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1.
J Environ Sci (China) ; 125: 843-850, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36375966

RESUMO

With a unique and large size of testing results of 1,842 samples collected from 12 wastewater treatment plants (WWTP) for 14 months through from low to high prevalence of COVID-19, the sensitivity of RT-qPCR detection of SARS-CoV-2 RNA in wastewater that correspond to the communities was computed by using Probit analysis. This study determined the number of new COVID-19 cases per 100,000 population required to detect SARS-CoV-2 RNA in wastewater at defined probabilities and provided an evidence-based framework of wastewater-based epidemiology surveillance (WBE). Input data were positive and negative test results of SARS-CoV-2 RNA in wastewater samples and the corresponding new COVID-19 case rates per 100,000 population served by each WWTP. The analyses determined that RT-qPCR-based SARS-CoV-2 RNA detection threshold at 50%, 80% and 99% probability required a median of 8 (range: 4-19), 18 (9-43), and 38 (17-97) of new COVID-19 cases /100,000, respectively. Namely, the positive detection rate at 50%, 80% and 99% probability were 0.01%, 0.02%, and 0.04% averagely for new cases in the population. This study improves understanding of the performance of WBE SARS-CoV-2 RNA detection using the large datasets and prolonged study period. Estimated COVID-19 burden at a community level that would result in a positive detection of SARS-CoV-2 in wastewater is critical to support WBE application as a supplementary warning/monitoring system for COVID-19 prevention and control.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2/genética , Águas Residuárias/análise , RNA Viral/genética , RNA Viral/análise , Alberta/epidemiologia
2.
Clin Infect Dis ; 62(10): 1251-1258, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-26917812

RESUMO

BACKGROUND: Antibiotic administration to individuals with Shiga toxin-producing Escherichia coli (STEC) infection remains controversial. We assessed if antibiotic administration to individuals with STEC infection is associated with development of hemolytic uremic syndrome (HUS). METHODS: The analysis included studies published up to 29 April 2015, that provided data from patients (1) with STEC infection, (2) who received antibiotics, (3) who developed HUS, and (4) for whom data reported timing of antibiotic administration in relation to HUS. Risk of bias was assessed; strength of evidence was adjudicated. HUS was the primary outcome. Secondary outcomes restricted the analysis to low-risk-of-bias studies employing commonly used HUS criteria. Pooled estimates of the odds ratio (OR) were obtained using random-effects models. RESULTS: Seventeen reports and 1896 patients met eligibility; 8 (47%) studies were retrospective, 5 (29%) were prospective cohort, 3 (18%) were case-control, and 1 was a trial. The pooled OR, including all studies, associating antibiotic administration and development of HUS was 1.33 (95% confidence interval [CI], .89-1.99; I(2) = 42%). The repeat analysis including only studies with a low risk of bias and those employing an appropriate definition of HUS yielded an OR of 2.24 (95% CI, 1.45-3.46; I(2) = 0%). CONCLUSIONS: Overall, use of antibiotics was not associated with an increased risk of developing HUS; however, after excluding studies at high risk of bias and those that did not employ an acceptable definition of HUS, there was a significant association. Consequently, the use of antibiotics in individuals with STEC infections is not recommended.


Assuntos
Antibacterianos , Infecções por Escherichia coli , Síndrome Hemolítico-Urêmica , Escherichia coli Shiga Toxigênica , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Síndrome Hemolítico-Urêmica/tratamento farmacológico , Síndrome Hemolítico-Urêmica/epidemiologia , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Escherichia coli Shiga Toxigênica/efeitos dos fármacos , Escherichia coli Shiga Toxigênica/patogenicidade
3.
BMC Pediatr ; 15: 89, 2015 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-26226953

RESUMO

BACKGROUND: Each year in Canada there are 5 million episodes of acute gastroenteritis (AGE) with up to 70% attributed to an unidentified pathogen. Moreover, 90% of individuals with AGE do not seek care when ill, thus, burden of disease estimates are limited by under-diagnosing and under-reporting. Further, little is known about the pathogens causing AGE as the majority of episodes are attributed to an "unidentified" etiology. Our team has two main objectives: 1) to improve health through enhanced enteric pathogen identification; 2) to develop economic models incorporating pathogen burden and societal preferences to inform enteric vaccine decision making. METHODS/DESIGN: This project involves multiple stages: 1) Molecular microbiology experts will participate in a modified Delphi process designed to define criteria to aid in interpreting positive molecular enteric pathogen test results. 2) Clinical data and specimens will be collected from children aged 0-18 years, with vomiting and/or diarrhea who seek medical care in emergency departments, primary care clinics and from those who contact a provincial medical advice line but who do not seek care. Samples to be collected will include stool, rectal swabs (N = 2), and an oral swab. Specimens will be tested employing 1) stool culture; 2) in-house multiplex (N = 5) viral polymerase chain reaction (PCR) panel; and 3) multi-target (N = 15) PCR commercially available array. All participants will have follow-up data collected 14 days later to enable calculation of a Modified Vesikari Scale score and a Burden of Disease Index. Specimens will also be collected from asymptomatic children during their well child vaccination visits to a provincial public health clinic. Following the completion of the initial phases, discrete choice experiments will be conducted to enable a better understanding of societal preferences for diagnostic testing and vaccine policy. All of the results obtained will be integrated into economic models. DISCUSSION: This study is collecting novel samples (e.g., oral swabs) from previously untested groups of children (e.g., those not seeking medical care) which are then undergoing extensive molecular testing to shed a new perspective on the epidemiology of AGE. The knowledge gained will provide the broadest understanding of the epidemiology of vomiting and diarrhea of children to date.


Assuntos
Gastroenterite/epidemiologia , Doença Aguda , Adolescente , Alberta/epidemiologia , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Diarreia/microbiologia , Fezes/microbiologia , Gastroenterite/economia , Gastroenterite/microbiologia , Humanos , Lactente , Recém-Nascido , Técnicas Microbiológicas , Modelos Econômicos , Índice de Gravidade de Doença , Manejo de Espécimes , Vômito/microbiologia
4.
Sex Transm Dis ; 40(9): 744-50, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23945428

RESUMO

BACKGROUND: Antimicrobial resistance testing and behavioral data combined with Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) can help to define gonococcal populations and identify, characterize, and compare clusters of infection. METHODS: Antimicrobial resistance testing, using E test, was reviewed for gonococcal isolates in Alberta, Canada, from 2007 to 2011. Antimicrobial resistance testing was conducted on isolates demonstrating antimicrobial resistance and those with cefixime minimum inhibitory concentrations (MICs) of 0.06 µg/mL or greater. Demographic and behavioral information was obtained from provincial surveillance data. NG-MAST typing was conducted on a proportion of isolates. RESULTS: Gonococcal isolates were available for 2250 (26.4%) of 8535 cases of gonorrhea in Alberta from 2007 to 2011. The proportion of cases with decreased susceptibility to cefixime (≥0.06 µg/mL) increased from 0.7% to 2.4% between 2007 and 2009 to a high of 10.1% in 2010 and 8.9% in 2011. Six isolates with cefixime MIC of 0.25 µg/mL were noted: 5 were from men who have sex with men (MSM) and 1 was a pharyngeal isolate from a heterosexual female. Twenty-four (1.1%) isolates were azithromycin resistant (MIC ≥2.0 µg/mL); there were no significant differences between cases resistant or susceptible to azithromycin. NG-MAST of gonococcal isolates in Alberta suggests the entry of multiple strains into the province. Three clusters were identified: Cluster A predominantly in MSM, including sequence type 1407, a ST previously associated with decreased susceptibility to expanded spectrum cephalosporins; Cluster B, a predominantly heterosexual cluster with most cases in Edmonton; and Cluster C among MSM. CONCLUSIONS: Our data highlight the use of NG-MAST in further defining gonococcal populations.


Assuntos
Antibacterianos/farmacologia , Antígenos de Bactérias/genética , Farmacorresistência Bacteriana , Gonorreia/epidemiologia , Neisseria gonorrhoeae/isolamento & purificação , Alberta/epidemiologia , Azitromicina/farmacologia , Técnicas de Tipagem Bacteriana , Cefixima/farmacologia , Ceftriaxona/farmacologia , Cefalosporinas/farmacologia , DNA Bacteriano/química , DNA Bacteriano/genética , Feminino , Gonorreia/tratamento farmacológico , Heterossexualidade , Homossexualidade Feminina , Homossexualidade Masculina , Humanos , Masculino , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Neisseria gonorrhoeae/classificação , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Filogenia , Estudos Retrospectivos
6.
Br J Radiol ; 96(1146): 20220852, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37001054

RESUMO

OBJECTIVES: To measure the magnitude of intra-fraction prostate motion (IFPM) during stereotactic radiotherapy (SBRT) delivered without intra-fraction tracking.To assess if current margins adequately cover IFPM.To derive margins using new guidelines. METHODS: IFPM was determined in 20 patients receiving 36.25 Gy in 5 fractions using 97 pairs of pre- and post-treatment cone beam CT (CBCT) scans. Correlation of time between CBCT acquisitions and motion was determined. The magnitude of IFPM was compared to current margins (6 mm isotropic, 3 mm posterior). Margins were calculated using IFPM alone and updated guidelines. RESULTS: The averaged 3D root mean square IFPM was 2.5 mm (4.2 mm). Independent prostate motion was predominantly posterior (70%) and inferior (63%). There was weak correlation between posterior (ρ = 0.38) and inferior (ρ = 0.36) IFPM and time. IFPM greater than current margins occurred in 8 of 97 fractions, six in the posterior direction. Margins were ≤3.5 mm using IFPM alone and ≤3.3 mm Left 3.5 mm Right, 7.0 mm inferior, 3.7 mm superior, 4.4 mm anterior and 3.3 mm posterior using new guidelines, compensating for motion in 92% of fractions. CONCLUSIONS: Our current SBRT margins account for 92% of IFPM, predominantly posterior and inferior. Although updated guidelines suggest an increase in margins inferiorly, any increase must be balanced against the possibility of increased toxicity, particularly if biochemical control and side-effects are favourable with current practice. ADVANCES IN KNOWLEDGE: The difference between current clinical margins and those determined using updated guidance is demonstrated. The implications must be considered against clinical outcomes.


Assuntos
Neoplasias da Próstata , Radiocirurgia , Radioterapia Guiada por Imagem , Masculino , Humanos , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Incerteza , Movimento (Física) , Tomografia Computadorizada de Feixe Cônico , Planejamento da Radioterapia Assistida por Computador
7.
Int J Radiat Oncol Biol Phys ; 115(2): 305-316, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36150450

RESUMO

PURPOSE: Our purpose was to report 5-year efficacy and toxicity of intraprostatic lesion boosting using standard and hypofractionated radiation therapy. METHODS AND MATERIALS: DELINEATE (ISRCTN 04483921) is a single center phase 2 multicohort study including standardly fractionated (cohort A: 74 Gy/37F to prostate and seminal vesicles [PSV]; cohort C 74 Gy/37F to PSV plus 60 Gy/37F to pelvic lymph nodes) and moderately hypofractionated (cohort B: 60 Gy/20F to PSV) prostate intensity-modulated radiation therapy patients with National Comprehensive Cancer Network intermediate/high-risk disease. Patients received an integrated boost of 82 Gy (cohorts A and C) or 67 Gy (cohort B) to multiparametric magnetic resonance imaging identified lesion(s). Primary endpoint was late Radiation Therapy Oncology Group (RTOG) gastrointestinal (GI) toxicity at 1 year. Secondary endpoints were acute and late toxicity (clinician and patient reported) and freedom from biochemical/clinical failure at 5 years. RESULTS: Two hundred and sixty-five men were recruited and 256 were treated (55 cohort A, 153 cohort B, and 48 cohort C). Median follow-up for each cohort was >5 years. Cumulative late RTOG grade 2+ GI toxicity at 1 year was 3.6% (95% confidence interval [CI], 0.9%-13.8%) (cohort A), 7.2% (95% CI, 4%-12.6%) (cohort B), and 8.4% (95% CI, 3.2%-20.8%) (cohort C). Cumulative late RTOG grade 2+ GI toxicity to 5 years was 12.8% (95% CI, 6.3%-25.1%) (cohort A), 14.6% (95% CI, 9.9%-21.4%) (cohort B), and 20.7% (95% CI, 11.2%-36.2%) (cohort C). Cumulative RTOG grade 2+ genitourinary toxicity to 5 years was 12.9% (95% CI, 6.4%-25.2%) (cohort A), 18.2% (95% CI, 12.8%-25.4%) (cohort B), and 18.2% (95% CI, 9.5%-33.2%) (cohort C). Five-year freedom from biochemical/clinical failure was 98.2% (95% CI, 87.8%-99.7%) (cohort A), 96.7% (95% CI, 91.3%- 98.8%) (cohort B), and 95.1% (95% CI, 81.6-98.7%) (cohort C). CONCLUSIONS: The DELINEATE trial has shown safety, tolerability, and feasibility of focal boosting in 20 or 37 fractions. Efficacy results indicate a low chance of prostate cancer recurrence 5 years after radiation therapy. Evidence from ongoing phase 3 randomized trials is awaited.


Assuntos
Gastroenteropatias , Neoplasias da Próstata , Radioterapia de Intensidade Modulada , Humanos , Masculino , Gastroenteropatias/etiologia , Recidiva Local de Neoplasia/etiologia , Próstata/patologia , Neoplasias da Próstata/patologia , Hipofracionamento da Dose de Radiação , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos
8.
Front Vet Sci ; 10: 1060759, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36937023

RESUMO

Background: Equine coronavirus (ECoV) leads to outbreaks with variable morbidity and mortality. Few previous reports of risk factors for infection are available in the literature. Objectives: To describe unique clinical findings and risk factors for infection and development of clinical disease. Animals: 135 horses on a farm affected by ECoV outbreak. Methods: Retrospective cohort study. Data obtained included age, breed, gender, activity level, housing, and feed at the onset of the outbreak. Factors were evaluated for assessment of risk of infection using simple logistic regression or Fisher's exact test. Significance was set at p ≤ 0.05. Results and findings: Forty-three of 54 (79.6%) horses tested on the farm were positive on fecal PCR for ECoV, and 17 horses (12.6%) developed clinical signs consistent with ECoV. Out of 17 horses in which the presence or absence of signs of colic was noted, 6 of 17 (35.3%) showed signs of colic. Three of these horses had small colon impactions, 2 of which required surgical intervention. Significant risk factors for having positive PCR results included being primarily stalled (OR 167.1, 95% CI 26.4-1719), housing next to a positive horse (OR 7.5, 95% CI 3.1-19.0), being in work (OR 26.9, 95% CI 4.6-281.9), being fed rationed hay vs. ad libitum (OR 1,558, 95% CI 130.8-15,593), and being fed alfalfa hay (OR 1,558, 95% CI 130.8-15,593). Conclusions and clinical importance: This report describes risk factors for ECoV infection many of which were associated with intensive management of show horses. Clinicians should be aware that clinical signs vary and can include severe colic.

9.
Radiother Oncol ; 187: 109810, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37468069

RESUMO

Irradiation of the vertebrae in prepubertal patients, if non-homogenous, can result in future growth deformities including kyphoscoliosis. Vertebral delineation and dosimetry were assessed for 101 paediatric cases reviewed within QUARTET-affiliated trials. Despite the availability of published consensus guidelines, a high variability in vertebral delineation was observed, with impact on dosimetry.


Assuntos
Radioterapia (Especialidade) , Coluna Vertebral , Criança , Humanos , Previsões , Ensaios Clínicos como Assunto
10.
ACS ES T Water ; 2(11): 2243-2254, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36380772

RESUMO

The correlations between SARS-CoV-2 RNA levels in wastewater from 12 wastewater treatment plants and new COVID-19 cases in the corresponding sewersheds of 10 communities were studied over 17 months. The analysis from the longest continuous surveillance reported to date revealed that SARS-CoV-2 RNA levels correlated well with temporal changes of COVID-19 cases in each community. The strongest correlation was found during the third wave (r = 0.97) based on the population-weighted SARS-CoV-2 RNA levels in wastewater. Different correlations were observed (r from 0.51 to 0.86) in various sizes of communities. The population in the sewershed had no observed effects on the strength of the correlation. Fluctuation of SARS-CoV-2 RNA levels in wastewater mirrored increases and decreases of COVID-19 cases in the corresponding community. Since the viral shedding to sewers from all infected individuals is included, wastewater-based surveillance provides an unbiased and no-discriminate estimation of the prevalence of COVID-19 compared with clinical testing that was subject to testing-seeking behaviors and policy changes. Wastewater-based surveillance on SARS-CoV-2 represents a temporal trend of COVID-19 disease burden and is an effective and supplementary monitoring when the number of COVID-19 cases reaches detectable thresholds of SARS-CoV-2 RNA in wastewater of treatment facilities serving various sizes of populations.

11.
Radiother Oncol ; 158: 97-103, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33636231

RESUMO

PURPOSE/OBJECTIVE: Total body irradiation (TBI) remains a key component of conditioning for allogeneic haemopoietic stem cell transplant (HSCT), with interstitial pneumonitis (IP) and chronic kidney disease (CKD) important late sequelae. We undertook a retrospective service evaluation of TBI patients treated with a forward-planned intensity modulated radiotherapy technique (FP IMRT). MATERIAL/METHODS: 74 adult patients were identified; all received step and shoot FP IMRT TBI, 14.4 Gy in 8 fractions over 4 days. Mean doses to the lungs and kidneys were 12-12.5 Gy. Toxicities were defined as per CTCAE v4.0: IP as multilobar infiltrates on CT with symptoms of dyspnoea, and renal dysfunction as an Estimated Glomerular Filtration rate (eGFR) < 60 ml/min/1.73 m2 for > 3 months. Secondary endpoints were overall survival (OS), progression free survival (PFS), cumulative incidence of non-relapse mortality (NRM), relapse risk and of acute and chronic GvHD. RESULTS: Patients received treatment for the following diagnosis: ALL/LBL (n = 37); AML (n = 33), CML-BC (n = 2) and High grade NHL (n = 2). The rate of IP due to any cause was 30%; positive microbiological evidence in 73% (16 /22). Idiopathic IP was seen in 8%, with only 4% (n = 3) having IP Grade ≥ 3. Two (4%) of 52 long term survivors developed CKD, one with thrombotic microangiopathy. 4 year NRM was 16% (CI 11-32%); no treatment related deaths in matched sibling or umbilical cord blood HSCT. CONCLUSION: FP IMRT TBI, reducing dose to the lungs and kidneys, has lower rates of idiopathic IP and CKD compared to the literature. This technique is safe and effective conditioning for full intensity HSCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doenças Pulmonares Intersticiais , Radioterapia de Intensidade Modulada , Insuficiência Renal Crônica , Adulto , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo , Irradiação Corporal Total/efeitos adversos
13.
Can J Public Health ; 101(6): 454-8, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21370780

RESUMO

OBJECTIVE: We describe a centralized automated multi-function detection and reporting system for public health surveillance--the Alberta Real Time Syndromic Surveillance Net (ARTSSN). This improves upon traditional paper-based systems which are often fragmented, limited by incomplete data collection and inadequate analytical capacity, and incapable of providing timely information for public health action. METHODS: ARTSSN concurrently analyzes multiple electronic data sources in real time to describe results in tables, charts and maps. Detected anomalies are immediately disseminated via alerts to decision-makers for action. RESULTS: ARTSSN provides richly integrated information on a variety of health conditions for early detection of and prompt action on abnormal events such as clusters, outbreaks and trends. Examples of such health conditions include chronic and communicable disease, injury and environment-mediated adverse incidents. DISCUSSION: Key advantages of ARTSSN over traditional paper-based methods are its timeliness, comprehensiveness and automation. Public health surveillance of communicable disease, injury, environmental hazard exposure and chronic disease now occurs in a single system in real time year round. Examples are given to demonstrate the public health value of this system, particularly during Pandemic (H1N1) 2009.


Assuntos
Surtos de Doenças/prevenção & controle , Vigilância da População/métodos , Informática em Saúde Pública/métodos , Alberta/epidemiologia , Humanos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/epidemiologia , Influenza Humana/virologia , Informática em Saúde Pública/instrumentação
14.
J Civ Struct Health Monit ; 10(5): 861-881, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33442503

RESUMO

One of the most prevalent causes of bridge failure around the world is "scour"-the gradual erosion of soil around a bridge foundation due to fast-flowing water. A reliable technique for monitoring scour would help bridge engineers take timely countermeasures to safeguard against failure. Although vibration-based techniques for monitoring structural damage have had limited success, primarily due to insufficient sensitivity, these have tended to focus on the detection of local damage. High natural frequency sensitivity has recently been reported for scour damage. Previous experiments to investigate this have been limited as a result of the cost of full-scale testing and the fact that scaled-down soil-structure models tested outside a centrifuge do not adequately simulate full-scale behaviour. This paper describes the development of what is believed to be the first-ever centrifuge-testing programme to establish the sensitivity of bridge natural frequency to scour. A 1/60 scale model of a two-span integral bridge with 15 m spans was tested at varying levels of scour. For the fundamental mode of vibration, these tests found up to a 40% variation in natural frequency for 30% loss of embedment. Models of three other types of foundation, which represent a shallow pad foundation, a deep pile bent and a deep monopile, were also tested in the centrifuge at different scour levels. The shallow foundation model showed lower frequency sensitivity to scour than the deep foundation models. Another important finding is that the frequency sensitivity to "global scour" is slightly higher than the sensitivity to "local scour", for all foundation types. The level of frequency sensitivity (3.1-44% per scour depth equivalent to 30% of embedment of scour) detected in this experiment demonstrates the potential for using natural frequency as an indicator of both local and global scour of bridges, particularly those with deep foundations.

15.
Bioorg Med Chem ; 17(7): 2902-12, 2009 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-19269833

RESUMO

Abscisic acid (ABA) is a carotenoid-derived plant hormone known to regulate critical functions in growth, development and responses to environmental stress. The key enzyme which carries out the first committed step in ABA biosynthesis is the carotenoid cleavage 9-cis-epoxycarotenoid dioxygenase (NCED). We have developed a series of sulfur and nitrogen-containing compounds as potential ABA biosynthesis inhibitors of the NCED, based on modification of the sesquiterpenoid segment of the 9-cis-xanthophyll substrates and product. In in vitro assays, three sesquiterpene-like carotenoid cleavage dioxygenase (SLCCD) inhibitor compounds 13, 17 and 18 were found to act as inhibitors of Arabidopsis thaliana NCED 3 (AtNCED3) with K(i)'s of 93, 57 and 87 microM, respectively. Computational docking to a model of AtNCED3 supports a mechanism of inhibition through coordination of the heteroatom with the non-heme iron in the enzyme active site. In pilot studies, pretreatment of osmotically stressed Arabidopsis plants with compound 13 resulted lower levels of ABA and catabolite accumulation compared to levels in mannitol-stressed plant controls. This same inhibitor moderated known ABA-induced gene regulation effects and was only weakly active in inhibition of seed germination. Interestingly, all three inhibitors led to moderation of the stress-induced transcription of AtNCED3 itself, which could further contribute to lowering ABA biosynthesis in planta. Overall, these sesquiterpenoid-like inhibitors present new tools for controlling and investigating ABA biosynthesis and regulation.


Assuntos
Ácido Abscísico/biossíntese , Arabidopsis/enzimologia , Compostos Bicíclicos com Pontes/química , Compostos Bicíclicos com Pontes/síntese química , Cicloexanonas/química , Heptanos/química , Heptanos/síntese química , Oxigenases/antagonistas & inibidores , Reguladores de Crescimento de Plantas/síntese química , Sesquiterpenos/síntese química , Compostos Bicíclicos com Pontes/farmacologia , Simulação por Computador , Cicloexanonas/síntese química , Cicloexanonas/farmacologia , Dioxigenases/antagonistas & inibidores , Dioxigenases/metabolismo , Regulação para Baixo , Desenho de Fármacos , Regulação da Expressão Gênica de Plantas , Germinação/efeitos dos fármacos , Heptanos/farmacologia , Cinética , Oxigenases/metabolismo , Reguladores de Crescimento de Plantas/química , Reguladores de Crescimento de Plantas/farmacologia , Proteínas de Plantas , Sesquiterpenos/química , Sesquiterpenos/farmacologia
16.
Harm Reduct J ; 6: 30, 2009 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-19919709

RESUMO

BACKGROUND: Five cases of severe neutropenia (neutrophil counts < 0.5 per 109 cells/L) associated with exposure to cocaine and levamisole, an antihelimithic agent no longer available in Canada, were identified in Alberta in 2008. Alberta and British Columbia (BC) public health officials issued an advisory and urged health care professionals to report cases to public health. This paper presents the findings of the public health investigations. METHODS: Cases were identified prospectively through reporting by clinicians and a retrospective review of laboratory and medical examiners data from January 1, 2006 to March 31, 2009. Cases were categorized as confirmed, probable or suspect. Only the confirmed and probable cases are included in this paper. RESULTS: We compare cases of severe neutropenia associated with tainted cocaine (NATC) identified in Alberta and BC between January 1, 2008 to March 31, 2009. Of the 42 NATC cases: 23(55%) were from Alberta; 19(45%) were from British Columbia; 57% of these cases reported crack cocaine use (93% of those who identified type of cocaine used); 7% reported using cocaine powder; and the main route of cocaine administration was from smoking (72%). Fifty percent of the NATC cases had multiple episodes of neutropenia associated with cocaine use. Cases typically presented with bacterial/fungal infections and fever. One Alberta NATC case produced anti-neutrophil antibodies, and four were positive for anti-neutrophil cytoplasmic antibody (ANCA). Analysis of two crack pipes and one drug sample obtained from NATC cases confirmed the presence of both cocaine and levamisole. A further 18 cases were identified through the retrospective review of laboratory and medical examiner data in Alberta INTERPRETATION: Our findings support a link between neutropenia and levamisole tainted cocaine; particularly from smoking the crack form of cocaine. Some patients may be genetically predisposed to develop levamisole-related neutropenia. Awareness of the differential diagnosis will assist clinicians with case timely detection and appropriate management.

17.
Dev Comp Immunol ; 86: 47-51, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29704519

RESUMO

Hemocyanin is a multi-functional protein located in the hemolymph (blood) of certain arthropods and molluscs. In addition to its well-defined role in oxygen transport, hemocyanin can be converted into a phenoloxidase-like enzyme. Herein, we tested the antimicrobial properties of horseshoe crab (Limulus polyphemus) hemocyanin-derived phenoloxidase reaction products using broad ranges of phenolic substrates (e.g. l-DOPA) and microbial targets (Gram-positive/negative bacteria, yeast). The enzyme-catalysed turnover of several substrates generated (by)products that reduced significantly the number of colony forming units. Microbicidal effects of hemocyanin-derived phenoloxidase were thwarted by the inhibitor phenylthiourea. Data presented here further support a role for hemocyanin in invertebrate innate immunity.


Assuntos
Anti-Infecciosos/farmacologia , Hemocianinas/farmacologia , Caranguejos Ferradura/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Animais , Hemolinfa/imunologia
18.
Influenza Other Respir Viruses ; 11(1): 33-40, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27442911

RESUMO

BACKGROUND: Emergency department (ED) visit volumes can be especially high during the Christmas-New Year holidays, a period occurring during the influenza season in Canada. METHODS: Using daily data, we examined the relationship between ED visits for the chief complaint "cough" (for Edmonton, Alberta residents) and laboratory detections for influenza A and respiratory syncytial virus (RSV) (for Edmonton and surrounding areas), lagged 0-5 days ahead, for non-pandemic years (2004-2008 and 2010-2014) using multivariable linear regression adjusting for temporal variables. We defined these cough-related visits as influenza-like illness (ILI)-related ED visits and, for 2004-2014, compared Christmas-New Year holiday (December 24-January 3) and non-holiday volumes during the influenza season (October-April). RESULTS: Adjusting for temporal variables, ILI-related ED visits were significantly associated with laboratory detections for influenza A and RSV. During non-pandemic years, the highest peak in ILI-related visit volumes always occurred during the holidays. The median number of holiday ILI-related visits/day (42.5) was almost twice the non-holiday median (24) and was even higher in 2012-2013 (80) and 2013-2014 (86). Holiday ILI-related ED visit volumes/100 000 population ranged from 56.0 (2010-2011) to 117.4 (2012-2013). In contrast, lower visit volumes occurred during the holidays of pandemic-affected years (2008-2010). CONCLUSIONS: During non-pandemic years, ILI-related ED visit volumes were associated with variations in detections for influenza A and RSV and always peaked during the Christmas-New Year holidays. This predictability should be used to prepare for, and possibly prevent, this increase in healthcare use; however, interventions beyond disease prevention strategies are likely needed.


Assuntos
Técnicas de Laboratório Clínico/estatística & dados numéricos , Serviço Hospitalar de Emergência , Influenza Humana/diagnóstico , Vigilância da População , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções Respiratórias/diagnóstico , Adolescente , Adulto , Alberta/epidemiologia , Canadá/epidemiologia , Criança , Pré-Escolar , Surtos de Doenças/prevenção & controle , Surtos de Doenças/estatística & dados numéricos , Feminino , Humanos , Lactente , Recém-Nascido , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/epidemiologia , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Estações do Ano , Adulto Jovem
20.
Can J Public Health ; 107(2): e142-e148, 2016 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-27526210

RESUMO

OBJECTIVE: In June of 2013, southern Alberta underwent flooding that affected approximately 100,000 people. We describe the process put in place for public health surveillance and assessment of the impacts on health. METHODS: Public health surveillance was implemented for the six-week period after the flood to detect anticipated health events, including injuries, mental health problems and infectious diseases. Data sources were emergency departments (EDs) for presenting complaints, public health data on the post-exposure administration of tetanus vaccine/immunoglobulin, administrative data on prescription drugs, and reportable diseases. RESULTS: An increase in injuries was detected through ED visits among Calgary residents (rate ratio [RR] 1.28, 95% confidence interval [CI]: 1.14-1.43) and was supported by a 75% increase in the average weekly administration of post-exposure prophylaxis against tetanus. Mental health impacts in High River residents were observed among females through a 1.64-fold (95% CI: 1.11-2.43) and 2.32-fold (95% CI: 1.45-3.70) increase in new prescriptions for anti-anxiety medication and sleep aids respectively. An increase in sexual assaults presenting to EDs (RR 3.18, 95% CI: 1.29-7.84) was observed among Calgary residents. No increases in infectious gastrointestinal disease or respiratory illness were identified. Timely identification and communication of surveillance alerts allowed for messaging around the use of personal protective equipment and precautions for personal safety. CONCLUSION: Existing data sources were used for surveillance following an emergency situation. The information produced, though limited, was sufficiently timely to inform public health decision-making.


Assuntos
Inundações , Prática de Saúde Pública , Vigilância em Saúde Pública , Alberta/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Profilaxia Pós-Exposição/estatística & dados numéricos , Medicamentos sob Prescrição/uso terapêutico , Delitos Sexuais/estatística & dados numéricos , Tétano/prevenção & controle , Ferimentos e Lesões/epidemiologia
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