AbstractIntroductionIn Europe, gastric adenocarcinoma (GADC) is commonly regarded as a disease of the elderly. This study aims to assess the proportion, characteristics, and survival of patients ...diagnosed with GADC under the age of 60. Materials and methodsThis is a retrospective, multicentric, and analytical study conducted at four tertiary Spanish hospitals. All patients diagnosed with GADC between 2008 and 2015 were included. Demographic, clinical, endoscopic, histologic, and survival data were retrieved. A multivariate analysis was performed to compare GADC in young (age ≤ 60 years) and elderly patients. ResultsA total of 1374 patients with GADC were included. The mean age was 74 years (SD:11.1); 62.2% were males. There were 177 patients under the age of 60 (12.9%, 95% CI: 11.2–14.8%). GADC was frequently encountered as a metastatic disease in both young and elderly patients (Stage IV: 45.7% and 41%, respectively). In the multivariate analysis, alcohol abuse, ASA functional status I–II, diffuse subtype, neoadjuvant, and palliative therapy were independently associated ( P< 0.05) with age ≤60 years. No differences were found in 2-year survival (GADC ≤60: 39% vs. 35%, P= 0.45). Curative-intent surgery, TNM stage I-II, body mass index < 30 kg/m 2, and better functional status at diagnosis were independent predictors of survival in GADC under the age of 60. ConclusionsOne out of eight cases of GADC were diagnosed under the age of 60. Metastatic disease was frequent at diagnosis and overall survival was poor regardless of age. Factors associated with localized disease correlated with improved survival in younger patients. Our results underline the need for early diagnosis strategies in our country.
Introduction Bacteriophages have been shown to penetrate biofilms and replicate if they find suitable host cells. Therefore, these viruses appear to be a good option to tackle the biofilm problem and ...complement or even substitute more conventional antimicrobials. However, in order to successfully remove biofilms, in particular mature biofilms, phages may need to be administered along with other compounds. Phage-derived proteins, such as endolysins or depolymerases, offer a safer alternative to other compounds in the era of antibiotic resistance. Methods This study examined the interactions between phage Kayvirus rodi with a polysaccharide depolymerase (Dpo7) from another phage ( Rockefellervirus IPLA7 ) against biofilms formed by different Staphylococcus aureus strains, as determined by crystal violet staining, viable cell counts and microscopy analysis. Results and discussion Our results demonstrated that there was synergy between the two antimicrobials, with a more significant decreased in biomass and viable cell number with the combination treatment compared to the phage and enzyme alone. This observation was confirmed by microscopy analysis, which also showed that polysaccharide depolymerase treatment reduced, but did not eliminate extracellular matrix polysaccharides. Activity assays on mutant strains did not identify teichoic acids or PNAG/PIA as the exclusive target of Dpo7, suggesting that may be both are degraded by this enzyme. Phage adsorption to S. aureus cells was not significantly altered by incubation with Dpo7, indicating that the mechanism of the observed synergistic interaction is likely through loosening of the biofilm structure. This would allow easier access of the phage particles to their host cells and facilitate infection progression within the bacterial population.
Priorización de requisitos para una adecuada calidad de software Quiroz Martínez, Miguel; Leyva Vázquez, Maikel Yelandi; Jurado Antón, Ornella Andrea ...
Serie científica de la Universidad de las ciencias informáticas,
05/2020, Letnik:
13, Številka:
6
Journal Article
Recenzirano
Odprti dostop
The definition and analysis of the requirements of software are key factors for the final success of the projects of software specially for an appropriate quality of software. The prioritization of ...requirements of software, it is a process of taking of decisions, that in occasions returns complex, due to that in this prosecute decide the necessary functionalities to include in the product to develop and it is related with the quality of the software. This quality is measured for the capacitance that possesses the software to satisfy the needs of the clients and final users. The satisfaction by necessity implies contradiction a correct engineering that includes requirements specially of prioritization. Granting the priority to the requirements of software is a process that is not conceived sufficiently as for the flexibility and adaptability to the specific contexts of the organizations. The prioritization of requirements contributes to the identification of the wholes that they are critical for the success of the project of software, joined that they are located in the first iterations, and the other general remainder that are critical for the success of the project are considerate trivial and it is executed more late. This process permits arrange the total whole of requirements, which permits the general formation and your assignment of iterations. At present work, proposes the use of the prioritization of requirements of software, that does use of the addition operators in a hierarchical way, for an appropriate quality of the software.
La definición y análisis de los requisitos de software son factores claves para el éxito final de los proyectos de software en particular para una adecuada calidad de software. La priorización de requisitos de software, es un proceso de toma de decisiones, que en ocasiones se torna complejo, debido a que en este proceso se determinan las funcionalidades necesarias a incluir en el producto a desarrollar y se relaciona con la calidad del software. Esta calidad se mide por la capacidad que posee el software para satisfacer las necesidades de los clientes y usuarios finales. La satisfacción de necesidades implica una correcta ingeniería que incluye requisitos especialmente de priorización. Priorizar los requisitos de software es un proceso que no está concebido suficientemente en cuanto a la flexibilidad y adaptabilidad a los contextos específicos de las organizaciones. La priorización de requisitos contribuye a la identificación de los conjuntos que son críticos para el éxito del proyecto de software, conjuntos que se ubican en las primeras iteraciones, y el otro resto de conjuntos que son críticos para el éxito del proyecto son considerados triviales y se ejecutan más tardíos. Este proceso permite ordenar el conjunto total de requisitos, lo que permite la formación de subconjuntos y su asignación de iteraciones. En el presente trabajo, se propone el uso de la priorización de requisitos de software, que hace uso de los operadores de agregación de forma jerárquica, para una adecuada calidad del software.
Vaccination against measles, mumps, and rubella (MMR) and yellow fever (YF) with live attenuated viruses can rarely cause life-threatening disease. Severe illness by MMR vaccines can be caused by ...inborn errors of type I and/or III interferon (IFN) immunity (mutations in
,
, or
). Adverse reactions to the YF vaccine have remained unexplained. We report two otherwise healthy patients, a 9-yr-old boy in Iran with severe measles vaccine disease at 1 yr and a 14-yr-old girl in Brazil with viscerotropic disease caused by the YF vaccine at 12 yr. The Iranian patient is homozygous and the Brazilian patient compound heterozygous for loss-of-function
variations. Patient-derived fibroblasts are susceptible to viruses, including the YF and measles virus vaccine strains, in the absence or presence of exogenous type I IFN. The patients' fibroblast phenotypes are rescued with WT
Autosomal recessive, complete IFNAR1 deficiency can result in life-threatening complications of vaccination with live attenuated measles and YF viruses in previously healthy individuals.
La alimentación durante los dos primeros años tiene influencia directa sobre la calidad de vida de las personas, constituyéndose en factor protector o de riesgo para padecer enfermedades prevenibles ...en la adultez. El pediatra debería influir técnica y positivamente en las decisiones maternas sobre la alimentación de los infantes a fin de garantizar la nutrición y desarrollo adecuado. Objetivo: describir el nivel de conocimiento, actitudes y prácticas de alimentación de lactantes recomendadas por los pediatras de la comunidad. Metodología: estudio observacional, transversal, analítico tipo encuesta aplicado a pediatras en ejercicio en el eje metropolitano del estado Mérida-Venezuela, tanto en el sistema público como privado. Resultados: se incluyeron 52 pediatras, 75% femeninas, con edades mayores a 41 años; el 63,5% posee experiencia de crianza; 48,0% tiene más de 21 años de graduados, 70% con ejercicio mixto. 92% con un nivel de conocimiento intermedio, 100% en actitudes y prácticas. Se identificaron como tópicos susceptibles de entrenamiento: edad ideal para destete, edad de inicio de alimentación complementaria, porciones según edad, adición de grasas a los alimentos como estrategia de incremento de aporte calórico, incorporación oportuna de cereal de trigo o avena y huevo. Conclusión: los pediatras del estudio muestran conocimientos intermedios en alimentación del lactante, no incorporan ciertas recomendaciones dispuestas en los consensos, con una actitud y prácticas adecuadas. Se hace necesario promocionar la incorporación de las pautas establecidas como referencia para la práctica clínica diaria, mediante cursos de actualización y difusión por parte de las autoridades sanitarias y académicas.
The synthesis and characterization of (tBuPBP)Ni(OAc) (5) by insertion of carbon dioxide into the Ni−C bond of (tBuPBP)NiMe (1) is presented. An unexpected CO2 cleavage process involving the ...formation of new B−O and Ni−CO bonds leads to the generation of a butterfly‐structured tetra‐nickel cluster (tBuPBOP)2Ni4(μ‐CO)2 (6). Mechanistic investigation of this reaction indicates a reductive scission of CO2 by O‐atom transfer to the boron atom via a cooperative nickel‐boron mechanism. The CO2 activation reaction produces a three‐coordinate (tBuP2BO)Ni‐acyl intermediate (A) that leads to a (tBuP2BO)−NiI complex (B) via a likely radical pathway. The NiI species is trapped by treatment with the radical trap (2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl (TEMPO) to give (tBuP2BO)NiII(η2‐TEMPO) (7). Additionally, 13C and 1H NMR spectroscopy analysis using 13C‐enriched CO2 provides information about the species involved in the CO2 activation process.
An unexpected reactivity promoted by the ability of the PBP ligand to cooperate with the metal center is observed after the insertion of carbon dioxide into the Ni−C bond of (tBuPBP)NiMe. The overall process involves a complex reaction with the participation of NiII/NiI/Ni0 species that ultimately results in the formation of a nickel cluster with butterfly structure.
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Self-expandable metallic stents (SEMS) have been widely placed for unresectable distal malignant biliary obstruction (UDMBO). However, the dysfunction rate is 19–40% and its treatment ...is controversial. We aimed asses the efficacy and safety of a secondary biliary stents (uncovered (UC) versus fully-covered (FC) stent) for the management of occluded SEMS.
Between 2015 and June 2023, 41 patients with UDMBO underwent secondary biliary stent placement as “stent-in-stent” (20 FCSEMS and 21 UCSEMS). The primary outcomes were technical and clinical success of SEMS placement. Secondary outcomes included adverse events (AEs), patency and survival. Patients were prospectively followed until death or loss of follow-up.
Technical (100% vs 85.5%) and clinical (100% vs 95.2%) success rates were similar in FCSEMS and UCSEMS groups. The median follow-up period was 510 days (range 290–630). The median duration of stent patency of FCSEMS (220 days, IQR 137.5–442.5) was longer than UCSEMS (150 days, IQR 110–362.5) (P=0.395), although stent dysfunction within 6 months was not different between groups. Multivariate analysis indicated that sex (HR=0.909, 0.852–0.970), antitumor treatment (HR=0.248, 0.032–0.441), stent patency (HR=0.992, 0.986–0.998) and clinical success (HR=0.133, 0.026–0.690) were significant factors for overall survival. There were no remarkable differences in AEs.
The placement of additional biliary stent using the stent-in-stent method is an effective and safe rescue treatment for patients with UDMBO and occluded stent. In addition, the use of FCSEMS compared UCSEMS has unclear benefits regarding stent patency and overall survival.
Las prótesis metálicas autoexpandibles (PMA) son ampliamente utilizadas en el tratamiento de la obstrucción biliar distal maligna (OBDM) irresecable. La disfunción del stent es la complicación más frecuente y su manejo es controvertido. Nuestro objetivo es comparar la colocación de una segunda PMA-recubierta (PMA-R) frente a no recubierta (PMA-NR) coaxial en pacientes con obstrucción del stent.
Entre 2015-2023, se incluyeron 41 pacientes con OBDM que presentaron oclusión de PMA precisando de la colocación de una segunda PMA coaxial de rescate (20 PMA-R y 21 PMA-NR). Se definió permeabilidad de la PMA como el tiempo desde la colocación del segundo stent hasta su disfunción o muerte. Se analizó el éxito técnico, clínico y la seguridad según la PMA colocada.
Los éxitos técnico (100% vs. 85,5%) y clínico (100% vs. 95,2%) fueron similares en ambos grupos PMA-R y PMA-NR, respectivamente. La mediana de seguimiento fue de 510 días (rango 290-630). La mediana de permeabilidad de PMA-R (220 días, RIC 137,5-442,5) fue mayor que PMA-NR (150 días, RIC 110-362,5) (p=0,395). En el análisis multivariante, el sexo (HR=0,909, 0,852-0,970), el tratamiento antitumoral (HR=0,248, 0,032-0,441), la permeabilidad del stent (HR=0,992, 0,986-0,998) y el éxito clínico (HR=0,133, 0,026-0,690) fueron factores pronósticos estadísticamente significativos. No hubo eventos adversos graves.
La colocación de PMA coaxial es una técnica eficaz y segura en el tratamiento de OBDM y obstrucción del stent. Las PMA-R y PMA-NR coaxiales de rescate alcanzaron resultados comparables a largo plazo en términos de efectividad, permeabilidad y seguridad.
Abstract only
RATIONALE
Staphylococcus aureus
is a major cause of healthcare associated pneumonia and leads to high morbidity and mortality rates. Immune cells depend on glycolysis, particularly ...through Hif1α signaling, to drive pro‐inflammatory defenses to clear bacterial infections. We postulated that airway epithelial cells similarly use Hif1α stabilization and glycolysis to defend against
S. aureus
infection.
METHODS
A proteomic analysis of bronchoalveolar lavage fluid (BALF) from
S. aureus
USA300 infected C57BL/6 mice was performed comparing infected and uninfected mice. The metabolic and immunological consequences of Hif1a signaling were demonstrated in vitro. Human bronchial epithelial (16HBE) cells were studied through qRT arrays, western blots and ELISAs.
RESULTS
S. aureus
wild type USA300 (WT) were found to activate the canonical Hif1a and metabolic pathways that support glycolysis, as defined by the Ingenuity Pathway Analysis (IPA) of the secreted proteins in the BALF of infected mice. These results were verified in immunoblots demonstrating that
S. aureus
WT and toxin‐deficient
agr
mutants both stabilize Hif1α in 16HBE cells, despite significantly increased intracellular accumulation of the
agr
strain. Increased Hif1α corresponded with increased IL‐1b, IL‐8 and phosphofructokinase 1 (PFK1) transcript levels under infected conditions. The induction of HIF1a signaling, as a consequence of the metabolic stress caused by infection, was dependent on the glycolytic capacities of the bacteria, as a glycolytic mutant of
S. aureus
lacking pyruvate kinase (
pyk
) failed to induce Hif1α or secrete pro‐inflammatory cytokines IL‐1β and IL‐18. This was in contrast to WT and phosphoenolpyruvate kinase (
pckA
) deficient strains, with impaired gluconeogenesis.
CONCLUSIONS
The induction of epithelial glycolysis contributes to the metabolic and inflammatory response to
S. aureus
pulmonary infection. Both the organisms and the host use glycolysis to meet their increased metabolic requirements, promoting competition for glucose and stimulating Hif1a signaling. Our data highlights that metabolic stress is a driving factor in the host response to
S. aureus
in the lung, suggesting that manipulating metabolism might be a novel approach in the prevention and treatment of bacterial pneumonia.
Support or Funding Information
FUNDING: NIH R35 HL135300
Human infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmission and fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or ...prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancement (ADE) in vitro and extend their half-lives. Here we report on prophylactic coadministration of the Fc-modified antibodies to pregnant rhesus macaques challenged three times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission, protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV.
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