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1.
PLoS One ; 14(8): e0221672, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31437235

RESUMEN

[This corrects the article DOI: 10.1371/journal.pone.0218443.].

2.
PLoS One ; 14(6): e0218443, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31211820

RESUMEN

Low serum levels of high-density lipoprotein cholesterol (HDL-C) have been shown to be a risk factor for coronary artery disease independent of low-density lipoprotein cholesterol (LDL-C) in different populations. In this study, we investigated genetic variants through genome-wide association studies to determine their association with HDL-C levels in a sample of 2,700 patients. We identified several SNPs associated with HDL-C levels in the Lebanese population using unadjusted and adjusted by biological factors models. We replicated the association of rs3764261 within CETP with HDL-C levels in the study population, and found other previously unidentified SNPs to be significant at the suggestive level, in both previously identified and unidentified genes. This paper reports the first genome-wide analysis of HDL-C in the Lebanese, Middle Eastern, population and supports the importance of genome-wide association studies across different and minor ethnicities to understand better the etiology of complex human diseases.

3.
BMC Infect Dis ; 18(1): 710, 2018 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-30594126

RESUMEN

BACKGROUND: Lebanon hosts a heterogeneous population coming from underdeveloped and developing countries, resulting in increasing incidences of tuberculosis over the past years. The genetic heterogeneity and lineages associated with tuberculosis, along with their resistance determinants have not been studied at the genomic level previously in the region. METHODS: Isolates were recovered from the American University of Beirut Medical Center (AUBMC). Antimicrobial susceptibility profiles were determined using the MGIT automated system for the first-line drugs at AUBMC, while second-line drug susceptibility was tested at Mayo Clinic Laboratories. Whole Genome Sequencing (WGS) was performed to classify mycobacterial lineages and highlight single nucleotide mutations causing resistance to both 1st line and 2nd line antimicrobials. wgSNP analysis provided insights on the phylogeny of the isolates along with spoligotyping and core genomic SNVs, IS6110 insertion sites, and variable number tandem repeats (VNTR). RESULTS: The analyzed isolates carry distinct resistance determinants to isoniazid, rifampicin, ethambutol, quinolones, and streptomycin. The isolates belonged to different lineages including the Euro/American lineage (Lineage 4) (53.8%), M. bovis (15.4%) and Delhi/Central Asia (Lineage 1) (15.4%), Beijing/East Asia (Lineage 2) (7.7%), and East Africa/Indian Ocean lineage (Lineage 3) (7.7%) showing great phylogenetic differences at the genomic level. CONCLUSIONS: The population diversity in Lebanon holds an equally diverse and uncharacterized population of drug resistant mycobacteria. To achieve the WHO "END-TB" milestones of 2025 and 2035, Lebanon must decrease TB incidences by 95% in the next decade. This can only be done through WGS-based patient centered diagnosis with higher throughput and genomic resolution to improve treatment outcomes and to monitor transmission patterns.


Asunto(s)
Variación Genética , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Adulto , Técnicas de Tipificación Bacteriana , Femenino , Genotipo , Humanos , Isoniazida/uso terapéutico , Líbano/epidemiología , Masculino , Persona de Mediana Edad , Repeticiones de Minisatélite , Mutación , Mycobacterium tuberculosis/clasificación , Filogenia , Polimorfismo de Nucleótido Simple , Rifampin/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología
4.
Obes Surg ; 28(2): 396-404, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28776151

RESUMEN

PURPOSE: Long-term studies on the outcomes of bariatric surgery are still limited in the Middle East. The aim of this study is to compare the outcomes of laparoscopic Roux-en-Y gastric bypass (LRYGB) and sleeve gastrectomy (LSG) up to 5 years of follow-up. MATERIALS AND METHODS: A retrospective analysis of patients who underwent LRYGB and LSG was performed. The primary outcome was weight loss. Postoperative complications, operative time, and hospital length of stay were secondary outcomes. RESULTS: Four hundred patients underwent primary LSG and 175 patients underwent LRYGB between 2008 and 2013. Follow-up rates at 5 years were around 60%. Percent total weight loss was similar after 3, 4, and 5 years in both groups, averaging around 28%. Mean percentage of excess weight loss (%EWL) at 5 years was 72.0 ± 31.0% in the LSG group vs. 63.0 ± 21.0% in the LRYGB group (p = 0.03). Patients undergoing LRYGB had a significantly longer operative time as well as a longer hospital stay. No significant difference was found in the rates of short- and long-term complications between the two groups. However, patients undergoing LRYGB were more likely to develop small intestinal obstruction and iron-deficiency anemia. CONCLUSIONS: Both LSG and LRYGB result in satisfactory weight loss within 5 years. Patients' comorbidities and potential risks must be included in the choice of the appropriate bariatric procedure. LSG appears to give durable weight loss with less risk of major long-term complications.


Asunto(s)
Gastrectomía , Derivación Gástrica , Obesidad Mórbida/cirugía , Adolescente , Adulto , Comorbilidad , Femenino , Gastrectomía/efectos adversos , Gastrectomía/métodos , Gastrectomía/estadística & datos numéricos , Derivación Gástrica/efectos adversos , Derivación Gástrica/métodos , Derivación Gástrica/estadística & datos numéricos , Humanos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Laparoscopía/estadística & datos numéricos , Líbano/epidemiología , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Obesidad Mórbida/epidemiología , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento , Pérdida de Peso , Adulto Joven
5.
Sci Rep ; 7: 40338, 2017 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-28059138

RESUMEN

Archaeological, palaeontological and geological evidence shows that post-glacial warming released human populations from their various climate-bound refugia. Yet specific connections between these refugia and the timing and routes of post-glacial migrations that ultimately established modern patterns of genetic variation remain elusive. Here, we use Y-chromosome markers combined with autosomal data to reconstruct population expansions from regional refugia in Southwest Asia. Populations from three regions in particular possess distinctive autosomal genetic signatures indicative of likely refugia: one, in the north, centered around the eastern coast of the Black Sea, the second, with a more Levantine focus, and the third in the southern Arabian Peninsula. Modern populations from these three regions carry the widest diversity and may indeed represent the most likely descendants of the populations responsible for the Neolithic cultures of Southwest Asia. We reveal the distinct and datable expansion routes of populations from these three refugia throughout Southwest Asia and into Europe and North Africa and discuss the possible correlations of these migrations to various cultural and climatic events evident in the archaeological record of the past 15,000 years.

6.
Community Ment Health J ; 53(1): 107-116, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-25821928

RESUMEN

The present study aimed to examine the vulnerability to eating disorders (ED) among 949 Lebanese female young adults as well as its association with stress, anxiety, depression, body image dissatisfaction (BID), dysfunctional eating, body mass index, religious affiliation (Christian, Muslim, Druze or Other), religiosity and activity level. Results showed that anxiety had the greatest effect on increasing the predisposition to ED, followed by stress level, BID, depression and restrained eating. Affiliating as Christian was found to significantly decrease the vulnerability to developing an ED. Furthermore, the interaction of anxiety with intrinsic religiosity was found to have a protective role on reducing ED. The current study emphasized a buffering role of intrinsic religiosity against anxiety and ED vulnerability.


Asunto(s)
Susceptibilidad a Enfermedades , Trastornos de Alimentación y de la Ingestión de Alimentos/etiología , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Adolescente , Adulto , Ansiedad , Cristianismo , Estudios Transversales , Femenino , Humanos , Islamismo , Líbano , Factores de Riesgo , Encuestas y Cuestionarios , Adulto Joven
7.
PLoS One ; 11(12): e0168177, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27977735

RESUMEN

Streptococcus pyogenes is a very important human pathogen, commonly associated with skin or throat infections but can also cause life-threatening situations including sepsis, streptococcal toxic shock syndrome, and necrotizing fasciitis. Various studies involving typing and molecular characterization of S. pyogenes have been published to date; however next-generation sequencing (NGS) studies provide a comprehensive collection of an organism's genetic variation. In this study, the genomes of nine S. pyogenes isolates associated with pharyngitis and skin infection were sequenced and studied for the presence of virulence genes, resistance elements, prophages, genomic recombination, and other genomic features. Additionally, a comparative phylogenetic analysis of the isolates with global clones highlighted their possible evolutionary lineage and their site of infection. The genomes were found to also house a multitude of features including gene regulation systems, virulence factors and antimicrobial resistance mechanisms.


Asunto(s)
Faringitis/microbiología , Enfermedades Cutáneas Bacterianas/genética , Infecciones Estreptocócicas/genética , Streptococcus pyogenes/genética , Adulto , Niño , Preescolar , Femenino , Genoma Bacteriano , Humanos , Lactante , Masculino , Persona de Mediana Edad , Enfermedades Cutáneas Bacterianas/microbiología , Infecciones Estreptocócicas/microbiología , Streptococcus pyogenes/aislamiento & purificación , Adulto Joven
8.
J Interprof Care ; 30(2): 165-74, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27026188

RESUMEN

The Lebanese American University Interprofessional Education (LAU IPE) Steps Framework consists of a five-step workshop-based series that is offered throughout the curriculum of health and social care students at an American university in Lebanon. The aim of the present study was to report students' perceptions of their readiness for interprofessional learning before and after completing the IPE steps, their evaluations of interprofessional learning outcomes, as well as their satisfaction with the learning experience as a whole. A longitudinal survey design was used: questionnaires were completed by students before IPE exposure and after each step. The results showed that before IPE exposure, students' perceptions of their readiness for interprofessional learning were generally favourable, with differences across genders (stronger professional identity in females compared to males) and across professions (higher teamwork and collaboration in pharmacy and nutrition students compared to other professions and lower patient centredness in nursing students compared to others). After participation in the IPE steps, students showed enhanced readiness for interprofessional learning and differences between genders and professions decreased. Participants were satisfied with the learning experience and assessment scores showed that all IPE learning outcomes were met. The LAU IPE Steps Framework may be of value to other interprofessional education course developers.


Asunto(s)
Actitud del Personal de Salud , Personal de Salud/educación , Relaciones Interprofesionales , Estudiantes del Área de la Salud/psicología , Competencia Clínica , Conducta Cooperativa , Femenino , Humanos , Líbano , Estudios Longitudinales , Masculino , Atención Dirigida al Paciente/organización & administración , Percepción , Factores Sexuales
9.
Perspect Psychiatr Care ; 52(4): 254-264, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26031192

RESUMEN

PURPOSE: To examine three indicators of psychopathology (stress, anxiety, and depression) as potential moderators of the relationship between body image dissatisfaction (BID) and restrained, emotional, and external eating, while controlling for family-related variables (i.e., household income, living situation, and psychopathology in the family) and individual variables (i.e., body mass index, physical activity, and major life events). DESIGN AND METHODS: A descriptive, correlational cross-sectional design was used. A sample of 894 female undergraduates aged between 18 and 25 completed a self-reported questionnaire. FINDINGS: Moderation analyses indicated that anxiety significantly moderated the relationship between BID and restrained eating, whereas depression and stress did not. PRACTICE IMPLICATIONS: Findings may be used in the development and implementation of education and prevention programs for disordered eating in college campuses. The usefulness of these findings for nursing practice is discussed.


Asunto(s)
Ansiedad/psicología , Imagen Corporal/psicología , Ingestión de Alimentos/psicología , Enfermería Práctica/educación , Autoimagen , Adolescente , Adulto , Estudios Transversales , Depresión/psicología , Conducta Alimentaria , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Femenino , Humanos , Líbano , Modelos Lineales , Escalas de Valoración Psiquiátrica , Autoinforme , Estrés Psicológico/psicología , Adulto Joven
10.
J Clin Exp Neuropsychol ; 38(1): 51-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26588047

RESUMEN

INTRODUCTION: Diagnosis of Parkinson's disease can be emotionally and psychologically challenging to patients. The aim of this study is to investigate the association between Parkinson's disease and depression and the impact of the disease stage and patients' age and gender on this association. METHOD: This is a cross-sectional retrospective study on 200 patients aged above 35 years old from 10 different nationalities. RESULTS: Depression was diagnosed in 46% of the patients enrolled. Most of these patients were treated with an antidepressant. Young age, female gender, and moderate Parkinson's disease stage were found to be significantly associated with depression (odds ratio of 1.19, 1.23, and 1.22, respectively, p < .05). CONCLUSION: This study, the first of its kind in Lebanon and the Middle East and North Africa region, highlights the importance of studying depression in Parkinson's disease and the need for identifying and treating depression symptoms when treating Parkinson's disease patients.


Asunto(s)
Depresión/epidemiología , Enfermedad de Parkinson/epidemiología , Factores de Edad , Anciano , Estudios Transversales , Femenino , Humanos , Líbano/epidemiología , Masculino , Escala del Estado Mental , Persona de Mediana Edad , Valores de Referencia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
11.
Int J Clin Exp Med ; 8(9): 15866-77, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26629090

RESUMEN

BACKGROUND: More evidence is emerging on the strong association between chronic kidney disease (CKD) and cardiovascular disease. We assessed the relationship between coronary artery disease (CAD) and renal dysfunction level (RDL) in a group of Lebanese patients. METHODS: A total of 1268 patients undergoing cardiac catheterization were sequentially enrolled in a multicenter cross sectional study. Angiograms were reviewed and CAD severity scores (CADSS) were determined. Estimated glomerular filtration rate (eGFR) was calculated and clinical and laboratory data were obtained. CKD was defined as eGFR < 60 ml/min. Logistic regression model was performed using multivariate analysis including all traditional risk factors associated with both diseases. ANOVA and the Tukeytestswere used to compare subgroups of patients and to assess the impact of each disease on the severity of the other. RESULTS: Among the 82% patients who exhibited variable degrees of CAD, 20.6% had an eGFR < 60 ml/min. Logistic regression analysis revealed a bidirectional independent association between CAD and CKD with an OR = 2.01 (P < 0.01) and an OR = 1.99 (P < 0.01) for CAD and CKD frequencies, respectively. We observed a steady increase in the CADSS mean as eGFR declined and a progressive reduction in renal function with the worsening of CAD (P < 0.05). This correlation remained highly significant despite considerable inter-patient variability and was at its highest at the most advanced stages of both diseases. CONCLUSIONS: Our results show a strong, independent and graded bidirectional relationship between CAD severity and RDL. We propose to add CAD to the list of risk factors for the development and progression of CKD.

12.
Cell ; 163(2): 456-92, 2015 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-26451489

RESUMEN

UNLABELLED: We present a first-draft digital reconstruction of the microcircuitry of somatosensory cortex of juvenile rat. The reconstruction uses cellular and synaptic organizing principles to algorithmically reconstruct detailed anatomy and physiology from sparse experimental data. An objective anatomical method defines a neocortical volume of 0.29 ± 0.01 mm(3) containing ~31,000 neurons, and patch-clamp studies identify 55 layer-specific morphological and 207 morpho-electrical neuron subtypes. When digitally reconstructed neurons are positioned in the volume and synapse formation is restricted to biological bouton densities and numbers of synapses per connection, their overlapping arbors form ~8 million connections with ~37 million synapses. Simulations reproduce an array of in vitro and in vivo experiments without parameter tuning. Additionally, we find a spectrum of network states with a sharp transition from synchronous to asynchronous activity, modulated by physiological mechanisms. The spectrum of network states, dynamically reconfigured around this transition, supports diverse information processing strategies. PAPERCLIP: VIDEO ABSTRACT.


Asunto(s)
Simulación por Computador , Modelos Neurológicos , Neocórtex/citología , Neuronas/clasificación , Neuronas/citología , Corteza Somatosensorial/citología , Algoritmos , Animales , Miembro Posterior/inervación , Masculino , Neocórtex/fisiología , Red Nerviosa , Neuronas/fisiología , Ratas , Ratas Wistar , Corteza Somatosensorial/fisiología
13.
Br J Ophthalmol ; 99(11): 1460-5, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25926519

RESUMEN

BACKGROUND/AIMS: The goal of this study was to review cataract surgery outcomes at three independent surgery treatment centres established by the UK Specialist Hospitals (UKSH) and to compare these outcomes with recognised benchmarks. METHODS: All patients who underwent cataract surgery at UKSH between July 2005 and March 2013 were included. Complication rates were obtained using annual quality reports, logbooks kept in operating theatres and outpatient departments, and electronic medical records. Refractive outcomes and biometry results between December 2010 and March 2013 were obtained from electronic medical records. Results were compared with previously published benchmarks. RESULTS: This study reviewed 20,070 cataract surgeries. UKSH had lower rates of several operative complications compared with the Cataract National Dataset benchmark study. These included choroidal haemorrhage, hyphaema, intraocular lens complications, iris damage from phacoemulsification, nuclear fragment into the vitreous, phacoemulsification wound burn, posterior capsule rupture or vitreous loss or both, vitreous in anterior chamber, and zonular dialysis. UKSH had lower rates of postoperative complications including corneal decompensation, cystoid macular oedema, iris to wound, posterior capsule opacification with yttrium aluminium garnet indicated, raised intraocular pressure, retained soft lens matter, uveitis, vitreous to section, and wound leak. Biometry outcomes at UKSH were significantly better than recently published benchmarks from the National Healthcare Service. CONCLUSIONS: This is the first large-scale retrospective study of cataract surgery outcomes in the UK independent sector. The results indicate comparable or lower rates for most complications as compared with data collected in a previously published study.


Asunto(s)
Instituciones de Atención Ambulatoria , Extracción de Catarata/normas , Calidad de la Atención de Salud/normas , Agudeza Visual/fisiología , Anciano , Anciano de 80 o más Años , Benchmarking/normas , Biometría , Femenino , Humanos , Complicaciones Intraoperatorias , Implantación de Lentes Intraoculares , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Medicina Estatal , Tomografía de Coherencia Óptica , Reino Unido
14.
Inflamm Res ; 64(6): 415-22, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25902778

RESUMEN

BACKGROUND: The role of inflammation in coronary artery disease (CAD) pathogenesis is well recognized. Moreover, smoking inhalation increases the activity of inflammatory mediators through an increase in leukotriene synthesis essential in atherosclerosis pathogenesis. AIM: The aim of this study is to investigate the effect of "selected" genetic variants within the leukotriene (LT) pathway and other variants on the development of CAD. METHODS: CAD was detected by cardiac catheterization. Logistic regression was performed to investigate the association of smoking and selected susceptibility variants in the LT pathway including ALOX5AP, LTA4H, LTC4S, PON1, and LTA as well as CYP1A1 on CAD risk while controlling for age, gender, BMI, family history, diabetes, hyperlipidemia, and hypertension. RESULTS: rs4769874 (ALOX5AP), rs854560 (PON1), and rs4646903 (CYP1A1 MspI polymorphism) are significantly associated with an increased risk of CAD with respective odds ratios of 1.53703, 1.67710, and 1.35520; the genetic variant rs9579646 (ALOX5AP) is significantly associated with a decreased risk of CAD (OR 0.76163). Moreover, a significant smoking-gene interaction is determined with CYP1A1 MspI polymorphism rs4646903 and is associated with a decreased risk of CAD in current smokers (OR 0.52137). CONCLUSION: This study provides further evidence that genetic variation of the LT pathway, PON1, and CYP1A1 can modulate the atherogenic processes and eventually increase the risk of CAD in our study population. Moreover, it also shows the effect of smoking-gene interaction on CAD risk, where the CYP1A1 MspI polymorphism revealed a decreased risk in current smokers.


Asunto(s)
Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/genética , Inflamación/complicaciones , Inflamación/genética , Fumar/efectos adversos , Fumar/genética , Anciano , Alelos , Arildialquilfosfatasa/genética , Estudios Transversales , Citocromo P-450 CYP1A1/genética , Femenino , Variación Genética , Humanos , Leucotrienos/genética , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo
15.
J Thromb Thrombolysis ; 39(1): 15-22, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24788070

RESUMEN

A main underlying pathology of coronary artery disease is the deposition of cholesterol in the arteries supplying blood to the heart that leads to stenosis and myocardial infarction. We tested if dyslipidemia is a risk factor for coronary artery disease in the Lebanese population, and studied the role of the total cholesterol/HDL cholesterol (TC/HDL-C) ratio as a biological marker of coronary artery disease. We recruited 6,180 Lebanese patients undergoing cardiac catheterization. We conducted a cross-sectional association study between TC/HDL-C ratio and the number and type of vessels occluded in catheterized patients by controlling for confounding effects. The TC/HDL-C ratio ≥4 significantly predicts ≥50 % stenosis in all vessels individually with the odds ratio (OR) ranging from 1.22 to 1.92. The OR increased with increasing number of ≥50 % stenotic vessels (1.39 for 2 vessels and 1.64 for 3-4 vessels), as did risk due to diabetes, CAD family history, gender, and age. The younger than average age of onset subgroup shows a pronounced increase in risk for occlusion of the left main coronary artery due to TC/HDL-C ≥4 (OR 3.26). In conclusion, low levels of HDL-cholesterol and high levels TC/HDL-C ratio are strong biological markers of disease occurrence and severity in the Lebanese population.


Asunto(s)
HDL-Colesterol/sangre , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad
16.
Springerplus ; 3: 533, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25279324

RESUMEN

The onset of coronary artery disease (CAD) is influenced by cardiovascular risk factors that often occur in clusters and may build on one another. The objective of this study is to examine the relationship between hypertension and CAD age of onset in the Lebanese population. This retrospective analysis was performed on data extracted from Lebanese patients (n = 3,753). Logistic regression examined the association of hypertension with the age at CAD diagnosis after controlling for other traditional risk factors. The effect of antihypertensive drugs and lifestyle changes on the onset of CAD was also investigated. Results showed that hypertension is associated with late onset CAD (OR=0.656, 95% CI=0.504-0.853, p=0.001). Use of antihypertensive drugs showed a similar association with delayed CAD onset. When comparing age of onset in CAD patients with traditional risk factors such as hypertension, diabetes, hyperlipidemia, obesity, smoking and family history of CAD, the age of onset was significantly higher for patients with hypertension compared to those with any of the other risk factors studied (p < 0.001). In conclusion, hypertension and its treatment are associated with late coronary atherosclerotic manifestations in Lebanese population. This observation is currently under investigation to clarify its genetic and/or environmental mechanisms.

17.
Front Behav Neurosci ; 7: 88, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23898245

RESUMEN

Autism is a neurodevelopmental condition diagnosed by impaired social interaction, abnormal communication and, stereotyped behaviors. While post-mortem and imaging studies have provided good insights into the neurobiological symptomology of autism, animal models can be used to study the neuroanatomical, neurophysiological and molecular mediators in more detail and in a more controlled environment. The valproic acid (VPA) rat model is an environmentally triggered model with strong construct and clinical validity. It is based on VPA teratogenicity in humans, where mothers who are medicated with VPA during early pregnancy show an increased risk for giving birth to an autistic child. In rats, early embryonic exposure, around the time of neural tube closure, leads to autism-like anatomical and behavioral abnormalities in the offspring. Considering the increasing use of the VPA rat model, we present our observations of the general health of Wistar dams treated with a single intraperitoneal injection of 500 or, 600 mg/kg VPA on embryonic day E12.5, as well as their male and female offspring, in comparison to saline-exposed controls. We report increased rates of complete fetal reabsorption after both VPA doses. VPA 500 mg/kg showed no effect on dam body weight during pregnancy or, on litter size. Offspring exposed to VPA 500 mg/kg showed smaller brain mass on postnatal days 1 (P1) and 14 (P14), in addition to abnormal nest seeking behavior at P10 in the olfactory discrimination test, relative to controls. We also report increased rates of physical malformations in the offspring, rare occurrences of chromodacryorrhea and, developmentally similar body mass gain. Further documentation of developmental health may guide sub-grouping of individuals in a way to better predict core symptom severity.

18.
PLoS One ; 8(1): e54616, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23382925

RESUMEN

The Middle East was a funnel of human expansion out of Africa, a staging area for the Neolithic Agricultural Revolution, and the home to some of the earliest world empires. Post LGM expansions into the region and subsequent population movements created a striking genetic mosaic with distinct sex-based genetic differentiation. While prior studies have examined the mtDNA and Y-chromosome contrast in focal populations in the Middle East, none have undertaken a broad-spectrum survey including North and sub-Saharan Africa, Europe, and Middle Eastern populations. In this study 5,174 mtDNA and 4,658 Y-chromosome samples were investigated using PCA, MDS, mean-linkage clustering, AMOVA, and Fisher exact tests of F(ST)'s, R(ST)'s, and haplogroup frequencies. Geographic differentiation in affinities of Middle Eastern populations with Africa and Europe showed distinct contrasts between mtDNA and Y-chromosome data. Specifically, Lebanon's mtDNA shows a very strong association to Europe, while Yemen shows very strong affinity with Egypt and North and East Africa. Previous Y-chromosome results showed a Levantine coastal-inland contrast marked by J1 and J2, and a very strong North African component was evident throughout the Middle East. Neither of these patterns were observed in the mtDNA. While J2 has penetrated into Europe, the pattern of Y-chromosome diversity in Lebanon does not show the widespread affinities with Europe indicated by the mtDNA data. Lastly, while each population shows evidence of connections with expansions that now define the Middle East, Africa, and Europe, many of the populations in the Middle East show distinctive mtDNA and Y-haplogroup characteristics that indicate long standing settlement with relatively little impact from and movement into other populations.


Asunto(s)
Cromosomas Humanos Y , Grupos de Población Continentales/genética , ADN Mitocondrial/genética , África , Análisis por Conglomerados , Europa (Continente) , Frecuencia de los Genes , Genética de Población , Haplotipos , Humanos , Medio Oriente , Filogenia , Filogeografía , Polimorfismo de Nucleótido Simple
19.
PLoS One ; 7(6): e38663, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22745674

RESUMEN

The manifestation of coronary artery disease (CAD) follows a well-choreographed series of events that includes damage of arterial endothelial cells and deposition of lipids in the sub-endothelial layers. Genome-wide association studies (GWAS) of multiple populations with distinctive genetic and lifestyle backgrounds are a crucial step in understanding global CAD pathophysiology. In this study, we report a GWAS on the genetic basis of arterial stenosis as measured by cardiac catheterization in a Lebanese population. The locus of the phosphatase and actin regulator 1 gene (PHACTR1) showed association with coronary stenosis in a discovery experiment with genome wide data in 1,949 individuals (rs9349379, OR = 1.37, p = 1.57×10(-5)). The association was replicated in an additional 2,547 individuals (OR = 1.31, p = 8.85×10(-6)), leading to genome-wide significant association in a combined analysis (OR = 1.34, p = 8.02×10(-10)). Results from this GWAS support a central role of PHACTR1 in CAD susceptibility irrespective of lifestyle and ethnic divergences. This association provides a plausible component for understanding molecular mechanisms involved in the formation of stenosis in cardiac vessels and a potential drug target against CAD.


Asunto(s)
Estenosis Coronaria/genética , Estudio de Asociación del Genoma Completo/métodos , Proteínas de Microfilamentos/genética , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Líbano , Polimorfismo de Nucleótido Simple/genética
20.
PLoS One ; 7(4): e34786, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22509357

RESUMEN

The electrical diversity of neurons arises from the expression of different combinations of ion channels. The gene expression rules governing these combinations are not known. We examined the expression of twenty-six ion channel genes in a broad range of single neocortical neuron cell types. Using expression data from a subset of twenty-six ion channel genes in ten different neocortical neuronal types, classified according to their electrophysiological properties, morphologies and anatomical positions, we first developed an incremental Support Vector Machine (iSVM) model that prioritizes the predictive value of single and combinations of genes for the rest of the expression pattern. With this approach we could predict the expression patterns for the ten neuronal types with an average 10-fold cross validation accuracy of 87% and for a further fourteen neuronal types not used in building the model, with an average accuracy of 75%. The expression of the genes for HCN4, Kv2.2, Kv3.2 and Caß3 were found to be particularly strong predictors of ion channel gene combinations, while expression of the Kv1.4 and Kv3.3 genes has no predictive value. Using a logic gate analysis, we then extracted a spectrum of observed combinatorial gene expression rules of twenty ion channels in different neocortical neurons. We also show that when applied to a completely random and independent data, the model could not extract any rules and that it is only possible to extract them if the data has consistent expression patterns. This novel strategy can be used for predictive reverse engineering combinatorial expression rules from single-cell data and could help identify candidate transcription regulatory processes.


Asunto(s)
Regulación de la Expresión Génica , Canales Iónicos/metabolismo , Neuronas/citología , Neuronas/metabolismo , Animales , Redes Reguladoras de Genes , Canales Iónicos/genética , Neocórtex/citología , Neocórtex/metabolismo , Ratas , Máquina de Vectores de Soporte
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