Colorectal cancer is still unmanageable despite advances in target therapy. However, extracellular vesicles (EVs) have shown potential in nanomedicine as drug delivery systems, especially for ...modulating the immune cells in the tumor microenvironment (TME). In this study, M1 Macrophage EVs (M1EVs) were used as nanocarriers of oxaliplatin (M1EV1) associated with retinoic acid (M1EV2) and Libidibia ferrea (M1EV3), alone or in combination (M1EV4) to evaluate their antiproliferative and immunomodulatory potential on CT-26 and MC-38 colorectal cancer cell lines and prevent metastasis in mice of allograft and peritoneal colorectal cancer models. Tumors were evaluated by qRT-PCR and immunohistochemistry. The cell death profile and epithelial-mesenchymal transition process (EMT) were analyzed in vitro in colorectal cancer cell lines. Polarization of murine macrophages (RAW264.7 cells) was also carried out. M1EV2 and M1EV3 used alone or particularly M1EV4 downregulated the tumor progression by TME immunomodulation, leading to a decrease in primary tumor size and metastasis in the peritoneum, liver, and lungs. STAT3, NF-kB, and AKT were the major genes downregulated by of M1EV systems. Tumor-associated macrophages (TAMs) shifted from an M2 phenotype (CD163) to an M1 phenotype (CD68) reducing levels of IL-10, TGF-β and CCL22. Furthermore, malignant cells showed overexpression of FADD, APAF-1, caspase-3, and E-cadherin, and decreased expression of MDR1, survivin, vimentin, and PD-L1 after treatment with systems of M1EVs. The study shows that EVs from M1 antitumor macrophages can transport drugs and enhance their immunomodulatory and antitumor activity by modulating pathways associated with cell proliferation, migration, survival, and drug resistance.
Display omitted
•M1EV systems modulated the tumor progression in TME of CCR primary tumors.•M1EV4s reduced metastatic niches in the peritoneum, liver, and lungs.•M1EV systems improved immune response by upregulating CD8 lymphocytes in TME.•Increased antitumoral response by blocking M2TAM-stimulated STAT3/NF-κB/AKT signals.
Myocardial bridging (MB) is a common congenital abnormality that remains asymptomatic in a large proportion of patients. The peak of clinical manifestation occurs during the third and fourth decades ...of life. MB provokes myocardial ischemia through different mechanisms including supply-demand mismatch, endothelial dysfunction, coronary microvascular dysfunction and external mechanical compression. The association between MB and atherosclerotic disease is controversial. Recent studies established a significant association of MB with myocardial infarction and non-obstructive coronary artery disease. The first line medical treatment is based on beta-blockers and calcium channel blockers. Ivabradine is used in second line therapy. Invasive approaches involving percutaneous coronary intervention, coronary artery bypass graft and myotomy are performed in patients with symptoms refractory to maximally tolerated medical treatment. The choice of revascularization technique depends on anatomical characteristics, clinical condition and physician experience. Available data derived from anecdotal evidence view the lack of randomized clinical trials.
Posterior pelvic ring injuries (i.e., sacro-iliac joint dislocations, fracture-dislocations, sacral fractures, pelvic non-unions/malunions) are challenging injury patterns which require a significant ...level of surgical training and technical expertise. The modality of surgical management depends on the specific injury patterns, including the specific bony fracture pattern, ilio-sacral joint involvement, and the soft tissue injury pattern. The workhorse for posterior pelvic ring stabilization has been cannulated iliosacral screws, however, trans-sacral screws may impart increased fixation strength. Depending on injury pattern and sacral anatomy, trans-sacral screws can potentially be more beneficial than iliosacral screws. In this article, the authors will briefly review pelvic mechanics and discuss their rationale for ilio-sacral and/or trans-sacral screw fixation. Keywords: Iliosacral, Trans-sacral, Screw, Posterior pelvic ring, Pelvic fracture, Injury mechanism
Children spend over 6 h a day in schools and have higher asthma morbidity from school environmental exposures. The present study aims to determine indoor and outdoor possible sources affecting indoor ...PM2.5 in classrooms. Weeklong indoor PM2.5 samples were collected from 32 inner-city schools from a Northeastern U.S. community during three seasons (fall, winter and spring) during the years 2009 to 2013. Concurrently, daily outdoor PM2.5 samples were taken at a central monitoring site located at a median distance of 4974 m (range 1065–11,592 m) from the schools. Classroom indoor concentrations of PM2.5 (an average of 5.2 μg/m3) were lower than outdoors (an average of 6.5 μg/m3), and these averages were in the lower range compared to the findings in other schools' studies. The USEPA PMF model was applied to the PM2.5 components measured simultaneously from classroom indoor and outdoor to estimate the source apportionment. The major sources (contributions) identified across all seasons of indoor PM2.5 were secondary pollution (41%) and motor vehicles (17%), followed by Calcium (Ca)-rich particles (12%), biomass burning (15%), soil dust (6%), and marine aerosols (4%). Likewise, the major sources of outdoor PM2.5 across all seasons were secondary pollution (41%) and motor vehicles (26%), followed by biomass burning (17%), soil dust (7%), road dust (3%), and marine aerosols (1%). Secondary pollution was the greatest contributor to indoor and outdoor PM2.5 over all three seasons, with the highest contribution during spring with 53% to indoor PM2.5 and 45% to outdoor PM2.5. Lower contributions of this source during fall and winter are most likely attributed to less infiltration indoors. In contrast, the indoor contribution of motor vehicles source was highest in the fall (29%) and winter (25%), which was presumably categorized by a local source. From the relationship between indoor-to-outdoor sulfur ratios and each source contribution, we also estimated the local and regional influence on indoor PM2.5 concentration. Overall, the observed differences to indoor PM2.5 are related to seasonality, and the distinct characteristics and behavior of each classroom/school.
•Relative source contributions of indoor and outdoor PM2.5 were determined for inner-city school classrooms;•Four outdoor sources and two indoor sources were identified as contributors to indoor PM2.5 concentrations, and;•Regional sources were the greatest contributor to indoor and outdoor PM2.5 in all seasons.
Control of N-nitrosoamine impurities is important for ensuring the safety of drug products. Findings of nitrosamine impurities in some drug products led FDA to develop new guidance providing ...recommendations for manufacturers towards prevention and detection of nitrosamine impurities in pharmaceutical products. One of these products, ranitidine, also had a published in vivo study, which has since been retracted by its authors, suggesting a potential for in vivo conversion of ranitidine to the probable human carcinogen, N-nitrosodimethylamine (NDMA). FDA subsequently initiated a randomized, double-blind, placebo-controlled, crossover clinical investigation to assess the potential for in vivo conversion of ranitidine to NDMA with different meals. A bioanalytical method toward characterization of NDMA formation was needed as previously published methods did not address potential NDMA formation after biofluid collection. Therefore, a bioanalytical method was developed and validated as per FDA's Bioanalytical Method Validation guidance. An appropriate surrogate matrix for calibration standards and quality control sample preparation for both liquid matrices (human plasma and urine) was optimized to minimize the artifacts of assay measurements and monitor basal NDMA levels. Interconversion potential of ranitidine to NDMA was monitored during method validation by incorporating the appropriate quality control samples. The validated methods for NDMA were linear from 15.6 pg/mL to 2000 pg/mL. Low sample volumes (2 mL for urine and 1 mL for plasma) made this method suitable for clinical study samples and helped to evaluate the influence of ranitidine administration and meal types on urinary excretion of NDMA in human subjects.
Display omitted
Introduction
Gastric cancer is the fifth most common malignant neoplasm and the third leading cause of cancer‐related death worldwide. In Peru, its incidence is 15.8 per 100,000 population, and it is ...associated with high mortality rates, especially in areas with low socioeconomic status. The aim of this study was to compare preoperative, postoperative, and anatomopathological staging results and their relation to disease recurrence and survival.
Methods
We conducted a retrospective cohort study of patients undergoing surgery for gastric cancer with a definitive postoperative anatomopathological diagnosis from 2005 to 2014 at the Hospital Nacional Luis N. Sáenz. Statistical analyses included descriptive and correlation statistics using the κ index, determination of associations between preoperative and postoperative staging and surgical reintervention and recurrence using the χ2 test, as well as Kaplan Meier survival analysis.
Results
There was little correlation between preoperative staging and final anatomopathological diagnosis, while there was a good correlation with postoperative staging. A significant association was found between preoperative staging and cancer recurrence. In the survival analysis, survival was lower among patients with underestimated staging.
Conclusions
The survival of patients with gastric cancer can be affected by an overestimation of preoperative staging, therefore improvements in preoperative staging could lengthen the survival of patients undergoing gastric cancer surgery.
We develop a new rationale for capital allocation in business groups’ internal capital markets. We show that productivity and pledgeable income jointly drive capital allocation within an internal ...capital market. In financially constrained business groups, an efficient internal capital market can allocate marginal funds to firms that have high pledgeability of income because of a multiplier effect: a dollar of internal funds generates a bigger increase in investment. This result has important implications for the business group affiliation strategy. Whether or not a financially constrained but highly productive firm will benefit from group affiliation depends on its borrowing capacity vis-à-vis other affiliates.
Tehuanismo Matta Abbud, Alexa
Designio, Investigación en Diseño Gráfico y Estudios de la Imagen,
11/2021, Letnik:
3, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Desde los artistas viajeros hasta el presente, un sinfín de artistas se han dedicado a producir obras que representan a las mujeres de Tehuantepec, famosas por su participación activa en la economía ...y en la vida pública de la ciudad. Este repertorio de obras ha consolidado la manera en la que entendemos y percibimos a la cultura de Tehuantepec, lo que ha llevado a representar una violencia simbólica en contra de estas mujeres, pues ellas se han definido a través de la mirada de otros. Estas miradas comúnmente pueden ser fetichizantes y exotizantes, o que conlleva intereses políticos propios, alejándose de la “realidad”. El artículo presenta los resultados de una investigación que parte de los estudios de género, específicamente del feminismo interseccional, para problematizar las obras que se han creado sobre el tema y las implicaciones políticas que las formas pictóricas pueden llegar a tener, para así exponer las violencias que estos procesos implican.
•Pulp blackberry acted as plasticizer, improving elongation.•There was darkening of the films with blackberry pulp after their sterilization.•The arrowroot starch promoted formation of an organized ...and dense network.•The surface of films with blackberry pulp was rough compared to the control film.•The blackberry pulp changed color and physicochemical properties of the film.
The influence of the incorporation of blackberry pulp on properties of arrowroot starch films has been studied. The blackberry pulp transferred bioactive compounds, antioxidant capacity and color to arrowroot starch films. Increasing the concentration of blackberry pulp (from 0 to 40%, mass/mass of dry starch) in the film resulted in increased thickness (from 0.065 to 0.133 mm), increased elongation (from 3.18 to 13.59%), decreased tensile strength (from 22.71 to 3.97 MPa), increased water vapor permeability (from 3.62 to 4.60 g.mm/m2.day.kPa) and solubility in water (from 14.18 to 25.46%). The films were stable to different media, maintaining the same initial diameter dimensions after immersion in acidic, neutral and alkaline solutions, but their color intensity was reduced, probably due to the release of anthocyanins to the solutions. The films with blackberry pulp presented darkness after sterilization process.
PDF
