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Understanding the intracellular dynamics of brain cells entails performing three-dimensional molecular simulations incorporating ultrastructural models that can capture cellular membrane geometries at nanometer scales. While there is an abundance of neuronal morphologies available online, e.g. from NeuroMorpho.Org, converting those fairly abstract point-and-diameter representations into geometrically realistic and simulation-ready, i.e. watertight, manifolds is challenging. Many neuronal mesh reconstruction methods have been proposed; however, their resulting meshes are either biologically unplausible or non-watertight. We present an effective and unconditionally robust method capable of generating geometrically realistic and watertight surface manifolds of spiny cortical neurons from their morphological descriptions. The robustness of our method is assessed based on a mixed dataset of cortical neurons with a wide variety of morphological classes. The implementation is seamlessly extended and applied to synthetic astrocytic morphologies that are also plausibly biological in detail. Resulting meshes are ultimately used to create volumetric meshes with tetrahedral domains to perform scalable in silico reaction-diffusion simulations for revealing cellular structure-function relationships. Availability and implementation: Our method is implemented in NeuroMorphoVis, a neuroscience-specific open source Blender add-on, making it freely accessible for neuroscience researchers., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: With the continuous spread and emergence of transmissible diseases, focusing on preventive measures is essential to decrease their incidence and spread. In addition to behavioral measures, vaccination is an optimal way to protect the population and eradicate infectious diseases. The majority are aware of children's vaccinations, while many might not know that adult vaccinations are also essential., Objectives: This study aims to understand the perception of Lebanese adults towards vaccination and their knowledge and awareness of its importance. This is a national cross-sectional study, conducted between January 2020 and January 2021., Results: the data were collected from 1023 subjects, the majority being Lebanese, previously healthy, and with a graduate or post-graduate level of education. Out of these participants, 44.9% were advised to take vaccines, half of them by healthcare workers. The most common vaccine received during adult life is the Flu vaccine. Overall, 25.6% of the participants were unaware that they needed vaccines and 27.9% thought it is not indicated. Participants' knowledge about vaccination is variable. In total, 39.4% agree or are uncertain whether vaccines contain harmful chemicals and 48.4% believe that vaccines will trigger diseases. The level of education and occupation significantly enhances knowledge about vaccination. Some participants 27.3% are concerned about the vaccine's side effects. The group of young participants, graduates, and nonsmokers think that the vaccine is a necessity and had a positive attitude towards vaccination., Conclusions: Many Lebanese lack knowledge about adult vaccination protection and its benefits in the community. It is essential that the country's health ministry department collaborate with the healthcare system to launch awareness campaigns about adult vaccination in the country to overcome the barriers and ensure better coverage.

The world has been dealing with the SARS-COV-2 pandemic since December 2019 and a lot of effort has focused on tracking the spread of the virus by gathering information regarding testing statistics and generating viral genomic sequences. Unfortunately, there is neither a single comprehensive resource with global historical testing data nor a centralized database with summary statistics of the identified genomic variants. We merged different pre-aggregated historical testing data and complemented them with our manually extracted ones, which consist of 6852 historical test statistics from 76 countries/states unreported in any other dataset, at the date of submission, making our dataset the most comprehensive to date. We also analyzed all publicly deposited SARS-CoV-2 genomic sequences in GISAID and annotated their variants. Both datasets can be accessed through our interactive dashboard which also provides important insights on different outbreak trends across countries and states. The dashboard is available at https://bioinfo.lau.edu.lb/gkhazen/covid19 . A daily updated version of the datasets can be downloaded from github.com/KhazenLab/covid19-data., (© 2022. The Author(s).)

Data comparing the occurrence of gastroesophageal cancer after gastric bypass procedures are lacking and are only available in the form of case reports. We perform in this study a systematic review and a meta-analysis of all the reported cases of gastroesophageal cancer following Roux-en-Y gastric bypass (RYGB) and loop gastric bypass-one anastomosis gastric bypass/mini gastric bypass (LGB-OAGB/MGB). We conducted a systematic review of all the reported cases in articles referenced in PubMed/Medline, Cochrane, and Scholar Google. Only cases of gastro-esophageal adenocarcinoma following RYGB or LGB-OAGB/MGB are included. Statistical analysis was done accordingly. Fifty cases were identified, along with 2 reported in this paper. Sixty-one percent (27/44) of the cancers after RYGB were in the gastric tube compared to 37.5% (3/8) after LGB-OAGB/MGB. This resulted in an odds ratio of 0.38 (p-value = 0.26), which failed to prove an increase in cancer occurrence in the gastric tube after LGB-MGB/OAGB compared to RYGB. The most common symptoms were dysphagia for cancers occurring in the gastric tube (15/30) and abdominal pain for those occurring in the excluded stomach (10/22). Twenty-nine/thirty of the cancers in the gastric tube were diagnosed by gastroscopy and 13/22 of the cancers in the excluded stomach were diagnosed by CT scan. Gastroesophageal cancers after gastric bypass procedures occur commonly in the excluded stomach where many are not identified by conventional means. Physician awareness and patient education as well as lifelong follow-up are essential for maintaining bypass surgeries on the beneficial side., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The World Health Organization has promoted the use of serological testing as a rapid and accurate technique for the detection of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In Lebanon, a better understanding of the immune response against SARS-CoV-2 is needed to develop effective measures for prevention and to plan an appropriate national vaccination program. This study aimed to measure the immunity status in Lebanon., Methods: In this cross-sectional study, the population comprised male and female Lebanese and non-Lebanese residents of Lebanon between the ages 15 and 75. The exclusion criteria included: same household, symptomatic individuals, and extremes of age (< 15 and > 75). Representative testing for SARS-CoV-2 antibodies (anti-SARS-CoV-2 electrochemiluminescence immunoassay/ECLIA) was used to assess the prevalence of SARS-CoV-2 infection in Lebanon., Results: In total, 13 755 participants were recruited over a 6-month period. Of these, 3168 (23.03%) individuals tested positive for anti-SARS-CoV-2, with levels of positivity varying among districts. A higher level of seropositivity was detected in the female participants., Conclusion: Seroprevalence against SARS-CoV-2 varied within Lebanon, but was comparable to the levels reported in the MENA region at the time of the study. The seroprevalence documented in this study represents a level of immunity that is not protective at the national level., Funding: This study was funded by the Lebanese American University School of Medicine., (© 2022 The Author(s).)

Objective: Diabetes self-management education (DSME) is an essential component of lifestyle management needed for diabetes care. This pilot-study tested the effect of culturally-tailored education targeting diabetes selfcare on glycemia and cardiovascular risk factors of Lebanese with type 2 diabetes mellitus (T2DM) (n = 27; Age: 61 ± 10 yrs, 59% males, HbA1c: 8.98 ± 1.38%)., Results: Diabetes self-care (Diet, Self-Monitoring Blood Glucose and foot care) improved after 6 months, which was reflected in a significant drop in glycemic levels (HbA1c:-0.5%; FPG: - 38 mg/dl), and cholesterol/HDL ratio (4.45 ± 1.39 vs. 4.06 ± 1.29). Waist circumference decreased at 6 months compared to 3 months (p < 0.05). This is the first effective culturally-tailored intervention that improved self-care, glycemic control, body adiposity and lipid profile of Lebanese with T2DM. Larger scale implementation with representative sample is warranted., (© 2022. The Author(s).)

Because of their considerable number and diversity, membrane proteins and their macromolecular complexes represent the functional units of cells. Their quaternary structure may be stabilized by interactions between the α-helices of different proteins in the hydrophobic region of the cell membrane. Membrane proteins equally represent potential pharmacological targets par excellence for various diseases. Unfortunately, their experimental 3D structure and that of their complexes with other intramembrane protein partners are scarce due to technical difficulties. To overcome this key problem, we devised PPIMem, a computational approach for the specific prediction of higher-order structures of α-helical transmembrane proteins. The novel approach involves proper identification of the amino acid residues at the interface of molecular complexes with a 3D structure. The identified residues compose then nonlinear interaction motifs that are conveniently expressed as mathematical regular expressions. These are efficiently implemented for motif search in amino acid sequence databases, and for the accurate prediction of intramembrane protein-protein complexes. Our template interface-based approach predicted 21,544 binary complexes between 1,504 eukaryotic plasma membrane proteins across 39 species. We compare our predictions to experimental datasets of protein-protein interactions as a first validation method. The online database that results from the PPIMem algorithm with the annotated predicted interactions are implemented as a web server and can be accessed directly at https://transint.univ-evry.fr., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Purpose: Surgeons management of osteochondral lesions of the talus (OLT) may be different to the published guidelines because not all treatment recommendations are feasible in every country. This study aimed to assess how OLT are managed worldwide by foot and ankle surgeons., Methods: A web-based survey was distributed to the members of 21 local and international scientific societies focused on foot and ankle or sports medicine surgery. Answers with a prevalence greater than 75% of respondents were considered a "main tendency", whereas where prevalence exceeded 50% of respondents they were considered a "tendency"., Results: A total of 1804 surgeons from 79 different countries returned the survey. The responses to 19 of 28 questions (68%) regarding management and treatment of OLT achieved a main tendency (> 75%) or a tendency (> 50%). Symptoms reported to be most suspicious for OLT were pain on weight-bearing (WB) and after activity (83%), deep localization of the pain (62%), and any history of trauma (55%). 89% of surgeons routinely obtain an MRI, 72% routinely get WB radiographs, and 50% perform a CT scan. When treated surgically, OLTs are managed in isolation by only 7% of surgeons, and combined with ligament repair or reconstruction by 79%; 67% report simultaneous excision of soft-tissue or bony impingements (64%). For lesions less than 10-15 mm in diameter, bone marrow stimulation (BMS) represents the first choice of treatment for 78% of surgeons (main tendency). No other treatment was recorded as a tendency. For lesions greater than 15 mm in diameter no tendencies were recorded. The BMS represented the most preferred treatment being the first choice of treatment for 41% of surgeons. OLT depth had little influence on treatment choice: 71% of surgeons treating small lesions and 69% treating large lesions would choose the same treatment regardless of whether the lesion had a depth lesser or greater than 5 mm., Conclusion: The management of OLT by foot and ankle surgeons from around the world remains extremely varied. The main clinical relevance of this study is that it provides updated information with regard to the management of OLT internationally, which could be used by surgeons worldwide in their decision-making and to inform the patient about available surgical options., Level of Evidence: Level IV.

Background: Candida bloodstream infection (BSI) remains one of the leading causes of BSI in critically ill and immunosuppressed cancer patients. In light of the changing epidemiology and rising resistant species, duration of treatment and appropriate timing of stepdown therapy from intravenous (IV) to oral antifungal agents are crucial for utmost disease control and overall survival., Method: We performed a multicenter retrospective study, with 119 non-neutropenic patients enrolled from four different medical institutions in Brazil, Lebanon, Spain and the United States, to assess the duration of IV therapy and appropriate time to step-down to oral therapy in adult patients, 14 years of age and older, with documented candidemia. The analysis was done using the statistical program R and SAS v9.4. Descriptive statistics are presented as frequencies and tables and the Fisher exact test was used to test the association between the categorical variables: organism, cancer, country, antifungal drug and duration of therapy, and time of step-down., Results: Candida albicans contributed to 45% of bloodstream infection versus 55% of infection caused by Candida non-albicans. The three most common Candida non-albicans are: Candida glabrata 24%, Candida parapsilosis 13% and Candida tropicalis 8%. Most (57%) of the patients were admitted to ICU, whereas 52% had underlying malignancy. Multivariate analysis showed that a stay at ICU or an underlying cancer requiring chemotherapy were independently associated with failure and death (p <0.001). The average total duration of therapy was 14 days in all patients and 16 days in those who responded and survived. Forty-five patients were stepped down to either fluconazole and/or voriconazole in association with clinical and microbiologic resolution of the candidemia. The average (and median) day of step-down was 5 days. Patients who had a stepdown had more favorable outcomes (78% survival) as compared to those with no stepdown (56% survival) (P = 0.022). However, the 20 patients who received 1-4 days of first IV treatment before a stepdown to oral azoles had a comparable outcome (20% mortality) to the 25 patients who received >5 days of treatment (24% mortality - p = 0.75)., Conclusion: Our data support the IDSA guidelines in that the total duration of treatment for candidemia should be at least 14 days after a negative blood culture. However, in non-neutropenic cancer patients with candidemia, a step-down to oral azole therapy can safely take place early (within 4 days of initiating IV therapy) as long as the patient had clinical and microbiologic resolution of the bloodstream infections., Competing Interests: Competing interests: Dr. Ray Hachem serves on the board of Worldwide Institute for Medical Education (WIME). Dr. Issam Raad gave a talk in 2020 in CME conference sponsored by Pfizer.

Objectives: CYP3A5 and ABCB1 are highly implicated in the pharmacokinetics and pharmacodynamics of immunosuppressive agents, such as calcineurin inhibitors and mammalian target of rapamycin inhibitors. The polymorphisms of their coding genes play important roles in the interindividual and intraindividual differences of bioavailability of these drugs. In this study, our objective was to investigate, in a Lebanese population,the frequency of ABCB1C3435T (rs1045642) and CYP3A5*3 (rs776746) polymorphisms and to compare the results to preexisting data from other populations., Materials and Methods: We determined the frequencies of the allelic variants of interest for 1824 Lebanese participants, and we compared these results with those from other major ethnic groups., Results: The allelic frequencies were 91.4% (C) and 8.6% (T) for CYP3A5*3 and 50.8% (T) and 49.2% (C) for ABCB1 C3435T. Our results were significantly different from most other world populations, except the European population., Conclusions: The frequencies of gene variants of interest in our Lebanese population were similar to those found in European populations. Most of our study population were CYP3A5*3 carriers, and more than half may have a lower P-glycoprotein efflux pump. These characteristics might render Lebanese transplant recipients more prone to the development of drug toxicity and in need of lower drug doses.

Background: Coronary Artery Disease (CAD) is the narrowing or blockage of the coronary arteries. It is closely associated with numerous genetics and environmental factors that have been extensively evaluated in various populations. In recent studies, severe phenotypes have been strongly linked to genetic risk factors., Methods: This study investigated the association of clinical, demographic, and genetic factors with severe coronary artery stenosis phenotypes in our population composed of 1734 individuals with severe coronary stenosis (≥ 50% in coronary vessels) and comparing them to 757 controls with no evidence of stenosis on angiography. We performed generalized linear model (GLM) genome-wide association studies to evaluate three stratification models and their associations to characteristics of the clinical disease. In model 1, patients were not stratified. In model 2, patients were stratified based on presence or absence of CAD family history (FxCAD). In model 3, patients were stratified by young age of CAD onset., Results: Eight SNPs (single nucleotide polymorphism) were significantly associated with severe CAD phenotypes in the various models [Formula: see text], four of these SNPs were associated with severe CAD and the four others were specifically significant for young CAD patients. While these SNPs were not previously reported for association with CAD, six of them are present in genes that have already been linked to coronary disease., Conclusion: In conclusion, this study presents new genetic factors associated with severe stenosis and highlights different risk factors associated with a young age at diagnosis of CAD.

Displaced intra-articular calcaneal fractures are among the most difficult articular fractures to treat, with a high rate of potential complications. Is important to restore calcaneus posterior facet anatomy as well as calcaneus width, length, and height. The extensile lateral approach provides excellent fracture visualization and allows reduction of the displaced fracture fragments, but high complication rate has been described with this approach, so many studies favor the sinus tarsi approach. Recent evidence favoring sinus tarsi rather than the extensile lateral approach has shifted opinion toward this less invasive approach, which can be considered the new gold standard., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aortic valve stenosis (AVS) is a prevalent condition among the elderly population that eventually requires aortic valve replacement. The lack of reliable biomarkers for AVS poses a challenge for its early diagnosis and the application of preventive measures. Untargeted gas chromatography mass spectrometry (GC-MS) metabolomics was applied in 46 AVS cases and 46 controls to identify plasma and urine metabolites underlying AVS risk. Multivariate data analyses were performed on pre-processed data (e.g. spectral peak alignment), in order to detect changes in metabolite levels in AVS patients and to evaluate their performance in group separation and sensitivity of AVS prediction, followed by regression analyses to test for their association with AVS. Through untargeted analysis of 190 urine and 130 plasma features that could be detected and quantified in the GC-MS spectra, we identified contrasting levels of 22 urine and 21 plasma features between AVS patients and control subjects. Following metabolite assignment, we observed significant changes in the concentration of known metabolites in urine (n = 14) and plasma (n = 15) that distinguish the metabolomic profiles of AVS patients from healthy controls. Associations with AVS were replicated in both plasma and urine for about half of these metabolites. Among these, 2-Oxovaleric acid, elaidic acid, myristic acid, palmitic acid, estrone, myo-inositol showed contrasting trends of regulation in the two biofluids. Only trans-Aconitic acid and 2,4-Di-tert-butylphenol showed consistent patterns of regulation in both plasma and urine. These results illustrate the power of metabolomics in identifying potential disease-associated biomarkers and provide a foundation for further studies towards early diagnostic applications in severe heart conditions that may prevent surgery in the elderly., Competing Interests: The authors have declared that no competing interests exist.

Background: Finding combinations of homotypic or heterotypic genomic sites obeying a specific grammar in DNA sequences is a frequent task in bioinformatics. A typical case corresponds to the identification of cis-regulatory modules characterized by a combination of transcription factor binding sites in a defined window size. Although previous studies identified clusters of genomic sites in species with varying genome sizes, the availability of a dedicated and versatile tool to search for such clusters is lacking., Results: We present fcScan, an R/Bioconductor package to search for clusters of genomic sites based on user defined criteria including cluster size, inter-cluster distances and sites order and orientation allowing users to adapt their search criteria to specific biological questions. It supports GRanges, data frame and VCF/BED files as input and returns data in GRanges format. By performing clustering on vectorized data, fcScan is adapted to search for genomic clusters in millions of sites as input in short time and is thus ideal to scan data generated by high throughput methods including next generation sequencing., Conclusions: fcScan is ideal for detecting cis-regulatory modules of transcription factor binding sites with a specific grammar as well as genomic loci enriched for mutations. The flexibility in input parameters allows users to perform searches targeting specific research questions. It is released under Artistic-2.0 License. The source code is freely available through Bioconductor (https://bioconductor.org/packages/fcScan) and GitHub (https://github.com/pkhoueiry/fcScan).

Background: Medication overuse headache (MOH) is a chronic pain syndrome that arises from the frequent use of acute antimigraine drugs. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique with a possible therapeutic effect in this particular context., Methods: This was a randomized, sham-controlled, cross-over study. Eighteen patients with MOH (17 women, age range: 20-38 years) received three sets of three consecutive daily sessions of tDCS: anodal tDCS over the prefrontal cortex, cathodal tDCS over the occipital cortex ipsilateral to the dominant side of migraine pain, and sham. The order in which the tDCS blocks were delivered was randomly defined based on a 1:1:1 ratio. Patients filled in a migraine diary that allowed recording of the pain intensity (visual analogue scale) and the daily consumption of analgesic pills from one week before to two weeks after each condition., Results: Both prefrontal and occipital tDCS lowered the total number of migraine days and the number of severe migraine days per week at week 1, but only the effects of occipital tDCS on these two outcomes lasted until week 2. Only occipital tDCS decreased the daily analgesic pills consumption, at weeks 1 and 2., Conclusion: Three consecutive days of cathodal occipital tDCS appear to improve the clinical outcomes in patients with MOH.

Three consecutive daily sessions of cathodal transcranial direct current stimulation (tDCS) was sufficient to show a significant decrease in headache duration and intensity as well as tablets consumption, in patients suffering from episodic migraine., Background: Migraine prophylaxis is recommended in patients with frequent and/or intense headaches, but poor tolerability and lack of efficacy of preventive drugs are common in clinical practice. Hence, new prophylactic strategies are needed., Objective: The aim of this study was to evaluate the efficacy of tDCS in terms of migraine prophylaxis., Methods: This was a double blind and sham-controlled trial. Forty-two migraine patients were randomly assigned in a crossover design to receive three consecutive daily sessions of both sham and cathodal tDCS stimulation (2.0 mA, 20 min) over the occipital cortex of the dominant side of the migraine pain (O1/O2). Migraine duration and intensity, number of analgesic tablets, and number of headache-free days (where no headache abortive medications are taken) were recorded one week before and two weeks after treatment. A washout period of one week was allowed before crossing to the other treatment arm., Results: Relative to sham, cathodal stimulation was associated with a significant reduction in the number of headache days, tablets consumption, and pain intensity; and a significant increase in the number of headache-free days. These beneficial effects were sustained over two weeks. No serious side effects were observed, and the procedure was well tolerated., Conclusion: Based on these findings, cathodal tDCS applied to the occipital cortex seems to be an effective and well tolerated alternative to pharmacotherapy in patients with episodic migraine.

Background: Most multiple sclerosis (MS) patients will develop walking limitations during the disease. Sustained-release oral fampridine is the only approved drug that will improve gait in a subset of MS patients. Objectives: (1) Evaluate fampridine cortical excitability effect in MS patients with gait disability. (2) Investigate whether cortical excitability changes can predict the therapeutic response to fampridine. Method: This prospective observational study enrolled 20 adult patients with MS and gait impairment planned to receive fampridine 10 mg twice daily for two consecutive weeks. Exclusion criteria included: Recent relapse (<3 months), modification of disease modifying drugs (<6 months), or Expanded Disability Status Scale (EDSS) score >7. Neurological examination, timed 25-foot walk test (T25wt), EDSS, and cortical excitability studies were performed upon inclusion and 14 days after initiation of fampridine. Results: After treatment, the mean improvement of T25wt (ΔT25wt) was 4.9 s. Significant enhancement of intra-cortical facilitation was observed (139% versus 241%, p = 0.01) following treatment. A positive correlation was found between baseline resting motor threshold (rMT) and both EDSS ( r = 0.57; p < 0.01) and ΔT25wt ( r = 0.57, p = 0.01). rMT above 52% of the maximal stimulator output was found to be a good predictor of a favorable response to fampridine (accuracy: 75%). Discussion: Fampridine was found to have a significant modulatory effect on the cerebral cortex, demonstrated by an increase in excitatory intracortical processes as unveiled by paired-pulse transcranial magnetic stimulation. rMT could be useful in selecting patients likely to experience a favorable response to fampridine.

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., Competing Interests: The authors have declared that no competing interests exist.

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.

Childhood neuroblastoma is one of the most common types of extra-cranial cancer affecting children with a clinical spectrum ranging from spontaneous regression to malignant and fatal progression. In order to improve the clinical outcomes of children with high-risk neuroblastoma, it is crucial to understand the tumorigenic mechanisms that govern its malignant behaviors. MYCN proto-oncogene, bHLH transcription factor (MYCN) amplification has been implicated in the malignant, treatment-evasive nature of aggressive, high-risk neuroblastoma. In this study, we used a SILAC approach to compare the proteomic signatures of MYCN-amplified IMR-32 and non-MYCN-amplified SK-N-SH human neuroblastoma cells. Tumorigenic proteins, including fatty-acid binding protein 5 (FABP5), L1-cell adhesion molecule (L1-CAM), baculoviral IAP repeat containing 5 [BIRC5 (survivin)] and high mobility group protein A1 (HMGA1) were found to be significantly upregulated in the IMR-32 compared to the SK-N-SH cells and mapped to highly tumorigenic pathways including, MYC, MYCN, microtubule associated protein Tau (MAPT), E2F transcription factor 1 (E2F1), sterol regulatory element binding transcription factor 1 or 2 (SREBF1/2), hypoxia-inducible factor 1α (HIF-1α), Sp1 transcription factor (SP1) and amyloid precursor protein (APP). The transcriptional knockdown (KD) of MYCN, HMGA1, FABP5 and L1-CAM significantly abrogated the proliferation of the IMR-32 cells at 48 h post transfection. The early apoptotic rates were significantly higher in the IMR-32 cells in which FABP5 and MYCN were knocked down, whereas cellular migration was significantly abrogated with FABP5 and HMGA1 KD compared to the controls. Of note, L1-CAM, HMGA1 and FABP5 KD concomitantly downregulated MYCN protein expression and MYCN KD concomitantly downregulated L1-CAM, HMGA1 and FABP5 protein expression, while survivin protein expression was significantly downregulated by MYCN, HMGA1 and FABP5 KD. In addition, combined L1-CAM and FABP5 KD led to the concomitant downregulation of HMGA1 protein expression. On the whole, our data indicate that this inter-play between MYCN and the highly tumorigenic proteins which are upregulated in the malignant IMR-32 cells may be fueling their aggressive behavior, thereby signifying the importance of combination, multi-modality targeted therapy to eradicate this deadly childhood cancer.

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.

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.

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.

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., Competing Interests: The authors have declared that no competing interests exist.

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., (© 2015 Wiley Periodicals, Inc.)

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.

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.

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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.

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.

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.

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.

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.

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.

Stage I PTTD was defined by Johnson and Strom as tenosynovitis or tendinitis whereby tendon length remains normal, there is no hindfoot deformity, and diagnosis is basically clinical, characterized by swelling and tenderness posterior to the medial malleolus. The PTT has a hypovascular zone 40 mm proximal to the insertion of the tendon and 14 mm in length. Pain often is localized to this portion of the tendon. Tendon power might be normal, and the patient can perform single heel rise, sometimes with slight discomfort. This condition is often misdiagnosed as ankle sprain, which delays correct diagnosis and early treatment that may improve symptoms, stop the disease process, and prevent the development of adult acquired flatfoot deformity. Ultrasonography is a valuable adjunctive diagnostic tool for stage I PTTD, but the authors always indicate MRI for accurate diagnosis in such patients. Patients with stage I PTTD are first treated nonoperatively with nonsteroidal anti-inflammatory drugs for 5 days, cryotherapy, local ultrasound, and a PTTD airlift brace (Aircast) for 3 to 6 months. If symptoms persist, surgical debridement and synovectomy has been suggested. PTT tendoscopic synovectomy is a minimally invasive and effective surgical procedure to treat patients with stage I PTTD. It has the advantages of less wound pain, and fewer scar and wound problems. If tendon tear is observed during tendoscopy, it must be repaired with nonabsorbable sutures using a 3- or 4-cm incision., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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.

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 Caβ3 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.

Ion channels are membrane proteins that selectively conduct ions across the cell membrane. The flux of ions through ion channels drives electrical and biochemical processes in cells and plays a critical role in shaping the electrical properties of neurons. During the past three decades, extensive research has been carried out to characterize the molecular, structural, and biophysical properties of ion channels. This research has begun to elucidate the role of ion channels in neuronal function and has subsequently led to the development of computational models of ion channel function. Although there have been substantial efforts to consolidate these findings into easily accessible and coherent online resources, a single comprehensive resource is still lacking. The success of these initiatives has been hindered by the sheer diversity of approaches and the variety in data formats. Here, we present "Channelpedia" (http://channelpedia.net), which is designed to store information related to ion channels and models and is characterized by an efficient information management framework. Composed of a combination of a database and a wiki-like discussion platform Channelpedia allows researchers to collaborate and synthesize ion channel information from literature. Equipped to automatically update references, Channelpedia integrates and highlights recent publications with relevant information in the database. It is web based, freely accessible and currently contains 187 annotated ion channels with 45 Hodgkin-Huxley models.

Genome wide association studies (GWAS) and their replications that have associated DNA variants with myocardial infarction (MI) and/or coronary artery disease (CAD) are predominantly based on populations of European or Eastern Asian descent. Replication of the most significantly associated polymorphisms in multiple populations with distinctive genetic backgrounds and lifestyles is crucial to the understanding of the pathophysiology of a multifactorial disease like CAD. We have used our Lebanese cohort to perform a replication study of nine previously identified CAD/MI susceptibility loci (LTA, CDKN2A-CDKN2B, CELSR2-PSRC1-SORT1, CXCL12, MTHFD1L, WDR12, PCSK9, SH2B3, and SLC22A3), and 88 genes in related phenotypes. The study was conducted on 2,002 patients with detailed demographic, clinical characteristics, and cardiac catheterization results. One marker, rs6922269, in MTHFD1L was significantly protective against MI (OR=0.68, p=0.0035), while the variant rs4977574 in CDKN2A-CDKN2B was significantly associated with MI (OR=1.33, p=0.0086). Associations were detected after adjustment for family history of CAD, gender, hypertension, hyperlipidemia, diabetes, and smoking. The parallel study of 88 previously published genes in related phenotypes encompassed 20,225 markers, three quarters of which with imputed genotypes The study was based on our genome-wide genotype data set, with imputation across the whole genome to HapMap II release 22 using HapMap CEU population as a reference. Analysis was conducted on both the genotyped and imputed variants in the 88 regions covering selected genes. This approach replicated HNRNPA3P1-CXCL12 association with CAD and identified new significant associations of CDKAL1, ST6GAL1, and PTPRD with CAD. Our study provides evidence for the importance of the multifactorial aspect of CAD/MI and describes genes predisposing to their etiology., (© 2011 Saade et al.)

Coronary artery disease (CAD) is a complex disease with various components, genetic as well as environmental. Previous reports correlating ALOX5AP gene variants and CAD showed conflicting results depending on the population studied. In this study, we examined the contribution of ALOX5AP genetic predisposition to CAD in a group of CAD patients and controls carefully selected from the Lebanese population. We genotyped SNPs for ALOX5AP variants in 289 catheterized patients aged ≤52 years with >50% stenosis in at least one main coronary artery and 227 catheterized control subjects aged 60 years and above with 0% stenosis. Chi-square (χ (2)) tests and logistic regression showed no significant difference in the allele and genotype frequencies between the CAD or myocardial infarction (MI) cases and the healthy controls. Haplotype analysis using PHASE showed that the distribution of the risk haplotypes among cases and controls were not significantly different and had no attributable risk to CAD (P = 1.00 and P = 0.5, respectively) or MI (P = 0.2 and P = 0.5, respectively). Our data revealed that ALOX5AP gene variants are not predictors of CAD risk or MI risk among Lebanese patients.

Genotypic profiles of the natural killer cell immunoglobulin-like receptors (KIR) have been reported to vary among different ethnic groups and variable clinical entities. This study represents the first report on its distribution among patients with familial Mediterranean fever (FMF). We studied 56 unrelated Lebanese FMF patients, had their DNA typed using sequence-specific primer (SSP) technique for the presence of 16 KIR gene and pseudogene loci, and compared them to the general Lebanese population. The AA1 genotype was the most frequent in both the FMF and control groups. Six new KIR profiles were identified. The FMF group showed a higher prevalence of KIR 3DP1*003 (p<0.05) and an increase in the BB genotype compared with controls. The results lead to an interesting future research question of whether or not KIR genotype is involved in the predisposition to or pathogenesis of FMF. This is the first report that describes the KIR genotypic profile in this important clinical disease.

Genotypic profiles of the Natural killer cell Immunoglobulin-like Receptors (KIR) have been reported to vary among different ethnic groups and this study represents a comparative report on its distribution between two Arabic populations in the Middle East: Lebanese and Palestinians. Our compared population samples included 120 unrelated healthy Lebanese (as per Mahfouz et al.) and a Palestinian population of 105 individuals (as per Norman et al.). All had their DNA typed using Sequence Specific Primer (SSP) technique for the presence of the different KIR loci. Similar to most published data, we observed that the two framework genes 2DL4 and 3DL2 are present in 100% of individuals from both communities, while 2DL2, 2DL3, 2DS1, 2DS2, 2DS3, 2DS5, 3DL1, and 3DS1 were very similar in frequency. However, significant differences were noted in the frequencies of 2DL1 and 2DS4. This report is comparing KIR genotyping distribution in two Arab populations that sheds additional light on the importance of this gene in delineating a possible geographic genetic demarcation among different ethnicities or even different communities among the same or close ethnic groups.