Estradiol and progesterone regulate proliferation and apoptosis in colon cancer

Epidemiological studies describe estrogens as protectors in the development of colon cancer in postmenopausal women treated with hormone replacement therapy. However, the role of progesterone in colon cancer has been minimally studied and the results are controversial. For the above, the objective of this work was to determine the hormonal regulation exerted by natural ovarian steroids on proliferation and apoptosis in an experimental model of colon cancer in ovariectomized rats treated with 17-beta estradiol and progesterone. Sprague–Dawley rats were exposed to the carcinogen 1,2-dimethylhydrazine to induce colon tumors. Thirty days later, the rats were ovariectomized and treated with estradiol (60 μg/kg), progesterone (10 mg/kg), estradiol plus progesterone (60 μg/kg and 10 mg/kg) or vehicle. We observed no significant differences in colon cancer incidence and tumor multiplicity between the groups. Nevertheless, we observed a decrease in PCNA expression and a greater number of apoptotic index, higher expression of caspase 3, cleaved PARP and cleaved caspase 8 in tumors, confirming the activation of the extrinsic pathway of apoptosis by the combined treatment. In addition, we observed a higher expression of estrogen receptor beta in these tumors. We conclude that the action of both hormones, estradiol and progesterone, is necessary to reduce proliferation and increase apoptosis in colon tumors, probably through estrogen receptor beta activation.Fil: Sasso, Corina Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Santiano, Flavia Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Campo Verde Arbocco, Fiorella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Zyla, Leila Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Semino, Silvana Noemí. Universidad Nacional de Cuyo. Hospital Universitario; ArgentinaFil: Guerrero Gimenez, Martin Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Pistone Creydt, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: López Fontana, Constanza Matilde. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Caron, Ruben Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

Changes in prolactin receptor location in prostate tumors

Introduction: Prolactin (PRL) binds its receptor (PRLR) and stimulates cell proliferation, differentiation and survival in prostate cancer (PCa) cell lines via STAT5a, MAPK and AKT. Objective: To evaluate the expression of PRL and PRLR in normal and tumor prostate tissues with different Gleason patterns. Methods: Samples of normal, benign prostatic hyperplasia and PCa with different Gleason patterns were selected from radical prostatectomy. The intensity, location and percentage of stained cells for PRL and PRLR were evaluated by Immunohistochemistry. Co-localization was observed by confocal microscopy. Results: PRL was expressed diffusely and with a mild intensity in the cytoplasm of normal and tumor prostate luminal cells. Its expression only augmented in the Gleason 3 pattern (p 0.0001). The immunostaining intensity and the percentage of positive cells for PRLR did not vary between normal and tumor tissues. However, the location of the PRLR was modified by the tumorigenic process. In non-tumor tissues, PRLR expression was mostly in plasma membrane in the apical zone of epithelial cells. In tumor tissues, it was expressed in intracellular vesicles. The co-localization of PRL and PRLR was demonstrated in normal and tumor tissues suggesting that PRL could be acting in an autocrine and paracrine manner. Conclusion: PRL and its receptor were present in the cytoplasm of the epithelial cells of the normal and tumor prostate gland. In tumor tissues, the change in the location and appearance of cryptic PRLRs that store PRL may keep active the different signaling pathways related to cell proliferation and survival.Fil: López Fontana, Gastón. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Clinica Andina de Urología; ArgentinaFil: Rey Echalecu, Lara Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Santiano, Flavia Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: López Fontana, José Rodrigo. Clinica Andina de Urología; ArgentinaFil: López Laur, José Daniel. Clinica Andina de Urología; ArgentinaFil: Zyla, Leila Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Valdemoros, Paula. Laboratorio de Anatomía Patológica Vega Valdemoros; ArgentinaFil: Guerrero Gimenez, Martin Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Fernandez Muñoz, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Gomez, Silvina Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Bruna, Flavia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Guglielmi, Juan Manuel. Clinica Andina de Urología; ArgentinaFil: Caron, Ruben Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: López Fontana, Constanza Matilde. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

Chagoma as brain mass lesion

La enfermedad de Chagas es una zoonosis parasitaria, endémica en América Latina, causada por el protozoo Trypanosoma cruzi. En el sistema nervioso central de humanos existen dos presentaciones de la enfermedad: meningoencefalitis difusa que suele coincidir con la observación de tripomastigotes en líquido cefalorraquídeo o chagoma que consiste en nidos de amastigotes asociados a encefalitis necrotizante multifocal con abscesos. Se presenta el caso de un paciente fumador y drogadicto que ingresa al hospital por cuadro convulsivo, hemianopsia homónima, paresia facial y anestesia en hemicuerpo izquierdo. Se realiza una resonancia magnética nuclear, donde se observa masa ocupante de espacio en la zona parietal derecha subcortical. En el examen directo de la biopsia, se detecta la presencia de tripomastigotes móviles y en la coloración de Giemsa, amastigotes intracelulares de T. cruzi. Luego de la anamnesis del paciente se solicitan estudios serológicos y detección de anticuepos para el virus de la inmunodeficiencia adquirida (VIH) por Elisa, resultando positiva. La enfermedad de Chagas es una de las patologías oportunistas que debe considerarse en los diagnósticos diferenciales de lesiones ocupantes de espacio en el sistema nervioso central dado que su rápido diagnóstico y tratamiento oportuno conllevan a una mejor sobrevida del paciente.Chagas disease is a parasitic zoonosis, endemic to Latin America, caused by the protozoan Trypanosoma cruzi. In the human central nervous system, there are two presentations of the disease: meningoencephalitis with trypomastigotes in cephalo raquidean fluid or chagoma, that consists of a nest of amastigotes associated with multifocal necrotizing encephalitis with abscesses. We present the case of a smoker patient and, a user of illicit drugs, who was admitted to the hospital due to convulsive condition, left homonymous hemianopsia, left facial paresis and, left lower body anesthesia. A nuclear magnetic resonance was performed, where space occupant mass was observed in the subcortical right parietal area. Mobile trypomastigots were detected by direct examination of the biopsy and intracellular amastigotes of T. cruzi by Giemsa staining. After the patient’s anamnesis, serological studies and detection of anti-HIV antibodies by Elisa were requested, being positive. Chagas disease is one of the opportunistic pathologies to be considered in the differential diagnoses of occupant lesions of central nervous system space since its rapid diagnosis and timely treatment lead to better patient survival.Asociación Parasitológica Argentin

Risk factors associated with cusp fractures in posterior permanent teeth—a cross-sectional study

Objectives: This cross-sectional study aimed to evaluate the frequency and risk factors associated with cusp fractures in posterior permanent teeth. Methods: Patients presented cusp fractures on posterior permanent teeth, clinically assessed in up to 7 days after the event, and requesting dental treatment at two public services were included in this cross-sectional study. Fractured teeth already treated, with antagonist absence, or with prosthesis (total or removable) were excluded. Demographic and clinical data were collected to draw the patient profiles and establish how teeth were affected individually. Statistical analysis was performed by the Fisher exact test, and uni- and multivariate logistic regression (α = 0.05). Results: One hundred and seventy-seven (177) patients from 16 to 66 years old (±41.56), from 1998 to 2016, were included in this study. Non-functional and lingual cusps presented a higher fracture than functional and buccal cusps, respectively. Fractures were more common in teeth with isthmus wider than 1/3 of the intercuspid distance and/or more than three restored surfaces. Teeth with endodontic treatment presented a higher subgingival fracture. On lingual cusps, fracture type and location were significantly associated, being that total fractures were 3.2 times more likely to occur than partial fractures, and subgingival were 3.62 times more likely to occur than supragingival fractures. Conclusion: Indications of classic protection on functional cusps (LUBL) was refuted since, generally, nonfunctional cusps fractured more than the functional cusps. However, upper pre-molars showed more fractures in functional cusps and lower molars presented more fractures on the nonfunctional cusps. In general, lingual cusps were the most fractured and were associated with a higher prevalence of severe fractures (total fractures at the subgingival level). Fractures were more common in teeth where the restoration had an isthmus wider than 1/3 of the intercuspid distance and/or involved more than three restored surfaces. Most of the patients did not show previous symptoms and signs. Overall, teeth with endodontic treatment presented a higher subgingival fracture

SPINK7 expression changes accompanied by HER2, P53 and RB1 can be relevant in predicting oral squamous cell carcinoma at a molecular level

The oral squamous cell carcinoma (OSCC), which has a high morbidity rate, affects patients worldwide. Changes in SPINK7 in precancerous lesions could promote oncogenesis. Our aim was to evaluate SPINK7 as a potential molecular biomarker which predicts OSCC stages, compared to: HER2, TP53, RB1, NFKB and CYP4B1. This study used oral biopsies from three patient groups: dysplasia (n = 33), less invasive (n = 28) and highly invasive OSCC (n = 18). The control group consisted of clinically suspicious cases later to be confirmed as normal mucosa (n = 20). Gene levels of SPINK7, P53, RB, NFKB and CYP4B1 were quantified by qPCR. SPINK7 levels were correlated with a cohort of 330 patients from the TCGA. Also, SPINK7, HER2, TP53, and RB1, were evaluated by immunohistofluorescence. One-way Kruskal–Wallis test and Dunn's post-hoc with a p < 0.05 significance was used to analyze data. In OSCC, the SPINK7 expression had down regulated while P53, RB, NFKB and CYP4B1 had up regulated (p < 0.001). SPINK7 had also diminished in TCGA patients (p = 2.10e-6). In less invasive OSCC, SPINK7 and HER2 proteins had decreased while TP53 and RB1 had increased with respect to the other groups (p < 0.05). The changes of SPINK7 accompanied by HER2, P53 and RB1 can be used to classify the molecular stage of OSCC lesions allowing a diagnosis at molecular and histopathological levels.Fil: Pennacchiotti, Graciela Laura. Universidad de Chile; ChileFil: Valdes Garrido, Fabio. Instituto Nacional del Cáncer; ChileFil: González Arriaga, Wilfredo Alejandro. Universidad de Valparaíso; ChileFil: Montes, Héctor Federico. Universidad Nacional de Cuyo. Facultad de Odontologia; ArgentinaFil: Parra, Judith Maria Roxana. Universidad Nacional de Cuyo. Facultad de Odontologia; ArgentinaFil: Guida, Valeria Andrea. Universidad Nacional de Cuyo. Facultad de Odontologia; ArgentinaFil: Gomez, Silvina Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Guerrero Gimenez, Martin Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Fernandez Muñoz, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Zoppino, Felipe Carlos Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Caron, Ruben Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ezquer, Marcelo Eduardo. Universidad del Desarrollo; ChileFil: Ramires Fernández, Ricardo. Universidad Mayor; ChileFil: Bruna, Flavia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Odontologia; Argentin

Soil fertility and drought interact to determine large variations in wood production for a hyperdominant Amazonian tree species

Introduction: The productivity of the Amazon Rainforest is related to climate and soil fertility. However, the degrees to which these interactions influence multiannual to decadal variations in tree diameter growth are still poorly explored. Methods: To fill this gap, we used radiocarbon measurements to evaluate the variation in tree growth rates over the past decades in an important hyperdominant species, Eschweilera coriacea (Lecythidaceae), from six sites in the Brazilian Amazon that span a range of soil properties and climate. Results: Using linear mixed-effects models, we show that temporal variations in mean annual diameter increment evaluated over a specific time period reflect interactions between soil fertility and the drought index (SPEI-Standardized Precipitation and Evapotranspiration Index). Discussion: Our results indicate that the growth response of trees to drought is strongly dependent on soil conditions, a facet of forest productivity that is still underexplored, and which has great potential for improving predictions of future tropical tree growth in the face of projected climate change

COVID-19 IDD: A global survey exploring the impact of COVID-19 on individuals with intellectual and developmental disabilities and their caregivers

Background: This protocol outlines research to explore the impact of coronavirus disease 2019 (COVID-19) on individuals who have intellectual and developmental disabilities and their caregivers. Evidence suggests that people with intellectual and developmental disabilities experience disparities in healthcare access and utilisation. This disparity was evident early in the pandemic when discussions arose regarding the potential exclusion of this population to critical care. Methods: An anonymous online survey will be conducted with caregivers, both family members and paid staff, to explore the impact of COVID-19 on this population in terms of demographics, living arrangements, access to services, the impact of social distancing, and also carer wellbeing. The survey will be developed by the research team, many of whom are experts in intellectual disability within their own jurisdictions. Using back-translation our team will translate the survey for distribution in 16 countries worldwide for international comparison. The survey team have extensive personal and professional networks in intellectual disability and will promote the survey widely on social media with the support of local disability and advocacy agencies. Statistical descriptive and comparative analyses will be conducted. Ethical approval has been obtained for this study from University College Dublin’s Human Research Ethics Committee (HS-20-28-Linehan). Dissemination: Study findings will be prepared in a number of formats in order to meet the needs of different audiences. Outputs will include academic papers, lessons learned paper, practice guidelines, reports, infographics and video content. These outputs will be directed to families, frontline and management delivering disability services, national-level policy makers, healthcare quality and delivery authorities, national pandemic organisations and international bodies

Growth of Fungal Cells and the Production of Mycotoxins

Some filamentous fungi are able to grow in food and produce toxic metabolites. It occurs mainly in grains, cereals, oilseeds and some by-products. The growth of fungi in a particular food is governed largely by a series of physical and chemical parameters. The production of toxic metabolites is not confined to a single group of molds irrespective of whether they are grouped according to structure, ecology, or phylogenetic relationships. Mycotoxins can be carcinogenic and cause several harmful effects to both human and animal organisms, in addition to generating large economic losses. The major mycotoxins found in food are the aflatoxins, fumonisins, ochratoxins, patulin, zearalenone, and trichothecenes, generally stable at high temperatures and long storage periods. Considering the difficult prevention and control, international organizations for food safety establish safe levels of these toxins in food destined for both human and animal consumption. Good agricultural practices and control of temperature and moisture during storage are factors which contribute significantly to inhibit the production of mycotoxins. The use of some fungistatic products, such as essential oils and antioxidants, as well as physical, mechanical, chemical, or thermal processing, represents important methods to have the concentration of mycotoxins reduced in food

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure &lt;= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt