EFFECT OF OPENIINGS WITH OR WITHOUT STRENGHENING ON PUNCHING SHEAR STRENGTH FOR REINFORCED CONCRETE FLAT PLATES

Reinforced concrete slabs with openings are usually designed with help of traditional rules proposed by building codes. Such methods introduce limitations concerning size, location of openings and magnitude of applied loads. Furthermore, there are some traditional approaches to strengthen reinforced concrete slabs with openings which can be either cumbersome or expensive. This paper studies variable locations of an opening with respect to a central column in reinforced concrete flat plates, and presents a good approach to strengthen this opening by using steel plates. Nine reinforced concrete flat plates are cast with dimensions (length, width and thickness) equal to (850, 470 and 50) mm) using a single concrete mix with average compressive strength (fcu) equals 30 MPa. Each slab contains a square cross-section opening (side length =75 mm) and supported by a central square crosssection column (side length =75 mm). The variables of this study are: the type of opening (with or without strengthening) and the clear distance between the opening and the column which takes the values (0.0d, 2d, 4.5d and 7d), where d is the effective depth. The specimens are tested over a simply supported span at four edges.The test results show that, the ultimate load reaches the maximum value for slab without opening while this load reaches the minimum value for slab with a non-strengthening opening and lies in the pattern of the failure zone (where the clear distance between the column and the opening equals 4.5d). When a comparison is made between the test results ,it is concluded that ;strengthening the slab opening with steel plates causes increasing in the ultimate load by (19.44 ,19.51 ,35.13 and 13.46) % for the specimens (0.0d ,2d ,4.5d and 7d ) respectively

Finite Element Analysis of Reinforced Concrete T-Beams with Multiple Web Openings under Impact Loading

In this study, a three-dimensional finite element analysis using ANSYS 12.1 program had been employed to simulate simply supported reinforced concrete (RC) T-beams with multiple web circular openings subjected to an impact loading. Three design parameters were considered, including size, location and number of the web openings. Twelve models of simply supported RC T-beams were subjected to one point of transient (impact) loading at mid span. Beams were simulated and analysis results were obtained in terms of mid span deflection-time histories and compared with the results of the solid reference one. The maximum mid span deflection is an important index for evaluating damage levels of the RC beams subjected to impact loading. Three experimental T-beams were considered in this study for calibration of the program. All models had an identical cross-section and span similar to those of the experimental beams. The diameter of the openings of the experimental beams was 110 mm. Three other diameters were varied (50, 80 and 130) mm. The location of the face of the opening with respect to the location of impact loading was investigated (the face of the opening at distance varied 0d, 0.5d, 1d and 1.5d from the location of loading, where d is the effective depth) and the number of web openings was varied (2,4 and 6) openings. All modeled beams subjected to dropping mass of 24.5 kg with height of drop of 250 mm (as for the experimental beams). Results obtained from this study showed that the behavior of beams with circular openings of diameter equal to 22% the web depth has a small effect on the response of the RC T-beams. On the other hand, introducing circular openings with a diameter equal to 35% and 57% of the web depth (80 and 130 mm) increases the maximum mid span deflection by 23% and 43% respectively. Results also showed that, openings with a distance greater than or equal to 1.5 d from the location of impact loading have no effect on the deflection of the RC beams

The role of inflammation in subventricular zone cancer

The adult subventricular zone (SVZ) stem cell niche has proven vital for discovering neurodevelopmental mechanisms and holds great potential in medicine for neurodegenerative diseases. Yet the SVZ holds a dark side - it can become tumorigenic. Glioblastomas can arise from the SVZ via cancer stem cells (CSCs). Glioblastoma and other brain cancers often have dismal prognoses since they are resistant to treatment. In this review we argue that the SVZ is susceptible to cancer because it contains stem cells, migratory progenitors and unusual inflammation. Theoretically, SVZ stem cells can convert to CSCs more readily than can postmitotic neural cells. Additionally, the robust long-distance migration of SVZ progenitors can be subverted upon tumorigenesis to an infiltrative phenotype. There is evidence that the SVZ, even in health, exhibits chronic low-grade cellular and molecular inflammation. Its inflammatory response to brain injuries and disease differs from that of other brain regions. We hypothesize that the SVZ inflammatory environment can predispose cells to novel mutations and exacerbate cancer phenotypes. This can be studied in animal models in which human mutations related to cancer are knocked into the SVZ to induce tumorigenesis and the CSC immune interactions that precede full-blown cancer. Importantly inflammation can be pharmacologically modulated providing an avenue to brain cancer management and treatment. The SVZ is accessible by virtue of its location surrounding the lateral ventricles and CSCs in the SVZ can be targeted with a variety of pharmacotherapies. Thus, the SVZ can yield aggressive tumors but can be targeted via several strategies

Validation of plasma protein glycation and oxidation biomarkers for the diagnosis of autism

Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder in children. It is currently diagnosed by behaviour-based assessments made by observation and interview. In 2018 we reported a discovery study of a blood biomarker diagnostic test for ASD based on a combination of four plasma protein glycation and oxidation adducts. The test had 88% accuracy in children 5–12 years old. Herein, we present an international multicenter clinical validation study (N = 478) with application of similar biomarkers to a wider age range of 1.5–12 years old children. Three hundred and eleven children with ASD (247 male, 64 female; age 5.2 ± 3.0 years) and 167 children with typical development (94 male, 73 female; 4.9 ± 2.4 years) were recruited for this study at Sidra Medicine and Hamad Medical Corporation hospitals, Qatar, and Hospital Regional Universitario de Málaga, Spain. For subjects 5–12 years old, the diagnostic algorithm with features, advanced glycation endproducts (AGEs)—Nε-carboxymethyl-lysine (CML), Nω-carboxymethylarginine (CMA) and 3-deoxyglucosone-derived hydroimidazolone (3DG-H), and oxidative damage marker, o,o’-dityrosine (DT), age and gender had accuracy 83% (CI 79 – 89%), sensitivity 94% (CI 90–98%), specificity 67% (CI 57–76%) and area-under-the-curve of receiver operating characteristic plot (AUROC) 0.87 (CI 0.84–0.90). Inclusion of additional plasma protein glycation and oxidation adducts increased the specificity to 74%. An algorithm with 12 plasma protein glycation and oxidation adduct features was optimum for children of 1.5–12 years old: accuracy 74% (CI 70–79%), sensitivity 75% (CI 63–87%), specificity 74% (CI 58–90%) and AUROC 0.79 (CI 0.74–0.84). We conclude that ASD diagnosis may be supported using an algorithm with features of plasma protein CML, CMA, 3DG-H and DT in 5–12 years-old children, and an algorithm with additional features applicable for ASD screening in younger children. ASD severity, as assessed by ADOS-2 score, correlated positively with plasma protein glycation adducts derived from methylglyoxal, hydroimidazolone MG-H1 and Nε(1-carboxyethyl)lysine (CEL). The successful validation herein may indicate that the algorithm modifiable features are mechanistic risk markers linking ASD to increased lipid peroxidation, neuronal plasticity and proteotoxic stress.</p

Discovery of a novel cytokine signature for the diagnosis of autism spectrum disorder in young Arab children in Qatar

BackgroundAutism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by impaired social interaction and communication and the occurrence of stereotyped and repetitive behaviors. Several studies have reported altered cytokine profiles in ASD and hence may serve as potential diagnostic biomarkers of the disorder. This study aims to identify diagnostic biomarkers for ASD in a well-defined study cohort in Qatar.MethodsWe measured the protein levels of 45 cytokines in the plasma samples of age- and gender-matched children (2–4 years) with ASD (n = 100) and controls (n = 60) using a Luminex multiplex assay. We compared the differences in the levels of these cytokines between the two study groups and then fitted the significantly altered cytokines into a logistic regression model to examine their diagnostic potential for ASD.ResultsWe found elevated levels of IFN-γ, FGF-2, IL-1RA, and IL-13 and reduced levels of eotaxin, HGF, IL-1 alpha, IL-22, IL-9, MCP-1, SCF, SDF-1 alpha, VEGFA, and IP-10 in the plasma of children with ASD compared to controls. Furthermore, we observed that elevated levels of IFN-γ (odds ratio (OR) = 1.823; 95% (confidence interval) CI = 1.206, 2.755; p = 0.004) and FGF-2 (OR = 2.528; 95% CI = 1.457, 4.385; p &lt; 0.001) were significantly associated with increased odds of ASD, whereas reduced levels of eotaxin (OR = 0.350; 95% CI = 0.160, 0.765; p = 0.008) and HGF (OR = 0.220; 95% CI = 0.070, 0.696; p = 0.010) were significantly associated with lower odds of ASD relative to controls. The combination of these four cytokines revealed an area under the curve (ROC-AUC) of 0.829 (95% CI = 0.767, 0.891; p &lt; 0.001), which demonstrates the diagnostic accuracy of the four-cytokine signature.ConclusionsOur results identified a panel of cytokines that could discriminate between children with ASD and controls in Qatar. In addition, our findings support the predominance of a Th1 immune phenotype in ASD children and emphasize the need to validate these results in larger populations

Novel functions of schizophrenia-related dysbindin-1 in the subventricular zone

Schizophrenia is a neurodevelopmental disorder that has widely been associated with environmental and genetic risk factors. However, direct functional interactions between the two risk factors remain unclear. Therefore, I sought to address how the schizophrenia-related dysbindin-1 may functionally mediate polyI:C-induced inflammation and the importance of this interaction on neurodevelopment in the subventricular zone (SVZ). I focused on the SVZ niche since it lies at the interface between systemic inflammation and neurogenic homeostasis. The interacting effects of dysbindin-1 and polyI:C on microglia, cytokine secretion and leukocyte permeability into the SVZ were also characterised. Multiple systemic polyI:C injections during early postnatal development in dysbindin-1 mutant (Sandy, Sdy) mice resulted in reduced adult SVZ proliferation and reduced neuroblast populations in the rostral migratory stream (RMS). This was also correlated with reduced prepulse inhibition, decreased locomotor activity, object recognition deficit as well as long-term reduction in body weights in adulthood. Postnatal SVZ proliferation was also reduced in Sdy mice given postnatal polyI:C indicating a neurodevelopmental origin of these abnormalities in adulthood. In contrast to these results, adult SVZ proliferation as well as proliferation and neuroblast populations in the RMS were unaffected in transgenic mice overexpressing neuregulin-1 type I (NRG1typeI-tg) and Snap25 mutant (SNAP25+/-) mice that were not immune challenged. I analyzed the expression of toll-like receptor 3 (Tlr3), RelA and Sp1 which are important in the innate immune response and cell proliferation in order to determine how dysbindin-1 and polyI:C mediate their expression. PolyI:C administration to WT SVZ in vivo and in vitro induced the expression of its receptor Tlr3 and the downstream transcription factors RelA and Sp1 indicating a normal inflammatory response. Unexpectedly, in vitro and in vivo polyI:C administration also increased dysbindin-1 expression in WT SVZ, suggesting an inflammatory role for dysbindin-1. This was confirmed in Sdy mice that showed inhibited Tlr3, RelA and Sp1 expression in the SVZ following polyI:C administration both in vivo and in vitro. Furthermore, overexpression of dysbindin-1 (Dtnbp1) gene rescued Tlr3 and RelA expression in vitro in neurospheres prepared from Sdy mice. Supporting the notion that dysbindin-1 regulates immune function, SVZ microglial density was higher in Sdy than in WT mice. Also, more leukocytes were found in the postnatal SVZ of Sdy mice following systemic polyI:C injections than in WT mice given saline. Finally, differential cytokine secretion was detected in Sdy neurospheres in comparison to WT neurospheres under baseline and inflammatory conditions. Taken together, I report novel functions of the schizophrenia-relevant dysbinidin-1 in regulating microglial density in the SVZ, and provide evidence for a direct interaction between dysbindin-1 and polyI:C-induced inflammation that is required for maintaining SVZ proliferation, mediating cytokine secretion and restricting leukocyte infiltration into the SVZ. This work provides a novel mechanistic framework for further studying the relationship between genes and environment in the context of schizophrenia.</p

DataSheet_1_In search of immune cellular sources of abnormal cytokines in the blood in autism spectrum disorder: A systematic review of case-control studies.zip

Abnormal cytokine levels in circulating blood have been repeatedly reported in autism; however, the underlying cause remains unclear. This systematic review aimed to investigate cytokine levels in peripheral blood compartments and identify their potential immune cellular sources in subjects with autism through comparison with controls. We conducted an electronic database search (PubMed, Scopus, ProQuest Central, Ovid, SAGE Journals, and Wiley Online Library) from inception (no time limits) to July 9, 2020, and identified 75 relevant articles. Our qualitative data synthesis focused on results consistently described in at least three independent studies, and we reported the results according to the PRISMA protocol. We found that compared with controls, in subjects with autism, cytokines IL-6, IL-17, TNF-α, and IL-1β increased in the plasma and serum. We also identified monocytes, neutrophils, and CD4+ T cells as potential sources of these elevated cytokines in autism. Cytokines IFN-γ, TGF-β, RANTES, and IL-8 were increased in the plasma/serum of subjects with autism, and IFN-γ was likely produced by CD4+ T cells and natural killer (NK) cells, although conflicting evidence is present for IFN-γ and TGF-β. Other cytokines—IL-13, IL-10, IL-5, and IL-4—were found to be unaltered in the plasma/serum and post-stimulated blood immune cells in autistic individuals as compared with controls. The frequencies of T cells, monocytes, B cells, and NK cells were unchanged in subjects with autism as opposed to controls, suggesting that abnormal cytokines were unlikely due to altered cell numbers but might be due to altered functioning of these cells in autism. Our results support existing studies of abnormal cytokines in autism and provide comprehensive evidence of potential cellular sources of these altered cytokines in the context of autism.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020205224, identifier [CRD42020205224].</p

Characterization of MXene as a Cancer Photothermal Agent Under Physiological Conditions

A growing interest has recently emerged in the use of nanomaterials in medical applications. Nanomaterials, such as MXene, have unique properties due to their 2D ultra-thin structure, which is potentially useful in cancer photothermal therapy. To be most effective, photothermal agents need to be internalized by the cancer cells. In this study, MXene was fabricated using chemical reactions and tested as a photothermal agent on MDA-231 breast cancer cells under static and physiological conditions. Fluid shear stress (∼0.1 Dyn/cm2) was applied using a perfusion system to mimic the physiological tumor microenvironment. The uptake of MXene was analyzed under fluid flow compared to static culture using confocal microscopy, scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), and transmission electron microscopy (TEM). Furthermore, a viability assay was used to assess cell’s survival after exposing the treated cells to photothermal laser at different power densities and durations. We showed that when incubated with cancer cells, 2D MXene nanoparticles were successfully internalized into the cells resulting in increased intracellular temperatures when exposed to NIR laser. Interestingly, dynamic culture alone did not result in a significant increase in uptake suggesting the need for surface modifications for enhanced cellular uptake under shear stress.Qatar Universit

Predictors of morbidity and mortality post emergency abdominal surgery: A national study

Background/Aim: Emergency surgeries have increased in Saudi Arabia. This study examines these surgeries and associated complications. Patients and Methods: This was a prospective multicenter cohort study of patients undergoing emergency intraperitoneal surgery from the eight health sectors of Saudi Arabia. Patients' data were collected over 14 days. Results: In total, 283 patients were included (163 men [54.06%]). The majority of cases were open surgery (204 vs. 79). The 24 h and 30-day mortality rates for the cohort were 0.7 and 2.47%, respectively. Twenty-nine patients (10.24%) required re-intervention, while 19 (8.12%) needed critical care admission. The median length of hospital stay was 3 days. Multivariate analysis showed American Society of Anesthesiologist (ASA) classification score (P = 0.0003), diagnosis (P < 0.0001), stoma formation (P = 0.0123), and anastomotic leak (P = 0.0015) to correlate significantly with 30-day mortality. Conclusion: American Society of Anesthesiologist score, diagnosis, stoma formation and anastomotic leak are associated with 30-day mortality after emergency surgery in Saudi Arabia