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Pesticide exposure is a risk factor for the development of several diseases, including breast cancer (BC). The enzyme UGT2B7 participate in detoxification of pesticides and the presence rs7438135 (G > A) variant in your gene increases its glucuronidation potential, contributing to oxidative stress metabolites neutralization. Here we investigated the impact of occupational pesticide exposure on the systemic oxidative stress generation from 228 women with BC depending on their UGT2B7 rs7438135 (G > A) status. q-PCR investigated the presence of the rs7438135 variant, and oxidative stress markers (lipid peroxidation levels, total antioxidant capacity-TRAP, and nitric oxide metabolites-NOx) were measured in plasma. Pesticide exposure induced significant augment in the systemic lipid peroxidation in the presence of the variant for several clinicopathological conditions, including tumors with high proliferation index (ki67) and with high aggressiveness. NOx was augmented in high ki67, positive progesterone receptors, high-grade and triple-negative/Luminal B tumors, and low-risk stratified patients. TRAP was depleted in young patients at menopause and those with triple-negative/Luminal B tumors, as well as those stratified as at low risk for death and recurrence. These findings showed that the presence of the variant was not able to protect from pesticide-induced oxidative stress generation in BC patients.

Asunto(s)

Neoplasias de la Mama , Glucuronosiltransferasa , Estrés Oxidativo , Plaguicidas , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Estrés Oxidativo/efectos de los fármacos , Plaguicidas/toxicidad , Persona de Mediana Edad , Glucuronosiltransferasa/genética , Glucuronosiltransferasa/metabolismo , Adulto , Pronóstico , Exposición Profesional/efectos adversos , Anciano , Alelos , Peroxidación de Lípido/efectos de los fármacos , Polimorfismo de Nucleótido Simple

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Major Depressive Disorder (MDD) is one of the most prevalent neurobiological disorders globally. Antidepressant medications are the first-line treatment for managing symptoms. However, over time, pharmacotherapy has been linked to several challenges, primarily due to the wide array of side effects that often reduce patient adherence to treatment. The literature suggests that these side effects may be influenced by polymorphisms in genes related to the pharmacokinetics and pharmacodynamics of antidepressants. Thus, this systematic review aimed to identify studies that investigated the association between genetic variants and side effects resulting from antidepressant treatment in individuals with MDD. Original articles indexed in the electronic databases Cochrane Library, EMBASE, MEDLINE via PubMed, and Scopus were identified. A total of 55 studies were included in the review, and data regarding the outcomes of interest were extracted. Due to the exploratory nature of the review, a narrative/descriptive synthesis of the results was performed. The risk of bias was evaluated using the Joanna Briggs Institute's tools, tailored to the design of each study. Polymorphisms in 35 genes were statistically associated with the development of side effects. A subsequent Protein-Protein Interaction Network analysis helped elucidate the key biological pathways involved in antidepressant side effects, with a view toward exploring the potential application of pharmacogenetic markers in clinical practice.

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OBJECTIVE: To make evidence-based recommendations for the treatment of Single-Sided Deafness (SSD) in children and adults. METHODS: Task force members were instructed on knowledge synthesis methods, including electronic database search, review and selection of relevant citations, and critical appraisal of selected studies. Articles written in English or Portuguese on SSD were eligible for inclusion. The American College of Physicians' guideline grading system and the American Thyroid Association's guideline criteria were used for critical appraisal of evidence and recommendations for therapeutic interventions. RESULTS: The topics were divided into 3 parts: (1) Impact of SSD in children; (2) Impact of SSD in adults; and (3) SSD in patients with temporal bone tumors. CONCLUSIONS: Decision-making for patients with SSD is complex and multifactorial. The lack of consensus on the quality of outcomes and on which measurement tools to use hinders a proper comparison of different treatment options. Contralateral routing of signal hearing aids and bone conduction devices can alleviate the head shadow effect and improve sound awareness and signal-to-noise ratio in the affected ear. However, they cannot restore binaural hearing. Cochlear implants can restore binaural hearing, producing significant improvements in speech perception, spatial localization of sound, tinnitus control, and overall quality of life. However, cochlear implantation is not recommended in cases of cochlear nerve deficiency, a relatively common cause of congenital SSD.

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Monolayer transition metal dichalcogenides (TMDs) have emerged as promising materials to generate single-photon emitters (SPEs). While there are several previous reports in the literature about TMD-based SPEs, the precise nature of the excitonic states involved in them is still under debate. Here, we use magneto-optical techniques under in-plane and out-of-plane magnetic fields to investigate the nature of SPEs in WSe2 monolayers on glass substrates under different strain profiles. Our results reveal important changes on the exciton localization and, consequently, on the optical properties of SPEs. Remarkably, we observe an anomalous PL energy redshift with no significant changes of photoluminescence (PL) intensity under an in-plane magnetic field. We present a model to explain this redshift based on intervalley defect excitons under a parallel magnetic field. Overall, our results offer important insights into the nature of SPEs in TMDs, which are valuable for future applications in quantum technologies.

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Introduction: Genetic polymorphisms who disturb the mineral homeostasis during tooth development and eruption are candidate to clarify the molecular mechanisms involved in changes in the tooth eruption chronology. In this study, we evaluate whether the FokI (rs2228570) and BglI (rs739837) polymorphisms in the Vitamin D receptor (VDR) gene are associated with changes in the chronology of eruption of permanent teeth. Material & method: This cross-sectional study randomly included 353 biologically unrelated children, both sexes, without systemic impairment or syndromes and history of trauma during the primary dentition. One operator perform the oral clinical examination. The tooth was considered erupted if there was a visible minimum of any tooth surface emerging from the mucosa. Genomic DNA was extracted from buccal epithelial cells from saliva samples. Genotyping was performed by Real-Time Polymerase Chain Reactions using TaqMan® technology. The average of the total number of erupted permanent teeth between the genotypes was compared by the Mann-Whitney test and multivariate Generalized Linear Models (GLM) (α = 5 %). ß values with Confidence Interval (CI) 95 % were calculated. Results: The heterozygous adenine-guanine genotype of the FokI significantly decreases the number of erupted permanent teeth (ß = -1.15; CI 95 % = -2.22 to -0.07; p = 0.036). In the stratified analysis for maxillary and mandibular teeth, this genotype was associated with a decrease in the number of erupted maxillary permanent teeth (ß = -0.65; CI 95 % = -1.22 to -0.09; p = 0.023). BglI was not associated with permanent teeth eruption. Conclusion: The FokI, but not BglI, in the VDR may delay the eruption of permanent teeth.

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Introduction: The Cuban population is genetically diverse, and information on the prevalence of genetic variants is still limited. As complex admixture processes have occurred, we hypothesized that the frequency of pharmacogenetic variants and drug responses may vary within the country. The aims of the study were to describe the frequency distribution of 43 single-nucleotide variants (SNVs) from 25 genes of pharmacogenetic interest within the Cuba population and in relation to other populations, while taking into consideration some descriptive variables such as place of birth and skin color. Materials and Methods: SNVs were analyzed in 357 unrelated healthy Cuban volunteers. Genotype, allele frequencies, and ancestry proportions were determined, and the pairwise fixation index (FST ) was evaluated. Results: Hardy-Weinberg equilibrium (HWE) deviations in six loci (rs11572103, rs2740574, rs776746, rs3025039, rs861539, and rs1762429) were identified. Minor allele frequencies (MAFs) ranged from 0.00 to 0.15 for variants in genes encoding xenobiotic metabolizing enzymes. They also ranged from 0.01 to 0.21 for variants in DNA repair, growth factors, methyltransferase, and methyl-binding proteins, while they ranged from 0.04 to 0.27 for variants in the O-6-methylguanine-DNA methyltransferase enzyme. Moderate genetic divergence was observed upon comparison to Africans (FST = 0.071 and SD 0.079), with 19 markers exhibiting moderate-to-large genetic differentiation. The average European, African, and Amerindian ancestry proportions were 67.8%, 27.2%, and 5.3%, respectively. Ancestry proportions differed by skin color and birthplace for both African and European components, with the exception of the European component, which showed no significant difference between individuals from Western and Eastern regions. Meanwhile, the statistical significance varied in comparisons by skin color and birthplace within the Amerindian component. Low genetic divergence was observed across geographical regions. We identified 12 variants showing moderate-to-large differentiation between White/Black individuals. Conclusion: Altogether, our results may support national strategies for the introduction of pharmacogenetic tools in clinical practice, contributing to the development of precision medicine in Cuba.

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Recently, a single-neuron degeneration model has been proposed to understand the development of idiopathic Parkinson's disease based on (i) the extremely slow development of the degenerative process before the onset of motor symptoms and during the progression of the disease and (ii) the fact that it is triggered by an endogenous neurotoxin that does not have an expansive character, limiting its neurotoxic effect to single neuromelanin-containing dopaminergic neurons. It has been proposed that aminochrome is the endogenous neurotoxin that triggers the neurodegenerative process in idiopathic Parkinson's disease by triggering mitochondrial dysfunction, oxidative stress, neuroinflammation, dysfunction of both lysosomal and proteasomal protein degradation, endoplasmic reticulum stress and formation of neurotoxic alpha-synuclein oligomers. Aminochrome is an endogenous neurotoxin that is rapidly reduced by flavoenzymes and/or forms adducts with proteins, which implies that it is impossible for it to have a propagative neurotoxic effect on neighboring neurons. Interestingly, the enzymes DT-diaphorase and glutathione transferase M2-2 prevent the neurotoxic effects of aminochrome. Natural compounds present in fruits, vegetables and other plant products have been shown to activate the KEAP1/Nrf2 signaling pathway by increasing the expression of antioxidant enzymes including DT-diaphorase and glutathione transferase. This review analyzes the possibility of searching for natural compounds that increase the expression of DT-diaphorase and glutathione transferase through activation of the KEAP1/Nrf2 signaling pathway.

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Acute lymphoblastic leukemia represents the most prevalent childhood cancer. Modern chemotherapy has significantly improved outcomes, achieving EFS rates of 80% and OS rates nearing 90% in developed nations, while in developing regions, rates remain below 50%, highlighting disparities, and this difference is due to several factors. Genetic variability plays a role in these drug response disparities, presenting single-nucleotide variations (SNVs). Pharmacogenetic research aims to pinpoint these SNVs early in treatment to predict specific drug responses effectively. This review aims to explore advancements in pharmacogenetics associated with asparaginase (ASNase). ASNase plays a crucial role in the treatment of ALL and is available in three formulations: E. coli, Erwinia, and PEG ASNase. ASNase therapy presents challenges due to adverse effects, like hypersensitivity reactions. Identifying predictive markers for hypersensitivity development beforehand is crucial for optimizing treatments. Several pharmacogenetic studies have investigated the association between SNVs and the risk of hypersensitivity. Key genes include GRIA1, NFATC2, CNTO3, ARHGAP28, MYBBP1A, and HLA. Studies have highlighted associations between SNVs within these genes and hypersensitivity reactions. Notably, most pharmacogenetic investigations of hypersensitivity have focused on patients treated with E. coli, emphasizing the need for broader exploration across different formulations. Future research investigating these variants holds promise for advancing our understanding of ASNase's pharmacogenetics.

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Exploring genetic resources through genomic analyses has emerged as a powerful strategy to develop common bean (Phaseolus vulgaris L.) cultivars that are both productive and well-adapted to various environments. This study aimed to identify genomic regions linked to morpho-agronomic traits in Mesoamerican and Andean common bean accessions and to elucidate the proteins potentially involved in these traits. We evaluated 109 common bean accessions over three agricultural years, focusing on traits including the grain yield (YDSD), 100-seed weight (SW), number of seeds per pod (SDPD), number of pods per plant (PDPL), first pod insertion height (FPIH), plant height (PLHT), days to flowering (DF), and days to maturity (DPM). Using multilocus methods such as mrMLM, FASTmrMLM, FASTmrEMMA, ISIS EM-BLASSO, and pLARmEB, we identified 36 significant SNPs across all chromosomes (Pv01 to Pv11). Validating these SNPs and candidate genes in segregating populations is crucial for developing more productive common bean cultivars through marker-assisted selection.

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OBJECTIVE: The aim of the present study was to determine the cost-utility of single inhaler combination inhaled corticosteroid and a long-acting ß2-agonist (ICS/LABAs) as both maintenance and reliever (SMART) compared with a step-up maintenance treatment with a fixed medium to high dose of ICS combined with LABA and a short-acting ß2-agonist (SABA) as reliever (ICS-LABA maintenance plus SABA) among patients aged 12 years or more with poorly controlled asthma in Colombia. METHODS: A Markov-type model was developed to estimate the costs and health outcomes of a simulated cohort of patients aged 12 years or more with uncontrolled asthma treated for 12 months. The main effectiveness data were obtained from a recent meta-analysis. The main outcome was the variable ''quality-adjusted life-years'' (QALYs). RESULTS: The base-case analysis showed that the budesonide/formoterol (BUD/FORM) SMART strategy was associated with lower overall treatment costs (US $3,062.37 vs. $4,462.02 average cost per patient over 12 months) and the greatest gain in QALYs (0.8511 vs. 0.8258 QALYs on average per patient over 12 months) compared with ICS-LABA maintenance plus SABA at step 4, thus leading to dominance. CONCLUSIONS: In patients aged 12 years or more with uncontrolled asthma at GINA step 3 or 4, the BUD/FORM SMART strategy at either step 3 or 4 is cost-effective compared with the ICS-LABA maintenance plus SABA at step 4 strategy, because it shows a greater gain in QALYs at lower total treatment costs.

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OBJECTIVE: The aim of this study was to construct a prognostic model based on the TP53 mutation to calculate prognostic risk scores of patients with HPSCC. METHODS: TP53 mutation and transcriptome data were downloaded from the TCGA databases. Gene expression data from GSE65858, GSE41613, GSE3292, GSE31056, GSE39366, and GSE227156 datasets were downloaded from the GEO database. GSEA, univariate, multivariate Cox analyses, and LASSO analysis were employed to identify key genes and construct the prognostic model. ROC curves were utilized to validate the OS and RFS results obtained from the model. The associations between risk scores with various clinicopathological characteristics and immune scores were analyzed via ggplot2, corrplot package, and GSVA, respectively. Single-cell sequencing data was analyzed via unbiased clustering and SingleR cell annotations. RESULTS: Initially, two key genes, POLD2 and POLR2G, were identified and utilized to construct the prognostic model. Samples were divided into different risk groups via the risk scores obtained from the model, with high-risk group samples exhibiting poorer prognosis. Furthermore, the risk score exhibited a positive correlation with lymphatic metastasis in patients and the immune scores of CD4+ T, CD8+ T, dendritic cell, macrophage, and neutrophil. The immune responses also exhibited notable disparities between the high- and low-risk groups. The results of single-cell sequencing analysis demonstrated that epithelial cells and macrophages were relatively abundant in HPSCC samples. POLD2 and POLR2G exhibited higher expressions in epithelial cells, with most of the identified pathways also enriched in epithelial cells. CONCLUSION: The prognostic model exhibited a significant capacity for predicting the prognosis of HSPCC samples based on the TP53 mutation conditions and may also predict the cancer characteristics and immune infiltration scores of samples via different risk scores obtained from the model. LEVEL OF EVIDENCE: Level 5.

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To further understand the impact of deficiency of the autoimmune regulator (Aire) gene during the adhesion of medullary thymic epithelial cells (mTECs) to thymocytes, we sequenced single-cell libraries (scRNA-seq) obtained from Aire wild-type (WT) (Airewt/wt ) or Aire-deficient (Airewt/mut ) mTECs cocultured with WT single-positive (SP) CD4+ thymocytes. Although the libraries differed in their mRNA and long noncoding RNA (lncRNA) profiles, indicating that mTECs were heterogeneous in terms of their transcriptome, UMAP clustering revealed that both mTEC lines expressed their specific markers, i.e., Epcam, Itgb4, Itga6, and Casp3 in resting mTECs and Ccna2, Pbk, and Birc5 in proliferative mTECs. Both cocultured SP CD4+ thymocytes remained in a homogeneous cluster expressing the Il7r and Ccr7 markers. Comparisons of the two types of cocultures revealed the differential expression of mRNAs that encode transcription factors (Zfpm2, Satb1, and Lef1), cell adhesion genes (Itgb1) in mTECs, and Themis in thymocytes, which is associated with the regulation of positive and negative selection. At the single-cell sequencing resolution, we observed that Aire acts on both Aire WT and Aire-deficient mTECs as an upstream controller of mRNAs, which encode transcription factors or adhesion proteins that, in turn, are posttranscriptionally controlled by lncRNAs, for example, Neat1, Malat1, Pvt1, and Dancr among others. Under Aire deficiency, mTECs dysregulate the expression of MHC-II, CD80, and CD326 (EPCAM) protein markers as well as metabolism and cell cycle-related mRNAs, which delay the cell cycle progression. Moreover, when adhered to mTECs, WT SP CD4+ or CD8+ thymocytes modulate the expression of cell activation proteins, including CD28 and CD152/CTLA4, and the expression of cellular metabolism mRNAs. These findings indicate a complex mechanism through which an imbalance in Aire expression can affect mTECs and thymocytes during adhesion.

Asunto(s)

Proteína AIRE , Adhesión Celular , Células Epiteliales , ARN Largo no Codificante , Timocitos , Factores de Transcripción , Transcriptoma , ARN Largo no Codificante/genética , Animales , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ratones , Timocitos/metabolismo , Timocitos/inmunología , Timocitos/citología , Células Epiteliales/metabolismo , Células Epiteliales/inmunología , Timo/citología , Timo/inmunología , Timo/metabolismo , Análisis de la Célula Individual , Redes Reguladoras de Genes , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Técnicas de Cocultivo , Perfilación de la Expresión Génica , Ratones Noqueados

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Type 2 diabetes mellitus (T2DM) is a complex chronic disease characterized by decreased insulin secretion and the development of insulin resistance. Previous genome-wide association studies demonstrated that single-nucleotide polymorphisms (SNPs) present in genes coding for ion channels involved in insulin secretion increase the risk of developing this disease. We determined the association of 16 SNPs found in CACNA1D, KCNQ1, KCNJ11, and CACNA1E genes and the increased probability of developing T2DM. In this work, we performed a case-control study in 301 Mexican adults, including 201 cases with diabetes and 100 controls without diabetes. Our findings indicate a moderate association between T2DM and the C allele, and the C/C genotype of rs312480 within CACNA1D. The CAG haplotype surprisingly showed a protective effect, whereas the CAC and CGG haplotypes have a strong association with T2DM. The C allele and C/C genotype of rs5219 were significantly associated with diabetes. Also, an association was observed between diabetes and the A allele and the A/A genotype of rs3753737 and rs175338 in CACNA1E. The TGG and CGA haplotypes were also found to be significantly associated. The findings of this study indicate that the SNPs examined could serve as a potential diagnostic tool and contribute to the susceptibility of the Mexican population to this disease.

Asunto(s)

Canales de Calcio Tipo L , Diabetes Mellitus Tipo 2 , Predisposición Genética a la Enfermedad , Canal de Potasio KCNQ1 , Polimorfismo de Nucleótido Simple , Canales de Potasio de Rectificación Interna , Humanos , Diabetes Mellitus Tipo 2/genética , Canales de Calcio Tipo L/genética , Canal de Potasio KCNQ1/genética , Femenino , Masculino , Canales de Potasio de Rectificación Interna/genética , Persona de Mediana Edad , Estudios de Casos y Controles , Adulto , Haplotipos , Canales de Calcio Tipo R/genética , Alelos , México , Anciano , Estudios de Asociación Genética , Genotipo , Frecuencia de los Genes , Proteínas de Transporte de Catión

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Despite the efforts made to promote consumption, some countries are not increasing their fruit and vegetable intake, while household structures are undergoing relevant changes. Fruit and vegetable consumption is necessary but not sufficient for a healthy diet. Previous research has linked adequate fruit and vegetable consumption to a lower risk of cardiovascular diseases, type 2 diabetes, and some mental health conditions. Furthermore, millions of deaths are reported annually worldwide due to diets low in fruit and vegetables, highlighting their critical public health importance. This study aims to separately analyze the purchases of fruit and vegetables in single-person households. We used three waves of the Family Budget Survey, Encuesta de Presupuestos Familiares, in Chile, which is nationally representative of urban areas and includes over 10,000 households in each wave. We employed descriptive statistics to examine the characteristics of the head of household and the food shopper as well as the structure, composition, and overall characteristics of households. Additionally, we performed separate analyses for fruit and vegetable purchases, using these variables to determine the marginal effect on the probability of purchasing fruit or vegetables through probit models. Results show that, from 2011-2012 to 2021-2022, the share of households not purchasing fruit and vegetables increased from 5.0% to 8.4% and that, in single-person households, it rose from 11.2% to 19.1%. Male-headed, single-person households with low education and income were more likely not to purchase fruit, and these households also have decreasing vegetable purchases. Additionally, household income significantly impacts fruit purchases but does not significantly affect vegetable purchases. Our findings highlight the importance of considering single-person households as a target population segment for future public policies to promote fruit and vegetable consumption.

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Composición Familiar , Frutas , Verduras , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Chile , Persona Soltera/estadística & datos numéricos , Comportamiento del Consumidor/estadística & datos numéricos , Adulto Joven , Anciano , Encuestas y Cuestionarios , Dieta/estadística & datos numéricos , Adolescente

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Metropolitan Mexico City (MMC) children and young adults exhibit overlapping Alzheimer and Parkinsons' diseases (AD, PD) and TAR DNA-binding protein 43 pathology with magnetic ultrafine particulate matter (UFPM) and industrial nanoparticles (NPs). We studied magnetophoresis, electron microscopy and energy-dispersive X-ray spectrometry in 203 brain samples from 14 children, 27 adults, and 27 ALS cases/controls. Saturation isothermal remanent magnetization (SIRM), capturing magnetically unstable FeNPs ~ 20nm, was higher in caudate, thalamus, hippocampus, putamen, and motor regions with subcortical vs. cortical higher SIRM in MMC ≤ 40y. Motion behavior was associated with magnetic exposures 25-100 mT and children exhibited IRM saturated curves at 50-300 mT associated to change in NPs position and/or orientation in situ. Targeted magnetic profiles moving under AC/AD magnetic fields could distinguish ALS vs. controls. Motor neuron magnetic NPs accumulation potentially interferes with action potentials, ion channels, nuclear pores and enhances the membrane insertion process when coated with lipopolysaccharides. TEM and EDX showed 7-20 nm NP Fe, Ti, Co, Ni, V, Hg, W, Al, Zn, Ag, Si, S, Br, Ce, La, and Pr in abnormal neural and vascular organelles. Brain accumulation of magnetic unstable particles start in childhood and cytotoxic, hyperthermia, free radical formation, and NPs motion associated to 30-50 µT (DC magnetic fields) are critical given ubiquitous electric and magnetic fields exposures could induce motion behavior and neural damage. Magnetic UFPM/NPs are a fatal brain cargo in children's brains, and a preventable AD, PD, FTLD, ALS environmental threat. Billions of people are at risk. We are clearly poisoning ourselves.

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BACKGROUND: Douglas-fir (Pseudotsuga menziesii [Mirb.] Franco) plays a critical role in the ecology and economy of Western North America. This conifer species comprises two distinct varieties: the coastal variety (var. menziesii) along the Pacific coast, and the interior variety (var. glauca) spanning the Rocky Mountains into Mexico, with instances of inter-varietal hybridization in Washington and British Columbia. Recent investigations have focused on assessing environmental pressures shaping Douglas-fir's genomic variation for a better understanding of its evolutionary and adaptive responses. Here, we characterize range-wide population structure, estimate inter-varietal hybridization levels, identify candidate loci for climate adaptation, and forecast shifts in species and variety distribution under future climates. RESULTS: Using a custom SNP-array, we genotyped 540 trees revealing four distinct clusters with asymmetric admixture patterns in the hybridization zone. Higher genetic diversity observed in coastal and hybrid populations contrasts with lower diversity in inland populations of the southern Rockies and Mexico, exhibiting a significant isolation by distance pattern, with less marked but still significant isolation by environment. For both varieties, we identified candidate loci associated with local adaptation, with hundreds of genes linked to processes such as stimulus response, reactions to chemical compounds, and metabolic functions. Ecological niche modeling revealed contrasting potential distribution shifts among the varieties in the coming decades, with interior populations projected to lose habitat and become more vulnerable, while coastal populations are expected to gain suitable areas. CONCLUSIONS: Overall, our findings provide crucial insights into the population structure and adaptive potential of Douglas-fir, with the coastal variety being the most likely to preserve its evolutionary path throughout the present century, which carry implications for the conservation and management of this species across their range.

Asunto(s)

Pseudotsuga , Pseudotsuga/genética , Adaptación Fisiológica/genética , Variación Genética/genética , Hibridación Genética , Selección Genética , México , Polimorfismo de Nucleótido Simple , Colombia Británica

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BACKGROUND: Infertility is a growing global health concern affecting millions of couples worldwide. Among several factors, an extreme body weight adversely affects reproductive functions. Leptin is a well-known adipokine that serves as an endocrine signal between adiposity and fertility. However, the exact mechanisms underlying the effects of high leptin level on female reproduction remain unclear. METHODS: Transgenic pigs overexpressing leptin (♀) were produced by backcrossing and screened for leptin overexpression. The growth curve, fat deposition, reproductive performance, apoptosis, serum hormones and cholesterol production, RNA sequencing, and single-nucleus RNA sequencing (snRNA-seq) of the leptin-overexpressing pigs and wild-type group were evaluated. RESULTS: Transgenic pigs overexpressing leptin (♀) were obtained, which exhibited significantly reduced body weight, body size, and back fat thickness. These pigs manifested a late onset of puberty (330 ± 54.3 vs. 155 ± 14.7 days), irregular estrous behavior characterized by increased inter-estrous interval (29.2 ± 0 vs. 21.3 ± 0.7 days), and more number of matings until pregnancy (at least 3 times). This reproductive impairment in leptin pigs was related to hormonal imbalances characterized by increased levels of FSH, LH, prolactin, E2, P4, and TSH, altered steroidogenesis such as increased levels of serum cholesterol esters along with steroidogenic markers (StAR, CYP19A), and ovarian dysfunctions manifested by neutrophilic infiltration and low expression of caspase-3 positive cells in the ovaries. Moreover, bulk RNA sequencing of the ovaries also revealed neutrophilic infiltration followed by upregulation of inflammation-related genes. Furthermore, snRNA-seq reflected that leptin overexpression triggered immune response, suppressed follicle development and luteinization, resulting in metabolic dysfunction and hormone imbalance in the ovary. CONCLUSIONS: Low body weight in leptin overexpressing pigs adversely affects the reproductive performance, causing delayed puberty, irregular estrous cycles, and reduced breeding efficiency. This is linked to metabolic imbalances, an increased immune response, and altered ovarian functions. This study provides a theoretical basis for the complex mechanisms underlying leptin, and infertility by employing leptin-overexpressing female pigs.

Asunto(s)

Animales Modificados Genéticamente , Leptina , Reproducción , Animales , Femenino , Leptina/sangre , Porcinos , Reproducción/fisiología , Modelos Animales de Enfermedad

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The methylenetetrahydrofolate reductase (MTHFR) gene 677C➔T polymorphism is capable of altering folate metabolism and can modify certain neoplasia risk. Reports have suggested that folate can have an influence on bone development and so it is of interest to know if the MTHFR 677C➔T polymorphism is associated with the malignant transformation process of this tissue. The polymorphism was determined in 55 patients with osteosarcoma and in 180 healthy individuals. Compared with C/T+C/C genotypes, a 3.7-fold reduction in osteosarcoma probability is possible with the T/T genotype (OR 0.27, CI 95% 0.07-0.82). Undoubtedly, further studies, utilizing large samples and carried out on different populations, are necessary to confirm these results.

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This work aims at proposing an affordable, non-wearable system to detect falls of people in need of care. The proposal uses artificial vision based on deep learning techniques implemented on a Raspberry Pi4 4GB RAM with a High-Definition IR-CUT camera. The CNN architecture classifies detected people into five classes: fallen, crouching, sitting, standing, and lying down. When a fall is detected, the system sends an alert notification to mobile devices through the Telegram instant messaging platform. The system was evaluated considering real daily indoor activities under different conditions: outfit, lightning, and distance from camera. Results show a good trade-off between performance and cost of the system. Obtained performance metrics are: precision of 96.4%, specificity of 96.6%, accuracy of 94.8%, and sensitivity of 93.1%. Regarding privacy concerns, even though this system uses a camera, the video is not recorded or monitored by anyone, and pictures are only sent in case of fall detection. This work can contribute to reducing the fatal consequences of falls in people in need of care by providing them with prompt attention. Such a low-cost solution would be desirable, particularly in developing countries with limited or no medical alert systems and few resources.

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Accidentes por Caídas , Humanos , Accidentes por Caídas/prevención & control , Aprendizaje Profundo , Computadores , Algoritmos

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Molecular and cellular characterization of tumors is essential due to the complex and heterogeneous nature of cancer. In recent decades, many bioinformatic tools and experimental techniques have been developed to achieve personalized characterization of tumors. However, sample handling continues to be a major challenge as limitations such as prior treatments before sample acquisition, the amount of tissue obtained, transportation, or the inability to process fresh samples pose a hurdle for experimental strategies that require viable cell suspensions. Here, we present an optimized protocol that allows the recovery of highly viable cell suspensions from breast cancer primary tumor biopsies. Using these cell suspensions we have successfully characterized genome architecture through Hi-C. Also, we have evaluated single-cell gene expression and the tumor cellular microenvironment through single-cell RNAseq. Both technologies are key in the detailed and personalized molecular characterization of tumor samples. The protocol described here is a cost-effective alternative to obtain viable cell suspensions from biopsies simply and efficiently.