Search results for: pathophysiology
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 81

Search results for: pathophysiology

51 Dopamine and Female Sexual Function: A Clinical and Biochemical Study

Authors: Azza Gaber Antar Farag, Eman Abd El Fatah Badr, Wesam Ahmed Tawfik Hasssan Abdel Aal, Mustafa Elsayed Elshaib

Abstract:

Background: Female Sexual Dysfunction (FSD) represents recurrent and persistent problems that distress women and/or strain their relationships with their partners. Dopamine can affect sexual function and interacts with ovarian hormones in the ventromedial area in the hypothalamus. Objective: To investigate the possible role of dopamine in FSD. Method: This prospective case-control study was carried on 100 women having FSD and 100 healthy volunteer females. They were recruited from the Al-Menoufia governorate. All included women were subjected to the questionnaire to assess their demographic and gynecological data as well as sexual function. They were investigated for serum levels of dopamine, estradiol, progesterone and DHEA hormones. Results: Dopamine serum levels were significantly lower in females having sexual dysfunction (6.68±4.14) than controls (57.97±26.26) (P>0.001). This decreased dopamine level was of a significant positive correlation with the arousal domain and significant negative correlation regarding the pain domain (r=-0.19, p=0.01). Also, estradiol serum levels were significantly lower (P>0.001), but progesterone and DHEA serum levels were significantly higher in the FSD group than controls (P>0.001). There was a significant negative correlation between dopamine and DHEA serum levels (r= -0.45, p <0.001). Conclusions: Decreased dopamine serum levels may have an active role in the pathophysiology of FSD, impacting mainly arousal and pain domains, and its targeting should be considered during FSD management.

Keywords: dopamine, estradiol, progesterone, DHEA, females sexual dysfunction

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50 Decision-Making Under Uncertainty in Obsessive-Compulsive Disorder

Authors: Helen Pushkarskaya, David Tolin, Lital Ruderman, Ariel Kirshenbaum, J. MacLaren Kelly, Christopher Pittenger, Ifat Levy

Abstract:

Obsessive-Compulsive Disorder (OCD) produces profound morbidity. Difficulties with decision making and intolerance of uncertainty are prominent clinical features of OCD. The nature and etiology of these deficits are poorly understood. We used a well-validated choice task, grounded in behavioral economic theory, to investigate differences in valuation and value-based choice during decision making under uncertainty in 20 unmedicated participants with OCD and 20 matched healthy controls. Participants’ choices were used to assess individual decision-making characteristics. Compared to controls, individuals with OCD were less consistent in their choices and less able to identify options that were unambiguously preferable. These differences correlated with symptom severity. OCD participants did not differ from controls in how they valued uncertain options when outcome probabilities were known (risk) but were more likely than controls to avoid uncertain options when these probabilities were imprecisely specified (ambiguity). These results suggest that the underlying neural mechanisms of valuation and value-based choices during decision-making are abnormal in OCD. Individuals with OCD show elevated intolerance of uncertainty, but only when outcome probabilities are themselves uncertain. Future research focused on the neural valuation network, which is implicated in value-based computations, may provide new neurocognitive insights into the pathophysiology of OCD. Deficits in decision-making processes may represent a target for therapeutic intervention.

Keywords: obsessive compulsive disorder, decision-making, uncertainty intolerance, risk aversion, ambiguity aversion, valuation

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49 Comparison of Central Light Reflex Width-to-Retinal Vessel Diameter Ratio between Glaucoma and Normal Eyes by Using Edge Detection Technique

Authors: P. Siriarchawatana, K. Leungchavaphongse, N. Covavisaruch, K. Rojananuangnit, P. Boondaeng, N. Panyayingyong

Abstract:

Glaucoma is a disease that causes visual loss in adults. Glaucoma causes damage to the optic nerve and its overall pathophysiology is still not fully understood. Vasculopathy may be one of the possible causes of nerve damage. Photographic imaging of retinal vessels by fundus camera during eye examination may complement clinical management. This paper presents an innovation for measuring central light reflex width-to-retinal vessel diameter ratio (CRR) from digital retinal photographs. Using our edge detection technique, CRRs from glaucoma and normal eyes were compared to examine differences and associations. CRRs were evaluated on fundus photographs of participants from Mettapracharak (Wat Raikhing) Hospital in Nakhon Pathom, Thailand. Fifty-five photographs from normal eyes and twenty-one photographs from glaucoma eyes were included. Participants with hypertension were excluded. In each photograph, CRRs from four retinal vessels, including arteries and veins in the inferotemporal and superotemporal regions, were quantified using edge detection technique. From our finding, mean CRRs of all four retinal arteries and veins were significantly higher in persons with glaucoma than in those without glaucoma (0.34 vs. 0.32, p < 0.05 for inferotemporal vein, 0.33 vs. 0.30, p < 0.01 for inferotemporal artery, 0.34 vs. 0.31, p < 0.01 for superotemporal vein, and 0.33 vs. 0.30, p < 0.05 for superotemporal artery). From these results, an increase in CRRs of retinal vessels, as quantitatively measured from fundus photographs, could be associated with glaucoma.

Keywords: glaucoma, retinal vessel, central light reflex, image processing, fundus photograph, edge detection

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48 Polycystic Ovary Syndrome - Clinical Profile of Women Attending NPFDB Subfertility Clinic

Authors: Komathy Thiagarajan, Mohd. Azizuddin Mohd. Yussof, Hasnoorina Husin, Noor Azreena Abd Aziz, Faezah Shekh Abdullah, Abdul Wahaf Abdul Wahid

Abstract:

Polycystic Ovary Syndrome (PCOS) presents with a plethora of clinical features owing to the multifaceted underlying pathophysiology. This study was conducted to determine the clinical features unique to the sub fertile women attending the Sub fertility Clinic of the National Population and Family Development Board (NPFDB) so that a more holistic approach can be adopted to further enhance the pregnancy outcome in those women. This was a case-control study conducted over a span of three years (from January 2014 until December 2016), whereby women who fulfilled the Rotterdam Criteria 2004 were classified as PCOS (n=79) and women who did not fulfill the Rotterdam Criteria were classified as controls (n=88). The mean age of the women was 30.1 years and the mean duration of marriage was 3.93 years. The majority of women suffered from primary sub fertility (82.6%). The median age was lower among PCOS women (29.0 years) compared to the controls (30.0 years), p<0.05. The majority of PCOS women (43.0%) were obese (BMI > 30 kg/m2) compared to only 19.3% who were obese in the control group, p<0.05. Hypertension was present in 59.5% of PCOS women and only in 36.4% of the control group, p<0.05. There were significantly more women who presented with hirsutism in PCOS group (27.8%) as compared to the control group (5.7%), p<0.05. The findings of this study elucidate that the clinical features of significance among sub fertile women suffering from PCOS, if detected early, are amenable to lifestyle modifications and timely interventions can potentially improve the fertility outcomes in this group of women.

Keywords: clinical features, fertility, lifestyle modification, PCOS

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47 The Association among Obesity, Lipid Profiles and Depression Severity in Patients with Depressive Disorder

Authors: In Hee Shim, Dong Sik Bae

Abstract:

Introduction: Obesity and unfavorable lipid profile may be linked to depressive disorders. This study compared the levels of obesity, lipid profiles and depression severity of patients with depressive disorders. Methods: This study included 156 patients diagnosed with a depressive disorder who were hospitalized between March 2012 and February 2016. The patients were categorized into mild to moderate and severe depressive groups, based on Hamilton Depression Rating Scale scores (Mild to moderate depression 8-23 vs. severe depression ≥ 24). The charts of the patients were reviewed to evaluate body mass index and lipid profiles, including total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TG), confounding factors, such as other general medical disorders (hypertension, diabetes mellitus, and dyslipidemia), except smoking status (insufficient data). Demographic and clinical characteristics, such as age, sex, comorbidities, family history of mood disorders, psychotic features, and prescription patterns were also assessed. Results: Compared to the mild to the moderate depressive group, patients with severe depression had significantly lower rate of male and comorbidity. The patients with severe depression had a significantly lower TG than patients in the mild to moderate depressive group. After adjustment for the sex and comorbidity, there were no significant differences between the two groups in terms of the obesity and lipid profiles, including TG. Conclusion: These results did not show a significant difference in the association between obesity, lipid profiles and the depression severity. The role of obesity and lipid profiles in the pathophysiology of depression remains to be clarified.

Keywords: depression, HAM-D, lipid profiles, obesity

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46 Possible Management of Acute Liver Failure Caused Experimentally by Thioacetamide Through a Wide Range of Nano Natural Anti-Inflammatory And Antioxidants Compounds [Herbal Approach]

Authors: Sohair Hassan, Olfat Hammam, Sahar Hussein, Wessam Magdi

Abstract:

Objective: Acute liver failure (ALF) is a clinical condition with an unclear history of pathophysiology, making it a challenging task for scientists to reverse the disease in its initial phase and to help the liver re-function customary: this study aimed to estimate the hepatoprotective effects of Punica granatum Lpeel and Pistacia atlantica leaves as a multi-rich antioxidants ingredients either in their normal and/or in their nanoforms against thioacetamide induced acute liver failure in a rodent model. Method: Male Wistar rats (n=60) were divided into six equal groups, the first group employed as a control; The second group administered a dose of 350 mg /Kg/ b.w of thioacetamide (TAA)-IP, from the third to the sixth group received TAA + [2mls / 100 g b.w/d] of aqueous extracts of Punica granatum L and Pistacia atlantica either in their normal and/or Nano forms consecutively for (14 days) Results: Recorded significant elevation in liver enzymes, lipid profiles, LPO (p= 0.05) and NO with a marked significant decrease in GSH and SOD accompanied by an elevation in inflammatory cytokine (IL6, TNF-α, and AFP) in addition to a noticeable increase in HSP70 level & degradation in DNA respectively in TAA challenged group. However significant and subsequent amelioration of most of the impaired markers was observed with ip nano treatment of both extracts. Conclusion: The current results highlighted the high performance of both plant nano extracts and their hepatoprotective impact and their possible therapeutic role in the amelioration of TAA induced acute liver failure in experimental animals.

Keywords: acute liver failure HPLC, IL6, nano extracts, thioacetamide, TNF-α

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45 An Evaluation of Neuropsychiatric Manifestations in Systemic Lupus Erythematosus Patients in Saudi Arabia and Their Associated Factors

Authors: Yousef M. Alammari, Mahmoud A. Gaddoury, Reem A. Almohaini, Sara A. Alharbi, Lena S. Alsaleem, Lujain H. Allowaihiq, Maha H. Alrashid, Abdullah H. Alghamdi, Abdullah A. Alaryni

Abstract:

Objective: The goal of this study was to establish the prevalence of neuropsychiatric symptoms in systemic lupus erythematosus (NPSLE) patients in Saudi Arabia and the variables that are linked to it. Methods: During June 2021, this cross-sectional study was carried out among SLE patients in Saudi Arabia. The Saudi Rheumatism Association exploited social media platforms to provide a self-administered online questionnaire to SLE patients. All data analyses were performed using the Statistical Packages for Social Sciences (SPSS) version 26. Results: Two hundred and five SLE patients participated in the study (females 91.3 % vs. males 8.7 %). In addition, 13.5 % of patients had a family history of SLE, and 26% had SLE for one to three years. Alteration or loss of sensation (53.4%), Fear (52.4%), and headache (48.1%) were the most prevalent signs of neuropsychiatric symptoms in systemic lupus erythematosus (NPSLE) patients. The prevalence of patients with NPSLE was 40%. In a multivariate regression model, fear, altered sensations, cerebrovascular illness, sleep disruption, and diminished interest in routine activities were identified as independent risk variables for NPSLE. Conclusion: Nearly half of SLE patients demonstrated NP manifestations, with significant symptoms including fear, alteration of sensation, cerebrovascular disease, sleep disturbance, and reduced interest in normal activities. To detect the pathophysiology of NPSLE, it is necessary to understand the relationship between neuropsychiatric morbidity and other relevant rheumatic disorders in the SLE population.

Keywords: neuropsychiatric, systemic lupus erythematosus, NPSLE, prevalence, SLE patients

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44 Tractography Analysis of the Evolutionary Origin of Schizophrenia

Authors: Asmaa Tahiri, Mouktafi Amine

Abstract:

A substantial number of traditional medical research has been put forward to managing and treating mental disorders. At the present time, to our best knowledge, it is believed that fundamental understanding of the underlying causes of the majority psychological disorders needs to be explored further to inform early diagnosis, managing symptoms and treatment. The emerging field of evolutionary psychology is a promising prospect to address the origin of mental disorders, potentially leading to more effective treatments. Schizophrenia as a topical mental disorder has been linked to the evolutionary adaptation of the human brain represented in the brain connectivity and asymmetry directly linked to humans higher brain cognition in contrast to other primates being our direct living representation of the structure and connectivity of our earliest common African ancestors. As proposed in the evolutionary psychology scientific literature the pathophysiology of schizophrenia is expressed and directly linked to altered connectivity between the Hippocampal Formation (HF) and Dorsolateral Prefrontal Cortex (DLPFC). This research paper presents the results of the use of tractography analysis using multiple open access Diffusion Weighted Imaging (DWI) datasets of healthy subjects, schizophrenia-affected subjects and primates to illustrate the relevance of the aforementioned brain regions connectivity and the underlying evolutionary changes in the human brain. Deterministic fiber tracking and streamline analysis were used to generate connectivity matrices from the DWI datasets overlaid to compute distances and highlight disconnectivity patterns in conjunction with other fiber tracking metrics; Fractional Anisotropy (FA), Mean Diffusivity (MD) and Radial Diffusivity (RD).

Keywords: tractography, evolutionary psychology, schizophrenia, brain connectivity

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43 Evaluation of Serine and Branched Chain Amino Acid Levels in Depression and the Beneficial Effects of Exercise in Rats

Authors: V. A. Doss, R. Sowndarya, K. Juila Rose Mary

Abstract:

Objective: Amino acid neurotransmitter system dysfunction plays a major role in the pathophysiology of depression. The objective of the present study was to identify the amino acids as possible metabolite biomarkers for depression using GCMS (Gas Chromatography Mass Spectrometry) before and after exercise regimen in brain samples of depression induced animal models. Methods: Depression-like behaviour was induced by Chronic Unpredictable mild stress (CUMS). Severity of depression was measured by forced swim test (FST) and sucrose consumption test (SCT). Swimming protocol was followed for 4 weeks of exercise treatment. Brain obtained from depressed and exercise treated rats were used for the metabolite analysis by GCMS. Subsequent statistical analysis obtained by ANOVA followed by post hoc test revealed significant metabolic changes. Results: Amino acids such as alanine, glycine, serine, glutamate, homocysteine, proline and branched chain aminoacids (BCAs) Leucine, Isoleucine, Valine were determined in brain samples of control, depressed and exercised groups. Among these amino acids, the levels of D-Serine and branched chain amino acids were found to be decreased in depression induced rats. After four weeks of swimming exercise regimen, there were improvements in the levels of serine and Branched chain amino acids. Conclusion: We suggest that Serine and BCAs may be investigated as potential metabolite markers using GCMS and their beneficial metabolic changes in Exercise.

Keywords: metabolomics, depression, forced swim test, exercise, amino acid metabolites, GCMS, biomarker

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42 The Effect of an Abnormal Prefrontal Cortex on the Symptoms of Attention Deficit/Hyperactivity Disorder

Authors: Irene M. Arora

Abstract:

Hypothesis: Attention Deficit Hyperactivity Disorder is the result of an underdeveloped prefrontal cortex which is the primary cause for the signs and symptoms seen as defining features of ADHD. Methods: Through ‘PubMed’, ‘Wiley’ and ‘Google Scholar’ studies published between 2011-2018 were evaluated, determining if a dysfunctional prefrontal cortex caused the characteristic symptoms associated with ADHD. The search terms "prefrontal cortex", "Attention-Deficit/Hyperactivity Disorder", "cognitive control", "frontostriatal tract" among others, were used to maximize the assortment of relevant studies. Excluded papers were systematic reviews, meta-analyses and publications published before 2010 to ensure clinical relevance. Results: Nine publications were analyzed in this review, all of which were non-randomized matched control studies. Three studies found a decrease in the functional integrity of the frontostriatal tract fibers in conjunction with four studies finding impaired frontal cortex stimulation. Prefrontal dysfunction, specifically medial and orbitofrontal areas, displayed abnormal functionality of reward processing in ADHD patients when compared to their normal counterparts. A total of 807 subjects were studied in this review, yielding that a little over half (54%) presented with remission of symptoms in adulthood. Conclusion: While the prefrontal cortex shows the highest consistency of impaired activity and thinner volumes in patients with ADHD, this is a heterogenous disorder implicating its pathophysiology to the dysfunction of other neural structures as well. However, remission of ADHD symptomatology in adulthood was found to be attributable to increased prefrontal functional connectivity and integration, suggesting a key role for the prefrontal cortex in the development of ADHD.

Keywords: prefrontal cortex, ADHD, inattentive, impulsivity, reward processing

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41 Influence of Gestational Diabetes Mellitus on the Activity of Steroid C17-Hydroxylase-C17,20-Lyase in Patients with Intrahepatic Cholestasis of Pregnancy

Authors: Leona Ondrejikova, Martin Hill, Antonin Parizek

Abstract:

The incidence of gestational diabetes mellitus (GDM) is higher in women predisposed to developing intrahepatic cholestasis of pregnancy (ICP). Both diseases are associated with altered steroidogenesis when compared with none-ICP controls. However, the effect of GDM on circulating steroids in ICP patients remains unclear. The question remains, whether the levels of circulating steroids differ between ICP patients with and without GDM. In total 10 ICP patients without GDM (ICP+GDM-), 7 ICP patients with GDM (ICP+GDM+), and 15 controls (ICP-GDM-) were monitored during late gestation, at labor, and during three periods postpartum (day 5, week 3, and week 6 postpartum) (Šimják et al., 2018). The relationships between steroid profiles and patients’ status were evaluated using the ANOVA model consisting of subject factor, between-subject factors Group (ICP+GDM+, ICP+GDM-, ICP-GDM-), gestational age at the diagnosis of ICP and gestational age at labor, and within-subject factor Stage and ICP × Stage interaction. The levels of the C21 and C19 Δ5 steroids and 5α/β-reduced C19 steroids were highest in ICP+GDM+, while those for the ICP-GDM-, and ICP+GDM- groups were lower. In the C21 Δ4 steroids and their 5α/β-reduced metabolites, the steroid levels were highest in the ICP+GDM-, intermediate in the ICP-GDM- and lowest in the ICP+GDM+ group. This higher concentration in ICP+GDM- group may be of importance as the 5α-pregnane-3α,20α-diol disulfate, is considered as the substance inducing ICP. In general, these data show that the comorbidity with GDM substantially changes the steroidome in ICP patients towards the higher activity of steroid CYP17A1 lyase step in adrenal zona reticularis reduced CYP17A1 hydroxylase step in zona fasciculata. This is consistent with our previously published hypothesis about the critical role of maternal zona reticularis in the pathophysiology of ICP. Our present data also indicate that the comorbidity with GDM might moderate the gravity of the ICP in this way.

Keywords: CYP17A1, GC-MS, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy

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40 Possible Mechanism of DM2 Development in OSA Patients Mediated via Rev-Erb-Alpha and NPAS2 Proteins

Authors: Filip Franciszek Karuga, Szymon Turkiewicz, Marta Ditmer, Marcin Sochal, Piotr Białasiewicz, Agata Gabryelska

Abstract:

Circadian rhythm, an internal coordinator of physiological processes is composed of a set of semi-autonomous clocks. Clocks are regulated through the expression of circadian clock genes which form feedback loops, creating an oscillator. The primary loop consists of activators: CLOCK, BMAL1 and repressors: CRY, PER. CLOCK can be substituted by the Neuronal PAS Domain Protein 2 (NPAS2). Orphan nuclear receptor (REV-ERB-α) is a component of the secondary major loop, modulating the expression of BMAL1. Circadian clocks might be disrupted by the obstructive sleep apnea (OSA), which has also been associated with type II diabetes mellitus (DM2). Interestingly, studies suggest that dysregulation of NPAS2 and REV-ERB-α might contribute to the pathophysiology of DM2 as well. The goal of our study was to examine the role of NPAS2 and REV-ERB-α in DM2 in OSA patients. After examination of the clinical data, all participants underwent polysomnography (PSG) to assess their apnea-hypopnea index (AHI). Based on the acquired data participants were assigned to one of 3 groups: OSA (AHI>30, no DM2; n=17 for NPAS2 and 34 for REV-ERB-α), DM2 (AHI>30 + DM2; n=7 for NPAS2 and 15 for REV-ERB-α) and control group (AHI<5, no DM2; n=16 for NPAS2 and 31 for REV-ERB-α). ELISA immunoassay was performed to assess the serum protein level of REV-ERB-α and NPAS2. The only statistically significant difference between groups was observed in NPAS2 protein level (p=0.037). Post-hoc analysis showed significant differences between the OSA and the control group (p=0.017). AHI and NPAS2 level was significantly correlated (r=-0.478, p=0.002) in all groups. A significant correlation was observed between the REV-ERB-α level and sleep efficiency (r=0.617, p=0.005) as well as sleep maintenance efficiency (r=0.645, p=0.003) in the OSA group. We conclude, that NPAS2 is associated with OSA severity and might contribute to metabolic sequelae of this disease. REV-ERB-α on the other hand can influence sleep continuity and efficiency.

Keywords: OSA, diabetes mellitus, endocrinology, chronobiology

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39 Pistachio Supplementation Ameliorates the Motor and Cognitive Deficits in Rotenone-Induced Rat Model of Parkinson’s Disease

Authors: Saida Haider, Syeda Madiha

Abstract:

Parkinson’s disease (PD) is a common neurological disorder characterized by motor deficits and loss of dopaminergic neurons. Oxidative stress is said to play a pivotal role in the pathophysiology of the disease. In the present study, PD was induced by injection of rotenone (1.5 mg/kg/day, s.c.) for eight days. Pistachio (800 mg/kg/day, p.o.) was given for two weeks. At the end of treatment brains were dissected out and striatum was isolated for biochemical and neurochemical analysis. Morris water maze (MWM) test and novel object recognition (NOR) task was used to test the memory function while motor behavior was determined by open field test (OFT), Kondziela inverted screen test (KIST), pole test (PT), beam walking test (BWT), inclined plane test (IPT) and footprint (FP) test. Several dietary components have been evaluated as potential therapeutic compounds in many neurodegenerative diseases. Increasing evidence shows that nuts have protective effects against various diseases by improving the oxidative status and reducing lipid peroxidation. Pistachio is the only nut that contains anthocyanin, a potent antioxidant having neuroprotective properties. Results showed that pistachio supplementation significantly restored the rotenone-induced motor deficits and improved the memory performance. Moreover, rats treated with pistachio also exhibited enhanced oxidative status and increased dopamine (DA) and 5-hydroxytryptamine (5-HT) concentration in striatum. In conclusion, to our best knowledge, we have for the first time shown that pistachio nut possesses neuroprotective effects against rotenone-induced motor and cognitive deficits. These beneficial effects of pistachio may be attributed to its high content of natural antioxidant and phenolic compounds. Hence, consumption of pistachio regularly as part of a daily diet can be beneficial in the prevention and treatment of PD.

Keywords: rotenone, pistachio, oxidative stress, Parkinson’s disease

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38 Vital Pulp Therapy: The Minimally Invasive Endodontic Therapy for Mature Permanent Teeth

Authors: Fadwa Chtioui

Abstract:

Vital Pulp Therapy (VPT) is nowadays challenging the deep-rooted dogma of root canal treatment, being the only therapeutic option for permanent teeth diagnosed with irreversible pulpitis or carious pulp exposure. Histologic and clinical research has shown that compromised dental pulp can be treated without the full removal or excavation of all healthy pulp, and the outcome of the partial or full pulpotomy followed by a Tricalcium-Silicate-based dressing seems to show promising results in maintaining pulp vitality and preserving affected teeth in the long term. By reviewing recent advances in the techniques of VPT and their clinical effectiveness and safety in permanent teeth with irreversible Pulpitis, this work provides a new understanding of pulp pathophysiology and defense mechanisms and will reform dental practitioners' decision-making in treating irreversible pulpits from root canal therapy to vital pulp therapy by taking advantage of the biological effects of Tricalcium Silicate materials. Biography of presenting author: Fadwa Chitoui graduated from the school of Dental Medicine of Monastir, Tunisia, in 2015. After getting her DDS degree with honors, she earned her Postgraduate master's Degree in Endodontics and Restorative Dentistry from her Faculty. Since 2021, she has Started her own private and specialized practice based in the capital Tunis. She enjoys the sphere of associative life, worked with national and international associations, and got engaged in scientific dental research, whereby she tailored her passion for her field of specialty towards broadening her knowledge and ambitions, holding conferences and workshops nationally and internationally and publishing scientific articles in several journals.

Keywords: irreversible pulpitis, permanenet teeth, vital pulp therapy, pulpotomy

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37 Nanoparticle Induced Neurotoxicity Mediated by Mitochondria

Authors: Nandini Nalika, Suhel Parvez

Abstract:

Nanotechnology has emerged to play a vital role in developing all through the industrial world with an immense production of nanomaterials including nanoparticles (NPs). Many toxicological studies have confirmed that due to unique small size and physico-chemical properties of NPs (1-100nm), they can be potentially hazardous. Metallic NPs of small size have been shown to induce higher levels of cellular oxidative stress and can easily pass through the Blood Brain Barrier (BBB) and significantly accumulate in brain. With the wide applications of titanium dioxide nanoparticles (TNPs) in day-to-day life in form of cosmetics, paints, sterilisation and so on, there is growing concern regarding the deleterious effects of TNPs on central nervous system and mitochondria appear to be important cellular organelles targeted to the pro-oxidative effects of NPs and an important source that contribute significantly for the production of reactive oxygen species after some toxicity or an injury. The aim of our study was to elucidate the effect of TNPs in anatase form with different concentrations (5-50 µg/ml) following with various oxidative stress markers in isolated brain mitochondria as an in vitro model. Oxidative stress was determined by measuring the different oxidative stress markers like lipid peroxidation as well as the protein carbonyl content which was found to be significantly increased. Reduced glutathione content and major glutathione metabolizing enzymes were also modulated signifying the role of glutathione redox cycle in the pathophysiology of TNPs. The study also includes the mitochondrial enzymes (Complex 1, Complex II, complex IV, Complex V ) and the enzymes showed toxicity in a relatively short time due to the effect of TNPs. The study provide a range of concentration that were toxic to the neuronal cells and data pointing to a general toxicity in brain mitochondria by TNPs, therefore, it is in need to consider the proper utilization of NPs in the environment.

Keywords: mitochondria, nanoparticles, brain, in vitro

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36 Serum Interlukin-8 and Immunomodulation in Beta Thalassemia Patients

Authors: Shahira El Shafie, Hanaa Eldash, Engy Ghabbour, Mohamed Eid

Abstract:

Several immunologic defects can be found in patients with beta-thalassemia, among which the impairment of neutrophil phagocytic function is of utmost importance. Attention has been directed to the role of proinflammatory cytokines in neutrophil chemotaxis and phagocytosis. Interleukin-8 (IL-8) is an important chemotactic and activation peptide for neutrophils; changes in IL-8 level and potential correlation with neutrophil function can be relevant to immunomodulation pathophysiology in beta-thalassemia patients. This case-control study aimed to evaluate IL-8 level and to assess granulocyte recruitment, as markers of immunomodulation, in poly-transfused thalassemia patients attending Fayoum University Hospitals. The study was conducted on 50 patients with ß thalassemia and 32 age-matched controls. 21/50 patients were transfused more than ten times, and 29/50 were transfused in a lower frequency. Patients and controls were subjected to thorough history taking and clinical examination, measurement of IL-8 level using human IL-8 ELISA kit, and Rebuck skin window technique (RSWT) to assess granulocyte recruitment. Our data showed statistically significant higher levels of IL-8 in ß thalassemia patients compared to control with a much higher difference in patients transfused more than ten times. Neutrophil recruitment was significantly lower in ß thalassemia patients compared to control at 4 hours and 24 hours test time. Although IL-8, the main chemotactic pro-inflammatory cytokine showed a higher level in thalassemia patients, neutrophils recruitment was significantly lower, especially in those receiving more than ten transfusion times. Our findings suggest a possible role of other neutrophil chemotactic factors, defective neutrophil response, or increased IL-8 as compensation of abnormal function. We recommend the use of IL-8 and Rebuck skin window technique as useful markers of immunomodulation in thalassemia and further study for these biomarkers to assess their clinical implications and impact on the management of thalassemia patients.

Keywords: beta-thalassemia, Interleukin-8, Rebuck skin window technique, immunomodulation

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35 Postural Balance And Falls Risk In Persons With Multiple Sclerosis: Effect Of Gender Differences

Authors: Sonda Jallouli, Sameh Ghroubi, Salma Sakka, Abdelmoneem Yahia, Mohamed Habib Elleuch, Imen Ben Dhia, Chokri Mhiri, Omar Hammouda

Abstract:

The pathophysiology, prevalence, and progression of MS are gender dependent. Indeed, the inflammation is more pronounced in women, but the neurodegeneration is more important in men. In addition, women have more sleep disorders while men suffer more from cognitive decline. These non-physical disorders can negatively affect postural balance and fall risk. However, no study has examined the difference between men and women in those physical parameters in MS. Our objective was to determine the effect gender difference on postural balance and fall risk in MS persons. Methods: Eight men and twelve women with relapsing remitting-MS participated in this study. The assessment includes a posturographic examination to assess static (with eyes opened (EO) and eyes closed (EC)) and dynamic (with EO) postural balance. Unipedal balance and fall risk were assessed by a clinical unipedal balance test and the Four Square Step Test, respectively. Sleep quality was assessed using Spiegel's questionnaire, and cognitive assessment was performed using the Montreal Cognitive Assessment (MoCA) and the Simple Reaction Time Test. Results: Compared to men, women showed an increase in CdPVm in static bipedal condition with EC (p=0.037; d=0.71) and a decrease in MoCA scores (p=0.028; d=1.06). No gender differences were found in the other tests. Discussion: Static postural balance was more impaired in women compared to men. This result could be explained by the more pronounced cognitive decline observed in women compared to men. Indeed, cognitive disorders have been shown to be predictive factors of postural balance impairment. Conclusion: women were less stable than men in the static condition, possibly due to their lower cognitive performance. This gender difference could be taken into account by therapists in training programs.

Keywords: multiple sclerosis, bipedal postural balance, fall risk, sleep disturbance, cognitive deficiency

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34 Ethanol in Carbon Monoxide Intoxication: Focus on Delayed Neuropsychological Sequelae

Authors: Hyuk-Hoon Kim, Young Gi Min

Abstract:

Background: In carbon monoxide (CO) intoxication, the pathophysiology of delayed neurological sequelae (DNS) is very complex and remains poorly understood. And predicting whether patients who exhibit resolved acute symptoms have escaped or will experience DNS represents a very important clinical issue. Brain magnetic resonance (MR) imaging has been conducted to assess the severity of brain damage as an objective method to predict prognosis. And co-ingestion of a second poison in patients with intentional CO poisoning occurs in almost one-half of patients. Among patients with co-ingestions, 66% ingested ethanol. We assessed the effects of ethanol on neurologic sequelae prevalence in acute CO intoxication by means of abnormal lesion in brain MR. Method: This study was conducted retrospectively by collecting data for patients who visited an emergency medical center during a period of 5 years. The enrollment criteria were diagnosis of acute CO poisoning and the measurement of the serum ethanol level and history of taking a brain MR during admission period. Official readout data by radiologist are used to decide whether abnormal lesion is existed or not. The enrolled patients were divided into two groups: patients with abnormal lesion and without abnormal lesion in Brain MR. A standardized extraction using medical record was performed; Mann Whitney U test and logistic regression analysis were performed. Result: A total of 112 patients were enrolled, and 68 patients presented abnormal brain lesion on MR. The abnormal brain lesion group had lower serum ethanol level (mean, 20.14 vs 46.71 mg/dL) (p-value<0.001). In addition, univariate logistic regression analysis showed the serum ethanol level (OR, 0.99; 95% CI, 0.98 -1.00) was independently associated with the development of abnormal lesion in brain MR. Conclusion: Ethanol could have neuroprotective effect in acute CO intoxication by sedative effect in stressful situation and mitigative effect in neuro-inflammatory reaction.

Keywords: carbon monoxide, delayed neuropsychological sequelae, ethanol, intoxication, magnetic resonance

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33 Attenuation of Endotoxin Induced Hepatotoxicity by Dexamethasone, Melatonin and Pentoxifylline in White Albino Mice: A Comparative Study

Authors: Ammara Khan

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Sepsis is characterized by an overwhelming surge of cytokines and oxidative stress to one of many factors, gram-negative bacteria commonly implicated. Despite major expansion and elaboration of sepsis pathophysiology and therapeutic approach; death rate remains very high in septic patients due to multiple organ damages including hepatotoxicity.The present study was aimed to ascertain the adequacy of three different drugs delivered separately and collectively- low dose steroid-dexamethasone (3mg/kg i.p) ,antioxidant-melatonin(10 mg/kg i.p) ,and phosphodiesterases inhibitor - pentoxifylline (75 mg/kg i.p)in endotoxin-induced hepatotoxicity in mice. Endotoxin/lipopolysaccharides induced hepatotoxicity was reproduced in mice by giving lipopolysaccharide of serotype E.Coli intraperitoneally. The preventive role was questioned by giving the experimental agent half an hour prior to LPS injection whereas the therapeutic potential of the experimental agent was searched out via post-LPS delivering. The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with a histopathological examination of liver tissue. Dexamethasone is given before (Group 3) and after LPS (group 4) significantly attenuated LPS generated liver injury.Pentoxifylline generated similar results and serum ALT; AST histological alteration abated considerably (p≤ 0.05) both in animals subjected to pentoxifylline pre (Group 5) and post-treatment(Group 6). Melatonin was also prosperous in aversion (Group 7) and curation (Group 8) of LPS invoked hepatotoxicity as evident by lessening of augmented ALT (≤0.01) and AST (≤0.01) along with restoration of pathological changes in liver sections (p≤0.05). Combination therapies with dexamethasone in conjunction with melatonin (Group 9), dexamethasone together with pentoxifylline (Group 10), and pentoxifylline along with melatonin (Group 11) after LPS administration tapered LPS evoked hepatic dysfunction statistically considerably. In conclusion, both melatonin and pentoxifylline set up promising results in endotoxin-induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis-induced liver failure.

Keywords: endotoxin/lipopolysacchride, dexamethasone, hepatotoxicity, melatonin, pentoxifylline

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32 In vivo Activity of Pathogenic Bacteria on Natural Polyphenolic Compounds

Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, Ch. V. Rao

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Gastric ulcer is a major global health threat, and it is the leading cause of stomach cancer death worldwide. Helicobacter pylori bacteriumis the most important etiologic factor for gastric ulcer. This infection is highly pervasive in South Asian developing countries, especially in India, Nepal, Srilanka etc. due to diversification in geographic area. Pathophysiology of gastric mucosal damage associated with non-invasive bacterium has not justified in detail, but it leads to change in histopathology, immunochemistry of the gastric and duodenal reason of host. The mechanism responsible for bacteria tissue tropism and mucosal damage in stomach variance during the disease is not clearly described and understood scientifically in treatment and control of pathogenic organisms. Polyphenols are secondary metabolites of plants and are generally involved in defense against aggression by pathogens. 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one and 1-hydroxy-5,7-dimethoxy-2-naphthalene-carboxaldehyde are polyphenolic compound obtained from popular Indian medicinal plants ghavpatta (ArgeriaspeciosaLinn.f) andBael (Aeglemarmelos) have long been used in traditional Ayurvedic Indian medicine for various diseases. They have promising effects on ulcer, as detailed investigation has made in our laboratory. Therefore, the aim of present study is to explore membrane –dependent morphogenesis of H. pylori and associated apoptosis-mediated cell death. Based on this we analyzed immune gene expression in stomach of experimental animals with H. pylori, using quantitative reverse transcription polymerase chain reaction(q RT-PCR). This revealed rapid induction of prostaglandin, interferon I (INF-I), interferon II (INF-II) and INF-I associated genes in the infected animal. Ultrastructural changes associated with H. pylori will be taken for advanced studies. This investigation shows that the biomarkers eradicate H. pylori bacterium caused gastric ulcer which is a major risk factor for gastric cancer.

Keywords: gastric ulcer, Helicobacter pylori, immunochemistry, polyphenols

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31 Management of Autoimmune Diseases with Ayurveda

Authors: Simmi Chopra

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In the last few years, there has been a surge of Autoimmune diseases that have become more like an epidemic all over the world. The reasons vary from stress, insufficient sleep, smoking, genetics, environmental pollution, adulterated foods, and a diet full of “the deadly white,” which is white sugar and white flour. Most of the people diagnosed with these diseases are given steroids, opioids, supplements, or elimination diets to manage their lives, but most of them continue suffering to varying degrees. On the other hand, Ayurveda can help manage autoimmune problems effectively. Ayurveda is a 5000 years old holistic medical system from India that has an individualistic approach where health problems are looked at from the lens of balancing body and mind and by targeting the root cause of the problem. A combination of diet and lifestyle according to Ayurvedic principles, Ayurvedic herbal formulations and Ayurvedic therapies can help in the management of autoimmune and other chronic diseases. Panchkarma, which is an intense six weeks detox method, helps balance our body and mind, and has been very effective in managing autoimmune problems. The paper will introduce the basic concepts of Ayurveda and describe the terminologies- doshas, agni and ama. The paper will discuss the importance of diet and lifestyle according to the individual’s imbalance in the three functional parameters - doshas, which govern every aspect of our body and mind, our cells and tissues. The significance of agni, which can be correlated to digestive strength and ama, which can be correlated to toxins that are formed in our body leading to health problems, will be outlined. The Ayurvedic pathophysiology of autoimmune diseases will be discussed with emphasis on Rheumatoid arthritis, Multiple sclerosis and Psoriasis. Ayurvedic management will be discussed for these autoimmune conditions. As Ayurveda is an individualistic system, one protocol will not work for everyone. Therefore, case studies with Ayurvedic protocols for the above autoimmune disease will be presented. Conclusion: Ayurveda can help in managing as well as arresting the progression of autoimmune problems. Ayurveda is an ancient medical system, is much more needed today than ever. It is a tried and tested holistic system which has been practiced for the past many generations in India.

Keywords: ayurveda, autoimmune, diseases, nutrition

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30 Gut Mycobiome Dysbiosis and Its Impact on Intestinal Permeability in Attention-Deficit/Hyperactivity Disorder

Authors: Liang-Jen Wang, Sung-Chou Li, Yuan-Ming Yeh, Sheng-Yu Lee, Ho-Chang Kuo, Chia-Yu Yang

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Background: Dysbiosis in the gut microbial community might be involved in the pathophysiology of attention deficit/hyperactivity disorder (ADHD). The fungal component of the gut microbiome, namely the mycobiota, is a hyperdiverse group of multicellular eukaryotes that can influence host intestinal permeability. This study therefore aimed to investigate the impact of fungal mycobiome dysbiosis and intestinal permeability on ADHD. Methods: Faecal samples were collected from 35 children with ADHD and from 35 healthy controls. Total DNA was extracted from the faecal samples, and the internal transcribed spacer (ITS) regions were sequenced using high-throughput next-generation sequencing (NGS). The fungal taxonomic classification was analysed using bioinformatics tools, and the differentially expressed fungal species between the ADHD and healthy control groups were identified. An in vitro permeability assay (Caco-2 cell layer) was used to evaluate the biological effects of fungal dysbiosis on intestinal epithelial barrier function. Results: The β-diversity (the species diversity between two communities), but not α-diversity (the species diversity within a community), reflected the differences in fungal community composition between ADHD and control groups. At the phylum level, the ADHD group displayed a significantly higher abundance of Ascomycota and significantly lower abundance of Basidiomycota than the healthy control group. At the genus level, the abundance of Candida (especially Candida albicans) was significantly increased in ADHD patients compared to the healthy controls. In addition, the in vitro cell assay revealed that C. albicans secretions significantly enhanced the permeability of Caco-2 cells. Conclusions: The current study is the first to explore altered gut mycobiome dysbiosis using the NGS platform in ADHD. The findings from this study indicated that dysbiosis of the fungal mycobiome and intestinal permeability might be associated with susceptibility to ADHD.

Keywords: ADHD, fungus, gut–brain axis, biomarker, child psychiatry

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29 T Cell Immunity Profile in Pediatric Obesity and Asthma

Authors: Mustafa M. Donma, Erkut Karasu, Burcu Ozdilek, Burhan Turgut, Birol Topcu, Burcin Nalbantoglu, Orkide Donma

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The mechanisms underlying the association between obesity and asthma may be related to a decreased immunological tolerance induced by a defective function of regulatory T cells (Tregs). The aim of this study is to establish the potential link between these diseases and CD4+, CD25+ FoxP3+ Tregs as well as T helper cells (Ths) in children. This is a prospective case control study. Obese (n:40), asthmatic (n:40), asthmatic obese (n:40), and healthy children (n:40), who don't have any acute or chronic diseases, were included in this study. Obese children were evaluated according to WHO criteria. Asthmatic patients were chosen based on GINA criteria. Parents were asked to fill up the questionnaire. Informed consent forms were taken. Blood samples were marked with CD4+, CD25+ and FoxP3+ in order to determine Tregs and Ths by flow cytometric method. Statistical analyses were performed. p≤0.05 was chosen as meaningful threshold. Tregs exhibiting anti-inflammatory nature were significantly lower in obese (0,16%; p≤0,001), asthmatic (0,25%; p≤0,01) and asthmatic obese (0,29%; p≤0,05) groups than the control group (0,38%). Ths were counted higher in asthma group than the control (p≤0,01) and obese (p≤0,001)) groups. T cell immunity plays important roles in obesity and asthma pathogeneses. Decreased numbers of Tregs found in obese, asthmatic and asthmatic obese children may help to elucidate some questions in pathophysiology of these diseases. For HOMA-IR levels, any significant difference was not noted between control and obese groups, but statistically higher values were found for obese asthmatics. The values obtained in all groups were found to be below the critical cut off points. This finding has made the statistically significant difference observed between Tregs of obese, asthmatic, obese asthmatic, and control groups much more valuable. These findings will be useful in diagnosis and treatment of these disorders and future studies are needed. The production and propagation of Tregs may be promising in alternative asthma and obesity treatments.

Keywords: asthma, flow cytometry, pediatric obesity, T cells

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28 Assessment of Platelet and Lymphocyte Interaction in Autoimmune Hyperthyroidism

Authors: Małgorzata Tomczyńska, Joanna Saluk-Bijak

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Background: Graves’ disease is a frequent organ-specific autoimmune thyroid disease, which characterized by the presence of different kind autoantibodies, that, in most cases, act as agonists of the thyrotropin receptor, leading to hyperthyroidism. Role of platelets and lymphocytes can be modulated in the pathophysiology of thyroid autoimmune diseases. Interference in the physiology of platelets can lead to enhanced activity of these cells. Activated platelets can bind to circulating lymphocytes and to affect lymphocyte adhesion. Platelets and lymphocytes can regulate mutual functions. Therefore, the activation of T lymphocytes, as well as blood platelets, is associated with the development of inflammation and oxidative stress within the target tissue. The present study was performed to investigate a platelet-lymphocyte relation by assessing the degree of their mutual aggregation in whole blood of patients with Graves’ disease. Also, the purpose of this study was to examine the impact of platelet interaction on lymphocyte migration capacity. Methods: 30 patients with Graves’ disease were recruited in the study. The matched 30 healthy subjects were served as the control group. Immunophenotyping of lymphocytes was carried out by flow cytometry method. A CytoSelect™ Cell Migration Assay Kit was used to evaluate lymphocyte migration and adhesion to blood platelets. Visual assessment of lymphocyte-platelet aggregate morphology was done using confocal microscope after magnetic cell isolation by Miltenyi Biotec. Results: The migration and functional responses of lymphocytes to blood platelets were greater in the group of Graves’ disease patients compared with healthy controls. The group of Graves’ disease patients exhibited a reduced T lymphocyte and a higher B cell count compared with controls. Based on microscopic analysis, more platelet-lymphocyte aggregates were found in patients than in control. Conclusions: Studies have shown that in Graves' disease, lymphocytes show increased platelet affinity, more strongly migrating toward them, and forming mutual cellular conglomerates. This may be due to the increased activation of blood platelets in this disease.

Keywords: blood platelets, cell migration, Graves’ disease, lymphocytes, lymphocyte-platelet aggregates

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27 Downregulation of Epidermal Growth Factor Receptor in Advanced Stage Laryngeal Squamous Cell Carcinoma

Authors: Sarocha Vivatvakin, Thanaporn Ratchataswan, Thiratest Leesutipornchai, Komkrit Ruangritchankul, Somboon Keelawat, Virachai Kerekhanjanarong, Patnarin Mahattanasakul, Saknan Bongsebandhu-Phubhakdi

Abstract:

In this globalization era, much attention has been drawn to various molecular biomarkers, which may have the potential to predict the progression of cancer. Epidermal growth factor receptor (EGFR) is the classic member of the ErbB family of membrane-associated intrinsic tyrosine kinase receptors. EGFR expression was found in several organs throughout the body as its roles involve in the regulation of cell proliferation, survival, and differentiation in normal physiologic conditions. However, anomalous expression, whether over- or under-expression is believed to be the underlying mechanism of pathologic conditions, including carcinogenesis. Even though numerous discussions regarding the EGFR as a prognostic tool in head and neck cancer have been established, the consensus has not yet been met. The aims of the present study are to assess the correlation between the level of EGFR expression and demographic data as well as clinicopathological features and to evaluate the ability of EGFR as a reliable prognostic marker. Furthermore, another aim of this study is to investigate the probable pathophysiology that explains the finding results. This retrospective study included 30 squamous cell laryngeal carcinoma patients treated at King Chulalongkorn Memorial Hospital from January 1, 2000, to December 31, 2004. EGFR expression level was observed to be significantly downregulated with the progression of the laryngeal cancer stage. (one way ANOVA, p = 0.001) A statistically significant lower EGFR expression in the late stage of the disease compared to the early stage was recorded. (unpaired t-test, p = 0.041) EGFR overexpression also showed the tendency to increase recurrence of cancer (unpaired t-test, p = 0.128). A significant downregulation of EGFR expression was documented in advanced stage laryngeal cancer. The results indicated that EGFR level correlates to prognosis in term of stage progression. Thus, EGFR expression might be used as a prevailing biomarker for laryngeal squamous cell carcinoma prognostic prediction.

Keywords: downregulation, epidermal growth factor receptor, immunohistochemistry, laryngeal squamous cell carcinoma

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26 Anaesthetic Management of Congenitally Corrected Transposition of Great Arteries with Complete Heart Block in a Parturient for Emergency Caesarean Section

Authors: Lokvendra S. Budania, Yogesh K Gaude, Vamsidhar Chamala

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Introduction: Congenitally corrected transposition of great arteries (CCTGA) is a complex congenital heart disease where there are both atrioventricular and ventriculoarterial discordances, usually accompanied by other cardiovascular malformations. Case Report: A 24-year-old primigravida known case of CCTGA at 37 weeks of gestation was referred to our hospital for safe delivery. Her electrocardiogram showed HR-40/pm, echocardiography showed Ejection Fraction of 65% and CCTGA. Temporary pacemaker was inserted by cardiologist in catheterization laboratory, before giving trial of labour in view of complete heart block. She was planned for normal delivery, but emergency Caesarean section was planned due to non-reassuring foetal Cardiotocography Pre-op vitals showed PR-50 bpm with temporary pacemaker, Blood pressure-110/70 mmHg, SpO2-99% on room air. Nil per oral was inadequate. Patency of two peripheral IV cannula checked and left radial arterial line secured. Epidural Anaesthesia was planned, and catheter was placed at L2-L3. Test dose was given, Anaesthesia was provided with 5ml + 5ml of 2% Lignocaine with 25 mcg Fentanyl and further 2.5Ml of 0.5% Bupivacaine was given to achieve a sensory level of T6. Cesarean section was performed and baby was delivered. Cautery was avoided during this procedure. IV Oxytocin (15U) was added to 500 mL of ringer’s lactate. Hypotension was treated with phenylephrine boluses. Patient was shifted to post-operative care unit and later to high dependency unit for monitoring. Post op vitals remained stable. Temporary pacemaker was removed after 24 hours of surgery. Her post-operative period was uneventful and discharged from hospital. Conclusion: Rare congenital cardiac disorders require detail knowledge of pathophysiology and associated comorbidities with the disease. Meticulously planned and carefully titrated neuraxial techniques will be beneficial for such cases.

Keywords: congenitally corrected transposition of great arteries, complete heart block, emergency LSCS, epidural anaesthesia

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25 Coherent Optical Tomography Imaging of Epidermal Hyperplasia in Vivo in a Mouse Model of Oxazolone Induced Atopic Dermatitis

Authors: Eric Lacoste

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Laboratory animals are currently widely used as a model of human pathologies in dermatology such as atopic dermatitis (AD). These models provide a better understanding of the pathophysiology of this complex and multifactorial disease, the discovery of potential new therapeutic targets and the testing of the efficacy of new therapeutics. However, confirmation of the correct development of AD is mainly based on histology from skin biopsies requiring invasive surgery or euthanasia of the animals, plus slicing and staining protocols. However, there are currently accessible imaging technologies such as Optical Coherence Tomography (OCT), which allows non-invasive visualization of the main histological structures of the skin (like stratum corneum, epidermis, and dermis) and assessment of the dynamics of the pathology or efficacy of new treatments. Briefly, female immunocompetent hairless mice (SKH1 strain) were sensitized and challenged topically on back and ears for about 4 weeks. Back skin and ears thickness were measured using calliper at 3 occasions per week in complement to a macroscopic evaluation of atopic dermatitis lesions on back: erythema, scaling and excoriations scoring. In addition, OCT was performed on the back and ears of animals. OCT allows a virtual in-depth section (tomography) of the imaged organ to be made using a laser, a camera and image processing software allowing fast, non-contact and non-denaturing acquisitions of the explored tissues. To perform the imaging sessions, the animals were anesthetized with isoflurane, placed on a support under the OCT for a total examination time of 5 to 10 minutes. The results show a good correlation of the OCT technique with classical HES histology for skin lesions structures such as hyperkeratosis, epidermal hyperplasia, and dermis thickness. This OCT imaging technique can, therefore, be used in live animals at different times for longitudinal evaluation by repeated measurements of lesions in the same animals, in addition to the classical histological evaluation. Furthermore, this original imaging technique speeds up research protocols, reduces the number of animals and refines the use of the laboratory animal.

Keywords: atopic dermatitis, mouse model, oxzolone model, histology, imaging

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24 Evaluation of Neuroprotective Potential of Olea europaea and Malus domestica in Experimentally Induced Stroke Rat Model

Authors: Humaira M. Khan, Kanwal Asif

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Ischemic stroke is a neurological disorder with a complex pathophysiology associated with motor, sensory and cognitive deficits. Major approaches developed to treat acute ischemic stroke fall into two categories, thrombolysis and neuroprotection. The objectives of this study were to evaluate the neuroprotective and anti-thrombolytic effects of Olea europaea (olive oil) and Malus domestica (apple cider vinegar) and their combination in rat stroke model. Furthermore, histopathological analysis was also performed to assess the severity of ischemia among treated and reference groups. Male albino rats (12 months age) weighing 300- 350gm were acclimatized and subjected to middle cerebral artery occlusion method for stroke induction. Olea europaea and Malus domestica was administered orally in dose of 0.75ml/kg and 3ml/kg and combination was administered at dose of 0.375ml/kg and 1.5ml/kg prophylactically for consecutive 21 days. Negative control group was dosed with normal saline whereas piracetam (250mg/kg) was administered as reference. Neuroprotective activity of standard piracetam, Olea europaea, Malus domestica and their combination was evaluated by performing functional outcome tests i.e. Cylinder, pasta, ladder run, pole and water maize tests. Rats were subjected to surgery after 21 days of treatment for analysis from stroke recovery. Olea europaea and Malus domestica in individual doses of 0.75ml/kg and 3ml/kg respectively showed neuroprotection by significant improvement in ladder run test (121.6± 0.92;128.2 ± 0.73) as compare to reference (125.4 ± 0.74). Both test doses showed significant neuroprotection as compare to reference (9.60 ± 0.50) in pasta test (8.40 ± 0.24;9.80 ± 0.37) whereas with cylinder test, experimental groups showed significant increase in movements (6.60 ± 0.24; 8.40 ± 0.24) in contrast to reference (7.80 ± 0.37).There was a decrease in percentage time taken f to reach the hidden maize in water maize test (56.80 ± 0.58;61.80 ± 0.66) at doses 0.75ml/kg and 3ml/kg respectively as compare to piracetam (59.40 ± 1.07). Olea europaea and Malus domestica individually showed significant reduction in duration of mobility (127.0 ± 0.44; 123.0 ± 0.44) in pole test as compare to piracetam (124.0 ± 0.70). Histopathological analysis revealed the significant extent of protection from ischemia after prophylactic treatments. Hence it is concluded that Olea europaea and Malus domestica are effective neuroprotective agents alone as compare to their combination.

Keywords: ischemia, Malus domestica, neuroprotection, Olea europaea

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23 The Maps of Meaning (MoM) Consciousness Theory

Authors: Scott Andersen

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Perhaps simply and rather unadornedly, consciousness is having multiple goals for action and the continuously adjudication of such goals to implement action, referred to as the Maps of Meaning (MoM) Consciousness Theory. The MoM theory triangulates through three parallel corollaries, action (behavior), mechanism (morphology/pathophysiology), and goals (teleology). (1) An organism’s consciousness contains a fluid, nested goals. These goals are not intentionality, but intersectionality, embodiment meeting the world. i.e., Darwinian inclusive fitness or randomization, then survival of the fittest. These goals form via gradual descent under inclusive fitness, the goals being the abstraction of a ‘match’ between the evolutionary environment and organism. Human consciousness implements the brain efficiency hypothesis, genetics, epigenetics, and experience crystallize efficiencies, not necessitating best or objective but fitness, i.e., perceived efficiency based on one’s adaptive environment. These efficiencies are objectively arbitrary, but determine the operation and level of one’s consciousness, termed extreme thrownness. Since inclusive fitness drives efficiencies in physiologic mechanism, morphology and behavior (action) and originates one’s goals, embodiment is necessarily entangled to human consciousness as its the intersection of mechanism or action (both necessitating embodiment) occurring in the world that determines fitness. Perception is the operant process of consciousness and is the consciousness’ de facto goal adjudication process. Goal operationalization is fundamentally efficiency-based via one’s unique neuronal mapping as a byproduct of genetics, epigenetics, and experience. Perception involves information intake and information discrimination, equally underpinned by efficiencies of inclusive fitness via extreme thrownness. Perception isn’t a ‘frame rate,’ but Bayesian priors of efficiency based on one’s extreme thrownness. Consciousness and human consciousness is a modular (i.e., a scalar level of richness, which builds up like building blocks) and dimensionalized (i.e., cognitive abilities become possibilities as emergent phenomena at various modularities, like stratified factors in factor analysis). The meta dimensions of human consciousness seemingly include intelligence quotient, personality (five-factor model), richness of perception intake, and richness of perception discrimination, among other potentialities. Future consciousness research should utilize factor analysis to parse modularities and dimensions of human consciousness and animal models.

Keywords: consciousness, perception, prospection, embodiment

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22 Intracranial Hypotension: A Brief Review of the Pathophysiology and Diagnostic Algorithm

Authors: Ana Bermudez de Castro Muela, Xiomara Santos Salas, Silvia Cayon Somacarrera

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The aim of this review is to explain what is the intracranial hypotension and its main causes, and also to approach to the diagnostic management in the different clinical situations, understanding radiological findings, and physiopathological substrate. An approach to the diagnostic management is presented: what are the guidelines to follow, the different tests available, and the typical findings. We review the myelo-CT and myelo-RM studies in patients with suspected CSF fistula or hypotension of unknown cause during the last 10 years in three centers. Signs of intracranial hypotension (subdural hygromas/hematomas, pachymeningeal enhancement, venous sinus engorgement, pituitary hyperemia, and lowering of the brain) that are evident in baseline CT and MRI are also sought. The intracranial hypotension is defined as a lower opening pressure of 6 cmH₂O. It is a relatively rare disorder with an annual incidence of 5 per 100.000, with a female to male ratio 2:1. The clinical features it’s an orthostatic headache, which is defined as development or aggravation of headache when patients move from a supine to an upright position and disappear or typically relieve after lay down. The etiology is a decrease in the amount of cerebrospinal fluid (CSF), usually by loss of it, either spontaneous or secondary (post-traumatic, post-surgical, systemic disease, post-lumbar puncture etc.) and rhinorrhea and/or otorrhea may exist. The pathophysiological mechanisms of hypotension and CSF hypertension are interrelated, as a situation of hypertension may lead to hypotension secondary to spontaneous CSF leakage. The diagnostic management of intracranial hypotension in our center includes, in the case of being spontaneous and without rhinorrhea and/or otorrhea and according to necessity, a range of available tests, which will be performed from less to more complex: cerebral CT, cerebral MRI and spine without contrast and CT/MRI with intrathecal contrast. If we are in a situation of intracranial hypotension with the presence of rhinorrhea/otorrhea, a sample can be obtained for the detection of b2-transferrin, which is found in the CSF physiologically, as well as sinus CT and cerebral MRI including constructive interference steady state (CISS) sequences. If necessary, cisternography studies are performed to locate the exact point of leakage. It is important to emphasize the significance of myelo-CT / MRI to establish the diagnosis and location of CSF leak, which is indispensable for therapeutic planning (whether surgical or not) in patients with more than one lesion or doubts in the baseline tests.

Keywords: cerebrospinal fluid, neuroradiology brain, magnetic resonance imaging, fistula

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