Search results for: insulin analogue
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 466

Search results for: insulin analogue

46 Evaluation of Vitamin D Levels in Obese and Morbid Obese Children

Authors: Orkide Donma, Mustafa M. Donma

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Obesity may lead to growing serious health problems throughout the world. Vitamin D appears to play a role in cardiovascular and metabolic health. Vitamin D deficiency may add to derangements in human metabolic systems, particularly those of children. Childhood obesity is associated with an increased risk of chronic and sophisticated diseases. The aim of this study is to investigate associations as well as possible differences related to parameters affected by obesity and their relations with vitamin D status in obese (OB) and morbid obese (MO) children. This study included a total of 78 children. Of them, 41 and 37 were OB and MO, respectively. WHO BMI-for age percentiles were used for the classification of obesity. The values above 99 percentile were defined as MO. Those between 95 and 99 percentiles were included into OB group. Anthropometric measurements were recorded. Basal metabolic rates (BMRs) were measured. Vitamin D status is determined by the measurement of 25-hydroxy cholecalciferol [25- hydroxyvitamin D3, 25(OH)D] using high-performance liquid chromatography. Vitamin D status was evaluated as deficient, insufficient and sufficient. Values < 20.0 ng/ml, values between 20-30 ng/ml and values > 30.0 ng/ml were defined as vitamin D deficient, insufficient and sufficient, respectively. Optimal 25(OH)D level was defined as ≥ 30 ng/ml. SPSSx statistical package program was used for the evaluation of the data. The statistical significance degree was accepted as p < 0.05. Mean ages did not differ between the groups. Significantly increased body mass index (BMI), waist circumference (C) and neck C as well as significantly decreased fasting blood glucose (FBG) and vitamin D values were observed in MO group (p < 0.05). In OB group, 37.5% of the children were vitamin D deficient, and in MO group the corresponding value was 53.6%. No difference between the groups in terms of lipid profile, systolic blood pressure (SBP), diastolic blood pressure (DBP) and insulin values was noted. There was a severe statistical significance between FBG values of the groups (p < 0.001). Important correlations between BMI, waist C, hip C, neck C and both SBP as well as DBP were found in OB group. In MO group, correlations only with SBP were obtained. In a similar manner, in OB group, correlations were detected between SBP-BMR and DBP-BMR. However, in MO children, BMR correlated only with SBP. The associations of vitamin D with anthropometric indices as well as some lipid parameters were defined. In OB group BMI, waist C, hip C and triglycerides (TRG) were negatively correlated with vitamin D concentrations whereas none of them were detected in MO group. Vitamin D deficiency may contribute to the complications associated with childhood obesity. Loss of correlations between obesity indices-DBP, vitamin D-TRG, as well as relatively lower FBG values, observed in MO group point out that the emergence of MetS components starts during obesity state just before the transition to morbid obesity. Aside from its deficiency state, associations of vitamin D with anthropometric measurements, blood pressures and TRG should also be evaluated before the development of morbid obesity.

Keywords: children, morbid obesity, obesity, vitamin D

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45 Neuro-Epigenetic Changes on Diabetes Induced-Synaptic Fidelity in Brain

Authors: Valencia Fernandes, Dharmendra Kumar Khatri, Shashi Bala Singh

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Background and Aim: Epigenetics are the inaudible signatures of several pathological processes in the brain. This study understands the influence of DNA methylation, a major epigenetic modification, in the prefrontal cortex and hippocampus of the diabetic brain and its notable effect on the cellular chaperones and synaptic proteins. Method: Chronic high fat diet and STZ-induced diabetic mice were studied for cognitive dysfunction, and global DNA methylation, as well as DNA methyltransferase (DNMT) activity, were assessed. Further, the cellular chaperones and synaptic proteins were examined using DNMT inhibitor, 5-aza-2′-deoxycytidine (5-aza-dC)-via intracerebroventricular injection. Moreover, % methylation of these synaptic proteins were also studied so as to correlate its epigenetic involvement. Computationally, its interaction with the DNMT enzyme were also studied using bioinformatic tools. Histological studies for morphological alterations and neuronal degeneration were also studied. Neurogenesis, a characteristic marker for new learning and memory formation, was also assessed via the BrdU staining. Finally, the most important behavioral studies, including the Morris water maze, Y maze, passive avoidance, and Novel object recognition test, were performed to study its cognitive functions. Results: Altered global DNA methylation and increased levels of DNMTs within the nucleus were confirmed in the cortex and hippocampus of the diseased mice, suggesting hypermethylation at a genetic level. Treatment with AzadC, a global DNA demethylating agent, ameliorated the protein and gene expression of the cellular chaperones and synaptic fidelity. Furthermore, the methylation analysis profile showed hypermethylation of the hsf1 protein, a master regulator for chaperones and thus, confirmed the epigenetic involvement in the diseased brain. Morphological improvements and decreased neurodegeneration, along with enhanced neurogenesis in the treatment group, suggest that epigenetic modulations do participate in learning and memory. This is supported by the improved behavioral test battery seen in the treatment group. Conclusion: DNA methylation could possibly accord in dysregulating the memory-associated proteins at chronic stages in type 2 diabetes. This could suggest a substantial contribution to the underlying pathophysiology of several metabolic syndromes like insulin resistance, obesity and also participate in transitioning this damage centrally, such as cognitive dysfunction.

Keywords: epigenetics, cognition, chaperones, DNA methylation

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44 Comparative Study of Active Release Technique and Myofascial Release Technique in Patients with Upper Trapezius Spasm

Authors: Harihara Prakash Ramanathan, Daksha Mishra, Ankita Dhaduk

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Relevance: This qualitative study will educate the clinician in putting into practice the advanced method of movement science in restoring the function. Purpose: The purpose of this study is to compare the effectiveness of Active Release Technique and myofascial release technique on range of motion, neck function and pain in patients with upper trapezius spasm. Methods/Analysis: The study was approved by the institutional Human Research and Ethics committee. This study included sixty patients of age group between 20 to 55 years with upper trapezius spasm. Patients were randomly divided into two groups receiving Active Release Technique (Group A) and Myofascial Release Technique (Group B). The patients were treated for 1 week and three outcome measures ROM, pain and functional level were measured using Goniometer, Visual analog scale(VAS), Neck disability Index Questionnaire(NDI) respectively. Paired Sample 't' test was used to compare the differences of pre and post intervention values of Cervical Range of motion, Neck disability Index, Visual analog scale of Group A and Group B. Independent't' test was used to compare the differences between two groups in terms of improvement in cervical range of motion, decrease in visual analogue scale(VAS), decrease in Neck disability index score. Results: Both the groups showed statistically significant improvements in cervical ROM, reduction in pain and in NDI scores. However, mean change in Cervical flexion, cervical extension, right side flexion, left side flexion, right side rotation, left side rotation, pain, neck disability level showed statistically significant improvement (P < 0. 05)) in the patients who received Active Release Technique as compared to Myofascial release technique. Discussion and conclusions: In present study, the average improvement immediately post intervention is significantly greater as compared to before treatment but there is even more improvement after seven sessions as compared to single session. Hence, this proves that several sessions of Manual techniques are necessary to produce clinically relevant results. Active release technique help to reduce the pain threshold by removing adhesion and promote normal tissue extensibility. The act of tensioning and compressing the affected tissue both with digital contact and through the active movement performed by the patient can be a plausible mechanism for tissue healing in this study. This study concluded that both Active Release Technique (ART) and Myofascial release technique (MFR) are equally effective in managing upper trapezius muscle spasm, but more improvement can be achieved by Active Release Technique (ART). Impact and Implications: Active Release Technique can be adopted as mainstay of treatment approach in treating trapezius spasm for faster relief and improving the functional status.

Keywords: trapezius spasm, myofascial release, active release technique, pain

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43 The Evaluation of a Novel Cardiac Index derived from Anthropometric and Biochemical Parameters in Pediatric Morbid Obesity and Metabolic Syndrome

Authors: Mustafa Metin Donma

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Metabolic syndrome (MetS) components are noteworthy among children with obesity and morbid obesity because they point out the cases with MetS, which have the great tendency to severe health problems such as cardiovascular diseases both in childhood and adulthood. In clinical practice, considerable efforts are being observed to bring into the open the striking differences between morbid obese cases and those with MetS findings. The most privileged aspect is concerning cardiometabolic features. The aim of this study was to derive an index which behaves different in children with and without MetS from the cardiac point of view. For the purpose, aspartate transaminase (AST), a cardiac enzyme still being used independently to predict cardiac-related problems, was used. One hundred and twenty four children were recruited from the outpatient clinic of Department of Pediatrics in Tekirdag Namik Kemal University, Faculty of Medicine. Forty-three children with normal body mass index, forty-one and forty morbid obese (MO) children with MetS and without the characteristic features of MetS, respectively, were included in the study. Weight, height, waist circumference (WC), hip C (HC), head C (HdC), neck C (NC), systolic and diastolic blood pressure values were measured and recorded. Body mass index and anthropometric ratios were calculated. Fasting blood glucose (FBG), insulin (INS), triglycerides (TRG), high density lipoprotein cholesterol (HDL-C) analyses were performed. The values for AST, alanin transaminase (ALT) and AST/ALT were obtained. Advanced Donma cardiac index (ADCI) values were calculated. The formula for the index was [(TRG/HDL-C) * (INS/FBG)] * [(WC+HC)/Height] * [(HdC+NC)/Height]. Statistical evaluations including correlation analysis were done by a statistical package program. The statistical significance degree was accepted as p<0.05. The index, ADCI, was developed from both anthropometric and biochemical parameters. All anthropometric measurements except weight were included in the equation. Besides all biochemical parameters concerning MetS components were also added. This index was tested in each of three groups. Its performance was compared with the performance of cardiometabolic index (CMI). It was also checked whether it was compatible with AST activity. The performance of ADCI was better than that of CMI. Instead of double increase, the increase of three times was observed in children with MetS compared to MO children. The index was correlated with AST in MO group and with AST/ALT in MetS group. In conclusion, this index was superior in discovering cardiac problems in MO and in diagnosing MetS in MetS groups. It was also arbiter to point out cardiovascular and MetS aspects among the groups.

Keywords: aspartate transaminase, cardiac, children, index, obesity

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42 Benefits of The ALIAmide Palmitoyl-Glucosamine Co-Micronized with Curcumin for Osteoarthritis Pain: A Preclinical Study

Authors: Enrico Gugliandolo, Salvatore Cuzzocrea, Rosalia Crupi

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Osteoarthritis (OA) is one of the most common chronic pain conditions in dogs and cats. OA pain is currently viewed as a mixed phenomenon involving both inflammatory and neuropathic mechanisms at the peripheral (joint) and central (spinal and supraspinal) levels. Oxidative stress has been implicated in OA pain. Although nonsteroidal anti-inflammatory drugs are commonly prescribed for OA pain, they should be used with caution in pets because of adverse effects in the long term and controversial efficacy on neuropathic pain. An unmet need remains for safe and effective long-term treatments for OA pain. Palmitoyl-glucosamine (PGA) is an analogue of the ALIAamide palmitoylethanolamide, i.e., a body’s own endocannabinoid-like compound playing a sentinel role in nociception. PGA, especially in the micronized formulation, was shown safe and effective in OA pain. The aim of this study was to investigate the effect of a co-micronized formulation of PGA with the natural antioxidant curcumin (PGA-cur) on OA pain. Ten Sprague-Dawley male rats were used for each treatment group. The University of Messina Review Board for the care and use of animals authorized the study. On day 0, rats were anesthetized (5.0% isoflurane in 100% O2) and received intra-articular injection of MIA (3 mg in 25 μl saline) in the right knee joint, with the left being injected an equal volume of saline. Starting the third day after MIA injection, treatments were administered orally three times per week for 21 days, at the following doses: PGA 20 mg/kg, curcumin 10 mg/kg, PGA-cur (2:1 ratio) 30 mg/kg. On day 0 and 3, 7, 14 and 21 days post-injection, mechanical allodynia was measured using a dynamic plantar Von Frey hair aesthesiometer and expressed as paw withdrawal threshold (PWT) and latency (PWL). Motor functional recovery of the rear limb was evaluated on the same time points by walking track analysis using the sciatic functional index. On day 21 post-MIA injection, the concentration of the following inflammatory and nociceptive mediators was measured in serum using commercial ELISA kits: tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), nerve growth factor (NGF) and matrix metalloproteinase-1-3-9 (MMP-1, MMP-3, MMP-9). The results were analyzed by ANOVA followed by Bonferroni post-hoc test for multiple comparisons. Micronized PGA reduced neuropathic pain, as shown by the significant higher PWT and PWL values compared to vehicle group (p < 0.0001 for all the evaluated time points). The effect of PGA-cur was superior at all time points (p < 0.005). PGA-cur restored motor function already on day 14 (p < 0.005), while micronized PGA was effective a week later (D21). MIA-induced increase in the serum levels of all the investigated mediators was inhibited by PGA-cur (p < 0.01). PGA was also effective, except on IL-1 and MMP-3. Curcumin alone was inactive in all the experiments at any time point. The encouraging results suggest that PGA-cur may represent a valuable option in OA pain management and warrant further confirmation in well-powered clinical trials.

Keywords: ALIAmides, curcumin, osteoarthritis, palmitoyl-glucosamine

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41 Effect of Low Calorie Sweeteners on Chemical, Sensory Evaluation and Antidiabetic of Pumpkin Jam Fortified with Soybean

Authors: Amnah M. A. Alsuhaibani, Amal N. Al-Kuraieef

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Introduction: In the recent decades, production of low-calorie jams is needed for diabetics that comprise low calorie fruits and low calorie sweeteners. Object: the research aimed to prepare low calorie formulated pumpkin jams (fructose, stevia and aspartame) incorporated with soy bean and evaluate the jams through chemical analysis and sensory evaluation after storage for six month. Moreover, the possible effect of consumption of low calorie jams on diabetic rats was investigated. Methods: Five formulas of pumpkin jam with different sucrose, fructose, stevia and aspartame sweeteners and soy bean were prepared and stored at 10 oC for six month compared to ordinary pumpkin jam. Chemical composition and sensory evaluation of formulated jams were evaluated at zero time, 3 month and 6 month of storage. The best three acceptable pumpkin jams were taken for biological study on diabetic rats. Rats divided into group (1) served as negative control and streptozotocin induce diabetes four rat groups that were positive diabetic control (group2), rats fed on standard diet with 10% sucrose soybean jam, fructose soybean jam and stevia soybean jam (group 3, 4&5), respectively. Results: The content of protein, fat, ash and fiber were increased but carbohydrate was decreased in low calorie formulated pumpkin jams compared to ordinary jam. Production of aspartame soybean pumpkin jam had lower score of all sensory attributes compared to other jam then followed by stevia soybean Pumpkin jam. Using non nutritive sweeteners (stevia & aspartame) with soybean in processing jam could lower the score of the sensory attributes after storage for 3 and 6 months. The highest score was recorded for sucrose and fructose soybean jams followed by stevia soybean jam while aspartame soybean jam recorded the lowest score significantly. The biological evaluation showed a significant improvement in body weight and FER of rats after six weeks of consumption of standard diet with jams (Group 3,4&5) compared to Group1. Rats consumed 10% low calorie jam with nutrient sweetener (fructose) and non nutrient sweetener (stevia) soybean jam (group 4& 5) showed significant decrease in glucose level, liver function enzymes activity, and liver cholesterol & total lipids in addition of significant increase of insulin and glycogen compared to the levels of group 2. Conclusion: low calorie pumpkin jams can be prepared by low calorie sweeteners and soybean and also storage for 3 months at 10oC without change sensory attributes. Consumption of stevia pumpkin jam fortified with soybean had positive health effects on streptozoticin induced diabetes in rats.

Keywords: pumpkin jam, HFCS, aspartame, stevia, storage

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40 Rice Tablet Poisoning in Iran

Authors: Somayeh Khanjani, Samaneh Nabavi, Shirin Jalili

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Aluminum phosphide (ALP) is an inorganic phosphide used to control insects and is a highly effective insecticide and rodenticide used frequently to protect stored grain. Acute poisoning with this compound is common in some countries including India and Iran, and is a serious health problem. In Iran it was known as "rice tablet", for its use to preserve rice. Two kinds of rice tablets one being herbal while other containing 3g aluminum phosphide (AlP) are available for use in Iranian households to protect stored food grains from pests and rodents. The toxicity of Aluminum phosphide is attributed to the liberation of phosphine gas in contact with water or weak acid and is the major cause of poisoning and deaths. Rice tablet (Aluminum Phosphid) poisoning may be associated with serious and sometimes incurable complications. In 61.3% of patients were shown uniform ingestion. Vomiting was the most common symptoms reported by 96.4% patients. Agitation was reported in 36.9% and felling of thirsty in 27.9 %. Although many complications such as Hypotension, Adult Respiratory Distress Syndrome (ARDS), Acute Renal Failure (ARF) AND Multi Organ Failure (MOF) were the common complications observed in these patients, but the most lethal complication was Cardiac Arrhythmias occurred in 36.9% of cases. Abdominal pain in 31.4% of the patients, nausea in 79.4% of the patients and 41.1% of the patients showed metabolic acidosis. Suicidal intention was the most common cause of poisoning leading to deaths in 18.6% of the patients. Aluminum phosphide can cause either elevation, decrease or no change in electrolytes, bicarbonate and blood glucose level. The possible mechanism for changes in blood glucose levels are complex and depend on the balance of factors which increase its concentration and those which reduce it. AlP poisoning has been postulated to stimulate cortisol which leads to increasing blood level of cortisol, also it may cause stimulation of glucagon, and Adrenaline secretion; in addition, it can inhibit insulin synthesis which may lead to hyperglycemia. Another suggested mechanism of hyperglycemia is rennin activity in some cases, an increase in magnesium level of plasma and that of tissues, and high phosphate level. Although hyperglycemia is most frequent in this poisoning and also is known as a marker of poor prognostic, hypoglycemia in aluminum phosphide poisoning is a rare finding which may be so dangerous. Patients showed sever hypotension and sever acidosis in addition to sever hypoglycemia. The presenting features of AlP intoxication are rapid onset of shock, severe metabolic acidosis, cardiac dysrhythmias and adult respiratory distress syndrome (ARDS).

Keywords: aluminum phosphide (ALP), rice tablet, poisoning, phosphine gas

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39 Effect of Fast and Slow Tempo Music on Muscle Endurance Time

Authors: Rohit Kamal, Devaki Perumal Rajaram, Rajam Krishna, Sai Kumar Pindagiri, Silas Danielraj

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Introduction: According to WHO, Global health observatory at least 2.8 million people die each year because of obesity and overweight. This is mainly because of the adverse metabolic effects of obesity and overweight on blood pressure, lipid profile especially cholesterol and insulin resistance. To achieve optimum health WHO has set the BMI in the range of 18.5 to 24.9 kg/m2. Due to modernization of life style, physical exercise in the form of work is no longer a possibility and hence an effective way to burn out calories to achieve the optimum BMI is the need of the hour. Studies have shown that exercising for more than 60 minutes /day helps to maintain the weight and to reduce the weight exercise should be done for 90 minutes a day. Moderate exercise for about 30 min is essential for burning up of calories. People with low endurance fail to perform even the low intensity exercise for minimal time. Hence, it is necessary to find out some effective method to increase the endurance time. Methodology: This study was approved by the Institutional Ethical committee of our college. After getting written informed consent, 25 apparently healthy males between the age group 18-20 years were selected. Subjects are with muscular disorder, subjects who are Hypertensive, Diabetes, Smokers, Alcoholics, taking drugs affecting the muscle strength. To determine the endurance time: Maximum voluntary contraction (MVC) was measured by asking the participants to squeeze the hand grip dynamometer as hard as possible and hold it for 3 seconds. This procedure was repeated thrice and the average of the three reading was taken as the maximum voluntary contraction. The participant was then asked to squeeze the dynamometer and hold it at 70% of the maximum voluntary contraction while hearing fast tempo music which was played for about ten minutes then the participant was asked to relax for ten minutes and was made to hold the hand grip dynamometer at 70% of the maximum voluntary contraction while hearing slow tempo music. To avoid the bias of getting habituated to the procedure the order of hearing for the fast and slow tempo music was changed. The time for which they can hold it at 70% of MVC was determined by using a stop watch and that was taken as the endurance time. Results: The mean value of the endurance time during fast and slow tempo music was compared in all the subjects. The mean MVC was 34.92 N. The mean endurance time was 21.8 (16.3) seconds with slow tempo music which was more then with fast tempo music with which the mean endurance time was 20.6 (11.7) seconds. The preference was more for slow tempo music then for fast tempo music. Conclusion: Music when played during exercise by some unknown mechanism helps to increase the endurance time by alleviating the symptoms of lactic acid accumulation.

Keywords: endurance time, fast tempo music, maximum voluntary contraction, slow tempo music

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38 Foslip Loaded and CEA-Affimer Functionalised Silica Nanoparticles for Fluorescent Imaging of Colorectal Cancer Cells

Authors: Yazan S. Khaled, Shazana Shamsuddin, Jim Tiernan, Mike McPherson, Thomas Hughes, Paul Millner, David G. Jayne

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Introduction: There is a need for real-time imaging of colorectal cancer (CRC) to allow tailored surgery to the disease stage. Fluorescence guided laparoscopic imaging of primary colorectal cancer and the draining lymphatics would potentially bring stratified surgery into clinical practice and realign future CRC management to the needs of patients. Fluorescent nanoparticles can offer many advantages in terms of intra-operative imaging and therapy (theranostic) in comparison with traditional soluble reagents. Nanoparticles can be functionalised with diverse reagents and then targeted to the correct tissue using an antibody or Affimer (artificial binding protein). We aimed to develop and test fluorescent silica nanoparticles and targeted against CRC using an anti-carcinoembryonic antigen (CEA) Affimer (Aff). Methods: Anti-CEA and control Myoglobin Affimer binders were subcloned into the expressing vector pET11 followed by transformation into BL21 Star™ (DE3) E.coli. The expression of Affimer binders was induced using 0.1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG). Cells were harvested, lysed and purified using nickle chelating affinity chromatography. The photosensitiser Foslip (soluble analogue of 5,10,15,20-Tetra(m-hydroxyphenyl) chlorin) was incorporated into the core of silica nanoparticles using water-in-oil microemulsion technique. Anti-CEA or control Affs were conjugated to silica nanoparticles surface using sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo SMCC) chemical linker. Binding of CEA-Aff or control nanoparticles to colorectal cancer cells (LoVo, LS174T and HC116) was quantified in vitro using confocal microscopy. Results: The molecular weights of the obtained band of Affimers were ~12.5KDa while the diameter of functionalised silica nanoparticles was ~80nm. CEA-Affimer targeted nanoparticles demonstrated 9.4, 5.8 and 2.5 fold greater fluorescence than control in, LoVo, LS174T and HCT116 cells respectively (p < 0.002) for the single slice analysis. A similar pattern of successful CEA-targeted fluorescence was observed in the maximum image projection analysis, with CEA-targeted nanoparticles demonstrating 4.1, 2.9 and 2.4 fold greater fluorescence than control particles in LoVo, LS174T, and HCT116 cells respectively (p < 0.0002). There was no significant difference in fluorescence for CEA-Affimer vs. CEA-Antibody targeted nanoparticles. Conclusion: We are the first to demonstrate that Foslip-doped silica nanoparticles conjugated to anti-CEA Affimers via SMCC allowed tumour cell-specific fluorescent targeting in vitro, and had shown sufficient promise to justify testing in an animal model of colorectal cancer. CEA-Affimer appears to be a suitable targeting molecule to replace CEA-Antibody. Targeted silica nanoparticles loaded with Foslip photosensitiser is now being optimised to drive photodynamic killing, via reactive oxygen generation.

Keywords: colorectal cancer, silica nanoparticles, Affimers, antibodies, imaging

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37 Aframomum melegueta Improves Antioxidant Status of Type 2 Diabetes Rats Model

Authors: Aminu Mohammed, Shahidul Islam

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Aframomum melegueta K.Schum commonly known as Grains of Paradise has been a popularly used spice in most of the African food preparation. Available data have shown that ethyl acetate fraction from crude ethanolic extract exhibited α-amylase and α-glucosidase inhibitory actions, improved pancreatic β-cell damage and ameliorated insulin resistance in diabetic rats. Additionally, 6-gingerol, 6-shogaol, 6-paradol and oleanolic acid are shown to be the compounds responsible for the antidiabetic action of A. melegueta. However, detail antioxidant potential of this spice in a diabetic animal model has not yet been reported. Thus, the present study investigates the effect of oral consumption of A. melegueta fruit on the in vivo antioxidant status of type 2 diabetes (T2D) model of rats. T2D was induced in rats by feeding a 10% fructose solution ad libitum for two weeks followed by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight (bw)). The animals were orally administered with 150 (DAML) or 300 mg/kg bw (DAMH) of the fraction once daily for four weeks. Data were analyzed by using a statistical software package (SPSS for Windows, version 22, IBM Corporation, NY, USA) using Tukey’s-HSD multiple range post-hoc test. Values were considered significantly different at p < 0.05. According to the data, after four weeks of intervention, diabetic untreated animals showed significantly (p < 0.05) elevation of blood glucose levels. The levels of thiobarbituric acid reactive substances (TBARS) were observed to increase with concomitant reduction of reduced glutathione (GSH) levels in the serum and organs (liver, kidney, heart and pancreas) of diabetic untreated animals. The activities of endogenous antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and reductase) were greatly reduced in the serum and organs of diabetic untreated animals compared to the normal animals. These alterations were reverted to near-normal after the treatment of A. melegueta fruit in the treated groups (DAML & DAMH) within the study period, especially at the dose of 300 mg/kg bw. This potent antioxidant action may partly be attributed to the presence of the 6-Gingerol, 6-shogaol and 6-paradol are known to possess antioxidant action. The results of our study showed that A. melegueta intake improved the antioxidant status of T2D rats and therefore could be used to ameliorate the diabetes-induced oxidative damage.

Keywords: Aframomum melegueta, antioxidant, ethyl acetate extract, type 2 diabetes

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36 A Study of the Effect of Early and Late Meal Time on Anthropometric and Biochemical Parameters in Patients of Type 2 Diabetes

Authors: Smriti Rastogi, Narsingh Verma

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Background: A vast body of research exists on the use of oral hypoglycaemic drugs, insulin injections and the like in managing diabetes but no such research exists that has taken into consideration the parameter of time restricted meal intake and its positive effects in managing diabetes. The utility of this project is immense as it offers a solution to the woes of diabetics based on circadian rhythm and normal physiology of the human body. Method: 80 Diabetics, enrolled from the Out Patient Department of Endocrinology, KGMU (King George's Medical University) were randomly divided based on consent to early dinner TRM(time restricted meal) group or not (control group). Follow up was done at six months and 12 months for anthropometric measurement, height, weight, waist-hip ratio, neck size, fasting, postprandial blood sugar, HbA1c, serum urea, serum creatinine, and lipid profile. The patient was given a clear understanding of chronomedicine and how it affects their health. A single intervention was done - the timing of dinner was at or around 7 pm for TRM group. Result: 65% of TRM group and 40 %(non- TRM) had normal HbA1c after 12 months. HbA1c in TRM Group (first visit to second follow up) had a significant p value=0.017. A p value of <0.0001 was observed on comparing the values of blood sugar (fasting) in TRM Group from the first visit and second follow up. The values of blood sugar (postprandial) in TRM Group (first visit and second follow up) showed a p-value <0.0001 (highly significant). Values of the three parameters were non- significant in the control group. Hip size(First Visit to Second Follow Up) TRM Group showed a p-value = 0.0344 (Significant) (Difference between means=2.762 ± 1.261)Detailed results of the above parameters and a few newer ones will be presented at the conference. Conclusion: Time restricted meal intake in diabetics shows promise and is worth exploring further. Time Restricted Meal intake in Type 2 diabetics has a significant effect in controlling and maintaining HbA1c as the reduction in HbA1c value was very significant in the TRM group vs. the control group. Similar highly significant results were obtained in the case of fasting and postprandial values of blood sugar in the TRM group when compared to the control group. The effects of time restricted meal intake in diabetics show promise and are worth exploring further. It is one of the first studies which have been undertaken in Indian diabetics, although the initial data obtained is encouraging yet further research and study are required to corroborate results.

Keywords: chronomedicine, diabetes, endocrinology, time restricted meal intake

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35 Metformin Protects Cardiac Muscle against the Pro-Apoptotic Effects of Hyperglycaemia, Elevated Fatty Acid and Nicotine

Authors: Christopher R. Triggle, Hong Ding, Khaled Machaca, Gnanapragasam Arunachalam

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The antidiabetic drug, metformin, has been in clinical use for over 50 years and remains the first choice drug for the treatment of type two diabetes. In addition to its effectiveness as an oral anti-hyperglycaemic drug metformin also possesses vasculoprotective effects that are assumed to be secondary to its ability to reduce insulin resistance and control glycated hemoglobin levels; however, recent data from our laboratory indicate that metformin also has direct vasoprotective effects that are mediated, at least in part, via the anti-ageing gene, SIRT1. Diabetes is a major risk factor for the development of cardiovascular disease (CVD) and it is also well established that tobacco use further enhances the risk of CVD; however, it is not known whether treatment with metformin can offset the negative effects of diabetes and tobacco use on cardiac function. The current study was therefore designed to investigate 1: the effects of hyperglycaemia (HG) either alone or in the presence of elevated fatty acids (palmitate) and nicotine on the protein expression levels of the deacetylase sirtuin 1 (the protein product of SIRT1), anti-apoptotic Bcl-2, pro-apoptotic BIM and the pro-apoptotic, tumour suppressor protein, acetylated p53 in cardiomyocytes. 2: the ability of metformin to prevent the detrimental effects of HG, palmitate and nicotine on cardiomyocyte survival. Cell culture protocols were designed using a rat cardiomyocyte cell line, H9c2, either under normal glycaemic (NG) conditions of 5.5mM glucose, or hyperglycaemic conditions (HG) of 25mM glucose with, or without, added palmitate (250μM) or nicotine (1.0mM) for 24h. Immuno-blotting was used to detect the expression of sirtuin 1, Bcl-2, BIM, acetylated (Ac)-p53, p53 with β-actin used as the reference protein. Exposure to HG, palmitate, or nicotine alone significantly reduced expression of sirtuin1, Bcl-2 and raised the expression levels of acetylated p53 and BIM; however, the combination of HG, palmitate and nicotine had a synergistic effect to significantly suppress the expression levels of sirtuin 1 and Bcl-2, but further enhanced the expression of Ac-p53, and BIM. The inclusion of 1000μM, but not 50μM, metformin in the H9c2 cell culture protocol prevented the effects of HG, palmitate and nicotine on the pro-apoptotic pathways. Collectively these data indicate that metformin, in addition to its anti-hyperglycaemic and vasculoprotective properties, also has direct cardioprotective actions that offset the negative effects of hyerglycaemia, elevated free fatty acids and nicotine on cardiac cell survival. These data are of particular significance for the treatment of patients with diabetes who are also smokers as the inclusion of metformin in their therapeutic treatment plan should help reduce cardiac-related morbidity and mortality.

Keywords: apoptosis, cardiac muscle, diabetes, metformin, nicotine

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34 The Hypoglycaemic and Antioxidant Effects of Ethanolic Extract of Curcuma Longa Rhizomes Alone and with Two Pepper Adjuvants in Alloxan-Induced Diabetic Rats

Authors: J. O. Ezekwesili-Ofili, L. I. Okorafor, S. C. Nsofor

Abstract:

Diabetes mellitus is a carbohydrate metabolism disorder due to an absolute or relative deficiency of insulin secretion, action or both. Many known hypoglycaemic drugs are known to produce serious side effects. However, the search for safer and more effective agents has shifted to plant products, including foods and spices. One of such is the rhizome of Curcuma longa or turmeric, which is a spice with high medicinal value. A drawback in the use of C. longa is the poor bioavailability of curcumin, the active ingredient. It has been reported that piperine, an alkaloid present in peppers increases the bioavailability of curcumin. This work therefore investigated the hypoglycaemic and antioxidant effects of ethanolic extract of C. longa rhizomes, alone and with two pepper adjuvants in alloxan-induced diabetic rats. A total of 48 rats were divided into 6 groups of 8 rats each. Groups A–E were induced with diabetes using 150mg/kg body weight of alloxan monohydrate, while group F was normoglycaemic: Group A: Diabetic; fed with 400 mg/g body weight of turmeric extract; group B: Diabetic, fed with 400 mg/kg b. w. and 200mg/kg b. w of ethanolic extract of seeds of Piper guinensee; group C: Diabetic, fed with 400 mg/kg b. w. and 200 mg /kg b. w. of ethanolic extract of seeds of Capsicum annum var cameroun, group D: Diabetic, treated with standard drug, glibenclamide (0.3mg/kg body weight), group E: Diabetic; no treatment i.e. Positive control and group F: non diabetic, no treatment i.e. Negative control. Blood glucose levels were monitored for 14 days using a glucometer. The levels of the antioxidant enzymes; glutathione peroxidase, catalase and superoxide dismutase were also assayed in serum. The ethanolic extracts of C. longa rhizomes at the dose given (400 mg/kg b. w) significantly reduced the blood glucose levels of the diabetic rats (p<0.05) comparable to the standard drug. Co administration of extract of the peppers did not significantly increase the efficiency of the extract, although C. annum var cameroun showed greater effect, though not significantly. The antioxidant effect of the extract was significant in diabetic rats. The use of piperine-containing peppers enhanced the antioxidant effect. Phytochemical analyses of the ethanolic extract of C. longa showed the presence of alkaloids, flavonoids, steroids, saponins, tannins, glycosides, and terpenoids. These results suggest that the ethanolic extract of C. longa had antidiabetic with antioxidant effects and could thus be of benefit in the treatment and management of diabetes as well as ameliorate pro-oxidant effects that may lead to diabetic complications. However, while the addition of piperine did not affect the antidiabetic effect of C. longa, the antioxidant effect was greatly enhanced.

Keywords: antioxidant, Curcuma longa rhizome, hypoglycaemic, pepper adjuvants, piperine

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33 Serum Neurotrophins in Different Metabolic Types of Obesity

Authors: Irina M. Kolesnikova, Andrey M. Gaponov, Sergey A. Roumiantsev, Tatiana V. Grigoryeva, Alexander V. Laikov, Alexander V. Shestopalov

Abstract:

Background. Neuropathy is a common complication of obesity. In this regard, the content of neurotrophins in such patients is of particular interest. Neurotrophins are the proteins that regulate neuron survival and neuroplasticity and include brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). However, the risk of complications depends on the metabolic type of obesity. Metabolically unhealthy obesity (MUHO) is associated with a high risk of complications, while this is not the case with metabolically healthy obesity (MHO). Therefore, the aim of our work was to study the effect of the obesity metabolic type on serum neurotrophins levels. Patients, materials, methods. The study included 134 healthy donors and 104 obese patients. Depending on the metabolic type of obesity, the obese patients were divided into subgroups with MHO (n=40) and MUHO (n=55). In the blood serum, the concentration of BDNF and NGF was determined. In addition, the content of adipokines (leptin, asprosin, resistin, adiponectin), myokines (irisin, myostatin, osteocrin), indicators of carbohydrate, and lipid metabolism were measured. Correlation analysis revealed the relationship between the studied parameters. Results. We found that serum BDNF concentration was not different between obese patients and healthy donors, regardless of obesity metabolic type. At the same time, in obese patients, there was a decrease in serum NGF level versus control. A similar trend was characteristic of both MHO and MUHO. However, MUHO patients had a higher NGF level than MHO patients. The literature indicates that obesity is associated with an increase in the plasma concentration of NGF. It can be assumed that in obesity, there is a violation of NGF storage in platelets, which accelerates neurotrophin degradation. We found that BDNF concentration correlated with irisin levels in MUHO patients. Healthy donors had a weak association between NGF and VEGF levels. No such association was found in obese patients, but there was an association between NGF and leptin concentrations. In MHO, the concentration of NHF correlated with the content of leptin, irisin, osteocrin, insulin, and the HOMA-IR index. But in MUHO patients, we found only the relationship between NGF and adipokines (leptin, asprosin). It can be assumed that in patients with MHO, the replenishment of serum NGF occurs under the influence of muscle and adipose tissue. In the MUHO patients only the effect of adipose tissue on NGF was observed. Conclusion. Obesity, regardless of metabolic type, is associated with a decrease in serum NGF concentration. We showed that muscle and adipose tissues make a significant contribution to the serum NGF pool in the MHO patients. In MUHO there is no effect of muscle on the NGF level, but the effect of adipose tissue remains.

Keywords: neurotrophins, nerve growth factor, NGF, brain-derived neurotrophic factor, BDNF, obesity, metabolically healthy obesity, metabolically unhealthy obesity

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32 Solution Thermodynamics, Photophysical and Computational Studies of TACH2OX, a C-3 Symmetric 8-Hydroxyquinoline: Abiotic Siderophore Analogue of Enterobactin

Authors: B. K. Kanungo, Monika Thakur, Minati Baral

Abstract:

8-hydroxyquinoline, (8HQ), experiences a renaissance due to its utility as a building block in metallosupramolecular chemistry and its versatile use of its derivatives in various fields of analytical chemistry, materials science, and pharmaceutics. It forms stable complexes with a variety of metal ions. Assembly of more than one such unit to form a polydentate chelator enhances its coordinating ability and the related properties due to the chelate effect resulting in high stability constant. Keeping in view the above, a nonadentate chelator N-[3,5-bis(8-hydroxyquinoline-2-amido)cyclohexyl]-8-hydroxyquinoline-2-carboxamide, (TACH2OX), containing a central cis,cis-1,3,5-triaminocyclohexane appended to three 8-hydroxyquinoline at 2-position through amide linkage is developed, and its solution thermodynamics, photophysical and Density Functional Theory (DFT) studies were undertaken. The synthesis of TACH2OX was carried out by condensation of cis,cis-1,3,5-triaminocyclohexane, (TACH) with 8‐hydroxyquinoline‐2‐carboxylic acid. The brown colored solid has been fully characterized through melting point, infrared, nuclear magnetic resonance, electrospray ionization mass and electronic spectroscopy. In solution, TACH2OX forms protonated complexes below pH 3.4, which consecutively deprotonates to generate trinegative ion with the rise of pH. Nine protonation constants for the ligand were obtained that ranges between 2.26 to 7.28. The interaction of the chelator with two trivalent metal ion Fe3+ and Al3+ were studied in aqueous solution at 298 K. The metal-ligand formation constants (ML) obtained by potentiometric and spectrophotometric method agree with each other. The protonated and hydrolyzed species were also detected in the system. The in-silico studies of the ligand, as well as the complexes including their protonated and deprotonated species assessed by density functional theory technique, gave an accurate correlation with each observed properties such as the protonation constants, stability constants, infra-red, nmr, electronic absorption and emission spectral bands. The nature of electronic and emission spectral bands in terms of number and type were ascertained from time-dependent density functional theory study and the natural transition orbitals (NTO). The global reactivity indices parameters were used for comparison of the reactivity of the ligand and the complex molecules. The natural bonding orbital (NBO) analysis could successfully describe the structure and bonding of the metal-ligand complexes specifying the percentage of contribution in atomic orbitals in the creation of molecular orbitals. The obtained high value of metal-ligand formation constants indicates that the newly synthesized chelator is a very powerful synthetic chelator. The minimum energy molecular modeling structure of the ligand suggests that the ligand, TACH2OX, in a tripodal fashion firmly coordinates to the metal ion as hexa-coordinated chelate displaying distorted octahedral geometry by binding through three sets of N, O- donor atoms, present in each pendant arm of the central tris-cyclohexaneamine tripod.

Keywords: complexes, DFT, formation constant, TACH2OX

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31 Assessment of Physical Activity and Sun Exposure of Saudi Patients with Type 2 Diabetes Mellitus in Ramadan and Non-Ramadan Periods

Authors: Abdullah S. Alghamdi, Khaled Alghamdi, Richard O. Jenkins, Parvez I. Haris

Abstract:

Background: Physical activity is an important factor in the treatment and prevention of type 2 diabetes mellitus (T2DM). Reduction in HbA1c level, an important diabetes biomarker, was reported in patients who increased their daily physical activity. Although the ambient temperature was reported to be positively correlated to a negative impact on health and increase the incidences of diabetes, the exposure to bright sunlight was recently found to be associated with enhanced insulin sensitivity and improved beta-cell function. How Ramadan alters physical activity, and especially sunlight exposure, has not been adequately investigated. Aim: This study aimed to assess the physical activity and sun exposure of Saudis with T2DM over different periods (before, during, and after Ramadan) and related this to HbA1c levels. Methods: This study recruited 82 Saudis with T2DM, who chose to fast during Ramadan, from the Endocrine and Diabetic Centre of Al Iman General Hospital, Riyadh, Saudi Arabia. Ethical approvals for this study were obtained from De Montfort University and Saudi Ministry of Health. Physical activity and sun exposure were assessed by a self-administered questionnaire. Physical activity was estimated using the International Physical Activity Questionnaire (IPAQ), while the sun exposure was assessed by asking the patients about their hours per week of direct exposure to the sun, and daily hours spent outdoors. Blood samples were collected in each period for measuring HbA1c. Results: Low physical activity was observed in more than 60% of the patients, with no significant changes between periods. There were no significant variances between periods in the daily hours spent outdoors and the total number of weekly hours of direct exposure to the sun. The majority of patients reported only few hours of exposure to the sun (1h or less per week) and time spent outdoors (1h or less per day). The mean HbA1c significantly changed between periods (P = 0.001), with lowest level during Ramadan. There were significant differences in the mean HbA1c between the groups for the level of physical activity (P < 0.001), with significant lower mean HbA1c in the higher-level group. There were no significant variances in the mean of HbA1c between the groups for the daily hours spent outdoors. The mean HbA1c of the patients, who reported never in their total weekly hours of exposure to the sun, was significantly lower than the mean HbA1c of those who reported 1 hour or less (P = 0.001). Conclusion: Physical inactivity was prevalent among the study population with very little exposure to the sun or time spent outdoors. Higher level of physical activity was associated with lower mean HbA1c levels. Encouraging T2DM patients to achieve the recommended levels of physical activity may help them to obtain greater benefits of Ramadan fasting, such as reducing their HbA1c levels. The impact of low direct exposure to the sun and the time spent outdoors needs to be further investigated in both healthy and diabetic patients.

Keywords: diabetes, fasting, physical activity, sunlight, Ramadan

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30 Evaluation of Antidiabetic Activity of a Combination Extract of Nigella Sativa & Cinnamomum Cassia in Streptozotocin Induced Type-I Diabetic Rats

Authors: Ginpreet Kaur, Mohammad Yasir Usmani, Mohammed Kamil Khan

Abstract:

Diabetes mellitus is a disease with a high global burden and results in significant morbidity and mortality. In India, the number of people suffering with diabetes is expected to rise from 19 to 57 million in 2025. At present, interest in herbal remedies is growing to reduce the side effects associated with conventional dosage form like oral hypoglycemic agents and insulin for the treatment of diabetes mellitus. Our aim was to investigate the antidiabetic activities of combinatorial extract of N. sativa & C. cassia in Streptozotocin induced type-I Diabetic Rats. Thus, the present study was undertaken to screen postprandial glucose excursion potential through α- glucosidase inhibitory activity (In Vitro) and effect of combinatorial extract of N. sativa & C. cassia in Streptozotocin induced type-I Diabetic Rats (In Vivo). In addition changes in body weight, plasma glucose, lipid profile and kidney profile were also determined. The IC50 values for both extract and Acarbose was calculated by extrapolation method. Combinatorial extract of N. sativa & C. cassia at different dosages (100 and 200 mg/kg orally) and Metformin (50 mg/kg orally) as the standard drug was administered for 28 days and then biochemical estimation, body weights and OGTT (Oral glucose tolerance test) were determined. Histopathological studies were also performed on kidney and pancreatic tissue. In In-Vitro the combinatorial extract shows much more inhibiting effect than the individual extracts. The results reveals that combinatorial extract of N. sativa & C. cassia has shown significant decrease in plasma glucose (p<0.0001), total cholesterol and LDL levels when compared with the STZ group The decreasing level of BUN and creatinine revealed the protection of N. sativa & C. cassia extracts against nephropathy associated with diabetes. Combination of N. sativa & C. cassia significantly improved glucose tolerance to exogenously administered glucose (2 g/kg) after 60, 90 and 120 min interval on OGTT in high dose streptozotocin induced diabetic rats compared with the untreated control group. Histopathological studies shown that treatment with N. sativa & C. cassia extract alone and in combination restored pancreatic tissue integrity and was able to regenerate the STZ damaged pancreatic β cells. Thus, the present study reveals that combination of N. sativa & C. cassia extract has significant α- glucosidase inhibitory activity and thus has great potential as a new source for diabetes treatment.

Keywords: lipid levels, OGTT, diabetes, herbs, glucosidase

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29 Blood Microbiome in Different Metabolic Types of Obesity

Authors: Irina M. Kolesnikova, Andrey M. Gaponov, Sergey A. Roumiantsev, Tatiana V. Grigoryeva, Dilyara R. Khusnutdinova, Dilyara R. Kamaldinova, Alexander V. Shestopalov

Abstract:

Background. Obese patients have unequal risks of metabolic disorders. It is accepted to distinguish between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). MUHO patients have a high risk of metabolic disorders, insulin resistance, and diabetes mellitus. Among the other things, the gut microbiota also contributes to the development of metabolic disorders in obesity. Obesity is accompanied by significant changes in the gut microbial community. In turn, bacterial translocation from the intestine is the basis for the blood microbiome formation. The aim was to study the features of the blood microbiome in patients with various metabolic types of obesity. Patients, materials, methods. The study included 116 healthy donors and 101 obese patients. Depending on the metabolic type of obesity, the obese patients were divided into subgroups with MHO (n=36) and MUHO (n=53). Quantitative and qualitative assessment of the blood microbiome was based on metagenomic analysis. Blood samples were used to isolate DNA and perform sequencing of the variable v3-v4 region of the 16S rRNA gene. Alpha diversity indices (Simpson index, Shannon index, Chao1 index, phylogenetic diversity, the number of observed operational taxonomic units) were calculated. Moreover, we compared taxa (phyla, classes, orders, and families) in terms of isolation frequency and the taxon share in the total bacterial DNA pool between different patient groups. Results. In patients with MHO, the characteristics of the alpha-diversity of the blood microbiome were like those of healthy donors. However, MUHO was associated with an increase in all diversity indices. The main phyla of the blood microbiome were Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. Cyanobacteria, TM7, Thermi, Verrucomicrobia, Chloroflexi, Acidobacteria, Planctomycetes, Gemmatimonadetes, and Tenericutes were found to be less significant phyla of the blood microbiome. Phyla Acidobacteria, TM7, and Verrucomicrobia were more often isolated in blood samples of patients with MUHO compared with healthy donors. Obese patients had a decrease in some taxonomic ranks (Bacilli, Caulobacteraceae, Barnesiellaceae, Rikenellaceae, Williamsiaceae). These changes appear to be related to the increased diversity of the blood microbiome observed in obesity. An increase of Lachnospiraceae, Succinivibrionaceae, Prevotellaceae, and S24-7 was noted for MUHO patients, which, apparently, is explained by a magnification in intestinal permeability. Conclusion. Blood microbiome differs in obese patients and healthy donors at class, order, and family levels. Moreover, the nature of the changes is determined by the metabolic type of obesity. MUHO linked to increased diversity of the blood microbiome. This appears to be due to increased microbial translocation from the intestine and non-intestinal sources.

Keywords: blood microbiome, blood bacterial DNA, obesity, metabolically healthy obesity, metabolically unhealthy obesity

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28 Preliminary Study Investigating Trunk Muscle Fatigue and Cognitive Function in Event Riders during a Simulated Jumping Test

Authors: Alice Carter, Lucy Dumbell, Lorna Cameron, Victoria Lewis

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The Olympic discipline of eventing is the triathlon of equestrian sport, consisting of dressage, cross-country and show jumping. Falls on the cross-country are common and can be serious even causing death to rider. Research identifies an increased risk of a fall with an increasing number of obstacles and for jumping efforts later in the course suggesting fatigue maybe a contributing factor. Advice based on anecdotal evidence suggests riders undertake strength and conditioning programs to improve their ‘core’, thus improving their ability to maintain and control their riding position. There is little empirical evidence to support this advice. Therefore, the aim of this study is to investigate truck muscle fatigue and cognitive function during a simulated jumping test. Eight adult riders participated in a riding test on a Racewood Event simulator for 10 minutes, over a continuous jumping programme. The SEMG activity of six trunk muscles were bilaterally measured at every minute, and normalised root mean squares (RMS) and median frequencies (MDF) were computed from the EMG power spectra. Visual analogue scales (VAS) measuring Fatigue and Pain levels and Cognitive Function ‘tapping’ tests were performed before and after the riding test. Average MDF values for all muscles differed significantly between each sampled minute (p = 0.017), however a consistent decrease from Minute 1 and Minute 9 was not found, suggesting the trunk muscles fatigued and then recovered as other muscle groups important in maintaining the riding position during dynamic movement compensated. Differences between the MDF and RMS of different muscles were highly significant (H=213.01, DF=5, p < 0.001), supporting previous anecdotal evidence that different trunk muscles carry out different roles of posture maintenance during riding. RMS values were not significantly different between the sampled minutes or between riders, suggesting the riding test produced a consistent and repeatable effect on the trunk muscles. MDF values differed significantly between riders (H=50.8, DF = 5, p < 0.001), suggesting individuals may experience localised muscular fatigue of the same test differently, and that other parameters of physical fitness should be investigated to provide conclusions. Lumbar muscles were shown to be important in maintaining the position, therefore physical training program should focus on these areas. No significant differences were found between pre- and post-riding test VAS Pain and Fatigue scores or cognitive function test scores, suggesting the riding test was not significantly fatiguing for participants. However, a near significant correlation was found between time of riding test and VAS Pain score (p = 0.06), suggesting somatic pain may be a limiting factor to performance. No other correlations were found between the factors of participant riding test time, VAS Pain and Fatigue, however a larger sample needs to be tested to improve statistical analysis. The findings suggest the simulator riding test was not sufficient to provoke fatigue in the riders, however foundations for future studies have been laid to enable methodologies in realistic eventing settings.

Keywords: eventing, fatigue, horse-rider, surface EMG, trunk muscles

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27 Effect of Natural and Urban Environments on the Perception of Thermal Pain – Experimental Research Using Virtual Environments

Authors: Anna Mucha, Ewa Wojtyna, Anita Pollak

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The environment in which an individual resides and observes may play a meaningful role in well-being and related constructs. Contact with nature may have a positive influence of natural environments on individuals, impacting mood and psychophysical sensations, such as pain relief. Conversely, urban settings, dominated by concrete elements, might lead to mood decline and heightened stress levels. Similarly, the situation may appear in the case of the perception of virtual environments. However, this is a topic that requires further exploration, especially in the context of relationships with pain. The aforementioned matters served as the basis for formulating and executing the outlined experimental research within the realm of environmental psychology, leveraging new technologies, notably virtual reality (VR), which is progressively gaining prominence in the domain of mental health. The primary objective was to investigate the impact of a simulated virtual environment, mirroring a natural setting abundant in greenery, on the perception of acute pain induced by thermal stimuli (high temperature) – encompassing intensity, unpleasantness, and pain tolerance. Comparative analyses were conducted between the virtual natural environment (intentionally constructed in the likeness of a therapeutic garden), virtual urban environment, and a control group devoid of virtual projections. Secondary objectives aimed to determine the mutual relationships among variables such as positive and negative emotions, preferences regarding virtual environments, sense of presence, and restorative experience in the context of the perception of presented virtual environments and induced thermal pain. The study encompassed 126 physically healthy Polish adults, distributing 42 individuals across each of the three comparative groups. Oculus Rift VR technology and the TSA-II neurosensory analyzer facilitated the experiment. Alongside demographic data, participants' subjective feelings concerning virtual reality and pain were evaluated using the Visual Analogue Scale (VAS), the original Restorative Experience in the Virtual World questionnaire (Doświadczenie Regeneracji w Wirtualnym Świecie), and an adapted Slater-Usoh-Steed (SUS) questionnaire. Results of statistical and psychometric analyses, such as Kruskal-Wallis tests, Wilcoxon tests, and contrast analyses, underscored the positive impact of the virtual natural environment on individual pain perception and mood. The virtual natural environment outperformed the virtual urban environment and the control group without virtual projection, particularly in subjective pain components like intensity and unpleasantness. Variables such as restorative experience, sense of presence and virtual environment preference also proved pivotal in pain perception and pain tolerance threshold alterations, contingent on specific conditions. This implies considerable application potential for virtual natural environments across diverse realms of psychology and related fields, among others as a supportive analgesic approach and a form of relaxation following psychotherapeutic sessions.

Keywords: environmental psychology, nature, acute pain, emotions, vitrual reality, virtual environments

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26 Mirna Expression Profile is Different in Human Amniotic Mesenchymal Stem Cells Isolated from Obese Respect to Normal Weight Women

Authors: Carmela Nardelli, Laura Iaffaldano, Valentina Capobianco, Antonietta Tafuto, Maddalena Ferrigno, Angela Capone, Giuseppe Maria Maruotti, Maddalena Raia, Rosa Di Noto, Luigi Del Vecchio, Pasquale Martinelli, Lucio Pastore, Lucia Sacchetti

Abstract:

Maternal obesity and nutrient excess in utero increase the risk of future metabolic diseases in the adult life. The mechanisms underlying this process are probably based on genetic, epigenetic alterations and changes in foetal nutrient supply. In mammals, the placenta is the main interface between foetus and mother, it regulates intrauterine development, modulates adaptive responses to sub optimal in uterus conditions and it is also an important source of human amniotic mesenchymal stem cells (hA-MSCs). We previously highlighted a specific microRNA (miRNA) profiling in amnion from obese (Ob) pregnant women, here we compared the miRNA expression profile of hA-MSCs isolated from (Ob) and control (Co) women, aimed to search for any alterations in metabolic pathways that could predispose the new-born to the obese phenotype. Methods: We isolated, at delivery, hA-MSCs from amnion of 16 Ob- and 7 Co-women with pre-pregnancy body mass index (mean/SEM) 40.3/1.8 and 22.4/1.0 kg/m2, respectively. hA-MSCs were phenotyped by flow cytometry. Globally, 384 miRNAs were evaluated by the TaqMan Array Human MicroRNA Panel v 1.0 (Applied Biosystems). By the TargetScan program we selected the target genes of the miRNAs differently expressed in Ob- vs Co-hA-MSCs; further, by KEGG database, we selected the statistical significant biological pathways. Results: The immunophenotype characterization confirmed the mesenchymal origin of the isolated hA-MSCs. A large percentage of the tested miRNAs, about 61.4% (232/378), was expressed in hA-MSCs, whereas 38.6% (146/378) was not. Most of the expressed miRNAs (89.2%, 207/232) did not differ between Ob- and Co-hA-MSCs and were not further investigated. Conversely, 4.8% of miRNAs (11/232) was higher and 6.0% (14/232) was lower in Ob- vs Co-hA-MSCs. Interestingly, 7/232 miRNAs were obesity-specific, being expressed only in hA-MSCs isolated from obese women. Bioinformatics showed that these miRNAs significantly regulated (P<0.001) genes belonging to several metabolic pathways, i.e. MAPK signalling, actin cytoskeleton, focal adhesion, axon guidance, insulin signaling, etc. Conclusions: Our preliminary data highlight an altered miRNA profile in Ob- vs Co-hA-MSCs and suggest that an epigenetic miRNA-based mechanism of gene regulation could affect pathways involved in placental growth and function, thereby potentially increasing the newborn’s risk of metabolic diseases in the adult life.

Keywords: hA-MSCs, obesity, miRNA, biosystem

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25 Impact of Helicobacter pylori Infection on Colorectal Adenoma-Colorectal Carcinoma Sequence

Authors: Jannis Kountouras, Nikolaos Kapetanakis, Stergios A. Polyzos, Apostolis Papaeftymiou, Panagiotis Katsinelos, Ioannis Venizelos, Christina Nikolaidou, Christos Zavos, Iordanis Romiopoulos, Elena Tsiaousi, Evangelos Kazakos, Michael Doulberis

Abstract:

Background & Aims: Helicobacter pylori infection (Hp-I) has been recognized as a substantial risk agent involved in gastrointestinal (GI) tract oncogenesis by stimulating cancer stem cells (CSCs), oncogenes, immune surveillance processes, and triggering GI microbiota dysbiosis. We aimed to investigate the possible involvement of active Hp-I in the sequence: chronic inflammation–adenoma–colorectal cancer (CRC) development. Methods: Four pillars were investigated: (i) endoscopic and conventional histological examinations of patients with CRC, colorectal adenomas (CRA) versus controls to detect the presence of active Hp-I; (ii) immunohistochemical determination of the presence of Hp; expression of CD44, an indicator of CSCs and/or bone marrow-derived stem cells (BMDSCs); expressions of oncogene Ki67 and anti-apoptotic Bcl-2 protein; (iii) expression of CD45, indicator of immune surveillance locally (assessing mainly T and B lymphocytes locally); and (iv) correlation of the studied parameters with the presence or absence of Hp-I. Results: Among 50 patients with CRC, 25 with CRA, and 10 controls, a significantly higher presence of Hp-I in the CRA (68%) and CRC group (84%) were found compared with controls (30%). The presence of Hp-I with accompanying immunohistochemical expression of CD44 in biopsy specimens was revealed in a high proportion of patients with CRA associated with moderate/severe dysplasia (88%) and CRC patients with moderate/severe degree of malignancy (91%). Comparable results were also obtained for Ki67, Bcl-2, and CD45 immunohistochemical expressions. Concluding Remarks: Hp-I seems to be involved in the sequence: CRA – dysplasia – CRC, similarly to the upper GI tract oncogenesis, by several pathways such as the following: Beyond Hp-I associated insulin resistance, the major underlying mechanism responsible for the metabolic syndrome (MetS) that increase the risk of colorectal neoplasms, as implied by other Hp-I related MetS pathologies, such as non-alcoholic fatty liver disease and upper GI cancer, the disturbance of the normal GI microbiota (i.e., dysbiosis) and the formation of an irritative biofilm could contribute to a perpetual inflammatory upper GIT and colon mucosal damage, stimulating CSCs or recruiting BMDSCs and affecting oncogenes and immune surveillance processes. Further large-scale relative studies with a pathophysiological perspective are necessary to demonstrate in-depth this relationship.

Keywords: Helicobacter pylori, colorectal cancer, colorectal adenomas, gastrointestinal oncogenesis

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24 Digital Transformation in Fashion System Design: Tools and Opportunities

Authors: Margherita Tufarelli, Leonardo Giliberti, Elena Pucci

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The fashion industry's interest in virtuality is linked, on the one hand, to the emotional and immersive possibilities of digital resources and the resulting languages and, on the other, to the greater efficiency that can be achieved throughout the value chain. The interaction between digital innovation and deep-rooted manufacturing traditions today translates into a paradigm shift for the entire fashion industry where, for example, the traditional values of industrial secrecy and know-how give way to experimentation in an open as well as participatory way, and the complete emancipation of virtual reality from actual 'reality'. The contribution aims to investigate the theme of digitisation in the Italian fashion industry, analysing its opportunities and the criticalities that have hindered its diffusion. There are two reasons why the most common approach in the fashion sector is still analogue: (i) the fashion product lives in close contact with the human body, so the sensory perception of materials plays a central role in both the use and the design of the product, but current technology is not able to restore the sense of touch; (ii) volumes are obtained by stitching flat surfaces that once assembled, given the flexibility of the material, can assume almost infinite configurations. Managing the fit and styling of virtual garments involves a wide range of factors, including mechanical simulation, collision detection, and user interface techniques for garment creation. After briefly reviewing some of the salient historical milestones in the resolution of problems related to the digital simulation of deformable materials and the user interface for the procedures for the realisation of the clothing system, the paper will describe the operation and possibilities offered today by the latest generation of specialised software. Parametric avatars and digital sartorial approach; drawing tools optimised for pattern making; materials both from the point of view of simulated physical behaviour and of aesthetic performance, tools for checking wearability, renderings, but also tools and procedures useful to companies both for dialogue with prototyping software and machinery and for managing the archive and the variants to be made. The article demonstrates how developments in technology and digital procedures now make it possible to intervene in different stages of design in the fashion industry. An integrated and additive process in which the constructed 3D models are usable both in the prototyping and communication of physical products and in the possible exclusively digital uses of 3D models in the new generation of virtual spaces. Mastering such tools requires the acquisition of specific digital skills and, at the same time, traditional skills for the design of the clothing system, but the benefits are manifold and applicable to different business dimensions. We are only at the beginning of the global digital transformation: the emergence of new professional figures and design dynamics leaves room for imagination, but in addition to applying digital tools to traditional procedures, traditional fashion know-how needs to be transferred into emerging digital practices to ensure the continuity of the technical-cultural heritage beyond the transformation.

Keywords: digital fashion, digital technology and couture, digital fashion communication, 3D garment simulation

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23 Buoyant Gas Dispersion in a Small Fuel Cell Enclosure: A Comparison Study Using Plain and Pressed Louvre Vent Passive Ventilation Schemes

Authors: T. Ghatauray, J. Ingram, P. Holborn

Abstract:

The transition from a ‘carbon rich’ fossil fuel dependent to a ‘sustainable’ and ‘renewable’ hydrogen based society will see the deployment of hydrogen fuel cells (HFC) in transport applications and in the generation of heat and power for buildings, as part of a decentralised power network. Many deployments will be low power HFCs for domestic combined heat and power (CHP) and commercial ‘transportable’ HFCs for environmental situations, such as lighting and telephone towers. For broad commercialisation of small fuel cells to be achieved there needs to be significant confidence in their safety in both domestic and environmental applications. Low power HFCs are housed in protective steel enclosures. Standard enclosures have plain rectangular ventilation openings intended for thermal management of electronics and not the dispersion of a buoyant gas. Degradation of the HFC or supply pipework in use could lead to a low-level leak and a build-up of hydrogen gas in the enclosure. Hydrogen’s wide flammable range (4-75%) is a significant safety concern, with ineffective enclosure ventilation having the potential to cause flammable mixtures to develop with the risk of explosion. Mechanical ventilation is effective at managing enclosure hydrogen concentrations, but drains HFC power and is vulnerable to failure. This is undesirable in low power and remote installations and reliable passive ventilation systems are preferred. Passive ventilation depends upon buoyancy driven flow, with the size, shape and position of ventilation openings critical for producing predictable flows and maintaining low buoyant gas concentrations. With environmentally sited enclosures, ventilation openings with pressed horizontal and angled louvres are preferred to protect the HFC and electronics inside. There is an economic cost to adding louvres, but also a safety concern. A question arises over whether the use of pressed louvre vents impairs enclosure passive ventilation performance, when compared to same opening area plain vents. Comparison small enclosure (0.144m³) tests of same opening area pressed louvre and plain vents were undertaken. A displacement ventilation arrangement was incorporated into the enclosure with opposing upper and lower ventilation openings. A range of vent areas were tested. Helium (used as a safe analogue for hydrogen) was released from a 4mm nozzle at the base of the enclosure to simulate a hydrogen leak at leak rates from 1 to 10 lpm. Helium sensors were used to record concentrations at eight heights in the enclosure. The enclosure was otherwise empty. These tests determined that the use of pressed and angled louvre ventilation openings on the enclosure impaired the passive ventilation flow and increased helium concentrations in the enclosure. High-level stratified buoyant gas layers were also found to be deeper than with plain vent openings and were within the flammable range. The presence of gas within the flammable range is of concern, particularly as the addition of the fuel cell and electronics in the enclosure would further reduce the available volume and increase concentrations. The opening area of louvre vents would need to be greater than equivalent plain vents to achieve comparable ventilation flows or alternative schemes would need to be considered.

Keywords: enclosure, fuel cell, helium, hydrogen safety, louvre vent, passive ventilation

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22 Cobalamin, Folate and Metabolic Syndrome Parameters in Pediatric Morbid Obesity and Metabolic Syndrome

Authors: Mustafa M. Donma, Orkide Donma

Abstract:

Obesity is known to be associated with many clinically important diseases including metabolic syndrome (MetS). Vitamin B12 plays essential roles in fat and protein metabolisms and its cooperation with vitamin B9 is well-known. The aim of this study is to investigate the possible contributions as well as associations of these micronutrients upon obesity and MetS during childhood. A total of 128 children admitted to Namik Kemal University, Medical Faculty, Department of Pediatrics Outpatient Clinics were included into the scope of this study. The mean age±SEM of 92 morbid obese (MO) children and 36 with MetS were 118.3±3.8 months and 129.5±6.4 months, respectively (p > 0.05). The study was approved by Namık Kemal University, Medical Faculty Ethics Committee. Written informed consent forms were obtained from the parents. Demographic features and anthropometric measurements were recorded. WHO BMI-for age percentiles were used. The values above 99 percentile were defined as MO. Components of MetS [waist circumference (WC), fasting blood glucose (FBG), triacylglycerol (TRG), high density lipoprotein cholesterol (HDL-Chol), systolic pressure (SP), diastolic pressure (DP)] were determined. Routine laboratory tests were performed. Serum vitamin B12 concentrations were measured using electrochemiluminescence immunoassay. Vitamin B9 was analyzed by an immunoassay analyzer. Values for vitamin B12 < 148 pmol/L, 148-221 pmol/L, > 221 pmol/L were accepted as low, borderline and normal, respectively. Vitamin B9 levels ≤ 4 mcg/L defined deficiency state. Statistical evaluations were performed by SPSSx Version 16.0. p≤0.05 was accepted as statistical significance level. Statistically higher body mass index (BMI), WC, hip circumference (C) and neck C were calculated in MetS group compared to children with MO. No difference was noted for head C. All MetS components differed between the groups (SP, DP p < 0.001; WC, FBG, TRG p < 0.01; HDL-Chol p < 0.05). Significantly decreased vitamin B9 and vitamin B12 levels were detected (p < 0.05) in children with MetS. In both groups percentage of folate deficiency was 5.5%. No cases were below < 148 pmol/L. However, in MO group 14.3% and in MetS group 22.2% of the cases were of borderline status. In MO group B12 levels were negatively correlated with BMI, WC, hip C and head C, but not with neck C. WC, hip C, head C and neck C were all negatively correlated with HDL-Chol. None of these correlations were observed in the group of children with MetS. Strong positive correlation between FBG and insulin as well as strong negative correlation between TRG and HDL-Chol detected in MO children were lost in MetS group. Deficiency state end-products of both B9 and B12 may interfere with the expected profiles of MetS components. In this study, the alterations in MetS components affected vitamin B12 metabolism and also its associations with anthropometric body measurements. Further increases in vitamin B12 and vitamin B9 deficiency in MetS associated with the increased vitamin B12 as well as vitamin B9 deficiency metabolites may add to MetS parameters.

Keywords: children, cobalamin, folate, metabolic syndrome, obesity

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21 Hypoglossal Nerve Stimulation (Baseline vs. 12 months) for Obstructive Sleep Apnea: A Meta-Analysis

Authors: Yasmeen Jamal Alabdallat, Almutazballlah Bassam Qablan, Hamza Al-Salhi, Salameh Alarood, Ibraheem Alkhawaldeh, Obada Abunar, Adam Abdallah

Abstract:

Obstructive sleep apnea (OSA) is a disorder caused by the repeated collapse of the upper airway during sleep. It is the most common cause of sleep-related breathing disorder, as OSA can cause loud snoring, daytime fatigue, or more severe problems such as high blood pressure, cardiovascular disease, coronary artery disease, insulin-resistant diabetes, and depression. The hypoglossal nerve stimulator (HNS) is an implantable medical device that reduces the occurrence of obstructive sleep apnea by electrically stimulating the hypoglossal nerve in rhythm with the patient's breathing, causing the tongue to move. This stimulation helps keep the patient's airways clear while they sleep. This systematic review and meta-analysis aimed to assess the clinical outcome of hypoglossal nerve stimulation as a treatment of obstructive sleep apnea. A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials was conducted from inception until August 2022. Studies assessing the following clinical outcomes (Apnea-Hypopnea Index (AHI), Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Oxygen Desaturation Indices (ODI), (Oxygen Saturation (SaO2)) were pooled in the meta-analysis using Review Manager Software. We assessed the quality of studies according to the Cochrane risk-of-bias tool for randomized trials (RoB2), Risk of Bias In Non-randomized Studies - of Interventions (ROBINS-I), and a modified version of NOS for the non-comparative cohort studies.13 Studies (Six Clinical Trials and Seven prospective cohort studies) with a total of 817 patients were included in the meta-analysis. The results of AHI were reported in 11 studies examining OSA 696 patients. We found that there was a significant improvement in the AHI after 12 months of HNS (MD = 18.2 with 95% CI, (16.7 to 19.7; I2 = 0%); P < 0.00001). Further, 12 studies reported the results of ESS after 12 months of intervention with a significant improvement in the range of sleepiness among the examined 757 OSA patients (MD = 5.3 with 95% CI, (4.75 to 5.86; I2 = 65%); P < 0.0001). Moreover, nine studies involving 699 participants reported the results of FOSQ after 12 months of HNS with a significant reported improvement (MD = -3.09 with 95% CI, (-3.41 to 2.77; I2 = 0%); P < 0.00001). In addition, ten studies reported the results of ODI with a significant improvement after 12 months of HNS among the 817 examined patients (MD = 14.8 with 95% CI, (13.25 to 16.32; I2 = 0%); P < 000001). The Hypoglossal Nerve Stimulation showed a significant positive impact on obstructive sleep apnea patients after 12 months of therapy in terms of apnea-hypopnea index, oxygen desaturation indices, manifestations of the behavioral morbidity associated with obstructive sleep apnea, and functional status resulting from sleepiness.

Keywords: apnea, meta-analysis, hypoglossal, stimulation

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20 Fungal Cellulase/Xylanase Complex and Their Industrial Applications

Authors: L. Kutateldze, T. Urushadze, R. Khvedelidze, N. Zakariashvili, I. Khokhashvili, T. Sadunishvili

Abstract:

Microbial cellulase/xylanase have shown their potential application in various industries including pulp and paper, textile, laundry, biofuel production, food and feed industry, brewing, and agriculture. Extremophilic micromycetes and their enzymes that are resistant to critical values of temperature and pH, and retaining enzyme activity for a long time are of great industrial interest. Among strains of microscopic fungi from the collection of S. Durmishidze Institute of Biochemistry and Biotechnology, strains isolated from different ecological niches of Southern Caucasus-active producers of cellulase/xylanase have been selected by means of screening under deep cultivation conditions. Extremophilic micromycetes and their enzymes that are resistant to critical values of temperature and pH, and retaining enzyme activity for a long time are of great industrial interest. Among strains of microscopic fungi from the collection of S. Durmishidze Institute of Biochemistry and Biotechnology, strains isolated from different ecological niches of Southern Caucasus-active producers of cellulase/xylanase have been selected by means of screening under deep cultivation conditions. Representatives of the genera Aspergillus, Penicillium and Trichoderma are outstanding by relatively high activities of these enzymes. Among the producers were revealed thermophilic strains, representatives of the genus Aspergillus-Aspergillus terreus, Aspergillus versicolor, Aspergillus wentii, also strains of Sporotrichum pulverulentum and Chaetomium thermophile. As a result of optimization of cultivation media and conditions, activities of enzymes produced by the strains have been increased by 4 -189 %. Two strains, active producers of cellulase/xylanase – Penicillium canescence E2 (mesophile) and Aspergillus versicolor Z17 (thermophile) were chosen for further studies. Cellulase/xylanase enzyme preparations from two different genera of microscopic fungi Penicillium canescence E2 and Aspergillus versicolor Z 17 were obtained with activities 220 U/g /1200 U/g and 125 U/g /940 U/g, correspondingly. Main technical characteristics were as follows: the highest enzyme activities were obtained for mesophilic strain Penicillium canescence E2 at 45-500C, while almost the same enzyme activities were fixed for the thermophilic strain Aspergillus versicolor Z 17 at temperature 60-65°C, exceeding the temperature optimum of the mesophile by 150C. Optimum pH of action of the studied cellulase/xylanases from mesophileic and thermophilic strains were similar and equaled to 4.5-5.0 It has been shown that cellulase/xylanase technical preparations from selected strains of Penicillium canescence E2 and Aspergillus versicolor Z17 hydrolyzed cellulose of untreated wheat straw to reducible sugars by 46-52%, and to glucose by 22-27%. However the thermophilic enzyme preparations from the thermophilic A.versicolor strains conducted the process at 600C higher by 100C as compared to mesophlic analogue. Rate of hydrolyses of the pretreated substrate by the same enzyme preparations to reducible sugars and glucose conducted at optimum for their action 60 and 500C was 52-61% and 29-33%, correspondingly. Thus, maximum yield of glucose and reducible sugars form untreated and pretreated wheat straw was achieved at higher temperature (600C) by enzyme preparations from thermophilic strain, which gives advantage for their industrial application.

Keywords: cellulase/xylanase, cellulose hydrolysis, microscopic fungi, thermophilic strain

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19 Leveraging the HDAC Inhibitory Pharmacophore to Construct Deoxyvasicinone Based Tractable Anti-Lung Cancer Agent and pH-Responsive Nanocarrier

Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali

Abstract:

A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

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18 Improved Morphology in Sequential Deposition of the Inverted Type Planar Heterojunction Solar Cells Using Cheap Additive (DI-H₂O)

Authors: Asmat Nawaz, Ceylan Zafer, Ali K. Erdinc, Kaiying Wang, M. Nadeem Akram

Abstract:

Hybrid halide Perovskites with the general formula ABX₃, where X = Cl, Br or I, are considered as an ideal candidates for the preparation of photovoltaic devices. The most commonly and successfully used hybrid halide perovskite for photovoltaic applications is CH₃NH₃PbI₃ and its analogue prepared from lead chloride, commonly symbolized as CH₃NH₃PbI₃_ₓClₓ. Some researcher groups are using lead free (Sn replaces Pb) and mixed halide perovskites for the fabrication of the devices. Both mesoporous and planar structures have been developed. By Comparing mesoporous structure in which the perovskite materials infiltrate into mesoporous metal oxide scaffold, the planar architecture is much simpler and easy for device fabrication. In a typical perovskite solar cell, a perovskite absorber layer is sandwiched between the hole and electron transport. Upon the irradiation, carriers are created in the absorber layer that can travel through hole and electron transport layers and the interface in between. We fabricated inverted planar heterojunction structure ITO/PEDOT/ Perovskite/PCBM/Al, based solar cell via two-step spin coating method. This is also called Sequential deposition method. A small amount of cheap additive H₂O was added into PbI₂/DMF to make a homogeneous solution. We prepared four different solution such as (W/O H₂O, 1% H₂O, 2% H₂O, 3% H₂O). After preparing, the whole night stirring at 60℃ is essential for the homogenous precursor solutions. We observed that the solution with 1% H₂O was much more homogenous at room temperature as compared to others. The solution with 3% H₂O was precipitated at once at room temperature. The four different films of PbI₂ were formed on PEDOT substrates by spin coating and after that immediately (before drying the PbI₂) the substrates were immersed in the methyl ammonium iodide solution (prepared in isopropanol) for the completion of the desired perovskite film. After getting desired films, rinse the substrates with isopropanol to remove the excess amount of methyl ammonium iodide and finally dried it on hot plate only for 1-2 minutes. In this study, we added H₂O in the PbI₂/DMF precursor solution. The concept of additive is widely used in the bulk- heterojunction solar cells to manipulate the surface morphology, leading to the enhancement of the photovoltaic performance. There are two most important parameters for the selection of additives. (a) Higher boiling point w.r.t host material (b) good interaction with the precursor materials. We observed that the morphology of the films was improved and we achieved a denser, uniform with less cavities and almost full surface coverage films but only using precursor solution having 1% H₂O. Therefore, we fabricated the complete perovskite solar cell by sequential deposition technique with precursor solution having 1% H₂O. We concluded that with the addition of additives in the precursor solutions one can easily be manipulate the morphology of the perovskite film. In the sequential deposition method, thickness of perovskite film is in µm and the charge diffusion length of PbI₂ is in nm. Therefore, by controlling the thickness using other deposition methods for the fabrication of solar cells, we can achieve the better efficiency.

Keywords: methylammonium lead iodide, perovskite solar cell, precursor composition, sequential deposition

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17 A Peg Board with Photo-Reflectors to Detect Peg Insertion and Pull-Out Moments

Authors: Hiroshi Kinoshita, Yasuto Nakanishi, Ryuhei Okuno, Toshio Higashi

Abstract:

Various kinds of pegboards have been developed and used widely in research and clinics of rehabilitation for evaluation and training of patient’s hand function. A common measure in these peg boards is a total time of performance execution assessed by a tester’s stopwatch. Introduction of electrical and automatic measurement technology to the apparatus, on the other hand, has been delayed. The present work introduces the development of a pegboard with an electric sensor to detect moments of individual peg’s insertion and removal. The work also gives fundamental data obtained from a group of healthy young individuals who performed peg transfer tasks using the pegboard developed. Through trails and errors in pilot tests, two 10-hole peg-board boxes installed with a small photo-reflector and a DC amplifier at the bottom of each hole were designed and built by the present authors. The amplified electric analogue signals from the 20 reflectors were automatically digitized at 500 Hz per channel, and stored in a PC. The boxes were set on a test table at different distances (25, 50, 75, and 125 mm) in parallel to examine the effect of hole-to-hole distance. Fifty healthy young volunteers (25 in each gender) as subjects of the study performed successive fast 80 time peg transfers at each distance using their dominant and non-dominant hands. The data gathered showed a clear-cut light interruption/continuation moment by the pegs, allowing accurately (no tester’s error involved) and precisely (an order of milliseconds) to determine the pull out and insertion times of each peg. This further permitted computation of individual peg movement duration (PMD: from peg-lift-off to insertion) apart from hand reaching duration (HRD: from peg insertion to lift-off). An accidental drop of a peg led to an exceptionally long ( < mean + 3 SD) PMD, which was readily detected from an examination of data distribution. The PMD data were commonly right-skewed, suggesting that the median can be a better estimate of individual PMD than the mean. Repeated measures ANOVA using the median values revealed significant hole-to-hole distance, and hand dominance effects, suggesting that these need to be fixed in the accurate evaluation of PMD. The gender effect was non-significant. Performance consistency was also evaluated by the use of quartile variation coefficient values, which revealed no gender, hole-to-hole, and hand dominance effects. The measurement reliability was further examined using interclass correlation obtained from 14 subjects who performed the 25 and 125 mm hole distance tasks at two 7-10 days separate test sessions. Inter-class correlation values between the two tests showed fair reliability for PMD (0.65-0.75), and for HRD (0.77-0.94). We concluded that a sensor peg board developed in the present study could provide accurate (excluding tester’s errors), and precise (at a millisecond rate) time information of peg movement separated from that used for hand movement. It could also easily detect and automatically exclude erroneous execution data from his/her standard data. These would lead to a better evaluation of hand dexterity function compared to the widely used conventional used peg boards.

Keywords: hand, dexterity test, peg movement time, performance consistency

Procedia PDF Downloads 103