Increased expression of cytokines, soluble cytokine receptors, soluble apoptosis ligand and apoptosis in dengue

AbstractSeveral studies have been performed to determine biomarkers that define the risk factors to developing severe forms of dengue. In this study, the levels of TNF-α, IL-6, IL-1, IL-17, soluble interleukin-1 receptor like 1 protein (sST2), soluble TNF-related apoptosis-inducing ligand (sTRAIL), IL-12 and soluble receptors for TNF (sTNF-RI and sTNF-RII) were determined by ELISA in dengue patients and monocyte/macrophage cultures. Dengue was classified as dengue without warning symptoms (DNWS), with warning symptoms (DWWS) and severe dengue (SD). High values of IL-6, sTNFRI, sTNFRII and sST2 were observed in DWWS and/or SD and IL-12 and sTRAIL in DNWS. TNF-α and IL-17 were increased not associated to the disease severity. High production of TNF-α, IL-1β, IL-12, IL-17, sST2 and sTRAIL and apoptosis expression were observed in dengue monocyte/macrophage cultures. This study shows that beneficial or deleterious biomarkers can be present in dengue regardless the disease severity and that monocytes may be in part the source of studied molecules

Effect of the failure criterion on the laboratory fatigue response prediction of hot mix asphalt mixtures

El objetivo principal de esta investigación fue establecer la influencia del criterio de fallo, empleado para calcular el comportamiento a fatiga en laboratorio de mezclas asfálticas en caliente especificadas por el Instituto de Desarrollo Urbano de Bogotá D.C. (i.e., mezclas md10 y md20), en la predicción de la respuesta a fatiga. Las leyes de fatiga (i.e., curvas de fatiga) se determinaron a flexo-tracción con muestras trapezoidales ensayadas a desplazamiento controlado. Los criterios utilizados para establecer la vida de fatiga correspondieron al clásico (50% de la fuerza inicial), de daño y de rotura. Los resultados correspondientes sugirieron que la selección del criterio de falla puede conllevar a diferencias significativas en la predicción de la vida de fatiga en laboratorio (i.e., curvas de fatiga). Sin embargo, se estableció que para las mezclas con granulometría densa md10, la ley de fatiga fue similar al emplear cualquiera de los tres criterios analizados. Por el contrario, para las mezclas asfálticas con granulometría densa md20, la aplicación de los tres criterios de falla conllevó a diferencias significativas en la predicción de vida de fatiga; el menor número de ciclos de carga a la falla (más crítico) fue determinado con el criterio clásico. Investigaciones futuras deberán profundizar en establecer que criterio de fallo se debe utilizar para el subsecuente diseño estructural de pavimentos, especialmente para mezclas asfálticas con curvas granulométricas que contengan agregados de tamaño igual o superior a 20 mm

Internal structure of laboratory compacted warm mix asphalt

Warm mix asphalt (WMA) are asphalt mixtures fabricated at lower temperatures (i.e., 20 C to 50 C) than conventional hot mix asphalt (HMA). Therefore, as compared to HMA, WMA offer several engineering, economical, and environmental advantages. However, research is still required to identify the response, properties, and performance of WMA, since they still constitute a relatively new technology. This paper focuses on the analysis of the internal structure of WMA specimens compacted using both the Superpave Gyratory Compactor (SGC) and the Texas Gyratory Compactor (TxGC). This analysis was conducted in terms of the air voids (AV) characteristics assessed by applying X-ray Computed Tomography and image analysis techniques. The results obtained suggest that the addition of WMA additives and corresponding reduction of the compaction temperature for SGC specimens did not lead to significant changes in the vertical distribution of total AV content as compared to that of the control-HMA. However, some differences were reported in terms of the AV size, which suggests the existence of discrepancies in the aggregate packing condition. Therefore, additional research is suggested to fully validate the equivalence of the internal structure of both WMA and HMA

Loss of Tumor Suppressor TMEM127 Drives Ret-Mediated Transformation Through Disrupted Membrane Dynamics

Internalization from the cell membrane and endosomal trafficking of receptor tyrosine kinases (RTKs) are important regulators of signaling in normal cells that can frequently be disrupted in cancer. The adrenal tumor pheochromocytoma (PCC) can be caused by activating mutations of the rearranged during transfection (RET) receptor tyrosine kinase, or inactivation of TMEM127, a transmembrane tumor suppressor implicated in trafficking of endosomal cargos. However, the role of aberrant receptor trafficking in PCC is not well understood. Here, we show that loss of TMEM127 causes wildtype RET protein accumulation on the cell surface, where increased receptor density facilitates constitutive ligand-independent activity and downstream signaling, driving cell proliferation. Loss of TMEM127 altered normal cell membrane organization and recruitment and stabilization of membrane protein complexes, impaired assembly, and maturation of clathrin-coated pits, and reduced internalization and degradation of cell surface RET. In addition to RTKs, TMEM127 depletion also promoted surface accumulation of several other transmembrane proteins, suggesting it may cause global defects in surface protein activity and function. Together, our data identify TMEM127 as an important determinant of membrane organization including membrane protein diffusability and protein complex assembly and provide a novel paradigm for oncogenesis in PCC where altered membrane dynamics promotes cell surface accumulation and constitutive activity of growth factor receptors to drive aberrant signaling and promote transformation

The Relationship between Depressive Symptoms, Quality of Life and miRNAs 8 Years after Bariatric Surgery

Altres ajuts: Universidad de Málaga, UMA20-FEDERJA-144; Junta de Andalucia, PI-0194-2017, C-0028-2018, RC-005-2020, DOC_00288 and DOC_01095Background: There are conflicting results on whether weight loss after bariatric surgery (BS) might be associated with quality of life (QoL)/depressive symptomatology. We aim to determine whether BS outcomes are associated with QoL/depressive symptomatology in studied patients at the 8-year follow-up after BS, as well as their relationship with different serum proteins and miRNAs. Methods: A total of 53 patients with class III obesity who underwent BS, and then classified into "good responders" and "non-responders" depending on the percentage of excess weight lost (%EWL) 8 years after BS (%EWL ≥ 50% and %EWL < 50%, respectively), were included. Basal serum miRNAs and different proteins were analysed, and patients completed tests to evaluate QoL/depressive symptomatology at 8 years after BS. Results: The good responders group showed higher scores on SF-36 scales of physical functioning, role functioning-physical, role functioning-emotional, body pain and global general health compared with the non-responders. The expression of hsa-miR-101-3p, hsa-miR-15a-5p, hsa-miR-29c-3p, hsa-miR-144-3p and hsa-miR-19b-3p were lower in non-responders. Hsa-miR-19b-3p was the variable associated with the response to BS in a logistic regression model. Conclusions: The mental health of patients after BS is limited by the success of the intervention. In addition, the expression of basal serum miRNAs related to depression/anxiety could predict the success of BS

Efecto antilipoperoxidante de Plukenetia volubilis L. (Sacha inchi) en ratas con diabetes inducida por aloxano.

Con el objetivo de  demostrar el efecto  antilipoperoxidante de   Plukenetia volubilis L. (Sacha Inchi). en ratas con diabetes inducida por aloxano. Método: se diseñó  un estudio experimental de casos y controles. 24 ratas con diabetes inducida por aloxano, fueron distribuida al azar en   4 grupos: (G0) Grupo control que recibieron 0,64 ml/kg de etanol,  (G1) Grupo estándar tratado con  de 0,25 ml/kg de vitamina E,  (G2) Grupo Experimental tratado con 120 mg/kg de extracto fluido de Sacha Inchi, (G3) Grupo Experimental tratado con  140 mg/kg de extracto fluido de Sacha Inchi.En todos los especímenes se determinó   nivel sérico de Malon dialdehido (MDA) uno basal y otro a los  16 días de iniciado el experimento.  Resultados: G1 mostró una reducción significativa de los niveles de Malondialdehido (MDA) sérico de 30% con respecto al control. El grupo G2, aproximadamente del 16.18% con respecto al control y el grupo G3 también mostró una reducción significativa del 23.5% con respecto al grupo control. Conclusión: la administración del extracto de hojas de Plukenetia Volubilis L in vivo tiene efecto antilipoperoxidante en ratas.  El mismo que es dependiente de  la dosis  administrada. Palabras clave: lipoperoxidación, glicemia, Plukenetia volubilis L., diabetes, estrés oxidativo

School of Public Accounting. Volume 16 No. 22 November 1991

Este informe es un estudio mundial, patrocinado por AICPA, que analiza el estado actual de la preparación y presentación de información financiera, a partir de lo cual propone los cambios que se requieren implementar.Editorial. Documentos. Profesores. Estudiantes.This report is a worldwide study, sponsored by AICPA, that analyzes the current state of the preparation and presentation of financial information, based on which it proposes the changes that need to be implemented

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: The ZIKAlliance consortium

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmissio

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life