Search results for: drug loading

Authors: Maria L. G. Lourenço, Keylla H. N. P. Pereira, Viviane Y. Hibaru, Fabiana F. Souza, Joao C. P. Ferreira, Simone B. Chiacchio, Luiz H. A. Machado

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Anasarca is generalized congenital edema that is often lethal. The condition is transmitted hereditarily and is autosomal dominant, with a racial predisposition in French Bulldogs and English Bulldogs. This study aims at reporting a case of anasarca treatment in neonates. The fetuses of a one year and six months old, primiparous English Bulldog mother were diagnosed with anasarca during an ultrasound examination performed at the 55th day of pregnancy and, therefore, an elective cesarean section was scheduled to prevent fetal dystocia. At birth, all puppies presented anasarca, and one of the six was stillborn. The newborns presented cyanosis, dyspnea, bradycardia, absent reflexes, low vitality scores (3/10), and hypothermia ( < 32ºC). The weight of the puppies at the time of birth varied between 347 and 373 grams, about 100 grams above the average weight estimated for the breed. Immediate neonatal care was applied with oxygen therapy via a mask, aminophylline (0.2 ml/100 g/PV/sublingual), and slow heating. After 10 minutes, there was a significant improvement in the neonatal parameters. The anasarca was treated with the drug furosemide, administered subcutaneously, at a dose of 0.2 mg per 100 grams of weight, every three hours. The stimulation for urination of newborns was performed every 30 minutes, and weight loss was monitored every 30 minutes. Five grams of potassium chloride were administered orally for every 30 grams of weight loss to counterbalance the loss of potassium caused by the diuretic medication. After 15 hours, the neonates reached the ideal weight for the breed, around 209 to 230 grams. In total, four neonates received five doses of furosemide, while one received six doses. The puppies are currently ten months old, healthy and neutered. Anasarca should not be ignored and is considered potentially lethal and an indication for euthanasia in all cases. Early intervention is of utmost importance for the survival of these patients.

Keywords: Walrus syndrome, congenital edema, water puppy syndrome, puppies

Procedia PDF Downloads 182

Authors: M. Khaing, A. V. Tkacheva

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The work is devoted to solving the problem of temperature stresses, caused by the heating point of the round plate. The plate is made of elastoplastic material, so the Prandtl-Reis model is used. A piecewise-linear condition of the Ishlinsky-Ivlev flow is taken as the loading surface, in which the yield stress depends on the temperature. Piecewise-linear conditions (Treska or Ishlinsky-Ivlev), in contrast to the Mises condition, make it possible to obtain solutions of the equilibrium equation in an analytical form. In the problem under consideration, using the conditions of Tresca, it is impossible to obtain a solution. This is due to the fact that the equation of equilibrium ceases to be satisfied when the two Tresca conditions are fulfilled at once. Using the conditions of plastic flow Ishlinsky-Ivlev allows one to solve the problem. At the same time, there are also no solutions on the edge of the Ishlinsky-Ivlev hexagon in the plane-stressed state. Therefore, the authors of the article propose to jump from the edge to the edge of the mine edge, which gives an opportunity to obtain an analytical solution. At the same time, there is also no solution on the edge of the Ishlinsky-Ivlev hexagon in a plane stressed state; therefore, in this paper, the authors of the article propose to jump from the side to the side of the mine edge, which gives an opportunity to receive an analytical solution. The paper compares solutions of the problem of plate thermal deformation. One of the solutions was obtained under the condition that the elastic moduli (Young's modulus, Poisson's ratio) which depend on temperature. The yield point is assumed to be parabolically temperature dependent. The main results of the comparisons are that the region of irreversible deformation is larger in the calculations obtained for solving the problem with constant elastic moduli. There is no repeated plastic flow in the solution of the problem with elastic moduli depending on temperature. The absolute value of the irreversible deformations is higher for the solution of the problem in which the elastic moduli are constant; there are also insignificant differences in the distribution of the residual stresses.

Keywords: temperature stresses, elasticity, plasticity, Ishlinsky-Ivlev condition, plate, annular heating, elastic moduli

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Authors: Mario J. Meco-Gutierrez, Francisco Perez-Hidalgo, Juan R. Heredia-Larrubia, Antonio Ruiz-Gonzalez, Francisco Vargas-Merino

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More and more applications power inverters connected to transformers, for example, the connection facilities to the power grid renewable generation. It is well known that the quality of signal power inverters it is not a pure sine. The harmonic content produced negative effects, one of which is the heating of electrical machines and therefore, affects the life of the machines. The decrease of life of transformers can be calculated by Arrhenius or Montsinger equation. Analyzing this expression any (long-term) decrease of a transformer temperature for 6º C - 7º C means doubles its life-expectancy. Methodologies: This work presents the technique of pulse width modulation (PWM) with an injection of harmonic and triangular frequency carrier modulated in frequency. This technique is used to improve the quality of the output voltage signal of the power inverters controlled PWM. The proposed technique increases in the fundamental term and a significant reduction in low order harmonics with the same commutations per time that control sine PWM. To achieve this, the modulating wave is compared to a triangular carrier with variable frequency over the period of the modulator. Therefore, it is, advantageous for the modulating signal to have a large amount of sinusoidal “information” in the areas of greater sampling. A triangular signal with a frequency that varies over the modulator’s period is used as a carrier, for obtaining more samples in the area with the greatest slope. A power inverter controlled by PWM proposed technique is connected to a transformer. Results: In order to verify the derived thermal parameters under different operation conditions, another ambient and loading scenario is involved for a further verification, which was sampled from the same power transformer. Temperatures of different parts of the transformer will be exposed for each PWM control technique analyzed. An assessment of the temperature be done with different techniques PWM control and hence the life of the transformer is calculated for each technique. Conclusion: This paper analyzes such as transformer heating produced by this technique and compared with other forms of PWM control. In it can be seen as a reduction the harmonic content produces less heat transformer and therefore, an increase in the life of the transformer.

Keywords: heating, power-inverter, PWM, transformer

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Authors: Silvia Platania, Martina Morando, Giuseppe Santisi

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Introduction: In the last thirty years, there is constant talk of sustainable consumption and a "transition" of consumer lifestyles towards greater awareness of consumer choices (United Nation, 1992). The 2019 coronavirus (COVID-19) epidemic that has hit the world population since 2020 has had significant consequences in all areas of people's lives; individuals have been forced to change their behaviors, to redefine their owngoals, priorities, practices, and lifestyles, to rebuild themselves in the new situation dictated by the pandemic. Method(Participants and procedure ): The data were collected through an online survey; moreover, we used convenience sampling from the general population. The participants were 669 Italians consumers (Female= 514, 76.8%; Male=155, 23.2%) that choice sustainability brands, aged between 18 and 65 years (Mₐ𝓰ₑ = 35.45; Standard Deviation, SD = 9.51).(Measure ): The following measures were used: The Muncy–Vitell Consumer Ethics Scale; Attitude Toward Business Scale; Perceived Consumer Effectiveness Scale; Consumers Perception on Sustainable Brand Attitudes. Results: Preliminary analyses were conducted to test our model. Pearson's bivariate correlation between variables shows that all variables of our model correlate significantly and positively, PCE with CPSBA (r = .56, p <.001). Furthermore, a CFA, according to Harman's single-factor test, was used to diagnose the extent to which common-method variance was a problem. A comparison between the hypothesised model and a model with one factor (with all items loading on a unique factor) revealed that the former provided a better fit for the data in all the CFA fit measures [χ² [6, n = 669] = 7.228, p = 0.024, χ² / df = 1.20, RMSEA = 0.07 (CI = 0.051-0.067), CFI = 0.95, GFI = 0.95, SRMR = 0.04, AIC = 66.501; BIC = 132,150). Next, amulti mediation was conducted to test our hypotheses. The results show that there is a direct effect of PCE on ethical consumption behavior (β = .38) and on ATB (β = .23); furthermore, there is a direct effect on the CPSBA outcome (β = .34). In addition, there is a mediating effect by ATB (C.I. =. 022-.119, 95% interval confidence) and by CES (C.I. =. 136-.328, 95% interval confidence). Conclusion: The spread of the COVID-19 pandemic has affected consumer consumption styles and has led to an increase in online shopping and purchases of sustainable products. Several theoretical and practical considerations emerge from the results of the study.

Keywords: decision making, sustainability, pandemic, multimediation model

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Authors: Maryam S. Ghoraishi, John E. Hawk, Thomas Thundat

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Understanding liquid properties in small scale has become important in recent decades as immerging new microelectromechanical systems (MEMS) devices have been widely used for micro pumps, drug delivery, and many other laboratory-on-microchips analysis. Often in microfluidic devices, fluids are transported electrokinetically. Therefore, extensive knowledge of fluid flow, heat transport, electrokinetics and electrochemistry are key to successful lab on a chip design. Among different microfluidic devices, recently developed hollow channel cantilever offers an ideal platform to study different fluid properties simultaneously without drastic decrease in quality factor which normally occurs when traditional cantilevers operate in the liquid phase. Using hollow channel cantilever, we monitor changes in density and viscosity of liquid while simultaneously investigating dielectric properties of alcohol water binary mixtures. Considerable research has been conducted on alcohol-water mixtures since such a mixture is a typical prototype for biomolecules, Micelle formation, and structural stability of proteins (to name a few). Here we show that hollow channel cantilever can be employed to investigate dielectric properties of ethanol/water mixtures in different concentrations. We study dynamic amplitude shifts of hollow channel cantilever oscillation at different concentrations of ethanol/water for different voltages. Our results show how interactions between solute and solvent, and possibly cluster formation, could change dielectric properties and dipole reorientation of the mixture, as well as the resulting force on the hollow cantilever. For comparison, we also examine higher conductivity ionic mixtures of sodium sulfate solution under the same conditions as low conductivity ethanol/water mixtures. We will show the results from systematic investigation of solvent effects on dielectric properties of the binary mixture. We will also address the question of resolution limits in dielectric study of analyte molecules imposed by solvent concentrations.

Keywords: dielectric constant, cantilever sensors, ethanol water mixtures, low frequency

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Authors: Prerna Kalra, Surender Singh

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Cisplatin is the most common chemotherapeutic agent used in different solid tumors, but its main limiting factor is dose-dependent nephrotoxicity by generating reactive oxygen species, by stimulating inflammatory and apoptotic pathways. Additional adjuvant therapies to decrease the toxicity of this chemotherapeutic drug are essential. This study was designed to evaluate the protective role of Emblica officinalis Geartn (Indian gooseberry) against cisplatin induced nephrotoxicity. Emblica officinalis was orally administered to Wistar rats (n=6) for 10 days in 50, 100 and 200mg/kg body weight. On day 7, 8mg/kg of cisplatin was administered intra-peritoneally to rats in all groups. Serum creatinine, blood urea nitrogen and antioxidant levels were measured on day10. The renal damage was evaluated by histopathological and transmission electron microscopy. We found that 200mg/kg dose of Emblica officinalis significantly inhibited the elevation of biochemical parameters i.e. serum creatinine, blood urea nitrogen, oxidant stress marker (malondialdehyde) and increased the reduced levels of antioxidant marker (endogenous glutathione and superoxide dismutase). Cisplatin treated rats have shown acute tubular necrosis and infiltration of inflammatory cells in rat kidney which was reversed after treating the animals with Emblica officinalis in the treatment group. In ultrastructural changes cisplatin treated group showed the damaged mitochondria (M) with dissolved cristae and large number of lysosomes (L) and vacuole (V) formation in tubular epithelial cells. EOE administered group showed visible cristae formation and sign of autophagy vacuoles at a dose of 200mg/kg. Further in-silico studies revealed that ellagic acid is responsible for its nephroprotective effect. The above findings conclude that the Emblica officinalis may be used as an adjuvant therapy in cisplatin induced nephrotoxicity.

Keywords: antioxidant, cisplatin, Emblica officinalis, in silico, nephrotoxicity

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Authors: Zia R. Tahir, P. Mandal

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This paper presents the details of a numerical study of buckling and post buckling behaviour of laminated carbon fiber reinforced plastic (CFRP) thin-walled cylindrical shell under axial compression using asymmetric meshing technique (AMT) by ABAQUS. AMT is considered to be a new perturbation method to introduce disturbance without changing geometry, boundary conditions or loading conditions. Asymmetric meshing affects both predicted buckling load and buckling mode shapes. Cylindrical shell having lay-up orientation [0°/+45°/-45°/0°] with radius to thickness ratio (R/t) equal to 265 and length to radius ratio (L/R) equal to 1.5 is analysed numerically. A series of numerical simulations (experiments) are carried out with symmetric and asymmetric meshing to study the effect of asymmetric meshing on predicted buckling behaviour. Asymmetric meshing technique is employed in both axial direction and circumferential direction separately using two different methods, first by changing the shell element size and varying the total number elements, and second by varying the shell element size and keeping total number of elements constant. The results of linear analysis (Eigenvalue analysis) and non-linear analysis (Riks analysis) using symmetric meshing agree well with analytical results. The results of numerical analysis are presented in form of non-dimensional load factor, which is the ratio of buckling load using asymmetric meshing technique to buckling load using symmetric meshing technique. Using AMT, load factor has about 2% variation for linear eigenvalue analysis and about 2% variation for non-linear Riks analysis. The behaviour of load end-shortening curve for pre-buckling is same for both symmetric and asymmetric meshing but for asymmetric meshing curve behaviour in post-buckling becomes extraordinarily complex. The major conclusions are: different methods of AMT have small influence on predicted buckling load and significant influence on load displacement curve behaviour in post buckling; AMT in axial direction and AMT in circumferential direction have different influence on buckling load and load displacement curve in post-buckling.

Keywords: CFRP composite cylindrical shell, asymmetric meshing technique, primary buckling, secondary buckling, linear eigenvalue analysis, non-linear riks analysis

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Authors: Ariba Siddiqui, Amber Khan

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The need for bio-implantable devices in the field of medical sciences has been increasing day by day; however, the charging of these devices is a major issue. Batteries, a very common method of powering the implants, have a limited lifetime and bulky nature. Therefore, as a replacement of batteries, acoustic power transfer (APT) technology is being accepted as the most suitable technique to wirelessly power the medical implants in the present scenario. The basic model of APT consists of piezoelectric transducers that work on the principle of converse piezoelectric effect at the transmitting end and direct piezoelectric effect at the receiving end. This paper provides mechanistic insight into the parameters affecting the design and efficient working of acoustic power transfer systems. The optimum design considerations have been presented that will help to compress the size of the device and augment the intensity of the pressure wave. A COMSOL model of the PZT (Lead Zirconate Titanate) transducer was developed. The model was simulated and analyzed on a frequency spectrum. The simulation results displayed that the efficiency of these devices is strongly dependent on the frequency of operation, and a wrong choice of the operating frequency leads to the high absorption of acoustic field inside the tissue (medium), poor power strength, and heavy transducers, which in effect influence the overall configuration of the acoustic systems. Considering all the tradeoffs, the simulations were performed again by determining an optimum frequency (900 kHz) that resulted in the reduction of the transducer's thickness to 1.96 mm and augmented the power strength with an intensity of 432 W/m². Thus, the results obtained after the second simulation contribute to lesser attenuation, lightweight systems, high power intensity, and also comply with safety limits provided by the U.S Food and Drug Administration (FDA). It was also found that the chosen operating frequency enhances the directivity of the acoustic wave at the receiver side.

Keywords: acoustic power, bio-implantable, COMSOL, Lead Zirconate Titanate, piezoelectric, transducer

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Authors: Debabrata Biswas

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The current trend in the development of antibiotic resistance by multiple bacterial pathogens has resulted in a troubling loss of effective antibiotic options for human. The emergence of multi-drug-resistant pathogens has necessitated higher dosages and combinations of multiple antibiotics, further exacerbating the problem of antibiotic resistance. Zoonotic bacterial pathogens, such as Salmonella, Campylobacter, Shiga toxin-producing Escherichia coli (such as enterohaemorrhagic E. coli or EHEC), and Listeria are the most common and predominant foodborne enteric infectious agents. It was observed that these pathogens gained/developed their ability to survive in the presence of antibiotics either in farm animal gut or farm environment and researchers believe that therapeutic and sub-therapeutic antibiotic use in farm animal production might play an important role in it. The mechanism of action of antimicrobial components used in farm animal production in genomic interplay in the gut and farm environment, has not been fully characterized. Even the risk of promoting the exchange of mobile genetic elements between microbes specifically pathogens needs to be evaluated in depth, to ensure sustainable farm animal production, safety of our food and to mitigate/limit the enteric infection with multiple antibiotic resistant bacterial pathogens. Due to the consumer’s demand and considering the current emerging situation, many countries are in process to withdraw antibiotic use in farm animal production. Before withdrawing use of the sub-therapeutic antibiotic or restricting the use of therapeutic antibiotics in farm animal production, it is essential to find alternative natural antimicrobials for promoting the growth of farm animal and/or treating animal diseases. Further, it is also necessary to consider whether that compound(s) has the potential to trigger the acquisition or loss of genetic materials in zoonotic and any other bacterial pathogens. Development of alternative therapeutic and sub-therapeutic antimicrobials for farm animal production and food processing and preservation and their effective implementation for sustainable strategies for farm animal production as well as the possible risk for horizontal gene transfer in major enteric pathogens will be focus in the study.

Keywords: food safety, natural antimicrobial, sustainable farming, antibiotic resistance

Procedia PDF Downloads 270

Authors: Eslam Mohammed Abdelkader, Mohamed Marzouk, Tarek Zayed

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Infrastructure systems are crucial to every aspect of life on Earth. Existing Infrastructure is subjected to degradation while the demands are growing for a better infrastructure system in response to the high standards of safety, health, population growth, and environmental protection. Bridges play a crucial role in urban transportation networks. Moreover, they are subjected to high level of deterioration because of the variable traffic loading, extreme weather conditions, cycles of freeze and thaw, etc. The development of Bridge Management Systems (BMSs) has become a fundamental imperative nowadays especially in the large transportation networks due to the huge variance between the need for maintenance actions, and the available funds to perform such actions. Deterioration models represent a very important aspect for the effective use of BMSs. This paper presents a probabilistic time-based model that is capable of predicting the condition ratings of the concrete bridge decks along its service life. The deterioration process of the concrete bridge decks is modeled using semi-Markov process. One of the main challenges of the Markov Chain Decision Process (MCDP) is the construction of the transition probability matrix. Yet, the proposed model overcomes this issue by modeling the sojourn times based on some probability density functions. The sojourn times of each condition state are fitted to probability density functions based on some goodness of fit tests such as Kolmogorov-Smirnov test, Anderson Darling, and chi-squared test. The parameters of the probability density functions are obtained using maximum likelihood estimation (MLE). The condition ratings obtained from the Ministry of Transportation in Quebec (MTQ) are utilized as a database to construct the deterioration model. Finally, a comparison is conducted between the Markov Chain and semi-Markov chain to select the most feasible prediction model.

Keywords: bridge management system, bridge decks, deterioration model, Semi-Markov chain, sojourn times, maximum likelihood estimation

Procedia PDF Downloads 211

Authors: Victor U. Odoemelam, Ihemdirim C. Unamba-Opara, Martins C. Anyanwuocha

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Antibiotics used as growth promoters in animal feeds have been criticized and banned in many nations due to possible development of both drug resistance, cross resistance and multiple resistances by consumers. Numerous additives are now being used or proposed as alternatives. A study to compare the effects of Ocimum gratissimum (Scent leaf) and antibiotic growth promoter (Oxytetracycline HCl) on growth performance and intestinal morphology of starter broiler birds was conducted using ninety six (96) days old broiler birds. The birds were randomly assigned to four treatments with each treatment comprising 24 birds replicated three times with 8 birds per replicate in a completely randomized design experiment. Four diets (T1 control diet without Oxytetracycline HCl and Ocimum gratissimum; T2 had Oxytetracycline HCl; T3 had 1% Ocimum gratissimum; T4 had 1.5% Ocimum gratissimum) were formulated and offered ad libitum to the respective birds. Data was collected on feed intake, body weight gain and feed conversion ratio (FCR) also Jejenal sections of the intestine were collected for examination of Villi length and Crypt depth at the end of starter phase. Results show that there were no significant difference (P>0.05) observed in feed intake and final body weight. However, feed conversion ratio (FCR) and daily weight gain significantly differed (P<0.05). T1, T2, and T4 were similar, however T2 differed (P<0.05) from T3. FCR followed the same pattern. Dietary treatment significantly (P<0.05) affected Villi length, Crypt depth and Villi length/crypt depth ratio. Birds fed OG containing diets, had significantly higher (P<0.05) villi length/crypt depth ratio. However, this did not translate to a significantly higher body weight gain or feed conversion ratio. It can be concluded that O. gratissimum can replace antibiotic growth promoter (Oxytetracycline HCl) since their effect on performance were similar.

Keywords: antibiotics, body weight, feed additives, intestinal morphology, phytogenics

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Authors: Rasha Ahmadi

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In December 2019, a coronavirus, currently identified as SARS-CoV-2, produced a series of acute atypical respiratory illnesses in Wuhan, Hubei Province, China. The sickness induced by this virus was named COVID-19. The virus is transmittable between humans and has caused pandemics worldwide. The number of death tolls continues to climb and a huge number of countries have been obliged to perform social isolation and lockdown. Lack of focused therapy continues to be a problem. Epidemiological research showed that senior patients were more susceptible to severe diseases, whereas children tend to have milder symptoms. In this study, we focus on other possible side effects of COVID-19 and more detailed treatment strategies. Using bioinformatics analysis, we first isolated the gene expression profile of patients with severe COVID-19 from the GEO database. Patients' blood samples were used in the GSE183071 dataset. We then categorized the genes with high and low expression. In the next step, we uploaded the genes separately to the Enrichr database and evaluated our data for signs and symptoms as well as related medication regimens. The results showed that 138 genes with high expression and 108 genes with low expression were observed differentially in the severe COVID-19 VS control group. Symptoms and diseases such as embolism and thrombosis of the abdominal aorta, ankylosing spondylitis, suicidal ideation or attempt, regional enteritis were observed in genes with high expression and in genes with low expression of acute and subacute forms of ischemic heart, CNS infection and poliomyelitis, synovitis and tenosynovitis. Following the detection of diseases and possible signs and symptoms, Carmustine, Bithionol, Leflunomide were evaluated more significantly for high-expression genes and Chlorambucil, Ifosfamide, Hydroxyurea, Bisphenol for low-expression genes. In general, examining the different and invisible aspects of COVID-19 and identifying possible treatments can help us significantly in the emergency and hospitalization of patients.

Keywords: phenotypes, drug regimens, gene expression profiles, bioinformatics analysis, severe COVID-19

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Authors: Mohit Wadhawan, Sushma Rathaur

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Lymphatic filariasis, also called elephantiasis is a tropical disease afflicting over 120 million people in 81 countries worldwide. Existing anti filarial drugs are effective against the larval stages of filarial parasites which call for an urgent need of drugs which are macrofilaricidal. Identification of molecular targets crucial for survival of filarial parasites is a prerequisite for drug designing. Prolyl oligopeptidase (POP) is one such crucial enzyme involved in the maturation and degradation of neuropeptides and peptide hormones. We have identified this peptidase in the bovine filarial parasite, Setaria cervi. Effect of inhibition of POP on the proteome profile of filarial parasite has been discussed in this study. Filarial parasites were exposed to Z-pro-prolinal (ZPP), a specific POP inhibitor for 8 h and the motility and viability of the parasites was observed. It significantly reduced the motility and viability of the parasites. To study the proteome profile, the cytosolic, endoplasmic reticulum (ER) and mitochondrial extracts of the adult female parasites were subjected to 2-dimensional electrophoresis. As analyzed by the PD-Quest software, the ZPP caused the alteration in the different subcellular proteins, and the significantly altered proteins were identified using MALDI-MS/MS spectrometry. The major proteins identified were found to play important role in diverse biological functions like signaling, redox regulation, energy metabolism, stress response, and cytoskeleton formation. Moreover, we found upregulation in the calcium binding proteins such as calreticulin, calponin, and calpain-6 suggesting that POP inhibition regulates calcium release. This relates to earlier reports that POP plays non-catalytic role in inositol 1,4,5-trisphosphate (IP3) signaling inducing release of calcium from ER. Taken together, the data demonstrated that inhibition of prolyl oligopeptidase alter the overall proteome signifying its role in survival of the filarial parasites. Thus this study provides a basis for the use of POP as a chemotherapeutic target for the treatment of lymphatic filariasis.

Keywords: lymphatic filariasis, setaria cervi, prolyl oligopeptidase, proteomics

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Authors: Ádám Vass, István Bakos, Irina Borbáth, Zoltán Pászti, István Sajó, András Tompos

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Important requirements for the anode side electrocatalysts of polymer electrolyte membrane (PEM) fuel cells are CO-tolerance, stability and corrosion resistance. Carbon is still the most common material for electrocatalyst supports due to its low cost, high electrical conductivity and high surface area, which can ensure good dispersion of the Pt. However, carbon becomes degraded at higher potentials and it causes problem during application. Therefore it is important to explore alternative materials with improved stability. Molybdenum-oxide can improve the CO-tolerance of the Pt/C catalysts, but it is prone to leach in acidic electrolyte. The Mo was stabilized by isovalent substitution of molybdenum into the rutile phase titanium-dioxide lattice, achieved by a modified multistep sol-gel synthesis method optimized for preparation of Ti0.7Mo.3O2-C composite. High degree of Mo incorporation into the rutile lattice was developed. The conductivity and corrosion resistance across the anticipated potential/pH window was ensured by mixed oxide – activated carbon composite. Platinum loading was carried out using NaBH4 and ethylene glycol; platinum content was 40 wt%. The electrocatalyst was characterized by both material investigating methods (i.e. XRD, TEM, EDS, XPS techniques) and electrochemical methods (cyclic-voltammetry, COads stripping voltammetry, hydrogen oxidation reaction on rotating disc electrode). The electrochemical activity of the sample was compared to commercial 40 wt% Pt/C (Quintech) and PtRu/C (Quintech, Pt= 20 wt%, Ru= 10 wt%) references. Enhanced CO tolerance of the electrocatalyst prepared using the Ti0.7Mo.3O2-C composite material was evidenced by the appearance of a CO-oxidation related 'pre-peak' and by the pronounced shift of the maximum of the main CO oxidation peak towards less positive potential compared to Pt/C. Fuel cell polarization measurements were also carried out using Bio-Logic and Paxitech FCT-150S test device. All details on the design, preparation, characterization and testing by both electrochemical measurements and fuel cell test device of electrocatalyst supported on Ti0.7Mo.3O2-C composite material will be presented and discussed.

Keywords: anode electrocatalyst, composite material, CO-tolerance, TiMoOx

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Authors: Paul V. Thomas, Mostafa S. A. Elsayed, Denis Walch

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Airframe structural optimization at different design stages results in new mass and stiffness distributions which modify the critical design loads envelop. Determination of aircraft critical loads is an extensive analysis procedure which involves simulating the aircraft at thousands of load cases as defined in the certification requirements. It is computationally prohibitive to use a Global Finite Element Model (GFEM) for the load analysis, hence reduced order structural models are required which closely represent the dynamic characteristics of the GFEM. This paper presents the implementation of Component Mode Synthesis (CMS) method for the generation of high fidelity Reduced Order Model (ROM) of complex airframes. Here, sub-structuring technique is used to divide the complex higher order airframe dynamical system into a set of subsystems. Each subsystem is reduced to fewer degrees of freedom using matrix projection onto a carefully chosen reduced order basis subspace. The reduced structural matrices are assembled for all the subsystems through interface coupling and the dynamic response of the total system is solved. The CMS method is employed to develop the ROM of a Bombardier Aerospace business jet which is coupled with an aerodynamic model for dynamic aeroelasticity loads analysis under gust turbulence. Another set of dynamic aeroelastic loads is also generated employing a stick model of the same aircraft. Stick model is the reduced order modelling methodology commonly used in the aerospace industry based on stiffness generation by unitary loading application. The extracted aeroelastic loads from both models are compared against those generated employing the GFEM. Critical loads Modal participation factors and modal characteristics of the different ROMs are investigated and compared against those of the GFEM. Results obtained show that the ROM generated using Craig Bampton CMS reduction process has a superior dynamic characteristics compared to the stick model.

Keywords: component mode synthesis, craig bampton reduction method, dynamic aeroelasticity analysis, model order reduction

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Authors: Yimeng Zhang

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Major depressive disorder (MDD) is a prevalent mental health condition with a substantial economic impact and limited treatment options. Acupuncture has gained attention as a promising non-pharmacological intervention for alleviating depressive symptoms. However, its mechanisms and clinical effectiveness remain incompletely understood. This meta-analysis aims to (1) synthesize existing evidence on the mechanisms and clinical effectiveness of acupuncture for depression and (2) compare these findings with pharmacological interventions, providing insights for future research. Evidence from animal models and clinical studies indicates that acupuncture may enhance hippocampal and network neuroplasticity and reduce brain inflammation, potentially alleviating depressive disorders. Clinical studies suggest that acupuncture can effectively relieve primary depression, particularly in milder cases, and is beneficial in managing post-stroke depression, pain-related depression, and postpartum depression, both as a standalone and adjunctive treatment. Notably, combining acupuncture with antidepressant pharmacotherapy appears to enhance treatment outcomes and reduce medication side effects, addressing a critical issue in conventional drug therapy's high dropout rates. This meta-analysis, encompassing 12 studies and 710 participants, draws data from eight digital databases (PubMed, EMBASE, Web of Science, EBSCOhost, CNKI, CBM, Wangfang, and CQVIP) covering the period from 2012 to 2022. Utilizing Stata software 15.0, the meta-analysis employed random-effects and fixed-effects models to assess the distribution of depression in Traditional Chinese Medicine (TCM). The results underscore the substantial evidence supporting acupuncture's beneficial effects on depression. However, the small sample sizes of many clinical trials raise concerns about the generalizability of the findings, indicating a need for further research to validate these outcomes and optimize acupuncture's role in treating depression.

Keywords: Chinese medicine, acupuncture, depression, meta-analysis

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Authors: Levicatus Mugenyi, Joaniter Nankabirwa, Emmanuel Arinaitwe, John Rek, Niel Hens, Moses Kamya, Grant Dorsey

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Background: Indoor residual spraying (IRS) reduces vector densities and malaria transmission, however, the most effective spraying intervals for IRS have not been well established. We aim to estimate the optimal timing interval for IRS using a modeling approach. Methods: We use a generalized additive model to estimate the optimal timing interval for IRS using the predicted malaria incidence. The model is applied to post IRS cohort clinical data from children aged 0.5–10 years in selected households in Tororo, historically a high malaria transmission setting in Uganda. Six rounds of IRS were implemented in Tororo during the study period (3 rounds with bendiocarb: December 2014 to December 2015, and 3 rounds with actellic: June 2016 to July 2018). Results: Monthly incidence of malaria from October 2014 to February 2019 decreased from 3.25 to 0.0 per person-years in the children under 5 years, and 1.57 to 0.0 for 5-10 year-olds. The optimal time interval for IRS differed between bendiocarb and actellic and by IRS round. It was estimated to be 17 and 40 weeks after the first round of bendiocarb and actellic, respectively. After the third round of actellic, 36 weeks was estimated to be optimal. However, we could not estimate from the data the optimal time after the second and third rounds of bendiocarb and after the second round of actellic. Conclusion: We conclude that to sustain the effect of IRS in a high-medium transmission setting, the second rounds of bendiocarb need to be applied roughly 17 weeks and actellic 40 weeks after the first round, and the timing differs for subsequent rounds. The amount of rainfall did not influence the trend in malaria incidence after IRS, as well as the IRS timing intervals. Our results suggest that shorter intervals for the IRS application can be more effective compared to the current practice, which is about 24 weeks for bendiocarb and 48 weeks for actellic. However, when considering our findings, one should account for the cost and drug resistance associated with IRS. We also recommend that the timing and incidence should be monitored in the future to improve these estimates.

Keywords: incidence, indoor residual spraying, generalized additive model, malaria

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Authors: Alexandru Grigorescu, Alexandra Protesanu

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Background: Approximately 34-67 percent of cancer patients experience an episode of uncontrolled pain during the course of their disease, depending on the stage. The aim is to provide evidence-based data for pain prevalence, diagnosis and treatment recommendations on an integrative model of medical oncology and palliative care for patients with cancer diagnostic in a day hospital. Patients and method: Consultation registers and electronic records of 166 Patients (Pts) were studied from April 2022 to March 2023. Pts with pain syndrome were selected. The pain was objectified by the visual pain scale. To elucidate the causes of the pain, investigations were carried out: bone scintigraphy, CT scan, and PET-CT. The analgesic treatments were represented by weak and strong morphine, radiotherapy, and bisphosphonates. Result: During the mentioned period, 166 oncological patients (74 women and 92 men) were treated in the oncology day hospitalization service. There were 1,500 consultations, 40 of which were only for pain. The neoplastic locations were: gynecological, malignant melanoma, breast, gastric, bronchopulmonary, colorectal, liver, pancreatic, bladder, and kidney. 70 Pts presented pain syndrome. The causes of the pain were represented by bone metastases, compressive tumors, and post-surgical status. Drug treatment: Tramadol 47 Pts, of which 10 switched to a major opioid (Oxycodonum, Morphine sulfate), 20 Pts were treated with Oxycodonum as the first intention. In 5 patients ry to rotated morphine, 20 Pts received palliative radiotherapy, 10 Pts were treated with bisphosphonates. 2 Pts required neurosurgery consultation for an antalgic intervention. 5 Pts had important adverse reactions to morphine. All patients and their families were advised by a medical oncologist and psychologist for a lifestyle change. Conclusions: The prevalence of pain was similar to that described in the literature. In most cases, the pain could be managed in the day hospital. Weak and strong morphine represented the main pain therapy. Palliative radiotherapy was the second most effective therapy. Treatment with bisphosphonates was useful. Surgical interventions were rarely indicated. Discussions with patients and their families regarding the lifestyle change were important.

Keywords: cancer pain, opioids, medical oncology, palliative care

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Authors: Chow Jeng Hei, Pavel Tkalich, Low Kai Sheng Bryan

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Due to the growing demand for sustainability in the maritime industry, there has been a significant increase in focus on alternative fuels such as biofuels, liquefied natural gas (LNG), hydrogen, methanol and ammonia to reduce the carbon footprint of vessels. Alternative fuels offer efficient transportability and significantly reduce carbon dioxide emissions, a critical factor in combating global warming. In an era where the world is determined to tackle climate change, the utilization of methanol is projected to witness a consistent rise in demand, even during downturns in the oil and gas industry. Since 2022, there has been an increase in methanol loading and discharging operations for industrial use in Singapore. These operations were conducted across various storage tank terminals at Jurong Island of varying capacities, which are also used to store alternative fuels for bunkering requirements. The key objective of this research is to support the green shipping industries in the transformation to new fuels such as methanol and ammonia, especially in evolving the capability to inform risk assessment and management of spills. In the unlikely event of accidental spills, a highly reliable forecasting system must be in place to provide mitigation measures and ahead planning. The outcomes of this research would lead to an enhanced metocean prediction capability and, together with advanced sensing, will continuously build up a robust digital twin of the bunkering operating environment. Outputs from the developments will contribute to management strategies for alternative marine fuel spills, including best practices, safety challenges and crisis management. The outputs can also benefit key port operators and the various bunkering, petrochemicals, shipping, protection and indemnity, and emergency response sectors. The forecasted datasets provide a forecast of the expected atmosphere and hydrodynamic conditions prior to bunkering exercises, enabling a better understanding of the metocean conditions ahead and allowing for more refined spill incident management planning

Keywords: clean fuels, hydrodynamics, coastal engineering, impact assessments

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Authors: Samar Saadeldin Abdelmotalab Omer, Ikram Mohammed Eltayeb Elsiddig, Amna Beshir Medani Ahmed, Saad Mohammed Hussein Ayoub

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Many herbal medicinal products are considered as potential hypocholesterolemic agents with encouraging safety profiles, however, only a limited amount of clinical research exists to support their efficacy. The present study was designed to compare the antihypercholesterolaemic and antioxidant activities of the crude ethanolic extracts of Citrus reticulata peel, Zingiber officinale rhizome, and Sesamum indicum seeds. Forty-five rats were used throughout the experiment, which were divided into nine groups, five rats in each as follows; normal control group (normal rats fed with standard normal diet), rats fed hypercholesterolemic diet consisting of 1% cholesterol and 10% saturated animal fat, which were further divided into eight groups; hypercholesterolemic control group (rats only fed hypercholesterolemic diet), groups 3,4,5,6,7, and 8 were given Citrus reticulata, Zingiber officinale, and Sesamum indicum ethanolic extracts at doses of (250mg/kg and 500mg/kg, respectively) orally; and group 9 rats were given atorvastatin (0.18mg/kg) orally as a reference antihypercholesterolaemic drug. Blood samples were obtained four weeks following treatment from the retro-orbital venous plexus after fasting overnight from all groups and the lipid profile (serum total cholesterol (TC), high-density-lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglycerides levels) was measured and the risk ratio (TC/HDL-C) was assessed. The antioxidant activity of the three plant extracts was determined using DPPH free-radical assay. Results of in vivo and in vitro antihypercholesterolaemic and antioxidant assay, respectively, revealed that the three extracts possess comparable antioxidant and anti-hypercholesterolaemic activities.

Keywords: anti hypercholesterolemic effects, antioxidant activity, HDL, LDL, TC, TGs, citrus reticulata, sesamum indicum, zingiber officinale

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Authors: Kinga Mylkie, Pawel Nowak, Marta Z. Borowska

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The most important proteins in human serum responsible for drug binding are human serum albumin (HSA) and α1-acid glycoprotein (AGP). The AGP molecule is a glycoconjugate containing a single polypeptide chain composed of 183 amino acids (the core of the protein), and five glycan branched chains (sugar part) covalently linked by an N-glycosidic bond with aspartyl residues (Asp(N) -15, -38, -54, -75, - 85) of polypeptide chain. This protein plays an important role in binding alkaline drugs, a large group of drugs used in psychiatry, some acid drugs (e.g., coumarin anticoagulants), and neutral drugs (steroid hormones). The main goal of the research was to obtain magnetic nanoparticles coated with biopolymers in a chemically modified form, which will have highly reactive functional groups able to effectively immobilize the glycoprotein (acid α1-glycoprotein) without losing the ability to bind active substances. The first phase of the project involved the chemical modification of biopolymer starch. Modification of starch was carried out by methods of organic synthesis, leading to the preparation of a polymer enriched on its surface with aldehyde groups, which in the next step was coupled with 3-aminophenylboronic acid. Magnetite nanoparticles coated with starch were prepared by in situ co-precipitation and then oxidized with a 1 M sodium periodate solution to form a dialdehyde starch coating. Afterward, the reaction between the magnetite nanoparticles coated with dialdehyde starch and 3-aminophenylboronic acid was carried out. The obtained materials consist of a magnetite core surrounded by a layer of modified polymer, which contains on its surface dihydroxyboryl groups of boronic acids which are capable of binding glycoproteins. Magnetic nanoparticles obtained as carriers for plasma protein immobilization were fully characterized by ATR-FTIR, TEM, SEM, and DLS. The glycoprotein was immobilized on the obtained nanoparticles. The amount of mobilized protein was determined by the Bradford method.

Keywords: glycoproteins, immobilization, magnetic nanoparticles, polysaccharides

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Authors: M. Miljkovic, A. Urakpo, M. Simic-Koumoutsaris

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Benefit-risk assessment (BRA) is a valuable tool that takes place in multiple stages during a medicine's lifecycle, and this assessment can be conducted in a variety of ways. The aim was to summarize current BRA methods used during approval decisions and in post-approval settings and to see possible future directions. Relevant reviews, recommendations, and guidelines published in medical literature and through regulatory agencies over the past five years have been examined. BRA implies the review of two dimensions: the dimension of benefits (determined mainly by the therapeutic efficacy) and the dimension of risks (comprises the safety profile of a drug). Regulators, industry, and academia have developed various approaches, ranging from descriptive textual (qualitative) to decision-analytic (quantitative) models, to facilitate the BRA of medicines during the product lifecycle (from Phase I trials, to authorization procedure, post-marketing surveillance and health technology assessment for inclusion in public formularies). These approaches can be classified into the following categories: stepwise structured approaches (frameworks); measures for benefits and risks that are usually endpoint specific (metrics), simulation techniques and meta-analysis (estimation techniques), and utility survey techniques to elicit stakeholders’ preferences (utilities). All these approaches share the following two common goals: to assist this analysis and to improve the communication of decisions, but each is subject to its own specific strengths and limitations. Before using any method, its utility, complexity, the extent to which it is established, and the ease of results interpretation should be considered. Despite widespread and long-time use, BRA is subject to debate, suffers from a number of limitations, and currently is still under development. The use of formal, systematic structured approaches to BRA for regulatory decision-making and quantitative methods to support BRA during the product lifecycle is a standard practice in medicine that is subject to continuous improvement and modernization, not only in methodology but also in cooperation between organizations.

Keywords: benefit-risk assessment, benefit-risk profile, product lifecycle, quantitative methods, structured approaches

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Authors: Anna Pick Kiong Ling, Jia May Chin, Rhun Yian Koh, Ying Pei Wong

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Background: Uncontrolled inflammation may cause serious inflammatory diseases if left untreated. Non-steroidal anti-inflammatory drug (NSAIDs) is commonly used to inhibit pro-inflammatory enzymes, thus, reduce inflammation. However, long term administration of NSAIDs leads to various complications. Medicinal plants are getting more attention as it is believed to be more compatible with human body. One of them is a flavonoid-containing medicinal plants, Strobilanthes crispus which has been traditionally claimed to possess anti-inflammatory and antioxidant activities. Nevertheless, its anti-inflammatory activities are yet to be scientifically documented. Objectives: This study aimed to examine the anti-inflammatory activity of S. crispus by investigating its effects on intracellular oxidative stress and prostaglandin E₂ (PGE₂) levels. Materials and Methods: In this study, the Maximum Non-toxic Dose (MNTD) of methanol extract of both leaves and stems of S. crispus was first determined using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenytetrazolium Bromide (MTT) assay. The effects of S. crispus extracts at MNTD and half MNTD (½MNTD) on intracellular ROS as well as PGE₂ levels in 1.0 µg/mL LPS-stimulated RAW 264.7 macrophages were then be measured using DCFH-DA and a competitive enzyme immunoassay kit, respectively. Results: The MNTD of leaf extract was determined as 700µg/mL while for stem was as low as 1.4µg/mL. When LPS-stimulated RAW 264.7 macrophages were subjected to the MNTD of S. crispus leaf extract, both intracellular ROS and PGE₂ levels were significantly reduced. In contrast, stem extract at both MNTD and ½MNTD did not significantly reduce the PGE₂ level, but significantly increased the intracellular ROS level. Conclusion: The methanol leaf extract of S. crispus may possess anti-inflammatory properties as it is able to significantly reduce the intracellular ROS and PGE₂ levels of LPS-stimulated cells. Nevertheless, further studies such as investigating the interleukin, nitric oxide and cytokine tumor necrosis factor-α (TNFα) levels has to be conducted to further confirm the anti-inflammatory properties of S. crispus.

Keywords: anti-inflammatory, natural products, prostaglandin E2, reactive oxygen species

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Authors: Subas Chandra Biswas, Kazi Sameen Naser, Farzana Misha

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Little is known about the sexual behavior of male youth, particularly unmarried young men in Bangladesh as most of the sexual and reproductive health and rights-related research and intervention are mainly focused on females and married couples. To understand the unmarried youth’s sexual behavior, data from a nationwide survey conducted in all 64 districts of Bangladesh were analyzed. Using multistage systematic random sampling, a survey was conducted among 11,113 male youth aged 15-24 years from May-August, 2019. This article analyzed and presented findings of the sexual behavior of unmarried respondents based on the data collected from 10,026 unmarried male youth. Findings showed that 18% had ever experience of sexual relationship, and the reported mean age of first sexual intercourse was 16.5years. For unmarried male youth, those who had a sexual experience, their first sexual partners were female friends/classmate (57%), female neighbors (16%), and female sex workers (12%), relatives (6%) and girlfriends with whom they had love relationship (4%). However, about 36% reported that they had a love relationship with girlfriends, and among them, 23% reported that they had sexual intercourse with their girlfriend. Those who had sexual relations with their girlfriend, 47% reported that they did not use the condom in their last sex with their girlfriend. Furthermore, 29% reported that they had sexual relationships with others besides their girlfriends. Other reported partners were female sex workers (32%), neighbors (29%), female friends (19%), relatives (12%), and cousins (5%). Also, 46% reported that they did not even use the condom during sex with other partners. About 9% used some sort of sexual stimulant to increase their libido. Among the respondents, 376 reported that they bought sex in the last six months, and the mean expenditure of buying sex for the respondent was 1,140 Taka (13.46 US Dollar). Though premarital sexual relations are not socially accepted, findings showed a large portion of male youth are engaged in these relationships and risky sexual behavior. Lack of awareness of sexual and reproductive health, unprotected sexual intercourse, use of the drug during sexual intercourse also increase the threats to health. Thus these findings are important to understand the sexual behavior of male youth in policy and programmatic implications. Therefore, to ensure a healthy sexual life and wellbeing, an immediate and culturally sensitive sexual health promotion intervention is needed for male youth in Bangladesh.

Keywords: Bangladesh, male youth, sexual and reproductive health, sexual behavior

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Authors: Chia-Hsun Chang

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Background: Combination of drug treatment, dietary management, and regular exercise can effectively control type II diabetes mellitus (T2DM). Performing daily physical activities other than structured exercise is much easier and whether daily physical activities including work, walking, housework, gardening, leisure exercise, or transportation have a similar effect on diabetes control is not well studied.Aims and Objectives: This study aims to determine whether daily physical activity undertaken by patients with T2DM is associated with their diabetes control. Design: A correlation study with prospective design. Methods: Purposive sampling of 206 patients with T2DM was recruited from a medical center in Central Taiwan. The International Physical Activity Questionnaire was used to assess daily levels of physical activities, and the Diabetes Compliance Questionnaire was used to assess medication and dietary compliance. Data of diabetes control (hemoglobin A1c, HbA1c)were followed up every three months for one year after recruitment. Results: In this study, the average age of the participants was 62.5 years (±10.4 years), and the average duration of diabetes since diagnosis was 13.2 years (±7.8), 112 of the participants were women (54.4%) and 94 of the participants were men (45.6%). The mean HbA1c level was 7.8% (±1.4), and 78.2% of the participants presented with unsatisfactory diabetes control. Because the participants were distributed across a wide age range, and their physical health, activity levels, and comorbidities might have varied with age, the participants were divided into two groups: 121 participants who were younger than 65 years (58.7%) and 85 participants who were older than 65 years (41.3%). Both younger (< 65 years) and older (> 65 years) patients with diabetes engaged in more moderate and low levels of physical activity (89.3% and 87%, respectively). Results showed that the levels of daily physical activity were not significantly associated with diabetes control after adjustment for medication and dietary compliance in both groups. Conclusion: Performing daily physical activity is not significantly correlated with diabetes control. Daily physical activity cannot completely replace exercise. Relevance to Clinical Practice: Health personnel must encourage patients to engage in exercise that is planned, structured, and repetitive for improving diabetes control.

Keywords: daily physical activity, diabetes control, international physical activity questionnaire (IPAQ), type II diabetes mellitus (T2DM)

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Authors: Shikhar Shrivastava, Varun Khare

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Background: We are confronted by a society that is becoming more complex, more mobile, and more dysfunctional. Teen pregnancy, suicide, elopement, and the perusal of dangerous drugs have become commonplace. In addition, children do not settle their disputes as they once did. Guns and knives are quotidian. Therefore, it has been an exigent to have a "Juvenile Code" that would provide specific substantive and procedural rules for juveniles in the justice system. However, until the twentieth century, there was little difference between how the justice system treated adults and children. Age was considered only in terms of appropriate punishment and juveniles were eligible for the same punishment as adults. Findings: The increased prevalence and legislative support for specialized courts, Juvenile Justice Boards, including juvenile drug, mental health and truancy court programs, as well as diversion programs and evidence-based approaches into the fabric of juvenile justice are just a few examples of recent advances. In India, various measures were taken to prosecute young offenders who committed violent crimes as adults. But it was argued that equating juveniles with adult criminals was neither scientifically correct nor normatively defensible. It would defeat the very purpose of the justice system. Methodology and Conclusion: This paper attempts to bring forth the results of analytical and descriptive research that examined changing trends in juvenile justice legislation. It covers the investigative and inspective practices of police, the various administrative agencies who have roles in implementing the legislation, the courts, and the detention centers. In this paper we shall discuss about how the juvenile justice system is the dumping ground for many of a youths’ problem. The changing notions of justice, from retributive to restorative and rehabilitative shall be discussed. A comparative study of the Juvenile act in India and that of the U.S has been discussed. Specific social institutions and forces that explain juvenile delinquency are identified. In addition, various influences on juvenile delinquency are noted, such as families, schools, peer groups and communities. The text concludes by addressing socialization, deterrence, imprisonments, alternatives, restitution and preventions.

Keywords: juvenile, justice system, retributive, rehabilitative, delinquency

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Authors: Martins A. Adefisoye, Mpaka Lindelwa, Fadare Folake, Anthony I. Okoh

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Evolution and rapid dissemination of antibiotic resistance from one ecosystem to another has been responsible for wide-scale epidemic and endemic spreads of multi-drug resistance pathogens. This study assessed the prevalence of Enterobacteriaceae in different environmental samples, including river water, hospital effluents, abattoir wastewater, animal rectal swabs and faecal droppings, soil, and vegetables, using standard microbiological procedure. The identity of the isolates were confirmed using matrix-assisted laser desorption ionization-time of flight mass spectrophotometry (MALDI-TOF) while the isolates were profiled for resistance against a panel of 16 antibiotics using disc diffusion (DD) test, and the occurrence of resistance genes (ARG) was determined by polymerase chain reactions (PCR). Enterobacteriaceae counts in the samples range as follows: river water 4.0 × 101 – 2.0 × 104 cfu/100 ml, hospital effluents 1.5 × 103 – 3.0 × 107 cfu/100 ml, municipal wastewater 2.3 × 103 – 9.2 × 104 cfu/100 ml, faecal droppings 3.0 × 105 – 9.5 × 106 cfu/g, animal rectal swabs 3.0 × 102 – 2.9 × 107 cfu/ml, soil 0 – 1.2 × 105 cfu/g and vegetables 0 – 2.2 × 107 cfu/g. Of the 700 randomly selected presumptive isolates subjected to MALDI-TOF analysis, 129 (18.4%), 68 (9.7%), 67 (9.5%), 41 (5.9%) were E. coli, Klebsiella spp., Enterobacter spp., and Citrobacter spp. respectively while the remaining isolates belong to other genera not targeted in the study. The DD test shows resistance ranging between 91.6% (175/191) for cefuroxime and (15.2%, 29/191) for imipenem The predominant multiple antibiotic resistance phenotypes (MARP), (GM-AUG-AP-CTX-CXM-CIP-NOR-NI-C-NA-TS-T-DXT) occurred in 9 Klebsiella isolates. The multiple antibiotic resistance indices (MARI) the isolates (range 0.17–1.0) generally showed >95% had MARI above the 0.2 thresholds, suggesting that most of the isolates originate from high-risk environments with high antibiotic use and high selective pressure for the emergence of resistance. The associated ARG in the isolates include: bla TEM 61.9 (65), bla SHV 1.9 (2), bla OXA 8.6 (9), CTX-M-2 8.6 (9), CTX-M-9 6.7 (7), sul 2 26.7 (28), tet A 16.2 (17), tet M 17.1 (18), aadA 59.1 (62), strA 34.3 (36), aac(3)A 19.1 (20), (aa2)A 7.6 (8), and aph(3)-1A 10.5 (11). The results underscore the need for preventative measures to curb the proliferation of antibiotic-resistant bacteria including Enterobacteriaceae to protect public health.

Keywords: enterobacteriaceae, antibiotic-resistance, MALDI-TOF, resistance genes, MARP, MARI, public health

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Authors: Mohd Asharf Ganie, Aafia Rashid, Mohd Afzal Zargar, Showkat Ali Zargar, Syed Mudasar, Tabasum Parvaiz, Zafar Amin Shah

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Accumulating evidence suggests that Vitamin D deficiency (VDD) might at least contribute to the metabolic co-morbidities in PCOS. Hence, we aimed to study the effect of vitamin D supplementation in co-prescription with insulin sensitizers like metformin and pioglitazone on clinical, hormonal and metabolic parameters in women with PCOS. In this open label randomized, controlled trial a total of 120 women with PCOS diagnosis (AE-PCOS 2009 Criteria) were assigned to four treatment groups (n= 30 in each): group I (metformin 1 gm/day in combination with cholecalciferol 4000 IU/day), group II (pioglitazone 30 mg/day in combination with cholecalciferol 4000 IU/day), group III (metformin 1 gm /day) and group IV (pioglitazone 30 mg/day). Vitamin D supplementation was given as 60,000 units every two weeks for 24 weeks. All the subjects were routinely evaluated for clinical, biochemical, hormonal and insulin sensitivity parameters in addition to various safety parameters especially serum calcium levels at baseline and after 24 weeks of the treatment. Our results indicate that 95.5% of PCOS women were vitamin D deficient at baseline. Serum 25 (OH) D levels increased significantly (p < 0.001) in groups I and II without any adverse effects after 24 weeks of oral administration of 4000 IU cholecalciferol daily. However, serum 25 (OH) D levels remained unchanged in group III and IV. By six months, number of menstrual cycles per year increased whereas Ferriman-Gallwey score, serum total testosterone and HOMA-IR decreased significantly (P < 0.001) in the treatment groups supplemented with cholecalciferol as compared to those treated either drug alone. No significant beneficial changes were observed on weight, BMI, blood pressure, glucose tolerance and serum lipids in any of the groups supplemented with cholecalciferol. We conclude that daily dose of 4000 IU cholecalciferol might be a useful adjunct in complex treatment of PCOS with fewer adverse events. Furthermore, pioglitazone and cholecalciferol combination seems to be marginally better although there was no statistical significance.

Keywords: PCOS, vitamin D supplementation, insulin resistance, spironolactone, metformin, pioglitazone

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Authors: Anton V. Dolzhenko, Tahir Mehmood Khan

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An ability to make an evidence-based decision is a critically important skill required for practicing pharmacists. The development of this skill is incorporated into the pharmacy curriculum. We aimed in our study to estimate perception of pharmacy students regarding herbal medicines and their ability to assess information on herbal medicines professionally. The current Monash University curriculum in Pharmacy does not provide comprehensive study material on herbal medicines and students should find their way to find information, assess its quality and make a professional decision. In the Pharmacy course, students are trained how to apply this process to conventional medicines. In our survey of 93 undergraduate students from year 1-4 of Pharmacy course at Monash University Malaysia, we found that students’ view on herbal medicines is sometimes associated with common beliefs, which affect students’ ability to make evidence-based conclusions regarding the therapeutic potential of herbal medicines. The use of herbal medicines is widespread and 95.7% of the participated students have prior experience of using them. In the scale 1 to 10, students rated the importance of acquiring herbal medicine knowledge for them as 8.1±1.6. More than half (54.9%) agreed that herbal medicines have the same clinical significance as conventional medicines in treating diseases. Even more, students agreed that healthcare settings should give equal importance to both conventional and herbal medicine use (80.6%) and that herbal medicines should comply with strict quality control procedures as conventional medicines (84.9%). The latter statement also indicates that students consider safety issues associated with the use of herbal medicines seriously. It was further confirmed by 94.6% of students saying that the safety and toxicity information on herbs and spices are important to pharmacists and 95.7% of students admitting that drug-herb interactions may affect therapeutic outcome. Only 36.5% of students consider herbal medicines as s safer alternative to conventional medicines. The students use information on herbal medicines from various sources and media. Most of the students (81.7%) obtain information on herbal medicines from the Internet and only 20.4% mentioned lectures/workshop/seminars as a source of such information. Therefore, we can conclude that students attained the skills on the critical assessment of therapeutic properties of conventional medicines have a potential to use their skills for evidence-based decisions regarding herbal medicines.

Keywords: evidence-based decision, pharmacy education, student perception, traditional medicines

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Authors: Diana C. El Assal, Fatima Monteiro, Caroline May, Peter Barbuti, Silvia Bolognin, Averina Nicolae, Hulda Haraldsdottir, Lemmer R. P. El Assal, Swagatika Sahoo, Longfei Mao, Jens Schwamborn, Rejko Kruger, Ines Thiele, Kathrin Marcus, Ronan M. T. Fleming

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Degeneration of substantia nigra pars compacta dopaminergic neurons is one of the hallmarks of Parkinson's disease. These neurons have a highly complex axonal arborisation and a high energy demand, so any reduction in ATP synthesis could lead to an imbalance between supply and demand, thereby impeding normal neuronal bioenergetic requirements. Synaptic mitochondria exhibit increased vulnerability to dysfunction in Parkinson's disease. After biogenesis in and transport from the cell body, synaptic mitochondria become highly dependent upon oxidative phosphorylation. We applied a systems biochemistry approach to identify the metabolic pathways used by neuronal mitochondria for energy generation. The mitochondrial component of an existing manual reconstruction of human metabolism was extended with manual curation of the biochemical literature and specialised using omics data from Parkinson's disease patients and controls, to generate reconstructions of synaptic and somal mitochondrial metabolism. These reconstructions were converted into stoichiometrically- and fluxconsistent constraint-based computational models. These models predict that Parkinson's disease is accompanied by an increase in the rate of glycolysis and a decrease in the rate of oxidative phosphorylation within synaptic mitochondria. This is consistent with independent experimental reports of a compensatory switching of bioenergetic pathways in the putamen of post-mortem Parkinson's disease patients. Ongoing work, in the context of the SysMedPD project is aimed at computational prediction of mitochondrial drug targets to slow the progression of neurodegeneration in the subset of Parkinson's disease patients with overt mitochondrial dysfunction.

Keywords: bioenergetics, mitochondria, Parkinson's disease, systems biochemistry

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