Nonlinear Model for Reinforced Concrete under Cyclic Loading

Most of the available shear models for reinforced concrete rely on empirical formulations. In this study, a rational shear stress function is used to define the shear stress–strain envelope for reinforced concrete. Cyclic rules are proposed to define the loading, unloading and reloading relationships for reinforced concrete under shear stress reversals. A normal stress function describing the cyclic relationship of concrete under axial stress is also introduced. The proposed functions are verified using experimental data of reinforced concrete panels tested under monotonic and cyclic loading. Subsequently, the normal and shear stress functions along with their cyclic rules are integrated in a non-linear finite element analysis code. The resulting model accounts for tension stiffening, crack opening and closing, compression hardening and softening, degradation of concrete strength and stiffness in the direction parallel to the crack, compression unloading and reloading, as well as non-linear steel behaviour (strain hardening and Bauschinger effect). The finite element model is then used to analyse two Portland Cement Association shear walls with different geometries tested under cyclic loading. The results show a good agreement between analytical and experimental data. The model showed an excellent capacity of predicting shear deformations of reinforced concrete elements under cyclic loading with minimal computational efforts

Distribution of oil, grease and polycyclic aromatic hydrocarbons in coastal water and sediments of Suez Bay

The permanganate index (PI), oil and grease (O&G), and 17 polycyclic aromatic hydrocarbons (PAHs) were analyzed in surface sediment and water samples collected at 13 sites along the western coast of Suez Bay (SB). PI and O&G in the SB coastal seawater ranged from 9.6 mg O2 l−1 and 17.0 mg l−1 to 16.0 mg O2 l−1 and 37.0 mg l−1, respectively. The level of polycyclic aromatic hydrocarbons (PAH) in water and sediment in the SB offshore area was determined by gas chromatography/flame ionization detection. The concentration ranged from 0.574 to 16873.2 ng g−1 in the sediment and 0.502 to 43.540 ng l−1 in water. The collected data were compared with values reported in the literature. The possible source and origin of pollution was also assessed based on the determined relative PAH levels at the study sites, the ratio of low molecular mass PAHs (LPAHs) to high molecular mass PAHs (HPAHs), and molecular indices of samples.The permanganate index (PI), oil and grease (O&G), and 17 polycyclic aromatic hydrocarbons (PAHs) were analyzed in surface sediment and water samples collected at 13 sites along the western coast of Suez Bay (SB). PI and O&G in the SB coastal seawater ranged from 9.6 mg O2 l−1 and 17.0 mg l−1 to 16.0 mg O2 l−1 and 37.0 mg l−1, respectively. The level of polycyclic aromatic hydrocarbons (PAH) in water and sediment in the SB offshore area was determined by gas chromatography/flame ionization detection. The concentration ranged from 0.574 to 16873.2 ng g−1 in the sediment and 0.502 to 43.540 ng l−1 in water. The collected data were compared with values reported in the literature. The possible source and origin of pollution was also assessed based on the determined relative PAH levels at the study sites, the ratio of low molecular mass PAHs (LPAHs) to high molecular mass PAHs (HPAHs), and molecular indices of samples

Inhibition effect of famotidine towards the corrosion of C-steel in sulphuric acid Solution

The inhibition effect of  famotidine drug  towards  the corrosion of C-steel in 0.5M H2SO4 was studied using weight loss, gasometry, potentiodynamic polarization and electrochemical frequency modulation (EFM) techniques, as well as, surface examination by SEM. The inhibition mechanism of FA is based on the adsorption process forming a film barrier layer protect the steel from acid attack. The adsorption is found to obey Frundlich model. The inhibition efficiency increased by increasing inhibitor concentration and decreased with temperature. Some thermodynamic parameters for adsorption process are deduced and discussed. Keywords: C-steel, famotidine, Adsorption, Corrosion

Proteomic characterisation of drug metabolising enzymes and drug transporters in pig liver

1. Liver enzymes and transporters play an essential role in xenobiotic metabolism, distribution and elimination. Pre-clinical safety assessment relies on studies on animal models, including the (mini)pig. The pig shares many anatomical and physiological characteristics with humans, and there is currently a gap in information about porcine metabolism and disposition pathways and their similarities and differences from human ones.2. Three different sample preparation methods (filter-aided sample preparation (FASP), enhanced FASP (eFASP) and in-solution sample preparation) were used to prepare porcine liver tissue (two samples) for proteomic analysis. The analysis relied on rapid-separation liquid chromatography coupled to Orbitrap mass spectrometry in data-dependent acquisition mode. MASCOT was used for identification and relative label-free quantification was based on spectral counting.3. The three sample preparation methods provided complementary results, allowing characterisation of approximately 70 pharmacologically relevant proteins. The main quantified proteins included 16 cytochrome P450 (CYP) enzymes, 5 UGT enzymes, and 11 transporters. In addition, 20 Phase I and 14 Phase II enzymes were also characterised. Inter-operator differences were negligible and the pig liver pies for CYP, UGT and efflux transporter proteins were established. Human homologues of the quantified CYP, UGT and transporter proteins were identified.<br/

Using age, arterial lactate level and sequential organ failure assessment score in risk stratification of sepsis syndromes

Introduction: In low income countries, ICU places are limited and not all sepsis patients will benefit from ICU admission. Stratification is an important step to identify patients who require ICU treatment from patients who can be treated on general ward setting. Improper stratification results in increased length of stay, costs, morbidity and mortality. Objective: The aim of this study was to stratify the risk of mortality in patients with sepsis syndrome using age, arterial lactate level and SOFA score. Methods: In this prospective observational study, 250 patients with sepsis were enrolled and followed up until discharge. They were categorized into 2 groups according to 7-days mortality. Results: SOFA score (≥5) was the only good tool (AUC=0.722) while age (≥65 years) (AUC=0.650) and arterial lactate (≥3.25 mmol/L) (0.690) were fair tools to predict 7-days mortality. A new score “ALSOFA score” (≥10) was an excellent tool for prediction (AUC =0.912, 95%CI: 0.851 to 0.940, p<0.0001). It showed an excellent sensitivity (90.9%) and specificity (85.1%). Conclusion: In critically ill patients with sepsis syndromes, age, arterial lactate and SOFA score are fair tools of stratification. No single marker/score can be used alone to stratify such patients

Identification of genes differentially expressed in onion infected with Iris yellow spot virus

Iris yellow spot virus (IYSV) causes severe damage and economic losses in onion production. Differential display-PCR was used to study changes in the gene expression of IYSV-infected onion plants. Representative up-regulated and down-regulated genes were selected for further study. Based on sequence analysis, the up-regulated genes were identified as retrotransposon protein, disease resistance-like proteins, chitinase, pathogenesis-related protein, cytochrome oxidase, cytochrome c, pentatricopeptide repeat-containing protein and pectin methylesterase. A DNA-binding transcriptional repressor protein gene was greatly down-regulated. . Most of the identified genes are known to play essential roles in plant defence systems, and are newly identified in onion sequences

Toward systems-informed models for biologics disposition: covariates of the abundance of the neonatal Fc Receptor (FcRn) in human tissues and implications for pharmacokinetic modelling

Biologics are a fast-growing therapeutic class, with intertwined pharmacokinetics and pharmacodynamics, affected by the abundance and function of the FcRn receptor. While many investigators assume adequacy of classical models, such as allometry, for pharmacokinetic characterization of biologics, advocates of physiologically-based pharmacokinetics (PBPK) propose consideration of known systems parameters that affect the fate of biologics to enable a priori predictions, which go beyond allometry. The aim of this study was to deploy a systems-informed modelling approach to predict the disposition of Fc-containing biologics. We used global proteomics to quantify the FcRn receptor [p51 and β2-microglobulin (B2M) subunits] in 167 samples of human tissue (liver, intestine, kidney and skin) and assessed covariates of its expression. FcRn p51 subunit was highest in liver relative to other tissues, and B2M was 1–2 orders of magnitude more abundant than FcRn p51 across all sets. There were no sex-related differences, while higher expression was confirmed in neonate liver compared with adult liver. Trends of expression in liver and kidney indicated a moderate effect of body mass index, which should be confirmed in a larger sample size. Expression of FcRn p51 subunit was approximately 2-fold lower in histologically normal liver tissue adjacent to cancer compared with healthy liver. FcRn mRNA in plasma-derived exosomes correlated moderately with protein abundance in matching liver tissue, opening the possibility of use as a potential clinical tool. Predicted effects of trends in FcRn abundance in healthy and disease (cancer and psoriasis) populations using trastuzumab and efalizumab PBPK models were in line with clinical observations, and global sensitivity analysis revealed endogenous IgG plasma concentration and tissue FcRn abundance as key systems parameters influencing exposure to Fc-conjugated biologics

Special Section on Pediatric Drug Disposition and Pharmacokinetics-Minireview Ontogeny of Hepatic Drug Transporters and Relevance to Drugs Used in Pediatrics

ABSTRACT Most of the pharmacokinetic studies conducted to calculate pediatric drug doses are based on scaling from adult data using various allometric parameters related to body size. However, these uniform scaling methods cannot account for all physiologic changes occurring during maturation, which influence various drugs in different ways. The ontogeny of physiologic and biologic functions accompanying the progression from infancy to childhood to adulthood does not proceed in a simple monotonic rate with body size for various elimination pathways. The transporters and their interplay with enzymes have a substantial role in drug metabolism and disposition. Although much is known about enzymes and their ontogeny, there is a scarcity of information on the ontogenic profile of drug transporters, particularly during the early years of human life. These ontogeny data are required for the enhancement of physiologically based pharmacokinetic models, and consequently for the prediction of pharmacokinetic profiles of new therapeutic compounds in pediatric populations. This review points to the relative ontogeny rate for enzymes and transporters and how these may confound our understanding of the role that transporters may or may not play in childhood compared with adulthood

Biopharmaceutical considerations in paediatrics with a view to the evaluation of orally administered drug products – a PEARRL review.

Objectives: In this review, the current biopharmaceutical approaches for evaluation of oral formulation performance in paediatrics are discussed. Key findings: The paediatric gastrointestinal (GI) tract undergoes numerous morphological and physiological changes throughout its development and growth. Some physiological parameters are yet to be investigated, limiting the use of the existing in vitro biopharmaceutical tools to predict the in vivo performance of paediatric formulations. Meals and frequencies of their administration evolve during childhood and affect oral drug absorption. Furthermore, the establishment of a paediatric Biopharmaceutics Classification System (pBCS), based on the adult Biopharmaceutics Classification System (BCS), requires criteria adjustments. The usefulness of computational simulation and modeling for extrapolation of adult data to paediatrics has been confirmed as a tool for predicting drug formulation performance. Despite the great number of successful physiologically based pharmacokinetic models to simulate drug disposition, the simulation of drug absorption from the GI tract is a complicating issue in paediatric populations. Summary: The biopharmaceutics tools for investigation of oral drug absorption in paediatrics need further development, refinement and validation. A combination of in vitro and in silico methods could compensate for the uncertainties accompanying each method on its own

Randomized, double-blind, placebo-controlled pilot study of metformin as an adjunctive therapy in Parkinson’s disease

BackgroundParkinson’s disease (PD) is caused by the progressive loss of dopaminergic neurons in the substantia nigra. Neuroinflammation is considered a key factor contributing to the pathophysiology of PD. Current gold-standard therapies for PD provide only symptomatic relief without slowing disease progression, highlighting the need to develop new disease-modifying treatments. Metformin has been demonstrated to exert a neuroprotective role in several neurodegenerative disorders including PD.AimThis study aimed to clarify the role of metformin as adjuvant therapy in patients with PD.MethodsSixty patients with PD were divided into 2 groups (n = 30). Patients in group 1 received levodopa/carbidopa (250/25 mg) three times daily for 3 months plus placebo (Control group), while those in group 2 received levodopa/carbidopa (250/25 mg) three times daily and 500 mg metformin two times daily (Metformin group). Patients were assessed via Unified Parkinson’s Disease Rating Scale (UPDRS). The serum concentrations of toll like receptor 4 (TLR-4), α-synuclein, brain derived neurotropic factor (BDNF), and high mobility group box 1 (HMGB-1) were measured before and after treatment.Primary outcomeThe improvement in UPDRS from baseline to 3 months.Secondary outcomeChange in the level of biological markers.ResultsThe control group did not show significant difference in UPDRS when compared to their baseline value by Wilcoxon test (P &gt; 0.05), meanwhile the metformin group showed significant difference when compared to before treatment by Wilcoxon test (P &lt; 0.05). There were no significant differences between the two groups in UPDRS after treatment (P &gt; 0.05) by Man Whitney test. However, the metformin group showed a significant decrease in TLR-4, HMGB-1, and α-synuclein along with a statistically significant increase in BDNF (P &lt; 0.05) when compared to its baseline and control group. The control group did not show any significant changes in all markers when compared to their baseline.ConclusionWhile no significant differences in UPDRS scores were observed between the metformin and control groups, trends in biomarker changes suggest a potential impact of adjunctive metformin use on the underlying pathophysiology of PD. Further studies are needed to assess its effects on motor symptoms over a longer duration.Clinical Trial Registrationidentifier NCT05781711