Search results for: animal identification

Authors: Aoxue Yang, Weili Tian, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and BTSCs. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their regular tissue-resident counterparts. By ribosome profiling analysis, we have identified that glycerol-3-phosphate dehydrogenase 1 (GPD1) is expressed by dormant BTSCs but not by NSCs. Through different stress-induced experiments in vitro, we found that only dexamethasone (DEXA) can significantly increase the expression of GPD1 in NSCs. Adversely, mifepristone (MIFE) which is classified as glucocorticoid receptors antagonists, could decrease GPD1 protein level and weaken the proliferation and stemness in BTSCs. Furthermore, DEXA can induce GPD1 expression in tumor-bearing mice brains and shorten animal survival, whereas MIFE has a distinct adverse effect that prolonged mice lifespan. Knocking out GR in NSC can block the upregulation of GPD1 inducing by DEXA, and we find the specific sequences on GPD1 promotor combined with GR, thus improving the efficiency of GPD1 transcription from CHIP-Seq. Moreover, GR and GPD1 are highly co-stained on GBM sections obtained from patients and mice. All these findings confirmed that GR could regulate GPD1 and loss of GPD1 Impairs Multiple Pathways Important for BTSCs Maintenance GPD1 is also a critical enzyme regulating glycolysis and lipid synthesis. We observed that DEXA and MIFE could change the metabolic profiles of BTSCs by regulating GPD1 to shift the transition of cell dormancy. Our transcriptome and lipidomics analysis demonstrated that cell cycle signaling and phosphoglycerides synthesis pathways contributed a lot to the inhibition of GPD1 caused by MIFE. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and contribute to BTSC dormancy. Inhibition of GR can dramatically reduce GPD1 and extend the survival duration of GBM-bearing mice. The molecular link between GPD1 and GR may give us an attractive therapeutic target for glioblastoma.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides

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Authors: Shivangi Somvanshi

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Poor crop productivity in salt-affected environment in the country is due to insufficient and untimely canal supply to agricultural land and inefficient field water management practices. This could further degrade due to inadequate maintenance of canal network, ongoing secondary soil salinization and waterlogging, worsening of groundwater quality. Large patches of low productivity in irrigation commands are occurring due to waterlogging and salt-affected soil, particularly in the scarcity rainfall year. Satellite remote sensing has been used for mapping of areas of low crop productivity, waterlogging and salt in irrigation commands. The spatial results obtained for these problems so far are less reliable for further use due to rapid change in soil quality parameters over the years. The existing spatial databases of canal network and flow data, groundwater quality and salt-affected soil were obtained from the central and state line departments/agencies and were integrated with GIS. Therefore, an integrated methodology based on remote sensing and GIS has been developed in ArcGIS environment on the basis of canal supply status, groundwater quality, salt-affected soils, and satellite-derived vegetation index (NDVI), salinity index (NDSI) and waterlogging index (NSWI). This methodology was tested for identification and delineation of area of low productivity in the Gautam Buddha Nagar district (Uttar Pradesh). It was found that the area affected by this problem lies mainly in Dankaur and Jewar blocks of the district. The problem area was verified with ground data and was found to be approximately 78% accurate. The methodology has potential to be used in other irrigation commands in the country to obtain reliable spatial data on low crop productivity.

Keywords: remote sensing, GIS, salt affected soil, crop productivity, Gautam Buddha Nagar

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Authors: Rumaisa Shahid, Saad Aziz Durrani, Shameel Pervez, Ibatsam Khokhar

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Food waste is a prevalent issue in Pakistan, with over 40 percent of food discarded annually. Despite their decay, rotting fruits retain residual nutritional value consumed by microorganisms, notably fungi and bacteria. Fungi, preferred for their extracellular enzyme release, are gaining prominence, particularly for pectinase production. This enzyme offers several advantages, including clarifying juices by breaking down pectic compounds. In this study, three Aspergillus flavus isolates derived from decomposed fruits and manure were selected for pectinase production. The primary aim was to isolate fungi from diverse waste sources, identify the isolates and assess their capacity for pectinase production. The identification was done through morphological characteristics with the help of Light microscopy and Scanning Electron Microscopy (SEM). Pectinolytic potential was screened using pectin minimal salt agar (PMSA) medium, comparing clear zone diameters among isolates. Identification relied on morphological characteristics. Optimizing substrate (lemon and orange peel powder) concentrations, pH, temperature, and incubation period aimed to enhance pectinase yield. Spectrophotometry enabled quantitative analysis. The temperature was set at room temperature (28 ºC). The optimal conditions for Aspergillus flavus strain AF1(isolated from mango) included a pH of 5, an incubation period of 120 hours, and substrate concentrations of 3.3% for orange peels and 6.6% for lemon peels. For AF2 and AF3 (both isolated from soil), the ideal pH and incubation period were the same as AF1 i.e. pH 5 and 120 hours. However, their optimized substrate concentrations varied, with AF2 showing maximum activity at 3.3% for orange peels and 6.6% for lemon peels, while AF3 exhibited its peak activity at 6.6% for orange peels and 8.3% for lemon peels. Among the isolates, AF1 demonstrated superior performance under these conditions, comparatively.

Keywords: pectinase, lemon peel, orange peel, aspergillus flavus

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Authors: Cyril Kaplan

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26 participants played 4 EEG neurofeedback (NF) games encouraged to find their strategies to control the specific NF parameter. Mixed method analysis of performance in the games and post-session interviews led to the identification of states of consciousness that correlated with success in the game. We found that increase in left frontal beta activity was facilitated by evoking interest in observed surroundings, by wondering what is happening behind the window or what lies in a drawer in front.

Keywords: EEG neurofeedback, states of consciousness, frontal beta activity, mixed methods

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Authors: Jill Steel

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The interlinked issues of emotional wellbeing and attainment continue to dominate international educational discourse. Reading skills are particularly important to attainment in all areas of the curriculum, and illiteracy is associated with reduced wellbeing and life prospects, with serious ramifications for the wider economy and society. Research shows that reading attainment is influenced by reading motivation and frequency. Reading to Dogs (RTD) is increasingly applied to promote reading motivation and frequency in schools despite a paucity of empirical evidence, specifically examining the influence of RTD on emotional wellbeing and engagement with reading. This research aims to examine whether RTD is effective in promoting these positive outcomes among children aged eight to nine years. This study also aims to inform much needed regulation of the field and standards of practice, including both child and dog welfare. Therefore, ethical matters such as children’s inclusion and safety, as well as the rights and wellbeing of dogs infuse the study throughout. The methodological design is a mixed method longitudinal study. A UK wide questionnaire will be distributed to teachers between January and June 2020 to understand their perceptions of RTD. Following this, a randomised controlled trial (N = 100) will begin in August 2020 in two schools of a comparable demographic, with N= 50 in the intervention school, and N= 50 in a waiting list control school. Reading and wellbeing assessments will be conducted prior to and immediately post RTD, and four weeks after RTD to measure sustained changes. The reading assessments include New Group Reading Test, Motivation to Read Profile (Gambrell et al., 1995), as well as reading frequency and reading anxiety assessments specifically designed for the study. Wellbeing assessments include Goodman’s SDQ, (1997) and pupil self-reporting questionnaires specifically designed for the study. Child, class teacher, and parent questionnaires and interviews prior to, during and post RTD will be conducted to measure perceptions of the impact of RTD on mood and motivation towards reading. This study will make a substantial contribution to our understanding of the effectiveness of RTD and thus have consequences for the fields of education and anthrozoology.

Keywords: animal assisted intervention, reading to dogs, welfare, wellbeing

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Authors: Mrinal Gupta, Mohammad Rumman, Babita Singh Abbas Ali Mahdi, Shivani Pandey

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Introduction: Berberine (BBR), a bioactive compound isolated from Coptidis Rhizoma, possesses diverse pharmacological activities, including anti-bacterial, anti-inflammatory, antitumor, hypolipidemic, and anti-diabetic. However, its role as an anti-diabetic agent in animal models of dexamethasone (Dex)-induced diabetes remains unknown. Studies have shown that natural compounds, including aloe, caper, cinnamon, cocoa, green and black tea, and turmeric, can be used for treating Type 2 diabetes mellitus (DM). Compared to conventional drugs, natural compounds have fewer side effects and are easily available. Herein, we studied the anti-diabetic effects of BBR in a mice model of Dex-induced diabetes. Methods: HepG2 cell line was used for glucose release and glycogen synthesis studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. For animal studies, mice were treated with Dex (2 mg/kg, i.m.) for 30 days and the effect of BBR at the doses 100, 200, and 500 mg/kg (p.o.) was analyzed. Glucose, insulin, and pyruvate tests were performed to evaluate the development of the diabetic model. An echo MRI was performed to assess the fat mass. Further, to elucidate the mechanism of action of BBR, mRNA expression of genes regulating gluconeogenesis, glucose uptake, and glycolysis were analyzed. Results: In vitro BBR had no impact on cell viability up to a concentration of 50μM. Moreover, BBR suppressed the hepatic glucose release and improved glucose tolerance in HepG2 cells. In vivo, BBR improved glucose homeostasis in diabetic mice, as evidenced by enhanced glucose clearance, increased glycolysis, elevated glucose uptake, and decreased gluconeogenesis. Further, Dex treatment increased the total fat mass in mice, which was ameliorated by BBR treatment. Conclusion: BBR improves glucose tolerance by increasing glucose clearance, inhibiting hepatic glucose release, and decreasing obesity. Thus, BBR may become a potential therapeutic agent for treating glucocorticoid-induced diabetes and obesity in the future.

Keywords: glucocorticoid, hyperglycemia, berberine, HepG2 cells, insulin resistance, glucose

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Authors: Brittany L. Kang

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One familiar theory of the origin of multiple personalities focuses on how symptoms of trauma or abuse are central causes, as seen in paradigmatic examples of the condition. The theory states that multiple personalities constitute a congenital condition, as babies all exhibit multiplicity, and that generally alters only remain separated due to trauma. In more typical cases, the alters converge and become a single identity; only in cases of trauma, according to this account, do the alters remain separated. This theory is misleading in many aspects, the most prominent being that not all multiple personality patients are victims of child abuse or trauma, nor are all cases of multiple personality observed in early childhood. The use of this criterion also causes clinical problems, including an inability to identify multiple personalities through the variety of symptoms and traits seen across observed cases. These issues present a need for revision in the currently applied criterion in order to separate the notion of child abuse and to be able to better understand the origins of multiple personalities itself. Identifying multiplicity through the application of identity theories will improve the current criterion, offering a bridge between identifying existing cases and understanding their origins. We begin by applying arguments from Wiggins, who held that each personality within a multiple was not a whole individual, but rather characters who switch off. Wiggins’ theory is supported by observational evidence of how such characters are differentiated. Alters of older ages are seen to require different prescription lens, in addition to having different handwriting. The alters may also display drastically varying styles of clothing, preferences in food, their gender, sexuality, religious beliefs and more. The definitions of terms such as 'personality' or 'persons' also become more distinguished, leading to greater understanding of who is exactly able to be classified as a patient of multiple personalities. While a more common meaning of personality is a designation of specific characteristics which account for the entirety of a person, this paper argues from Wiggins’ theory that each 'personality' is in fact only partial. Clarification of the concept in question will allow for more successful future clinical applications.

Keywords: identification, multiple personalities, origin, Wiggins' theory

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Authors: Mahmoud Huleihel, George Abu-Aqil, Manal Suleiman, Klaris Riesenberg, Itshak Lapidot, Ahmad Salman

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Urinary tract infections (UTIs) are considered to be the most common bacterial infections worldwide, which are caused mainly by Escherichia (E.) coli (about 80%). Klebsiella pneumoniae (about 10%) and Pseudomonas aeruginosa (about 6%). Although antibiotics are considered as the most effective treatment for bacterial infectious diseases, unfortunately, most of the bacteria already have developed resistance to the majority of the commonly available antibiotics. Therefore, it is crucial to identify the infecting bacteria and to determine its susceptibility to antibiotics for prescribing effective treatment. Classical methods are time consuming, require ~48 hours for determining bacterial susceptibility. Thus, it is highly urgent to develop a new method that can significantly reduce the time required for determining both infecting bacterium at the species level and diagnose its susceptibility to antibiotics. Fourier-Transform Infrared (FTIR) spectroscopy is well known as a sensitive and rapid method, which can detect minor molecular changes in bacterial genome associated with the development of resistance to antibiotics. The main goal of this study is to examine the potential of FTIR spectroscopy, in tandem with machine learning algorithms, to identify the infected bacteria at the species level and to determine E. coli susceptibility to different antibiotics directly from patients' urine in about 30minutes. For this goal, 1600 different E. coli isolates were isolated for different patients' urine sample, measured by FTIR, and analyzed using different machine learning algorithm like Random Forest, XGBoost, and CNN. We achieved 98% success in isolate level identification and 89% accuracy in susceptibility determination.

Keywords: urinary tract infections (UTIs), E. coli, Klebsiella pneumonia, Pseudomonas aeruginosa, bacterial, susceptibility to antibiotics, infrared microscopy, machine learning

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Authors: Alexander A. Tokmakov

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Cell-free protein synthesis is widely used to synthesize recombinant proteins. It allows genome-scale expression of various polypeptides under strictly controlled uniform conditions. However, only a minor fraction of all proteins can be successfully expressed in the systems of protein synthesis that are currently used. The factors determining expression success are poorly understood. At present, the vast volume of data is accumulated in cell-free expression databases. It makes possible comprehensive bioinformatics analysis and identification of multiple features associated with successful cell-free expression. Here, we describe an approach aimed at identification of multiple physicochemical and structural properties of amino acid sequences associated with protein solubility and aggregation and highlight major correlations obtained using this approach. The developed method includes: categorical assessment of the protein expression data, calculation and prediction of multiple properties of expressed amino acid sequences, correlation of the individual properties with the expression scores, and evaluation of statistical significance of the observed correlations. Using this approach, we revealed a number of statistically significant correlations between calculated and predicted features of protein sequences and their amenability to cell-free expression. It was found that some of the features, such as protein pI, hydrophobicity, presence of signal sequences, etc., are mostly related to protein solubility, whereas the others, such as protein length, number of disulfide bonds, content of secondary structure, etc., affect mainly the expression propensity. We also demonstrated that amenability of polypeptide sequences to cell-free expression correlates with the presence of multiple sites of post-translational modifications. The correlations revealed in this study provide a plethora of important insights into protein folding and rationalization of protein production. The developed bioinformatics approach can be of practical use for predicting expression success and optimizing cell-free protein synthesis.

Keywords: bioinformatics analysis, cell-free protein synthesis, expression success, optimization, recombinant proteins

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Authors: Mohamed El Kory Yacoub, Ahmed Bezeid El Mamy Beyatt, Djibril Barry, Yanogo Pauline, Nicolas Meda

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Introduction: Rift Valley Fever is a zoonotic arbovirosis that severely affects ruminants, as well as humans. It causes abortions in pregnant females and deaths in young animals. The disease occurs during heavy rains followed by large numbers of mosquito vectors. The objective of this work is to evaluate the surveillance system for Rift Valley Fever. Methods: We conducted an evaluation of the Rift Valley Fiver surveillance system. Data were collected from the analysis of the national database of the Mauritanian Network of Animal Disease Epidemiological Surveillance at the Ministry of Rural Development, of RVF cases notified from the whole national territory, of questionnaires and interviews with all persons involved in RVF surveillance at the central level. The quality of the system was assessed by analyzing the quantitative attributes defined by the Centers for Disease Control and Prevention. Results: In 2019, 443 cases of RVF were notified by the surveillance system, of which 36 were positive. Among the notified cases of Rift Valley Fever, the 0- to the 3-year-old age group of small ruminants was the most represented with 49.21% of cases, followed by 33.33%, which was recorded in large ruminants in the 0 to 7-year-old age group, 11.11% of cases were older than seven years. The completeness of the data varied between 14.2% (age) and 100% (species). Most positive cases were recorded between October and November 2019 in seven different regions. Attribute analysis showed that 87% of the respondents were able to use the case definition well, and 78.8% said they were familiar with the reporting and feedback loop of the Rift Valley Fever data. 90.3% of the respondents found it easy, while 95% of them responded that it was easy for them to transmit their data to the next level. Conclusions: The epidemiological surveillance system for Rift Valley Fever in Mauritania is simple and representative. However, data quality, stability, and responsiveness are average, as the diagnosis of the disease requires laboratory confirmation and the average delay for this confirmation is long (13 days). Consequently, the lack of completeness of the recorded data and of description of cases in terms of time-place-animal, associated with the delay between the stages of the surveillance system can make prevention, early detection of epidemics, and the initiation of measures for an adequate response difficult.

Keywords: evaluation, epidemiological surveillance system, rift valley fever, mauritania, ruminants

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Authors: Nobuyuki Takemoto, Ai Koyanagi, Masanori Yasuda, Hiroshi Yamamoto

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Background: Fluorescence imaging (FI) is one of the methods to identify sentinel lymph nodes (SLNs). However, the procedure is technically complicated and requires procedural skills, as SLN biopsy must be conducted in dim light conditions. As an improved version of this method, we introduced a combined method (Combined mixed dye and fluorescence; CMF) consisting of indigo carmine blue dye and FI. The direct visualization of SLNs under shadowless surgical light conditions is facilitated by the addition of the blue dye. We compared the SLN detection rates of CMF with that of the indocyanine green (ICG) dye method (ICG-D). Methods: A total of 202 patients with stage ≤ IIA breast cancer who underwent breast conservative therapy with separate incision from January 2004 to February 2017 were reviewed. Details of the two methods are as follows: (1) ICG-D: 2ml of ICG (10mg) was used and the green-stained SLNs were resected via a 3-4cm axillary incision; (2) CMF: A combination of 1ml of ICG (5mg) and 1-3ml of indigo carmine (4-12mg) was used. Using Photodynamic Eye (PDE), a 1.5-2 cm incision was made near the point of disappearance of the fluorescence and SLNs with intermediate color of blue and green were resected. Results: There were 92 ICG-D and 110 CMF cases. CMF resulted in a significantly higher detection rate than ICG-D (96.4% vs. 83.7%; p=0.003). This difference was particularly notable in those aged ≥ 60 years (98.3% vs. 74.3%) and individuals with BMI ≥ 25kg/m2 (90.3% vs. 58.3%). Conclusion: CMF is an effective method to identify SLNs which is safe, efficient, and cost-effective. Furthermore, radiation exposure can be avoided, and it can be performed in institutes without nuclear medicine facilities. CMF achieves a high SLN identification rate, and most of this procedure is feasible under shadowless surgical light conditions. CMF can reliably perform SLN biopsy even in those aged ≥ 60 years and individuals with BMI ≥ 25 kg/m2.

Keywords: sentinel lymph node biopsy, identification rate, indocyanine green (ICG), indigocarmine, fluorescence

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Authors: Yasser Sanad, Thu Trang Dao

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Introduction: Implementing the One Health (OH) approach requires an integrated, interdisciplinary, and cross-sectoral methodology. OH is a key tool for developing and implementing programs and projects and includes developing ambitious policies that consider the common needs and benefits of human, animal, plant, and ecosystem health. OH helps humanity readjust its path to environmentally friendly and impartial sustainability. As co-leader of the Global Health Security Agenda’s Zoonotic Disease Action Package, Vietnam pioneered a strong OH approach to effectively address early waves of the COVID-19 outbreak in-country. Context and Aim: The repeated surges in COVID-19 in Vietnam challenged the capabilities of the national system and disclosed the gaps in multi-sectoral coordination and resilience. To address this, FHI 360 advocated for the standardization of the OH platform by government actors to increase the resiliency of the system during and post COVID-19. Methods: FHI 360 coordinated technical resources to develop and implement evidence-based OH policies, promoting high-level policy dialogue between the Ministries of Health, Agriculture, and the Environment, and policy research to inform developed policies and frameworks. Through discussions, an OH-building Partnership (OHP) was formed, linking climate change, the environment, and human and animal health. Findings: The OHP Framework created a favorable policy environment within and between sectors, as well as between governments and international health security partners. It also promoted strategic dialogue, resource mobilization, policy advocacy, and integration of international systems with National Steering Committees to ensure accountability and emphasize national ownership. Innovative contribution to policy, practice and/or research: OHP was an effective evidence-based research-to-policy platform linking to the National One Health Strategic Plan (2021-2025). Collectively they serve as a national framework for the implementation and monitoring of OH activities. Through the adoption of policies and plans, the risk of zoonotic pathogens, environmental agent spillover, and antimicrobial resistance can be minimized through strengthening multi-sectoral OH collaboration for health security.

Keywords: one health, national policies, health security, COVID-19, Vietnam

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Authors: Aurora Gitto, Philipp Proksch

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The presence of various microorganisms (bacteria, fungi) in surface water and groundwater represents an important issue for human health worldwide. The matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) has emerged as a promising and reliable tool for bacteria identification in clinical diagnostic microbiology and environmental strains thanks to an ionization technique that uses a laser energy absorbing matrix to create ions from large molecules with minimal fragmentation. The study aims first to conceptualise and set up library information and create a comprehensive database of MALDI-TOF-MS spectra from environmental water samples. The samples were analysed over a year (2021-2022) using membrane filtration methodology (0.45 μm and 0.22 μm) and then isolated on R2A agar for a period of 5 days and Yeast extract agar growing at 22 °C up to 4 days and 37 °C for 48 hours. The undetected organisms by MALDI-TOF-MS were analysed by PCR and then sequenced. The information obtained by the sequencing was further implemented in the MALDI-TOF-MS library. Among the culturable bacteria, the results show how the incubator temperature affects the growth of some genera instead of others, as demonstrated by Pseudomonas sp., which grows at 22 °C, compared to Bacillus sp., which is abundant at 37 °C. The bacteria community shows a variation in composition also between the media used, as demonstrated with R2A agar which has been defined by a higher presence of organisms not detected compared to YEA. Interesting is the variability of the Genus over one year of sampling and how the seasonality impacts the bacteria community; in fact, in some sampling locations, we observed how the composition changed, moving from winter to spring and summer. In conclusion, the bacteria community in groundwater and river bank filtration represents important information that needs to be added to the library to simplify future water quality analysis but mainly to prevent potential risks to human health.

Keywords: water quality, MALDI-TOF-MS, sequencing, library

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Authors: Peter David Reiss

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The concept of the psychosis prodrome has allowed for the identification of adolescent and young adult patients who have a significantly elevated risk of developing schizophrenia spectrum disorders. A number of different interventions have been tested in order to prevent or delay progression of symptoms. To date, there has been no consistent meta-analytical evidence to support efficacy of antipsychotic treatment for patients in the prodromal state, and their use remains therefore inconclusive. Although antipsychotics may manage symptoms transiently, they have not been found to prevent or delay onset of psychotic disorders. Furthermore, pharmacological intervention in high-risk individuals remains controversial, because of the antipsychotic side effect profile in a population in which only about 20 to 35 percent will eventually convert to psychosis over a two-year period, with even after two years conversion rates not exceeding 30 to 40 percent. This general estimate is additionally problematic, in that it ignores the fact that there is significant variation in individual risk among clinical high-risk cases. The current lack of reliable tests for at-risk patients makes it difficult to justify individual treatment decisions. Preventive treatment should ideally be dictated by an individual’s risk while minimizing potentially harmful medication exposure. This requires more accurate predictive assessments by using valid and accessible prognostic markers. The following will compare prediction and risk modification potential of behavioral biomarkers such as disturbances of basic sense of self and emotion awareness, neurocognitive biomarkers such as attention, working and declarative memory, and neurophysiological biomarkers such as glutamatergic abnormalities and NMDA receptor dysfunction. Identification of robust biomarkers could therefore not only provide more reliable means of psychosis prediction, but also help test and develop new clinical interventions targeted at the prodromal state.

Keywords: at-risk mental state, biomarkers, glutamatergic system, NMDA receptor, psychosis prodrome, schizophrenia

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Authors: Matheus Madureira Matos, Alexandre Rodrigues Farias

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Magnetic Resonance Imaging (MRI) is a vital imaging technique used in both clinical and pre-clinical areas to obtain detailed anatomical and functional information. However, MRI scans can be expensive, time-consuming, and often require the use of anesthetics to keep animals still during the imaging process. Anesthetics are commonly administered to animals undergoing MRI scans to ensure they remain still during the imaging process. However, prolonged or repeated exposure to anesthetics can have adverse effects on animals, including physiological alterations and potential toxicity. Minimizing the duration and frequency of anesthesia is, therefore, crucial for the well-being of research animals. In recent years, various sampling trajectories have been investigated to reduce the number of MRI measurements leading to shorter scanning time and minimizing the duration of animal exposure to the effects of anesthetics. Compressed sensing (CS) and sampling trajectories, such as cartesian, spiral, and radial, have emerged as powerful tools to reduce MRI data while preserving diagnostic quality. This work aims to apply CS and cartesian, spiral, and radial sampling trajectories for the reconstruction of MRI of the abdomen of mice sub-sampled at levels below that defined by the Nyquist theorem. The methodology of this work consists of using a fully sampled reference MRI of a female model C57B1/6 mouse acquired experimentally in a 4.7 Tesla MRI scanner for small animals using Spin Echo pulse sequences. The image is down-sampled by cartesian, radial, and spiral sampling paths and then reconstructed by CS. The quality of the reconstructed images is objectively assessed by three quality assessment techniques RMSE (Root mean square error), PSNR (Peak to Signal Noise Ratio), and SSIM (Structural similarity index measure). The utilization of optimized sampling trajectories and CS technique has demonstrated the potential for a significant reduction of up to 70% of image data acquisition. This result translates into shorter scan times, minimizing the duration and frequency of anesthesia administration and reducing the potential risks associated with it.

Keywords: compressed sensing, magnetic resonance, sampling trajectories, small animals

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Authors: Charmi Chande, Ravindra Phadke

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Microfluidics devices are fabricated by using multiple fabrication methods. Photolithography is one of the common methods wherein SU8 is widely used for making master which in turn is used for making working chip by the process of soft lithography. The high-aspect ratio features of SU-8 makes it suitable to be used as micro moulds for injection moulding, hot embossing, and moulds to form polydimethylsiloxane (PDMS) structures for bioMEMS (Microelectromechanical systems) applications. But due to high cost, difficulty in procuring and need for clean room, restricts the use of this polymer especially in developing countries and small research labs. ‘Bisphenol –A’ based polymers in mixture with curing agent are used in various industries like Paints and coatings, Adhesives, Electrical systems and electronics, Industrial tooling and composites. We present the novel use of ‘Bisphenol – A’ based polymer in fabricating micro channels for Lab On Chip(LOC) devices. The present paper describes the prototype for production of microfluidics chips using range of ‘Bisphenol-A’ based polymers viz. GY 250, ATUL B11, DER 331, DER 330 in mixture with cationic photo initiators. All the steps of chip production were carried out using an inexpensive approach that uses low cost chemicals and equipment. This even excludes the need of clean room. The produced chips using all above mentioned polymers were validated with respect to height and the chip giving least height was selected for further experimentation. The lowest height achieved was 7 micrometers by GY250. The cost of the master fabricated was $ 0.20 and working chip was $. 0.22. The best working chip was used for morphological identification and profiling of microorganisms from environmental samples like soil, marine water and salt water pan sites. The current chip can be adapted for various microbiological screening experiments like biochemical based microbial identification, studying uncultivable microorganisms at single cell/community level.

Keywords: bisphenol–A based epoxy, cationic photoinitiators, microfabrication, photolithography

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Authors: Michaela Storen, Michelle Harvey, Xavier Conlan

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Gun violence internationally is increasing at an unprecedented level, becoming a favoured means for executing violence against another individual. Not only is this putting a strain on forensic scientists who attempt to determine the cause of death in circumstances where firearms have been involved in the death of an individual, but it also highlights the need for an alternative technique of identification of a gunshot wound when other established techniques have been exhausted. A corpse may be colonized by necrophagous insects following death, and this close association between the time of death and insect colonization makes entomological samples valuable evidence when remains become decomposed beyond toxicological utility. Entomotoxicology provides the potential for the identification of toxins in a decomposing corpse, with recent research uncovering the capabilities of entomotoxicology to detect gunshot residue (GSR) in a corpse. However, shortcomings of the limited literature available on this topic have not been addressed, with the bioaccumulation, detection limits, and sensitivity to gunshots not considered thus far, leaving questions as to the applicability of this new technique in the forensic context. Larvae were placed on meat contaminated with GSR at different concentrations and compared to a control meat sample to establish the uptake of GSR by the larvae, with bioaccumulation established by placing the larvae on fresh, uncontaminated meat for a period of time before analysis using ICP-MS. The findings of Pb, Ba, and Sb at each stage of the lifecycle and bioaccumulation in the larvae will be presented. In addition, throughout these previously mentioned experiments, larvae were washed once, twice and three times to evaluate the effectiveness of existing entomological practices in removing external toxins from specimens prior to entomotoxicologyical analysis. Analysis of these larval washes will be presented. By addressing these points, this research extends the utility of entomotoxicology in cause-of-death investigations and provides an additional source of evidence for forensic scientists in the circumstances involving a gunshot wound on a corpse, in addition to advising the effectiveness of current entomology collection protocols.

Keywords: bioaccumulation, chemistry, entomology, gunshot residue, toxicology

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Authors: Muhamad Hafiz Ismail, Ahmad H., Nelfianty M. R.

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The longitudinal study is conducted to identify predictive factors of soccer talent among male players aged 14 to 17 years. Convenience sampling involving elite respondents (n=20) and sub-elite respondents (n=20) male soccer players. Descriptive statistics were reported as frequencies and percentages. The inferential statistical analysis is used to report the status of reliability, independent samples t-test, paired samples t-test, and multiple regression analysis. Generally, there are differences in mean of height, muscular strength, muscular endurance, cardiovascular endurance, task orientation, cognitive anxiety, self-confidence, juggling skills, short pass skills, long pass skills, dribbling skills, and shooting skills for 20 elite players and sub-elite players. Accordingly, there was a significant difference between pre and post-test for thirteen variables of height, weight, fat percentage, muscle strength, muscle endurance, cardiovascular endurance, flexibility, BMI, task orientation, juggling skills, short pass skills, a long pass skills, and dribbling skills. Based on the first predictive factors (physical), second predictive factors (fitness), third predictive factors (psychological), and fourth predictive factors (skills in playing football) pledged to the soccer talent; four multiple regression models were produced. The first predictive factor (physical) contributed 53.5 percent, supported by height and percentage of fat in soccer talents. The second predictive factor (fitness) contributed 63.2 percent and the third predictive factors (psychology) contributed 66.4 percent of soccer talent. The fourth predictive factors (skills) contributed 59.0 percent of soccer talent. The four multiple regression models could be used as a guide for talent scouting for soccer players of the future.

Keywords: soccer talent identification, fitness and physical test, soccer skills test, psychological test

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Authors: Awais Ahmed, Javed Iqbal

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Pakistan has been for many years facing extreme challenges in energy deficit due to the shortage of power generation compared to increasing demand. A part of this energy deficit is also contributed by the power lost in transmission and distribution network. Unfortunately, distribution companies are not equipped with modern technologies and methods to identify and eliminate these losses. According to estimate, total energy lost in early 2000 was between 20 to 26 percent. To address this issue the present research study was designed with the objectives of developing a standalone GIS application for distribution companies having the capability of loss calculation as well as identification of overloaded transformers. For this purpose, Hilal Road feeder in Faisalabad Electric Supply Company (FESCO) was selected as study area. An extensive GPS survey was conducted to identify each consumer, linking it to the secondary pole of the transformer, geo-referencing equipment and documenting conductor sizes. To identify overloaded transformer, accumulative kWH reading of consumer on transformer was compared with threshold kWH. Technical losses of 11kV and 220V lines were calculated using the data from substation and resistance of the network calculated from the geo-database. To automate the process a standalone GIS application was developed using ArcObjects with engineering analysis capabilities. The application uses GIS database developed for 11kV and 220V lines to display and query spatial data and present results in the form of graphs. The result shows that about 14% of the technical loss on both high tension (HT) and low tension (LT) network while about 4 out of 15 general duty transformers were found overloaded. The study shows that GIS can be a very effective tool for distribution companies in management and planning of their distribution network.

Keywords: geographical information system, GIS, power distribution, distribution transformers, technical losses, GPS, SDSS, spatial decision support system

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Authors: J. M. Hernández-Ontiveros, E. E. García-Guerrero, E. Inzunza-González, O. R. López-Bonilla

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This paper presents the implementation of an algorithm that identifies and accounts different fish species: Catfish, Sea bream, Sawfish, Tilapia, and Totoaba. The main contribution of the method is the fusion of the characteristics of invariance to the position, rotation and scale of the Hu moments, with the proper counting of fish. The identification and counting is performed, from an image under different noise conditions. From the experimental results obtained, it is inferred the potentiality of the proposed algorithm to be applied in different scenarios of aquaculture production.

Keywords: counting fish, digital image processing, invariant moments, pattern recognition

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Authors: B. Bakchiche, H. Guenane, M. Bireche, A. Noureddinne, A. Gherib

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The chemical composition of the essential oils obtained by hydrodistillation from Artemisia campestris L (family Asteraceae) collected in Djebel Amour (Sahara Atlas, Algeria). Aerial parts were also evaluated by gas chromatography (GC) and gas chromatography coupled to mass spectrometry (GC-MS). The analyses for leaves and fruits of A. campestris resulted in the identification of thirty-one compounds, representing 91.8 % of the total oil and the yields were 0.33% (v/dry weight). The main components were β-pinene and sabinene (25.6% and 17% respectively) followed by α-pinene (9.9%), limonene (6.6 %) and p-cymene (4.1%).

Keywords: essential oil, GC-MS, Artemesia campestris, Algeria

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Authors: Shazia Naheed Akhter, Rekha Kumari

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An estimated 70 million population are exposed to arsenic poisoning in India in recent times. Arsenic contamination in the groundwater has caused serious health hazards among the exposed population. In Bihar, the first district was Bhojpur, where arsenic causing health issues were reported in 2002. Presently, there are 18 districts that are reported arsenic poisoning in the groundwater. The exposed population is firstly diseased with various symptoms such as skin manifestations, loss of appetite, constipation, hormonal disorders, etc. The long duration exposure has led to cause infertility in the male subjects. The present study thus aims to develop the antidote against arsenic-induced male reproductive toxicity in animal models. The study was carried out on Charles Foster Rats after the approval from Institutional Animal Ethics Committee. A total of n=18 rats (12 weeks old) of an average weight of 160 ± 20 g were used for the study. The study group included n=6 control and n= 12 treated with sodium arsenite orally at the dose of 8mg/Kg b.w daily for 40 days. The n= 6 animals were dissected and the rest n=6 was administered orally with Curcuma longa rhizome ethanolic extract at the dose of 600mg/Kg b.w per day for 40 days. At the end of the entire experiment, all the animals were dissected out and their reproductive organs were taken out, especially epididymis for sperm counts, sperm motility, sperm mortality, sperm morphology. The blood samples were collected for the hormonal assay (testosterone and luteinizing hormone), as well as for hematological and biochemical analysis. The study showed a high magnitude of degeneration in the reproductive organs of the rats in the arsenic-treated group. There were degenerative fluctuations in the sperm counts, sperm motility, sperm mortality, sperm morphology and in the hormonal parameters, as well as in the hematological and biochemical parameters in the arsenic-treated rats. But, after the administration of Curcuma longa, there was significant amelioration in all these parameters. Therefore, the present study shows that Curcuma longa plays a vital role to combat arsenic-induced male reproductive toxicity.

Keywords: sodium arsenite, Charles foster rats, ethanolic rhizome extract of curcuma longa, male reproductive toxicity, amelioration

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Authors: Tong Ming Liu

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Human mesenchymal stem cells (MSCs) represent the most used stem cells for clinical application, which have been used in over 1000 clinical trials to treat over 30 diseases due to multilineage differentiation potential, secretome and immunosuppression. Gene therapies of MSCs hold great promise in the treatment of many diseases due to enhanced MSC-based clinical outcomes. To identify genes for gene therapy of MSCs, by comparing gene expression profile before and after MSC differentiation following by functional screening, we have identified ZNF145 that regulated MSC differentiation. Forced expression of ZNF145 resulted in enhanced in vitro chondrogenesis of MSCs as an upstream factor of SOX9 and improved osteochondral repair upon implant into osteochondral defects in rodents. By comparing gene expression profile during differentiation of iPSCs toward MSCs, we also identified gene HOX regulating MSC stemness, which was much downregulated in late-passaged MSCs. Knockdown of this gene greatly compromised MSC stemness including abolished proliferation, decreased CFU-F, promoted senescence and reduced expression of cell surface antigens linked to the MSC phenotype. In addition, multi-linage differentiation was also greatly impaired. Notably, HOX overexpression resulted in improved multi-lineage differentiation. In the mechanism, HOX expression significantly deceased in late passage of MSCs compared with early passage of MSCs, correlating with MSC important genes. ChIP-seq data shown that HOX binds to genes related to MSC self-renewal and differentiation. Most importantly, most HOX binding sites are lost in late passage of MSCs. HOX exerts its effects by directing binding Twist1, one important gene of MSCs. The identification of the genes regulating MSC differentiation and stemness will provide and promising strategies for gene therapy of MSCs in regenerative medicine.

Keywords: mesenchymal stem cell, novel transcription factor, stemness, gene therapy, cartilage repair, signaling pathway

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Authors: Meenu Joshi, Natalie Naidoo, Farzeen Kader

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Identification of body fluids is an essential step in forensic investigation to aid in crime reconstruction. Tissue-specific differentially methylated regions (tDMRs) of the human genome can be targeted to be used as biomarkers to differentiate between body fluids. The present study was undertaken to establish the methylation status of potential tDMRs in blood, semen, saliva, and vaginal fluid by using methylation-specific PCR (MSP) and bisulfite sequencing (BS). The methylation statuses of 3 potential tDMRS in genes ZNF282, PTPRS, and HPCAL1 were analysed in 10 samples of each body fluid. With MSP analysis, the ZNF282, and PTPRS1 tDMR displayed semen-specific hypomethylation while HPCAL1 tDMR showed saliva-specific hypomethylation. With quantitative analysis by BS, the ZNF282 tDMR showed statistically significant difference in overall methylation between semen and all other body fluids as well as at individual CpG sites (p < 0.05). To evaluate the effect of environmental conditions on the stability of methylation profiles of the ZNF282 tDMR, five samples of each body fluid were subjected to five different forensic simulated conditions (dry at room temperature, wet in an exsiccator, outside on the ground, sprayed with alcohol, and sprayed with bleach) for 50 days. Vaginal fluid showed highest DNA recovery under all conditions while semen had least DNA quantity. Under outside on the ground condition, all body fluids except semen showed a decrease in methylation level; however, a significant decrease in methylation level was observed for saliva. A statistical significant difference was observed for saliva and semen (p < 0.05) for outside on the ground condition. No differences in methylation level were observed for the ZNF282 tDMR under all conditions for vaginal fluid samples. Thus, in the present study ZNF282 tDMR has been identified as a novel and stable semen-specific hypomethylation marker.

Keywords: body fluids, bisulphite sequencing, forensics, tDMRs, MSP

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Authors: Som Pal Baliyan

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Dairy enterprise has been a major source of employment and income generation in most of the economies worldwide. Botswana government has also identified dairy as one of the agricultural sectors towards diversification of the mineral dependent economy of the country. The huge gap between local demand and supply of milk and milk products indicated that there are not only constraints but also; opportunities exist in this sub sector of agriculture. Therefore, this study was an attempt to identify constraints and opportunities in dairy production industry in Botswana. The possible ways to mitigate the constraints were also identified. The findings should assist the stakeholders especially, policy makers in the formulation of effective policies for the growth of dairy sector in the country. This quantitative study adopted a survey research design. A final survey followed by a pilot survey was conducted for data collection. The purpose of the pilot survey was to collect basic information on the nature and extent of the constraints, opportunities and ways to mitigate the constraints in dairy production. Based on the information from pilot survey, a four point Likert’s scale type questionnaire was constructed, validated and tested for its reliability. The data for the final survey were collected from purposively selected twenty five dairy farms. The descriptive statistical tools were employed to analyze data. Among the twelve constraints identified; high feed costs, feed shortage and availability, lack of technical support, lack of skilled manpower, high prevalence of pests and diseases and, lack of dairy related technologies were the six major constraints in dairy production. Grain feed production, roughage feed production, manufacturing of dairy feed, establishment of milk processing industry and, development of transportation systems were the five major opportunities among the eight opportunities identified. Increasing production of animal feed locally, increasing roughage feed production locally, provision of subsidy on animal feed, easy access to sufficient financial support, training of the farmers and, effective control of pests and diseases were identified as the six major ways to mitigate the constraints. It was recommended that the identified constraints and opportunities as well as the ways to mitigate the constraints need to be carefully considered by the stakeholders especially, policy makers during the formulation and implementation of the policies for the development of dairy sector in Botswana.

Keywords: dairy enterprise, milk production, opportunities, production constraints

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Authors: Nino G. Vepkhvadze, Tea Enukidze

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Every year the number of countries around the world face the risk of the spread of infectious diseases that bring significant ecological and social-economic damage. Hence, the importance of food product safety is emphasized that is the issue of interest for many countries. To solve them, it’s necessary to conduct preventive measures against the diseases, have accurate diagnostic results, leadership, and management. The Peste des petits ruminants (PPR) disease is caused by a morbillivirus closely related to the rinderpest virus. PPR is a transboundary disease as it emerges and evolves, considered as one of the top most damaging animal diseases. The disease imposed a serious threat to sheep-breeding when the farms of sheep, goats are significantly growing within the country. In January 2016, PPR was detected in Georgia. Up to present the origin of the virus, the age relationship of affected ruminants and the distribution of PPRV in Georgia remains unclear. Due to the nature of PPR, and breeding practices in the country, reemerging of the disease in Georgia is highly likely. The purpose of the studies is to provide laboratories with efficient tools allowing the early detection of PPR emergence and re-emergences. This study is being accomplished under the Biological Threat Reduction Program project with the support of the Defense Threat Reduction Agency (DTRA). The purpose of the studies is to investigate the samples and identify areas at high risk of the disease. Georgia has a high density of small ruminant herds bred as free-ranging, close to international borders. Kakheti region, Eastern Georgia, will be considered as area of high priority for PPR surveillance. For this reason, in 2019, in Kakheti region investigated n=484 sheep and goat serum and blood samples from the same animals, utilized serology and molecular biology methods. All samples were negative by RT-PCR, and n=6 sheep samples were seropositive by ELISA-Ab. Future efforts will be concentrated in areas where the risk of PPR might be high such as international bordering regions of Georgia. For diagnostics, it is important to integrate the PPRV knowledge with epidemiological data. Based on these diagnostics, the relevant agencies will be able to control the disease surveillance.

Keywords: animal disease, especially dangerous pathogen, laboratory diagnostics, virus

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Authors: L. Sun, T. Hargreaves, Z. Ahmad

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Newly-qualified Foundation Year 1 doctors in the United Kingdom are frequently expected to perform practical skills involving the upper limb in clinical practice (for example, venipuncture, cannulation, and blood gas sampling). However, a move towards systems-based undergraduate medical education in the United Kingdom often precludes or limits dedicated time to anatomy teaching with cadavers or prosections, favouring only applied anatomy in the context of pathology. The authors hypothesised that detailed anatomical knowledge may consequently be adversely affected, particularly with respect to long-term retention. A simple picture quiz and accompanying questionnaire testing the identification of 7 upper limb surface landmarks was distributed to a total of 98 final year medical students from two universities - one with a systems-based curriculum, and one with a dedicated longitudinal dissection-based anatomy module in the first year of study. Students with access to dissection and prosection-based anatomy teaching performed more strongly, with a significantly higher rate of correct identification of all but one of the landmarks. Furthermore, it was notable that none of the students who had previously undertaken a systems-based course scored full marks, compared with 20% of those who had participated in the more dedicated anatomy course. This data suggests that a traditional, dissection-based approach to undergraduate anatomy teaching is superior to modern system-based curricula, in terms of aiding long-term retention of anatomical knowledge pertinent to newly-qualified doctors. The authors express concern that this deficit in proficiency could be detrimental to patient care in clinical practice, and propose that, where dissection-led anatomy teaching is not available, further anatomy revision modules are implemented throughout undergraduate education to aid knowledge retention and support clinical excellence.

Keywords: dissection, education, surface anatomy, upper limb

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Authors: M. Sakthivel, A. Devaki, D. Balasubramanyam, P. Kumarasamy, A. Raja, R. Anilkumar, H. Gopi

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The genetic parameters of growth traits in the New Zealand White rabbits maintained at Sheep Breeding and Research Station, Sandynallah, The Nilgiris, India were estimated by partitioning the variance and covariance components. The (co)variance components of body weights at weaning (W42), post-weaning (W70) and marketing (W135) age and growth efficiency traits viz., average daily gain (ADG), relative growth rate (RGR) and Kleiber ratio (KR) estimated on a daily basis at different age intervals (1=42 to 70 days; 2=70 to 135 days and 3=42 to 135 days) from weaning to marketing were estimated by restricted maximum likelihood, fitting six animal models with various combinations of direct and maternal effects. Data were collected over a period of 15 years (1998 to 2012). A log-likelihood ratio test was used to select the most appropriate univariate model for each trait, which was subsequently used in bivariate analysis. Heritability estimates for W42, W70 and W135 were 0.42 ± 0.07, 0.40 ± 0.08 and 0.27 ± 0.07, respectively. Heritability estimates of growth efficiency traits were moderate to high (0.18 to 0.42). Of the total phenotypic variation, maternal genetic effect contributed 14 to 32% for early body weight traits (W42 and W70) and ADG1. The contribution of maternal permanent environmental effect varied from 6 to 18% for W42 and for all the growth efficiency traits except for KR2. Maternal permanent environmental effect on most of the growth efficiency traits was a carryover effect of maternal care during weaning. Direct maternal genetic correlations, for the traits in which maternal genetic effect was significant, were moderate to high in magnitude and negative in direction. Maternal effect declined as the age of the animal increased. The estimates of total heritability and maternal across year repeatability for growth traits were moderate and an optimum rate of genetic progress seems possible in the herd by mass selection. The estimates of genetic and phenotypic correlations among body weight traits were moderate to high and positive; among growth efficiency traits were low to high with varying directions; between body weights and growth efficiency traits were very low to high in magnitude and mostly negative in direction. Moderate to high heritability and higher genetic correlation in body weight traits promise good scope for genetic improvement provided measures are taken to keep the inbreeding at the lowest level.

Keywords: genetic parameters, growth traits, maternal effects, rabbit genetics

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Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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Authors: Berina Pilipović, Saša Pilipović, Maja Pašić-Kulenović

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Inflammation is the body's response to impaired homeostasis caused by infection, injury or trauma resulting in systemic and local effects. Inflammation causes the body's response to injury and is characterized by a series of events including inflammatory response, response to pain receptors and the recovery process. Inflammation can be acute and chronic. The inflammatory response is described in three different phases. Free radical is an atom or molecule that has the unpaired electron and is therefore generally very reactive chemical species. Biologically important example of reaction with free radicals is called Lipid peroxidation (LP). Lipid peroxidation reactions occur in biological membranes, and if at the outset is not stopped with the action of antioxidants, it will bring damage to the membrane, which results in partial or complete loss of their physiological functions. Calcium antagonists and beta-adrenergic receptor antagonists are known drugs, and for many years and widely used in the treatment of cardiovascular diseases. Some of these compounds also show antioxidant activity. The mechanism of antioxidant activities of calcium antagonists and beta-blockers is unknown, since their structure varies widely. This research investigated the possible local anti-inflammatory activity of ointments containing 1% carvedilol in the white petrolatum USP. Ear inflammation was induced by 3% croton oil acetone solution, in quantity of 10 µl on both mouse ears. Albino Swiss mouse (n = 8) are treated with 2.5 mg/ear ointment, and control group was treated on the same way as previous with hydrocortisone 1% ointment (2.5 mg/ear). The other ear of the same animal was used as control one. Ointments were administered once per day, on the left ear. After treatment, ears were observed for three days. After three days, we measured mass (mg) of 6 mm ear punch of treated and controlled ears. The results of testing anti-inflammatory effects of ointments with carvedilol in the mouse ear model show stronger observed effect than ointment with 1% hydrocortisone in the same basis. Identical results were confirmed by the difference between the mass of 6 mm ears punch. The results were also confirmed by histological examination. Ointments with carvedilol showed significant reduction of the inflammation process caused by croton oil on the mouse inflammation model.

Keywords: antioxidant, carvedilol, inflammation, mouse ear

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