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1.
Braz. j. biol ; 83: e246040, 2023. tab, graf
Artigo em Inglês | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1285610

RESUMO

Abstract Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by a congenitally reduced head circumference (-3 to -5 SD) and non-progressive intellectual disability. The objective of the study was to evaluate pathogenic mutations in the ASPM gene to understand etiology and molecular mechanism of primary microcephaly. Blood samples were collected from various families across different remote areas of Pakistan from February 2017 to May 2019 who were identified to be affected with primary microcephaly. DNA extraction was performed using the salting-out method; the quality and quantity of DNA were evaluated using spectrophotometry and 1% agarose gel electrophoresis, respectively in University of the Punjab. Mutation analysis was performed by whole exome sequencing from the Cologne Center for Genomics, University of Cologne. Sanger sequencing was done in University of the Punjab to confirm the pathogenic nature of mutation. A novel 4-bp deletion mutation c.3877_3880delGAGA was detected in exon 17 of the ASPM gene in two primary microcephaly affected families (A and B), which resulted in a frame shift mutation in the gene followed by truncated protein synthesis (p.Glu1293Lysfs*10), as well as the loss of the calmodulin-binding IQ domain and the Armadillo-like domain in the ASPM protein. Using the in-silico tools Mutation Taster, PROVEAN, and PolyPhen, the pathogenic effect of this novel mutation was tested; it was predicted to be "disease causing," with high pathogenicity scores. One previously reported mutation in exon 24 (c.9730C>T) of the ASPM gene resulting in protein truncation (p.Arg3244*) was also observed in family C. Mutations in the ASPM gene are the most common cause of MCPH in most cases. Therefore, enrolling additional affected families from remote areas of Pakistan would help in identifying or mapping novel mutations in the ASPM gene of primary microcephaly.


Resumo Microcefalia primária autossômica recessiva (MCPH) é um distúrbio do neurodesenvolvimento caracterizado por uma redução congênita do perímetro cefálico (-3 a -5 DP) e deficiência intelectual não progressiva. O objetivo do estudo foi avaliar mutações patogênicas no gene ASPM a fim de compreender a etiologia e o mecanismo molecular da microcefalia primária. Amostras de sangue foram coletadas de várias famílias em diferentes áreas remotas do Paquistão de fevereiro de 2017 a maio de 2019, que foram identificadas como afetadas com microcefalia primária. A extração do DNA foi realizada pelo método salting-out; a qualidade e a quantidade de DNA foram avaliadas por espectrofotometria e eletroforese em gel de agarose a 1%, respectivamente, na Universidade de Punjab. A análise de mutação foi realizada por sequenciamento completo do exoma do Cologne Center for Genomics, University of Cologne. O sequenciamento de Sanger foi feito na Universidade do Punjab para confirmar a natureza patogênica da mutação. Uma nova mutação de deleção de 4 bp c.3877_3880delGAGA foi detectada no exon 17 do gene ASPM em duas famílias afetadas por microcefalia primária (A e B), que resultou em uma mutação de frame shift no gene seguida por síntese de proteína truncada (pGlu1293Lysfs * 10), bem como a perda do domínio IQ de ligação à calmodulina e o domínio do tipo Armadillo na proteína ASPM. Usando as ferramentas in-silico Mutation Taster, PROVEAN e PolyPhen, o efeito patogênico dessa nova mutação foi testado; foi previsto ser "causador de doenças", com altos escores de patogenicidade. Uma mutação relatada anteriormente no exon 24 (c.9730C > T) do gene ASPM, resultando em truncamento de proteína (p.Arg3244 *) também foi observada na família C. Mutações no gene ASPM são a causa mais comum de MCPH na maioria dos casos . Portanto, a inscrição de famílias afetadas adicionais de áreas remotas do Paquistão ajudaria a identificar ou mapear novas mutações no gene ASPM da microcefalia primária.

2.
Braz J Biol ; 83: e246040, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34378666

RESUMO

Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by a congenitally reduced head circumference (-3 to -5 SD) and non-progressive intellectual disability. The objective of the study was to evaluate pathogenic mutations in the ASPM gene to understand etiology and molecular mechanism of primary microcephaly. Blood samples were collected from various families across different remote areas of Pakistan from February 2017 to May 2019 who were identified to be affected with primary microcephaly. DNA extraction was performed using the salting-out method; the quality and quantity of DNA were evaluated using spectrophotometry and 1% agarose gel electrophoresis, respectively in University of the Punjab. Mutation analysis was performed by whole exome sequencing from the Cologne Center for Genomics, University of Cologne. Sanger sequencing was done in University of the Punjab to confirm the pathogenic nature of mutation. A novel 4-bp deletion mutation c.3877_3880delGAGA was detected in exon 17 of the ASPM gene in two primary microcephaly affected families (A and B), which resulted in a frame shift mutation in the gene followed by truncated protein synthesis (p.Glu1293Lysfs*10), as well as the loss of the calmodulin-binding IQ domain and the Armadillo-like domain in the ASPM protein. Using the in-silico tools Mutation Taster, PROVEAN, and PolyPhen, the pathogenic effect of this novel mutation was tested; it was predicted to be "disease causing," with high pathogenicity scores. One previously reported mutation in exon 24 (c.9730C>T) of the ASPM gene resulting in protein truncation (p.Arg3244*) was also observed in family C. Mutations in the ASPM gene are the most common cause of MCPH in most cases. Therefore, enrolling additional affected families from remote areas of Pakistan would help in identifying or mapping novel mutations in the ASPM gene of primary microcephaly.


Assuntos
Microcefalia , Proteínas do Tecido Nervoso , Consanguinidade , Humanos , Microcefalia/genética , Mutação/genética , Proteínas do Tecido Nervoso/genética , Paquistão
3.
Int J Emerg Med ; 13(1): 5, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019485

RESUMO

BACKGROUND: Although the association of neutrophil to lymphocyte ratio (NLR) with mortality in trauma patients has recently been shown, there is a paucity of research on the association with other outcomes. Recent studies suggest that the NLR has a predictive value of mortality in trauma patients during various times of admission. This study aimed to determine the prognostic impact of NLR at the presentation in critically ill trauma patients. METHODS: A retrospective cohort study of adult trauma patients between July 2017 and November 2017 in Tishreen Hospital. All patients who had arrived at the emergency department with multi-trauma injury within the age category (14-80 years) were included in this analysis. The prophetical capability of NLR on mortality was assessed by the receiver operative characteristics (ROC) curve. To identify the impact of the NLR on survival, a separate log-rank test was used. Multivariable Cox proportional hazard modeling was used to identify independent predictors of mortality. RESULTS: Throughout the time of the study, 566 patients met the inclusion criteria. Of these, 98.8% were male, 75.8% sustained penetrating trauma, and median age [IQR25-IQR75] was 26 [23-32]. Ninety-seven patients (17.1%) had major trauma, with an Injury Severity Score (ISS) ≥ 15. Using the ROC curve analyses hospitalization day 1, optimal NLR cutoff values of 4.00 were calculated by maximizing the Youden index. Kaplan-Meier curves revealed an NLR greater than or equal to these cutoff values as a marker for increased in-hospital mortality (p = 0.020, log-rank test). The Cox regression model demonstrated significant collinearity among the predictive variables (all VIF results < 2). Only ISS > 15 has a significant statistical relation with elevated NLR on day 1 (p = 0.010). CONCLUSIONS: Elevated NLR on day 1 has high predictive power for overall survival during the first 30 days after trauma, but it was not independent of other factors.

5.
R. bras. Ci. avíc. ; 20(4): 789-796, Oct.-Dec. 2018. tab
Artigo em Inglês | VETINDEX | ID: vti-19744

RESUMO

This study was planned to evaluate subsequent effects of rearing under various lysine regimens on egg quality traits in Peshawari, Mushki, Mianwali and Lakha varieties of native Aseel. Ninety six pullets and 12 cockerels (24 and 3) from each variety were randomly chosen, placed in three-tiered cage units of equal space and standard conditions were followed for their maintenance. These birds were reared on three lysine regimens (L1, L2 and L3), wherein L1 containing 1.3% lysine was given in one phase from week 1-6 of age, L2 regimens entailing 1.4 and 1.2% lysine was smeared in two phases from week 1-3 and 4-6 of age, while in L3 regimen, lysine @ 1.5, 1.3 and 1.1% in diet was fed in three phases from week 1-2, 3-4 and 5-6 of age, respectively. Data were analyzed using two-way factorial ANOVA technique in SAS 9.1under randomized complete block design and significant means were compared through Duncans Multiple Range Test. Statistical analysis showed that weight of egg and shell, albumen weight, diameter and index, yolk weight and Haugh units (p≤0.05) improved significantly in L3 in Peshawari Aseel depicting the better egg quality traits. It was concluded that L3 regimen has positive impact on egg characteristics of Aseel chicken.(AU)


Assuntos
Animais , Ovos/análise , Lisina/administração & dosagem , Lisina/efeitos adversos , Proteínas do Ovo/análise , Galinhas , Ração Animal , Qualidade dos Alimentos
6.
J Dev Orig Health Dis ; 7(6): 665-671, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27453525

RESUMO

Prenatal and early-life environmental exposures play a key role in the development of atopy and allergic disease. The Family Atherosclerosis Monitoring In earLY life Study is a general, population-based Canadian birth cohort that prospectively evaluated prenatal and early-life traits and their association with atopy and/or allergic disease. The study population included 901 babies, 857 mothers and 530 fathers. Prenatal and postnatal risk factors were evaluated through questionnaires collected during the antenatal period and at 1 year. The end points of atopy and allergic diseases in infants were evaluated through questionnaires and skin prick testing. Key outcomes included atopy (24.5%), food allergy (17.5%), cow's milk allergy (4.8%), wheezing (18.6%) and eczema (16%). The association between infant antibiotic exposure [odds ratio (OR): 2.04, 95% confidence interval (CI): 1.45-2.88] and increased atopy was noted in the multivariate analysis, whereas prenatal maternal exposure to dogs (OR: 0.60, 95% CI: 0.42-0.84) and acetaminophen (OR: 0.68, 95% CI: 0.51-0.92) was associated with decreased atopy. This population-based birth cohort in Canada demonstrated high rates of atopy, food allergy, wheezing and eczema. Several previously reported and some novel prenatal and postnatal exposures were associated with atopy and allergic diseases at 1 year of age.


Assuntos
Aterosclerose/diagnóstico , Dermatite Atópica/diagnóstico , Hipersensibilidade/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Adulto , Animais , Criança , Cães , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Gravidez , Estudos Prospectivos
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