Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Proc Natl Acad Sci U S A ; 118(34)2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34376550

RESUMO

Quantification of asymptomatic infections is fundamental for effective public health responses to the COVID-19 pandemic. Discrepancies regarding the extent of asymptomaticity have arisen from inconsistent terminology as well as conflation of index and secondary cases which biases toward lower asymptomaticity. We searched PubMed, Embase, Web of Science, and World Health Organization Global Research Database on COVID-19 between January 1, 2020 and April 2, 2021 to identify studies that reported silent infections at the time of testing, whether presymptomatic or asymptomatic. Index cases were removed to minimize representational bias that would result in overestimation of symptomaticity. By analyzing over 350 studies, we estimate that the percentage of infections that never developed clinical symptoms, and thus were truly asymptomatic, was 35.1% (95% CI: 30.7 to 39.9%). At the time of testing, 42.8% (95% prediction interval: 5.2 to 91.1%) of cases exhibited no symptoms, a group comprising both asymptomatic and presymptomatic infections. Asymptomaticity was significantly lower among the elderly, at 19.7% (95% CI: 12.7 to 29.4%) compared with children at 46.7% (95% CI: 32.0 to 62.0%). We also found that cases with comorbidities had significantly lower asymptomaticity compared to cases with no underlying medical conditions. Without proactive policies to detect asymptomatic infections, such as rapid contact tracing, prolonged efforts for pandemic control may be needed even in the presence of vaccination.


Assuntos
Infecções Assintomáticas/epidemiologia , COVID-19/epidemiologia , COVID-19/diagnóstico , COVID-19/virologia , Humanos , SARS-CoV-2/isolamento & purificação
2.
BMC Public Health ; 22(1): 1042, 2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35614429

RESUMO

BACKGROUND: Nunavut, the northernmost Arctic territory of Canada, experienced three community outbreaks of the coronavirus disease 2019 (COVID-19) from early November 2020 to mid-June 2021. We sought to investigate how non-pharmaceutical interventions (NPIs) and vaccination affected the course of these outbreaks. METHODS: We used an agent-based model of disease transmission to simulate COVID-19 outbreaks in Nunavut. The model encapsulated demographics and household structure of the population, the effect of NPIs, and daily number of vaccine doses administered. We fitted the model to inferred, back-calculated infections from incidence data reported from October 2020 to June 2021. We then compared the fit of the scenario based on case count data with several counterfactual scenarios without the effect of NPIs, without vaccination, and with a hypothetical accelerated vaccination program whereby 98% of the vaccine supply was administered to eligible individuals. RESULTS: We found that, without a territory-wide lockdown during the first COVID-19 outbreak in November 2020, the peak of infections would have been 4.7 times higher with a total of 5,404 (95% CrI: 5,015-5,798) infections before the start of vaccination on January 6, 2021. Without effective NPIs, we estimated a total of 4,290 (95% CrI: 3,880-4,708) infections during the second outbreak under the pace of vaccination administered in Nunavut. In a hypothetical accelerated vaccine rollout, the total infections during the second Nunavut outbreak would have been 58% lower, to 1,812 (95% CrI: 1,593-2,039) infections. Vaccination was estimated to have the largest impact during the outbreak in April 2021, averting 15,196 (95% CrI: 14,798-15,591) infections if the disease had spread through Nunavut communities. Accelerated vaccination would have further reduced the total infections to 243 (95% CrI: 222-265) even in the absence of NPIs. CONCLUSIONS: NPIs have been essential in mitigating pandemic outbreaks in this large, geographically distanced and remote territory. While vaccination has the greatest impact to prevent infection and severe outcomes, public health implementation of NPIs play an essential role in the short term before attaining high levels of immunity in the population.


Assuntos
COVID-19 , Vacinas , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Canadá , Controle de Doenças Transmissíveis , Surtos de Doenças/prevenção & controle , Humanos , Nunavut/epidemiologia , SARS-CoV-2 , Vacinação
3.
Biochem Genet ; 59(1): 31-41, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32720141

RESUMO

Deregulation of the renin-angiotensin system (RAS) plays an important role in suicide. Angiotensin converting enzyme (ACE) gene is a key component in this system. The relationship between insertion/deletion (I/D) polymorphism of ACE gene with suicide attempt (SA) is controversial. According to previous studies, allele D in this polymorphism has been considered as a potential risk factor for suicide. However, no study has been conducted in Iran to investigate this matter. This case-control study has focused on investigating the association of ACE I/D polymorphism (rs1799752) with SA in an Iranian population. The frequency of genotypes was 14% for II, 55% for ID, and 31% for DD in the case group (100 persons), and 18% for II, 74% for ID, and 8% for DD in control group (100 persons). Results show there was a significant difference in the distribution of ACE I/D polymorphism genotypes in men with SA compared to controls, as well as in women with SA compared to controls. Also, there was a significant association between DD genotype and the risk of SA compared to II genotype as reference. The severity of depression was significantly different between DD and II genotypes in SA group. According to the results, we suggest that the presence of DD genotype is possibly associated with an increased risk of SA. Maybe part of that is related to severity of depression in DD genotypes carriers of ACE I/D polymorphism.


Assuntos
Depressão/genética , Mutação INDEL , Peptidil Dipeptidase A/genética , Polimorfismo de Nucleotídeo Único , Tentativa de Suicídio , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Escalas de Graduação Psiquiátrica , Fatores de Risco , Índice de Gravidade de Doença , Suicídio , Adulto Jovem
4.
BMC Med ; 18(1): 230, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32709232

RESUMO

BACKGROUND: The province of Ontario, Canada, has instituted indefinite school closures (SC) as well as other social distancing measures to mitigate the impact of the novel coronavirus disease 2019 (COVID-19) pandemic. We sought to evaluate the effect of SC on reducing attack rate and the need for critical care during COVID-19 outbreaks, while considering scenarios with concurrent implementation of self-isolation (SI) of symptomatic cases. METHODS: We developed an age-structured agent-based simulation model and parameterized it with the demographics of Ontario stratified by age and the latest estimates of COVID-19 epidemiologic characteristics. Disease transmission was simulated within and between different age groups by considering inter- and intra-group contact patterns. The effect of SC of varying durations on the overall attack rate, magnitude and peak time of the outbreak, and requirement for intensive care unit (ICU) admission in the population was estimated. Secondly, the effect of concurrent community-based voluntary SI of symptomatic COVID-19 cases was assessed. RESULTS: SC reduced attack rates in the range of 7.2-12.7% when the duration of SC increased from 3 to 16 weeks, when contacts among school children were restricted by 60-80%, and in the absence of SI by mildly symptomatic persons. Depending on the scenario, the overall reduction in ICU admissions attributed to SC throughout the outbreak ranged from 3.3 to 6.7%. When SI of mildly symptomatic persons was included and practiced by 20%, the reduction of attack rate and ICU admissions exceeded 6.3% and 9.1% (on average), respectively, in the corresponding scenarios. CONCLUSION: Our results indicate that SC may have limited impact on reducing the burden of COVID-19 without measures to interrupt the chain of transmission during both pre-symptomatic and symptomatic stages. While highlighting the importance of SI, our findings indicate the need for better understanding of the epidemiologic characteristics of emerging diseases on the effectiveness of social distancing measures.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Coronavirus/patogenicidade , Pneumonia Viral/epidemiologia , Instituições Acadêmicas/estatística & dados numéricos , COVID-19 , Criança , Infecções por Coronavirus/transmissão , Humanos , Ontário/epidemiologia , Pandemias , Pneumonia Viral/transmissão , SARS-CoV-2
5.
CMAJ ; 192(25): E666-E670, 2020 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444481

RESUMO

BACKGROUND: Estimates of the case-fatality rate (CFR) associated with coronavirus disease 2019 (COVID-19) vary widely in different population settings. We sought to estimate and compare the COVID-19 CFR in Canada and the United States while adjusting for 2 potential biases in crude CFR. METHODS: We used the daily incidence of confirmed COVID-19 cases and deaths in Canada and the US from Jan. 31 to Apr. 22, 2020. We applied a statistical method to minimize bias in the crude CFR by accounting for the survival interval as the lag time between disease onset and death, while considering reporting rates of COVID-19 cases less than 50% (95% confidence interval 10%-50%). RESULTS: Using data for confirmed cases in Canada, we estimated the crude CFR to be 4.9% on Apr. 22, 2020, and the adjusted CFR to be 5.5% (credible interval [CrI] 4.9%-6.4%). After we accounted for various reporting rates less than 50%, the adjusted CFR was estimated at 1.6% (CrI 0.7%-3.1%). The US crude CFR was estimated to be 5.4% on Apr. 20, 2020, with an adjusted CFR of 6.1% (CrI 5.4%-6.9%). With reporting rates of less than 50%, the adjusted CFR for the US was 1.78 (CrI 0.8%-3.6%). INTERPRETATION: Our estimates suggest that, if the reporting rate is less than 50%, the adjusted CFR of COVID-19 in Canada is likely to be less than 2%. The CFR estimates for the US were higher than those for Canada, but the adjusted CFR still remained below 2%. Quantification of case reporting can provide a more accurate measure of the virulence and disease burden of severe acute respiratory syndrome coronavirus 2.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/mortalidade , Surtos de Doenças/estatística & dados numéricos , Pandemias/estatística & dados numéricos , Pneumonia Viral/mortalidade , COVID-19 , Canadá/epidemiologia , Humanos , Incidência , SARS-CoV-2 , Fatores de Tempo , Estados Unidos/epidemiologia
6.
CMAJ ; 192(46): E1482-E1486, 2020 11 16.
Artigo em Francês | MEDLINE | ID: mdl-33199459

RESUMO

CONTEXTE: Les estimations du taux de létalité de la maladie à coronavirus 2019 (COVID-19) varient grandement selon les populations. L'objectif était d'estimer et de comparer ce taux pour le Canada et les États-Unis en tenant compte de 2 sources de biais potentiel du taux brut. MÉTHODES: Pour ce faire, nous sommes partis du nombre quotidien de cas confirmés et de décès au Canada et aux États-Unis pour la période du 31 janvier au 22 avril 2020. Nous y avons appliqué une méthode statistique qui réduit au minimum les biais du taux de létalité brut de 2 façons : en intégrant la durée de survie, soit le délai entre le début de la maladie et le décès, et en considérant que moins de 50 % des cas de COVID-19 sont confirmés (intervalle de confiance à 95 % 10 %­50 %). RÉSULTATS: À partir du nombre de cas confirmés au Canada, nous avons évalué le taux brut en date en 22 avril 2020 à 4,9 %, et le taux ajusté à 5,5 % (intervalle de crédibilité [ICr] 4,9 %­6,4 %). En appliquant divers taux de cas confirmés inférieurs à 50 %, nous avons obtenu un taux ajusté de 1,6 % (ICr 0,7 %­3,1 %). Pour les États-Unis, le taux brut en date du 20 avril 2020 était de 5,4 %, et le taux ajusté, de 6,1 % (ICr 5,4 %­6,9 %). Combiné à des taux de cas confirmés inférieurs à 50 %, le taux ajusté est passé à 1,78 % (ICr 0,8 %­3,6 %). INTERPRÉTATION: Nos estimations montrent que si le taux de cas confirmés est de moins de 50 %, le taux de létalité ajusté de la COVID-19 est vraisemblablement inférieur à 2 % au Canada. Aux États-Unis, les estimations sont plus élevées, mais le taux ajusté reste sous la barre des 2 %. Si le taux de cas confirmés était connu, nous pourrions mieux évaluer la virulence du coronavirus du syndrome respiratoire aigu sévère 2 et la charge associée.

7.
ACS Pharmacol Transl Sci ; 7(1): 48-71, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38230282

RESUMO

Berberine is a well-known phytochemical with significant antiviral activity against a wide range of viruses. Due to having a unique backbone consisting of four interconnected rings, it can be used as a platform for the design and development of novel semisynthetic antiviral agents. The question here is whether novel broad-spectrum antiviral drugs with enhanced activity and toxicity potential can be obtained by attempting to modify the structure of this privileged lead compound. The present study aims to review the results of recent studies in which berberine and its close analogues (protoberberine alkaloids) have been used as starting materials for the production of new semisynthetic antiviral structures. For this purpose, relevant studies published in high-quality journals indexed in databases such as Scopus, Web of Science, PubMed, etc. in the time frame of 2017 to 2023 were collected. Our selection criterion in the current review focuses on the studies in which protoberberines were used as starting materials for the production of semisynthetic agents with antiviral activity during the indicated time period. Correspondingly, studies were identified in which semisynthetic derivatives with significant inhibitory activity against a wide range of viruses including human immunodeficiency virus (HIV), enterovirus 71 (EV71), zika virus (ZIKV), influenza A/B, cytomegalovirus (CMV), respiratory syncytial virus (RSV), and coxsackieviruses were designed and synthesized. Our conclusion is that, despite the introduction of diverse semisynthetic derivatives of berberine with improved activity profiles compared to the parent natural leads, sufficient derivatization has not been done yet and more studies are needed.

8.
Lancet Reg Health Am ; 28: 100629, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38026446

RESUMO

Background: The cost-effectiveness of immunisation strategies with a long-acting monoclonal antibody (nirsevimab) and/or a protein-based maternal vaccine (RSVpreF) for protecting infants from Respiratory Syncytial Virus (RSV)-associated illness has not been previously determined for Canada. We estimated the health benefits and cost-effectiveness of nirsevimab for immunising the entire birth cohort, regardless of gestational age or other risk factors. Additionally, we evaluated the health benefits and cost-effectiveness of a combined strategy of year-round vaccination of pregnant women with RSVpreF and immunisation of infants at high risk, including those born preterm or with chronic conditions, with nirsevimab during the RSV season. Methods: We developed a discrete-event simulation model, parameterized with the data on medically-attended RSV infections among infants under one year of age from 2010 to 2019, including outpatient care, hospitalisations, and deaths. Intervention scenarios targeting twelve monthly birth cohorts and pregnant women, reflecting the 2021 census data for Ontario, Canada were evaluated over a follow-up time horizon of one year from birth. Taking into account the costs (in 2023 Canadian dollars) associated with RSV-related outcomes, we calculated the net monetary benefit using the quality-adjusted life-year (QALY) gained. Further, we determined the range of price-per-dose (PPD) for nirsevimab and RSVpreF within which the program was cost-effective. Cost-effectiveness analyses were conducted from both healthcare and societal perspectives. Findings: Using a willingness-to-pay of CAD$50,000 per QALY gained, we found that immunising the entire birth cohort with nirsevimab would be cost-effective from a societal perspective for a PPD of up to $290, with an annual budget impact of $83,978 for 1113 infants per 100,000 population. An alternative, combined strategy of vaccinating pregnant women and immunising only infants at high risk of severe disease would lead to a lower budget impact of $49,473 per 100,000 population with a PPD of $290 and $195 for nirsevimab and RSVpreF vaccine, respectively. This combined strategy would reduce infant mortality by 76%-85%, comparable to a 78% reduction achieved through a nirsevimab-only program of the entire birth cohort. The PPD for cost-effective programs with nirsevimab was sensitive to the target population among infants. Interpretation: Passive immunisation of infants under 6 months of age with nirsevimab and vaccination of pregnant women with RSVpreF could be a cost-effective strategy for protecting infants during their first RSV season. Funding: This study was supported by the Canadian Immunisation Research Network (CIRN) and the Canadian Institutes of Health Research (CIHR). Seyed M. Moghadas acknowledges support from the Natural Sciences and Engineering Research Council of Canada (MfPH and Discovery grants). Alison P. Galvani acknowledges support from the The Notsew Orm Sands Foundation.

9.
Front Neurol ; 13: 877143, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35968317

RESUMO

Introduction/Objectives: In addition to cognitive decline, one of the most important problems for caregivers of patients with Alzheimer's is neuropsychiatric symptoms (NPS). This study aimed to evaluate the NPS in patients with Alzheimer's disease (AD) and investigate its relationship with caregiver burden (CB). Methods: In a cross-sectional study of 85 patients with AD referred to Shafa Hospital in Rasht and their caregivers in 2020, information was collected using a demographic questionnaire, Neuropsychiatric Inventory Questionnaire (NPI-Q), and the Caregiver Burden Inventory (CBI). Data were analyzed by Spearman correlation, t-test, and linear regression, with SPSS version 22. Results: The mean age of the patients and their caregivers were 74.95 ± 8.87 years and 43.98 ± 11.38 years, respectively. The mean total score of NPS in patients with AD was 44.25 (0-144) and the mean CB score was 36.27 (0-96), which was a moderate level. According to the results, 91% of patients had apathy, while happiness/euphoria was reported as the most uncommon symptom. In addition, there was a significant relationship between the score of NPS and CB (r = 0.542, P < 0.0001), as well as all its sub-components, time-dependence burden with more correlation (r = 0.509, P < 0.0001), and social burden with less correlation (r = 0.352, P < 0.001). NPS, hallucination, aberrant motor behavior (AMB), delusion, and depression were most correlated with CB. Also, the mean score of CB was significantly higher in women than in men (P = 0.045). Living in a rural area had a significant relationship with NPS score (P = 0.026). Also, linear regression showed that with increasing 1 year of patients' age, the mean score of patient's NPS decreased by 0.374 (P = 0.048). Conclusion: Neuropsychiatric symptoms, especially hallucination, aberrant motor behavior (AMB), delusion, and depression were associated with caregiver burden. Apathy was the most common symptom in patients with AD.

10.
Eur J Pharmacol ; 918: 174715, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35026193

RESUMO

Evidence has demonstrated that a new class of anti-diabetic drugs, sodium-glucose co-transporter 2 (SGLT2) inhibitors, could exert beneficial effects on atherosclerotic complications of diabetes. Atherosclerosis is widely accepted as an inflammatory disease. Therefore, we aimed to assess the direct anti-inflammatory effects of SGLT2 inhibitors dapagliflozin (DAPA) on two cell types involved in the process of atherogenesis. Human umbilical vein endothelial cells (HUVECs) and macrophages were exposed to DAPA and lipopolysaccharide (LPS 20 ng/mL) for 24 h under normal (5.5 mmol/L, NG) or high glucose (25 mmol/L, HG) conditions. Then, levels of TLR-4/p-NF-κB, inflammatory cytokines, inflammation-related miR-146a and miR-155 as well as alteration in the ratio of M1/M2 macrophage polarization was assessed. DAPA (0.5 µM) could significantly attenuate LPS-induced TLR-4 overexpression (23.9% and 33.1% under NG and HG conditions in HUVECs and 53.3% and 52.4% under NG and HG states in macrophages, respectively). NF-κB p65 phosphorylation was also significantly decreased to 30.1% under NG condition in HUVECs and 51.9% and 34.5% under NG and HG states in macrophages by 0.5 µM DAPA. Moreover, DAPA elevated expression levels of anti-inflammatory miR-146a, while values of miR-155 decreased in those cells. DAPA also caused a shift from inflammatory M1 macrophages toward M2-dominant macrophages. These data suggest that regardless of glucose concentrations, DAPA could exert direct anti-inflammatory effects, at least partly, by inhibiting the expression of TLR-4 and activation of NF-κB along with the secretion of pro-inflammatory mediators.


Assuntos
Aterosclerose , Compostos Benzidrílicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosídeos/farmacologia , Células Endoteliais da Veia Umbilical Humana , Macrófagos , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Anti-Inflamatórios/farmacologia , Aterosclerose/tratamento farmacológico , Aterosclerose/imunologia , Aterosclerose/patologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/imunologia , Humanos , Hipoglicemiantes/farmacologia , Mediadores da Inflamação/antagonistas & inibidores , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Transdução de Sinais , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
11.
Sci Rep ; 12(1): 1336, 2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35079035

RESUMO

Schizophrenia is a severe, disabling psychiatric disorder with unclear etiology. Family-based, twins, and adoption studies have shown that genetic factors have major contributions in schizophrenia occurrence. Until now, many studies have discovered the association of schizophrenia and its comorbid symptoms with functional polymorphisms that lie within serotonin reuptake pathway genes. Here, we aimed to investigate the association of three variable number tandem repeats (VNTR) functional polymorphisms in MAOA and SLC6A4 with schizophrenia in the Iranian population. Two hundred and forty-one subjects with schizophrenia and three hundred and seventy age and sex-matched healthy controls were genotyped for MAOA promoter uVNTR, 5-HTTLPR, and STin2 polymorphisms. Genotyping was performed by polymerase chain reaction (PCR) with locus-specific primers and running the PCR product on agarose 2.5% gel electrophoresis. Finally, the statistical inference was performed using R programming language and Haploview software. MAOA promoter uVNTR analysis of allele frequency showed no differences between schizophrenia subjects and healthy controls in both males and females and no significant differences were observed between female cases and female controls in MAOA promoter uVNTR 4 repeat frequency. Also, there were no differences between Schizophrenia and healthy control groups in 5-HTTLPR allele and genotype frequency but, 5-HTTLPR S allele carriers are significantly more frequent among cases. In addition, STin2.12 repeats were significantly more frequent among schizophrenia patients. Genotype comparison suggested that 5-HTTLPR S allele and STin2.12 repeat carriers were significantly more frequent among schizophrenia cases and being STin2.12 repeat carrier significantly increase the risk of schizophrenia occurrence. Besides, analysis of haplotype showed stronger linkage disequilibrium between 5-HTTLPR and STin2 haplotype block in cases than controls. These results suggest that SLC6A4 functional polymorphisms potentially could play a possible role as risk factors for the incidence of schizophrenia.


Assuntos
Monoaminoxidase/genética , Esquizofrenia/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adulto , Estudos de Casos e Controles , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites , Polimorfismo de Nucleotídeo Único
12.
Infect Dis Model ; 7(4): 698-708, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36313153

RESUMO

Tuberculosis (TB) continues to disproportionately affect Inuit populations in Canada with some communities having over 300 times higher rate of active TB than Canadian-born, non-Indigenous people. Inuit Tuberculosis Elimination Framework has set the goal of reducing active TB incidence by at least 50% by 2025, aiming to eliminate it by 2030. Whether these goals are achievable with available resources and treatment regimens currently in practice has not been evaluated. We developed an agent-based model of TB transmission to evaluate timelines and milestones attainable in Nunavut, Canada by including case findings, contact-tracing and testing, treatment of latent TB infection (LTBI), and the government investment on housing infrastructure to reduce the average household size. The model was calibrated to ten years of TB incidence data, and simulated for 20 years to project program outcomes. We found that, under a range of plausible scenarios with tracing and testing of 25%-100% of frequent contacts of detected active cases, the goal of 50% reduction in annual incidence by 2025 is not achievable. If active TB cases are identified rapidly within one week of becoming symptomatic, then the annual incidence would reduce below 100 per 100,000 population, with 50% reduction being met between 2025 and 2030. Eliminating TB from Inuit populations would require high rates of contact-tracing and would extend beyond 2030. The findings indicate that time-to-identification of active TB is a critical factor determining program effectiveness, suggesting that investment in resources for rapid case detection is fundamental to controlling TB.

13.
J Reprod Immunol ; 143: 103266, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33385732

RESUMO

PURPOSE: Vitamin D (Vit D), as an immunomodulator, has been hypothesized to play a critical role in the pathogenesis of endometriosis. Thus, in this study, we evaluated whether there is an association between 25-hydroxyvitamin D [25(OH)D] and susceptibility to endometriosis in Iranian women. METHODS: Women at reproductive age, including 56 healthy women and 54 patients with endometriosis, were enrolled in the study. Serum levels of 25(OH)D, calcium, parathyroid hormone (PTH), and peritoneal fluid (PF) levels of 25(OH)D were assessed. RESULTS: The serum and PF levels of 25(OH)D in the patients with endometriosis were significantly lower than the control group (P = 0.001 and P = 0.03, respectively). Subjects with serum levels of 25(OH)D lower than 20 ng/mL had a 2.7 times higher risk of endometriosis than people with 25(OH)D serum levels higher than 20 ng/mL (non-deficient) (OR = 2.7, 95 % confidence interval: 1.24-5.80, P = 0.01). The serum levels of calcium and PTH were significantly lower and higher in patients with endometriosis compared with controls, respectively (P < 0.001, P = 0.02, respectively). Also, the serum levels of 25(OH)D were lower in stages I-II endometriosis than stage III-IV; however, no significant difference was observed. CONCLUSION: Our findings showed that people with Vit D deficiency are at higher risk of endometriosis.


Assuntos
Endometriose/epidemiologia , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adolescente , Adulto , Cálcio/sangue , Estudos de Casos e Controles , Endometriose/sangue , Endometriose/diagnóstico , Endometriose/imunologia , Feminino , Voluntários Saudáveis , Humanos , Irã (Geográfico)/epidemiologia , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fatores de Risco , Vitamina D/sangue , Vitamina D/imunologia , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/imunologia , Adulto Jovem
14.
Iran J Allergy Asthma Immunol ; 19(6): 602-611, 2020 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-33463129

RESUMO

The T-cell immunoglobulin and mucin-3 (TIM-3)/galectin-9 (Gal-9) autocrine loop is an indispensable signaling in acute myeloid leukemia (AML) cells, which induces their self-renewal through activation of nuclear factor-kappa b (NF-kB) and ß-catenin pathways. In this study, we evaluated the effects of oridonin and doxorubicin on the TIM-3/Gal-9 autocrine loop. We also evaluated oridonin anti-inflammatory and anti-cancer properties on U937 cells, as an AML cell line in comparison to doxorubicin as a common anthracycline drug for AML treatment. Cell counting kit-8 (CCK-8) was applied to evaluate the cytotoxicity of oridonin and doxorubicin on U937 cells and also to determine the impact of galectin-9 (Gal-9) on their proliferation. The effects of oridonin and doxorubicin on Gal-9, TIM-3, and interleukin-1ß (IL-1ß) gene expression were determined by real-time polymerase chain reaction (RT-PCR). The Gal-9 secretion level was measured by enzyme-linked immunosorbent assay (ELISA) and activation of NF-kB pathway was assessed by western blotting. In a dose-dependent manner, oridonin and doxorubicin were capable to eradicate U937 cells while Gal-9 expanded them. Following the treatment of U937 cells with oridonin, the expression of Gal-9, TIM-3, and IL-1ß genes was down-regulated, and the Gal-9 secretion and NF-kB phosphorylation were diminished, whereas doxorubicin increased all of these factors. Doxorubicin is a common treatment agent in AML, but it may induce inflammation and up-regulate the TIM3/Gal-9 autocrine loop, consequently can enhance the possibility of disease relapse. Meanwhile, oridonin is capable to inhibit the essential signaling pathways in AML cells and reduce the inflammation and expansion of tumor cells and postpone AML recurrence.


Assuntos
Diterpenos do Tipo Caurano/farmacologia , Galectinas/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Imunoglobulinas/metabolismo , Inflamação/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Linhagem Celular Tumoral , Doxorrubicina , Humanos , Inflamação/metabolismo , Leucemia Mieloide Aguda/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/metabolismo , Células U937
15.
Gene ; 706: 13-18, 2019 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-31034941

RESUMO

BACKGROUND: Metabolic syndrome is a cluster of conditions that increase risk of cardiovascular morbidity and mortality. Among genetic factors that contributed to incidence of metabolic syndrome, Polymorphisms of Lipoprotein lipase (LPL) are major candidates especially because of their effect on obesity and dyslipidemia. S447X (rs328) and Hind III (rs320) Polymorphisms of LPL gene have been reported to change LPL activity, resulting in altered triglyceride (TG) and high density lipoprotein Cholesterol (HDL-C) levels. This study investigates the effects of these gene polymorphisms on factors affecting metabolic syndrome in northern population of Iran. METHODS: Studied population included 223 adults consisting 90 women and 133 men with body mass index (BMI) ≥ 30 kg/m2 as obese subjects, and 156 healthy participants as a control group with BMI <25 that included 68 women and 88 men. All factors causing metabolic syndrome were evaluated. Also DNA was extracted from blood samples and HindIII and S447X LPL gene polymorphisms were screened by polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). CONCLUSIONS: The present study proves that some genotypes of S447X were associated with a reduced risk of developing low HDL-C only in men, while the protective effects of HindIII on hypertriglyceridemia were only seen in women [corrected]. The point is that this relation is affected by the weight profile of the participants. It can be concluded that there is a gender-related relation between the polymorphisms of LPL gene and the risk factors for incidence of metabolic syndrome in the northern population of Iran.


Assuntos
Lipase Lipoproteica/genética , Síndrome Metabólica/genética , Adulto , Índice de Massa Corporal , Dislipidemias/genética , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Hipertrigliceridemia/genética , Irã (Geográfico) , Lipídeos/sangue , Lipase Lipoproteica/fisiologia , Masculino , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Obesidade/sangue , Polimorfismo de Nucleotídeo Único/genética , Fatores Sexuais , Triglicerídeos/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA