Changes In Reactivity Research Articles

Nephrogenic Adenoma: A Pitfall on Frozen Section of Urethral Strictures.

Urethral strictures are a common cause of urinary obstruction which can be treated with surgical resection. Frozen sections are rare and pose a diagnostic challenge to pathologists due to the presence of benign lesions such as nephrogenic adenoma. We retrospectively examined all specimens of urethral stricture resections submitted to pathology at our institution from 2012 to 2022 (n = 258). Final pathology reports were searched to identify patients with dysplasia, carcinoma, or nephrogenic adenoma. When available, frozen section reports were also examined and compared to the final report, and additional clinical history and microscopic images were collected for patients with nephrogenic adenoma. Nephrogenic adenoma was identified in 3.8% (10/258) of urethral stricture resections. Dysplasia was identified in one patient who underwent two separate resections, and squamous cell carcinoma was found in one resection. Intraoperative frozen section was requested in 3.4% of resections (9/258). In two resections, an initial diagnosis of squamous cell carcinoma was initially favoured, however when reviewed with a genitourinary pathologist the diagnosis was changed to "reactive process" with a final diagnosis of nephrogenic adenoma. Nephrogenic adenoma can be challenging on frozen section due to variable architectural patterns, inflammation, and reactive changes. While urethral strictures are relatively common, their assessment by frozen section is rare and pathologists may lack familiarity with the variable morphology of benign entities that can be seen on frozen section resulting in their misinterpretation. We highlight this potential diagnostic pitfall and demonstrate the value of a second opinion prior to definitive frozen section diagnosis of malignancy.

Mechanisms of psilocybin on the treatment of posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a condition that can develop after a traumatic event, causing distressing symptoms, including intrusive re-experiencing symptoms, alterations in mood and cognition, and changes in arousal and reactivity. Few treatment options exist for patients who find conventional psychotherapy and pharmacotherapy to be inaccessible, ineffective, or intolerable. We explore psilocybin as a potential treatment option for PTSD by examining the neurobiology of PTSD as well as psilocybin's mechanism of action. Based on both pharmacodynamic and psychoanalytic principles, psilocybin may be an underexplored treatment option for patients with PTSD, though further research is required.

The effects of radiofrequency electromagnetic radiation emitted by mobile phones on rat parotid gland histology - an experimental study.

The advancement of telecommunication technology and devices promptly transformed mobile phones into indispensable objects in our day-to-day lives, but their biological effects remain unclear. Therefore, this study aimed to investigate the potential histopathological changes induced by mobile phone radiation in the parotid gland and the nearby tissues. Thirty female Rattus Norvegicus rats were divided into three groups: group 1 (exposed for 30 days), group 2 (exposed for 60 days), and control group (non-exposed). Each subject was exposed to mobile phone radiation in the form of a phone call for two hours every day for their subsequent exposure time. The exposure was always directed towards the same side of the face throughout the whole exposure period. At the end of the exposure period, a comprehensive examination was conducted, including inspection of the orofacial structures, tissue sections of the parotid glands, overlying skin, oral mucosa, and cervical lymph nodes, as well as obtaining smears from the oral cavity. To highlight the presence of micronuclei within the exfoliated squamous cells of the oral epithelium, Feulgen stain was performed. The results showed a significant activation of the fibroblasts in the parotid gland septa, in both exposed experimental groups, compared to the control group. We also detected significant cervical lymph node reactive changes, hyperkeratosis of the oral epithelium, and activated fibroblasts in the dermis and oral mucosa lamina propria in both experimental groups. Dermal fibrosis and lamina propria fibrosis were significantly increased in the second experimental group, compared to the control group. Moreover, vascular congestion in the parotid gland, dermal, and lamina propria fibrosis were significantly increased in the second study group compared to the first one. These findings suggest that exposure to mobile phone radiation may lead to pathological changes in the parotid gland and nearby tissues of experimental rats.

Modeling Polystyrene Nanoplastics Degradation in Water via Photo-Fenton Treatment: A Shrinking-Particle Approach

In this study, kinetic models for the photo-Fenton oxidation of polystyrene nanoplastics (NPs) in water were developed, considering particles with decreasing diameters. Various reaction parameters affecting the oxidation rate, such as particle size (140−909nm), agitation speed (250−1000rpm), and operating temperature (25 and 60 °C) were investigated. Oxidation progress was evaluated through turbidity measurements, TEM, and FTIR analysis, while leached intermediates were identified via Pyr-GC-MS and IC. Due to changes in NPs surface reactivity, the overall reaction rate was divided into two stages, following a free-radical mechanism. Using equations derived from the classic Shrinking Core Model, the oxidation of NPs was determined to proceed under chemical reaction control, with negligible mass transfer limitations. Additionally, the Prout-Tompkins model was found to accurately represent the degradation process. The proposed mechanisms and models provide valuable insights for describing and predicting the advanced oxidation of NPs under different operating conditions and treatment methods.

Effect of chloride ions on the reactive species change pathway and removal performance in the MW/Co2+/PMS process

Efficient removal of refractory organic matter is the focus of research in the treatment of actual wastewater with Peroxymonosulfate-based advanced oxidation processes(PMS-AOPs). However, the high concentration of chloride ions (Cl−) ubiquitously present in wastewater changes the reactive species (RS) present in the process, and the mechanism of this change is still not clear. This study investigated the effects of Cl− on the transformation behavior of RS and treatment performance under microwave (MW) combined with cobalt ions (Co2+)-activated PMS. The results showed that increasing the Cl− concentration can enhance the removal performance of the MW/Co2+/PMS process for ammonia (NH4+-N), accompanied by the production of nitrate nitrogen (NO3-N), monochloramine (NH2Cl) and dichloramine (NHCl2), which was related to the transformation of existing reactive oxygen species (ROS, •OH and SO4•−) into reactive chlorine species (RCS), with hypochlorous acid (HClO) as an important intermediate. Cl− can generate HClO through free radical oxidation (•OH and SO4•−) dominance and non-free radical oxidation (PMS and Co3+) promotion, and the heat transferred by MW can further trigger conversion between HClO and PMS, thereby changing the distribution of RS. Increasing the dosage of PMS and the dosage of Co2+ promoted the transformation of Cl− to reactive species in the MW/Co2+/PMS process. At MW power=160W, [Co2+]=17.5μM,[PMS]=10mM, and [Cl−]=17mM, the maximum cumulative [HClO] reached 1910.97μM, and the decay rate was 0.1815 min-1.The macromolecular organic matter in aqueous environment competes with ammonia for the RCS. Through regulating [Cl−] in mature leachate, RCS has a certain oxidation effect to organic matter, but its limited oxidation ability leads to a decrease in the mineralization effect.

From Graphene Oxide to Graphene: Changes in Interfacial Water Structure and Reactivity Using Deep Neural Network Force Fields

From Graphene Oxide to Graphene: Changes in Interfacial Water Structure and Reactivity Using Deep Neural Network Force Fields

Neonatal inflammation impairs developmentally-associated microglia and promotes a highly reactive microglial subset

Microglia and border-associated macrophages play critical roles in both immunity and neurodevelopment. The disruption of microglial development trajectories by neonatal inflammation is an important issue in research on neurodevelopmental disorders (NDDs), as models have suggested a strong association between inflammation and cognitive deficits. Here, we explored by single-cell RNA sequencing and flow cytometry the impact of neonatal inflammation in a mouse NDD model on brain myeloid cell subsets. A specific subset of microglia expressing the complement receptor C5ar1 has been identified, in which inflammatory pathways are most strongly activated. Based on transcriptional similarity, this subset appears to originate from the most mature and “homeostatic“ microglia at this stage of development and demonstrated hypersensitivity to inflammation. Besides that, Spp1-microglia supporting oligodendrocyte differentiation, primitive and proliferative microglia were reduced by inflammation. These findings suggest major changes in microglial subsets developmental trajectories and reactivity contributing to NDDs induced by neonatal inflammation.

Abstract C080: Glioma cell-mediated hyper-thrombotic tumor microenvironment drives glioblastoma growth

Abstract Cancer-related thrombosis is the second leading cause of death for cancer patients, including those with glioblastoma (GBM), the most common primary malignant brain tumor. Patients with GBM have a 30% risk of venous thromboembolism (VTE). High platelet counts, and increased platelet reactivity are associated with poor clinical outcomes in many cancers. While platelets are known to promote progression of tumors, the mechanisms by which these changes in platelet reactivity act as a driver for GBM progression is unknown. Our previous work demonstrated that a subpopulation of glioma cells activates platelets to promote GBM cell growth by intrinsically producing thrombin via a cell intrinsic functional coagulation cascade. These findings provided evidence that glioma cells can readily execute a highly liver-specific gene expression program that contributes to a hyper-thrombotic state in the GBM tumor microenvironment (TME). We now demonstrate thrombin and platelet expression in GBM patient specimen creates a hyper-thrombotic GBM tumor-microenvironment and that GBM patient platelets have increased reactivity compared to healthy patients. Further, genetic targeting of the intrinsic coagulation cascade, via knockdown of coagulation factor 11 (F11) and coagulation factor 12 (F12), reduces glioma cell growth and tumor formation while also decreasing the ability for glioma cells to activate platelets, subsequently decreasing the hyper-thrombotic state seen in the GBM tumor microenvironment. Our observations suggest that glioma cells execute a cell intrinsic coagulation mechanism to contribute to the hyper-thrombotic tumor-microenvironment seen in GBM and may shed light onto mechanisms of cancer associated thrombosis in not only GBM, but also other malignancies. Citation Format: George Bukenya, Anthony Sloan, Craig Horbinski, Anirban Sen Gupta, Scott Cameron, Justin Lathia. Glioma cell-mediated hyper-thrombotic tumor microenvironment drives glioblastoma growth [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C080.

Dissimilar Trypanosoma cruzi genotype-specific serological profile assessed by Chagas-Flow ATE IgG1 upon benznidazole etiological treatment of chronic Chagas disease.

The present study aimed to verify the impact of etiological treatment on the genotype-specific serological diagnosis of chronic Chagas disease patients (CH), using the Chagas-Flow ATE IgG1 methodology. For this purpose, a total of 92 serum samples from CH, categorized as Not Treated (NT, n = 32) and Benznidazole-Treated (Bz-T, n = 60), were tested at Study Baseline and 5Years Follow-up. At Study Baseline, all patients have the diagnosis of Chagas disease confirmed by Chagas-Flow ATE IgG1, using the set of attributes ("antigen/serum dilution/cut-off"; "EVI/250/30%"). The genotype-specific serodiagnosis at Study Baseline demonstrated that 96% of patients (44/46) presented a serological profile compatible with TcII genotype infection. At 5Years Follow-up monitoring, NT and Bz-T presented no changes in anti-EVI IgG1 reactivity. However, significant differences were detected in the genotype-specific IgG1 reactivity for Bz-T. The most outstanding shift comprised the anti-amastigote TcVI/(AVI), anti-amastigote TcII/(AII) and anti-epimastigote TcVI/(EVI) reactivities. Regardless no changes in the genotype-specific serology of NT (TcI = 6%; TcII = 94%), distinct T. cruzi genotype-specific sero-classification was detected for Bz-T samples at 5Years Follow-up (TcII = 100%) as compared to Baseline (TcII = 97%; TcVI = 3%). The anti-trypomastigote TcI/(TI) was the attribute accountable for the change in genotype-specific sero-classification. In conclusion, our findings of dissimilar T. cruzi genotype-specific serology upon Bz-treatment re-emphasize the relevance of accomplishing the genotype-specific serodiagnosis during clinical pos-therapeutic management of chronic Chagas disease patients.

Single-cell, single-nucleus and xenium-based spatial transcriptomics analyses reveal inflammatory activation and altered cell interactions in the hippocampus in mice with temporal lobe epilepsy

BackgroundTemporal lobe epilepsy (TLE) is among the most common types of epilepsy and often leads to cognitive, emotional, and psychiatric issues due to the frequent seizures. A notable pathological change related to TLE is hippocampal sclerosis (HS), which is characterized by neuronal loss, gliosis, and an increased neuron fibre density. The mechanisms underlying TLE-HS development remain unclear, but the reactive transcriptomic changes in glial cells and neurons of the hippocampus post-epileptogenesis may provide insights.MethodsTo induce TLE, 200 nl of kainic acid (KA) was stereotactically injected into the hippocampal CA1 region of mice, followed by a 7-day postinjection period. Single-cell RNA sequencing (ScRNA-seq), single-nucleus RNA sequencing (SnRNA-seq), and Xenium-based spatial transcriptomics analyses were employed to evaluate the changes in mRNA expression in glial cells and neurons.ResultsFrom the ScRNA-seq and SnRNA-seq data, 31,390 glial cells and 48,221 neuronal nuclei were identified. Analysis of the differentially expressed genes (DEGs) revealed significant transcriptomic alterations in the hippocampal cells of mice with TLE, affecting hundreds to thousands of mRNAs and their signalling pathways. Enrichment analysis indicated notable activation of stress and inflammatory pathways in the TLE hippocampus, while pathways related to axonal development and neural support were suppressed. Xenium analysis demonstrated the expression of all 247 genes across mouse brain sections, revealing the spatial distributions of their expression in 27 cell types. Integrated analysis of the DEGs identified via the three sequencing techniques revealed that Spp1, Trem2, and Cd68 were upregulated in all glial cell types and in the Xenium data; Penk, Sorcs3, and Plekha2 were upregulated in all neuronal cell types and in the Xenium data; and Tle4 and Sipa1l3 were downregulated in all glial cell types and in the Xenium data.ConclusionIn this study, a high-resolution single-cell transcriptomic atlas of the hippocampus in mice with TLE was established, revealing potential intrinsic mechanisms driving TLE-associated inflammatory activation and altered cell interactions. These findings provide valuable insights for further exploration of HS development and epileptogenesis.

Amygdala Reactivity, Antidepressant Discontinuation, and Relapse

Antidepressant discontinuation substantially increases the risk of a depression relapse, but the neurobiological mechanisms through which this happens are not known. Amygdala reactivity to negative information is a marker of negative affective processes in depression that is reduced by antidepressant medication, but it is unknown whether amygdala reactivity is sensitive to antidepressant discontinuation or whether any change is related to the risk of relapse after antidepressant discontinuation. To investigate whether amygdala reactivity to negative facial emotions changes with antidepressant discontinuation and is associated with subsequent relapse. The Antidepressiva Absetzstudie (AIDA) study was a longitudinal, observational study in which adult patients with remitted major depressive disorder (MDD) and currently taking antidepressants underwent 2 task-based functional magnetic resonance imaging (fMRI) measurements of amygdala reactivity. Patients were randomized to discontinuing antidepressants either before or after the second fMRI measurement. Relapse was monitored over a 6-month follow-up period. Study recruitment took place from June 2015 to January 2018. Data were collected between July 1, 2015, and January 31, 2019, and statistical analyses were conducted between June 2021 and December 2023. The study took place in a university setting in Zurich, Switzerland, and Berlin, Germany. Of 123 recruited patients, 83 were included in analyses. Of 66 recruited healthy control individuals matched for age, sex, and education, 53 were included in analyses. Discontinuation of antidepressant medication. Task-based fMRI measurement of amygdala reactivity and MDD relapse within 6 months after discontinuation. Among patients with MDD, the mean (SD) age was 35.42 (11.41) years, and 62 (75%) were women. Among control individuals, the mean (SD) age was 33.57 (10.70) years, and 37 (70%) were women. Amygdala reactivity of patients with remitted MDD and taking medication did not initially differ from that of control individuals (t125.136 = 0.33; P = .74). An increase in amygdala reactivity after antidepressant discontinuation was associated with depression relapse (3-way interaction between group [12W (waited) vs 1W2 (discontinued)], time point [MA1 (first scan) vs MA2 (second scan)], and relapse: β, 18.9; 95% CI, 0.8-37.1; P = .04). Amygdala reactivity change was associated with shorter times to relapse (hazard ratio, 1.05; 95% CI, 1.01-1.09; P = .01) and predictive of relapse (leave-one-out cross-validation balanced accuracy, 67%; 95% posterior predictive interval, 53-80; P = .02). An increase in amygdala reactivity was associated with risk of relapse after antidepressant discontinuation and may represent a functional neuroimaging marker that could inform clinical decisions around antidepressant discontinuation.

Immune responses of pulpodentinal complex during caries progression

Caries is an infectious disease in which the invasion of pathogens and their metabolites can activate the recognition and defense system of the pulpodentinal complex. In-depth understanding of the immune responses mediated by the pulpodentinal complex will help to estimate the real state of the dental pulp during the progression of caries and to take reasonable clinical treatment strategies, which can be more targeted and less invasive. Based on the physiology of the pulpodentinal complex, the present article introduce its immunocompetence and mechanism, reactive changes, clinical intervention and its significance during the caries progression, as to improve diagnostics as well as treatment strategies for caries.

EP58 - Gangrenous appendicitis in an incarcerated femoral hernia: A rare case of De Garengeot Hernia

Abstract Aims To present a rare case of gangrenous appendicitis within an incarcerated femoral hernia, discussing its clinical background and highlighting the challenges in its diagnosis and surgical management. Methods We detail a 74-year-old female with a painful, non-reducible groin mass. A CT abdomen pelvis revealed a right femoral hernia with acute reactive inflammatory changes, with no comment made on the appendix (Figure 1 and 2). Emergency open femoral hernioplasty and laparoscopic appendectomy were performed. Results Intraoperatively, a femoral hernia with a gangrenous appendicitis were identified. The appendix was reduced into the abdominal cavity to allow for better evaluation of its base. A laparoscopic appendectomy was performed after identifying the healthy base (Figure 3), followed by a femoral hernioplasty. This case sheds light on the rarity not only of the De Garengeot hernia which is defined by the presence of the vermiform appendix within the femoral hernia sac, but also even rarer the finding of a gangrenous appendix within the sac, with a reported incidence from 0.08-0.13% in cases of acute appendicitis. The case emphasizes the importance of considering an acute appendicitis and its complications within a femoral hernia as a differential diagnosis of painful groin masses with raised inflammatory markers. Conclusion Given the scarcity of literature on the surgical management of acute appendicitis in De Garengeot hernias, this case contributes valuable insights. The absence of established guidelines underscores the need for further exploration of optimal surgical strategies in such cases. Our report aims to enhance awareness of this rare presentation and facilitate future discussions on its management.

Purkinje Cell Dendritic Swellings: A Postmortem Study of Essential Tremor and Other Cerebellar Degenerative Disorders.

Under stress, Purkinje cells (PCs) undergo a variety of reactive morphological changes. These can include swellings of neuronal processes. While axonal swellings, "torpedoes", have been well-studied, dendritic swellings (DS) have not been the centerpiece of study. Surprisingly little is known about their frequency or relationship to other morphological changes in degenerating PCs. Leveraging a large brain bank, we (1) examined the morphology of DS, (2) quantified DS, and (2) examined correlations between counts of DS versus 16 other PC morphological changes in a broad range of cerebellar degenerative disorders. There were 159 brains - 100 essential tremor (ET), 13 Friedreich's ataxia, and 46 spinocerebellar ataxia (SCA) (14 SCA1, 7 SCA2, 13 SCA3, 5 SCA6, 5 SCA7, and 2 SCA8). DS were a feature of PCs across all these disorders, with varying morphologies and changes elsewhere in the dendritic arbor. On Luxol fast blue/hematoxylin and eosin-stained sections, the median number of DS per PC ranged from 0.001 in ET to 0.025 in SCA8. Bielschowsky-stained sections yielded higher counts, from 0.003 in ET to 0.042 in SCA6. Torpedo counts exceeded DS counts by one order of magnitude. DS counts were more robustly correlated with torpedo counts than with counts for any of the other PC morphological changes. In summary, DS ranged in prevalence across cerebellar degenerative disorders, from 1/1,000 to 42/1,000 PCs. Across disorders of cerebellar degeneration, these swellings of the dendritic compartment were most robustly correlated with swellings of the axonal compartment, suggesting a similar type of cellular response to duress.

Stable and Reusable Pd/Cu Bimetallic Nanoparticle Catalysts for the Synthesis of Hydroxy Isoindolones by Domino C−H Activation and Annulation

AbstractA domino C−H activation and annulation process catalyzed by stable and reusable bimetallic nanoparticles (Pd/Cu‐binapthyl nanoparticles) was developed for the synthesis of 3‐hydroxyisoindolin‐1‐ones/thiones. The scope of the reaction was examined utilizing a variety of N‐alkoxy benzamide/benzothioamide derivatives and benzaldehydes, which yielded moderate to good yields of 3‐hydroxyisoindolin‐1‐ones/thiones, one of which was used to synthesize a BRD4 inhibitor. A gram‐scale synthesis is also reported. The Pd/Cu‐binapthyl nanocatalyst has been recovered and reused up to four times without any major change in particle size and reactivity.

A Computational Analysis of the Proton Affinity and the Hydration of TEMPO and Its Piperidine Analogs.

The study investigated the impact of protonation and hydration on the geometry of nitroxide radicals using B3LYP and M06-2X methods. Results indicated that TEMPO exhibited the highest proton affinity in comparison to TEMPOL and TEMPONE. Two pathways contribute to hydrated protonated molecules. TEMPO shows lower first enthalpies of hydration (ΔH1-M), indicating stronger H-bonding interactions, while TEMPONE shows higher values, indicating weaker interactions with H2O. Solvent effects affect charge distribution by decreasing their atomic charge. Spin density (SD) is primarily concentrated in the NO segment, with minimal water molecule contamination. Protonation increases SD on N-atom, while hydration causes a more pronounced redistribution for water molecules. The stability of the dipolar structure (>N·+-O-) is evident in SD redistributions. The frontier molecular orbital (FMO) analysis of TEMPONE reveals a minimum EHOMO-LUMO gap (EH-L), enhancing the piperidine ring's reactivity. TEMPO is the most nucleophilic species, while TEMPONE exhibits strong electrophilicity. Transitioning from NO radicals to protonated forms increases the EH-L gap, indicating protonation stabilizes FMOs. Increased water molecules make the molecule less reactive, while increasing hydration decreases this energy gap, making the molecule more reactive. A smaller EH-L gap indicates the compound becomes softer and more prone to electron density and reactivity changes.

Prazosin Treatment of Sleep Problems in Youth with PTSD

Post traumatic stress disorder (PTSD) is a condition characterized by reexperiencing symptoms, persistent avoidance, negative alterations in cognition and mood, and changes in arousal and reactivity in response to a traumatic event (American Psychiatric Association, 2013). The pathophysiology of PTSD is not fully understood but likely related to dysregulation of fear‐processing. Currently, the gold standard of treatment is trauma‐focused cognitive behavioral therapy (TF‐CBT). SSRIs are the only FDA‐approved pharmacologic treatments for PTSD in adults and there are no FDA approved medications to treat pediatric PTSD. Unlike studies in adults, double‐blinded randomized control trials (RCTs) did not show any efficacy for SSRIs in pediatric patients diagnosed with PTSD (Hudson et al., 2021). While estimates of pediatric PTSD prevalence varies, the prevalence of PTSD at age 18 is 7.8% (Rolling et al., 2023). Sleep disturbances such as insomnia, night‐time awakenings, and nightmares often persist despite treatment with TF‐CBT or SSRIs. Left untreated, sleep disturbances are predictive of PTSD persistence and comorbid psychiatric complications (Rolling et al., 2023). There is evidence supporting the use of the medication prazosin in alleviating pediatric PTSD sleep disturbances including nightmares and insomnia. Anywhere from 20–80% of children with PTSD report nightmares compared to a prevalence of 10–20% in the general pediatric population (Kovachy et al., 2013). There is a growing need for pharmacologic therapy given the paucity of providers trained in TF‐CBT and a need for symptomatic management. In this review, we will examine sleep disturbances in pediatric PTSD patients and discuss the feasibility of prazosin as an adjunct treatment option.

435. PREVALENCE OF OESOPHAGEAL PREMALIGNANT LESIONS AMONG PATIENTS REFERRED FOR GASTRO-OESOPHAGEAL-DUODENOSCOPY AT A TERTIARY CARE HOSPITAL IN NORTHERN, SRI LANKA

Abstract Background Oesophageal cancer is the second leading cause of cancer-related mortality in Sri Lanka, where a higher prevalence is found among Tamil-speaking Sri Lankans. Endoscopic screening with Lugol’s chromo endoscopy in high-incidence populations reduces mortality from oesophageal cancer. The objective of this study is to determine the prevalence of premalignant oesophageal lesions - squamous dysplasia and Barrett’s oesophagus and the associated risk factors among Tamil patients undergoing oesophageal-gastro-duodenoscopy (OGD). Methods Consecutive patients undergoing OGD for dyspeptic and gastric acid reflux symptoms were recruited. An interviewer-administered questionnaire was used for data collection. During OGD, the oesophagus was examined under white light imaging, narrow band imaging (NBI), and Lugol’s iodine chromo endoscopy. Biopsies were taken from abnormal mucosa and sent for pathological diagnosis. Statistical software SPSS (V25) was used to analyse the data. Results The study incorporates 410 participants. The majority (61.7%) were females and the median age was 57 (Interquartile range 21) years. On Endoscopy under white light and NBI 11.0%(n=45) had squamous neoplasia. Of them, 16.0% had Low grade dysplasia (LGD), 2.0% had invasive carcinoma and the remaining 82.0% had inflammatory or reactive changes. Endoscopic Barrett’s oesophagus (BO) was found in 17.0% (n=69) and 5.0% (n=19) had both endoscopic and histological confirmation of BO. Of them, 21.0% had LGD. In regression analysis, male gender was at higher risk for BO (OR- 1.251, 95%CI 0.420 – 3.730). Overall, 3.0% of the participants had premalignant lesions. Conclusions The prevalence of premalignant lesions in a symptomatic population was only 3.0%. Further studies with a larger number of targeted population is needed to assess the exact prevalence.

Abstract 59: Beclin-1-Dependent Autophagy Prevents Hyperaldosternism-Induced Endothelial Dysfunction And Hypertension

Hyperaldosteronism (HA), characterized by the overproduction of aldosterone (Aldo), leads to cardiovascular damage, including endothelial dysfunction. Beclin-1 (Becn1) is a key protein regulating autophagy, a recycling process for unwanted components. Whether HA disturbs autophagic flux in endothelial cells via Becn1 is unknown. We hypothesize that Becn1-dependent autophagic flux will improve endothelial function and inhibit the hypertension (HTN) in HA. 10-to-12-week-old male C57BL/6J (WT) or Becn1 knock-in mice (Becn1 Tg ) were infused with aldosterone for 14 days (600 µg/kg/day). Vascular function was studied in mesenteric arteries (MA) and blood pressure was analyzed by radiotelemetry. HA disrupted MA autophagic flux characterized by accumulation of LC3A/B and p62 and reduction in Becn1 expression and activity followed by suppressed acetylcholine (ACh)-induced vasodilation (% relaxation) in WT [WT: 91.5±1.1 vs HA: 56.7±2.7], whereas Becn1 Tg mice were protected from HA-induced HTN [mean blood pressure (mmHg) – WT_Aldo: 149.1±1.2 vs BCN1_Aldo: 118.1±0.8] and endothelial dysfunction [HA_Becn1 Tg : 92.8±2.9]. Given the link between the immune system and cardiovascular diseases, we investigated whether HA reduces autophagic flux and BCN1 in immune cells. HA led to the accumulation of LC3A/B and p62, and decreased BCN1 activity in peritoneal cavity cells of WT mice, however bone marrow transplant from Becn1 Tg mice into WT mice did not confer protection against HA-induced changes in vascular reactivity [WT to WT_HA: 51.2±1.3 vs Becn1 Tg to WT_HA: 53.8±1.9]. As a pharmacological approach, we accelerated autophagic flux by treating mice with spermidine (3 mM for 7 days), which subsequently improved endothelial function in HA [HA: 52.7±3.9 vs HA+spermidine: 88.9±3.9]. To assess the direct impact of Aldo on disrupting autophagy flux in endothelial cells, we treated mesenteric endothelial cells (MEC) with Aldo (0.1 µM for 24 hours). This treatment resulted in the accumulation of LC3A/B and p62 proteins and a reduction in BCN1 activity, accompanied by an upregulation in the mRNA expression of pro-inflammatory cytokines. All these effects were prevented by spermidine (100 uM for 3h). These findings reveal a novel pathway in HA-associated endothelial dysfunction and HTN, where Aldo disrupts autophagic flux and inflammation by suppressing BCN1 activity, positioning BCN1 as a pharmacological target for cardiovascular outcomes in HA.

Piperine Enhances the Anticancer Effects of Cisplatin on Tongue Squamous Cell Carcinoma Cell Line by Inducing Cell Apoptosis.

Oral squamous cell carcinoma is ranked as the predominant type of head and neck squamous cell carcinoma, comprising roughly 90% of all oral cancer cases. Natural products have proven to be highly valuable as complementary, or adjunctive in the treatment of cancer. Piperine, a natural compound derived from Piper nigrum, demonstrates anti-proliferative and anti-neoplastic effects across various types of cancer. This study focused on assessing the cytotoxic effect of piperine in conjunction with cisplatin within the OSCC cell line. In this in-vitro study, cultured OSCC cells were divided into four groups: a control group (untreated), a group exposed solely to piperine, a group exposed solely to cisplatin, and a group receiving both piperine and cisplatin. Cell viability was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assay technique. Additionally, flow cytometric analysis was employed to examine cell cycle progression and apoptosis. Assessment of reactive oxygen species activity, morphological changes, and nuclear area factor measurements were carried out. Expression of the apoptotic regulator Bax was assessed through western blotting analysis. Piperine has cytotoxic and apoptotic effects in a concentration-dependent manner. Piperine in combination with cisplatin exhibited a synergistic effect, resulting in more pronounced inhibition of cell viability in OSCC cells compared to using piperine and cisplatin alone. Piperine and cisplatin for 24 h induced apoptosis strongly by increasing Bax protein and ROS activity. Combining piperine with cisplatin demonstrated a greater effectiveness in triggering apoptosis in OSCC cells compared to using cisplatin alone, allowing for a reduction.