Transcriptome Analysis of Neuro-2a Cells Treated with Asiatic and Madecassic Acid

Traditional herbal medicine is ingrained as a source of therapeutic compounds to medicate various diseases. The family Araliaceae (Ginseng family) is rich in traditional medicine species, such as Centella asiatica (CA). For many centuries, CA has been used by the indigenous Indian and Chinese in Ayurvedic and traditional medicine, respectively, to improve intelligence, learning, memory, and cognitive performance. Previous studies on cell culture and animal models supported the beneficial effects of CA on the nervous system. However, the exact composition of CA extract and its molecular mechanism that leads to neuroprotection is still unclear. We examined the effect of asiatic acid (AA) and madecassic acid (MA) on neuronal growth, and hypothesized that AA and MA, major neurite promoting factors in CA extract, would induce expression of genes involved in neurite outgrowth and survival. We tested this hypothesis by examining the effects of AA and MA on murine neuroblastoma cells, Neuro-2a (N2a). N2a cells were incubated for two days in a medium containing either 5 µM AA or MA in ethanol or ethanol alone (vehicle). Following incubation, various parameters of neurite outgrowth were measured using NeuronJ software. To explore the impact of AA, MA, and ethanol (vehicle) on neuronal gene expression, transcriptome analysis was used. The results demonstrated that AA and MA facilitate neuronal extension in N2a cultures, and that AA and MA samples had unique transcriptomes compared to the ethanol (vehicle). Furthermore, several of the predicted proteins from the core transcriptome of cells treated with AA and MA have the potential to be involved in neurite outgrowth and related functions

Response Transmissibility for Load Identification Improved By Optimal Sensor Locations

A knowledge of loads acting on a structure is important for analysis and design. There are many applications in which it is difficult to measure directly the dynamic loads acting on a component. In such situations, it may be possible to estimate the imposed loads through a measurement of the system output response. Load identification through output response measurement is an inverse problem that is not only ill-conditioned, but in general leads to multiple solutions. Therefore, additional information, such as number and locations of the imposed loads must be provided ahead of time in order to allow for a unique solution. This dissertation focuses on cases where such information is not readily accessible and presents a method for identification of loads applied to a structure using the concept of response transmissibility. The solution approach is divided into two phases that involve finding the number and location of forces first followed by a reconstruction of the load vector. To achieve the first phase, a complete description of the structure in terms of degrees of freedom needs to be specified and a numerical model, usually a finite element model is built. In order to determine the number of forces and their locations, the proposed algorithm combines the dynamic responses measured experimentally along with the transmissibility matrices obtained from the numerical model. Once the number of loads and their locations are known, a regeneration of the load vector is achieved during the second phase by combining the measured dynamic responses with the transmissibility matrix from the numerical model. In this dissertation, identification of loads through measurement of structural response at a finite number of optimally selected locations is also investigated. Optimum sensor locations are identified using the D-optimal design algorithm. Two different types of measurements are considered, acceleration measurements using accelerometers and the strain measurements using strain gages. A series of simulated results on multi-degree of freedom (MDOF) discrete and continuous systems are presented to illustrate the load identification technique based on response transmissibility. One of the factors that affects the accuracy of load reconstruction is the number of vibration modes included in the analysis, which can be a large number. Improvements using model order reduction, not only help reconstruct the input forces accurately, but it also reduces the computational burden significantly. The developed algorithms are implemented using the finite element tool ANSYS in conjunction with MATLAB software. Numerical sensitivity analysis is also implemented to examine the effect of presence of uncertainties (noise) in experimental data. The results obtained confirm that the techniques presented are robust even in the presence of simulated noise; it is seen that the applied loads are recovered accurately

Motion Transmissibility for Load Identification Based on Optimum Sensor Placement

Knowledge on loads acting on a structure is important for analysis and design. There are many applications in which it is difficult to measure directly the dynamic loads acting on a component. In such situations, it may be possible to estimate the imposed loads through a measurement of the system output response. Load identification through output response measurement is an inverse problem that is not only ill-conditioned but, in general, leads to multiple solutions. Therefore, additional information such as the number and locations of the imposed loads must be provided ahead of time in order to allow for a unique solution. This paper focuses on cases where such information is not readily available and uses the concept of motion transmissibility for the identification of loads applied to a structure. The identification of loads through measurement of structural response at a finite number of optimally selected sensor locations is investigated. Optimum sensor locations are identified using the D-optimal design algorithm to provide the most precise load estimates based on acceleration measurements using accelerometers. Simulation results for multi-degree-of-freedom (MDOF) discrete and continuous systems are presented to illustrate the proposed technique. It is seen that the proposed approach is effective in determining not only the number of applied loads as well as their locations but also the magnitude of applied loads

Study to determine the safety and efficacy of microneedling as an effective treatment for acne vulgaris

Abstract Background Acne is an inflammatory disease of the pilosebaceous unit that occurs primarily in adolescents. There is no current ideal treatment for acne vulgaris, as many mainstay prescription treatment modalities can compromise the skin microbiome or have deleterious health effects. Further research is needed to investigate novel treatment modalities that account for the importance of the skin microbiome. Other developing treatment modalities for acne are still taking a similar mode of action as current treatments by trying to eliminate Cutibacterium acnes despite growing evidence that some C. acnes strains may be symbiotic in nature. The perception that microneedling will exacerbate the disease state and trigger more acneic lesions via the spread of acne‐associated microbes has hindered research investigating whether microneedling is a safe and effective treatment. This pilot clinical study challenges such perceptions by clinical assessment to determine if microneedling may produce beneficial treatment outcomes without disrupting critical skin structure or skin microbiome. Objectives Test the safety and efficacy of microneedling as an effective treatment modality for acne vulgaris. Methods Subjects were split into two groups, one group received three treatments 4 weeks apart, and the second group received four treatments 2 weeks apart. Subjects received an acne assessment by an expert clinical grader at all clinical visits. Results There was a statistically significant reduction in both non‐inflammatory and inflammatory lesions at the 2‐month follow‐up compared to the baseline for Group 1. Group 1 and Group 2 saw a decline of 48.20% and 54.00% in non‐inflammatory lesions and 57.97% and 36.67% in inflammatory lesions, respectively, at their last visit compared to baseline. Conclusion This study expands the utility of microneedling into a potential therapeutic modality for acne vulgaris. The data generated during the duration of this clinical study demonstrates that there is no scientific reason for microneedling to be contraindicated for acne. In this pilot, microneedling did not cause post‐treatment complications and was seen to reduce acne lesions effectively. Thus, microneedling may have the potential to be a well‐tolerated option for those suffering from acne, being a treatment that neither damages the sebaceous glands nor disrupts the skin microbiome

New insight on studying the effect of both chemical sensitivity and rock mechanical properties in shale formation to minimize wellbore instability problems

Historically, many of the wells drilled in in shale formations have experienced a significant rig downtime due to wellbore instabilities. Most of the instability problems originated from the encountered shale formations. The objectives of this study include (1) to measure the properties governing shale strength and drilling fluid/shale interaction, and (2) to establish a reliable and efficient rock mechanical testing procedures related to wellbore stability. Preserved shale core has been recovered from shale formation and special core handling procedure was implemented. Mineral oil was used for plugging and core preservation. Rock mechanical characterization was conducted on core samples using both XRD/SEM techniques to study the core mineralogy. In addition, shale permeability was determined by two methods: flow testing and pressure transition methods. The results indicated that shale has high percentage of quartz (30-40%) which causes the shale to have high porosity and high permeability. The unconfined compressive strength of shale is very low which any drilling fluid that contains water phase further reduces. The Young’s modulus is very low which makes near wellbore deformation high. Based on the shale swelling testing, the all-oil fluid show no volume change occurred to the shale. When the same shale was exposed to the 7% KCl, about 16% increase in core volume occurred in 48 hours. This means that all samples allowed the water to flow into the shale formation

In Vitro Assessment of Salinity Stress Impact on Early Growth in Ten Certified Palestinian Barley Cultivars (Hordeum vulgare L.) Potentially Suitable for Cultivation on Former Quarry Substrates

Salinity is a major constraint for crop health and productivity, particularly on arid, semiarid, and otherwise marginal soils, such as quarry residue. Quarries are a main pillar of national income in Palestine but have a long-lasting toll on the environment. We examined barley (Hordeum vulgare L.), another pillar of the Palestinian economy and one of the most important crops in the world, in this regard for its tolerance to salinity stress. This study is the first to evaluate the impact of salinity (50, 85, 120, and 175 mM NaCl) on seed germination, early growth stage, and morpho-anatomy on ten pre-selected certified Palestinian barley cultivars (Baladi, Improved Baladi, Rihan, ICARDA 1, ICARDA 15, ACSAD 68, ACSAD 176, ACSAD 1417, ACSAD 1732, and ACSAD 1744) to assess their potential for a successful growth start under adverse saline conditions. In addition, soil samples from quarries in Hebron governorate were randomly selected and tested for salinity level, elec-trical conductivity, and total of soluble salts for a first rough overview of options for applying our results, since local data are often scarce or outdated. The examined soil samples reached electrical conductivity (EC) ranges of 1.81 × 10−4–9.071 × 10−4 dS m−1, which are below the normal EC (11–57 × 10−4 dS m−1). This result may contraindicate the hypothesis that quarry lands always suffer from salinity stress. Cultivars such as ACSAD 68 and Icarda 15 proved very sensitive to higher salinity stress with high G50 (time point when 50% of seeds have germinated) at 4.4 d, with 120 mM NaCl (ACSAD 68) or incalculable amounts (Icarda 15) and just 50 and 20% total germination, respec-tively. Concentrations of 175 mM NaCl were found in ACSAD 176 and Improved Baladi (no G50, 37 and 30% germination, respectively). Some cultivars showed a moderate to high resilience to sa-linity, such as ICARDA I, ACSAD 1417, and ACSAD 1744, which reached > 80% seed germination at 120 mM NaCl and >60% at 175 mM NaCl, and G50 within 1.5–2.2 days; the most resilient was ACSAD 1732 with G50 80% at 175 mM NaCl. This is strongly supported by the monitored growth parameters. In conclusion, ACSAD1732 and Icarda 1 cultivars are highly recommended for cultivation in areas of low precipitation and high salt accumulation. In addition, the land and/or soil of quarries, their landfills, and nearby areas in Palestine may be fit for barley cultivation with recommended cultivars regarding salinity stress

Cryoballoon vs radiofrequency ablation of atrial fibrillation: insights from the Veterans Healthcare System

PURPOSE: Catheter ablation is considered the mainstay treatment for drug-refractory atrial fibrillation (AF). The aims of our study were to compare the efficacy and safety of the most two currently approved approaches (point-by-point radiofrequency ablation (RFA), either with contact force (CF) or without contact force (nCF) catheters, and cryoballoon ablation (CBA)) in the Veterans Healthcare System. METHODS: We performed a retrospective study of patients who underwent ablation for treatment of AF at the veterans affairs healthcare system between 2013 and 2018. Only the first reported ablation procedure was included. RESULTS: We included 956 patients in the study (97.4% males, 91.5% Caucasians, 67% paroxysmal AF), with 682 patients in RFA-nCF, 139 in RFA-CF, and 135 in CBA. Thirty-day complication rates were comparable between the three groups with the exception of higher incidence of phrenic nerve injury in CBA group when compared to RFA-nCF (2.2% vs 0.0%, p \u3c 0.01). Long-term recurrence rate of AF was significantly lower in the CBA group when compared to RFA-nCF (33.3% vs 47.7%, adjusted HR 0.60, 95% CI 0.44-0.83, p \u3c 0.01). On the other hand, it was similar between RFA-CF and RFA-nCF groups (43.9% vs 47.7%, adjusted HR 1.01, 95% CI 0.76-1.33, p 0.97). After stratifying patients based on AF type, these findings were only present in patients with paroxysmal AF. CONCLUSION: CBA for paroxysmal AF, in male dominant patients\u27 population, was associated with lower incidence of AF recurrence rate while having a comparable safety profile to RFA independent of the use of CF catheters

Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: What We Already Know

Acute pancreatitis is the most common serious complication of endoscopic retrograde cholangiopancreatography (ERCP) resulting in significant morbidity and occasional mortality. Post-ERCP pancreatitis (PEP) has been recognized since ERCP was first performed, and many studies have shown a consistent risk that must be balanced against the many benefits of this procedure. This review will discuss the pathogenesis, epidemiology, potential risk factors, and clinical presentation of PEP. Moreover, it will discuss in detail the most recent updates of PEP prevention and management