Transcriptional analysis of landmark molecular pathways in lung adenocarcinoma results in a clinically relevant classification with potential therapeutic implications.

Lung adenocarcinoma (LUAD) is a molecularly heterogeneous disease. In addition to genomic alterations, cancer transcriptional profiling can be helpful to tailor cancer treatment and to estimate each patient's outcome. Transcriptional activity levels of 50 molecular pathways were inferred in 4573 LUAD patients using Gene Set Variation Analysis (GSVA) method. Seven LUAD subtypes were defined and independently validated based on the combined behavior of the studied pathways: AD (adenocarcinoma subtype) 1-7. AD1, AD4, and AD5 subtypes were associated with better overall survival. AD1 and AD4 subtypes were enriched in epidermal growth factor receptor (EGFR) mutations, whereas AD2 and AD6 showed higher tumor protein p53 (TP53) alteration frequencies. AD2 and AD6 subtypes correlated with higher genome instability, proliferation-related pathway expression, and specific sensitivity to chemotherapy, based on data from LUAD cell lines. LUAD subtypes were able to predict immunotherapy response in addition to CD274 (PD-L1) gene expression and tumor mutational burden (TMB). AD2 and AD4 subtypes were associated with potential resistance and response to immunotherapy, respectively. Thus, analysis of transcriptomic data could improve patient stratification beyond genomics and single biomarkers (i.e., PD-L1 and TMB) and may lay the foundation for more personalized treatment avenues, especially in driver-negative LUAD.

Yolk corticosterone and progesterone levels in Greater Rhea (Rhea americana) eggs vary in a changing social environment.

Maternal hormones in avian egg yolks may signal and prepare offspring for the prevailing conditions. However, this adjustment requires some degree of flexibility in regulating yolk hormone deposition. The Greater Rhea (Rhea americana) has a particular mating system that combines mixed polygyny and polyandry, communal nesting, and exclusive paternal care of chicks. In this species, we previously found that yolk hormone deposition varies among eggs of different captive populations and could influence chicks' physiology and behavior. However, it is still unknown whether females can modify yolk hormone deposition in a changing social environment. Using a captive population of Greater Rheas, in this study, we quantified yolk hormone levels before and after a reduction in the number of females present in the population. We found that females deposited on average higher yolk corticosterone and lower yolk progesterone after the change in their social environment. Since corticosterone deposited into the yolk comes exclusively from the female's plasma, our results suggest that females had, on average, higher plasma corticosterone levels. The change in the number of females may increase the events of male-male competitions, courtships, and matings, leading to an increase of corticosterone in the females' plasma and then into their eggs. Since we previously found that higher yolk corticosterone and lower yolk progesterone were associated with the production of chicks that have an attenuated stress response, the present study results suggest that yolk hormone deposition is mediated by flexible mechanisms that could adjust development to the prevailing conditions.

Gene Expression Profiling as a Potential Tool for Precision Oncology in Non-Small Cell Lung Cancer.

Recent technological advances and the application of high-throughput mutation and transcriptome analyses have improved our understanding of cancer diseases, including non-small cell lung cancer. For instance, genomic profiling has allowed the identification of mutational events which can be treated with specific agents. However, detection of DNA alterations does not fully recapitulate the complexity of the disease and it does not allow selection of patients that benefit from chemo- or immunotherapy. In this context, transcriptional profiling has emerged as a promising tool for patient stratification and treatment guidance. For instance, transcriptional profiling has proven to be especially useful in the context of acquired resistance to targeted therapies and patients lacking targetable genomic alterations. Moreover, the comprehensive characterization of the expression level of the different pathways and genes involved in tumor progression is likely to better predict clinical benefit from different treatments than single biomarkers such as PD-L1 or tumor mutational burden in the case of immunotherapy. However, intrinsic technical and analytical limitations have hindered the use of these expression signatures in the clinical setting. In this review, we will focus on the data reported on molecular classification of non-small cell lung cancer and discuss the potential of transcriptional profiling as a predictor of survival and as a patient stratification tool to further personalize treatments.

Integrative transcriptome analysis of malignant pleural mesothelioma reveals a clinically relevant immune-based classification.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasia affecting the lung mesothelium. Immune checkpoint inhibitors (ICI) in MPM have not been extremely successful, likely due to poor identification of suitable candidate patients for the therapy. We aimed to identify cellular immune fractions associated with clinical outcome and classify patients with MPM based on their immune contexture. For each defined group, we sought for molecular specificities that could help further define our MPM classification at the genomic and transcriptomic level, as well as identify differential therapeutic strategies based on transcriptional signatures predictive of drug response. METHODS: The abundance of 20 immune cell fractions in 516 MPM samples from 7 gene expression datasets was inferred using gene set variation analysis. Identification of clinically relevant fractions was performed with Cox proportional-hazards models adjusted for age, stage, sex, and tumor histology. Immune-based groups were defined based on the identified fractions. RESULTS: T-helper 2 (TH2) and cytotoxic T (TC) cells were found to be consistently associated with overall survival. Three immune clusters (IG) were subsequently defined based on TH2 and TC immune infiltration levels: IG1 (54.5%) was characterized by high TH2 and low TC levels, IG2 (37%) had either low or high levels of both fractions, and IG3 (8.5%) was defined by low TH2 and high TC levels. IG1 and IG3 groups were associated with worse and better overall survival, respectively. While no differential genomic alterations were identified among immune groups, at the transcriptional level, IG1 samples showed upregulation of proliferation signatures, while IG3 samples presented upregulation of immune and inflammation-related pathways. Finally, the integration of gene expression with functional signatures of drug response showed that IG3 patients might be more likely to respond to ICI. CONCLUSIONS: This study identifies a novel immune-based signature with potential clinical relevance based on TH2 and TC levels, unveiling a fraction of patients with MPM with better prognosis and who might benefit from immune-based therapies. Molecular specificities of the different groups might be used to tailor specific potential therapies in the future.

Expression of aggressiveness modulates mesencephalic c-fos activation during a social interaction test in Japanese quail (Coturnix japonica).

It is well known that during a social conflict, interactions are dependent on the animal's propensity to behave aggressively as well as the behavior of the opponent. However, discriminating between these two confounding factors was difficult. Recently, a Social Interaction (SI) test using photocastrated males as non-aggressive stimuli was proposed as a useful tool to evaluate aggressiveness. The avian Intercollicular- Griseum centralis complex (comparable to mammalian periaqueductal gray) has been reported as a crucial node in the descending pathways that organize behavioral and autonomic aspects of defensive responses and aggressiveness. Herein, using the SI test, we evaluated whether mesencephalic areas are activated (expressed c-fos) when photostimulated adult males are confronted with non-responsive (non-aggressive) opponents. Furthermore, we also examined whether mesencephalic activation is related to male performance during the SI test (i.e., aggressive vs. non-aggressive males) in birds reared in enriched or in standard environments. Five mesencephalic areas at two anatomic levels (intermediate and rostral) and locomotion during SI testing were studied. Aggressive males showed increased c-fos expression in all areas studied, and moved at faster speeds in comparison to their non-aggressive and control counterparts. Non-aggressive males and the test controls showed similar c-fos labeling. In general, rearing condition did not appear to influence c-fos expression nor behavior during the SI test. Findings suggest that mesencephalic activation is involved when males are actively expressing aggressive behaviors. This overall phenomenon is shown regardless of both the environmental stimuli provided during the birds´ rearing and the potentially stressful stimuli during the SI trial.

Insights into thermal stress in Japanese quail (Coturnix coturnix): dynamics of immunoendocrine and biochemical responses during and after chronic exposure.

Avian require comfortable temperatures for optimal development and heat stress is a high concern in warm weather countries. We aimed to assess the dynamics of immunoendocrine and biochemical variables responses of birds exposed to a heat stressor applied during daylight hours, during the chronic stress and the recovery periods. We hypothesize that variables involved in the birds response will be differentially and gradually modified during those periods. Female quail (n = 210) were housed in six rearing boxes. At 29 days of age, the temperature in three boxes was increased from 24 to 34 °C during the light period throughout the nine days (Stress Treatment). The other three boxes remained at 24 °C and were used as controls. The subsequent 12 days were considered as recovery period. Different sets of 12 birds/treatment were blood-sampled at 29 (basal), 32, 35, 38 (stress), 41, 44, 47, and 50 (recovery) days of age, respectively. Immunoendocrine (corticosterone, lymphoproliferation, heterophil/lymphocyte ratio (H/L), and antibody response) and biochemical (glucose, total proteins, globulins, and albumin) variables were assessed. During stress, progressive corticosterone and H/L increments, and antibody titers and lymphoproliferation decreases were detected. No clear pattern of changes was found in biochemical variables. During recovery, while corticosterone and lymphoproliferation had recovered three days after the stressor ended, H/L and antibody responses required respectively nine and 12 days to recover to their basal levels, respectively. Findings suggest that immunity is already threatened when heat stress is sustained for three or more days. However, the system appears resilient, needing six to 12 days to recover to their basal responses.

Distribution and concentration of maternal progesterone in the yolk of Greater Rhea eggs (Rhea americana).

Progesterone is the most concentrated maternal yolk steroid characterized to date in birds; however, no information about it is available in ratite eggs. We collected freshly laid eggs from zoo-housed Greater Rhea females (Rhea americana) bred under similar rearing conditions during two breeding seasons to characterize concentration and distribution of maternal yolk progesterone. After high-performance liquid chromatography analysis, yolk hormone was measured using a commercial electrochemiluminescence immunoassay. Progesterone concentrations were found to vary significantly among the yolk layers, supporting a follicular origin for this steroid in Greater Rhea eggs. Additionally, highly similar mean absolute yolk progesterone concentrations were detected between 2013 and 2015 breeding seasons (1,332.98 ± 82.59 and 1,313.59 ± 85.19 ng/g, respectively). These values are also comparable to those found in some domestic carinate species. Findings suggest that at population level, when rearing conditions are similar, mean absolute yolk maternal progesterone concentrations also appear bounded. Future research on the factors and mechanisms that regulate progesterone deposition in Greater Rhea eggs is needed to better understand whether its levels depend on different rearing conditions.

Immune neuroendocrine phenotypes in Coturnix coturnix: do avian species show LEWIS/FISCHER-like profiles?

Immunoneuroendocrinology studies have identified conserved communicational paths in birds and mammals, e.g. the Hypothalamus-Pituitary-Adrenal axis with anti-inflammatory activity mediated by glucocorticoids. Immune neuroendocrine phenotypes (INPs) have been proposed for mammals implying the categorization of a population in subgroups underlying divergent immune-neuroendocrine interactions. These phenotypes were studied in the context of the LEWIS/FISCHER paradigm (rats expressing high or low pro-inflammatory profiles, respectively). Although avian species have some common immunological mechanisms with mammals, they have also evolved some distinct strategies and, until now, it has not been studied whether birds may also share with mammals similar INPs. Based on corticosterone levels we determined the existence of two divergent groups in Coturnix coturnix that also differed in other immune-neuroendocrine responses. Quail with lowest corticosterone showed higher lymphoproliferative and antibody responses, interferon-γ and interleukin-1ß mRNA expression levels and lower frequencies of leukocyte subpopulations distribution and interleukin-13 levels, than their higher corticosterone counterparts. Results suggest the existence of INPs in birds, comparable to mammalian LEWIS/FISCHER profiles, where basal corticosterone also underlies responses of comparable variables associated to the phenotypes. Concluding, INP may not be a mammalian distinct feature, leading to discuss whether these profiles represent a parallel phenomenon evolved in birds and mammals, or a common feature inherited from a reptilian ancestor millions of years ago.

[Evaluation of the impact of a control program against taeniasis-cysticercosis (Taenia solium)]. / Evaluación del impacto de un programa de control de la teniasis-cisticercosis (Taenia solium).

OBJETIVE: The impact of a control program is evaluated to eventually eradicate taeniasis-cysticercosis (Taenia solium) based on education and vaccination of pigs. MATERIALS AND METHODS: The prevalence of porcine cysticercosis was estimated using tongue inspection, ultrasound and determination of antibodies, before and three years after the application in three regions of the state of Guerrero. RESULTS: A significant reduction in the prevalence of porcine cysticercosis of 7 to 0.5% and 3.6 to 0.3% estimated by tongue examination or ultrasound respectively (p<0.01) and a no significant decrease in seroprevalence from 17.7 to 13.3% were observed. CONCLUSIONS: The reduction of the prevalence of taeniasis-cysticercosis establishes the program's effectiveness in preventing infection. The sustained presence of antibodies, compatible with contact of Taenia solium or other related helminths, underlines the importance of maintaining interventions to achieve eradication.

Evaluación del impacto de un programa de control de la teniasis-cisticercosis (Taenia solium) / Evaluation of the impact of a control program against taeniasis-cysticercosis (Taenia solium)

Objetivo. Evaluar el impacto de un programa de control de la teniasis-cisticercosis por Taenia solium con fines de erradicación, basado en educación de la comunidad y vacunación de cerdos. Material y métodos. Se estimó la prevalencia de cisticercosis porcina por medio de la palpación de lengua, ultrasonido y presencia de anticuerpos en suero, antes de iniciar el programa y tres años después, en tres regiones del estado de Guerrero. Resultados. Se observó una reducción significativa en la prevalencia de cisticercosis porcina de 7 a 0.5% y de 3.6 a 0.3%, estimadas por examen de lengua y ultrasonido, respectivamente (p<0.01), y una disminución no significativa de la seroprevalencia de 17.7 a 13.3%. Conclusiones. La reducción de la prevalencia de teniasis-cisticercosis comprueba la efectividad del programa para prevenir la infección. La presencia sostenida de anticuerpos es compatible con continuos contactos con Taenia solium u otros helmintos relacionados, y señala la necesidad de mantener las intervenciones para lograr su erradicación.

Objetive. The impact of a control program is evaluated to eventually eradicate taeniasis-cysticercosis (Taenia solium) based on education and vaccination of pigs. Materials and methods. The prevalence of porcine cysticercosis was estimated using tongue inspection, ultrasound and determination of antibodies, before and three years after the application in three regions of the state of Guerrero. Results. A significant reduction in the prevalence of porcine cysticercosis of 7 to 0.5% and 3.6 to 0.3% estimated by tongue examination or ultrasound respectively (p<0.01) and a no significant decrease in seroprevalence from 17.7 to 13.3% were observed. Conclusions. The reduction of the prevalence of taeniasis-cysticercosis establishes the program's effectiveness in preventing infection. The sustained presence of antibodies, compatible with contact of Taenia solium or other related helminths, underlines the importance of maintaining interventions to achieve eradication.

Relevamiento serológico de anticuerpos contra enfermedades virales de interés sanitario en llamas (Lama glama) de la provincia de Jujuy, Argentina / Serological survey of antibodies aainst vital diseases of public health interest in llamas (Lama glama) from Jujuy rpovince, Argentina

Las poblaciones de llamas de Argentina se concentran principalmente en la provincia de Jujuy; su explotación representa un importante recurso económico de las comunidades altoandinas. El objetivo de este trabajo fue evaluar la seroprevalencia de anticuerpos contra algunos agentes virales asociados a enfermedades de impacto productivo en rodeos de llamas de Jujuy. Se analizaron 349 sueros de llamas adultas de 6 departamentos de la puna jujeña ubicados por encima de los 3300 msnm. Se obtuvo una prevalencia del 100 % para rotavirus grupo A y del 70 % para el virus parainfluenza-3 bovino, mientras que no se detectaron reactores para herpesvirus bovino 1, virus de la diarrea viral bovina, influenza A humana (H1N1) e influenza equina (H3N8). Los resultados obtenidos confirman la amplia distribución de rotavirus y virus parainfluenza y la baja susceptibilidad a herpesvirus y pestivirus en las tropas de llamas de la puna jujeña

Llama population from Argentina is mainly concentrated in the Andean Puna, Jujuy. Llamas represent an important economic resource for the Andean communities. The aim of this study was to investigate the prevalence of antibodies against viral antigens associated to viral diseases of economic impact (neonatal diarrhea, reproductive and respiratory syndromes). A total of 349 serum samples from adult llamas were analyzed. The obtained antibody prevalence was 100 % for Rotavirus A and 70 % for Bovine parainfluenza virus 3. In contrast, no reactors were detected to Bovine herpesvirus 1, Bovine viral diarrhea virus 1, Human influenza A virus (H1N1) and Equine influenza virus (H3N8). These results confirm the wide circulation of rotavirus and parainfluenza virus in Argentinean llamas and suggest that susceptibility to infection with bovine herpesvirus, pestivirus and influenza A viruses is low. This serologic survey provides novel information regarding the epidemiology of viral diseases affecting llamas from the Argentinean Andean Puna

Aplicación de Laserterapia en la hiperestesia dentinal / Application of laser therapy for the treatment of dentinal hyperesthesia

Se realizó un estudio experimental para evaluar la eficacia del láser de baja potencia combinada con barniz de flúor al 2 por ciento (Profilac) en el tratamiento de la Hiperestesia Dentinaria en pacientes atendidos en la Clínica Estomatológíca de Ciro Redondo en el periodo en el Octubre del 2007 a Enero del 2008. El universo de estudio estuvo constituido por 75 pacientes diagnosticados con hiperestesia dentinal en el periodo de tiempo antes mencionado, quedando conformada la muestra por aquellos 25 que cumplieron con los criterios preestablecidos para el estudio. Con la aplicación del láser combinado con Laca Flúor (Profilac), se observó una remisión del dolor que aumentó paulatinamente con las sesiones de tratamiento lográndose eliminar en casi la totalidad de los casos la sintomatología al finalizar el mismo, evaluándose el tratamiento de eficaz en el 100 por ciento de los casos. Solamente se encontró una recidiva al año de tratamiento.

An experimental study was carried out, to evaluate the effectiveness of the low - power laser combined with fluoride varnish to 2 percent Profilac in the treatment of the Dentinal Hyperesthesia in patients attended to in the Estomatology Clinic of Ciro Redondo in the period from October 2007 to January 2008. The universe of study was constituted by 75 patients diagnosed with dentinal hyperesthesia in the period of time indicated above, being conformed the sample by those 25 who fulfilled the pre-established criteria for the study. With the application of the laser combined with Lacquer Fluorine Profilac, a remission of the pain was observed that increased gradually with the treatment sessions, having been obtained to almost eliminate in the totality of the cases the group of symptoms when finalizing it, evaluating the treatment of effective in 100 percent of the cases. We only found a recidive after a year of treatment.