De conformidad con Inglehart y su teoría de los valores post materiales respecto al activismo en general, la presente investigación tiene como objetivo explicar la influencia del activismo animalista ...en las políticas públicas de Loja-Ecuador para el período entre los años 2016 a 2020, la ideología que comparten y los datos cualitativos que motivan su operatividad. La metodología utilizada es de corte cualitativo y se combina con dos técnicas: la entrevista y el análisis de archivo. El marco teórico está compuesto por la sociología de la acción colectiva aplicada a los movimientos animalistas, además de un repaso histórico del activismo animalista en Ecuador y su influencia en el activismo animalista local, que da sentido a la teoría de Inglehart. La presente investigación permite comprender la influencia del activismo animalista y concluir que en Loja es uno de corte abolicionista, con una ideología bio céntrica, y cuyo accionar se ve influenciado por redes trasnacionales que giran en torno a temas sociales conflictivos relativos a la protección de los animales, especialmente canes.
Survival rates for pediatric acute leukemia vary dramatically worldwide. Infections are a leading cause of morbidity and mortality, and the impact is amplified in low and middle-income countries. ...Defining the epidemiology of infection in a specific health care setting is paramount to developing effective interventions. This study aimed to define the epidemiology of and outcomes from infection in children with acute leukemia treated in a large public pediatric hospital in the Dominican Republic. A retrospective cohort was assembled of children newly diagnosed with acute leukemia between July 1, 2015 to June 30, 2017 at Hospital Infantil Dr. Robert Reid Cabral in Santo Domingo. Patients were identified from the Pediatric Oncology Network Database (PONDTM) and hospital admissions from the Oncology admissions logbook. Medical records and microbiology results were reviewed to identify all inpatient invasive infections. Distance from a child's home to the hospital was determined using ArcGIS by Esri. Infection rates were described in discrete time periods after diagnosis and risk factors for invasive infection were explored using negative binomial regression. Overall, invasive infections were common and a prominent source of death in this cohort. Rates were highest in the first 60 days after diagnosis. Gastroenteritis/colitis, cellulitis, and pneumonia were most frequent, with bacteremia common early on. Multidrug resistant bacteria were prevalent among a small number of positive cultures. In a multivariate negative binomial regression model, age ≥ 10 years and distance from the hospital > 100 km were each protective against invasive infection in the first 180 days after diagnosis, findings that were unexpected and warrant further investigation. Over one-third of patient deaths were related to infection. Interventions aimed at reducing infection should target the first 60 days after diagnosis, improved supportive care inside and outside the hospital, and increased antimicrobial stewardship and infection prevention and control measures.
The search for new nutritional alternatives that favor human health is related to one of the world's tendencies in science and food technology nowadays: research on food with functional properties ...(antioxidant activity, prebiotic activity, intestinal motility, among others), mainly regions' autochthonous products, from which the productive sector can benefit thanks to its transformation and added value generation. In this review, the importance of four Andean food items with the potential to be explored and maximized by obtaining functional products is described. Because of the fact that blackberry, yacón, açaí and yellow pitahaya are promissory Andean foods with exceptional qualities for consumers' health, information was gathered about studies and possible effects in treatment of diseases, and the most used methods for the product and therefore for their biocompounds. It was concluded that this kind of food items represents important alternatives for the transformation and extraction of biocompounds (pigments, antioxidants, fructo-oligosaccharides, fiber, among others), in which non-thermal technologies play a fundamental role in conserving their functional properties, and at the same time, strengthen rural agro-industry and the exploitation of autochthonous products for strengthening region's and world's economy.
Heterotopic ossification (HO), the formation of ectopic bone in soft tissues, has been extensively studied in its two primary forms: post-traumatic HO (tHO) typically found in patients who have ...experienced musculoskeletal or neurogenic injury and in fibrodysplasia ossificans progressiva (FOP), where it is genetically driven. Given that in both diseases HO arises via endochondral ossification, the molecular mechanisms behind both diseases have been postulated to be manifestations of similar pathways including those activated by BMP/TGFβ superfamily ligands. A significant step towards understanding the molecular mechanism by which HO arises in FOP was the discovery that FOP causing ACVR1 variants trigger HO in response to activin A, a ligand that does not activate signaling from wild type ACVR1, and that is not inherently osteogenic in wild type settings. The physiological significance of this finding was demonstrated by showing that activin A neutralizing antibodies stop HO in two different genetically accurate mouse models of FOP. In order to explore the role of activin A in tHO, we performed single cell RNA sequencing and compared the expression of activin A as well as other BMP pathway genes in tHO and FOP HO. We show that activin A is expressed in response to injury in both settings, but by different types of cells. Given that wild type ACVR1 does not transduce signal when engaged by activin A, we hypothesized that inhibition of activin A will not block tHO. Nonetheless, as activin A was expressed in tHO lesions, we tested its inhibition and compared it with inhibition of BMPs. We show here that anti-activin A does not block tHO, whereas agents such as antibodies that neutralize ACVR1 or ALK3-Fc (which blocks osteogenic BMPs) are beneficial, though not completely curative. These results demonstrate that inhibition of activin A should not be considered as a therapeutic strategy for ameliorating tHO.
...despite the authors recognizing that the magnitude of contribution of cerebral vasospasm to poor outcome is debatable, they still solely rely on atrial narrowing of cerebral vessels as the trigger ...to therapeutic intervention without the inclusion of clinical deterioration as an additional trigger 3, 5. In our opinion, this contradiction remains a challenge. Because cerebral vasospasm alone is the trigger for treatment, the authors do not report the rate of patients without clinical deterioration included in either treatment group or the rate of patients with DCI despite absence of vasospasm that were excluded from treatment. Because high morbidity and mortality rates are associated with DCI with cerebral vasospasm, it makes sense that this should be the trigger for treatment with IV milrinone, especially with the hypothesis that milrinone’s mechanism of action is multifactorial in this setting 2. ...we acknowledge the lack of consensus regarding the definition of vasospasm-related infarcts, which makes it difficult to compare between-study findings 3, 5. ...it is important to consider more radiological variables regarding the vascular distribution and to narrow the definition of vasospasm-related infarcts.
Introduction
Approximately 15% of diffuse large B-cell lymphomas (DLBCL) do not respond to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) or equivalent regimen. These ...primary refractory cases (prDLBCL) have a particularly poor survival. There are currently no reliable biomarkers to a priori identify prDLBCL patients and include them in clinical trials, while avoiding needless toxicity from predictably ineffective therapy. In this study, we evaluated the potential for radiomic analysis with machine learning for predicting prDLBCL.
Method
This study included adult patients with prDLBCL from a single institution from 2009 to 2018, who had first-line treatment with an R-CHOP like regimen, had never received systemic treatment for indolent lymphoma, and who had a CT scan at the time of diagnosis. Refractory (R) patients were defined by progression of disease (PD) after completion of at least one cycle, or failure to achieve a complete response (CR) after at least 4 cycles, as per Lugano criteria (Cheson, JCO 2014). Non-refractory (NR) patients were matched 1:1 on sex and R-IPI for the comparison group. Enlarged lymph nodes (≥1.5 cm in greatest diameter) were eligible for evaluation. The 6 largest nodes were selected at each node site (abdomen, chest, axilla and neck) and for each node category (refractory node (RN), partial response (PR) and CR, as per Lugano criteria).
3D Slicer software was used for the delineation of the region of interest (ROI) either for subsequent 2D analysis (largest axial section) or 3D analysis (total node volume). Each node was manually contoured by two independent readers and also was reviewed by an experienced senior oncologic radiologist. A total of 788 and 1218 features were extracted from 2D and 3D regions of interest, respectively, using Pyradiomics open source software.
Two independent machine learning approaches, Random Forests (RF) and Support Vector Machine (SVM), were tested for constructing the prediction models. 70% of cases were randomly assigned to the training set and 30% to the independent testing set. In the node model (NM) each independent node's response to treatment was predicted. In the patient model (PM), groups of nodes per site (abdomen, chest, axilla and neck) were used to predict the overall patient response.
Results
A total of 26 refractory patients were identified with a total 149 nodes (RN=55, PR=20, CR=74) and matched to 26 NR patients for comparison, with a total of 105 CR nodes. Seventeen nodes with significant artifact were excluded from the analysis (7 from NR patients and 10 from R patients).
RF had consistently superior performance compared to SVM and was used for constructing the final prediction models. Furthermore, 2D radiomic analysis had superior performance compared to 3D radiomic analysis. In the independent testing (prediction) set, the mean accuracy between the 2 readers for this model for distinguishing a R from NR patient was 80% (mean sensitivity and specificity, 73% and 88%, respectively). This model was able to predict a R patient (positive predictive value (PPV)) in 100% and 71% of the case, respectively for readers 1 and 2. The area under the ROC curve (AUC) was 0.96 and 0.81 for reader 1 and 2, respectively (Figure 1A).
For performance of the radiomic model for distinguishing individual refractory from responsive nodes, the independent testing set had a mean accuracy of 75% (mean sensitivity, specificity, PPV, and NPV of 80%, 69%, 78%, and 71% respectively). The AUC per reader were 0.82 and 0.85 (Figure 1B).
Conclusion
We demonstrate that the use of CT radiomic analysis with machine learning for identifying a priori primary refractory DLBCL patients is feasible. These models provide a relatively high prediction accuracy, which currently cannot be done in the clinical setting based on standard, largely qualitative, imaging characteristics.
The main limitations of our study include small patient numbers in this pilot study and exclusion of extranodal sites. The next step for this project would be to evaluate this approach in a larger cohort that includes a second independent institution. CT-based radiomics is promising and should be further explored to achieve this unmet need for predicting prDLBCL prior to therapy initiation.
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Forghani:GE Healthcare: Consultancy, Honoraria, Research Funding; 4Intel Inc: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: Founder. Reinhold:FRQS: Other: FRQS Grant. Assouline:Pfizer: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria.
Aplicaciones terapéuticas del eculizumab Campos-González, Natalia; Ruiz-Jiménez, Susana; Rodríguez-Jiménez, Johanna ...
Universidad y salud,
08/2022, Volume:
24, Issue:
2
Journal Article
Peer reviewed
Open access
Introducción: El eculizumab es un anticuerpo monoclonal de tipo IgG diseñado para el tratamiento de la hemoglobinuria paroxística nocturna (HPN), en el que su diana farmacológica forma parte del ...sistema del complemento. Su mecanismo de acción ha permitido implementarlo en el tratamiento de enfermedades huérfanas, como el síndrome urémico hemolítico atípico (SUHa), trastorno del espectro de la neuromielitis óptica (TENMO) y miastenia gravis, cuya incidencia, es baja. Asimismo, es viable en el tratamiento de Guillain Barré y el síndrome antifosfolípido catastrófico (CAPS). Objetivo: Evidenciar aplicaciones terapéuticas del eculizumab y beneficios más significativos en algunos padecimientos. Materiales y métodos: Se realizó búsqueda bibliográfica en el periodo 2010–2021, en bases de datos: Google Scholar, Science Direct, PubMed y Scielo, utilizando como palabra clave “eculizumab”. Posteriormente, se afinó la búsqueda utilizando palabras claves asociadas a enfermedades tratadas con este medicamento. Resultados: Se identificó el mecanismo de acción del fármaco y su efecto sobre la patogénesis de hemoglobinuria paroxística nocturna, síndrome urémico atípico, miastenia gravis generalizada refractaria, trastorno del espectro de la neuromielitis óptica, síndromes antifosfolípidos catastrófico y Guillain-Barré. Conclusiones: El eculizumab tiene una alta seguridad y capacidad para tratar y disminuir síntomas de diversas enfermedades que involucran el sistema del complemento.
Previously we reported the identification of a homozygous COL27A1 (c.2089G>C; p.Gly697Arg) missense variant and proposed it as a founder allele in Puerto Rico segregating with Steel syndrome (STLS, ...MIM #615155); a rare osteochondrodysplasia characterized by short stature, congenital bilateral hip dysplasia, carpal coalitions, and scoliosis. We now report segregation of this variant in five probands from the initial clinical report defining the syndrome and an additional family of Puerto Rican descent with multiple affected adult individuals. We modeled the orthologous variant in murine Col27a1 and found it recapitulates some of the major Steel syndrome associated skeletal features including reduced body length, scoliosis, and a more rounded skull shape. Characterization of the in vivo murine model shows abnormal collagen deposition in the extracellular matrix and disorganization of the proliferative zone of the growth plate. We report additional COL27A1 pathogenic variant alleles identified in unrelated consanguineous Turkish kindreds suggesting Clan Genomics and identity-by-descent homozygosity contributing to disease in this population. The hypothesis that carrier states for this autosomal recessive osteochondrodysplasia may contribute to common complex traits is further explored in a large clinical population cohort. Our findings augment our understanding of COL27A1 biology and its role in skeletal development; and expand the functional allelic architecture in this gene underlying both rare and common disease phenotypes.
Yellow Pitahaya (YP) is an exotic fruit, cataloged by Colombia International Corporation as a promising fruit to export, due to its sensorial and organoleptic attributes. In addition, this fruit has ...been associated with the control of constipation, and benefits for health because of its content of antioxidants. Therefore, the purpose of this work was to determine its chemical and biocompounds present in stem, peel, seed, and pulp of yellow pitahaya. The polyphenols were determined with the Folin-Ciocalteu method; the vitamin C content was determined using 2-nitroaniline; the antioxidant capacity was found with the ABTS and DPPH methods; and the peristalsis acceleration by measuring feces in biomodels (golden hamster) fed with various parts of this fruit. The results proved that the fruit composition varies according to its part. It is noteworthy that all parts of the fruit contain bioactive compounds in various proportions; the highest concentration of vitamin C, polyphenols and antioxidant capacity (AC) were found in the seed (22.08 mg ascorbic acid per g dry matter, 1580 mg gallic acid per 100 g dry matter, 79.2±0.2% ABTS, respectively) and peel (20.615 mg ascorbic acid per g dry matter, 1333.33 mg gallic acid per 100 g dry matter, 66.2±0.8% ABTS, respectively); regarding the peristalsis acceleration, the fecal production increased with the consumption of the seeds. Consequently, result showed that yellow pitahaya could be an alternative of a promising product due to its composition, and content of bioactive components of functional interest.
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