Effect Of Treatment Research Articles

Long-term Outcome of Asymptomatic Esophageal Eosinophilia.

: Asymptomatic esophageal eosinophilia (aEE), characterized by eosinophil infiltration in the esophagus without clinical symptoms, has been reported as a precursor of eosinophilic esophagitis (EoE). Nevertheless, no report exists on the long-term clinical course of the disease. Therefore, this study aimed to investigate the long-term clinical course of aEE over 5 years, including the symptomatic conversion rate and the effect of treatments. : We reviewed 28 patients with aEE who had been followed up for over 5 years with endoscopic monitoring. The basal characteristics of patients were compared with those of 58 patients diagnosed with EoE during the same period. Patients' clinicopathological findings were collected and examined. : No significant differences in basal characteristics and histopathological findings were observed between the patients with aEE and those with EoE. The median follow-up duration was 64 months. Among the 28 patients with aEE, seven were treated with proton pump inhibitor or potassium-competitive acid blocker and the remaining 21 opted for follow-up with no medication. Among the treated patients, six (85.7%) exhibited endoscopic and pathologic improvements. Among the cases followed up without medication, the findings worsened in two (9.5%), improved spontaneously in seven (33.3%), and were unchanged in 12 (57.1%), and three (14.3%) developed symptoms at a mean time of 40 months. Symptoms developed in cases where endoscopic and pathologic findings remained unchanged or worsened during follow-up. : Some patients with aEE had improved findings without treatment, whereas others developed symptoms, emphasizing the importance of long-term monitoring and individualized treatment decisions.

Cy3-based nanoviscosity determination of mucus: Effect of mucus collection methods and antibiotics treatment.

The integrity of the protective mucus layer as a primary defense against pathogen invasion and microbial leakage into the intestinal epithelium can be compromised by the effects of antibiotics on the commensal microbiome. Changes in mucus integrity directly affect the solvent viscosity in the immediate vicinity of the mucin network, i.e., the nanoviscosity, which in turn affects both biochemical reactions and selective transport. To assess mucus nanoviscosity, a reliable readout via the viscosity-dependent fluorescence lifetime of the molecular rotor dye Cy3 is established and nanoviscosities from porcine and murine ex vivo mucus are determined. To account for different mucin concentrations due to the removal of digestive residues during mucus collection, the power law dependence of mucin concentration on viscosity is used. The impact of antibiotics combinations (meropenem/vancomycin, gentamycin/ampicillin) on ex vivo intestinal mucus nanoviscosity is presented. The significant increase in viscosity of murine intestinal mucus after treatment suggests an effect of antibiotics on the microbiota that affects mucus integrity. The presented method will be a useful tool to assess how drugs, directly or indirectly, affect mucus integrity. Additionally, the method can be utilized to analyze the role of mucus nanoviscosity in health and disease, as well as in drug development. This article is protected by copyright. All rights reserved.

Mesenchymal Stem Cells Regulate Microglial Polarization via Inhibition of the HMGB1/TLR4 Signaling Pathway in Diabetic Retinopathy.

Diabetic retinopathy (DR) is recognized as the most prevalent retinal degenerative disorder. Inflammatory response usually precedes microvascular alteration and is the primary factor of diabetic retinopathy. Activated microglia express many pro-inflammatory cytokines that exacerbate retina inflammation and disruption. In the present study, we found that MSCs alleviated blood-retina barrier (BRB) breakdown in diabetic rats, as evidenced by reduced retinal edema, decreased vascular leakage, and increased occludin expression. The MSC-treated retinal microglia exhibited reduced expression of M1-phenotype markers in the diabetic rats, including inducible nitric oxide synthase (iNOS), CD16, and pro-inflammatory cytokines. On the other hand, MSCs increased the expression of M2-phenotype markers, such as arginase-1 (Arg-1), CD206, and anti-inflammatory cytokines. HMGB1/TLR4 signaling pathway is activated in DR and inhibited after MSC treatment. Consistent with in vivo evidence, MSCs drove BV2 microglia toward M2 phenotype in vitro. Overexpression of HMGB1 in microglia reversed the effects of MSC treatment, suggesting HMGB1/TLR4 pathway is necessary for MSCs' regulatory effects on microglia polarization. Collectively, MSCs exert beneficial effects on DR by polarizing microglia from M1 toward M2 phenotype via inhibiting the HMGB1/TLR4 signaling pathway.

Clinical features, treatment, and follow-up of OPPG and high-bone-mass disorders: LRP5 is a key regulator of bone mass.

Low-density lipoprotein receptor-related protein 5 (LRP5) is involved in the canonical Wnt signaling pathway. The gain-of-function mutation leads to high bone mass (LRP5-HBM), while the loss-of-function mutation leads to osteoporosis-pseudoglioma syndrome (OPPG). In this study, the clinical manifestations, disease-causing mutations, treatment, and follow-up were summarized to improve the understanding of these two diseases. Two OPPG patients and four LRP5-HBM patients were included in this study. The clinical characteristics, biochemical and radiological examinations, pathogenic mutations, and structural analysis were summarized. Furthermore, several patients were followed up to observe the treatment effect and disease progress. Congenital blindness, persistent bone pain, low bone mineral density (BMD), and multiple brittle fractures were the main clinical manifestations of OPPG. Complex heterozygous mutations were detected in two OPPG patients. The c.1455G > T mutation in exon 7 was first reported. During the follow-up, BMD of two patients was significantly improved after bisphosphonate treatment. On the contrary, typical clinical features of LRP5-HBM included extremely high BMD without fractures, torus palatinus and normal vision. X-ray showed diffuse osteosclerosis. Two heterozygous missense mutations were detected in four patients. In addition, age-related bone loss was found in one LRP5-HBM patient after 12-year of follow-up. This study deepened the understanding of the clinical characteristics, treatment, and follow-up of OPPG and LRP5-HBM; expanded the pathogenic gene spectrum of OPPG; and confirmed that bisphosphonates were effective for OPPG. Additionally, it was found that Ala242Thr mutation could not protect LRP5-HBM patients from age-related bone loss. This phenomenon deserves further study.

Effect of Elicitor Treatments on Quality Attributes in Blueberry: Implications of Cultivar and Environmental Conditions

Elicitors of plant defence responses can trigger defence mechanisms that are able to protect plant tissues from biotic or abiotic stresses. Since one defence response involves the activation of secondary metabolites’ biosynthesis, the purpose of this study was to evaluate the effect of chitosan and melatonin pre-harvest treatments on the quality and the nutritional parameters of the fruits of blueberry (Vaccinium corymbosum L.). Across the two years of experiment, three different cultivars (cv.s. ‘Cosmopolitan’, ‘Hortblue Poppins’ and ‘Legacy’) were treated with 1% chitosan or 100 µM melatonin every two weeks during the ripening season and ripe fruits were progressively harvested and analysed. The treatment with both elicitors had only slight effects on dry matter, soluble solids content, titratable acidity and pH, with a cultivar-dependent response. On the other hand, elicitors significantly affected the levels of phenylpropanoid and antioxidant compounds in all cvs. in both years, with a higher accumulation of total anthocyanins and phenolics and the enhancement of the antioxidant capacity, with positive effects on the nutraceutical quality of fruits. The anthocyanin profile in terms of both absolute concentrations and the relative proportion of single anthocyanins was affected by both harvest year and cv., highlighting the role of the genetic background in the plant response to environmental conditions (with particular reference to summer heat stress) and to elicitor treatments.

An opportunity for post‐harvest seafood safety: atmospheric pressure air or helium cold plasma to control Salmonella Enteritidis in sea bass

SummarySalmonella contamination of fish after harvest is a significant food safety risk. To control this risk, it was aimed to reduce Salmonella Enteritidis in sea bass by helium and air plasma. Considering that preserving the fresh properties of sea bass is important for industrial applicability, determining the sensory effects of plasma treatments was also aimed. Since air plasma would provide a cheaper and easier alternative to helium plasma, their effects were compared. Additionally, the in vitro effects of these treatments on Salmonella Enteritidis were also investigated. Air and helium plasma completely inhibited the initial load of S. Enteritidis (2.79 Log CFU) inoculated on agar surface after 10 min treatment. Then, the inoculated sea bass samples were exposed to air or helium plasma for durations ranging from 1 to 15 min. Air and helium plasma treatments for 10 min provided 0.90 log cfu g−1 and 1.13 Log CFU/g reductions, respectively, but longer treatments did not lead to further significant reductions. Sensory scores were all above 7 (good) when samples were treated with air or helium plasma for 1–10 min, but longer treatments resulted in lower scores. The reduction of S. Enteritidis and changes in sensory characteristics were interpreted together and it was concluded that 10 min of air or helium plasma provided maximum reduction without causing any significant sensory changes. Overall, the current study showed that atmospheric pressure air and helium plasmas can be useful for ensuring post‐harvest safety in the fish trade.

Finding the best subgroup with differential treatment effect with multiple outcomes.

Precision medicine aims to identify specific patient subgroups that may benefit the most from a particular treatment than the whole population. Existing definitions for the best subgroup in subgroup analysis are based on a single outcome and do not consider multiple outcomes; specifically, outcomes of different types. In this article, we introduce a definition for the best subgroup under a multiple-outcome setting with continuous, binary, and censored time-to-event outcomes. Our definition provides a trade-off between the subgroup size and the conditional average treatment effects (CATE) in the subgroup with respect to each of the outcomes while taking the relative contribution of the outcomes into account. We conduct simulations to illustrate the proposed definition. By examining the outcomes of urinary tract infection and renal scarring in the RIVUR clinical trial, we identify a subgroup of children that would benefit the most from long-term antimicrobial prophylaxis.

On variance estimation of the inverse probability-of-treatment weighting estimator: A tutorial for different types of propensity score weights.

Propensity score methods, such as inverse probability-of-treatment weighting (IPTW), have been increasingly used for covariate balancing in both observational studies and randomized trials, allowing the control of both systematic and chance imbalances. Approaches using IPTW are based on two steps: (i) estimation of the individual propensity scores (PS), and (ii) estimation of the treatment effect by applying PS weights. Thus, a variance estimator that accounts for both steps is crucial for correct inference. Using a variance estimator which ignores the first step leads to overestimated variance when the estimand is the average treatment effect (ATE), and to under or overestimated estimates when targeting the average treatment effect on the treated (ATT). In this article, we emphasize the importance of using an IPTW variance estimator that correctly considers the uncertainty in PS estimation. We present a comprehensive tutorial to obtain unbiased variance estimates, by proposing and applying a unifying formula for different types of PS weights (ATE, ATT, matching and overlap weights). This can be derived either via the linearization approach or M-estimation. Extensive R code is provided along with the corresponding large-sample theory. We perform simulation studies to illustrate the behavior of the estimators under different treatment and outcome prevalences and demonstrate appropriate behavior of the analytical variance estimator. We also use a reproducible analysis of observational lung cancer data as an illustrative example, estimating the effect of receiving a PET-CT scan on the receipt of surgery.

RNA-sequencing exploration on SIR2 and SOD genes in Polyalthia longifolialeaf methanolic extracts (PLME) mediated anti-aging effects in Saccharomyces cerevisiaeBY611 yeast cells.

Polyalthia longifolia is well-known for its abundance of polyphenol content and traditional medicinal uses. Previous research has demonstrated that the methanolic extract of P. longifolia leaves (PLME, 1mg/mL) possesses anti-aging properties in Saccharomyces cerevisiae BY611 yeast cells. Building on these findings, this study delves deeper into the potential antiaging mechanism of PLME, by analyzing the transcriptional responses of BY611 cells treated with PLME using RNA-sequencing (RNA-seq) technology. The RNA-seq analysis results identified 1691 significantly (padj < 0.05) differentially expressed genes, with 947 upregulated and 744 downregulated genes. Notably, the expression of three important aging-related genes, SIR2, SOD1, and SOD2, showed a significant difference following PLME treatment. The subsequent integration of these targeted genes with GO and KEGG pathway analysis revealed the multifaceted nature of PLME's anti-aging effects in BY611 yeast cells. Enriched GO and KEGG analysis showed that PLME treatment promotes the upregulation of SIR2, SOD1, and SOD2 genes, leading to a boosted cellular antioxidant defense system, reduced oxidative stress, regulated cell metabolism, and maintain genome stability. These collectively increased longevities in PLME-treated BY611 yeast cells and indicate the potential anti-aging action of PLME through the modulation of SIR2 and SOD genes. The present study provided novel insights into the roles of SIR2, SOD1, and SOD2 genes in the anti-aging effects of PLME treatment, offering promising interventions for promoting healthy aging.

Effect of Heat Treatment on Magnetic Properties of EN8D Steel Used in Automotive Applications

The present study focuses on achieving the optimum combination of mechanical and magnetic properties for EN8D steel. SAE 1010 and EN8D steels are the candidate materials to manufacture the fixed nucleus of the disk-type electro-mechanical horn. Both materials have either good magnetic or mechanical properties. The main function of fixed nucleus is to get magnetized and pull the mobile nucleus towards it. However, as magnetization and demagnetization take place in the range of 300-500 Hz, fixed and mobile nucleus continuously strikes each other at high frequency. Due to such high frequency working condition, fixed nucleus is prone to failure under wear and tear or under fatigue. For this kind of application, a combination of magnetic and mechanical properties is required in the material used to manufacture fixed nucleus. Thus, in current paper, the effects of chemical composition, microstructure, hardness, strength and toughness of EN8D steel before and after austenizing and tempering heat treatment are evaluated and compared with as-rolled EN8D and SAE 1010 steels, which are mostly used for manufacturing fixed nucleus. Magnetic permeability was evaluated using JMatPro software and compared. Austenizing treatment is performed at 900 °C for 1 hour, followed by water quenching. Tempering treatment of the same was performed at 550 °C for 2.5 hours. The Ultimate Tensile Strength (UTS) and hardness of EN8D after heat treatment decreased from 917 to 781 MPa and 269 to 233 HV0.1 respectively. Charpy V-Notch (CVN) toughness of EN8D steel after heat treatment increased from 12 to 45 joules. It indicates that the decrease in strength and hardness resulted into increase in toughness. Microstructure changes from ferrite and pearlite to combination of tempered martensite, ferrite and bainite. Magnetic permeability evaluated by JMatPro software shows increment from 450 to 564 Gauss/Oersted in EN8D steel after heat treatment.&#x0D; Keywords: Electro-mechanical horn, fixed nucleus, magnetic permeability, JMatPro, SAE1010 steel, EN8D steel

Long-Term Protective Effects of Succinate Dehydrogenase Inhibition during Reperfusion with Malonate on Post-Infarction Left Ventricular Scar and Remodeling in Mice

Succinate dehydrogenase inhibition with malonate during initial reperfusion reduces myocardial infarct size in both isolated mouse hearts subjected to global ischemia and in in situ pig hearts subjected to transient coronary ligature. However, the long-term effects of acute malonate treatment are unknown. Here, we investigated whether the protective effects of succinate dehydrogenase inhibition extend to a reduction in scar size and adverse left ventricular remodeling 28 days after myocardial infarction. Initially, ten wild-type mice were subjected to 45 min of left anterior descending coronary artery (LAD) occlusion, followed by 24 h of reperfusion, and were infused during the first 15 minutes of reperfusion with saline with or without disodium malonate (10 mg/Kg/min, 120 μL/Kg/min). Malonate-treated mice depicted a significant reduction in infarct size (15.47 ± 3.40% of area at risk vs. 29.34 ± 4.44% in control animals, p &lt; 0.05), assessed using triphenyltetrazolium chloride. Additional animals were then subjected to a 45 min LAD ligature, followed by 28 days of reperfusion. Treatment with a single dose of malonate during the first 15 min of reperfusion induced a significant reduction in scar area, measured using Picrosirius Red staining (11.94 ± 1.70% of left ventricular area (n = 5) vs. 23.25 ± 2.67% (n = 9), p &lt; 0.05), an effect associated with improved ejection fraction 28 days after infarction, as determined using echocardiography, and an attenuated enhancement in expression of the pro-inflammatory and fibrotic markers NF-κB and Smad2/3 in remote myocardium. In conclusion, a reversible inhibition of succinate dehydrogenase with a single dose of malonate at the onset of reperfusion has long-term protective effects in mice subjected to transient coronary occlusion.

In vivo evidence of sea buckthorn relieving oxidative stress and improving immune performance of common carp (Cyprinus carpio L.).

Sea buckthorn has the functions of anti-oxidation, anti-tumor, anti-inflammation and regulating energy metabolism. In order to investigate the effects of sea buckthorn powder and sea buckthorn flavonoids on the antioxidant properties, immune function, and muscle fatty acid composition of common carp, an oral feeding experiment was carried out. The administration of glucose significantly reduced the levels of GSH and the activity of T-AOC enzyme in serum and hepatopancreas, while concurrently up-regulating the level of MDA (P < 0.05). Conversely, oral intake of sea buckthorn powder and flavonoids increased antioxidant enzyme activity and decreased MDA levels. In terms of antioxidant molecular indicators, sea buckthorn powder and sea buckthorn flavonoids significantly increased the mRNA levels of nuclear factor NF-E2-related factor (nrf2) in the hepatopancreas and muscle. Meanwhile, mRNA expression levels of downstream antioxidant-related genes (gr, cat, gpx, and sod) regulated by Nrf2 were also up-regulated. In the immune aspects, the mRNA expression levels of the pro-inflammatory cytokines, such as interleukin-6 (il-6), interleukin-1β (il-1β) and nuclear factor-κB (nf-κb) were reduced, but the expressions of anti-inflammatory cytokines, such as growth factor-β (tgf-β) and interleukin-10 (il-10) were enhanced in the head kidney and spleen tissues after oral administration with sea buckthorn. In terms of muscle fatty acid composition, the ratio of n-3 PUFA/n-6 PUFA was notably higher after administering sea buckthorn flavonoids than that of the glucose group (P < 0.05). This study demonstrated that oral administration of sea buckthorn powder and sea buckthorn flavonoids significantly enhanced the antioxidant capacity and immune response, improved the muscle fatty acid compositions in common carp, and also mitigated the adverse effects of glucose treatment to a certain extent. This article is protected by copyright. All rights reserved.

Effect of Salicylic Acid Treatment on Disease Resistance to Coleosporium zanthoxyli in Chinese Pepper (Zanthoxylum armatum).

The fungus Coleosporium zanthoxyli causes leaf rust in Chinese pepper (Zanthoxylum armatum). To investigate the control effect of elicitor treatment on leaf rust in this species, the impact of salicylic acid (SA) on the spores and growth of C. zanthoxyli and the induced resistance to leaf rust by Z. armatum were analyzed, and the possible defense mechanisms involved in SA induction were evaluated. The results showed that SA had no effect on C. zanthoxyli spore germination and growth; however, rust resistance was induced in Z. armatum. The optimal SA treatment concentration was 0.4 mg/ml, and the relative cure effect reached 44.56%. SA-induced disease resistance was evident for up to 10 days, while the optimal induction interval was 48 h after stimulation. Consistent with the induced resistance, H2O2, total protein, total phenol, and lignin concentrations and polyphenol oxidase (PPO), peroxidase (POD), phenylalanine ammonia lyase (PAL), superoxide dismutase (SOD), and catalase (CAT) activities were significantly increased with the SA treatment, whereas the malondialdehyde content was significantly decreased. In addition, exogenous SA promoted defense-related enzyme activities, including those of POD, CAT, and PAL, and increased H2O2, lignin, and endogenous SA contents. Furthermore, SA induced the expression of SA signaling pathway genes such as ZaPR1 and ZaNPR1, and silencing ZaPR1 enhanced the sensitivity of Z. armatum to leaf rust. Our results demonstrated that 0.4 mg/ml SA priming increased the activities of CAT, POD, and PAL, elevated the contents of H2O2, lignin, and endogenous SA, and upregulated the expression of the SA-related gene ZaPR1, thereby enhancing the resistance of Z. armatum to leaf rust.

Caffeine Adsorption on a Thermally Modified Bentonite: Adsorbent Characterization, Experimental Design, Equilibrium and Kinetics

Caffeine is a chemical compound found in various products such as coffee, tea, and energy drinks; therefore, it is common in wastewater and surface water. The present study investigated caffeine adsorption on a thermally modified bentonite-type clay. The effects of the heat treatment of the adsorbent over the temperature range of 60–500 °C, as well as the initial pH of the solution, stirring speed, and contact time, on the removal of caffeine were analyzed. The adsorbent was characterized by XRF, XRD, FT–IR, thermal analysis (TGA–DSC), and N2 physisorption at 77 K. The response surface methodology (RSM) based on a central composite design (CCD) was used to evaluate and optimize the adsorption of caffeine in aqueous solution. The maximum adsorption capacity of caffeine obtained with the Langmuir model was 80.3 ± 2.1 mg/g (0.41 ± 0.01 mmol/g) at 25 °C under equilibrium conditions (initial pH = 8.0, stirring speed = 400 rpm, contact time = 120 min). A kinetic study showed that the pseudo-second-order and Elovich models adequately describe the adsorption process. Bentonite thermally modified at 400 °C can be considered a low-cost adsorbent with potential application for removing caffeine in aqueous media.

Management of enamel demineralization- An iatrogenic effect of orthodontic treatment: A case report

Areas of demineralised enamel, usually referred to as white spot lesions (WSLs), constitute to a clinical problem in Orthodontics following treatment with fixed appliances. They result due to an imbalance between de- and remineralisation of enamel, caused by the inter-relationship of several factors. This manuscript is intended to elucidate the presentation of a clinical case treated with orthodontic braces with 10-year follow up, and management of demineralization with veneers that occurred due to long term fixed orthodontic treatment. The goal of treatment has been achieved according to patient’s desire and satisfactory digital veneer placement. No further relapse has been seen in the follow up. The treatment resulted in an aesthetic, functional, and stable occlusion, along with improved facial profile.

Resveratrol relieves HFD-induced insulin resistance in skeletal muscle tissue through antioxidant capacity enhancement and the Nrf2-Keap1 signaling pathway.

Resveratrol has received much attention due to its beneficial effects including antioxidant activity. The purpose of this study was to investigate the therapeutic effects of resveratrol treatment on oxidative stress and insulin resistance in the skeletal muscle of high-fat diet (HFD)-fed animals. A total of 30 six-week-old C57BL/6J mice were randomly allocated to three groups (10 animals in each group): The control group in which mice were fed a normal chow diet (NCD); the HFD group in which mice were fed an HFD for 26 weeks; and the HFD-resveratrol group in which HFD was replaced by a resveratrol supplemented-HFD (400mg/kg diet) after 10 weeks of HFD feeding. At the end of this period, gastrocnemius muscle samples were examined to determine insulin resistance and the oxidative status in the presence of HFD and resveratrol. Resveratrol supplementation in HFD-fed mice reduced body and adipose tissue weight, improved insulin sensitivity, and decreased oxidative stress as indicated by lower malonaldehyde (MDA) levels and higher total antioxidant capacity. The supplement also increased the expression and activity of antioxidative enzymes in gastrocnemius muscle and modulated Nrf2 and Keap1 expression levels. These results suggest that resveratrol is effective in improving the antioxidant defense system of the skeletal muscle in HFD-fed mice, indicating its therapeutic potential to combat diseases associated with insulin resistance and oxidative stress.

Effect of ethanol extract of nigella sativa L seeds and propofol on BDNF protein level as neuroplasticity and neuroprotection of traumatic brain injury in rats

Background Traumatic brain injury (TBI) is a change in brain function or evidence of brain pathology caused by external mechanical forces. Brain Derived Neurotrophic Factor (BDNF) is a neurotropin that functions as a neuron protective. Nigella sativa L is reported to have an antioxidant effect, administration of Nigella Sativa L to rats treated with ischemia-reperfusion brain injury. Propofol is an anesthetic agent frequently used intravenously in the management of TBI. The effect of propofol on brain tissue after TBI may be neuroprotective. We aimed to compare the potential of Nigella sativa L and propofol as neuroplasticity and neuroprotection in rats with TBI. Methods This was a laboratory experimental animal model with the post-test only control group design, namely measuring the effect of treatment by comparing the five groups of rats consisting of 30 rats. BDNF levels in rat brain tissue were collected at day 7 of treatment and measured by ELISA. Results The average BDNF protein levels per group, namely G1 (221,243 pg/mL), G2 (172,139 pg/mL), G3 (255,483 pg/mL), G4 (227,089 pg/mL), and G5 (272,603 pg/mL) respectively. Based on the ANOVA statistic, p-value = 0.032 (there was a significant difference between groups), with the Levene Test (0.077) or having variance between the same groups, sequentially the difference in average BDNF protein levels of the five groups is G5&gt;G3&gt;G4&gt;G1&gt;G2, meaning that the combination of Nigella sativa and propofol has more potential to increase BDNF protein levels than Nigella sativa, and Nigella sativa has more potential than propofol. Conclusion We concluded that both nigella sativa and propofol have the potential to increase BDNF protein levels. Nigella Sativa L had a better effect than propofol in repairing damaged neuron cells (neuroplasticity) and increasing BDNF protein levels (neuroprotection) for 7 days of administration in rat traumatic brain injury.

The application of propensity score methods in observational studies

IntroductionIn research, it is crucial to accurately estimate treatment effects and analyze experimental results. Common methods include comparing outcome differences between different groups and using linear regression models for analysis. However, observational studies may have significantly different distributions of confounding variables between control and treatment groups, leading to errors in estimating treatment effects.MethodsThe propensity score methods can address this issue by weighting or matching samples to approximate the scenario of a randomized experiment and allow for more accurate estimation of treatment this paper.ResultsWe use propensity score methods to analyze three datasets from observational studies and draw conclusions different from those in the original text. Furthermore, we simulate three scenarios, and the results demonstrate the superiority of propensity score methods over methods such as linear regression in addressing selection bias.DiscussionTherefore, it is essential to thoroughly consider the characteristics of the data and select appropriate methods to ensure reliable conclusions in practical data analysis.

Early Metabolic Endpoints Identify Persistent Treatment Efficacy in Recent-Onset Type 1 Diabetes Immunotherapy Trials.

Mixed-meal tolerance test-stimulated area under the curve (AUC) C-peptide at 12-24 months represents the primary end point for nearly all intervention trials seeking to preserve β-cell function in recent-onset type 1 diabetes. We hypothesized that participant benefit might be detected earlier and predict outcomes at 12 months posttherapy. Such findings would support shorter trials to establish initial efficacy. We examined data from six Type 1 Diabetes TrialNet immunotherapy randomized controlled trials in a post hoc analysis and included additional stimulated metabolic indices beyond C-peptide AUC. We partitioned the analysis into successful and unsuccessful trials and analyzed the data both in the aggregate as well as individually for each trial. Among trials meeting their primary end point, we identified a treatment effect at 3 and 6 months when using C-peptide AUC (P = 0.030 and P < 0.001, respectively) as a dynamic measure (i.e., change from baseline). Importantly, no such difference was seen in the unsuccessful trials. The use of C-peptide AUC as a 6-month dynamic measure not only detected treatment efficacy but also suggested long-term C-peptide preservation (R2 for 12-month C-peptide AUC adjusted for age and baseline value was 0.80, P < 0.001), and this finding supported the concept of smaller trial sizes down to 54 participants. Early dynamic measures can identify a treatment effect among successful immune therapies in type 1 diabetes trials with good long-term prediction and practical sample size over a 6-month period. While external validation of these findings is required, strong rationale and data exist in support of shortening early-phase clinical trials.

Improving Inverse Probability Weighting by Post-calibrating Its Propensity Scores.

Theoretical guarantees for causal inference using propensity scores are partially based on the scores behaving like conditional probabilities. However, scores between zero and one do not necessarily behave like probabilities, especially when output by flexible statistical estimators. We perform a simulation study to assess the error in estimating the average treatment effect before and after applying a simple and well-established postprocessing method to calibrate the propensity scores. We observe that postcalibration reduces the error in effect estimation and that larger improvements in calibration result in larger improvements in effect estimation. Specifically, we find that expressive tree-based estimators, which are often less calibrated than logistic regression-based models initially, tend to show larger improvements relative to logistic regression-based models. Given the improvement in effect estimation and that postcalibration is computationally cheap, we recommend its adoption when modeling propensity scores with expressive models.