Search results for: exposure therapy

Authors: Ilham Aji Dermawan, M. Sapari Dwi Hadian, R. Irvan Sophian, Iyan Haryanto

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The study of the geological structure in the surrounding area of Cidaun, Cianjur Regency, West Java Province, Indonesia was conducted around the southern coast of Java Island. This study aims to determine the potentially structural trap deposits of freshwater resources in the study area, according to that the study area is an area directly adjacent to the beach, where the water around it did not seem fresh and brackish due to the exposure of sea water intrusion. This study uses the method of geomorphological analysis and geological mapping by taking the data directly in the field within 10x10 km of the research area. Geomorphological analysis was done by calculating the watershed drainage density value and roundness of watershed value ratio. The goal is to determine the permeability of the sub-soil conditions, rock constituent, and the flow of surface water. While the field geological mapping aims to take the geological structure data and then will do the reconstruction to determine the geological conditions of research area. The result, from geomorphology aspects, that the considered area of potential groundwater consisted of permeable surface material, permeable sub-soil, and low of water run-off flow. It is very good for groundwater recharge area. While the results of geological reconstruction after conducted of geological mapping is joints that present were initiated for the Cipandak Fault that cuts Cipandak River. That fault across until the Cibako Syncline fold through the Cibako River. This syncline is expected to place of influent groundwater aquifer. The tip of Cibako River then united with Cipandak River, where the Cipandak River extends through Cipandak Syncline fold axis in the southern regions close to its estuary. This syncline is expected to place of influent groundwater aquifer too.

Keywords: geological structure, groundwater, hydrogeology, influent aquifer, structural trap

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Authors: Patricia Jayshree Jacob, Mas Jaffri Masarudinb, Mohd Zobir Hussein, Raha Abdul Rahim

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Iron based ferromagnetic nanoparticles (IONP) and silver nanostructures (AgNP) have found a wide range of application in antimicrobial therapy, cell targeting, and environmental applications. As such, the design of well-defined monodisperse IONPs and AgNPs have become an essential tool in nanotechnology. Fabrication of these nanostructures using conventional methods is not environmentally conducive and weigh heavily on energy and outlays. Selected microorganisms possess the innate ability to reduce metallic ions in colloidal aqueous solution to generate nanoparticles. Hence, harnessing this potential is a way forward in constructing microbial nano-factories, capable of churning out high yields of well-defined IONP’s and AgNP's with physicochemical characteristics on par with the best synthetically produced nanostructures. In this paper, we report the isolation and characterization of bacterial strains isolated from the tropical marine and freshwater ecosystems of Malaysia that demonstrated facile and rapid generation of ferromagnetic nanoparticles and silver nanostructures when precursors such as FeCl₃.6H₂O and AgNO₃ were added to the cell-free bacterial lysate in colloidal solution. Characterization of these nanoparticles was carried out using FESEM, UV Spectrophotometer, XRD, DLS and FTIR. This aerobic bioprocess was carried out at ambient temperature and humidity and has the potential to be developed for environmental friendly, cost effective large scale production of IONP’s. A preliminary bioprocess study on the harvesting time, incubation temperature and pH was also carried out to determine pertinent abiotic parameters contributing to the optimal production of these nanostructures.

Keywords: iron oxide nanoparticles, silver nanoparticles, biosynthesis, aquatic bacteria

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Authors: Naim Izet Kajtazi

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Context: Although rare, glomus tumor (i.e., nonchromaffin chemodectomas and paragan¬gliomas) is the most common middle ear tumor, with female predominance. Pre-operative embolization is often required to devascularize the hypervascular tumor for better surgical outcomes. Process: A 35-year-old female presented with episodes of frequent dizziness, ear fullness, and right ear tinnitus for 12 months. Head imaging revealed a right glomus tympanicum tumor. She underwent pre-operative endovascular embolization of the glomus tympanicum tumor with surgical, cyanoacrylate-based glue. Immediately after the procedure, she developed drowsiness and severe pain in the right temporal region. Further investigations revealed a right cerebellar stroke in the posterior inferior cerebellar artery territory. She was treated with intravenous heparin, followed by one year of oral anticoagulation. With rehabilitation, she significantly recovered from her post embolization stroke. However, the tumor was resected at another institution. Ten years later, follow-up imaging indicated a gradual increase in the size of the glomus jugulare tumor, compressing the nearby critical vascular structures. She subsequently received radiation therapy to treat the residual tumor. Outcome: Currently, she has no neurological deficit, but her mild dizziness, right ear tinnitus, and hearing impairment persist. Relevance: This case highlights the complex nature of these tumors, which often bring challenges to the patients as well as treatment teams. The multi-disciplinary team approach is necessary to tailor the management plan for individual tumors. Although embolization is a safe procedure, careful attention and thoughtful anatomic knowledge regarding dangerous anastomosis are essential to avoid devastating complications. Complications occur due to encountered vessel anomalies and new anastomoses formed during the gluing and changes in hemodynamics.

Keywords: stroke, embolization, MRI brain, cerebral angiogram

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Authors: Sahar Rakhshan, Simonetta Geninatti Crich, Diego Alberti, Rachele Stefania

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The combination of imaging and therapeutic agents in the same smart nanoparticle is a promising option to perform a minimally invasive imaging guided therapy. In this study, Low density lipoproteins (LDL), one of the most attractive biodegradable and biocompatible nanoparticles, were used for the simultaneous delivery of Paclitaxel (PTX), a hydrophobic antitumour drug and an amphiphilic contrast agent, Gd-AAZTA-C17, in B16-F10 melanoma cell line. These cells overexpress LDL receptors, as assessed by Flow cytometry analysis. PTX and Gd-AAZTA-C17 loaded LDLs (LDL-PTX-Gd) have been prepared, characterized and their stability was assessed under 72 h incubation at 37 ◦C and compared to LDL loaded with Gd-AAZTA-C17 (LDL-Gd) and LDL-PTX. The cytotoxic effect of LDL-PTX-Gd was evaluated by MTT assay. The anti-tumour drug loaded into LDLs showed a significantly higher toxicity on B16-F10 cells with respect to the commercially available formulation Paclitaxel Kabi (PTX Kabi) used in clinical applications. It was possible to demonstrate a high uptake of LDL-Gd in B16-F10 cells. As a consequence of the high cell uptake, melanoma cells showed significantly high cytotoxic effect when incubated in the presence of PTX (LDL-PTX-Gd). Furthermore, B16-F10 have been used to perform Magnetic Resonance Imaging. By the analysis of the image signal intensity, it was possible to extrapolate the amount of internalized PTX indirectly by the decrease of relaxation times caused by Gd, proportional to its concentration. Finally, the treatment with PTX loaded LDL on B16-F10 tumour bearing mice resulted in a marked reduction of tumour growth compared to the administration of PTX Kabi alone. In conclusion, LDLs are selectively taken-up by tumour cells and can be successfully exploited for the selective delivery of Paclitaxel and imaging agents.

Keywords: low density lipoprotein, melanoma cell lines, MRI, paclitaxel, personalized medicine application, theragnostic System

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Authors: Hsiao-Chien Tsai, Yu-Pin Chen, Ruei-Ming Chen

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Introduction: Osteoarthritis (OA) is characterized by joint destruction and causes chronic disability. One of the prominent symptoms is pain. Alleviating the pain is necessary and urgent for the therapy of OA patients. However, currently, understanding the mechanisms that drive OA-induced pain remains challenging, which hampers the optimistic management of pain in OA patients. Semaphorin 4D (Sema4D) participates in axon guidance pathway and bone remodeling, thus, may play a role in the regulation of pain in OA. In this study, we have established a rat model of OA to find out the mechanisms of OA-induced pain and to deliberate the roles of Sema4D. Methods: Behavioral changes and the pro-inflammatory cytokines (IL-1β, TNF-α, and IL-17) associated with pain were measured during the development of OA. Sema4D expression in cartilage and synovial membrane at 1, 4, and 12 weeks after inducing OA was analyzed. To assess if Sema4D is related to the neurogenesis in OA as an axon repellant, we analyzed the expression of PGP9.5 as well. Results: Synovitis and cartilage degradation were evident histologically during the development of OA. Mechanical hyperalgesia was most severe at week 1, then persisted thereafter. It was associated with stress coping strategies. Similar to the pain behavioral results, levels of IL-1β and TNF-α in synovial lavage fluid were significantly elevated in the OA group at weeks 1 and 4, respectively. Sema4D expression in cartilage and the synovial membrane was also enhanced in the OA group and was correlated with pain and pro-inflammatory cytokines. The marker of neurogenesis, PGP9.5, was also enhanced during the development of OA. Discussion: OA induced mechanical hyperalgesia, which might be through upregulating IL-1β/TNF-α-mediated Sema4D expressions. If anti-Sema4D treatment could reduce OA-induced mechanical hyperalgesia and prevent the subsequent progression of OA needs to be further investigated. Significance: OA can induce mechanical hyperalgesia through upregulation of IL-1β/TNF-α-mediated Sema4D and PGP9.5 expressions. And the upregulation of Sema4D may indicate the severity or active status of OA and OA-induced pain.

Keywords: traumatic osteoarthritis, mechanical hyperalgesia, Sema4D, inflammatory cytokines

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Authors: Degineh Belachew Andarge, Tariku Lambiyo Anticho, Getamesay Mulatu Jara, Musa Mohammed Ali

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Introduction: Tuberculosis (TB) is a communicable chronic disease causedby Mycobacterium tuberculosis (MTB). About one-third of the world’s population is latently infected with MTB. TB is among the top 10 causes of mortality throughout the globe from a single pathogen. Objective: The aim of this study was to determine the prevalence of tuberculosis,rifampicin-resistant/multidrug-resistant Mycobacterium tuberculosis, and associated factors among presumptive tuberculosis cases attending the tuberculosis clinic of Adare General Hospital located in Hawassa city. Methods: A hospital-based cross-sectional study was conducted among 321 tuberculosis suspected patients from April toJuly 2018. Socio-demographic, environmental, and behavioral data were collected using a structured questionnaire. Sputumspecimens were analyzed using GeneXpert. Data entry was made using Epi info version 7 and analyzed by SPSS version 20. Logistic regression models were used to determine the risk factors. A p-value less than 0.05 was taken as a cut point. Results: In this study, the prevalence of Mycobacterium tuberculosis was 98 (30.5%) with 95% confidence interval (25.5–35.8), and the prevalence of rifampicin-resistant/multidrug-resistantMycobacterium tuberculosis among the 98 Mycobacteriumtuberculosis confirmed cases was 4 (4.1%). The prevalence of rifampicin-resistant/multidrug-resistant Mycobacterium tuberculosisamong the tuberculosis suspected patients was 1.24%. Participants who had a history of treatment with anti-tuberculosisdrugs were more likely to develop rifampicin-resistant/multidrug-resistant Mycobacterium tuberculosis. Conclusions: This study identified relatively high rifampicin-resistant/multidrug-resistant Mycobacterium tuberculosis amongtuberculosis suspected patients in the study area. Early detection of drug-resistant Mycobacterium tuberculosis should be givenenough attention to strengthen the management of tuberculosis cases and improve direct observation therapy short-course and eventually minimize the spread of rifampicin-resistant tuberculosis strain in the community.

Keywords: rifampicin resistance, mycobacterium tuberculosis, risk factors, prevalence of TB

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Authors: Hasan Frookh Jamal

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This is a case of a 36-year-old Bahraini gentleman diagnosed to have Cushing's Syndrome with a large anterior mediastinal mass. He was sent abroad to the Speciality hospital in Jordan, where he underwent diagnostic video-assisted thoracoscopy, partial thymectomy and pericardial fat excision. Histopathology of the mass was reported to be an Atypical carcinoid tumor with a low Ki67 proliferation index of 5%, the mitotic activity of 4 MF/10HPF and pathological stage classification(pTNM): pT1aN1. MRI of the pituitary gland showed an ill-defined non-enhancing focus of about 3mm on the Rt side of the pituitary on coronal images, with a similar but smaller one on the left side, which could be due to enhancing pattern rather than a real lesion as reported. The patient underwent Ga68 Dotate PET/CT scan post-operatively, which showed multiple somatostatin receptor-positive lesions seen within the tail, body and head of the pancreas and positive somatostatin receptor lymph nodes located between the pancreatic head and IVC. There was no uptake detected at the anterior mediastinum nor at the site of thymic mass resection. There was no evidence of any positive somatostatin uptake at the soft tissue or lymph nodes. The patient underwent IPSS, which proved that the source is, in fact, an ectopic source of ACTH secretion. Unfortunately, the patient's serum cortisol remained elevated after surgery and failed to be suppressed by 1 mg ODST and by 2 days LLDST with a high ACTH value. The patient was started on Osilodrostat for treatment of hypercortisolism for the time being and his future treatment plan with Lutetium-177 Dotate therapy vs. bilateral adrenalectomy is to be considered in an MDT meeting.

Keywords: cushing syndrome, neuroendocrine tumur, carcinoid tumor, Thymoma

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Authors: Dativa Maria Aliddeki, Fred Monje, Godfrey Nsereko, Benon Kwesiga, Daniel Kadobera, Alex Riolexus Ario

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Background: Cholera is a severe gastrointestinal disease caused by Vibrio cholera. It has caused several pandemics. On 26 February 2018, a suspected cholera outbreak, with one death, occurred in School X in Hoima Municipality, western Uganda. We investigated to identify the scope and mode of transmission of the outbreak, and recommend evidence-based control measures. Methods: We defined a suspected case as onset of diarrhea, vomiting, or abdominal pain in a student or staff of School X or their family members during 14 February–10 March. A confirmed case was a suspected case with V. cholerae cultured from stool. We reviewed medical records at Hoima Hospital and searched for cases at School X. We conducted descriptive epidemiologic analysis and hypothesis-generating interviews of 15 case-patients. In a retrospective cohort study, we compared attack rates between exposed and unexposed persons. Results: We identified 15 cases among 75 students and staff of School X and their family members (attack rate=20%), with onset from 25-28 February. One patient died (case-fatality rate=6.6%). The epidemic curve indicated a point-source exposure. On 24 February, a student brought fried fish from her home in a fishing village, where a cholera outbreak was ongoing. Of the 21 persons who ate the fish, 57% developed cholera, compared with 5.6% of 54 persons who did not eat (RR=10; 95% CI=3.2-33). None of 4 persons who recooked the fish before eating, compared with 71% of 17 who did not recook it, developed cholera (RR=0.0, 95%CIFisher exact=0.0-0.95). Of 12 stool specimens cultured, 6 yielded V. cholerae. Conclusion: This cholera outbreak was caused by eating fried fish, which might have been contaminated with V. cholerae in a village with an ongoing outbreak. Lack of thorough cooking of the fish might have facilitated the outbreak. We recommended thoroughly cooking fish before consumption.

Keywords: cholera, disease outbreak, foodborne, global health security, Uganda

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Authors: Magdy Abouzeid

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Introduction: Physical activity has been shown to have a positive effect on bone mineral density (BMD) and bone mineral content (BMC) among children, adolescents, and adults. Sports characterized by little or moderate weight bearing or impact have a low osteogenic effect. However, the action of such sports on bone turnover remains unclear. Swimming, as a non-weight-bearing sport, has been considered to be insignificant in the maintenance of bone mass. Purpose: To examine this issue we measured (BMD) and(BMC) of the lumbar spine, proximal femur via dual energy x-ray absorptiometry in the group of elite male swimmers, and determine the effect of swimming training on bone health and compared the results with matched controls group in age, body weight and height. Materials and Methods: Twenty-five male swimmers (age 20.7+/-0.8 years) training for 12-15 hours/week; and the controls group consisted of 25 non-active male (age 21.3 +/-1.3 years) were studied BMD and BMC of lumbar spine, femur were assessed via (DXA) absorptiometry. Results: There was significant difference between swimmers and control group in BMD and BMC, BMD of Swimmers was significantly greater than controls at all sites. The lumbar spine (1, 08 +/-0.202 vs., 0717+0.57 gxcm (-2), right proximal femur (1, 02 +/-, 044 vs., 771+/-, 027 gxcm (-2), and left proximal femur (1.374+/-0.212 vs. 1.01 +/-0.141 gxcm (-2). Swimmers were significantly taller, and had greater BMC and BMD compared to the controls group (P<0.001). Conclusions: These results suggest that swimming training may be beneficial in the prevention or therapy of OSTEOPENIA, and may lead to increased (BMD) and (BMC) for male swimmers. Swimming may be an effective non-pharmacological intervention for the adults and adolescent. Further research with younger athletes of another type of aquatics sport is warranted to better identify the periods of BMD development during which Aquatics sport has the greatest impact on bone health.

Keywords: bone mineral density, lumbar spine, femur, swimming, DXA absorptiometry

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Authors: Qing Li, Maiko Kobayashi, Shigeyoshi Kumeda, Hiroko Ochiai, Toshiya Ochiai, Takashi Miura, Takahide Kagawa, Michiko Imai, Toshiaki Otsuka, Tomoyuki Kawada

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In the present study, we investigated the effects of a forest bathing program on cardiovascular and metabolic parameters. Nineteen healthy male subjects (mean age: 51.3 ± 8.8 years) were selected after obtaining informed consent. These subjects took day trips to a forest park named Akasawa Shizen Kyuyourin, Agematsu, Nagano Prefecture (situated in central Japan), and to an urban area of Nagano Prefecture as a control in August 2015. On both trips, they walked 2.6 km for 80 min each in the morning and afternoon on Saturdays. Blood and urine were sampled in the morning before and after each trip. Cardiovascular and metabolic parameters were measured. Blood pressure and pulse rate were measured by an ambulatory automatic blood pressure monitor. The Japanese version of the profile of mood states (POMS) test was conducted before, during and after the trips. Ambient temperature and humidity were monitoring during the trips. The forest bathing program significantly reduced pulse rate, and significantly increased the score for vigor and decreased the scores for depression, fatigue, and confusion in the POMS test. The levels of urinary noradrenaline and dopamine after forest bathing were significantly lower than those after urban area walking, suggesting the relaxing effect of the forest bathing program. The level of adiponectin in serum after the forest bathing program was significantly greater than that after urban area walking. There was no significant difference in blood pressure between forest and urban area trips during the trips.

Keywords: ambient temperature, blood pressure, forest bathing, forest therapy, human health, POMS, pulse rate

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Authors: Yunjia Yang, Yakun Yan, Peng Li, Gordon Xu, Timothy Mahony, Neena Mitter, Karishma Mody

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Sheep flystrike is one of the most economically important diseases affecting the Australian sheep and wool industry (>356M/annually). Currently, control of Lucillia cuprina relies almost exclusively on chemicals controls and the parasite has developed resistance to nearly all control chemicals used in the past. It is therefore critical to develop an alternative solution for the sustainable control and management of flystrike. RNA interference (RNAi) technologies have been successfully explored in multiple animal industries for developing parasites controls. This research project aims to develop a RNAi based biological control for sheep blowfly. Double-stranded RNA (dsRNA) has already proven successful against viruses, fungi and insects. However, the environmental instability of dsRNA is a major bottleneck with a protection window only lasting 5-7 days. Bentonite polymer (BenPol) technology can overcome this problem, as it can be tuned for controlled release of the dsRNA in the gut challenging pH environment of the blowfly larvae, prolonging its exposure time to and uptake by target cells. We have investigated four different BenPol carriers for their dsRNA loading capabilities of which three of them were able to afford dsRNA stability under multiple temperatures (4°C, 22°C, 40°C, 55°C) in the sheep serum. Based on stability results, we further tested dsRNA from potential targeted genes loaded with BenPol carrier in larvae feeding assay, and get three knockdowns. Our results, establish that the dsRNA when loaded on BenPol particles is stable unlike naked dsRNA which is rapidly degraded in the sheep serum. A stable nanoparticles delivery system that can protect and increase the inherent stability of the dsRNA molecules at higher temperatures in a complex biological fluid like serum, offers a great deal of promise for the future use of this approach for enhancing animal protection.

Keywords: RNA interference, Lucillia cuprina, polymer carriers, polymer stability

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Authors: Evangelia Tsampali, Evangelos Yfantidis, Andreas Ioakim, Maria Stefanidou

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The purpose of this paper is the characterization of the effects of crystalline admixtures on concrete. Crystallites, aided by the presence of humidity, form idiomorphic crystals that block cracks and pores resulting in reduced porosity. In this project, two types of crystallines have been employed. The hydrophilic nature of crystalline admixtures helps the components to react with water and cement particles in the concrete to form calcium silicate hydrates and pore-blocking precipitates in the existing micro-cracks and capillaries. The underlying mechanism relies on the formation of calcium silicate hydrates and the resulting deposits of these crystals become integrally bound with the hydrated cement paste. The crystalline admixtures continue to activate throughout the life of the composite material when in the presence of moisture entering the concrete through hairline cracks, sealing additional gaps. The resulting concrete exhibits significantly increased resistance to water penetration under stress. Admixtures of calcium aluminates can also contribute to this healing mechanism in the same manner. However, this contribution is negligible compared to the calcium silicate hydrates due to the abundance of the latter. These crystalline deposits occur throughout the concrete volume and are a permanent part of the concrete mass. High-performance fibre reinforced cementitious composite (HPFRCC) were produced in the laboratory. The specimens were exposed in three healing conditions: water immersion until testing at 15 °C, sea water immersion until testing at 15 °C, and wet/dry cycles (immersion in tap water for 3 days and drying for 4 days). Specimens were pre-cracked at 28 days, and the achieved cracks width were in the range of 0.10–0.50 mm. Furthermore, microstructure observations and Ultrasonic Pulse Velocity tests have been conducted. Based on the outcomes, self-healing related indicators have also been defined. The results show almost perfect healing capability for specimens healed under seawater, better than for specimens healed in water while inadequate for the wet/dry exposure in both of the crystalline types.

Keywords: autogenous self-healing, concrete, crystalline admixtures, ultrasonic pulse velocity test

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Authors: Morgane Chatard, Clémentine Puech, Nathalie Perek, Frédéric Roche

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Several neurological disorders are linked to repeated hypoxia. The impact of such repeated hypoxic stress, on endothelial cells function of the blood-brain barrier (BBB) is little studied in the literature. Indeed, the study of hypoxic stress in cellular pathways is complex using hypoxia exposure because HIF 1α (factor induced by hypoxia) has a short half life. Our study presents an innovative induction method of repeated hypoxic stress, more reproducible, which allows us to study its impacts on an in vitro contact co-culture BBB model. Repeated hypoxic stress was induced by hydralazine (a mimetic agent of hypoxia pathway) during two hours and repeated during 24 hours. Then, BBB integrity was assessed by permeability measurements (transendothelial electrical resistance and membrane permeability), tight junction protein expressions (cell-ELISA and confocal microscopy) and by studying expression and activity of efflux transporters. First, this study showed that repeated hypoxic stress leads to a BBB’s dysfunction illustrated by a significant increase in permeability. This loss of membrane integrity was linked to a significant decrease of tight junctions’ protein expressions, facilitating a possible transfer of potential cytotoxic compounds in the brain. Secondly, we demonstrated that brain microvascular endothelial cells had set-up defence mechanism. These endothelial cells significantly increased the activity of their efflux transporters which was associated with a significant increase in their expression. In conclusion, repeated hypoxic stress lead to a loss of BBB integrity with a decrease of tight junction proteins. In contrast, endothelial cells increased the expression of their efflux transporters to fight against cytotoxic compounds brain crossing. Unfortunately, enhanced efflux activity could also lead to reducing pharmacological drugs delivering to the brain in such hypoxic conditions.

Keywords: BBB model, efflux transporters, repeated hypoxic stress, tigh junction proteins

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Authors: Mohammed Y. Elsherbeny, Mohamed Salama, Ahmed Lotfy, Hossam Fareed, Nora Mohammed

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Background: Developmental neurotoxicity (DNT) entails the toxic effects imparted by various chemicals on brain during the early childhood when human brains are vulnerable during this period. DNT study in vivo cannot determine the effect of the neurotoxins, as it is not applicable, so using the neurosphere cells of lab animals as an alternative is applicable and time saving. Methods: Cell culture: Rat neural progenitor cells were isolated from rat embryos’ brain. The cortices were aseptically dissected out and the tissues were triturated. The dispersed tissues were allowed to settle. The supernatant was then transferred to a fresh tube and centrifuged. The pellet was placed in Hank’s balanced salt solution and cultured as free-floating neurospheres in proliferation medium. Differentiation was initiated by growth factor withdrawal in differentiation medium and plating onto a poly-d-lysine/ laminin matrix. Chemical Exposure: Neurospheres were treated for 2 weeks with papaverine in proliferation medium. Proliferation analyses: Spheres were cultured. After 0, 4, 5, 11 and 14 days, sphere size was determined by software analyses (CellProfiler, version 2.1; Broad Institute). Diameter of each neurosphere was measured and exported to excel file further to statistical analysis. Viability test: Trypsin-EDTA solution was added to neurospheres to dissociate neurospheres into single cells suspension, then viability evaluated by the Trypan Blue exclusion test. Result: As regards proliferation analysis and percentage of viable cells of papaverin treated groups: There was no significant change in cells proliferation compared to control at 0, 4, 5, 11 and 14 days with concentrations 1, 5 and 10 µM of papaverine, but there is a significant change in cell viability compared to control after 1 week and 2 weeks with the same concentrations of papaverine. Conclusion: Papaverine has toxic effect on viability of neural cell, not on their proliferation, so it may produce focal neural lesions not growth morphological changes.

Keywords: developmental neurotoxicity, neurotoxin, papaverine, neuroshperes

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Authors: Valiollah Babaeipour, Mahdi Rahaie

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food supplements are rich in specific nutrients and bioactive compounds that eliminate free radicals and improve cellular metabolism. The major bioactive compounds are found in bran and cereal sprouts. Secondary metabolites of these microorganisms have antioxidant properties that can be used alone or in combination with chemotherapy and radiation therapy to treat cancer. Biologically active compounds such as benzoquinone derivatives extracted from fermented wheat germ extract (FWGE) have several positive effects on the overall state of human health and strengthen the immune system. The present work describes the discontinuous fermentation of raw wheat germ for FWGE production through the simultaneous culture process using the probiotic strains of Saccharomyces cerevisiae, Lactobacillus plantarum, and the possibility of using solid waste. To increase production efficiency, first to select important factors in the optimization of each fermentation process, using a factorial statistical scheme of stirring fraction (120 to 200 rpm), dilution of solids to solvent (1 to 8-12), fermentation time (16 to 24 hours) and strain to wheat germ ratio (20% to 50%) were studied and then simultaneous culture was performed to increase the yields of 2 and 6 dimethoxybenzoquinone (2,6-DMBQ). Since 2 and 6 dimethoxy benzoquinone were fermented as the main biologically active compound in wheat germ extract, UV-Vis analysis was performed to confirm the presence of 2 and 6 dimethoxy benzoquinone in the final product. In addition, 2,6-DMBQ of some products was isolated in a non-polar C-18 column and quantified using high performance liquid chromatography (HPLC). Based on our findings, it can be concluded that the increase of 2 and 6 dimethoxybenzoquinone in the simultaneous culture of Saccharomyces cerevisiae - Lactobacillus plantarum compared to pure culture of Saccharomyces cerevisiae (from 1.89 mg / g) to 28.9% (2.66 mg / g) Increased.

Keywords: wheat germ, FWGE, saccharomyces cerevisiae, lactobacillus plantarum, co-culture, 2, 6-DMBQ

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Authors: Juan Antonio Mondragon Sanchez, Ruben Santamaria

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The DNA G-quadruplex is a four-stranded DNA structure formed by stacked planes of four base paired guanines (G-quartet). Guanine rich DNA sequences appear in many sites of genomic DNA and can potential form G-quadruplexes, such as those occurring at 3'-terminus of the human telomeric DNA. The formation and stabilization of a G-quadruplex by small ligands at the telomeric region can inhibit the telomerase activity. In turn, the ligands can be used to down regulate oncogene expression making G-quadruplex an attractive target for anticancer therapy. Many G-quadruplex ligands have been proposed with a planar core to facilitate the pi–pi stacking and electrostatic interactions with the G-quartets. However, many drug candidates are impossibilitated to discriminate a G-quadruplex from a double helix DNA structure. In this context, it is important to investigate the site topology for the interaction of a G-quadruplex with a ligand. In this work, we determine the free energy surface of a G-quadruplex-ligand to study the binding modes of the G-quadruplex (TG4T) with the daunomycin (DM) drug. The complex TG4T-DM is studied using classical molecular dynamics in combination with metadynamics simulations. The metadynamics simulations permit an enhanced sampling of the conformational space with a modest computational cost and obtain free energy surfaces in terms of the collective variables (CV). The free energy surfaces of TG4T-DM exhibit other local minima, indicating the presence of additional binding modes of daunomycin that are not observed in short MD simulations without the metadynamics approach. The results are compared with similar calculations on a different structure (the mutated mu-G4T-DM where the 5' thymines on TG4T-DM have been deleted). The results should be of help to design new G-quadruplex drugs, and understand the differences in the recognition topology sites of the duplex and quadruplex DNA structures in their interaction with ligands.

Keywords: g-quadruplex, cancer, molecular dynamics, metadynamics

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Authors: Ounassa Adjroud

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Potassium dichromate (K2Cr2O7) is one of the most toxic elements to which man can be exposed at work or in the environment. The purpose of the current work is to compare the effect of K2Cr2O7 using variations in the dose, route of administration and duration of exposure in male and female Wistar albino rats with a special focus on biochemical parameters. K2Cr2O7 was subcutaneously administered alone (10, 50 and 100 mg/kg body weight) to female Wistar albino rats. Male rats received in their drinking water K2Cr2O7 30 mg/L/day) for 20 consecutive days. The Biochemical parameters were evaluated on days 3, 6 and 21 after subcutaneous (sc.) treatment in female rats and on days 10 and 20 after oral administration in male rats. The subcutaneous (s.c.) administration of 25 mg/kg of K2Cr2O7 to Wistar albino rats induced a slight change in plasma glucose levels during the experiment period. On the contrary, a significant decrease in plasma glucose levels was observed with 50 mg/kg mainly on days 3 (-26%) and 21 (-48%) after treatment compared to controls females rats. On the other hand, the higher dose provoked a significant increase in plasma glucose concentrations on days 6 (+31%) and 21 (+60%). similarly, the lower dose of chromium had no effect on the plasma urea levels. Conversely, a significant increase (122%) in this parameter was obtained during the first three days after treatment. In addition, a significant decrease in plasma glucose levels was observed with 50 mg/kg mainly on days 3 (-26%) and 21 (-48%) after treatment. On the other hand, the higher dose provoked a significant increase in plasma glucose concentrations on days 6 (+31%) and 21 (+60%). similarly, the lower dose of chromium had no effect on the plasma urea levels. Conversely, a significant increase in this parameter (122%) was obtained during the first three days after treatment. In addition, administration of 100 mg/kg of K2Cr2O7 by s.c markedly augmented the levels of plasma urea on days 3 (62%) and 6 (121%). Administration of 30 mg/L/day of K2Cr2O7 in the drinking water induced a significant augmentation in both of plasma glucose (27%) and urea (126%) during the first ten days of treatment. These results suggested that K2Cr2O7 administered subcutaneously or in the drinking water may induce harmful effects on biochemical parameters.

Keywords: glucose, potassium dichromate, Wistar albino rat, urea

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Authors: Dharmendra Jariwala, Robin Christian

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Thermal exposure is a common problem in every manufacturing industry where heat is used in the manufacturing process. In developing countries like India, a lack of awareness regarding the proper work environmental condition is observed among workers. Improper planning of factory building, arrangement of machineries, ventilation system, etc. play a vital role in the rise of temperature within the manufacturing areas. Due to the uncontrolled thermal stress, workers may be subjected to various heat illnesses from mild disorder to heat stroke. Heat stress is responsible for the health risk and reduction in production. Wet Bulb Globe Temperature (WBGT) index and relative humidity are used to evaluate heat stress conditions. WBGT index is a weighted average of natural wet bulb temperature, globe temperature, dry bulb temperature, which are measured with standard instrument QuestTemp 36 area stress monitor. In this study textile processing units have been selected in the industrial estate in the Surat city. Based on the manufacturing process six locations were identified within the plant at which process was undertaken at 120°C to 180°C. These locations were jet dying machine area, stenter machine area, printing machine, looping machine area, washing area which generate process heat. Office area was also selected for comparision purpose as a sixth location. Present Study was conducted in the winter season and summer season for day and night shift. The results shows that average WBGT index was found above Threshold Limiting Value (TLV) during summer season for day and night shift in all three industries except office area. During summer season highest WBGT index of 32.8°C was found during day shift and 31.5°C was found during night shift at printing machine area. Also during winter season highest WBGT index of 30°C and 29.5°C was found at printing machine area during day shift and night shift respectively.

Keywords: relative humidity, textile industry, thermal stress, WBGT

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Authors: Emmanuel Dele Balogun

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This paper analyzes, using descriptive statistics and econometrics data which span the period 1981 to 2014 to gauge the effects of trade policy incentives on economic growth in Nigeria. It argues that the provided incentives penalize economic growth during pre-trade liberalization eras, but stimulated a rapid increase in total factor productivity during the post-liberalization period of 2000 to 2014. The trend analysis shows that Nigeria maintained high tariff walls in economic regulation eras which became low in post liberalization era. The protections were in favor of infant industries, which were mainly appendages of multinationals but against imports of competing food and finished consumer products. The trade openness index confirms the undue exposure of Nigeria’s economy to the vagaries of international market shocks; while banking sector recapitalization and new listing of telecommunications companies deepened the financial markets in post-liberalization era. The structure of economic incentives was biased in favor of construction, trade and services, but against the real sector despite protectionist policies. Total Factor Productivity (TFP) estimates show that the Nigerian economy suffered stagnation in pre-liberalization eras, but experienced rapid growth rates in post-liberalization eras. The regression results relating trade policy incentives to TFP growth rate yielded a significant but negative intercept suggesting that a non-interventionist policy could be detrimental to economic progress, while protective tariff which limits imports of competing products could spur productivity gains in domestic import substitutes beyond factor growth with market liberalization. The main constraint to the effectiveness of trade policy incentives is the failure of benefiting industries to leverage on the domestic factor endowments of the nation. This paper concludes that there is the need to review the current economic transformation strategies urgently with a view to provide policymakers with a better understanding of the most viable options that could make for rapid success.

Keywords: economic growth, macroeconomic incentives, total factor productivity, trade policies

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Authors: Marc Sebastián-Romagosa, Woosang Cho, Rupert Ortner, Christy Li, Christoph Guger

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Neurorehabilitation based on Brain-Computer Interfaces (BCIs) shows important rehabilitation effects for patients after stroke. Previous studies have shown improvements for patients that are in a chronic stage and/or have severe hemiparesis and are particularly challenging for conventional rehabilitation techniques. For this publication, seven stroke patients in the chronic phase with hemiparesis in the lower extremity were recruited. All of them participated in 25 BCI sessions about 3 times a week. The BCI system was based on the Motor Imagery (MI) of the paretic ankle dorsiflexion and healthy wrist dorsiflexion with Functional Electrical Stimulation (FES) and avatar feedback. Assessments were conducted to assess the changes in motor improvement before, after and during the rehabilitation training. Our primary measures used for the assessment were the 10-meters walking test (10MWT), Range of Motion (ROM) of the ankle dorsiflexion and Timed Up and Go (TUG). Results show a significant increase in the gait speed in the primary measure 10MWT fast velocity of 0.18 m/s IQR = [0.12 to 0.2], P = 0.016. The speed in the TUG was also significantly increased by 0.1 m/s IQR = [0.09 to 0.11], P = 0.031. The active ROM assessment increased 4.65º, and IQR = [ 1.67 - 7.4], after rehabilitation training, P = 0.029. These functional improvements persisted at least one month after the end of the therapy. These outcomes show the feasibility of this BCI approach for chronic stroke patients and further support the growing consensus that these types of tools might develop into a new paradigm for rehabilitation tools for stroke patients. However, the results are from only seven chronic stroke patients, so the authors believe that this approach should be further validated in broader randomized controlled studies involving more patients. MI and FES-based non-invasive BCIs are showing improvement in the gait rehabilitation of patients in the chronic stage after stroke. This could have an impact on the rehabilitation techniques used for these patients, especially when they are severely impaired and their mobility is limited.

Keywords: neuroscience, brain computer interfaces, rehabilitat, stroke

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Authors: S. Belakry, D. Fasquelle, A. Rolle, E. Capoen, R. N. Vannier, J. C. Carru

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Solid oxide fuel cells (SOFCs) are promising devices for energy conversion due to their high electrical efficiency and eco-friendly behavior. Their performance is not only influenced by the microstructural and electrical properties of the electrodes and electrolyte but also depends on the interactions at the interfaces. Nowadays, commercial SOFCs are electrically efficient at high operating temperatures, typically between 800 and 1000 °C, which restricts their real-life applications. The present work deals with the objectives to reduce the operating temperature and to develop cost-effective intermediate-temperature solid oxide fuel cells (IT-SOFCs). This work focuses on the development of metal-supported solid oxide fuel cells (MS-IT-SOFCs) that would provide cheaper SOFC cells with increased lifetime and reduced operating temperature. In the framework, the local company TIBTECH brings its skills for the manufacturing of porous metal supports. This part of the work focuses on the physical, chemical, and electrical characterizations of porous metallic supports (stainless steel 316 L and FeCrAl alloy) under different exposure conditions of temperature and atmosphere by studying oxidation, mechanical resistance, and electrical conductivity of the materials. Within the target operating temperature (i.e., 500 to 700 ° C), the stainless steel 316 L and FeCrAl alloy slightly oxidize in the air and H2, but don’t deform; whereas under Ar atmosphere, they oxidize more than with previously mentioned atmospheres. Above 700 °C under air and Ar, the two metallic supports undergo high oxidation. From 500 to 700 °C, the resistivity of FeCrAl increases by 55%. But nevertheless, the FeCrAl resistivity increases more slowly than the stainless steel 316L resistivity. This study allows us to verify the compatibility of electrodes and electrolyte materials with metallic support at the operating requirements of the IT-SOFC cell. The characterizations made in this context will also allow us to choose the most suitable fabrication process for all functional layers in order to limit the oxidation of the metallic supports.

Keywords: stainless steel 316L, FeCrAl alloy, solid oxide fuel cells, porous metallic support

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Authors: Zahra Kazemi Saleh, Bénédicte Poulin-Charronnat, Annie Vinter

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This study examines the effects of aging on visual statistical learning, using eye-tracking techniques to investigate this cognitive phenomenon. Visual statistical learning is a fundamental brain function that enables the automatic and implicit recognition, processing, and internalization of environmental patterns over time. Some previous research has suggested the robustness of this learning mechanism throughout the aging process, underscoring its importance in the context of education and rehabilitation for the elderly. The study included three distinct groups of participants, including 21 young adults (Mage: 19.73), 20 young-old adults (Mage: 67.22), and 17 old-old adults (Mage: 79.34). Participants were exposed to a series of 12 arbitrary black shapes organized into 6 pairs, each with different spatial configurations and orientations (horizontal, vertical, and oblique). These pairs were not explicitly revealed to the participants, who were instructed to passively observe 144 grids presented sequentially on the screen for a total duration of 7 min. In the subsequent test phase, participants performed a two-alternative forced-choice task in which they had to identify the most familiar pair from 48 trials, each consisting of a base pair and a non-base pair. Behavioral analysis using t-tests revealed notable findings. The mean score for the first group was significantly above chance, indicating the presence of visual statistical learning. Similarly, the second group also performed significantly above chance, confirming the persistence of visual statistical learning in young-old adults. Conversely, the third group, consisting of old-old adults, showed a mean score that was not significantly above chance. This lack of statistical learning in the old-old adult group suggests a decline in this cognitive ability with age. Preliminary eye-tracking results showed a decrease in the number and duration of fixations during the exposure phase for all groups. The main difference was that older participants focused more often on empty cases than younger participants, likely due to a decline in the ability to ignore irrelevant information, resulting in a decrease in statistical learning performance.

Keywords: aging, eye tracking, implicit learning, visual statistical learning

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Authors: Naso Isaiah Thanavisuth

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Introduction: Medical cannabis can be used for treatment, including anorexia, pain, inflammation, multiple sclerosis, Parkinson's disease, epilepsy, cancer, and metabolic syndrome-related disorders. However, medical cannabis leads to adverse effects (AEs), which is delta-9-tetrahydrocannabinol (THC). In previous studies, the major of THC metabolism enzymes are CYP2C9. Especially, the variation of CYP2C9 gene consist of CYP2C9*2 on exon 3 (C430T) (Arg144Cys) and CYP2C9*3 on exon 7 (A1075C) (Ile359Leu) to decrease enzyme activity. Notwithstanding, there is no data describing whether the variant of CYP2C9 genes are a pharmacogenetics marker for prediction of THC-induced AEs in Thai patients. Objective: We want to investigate the association between CYP2C9 gene and THC-induced AEs in Thai patients. Method: We enrolled 39 Thai patients with medical cannabis treatment consisting of men and women who were classified by clinical data. The quality of DNA extraction was assessed by using NanoDrop ND-1000. The CYP2C9*2 and *3 genotyping were conducted using the TaqMan real time PCR assay (ABI, Foster City, CA, USA). Results: All Thai patients who received the medical cannabis consist of twenty four (61.54%) patients who were female and fifteen (38.46%) were male, with age range 27- 87 years. Moreover, the most AEs in Thai patients who were treated with medical cannabis between cases and controls were tachycardia, arrhythmia, dry mouth, and nausea. Particularly, thirteen (72.22%) medical cannabis-induced AEs were female and age range 33 – 69 years. In this study, none of the medical cannabis groups carried CYP2C9*2 variants in Thai patients. The CYP2C9*3 variants (*1/*3, intermediate metabolizer, IM) and (*3/*3, poor metabolizer, PM) were found, three of thirty nine (7.69%) and one of thirty nine (2.56%) , respectively. Conclusion: This is the first study to confirm the genetic polymorphism of CYP2C9 and medical cannabis-induced AEs in the Thai population. Although, our results indicates that there is no found the CYP2C9*2. However, the variation of CYP2C9 allele might serve as a pharmacogenetics marker for screening before initiating the therapy with medical cannabis for prevention of medical cannabis-induced AEs.

Keywords: CYP2C9, medical cannabis, adverse effects, THC, P450

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Authors: Carolina S. Monteiro, Eugénia Pinto, Miguel A. Faria, Sara C. Cunha

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About half of the world's population eats rice daily, making it the primary food source for billions of people. Besides its nutrition potential, rice can be a significant route of exposure to many contaminants. Mycotoxins are an example of such contaminants that can be present in rice. Among them, ochratoxin (OTA), citrinin (CIT), and zearalenone (ZEN) are frequently reported in rice. During digestion, only a fraction of mycotoxins from food can be absorbed (bioaccessible fraction), influencing their ability to cause toxic effects. Insufficient knowledge of the bioavailability of mycotoxins, alone and in combination, may hinder an accurate risk assessment of contaminants ingested by humans. In this context, two different rice (Oryza sativa) varieties, Carolino white and Carolino brown, both with and without turmeric, were boiled and individually spiked with OTA, CIT, and ZEN plus with its combination. Subsequently, samples were submitted to the INFOGEST harmonized in vitro digestion protocol to evaluate the bioaccessibility of mycotoxins. Afterward, the in vitro intestinal transport of the mycotoxins, both alone and in combination, was evaluated in digests of Carolino white rice with and without turmeric. Assays were performed with a monolayers of of Caco-2 and HT-29 cells. Bioaccessibility of OTA and ZEN, alone and in combination, were similar in Carolino white and brown rice with or without turmeric. For CIT, when Carolino white rice was used, the bioaccessibility was higher alone than in combination (62.00% vs. 25.00%, without turmeric; 87.56% vs. 53.87%, with turmeric); however, with Carolino brown rice was the opposite (66.38% vs. 75.20%, without turmeric; 43.89% vs. 59.44%, with turmeric). All the mycotoxins, isolated, reached the higher bioaccessibility in the Carolino white rice with turmeric (CIT: 87.56%; OTA: 59.24%; ZEN: 58.05%). When mycotoxins are co-present, the higher bioaccessibility of each one varies with the type of rice. In general, when turmeric is present, bioaccessibility increases, except for CIT, using Carolino brown rice. Concerning the intestinal absorption in vitro, after 3 hours of transport, all mycotoxins were detected in the basolateral compartment being thus transported through the cells monolayer. ZEN presented the highest fraction absorbed isolated and combined, followed by CIT and OTA. These findings highlight that the presence of other components in the complex dietary matrix, like turmeric, and the co-presence of mycotoxins can affect its final bioavailability with obvious implications for health risk. This work provides new insights to qualitatively and quantitatively describe mycotoxin in rice fate during human digestion and intestinal absorption and further contribute to better risk assessment.

Keywords: bioaccessibility, digestion, intestinal absorption, mycotoxins

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Authors: B. González-Yebra, B. Flores-Nieto, P. Aguilar-Salinas, M. Preciado Puga, A. L. González Yebra

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The monitoring of populations occupationally exposed to organic solvents has been an important issue for several shoe factories for years since the International Agency for Research on Cancer (IARC) has advised on the potential carcinogenic risk of chemicals related to occupations. In order to detect if exposition to organic solvents used in some Mexican shoe factories contributes to oral carcinogenesis, we performed monitoring in three factories. Occupational exposure was determined by using monitors 3M. Organic solvents were assessed by gas chromatography. Then, we recruited 30 shoe workers (30.2 ± 8.4 years) and 10 unexposed subjects (43.3 ± 11.2 years) for the micronuclei (MN) test and immunodetection of some cancer biomarkers (ki-67, p16, caspase-3) in scraped oral epithelial cells. Monitored solvents detected were acetone, benzene, hexane, methyl ethyl ketone, and toluene in acceptable levels according to Official Mexican Norm. We found by MN test higher incidence of nuclear abnormalities (karyorrhexis, pycnosis, karyolysis, condensed chromatin, and macronuclei) in the exposed group than the non-exposed group. On the other hand, we found, a negative expression for Ki-67 and p16 in exfoliated epithelial cells from exposed and non-exposed to organic solvents subjects. Only caspase-3 shown positive patter of expression in 9/30 (30%) exposed subjects, and we detected high karyolysis incidence in caspase-3 subjects (p = 0.021). The absence of expression of proliferation markers p16 and ki-67 and presence of apoptosis marker caspase-3 are indicating the absence of malignancy in oral epithelial cells and low risk for oral cancer. It is a fact that the MN test is a very effective method to detect nuclear abnormalities in exfoliated buccal cells from subjects that have been exposed to organic solvents in the shoe industry. However, in order to improve this tool and predict cancer risk is it is mandatory to implement complementary tests as other biomarkers that can help to detect malignancy in individuals occupationally exposed.

Keywords: biomarkers, oral cancer, organic solvents, shoe industries

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Authors: Anupam Chanda

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Presently Packaging plays a significant role for drug discoveries. The process of selecting materials and the type of packaging also offers an opportunity for the Packaging scientist to look for biological delivery choices. Most injectable protein products were supplied in some sort of glass vial, prefilled syringe, cartridge. Those product having high Ph content there is a chance of “delamination “from inner surface of glass vial. With protein-based drugs, the biggest issue is the effect of packaging derivatives on the protein’s threedimensional and surface structure. These are any effects that relate to denaturation or aggregation of the protein due to oxidation or interactions from contaminants or impurities in the preparation. The potential for these effects needs to be carefully considered in choosing the container and the container closure system to avoid putting patients in jeopardy. Cause of Delamination : -Formulations with a high pH include phosphate and citrate buffers increase the risk of glass delamination. -High alkali content in glass could accelerate erosion. -High temperature during the vial-forming process increase the risk of glass delamination. -Terminal sterilization (irradiated at 20-40 kGy for 150 min) also is a risk factor for specific products(veterinary parenteral administration),could cause delamination. -High product-storage temperatures and long exposure times can increase the rate and severity of glass delamination. How to prevent Delamination -Treating the surface of the glass vials with materials, such as ammonium sulfate or siliconization can reduce the rate of glass erosion. -Consider alternative sterilization methods only in rare cases. -The correct specification for the glass to ensure its suitability for the pH of the product. -Use Cyclic olefin copolymer(COC)/Cyclic olefin Polymer(COP) Adsorption of protein and Solutions: Option#1 Coat with linear methoxylated polyglycerol and hyperbranchedmethoxylated polyglycerol. Option#2 Thehyperbranched non-methoxylated coating performed best. Option#3 Coat with hyperbranched polyglycerol Option#4 Right selection of Sterilization of glass vial/syringe.

Keywords: delamination of glass, ptrotien adoptions inside the glass surface, extractable & leachable solutions, injectable designs for new drugs

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Authors: E. Syngelaki, C. C. F. Schinkel, S. Klatt, E. Hörandl

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Environmental influence can alter the conditions for plant development and can trigger changes in epigenetic variation. Thus, the exposure to abiotic environmental stress can lead to different DNA methylation profiles and may have evolutionary consequences for adaptation. Epigenetic control mechanisms may further influence mode of reproduction. The alpine species R. kuepferi has diploid and tetraploid cytotypes, that are mostly sexual and facultative apomicts, respectively. Hence, it is a suitable model system for studying the correlations of mode of reproduction, ploidy, and environmental stress. Diploid and tetraploid individuals were placed in two climate chambers and treated with low (+7°C day/+2°C night, -1°C cold shocks for three nights per week) and warm (control) temperatures (+15°C day/+10°C night). Subsequently, methylation sensitive-Amplified Fragment-Length Polymorphism (AFPL) markers were used to screen genome-wide methylation alterations triggered by stress treatments. The dataset was analyzed for four groups regarding treatment (cold/warm) and ploidy level (diploid/tetraploid), and also separately for full methylated, hemi-methylated and unmethylated sites. Patterns of epigenetic variation suggested that diploids differed significantly in their profiles from tetraploids independent from treatment, while treatments did not differ significantly within cytotypes. Furthermore, diploids are more differentiated than the tetraploids in overall methylation profiles of both treatments. This observation is in accordance with the increased frequency of apomictic seed formation in diploids and maintenance of facultative apomixis in tetraploids during the experiment. Global analysis of molecular variance showed higher epigenetic variation within groups than among them, while locus-by-locus analysis of molecular variance showed a high number (54.7%) of significantly differentiated un-methylated loci. To summarise, epigenetic variation seems to depend on ploidy level, and in diploids may be correlated to changes in mode of reproduction. However, further studies are needed to elucidate the mechanism and possible functional significance of these correlations.

Keywords: apomixis, cold stress, DNA methylation, Ranunculus kuepferi

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Authors: Masaaki Ii, Takashi Saito, Yasuhiko Tabata, Shintaro Nemoto

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Background: Clinical trials of autologous adipose-derived stem cell (AdSC) therapy for ischemic heart diseases (IHD) are now on-going. We have investigated the hypothesis that combination of AdSCs and statin, an agent with pleiotropic effects, could augment the therapeutic effect on myocardial infarction (MI). Methods and Results: Human AdSC functions with different doses of simvastatin-conjugated nanoparticle (STNP) uptake were evaluated by in vitro assays. STNP promoted the migration activity without changing the proliferation activity, and also up-regulated growth factors. Next, MI was induced by LAD ligation in nude mice, and the mice were assigned in the following groups 3 days after MI: 1) PBS (control), 2) NP-AdSCs (50000 cells), 3) STNP, and 4) STNP-AdSCs (50000 cells). Cardiac functional recovery assessed by echocardiography was improved at 4 weeks after surgery in STNP-AdSC group. Masson’s trichrome-stained sections revealed that LV fibrosis length was reduced, and the number of TUNEL-positive cardiomyocytes was less in STNP-AdSC group. Surprisingly, a number of de novo endogenous Nkx-2.5/GATA4 positive immature cardiomyocytes as well as massive vascular formation were observed in outer layer of infarcted myocardium despite of a few recruited/retained transfused STNP-AdSCs 4 weeks after MI in STNP-AdSC group. Finally, massive myocardial regeneration was observed 8 weeks after MI. Conclusions: Intravenously injected small number of statin nanoparticle-loaded hAdSCs exhibited a potent therapeutic effect inducing endogenous cardiac tissue regeneration.

Keywords: statin, drug delivery system, stem cells, cardiac regeneration

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Authors: Tanyaporn Chairoch

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Introduction: Cannabis is a drug to treat patients with many diseases such as Multiple sclerosis, Alzheimer’s disease, and Epilepsy, where theycontain many active compounds such as delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Especially, THC is the primary psychoactive ingredient in cannabis and binds to cannabinoid 1 (CB1) receptors. Moreover, CB1 is located on the neocortex, hippocampus, basal ganglia, cerebellum, and brainstem. In previous study, we found the association between the variant of CB1recptors gene (rs2023239) and decreased effect of nicotine reinforcement in patients. However, there are no data describing whether the distribution of CB1 receptor gene is a genetic marker for Thai patients who are treated with cannabis. Objective: Thus, the aim of this study we want to investigate the frequency of the CB1 receptor gene in Thai patients. Materials and Methods: All of sixty Thai patients received the medical cannabis for treatment who were recruited in this study. DNA will be extracted from EDTA whole blood by Genomic DNA Mini Kit. The genotyping of CNR1 gene (rs 2023239) was genotyped by the TaqMan real time PCR assay (ABI, Foster City, CA, USA).and using the real-time PCR ViiA7 (ABI, Foster City, CA, USA). Results: We found thirty-eight (63.3%) Thai patients were female, and twenty-two (36.70%) were male in this study with median age of 45.8 (range19 – 87 ) years. Especially, thirty-two (53.30%) medical cannabis tolerant controls were female ( 55%) and median age of52.1 (range 27 – 79 ) years. The most adverse effects for medical cannabis treatment was tachycardia. Furthermore, the number of rs 2023239 (TT) carriers was 26 of 27 (96.29%) in medical cannabis-induced adverse effects and 32 of 33 (96.96%) in tolerant controls. Additionally, rs 2023239 (CT) variant was found just only one of twenty-seven (3.7%) in medical cannabis-induced adverse effects and 1 of 33 (3.03%) in tolerant controls. Conclusions: The distribution of genetic variant in CNR1 gene might serve as a pharmacogenetics markers for screening before initiating the therapy with medical cannabis in Thai patients.

Keywords: cannabis, pharmacogenetics, CNR1 gene, thai patient

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Authors: Ammar Asma, Bouafia Nabiha, Ghammam Rim, Ezzi Olfa, Ben Cheikh Asma, Mahjoub Mohamed, Helali Radhia, Sma Nesrine, Chouchène Imed, Boussarsar Hamadi, Njah Mansour

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Background: Central venous catheter associated infections (CVC-AI) are among the serious hospital-acquired infections. The aims of this study are to determine the incidence of CVC-AI, and their risk factors among patients followed in a Tunisian medical intensive care unit (ICU). Materials / Methods: A prospective cohort study conducted between September 15th, 2015 and November 15th, 2016 in an 8-bed medical ICU including all patients admitted for more than 48h. CVC-AI were defined according to CDC of ATLANTA criteria. The enrollment was based on clinical and laboratory diagnosis of CVC-AI. For all subjects, age, sex, underlying diseases, SAPS II score, ICU length of stay, exposure to CVC (number of CVC placed, site of insertion and duration catheterization) were recorded. Risk factors were analyzed by conditional stepwise logistic regression. The p-value of < 0.05 was considered significant. Results: Among 192 eligible patients, 144 patients (75%) had a central venous catheter. Twenty-eight patients (19.4%) had developed CVC-AI with density rate incidence 20.02/1000 CVC-days. Among these infections, 60.7% (n=17) were systemic CVC-AI (with negative blood culture), and 35.7% (n=10) were bloodstream CVC-AI. The mean SAPS II of patients with CVC-AI was 32.76 14.48; their mean Charlson index was 1.77 1.55, their mean duration of catheterization was 15.46 10.81 days and the mean duration of one central line was 5.8+/-3.72 days. Gram-negative bacteria was determined in 53.5 % of CVC-AI (n= 15) dominated by multi-drug resistant Acinetobacter baumani (n=7). Staphylococci were isolated in 3 CVC-AI. Fourteen (50%) patients with CVC-AI died. Univariate analysis identified men (p=0.034), the referral from another hospital department (p=0.03), tobacco (p=0.006), duration of sedation (p=0.003) and the duration of catheterization (p=0), as possible risk factors of CVC-AI. Multivariate analysis showed that independent factors of CVC-AI were, male sex; OR= 5.73, IC 95% [2; 16.46], p=0.001, Ramsay score; OR= 1.57, IC 95% [1.036; 2.38], p=0.033, and duration of catheterization; OR=1.093, IC 95% [1.035; 1.15], p=0.001. Conclusion: In a monocenter cohort, CVC-AI had a high density and is associated with poor outcome. Identifying the risk factors is necessary to find solutions for this major health problem.

Keywords: central venous catheter associated infection, intensive care unit, prospective cohort studies, risk factors

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