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Background Associations between anthropometric measures and patient outcomes in children are inconsistent and mainly based on data at kidney replacement therapy (KRT) initiation. We studied associations of height and body mass index (BMI) with access to kidney transplantation, graft failure, and death during childhood KRT. Methods We included patients 1.88. Underweight, overweight and obesity were calculated using age and sex-specific BMI for height-age criteria. Associations with outcomes were assessed using multivariable Cox models with time-dependent covariates. Results We included 11,873 patients. Likelihood of transplantation was lower for short (aHR: 0.82, 95% CI: 0.78–0.86), tall (aHR: 0.65, 95% CI: 0.56–0.75), and underweight patients (aHR: 0.79, 95%CI: 0.71–0.87). Compared with normal height, patients with short and tall statures showed higher graft failure risk. All-cause mortality risk was higher in short (aHR: 2.30, 95% CI: 1.92–2.74), but not in tall stature. Underweight (aHR: 1.76, 95% CI: 1.38–2.23) and obese (aHR: 1.49, 95% CI: 1.11–1.99) patients showed higher all-cause mortality risk than normal weight subjects. Conclusions Short and tall stature and being underweight were associated with a lower likelihood of receiving a kidney allograft. Mortality risk was higher among pediatric KRT patients with a short stature or those being underweight or obese. Our results highlight the need for careful nutritional management and multidisciplinary approach for these patients. Graphical abstract

Introducción: La concentración e integridad del ADN libre circulante (ADN-lc) son biomarcadores de diagnóstico y pronóstico en múltiples padecimientos. Objetivo. Determinar la concentración e índice de integridad del ADN-lc en una muestra de población general de Jalisco, México. Método. Se analizaron muestras de sangre periférica de 117 personas procedentes de Jalisco. El ADN-lc se cuantificó mediante fluorometría Qubit 2.0 y amplificación por q-PCR de ALU115. El índice de integridad se determinó por la relación de los amplificados ALU247/ALU115. Resultados. La concentración media de ADN-lc mostró 294 ng/ml por fluorometría Qubit 2.0 y 108.08 ng/ml por q-PCR. El índice de integridad calculado por la relación ALU247/ALU115 fue 0.45. La concentración mostró diferencia significativa por edad, pero no por sexo. El índice de integridad no mostró diferencias significativas por edad ni sexo. Conclusiones. Existen amplias diferencias en ADN-lc entre los dos procedimientos aquí utilizados, así como comparado con otras poblaciones. Palabras claves: ADN libre circulante; Cell-Free DNA; ADN-lc; índice de integridad; población general.

Objective(s): The mitogen-activated protein kinase kinase 4 (MKK4) plays a key role in several processes like inflammation, apoptosis, and tumorigenesis. Several authors have proposed that genetic variations in these genes may alter their expression with subsequent cancer risk. This study aimed to examine the possible association of MKK4 rs3826392 and rs3809728 variants in Mexican patients with colorectal cancer (CRC). These variants were also compared with clinical features as sex, age, TNM stage, and tumor location. Materials and Methods: The study included genomic DNA from 218 control subjects and 250 patients. Genotyping of the MKK4 variants was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) procedure. Results: Individuals with A/T and T/T genotypes for the rs3809728 (-1044 A>T) variant showed a significantly increased risk for CRC (P=0.012 and 0.007, respectively); while individuals with the G/G genotype for the rs3826392 (-1304 T>G) variant showed a decreased risk for CRC (P=0.012). Genotypes of the MKK4 rs3809728 variant were also significantly related to colon localization and advanced TNM stage in CRC patients. T-T haplotype (rs3826392 and rs3809728) of the MKK4 gene was associated with risk in patients with CRC. Conclusion: The rs3826392 variant in the MKK4 gene could be a cancer protective factor, while the rs3809728 variant could be a risk factor. These variants play a significant role in CRC risk.

Background The complement factor H antibody (CFH-Ab)–associated hemolytic uremic syndrome (HUS) forms a distinct subgroup within the complement-mediated HUS disease spectrum. The autoimmune nature of this HUS subgroup implies the potential benefit of a targeted immunosuppressive therapy. Data on long-term outcome are scarce. Methods This observational study evaluates the clinical outcome of 19 pediatric CFH-Ab HUS patients from disease onset until their 5-year follow-up. Results All but one relapse occurred during the first 2 years, and patients who had no relapse within the first 6 months were relapse-free until the end of the observation period. Kidney function at disease onset determines long-term kidney function: all individuals with normal kidney function at disease onset had normal kidney function after 5 years, and all patients with reduced kidney function at onset had impaired kidney function at the last follow-up. Level of CFH-Ab titer at disease onset was not correlated with a higher risk of recurrences or worse long-term outcome after 5 years. Resolution of CFH-Ab titers after 5 years was common. Conclusions CFH-Ab HUS patients have a varied overall long-term course. Early relapses are common, making close surveillance during the first years essential, regardless of the initial CFH-Ab titer.

Se sabe que el Análisis de Fluctuaciones sin Tendencia o DFA (Detrended Fluctuations Analysis, por sus siglas en inglés) de las series de tiempo biológicas como el Electrocardiograma (ECG), el Electroencefalograma (EEG) y otras resulta ser una herramienta útil para discriminar entre la salud o la enfermedad. Con el fin de corroborar si existen diferencias entre los DFA de Adultos Mayores (AM) con Deterioro Cognitivo (DC) y sin Deterioro Cognitivo (sDC), se realizaron DFA en dos sujetos, cada uno de ellos diagnosticado con DC o sDC. Se obtuvieron los registros de EEG y Electromiografía (EMG) durante la condición de vigilia con ojos cerrados. Se desarrolló una interfaz amigable en Python con la que se selecciona la serie de tiempo para el cálculo de los DFA. Se observó que en reposo con ojos cerrados, el sujeto con DC presenta mayores valores en regiones frontales que aquel sujeto sDC. Se concluye que el DFA aporta información cuantificable sobre la localización y mecanismos subyacentes al DC que pueden servir para ayudar a monitorear el curso del DC del AM.

Colorectal cancer is the third cause of cancer and the second leading cause of death worldwide. The CD44 gene plays a key role in malignant processes, including growth, survival, epithelial to mesenchymal transition and metastasis. It is also known that some variants as rs187116 (c.67+4883G>A) and rs7116432 (c.2024+779A>G) can modulate the function of the CD44 gene and malignant transformation in several neoplasms. This study aims to explore, for the first time, the association of the CD44 rs187116 and rs7116432 variants in patients with colorectal cancer. Genomic DNA from 250 patients and 250 healthy blood donors were analyzed. The identification of variants was made by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test and multivariate analysis. Individuals carrying the G/A and A/A genotypes for the rs187116 polymorphism showed an increased risk for colorectal cancer (OR = 3.11, 95% CI: 1.87-5.16, P = 0.001 and OR = 3.59, 95% CI: 2.06-6.25, P = 0.001, respectively). After adjusting for age and gender, these same genotypes and the G/G genotype of the rs7116432 polymorphism were associated with TNM stage and tumor location in the colon. Moreover, the A-G (rs187116 and rs7116432) haplotype was associated with increased risk; while, the haplotype G-A (rs187116 and rs7116432) was related with decreased risk. In conclusion, our results suggest that the here analyzed CD44 variants are involved with risk, TNM stage and tumor location in colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer in the world. Overall survival is related to clinical stage: more advanced stages show lower survival rates; therefore, they need to be monitored regularly with new, less invasive and more specific biomarkers. The concentration and integrity index of circulating cell-free DNA (ccfDNA) have been proposed as potential diagnostic and prognostic biomarkers for CRC, however, inconsistent results are still observed in different reports. Here we analyze these potential CRC biomarkers in a Mexican population. In this study, 124 patients with sporadic CRC and 37 healthy individuals were examined as a reference group. The ccfDNA was isolated from plasma samples of all included subjects. The ccfDNA concentration was determined by fluorometry and the integrity index (ALU247/ALU115 ratio) by quantitative PCR amplification (qPCR) of ALU sequences. The results show that ccfDNA concentration was higher in CRC patients than in the reference group (P=0.001). The integrity index showed no significant differences between these groups (P=0.258), except for histological type (P=0.012). A higher ccfDNA concentration was also associated with patients younger than 50 years (P=0.030). The ccfDNA concentration showed significant discriminatory power (AUC: 0.854, C.I.: 0.78-0.92, P=0.001) between patients and the reference group and between tumor-node-metastasis (TNM) stages. In conclusion, ccfDNA concentration proves to be a good diagnostic biomarker for CRC patients, whereas the integrity index did not show diagnostic utility.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. The named "destruction complex" has a critical function in the Wnt/β-catenin pathway regulating the level of β-catenin in the cytoplasm and nucleus. Alterations in this complex lead to the cellular accumulation of β-catenin, which participates in the development and progression of CRC. This study aims to determine the contribution of polymorphisms in the genes of the β-catenin destruction complex to develop CRC, specifically adenomatous polyposis coli (APC) (rs11954856 G>T and rs459552 A>T), axis inhibition protein 1 (AXIN1) (rs9921222 C>T and rs1805105 C>T), AXIN2 (rs7224837 A>G), and dishevelled 2 (DVL2) (2074222 G>A and rs222836 C>T). Genomic DNA from 180 sporadic colorectal cancer patients and 150 healthy blood donors were analyzed. The identification of polymorphisms was made by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test. Increased susceptibility to CRC was associated with the polymorphic variants rs11954856 (APC), rs222836 (DVL2), and rs9921222 (AXIN1). Decreased susceptibility was associated with the polymorphisms rs459552 (APC) and 2074222 (DVL2). Association was also observed with advanced Tumor-Node-Metastasis (TNM) stages and tumor location. The haplotypes G-T in APC (rs11954856-rs459552) and A-C in DVL2 (rs2074222-rs222836) were associated with decreased risk of CRC, while the G-T haplotype in the DVL2 gene was associated with increased CRC risk. In conclusion, our results suggest that variants in the destruction complex genes may be involved in the promotion or prevention of colorectal cancer.

During the past years, the VLTI-instrument GRAVITY has made spectacular discoveries with phase-referenced interferometric imaging with milliarcsecond resolution and ten microarcsecond astrometry. Here, we report on the upgrade of the GRAVITY science spectrometer with two new grisms in October 2019, increasing the instrument throughput by a factor > 2. This improvement was made possible by using a high refractive index Germanium substrate, which reduces the grism and groove angles, and by successfully applying an anti-reflection coating to the ruled surface to overcome Fresnel losses. We present the design, manufacturing, and laboratory testing of the new grisms, as well as the results from the re-commissioning on sky.

Background Variants of the estrogen receptor b (ESR2) gene have been associated with different types of cancer. However, these associations have been inconsistent. We genotyped the ESR2 variants (rs1256049, rs4986938, and rs1256030) in breast cancer (BC) patients and in healthy women. Results The variants rs1256049 and rs4986938 in the ESR2 gene were not associated with risk susceptibility in BC patients. However, the rs1256030 variant had an association as a risk factor for BC patients when compared with controls and BC patients for the TT genotype (odds ratio (OR) 1.86, 95% confidence intervals (CI) [1.05–3.28], p = 0.042). In addition, differences were observed in patients and controls carrying the TT genotype under 50 years of age (OR 1.85, 95% CI [1.05–3.27], p = 0.043). Thus, evident differences showed the rs1256030 variant in patients with TT, TC, and TC+TT genotypes with: (1) Stage IV (OR 1.60, 95% CI [1.06–2.54], p = 0.033), and (2) Luminal A (OR 1.60, 95% CI [0.47–0.21], p = 0.041), as well as in BC carriers of the TT genotype with indices of cellular proliferative (Ki-67) elevated (>20%) and overweight (OR 1.67, 95% CI [0.85–3.28], p = 0.041), respectively. In BC HER2 with lymph node metastasis, the TT genotype was a protective factor (OR 0.38, 95% CI [0.18–0.78], p = 0.005). The identification of haplotypes included two common GAT as risk factors (OR 3.1, 95% CI [1.31–7.72], p = 0.011) and GGC as a protective factor (OR 0.7, 95% CI [0.60–0.97], p = 0.034). The haplogenotype GGGATC was a risk factor (OR 2.5, 95% CI [1.28–5.0], p = 0.008). Conclusion The variant rs1256030 (TT) of the ESR2 gene and haplotype GAT were associated with susceptibility to BC as risk factors in this sample from the Mexican population.

Information and Communication Technologies provide great possibilities in the area of health and also represent a motor for change to improve the quality of life of people, particularly the older adult population. The purpose of this article is to present the iBeni web application designed under the Mobile First concept. iBeni web is an application that evaluates and stimulates the cognitive functions of the older adult population and also provides a web and mobile version to the user. To validate the degree of effectiveness of iBeni web, tests were run with 24 users, where 3 rounds were established in the different stages of development of the application. Test analysis indicates that the application and its scaled design mode are rated highly by users. In conclusion, it was possible to demonstrate that cognitive stimulation through a web application with a Mobile First concept is appropriate and enhances the user experience by providing its adaptability in various technological environments.

The rs712 polymorphism in a let-7 microRNA-binding KRAS gene has been associated with different types of cancer, however these associations have been inconsistent. The purpose of this study was to determine the association between rs712 polymorphism in a let-7 microRNA-binding KRAS gene comparing breast cancer (BC) patients with healthy subjects from Mexican population.The genotyping of the rs712 polymorphism was performed by polymerase chain reaction (PCR) in 437 BC patients and 414 healthy women.The observed frequencies of the rs712 polymorphism indicated an associated protective factor for BC in the dominant GT+TT model [odds ratio (OR) 0.70, 95% confidence interval (CI) 0.51-0.97, p=0.040). An association between genotype and BC patients was evident in chemotherapy response (allele GT, OR 0.032, 95% CI 0.002-0.505, p=0.014), partial chemotherapy response (genotype GT, OR 0.023, 95% CI 0.001-0.419, p=0.011), and gastric and hematological toxicity (genotype GT, OR 0.115, 95% CI 0.028-0.473, p=0.003), Luminal A BC patients with gastric and hematological toxicity (genotype TT, OR 0.236, 95% CI 0.069-0.805, p=0.021) and tobacco consumption (genotype TT, OR 0.283, 95% CI 0.001-0.802, p=0.037) and Luminal B with metastatic lymph node (genotype GT, OR 0.241, 95% CI 0.093-0.626, p=0.003).Polymorphism rs712 in KRAS gene was protective factor associated with susceptibility for BC in this sample from Mexican population.

Colorectal cancer is the third cause of cancer and the second leading cause of death worldwide. The CD44 gene plays a key role in malignant processes, including growth, survival, epithelial to mesenchymal transition and metastasis. It is also known that some variants as rs187116 (c.67+4883GA) and rs7116432 (c.2024+779AG) can modulate the function of the CD44 gene and malignant transformation in several neoplasms. This study aims to explore, for the first time, the association of the CD44 rs187116 and rs7116432 variants in patients with colorectal cancer. Genomic DNA from 250 patients and 250 healthy blood donors were analyzed. The identification of variants was made by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test and multivariate analysis. Individuals carrying the G/A and A/A genotypes for the rs187116 polymorphism showed an increased risk for colorectal cancer (OR = 3.11, 95% CI: 1.87-5.16, P = 0.001 and OR = 3.59, 95% CI: 2.06-6.25, P = 0.001, respectively). After adjusting for age and gender, these same genotypes and the G/G genotype of the rs7116432 polymorphism were associated with TNM stage and tumor location in the colon. Moreover, the A-G (rs187116 and rs7116432) haplotype was associated with increased risk; while, the haplotype G-A (rs187116 and rs7116432) was related with decreased risk. In conclusion, our results suggest that the here analyzed CD44 variants are involved with risk, TNM stage and tumor location in colorectal cancer.

Primary focal segmental glomerulosclerosis (FSGS) recurs in up to 55% of patients after kidney transplantation. Herein we report the successful management of recurrent FSGS. A 5‐year‐old boy with primary FSGS received a deceased donor renal transplant. Immediate and fulminant recurrence of FSGS caused anuric graft failure that was resistant to plasmapheresis and rituximab. After exclusion of structural or immunologic damage to the kidney by repeated biopsies, the allograft was retrieved from the first recipient on day 27 and transplanted into a 52‐year‐old second recipient who had vascular nephropathy. Immediately after retransplantation, the allograft regained function with excellent graft function persistent now at 3 years after transplant. After 2 years on hemodialysis, the boy was listed for kidney retransplantation. To prevent FSGS recurrence, pretreatment with ofatumumab was performed. Nephrotic range proteinuria still occurred after the second transplantation, which responded, however, to daily plasma exchange in combination with ofatumumab. At 8 months after kidney retransplantation graft function is good. The clinical course supports the hypothesis of a circulating permeability factor in the pathogenesis of FSGS. Successful ofatumumab pretreatment implicates a key role of B cells. Herein we provide a description of successful management of kidney failure by FSGS, carefully avoiding waste of organs., Successful management of recurrent primary focal segmental glomerulosclerosis after kidney transplantation includes retransplantation of an allograft that failed in the first recipient due to disease recurrence into a second recipient and ofatumumab pretreatment before kidney retransplantation in the patient with fulminant recurrence of focal segmental glomerulosclerosis in the first graft.

Background Arthrogryposis-Renal dysfunction-Cholestasis syndrome (ARC, MIM#208085) is a rare multisystem disease due to mutations in the VPS33B and VIPAR genes, both involved in maintaining apical-basolateral cell polarity. The correlation between mutations and phenotype in the ARC Syndrome is not well described. We report on a 6 year old patient who presented with severe renal Fanconi as first manifestation of ARC related to a combined de novo mutation in the VPS33B gene. Case presentation A 6 year old girl presented during the first year of life with severe renal Fanconi as the first manifestation of ARC-Syndrome. This case presents all defining features of ARC syndrome (including liver, skin and articular manifestations) with predominantly renal impairment at presentation. This novel mutation may be associated with a pronounced renal phenotype in ARC. Furthermore, we report on the successful use of LDL-Apheresis and biliodigestive derivation for treatment of cholestatic pruritus with encouraging results. Conclusion ARC is a heterogeneous disorder with early mortality. This case report contributes to a better understanding of this rare disorder, describes a novel mutation in the VPS33B gene and presents an innovative rescue treatment approach.

Resumen: La mayor parte de los seres vivos son capaces de realizar acciones que pueden ser consideradas inteligentes o al menos el resultado de un proceso de reacción adecuado ante las circunstancias cambiantes de su medio ambiente. Sin embargo, la inteligencia o los procesos intelectuales que desarrollan los seres humanos son enormemente superiores a los que logran los organismos de cualquier otra especie. El cerebro humano adulto es un órgano sumamente complejo: pesa aproximadamente 1.500 g, lo que representa solo el 2% del peso corporal pero consume igual cantidad de energía que todo el músculo esquelético en reposo. Aunque el cerebro humano presenta una estructura típicamente primate, revela algunas características que lo distinguen y lo individualizan plenamente.El proceso de evolución y humanización del cerebro del Homo sapiens (H. sapiens) lo convirtió en un órgano único y diferente, alcanzando el mayor tamaño relativo entre todas las especies, pero además le permitió una reorganización estructural de tejidos y circuitos en segmentos y regiones específicas. Esto explica las notables capacidades cognitivas del hombre moderno, en comparación no solo con otros miembros de su género, sino con otros miembros más antiguos de su propia especie.La evolución del cerebro requirió la coexistencia de 2 mecanismos de adaptación. El primero involucra cambios genéticos que ocurren a nivel de especies y el segundo ocurre a nivel individual e involucra cambios en la organización de la cromatina o cambios epigenéticos. Entre los mecanismos genéticos se encuentran: a) cambios en regiones genéticas codificantes que conducen a cambios en la secuencia y actividad de proteínas existentes; b) los procesos de duplicación y deleción de genes previamente existentes; c) cambios en la expresión génica a través de modificaciones en las secuencias reguladoras de diferentes genes, y d) síntesis de ARNs no codificantes.Finalmente, en esta revisión se describen algunas de las más importantes diferencias cromosómicas reportadas entre humanos y grandes simios, que también han contribuido al proceso de evolución y humanización del cerebro del H. sapiens. Abstract: Most living beings are able to perform actions that can be considered intelligent or, at the very least, the result of an appropriate reaction to changing circumstances in their environment. However, the intelligence or intellectual processes of humans are vastly superior to those achieved by all other species. The adult human brain is a highly complex organ weighing approximately 1500 g, which accounts for only 2% of the total body weight but consumes an amount of energy equal to that required by all skeletal muscle at rest. Although the human brain displays a typical primate structure, it can be identified by its specific distinguishing features.The process of evolution and humanisation of the Homo sapiens brain resulted in a unique and distinct organ with the largest relative volume of any animal species. It also permitted structural reorganization of tissues and circuits in specific segments and regions. These steps explain the remarkable cognitive abilities of modern humans compared not only with other species in our genus, but also with older members of our own species.Brain evolution required the coexistence of two adaptation mechanisms. The first involves genetic changes that occur at the species level, and the second occurs at the individual level and involves changes in chromatin organisation or epigenetic changes. The genetic mechanisms include: a) genetic changes in coding regions that lead to changes in the sequence and activity of existing proteins; b) duplication and deletion of previously existing genes; c) changes in gene expression through changes in the regulatory sequences of different genes; and d) synthesis of non-coding RNAs.Lastly, this review describes some of the main documented chromosomal differences between humans and great apes. These differences have also contributed to the evolution and humanisation process of the H. sapiens brain. Palabras clave: Cerebro humano, Genómica del cerebro, Evolución del cerebro, Keywords: Human brain, Brain genomics, Brain evolution

Most living beings are able to perform actions that can be considered intelligent or, at the very least, the result of an appropriate reaction to changing circumstances in their environment. However, the intelligence or intellectual processes of humans are vastly superior to those achieved by all other species. The adult human brain is a highly complex organ weighing approximately 1500 g, which accounts for only 2% of the total body weight but consumes an amount of energy equal to that required by all skeletal muscle at rest. Although the human brain displays a typical primate structure, it can be identified by its specific distinguishing features.The process of evolution and humanisation of the Homo sapiens brain resulted in a unique and distinct organ with the largest relative volume of any animal species. It also permitted structural reorganisation of tissues and circuits in specific segments and regions. These steps explain the remarkable cognitive abilities of modern humans compared not only with other species in our genus, but also with older members of our own species.Brain evolution required the coexistence of two adaptation mechanisms. The first involves genetic changes that occur at the species level, and the second occurs at the individual level and involves changes in chromatin organisation or epigenetic changes. The genetic mechanisms include: (a) genetic changes in coding regions that lead to changes in the sequence and activity of existing proteins; (b) duplication and deletion of previously existing genes; (c) changes in gene expression through changes in the regulatory sequences of different genes; and (d) synthesis of non-coding RNAs.Lastly, this review describes some of the main documented chromosomal differences between humans and great apes. These differences have also contributed to the evolution and humanisation process of the H. sapiens brain. Resumen: La mayor parte de los seres vivos son capaces de realizar acciones que pueden ser consideradas inteligentes o al menos el resultado de un proceso de reacción adecuado ante las circunstancias cambiantes de su medio ambiente. Sin embargo, la inteligencia o los procesos intelectuales que desarrollan los seres humanos son enormemente superiores a los que logran los organismos de cualquier otra especie. El cerebro humano adulto es un órgano sumamente complejo: pesa aproximadamente 1.500 g, lo que representa solo el 2% del peso corporal pero consume igual cantidad de energía que todo el músculo esquelético en reposo. Aunque el cerebro humano presenta una estructura típicamente primate, revela algunas características que lo distinguen y lo individualizan plenamente.El proceso de evolución y humanización del cerebro del Homo sapiens (H. sapiens) lo convirtió en un órgano único y diferente, alcanzando el mayor tamaño relativo entre todas las especies, pero además le permitió una reorganización estructural de tejidos y circuitos en segmentos y regiones específicas. Esto explica las notables capacidades cognitivas del hombre moderno, en comparación no solo con otros miembros de su género, sino con otros miembros más antiguos de su propia especie.La evolución del cerebro requirió la coexistencia de 2 mecanismos de adaptación. El primero involucra cambios genéticos que ocurren a nivel de especies y el segundo ocurre a nivel individual e involucra cambios en la organización de la cromatina o cambios epigenéticos. Entre los mecanismos genéticos se encuentran: a) cambios en regiones genéticas codificantes que conducen a cambios en la secuencia y actividad de proteínas existentes; b) los procesos de duplicación y deleción de genes previamente existentes; c) cambios en la expresión génica a través de modificaciones en las secuencias reguladoras de diferentes genes, y d) síntesis de ARNs no codificantes.Finalmente, en esta revisión se describen algunas de las más importantes diferencias cromosómicas reportadas entre humanos y grandes simios, que también han contribuido al proceso de evolución y humanización del cerebro del H. sapiens. Keywords: Human brain, Brain genomics, Brain evolution, Palabras clave: Cerebro humano, Genómica del cerebro, Evolución del cerebro

The G2 object has recently passed its pericenter passage in our Galactic Center. While the $Br_\gamma$ emission shows clear signs of tidal interaction, the change in the observed luminosity is only of about a factor of 2, in contention with all previous predictions. We present high resolution simulations performed with the moving mesh code, RICH, together with simple analytical arguments that reproduce the observed $Br_\gamma$ emission. In our model, G2 is a gas cloud that undergoes tidal disruption in a dilute ambient medium. We find that during pericenter passage, the efficient cooling of the cloud results in a vertical collapse, compressing the cloud by a factor of $\sim5000$. By properly taking into account the ionization state of the gas, we find that the cloud is UV starved and are able to reproduce the observed $Br_\gamma$ luminosity. For densities larger than $\approx500\;\mathrm{cm}^{-3}$ at pericenter, the cloud fragments, due to cooling instabilities and the emitted radiation is inconsistent with observations. For lower densities, the cloud survives the pericenter passage intact and its emitted radiation matches the observed lightcurve. From the duration of $Br_\gamma$ emission which contains both redshifted and blueshifted components, we show that the cloud is not spherical but rather elongated with a size ratio of 4 at year 2001. The simulated cloud's elongation grows as it travels towards pericenter and is consistent with observations, due to viewing angles. The simulation is also consistent with having a spherical shape at apocenter.

The start-up of microbial fuel cells (MFCs) requires biofilm development onto electrodes and acclimation of the microbial community to specific substrates. This process is time-consuming and shows low effectivity when complex substrates are utilized. The varying proportions and complex mixtures of volatile fatty acids (VFAs) in bioprocess effluents makes it difficult to predict the power output of VFA-based MFCs when this technology is coupled to a previous bioprocess. In this work, the effect of the degree of reduction of single VFAs on MFC potential was investigated, and a novel acclimation procedure involving the feeding of gradually more complex VFA mixtures is proposed. The power output obtained with butyric acid (6.1 ± 2 mW m−2) was higher than that obtained with propionic acid (5.0 ± 1 mW m−2), as expected based on their degree of reduction. The MFC potential generated by an acetic acid-fed MFC reached 60 mV, but an acetic-butyric acid mixture reduced the cell potential by one order of magnitude. The subsequent addition of propionic acid to the acetic-butyric mixture increased the MFC potential from 1.9 ± 0.1 mV to 35 ± 10 mV in sequential feeding cycles. Consequently, the feeding sequence of acetic, acetic-butyric, and acetic-butyric-propionic acids is proposed as an efficient strategy for the acclimation of MFCs to complex substrates.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. The named "destruction complex" has a critical function in the Wnt/β-catenin pathway regulating the level of β-catenin in the cytoplasm and nucleus. Alterations in this complex lead to the cellular accumulation of β-catenin, which participates in the development and progression of CRC. This study aims to determine the contribution of polymorphisms in the genes of the β-catenin destruction complex to develop CRC, specifically adenomatous polyposis coli (APC) (rs11954856 GT and rs459552 AT), axis inhibition protein 1 (AXIN1) (rs9921222 CT and rs1805105 CT), AXIN2 (rs7224837 AG), and dishevelled 2 (DVL2) (2074222 GA and rs222836 CT). Genomic DNA from 180 sporadic colorectal cancer patients and 150 healthy blood donors were analyzed. The identification of polymorphisms was made by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test. Increased susceptibility to CRC was associated with the polymorphic variants rs11954856 (APC), rs222836 (DVL2), and rs9921222 (AXIN1). Decreased susceptibility was associated with the polymorphisms rs459552 (APC) and 2074222 (DVL2). Association was also observed with advanced Tumor-Node-Metastasis (TNM) stages and tumor location. The haplotypes G-T in APC (rs11954856-rs459552) and A-C in DVL2 (rs2074222-rs222836) were associated with decreased risk of CRC, while the G-T haplotype in the DVL2 gene was associated with increased CRC risk. In conclusion, our results suggest that variants in the destruction complex genes may be involved in the promotion or prevention of colorectal cancer.

Mutations and polymorphisms of the GSK3β gene have been associated with several diseases including Alzheimer disease, diabetes and cancer; however, to date, no variants of this gene have been associated with colorectal cancer (CRC). This study aims to explore, for the first time, the association of the GSK3β rs334558 and rs6438552 polymorphisms with CRC.Genomic DNA from 330 CRC patients and healthy blood donors were analyzed. Identification of polymorphisms was made by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test.Patients carrying the C/T genotype for the rs334558 (TC) polymorphism showed an increased risk for CRC (OR = 1.71, 95% CI: 1.05-2.79, P = 0.039); this association was also observed for TNM stage and tumor location. For the rs6438552 (TC) polymorphism, the OR analysis showed that patients carrying C/T and C/C genotypes have a decreased risk for CRC (OR = 0.44, 95% CI: 0.27-0.70, P = 0.001 and OR = 0.24, 95% CI: 0.10-0.64, P = 0.001, respectively); this decreased risk was also evident in the stratified analysis by TNM stage and tumor location. Haplotype analysis of these 2 loci of GSK3β (rs334558 and rs6438552) showed differential distribution. The T-T and C-C haplotype was associated with a decreased risk of CRC, while the T-C haplotype was associated with an increased risk of CRC.Our results denote that GSK3β gene polymorphisms play a significant role in promoting or preventing CRC. Additionally, variations in this gene are associated with the tumor site and the tumor-node-metastasis (TNM) stage in these patients.

Introduction: Today, scientists accept that the central nervous system of an adult possesses considerable morphological and functional flexibility, allowing it to perform structural remodelling processes even after the individual is fully developed and mature. In addition to the vast number of genes participating in the development of memory, different known epigenetic mechanisms are involved in normal and pathological modifications to neurons and therefore also affect the mechanisms of memory development. Development: This study entailed a systematic review of biomedical article databases in search of genetic and epigenetic factors that participate in synaptic function and memory. Conclusions: The activation of gene expression in response to external stimuli also occurs in differentiated nerve cells. Neural activity induces specific forms of synaptic plasticity that permit the creation and storage of long-term memory. Epigenetic mechanisms play a key role in synaptic modification processes and in the creation and development of memory. Changes in these mechanisms result in the cognitive and memory impairment seen in neurodegenerative diseases (Alzheimer disease, Huntington disease) and in neurodevelopmental disorders (Rett syndrome, fragile X, and schizophrenia). Nevertheless, results obtained from different models are promising and point to potential treatments for some of these diseases. Resumen: Introducción: Hoy en día se acepta que el sistema nervioso central adulto posee una enorme flexibilidad morfofuncional que le permite realizar procesos de remodelación estructural aún después de haber alcanzado su desarrollo y maduración. Además del enorme número de genes que participan en el desarrollo de la memoria, los diferentes mecanismos epigenéticos conocidos también han sido involucrados en procesos de modificación neuronal normal y patológica y, por ende, en los mecanismos de desarrollo de la memoria. Desarrollo: Este trabajo fue llevado a cabo a través de una sistemática revisión de las bases de datos de publicaciones biomédicas sobre los aspectos genéticos y epigenéticos que participan en la función sináptica y la memoria. Conclusiones: La activación de la expresión génica, en respuesta a estímulos extrínsecos, ocurre también en células nerviosas diferenciadas. La actividad neuronal induce formas específicas de plasticidad sináptica que permiten la formación y almacenamiento de la memoria a largo plazo. Los mecanismos epigenéticos tienen un papel crucial en los procesos de modificación sináptica y en la formación y desarrollo de la memoria. Alteraciones en estos mecanismos producen déficit cognitivo y de memoria en padecimientos neurodegenerativos (enfermedad de Alzheimer y Huntington) así como en trastornos del desarrollo neurológico (síndrome de Rett, X-frágil y esquizofrenia). Los resultados obtenidos en diferentes modelos muestran, sin embargo, un escenario promisorio con tratamientos potenciales para algunos de estos padecimientos. Keywords: Epigenetics, Memory, Neural plasticity, Genes and memory, Memory development, Synaptic modification and memory, Palabras clave: Epigenética, Memoria, Plasticidad neuronal, Genes y memoria, Desarrollo de la memoria, Modificación sináptica y memoria

Atypical hemolytic uremic syndrome (aHUS) is a devastating disease characterized by thrombus formation in the microvasculature and is associated with complement dysregulation. The recommended treatment is eculizumab, an humanized monoclonal antibody, which binds complement protein C5 and thereby preventing the assembly of the terminal complement complex (TCC, soluble C5b-9) and the generation of C5a, an anaphylatoxin. The objective of the study was to identify a reliable biomarker, which estimates the degree of complement inactivation under normal and pathophysiological conditions, such as an infection. Here we report on serial measurements of the soluble form of C5b-9, measured in plasma and the TCC capacity (soluble C5b9 after ex-vivo activation, measured in serum) in seven patients with aHUS who were treated with eculizumab. By measuring the latter we were able to assess the maximum possible soluble C5b-9 production under a potent complement trigger. Patients were followed up over a median duration of 3.8 years either on biweekly (q2w) or a three-weekly (q3w) maintenance therapy interval. As expected, eculizumab treatment resulted in a profound decrease of TCC capacity (median 55, IQR 44–88 AU/ml) compared to baseline (1249, 529–1806 AU/ml, p The TCC capacity may represent a novel and easy to perform parameter to determine level of complement inhibition in patients treated with eculizumab, especially because it identifies the residual capacity of inhibition at pathophysiological stages.

Accumulation of bile acids can lead to invalidating pruritus in cholestatic patients. Few reports exist on the influence of lipoprotein-apheresis (LA) on plasma level of total bile acids (tBA). We report of significant decrease in tBA levels and drastic improvement of pruritus in a 5-year-old girl with arthrogryposis-renal failure-cholestasis syndrome. We present LA as a suitable rescue treatment option in therapy-refractory cholestasis-associated pruritus, at least as bridge until a long-term solution such as entero-biliary anastomosis or transplantation is possible.

The small GTPase Rac1 (Ras-related C3 botulinum toxin substrate 1) is commonly overexpressed in cancer and high Rac1 levels are associated with poor patient outcomes in ovarian cancer. Rac1 drives multiple hallmarks of cancer such as proliferation, quiescence, epithelial-to-mesenchymal transition (EMT), and transcriptional programs relevant to tumor development, progression, and chemoresistance. EMT promotes metastatic dissemination, chemoresistance, and cancer stem cell properties. We find that modest overexpression of Rac1 in ovarian tumor cells causes morphologic changes consistent with EMT. Elevated Rac1 (4- fold) expression decreases colony number and increases colony area when compared to vector control cells. In addition, cell invasion through an artificial basement membrane is increased by 10-fold in cells overexpressing Rac1. An increase in mesenchymal markers (e.g., N-cadherin) and decrease in epithelial markers (e.g., E-cadherin) was observed as a consequence of Rac1 expression. Rac1 overexpression was associated with selective upregulation of Slug/Snai2 (8-fold) and Zeb2 (100-fold) mRNA levels with little impact on Snai1, Twist, or Zeb1. Slug/Snai2 expression is reportedly induced by oxidative stress and treatment of six ovarian tumor cell lines with tert-butyl hydroperoxide (TBHP) to generate oxidative stress increased the expression Slug/Snai2, Snai1, and heme oxygenase-1, an indicator of oxidative stress response. This finding confirms that elevated oxidative stress regulates certain EMT transcription factors in various ovarian cancer cells. Rac1 is an essential factor for activation of NADPH oxidases 1, 2, and 3 and generation of reactive oxygen species (ROS). Basal level of ROS was elevated in cells overexpressing Rac1 compared to vector control cells as detected by the fluorescent probe Dihydroethidium (DHE). Similarly, elevated Rac1 increased expression of the oxidative stress response genes heme oxygenase-1 (17-fold) and superoxide dismutase-1 (12-fold), further supporting that Rac1 stimulated ROS signaling in these cells. We further tested the impact of Rac1 inhibition in vivo using R-ketorolac. Analysis of tumor tissue from mice showed decreased expression of heme-oxygenase-1 and Slug/Snai2 in mice treated with R-ketorolac compared to placebo controls. R-ketorolac also decreased invasive implantation and expansion of ovarian cancer xenografts. Taken together, these findings illustrate the functional impact of Rac1 overexpression in ovarian cancer cells and suggest that Rac1 may be a viable target for further drug development to attenuate EMT in ovarian tumors. Citation Format: Martha M. Grimes, Dayna R. Dominquez, Michaela L. Granados, Alejandra Rosales, Melanie Rivera, Angela Wandinger-Ness, Laurie G. Hudson. Rac1 overexpression promotes epithelial-to-mesenchymal transition in ovarian cancer cells [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B59.

Dada la responsabilidad que tiene la hotelería en el consumo de recursos naturales, desde su construcción hasta su funcionamiento y la concienciación que a nivel mundial se viene dando por la conservación ambiental, se han gestado instancias certificadoras que, a través de una serie de indicadores, avalan la sostenibilidad tanto de las instalaciones como de las operaciones y gestión de la actividad hotelera, lo cual se inserta en la visión de la Responsabilidad Social Corporativa (RSC) en la senda de la economía social. El objetivo del presente trabajo es ubicar las prácticas de la hotelería sostenible en el ámbito de la competitividad del sector turístico como ejemplo específico de los agentes de la economía social, partiendo en un primer momento de la vinculación existente entre esta y la RSC, así como la necesaria incorporación de la misma en el turismo a modo de un instrumento competitivo, contexto donde se enmarca la hotelería sostenible como importante integrante del sistema turístico de todo destino y un aporte a la difusión de la argumentación para prácticas responsables. Se concluye que el hotelería sostenible se enmarca en la economía social, por cuanto las ventajas que la misma implica son en beneficio de los propietarios, trabajadores, turistas y las comunidades receptoras; se trata de una puerta de entrada para que el tejido empresarial turístico se incorpore en el modelo de la economía social, no sólo por sus iniciativas respetuosas para con el ambiente natural, social y cultural, sino además por impulsar la incorporación de otras empresas. Given the responsibility of the hotel industry in the consumption of natural resources, from its construction to its operation and the awareness that has been given worldwide for environmental conservation, certifying bodies have been set up, through a series of indicators, guarantee the sustainability of both the facilities and the operations and management of the hotel activity, which is inserted in the vision of Corporate Social Responsibility (CSR) in the path of the social economy. The objective of this work is to locate the practices of the sustainable hotel industry in the field of competitiveness of the tourism sector, as a specific example of the agents of the social economy, starting from the first link between the latter and the CSR. as the necessary incorporation of the same in tourism as a competitive weapon, a context where sustainable hotels are framed, as an important member of the tourist system of all destinations and as a contribution to the dissemination of the argumentation for responsible practices. It is concluded that the sustainable hotel industry is part of the social economy, because the advantages that it implies are for the benefit of the owners, workers, tourists and the host communities; it is a gateway for the tourism business fabric to be incorporated into the social economy model, not only for its respectful initiatives towards the natural, social and cultural environment, but also for encouraging the incorporation of other companies. Este estudo teve como objetivo mostrar a importância do ensino da liderança e da gestão em um contexto de projeto social e de voluntariado. Foi analisada uma escola de liderança e gestão dentro de um Centro de Voluntariado Universitário. A amostra foi composta por 11 pessoas: o coordenador da escola de liderança, quatro professores e seis alunos. As respostas revelaram que os alunos entrevistados receberam uma visão diferente de liderança e demonstraram ser impactados pela abordagem e experiência compartilhada pelos professores. Além disso, os alunos demonstraram maior motivação e vontade de fazer parte de projetos de voluntariado após o programa de liderança. Este artigo pode ser uma contribuição para as associações e universidades, apresentando o poder de desenvolvimento de habilidades de liderança e gestão. À primeira vista, as pessoas podem pensar que apenas os assuntos sociais são relevantes para motivar os voluntários, mas este estudo demonstrou que ensinar as pessoas sobre liderança e gestão pode ser uma fonte significativa de motivação, desempenhando um papel recompensador e oferecendo ferramentas e habilidades para manter os voluntários capacitados para servir os outros.

Aim: In 2016 Baja California went up to the sixth place in incidence of cases from HIV/AIDS. People are getting used to the disease and stopped paying attention to it. To understand this tendency we must determine grade knowledge of the population. Material and methods: Descriptive, transversal and correlative study. 400 people between 17-74 years old were surveyed with an instrument consisting in a polytomous test of 27 items about HIV/AIDS, covering: general knowledge, mechanism of transmission and its prevention. Groups were divided by sex and age: 17-30, 31-45, 46-60, >60 years old. Results were considered sufficient when more than 80% of answers were correct, regular for 60-79%, and deficient if 60 years old. The average age was 31 years. Scholarship: 41.5% (166) were currently bachelor students. 20.75% obtained a degree. 16.7% graduated from high school. The average qualification was 66.9%. Prevention knowledge was very low (26% of answered correctly). 30% showed deficient knowledge. Once correlation tests were made, no statistical relation was found between sex, age and level of knowledge (p= >0.005). Conclusions and Recommendations: Most of general population lack of knowledge, there is too much misinformation about prevention. We recommend more sex education programs at all levels.

As information and services are becoming more and more decentralized and they are often available in the cloud, an increasing number of older adults are expected to use Internet-based services –health, education, finance and others. For this reason, it seems important to plan models and/or strategies to allow the older adult population to acquire and enhance digital competencies more easily. The goal of this research is to show a blended workshop based on a Learning Management System (LMS) as a supporting tool for older adults’ digital literacy. This blended workshop was based on the adoption of an instructional model and on prior experiences of the groups of elderly that participated in the face-to-face workshops. This study involved 98 adults aged 60 and above, 72 Females (68.5 ± 6.9) and 26 Males (73.3 ± 7.4). 61 older adults participated in the face-to-face workshop (FFG) on digital literacy and 37 participated in the blended workshop (BLG). Digital literacy increased at the post-evaluation after the workshops but even more for the BLG. Likewise, in the validation of the blended workshop the results were positive regarding ease of use, perceived usefulness, attitude toward using and intention to use, which showed that older adults believe that it is useful to implement this type of supporting systems for developing their digital competencies. Hence, it is possible to conclude that older adults are capable of learning and acquiring digital literacy skills as long as they are strongly motivated or they know the functional benefits related to ICT.

Online learning play a pivotal role for institutions and universities, because these can support active learning approaches to students. For this reason, it seems important to plan models and / or strategies to allow the older adult population to acquire and enhance digital competencies more easily. This article describes an innovative practice of Blended Learning Supported on a Learning Management System (LMS) whose aim is to enable older people developing digital skills through the using of multimedia teaching materials. The sample of older people was made of 53 Old Females (68 ± 7.61) and 28 Old Males (72.5 ± 7.27). 61 older adults participed in the face-to-face workshop on digital literacy and 20 participed in the blended workshop. Later, a Usability Test was summited to the adults who used the LMS. The results showed that the blended workshop is a very good idea as long as it is used as a support system, because if it were adopted in a totally asynchronous manner, they would have difficulties using it due to lack of assistance.

The increasing human longevity around the world calls for new attention models in which the primary caregiver plays a crucial role as a source of care supply. However, primary caregivers’ lack of training, along with high levels of stress, depression and anxiety, can have a negative impact on both the caregiver’s health and the development of caregiving duties. Hence, the objective of the present article is to introduce the eCuidador platform, an innovative tool that seeks to provide assistance and support to primary caregivers by means of a variety of services available in the cloud with the aim of improving caregivers’ health and quality of life. Likewise, we present the results obtained from the pilot test validation, in which the evaluation of the following parameters was carried out: Usability (12), Functionality (10), Design (11), Usefulness (12) and Satisfaction (12). The participants of this pilot test were 12 primary caregivers (91.66% women).

Context. η Car is one of the most intriguing luminous blue variables in the Galaxy. Observations and models of the X-ray, ultraviolet, optical, and infrared emission suggest a central binary in a highly eccentric orbit with a 5.54 yr period residing in its core. 2D and 3D radiative transfer and hydrodynamic simulations predict a primary with a dense and slow stellar wind that interacts with the faster and lower density wind of the secondary. The wind-wind collision scenario suggests that the secondary’s wind penetrates the primary’s wind creating a low-density cavity in it, with dense walls where the two winds interact. However, the morphology of the cavity and its physical properties are not yet fully constrained. Aims. We aim to trace the inner ∼5–50 au structure of η Car’s wind-wind interaction, as seen through Brγ and, for the first time, through the He I 2s-2p line. Methods. We have used spectro-interferometric observations with the K-band beam-combiner GRAVITY at the VLTI. The analyses of the data include (i) parametrical model-fitting to the interferometric observables, (ii) a CMFGEN model of the source’s spectrum, and (iii) interferometric image reconstruction. Results. Our geometrical modeling of the continuum data allows us to estimate its FWHM angular size close to 2 mas and an elongation ratio ϵ = 1.06 ± 0.05 over a PA = 130° ± 20°. Our CMFGEN modeling of the spectrum helped us to confirm that the role of the secondary should be taken into account to properly reproduce the observed Brγ and He I lines. Chromatic images across the Brγ line reveal a southeast arc-like feature, possibly associated to the hot post-shocked winds flowing along the cavity wall. The images of the He I 2s-2p line served to constrain the 20 mas (∼50 au) structure of the line-emitting region. The observed morphology of He I suggests that the secondary is responsible for the ionized material that produces the line profile. Both the Brγ and the He I 2s-2p maps are consistent with previous hydrodynamical models of the colliding wind scenario. Future dedicated simulations together with an extensive interferometric campaign are necessary to refine our constraints on the wind and stellar parameters of the binary, which finally will help us predict the evolutionary path of η Car.