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1.
Braz. j. biol ; 84: e250607, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1355881

RESUMO

Abstract Newcastle disease (ND) is an infectious, highly contagious and lethal disease of avian species. It is considered that ducks are natural reservoir or carrier for Newcastle disease virus (NDV) and are resistant against different strains of NDV. Current study was designed to evaluate the pathogenesis of Newcastle disease in domestic ducks through histopathology, immunohistochemistry (IHC) and serum biochemical changes. For this purpose, eighty ducks were reared for 42 days and divided in two groups A and B. Ducks in group A were challenged with (NDV) at rate of 0.1 ml of ELD50 (virus titer 107.32/100µl) on second week of age, whereas Group B was control negative. Splenomegaly, atrophy of thymus and necrotic lesion in kidney were observed on 9th day of post infection. Hepatic degeneration and mononuclear cell infiltration were noticed in proventriculus and intestine in challenged ducks. Viral antigen detected in lungs, intestine, proventriculus and lymphoid organs of infected ducks through IHC. Albumin and total protein values were significantly low in infected groups A as compared to control group B. ALT, AST, and ALP values were significantly high in infected group A. On 5th and 7th day of post infection oropharyngeal swabs were negative for NDV and cloacal swabs were positive for NDV through Reverse transcriptase polymerase chain reaction. It is concluded that ducks are susceptible to NDV and virulent strain of NDV caused disease in ducks.


Resumo A doença de Newcastle (DN) é uma doença infecciosa, altamente contagiosa e letal de espécies aviárias. Considera-se que os patos são reservatórios ou portadores naturais do vírus da doença de Newcastle (VDN) e são resistentes a diferentes cepas de VDN. O presente estudo foi desenvolvido para avaliar a patogênese da DN em patos domésticos por meio de histopatologia, imuno-histoquímica (IHQ) e alterações bioquímicas séricas. Para este propósito, 80 patos foram criados por 42 dias e divididos em dois grupos A e B. Os patos do grupo A foram submetidos ao VDN a uma taxa de 0,1 ml de ELD50 (título viral de 107,32 / 100 µl) na segunda semana de idade, enquanto o Grupo B foi controle negativo. Esplenomegalia, atrofia do timo e lesão necrótica no rim foram observadas no 9º dia pós-infecção. Degeneração hepática e infiltração de células mononucleares foram observadas no proventrículo e intestino em patos infectados. Antígeno viral foi detectado em pulmões, intestino, proventrículo e órgãos linfoides de patos infectados por IHQ. Os valores de albumina e proteína total foram significativamente baixos no grupo A infectado em comparação com o grupo B. Os valores de ALT, AST e ALP foram significativamente altos no grupo A. No 5º e no 7º dia após a infecção, os esfregaços orofaríngeos foram negativos para VDN, enquanto os esfregaços cloacais foram positivos para VDN por meio da reação em cadeia da polimerase via transcriptase reversa. Conclui-se que os patos são suscetíveis ao VDN e à cepa virulenta de VDN que causou doenças em patos.


Assuntos
Animais , Vírus da Doença de Newcastle , Patos , Doença de Newcastle/diagnóstico
2.
Braz. j. biol ; 84: e256799, 2024. tab, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1360215

RESUMO

Southern corn leaf blight (SCLB) is one of the most important corn leaf diseases. Appropriate management strategies and the use of resistant cultivars allow disease control. Therefore, knowing the aspects related to the pathogen and the response of hosts makes it possible to design efficient strategies for selecting genotypes resistant to this disease. In this sense, the objective was to carry out the Bipolaris maydis isolate characterization, evaluating the pathogenicity in different popcorn lines and the symptoms generated in the host after inoculation. The isolate characterization consisted of the macromorphological evaluation of the colonies and the micromorphological evaluation of the conidia in the PDA medium. An experiment was carried out in a greenhouse to evaluate the pathogenicity of the isolate, using 20 inbred lines of popcorn in a randomized block design with four replicates. Inoculation was carried out by spraying leaves, with a suspension containing 1.0 x 104 conidia.ml-1 of the CF/UENF 501 isolate of B. maydis. An incidence assessment and three assessments of disease symptom severity were performed, with seven days intervals between evaluations. The morphological characterization data of the isolate were analyzed using descriptive statistics, and for disease severity, the linear regression model was applied the first-degree model. The variance analysis was performed for the linear and angular coefficients obtained for each treatment. When a difference was found, the Scott-Knott clustering algorithm at 5% significance was applied. The isolate had gray-green colonies, a cottony appearance, and an irregular shape. The lines L353, L354, and L624 show more resistance at the beginning and throughout the evaluations. The high virulence of the CF/UENF 501 isolate made it possible to differentiate the lines in terms of disease intensity and the pattern of symptoms presented.


Mancha-de-Bipolaris é uma das mais importantes doenças foliares do milho. Estratégias de manejo adequadas e o uso de cultivar resistente permitem o controle da doença, mas para tanto, conhecer os aspectos associados ao patógeno e a resposta do hospedeiro é necessário para traçar estratégias eficientes para seleção de genótipos resistentes a essa doença. Neste sentido, objetivou-se realizar a caracterização do isolado de Bipolaris maydis avaliando a patogenicidade em diferentes linhagens de milho-pipoca e os sintomas gerados no hospedeiro a partir da inoculação. A caracterização do isolado consistiu na avaliação macromorfológica das colônias e micromofológica dos conídios em meio nutritivo BDA. Para avaliação da patogenicidade do isolado foi conduzido um experimento em casa de vegetação utilizando 20 linhagens endogâmicas de milho-pipoca, com delineamento em blocos casualizados, com quatro repetições. A inoculação foi realizada por meio de pulverização em folhas, com uma suspensão contendo 1,0 x 104 conídios.ml-1 do isolado CF/UENF 501 de B. maydis. Foi realizada uma avaliação de incidência e três avaliações de severidade dos sintomas da doença, com o intervalo de sete dias para cada avaliação. Os dados da caracterização morfológica do isolado foram analisados por meio da estatística descritiva e para severidade da doença foi aplicado o modelo de regressão linear de primeiro grau. Realizou-se a análise de variância para o coeficiente linear e angular obtido para cada tratamento e quando constatada diferença aplicou-se o agrupamento de médias de Scott-knott a 5% de significância. O isolado apresentou colônias com coloração cinza esverdeado, aspecto algodonoso e forma irregular. As linhagens L353 e L354 e L624 estão entre as linhagens que apresentaram maior resistência no inicio e ao longo das avaliações. A elevada virulência do isolado CF/UENF 501 possibilitou diferenciar as linhagens quanto a intensidade da doença, bem como o padrão dos sintomas apresentados.


Assuntos
Animais , Controle de Pragas , Zea mays , Genótipo
3.
Braz. j. biol ; 84: e253605, 2024. tab, graf, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1360221

RESUMO

Local and exotic germplasm of tomato remains a major source for genetic improvement. Assessment of such lines for biotic stresses particularly viral diseases are the most important criteria for selection in Pakistan, where Tomato Yellow Leaf Curl Virus (TYLCV) and Tomato Mosaic Virus (ToMV) are the major diseases/viruses. A set of 40 accessions (including indigenous Pakistani lines and exotic germplasm from Europe, the United States, and Asia) were evaluated for their resistance/infection response to ToMV with artificial inoculation under greenhouse conditions. Infection response was quantified through disease scoring and DAS-ELISA test (for ToMV). A subset of 24 lines, was further screened for TYLCV using disease scoring and TAS-ELISA. The tested lines showed significant variability for resistance to ToMV. Only one accession (Acc-17878) was resistant to the ToMV whereas seven accessions i.e. Acc-17890, AVR-261, CLN-312, AVR-321, EUR-333, CLN-352, and CLN-362 expressed resistance to TYLCV. Correlation between phenotypic evaluation was confirmed by the ELISA results in both diseases, although both tools complemented to assess the viral infection status. In future, tomato breeding programs must consider breeding for ToMV and TYLCV resistance (using identified germplasm in our study) so as to deliver virus resistant tomato varieties.


O germoplasma local e exótico do tomate continua sendo uma importante fonte de melhoramento genético. A avaliação de linhagens para estresses bióticos, particularmente as doenças virais, é o critério mais importantes para seleção no Paquistão, onde o vírus da folha amarela do tomate (TYLCV) e o vírus do mosaico do tomateiro (ToMV) são as principais doenças/vírus. Um conjunto de 40 acessos (incluindo linhagens indígenas do Paquistão e germoplasma exótico da Europa, dos Estados Unidos e da Ásia) foi avaliado quanto à resistência/resposta à infecção ao ToMV com inoculação artificial em casa de vegetação. A resposta à infecção foi quantificada por meio de pontuação da doença e de teste DAS-ELISA (para ToMV). Um subconjunto de 24 linhas foi posteriormente rastreado para TYLCV usando pontuação de doença e TAS-ELISA. As linhas testadas apresentaram variabilidade significativa para resistência ao ToMV. Apenas um acesso (Acc-17878) foi resistente ao ToMV, enquanto sete acessos (Acc-17890, AVR-261, CLN-312, AVR-321, EUR-333, CLN-352 e CLN-362) expressaram resistência ao TYLCV. A correlação entre a avaliação fenotípica foi confirmada pelos resultados do ELISA nas duas doenças, embora ambas as ferramentas tenham se complementado para avaliar o estado da infecção viral. No futuro, os programas de melhoramento de tomate devem considerar aperfeiçoamentos para resistência ao ToMV e TYLCV (usando germoplasma identificado em nosso estudo) de modo a fornecer variedades de tomate resistentes a vírus.


Assuntos
Lycopersicon esculentum , Melhoramento Genético , Vírus do Mosaico
4.
BMC Public Health ; 23(1): 207, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721260

RESUMO

BACKGROUND: In China, communicable diseases (CD) have a negative impact on public health and economic stability. The influx of migrants, who make up a substantial portion of China's population and continue to rapidly expand, has seriously hampered CD prevention and control, needing special care. This study aimed to identify key factors influencing the utilization of CD prevention and treatment education (CDPTE) among the floating population. We are confident that the findings will highlight obstacles facing CDPTE among the migrants, and guide future development prevention, treatment of CD, and health education services. METHODS: A sample of migrants aged 15 years and above in 32 provincial units nationwide in 2018 was recruited by stratified multi-stage proportional to population size sampling (PPS). A structured questionnaire survey was conducted via face-to-face interviews. Subsequently, the Anderson health service utilization model was used as the theoretical framework and SPSS 26.0 statistical software was applied to analyze the data. The statistical description of the current situation of CDPTE acceptance and the chi-square test were used to compare the differences in CDPTE acceptance by different characteristics. Multivariate logistic regression was used to analyze key factors affecting the use of CDPTE among migrants. RESULTS: A total of 40.1% of the recruited participants reported receiving education on CD prevention and treatment, primarily delivered through traditional transmission media. Multilevel logistic regression results revealed that male migrants, aged 30-49 years, unmarried, with higher educational attainment, an average monthly household income of CNY 7,500-9,999 (or US$1,176-1,568), working more than 40 h per week, flowing into the Central and Western regions, migrated in the province, self-rated health, contracted family doctors and those with health records were more likely to receive CDPTE (p < 0.05). CONCLUSION: Our findings revealed unsatisfactory acceptance of education on CD prevention and treatment among migrants, implying that health education should be strengthened further. Publicity of relevant policies and works should be strengthened and specific interventions should be developed for key regions as well as vulnerable groups to enhance CDPTE. More financial support should also be provided to improve the quality of health education.


Assuntos
Educação em Saúde , Masculino , Humanos , Estudos Transversais , Escolaridade , China , Densidade Demográfica
5.
Microbiome ; 11(1): 16, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36721270

RESUMO

BACKGROUND: Bacterial viruses, phages, play a key role in nutrient turnover and lysis of bacteria in terrestrial ecosystems. While phages are abundant in soils, their effects on plant pathogens and rhizosphere bacterial communities are poorly understood. Here, we used metagenomics and direct experiments to causally test if differences in rhizosphere phage communities could explain variation in soil suppressiveness and bacterial wilt plant disease outcomes by plant-pathogenic Ralstonia solanacearum bacterium. Specifically, we tested two hypotheses: (1) that healthy plants are associated with stronger top-down pathogen control by R. solanacearum-specific phages (i.e. 'primary phages') and (2) that 'secondary phages' that target pathogen-inhibiting bacteria play a stronger role in diseased plant rhizosphere microbiomes by indirectly 'helping' the pathogen. RESULTS: Using a repeated sampling of tomato rhizosphere soil in the field, we show that healthy plants are associated with distinct phage communities that contain relatively higher abundances of R. solanacearum-specific phages that exert strong top-down pathogen density control. Moreover, 'secondary phages' that targeted pathogen-inhibiting bacteria were more abundant in the diseased plant microbiomes. The roles of R. solanacearum-specific and 'secondary phages' were directly validated in separate greenhouse experiments where we causally show that phages can reduce soil suppressiveness, both directly and indirectly, via top-down control of pathogen densities and by alleviating interference competition between pathogen-inhibiting bacteria and the pathogen. CONCLUSIONS: Together, our findings demonstrate that soil suppressiveness, which is most often attributed to bacteria, could be driven by rhizosphere phage communities that regulate R. solanacearum densities and strength of interference competition with pathogen-suppressing bacteria. Rhizosphere phage communities are hence likely to be important in determining bacterial wilt disease outcomes and soil suppressiveness in agricultural fields. Video Abstract.


Assuntos
Bacteriófagos , Microbiota , Rizosfera , Bactérias/genética , Solo
6.
Adv Kidney Dis Health ; 30(1): 61-68, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36723284

RESUMO

Cardiovascular morbidity and mortality occur with an extraordinarily high incidence in the hemodialysis-dependent end-stage kidney disease population. There is a clear need to improve identification of those individuals at the highest risk of cardiovascular complications in order to better target them for preventative therapies. Twelve-lead electrocardiograms are ubiquitous and use inexpensive technology that can be administered with minimal inconvenience to patients and at a minimal burden to care providers. The embedded waveforms encode significant information on the cardiovascular structure and function that might be unlocked and used to identify at-risk individuals with the use of artificial intelligence techniques like deep learning. In this review, we discuss the experience with deep learning-based analysis of electrocardiograms to identify cardiovascular abnormalities or risk and the potential to extend this to the setting of dialysis-dependent end-stage kidney disease.


Assuntos
Aprendizado Profundo , Falência Renal Crônica , Humanos , Diálise Renal/efeitos adversos , Inteligência Artificial , Falência Renal Crônica/diagnóstico , Eletrocardiografia
7.
Artigo em Alemão | MEDLINE | ID: mdl-36723636

RESUMO

INTRODUCTION: The COVID-19 pandemic is also impacting the medical care for other diseases. The extent to which people with chronic diseases are affected by the suspension of medical services is investigated-differentiating between patient and provider perspectives. METHOD: A cross-sectional study was conducted based on data from the longitudinal Hamburg City Health Study (HCHS). The study population was all HCHS participants (a sample of the population of Hamburg, 45-74 years) between April 2020 and November 2021. Utilisation of medical services was collected via the "COVID-19-module" of the HCHS. The chronic conditions included cardiovascular disease, kidney and lung disease, cancer and diabetes mellitus; analyses were descriptive and multivariate. RESULTS: Of the 2047 participants, 47.9% had at least one previous illness. Of those with pre-existing conditions, 21.4% had at least one healthcare service suspended or an appointment cancelled. In addition, 15.4% stated that they decided by themselves not to attend a doctor's appointment. Specialist care services (43.8% of all cancellations) were cancelled more frequently than general practitioner care (16.6%). After adjustment for age, gender and education, lung disease (OR 1.80; p < 0.008) and cancer (OR 2.33; p < 0.001) were found to be independent risk factors for appointment cancellations by healthcare providers. Of cancellations by patients, 42.2% were due to their fear of an infection with the coronavirus SARS-CoV­2. DISCUSSION: Health policy and the media are faced with the challenge of dealing with fears of infection in the population in such a way that they do not lead to an avoidance of necessary care services.

8.
FASEB J ; 37(3): e22792, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36723904

RESUMO

Cistanche tubulosa (Schrenk) Wight, named Guan hua Rou Cong-Rong in Chinese, is a traditional plant with liver, kidney, and intestine protective effects. Echinacoside (ECH) is its active constituent and has been found to have various biological effects, including antioxidative stress and anti-inflammatory effects. Liver injury caused by acetaminophen or CCL4 has been proven to benefit from ECH; however, the effects of ECH against alcoholic liver disease (ALD) remain unclear. This study was used to estimate the effect of echinacoside on nuclear factor erythroid 2-related factor 2 (Nrf2), which ameliorates ALD by inhibiting oxidative stress and cell apoptosis through affecting Nrf2.A mouse model of ALD was established with ethanol using hematoxylin and eosin (HE) staining, oiled staining, and biochemical indices. Alpha Mouse Liver 12 (AML-12) cells were induced with ethanol in vitro and analyzed using western blotting, flow cytometry, and biochemical assays. In the animal model of ALD, ECH dramatically reduced liver damage, as proven by the downregulation of aspartate aminotransferase (AST) and HE staining. In vitro, ECH distinctly reduced the damage caused by ethanol through the decreased expression of cleaved caspase-3 measured by western blotting. ECH significantly increased the activity of Nrf2 in vivo and in vitro. Nrf2 knockout may diminish the influence of ECH on ALD. Meanwhile, ECH also increased the expression of haem oxygenase-1 (HO-1) and glutamate-cysteine ligase catalytic subunit (GCLC), while it inhibited levels of oxidative stress and cell apoptosis. Our findings suggest that ECH protects against ethanol-induced liver injuries by alleviating oxidative stress and cell apoptosis by increasing the activity of Nrf2. Therefore, ECH is promising for the treatment of ALD.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Cistanche , Camundongos , Animais , Cistanche/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Fígado/metabolismo , Estresse Oxidativo , Etanol/toxicidade
9.
Respir Res ; 24(1): 37, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36721187

RESUMO

BACKGROUND: Our previous studies have suggested that bromodomain protein 4 (BRD4) is increased in the lung of stable chronic obstructive pulmonary disease (COPD) patients, which has been shown to be involved in inflammatory responses. We investigated its role in the viral exacerbation of COPD. METHODS: BRD4, interleukin (IL)-6 and IL-8 were measured in the blood and sputum of stable COPD patients and patients with viral exacerbation. Mice were exposed to cigarette smoke (CS) and/or infected with influenza virus as an in vivo model. BRD4, IL-6 and keratinocyte-derived chemokine (KC) were measured in the lung. BEAS-2B cells were treated with CS extract and/or influenza virus as an in vitro model. BRD4, IL-6 and IL-8 were measured in the cells and/or culture supernatant. RESULTS: BRD4 was increased in COPD patients with viral exacerbation compared with those in stable condition and its expression was correlated with IL-6 and IL-8 expression. Inflammatory cells, IL-6, KC and BRD4 were synergistically induced in the lung of mice by viral infection and CS exposure, and the former three were decreased by JQ1 (BRD4 inhibitor) treatment. IL-6, IL-8 and BRD4 were significantly induced by CS extract and influenza virus in bronchial epithelial cells, and this upregulation was suppressed by knockdown of BRD4 expression. CONCLUSIONS: Our findings indicate that CS and viruses may synergistically induce IL-6 and IL-8 expression through their synergistic induction of BRD4 expression, which might contribute to the enhanced inflammatory response in the viral exacerbation of COPD.


Assuntos
Proteínas de Ciclo Celular , Proteínas Nucleares , Doença Pulmonar Obstrutiva Crônica , Fatores de Transcrição , Animais , Camundongos , Interleucina-6 , Interleucina-8 , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Humanos , Proteínas de Ciclo Celular/genética
10.
BMC Med ; 21(1): 35, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36721200

RESUMO

BACKGROUND: Congenital heart diseases (CHDs) remain a significant cause of infant morbidity and mortality. Epidemiological studies have explored maternal risk factors for offspring CHDs, but few have used genetic epidemiology methods to improve causal inference. METHODS: Three birth cohorts, including 65,510 mother/offspring pairs (N = 562 CHD cases) were included. We used Mendelian randomisation (MR) analyses to explore the effects of genetically predicted maternal body mass index (BMI), smoking and alcohol on offspring CHDs. We generated genetic risk scores (GRS) using summary data from large-scale genome-wide association studies (GWAS) and validated the strength and relevance of the genetic instrument for exposure levels during pregnancy. Logistic regression was used to estimate the odds ratio (OR) of CHD per 1 standard deviation (SD) higher GRS. Results for the three cohorts were combined using random-effects meta-analyses. We performed several sensitivity analyses including multivariable MR to check the robustness of our findings. RESULTS: The GRSs associated with the exposures during pregnancy in all three cohorts. The associations of the GRS for maternal BMI with offspring CHD (pooled OR (95% confidence interval) per 1SD higher GRS: 0.95 (0.88, 1.03)), lifetime smoking (pooled OR: 1.01 (0.93, 1.09)) and alcoholic drinks per week (pooled OR: 1.06 (0.98, 1.15)) were close to the null. Sensitivity analyses yielded similar results. CONCLUSIONS: Our results do not provide robust evidence of an effect of maternal BMI, smoking or alcohol on offspring CHDs. However, results were imprecise. Our findings need to be replicated, and highlight the need for more and larger studies with maternal and offspring genotype and offspring CHD data.


Assuntos
Estudo de Associação Genômica Ampla , Cardiopatias Congênitas , Fumar , Feminino , Humanos , Lactente , Gravidez , Índice de Massa Corporal , Etanol , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/genética , Fumar/efeitos adversos , Fumar/epidemiologia , Análise da Randomização Mendeliana
11.
Ren Fail ; 45(1): 2170243, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36721891

RESUMO

INTRODUCTION: To estimate the up-to-date prevalence of chronic kidney disease among the health check-up population in economically developed areas of China using estimated glomerular filtration rate, urinary albumin creatinine ratio, and kidney ultrasound. METHODS: Healthcare data from 38,093 subjects in 10 megalopolises of China who had an annual health check-up in 2021 were used. The overall and stratified prevalence of chronic kidney disease by sex, age, region and comorbidity group was reported. The association between chronic kidney disease and covariates of demographics, and comorbidities were analyzed in the multivariable-adjusted logistic regression model. RESULTS: A total of 3837 CKD cases were detected meeting any of the three CKD diagnostic criteria, with a crude prevalence of 10.1% in the study population. Using one criterion of decreased glomerular filtration rate, albuminuria and kidney structural abnormalities alone detected 204 (5.3%), 3289 (85.7%) and 563 (14.7%) cases, respectively. The addition of kidney ultrasound detected 427 (11.1%) structural abnormality cases without decreased GFR and albuminuria. The most common abnormalities were renal masses, hydronephrosis due to obstruction and congenital anomalies of kidney and urinary tract. Female, older age, low city-tier, hypertension, diabetes, obesity, hypertriglyceridemia as well as early disease stages such as pre-hypertension, impaired fasting glucose and overweight were significantly associated with chronic kidney disease. CONCLUSION: Kidney ultrasound helps to amplify the detection of CKD patients, which is a supplement to kidney function and urine protein.


Assuntos
Albuminúria , Insuficiência Renal Crônica , Humanos , Feminino , Estudos Transversais , Albuminúria/epidemiologia , Prevalência , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Fatores de Risco , Rim , China/epidemiologia
12.
Proc Biol Sci ; 290(1992): 20221986, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36722077

RESUMO

Vaccination has been critical to the decline in infectious disease prevalence in recent centuries. Nonetheless, vaccine refusal has increased in recent years, with complacency associated with reductions in disease prevalence highlighted as an important contributor. We exploit a natural experiment in Glasgow at the beginning of the twentieth century to investigate whether prior local experience of an infectious disease matters for vaccination decisions. Our study is based on smallpox surveillance data and administrative records of parental refusal to vaccinate their infants. We analyse variation between administrative units of Glasgow in cases and deaths from smallpox during two epidemics over the period 1900-1904, and vaccine refusal following its legalization in Scotland in 1907 after a long period of compulsory vaccination. We find that lower local disease incidence and mortality during the epidemics were associated with higher rates of subsequent vaccine refusal. This finding indicates that complacency influenced vaccination decisions in periods of higher infectious disease risk, responding to local prior experience of the relevant disease, and has not emerged solely in the context of the generally low levels of infectious disease risk of recent decades. These results suggest that vaccine delivery strategies may benefit from information on local variation in incidence.


Assuntos
Doenças Transmissíveis , Epidemias , Varíola , Lactente , Humanos , Doenças Transmissíveis/epidemiologia , Escócia , Recusa de Vacinação
13.
Alzheimers Dement ; 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36722399

RESUMO

BACKGROUND: We studied the effect of apolipoprotein E (APOE) ε4 status and sex on age of symptom onset (AO) in early- (EO) and late- (LO) onset Alzheimer's disease (AD). METHOD: A total of 998 EOAD and 2562 LOAD participants from the National Alzheimer's Coordinating Center (NACC) were included. We used analysis of variance to examine AO differences between sexes and APOE genotypes and the effect of APOE ε4, sex, and their interaction on AO in EOAD and LOAD, separately. RESULTS: APOE ε4 carriers in LOAD had younger AO and in EOAD had older AO. Female EOAD APOE ε4 carriers had older AO compared to non-carriers (P < 0.0001). There was no difference for males. Both male and female LOAD APOE ε4 carriers had younger AO relative to non-carriers (P < 0.0001). CONCLUSION: The observed earlier AO in EOAD APOE ε4 non-carriers relative to carriers, particularly in females, suggests the presence of additional AD risk variants.

14.
Gut Microbes ; 15(1): 2172672, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36724123

RESUMO

The intimate association between the gut microbiota (GM) and the central nervous system points to potential intervention strategies for neurological diseases. Nevertheless, there is currently no theoretical framework for selecting the window period and target bacteria for GM interventions owing to the complexity of the gut microecosystem. In this study, we constructed a complex network-based modeling approach to evaluate the topological features of the GM and infer the window period and bacterial candidates for GM interventions. We used Alzheimer's disease (AD) as an example and traced the GM dynamic changes in AD and wild-type mice at one, two, three, six, and nine months of age. The results revealed alterations of the topological features of the GM from a scale-free network into a random network during AD progression, indicating severe GM disequilibrium at the late stage of AD. Through stability and vulnerability assessments of the GM networks, we identified the third month after birth as the optimal window period for GM interventions in AD mice. Further computational simulations and robustness evaluations determined that the hub bacteria were potential candidates for GM interventions. Moreover, our GM functional analysis suggested that Lachnospiraceae UCG-001 - the hub and enriched bacterium in AD mice - was the keystone bacterium for GM interventions owing to its contributions to quinolinic acid synthesis. In conclusion, this study established a complex network-based modeling approach as a practical strategy for disease interventions from the perspective of the gut microecosystem.


Assuntos
Doença de Alzheimer , Microbioma Gastrointestinal , Camundongos , Animais , Microbioma Gastrointestinal/fisiologia , Encéfalo , Bactérias/genética
15.
BMJ Open ; 13(2): e067960, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36725091

RESUMO

OBJECTIVES: Religious affiliation, beliefs, and practices shape lifestyles and disease risks. This study examined Hindu-Muslim differences in the prevalence and management of hypertension and diabetes in Bangladesh, a religiously plural country with 91% Muslims and 8% Hindus. DESIGN, SETTINGS AND PARTICIPANTS: We used the nationally representative 2011 Bangladesh Demographic and Health Survey (BDHS) and 2017-2018 BDHS data. The 2011 BDHS collected blood pressure (BP) data with an 89% response rate (RR) and fasting blood glucose (FBG) data (RR 85%) from household members aged 35 years and above. The 2017-2018 BDHS collected BP and FBG data from household members aged 18 years and above with 89% and 84% RRs, respectively. We analysed 6628 participants for hypertension and 6370 participants for diabetes from the 2011 BDHS, 11 449 for hypertension and 10 744 for diabetes from the 2017-2018 BDHS. METHODS: We followed the WHO guidelines to define hypertension and diabetes. We used descriptive statistics and multiple logistic regression to examine the Hindu-Muslim differences in hypertension and diabetes, and estimated predicted probabilities to examine the changes in hypertension and diabetes risk over time. RESULTS: Nine in 10 of the sample were Muslims. About 31% of Hindus and 24% of Muslims were hypertensive; 10% of both Hindus and Muslims were diabetic in 2017-2018. The odds of being hypertensive were 45% higher among Hindus than Muslims (adjusted OR: 1.45; 95% CI: 1.23 to 1.71; p<0.001). The levels of awareness, medication and control of hypertension were similar between the religious groups. Between the 2011 and 2017-2018 BDHS, the Hindu-Muslim difference in the prevalence of hypertension increased non-significantly, by 3 percentage points. CONCLUSIONS: Further studies on religious-based lifestyles, Hindu-Muslim differences in diet, physical activity, stress, and other risk factors of hypertension and diabetes are needed to understand Hindus' higher likelihood of being hypertensive, in contrast, not diabetic compared with Muslims.


Assuntos
Diabetes Mellitus , Hipertensão , Humanos , Estudos Transversais , Bangladesh/epidemiologia , Hipertensão/epidemiologia , Hipertensão/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Islamismo , Prevalência
16.
BMJ Open ; 13(2): e064944, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36725090

RESUMO

INTRODUCTION: Early relapse in Crohn's disease (CD) is associated with a more severe disease course. The microbiome plays a crucial role, yet strategies targeting the microbiome are underrepresented in current guidelines. We hypothesise that early manipulation of the microbiome will improve clinical response to standard-of-care (SOC) induction therapy in patients with a relapse-associated microbiome profile. We describe the protocol of a pilot study assessing feasibility of treatment allocation based on baseline faecal microbiome profiles. METHODS AND ANALYSIS: This is a 52-week, multicentre, randomised, controlled, open-label, add-on pilot study to test the feasibility of a larger multicontinent trial evaluating the efficacy of adjuvant antibiotic therapy in 20 paediatric patients with mild-to-moderate-CD (10

Assuntos
Doença de Crohn , Microbiota , Humanos , Criança , Doença de Crohn/tratamento farmacológico , Azitromicina/uso terapêutico , Metronidazol/uso terapêutico , Projetos Piloto , Quimioterapia de Indução/métodos , Metagenoma , Teorema de Bayes , RNA Ribossômico 16S , Antibacterianos/uso terapêutico , Indução de Remissão , Recidiva , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
17.
BMJ Open ; 13(2): e064169, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36725099

RESUMO

OBJECTIVES: Motor neuron disease (MND) is an incurable progressive neurodegenerative disease with limited treatment options. There is a pressing need for innovation in identifying therapies to take to clinical trial. Here, we detail a systematic and structured evidence-based approach to inform consensus decision making to select the first two drugs for evaluation in Motor Neuron Disease-Systematic Multi-arm Adaptive Randomised Trial (MND-SMART: NCT04302870), an adaptive platform trial. We aim to identify and prioritise candidate drugs which have the best available evidence for efficacy, acceptable safety profiles and are feasible for evaluation within the trial protocol. METHODS: We conducted a two-stage systematic review to identify potential neuroprotective interventions. First, we reviewed clinical studies in MND, Alzheimer's disease, Huntington's disease, Parkinson's disease and multiple sclerosis, identifying drugs described in at least one MND publication or publications in two or more other diseases. We scored and ranked drugs using a metric evaluating safety, efficacy, study size and study quality. In stage two, we reviewed efficacy of drugs in MND animal models, multicellular eukaryotic models and human induced pluripotent stem cell (iPSC) studies. An expert panel reviewed candidate drugs over two shortlisting rounds and a final selection round, considering the systematic review findings, late breaking evidence, mechanistic plausibility, safety, tolerability and feasibility of evaluation in MND-SMART. RESULTS: From the clinical review, we identified 595 interventions. 66 drugs met our drug/disease logic. Of these, 22 drugs with supportive clinical and preclinical evidence were shortlisted at round 1. Seven drugs proceeded to round 2. The panel reached a consensus to evaluate memantine and trazodone as the first two arms of MND-SMART. DISCUSSION: For future drug selection, we will incorporate automation tools, text-mining and machine learning techniques to the systematic reviews and consider data generated from other domains, including high-throughput phenotypic screening of human iPSCs.


Assuntos
Esclerose Amiotrófica Lateral , Células-Tronco Pluripotentes Induzidas , Doença dos Neurônios Motores , Doenças Neurodegenerativas , Humanos , Esclerose Amiotrófica Lateral/tratamento farmacológico , Consenso , Doença dos Neurônios Motores/tratamento farmacológico
18.
BMC Biol ; 21(1): 17, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36726088

RESUMO

BACKGROUND: The majority of genes in the human genome is present in two copies but the expression levels of both alleles is not equal. Allelic imbalance is an aspect of gene expression relevant not only in the context of genetic variation, but also to understand the pathophysiology of genes implicated in genetic disorders, in particular, dominant genetic diseases where patients possess one normal and one mutant allele. Polyglutamine (polyQ) diseases are caused by the expansion of CAG trinucleotide tracts within specific genes. Spinocerebellar ataxia type 3 (SCA3) and Huntington's disease (HD) patients harbor one normal and one mutant allele that differ in the length of CAG tracts. However, assessing the expression level of individual alleles is challenging due to the presence of abundant CAG repeats in the human transcriptome, which make difficult the design of allele-specific methods, as well as of therapeutic strategies to selectively engage CAG sequences in mutant transcripts. RESULTS: To precisely quantify expression in an allele-specific manner, we used SNP variants that are linked to either normal or CAG expanded alleles of the ataxin-3 (ATXN3) and huntingtin (HTT) genes in selected patient-derived cell lines. We applied a SNP-based quantitative droplet digital PCR (ddPCR) protocol for precise determination of the levels of transcripts in cellular and mouse models. For HD, we showed that the process of cell differentiation can affect the ratio between endogenous alleles of HTT mRNA. Additionally, we reported changes in the absolute number of the ATXN3 and HTT transcripts per cell during neuronal differentiation. We also implemented our assay to reliably monitor, in an allele-specific manner, the silencing efficiency of mRNA-targeting therapeutic approaches for HD. Finally, using the humanized Hu128/21 HD mouse model, we showed that the ratio of normal and mutant HTT transgene expression in brain slightly changes with the age of mice. CONCLUSIONS: Using allele-specific ddPCR assays, we observed differences in allele expression levels in the context of SCA3 and HD. Our allele-selective approach is a reliable and quantitative method to analyze low abundant transcripts and is performed with high accuracy and reproducibility. Therefore, the use of this approach can significantly improve understanding of allele-related mechanisms, e.g., related with mRNA processing that may be affected in polyQ diseases.


Assuntos
Proteínas Repressoras , Expansão das Repetições de Trinucleotídeos , Humanos , Camundongos , Animais , Alelos , Ataxina-3/genética , Ataxina-3/metabolismo , Reprodutibilidade dos Testes , Expansão das Repetições de Trinucleotídeos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína Huntingtina/genética , Proteínas Repressoras/genética
19.
J Transl Med ; 21(1): 65, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36726156

RESUMO

BACKGROUND: Cerebral small vessel disease (CSVD) is a systemic disease, affecting not only the brain, but also eyes and other organs. The total CSVD score is a tool for comprehensive evaluation of brain lesions in patients with CSVD. The ophthalmic artery (OA) is a direct response to ocular blood flow. However, little is known about the correlation between CSVD and characteristics of OA. We investigated the OA morphologies and hemodynamics in patients with CSVD and the correlation between these changes and the total CSVD score. METHODS: This cross-sectional observational study included 34 eyes from 22 patients with CSVD and 10 eyes from 5 healthy controls. The total CSVD score was rated according to the CSVD signs on magnetic resonance imaging. OA morphological characteristics were measured on the basis of 3D OA model reconstruction. OA hemodynamic information was calculated using computational fluid dynamics simulations. RESULTS: The total CSVD score negatively correlated with the OA diameter, blood flow velocity, and mass flow ratio (all P < 0.05). After adjusting for potential confounding factors, the total CSVD score was still independently correlated with the OA blood velocity (ß = - 0.202, P = 0.005). The total CSVD score was not correlated with OA angle (P > 0.05). The presence of cerebral microbleeds and enlarged perivascular spaces was correlated with the OA diameter (both P < 0.01), while the lacunar infarcts and white matter hyperintensities were correlated with the OA blood velocity (both P < 0.001). CONCLUSIONS: The decrease of the blood velocity in the OA was associated with the increase in the total CSVD score. The changes of the OA diameter and velocity were associated with the presence of various CSVD signs. The findings suggest that more studies are needed in the future to evaluate CSVD by observing the morphologies and hemodynamics of OA.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Acidente Vascular Cerebral Lacunar , Humanos , Estudos Transversais , Artéria Oftálmica/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/complicações , Acidente Vascular Cerebral Lacunar/complicações , Imageamento por Ressonância Magnética , Hemodinâmica
20.
Int J Angiol ; 32(1): 1-10, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36727145

RESUMO

Moderate intensity exercise is considered as a primary step to prevent coronary artery diseases (CADs) by stimulated FSTL-1 secretion as a novel myokines to improve endothelial cell function, prevent arterial stiffness, or vascular inflammation. This review aims to provide the current evident role of FSTL-1 as a novel myokine secreted during exercise to prevent atherosclerosis progression. A systematic review using databases from (PubMed), ScienceDirect, and The Cochrane Library, was conducted up to October 2021 to identify all the eligible experimental and observational studies that assess how moderate intensity exercises stimulate FSTL-1 secretion to prevent atherosclerosis. Results were described through narrative synthesis of the evidence. From 84 retrieved references, 15 studies met the inclusion criteria and were included in this review. The overall results suggest that exercise or physical activity can stimulate myokines secretion, especially in FSTL-1. FSTL-1 is a myokine or adipokine that plays a potential role in preventing atherosclerosis by various mechanisms such as via improvement of endothelial functions, suppression of smooth muscle cells (SMCs) proliferation, and reduction of arterial thickening. FSTL-1 is a relatively new and less known myokine, but probably holds a key role in assessing how moderate intensity aerobic exercise prevents atherosclerosis progression by preventing endothelial dysfunction, arterial stiffness, or vascular inflammation.

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