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1.
J Gene Med ; 26(7): e3714, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38949079

RESUMEN

Mouse models are used extensively to understand human pathobiology and mechanistic functions of disease-associated loci. However, in this review, we investigate the potential of using genetic mouse models to identify genetic markers that can disrupt hearing thresholds in mice and then target the hearing-enriched orthologues and loci in humans. Currently, little is known about the real prevalence of genes that cause hearing impairment (HI) in Africa. Pre-screening mouse cell lines to identify orthologues of interest has the potential to improve the genetic diagnosis for HI in Africa to a significant percentage, for example, 10-20%. Furthermore, the functionality of a candidate gene derived from mouse screening with heterogeneous genetic backgrounds and multi-omic approaches can shed light on the molecular, genetic heterogeneity and plausible mode of inheritance of a gene in hearing-impaired individuals especially in the absence of large families to investigate.


Asunto(s)
Modelos Animales de Enfermedad , Pérdida Auditiva , Animales , Humanos , Ratones , Pérdida Auditiva/genética , África/epidemiología , Predisposición Genética a la Enfermedad
2.
J Asthma ; 58(4): 488-496, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-31906746

RESUMEN

OBJECTIVE: The natural course of childhood asthma, after its onset, is characterized by periods of persistence, relapse and remission. To investigate personal and early life factors associated with new-onset asthma, persistence and remission among children. METHODS: The study was conducted in the province of Saskatchewan, Canada. Children in grades Kindergarten to Grade 8 (ages 5-14 years) participated in a cross-sectional study in 2013. In 2015, we approached those who gave consent in 2013 to be re-contacted, creating a prospective cohort. Data were collected using questionnaires in both years. Participants in 2013 who also had data in 2015 (25%: n = 324/1,348) had their asthma status reclassified and longitudinal descriptors were applied: "no asthma", "new-onset asthma", "persistent" or "remission". Personal and early life factors associations with asthma outcomes in 2015 were evaluated. RESULTS: Among those without asthma in 2013 (n = 245), the incidence of new-onset asthma in 2015 was 7.2%. Among those with asthma in 2013 (n = 79), 47.1% had remission and 52.9% had persistent asthma in 2015. Parental history of asthma (adjusted odds ratio (aOR): 4.99; 95% confidence interval (CI): 1.88-28.27), early life respiratory infection (aOR: 1.92; 95%CI: 1.47-7.88), early life allergy [aOR: 6.39; 95%CI: 1.34-30.58) and early life infection (aOR: 4.99; 95%CI: 1.19-20.93) were associated with new onset asthma. Similarly, while parental history of asthma (aOR: 1.13; 95%CI: 0.29-4.34), early life respiratory infection (aOR: 2.71; 95%CI: 0.70-10.45), and early life ear infection (aOR: 1.34; 95%CI: 0.36-5.05) were also positively association with persistent asthma, the associations were not statistically significant. CONCLUSION: Parental history of asthma, early life respiratory infection and allergy might not only influence the onset of childhood asthma but also be associated with asthma persistence.


Asunto(s)
Asma/epidemiología , Asma/fisiopatología , Adolescente , Factores de Edad , Animales , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Hipersensibilidad/epidemiología , Masculino , Anamnesis , Otitis/epidemiología , Mascotas , Estudios Prospectivos , Remisión Espontánea , Características de la Residencia , Pruebas de Función Respiratoria , Infecciones del Sistema Respiratorio/epidemiología , Factores de Riesgo , Saskatchewan/epidemiología
3.
BMC Med Genet ; 21(1): 23, 2020 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-32019516

RESUMEN

BACKGROUND: The prevalence of Parkinson's disease (PD) is increasing in sub-Saharan Africa, but little is known about the genetics of PD in these populations. Due to their unique ancestry and diversity, sub-Saharan African populations have the potential to reveal novel insights into the pathobiology of PD. In this study, we aimed to characterise the genetic variation in known and novel PD genes in a group of Black South African and Nigerian patients. METHODS: We recruited 33 Black South African and 14 Nigerian PD patients, and screened them for sequence variants in 751 genes using an Ion AmpliSeq™ Neurological Research panel. We used bcftools to filter variants and annovar software for the annotation. Rare variants were prioritised using MetaLR and MetaSVM prediction scores. The effect of a variant on ATP13A2's protein structure was investigated by molecular modelling. RESULTS: We identified 14,655 rare variants with a minor allele frequency ≤ 0.01, which included 2448 missense variants. Notably, no common pathogenic mutations were identified in these patients. Also, none of the known PD-associated mutations were found highlighting the need for more studies in African populations. Altogether, 54 rare variants in 42 genes were considered deleterious and were prioritized, based on MetaLR and MetaSVM scores, for follow-up studies. Protein modelling showed that the S1004R variant in ATP13A2 possibly alters the conformation of the protein. CONCLUSIONS: We identified several rare variants predicted to be deleterious in sub-Saharan Africa PD patients; however, further studies are required to determine the biological effects of these variants and their possible role in PD. Studies such as these are important to elucidate the genetic aetiology of this disorder in patients of African ancestry.


Asunto(s)
Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Enfermedad de Parkinson/genética , ATPasas de Translocación de Protón/genética , Adulto , Anciano , Anciano de 80 o más Años , Población Negra/genética , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Anotación de Secuencia Molecular , Mutación Missense , Nigeria/epidemiología , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/patología , Mutación Puntual , Sudáfrica/epidemiología
4.
J Asthma ; 55(11): 1242-1252, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29420108

RESUMEN

OBJECTIVE: Studies have reported lower asthma prevalence in rural compared to urban areas. While environmental factors have mostly been implicated for these differences, the lower asthma prevalence could also be linked to asthma under-diagnosis in rural children. We investigate if rural children experience under-diagnosis of asthma more compared to urban children. METHODS: In 2013, we conducted a cross-sectional survey of schoolchildren across an urban-rural gradient in Saskatchewan, Canada. The participants formed sampling frame for future studies. In 2015, we approached those who gave consent in 2013 for further testing, repeated the survey, and conducted clinical testing. Based on survey responses, children were classified into "no asthma," "at-risk-for-asthma," and "diagnosed asthma." We then classified asthma status as either "no asthma" or "probable asthma" based on a validated asthma algorithm. RESULTS: The study population of 335 schoolchildren (aged 7-17 years) comprised of 73.4% from large urban, 13.7% from small urban, and 12.8% from rural areas. Proportion with report of physician-diagnosed asthma was 28.5% (Large urban), 34.8% (Small urban), and 20.9% (Rural). Mean percent predicted FEV1 and FEF25%-75% were lower in rural compared to small urban and large urban children (p < 0.05). Among those not classified as with "diagnosed asthma" by the survey, the algorithm further identified presence of asthma in 5.5% large urban, 8.1% small urban, and 18.8% rural children (p = 0.03). CONCLUSION: The study revealed evidence of asthma underdiagnosis in rural areas and further supports the use of objective measures in addition to symptoms history when investigating asthma across urban-rural gradients.


Asunto(s)
Asma/diagnóstico , Asma/epidemiología , Población Rural/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Algoritmos , Asma Inducida por Ejercicio/diagnóstico , Asma Inducida por Ejercicio/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Prevalencia , Pruebas de Función Respiratoria , Factores de Riesgo , Saskatchewan/epidemiología , Factores Socioeconómicos
5.
Environ Res ; 164: 302-309, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29554621

RESUMEN

BACKGROUND: Studies have reported protective and adverse associations between microbial exposure and childhood asthma. However, among children with asthma the relationships between endotoxin and exercise-induced bronchospasm (EIB) is less clear. OBJECTIVE: We investigated the association between exposure to endotoxin in house dust with atopy and EIB in children with asthma. METHODS: A cross-sectional survey was conducted among schoolchildren (aged 7-17 years) in the province of Saskatchewan, Canada. A subpopulation with asthma (n = 116) were identified from 335 participants using a validated asthma algorithm. We determined atopy among the asthma subpopulation by skin prick testing (SPT) while EIB was evaluated using exercise challenge testing (ECT). Dust samples were collected from mattress and play area floors, and endotoxin was measured in dust extracts. Logistic regression analyses were used to explore associations between endotoxin with atopy and EIB. RESULTS: Among the 116 children with asthma, 99 completed SPT and all had completed ECT. Of these, 71/99 (71.7%) were atopic and 26/116 (22.4%) had EIB. Exposure to high play area endotoxin concentration [adjusted odds ratio (aOR) = 0.15, 95% CI: 0.03-0.85] and load (aOR = 0.11, 95% CI: 0.02-0.73) were negatively associated with atopy. In contrast, EIB was positively associated with high mattress endotoxin concentration (aOR = 6.01, 95% CI: 1.20-30.13). CONCLUSION: Indoor microbial endotoxin exposure has varied associations with atopy and exercise-induced bronchospasm among children with asthma.


Asunto(s)
Asma Inducida por Ejercicio , Asma , Polvo , Adolescente , Alérgenos , Asma/epidemiología , Asma Inducida por Ejercicio/epidemiología , Canadá , Niño , Estudios Transversales , Endotoxinas , Exposición a Riesgos Ambientales , Femenino , Humanos , Masculino
6.
J Asthma ; 54(4): 347-356, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27589676

RESUMEN

BACKGROUND: Approximately 70% of rural Nigerian households rely on biomass fuels for cooking. The International Study of Asthma and Allergies in Childhood (ISAAC) estimates the prevalence of current wheeze among children in Nigeria to have risen from 10.7% in 1999 to approximately 20% in 2014. OBJECTIVE: To examine the effects of biomass smoke exposure on asthma symptom prevalence in rural children in Nigeria. METHODS: We conducted a cross-sectional survey in rural communities in Nigeria. Asthma symptoms were defined according to ISAAC definitions. Biomass smoke exposure was determined by the types of fuel used for cooking. Logistic regression was used to explore associations between biomass smoke and asthma symptoms. RESULTS: The study population comprised 1,690 school children, of which 865 lived in households cooking with biomass and 825 lived in households not using biomass. Asthma symptoms were reported in 481 (28.5%) children. Biomass fuel was associated with increased odds of asthma symptoms. Adjusted odds ratios (aORs) were 1.38 (95% CI: 1.05-1.80) for nocturnal cough, 1.26 (95% CI: 1.00-1.61) for current wheeze, and 1.33 (95% CI: 1.05-1.69) for report of any asthma-related symptoms. Sex modified the associations between asthma symptoms with biomass fuel: aORs were stronger and significant for males (nocturnal cough = 1.85, 95% CI: 1.24-2.76; current wheeze = 1.48, 95% CI: 1.03-2.13; report of any asthma-related symptoms = 1.60, 95% CI: 1.12-2.28), but weaker and non-significant for females. CONCLUSION: The risk of asthma symptoms related to biomass smoke exposure appears to differ by sex.


Asunto(s)
Contaminación del Aire Interior/efectos adversos , Asma/epidemiología , Culinaria/métodos , Población Rural/estadística & datos numéricos , Humo/efectos adversos , Adolescente , Niño , Tos , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Masculino , Nigeria/epidemiología , Prevalencia , Ruidos Respiratorios , Factores Sexuales , Factores Socioeconómicos , Adulto Joven
7.
BMC Pulm Med ; 17(1): 3, 2017 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-28056916

RESUMEN

BACKGROUND: In 2014, the International Study of Asthma and Allergies in Childhood (ISAAC) reported that the highest prevalence of symptoms of severe asthma was found in the low- and middle-income countries (LMICs), including Nigeria. While exposure to biomass fuel use may be an important risk factor in the development of asthma, its association with asthma symptoms severity has not been well-established. The aim of this study is to extend the spectrum of environmental risk factors that may be contributing towards increasing asthma morbidity, especially asthma symptoms severity in rural schoolchildren in Nigeria and to examine possible asthma underdiagnosis among this population. METHODS: Authors conducted a cross-sectional survey in three rural communities in Nigeria. Asthma symptoms were defined according to the ISAAC criteria. Information on the types of household fuel used for cooking was used to determine household cooking fuel status. Asthma symptoms severity was defined based on frequencies of wheeze, day- and night-time symptoms, and speech limitations. Logistic regression analyses were used to explore associations. RESULTS: A total of 1,690 Nigerian schoolchildren participated in the study. Overall, 37 (2.2%) had diagnosed asthma and 413 (24.4%) had possible asthma (asthma-related symptoms but not diagnosed asthma). Children from biomass fuel households had higher proportion of possible asthma (27.7 vs. 22.2%; p < 0.05) and symptoms of severe asthma (18.2 vs. 7.6%; p = 0.048). In adjusted analyses, biomass fuel use was associated with increased odds of severe symptoms of asthma [odds ratios (OR) = 2.37; 95% CI: 1.16-4.84], but not with possible asthma (OR = 1.22; 95% CI: 0.95-1.56). CONCLUSION: In rural Nigerian children with asthma symptoms, the use of biomass fuel for cooking is associated with an increased risk of severe asthma symptoms. There is additional evidence that rural children might be underdiagnosed for asthma.


Asunto(s)
Contaminación del Aire Interior/efectos adversos , Asma/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Adolescente , Biomasa , Niño , Culinaria , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Masculino , Morbilidad , Análisis Multivariante , Nigeria/epidemiología , Ruidos Respiratorios/etiología , Factores de Riesgo , Población Rural
8.
BMC Pulm Med ; 17(1): 4, 2017 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-28056923

RESUMEN

BACKGROUND: Asthma prevalence is generally lower in rural locations with some indication of an urban-rural gradient. However, among children with asthma, certain rural exposures thought to protect against the development of asthma could aggravate the condition. We examined childhood asthma prevalence and related conditions along an urban-rural gradient and also examined the characteristics of those with asthma along the urban-rural gradient. METHODS: In 2013 we completed a cross-sectional survey of 3509 children aged 5-14 years living in various population densities of Saskatchewan, Canada. Location of dwelling was identified as belonging to one of the following population densities: large urban region (approximately 200,000), small urban (approximately 35,000), or rural (small town of <1,500 or farm dweller). Physician-diagnosed asthma and asthma-related symptoms were ascertained from responses in the parental-completed questionnaires. RESULTS: Of the study population, 69% lived in a large urban region, 11% lived in a small urban centre and 20% were rural dwellers. Overall, asthma prevalence was 19.6% with differences in asthma prevalence with differences between locations (large urban = 20.7%; small urban = 21.5%; rural = 15.1%; p = 0.003). After adjustment for potential confounders, the association between location of dwelling and asthma remained significant. Despite a lower prevalence of asthma in the rural area, the prevalence and risk of ever wheeze and having more than 3 wheezing episodes in the past 12 months among those who reported asthma, was higher in rural locations after adjustment for potential confounders. CONCLUSIONS: The results of this study support the evidence of a difference in childhood asthma prevalence between urban and rural locations and that once a child has asthma, certain rural exposures may aggravate the disease.


Asunto(s)
Asma/epidemiología , Disparidades en el Estado de Salud , Hipersensibilidad/epidemiología , Población Rural/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Niño , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Masculino , Morbilidad , Prevalencia , Ruidos Respiratorios/etiología , Factores de Riesgo , Saskatchewan/epidemiología , Encuestas y Cuestionarios
11.
Open Med (Wars) ; 19(1): 20240917, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38463519

RESUMEN

Causal mutations in the MCPH1 gene have been associated with disorders like microcephaly, and recently congenital hearing impairment. This study examined the MCPH1 DNA repair machinery and identified genetic variations of interest in gnomAD database to discuss the biological roles and effects of rare variants in MCPH1-related diseases. Notably, MCPH1 coordinates two of the seven known mechanisms of DNA repair which confirmed its roles in neurogenesis and chromatin condensation. A pathogenic missense variant in MCPH1 p.Gly753Arg, and two pathogenic frameshifts MCPH1 p.Asn189LysfsTer15 and p.Cys624Ter identified in this study, already had entries in ClinVar and were associated with microcephaly. A pathogenic frameshift in MCPH1 p.Val10SerfsTer5 with a loss-of-function flag and a pathogenic stop gained p.Ser571Ter variants with ultra-rare allele frequency (MAF ≤ 0.001) were identified but have not been linked to any phenotype. The predicted pathogenic ultra-rare variants identified in this study, warranty phenotypic discovery, and also positioned these variants or nearby deleterious variants candidate for screening in MCPH1-associated rare diseases.

12.
Can J Diabetes ; 48(2): 74-81, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37839678

RESUMEN

BACKGROUND: The dried blood spot (DBS) card is a novel collection method for measuring glycated hemoglobin (A1C) in individuals with diabetes mellitus. The potential benefits of DBS specimens compared with traditional phlebotomy include a reduction in required total blood volume, reduced procedural pain, and an ability for self-initiated collection. DBS cards for A1C measurement have been validated in the adult population, but there is a paucity of pediatric data. METHODS: The aim of this study was to validate the use of A1C measurement by DBS cards in comparison to venous A1C and to identify potential barriers to implementing this novel approach. Venous and DBS card A1C samples were collected simultaneously from 62 patients at their local laboratory and transported to the central provincial lab for analysis. Correlation analyses compared venous and DBS A1C with data rescaling performed to account for the DBS-venous interassay difference. RESULTS: Mean venous A1C was 7.49% and DBS A1C was 7.26%, with an interassay difference of 0.23%. Data showed a strong, positive correlation between A1C collection methods (r=0.86, p<0.001); this was further strengthened at lower A1C values (A1C <7.5%, r=0.87, p<0.0001). A stronger relationship emerged when the data were rescaled to account for the DBS-venous interassay difference (r=0.8935, p<0.0001). CONCLUSIONS: Given the potential feasibility, practicality, accessibility, cost-effectiveness, and performance characteristics of the DBS A1C, especially at lower A1C values hovering around the diagnostic threshold for diabetes, this study provides supporting evidence for consideration of the use of DBS A1C testing in pediatric diabetes care.


Asunto(s)
Diabetes Mellitus , Adulto , Humanos , Niño , Hemoglobina Glucada , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/terapia , Flebotomía , Pruebas con Sangre Seca
13.
Curr Med Res Opin ; 39(1): 141-147, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36094413

RESUMEN

The large-scale implementation of genomic medicine in Africa has not been actualized. This overview describes how routine molecular genetics and advanced protein engineering/structural biotechnology could accelerate the implementation of genomic medicine. By using data-mining and analysis approaches, we analyzed relevant information obtained from public genomic databases on pharmacogenomics biomarkers and reviewed published studies to discuss the ideas. The results showed that only 68 very important pharmacogenes currently exist, while 867 drug label annotations, 201 curated functional pathways, and 746 annotated drugs have been catalogued on the largest pharmacogenomics database (PharmGKB). Only about 5009 variants of the reported ∼25,000 have been clinically annotated. Predominantly, the genetic variants were derived from 43 genes that contribute to 2318 clinically relevant variations in 57 diseases. Majority (∼60%) of the clinically relevant genetic variations in the pharmacogenes are missense variants (1390). The enrichment analysis showed that 15 pharmacogenes are connected biologically and are involved in the metabolism of cardiovascular and cancer drugs. The review of studies showed that cardiovascular diseases are the most frequent non-communicable diseases responsible for approximately 13% of all deaths in Africa. Also, warfarin pharmacogenomics is the most studied drug on the continent, while CYP2D6, CYP2C9, DPD, and TPMT are the most investigated pharmacogenes with allele activities indicated in African and considered to be intermediate metaboliser for DPD and TPMT (8.4% and 11%). In summary, we highlighted a framework for implementing genomic medicine starting from the available resources on ground.


Asunto(s)
Medicina Genómica , Farmacogenética , Humanos , Farmacogenética/métodos , Warfarina/uso terapéutico , África , Biología Molecular
14.
Open Med (Wars) ; 17(1): 61-69, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34993346

RESUMEN

Several causative factors are associated with hearing loss (HL) and brain disorders. However, there are many unidentified disease modifiers in these conditions. Our study summarised the most common brain disorders associated with HL and highlighted mechanisms of pathologies. We searched the literature for published articles on HL and brain disorders. Alzheimer's disease/dementia, Parkinson's disease, cognitive impairment, autism spectrum disorder, ataxia, epilepsy, stroke, and hypoxic-ischaemic encephalopathy majorly co-interact with HL. The estimated incidence rate was 113 per 10,000 person-years. Genetic, epigenetic, early life/neonatal stress, hypoxia, inflammation, nitric oxide infiltration, endoplasmic reticulum stress, and excess glutamate were the distinguished modifiers identified. Various mechanisms like adhesion molecules, transport proteins, hair cell apoptosis, and neurodegeneration have been implicated in these conditions and are serving as potential targets for therapies. To improve the quality of life of patients, these understandings will improve clinical diagnoses and management of HL and brain disorders.

15.
Saudi J Anaesth ; 15(2): 101-108, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34188625

RESUMEN

BACKGROUND: Obstructive sleep apnea (OSA) is prevalent in the surgical patient population and is associated with high risk of perioperative complications. There are limited guidelines and wide practice variations regarding the perioperative care of obese and OSA patients. This is a study of European anesthesiologists' clinical practice of perioperative care of OSA patients. METHODS: This survey evaluated United Kingdom anesthesiologists' clinical practice of the perioperative care of OSA patients. Outcomes and variables were compared between 4100 anesthesiologists of different clinical experience and hospital settings. RESULTS: Approximately 45% of respondents manage OSA patients rarely, 42% occasionally, and 13% regularly. Most respondents order OSA screening tests if patients have tonsillar hypertrophy, head/neck tumor, BMI >35, increased neck circumference, craniofacial anomaly, and right-sided electrocardiography (ECG) anomaly. Majority request preoperative polysomnography, ECG, overnight pulse oximetry, and arterial blood gas analysis. Majority recommend preoperative weight loss, optimisation, smoking cessation, reduction of substance use, and regular mask-CPAP use. Majority consider endoscopy, and ophthalmology as appropriate day case procedures, but not laparoscopy. Majority postpone elective airway, laparoscopic, laparotomy, and head/neck surgery; if patients are not optimized preoperatively. For major surgery, combined general + neuraxial anesthesia was ranked as 3rd option. For major limb surgery, neuraxial anesthesia without sedation was ranked as 1st option, nerve block without sedation was ranked 2nd, and general anesthesia + nerve block was ranked 3rd or 4th. At anesthesia emergence, majority ensure that patients have normal consciousness, respiration and neuromuscular function. Majority ensure postoperative oximetry, telemetry, and oxygen supplementation. CONCLUSION: This study highlights variations in anesthesiologists' perioperative care of OSA patients; even in developed countries with advanced medical training and standards. The study outcomes will improve perioperative care of OSA patients.

16.
Exp Biol Med (Maywood) ; 246(2): 197-206, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32996353

RESUMEN

Physiologically, the human and murine hearing systems are very similar, justifying the extensive use of mice in experimental models for hearing impairment (HI). About 340 murine HI genes have been reported; however, whether variants in all human-mouse ortholog genes contribute to HI has been rarely investigated. In humans, nearly 120 HI genes have been identified to date, with GJB2 and GJB6 variants accounting for half of congenital HI cases, of genetic origin, in populations of European and Asian ancestries, but not in most African populations. The contribution of variants in other known genes of HI among the populations of African ancestry is poorly studied and displays the lowest pick-up rate. We used whole exome sequencing (WES) to investigate pathogenic and likely pathogenic (PLP) variants in 34 novel human-mouse orthologs HI genes, in 40 individuals from Cameroon and South Africa diagnosed with non-syndromic hearing impairment (NSHI), and compared the data to WES data of 129 ethnically matched controls. In addition, protein modeling for selected PLP gene variants, gene enrichment, and network analyses were performed. A total of 4/38 murine genes, d6wsu163e, zfp719, grp152 and minar2, had no human orthologs. WES identified three rare PLP variants in 3/34 human-mouse orthologs genes in three unrelated Cameroonian patients, namely: OCM2, c.227G>C p.(Arg76Thr) and LRGI1, c.1657G>A p.(Gly533Arg) in a heterozygous state, and a PLP variant MCPH1, c.2311C>G p.(Pro771Ala) in a homozygous state. In silico functional analyses suggest that these human-mouse ortholog genes functionally co-expressed interactions with well-established HI genes: GJB2 and GJB6. The study found one homozygous variant in MCPH1, likely to explain HI in one patient, and suggests that human-mouse ortholog variants could contribute to the understanding of the physiology of hearing in humans.


Asunto(s)
Población Negra/genética , Secuenciación del Exoma , Pérdida Auditiva/genética , Adolescente , Adulto , Animales , Proteínas de Transporte de Anión/genética , Proteínas de Ciclo Celular/química , Niño , Preescolar , Proteínas del Citoesqueleto/química , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Variación Genética , Genética de Población , Humanos , Lactante , Recién Nacido , Ratones , Análisis de Componente Principal , ARN/genética , Termodinámica
17.
Front Pediatr ; 9: 726776, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34912757

RESUMEN

Objectives: To identify the etiologies of hearing impairment (HI) in schools for students who are deaf and to use a systematic review to summarize reports on the etiologies and clinical and genetic features of HI in Mali. Methods: We included individuals with HI that started before the age of 15 years old. Patients were carefully evaluated under standard practices, and pure-tone audiometry was performed where possible. We then searched for articles published on HI in the Malian population from the databases' inception to March 30, 2020. Results: A total of 117 individuals from two schools for the deaf were included, and a male predominance (sex ratio 1.3; 65/52) was noted. HI was pre-lingual in 82.2% (n = 117), and the median age at diagnosis was 12 years old. The etiologies were environmental in 59.4% (70/117), with meningitis being the leading cause (40%, 20/70), followed by cases with genetic suspicion (29.3%, 21/117). In 11.3% (8/117) of patients, no etiology was identified. Among cases with genetic suspicion, three were syndromic, including two cases of Waardenburg syndrome, while 15 individuals had non-syndromic HI. An autosomal recessive inheritance pattern was observed in 83.3% of families (15/18), and consanguinity was reported in 55.5% (10/18) of putative genetic cases. Conclusion: This study concludes that environmental factors are the leading causes of HI in Mali. However, genetic causes should be investigated, particularly in the context of a population with a high consanguinity rate.

18.
Drug Metab Pers Ther ; 35(4)2020 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-32887181

RESUMEN

OBJECTIVES: Repeated exposure to anoxic stress damages the brain through cortisol-mediated increases in oxidative stress and cellular-antioxidants depletion. Thus, compounds with antioxidant property might confer protection against anoxic stress-induced brain injuries. In this study, we further examined the protective effect of methyl jasmonate (MJ), a potent anti-stress agent against anoxic stress-induced convulsions in mice. METHODS: Thirty-six male Swiss mice randomized into six groups (n=6) were given MJ (25, 50 and 100 mg/kg, i.p.) or vehicle (10 mL/kg, i.p.) 30 min before 15 min daily exposure to anoxic stress for 7 days. The latency(s) to anoxic convulsion was recorded on day 7. The blood glucose and serum corticosterone levels were measured afterwards. The brains were also processed for the determination of malondialdehyde, nitrite, and glutathione levels. RESULTS: Methyl jasmonate (MJ) delayed the latency to anoxic convulsion and reduced the blood glucose and serum corticosterone levels. The increased malondialdehyde and nitrite contents accompanied by decreased glutathione concentrations in mice with anoxic stress were significantly attenuated by MJ. CONCLUSIONS: These findings further showed that MJ possesses anti-stress property via mechanisms relating to the reduction of serum contents of corticosterone and normalization of brain biomarker levels of oxidative stress in mice with anoxic stress.


Asunto(s)
Corticosterona , Estrés Oxidativo , Acetatos , Animales , Antioxidantes/farmacología , Biomarcadores/metabolismo , Encéfalo , Corticosterona/farmacología , Ciclopentanos , Humanos , Masculino , Ratones , Oxilipinas , Convulsiones
19.
Pediatr Pulmonol ; 55(8): 1924-1935, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32478962

RESUMEN

BACKGROUND: The natural course of asthma may differ depending on the age of onset. OBJECTIVE: To investigate predictors of asthma remission with a focus on the age of asthma onset. METHODS: The study was a retrospective birth cohort of children with asthma in Saskatchewan, Canada. Using the Saskatchewan Ministry of Health databases, we identified children with a diagnosis of asthma in the first 6 years of life and who had at least 10 years of follow-up after diagnosis (n = 22 563). Of these, we included 6393 children either with persistent asthma (≥1 physician visit or hospitalization for asthma [PVHA] during each year of follow-up) and those who had remission (had PVHA in the first year after diagnosis but at some point during the follow-up no longer received PVHA until end of the study). We used survival analysis to examine associations between remission and age of asthma onset. RESULTS: Of the study participants, 87.2% had early-onset (≤3 years) and 12.8% had late-onset (4-6 years) asthma. Over the 10-years of follow-up, the rate of asthma remission was 37 per 100 person-years. Early-onset asthma (hazard ratio [HR] = 1.10; 95%confidence interval [CI]: 1.01-1.20), being female (HR = 1.12; 95%CI: 1.07-1.18), living in a rural (HR = 1.20; 95%CI: 1.14-1.27) and medium urban (HR = 1.16; 95%CI: 1.08-1.26) location were positively associated with remission while history of atopy decreased likelihood of remission (HR = 0.73; 95%CI: 0.54-0.97). CONCLUSION: Most children with asthma experienced remission, especially those with the onset of symptoms within the first 3 years of life.


Asunto(s)
Asma/diagnóstico , Adolescente , Edad de Inicio , Asma/epidemiología , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Modelos de Riesgos Proporcionales , Remisión Espontánea , Estudios Retrospectivos , Factores de Riesgo , Población Rural , Saskatchewan/epidemiología
20.
Genes (Basel) ; 11(2)2020 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-32098311

RESUMEN

The incidence of hearing impairment (HI) is higher in low- and middle-income countries when compared to high-income countries. There is therefore a necessity to estimate the burden of this condition in developing world. The aim of our study was to use a systematic approach to provide summarized data on the prevalence, etiologies, clinical patterns and genetics of HI in Cameroon. We searched PubMed, Scopus, African Journals Online, AFROLIB and African Index Medicus to identify relevant studies on HI in Cameroon, published from inception to 31 October, 2019, with no language restrictions. Reference lists of included studies were also scrutinized, and data were summarized narratively. This study is registered with PROSPERO, number CRD42019142788. We screened 333 records, of which 17 studies were finally included in the review. The prevalence of HI in Cameroon ranges from 0.9% to 3.6% in population-based studies and increases with age. Environmental factors contribute to 52.6% to 62.2% of HI cases, with meningitis, impacted wax and age-related disorder being the most common ones. Hereditary HI comprises 0.8% to 14.8% of all cases. In 32.6% to 37% of HI cases, the origin remains unknown. Non-syndromic hearing impairment (NSHI) is the most frequent clinical entity and accounts for 86.1% to 92.5% of cases of HI of genetic origin. Waardenburg and Usher syndromes account for 50% to 57.14% and 8.9% to 42.9% of genetic syndromic cases, respectively. No pathogenic mutation was described in GJB6 gene, and the prevalence of pathogenic mutations in GJB2 gene ranged from 0% to 0.5%. The prevalence of pathogenic mutations in other known NSHI genes was <10% in Cameroonian probands. Environmental factors are the leading etiology of HI in Cameroon, and mutations in most important HI genes are infrequent in Cameroon. Whole genome sequencing therefore appears as the most effective way to identify variants associated with HI in Cameroon and sub-Saharan Africa in general.


Asunto(s)
Pérdida Auditiva/epidemiología , Pérdida Auditiva/genética , Pérdida Auditiva/fisiopatología , África/epidemiología , Camerún/epidemiología , Conexinas/genética , Sordera/epidemiología , Sordera/genética , Genotipo , Pérdida Auditiva Sensorineural/epidemiología , Humanos , Incidencia , Mutación/genética , Prevalencia
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