Search results for: anti apoptotic drug
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3892

Search results for: anti apoptotic drug

1882 Comparison of the Use of Vaccines or Drugs against Parasitic Diseases

Authors: H. Al-Khalaifa, A. Al-Nasser

Abstract:

The viewpoint towards the use of drugs or vaccines against avian parasitic diseases is one of the most striking challenges in avian medical parasitology. This includes many difficulties associated with drug resistance and in developing prophylactic vaccines. In many instances, the potential success of a vaccination in controlling parasitic diseases in poultry is well-documented. However, some medical, technical and financial limitations are still paramount. On the other hand, chemotherapy is not very well-recommended due to a number of medical limitations. But in the absence of an effective vaccine, drugs are used against parasitic diseases. This paper sheds light on some the advantages and disadvantages of using vaccination and drugs in controlling parasitic diseases in poultry species. The usage of chemotherapeutic drugs is discussed with some examples. Then, more light will be shed on using vaccines as a potentially effective and promising control tool.

Keywords: drugs, parasitology, poultry, vaccines

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1881 Evaluation of Functional Properties of Protein Hydrolysate from the Fresh Water Mussel Lamellidens marginalis for Nutraceutical Therapy

Authors: Jana Chakrabarti, Madhushrita Das, Ankhi Haldar, Roshni Chatterjee, Tanmoy Dey, Pubali Dhar

Abstract:

High incidences of Protein Energy Malnutrition as a consequence of low protein intake are quite prevalent among the children in developing countries. Thus prevention of under-nutrition has emerged as a critical challenge to India’s developmental Planners in recent times. Increase in population over the last decade has led to greater pressure on the existing animal protein sources. But these resources are currently declining due to persistent drought, diseases, natural disasters, high-cost of feed, and low productivity of local breeds and this decline in productivity is most evident in some developing countries. So the need of the hour is to search for efficient utilization of unconventional low-cost animal protein resources. Molluscs, as a group is regarded as under-exploited source of health-benefit molecules. Bivalve is the second largest class of phylum Mollusca. Annual harvests of bivalves for human consumption represent about 5% by weight of the total world harvest of aquatic resources. The freshwater mussel Lamellidens marginalis is widely distributed in ponds and large bodies of perennial waters in the Indian sub-continent and well accepted as food all over India. Moreover, ethno-medicinal uses of the flesh of Lamellidens among the rural people to treat hypertension have been documented. Present investigation thus attempts to evaluate the potential of Lamellidens marginalis as functional food. Mussels were collected from freshwater ponds and brought to the laboratory two days before experimentation for acclimatization in laboratory conditions. Shells were removed and fleshes were preserved at- 20oC until analysis. Tissue homogenate was prepared for proximate studies. Fatty acids and amino acids composition were analyzed. Vitamins, Minerals and Heavy metal contents were also studied. Mussel Protein hydrolysate was prepared using Alcalase 2.4 L and degree of hydrolysis was evaluated to analyze its Functional properties. Ferric Reducing Antioxidant Power (FRAP) and DPPH Antioxidant assays were performed. Anti-hypertensive property was evaluated by measuring Angiotensin Converting Enzyme (ACE) inhibition assay. Proximate analysis indicates that mussel meat contains moderate amount of protein (8.30±0.67%), carbohydrate (8.01±0.38%) and reducing sugar (4.75±0.07%), but less amount of fat (1.02±0.20%). Moisture content is quite high but ash content is very low. Phospholipid content is significantly high (19.43 %). Lipid constitutes, substantial amount of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) which have proven prophylactic values. Trace elements are found present in substantial amount. Comparative study of proximate nutrients between Labeo rohita, Lamellidens and cow’s milk indicates that mussel meat can be used as complementary food source. Functionality analyses of protein hydrolysate show increase in Fat absorption, Emulsification, Foaming capacity and Protein solubility. Progressive anti-oxidant and anti-hypertensive properties have also been documented. Lamellidens marginalis can thus be regarded as a functional food source as this may combine effectively with other food components for providing essential elements to the body. Moreover, mussel protein hydrolysate provides opportunities for utilizing it in various food formulations and pharmaceuticals. The observations presented herein should be viewed as a prelude to what future holds.

Keywords: functional food, functional properties, Lamellidens marginalis, protein hydrolysate

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1880 Audio-Visual Entrainment and Acupressure Therapy for Insomnia

Authors: Mariya Yeldhos, G. Hema, Sowmya Narayanan, L. Dhiviyalakshmi

Abstract:

Insomnia is one of the most prevalent psychological disorders worldwide. Some of the deficiencies of the current treatments of insomnia are: side effects in the case of sleeping pills and high costs in the case of psychotherapeutic treatment. In this paper, we propose a device which provides a combination of audio visual entrainment and acupressure based compression therapy for insomnia. This device provides drug-free treatment of insomnia through a user friendly and portable device that enables relaxation of brain and muscles, with certain advantages such as low cost, and wide accessibility to a large number of people. Tools adapted towards the treatment of insomnia: -Audio -Continuous exposure to binaural beats of a particular frequency of audible range -Visual -Flash of LED light -Acupressure points -GB-20 -GV-16 -B-10

Keywords: insomnia, acupressure, entrainment, audio-visual entrainment

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1879 Development and Validation of a Green Analytical Method for the Analysis of Daptomycin Injectable by Fourier-Transform Infrared Spectroscopy (FTIR)

Authors: Eliane G. Tótoli, Hérida Regina N. Salgado

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Daptomycin is an important antimicrobial agent used in clinical practice nowadays, since it is very active against some Gram-positive bacteria that are particularly challenges for the medicine, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). The importance of environmental preservation has receiving special attention since last years. Considering the evident need to protect the natural environment and the introduction of strict quality requirements regarding analytical procedures used in pharmaceutical analysis, the industries must seek environmentally friendly alternatives in relation to the analytical methods and other processes that they follow in their routine. In view of these factors, green analytical chemistry is prevalent and encouraged nowadays. In this context, infrared spectroscopy stands out. This is a method that does not use organic solvents and, although it is formally accepted for the identification of individual compounds, also allows the quantitation of substances. Considering that there are few green analytical methods described in literature for the analysis of daptomycin, the aim of this work was the development and validation of a green analytical method for the quantification of this drug in lyophilized powder for injectable solution, by Fourier-transform infrared spectroscopy (FT-IR). Method: Translucent potassium bromide pellets containing predetermined amounts of the drug were prepared and subjected to spectrophotometric analysis in the mid-infrared region. After obtaining the infrared spectrum and with the assistance of the IR Solution software, quantitative analysis was carried out in the spectral region between 1575 and 1700 cm-1, related to a carbonyl band of the daptomycin molecule, and this band had its height analyzed in terms of absorbance. The method was validated according to ICH guidelines regarding linearity, precision (repeatability and intermediate precision), accuracy and robustness. Results and discussion: The method showed to be linear (r = 0.9999), precise (RSD% < 2.0), accurate and robust, over a concentration range from 0.2 to 0.6 mg/pellet. In addition, this technique does not use organic solvents, which is one great advantage over the most common analytical methods. This fact contributes to minimize the generation of organic solvent waste by the industry and thereby reduces the impact of its activities on the environment. Conclusion: The validated method proved to be adequate to quantify daptomycin in lyophilized powder for injectable solution and can be used for its routine analysis in quality control. In addition, the proposed method is environmentally friendly, which is in line with the global trend.

Keywords: daptomycin, Fourier-transform infrared spectroscopy, green analytical chemistry, quality control, spectrometry in IR region

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1878 Refractory Visceral Leishmaniasis Responding to Second-Line Therapy

Authors: Preet Shah, Om Shrivastav

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Introduction : In India, Leishmania donovani is the only parasite causing Leishmaniasis. The parasite infects the reticuloendothelial system and is found in the bone marrow, spleen and liver. Treatment of choice is amphotericin-B with sodium stibogluconate being an alternative. Miltefosine is useful in refractory cases. In our case, Leishmaniasis occurred in a person residing in western India (which is quite rare) and it failed to respond to two different drugs (again an uncommon feature) before it finally responded to a third one. Description: A 50 year old lady, a resident of western India, with no history of recent travel, presented with an ulcer on the left side of the nose since 8 months. She was apparently alright 8 months back, when she noticed a small ulcerated lesion on the left ala of the nose which was immediately biopsied. The biopsy revealed amastigotes of Leishmania for which she was administered intra-lesional sodium stibogluconate for 1 month (4 doses every 8 days).Despite this, there was no regression of the ulcer and hence she presented to us for further management. On examination, her vital parameters were normal. Barring an ulcer on the left side of the nose, rest of the examination findings were unremarkable. Complete blood count was normal. Ultrasound abdomen showed hepatomegaly. PET-CT scan showed increased metabolic activity in left ala of nose, hepatosplenomegaly and increased metabolic activity in spleen and bone marrow. Bone marrow biopsy was done which showed hypercellular marrow with erythroid preponderance. Considering a diagnosis of leishmaniasis which had so far been unresponsive to sodium stibogluconate, she was started on liposomal amphotericin-B. At the time of admission, her creatinine level was normal, but it started rising with the administration of liposomal amphotericin-B, hence the dose was reduced. Despite this, creatinine levels did not improve, and she started developing hypokalemia and hypomagnesemia as side effects of the drug, hence further reductions in the dosage were made. Despite a total of 3 weeks of liposomal amphotericin-B, there was no improvement in the ulcer. As had so far failed to respond to sodium stibogluconate and liposomal amphotericin-B, it was decided to start her on miltefosine. She received the miltefosine for a total of 12 weeks. At the end of this duration, there was a marked regression of the cutaneous lesion. Conclusion: Refractoriness to amphotericin-B in leishmaniasis may be seen in up to 5 % cases. Here, an alternative drug such as miltefosine is useful and hence we decided to use it, to which she responded adequately. Furthermore, although leishmaniasis is common in the eastern part of India, it is a relatively unknown entity in the western part of the country with the occurrence being very rare. Because of these 2 reasons, we consider our case to be a unique one.

Keywords: amphotericin-b, leishmaniasis, miltefosine, tropical diseases

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1877 Zoledronic Acid with Neoadjuvant Chemotherapy in Advanced Breast Cancer Prospective Study 2011–2014

Authors: S. Sakhri

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Background: The use of Zoledronic acid (ZA) is an established place in the treatment of malignant tumors with a predilection for the skeleton of interest (in particular metastasis). Although the main target of Zoledronic acid was osteoclasts, there are preclinical data suggest that Zoledronic acid may have an antitumor effect on cells other than osteoclasts, including tumor cells. Antitumor activity, including the inhibition of tumor cell growth and the induction of apoptosis of tumor cells, inhibition of tumor cell adhesion and invasion, and anti-angiogenic effects have been demonstrated. Methods. From (2012 to 2014), 438 patients were included respondents the inclusion criteria, respectively. This is a prospective study over a 4 year period. Of all patients (N=438), 432 received neoadjuvant chemotherapy with Zoledronic acid. The primary end point was the pathologic complete response in advancer breast cancer stage. The secondary end point is to evaluate Clinical response according to RECIST criteria; estimate the bone density before and at the end of chemotherapy in women with locally advanced breast cancer, Toxicity Evaluation and Overall survival using Kaplan-Meier and log test. Result: The Objective response rate was 97% after (C4) with 3% stabilizations and 99, 3% of which 0.7% C8 after stabilization. The clinical complete response was 28% after C4 respectively, and 46.8% after C8, the pathologic complete response rate was 40.13% according to the classification Sataloff. We observed that the pathologic complete response rate was the most raised in the group including Her2 (luminal Her2 and Her2) the lowest in the triple negative group as classified by Sataloff. We found that the pCR is significantly higher in the age group (35-50 years) with 53.17%. Those who have more than 50 years in 2nd place with 27.7% and the lower in young woman 35 years pCR was 19%, not statistically significant, -The pCR was also in favor of the menopausal group in 51, 4%, and 48, 55% for non-menopausal women. The average duration of overall survival was also significantly in the subgroup (Luminal -Her2, Her2) compared with triple negative. It is 47.18 months in the luminal group vs. 38.95 in the triple negative group. -Was observed in our study a difference in quality of life between (C1) was the admission of the patient, and after (C8), we found an increase in general signs and a deterioration in the psychological state C1, in contrast to the C8 these general signs and mental status improves, up to 12, and 24 months. Conclusion The results of this study suggest that the addition of ZA to néoadjuvant CT has potential anti-cancer benefit in patients (Luminal -Her2, Her2) compared with triple negative with or without menopause status.

Keywords: HER2+, RH+, breast cancer, tyrosine kinase

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1876 Secret Security Smart Lock Using Artificial Intelligence Hybrid Algorithm

Authors: Vahid Bayrami Rad

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Ever since humans developed a collective way of life to the development of urbanization, the concern of security has always been considered one of the most important challenges of life. To protect property, locks have always been a practical tool. With the advancement of technology, the form of locks has changed from mechanical to electric. One of the most widely used fields of using artificial intelligence is its application in the technology of surveillance security systems. Currently, the technologies used in smart anti-theft door handles are one of the most potential fields for using artificial intelligence. Artificial intelligence has the possibility to learn, calculate, interpret and process by analyzing data with the help of algorithms and mathematical models and make smart decisions. We will use Arduino board to process data.

Keywords: arduino board, artificial intelligence, image processing, solenoid lock

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1875 Synthesis and Anticholinesterase Activity of Carvacrol Derivatives

Authors: Fatih Sonmez

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease and it is the most common form of dementia that affects aged people. Acetylcholinesterase is a hydrolase involved in the termination of impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter ACh in the central and peripheral nervous system. Carvacrol (5-iso-propyl-2-methyl-phenol) is a main bioactive monoterpene isolated from many medicinal herbs, such as Thymus vulgaris, Monarda punctate and Origanum vulgare spp. It is known that carvacrol has been widely used as an active anti-inflammatory ingredient, which can inhibit the isoproterenol induced inflammation in myocardial infarcted rats. In this paper, a series of 12 carvacrol substituted carbamate derivatives (2a-l) was synthesized and their inhibitory activities on AChE and BuChE were evaluated. Among them, 2d exhibited the strongest inhibition against AChE with an IC50 value of 2.22 µM, which was 130-fold more than that of carvacrol (IC50 = 288.26 µM).

Keywords: Acetylcholinesterase, Butyrylcholinesterase, Carbamate, Carvacrol

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1874 Formulation and Characterization of Active Edible Films from Cassava Starch for Snacks and Savories

Authors: P. Raajeswari, S. M. Devatha, S. Yuvajanani, U. Rashika

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Edible food packaging are the need of the hour to save life on land and under water by eliminating waste cycle and replacing Single Use Plastics at grass root level as it can be eaten or composted as such. Cassava (Manihot esculenta) selected for making edible films are rich source of starch, and also it exhibit good sheeting propertiesdue to the high amylose: amylopectin content. Cassava starch was extracted by manual method at a laboratory scale and yielded 65 per cent. Edible films were developed by adding food grade plasticizers and water. Glycerol showed good plasticizing property as compared to sorbitol and polylactic acid in both manual (petri dish) and machine (film making machine) production. The thickness of the film is 0.25±0.03 mm. Essential oil and components from peels like pomegranate, orange, pumpkin, onion, and banana brat, and herbs like tulsi and country borage was extracted through the standardized aqueous and alkaline method. In the standardized film, the essential oil and components from selected peel and herbs were added to the casting solution separately and casted the film. It was added to improve the anti-oxidant, anti-microbial and optical properties. By inclusion of extracts, it reduced the bubble formation while casting. FTIR, Water Vapor and Oxygen Transmission Rate (WVTR and OTR), tensile strength, microbial load, shelf life, and degradability of the films were done to analyse the mechanical property of the standardized films. FTIR showed the presence of essential oil. WVTR and OTR of the film was improved after inclusion of essential oil and extracts from 1.312 to 0.811 cm₃/m₂ and 15.12 to 17.81 g/ m₂.d. Inclusion of essential oil from herbs showed better WVTR and OTR than the inclusion of peel extract and standard. Tensile strength and Elongation at break has not changed by essential oil and extracts at 0.86 ± 0.12 mpa and 14 ± 2 at 85 N force. By inclusion of extracts, an optical property of the film enhanced, and it increases the appearance of the packaging material. The films were completely degraded on 84thdays and partially soluble in water. Inclusion of essential oil does not have impact on degradability and solubility. The microbial loads of the active films were decreased from 15 cfu/gm to 7 cfu/gm. The films can be stored at frozen state for 24 days and 48 days at atmospheric temperature when packed with South Indian snacks and savories.

Keywords: active films, cassava starch, plasticizer, characterization

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1873 Unraveling the Gut-Brain Connection in Alcohol Use Disorder: Microbiome Dysbiosis and Probiotic Therapy as Emerging Treatment Pathways

Authors: Noah Emil Glisik

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Alcohol use disorder (AUD) presents significant health challenges worldwide and is particularly concerning in Slovenia, where high alcohol consumption contributes to elevated rates of comorbidities, including depression and suicide. This review examines emerging evidence linking gut microbiome dysbiosis to AUD, exploring whether gut microbiome alterations merely result from alcohol use or actively contribute to the persistence of addiction. Additionally, it discusses how microbial changes may influence psychological symptoms, including anxiety and depressive states, which are closely associated with suicidality in this population. To address gaps in existing research, a systematic literature search was conducted through PubMed, Web of Science, and ScienceDirect. Inclusion criteria focused on studies examining gut microbiome changes in AUD, particularly those assessing gut-brain axis interactions and microbial species impacting inflammation and neurotransmitter pathways. Studies were excluded if they lacked peer review or did not specifically assess microbiome effects on mental health outcomes. A qualitative literature review approach was applied, synthesizing findings into key themes on microbial changes, neuroinflammatory pathways, and treatment implications. Data were organized into tables to provide a clear comparison of microbiota alterations across studies, highlighting specific bacterial species and their potential effects on AUD. This review emphasizes patterns in AUD patients, where reductions in anti-inflammatory species, such as Faecalibacterium prausnitzii and Roseburia intestinalis, coincide with increases in pro-inflammatory bacteria like Enterococcus faecalisand Lactobacillus rhamnosus. These shifts contribute to increased gut permeability and systemic inflammation, potentially influencing the kynurenine pathway, which is linked to depressive symptoms and elevated alcohol cravings. Furthermore, the review explores the potential of probiotic therapies targeting these microbial imbalances as adjunctive treatments for AUD, particularly those focusing on strains that support anti-inflammatory pathways and gut barrier integrity. Restoring microbial homeostasis through probiotics or fecal microbiota transplantation may not only reduce inflammation but also alleviate mental health symptoms associated with addiction, including suicidality. The findings underscore the need for further clinical trials assessing microbiome-targeted therapies as innovative, multifaceted approaches to AUD treatment in Slovenia and beyond.

Keywords: alcohol use disorder, gut-brain axis, microbiome dysbiosis, probiotic therapy.

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1872 Conservative and Surgical Treatment of Antiresorptive Drug-Related Osteonecrosis of the Jaw with Ultrasonic Piezoelectric Bone Surgery under Polyvinylpyrrolidone Iodine Irrigation: A Case Series of 13 Treated Sites

Authors: Esra Yuce, Isil D. S. Yamaner, Murude Yazan

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Aims and objective: Antiresorptive agents including bisphosphonates and denosumab as strong suppressors of osteoclasts are the most commonly used antiresorptive medications for the treatment of osteoporosis which counteract the negative quantitative alteration of trabecular and cortical bone by inhibition of bone turnover. Oral bisphosphonate therapy for the treatment of osteopenia, osteoporosis or Paget's disease is associated with the low-grade risk of osteonecrosis of the jaw, while higher-grade risk is associated with receiving intravenous bisphosphonates therapy in the treatment of multiple myeloma and bone metastases. On the other hand, there has been a remarkable increase in incidences of antiresorptive related osteonecrosis of the jaw (ARONJ) in oral bisphosphonate users. This clinical presentation will evaluate the healing outcomes via piezoelectric bone surgery under the irrigation of PVP-I solution irrigation in patients received bisphosphonate therapy. Material-Method: The study involved 8 female and 5 male patients that have been treated for ARONJ. Among 13 necrotic sites, 9 were in the mandible and 4 were in the maxilla. All of these 13 patients treated with surgical debridement via piezoelectric bone surgery under irrigation by solution with 3% PVP-I concentration in combination with long-term antibiotic therapy and 5 also underwent removal of mobile segments of bony sequestrum. All removable prosthesis in 8 patients were relined with soft liners during the healing periods in order to eliminate chronic minor traumas. Results: All patients were on oral bisphosphonate therapy for at least 2 years and 5 of which had received intravenous bisphosphonates up to 1 year before therapy with oral bisphosphonates was started. According to the AAOMS staging system, four cases were stage II, eight cases were stage I, and one case was stage III. The majority of lesions were identified at sites of dental prostheses (38%) and dental extractions (62%). All patients diagnosed with ARONJ stage I had used unadjusted removable prostheses. No recurrence of the symptoms was observed during the present follow-up (9–37 months). Conclusion: Despite their confirmed effectiveness, the prevention and treatment of osteonecrosis of the jaw secondary to oral bisphosphonate therapy remain major medical challenges. Treatment with piezoelectric bone surgery with irrigation of povidone-iodine solution was effective for management of bisphosphonate-related osteonecrosis of the jaw. Taking precautions for patients treated with oral bisphosphonates, especially also denture users, may allow for a reduction in the rate of developing osteonecrosis of the maxillofacial region.

Keywords: antiresorptive drug related osteonecrosis, bisphosphonate therapy, piezoelectric bone surgery, povidone iodine

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1871 The Influence of the Variety and Harvesting Date on Haskap Composition and Anti-Diabetic Properties

Authors: Aruma Baduge Kithma Hansanee De Silva

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Haskap (Lonicera caerulea L.), also known as blue honeysuckle, is a recently commercialized berry crop in Canada. Haskap berries are rich in polyphenols, including anthocyanins, which are known for potential health-promoting effects. Cyanidin-3-O-glucoside (C3G) is the most prominent anthocyanin of haskap berries. Recent literature reveals the efficacy of C3G in reducing the risk of type 2 diabetes (T2D), which has become an increasingly common health issue around the world. The T2D is characterized as a metabolic disorder of hyperglycemia and insulin resistance. It has been demonstrated that C3G has anti-diabetic effects in various ways, including improvement in insulin sensitivity, and inhibition of activities of carbohydrate-hydrolyzing enzymes, including alpha-amylase and alpha-glucosidase. The goal of this study was to investigate the influence of variety and harvesting date on haskap composition, biological properties, and antidiabetic properties. The polyphenolic compounds present in four commercially grown haskap cultivars, Aurora, Rebecca, Larissa and Evie among five harvesting stages (H1-H5), were extracted separately in 80% ethanol and analyzed to characterize their phenolic profiles. The haskap berries contain different types of polyphenols including flavonoids and phenolic acids. Anthocyanin is the major type of flavonoid. C3G is the most prominent type of anthocyanin, which accounts for 79% of total anthocyanin in all extracts. The variety Larissa at H5 contained the highest average C3G content, and its ethanol extract had the highest (1212.3±63.9 mg/100g FW) while, Evie at H1 contained the lowest C3G content (96.9±40.4 mg/100g FW). The average C3G content of Larissa from H1 – H5 varies from 208 – 1212 mg/100g FW. Quarcetin-3-Rutinoside (Q3Rut) is the major type of flavonol and highest is observed in Rebecca at H4 (47.81 mg/100g FW). The haskap berries also contained phenolic acids, but approximately 95% of the phenolic acids consisted of chlorogenic acid. The cultivar Larissa has a higher level of anthocyanin than the other four cultivars. The highest total phenolic content is observed in Evie at H5 (2.97±1.03 mg/g DW) while the lowest in Rebecca at H1 (1.47±0.96 mg/g DW). The antioxidant capacity of Evie at H5 was higher (14.40±2.21 µmol TE/ g DW) among other cultivars and the lowest observed in Aurora at H3 (5.69±0.34 µmol TE/ g DW). Furthermore, Larissa H5 shows the greatest inhibition of carbohydrate-hydrolyzing enzymes including alpha-glucosidase and alpha-amylase. In conclusion Larissa, at H5 demonstrated highest polyphenol composition and antidiabetic properties.

Keywords: anthocyanin, cyanidin-3-O-glucoside, haskap, type 2 diabetes

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1870 Protective Role of Autophagy Challenging the Stresses of Type 2 Diabetes and Dyslipidemia

Authors: Tanima Chatterjee, Maitree Bhattacharyya

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The global challenge of type 2 diabetes mellitus is a major health concern in this millennium, and researchers are continuously exploring new targets to develop a novel therapeutic strategy. Type 2 diabetes mellitus (T2DM) is often coupled with dyslipidemia increasing the risks for cardiovascular (CVD) complications. Enhanced oxidative and nitrosative stresses appear to be the major risk factors underlying insulin resistance, dyslipidemia, β-cell dysfunction, and T2DM pathogenesis. Autophagy emerges to be a promising defense mechanism against stress-mediated cell damage regulating tissue homeostasis, cellular quality control, and energy production, promoting cell survival. In this study, we have attempted to explore the pivotal role of autophagy in T2DM subjects with or without dyslipidemia in peripheral blood mononuclear cells and insulin-resistant HepG2 cells utilizing flow cytometric platform, confocal microscopy, and molecular biology techniques like western blotting, immunofluorescence, and real-time polymerase chain reaction. In the case of T2DM with dyslipidemia higher population of autophagy, positive cells were detected compared to patients with the only T2DM, which might have resulted due to higher stress. Autophagy was observed to be triggered both by oxidative and nitrosative stress revealing a novel finding of our research. LC3 puncta was observed in peripheral blood mononuclear cells and periphery of HepG2 cells in the case of the diabetic and diabetic-dyslipidemic conditions. Increased expression of ATG5, LC3B, and Beclin supports the autophagic pathway in both PBMC and insulin-resistant Hep G2 cells. Upon blocking autophagy by 3-methyl adenine (3MA), the apoptotic cell population increased significantly, as observed by caspase‐3 cleavage and reduced expression of Bcl2. Autophagy has also been evidenced to control oxidative stress-mediated up-regulation of inflammatory markers like IL-6 and TNF-α. To conclude, this study elucidates autophagy to play a protective role in the case of diabetes mellitus with dyslipidemia. In the present scenario, this study demands to have a significant impact on developing a new therapeutic strategy for diabetic dyslipidemic subjects by enhancing autophagic activity.

Keywords: autophagy, apoptosis, dyslipidemia, reactive oxygen species, reactive nitrogen species, Type 2 diabetes

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1869 Antimicrobial Activity of 2-Nitro-1-Propanol and Lauric Acid against Gram-Positive Bacteria

Authors: Robin Anderson, Elizabeth Latham, David Nisbet

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Propagation and dissemination of antimicrobial resistant and pathogenic microbes from spoiled silages and composts represents a serious public health threat to humans and animals. In the present study, the antimicrobial activity of the short chain nitro-compound, 2-nitro-1-propanol (9 mM) as well as the medium chain fatty acid, lauric acid, and its glycerol monoester, monolaurin, (each at 25 and 17 µmol/mL, respectfully) were investigated against select pathogenic and multi-drug resistant antimicrobial resistant Gram-positive bacteria common to spoiled silages and composts. In an initial study, we found that growth rates of a multi-resistant Enterococcus faecalis (expressing resistance against erythromycin, quinupristin/dalfopristin and tetracycline) and Staphylococcus aureus strain 12600 (expressing resistance against erythromycin, linezolid, penicillin, quinupristin/dalfopristin and vancomycin) were more than 78% slower (P < 0.05) by 2-nitro-1-propanol treatment during culture (n = 3/treatment) in anaerobically prepared ½ strength Brain Heart Infusion broth at 37oC when compared to untreated controls (0.332 ± 0.04 and 0.108 ± 0.03 h-1, respectively). The growth rate of 2-nitro-1-propanol-treated Listeria monocytogenes was also decreased by 96% (P < 0.05) when compared to untreated controls cultured similarly (0.171 ± 0.01 h-1). Maximum optical densities measured at 600 nm were lower (P < 0.05) in 2-nitro-1-propanol-treated cultures (0.053 ± 0.01, 0.205 ± 0.02 and 0.041 ± 0.01, respectively) than in untreated controls (0.483 ± 0.02, 0.523 ± 0.01 and 0.427 ± 0.01, respectively) for E. faecalis, S. aureus and L. monocytogenes, respectively. When tested against mixed microbial populations during anaerobic 24 h incubation of spoiled silage, significant effects of treatment with 1 mg 2-nitro-1-propanol (approximately 9.5 µmol/g) or 5 mg lauric acid/g (approximately 25 µmol/g) on populations of wildtype Enterococcus and Listeria were not observed. Mixed populations treated with 5 mg monolaurin/g (approximately 17 µmol/g) had lower (P < 0.05) viable cell counts of wildtype enterococci than untreated controls after 6 h incubation (2.87 ± 1.03 versus 5.20 ± 0.25 log10 colony forming units/g, respectively) but otherwise significant effects of monolaurin were not observed. These results reveal differential susceptibility of multi-drug resistant enterococci and staphylococci as well as L. monocytogenes to the inhibitory activity of 2-nitro-1-propanol and the medium chain fatty acid, lauric acid and its glycerol monoester, monolaurin. Ultimately, these results may lead to improved treatment technologies to preserve the microbiological safety of silages and composts.

Keywords: 2-nitro-1-propanol, lauric acid, monolaurin, gram positive bacteria

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1868 Evaluation of Antimicrobial Activity of Phenolic Compounds Extracted from Jordanian Juglans regia L.

Authors: Hamoud Alshammari, Adnan Almezani, Hamdan Alshammari, Faris Alharbi

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In this study we have examined of antimicrobial activity for unripe Juglan Regia phenolic extracts against a wide range of pathogenic microorganisms. Walnut (Juglans regia L.) is a member of Juglandaceae family used as a remedy in folk medicine. Leaves, barks, fruits and husk (peel) reported to harbor distinctive medical effect. In our study, we examined the anti-microbial effect against a set of gram positive and negative bacteria and even we have tested them against eukaryotic candida strains in a concentration gradual manner. Ethyl acetate extract of J. regia had the best antibacterial activity when compared with ciprofloxacin. The Minimum inhibition concentration for S. aureus, P. aerogenosa and S. epidermidis MIC was 0.85 mg/mL.

Keywords: antimicrobial, J. regia, S. aureus, phytochemistry

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1867 Poisoning in Morocco: Evolution and Risk Factors

Authors: El Khaddam Safaa, Soulaymani Abdelmajid, Mokhtari Abdelghani, Ouammi Lahcen, Rachida Soulaymani-Beincheikh

Abstract:

The poisonings represent a problem of health in the world and Morocco, The exact dimensions of this phenomenon are still poorly recorded that we see the lack of exhaustive statistical data. The objective of this retrospective study of a series of cases of the poisonings declared at the level of the region of Tadla-Azilal and collected by the Moroccan Poison Control and Pharmacovigilance Center. An epidemiological profile of the poisonings was to raise, to determine the risk factors influencing the vital preview of the poisoned And to follow the evolution of the incidence, the lethality, and the mortality. During the period of study, we collected and analyzed 9303 cases of poisonings by different incriminated toxic products with the exception of the scorpion poisonings. These poisonings drove to 99 deaths. The epidemiological profile which we raised, showed that the poisoned were of any age with an average of 24.62±16.61 years, The sex-ratio (woman/man) was 1.36 in favor of the women. The difference between both sexes is highly significant (χ2 = 210.5; p<0,001). Most of the poisoned which declared to be of urban origin (60.5 %) (χ2=210.5; p<0,001). Carbon monoxide was the most incriminated among the cases of poisonings (24.15 %), them putting in head, followed by some pesticides and farm produces (21.44 %) and food (19.95 %). The analysis of the risk factors showed that the grown-up patients whose age is between 20 and 74 years have twice more risk of evolving towards the death (RR=1,57; IC95 % = 1,03-2,38) than the other age brackets, so the male genital organ was the most exposed (explained) to the death that the female genital organ (RR=1,59; IC95 % = 1,07-2,38) The patients of rural origin had presented 5 times more risk (RR=4,713; IC95 % = 2,543-8,742). Poisoned by the mineral products had presented the maximum of risk on the vital preview death (RR=23,19, IC95 % = 2,39-224,1). The poisonings by pesticides produce a risk of 9 (RR=9,31; IC95 % = 6,10-14,18). The incidence was 3,3 cases of 10000 inhabitants, and the mortality was 0,004 cases of 1000 inhabitants (that is 4 cases by 1000 000 inhabitants). The rate of lethality registered annually was 10.6 %. The evolution of the indicators of health according to the years showed that the rate of statement measured by the incidence increased by a significant way. We also noted an improvement in the coverage which (who) ended up with a decrease in the rate of the lethality and the mortality during last years. The fight anti-toxic is a work of length time. He asks for a lot of work various levels. It is necessary to attack the delay accumulated by our country on the various legal, institutional and technical aspects. The ideal solution is to develop and to set up a national strategy.

Keywords: epidemiology, poisoning, risk factors, indicators of health, Tadla-Azilal grated by anti-toxic fight

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1866 Examination of Calpurnia Aurea Seed Extract Activity Against Hematotoxicity and Hepatotoxicity in HAART Drug Induced Albino Wistar Rat

Authors: Haile Nega Mulata, Seifu Daniel, Umeta Melaku, Wendwesson Ergete, Natesan Gnanasekaran

Abstract:

Background: In Ethiopia, medicinal plants have been used for various human and animal diseases. In this study, we have examined the potential effect of hydroethanolic extract of Calpurnia aurea seed against hepatotoxicity and haematotoxicity induced by Highly Active Antiretroviral Therapy (HAART) drugs in Albino Wistar rats. Methods: We collected Matured dried seeds of Calpurnia aurea from northern Ethiopia (south Tigray and south Gondar) in June 2013. The powder of the dried seed sample was macerated with 70% ethanol and dried using rotavapor. We have investigated the Preliminary phytochemical tests and in-vitro antioxidant properties. Then, we induced toxicity with HAART drugs and gave the experimental animals different doses of the crude extract orally for thirty-five days. On the 35th day, the animals were fasted overnight and sacrificed by cervical dislocation. We collected the blood samples by cardiac puncture. We excised the liver and brain tissues for further histopathological studies. Subsequently, we analysed serum levels of the liver enzymes- Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Total Bilirubin, and Serum Albumin, using commercial kits in Cobas Integra 400 Plus Roche Analyzer Germany. We have also assessed the haematological profile using an automated haematology Analyser (Sysmex KX-2IN). Results: A significant (P<0.05) decrease in serum enzymes (ALT and AST) and total bilirubin were observed in groups that received the highest dose (300mg/kg) of the seed extract. And significant (P<0.05) elevation of total red blood cell count, haemoglobin, and hematocrit percentage was observed in the groups that received the seed extract compared to the HAART-treated groups. The WBC count mean values showed a statistically significant increase (p<0.05) in groups that received HAART and 200 and 300mg/kg extract, respectively. The histopathological observations also showed that the oral administration of varying doses of the crude extract of the seed reversed to a normal state. Conclusion: The hydroethanolic extract of the Calpurnia aurea seed lowered the hepatotoxicity and haematotoxicity in a dose-dependent manner. The antioxidant properties of the Calpurnia aurea seed extract may have possible protective effects against the drug's toxicity.

Keywords: calpurnia aurea, hepatotoxicity, haematotoxicity, antioxidant, histopathology, HAART

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1865 Detecting of Crime Hot Spots for Crime Mapping

Authors: Somayeh Nezami

Abstract:

The management of financial and human resources of police in metropolitans requires many information and exact plans to reduce a rate of crime and increase the safety of the society. Geographical Information Systems have an important role in providing crime maps and their analysis. By using them and identification of crime hot spots along with spatial presentation of the results, it is possible to allocate optimum resources while presenting effective methods for decision making and preventive solutions. In this paper, we try to explain and compare between some of the methods of hot spots analysis such as Mode, Fuzzy Mode and Nearest Neighbour Hierarchical spatial clustering (NNH). Then the spots with the highest crime rates of drug smuggling for one province in Iran with borderline with Afghanistan are obtained. We will show that among these three methods NNH leads to the best result.

Keywords: GIS, Hot spots, nearest neighbor hierarchical spatial clustering, NNH, spatial analysis of crime

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1864 Effect of Long-Term Boron Exposure on Liver Structure of Adult Male Albino Rats and a Possible Role of Vitamin C

Authors: Ola Abdel-Tawab Hussein

Abstract:

Background: Boron is a naturally occurring agent and an essential trace element of human, animals and higher plants. It is released in the form of boric acid (BA) that is water soluble and biolologically available. Its largest uses are in glass, detergents, agriculture, leather tanning industries, cosmetics, photographic materials, soaps and cleaners. Human consume daily few milligrams in the water, fruits and vegetables. High doses of boron had been recorded to be developmental and reproductive toxin in animals(Only few studies on human had investigated the health effects associated with exposure to boron. Vitamin C is a major water soluble non-enzymatic antioxidant, acts to overcome the oxidative stress. Aim of the work: However , the liver is exposed to toxic substances that are absorbed, degraded or conjugated there were little information exists about the effects of boron that it would specifically have in the liver tissue of experimental rats. So the present work aimed to study the effects of long-term boron ingestion on histological structural of the liver of adult male albino rats and to evaluate the protective role of vitamin C against induced changes. Material and Methods: 30 adult male albino rats were divided into 3 equal groups; Group I: control, Group II: recieved drinking water containing 55x10-6 gm boron/liter for 90 days and Group III: recieved vitamin C (200mg/Kg.B.W) orally concomitant with boron for the same period. liver specimens were processed for light and electron microscopic(TEM) study. Results: Examination of the liver sections of group II revealed foci of severe dilatation and congestion of central and portal veins with mononuclear cellular infiltration and hepatocellular vacuolation. Increased collagen deposition specially around the portal areas. Marked electrolucent areas in the cytoplasm, heterochromatic nuclei and destroyed organelles of the hepatocytes. Apoptotic cells were observed and decreased lipid content of ito cells. In Group III the co administration of vitamin C improved most of the structural changes of the hepatocytes, Ito cells, increased binucleated cells and decreased collagen fibers deposition. Conclusion: Thus, the long term exposure to boron, induced histological changes on the structure of liver. The co administration of vitamin C improved most of these structural changes.

Keywords: boron, liver, vitamin C, rats

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1863 Offshore Outsourcing: Global Data Privacy Controls and International Compliance Issues

Authors: Michelle J. Miller

Abstract:

In recent year, there has been a rise of two emerging issues that impact the global employment and business market that the legal community must review closer: offshore outsourcing and data privacy. These two issues intersect because employment opportunities are shifting due to offshore outsourcing and some States, like the United States, anti-outsourcing legislation has been passed or presented to retain jobs within the country. In addition, the legal requirements to retain the privacy of data as a global employer extends to employees and third party service provides, including services outsourced to offshore locations. For this reason, this paper will review the intersection of these two issues with a specific focus on data privacy.

Keywords: outsourcing, data privacy, international compliance, multinational corporations

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1862 Disciplinary Problems among Adeyemi College of Education Students in the Ondo State of Nigeria

Authors: Akinyemi Olufunminiyi Akinbobola

Abstract:

This paper analytically discusses the disciplinary problems among Adeyemi College of Education Students in the Ondo State of Nigeria. The paper posits that the causes and types of disciplinary problems experienced by the students are determinacy of disciplinary measures to be taken. The study used a questionnaire titled: Disciplinary Problem Questionnaire (DPQ) to collect data. Five hundred (500) students were randomly sampled in the five schools in the college. The results showed that drug addiction, school curriculum, cultism, peer group influence, overcrowded classroom, political, social, and economic among others are disciplinary problems experienced in the study area. The study made recommendations on how to improve the situation.

Keywords: challenges in higher institutions, disciplinary problems, social vices, students’ indiscipline

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1861 Potential of Comparative Management and Aspects of Its Application in Georgia

Authors: Evgeni Baratashvili, Nino Pailodze, Ana Bolkvadze, Giorgi Sulashvili

Abstract:

At the present stage in our country intensifies cooperation with different business cultures, actively developing the process of implementation of Georgia in the global business system that requires us to develop a specific concept, including in the field of management. With the entry of Georgia into the international community, exchange of experience will only intensify. It is clear that the achievement of goals such as the doubling of the National Product increase the competitiveness of Georgian enterprises can’t be recorded without foreign management experience. On the other hand, knowledge of the areas of comparative management can be used in the process of choosing the path of socio-economic development of Georgia.

Keywords: business cultures, comparative management, corporate culture, Georgian business, Anglo-Saxon model, Georgian civilization, anti-capitalist mentality, culture management

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1860 A Retrospective Study on Causes, Surgery Findings, Results and Follow up of 30 Horses with Colic in Tehran, Iran

Authors: Farajallah Adibhashemi

Abstract:

A retrospective study on causes, surgery findings, results and the follow up of 30 horses with colic in Tehran, Iran. Colic is the main problem horse industry.The causes of colic are related to management like food, sport and medical care. In this study that has been done between 2012-2015 for 30 horses referred to teaching hospital of veterinary medicine faculty of the University of Tehran. Seventy percent of causes was related to management of feeding and twenty percent was for malsporting. The rest of causes was from the anti parasite in bad root. The surgery findings were as follows: 60% displacement of dorsal right and left colon, 20% in impaction of pelvic flexure,10% impaction of the cecum, and 10% impaction of the stomach.

Keywords: horse, colic, Tehran, Iran

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1859 An Analysis of Possible Implications of Patent Term Extension in Pharmaceutical Sector on Indian Consumers

Authors: Anandkumar Rshindhe

Abstract:

Patents are considered as good monopoly in India. It is a mechanism by which the inventor is encouraged to do invention and also to make available to the society at large with a new useful technology. Patent system does not provide any protection to the invention itself but to the claims (rights) which the patentee has identified in relation to his invention. Thus the patentee is granted monopoly to the extent of his recognition of his own rights in the form of utilities and all other utilities of invention are for the public. Thus we find both benefit to the inventor and the public at large that is the ultimate consumer. But developing any such technology is not free of cost. Inventors do a lot of investment in the coming out with a new technologies. One such example if of Pharmaceutical industries. These pharmaceutical Industries do lot of research and invest lot of money, time and labour in coming out with these invention. Once invention is done or process identified, in order to protect it, inventors approach Patent system to protect their rights in the form of claim over invention. The patent system takes its own time in giving recognition to the invention as patent. Even after the grant of patent the pharmaceutical companies need to comply with many other legal formalities to launch it as a drug (medicine) in market. Thus major portion in patent term is unproductive to patentee and whatever limited period the patentee gets would be not sufficient to recover the cost involved in invention and as a result price of patented product is raised very much, just to recover the cost of invent. This is ultimately a burden on consumer who is paying more only because the legislature has failed to provide for the delay and loss caused to patentee. This problem can be effectively remedied if Patent Term extension is done. Due to patent term extension, the inventor gets some more time in recovering the cost of invention. Thus the end product is much more cheaper compared to non patent term extension.The basic question here arises is that when the patent period granted to a patentee is only 20 years and out of which a major portion is spent in complying with necessary legal formalities before making the medicine available in market, does the company with the limited period of monopoly recover its investment made for doing research. Further the Indian patent Act has certain provisions making it mandatory on the part of patentee to make its patented invention at reasonable affordable price in India. In the light of above questions whether extending the term of patent would be a proper solution and a necessary requirement to protect the interest of patentee as well as the ultimate consumer. The basic objective of this paper would be to check the implications of Extending the Patent term on Indian Consumers. Whether it provides the benefits to the patentee, consumer or a hardship to the Generic industry and consumer.

Keywords: patent term extention, consumer interest, generic drug industry, pharmaceutical industries

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1858 Dissatisfaction as a Cause of Social Uprisings: An Empirical Analysis Utilizing the Social Uprisings Composite Indicator

Authors: Sondos Shaheen

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This paper employs a newly constructed composite indicator of social uprisings (SUCI) to analyze the causes of their occurrence. This empirical study is based on an unbalanced panel of 45 countries over the period of 1982–2007. The paper’s contribution to the literature is distinguishing between the causes of violent and nonviolent uprisings. The analysis shows that that certain variables have a significant impact on both violent and nonviolent uprisings in terms of relative SUCI values, for example, ethnic fractionalization and mountainous terrain. Nevertheless, differences between the causes of violent and nonviolent uprisings can be found. For example, life dissatisfaction is related to nonviolent social uprisings, but when life dissatisfaction is accompanied by democratic dissatisfaction, violent social uprisings are more likely.

Keywords: social uprisings, relative deprivation, dissatisfaction, mobilization, anti-government movements, causes

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1857 Current Perspectives of Bemitil Use in Sport

Authors: S. Ivanova, K. Ivanov

Abstract:

Bemitil (2-ethylthiobenzimidazole hydrobromide) is a synthetic adaptogen and actoprotector, with wide-ranging pharmacological activities such as nootropic, antihypoxic, antioxidant, immunostimulant. The intake of Bemitil increases mental and physical performance and could be applied under either normal or extreme conditions. Until 2017 Bemitil was not considered as doping and was used by professional athletes more than 30 years because of its high efficiency and safety. The drug was included in WADA monitoring programme for 2018, and most likely it would be included in WADA Prohibited List for 2019. Usually, a substance/method is included in WADA Prohibited List if it meets any two of the following three criteria: the potential to enhance or enhances sports performance/ potential health risk to the athlete/ violates the spirit of sport. Bemitil has high performance-enhancing potential, but it is also safe- it is controversial whether it should be considered as doping.

Keywords: doping, bemitil, sport, actoprotector

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1856 Immigration Solutions for the United States

Authors: Philip Robert Alldritt

Abstract:

The continuing increase in human migration is at crisis levels in all areas of the planet. The causes are varied, and the risks are high for the migrants. Migration has been ongoing since the beginning of human emergence on the planet, but for the first time in our historic memory has the, migration reached this level of critical mass. The causes are many. Climate collapse, economic opportunity, drug cartel activity, political upheaval, and gang wars. Many locations are seemingly “within reach” of the migrants, and the push factors are so loaded with hopelessness that almost anyone would be willing to risk anything to improve their conditions. There is no argument about that mass migrations are occurring and will increase in the future. The solutions to this increase are complex. This paper will examine the causes of migration and attempt to provide some reasonable solutions to mitigate the migrations with equitable outcomes that may guide immigration policy in impacted areas.

Keywords: immigration, crisis, climate, cartels

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1855 Amyloid-β Fibrils Remodeling by an Organic Molecule: Insight from All-Atomic Molecular Dynamics Simulations

Authors: Nikhil Agrawal, Adam A. Skelton

Abstract:

Alzheimer’s disease (AD) is one of the most common forms of dementia, which is caused by misfolding and aggregation of amyloid beta (Aβ) peptides into amyloid-β fibrils (Aβ fibrils). To disrupt the remodeling of Aβ fibrils, a number of candidate molecules have been proposed. To study the molecular mechanisms of Aβ fibrils remodeling we performed a series of all-atom molecular dynamics simulations, a total time of 3µs, in explicit solvent. Several previously undiscovered candidate molecule-Aβ fibrils binding modes are unraveled; one of which shows the direct conformational change of the Aβ fibril by understanding the physicochemical factors responsible for binding and subsequent remodeling of Aβ fibrils by the candidate molecule, open avenues into structure-based drug design for AD can be opened.

Keywords: alzheimer’s disease, amyloid, MD simulations, misfolded protein

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1854 Dark Gravity Confronted with Supernovae, Baryonic Oscillations and Cosmic Microwave Background Data

Authors: Frederic Henry-Couannier

Abstract:

Dark Gravity is a natural extension of general relativity in presence of a flat non dynamical background. Matter and radiation fields from its dark sector, as soon as their gravity dominates over our side fields gravity, produce a constant acceleration law of the scale factor. After a brief reminder of the Dark Gravity theory foundations, the confrontation with the main cosmological probes is carried out. We show that, amazingly, the sudden transition between the usual matter dominated decelerated expansion law a(t) ∝ t²/³ and this accelerated expansion law a(t) ∝ t² predicted by the theory should be able to fit the main cosmological probes (SN, BAO, CMB and age of the oldest stars data) but also direct H₀ measurements with two free parameters only: H₀ and the transition redshift.

Keywords: anti-gravity, negative energies, time reversal, field discontinuities, dark energy theory

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1853 Methylphenidate Use by Canadian Children and Adolescents and the Associated Adverse Reactions

Authors: Ming-Dong Wang, Abigail F. Ruby, Michelle E. Ross

Abstract:

Methylphenidate is a first-line treatment drug for attention deficit hyperactivity disorder (ADHD), a common mental health disorder in children and adolescents. Over the last several decades, the rate of children and adolescents using ADHD medication has been increasing in many countries. A recent study found that the prevalence of ADHD medication use among children aged 3-18 years increased in 13 different world regions between 2001 and 2015, where the absolute increase ranged from 0.02 to 0.26% per year. The goal of this study was to examine the use of methylphenidate in Canadian children and its associated adverse reactions. Methylphenidate use information among young Canadians aged 0-14 years was extracted from IQVIA data on prescriptions dispensed by pharmacies between April 2014 and June 2020. The adverse reaction information associated with methylphenidate use was extracted from the Canada Vigilance database for the same time period. Methylphenidate use trends were analyzed based on sex, age group (0-4 years, 5-9 years, and 10-14 years), and geographical location (province). The common classes of adverse reactions associated with methylphenidate use were sorted, and the relative risks associated with methylphenidate use as compared with two second-line amphetamine medications for ADHD were estimated. This study revealed that among Canadians aged 0-14 years, every 100 people used about 25 prescriptions (or 23,000 mg) of methylphenidate per year during the study period, and the use increased with time. Boys used almost three times more methylphenidate than girls. The amount of drug used was inversely associated with age: Canadians aged 10-14 years used nearly three times as many drugs compared to those aged 5-9 years. Seasonal methylphenidate use patterns were apparent among young Canadians, but the seasonal trends differed among the three age groups. Methylphenidate use varied from region to region, and the highest methylphenidate use was observed in Quebec, where the use of methylphenidate was at least double that of any other province. During the study period, Health Canada received 304 adverse reaction reports associated with the use of methylphenidate for Canadians aged 0-14 years. The number of adverse reaction reports received for boys was 3.5 times higher than that for girls. The three most common adverse reaction classes were psychiatric disorders, nervous system disorders and injury, poisoning procedural complications. The number one commonly reported adverse reaction for boys was aggression (11.2%), while for girls, it was a tremor (9.6%). The safety profile in terms of adverse reaction classes associated with methylphenidate use was similar to that of the selected control products. Methylphenidate is a commonly used pharmaceutical product in young Canadians, particularly in the province of Quebec. Boys used approximately three times more of this product as compared to girls. Future investigation is needed to determine what factors are associated with the observed geographic variations in Canada.

Keywords: adverse reaction risk, methylphenidate, prescription trend, use variation

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