Search results for: mitochondrial dysfunction

Authors: Nana Gorgiladze, Tamar Gaprindashvili, Mikheil Shavdia, Zurab Pagava

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Introduction/Purpose Chemotherapy is a common treatment for breast cancer, but it can also cause damage to the heart and blood vessels. This damage, known as cancer therapy-related cardiovascular toxicity (CTR-CVT), can increase the risk of heart failure and death in breast cancer patients. The left ventricle is often affected by CTR-CVT, but the right ventricle (RV) may also be vulnerable to CTR-CVT and may show signs of dysfunction before the left ventricle. The study aims to investigate how the RV function changes during chemotherapy for breast cancer by using conventional echocardiographic and global longitudinal strain (GLS) techniques. By measuring the GLS strain of the RV, researchers tend to detect early signs of CTR-CVT and improve the management of breast cancer patients. Methods The study was conducted on 28 women with low cardiovascular risk who received anthracycline chemotherapy for breast cancer. Conventional 2D echocardiography (LVEF, RVS’, TAPSE) and speckle-tracking echocardiography (STE) measurements of the left and right ventricles (LVGLS, RVGLS) were used to assess cardiac function before and after chemotherapy. All patients had normal LVEF at the beginning of the study. Cardiotoxicity was defined as a new LVEF reduction of 10 percentage points to an LVEF of 40-49% and/or a new decline in GLS of 15% from baseline, as proposed by the most recent cardio-oncology guideline. ResultsThe research found that the LVGLS decreased from -21.2%2.1% to -18.6%2.6% (t-test = -4.116; df = 54, p=0.001). The change in value LV-GLS was 2.6%3.0%. The mean percentage change of the LVGLS was 11,6%13,3%; p=0.001. Similarly, the right ventricular global longitudinal strain (RVGLS) decreased from -25.2%2.9% to -21.4%4.4% (t-test = -3.82; df = 54, p=0.001). The RV-GLS value of change was 3.8%3.6%. Likewise, the percentage decrease of the RVGLS was 15,0%14,3%, p=0.001.However, the measurements of the right ventricular systolic function (RVS) and tricuspid annular plane systolic excursion (TAPSE) were insignificant, and the left ventricular ejection fraction ( LVEF) remained unchanged.

Keywords: cardiotoxicity, chemotherapy, GLS, right ventricle

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Authors: Vahab Behmanesh

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Metabolic syndrome is defined as having at least three of the five metabolic risk factors, including abdominal obesity, high blood pressure, high triglycerides, low HDL, and insulin resistance. Lifestyle changes towards reducing physical activity, unhealthy eating habits Especially the high-fat and high-carbohydrate diet is directly related to metabolic syndrome, and due to the epidemic of overweight and sedentary life, metabolic syndrome is a serious problem worldwide. On the other hand, vitamin D deficiency is considered as one of the most common problems in the world, which is related to the dysfunction of beta cells and insulin resistance, and therefore, vitamin D deficiency is considered as a factor in the occurrence of metabolic syndrome. 40 subjects (age: 16.12 ± 4.4 years and body mass index 25.61 ± 4.4 kg/m2) were randomly assigned to groups of aerobic exercise and placebo, aerobic exercise and vitamin D and placebo (no exercise) were divided. Vitamin D was taken at a dose of 50,000 units per week in a double-blind format for eight weeks, and the daily aerobic exercise program was performed for 50 to 60 minutes, three doses per week, with an intensity of 50-60% of the maximum heart rate. From one-way analysis of variance, Factorial variance analysis (2x2) repeated measurement and correlated t-test were used for data analysis. Aerobic exercise and vitamin D intake reduced all metabolic risk indicators and blood insulin (P < 0.05). However, the subjective feeling of hunger did not change significantly (P < 0.05). Regarding waist circumference and blood glucose, the effect of exercise combined with vitamin D consumption was greater than the corresponding effect in the vitamin D group (P < 0.05). Aerobic exercises and vitamin D intake are safe and effective for improving cardiometabolic health, Imam adds vitamin D to the exercise program has more benefits for weight and blood sugar control, which suggests prescribing it for patients with metabolic syndrome.

Keywords: vitamin D, aerobic exercise, metabolic control, adolescents

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Authors: Samantha A. Cintron, Janet Pierce, Mihaela E. Sardiu, Diane Mahoney, Jill Peltzer, Bhanu Gupta, Qiuhua Shen

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High output heart failure (HOHF) is characterized a high output state resulting from an underlying disease process and is commonly caused by obesity. As obesity levels increase, more individuals will be at risk for obesity-related HOHF. However, the underlying pathophysiologic mechanisms of obesity-related HOHF are not well understood and need further research. The aim of the study was to describe the differences in leukocyte transcriptomes of morbidly obese patients with HOHF and those with non-HOHF. In this cross-sectional study, the study team collected blood samples, demographics, and clinical data of six patients with morbid obesity and HOHF and six patients with morbid obesity and non-HOHF. The study team isolated the peripheral blood leukocyte RNA and applied stranded total RNA sequencing. Differential gene expression was calculated, and Ingenuity Pathway Analysis software was used to interpret the canonical pathways, functional changes, upstream regulators, and mechanistic and causal networks that were associated with the significantly different leukocyte transcriptomes. The study team identified 116 differentially expressed genes; 114 were upregulated, and 2 were downregulated in the HOHF group (Benjamini-Hochberg adjusted p-value ≤ 0.05 and log2(fold-change) of ±1). The differentially expressed genes were involved with cell proliferation, mitochondrial function, erythropoiesis, erythrocyte stability, and apoptosis. The top upregulated canonical pathways associated with differentially expressed genes were autophagy, adenosine monophosphate-activated protein kinase signaling, and senescence pathways. Upstream regulator GATA Binding Protein 1 (GATA1) and a network associated with nuclear factor kappa-light chain-enhancer of activated B cells (NF-kB) were also identified based on the different leukocyte transcriptomes of morbidly obese patients with HOHF and non-HOHF. To the author’s best knowledge, this is the first study that reported the differential gene expression in patients with obesity-related HOHF and demonstrated the unique pathophysiologic mechanisms underlying the disease. Further research is needed to determine the role of cellular function and maintenance, inflammation, and iron homeostasis in obesity-related HOHF.

Keywords: cardiac output, heart failure, obesity, transcriptomics

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Authors: Ali Kassem, Aly Taha, Abeer Hassan, Kazuhide Higuchi

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Introduction: Trans arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) is usually followed by hepatic dysfunction that limits its efficacy. L-carnitine is recently studied as hepatoprotective agent. Our aim is to evaluate the L-carnitine effects against the deterioration of liver functions after TACE. Method: 53 patients with intermediate stage HCC were assigned into two groups; L-carnitine group (26 patients) who received L-carnitine 300 mg tablet twice daily from 2 weeks before to 12 weeks after TACE and control group (27 patients) without L-carnitine therapy. 28 of studied patients received branched chain amino acids granules. Results: There were significant differences between L-carnitine Vs. control group in mean serum albumin change from baseline to 1 week and 4 weeks after TACE (p < 0.05). L-Carnitine maintained Child-Pugh score at 1 week after TACE and exhibited improvement at 4 weeks after TACE (p < 0.01 Vs 1 week after TACE). Control group has significant Child-Pugh score deterioration from baseline to 1 week after TACE (p < 0.05) and 12 weeks after TACE (p < 0.05). There were significant differences between L-carnitine and control groups in mean Child-Pugh score change from baseline to 4 weeks (p < 0.05) and 12 weeks after TACE (p < 0.05). L-carnitine displayed improvement in (PT) from baseline to 1 week, 4 w (p < 0.05) and 12 weeks after TACE. PT in control group declined less than baseline along all follow up intervals. Total bilirubin in L-carnitine group decreased at 1 week post TACE while in control group, it significantly increased at 1 week (p = 0.01). ALT and C-reactive protein elevation were suppressed at 1 week after TACE in Lcarnitine group. The hepatoprotective effects of L-carnitine were enhanced by concomitant use of branched chain amino acids. Conclusion: L-carnitine and BCAA combination therapy offer a novel supportive strategy after TACE in HCC patients.

Keywords: hepatocellular carcinoma, L-carnitine, liver functions , trans-arterial embolization

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Authors: E. Von Cheong, Carol Sinnott, Darren Dahly, Patricia M. Kearney

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Introduction and Aim: Adverse childhood experiences (ACEs) are all too common and have been linked to poorer health and wellbeing across the life course. While the prevention of ACEs is a worthy goal, it is important that we also try to lessen the impact of ACEs for those who do experience them. This study aims to investigate associations between adverse childhood experiences (ACEs) and later-life depressive symptoms; and to explore whether perceived social support (PSS) moderates these. Method: We analysed baseline data from the Mitchelstown (Ireland) 2010-11 cohort involving 2047 men and women aged 50–69 years. Self-reported assessments included ACEs (Centre for Disease Control ACE questionnaire), PSS (Oslo Social Support Scale), and depressive symptoms (CES-D). The primary exposure was self-report of at least one ACE. We also investigated the effects of ACE exposure by the subtypes abuse, neglect, and household dysfunction. Associations between each of these exposures and depressive symptoms were estimated using logistic regression, adjusted for socio-demographic factors that were selected using the Directed Acyclic Graph (DAG) approach. We also tested whether the estimated associations varied across levels of PSS (poor, moderate, and good). Results: 23.7% of participants reported at least one ACE (95% CI: 21.9% to 25.6%). ACE exposures (overall or subtype) were associated with a higher odds of depressive symptoms, but only among individuals with poor PSS. For example, exposure to any ACE (vs. none) was associated with 3 times the odds of depressive symptoms (Adjusted OR 2.97; 95% CI 1.63 to 5.40) among individuals reporting poor PSS, while among those reporting moderate PSS, the adjusted OR was 1.18 (95% CI 0.72 to 1.94). Discussion: ACEs are common among older adults in Ireland and are associated with higher odds of later-life depressive symptoms among those also reporting poor PSS. Interventions that enhance perception of social support following ACE exposure may help reduce the burden of depression in older populations.

Keywords: adverse childhood experiences, depression, later-life, perceived social support

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Authors: Gopal Lamichhane, Biswash Sapkota, Grinsun Sharma, Mahendra Adhikari

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Urolithiasis is a condition in which insoluble or less soluble salts like oxalate, phosphate etc. precipitate in urinary tract and causes obstruction in ureter resulting renal colic or sometimes haematuria. It is the third most common disorder of urinary tract affecting nearly 2% of world’s population. Poor urinary drainage, microbial infection, oxalate and calcium containing diet, calciferol, hyperparathyroidism, cysteine in urine, gout, dysfunction of intestine, drought environment, lifestyle, exercise, stress etc. are risk factors for urolithiasis. Wide ranges of treatments are available in allopathic system of medicine but reoccurrence is unpreventable even with the surgical removal of stone or lithotripsy. So, people prefer alternative medicinal systems such as Unani, homeopathic, ayurvedic etc. systems of medicine due to their fewer side effects over allopathic counterpart. Different plants based ethnomedicines are being well established by their continuous effective use in human since long time in treatment of urinary problem. Many studies have scientifically proved those ethnomedicines for antiurolithiatic effect in animal and in vitro model. Plant-based remedies were found to be therapeutically effective for both prevention as well as cure of calcium oxalate urolithiasis. Plants were known to show these effects through a combination of many effects such as antioxidant, diuretic, hypocalciuric, urine alkalinizing effect in them. Berberine, triterpenoids, lupeol are the phytochemicals established for antiurolithiatic effect. Hence, plant-based medicine can be the effective herbal alternative as well as means of discovery of novel drug molecule for curing urolithiatic disorder and should be focused on further research to discover their value in coming future.

Keywords: urolithiasis, herbal medicine, ethnomedicine, kidney stone, calcium oxalate

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Authors: Hanen Bouaziz, Moez Rafrafi, Ghada Ben Salah, Kamel Jamoussi, Tahia Boudawara, Najiba Zeghal

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The present study investigated the protective role of Hyparrhenia hirta against sodium nitrate (NaNO3)-induced nephrotoxicity. A high-performance liquid chromatography coupled with a mass spectrometer (HPLC-MS) method was developed to separate and identify flavonoids in Hyparrhenia hirta. Seven flavonoids were identified as 3-O-methylquercetin, luteolin-7-O-glucoside, luteolin, apigenin-7-O-glucoside, apigenin-8-C-glucoside, luteolin-8-C-glucoside and luteolin-6-C-glucoside. Wistar rats were randomly divided into three groups: a control group and two treated groups during 50 days with NaNO3 administered either alone in drinking water or co-administered with Hyparrhenia hirta. NaNO3 treatment induced a significant increase in plasma levels of creatinine, urea and uric while urinary level decreased significantly. Nephrotoxicity induced by NaNO3 was characterized by significant increase in creatinine clearance. In parallel, a significant increase in malondialdehyde level along with a concomitant decrease in total glutathione content and superoxide dismutase, catalase and glutathione peroxidase activities were observed in the kidney after NaNO3 treatment. The histopathological changes in kidney after NaNO3 administration were shrunken. There were renal tubule cell degeneration and infiltration of mononuclear cells. Most glomeruli revealed shrinkage, a wide capsular space and a peri-glomerular mononuclear cells infiltration. Hyparrhenia hirta supplementation showed a remarkable amelioration of the abnormalities cited above. The results concluded that the treatment with Hyparrhenia hirta had a significant role in protecting the animals from nitrate-induced kidney dysfunction.

Keywords: flavonoids, hyparrhenia hirta, kidney, nitrate toxicity, oxidative stress, rat

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Authors: Rashmi Tyagi, Savita Vermani

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Violence against women is the result of long-standing power imbalance between men and women and thus seriously compromises the well-being, productivity and contribution of one half the population. The costs incurred to the family especially children and society at large in terms of physical, psychological, social and financial losses are huge. The communities’ native to the state of Haryana in India is primarily patriarchal, burdened with age old regressive mindset under the socio-cultural and religious structures which discriminates against women. Therefore it was important to bring to light the issues affecting women in this region. Therefore this study focused on studying the consequences of crime on victim women and their families. Two hundred women were randomly selected and out of those one hundred twenty, who were affected with some kind of violence were interviewed. Data was collected and statistically analyzed for physical, psychological, inter-family and societal consequences of violence on these women. Women reported physical injuries, gynecological problems, unwanted pregnancies, frigidity, phobia and sexual dysfunction. 58.9% women felt decreased work efficiency. Psychological problems encountered were anxiety, isolation, depression, suicidal tendencies. 66.7% respondents suffered from anxiety followed by 65.0% faced depression symptoms. At family levels, 40.0% respondents felt the atmosphere was unsuitable for children while 39.2% reported lack of interaction. The societal consequences reported were breakdown of interaction with friends and family (44.2%) and resulting humiliation and demeaning remarks from others (38.3%). The impact of violence on women had an adverse effect on children. 36.7% children felt responsible for abuse and powerless to stop it, 29.2% reported living with fear. Concerted efforts are required to curb violence against women in Haryana.

Keywords: impact of violence against women on children, patriarchal society, physical psychological and societal consequences, violence against women

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Authors: Ayeshmanthe Rathnayake, Siew Goh, Carmel Fenton, Ashutosh Hardikar

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Post-Operative Atrial Fibrillation (POAF) is the most frequent complication of cardiac surgery and is associated with reduced survival, increased rates of cognitive changes and cerebrovascular accident, heart failure, renal dysfunction, infection and length of stay, and hospital costs. Cardiac tamponade, although less common, carries high morbidity and mortality. Shed mediastinal blood in the pericardial space is a major source of intrapericardial oxidative stress and inflammation that triggers POAF. The utilisation of a left posterior pericardiotomy aims to shunt blood from the pericardium into the pleural space and have a role in the prevention of POAF as well as cardiac tamponade. 2118 patients had undergone isolated Coronary Artery Bypass Graft (CABG) at Royal Hobart Hospital from 2008-2021. They were divided into pericardiotomy vs control group. Patient baseline demographics, intraoperative data, and post-operative outcomes were reviewed retrospectively. Total incidence of new POAF and cardiac tamponade was 26.1% and 0.75%, respectively. Primary outcome of both the incidence of POAF(22.9% vs27.8%OR 0.77 p<0.05) and Cardiac Tamponade (0% vs 1.1% OR 0.85 p<0.05) were less in the pericardiotomy group.Increasing age, BMI, poor left ventricular function (EF <30%), and return to theatre were independent predictors of developing POAF. There were similar rates of return to theatre for bleeding however, no cases of tamponade in the pericardiotomy group. There were no complications attributable to left posterior pericardiotomy and the time added to the duration of surgery was minimal. Left posterior pericardiotomy is associated with a significant reduction in the incidence of POAFand cardiac tamponade and issafe and efficient.

Keywords: cardiac surgery, pericardiotomy, post-operative atrial fibrillation, cardiac tamponade

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Authors: Ipek Sensu

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Comorbid Axis I disorders are highly common for suicidal borderline personality disorder (BPD) patients, especially substance use disorder and anxiety disorders. Since interpersonal dysfunction is one of the core symptoms in BPD, the purpose of the current study is to examine perceived criticism and anxiety disorders and also substance abuse disorders (SUD) for women with borderline personality disorder (BPD) who attempt suicide at least once in their lifetime. In the current study, it was suggested that the perceived criticism from others and being upset by criticism differ between suicidal women with BPD with comorbidity of anxiety disorders and SUD (separately) and suicidal women with BPD without anxiety disorders and without SUD (separately). The participants in this study included ninety-nine women who have already been diagnosed with borderline personality disorder and also have had at least two episodes of deliberate self-harm, in other words, suicide attempts and/or non-suicidal self-injury (NSSI) in the last five years and at least one episode in the 8-week period before joining the research study and at least one suicide attempt in the previous year. Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) and Social History Interview (SHI) were conducted to determine the comorbid axis I disorders and level of perceived criticism. As a result of the independent sample t-tests, the first hypothesis was rejected, in other words, women with BPD and a comorbid anxiety disorder did not show significantly higher levels of ‘criticized by others’, compared to women with BPD alone. However, the levels of ‘upset at criticism’ were significantly different between suicidal women with BPD with or without any anxiety disorders, which is the second hypothesis. In addition, the third hypothesis was also accepted; this means, women with BPD who had any substance use dependence would show significantly higher levels of 'criticized by others' compared to women with BPD alone. Finally, the fourth hypothesis was partly accepted: that is, women with BPD with alcohol dependence had significantly higher levels of ‘how upset when they expose to criticism’, compared to those without alcohol dependence. Limitations, implications, and directions for future research are discussed.

Keywords: anxiety disorders, borderline personality disorders, perceived criticism, substance use disorders

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Authors: Soheila Rabiepoor, Elham Sadeghi

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Introduction: Divorce is both a personal and a social issue. Nowadays, due to various factors such as rapid social, economical, and cultural changes, the family structure has undergone many rough changes, out of 3 marriages 2 of them lead to divorce. One of the factors affecting the incidence of divorce and relationship problems between couples is the sexual and marital behaviors. There are several different reasons to suspect that pornography might affect divorce in either a positive or a negative way. Therefore this study evaluated the sexual health of divorce-asking in Urmia, Iran. Methods: This was a cross-sectional descriptive study and was conducted on 71 married women of Urmia, Iran in 2016. Participants were applicants of divorce (referred to divorce center) who were selected by using convenient sampling method. Data gathering tool included the scales for measuring demographic, sexual health (sexual satisfaction and function), and researcher made pornography questions. Data were analyzed based on the SPSS 16 software. P-values less than 0.05 were considered significant. Results: Investigation of demographic features showed that age average of studied samples was 28.98 ± 7.44, with a marriage duration average 8.12 ± 6.53 years (min 1 year/ max 28 years). Most of their education was at diploma (45.1%). 69 % of the women declared their income and expenditure as equal. Nearly 42% of women and 59% of their partner had watched sexual pornography clips. 45.5% of participants reported that they compared own sexual relationship with sexual pornography clips. In the other hand, sexual satisfaction total score was 51.50 ± 17.92. The mean total sexual function score was 16.62 ± 10.58. According to these findings, most of women were experienced sexual dissatisfaction and dysfunction. Conclusions: The results of the study indicated that who had low sexual satisfaction score, had higher rate of watching pornography clips. Based on current study, paying attention to family education and counseling programs especially in the sexual field will be more fruitful.

Keywords: divorce-asking, pornography, sexual satisfaction, sexual function, women

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Authors: Christine Ysabelle G. Roman, Pauline Torres

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Background: Hypertrophic cardiomyopathy is a disease of marked heterogeneity. It is a genetically determined heart disease characterized by significant myocardium hypertrophy that results in diastolic dysfunction, left ventricular outflow tract obstruction, and an increased risk of arrhythmias. The primary treatment in patients with such conditions is negative inotropic drugs, such as beta-blockers, calcium channel antagonists, and disopyramide. However, for those who remain symptomatic and need septal reduction therapy, surgical septal myectomy or alcohol septal ablation are options. Case Summary: A 19 – year old female presented in the authors’ institution with easy fatigability. The consult was done a year prior, and 2D echocardiography was requested which showed concentric left ventricular hypertrophy, asymmetrically hypertrophied interventricular septum (IVS) with the largest diameter of 3.3cm & subaortic dynamic obstruction with a maximum gradient of 47 mmHg. A repeat echo a year later showed asymmetric septal hypertrophy (IVS measuring at 3cm) with the systolic anterior motion of anterior mitral valve leaflet and left ventricular outflow tract obstruction (peak gradient of 50mmHg). The patient then underwent alcohol septal ablation and was discharged stable after four days of admission. Conclusion: Hypertrophic obstructive cardiomyopathy, a cardiovascular genetic disease, results in various patterns of left ventricular hypertrophy and abnormality of mitral valve apparatus. The patient is managed medically initially. However, despite optimal drug therapy and significant left ventricular outflow tract obstruction, significant heart failure symptoms or syncope require invasive treatment.

Keywords: hypertrophic obstructive cardiomyopathy, left ventricular outflow tract obstruction, alcohol septal ablation, alcohol

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Authors: Naouel Boussoualim, Hayat Trabsa, Imane Krache, Seddik Khennouf, Noureddine Charef, Lekhmici Arrar, Abderrahmane Baghiani

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Purpose: To evaluate the in-vitro inhibition of xanthine oxidase (purified from bovine milk) by extracts of Lycium arabicum, as well as it is in vivo hypouricemic and renal protective effects. Methods: Four extracts of Lycium arabicum, methanol (CrE), chloroform (ChE), ethyl acetate (EaE) and aqueous (AqE) extracts, were screened for their total phenolics and potential inhibitory effects on purified bovine milk xanthine oxidase (XO) activity by measuring the formation of uric acid or superoxide radical. The mode of inhibition was investigated and compared with the standard drugs, allopurinol, quercitin, and catechin. To evaluate their hypouricemic effect, the extracts were administered to potassium oxonate-induced hyperuricemic mice at a dose of 50 mg/kg body weight. Results: The results showed that EaE had the highest content of phenolic compounds and was the most potent inhibitor of uric acid formation (IC50 = 0.017 ± 0.001 mg/mL) and formation of superoxide (IC50 = 0.035 ± 0.001 mg/ml). Lineweaver-Burk analysis showed that CrE and EaE inhibited XO competitively, whereas the inhibitory activities exerted by ChE and AqE were of a mixed type. Intraperetoneal injection of L. arabicum extracts (50 mg/kg) elicited hypouricemic actions in hyperuricemic mice. Hyperuricemic mice presented a serum uric acid concentration of 4.71 ± 0.29 mg/L but this was reduced to 1.78 ± 0.11 mg/L by EaE, which was the most potent hyporuricemic extract. Conclusion: L. arabicum fractions have a strong inhibitory effect on xanthine oxidase and and also have a significantly lowering effect on serum and liver creatinine and urea levels in hyperuricemic mice.

Keywords: lycium arabicum, uric acid, creatinine, superoxide, phenolic compounds, flavonoids, hyperuricemia

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Authors: Abir Dey, Shams Noman

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Introduction: Offshore Island is the remote and isolated area from the terrestrial mainland. They are deprived of their needs. The children from an offshore island are usually underserved in the case of health care because it is a remote area where the health care systems are quite poor compared to mainland. So, the proper information is required for appropriate planning to reduce underlying causes behind visual deprivation among the surviving children of the Offshore Island. Purpose: The purpose of this study was to determine ocular morbidities, knowledge, and barriers of eye care services among children in an Offshore Island. Methods: The study team visited, and all data were collected from different rural communities at Sandwip Upazila, Chittagong district for screening the children aged 5-16 years old by doing spot examination. The whole study was conducted in both qualitative and quantitative methods. To determine ocular status of children, examinations were done under skilled Ophthalmologists and Optometrists. A focus group discussion was held. The sample size was 490. It was a community based descriptive study and the sampling method was purposive sampling. Results: In total 490 children, about 56.90% were female and 43.10% were male. Among them 456 were school-going children (93.1%) and 34 were non-school going children (6.9%). In this study the most common ocular morbidity was Allergic Conjunctivitis (35.2%). Other mentionable ocular morbidities were Refractive error (27.7%), Blepharitis (13.8%), Meibomian Gland Dysfunction (7.5%), Strabismus (6.3%) and Amblyopia (6.3%). Most of the non-school going children were involved in different types of domestic work like farming, fishing, etc. About 90.04% children who had different ocular abnormalities could not attend to the doctor due to various reasons. Conclusions: The ocular morbidity was high in rate on the offshore island. Eye health care facility was also not well established there. Awareness should be raised about necessity of maintaining hygiene and eye healthcare among the island people. Timely intervention through available eye care facilities and management can reduce the ocular morbidity rate in that area.

Keywords: morbidities, screening, barriers, offshore island, knowledge

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Authors: I. Boroňová, J. Bernasovská, J. Kmec, E. Petrejčíková

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Dilated cardiomyopathy (DCM) is a primary myocardial disease, it is characterized by progressive systolic dysfunction due to cardiac chamber dilatation and inefficient myocardial contractility with estimated prevalence of 37 in 100 000 people. It is the most frequent cause of heart failure and cardiac transplantation in young adults. About one-third of all patients have a suspected familial disease indicating a genetic basis of DCM. Many candidate gene studies in humans have tested the association of single nucleotide polymorphisms (SNPs) in various genes coding for proteins with a known cardiovascular function. In our study we present the results of ZBTB17 gene rs10927875 polymorphism genotyping in relation to dilated cardiomyopathy in Slovak population. The study included 78 individuals, 39 patients with DCM and 39 healthy control persons. The mean age of patients with DCM was 50.7±11.5 years; the mean age of individuals in control group was 51.3±9.8 years. Risk factors detected at baseline in each group included age, sex, body mass index, smoking status, diabetes and blood pressure. Genomic DNA was extracted from leukocytes by a standard methodology and screened for rs10927875 polymorphism in intron of ZBTB17 gene using Real-time PCR method (Step One Applied Biosystems). The distribution of investigated genotypes for rs10927875 polymorphism in the group of patients with DCM was as follows: CC (89.74%), CT (10.26%), TT (0%), and the distribution in the control group: CC (92.31%), CT (5.13%), and TT (2.56%). Using the chi-square (χ2) test we compared genotype and allele frequencies between patients and controls. There was no difference in genotype or allele frequencies in ZBTB17 gene rs10927875 polymorphism between patients and control group (χ2=3.028, p=0.220; χ2=0.264, p=0.608). Our results represent an initial study, it can be considered as preliminary and first of its kind in Slovak population. Further studies of ZBTB17 gene polymorphisms of more numerous files and additional functional investigations are needed to fully understand the role of genetic associations.

Keywords: dilated cardiomyopathy, SNP polymorphism, ZBTB17 gene, bioscience

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Authors: Jemini Vyas, Oluwatobi Adeyoe, Jenny Branagan, Chandran Tanabalan, John Beatty, Aakash Pai

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Introduction: The development of robotic surgery has accelerated centralisation to tertiary centres, where robotic radical prostatectomy (RP) is offered. The purpose of concentrating treatment in high volume specialist centres is to improve the quality of care and patient outcomes. The aim of this study was to assess the impact on clinical outcomes of centralisation for locally diagnosed patients undergoing RP. Methods: Clinical outcomes for 169 consecutive laparoscopic & open RP pre-centralisation were retrospectively compared with 50 consecutive robotic RP conducted over a similar period post-centralisation. Preoperative risk stratification and time to surgery were collected. Perioperative outcomes, including length of stay (LOS) and complications, were collated. Post-operative outcomes, including erectile dysfunction (ED), biochemical recurrence (BCR), and urinary continence, were assessed. Results: Preoperative risk stratification showed no difference between the two groups. The median time from diagnosis to treatment was similar between the two groups (pre-centralisation, 121 days, post-centralisation, 117 days). The mean length of stay (pre-centralisation, 2.1 days, post-centralisation, 1.6 days) showed no significant difference (p=0.073). Proportion of overall complications (pre-centralisation, 11.4%, post-centralisation, 8.7%) and complications, above Clavien-Dindo 2, were similar between the two groups (pre-centralisation1.2%, post-centralisation 2.2%). Post operative functional parameters, including continence and ED, were comparable. Five-year BCR free rate was 78% for the pre-centralisation group and 79% for the post centralisation group. Conclusion: For our cohort of patients, clinical outcomes have remained static during centralisation. It is imperative that centralisation is accompanied by increased capacity, streamlining of pathways, and training to ensure that improved quality of care is achieved. Our institution has newly acquired a robot, and prospectively studying this data may support the reversal of centralisation for RP surgery.

Keywords: prostate, cancer, prostatectomy, clinical

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Authors: Courtney Manthey-Pierce, Anna Warrener

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Polycystic ovarian syndrome (PCOS) is the most common endocrine disruptive disorder in females. PCOS is primarily characterized by polycystic ovaries, anovulation, hirsutism, insulin resistance, and hyperandrogenism. Despite negative reproductive consequences for females from anovulation and endocrine dysfunction, genes associated with the pathogenesis of PCOS are highly hereditable (h2 = 0.72). An evolutionary mismatch occurs when a trait that evolved in one environment has become maladaptive in another environment. The idea that PCOS is an evolutionary mismatch disease has been promoted by several researchers. Each trait of the resulting PCOS phenotype should be investigated individually in order to demonstrate an evolutionary mismatch. Hyperandrogenism is often regarded as the main characteristic of PCOS Hyperandrogenism may have aided with conception in older females, increased bone mineral density, and supported prolonged breastfeeding in nutritionally distressed populations. Because of the high prevalence of PCOS in the modern world, approximately 6%, it is often argued that PCOS emerged in an ancestral population prior to the migration out of Africa approximately 200,000 years ago. This environment would be characterized by sporadic periods of nutrition deficit and resource hardships as the climate began changing. Presently, modern society is characterized by obesity and sedentary lifestyles. The prevalence of obesity renders hyperandrogenism PCOS useless as there are no periods of nutritional distress requiring androgens for increased reproductive rates. In an ancestral environment, hyperandrogenism would likely lead to sporadic anovulation and mild secondary symptoms, however high levels of androgens in a modern environment led to prolonged if not permanent infertility and excessive secondary problems. Thus, hyperandrogenism related to PCOS appears to meet evolutionary mismatch criteria. Seen in this light, PCOS may be effectively treated as a probably evolutionary mismatch.

Keywords: evolutionary mismatch, heritability, hyperandrogenism, mismatch disorder

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Authors: Ravinder Kaur

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Introduction Global cerebrovascular reactivity (CVR) mapping is a promising clinical assessment for stress-testing the brain using physiological challenges, such as CO₂, to elicit changes in perfusion. It enables real-time assessment of cerebrovascular integrity and health. Conventional imaging approaches solely use steady-state parameters, like cerebral blood flow (CBF), to evaluate the integrity of the resting parenchyma and can erroneously show a healthy brain at rest, despite the underlying pathogenesis in the presence of cerebrovascular disease. Conversely, coupling CO₂ inhalation with phase-contrast MRI neuroimaging interrogates the capacity of the vasculature to respond to changes under stress. It shows promise in providing prognostic value as a novel health marker to measure neurovascular function in disease and to detect early brain vasculature dysfunction. Objective This exploratory study was established to:(a) quantify the CBF response to CO₂ in hypocapnia and hypercapnia,(b) evaluate disparities in CVR between internal carotid (ICA) and vertebral artery (VA), and (c) assess sex-specific variation in CVR. Methodology Phase-contrast MRI was employed to measure the cerebrovascular reactivity to CO₂ (±10 mmHg). The respiratory interventions were presented using the prospectively end-tidal targeting RespirActTM Gen3 system. Post-processing and statistical analysis were conducted. Results In 9 young, healthy subjects, the CBF increased from hypocapnia to hypercapnia in all vessels (4.21±0.76 to 7.20±1.83 mL/sec in ICA, 1.36±0.55 to 2.33±1.31 mL/sec in VA, p < 0.05). The CVR was quantitatively higher in ICA than VA (slope of linear regression: 0.23 vs. 0.07 mL/sec/mmHg, p < 0.05). No statistically significant effect was observed in CVR between male and female (0.25 vs 0.20 mL/sec/mmHg in ICA, 0.09 vs 0.11 mL/sec/mmHg in VA, p > 0.05). Conclusions The principal finding in this investigation validated the modulation of CBF by CO₂. Moreover, it has indicated that regional heterogeneity in hemodynamic response exists in the brain. This study provides scope to standardize the quantification of CVR prior to its clinical translation.

Keywords: cerebrovascular disease, neuroimaging, phase contrast MRI, cerebrovascular reactivity, carbon dioxide

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Authors: Zak Maas, Daniel Carson, Rachel McIntyre, Mark Omundsen, Teresa Holm

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Aim: After hemicolectomy a period of obligatory bowel dysfunction is expected, termed postoperative ileus (POI). Prolonged postoperative ileus (PPOI), typically four or more days, is associated with higher morbidity and extended inpatient stay. This leads to significant financial and resource-related burdens on healthcare systems. Several studies including a meta-analysis have compared rates of PPOI in left vs right hemicolectomy, which suggest that right-sided resections may be more likely to result in PPOI. Our study aims to further investigate whether significant differences in PPOI and obligatory POI exist between right versus extended right hemicolectomy. Methods: This is a retrospective review assessing rates of PPOI in patients who underwent right vs extended right hemicolectomy at Tauranga Hospital. Patients were divided and compared depending on approach (open versus laparoscopic) and acuity (acute versus elective). Exclusion criteria included synchronous major operations and patients preoperatively on parenteral nutrition. Primary outcome was PPOI as pre-defined in contemporary literature. Secondary outcomes were time to passage of flatus, passage of stool, toleration of oral diet and rate of complications. Results: There were 669 patients identified for analysis (507 laparoscopic vs 162 open; 194 acute vs 475 elective). Early analysis indicates rates of PPOI was significantly increased in patients undergoing extended right hemicolectomy. Factors including age, gender, ethnicity, preoperative haemaglobin, preoperative albumin and diagnosis of inflammatory bowel disease were examined by multivariate analysis to determine correlation with PPOI. Conclusion: PPOI is a common complication of hemicolectomy surgery. Higher rates of PPOI in extended right vs right hemicolectomy warrants further research into determining the cause. This study examines some other factors which may contribute to PPOI.

Keywords: hemicolectomy, colorectal, complications, postoperative ileus

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Authors: Michio Kurosu

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Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

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Authors: Ageliki I. Katsarou, Andriana C. Kaliora, Antonia Chiou, Apostolos Papalois, Nick Kalogeropoulos, Nikolaos K. Andrikopoulos

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Oxidative stress is a major mechanism underlying CVDs while inflammation, an intertwined process with oxidative stress, is also linked to CVDs. Extra virgin olive oil (EVOO) is widely known to play a pivotal role in CVD prevention and CVD reduction. However, in most studies, olive oil constituents are evaluated individually and not as part of the native food, hence potential synergistic effects as drivers of EVOO beneficial properties may be underestimated. In this study, EVOO lipidic and polar phenolics fractions were evaluated for their effect on inflammatory (TNF-alpha) and oxidation (malondialdehyde/MDA) markers, in cholesterol-fed rats. Thereat, oils with discernible lipidic profile and polar phenolic content were used. Wistar rats were fed on either a high-cholesterol diet (HCD) or a HCD supplemented with oils, either commercially available, i.e. EVOO, sunflower oil (SO), or modified as to their polar phenol content, i.e. phenolics deprived-EVOO (EVOOd), SO enriched with the EVOO phenolics (SOe). After 9 weeks of dietary intervention, heart and blood samples were collected. HCD induced dylipidemia shown by increase in serum total cholesterol, low-density lipoprotein cholesterol (LDL-c) and triacylglycerols. Heart tissue has been affected by dyslipidemia; oxidation was indicated by increase in MDA in cholesterol-fed rats and inflammation by increase in TNF-alpha. In both cases, this augmentation was attenuated in EVOO and SOe diets. With respect to oxidation, SO enrichment with the EVOO phenolics brought its lipid peroxidation levels as low as in EVOO-fed rats. This suggests that phenolic compounds may act as antioxidant agents in rat heart. A possible mechanism underlying this activity may be the protective effect of phenolics in mitochondrial membrane against oxidative damage. This was further supported by EVOO/EVOOd comparison with the former presenting lower heart MDA content. As for heart inflammation, phenolics naturally present in EVOO as well as phenolics chemically added in SO, exhibited quenching abilities in heart TNF-alpha levels of cholesterol-fed rats. TNF-alpha may have played a causative role in oxidative stress induction while the opposite may have also happened, hence setting up a vicious cycle. Overall, diet supplementation with EVOO or SOe attenuated hypercholesterolemia-induced increase in MDA and TNF-alpha in Wistar rat hearts. This is attributed to phenolic compounds either naturally existing in olive oil or as fortificants in seed oil.

Keywords: extra virgin olive oil, hypercholesterolemic rats, MDA, polar phenolics, TNF-alpha

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Authors: Asma Naseer Cheema, Attya Bhatti, Jabar Ali, John Peter

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Background: High cholesterol levels, endothelial dysfunction, inefficient coagulation cascade and hyper inflammatory response all are the basis of coronary artery disease (CAD). Several studies are carried out to see the genetic influence of these factors on disease outcome. Objective: The objective of our study was to see the association of 10 putative loci with coronary artery disease in our population. Materials & Methods: We screened our population for 10 putative loci of CAD showing significant association (p < 5x10-8) with candidate genes (regulating the cholesterol metabolism, endothelial function, coagulation cascade and inflammatory response of body). Hardy-Weinberg equilibrium and linkage disequilibrium in cases and controls s were estimated separately. Approximately 5-10 ng of dried DNA in 384 well plate format was used to genotype each sample on the Sequenom iPLEX assay at University of Pittsburgh Genomics and Proteomics Core Laboratories. It was built on single-base primer extension with the MALDI-TOF MS detection possessing high sensitivity and specificity. The SNPs were genotyped through Taqman assay. Hardy Weinberg test was applied. The 10 SNPs were selected as genetic markers for this study (rs579459, rs1561198, rs2954029, rs1122608, rs17114036, rs9515203, rs10947789, rs7173743, rs2895811, rs2075650). Results: Mean age of the patient was 52 ± 11 years. Blood pressure and positive family history was found a significant risk factor for CAD. None of the selected SNPs showed significant association with coronary artery disease in our population (p>0.05). Conclusion: rs579459, rs1561198, rs2954029, rs1122608, rs17114036, rs9515203, rs10947789, rs7173743, rs2895811, rs2075650 are not significant genetic markers for CAD in our population.

Keywords: CAD, genetic markers, loci, risk factors

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Authors: Eftychia Pappa, Heleni Vastardis, Christos Rahiotis, Andriani Vazaiou

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The aim of this study was to evaluate the prevalence of dry-mouth symptoms (xerostomia) and compare it with alterations in salivary characteristics of children and adolescents with type 1 diabetes (DM1), as measured with the use of chair-side saliva tests. This study also investigated the possible association between salivary dysfunction and incidence of caries, in relation to the level of metabolic control. A cross-sectional study was performed on young patients (6-18 years old) allocated among 3 groups: 40 patients poorly-controlled (DM1-A, HbA1c>8%), 40 well-controlled (DM1-B, HbA1c≤8%) and 40 age- and sex-matched healthy controls. The study was approved by the Research Ethics Committee of University of Athens and the parents signed written informed consent. All subjects were examined for dental caries, oral hygiene and salivary factors. Assessments of salivary function included self-reported xerostomia, quantification of resting and stimulated whole saliva flow rates, pH values, buffering capacity and saliva’s viscosity. Salivary characteristics were evaluated with the use of GC Saliva Check Buffer (3Μ ESPE). Data were analysed by chi-square and Kruskal-Wallis tests. Subjects with diabetes reported xerostomia more frequently than healthy controls (p<0.05). Unstimulated salivary flow rate and pH values remained significantly lower in DM1-A compared to DM1-B and controls. Low values of resting salivary flow rate were associated with a higher prevalence of dental caries in children and adolescents with poorly-controlled DM1 (p<0.05). The results suggested that diabetes-induced alterations in salivary characteristics are indicative of higher caries susceptibility of diabetics and chair-side saliva tests are a useful tool for the evaluation of caries risk assessment.

Keywords: caries risk assessment, saliva diagnostic tests, type 1 diabetes, xerostomia

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Authors: Ediati Budi Cahyono, Triana Hertiani, Nauval Arrazy Asawimanda, Wahyu Puji Pratomo

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Background: Doxorubicin is widely used as a chemotherapeutic drug despite having many side effects. It may cause macrophage dysfunction and decreasing proliferation of lymphocyte. Noni (Morinda citrifolia) fruit which has rich of polysaccharide content has potential as antitumor and immunostimulant effect. The isolation of polysaccharide from Noni fruit has been optimized according to four different methods based on macrophage and lymphocyte activities. We found the highest polysaccharide content from one of the four methods isolation. A method of polysaccharide isolation which has the highest immunostimulant effect was used for further observation as co-chemotherapy. The aim of the study: was to evaluate the isolated polysaccharide from the method of choice as co-chemotherapy of doxorubicin for the growth of Vero, He-La, and T47D cell lines in vitro. The method: in vitro growth assay of Vero, He-La, and T47D cell lines was done using MTT-reduction method, and apoptosis test was done by double staining method to evaluate the induction apoptotic effect of the combination. Every group was treated with doxorubicin and isolated polysaccharide from method of choice with 4 variances of concentrations (25 µg/ml, 50 µg/ml, 100 µg/ml and 200 µg/ml) a long with negative control (doxorubicin only) and normal control (without doxorubicin or polysaccharide administration). Results: The combination of polysaccharide fraction in the concentration of 100μg/ml with 2μmol of doxorubicin against He-La and T47D cell lines influenced the highest cytotoxic effect by suppressing cell viability comparing with doxorubicin only. The combination of polysaccharide fraction in the concentration of 100μg/ml with 2μmol of doxorubicin-induced apoptotic effect the He-La cell line comparing with doxorubicin only. The result of the study: it can be concluded that the combination of polysaccharide fraction and doxorubicin effect more selective toward He-La and T47D cell lines than to Vero cell line. It can be suggested isolated polysaccharide from the method of choice has co-chemotherapy activity against doxorubicin.

Keywords: polysaccharide, noni fruit, doxorubicin, cancer cell lines, vero cell line

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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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Authors: Kinjal H. Shah, Piyush M. Patel

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Diabetes mellitus is considered to be a serious endocrine syndrome. Synthetic hypoglycemic agents can produce serious side effects including hematological effects, coma, and disturbances of the liver and kidney. In addition, they are not suitable for use during pregnancy. In recent years, there have been relatively few reports of short-term side effects or toxicity due to sulphonylureas. Published figures and frequency of side effects in large series of patient range from about 1 to 5%, with symptoms severe enough to lead to the withdrawal of the drug in less than 1 to 2%. Adverse effects, in general, have been of the following type: allergic skin reactions, gastrointestinal disturbances, blood dyscrasias, hepatic dysfunction, and hypoglycemia. The associated disadvantages with insulin and oral hypoglycemic agents have led to stimulation in the research for locating natural resources showing antidiabetic activity and to explore the possibilities of using traditional medicines with proper chemical and pharmacological profiles. Literature survey reveals that the inhabitants of Abbottabad district of Pakistan use the dried leaf powder along with table salt and water orally for treating diabetes, skin allergy, wounds and as a blood purifier, where they pronounced the plant locally as ‘Nem.' The detailed phytochemical investigation of the Cedrela toona Roxb. leaves for antidiabetic activity has not been documented. Hence, there is a need for phytochemical investigation of the leaves for antidiabetic activity. The collection of fresh leaves and authentification followed by successive extraction, phytochemical screening, and testing of antidiabetic activity. The blood glucose level was reduced maximum in ethanol extract at 5th and 7th h after treatment. Blood glucose was depressed by 8.2% and 10.06% in alloxan – induced diabetic rats after treatment which was comparable to the standard drug, Glibenclamide. This may be due to the activation of the existing pancreatic cells in diabetic rats by the ethanolic extract.

Keywords: antidiabetic, Cedrela toona Roxb., phytochemical screening, blood glucose

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Authors: Elisa Maître

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The redeployment of tram networks in French cities has considerably modified public spaces and the way citizens use them. Above and beyond the image that trams have of contributing to the sustainable urban development, the question of safety for users in these spaces has not been studied much. This study is based on an analysis of use of public spaces laid out for trams, from the standpoint of legibility and safety concerns. The study also examines to what extent the complexity of the design process, with many interactions between numerous and varied players in this process has a role in the genesis of these problems. This work is mainly based on the analysis of links between the uses of these re-designed public spaces (through observations, interviews of users and accident studies) and the analysis of the design conditions and processes of the projects studied (mainly based on interviews with the actors of these projects). Practical analyses were based three points of view: that of the planner, that of the user (based on observations and interviews) and that of the road safety expert. The cities of Montpellier, Marseille and Nice are the three fields of study on which the demonstration of this thesis is based. On part, the results of this study allow showing that the insertion of tram poses some problems complication of public areas of French cities. These complications related to the restructuring of public spaces for the tram, create difficulties of use and safety concerns. On the other hand, interviews depth analyses, fully transcribed, have led us to develop particular dysfunction scenarios in the design process. These elements lead to question the way the legibility and safety of these new forms of public spaces are taken into account. Then, an in-depth analysis of the design processes of public spaces with trams systems would also be a way of better understanding the choices made, the compromises accepted, and the conflicts and constraints at work, weighing on the layout of these spaces. The results presented concerning the impact that spaces laid out for trams have on the difficulty of use, suggest different possibilities for improving the way in which safety for all users is taken into account in designing public spaces.

Keywords: public spaces, road layout, users, design process of urban projects

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Authors: Mitra Assadi, Md. Faan

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Background: Autism Spectrum Disorder (ASD) in a common neurodevelopmental disorder with limited pharmacological interventions. Transcranial Magnetic Stimulation (rTMS) has produced promising results in ASD, although there is no consensus regarding optimal targets or stimulation paradigms. A prevailing theory in ASD attributes the core deficits to dysfunction of the mirror neurons located in the inferior parietal lobule (IPL) and inferior frontal gyrus (IFG). Methods: Thus far, 11 subjects with ASD, 10 boys and 1 girl with the mean age of 13.36 years have completed the study by receiving 10 session of high frequency rTMS to the IPL. The subjects were randomized to receive stimulation on the left or right IPL and sham stimulation to the opposite side. The outcome measures included the Social Responsiveness Scale – Second Edition (SRS-2) and Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency task. Results: None of the 11 subjects experienced any adverse effects. The rTMS did not produce any improvement in verbal fluency, nor there was any statistically significant difference between the right versus left sided stimulation. Analysis of social awareness on SRS-2 (SRS-AWR) indicated a close to significant effect of the treatment with a small to medium effect size. After removing a single subject with Level 3 ASD, we demonstrated a close to significant improvement on SRS-AWR with a large effect size. The analysis of the data 3-month post TMS demonstrated return of the SRS-AWR values to baseline. Conclusion: This preliminary analysis of the 11 subjects who have completed our study thus far shows a favorable response to high frequency rTMS stimulation of the mirror neurons/IPL on social awareness. While the decay of the response noted during the 3-month follow-up may be considered a limitation of rTMS, the presence of the improvement, especially the effect size despite the small sample size, is indicative of the efficacy of this technique.

Keywords: rTMS, autism, scoial cognition, mirror neurons

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Authors: Peter David Reiss

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The concept of the psychosis prodrome has allowed for the identification of adolescent and young adult patients who have a significantly elevated risk of developing schizophrenia spectrum disorders. A number of different interventions have been tested in order to prevent or delay progression of symptoms. To date, there has been no consistent meta-analytical evidence to support efficacy of antipsychotic treatment for patients in the prodromal state, and their use remains therefore inconclusive. Although antipsychotics may manage symptoms transiently, they have not been found to prevent or delay onset of psychotic disorders. Furthermore, pharmacological intervention in high-risk individuals remains controversial, because of the antipsychotic side effect profile in a population in which only about 20 to 35 percent will eventually convert to psychosis over a two-year period, with even after two years conversion rates not exceeding 30 to 40 percent. This general estimate is additionally problematic, in that it ignores the fact that there is significant variation in individual risk among clinical high-risk cases. The current lack of reliable tests for at-risk patients makes it difficult to justify individual treatment decisions. Preventive treatment should ideally be dictated by an individual’s risk while minimizing potentially harmful medication exposure. This requires more accurate predictive assessments by using valid and accessible prognostic markers. The following will compare prediction and risk modification potential of behavioral biomarkers such as disturbances of basic sense of self and emotion awareness, neurocognitive biomarkers such as attention, working and declarative memory, and neurophysiological biomarkers such as glutamatergic abnormalities and NMDA receptor dysfunction. Identification of robust biomarkers could therefore not only provide more reliable means of psychosis prediction, but also help test and develop new clinical interventions targeted at the prodromal state.

Keywords: at-risk mental state, biomarkers, glutamatergic system, NMDA receptor, psychosis prodrome, schizophrenia

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Authors: Afsaneh Soltani, Zahra Mohajer

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Migraine is one of the most common chronic neurological diseases. Migraines affect different aspects of life. Severe migraine headaches lead to dysfunction, a reduced presence at work, and decreased ability to think and make decisions. Non-pharmacological treatments play a very important role in controlling and preventing migraine headaches. A healthy lifestyle helps control migraine headaches. Migraine headaches can be reduced by following these steps: Avoiding stress, eating regularly and avoiding hunger and thirst, avoiding stimulants such as chocolate, caffeine, and cigarettes, following a regular bedtime routine, or avoiding sleep deprivation. Exercise a lot, and do regular exercise (and prevent obesity). Non-pharmacological treatment is especially important in pregnant women and children because in these cases, medical treatments are not preferred due to the many side effects. Exercise is one of the most effective and uncomplicated non-pharmacological alternatives in the treatment of migraine headaches. Exercising for episodic migraines is a safe, effective, and promising complementary treatment option. Numerous studies have shown that aerobic exercise reduces the severity and duration of migraine headaches. Effective aerobic exercise includes cycling and brisk walking. Exercise improves the quality of life and reduces the use of medication in people with migraines. Patients who exercise have fewer migraine days, resulting in better personal, social, and occupational performance. Several studies have shown that pain intensity and frequency in patients who exercise regularly decreased significantly after exercise compared to controls who did not exercise. According to a study, regular exercise reduces the levels of interleukins, especially IL-12P70, which reduces anxiety and reduces the number of days of migraine in patients. An article has shown that endurance exercise reduces the number of migraine days and also increases cerebrovascular health in migraine patients. According to studies, the minimum duration of exercise to achieve a positive effect of exercise in patients with migraine is 3 months (12 weeks) and 40 minutes three times a week.

Keywords: exercise, headache, migraine, physical activity

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