Search results for: veterinary treatment

Authors: Sharif Abdelghany

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Polymeric nanoparticles have been widely investigated as a controlled release drug delivery platform for the treatment of tuberculosis (TB). These nanoparticles were also readily internalised into macrophages, leading to high intracellular drug concentration. In this study two anti-TB drugs, amikacin and moxifloxacin were encapsulated into PLGA nanoparticles. The novelty of this work appears in: (1) the efficient encapsulation of two hydrophilic second-line anti-TB drugs, and (2) intramacrophage delivery of this synergistic combination potentially for rapid treatment of multi-drug resistant TB (MDR-TB). Two water-oil-water (w/o/w) emulsion strategies were employed in this study: (1) alginate coated PLGA nanoparticles, and (2) alginate entrapped PLGA nanoparticles. The average particle size and polydispersity index (PDI) of the alginate coated PLGA nanoparticles were found to be unfavourably high with values of 640 ± 32 nm and 0.63 ± 0.09, respectively. In contrast, the alginate entrapped PLGA nanoparticles were within the desirable particle size range of 282 - 315 nm and the PDI was 0.08 - 0.16, and therefore were chosen for subsequent studies. Alginate entrapped PLGA nanoparticles yielded a drug loading of over 10 µg/mg powder for amikacin, and more than 5 µg/mg for moxifloxacin and entrapment efficiencies range of approximately 25-31% for moxifloxacin and 51-59% for amikacin. To study macrophage uptake efficiency, the nanoparticles of alginate entrapped nanoparticle formulation were loaded with acridine orange as a marker, seeded to THP-1 derived macrophages and viewed under confocal microscopy. The particles were readily internalised into the macrophages and highly concentrated in the nucleus region. Furthermore, the anti-mycobacterial activity of the drug-loaded particles was evaluated using M. tuberculosis-infected macrophages, which revealed a significant reduction (4 log reduction) of viable bacterial count compared to the untreated group. In conclusion, the amikacin-moxifloxacin alginate entrapped PLGA nanoparticles are promising for further in vivo studies.

Keywords: moxifloxacin and amikacin, nanoparticles, multidrug resistant TB, PLGA

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Authors: Drago Bratkovic, Curtis Gravance, David Ketteridge, Ravi Krishnan, Michael Imperiale

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The mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases that have a common defect in the catabolism of glycosaminoglycans (GAGs). MPS I is the most common of the MPS diseases. Manifestations of MPS I include coarsening of facial features, corneal clouding, developmental delay, short stature, skeletal manifestations, hearing loss, cardiac valve disease, hepatosplenomegaly, and umbilical and inguinal hernias. Treatments for MPS I restore or activate the missing or deficient enzyme in the case of enzyme replacement therapy (ERT) and haematopoietic stem cell transplantation (HSCT). Pentosan polysulfate sodium (PPS) is a potential treatment to improve bone and joint manifestations of MPS I. The mechanisms of action of PPS that are relevant to the treatment of MPS I are the ability to: (i) Reduce systemic and accumulated GAG, (ii) Reduce inflammatory effects via the inhibition of NF-kB, resulting in the reduction in pro-inflammatory mediators. (iii) Reduce the expression of the pain mediator nerve growth factor in osteocytes from degenerating joints. (iv) Inhibit the cartilage degrading enzymes related to joint dysfunction in MPS I. PPS is being evaluated as an adjunctive therapy to ERT and/or HSCT in an open-label, single-centre, phase 2 study. Patients are ≥ 5 years of age with a diagnosis of MPS I and previously received HSCT and/or ERT. Three white, female, patients with MPS I-Hurler, ages 14, 15, and 19 years, and one, white male patient aged 15 years are enrolled. All were diagnosed at ≤2 years of age. All patients received HSCT ≤ 6 months after diagnosis. Two of the patients were treated with ERT prior to HSCT, and 1 patient received ERT commencing 3 months prior to HSCT. Two patients received 0.75mg/kg and 2 patients received 1.5mg/kg of PPS. PPS was well tolerated at doses of 0.75 and 1.5 mg/kg to 47 weeks of continuous dosing. Of the 19 adverse events (AEs), 2 were related to PPS. One AE was moderate (pre-syncope) and 1 was mild (injection site bruising), experienced in the same patient. All AEs were reported as mild or moderate. There have been no SAEs. One subject experienced a COVID-19 infection and PPS was interrupted. The MPS I signature GAG fragments, sulfated disaccharide and UA-HNAc S, tended to decrease in 3 patients from baseline through Week 25. Week 25 GAG data are pending for the 4th patient. Overall, most biomarkers (inflammatory, cartilage degeneration, and bone turnover) evaluated in the 3 patients with 25-week assessments have indicated either no change or a reduction in levels compared to baseline. In 3 patients, there was a trend toward improvement in the 2MWT from baseline to Week 48 with > 100% increase in 1 patient (01-201). In the 3 patients that had Week 48 assessments, patients and proxies reported improvement in PGIC, including “worthwhile difference” (n=1), or “made all the difference” (n=2).

Keywords: MPS I, pentosan polysulfate sodium, clinical study, 2MWT, QoL

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Authors: Kaling Taki, Rohit Gahlot, Manish Kumar

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Disposal of Sewage Sludge (SS) is a big issue especially in developing nation like India, where there is no control in the dynamicity of SS produced. The present research work demonstrates the potential application of SS amended with varying percentage (0-100%) of Fly Ash (FA) for brick manufacturing as an alternative of SS management. SS samples were collected from Jaspur sewage treatment plant (Ahmedabad, India) and subjected to different preconditioning treatments: (i) atmospheric drying (ii) pulverization (iii) heat treatment in oven (110°C, moisture removal) and muffle furnace (440°C, organic content removal). Geotechnical parameters of the SS were obtained as liquid limit (52%), plastic limit (24%), shrinkage limit (10%), plasticity index (28%), differential free swell index (DFSI, 47%), silt (68%), clay (27%), organic content (5%), optimum moisture content (OMC, 20%), maximum dry density (MDD, 1.55gm/cc), specific gravity (2.66), swell pressure (57kPa) and unconfined compressive strength (UCS, 207kPa). For FA liquid limit, plastic limit and specific gravity was 44%, 0% and 2.2 respectively. Initially, for brick casting pulverized SS sample was heat treated in a muffle furnace around 440℃ (5 hours) for removal of organic matter. Later, mixing of SS, FA and water by weight ratio was done at OMC. 7*7*7 cm3 sample mold was used for casting bricks at MDD. Brick samples were then first dried in room temperature for 24 hours, then in oven at 100℃ (24 hours) and finally firing in muffle furnace for 1000℃ (10 hours). The fired brick samples were then cured for 3 days according to Indian Standards (IS) common burnt clay building bricks- specification (5th revision). The Compressive strength of brick samples (0, 10, 20, 30, 40, 50 ,60, 70, 80, 90, 100%) of FA were 0.45, 0.76, 1.89, 1.83, 4.02, 3.74, 3.42, 3.19, 2.87, 0.78 and 4.95MPa when evaluated through compressive testing machine (CTM) for a stress rate of 14MPa/min. The highest strength was obtained at 40% FA mixture i.e. 4.02MPa which is much higher than the pure SS brick sample. According to IS 1077: 1992 this combination gives strength more than 3.5 MPa and can be utilized as common building bricks. The loss in weight after firing was much higher than the oven treatment, this might be due to degradation temperature higher than 100℃. The thermal conductivity of the fired brick was obtained as 0.44Wm-1K-1, indicating better insulation properties than other reported studies. TCLP (Toxicity characteristic leaching procedure) test of Cr, Cu, Co, Fe and Ni in raw SS was found as 69, 70, 21, 39502 and 47 mg/kg. The study positively concludes that SS and FA at optimum ratio can be utilized as common building bricks such as partitioning wall and other small strength requirement works. The uniqueness of the work is it emphasizes on utilization of FA for stabilizing SS as construction material as a replacement of natural clay as reported in existing studies.

Keywords: Compressive strength, Curing, Fly Ash, Sewage Sludge.

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Authors: Oluyomi Stephen Adeyemi, Kentaro Kato

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Toxoplasma gondii is the etiological agent of toxoplasmosis, a common parasitic disease capable of infecting a range of hosts, including nearly one-third of the human population. Current treatment options for toxoplasmosis patients are limited. In consequence, toxoplasmosis represents a large global burden that is further enhanced by the shortcomings of the current therapeutic options. These factors underscore the need for better anti-T. gondii agents and/or new treatment approach. In the present study, we sought to find out whether preparing and capping nanoparticles (NPs) in amino acids, would enhance specificity toward the parasite versus the host cell. The selection of amino acids was premised on the fact that T. gondii is auxotrophic for some amino acids. The amino acid-nanoparticles (amino-NPs) were synthesized, purified and characterized following established protocols. Next, we tested to determine the anti-T. gondii activity of the amino-NPs using in vitro experimental model of infection. Overall, our data show evidence that supports enhanced and excellent selective action against the parasite versus the host cells by amino-NPs. The findings are promising and provide additional support that warrants exploring the prospects of NPs as alternative anti-parasite agents. In addition, the anti-parasite action by amino-NPs indicates that nutritional requirement of parasite may represent a viable target in the development of better alternative anti-parasite agents. Furthermore, data suggest the anti-parasite mechanism of the amino-NPs involves multiple cellular processes including the production of reactive oxygen species (ROS), modulation of hypoxia-inducing factor-1 alpha (HIF-1α) as well as the activation of kynurenine pathway. Taken together, findings highlight further, the prospects of NPs as alternative source of anti-parasite agents.

Keywords: drug discovery, infectious diseases, mode of action, nanomedicine

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Authors: Chioma J. Nwakamma, Blessing O. Oyedemi, Garuba Omosun

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This research surveys and documents information on medicinal plants and their botanical preparations used in the treatment of children’s ailments in South-Eastern Nigeria. Children under the age of 5 in developing countries suffer from diseases with high morbidity and mortality rate yearly due to inaccessible and unaffordable healthcare. Structured questionnaires were administered to herbal sellers, traditional medicine practitioners, nursing mothers, and adult dwellers to collect data on the names of plants used to treat the conditions, methods of preparation, duration of treatment, adverse effects, and the methods of administration of the plant materials. A total of 135 plants belonging to 55 families were identified for the management of children’s health in the area. Common pediatric ailments which were said to be treated with herbal remedies by the respondents included malaria, pneumonia, stomach ache, diarrhea, dysentery, measles, chickenpox/smallpox, convulsion, jaundice, pile, ringworm, scabies, eczema, stubborn cough, scurvy, catarrh, wounds, boils, insect bites, food poison, cholera, and umbilical cord complications. Percentages of respondents were; herbal sellers (48.2%), traditional medical practitioners (21.6%), nursing mothers (11.1%), and others (19.1%). The most occurring plant families were Euphorbiaceae, Fabaceae, and Apocynaceae, with 8 species of plants each followed by Annonaceae and Asteriaceae with 7 and 6 species, respectively. The recipes were made from the combination of different parts of two or more plant species, and others were made from single plant parts. Methods of extraction were mostly decoction and raw-squeezing out of the juice and infusion, while oral administration was the main route of administration.

Keywords: ethno-botanicals, children’s health, medicinal plants, South-Eastern Nigeria

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Authors: Yenesew Mengiste Yihun, Abraham Mehari Haile, Teklu Erkossa, Bart Schultz

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Teff (Eragrostic tef) is a staple food in Ethiopia. The local and international demand for the crop is ever increasing pushing the current price five times compared with that in 2006. To meet this escalating demand increasing production including using irrigation is imperative. Optimum application of irrigation water, especially in semi-arid areas is profoundly important. AquaCrop model application in irrigation water scheduling and simulation of water productivity helps both irrigation planners and agricultural water managers. This paper presents simulation and evaluation of AquaCrop model in optimizing the yield and biomass response to variation in timing and rate of irrigation water application. Canopy expansion, canopy senescence and harvest index are the key physiological processes sensitive to water stress. For full irrigation water application treatment there was a strong relationship between the measured and simulated canopy and biomass with r2 and d values of 0.87 and 0.96 for canopy and 0.97 and 0.74 for biomass, respectively. However, the model under estimated the simulated yield and biomass for higher water stress level. For treatment receiving full irrigation the harvest index value obtained were 29%. The harvest index value shows generally a decreasing trend under water stress condition. AquaCrop model calibration and validation using the dry season field experiments of 2010/2011 and 2011/2012 shows that AquaCrop adequately simulated the yield response to different irrigation water scenarios. We conclude that the AquaCrop model can be used in irrigation water scheduling and optimizing water productivity of Teff grown under water scarce semi-arid conditions.

Keywords: AquaCrop, climate smart agriculture, simulation, teff, water security, water stress regions

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Authors: Mariem Meddeb Sidhom, Souhayel Hedfi, Rjaibia Houda, Mehdi Dridi, Mohamed Ali Yousfi, Sâadia Gargouri

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Considering the important increase in costs of caspofungin treatments and ahead the evolution of its indication, pharmacy department was prompted to realize a review of the adequacy of prescriptions in the medical intensive care units (ICU). A retrospective observational study was conducted in Tunis military hospital concerning ICU prescriptions of caspofungin from 2008 until 2013. A pharmacist had returned to the patient’s medical records to collect data and to the microbiology department for parasitological results. The adequacy of prescriptions was evaluated by a pharmacist and an infectiologist parasitologist, referring to predefined scale of criteria resuming the indications of the marketing authorization (MA) and grade AI-AII of the guidelines of the Infectious Diseases Society of America (IDSA). Sixty two ICU patients have been treated with caspofungin during the period of study; however, 8 files were lost. Thus, 54 patients were included in the study having received 55 prescriptions of caspofungin. Males were a majority with 64.8% of the population. Mean age was 51 years. Caspofungin was indicated in accordance with the IDSA recommendations in 43.6% of the cases. The most case of non respect to the guidelines was the indication of caspofungin as empirical treatment in non neutropenic patients. Caspofungin was utilized as a first line treatment in 9 cases where it was possible to give fluconazole first, as germs were fluconazole- sensitive. Caspofungin was indicated in 2 patients with good renal function and in which nor amphotericin B, liposomal ampho B neither itraconazole had been previously used, as indicates the MA. The posology of caspofungin was respected in all prescriptions with a loading dose of 70 mg in the first day and a maintenance dose of 50 mg daily. Seven patients had received a daily dose of 70 mg, the recommended dose for people weighing more than 80 Kg. Caspofungin prescriptions are far to be adequately done. There is a clear need of optimization in indicating this molecule and that must be done in collaboration between the pharmacy department, the ICUs and parasitology department.

Keywords: caspofungin, prescription, intensive care units, marketing authorization, Tunisian hospital cohort

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Authors: Oleg Sapelnikov, Ruslan Latypov, Darina Ardus, Samvel Aivazian, Andrey Shiryaev, Renat Akchurin

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OBJECTIVE: MAZE procedure is one of the most effective surgical methods in atrial fibrillation (AF) treatment. Nowadays we are all aware of its modifications. In our study we conducted clinical analysis of “Box lesion+” approach during MAZE procedure in two-year follow-up. METHODS: We studied the results of the open-heart on-pump procedures performed in our hospital from 2017 to 2018 years. Thirty-two (32) patients with atrial fibrillation (AF) were included in this study. Fifteen (15) patients had concomitant coronary bypass grafting and seventeen (17) patients had mitral valve repair. Mean age was 62.3±8.7 years; prevalence of men was admitted (56.1%). Mean duration of AF was 4.75±5.44 and 7.07±8.14 years. In all cases, we performed endocardial Cryo-MAZE procedure with one-time myocardium revascularization or mitral-valve surgery. All patients of this study underwent pulmonary vein (PV) isolation and ablation of mitral isthmus with additional isolation of LA posterior wall (Box-lesion+ procedure). Mean follow-up was 2 years. RESULTS: All cases were performed without any complications. Additional isolation of posterior wall did not prolong the operative time and artificial circulation significantly. Cryo-MAZE procedure directly lasted 20±2.1 min, the whole operation time was 192±24 min and artificial circulation time was 103±12 min. According to design of the study, we performed clinical investigation of the patients in 12 months and in 2 years from the initial procedure. In 12 months, the number of AF free patients 81.8% and 75.8% in two years of follow-up. CONCLUSIONS: Isolation of the left atrial posterior wall and perimitral area may considerably improve the efficacy of surgical treatment, which was demonstrated in significant decrease of AF recurrences during the whole period of follow-up.

Keywords: atrial fibrillation, cryoablation, left atrium isolation, open heart procedure

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Authors: A. Ghribi, M. Bagane

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The discharge of dye in industrial effluents is of great concern because their presence and accumulation have a toxic or carcinogenic effect on living species. The removal of such compounds at such low levels is a difficult problem. The adsorption process is an effective and attractive proposition for the treatment of dye contaminated wastewater. Activated carbon adsorption in fixed beds is a very common technology in the treatment of water and especially in processes of decolouration. However, it is expensive and the powdered one is difficult to be separated from aquatic system when it becomes exhausted or the effluent reaches the maximum allowable discharge level. The regeneration of exhausted activated carbon by chemical and thermal procedure is also expensive and results in loss of the sorbent. The focus of this research was to evaluate the adsorption potential of the raw clay in removing rhodamine B from aqueous solutions using a laboratory fixed-bed column. The continuous sorption process was conducted in this study in order to simulate industrial conditions. The effect of process parameters, such as inlet flow rate, adsorbent bed height, and initial adsorbate concentration on the shape of breakthrough curves was investigated. A glass column with an internal diameter of 1.5 cm and height of 30 cm was used as a fixed-bed column. The pH of feed solution was set at 8.5. Experiments were carried out at different bed heights (5 - 20 cm), influent flow rates (1.6- 8 mL/min) and influent rhodamine B concentrations (20 - 80 mg/L). The obtained results showed that the adsorption capacity increases with the bed depth and the initial concentration and it decreases at higher flow rate. The column regeneration was possible for four adsorption–desorption cycles. The clay column study states the value of the excellent adsorption capacity for the removal of rhodamine B from aqueous solution. Uptake of rhodamine B through a fixed-bed column was dependent on the bed depth, influent rhodamine B concentration, and flow rate.

Keywords: adsorption, breakthrough curve, clay, fixed bed column, rhodamine b, regeneration

Procedia PDF Downloads 277

Authors: A. Abdulkadir, Y. M. Bello, A. A. Okhimamhe, H. Ibrahim, M. B. Matazu, L. S. Barau

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The increasing volume of solid waste generated, collected and disposed daily complicate adequate management of solid waste by the relevant agency like Niger State Environmental Protection Agency (NISEPA). In addition, the impacts of solid waste on the natural environment and human livelihood require identification of cost-effective ways for sustainable municipal waste management in Nigeria. These signal the need for identifying environment-friendly initiative and local solution to address municipal solid waste. A research field was secured at Pago, Minna, Niger State which is located in the guinea savanna belt of Nigeria, within longitude 60 3614311- 4511 and latitude 90 291 37.6111- .6211 N. Poultry droppings, decomposed household waste manure and NPK treatment were used. The experimental field was divided into three replications and four (4) treatments on each replication making a total of twelve (12) plots. The treatments were allotted using Randomized Complete Block Design (RCBD) and Data collected was analyzed using SPSS software and RCBD. The result depicts variation in plant height and number of leaves at 50% flowering; Poultry dropping records the highest height as a number of leaves for waste manure competes fairly well with NPK treatment. Similarly, the varying treatments significantly increase vegetable yield, as the control (Nontreatment) records the least yield for the three vegetable samples. Adoption of this organic manure for cultivation does not only enhance environment quality and attainment of food security but will contribute to local economic development, poverty alleviation, and social inclusion.

Keywords: environmental issues, food security, NISEPA, solid waste

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Authors: Pham Minh Duc, Tran Thi Thanh Hien, David A. Bengtson

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Laboratory feeding trial: the study was conducted to find out the optimal dietary vitamin C, or ascorbic acid (AA) levels in terms of the growth performance of snakehead. The growth trial included six treatments with five replications. Each treatment contained 0, 125, 250, 500, 1000 and 2000 mg AA equivalent kg⁻¹ diet which included six iso-nitrogenous (45% protein), iso-lipid (9% lipid) and isocaloric (4.2 Kcal.g¹). Eighty snakehead fingerlings (6.24 ± 0.17 g.fish¹) were assigned randomly in 0.5 m³ composite tanks. Fish were fed twice daily on demand for 8 weeks. The result showed that growth rates increased, protein efficiency ratio increased and the feed conversion ratio decreased in treatments with AA supplementation compared with control treatment. The survival rate of fish tends to increase with increase AA level. The number of RBCs, lysozyme in treatments with AA supplementation tended to rise significantly proportional to the concentration of AA. The number of WBCs of snakehead in treatments with AA supplementation was higher 2.1-3.6 times. In general, supplementation of AA in the diets for snakehead improved growth rate, feed efficiency and immune response. Hapa on-farm trial: based on the results of the laboratory feeding trial, the effects of AA on snakehead in hapas to simulate farm conditions, was tested using the following treatments: commercial feed; commercial feed plus hand mixed AA at 500; 750 and 1000 mg AA.kg⁻¹; SBM diet without AA; SBM diet plus 500; 750 and 1000 mg AA.kg⁻¹. The experiment was conducted in two experimental ponds (only SBM diet without AA placed in one pond and the rest in the other pond) with four replicate hapa each. Stocking density was 150 fish.m² and culture period was 5 months until market size was attained. The growth performance of snakehead and economic aspects were examined in this research.

Keywords: fish health, growth rate, snakehead, Vitamin C

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Authors: O.F. Akinmoladun, F.N. Fon, C.T. Mpendulo, O. Okoh

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The sustainability of livestock production is under threat as a result of water scarcity, fluctuating precipitation, and high environmental temperature. These combined stressors have impacted negatively on general animal production and welfare, necessitating a very reliable and cost-effective management practices, especially in arid and water-limited regions of the world. Instead of the above, this study was designed to investigate the growth performance and physiological response of water-restricted Xhosa ear-lobe goats fed diets supplemented with single or multiple vitamin C (VC) during summer. The total forty-eight goats used for the experiment were balanced for body weight and randomly assigned to the seven treatment groups (seven goats/treatment): GI (W100%); GII (W70%); GIII (W50%); GIV (W70%+3g/day VC); GV ((W50% +3g/day VC); GVI (W70%+3g/d VC+extra 5g on every eight-day); GVII (W50%+3g/d VC+extra 5g on every eight-day). The design was a complete randomized design and VC was administered per os. At the end of the 75-day feeding trial, GIII (W50%) animals were the most affected (P<0.05) and the effect was more pronounced in their body condition scores (BCs). Weight loss and depression in feed intake due to water restriction (P<0.05) were attenuated by VC treated groups (GIV-GVII). Changes in body thermal gradient (BTG) and rectal temperature (RcT) were similar (P>0.05) across the various experimental groups. The attenuation effect of VC was significant in responses to respiratory rate (RR) and cortisol. Supplementation of VC (either single or multiple) did not significantly (P>0.05) improve water restriction effect on body condition scores (BCs) and FAMACHA©. The current study found out that Xhosa ear lobe goats can adapt to the prevailing bioclimatic changes and limited water intake. However, supplementation of vitamin C can be beneficial at modulating these stressful stimuli. Continuous consistencies in the outcome of vitamin C on water-stressed animals can help validate recommendations especially to farmers in the arid and water-limited regions across the globe.

Keywords: vitamin C, Xhosa ear-lobe, thermotolerance, water stress

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Authors: Ibrahim M. Labouta, Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Tamer M. Ibrahim, Nefertiti A. El-Nikhely

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Bruton’s tyrosine kinase (BTK) is a critical effector molecule in B cell antigen receptor (BCR) signaling transduction. It regulates B cell proliferation, development and survival. Since BTK is widely expressed in many B cell leukaemias and lymphomas, targeting BTK by small molecules inhibitors became an attractive idea as new treatment modalities for B cell mediated hematologic malignancies. Ibrutinib is the 1st generation BTK inhibitor, approved by FDA for treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). It binds irreversibly to the unique cysteine (Cys481) within the ATP-binding pocket of BTK. Besides ibrutinib, many irreversible covalent BTK inhibitors comprising pyrimidine nucleus such as spebrutinib (phase IIb) showed high selectivity and potency when compared to it. In this study, the designed compounds were based on 5-cyano-2-methylsulfanyl pyrimidine core and decorated with electrophilic warheads which are essential for the optimal activity for targeted covalent inhibition (TCI). However, modifications at pyrimidine C4 or C6 were made by introduction of substituted amines which are provided to behave differently. The synthesized derivatives were evaluated for their anticancer activity in leukemia cell lines (e.g. THP-1). Results showed that, some derivatives exhibited antiproliferative activity with IC50 ranged from 5-50 μM, The in vitro enzymatic inhibitory assay for these compounds against BTK is still under investigation. Nevertheless, we could conclude from the initial biological screening that, the synthesized 4 or 6-subsitituted aminopyrimidines represent promising and novel antileukemic agents. Meanwhile, further studies are still needed to attribute this activity through targeting BTK enzyme and inhibition of BCR signaling pathway.

Keywords: BTK inhibitors, hematologic malignancies, structure based drug design (SBDD), targeted covalent inhibitors (TCI)

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Authors: Miguel A. Jimenez Barros, Elyn L. Solano Charris, Luis E. Ramirez, Lauren Castro Bolano, Carlos Torres Barreto, Juliana Morales Cubillo

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This project sought to mitigate the high levels of water consumption in industrial processes in accordance with the water-rationing plan promoted at national and international level due to the water consumption projections published by the United Nations. Water consumption has three main uses, municipal (common use), agricultural and industrial where the latter consumes a minimum percentage (around 20% of the total consumption). Awareness on world water scarcity, a Colombian company responsible for generation of massive consumption products, decided to implement politics and techniques for water treatment, recycling, and reuse. The project consisted in a business technology program that permits a better use of wastewater caused by production operations. This approach reduces the potable water consumption, generates better conditions of water in the sewage dumps, generates a positive environmental impact for the region, and is a reference model in national and international levels. In order to achieve the objective, a process flow diagram was used in order to define the industrial processes that required potable water. This strategy allowed the industry to determine a water reuse plan at the operational level without affecting the requirements associated with the manufacturing process and even more, to support the activities developed in administrative buildings. Afterwards, the company made an evaluation and selection of the chemical and biological processes required for water reuse, in compliance with the Colombian Law. The implementation of the business technology program optimized the water use and recirculation rate up to 70%, accomplishing an important reduction of the regional environmental impact.

Keywords: bio-reactor, potable water, reverse osmosis, water treatment

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Authors: T. Poyai, P. Painmanakul, N. Chawaloesphonsiya, P. Dhanasin, C. Getwech, P. Wattana

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Drilling is a key activity in oil and gas exploration and production. Drilling always requires the use of drilling mud for lubricating the drill bit and controlling the subsurface pressure. As drilling proceeds, a considerable amount of cuttings or rock fragments is generated. In general, water or Water Based Mud (WBM) serves as drilling fluid for the top hole section. The cuttings generated from this section is non-hazardous and normally applied as fill materials. On the other hand, drilling the bottom hole to reservoir section uses Synthetic Based Mud (SBM) of which synthetic oils are composed. The bottom-hole cuttings, SBM cuttings, is regarded as a hazardous waste, in accordance with the government regulations, due to the presence of hydrocarbons. Currently, the SBM cuttings are disposed of as an alternative fuel and raw material in cement kiln. Instead of burning, this work aims to propose an alternative for drill cuttings management under two ultimate goals: (1) reduction of hazardous waste volume; and (2) making use of the cleaned cuttings. Soil washing was selected as the major treatment process. The physiochemical properties of drill cuttings were analyzed, such as size fraction, pH, moisture content, and hydrocarbons. The particle size of cuttings was analyzed via light scattering method. Oil present in cuttings was quantified in terms of total petroleum hydrocarbon (TPH) through gas chromatography equipped with flame ionization detector (GC-FID). Other components were measured by the standard methods for soil analysis. Effects of different washing agents, liquid-to-solid (L/S) ratio, washing time, mixing speed, rinse-to-solid (R/S) ratio, and rinsing time were also evaluated. It was found that drill cuttings held the electrical conductivity of 3.84 dS/m, pH of 9.1, and moisture content of 7.5%. The TPH in cuttings existed in the diesel range with the concentration ranging from 20,000 to 30,000 mg/kg dry cuttings. A majority of cuttings particles held a mean diameter of 50 µm, which represented silt fraction. The results also suggested that a green solvent was considered most promising for cuttings treatment regarding occupational health, safety, and environmental benefits. The optimal washing conditions were obtained at L/S of 5, washing time of 15 min, mixing speed of 60 rpm, R/S of 10, and rinsing time of 1 min. After washing process, three fractions including clean cuttings, spent solvent, and wastewater were considered and provided with recommendations. The residual TPH less than 5,000 mg/kg was detected in clean cuttings. The treated cuttings can be then used for various purposes. The spent solvent held the calorific value of higher than 3,000 cal/g, which can be used as an alternative fuel. Otherwise, the recovery of the used solvent can be conducted using distillation or chromatography techniques. Finally, the generated wastewater can be combined with the produced water and simultaneously managed by re-injection into the reservoir.

Keywords: drill cuttings, green solvent, soil washing, total petroleum hydrocarbon (TPH)

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Authors: Kasra Afsahi, Maryam Soheilifar, S. Hossein Hosseini, Omid Seyed Esmaeili, Rouzbeh Kezemi, Noushin Mehrbod, Nazanin Vahed, Tahereh Hajiahmad, Noureddin Nakhostin Ansari

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Background: Stroke is a disabling neurological disease. Rehabilitative therapies are important treatment methods. This clinical trial was done to compare the effects of VR beside conventional rehabilitation versus conventional rehabilitation alone on spasticity and motor function in stroke patients. Materials and Methods: In this open-label randomized controlled clinical trial, 40 consecutive patients with stable first-ever ischemic stroke in the past three to 12 months that were referred to a rehabilitation clinic in Tehran, Iran, in 2020 were enrolled. After signing the informed written consent form, subjects were randomly assigned by block randomization of five in each block as cases with 1:1 into two groups of 20 cases; conventional plus VR therapy group: 45-minute conventional therapy session plus 15-minute VR therapy, and conventional group: 60-minute conventional therapy session. VR rehabilitation is designed and developed with different stages. Outcomes were modified Ashworth scale, recovery stage score for motor function, range of motion (ROM) of shoulder abduction/wrist extension, and patients’ satisfaction rate. Data were compared after study termination. Results: The satisfaction rate among the patients was significantly better in the combination group (P=0.003). Only wrist extension was varied between groups and was better in the combination group. The variables generally had a statistically significant difference (P < 0.05). Conclusion: Virtual reality plus conventional rehabilitation therapy is superior versus conventional rehabilitation alone on the wrist and elbow spasticity and motor function in patients with stroke.

Keywords: stroke, virtual therapy, rehabilitation, treatment

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Authors: Okunola Oluseye Ademola

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The study investigated various socio-cultural factors influencing adherence to antiretroviral drugs among people living with HIV in a University Teaching Hospital in South-western Nigeria. The objectives are to examine the perception of people living with HIV/AIDS (PLWHA) of antiretroviral therapy (ART) in Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, investigate the influence of socio-cultural factors on adherence of PLWHA to treatment regimen in the study area and assess the prevalence of adherence to ART among PLWHA in the study area. It was a cross-sectional where both qualitative and quantitative research methods were adopted. The participants were HIV diagnosed patients attending clinic at the Obafemi Awolowo University Teaching Hospitals Complex in Ile-Ife between the ages of 18 and 60 years. Also three healthcare delivery personnel working in the clinic were interviewed. Out of the 3007 patients receiving treatment, using Fischer’s formula of sampling technique, 336 patients living with HIV/AIDS were selected for the study. These participants had been on antiretroviral drugs for more than six months prior to the study and were selected using simple random sampling technique. Two focus group discussion sessions comprising of 10 male and 10 female living with HIV and currently on ART were conducted. These groups were purposively selected based on their being on ART for more than one year. Also in-depth interviews were conducted among three purposively selected healthcare givers (an experienced nurse, a doctor and a pharmacist) who are working in this clinic. All the participants were interviewed at the clinic on the various clinic days. Data were collected using a structured questionnaire, an interview guide and tape-recorder. The quantitative data were analysed using descriptive and inferential statistics. Content analysis was employed to analyse responses from IDI and FGD sessions. The findings from the study revealed a very positive perception to ART among PLWHA which was about 86.3% while the level of adherence to ART was 89.0% among the respondents. There was a very strong relationship between social and family supports and the degree of adherence to ART in the PLWHA. Nutrition, polygamy, difficulty in financing transportation fare to the clinic, unemployment, drug hawkers, religion, excuse duty from work and waking up very early were highlighted as socio-cultural barriers to adherence to ART. Fear of death, strong family support, religion belief, not seeking alternative treatment, absence of rituals and perceived improved health status were identified as very strong facilitators to adherence. The study concluded that to achieve a very optimal outcome in the management of HIV among PLWHA, various social and cultural contexts should be taken into consideration as this study was able to ascertain the influence of various socio-cultural factors militating and facilitating adherence to ART.

Keywords: ART, HIV, PLWHA, socio-cultural

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Authors: Nitin Kumar

Abstract:

Purpose: The current research work focuses mainly on evolving a delivery system for ginseng extract (GE), which in turn will ameliorate the neuroprotective potential by means of enhancing the ginsenoside (Rb1) bio-availability (BA). For more noteworthy enhancement in oral bioavailability (OBA) along with pharmacological properties, the drug carriers’ performance can be strengthened by utilizing phytosomes-loaded microspheres (PM) delivery system. Methods: For preparing the disparate phytosome complexes (F1, F2, and F3), an aqueous extract of ginseng roots (GR) along with phospholipids were reacted in disparate ratio. Considering the outcomes, F3 formulation (spray-dried) was chosen for preparing the phytosomes powder (PP), PM, and extract microspheres (EM). PM was made by means of loading of F3 into Gum Arabic (GA) in addition to maltodextrin polymer mixture, whereas EM was prepared by means of the addition of extract directly into the same polymer mixture. For investigating the neuroprotective effect (NPE) in addition to their pharmacokinetic (PK) properties, PP, PM, and EM formulations were assessed. Results: F3 formulation gave enhanced entrapment efficiency (EE) (i.e., 50.61%) along with good homogeneity of spherical shaped particle size (PS) (42.58 ± 1.4 nm) with least polydispersity index (PDI) (i.e., 0.193 ± 0.01). The sustained release (up to 24 h) of ginsenoside Rb1 (GRb1) is revealed by the dissolution study of PM. A significantly (p < 0.05) greater anti-oxidant (AO) potential of PM can well be perceived as of the diminution in the lipid peroxidase level in addition to the rise in the glutathione superoxide dismutase (SOD) in addition to catalase levels. It also showed a greater neuroprotective potential exhibiting significant (p < 0.05) augmentation in the nociceptive threshold together with the diminution in damage to nerves. A noteworthy enhancement in the relative BA (157.94%) of GRb1 through the PM formulation can well be seen in the PK studies. Conclusion: It is exhibited that the PM system is an optimistic and feasible strategy to enhance the delivery of GE for the effectual treatment of neuropathic pain.

Keywords: ginseng, neuropathic, phytosome, pain

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Authors: Christine Ysabelle G. Roman, Pauline Torres

Abstract:

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

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

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Authors: Nikolas Aasheim, Laura Sakalauskaitė, Julie Dubois, Malina Ploug Larsen, Paul Michael Petersen, Marcus S. Carstensen, Marcus S. Carstensen, Mai Nguyen, Line Katrine Harder Clemmensen, Kamilla Miskowiak, Klaus Martiny

Abstract:

Background: Major depressive disorder (MDD) is a debilitating condition that affects more than 300 million people worldwide and profoundly impacts well-being and health. Current treatments are based on a trial-and-error approach, and reliable biomarkers are needed for more informed and personalized treatment solutions. One potential biomarker is aberrant gamma-frequency (30-80 Hz) brainwaves, hypothesized to originate from deficiencies in the excitatory-inhibitory interaction between the pyramidal cells and interneurons. An imbalance within this interaction is described as a crucial pathological mechanism in various neuropsychiatric conditions, including MDD, and the modulation of this pathological interaction has been investigated as a potential target. A specific type of steady-state visually evoked potential (SSVEP) in the gamma frequency band, referred to as gamma entrainment using sensory stimuli (GENUS), particularly around the 40Hz spectrum, entrains large scale, fast-spiking PV+ interneurons, facilitating coordinated activity in key brain regions, reduced neuronal and synaptic loss, and enhanced synaptic stability and plasticity. GENUS has shown promise in improving sleep, offering neuroprotective effects in Alzheimer's disease (AD), and reducing pathological markers like Amyloid Beta and TAU proteins, as seen in animal models. In this study, we explore the antidepressant, cognitive, and electrophysiological effects of a novel, non-invasive brain stimulation (NIBS) approach utilizing a 40 Hz invisible spectral flicker to induce gamma activity in patients diagnosed with Major Depressive Disorder (MDD). This non-invasive targeted stimulation of lower gamma band activity (40 Hz) is designed to modulate neural circuits associated with mood and cognitive functions, providing a potential new therapeutic avenue for MDD. Methods and Design: 60 patients with a current diagnosis of a major depressive episode will be enrolled in a randomized, double-blinded, placebo-controlled trial. The active treatment group will receive 40 Hz invisible spectral flickering light stimulation while the control group will receive continuous light matched in colour temperature and brightness. Patients in both groups will get an hour of daily light treatment in their own homes and will attend four follow-up visits to assess depression severity measured by Hamilton Depression Rating Scale (HAM-D₆), several aspects of sleep, cognitive function, quality of life. Additionally, exploratory EEG is conducted to assess spectral changes throughout the protocol. The primary endpoint is the mean change from baseline to week 6 in depression severity (HAM-D₆ subset) between the groups. Current state of affairs/timeline: The FELIX study was initiated in the beginning of 2022, planning to reach stage of publication in December 2025. 21 participants have been enrolled in the protocol thus far, expecting to be finished with trials and recruitment by the end of 2024.

Keywords: major depressive disorder, gamma, neurostimulation, EEG

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Authors: Ying Sun, Biao Cheng, Qing Lu, Xuefei Tao, Xiaoyu Lai, Cheng Guo, Dan Wang

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Fibrinogen-like protein 2 (FGL2) has recently been identified to play an important role in inflammatory diseases such as atherosclerosis through a thrombin-dependent manner. Here, a murine monoclonal antibody was raised against the critical residue Ser(89) of FGL2, and the effects of the anti-FGL2 mAb (SPF89) were analyzed in human umbilical vein endothelial cells (HUVECs) and THP-1 cells. Firstly, it was proved that SPF89, which belongs to the IgG1 subtype with a KD value of 44.5 pM, could specifically show the expression levels of protein FGL2 in different cell lines of known target gene status. The lipopolysaccharide (LPS)-mediated endothelial cell proliferation was significantly inhibited with a decline of phosphorylation nuclear factor-κB (NF-κB) in a dose-dependent manner after SPF89 treatment. Furthermore, SPF89 reduced LPS-induced expression of adhesion molecules and inflammatory cytokines such as vascular cell adhesion molecule-1, tumor necrosis factor-α, Matrix metalloproteinase MMP-2, Integrin αvβ3, and interleukin-6 in HUVECs. In macrophage-like THP-1 cells, SPF89 effectively inhibited LPS and low-density lipoprotein-induced foam cell formation. However, these anti-inflammatory and anti-atherosclerotic effects of anti-FGL2 mAb in HUVECs and THP-1 cells were significantly reduced after treatment with an NF-κB inhibitor PDTC. All the above suggest, by efficiently inhibiting LPS-induced pro-inflammatory effects in vascular endothelial cells by attenuating NF-κB dependent pathway, the new anti-FGL2 mAb SPF89 could to be a potential therapeutic candidate for protecting the vascular endothelium against inflammatory diseases such as atherosclerosis. This work was supported by the Program of Sichuan Science and Technology Department (2017FZ0069) and Collaborative Innovation Program of Sichuan for Elderly Care and Health(YLZBZ1511).

Keywords: monoclonal antibody, fibrinogen like protein 2, inflammation, endothelial cells

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Authors: Panadda Rojpibulstit, Suthathip Kittisenachai, Songchan Puthong, Sirikul Manochantr, Pornpen Gamnarai, Sasichai Kangsadalampai, Sittiruk Roytrakul

Abstract:

Hepatocellular carcinoma (HCC) is the most primary hepatic cancer worldwide. Nowadays a targeted therapy via monoclonal antibodies (mAbs) specific to tumor-associated antigen is continually developed in HCC treatment. In this regard, after establishing and consequently exploring Hep88 mAb’s tumoricidal effect on hepatocellular carcinoma cell line (HepG2 cell line), the Hep88 mAb’s specific Ag from both membrane and cytoplasmic fractions of HepG2 cell line was identified by 2-D gel electrophoresis and western blot analysis. After in-gel digestion and subsequent analysis by liquid chromatography-mass spectrometry (LC-MS), mortalin (HSPA9) and alpha-enolase were identified. The recombinant proteins specific to Hep88 mAb were cloned and expressed in E.coli BL21 (DE3). Moreover, alteration of HepG2 and Chang liver cell line after being induced by Hep88 mAb for 1-3 days was investigated using a transmission electron microscope. The result demonstrated that Hep88 mAb can bind to the recombinant mortalin (HSPA9) andalpha-enolase. In addition, gradual appearance of mitochondria vacuolization and endoplasmic reticulum dilatation were observed. Taken together, paraptosis-like programmed cell death (PCD) of HepG2 is induced by binding of mortalin (HSPA9) and alpha-enolase to Hep88 mAb. Mortalin depletion by formation of Hep88 mAb-mortalin (HSPA9) complex might initiate transcription-independent of p53-mediated apoptosis. Additionally, Hep88 mAb-alpha-enolase complex might initiate HepG2 cells energy exhaustion by glycolysis pathway obstruction. These results imply that Hep88 mAb might be a promising tool for development of an effective treatment of HCC in the next decade.

Keywords: Hepatocellular carcinoma, Monoclonal antibody, Paraptosis-like program cell death, Transmission electron microscopy, mortalin (HSPA9), alpha-enolase

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Authors: Navpreet Kaur, Randhir Singh

Abstract:

Diabetic neuropathy is one of the most common microvascular complications of diabetes mellitus which affects more than 50% of diabetic patients. The present study targeted oxidative stress mediated nerve damage in diabetic rats using a hydro-alcohol extract of Cucurbita pepo L. (Family: Cucurbitaceae) and its potential in treatment of diabetic neuropathy. Diabetes neuropathy was induced in Wistar rats by injection of streptozotocin (65 mg/kg, i.p.) 15 min after Nicotinamide (230 mg/kg, i.p.) administration. Hydro-alcohol extract of C. pepo seeds was assessed by oral administration at 100, 200 and 400 mg/kg in STZ-nicotinamide induced diabetic rats. Thermal hyperalgesia (Eddy's hot plate and tail immersion), mechanical hyperalgesia (Randall-Selitto) and tactile allodynia (Von Frey hair tests) were evaluated in all groups of streptozotocin diabetic rats to assess the extent of neuropathy. Tissue (sciatic nerve) antioxidant enzymes (SOD, CAT, GSH and LPO) levels were measured along with the formation of AGEs in serum to assess the effect of hydro-alcohol extract of C. pepo in ameliorating oxidative stress. Diabetic rats exhibited significantly decreased tail-flick latency in the tail-immersion test and decreased paw withdrawal threshold in both Randall-Selitto and von-Frey hair test. A decrease in the nociceptive threshold was accompanied by significantly increased oxidative stress in sciatic nerve of diabetic rats. Treatment with the C. pepo hydro-alcohol extract significantly attenuated all the behavioral and biochemical alterations in a dose-dependent manner. C. pepo attenuated the diabetic condition and also reversed neuropathic pain through modulation of oxidative stress and thus it may find application as a possible therapeutic agent against diabetic neuropathy.

Keywords: advanced glycation end products, antioxidant enzymes, cucurbita pepo, hyperglycemia

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Authors: Pawan Kumar Gupta, Sumana Ghosh

Abstract:

Parkinson's Disease (PD) is a long-term neurodegenerative movement disorder of the central nervous system with vast symptoms related to the motor system. The common symptoms of PD are tremor, rigidity, bradykinesia/akinesia, and postural instability, but the clinical symptom includes other motor and non‐motor issues. The motor symptoms of the disease are consequence of death of the neurons in a region of the midbrain known as substantia nigra pars compacta, leading to decreased level of a neurotransmitter known as dopamine. The cause of this neuron death is not clearly known but involves formation of Lewy bodies, an abnormal aggregation or clumping of the protein alpha-synuclein in the neurons. Unfortunately, there is no cure for PD, and the management of this disease is challenging. Therefore, it is critical for a patient to be diagnosed at early stages. A limited choice of drugs is available to improve the symptoms, but those become less and less effective over time. Apart from that, with rapid growth in the field of science and technology, other methods such as multi-area brain stimulation are used to treat patients. In order to develop advanced techniques and to support drug development for treating PD patients, an accurate mathematical model is needed to explain the underlying relationship of dopamine secretion in the brain with the hand tremors. There has been a lot of effort in the past few decades on modeling PD tremors and treatment effects from a computational point of view. These models can effectively save time as well as the cost of drug development for the pharmaceutical industry and be helpful for selecting appropriate treatment mechanisms among all possible options. In this review paper, an effort is made to investigate studies on PD modeling and analysis and to highlight some of the key advances in the field over the past centuries with discussion on the current challenges.

Keywords: Parkinson's disease, deep brain stimulation, tremor, modeling

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Authors: Yogesh Kumar, Adarsh Kumar

Abstract:

A body farm is a research facility where research is done on forensic investigation and medico-legal disciplines like forensic entomology, forensic pathology, forensic anthropology, forensic archaeology, and related areas of forensic veterinary. All the research is done to collect data on the rate of decomposition (animal and human) and forensically important insects to assist in crime detection. The data collected is used by forensic pathologists, forensic experts, and other experts for the investigation of crime cases and further research. The research work includes different conditions of a dead body like fresh, bloating, decay, dry, and skeleton, and data on local insects which depends on the climatic conditions of the local areas of that country. Therefore, it is the need of time to collect appropriate data in managed conditions with a proper set-up in every country. Hence, it is the duty of the scientific community of every country to establish/propose such facilities for justice and social management. The body farms are also used for training of police, military, investigative dogs, and other agencies. At present, only four countries viz. U.S., Australia, Canada, and Netherlands have body farms and related facilities in organised manner. There is no body farm in Asia also. In India, we have been trying to establish a body farm in A&N Islands that is near Singapore, Malaysia, and some other Asian countries. In view of the above, it becomes imperative to discuss the matter with Asian countries to collect the data on decomposition in a proper manner by establishing a body farm. We can also share the data, knowledge, and expertise to collaborate with one another to make such facilities better and have good scientific relations to promote science and explore ways of investigation at the world level.

Keywords: body farm, rate of decomposition, forensically important flies, time since death

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Authors: Y. Melis, E. Apicella, E. Dozio, L. Mendolicchio

Abstract:

Introduction: Feeding and Eating Disorders (FED) represent the psychiatric pathology with the highest mortality rate and one of the major disorders with the highest psychiatric and clinical comorbidity. The vagus nerve represents one of the main components of the sympathetic and parasympathetic nervous system and is involved in important neurophysiological functions. In FED, there is a spectrum of symptoms which with TaVNS (Transcutaneous Auricular Vagus Nerve Stimulation) therapy, is possible to have a therapeutic efficacy. Materials and Methods: Sample subjects are composed of 15 female subjects aged > 18 ± 51. Admitted to a psychiatry community having been diagnosed according to DSM-5: anorexia nervosa (AN) (N= 9), bulimia nervosa (BN) (N= 5), binge eating disorder (BED) (N= 1). The protocol included 9 weeks of Ta-VNS stimulation at a frequency of 1.5-3.5 mA for 4 hours per day. The variables detected are the following: Heart Rate Variability (HRV), Hamilton Depression Rating Scale (HAMD-HDRS-17), Body Mass Index (BMI), Beck Anxiety Index (BAI). Results: Data analysis showed statistically significant differences between recording times (p > 0.05) in HAM-D (t0 = 18.28 ± 5.31; t4 = 9.14 ± 7.15), in BAI (t0 = 24.7 ± 10.99; t4 = 13.8 ± 7.0). The reported values show how during (T0-T4) the treatment there is a decay of the degree in the depressive state, in the state of anxiety, and an improvement in the value of BMI. In particular, the BMI in the AN-BN sub-sample had a minimum gain of 5% and a maximum of 11%. The analysis of HRV did not show a clear change among subjects, thus confirming the discordance of the activity of the sympathetic and parasympathetic nervous system in FED. Conclusions: Although the sample does not possess a relevant value to determine long-term efficacy of Ta-VNS or on a larger population, this study reports how the application of neuro-stimulation in FED may become a further approach therapeutic. Indeed, substantial improvements are highlighted in the results and confirmed hypotheses proposed by the study.

Keywords: feeding and eating disorders, neurostimulation, anxiety disorders, depression

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Authors: K. Sahithya, I. Balasundar, Pritapant, T. Raghua

Abstract:

Ni-based superalloy with a nominal composition Ni-14% Cr-11% Co-5.8% Mo-2.4% Ti-2.4% Nb-2.8% Al-0.26 % Fe-0.032% Si-0.069% C (all in wt %) is used as turbine discs in a variety of aero engines. Like any other superalloy, the primary processing of the as-cast superalloy poses a major challenge due to its complex alloy chemistry. The challenge was circumvented by characterizing the different phases present in the material, optimizing the homogenization treatment, identifying a suitable thermomechanical processing window using dynamic materials modeling. The as-cast material was subjected to homogenization at 1200°C for a soaking period of 8 hours and quenched using different media. Water quenching (WQ) after homogenization resulted in very fine spherical γꞌ precipitates of sizes 30-50 nm, whereas furnace cooling (FC) after homogenization resulted in bimodal distribution of precipitates (primary gamma prime of size 300nm and secondary gamma prime of size 5-10 nm). MC type primary carbides that are stable till the melting point of the material were found in both WQ and FC samples. Deformation behaviour of both the materials below (1000-1100°C) and above gamma prime solvus (1100-1175°C) was evaluated by subjecting the material to series of compression tests at different constant true strain rates (0.0001/sec-1/sec). An in-detail examination of the precipitate dislocation interaction mechanisms carried out using TEM revealed precipitate shearing and Orowan looping as the mechanisms governing deformation in WQ and FC, respectively. Incoherent/semi coherent gamma prime precipitates in the case of FC material facilitates better workability of the material, whereas the coherent precipitates in WQ material contributed to higher resistance to deformation of the material. Both the materials exhibited discontinuous dynamic recrystallization (DDRX) above gamma prime solvus temperature. The recrystallization kinetics was slower in the case of WQ material. Very fine grain boundary carbides ( ≤ 300 nm) retarded the recrystallisation kinetics in WQ. Coarse carbides (1-5 µm) facilitate particle stimulated nucleation in FC material. The FC material was cogged (primary hot working) 1120˚C, 0.03/sec resulting in significant grain refinement, i.e., from 3000 μm to 100 μm. The primary processed material was subjected to intensive thermomechanical deformation subsequently by reducing the temperature by 50˚C in each processing step with intermittent heterogenization treatment at selected temperatures aimed at simultaneous coarsening of the gamma prime precipitates and refinement of the gamma matrix grains. The heterogeneous annealing treatment carried out, resulted in gamma grains of 10 μm and gamma prime precipitates of 1-2 μm. Further thermo mechanical processing of the material was carried out at 1025˚C to increase the homogeneity of the obtained micro-duplex structure.

Keywords: superalloys, dynamic material modeling, nickel alloys, dynamic recrystallization, superplasticity

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Authors: Mohammed H. Karim, Bestoon M. Faraj

Abstract:

Introduction: This study aimed to compare the effectiveness of a Dynamic Navigation System (DNS) and a three-dimensional microscope in retrieving broken rotary NiTi files when using trepan burs and the extractor system. Materials and Methods: Thirty maxillary first bicuspids with sixty separate roots were split into two comparable groups based on a comprehensive Cone-Beam Computed Tomography (CBCT) analysis of the root length and curvature. After standardized access opening, glide paths, and patency attainment with the K file (sizes 10 and 15), the teeth were arranged on 3D models (three per quadrant, six per model). Subsequently, controlled-memory heat-treated NiTi rotary files (#25/0.04) were notched 4 mm from the tips and fractured at the apical third of the roots. The C-FR1 Endo file removal system was employed under both guidance to retrieve the fragments, and the success rate, canal aberration, treatment time and volumetric changes were measured. The statistical analysis was performed using IBM SPSS software at a significance level of 0.05. Results: The microscope-guided group had a higher success rate than the DNS guidance, but the difference was insignificant (p > 0.05). In addition, the microscope-guided drills resulted in a substantially lower proportion of canal aberration, required less time to retrieve the fragments and caused minimal change in the root canal volume (p < 0.05). Conclusion: Although dynamically guided trephining with the extractor can retrieve separated instruments, it is inferior to three-dimensional microscope guidance regarding treatment time, procedural errors, and volume change.

Keywords: separated instruments retrieval, dynamic navigation system, 3D video microscope, trephine burs, extractor

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Authors: Asiya Mahtab, Sushama Talegaonkar

Abstract:

The research is aimed at developing targeted lipid-based nanocarrier systems of chondroitin sulfate (CS) to deliver an antirheumatic drug to the inflammatory site in arthritic paw. Lipid-based nanoparticle (TEF-lipo) was prepared by using a thin-film hydration method. The coating of prepared drug-loaded nanoparticles was done by the ionic interaction mechanism. TEF-lipo and CS-coated lipid nanoparticle (CS-lipo) were characterized for mean droplet size, zeta potential, and surface morphology. TEF-lipo and CS-lipo were further subjected to in vitro cell line studies on RAW 264.7 murine macrophage, U937, and MG 63 cell lines. The pharmacodynamic study was performed to establish the effectiveness of the prepared lipid-based conventional and targeted nanoparticles in comparison to pure drugs. Droplet size and zeta potential of TEF-lipo were found to be 128. 92 ± 5.42 nm and +12.6 ± 1.2 mV. It was observed that after the coating of TEF-lipo with CS, particle size increased to 155.6± 2.12 nm and zeta potential changed to -10.2± 1.4mV. Transmission electron microscopic analysis revealed that the nanovesicles were uniformly dispersed and detached from each other. Formulations followed sustained release pattern up to 24 h. Results of cell line studies ind icated that CS-lipo formulation showed the highest cytotoxic potential, thereby proving its enhanced ability to kill the RAW 264.7 murine macrophage and U937 cells when compared with other formulations. It is clear from our in vivo pharmacodynamic results that targeted nanocarriers had a higher inhibitory effect on arthritis progression than nontargeted nanocarriers or free drugs. Results demonstrate that this approach will provide effective treatment for rheumatoid arthritis, and CS served as a potential prophylactic against the advancement of cartilage degeneration.

Keywords: adjuvant induced arthritis, chondroitin sulfate, rheumatoid arthritis, teriflunomide

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Authors: Ilana Singer, Anastasia Lučić, Julie Leclerc

Abstract:

Introduction: Tics, characterized by repetitive, sudden, non-voluntary motor movements or vocalizations, are prevalent in chronic tic disorder (CT) and Tourette Syndrome (TS). These neurodevelopmental disorders often coexist with various psychiatric conditions, leading to challenges and reduced quality of life. While medication in conjunction with behavioral interventions, such as Habit Reversal Training (HRT), Exposure Response Prevention (ERP), and Comprehensive Behavioral Intervention for Tics (CBIT), has shown efficacy, a significant proportion of patients experience persistent tics. Thus, innovative treatment approaches are necessary to improve therapeutic outcomes, such as mindfulness-based approaches. Nonetheless, the effectiveness of mindfulness-based interventions in the context of CT and TS remains understudied. Objective: The objective of this scoping review is to provide an overview of the current state of research on mindfulness-based interventions for CT and TS, identify knowledge and evidence gaps, discuss the effectiveness of mindfulness-based interventions with other treatment options, and discuss implications for clinical practice and policy development. Method: Using guidelines from Peters (2020) and the PRISMA-ScR, a scoping review was conducted. Multiple electronic databases were searched from inception until June 2023, including MEDLINE, EMBASE, PsychInfo, Global Health, PubMed, Web of Science, and Érudit. Inclusion criteria were applied to select relevant studies, and data extraction was independently performed by two reviewers. Results: Five papers were included in the study. Firstly, we found that mindfulness interventions were found to be effective in reducing anxiety and depression while enhancing overall well-being in individuals with tics. Furthermore, the review highlighted the potential role of mindfulness in enhancing functional connectivity within the Default Mode Network (DMN) as a compensatory function in TS patients. This suggests that mindfulness interventions may complement and support traditional therapeutic approaches, particularly HRT, by positively influencing brain networks associated with tic regulation and control. Conclusion: This scoping review contributes to the understanding of the effectiveness of mindfulness-based interventions in managing CT and TS. By identifying research gaps, this review can guide future investigations and interventions to improve outcomes for individuals with CT or TS. Overall, these findings emphasize the potential benefits of incorporating mindfulness-based interventions as a smaller subset within comprehensive treatment strategies. However, it is essential to acknowledge the limitations of this scoping review, such as the exclusion of a pre-established protocol and the limited number of studies available for inclusion. Further research and clinical exploration are necessary to better understand the specific mechanisms and optimal integration of mindfulness-based interventions with existing behavioral interventions for this population.

Keywords: scoping reviews, Tourette Syndrome, tics, mindfulness-based, therapy, intervention

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