The historiography of protest in late Mamluk and early Ottoman Egypt and Syria

History in its various forms - chronicles, biographies and biographical dictionaries - was a favourite genre in late medieval Egypt and Syria. One of the salient features of these histories is their breadth of perspective. Matters related to community and urban life including market prices, fires, murders, epidemics, floods and social relations were considered worthy of record. The writers were profoundly interested in the events of their times rather than in classical Islamic history. In the absence of archives, these histories remain our widest windows on medieval Egypt and Syria

Prevalence and Health Adverse Effects of Khat Chewing Among College Students in Jazan Region, Saudi Arabia

Khat chewing is a social habit which has stimulatory action due to its cathinone content, but its adverse effects on health are a source of growing concern. The aim of our study is to evaluate the prevalence and health adverse effects of khat chewing among students in Jazan region in the Kingdom of Saudi Arabia (KSA). The study sample included 195 students from Applied Medical Science College, who were randomly selected and were asked through questionnaire and with a signed consent. About 5 ml of venous blood was collected in plain vacutainer tubes from 38 khat chewers and 20 non khat chewers as normal control. Serum was used to determine alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and direct bilirubin, total protein, urea, creatinine, uric acid, and albumin. The sample consisted of 134 males and 61 females, with age range 19-27 years, and their mean age was 21.1 year. 40% of students were from urban area, and 81.5% of them from Jazan region. Out of 195 students, only 38 (19.5%) were found to chew khat. Biochemical results revealed highly significant differences among chewers in ALT, ALP, uric acid, and urea (p<0.005) compared to nonchewers group. There is also a significant difference in the total protein level (<0.05), while no significant differences were noticed in other biochemical traits analyzed. We concluded that the prevalence of khat chewing among students is fairly high (19.5 %), and that adverse effects of khat chewing on health are very clear, so all efforts should be contributed to solve this problem by increasing awareness of all members of the society to khat chewing risk

One-stage lingual augmented urethroplasty in repair of distal penile hypospadias

AbstractObjectivesTo evaluate the outcome of augmentation of shallow urethral plate by lingual graft in repair of distal penile hypospadias.Patients and methodsBetween June 2008 and May 2011, the procedure was performed on 23 patients with mean age 2.3 years (range 1–3). All patients had distal penile hypospadias; 11 sub coronal and 12 coronal. The urethral plate was less than 8mm in all patients and 3 of them had history of previous hypospadias surgery. All procedures were carried out under general anesthesia using 4× magnifying loupe. After penile degloving and dorsal incision of the urethral plate, the lingual graft was harvested and sutured to the edges of the incised urethral plate from the hypospadias opening to the tip of the penis. The neourethra was closed and an intervening flap was fixed over the neourethra as a barrier against fistula formation.ResultsSuccess rate was 87% as 20/23 patients were cured without any permanent complication throughout the follow up period. None of patients suffered meatal stenosis or required regular urethral dilatation. Three patients developed urethrocutaneous fistula, of which two closed spontaneously and one required surgical repair 6 months later. Two patients had failed procedures and delayed re-intervention was performed due to complete loss of the graft in one of them and repair disruption following infection in the other. Two patients had post-operative pain in the graft harvesting site which disappeared within days.ConclusionThe one-stage lingual augmented urethral plate urethroplasty offers promising outcomes for repair of distal penile hypospadias with narrow urethral plate

In-depth characterization of neuroradiological findings in a large sample of individuals with autism spectrum disorder and controls

Background: Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions associated with quantitative differences in cortical and subcortical brain morphometry. Qualitative assessment of brain morphology provides complementary information on the possible underlying neurobiology. Studies of neuroradiological findings in ASD have rendered mixed results, and await robust replication in a sizable and independent sample. Methods: We systematically and comprehensively assessed neuroradiological findings in a large cohort of participants with ASD and age-matched controls (total N = 620, 348 ASD and 272 controls), including 70 participants with intellectual disability (47 ASD, 23 controls). We developed a comprehensive scoring system, augmented by standardized biometric measures. Results: There was a higher incidence of neuroradiological findings in individuals with ASD (89.4 %) compared to controls (83.8 %, p = .042). Certain findings were also more common in ASD, in particular opercular abnormalities (OR 1.9, 95 % CI 1.3–3.6) and mega cisterna magna (OR 2.4, 95 % CI 1.4–4.0) reached significance when using FDR, whereas increases in macrocephaly (OR 2.0, 95 % CI 1.2–3.2), cranial deformities (OR 2.4, 95 % CI: 1.0–5.8), calvarian / dural thickening (OR 1.5, 95 % CI 1.0–2.3), ventriculomegaly (OR 3.4, 95 % CI 1.3–9.2), and hypoplasia of the corpus callosum (OR 2.7, 95 % CI 1.1–6.3) did not survive this correction. Furthermore, neuroradiological findings were more likely to occur in isolation in controls, whereas they clustered more frequently in ASD. The incidence of neuroradiological findings was higher in individuals with mild intellectual disability (95.7 %), irrespective of ASD diagnosis. Conclusion: There was a subtly higher prevalence of neuroradiological findings in ASD, which did not appear to be specific to the condition. Individual findings or clusters of findings may point towards the neurodevelopmental mechanisms involved in individual cases. As such, clinical MRI assessments may be useful to guide further etiopathological (genetic) investigations, and are potentially valuable to fundamental ASD research

Restoration of TGF-β signalling reduces tumorigenicity in human lung cancer cells

Members of the transforming growth factor-β (TGF-β) family regulate a wide range of biological processes including cell proliferation, migration, differentiation, apoptosis, and extracellular matrix deposition. Resistance to TGF-β-mediated tumour suppressor function in human lung cancer may occur through the loss of type II receptor (TβRII) expression. In this study, we investigated the expression pattern of TβRII in human lung cancer tissues by RT–PCR and Western blot analyses. We observed downregulation of TβRII in 30 out of 46 NSCLC samples (65%) by semiquantitative RT–PCR. Western blot analyses with tumour lysates showed reduced expression of TβRII in 77% cases. We also determined the effect of TβRII expression in lung adenocarcinoma cell line (VMRC-LCD) that is not responsive to TGF-β due to lack of TβRII expression. Stable expression of TβRII in these cells restored TGF-β-mediated effects including Smad2/3 and Smad4 complex formation, TGF-β-responsive reporter gene activation, inhibition of cell proliferation and increased apoptosis. Clones expressing TβRII showed reduced colony formation in soft-agarose assay and significantly reduced tumorigenicity in athymic nude mice. Therefore, these results suggest that reestablishment of TGF-β signalling in TβRII null cells by stable expression of TβRII can reverse malignant behaviour of cells and loss of TβRII expression may be involved in lung tumour progression

Clinico-radiological features, molecular spectrum, and identification of prognostic factors in developmental and epileptic encephalopathy due to inosine triphosphate pyrophosphatase (ITPase) deficiency

Developmental and epileptic encephalopathy 35 (DEE 35) is a severe neurological condition caused by biallelic variants in ITPA, encoding inosine triphosphate pyrophosphatase, an essential enzyme in purine metabolism. We delineate the genotypic and phenotypic spectrum of DEE 35, analyzing possible predictors for adverse clinical outcomes. We investigated a cohort of 28 new patients and reviewed previously described cases, providing a comprehensive characterization of 40 subjects. Exome sequencing was performed to identify underlying ITPA pathogenic variants. Brain MRI (magnetic resonance imaging) scans were systematically analyzed to delineate the neuroradiological spectrum. Survival curves according to the Kaplan–Meier method and log-rank test were used to investigate outcome predictors in different subgroups of patients. We identified 18 distinct ITPA pathogenic variants, including 14 novel variants, and two deletions. All subjects showed profound developmental delay, microcephaly, and refractory epilepsy followed by neurodevelopmental regression. Brain MRI revision revealed a recurrent pattern of delayed myelination and restricted diffusion of early myelinating structures. Congenital microcephaly and cardiac involvement were statistically significant novel clinical predictors of adverse outcomes. We refined the molecular, clinical, and neuroradiological characterization of ITPase deficiency, and identified new clinical predictors which may have a potentially important impact on diagnosis, counseling, and follow-up of affected individuals

High-Content, High-Throughput Analysis of Cell Cycle Perturbations Induced by the HSP90 Inhibitor XL888

BACKGROUND: Many proteins that are dysregulated or mutated in cancer cells rely on the molecular chaperone HSP90 for their proper folding and activity, which has led to considerable interest in HSP90 as a cancer drug target. The diverse array of HSP90 client proteins encompasses oncogenic drivers, cell cycle components, and a variety of regulatory factors, so inhibition of HSP90 perturbs multiple cellular processes, including mitogenic signaling and cell cycle control. Although many reports have investigated HSP90 inhibition in the context of the cell cycle, no large-scale studies have examined potential correlations between cell genotype and the cell cycle phenotypes of HSP90 inhibition. METHODOLOGY/PRINCIPAL FINDINGS: To address this question, we developed a novel high-content, high-throughput cell cycle assay and profiled the effects of two distinct small molecule HSP90 inhibitors (XL888 and 17-AAG [17-allylamino-17-demethoxygeldanamycin]) in a large, genetically diverse panel of cancer cell lines. The cell cycle phenotypes of both inhibitors were strikingly similar and fell into three classes: accumulation in M-phase, G2-phase, or G1-phase. Accumulation in M-phase was the most prominent phenotype and notably, was also correlated with TP53 mutant status. We additionally observed unexpected complexity in the response of the cell cycle-associated client PLK1 to HSP90 inhibition, and we suggest that inhibitor-induced PLK1 depletion may contribute to the striking metaphase arrest phenotype seen in many of the M-arrested cell lines. CONCLUSIONS/SIGNIFICANCE: Our analysis of the cell cycle phenotypes induced by HSP90 inhibition in 25 cancer cell lines revealed that the phenotypic response was highly dependent on cellular genotype as well as on the concentration of HSP90 inhibitor and the time of treatment. M-phase arrest correlated with the presence of TP53 mutations, while G2 or G1 arrest was more commonly seen in cells bearing wt TP53. We draw upon previous literature to suggest an integrated model that accounts for these varying observations

Phenotypic continuum of NFU1-related disorders.

Bi-allelic variants in Iron-Sulfur Cluster Scaffold (NFU1) have previously been associated with multiple mitochondrial dysfunctions syndrome 1 (MMDS1) characterized by early-onset rapidly fatal leukoencephalopathy. We report 19 affected individuals from 10 independent families with ultra-rare bi-allelic NFU1 missense variants associated with a spectrum of early-onset pure to complex hereditary spastic paraplegia (HSP) phenotype with a longer survival (16/19) on one end and neurodevelopmental delay with severe hypotonia (3/19) on the other. Reversible or irreversible neurological decompensation after a febrile illness was common in the cohort, and there were invariable white matter abnormalities on neuroimaging. The study suggests that MMDS1 and HSP could be the two ends of the NFU1-related phenotypic continuum