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1.
Braz. j. biol ; 83: e253009, 2023. tab, graf
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1339373

RESUMO

Abstract Today, global focus of research is to explore the solution of energy crisis and environmental pollution. Like other agricultural countries, bulk quantities of watermelon peels (WMP) are disposed-off in environment as waste in Pakistan and appropriate management of this waste is the need of hour to save environment from pollution. The work emphasizes the role of ethanologenic yeasts to utilize significant sugars present in WMP for low-cost bioethanol fermentation. Dilute hydrochloric acid hydrolysis of WMP was carried out on optimized conditions employing RSM (response surface methodology) following central composite design (CCD). This experimental design is based on optimization of ethanologenesis involving some key independent parameters such as WMP hydrolysate and synthetic media ratio (X1), incubation temperature (X2) and incubation temperature (X3) for maximal ethanol yield exploiting standard (Saccharomyces cerevisiae K7) as well as experimental (Metchnikowia cibodasensisY34) yeasts. The results revealed that maximal ethanol yields obtained from S. cerevisiae K7 was 0.36±0.02 g/g of reducing sugars whereas M. cibodasensisY34, yielded 0.40±0.01 g ethanol/g of reducing sugars. The yeast isolate M. cibodasensisY34 appeared as promising ethanologen and embodies prospective potential for fermentative valorization of WMP-to-bioethanol.


Resumo Hoje, o foco global da pesquisa é explorar a solução da crise energética e da poluição ambiental. Como em outros países agrícolas, grandes quantidades de cascas de melancia (WMP) são descartadas como resíduos no meio ambiente no Paquistão, mas a gestão adequada desses resíduos é a mais recente solução para salvar o meio ambiente da poluição. O trabalho enfatiza o papel das leveduras etanologênicas para utilizar açúcares significativos presentes no WMP para fermentação de bioetanol de baixo custo. A hidrólise de ácido clorídrico diluído de WMP foi realizada em condições otimizadas empregando RSM (metodologia de superfície de resposta) e seguindo o projeto de composto central (CCD). Este projeto experimental é baseado na otimização da etanologenesis envolvendo alguns parâmetros independentes importantes, como hidrolisado de WMP e razão de meio sintético (X1), temperatura de incubação (X2) e temperatura de incubação (X3) para rendimento máximo de etanol explorando o padrão (Saccharomyces cerevisiae K7) também como leveduras experimentais (Metchnikowia cibodasensis Y34). Os resultados revelaram que os rendimentos máximos de etanol obtidos a partir de S. cerevisiae K7 foi de 0,36 ± 0,02 g / g de açúcares redutores, enquanto M. cibodasensis Y34 rendeu 0,40 ± 0,01 g de etanol / g de açúcares redutores. O isolado de levedura M. cibodasensis Y34 apareceu como um etanologeno promissor e incorpora um potencial prospectivo para a valorização fermentativa de WMP em bioetanol.

2.
Braz. j. biol ; 82: e239991, 2022. tab, graf
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1278503

RESUMO

Abstract High resistance to antimicrobials is associated with biofilm formation responsible for infectious microbes to withstand severe conditions. Therefore, new alternatives are necessary as biofilm inhibitors to control infections. In this study, the antimicrobial and antibiofilm activities of Fagonia indica extracts were evaluated against MDR clinical isolates. The extract exhibited its antibiofilm effect by altering adherence and disintegration of bacterial cell wall. Fagonia indica has antibacterial effect as minimum inhibitory concentration (MIC) values ranging from 125 to 500 µg mL-1 and minimum bactericidal concentration (MBC) value was 500-3000 µg mL-1 against multidrug resistant (MDR) clinical isolates. The extract exhibited its antibiofilm effect by altering adherence and disintegration of bacterial cell wall. Fagonia indica had antibacterial effect as minimum inhibitory concentration (MIC) values ranging from 125 to 500 µg mL-1 and minimum bactericidal concentration (MBC) value was 500-3000 µg mL-1 against MDR isolates. The maximum inhibitory effects of Fagonia indica chloroform extract on biofilm formation was observed on Staphylococcus aureus (71.84%) followed by Klebsiella pneumoniae (70.83%) after 48 hrs showing that inhibition is also time dependent. Our results about bacterial cell protein leakage indicated that MDR isolates treated with chloroform extract of Fagonia indica showed maximum protein leakage of K. pneumoniae (59.14 µg mL-1) followed by S. aureus (56.7 µg mL-1). Cell attachment assays indicated that chloroform extract resulted in a 43.5-53.5% inhibition of cell adherence to a polystyrene surface. Our results revealed that extracts of Fagonia indica significantly inhibited biofilm formation among MDR clinical isolates, therefore, could be applied as antimicrobial agents and cost effective biofilm inhibitor against these MDR isolates.


Resumo A alta resistência aos antimicrobianos está associada à formação de biofilme responsável por micróbios infecciosos para suportar condições severas. Portanto, novas alternativas são necessárias como inibidores de biofilme para controlar infecções. Neste estudo, as atividades antimicrobiana e antibiofilme dos extratos de Fagonia indica foram avaliadas contra isolados clínicos MDR. O extrato exibiu seu efeito antibiofilme ao alterar a aderência e a desintegração da parede celular bacteriana. Fagonia indica tem efeito antibacteriano com valores de concentração inibitória mínima (CIM) variando de 125 a 500 µg mL-1, e valor de concentração bactericida mínima (MBC) de 500-3000 µg mL-1 contra isolados clínicos multirresistentes (MDR). O extrato exibiu seu efeito antibiofilme ao alterar a aderência e a desintegração da parede celular bacteriana. Fagonia indica teve efeito antibacteriano com valores de concentração inibitória mínima (CIM) variando de 125 a 500 µg mL-1, e concentração bactericida mínima (MBC) de 500-3000 µg mL-1 contra isolados MDR. Os efeitos inibitórios máximos do extrato de clorofórmio Fagonia indica na formação de biofilme foi observada em Staphylococcus aureus (71,84%), seguido por Klebsiella pneumoniae (70,83%) após 48 horas, mostrando que a inibição também é dependente do tempo. Nossos resultados sobre extravasamento de proteínas de células bacterianas indicaram que isolados MDR tratados com extrato clorofórmico de Fagonia indica apresentaram vazamento máximo de proteínas de K. pneumoniae (59,14 µg mL-1), seguido por S. aureus (56,7 µg mL-1). Ensaios de fixação de células indicaram que o extrato de clorofórmio resultou em uma inibição de 43,5-53,5% da aderência das células a uma superfície de poliestireno. Nossos resultados revelaram que extratos de Fagonia indica inibiram significativamente a formação de biofilme entre isolados clínicos MDR, portanto, poderiam ser aplicados como agentes antimicrobianos e inibidores de biofilme de baixo custo contra esses isolados MDR.

3.
Public Health ; 202: 58-64, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34894534

RESUMO

OBJECTIVES: There is growing evidence of an association between social participation and improved physical and mental health among older individuals. The aims of this study were to explore the relationship between self-reported participation in groups, clubs, or organizations and all-cause mortality among older adults and examine the role of physical activity as a potential modifier of the health effects of social participation. STUDY DESIGN: EPIC-Norfolk is a prospective cohort study that recruited 25,639 individuals between the ages of 40 and 79 in Norfolk County, England. This study involved a retrospective analysis of 8623 participants who had returned for the third health check between 2004 and 2011. METHODS: Participants were categorized into those who reported participating socially and those who did not and were stratified by involvement in 0, 1, or 2 or more groups. Cox Proportional Hazards models were constructed to compare all-cause mortality between the groups. Stratum-specific hazard ratios were calculated by physical activity level to assess for effect modification. RESULTS: Of the participants, 861 (9.98%) died during the follow-up period. After adjustment for confounding, social participation was associated with lower all-cause mortality (HR 0.84, 95% CI 0.73-0.97). Involvement in 2 or more groups was associated with lower all-cause mortality (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.70-0.97), but the association was not statistically significant for people involved in only 1 group (HR 0.86, 95% CI 0.73-1.03). Physical activity appeared to modify the effect of social participation on mortality. CONCLUSIONS: This study's findings provide evidence of an association between social participation and lower all-cause mortality for older adults. They also suggest that the effect of social participation on health is greater for people who are more physically active. Population-level interventions to facilitate social participation may contribute to improving health and wellbeing among older individuals.

4.
Curr Rheumatol Rev ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34620059

RESUMO

The Kuwait Association of Rheumatology members met three times in April 2020 to quickly address and support the local practitioners treating rheumatic disease in Kuwait and the Gulf region during the COVID-19 pandemic. As patients with rheumatic and musculoskeletal disease (RMD) may need modifications to their therapy during the COVID-19 pandemic, we voted online for general guidance that local practitioners needed. In this review, we have addressed the vulnerability of rheumatic patients and issues surrounding their optimum management. We base our recommendations on a synthesis of national/international guidelines and expert consensus among KAR members in the context of the Kuwaiti healthcare system caring for the patient population with RMD. The most recent reports from the World Health Organization, the Center for Disease Control, the National Institutes of Health - National Medical Library, and the COVID-19 educational website of the United Kingdom National Health Service have been incorporated. We discuss the management of RMD in various clinical scenarios: screening protocols in an infusion clinic, medication protocols for stable patients and care for suspected or confirmed COVID infection and whether they are stable, in a disease flare or newly diagnosed. Besides, we also outline the conditions for the hospital admission. This guidance is for the specialist and non-specialist readership and should be regarded as interim as the virus is relatively new and we rely on experience and necessity more than evidence collection. The guidance presented should be supplemented with recent scientific evidence wherever applicable.

6.
Braz J Biol ; 83: e253009, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34495170

RESUMO

Today, global focus of research is to explore the solution of energy crisis and environmental pollution. Like other agricultural countries, bulk quantities of watermelon peels (WMP) are disposed-off in environment as waste in Pakistan and appropriate management of this waste is the need of hour to save environment from pollution. The work emphasizes the role of ethanologenic yeasts to utilize significant sugars present in WMP for low-cost bioethanol fermentation. Dilute hydrochloric acid hydrolysis of WMP was carried out on optimized conditions employing RSM (response surface methodology) following central composite design (CCD). This experimental design is based on optimization of ethanologenesis involving some key independent parameters such as WMP hydrolysate and synthetic media ratio (X1), incubation temperature (X2) and incubation temperature (X3) for maximal ethanol yield exploiting standard (Saccharomyces cerevisiae K7) as well as experimental (Metchnikowia cibodasensisY34) yeasts. The results revealed that maximal ethanol yields obtained from S. cerevisiae K7 was 0.36±0.02 g/g of reducing sugars whereas M. cibodasensisY34, yielded 0.40±0.01 g ethanol/g of reducing sugars. The yeast isolate M. cibodasensisY34 appeared as promising ethanologen and embodies prospective potential for fermentative valorization of WMP-to-bioethanol.


Assuntos
Cucurbitaceae , Etanol , Biotransformação , Fermentação , Estudos Prospectivos , Saccharomyces cerevisiae , Água
7.
Carbohydr Polym ; 269: 118346, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34294353

RESUMO

In the present study, the novel Ag/cellulose nanocrystal (CNC)-doped CeO2 quantum dots (QDs) with highly efficient catalytic performance were synthesized using one pot co-precipitation technique, which were then applied in the degradation of methylene blue and ciprofloxacin (MBCF) in wastewater. Catalytic activity against MBCF dye was significantly reduced (99.3%) for (4%) Ag dopant concentration in acidic medium. For Ag/CNC-doped CeO2 vast inhibition domain of G-ve was significantly confirmed as (5.25-11.70 mm) and (7.15-13.60 mm), while medium- to high-concentration of CNC levels were calculated for G + ve (0.95 nm, 1.65 mm), respectively. Overall, (4%) Ag/CNC-doped CeO2 revealed significant antimicrobial activity against G-ve relative to G + ve at both concentrations, respectively. Furthermore, in silico molecular docking studies were performed against selected enzyme targets dihydrofolate reductase (DHFR), dihydropteroate synthase (DHPS), and DNA gyrase belonging to folate and nucleic acid biosynthetic pathway, respectively to rationalize possible mechanism behind bactericidal potential of CNC-CeO2 and Ag/CNC-CeO2.


Assuntos
Antibacterianos/farmacologia , Celulose/química , Cério/química , Corantes/química , Pontos Quânticos/química , Prata/farmacologia , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/efeitos da radiação , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Catálise/efeitos da radiação , Celulose/síntese química , Celulose/metabolismo , Celulose/efeitos da radiação , Cério/metabolismo , Cério/efeitos da radiação , Ciprofloxacina/química , DNA Girase/química , DNA Girase/metabolismo , Di-Hidropteroato Sintase/química , Di-Hidropteroato Sintase/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Luz , Azul de Metileno/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Ligação Proteica , Pontos Quânticos/metabolismo , Pontos Quânticos/efeitos da radiação , Prata/química , Prata/metabolismo , Prata/efeitos da radiação , Staphylococcus aureus/efeitos dos fármacos , Tetra-Hidrofolato Desidrogenase/química , Tetra-Hidrofolato Desidrogenase/metabolismo , Poluentes Químicos da Água/química , Purificação da Água/métodos
8.
Epidemiol Infect ; 149: e193, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34210371

RESUMO

There is a paucity of evidence about the prevalence and risk factors for symptomatic infection among children. This study aimed to describe the prevalence of symptomatic coronavirus disease 2019 (COVID-19) and its risk factors in children and adolescents aged 0-18 years in Qatar. We conducted a cross-sectional study of all children aged 0-18 years diagnosed with COVID-19 using polymerase chain reaction in Qatar during the period 1st March to 31st July 2020. A generalised linear model with a binomial family and identity link was used to assess the association between selected factors and the prevalence of symptomatic infection. A total of 11 445 children with a median age of 8 years (interquartile range (IQR) 3-13 years) were included in this study. The prevalence of symptomatic COVID-19 was 36.6% (95% confidence interval (CI) 35.7-37.5), and it was similar between children aged <5 years (37.8%), 5-9 years (34.3%) and 10 + years (37.3%). The most frequently reported symptoms among the symptomatic group were fever (73.5%), cough (34.8%), headache (23.2%) and sore throat (23.2%). Fever (82.8%) was more common in symptomatic children aged <5 years, while cough (38.7%) was more prevalent in those aged 10 years or older, compared to other age groups. Variables associated with an increased risk of symptomatic infection were; contact with confirmed cases (RD 0.21; 95% CI 0.20-0.23; P = 0.001), having visited a health care facility (RD 0.54; 95% CI 0.45-0.62; P = 0.001), and children aged under 5 years (RD 0.05; 95% CI 0.02-0.07; P = 0.001) or aged 10 years or older (RD 0.04; 95% CI 0.02-0.06; P = 0.001). A third of the children with COVID-19 were symptomatic with a higher proportion of fever in very young children and a higher proportion of cough in those between 10 and 18 years of age.


Assuntos
COVID-19/epidemiologia , Tosse/epidemiologia , Febre/epidemiologia , Cefaleia/epidemiologia , Faringite/epidemiologia , Adolescente , COVID-19/virologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Catar/epidemiologia , Fatores de Risco
9.
Braz J Biol ; 82: e239991, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34190801

RESUMO

High resistance to antimicrobials is associated with biofilm formation responsible for infectious microbes to withstand severe conditions. Therefore, new alternatives are necessary as biofilm inhibitors to control infections. In this study, the antimicrobial and antibiofilm activities of Fagonia indica extracts were evaluated against MDR clinical isolates. The extract exhibited its antibiofilm effect by altering adherence and disintegration of bacterial cell wall. Fagonia indica has antibacterial effect as minimum inhibitory concentration (MIC) values ranging from 125 to 500 µg mL-1 and minimum bactericidal concentration (MBC) value was 500-3000 µg mL-1 against multidrug resistant (MDR) clinical isolates. The extract exhibited its antibiofilm effect by altering adherence and disintegration of bacterial cell wall. Fagonia indica had antibacterial effect as minimum inhibitory concentration (MIC) values ranging from 125 to 500 µg mL-1 and minimum bactericidal concentration (MBC) value was 500-3000 µg mL-1 against MDR isolates. The maximum inhibitory effects of Fagonia indica chloroform extract on biofilm formation was observed on Staphylococcus aureus (71.84%) followed by Klebsiella pneumoniae (70.83%) after 48 hrs showing that inhibition is also time dependent. Our results about bacterial cell protein leakage indicated that MDR isolates treated with chloroform extract of Fagonia indica showed maximum protein leakage of K. pneumoniae (59.14 µg mL-1) followed by S. aureus (56.7 µg mL-1). Cell attachment assays indicated that chloroform extract resulted in a 43.5-53.5% inhibition of cell adherence to a polystyrene surface. Our results revealed that extracts of Fagonia indica significantly inhibited biofilm formation among MDR clinical isolates, therefore, could be applied as antimicrobial agents and cost effective biofilm inhibitor against these MDR isolates.


Assuntos
Extratos Vegetais , Staphylococcus aureus , Bactérias , Biofilmes , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia
10.
Nanoscale Res Lett ; 16(1): 56, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33825981

RESUMO

Various concentrations (0.01, 0.03 and 0.05 wt ratios) of graphene oxide (GO) nanosheets were doped into magnesium oxide (MgO) nanostructures using chemical precipitation technique. The objective was to study the effect of GO dopant concentrations on the catalytic and antibacterial behavior of fixed amount of MgO. XRD technique revealed cubic phase of MgO, while its crystalline nature was confirmed through SAED profiles. Functional groups presence and Mg-O (443 cm-1) in fingerprint region was evident with FTIR spectroscopy. Optical properties were recorded via UV-visible spectroscopy with redshift pointing to a decrease in band gap energy from 5.0 to 4.8 eV upon doping. Electron-hole recombination behavior was examined through photoluminescence (PL) spectroscopy. Raman spectra exhibited D band (1338 cm-1) and G band (1598 cm-1) evident to GO doping. Formation of nanostructure with cubic and hexagon morphology was confirmed with TEM, whereas interlayer average d-spacing of 0.23 nm was assessed using HR-TEM. Dopants existence and evaluation of elemental constitution Mg, O were corroborated using EDS technique. Catalytic activity against methyl blue ciprofloxacin (MBCF) was significantly reduced (45%) for higher GO dopant concentration (0.05), whereas bactericidal activity of MgO against E. coli was improved significantly (4.85 mm inhibition zone) upon doping with higher concentration (0.05) of GO, owing to the formation of nanorods.

11.
Auton Neurosci ; 233: 102808, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33901811

RESUMO

POTS is under diagnosed with an estimated prevalence of 0.2%. North American and Australian researchers, as well as patient groups have called for more research into POTS. However, there has been no comprehensive appraisal of the current POTS evidence base. AIM: To map the POTS evidence base. METHODS: Two reviewers systematically searched 12 databases until July 1st 2019 using the search term "Postural Tachycardia Syndrome" (n = 7280) and categorised the literature. Inclusion criteria included all adult published literature with no language restrictions. 779 papers are analysed and mapped. RESULTS: Seven themes were identified: symptomology and quality of life 16.8% (n = 132), biomedical topics 16.5% (n = 130), co-morbidities 10.3% (n = 81), non-pharmacological management 9.8% (n = 77), aetiologies 6.9% (n = 53), pharmacological management 6.7% (n = 53), and clinical management 6.6% (n = 52). There 45 subthemes. Quality appraisal of the research studies (n = 233) evaluated design, sample size, outcome measures, data analysis and research biases. 74.8% (n = 175) were observational designs and 25.2% (n = 59) were experimental designs (16 using a randomised controlled design, 11 of which had a sample size greater than 21). 47.4% (n = 111) of studies only measured duration of effect for <1 day. 11.5% (n = 27) of studies reported outcomes using an unvalidated subjective measurement tool. CONCLUSION: The volume of adult POTS literature is small and the validity and reliability of the research lacks rigour. The evidence map methodology provides POTS researchers with a benchmark for research thus far. This paper adds an in-depth research appraisal to the broad calls for action, highlighting the pressing need for multicentre, good quality research in POTS, to support guidelines and consensus development in the future.


Assuntos
Síndrome da Taquicardia Postural Ortostática , Adulto , Austrália , Comorbidade , Humanos , Síndrome da Taquicardia Postural Ortostática/epidemiologia , Síndrome da Taquicardia Postural Ortostática/terapia , Qualidade de Vida , Reprodutibilidade dos Testes
12.
CRISPR J ; 3(3): 177-187, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32584143

RESUMO

Multiplexed genome editing with DNA endonucleases has broad application, including for cellular therapies, but chromosomal translocations, natural byproducts of inducing simultaneous genomic breaks, have not been explored in detail. Here we apply various CRISPR-Cas nucleases to edit the T cell receptor alpha and beta 2 microglobulin genes in human primary T cells and comprehensively evaluate the frequency and stability of the resulting translocations. A thorough translocation frequency analysis using three orthogonal methods (droplet digital PCR, unidirectional sequencing, and metaphase fluorescence in situ hybridization) yielded comparable results and an overall translocation rate of ∼7% between two simultaneous CRISPR-Cas9 induced edits. In addition, we show that chromosomal translocations can be reduced when using different nuclease combinations, or by the presence of a homologous single stranded oligo donor for multiplexed genome editing. Importantly, the two different approaches for translocation reduction are compatible with cell therapy applications.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes/métodos , Linfócitos T , Translocação Genética , Linfócitos T CD4-Positivos , Proteína 9 Associada à CRISPR/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , DNA/genética , Endonucleases/genética , Genoma Humano , Humanos , Hibridização in Situ Fluorescente , Herança Multifatorial , RNA Guia , Streptococcus pyogenes
13.
Pathogens ; 8(2)2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31117254

RESUMO

Background: Expatriates represent >80% of Qatar's population, mostly arriving from countries in Africa and Asia that are endemic with many diseases. This increases the risk for introducing new pathogens into the country and provides a platform for maintenance of endemic pathogen circulation. Here, we report on the incidence and epidemiological characteristics of hepatitis B in Qatar between 2010 and 2014. Methods: We performed a retrospective epidemiological data analysis using the data available at the surveillance system of the Ministry of Public Health (MOPH) in Qatar. Data were collected from distinctive public and private incorporates around the nation. Reported cases of hepatitis B patients represent those who met the stringent case definition as per World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) guidelines and eventually reported to MOPH. Results: The annual incidence rates of hepatitis B cases were 30.0, 34.2, 30.5, 39.4, and 19.8 per 100,000 population in 2010, 2011, 2012, 2013, and 2014, respectively. There was no specific trend or seasonality for the reported cases. The incidence rates were higher in females compared to males between 2010 and 2012, but similar in 2013 and 2014. The highest incidence rates were reported among individuals between 25 and 34 years of age. No cases were reported in children younger than five years in 2013 and 2014. Rates of hepatitis B cases declined dramatically in 2014, in both Qataris and non-Qataris, as compared to the previous years. Conclusion: Our results indicate a dramatic decline of hepatitis B cases in Qatar but mandate improved surveillance and vaccination efforts in expatriates in the nation.

14.
Pharmgenomics Pers Med ; 12: 47-57, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31114289

RESUMO

Purpose: Variability in response to warfarin is one of the main obstacles challenging its use in clinical practice. Vitamin K epoxide reductase complex (VKORC) is the target enzyme of warfarin, and variations in the form of single nucleotide polymorphisms (SNPs) in VKORC1, coding for this enzyme, are known to cause resistance to warfarin treatment. This study aimed to explore VKORC1 variants in Emirati patients receiving warfarin treatment and to correlate their genotypes at the studied SNPs to their maintenance warfarin dose. Patients and methods: Sanger sequencing of the majority of the VKORC1 gene was applied to samples from 90 patients and 117 normal individuals recruited from Tawam Hospital, Al-Ain, UAE. Genotypes at the following variants were determined (rs9923231, rs188009042, rs61742245, rs17708472, rs9934438, rs8050894, rs2359612, rs7294). Statistical analysis was applied, including ANOVA, cross-tabulation, and multiple linear regression analysis, to determine the ability of nongenetic factors (age and gender) and genetic factors (VKORC1 genotypes) to explain variability in warfarin dose in patients. Results: Different frequencies of minor alleles were detected in the selected SNPs. Significant variation among genotypes at six VKORC1 variants were identified (rs9923231, rs9934438, rs8050894, rs2359612, rs7294). The main predictors for warfarin dose were rs9923231, age, and rs61742245 with 50.7% of the average warfarin dose in our sample could be explained by a regression model built on these three factors. Conclusion: This is the first report of the explanatory power of VKORC1 genotypes and nongenetic factors (age and gender) on warfarin dose among Emiratis. Also, this study highlighted the positive effect of considering rare pharmacogenomic variants on explaining warfarin dose variability.

15.
J Neuroinflammation ; 15(1): 166, 2018 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-29807534

RESUMO

BACKGROUND: A wealth of evidence implicates both central and peripheral immune changes as contributing to the pathogenesis of Parkinson's disease (PD). It is critical to better understand this aspect of PD given that it is a tractable target for disease-modifying therapy. Age-related changes are known to occur in the immune system (immunosenescence) and might be of particular relevance in PD given that its prevalence rises with increasing age. We therefore sought to investigate this with respect to T cell replicative senescence, a key immune component of human ageing. METHODS: Peripheral blood mononuclear cells were extracted from blood samples from 41 patients with mild PD (Hoehn and Yahr stages 1-2, mean (SD) disease duration 4.3 (1.2) years) and 41 age- and gender-matched controls. Immunophenotyping was performed with flow cytometry using markers of T lymphocyte activation and senescence (CD3, CD4, CD8, HLA-DR, CD38, CD28, CCR7, CD45RA, CD57, CD31). Cytomegalovirus (CMV) serology was measured given its proposed relevance in driving T cell senescence. RESULTS: Markers of replicative senescence in the CD8+ population were strikingly reduced in PD cases versus controls (reduced CD57 expression (p = 0.005), reduced percentage of 'late differentiated' CD57loCD28hi cells (p = 0.007) and 'TEMRA' cells (p = 0.042)), whilst expression of activation markers (CD28) was increased (p = 0.005). This was not driven by differences in CMV seropositivity. No significant changes were observed in the CD4 population. CONCLUSIONS: This study demonstrates for the first time that the peripheral immune profile in PD is distinctly atypical for an older population, with a lack of the CD8+ T cell replicative senescence which characterises normal ageing. This suggests that 'abnormal' immune ageing may contribute to the development of PD, and markers of T cell senescence warrant further investigation as potential biomarkers in this condition.


Assuntos
Envelhecimento/patologia , Imunossenescência , Doença de Parkinson/patologia , Linfócitos T/metabolismo , Idoso , Antígenos CD/metabolismo , Estudos de Casos e Controles , Senescência Celular , Citomegalovirus/imunologia , Feminino , Citometria de Fluxo , Humanos , Imunoglobulina G , Imunofenotipagem , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/sangue , Sorologia
16.
BMC Genomics ; 19(1): 212, 2018 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-29562890

RESUMO

BACKGROUND: Understanding the diversity of repair outcomes after introducing a genomic cut is essential for realizing the therapeutic potential of genomic editing technologies. Targeted PCR amplification combined with Next Generation Sequencing (NGS) or enzymatic digestion, while broadly used in the genome editing field, has critical limitations for detecting and quantifying structural variants such as large deletions (greater than approximately 100 base pairs), inversions, and translocations. RESULTS: To overcome these limitations, we have developed a Uni-Directional Targeted Sequencing methodology, UDiTaS, that is quantitative, removes biases associated with variable-length PCR amplification, and can measure structural changes in addition to small insertion and deletion events (indels), all in a single reaction. We have applied UDiTaS to a variety of samples, including those treated with a clinically relevant pair of S. aureus Cas9 single guide RNAs (sgRNAs) targeting CEP290, and a pair of S. pyogenes Cas9 sgRNAs at T-cell relevant loci. In both cases, we have simultaneously measured small and large edits, including inversions and translocations, exemplifying UDiTaS as a valuable tool for the analysis of genome editing outcomes. CONCLUSIONS: UDiTaS is a robust and streamlined sequencing method useful for measuring small indels as well as structural rearrangements, like translocations, in a single reaction. UDiTaS is especially useful for pre-clinical and clinical application of gene editing to measure on- and off-target editing, large and small.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Rearranjo Gênico , Genoma Humano , Mutação INDEL , Osteossarcoma/diagnóstico , Antígenos de Neoplasias/genética , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/genética , Proteínas de Ciclo Celular , Células Cultivadas , Proteínas do Citoesqueleto , Genômica/métodos , Humanos , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Osteossarcoma/genética , Deleção de Sequência , Linfócitos T/metabolismo , Linfócitos T/patologia
17.
Nat Commun ; 8: 13905, 2017 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-28067217

RESUMO

The CRISPR-Cas9 system provides a versatile toolkit for genome engineering that can introduce various DNA lesions at specific genomic locations. However, a better understanding of the nature of these lesions and the repair pathways engaged is critical to realizing the full potential of this technology. Here we characterize the different lesions arising from each Cas9 variant and the resulting repair pathway engagement. We demonstrate that the presence and polarity of the overhang structure is a critical determinant of double-strand break repair pathway choice. Similarly, single nicks deriving from different Cas9 variants differentially activate repair: D10A but not N863A-induced nicks are repaired by homologous recombination. Finally, we demonstrate that homologous recombination is required for repairing lesions using double-stranded, but not single-stranded DNA as a template. This detailed characterization of repair pathway choice in response to CRISPR-Cas9 enables a more deterministic approach for designing research and therapeutic genome engineering strategies.


Assuntos
Proteína BRCA2/genética , Sistemas CRISPR-Cas , DNA/genética , Edição de Genes/métodos , Genoma Humano , Rad51 Recombinase/genética , Reparo de DNA por Recombinação , Proteína BRCA2/antagonistas & inibidores , Proteína BRCA2/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteína 9 Associada à CRISPR , Linhagem Celular Tumoral , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , DNA/metabolismo , Quebras de DNA de Cadeia Dupla , Endonucleases/genética , Endonucleases/metabolismo , Células HEK293 , Humanos , Células K562 , Osteoblastos/citologia , Osteoblastos/metabolismo , RNA Guia/genética , RNA Guia/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Rad51 Recombinase/antagonistas & inibidores , Rad51 Recombinase/metabolismo
18.
Environ Sci Pollut Res Int ; 23(13): 13413-23, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27026543

RESUMO

The effects of foliar application of proline (20 mM) on growth, physio-biochemical, and yield parameters were assessed in two Brassica juncea (L.) Czern & Coss cultivars, namely, Varuna and RH-30, at different levels (2.8, 4.2, or 5.6 dsm(-1)) of NaCl in soil. At 29 days after sowing (DAS), plants were sprayed with either 20 mM proline or water in the presence or absence of NaCl stress. The NaCl negatively affected parameters related to growth, photosynthesis, and yield in both varieties but more in RH-30 than in Varuna. Exogenous application of proline counteracted the effects of salt stress in Varuna only, by increasing the antioxidative capacity of the plants. Moreover, proline was not effective in alleviating the detrimental effects of higher salt concentrations on the studied parameters. Proline application to unstressed plants increased growth, photosynthesis, and yield parameters in both varieties; however, the effects were more prominent in Varuna than in RH-30.


Assuntos
Mostardeira/efeitos dos fármacos , Prolina/farmacologia , Substâncias Protetoras/farmacologia , Cloreto de Sódio/toxicidade , Poluentes do Solo/toxicidade , Mostardeira/crescimento & desenvolvimento , Mostardeira/metabolismo , Fotossíntese/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos
19.
J Anim Physiol Anim Nutr (Berl) ; 100(4): 649-56, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26847519

RESUMO

This study was conducted to replace soya bean meal with maggot meal at difference percentages. A total of 120 one-day-old broiler chicks were divided into four groups. Four diets were formulated with maggot meal to replace soya bean meal at the rate of 0%, 10%, 20% and 30% designated as A, B, C and D respectively. Feed and water were offered ad libitum during the study which lasted for 28 days. Feed intake decreased significantly in treated groups while body weight, Feed conversion ratio and dressing percentage increased significantly in group D. Apparent metabolizable energy increased significantly in the group fed 30% maggot meal; however, no significant difference was found in dry matter, crude protein, crude fibre, ether extract, ash and nitrogen free extract between the control and treated groups. The result of sensory evaluation revealed that tenderness and juiciness increased significantly in group C and B respectively. The colour and flavour were most accepted in group B and C. The results indicate that replacement of soya bean meal at the rate of 30% in broiler feed produced most favourable results.


Assuntos
Ração Animal/análise , Proteínas na Dieta/análise , Dípteros/química , Carne/análise , Soja/química , Fenômenos Fisiológicos da Nutrição Animal , Animais , Galinhas/fisiologia , Dieta/veterinária , Digestão , Metabolismo Energético , Larva/química
20.
J Infect Dev Ctries ; 10(1): 24-9, 2016 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-26829534

RESUMO

INTRODUCTION: Yellow fever (YF) is a vector-borne disease transmitted to humans by infected Aedes mosquitoes, while hepatitis E virus (HEV) is a waterborne disease that is transmitted through the fecal-oral route. Both diseases have very close clinical presentation, namely fever, jaundice, malaise, and dark urine; they differ in severity and outcome. METHODOLOGY: In this cross-sectional, laboratory-based study, an attempt was made to measure the correlation of concomitant YF and HEV infection in Darfur States during the previous YF outbreak in 2012. RESULTS: Results found concomitant outbreaks of YF and HEV at the same time with very weak statistical correlation between the two infections during the outbreak period, with Cramer's V correlation 0.05 and insignificant p value of 0.86. CONCLUSIONS: This correlation indicates that clinicians and care providers in tropical areas have to deal with clinical case definitions used for disease surveillance very carefully since prevalence of HEV infection is relatively common and this increases the possibility of misclassification and missing YF cases, particularly initial index cases, in a season or outbreak.


Assuntos
Surtos de Doenças , Hepatite E/epidemiologia , Febre Amarela/epidemiologia , Adolescente , Adulto , Idoso , Animais , Criança , Estudos Transversais , Feminino , Hepatite E/diagnóstico , Hepatite E/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Sudão/epidemiologia , Febre Amarela/diagnóstico , Febre Amarela/patologia , Adulto Jovem
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