Search results for: reality therapy

Authors: Lakmali Anthony, Madeline Gillies

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Background: Colorectal cancer (CRC) is usually managed with surgical resection. Many of the outcomes traditionally used to define successful operative management, such as resection margin, do not adequately reflect patients’ experience. Patient-reported outcomes (PRO), such as Health-Related Quality of life (HRQoL), provide a means by which the impact of surgery for cancer can be reported in a patient-centered way. HRQoL has previously been shown to be impacted by psychosocial, behavioral and disease-specific characteristics. This exploratory cross-sectional study aims to; (1) describe postoperative HRQoL in patients who underwent primary resection in a regional Australian hospital; (2) describe the prevalence of anxiety, depression and clinically significant fear of cancer recurrence (FCR) in this population; and (3) identify demographic, psychosocial, disease and treatment factors associated with poorer self-reported HRQoL. Methods: Consecutive patients who had resection of colorectal cancer in a single regional Australian hospital between 2015 and 2022 were eligible. Participants were asked to complete a survey instrument designed to assess HRQoL, as well as validated instruments that assess several other psychosocial PROs hypothesized to be associated with HRQoL; emotional distress, fear of cancer recurrence, social support, dispositional optimism, body image and spirituality. Demographic and disease-specific data were also collected via medical record review. Results: Forty-six patients completed the survey. Clinically significant levels of fear of recurrence as well as emotional distress, were present in this group. Many domains of HRQoL were significantly worse than an Australian reference population for CRC. Demographic and disease factors associated with poor HRQoL included smoking and ongoing adjuvant systemic therapy. The primary operation was not associated with HRQoL; however, the operative approach (laparoscopic vs. open) was associated with HRQoL for these patients. All psychosocial factors measured were associated with HRQoL, including cancer worry, emotional distress, body image and dispositional optimism. Conclusion: HRQoL is an important outcome in surgery for both research and clinical practice. This study provides an overview of the quality of life in a regional Australian population of postoperative colorectal cancer patients and the factors that affect it. Understanding HRQoL and awareness of patients particularly vulnerable to poor outcomes should be used to aid the informed consent and shared decision-making process between surgeon and patient.

Keywords: surgery, colorectal, cancer, PRO, HRQoL

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Authors: S. Delgado, C. Cerrada, R. S. Gómez

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This research introduces an approach to voxelizing the surfaces of triangular meshes with efficiency and accuracy. Our method leverages parallel equidistant scan-lines and introduces a Gap Detection technique to address the limitations of existing approaches. We present a comprehensive study showcasing the method's effectiveness, scalability, and versatility in different scenarios. Voxelization is a fundamental process in computer graphics and simulations, playing a pivotal role in applications ranging from scientific visualization to virtual reality. Our algorithm focuses on enhancing the voxelization process, especially for complex models and high resolutions. One of the major challenges in voxelization in the Graphics Processing Unit (GPU) is the high cost of discovering the same voxels multiple times. These repeated voxels incur in costly memory operations with no useful information. Our scan-line-based method ensures that each voxel is detected exactly once when processing the triangle, enhancing performance without compromising the quality of the voxelization. The heart of our approach lies in the use of parallel, equidistant scan-lines to traverse the interiors of triangles. This minimizes redundant memory operations and avoids revisiting the same voxels, resulting in a significant performance boost. Moreover, our method's computational efficiency is complemented by its simplicity and portability. Written as a single compute shader in Graphics Library Shader Language (GLSL), it is highly adaptable to various rendering pipelines and hardware configurations. To validate our method, we conducted extensive experiments on a diverse set of models from the Stanford repository. Our results demonstrate not only the algorithm's efficiency, but also its ability to produce 26 tunnel free accurate voxelizations. The Gap Detection technique successfully identifies and addresses gaps, ensuring consistent and visually pleasing voxelized surfaces. Furthermore, we introduce the Slope Consistency Value metric, quantifying the alignment of each triangle with its primary axis. This metric provides insights into the impact of triangle orientation on scan-line based voxelization methods. It also aids in understanding how the Gap Detection technique effectively improves results by targeting specific areas where simple scan-line-based methods might fail. Our research contributes to the field of voxelization by offering a robust and efficient approach that overcomes the limitations of existing methods. The Gap Detection technique fills a critical gap in the voxelization process. By addressing these gaps, our algorithm enhances the visual quality and accuracy of voxelized models, making it valuable for a wide range of applications. In conclusion, "Closing the Gap: Efficient Voxelization with Equidistant Scan-lines and Gap Detection" presents an effective solution to the challenges of voxelization. Our research combines computational efficiency, accuracy, and innovative techniques to elevate the quality of voxelized surfaces. With its adaptable nature and valuable innovations, this technique could have a positive influence on computer graphics and visualization.

Keywords: voxelization, GPU acceleration, computer graphics, compute shaders

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Authors: Selin Guney, Andres Riquelme

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Among the main purposes of optimal and efficient forecasts of agricultural commodity prices is to guide the firms to advance the economic decision making process such as planning business operations and marketing decisions. Governments are also the beneficiaries and suppliers of agricultural price forecasts. They use this information to establish a proper agricultural policy, and hence, the forecasts affect social welfare and systematic errors in forecasts could lead to a misallocation of scarce resources. Various empirical approaches have been applied to forecast commodity prices that have used different methodologies. Most commonly-used approaches to forecast commodity sectors depend on classical time series models that assume values of the response variables are precise which is quite often not true in reality. Recently, this literature has mostly evolved to a consideration of fuzzy time series models that provide more flexibility in terms of the classical time series models assumptions such as stationarity, and large sample size requirement. Besides, fuzzy modeling approach allows decision making with estimated values under incomplete information or uncertainty. A number of fuzzy time series models have been developed and implemented over the last decades; however, most of them are not appropriate for forecasting repeated and nonconsecutive transitions in the data. The modeling scheme used in this paper eliminates this problem by introducing Markov modeling approach that takes into account both the repeated and nonconsecutive transitions. Also, the determination of length of interval is crucial in terms of the accuracy of forecasts. The problem of determining the length of interval arbitrarily is overcome and a methodology to determine the proper length of interval based on the distribution or mean of the first differences of series to improve forecast accuracy is proposed. The specific purpose of this paper is to propose and investigate the potential of a new forecasting model that integrates methodologies for determining the proper length of interval based on the distribution or mean of the first differences of series and Fuzzy Time Series- Markov Chain model. Moreover, the accuracy of the forecasting performance of proposed integrated model is compared to different univariate time series models and the superiority of proposed method over competing methods in respect of modelling and forecasting on the basis of forecast evaluation criteria is demonstrated. The application is to daily corn and soybean prices observed at three commercially important North Carolina markets; Candor, Cofield and Roaring River for corn and Fayetteville, Cofield and Greenville City for soybeans respectively. One main conclusion from this paper is that using fuzzy logic improves the forecast performance and accuracy; the effectiveness and potential benefits of the proposed model is confirmed with small selection criteria value such MAPE. The paper concludes with a discussion of the implications of integrating fuzzy logic and nonarbitrary determination of length of interval for the reliability and accuracy of price forecasts. The empirical results represent a significant contribution to our understanding of the applicability of fuzzy modeling in commodity price forecasts.

Keywords: commodity, forecast, fuzzy, Markov

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Authors: Su Yin Chiam, Zhipeng Ding, Guang Yang, Danny Jian Hang Tng, Peiyi Song, Geok Ing Ng, Ken-Tye Yong, Qing Xin Zhang

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Brain-machine interfaces (BMI) is a ground rich of exploration opportunities where manipulation of neural activity are used for interconnect with myriad form of external devices. These research and intensive development were evolved into various areas from medical field, gaming and entertainment industry till safety and security field. The technology were extended for neurological disorders therapy such as obsessive compulsive disorder and Parkinson’s disease by introducing current pulses to specific region of the brain. Nonetheless, the work to develop a real-time observing, recording and altering of neural signal brain-machine interfaces system will require a significant amount of effort to overcome the obstacles in improving this system without delay in response. To date, feature size of interface devices and the density of the electrode population remain as a limitation in achieving seamless performance on BMI. Currently, the size of the BMI devices is ranging from 10 to 100 microns in terms of electrodes’ diameters. Henceforth, to accommodate the single cell level precise monitoring, smaller and denser Nano-scaled nanowire electrode arrays are vital in fabrication. In this paper, we would like to showcase the fabrication of high aspect ratio of vertical silicon nanowire electrodes arrays using microelectromechanical system (MEMS) method. Nanofabrication of the nanowire electrodes involves in deep reactive ion etching, thermal oxide thinning, electron-beam lithography patterning, sputtering of metal targets and bottom anti-reflection coating (BARC) etch. Metallization on the nanowire electrode tip is a prominent process to optimize the nanowire electrical conductivity and this step remains a challenge during fabrication. Metal electrodes were lithographically defined and yet these metal contacts outline a size scale that is larger than nanometer-scale building blocks hence further limiting potential advantages. Therefore, we present an integrated contact solution that overcomes this size constraint through self-aligned Nickel silicidation process on the tip of vertical silicon nanowire electrodes. A 4 x 4 array of vertical silicon nanowires electrodes with the diameter of 290nm and height of 3µm has been successfully fabricated.

Keywords: brain-machine interfaces, microelectromechanical systems (MEMS), nanowire, nickel silicide

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Authors: Leila Fozouni, Anahita Mazandarani

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Background: Maternal infections are the most common cause of infections in infants, and the level of infection and its severity highly depends on the degree of colonization of the bacteria in the mother; so, the occurrence of aggressive diseases is not unpredictable in mothers with very high colonization. Group B Streptococcus is part of the normal flora of the gastrointestinal and genital tracts in women and is the leading cause of septicemia and meningitis in newborns. Today Zinc oxide nanoparticle is regarded as one of the most commonly used and safest nanoparticles for defeating Gram-positive and Gram-negative bacteria. This study aims to determine the antibacterial effects of Zinc oxide on the growth of drug-resistant group B Streptococcus strains isolated from pregnant women. Materials and Methods: This cross-sectional study was conducted on 150 pregnant women of 28–37 weeks admitted to seven hospitals and maternity wards in Golestan province, northeast of Iran. For bacterial identification, rectovaginal swabs were firstly inoculated to the Todd-Hewitt Broth and cultured in blood agar (containing 5% sheep blood). Then microbiologic and PCR methods were performed to detect group B Streptococci. Disk diffusion and broth microdilution tests were used to determine the bacterial susceptibility to antibiotics according to CLSI M100(2021) criteria. The antibacterial properties of Zinc oxide nanoparticles were evaluated using the agar well-diffusion method. Results: The prevalence of group B Streptococcus was 18% in pregnant women. Out of twenty-seven positive cultures, 62.96% were higher than thirty years old. Ninety percent and 45% of isolates were resistant to clindamycin and erythromycin, respectively, and susceptibility to cefazolin was 71%. In addition, susceptibility to ampicillin and penicillin were 74% and 55%, respectively. The results showed that 82% of erythromycin-resistant, 92% clindamycin-resistant, and 78% of cefazolin-resistant isolates were eliminated by zinc oxide nanoparticles at a concentration of 100 mg/L of the nanoparticle. Furthermore, ZnONPs could inhibit all drug-resistant isolates at a concentration of 200 mg/mL (MIC90 ≥ 200). Conclusion: Since the drug resistance of group B streptococci against various antibiotics is increasing, determining and investigating the drug-resistance pattern of this bacterium to different antibiotics in order to prevent arbitrary consumption of antibiotics by pregnant women and ultimately prevent Infant mortality seems necessary. Generally, ZnONPs showed a high antimicrobial effect, and it was revealed that the bactericide effect increases upon the increase in the concentration of the nanoparticle.

Keywords: group B beta-hemolytic streptococcus, pregnant women, zinc oxide nanoparticles, drug resistance

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Authors: Miria Gambardella

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The influence of solidarity demonstrations towards the Zapatista National Liberation Army has been constantly present over the years, both locally and internationally, guaranteeing visibility to the cause, shaping the movement’s choices, and influencing its hopes of impact worldwide. Most of the coffee produced by the autonomous cooperatives from Chiapas is exported, therefore making coffee trade the main income from international solidarity networks. The question arises about the implications of the relations established between the communities in resistance in Southeastern Mexico and international solidarity movements, specifically on the strategies adopted to conciliate army's demands for autonomy and economic asymmetries between Zapatista cooperatives producing coffee and European collectives who hold purchasing power. In order to deepen the inquiry on those topics, a year-long multi-site investigation was carried out. The first six months of fieldwork were based in Barcelona, where Zapatista coffee was first traded in Spain and where one of the historical and most important European solidarity groups can be found. The last six months of fieldwork were carried out directly in Chiapas, in contact with coffee producers, Zapatista political authorities, international activists as well as vendors, and the rest of the network implicated in coffee production, roasting, and sale. The investigation was based on qualitative research methods, including participatory observation, focus groups, and semi-structured interviews. The analysis did not only focus on retracing the steps of the market chain as if it could be considered a linear and unilateral process, but it rather aimed at exploring actors’ reciprocal perceptions, roles, and dynamics of power. Demonstrations of solidarity and the money circulation they imply aim at changing the system in place and building alternatives, among other things, on the economic level. This work analyzes the formulation of discourse and the organization of solidarity activities that aim at building opportunities for action within a highly politicized economic sphere to which access must be regularly legitimized. The meaning conveyed by coffee is constructed on a symbolic level by the attribution of moral criteria to transactions. The latter participate in the construction of imaginaries that circulate through solidarity movements with the Zapatista rebellion. Commercial exchanges linked to solidarity networks turned out to represent much more than monetary transactions. The social, cultural, and political spheres are invested by ethics, which penetrates all aspects of militant action. It is at this level that the boundaries of different collective actors connect, contaminating each other: merely following the money flow would have been limiting in order to account for a reality within which imaginary is one of the main currencies. The notions of “trust”, “dignity” and “reciprocity” are repeatedly mobilized to negotiate discontinuous and multidirectional flows in the attempt to balance and justify commercial relations in a politicized context that characterizes its own identity through demonizing “market economy” and its dehumanizing powers.

Keywords: coffee trade, economic anthropology, international cooperation, Zapatista National Liberation Army

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Authors: E. Nemes-Nagy, E. Fogarasi, M. Croitoru, A. Nyárádi, K. Komlódi, S. Pál, A. Kovács, O. Kopácsy, R. Tripon, Z. Fazakas, C. Uzun, Z. Simon-Szabó, V. Balogh-Sămărghițan, E. Ernő Nagy, M. Szabó, M. Tilinca

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Intense oxidative stress, increased glycated hemoglobin and mineral imbalance represent risk factors for complications in diabetic patients. Cardiovascular complications are most common in these patients, including nephropathy. This study was conducted in 2015 at the Procardia Laboratory in Tîrgu Mureș, Romania on 40 type 2 diabetic adults. Routine biochemical tests were performed on the Konleab 20XTi analyzer (serum glucose, total cholesterol, LDL and HDL cholesterol, triglyceride, creatinine, urea). We also measured serum uric acid, magnesium and calcium concentration by photometric procedures, potassium, sodium and chloride by ion selective electrode, and chromium by atomic absorption spectrometry in a group of patients. Glycated hemoglobin (HbA1c) dosage was made by reflectometry. Urine analysis was performed using the HandUReader equipment. The level of oxidative stress was measured by serum malondialdehyde dosage using the thiobarbituric acid reactive substances method. MDRD (Modification of Diet in Renal Disease) formula was applied for calculation of creatinine-derived glomerular filtration rate. GraphPad InStat software was used for statistical analysis of the data. The diabetic subject included in the study presented high MDA concentrations, showing intense oxidative stress. Calcium was deficient in 5% of the patients, chromium deficiency was present in 28%. The atherogenic cholesterol fraction was elevated in 13% of the patients. Positive correlation was found between creatinine and MDRD-creatinine values (p<0.0001), 68% of the patients presented increased creatinine values. The majority of the diabetic patients had good control of their diabetes, having optimal HbA1c values, 35% of them presented fasting serum glucose over 120 mg/dl and 18% had glucosuria. Intense oxidative stress and mineral deficiencies can increase the risk of cardiovascular complications in diabetic patients in spite of their good metabolic balance. More than two third of the patients present biochemical signs of nephropathy, cystatin C dosage and microalbuminuria could reveal better the kidney disorder, but glomerular filtration rate calculation formulas are also useful for evaluation of renal function.

Keywords: cardiovascular risk, homocysteine, malondialdehyde, metformin, minerals, type 2 diabetes, vitamin B12

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Authors: Bu Kyung Park

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Background: The survival rate of pediatric cancer patients has been increased. Thus, the needs of long-term management and follow-up education after discharge continue to grow. Purpose: The purpose of this study was to explore the experiences of pediatric cancer patients and their families from first diagnosis to returning their social life. The ultimate goal of this study was to assess which information and intervention did pediatric cancer patients and their families required and needed, so that this could provide fundamental information for developing educational content of web-based intervention program for pediatric cancer patients. Research Approach: This study was based on a descriptive qualitative research design using semi-structured focus group interview. Participants: Twelve pediatric cancer patients and 12 family members participated in a total six focus group interview sessions. Methods: All interviews were audiotaped after obtaining participants’ approval. The recordings were transcribed. Qualitative Content analysis using the inductive coding approach was performed on the transcriptions by three coders. Findings: Eighteen categories emerged from the six main themes: 1) Information needs, 2) Support system, 3) Barriers to treatment, 4) Facilitators to treatment, 5) Return to social life, 6) Healthcare system issues. Each theme had both pediatric cancer patients’ codes and their family members’ codes. Patients and family members had high information needs through the whole process of treatment, not only the first diagnosis but also after completion of treatment. Hospitals provided basic information on chemo therapy, medication, and various examinations. However, they were more likely to rely on information from other patients and families by word of mouth. Participants’ information needs were different according to their treatment stage (e.g., first admitted patients versus cancer survivors returning to their social life). Even newly diagnosed patients worried about social adjustment after completion of all treatment, such as return to school and diet and physical activity at home. Most family members had unpleasant experiences while they were admitted in hospitals and concerned about healthcare system issues, such as medical error and patient safety. Conclusions: In conclusion, pediatric cancer patients and their family members wanted information source which can provide tailored information based on their needs. Different information needs with patients and their family members based on their diagnosis, progress, stage of treatment were identified. Findings from this study will be used to develop a patient-centered online health intervention program for pediatric cancer patients. Pediatric cancer patients and their family members had variety fields of education needs and soak the information from various sources. Web-based health intervention program for them is required to satisfy their inquiries to provide reliable information.

Keywords: focus group interview, family caregivers, pediatric cancer patients, qualitative content analysis

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Authors: Itee Chowdhury, Shikha Modi

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Introduction: Cancer is beginning to outpace cardiovascular disease as a cause of death affecting every major organ system with profound implications for perioperative management. Breast cancer is the most common cancer in women in India, accounting for 27% of all cancers. The small changes in analgesic management of cancer patients can greatly improve prognosis and reduce the risk of postsurgical cancer recurrence as opioid-based analgesia has a deleterious effect on cancer outcomes. Shortened postsurgical recovery time facilitates earlier return to intended oncological therapy maximising the chance of successful treatment. Literature reveals that the role of BIS since FDA approval has been assessed in various types of surgeries, but clinical data on its use in oncosurgical patients are scanty. Our study focuses on the role of BIS-guided anaesthesia for breast cancer surgery patients. Methods: A prospective randomized controlled study in patients aged 36-55years scheduled for modified radical mastectomy was conducted in 51 patients in each group who met the inclusion and exclusion criteria, and randomization was done by sealed envelope technique. In BIS guided anaesthesia group (B), sevoflurane was titrated to keep the BIS value 45-60, and thereafter if the patient showed hypertension/tachycardia, an opioid was given. In standard anaesthesia care (group C), sevoflurane was titrated to keep MAC in the range of 0.8-1, and fentanyl was given if the patient showed hypertension/tachycardia. Intraoperative opioid consumption was calculated. Postsurgery recovery characteristics, including Aldrete score, were assessed. Patients were questioned for pain, PONV, and recall of the intraoperative event. A comparison of age, BMI, ASA, recovery characteristics, opioid, and VAS score was made using the non-parametric Mann-Whitney U test. Categorical data like intraoperative awareness of surgery and PONV was studied using the Chi-square test. A comparison of heart rate and MAP was made by an independent sample t-test. #ggplot2 package was used to show the trend of the BIS index for all intraoperative time points for each patient. For a statistical test of significance, the cut-off p-value was set as <0.05. Conclusions: BIS monitoring led to reduced opioid consumption and early recovery from anaesthesia in breast cancer patients undergoing MRM resulting in less postoperative nausea and vomiting and less pain intensity in the immediate postoperative period without any recall of the intraoperative event. Thus, the use of a Bispectral index monitor allows for tailoring of anaesthesia administration with a good outcome.

Keywords: bispectral index, depth of anaesthesia, recovery, opioid consumption

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Authors: Maria Lucia G. Lourenco, Keylla H. N. P. Pereira, Vivane Y. Hibaru, Fabiana F. Souza, Joao C. P. Ferreira, Simone B. Chiacchio, Luiz H. A. Machado

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Neonatal sepsis is a systemic response to the acute generalized infection caused by one or more bacterial agents, representing the main infectious cause of neonatal mortality in dogs during the first three weeks of life. This study aims to describe the incidence of sepsis in neonate dogs, as well as the main clinical signs and mortality rates. The study included 735 neonates admitted to the Sao Paulo State University (UNESP) Veterinary Hospital, Botucatu, Sao Paulo, Brazil, between January 2018 and November 2019. Seven hundred thirty-five neonates, 14% (98/703) presented neonatal sepsis. The main sources of infection for the neonates were intrauterine (72.5%, 71/98), lactogenic (13.2%, 13/98), umbilical (5.1%, 5/98) and unidentified sources (9.2%, 9/98). The main non-specific clinical signs observed in the newborns were weakness, depression, impaired or absent reflexes, hypothermia, hypoglycemia, dehydration, reduced muscle tonus and diarrhea. The newborns also manifested clinical signs of severe infection, such as hyperemia in the abdominal and anal regions, omphalitis, hematuria, abdomen and extremities with purplish-blue coloration necrosing injuries in the pads, bradycardia, dyspnea, epistaxis, hypotension and evolution to septic shock. Infections acquired during intrauterine life led to the onset of the clinical signs at the time of birth, with fast evolution during the first hours of life. On the other hand, infections acquired via milk or umbilical cord presented clinical signs later. The total mortality rate was 5.4% (38/703) and the mortality rate among the neonates with sepsis was 38.7% (38/98). The early mortality rate (0 to 2 days) accounted for 86.9% (33/38) and the late mortality rate (3 to 30 days) for 13.1% (5/38) of the deaths among the newborns with sepsis. The main bacterial agents observed were Staphylococcus spp., Streptococcus spp., Proteus spp. Mannheimia spp. and Escherichia coli. Neonatal sepsis evolves quickly and may lead to high mortality in a litter. The prognosis is usually favorable if the diagnosis is reached early and the antibiotic therapy instituted as soon as possible, even before the results of blood cultures and antibiograms. The therapeutic recommendations should meet the special physiological conditions of a neonate in terms of metabolism and excretion of medication. Therefore, it is of utmost importance that the veterinarian is knowledgeable regarding neonatology to provide effective intervention and improve the survival rates of these patients.

Keywords: Neonatal infection , bacteria, puppies, newborn

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Authors: Sudhir Kumar, V. R. Sinha

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Background: The topical and systemic toxicity associated with present nonmelanoma skin cancer (NMSC) treatment therapy using 5-Fluorouracil (5-FU) make it necessary to develop a novel delivery system having lesser toxicity and better control over drug release. Solid lipid nanoparticles offer many advantages like: controlled and localized release of entrapped actives, nontoxicity, and better tolerance. Aim:-To investigate safety and efficacy of 5-FU loaded solid lipid nanoparticles as a topical delivery system for the treatment of nonmelanoma skin cancer. Method: Topical solid lipid nanoparticles of 5-FU were prepared using Compritol 888 ATO (Glyceryl behenate) as lipid component and pluronic F68 (Poloxamer 188), Tween 80 (Polysorbate 80), Tyloxapol (4-(1,1,3,3-Tetramethylbutyl) phenol polymer with formaldehyde and oxirane) as surfactants. The SLNs were prepared with emulsification method. Different formulation parameters viz. type and ratio of surfactant, ratio of lipid and ratio of surfactant:lipid were investigated on particle size and drug entrapment efficiency. Results: Characterization of SLNs like–Transmission Electron Microscopy (TEM), Differential Scannig calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Particle size determination, Polydispersity index, Entrapment efficiency, Drug loading, ex vivo skin permeation and skin retention studies, skin irritation and histopathology studies were performed. TEM results showed that shape of SLNs was spherical with size range 200-500nm. Higher encapsulation efficiency was obtained for batches having higher concentration of surfactant and lipid. It was found maximum 64.3% for SLN-6 batch with size of 400.1±9.22 nm and PDI 0.221±0.031. Optimized SLN batches and marketed 5-FU cream were compared for flux across rat skin and skin drug retention. The lesser flux and higher skin retention was obtained for SLN formulation in comparison to topical 5-FU cream, which ensures less systemic toxicity and better control of drug release across skin. Chronic skin irritation studies lacks serious erythema or inflammation and histopathology studies showed no significant change in physiology of epidermal layers of rat skin. So, these studies suggest that the optimized SLN formulation is efficient then marketed cream and safer for long term NMSC treatment regimens. Conclusion: Topical and systemic toxicity associated with long-term use of 5-FU, in the treatment of NMSC, can be minimized with its controlled release with significant drug retention with minimal flux across skin. The study may provide a better alternate for effective NMSC treatment.

Keywords: 5-FU, topical formulation, solid lipid nanoparticles, non melanoma skin cancer

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Authors: Shivayogi Charantimath

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Radiotherapy and chemotherapy are effective for treating malignancies but are associated with side effects like oral mucositis. Chlorhexidine gluconate is one of the most commonly used mouthwash in prevention of signs and symptoms of mucositis. Evidence shows that chlorhexidine gluconate has side effects in terms of colonization of bacteria, bad breadth and less healing properties. Thus, it is essential to find a suitable alternative therapy which is more effective with minimal side effects. Curcumin, an extract of turmeric is gradually being studied for its wide-ranging therapeutic properties such as antioxidant, analgesic, anti-inflammatory, antitumor, antimicrobial, antiseptic, chemo sensitizing and radio sensitizing properties. The present study was conducted to evaluate the efficacy and safety of topical curcumin gel on radio-chemotherapy induced oral mucositis in cancer patients. The aim of the study is to evaluate the efficacy and safety of curcumin gel in the management of oral mucositis in cancer patients undergoing radio chemotherapy and compare with chlorhexidine. The study was conducted in K.L.E. Society’s Belgaum cancer hospital. 40 oral cancer patients undergoing the radiochemotheraphy with oral mucositis was selected and randomly divided into two groups of 20 each. The study group A [20 patients] was advised Cure next gel for 2 weeks. The control group B [20 patients] was advised chlorhexidine gel for 2 weeks. The NRS, Oral Mucositis Assessment scale and WHO mucositis scale were used to determine the grading. The results obtained were calculated by using SPSS 20 software. The comparison of grading was done by applying Mann-Whitney U test and intergroup comparison was calculated by Wilcoxon matched pairs test. The NRS scores observed from baseline to 1^st and 2^nd week follow up in both the group showed significant difference. The percentage of change in erythema in respect to group A was 63.3% for first week and for second week, changes were 100.0% with p = 0.0003. The changes in Group A in respect to erythema was 34.6% for 1^st week and 57.7% in second week. The intergroup comparison was significant with p value of 0.0048 and 0.0006 in relation to group A and group B respectively. The size of the ulcer score was measured which showed 35.5% [P=0.0010] of change in Group A for 1^st and 2^nd week showed totally reduction i.e. 103.4% [P=0.0001]. Group B showed 24.7% change from baseline to 1^st week and 53.6% for 2^nd week follow up. The intergroup comparison with Wilcoxon matched pair test was significant with p=0.0001 in group A. The result obtained by WHO mucositis score in respect to group A shows 29.6% [p=0.0004] change in first week and 75.0% [p=0.0180] change in second week which is highly significant in comparison to group B. Group B showed minimum changes i.e. 20.1% in 1^st week and 33.3% in 2^nd week. The p value with Wilcoxon was significant with 0.0025 in Group A for 1^st week follow up and 0.000 for 2^nd week follow up. Curcumin gel appears to an effective and safer alternative to chlorhexidine gel in treatment of oral mucositis.

Keywords: curcumin, chemotheraphy, mucositis, radiotheraphy

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Authors: Geovana Soncin, Larissa Berti

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Some aspects of prosody acquisition remain still unclear, especially regarding atypical speech development processes. This work deals with prosody acquisition and its implications for clinical purposes. Therefore, we analyze speech samples produced by adult speakers, children in typical language development, and children with phonological disorders. Phonological disorder comprises deviating manifestations characterized by inconsistencies in the phonological representation of a linguistic system under acquisition. The clinical assessment is performed mostly based on contrasts whose manifestations occur in the segmental level of a phonological system. Prosodic organization of spoken utterances is not included in the standard assessment. However, assuming that prosody is part of the phonological system, it was hypothesized that children with Phonological Disorders could present inconsistencies that also occur at a prosodic level. Based on this hypothesis, the paper aims to analyze contrastive focus marking in the speech of children with Phonological Disorders in comparison with the speech of children under Typical Language Development and adults. The participants of all groups were native speakers of Brazilian Portuguese. The investigation was designed in such a way as to identify differences and similarities among the groups that could be interpreted as clues of normal or deviant processes of prosody acquisition. Contrastive focus in Brazilian Portuguese is marked by increasing duration, f0, and intensity on the focused element as well as by a particular type of pitch accent (L*+H). Thirty-nine subjects participated, thirteen from each group. Acoustic analysis was performed, considering duration, intensity, and intonation as parameters. Children with PD were recruited in sessions from a service provided by Speech-Language Pathology Therapy; children in TD, paired in age and sex with the first group, were recruited in a regular school; and 20-24 years old adults were recruited from a University class. In a game prepared to elicit focused sentences, all of them produced the sentence “Girls love red dress,” marking focus on different syntactic positions: subject, verb, and object. Results showed that adults, children in typical language development, and children with Phonological Disorders marked contrastive focus differently: typical children used all parameters like adults do; however, in comparison with them, they exaggerated duration and, in the opposite direction, they did not increase f0 in a sufficient magnitude as adults; children with Phonological Disorder presented inconsistencies in duration, not increasing it in some syntactic positions, and also in intonation, not producing the representative pitch accent of contrastive focus. The results suggest prosody is also affected by phonological disorder and give clues of developmental processes of prosody acquisition.

Keywords: Brazilian Portuguese, contrastive focus, phonological disorder, prosody acquisition

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Authors: Gustavo Axel Elizalde-Velázquez

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Metformin is the first line of oral therapy to treat type II diabetes and is also employed as a treatment for other indications, such as polycystic ovary syndrome, cancer, and COVID-19. Recent data suggest it is the aspirin of the 21st century due to its antioxidant and anti-aging effects. However, increasingly current articles indicate its long-term consumption generates mitochondrial impairment. Up to date, it is known metformin increases the biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription, but further information related to brain damage after its consumption is missing. Bearing in mind the above, this work aimed to establish whether or not chronic exposure to metformin may alter swimming behavior and induce neurotoxicity in Danio rerio adults. For this purpose, 250 Danio rerio grown-ups were assigned to six tanks of 50 L of capacity. Four of the six systems contained 50 fish, while the remaining two had 25 fish (≈1 male:1 female ratio). Every system with 50 fish was allocated one of the three metformin treatment concentrations (1, 20, and 40 μg/L), with one system as the control treatment. Systems with 25 fish, on the other hand, were used as positive controls for acetylcholinesterase (10 μg/L of Atrazine) and oxidative stress (3 μg/L of Atrazine). After four months of exposure, a mean of 32 fish (S.D. ± 2) per group of MET treatment survived, which were used for the evaluation of behavior with the Novel Tank test. Moreover, after the behavioral assessment, we aimed to collect the blood and brains of all fish from all treatment groups. For blood collection, fish were anesthetized with an MS-222 solution (150 mg/L), while for brain gathering, fish were euthanized using the hypothermic shock method (2–4 °C). Blood was employed to determine CASP3 activity and the percentage of apoptotic cells with the TUNEL assay, and brains were used to evaluate acetylcholinesterase activity, oxidative damage, and gene expression. After chronic exposure, MET-exposed fish exhibited less swimming activity when compared to control fish. Moreover, compared with the control group, MET significantly inhibited the activity of AChE and induced oxidative damage in the brain of fish. Concerning gene expression, MET significantly upregulated the expression of Nrf1, Nrf2, BAX, p53, BACE1, APP, PSEN1, and downregulated CASP3 and CASP9. Although MET did not overexpress the CASP3 gene, we saw a meaningful rise in the activity of this enzyme in the blood of fish exposed to MET compared to the control group, which we then confirmed by a high number of apoptotic cells in the TUNEL assay. To the best of our understanding, this is the first study that delivers evidence of oxidative impairment, apoptosis, AChE alteration, and overexpression of B- amyloid-related genes in the brain of fish exposed to metformin.

Keywords: AChE inhibition, CASP3 activity, NovelTank test, oxidative damage, TUNEL assay

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Authors: Satria B. Mahathma, Asri Hendrawati

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Background: Diabetes mellitus (DM) is a metabolic disorder syndrome characterized by chronic hyperglycemia. The number of people with diabetes rose from 108 million in 1980 to 422 million in 2014. In general, almost 90% of the prevalence of DM is type 2 DM which marked by insulin resistance and decreased receptor sensitivity. Aside from conventional antidiabetic therapy, the utilization of medicinal plants as alternative medicine has beneficial effects in diabetic patients. Flavonoid contents in radish leaves such as quercetin, pelargonidin, and kaempferol are thought to have antidiabetic activity on decreasing blood glucose levels by tricyclic nucleotide modulation of pancreatic beta cells and ameliorating insulin resistance. This study aimed to determine the effect of variant concentration of radish leaves ethanol extract on blood glucose levels in diabetic rats. Method: This study used pretest-posttest control group design by using 16 male Wistar rats which were induced type-2 diabetic by streptozotocin 60 mg/kg BW-nicotinamide 120 mg/kg BW intraperitoneally. Rats who had developed type-2 DM later divided randomly into 4 groups; negative control received placebo, positive control received glibenclamide 5 mg/kg BW/day, rats intervention I and intervention II received 100% and 50% of radish leaves ethanol extract, respectively. Treatments were administered orally for four weeks. The blood glucose levels were measured using the Enzymatic Colorimetric Test “GOD-PAP”. Data were analyzed by the dependent t-test for pretest-posttest intervention difference and one-way ANOVA followed by post hoc test to determine the significant difference of each treatment to obtain the significant data. Result: The result revealed that intervention group had lower blood glucose levels mean than control group which the lowest was intervention II group (negative control: 540,9 ± 191,7 mg/dl, positive control: 494, 97 ± 64,91 mg/dl, intervention I: 301,92 ± 165,70 mg/dl, and intervention II group: 276,1 ± 139,02 mg/dl. Intervention II group had the highest antidiabetic activity, followed by the intervention I group with the amount of decrease in blood glucose levels were -151,85 ± 77,43 mg/dl and -11,08 ± 186,62 mg/dl, however negative and positive control group didn’t have antidiabetic activity. The dependent t-test result showed there is a significant difference in decreasing blood glucose levels in the intervention II pretest-posttest intervention (p=0,03) while the other group didn’t. Data analyzed by one-way ANOVA also revealed the intervention II group significantly declined blood glucose levels compared to the negative and positive control group (p = 0,033 and p=0,032, respectively). Conclusion: There is a significant effect of radish leaves ethanol extract on blood glucose levels in streptozotocin-nicotinamide-induced diabetic rats with the optimal therapeutic effect at a concentration of 50%.

Keywords: blood glucose levels, medicinal plant, radish leaves, type-2 diabetes mellitus

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Authors: Birendra Kumar Bista, Rhitik Bista, Prafulla Koirala, Lokendra Mandal, Nikrsh Raj Shrestha, Vivek Kattel

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Introduction: Poorly controlled diabetes is associated with cause and poor outcome of stroke. High blood sugar reduces cerebral blood flow, increases intracranial pressure, cerebral edema and neuronal death, especially among patients with poorly controlled diabetes.1 SGLT2 inhibitors are associated with 50% reduction in hemorrhagic stroke compared with placebo. SGLT2 inhibitors decrease cardiovascular events via reducing glucose, blood pressure, weight, arteriosclerosis, albuminuria and reduction of atrial fibrillation.2,3 No study has been documented in low income countries to see the role of post stroke SGLT2 inhibitors on diabetic patients at and after ICU admission. Aims: The aim of the study was to measure the 12 months outcome of diabetic patients with acute stroke admitted in ICU set up with naïve SGLT2 inhibitors add on therapy. Method: It was prospective cohort study carried out in a 250 bedded tertiary neurology care hospital at the province capital Biratnagar Nepal. Diabetic patient with acute stroke admitted in ICU from 1st January 2022 to 31st December 2022 who were not under SGLT2 inhibitors were included in the study. These patients were managed as per hospital protocol. Empagliflozin was added to the alternate enrolled patients. Empagliflozin was continued at the time of discharged and during follow up unless contraindicated. These patients were followed up for 12 months. Outcome measured were mortality, morbidity requiring readmission or hospital visit other than regular follow up, SGLT2 inhibitors related adverse events, neuropsychiatry comorbidity, functional status and biochemical parameters. Ethical permission was taken from hospital administration and ethical board. Results: Among 147 diabetic cases 68 were not treated with empagliflozin whereas 67 cases were started the SGLT2 inhibitors. HbA1c level and one year mortality was significantly low among patients on empaglifozin arm. Over a period of 12 months 427 acute stroke patients were admitted in the ICU. Out of them 44% were female, 61% hypertensive, 34% diabetic, 57% dyslipidemia, 26% smoker and with median age of 45 years. Among 427 cases 4% required neurosurgical interventions and 76% had hemorrhagic CVA. The most common reason for ICU admission was GCS<8 (51%). The median ICU stay was 5 days. ICU mortality was 21% whereas 1 year mortality was 41% with most common reason being pneumonia. Empaglifozin related adverse effect was seen in 11% most commonly lower urinary tract infection in 6%. Conclusion: Empagliflozin can safely be started among acute stroke with better Hba1C control and low mortality outcome compared to treatment without SGLT2 inhibitor.

Keywords: diabetes, ICU, mortality, SGLT2 inhibitors, stroke

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Authors: Yasmeen Jamal Alabdallat, Almutazballlah Bassam Qablan, Hamza Al-Salhi, Salameh Alarood, Ibraheem Alkhawaldeh, Obada Abunar, Adam Abdallah

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Obstructive sleep apnea (OSA) is a disorder caused by the repeated collapse of the upper airway during sleep. It is the most common cause of sleep-related breathing disorder, as OSA can cause loud snoring, daytime fatigue, or more severe problems such as high blood pressure, cardiovascular disease, coronary artery disease, insulin-resistant diabetes, and depression. The hypoglossal nerve stimulator (HNS) is an implantable medical device that reduces the occurrence of obstructive sleep apnea by electrically stimulating the hypoglossal nerve in rhythm with the patient's breathing, causing the tongue to move. This stimulation helps keep the patient's airways clear while they sleep. This systematic review and meta-analysis aimed to assess the clinical outcome of hypoglossal nerve stimulation as a treatment of obstructive sleep apnea. A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials was conducted from inception until August 2022. Studies assessing the following clinical outcomes (Apnea-Hypopnea Index (AHI), Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Oxygen Desaturation Indices (ODI), (Oxygen Saturation (SaO2)) were pooled in the meta-analysis using Review Manager Software. We assessed the quality of studies according to the Cochrane risk-of-bias tool for randomized trials (RoB2), Risk of Bias In Non-randomized Studies - of Interventions (ROBINS-I), and a modified version of NOS for the non-comparative cohort studies.13 Studies (Six Clinical Trials and Seven prospective cohort studies) with a total of 817 patients were included in the meta-analysis. The results of AHI were reported in 11 studies examining OSA 696 patients. We found that there was a significant improvement in the AHI after 12 months of HNS (MD = 18.2 with 95% CI, (16.7 to 19.7; I2 = 0%); P < 0.00001). Further, 12 studies reported the results of ESS after 12 months of intervention with a significant improvement in the range of sleepiness among the examined 757 OSA patients (MD = 5.3 with 95% CI, (4.75 to 5.86; I2 = 65%); P < 0.0001). Moreover, nine studies involving 699 participants reported the results of FOSQ after 12 months of HNS with a significant reported improvement (MD = -3.09 with 95% CI, (-3.41 to 2.77; I2 = 0%); P < 0.00001). In addition, ten studies reported the results of ODI with a significant improvement after 12 months of HNS among the 817 examined patients (MD = 14.8 with 95% CI, (13.25 to 16.32; I2 = 0%); P < 000001). The Hypoglossal Nerve Stimulation showed a significant positive impact on obstructive sleep apnea patients after 12 months of therapy in terms of apnea-hypopnea index, oxygen desaturation indices, manifestations of the behavioral morbidity associated with obstructive sleep apnea, and functional status resulting from sleepiness.

Keywords: apnea, meta-analysis, hypoglossal, stimulation

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Authors: Hossam N. Alhawatmeh, Areen I. Albustanji

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Hemodialysis negatively affects physical and psychological health. Pain, poor sleep quality, and low self-esteem are highly prevalent among patients with end-stage renal disease (ESRD) who receive hemodialysis, significantly increasing mortality and morbidity of those patients. Mind-body interventions (MBI), such as mindfulness meditation, have been recently gaining popularity that improved pain, sleep quality, and self-esteem in different populations. However, to our best knowledge, its effects on these health problems in patients receiving hemodialysis have not been studied in Jordan. Thus, the purpose of the study was to examine the effect of mindfulness meditation on pain, sleep quality, and self-esteem in patients with ESR receiving hemodialysis in Jordan. An experimental repeated-measures, randomized, parallel control design was conducted on (n =60) end-stage renal disease patients undergoing hemodialysis between March and June 2023 in the dialysis center at a public hospital in Jordan. Participants were randomly assigned to the experimental (n =30) and control groups (n =30) using a simple random assignment method. The experimental group practiced mindfulness meditation for 30 minutes three times per week for five weeks during their hemodialysis treatments. The control group's patients continued to receive hemodialysis treatment as usual for five weeks during hemodialysis sessions. The study variables for both groups were measured at baseline (Time 0), two weeks after intervention (Time 1), and at the end of intervention (Time 3). The numerical rating scale (NRS), the Rosenberg Self-Esteem Scale (RSES-M), and the Pittsburgh Sleep Quality Index (PSQI) were used to measure pain, self-esteem, and sleep quality, respectively. SPSS version 25 was used to analyze the study data. The sample was described by frequency, mean, and standard deviation as an appropriate. The repeated measures analysis of variance (ANOVA) tests were run to test the study hypotheses. The results of repeated measures ANOVA (within-subject) revealed that mindfulness meditation significantly decrease pain by the end of the intervention in the experimental group. Additionally, mindfulness meditation improved sleep quality and self-esteem in the experimental group, and these improvements occurred significantly after two weeks of the intervention and at the end of the intervention. The results of repeated measures ANOVA (within and between-subject) revealed that the experimental group, compared to the control group, experienced lower levels of pain and higher levels of sleep quality and self-esteem over time. In conclusion, the results provided substantial evidence supporting the positive impacts of mindfulness meditation on pain, sleep quality, and self-esteem in patients with ESRD undergoing hemodialysis. These results highlight the potential of mindfulness meditation as an adjunctive therapy in the comprehensive care of this patient population. Incorporating mindfulness meditation into the treatment plan for patients receiving hemodialysis may contribute to improved well-being and overall quality of life.

Keywords: hemodialysis, pain, sleep quality, self-esteem, mindfulness

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Authors: Ahmedou Moulaye Idriss, Yahya Tfeil

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Medical imaging technology has become an indispensable tool in many branches of the biomedical, health area, and research and is vitally important for the training of professionals in these fields. It is not only about the tools, technologies, and knowledge provided but also about the community that this training project proposes. In order to be able to raise the level of anatomy teaching in the medical school of Nouakchott in Mauritania, it is necessary and even urgent to facilitate access to modern technology for African countries. The role of technology as a key driver of justifiable development has long been recognized. Anatomy is an essential discipline for the training of medical students; it is a key element for the training of medical specialists. The quality and results of the work of a young surgeon depend on his better knowledge of anatomical structures. The teaching of anatomy is difficult as the discipline is being neglected by medical students in many academic institutions. However, anatomy remains a vital part of any medical education program. When anatomy is presented in various planes medical students approve of difficulties in understanding. They do not increase their ability to visualize and mentally manipulate 3D structures. They are sometimes not able to correctly identify neighbouring or associated structures. This is the case when they have to make the identification of structures related to the caudate lobe when the liver is moved to different positions. In recent decades, some modern educational tools using digital sources tend to replace old methods. One of the main reasons for this change is the lack of cadavers in laboratories with poorly qualified staff. The emergence of increasingly sophisticated mathematical models, image processing, and visualization tools in biomedical imaging research have enabled sophisticated three-dimensional (3D) representations of anatomical structures. In this paper, we report our current experience in the Faculty of Medicine in Nouakchott Mauritania. One of our main aims is to create a local learning community in the fields of anatomy. The main technological platform used in this project is called 3D Slicer. 3D Slicer platform is an open-source application available for free for viewing, analysis, and interaction with biomedical imaging data. Using the 3D Slicer platform, we created from real medical images anatomical atlases of parts of the human body, including head, thorax, abdomen, liver, and pelvis, upper and lower limbs. Data were collected from several local hospitals and also from the website. We used MRI and CT-Scan imaging data from children and adults. Many different anatomy atlases exist, both in print and digital forms. Anatomy Atlas displays three-dimensional anatomical models, image cross-sections of labelled structures and source radiological imaging, and a text-based hierarchy of structures. Open and free online anatomical atlases developed by our anatomy laboratory team will be available to our students. This will allow pedagogical autonomy and remedy the shortcomings by responding more fully to the objectives of sustainable local development of quality education and good health at the national level. To make this work a reality, our team produced several atlases available in our faculty in the form of research projects.

Keywords: anatomy, education, medical imaging, three dimensional

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Authors: Gianluca Castelnuovo, Gian Mauro Manzoni, Giada Pietrabissa, Stefania Corti, Emanuele Giusti, Roberto Cattivelli, Enrico Molinari, Susan Simpson

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Obesity is currently an important public health problem of epidemic proportions (globesity). Moreover Binge Eating Disorder (BED) is typically connected with obesity, even if not occurring exclusively in conjunction with overweight conditions. Typically obesity with BED requires a longer term treatment in comparison with simple obesity. Rehabilitation interventions that aim at improving weight-loss, reducing obesity-related complications and changing dysfunctional behaviors, should ideally be carried out in a multidisciplinary context with a clinical team composed of psychologists, dieticians, psychiatrists, endocrinologists, nutritionists, physiotherapists, etc. Long-term outpatient multidisciplinary treatments are likely to constitute an essential aspect of rehabilitation, due to the growing costs of a limited inpatient approach. Internet-based technologies can improve long-term obesity rehabilitation within a collaborative approach. The new m health (m-health, mobile health) paradigm, defined as clinical practices supported by up to date mobile communication devices, could increase compliance- engagement and contribute to a significant cost reduction in BED and obesity rehabilitation. Five psychological components need to be considered for successful m Health-based obesity rehabilitation in order to facilitate weight-loss.1) Self-monitoring. Portable body monitors, pedometers and smartphones are mobile and, therefore, can be easily used, resulting in continuous self-monitoring. 2) Counselor feedback and communication. A functional approach is to provide online weight-loss interventions with brief weekly or monthly counselor or psychologist visits. 3) Social support. A group treatment format is typically preferred for behavioral weight-loss interventions. 4) Structured program. Technology-based weight-loss programs incorporate principles of behavior therapy and change with structured weekly protocolos including nutrition, exercise, stimulus control, self-regulation strategies, goal-setting. 5) Individually tailored program. Interventions specifically designed around individual’s goals typically record higher rates of adherence and weight loss. Opportunities and limitations of m health approach in clinical psychology for obesity and BED are discussed, taking into account future research directions in this promising area.

Keywords: obesity, rehabilitation, out-patient, new technologies, tele medicine, tele care, m health, clinical psychology, psychotherapy, chronic care management

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers

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Authors: Umair Shoukat Ali, Rashna Hoshang Sukhia, Mubassar Fida

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Introduction: The objective of the study was to compare outcomes in terms of Bleeding index (BI), Gingival Index (GI), and Orthodontic Plaque Index (OPI) with video graphics and plaque disclosing tablets (PDT) versus verbal instructions in adult orthodontic patients undergoing fixed appliance treatment (FAT). Materials and Methods: Adult orthodontic patients have recruited from outpatient orthodontic clinics who fulfilled the inclusion criteria and were randomly allocated to three groups i.e., video, PDT, and verbal groups. We included patients undergoing FAT for six months of both genders with all teeth bonded mesial to first molars having no co-morbid conditions such as rheumatic fever and diabetes mellitus. Subjects who had gingivitis as assessed by Bleeding Index (BI), Gingival Index (GI), and Orthodontic Plaque Index (OPI) were recruited. We excluded subjects having > 2 mm of clinical attachment loss, pregnant and lactating females, any history of periodontal therapy within the last six months, and any consumption of antibiotics or anti-inflammatory drugs within the last one month. Pre- and post-interventional measurements were taken at two intervals only for BI, GI, and OPI. The primary outcome of this trial was to evaluate the mean change in the BI, GI, and OPI in the three study groups. A computer-generated randomization list was used to allocate subjects to one of the three study groups using a random permuted block sampling of 6 and 9 to randomize the samples. No blinding of the investigator or the participants was performed. Results: A total of 99 subjects were assessed for eligibility, out of which 96 participants were randomized as three of the participants declined to be part of this trial. This resulted in an equal number of participants (32) that were analyzed in all three groups. The mean change in the oral hygiene indices score was assessed, and we found no statistically significant difference among the three interventional groups. Pre- and post-interventional results showed statistically significant improvement in the oral hygiene indices for the video and PDT groups. No statistically significant difference for age, gender, and education level on oral hygiene indices were found. Simple linear regression showed that the video group produced significantly higher mean OPI change as compared to other groups. No harm was observed during the trial. Conclusions: Visual aids performed better as compared to the verbal group. Gender, age, and education level had no statistically significant impact on the oral hygiene indices. Longer follow-ups will be required to see the long-term effects of these interventions. Trial Registration: NCT04386421 Funding: Aga Khan University and Hospital (URC 183022)

Keywords: oral hygiene, orthodontic treatment, adults, randomized clinical trial

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Authors: Sima E. Rugarabamu, Mecky I. Matee, Elison N. M. Simon

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Background: In Tanzania bacteriological studies of etiological agents of oro-facial infections are very limited, and very few have investigated anaerobes. The aim of this study was to determine the spectrum of bacterial agents involved in oral and maxillofacial infections in patients attending Muhimbili National Hospital, Dar-es-salaam, Tanzania. Method: This was a hospital based descriptive cross-sectional study that was conducted in the Department of Oral and Maxillofacial Surgery of the Muhimbili National Hospital in Dar es Salaam, Tanzania from 1st January 2014 to 31st August 2014. Seventy (70) patients with various forms of oral and maxillofacial infections who were recruited for the study. The study participants were interviewed using a prepared questionnaire after getting their consent. Pus aspirate was cultured on Blood agar, Chocolate Agar, MacConkey agar and incubated aerobically at 37°C. Imported blood agar was used for anaerobic culture whereby they were incubated at 37°Cin anaerobic jars in an atmosphere of generated using commercial gas-generating kits in accordance with manufacturer’s instructions. Plates were incubated at 37°C for 24 hours (For aerobic culture and 48 hours for anaerobic cultures). Gram negative rods were identified using API 20E while all other isolates were identified by conventional biochemical tests. Antibiotic sensitivity testing for isolated aerobic and anaerobic bacteria was detected by the disk diffusion, agar dilution and E-test using routine and commercially available antibiotics used to treat oral facial infections. Results: This study comprised of 41 (58.5%) males and 29 (41.5%) females with a mean age of 32 years SD +/-15.1 and a range of 19 to 70 years. A total of 161 bacteria strains were isolated from specimens obtained from 70 patients which were an average of 2.3 isolates per patient. Of these 103 were aerobic organism and 58 were strict anaerobes. A complex mix of strict anaerobes and facultative anaerobes accounted for 87% of all infections.The most frequent aerobes isolated was streptococcus spp 70 (70%) followed by Staphylococcus spp 18 (18%). Other organisms such as Klebsiella spp 4 (4%), Proteus spp 5 (5%) and Pseudomonas spp 2 (2%) were also seen. The anaerobic group was dominated by Prevotella spp 25 (43%) followed by Peptostreptococcus spp 18 (31%); other isolates were Pseudomonas spp 2 (1%), black pigmented Pophyromonas spp 4 (5%), Fusobacterium spp 3 (3%) and Bacteroides spp 5 (8%). Majority of these organisms were sensitive to Amoxicillin (98%), Gentamycin (89%), and Ciprofloxacin (100%). A 40% resistance to metronidazole was observed in Bacteroides spp otherwise this drug and others displayed good activity against anaerobes. Conclusions: Oral and maxillofacial facial infections at Muhimbili National Hospital are mostly caused by streptococcus spp and Prevotella spp. Strict anaerobes accounted for 36% of all isolates. The profile of isolates should assist in selecting empiric therapy for infections of the oral and maxillofacial region. Inclusion of antimicrobial agents against anaerobic bacteria is highly recommended.

Keywords: bacteria, oral and maxillofacial infections, antibiotic susceptibility, Tanzania

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Authors: Jyoti Singh, Ranju Bansal

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Fighting pain and inflammation is a common problem faced by physicians while dealing with a wide variety of diseases. Since ancient time nonsteroidal anti-inflammatory agents (NSAIDs) and opioids have been the cornerstone of treatment therapy, however, the usefulness of both these classes is limited due to severe side effects. NSAIDs, which are mainly used to treat mild to moderate inflammatory pain, induce gastric irritation and nephrotoxicity whereas opioids show an array of adverse reactions such as respiratory depression, sedation, and constipation. Moreover, repeated administration of these drugs induces tolerance to the analgesic effects and physical dependence. Further discovery of selective COX-2 inhibitors (coxibs) suggested safety without any ulcerogenic side effects; however, long-term use of these drugs resulted in kidney and hepatic toxicity along with an increased risk of secondary cardiovascular effects. The basic approaches towards inflammation and pain treatment are constantly changing, and researchers are continuously trying to develop safer and effective anti-inflammatory drug candidates for the treatment of different inflammatory conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, psoriasis and multiple sclerosis. Synthetic 3(2H)-pyridazinones constitute an important scaffold for drug discovery. Structure-activity relationship studies on pyridazinones have shown that attachment of a lactam at N-2 of the pyridazinone ring through a methylene spacer results in significantly increased anti-inflammatory and analgesic properties of the derivatives. Further introduction of the heterocyclic ring at lactam nitrogen results in improvement of biological activities. Keeping in mind these SAR studies, a new series of compounds were synthesized as shown in scheme 1 and investigated for anti-inflammatory, analgesic, anti-platelet activities and docking studies. The structures of newly synthesized compounds have been established by various spectroscopic techniques. All the synthesized pyridazinone derivatives exhibited potent anti-inflammatory and analgesic activity. Homoveratryl substituted derivative was found to possess highest anti-inflammatory and analgesic activity displaying 73.60 % inhibition of edema at 40 mg/kg with no ulcerogenic activity when compared to standard drugs indomethacin. Moreover, 2-substituted-4-benzo[d][1,3]dioxole-6-phenylpyridazin-3(2H)-ones derivatives did not produce significant changes in bleeding time and emerged as safe agents. Molecular docking studies also illustrated good binding interactions at the active site of the cyclooxygenase-2 (hCox-2) enzyme.

Keywords: anti-inflammatory, analgesic, pyridazin-3(2H)-one, selective COX-2 inhibitors

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Authors: N. Garrós, P. Bustos, N. Beirampour, R. Mohammadi, M. Mallandrich, A.C. Calpena, H. Colom

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Atopic dermatitis (AD) is a persistent skin condition characterized by chronic inflammation caused by an autoimmune response. It is a prevalent clinical issue that requires continual treatment to enhance the patient's quality of life. Systemic therapy often involves the use of glucocorticoids or immunosuppressants to manage symptoms. Our objective was to create and assess topical liposomal formulations containing Baricitinib (BNB), a reversible inhibitor of Janus-associated kinase (JAK), which is involved in various immune responses. These formulations were intended to address flare-ups and improve treatment outcomes for AD. We created three distinct liposomal formulations by combining different amounts of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC), cholesterol (CHOL), and ceramide (CER): (i) pure POPC, (ii) POPC mixed with CHOL (at a ratio of 8:2, mol/mol), and (iii) POPC mixed with CHOL and CER (at a ratio of 3.6:2.4:4.0 mol/mol/mol). We conducted various tests to determine the formulations' skin tolerance, irritancy capacity, and their ability to cause erythema and edema on altered skin. We also assessed the transepidermal water loss (TEWL) and skin hydration of rabbits to evaluate the efficacy of the formulations. Histological analysis, the HET-CAM test, and the modified Draize test were all used in the evaluation process. The histological analysis revealed that liposome POPC and POPC:CHOL avoided any damage to the tissues structures. The HET-CAM test showed no irritation effect caused by any of the three liposomes, and the modified Draize test showed a good Draize score for erythema and edema. Liposome POPC effectively counteracted the impact of xylol on the skin, and no erythema or edema was observed during the study. TEWL values were constant for all the liposomes with similar values to the negative control (within the range 8 - 15 g/h·m2, which means a healthy value for rabbits), whereas the positive control showed a significant increase. The skin hydration values were constant and followed the trend of the negative control, while the positive control showed a steady increase during the tolerance study. In conclusion, the developed formulations containing BNB exhibited no harmful or irritating effects, they did not demonstrate any irritant potential in the HET-CAM test and liposomes POPC and POPC:CHOL did not cause any structural alteration according to the histological analysis. These positive findings suggest that additional research is necessary to evaluate the efficacy of these liposomal formulations in animal models of the disease, including mutant animals. Furthermore, before proceeding to clinical trials, biochemical investigations should be conducted to better understand the mechanisms of action involved in these formulations.

Keywords: baricitinib, HET-CAM test, histological study, JAK inhibitor, liposomes, modified draize test

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Authors: V. K. Rajaletchumy, S. L. Chia, M. I. Setyawati, M. S. Muthu, S. S. Feng, D. T. Leong

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Triple negative breast cancers (TNBC) can be classified as one of the most aggressive with a high rate of local recurrences and systematic metastases. TNBCs are insensitive to existing hormonal therapy or targeted therapies such as the use of monoclonal antibodies, due to the lack of oestrogen receptor (ER) and progesterone receptor (PR) and the absence of overexpression of human epidermal growth factor receptor 2 (HER2) compared with other types of breast cancers. The absence of targeted therapies for selective delivery of therapeutic agents into tumours, led to the search for druggable targets in TNBC. In this study, we developed a targeted micellar system of cetuximab-conjugated micelles of D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) for targeted delivery of docetaxel as a model anticancer drug for the treatment of TNBCs. We examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. The targeting micelles were found preferentially accumulated in tumours immediately after the administration of the micelles compare to normal tissue. The fluorescence signal gradually increased up to 12 h at the tumour site and sustained for up to 24 h, reflecting the increases in targeted micelles (TPFC) micelles in MDA-MB-231/Luc cells. In comparison, for the non-targeting micelles (TPF), the fluorescence signal was evenly distributed all over the body of the mice. Only a slight increase in fluorescence at the chest area was observed after 24 h post-injection, reflecting the moderate uptake of micelles by the tumour. The successful delivery of docetaxel into tumour by the targeted micelles (TPDC) exhibited a greater degree of tumour growth inhibition than Taxotere® after 15 days of treatment. The ex vivo study has demonstrated that tumours treated with targeting micelles exhibit enhanced cell cycle arrest and attenuated proliferation compared with the control and with those treated non-targeting micelles. Furthermore, the ex vivo investigation revealed that both the targeting and non-targeting micellar formulations shows significant inhibition of cell migration with migration indices reduced by 0.098- and 0.28-fold, respectively, relative to the control. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGF-overexpressing MDA-MB-231 tumours.

Keywords: biodegradable polymers, cancer nanotechnology, drug targeting, molecular biomaterials, nanomedicine

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Authors: Nurlan Smagulov, Aiman Konkabayeva, Akerke Sadykova, Arailym Serik

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Introduction. Adverse environmental factors do not immediately lead to pathological changes in the body. They can exert the growth of pre-pathology characterized by shifts in physiological, biochemical, immunological and other indicators of the body state. These disorders are unstable, reversible and indicative of body reactions. There is an opportunity to objectively judge the internal structure of the adaptive body reactions at the level of individual organs and systems. In order to obtain a stable response of the body to the chronic effects of unfavorable environmental factors of low intensity (compared to production environment factors), a time called the «lag time» is needed. The obtained results without considering this factor distort reality and, for the most part, cannot be a reliable statement of the main conclusions in any work. A technique is needed to reduce methodological errors and combine mathematical logic using statistical methods and a medical point of view, which ultimately will affect the obtained results and avoid a false correlation. Objective. Development of a methodology for assessing and predicting the environmental factors impact on the population health considering the «lag time.» Methods. Research objects: environmental and population morbidity indicators. The database on the environmental state was compiled from the monthly newsletters of Kazhydromet. Data on population morbidity were obtained from regional statistical yearbooks. When processing static data, a time interval (lag) was determined for each «argument-function» pair. That is the required interval, after which the harmful factor effect (argument) will fully manifest itself in the indicators of the organism's state (function). The lag value was determined by cross-correlation functions of arguments (environmental indicators) with functions (morbidity). Correlation coefficients (r) and their reliability (t), Fisher's criterion (F) and the influence share (R2) of the main factor (argument) per indicator (function) were calculated as a percentage. Results. The ecological situation of an industrially developed region has an impact on health indicators, but it has some nuances. Fundamentally opposite results were obtained in the mathematical data processing, considering the «lag time». Namely, an expressed correlation was revealed after two databases (ecology-morbidity) shifted. For example, the lag period was 4 years for dust concentration, general morbidity, and 3 years – for childhood morbidity. These periods accounted for the maximum values of the correlation coefficients and the largest percentage of the influencing factor. Similar results were observed in relation to the concentration of soot, dioxide, etc. The comprehensive statistical processing using multiple correlation-regression variance analysis confirms the correctness of the above statement. This method provided the integrated approach to predicting the degree of pollution of the main environmental components to identify the most dangerous combinations of concentrations of leading negative environmental factors. Conclusion. The method of assessing the «environment-public health» system (considering the «lag time») is qualitatively different from the traditional (without considering the «lag time»). The results significantly differ and are more amenable to a logical explanation of the obtained dependencies. The method allows presenting the quantitative and qualitative dependence in a different way within the «environment-public health» system.

Keywords: ecology, morbidity, population, lag time

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Authors: Huidan Yu, Anurag Deb, Rou Chen, I-Wen Wang

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The use of left ventricle assist devices (LVADs) in patients with heart failure has been a proven and effective therapy for patients with severe end-stage heart failure. Due to the limited availability of suitable donor hearts, LVADs will probably become the alternative solution for patient with heart failure in the near future. While the LVAD is being continuously improved toward enhanced performance, increased device durability, reduced size, a better understanding of implantation management becomes critical in order to achieve better long-term blood supplies and less post-surgical complications such as thrombi generation. Important issues related to the LVAD implantation include the location of outflow grafting (OG), the angle of the OG, the combination between LVAD and native heart pumping, uniform or pulsatile flow at OG, etc. We have hypothesized that an optimal implantation of LVAD is patient specific. To test this hypothesis, we employ a novel in-house computational modeling technique, named InVascular, to conduct a systematic evaluation of cardiac output at aortic arch together with other pertinent hemodynamic quantities for each patient under various implantation scenarios aiming to get an optimal implantation strategy. InVacular is a powerful computational modeling technique that integrates unified mesoscale modeling for both image segmentation and fluid dynamics with the cutting-edge GPU parallel computing. It first segments the aortic artery from patient’s CT image, then seamlessly feeds extracted morphology, together with the velocity wave from Echo Ultrasound image of the same patient, to the computation model to quantify 4-D (time+space) velocity and pressure fields. Using one NVIDIA Tesla K40 GPU card, InVascular completes a computation from CT image to 4-D hemodynamics within 30 minutes. Thus it has the great potential to conduct massive numerical simulation and analysis. The systematic evaluation for one patient includes three OG anastomosis (ascending aorta, descending thoracic aorta, and subclavian artery), three combinations of LVAD and native heart pumping (1:1, 1:2, and 1:3), three angles of OG anastomosis (inclined upward, perpendicular, and inclined downward), and two LVAD inflow conditions (uniform and pulsatile). The optimal LVAD implantation is suggested through a comprehensive analysis of the cardiac output and related hemodynamics from the simulations over the fifty-four scenarios. To confirm the hypothesis, 5 random patient cases will be evaluated.

Keywords: graphic processing unit (GPU) parallel computing, left ventricle assist device (LVAD), lumped-parameter model, patient-specific computational hemodynamics

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Authors: Parichehr Sharifi, Konrad Reschke, Hans-Liudger Dienel

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Psychological intervention generally targets changes in attitudes and behavior. Working with DUIs is part of traffic psychologists’ work. The primary goal of this field is to reduce the probability of re-conspicuous of the delinquent driver. One of these measurements in Germany is IFT courses for DUI s. The IFT course was designed by the Institute for Therapy Research. Participants are drivers who have fallen several times or once with a blood alcohol concentration of 1.6 per mill and who have completed a medical-psychological assessment (MPU) with the result of the course recommendation. The course covers four sessions of 3.5 hours each (1 hour / 60 m) and in a period of 3 to 4 weeks in the group discussion. This work analyzes interventions for the rehabilitation of DUI (Drunk Drivers offenders) offenders in groups under the aspect of activating psychological resources. From the aspect of sustainability, they should also have long-term consequences for the maintenance of unproblematic driving behavior in terms of the activation of resources. It is also addressing a selected consistency-theory-based intervention effect, activating psychological resources. So far, this has only been considered in the psychotherapeutic field but never in the field of traffic psychology. The methodology of this survey is one qualitative and three quantitative. In four sub-studies, it will be examined which measurements can determine the resources and how traffic psychological interventions can strengthen resources. The results of the studies have the following implications for traffic psychology research and practice: (1) In the field of traffic psychology intervention for the restoration of driving fitness, it can be stated that aspects of resource activation in this work have been investigated for the first time by qualitative and quantitative methods. (2) The resource activation could be confirmed based on the determined results as an effective factor of traffic psychological intervention. (3) Two sub-studies show a range of resources and resource activation options that must be given greater emphasis in traffic psychology interventions: - Social resource activation - improvement of the life skills of participants - Reactivation of existing social support options - Re-experiencing self-esteem, self-assurance, and acceptance of traffic-related behaviors. (4) In revising the IFT-§70 course, as well as other courses on recreating aptitude for DUI, new traffic-specific resource-enabling interventions against alcohol abuse should be developed to further enhance the courses through motivational, cognitive, and behavioral effects of resource activation, Resource-activating interventions can not only be integrated into behavioral group interventions but can also be applied in psychodynamic, psychodynamic (individual psychological) and other contexts of individual traffic psychology. The results are indicative but clearly show that personal resources can be strengthened through traffic psychology interventions. In the research, practice, training, and further education of traffic psychology, the aspect of primary resource activation (Grawe, 1999), therefore, always deserves the greatest attention for the rehabilitation of DUIs and Traffic safety.

Keywords: traffic safety, psychological resources, activating of resources, intervention programs for alcohol offenders, empowerment

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Authors: Elisabetta Cianfanelli, Maria Claudia Coppola, Margherita Tufarelli

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Design practices throughout history return a critical understanding of society since they always conveyed values and meanings aimed at (re)framing reality by acting in everyday life: here, design gains cultural and normative character, since its artifacts, services, and environments hold the power to intercept, influence and inspire thoughts, behaviors, and relationships. In this sense, design can be persuasive, engaging in the production of worlds and, as such, acting in the space between poietics and politics so that chasing preferable futures and their aesthetic strategies becomes a matter full of political responsibility. This resonates with contemporary landscapes of radical interdependencies challenging designers to focus on complex socio-technical systems and to better support values such as equality and justice for both humans and nonhumans. In fact, it is in times of crisis and structural uncertainty that designers turn into visionaries at the service of society, envisioning scenarios and dwelling in the territories of imagination to conceive new fictions and frictions to be added to the thickness of the real. Here, design’s main tasks are to develop options, to increase the variety of choices, to cultivate its role as scout, jester, agent provocateur for the public, so that design for transformation emerges, making an explicit commitment to society, furthering structural change in a proactive and synergic manner. However, the exploration of possible futures is both a trap and a trampoline because, although it embodies a radical research tool, it raises various challenges when the design process goes further in the translation of such vision into an artefact - whether tangible or intangible -, through which it should deliver that bit of future into everyday experience. Today designers are making up new tools and practices to tackle current wicked challenges, combining their approaches with other disciplinary domains: futuring through design, thus, rises from research strands like speculative design, design fiction, and critical design, where the blending of design approaches and futures thinking brings an action-oriented and product-based approach to strategic insights. The contribution positions at the intersection of those approaches, aiming at discussing design’s tools of inquiry through which it is possible to grasp the agency of imagined futures into present time. Since futures are not remote, they actively participate in creating path-dependent decisions, crystallized into designed artifacts par excellence, prototypes, and their conceptual other, provotypes: with both being unfinished and multifaceted, the first ones are effective in reiterating solutions to problems already framed, while the second ones prove to be useful when the goal is to explore and break boundaries, bringing closer preferable futures. By focusing on some provotypes throughout history which challenged markets and, above all, social and cultural structures, the contribution’s final aim is understanding the knowledge produced by provotypes, understood as design spaces where designs’s humanistic side might help developing a deeper sensibility about uncertainty and, most of all, the unfinished feature of societal artifacts, whose experimentation would leave marks and traces to build up f(r)ictions as vital sparks of plurality and collective life.

Keywords: speculative design, provotypes, design knowledge, political theory

Procedia PDF Downloads 113