Prediction of Diabetes and Prediabetes among the Saudi Population Using a Non-Invasive Tool (AUSDRISK).

Background and Objectives: Screening for type 2 diabetes mellitus (DM2) aims to identify asymptomatic individuals who may be at a higher risk, allowing proactive interventions. The objective of this study was to predict the incidence of DM2 and prediabetes in the Saudi population over the next five years. Materials and Methods: The study was conducted in the Aseer region through August 2023 using a cross-sectional survey for data collection. A multistage stratified random sampling technique was adopted, and data were collected through face-to-face interviews using the validated Arabic version of the Australian Type 2 Diabetes Risk Assessment Tool (AUSDRISK). Results: In total, 652 individuals were included in the study. Their mean age was 32.0 ± 12.0 years; 53.8% were male, 89.6% were from urban areas, and 55.8% were single. There were statistically significant differences between males and females in AUSDRISK items, including age, history of high blood glucose, use of medications for high blood pressure, smoking, physical activity, and measurements of waist circumference (p < 0.05). Based on AUSDRISK scores, 46.2% of the included participants were predicted to develop impaired glucose tolerance within the coming five years (65.8% among females vs. 23.6%), and 21.9% were predicted to develop DM2 (35.6% among males vs. 6.0% among females); this difference was statistically significant (p = 0.0001). Conclusions: Urgent public health action is required to prevent the increasing epidemic of DM2 in Saudi Arabia.

Cytotoxicity and toxicoproteomics analysis of thiazolidinedione exposure in human-derived cardiomyocytes.

Thiazolidinediones (TZDs) (e.g. pioglitazone and rosiglitazone), known insulin sensitiser agents for type II diabetes mellitus, exhibit controversial effects on cardiac tissue. Despite consensus on their association with increased heart failure risk, limiting TZD use in diabetes management, the underlying mechanisms remain uncharacterised. Herein, we report a comprehensive in vitro investigation utilising a novel toxicoproteomics pipeline coupled with cytotoxicity assays in human adult cardiomyocytes to elucidate mechanistic insights into TZD cardiotoxicity. The cytotoxicity assay findings showed a significant loss of mitochondrial adenosine triphosphate production upon exposure to either TZD agents, which may underpin TZD cardiotoxicity. Our toxicoproteomics analysis revealed that mitochondrial dysfunction primarily stems from oxidative phosphorylation impairment, with distinct signalling mechanisms observed for both agents. The type of cell death differed strikingly between the two agents, with rosiglitazone exhibiting features of caspase-dependent apoptosis and pioglitazone implicating mitochondrial-mediated necroptosis, as evidenced by the protein upregulation in the phosphoglycerate mutase family 5-dynamin-related protein 1 axis. Furthermore, our analysis revealed additional mechanistic aspects of cardiotoxicity, showcasing drug specificity. The downregulation of various proteins involved in protein machinery and protein processing in the endoplasmic reticulum was observed in rosiglitazone-treated cells, implicating proteostasis in the rosiglitazone cardiotoxicity. Regarding pioglitazone, the findings suggested the potential activation of the interplay between the complement and coagulation systems and the disruption of the cytoskeletal architecture, which was primarily mediated through the integrin-signalling pathways responsible for pioglitazone-induced myocardial contractile failure. Collectively, this study unlocks substantial mechanistic insight into TZD cardiotoxicity, providing the rationale for future optimisation of antidiabetic therapies.

Toxicometabolomics-based cardiotoxicity evaluation of Thiazolidinedione exposure in human-derived cardiomyocytes.

INTRODUCTION: Thiazolidinediones (TZDs), represented by pioglitazone and rosiglitazone, are a class of cost-effective oral antidiabetic agents posing a marginal hypoglycaemia risk. Nevertheless, observations of heart failure have hindered the clinical use of both therapies. OBJECTIVE: Since the mechanism of TZD-induced heart failure remains largely uncharacterised, this study aimed to explore the as-yet-unidentified mechanisms underpinning TZD cardiotoxicity using a toxicometabolomics approach. METHODS: The present investigation included an untargeted liquid chromatography-mass spectrometry-based toxicometabolomics pipeline, followed by multivariate statistics and pathway analyses to elucidate the mechanism(s)of TZD-induced cardiotoxicity using AC16 human cardiomyocytes as a model, and to identify the prognostic features associated with such effects. RESULTS: Acute administration of either TZD agent resulted in a significant modulation in carnitine content, reflecting potential disruption of the mitochondrial carnitine shuttle. Furthermore, perturbations were noted in purine metabolism and amino acid fingerprints, strongly conveying aberrations in cardiac energetics associated with TZD usage. Analysis of our findings also highlighted alterations in polyamine (spermine and spermidine) and amino acid (L-tyrosine and valine) metabolism, known modulators of cardiac hypertrophy, suggesting a potential link to TZD cardiotoxicity that necessitates further research. In addition, this comprehensive study identified two groupings - (i) valine and creatine, and (ii) L-tryptophan and L-methionine - that were significantly enriched in the above-mentioned mechanisms, emerging as potential fingerprint biomarkers for pioglitazone and rosiglitazone cardiotoxicity, respectively. CONCLUSION: These findings demonstrate the utility of toxicometabolomics in elaborating on mechanisms of drug toxicity and identifying potential biomarkers, thus encouraging its application in the toxicological sciences. (245 words).

Novel Environmentally Friendly Nanomaterials for Drag Reduction of the Emulsified Acid System.

Matrix acidizing is a technique that is widely used in the petroleum industry to remove scales and create channels in the rock. Removal of scales and creation of channels (wormhole) enhance productivity. Conventional acidizing fluids, such as hydrochloric acid (HCl) for carbonate and a mixture of hydrofluoric acid (HF) and HCl acid, are used for the matrix acidizing process. However, these fluids have some drawbacks, including strong acid strength, corrosion at high temperatures, and quick reactions with scale and particles. Emulsified acid systems (EASs) are used to address these drawbacks. EASs can create deeper and narrower wormholes by reducing the reaction rate of the acid due to the external oil phase. However, EASs have a much higher viscosity compared to conventional acidizing fluids. The high viscosity of EASs leads to a high drag that restricts pumping rates and consumes energy. This study aims to utilize environmentally friendly and widely available nanomaterials as drag-reducing agents (DRAs) of the EAS. The nanomaterials used in this study are carbon nanodots (CNDs). CNDs have unique properties and are used in diverse applications in different industries. The size of these CNDs is usually smaller than 10 nm. CNDs are characterized by their biocompatibility and chemical stability. This study investigates the use of CNDs as DRAs for EAS. Several experiments have been conducted to investigate the CNDs as a DRA for the EAS. The developed EAS was initially tested for conductivity and drop-test analysis to ensure the formation of an inverted emulsion. Thereafter, the thermal stability for the range of temperatures and the rheological properties of the EAS were evaluated to meet the criteria of field operation. Then flow experiments with EASs were conducted before and after adding the CNDs to investigate the efficacy of drag reduction of EASs. The results revealed that CNDs can be used as viscosity reducers for the EAS, where adding the CNDs to the EAS reduces the viscosity at two different HCl concentrations (15 and 20%). It reduces the viscosity of the EAS in the presence of corrosion inhibitors as well as other additives to the EAS, showing its compatibility with the field formulation. The drag reduction was observed at the range of temperatures investigated in the study. The conductivity, stability, and rheology experiments for the sample taken after the flow experiment are consistent, ensuring CNDs work as a DRA. The developed EAS with CNDs is robust in terms of field mixing procedures and thermally stable. The CNDs can be used as a DRA with EAS, which will reduce drag in pipes, increasing pumping rates and saving energy.

Surgical confidence when operating among residents in surgery - a cross-sectional study (SCAR study).

BACKGROUND: Self-confidence, is one of the critical variables influencing surgical resident's abilities, and lack of confidence maybe a reason for not entering medical practice immediately. Measuring the level of confidence of senior surgical residents (SSRs) is a crucial step in assessing preparedness to practice. In this study, we aim to measure their confidence level and the factors that might contribute to it. METHODS: Cross-sectional survey conducted at King Abdulaziz University Hospital on SSRs in Saudi Arabia (SA). We approached 142 SSRs, 127 responded. Statistical analysis was performed using RStudio v 3.6.2. Descriptive statistics were performed using counts and percentages for categorical variables and using mean ± standard deviation for continuous variables. Multivariate linear regression (t-statistics) was used to assess the factors associated with confidence in performing essential procedures, while the association between demographics and residency-related factor with the number of completed cases was tested using Chi-square. The level of significance was determined as 0.05. RESULTS: Response rate was 89.4%. Among surveyed residents, 66% had completed < 750 cases as a primary surgeon. More than 90% of SSRs were confident in performing appendectomy, open inguinal hernia repair, laparoscopic cholecystectomy, and trauma laparotomy, while 88% were confident in being on-call in level-I trauma center. No difference was noted in confidence level in relation to the number of performed cases. Residents from the Ministry of Health accounted for 56.3% of the study population and showed a higher confidence level compared to others. 94% of SSRs plan to pursue fellowship training program. CONCLUSION: The study showed that the confidence of SSRs in performing common general surgery procedures was as expected. However, it's important to recognize that confidence doesn't necessarily reflect competence. Considering the majority of SSRs planned to pursue fellowship training programs, it may be time to consider changing the structure of surgical training in SA to a modular format to allow earlier and more intensive exposure.

Determinants of hyperphosphatemia and its relation with hemoglobin levels among hemodialysis patients in two hospitals from Syria: a prospective cross-sectional study.

Hyperphosphatemia and anemia were both associated with several complications in chronic kidney disease (CKD) patients. This study aimed to determine the risk factors of hyperphosphatemia and its relation with anemia among hemodialysis (HD) patients. Secondly, it aimed to determine the prevalence of hyperphosphatemia and anemia. Material and methods: A prospective cross-sectional study was conducted among 146 HD patients from two HD centers in Syria, between June 2021 and March 2022. All patients at least 18 years old on maintenance HD were enrolled. The threshold of phosphorus (phos) level was divided by the upper normal range among HD patients (5.5 mg/dl). We used parametric and nonparametric statistics, the Pearson and Spearman correlations with simple and multiple linear regressions between study variables. Results: 36.9% of patients had a serum phos level of 5.5 or less (norm phos group), and 63.1% of patients had a serum phos level higher than 5.5 (high phos group). Also, 60.9% of patients had hemoglobin (Hb) less than 10 g/dl, and 40.4% of patients had Hb at least 10 g/dl. Age, type of HD access, phos binders (P-binders), parathyroid hormone (PTH), and calcium (Ca) showed significant effects on phos levels. Most patients were using arteriovenous fistula (AVF) (89.7%) as a HD access, and the meantime on HD was higher in the norm phos group compared to the high phos group. In a multivariate and univariate logistic regression analysis, hyperphosphatemia increased with increasing urea (Ur) and creatinine (Cr) levels, while the odds declined with increasing time on HD. Hb did not show a significant relation with phos by using several statistical methods. Discussion/Conclusion: A high prevalence of hyperphosphatemia and anemia was encountered among this sample of HD patients from Syria. There was no correlation between phos and Hb levels in contrast to previous conflicting studies, which mandates future studies to evaluate this correlation and further efforts to determine the range of phos that could have a benefit on anemia with respect to other comorbidities.

Pickering Emulsions Stabilized by Chitosan/Natural Acacia Gum Biopolymers: Effects of pH and Salt Concentrations.

In this study, chitosan (CT) and naturally occurring acacia gum (AG) blends were employed as emulsifiers to form a series of emulsions developed from diesel and water. Effects of pH level (3, 5, 10, and 12) and various NaCl salt concentrations (0.25-1%) on the stability, viscosity, and interfacial properties of CT-(1%)/AG-(4%) stabilized Pickering emulsions were evaluated. Bottle test experiment results showed that the stability indexes of the CT/AG emulsions were similar under acidic (3 and 5) and alkaline (10 and 12) pH media. On the other hand, the effects of various NaCl concentrations on the stability of CT-(1%)/AG-(4%) emulsion demonstrated analogous behavior throughout. From all the NaCl concentrations and pH levels examined, viscosities of this emulsion decreased drastically with the increasing shear rate, indicating pseudoplastic fluid with shear thinning characteristics of these emulsions. The viscosity of CT-(1%)/AG-(4%) emulsion increased at a low shear rate and decreased with an increasing shear rate. The presence of NaCl salt and pH change in CT/AG solutions induced a transformation in the interfacial tension (IFT) at the diesel/water interface. Accordingly, the IFT values of diesel/water in the absence of NaCl/CT/AG (without emulsifier and salt) remained fairly constant for a period of 500 s, and its average IFT value was 26.16 mN/m. In the absence of salt, the addition of an emulsifier (CT-(1%)/AG-(4%)) reduced the IFT to 16.69 mN/m. When the salt was added, the IFT values were further reduced to 12.04 mN/m. At low pH, the IFT was higher (17.1 mN/M) compared to the value of the IFT (10.8 mN/M) at high pH. The results obtained will help understand the preparation and performance of such emulsions under different conditions especially relevant to oil field applications.

Anterior displacement of an avulsed posterio-latero-central tibial plateau fracture repaired with Herbert screws.

Introduction: Tibial plateau fractures are very complex articular fractures with a rare incidence of approximately 10.3%. These fractures may constitute a severe injury to the knee joint and other complications. Presentation of case: A 23- year-old male injured his right knee after a crush accident and was diagnosed with a posterio-latero-central (PLC) sheared fracture of the tibial plateau without an injury to knee ligaments. CT with a reconstruction of the right knee showed that the fracture was accompanied by a free fragment inserted into the anterior compartment of the knee. The free fragment was repositioned to its native location and was fixed with three Herbert screws. Also, we found a peripheral avulsion of the posterio-lateral (PL) portion of the lateral meniscus from the capsular attachment, which was repaired with vicryl absorbable suture. An above knee cast was put in 15-degree flexion for three weeks followed by a restoration of knee movements and weight-bearing after ten weeks of surgery. The patient had a full range of motions and no signs of joint laxity after one year of operation. Discussion conclusion: This study revealed that the surgical repair allowed a quick return to movement for a PLC sheared fracture of the tibial plateau and can be fixed sufficiently to achieve excellent postoperative recovery.

Evaluation of the Dynamic Interfacial Tension between Viscoelastic Surfactant Solutions and Oil Using Porous Micromodels.

Interfacial tension (IFT) is a crucial parameter in many natural and industrial processes, such as enhanced oil recovery and subsurface energy storage. IFT determines how easy the fluids can pass through pore throats and hence will decide how much residual fluids will be left behind. Here, we use a porous glass micromodel to investigate the dynamic IFT between oil and Armovis viscoelastic surfactant (VES) solution based on the concept of drop deformation while passing through a pore throat. Three different concentrations of VES, that is, 0.5, 0.75, and 1.25% vol% prepared using 57 K ppm synthetic seawater, were used in this study. The rheology obtained using a rheometer at ambient temperature showed zero shear viscosity of 325, 1101, and 1953 cP for 0.5%, 0.75%, and 1.25% VES, respectively, with a power-law region between 2 and 50 1/s. The dynamic IFT increases with the shear rate and then reaches a plateau. The results of IFT were compared with those obtained from the spinning drop method, which shows 97% accuracy for 1.25% VES, whereas the accuracy decreased to 65% for 0.75 VES and 51% for 0.5% VES. The findings indicate that we can reliably estimate the IFT of VES at higher concentrations directly during multiphase flow in porous micromodels without the need to perform separate experiments and wait for a long time to reach equilibrium.

Enhancing the Oil Recovery from Naturally Fractured Reservoirs Using Viscoelastic Surfactant (VES) Flooding: A Field-Scale Simulation.

A viscoelastic surfactant (VES) has the combined properties of a surfactant and a polymer. Injection of VES fluids into naturally fractured reservoirs (NFRs) can control the mobility of the injected fluid and enhance the total oil recovery. This paper presents a field-scale simulation to evaluate the performance of a noble VES fluid in enhancing the oil recovery from a naturally fractured reservoir. In this work, the results of coreflooding, computerized tomography (CT)-scan, rheology, interfacial tension (IFT), and adsorption measurements were used to build and calibrate a lab-scale model. Thereafter, a chemical enhanced oil recovery (EOR) modeling simulator developed by a computer modeling group (CMG-STARS) was used to build a field-scale simulation. Real seismic data, permeability and porosity distributions, and operating conditions were utilized to develop and evaluate the simulation model. The results show that VES can outperform the surfactant-polymer (SP) flooding and waterflooding in NFRs; VES improved the oil recovery by 10% and reduced the water cut by 47%, at the same conditions. VES reduced the IFT by two orders of magnitude (100 times) compared to waterflooding. Also, VES altered the rock wettability to a more water-wet status, leading to reduce the relative permeability to water (K rw) by a factor of 10, on average. Finally, the simulation study indicated that applying waterflooding after VES flooding leads to a minor increase in the oil recovery. Overall, this study provides a detailed comparison between VES flooding, SP flooding, and conventional waterflooding in NFRs. Sensitivity analysis was performed to study the impact of treatment parameters on the oil recovery from naturally fractured reservoirs. Using actual NFR data, the optimum VES flooding was determined, which will help in conducting VES flooding for real EOR operations.

Application of a Pickering Emulsified Polymeric Gel System as a Water Blocking Agent.

The conventional methods for controlling excess water production in oil/gas wells can be classified on the basis of the mechanism (pore-blocking mechanism and relative permeability modification) used. Gel systems developed on the basis of a pore-blocking mechanism completely block the pores and stop the flow of both oil and water, whereas a relative permeability modifier (RPM) only restricts the flow of a single phase of the fluid. The gel working on the basis of the pore-blocking mechanism is known as a total blocking gel. An invert emulsified (PAM-PEI) polymer gel is a relative permeability modifier system. The same invert emulsion system is tested as a total blocking gel system in this research work. The dual-injection technique (1st injection and 2nd injection) was used for this purpose. In this research work, the emulsion system was tested at a temperature of 105 °C. The core sections with drilled holes and fractures were used for the core flooding experiments, representing a highly fractured reservoir. The developed emulsified gel system was characterized using a dilution test, an inverted bottle test, microscopic images, and FTIR images. The emulsified polymer gel was tested using a core flooding experiment. After the 2nd injection, the postflood medical CT and micro-CT images of the core sections clearly showed the presence of two different phases in the core section, i.e., the oil phase and the gel phase. The core flooding experiment result indicates that the gel formed after the 2nd injection of the emulsion system can withstand a very high differential pressure, i.e., above 2000 psi. The gel did not allow any oil or water to be produced. Hence, the developed emulsified polymer gel system with the help of a dual-injection technique can be efficiently used as a total blocking gel for high-temperature reservoirs.

Salivary pH changes under the effect of stainless steel versus elastomeric ligatures in fixed orthodontic patients: a single-center, randomized controlled clinical trial.

BACKGROUND: Fluctuations in pH of saliva during a prolonged treatment course influences the enamel demineralization progress, which is one of the complications of fixed orthodontic treatment. This randomized clinical trial aimed to evaluate and compare the short-term effects of stainless steel (SS) versus elastomeric (EM) ligatures on salivary pH in patients scheduled for fixed orthodontic treatment. METHODS: Seventy participants were enrolled in the study (54 female, 16 male) aged 19-36 years who met specific inclusion criteria. They were randomly selected and allocated into two equal groups through computer-generated randomization. All patients received fixed orthodontic treatment using conventional orthodontic brackets. Two commonly used archwire ligature methods were used: SS and EMs. An unstimulated (resting) salivary sample was collected before tying of the ligatures at T0 (baseline), 2 weeks, 6 (weeks), and 12 (weeks). Salivary pH was measured using a digital pH meter. The level of significance was set at p value < 0.05. RESULTS: The salivary pH level was stable between T0 and T1 (6.72 ± 0.14), then significantly and progressively increased from T1 to T2 (6.78 ± 0.13) and from T2 to T3 (6.81 ± 0.14) with (p < 0.05) in the SS group. In the EM group, the salivary pH level was significantly decreased in all follow-up periods; T0 (6.77 ± 0.16), T1 (6.72 ± 0.14), T2 (6.67 ± 0.13) and T3 (6.64 ± 0.13). CONCLUSION: The EM ligatures showed a significant decrease in salivary pH to an unfavorable level, which increased the risk of enamel demineralization. Therefore, EMs as ligature material is preferably should not be recommended in patients with high caries index or inadequate oral hygiene. Trial registration ANZCTR.org. (ACTRN12618001647224) http://www.anzctr.org.au/ACTRN12618001647224.aspx . Registration Date: 5/10/2018, "Retrospectively registered".

Synthesis and Testing of Monoethylene Glycol Carbon Quantum Dots for Inhibition of Hydrates in CO2 Sequestration.

The hydrate formation during the transportation and injection of carbon dioxide in pipelines always leads to the risk of plugging. The development of a cost-efficient CO2 sequestration method requires efficient hydrate inhibitors. In this research work, the synthesized carbon quantum dots (CQDs) of monoethylene glycol (MEG) were tested with CO2 hydrates for their hydrate inhibition efficiency. The hydrothermal method was used for the synthesis of CQDs. The synthesized CQDs were characterized using UV light (365 nm), UV-vis absorption, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and photoluminescence (PL) spectroscopy. MEG CQDs were found to have very good water solubility and fluorescence properties. The MEG CQDs were tested for their CO2 hydrate inhibition efficiency using the sapphire rocking cell unit. Test results proved that MEG CQDs are much more effective as a CO2 hydrate inhibitor in comparison to MEG.

Deducing the Relation between Viscosity and Oil-Induced Structural Changes of Viscoelastic Surfactants Using a Kinetic Approach.

The present study relates viscosity reduction with time of a wormlike micellar solution to the micellar transitions that occur with time in the presence of three n-alkanes, namely, n-decane, n-dodecane, and n-hexadecane. Steady-shear rheology and small-angle X-ray scattering were used to deduce the relationship. The effect of n-alkane concentration was tested only with n-decane. There were at most three stages of viscosity reduction, which appeared in the following order: (i) the rising viscosity stage, (ii) the fast viscosity reduction stage, and (iii) the low-viscosity stage. The stages and rates of viscosity transition depended on the type of micelles present and the degree of micelle entanglement. Moreover, the rate of transition increased when the n-alkane concentration was increased and when the n-alkane molecular mass was reduced. n-Hexadecane induced only the first two stages of transition at a slower rate compared to the other oils.

TCA cycle metabolic compromise due to an aberrant S-nitrosoproteome in HIV-associated neurocognitive disorder with methamphetamine use.

In the brain, both HIV-1 and methamphetamine (meth) use result in increases in oxidative and nitrosative stress. This redox stress is thought to contribute to the pathogenesis of HIV-associated neurocognitive disorder (HAND) and further worsening cognitive activity in the setting of drug abuse. One consequence of such redox stress is aberrant protein S-nitrosylation, derived from nitric oxide, which may disrupt normal protein activity. Here, we report an improved, mass spectrometry-based technique to assess S-nitrosylated protein in human postmortem brains using selective enrichment of S-nitrosocysteine residues with an organomercury resin. The data show increasing S-nitrosylation of tricarboxylic acid (TCA) enzymes in the setting of HAND and HAND/meth use compared with HIV+ control brains without CNS pathology. The consequence is systematic inhibition of multiple TCA cycle enzymes, resulting in energy collapse that can contribute to the neuronal and synaptic damage observed in HAND and meth use.

Soluble α-synuclein-antibody complexes activate the NLRP3 inflammasome in hiPSC-derived microglia.

Parkinson's disease is characterized by accumulation of α-synuclein (αSyn). Release of oligomeric/fibrillar αSyn from damaged neurons may potentiate neuronal death in part via microglial activation. Heretofore, it remained unknown if oligomeric/fibrillar αSyn could activate the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome in human microglia and whether anti-αSyn antibodies could prevent this effect. Here, we show that αSyn activates the NLRP3 inflammasome in human induced pluripotent stem cell (hiPSC)-derived microglia (hiMG) via dual stimulation involving Toll-like receptor 2 (TLR2) engagement and mitochondrial damage. In vitro, hiMG can be activated by mutant (A53T) αSyn secreted from hiPSC-derived A9-dopaminergic neurons. Surprisingly, αSyn-antibody complexes enhanced rather than suppressed inflammasome-mediated interleukin-1ß (IL-1ß) secretion, indicating these complexes are neuroinflammatory in a human context. A further increase in inflammation was observed with addition of oligomerized amyloid-ß peptide (Aß) and its cognate antibody. In vivo, engraftment of hiMG with αSyn in humanized mouse brain resulted in caspase-1 activation and neurotoxicity, which was exacerbated by αSyn antibody. These findings may have important implications for antibody therapies aimed at depleting misfolded/aggregated proteins from the human brain, as they may paradoxically trigger inflammation in human microglia.

Rapid Determination of Emulsion Stability Using Turbidity Measurement Incorporating Artificial Neural Network (ANN): Experimental Validation Using Video/Optical Microscopy and Kinetic Modeling.

Determination of emulsion stability has important applications in crude oil production, separation, and transportation. The turbidimetry method offers advantage of rapid determination of stability at a relatively low cost with good accuracy. In this study, the stability of an oil-in-water (O/W) emulsion prepared by dispersing heavy oil particles in the aqueous solution containing poly(vinyl alcohol) (PVA) has been determined using turbidity measurements. The turbidimetry theory of emulsion stability has been validated using experimental data of turbidity at different wavelengths (350-800 nm) and storage times (0-300 min). The artificial neural network (ANN) has been found to give good predictive performance of the turbidity data. The characteristic change in turbidity has been supported using particle size and distribution analyses performed using optical/video microscopy. The results obtained from the turbidimetry correlation show that the emulsion destabilization rate constant (κ', min-1) is in the range of 0.01-0.04 min-1 (at wavelengths between 350 and 800 nm, respectively). The rate constant remains unchanged (κ' = 0.02 min-1) between the wavelength of 375 and 650 nm. In addition, the demulsification rate constant (κ' = 0.015 min-1) obtained from kinetic modeling using the bottle test is in close agreement with this value. The overall findings ultimately revealed that the turbidimetry method could be used to determine stability of typical O/W emulsions with an acceptable level of accuracy.

NitroSynapsin ameliorates hypersynchronous neural network activity in Alzheimer hiPSC models.

Beginning at early stages, human Alzheimer's disease (AD) brains manifest hyperexcitability, contributing to subsequent extensive synapse loss, which has been linked to cognitive dysfunction. No current therapy for AD is disease-modifying. Part of the problem with AD drug discovery is that transgenic mouse models have been poor predictors of potential human treatment. While it is undoubtedly important to test drugs in these animal models, additional evidence for drug efficacy in a human context might improve our chances of success. Accordingly, in order to test drugs in a human context, we have developed a platform of physiological assays using patch-clamp electrophysiology, calcium imaging, and multielectrode array (MEA) experiments on human (h)iPSC-derived 2D cortical neuronal cultures and 3D cerebral organoids. We compare hiPSCs bearing familial AD mutations vs. their wild-type (WT) isogenic controls in order to characterize the aberrant electrical activity in such a human context. Here, we show that these AD neuronal cultures and organoids manifest increased spontaneous action potentials, slow oscillatory events (~1 Hz), and hypersynchronous network activity. Importantly, the dual-allosteric NMDAR antagonist NitroSynapsin, but not the FDA-approved drug memantine, abrogated this hyperactivity. We propose a novel model of synaptic plasticity in which aberrant neural networks are rebalanced by NitroSynapsin. We propose that hiPSC models may be useful for screening drugs to treat hyperexcitability and related synaptic damage in AD.

Molecular Fractionation in the Organic Materials of Source Rocks.

Hydrocarbons that are transported in a hierarchal path from the nanoporous constituents of a shale matrix to natural and then hydraulic fractures are subject to continuous fractionation during the journey. The organic nanopores of a source rock matrix known as kerogen have pore sizes on the angstrom scale. At that degree of confinement, pores can act as a selective membrane, preferentially maintaining some components over the others in a continuous fractionation phenomenon that alters the adsorption/desorption isotherm. Several studies have considered the adsorption/desorption behavior of kerogen on the basis of a single component. In reality, methane is associated with other hydrocarbons, making that assumption questionable. The present work investigates the multicomponent gas sorption of kerogen structures via a molecular computational approach. The continuous fractionation results in the accumulation of heavier components. The compositional changes alter the phase behavior, enlarging the anticipated two-phase regime. Additionally, the ability of molecules to diffuse from kerogen was also found to be affected by the fractionation effect. These microscale effects provide some insights into the potential factors that influence the productivity at the reservoir scale.