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BACKGROUND: Deeper insights into ERBB2-driven cancers are essential to develop new treatment approaches for ERBB2+ breast cancers (BCs). We employed the Collaborative Cross (CC) mouse model to unearth genetic factors underpinning Erbb2-driven mammary tumour development and metastasis. METHODS: 732 F1 hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains were monitored for mammary tumour phenotypes. GWAS pinpointed SNPs that influence various tumour phenotypes. Multivariate analyses and models were used to construct the polygenic score and to develop a mouse tumour susceptibility gene signature (mTSGS), where the corresponding human ortholog was identified and designated as hTSGS. The importance and clinical value of hTSGS in human BC was evaluated using public datasets, encompassing TCGA, METABRIC, GSE96058, and I-SPY2 cohorts. The predictive power of mTSGS for response to chemotherapy was validated in vivo using genetically diverse MMTV-Erbb2 mice. FINDINGS: Distinct variances in tumour onset, multiplicity, and metastatic patterns were observed in F1-hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains. Besides lung metastasis, liver and kidney metastases emerged in specific CC strains. GWAS identified specific SNPs significantly associated with tumour onset, multiplicity, lung metastasis, and liver metastasis. Multivariate analyses flagged SNPs in 20 genes (Stx6, Ramp1, Traf3ip1, Nckap5, Pfkfb2, Trmt1l, Rprd1b, Rer1, Sepsecs, Rhobtb1, Tsen15, Abcc3, Arid5b, Tnr, Dock2, Tti1, Fam81a, Oxr1, Plxna2, and Tbc1d31) independently tied to various tumour characteristics, designated as a mTSGS. hTSGS scores (hTSGSS) based on their transcriptional level showed prognostic values, superseding clinical factors and PAM50 subtype across multiple human BC cohorts, and predicted pathological complete response independent of and superior to MammaPrint score in I-SPY2 study. The power of mTSGS score for predicting chemotherapy response was further validated in an in vivo mouse MMTV-Erbb2 model, showing that, like findings in human patients, mouse tumours with low mTSGS scores were most likely to respond to treatment. INTERPRETATION: Our investigation has unveiled many new genes predisposing individuals to ERBB2-driven cancer. Translational findings indicate that hTSGS holds promise as a biomarker for refining treatment strategies for patients with BC. FUNDING: The U.S. Department of Defense (DoD) Breast Cancer Research Program (BCRP) (BC190820), United States; MCIN/AEI/10.13039/501100011039 (PID2020-118527RB-I00, PDC2021-121735-I00), the European Union Next Generation EU/PRTR, the Regional Government of Castile and León (CSI144P20), European Union.

BACKGROUND: Luminal A tumours generally have a favourable prognosis but possess the highest 10-year recurrence risk among breast cancers. Additionally, a quarter of the recurrence cases occur within 5 years post-diagnosis. Identifying such patients is crucial as long-term relapsers could benefit from extended hormone therapy, while early relapsers might require more aggressive treatment. METHODS: We conducted a study to explore non-structural chromosome maintenance condensin I complex subunit Hs (NCAPH) role in luminal A breast cancer pathogenesis, both in vitro and in vivo, aiming to identify an intratumoural gene expression signature, with a focus on elevated NCAPH levels, as a potential marker for unfavourable progression. Our analysis included transgenic mouse models overexpressing NCAPH and a genetically diverse mouse cohort generated by backcrossing. A least absolute shrinkage and selection operator (LASSO) multivariate regression analysis was performed on transcripts associated with elevated intratumoural NCAPH levels. RESULTS: We found that NCAPH contributes to adverse luminal A breast cancer progression. The intratumoural gene expression signature associated with elevated NCAPH levels emerged as a potential risk identifier. Transgenic mice overexpressing NCAPH developed breast tumours with extended latency, and in Mouse Mammary Tumor Virus (MMTV)-NCAPHErbB2 double-transgenic mice, luminal tumours showed increased aggressiveness. High intratumoural Ncaph levels correlated with worse breast cancer outcome and subpar chemotherapy response. A 10-gene risk score, termed Gene Signature for Luminal A 10 (GSLA10), was derived from the LASSO analysis, correlating with adverse luminal A breast cancer progression. CONCLUSIONS: The GSLA10 signature outperformed the Oncotype DX signature in discerning tumours with unfavourable outcomes, previously categorised as luminal A by Prediction Analysis of Microarray 50 (PAM50) across three independent human cohorts. This new signature holds promise for identifying luminal A tumour patients with adverse prognosis, aiding in the development of personalised treatment strategies to significantly improve patient outcomes.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.

Soil permeability tests require a time series of water level measurements to determine system losses, including both infiltration and evaporation. Laboratory measurements of flow are standardised by international regulations such as ASTM International, ISO or UNE, but field measurements are not as well described and in some cases may require definition and specification of test conditions. This is the case for geosynthetic clay liner (GCL) products, where permeability is assessed by a laboratory measurement using a flexible wall permeameter as defined in standard test method D 5887-04. This method is not able to evaluate the performance of such products in the field and therefore cannot guarantee their ability to be used for the repair of landfill liner overlays. For this reason, we have defined a field test in a confined steel ring and developed a real-time ultrasonic IoT device to evaluate water losses over a period of time. The test method was applied in Mallorca (Spain) and as a result the quality of a landfill cover repair solution was evaluated, the corresponding civil works were carried out and the basis for future field measurements of soil permeability tests on different materials and conditions was established.

Summary: Background: Deeper insights into ERBB2-driven cancers are essential to develop new treatment approaches for ERBB2+ breast cancers (BCs). We employed the Collaborative Cross (CC) mouse model to unearth genetic factors underpinning Erbb2-driven mammary tumour development and metastasis. Methods: 732 F1 hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains were monitored for mammary tumour phenotypes. GWAS pinpointed SNPs that influence various tumour phenotypes. Multivariate analyses and models were used to construct the polygenic score and to develop a mouse tumour susceptibility gene signature (mTSGS), where the corresponding human ortholog was identified and designated as hTSGS. The importance and clinical value of hTSGS in human BC was evaluated using public datasets, encompassing TCGA, METABRIC, GSE96058, and I-SPY2 cohorts. The predictive power of mTSGS for response to chemotherapy was validated in vivo using genetically diverse MMTV-Erbb2 mice. Findings: Distinct variances in tumour onset, multiplicity, and metastatic patterns were observed in F1-hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains. Besides lung metastasis, liver and kidney metastases emerged in specific CC strains. GWAS identified specific SNPs significantly associated with tumour onset, multiplicity, lung metastasis, and liver metastasis. Multivariate analyses flagged SNPs in 20 genes (Stx6, Ramp1, Traf3ip1, Nckap5, Pfkfb2, Trmt1l, Rprd1b, Rer1, Sepsecs, Rhobtb1, Tsen15, Abcc3, Arid5b, Tnr, Dock2, Tti1, Fam81a, Oxr1, Plxna2, and Tbc1d31) independently tied to various tumour characteristics, designated as a mTSGS. hTSGS scores (hTSGSS) based on their transcriptional level showed prognostic values, superseding clinical factors and PAM50 subtype across multiple human BC cohorts, and predicted pathological complete response independent of and superior to MammaPrint score in I-SPY2 study. The power of mTSGS score for predicting chemotherapy response was further validated in an in vivo mouse MMTV-Erbb2 model, showing that, like findings in human patients, mouse tumours with low mTSGS scores were most likely to respond to treatment. Interpretation: Our investigation has unveiled many new genes predisposing individuals to ERBB2-driven cancer. Translational findings indicate that hTSGS holds promise as a biomarker for refining treatment strategies for patients with BC. Funding: The U.S. Department of Defense (DoD) Breast Cancer Research Program (BCRP) (BC190820), United States; MCIN/AEI/10.13039/501100011039 (PID2020-118527RB-I00, PDC2021-121735-I00), the “European Union Next Generation EU/PRTR,” the Regional Government of Castile and León (CSI144P20), European Union.

Climate change is a major issue in wastewater management at local and regional levels, as it affects the frequency of flooding and therefore the need to update infrastructure and design regulations. To this end, rainfall data are the main input to hydraulic models used for the design of drainage systems and, in advanced contexts, for their real-time monitoring. Field observations are of great interest and water authorities are increasing the number of existing rain gauges, but at present they are scarce and require maintenance, so their number needs to be considered with their O&M costs. Remote sensors, including both the existing satellite rain products (SRPs) and radar imagery (RI), can complete the spatial distribution of rainfall and optimise the cost of observations. While most SRPs are based on re-analysis and have a lag in availability, RI can be obtained in near real time and is becoming increasingly popular in weather forecasting applications. Unfortunately, actual rainfall forecasts from RI observations are not accurate enough for real-time monitoring of drainage systems. In this paper, the Colour Pattern Regression (CPR) algorithm is used to recalibrate the 6 h rainfall values from RI provided by the Agencia Estatal de Meteorología (AEMET) with the observed rain gauge data, using as a case study the metropolitan area of Palma (Spain).

Metabolic changes that facilitate tumor growth are one of the hallmarks of cancer. These changes are not specific to tumors but also take place during the physiological growth of tissues. Indeed, the cellular and tissue mechanisms present in the tumor have their physiological counterpart in the repair of tissue lesions and wound healing. These molecular mechanisms have been acquired during metazoan evolution, first to eliminate the infection of the tissue injury, then to enter an effective regenerative phase. Cancer itself could be considered a phenomenon of antagonistic pleiotropy of the genes involved in effective tissue repair. Cancer and tissue repair are complex traits that share many intermediate phenotypes at the molecular, cellular, and tissue levels, and all of these are integrated within a Systems Biology structure. Complex traits are influenced by a multitude of common genes, each with a weak effect. This polygenic component of complex traits is mainly unknown and so makes up part of the missing heritability. Here, we try to integrate these different perspectives from the point of view of the metabolic changes observed in cancer.

Abstract Background Luminal A tumours generally have a favourable prognosis but possess the highest 10‐year recurrence risk among breast cancers. Additionally, a quarter of the recurrence cases occur within 5 years post‐diagnosis. Identifying such patients is crucial as long‐term relapsers could benefit from extended hormone therapy, while early relapsers might require more aggressive treatment. Methods We conducted a study to explore non‐structural chromosome maintenance condensin I complex subunit H’s (NCAPH) role in luminal A breast cancer pathogenesis, both in vitro and in vivo, aiming to identify an intratumoural gene expression signature, with a focus on elevated NCAPH levels, as a potential marker for unfavourable progression. Our analysis included transgenic mouse models overexpressing NCAPH and a genetically diverse mouse cohort generated by backcrossing. A least absolute shrinkage and selection operator (LASSO) multivariate regression analysis was performed on transcripts associated with elevated intratumoural NCAPH levels. Results We found that NCAPH contributes to adverse luminal A breast cancer progression. The intratumoural gene expression signature associated with elevated NCAPH levels emerged as a potential risk identifier. Transgenic mice overexpressing NCAPH developed breast tumours with extended latency, and in Mouse Mammary Tumor Virus (MMTV)‐NCAPHErbB2 double‐transgenic mice, luminal tumours showed increased aggressiveness. High intratumoural Ncaph levels correlated with worse breast cancer outcome and subpar chemotherapy response. A 10‐gene risk score, termed Gene Signature for Luminal A 10 (GSLA10), was derived from the LASSO analysis, correlating with adverse luminal A breast cancer progression. Conclusions The GSLA10 signature outperformed the Oncotype DX signature in discerning tumours with unfavourable outcomes, previously categorised as luminal A by Prediction Analysis of Microarray 50 (PAM50) across three independent human cohorts. This new signature holds promise for identifying luminal A tumour patients with adverse prognosis, aiding in the development of personalised treatment strategies to significantly improve patient outcomes.

Ice cream is a solidified dairy product produced by freezing a pasteurized mixture by stirring to incorporate air and guarantee a uniform consistency. This product is in high demand among people of all ages. In the present work, we used the SuperPro Designer® tool to simulate an industrial-scale strawberry ice-cream production plant located in Cuba with an annual production capacity of approximately 830 ice-cream 10 L containers per batch (1 201 770 L per year). Through simulation, the mass and energy balances were determined, as well as the main economic and profitability indicators of the proposed production process. The unit production cost was USD $ 7.04/container, while the annual net profit was USD $ 980 000. The Net Present Value, Internal Rate of Return, and Payback period were USD $ 2 860 000, 24.29 %, and 3.94 years, respectively, which indicate that the proposed strawberry ice-cream production plant is feasible from the technical-economic point of view under the current economic conditions in Cuba.

The Colour Pattern Regression (CPR) algorithm complement for QGIS is presented for determining and quantifying the relationship between aerial images and raster maps. Aerial images can be readily decomposed into their standard RGB spaces that assign numerical values to their colours. According to them, a linear regression can be established to correlate raster values with the colour patterns, and if the model performance is considered satisfactory, the result will provide a raster interpolation with finest resolution according to colour nuances within the aerial image. The CPR Algorithm allow both, the calculation of the regression coefficient and the evaluation of the goodness of fit of the model. The use of the present QGIS complement could enable the study of the relationships of aerial images and earth surface products – e.g. soil moisture content, landcover, vegetation and forests, soils, urban heat islands – or marine products – e.g. chlorophyll, total suspended solids. The tool is open source and will be readily adapted with additional features and improved general performance ratings thresholds for the physical problems to be solved.

Environmental and water quality monitoring are of utmost interest in a context where land use changes, uncontrolled agricultural practices, human settlements, tourism and other activities affect a watershed and condition the usage of their surface waters. Such is the case of Mar Menor lagoon in Southeast of Spain, where the EU H2020 SMARTLAGOON project stands and is implementing an intelligent environmental infrastructure and modelling that will let the construction of a digital twin of the lagoon. Performing environmental monitoring is expensive and the number of sampling locations is typically limited by the budget. For this reason, we have developed a low-cost monitoring system that can be integrated in a small-sized buoy and attached to fishing and recreational boats allowing citizens to gather water quality information – i.e. electrical conductivity and temperature – with the use of their smartphones. The usage of such devices leads to key stakeholder engagement and citizen science activities that could enrich and ease the data gathering process.

In the emotional narrative of sports event tourism, visual communication is key to persuading media consumers. Our aim is to examine the interplay between context (sports tourism) and text (visual and written) to shed light on the storytelling of blogs and online articles regarding sports tourism. Results show that the narrative sequence of the images, supported by text, highlights central values of sports, such as leadership, teamwork, and respect, in which the host city integrates. The emotions reflected in the corpus images point to the construction of a well-defined national identity in tourism social media when applied to sports events. [ABSTRACT FROM AUTHOR]

Climate change is a major issue in wastewater management at local and regional levels, as it affects the frequency of flooding and therefore the need to update infrastructure and design regulations. To this end, rainfall data are the main input to hydraulic models used for the design of drainage systems and, in advanced contexts, for their real-time monitoring. Field observations are of great interest and water authorities are increasing the number of existing rain gauges, but at present they are scarce and require maintenance, so their number needs to be considered with their O&M costs. Remote sensors, including both the existing satellite rain products (SRPs) and radar imagery (RI), can complete the spatial distribution of rainfall and optimise the cost of observations. While most SRPs are based on re-analysis and have a lag in availability, RI can be obtained in near real time and is becoming increasingly popular in weather forecasting applications. Unfortunately, actual rainfall forecasts from RI observations are not accurate enough for real-time monitoring of drainage systems. In this paper, the Colour Pattern Regression (CPR) algorithm is used to recalibrate the 6 h rainfall values from RI provided by the Agencia Estatal de Meteorología (AEMET) with the observed rain gauge data, using as a case study the metropolitan area of Palma (Spain). [ABSTRACT FROM AUTHOR]

Only a small number of infected people are highly susceptible to schistosomiasis, showing high levels of infection or severe liver fibrosis. The susceptibility to schistosome infection is influenced by genetic background. To assess the genetic basis of susceptibility and identify the chromosomal regions involved, a backcross strategy was employed to generate high variation in schistosomiasis susceptibility. This strategy involved crossing the resistant C57BL/6J mouse strain with the susceptible CBA/2J strain. The resulting F1 females (C57BL/6J × CBA/2J) were then backcrossed with CBA/2J males to generate the backcross (BX) cohort. The BX mice exhibited a range of phenotypes, with disease severity varying from mild to severe disease, lacking a fully resistant group. We observed four levels of infection intensity using cluster and principal component analyses and K-means based on parasitological, pathological, and immunological trait measurements. The mice were genotyped with 961 informative SNPs, leading to the identification of 19 new quantitative trait loci (QTL) associated with parasite burden, liver lesions, white blood cell populations, and antibody responses. Two QTLs located on chromosomes 15 and 18 were linked to the number of granulomas, liver lesions, and IgM levels. The corresponding syntenic human regions are located in chromosomes 8 and 18. None of the significant QTLs had been reported previously.

The data presented in this article are related to the research paper entitled "The biological age linked to oxidative stress modifies breast cancer aggressiveness" (M.M. Sáez-Freire, A. Blanco-Gómez, S. Castillo-Lluva, A. Gómez-Vecino, J.M. Galvis-Jiménez, C. Martín-Seisdedos, M. Isidoro-García, L. Hontecillas-Prieto, M.B. García-Cenador, F.J. García-Criado, M.C. Patino-Alonso, P. Galindo-Villardón, J.H. Mao, C. Prieto, A. Castellanos-Martín, L. Kaderali, J. Pérez-Losada). The data shown were obtained from a population of transgenic mice, MMTV-Erbb2/Neu, with different susceptibility to breast cancer and a mixed genetic background generated by backcrossing. It was observed that the aggressiveness of breast cancer negatively correlates with age, being lower in chronologically old mice, similar to what occurs in humans. Given that oxidative stress is associated with tumour susceptibility and the degree of aging, the association between the aggressiveness of breast cancer and multiple intermediate phenotypes directly or indirectly related to oxidative stress was studied. Using a mathematical model, we defined biological age and the degree of aging as the difference between biological and chronological ages. As a result, we observed that biologically old mice predominated among those that developed the disease early on, that is, those that were chronologically young. We then identified the specific and common genetic components of Quantitative Trait loci or QTL associated with different evolution of breast cancer, the intermediate phenotypes related to oxidative stress studied, the biological age and the degree of aging. Lastly, we showed that the expression pattern in the livers of biologically old mice were enriched in signalling pathways related to inflammation and response to infections; whereas the biologically young mice exhibited enriched pathways related to mitochondrial activity. For the explanation and discussion of these data refer to the research article cited above.

The data presented in this article are related to the research paper entitled "The biological age linked to oxidative stress modifies breast cancer aggressiveness" (M.M. Sáez-Freire, A. Blanco-Gómez, S. Castillo-Lluva, A. Gómez-Vecino, J.M. Galvis-Jiménez, C. Martín-Seisdedos, M. Isidoro-García, L. Hontecillas-Prieto, M.B. García-Cenador, F.J. García-Criado, M.C. Patino-Alonso, P. Galindo-Villardón, J.H. Mao, C. Prieto, A. Castellanos-Martín, L. Kaderali, J. Pérez-Losada). The data shown were obtained from a population of transgenic mice, MMTV-Erbb2/Neu, with different susceptibility to breast cancer and a mixed genetic background generated by backcrossing. It was observed that the aggressiveness of breast cancer negatively correlates with age, being lower in chronologically old mice, similar to what occurs in humans. Given that oxidative stress is associated with tumour susceptibility and the degree of aging, the association between the aggressiveness of breast cancer and multiple intermediate phenotypes directly or indirectly related to oxidative stress was studied. Using a mathematical model, we defined biological age and the degree of aging as the difference between biological and chronological ages. As a result, we observed that biologically old mice predominated among those that developed the disease early on, that is, those that were chronologically young. We then identified the specific and common genetic components of Quantitative Trait loci or QTL associated with different evolution of breast cancer, the intermediate phenotypes related to oxidative stress studied, the biological age and the degree of aging. Lastly, we showed that the expression pattern in the livers of biologically old mice were enriched in signalling pathways related to inflammation and response to infections; whereas the biologically young mice exhibited enriched pathways related to mitochondrial activity. For the explanation and discussion of these data refer to the research article cited above.

The incidence of breast cancer increases with age until menopause, and breast cancer is more aggressive in younger women. The existence of epidemiological links between breast cancer and aging indicates that both processes share some common mechanisms of development. Oxidative stress is associated with both cancer susceptibility and aging. Here we observed that ERBB2-positive breast cancer, which developed in genetically heterogeneous ERBB2-positive transgenic mice generated by a backcross, is more aggressive in chronologically younger than in older mice (differentiated by the median survival of the cohort that was 79 weeks), similar to what occurs in humans. In this cohort, we estimated the oxidative biological age using a mathematical model that integrated several subphenotypes directly or indirectly related to oxidative stress. The model selected the serum levels of HDL-cholesterol and magnesium and total AKT1 and glutathione concentrations in the liver. The grade of aging was calculated as the difference between the predicted biological age and the chronological age. This comparison permitted the identification of biologically younger and older mice compared with their chronological age. Interestingly, biologically older mice developed more aggressive breast cancer than the biologically younger mice. Genomic regions on chromosomes 2 and 15 linked to the grade of oxidative aging were identified. The levels of expression of Zbp1 located on chromosome 2, a gene related to necroptosis and inflammation, positively correlated with the grade of aging and tumour aggressiveness. Moreover, the pattern of gene expression of genes linked to the inflammation and the response to infection pathways was enriched in the livers of biologically old mice. This study shows part of the complex interactions between breast cancer and aging.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.

The methyl-CpG binding protein 2 gene (MECP2) encodes an epigenetic transcriptional regulator implicated in neuronal plasticity. Loss-of-function mutations in this gene are the primary cause of Rett syndrome and, to a lesser degree, of other neurodevelopmental disorders. Recently, we demonstrated that both Mecp2 haploinsuficiency and mild early life stress decrease anxiety-like behaviours and neuronal activation in brain areas controlling these responses in adolescent female mice. Here, we extend this work to males by using Mecp2-null and wild type adolescent mice subjected to maternal separation and their non-stressed controls. We assessed their behavioural responses in a battery of anxiety-provoking tests. Upon exposure to an elevated plus maze in aversive conditions, we evaluated changes in c-FOS expression in stress- and anxiety-related brain regions. In addition, we assessed the impact of maternal separation in neuronal maturation using doublecortin and reelin as surrogate markers. Mutant males showed reduced motor abilities, increased activation of the olfactory bulbs, probably due to breathing abnormalities, and decreased activation of the paraventricular thalamic nucleus, when compared to wild type mice. In addition, maternal separation increased the number of immature doublecortin-like neurons found in Mecp2-null animals. Moreover, this work shows for the first time that reelin is decreased in the mutant animals at the olfactory tubercle, piriform cortex and hippocampal dentate gyrus, an effect also associated to maternal separation. Taken together, our results suggest that maternal separation exacerbates some phenotypical alterations associated with lack of MeCP2 in adolescent males.

Diseases of complex origin have a component of quantitative genetics that contributes to their susceptibility and phenotypic variability. However, after several studies, a major part of the genetic component of complex phenotypes has still not been found, a situation known as "missing heritability." Although there have been many hypotheses put forward to explain the reasons for the missing heritability, its definitive causes remain unknown. Complex diseases are caused by multiple intermediate phenotypes involved in their pathogenesis and, very often, each one of these intermediate phenotypes also has a component of quantitative inheritance. Here we propose that at least part of the missing heritability can be explained by the genetic component of intermediate phenotypes that is not detectable at the level of the main complex trait. At the same time, the identification of the genetic component of intermediate phenotypes provides an opportunity to identify part of the missing heritability of complex diseases.

Introduction: pemphigoid vulgaris is a rare, severe, autoimmune disease with mucocutaneous involvement that has an aggressive course and chronic evolution. The origin depends on the interaction between predisposing genetic and environmental factors, which induce an immune response of the host against epidermal desmosomes. Case report: 31-year-old pregnant woman at 31,2 weeks, who presented vesiculo-ampullary lesions at the periumbilical level at the beginning, and later extending all over the thorax, face along with upper and lower limbs, without mucosal involvement. A range of complementary tests were performed and a diagnosis of pemphigoid gestationalis vulgaris was made; treatment was started with prednisone, diphenhydramine, ciprofloxacin and clobetasol cream on the lesions, treatment was maintained until delivery, however, a new outbreak appeared, so azathioprine was added for 45 days with progressive decrease of prednisone, showing clinical improvement. Conclusions: the diagnosis of pemphigus vulgaris requires a high index of suspicion to avoid delay in treatment and improve prognosis. Given the similarity with other more prevalent exanthematous diseases, it is necessary when there are diagnostic doubts in cases of unexpected evolution, to reevaluate the clinical manifestations together with the specialist and perform skin biopsy in the lesions and peri-lesions with histological study and direct immunofluorescence to confirm diagnosis.

Fundamento: una maternidad segura, libre de riesgos para la madre e hijo, en fase epidémica por COVID-19, requiere de cuidados y competencias específicas por el personal de enfermería. Objetivo: diseñar una guía para el desarrollo de competencias obstétricas en estudiantes de tercer año de Licenciatura en Enfermería, para el cuidado prenatal en la comunidad, con enfoque preventivo de la COVID-19. Métodos: se realizó una investigación de desarrollo durante las actividades de pesquisa activa de síntomas respiratorios por COVID-19, en el Policlínico Universitario “Dr. Gustavo Aldereguía Lima”, de Las Tunas, entre marzo y junio de 2020. A una muestra intencionada de diez estudiantes de tercer año de Licenciatura en Enfermería, que controlaban mujeres embarazadas, se les realizó una entrevista a profundidad para identificar las necesidades de aprendizaje. Se revisaron los protocolos de actuación ante la COVID-19 y el manejo de la embarazada en la comunidad. Se seleccionó un comité de 13 expertos que, en talleres de opinión crítica, delimitaron los saberes a incorporar en los estudiantes. Resultados: en la guía se definieron 27 tareas y 15 competencias específicas, que responden a la atención prenatal con enfoque preventivo de la COVID-19. Abarca tres dimensiones: reconocimiento de las modificaciones y complicaciones del organismo materno y las manifestaciones clínicas de la enfermedad; los cambios conductuales a promover en la embarazada y familia para generar un autocuidado seguro y libre de riesgo; y la inclusión de actividades de prevención para vivir en una comunidad consciente, con prácticas sanitarias adecuadas. Conclusiones: se elaboró la guía para competencias obstétricas en estudiantes de enfermería.

Breast cancer is a major cause of mortality in women. The transcription factor SNAI2 has been implicated in the pathogenesis of several types of cancer, including breast cancer of basal origin. Here we show that SNAI2 is also important in the development of breast cancer of luminal origin in MMTV-ErbB2 mice. SNAI2 deficiency leads to longer latency and fewer luminal tumors, both of these being characteristics of pretumoral origin. These effects were associated with reduced proliferation and a decreased ability to generate mammospheres in normal mammary glands. However, the capacity to metastasize was not modified. Under conditions of increased ERBB2 oncogenic activity after pregnancy plus SNAI2 deficiency, both pretumoral defects-latency and tumor load-were compensated. However, the incidence of lung metastases was dramatically reduced. Furthermore, SNAI2 was required for proper postlactational involution of the breast. At 3 days post lactational involution, the mammary glands of Snai2-deficient mice exhibited lower levels of pSTAT3 and higher levels of pAKT1, resulting in decreased apoptosis. Abundant noninvoluted ducts were still present at 30 days post lactation, with a greater number of residual ERBB2+ cells. These results suggest that this defect in involution leads to an increase in the number of susceptible target cells for transformation, to the recovery of the capacity to generate mammospheres and to an increase in the number of tumors. Our work demonstrates the participation of SNAI2 in the pathogenesis of luminal breast cancer, and reveals an unexpected connection between the processes of postlactational involution and breast tumorigenesis in Snai2-null mutant mice.

BackgroundAn essential question in cancer is why individuals with the same disease have different clinical outcomes. Progress toward a more personalized medicine in cancer patients requires taking into account the underlying heterogeneity at different molecular levels.ResultsHere, we present a model in which there are complex interactions at different cellular and systemic levels that account for the heterogeneity of susceptibility to and evolution of ERBB2-positive breast cancers. Our model is based on our analyses of a cohort of mice that are characterized by heterogeneous susceptibility to ERBB2-positive breast cancers. Our analysis reveals that there are similarities between ERBB2 tumors in humans and those of backcross mice at clinical, genomic, expression, and signaling levels. We also show that mice that have tumors with intrinsically high levels of active AKT and ERK are more resistant to tumor metastasis. Our findings suggest for the first time that a site-specific phosphorylation at the serine 473 residue of AKT1 modifies the capacity for tumors to disseminate. Finally, we present two predictive models that can explain the heterogeneous behavior of the disease in the mouse population when we consider simultaneously certain genetic markers, liver cell signaling and serum biomarkers that are identified before the onset of the disease.ConclusionsConsidering simultaneously tumor pathophenotypes and several molecular levels, we show the heterogeneous behavior of ERBB2-positive breast cancer in terms of disease progression. This and similar studies should help to better understand disease variability in patient populations.

Presentamos la experiencia inicial con la realización de 14 gastrostomías percutáneas con control fluoroscópico en el Servicio de Radiología del Hospital Universitario San Vicente de Paúl de Medellín, con elementos fácilmente disponibles y económicos. Se transcribe el procedimiento y se analizan indicaciones y morbimortalidad comparadas con un grupo de gastrostomías quirúrgicas realizadas en la misma institución. Concluimos que por su bajo costo, fácil aprendizaje y realización y baja morbilidad, la gastrostomía percutánea radiológica es una excelente alternativa para los pacientes que la requieran.

Metabolic changes that facilitate tumor growth are one of the hallmarks of cancer. These changes are not specific to tumors but also take place during the physiological growth of tissues. Indeed, the cellular and tissue mechanisms present in the tumor have their physiological counterpart in the repair of tissue lesions and wound healing. These molecular mechanisms have been acquired during metazoan evolution, first to eliminate the infection of the tissue injury, then to enter an effective regenerative phase. Cancer itself could be considered a phenomenon of antagonistic pleiotropy of the genes involved in effective tissue repair. Cancer and tissue repair are complex traits that share many intermediate phenotypes at the molecular, cellular, and tissue levels, and all of these are integrated within a Systems Biology structure. Complex traits are influenced by a multitude of common genes, each with a weak effect. This polygenic component of complex traits is mainly unknown and so makes up part of the missing heritability. Here, we try to integrate these different perspectives from the point of view of the metabolic changes observed in cancer.

Introduction: Langerhans cell histiocytosis (LCH) or Histiocytosis X is a benign proliferative disease affecting dendritic cells. It presents a wide clinical spectrum, from isolated eosinophilic bone granuloma to multisystem involvement with multiple organ failure with or without resistance to chemotherapy. Case report: a 4-month-old male infant, with no family history of hematooncologic disease; his condition began two months earlier with lesions on the scalp, trunk, axillae and inguinal folds, and irritability. The family physician prescribed non-steroidal anti-inflammatory drugs with no improvement and the patient was referred to the dermatology department. Clinical examination revealed adynamia, hyporexia and weight loss, increased irritability on palpation of the hips, increased volume of the left leg and cervical lymphadenopathy. Additional tests were performed and a diagnosis of Langerhans cell histiocytosis was made. Treatment was started with six mercaptopurine and vinblastine, blood product transfusions and treatment with Filgastrim, the patient showed clinical improvement. Conclusions: Langerhans cell histiocytosis is a complex and rare disease which pathophysiology and prognosis have not yet been widely described. It is difficult to diagnose due to its heterogeneous presentation and its treatment must be individualized. This disease represents a challenge, and it is important to raise awareness among medical personnel of the need to deepen their knowledge with reference to the disease in order to establish a timely diagnosis and management.

Introduccion La histiocitosis de Células de Langerhans es una enfermedad proliferativa benigna que afecta a las células dendríticas. La etiología de la enfermedad continúa siendo controversial. Presenta un amplio espectro clínico, desde el granuloma eosinófilo óseo aislado, hasta la afectación multisistémica con fallo orgánico que puede ser resistente a la quimioterapia. Presentación del caso Lactante de sexo masculino de 4 meses, sin antecedentes familiares de enfermedades hematooncológicas; inició su padecimiento dos meses antes con lesiones en el cuero cabelludo , en el tronco , los pliegues axilares e inguinales e irritabilidad; el médico de la familia prescribió AINES sin mejoría y remitió al paciente al servicio de Dermatología; a la exploración clínica se encontró con adinamia e hiporexia y pérdida de peso; incremento de la irritabilidad a la palpación de las caderas, aumento de volumen de la pierna izquierda y adenopatías cervicales. Se le realizaron deferentes complementarios y se llegó al diagnóstico de histiocitosis de células de Langerhans; se inició tratamiento con seis mercaptopurina y vinblastina, transfusiones de hemoderivados, tratamiento con Filgastrim, mostrando mejoría clínica. Conclusiones La histiocitosis de células de Langerhans es una enfermedad compleja y poco frecuente cuya fisiopatología y pronóstico aún no se han descrito ampliamente. Es de difícil diagnostico por su presentación heterogénea. El tratamiento debe ser individualizado. Por ello, la enfermedad representa un desafío y es importante sensibilizar al personal médico sobre la necesidad de profundizar en su conocimiento para un diagnóstico y manejo oportunos.