LeNHX2 showed a higher K+ content than wild type and single transgenic plants overexpressing SlSOS2. Na+ content in stems and leaves of NaCl treated plants was higher in SlSOS2 overexpressing plants than in wild type and LeNHX2 single transgenic plants. All transgenic lines showed a higher leaf relative water content and a higher plant water content and water use efficiency than wild type controls when both were grown in the presence of NaCl. Results in this work indicate that the joint overexpression of LeNHX2 and SlSOS2 improves growth and water status under NaCl stress, affects K+ and Na+ homeostasis and enhances fruit yield of tomato plants.

Access to direct-acting antivirals for the treatment of hepatitis C in a country with limited resources. / Evaluación del acceso a antivirales para el tratamiento de la hepatitis C en un país con recursos limitados.

AIMS: To estimate the number of patients that have access to treatment of hepatitis C with direct-acting antivirals in Argentina and evaluate the factors associated with the lack of access. MATERIALS AND METHODS: A cross-sectional cohort study was conducted that included all the consecutive prescriptions of direct-acting antivirals issued at health centers that participated in the ECHOTM telemedicine project directed by the Hospital Italiano de Buenos Aires, within the time frame of January 2016 and February 2017. RESULTS: A total of 143 treatment prescriptions were included and overall access was 70% (95% CI 62-77%). The only independent factor associated with a lack of treatment access was coverage by a public healthcare system (OR 4.98 [95% CI 2.05- 12.09]). CONCLUSION: Patients with hepatitis C that were covered by a public healthcare system had a 4 times higher chance of not having access to treatment with direct-acting antivirals than patients covered by other healthcare systems (private insurance or the social welfare system).

Voltage-controlled interlayer coupling in perpendicularly magnetized magnetic tunnel junctions.

Magnetic interlayer coupling is one of the central phenomena in spintronics. It has been predicted that the sign of interlayer coupling can be manipulated by electric fields, instead of electric currents, thereby offering a promising low energy magnetization switching mechanism. Here we present the experimental demonstration of voltage-controlled interlayer coupling in a new perpendicular magnetic tunnel junction system with a GdOx tunnel barrier, where a large perpendicular magnetic anisotropy and a sizable tunnelling magnetoresistance have been achieved at room temperature. Owing to the interfacial nature of the magnetism, the ability to move oxygen vacancies within the barrier, and a large proximity-induced magnetization of GdOx, both the magnitude and the sign of the interlayer coupling in these junctions can be directly controlled by voltage. These results pave a new path towards achieving energy-efficient magnetization switching by controlling interlayer coupling.

Perspectiva de los pacientes sobre el tratamiento combinado de psicoterapia y farmacoterapia / Patients' perspective on combined treatment of psychotherapy and pharmacotherapy

La investigación sobre Tratamientos Combinados (TC) se ha centrado en estudiar los criterios que utilizan los profesionales a la hora de implementar este tipo de abordaje, pero son escasas las investigaciones que permitan conocer la perspectiva del paciente respecto a este tipo de tratamiento. Este es un estudio exploratorio, cualitativo conformada por 49 sujetos, residentes en CABA y GBA, que han recibido TC en los últimos dos años o lo están recibiendo en la actualidad, con el fin de evaluar los siguientes aspectos: 1) orientación teórica de profesionales; 2) comunicación entre profesionales; 3) efectos adversos de los tratamientos; y 4) experiencias de los pacientes respecto al TC. Los resultados preliminares sugieren que los pacientes en su mayoría conocen el tipo de tratamiento que realizan los psicólogos, siendo mucho menor el porcentaje de pacientes que conoce el tratamiento aplicado por su psiquiatra. En lo que respecta a informar los efectos adversos de los tratamientos son los psiquiatras quienes lo hacen en la mayoría de los casos pero es alta la cifra de pacientes que no han recibido esta información de ningún profesional tratante. Los pacientes presentan mayormente experiencias positivas respecto al TC basadas principalmente en la potenciación de los tratamientos y la contención de ambos profesionales. En lo que concierne a las experiencias negativas, la mala comunicación entre profesionales es la característica destacada. Este estudio se encuentra en proceso y sus conclusiones son provisionales.

Research on Combined Treatment (CT) is based largely on studies that seek to explore the criteria used by professionals involved in the combined therapies, though, there is little research exploring the perspective of CT users. We perform an exploratory qualitative study. A questionnaire was administered to 49 patients from CABA and GBA that are having CT or had been received it during the last two years to assess the following aspects: 1) professional´s theoretical orientation; 2) communication among professionals; 3) Side effects of treatments; and 4) patient experience regarding CT. Preliminary results suggest that most patients know the type of treatment carried out by psychologists, being lower the percentage of patients who know the psychiatric treatment. Regarding providing information about treatments side effects, psychiatrists reported in most cases, but there is a high number of patients who have not received this information from any treating professional. Concerning patient´s perspective on CT, the majority have positive experiences, being highlighted the empowerment of both treatments and professional care. On the other hand, bad communication between treating professionals were emphasized among negative experiences. This study is ongoing so its conclusions are tentative.

Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus.

OBJECTIVE: B-cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) signaling pathways regulate B-cell survival through interactions with their receptors BAFF-R, TACI and BCMA. We evaluated the association of these ligands/receptors on B-cell subsets according to clinical manifestations of systemic lupus erythematosus (SLE). METHODS: BAFF and APRIL serum concentrations were measured in 30 SLE patients by enzyme-linked immunosorbent assay. The BAFF-R, TACI and BCMA expression was analyzed on each B cell subset (CD19 + CD27-CD38-/ + naïve; CD19 + CD27 + CD38-/ + memory; CD19 + CD27-CD38 + + immature and CD19 + CD27 + CD38 + + plasma cells) by flow cytometry, and compared among patients with different clinical manifestations as well as healthy controls (HCs). RESULTS: Serum BAFF and APRIL levels were high in SLE patients and correlated with the Mex-SLEDAI disease activity index (r = 0.584; p = 0.001 and r = 0.456; p = 0.011, respectively). The SLE patients showed an increased proportion of memory and plasma B cells (p < 0.05). BAFF-R, TACI and BCMA expression in SLE patients was decreased in almost all B cell subsets compared to HCs (p < 0.05). A lower BCMA expression was associated with severe disease activity, glomerulonephritis, serositis and hemolytic anemia (p < 0.01). BCMA expression showed a negative correlation with Mex-SLEDAI score (r = -0.494, p = 0.006). CONCLUSIONS: Decreased BCMA expression on peripheral B cells according to severe disease activity suggests that BCMA plays an important regulating role in B-cell hyperactivity and immune tolerance homeostasis in SLE patients.

Manejo estomatológico de anemia de Fanconi en odontología pediátrica. Reporte de caso / Stomatological management of Fanconi anemia in pediatric dentistry. Case report

La anemia de Fanconi (FA) es una enfermedad autos6mica recesiva que se caracteriza por presentar anemia aplasica, además de malformaciones congénitas renales, cardiacas, esqueléticas, dermatológicas, y aumento en la incidencia de neoplasias malignas. Los pacientes con FA son más susceptibles de presentar sangrado e infecciones, síntomas relacionados con trombocitopenia y neutropenia. El prop6sito del presente reporte es describir el manejo estomato16gico proporcionado a un niño de 9 años y 9 meses de edad con diagn6stico de Anemia de Fanconi, en la Clínica del Posgrado en Estomatología Pediátrica...

Fanconi Anemia (FA) is an autosomal recessive disorder, characterized by aplastic anemia, congenital malformations in kidney, heart, skeletal and skin structures, and with increased incidence to malignancies. FA patients are likely to have bleeding and infections, which are associated with thrombocytopenia and neutropenia symptoms. The purpose of this paper is to report the stomatological management delivered to a child of 9 years and 9 months of age, diagnosed with Fanconi Anemia, in the clinic of Pediatric Dentistry...

Imidazole-containing phthalazine derivatives inhibit Fe-SOD performance in Leishmania species and are active in vitro against visceral and mucosal leishmaniasis.

The in vitro leishmanicidal activity of a series of imidazole-containing phthalazine derivatives 1-4 was tested on Leishmania infantum, Leishmania braziliensis and Leishmania donovani parasites, and their cytotoxicity on J774·2 macrophage cells was also measured. All compounds tested showed selectivity indexes higher than that of the reference drug glucantime for the three Leishmania species, and the less bulky monoalkylamino substituted derivatives 2 and 4 were clearly more effective than their bisalkylamino substituted counterparts 1 and 3. Both infection rate measures and ultrastructural alterations studies confirmed that 2 and 4 were highly leishmanicidal and induced extensive parasite cell damage. Modifications to the excretion products of parasites treated with 2 and 4 were also consistent with substantial cytoplasmic alterations. On the other hand, the most active compounds 2 and 4 were potent inhibitors of iron superoxide dismutase enzyme (Fe-SOD) in the three species considered, whereas their impact on human CuZn-SOD was low. Molecular modelling suggests that 2 and 4 could deactivate Fe-SOD due to a sterically favoured enhanced ability to interact with the H-bonding net that supports the antioxidant features of the enzyme.