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Recent decades have witnessed substantial changes in freshwater biodiversity worldwide. Although research has shown that freshwater biodiversity can be shaped by changes in habitat diversity and human-induced pressure, the potentials for interaction between these drivers and freshwater biodiversity at large spatial extents remain unclear. To address these issues, we employed a spatially extensive multitrophic fish and insect database from 3323 stream sites across the United States, to investigate the ability of habitat diversity to modulate the effect of human pressure on the richness and abundance of fish and insects. We found evidence that high levels of habitat diversity were associated with increased richness and abundance of fish and insects (including whole-assemblage and individual trophic guilds). We also show that the effects of human pressure on the richness and abundance of fish and insects tend to become positive at high levels of habitat diversity. Where habitat diversity is low, human pressure strongly reduces insect richness and abundance, whereas these reductions are attenuated at high levels of habitat diversity. Structural equation modeling revealed that human pressure reduced habitat diversity, indirectly negatively affecting the richness and abundance of fish and insects. These findings illustrate that, in addition to promoting greater fish and insect biodiversity, habitat diversity may mitigate the deleterious effects of human pressures on these two stream assemblages. Overall, our study suggests that maintaining high levels of habitat diversity is a useful way to protect freshwater biodiversity from ongoing increases in human pressure. However, if human pressures continue to increase, this will reduce habitat diversity, further threatening stream assemblages.
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Biodiversidad , Ecosistema , Peces , Insectos , Ríos , Animales , Insectos/fisiología , Peces/fisiología , Estados Unidos , Humanos , Actividades HumanasRESUMEN
The golden mussel (Limnoperna fortunei) is an invasive bivalve that has established itself in several South American river systems, impacting ecosystem functioning. Reservoir cascades provide their larvae with the means of rapid dispersal, but the relationship between environmental variables and larval stage structure remains unclear. In this study, the density of three L. fortunei larval stages and quantitative detection using DNA are analyzed in a cascade of five reservoirs in the upper Uruguay River Basin and associated with spatiotemporal variation in environmental parameters. The analysis of L. fortunei eDNA presence and absence in freshwater systems appears to be a valuable mapping tool; however, no significant link was found between the eDNA magnitude and the overall larval density. The increase in larval density was related to the fluctuation of environmental parameters over a year, with the highest average larval densities observed in the CN and ITA reservoirs, though no significant difference was observed between the five reservoirs, where D-shaped larvae predominated. During winter, larval density decreased significantly, however, other variables also contribute to species activity and development in the upper Uruguay River Basin reservoirs and may be considered limiting factors. The relationships between environmental parameters were evaluated using a multivariate model. The interaction between reservoir area and precipitation, water temperature, electrical conductivity, and dissolved oxygen had a significant effect on larval density but showed specific influences on each larval stage. Any increase in density was regulated by dissolved oxygen and electrical conductivity content at all larval stages. Furthermore, total phosphorus affected the density of F1 and F3 larvae. The interaction between reservoir area and precipitation, nitrate content, phosphate concentrations, and water temperature had the most influence on the density of F2 and F3 larval stages; the F1 stage was mainly affected by calcium concentrations. The isolated effect of precipitation also contributed to the density of F2 and F3 larvae. Our findings shed light on the interaction between different phases of golden mussel larvae and the main nutrients found in reservoirs, which may be a determining factor in the rise in density of the non-native species in these systems.
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Monitoreo del Ambiente , Larva , Ríos , Animales , Larva/crecimiento & desarrollo , Ríos/química , Mytilidae/crecimiento & desarrollo , Uruguay , Ecosistema , Análisis Espacio-Temporal , Estaciones del Año , Contaminantes Químicos del Agua/análisis , Especies IntroducidasRESUMEN
It has been spotlighted that the Tumor Microenvironment (TME) is crucial for comprehending cancer progression and therapeutic resistance. Therefore, this comprehensive review elucidates the intricate architecture of the TME, which encompasses tumor cells, immune components, support cells, and a myriad of bioactive molecules. These constituents collectively foster dynamic interactions that underpin tumor growth, metastasis, and nuanced responses to anticancer therapies. Notably, the TME's role extends beyond mere physical support, serving as a critical mediator in cancer-cell evolution, immune modulation, and treatment outcomes. Innovations targeting the TME, including strategies focused on the vasculature, immune checkpoints, and T-cell therapies, have forged new pathways for clinical intervention. However, the heterogeneity and complexity of the TME present significant challenges, necessitating deeper exploration of its components and their interplay to enhance therapeutic efficacy. This review underscores the imperative for integrated research strategies that amalgamate insights from tumor biology, immunology, and systems biology. Such an approach aims to refine cancer treatments and improve patient prognoses by exploiting the TME's complexity.
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BACKGROUND: This study investigates the mutational profile of the KIT gene in primary and metastatic melanomas, highlighting the significance of genetic heterogeneity. METHODS: This research is a retrospective cohort that includes formalin-fixed and paraffin-embedded melanoma samples obtained from Hospital São Paulo, Brazil, between the years of 1996 and 2010. The research encompasses primary melanomas of the superficial spreading (SSM) and acral lentiginous (AL) subtypes and their metastases, using next-generation sequencing to explore genetic heterogeneity. RESULTS: Despite losing 57 samples due to quality issues, 27 samples from 20 patients were analyzed, revealing a nearly equal distribution between AL and SSM subtypes. Both histological subtypes revealed KIT gene variants, including previously undescribed variants and polymorphisms, emphasizing the role of such mutations in melanoma pathogenesis and the potential for targeted therapies. Tumor heterogeneity was also observed in both histological subtypes. CONCLUSIONS: The study underscores the complexity of melanoma, driven by diverse mutational landscapes within and across tumors and advocates for personalized treatment approaches based on detailed molecular profiling. Despite limitations like sample size, this research lays the groundwork for further investigation into melanoma's genetic intricacies and therapeutic vulnerabilities.
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Introduction: Understanding the relationships between taxonomic, functional, and phylogenetic diversity and endemism across environmental gradients is essential for elucidating the eco-evolutionary mechanisms that shape local plant communities. Methods: A database was compiled from field surveys, national herbarium records, and virtual records of perennial plant specimens collected in the aridity gradient of northern Chile, between 18 and 32°S. A large-scale dated phylogeny of available perennial plants was used, and 11 functional traits were selected to construct a dendrogram using the Unweighted Pair-Group Method with Arithmetic Mean (UPGMA) method for the species present in our database. We calculated spatial patterns of a-diversity, including taxonomic (TD), functional (FD), and phylogenetic (PD) diversity, as well as weighted (WE), functional (FE), and phylogenetic (PE) endemism. We used multiscale geographically weighted regression (MGWR) to identify spatial congruencies and discrepancies among these dimensions and to test different eco-evolutionary processes. Results: The diversity indices TD, FD and PD showed similar geographic patterns (R2 > 0.93), with lower diversity observed in absolute desert regions. The pattern of weighted endemism (WE) showed a weak association with functional endemism (FE) and phylogenetic endemism (PE) (local R2 < 0.48). The regions with lower FD or PD than expected given the TD (i.e. FD
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BACKGROUND: Berry quality potential from a single vineyard is mainly defined based on some physicochemical parameters and subjective assessments. In this way, berry maturity variability would be a key factor affecting berry quality. METHODS: This trial aimed to study the effects of the maturity variability of berries harvested from plots of low (~37,080 kg ha-1), middle (~12,545 kg ha-1), and high (~1476 kg ha-1) quality potential on berry and wine physicochemical parameters of Cabernet Sauvignon in two consecutive seasons. The quality potential of the plots was defined by the winemakers considering mostly yield per hectare and the final price of their wines. RESULTS: The berry heterogeneous maturity of soluble solids and berry weight in Cabernet Sauvignon was confirmed. The coefficient of variability (CV) of berry weight of high-quality plots was high at véraison and decreased as ripening progressed, reaching CV of 19.9% at harvest. Low-quality plots showed the lowest CV of berry weight in all the studied dates, whereas high-quality plots presented the lowest CV in soluble solids content of berries, reaching a 5.1% of variability at harvest. The physicochemical parameters showed that high-quality plots were characterized by high levels of soluble solids and phenolic maturity parameters, whereas samples from low-quality plots reached high berry weight and malic acid content. Berry differences among the physicochemical parameters determined wine quality, which allowed for plots to be classified by their potential quality at harvest. CONCLUSIONS: Studying maturity variability of soluble solids and berry weight will allow for sampling to be sectorized within a vineyard to reduce the extremes of maturity that would affect wine quality and productive goals of winemakers.
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Relaxing the molecular clock using models of how substitution rates change across lineages has become essential for addressing evolutionary problems. The diversity of rate evolution models and their implementations are substantial, and studies have demonstrated their impact on divergence time estimates can be as significant as that of calibration information. In this review, we trace the development of rate evolution models from the proposal of the molecular clock concept to the development of sophisticated Bayesian and non-Bayesian methods that handle rate variation in phylogenies. We discuss the various approaches to modeling rate evolution, provide a comprehensive list of available software, and examine the challenges and advancements of the prevalent Bayesian framework, contrasting them to faster non-Bayesian methods. Lastly, we offer insights into potential advancements in the field in the era of big data.
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Teorema de Bayes , Evolución Molecular , Modelos Genéticos , Filogenia , Programas InformáticosRESUMEN
This study aimed to assess the impact of adaptation of ten strains of O157:H7 and non-O157 Escherichia coli to low pH (acid shock or slow acidification) and the effects of this exposure or not on the resistance of E. coli strains to UV radiation in orange juice (pH 3.5). The acid-shocked cells were obtained through culture in tryptic soy broth (TSB) with a final pH of 4.8, which was adjusted by hydrochloric, lactic, or citric acid and subsequently inoculated in orange juice at 4 °C for 30 days. No significant differences (p > 0.05) in survival in orange juice were observed between the serotypes O157:H7 and non-O157:H7 for acid-shocked experiments. After slow acidification, where the cells were cultured in TSB supplemented with glucose 1% (TSB + G), a significant increase (p < 0.05) in survival was observed for all strains evaluated. The D-values (radiation dose (J/cm2) necessary to decrease the microbial population by 90%) were determined as the inverse of the slopes of the regressions (k) obtained by plotting log (N/N0). The results show that among the strains tested, E. coli O157:H7 (303/00) and O26:H11 were the most resistant and sensitive strains, respectively. According to our results, the method of acid adaptation contributes to increasing the UV resistance for most of the strains tested.
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Adaptación Fisiológica , Citrus sinensis , Escherichia coli O157 , Jugos de Frutas y Vegetales , Rayos Ultravioleta , Escherichia coli O157/efectos de la radiación , Escherichia coli O157/crecimiento & desarrollo , Escherichia coli O157/efectos de los fármacos , Jugos de Frutas y Vegetales/microbiología , Jugos de Frutas y Vegetales/análisis , Citrus sinensis/microbiología , Citrus sinensis/química , Concentración de Iones de Hidrógeno , Escherichia coli/efectos de la radiación , Escherichia coli/efectos de los fármacos , Ácidos/farmacología , Recuento de Colonia Microbiana , Microbiología de Alimentos , Viabilidad Microbiana/efectos de la radiación , Viabilidad Microbiana/efectos de los fármacos , Irradiación de AlimentosRESUMEN
The existing literature provides limited insights into the dynamics of phytoplankton communities and the spatial heterogeneity of physicochemical parameters in multisystem cascade reservoirs (interconnected reservoirs derived from different rivers). The existing studies are concentrated on cascade reservoirs (interconnected reservoirs derived from the same river). To address this knowledge gap, the aims of the present study were as follows: (1) investigate the spatial heterogeneity, within and between reservoirs, of geochemical parameters associated with the eutrophication process, considering total phosphorus, chlorophyll-a, pheophytin, and metals (chromium, copper, nickel, lead, zinc, iron, and manganese); (2) evaluate sediment quality at the designated locations; (3) assess differences in the richness and concentration of sedimentary photopigments between the reservoirs. Application of principal component analysis revealed discernible gradients for the abiotic variables, although the differences were not statistically significant (one-way PERMANOVA test, p > 0.05). The observations suggested a tendency towards spatial homogeneity within and between the reservoirs. The metal concentrations were consistent with regional reference values, while phosphorus levels in the sediment approached the threshold for classification as pollution (~ 2000 mg/kg). Analysis of pigments indicated low dissimilarity among the reservoirs, which could be mainly attributed to the eutrophication process and high connectivity of the sampled areas. To counteract ongoing biotic homogenization, it is essential to reduce nutrient inputs and invest in ecological protection and restoration programs. The analysis of sedimentary photopigments provides an efficient and cost-effective alternative way to assess phytoplankton communities.
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Monitoreo del Ambiente , Eutrofización , Sedimentos Geológicos , Sedimentos Geológicos/química , Fitoplancton , Clorofila A , Ríos/química , Fósforo/análisis , Contaminantes Químicos del Agua/análisis , Clorofila/análisisRESUMEN
Chromosomal instability (CIN), characterized by fluctuations in chromosome number or structure within cells, stands out as a hallmark of cancer, enabling tumors to thrive in hostile conditions. CIN serves as a driver of genetic diversity, giving rise to clonal heterogeneity (CH). Emerging evidence points to a potential correlation between CIN, CH, and the prognosis of breast cancer (BC) patients, especially in tumors exhibiting overexpression of the human epidermal growth factor receptor 2 (HER2+). However, our understanding of the role of CIN in other subtypes of BC is limited. Furthermore, it remains unclear whether CIN levels above a certain threshold in BC tumors could adversely affect tumor growth, or if lower to moderate levels of CIN might be associated with a more favorable prognosis for BC patients compared to elevated levels. Elucidating these relationships could significantly influence risk assessment and the formulation of future therapeutic approaches targeting CIN in BC. This study aimed to assess CIN and CH in tumor tissue samples obtained from Colombian patients diagnosed with luminal A, luminal B, HER2+, or triple-negative BC, and compare them with established clinicopathological parameters. The findings of this study indicate that BC patients exhibit intermediate CIN, high CH, and stable aneuploidy. All these characteristics were found to be related to clinicopathological features. Our results suggest that the identification of CIN, CH, and aneuploidy could improve cancer risk stratification, which could help to clarify the prediction of clinical outcomes and guide personalized therapeutic strategies for patients with different BC subtypes.
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Neoplasias de la Mama , Inestabilidad Cromosómica , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Persona de Mediana Edad , Adulto , Anciano , Heterogeneidad Genética , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , PronósticoRESUMEN
BACKGROUND: The Gran Chaco ecoregion is a well-known hotspot of several neglected tropical diseases (NTDs) including Chagas disease, soil-transmitted helminthiasis and multiparasitic infections. Interspecific interactions between parasite species can modify host susceptibility, pathogenesis and transmissibility through immunomodulation. Our objective was to test the association between human co-infection with intestinal parasites and host parasitaemia, infectiousness to the vector and immunological profiles in Trypanosoma cruzi-seropositive individuals residing in an endemic region of the Argentine Chaco. METHODS: We conducted a cross-sectional serological survey for T. cruzi infection along with an intestinal parasite survey in two adjacent rural villages. Each participant was tested for T. cruzi and Strongyloides stercoralis infection by serodiagnosis, and by coprological tests for intestinal parasite detection. Trypanosoma cruzi bloodstream parasite load was determined by quantitative PCR (qPCR), host infectiousness by artificial xenodiagnosis and serum human cytokine levels by flow cytometry. RESULTS: The seroprevalence for T. cruzi was 16.1% and for S. stercoralis 11.5% (n = 87). We found 25.3% of patients with Enterobius vermicularis. The most frequent protozoan parasites were Blastocystis spp. (39.1%), Giardia lamblia (6.9%) and Cryptosporidium spp. (3.4%). Multiparasitism occurred in 36.8% of the examined patients. Co-infection ranged from 6.9% to 8.1% for T. cruzi-seropositive humans simultaneously infected with at least one protozoan or helminth species, respectively. The relative odds of being positive by qPCR or xenodiagnosis (i.e. infectious) of 28 T. cruzi-seropositive patients was eight times higher in people co-infected with at least one helminth species than in patients with no such co-infection. Trypanosoma cruzi parasite load and host infectiousness were positively associated with helminth co-infection in a multiple regression analysis. Interferon-gamma (IFN-γ) response, measured in relation to interleukin (IL)-4 among humans infected with T. cruzi only, was 1.5-fold higher than for T. cruzi-seropositive patients co-infected with helminths. The median concentration of IL-4 was significantly higher in T. cruzi-seropositive patients with a positive qPCR test than in qPCR-negative patients. CONCLUSIONS: Our results show a high level of multiparasitism and suggest that co-infection with intestinal helminths increased T. cruzi parasitaemia and upregulated the Th2-type response in the study patients.
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Enfermedad de Chagas , Coinfección , Helmintiasis , Parasitosis Intestinales , Trypanosoma cruzi , Humanos , Trypanosoma cruzi/inmunología , Trypanosoma cruzi/genética , Trypanosoma cruzi/aislamiento & purificación , Coinfección/parasitología , Coinfección/epidemiología , Coinfección/inmunología , Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/complicaciones , Enfermedad de Chagas/parasitología , Enfermedad de Chagas/sangre , Enfermedad de Chagas/inmunología , Animales , Adulto , Estudios Transversales , Masculino , Femenino , Parasitosis Intestinales/epidemiología , Parasitosis Intestinales/parasitología , Parasitosis Intestinales/complicaciones , Parasitosis Intestinales/inmunología , Persona de Mediana Edad , Helmintiasis/complicaciones , Helmintiasis/parasitología , Helmintiasis/epidemiología , Helmintiasis/inmunología , Adulto Joven , Adolescente , Argentina/epidemiología , Estudios Seroepidemiológicos , Strongyloides stercoralis/inmunología , Strongyloides stercoralis/aislamiento & purificación , Parasitemia/parasitología , Parasitemia/epidemiología , Células Th2/inmunología , Niño , Estrongiloidiasis/epidemiología , Estrongiloidiasis/parasitología , Estrongiloidiasis/complicaciones , Estrongiloidiasis/inmunología , Estrongiloidiasis/sangre , Anciano , Citocinas/sangre , Anticuerpos Antiprotozoarios/sangreRESUMEN
Leukemia is associated with exposure to radiation, benzene derivatives, and pesticides. Previous research has documented an increase in work-related leukemia in the Latin American Andean region. To date, there are only few studies in Ecuador on the impact of oil exploitation on adjacent indigenous communities. Our study aims to show the impact of leukemia on the working-age population. For the calculation of morbidity and mortality rates, we used hospital discharge and death records from the National Institute of Statistics of Ecuador. These data were collected and adjusted to the corresponding province's population for further analysis. Large differences were observed between provinces in adjusted rates of leukemia mortality and morbidity in the working-age population. The variations in altitude among different areas in Ecuador give the provinces a distinct geographic identity. Likewise, the provinces with the highest morbidity and mortality rankings, such as Azuay, Loja, Imbabura, and Tungurahua, have an average altitude above 2000 meters. As a result, there are variations in the average temperature, exposure to solar and cosmic radiation, and mining and farming methods. The observed differences warrant the future collection of geolocation data for affected individuals. This could help to better understand how leukemia cases have demogrpahic hotspots in the country, identify possible risk factors associated with the disease in each region, and design more effective prevention and control strategies.
La leucemia es una enfermedad a consecuencia, además de factores genéticos, de la exposición a radiaciones, derivados del benceno y pesticidas. Investigaciones anteriores han documentado un aumento de la leucemia ocupacional en la región andina de América Latina. Hasta la fecha, existen sólo unos pocos estudios en Ecuador sobre el impacto de la explotación petrolera en las comunidades indígenas. Nuestro objetivo es mostrar el impacto de la leucemia en la población en edad de trabajar. Para el cálculo de las tasas de morbimortalidad se utilizaron los registros de altas hospitalarias y defunciones del Instituto Nacional de Estadística del Ecuador. Estos datos fueron recopilados y estimadas las tasas ajustadas. Se observaron grandes diferencias entre provincias en las tasas ajustadas de mortalidad y morbilidad por leucemia en la población en edad de trabajar. Asimismo, las provincias con mayor ranking de morbilidad y mortalidad, como Azuay, Loja, Imbabura y Tungurahua, coinciden en tener una altitud promedio superior a los 2000 metros. Hay provincias de baja altitud en la costa y provincias por encima de los 2000 metros en la sierra, lo que le da a las provincias del Ecuador una identidad geográfica distintiva. Como resultado, existen variaciones en la temperatura promedio, la exposición a la radiación solar y cósmica, y actividades de minería y agricultura. Las diferencias observadas, recomiendan la recopilación futura de datos de geolocalización de las personas afectadas. Esto podría ayudarnos a comprender mejor cómo se distribuyen los casos de leucemia, identificar posibles factores de riesgo asociados a la enfermedad en cada región y diseñar estrategias de prevención y control más efectivas.
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BACKGROUND: The emergence of pyrethroid resistance has threatened the elimination of Triatoma infestans from the Gran Chaco ecoregion. We investigated the status and spatial distribution of house infestation with T. infestans and its main determinants in Castelli, a municipality of the Argentine Chaco with record levels of triatomine pyrethroid resistance, persistent infestation over 2005-2014, and limited or no control actions over 2015-2020. METHODS: We conducted a 2-year longitudinal survey to assess triatomine infestation by timed manual searches in a well-defined rural section of Castelli including 14 villages and 234 inhabited houses in 2018 (baseline) and 2020, collected housing and sociodemographic data by on-site inspection and a tailored questionnaire, and synthetized these data into three indices generated by multiple correspondence analysis. RESULTS: The overall prevalence of house infestation in 2018 (33.8%) and 2020 (31.6%) virtually matched the historical estimates for the period 2005-2014 (33.7%) under recurrent pyrethroid sprays. While mean peridomestic infestation remained the same (26.4-26.7%) between 2018 and 2020, domestic infestation slightly decreased from 12.2 to 8.3%. Key triatomine habitats were storerooms, domiciles, kitchens, and structures occupied by chickens. Local spatial analysis showed significant aggregation of infestation and bug abundance in five villages, four of which had very high pyrethroid resistance approximately over 2010-2013, suggesting persistent infestations over space-time. House bug abundance within the hotspots consistently exceeded the estimates recorded in other villages. Multiple regression analysis revealed that the presence and relative abundance of T. infestans in domiciles were strongly and negatively associated with indices for household preventive practices (pesticide use) and housing quality. Questionnaire-derived information showed extensive use of pyrethroids associated with livestock raising and concomitant spillover treatment of dogs and (peri) domestic premises. CONCLUSIONS: Triatoma infestans populations in an area with high pyrethroid resistance showed slow recovery and propagation rates despite limited or marginal control actions over a 5-year period. Consistent with these patterns, independent experiments confirmed the lower fitness of pyrethroid-resistant triatomines in Castelli compared with susceptible conspecifics. Targeting hotspots and pyrethroid-resistant foci with appropriate house modification measures and judicious application of alternative insecticides with adequate toxicity profiles are needed to suppress resistant triatomine populations and prevent their eventual regional spread.
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Enfermedad de Chagas , Resistencia a los Insecticidas , Insecticidas , Piretrinas , Triatoma , Animales , Triatoma/efectos de los fármacos , Triatoma/fisiología , Piretrinas/farmacología , Argentina , Insecticidas/farmacología , Enfermedad de Chagas/transmisión , Enfermedad de Chagas/epidemiología , Humanos , Estudios Longitudinales , Insectos Vectores/efectos de los fármacos , Insectos Vectores/fisiología , Vivienda , Ecosistema , Control de InsectosRESUMEN
Leukemia is associated with exposure to radiation, benzene derivatives, and pesticides. Previous research has documented an increase in work-related leukemia in the Latin American Andean region. To date, there are only few studies in Ecuador on the impact of oil exploitation on adjacent indigenous communities. Our study aims to show the impact of leukemia on the working-age population. For the calculation of morbidity and mortality rates, we used hospital discharge and death records from the National Institute of Statistics of Ecuador. These data were collected and adjusted to the corresponding province's population for further analysis. Large differences were observed between provinces in adjusted rates of leukemia mortality and morbidity in the working-age population. The variations in altitude among different areas in Ecuador give the provinces a distinct geographic identity. Likewise, the provinces with the highest morbidity and mortality rankings, such as Azuay, Loja, Imbabura, and Tungurahua, have an average altitude above 2000 meters. As a result, there are variations in the average temperature, exposure to solar and cosmic radiation, and mining and farming methods. The observed differences warrant the future collection of geolocation data for affected individuals. This could help to better understand how leukemia cases have demogrpahic hotspots in the country, identify possible risk factors associated with the disease in each region, and design more effective prevention and control strategies.
La leucemia es una enfermedad a consecuencia, además de factores genéticos, de la exposición a radiaciones, derivados del benceno y pesticidas. Investigaciones anteriores han documentado un aumento de la leucemia ocupacional en la región andina de América Latina. Hasta la fecha, existen sólo unos pocos estudios en Ecuador sobre el impacto de la explotación petrolera en las comunidades indígenas. Nuestro objetivo es mostrar el impacto de la leucemia en la población en edad de trabajar. Para el cálculo de las tasas de morbimortalidad se utilizaron los registros de altas hospitalarias y defunciones del Instituto Nacional de Estadística del Ecuador. Estos datos fueron recopilados y estimadas las tasas ajustadas. Se observaron grandes diferencias entre provincias en las tasas ajustadas de mortalidad y morbilidad por leucemia en la población en edad de trabajar. Asimismo, las provincias con mayor ranking de morbilidad y mortalidad, como Azuay, Loja, Imbabura y Tungurahua, coinciden en tener una altitud promedio superior a los 2000 metros. Hay provincias de baja altitud en la costa y provincias por encima de los 2000 metros en la sierra, lo que le da a las provincias del Ecuador una identidad geográfica distintiva. Como resultado, existen variaciones en la temperatura promedio, la exposición a la radiación solar y cósmica, y actividades de minería y agricultura. Las diferencias observadas, recomiendan la recopilación futura de datos de geolocalización de las personas afectadas. Esto podría ayudarnos a comprender mejor cómo se distribuyen los casos de leucemia, identificar posibles factores de riesgo asociados a la enfermedad en cada región y diseñar estrategias de prevención y control más efectivas.
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Leucemia , Humanos , Ecuador/epidemiología , Leucemia/epidemiología , Leucemia/mortalidad , Leucemia/etiología , Adulto , Factores de Riesgo , Persona de Mediana Edad , Masculino , Femenino , Altitud , Adulto Joven , Exposición a Riesgos Ambientales/efectos adversos , Adolescente , Exposición Profesional/efectos adversosRESUMEN
We present a methodology designed to study the spatial heterogeneity of climate change. Our approach involves decomposing the observed changes in temperature patterns into multiple trend, cycle, and seasonal components within a spatio-temporal model. We apply this method to test the hypothesis of a global long-term temperature trend against multiple trends in distinct biomes. Applying this methodology, we delve into the examination of heterogeneity of climate change in Brazil-a country characterized by a spectrum of climate zones. The findings challenge the notion of a global trend, revealing the presence of distinct trends in warming effects, and more accelerated trends for the Amazon and Cerrado biomes, indicating a composition between global warming and deforestation in determining changes in permanent temperature patterns.
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Cambio Climático , Ecosistema , Brasil , Temperatura , Estaciones del Año , Conservación de los Recursos Naturales , Calentamiento GlobalRESUMEN
Autism spectrum disorder (ASD) is a common and highly heritable neurodevelopmental disorder. During the last 15 years, advances in genomic technologies and the availability of increasingly large patient cohorts have greatly expanded our knowledge of the genetic architecture of ASD and its neurobiological mechanisms. Over two hundred risk regions and genes carrying rare de novo and transmitted high-impact variants have been identified. Additionally, common variants with small individual effect size are also important, and a number of loci are now being uncovered. At the same time, these new insights have highlighted ongoing challenges. In this perspective article, we summarize developments in ASD genetic research and address the enormous impact of large-scale genomic initiatives on ASD gene discovery.
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Trastorno del Espectro Autista , Predisposición Genética a la Enfermedad , Genómica , Humanos , Factores de Riesgo , Genómica/métodos , Trastorno del Espectro Autista/genética , Estudio de Asociación del Genoma Completo , Trastorno Autístico/genética , Trastorno Autístico/etiologíaRESUMEN
Tumor heterogeneity poses a significant challenge in osteosarcoma (OS) treatment. In this regard, the "omics" era has constantly expanded our understanding of biomarkers and altered signaling pathways (i.e., PI3K/AKT/mTOR, WNT/ß-catenin, NOTCH, SHH/GLI, among others) involved in OS pathophysiology. Despite different players and complexities, many commonalities have been described, among which the nuclear factor kappa B (NF-κB) stands out. Its altered activation is pervasive in cancer, with pleiotropic action on many disease-relevant traits. Thus, in the scope of this article, we highlight the evidence of NF-κB dysregulation in OS and its integration with other cancer-related pathways while we summarize the repertoire of compounds that have been described to interfere with its action. In silico strategies were used to demonstrate that NF-κB is closely coordinated with other commonly dysregulated signaling pathways not only by functionally interacting with several of their members but also by actively participating in the regulation of their transcription. While existing inhibitors lack selectivity or act indirectly, the therapeutic potential of targeting NF-κB is indisputable, first for its multifunctionality on most cancer hallmarks, and secondly, because, as a common downstream effector of the many dysregulated pathways influencing OS aggressiveness, it turns complex regulatory networks into a simpler picture underneath molecular heterogeneity.
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BACKGROUND: The incidence of myocardial infarction (MI) and sudden cardiac death (SCD) is significantly higher in individuals with Type 2 Diabetes Mellitus (T2DM) than in the general population. Strategies for the prevention of fatal arrhythmias are often insufficient, highlighting the need for additional non-invasive diagnostic tools. The T-wave heterogeneity (TWH) index measures variations in ventricular repolarization and has emerged as a promising predictor for severe ventricular arrhythmias. Although the EMPA-REG trial reported reduced cardiovascular mortality with empagliflozin, the underlying mechanisms remain unclear. This study investigates the potential of empagliflozin in mitigating cardiac electrical instability in patients with T2DM and coronary heart disease (CHD) by examining changes in TWH. METHODS: Participants were adult outpatients with T2DM and CHD who exhibited TWH > 80 µV at baseline. They received a 25 mg daily dose of empagliflozin and were evaluated clinically including electrocardiogram (ECG) measurements at baseline and after 4 weeks. TWH was computed from leads V4, V5, and V6 using a validated technique. The primary study outcome was a significant (p < 0.05) change in TWH following empagliflozin administration. RESULTS: An initial review of 6,000 medical records pinpointed 800 patients for TWH evaluation. Of these, 412 exhibited TWH above 80 µV, with 97 completing clinical assessments and 90 meeting the criteria for high cardiovascular risk enrollment. Empagliflozin adherence exceeded 80%, resulting in notable reductions in blood pressure without affecting heart rate. Side effects were generally mild, with 13.3% experiencing Level 1 hypoglycemia, alongside infrequent urinary and genital infections. The treatment consistently reduced mean TWH from 116 to 103 µV (p = 0.01). CONCLUSIONS: The EMPATHY-HEART trial preliminarily suggests that empagliflozin decreases heterogeneity in ventricular repolarization among patients with T2DM and CHD. This reduction in TWH may provide insight into the mechanism behind the decreased cardiovascular mortality observed in previous trials, potentially offering a therapeutic pathway to mitigate the risk of severe arrhythmias in this population. TRIAL REGISTRATION: NCT: 04117763.
Asunto(s)
Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2 , Glucósidos , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Compuestos de Bencidrilo/uso terapéutico , Compuestos de Bencidrilo/efectos adversos , Glucósidos/uso terapéutico , Glucósidos/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Anciano , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/fisiopatología , Resultado del Tratamiento , Factores de Tiempo , Potenciales de Acción/efectos de los fármacos , Arritmias Cardíacas/mortalidad , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/fisiopatología , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/diagnóstico , Electrocardiografía , Factores de RiesgoRESUMEN
There is a recent and growing interest in assessing differential responders to resistance training (RT) for diverse outcomes. Thus, the individual ability to respond to an intervention for a specific measurement, called responsiveness, remains to be better understood. Thus, the current study aimed to summarize the available information about the effects of RT on functional performance and muscle strength, power, and size in healthy adults, through the prevalence rate in different responsiveness classifications models. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was registered at the International Prospective Register of Systematic Reviews (PROSPERO, CRD42021265378). PubMed/MEDLINE, Scopus, and Embase databases were systematically searched in October 2023. A total of 13 studies were included, totaling 921 subjects. Only two studies presented a low risk of bias. Regarding the effectiveness of RT, the prevalence rate for non-responders ranged from 0% to 44% for muscle strength, from 0% to 84% for muscle size, and from 0% to 42% for functional performance, while for muscle power, the only study found showed a responsiveness rate of 37%. In conclusion, a wide range of differential responders is described for all variables investigated. However, the evidence summarized in this systematic review suggested some caution while interpreting the findings, since the body of evidence found seems to be incipient, and widely heterogeneous in methodological and statistical aspects.
RESUMEN
Glioblastoma Multiforme is a brain tumor distinguished by its aggressiveness. We suggested that this aggressiveness leads single-cell RNA-sequence data (scRNA-seq) to span a representative portion of the cancer attractors domain. This conjecture allowed us to interpret the scRNA-seq heterogeneity as reflecting a representative trajectory within the attractor's domain. We considered factors such as genomic instability to characterize the cancer dynamics through stochastic fixed points. The fixed points were derived from centroids obtained through various clustering methods to verify our method sensitivity. This methodological foundation is based upon sample and time average equivalence, assigning an interpretative value to the data cluster centroids and supporting parameters estimation. We used stochastic simulations to reproduce the dynamics, and our results showed an alignment between experimental and simulated dataset centroids. We also computed the Waddington landscape, which provided a visual framework for validating the centroids and standard deviations as characterizations of cancer attractors. Additionally, we examined the stability and transitions between attractors and revealed a potential interplay between subtypes. These transitions might be related to cancer recurrence and progression, connecting the molecular mechanisms of cancer heterogeneity with statistical properties of gene expression dynamics. Our work advances the modeling of gene expression dynamics and paves the way for personalized therapeutic interventions.