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Abstract The recent surge in the plant-based protein market has resulted in high demands for soybean genotypes with improved grain yield, seed protein and oil content, and essential amino acids (EAAs). Given the quantitative nature of these traits, complex interactions among seed components, as well as between seed components and environmental factors and management practices, add complexity to the development of desired genotypes. In this study, the across-environment seed protein stability of 449 genetically diverse plant introductions was assessed, revealing that genotypes may display varying sensitivities to such environmental stimuli. The EAAs valine, phenylalanine, and threonine showed the highest variable importance toward the variation in stability, while both seed protein and oil contents were among the explanatory variables with the lowest importance. In addition, 56 single nucleotide polymorphism (SNP) markers were significantly associated with various seed components. Despite the strong phenotypic Pearson’s correlation observed among most seed components, many independent genomic regions associated with one or few seed components were identified. These findings provide insights for improving the seed concentration of specific EAAs and reducing the negative correlation between seed protein and oil contents.

Cercospora leaf blight (CLB), caused by Cercospora cf. flagellaris, C. kikuchii, and C. cf. sigesbeckiae, is a significant soybean [Glycine max (L.) Merr.] disease in regions with hot and humid conditions causing yield loss in the United States and Canada. There is limited information regarding resistant soybean cultivars, and there have been marginal efforts to identify the genomic regions underlying resistance to CLB. A Genome-Wide Association Study was conducted using a diverse panel of 460 soybean accessions from maturity groups III to VII to identify the genomic regions associated to the CLB disease. These accessions were evaluated for CLB in different regions of the southeastern United States over 3 years. In total, the study identified 99 Single Nucleotide Polymorphism (SNPs) associated with the disease severity and 85 SNPs associated with disease incidence. Across multiple environments, 47 disease severity SNPs and 23 incidence SNPs were common. Candidate genes within 10 kb of these SNPs were involved in biotic and abiotic stress pathways. This information will contribute to the development of resistant soybean germplasm. Further research is warranted to study the effect of pyramiding desirable genomic regions and investigate the role of identified genes in soybean CLB resistance.

Abstract Breeding for increased protein without a reduction in oil content in soybeans [Glycine max (L.) Merr.] is a challenge for soybean breeders but an expected goal. Many efforts have been made to develop new soybean varieties with high yield in combination with desirable protein and/or oil traits. An elite line, R05‐1415, was reported to be high yielding, high protein, and low oil. Several significant quantitative trait loci (QTL) for protein and oil were reported in this line, but many of them were unstable across environments or genetic backgrounds. Thus, a new study under multiple field environments using the Infinium BARCSoySNP6K BeadChips was conducted to detect and confirm stable genomic loci for these traits. Genetic analyses consistently detected a single major genomic locus conveying these two traits with remarkably high phenotypic variation explained (R2), varying between 24.2% and 43.5%. This new genomic locus is located between 25.0 and 26.7 Mb, distant from the previously reported QTL and did not overlap with other commonly reported QTL and the recently cloned gene Glyma.20G085100. Homolog analysis indicated that this QTL did not result from the paracentric chromosome inversion with an adjacent genomic fragment that harbors the reported QTL. The pleiotropic effect of this QTL could be a challenge for improving protein and oil simultaneously; however, a further study of four candidate genes with significant expressions in the seed developmental stages coupled with haplotype analysis may be able to pinpoint causative genes. The functionality and roles of these genes can be determined and characterized, which lay a solid foundation for the improvement of protein and oil content in soybeans.

Abstract Background The epidermal growth factor receptor (EGFR) is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC. Results In this study we explored the potential of combining either erlotinib with cetuximab or trastuzumab to improve the efficacy of EGFR targeted therapy in EGFR wild-type NSCLC cell lines. Erlotinib treatment was observed to increase EGFR and/or HER2 expression at the plasma membrane level only in NSCLC cell lines sensitive to the drug inducing protein stabilization. The combined treatment had marginal effect on cell proliferation but markedly increased antibody-dependent, NK mediated, cytotoxicity in vitro. Moreover, in the Calu-3 xenograft model, the combination significantly inhibited tumour growth when compared with erlotinib and cetuximab alone. Conclusion Our results indicate that erlotinib increases surface expression of EGFR and/or HER2 only in EGFR-TKI sensitive NSCLC cell lines and, in turns, leads to increased susceptibility to ADCC both in vitro and in a xenograft models. The combination of erlotinib with monoclonal antibodies represents a potential strategy to improve the treatment of wild-type EGFR NSCLC patients sensitive to erlotinib.

Abstract Background Gefitinib is a tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) especially effective in tumors with activating EGFR gene mutations while EGFR wild-type non small cell lung cancer (NSCLC) patients at present do not benefit from this treatment. The primary site of gefitinib metabolism is the liver, nevertheless tumor cell metabolism can significantly affect treatment effectiveness. Results In this study, we investigated the intracellular metabolism of gefitinib in a panel of EGFR wild-type gefitinib-sensitive and -resistant NSCLC cell lines, assessing the role of cytochrome P450 1A1 (CYP1A1) inhibition on gefitinib efficacy. Our results indicate that there is a significant difference in drug metabolism between gefitinib-sensitive and -resistant cell lines. Unexpectedly, only sensitive cells metabolized gefitinib, producing metabolites which were detected both inside and outside the cells. As a consequence of gefitinib metabolism, the intracellular level of gefitinib was markedly reduced after 12-24 h of treatment. Consistent with this observation, RT-PCR analysis and EROD assay showed that mRNA and activity of CYP1A1 were present at significant levels and were induced by gefitinib only in sensitive cells. Gefitinib metabolism was elevated in crowded cells, stimulated by exposure to cigarette smoke extract and prevented by hypoxic condition. It is worth noting that the metabolism of gefitinib in the sensitive cells is a consequence and not the cause of drug responsiveness, indeed treatment with a CYP1A1 inhibitor increased the efficacy of the drug because it prevented the fall in intracellular gefitinib level and significantly enhanced the inhibition of EGFR autophosphorylation, MAPK and PI3K/AKT/mTOR signalling pathways and cell proliferation. Conclusion Our findings suggest that gefitinib metabolism in lung cancer cells, elicited by CYP1A1 activity, might represent an early assessment of gefitinib responsiveness in NSCLC cells lacking activating mutations. On the other hand, in metabolizing cells, the inhibition of CYP1A1 might lead to increased local exposure to the active drug and thus increase gefitinib potency.

In this article we approach the dramatic text Wachay by the writer Cecilia Salman from Santiago del Estero; we are interested in reflecting on how the author constructs the feminine/animal/natural/sound universe anchored in popular stories of our northern soil. From a decolonial perspective, we will comment on the resignification of cultural texts of the region, through an original and localized fabric.

Optimisation of solar drying to reduce fungal growth and Ochratoxin A (OTA) contamination is a crucial concern in raisin and currant production. Stochastic and deterministic analysis has been utilized to investigate environmental indicators and drying characteristics. The analysis was performed using two seedless grape varieties (Crimson—red and Thompson—white) that were artificially inoculated with Aspergillus carbonarius during open-air and tunnel drying. Air temperature (T) and relative humidity (RH) were measured and analysed during the drying experiment, along with grape surface temperature (Ts), and water activity (aw). The grape moisture content, fungal colonization, and OTA contamination were estimated, along with the water diffusivity (Deff) and peel resistance (rpeel) to water transfer. Monitoring the surface temperature of grapes is essential in the early detection of fungal growth and OTA contamination. As surface temperature should be carried out continuously, remote sensing protocols, such as infrared sensors, provide the most efficient means to achieve this. Furthermore, data collection and analysis could be conducted through the Internet of Things (IoT), thereby enabling effortless accessibility. The average Ts of the grapes was 6.5% higher in the tunnel than in the open-air drying. The difference between the RH of air and that in the plastic crates was 16.26–17.22%. In terms of CFU/mL, comparison between white and red grapes in the 2020 and 2021 experiments showed that the red grapes exhibited significantly higher values than the white grapes. Specifically, the values for red grapes were 4.3 in 2021 to 3.4 times in 2020 higher compared to the white grapes. On the basis of the conducted analysis, it was concluded that tunnel drying provided some advantages over open-air drying, provided that hygienic and managerial requirements are met.

The sucrose and Alanine (Ala) content in edamame beans significantly impacts the sweetness flavor of edamame-derived products as an important attribute to consumers’ acceptance. Unlike grain-type soybeans, edamame beans are harvested as fresh beans at the R6 to R7 growth stages when beans are filled 80-90% of the pod capacity. The genetic basis of sucrose and Ala contents in fresh edamame beans may differ from those in dry seeds. To date, there is no report on the genetic basis of sucrose and Ala contents in the edamame beans. In this study, a genome-wide association study was conducted to identify single nucleotide polymorphisms (SNPs) related to sucrose and Ala levels in edamame beans using an association mapping panel of 189 edamame accessions genotyped with a SoySNP50K BeadChip. A total of 43 and 25 SNPs was associated with sucrose content and Ala content in the edamame beans, respectively. Four genes (Glyma.10g270800, Glyma.08g137500, Glyma.10g268500, and Glyma.18g193600) with known effects on the process of sucrose biosynthesis and 37 novel sucrose-related genes were characterized. Three genes (Gm17g070500, Glyma.14g201100 and Glyma.18g269600) with likely relevant effects in regulating Ala content and 22 novel Ala-related genes were identified. In addition, by summarizing the phenotypic data of edamame beans from three locations in two years, three PI accessions (PI 532469, PI 243551, and PI 407748) were selected as the high sucrose and high Ala parental lines for the perspective breeding of sweet edamame varieties. Thus, the beneficial alleles, candidate genes, and selected PI accessions identified in this study will be fundamental to develop edamame varieties with improved consumers’ acceptance, and eventually promote edamame production as a specialty crop in the United States.

El proceso de envejecimiento poblacional que acontece en el mundo, y en especial en América Latina, vuelve fundamental colocar la mirada en las necesidades que presentan las y los adultos mayores en el desarrollo de esta etapa de su vida. El objetivo general de este artículo es caracterizar la existencia de los espacios de cuidados de las personas adultas mayores en el territorio nacional, a partir de datos del Censo Nacional de Hogares 2010 y del mapa Federal de Cuidados. Del total de establecimientos registrados, 13% son para personas mayores, y de ellos, 71,6% son instituciones privadas. Existe una distribución desigual de características socio-demográficas a nivel nacional, y esto genera una situación que puede aumentar la vulnerabilidad de la persona mayor e interferir en el poseer una adecuada calidad de vida.

Increasing reports of neurological and psychiatric outcomes due to psychostimulant synthetic cathinones (SCs) have recently raised public concern. However, the understanding of neurotoxic mechanisms is still lacking, particularly for the under-investigated αPHP, one of the major MDPV derivatives. In particular, its effects on neural stem/progenitor cell cultures (NSPCs) are still unexplored. Therefore, in the current in vitro study, the effects of increasing αPHP concentrations (25–2000 μM), on cell viability/proliferation, morphology/ultrastructure, genotoxicity and cell death pathways, have been evaluated after exposure in murine NSPCs, using a battery of complementary techniques, i.e., MTT and clonogenic assay, flow cytometry, immunocytochemistry, TEM, and patch clamp. We revealed that αPHP was able to induce a dose-dependent significant decrease of the viability, proliferation and clonal capability of the NSPCs, paralleled by the resting membrane potential depolarization and apoptotic/autophagic/necroptotic pathway activation. Moreover, ultrastructural alterations were clearly observed. Overall, our current findings demonstrate that αPHP, damaging NSPCs and the morpho-functional fundamental units of adult neurogenic niches may affect neurogenesis, possibly triggering long-lasting, irreversible CNS damage. The present investigation could pave the way for a broadened understanding of SCs toxicology, needed to establish an appropriate treatment for NPS and the potential consequences for public health.

Las enfermedades neuromusculares se caracterizan por debilidad muscular progresiva, que afecta la deambulación y el desempeño en actividades funcionales como las transferencias, correr, saltar, subir y bajar rampas o escaleras, entre otras. Para medir objetivamente el compromiso motor de los pacientes deambuladores, entre otras herramientas disponibles, existen las pruebas de tiempo o cronometradas, que valoran la velocidad para realizar determinadas tareas funcionales. En este trabajo se describen los procedimientos para realizar las cuatro pruebas cronometradas más utilizadas en la evaluación y el seguimiento de los pacientes neuromusculares deambuladores: pararse desde supino, marcha o carrera de 10 metros y subir y bajar 4 escalones.

Summary: The bioactivity of biomaterials is closely related to cell response in contact with them. However, shortly after their insertion, materials are soon covered with proteins that constitute the biological fluids, and which render the direct surface recognition by cells almost impossible. The control of protein adsorption at the interface is therefore desirable. Extracellular matrix proteins are of particular interest in this sense, due to their well-known ability to modulate cell behavior. Particularly, fibronectin plays a leading role, being present in both healthy and injured tissues undergoing healing and regeneration. The aim of the present work is to give an overview on fibronectin and on its involvement in the control of cell behavior providing evidence of its pivotal role in the control of cell adhesion, spreading, migration, proliferation and differentiation. A deep insight into methods to enrich biomaterials surface with fibronectin will be then discussed, as well as new cues on the possibility to design tailored platforms able to specifically retain fibronectin from the surrounding extracellular milieu.

The present study investigated the effects of contingency-specifying rules and a token economy to decrease the latency to comply with academic instructions by a 16-year-old girl with acquired brain injury. Results showed that treatment was successful in reducing academic response latencies. These results replicate previous research in which differential reinforcement was used to decrease slow responding to academic tasks. (Contains 1 figure.)

Women with pathogenic germline mutations in BRCA1 and BRCA2 genes have an increased risk to develop breast and ovarian cancer. There is, however, a high interpersonal variability in the modality and timing of tumor onset in those subjects, thus suggesting a potential role of other individual’s genetic, epigenetic, and environmental risk factors in modulating the penetrance of BRCA mutations. MicroRNAs (miRNAs) are small noncoding RNAs that can modulate the expression of several genes involved in cancer initiation and progression. MiRNAs are dysregulated at all stages of breast cancer and although they are accessible and evaluable, a standardized method for miRNA assessment is needed to ensure comparable data analysis and accuracy of results. The aim of this review was to highlight the role of miRNAs as potential biological markers for BRCA mutation carriers. In particular, biological and clinical implications of a link between lifestyle and nutritional modifiable factors, miRNA expression and germline BRCA1 and BRCA2 mutations are discussed with the knowledge of the best available scientific evidence.

Amyloid beta (Abeta) 1-42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer's disease (AD). We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic effects on synapses in vitro and cognitive deficits in vivo. Knockdown of sigma-2/PGRMC1 (progesterone receptor membrane component 1) protein expression in vitro using siRNA results in a highly correlated reduction in binding of exogenous Abeta oligomers to neurons of more than 90%. Expression of sigma-2/PGRMC1 is upregulated in vitro by treatment with Abeta oligomers, and is dysregulated in Alzheimer's disease patients' brain compared to age-matched, normal individuals. Specific, high affinity small molecule receptor antagonists and antibodies raised against specific regions on this receptor can displace synthetic Abeta oligomer binding to synaptic puncta in vitro and displace endogenous human AD patient oligomers from brain tissue sections in a dose-dependent manner. These receptor antagonists prevent and reverse the effects of Abeta oligomers on membrane trafficking and synapse loss in vitro and cognitive deficits in AD mouse models. These findings suggest sigma-2/PGRMC1 receptors mediate saturable oligomer binding to synaptic puncta on neurons and that brain penetrant, small molecules can displace endogenous and synthetic oligomers and improve cognitive deficits in AD models. We propose that sigma-2/PGRMC1 is a key mediator of the pathological effects of Abeta oligomers in AD and is a tractable target for small molecule disease-modifying therapeutics.

Soybean production in the U.S. Mid-South relies heavily on irrigation with 85% of soybean surfaces irrigated in Arkansas. Reduction in irrigation due to water quantity restrictions will significantly affect soybean seed yield, making variety selection increasingly important. The objective of the study was to assess if irrigation onsets at different reproductive stages affect wilting, seed yield, and key agronomic traits on determinate maturity group 5 (MG 5) soybean. One-hundred sixty-five F4-derived populations of recombinant inbred lines with determinate growth habit, similar maturity, and contrasting wilting potential were planted in an augmented strip-plot design in four environments as a single replicate. Four irrigation onsets were applied at R1 (initiation flower), R2 (full bloom), R3 (initiation pod), and R4 (full pod) using an atmometer. Results indicated significant differences in wilting and yield but no significant differences in maturity, protein, oil concentration, and 100-seed weight across different irrigation onsets. There was no significant difference between the fast and slow wilting genotypes across different irrigation onsets for each trait. Allowable depletions measured in this study indicated that both fast and slow wilting soybean genotype determinate MG5 can tolerate high allowable depletion with no significant yield penalty at R3 growth stage in silt loam soil.

Edamame is a food-grade soybean [Glycine max (L.) Merr.] that is harvested immature between the R6 and R7 reproductive stages. To be labeled as a premium product, the edamame market demands large pod size and intense green color. A staggered harvest season is critical for the commercial industry to post-harvest process the crop in a timely manner. Currently, there is little information to assist in predicting the optimum time to harvest edamame when the pods are at their collective largest size and greenest color. The objectives of this study were to assess the impact of cultivar, planting date, and harvest date on edamame color, pod weight, and a newly minted Edamame Harvest Quality Index combining both aforementioned factors. And to predict edamame harvest quality based on phenological stages, thermal units, and planting dates. We observed that pod color and weight depended on the cultivar, planting date, and harvest date combination. Our results also indicated that edamame quality is increased with delayed planting dates and that quality was dependent on harvest date with a quadratic negative response to delaying harvest. Maximum quality depended on cultivar and planting and harvest dates, but it remained stable for an interval of 18–27 days around the peak. Finally, we observed that the number of days between R1 and harvest was consistently identified as a key factor driving edamame quality by both stepwise regression and neural network analysis. These research results will help define a planting and harvest strategy for edamame production in Arkansas and the United States Mid-South.

The prognosis of patients affected by malignant pleural mesothelioma (MPM) is presently poor and no therapeutic strategies have improved their survival yet. Introduction of miRNA mimics to restore their reduced or absent functionality in cancer cells is considered an important opportunity and a combination of miR's might be even more effective. In the present study, miR-16 and miR-34a were transfected, singularly and in combination, in MPM cell lines H2052 and H28, and their effects on cell proliferation and sensitivity to cisplatin are reported. Interestingly, the overexpression of both miRs, alone or combined, slows down the cell cycle progression, modulates the p53 and HMGB1 expression and increases the sensitivity of cells to cisplatin, producing a marked impairment of cell proliferation and strengthening the apoptotic effect of the drug. However, the co-overexpression of the two miRs results more effective only in the regulation of the cell cycle, but does not enhance the sensitivity of MPM cells to cisplatin. Consequently, although the potential of miR-16 and miR-34a is confirmed, we must conclude that their combination does not improve the response of MPM to chemotherapy.

Se analiza la evidencia sobre el uso y efecto de técnicas de marketing, rotulado frontal y facultativo, así como perfil nutricional en envases de alimentos en las preferencias y consumo en niños, niñas y adolescentes con el objetivo de demostrar la ineficiencia de la normativa. Se realiza una revisión narrativa que incluye publicaciones dentro del periodo 2006-2016, las cuales se encuentran indexadas en Medline, EBSCO o Bireme. Se analizaron 37 trabajos completos. De acuerdo con lo anterior, 65% evaluó las diferentes técnicas de marketing, donde resultó dominante el uso de personajes, de declaraciones nutricionales y de salud y también se cuestionó su uso en productos no saludables. Se precisa el implemento de mecanismos eficaces de restricción de prácticas de marketing engañosas junto con un etiquetado que asegure el derecho a una información clara y veraz.

Edamame is a food-grade soybean that is harvested at the green-immature stage (R6) and sold fresh or frozen for consumption after steaming or boiling. Limited studies have been conducted on high-temperature sterilization of edamame in cans and on acid preservation of edamame. The objectives of this study were to evaluate the color retention and texture of edamame when pasteurized in acidic brine as compared to boiling, to assess the effect of sucrose and turmeric addition on acid-treated edamame, and to characterize varietal differences when edamame lines were pasteurized in an acidic brine at either R6 or R8 stage. All studies were conducted using industry-standard processing conditions for acid-preservation of food in glass containers. The results of this research indicated that acid processing caused losses in intensity of green color and hue, but much smaller than those reported when heat-processing edamame in cans. We also observed a small and borderline significant increase in texture (p = 0.0790) in acid-preserved samples. In addition, we found that green color is positively affected by the addition of turmeric to the brine, but not of sucrose. Finally, the varieties R07-589 (red-brown seed coat) and R09-345 (black seed coat) acid-processed at R8 had color and texture similar to canned in-kind substitute products. In conclusion, acid-preservation, and addition of turmeric to immature edamame, helped maintain an acceptable quality of the processed products.

Objetivo: Describir las características del uso del asistente mecánico de la tos (AMT) en el domicilio en niños/as con enfermedades neuromusculares (ENM) en seguimiento en nuestro hospital. Materiales y método: Estudio observacional, descriptivo, transversal y retrospectivo. Se incluyeron todos los sujetos pediátricos con ENM con AMT domiciliario con un uso del mismo no menor a seis meses, entre el 1 de enero de 2018 y el 31 de abril de 2019. Resultados: Fueron incluidos 59 sujetos, con una media de edad en años de 8,84 (± 4,01). El diagnóstico más frecuente fue Atrofia Muscular Espinal (AME) tipo II en 32 casos (54,2%). La mediana de edad al inicio del uso del AMT fue de 4 años (RIQ 3-7). El principal motivo de su indicación fueron las intercurrencias respiratorias a repetición. El equipo más utilizado fue el Philips Respironics E70® , en modo automático, con presiones de 40 cmH2O positiva y negativa, y la interfase más frecuente, la máscara oronasal. No se reportaron complicaciones. Conclusión: El diagnóstico más prevalente de los sujetos pediátricos con uso domiciliario del AMT fue AME, y el mismo se indicó mayormente por cuadros respiratorios a repetición. Los principales usuarios fueron los padres/ madres, en modo automático y con presiones de ±40 cmH2O.

El envejecimiento de la población es uno de los retos demográficos más importantes a los que se enfrenta el Estado argentino y la región que, sumado a otros cambios sociales estructurales, determinan un fuerte crecimiento de la institucionalización de las personas mayores. Pese a que Argentina ha suscripto a tratados de derechos humanos que gozan, incluso, de jerarquía constitucional y jerarquía superior a las leyes, la normativa local en la provincia de Córdoba, no garantiza una adecuada protección a los derechos humanos de las personas que habitan en residencias de larga estadía. En este sentido, la ratificación por parte del Estado argentino de la Convención Interamericana sobre la Protección de los Derechos Humanos de las Personas Mayores y su incorporación dentro del sistema normativo vigente obliga, de manera expresa, al Estado a adoptar medidas afirmativas y a realizar los ajustes necesarios para el ejercicio y cumplimiento de tales derechos, desde un nuevo paradigma

In order to study alternatives at the tissue biopsy to study EGFR status in NSCLC patients, we evaluated three different liquid biopsy platforms (plasma, urine and exhaled breath condensate, EBC). We also reviewed the literature of the cfDNA biological sources other than plasma and compared our results with it about the sensitivity to EGFR mutation determination. Twenty-two EGFR T790M-mutated NSCLC patients in progression to first-line treatment were enrolled and candidate to osimertinib. Plasma, urine and EBC samples were collected at baseline and every two months until progression. Molecular analysis of cfDNA was performed by ddPCR and compared to tissue results. At progression NGS analysis was performed. The EGFR activating mutation detection reached a sensitivity of 58 and 11% and for the T790M mutation of 45 and 10%, in plasma and urine samples, respectively. Any DNA content was recovered from EBC samples. Considering the plasma monitoring study, the worst survival was associated with positive shedding status; both plasma and urine molecular progression anticipated the radiological worsening. Our results confirmed the role of plasma liquid biopsy in testing EGFR mutational status, but unfortunately, did not evidence any improvement from the combination with alternative sources, as urine and EBC.

Overweight and obesity are great public health concerns, with an increasingly growing prevalence in both developed and developing countries. A primary cause of these issues is the globally increased consumption of food containing high calorie levels along with excessive fat, salt and sugar contents; preferences strongly linked to food industry marketing strategies and advertising. The development of clear and simple nutrition labeling, such as front-of-package labeling, is a useful tool to promote further well-informed consumer decisions. Yet, attempts to move forward with national public policies in this subject are often deterred due to front packaging labelling not being explicitly mentioned in nutrition labelling Codex Alimentarius regulation standards, which currently serves as the only framework proposed in this area. This work is particularly aimed at analyzing how front-of-package labeling omission in the Codex’s rules affects processes carried out in States that intend to implement this policy and, on this basis, to reflect on to what extent the Codex’s normative has the capacity to meet a growing need for food regulation in order to limit the impact of obesity. In order to do so, a normative analysis will be carried out: Codex regulatory documents on nutrition labeling will be reviewed, in line with The Technical Barriers to Trade Agreement; recommendations of relevant institutions in this field such as WHO and PAHO will also be revised; and, last, the Chilean experience front-of-package labeling implementation will be mentioned in order to illustrate obstacles that need to be addressed whenever a State intends this regulation’s implementation.

El presente artículo plantea la conexión existente entre el régimen protectorio del derecho a la salud, los derechos de los niños, niñas y adolescentes, y el régimen del Consumidor. En Argentina, la protección a la salud dentro de las relaciones de consumo es una prioridad, así, pues, el resguardo de los intereses económicos del “consumidor”, como su salud tienen jerarquía constitucional. El carácter tuitivo se justifica en la asimetría que caracteriza a la “relación de consumo”; situación que se agrava cuando personas que ya son vulnerables forman parte de ella. Lo expresado cobra mayor relevancia al analizar la publicidad dirigida al público infantil, específicamente la de alimentos no saludables. Esto último, ha sido limitado en varios países y ha sido objeto de pronunciamientos judiciales en Latinoamérica. Realizando la interpretación de todo el ordenamiento jurídico se pueden ofrecer razones para prohibir la publicidad de alimentos no saludables dirigida a un público infantil. This article analyzes the connection between the regulations to the right to health, the right of children and adolescents and consumer`s regime. The protection to the health within the norms that regulate the consumption is a priority. In Argentina the protection of the economic interests of the "consumer", as well as, his/her health has a constitutional hierarchy. The tuitive character is justified by the asymmetry that is intrinsic to the "consumption relationship". This is even worse when people who are already vulnerable are involved in this relationship. This becomes more relevant when children`s advertising is analyzed, specifically unhealthy food advertising. This has been limited in several countries and has been subjected to judicial pronouncements in Latin America. By making an adequate interpretation of the entire legal system, good reasons can be offered to prohibit the advertising of unhealthy food addressed to a child audience.

Synaptic dysfunction and loss caused by age-dependent accumulation of synaptotoxic beta amyloid (Abeta) 1-42 oligomers is proposed to underlie cognitive decline in Alzheimer's disease (AD). Alterations in membrane trafficking induced by Abeta oligomers mediates reduction in neuronal surface receptor expression that is the basis for inhibition of electrophysiological measures of synaptic plasticity and thus learning and memory. We have utilized phenotypic screens in mature, in vitro cultures of rat brain cells to identify small molecules which block or prevent the binding and effects of Abeta oligomers. Synthetic Abeta oligomers bind saturably to a single site on neuronal synapses and induce deficits in membrane trafficking in neuronal cultures with an EC50 that corresponds to its binding affinity. The therapeutic lead compounds we have found are pharmacological antagonists of Abeta oligomers, reducing the binding of Abeta oligomers to neurons in vitro, preventing spine loss in neurons and preventing and treating oligomer-induced deficits in membrane trafficking. These molecules are highly brain penetrant and prevent and restore cognitive deficits in mouse models of Alzheimer's disease. Counter-screening these compounds against a broad panel of potential CNS targets revealed they are highly potent and specific ligands of the sigma-2/PGRMC1 receptor. Brain concentrations of the compounds corresponding to greater than 80% receptor occupancy at the sigma-2/PGRMC1 receptor restore cognitive function in transgenic hAPP Swe/Ldn mice. These studies demonstrate that synthetic and human-derived Abeta oligomers act as pharmacologically-behaved ligands at neuronal receptors--i.e. they exhibit saturable binding to a target, they exert a functional effect related to their binding and their displacement by small molecule antagonists blocks their functional effect. The first-in-class small molecule receptor antagonists described here restore memory to normal in multiple AD models and sustain improvement long-term, representing a novel mechanism of action for disease-modifying Alzheimer's therapeutics.

This study was aimed at: (i) investigating the expression profiles of some antioxidant and epidermal growth factor receptor genes in cancerous and unaffected tissues of patients undergoing lung resection for non-small cell lung cancer (NSCLC) (cross-sectional phase), (ii) evaluating if gene expression levels at the time of surgery may be associated to patients' survival (prospective phase). Antioxidant genes included heme oxygenase 1 (HO-1), superoxide dismutase-1 (SOD-1), and -2 (SOD-2), whereas epidermal growth factor receptor genes consisted of epidermal growth factor receptor (EGFR) and v-erb-b2 erythroblastic leukaemia viral oncogene homolog 2 (HER-2). Twenty-eight couples of lung biopsies were obtained and gene transcripts were quantified by Real Time RT-PCR. The average follow-up of patients lasted about 60 months. In the cancerous tissues, antioxidant genes were significantly hypo-expressed than in unaffected tissues. The HER-2 transcript levels prevailed in adenocarcinomas, whereas EGFR in squamocellular carcinomas. Patients overexpressing HER-2 in the cancerous tissues showed significantly lower 5-year survival than the others.