Brain abscess following rituximab infusion in a patient with pemphigus vulgaris.

BackgroundImmunocompromised patients are at increased risk for developing meningitis or, rarely, brain abscess with opportunistic organisms like Listeria monocytogenes.Case reportA 52 year-old Saudi Arabian woman who was diagnosed with pemphigus vulgaris and diabetes and had been on prednisolone and azathioprine for about 4 years. She presented with headache, low-grade fever, and left-sided weakness 2 weeks after receiving the second dose of rituximab infusion. Magnetic resonance imaging revealed an enhanced space-occupying lesion with multiple small cyst-like structures and vasogenic edema in the right temporoparietal area. Her blood culture was positive for Listeria monocytogenes, and a brain biopsy showed necrotic tissues with pus and inflammatory cells. She recovered after a 6-week course of antibiotics with ampicillin and gentamycin.ConclusionsBrain abscess due to Listeria monocytogenes is a risk that should be considered when adding rituximab to the regimen of a patient who is already Immunocompromised

The Category 'D' Reconsidered

This study deals with the categorial status of a set of words known as 'determiners' and the features encoded in them. We argue, following a suggestion in Chomsky, 1975, that 'Optimality' conditions on grammar require grammatical categories to be 'primitive' in the sense that they must be unanalysable into further entities. The status of many words classified as determiners does not conform with this suggestion. The category 'D' is therefore a non-standard grammatical category. We have provided mathematical, morphological and syntactic arguments and facts drawn from a number of languages including Arabic, English, French, German, Hebrew, Italian, ...etc. showing that the category 'D' is not a 'primitive' category and therefore should be suspended and replaced by its 'primitive5 components. We have shown that 'genuine' determiners are morphologically complex where each element encodes a functional feature, such as 'person9, 'number9, 'gender9, 'proximate', 'definite', ...etc. These features, we claim, are functional categories. Many words classified as belonging to the category 'd' are in fact nouns or adjectives. Adopting an articulated theory of 'D' in which functional features are taken as functional categories is not only theoretically motivated but also has implications for language learn ability

A novel homozygous TPM1 mutation in familial pediatric hypertrophic cardiomyopathy and in silico screening of potential targeting drugs.

Familial hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease. While sarcomeric gene mutations explain many HCM cases, the genetic basis of about half of HCM cases remains elusive. Here we aimed to identify the gene causing HCM in a non-consanguineous Saudi Arabian family with affected family members and a history of sudden death. The impact of the identified mutation on protein structure and potential drug targets were evaluated in silico. Triplets (two HCM subjects and one patent ductus arteriosus (PDA) case) and unaffected parents were screened by targeted next-generation sequencing (NGS) for 181 candidate cardiomyopathy genes. In silico structural and functional analyses, including protein modeling, structure prediction, drug screening, drug binding, and dynamic simulations were performed to explore the potential pathogenicity of the variant and to identify candidate drugs. A homozygous missense mutation in exon 1 of TMP1 (assembly GRCh37-chr15: 63340781; G>A) was identified in the triplets [two HCM and one patent ductus arteriosus (PDA)] that substituted glycine for arginine at codon 3 (p.Gly3Arg). The parents were heterozygous for the variant. The mutation was predicted to cause a significant and deleterious change in the TPM1 protein structure that slightly affected drug binding, stability, and conformation. In addition, we identified several putative TPM1-targeting drugs through structure-based in silico screening. TPM1 mutations are a common cause of HCM and other congenital heart defects. To date, TPM1 has not been associated with isolated PDA; to our knowledge, this is the first report of the homozygous missense variation p.Gly3Arg in TPM1 associated with familial autosomal recessive pediatric HCM and PDA. The identified candidate TPM1 inhibitors warrant further prospective investigation.This research was supported by the Strategic Technologies Programs of the National Plan for Science, Technology and Innovation (MAARIFAH), Kingdom of Saudi Arabia. Project No: 12-MED3174-05, through the Science and Technology Unit (STU), Taibah University, Al Madinah Al Munawwarah, Kingdom of Saudi Arabia

29. No association between MTHFR C677T polymorphism and congenital heart disease in Saudi Arabian population

Congenital heart diseases (CHD) are the most common birth defects in the world. It is a major cause of childhood mortality and morbidity worldwide with about 7 per 1000 live birth. Studies suggest that Methylenetetrahydrofolate reductase (MTHFR) polymorphism C667T has been associated with congenital malformation; this common missense mutation in the MTHFR gene may reduce enzymatic action, and may be involved in the etiology of congenital heart defects (CHD), but the evidence remains inconclusive. The aim of this study is to determine whether this association exists in the Saudi Arabian population.MethodDNA sequencing was used to detect genotype MTHFR C677T in 75 CHD patients and 100 ethnically similar controls. The type of cardiac defect was diagnosed by cardiovascular specialist and confirmed by echocardiographic.ResultsThe distribution of the MTHFR 677C >T SNP genotypes and alleles in both CHD and control groups were 70.0% CC, 26.0% CT, 4.0% TT in cases and 70.8% CC, 25.4% CT, 3.8% TT in controls. The T allele frequency was 17.0% in cases and 16.5% in controls. The difference between genotypes and alleles was not statistically significant between controls and the CHD groups.ConclusionWe did not find sufficient evidence for an association between MTHFR C677T genotype and congenital heart disease in Saudi Arabian population. We agree that the sample size is a limitation to our above conclusions

Human-Induced Geo-Hazards in the Kingdom of Saudi Arabia: Distribution, Investigation, Causes and Impacts

Different types of geological hazards are induced by human activities in the Kingdom of Saudi Arabia (KSA). These geological hazards include land subsidence and earth fissures, sinkholes, expansive soils, and flash floods. A wide variety of recent geological hazards have been reported in several areas, causing significant human and property losses. Human activities, most notably groundwater extraction, infrastructure development, and agricultural activities, have induced unstable conditions. This chapter provides an overview of the human-induced geological hazard in the KSA, mainly earth fissures and sinkhole, which represent a scarcely explored topic. This work identifies the main types of human-induced geological-hazard formations, distribution, causes, and impacts, illustrated through several case studies in the KSA

Association between Paraoxonases Gene Expression and Oxidative Stress in Hepatotoxicity Induced by CCl 4

Objectives. The purpose of the study is to evaluate the hepatoprotective effect of rutin in carbon tetrachloride- (CCl4-) induced liver injuries in rat model. Methods. Forty male Wistar albino rats were divided into four groups. Group I was the control group and received dimethyl sulphoxide (DMSO) and olive oil. Group II received rutin. Groups III was treated with CCl4. Group IV was administered rutin after 48 h of CCl4 treatment. Liver enzymes level, lipid profile, lipid peroxidation, and hydrogen peroxide were measured. The genes expression levels were monitored by real time RT-PCR and western blot techniques. Results. CCl4 group showed significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), thiobarbituric acid reactive substances (TBAR), hydrogen peroxide (H2O2), and lipid profile and a significant decrease in glutathione peroxidase (GPx), glutathione S transferase (GST), catalase (CAT), paraoxonase-1 (PON-1), paraoxonase-3 (PON-3), peroxisome proliferator activated receptor delta (PPAR-δ), and ATP-binding cassette transporter 1 (ABAC1) genes expression levels. Interestingly, rutin supplementation completely reversed the biochemical and gene expression levels induced by CCl4 to control values. Conclusion. CCl4 administration causes aberration of genes expression levels in oxidative stress pathway resulting in DNA damage and hepatotoxicity. Rutin causes hepatoprotective effect through enhancing the antioxidant genes

Sequence analysis of the VSX1 and SOD1 genes in families with Keratoconus and a review of the literature

AbstractObjectiveKeratoconus (KC) is a non-inflammatory disorder of the cornea in which the cornea becomes thin and conical, inducing myopia and irregular astigmatism and resulting in mild to marked impairment of vision. The present study was designed to screen two candidate KC genes to identify pathogenic sequence variants responsible for KC in Saudi families.MethodsPeripheral blood samples from members of five Saudi families with KC from the Northern region were collected. Genomic DNA was isolated, and bidirectional sequencing was performed of all coding exons of VSX1 and SOD1 genes using Sanger sequencing.ResultsAll five of the KC families showed a pattern of autosomal recessive inheritance. Phenotyping of these families was performed by a senior ophthalmologist. Sequence analysis of the VSX1 and SOD1 genes failed to reveal any pathogenic sequence variant that could account for KC in the affected individuals.ConclusionOur failure to detect sequence variants in two of the known KC associated genes triggers an interest in other known KC candidate genes, including miR-184, DOCK9, IL1RN and SLC4A11. Future genotyping with dense SNP arrays followed by exome sequencing in these families will be a useful approach to identify the gene(s) underlying KC in this Saudi cohort, which may be different from those reported elsewhere

A Flood Risk Management Program of Wadi Baysh Dam on the Downstream Area: An Integration of Hydrologic and Hydraulic Models, Jizan Region, KSA

For public safety, especially for people who dwell in the valley that is located downstream of a dam site, as well as the protection of economic and environmental resources, risk management programs are urgently required all over the world. Despite the high safety standards of dams because of improved engineering and excellent construction in recent times, a zero-risk guarantee is not possible, and accidents can happen, triggered by natural hazards, human actions, or just because the dam is aging. In addition to that is the impact of potential climate change, which may not have been taken into account in the original design. A flood risk management program, which is essential for protecting downstream dam areas, is required. Part of this program is to prepare an inundation map to simulate the impact of dam failure on the downstream areas. The Baysh dam has crucial importance both to protect the downstream areas against flooding, to provide drinking water to cities in the surrounding areas, and to use the excess water for irrigation of the agricultural areas located downstream of the dam. Recently, the Kingdom of Saudi Arabia (KSA) was affected by extraordinary rainstorm events causing many problems in many different areas. One of these events happened along the basin of the Baysh dam, which raised the alarm to the decision makers and to the public to take suitable action before dam failure occurs. The current study deals with a flood risk analysis of Wadi Baysh using an integration of hydrologic and hydraulic models. A detailed field investigation of the dam site and the downstream areas down to the Red Sea coast has been undertaken. Three scenarios were applied to check the dam and the reservoir functionality; the first scenario at 100-and 200-year return period rainfall events, the second scenario according to the Probable Maximum Precipitation (PMP), and the third scenario if the dam fails. Our findings indicated that the Baysh dam and reservoir at 100-and 200-year rainfall events are adequate, however, at the PMP the water will spill out from the spillway at ~8900 m3/s causing flooding to the downstream areas; thus, a well-designed channel along the downstream wadi portion up to the Red Sea coast is required. However, at dam failure, the inundation model indicated that a vast area of the section downstream of the dam will be utterly devastated, causing a significant loss of lives and destruction of urban areas and agricultural lands. Eventually, an effective warning system and flood hazard management system are imperative

The effect of nanodiamonds on candida albicans adhesion and surface characteristics of PMMA denture base material : an in vitro study

Candida albicans is the main causative pathogen of denture stomatitis, which affects many complete denture patients. Objective: To evaluate the effect of different concentrations of nanodiamonds (NDs) added to polymethyl methacrylate (PMMA) denture base material on Candida albicans adhesion as well as on surface roughness and contact angle. Methodology: Acrylic resin specimens sized 10×10×3 mm3 were prepared and divided into four groups (n=30) according to ND concentration (0%, 0.5%, 1%, 1.5% by wt). Surface roughness was measured with a profilometer, and the contact angle with a goniometer. The effect of NDs on Candida albicans adhesion was evaluated using two methods: 1) slide count and 2) direct culture test. Analysis of variance (ANOVA) and Tukey's post hoc test were used in the statistical analyses. Results: Addition of NDs decreased the Candida albicans count significantly more than in the control group (p<0.05), with a lowest of 1% NDs. Addition of NDs also significantly decreased the surface roughness (p<0.05), but the contact angle remained the same. Incorporation of NDs into the PMMA denture base material effectively reduced Candida albicans adhesion and decreased surface roughness. Conclusion: PMMA/NDs composites could be valuable in the prevention of denture stomatitis, which is considered one of the most common clinical problems among removable denture wearers

The role of nicotinamide in acne treatment

Safe and effective treatment options for acne vulgaris are needed to address side effects and increasing rates of antibiotic resistance from current treatments. Nicotinamide is a vitamin with potent antiâ inflammatory properties that could offer a potential treatment option. We aim to summarize the relevant literature on the role of nicotinamide in acne vulgaris and discuss the next steps necessary to move this approach into clinical practice. We searched PubMed for clinical studies using nicotinamide for treatment of acne vulgaris. We summarized the 10 studies that met our search criteria. Six of eight studies using topical nicotinamide led to a significant reduction in acne compared with the patient’s baseline or performed similarly to another standardâ ofâ care acne treatment. Both studies using an oral supplement containing nicotinamide resulted in a significant reduction in acne compared with baseline. No major adverse side effects were noted. Our review suggests that topical and oral nicotinamide has an unclear effect on acne vulgaris due to the limited nature of the available literature. Additional studies are needed comparing nicotinamide to other firstâ line acne treatments and evaluating the efficacy and side effect profile of nicotinamide over an extended period of time.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138875/1/dth12481_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138875/2/dth12481.pd