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1.
Cureus ; 15(11): e48933, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38106754

RESUMO

Intoxication by colchicine is rare, and its rapid recognition is crucial, as severe toxicity or death is reported in 10% of cases. Here, we present the case of a 50-year-old female admitted to the emergency department 24 hours after ingesting 10 mg of colchicine. Upon examination, she was conscious and hemodynamically stable. Analytically, she exhibited leukocytosis with neutrophilia and an elevation of lactate dehydrogenase (LDH). She was initiated on fluid therapy and transferred to the intermediate care unit of medicine. On the third day of hospitalization, she developed anterior chest pain, reduced breath sounds in the right hemithorax, and dullness on percussion. Arterial blood gas analysis showed partial respiratory failure, and chest X-rays and a computed tomography (CT) scan revealed a right-sided pleural effusion. The likely diagnosis was pleural effusion secondary to cardiac dysfunction due to colchicine intoxication. This case aims to describe the potential toxic effects of colchicine in cases of overdose and to reflect on ways to reduce its morbidity and mortality.

2.
NPJ Clean Water ; 6(1): 32, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37073161

RESUMO

Rainwater harvesting reliability, the proportion of days annually when rainwater demand is fully met, is challenging to estimate from cross-sectional household surveys that underpin international monitoring. This study investigated the use of a modelling approach that integrates household surveys with gridded precipitation data to evaluate rainwater harvesting reliability, using two local-scale household surveys in rural Siaya County, Kenya as an illustrative case study. We interviewed 234 households, administering a standard questionnaire that also identified the source of household stored drinking water. Logistic mixed effects models estimated stored rainwater availability from household and climatological variables, with random effects accounting for unobserved heterogeneity. Household rainwater availability was significantly associated with seasonality, storage capacity, and access to alternative improved water sources. Most households (95.1%) that consumed rainwater faced insufficient supply of rainwater available for potable needs throughout the year, with intermittencies during the short rains for most households with alternative improved sources. Although not significant, stored rainwater lasts longer for households whose only improved water source was rainwater (301.8 ± 40.2 days) compared to those having multiple improved sources (144.4 ± 63.7 days). Such modelling analysis could enable rainwater harvesting reliability estimation, and thereby national/international monitoring and targeted follow-up fieldwork to support rainwater harvesting.

3.
Sci Rep ; 12(1): 22426, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36575182

RESUMO

The objective of this work was to evaluate the kinetics and mineralization fraction of organic matter from sewage sludge mixed with the soil under controlled laboratory conditions. For this, organic material samples accumulated in layers 0-5 cm, 5-10 cm and 10-15 cm in relation to the surface of a vertical flow constructed wetland system (VF-CW) used for treatment of septic tank sludge, in addition to samples of dewatered sludge from a septic tank and a UASB reactor and non-dewatered sludge from an anaerobic digester were mixed with material collected from the surface layer of a Red Yellow Argisol at rates equivalent to the applications, via organic residues, of 300 and 600 kg ha-1 year-1 of total nitrogen. It was found that the two-phase kinetic equation fit better to the mineralization data of labile and recalcitrant organic carbon. For the lowest nitrogen application rate in the mixtures, the mineralization fractions of the total organic carbon were higher than 73%, while at the highest dose there was a reduction in the mineralization of organic matter by 17% and 63%, respectively in samples collected in layer 10-15 cm from the VF-CW and in the septic tank sludge dewatered in the drying bed.


Assuntos
Esgotos , Solo , Solo/química , Esgotos/química , Carbono , Áreas Alagadas , Nitrogênio/análise
5.
Animals (Basel) ; 12(17)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36077921

RESUMO

Accurate radiographic screening evaluation is essential in the genetic control of canine HD, however, the qualitative assessment of hip congruency introduces some subjectivity, leading to excessive variability in scoring. The main objective of this work was to validate a method-Hip Congruency Index (HCI)-capable of objectively measuring the relationship between the acetabulum and the femoral head and associating it with the level of congruency proposed by the Fédération Cynologique Internationale (FCI), with the aim of incorporating it into a computer vision model that classifies HD autonomously. A total of 200 dogs (400 hips) were randomly selected for the study. All radiographs were scored in five categories by an experienced examiner according to FCI criteria. Two examiners performed HCI measurements on 25 hip radiographs to study intra- and inter-examiner reliability and agreement. Additionally, each examiner measured HCI on their half of the study sample (100 dogs), and the results were compared between FCI categories. The paired t-test and the intraclass correlation coefficient (ICC) showed no evidence of a systematic bias, and there was excellent reliability between the measurements of the two examiners and examiners' sessions. Hips that were assigned an FCI grade of A (n = 120), B (n = 157), C (n = 68), D (n = 38) and E (n = 17) had a mean HCI of 0.739 ± 0.044, 0.666 ± 0.052, 0.605 ± 0.055, 0.494 ± 0.070 and 0.374 ± 0.122, respectively (ANOVA, p < 0.01). Therefore, these results show that HCI is a parameter capable of estimating hip congruency and has the potential to enrich conventional HD scoring criteria if incorporated into an artificial intelligence algorithm competent in diagnosing HD.

6.
Public Health Rep ; 137(6): 1178-1186, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35989593

RESUMO

OBJECTIVES: Information on the effectiveness of COVID-19 contact tracing is lacking. We proposed 2 measures for evaluating the effectiveness of contact tracing and applied them in a public health unit in northern Portugal. METHODS: This retrospective cohort study included the contacts of people with COVID-19 diagnosed July 1-September 15, 2020. We examined 2 measures: (1) number needed to quarantine (NNQ), as the number of quarantine person-days needed to prevent 1 potential infectious person-day; and (2) proportion of prevented infectious days by quarantine (PPID), as the number of potential infectious days prevented by quarantine divided by all infectious days. We assessed these measures by sociodemographic characteristics, types of contacts, and intervention timings (ie, time between diagnosis or symptom onset and intervention). We considered 3 scenarios for infectiousness periods: 10 days before to 10 days after symptom onset, 3 days before to 3 days after symptom onset, and 2 days before to 10 days after symptom onset. RESULTS: We found an NNQ of 19.8-41.8 person-days and a PPID of 19.7%-38.2%, depending on the infectiousness period scenario. Effectiveness was higher among cohabitants and symptomatic contacts than among social or asymptomatic contacts. NNQ and PPID changed by intervention timings: the effectiveness of contact tracing decreased with time from diagnosis to quarantine of contacts and with time from symptom onset of the index case to contacts' quarantine. CONCLUSIONS: These proposed measures of contact tracing effectiveness of communicable diseases can be important for decision making and prioritizing contact tracing when resources are scarce. They are also useful measures for communication with the general population, policy makers, and clinicians because they are easy to understand and use to assess the impact of health interventions.


Assuntos
COVID-19 , Doenças Transmissíveis , COVID-19/epidemiologia , COVID-19/prevenção & controle , Busca de Comunicante , Humanos , Quarentena , Estudos Retrospectivos , SARS-CoV-2
7.
Transbound Emerg Dis ; 69(4): 2182-2190, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34229362

RESUMO

Leishmaniasis is a neglected tropical disease that continues to pose a serious public health problem. Albeit dogs have long been held as the major reservoirs of Leishmania infantum, the involvement of domestic cats in the zoonotic cycle of visceral leishmaniasis has gained prominence. Here, 240 cats were evaluated by clinical signs and haematological/biochemical changes compatible with leishmaniasis and were diagnosed by serological, molecular, and parasitological techniques. Thus, four cats naturally infected by L. infantum were submitted to xenodiagnosis. A total of 203 females of Lutzomyia longipalpis were subjected to feeding on four cats, with all females completing the blood meal. Parasitological and molecular assays were carried out to evaluate the presence of L. infantum in the sand flies' midgut. Promastigotes were observed in 10 females (6.5%) that fed on one cat, and L. infantum DNA was detected in 17 (8.4%) females that fed on two cats. Our results strengthen the evidence that naturally infected cats are capable of transmitting L. infantum to sand flies.


Assuntos
Doenças do Gato , Leishmania infantum , Leishmaniose Visceral , Leishmaniose , Psychodidae , Animais , Doenças do Gato/diagnóstico , Gatos , Feminino , Leishmania infantum/genética , Leishmaniose/veterinária , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/veterinária , Masculino , Xenodiagnóstico/veterinária
8.
PLoS One ; 16(7): e0255286, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34320036

RESUMO

Water safety planning is an approach to ensure safe drinking-water access through comprehensive risk assessment and water supply management from catchment to consumer. However, its uptake remains low in rural areas. Participatory mapping, the process of map creation for resource management by local communities, has yet to be used for rural water safety planning. In this mixed methods study, to evaluate the validity of participatory mapping outputs for rural water safety planning and assess community understanding of water safety, 140 community members in Siaya County, Kenya, attended ten village-level participatory mapping sessions. They mapped drinking-water sources, ranked their safety and mapped potential contamination hazards. Findings were triangulated against a questionnaire survey of 234 households, conducted in parallel. In contrast to source type ranking for international monitoring, workshop participants ranked rainwater's safety above piped water and identified source types such as broken pipes not explicitly recorded in water source typologies often used for formal monitoring. Participatory mapping also highlighted the overlap between livestock grazing areas and household water sources. These findings were corroborated by the household survey and subsequent participatory meetings. However, comparison with household survey data suggested participatory mapping outputs omitted some water sources and landscape-scale contamination hazards, such as open defecation areas or flood-prone areas. In follow-up visits, participant groups ranked remediation of rainwater harvesting systems as the most acceptable intervention to address hazards. We conclude that participatory mapping can complement other established approaches to rural water safety planning by capturing informally managed source use and facilitating community engagement.


Assuntos
Água Potável/normas , Abastecimento de Água/normas , Adolescente , Adulto , Feminino , Humanos , Quênia , Masculino , Pessoa de Meia-Idade , Medição de Risco , População Rural , Inquéritos e Questionários , Abastecimento de Água/métodos , Adulto Jovem
9.
PLoS One ; 16(6): e0253321, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34166410

RESUMO

BACKGROUND: Antigen-detecting rapid diagnostic tests (Ag-RDTs) for the detection of SARS-CoV-2 offer new opportunities for testing in the context of the COVID-19 pandemic. Nasopharyngeal swabs (NPS) are the reference sample type, but oropharyngeal swabs (OPS) may be a more acceptable sample type in some patients. METHODS: We conducted a prospective study in a single screening center to assess the diagnostic performance of the Panbio™ COVID-19 Ag Rapid Test (Abbott) on OPS compared with reverse-transcription quantitative PCR (RT-qPCR) using NPS during the second pandemic wave in Switzerland. RESULTS: 402 outpatients were enrolled in a COVID-19 screening center, of whom 168 (41.8%) had a positive RT-qPCR test. The oropharyngeal Ag-RDT clinical sensitivity compared to nasopharyngeal RT-qPCR was 81% (95%CI: 74.2-86.6). Two false positives were noted out of the 234 RT-qPCR negative individuals, which resulted in a clinical specificity of 99.1% (95%CI: 96.9-99.9) for the Ag-RDT. For cycle threshold values ≤ 26.7 (≥ 1E6 SARS-CoV-2 genomes copies/mL, a presumed cut-off for infectious virus), 96.3% sensitivity (95%CI: 90.7-99.0%) was obtained with the Ag-RDT using OPS. INTERPRETATION: Based on our findings, the diagnostic performance of the Panbio™ Covid-19 RDT with OPS samples, if taken by a trained person and high requirements regarding quality of the specimen, meet the criteria required by the WHO for Ag-RDTs (sensitivity ≥80% and specificity ≥97%) in a high incidence setting in symptomatic individuals.


Assuntos
Antígenos Virais/imunologia , Teste Sorológico para COVID-19 , COVID-19 , Nasofaringe , SARS-CoV-2 , Antígenos Virais/genética , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/genética , COVID-19/imunologia , Teste de Ácido Nucleico para COVID-19 , Humanos , Nasofaringe/imunologia , Nasofaringe/virologia , Estudos Prospectivos , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Suíça/epidemiologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-33317003

RESUMO

Sanitary risk inspection protocols are often used to identify contamination hazards at water sources; however, different observers sometimes struggle to record hazards consistently. This study aimed to assess the effect of inter-observer variation in hazard observations on the strength of relationships between observed hazards and the bacterial contamination of water sources, particularly relationships with animal-related hazards. In a longitudinal study, five surveyors independently recorded hazards at 93 water sources used by 234 households in Siaya County, Kenya, in both wet and dry seasons. One surveyor collected samples from sources for subsequent Escherichia coli and intestinal enterococci testing. The relationship between each surveyor's hazard observations and high bacterial contamination was examined using logistic regression. After controlling for water source type and preceding rainfall; percentage scores for animal-related hazards were significantly related to high contamination with enterococci and E. coli for one surveyor (odds ratio 1.02; 95% confidence intervals 1.00-1.03 for both parameters), but not for the remaining four surveyors. The relationship between observed contamination hazards and the microbiological contamination of water sources is sensitive to variation in hazard recording between surveyors. Sanitary risk protocols should be designed to enable robust and consistent observation of hazards.


Assuntos
Monitoramento Ambiental , Variações Dependentes do Observador , Microbiologia da Água , Qualidade da Água , Água , Animais , Enterococcaceae/isolamento & purificação , Monitoramento Ambiental/normas , Escherichia coli/isolamento & purificação , Fezes/microbiologia , Humanos , Quênia , Estudos Longitudinais , Abastecimento de Água/normas
11.
Expo Health ; 12(4): 809-822, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195876

RESUMO

Sanitary risk inspection, an observation protocol for identifying contamination hazards around water sources, is promoted for managing rural water supply safety. However, it is unclear how far different observers consistently identify contamination hazards and consistently classify water source types using standard typologies. This study aimed to quantify inter-observer agreement in hazard identification and classification of rural water sources. Six observers separately visited 146 domestic water sources in Siaya County, Kenya, in wet and dry seasons. Each observer independently classified the source type and conducted a sanitary risk inspection using a standard protocol. Water source types assigned by an experienced observer were cross-tabulated against those of his colleagues, as were contamination hazards identified, and inter-observer agreement measures calculated. Agreement between hazards observed by the most experienced observer versus his colleagues was significant but low (intra-class correlation = 0.49), with inexperienced observers detecting fewer hazards. Inter-observer agreement in classifying water sources was strong (Cohen's kappa = 0.84). However, some source types were frequently misclassified, such as sources adapted to cope with water insecurity (e.g. tanks drawing on both piped and rainwater). Observers with limited training and experience thus struggle to consistently identify hazards using existing protocols, suggesting observation protocols require revision and their implementation should be supported by comprehensive training. Findings also indicate that field survey teams struggle to differentiate some water source types based on a standard water source classification, particularly sources adapted to cope with water insecurity. These findings demonstrate uncertainties underpinning international monitoring and analyses of safe water access via household surveys.

12.
Exp Parasitol ; 218: 107981, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32871144

RESUMO

Phlebotomine sand flies (Diptera: Psychodidae: Phlebotominae) are a group of small insects of great concern for Public Health. These dipterous are intensely studied worldwide due to their involvement in the transmission of several pathogens, mainly Leishmania spp. parasites. Nowadays, the molecular tools have been included in Phlebotomine sand flies studies and has shown to be powerful tools in bioecology studies of these dipterous. Thereby, when molecular approaches are employed, there is a great concern regarding the amount and quality of the DNA obtained for analysis. Here, seven methods of DNA extraction, between commercial kits and in house extraction protocols were evaluated. We considered measure of DNA concentration and purity ratios using a spectrophotometer to check the performance of each protocol. In addition, the quality evaluation of the DNA extracted was performed by endogenous gene PCR on samples. The results of the seven evaluated DNA extraction protocols and their implications are discussed.


Assuntos
DNA/isolamento & purificação , Psychodidae/genética , Análise de Variância , Animais , Custos e Análise de Custo , DNA/análise , DNA/normas , Eletroforese em Gel de Ágar , Feminino , Masculino , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/normas , Cloreto de Sódio , Espectrofotometria , Fatores de Tempo
13.
Int J Hyg Environ Health ; 230: 113602, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32911124

RESUMO

BACKGROUND: Emerging evidence suggests close domestic proximity of livestock and humans may lead to microbiological contamination of hands, objects, food and water supplies within domestic environments, adversely impacting public health. However, evidence quantifying the relationship between livestock, domestic animals, humans and microbiological contamination of household stored water remains limited. AIM: This longitudinal study aimed to examine the relationship between domestic contact with livestock and domestic animals on microbiological contamination of household Point-of-Use (POU) stored drinking water in rural Kenya and assess the influence of choice of faecal indicator on such associations. METHODOLOGY: A survey was performed in 234 households in Siaya county, Kenya, to observe presence of livestock (cattle, goats, poultry) and domestic animals (cats, dogs) in household compounds, alongside other risk factors for contamination of POU stored drinking water such as sanitation, storage conditions and hygiene practices. Samples from water sources (e.g. piped, spring/wells, boreholes, surface and rainwater) and from POU storage containers were tested for E. coli and intestinal enterococci. Livestock-related risk factors for water contamination were examined through multinomial regression, controlling for confounders. RESULTS: Rainwater was the main POU water source and was found to be highly susceptible to contamination. Multivariate analysis showed greater risk of gross (>100 CFU/100 mL) water contamination (with E. coli) for households where goats were observed, and/or where poultry roosted in proximity to stored household water (relative risk RR = 2.71; p = 0.001 and RR = 2.02; p = 0.012 respectively). Presence of a poultry coop was also associated with elevated intestinal enterococci densities (RR = 4.46; p = 0.001). Associations between contamination and livestock risk factors were thus similar for both bacteria groups, but E. coli counts declined more rapidly following collection from surface waters than enterococci counts (p = 0.024). CONCLUSION: The presence of livestock (particularly goats) and poultry within household compounds increases POU water contamination risk, suggesting the need for improved interventions to address cross-contamination within rural domestic settings. Within Siaya county, more effective community education is needed to raise awareness of POU water quality protection, particularly of rainwater.


Assuntos
Água Potável , Gado , Animais , Gatos , Bovinos , Cães , Escherichia coli , Humanos , Quênia , Estudos Longitudinais , Microbiologia da Água , Qualidade da Água , Abastecimento de Água
14.
Trop Anim Health Prod ; 52(2): 625-635, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31471879

RESUMO

Carcass characteristic and meat quality from bulls and Nellore steers (n = 64 total) subjected to different grazing heights (15, 25, 35, and 45 cm) were evaluated isolatedly, under continuous grazing and variable load, in pastures of Convert grass. The experimental period was from May 2015 to June 2017, in an area of 16 ha, divided into 16 paddocks of 1 ha. The experimental design was randomized blocks with four replications. Each paddock was grazed by three animals and regulators, used to adjust grazing heights. The final slaughter weight, hot carcass, and crude protein in the meat of steers were higher when the pastures were managed at 42 cm. When the pasture was managed between 25 and 35 cm in height, greater fat thickness, marbling, muscle:bone and muscle+fat:bone ratio and lower color* of the meat and percentage of bone were found. For the steers, the height of 40 cm provided higher fat thickness and marbling in the meat. The loss during thawing in meat was greater at 28 cm in height. The heights of grazing alter the carcass characteristics and meat of bulls and steers.


Assuntos
Criação de Animais Domésticos/métodos , Bovinos/fisiologia , Carne/análise , Poaceae/crescimento & desenvolvimento , Animais , Brasil , Masculino , Distribuição Aleatória
15.
J Minim Invasive Gynecol ; 26(3): 558-563, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30165187

RESUMO

Gynecologic surgery is associated with various perioperative complications, especially urinary tract injuries. Intraoperative cystoscopy plays an important role in allowing assessment of the bladder to ensure the absence of injuries. Verification of the urinary jets from the ureters is a fundamental step that is not always easy to accomplish. Dyes are frequently used, but these are not always available and are associated with adverse effects. The present study aimed to demonstrate the use of CO2 as a medium for distension during cystoscopy. A total of 47 patients underwent CO2 cystoscopy after laparoscopic hysterectomy (n = 26) or bladder endometriosis nodule resection (n = 21). In all patients, the ureteral jets were readily identified, leaving no doubt as to their patency. The median interval between the onset of cystoscopy and the view of jetting from both ureteral ostia was 145 seconds (range, 80-300 seconds). All cystoscopies were normal, and no patient had any signs of accidental urinary tract injury in the follow-up period. Two patients experienced mild urinary tract infection. This cystoscopy technique using CO2 is fast, easy, safe, and efficient. We recommend bladder distension with CO2 as a reasonable alternative technique when cystoscopy is required during gynecologic procedures.


Assuntos
Dióxido de Carbono , Cistoscopia , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Complicações Intraoperatórias/diagnóstico , Ureter/lesões , Obstrução Ureteral/diagnóstico , Bexiga Urinária/lesões , Adulto , Feminino , Humanos , Complicações Intraoperatórias/etiologia , Pessoa de Meia-Idade , Resultado do Tratamento , Obstrução Ureteral/etiologia
16.
Sensors (Basel) ; 18(12)2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30558278

RESUMO

In this study, we developed an online graphical and intuitive interface connected to a server aiming to facilitate professional access worldwide to those facing problems with bovine blastocysts classification. The interface Blasto3Q, where 3Q refers to the three qualities of the blastocyst grading, contains a description of 24 variables that were extracted from the image of the blastocyst and analyzed by three Artificial Neural Networks (ANNs) that classify the same loaded image. The same embryo (i.e., the biological specimen) was submitted to digital image capture by the control group (inverted microscope with 40× magnification) and the experimental group (stereomicroscope with maximum of magnification plus 4× zoom from the cell phone camera). The images obtained from the control and experimental groups were uploaded on Blasto3Q. Each image from both sources was evaluated for segmentation and submitted (only if it could be properly or partially segmented) for automatic quality grade classification by the three ANNs of the Blasto3Q program. Adjustments on the software program through the use of scaling algorithm software were performed to ensure the proper search and segmentation of the embryo in the raw images when they were captured by the smartphone, since this source produced small embryo images compared with those from the inverted microscope. With this new program, 77.8% of the images from smartphones were successfully segmented and from those, 85.7% were evaluated by the Blasto3Q in agreement with the control group.


Assuntos
Inteligência Artificial , Smartphone , Software , Algoritmos , Animais , Blastocisto/citologia , Bovinos , Redes Neurais de Computação
17.
PLoS One ; 13(7): e0201344, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30048542

RESUMO

Ebola and cholera treatment centres (ETC and CTC) generate considerable quantities of excreta that can further the transmission of disease amongst patients and health workers. Therefore, approaches for the safe handling, containment and removal of excreta within such settings are needed to minimise the likelihood of onward disease transmission. This study compared the performance and suitability of three chlorine-based approaches (0.5% HTH, NaDCC and NaOCl (domestic bleach)) and three lime-based approaches (10%, 20% and 30% Ca(OH)2). The experiments followed recent recommendations for Ebola Treatment Centres. Three excreta matrices containing either raw municipal wastewater, or raw municipal wastewater plus 10% or 20% (w/v) added faecal sludge, were treated in 14 litre buckets at a ratio of 1:10 (chlorine solutions or lime suspensions: excreta matrix). The effects of mixing versus non-mixing and increasing contact time (10 and 30 mins) were also investigated. Bacterial (faecal coliforms (FC) and intestinal enterococci (IE)) and viral (somatic coliphages (SOMPH), F+specific phages (F+PH) and Bacteroides fragilis phages (GB-124PH)) indicators were used to determine the efficacy of each approach. Lime-based approaches provided greater treatment efficacy than chlorine-based approaches, with lime (30% w/v) demonstrating the greatest efficacy (log reductions values, FC = 4.75, IE = 4.16, SOMPH = 2.85, F+PH = 5.13 and GB124PH = 5.41). There was no statistical difference in efficacy between any of the chlorine-based approaches, and the highest log reduction values were: FC = 2.90, IE = 2.36, SOMPH = 3.01, F+PH = 2.36 and GB124PH = 0.74. No statistical difference was observed with respect to contact time for any of the approaches, and no statistical differences were observed with respect to mixing for the chlorine-based approaches. However, statistically significant increases in the efficacy of some lime-based approaches were observed following mixing. These findings provide evidence and practical advice to inform safe handling and containment of excreta and ensure more effective health protection in future emergency settings.


Assuntos
Desinfetantes/química , Desinfecção/métodos , Fezes/microbiologia , Compostos de Cálcio/química , Cloro/química , Cólera/microbiologia , Cólera/prevenção & controle , Halogenação , Doença pelo Vírus Ebola/microbiologia , Doença pelo Vírus Ebola/prevenção & controle , Humanos , Óxidos/química , Esgotos/microbiologia , Hipoclorito de Sódio/química , Águas Residuárias/microbiologia , Microbiologia da Água
19.
J Cell Biol ; 216(8): 2283-2293, 2017 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-28696227

RESUMO

A primary function of 5' regions in many secretory protein mRNAs is to encode an endoplasmic reticulum (ER) targeting sequence. In this study, we show how the regions coding for the ER-targeting sequences of the influenza glycoproteins NA and HA also function as translational regulatory elements that are controlled by the viral RNA-binding protein (RBP) NS1. The translational increase depends on the nucleotide composition and 5' positioning of the ER-targeting sequence coding regions and is facilitated by the RNA-binding domain of NS1, which can associate with ER membranes. Inserting the ER-targeting sequence coding region of NA into different 5' UTRs confirmed that NS1 can promote the translation of secretory protein mRNAs based on the nucleotides within this region rather than the resulting amino acids. By analyzing human protein mRNA sequences, we found evidence that this mechanism of using 5' coding regions and particular RBPs to achieve gene-specific regulation may extend to human-secreted proteins.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/biossíntese , Vírus da Influenza A Subtipo H1N1/enzimologia , Neuraminidase/metabolismo , RNA Mensageiro/metabolismo , RNA Viral/metabolismo , Proteínas não Estruturais Virais/metabolismo , Proteínas Virais/metabolismo , Regiões 3' não Traduzidas , Regiões 5' não Traduzidas , Células A549 , Animais , Sítios de Ligação , Células COS , Chlorocebus aethiops , Retículo Endoplasmático/enzimologia , Células HEK293 , Células HeLa , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Neuraminidase/genética , Ligação Proteica , Biossíntese de Proteínas , Domínios Proteicos , RNA Mensageiro/genética , RNA Viral/genética , Partícula de Reconhecimento de Sinal/genética , Partícula de Reconhecimento de Sinal/metabolismo , Transfecção , Células Vero , Proteínas não Estruturais Virais/genética , Proteínas Virais/genética
20.
Nature ; 526(7572): 273-276, 2015 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-26416749

RESUMO

Super-enhancers (SEs), which are composed of large clusters of enhancers densely loaded with the Mediator complex, transcription factors and chromatin regulators, drive high expression of genes implicated in cell identity and disease, such as lineage-controlling transcription factors and oncogenes. BRD4 and CDK7 are positive regulators of SE-mediated transcription. By contrast, negative regulators of SE-associated genes have not been well described. Here we show that the Mediator-associated kinases cyclin-dependent kinase 8 (CDK8) and CDK19 restrain increased activation of key SE-associated genes in acute myeloid leukaemia (AML) cells. We report that the natural product cortistatin A (CA) selectively inhibits Mediator kinases, has anti-leukaemic activity in vitro and in vivo, and disproportionately induces upregulation of SE-associated genes in CA-sensitive AML cell lines but not in CA-insensitive cell lines. In AML cells, CA upregulated SE-associated genes with tumour suppressor and lineage-controlling functions, including the transcription factors CEBPA, IRF8, IRF1 and ETV6 (refs 6-8). The BRD4 inhibitor I-BET151 downregulated these SE-associated genes, yet also has anti-leukaemic activity. Individually increasing or decreasing the expression of these transcription factors suppressed AML cell growth, providing evidence that leukaemia cells are sensitive to the dosage of SE-associated genes. Our results demonstrate that Mediator kinases can negatively regulate SE-associated gene expression in specific cell types, and can be pharmacologically targeted as a therapeutic approach to AML.


Assuntos
Quinase 8 Dependente de Ciclina/antagonistas & inibidores , Quinases Ciclina-Dependentes/antagonistas & inibidores , Elementos Facilitadores Genéticos/genética , Regulação Neoplásica da Expressão Gênica/genética , Genes Neoplásicos/genética , Leucemia Mieloide Aguda/enzimologia , Leucemia Mieloide Aguda/genética , Animais , Proteínas de Ciclo Celular , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Linhagem da Célula/efeitos dos fármacos , Linhagem da Célula/genética , Quinase 8 Dependente de Ciclina/metabolismo , Quinases Ciclina-Dependentes/metabolismo , Progressão da Doença , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes Supressores de Tumor/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Masculino , Camundongos , Camundongos Endogâmicos , Camundongos SCID , Proteínas Nucleares/antagonistas & inibidores , Compostos Policíclicos/farmacologia , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
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