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1.
Rev Med Inst Mex Seguro Soc ; 61(5): 559-566, 2023 Sep 04.
Artigo em Espanhol | MEDLINE | ID: mdl-37756704

RESUMO

Background: The lockdown derived from the declaration of a pandemic due to SARS-CoV-2 in March 2020 by the World Health Organization altered daily activities, including the academic ones, which were adapted to virtuality. In Ecuador, the new modality of study had an increase in the use of electronic devices that triggered new problems. Objective: To stablish the prevalence of depression and anxiety among medical students from the Universidad Central del Ecuador (Central University of Ecuador) in virtual education during the COVID-19 pandemic. Material and methods: Cross-sectional analytic study conducted between June and July of 2021 in students from first to tenth semester during virtual education. All studied subjects were evaluated using an electronic survey, depression and anxiety variables were assessed with the BDI-II and GAD-7 scales, respectively. In addition, sociodemographic data were collected, including the family APGAR. A response rate of 63.3% (1528 students) was obtained. Results: Overall prevalence of depression was 37.8% and the prevalence of anxiety 30.3%. Lower-years students were the most affected by these pathologies. The protective factors found were physical activity and psychological support in religion, whereas the main risk factors found were a dysfunctional family, lack of an exclusive study space and low academic performance. Furthermore, the frequency of depression and anxiety was significantly higher in women. Conclusion: The virtual modality showed a high prevalence of depression and anxiety in medical students.


Introducción: el confinamiento derivado de la declaración de pandemia por SARS-CoV-2 en marzo de 2020 por la Organización Mundial de la Salud alteró las actividades diarias, incluidas las académicas, que se adaptaron a la virtualidad. En Ecuador, la nueva modalidad de estudio tuvo un aumento del uso de dispositivos electrónicos que desencadenó nuevos problemas. Objetivo: determinar la prevalencia de depresión y ansiedad en estudiantes de medicina de la Universidad Central del Ecuador en el ciclo de educación virtual durante la pandemia por COVID-19. Material y métodos: estudio analítico transversal realizado entre junio y julio de 2021 en estudiantes de medicina de primero a décimo semestre durante la educación virtual. Por medio de una encuesta electrónica enviada a todos los sujetos de estudio, se evaluaron las variables depresión y ansiedad mediante las escalas BDI-II y GAD-7 respectivamente. Además, se recopilaron datos sociodemográficos, incluido el APGAR familiar. Se obtuvo una tasa de respuesta del 63.3% (1528 estudiantes). Resultados: la prevalencia de depresión fue de 37.8% y la de ansiedad 30.3%. Los estudiantes de años inferiores fueron los más afectados. Los factores protectores fueron la actividad física y el apoyo psicológico en la religión, mientras que los factores de riesgo fueron tener una familia disfuncional, la ausencia de un espacio exclusivo de estudio y un bajo rendimiento académico. Asimismo, la frecuencia de depresión y ansiedad fue significativamente superior en mujeres. Conclusión: durante la modalidad virtual se observó una alta prevalencia de sintomatología de depresión y ansiedad en estudiantes de medicina.


Assuntos
COVID-19 , Estudantes de Medicina , Feminino , Humanos , Pandemias , Estudos Transversais , Depressão/epidemiologia , Depressão/etiologia , COVID-19/epidemiologia , SARS-CoV-2 , Controle de Doenças Transmissíveis , Ansiedade/epidemiologia , Ansiedade/etiologia , Estresse Psicológico , Universidades
2.
Sci Adv ; 9(35): eadg5234, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37656787

RESUMO

N6-methyladenosine (m6A) is the most abundant modification on messenger RNAs (mRNAs) and is catalyzed by methyltransferase-like protein 3 (Mettl3). To understand the role of m6A in a self-renewing somatic tissue, we deleted Mettl3 in epidermal progenitors in vivo. Mice lacking Mettl3 demonstrate marked features of dysfunctional development and self-renewal, including a loss of hair follicle morphogenesis and impaired cell adhesion and polarity associated with oral ulcerations. We show that Mettl3 promotes the m6A-mediated degradation of mRNAs encoding critical histone modifying enzymes. Depletion of Mettl3 results in the loss of m6A on these mRNAs and increases their expression and associated modifications, resulting in widespread gene expression abnormalities that mirror the gross phenotypic abnormalities. Collectively, these results have identified an additional layer of gene regulation within epithelial tissues, revealing an essential role for m6A in the regulation of chromatin modifiers, and underscoring a critical role for Mettl3-catalyzed m6A in proper epithelial development and self-renewal.


Assuntos
Histonas , Metiltransferases , Animais , Camundongos , Metiltransferases/genética , Adenosina , Adesão Celular , RNA Mensageiro , Catálise
3.
Nat Microbiol ; 8(8): 1587-1599, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37443277

RESUMO

LY6E is an antiviral restriction factor that inhibits coronavirus spike-mediated fusion, but the cell types in vivo that require LY6E for protection from respiratory coronavirus infection are unknown. Here we used a panel of seven conditional Ly6e knockout mice to define which Ly6e-expressing cells confer control of airway infection by murine coronavirus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Loss of Ly6e in Lyz2-expressing cells, radioresistant Vav1-expressing cells and non-haematopoietic cells increased susceptibility to murine coronavirus. Global conditional loss of Ly6e expression resulted in clinical disease and higher viral burden after SARS-CoV-2 infection, but little evidence of immunopathology. We show that Ly6e expression protected secretory club and ciliated cells from SARS-CoV-2 infection and prevented virus-induced loss of an epithelial cell transcriptomic signature in the lung. Our study demonstrates that lineage confined rather than broad expression of Ly6e sufficiently confers resistance to disease caused by murine and human coronaviruses.


Assuntos
COVID-19 , Humanos , Camundongos , Animais , SARS-CoV-2/metabolismo , Pulmão , Antivirais/farmacologia , Células Epiteliais/metabolismo , Camundongos Knockout , Antígenos de Superfície/metabolismo , Proteínas Ligadas por GPI
5.
PLoS One ; 18(2): e0275546, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36787303

RESUMO

In mathematical epidemiology, it is usual to implement compartmental models to study the transmission of diseases, allowing comprehension of the outbreak dynamics. Thus, it is necessary to identify the natural history of the disease and to establish promissory relations between the structure of a mathematical model, as well as its parameters, with control-related strategies (real interventions) and relevant socio-cultural behaviors. However, we identified gaps between the model creation and its implementation for the use of decision-makers for policy design. We aim to cover these gaps by proposing a discrete mathematical model with parameters having intuitive meaning to be implemented to help decision-makers in control policy design. The model considers novel contagion probabilities, quarantine, and diffusion processes to represent the recovery and mortality dynamics. We applied mathematical model for COVID-19 to Colombia and some of its localities; moreover, the model structure could be adapted for other diseases. Subsequently, we implemented it on a web platform (MathCOVID) for the usage of decision-makers to simulate the effect of policies such as lock-downs, social distancing, identification in the contagion network, and connectivity among populations. Furthermore, it was possible to assess the effects of migration and vaccination strategies as time-dependent inputs. Finally, the platform was capable of simulating the effects of applying one or more policies simultaneously.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Colômbia/epidemiologia , Controle de Doenças Transmissíveis , Política Pública
6.
bioRxiv ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36747632

RESUMO

LY6E is an antiviral protein that inhibits coronavirus entry. Its expression in immune cells allows mice to control murine coronavirus infection. However, it is not known which immune cell subsets mediate this control or whether LY6E protects mice from SARS-CoV-2. In this study, we used tissue-specific Cre recombinase expression to ablate Ly6e in distinct immune compartments or in all epiblast-derived cells, and bone marrow chimeras to target Ly6e in a subset of radioresistant cells. Mice lacking Ly6e in Lyz2 -expressing cells and radioresistant Vav1 -expressing cells were more susceptible to lethal murine coronavirus infection. Mice lacking Ly6e globally developed clinical disease when challenged with the Gamma (P.1) variant of SARS-CoV-2. By contrast, wildtype mice and mice lacking type I and type III interferon signaling had no clinical symptoms after SARS-CoV-2 infection. Transcriptomic profiling of lungs from SARS-CoV-2-infected wildtype and Ly6e knockout mice revealed a striking reduction of secretory cell-associated genes in infected knockout mice, including Muc5b , an airway mucin-encoding gene that may protect against SARS-CoV-2-inflicted respiratory disease. Collectively, our study reveals distinct cellular compartments in which Ly6e confers cell intrinsic antiviral effects, thereby conferring resistance to disease caused by murine coronavirus and SARS-CoV-2.

7.
Bull Math Biol ; 84(11): 127, 2022 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-36138179

RESUMO

Mathematical modeling is a tool used for understanding diseases dynamics. The discrete-time model is an especial case in modeling that satisfactorily describes the epidemiological dynamics because of the discrete nature of the real data. However, discrete models reduce their descriptive and fitting potential because of assuming a homogeneous population. Thus, in this paper, we proposed contagion probability functions according to two infection paradigms that consider factors associated with transmission dynamics. For example, we introduced probabilities of establishing an infectious interaction, the number of contacts with infectious and the level of connectivity or social distance within populations. Through the probabilities design, we overcame the homogeneity assumption. Also, we evaluated the proposed probabilities through their introduction into discrete-time models for two diseases and different study zones with real data, COVID-19 for Germany and South Korea, and dengue for Colombia. Also, we described the oscillatory dynamics for the last one using the contagion probabilities alongside parameters with a biological sense. Finally, we highlight the implementation of the proposed probabilities would improve the simulation of the public policy effect of control strategies over an infectious disease outbreak.


Assuntos
COVID-19 , Modelos Biológicos , COVID-19/epidemiologia , Simulação por Computador , Humanos , Funções Verossimilhança , Conceitos Matemáticos , Probabilidade
8.
Cells ; 11(14)2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35883582

RESUMO

(1) Background: Renal immune cells and lymphatic vessel (LV) density have been reported previously to be increased in multiple mouse models of hypertension (HTN). However, whether interstitial levels of HTN stimuli such as angiotensin II, salt, or asymmetric dimethylarginine have a direct or indirect effect on lymphangiogenesis is unknown. We hypothesized that these 3 HTN stimuli directly increase lymphatic endothelial cell (LEC) proliferation, LEC 3-D matrix invasion and vessel formation, and sprouting of mouse mesometrial LVs. (2) Methods: Human LECs (hLECs) and mouse LECs (mLECs) were treated with HTN stimuli while explanted mouse mesometrial LVs were treated with either the same HTN stimuli or with HTN stimuli-conditioned media. Conditioned media was prepared by treating murine splenocytes with HTN stimuli. (3) Results: HTN stimuli had no direct effect on hLEC or mLEC proliferation. Treatment of hLECs with HTN stimuli increased the number of lumen-forming structures and invasion distance (both p < 0.05) in the 3-D matrix but decreased the average lumen diameter and the number of cells per invading structure (both p < 0.05). Conditioned media from HTN-stimuli-treated splenocytes significantly attenuated the decrease in sprout number (aside from salt) and sprout length of mouse mesometrial LVs that is found in the HTN stimuli alone. (4) Conclusions: These data indicate that HTN stimuli indirectly prevent a decrease in lymphangiogenesis through secreted factors from HTN-stimuli-treated immune cells.


Assuntos
Hipertensão , Vasos Linfáticos , Animais , Meios de Cultivo Condicionados/farmacologia , Células Endoteliais , Humanos , Linfangiogênese , Camundongos
9.
Trop Med Infect Dis ; 8(1)2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36668912

RESUMO

Some deterministic models deal with environmental conditions and use parameter estimations to obtain experimental parameters, but they do not consider anthropogenic or environmental disturbances, e.g., chemical control or climatic conditions. Even more, they usually use theoretical or measured in-lab parameters without worrying about uncertainties in initial conditions, parameters, or changes in control inputs. Thus, in this study, we estimate parameters (including chemical control parameters) and confidence contours under uncertainty conditions using data from the municipality of Bello (Colombia) during 2010-2014, which includes two epidemic outbreaks. Our study shows that introducing non-periodic pulse inputs into the mathematical model allows us to: (i) perform parameter estimation by fitting real data of consecutive dengue outbreaks, (ii) highlight the importance of chemical control as a method of vector control, and (iii) reproduce the endemic behavior of dengue. We described a methodology for parameter and sub-contour box estimation under uncertainties and performed reliable simulations showing the behavior of dengue spread in different scenarios.

10.
Trop Med Infect Dis ; 8(1)2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36668937

RESUMO

Dengue is a disease of high interest for public health in the affected localities. Dengue virus is transmitted by Aedes species and presents hyperendemic behaviors in tropical and subtropical regions. Colombia is one of the countries most affected by the dengue virus in the Americas. Its central-west region is a hot spot in dengue transmission, especially the Department of Antioquia, which has suffered from multiple dengue outbreaks in recent years (2015-2016 and 2019-2020). In this article, we perform a retrospective analysis of the confirmed dengue cases in Antioquia, discriminating by both subregions and dengue severity from 2015 to 2020. First, we conduct an exploratory analysis of the epidemic data, and then a statistical survival analysis is carried out using a Cox regression model. Our findings allow the identification of the hazard and socio-demographic patterns of dengue infections in the Colombian subtropical region of Antioquia from 2015 to 2020.

11.
Rev Med Inst Mex Seguro Soc ; 59(6): 538-544, 2021 11 01.
Artigo em Espanhol | MEDLINE | ID: mdl-34910415

RESUMO

Background: University students are usually a risk group in terms of their sexual life, either because of social habits or because of the behavioral predisposers to which they are exposed. This article analyse the relationship between these factors. Objective: To establish the frequency and relationship between behavioral and social predisposers with active sexual life (ASL) in university students. Material and methods: Cross-sectional study, carried out in 360 medical students. The data of sexual life and the behavioral and social factors associated with it were analyzed through prevalences with their confidence intervals, as well as the calculation of the Odds Ratio (OR). Results: The results showed that 58.9% (95%CI: 53.7%-63.9%) of the students have ever had sexual intercourse. The only behavioral predisposing associated with ASL was the absence of religious practices (OR: 2.6; 95%CI: 1.6-4.1; p < 0.001), while all the habits and social behaviors analyzed were significantly associated with ASL, the most common being attendance at parties (77.8%) and the consumption of alcoholic beverages (67.2%). Conclusions: Our results show that young people present a wide range of behavioral and social characteristics that influence their sexual life, therefore, implementing strategies aimed at protecting sexual and reproductive health is also necessary in this age group.


Introducción: los estudiantes universitarios suelen ser un grupo de riesgo en cuanto a su vida sexual, ya sea por los hábitos sociales o por los predisponentes conductuales a los que se encuentran expuestos. Este artículo analiza la relación entre estos factores. Objetivo: establecer la frecuencia y relación entre predisponentes conductuales y sociales con la vida sexual activa (VSA) en estudiantes universitarios. Material y métodos: estudio transversal, realizado en 360 estudiantes de Medicina. Los datos de la vida sexual y los factores conductuales y sociales asociados a ella, se analizaron a través de prevalencias con sus intervalos de confianza, así como con el cálculo del Odds Ratio (OR). Resultados: los resultados mostraron que el 58.9% (IC95%: 53.7%-63.9%) de los estudiantes han tenido alguna vez relaciones sexuales. El único predisponente conductual que se asoció con la VSA fue la ausencia de prácticas religiosas (OR: 2.6; IC95%: 1.6-4.1; p < 0.001), mientras que todos los hábitos y conductas sociales analizados, se asociaron significativamente con la VSA, siendo los más comúnes la asistencia a fiestas (77.8%) y el consumo de bebidas alcohólicas (67.2%). Conclusiones: nuestros resultados muestran que los jóvenes presentan una amplia gama de características conductuales y sociales que influyen en su vida sexual, por lo que, el implementar estrategias orientadas a proteger la salud sexual y reproductiva también es necesario en este grupo etario.


Assuntos
Comportamento Sexual , Universidades , Adolescente , Estudos Transversais , Hábitos , Humanos , Estudantes , Inquéritos e Questionários
12.
Rev. Méd. Inst. Mex. Seguro Soc ; 59(6): 538-544, dic. 2021. tab
Artigo em Espanhol | LILACS | ID: biblio-1357556

RESUMO

Introducción: los estudiantes universitarios suelen ser un grupo de riesgo en cuanto a su vida sexual, ya sea por los hábitos sociales o por los predisponentes conductuales a los que se encuentran expuestos. Este artículo analiza la relación entre estos factores. Objetivo: establecer la frecuencia y relación entre predisponentes conductuales y sociales con la vida sexual activa (VSA) en estudiantes universitarios. Material y métodos: estudio transversal, realizado en 360 estudiantes de Medicina. Los datos de la vida sexual y los factores conductuales y sociales asociados a ella, se analizaron a través de prevalencias con sus intervalos de confianza, así como con el cálculo del Odds Ratio (OR). Resultados: los resultados mostraron que el 58.9% (IC95%: 53.7%-63.9%) de los estudiantes han tenido alguna vez relaciones sexuales. El único predisponente conductual que se asoció con la VSA fue la ausencia de prácticas religiosas (OR: 2.6; IC95%: 1.6-4.1; p < 0.001), mientras que todos los hábitos y conductas sociales analizados, se asociaron significativamente con la VSA, siendo los más comúnes la asistencia a fiestas (77.8%) y el consumo de bebidas alcohólicas (67.2%). Conclusiones: nuestros resultados muestran que los jóvenes presentan una amplia gama de características conductuales y sociales que influyen en su vida sexual, por lo que, el implementar estrategias orientadas a proteger la salud sexual y reproductiva también es necesario en este grupo etario.


Background: University students are usually a risk group in terms of their sexual life, either because of social habits or because of the behavioral predisposers to which they are exposed. This article analyse the relationship between these factors. Objective: To establish the frequency and relationship between behavioral and social predisposers with active sexual life (ASL) in university students. Material and methods: Cross-sectional study, carried out in 360 medical students. The data of sexual life and the behavioral and social factors associated with it were analyzed through prevalences with their confidence intervals, as well as the calculation of the Odds Ratio (OR). Results: The results showed that 58.9% (95%CI: 53.7%-63.9%) of the students have ever had sexual intercourse. The only behavioral predisposing associated with ASL was the absence of religious practices (OR: 2.6; 95%CI: 1.6-4.1; p < 0.001), while all the habits and social behaviors analyzed were significantly associated with ASL, the most common being attendance at parties (77.8%) and the consumption of alcoholic beverages (67.2%). Conclusions: Our results show that young people present a wide range of behavioral and social characteristics that influence their sexual life, therefore, implementing strategies aimed at protecting sexual and reproductive health is also necessary in this age group.


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Comportamento Sexual , Comportamento Social , Estudantes de Medicina , Estudos Transversais , Fatores Sociais , Consumo de Bebidas Alcoólicas , Estratégias de Saúde , Fatores Sociológicos
13.
J Chem Phys ; 155(19): 194702, 2021 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-34800953

RESUMO

An accurate atomistic treatment of aqueous solid-liquid interfaces necessitates the explicit description of interfacial water ideally via ab initio molecular dynamics simulations. Many applications, however, still rely on static interfacial water models, e.g., for the computation of (electro)chemical reaction barriers and focus on a single, prototypical structure. In this work, we systematically study the relation between density functional theory-derived static and dynamic interfacial water models with specific focus on the water-Pt(111) interface. We first introduce a general construction protocol for static 2D water layers on any substrate, which we apply to the low index surfaces of Pt. Subsequently, we compare these with structures from a broad selection of reference works based on the Smooth Overlap of Atomic Positions descriptor. The analysis reveals some structural overlap between static and dynamic water ensembles; however, static structures tend to overemphasize the in-plane hydrogen bonding network. This feature is especially pronounced for the widely used low-temperature hexagonal ice-like structure. In addition, a complex relation between structure, work function, and adsorption energy is observed, which suggests that the concentration on single, static water models might introduce systematic biases that are likely reduced by averaging over consistently created structural ensembles, as introduced here.

14.
Genes (Basel) ; 12(7)2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209046

RESUMO

Dynamic modifications on RNA, frequently termed both, "RNA epigenetics" and "epitranscriptomics", offer one of the most exciting emerging areas of gene regulation and biomedicine. Similar to chromatin-based epigenetic mechanisms, writers, readers, and erasers regulate both the presence and interpretation of these modifications, thereby adding further nuance to the control of gene expression. In particular, the most abundant modification on mRNAs, N6-methyladenosine (m6A), catalyzed by methyltransferase-like 3 (METTL3) has been shown to play a critical role in self-renewing somatic epithelia, fine-tuning the balance between development, differentiation, and cancer, particularly in the case of squamous cell carcinomas (SCCs), which in aggregate, outnumber all other human cancers. Along with the development of targeted inhibitors of epitranscriptomic modulators (e.g., METTL3) now entering clinical trials, the field holds significant promise for treating these abundant cancers. Here, we present the most current summary of this work, while also highlighting the therapeutic potential of these discoveries.


Assuntos
Adenosina/análogos & derivados , Diferenciação Celular , Células Epiteliais/patologia , Regulação da Expressão Gênica , Metiltransferases/genética , Neoplasias/patologia , Transcriptoma , Adenosina/química , Epigênese Genética , Células Epiteliais/metabolismo , Humanos , Metiltransferases/química , Metiltransferases/metabolismo , Neoplasias/genética , Neoplasias/metabolismo
15.
J Gerontol A Biol Sci Med Sci ; 76(12): 2107-2111, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34038541

RESUMO

Epigenetic age acceleration is considered a measure of biological aging based on genome-wide patterns of DNA methylation. Although age acceleration has been associated with the incidence of diseases and death, less is known about how it is related to lifestyle behaviors. Among 2316 women, we evaluate associations between self-reported alcohol consumption and various metrics of epigenetic age acceleration. Recent average alcohol consumption was defined as the mean number of drinks consumed per week within the past year; lifetime average consumption was estimated as the mean number of drinks per year drinking. Whole-blood genome-wide DNA methylation was measured with HumanMethylation450 BeadChips and used to assess 4 epigenetic clocks (Hannum, Horvath, PhenoAge, and GrimAge) and their corresponding metrics of epigenetic age acceleration (Hannum AgeAccel, Horvath AgeAccel, PhenoAgeAccel, and GrimAgeAccel). Although alcohol consumption showed little association with most age acceleration metrics, both lifetime and recent average consumption measures were positively associated with GrimAgeAccel (lifetime, per additional 135 drinks/year: ß = 0.30 years, 95% confidence interval [CI]: 0.11, 0.48, p = .002; recent, per additional 5 drinks/week: ß = 0.19 years, 95% CI: 0.01, 0.37, p = .04). In a mutually adjusted model, only average lifetime alcohol consumption remained associated with GrimAgeAccel (lifetime, per additional 135 drinks/year: ß = 0.27 years, 95% CI: 0.04, 0.50, p = .02; recent, per 5 additional drinks/week: ß = 0.05 years, 95% CI: -0.16, 0.26, p = .64). Although alcohol use does not appear to be strongly associated with biological age measured by most epigenetic clocks, lifetime average consumption is associated with higher biological age assessed by the GrimAge epigenetic clock.


Assuntos
Envelhecimento , Consumo de Bebidas Alcoólicas , Metilação de DNA , Epigênese Genética , Envelhecimento/genética , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/genética , Epigenômica , Feminino , Humanos
16.
Am J Epidemiol ; 190(6): 984-993, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33693587

RESUMO

Epigenetic clocks use DNA methylation to estimate biological age. Whether body composition and physical activity are associated with these clocks is not well understood. Using blood samples collected at enrollment (2003-2009) from 2,758 women in the US nationwide Sister Study, we calculated 6 epigenetic age acceleration metrics using 4 epigenetic clocks (Hannum, Horvath, PhenoAge, GrimAge). Recreational physical activity was self-reported, and adiposity measures were assessed by trained medical examiners (body mass index (BMI), waist-to-hip ratio (WtH), waist circumference). In cross-sectional analyses, all adiposity measures were associated with epigenetic age acceleration. The strongest association was for BMI and PhenoAge, a measure of biological age that correlates with chronic disease (BMI of ≥35.0 vs. 18.5-24.9, ß = 3.15 years, 95% confidence interval (CI): 2.41, 3.90; P for trend < 0.001). In a mutual-adjustment model, both were associated with PhenoAge age acceleration (BMI of ≥35.0 vs. 18.5-24.9, ß = 2.69 years, 95% CI: 1.90, 3.48; P for trend < 0.001; quartile 4 vs.1 WtH, ß = 1.00 years, 95% CI: 0.34, 1.65; P for trend < 0.008). After adjustment, physical activity was associated only with GrimAge (quartile 4 vs. 1, ß = -0.42 years, 95% CI: -0.70, -0.14; P for trend = 0.001). Physical activity attenuated the waist circumference associations with PhenoAge and GrimAge. Excess adiposity was associated with epigenetic age acceleration; physical activity might attenuate associations with waist circumference.


Assuntos
Envelhecimento/genética , Composição Corporal/genética , Epigênese Genética/fisiologia , Exercício Físico/fisiologia , Adiposidade/genética , Adulto , Idoso , Índice de Massa Corporal , Estudos Transversais , Metilação de DNA/fisiologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Estados Unidos , Circunferência da Cintura , Relação Cintura-Quadril
17.
Clin Sci (Lond) ; 134(24): 3237-3257, 2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33346358

RESUMO

Hypertension is one of the most prevalent diseases that leads to end organ damage especially affecting the heart, kidney, brain, and eyes. Numerous studies have evaluated the association between hypertension and impaired sexual health, in both men and women. The detrimental effects of hypertension in men includes erectile dysfunction, decrease in semen volume, sperm count and motility, and abnormal sperm morphology. Similarly, hypertensive females exhibit decreased vaginal lubrication, reduced orgasm, and several complications in pregnancy leading to fetal and maternal morbidity and mortality. The adverse effect of hypertension on male and female fertility is attributed to hormonal imbalance and changes in the gonadal vasculature. However, mechanistic studies investigating the impact of hypertension on gonads in more detail on a molecular basis remain scarce. Hence, the aim of the current review is to address and summarize the effects of hypertension on reproductive health, and highlight the importance of research on the effects of hypertension on gonadal inflammation and lymphatics.


Assuntos
Gônadas/fisiopatologia , Hipertensão/fisiopatologia , Inflamação/fisiopatologia , Linfangiogênese , Reprodução/fisiologia , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Gônadas/efeitos dos fármacos , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Inflamação/complicações , Reprodução/efeitos dos fármacos
18.
Preprint em Espanhol | SciELO Preprints | ID: pps-1076

RESUMO

In the Chinese city of Wuhan at the end of 2019, a new respiratory disease known as COVID-19 emerged, caused by the SARS-CoV-2 virus. This disease spreads rapidly worldwide and presents numerous infections and deaths; therefore, the World Health Organization upgraded its category from epidemic to pandemic because of alarming levels of spread, severity, and inaction. Given this situation, different areas of science have approached the study of this disease, among them is mathematical epidemiology through the modeling of the phenomenon; therefore, in this document, we performed a systematic review related to transmission models of COVID-19, specifically discrete models because of the daily report of infection cases around the world. We identified different important disease features implemented in the models, e.g., metapopulations, migration, quarantine, inclusion of latency, and incubation periods, among others. Also, we identified its basic structure, and we found that many papers directly used SIR and SEIR models with no modification, being an excessive simplification of the COVID-19 transmission phenomenon. Likewise, some authors highlighted an important problem during the application of mathematical models: the quality or absence of the daily case data in some affected countries. Finally, the mathematical models should be constantly updated together with the publication of research related to virology and epidemiology of the disease.


A finales del año 2019, en la ciudad china de Wuhan, emergió una nueva enfermedad respiratoria conocida como COVID-19 que es producida por el virus SARS-CoV-2, similar al virus causante del síndrome respiratorio agudo grave (SARS-CoV). Actualmente, esta enfermedad se esparció rápidamente a nivel mundial y ha presentado una gran cantidad de afectados en diferentes regiones del mundo; por lo tanto, la Organización Mundial de la Salud elevó su categoría de epidemia a pandemia debido a los niveles alarmantes de propagación, gravedad e inacción. Dada esta situación, diferentes áreas de la ciencia han abordado su estudio, entre ellas esta la epidemiología matemática a través del modelado del fenómeno; por lo tanto en el presente documento se realizó una revisión sistematizada de literatura relacionada a modelos de transmisión del COVID-19, específicamente modelos discretos debido a la naturaleza de reporte diaria de casos de la enfermedad en diferentes localidades del mundo. Se lograron identificar diferentes características importantes de la enfermedad que son implementadas en los modelos matemáticos: división por grupos etarios, metapoblaciones, migración, cuarentena, inclusión de periodos de latencia e incubación, entre otros. Aun así, se encontró una gran cantidad de artículos que utilizaban directamente modelos SIR y SEIR sin ningún tipo de modificación, haciendo una simplificación desmedida del fenómeno de transmisión del COVID-19. Asimismo, se identificaron algunas problemáticas a la hora de implementar los modelos matemáticos: la presencia y calidad de los datos de casos diarios en algunos países afectados. Finalmente, se sugiere que los modelos matemáticos estén en constante actualización junto a la publicación de las investigaciones relacionadas con virología y epidemiología de la enfermedad.

19.
J Chem Phys ; 152(8): 084701, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32113360

RESUMO

Density functional theory calculations are reported that elucidate the initial steps toward Au ad-island nucleation on c(2 × 2)-Cl covered Au(001) surfaces, which is relevant for Au electrodeposition in Cl- containing electrolytes. The atomic geometry of (Auad)n adatom structures for n ≤ 4, as well as their stability as a function of Cl chemical potential, has been determined. The electrolyte, however, has not been accounted for in the computation. We find a weakly bonded (AuadCl2)-chain as the most stable structure in the case of Cl chemical potentials such that Cl vacancies are suppressed. In the range of Cl chemical potential, where Cl vacancies occur in equilibrium and bind to an (modified) Auad induced ad-structure, the formation of a dimer from two monomers is accompanied by an energy gain between 0.06 and 0.23 eV. For Auad trimer and tetramer formation, the calculations suggest a similar tendency. This suggests that on c(2 × 2)-Cl covered Au(001) surfaces, the Au ad-island nucleation is supported by the presence of vacancies in the Cl adlayer.

20.
Mem Inst Oswaldo Cruz ; 115: e190357, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130369

RESUMO

BACKGROUND: Viruses can modulate intracellular signalling pathways to complete their infectious cycle. Among these, the PI3K/Akt pathway allows prolonged survival of infected cells that favours viral replication. GSK3ß, a protein kinase downstream of PI3K/Akt, gets inactivated upon activation of the PI3K/Akt pathway, and its association with viral infections has been recently established. In this study, the role of GSK3ß during Dengue virus-2 (DENV-2) infection was investigated. METHODS: GSK3ß participation in the DENV-2 replication process was evaluated with pharmacological and genetic inhibition during early [0-12 h post-infection (hpi)], late (12-24 hpi), and 24 hpi in Huh7 and Vero cells. We assessed the viral and cellular processes by calculating the viral titre in the supernatants, In-Cell Western, western blotting and fluorescence microscopy. RESULTS: Phosphorylation of GSK3ß-Ser9 was observed at the early stages of infection; neither did treatment with small molecule inhibitors nor pre-treatment prior to viral infection of GSK3ß reduce viral titres of the supernatant at these time points. However, a decrease in viral titres was observed in cells infected and treated with the inhibitors much later during viral infection. Consistently, the infected cells at this stage displayed plasma membrane damage. Nonetheless, these effects were not elicited with the use of genetic inhibitors of GSK3ß. CONCLUSIONS: The results suggest that GSK3ß participates at the late stages of the DENV replication cycle, where viral activation may promote apoptosis and release of viral particles.


Assuntos
Vírus da Dengue/enzimologia , Quinases da Glicogênio Sintase/antagonistas & inibidores , Quinases da Glicogênio Sintase/fisiologia , Replicação Viral/fisiologia , Aedes/citologia , Animais , Apoptose/fisiologia , Western Blotting , Linhagem Celular Tumoral , Microscopia de Fluorescência , Fosforilação/fisiologia , Transdução de Sinais
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