The Genetics of Amyotrophic Lateral Sclerosis: Current Insights

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that results in loss of the upper and lower motor neurons from motor cortex, brainstem and spinal cord. Whilst the majority of cases are sporadic, around 10% show familial inheritance. ALS is usually inherited in an autosomal dominant manner, though autosomal recessive and X-linked inheritance do occur. To date, 24 of the genes at 26 loci have been identified; these include loci linked to ALS as well as to FTD-ALS, where family pedigrees contain individuals with frontotemporal dementia with/without ALS. The most commonly established genetic causes of FALS to date are the presence of a hexanucleotide repeat expansion in the C9ORF72 gene (39.3% FALS) and mutation of SOD1, TARDBP and FUS, with frequencies of 12-23.5%, 5% and 4.1% respectively. However, with the increasing use of next generation sequencing of small family pedigrees, this has led to an increasing number of genes associated with ALS. This review provides a comprehensive review on the genetics of ALS and an update of the pathogenic mechanisms associated with these genes. Commonly implicated pathways have been established, including RNA processing, the protein degradation pathways of autophagy and ubiquitin-proteasome-system as well as protein trafficking and cytoskeletal function. Elucidating the role genetics plays in both FALS and SALS is essential for understanding the subsequent cellular dysregulation that leads to motor neuron loss, in order to develop future effective therapeutic strategies

Application of a new grading scale for tear ferning in non-dry eye and dry eye subjects

The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.clae.2014.09.007 © 2014. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Purpose: To apply the Masmali tear ferning (TF) grading scale on non-dry eye (NDE) and dry eye (DE) subjects to test the validity of the grading scale in practice, and to describe the grading scale range for NDE and DE. Method: Forty NDE subjects (20 males, 20 females) and 40 DE subjects (23 males, 17 females) ranging in age from 19 to 53 years (mean ± SD: 25.3 ± 5.5) with no other ocular disease, no contact lens wear, and not pregnant or breastfeeding were recruited. McMonnies scores were used for subject grouping. Phenol red thread (PRT) and slit-lamp test were used. A tear sample was collected from right eye, which was then dried to produce a ferning pattern, that was observed using a digital microscope, and graded. Results: Mean McMonnies, PRT and TF grade in NDE subjects were 7.1 ± 3.8, 27.4 ± 4.3 mm and 0.78 ± 0.40, respectively. Median McMonnies, PRT and TF grade in DE subjects were 16.5 ± 3.0, 9.0 ± 2.0 mm and 2.3 ± 1.48, respectively. In NDE subjects, grades 0.0–1.8 were observed (82.5% Grade 0.0–1.00). Grades 2.0–4.0 were observed in DE subjects (72.5% Grades 2.0–3.0). For all subjects, there were large correlations between TF grade and PRT (r = −0.79), PRT and McMonnies (r = −0.60), and TF and McMonnies (r = 0.73). Conclusions: The Masmali TF grading scale showed good validity in describing the TF patterns. Grades ≥2 can be classified as abnormal patterns. The TF test has the potential to be used in the clinic

Variation in gas chromatography (GC) analysis in setting up laboratory protocols for waste to energy novel fixed bed reactor setups

Gas Chromatography coupled with Mass Spectrometry (GC/MS) has been applied in various analytical chemistry works. However, to fine tune a system that can serve the purposes of pyrolysis oil identification has proven to be a laborious effort, especially when considering the fact that no standard protocol exists for such analysis. In addition, obtained products were yielded from a newly commissioned unit with a unique and novel design. In this study, a US patent office claimed reactor [SULTAN-1, Pyrolysis Reactor System for the Conversion and Analysis of Organic Solid Waste, Patent application number: 15,487,351] that degrades polyolefinc virgin and waste materials to obtain petroleum refinery and petrochemical feedstock, has been commissioned. The reactor produces three distinct physical states of matter products accumulated as testing specimens, i.e. solids, gaseous and oil. The samples analysed in this work were of the gas and oil produced by pyrolysis of end of life tyre (ELTs) shavings that required to have a special recipe to work with in the laboratory. Various MS cords were utilised and experimental setups to fine tune the process, and special emphasis was given on the gas samples variation in this communication. To reach the desired analysis results with high repeatability, a plethora of experiences of lab personnel and laboratory-based experimental work was accumulated. Laboratory protocols were also setup for this work. These will be detailed along the process execution which yielded a standard laboratory best practice analytical method as part of the State of Kuwait newly initiated Government Initiative project

Durability of multi layered plasma and HVOF coatings

The aim of this research is to investigate the effect of variable compositional coating layers on their mechanical and chemical behaviour under certain environments typically experienced in the Oil and Gas Industry. The research centers on using thermal spray coating techniques such as the HVOF and plasma spray equipment. The coating was applied onto selected carbon steel substrates (API-5L, Schedule-40, Grade-B) to simulate the material application used in oil and gas components that subject to corrosion and corrosion-erosion phenomena. The coating was deposited using three layers of coatings with various combinations of sprayed powders to create graded multi-layered coating. WC-12Co powders with two different powder structures (micro-sized powders and nano-sized agglomerated into micro-sized powders – nano-structured) were mixed at different ratios with AMDRY (9954 and 995M) powders to enhance the mechanical behaviour, wear, and corrosion protection (Hardness, corrosion, erosion-corrosion) of the coatings. The surface morphology and the elemental composition of the coatings were examined using SEM and EDS techniques. The results indicated that coating deposited by the HVOF (60% Micro WC-12Co and 40% Micro AMDRY 9954) was the most effective coating system in preventing corrosion. If the erosion is the dominant concern, then replacing the Microsized WC-12Co powder with the Nanosized WC-12Co powder is effective for protecting materials from wear caused by erosion-corrosion. The addition of the AMDRY powder to the original WC-Co powders helped to lower the overall coating porosity, enhanced the corrosion protection, and improved the overall erosion–corrosion performance, which addresses issues currently faced in the Oil/Gas industry. A Design of Experiment (DOE) technique may be used to optimize the powders blending ratios to give better results in future work

Task Based English Language Teaching in Saudi Intermediate Schools

This study investigates the effectiveness and appropriateness of a constructivist instructional practice for EFL. It strives to determine whether adopting Task-Based Language Teaching (TBLT) is a more effective means to increase students’ reading comprehension when compared to that of the traditional teaching method. It also attempts to gain understandings that accompany TBLT implementation through constant comparison and contrast them with those that accompany the traditional teaching method. The mixed-method study covers quasi-experimental approach that uses one pretest and several posttests to collect quantitative data, as well as classroom observation and researcher log to collect qualitative data. The independent variable is the use of TBLT and the dependent variable is the students’ reading comprehension achievement scores. A Two-Factor Split Plot analysis with pretest as the covariate is used for analyzing the quantitative data. The analysis of qualitative data includes synthesis, rich, and detailed descriptions for classroom observation and grounded theory for researcher log data. Keywords: Task Based Language Teaching, Constructivist Instructional Practice

In-Vitro Comparison of Aerosol Drug Delivery in Pediatrics Using Pressurized Metered Dose Inhaler, Jet Nebulizer, and Vibrating Mesh Nebulizers

Background: Aerosol therapy has been established as an efficient form of drug delivery to pediatric and adult patients with respiratory diseases; however, aerosol delivery to the pediatric population is quite challenging. While some studies compare jet nebulizer (JN), vibrating mesh nebulizer (VMN), or JN and pMDI, there is no study comparing these three devices in pediatric and young children. The aim of this study quantifies aerosol deposition using JN, VMN, and pMDI/VHC in a simulated pediatric with active and passive breathing patterns. Methods: Each aerosol generator was placed between manual resuscitator bag (Ambu SPUR II Disposable Resuscitator, Ambu Inc, Glen Burnie, MD) and infant facemask (Mercury Medical, Cleanwater, FL), which was held tightly against the SAINT model. Breathing parameters used in this study were Vt of 100 mL, RR of 30 breaths/min, and I:E ratio of 1: 1.4. Active and passive breathing patterns were used in this study with aerosol device; active breathing pattern was created using a ventilator (Esprit Ventilator, Respironics/Philips Healthcare, Murrysville, PA) connected to a dual chamber test lung (Michigan Instruments, Grand Rapids, MI), which was attached to an absolute filter (Respirgard II, Vital Signs Colorado Inc, Englewood, CO), to collect aerosolized drug, connected to the SAINT model. Pediatric resuscitator bag was run at 10 L/min of oxygen and attached to aerosol generator with facemask. In passive breathing pattern, SAINT model was attached to test lung and ventilated using the resuscitator bag with the same breathing parameters. Each aerosol device was tested three times (n=3) with each breathing patterns. Drug was eluted from the filter and analyzed using spectrophotometry. The amount of drug deposited on the filter was quantified and expressed as a percentage of the total drug dose. To measure the differences in the inhaled drug mass between JN, VMN, and pMDI/VHC in active or passive breathing, one-way analysis of variance (one-way ANOVA) was performed. To quantify the difference in aerosol depositions between the two breathing patterns, independent t-test was performed. A p \u3c 0.05 was considered to be statistically significant. Results: Although the amount of aerosol deposition with the JN was the same in passive and active breathing without any significant difference, the VMN was more efficient in active breathing than the JN (p = 0.157 and p = 0.729, respectively). pMDI/VHC had the greatest deposition in the simulated spontaneous breathing (p=0.013) Conclusion: Aerosol treatment may be administered to young children using JN, VMN, or pMDI/VHC combined with resuscitator bag. Using pMDI/VHC with resuscitator bag is the best choice to deliver albuterol in spontaneously breathing children. Further studies are needed to determine the effectiveness of these aerosol generators with different type of resuscitator bag and different breathing parameters

Ki67 expression in invasive breast cancer: the use of tissue microarrays compared with whole tissue sections.

BACKGROUND: Although the prognostic value of Ki67 in breast cancer is well documented, using optimal cut-points for patient stratification, reproducibility of the scoring and interpretation of the results remains a matter of debate particularly when using tissue microarrays (TMAs). This study aims to assess Ki67 expression assessed on TMAs and their matched whole tissue sections (WTS). Moreover, whether the cut-off used for WTS is reproducible on TMA in BC molecular classes and the association between Ki67 expression cut-off, assessed on TMAs and WTS, and clinicopathological parameters and patient outcome were tested. METHOD: A large series (n = 707) of primary invasive breast tumours were immunostained for Ki67 using both TMA and WTS and assessed as percentage staining and correlated with each other, clinicopathological parameters and patient outcome. In addition, MKI67 mRNA expression was correlated with Ki67 protein levels on WTS and TMAs in a subset of cases included in the METABRIC study. RESULTS: There was moderate concordance in Ki67 expression between WTS and TMA when analysed as a continuous variable (Intraclass correlation coefficient = 0.61) and low concordance when dichotomised (kappa value = 0.3). TMA showed low levels of Ki67 with mean percentage of expression of 35 and 22% on WTS and TMA, respectively. MKI67 mRNA expression was significantly correlated with protein expression determined on WTS (Spearman Correlation, r = 0.52) and to a lesser extent on TMA (r = 0.34) (p < 0.001). Regarding prediction of patient outcome, statistically significant differences were detected upon stratification of patients with tumours expressing Ki67 at 10, 15, 20, 25 or 30% in TMA. Using TMA, ≥20% Ki67 provided the best prognostic cut-off particularly in triple-negative and HER2-positive classes. CONCLUSION: Ki67 expression in breast cancer can be evaluated using TMA although different cut-points are required to emulate results from WTS. A cut-off of ≥20% for Ki67 expression in BC provides the best prognostic correlations when TMAs are used

Lack of association between polymorphism rs540782 and primary open angle glaucoma in Saudi patients.

Background To investigate whether polymorphism rs540782 on chromsome 1, in close proximity to the Zona Pellucida Glycoprotein 4 (ZP4) gene, is a risk factor for primary open angle glaucoma (POAG). Method The study genotyped 92 unrelated POAG cases and 95 control subjects from Saudi Arabia using Taq-Man® assay. Results The genotype frequency distribution did not deviate significantly from the Hardy-Weinberg equilibrium (p > 0.05). Overall, both the genotype and allele frequencies were not significantly different between cases and controls. The minor ‘C’ allele frequency was 49.4%, which was comparable to the Japanese population and higher than the Indian and Afro-Caribbean populations. Similarly, no significant association was found between genotypes and systemic diseases and health awareness/behavior domain variables. Importantly, glaucoma specific indices, such as intraocular pressure, cup/disc ratio and number of anti-glaucoma medication, also showed no statistically significant effect of genotypes within POAG cases. Conclusion Polymorphism rs540782 is not a risk factor for POAG in the Saudi cohort

Molecular epidemiology and genotype distribution of Human Papillomavirus (HPV) among Arab women in the state of Qatar

Background: Human Papilloma Virus (HPV) infection is the major cause of cervical cancer worldwide. With limited data available on HPV prevalence in the Arab countries, this study aimed to identify the prevalence and genotypic distribution of HPV in the State of Qatar. Methods: 3008 cervical samples, exclusively of women with Arabic origin residing in Qatar were collected from the Women’s Hospital and Primary Health Care Corporation in Doha, State of Qatar. HPV DNA detection was done using GP5+/6+ primers based real time-polymerase chain reaction (RT-PCR) assay followed by the usage of HPV type specific primers based RT- PCR reactions and Sanger sequencing for genotype identification. Results: Similar prevalence rates of HPV infection was identified in both Qatari and non-Qatari women at 6.2% and 5.9% respectively. HPV prevalence rate of 5.8% and 18.4% was identified in women with normal cytology and in women with abnormal cytology respectively. HPV 81, 11 and 16, in decreasing order were the most commonly identified genotypes. HPV 81 was the most frequent low-risk genotype among women with both normal (74.0%) and abnormal (33.3%) cytology. HPV 16 (4.6%) was identified as the predominant high-risk HPV genotype among women with normal cytology and HPV 16, HPV 18, and HPV 56 (22.2% each) were the most common identified high-risk genotypes in women with abnormal cytology Conclusions: The overall HPV prevalence in Arab women in Qatar was identified as 6.1% with an increased HPV prevalence seen in women with abnormal cytology results and no significant trends seen with age. In contrast to Western countries, we report a varied genotypic profile of HPV with a high prevalence of low-risk HPV genotype 81 among the Arab women residing in Qatar.Weill Cornell Medical College in Qatar; and by a grant from the Qatar National Research Fund (NPRP- 09-344-3-082)

Study On the Parasites of Falcons in the United Arab Emirates

Sakers Falco cherrug, Gyrfalcons Falco rusticolus, Peregrines Falco peregrilllls, in addition to Hybrids (saker X gyrfalcon, or gyrfalcon X peregrine), were found to be the most popular species of falcons in United Arab Emirates (UAE). The importance of falcons and falconry in Arabia was highlighted with a brief history of falconry in Arabia. The study focused on the prevalence of intestinal parasites (coccidia, helminthes and nematodes) and blood parasites (Haemoproteus sp. and Leucocytozoon sp.) as well as ecto-parasites (Ticks and Mites) of these falcons, with discussion on the possible sources of infection in view of the epizootiology of these parasites. 100 falcons, 89 females and 11 males, were studied at random. Of these 100 falcons, 50 falcons were considered as resident falcons having spent a period of 1-4 years in the UAE, the rest (50 falcons) with less than 1-year residence were considered imported falcons . The falcons were identified, thin blood smears were taken stained with Giemsa, examined for blood parasites and positive smears were identified. Fresh feces were collected for macroscopic examination to recognize adult worms, segments of tapeworms or fly larvae, then fecal materials were prepared (direct and floatation methods) for microscopic examination to detect protozoan cyst and helminthes eggs. Three techniques: feathers inspection, insecticide spray, and shaking the body in full sun light, were used for collecting ecto-parasites. The results were presented in term of numbers and percentages of non-infected and infected imported and resident falcons in relation to species and sex. 52% (26/50) of imported falcons showed parasitic infections, while 38% (19/50) of resident falcons were found to be infected. The results were compared with those of other researchers. Emphasis was also laid on the pathological aspects of parasitic infection in falcons. Recommendations that would lead to significant decrease in the infection rates in falcons in the UAE were made