Search results for: superficial discovery

Authors: Marina Arino Martin, John McEvoy, Eakalak Khan

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Endoxifen is an active metabolite responsible for the effectiveness of tamoxifen, a chemotherapeutic drug widely used for endocrine responsive breast cancer and chemo-preventive long-term treatment. Tamoxifen and endoxifen are not completely metabolized in human body and are actively excreted. As a result, they are released to the water environment via wastewater treatment plants (WWTPs). The presence of tamoxifen in the environment produces negative effects on aquatic lives due to its antiestrogenic activity. Because endoxifen is 30-100 times more potent than tamoxifen itself and also presents antiestrogenic activity, its presence in the water environment could result in even more toxic effects on aquatic lives compared to tamoxifen. Data on actual concentrations of endoxifen in the environment is limited due to recent discovery of endoxifen pharmaceutical activity. However, endoxifen has been detected in hospital and municipal wastewater effluents. The detection of endoxifen in wastewater effluents questions the treatment efficiency of WWTPs. Studies reporting information about endoxifen removal in WWTPs are also scarce. There was a study that used chlorination to eliminate endoxifen in wastewater. However, an inefficient degradation of endoxifen by chlorination and the production of hazardous disinfection by-products were observed. Therefore, there is a need to remove endoxifen from wastewater prior to chlorination in order to reduce the potential release of endoxifen into the environment and its possible effects. The aim of this research is to isolate and identify bacteria strain(s) capable of degrading endoxifen into less hazardous compound(s). For this purpose, bacteria strains from WWTPs were exposed to endoxifen as a sole carbon and nitrogen source for 40 days. Bacteria presenting positive growth were isolated and tested for endoxifen biodegradation. Endoxifen concentration and by-product formation were monitored. The Monod kinetic model was used to determine endoxifen biodegradation rate. Preliminary results of the study suggest that isolated bacteria from WWTPs are able to growth in presence of endoxifen as a sole carbon and nitrogen source. Ongoing work includes identification of these bacteria strains and by-product(s) of endoxifen biodegradation.

Keywords: biodegradation, bacterial degraders, endoxifen, wastewater

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Authors: E. M. Rifqi Wilda Pradana, Bagus Bayu Prabowo, Meida Riski Pujiyati, Efraim Maykhel Hagana Ginting, Virgiawan Arya Hangga Reksa

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The VLF (Very Low Frequency) method is an electromagnetic method that uses low frequencies between 10-30 KHz which results in a fairly deep penetration. In this study, the VLF method was used for zonation of disaster-prone areas by identifying geological structures in the form of faults. Data acquisition was carried out in Trimulyo Region, Jetis District, Bantul Regency, Special Region of Yogyakarta, Indonesia with 8 measurement paths. This study uses wave transmitters from Japan and Australia to obtain Tilt and Elipt values that can be used to create RAE (Rapat Arus Ekuivalen or Current Density) sections that can be used to identify areas that are easily crossed by electric current. This section will indicate the existence of a geological structure in the form of faults in the study area which is characterized by a high RAE value. In data processing of VLF method, it is obtained Tilt vs Elliptical graph and Moving Average (MA) Tilt vs Moving Average (MA) Elipt graph of each path that shows a fluctuating pattern and does not show any intersection at all. Data processing uses Matlab software and obtained areas with low RAE values that are 0%-6% which shows medium with low conductivity and high resistivity and can be interpreted as sandstone, claystone, and tuff lithology which is part of the Semilir Formation. Whereas a high RAE value of 10% -16% which shows a medium with high conductivity and low resistivity can be interpreted as a fault zone filled with fluid. The existence of the fault zone is strengthened by the discovery of a normal fault on the surface with strike N550W and dip 630E at coordinates X= 433256 and Y= 9127722 so that the activities of residents in the zone such as housing, mining activities and other activities can be avoided to reduce the risk of natural disasters.

Keywords: current density, faults, very low frequency, zonation

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Authors: Palaniyandi Karuppaiya, Hsin Sheng Tsay, Fang Chen

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Medicinal herbs do represent a huge and noteworthy reservoir for novel anticancer drugs discovery. Dysosma pleiantha (Hance) Woodson (Berberidaceae), one of the oldest traditional Chinese medicinal herb, highly prized by the mountain tribes of Taiwan and China for its medicinal properties contained pharmaceutically important antitumor compounds podophyllotoxin, quercetin and kaempferol. Among lignans, podophyllotoxin is an active antitumor compound and has now been modified to produce clinically useful drugs etoposide and teniposide. In recent years, natural populations of D. peliantha have declined considerably due to anthropogenic activities such as habitat destruction and commercial exploitation for medicinal applications. As to its overall conservation status, D. pleiantha has been ranked as threatened on the China Species Red List. In the present study, an efficient in vitro callus culture system of D. pleiantha was established on Gamborg’s medium with various combinations and concentrations of different auxins and cytokinins under dark condition. Best callus induction was recorded in 2 mg/L 2, 4 - Dichlorophenoxyacetic acid (2,4-D) along with 0.2 mg/L kinetin and the maximum callus proliferation was achieved at 1 mg/L 2,4-D. Among the explants tested, maximum callus induction (86 %) was achieved from tender leaves. Hence, in subsequent experiments, leaf callus was further investigated for suitable callus biomass and production level of anticancer compounds under the influence of different additives. A maximum fresh callus biomass (8.765 g) was recorded in callus proliferation medium contained 500 mg/L casein hydrolysate. High performance liquid chromatography results revealed that the addition of different concentrations of peptone (1, 2 and 4 g/L) in callus proliferation medium enhanced podophyllotoxin (16 fold), quercetin (12 fold) and kaempferol (5 fold) accumulation than control. Thus, the established in vitro callus culture under the influence of different additives may offer an alternative source of enhanced production of podophyllotoxin, kaempferol and quecertin without harming natural plant population.

Keywords: dysosma pleiantha, kaempferol, podophyllotoxin, quercetin

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Authors: Guilherme Oliveira

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The assimilation of images and their potential symbolism into lived experiences is inherent. It is through this exercise of recognition via imagistic records that the questioning of the origins of a constant narrative stimulated by the media arises. The construction of the "Man" archetype and the reflections of active masculine imagery in the 21st century, when conveyed through media channels, could potentially have detrimental effects. Addressing this systematic behavioral chronology of virile cisgender, permeated imagistically through these means, involves exploring potential resolutions. Thus, an investigation process is initiated into the potential representation of the 'hero' in this media emulation through idols contextualized in the political sphere, with the purpose of elucidating the processes of simulation and emulation of narratives based on mythical, historical, and sacred accounts. In this process of sharing, the narratives contained in the imagistic structuring offered by information dissemination channels seek validation through a process of public acceptance. To achieve this consensus, a visual set adorned with mythological and sacred symbolisms adapted to the intended environment is promoted, thus utilizing sociocultural characteristics in favor of political marketing. Visual recognition, therefore, becomes a direct reflection of a cultural heritage acquired through lived human experience, stimulated by continuous representations throughout history. Echoes of imagery and narratives undergo a constant process of resignification of their concepts, sharpened by their premises, and adapted to the environment in which they seek to establish themselves. Political figures analyzed in this article employ the practice of taking possession of symbolisms, mythological stories, and heroisms and adapt their visual construction through a continuous praxis of emulation. Thus, they utilize iconic mythological narratives to gain credibility through belief. Utilizing iconic mythological narratives for credibility through belief, the idol becomes the very act of release of trauma, offering believers liberation from preconceived concepts and allowing for the attribution of new meanings. To dissolve this issue and highlight the subjectivities within the intention of the image, a linguistic, semiotic, and anthropological methodology is created. Linguistics uses expressions like 'Blaming the Image' to create a mechanism of expressive action in questioning why to blame a construction or visual composition and thus seek answers in the first act. Semiotics and anthropology develop an imagistic atlas of graphic analysis, seeking to make connections, comparisons, and relations between modern and sacred/mystical narratives, emphasizing the different subjective layers of embedded symbolism. Thus, it constitutes a performative act of disarming the image. It creates a disenchantment of the superficial gaze under the constant reproduction of visual content stimulated by virtual networks, enabling a discussion about the acceptance of caricatures characterized by past fables.

Keywords: image, heroic narrative, media heroism, virile politics, political, myth, sacred performance, visual mythmaking, characterization dynamics

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Authors: Djebbar Atmani, Aghiles Karim Aissat, Nadjet Debbache-Benaida, Nassima Chaher-Bazizi, Dina Atmani-Kilani, Meriem Rahmani-Berboucha, Naima Saidene, Malika Benloukil, Lila Azib

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Medicinal plants are believed to be an important source for the discovery of potential antioxidant, anti-inflammatory and anti-diabetic substances. The present study was designed to investigate the neuroprotective, anti-inflammatory, anti-diabetic and anti-hyperuricemic potential of Pistacia lentiscus, as well as the identification of active compounds. The antioxidant potential of plant extracts against known radicals was measured using various standard in vitro methods. Anti-inflammatory activity was determined using the paw edema model in mice and by measuring the secretion of the pro-inflammatory cytokine, whereas the anti-diabetic effect was assessed in vivo on streptozotocin-induced diabetic rats and in vitro by inhibition of alpha-amylase. The anti-hyperuricemic activity was evaluated using the xanthine oxidase assay, whereas neuroprotective activity was investigated using an Aluminum-induced toxicity test. Pistacia lentiscus extracts and fractions exhibited high scavenging capacity against DPPH, NO. and ABTS+ radicals in a dose-dependent manner and restored blood glucose levels, in vivo, to normal values, in agreement with the in vitro anti-diabetic effect. Oral administration of plant extracts significantly decreased carrageenan-induced mice paw oedema, similar to the standard drug, diclofenac, was effective in reducing IL-1β levels in cell culture and induced a significant increase in urinary volume in mice, associated to a promising anti-hyperuricemic activity. Plant extracts showed good neuroprotection and restoration of cognitive functions in mice. HPLC-MS and NMR analyses allowed the identification of known and new phenolic compounds that could be responsible for the observed activities. Therefore, Pistacia lentiscus could be beneficial in the treatment of inflammatory conditions and diabetes complications and the enhancement of cognitive functions.

Keywords: Pistacia lentiscus, anti-inflammatory, antidiabetic, flavanols, neuroprotective

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Authors: Eric Lacoste

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Laboratory animals are currently widely used as a model of human pathologies in dermatology such as atopic dermatitis (AD). These models provide a better understanding of the pathophysiology of this complex and multifactorial disease, the discovery of potential new therapeutic targets and the testing of the efficacy of new therapeutics. However, confirmation of the correct development of AD is mainly based on histology from skin biopsies requiring invasive surgery or euthanasia of the animals, plus slicing and staining protocols. However, there are currently accessible imaging technologies such as Optical Coherence Tomography (OCT), which allows non-invasive visualization of the main histological structures of the skin (like stratum corneum, epidermis, and dermis) and assessment of the dynamics of the pathology or efficacy of new treatments. Briefly, female immunocompetent hairless mice (SKH1 strain) were sensitized and challenged topically on back and ears for about 4 weeks. Back skin and ears thickness were measured using calliper at 3 occasions per week in complement to a macroscopic evaluation of atopic dermatitis lesions on back: erythema, scaling and excoriations scoring. In addition, OCT was performed on the back and ears of animals. OCT allows a virtual in-depth section (tomography) of the imaged organ to be made using a laser, a camera and image processing software allowing fast, non-contact and non-denaturing acquisitions of the explored tissues. To perform the imaging sessions, the animals were anesthetized with isoflurane, placed on a support under the OCT for a total examination time of 5 to 10 minutes. The results show a good correlation of the OCT technique with classical HES histology for skin lesions structures such as hyperkeratosis, epidermal hyperplasia, and dermis thickness. This OCT imaging technique can, therefore, be used in live animals at different times for longitudinal evaluation by repeated measurements of lesions in the same animals, in addition to the classical histological evaluation. Furthermore, this original imaging technique speeds up research protocols, reduces the number of animals and refines the use of the laboratory animal.

Keywords: atopic dermatitis, mouse model, oxzolone model, histology, imaging

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Authors: Endris Yibru Hanurry, Wei-Hsin Hsu, Hsieh-Chih Tsai

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In recent years, the discovery of small interfering RNAs (siRNAs) has got great attention for the treatment of cancer and other diseases. However, the therapeutic efficacy of siRNAs has been faced with many drawbacks because of short half-life in blood circulation, poor membrane penetration, weak endosomal escape and inadequate release into the cytosol. To overcome these drawbacks, we designed a non-viral vector by conjugating polyamidoamine generation 4.5 dendrimer (PDG4.5) with diethylenetriamine (DETA)- and tetraethylenepentamine (TEPA) followed by binding with siRNA to form polyplexes through electrostatic interaction. The result of 1H nuclear magnetic resonance (NMR), 13C NMR, correlation spectroscopy, heteronuclear single–quantum correlation spectroscopy, and Fourier transform infrared spectroscopy confirmed the successful conjugation of DETA and TEPA with PDG4.5. Then, the size, surface charge, morphology, binding ability, stability, release assay, toxicity and cellular internalization were analyzed to explore the physicochemical and biological properties of PDG4.5-DETA and PDG4.5-TEPA polyplexes at specific N/P ratios. The polyplexes (N/P = 8) exhibited spherical nanosized (125 and 85 nm) particles with optimum surface charge (13 and 26 mV), showed strong siRNA binding ability, protected the siRNA against enzyme digestion and accepted biocompatibility to the HeLa cells. Qualitatively, the fluorescence microscopy image revealed the delocalization (Manders’ coefficient 0.63 and 0.53 for PDG4.5-DETA and PDG4.5-TEPA, respectively) of polyplexes and the translocation of the siRNA throughout the cytosol to show a decent cellular internalization and intracellular biodistribution of polyplexes in HeLa cells. Quantitatively, the flow cytometry result indicated that a significant (P < 0.05) amount of siRNA was internalized by cells treated with PDG4.5-DETA (68.5%) and PDG4.5-TEPA (73%) polyplexes. Generally, PDG4.5-DETA and PDG4.5-TEPA were ideal nanocarriers of siRNA in vitro and might be used as promising candidates for in vivo study and future pharmaceutical applications.

Keywords: non-viral carrier, oligoalkylamine, poly(amidoamine) dendrimer, polyplexes, siRNA

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Authors: Parimalah Velo, Ahmad Zakaria

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Introduction: Monte Carlo simulations of preclinical imaging systems allow opportunity to enable new research that could range from designing hardware up to discovery of new imaging application. The simulation system which could accurately model an imaging modality provides a platform for imaging developments that might be inconvenient in physical experiment systems due to the expense, unnecessary radiation exposures and technological difficulties. The aim of present study is to validate the Monte Carlo simulation of thyroid phantom imaging using Geant4-GATE for Siemen’s e-cam single head gamma camera. Upon the validation of the gamma camera simulation model by comparing physical characteristic such as energy resolution, spatial resolution, sensitivity, and dead time, the GATE simulation of thyroid phantom imaging is carried out. Methods: A thyroid phantom is defined geometrically which comprises of 2 lobes with 80mm in diameter, 1 hot spot, and 3 cold spots. This geometry accurately resembling the actual dimensions of thyroid phantom. A planar image of 500k counts with 128x128 matrix size was acquired using simulation model and in actual experimental setup. Upon image acquisition, quantitative image analysis was performed by investigating the total number of counts in image, the contrast of the image, radioactivity distributions on image and the dimension of hot spot. Algorithm for each quantification is described in detail. The difference in estimated and actual values for both simulation and experimental setup is analyzed for radioactivity distribution and dimension of hot spot. Results: The results show that the difference between contrast level of simulation image and experimental image is within 2%. The difference in the total count between simulation and actual study is 0.4%. The results of activity estimation show that the relative difference between estimated and actual activity for experimental and simulation is 4.62% and 3.03% respectively. The deviation in estimated diameter of hot spot for both simulation and experimental study are similar which is 0.5 pixel. In conclusion, the comparisons show good agreement between the simulation and experimental data.

Keywords: gamma camera, Geant4 application of tomographic emission (GATE), Monte Carlo, thyroid imaging

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Authors: Qudsiya Baig

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Empathy yields an unparalleled therapeutic value within patient physician interactions. Medical research is inundated with evidence to support that a physician’s ability to empathise with patients leads to a greater willingness to report symptoms, an improvement in diagnostic accuracy and safety, and a better adherence and satisfaction with treatment plans. Furthermore, the Institute of Medicine states that empathy leads to a more patient-centred care, which is one of the six main goals of a 21st century health system. However, there is a paradox between the theoretical significance of empathy and its presence, or lack thereof, in clinical practice. Recent studies have reported that empathy declines amongst students and physicians over time. The three most impactful contributors to this decline are: (1) disagreements over the definitions of empathy making it difficult to implement it into practice (2) poor consideration or regulation of empathy leading to burnout and thus, abandonment altogether, and (3) the lack of diversity in the curriculum and the influence of medical culture, which prioritises science over patient experience, limiting some physicians from using ‘too much’ empathy in the fear of losing clinical objectivity. These issues were investigated by conducting a fully inductive thematic narrative analysis of patient narratives in the UK to evaluate the behaviours and attitudes that patients associate with empathy. The principal enquiries underpinning this study included uncovering the factors that affected experience of empathy within provider-patient interactions and to analyse their effects on patient care. This research contributes uniquely to this discourse by examining the phenomenon of empathy directly from patients’ experiences, which were systematically extracted from a repository of online patient narratives of care titled ‘CareOpinion UK’. Narrative analysis was specifically chosen as the methodology to examine narratives from a phenomenological lens to focus on the particularity and context of each story. By enquiring beyond the superficial who-whatwhere, the study of narratives prescribed meaning to illness by highlighting the everyday reality of patients who face the exigent life circumstances created by suffering, disability, and the threat of life. The following six themes were found to be the most impactful in influencing the experience of empathy: dismissive behaviours, judgmental attitudes, undermining patients’ pain or concerns, holistic care and failures and successes of communication or language. For each theme there were overarching themes relating to either a failure to understand the patient’s perspective or a success in taking a person-centred approach. An in-depth analysis revealed that a lack of empathy was greatly associated with an emotive-cognitive imbalance, which disengaged physicians with their patients’ emotions. This study hereby concludes that competent providers require a combination of knowledge, skills, and more importantly empathic attitudes to help create a context for effective care. The crucial elements of that context involve (a) identifying empathy clues within interactions to engage with patients’ situations, (b) attributing a perspective to the patient through perspective-taking and (c) adapting behaviour and communication according to patient’s individual needs. Empathy underpins that context, as does an appreciation of narrative, and the two are interrelated.

Keywords: empathy, narratives, person-centred, perspective, perspective-taking

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Authors: Arpit Kumar Shrivastava, Subrat Kumar, Rajani Kanta Mohapatra, Priyadarshi Soumyaranjan Sahu

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Computational approaches to predict structure, function and other biological characteristics of proteins are becoming more common in comparison to the traditional methods in drug discovery. Cryptosporidiosis is a major zoonotic diarrheal disease particularly in children, which is caused primarily by Cryptosporidium hominis and Cryptosporidium parvum. Currently, there are no vaccines for cryptosporidiosis and recommended drugs are not effective. With the availability of complete genome sequence of C. hominis, new targets have been recognized for the development of effective and better drugs and/or vaccines. We identified a unique hypothetical epitopic protein in C. hominis genome through BLASTP analysis. A 3D model of the hypothetical protein was generated using I-Tasser server through threading methodology. The quality of the model was validated through Ramachandran plot by PROCHECK server. The functional annotation of the hypothetical protein through DALI server revealed structural similarity with human Transportin 3. Phylogenetic analysis for this hypothetical protein also showed C. hominis hypothetical protein (CUV04613) was the closely related to human transportin 3 protein. The 3D protein model is further subjected to virtual screening study with inhibitors from the Zinc Database by using Dock Blaster software. Docking study reported N-(3-chlorobenzyl) ethane-1,2-diamine as the best inhibitor in terms of docking score. Docking analysis elucidated that Leu 525, Ile 526, Glu 528, Glu 529 are critical residues for ligand–receptor interactions. The molecular dynamic simulation was done to access the reliability of the binding pose of inhibitor and protein complex using GROMACS software at 10ns time point. Trajectories were analyzed at each 2.5 ns time interval, among which, H-bond with LEU-525 and GLY- 530 are significantly present in MD trajectories. Furthermore, antigenic determinants of the protein were determined with the help of DNA Star software. Our study findings showed a great potential in order to provide insights in the development of new drug(s) or vaccine(s) for control as well as prevention of cryptosporidiosis among humans and animals.

Keywords: cryptosporidium hominis, hypothetical protein, molecular docking, molecular dynamics simulation

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Authors: Karol Rodriguez-Peña, Martha L. Macias-Rubalcava, Leticia Rocha-Zavaleta, Sergio Sanchez

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A bioassay-guided study for anti-cancer compounds from endophytes of the Mexican medicinal plant Amphipteryygium adstringens resulted in the isolation of a streptomycete capable of producing a group of compounds with high cytotoxic activity. Microorganisms from surface sterilized samples of various sections of the plant were isolated and all the actinomycetes found were evaluated for their potential to produce compounds with cytotoxic activity against cancer cell lines MCF7 (breast cancer) and HeLa (cervical cancer) as well as the non-tumoural cell line HaCaT (keratinocyte). The most active microorganism was picked for further evaluation. The identification of the microorganism was carried out by 16S rDNA gene sequencing, finding the closest proximity to Streptomyces scabrisporus, but with the additional characteristic that the strain isolated in this study was capable of producing colorful compounds never described for this species. Crude extracts of dichloromethane and ethyl acetate showed IC50 values of 0.29 and 0.96 μg/mL for MCF7, 0.51 and 1.98 μg/mL for HeLa and 0.96 and 2.7 μg/mL for HaCaT. Scaling the fermentation to 10 L in a bioreactor generated 1 g of total crude extract, which was fractionated by silica gel open column to yield 14 fractions. Nine of the fractions showed cytotoxic activity. Fraction 4 was chosen for subsequent purification because of its high activity against cancerous cell lines, lower activity against keratinocytes. HPLC-UV-MS/ESI was used for the evaluation of this fraction, finding at least 10 different compounds with high values of m/z (≈588). Purification of the compounds was carried out by preparative thin-layer chromatography. The prevalent compound was Steffimycin B, a molecule known for its antibiotic and cytotoxic activities and also for its low solubility in aqueous solutions. Along with steffimycin B, another five compounds belonging to the steffimycin family were isolated and at this moment their structures are being elucidated, some of which display better solubility in water: an attractive property for the pharmaceutical industry. As a conclusion to this study, the isolation of endophytes resulted in the discovery of a strain capable of producing compounds with high cytotoxic activity that need to be studied for their possible utilization.

Keywords: amphipterygium adstringens, cytotoxicity, streptomyces scabrisporus, steffimycin

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Authors: Constâncio Augusto Machanguana

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The world over, resettling communities, for whatever purpose (mining, dams, forestry and wildlife management, roads, or facilitating services delivery), often leads to tensions between those resettled, the investors, and the local and national governments involved in the process. Causes include unclear government legislation and regulations, confusing Corporate Social Responsibility policies and guidelines, and other social-economic policies leading to unrealistic expectations among those being resettled, causing frustrations within the community, shifting them to any imminent conflict against the investors (company). The exploitation of heavy mineral sands along Mozambique’s long coastline and hinterland has not been providing a benefit for the affected communities. A case in point is the exploration, since 2018, of heavy sands in Chibuto District in the Southern Province of Gaza. A likely contributing factor is the standard type of socio-economic surveys and community involvement processes that could smooth the relationship among the parties. This research aims to investigate alternative processes to plan, initiate and guide resettlement processes in such a way that tensions and conflicts are avoided. Based on the process already finished, compared to similar cases along with the country, mixed methods to collect primary data were adopted: three focus groups of 125 people, representing 324 resettled householders; five semi-structured interviews with relevant stakeholders such as the local government, NGO’s and local leaders to understand their role in all stages of the process. The preliminary results show that the community has limited or no understanding of the potential impacts of these large-scale explorations, and the apparent harmony between the parties (community and company) may hide the dissatisfaction of those resettled. So, rather than focusing on negative mining impacts, the research contributes to science by identifying the best resettlement approach that can be replicated in other contexts along with the country in the actual context of the new discovery of mineral resources.

Keywords: conflict mitigation, resettlement, mining, Mozambique

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Authors: Xiaoshuang Jia, Huiling Feng, Li Niu, Wei Hai

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Led by Humanistic Beijing Studies Center in Renmin University of China, My Peking Memory Project(MPMP) is a long-time digital memory project under guarantee of public participation to enable the cultural and intellectual memory of Beijing to be collected, organized, preserved and promoted for discovery and research. Taking digital memory as a new way, MPMP is an important part of Peking Memory Project(PMP) which is aimed at using digital technologies to protect and (re)present the cultural heritage in Beijing. The key outcome of MPMP is the co-building of a total digital collection of knowledge assets about Beijing. Institutional memories are central to Beijing’s collection and consist of the official published documentary content of Beijing. These have already fall under the archival collection purview. The advances in information and communication technology and the knowledge form social memory theory have allowed us to collect more comprehensively beyond institutional collections. It is now possible to engage citizens on a large scale to collect private memories through crowdsourcing in digital formats. Private memories go beyond official published content to include personal narratives, some of which are just in people’s minds until they are captured by MPMP. One aim of MPMP is to engage individuals, communities, groups or institutions who have formed memories and content about Beijing, and would like to contribute them. The project hopes to build a culture of remembering and it believes ‘Every Memory Matters’. Digital memory contribution was achieved through the development of the MPMP. In reducing barriers to digital contribution and promoting high public Participation, MPMP has taken explored the harvesting of transcribe service for digital ingestion, mobile platform and some off-line activities like holding social forum. MPMP has also cooperated with the ‘Implementation Plan of Support Plan for Growth of Talents in Renmin University of China’ to get manpower and intellectual support. After six months of operation, now MPMP have more than 2000 memories added and 7 Special Memory Collections now online. The work of MPMP has ultimately helped to highlight the important role in safeguarding the documentary heritage and intellectual memory of Beijing.

Keywords: digital memory, public participation, MPMP, cultural heritage, collection

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Authors: M. P. S. Tomar, Neelam Bansal

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Histomorphological, histochemical and scanning electron microscopic observations were recorded in developing cornea of buffalo fetuses. The samples from fetal cornea were collected in appropriate fixative from slaughter house and Veterinary Clinics, GADVASU, Ludhiana. The microscopic slides were stained for detailed histomorphological and histochemical studies. The scanning electron microscopic studies were performed at Electron microscopy & Nanobiology Lab, PAU Ludhiana. In present study, it was observed that, in 36 days (d) fetus, the corneal epithelium was well marked single layered structure which was placed on stroma mesenchyme. Cornea appeared as the continuation of developing sclera. The thickness of cornea and its epithelium increased as well as the epithelium started becoming double layered in 47d fetus at corneo-scleral junction. The corneal thickness in this stage suddenly increased thus easily distinguished from developing sclera. The separation of corneal endothelium from stroma was evident as a single layered epithelium. The stroma possessed numerous fibroblasts in 49d stage eye. Descemet’s membrane was appeared at 52d stage. The limbus area was separated by a depression from the developing cornea in 61d stage. In 65d stage, the Bowman’s layer was more developed. Fibroblasts were arranged parallel to each other as well as parallel to the surface of developing cornea in superficial layers. These fibroblasts and fibers were arranged in wavy pattern in the center of stroma. Corneal epithelium started to be stratified as a double layered epithelium was present in this age of fetal eye. In group II (>120 Days), the corneal epithelium was stratified towards a well marked irido-corneal angle. The stromal fibroblasts followed a complete parallel arrangement in its entire thickness. In full term fetuses, a well developed cornea was observed. It was a fibrous layer which had five distinct layers. From outside to inwards were described as the outer most layer was the 7-8 layered corneal epithelial, subepithelial basement membrane (Bowman’s membrane), substantia propria or stroma, posterior limiting membrane (Descemet’s membrane) and the posterior epithelium (corneal endothelium). The corneal thickness and connective tissue elements were continued to be increased. It was 121.39 + 3.73µ at 36d stage which increased to 518.47 + 4.98 µ in group III fetuses. In fetal life, the basement membrane of corneal epithelium and endothelium depicted strong to intense periodic Acid Schiff’s (PAS) reaction. At the irido-corneal angle, the endothelium of blood vessels was also positive for PAS activity. However, cornea was found mild positive for alcian blue reaction. The developing cornea showed strong reaction for basic proteins in outer epithelium and the inner endothelium layers. Under low magnification scanning electron microscope, cornea showed two types of cells viz. light cells and dark cells. The light cells were smaller in size and had less number of microvilli in their surface than in the dark cells. Despite these surface differences between light and dark cells, the corneal surface showed the same general pattern of microvilli studding all exposed surfaces out to the cell margin. which were long (with variable height), slight tortuous slender and possessed a micro villus shaft with a very prominent knob.

Keywords: buffalo, cornea, eye, fetus, ontogeny, scanning electron microscopy

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Authors: Mike T. Wei, Douglas N. Mintz, Lisa A. Mandl, Arielle W. Fein, Jayme C. Burket, Yuo-Yu Lee, Wei-Ti Huang, Vivian P. Bykerk, Mark P. Figgie, Edward F. Di Carlo, Bruce N. Cronstein, Susan M. Goodman

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Background/Purpose: Rheumatoid arthritis (RA) patients have excellent total hip arthroplasty (THA) survival, and methotrexate (MTX), an anti-inflammatory disease modifying drug which may affect bone reabsorption, may play a role. The purpose of this study is to determine the diagnosis leading to revision THA (rTHA) in RA patients and to assess the association of radiographic lucency with MTX use. Methods: All patients with validated diagnosis of RA in the institution’s THA registry undergoing rTHA from May 2007 - February 2011 were eligible. Diagnosis leading to rTHA and medication use was determined by chart review. Osteolysis was evaluated on available radiographs by measuring maximum lucency in each Gruen zone. Differences within RA patients with/without MTX in osteolysis, demographics, and medications were assessed with chi-squared, Fisher's exact tests or Mann-Whitney U tests as appropriate. The error rate for multiple comparisons of lucency in the different Gruen zones was corrected via false discovery rate methods. A secondary analysis was performed to determine differences in diagnoses leading to revision between RA and matched OA controls (2:1 match by sex age +/- 5 years). OA exclusion criteria included presence of rheumatic diseases, use of MTX, and lack of records. Results: 51 RA rTHA were identified and compared with 103 OA. Mean age for RA was 57.7 v 59.4 years for OA (p = 0.240). 82.4% RA were female v 83.5% OA (p = 0.859). RA had lower BMI than OA (25.5 v 28.2; p = 0.166). There was no difference in diagnosis leading to rTHA, including infection (RA 3.9 v OA 6.8%; p = 0.719) or dislocation (RA 23.5 v OA 23.3%; p = 0.975). There was no significant difference in the length of time the implant was in before revision: RA 11.0 v OA 8.8 years (p = 0.060). Among RA with/without MTX, there was no difference in use of biologics (30.0 v 43.3%, p = 0.283), steroids (47.6 v 50.0%, p = 0.867) or bisphosphonates (23.8 v 33.3%, p = 0.543). There was no difference in rTHA diagnosis with/without MTX, including loosening (52.4 v 56.7%, p = 0.762). There was no significant difference in lucencies with MTX use in any Gruen zone. Patients with MTX had femoral stem subsidence of 3.7mm v no subsidence without MTX (p = 0.006). Conclusion: There was no difference in the diagnosis leading to rTHR in RA and OA, although RA trended longer prior to rTHA. In this small retrospective study, there were no significant differences associated with MTX exposure or radiographic lucency among RA patients. The significance of subsidence is not clear. Further study of arthroplasty survival in RA patients is warranted.

Keywords: hip arthroplasty, methotrexate, revision arthroplasty, rheumatoid arthritis

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Authors: Farahnaz Sadat Golestan Hashemi, Mohd Razi Ismail, Mohd Y. Rafii

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A huge revolution has emerged in genome engineering by the discovery of CRISPR (clustered regularly interspaced palindromic repeats) and CRISPR-associated system genes (Cas) in bacteria. The function of type II Streptococcus pyogenes (Sp) CRISPR/Cas9 system has been confirmed in various species. Other S. thermophilus (St) CRISPR-Cas systems, CRISPR1-Cas and CRISPR3-Cas, have been also reported for preventing phage infection. The CRISPR1-Cas system interferes by cleaving foreign dsDNA entering the cell in a length-specific and orientation-dependant manner. The S. thermophilus CRISPR3-Cas system also acts by cleaving phage dsDNA genomes at the same specific position inside the targeted protospacer as observed in the CRISPR1-Cas system. It is worth mentioning, for the effective DNA cleavage activity, RNA-guided Cas9 orthologs require their own specific PAM (protospacer adjacent motif) sequences. Activity levels are based on the sequence of the protospacer and specific combinations of favorable PAM bases. Therefore, based on the specific length and sequence of PAM followed by a constant length of target site for the three orthogonals of Cas9 protein, a well-organized procedure will be required for high-throughput and accurate mining of possible target sites in a large genomic dataset. Consequently, we created a reliable procedure to explore potential gRNA sequences for type I (Streptococcus thermophiles), II (Streptococcus pyogenes), and III (Streptococcus thermophiles) CRISPR/Cas systems. To mine CRISPR target sites, four different searching modes of sgRNA binding to target DNA strand were applied. These searching modes are as follows: i) coding strand searching, ii) anti-coding strand searching, iii) both strand searching, and iv) paired-gRNA searching. The output of such procedure highlights the power of comparative genome mining for different CRISPR/Cas systems. This could yield a repertoire of Cas9 variants with expanded capabilities of gRNA design, and will pave the way for further advance genome and epigenome engineering.

Keywords: CRISPR/Cas systems, gRNA mining, Streptococcus pyogenes, Streptococcus thermophiles

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Authors: Hassan Wajid, Syed T. Ahmed, Syed G. Haider Jr., Razia Latif, Ahsan Ali, Maira Anam

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The phenomenon of Metamorphosis can be associated with any object, organism, or structure gradually and progressively going through the change of systemic or morphological form. This phenomenon can be integrated while teaching drawing to architecture students. In architectural drawings, metamorphosis’s main focus and purpose are not to completely imitate any object. In the process of drawing, the changes in systemic or morphological form happen until the complete process, and the visuals of the complete process change the drawing, opening up possibilities for the imagination of the perceivers. Metamorphosis in architectural drawings begins with an initial form and, through various noticeable stages, ends up final form or manifestation. How much of the initial form is manifested in the final form and progressively among various intermediate stages becomes an indication of the nature of metamorphosis as a phenomenon. It is important at this stage to clarify that the term metamorphosis is presently being coopted from its original domain, usually in life sciences. In this current exercise, the architectural drawings are to act as an operative analog process transforming one image of art and/or architecture in its broadest sense. That composition is claimed to have come from one source (individual work, a cultural artifact, civilizational remain). It dialectically meets, opposes, or confronts some carefully chosen alien opposites from a different domain. As an example, the layers of a detailed drawing of a Turkish prayer rug of 5 x 7 ratio over a detailed architectural plan of a religious, historical complex can be observed such that the two drawings, though at markedly different scales could dialectically converse with one another and through their mutual congruencies. In the final stage, the idea concludes contradictions across the scales to initiate the analogous roles of metamorphosed third reality, which suggests the previous un-acknowledged architectural or artistic identity. The proposed paper explores the trajectory of reproduction by analyzing drawings through detailed drawing stages and analyzes challenges as well as opportunities in the discovered realm of imagination. This description further aims at identifying factors influencing creativity and innovation in producing architectural drawings through the process of observing drawings from inception to the concluding stage.

Keywords: architectural drawings, metamorphosis, perceptions, discovery

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Authors: Jiri Nepereny, Vladimir Vrzal

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Staphylococcus intermedius/pseudintermedius bacteria are commonly found on the skin of healthy dogs and can cause pruritic skin diseases under certain circumstances (trauma, allergy, immunodeficiency, ectoparasitosis, endocrinological diseases, glucocorticoid therapy, etc.). These can develop into complicated superficial or deep pyoderma, which represent a large group of problematic skin diseases in dogs. These are predominantly inflammations of a secondary nature, associated with the occurrence of coagulase-positive Staphylococcus spp. A major problem is increased itching, which greatly complicates the healing process. The aim of this work is to verify the efficacy of the developed preparation Bacteriophage SI (Staphylococcus intermedius). The tested preparation contains a lysate of bacterial cells of S. intermedius host culture including culture medium and live virions of specific phage. Sodium Merthiolate is added as a preservative in a safe concentration. Validation of the efficacy of the product was demonstrated by monitoring the therapeutic effect after application to indicated cases from clinical practice. The indication for inclusion of the patient into the trial was an adequate history and clinical examination accompanied by sample collection for bacteriological examination and isolation of the specific causative agent. Isolate identification was performed by API BioMérieux identification system (API ID 32 STAPH) and rep-PCR typing. The suitability of therapy for a specific case was confirmed by in vitro testing of the lytic ability of the bacteriophage to lyse the specific isolate = formation of specific plaques on the culture isolate on the surface of the solid culture medium. So far, a total of 32 dogs of different sexes, ages and breed affiliations with different symptoms of staphylococcal dermatitis have been included in the testing. Their previous therapy consisted of more or less successful systemic or local application of broad-spectrum antibiotics. The presence of S. intermedius/pseudintermedius has been demonstrated in 26 cases. The isolates were identified as a S. pseudintermedius, in all cases. Contaminant bacterial microflora was always present in the examined samples. The test product was applied subcutaneously in gradually increasing doses over a period of 1 month. After improvement in health status, maintenance therapy was followed by application of the product once a week for 3 months. Adverse effects associated with the administration of the product (swelling at the site of application) occurred in only 2 cases. In all cases, there was a significant reduction in clinical signs (healing of skin lesions and reduction of inflammation) after therapy and an improvement in the well-being of the treated animals. A major problem in the treatment of pyoderma is the frequent resistance of the causative agents to antibiotics, especially the increasing frequency of multidrug-resistant and methicillin-resistant S. pseudintermedius (MRSP) strains. Specific phagolysate using for the therapy of these diseases could solve this problem and to some extent replace or reduce the use of antibiotics, whose frequent and widespread application often leads to the emergence of resistance. The advantage of the therapeutic use of bacteriophages is their bactericidal effect, high specificity and safety. This work was supported by Project FV40213 from Ministry of Industry and Trade, Czech Republic.

Keywords: bacteriophage, pyoderma, staphylococcus spp, therapy

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Authors: Nima Samie, Batoul Sadat Haerian, Sekaran Muniandy, M. S. Kanthimathi

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Colon and breast cancers are categorized as the most prevalent types of cancer worldwide. Recently, the broad clinical application of metal complex compounds has led to the discovery of potential therapeutic drugs. The aim of this study was to evaluate the cytotoxic action of a selected nickel complex compound (NCC) against human colon and breast cancer cells. In this context, we determined the potency of the compound in the induction of apoptosis, cell cycle arrest, and cytoskeleton rearrangement. HT-29, WiDr, CCD-18Co, MCF-7 and Hs 190.T cell lines were used to determine the IC50 of the compound using the MTT assay. Analysis of apoptosis was carried out using immunofluorescence, acridine orange/ propidium iodide double staining, Annexin-V-FITC assay, evaluation of the translocation of NF-kB, oxygen radical antioxidant capacity, quenching of reactive oxygen species content , measurement of LDH release, caspase-3/-7, -8 and -9 assays and western blotting. The cell cycle arrest was examined using flowcytometry and gene expression was assessed using qPCR array. Results showed that our nickel complex compound displayed a potent suppressive effect on HT-29, WiDr, MCF-7 and Hs 190.T after 24 h of treatment with IC50 value of 2.02±0.54, 2.13±0.65, 3.76±015 and 3.14±0.45 µM respectively. This cytotoxic effect on normal cells was insignificant. Dipping in the mitochondrial membrane potential and increased release of cytochrome c from the mitochondria indicated induction of the intrinsic apoptosis pathway by the nickel complex compound. Activation of this pathway was further evidenced by significant activation of caspase 9 and 3/7.The nickel complex compound (NCC) was also shown activate the extrinsic pathways of apoptosis by activation of caspase-8 which is linked to the suppression of NF-kB translocation to the nucleus. Cell cycle arrest in the G1 phase and up-regulation of glutathione reductase, based on excessive ROS production were also observed. The results of this study suggest that the nickel complex compound is a potent anti-cancer agent inducing both intrinsic and extrinsic pathways as well as cell cycle arrest in colon and breast cancer cells.

Keywords: nickel complex, apoptosis, cytoskeletal rearrangement, colon cancer, breast cancer

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Authors: A. K. Faizah, G. Vadamalai, S. K. Balasundram, W. L. Lim

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Pineapple (Ananas comosus) is a common crop in tropical and subtropical areas of the world. Malaysia once ranked as one of the top 3 pineapple producers in the world in the 60's and early 70's, after Hawaii and Brazil. Moreover, government’s recognition of the pineapple crop as one of priority commodities to be developed for the domestics and international markets in the National Agriculture Policy. However, pineapple industry in Malaysia still faces numerous challenges, one of which is the management of disease and pest. Red tip disease on pineapple was first recognized about 20 years ago in a commercial pineapple stand located in Simpang Renggam, Johor, Peninsular Malaysia. Since its discovery, there has been no confirmation on its causal agent of this disease. The epidemiology of red tip disease is still not fully understood. Nevertheless, the disease symptoms and the spread within the field seem to point toward viral infection. Bioassay test on nucleic acid extracted from the red tip-affected pineapple was done on Nicotiana tabacum cv. Coker by rubbing the extracted sap. Localised lesions were observed 3 weeks after inoculation. Negative staining of the fresh inoculated Nicotiana tabacum cv. Coker showed the presence of membrane-bound spherical particles with an average diameter of 94.25nm under transmission electron microscope. The shape and size of the particles were similar to tospovirus. SDS-PAGE analysis of partial purified virions from inoculated N. tabacum produced a strong and a faint protein bands with molecular mass of approximately 29 kDa and 55 kDa. Partial purified virions of symptomatic pineapple leaves from field showed bands with molecular mass of approximately 29 kDa, 39 kDa and 55kDa. These bands may indicate the nucleocapsid protein identity of tospovirus. Furthermore, a handheld sensor, Greenseeker, was used to detect red tip symptoms on pineapple non-destructively based on spectral reflectance, measured as Normalized Difference Vegetation Index (NDVI). Red tip severity was estimated and correlated with NDVI. Linear regression models were calibrated and tested developed in order to estimate red tip disease severity based on NDVI. Results showed a strong positive relationship between red tip disease severity and NDVI (r= 0.84).

Keywords: pineapple, diagnosis, virus, NDVI

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Authors: Guo Lei, Wang Yue, Nakamura Yoshio, Shi Ji

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Recently, perpendicular exchange bias (PEB) is introduced as an active topic attracting continuous efforts. Since its discovery, extrinsic control of PEB has been proposed, due to its scientific significance in spintronic devices and potential application in high density magnetic random access memory with perpendicular magnetic tunneling junction (p-MTJ). To our knowledge, the researches aiming to controlling PEB so far are focused mainly on enhancing the interfacial exchange coupling by adjusting the FM/AFM interface roughness, or optimizing the crystalline structures of FM or AFM layer by employing different seed layers. In present work, the effects of magnetoelastically induced PMA on PEB have been explored in [CoO5nm/CoPt5nm]5 multilayer films. We find the PMA strength of FM layer also plays an important role on PEB at the FM/AFM interface and it is effective to control PEB of [CoO5nm/CoPt5nm]5 multilayer films by changing the magnetoelastically induced PMA of CoPt layer. [CoO5nm/CoPt5nm]5 multilayer films were deposited by magnetron sputtering on fused quartz substrate at room temperature, then annealed at 100°C, 250°C, 300°C and 375°C for 3h, respectively. XRD results reveal that all the samples are well crystallized with preferred fcc CoPt (111) orientation. The continuous multilayer structure with sharp component transition at the CoO5nm/CoPt5nm interface are identified clearly by transmission electron microscopy (TEM), x-ray reflectivity (XRR) and atomic force microscope (AFM). CoPt layer in-plane tensile stress is calculated by sin2φ method, and we find it increases gradually upon annealing from 0.99 GPa (as-deposited) up to 3.02 GPa (300oC-annealed). As to the magnetic property, significant enhancement of PMA is achieved in [CoO5nm/CoPt5nm]5 multilayer films after annealing due to the increase of CoPt layer in-plane tensile stress. With the enhancement of magnetoelastically induced PMA, great improvement of PEB is also achieved in [CoO5nm/CoPt5nm]5 multilayer films, which increases from 130 Oe (as-deposited) up to 1060 Oe (300oC-annealed), showing the same change tendency as PMA and the strong correlation with CoPt layer in-plane tensile stress. We consider it is the increase of CoPt layer in-plane tensile stress that leads to the enhancement of PMA, and thus the enhancement of magnetoelastically induced PMA results in the improvement of PEB in [CoO5nm/CoPt5nm]5 multilayer films.

Keywords: perpendicular exchange bias, magnetoelastically induced perpendicular magnetic anisotropy, CoO5nm/CoPt5nm]5 multilayer film with in-plane stress, perpendicular magnetic tunneling junction

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Authors: Özge Çeliker Tosun, Melda Başer Secer, İsmail Düşmez, Sedat Çapar, İlkay Kozak, Melahat Aktaş, Furkan Can Şimşek, Gökhan Tosun

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Purpose: Portable innovative balance room system with digital game program; It was created to be able to be divided into small areas, such as inside the house, garden, balcony, to enable the person to enter and perform both evaluation and exercise safely, and to ensure that these results can be stored and sent to the therapist live or later when desired. The aim is to compare the effectiveness of the exercise program applied by the elderly within this system and the exercise program implemented under the supervision of a physiotherapist on balance and urinary incontinence symptoms. Materials and Methods: The study was conducted in a randomized controlled manner on 63 people with urinary incontinence (mean age: 75.5 years) at Narlıdere Nursing Home Elderly Care and Rehabilitation Center. Elderly people participating in the study were divided into 3 groups: 1. Group, an exercise program consisting of pelvic floor muscle training and OTOGA exercises, 2. Group, only pelvic floor muscle training, and 3. Group, pelvic floor muscle training and Otoga exercises in the form of a digital game program in a portable balance room system. (self-administered) for 12 weeks. Pelvic floor distress inventory (PTDE-20) and bladder diary were used to evaluate the incontinance symptoms of the cases. Pelvic floor muscle function was evaluated with superficial EMG. Berg, Fall Effectiveness Scale (FES) and Functional Status Evaluations (Chair Stand Test, Eight (8) Food Up and Go Test, Chair Sit and Reach Test, Two Minutes Step Test) were used to evaluate balance. The existence of differences between groups was analyzed using Krusskal Wallis analysis of variance, and the difference between before and after exercise was analyzed with Wilcoxon tests. Results: After treatment, PTDE-20, daily urinary incontinence and toilet visits values decreased significantly in all three groups (p < 0.001). While there was a statistically significant increase in pelvic floor muscle EMG values in the 2nd and third groups after treatment, there was no change in the other group (2nd Group PFM average EMG before-after: 5.5 (4.15-10.95) - 10.95 (8.68-13.68), P=0.05, 3 Group PFM average EMG before-after: 6.5 (4.28-11.55) - 11.75 (8.67-14.26), p=0.04). While BERG score, Chair Stand Test, Eight (8) Food Up and Go Test, and Two Minutes Step Test values increased in all groups (p<0.05), Fall Effectiveness Scale (FES) values did not change after treatment. Conclusion: Although pelvic floor muscle training combined with balance exercises reduces symptoms, it may not lead to a positive improvement in the functions of the pelvic floor muscles. For this reason, recovery lasts for a short time, and then symptoms may reoccur in the future. However, thanks to the new system, when balance exercises are combined with a game program for the pelvic floor muscles, a double effect can be achieved with a single application and both incontinence and balance problems can be treated in a safe environment where the person can do it himself. But more work needs to be done on this subject. However, thanks to the new system, a double effect can be achieved with a single application, and both incontinence and balance problems can be treated in a safe environment where the person can do it himself. But more work needs to be done on new system

Keywords: fall, urinary incontinance, balance, elderly

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Authors: Thomas Suarez, Anne-Sophie Grenouilleau, Erwan Autin, Alexandre Biosse-Duplan, Emmanuelle Blondet, Laurence Chazalette, Marie Coniel, Agnes Dessaigne, Sylvie Lascols, Andrea Lasserre, Candice Legris, Pierre Liot, Aline Metais, Karine Petitprez, Christophe Varlet, Christian Saout

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Background: The role of biological sex and gender identity -whether assigned or chosen- as health determinants are far from a recent discovery: several reports have stressed out how being a woman or a man could affect health on various scales. However, taking it into consideration beyond stereotypes and rigid binary assumptions still seems to be a work in progress. Method: The report is a synthesis on a variety of specific topics, each of which was studied by a specialist from the French National Authority for Health (HAS), through an analysis of existing literature on both healthcare policy construction process and instruments (norms, data analysis, clinical trials, guidelines, and professional practices). This work also implied a policy analysis of French recent public health laws and a retrospective study of guidelines with a gender mainstreaming approach. Results: The analysis showed that though sex and gender were well-known determinants of health, their consideration by both public policy and health operators was often incomplete, as it does not incorporate how sex and gender interact, as well as how they interact with other factors. As a result, the health and social care systems and their professionals tend to reproduce some stereotypical and inadequate habits. Though the data available often allows to take sex and gender into consideration, such data is often underused in practice guidelines and policy formulation. Another consequence is a lack of inclusiveness towards transgender or intersex persons. Conclusions: This report first urges for raising awareness of all the actors of health, in its broadest definition, that sex and gender matter beyond first-look conclusions. It makes a series of recommendations in order to reshape policy construction in the health sector on the one hand and to design public health instruments to make them more inclusive regarding sex and gender on the other hand. The HAS finally committed to integrate sex and gender preoccupations in its workings methods, to be a driving force in the spread of these concerns.

Keywords: biological sex, determinants of health, gender, healthcare policy instruments, social accompaniment

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Authors: Maggie Hui

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Risk management is not a new concept; however, it is an uncharted area as applied to the translation process and translator training. Serving as one of the self-discovery activities in their practicum course, a two-cycle experiment was carried out with a class of 13 MA translation students with an attempt to explore their risk management while translating in a simulated setting that involves translator-client relations. To test the effects of the main variable of translators’ interaction with the simulated clients, the researcher employed control-group translators and two experiment groups (with Group A being the translator in Cycle 1 and the client in Cycle 2, and Group B on the client position in Cycle 1 and the translator position in Cycle 2). Experiment cycle 1 aims to explore if there would be any behavioral difference in risk management between translators with interaction with the simulated clients, i.e. experiment group A, and their counterparts without such interaction, i.e. control group. Design of Cycle 2 concerns the order of playing different roles of the translator and client in the experiment, and provides information to compare behavior of translators of the two experiment groups. Since this is process-oriented research, it is necessary to hypothesize what was happening in the translators’ minds. The researcher made use of a user-friendly screen-voice recording freeware to record subjects’ screen activities, including every word the translator typed and every change they made to the rendition, the websites they browsed and the reference tools they used, in addition to the verbalization of their thoughts throughout the process. The research observes the translation procedures subjects considered and finally adopted, and looks into the justifications for their procedures, in order to interpret their risk management. The qualitative and quantitative results of this study have some implications for translator training: (a) the experience of being a client seems to reinforce the translator’s risk aversion; (b) the use of role-playing simulation can empower students’ learning by enhancing their attitudinal or psycho-physiological competence, interpersonal competence and strategic competence; and (c) the screen-voice recordings serve as a helpful tool for learners to reflect on their rendition processes, i.e. what they performed satisfactorily and unsatisfactorily while translating and what they could do for improvement in future translation tasks.

Keywords: risk management, screen-voice recordings, simulated translator-client relations, translation pedagogy, translation process-oriented research

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Authors: Sara Zelman, Courtney Meyer, Hiren Patel, Lisa Philpotts, Sue Lahey, Thomas Burke

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Background: As the global burden of disease shifts from infectious diseases to noncommunicable diseases, there is growing urgency to provide treatment for time-sensitive illnesses, such as ST-Elevation Myocardial Infarctions (STEMIs). The standard of care for STEMIs in developed countries is Percutaneous Coronary Intervention (PCI). However, this is inaccessible in resource-limited settings. Before the discovery of PCI, Streptokinase (STK) and other thrombolytic drugs were first-line treatments for STEMIs. STK has been recognized as a cost-effective and safe treatment for STEMIs; however, in settings which lack access to PCI, it has not become the established second-line therapy. A systematic literature review was conducted to geographically map the use of STK for STEMIs in resource-limited settings. Methods: Our literature review group searched the databases Cinhal, Embase, Ovid, Pubmed, Web of Science, and WHO’s Index Medicus. The search terms included ‘thrombolytics’ AND ‘myocardial infarction’ AND ‘resource-limited’ and were restricted to human studies and papers written in English. A considerable number of studies came from Latin America; however, these studies were not written in English and were excluded. The initial search yielded 3,487 articles, which was reduced to 3,196 papers after titles were screened. Three medical professionals then screened abstracts, from which 291 articles were selected for full-text review and 94 papers were chosen for final inclusion. These articles were then analyzed and mapped geographically. Results: This systematic literature review revealed that STK has been used for the treatment of STEMIs in 33 resource-limited countries, with 18 of 94 studies taking place in India. Furthermore, 13 studies occurred in Pakistan, followed by Iran (6), Sri Lanka (5), Brazil (4), China (4), and South Africa (4). Conclusion: Our systematic review revealed that STK has been used for the treatment of STEMIs in 33 resource-limited countries, with the highest utilization occurring in India. This demonstrates that even though STK has high utility for STEMI treatment in resource-limited settings, it still has not become the standard of care. Future research should investigate the barriers preventing the establishment of STK use as second-line treatment after PCI.

Keywords: cardiovascular disease, global health, resource-limited setting, ST-Elevation Myocardial Infarction, Streptokinase

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Authors: Victor Counted

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Staying true to self is complicated. In most cases, we might not fully come to terms with this realities. Just like any journey, a self-discovery experience with the ‘self’, is like a rollercoaster ride. The researcher attempts to engage the reader in an empirical study on authenticity tendencies of African Christian Millennials. Hence, attempting the all-important question: What does it actually mean to be true to self for the African youth? A comprehensive, yet an unfinished business that applies the authenticity theory in its exploratory navigations to uncover the “lived world” of the participants who were part of this study. Using a mixed methods approach, the researcher will exhaustively give account to the authenticity tendencies and experiences of the respondents in the study by providing the reader with a unique narrative for understanding what it means to be true to oneself in Africa. At the quantitative study, the participants recorded higher scores on the Authenticity Scale (AS) authentic living, while showing a significant correlation within the subscales. Hypotheses were tested at the quantitative phase, which statistically supported gender and church affiliation as possible predictors for the authenticity orientations of the participants, while being a Christian native and race/ethnicity were not impact factors statistically. The results helped the researcher to develop the objectives behind the qualitative study, where only fifteen AS-authentic living participants were interviewed to understand why they scored high on authentic living, in order to understand what it means to be authentic. The hallmark of the qualitative case study exploration was the common coping mechanism of splitting adopted by the respondents to deal with their self-crisis as they tried to remain authentic to self, whilst self-regulating and self-investing the self to discover ‘self’. Specifically, the researcher observed the concurrent utilization of some kind of the religious-self by the respondents to regulate their self crisis, as they relate with self fragmenting through different splitting stages in hope for some kind of redemption. It was an explanation that led to the conclusion that being authentic is the new pieces. Authenticity is in fragments. This proposition led the researcher to introduce a hermeneutical support-system that will enable future researchers engage more critically and responsibly with their “living human documents” in order to inspire timely solutions that resolve the concerns of authenticity and wellbeing among Millennials in Africa.

Keywords: authenticity, self, identity, self-fragmentation, weak self integration, postmodern self, splitting

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Authors: Paul Shize Li, Frank Alber

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A fundamental task of clinical genomics is to unravel the functions of genes and their associations with disorders. Although experimental biology has made efforts to discover and elucidate the molecular mechanisms of individual genes in the past decades, still about 40% of human genes have unknown functions, not to mention the diseases they may be related to. For those biologists who are interested in a particular gene with unknown functions, a powerful computational method tailored for inferring the functions and disease relevance of uncharacterized genes is strongly needed. Studies have shown that genes strongly linked to each other in multiple biological networks are more likely to have similar functions. This indicates that the densely connected subgraphs in multiple biological networks are useful in the functional and phenotypic annotation of uncharacterized genes. Therefore, in this work, we have developed an integrative network approach to identify the frequent local clusters, which are defined as those densely connected subgraphs that frequently occur in multiple biological networks and consist of the query gene that has few or no disease or function annotations. This is a local clustering algorithm that models multiple biological networks sharing the same gene set as a three-dimensional matrix, the so-called tensor, and employs the tensor-based optimization method to efficiently find the frequent local clusters. Specifically, massive public gene expression data sets that comprehensively cover dynamic, physiological, and environmental conditions are used to generate hundreds of gene co-expression networks. By integrating these gene co-expression networks, for a given uncharacterized gene that is of biologist’s interest, the proposed method can be applied to identify the frequent local clusters that consist of this uncharacterized gene. Finally, those frequent local clusters are used for function and disease annotation of this uncharacterized gene. This local tensor clustering algorithm outperformed the competing tensor-based algorithm in both module discovery and running time. We also demonstrated the use of the proposed method on real data of hundreds of gene co-expression data and showed that it can comprehensively characterize the query gene. Therefore, this study provides a new tool for annotating the uncharacterized genes and has great potential to assist clinical genomic diagnostics.

Keywords: local tensor clustering, query gene, gene co-expression network, gene annotation

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Authors: Laura Struik, Sarah Dow-Fleisner, Robert Janke

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Introduction: The use of e-cigarettes, also known as vaping, has risen exponentially among North American youth and young adults (YYA) in recent years and has become a critical public health concern. The marketing strategies used by e-cigarette companies have been associated with the uptick in use among YYA, with video advertisements on TV and other electronic platforms being the most pervasive strategy. It is unknown if or how these advertisements capitalize on the recently documented multi-faceted influences that contribute to the initiation of vaping among this demographic (e.g., stress, anxiety, gender, peers, etc.), which is examined in this study. Methods: This content analysis is phase one of a two-phased research project that aims to inform meaningful approaches to anti-vaping messaging and campaigns. As part of this first phase, a scoping review has been conducted to identify various influences (environmental, cognitive, contextual, social, and emotional) on e-cigarette uptake among YYA. The results of this scoping review will inform the development of a coding framework to analyze the multiple influences present in vaping advertisements, as seen on two popular television channels (Discovery and AMC). In addition, advertisement characteristics will be incorporated into the coding framework (e.g., the number of people present, demographic details, context, and setting, etc.), and analyzed. Findings: Findings will reveal the types of influences being leveraged in vaping advertisements, and identify the underlying messages that may be particularly attractive to YYA. This will contribute to a more nuanced understanding of how e-cigarette companies market their products and to whom. The results will also inform the next phase of this research project, which will encompass an analysis of anti-vaping advertisements and how the underpinning strategies align with those of the pro-vaping advertisements. Conclusions: Findings of this will study bring forward important implications for developing effective anti-vaping messages, and assist public health professionals in providing more comprehensive prevention and cessation support as it relates to e-cigarette use. Understanding which marketing strategies e-cigarette companies use is vital to our understanding of how to combat them. Findings will inform recommendations for public health efforts aimed at curbing e-cigarette use among YYA, and ultimately contribute to the health and well-being of YYA.

Keywords: e-cigarettes, youth and young adults, advertisements, public health

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Authors: Wayde Veldman, Ozlem T. Bishop, Igor Polikarpov

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In bacteria, mono and disaccharides are phosphorylated during uptake into the cell via the widely used phosphoenolpyruvate (PEP)-dependent phosphotransferase transport system. As an initial step in the phosphorylated disaccharide metabolism pathway, certain glycoside hydrolase family 1 (GH1) enzymes play a crucial role in releasing phosphorylated and non-phosphorylated monosaccharides. However, structural determinants for the specificity of these enzymes still need to be clarified. GH1 enzymes are known to have a wide array of functions. According to the CAZy database, there are twenty-one different enzymatic activities in the GH1 family. Here, the structure and substrate specificity of a GH1 enzyme from Bacillus licheniformis, hereafter known as BlBglH, was investigated. The sequence of the enzyme BlBglH was compared to the sequences of other characterized GH1 enzymes using sequence alignment, sequence identity calculations, phylogenetic analysis, and motif discovery. Through these various analyses, BlBglH was found to have sequence features characteristic of the 6-phospho-β-glucosidase activity enzymes. Additionally, motif and structure comparisons of the three most commonly studied GH1 enzyme-activities revealed a shared loop amongst the different structures that consist of different sequence motifs – this loop is thought to guide specific substrates (depending on activity) towards the active-site. To further affirm BlBglH enzyme activity, molecular docking and molecular dynamics simulations were performed. Docking was carried out using 6-phospho-β-glucosidase enzyme-activity positive (p-Nitrophenyl-beta-D-glucoside-6-phosphate) and negative (p-Nitrophenyl-beta-D-galactoside-6-phosphate) control ligands, followed by 400 ns molecular dynamics simulations. The positive-control ligand maintained favourable interactions within the active site until the end of the simulation. The negative-control ligand was observed exiting the enzyme at 287 ns. Binding free energy calculations showed that the positive-control complex had a substantially more favourable binding energy compared to the negative-control complex. Jointly, the findings of this study suggest that the BlBglH enzyme possesses 6-phospho-β-glucosidase enzymatic activity.

Keywords: 6-P-β-glucosidase, glycoside hydrolase 1, molecular dynamics, sequence analysis, substrate specificity

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Authors: Shivani Dhande, Sanjiv Choudhary, Adarshlata Singh

Abstract:

Introduction: Chemical peeling is a popular, relatively inexpensive day procedure and generally safe method for treatment of pigmentary skin disorders and for skin rejuvenation. Chemical peels are classified by the depth of action into superficial, medium, and deep peels.Various facial pigmentary conditions have significant impact on quality of life causing psychological stress, necessitating its safe and effective treatment.Aim & Objectives:To compare the efficacy of Salicylic acid, Trichloroaceticacid & Glycolic Acid in facial melanosis(melasma,photomelanosis& post acne pigmentation).To study the side effects of above mentioned peeling agents. Method and Materials:It was a randomized parallel control single blind study consisting of total of 36 cases, 12 cases each of melasma, photo melanosis and post acne pigmentation within age group 20-50 years having fitzpatrick’s skin type4. Woods lamp examination was done to confirm the type of melasma.Patients with keloidal tendency, active herpes infection or past history of hypersensitivity to salicylic acid, trichloroaceticand glycolic acid as well aspatients on systemic isotretinoin were excluded.Clinical photographs at the beginning of therapy and then serially, were taken to assess the clinical response. Prior to application a written informed consent was obtained. A post auricular test peel was performed. Patients were divided into 3 groups, containing 12 patients each of melasma, photomelanosis and post acnepigmentation.All the three peels SA peel 20% (done once in 2 weeks), GA peel 50% (done once in 3 weeks) and TCA 15% (done once in 3 weeks) were used with total six settings for each patient. Before application of peel patients were counseled to wash the face with soap and water. Then face was dried and cleaned with spirit and acetone to remove all cutaneous oils. GA, TCA, SA were applied with cotton buds/gauze withmild strokes. After a contact period off 5-10mins neutralization was done with cold water. Post peel topical sunscreen application was mandatory. MASI was used pre and post treatment to assess melasma. Investigator’s global improvement scale- overall hyperpigmentation (4-significant, 3-moderate, 2-mild, 1-minimal, 0-no change ) and Patient’s satisfaction grading scale (>70%- excellent response, 50-70%- good response, <50%- average response) was used to assess improvement in all the three facial melanosis.Results:In our study of 12 patients of melasma, 4 (33.33%)patients showed excellent results;3 (25%) with GAand 1(8.33%) of TCA.Good response was seen in 4 (33.33%) patients;1(8.33%) each for GA & SA and 2(16.66%) for TCA.Poor response was seen in 4(33.33%) patients;1(8.33%) for TCA and 3 (25%) for SA.Of 12 patients of photomelanosis, excellent resultswas seen in 3(25%)patients of TCA. Good response was seen in 4 (33.33%) patients, 1(8.33%) each of TCA &SA and 2(16.66%) of GA.Poor responsewas seen in 5(41.66%) patients;3 (25%) for SA and 2(16.66%) of GA.Of 12 patients of post acne pigmentation, excellent responsein 3 (25%) patients;2(16.66%) of SA and 1(8.33%) of TCA.Good responsewas seen in 5(41.66%) patients;2(16.66%) of SA and GA and1(8.33%) of TCA.Poor response was seen in 4 (33.33%) patients; 2 (16.66%) for SA and TCA both. No major side effects in the form of scarring or persistant pigmentation was seen. Transient blackening of skin with burning sensation was seen in cases treated with TCA and SA. Post procedural itching and redness was noted with GA peel. Conclusion- In our study GA(50%),TCA(15%) & SA(20%) peels showed excellent response in melasma, photomelanosis and post-acne pigmentation respectively.All the 3 peeling agents were well tolerated without any significant side-effects in the above specified concentrations.

Keywords: facial melanosis, gycolic acid, salicylic acid, trichloroacetic acid

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