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1.
Expert Rev Anti Infect Ther ; : 1-11, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33522327

RESUMO

INTRODUCTION: Disease outbreaks of acquired immunodeficiency syndrome, severe acute respiratory syndrome, pandemic H1N1, H7N9, H5N1, Ebola, Zika, Middle East respiratory syndrome, and recently COVID-19 have raised the attention of the public over the past half-century. Revealing the characteristics and epidemic trends are important parts of disease control. The biological scenarios including transmission characteristics can be constructed and translated into mathematical models, which can help to predict and gain a deeper understanding of diseases. AREAS COVERED: This review discusses the models for infectious diseases and highlights their values in the field of public health. This information will be of interest to mathematicians and clinicians, and make a significant contribution toward the development of more specific and effective models. Literature searches were performed using the online database of PubMed (inception to August 2020). EXPERT OPINION: Modeling could contribute to infectious disease control by means of predicting the scales of disease epidemics, indicating the characteristics of disease transmission, evaluating the effectiveness of interventions or policies, and warning or forecasting during the pre-outbreak of diseases. With the development of theories and the ability of calculations, infectious disease modeling would play a much more important role in disease prevention and control of public health.

2.
Nat Prod Res ; : 1-6, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33624565

RESUMO

Toona sinensis is a medicinal and edible plant that belongs to the genus Toona of family Meliaceae. Phytochemical investigations carried out on this plant, seven apotirucallane-type triterpenoids (1-7), two cycloartane-type triterpenoids (8-9), four sterols (10-13), two sesquiterpenes (14-15), four phenols (16-19), and one lignin (20) were isolated from the pericarp of T. sinensis by silica gel column and preparative middle pressure liquid chromatography. Their structures were identified by interpretation of NMR and comparison with those reported in the literature. Compounds 11-12, 15-16, and 18 were isolated from the family Meliaceae, compounds 13-14 were obtained from the genus Toona, and compound 19 was obtained from T. sinensis for the first time. Additionally, the cytotoxicity and polyol pathway (PP) inhibitory activities of active constituents were evaluated in rat glomerular mesangial cells cultured under high glucose conditions, suggesting their potential application for a PP inhibitor.

3.
Int J Epidemiol ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33517415

RESUMO

BACKGROUND: Although female sex workers (FSWs) have long been identified as a key human papillomavirus (HPV)-affected population, the burden and scope of their disproportionate risk for HPV infection have not been systematically estimated. We therefore aimed to estimate the prevalence of HPV and the distribution of HPV types in FSWs at the country, regional and global levels. METHODS: We searched the PubMed, Embase, SCOPUS, EBSCO, ProQuest, Cochrane Library and Web of Science databases for articles published between 1 January 1990 and 31 June 2019. Studies of genital HPV prevalence in FSWs, or with sufficient data (e.g. adequate number of HPV-positive cases and sample size) to compute prevalence rates in FSWs, were included in this systematic review. The meta-analysis was completed using the random effects model. RESULTS: We ultimately identified 107 studies in 45 countries or regions with sufficient data to calculate HPV prevalence in FSWs. The pooled global HPV prevalence among FSWs was 39.5% (95% CI 35.3, 43.9%), with notable variations by WHO region and country. Globally, the five most common HPV types in FSWs were HPV16 (9.0%), HPV 52 (8.3%), HPV89 (7.0%), HPV58 (6.2%), and HPV53 (5.3%). CONCLUSIONS: Our findings suggest that FSWs are disproportionately affected by HPV, which is more pronounced in the Western Pacific and African regions, and are therefore in need of prevention, treatment and care services.

4.
Int J Infect Dis ; 104: 458-464, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33444755

RESUMO

OBJECTIVES: The role of asymptomatic infections in the transmission of COVID-19 have drawn considerable attention. Here, we performed a meta-analysis to summarize the epidemiological and radiographical characteristics of asymptomatic infections associated with COVID-19. METHODS: Data on the epidemiological and radiographical characteristics of asymptomatic infections were extracted from the existing literature. Pooled proportions with 95% confidence intervals were then calculated using a random effects model. RESULTS: A total of 104 studies involving 20,152 cases were included. The proportion of asymptomatic individuals among those with COVID-19 was 13.34% (10.86%-16.29%), among which presymptomatic and covert infections accounted for 7.64% (4.02%-14.04%) and 8.44% (5.12%-13.62%), respectively. The proportions of asymptomatic infections among infected children and healthcare workers were 32.24% (23.08%-42.13%) and 36.96% (18.51%-60.21%), respectively. The proportion of asymptomatic infections was significantly higher after 2020/02/29 than before (33.53% vs 10.19%) and in non-Asian regions than in Asia (28.76% vs 11.54%). The median viral shedding duration of asymptomatic infections was 14.14 days (11.25-17.04). A total of 47.62% (31.13%-72.87%) of asymptomatic infections showed lung abnormalities, especially ground-glass opacity (41.11% 19.7%-85.79%). CONCLUSIONS: Asymptomatic infections were more commonly found in infected children and healthcare workers and increased after 2020/02/29 and in non-Asian regions. Chest radiographical imaging could be conducive to the early identification of asymptomatic infections.

5.
Ecotoxicol Environ Saf ; 211: 111896, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33440267

RESUMO

Maduramicin, an extensively used anticoccidial drug, has been introduced into environment due to poorly absorbed in the intestine of broiler chicken. To understand the potential ecological toxicity of maduramicin on aquatic organisms, acute and subacute toxicity, hemolymph biochemistry, histopathology and the expressions of drug metabolism and stress response genes of crayfish (Procambius clarkii) were investigated in this study. For the first time, the 96 h median lethal concentration (LC50) of maduramicin on crayfish was 67.03 mgL-1 with a 95% confidence interval (54.06-81.32 mgL-1). Then, the crayfish were exposed to 0.7 mgL-1 (1/100 LC50), 3.5 mgL-1 (1/20 LC50) and 7.0 mgL-1 (1/10 LC50) maduramicin for 28 days. Maduramicin significantly altered biochemical parameters including AST, ALT, CK, LDH and ALP of hemolymph in crayfish at several time points. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) of crayfish gills, hepatopancreas and abdominal muscle were significantly decreased or elevated by different concentrations of maduramicin treatment at varying time points. Furthermore, histopathological damage of crayfish gills, hepatopancreas and abdominal muscle were observed in a concentration-dependent manner. The expressions of metabolic and stress response genes (CYP450, GST, COX1, COX2, HSP70 and MT) in hepatopancreas of crayfish were significantly up-regulated by maduramicin (7.0 mgL-1) treatment for 8 h to 7 d, and returned to normal levels after the removal of maduramicin for 3-7 days. In conclusion, our findings demonstrated that environmental exposure of maduramicin threaten to the health of crayfish living in the areas nearby livestock farms or pharmaceutical factory. Crayfish exhibited resistance to the stress of maduramicin via activating drug metabolite and detoxification pathways.


Assuntos
Antibacterianos/toxicidade , Astacoidea/fisiologia , Lactonas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Organismos Aquáticos/metabolismo , Astacoidea/efeitos dos fármacos , Catalase/metabolismo , Brânquias/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Hemolinfa/metabolismo , Hepatopâncreas/efeitos dos fármacos , Inativação Metabólica , Estresse Oxidativo/efeitos dos fármacos , Alimentos Marinhos , Superóxido Dismutase/metabolismo
6.
Food Chem ; 338: 127991, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32950867

RESUMO

Photoperiod and temperature are vital environmental factors that regulate plant developmental processes. However, the roles of these factors in garlic bulb enlargement are unclear. In this report, responses of garlic bulb morphology and physiology to combinations of photoperiod (light/dark: 10/14 h, 12/12 h, 14/10 h) and temperature (light/dark: 25/18 °C, 30/20 °C) were investigated. For garlic cultivar G103, bulb characteristics, phytohormones (IAA, ABA, ZT, tZR, JA), allicin and phenolic acids (p-coumaric and p-hydroxybenzoic) were highest under a photoperiod of 14 h at 30 °C. Maximum GA was observed under 14 h + 30 °C for cv. G2011-5. Maximum caffeic, ferulic and vanillic acids were detected for cv. G2011-5 at 14 h + 30 °C, 12 h + 25 °C and 14 h + 25 °C, respectively. Flavonoids (myricetin, quercetin, kaempferol and apigenin) were not detected in this trial. This is the first report describing the impact of long periods of light duration and higher temperatures on garlic morphology, phytohormones, phenolic acids and allicin content.


Assuntos
Alho/crescimento & desenvolvimento , Alho/efeitos da radiação , Fotoperíodo , Caules de Planta/crescimento & desenvolvimento , Caules de Planta/efeitos da radiação , Temperatura , Caules de Planta/química
7.
Virus Res ; 291: 198186, 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33075446

RESUMO

Characterization of host adaptation markers among human isolates is important for recognizing the potential for cross-species transmission in avian influenza A viruses. Here, we studied two new potential adaptive mutations, V292I and D740A, in the PB2 protein that were identified by a multi-factor regression model. The study shows that the prevalence of the PB2-V292I mutation is increased in H7N9 influenza viruses isolated from both humans and birds over the past 6 years. The phylogenetic tree showed that influenza A/H7N9 has a lineage based on the strains containing PB2-292I. Polymerase complexes containing PB2-292I/627K derived from H7N9 exhibit increased polymerase activity. PB2-292I coupled with 627K also enhances viral transcription and replication in cells, whereas PB2-292I alone did not show the same effect in the H7N9 virus. However, PB2-740A only had a limited prevalence in 2013, and the change from D to A in PB2-740A may have a negative effect on the replication of the H7N9 virus in cells.

8.
Clin Rehabil ; : 269215520970737, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33222527

RESUMO

OBJECTIVE: To determine the effectiveness of proprioceptive training on knee function and proprioception following anterior cruciate ligament reconstruction. DATA SOURCES: PubMed, EMBASE, The Cochrane Library, Ovid, EBMSCO-host, ScienceDirect, CNKI, VIP, WanFang Data and CBM were searched until 2nd October 2020. REVIEW METHODS: Trials with proprioceptive training for patients with anterior cruciate ligament reconstruction were included. Study screening, data extraction, risk of bias and quality assessments were performed independently by two researchers. We performed a stratified analysis based on the quality of the study. Sensitivity analyses were performed if the heterogeneity was high. RESULTS: Seventeen trials with 878 participants were included, and 12/17 with low quality. After stratified analysis, the pooled effect of high-quality studies showed significant improvement for proprioceptive training group in range of motion (P < 0.05, I2 = 0%), but no differences in Cincinnati knee rating system score (P > 0.05, I2 = 83%), hop test (P>0.05, I2 = 0%) and proprioception (P = 0.17, I2 = 77%) compared to conventional training group; while the pooled effect of low-quality studies showed significant differences in knee functional improvement (P < 0.00001, I2 = 69%), but no difference in proprioception (P > 0.05, I2 = 84%) between two groups. The pooled effect of all studies showed a significant benefit in both function and proprioception. CONCLUSION: The effects of proprioceptive training on knee functional and proprioceptive improvement after anterior cruciate ligament reconstruction is mixed. It is more likely that proprioceptive training in high-quality studies has few detectable effects and that low-quality studies show an effect because of an unconscious bias. A large well designed high-quality study needs to be undertaken in the future.

9.
Int J Biol Macromol ; 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33137382

RESUMO

Secretion-associated and ras-related protein 1 (Sar1) is a small GTPase that plays an important role in the transport of protein coated with coat protein complex II vesicles. However, its alternative roles in the biological processes of Procambarus clarkii remain unclear. Here, a sar1 gene (named as Pc-sar1) with an open reading frame of 582 bp from P. clarkii was identified. Pc-sar1 was expressed in all examined tissues with highest expression levels in muscle, which was determined by real-time PCR and western blotting. After the induction of lipopolysaccharide (LPS) and polycytidylic acid (Poly I: C), the transcriptional levels of Pc-sar1 differed in hepatopancreas, gill, muscle and intestine. In contrast, the expression of Pc-sar1 was upregulated by 20-hydroxyecdysone in these four tissues. In addition, the RNA interference of Pc-sar1 significantly affected the expression levels of immune and hormone-related genes. These results indicate that Pc-sar1 is involved in the innate immune response and ecdysteroid signaling pathway.

10.
BMC Plant Biol ; 20(1): 501, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33143654

RESUMO

BACKGROUND: Nitrogen (N) deficiency is a major constraint for plant production in many areas. Developing the new crop genotypes with high productivity under N deficiency is an important approach to maintain agricultural production. Therefore, understanding how plant response to N deficiency and the mechanism of N-deficiency tolerance are very important for sustainable development of modern crop production. RESULTS: In this study, the physiological responses and fatty acid composition were investigated in 24 wheat cultivars under N-deficient stress. Through Pearson's correlation analysis and principal component analysis, the responses of 24 wheat cultivars were evaluated. The results showed that the plant growth and carbohydrate metabolism were all differently affected by N deficiency in all tested wheat cultivars. The seedlings that had high shoot biomass also maintained high level of chlorophyll content under N deficiency. Moreover, the changes in fatty acid composition, especially the linolenic acid (18:3) and the double bond index (DBI), showed close positive correlations with the shoot dry weight and chlorophyll content alterations in response to N-deficient condition. These results indicated that beside the chlorophyll content, the linolenic acid content and DBI may also contribute to N-deficiency adaptation, thus could be considered as efficient indicators for evaluation of different response in wheat seedlings under N-deficient condition. CONCLUSIONS: The alteration in fatty acid composition can potentially contribute to N-deficiency tolerance in plants, and the regulation of fatty acid compositions maybe an effective strategy for plants to adapt to N-deficient stress.

11.
Front Microbiol ; 11: 585194, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193231

RESUMO

Tembusu virus (TMUV) is a mosquito-borne flavivirus that most commonly affects adult breeder and layer ducks. However, a TMUV-caused neurological disease has also been found in ducklings below 7 weeks of age, highlighting the need to develop a safe vaccine for young ducklings. In this study, a plaque-purified PS TMUV strain was attenuated by serial passage in BHK-21 cells. Using 1-day-old Pekin ducklings as a model, the virus was confirmed to be attenuated sufficiently after 180 passages, whereas the neutralizing antibody response elicited by the 180th passage virus (PS180) was substantially impaired compared with PS. The findings suggest that sufficient attenuation results in loss of immunogenicity in the development of the live-attenuated TMUV vaccine. Comparative sequence analysis revealed that PS180 acquired one mutation (V41M) in prM and four mutations (T70A, Y176H, K313R, and F408L) in the envelope (E) protein. To identify the amino acid substitution(s) associated with loss of immunogenicity of PS180, we rescued parental viruses, rPS and rPS180, and produced mutant viruses, rPS180-M41V, rPS180-A70T, rPS180-H176Y, rPS180-R313K, rPS180-L408F, and rPS180-M5, which contained residue 41V in prM, residues 70T, 176Y, 313K, and 408F in E, and combination of the five residues, respectively, of PS in the backbone of the rPS180 genome. The neutralizing antibody response elicited by rPS180-L408F and rPS180-M5 was significantly higher than those by other mutant viruses and comparable to that by rPS. Furthermore, we produced mutant virus rPS-F408L, which contained residue 408L of PS180 in the backbone of the rPS genome. The F408L mutation conferred significantly decreased neutralizing antibody response to rPS-F408L, which was comparable to that elicited by rPS180. Based on homologous modeling, residue 408 was predicted to be located within the first helical domain of the stem region of the E protein (EH1). Together, these data demonstrate that a single mutation within the EH1 domain exerts a dramatical impact on the TMUV neutralizing antibody response. The present work may enhance our understanding of molecular basis of the TMUV neutralizing antibody response, and provides an important step for the development of a safe and efficient live-attenuated TMUV vaccine.

12.
Infect Dis Ther ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146854

RESUMO

INTRODUCTION: Sepsis is a complication in acute-on-chronic liver failure (ACLF) patients associated with high rates of mortality and morbidity. Early diagnosis of sepsis in ACLF patients can improve prognosis. This study aimed to explore potential effective biomarkers for the early diagnosis of sepsis in ACLF patients. METHODS: Ninety-four ACLF patients with sepsis were enrolled from 10 hospitals across China from January 2015 to June 2016 as well as 49 ACLF patients without infection from Xiangya Hospital. The first-day admission data and SOFA score and CLIF-SOFA score were collected. The differences of indicators between groups were compared with Kruskal-Wallis test. The receiver-operating characteristic (ROC) curve was analyzed to evaluate the diagnostic efficiency of the selected factors. RESULTS: Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) and presepsin were significantly higher in ACLF-sepsis patients compared with ACLF patients with no infection (P < 0.001). sTREM-1 and presepsin presented higher diagnostic value in sepsis for ACLF patients compared with other biomarkers [white blood cells (WBC), procalcitonin (PCT) and C-reactive protein (CRP)]. Combining sTREM-1 or presepsin with the CLIF-SOFA score increased the diagnostic efficiency (AUC = 0.876 or AUC = 0.913, respectively). CONCLUSIONS: sTREM-1 and presepsin are potential biomarkers for the early diagnosis of sepsis in ACLF patients. The combination of presepsin and the CLIF-SOFA score is a promising method for diagnosing sepsis in ACLF patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02457637.

13.
Sci China Life Sci ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33165811

RESUMO

Despite the use of many types of chemotherapies for pancreatic cancer, optimal efficacy has not been obtained so far. Pancreatic cancer shows a high incidence of TP53 mutations, inactivating its tumor suppressor activity. In this study, we identified sodium cantharidinate as a novel, potential anti-pancreatic cancer agent that activates p53 function. Sodium cantharidinate reduced the viability of pancreatic cancer cells, including the human primary pancreatic cancer cells, PANC-1, AsPC-1, SW1990 and BXPC-3, in a dose-dependent manner. Sodium cantharidinate induced apoptosis and DNA damage of pancreatic cancer cells. Furthermore, proteome-wide sequencing analysis detected a marked perturbation in p53 signaling pathway on PANC-1 cells upon sodium cantharidinate. Consistent with the previous results, sodium cantharidinate treatment decreased Bcl-2 and mitochondrial cytochrome-c protein expression, as well as phosphorylation of MDM2; meanwhile, it increased the levels of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP, Bax, and phosphorylated p53, thus inducing the apoptosis of pancreatic cancer cells. The p53-activating effect of sodium cantharidinate was strongly abrogated by treatment with TP53-targeting shRNA. Moreover, sodium cantharidinate inhibited neoplasm growth via the JAK2-STAT3 pathway, which was inhibited by shRNA-TP53 and triggered by combination with gemcitabine. Combination therapy indicated that sodium cantharidinate and gemcitabine synergistically reduced ex vivo and in vivo growth of pancreatic neoplasm. Further docking studies revealed the different binding fates of sodium cantharidinate to activate wild-type p53 function. Thus, sodium cantharidinate could be a potential agent with promising anti-pancreatic cancer efficacy.

14.
Sensors (Basel) ; 20(20)2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33053662

RESUMO

The dynamic response of a polyvinylidene fluoride (PVDF) cantilever beam under excitation of water droplet impact is investigated by developing an electromechanical model. In the model, the governing equations of beam motion and output voltage are derived in the theoretical way, such that the voltage across the PVDF layer and the cantilever deflection can be predicted. The motion of the beam is described by the multi-mode vibration model through which more accurate results can be obtained. The predicted results of the model are validated by the experiment. Combined with the experiment and the model, the effect of surface wettability on droplet-substrate interaction mechanisms is investigated, which provides an insight into the improvement of mechanical-to-electrical energy conversion efficiency in raindrop energy harvesting (REH) applications. Results show: (1) the droplet splash on a super-hydrophobic beam surface has a positive effect on voltage generation. The splash limit that affects the reaction force of the impacting droplet is experimentally determined and greatly dominant by the Weber number. (2) Small-scaled droplets in splash regime allow generating higher voltage output from a super-hydrophobic beam surface than from an untreated hydrophilic beam surface. (3) Tests of successive droplet impacts also show that a super-hydrophobic surface performs better over a hydrophilic surface by producing constant peak voltage and higher electrical energy harvested. In this case, the voltage measured from the hydrophilic surface decreases gradually as the water layer is accumulated. Overall, the electromechanical behaviors of a super-hydrophobic PVDF cantilever sensor can be well predicted by the model which shows a great potential in energy harvesting by maximizing the inelastic collision upon droplet-substrate interactions.

15.
CMAJ Open ; 8(4): E619-E626, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33037069

RESUMO

BACKGROUND: In studies showing associations between ambient air pollution and myocardial infarction (MI), data have been lacking on the inherent spatial variability of air pollution. The aim of this study was to determine whether the long-term spatial distribution of air pollution influences short-term temporal associations between air pollution and admission to hospital for MI. METHODS: We identified adults living in Calgary who were admitted to hospital for an MI between 2004 and 2012. We evaluated associations between short-term exposure to air pollution (ozone [O3], nitrogen dioxide [NO2], sulfur dioxide [SO2], carbon monoxide [CO], particulate matter < 10 µm in diameter [PM10] and particulate matter < 2.5 µm in diameter [PM2.5]), and hospital admissions for MI using a time-stratified, case-crossover study design. Air Quality Health Index (AQHI) scores were calculated from a composition of O3, NO2 and PM2.5. Conditional logistic regression models were stratified by low, medium and high levels of neighbourhood NO2 concentrations derived from land use regression models; results of these analyses are presented as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: From 2004 to 2012, 6142 MIs were recorded in Calgary. Individuals living in neighbourhoods with higher long-term air pollution concentrations were more likely to be admitted to hospital for MI after short-term elevations in air pollution (e.g., 5-day average NO2: OR 1.20, 95% CI 1.03-1.40, per interquartile range [IQR]) as compared with regions with lower air pollution (e.g., 5-day average NO2: OR 0.90, 95% CI 0.78-1.04, per IQR). In high NO2 tertiles, the AQHI score was associated with MI (e.g., 5-day average OR 1.13, 95% CI 1.02-1.24, per IQR; 3-day average OR 1.13, 95% CI 1.04-1.23, per IQR). INTERPRETATION: Our results show that the effect of air pollution on hospital admissions for MI was stronger in areas with higher NO2 concentrations than that in areas with lower NO2 concentrations. Individuals living in neighbourhoods with higher traffic-related pollution should be advised of the health risks and be attentive to special air quality warnings.

16.
BMC Public Health ; 20(1): 1551, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059639

RESUMO

BACKGROUND: Knowledge of geospatial pattern in comorbidities prevalence is critical to an understanding of the local health needs among people with osteoarthritis (OA). It provides valuable information for targeting optimal OA treatment and management at the local level. However, there is, at present, limited evidence about the geospatial pattern of comorbidity prevalence in Alberta, Canada. METHODS: Five administrative health datasets were linked to identify OA cases and comorbidities using validated case definitions. We explored the geospatial pattern in comorbidity prevalence at two standard geographic areas levels defined by the Alberta Health Services: descriptive analysis at rural-urban continuum level; spatial analysis (global Moran's I, hot spot analysis, cluster and outlier analysis) at the local geographic area (LGA) level. We compared area-level indicators in comorbidities hotspots to those in the rest of Alberta (non-hotspots). RESULTS: Among 359,638 OA cases in 2013, approximately 60% of people resided in Metro and Urban areas, compared to 2% in Rural Remote areas. All comorbidity groups exhibited statistically significant spatial autocorrelation (hypertension: Moran's I index 0.24, z score 4.61). Comorbidity hotspots, except depression, were located primarily in Rural and Rural Remote areas. Depression was more prevalent in Metro (Edmonton-Abbottsfield: 194 cases per 1000 population, 95%CI 192-195) and Urban LGAs (Lethbridge-North: 169, 95%CI 168-171) compared to Rural areas (Fox Creek: 65, 95%CI 63-68). Comorbidities hotspots included a higher percentage of First Nations or Inuit people. People with OA living in hotspots had lower socioeconomic status and less access to care compared to non-hotspots. CONCLUSIONS: The findings highlight notable rural-urban disparities in comorbidities prevalence among people with OA in Alberta, Canada. Our study provides valuable evidence for policy and decision makers to design programs that ensure patients with OA receive optimal health management tailored to their local needs and a reduction in current OA health disparities.

17.
Nat Commun ; 11(1): 5210, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060578

RESUMO

Human insulinomas are rare, benign, slowly proliferating, insulin-producing beta cell tumors that provide a molecular "recipe" or "roadmap" for pathways that control human beta cell regeneration. An earlier study revealed abnormal methylation in the imprinted p15.5-p15.4 region of chromosome 11, known to be abnormally methylated in another disorder of expanded beta cell mass and function: the focal variant of congenital hyperinsulinism. Here, we compare deep DNA methylome sequencing on 19 human insulinomas, and five sets of normal beta cells. We find a remarkably consistent, abnormal methylation pattern in insulinomas. The findings suggest that abnormal insulin (INS) promoter methylation and altered transcription factor expression create alternative drivers of INS expression, replacing canonical PDX1-driven beta cell specification with a pathological, looping, distal enhancer-based form of transcriptional regulation. Finally, NFaT transcription factors, rather than the canonical PDX1 enhancer complex, are predicted to drive INS transactivation.


Assuntos
Regulação Neoplásica da Expressão Gênica , Insulina/genética , Insulina/metabolismo , Insulinoma/genética , Insulinoma/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Adulto , Idoso , Sítios de Ligação , Biologia Computacional , Metilação de DNA , Feminino , Proteínas de Homeodomínio/metabolismo , Humanos , Células Secretoras de Insulina/metabolismo , Masculino , Doenças Metabólicas/genética , Doenças Metabólicas/metabolismo , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Transativadores/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Adulto Jovem
18.
Nucleic Acids Res ; 48(19): 11054-11067, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33045733

RESUMO

The two-gene module HEPN/MNT is predicted to be the most abundant toxin/antitoxin (TA) system in prokaryotes. However, its physiological function and neutralization mechanism remains obscure. Here, we discovered that the MntA antitoxin (MNT-domain protein) acts as an adenylyltransferase and chemically modifies the HepT toxin (HEPN-domain protein) to block its toxicity as an RNase. Biochemical and structural studies revealed that MntA mediates the transfer of three AMPs to a tyrosine residue next to the RNase domain of HepT in Shewanella oneidensis. Furthermore, in vitro enzymatic assays showed that the three AMPs are transferred to HepT by MntA consecutively with ATP serving as the substrate, and this polyadenylylation is crucial for reducing HepT toxicity. Additionally, the GSX10DXD motif, which is conserved among MntA proteins, is the key active motif for polyadenylylating and neutralizing HepT. Thus, HepT/MntA represents a new type of TA system, and the polyadenylylation-dependent TA neutralization mechanism is prevalent in bacteria and archaea.


Assuntos
Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/metabolismo , Shewanella/metabolismo , Sistemas Toxina-Antitoxina
19.
J Fish Biol ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33000466

RESUMO

Selenium, as an essential trace element, interferes through selenoproteins in many physiological processes of plants and mammals. Its antiviral activity has recently attracted much attention because selenium improves the antiviral capacity of animal cells against a few viruses relevant to human diseases. In this study, the red elemental selenium was purified from the fermentative culture of Herbaspirillum camelliae WT00C and then used to culture epithelioma papulosum cyprinid (EPC) cells or feed crucian carp and zebrafish. Finally, its antiviral effects were investigated at the cell level and living fishes after spring viraemia of carp virus infection. At the cell level, 5, 10 and 20 µg ml-1 red elemental selenium significantly induced the expression of interferon (IFN) and ISG15 genes in EPC cells. The viral TCID50 (50% tissue culture infective dose) values in the EPC cells incubated with 5, 10 and 20 µg ml-1 red elemental selenium were significantly less than those of the control. More expression of IFN and ISG15 genes and less TCID50 values indicate that red elemental selenium indeed improves the antiviral capability of EPC cells. In the crucian carp fed with the food containing 5 and 10 µg g-1 red elemental selenium, IFN expressions showed 13- and 39-fold increases at the 16th day of post-injection, and its expression was dependent on selenium concentrations. Meanwhile, no fish death occurred in all the experimental groups. In the zebrafish fed with the red worm containing 5 µg g-1 red elemental selenium, IFN and Mx expressions and survival rate were significantly higher than those of the control. The results of this study show that red elemental selenium indeed improves the antiviral activity of fish. The antiviral effects of selenium mainly come from its immune regulation through its incorporation into selenoproteins. The optimum level of selenium contributes to improving fish immunity, whereas excess selenium causes excessive immune and inflammatory responses.

20.
Biochem Pharmacol ; : 114285, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33069665

RESUMO

Multi-gene prognostic signatures of long non-coding RNAs (lncRNAs) provide new insights into mechanisms of HER2-negative breast cancer development and progression, and predict distant relapse-free survival (DRFS) of patients receiving taxane and anthracycline-based neoadjuvant chemotherapy. The aim of this study was to develop such a multi-lncRNAs signature. Optimal multiple candidate signature lncRNAs associated with DRFS were firstly identified by a univariate Cox proportional hazard regression survival analysis and a robust likelihood-based survival analysis of the GEO dataset GSE25055. A nine-lncRNA prognostic risk score model Risk Score = 0.0289 × EXPLOC100507388 - 0.0814 × EXPLINC00094 - 0.2422 × EXPSMG7-AS1 - 0.2433 × EXPPP14571 + 0.4690 × EXPASAP1-IT1 - 0.2483 × EXPLOC103344931 - 0.2464 × EXPFAM182A + 0.3349 × EXPHCG26 - 0.0216 × EXPLINC00963 was built according to the coefficients of multivariate survival analysis of the association between the candidate lncRNAs and survival. EXPlncRNA was the standardized log2-transformed expression level of the gene. According to this model, higher scores predicted lower survival probability. The area under Receiver operating characteristic (ROC) curve (AUC) was 0.777 to 0.823 from 1- to 7- year survival rate. The model and its individual lncRNAs differentiated survival probability between the higher scores (expression) and the lower scores (expression). The nine-lncRNA signature had the robust prognostic power compared with ER, PR, tumor size (T), lymph node invasion (N), TNM stage, pathologic response, chemosensitivity prediction and PAM50 signature. These results were consistent with those based on the GEO dataset GSE25065. The predictive nomograms integrating both the nine-lncRNA signature classifier and clinical-pathological risk factors were robust in predicting 1-, 3- and 5- year survival probabilities. These results supported that the nine-lncRNA signature was a robust and effective model in predicting DRFS of patients with HER2-negative breast cancer following taxane and anthracycline-based neoadjuvant chemotherapy.

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