Acid Exposure Research Articles

Concurrent abnormal non-acid reflux is associated with additional chronic rejection risk in lung transplant patients with increased acid exposure.

Acid reflux has been associated with allograft injury and rejection in lung transplant patients; however, the pathogenic role of non-acid reflux remains debated. We aimed to evaluate the impact of concurrent abnormal non-acid reflux with acid reflux on chronic rejection in lung transplant patients with acid reflux. This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant combined impedance-pH study off acid suppression. Only subjects with acid exposure >4% were included. Non-acid reflux (pH > 4) episodes >27 was considered abnormal per prior normative studies. Chronic rejection was defined as chronic lung allograft dysfunction (CLAD) per International Society for Heart and Lung Transplantation criteria. Time-to-event analyses were performed using Cox proportional hazards and Kaplan-Maier methods, with censoring at death, anti-reflux surgery, or last follow-up. In total, 68 subjects (28 abnormal/40 normal non-acid reflux) met inclusion criteria for the study. Baseline demographic/clinical characteristics were similar between groups. Among this cohort of patients with increased acid exposure, subjects with concurrent abnormal non-acid reflux had significantly higher risk of CLAD than those without on Kaplan-Meier analysis (log-ranked P = 0.0269). On Cox multivariable regression analysis controlling for body mass index, age at transplantation, and proton pump inhibitor use, concurrent abnormal non-acid reflux remained independently predictive of increased CLAD risk (hazard ratio 2.31, confidence interval: 1.03-5.19, P = 0.04). Presence of concurrent abnormal non-acid reflux in lung transplant subjects with increased acid exposure is associated with additional risk of chronic rejection. Non-acid reflux may also contribute to pathogenicity in lung allograft injury/rejection, supporting a potential role for impedance-based testing in this population.

Abstract 4295: Apoptotic DNase DFFB-induced DNA damage within cancer persister cells underlies acquired resistance to targeted therapies across multiple tumor types

Abstract Cancer acquired drug resistance contributes to a large proportion of patient deaths. A major obstacle to the development of effective therapies which prevent resistance is our lack of understanding of the relevant fundamental molecular adaptive processes. Here we report the discovery that tumor cells rely upon sublethal engagement of apoptotic death machinery and apoptotic DNase DFFB to acquire resistance to targeted therapies in multiple tumor types in cell culture and in vivo. We found that while DFFB wild type tumor cells readily acquire resistance to targeted therapies by escaping from the quiescent “persister” state into proliferating resistant cells, persister cells lacking functional DFFB remain indefinitely in a quiescent state on treatment. Mechanistically, we found that DFFB, which is activated by apoptotic caspases in surviving cancer persister cells, induces persistent DNA damage which promotes resistance through acquired mutations and nongenetic resistance through suppression of growth-arresting interferon signaling. During drug treatment acute interferon induction arises from sublethal mitochondrial outer membrane permeabilization and cytoplasmic exposure of mitochondrial nucleic acids which activate pattern recognition receptors. However, during longer treatments we found that DFFB knockout persister cells exhibit strikingly elevated levels of STAT1 and STAT2 and interferon stimulated gene sets. This interferon signaling is growth arresting because treatment of DFFB knockout persister cells with a JAK1/2 inhibitor rescues their ability to regrow. Furthermore, in DFFB wild type persister cells we found that DFFB-dependent DNA damage activates stress response transcription factor ATF3 which blocks the transcriptional activation of interferon stimulated genes following initial interferon induction. This is consistent with prior data in other contexts demonstrating that ATF3 is induced by DNA damage and that ATF3 directly binds to promoters of multiple interferon genes repressing their expression. These findings reveal that DFFB activation in persister cells prevents chronic interferon signaling and enables escape into proliferating drug resistant tumor cells. Therefore, DFFB-mediated interferon suppression represents a novel mechanism that is fundamental to acquired drug resistance. In addition, high expression of DFFB and ATF3 correlates with worse overall survival in a pan-cancer analysis and DFFB knockout mice develop normally indicating DFFB is a nonessential gene in normal tissue. Therefore, we propose that DFFB is a promising therapeutic target to prevent acquired resistance to targeted therapy. Citation Format: August Finley Williams, David A. Gervasio, Claire E. Turkal, Anna E. Stuhlfire, Michael X. Wang, Brandon E. Mauch, Ariel H. Nguyen, Michelle H. Paw, Mehrshad Hairani, Cooper P. Lathrop, Sophie H. Harris, Jennifer L. Page, Matthew J. Hangauer. Apoptotic DNase DFFB-induced DNA damage within cancer persister cells underlies acquired resistance to targeted therapies across multiple tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4295.

Abstract 3269: APE1/NF-κB/PRDX2 activated by reflux conditions mediates chemoresistance in esophageal adenocarcinoma by suppressing ferroptosis

Abstract Background: Esophageal adenocarcinoma (EAC) stands out as one of the most lethal malignancies, characterized by a discouragingly low 5-year survival rate of less than 20%. Accumulating lines of evidence indicate that ferroptosis, a novel type of cell death, can regulate drug resistance. Peroxiredoxin 2 (PRDX2), an antioxidant enzyme, plays an antioxidant protective role in the cells under stress by regulating redox homeostasis. We aimed to elucidate the role of PRDX2 in regulating reactive oxygen species (ROS), ferroptosis, and chemoresistance in EAC. Methods: In this investigation, we analyzed RNA sequencing data and public databases to uncover the aberrant overexpression and potential chemoresistance function of PRDX2 in EAC. We employed transient acidic bile salts exposure (ABS) and repeated ABS exposure (rABS) to mimic gastroesophageal reflux disease, the main risk factor for EAC, in in vitro cell models. EAC cells and 3D organotypic culture (OTC) served as platforms to delve into the anti-ferroptosis function and regulatory mechanisms of PRDX2. The findings were validated using patient-derived xenografts (PDX) and human EAC tissue microarrays (TMA). Results: Elevated PRDX2 level was observed in both EAC patients and cell lines exhibiting poor responsiveness to chemotherapy. Intrinsic overexpression of PRDX2 emerged as a crucial factor in the recovery from ABS-exposure-induced lipid peroxidation. Silencing PRDX2 heightened the sensitivity of EAC cells to Oxaliplatin by inhibiting ferroptosis in a GPX4-dependent manner. Mechanistically, we found ABS activate the APE1/redox/NF-kB signal axis, leading to the upregulation of PRDX2 transcription. The co-overexpression of APE1 and PRDX2 was identified through both immunofluorescent staining in cells/OTC and immunohistochemistry staining in TMA. Moreover, the APE1-redox-specific inhibitor, APX2009, significantly sensitized EAC cells to Oxaliplatin by repressing PRDX2 and inducing ferroptosis. Remarkably, the combination therapy of Oxaliplatin and APX2009 achieved a synergistic effect in EAC-PDX tumors. Conclusion: The study unveils a novel signaling axis, APE1/NF-kB/PRDX2, linking disease-associated ROS unbalance and ferroptosis-related chemoresistance. Targeting PRDX2 signaling by APE1-redox-specific inhibition provides a potential novel strategy for combined chemotherapies in refractory EAC. Citation Format: Lei Chen, Heng Lu, Farah Ballout, Dunfa Peng, Zheng Chen, Jianwen Que, Steven Chen, Oliver McDonald, Alexander Zaika, Wael El-Rifai. APE1/NF-κB/PRDX2 activated by reflux conditions mediates chemoresistance in esophageal adenocarcinoma by suppressing ferroptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3269.

Abstract 6160: Mutational signatures and their associations with social determinants of health

Abstract Introduction: Mutational signatures, or unique patterns of genetic mutations due to exogenous and endogenous mutational processes, are being continuously identified through the analysis of cancer patients’ genomes. While cancer research has developed and mortality rates have declined, disparities in cancer outcomes have widened. Social determinants of health (SDOH), such as access to health care, education, and economic stability are essential to addressing health equity. While much research is ongoing regarding the identification and etiology of mutational signatures, little work has been published regarding the associations of these signatures with SDOH. Therefore, this study proposes an exploration into the relationships between the presence of mutational signatures and SDOH within an adult pan-cancer patient population. Methods: Variant calls from whole exome sequencing for each patient was used to infer the presence of 58 single base substitution (SBS) mutational signatures. Descriptive statistics were calculated for 455 unique patients. Previously documented associations between primary diagnosis site and distinct signatures were used to validate the predicted signatures in the patient population. Signature profiles were then linked to 208 patient health records with complete SDOH. Logistic regression predicting the presence of each signature was modeled for these patients. Full models for each signature included age, gender, Rural-Urban Commuting Area (RUCA) code, tobacco and alcohol usage, education, income, housing condition, and access to healthcare. Stepwise selection was used to determine significant variables. Results: The most common signatures in the complete population (n = 455) were SBS1 (clock-like; 98%) and SBS39 (95%), followed by SBS5 (clock-like; 38%) and SBS22 (aristolochic acid exposure; 36%). However, SBS24 (aflatoxin exposure; p = .019) and SBS7a (UV exposure; p = .002) were significantly more common in lung and skin cancer patients respectively. Each patient had 4.1 signatures on average, with a range of 2-7. The average number of signatures per patient varied significantly by primary diagnosis (ANOVA p = .014). Patients with a vulva/vagina (4.8) or bladder/urinary tract (4.9) diagnosis had the highest number of signatures while those with a liver (3.3) or kidney (3.6) diagnosis had the lowest. Logistic regression models for the population with SDOH (n = 208) showed poor housing condition was associated with SBS4 (tobacco smoking; p = 0.091). Any issue in accessing healthcare was associated with SBS13 (AID/APOBEC; p = 0.114) and SBS21 (MMR; p = 0.076). Greater rurality was associated with SBS16 (p = .144) and SBS21 (p = .107). The relationship was inverse for SBS1 (p = .121). Conclusion: Multiple significant relationships between different SDOH and mutational signatures was revealed, pointing the need to extend this research to larger patient populations with diverse SDOH. Citation Format: Padmapriya Swaminathan, McKenna Deaton, Crystal Hattum, Benjamin Solomon, William Spanos, David Starks, Rachel Elsey, Casey Williams, Tobias Meissner. Mutational signatures and their associations with social determinants of health [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6160.

Abstract 3069: Targeting lactic acid sensing GPR132 in ccRCC

Abstract Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype of kidney cancer, accounting for 70-80% of the cases. Despite the improvements in tumor therapeutics, patients with metastatic clear cell tumors still have a five-year survival rate lower than 10%. Most of the ccRCC tumors harbor loss of VHL tumor suppressor gene on chromosome 3, leading to constitutively stabilized HIF, activation of downstream pathways involved in glycolysis, angiogenesis and metastasis and a highly acidic, vascularized, and immunosuppressive tumor microenvironment (TME). Such molecular alterations lead to the buildup of lactic acid within the tumor microenvironment. Long has been considered as a byproduct of hypoxic tumor metabolism, but recent studies have demonstrated a pro-tumorigenic role of lactic acid. Therefore, elucidating the molecular mechanisms on how tumor cells take advantage of lactic acid can identify potential novel therapeutic options. To understand how ccRCC cells sense extracellular lactic acid, I explored the concept of a lactate sensor. The currently known lactate sensors are GPR81 and GPR132. By querying TCGA data, GPR81 is reduced in ccRCC tumors and does not predict patient outcome while GPR132 is elevated in ccRCC tumors compared to normal kidney and demonstrates a strong negative effect on survival. Therefore, GPR132 stands out as a potential lactate sensor in ccRCC with meaningful impact on patient survival. Previously, GPR132 has been shown to be involved in tumor associated macrophage M1 to M2 transition upon lactic acid exposure. However, GPR132 exerts a striking impact on ccRCC tumors. Depleting GPR132 significantly decreased the HIF2α level in multiple ccRCC cell lines, establishing a molecular connection between lactic acid, GPR132 and HIF2α. Furthermore, due to suppressed HIF2α signaling, GPR132 knockout led to decreased lactic acid uptake through MCT1. Such decreased lactic transporter MCT1 abrogated the elevated aggressive phenotype in ccRCC cells when exposed to lactic acid. Metabolically, GPR132 knockout led to decreased lipid deposition. In addition, such deprivation of lipid droplet is not replenished when cells are exposed to lactic acid. Furthermore, by conducting an isotype-tracing experiment, GPR132 knockout actively decreased lactic acid uptake by the tumors and limit their resources to regenerate TCA cycle intermediates and build up lipid droplets. More importantly, GPR132 knockout led to defective mitochondria activities and activation of apoptosis, both of which led to significantly suppressed ccRCC growth in vitro and in vivo. This suggested that GPR132 likely affects ccRCC fitness through multiple layers of signaling mechanisms. Overall, our study has revealed that lactate sensing GPR132 is a critical signaling pathway for ccRCC tumor development in a glycolytic feed-forward context. As a membrane bound receptor, GPR132 holds immense potential as a novel therapeutic target in ccRCC. Citation Format: Dazhi Wang. Targeting lactic acid sensing GPR132 in ccRCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3069.

Abstract 1478: Chronic perfluorooctanesulfonic acid exposure promotes proliferation of colorectal cancer cells

Abstract Background: Chronic exposure to long-term exposures to per- and polyfluoroalkyl substances (PFAS), widely known as “forever chemicals”, has been associated with multiple negative health outcomes including increased risk of cancer. Perfluorooctanesulfonic acid (PFOS), a “long-chain” subtype of PFAS, has high bioaccumulation potential with a long elimination half-life. PFOS is frequently detected in drinking water leading to its high absorption through the gastrointestinal tract. Recent studies demonstrate that PFAS exposures promote intestinal inflammation and gut barrier dysfunction. However, how a long-term PFOS exposure affects colorectal cancer (CRC) progression is not known. Therefore, the purpose of this study is to delineate the effect of PFOS exposure on CRC cell proliferation and test the potential mitigation strategy for the harmful effects of PFOS. Methods: SW480 and HCT116 cells have been treated with 1 ug/mL PFOS and proliferation was measured at 1, 2, and 3 months using the Presto Blue Cell Viability Reagent fluorescence assay. Proliferation markers were assessed by qPCR and Western blot. Control and PFOS exposed cells were treated with sulforaphane, a nuclear factor erythroid 2-related factor 2 (Nrf-2) inducer, at concentration 5, 10 and 20 uM for 72 hours. Results: We show that chronic, low-dose PFOS exposure promotes proliferation of SW480 and HCT116 cell lines starting at 3 months since the first exposure. The increase in proliferation is associated with upregulation of Cyclin D, pAkt and FASN. We also show that sulforaphane significantly decreases proliferation of HCT116 and SW480 cells, and its efficacy is significantly higher in PFOS exposed CRC cells. The current studies show no effect on sulforaphane on normal colon epithelium cells. Conclusion: Our studies suggest that chronic PFOS exposure promotes proliferation of CRC cells by increasing pro-carcinogenic gene expression and signaling. Furthermore, our findings suggest that supplementation of diet sulforaphane can potentially mitigate the harmful effects from PFOS exposure. Our studies warrant further investigation of the mechanisms behind the effect of PFOS exposure on cancer progression that would guide development of effective intervention strategies to mitigate the harmful effects of the exposure to “forever chemicals”. Citation Format: Jerika Durham, Josiane Weber Tessmann, Bernhard Hennig, Yekaterina Zaytseva. Chronic perfluorooctanesulfonic acid exposure promotes proliferation of colorectal cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1478.

Abstract 1480: Perfluorooctanesulfonic acid exposure promotes pathological changes in normal intestinal tissues which may lead to an increased risk of colorectal cancer development

Abstract Introduction: Long-term exposures to per- and polyfluoroalkyl substances (PFAS) have been increasingly linked to negative health outcomes including metabolic disorders, reduced immune responses, and increased risk of cancer. PFOS, one the most frequently detected PFAS in drinking water, is readily absorbed in the GI tract and distributes predominantly to the plasma and liver. Even though recent studies demonstrate that PFOS can cause an imbalance of cecal gut microbiota, alter microbiota diversity, and promote inflammation and gut barrier dysfunction, there is still not much known about the effects of PFOS exposure on normal and pre-malignant intestinal tissues and its contribution to carcinogenesis. Therefore, the goal of this study is to investigate the effects of PFOS on normal (I) and malignant intestinal cells (II). Methods: The effect of PFOS on gene expression profile was assessed by RNAseq analysis in intestinal tissue of C57BL/6 mice. Tumor organoids were established from Apc/VillinCre mice (adenoma models). Organoid cultures, colorectal cancer (CRC) and primary normal intestinal cell lines have been treated with 1μg/ml of PFOS. To access the mechanisms involved in PFOS-induced intestinal alterations, qRT-PCR, western blot, immunofluorescence, cytokine array and metabolomics analysis have been performed. Results: The RNAseq analysis showed that PFOS exposure is associated with transcriptome alterations with exacerbated changes in pathways involved in lipid metabolism, immune system regulation and pro-carcinogenesis signaling. PFOS exposure leads to a significant decrease in expression of 3-hydroxy-3-methylglutaryl-Coa synthase 2 (HMGCS2), a rate limiting ketogenic enzyme, in intestinal tissues. We also showed that PFOS exposure upregulates fatty acid synthase, a key enzyme of de novo lipogenesis, programmed death-ligand, an immune checkpoint inhibitor, and altered the levels of pro-inflammatory cytokines and metabolites. Using HMGCS2 knockout cells, we identified the possible contribution of HMGCS2 in cytokine regulation and activation of oncogenic pathways. Conclusion: In summary, our data suggests that PFOS may induce gastrointestinal pathological changes that can increase the risk of CRC development. Further studies are warranted to determine the functional significance of PFOS-mediated downregulation of HMGCS2 and upregulation of lipid metabolism in intestinal cells. Delineating the effects of PFOS on intestinal epithelium may contribute to development of interventional strategies to eliminate harmful effects of these environmental pollutants. Citation Format: Josiane Weber Tessmann, Jerika Durham, Ryan Goettl, Dang he, Chi Wang, Pan Deng, Bernhard Hennig, Yekaterina Zaytseva. Perfluorooctanesulfonic acid exposure promotes pathological changes in normal intestinal tissues which may lead to an increased risk of colorectal cancer development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1480.

Current Status of Anti-Reflux Surgery as a Treatment for GERD.

Anti-reflux surgery (ARS) is an efficient treatment option for gastroesophageal reflux disease (GERD). Despite growing evidence of the efficacy and safety of ARS, medications including proton pump inhibitors (PPIs) remain the most commonly administered treatments for GERD. Meanwhile, ARS can be an effective treatment option for patients who need medications continuously or for those who are refractory to PPI treatment, if proper candidates are selected. However, in practice, ARS is often regarded as a last resort for patients who are unresponsive to PPIs. Accumulating ARS-related studies indicate that surgery is equivalent to or better than medical treatment for controlling typical and atypical GERD symptoms. Furthermore, because of overall reduced medication expenses, ARS may be more cost-effective than PPI. Patients are selected for ARS based on endoscopic findings, esophageal acid exposure time, and PPI responsiveness. Although there is limited evidence, ARS may be expanded to include patients with normal acid exposure, such as those with reflux hypersensitivity. Additionally, other factors such as age, body mass index, and comorbidities are known to affect ARS outcomes; and such factors should be considered. Nissen fundoplication or partial fundoplication including Dor fundoplication and Toupet fundoplication can be chosen, depending on whether the patient prioritizes symptom improvement or minimizing postoperative symptoms such as dysphagia. Furthermore, efforts to reduce and manage postoperative complications and create awareness of the long-term efficacy and safety of the ARS are recommended, as well as adequate training programs for new surgeons.

Evaluating acidic gastroesophageal reflux with wireless pH monitoring in French bulldogs with sliding hiatal herniation.

Sliding hiatal herniation (SHH) and gastroesophageal reflux (GER) commonly occur in French bulldogs. Wireless pH monitoring can quantitatively assess acidic GER in dogs affected by SHH. Measure acidic GER in French bulldogs with SHH, pre- and post-brachycephalic obstructive airway syndrome (BOAS) surgery, utilizing a wireless pH capsule (Bravo Calibration-free, Medtronic, Minnesota), and correlate with owners' observations of regurgitation. Eleven French bulldogs diagnosed with SHH via swallowing fluoroscopy. Prospective cohort study. A pH capsule was endoscopically placed in the esophagus. Up to 96 hours of data were acquired as the owner logged clinical signs. Spearman's correlation and Wilcoxon rank-sum tests evaluated factors correlated with acid exposure time (AET), defined by the % time pH < 4. In 4/11 dogs, Bravo monitoring was repeated 2-4 months after BOAS surgery. Medians (Q1-Q3) for age and weight were 21 months (17-35.5) and 10.0 kg (8.9-11.5). BOAS severity was mild (3), moderate (4), or severe (4). Medians (Q1-Q3) for AET and reflux events were 3.3% (2.6-6.4) and 70 (34-173). Clinical score (P = .82) and BOAS severity (P = .60) were not correlated with AET, but age was negatively correlated (rho = -.66, P = .03). Median probability (Q1-Q3) that regurgitation was associated with a reflux event was 72.5% (0-99). Percent AET numerically improved in all 4 dogs that underwent BOAS surgery although not statistically assessed. Wireless pH monitoring documented acidic GER in French bulldogs with SHH, captured subclinical events, and showed improvements after BOAS surgery.

Insight of Cadmium Solidification by Mineral‐Based Soil Conditioner

AbstractIn response to the environmental concerns posed by cadmium (Cd) contamination, the application of nano‐submicron mineral‐based soil conditioner (MSC) as a potential soil amendment has garnered interest due to its promising Cd mitigation properties. In this study, we aimed to investigate the solidification capacity and mechanism of Cd in MSC and examine the phase and morphology changes following solidification. Systematic experiments were conducted to assess the solidification capacity of MSC for Cd, revealing an impressive efficiency of nearly 100 % even at Cd concentrations of approximately 800 mg/L. The solidification efficiency was found to be positively correlated with the pH value, significantly declining as the environment shifted from pH&gt;7 to pH&lt;7. Notably, under alkaline conditions (pH&gt;7), Cd solidification in MSC was primarily attributed to the Cd‐OH complex formed on the surface of MSC and aided by cation‐exchange reaction. In contrast, under acidic conditions (pH&lt;7) and exposure to extreme Cd concentrations, Cd(OH)Cl precipitation became the dominant mechanism for solidification. Interestingly, the presence of KCdCl3, a water‐soluble phase, did not significantly contribute to the overall solidification efficiency. These findings provide valuable insights into the solidification mechanism of Cd in MSC and offer potential implications for soil remediation efforts targeting Cd contamination.

Analysis of Effect of Acid &amp; Alkali on the Strength of Concrete with Fly Ash

This study investigates the impact of curing concrete in both acidic and alkaline water on its strength. Through comprehensive testing, the research aims to provide insights into how varying curing environments influence the structural integrity of concrete, offering valuable information for construction practices and durability considerations. The findings aim to enhance our understanding of concrete behaviour in diverse curing environments, contributing to the optimization of construction practices in varying water quality scenarios. Now a days the effect on acid and base exposure on strength and durability of concrete through experimentation. Concrete cubes mix will be prepared and exposed to different concentration and Diluted solution of H2So4 and NaoH. For 7 &amp; 28 days. Total of 18 cubes of Size 150mm×150mm×150mm are cast with M-20,M-30 &amp;M-35 grades of Concrete cubes are cured in normal or acid, alkali solution for 7 and 28 days. The cured cubes are then tested for compressive testing machine to determine their compressive strength.

Prolonged acid reflux monitoring using acid exposure time and DeMeester score: two days are not enough.

Wireless pH monitoring allows for a definitive GERD diagnosis, which is essential for optimal medical or surgical management of the patient. However, there is no guideline recommendation on whether prolonged pH testing (72 or 96h) provides additional benefit when compared to the standard 48-h testing. We aimed to assess whether prolonged pH monitoring diagnoses more patients with GERD, as well as compare the DeMeester score to acid exposure time as diagnostic criteria for GERD. This was a retrospective analysis of consecutive adult patients who underwent wireless esophageal pH monitoring between August 2018 and July 2021. The primary outcome was the additional diagnoses of GERD (predominant acid exposure pattern) in patients who underwent 48-h versus 96-h pH monitoring. Secondary outcomes included comparison of the DeMeester score to acid exposure time and internal agreement between the first and second 48-h blocks of a prolonged96-hpH study. When comparing 48-h versus 96-h pH testing, the prolonged monitoring group was more likely to have a predominant reflux pattern and thus be diagnosed with definitive GERD by elevated DeMeester score (58.8% vs. 40.8%, p = 0.003) or acid exposure time > 6% (44.7% vs. 32.4%, p = 0.039). For patients who underwent prolonged testing, the results of monitoring beyond 48h led to a clinically meaningful change in study interpretation in 24.8% of patients. The study data from Days 3 to 4 yielded only a 56.6% agreement with the first 2days. In patients undergoing extended pH monitoring, almost half were found to have an abnormal pH study after a normal study on Day 1. An additional 25% of patients had a change in study interpretation by extending the study beyond 48h. Our findings suggest only 48h of pH monitoring will miss a diagnosis of GERD in a clinically important number of patients.

Efficacy and safety of endoscopic cardia peripheral tissue scar formation (ECSF) for the treatment of refractory gastroesophageal reflux disease: A systematic review with meta-analysis.

Endoscopic treatment is increasingly used for refractory gastroesophageal reflux disease (rGERD). Unlike the mechanism of conventional surgical fundoplication, gastroesophageal junction ligation, anti-reflux mucosal intervention, and radiofrequency ablation have extremely similar anti-reflux mechanisms; hence, we collectively refer to them as endoscopic cardia peripheral tissue scar formation (ECSF). We conducted a systematic review and meta-analysis to assess the safety and efficacy of ECSF in treating rGERD. We performed a comprehensive search of several databases, including PubMed, Embase, Medline, China Knowledge Network, and Wanfang, to ensure a systematic approach for data collection between January 2011 and July 2023. Forest plots were used to summarize and combine the GERD-health-related quality of life (HRQL), gastroesophageal reflux questionnaire score, and DeMeester scores, acid exposure time, lower esophageal sphincter pressure, esophagitis, proton pump inhibitors use, and patient satisfaction. This study comprised 37 studies, including 1732 patients. After ECSF, significant improvement in gastroesophageal reflux disease health-related quality of life score (mean difference [MD] = 18.27 95% CI: 14.81-21.74), gastroesophageal reflux questionnaire score (MD = 4.85 95% CI: 3.96-5.75), DeMeester score (MD = 42.34, 95% CI: 31.37-53.30), acid exposure time (MD = 7.98, 95% CI: 6.03-9.92), and lower esophageal sphincter pressure was observed (MD = -5.01, 95% CI: -8.39 to 1.62). The incidence of serious adverse effects after ECSF was 1.1% (95% CI: 0.9%-1.2%), and postoperatively, 67.4% (95% CI: 66.4%-68.2%) of patients could discontinue proton pump inhibitor-like drugs, and the treatment outcome was observed to be satisfactory in over 80% of the patients. Subgroup analyses of the various procedures showed that all 3 types improved several objective or subjective patient indicators. Based on the current meta-analysis, we conclude that rGERD can be safely and effectively treated with ECSF as an endoscopic procedure.

Prediction, prevention and management of gastroesophageal reflux after per-oral endoscopic myotomy: An update.

Achalasia cardia, the most prevalent primary esophageal motility disorder, is predominantly characterized by symptoms of dysphagia and regurgitation. The principal therapeutic approaches for achalasia encompass pneumatic dilatation (PD), Heller's myotomy, and the more recent per-oral endoscopic myotomy (POEM). POEM has been substantiated as a safe and efficacious modality for the management of achalasia. Although POEM demonstrates superior efficacy compared to PD and an efficacy parallel to Heller's myotomy, the incidence of gastroesophageal reflux disease (GERD) following POEM is notably higher than with the aforementioned techniques. While symptomatic reflux post-POEM is relatively infrequent, the significant occurrence of erosive esophagitis and heightened esophageal acid exposure necessitates vigilant monitoring to preclude long-term GERD-related complications. Contemporary advancements in the field have enhanced our comprehension of the risk factors, diagnostic methodologies, preventative strategies, and therapeutic management of GERD subsequent to POEM. This review focuses on the limitations inherent in the 24-h pH study for evaluating post-POEM reflux, potential modifications in the POEM technique to mitigate GERD risk, and the strategies for managing reflux following POEM.

Simulated gastric leachate of 3D printer metal-fill filaments induces cytotoxic effects in rat and human intestinal models

Metals are used in 3-dimensional (3D) printer filaments in the manufacture of 3D printed objects. Exposure to the filaments, printed objects and emissions from printing may pose health risks from release of toxic metals. This study investigated the cytotoxicity of extruded 3D printer filament leachates in rat and human intestinal cells. Copper-, bronze-, and steel-fill extruded filaments were incubated in acidic media for 2 h. Leachates were adjusted to pH 7 and cells exposed for 4 or 24 h. Concentration- and time-dependent decreases in rat and human cell viability were observed using a colorimetric assay and confirmed by microscopy. Copper- and bronze-fill leachates were more cytotoxic than steel. Copper-fill leachates had the highest copper concentrations by ICP-MS. Exposure to CuSO4 resulted in concentration-dependent cytotoxicity in rat cells. The copper chelator bathocuproine disulphonate alleviated cytotoxicity of CuSO4 and copper-fill leachate, suggesting that copper ions have a role in the cytotoxicity. Hydrogen peroxide increased and glutathione decreased in rat cells exposed to copper-fill leachate, suggesting the formation of reactive oxygen species. Overall, our data indicate that metals released from the acidic exposure of print objects using metal-fill filaments, especially copper, are toxic to rat and human intestinal cells and additional studies are needed.

Short and long term effect of anti-reflux mucosectomy with cap-assisted endoscopic mucosal resection for refractory gastroesophageal disease.

Anti-reflux mucosectomy with cap-assisted endoscopic mucosal resection (ARMS-C) is a safe and effective treatment for managing refractory gastroesophageal reflux disease (GERD). This study aimed to investigate the short and long-term outcomes of ARMS-C. This study was conducted from 2018 to 2022, during which 115 eligible patients underwent ARMS-C. The primary endpoints of this study were to evaluate the GERD-Q questionnaire score and determine the number of patients who reduced their proton pump inhibitor (PPI) dosage or discontinued PPI usage. The secondary endpoints included the evaluation of the DeMeester score, acid exposure time (AET), gastroesophageal flap valve grade (GEFV), lower esophageal sphincter pressure, the rate of successful esophageal peristalsis, and GERD-Q questionnaires. Additionally, we analyzed the long-term efficacy of ARMS-C. Out of the 120 patients, 115 underwent ARMS-C, 96 were followed up for at least six months after the procedure, and 22 were followed up for at least two years. The primary outcome showed a significant improvement in GERD-Q scores, decreasing from 10.67 to 7.55 (p < 0.001). Out of the 96 patients, 36 were able to reduce or completely stop using PPIs. The DeMeester score, GEFV, AET, and the proportion of intact peristalsis also demonstrated improvement. As for the long-term efficacy of ARMS-C, 86% of patients showed improvement in symptoms, and no serious adverse effects were reported after the procedure. ARMS-C is a safe and effective endoscopic technique to treat refractory GERD patients.

Association between exposure to a mixture of organochlorine pesticides and hyperuricemia in U.S. adults: A comparison of four statistical models

The association between the exposure of organochlorine pesticides (OCPs) and serum uric acid (UA) levels remained uncertain. In this study, to investigate the combined effects of OCP mixtures on hyperuricemia, we analyzed serum OCPs and UA levels in adults from the National Health and Nutrition Examination Survey (2005–2016). Four statistical models including weighted logistic regression, weighted quantile sum (WQS), quantile g-computation (QGC), and bayesian kernel machine regression (BKMR) were used to assess the relationship between mixed chemical exposures and hyperuricemia. Subgroup analyses were conducted to explore potential modifiers. Among 6,529 participants, the prevalence of hyperuricemia was 21.15%. Logistic regression revealed a significant association between both hexachlorobenzene (HCB) and trans-nonachlor and hyperuricemia in the fifth quintile (OR: 1.54, 95% CI: 1.08–2.19; OR: 1.58, 95% CI: 1.05–2.39, respectively), utilizing the first quintile as a reference. WQS and QGC analyses showed significant overall effects of OCPs on hyperuricemia, with an OR of 1.25 (95% CI: 1.09–1.44) and 1.20 (95% CI: 1.06–1.37), respectively. BKMR indicated a positive trend between mixed OCPs and hyperuricemia, with HCB having the largest weight in all three mixture analyses. Subgroup analyses revealed that females, individuals aged 50 years and above, and those with a low income were more vulnerable to mixed OCP exposure. These results highlight the urgent need to protect vulnerable populations from OCPs and to properly evaluate the health effects of multiple exposures on hyperuricemia using mutual validation approaches.

Prenatal PFAS exposure, gut microbiota dysbiosis, and neurobehavioral development in childhood

Studies on the role of the gut microbiota in the associations between per- and polyfluoroalkyl substance (PFAS) exposure and adverse neurodevelopment are limited. Umbilical cord serum and faeces samples were collected from children, and the Strengths and Difficulties Questionnaire (SDQ) was conducted. Generalized linear models, linear mixed-effects models, multivariate analysis by linear models and microbiome regression-based kernel association tests were used to evaluate the associations among PFAS exposure, the gut microbiota, and neurobehavioural development. Perfluorohexane sulfonic acid (PFHxS) exposure was associated with increased scores for conduct problems and externalizing problems, as well as altered gut microbiota alpha and beta diversity. PFHxS concentrations were associated with higher relative abundances of Enterococcus spp. but lower relative abundances of several short-chain fatty acid-producing genera (e.g., Ruminococcus gauvreauii group spp.). PFHxS exposure was also associated with increased oxidative phosphorylation. Alpha and beta diversity were found significantly associated with conduct problems and externalizing problems. Ruminococcus gauvreauii group spp. abundance was positively correlated with prosocial behavior scores. Increased alpha diversity played a mediating role in the associations of PFHxS exposure with conduct problems. Our results suggest that the gut microbiota might play an important role in PFAS neurotoxicity, which may have implications for PFAS control.

Performance of concrete superficially treated with nano-modified coatings under sulfuric acid exposures

Protection of concrete surface layer is crucial for preserving serviceability and durability of concrete structures during their service life. Chemical attack by sulfuric acid is an aggressive exposure, commonly causing significant damage to concrete elements such as buildings' foundations and basement walls, buildings and structures affected by acid rain, industrial facilities, and wastewater treatment facilities. Hence, this study endeavored to evaluate the performance of nano-modified composites as surface treatments for concrete under severe chemical exposures. Nano-calcium carbonate and nano-clay particles were dispersed at different dosages (0, 2.5, and 5% by mass) in the neat coatings: vinyl ester (membrane-forming polymer) and silane (hydrophobic agent). Moreover, an amorphous colloidal silica (SiO2>50%) was also used as a superficial treatment for concrete. These coatings were applied to concrete specimens with water-to-binder ratios (w/b) of 0.40 (representing good quality/low penetrability concrete treated for prohibition of deterioration) and 0.60 (representing deteriorated/high penetrability concrete in need for rehabilitation). the wettability and initial transport characteristics of the coated concrete specimens were determined. In addition, the durability of superficially treated concrete specimens was examined under two aggressive exposures: full submergence in a 5% (by volume) sulfuric acid solution, and 5% sulfuric acid solution combined with wetting-drying cycles. During both exposures, the deterioration of concrete specimens was observed by visual inspection and quantified in terms of mass change. Furthermore, the damage mechanisms and coatings’ performance were studied by microstructural, mineralogical, and thermal analyses. The overall results showed that vinyl ester and vinyl ester nanocomposites significantly improved the durability of concrete specimens by an average of around 64% relative to that of the silane and silane nanocomposites; hence, they are recommended for field applications.

Proton Pump Inhibitors in Pediatric Gastroesophageal Reflux Disease: A Systematic Review of Randomized Controlled Trials.

This systematic review was conducted with the objective of understanding the efficacy and safety of proton pump inhibitors (PPIs) in the pediatric population. We used PubMed to identify randomized controlled trials (RCTs) published between 1 June 2010 and 30 June 2023, performed in patients from birth to 18 years old with gastroesophageal reflux disease (GERD) who received treatment with any PPI. This literature search yielded 76 articles and 13 of these met the inclusion criteria. For infants, PPIs were equal to placebos in reducing GERD symptoms in four articles. In one article, the numbers of GER episodes and esophageal acid exposures were lower in infants who received PPIs in the left lateral position, but there was generally no significant improvement in symptoms. In another publication, the combination of PPIs and feeding modifications (FMs) was not more effective than PPIs alone. For children and adolescents, PPIs were effective in improving symptoms and achieving endoscopic healing, which was subsequently maintained. To conclude, PPIs are not effective in reducing the symptoms related to GERD in infants but are effective in older children, where histological remission can be seen. Generally, PPIs are well tolerated, but it is important to remember the possible adverse events (AEs), especially if PPIs are used for an extended period.