Differential DNA methylation and CTCF binding between the ESR1 promoter a of MCF-7 and MDA-MB-231 breast cancer cells.

BACKGROUND: ESR1 is expressed by 60-70% of breast tumours. it's a good prognosis factor and the target of hormone therapy. Optimization of ESR1 reactivation therapy is currently ongoing. Here we probe if the transcription factor CTCF plays a role in the differential expression of ESR1 in the breast cancer cell lines MCF-7 (ESR1+) and MDA-MB-231 (ESR1-). METHODS AND RESULTS: Knockdown of CTCF in MCF-7 resulted in decreased ESR1 gene expression. CTCF binds to the promoter of ESR1 in MCF-7 but not in MDA-MB-231 cells. CTCF ESR1 binding sites are unmethylated in MCF7 but methylated in MDA-MB-231 cells. CONCLUSION: ESR1 expression in MCF7 cells is dependent on CTCF expression. CTCF can bind to specific regions of the promotor of ESR1 gene in MCF-7 cells but not in MDA-MB-231 cells, this correlates with the methylation status of these regions and could be involved in the transcriptional regulation of ESR1.

Changes in the Dentate Gyrus Gene Expression Profile Induced by Levetiracetam Treatment in Rats with Mesial Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy. Levetiracetam (LEV) is an antiepileptic drug whose mechanism of action at the genetic level has not been fully described. Therefore, the aim of the present work was to evaluate the relevant gene expression changes in the dentate gyrus (DG) of LEV-treated rats with pilocarpine-induced TLE. Whole-transcriptome microarrays were used to obtain the differential genetic profiles of control (CTRL), epileptic (EPI), and EPI rats treated for one week with LEV (EPI + LEV). Quantitative RT-qPCR was used to evaluate the RNA levels of the genes of interest. According to the results of the EPI vs. CTRL analysis, 685 genes were differentially expressed, 355 of which were underexpressed and 330 of which were overexpressed. According to the analysis of the EPI + LEV vs. EPI groups, 675 genes were differentially expressed, 477 of which were downregulated and 198 of which were upregulated. A total of 94 genes whose expression was altered by epilepsy and modified by LEV were identified. The RT-qPCR confirmed that LEV treatment reversed the increased expression of Hgf mRNA and decreased the expression of the Efcab1, Adam8, Slc24a1, and Serpinb1a genes in the DG. These results indicate that LEV could be involved in nonclassical mechanisms involved in Ca2+ homeostasis and the regulation of the mTOR pathway through Efcab1, Hgf, SLC24a1, Adam8, and Serpinb1a, contributing to reduced hyperexcitability in TLE patients.

Low Expression of BRCA1 as a Potential Relapse Predictor in B-Cell Acute Lymphoblastic Leukemia.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood hematological malignancy worldwide. Treatment outcomes have improved dramatically in recent years; despite this, relapse is still a problem, and the potential molecular explanation for this remains an important field of study. We performed microarray and single-cell RNA-Seq data mining, and we selected significant data with a P -value<0.05. We validated BRCA1 gene expression by means of quantitative (reverse transcription-polymerase chain reaction.) We performed statistical analysis and considered a P -value<0.05 significant. We identified the overexpression of breast cancer 1, early onset (BRCA1; P -value=2.52 -134 ), by means of microarray analysis. Moreover, the normal distribution of BRCA1 expression in healthy bone marrow. In addition, we confirmed the increases in BRCA1 expression using real-time (reverse transcription-polymerase chain reaction and determined that it was significantly reduced in patients with relapse ( P -values=0.026). Finally, we identified that the expression of the BRCA1 gene could predict early relapse ( P -values=0.01). We determined that low expression of BRCA1 was associated with B-cell acute lymphoblastic leukemia relapse and could be a potential molecular prognostic marker.

Transcriptional Regulation of Yin-Yang 1 Expression through the Hypoxia Inducible Factor-1 in Pediatric Acute Lymphoblastic Leukemia.

Yin-Yang transcription factor 1 (YY1) is involved in tumor progression, metastasis and has been shown to be elevated in different cancers, including leukemia. The regulatory mechanism underlying YY1 expression in leukemia is still not understood. Bioinformatics analysis reveal three Hypoxia-inducible factor 1-alpha (HIF-1α) putative binding sites in the YY1 promoter region. The regulation of YY1 by HIF-1α in leukemia was analyzed. Mutation of the putative YY1 binding sites in a reporter system containing the HIF-1α promoter region and CHIP analysis confirmed that these sites are important for YY1 regulation. Leukemia cell lines showed that both proteins HIF-1α and YY1 are co-expressed under hypoxia. In addition, the expression of mRNA of YY1 was increased after 3 h of hypoxia conditions and affect several target genes expression. In contrast, chemical inhibition of HIF-1α induces downregulation of YY1 and sensitizes cells to chemotherapeutic drugs. The clinical implications of HIF-1α in the regulation of YY1 were investigated by evaluation of expression of HIF-1α and YY1 in 108 peripheral blood samples and by RT-PCR in 46 bone marrow samples of patients with pediatric acute lymphoblastic leukemia (ALL). We found that the expression of HIF-1α positively correlates with YY1 expression in those patients. This is consistent with bioinformatic analyses of several databases. Our findings demonstrate for the first time that YY1 can be transcriptionally regulated by HIF-1α, and a correlation between HIF-1α expression and YY1 was found in ALL clinical samples. Hence, HIF-1α and YY1 may be possible therapeutic target and/or biomarkers of ALL.

Hypoxia as a modulator of cytochromes P450: Overexpression of the cytochromes CYP2S1 and CYP24A1 in human liver cancer cells in hypoxia.

Low levels of oxygen (hypoxia) have been reported in solid tumours. This hypoxic microenvironment modulates the expression of genes linked to a more aggressive disease. However, it is unclear if the expression of drug-metabolizing enzymes as cytochromes P450 (CYPs) is affected by hypoxia in cancer. We aimed to define which cytochromes are affected by hypoxia using a liver cancer model in vitro. For this purpose, we assessed whole-genome expression microarrays of HepG2 liver cancer cell line from free repository databases, looking for gene expression hypoxia-associated profiles and selected those cytochromes with significant differences. Then, we corroborated their mRNA expression and protein levels by RT-qPCR and western blot, respectively, as well as immunofluorescence. Based on microarray analysis, we found that the expression of CYP2S1 and CYP24A1 were up-regulated with at least twice fold change compared with normoxia. The levels of mRNA and protein of CYP2S1 and CYP24A1 were increased significantly in hypoxic conditions (P < .05), and this tendency was also observed by immunofluorescence assays. Our data show that the expression of cytochromes CYP2S1 and CYP24A1 are induced in hypoxia, being the first time that CYP24A1 expression is associated with tumour hypoxia; which might have consequences in cancer progression and drug resistance. SIGNIFICANCE OF THE STUDY: Hypoxia is among the most important factors for cellular adaptation to stress. Especially in cancer, a major public health issue, hypoxia plays a substantial role in angiogenesis, metastasis and resistance to therapy. Tumoral hypoxia has been described at least in the brain, breast, cervical, liver, renal, lung, pancreatic and renal cancer. However, the understanding of how hypoxia drives cancer progression is still a major challenge. One emerging question is the role of hypoxia over the expression of drug-metabolizing enzymes, with a significant impact on drug treatment. In this context, our paper focus on the effect of hypoxia on CYPs, which is an essential group of drug-metabolizing enzymes. We show that hypoxia induces the expression of two members of the CYPs family: CYP2S1 and CYP24A1. Importantly, CYP2S1 is a major metabolizer of carcinogenic substances being relevant that hypoxia could promote this function. Interestingly, CYP24A1 limits the action of the active form of vitamin D, which is an anti-proliferative factor in cancer. Our evidence shows for the first time that hypoxia can induce CYP24A1 expression, with a potential effect on cancer progression. Our contribution clarifies a particular effect of tumoral hypoxia and the implications will be useful in the understanding of the progression of cancer, the resistance to treatment and the development of alternative therapies.

Expression of YY1 in pro-B and T phenotypes correlation with poor survival in pediatric acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, constituting 80% of all acute leukemias in minors. Despite the increase in the success of therapies, disease-free survival is over 80% in most cases. For the remaining 20% of patients, new strategies are needed to allow us to know and select those at greatest risk of relapse. We evaluated by immunohistochemistry the expression of the transcription factor YY1 and found that it is overexpressed in peripheral blood leukemia cells of pediatric patients with ALL with Pro-B and T phenotype compared to control samples. Over expression of YY1 was associated with a significantly lower chance of survival. We also evaluated by RT-PCR in bone marrow samples from ALL pediatric patients the association of YY1 expression with the percentage of blasts. High levels of YY1 were present in samples with higher percent of blasts in these patients. In addition, ALL pediatric patients with a poor response to therapy had higher levels at the nuclear level of YY1 than those who responded well to chemotherapy. In conclusion, our data suggest that YY1 could serve in pediatric ALL as markers of evolution and response for this disease, mainly in patients with pro-B and T immunophenotype. It is also suggested that YY1 is implicated in the expanse of blast in these patients.

Multiple-Target Homotopic Quasi-Complete Path Planning Method for Mobile Robot Using a Piecewise Linear Approach.

The ability to plan a multiple-target path that goes through places considered important is desirable for autonomous mobile robots that perform tasks in industrial environments. This characteristic is necessary for inspection robots that monitor the critical conditions of sectors in thermal, nuclear, and hydropower plants. This ability is also useful for applications such as service at home, victim rescue, museum guidance, land mine detection, and so forth. Multiple-target collision-free path planning is a topic that has not been very studied because of the complexity that it implies. Usually, this issue is left in second place because, commonly, it is solved by segmentation using the point-to-point strategy. Nevertheless, this approach exhibits a poor performance, in terms of path length, due to unnecessary turnings and redundant segments present in the found path. In this paper, a multiple-target method based on homotopy continuation capable to calculate a collision-free path in a single execution for complex environments is presented. This method exhibits a better performance, both in speed and efficiency, and robustness compared to the original Homotopic Path Planning Method (HPPM). Among the new schemes that improve their performance are the Double Spherical Tracking (DST), the dummy obstacle scheme, and a systematic criterion to a selection of repulsion parameter. The case studies show its effectiveness to find a solution path for office-like environments in just a few milliseconds, even if they have narrow corridors and hundreds of obstacles. Additionally, a comparison between the proposed method and sampling-based planning algorithms (SBP) with the best performance is presented. Furthermore, the results of case studies show that the proposed method exhibits a better performance than SBP algorithms for execution time, memory, and in some cases path length metrics. Finally, to validate the feasibility of the paths calculated by the proposed planner; two simulations using the pure-pursuit controlled and differential drive robot model contained in the Robotics System Toolbox of MATLAB are presented.

Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and systemic immune-inflammation index in patients with COVID-19-associated pneumonia.

INTRODUCTION: There are hematological parameters that correlate severity and predict mortality mainly in septic and inflammatory states. OBJECTIVE: To correlate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SIII) with COVID-19 severity. METHOD: Descriptive, analytical, retrospective study of patients with COVID-19 pneumonia, in whom NLR, PLR and SIII were analyzed. RESULTS: One-hundred patients were included, 54 men and 46 women, with a mean age of 49.4 ± 19.3 years. NLR, PLR and SIII means were 10.7 ± 10.9, 290.1 ± 229.2, and 2.6 ± 3.4 x 109, respectively. In 54 %, pneumonia was mild, and in 46 %, severe. Regarding hospital outcomes, 75 % were discharged due to improvement and 25 % died. NLR, PLR and SIII means of the patients who died versus the patients who improved were 20.4 ± 16.9 versus 7.5 ± 4.9 (p = 0.001), 417.1 ± 379.7 versus 247.7 ± 127.4 (p = 0.038) and 4.8 ± 6.1 versus 1.9 ± 1.2 × 109 (p = 0.030), respectively. CONCLUSION: Hematological parameters can be used in patients with COVID-19-associated pneumonia as predictors of severity and prognosis. INTRODUCCIÓN: Existen índices hematológicos que correlacionan la severidad y predicen la mortalidad, principalmente en ­estados sépticos y de inflamación. OBJETIVO: Correlacionar los índices neutrófilo/linfocito (INL), plaqueta/linfocito (IPL) e inmunidad/inflamación sistémica (IIIS) con la severidad de COVID-19. MÉTODO: Estudio descriptivo, analítico y retrospectivo de pacientes con neumonía por COVID-19, en quienes se analizaron INL, IPL e IIIS. RESULTADOS: Se incluyeron 100 pacientes, 54 hombres y 46 mujeres, con una media de 49.4 ± 19.3 años. Las medias de INL, IPL e IIIS fueron 10.7 ± 10.9, 290.1 ± 229.2 y 2.6 ± 3.4 × 109, respectivamente. En 54 %, la neumonía fue leve y en 46 %, grave. En cuanto a los desenlaces hospitalarios, 75 % egresó por mejoría y 25 % falleció. Las medias de INL, IPL e IIIS de los pacientes que fallecieron versus las de los pacientes que mejoraron fueron 20.4 ± 16.9 versus 7.5 ± 4.9 (p = 0.001), 417.1 ± 379.7 versus 247.7 ± 127.4 (p = 0.038) y 4.8 ± 6.1 versus 1.9 ± 1.2 × 109 (p = 0.030), respectivamente. CONCLUSIÓN: Los índices hematológicos en pacientes con neumonía por COVID-19 pueden ser empleados como predictores de severidad y pronóstico.

Stereoselective Synthesis of Highly Substituted Tetrahydropyrans through an Evans Aldol-Prins Strategy.

A direct and general method for the synthesis of naturally occurring 2,3,4,5,6-pentasubstituted tetrahydropyrans has been developed, employing ß,γ-unsaturated N-acyl oxazolidin-2-ones as key starting materials. The combination of the Evans aldol addition and the Prins cyclization allowed the diastereoselective and efficient generation of the desired oxacycles in two fashions: a one-pot Evans aldol-Prins protocol, in which five new σ bonds and five contiguous stereocenters were straightforwardly generated, and a two-step version, which additionally permitted the isolation of ß,γ-unsaturated alcohol precursors bearing an N-acyl oxazolidin-2-one in the α position. From these alcohols were also obtained halogenated pentasubstituted tetrahydropyrans as well as 2,3,4,5-tetrasubstituted tetrahydrofurans, shedding light on the mechanism of the process. Computational studies were consistent with the experimental findings, and this innovative Evans aldol-Prins strategy was performed for the preparation of a battery of more than 30 densely substituted tetrahydropyrans, unprecedentedly fused to a 1,3-oxazinane-2,4-dione ring, both in a racemic fashion and in an enantiomeric fashion. These novel molecules were successfully submitted to several transformations to permit simple access to a variety of differently functionalized tetrahydropyrans. Most of these unique molecules were evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria and the yeast Candida albicans, and some structure-activity relationships were established.

One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters.

An improved protocol for the synthesis of enantiomerically pure allylic amines is reported. N-Protected α-amino esters derived from natural amino acids were submitted to a one-pot tandem reduction-olefination process. The sequential reduction with DIBAL-H at -78 °C and subsequent in situ addition of organophosphorus reagents yielded the corresponding allylic amines without the need to isolate the intermediate aldehyde. This circumvents the problem of instability of the aldehydes. The method tolerates well both Wittig and Horner-Wadsworth-Emmons organophosphorus reagents. A better Z-(dia)stereoselectivity was observed when compared to the previous one-pot method. The (dia)stereoselectivity of the process was affected neither by the reaction solvent nor by the amount of DIBAL-H employed. The method is compatible with the presence of free hydroxy groups as shown with serine and threonine derivatives.

Oxasqualenoids from Laurencia viridis: Combined Spectroscopic-Computational Analysis and Antifouling Potential.

The chemical study of the red alga Laurencia viridis has led to the isolation of four new polyether triterpenoids: 28-hydroxysaiyacenol B (2), saiyacenol C (3), 15,16-epoxythyrsiferol A (4), and 15,16-epoxythyrsiferol B (5). The structures of 2 and 3 were established mainly by NMR data analysis and comparison with the well-known metabolite dehydrothyrsiferol (1). However, due to the existence of a nonprotonated carbon within the epoxide functionality, stereochemical assignments in 4 and 5 required an in-depth structural study that included NOESY data, J-based configuration analysis, comparison with synthetic models, and DFT calculations. The biological activities of the new metabolites and other related oxasqualenoids were evaluated for the first time against a panel of relevant biofouling marine organisms, and structure-activity conclusions were obtained.

Tracking anthropogenic microparticles in wildlife of an alpine insular environment.

Despite the isolation of remote natural regions, it has been discovered that they are experiencing the accumulation of anthropogenic microparticles (i.e., microplastics or natural or semisynthetic cellulosic particles). Teide National Park (Canary Islands, Spain) is a high-mountain protected area known for its rich biodiversity. This study aims to assess the occurrence of coloured anthropogenic particles in the faecal matter of wild mammals, specifically rabbits and mouflons, residing in the park. With this purpose, faeces were collected from 68 systematically distributed sampling points. A stereomicroscopy-guided grinding process allowed a chemical-free and quick visual inspection of 616 individual excreta, revealing that 96% were particle-free. However, 37 anthropogenic particles were found, which correspond to 0.79 ± 0.20 items per gram of dry faecal matter. The archetypical particle was a cellulosic blue microfibre of 2721 ± 407 µm, though poly(ethylene-vinyl acetate) and polypropylene were also identified via micro Fourier-transform infrared spectroscopic analysis. Atmospheric deposition and touristic pressure may be the sources of the anthropogenic particles, as they were randomly found in 36% of the sampling points. These findings represent the first evidence of anthropogenic particle ingestion by wild rabbits and mouflons, signifying the introduction of microplastics into terrestrial food chains in a remote high-mountain environment.

Cooperative effects of Janus and Aurora kinase inhibition by CEP701 in cells expressing Jak2V617F.

The Janus kinase 2 mutant V617F occurs with high frequency in myeloproliferative neoplasms. Further mutations affecting the Janus kinase family have been discovered mostly in leukaemias and in myeloproliferative neoplasms. Owing to their involvement in neoplasia, inflammatory diseases and in the immune response, Janus kinases are promising targets for kinase inhibitor therapy in these disease settings. Various quantitative assays including two newly developed screening assays were used to characterize the function of different small-molecule compounds in cells expressing Jak2V617F. A detailed comparative analysis of different Janus kinase inhibitors in our quantitative assays and the subsequent characterization of additional activities demonstrated for the first time that the most potent Jak2 inhibitor in our study, CEP701, also targets Aurora kinases. CEP701 shows a unique combination of both activities which is not found in other compounds also targeting Jak2. Furthermore, colony forming cell assays showed that Janus kinase 2 inhibitors preferentially suppressed the growth of erythroid colonies, whereas inhibitors of Aurora kinases preferentially blocked myeloid colony growth. CEP701 demonstrated a combined suppression of both colony types. Moreover, we show that combined application of a Janus and an Aurora kinase inhibitor recapitulated the effect observed for CEP701 but might allow for more flexibility in combining both activities in clinical settings, e.g. in the treatment of myeloproliferative neoplasms. The newly developed screening assays are high throughput compatible and allow an easy detection of new compounds with Janus kinase 2 inhibitory activity.

Anaerobic digestion of commercial PLA and PBAT biodegradable plastic bags: Potential biogas production and 1H NMR and ATR-FTIR assessed biodegradation.

Bioplastics aim to substitute conventional plastics in most applications, a critical one being the collection of organic wastes for composting or anaerobic degradation. The anaerobic biodegradability of six commercial bags composed of PBAT or PLA/PBAT blends and certified as compostable [1] was studied using 1H NMR and ATR-FTIR techniques. This study aims to elucidate if commercial bioplastic bags are biodegradable under conventional conditions found in anaerobic digestates. Results showed that all studied bags are hardly anaerobically biodegradable at mesophilic temperatures. The biogas yield resulting from the anaerobic digestion under laboratory conditions oscillated between 270.3 ± 45.5 L kgVS-1 for a trash bag composed of 26.64 ± 0.03%/73.36 ± 0.03% PLA/PBAT and 36.7 ± 25.0 L kgVS-1 for a bag composed of 21.24 ± 0.08%/78.76 ± 0.08% PLA/PBAT. The degree of biodegradation did not correlate with PLA/PBAT molar composition. However, 1H NMR characterization showed that the anaerobic biodegradation occurred mostly in the PLA fraction. No bioplastics biodegradation products were detected in the digestate fraction (<2 mm). Finally, none of the biodegraded bags comply with the EN 13432 standard.

Nanoplastics in the soil environment: Analytical methods, occurrence, fate and ecological implications.

Soils play a very important role in ecosystems sustainability, either natural or agricultural ones, serving as an essential support for living organisms of different kinds. However, in the current context of extremely high plastic pollution, soils are highly threatened. Plastics can change the chemical and physical properties of the soils and may also affect the biota. Of particular importance is the fact that plastics can be fragmented into microplastics and, to a final extent into nanoplastics. Due to their extremely low size and high surface area, nanoplastics may even have a higher impact in soil ecosystems. Their transport through the edaphic environment is regulated by the physicochemical properties of the soil and plastic particles themselves, anthropic activities and biota interactions. Their degradation in soils is associated with a series of mechanical, photo-, thermo-, and bio-mediated transformations eventually conducive to their mineralisation. Their tiny size is precisely the main setback when it comes to sampling soils and subsequent processes for their identification and quantification, albeit pyrolysis coupled with gas chromatography-mass spectrometry and other spectroscopic techniques have proven to be useful for their analysis. Another issue as a consequence of their minuscule size lies in their uptake by plants roots and their ingestion by soil dwelling fauna, producing morphological deformations, damage to organs and physiological malfunctions, as well as the risks associated to their entrance in the food chain, although current conclusions are not always consistent and show the same pattern of effects. Thus, given the omnipresence and seriousness of the plastic menace, this review article pretends to provide a general overview of the most recent data available regarding nanoplastics determination, occurrence, fate and effects in soils, with special emphasis on their ecological implications.

Catastrophic antiphospholipid syndrome in Mexico. Literature review.

Catastrophic antiphospholipid syndrome (CAPS) is a rare entity, approximately 600 cases have been reported around the world, and the prevalence in Mexico is unknown. OBJECTIVE: To determine the estimated prevalence of CAPS in Mexico. MATERIAL AND METHODS: A literature search of isolated clinical cases or case series was conducted in diverse search engines, using the terms: "Catastrophic Antiphospholipid Syndrome" and "Mexico" in May 2022. RESULTS: We found a series of retrospective cases in autopsies that included 12 cases, two reports that included 2 cases each, and reports of 11 isolated clinical cases; these publications were generated between 2003 and 2020. In total, we collected data on 27 cases of CAPS, of which 16 correspond to primary antiphospholipid syndrome, 10 are associated with systemic lupus erythematosus, and 1 case corresponds to systemic sclerosis. The estimated prevalence rate in the Mexican population in 2022 is 2 cases per 10,000,000 inhabitants. The estimated mortality was 68% in this case series. CONCLUSION: Cases of catastrophic antiphospholipid syndrome in Mexico are underreported; identifying them will help improve current diagnostic and therapeutic strategies used in the country, encouraging the implementation of triple therapy and, in refractory cases, the use of eculizumab, to reduce current mortality.

Female gout: age and duration of the disease determine clinical presentation.

OBJECTIVE: This study aimed to compare data and associated diseases between women and men with gout paired for age and duration of the disease. METHODS: Consecutive patients from outpatient gout clinics of 2 rheumatology departments were included in this case-control study. We identified 37 women with gout diagnosis and paired them by age and duration of the disease with 37 men with gout (American College of Rheumatology criteria). Variables were clinical data, associated diseases, and renal function evaluated by 3 methods: creatinine clearance, modification of diet in renal disease, and Cockcroft-Gault. RESULTS: Mean (SD) age was 54.47 (15.13) years in women versus 53.52 (15.23) years in males, and mean (SD) age at onset 46.77 (16.63) years versus 45.62 (16.16) years in women and men, respectively. Hypertension was found in 26 (73%) of 37 women and in 27 (70%) of 37 men, previous diuretics was found in only 1 man, and no significant differences were found between women and men in gout or associated metabolic diseases. Females had lower creatinine clearance than males did (49.8 [29.7] vs. 67.1 [35.5] mL/min, P = 0.039). But, when it was calculated by methods considering sex, there were no significant differences (Cockcroft-Gault 66.4 [37.6] vs. 78.8 [43.8] mL/min [P = 0.2] and modification of diet in renal disease 73.8 [64.6] vs. 73.1 [35.0] mL/min [P = 0.9], females vs. males, respectively). Thirteen women (35%) were premenopausal at onset, 2 had familial history of gout, and 2 had history of lithiasis; other variables were not different from postmenopausal women. CONCLUSIONS: Factors previously associated to female gout seem to be more related to age than to sex or to the disease itself. In our country, patients with gout (males and females) are younger at onset. Gender should be considered to evaluate renal function in females with gout. One third of our female patients with gout were premenopausal and had unexpected higher frequency of lithiasis; no other differences with postmenopausal women were found.

Data-Driven Real-Time Magnetic Tracking Applied to Myokinetic Interfaces.

A new concept of human-machine interface to control hand prostheses based on displacements of multiple magnets implanted in the limb residual muscles, the myokinetic control interface, has been recently proposed. In previous works, magnets localization has been achieved following an optimization procedure to find an approximate solution to an analytical model. To simplify and speed up the localization problem, here we employ machine learning models, namely linear and radial basis functions artificial neural networks, which can translate measured magnetic information to desired commands for active prosthetic devices. They were developed offline and then implemented on field-programmable gate arrays using customized floating-point operators. We optimized computational precision, execution time, hardware, and energy consumption, as they are essential features in the context of wearable devices. When used to track a single magnet in a mockup of the human forearm, the proposed data-driven strategy achieved a tracking accuracy of 720 µm 95% of the time and latency of 12.07 µs. The proposed system architecture is expected to be more power-efficient compared to previous solutions. The outcomes of this work encourage further research on improving the devised methods to deal with multiple magnets simultaneously.

Arbovirus vectors in municipalities with a high risk of dengue in Cauca, Southwestern Colombia.

The Culicidae family has two of the most important disease vector genus: Aedes spp. and Culex spp. Both of these are involved in the transmission of arboviruses. Here, we provide novel data for the geographical distribution of 2,383 specimens in the Culicidae family. We also report the percentage of houses infested with these vectors, and Shannon and Simpson diversity indices in three municipalities located in Cauca, Colombia. This dataset is relevant for research on vector-borne diseases because Aedes spp. can transmit arboviruses such as dengue, Zika and chikungunya, and Culex spp. is a well-known vector of West Nile virus and Venezuelan equine encephalitis.

The Proliferating Cell Nuclear Antigen (PCNA) Transcript Variants as Potential Relapse Markers in B-Cell Acute Lymphoblastic Leukemia.

Leukemia is the most common childhood malignancy in Mexico, representing more than 50% of all childhood cancers. Although treatment leads to a survival of up to 90% in developing countries, in our country, it is less than 65%. Additionally, ~30% of patients relapse with poor prognosis. Alternative splicing plays an important role in transcriptome diversity and cellular biology. This mechanism promotes an increase in the assortment of proteins with potentially distinct functions from a single gene. The proliferating cell nuclear antigen (PCNA) gene encodes two transcripts for the same protein of 261 amino acids, which is associated with several important cellular processes and with several types of cancer. However, the diversity of the transcript variants expressed in this condition is not clear. Then, we used microarray gene expression to identify changes in the exon expression level of PCNA. The data were validated using RT-PCR and Sanger sequencing, and three additional transcripts (PCNA_V3, PCNA_V4, and PCNA_V5) were identified. Computational analyses were used to determine the potential proteins resulting, their structure, and interactions with PCNA native protein and themselves. Additionally, the PCNA transcript variants were inhibited using specific siRNA, determining that their inhibition contributes to the malignant characteristics in vitro. Finally, we quantified the PCNA transcript variants in acute lymphoblastic leukemia samples and identified their expression in this disease. Based on the clinical characteristics, we determined that PCNA_V2 and PCNA_V4 are expressed at significantly low levels in relapsed B-ALL patients. We conclude that the low expression of PCNA_V2 and PCNA_V4 could be a potential molecular marker of relapse in acute lymphoblastic leukemia patients.