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OBJECTIVES: To assess factors associated with the risk of severe disease in children aged 5 years or younger with laboratory-confirmed respiratory syncytial virus (RSV) infection. STUDY DESIGN: We conducted a nationwide retrospective cohort study in Mexico. METHODS: Eligible participants included children aged 5 years or younger with laboratory-confirmed RSV infection January 1, 2023, and May 15, 2024. We collected relevant clinical and epidemiological data. Risk ratios (RR) and 95% confidence intervals (CI) were employed to identify factors associated with the risk of severe disease, characterized by clinical and radiographic evidence of bronchiolitis or pneumonia requiring hospital admission. RESULTS: Data from 2022 children were analyzed and the overall risk of severe disease was 21.0% (n = 424/2022). In multiple generalized linear regression analysis, a personal history of immunosuppression (due to any cause) showed a protective effect (RR = 0.14, 95% CI 0.05-0.42, P = 0.001) against severe RSV disease, while an increased risk was documented for each additional day elapsed between the date of symptom onset and the date of seeking healthcare RR = 1.06, 95% CI 1.02-1.10, P = 0.004). CONCLUSION: These findings provide insights into risk stratification and suggest specific directions for future research. This information informs the development of targeted intervention strategies to mitigate the impact of RSV infections in this vulnerable population.
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Summary: Background. Identifying factors influencing adherence, such as patients' beliefs about medication, is essential for effective asthma management. This study aims to assess and gain insight into the beliefs of patients with asthma regarding inhaled medication. Methods. This is a secondary analysis of the INSPIRERS studies. Patients aged ≥ 13 y.o., with persistent asthma and a prescription for inhaled controller were recruited from 60 primary and secondary care centres in Portugal from 2017 to 2020. Demographic and clinical characteristics were collected in a face-to-face visit. The Specific-Beliefs about Medicine Questionnaire was administered 1-week later by telephone interview. Mann-Whitney U and Kruskal-Wallis tests were used to explore relations between patients' beliefs and characteristics. Results. A total of 552 participants (mean 32.8 ± 17.3 y.o.; 64.5% female) were analysed. The Necessity score (Median 19 [p25-p75 16,22]) was significantly higher than the Concerns score (15 [16,22], p less than 0.001), resulting in a positive Necessity-Concern differential (Median 4 [0,7]). Acceptance (high necessity, low concerns) characterized 61% of participants, while 19% were ambivalent (high necessity, high concerns). Adolescents exhibited lower Necessity (Median 16 vs 20; p less than 0.001) and Concerns scores (Median 11 vs 15; p = 0.002) than adults. In primary care setting, patients had significantly lower Necessity (Median 18 vs 19; p = 0.027) and Concerns (Median 14 vs 15; p = 0.05) compared to the secondary care. Conclusions. A predominantly positive perception of inhaled asthma medication necessity was found, although ambivalence or indifference exists in about 1/5 of patients. Our findings highlight the importance of personalized approaches to address beliefs and optimise patient education.
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Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.
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Asma , Rinitis Alérgica , Rinitis , Humanos , Rinitis/diagnóstico , Rinitis/epidemiología , Rinitis/complicaciones , Asma/diagnóstico , Asma/epidemiología , Asma/etiología , Rinitis Alérgica/complicaciones , Alérgenos , MultimorbilidadRESUMEN
OBJECTIVE: This study aimed to evaluate the efficacy and safety of oral ultra-low-dose continuous combination of 17ß-estradiol (17ß-E2) and norethisterone acetate (NETA) in postmenopausal Brazilian women. METHODS: Postmenopausal women (age 45-60 years) with amenorrhea >12 months and intact uterus, with moderate to severe vasomotor symptoms, were included. The vasomotor symptoms and endometrial bleeding were evaluated by a daily diary for 24 weeks, and the women were assessed at baseline and endpoint. RESULTS: A total of 118 women were included. The group treated with 0.5 mg 17ß-E2/0.1 mg NETA (n = 58) showed a percentage reduction of 77.1% in the frequency of vasomotor symptoms versus 49.9% in the placebo group (n = 60) (p = 0.0001). The severity score showed a reduction in the treatment group when compared to the placebo (p < 0.0001). The adverse events were comparable between the groups; however, in the 0.5 mg 17ß-E2/0.1 mg NETA group there were more complaints of vaginal bleeding; despite that, in most cycles in both treatment groups, more than 80% of women experienced amenorrhea. CONCLUSIONS: The combination of 0.5 mg 17ß-E2/0.1 mg NETA in a continuous combination regimen was shown to be effective in reducing the frequency and severity of vasomotor symptoms in Brazilian postmenopausal women.
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Estradiol , Noretindrona , Femenino , Humanos , Persona de Mediana Edad , Amenorrea , Brasil , Método Doble Ciego , Estradiol/efectos adversos , Terapia de Reemplazo de Estrógeno , Noretindrona/efectos adversos , Acetato de Noretindrona/efectos adversos , PosmenopausiaRESUMEN
Apoptosis is the best-known programmed cell death that maintains tissue homeostasis in eukaryotic cells. The morphological characteristics include nuclear and cytoplasmic contraction and cytoplasmic blebbing, its biochemical hallmarks include caspase protease activity and DNA fragmentation. In rat ovaries, cell death is a normal process that occurs throughout the organism's life. Granulosa cells, the more abundant cell type forming the ovarian follicles, are eliminated via different routes of cell death. Most granulosa cells are eliminated through apoptotic cell death. In this work, we analyzed the behavior of nuclear components throughout the apoptotic process and determined how they are regionalized and conserved during follicular atresia in rat ovaries. Apoptosis was detected based on caspase-3 activity and DNA fragmentation using the TUNEL technique. We identified the transcription markers H3ac and RNA Pol II, and splicing factor SC35 by immunodetection. The nucleolar components were analyzed via light microscopy and transmission electron microscopy through immunodetection of the proteins nucleolin and nucleophosmin-1. The nuclear ultrastructure was analyzed using standard contrast and preferential ribonucleoprotein contrast. Our results demonstrate that during the progression of apoptosis, chromatin is remodeled to constitute apoptotic bodies; transcription and spliceosome elements are reorganized along with the nucleolar components. Additionally, the splicing and transcription factors are segregated into specific territories inside the apoptotic bodies, suggesting that transcriptional elements are reorganized during the apoptotic process. Our results indicate that apoptotic bodies not only are compacted, and chromatin degraded but all the nuclear components are progressively reorganized during cell elimination; moreover, the transcriptional components are preserved.
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Apoptosis , Atresia Folicular , Animales , Apoptosis/genética , Cromatina/genética , Femenino , Atresia Folicular/metabolismo , Etiquetado Corte-Fin in Situ , Factores de Empalme de ARN , RatasRESUMEN
BACKGROUND: Despite the importance of tumor-infiltrating T lymphocytes (TILs) in cancer biology, the relationship between TIL phenotypes and their prognostic relevance for localized non-small-cell lung cancer (NSCLC) has not been well established. PATIENTS AND METHODS: Fresh tumor and normal adjacent tissue was prospectively collected from 150 patients with localized NSCLC. Tissue was comprehensively characterized by high-dimensional flow cytometry of TILs integrated with immunogenomic data from multiplex immunofluorescence, T-cell receptor sequencing, exome sequencing, RNA sequencing, targeted proteomics, and clinicopathologic features. RESULTS: While neither the magnitude of TIL infiltration nor specific TIL subsets were significantly prognostic alone, the integration of high-dimensional flow cytometry data identified two major immunotypes (IM1 and IM2) that were predictive of recurrence-free survival independent of clinical characteristics. IM2 was associated with poor prognosis and characterized by the presence of proliferating TILs expressing cluster of differentiation 103, programmed cell death protein 1, T-cell immunoglobulin and mucin-domain containing protein 3, and inducible T-cell costimulator. Conversely, IM1 was associated with good prognosis and differentiated by an abundance of CD8+ T cells expressing cytolytic enzymes, CD4+ T cells lacking the expression of inhibitory receptors, and increased levels of B-cell infiltrates and tertiary lymphoid structures. While increased B-cell infiltration was associated with good prognosis, the best prognosis was observed in patients with tumors exhibiting high levels of both B cells and T cells. These findings were validated in patient tumors from The Cancer Genome Atlas. CONCLUSIONS: Our study suggests that although the number of infiltrating T cells is not associated with patient survival, the nature of the infiltrating T cells, resolved in distinct TIL immunotypes, is prognostically relevant in NSCLC and may inform therapeutic approaches to clinical care.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Linfocitos T CD8-positivos , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/patología , Linfocitos Infiltrantes de Tumor/patología , PronósticoRESUMEN
BACKGROUND: Proper identification of patients at risk of developing serious disease in the context of SARS-CoV-2 infection, as well as the initiation of early treatment, is one of the fundamental elements for successful management of COVID-19. The main objective of this study was to evaluate the usefulness of serum biomarkers (neutrophils, lymphocytes, C-reactive protein, lactate dehydrogenase, D-dimer, ferritin, and interleukin-6) to predict the early response to immunosuppressant therapy in COVID-19 patients. METHODS: This is a case-control study nested in a retrospective cohort, which included hospitalized patients with interstitial pneumonia and with elevation of some proinflammatory parameters. Each of the individuals who died during the 28-day follow-up was defined as a case. For each case, 4 controls were selected, matched by age, gender, and comorbidities. RESULTS: The initial cohort included 856 patients. The incidence of therapeutic failure in the cohort was 14%, thus we identified a total of 120 cases. After the application of a Cox regression model, high serum concentrations of LDH (> 451 IU/L), ferritin (> 1,014 ng/mL) and D-Dimer (> 1,300 ng/mL) were identified as predictors of poor response to treatment. Highly-specific cut-off points could not be established for any of these biomarkers. CONCLUSIONS: Some inflammatory biomarkers, such as LDH, ferritin, and D-dimer, may be helpful in identifying patients for whom an early immunomodulatory therapeutic intervention should be considered in the treatment of COVID-19 patients with pneumonia.
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Tratamiento Farmacológico de COVID-19 , Biomarcadores , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Ferritinas , Humanos , Factores Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Interleucina-6 , L-Lactato Deshidrogenasa , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Conflicting results have been obtained through meta-analyses for the role of obesity as a risk factor for adverse outcomes in patients with coronavirus disease-2019 (COVID-19), possibly due to the inclusion of predominantly multimorbid patients with severe COVID-19. Here, we aimed to study obesity alone or in combination with other comorbidities as a risk factor for short-term all-cause mortality and other adverse outcomes in Mexican patients evaluated for suspected COVID-19 in ambulatory units and hospitals in Mexico. We performed a retrospective observational analysis in a national cohort of 71 103 patients from all 32 states of Mexico from the National COVID-19 Epidemiological Surveillance Study. Two statistical models were applied through Cox regression to create survival models and logistic regression models to determine risk of death, hospitalisation, invasive mechanical ventilation, pneumonia and admission to an intensive care unit, conferred by obesity and other comorbidities (diabetes mellitus (DM), chronic obstructive pulmonary disease, asthma, immunosuppression, hypertension, cardiovascular disease and chronic kidney disease). Models were adjusted for other risk factors. From 24 February to 26 April 2020, 71 103 patients were evaluated for suspected COVID-19; 15 529 (21.8%) had a positive test for SARS-CoV-2; 46 960 (66.1%), negative and 8614 (12.1%), pending results. Obesity alone increased adjusted mortality risk in positive patients (hazard ratio (HR) = 2.7, 95% confidence interval (CI) 2.04-2.98), but not in negative and pending-result patients. Obesity combined with other comorbidities further increased risk of death (DM: HR = 2.79, 95% CI 2.04-3.80; immunosuppression: HR = 5.06, 95% CI 2.26-11.41; hypertension: HR = 2.30, 95% CI 1.77-3.01) and other adverse outcomes. In conclusion, obesity is a strong risk factor for short-term mortality and critical illness in Mexican patients with COVID-19; risk increases when obesity is present with other comorbidities.
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COVID-19/mortalidad , Obesidad/complicaciones , Adulto , COVID-19/complicaciones , COVID-19/epidemiología , Estudios de Cohortes , Femenino , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Obesidad/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
We compared sediment quality in estuaries at three locations along the coast of São Paulo State, Brazil, using geochemical analyses and whole sediment toxicity tests, during the southern summer and winter of 2013. Each locality is afforded a distinct degree of legal protection, and exhibits a different level of metal pollution: overall, Rio Diana (RD, the most polluted, a Permanent Protection Area) > Rio Itapanhaú (RI, intermediate contamination, an Environmental Protection Area) > Rio Picinguaba (RP, pristine, a State Park). Chronic sediment toxicity tests evaluated reproductive rates of the copepod Nitokra sp. RI sediments showed the highest metal concentrations and toxicity in both seasons. Metal concentrations at RD were low but toxic in summer. RP sediments were not contaminated, suggesting effective legal protection from pollution at this locality. RI and RD, although provided some legal protection, showed clear signs of environmental degradation, emphasizing the need for more effective pollution control.
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Sedimentos Geológicos , Contaminantes Químicos del Agua , Animales , Brasil , Ecotoxicología , Monitoreo del Ambiente , Estuarios , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidadRESUMEN
The correlation length ξ, a key quantity in glassy dynamics, can now be precisely measured for spin glasses both in experiments and in simulations. However, known analysis methods lead to discrepancies either for large external fields or close to the glass temperature. We solve this problem by introducing a scaling law that takes into account both the magnetic field and the time-dependent spin-glass correlation length. The scaling law is successfully tested against experimental measurements in a CuMn single crystal and against large-scale simulations on the Janus II dedicated computer.
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BACKGROUND AND PURPOSE: It is challenging to assess patients with blepharospasm (BSP) and hemifacial spasm (HFS) as these patients exhibit a wide range of amplitudes of eyelid movements. In order to quantify these movements, a mathematical algorithm, i.e. Fast Fourier Transform, can be employed to convert the signal from the time domain to the frequency domain. The result of this quantification represents the energy generated during the eyelid movements. In order to objectively assess the therapeutic effects of botulinum toxin (BoNT) in these patients, we evaluated the energy generated by the upper eyelid during spontaneous eyelid movements before and after treatment. METHODS: A total of 39 patients with BSP and HFS were evaluated before and 30 days after receiving onabotulinum toxin A injections. A high-speed camera and micro light-emitting diodes were used to register the spontaneous eyelid movements. The result of the quantification obtained using Fast Fourier Transform permitted assessment of the activity associated with the eyelid movements. RESULTS: We studied 78 eyelids. The total energy generated during spontaneous eyelid movements was significantly reduced after treatment in the patients with BSP (P = 0.0018) and on the affected side in the patients with HFS (P = 0.0058). CONCLUSIONS: The assessment of the energy generated by the upper eyelid during spontaneous eyelid movements enabled us to measure the therapeutic effects of BoNT in patients with these conditions. The use of this system could enable customized and fine adjustments to BoNT doses based on each patient's needs.
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Blefaroespasmo , Espasmo Hemifacial , Blefaroespasmo/tratamiento farmacológico , Toxinas Botulínicas Tipo A , Movimientos Oculares , Párpados , Espasmo Hemifacial/tratamiento farmacológico , HumanosRESUMEN
Most of the existing prediction models for COVID-19 lack validation, are inadequately reported or are at high risk of bias, a reason which has led to discourage their use. Few existing models have the potential to be extensively used by healthcare providers in low-resource settings since many require laboratory and imaging predictors. Therefore, we sought to develop and validate a multivariable prediction model of death in Mexican patients with COVID-19, by using demographic and patient history predictors. We conducted a national retrospective cohort study in two different sets of patients from the Mexican COVID-19 Epidemiologic Surveillance Study. Patients with a positive reverse transcription-polymerase chain reaction for SARS-CoV-2 and complete unduplicated data were eligible. In total, 83 779 patients were included to develop the scoring system through a multivariable Cox regression model; 100 000, to validate the model. Eight predictors (age, sex, diabetes, chronic obstructive pulmonary disease, immunosuppression, hypertension, obesity and chronic kidney disease) were included in the scoring system called PH-Covid19 (range of values: -2 to 25 points). The predictive model has a discrimination of death of 0.8 (95% confidence interval (CI) 0.796-0.804). The PH-Covid19 scoring system was developed and validated in Mexican patients to aid clinicians to stratify patients with COVID-19 at risk of fatal outcomes, allowing for better and efficient use of resources.
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COVID-19/mortalidad , Comorbilidad , Predicción/métodos , Medición de Riesgo/métodos , Prueba de Ácido Nucleico para COVID-19 , Humanos , México/epidemiología , Modelos Teóricos , Pandemias , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2/aislamiento & purificaciónRESUMEN
Wheat blast is a devastating disease caused by the Triticum pathotype of Magnaporthe oryzae. M. oryzae Triticum is capable of infecting leaves and spikes of wheat. Although symptoms of wheat spike blast (WSB) are quite distinct in the field, symptoms on leaves (WLB) are rarely reported because they are usually inconspicuos. Two field experiments were conducted in Bolivia to characterize the change in WLB and WSB intensity over time and determine whether multispectral imagery can be used to accurately assess WSB. Disease progress curves (DPCs) were plotted from WLB and WSB data, and regression models were fitted to describe the nature of WSB epidemics. WLB incidence and severity changed over time; however, the mean WLB severity was inconspicuous before wheat began spike emergence. Overall, both Gompertz and logistic models helped to describe WSB intensity DPCs fitting classic sigmoidal shape curves. Lin's concordance correlation coefficients were estimated to measure agreement between visual estimates and digital measurements of WSB intensity and to estimate accuracy and precision. Our findings suggest that the change of wheat blast intensity in a susceptible host population over time does not follow a pattern of a monocyclic epidemic. We have also demonstrated that WSB severity can be quantified using a digital approach based on nongreen pixels. Quantification was precise (0.96 < r> 0.83) and accurate (0.92 < ρ > 0.69) at moderately low to high visual WSB severity levels. Additional sensor-based methods must be explored to determine their potential for detection of WLB and WSB at earlier stages.
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Magnaporthe , Modelos Estadísticos , Imagen Óptica , Triticum , Bolivia , Magnaporthe/fisiología , Enfermedades de las Plantas/microbiología , Factores de Tiempo , Triticum/microbiologíaRESUMEN
BACKGROUND: Mental health trusts in England were expected to become completely smoke-free and embed smoking cessation practices by 2018. Such policies are fraught with concerns and have received mixed support from mental health staff. Understanding staff attitudes to these practices prior to enforcement of the policy could help design an effective implementation strategy. METHODS: A cross-sectional survey was conducted with clinical and non-clinical staff in a Mental Health Trust to understand smoking cessation practices and attitudes to the implementation of a completely smoke-free policy. RESULTS: There were 631 responses. Most participants disagreed with the policy on wards (59.6%) and throughout all mental health settings (57.4%). Clinicians expressed significantly lower organizational policy support (P = 0.001) than non-clinicians (P = 0.001). Psychiatrists were more supportive of the organizational items than nurses and allied health professionals. Clinicians' attitudes towards smoking cessation practices were less positive for those who were current smokers (P < 0.001), but more positive for clinicians who had received or were interested in attending smoking cessation training (P < 0.001). CONCLUSIONS: Partial and completely smoke-free policies remain unsupported by staff in mental health settings. Smoking cessation training appears to reinforce rather than alter attitudes towards smoking cessation.
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Política para Fumadores , Cese del Hábito de Fumar , Actitud del Personal de Salud , Estudios Transversales , Inglaterra , Humanos , Salud MentalRESUMEN
The consumption of probiotic-enriched dairy products has been associated with many health benefits, including anti-hyperglycemic activity. The effect on health is dependent on the type of probiotic culture used and the dairy product consumed. This study evaluated the effect of different probiotic-enriched dairy matrices (Minas Frescal cheese, Prato cheese, and whey dairy beverage) containing Lactobacillus casei on in vitro and in vivo anti-hyperglycemic activity. For this purpose, in vitro anti-hyperglycemic activity was determined by the inhibition of α-glucosidase and α-amylase activities, and a human study was performed with healthy individuals (n = 15, consumption of bread as a control; bread + Minas Frescal cheese; bread + Prato cheese; bread + dairy beverage) to assess the effects of different probiotic foods on postprandial glycemia. In vitro data showed that Prato cheese presented the highest lipid (36.9 g/100 g) and protein (26.5 g/100 g) contents as well as the highest α-amylase (60.7%) and α-glucosidase (52.6%) inhibition. The consumption of Prato cheese resulted in a lesser increase in blood glucose level (13 mg/dL) compared with the consumption of bread alone (19 mg/dL), Minas Frescal cheese (20 mg/dL), and whey dairy beverage (30 mg/dL), with glycemic indices similar to that observed for the control. The present results demonstrated a good correlation between in vitro and in vivo data, in which the type of dairy matrix affects the anti-hyperglycemic activity. It is concluded that the consumption of probiotic Prato cheese can contribute to the reduction of postprandial glycemia in healthy individuals.
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Glucemia/metabolismo , Productos Lácteos , Hiperglucemia/prevención & control , Periodo Posprandial , Probióticos , Adulto , Animales , Queso , Femenino , Índice Glucémico , Humanos , Hiperglucemia/sangre , Lacticaseibacillus casei/metabolismo , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Tar spot of corn has been a major foliar disease in several Latin American countries since 1904. In 2015, tar spot was first documented in the United States and has led to significant yield losses of approximately 4.5 million t. Tar spot is caused by an obligate pathogen, Phyllachora maydis, and thus requires a living host to grow and reproduce. Due to its obligate nature, biological and epidemiological studies are limited and impact of disease in corn production has been understudied. Here we present the current literature and gaps in knowledge of tar spot of corn in the Americas, its etiology, distribution, impact and known management strategies as a resource for understanding the pathosystem. This will in tern guide current and future research and aid in the development of effective management strategies for this disease.
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Enfermedades de las Plantas , Zea mays , Américas , Estados UnidosRESUMEN
The environmental quality of a Ramsar wetland site located at the Cananéia-Iguape-Peruíbe Protected Area (CIP-PA), in São Paulo, Brazil, was assessed by geochemical analyses and biomarker assessments (GPx, GST, GSH, GST, MT, LPO, DNA damage) performed in swimming crab Callinectes danae Smith, 1869 organs (posterior and anterior gills and hepatopancreas) to estimate sediment contaminant bioavailability. The results indicated that two sampling stations, PT and PM, exhibited the worst environmental conditions, as sediments collected at both points contained metal contamination, while crabs exhibited significant responses for GPx, GST, and LPO (mostly during winter). Sediment contamination tended to be associated to fine sediments (both seasons) and organic matter (winter). During the summer survey, Pb concentrations in sediments of station PT exceeded the Brazilian Sediment Quality Guidelines (SQGs) and the Canadian Interim Marine Sediment Quality Guidelines. Metal concentrations in sediments sampled in winter were higher compared with summer, with Co, Ni, and Pb exceeding SQGs levels at PT, whereas Co, Ni, Hg, Zn, and Pb exceeded SQGs at PM. Biomarker induction during summer appeared to be caused by natural variables (water salinity and temperature, and molting cycle), whereas oxidative stress and tissue damage during winter appeared to be more clearly linked to metal contamination. Anterior gills presented the clearest signs of seasonal variability, being more responsive to sediment contamination. The results suggest that metals originated from the upper Ribeira de Iguape River are transported toward the estuarine system, causing effects on C. danae individuals. Additionally, seasonality is a strong factor concerning CIP-PA toxicity, since the rainfall regime significantly modifies the freshwater flow and, consequently, estuarine water salinity, suspended particle and metal inputs, as well as the location of depositional areas. Thus, efforts to mitigate CIP-PA contamination should be based on the control of upstream pollution sources.
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Monitoreo Biológico/métodos , Braquiuros/efectos de los fármacos , Biomarcadores Ambientales/efectos de los fármacos , Sedimentos Geológicos/química , Metales Pesados/análisis , Contaminantes Químicos del Agua/análisis , Humedales , Animales , Braquiuros/metabolismo , Brasil , Branquias/química , Branquias/metabolismo , Hepatopáncreas/química , Hepatopáncreas/metabolismo , Metales Pesados/toxicidad , Ríos/química , Estaciones del Año , Contaminantes Químicos del Agua/toxicidadRESUMEN
OBJECTIVE: To investigate the impact of deleting Suppressor of Cytokine Signaling (SOCS)-3 (SOCS3) in chondrocytes during murine skeletal development. METHOD: Mice with a conditional Socs3 allele (Socs3fl/fl) were crossed with a transgenic mouse expressing Cre recombinase under the control of the type II collagen promoter (Col2a1) to generate Socs3Δ/Δcol2 mice. Skeletal growth was analyzed over the lifespan of Socs3Δ/Δcol2 mice and controls by detailed histomorphology. Bone size and cortical bone development was evaluated by micro-computed tomography (micro-CT). Growth plate (GP) zone width, chondrocyte proliferation and apoptosis were assessed by immunofluorescence staining for Ki67 and TUNEL. Fibroblast growth factor receptor-3 (FGFR3) signaling in the GP was assessed by immunohistochemistry, while the effect of SOCS3 overexpression on FGFR3-driven pMAPK signaling in HEK293T cells was evaluated by Western blot. RESULTS: Socs3Δ/Δcol2 mice of both sexes were consistently smaller compared to littermate controls throughout life. This phenotype was due to reduced long bone size, poor cortical bone development, reduced Ki67+ proliferative chondrocytes and decreased proliferative zone (PZ) width in the GP. Expression of pMAPK, but not pSTAT3, was increased in the GPs of Socs3Δ/Δcol2 mice relative to littermate controls. Overexpression of FGFR3 in HEK293T cells increased Fibroblast Growth Factor 18 (FGF18)-dependent Mitogen-activated protein kinase (MAPK) phosphorylation, while concomitant expression of SOCS3 reduced FGFR3 expression and abrogated MAPK signaling. CONCLUSION: Our results suggest a potential role for SOCS3 in GP chondrocyte proliferation by regulating FGFR3-dependent MAPK signaling in response to FGF18.
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Desarrollo Óseo/fisiología , Condrocitos/fisiología , Proteínas Quinasas Activadas por Mitógenos/fisiología , Proteína 1 Supresora de la Señalización de Citocinas/fisiología , Animales , Femenino , Masculino , Ratones , Ratones Transgénicos , Transducción de SeñalRESUMEN
This study was aimed at developing a new functional fermented beverage manufactured with semi-skimmed sheep milk and strawberry pulp (Fragaria × ananassa Duch.) and commercial prebiotic ingredients. We also compared the performance of the yogurt starter cultures and a Lactobacillus plantarum strain (CECT_8328) with potential probiotic properties. We assessed the nutritional profile, bioactivity compounds, viability of lactic acid bacteria during storage, and survival of L. plantarum after in vitro simulated digestion during the storage period. The lactic acid bacteria were viable throughout the storage period, but only L. plantarum maintained good viability after simulated digestion. Nevertheless, neither inulin nor potato starch increased bacterial viability. The fermented semi-skimmed sheep milk strawberry beverages we developed are good sources of minerals and proteins.
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Bebidas , Fragaria , Leche , Animales , Bebidas/microbiología , Proteínas en la Dieta , Fermentación , Inulina/metabolismo , Lactobacillales/metabolismo , Lactobacillus plantarum , Leche/metabolismo , Valor Nutritivo , Prebióticos , Probióticos , Ovinos , Yogur/microbiologíaRESUMEN
Fermented whey dairy beverages are dairy products obtained by fermentation from a mixture of milk and whey. These beverages have important health benefits, which could be improved with the addition of probiotic cultures. This study assessed the protective effect of the cosupplementation of a probiotic culture (Lactobacillus casei 01) with a fermented whey dairy beverage against infection by Salmonella enterica ssp. enterica serovar Typhimurium in a murine model. Two fermented whey dairy beverages were prepared: conventional (FWB; starter culture) and probiotic (PFWB; starter and probiotic cultures). In the first set of experiments, Balb/C female mice were treated with FWB or PFWB, challenged with Salmonella Typhimurium, and analyzed for clinical signs, weight loss, and mortality for 20 d postinfection. In the second set of experiments, mice were treated with FWB or PFWB, challenged with Salmonella Typhimurium, and killed on d 10 postinfection. The liver, colon, and ileum were used for myeloperoxidase, eosinophil peroxidase, and histological analysis and translocation to the liver. The contents from the small intestine were used for secretory IgA determination. The FWB treatment showed a better effect on animal survival (70%), translocation of the pathogen to the liver (2 out of 10), histopathology (fewer lesions), and inflammation than PFWB, which presented 50% animal survival, translocation in 5 out of 10 animals, and higher lesions. The control group presented 40% animal survival, translocation in 6 out of 10 animals, and severe lesions. Therefore, FWB was deemed to have a greater protective effect against Salmonella Typhimurium infection in the murine model compared with PFWB.