Excessive Response Research Articles

Understanding the Acid-Base Response to Respiratory Derangements: Finding, and Clinically Applying, the In Vivo Base Excess.

To evaluate the base excess response during acute in vivo carbon dioxide changes. Secondary analysis of individual participant data from experimental studies. Three experimental studies investigating the effect of acute in vivo respiratory derangements on acid-base variables. Eighty-nine (canine and human) carbon dioxide exposures. Arterial carbon dioxide titration through environmental chambers or mechanical ventilation. For each subject, base excess was calculated using bicarbonate and pH using a fixed buffer power of 16.2. Analyses were performed using linear regression with arterial dioxide (predictor), base excess (outcome), and studies (interaction term). All studies show different baselines and slopes for base excess across carbon dioxide titrations methods. Individual subjects show substantial, and potentially clinically relevant, variations in base excess response across the hypercapnic range. Using a mathematical simulation of 10,000 buffer power coefficients we determined that a coefficient of 12.1 (95% CI, 9.1-15.1) instead of 16.2 facilitates a more conceptually appropriate in vivo base excess equation for general clinical application. In vivo changes in carbon dioxide leads to changes in base excess that may be clinically relevant for individual patients. A buffer power coefficient of 16.2 may not be appropriate in vivo and needs external validation in a range of clinical settings.

Vehicle Mass Estimation via Practical Supervisory Artificial Neural Networks Using Perturbed Engine Torque and Acceleration Inputs

Various model-based mass estimation approaches have been discussed for a long time. However, estimation performance often deteriorates in some driving situations and, in particular, slow convergence and excessive overshoot of estimates are a major issue for model-based approaches. Meanwhile, mass estimation approaches using ANN models have recently emerged to propose better solutions, but their usefulness has not been fully investigated. Therefore, this paper presents a vehicle mass estimation strategy using practical supervisory artificial neural networks to achieve more accurate results with better convergence. Here, the perturbed engine torque and vehicle longitudinal acceleration are selected as the inputs of the ANN (instead of the original engine torque and vehicle acceleration), which allows for the faster convergence of estimates with high accuracy; these inputs are existing sensor values already available in the vehicle system. The effectiveness of the proposed ANN approach was verified using simulation and software-in-the-loop simulation (SILS) with field test data, and it was found that the convergence speed of the proposed ANN is almost twice as fast as that of the model-based approach, the accuracy is much better, and the estimation quality is constantly stable without any excessive transient responses. This study will provide further insights into mass estimation using the ANN approach.

Secretory leukocyte protease inhibitor influences periarticular joint inflammation in B. burgdorferi -infected mice.

Lyme disease, caused by Borrelia burgdorferi , is the most common tick-borne infection in the United States. Arthritis is a major clinical manifestation of infection, and synovial tissue damage has been attributed to the excessive pro-inflammatory responses. The secretory leukocyte protease inhibitor (SLPI) promotes tissue repair and exerts anti-inflammatory effects. The role of SLPI in the development of Lyme arthritis in C57BL/6 mice, which can be infected with B. burgdorferi , but only develop mild joint inflammation, was therefore examined. SLPI -deficient C57BL/6 mice challenged with B. burgdorferi had a higher infection load in the tibiotarsal joints and marked periarticular swelling, compared to infected wild type control mice. The ankle joint tissues of B. burgdorferi- infected SLPI -deficient mice contained significantly higher percentages of infiltrating neutrophils and macrophages. B. burgdorferi -infected SLPI -deficient mice also exhibited elevated serum levels of IL-6, neutrophil elastase, and MMP-8. Moreover, using a recently developed BASEHIT ( BA cterial S election to E lucidate H ost-microbe I nteractions in high T hroughput) library, we found that SLPI directly interacts with B. burgdorferi . These data demonstrate the importance of SLPI in suppressing periarticular joint inflammation in Lyme disease.

Balancing Growth and Defense: Nanoselenium and Melatonin in Tea (Camellia sinensis) Protection against Glufosinate.

Current crop stress resistance research suggests that the prominent stimulants nanoselenium (NSe) and melatonin (MT) might improve tea safety, quality, and stress resistance induced by the widely used nonselective herbicide glufosinate (GLU). Their biofortification effects on tea growth, antioxidant activity, and secondary metabolism pathways response to GLU remain unclear. Here, NSe, MT, and their combination NSe-MT effectively reduced 26.6-50.9% GLU and its metabolites in tea seedlings, balanced the photosystem, enhanced antioxidant defenses, and optimized reactive oxygen species scavenging mechanisms. Further, GLU-induced inhibition of glutamine synthetase (11.2-34.0%), ammonium toxicity (55.0-64.7%), and nitrogen metabolism disorders were alleviated. Stimulants exhibited different preferences in the accumulation of l-theanine (8.4-47%), gamma-aminobutyric acid (10.3-41.7%), and catechins (13.1-73.1%, excluding ECG), thereby influencing tea quality. Transcriptomic and metabolomic analyses validated that NSe-MT had a more pronounced impact on tender tea leaves than individual stimulant treatments. All stimulants reduced GLU-induced excessive jasmonic acid (29.8-50.5%) production and signaling responses, revealing their significance in crop physiological activities under herbicide or nitrogen stress. The reduction in aromatic amino acids helped mitigate GLU's interference with phenylpropanoid biosynthesis, leading to inhibited lignin production but enhanced nutritional flavonoid levels, such as catechins. NSe and NSe-MT demonstrated promising potential as herbicide safeners. These findings provided insights into GLU detoxification mechanisms in other nontarget crops as well.

Study of excess manganese stress response highlights the central role of manganese exporter Mnx for holding manganese homeostasis in the cyanobacterium Synechocystis sp. PCC 6803.

Cellular levels of the essential micronutrient manganese (Mn) need to be carefully balanced within narrow borders. In cyanobacteria, a sufficient Mn supply is critical for ensuring the function of the oxygen-evolving complex as the central part of the photosynthetic machinery. However, Mn accumulation is fatal for the cells. The reason for the observed cytotoxicity is unclear. To understand the causality behind Mn toxicity in cyanobacteria, we investigated the impact of excess Mn on physiology and global gene expression in the model organism Synechocystis sp. PCC 6803. We compared the response of the WT and the knock-out mutant in the Mn exporter (Mnx), ∆mnx, which is disabled in the export of surplus Mn and thus functions as a model for toxic Mn overaccumulation. While growth and pigment accumulation in ∆mnx were severely impaired 24 h after the addition of tenfold Mn, the WT was not affected and thus mounted an adequate transcriptional response. RNA-seq data analysis revealed that the Mn stress transcriptomes partly resembled an iron limitation transcriptome. However, the expression of iron limitation signature genes isiABDC was not affected by the Mn treatment, indicating that Mn excess is not accompanied by iron limitation in Synechocystis. We suggest that the ferric uptake regulator, Fur, gets partially mismetallated under Mn excess conditions and thus interferes with an iron-dependent transcriptional response. To encounter mismetallation and other Mn-dependent problems on a protein level, the cells invest in transcripts of ribosomes, proteases and chaperones. In the case of the ∆mnx mutant, the consequences of the disability to export excess Mn from the cytosol manifest in additionally impaired energy metabolism and oxidative stress transcriptomes with a fatal outcome. This study emphasizes the central importance of Mn homeostasis and the transporter Mnx's role in restoring and holding it.

Investigation of Phytochemical and Antidepressants Activity of Cinnamon Powder Extract

Neurodegenerative disease is the most common type of mobility issue, but unfortunately, there is now no medication that can alter the course of the disease. We don't know what causes this ailment. In mouse models of Parkinson's disease induced with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine, the oral administration of cinnamon powder and sodium benzoate may prevent the death of dopaminergic cells, dysregulation of striatal neurotransmitters, and motor impairments. The mechanisms driving its function include controlling autophagy, antioxidant effects, Parkin, DJ-1, and glial cell line-derived neurotrophic factor activation, TLR/NF-κB pathway modulation, and excessive proinflammatory response prevention. Moreover, research carried out in both laboratory and living organism settings has shown that cinnamon extracts may impact the oligomerisation and aggregation of α-synuclein. This article's goal is to discuss recent findings about this phytochemical's potential as a novel treatment for Parkinson's disease (PD). We highlight additional areas of mechanism that require investigation and possible constraints that must be overcome before this phytochemical may be used in PD trials. Neurodegenerative disease is the most common type of mobility impairment, and unfortunately, there is now no medication that can alter this disease. We don't know what causes this ailment. There has been a recent uptick in interest in medicinal plant use because of the novelty, safety, and relative affordability of this field. The characteristic flavour and aroma of cinnamon, a spice that is often used, may have neuroprotective effects on people with Parkinson's disease (PD) and other neurodegenerative diseases. The essential oils of Cinnamomum species, such as cinnamaldehyde and sodium benzoate, have shown in vitro that they can protect cells from oxidative stress, ROS generation, and autophagy dysregulation. Consequently, these oils may exert a neuroprotective effect. The in vivo evidence suggests that cinnamon powder and sodium benzoate, when administered orally to Parkinson's disease models in mice, may prevent the death of dopaminergic cells, dysregulation of striatal neurotransmitters, and motor deficits. In this essay, we will go over the latest research on this phytochemical and its potential as a novel treatment for Parkinson's disease (PD). Incorporating this phytochemical into experimental PD treatments requires further investigation into additional molecular aspects and the potential overcoming of constraints and obstacles.

Rab11 suppresses neuronal stress signaling by localizing dual leucine zipper kinase to axon terminals for protein turnover.

Dual leucine zipper kinase (DLK) mediates multiple neuronal stress responses, and its expression levels are constantly suppressed to prevent excessive stress signaling. We found that Wallenda (Wnd), the Drosophila ortholog of DLK, is highly enriched in the axon terminals of Drosophila sensory neurons in vivo and that this subcellular localization is necessary for Highwire-mediated Wnd protein turnover under normal conditions. Our structure-function analysis found that Wnd palmitoylation is essential for its axon terminal localization. Palmitoylation-defective Wnd accumulated in neuronal cell bodies, exhibited dramatically increased protein expression levels, and triggered excessive neuronal stress responses. Defective intracellular transport is implicated in neurodegenerative conditions. Comprehensive dominant-negative Rab protein screening identified Rab11 as an essential factor for Wnd localization in axon terminals. Consequently, Rab11 loss-of-function increased the protein levels of Wnd and induced neuronal stress responses. Inhibiting Wnd activity significantly ameliorated neuronal loss and c-Jun N-terminal kinase signaling triggered by Rab11 loss-of-function. Taken together, these suggest that DLK proteins are constantly transported to axon terminals for protein turnover and a failure of such transport can lead to neuronal loss. Our study demonstrates how subcellular protein localization is coupled to protein turnover for neuronal stress signaling.

Performance Evaluation of Inerter and Negative Stiffness-Based Dampers for Seismic-Induced Vibration Response Control of a Cable-Stayed Bridge: A Comparative Study

The excessive main girder displacement responses of the large-span cable-stayed bridges during seismic events may precipitate collisions between the main girder and the approach bridge. The viscous dampers (VDs) have been extensively employed in the seismic response control of long-span bridges, yet their effectiveness is limited. To augment the seismic-induced vibration control performance of the VD, inerter element, negative stiffness (NS) element, and spring element have been incorporated into the VD to achieve energy dissipation capacity enhancement. The equations of motion for the simplified cable-stayed bridge-damper systems are established under stochastic seismic excitation, and the design parameters of inerter and NS-based damper are optimized by using the genetic algorithm. The seismic control performance of the VD and five types of dampers are systematically compared, demonstrating that these dampers can substantially enhance the main girder displacement mitigation performance in cable-stayed bridges. Owing to the NS characteristics attributes of the inerter element and NS element and the tuning effect of the spring element, the tuned viscous mass damper (TVMD) with NS achieves a 24.56% higher efficiency in control performance compared to the VD.

CD14 blockade preserves left ventricular structure and systolic function in a murine model of ST-elevation myocardial infarction

Abstract Background Cluster of differentiation-14 (CD14) facilitates the excessive pro-inflammatory monocyte-macrophage response to myocardial injury. Both acute and chronic infiltration of pro-inflammatory macrophages are implicated in the immunological progression of ischemic heart failure. However, investigation of clinically practicable strategies of CD14 blockade are yet to be reported. Purpose This fully blinded and randomised preclinical study evaluated the efficacy of a neutralising anti-CD14 antibody given at reperfusion in a murine model of reperfused ST-elevation myocardial infarction (STEMI) with key clinical features. Methods Large anterior STEMI was induced in 48 adult mice by left anterior descending coronary artery occlusion for 1 h prior to reperfusion and randomisation to receive anti-CD14 antibody, isotype control (IgG2a) or saline weekly for four weeks (independently blinded). Outcome measures included functional assessments by 9.4T cardiac magnetic resonance (CMR) imaging and ultra-high-resolution echocardiography at 21- and 28-days post-STEMI, respectively. Results Multi-plane short axis CMR at 21-days post-STEMI revealed greater left ventricular (LV) ejection fraction in the anti-CD14 antibody-treated group compared with saline- and isotype-treated controls (30±1 vs 19±1 and 20±1 %, respectively, p<0.001; Figure 1A). CMR also revealed reduced LV dilatation with anti-CD14-treatment compared to control groups (76±5 vs 102±8 and 107±7 µl EDV in saline- and isotype-treated controls, respectively, p<0.05). Parasternal long axis echocardiography at 28 days post-STEMI confirmed that anti-CD14 antibody treatment was associated with greater LV systolic function compared to saline and isotype controls (30±1 vs 24±1 and 25±2 % EF, respectively, p<0.05; Figure 1B). Preservation of LV end-diastolic (86±4 vs 111±6 and 101±5 µl, p<0.01) and end-systolic (61±3 vs 84±5 and 77±5 µl, p<0.01) volumes was also observed with anti-CD14 treatment. Global longitudinal strain (GLS) of the LV was also significantly greater at 28 days post-STEMI with anti-CD14 treatment relative to saline and isotype controls (-8.5±0.4 vs -6.8±0.3 and -6.6±0.4 %, respectively, p<0.05). Conclusion(s) The findings of this fully blinded and randomised preclinical study provide evidence of a clinically practicable strategy of CD14 blockade initiated at reperfusion to mitigate progressive LV systolic dysfunction and dilatation post-STEMI.Figure 1.Functional outcome measures

Where AIRE we now? Where AIRE we going?

The purpose of the review is to describe the most recent advancement in understanding of the pivotal role of autoimmune regulator ( AIRE ) gene expression in central and peripheral tolerance, and the implications of its impairment in the genetic and pathogenesis of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) manifestations with insight into possible treatment options. AIRE gene expression has an important role of central and peripheral tolerance. Different AIRE gene mutations cause APECED, whereas polymorphisms and some variants may be implicated in development of other more frequently autoimmune diseases. Impaired negative T cell selection, reduction of T regulatory function, altered germinal center response, activated B cells and production of autoantibodies explain the development of autoimmunity in APECED. Recent data suggest that an excessive interferon-γ response may be the primer driver of the associated organ damage. Therefore, Janus kinase (JAK)-inhibitors may be promising therapies for treatment of broad spectrum of manifestations. AIRE has a pivotal role in immune tolerance. Disruption of this delicate equilibrium results in complex immune perturbation, ranging from severe autoimmunity, like APECED, to more common organ-specific disorders. Therefore, a deeper understanding of the correlation between AIRE function and clinical phenotype is warranted given the potential translational implication in clinical practice.

Integrative Human Genetic and Cellular Analysis of the Pathophysiological Roles of AnxA2 in Alzheimer's Disease.

Alzheimer's disease (AD) is an intractable and progressive neurodegenerative disease. Amyloid beta (Aβ) aggregation is the hallmark of AD. Aβ induces neurotoxicity through a variety of mechanisms, including interacting with membrane receptors to alter downstream signaling, damaging cellular or organelle membranes, interfering with protein degradation and synthesis, and inducing an excessive immune-inflammatory response, all of which lead to neuronal death and other pathological changes associated with AD. In this study, we extracted gene expression profiles from the GSE5281 and GSE97760 microarray datasets in the GEO (Gene Expression Omnibus) database, as well as from the Human Gene Database. We identified differentially expressed genes in the brain tissues of AD patients and healthy persons. Through GO, KEGG, and ROC analyses, annexin A2 (AnxA2) was identified as a putative target gene. Notably, accumulating evidence suggests that intracellular AnxA2 is a key regulator in various biological processes, including endocytosis, transmembrane transport, neuroinflammation, and apoptosis. Thus, we conducted a series of cell biology experiments to explore the biological function of AnxA2 in AD. The results indicate that AnxA2 gene knockdown primarily affects oxidative phosphorylation, cell cycle, AD, protein processing in the endoplasmic reticulum, SNARE interactions in vesicular transport, and autophagy. In SH-SY5Y cells secreting Aβ42, AnxA2 gene knockdown exacerbated Aβ42-induced cytotoxicity, including cell death, intracellular ROS levels, and neuronal senescence, altered cell cycle, and reduced ATP levels, suggesting its critical role in mitochondrial function maintenance. AnxA2 gene knockdown also exacerbated the inhibitory effect of Aβ42 on cell migration. AnxA2 overexpression reduced the inflammatory response induced by Aβ42, while its absence increased pro-inflammatory and decreased anti-inflammatory responses. Furthermore, AnxA2 gene knockdown facilitated apoptosis and decreased autophagy. These results indicated potential pathophysiological roles of AnxA2 in AD.

Polyphenol-mediated redox-active hydrogel with H2S gaseous-bioelectric coupling for periodontal bone healing in diabetes.

Excessive oxidative response, unbalanced immunomodulation, and impaired mesenchymal stem cell function in periodontitis in diabetes makes it a great challenge to achieve integrated periodontal tissue regeneration. Here, a polyphenol-mediated redox-active algin/gelatin hydrogel encapsulating a conductive poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber network and a hydrogen sulfide sustained-release system utilizing bovine serum albumin nanoparticles is developed. This hydrogel is found to reverse the hyperglycemic inflammatory microenvironment and enhance functional tissue regeneration in diabeticperiodontitis. Polydopamine confers the hydrogel with anti-oxidative and anti-inflammatory activity. Theslow, sustained release of hydrogen sulfide from the bovine serum albumin nanoparticles recruits mesenchymal stem cells and promotes subsequent angiogenesis and osteogenesis. Moreover, poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber confers the hydrogel with good conductivity, which enables it to transmit endogenous bioelectricity, promote cell arrangement, and increase the inflow of calcium ion. In addition, the synergistic effects of hydrogen sulfide gaseous-bioelectric coupling promotes bone formation by amplifying autophagy in periodontal ligament stem cells and modulating macrophage polarization via lipid metabolism regulation. This study provides innovative insights into the synergistic effects of conductivity, reactive oxygen species scavenging, and hydrogen sulfide on the periodontium in a hyperglycemic inflammatory microenvironment, offering a strategy for the design of gaseous-bioelectric biomaterials to promote functional tissue regeneration in immune-related diseases.

Zinc deficiency impairs the development of human regulatory B cells from purified B cells

Zinc is a vital trace element, important for many different immune processes and adequate functionality. B cell development is known to be dependent on sufficient zinc supply. Recently a regulatory B cell (Breg) population has been identified, as CD19+IL-10+ B cells, able to regulate immune responses by secretion of anti-inflammatory cytokines, such as IL-10. Due to their promotion of an anti-inflammatory milieu, Bregs could reduce or might even prevent excessive pro-inflammatory responses. Hence, having and maintaining Bregs could be interesting for patients suffering from allergies, asthma, and autoimmune diseases. Therefore, understanding Breg generation, required signaling, and their developmental requirements are important. Since our group could previously show that zinc is important for regulatory T cells, we aimed to determine the effect of zinc deficiency on Breg development from human peripheral blood CD19+ B cells. We observed highest Breg generation with a combined stimulus of CD40L and the toll like receptor (TLR) ligand, CpG-ODN2006. Using this stimulus, we observed that zinc deficient medium significantly decreased Breg generation from purified B cells. This was not seen in Bregs generated from peripheral blood mononuclear cells (PBMCs) without B cell enrichment suggesting a compensatory mechanism. In line with literature, our data also confirms Bregs develop from CD19+ B cells, since total CD19+ frequencies remained unchanged, while Breg frequencies varied between stimuli and zinc media conditions. Our study shows for the first time that zinc deficiency significantly impairs Breg development, which provides an important new perspective for clinical applications and therapeutic strategies.

Method for Predicting Environmental Vibration Impact of Existing Subway Lines and Its Practical Application

To predict accurately the impact of track vibrations caused by subway trains on adjacent buildings and address the problem of their excessive dynamic response, a method for predicting the environmental vibration impact of existing subway lines is proposed in this paper. A coupled numerical dynamical model of the train/track/tunnel system is established using the multi-scale method. Using field-measured soil vibration data, empirical formulas for soil frequency and material damping coefficient are calibrated. By combining the numerical model and the empirical formulas, buildings’ indoor vibrations and noise level can be assessed. At the same time, a solution to the problem of excessive vibration of buildings along a subway line is also proposed that optimizes the track fastener parameters. Field tests verified the accuracy of the prediction method and the effectiveness of the optimized track parameters. These research results provide a reference for predicting the vibration of buildings along subway lines and using the proposed preventive solutions.

Synergistic Phytochemical and Pharmacological Actions of Hair RiseTM Microemulsion: A Novel Herbal Formulation for Androgenetic Alopecia and Hair Growth Stimulation.

Androgenetic alopecia (AGA) is a genetic condition characterized by an excessive response to androgens, leading to hairline regression in men and hair thinning at the vertex in women, which can negatively impact self-esteem. Conventional synthetic treatments for AGA are often limited by their side effects. In contrast, Thai medicinal plants offer a promising alternative with fewer adverse effects. This study investigates the synergistic phytochemical and pharmacological effects of a novel Hair RiseTM microemulsion, formulated with bioactive extracts from rice bran (Oryza sativa), shallot bulb (Allium ascalonicum), licorice root (Glycyrrhiza glabra), and corn kernels (Zea mays), for the treatment of hair loss. The microemulsion, in concentrations of 50%, 75%, and 100% (v/v), significantly enhanced the proliferation of human hair follicle dermal papilla cells (HFDPCs) compared to minoxidil. Additionally, it upregulated critical hair growth signaling pathways, including Wnt/β-catenin (CTNNB1), Sonic Hedgehog (SHH, SMO, GLI1), and vascular endothelial growth factor (VEGF), surpassing standard controls such as minoxidil and purmorphamine. The microemulsion also demonstrated potent anti-inflammatory and antioxidant properties by reducing nitric oxide production and oxidative stress, factors that contribute to inflammation and follicular damage in AGA. Furthermore, Hair RiseTM inhibited 5α-reductase (types 1-3), a key enzyme involved in androgen metabolism, in both human prostate cancer cells (DU-145) and HFDPCs. These findings suggest that Hair RiseTM microemulsion presents a promising natural therapy for promoting hair growth and reducing hair loss via multiple synergistic mechanisms, offering a potent, plant-based alternative to synthetic treatments.

8202 Retrospective Analysis of Mixed-Meal Testing in People with Suspected Spontaneous Post-Prandial Hypoglycemia

Abstract Disclosure: N. Sankaran: None. R. Jalleh: None. C. Bischoff: None. C. Marathe: None. Introduction: While there is no consensus on the optimal confirmatory test for postprandial hypoglycemia, guidelines suggest evaluation with a mixed meal test that is most likely to provoke symptoms of hypoglycemia as nominated by the patient. However, studies evaluating post-bariatric surgery hypoglycemia indicate that meals with a lower carbohydrate content are less likely to be associated with postprandial hypoglycemia. It is hypothesized that a greater carbohydrate load may result in an excessive second-phase insulin response resulting in hypoglycemia. We evaluated the outcomes of consecutive mixed meal tests in individuals with suspected spontaneous postprandial hypoglycemia and the relationship with the percentage carbohydrate content of the test meal. Methods: We retrospectively analysed the data of 103 unselected patients who were referred to undergo a 5-hour mixed meal test following an overnight fast, between the years 2010 - 2023 at the Royal Adelaide Hospital. Correlations were determined using a linear regression model and Student’s t-test was used to compare the mean carbohydrate meal content in those with and without postprandial hypoglycemia. Outcomes: Outcomes that were measured included post-meal blood glucose, plasma insulin, plasma C-peptide levels and the macronutrient composition of the meal. Subjective reporting of symptoms during the test were also noted and correlated with the symptoms included in the Edinburgh Hypoglycemia Score. Results: 33/103 participants were excluded as they had previously undergone islet cell transplant or bariatric surgery. Out of the remaining 70 participants referred for confirmatory MMT testing, 51 were female and 19 were male. The ages of the participants ranged from 16 to 74, with the median age of 40 years. 9 participants (6 females and 3 males) had abnormal results with glucose below 3.0mmol/L. 34 participants experienced hypoglycemia with glucose levels recorded below 4.0mmol/L during the test. There was no difference in carbohydrate content consumed (61.1g, P=0.30) or percentage carbohydrate (64.5%, P=0.17) in the group without postprandial hypoglycemia compared with those with postprandial hypoglycemia (carbohydrate content 67.9 g, 69.6% carbohydrate). No correlation could be identified between the percentage of carbohydrate content of the meal with the glucose nadir (P=0.75), peak insulin concentration (P=0.99) or peak C-peptide concentration (P=0.40). The percentage of carbohydrate content of the meal was neither associated with hypoglycemia (P=0.17) or symptoms (P=0.41). Conclusion: On mixed meal testing, postprandial symptoms and hypoglycemia does not correlate with either carbohydrate load or the percentage carbohydrate content of the nominated meal. Presentation: 6/1/2024

Giant Lobular Fibrous Epulis- A Case Report

The Fibrous epulis, is a tumour like lesion arising from the gingiva, periosteum or periodontal ligament and is commonly involving the interdental papilla. Its etiology is attributed to a reactive mechanism in response to chronic irritation or tissue injury which stimulates excessive tissue response. They are usually asymptomatic and have a very slow rate of growth. The recurrence rate is high and they are commonly treated by a combination of surgical excision, thorough curettage and oral prophylaxis. We report a case of a Giant lobular fibrous epulis in a 62 year old female which was located in the left maxillary canine, first premolar region since 6 months. It was asymptomatic and was pale pink in colour and pedunculated and lobular with no involvement of the underlying bone. It was surgically excised along with thorough curettage and oral prophylaxis. The histopathology report was suggestive of fibrous epulis.

Evaluating the Prevalence of Migraine Headache among Patients with Female-Pattern Baldness

Background: According to WHO, migraine is a neurological disorder that has ranked third among the most prevalent medical conditions. Androgenetic alopecia (AGA), on the other hand, is a patterned hair loss disorder due to excessive response to androgens, affecting about half of the world's population. This disorder is presented by progressive hair loss in males and females after puberty, and sex hormones influence both diseases. Methods: A total of 50 women with clinically diagnosed AGA and a mean age of 37.5 referring to dermatology outpatient clinics of Shiraz University of Medical Sciences during 2020 were included in this study. The control group consisted of 50 women of similar age without alopecia. Hair loss was evaluated using the Ludwig classification, and the Persian versions of migraine screen questionnaire (MS_Q) and migraine disability assessment tests (MIDAS) were used to assess migraine among participants. Pain intensity was also measured using the Visual Analog scale (VAS). Results: According to the MS_Q Questionnaire, seven females (14%) in the case group and six females (12%) in the control group had migraines, and no significant correlation was observed between migraine and AGA (P = 0.766). There was no significant correlation between Ludwig score and migraine disability score in the case group with migraine (Spearman correlation coefficient = 0.367, P = 0.419). The only significant positive correlation was between Ludwig score and visual analog scale (VAS) in the case group with migraine (Spearman correlation coefficient = 0.844, P = 0.017) Conclusions: Based on the results, no significant correlation was found between migraine and androgenetic alopecia.

Tissue Kallikrein-1 Suppresses Type I Interferon Responses and Reduces Depressive-Like Behavior in the MRL/lpr Lupus-Prone Mouse Model.

Excessive production and response to Type I interferons (IFNs) is a hallmark of systemic lupus erythematosus (SLE). Neuropsychiatric lupus (NPSLE) is a common manifestation of human SLE, with major depression as the most common presentation. Clinical studies have demonstrated that IFNα can cause depressive symptoms. We have shown that the kallikrein-kinin system (KKS) [comprised of kallikreins (Klks) and bradykinins] and angiotensin-converting enzyme inhibitors suppressed Type I IFN responses in dendritic cells from lupus-prone mice and human peripheral blood mononuclear cells. Tissue Klk genes are decreased in patients with lupus, and giving exogenous Klk1 ameliorated kidney pathology in mice. We retro-orbitally administered mouse klk1 gene-carrying adenovirus in the Murphy Roths Large lymphoproliferative (MRL/lpr) lupus-prone mice at early disease onset and analyzed immune responses and depressive-like behavior. Klk1 improved depressive-like behavior, suppressed interferon-responsive genes and neuroinflammation, and reduced plasma IFNα levels and proinflammatory cytokines. Klk1 also reduced IFNAR1 and JAK1 protein expression, important upstream molecules in Type I IFN signaling. Klk1 reduced bradykinin B1 receptor expression, which is known to induce proinflammatory response. Together, these findings suggest that Klk1 may be a potential therapeutic candidate to control IFNα production/responses and other inflammatory responses in SLE and NPSLE.

Immune-Mediated Inflammatory Diseases and Cancer - a dangerous liaison.

Patients with Immune-Mediated Inflammatory Diseases (IMIDs) are known to have an elevated risk of developing cancer, but the exact causative factors remain subject to ongoing debate. This narrative review aims to present the available evidence concerning the intricate relationship between these two conditions. Environmental influences and genetic predisposition lead to a dysregulated immune response resulting in chronic inflammation, which is crucial in the pathogenesis of IMIDs and oncogenic processes. Mechanisms such as the inflammatory microenvironment, aberrant intercellular communication due to abnormal cytokine levels, excessive reparative responses, and pathological angiogenesis are involved. The chronic immunosuppression resulting from IMIDs treatments further adds to the complexity of the pathogenic scenario. In conclusion, this review highlights critical gaps in the current literature, suggesting potential avenues for future research. The intricate interplay between IMIDs and cancer necessitates more investigation to deepen our understanding and improve patient management.