Significant advances have been achieved in recent years in the identification of the genetic and the molecular alterations of pancreatic ductal adenocarcinoma (PDAC). Despite this, at present the ...understanding of the precise mechanisms involved in the development and malignant transformation of PDAC remain relatively limited. Here, we evaluated for the first time, the molecular heterogeneity of PDAC tumors, through simultaneous assessment of the gene expression profile (GEP) for both coding and non-coding genes of tumor samples from 27 consecutive PDAC patients. Overall, we identified a common GEP for all PDAC tumors, characterized by an increased expression of genes involved in PDAC cell proliferation, local invasion and metastatic capacity, together with a significant alteration of the early steps of the cellular immune response. At the same time, we confirm and extend on previous observations about the genetic complexity of PDAC tumors as revealed by the demonstration of two clearly distinct and unique GEPs (e.g. epithelial-like vs. mesenchymal-like) reflecting the alteration of different signaling pathways involved in the oncogenesis and progression of these tumors. Our results also highlight the potential role of the immune system microenvironment in these tumors, with potential diagnostic and therapeutic implications.
Aim We previously published a study (1998–2008) of 624 patients showing the association of pre-transplant DSA with poor kidney allograft survival. The aim of the current study was to assess ...development of post-transplant DSA in patients with well-functioning grafts >8 years after transplantation in comparison to patients with failed grafts. Methods HLA typing (A, B, C, DR, DQ) of recipients and donors was performed by standard serologic and/or DNA (SSP or SSO) methods. Anti-HLA antibody specificity was determined by single antigen beads (Lifecodes) on a Luminex platform. Though donors were not typed for DPB1 or DPA1 the de novo development of antibodies to DP alleles was presumed to be donor specific. Results Of 624 patients that were originally enrolled 131 were available for evaluation. 67 recipients had functioning kidney allografts 8 to 18 years after transplantation with >10 years follow up in 50% of these patients. The remaining 64 patients had graft failure (return to dialysis) with a median survival of 7.5 years. Of these patients, 44 (68%) had evidence of post-transplant DSA to HLA class 1 and/or class 2 as detected 0.1 to 5 years prior to graft failure. Most DSA positive recipients had antibodies to both Class 1 and 2 (32, 50%), whereas only 3 patients had DSA to Class 1 and only 9 patients had DSA to Class 2. Of patients with functioning grafts only 32% had evidence of DSA. In a new cohort transplanted in 2012–2015, that received identical induction and maintenance immunosuppression as the earlier cohort, similar DSA results were observed. Approximately, 33% of recipients with functioning kidney allografts had evidence of DSA whereas 65% of patients with failed grafts had DSA. In many cases, in both cohorts, the detection of a relatively low level of DSA occurred without concomitant clinical signs of rejection (e.g., a rise in creatinine). Conclusion As demonstrated in many studies of shorter duration the development of DSA was associated in this 18 year study with kidney allograft failure long after antibody has been detected and in the absence of standard clinical markers of rejection. Patients that exhibit persistent levels of DSA without clinical signs of rejection may benefit from enhanced immunosuppressive therapy to prevent damage to the kidney tubules and glomeruli that eventually lead to graft failure.
This article explores the meaning of national and international guidelines on childhood and their relation with educational projects in Colombia. A qualitative study was carried out using ...documentary, descriptive and analytical approaches. The methodology used was semantic content analysis, while the population consisted of official documents that have the purpose of providing guidelines for the formulation of public policies in Colombia and Latin America. The conclusion of the researchers was that childhood is only considered as an investment strategy that contributes to a country's economic development in the future, an investmentfor which the return comes when these children reach adulthood. Subsequently, the idea of childhood development is based on an instrumental educational proposal that is associated with a neoliberal logic based on human capital.
Lockdowns were one of the main preventive measures adopted by governments against the COVID-19 spread. Lockdowns changed people's routines and affected the activities of economic sectors in every ...country. Electric power sectors were also affected. The aim of this research is to determine the impact of preventive measures adopted by the Colombian government on the electric power demand of the main economic activities, using the difference-in-differences method and two-stage least squares estimation. In addition, a comparative analysis of the behaviour of the National Interconnected System total demand and disaggregated demand by markets in 2020, compared to previous years, was carried out. We evidence the recomposition of electricity consumption related to mandatory preventive isolation during the pandemic. The day with a more significant percentage difference compared with 2019 was April 10th, showing a decrease of 21.28 %. Therefore, this study contributes to improving the predictive models of the country's demand, optimizing the needs of future generations. Likewise, this study provides resources to optimize supplier portfolios and energy contracts for high-demand consumers.
•Impact of COVID-19 preventive measures on electricity demand in Colombia.•In 2020, Colombian electric power demand decreased by 2.1 % compared to 2019.•Energy demand growth rates were lower than Pre-COVID-19 estimates.•The socioeconomic gap and informality in Colombia increased.
The aim of this study was to compare the rate of sperm DNA fragmentation (rSDF; increase of SDF over time) in fresh and gradient isolated frozen-thawed semen samples from male sperm donors of proven ...fertility. SDF was assessed in the two samples obtained from the same fifteen male donors after 0.5, 1.5, 4.5, 6, 24, 48, and 72 h of incubation in a humidified atmosphere of 5% CO2 in air at 37°C. Analysis was performed based on chromatin dispersion patterns evaluated using the Halosperm® kit. No significant differences in SDF were obtained when fresh and gradient-isolated frozen-thawed spermatozoa were compared at baseline. However, the rSDF shown by the two samples differed and gradient-isolation selected for sperm subpopulations showing a lower variance for SDF. At the individual level, sperm selection by density gradient purification in frozen-thawed samples did not improve the levels of SDF when compared with the values obtained in fresh samples at baseline.
This scoping review aims to enhance construction project management practices by identifying the key factors contributing to time and cost overruns. More than 300 articles were studied, out of which ...73 were relevant to this review scope. Following the methodological recommendations proposed by the Joanna Briggs Institute (JBI) and the PRISMA checklist, this scoping review explores research trends regarding the geographical and temporal contexts, the nature of projects analyzed, the research approach, and the main causes of time and cost overruns. Moreover, current research gaps within the field have been identified. Findings suggest that the volume and breadth of research on causes of time and cost overruns have grown over the years. Regarding geographical contexts, Asia and Africa have consistently contributed to the literature, while a notable absence of research is observed in Europe, America, and Oceania. In addition, a tendency among articles to replicate research approaches and methods has been identified. Lastly, this study reveals that the project execution phase emerges as the primary stage where cost and time deviations occur, emphasizing the crucial role of project management practitioners. Hence, results attest to the critical role of prioritizing more effective project management practices to mitigate unexpected time and cost overruns in construction projects.
To describe the aortic-related risks associated with pregnancy in women with bicuspid aortic valve (BAV) and to evaluate changes in aortic diameter in pregnancy.
Prospective observational study of ...patients with BAV from a single-site registry of pregnant women with structural heart disease between 2013 and 2020. Cardiac, obstetric and neonatal outcomes were studied. An assessment of aortic dimensions was performed during pregnancy by two-dimensional echocardiography. Aortic diameters were measured at the annulus, root, sinotubular junction and maximum ascending aorta diameter, and the largest diameter was used. Measurements of the aorta were made using the end-diastolic leading edge-to-leading edge convention.
Forty-three women (32.9 years, IQR 29.6-35.3) with BAV were included: 9 (20.9%) had repaired aortic coarctation; 23 (53.5%) had moderate or severe aortic valve disease; 5 (11.6%) had a bioprosthetic aortic valve; and 2 (4.7%) had a mechanical prosthetic aortic valve. Twenty (47.0%) were nulliparous. The mean aortic diameter in the first trimester was 38.5 (SD 4.9) mm, and that in the third trimester was 38.4 (SD 4.8) mm. Forty (93.0%) women had an aortic diameter of <45 mm; 3 (7.0%) had 45-50 mm; and none had >50 mm. Three women (6.9%) with BAV presented cardiovascular complications during pregnancy or the postpartum period (two prosthetic thrombosis and one heart failure). No aortic complications were reported. There was a small but significant increase in aortic diameter during pregnancy (third trimester vs first trimester, 0.52 (SD 1.08) mm; p=0.03). Obstetric complications appeared in seven (16.3%) of pregnancies, and there were no maternal deaths. Vaginal non-instrumental delivery was performed in 21 (51.2%) out of 41 cases. There were no neonatal deaths, and the mean newborn weight was 3130 g (95% CI 2652 to 3380).
Pregnancy in BAV women had a low rate of cardiac complications with no aortic complications observed in a small study group. Neither aortic dissection nor need for aortic surgery was reported. A low but significant aortic growth was observed during pregnancy. Although requiring follow-up, the risk of aortic complications in pregnant women with BAV and aortic diameters of <45 mm at baseline is low.
To compare autoantibody-defined dermatomyositis sub-populations using immunoprecipitation-based assays, a commercially available line immunoblot assay and alternate commercial ELISA assays.
Banked ...plasma from 261 carefully phenotyped dermatomyositis patients was studied. Immunoprecipitation-based assays were used to detect antibodies against Mi2, TIF1-γ MDA5, NXP2, SAE1 and PM-Scl, while anti-Jo1 antibodies were assayed using ELISA. These data were compared with that obtained using a commercial line immunoblot, and, additionally, for Mi2, TIF1-γ, MDA5, commercially available ELISA kits. Test agreement was measured using Cohen's kappa statistic, and phenotypic differences between differentially identified groups are described.
Line immunoblot, immunoprecipitation, and ELISA detected increasingly larger nested pools of anti-TIF1-γ samples, with increasing frequency of concurrent anti-Mi2 reactivity and decreasing incidence of malignancy. Line immunoblot and immunoprecipitation showed fair concordance for identifying anti-NXP2 antibodies (Cohen's kappa=0.71) but very good agreement for identifying antibodies against Mi2, MDA5, and SAE1 (Cohen's κ=0.9, 0.94, 0.88, respectively). Anti-PM-Scl results showed moderate agreement (Cohen's κ=0.48) between immunoblot and immunoprecipitation.
Our results demonstrate that for some specificities, especially anti-TIF1-γ, antibody results obtained using different assay platforms vary, and identify significantly different patient populations. These findings highlight the need for standard adoption of carefully validated platforms to detect dermatomyositis autoantibodies.
PDF
