Search results for: self-regulation couple therapy

Authors: Tadesse Melaku Abegaz, Akshaya Srikanth Bahagavathula, Abdulla Shehab Sheab, Asim Hassen

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Objectives: Non-adherence and discontinuation of anticoagulant therapy lead to increased ischemic stroke risk and contributes to suboptimal outcomes of the anticoagulant treatment. This systematic review and meta-analysis were aimed to investigate the adherence to NOACs and adverse events in patients with AF. Methods: Original research articles conducted on patients with AF and using any NOACs (dabigatran, rivoraxaban and apixaban) reporting adherence for at least 35 days were included. Scientific databases including PubMed, Web of Science, and Google Scholar were searched using MeSH keywords to obtaining literature researched between 2008 to till June, 2016. Study characteristics, patient’s sociodemographic and clinical characteristics, medication adherence levels and bleeding events reported were recorded. Results: The overall sample size of the six studies is 1,640,157, with CHADS2 scores < 2 in 551 patients, CHADS2-VASc ≥ 2 in 62,232 AF patients. Three-forth [75.6% (95%CI= 66.5-84.8), p < 0.001] are adherent to NOACs. However, a higher rate [72.7% (62.5-82.9), p < 0.001] of adherence was observed with Dabigatran than Apixaban [59.9% (3.2-123.1), p=0.063] and Rivaroxaban [59.3% (38.7-80.0), p<0.001]. Sub-group analysis revealed that nearly 57% of the AF patients on NOACs have CHADS2 scores < 2 and 20% of these patients were non-adherent to NOACs. Overall bleeding events rate associated with NOACs non-adherent AF patients was found to be 7.5% (0.2-14.8), p=0.045. However, nearly 11.2% of AF patients experienced bleeding events were non-adherent to NOAC medications. A higher proportion of bleeding events were noticed with Dabigatran (14.7%). Conclusions: Adherence rates, while uniformly suboptimal, nevertheless varied considerably, lowest at 59.3% for rivaroxaban and 59.9% for apixaban, followed by dabigatran (75.6%). Overall bleeding events associated with NOACs rates were 7.5%. However, lower adherence to NOACs was associated with worse outcomes among patients with greater stroke risk.

Keywords: atrial fibrillation, bleeding events, meta-analysis, novel oral anticoagulants

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Authors: Nahid Eskandari, Marjan Ghagozolo, Ehsan Almasi

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Introduction: Silymarin, as a polyphenolic flavonoid derived from milk thistle (Silybum marianum), is known to have antioxidant, immunomodulatory, antiproliferative, antifibrotic, and antiviral effects. The goal of this study was to determine immunosuppressive effect of Silymarin on proliferation and apoptosis of human T cells in comparison with Rapamycin and FK506. Methods: Peripheral Blood Mononuclear Cells (PBMCs) from healthy individuals were activated with Con A (5µg/ml) and then treated with Silymarin, Rapamycin and FK506 in various concentrations (0.001, 0.01, 0.1, 1, 10,100 and 200M) for 5 days. PBMCs were examined for proliferation using CFSE assay and the concentration that inhibited 50% of the cell proliferation (IC50) was determined for each treatment. For apoptosis assay using flow cytometry, PBMCs were activated with Con A and treated with IC50 dose of Silymarin, Rapamycin and FK506 for 5 days, then cell apoptosis was analysed by FITC-annexin V/PI staining and flow cytometry. The effects of Silymarin, Rapamycin and FK506 on the activation of PARP (poly ADP ribose polymerase) pathway in PBMCs stimulated with Con A and treated with IC50 dose of drugs for 5 days evaluated using the PathScan cleaved PARP sandwich ELISA kit. Results: This study showed that Silymarin had the ability to inhibit T cell proliferation in vitro. Moreover, our results indicated that 100 μM (P < 0.001) and 200 μM (P < 0.001) of Silymarin has more inhibitory effect on T cells proliferation than FK506 and Rapamycin. Our data showed that the effective doses (IC50) of Silymarin, FK506 and Rapamycin were 3×10-5 µM, 10-8 µM and 10-6 µM respectively. Data showed that the inhibitory effect of Silymarin, FK506 and Rapamycin on T cell proliferation was not due to cytotoxicity and none of these drugs at IC50 concentration had not affected the level of cleaved PARP. Conclusion: Silymarin could be a good candidate for immunosuppressive therapy for certain medical conditions with superior efficacy and lesser toxicity in comparison with other immunosuppressive drugs.

Keywords: silymarin, immunosuppressive effect, rapamycin, immunology

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Authors: Kevin V. Bui, Richard A. Claytor, Elizabeth M. Priolo, Weihui Li

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Oxygen deprivation masks operate through the use of restricting valves as a means to reduce respiratory flow where flow is inversely proportional to the resistance applied. This produces the same effect as higher altitudes where lower pressure leads to reduced respiratory flow. Both increased resistance with restricting valves and reduce the pressure of higher altitudes make breathing difficultier and force breathing muscles (diaphragm and intercostal muscles) working harder. The process exercises these muscles, improves their strength and results in overall better breathing efficiency. Currently, these oxygen deprivation masks are purely mechanical devices without any electronic sensor to monitor the breathing condition, thus not be able to provide feedback on the breathing effort nor to evaluate the lung function. That is part of the reason that these masks are mainly used for high-level athletes to mimic training in higher altitude conditions, not suitable for patients or customers. The design aims to improve the current method of oxygen deprivation mask to include a larger scope of patients and customers while providing quantitative biometric data that the current design lacks. This will be accomplished by integrating sensors into the mask’s breathing valves along with data acquisition and Bluetooth modules for signal processing and transmission. Early stages of the sensor mask will measure breathing rate as a function of changing the air pressure in the mask, with later iterations providing feedback on flow rate. Data regarding breathing rate will be prudent in determining whether training or therapy is improving breathing function and quantify this improvement.

Keywords: oxygen deprivation mask, lung function, spirometer, Bluetooth

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Authors: A. Van Staden, N. Purcell

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Spelling development is complex and multifaceted and relies on several cognitive-linguistic processes. This paper explored the spelling difficulties of English second language learners with auditory processing delays. This empirical study aims to address these issues by means of an intervention design. Specifically, the objectives are: (a) to develop and implement a multi-sensory spelling program for second language learners with auditory processing difficulties (APD) for a period of 6 months; (b) to assess the efficacy of the multi-sensory spelling program and whether this intervention could significantly improve experimental learners' spelling, phonological awareness, and processing (PA), rapid automatized naming (RAN), working memory (WM), word reading and reading comprehension; and (c) to determine the relationship (or interplay) between these cognitive and linguistic skills (mentioned above), and how they influence spelling development. Forty-four English, second language learners with APD were sampled from one primary school in the Free State province. The learners were randomly assigned to either an experimental (n=22) or control group (n=22). During the implementation of the spelling program, several visual, tactile and kinesthetic exercises, including the utilization of fingerspelling were introduced to support the experimental learners’ (N = 22) spelling development. Post-test results showed the efficacy of the multi-sensory spelling program, with the experimental group who were trained in utilising multi-sensory coding and fingerspelling outperforming learners from the control group on the cognitive-linguistic, spelling and reading measures. The results and efficacy of this multi-sensory spelling program and the utilisation of fingerspelling for hearing second language learners with APD open up innovative perspectives for the prevention and targeted remediation of spelling difficulties.

Keywords: English second language spellers, auditory processing delays, spelling difficulties, multi-sensory intervention program

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Authors: Nehal Adel Khalil, Amel Foad Ketat, Fairouz Elsayed Mohamed Ali, Nahla Abdelmoneim Hamid, Hazem Farag Manaa

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Background: Chronic myeloid leukemia (CML) represents 15% of adult leukemias. Imatinib Mesylate (IM) is the gold standard treatment for new cases of CML. Treatment with IM results in improvement of the majority of cases. However, about 25% of cases may develop resistance. Sensitive and specific early predictors of IM resistance in CML patients have not been established to date. Aim: To investigate the value of miR-451 in CML as an early predictor for IM resistance in Egyptian CML patients. Methods: The study employed Real time Polymerase Reaction (qPCR) technique to investigate the leucocytic expression of miR-451 in fifteen newly diagnosed CML patients (group I), fifteen IM responder CML patients (group II), fifteen IM resistant CML patients (group III) and fifteen healthy subjects of matched age and sex as a control group (group IV). The response to IM was defined as < 10% BCR-ABL transcript level after 3 months of therapy. The following parameters were assessed in subjects of all the studied groups: 1- Complete blood count (CBC). 2- Measurement of plasma level of miRNA 451 using real-time Polymerase Chain Reaction (qPCR). 3- Detection of BCR-ABL gene mutation in CML using qPCR. Results: The present study revealed that miR-451 was significantly down-regulated in leucocytes of newly diagnosed CML patients as compared to healthy subjects. IM responder CML patients showed an up-regulation of miR- 451 compared with IM resistant CML patients. Conclusion: According to the data from the present study, it can be concluded that leucocytic miR- 451 expression is a useful additional follow-up marker for the response to IM and a promising prognostic biomarker for CML.

Keywords: chronic myeloid leukemia, imatinib resistance, microRNA 451, Polymerase Chain Reaction

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Authors: Yogita Patil-Sen

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Magnetic nanoparticles such as those made of iron oxide have been widely explored as biocatalysts, contrast agents, and drug delivery systems. However, some of the challenges associated with these particles are agglomeration and biocompatibility, which lead to concern of toxicity of the particles, especially for drug delivery applications. Coating the particles with biocompatible materials such as lipids and peptides have shown to improve the mentioned issues. Thus, these core-shell type nanoparticles are emerging as the new class of nanomaterials for targeted drug delivery applications. In this study, various types of core-shell magnetic nanoparticles are prepared and characterized using techniques, such as Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Vibrating Sample Magnetometer (VSM) and Thermogravimetric Analysis (TGA). The heating ability of nanoparticles is tested under oscillating magnetic field. The efficacy of the nanoparticles as drug carrier is also investigated. The loading of an anticancer drug, Doxorubicin at 18 °C is measured up to 48 hours using UV-visible spectrophotometer. The drug release profile is obtained under thermal incubation condition at 37 °C and compared with that under the influence of oscillating field. The results suggest that the core-shell nanoparticles exhibit superparamagnetic behaviour, although, coating reduces the magnetic properties of the particles. Both the uncoated and coated particles show good heating ability, again it is observed that coating decreases the heating behaviour of the particles. However, coated particles show higher drug loading efficiency than the uncoated particles and the drug release is much more controlled under the oscillating magnetic field. Thus, the results strongly indicate the suitability of the prepared core-shell type nanoparticles as drug delivery vehicles and their potential in magnetic hyperthermia applications and for hyperthermia cancer therapy.

Keywords: core-shell, hyperthermia, magnetic nanoparticles, targeted drug delivery

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Authors: Sylwia Gieraltowska, Lukasz Wachnicki, Bartlomiej S. Witkowski, Marek Godlewski

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Oxide layers doped with rare-earth (RE) ions in optimized way can absorb short (ultraviolet light), which will be converted to visible light by so-called down-conversion. Down-conversion mechanisms are usually exploited to modify the incident solar spectrum. In down conversion, multiple low-energy photons are generated to exploit the energy of one incident high-energy photon. These RE-doped oxide materials have attracted a great deal of attention from researchers because of their potential for optical manipulation in optical devices (detectors, temperature sensors, and compact solid-state lasers, light-emitting diodes), bio-analysis, medical therapy, display technologies, and light harvesting (such as in photovoltaic cells). The zirconium dioxide (ZrO2) doped RE ions (Eu, Tb, Ce) multilayer structures were tested as active layers, which can convert short wave emission to light in the visible range (the down-conversion mechanism). For these applications original approach of deposition ZrO2 layers using the Atomic Layer Deposition (ALD) method and doping these layers with RE ions using the spin-coating technique was used. ALD films are deposited at relatively low temperature (well below 250°C). This can be an effective method to achieve the white-light emission and to improve on this way light conversion efficiency, by an extension of absorbed spectral range by a solar cell material. Photoluminescence (PL), X-ray diffraction (XRD), scanning electron microscope (SEM) and atomic force microscope (AFM) measurement are analyzed. The research was financially supported by the National Science Centre (decision No. DEC-2012/06/A/ST7/00398 and DEC- 2013/09/N/ST5/00901).

Keywords: ALD, oxide layers, photovoltaics, thin films

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Authors: Hafida Merzouk

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Urinary tract infections are among the most serious public health issues in all age groups. Thus, the empirical therapy should based on local levels of resistance, as indicated in several studies from different countries, to effectively avoid the emergence of multidrug-resistant bacterial strains and recurrent infections. Numerous effective antibiotic treatments are available, but wouldbe ineffective for treating recurrent cystitis caused by a urinary tract infection, as well as the emergence of drug resistance. That iswhy the aim of this study was to highlight the antibacterial and the antioxidant activity of 11 medicinal plants used traditionally in Algeria against E. coli, the most responsible urinary tract infections. First, the extraction of total polyphenols with aqueous acetone showed variable yields. The highest yield was obtained by Asplenium trichomanes with 27%, followed by Petroselinum crispum and Ciannamomum cassia with an equal yield of 21%. Artemisia herba-alba gave the lowest yield (9%). The extracts of different plants showed variable contents of phenolic compounds. Reducing power and DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activity revealed that most of the extracts studied had significant activity. The anti-free radical activity was very high in the extract of A splenium adiantum-nigrum compared with the other extracts studied, but Petroselinum crispum and Parietaria officinalis had the lowest reducing activity; Antibacterial activity was determined on E. coli strainsusing the diffusion, MICs (Minimum Inhibitory Concentrations) and MBCs (Minimum Bactericidal concentrations) methods. The strains tested were sensitive to most extracts studied, except Asplenium adiantum-nigrum extract, for which both strains showed resistance.

Keywords: E. coli, medicinal plants, phenolic compounds, urinary infections

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Authors: Nana Gorgiladze, Tamar Gaprindashvili, Mikheil Shavdia, Zurab Pagava

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Introduction/Purpose Chemotherapy is a common treatment for breast cancer, but it can also cause damage to the heart and blood vessels. This damage, known as cancer therapy-related cardiovascular toxicity (CTR-CVT), can increase the risk of heart failure and death in breast cancer patients. The left ventricle is often affected by CTR-CVT, but the right ventricle (RV) may also be vulnerable to CTR-CVT and may show signs of dysfunction before the left ventricle. The study aims to investigate how the RV function changes during chemotherapy for breast cancer by using conventional echocardiographic and global longitudinal strain (GLS) techniques. By measuring the GLS strain of the RV, researchers tend to detect early signs of CTR-CVT and improve the management of breast cancer patients. Methods The study was conducted on 28 women with low cardiovascular risk who received anthracycline chemotherapy for breast cancer. Conventional 2D echocardiography (LVEF, RVS’, TAPSE) and speckle-tracking echocardiography (STE) measurements of the left and right ventricles (LVGLS, RVGLS) were used to assess cardiac function before and after chemotherapy. All patients had normal LVEF at the beginning of the study. Cardiotoxicity was defined as a new LVEF reduction of 10 percentage points to an LVEF of 40-49% and/or a new decline in GLS of 15% from baseline, as proposed by the most recent cardio-oncology guideline. ResultsThe research found that the LVGLS decreased from -21.2%2.1% to -18.6%2.6% (t-test = -4.116; df = 54, p=0.001). The change in value LV-GLS was 2.6%3.0%. The mean percentage change of the LVGLS was 11,6%13,3%; p=0.001. Similarly, the right ventricular global longitudinal strain (RVGLS) decreased from -25.2%2.9% to -21.4%4.4% (t-test = -3.82; df = 54, p=0.001). The RV-GLS value of change was 3.8%3.6%. Likewise, the percentage decrease of the RVGLS was 15,0%14,3%, p=0.001.However, the measurements of the right ventricular systolic function (RVS) and tricuspid annular plane systolic excursion (TAPSE) were insignificant, and the left ventricular ejection fraction ( LVEF) remained unchanged.

Keywords: cardiotoxicity, chemotherapy, GLS, right ventricle

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Authors: Javier De La Torre Costa, Belen Rubio Ballester, Martina Maier, Paul F. M. J. Verschure

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After a stroke, a great number of patients experience persistent motor impairments such as hemiparesis or weakness in one entire side of the body. As a result, the lack of use of the paretic limb might be one of the main contributors to functional loss after clinical discharge. We aim to reverse this cycle by promoting the use of the paretic limb during activities of daily living (ADLs). To do so, we describe the key components of a system that is composed of a wearable bracelet (i.e., a smartwatch) and a mobile phone, designed to bring a set of neurorehabilitation principles that promote acquisition, retention and generalization of skills to the home of the patient. A fundamental question is whether the loss in motor function derived from learned–non–use may emerge as a consequence of decision–making processes for motor optimization. Our system is based on well-established rehabilitation strategies that aim to reverse this behaviour by increasing the reward associated with action execution as well as implicitly reducing the expected cost associated with the use of the paretic limb, following the notion of the reinforcement–induced movement therapy (RIMT). Here we validate an accelerometer–based measure of arm use, and its capacity to discriminate different activities that require increasing movement of the arm. We also show how the system can act as a personalized assistant by providing specific goals and adjusting them depending on the performance of the patients. The usability and acceptance of the device as a rehabilitation tool is tested using a battery of self–reported and objective measurements obtained from acute/subacute patients and healthy controls. We believe that an extension of these technologies will allow for the deployment of unsupervised rehabilitation paradigms during and beyond the hospitalization time.

Keywords: stroke, wearables, learned non use, hemiparesis, ADLs

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Authors: Abeer Ahmed Abdehameed

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Background: Diabetic sensorimotor polyneuropathy (DSP) is one of the most common micro vascular complications of type 2 diabetes. Loss of sensation is thought to contribute to lake of static and dynamic stability and increased risk of falling. Purpose: The purpose of this study was to compare the effects of low level laser (LLL) and monochromatic near infrared photo energy (MIRE) on pain , cutaneous sensation, static stability and index of lower limb blood flow in diabetic with peripheral neuropathy. Methods: Forty subjects with diabetic peripheral neuropathy were recruited for study. They were divided into two groups: The ( MIRE) group that included (20) patients and (LLL) group included (20) patients. All patients in the study had been subjected to various physical assessment procedures including pain, cutaneous sensation, Doppler flow meter and static stability assessments. The baseline measurements were followed by treatment sessions that conducted twice a week for 6 successive weeks. Results: The statistical analysis of the data had revealed significant improvement of the pain in both groups, with significant improvement in cutaneous sensation and static balance in (MIRE) group compared to (LLL) group; on the other hand results showed no significant differences on lower limb blood flow in both groups. Conclusion: Low level laser and monochromatic near infrared therapy can improve painful symptoms in patients with diabetic neuropathy. On the other hand (MIRE) is useful in improving cutaneous sensation and static stability in patients with diabetic neuropathy.

Keywords: diabetic neuropathy, doppler flow meter, low level laser, monochromatic near infrared photo energy

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Authors: Thinakar Mani Balusamy, Ratnakar S. Kini, Bharat Narasimhan, Venkateswaran A. R, Pugazhendi Thangavelu, Mohammed Ali, Prem Kumar K., Kani Sheikh M., Sibi Thooran Karmegam, Radhakrishnan N., Mohammed Noufal

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Introduction: Pancreatic injury remains a complicated condition requiring an individualized case by case approach to management. In this study, we aim to analyze the varied presentations and treatment outcomes of traumatic pancreatic injury in a tertiary care center. Methods: All consecutive patients hospitalized at our center with traumatic pancreatic injury between 2013 and 2017 were included. The American Association for Surgery of Trauma (AAST) classification was used to stratify patients into five grades of severity. Outcome parameters were then analyzed based on the treatment modality employed. Results: Of the 35 patients analyzed, 26 had an underlying blunt trauma with the remaining nine presenting due to penetrating injury. Overall in-hospital mortality was 28%. 19 of these patients underwent exploratory laparotomy with the remaining 16 managed nonoperatively. Nine patients had a severe injury ( > grade 3) – of which four underwent endotherapy, three had stents placed and one underwent an endoscopic pseudocyst drainage. Among those managed nonoperatively, three underwent a radiological drainage procedure. Conclusion: Mortality rates were clearly higher in patients managed operatively. This is likely a result of significantly higher degrees of major associated non-pancreatic injuries and not just a reflection of surgical morbidity. Despite this, surgical management remains the mainstay of therapy, especially in higher grades of pancreatic injury. However we would like to emphasize that endoscopic intervention definitely remains the preferred treatment modality when the clinical setting permits. This is especially applicable in cases of main pancreatic duct injury with ascites as well as pseudocysts.

Keywords: endotherapy, non-operative management, surgery, traumatic pancreatic injury

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Authors: Sudeshna Mukherjee, Leena Fageria, R. Venkataramana Dilip, Rajdeep Chowdhury, Jitendra Panwar

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Metal nanoparticles in recent years have gained importance in cancer therapy due to their enhanced permeability retention effect. Among various nanomaterials, silver nanoparticles (AgNPs) have received considerable attention due to their unique properties like conductivity, chemical stability, relative lower toxicity and outstanding therapeutic potential, such as anti-inflammatory, antimicrobial and anti-cancerous activities. In this study, we took a greener approach to synthesize silver nanoparticle from fungus and analyze its effects on both epithelial and mesenchymal derived cancer cells. Much research has been done on nanoparticle-induced apoptosis, but little is known about its role in autophagy. In our study, the silver nanoparticles were seen to induce autophagy which was analyzed by studying the expression of several autophagy markers like, LC3B-II and ATG genes. Monodansylcadaverine (MDC) assay also revealed the induction of autophagy upon treatment with AgNPs. Inhibition of autophagy by chloroquine resulted in increased cell death suggesting autophagy as a survival strategy adopted by the cells. In parallel to autophagy induction, silver nanoparticles induced ROS accumulation. Interestingly, autophagy inhibition by chloroquine increased ROS level, resulting in enhanced cell death. We further analyzed MAPK signaling upon AgNP treatment. It was observed that along with autophagy, activation of JNK signaling served as pro-survival while ERK signaling served as a pro-death signal. Our results provide valuable insights into the role of autophagy upon AgNP exposure and provide cues to probabilistic strategies to effectively sensitize cancer cells.

Keywords: autophagy, JNK signalling, reactive oxygen species, silver nanoparticles

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Authors: S. J. Higgs, E. Van Eck, K. Heynis, S. H. Broadberry

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Engagement with non-human animals is a rapidly-growing field of study within the animal science and social science sectors, with human-interactions occurring in many forms; interactions, encounters and animal-assisted therapy. To our knowledge, there has been a wide array of research published on domestic and livestock human-animal interactions, however, there appear to be fewer publications relating to zoo animals and the effect these interactions have on the animal, human and establishment. The aim of this study was to identify if there were any perceivable benefits from the human-animal interaction for the cheetah, the human and the establishment. Behaviour data were collected before, during and after the interaction on the behaviour of the cheetah and the human participants to highlight any trends with nine interactions conducted. All 35 participants were asked to fill in a questionnaire prior to the interaction and immediately after to ascertain if their perceptions changed following an interaction with the cheetah. An online questionnaire was also distributed for three months to gain an understanding of the perceptions of human-animal interactions from members of the public, gaining 229 responses. Both questionnaires contained qualitative and quantitative questions to allow for specific definitive answers to be analysed, but also expansion on the participants perceived perception of human-animal interactions. In conclusion, it was found that participants’ perceptions of human-animal interactions saw a positive change, with 64% of participants altering their opinion and viewing the interaction as beneficial for the cheetah (reduction in stress assumed behaviours) following participation in a 15-minute interaction. However, it was noted that many participants felt the interaction lacked educational values and therefore this is an area in which zoological establishments can work to further improve upon. The results highlighted many positive benefits for the human, animal and establishment, however, the study does indicate further areas for research in order to promote positive perceptions of human-animal interactions and to further increase the welfare of the animal during these interactions, with recommendations to create and regulate legislation.

Keywords: Acinonyx jubatus, encounters, human-animal interactions, perceptions, zoological establishments

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Authors: F. Bringby, A. Nordin, L. Björnådal, E. Svenungsson, C. Boström, H Alexanderson

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Patients with systemic sclerosis (SSc) have reduced hand function and self-reported limitations in daily activities. Few studies have explored limitations in shoulder-arm mobility and muscle function, or if there are differences in physical function between diffuse cutaneous (dcSSc) and limited cutaneous (lcSSc) SSc. The purpose of this study was to describe objectively assessed shoulder-arm mobility, lower extremity muscle function and muscle endurance in SSc and evaluate possible differences between lcSSc and dcSSc. 121 patients with SSc were included in this cross sectional study. Shoulder-arm mobility were examined using the Shoulder Function Assessment Scale (SFA) including 5 tasks ,lower extremity muscle function was measured by Timed stands test (TST) and muscle endurance in shoulder- and hip flexors were assessed by the Functional Index 2 (FI-2). Patients with dcSSc had median SFA hand to back score 5 (4-6) and median “hand to seat” score of 5 (4-6) compared to patients with lcSSc with corresponding median values of 6 (4-6) and 6 (5-6) respectively (p<0.01-p<0.05). 50% of both patientsgroups had lower muscle function assessed by the TST compared to age- and gender matched reference values but there were no differences in TST between the two patient groups. There was no difference in FI-2 scores between dcSSc and lcSSc. The whole group had 40 (28-83) % and 38 (32-72) % of maximal FI-2 shoulder flexion score on the right and left sides, and 40 (23-63) % and 37 (23-62) % of maximal FI-2 hip flexion score on the right and left sides. Reference values for the FI-2 indicate that healthy individuals perform in mean 100 % of maximal score. Patients with dcSSc were more limited than patients with lcSSc. Patients with SSc have reduced muscle function compared to reference values. These results highlights the importance of assessing shoulder-arm mobility and muscle function as well as a need for further research to identify exercise interventions to target these limitations.

Keywords: diffuse, limited, mobility, muscle function, physical therapy, systemic sclerosis

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Authors: Anamika A. Sharma, Arezou Ahmadi R. A., Narendra B. Parihar, Manjusha Sajith

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Introduction: Hemodialysis is the most effective therapeutic technique for patient with ESRD second to renal transplantation. However it is a lifelong therapy which requires frequent hospital, or dialysis centers visits mainly twice and thrice weekly, thus considerably changes the normal way of patient’s living. So this study aimed to Assess Health-Related Quality of life in End-Stage Renal Disease (ESRD) Undergoing Twice and Thrice weekly Hemodialysis. Method: A prospective observational, cross-sectional study was carried out from September 2016 to April 2017 in end-stage renal disease patients undergoing hemodialysis. Socio-demographic and clinical details of patients were obtained from the medical records. WHOQOL-BREF questionnaire was used to Access Health-Related Quality Of Life. Quality of Life scores of Twice weekly and Thrice weekly hemodialysis was analyzed by Kruskal Wallis Test. Results: Majority of respondents were male (72.55%), married (89.31%), employed (58.02%), belong to middle class (71.00%) and resides in rural area (58.78%). The mean ages in the patient undergoing twice weekly and thrice weekly hemodialysis were 51.89 ± 15.64 years and 51.33 ± 15.70 years respectively. Average Quality of Life scores observed in twice weekly and thrice weekly hemodialysis was 52.07 ± 13.30 (p=0.0037) and 52.87 ± 13.47 (p=0.0004) respectively. The hemoglobin of thrice weekly dialysis patients (10.28 gm/dL) was high as compared to twice weekly dialysis (9.23 gm/dL). Patients undergoing thrice weekly dialysis had improved serum urea, serum creatinine values (95.85 mg/dL, 8.32 mg/dL) as compared to twice weekly hemodialysis ( 104.94 mg/dL, 8.68 mg/dL). Conclusion: Our study concluded that there was no significant difference between overall Health-Related Quality Of Life in twice weekly and thrice weekly hemodialysis. Frequent hemodialysis was associated with improved control of hypertension, serum urea, serum creatinine levels.

Keywords: end stage renal disease, health related quality of life, twice weekly hemodialysis, thrice weekly hemodialysis

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Authors: Bulcha Belay Etana, Benny Malengier, Janarthanan Krishnamoorthy, Timothy Kwa, Lieva VanLangenhove

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Electromyography measures the electrical activity of muscles using surface electrodes or needle electrodes to monitor various disease conditions. Recent developments in the signal acquisition of electromyograms using textile electrodes facilitate wearable devices, enabling patients to monitor and control their health status outside of healthcare facilities. Here, we have developed and tested wearable textile electrodes to acquire electromyography signals from patients suffering from Parkinson’s disease and incorporated a feedback-control system to relieve muscle cramping through thermal stimulus. In brief, the textile electrodes made of stainless steel was knitted into a textile fabric as a sleeve, and their electrical characteristic, such as signal-to-noise ratio, was compared with traditional electrodes. To relieve muscle cramping, a heating element made of stainless-steel conductive yarn sewn onto cotton fabric, coupled with a vibration system, was developed. The system integrated a microcontroller and a Myoware muscle sensor to activate the heating element as well as the vibration motor when cramping occurs, and at the same time, the element gets deactivated when the muscle cramping subsides. An optimum therapeutic temperature of 35.5 °C is regulated by continuous temperature monitoring to deactivate the heating system when this threshold value is reached. The textile electrode exhibited a signal-to-noise ratio of 6.38dB, comparable to that of the traditional electrode’s value of 7.05 dB. For a given 9 V power supply, the rise time was about 6 minutes for the developed heating element to reach an optimum temperature.

Keywords: smart textile system, wearable electronic textile, electromyography, heating textile, vibration therapy, Parkinson’s disease

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Authors: Mohamed Aly, Aliaa Rehan Youssef, Emad Sawerees, Mounir Guirgis

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Relevance: Osteoarthritis (OA) is the most common degenerative disease seen in all populations. It causes disability and substantial socioeconomic burden. Evidence supports that exercise are the most effective conservative treatment for patients with OA. Therapists experience and clinical judgment play major role in exercise prescription and scientific evidence for this regard is lacking. The development of clinical prediction rules to identify patients who are most likely benefit from exercise may help solving this dilemma. Purpose: This study investigated whether body mass index and functional ability at baseline can predict patients’ response to a selected exercise program. Approach: Fifty-six patients, aged 35 to 65 years, completed an exercise program consisting of open kinetic chain strengthening and passive stretching exercises. The program was given for 3 sessions per week, 45 minutes per session, for 6 weeks Evaluation: At baseline and post treatment, pain severity was assessed using the numerical pain rating scale, whereas functional ability was being assessed by step test (ST), time up and go test (TUG) and 50 feet time walk test (50 FTW). After completing the program, global rate of change (GROC) score of greater than 4 was used to categorize patients as successful and non-successful. Thirty-eight patients (68%) had successful response to the intervention. Logistic regression showed that BMI and 50 FTW test were the only significant predictors. Based on the results, patients with BMI less than 34.71 kg/m2 and 50 FTW test less than 25.64 sec are 68% to 89% more likely to benefit from the exercise program. Conclusions: Clinicians should consider the described strengthening and flexibility exercise program for patents with BMI less than 34.7 Kg/m2 and 50 FTW faster than 25.6 seconds. The validity of these predictors should be investigated for other exercise.

Keywords: clinical prediction rule, knee osteoarthritis, physical therapy exercises, validity

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Authors: Marji Umil, Miane Karyle Urolaza, Ian Winston Dale Uy, John Charle Magne Valdez, Karen Elizabeth Valdez, Ervin Charles Valencia, Cheryleen Tan-Chua

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Objective: Distraction techniques can be successful in reducing the anxiety of children during medical procedures. Dental procedures, in particular, are associated with dental anxiety which has been identified as a significant and common problem in children, however, only limited studies were conducted to address such problem. Thus, this study determined the effectiveness of computer video games on the levels of anxiety of children between 5-12 years old scheduled for tooth extraction. Methods: A pre-test post-test quasi-experimental study was conducted involving 30 randomly-assigned subjects, 15 in the experimental and 15 in the control. Subjects in the experimental group played computer video games for a maximum of 15 minutes, however, no intervention was done on the control. The modified Yale Pre-operative Anxiety Scale (m-YPAS) with a Cronbach’s alpha of 0.9 was used to assess anxiety at two different points: upon arrival in the clinic (pre-test anxiety) and 15 minutes after the first measurement (post-test anxiety). Paired t-test and ANCOVA were used to analyze the gathered data. Results: Results showed that there is a significant difference between the pre-test and post-test anxiety scores of the control group (p=0.0002) which indicates an increased anxiety. A significant difference was also noted between the pre-test and post-test anxiety scores of the experimental group (p=0.0002) which indicates decreased anxiety. Comparatively, the experimental group showed lower anxiety score (p=<0.0001) than the control. Conclusion: The use of computer video games is effective in reducing the pre-operative anxiety among children and can be an alternative non-pharmacological management in giving pre-operative care.

Keywords: play therapy, preoperative anxiety, tooth extraction, video games

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Authors: Pratibha Goyal, Nupur Mathur, Anuradha Singh

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Antibiotic resistance is the worldwide threat to human health in this century. Excessive use of antibiotic after their discovery in 1940 makes certain bacteria to become resistant against antibiotics. Most common antibiotic-resistant bacteria include Staphylococcus aureus, Salmonella typhi, E.coli, Klebsiella pneumonia, and Streptococcus pneumonia. Among all Staphylococcus resistant strain called Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for several lives threatening infection in human commonly found in the hospital environment. Our study aimed to isolate bacteriophage against MRSA from the hospital sewage treatment plant and to analyze its efficiency In Vivo in Swiss albino mice model. Sewage sample for the isolation of bacteriophages was collected from SDMH hospital sewage treatment plant in Jaipur. Bacteriophages isolated by the use of enrichment technique and after characterization, isolated phages used to determine phage treatment efficiency in mice. Mice model used to check the safety and suitability of phage application in human need which in turn directly support the use of natural bacteriophage rather than synthetic chemical to kill pathogens. Results show the plaque formation in-vitro and recovery of MRSA infected mice during the experiment. Favorable lytic efficiency determination of MRSA and Salmonella presents a natural way to treat lethal infections caused by Multidrug-resistant bacteria by using their natural host-pathogen relationship.

Keywords: antibiotic resistance, bacteriophages, methicillin resistance Staphylococcus aureus, pathogens, phage therapy, Salmonella typhi

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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: 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: 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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