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BACKGROUND: Several dietary approaches have been used to induce remission in patients with eosinophilic esophagitis (EoE), yielding varied results. METHODS: We searched the MEDLINE, EMBASE, and Scopus databases up to May 2024 to identify studies including dietary interventions for EoE used as monotherapy. Summary estimates with 95% CIs for achieving <15 eosinophils/HPF were calculated for each approach. Fixed or random effects models were used depending on heterogeneity (I2); publication bias risks were assessed using funnel plot analyses. Subgroup analyses results were compared using meta-regression. RESULTS: Forty-three studies with 2825 patients were included in quantitative summaries. The overall rate of histologic remission was 60.6% (95% CI, 54.6-66.5%). Effectiveness rates were 94.5% (95% CI, 92.3-96.4%) for elemental diets, 63.9% (95% CI, 58.5-69.2%) for six-food elimination diets, 54.7% (95% CI, 45.7-63.6%) for four-food elimination diets, 44.3% (95% CI, 36.1-52.8%) for two-food elimination diets, 46.4% (95% CI, 40-52.9%) for one-food elimination diets, and 39.5% (95% CI, 30.3-49.2%) for allergy testing-directed food elimination diets. Overall, superior efficacy was noted in children than in adults and in retrospective compared to prospective studies. CONCLUSION: Diet therapy remains an effective therapeutic asset for pediatric and adult patients with EoE, with increasing efficacy noted as the levels of dietary restriction increase.
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Esofagite Eosinofílica , Humanos , Esofagite Eosinofílica/dietoterapia , Esofagite Eosinofílica/terapia , Criança , Adulto , Resultado do Tratamento , Feminino , Masculino , Adolescente , Pré-Escolar , DietaRESUMO
We study the ordering dynamics of nonlinear voter models with multiple states, also providing a discussion of the two-state model. The rate with which an individual adopts an opinion scales as the qth power of the number of the individual's neighbors in that state. For q>1 the dynamics favor the opinion held by the most agents. The ordering to consensus is driven by deterministic drift, and noise plays only a minor role. For q<1 the dynamics favors minority opinions, and for multistate models the ordering proceeds through a noise-driven succession of metastable states. Unlike linear multistate systems, the nonlinear model cannot be reduced to an effective two-state model. We find that the average density of active interfaces in the model with multiple opinion states does not show a single exponential decay in time for q<1, again at variance with the linear model. This highlights the special character of the conventional (linear) voter model, in which deterministic drift is absent. As part of our analysis, we develop a pair approximation for the multistate model on graphs, valid for any positive real value of q, improving on previous approximations for nonlinear two-state voter models.
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Sarcopenia is a progressive and generalized age-related skeletal muscle (SkM) disorder characterized by the accelerated loss of muscle mass (atrophy) and function. SkM atrophy is associated with increased incidence of falls, functional decline, frailty and mortality. In its early stage, SkM atrophy is associated with increased pro-inflammatory cytokine levels and proteasome-mediated protein degradation. These processes also link to the activation of atrophy associated factors and signaling pathways for which, there is a lack of approved pharmacotherapies. The objective of this study, was to characterize the capacity of the flavanol (+)-epicatechin (+Epi) to favorably modulate SkM mass and function in a rat model of aging induced sarcopenia and profile candidate mechanisms. Using 23 month old male Sprague-Dawley rats, an 8 weeks oral administration of the +Epi (1 mg per kg per day in water by gavage) was implemented while control rats only received water. SkM strength (grip), treadmill endurance, muscle mass, myofiber area, creatine kinase, lactate dehydrogenase, troponin, α-actin, tumor necrosis factor (TNF)-α and atrophy related endpoints (follistatin, myostatin, NFκB, MuRF 1, atrogin 1) were quantified in plasma and/or gastrocnemius. We also evaluated effects on insulin growth factor (IGF)-1 levels and downstream signaling (AKT/mTORC1). Treatment of aged rats with +Epi, led to significant increases in front paw grip strength, treadmill time and SkM mass vs. controls as well as beneficial changes in makers of myofiber integrity. Treatment significantly reversed adverse changes in plasma and/or SkM TNF-α, IGF-1, atrophy and protein synthesis related endpoints vs. controls. In conclusion, +Epi has the capacity to reverse sarcopenia associated detrimental changes in regulatory pathways leading to improved SkM mass and function. Given these results and its recognized safety and tolerance profile, +Epi warrants consideration for clinical trials.
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Catequina , Sarcopenia , Masculino , Ratos , Animais , Sarcopenia/metabolismo , Catequina/farmacologia , Roedores , Ratos Sprague-Dawley , Envelhecimento , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Músculo Esquelético/metabolismo , Água/metabolismoRESUMO
Pleurotus ostreatus, also known as the oyster mushroom, is a popular edible mushroom cultivated worldwide. This review aims to survey recent progress in the molecular genetics of this fungus and demonstrate its potential as a model mushroom for future research. The development of modern molecular genetic techniques and genome sequencing technologies has resulted in breakthroughs in mushroom science. With efficient transformation protocols and multiple selection markers, a powerful toolbox, including techniques such as gene knockout and genome editing, has been developed, and numerous new findings are accumulating in P. ostreatus. These include molecular mechanisms of wood component degradation, sexual development, protein secretion systems, and cell wall structure. Furthermore, these techniques enable the identification of new horizons in enzymology, biochemistry, cell biology, and material science through protein engineering, fluorescence microscopy, and molecular breeding. KEY POINTS: ⢠Various genetic techniques are available in Pleurotus ostreatus. ⢠P. ostreatus can be used as an alternative model mushroom in genetic analyses. ⢠New frontiers in mushroom science are being developed using the fungus.
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Agaricales , Pleurotus , Pleurotus/genética , Agaricales/genética , Ciência dos Materiais , Parede Celular , Embaralhamento de DNARESUMO
OBJECTIVE: Sex education is essential for an accurate approach of sexuality in adolescents, being more effective when it is carried out at early ages. This study aimed to estimate the sexual health knowledge and the information in this regard perceived by adolescents, as well as where it came from. METHODS: A cross-sectional observational study was performed in students from two public high schools in Castilla-La Mancha who were surveyed about sexual knowledge. Comparisons were made by using the Student's t test or Mann Whitney U test, the Chi-square test (or Fisher's exact test) depending on the variables. RESULTS: 248 students were included (68.1% from Madridejos and 31.9% from Herencia) with a mean age of 14.67±1.1 years. The 47.2% were women. Only 4.8% of the participants affirm to talk about sexuality with their parents. The 56% declared had consumed pornographic content, with a mean first access age of 12.8±1 years. Significant statistically differences were found between the information received in schools and in the familiar surroundings, being alcohol and drug intake, sexually transmitted infections (STI), and contraceptive methods more frequently treated at the educational centers. A 25% of the surveyed students who reported having performed sexual relations stated not having used condom. Approximately, half of the participants did not perceive a high risk of getting STIs (HIV, herpes and chlamydia) in the case of having sex without condom. CONCLUSIONS: There is a lack of sexual knowledge in adolescents, perceiving a noteworthy heterogeneity in the offered information depending on it is received in high school or in familiar surroundings.
OBJECTIVE: La educación sexual es un pilar fundamental para un correcto enfoque de la sexualidad en los adolescentes, siendo más efectiva si se realiza en edades tempranas. El objetivo de este trabajo se fundamentó en estimar los conocimientos de salud sexual y la información percibida por los adolescentes, así como de dónde provenía. METHODS: Se realizó un estudio observacional transversal en estudiantes de dos centros educativos públicos de Castilla-La Mancha a los que se les realizó una encuesta sobre conocimientos de sexualidad. Se hicieron comparaciones mediante t de student o U de Mann Whitney, o test de Chi-cuadrado (o test exacto de Fisher), según variables. RESULTS: Se incluyeron 248 encuestados/as (68,1% de Madridejos y 31,9% de Herencia) con una edad media de 14,67±1,1 años. El 47,2% fueron mujeres. Solo un 4,8% de los/as encuestados/as afirmaron hablar sobre sexualidad con sus progenitores. Un 56% afirmaron haber consumido contenido pornográfico, siendo la edad media de la primera visualización de 12,8±1 años. Se encontraron diferencias estadísticamente significativas entre la información recibida en los centros educativos y el ámbito familiar, tratándose más frecuentemente el consumo de alcohol y drogas, las infecciones de transmisión sexual (ITS) y los métodos anticonceptivos en los centros. Un cuarto de los/as encuestados/as que afirmaron haber tenido relaciones sexuales no habían utilizado preservativo. Aproximadamente, la mitad de los/as participantes no percibieron un riesgo alto de contraer ITS (VIH, herpes y clamidia) en el caso de mantener relaciones sexuales sin preservativo. CONCLUSIONS: Existe una falta de educación sexual en los/as adolescentes, percibiendo gran heterogeneidad en los conocimientos ofrecidos en los centros educativos y el ámbito familiar.
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Comportamento Sexual , Infecções Sexualmente Transmissíveis , Humanos , Adolescente , Feminino , Criança , Masculino , Estudos Transversais , Espanha , Percepção , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
Medicinal plants have been used by various cultures since pre - Hispanic times in Mexico. In this study, the use of medicinal plants in the old neighborhoods of Guadalajara, Jalisco, Mexico is described. 137 species, 130 genera and 68 families were recorded. 34% of the species belong to Asteraceae, Lamiaceae, Malvaceae and Fabaceae families. The neighborhoods of Mexicaltzingo and San Juan de Dios are the most related to the knowledge and use of medicinal plants, while El Santuario is the least similar to the rest. The diversity of uses of medicinal plants according to the Shannon index is high (between 3.0 and 4.92). The Use Value Index showed that Matricaria chamomilla L. was the species that obtained the highest valu e (0.28), followed by Gnaphalium americanum Mill. (0.23). The age group between 51 and 85 years old has greater knowledge about medicinal plants and their uses.
Las plantas medicinales han sido utilizadas por diversas culturas desde tiempos prehispánicos en México. En este estudio, se describe el uso de plantas medicinales en los barrios antiguos de Guadalajara, Jalisco, México. Se registraron 137 especies, 130 géneros y 68 familias. El 34% de las especies pertenece a las familias Asteraceae, Lamiaceae, Malvaceae y Fabaceae. Los barrios de Mexicaltzingo y San Juan de Dios son los más parecidos en cuanto al conocimiento y uso de pl antas medicinales, mientras que El Santuario es el menos afín al resto. La diversidad de usos de las plantas medicinales de acuerdo con el índice de Shannon es alta (entre 3.0 y 4.92). El Índice de Valor de Uso mostró que Matricaria chamomilla L. fue la es pecie que obtuvo el máximo valor (0.28), seguida de Gnaphalium americanum Mill. (0.23). El grupo de entre 51 - 85 de edad posee mayor conocimiento sobre las plantas medicinales y sus usos.
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Plantas Medicinais , Etnobotânica , MéxicoRESUMO
Soil fungi belonging to different functional guilds, such as saprotrophs, pathogens, and mycorrhizal symbionts, play key roles in forest ecosystems. To date, no study has compared the actual gene expression of these guilds in different forest soils. We used metatranscriptomics to study the competition for organic resources by these fungal groups in boreal, temperate, and Mediterranean forest soils. Using a dedicated mRNA annotation pipeline combined with the JGI MycoCosm database, we compared the transcripts of these three fungal guilds, targeting enzymes involved in C- and N mobilization from plant and microbial cell walls. Genes encoding enzymes involved in the degradation of plant cell walls were expressed at a higher level in saprotrophic fungi than in ectomycorrhizal and pathogenic fungi. However, ectomycorrhizal and saprotrophic fungi showed similarly high expression levels of genes encoding enzymes involved in fungal cell wall degradation. Transcripts for N-related transporters were more highly expressed in ectomycorrhizal fungi than in other groups. We showed that ectomycorrhizal and saprotrophic fungi compete for N in soil organic matter, suggesting that their interactions could decelerate C cycling. Metatranscriptomics provides a unique tool to test controversial ecological hypotheses and to better understand the underlying ecological processes involved in soil functioning and carbon stabilization.
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Florestas , Fungos , Microbiologia do Solo , Transcriptoma , Fungos/genética , Fungos/fisiologia , Transcriptoma/genética , Micorrizas/fisiologia , Micorrizas/genética , Perfilação da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Nitrogênio/metabolismo , Solo/química , Ecossistema , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
OBJECTIVES: To evaluate whether the severity of xerostomia in older polymedicated patients impacts oral health-related quality of life (OHRQoL). BACKGROUND: Medication-associated xerostomia is common in older people. Xerostomia may impair OHRQoL. MATERIALS AND METHODS: This cross-sectional study included older hypertensive patients from two health centres. We assessed the severity of xerostomia and OHRQoL using the Xerostomia Inventory (XI) tool, and the Oral Health Impact Profile-14 (OHIP-14) instrument, respectively. We measured unstimulated (UWS) and stimulated (SWS) salivary flows. Univariate and multiple linear regression analyses evaluated the associations of XI and OHIP-14 and different explanatory variables. RESULTS: Of the 218 patients enrolled, 51.8% had xerostomia, and 38.1% and 27.5% suffered from UWS and SWS hyposalivation, respectively. Patients with xerostomia, UWS, and SWS hyposalivation scored significantly higher on the XI. However, only those with xerostomia or UWS hyposalivation had significantly higher OHIP-14 scores. A moderate correlation was observed between XI and OHIP-14 scores. The multiple regression model showed that factors with the greatest impact on XI were the patient's complaint of xerostomia, UWS flow rate, age and sex. However, only the XI score was significantly associated with the OHIP-14 score. CONCLUSION: Xerostomia has a negative impact on OHRQoL in older polymedicated patients, but this impact is less than in other types of xerostomia. Longitudinal studies are needed to determine whether changes in the detected explanatory variables influence XI and OHIP scores in these patients.
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BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common concomitant condition in patients with inflammatory bowel disease (IBD). We aim to assess the magnitude of this association. METHODS: We searched MEDLINE, EMBASE and Scopus libraries for the period up to February 2023 to identify studies reporting cohorts of IBD patients in which NALFLD was evaluated. RESULTS: Eighty-nine studies were analyzed. The overall prevalence of NAFLD was 24.4% (95%CI, 19.3-29.8) in IBD, 20.2% (18.3-22.3) in Crohn's disease and 18.5% (16.4-20.8) for ulcerative colitis. Higher prevalence was found in male compared to female patients, in full papers compared to abstracts, and in cross-sectional studies compared to prospective and retrospective ones. The prevalence of NAFLD in IBD has increased in studies published from 2015 onwards: 23.2% (21.5-24.9) vs. 17.8% (13.2-22.9). Diagnostic methods for NAFLD determined prevalence figures, being highest in patients assessed by controlled attenuation parameter (38.8%; 33.1-44.7) compared to ultrasonography (28.5%; 23.1-34.2) or other methods. The overall prevalence of fibrosis was 16.7% (12.2-21.7) but varied greatly according to the measurement method. CONCLUSION: One-quarter of patients with IBD might present with NAFLD worldwide. This proportion was higher in recent studies and in those that used current diagnostic methods.
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Colite Ulcerativa , Doenças Inflamatórias Intestinais , Hepatopatia Gordurosa não Alcoólica , Feminino , Humanos , Masculino , Colite Ulcerativa/complicações , Colite Ulcerativa/epidemiologia , Estudos Transversais , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Cirrose Hepática/epidemiologia , Cirrose Hepática/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Prevalência , Estudos Prospectivos , Estudos Retrospectivos , Fatores de RiscoRESUMO
Annona muricata Linn. (Annonaceae) is a tropical plant with multiple beneficial health effects including anticancer properties. In breast cancer patients, overexpression of the HER2 oncoprotein corresponds to a poor prognosis, thus the main purpose of this study was to evaluate the cytotoxicity of ethanolic extracts from dried and fresh leaf of A. muricata on HER2+ breast cancer cells. MTT assays were performed and IC50 determined in HCC1954 (HER2+) cells, as well as in MCF7 (HER-) and peripheral blood mononuclear cells (PBMC) used as controls. Total polyphenol content evaluation and phytochemical screening were also performed. The cytotoxic effect of A. muricata extracts (125-1000 µg/mL) was dose-dependent and cell-type specific. The extracts exhibited higher cytotoxicity against HCC1954 than MCF7 cells, but weak toxicity against PBMC. This is the first report of the cytotoxic effect of A. muricata on HCC1954 cells, highlighting its potential for treating anti-estrogen-resistant breast cancers and low toxicity against PBMC.
Annona muricata Linn. (Annonaceae) es una planta tropical con múltiples efectos benéficos en la salud incluyendo propiedades antitumorales. En pacientes con cáncer de mama la sobreexpresión del oncogen HER2 corresponde a un mal pronóstico, por lo que el objetivo principal de este estudio fue evaluar la citotoxicidad de extractos etanólicos de hojas secas y frescas de A. muricata en células tumorales de mama HER2+. Se aplicaron pruebas de MTT y se determinaron IC50en células HCC1954 (HER2+); se utilizaron células MCF7 (HER-) y células mononucleares de sangre periférica (PBMC) como control. Se valoró también el contenido en polifenoles totales, y se realizó un tamizaje fitoquímico. El efecto citotóxico de los extractos de A. muricata (125-1000 µg/mL) fue dosis-dependiente y específico para cada tipo celular. Los extractos presentaron mayor actividad citotóxica contra HCC1954 en comparación con MCF7 y baja toxicidad contra PBMC. Este es el primer reporte del efecto citotóxico de A. muricata en HCC1954 y destaca su potencial terapéutico para tratamiento de cáncer de mama resistentes a antiestrógeno y baja citotoxicidad contra PBMC.
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Neoplasias da Mama/prevenção & controle , Annona/química , Antineoplásicos/uso terapêutico , Plantas Medicinais , Neoplasias da Mama/tratamento farmacológico , Citotoxinas/farmacologiaRESUMO
Cancer is pervasive across multicellular species, but what explains differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades (amphibians, sauropsids and mammals) we found that neoplasia and malignancy prevalence increases with adult weight (contrary to Peto's Paradox) and somatic mutation rate, but decreases with gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%) the black-footed penguin (<0.4%), ferrets (63%) and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer.
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Truffles are ascomycete hypogeous fungi belonging to the Tuberaceae family of the Pezizales order that grow in ectomycorrhizal symbiosis with tree roots, and they are known for their peculiar aromas and flavors. The axenic culture of truffle mycelium is problematic because it is not possible in many cases, and the growth rate is meager when it is possible. This limitation has prompted searching and characterizing new strains that can be handled in laboratory conditions for basic and applied studies. In this work, a new strain of Tuber borchii (strain SP1) was isolated and cultured, and its transcriptome was analyzed under different in vitro culture conditions. The results showed that the highest growth of T. borchii SP1 was obtained using maltose-enriched cultures made with soft-agar and in static submerged cultures made at 22 °C. We analyzed the transcriptome of this strain cultured in different media to establish a framework for future comparative studies, paying particular attention to the central metabolic pathways, principal secondary metabolite gene clusters, and the genes involved in producing volatile aromatic compounds (VOCs). The results showed a transcription signal for around 80% of the annotated genes. In contrast, most of the transcription effort was concentrated on a limited number of genes (20% of genes account for 80% of the transcription), and the transcription profile of the central metabolism genes was similar in the different conditions analyzed. The gene expression profile suggests that T. borchii uses fermentative rather than respiratory metabolism in these cultures, even in aerobic conditions. Finally, there was a reduced expression of genes belonging to secondary metabolite clusters, whereas there was a significative transcription of those involved in producing volatile aromatic compounds.
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Ascomicetos , Micorrizas , Transcriptoma , Ascomicetos/metabolismo , Micorrizas/genética , SimbioseRESUMO
Satureja macrostema is a plant that is located in various regions of Mexico and is used in a traditional way against illness. Essential oils (EOs) were obtained from leaves Satureja macrostema and the chemical composition was evaluated by gas chromatography-mass spectrometry (GC-MS). The antioxidant effect of the oil was assayed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and by Trolox Equivalent Antioxidant Capacity (TEAC). In vitro antibacterial activity against Escherichia coli and Staphylococcus aureus was determined using a broth microdilution assay and thin layer chromatography-direct bioautography (TLC-DB) to identify active antibacterial compounds. The EOs analysis showed 21 compounds, 99% terpenes, and 96% oxygenated monoterpenes, with trans-piperitone epoxide (46%), cis-piperitone epoxide (22%), and piperitenone oxide (11%) as more abundant compounds. Likewise, S. macrostema EOs showed an antioxidant activity of DPPH = 82%, with 50% free radical scavenging (IC50) = 7 mg/mL and TEAC = 0.005, an antibacterial effect against E. coli of 73% inhibition, and 81% over S. aureus at dose of 100 µL of undiluted crude oil. The TLC-DB assay showed that the most active compounds were derived from piperitone. The comparison with other studies on S. macrostema shows variability in the compounds and their abundances, which can be attributed to climatic factors and the maturity of plants with similar antioxidant and antibacterial activities.
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Lamiaceae , Óleos Voláteis , Satureja , Antioxidantes/farmacologia , Antioxidantes/química , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Satureja/química , Escherichia coli , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Lamiaceae/química , Óleos de Plantas/químicaRESUMO
Neurodegeneration with brain iron accumulation (NBIA) represents a group of neurodegenerative disorders characterized by abnormal iron accumulation in the brain. In Parkinson's Disease (PD), iron accumulation is a cardinal feature of degenerating regions in the brain and seems to be a key player in mechanisms that precipitate cell death. The aim of this study was to explore the genetic and genomic connection between NBIA and PD. We screened for known and rare pathogenic mutations in autosomal dominant and recessive genes linked to NBIA in a total of 4481 PD cases and 10,253 controls from the Accelerating Medicines Partnership Parkinsons' Disease Program and the UKBiobank. We examined whether a genetic burden of NBIA variants contributes to PD risk through single-gene, gene-set, and single-variant association analyses. In addition, we assessed publicly available expression quantitative trait loci (eQTL) data through Summary-based Mendelian Randomization and conducted transcriptomic analyses in blood of 1886 PD cases and 1285 controls. Out of 29 previously reported NBIA screened coding variants, four were associated with PD risk at a nominal p value < 0.05. No enrichment of heterozygous variants in NBIA-related genes risk was identified in PD cases versus controls. Burden analyses did not reveal a cumulative effect of rare NBIA genetic variation on PD risk. Transcriptomic analyses suggested that DCAF17 is differentially expressed in blood from PD cases and controls. Due to low mutation occurrence in the datasets and lack of replication, our analyses suggest that NBIA and PD may be separate molecular entities.
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Cancer is pervasive across multicellular species. Are there any patterns that can explain differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades (amphibians, sauropsids and mammals) we found that neoplasia and malignancy prevalence increases with adult weight and decreases with gestation time, contrary to Petoâ™s Paradox. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%) the black-footed penguin (<0.4%), ferrets (63%) and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer.
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Expansion of a single repetitive DNA sequence, termed a tandem repeat (TR), is known to cause more than 50 diseases1,2. However, repeat expansions are often not explored beyond neurological and neurodegenerative disorders. In some cancers, mutations accumulate in short tracts of TRs, a phenomenon termed microsatellite instability; however, larger repeat expansions have not been systematically analysed in cancer3-8. Here we identified TR expansions in 2,622 cancer genomes spanning 29 cancer types. In seven cancer types, we found 160 recurrent repeat expansions (rREs), most of which (155/160) were subtype specific. We found that rREs were non-uniformly distributed in the genome with enrichment near candidate cis-regulatory elements, suggesting a potential role in gene regulation. One rRE, a GAAA-repeat expansion, located near a regulatory element in the first intron of UGT2B7 was detected in 34% of renal cell carcinoma samples and was validated by long-read DNA sequencing. Moreover, in preliminary experiments, treating cells that harbour this rRE with a GAAA-targeting molecule led to a dose-dependent decrease in cell proliferation. Overall, our results suggest that rREs may be an important but unexplored source of genetic variation in human cancer, and we provide a comprehensive catalogue for further study.
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Expansão das Repetições de DNA , Genoma Humano , Neoplasias , Humanos , Sequência de Bases , Expansão das Repetições de DNA/genética , Genoma Humano/genética , Neoplasias/classificação , Neoplasias/genética , Neoplasias/patologia , Análise de Sequência de DNA , Regulação da Expressão Gênica , Elementos Reguladores de Transcrição/genética , Íntrons/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Proliferação de Células/efeitos dos fármacos , Reprodutibilidade dos TestesRESUMO
Peripheral inputs continuously shape brain function and can influence memory acquisition, but the underlying mechanisms have not been fully understood. Cannabinoid type-1 receptor (CB1R) is a well-recognized player in memory performance, and its systemic modulation significantly influences memory function. By assessing low arousal/non-emotional recognition memory in mice, we found a relevant role of peripheral CB1R in memory persistence. Indeed, the peripherally-restricted CB1R specific antagonist AM6545 showed significant mnemonic effects that were occluded in adrenalectomized mice, and after peripheral adrenergic blockade. AM6545 also transiently impaired contextual fear memory extinction. Vagus nerve chemogenetic inhibition reduced AM6545-induced mnemonic effect. Genetic CB1R deletion in dopamine ß-hydroxylase-expressing cells enhanced recognition memory persistence. These observations support a role of peripheral CB1R modulating adrenergic tone relevant for cognition. Furthermore, AM6545 acutely improved brain connectivity and enhanced extracellular hippocampal norepinephrine. In agreement, intra-hippocampal ß-adrenergic blockade prevented AM6545 mnemonic effects. Altogether, we disclose a novel CB1R-dependent peripheral mechanism with implications relevant for lengthening the duration of non-emotional memory.
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Norepinefrina , Receptor CB1 de Canabinoide , Animais , Camundongos , Adrenérgicos/farmacologia , Encéfalo , Hipocampo , Norepinefrina/farmacologia , Receptor CB1 de Canabinoide/antagonistas & inibidoresRESUMO
OBJECTIVE: The aim of this study was to evaluate the risk factors associated with xerostomia and hyposalivation in a group of hypertensive patients. SUBJECTS AND METHODS: A cross-sectional study was conducted. Hypertensive patients belonged to two healthcare centers were included. Xerostomia was assessed by asking a question and using the Xerostomia Inventory. Unstimulated salivary flow was collected. Different epidemiological variables were analyzed such as age, sex, habits, diseases, drugs, and blood pressure. RESULTS: 221 individuals were included. Xerostomia was reported in 51.13% of patients. Patients with xerostomia suffered more from osteoarthritis and diaphragmatic hernia. These patients took more anticoagulants (acenocoumarol), antiarrhythmics (amiodarone), analgesics (paracetamol) and epilepsy drugs (pregabalin) and less platelet aggregation inhibitors and angiotensin II receptor blockers (losartan). Unstimulated flow was reduced in 37.56% of patients. Patients suffering hyposalivation presented more diseases such as anxiety, infectious or parasitic diseases, hepatitis C, diaphragmatic hernia, and osteoarthritis. These patients took more repaglinide, thiazides, anti-inflammatories, anti-rheumatics, glucosamine, diazepam, and selective beta-2-adrenoreceptor agonists and less combinations of candesartan and diuretics. CONCLUSIONS: Xerostomia and hyposalivation are frequent in hypertensive patients. It is advisable to take into consideration the comorbidities and the drugs they receive, since they can increase the risk of these salivary disorders.
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Hérnia Diafragmática , Xerostomia , Humanos , Saliva , Estudos Transversais , Xerostomia/complicações , Fatores de Risco , Hérnia Diafragmática/complicaçõesRESUMO
BACKGROUND: Pregnancy complications vary based on the fetus's genetic sex, which may, in part, be modulated by the placenta. Furthermore, developmental differences early in life can have lifelong health outcomes. Yet, sex differences in gene expression within the placenta at different timepoints throughout pregnancy and comparisons to adult tissues remains poorly characterized. METHODS: Here, we collect and characterize sex differences in gene expression in term placentas (≥ 36.6 weeks; 23 male XY and 27 female XX). These are compared with sex differences in previously collected first trimester placenta samples and 42 non-reproductive adult tissues from GTEx. RESULTS: We identify 268 and 53 sex-differentially expressed genes in the uncomplicated late first trimester and term placentas, respectively. Of the 53 sex-differentially expressed genes observed in the term placentas, 31 are also sex-differentially expressed genes in the late first trimester placentas. Furthermore, sex differences in gene expression in term placentas are highly correlated with sex differences in the late first trimester placentas. We found that sex-differential gene expression in the term placenta is significantly correlated with sex differences in gene expression in 42 non-reproductive adult tissues (correlation coefficient ranged from 0.892 to 0.957), with the highest correlation in brain tissues. Sex differences in gene expression were largely driven by gene expression on the sex chromosomes. We further show that some gametologous genes (genes with functional copies on X and Y) will have different inferred sex differences if the X-linked gene expression in females is compared to the sum of the X-linked and Y-linked gene expression in males. CONCLUSIONS: We find that sex differences in gene expression are conserved in late first trimester and term placentas and that these sex differences are conserved in adult tissues. We demonstrate that there are sex differences associated with innate immune response in late first trimester placentas but there is no significant difference in gene expression of innate immune genes between sexes in healthy full-term placentas. Finally, sex differences are predominantly driven by expression from sex-linked genes.
Assuntos
Placenta , Caracteres Sexuais , Gravidez , Feminino , Masculino , Adulto , Humanos , Placenta/metabolismo , Primeiro Trimestre da Gravidez/genéticaRESUMO
We investigate the time evolution of the density of active links and of the entropy of the distribution of agents among opinions in multistate voter models with all-to-all interaction and on uncorrelated networks. Individual realizations undergo a sequence of eliminations of opinions until consensus is reached. After each elimination the population remains in a metastable state. The density of active links and the entropy in these states varies from realization to realization. Making some simple assumptions we are able to analytically calculate the average density of active links and the average entropy in each of these states. We also show that, averaged over realizations, the density of active links decays exponentially, with a timescale set by the size and geometry of the graph, but independent of the initial number of opinion states. The decay of the average entropy is exponential only at long times when there are at most two opinions left in the population. Finally, we show how metastable states comprising only a subset of opinions can be artificially engineered by introducing precisely one zealot in each of the prevailing opinions.