Acute vigabatrin-phenobarbitone-interaction on exploratory behaviour of rats

Vigabatrin (gamma-vinyl GABA) is an irreversible inh:bitor of the enzyme GABA-transaminase (GABA-T) which is responsible for the catabolism of the major inhibitory neurotransmitter gamma- aminobutyric acid (GABA) in the brain. Vigabatrin causes a several fold increase in the levels of brain GABA. The current study investigated further the effects of acute treatment with vigabatrin (100 mgl kg, i.p.) & phenobarbitone sodium (20 mg/kg, i.p.)f alone and in combination, in two rat behavioural models of exploratory activity: the elevated plus-maze model of anxiety and the open field test of locomotor activity. A single injection of vigabatrin or phenobarbitone alone, produced anxiolytic effects in the elevated plus-maze test and increased locomotor activity in the open field test. In contrast, after the concomitant administration of both drugs, the anxiolytic effects were no longer produced in the elevated plus-maze. The increased locomotor activity was also diminished in both tests of exploratory behaviour. These results shed light on the GABA hypothesis of anxiety, insofar as the increased availability of GABA, resulting from either GABA-T inhibition (vigabatrin) or facilitation of GABA-mediated chloride channels (phenobarbitone), seems to result in an increased emotional reactivity which, however, subsequently disappears during combined treatment.peer-reviewe

Tests of Storage Rack Channel Columns with Rear Flanges

An experimental study was performed to investigate the ultimate strength and modes of failure of axially loaded channel rack columns with rear flanges. A total of 16 column specimens fabricated by press-brake forming method were tested up to failure. The material properties of the column specimens were determined using standard tensile coupon tests. The deformation and stress behavior of the tested columns were monitored using displacement transducers and strain gauges. The effects of column slenderness ratio, thickness, perforation, and end conditions on the column ultimate strength and mode of failure were studied. The test failure loads were compared to the ultimate load predictions of the 2001 AISI North American Specification. The comparison showed that the AISI procedure overestimates the failure load, which suggests that the proportioning of the cross-sectional dimensions of the lipped channel sections with rear flanges has a direct effect on the capacity of the columns

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children <18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p<0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p<0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p<0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

Effect Of Local Details And Yield Ratio On Behavior Of Fr Steel Connections

The effect of the local geometric details and yield-to-ultimate stress ratio on the inelastic behavior of pre-Northridge connections is studied through 3D nonlinear finite-element analyses of connection subassemblages. Geometric details considered include shape and size of the access hole and presence or absence of the continuity plate and its thickness. Results from the finite-element analyses highlight the detrimental effect of using steel with the high yield-to-ultimate stress ratio and show that enlarging the size of the access hole to facilitate welding increases the potential for ductile fracture at the root of the access hole. It is suggested that currently recommended provisions for continuity plate thickness could be relaxed for one-sided moment connections

Hierarchically porous, and Cu- and Zn-containing γ-AlOOH mesostrands as adjuvants for cancer immunotherapy

Abstract Alum is the only licensed adjuvant by Food and Drug Administration of USA used in many human vaccines and has excellent safety record in clinical applications. However, alum hardly induces T helper 1 (Th1) immune responses that are required for anti-tumor immunity. In the present study, we fabricated hierarchical copper- and zinc- buds dressing γ-AlOOH mesostrands (Cu- and Zn-AMSs) with randomly wrinkled morphology, mesoscale void- or cave-like pockets, high-exposed surface coverage sites, and positive charge streams in saline. We confirmed that Cu- and Zn-AMSs promoted intracellular uptake of model cancer antigen (ovalbumin, OVA) by THP-1-differentiated macrophage-like cells in vitro. Moreover, Cu- and Zn-AMSs enhanced maturation and cytokine release of bone marrow dendritic cells in vitro. In vivo study demonstrated that Cu- and Zn-AMSs markedly induced anti-tumor-immunity and enhanced CD4 + and CD8 + T cell populations in splenocytes of mice. These findings demonstrated that hierarchical copper- and zinc- buds dressing γ-AlOOH mesostrands, which are oriented in randomly wrinkled matrice, are suitable platforms as novel adjuvants for cancer immunotherapy