Search results for: clinical staff

Authors: Mazoun Nasser Rashid Al Kharusi, Nada Al Siyabi

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Objectives: The main aim of this study is to Find the rate of susceptibility of ESBL E. coli causing UTI to oral antibiotics. Secondary objectives: Prevalence of ESBL E. coli from community urine samples, identify the best empirical oral antibiotics with the least resistance rate for UTI and identify alternative oral antibiotics for testing and utilization. Methods: This study is a retrospective descriptive study of the last three years in five major hospitals in Oman (Khowla Hospital, AN’Nahdha Hospital, Rustaq Hospital, Nizwa Hospital, and Ibri Hospital) equipped with a microbiologist. Inclusion criteria include all eligible outpatient urine culture isolates, excluding isolates from admitted patients with hospital-acquired urinary tract infections. Data was collected through the MOH database. The MOH hospitals are using different types of testing, automated methods like Vitek2 and manual methods. Vitek2 machine uses the principle of the fluorogenic method for organism identification and a turbidimetric method for susceptibility testing. The manual method is done by double disc diffusion for identifying ESBL and the disc diffusion method is for antibiotic susceptibility. All laboratories follow the clinical laboratory science institute (CLSI) guidelines. Analysis was done by SPSS statistical package. Results: Total urine cultures were (23048). E. coli grew in (11637) 49.6% of the urine, whereas (2199) 18.8% of those were confirmed as ESBL. As expected, the resistance rate to amoxicillin and cefuroxime is 100%. Moreover, the susceptibility of those ESBL-producing E. coli to nitrofurantoin, trimethoprim+sulfamethoxazole, ciprofloxacin and amoxicillin-clavulanate is progressing over the years; however, still low. ESBL E. coli was predominating in the female gender and those aged 66-74 years old throughout all the years. Other oral antibiotic options need to be explored and tested so that we add to the pool of oral antibiotics for ESBL E. coli causing UTI in the community. Conclusion: High rate of ESBL E. coli in urine from the community. The high resistance rates to oral antibiotics highlight the need for alternative treatment options for UTIs caused by these bacteria. Further research is needed to identify new and effective treatments for UTIs caused by ESBL-E. Coli.

Keywords: UTI, ESBL, oral antibiotics, E. coli, susceptibility

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Authors: Dina Siniora, Jasia Baig

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During the past few decades, the healthcare system has undergone profound changes in their healthcare decision-making competencies and moral aptitudes due to the vast advancement in technology, clinical skills, and scientific knowledge. Healthcare decision-making deals with morally contentious dilemmas ranging from illness, life and death judgments that require sensitivity and awareness towards the patient’s preferences while taking into consideration medicine’s abilities and boundaries. As the ever-evolving field of medicine continues to become more scientifically and morally multifarious; physicians and the hospital administrators increasingly rely on ethics committees to resolve problems that arise in everyday patient care. The role and latitude of responsibilities of ethics committees which includes being dispute intermediaries, moral analysts, policy educators, counselors, advocates, and reviewers; suggest the importance and effectiveness of a fully integrated committee. Despite achievements on Integrated Ethics and progress in standards and competencies, there is an imminent necessity for further improvement in quality within ethics consultation services in areas of credentialing, professionalism and standards of quality, as well as the quality of healthcare throughout the system. These concerns can be resolved first by collecting data about particular quality gaps and comprehend the level to which ethics committees are consistent with newly published ASBH quality standards. Policymakers should pursue improvement strategies that target both academic bioethics community and major stakeholders at hospitals, who directly influence ethics committees. This broader approach oriented towards education and intervention outcome in conjunction with preventive ethics to address disparities in quality on a systematic level. Adopting tools for improving competencies and processes within ethics consultation by implementing a credentialing process, upholding normative significance for the ASBH core competencies, advocating for professional Code of Ethics, and further clarifying the internal structures will improve productivity, patient satisfaction, and institutional integrity. This cannot be systemically achieved without a written certification exam for HCEC practitioners, credentialing and privileging HCEC practitioners at the hospital level, and accrediting HCEC services at the institutional level.

Keywords: ethics consultation, hospital, medical ethics, quality

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Authors: Lakshmi Sujeesh, Aaron Ramzeen, Ricky Ziming Guo, Abhishek Agrawal

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Introduction: Range of motion (ROM) is often measured by physiotherapists using hand-held goniometer as part of mobility assessment for diagnosis. Due to the nature of hand-held goniometer measurement procedure, readings often tend to have some variations depending on the physical therapist taking the measurements (Riddle et al.). This study aims to validate computer vision software readings against goniometric measurements for quick and consistent ROM measurements to be taken by clinicians. The use of this computer vision software hopes to improve the future of musculoskeletal space with more efficient diagnosis from recording of patient’s ROM with minimal human error across different physical therapists. Methods: Using the hand-held long arm goniometer measurements as the “gold-standard”, healthy study participants (n = 20) were made to perform 4 exercises: Front elevation, Abduction, Internal Rotation, and External Rotation, using both arms. Assessment of active ROM using computer vision software at different angles set by goniometer for each exercise was done. Interclass Correlation Coefficient (ICC) using 2-way random effects model, Box-Whisker plots, and Root Mean Square error (RMSE) were used to find the degree of correlation and absolute error measured between set and recorded angles across the repeated trials by the same rater. Results: ICC (2,1) values for all 4 exercises are above 0.9, indicating excellent reliability. Lowest overall RMSE was for external rotation (5.67°) and highest for front elevation (8.00°). Box-whisker plots showed have showed that there is a potential zero error in the measurements done by the computer vision software for abduction, where absolute error for measurements taken at 0 degree are shifted away from the ideal 0 line, with its lowest recorded error being 8°. Conclusion: Our results indicate that the use of computer vision software is valid and reliable to use in clinical settings by physiotherapists for measuring shoulder ROM. Overall, computer vision helps improve accessibility to quality care provided for individual patients, with the ability to assess ROM for their condition at home throughout a full cycle of musculoskeletal care (American Academy of Orthopaedic Surgeons) without the need for a trained therapist.

Keywords: physiotherapy, frozen shoulder, joint range of motion, computer vision

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Authors: Anna Tokajuk, Agnieszka Zakrzeska, Ewa Chabielska, Halina Car

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Whey is a by-product generated mainly in the production of cheese and casein. Powder forms of whey are used widely in the food industry as well as a high-protein food for infants, for convalescents, by athletes and especially by bodybuilders to increase muscle mass during exercise. Whey protein concentrate-80 (WPC-80) is a source of bioactive peptides with beneficial effects on the cardiovascular system. It is known that whey proteins health beneficial properties include antidiabetic, blood pressure lowering, improving cardiovascular system function, antibacterial, antiviral and other effects. To study its influence on the development of thrombosis, venous thrombosis model was performed according to the protocol featured by Reyers with modification by Chabielska and Gromotowicz. Male Wistar-Crl: WI (Han) rats from researched groups were supplemented with two doses of WPC-80 (0.3 or 0.5 g/kg) for 7, 14 or 21 days and after these periods, one-hour venous thrombosis model was performed. Control group received 0.9 % NaCl solution and was sham operated. The statistical significance of results was computed by Mann – Whitney’s test. We observed that thrombus weight was decreased in animals obtaining WPC-8080 and that was statistically significant in 14 and 21-day supplemented groups. Blood count parameters did not differ significantly in rats with and without thrombosis induction whether they were fed with WPC-80 or not. Moreover, the number of platelets (PLT) was within the normal range in each group. The examined coagulation parameters in rats of the control groups were within normal limits. After WPC-80 supplementation there was the tendency to prolonged activated partial thromboplastin time (aPTT), but in comparison, the results did not turn out significant. In animals that received WPC-80 0.3 g·kg-1 for 21 days with and without induced thrombosis, prothrombin time (PT) and an international normalized ratio (INR) was somewhat decreased, remaining within the normal range, but the nature and significance of this observation are beyond the framework of the current study. Additionally, fibrinogen and thrombin time (TT) did not differ significantly between groups. Therefore the exact effect of WPC-80 on coagulation system is still elusive and requires further thorough research including mechanisms of action. Determining the potential clinical application of WPC-80 requires the selection of the optimal dose and duration of supplementation.

Keywords: antithrombotic, rats, venous thrombosis, WPC-80

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Authors: Mmamapudi Kubjane, Natacha Berkowitz, Rene Goliath, Naomi S. Levitt, Robert J. Wilkinson, Tolu Oni

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Background: South Africa remains a high tuberculosis (TB) burden country globally and the burden of diabetes – a TB risk factor is growing rapidly. As an infectious disease, TB also induces transient hyperglycaemia. Therefore, screening for diabetes in newly diagnosed tuberculosis patients may result in misclassification of transient hyperglycaemia as diabetes. Objective: The objective of this study was to determine and compare the prevalence of hyperglycaemia (diabetes and impaired glucose regulation (IGR)) in TB patients and to assess the cross-sectional association between TB and hyperglycaemia at enrolment and after three months of follow-up. Methods: Consecutive adult TB and non-TB participants presenting at a TB clinic in Cape Town were enrolled in this cross-sectional study and follow-up between July 2013 and August 2015. Diabetes was defined as self-reported diabetes, fasting plasma glucose (FPG) ≥ 7.0 mmol·L⁻¹ or glycated haemoglobin (HbA1c) ≥ 6.5%. IGR was defined as FPG 5.5– < 7.0 mmol·L⁻¹ or HbA1c 5.7– < 6.5%. TB patients initiated treatment. After three months, all participants were followed up and screened for diabetes again. The association between TB and hyperglycaemia was assessed using logistic regression adjusting for potential confounders including sex, age, income, hypertension, waist circumference, previous prisoner, marital status, work status, HIV status. Results: Diabetes screening was performed in 852 participants (414 TB and 438 non-TB) at enrolment and in 639 (304 TB and 335 non-TB) at three-month follow-up. The prevalence of HIV-1 infection was 69.6% (95% confidence interval (CI), 64.9–73.8 %) among TB patients, and 58.2% (95% CI, 53.5–62.8 %) among the non-TB participants. Glycaemic levels were much higher in TB patients than in the non-TB participants but decreased over time. Among TB patients, the prevalence of IGR was 65.2% (95% CI 60.1 - 69.9) at enrollment and 21.5% (95% CI 17.2-26.5) at follow-up; and was 50% (45.1 - 54.94) and 32% (95% CI 27.9 - 38.0) respectively, among non-TB participants. The prevalence of diabetes in TB patients was 12.5% (95% CI 9.69 – 16.12%) at enrolment and 9.2% (95% CI, 6.43–13.03%) at follow-up; and was 10.04% (95% CI, 7.55–13.24%) and 8.06% (95% CI, 5.58–11.51) respectively, among non-TB participants. The association between TB and IGT was significant at enrolment (adjusted odds ratio (OR) 2.26 (95% CI, 1.55-3.31) but disappeared at follow-up 0.84 (0.53 - 1.36). However, the TB-diabetes association remained positive and significant both at enrolment (2.41 (95% CI, 1.3-4.34)) and follow-up (OR 3.31 (95% CI, 1.5 - 7.25)). Conclusion: Transient hyperglycaemia exists during tuberculosis. This has implications on diabetes screening in TB patients and suggests a need for diabetes confirmation tests during or after TB treatment. Nonetheless, the association between TB and diabetes noted at enrolment persists at 3 months highlighting the importance of diabetes control and prevention for TB control. Further research is required to investigate the impact of hyperglycaemia (transient or otherwise) on TB outcomes to ascertain the clinical significance of hyperglycemia at enrolment.

Keywords: diabetes, impaired glucose regulation, transient hyperglycaemia, tuberculosis

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Authors: Johnson C. Y. Pang, Bo Peng, Kara K. L. Reeves, Allan C. L. Fud

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Objective: Dry needling (DN) has long been used as a treatment method for various musculoskeletal pain conditions. However, the evidence level of the studies was low due to the limitations of the methodology. Lack of randomization and inappropriate blinding is potentially the main sources of bias. A method that can differentiate clinical results due to the targeted experimental procedure from its placebo effect is needed to enhance the validity of the trial. Therefore, this study aimed to validate the method as a placebo ultrasound(US)-guided DN for patients with knee osteoarthritis (KOA). Design: This is a randomized controlled trial (RCT). Ninety subjects (25 males and 65 females) aged between 51 and 80 (61.26 ± 5.57) with radiological KOA were recruited and randomly assigned into three groups with a computer program. Group 1 (G1) received real US-guided DN, Group 2 (G2) received placebo US-guided DN, and Group 3 (G3) was the control group. Both G1 and G2 subjects received the same procedure of US-guided DN, except the US monitor was turned off in G2, blinding the G2 subjects to the incorporation of faux US guidance. This arrangement created the placebo effect intended to permit comparison of their results to those who received actual US-guided DN. Outcome measures, including the visual analog scale (VAS) and Knee injury and Osteoarthritis Outcome Score (KOOS) subscales of pain, symptoms, and quality of life (QOL), were analyzed by repeated measures analysis of covariance (ANCOVA) for time effects and group effects. The data regarding the perception of receiving real US-guided DN or placebo US-guided DN were analyzed by the chi-squared test. The missing data were analyzed with the intention-to-treat (ITT) approach if more than 5% of the data were missing. Results: The placebo US-guided DN (G2) subjects had the same perceptions as the use of real US guidance in the advancement of DN (p<0.128). G1 had significantly higher pain reduction (VAS and KOOS-pain) than G2 and G3 at 8 weeks (both p<0.05) only. There was no significant difference between G2 and G3 at 8 weeks (both p>0.05). Conclusion: The method with the US monitor turned off during the application of DN is credible for blinding the participants and allowing researchers to incorporate faux US guidance. The validated placebo US-guided DN technique can aid in investigations of the effects of US-guided DN with short-term effects of pain reduction for patients with KOA. Acknowledgment: This work was supported by the Caritas Institute of Higher Education [grant number IDG200101].

Keywords: ultrasound-guided dry needling, dry needling, knee osteoarthritis, physiotheraphy

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Authors: H. Jeries, N. Volkova, C. G. Iglesias, M. Najjar, M. Rosenblat, M. Aviram, T. Hayek

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Background: Synthetic forms of glucocorticoids (e.g., prednisone, prednisolone) are anti-inflammatory drugs which are widely used in clinical practice. The role of glucocorticoids (GCs) in cardiovascular diseases including atherosclerosis is highly controversial, and their impact on macrophage foam cell formation is still unknown. Our aim was to investigate the effects of prednisone or its active metabolite, prednisolone, on macrophage oxidative stress and lipid metabolism using in-vivo, ex-vivo and in-vitro systems. Methods: The in-vivo study included C57BL/6 mice which were intraperitoneally injected with prednisone or prednisolone (5mg/kg) for 4 weeks, followed by lipid metabolism analyses in the mice aorta, and in peritoneal macrophages (MPM). In the ex-vivo study, we analyzed the effect of serum samples obtained from 9 healthy volunteers before or after treatment with oral prednisone (20mg for 5 days), on J774A.1 macrophage atherogenicity. In-vitro studies were conducted using J774A.1 macrophages, human monocyte derived macrophages (HMDM) and fibroblasts. Cells were incubated with increasing concentrations (0-200 ng/ml) of prednisone or prednisolone, followed by determination of cellular oxidative status, triglyceride and cholesterol metabolism. Results: Prednisone or prednisolone treatment resulted in a significant reduction in triglycerides and mainly in cholesterol cellular accumulation in MPM or in J774A.1 macrophages incubated with human serum. Similar resulted were noted in HMDM or in J774A.1 macrophages which were directly incubated with the GCs. These effects were associated with GCs inhibitory effect on triglycerides and cholesterol biosynthesis rates, throughout downregulation of diacylglycerol acyltransferase1 (DGAT1) expression, and of the sterol regulatory element binding protein (SREBP2) and HMGCR expression, respectively. In parallel to prednisone or prednisolone induced reduction in macrophage triglyceride content, paraoxonase 2 (PON2) expression was significantly upregulated. GCs-induced reduction of cellular triglyceride and cholesterol mass was mediated by the GCs receptors on macrophages since the GCs receptor antagonist (RU 486) abolished these effects. In fibroblasts, unlike macrophages, prednisone or prednisolone showed no anti-atherogenic effects. Conclusions: Prednisone or prednisolone are anti-atherogenic since they protected macrophages from lipid accumulation and foam cell formation.

Keywords: atherosclerosis, cholesterol, foam cell, macrophage, prednisone, prednisolone, triglycerides

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Authors: Tiago Sigal Linhares, Ana Amélia Nascimento da Silva Bones, Juliana Miola, McArthur Alexander Barrow, Airton Tetelbom Stein

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Introduction: As a result of increased globalization and changing migration trends, it is expected that a significant portion of People Living with HIV/AIDS (PLWHA) will change their place of residence over time. In order to provide better health care, monitor the HIV epidemic and plan urban public health care and policies, there is a growing need to formulate a strategy for monitoring PLWHA care, location and migration patterns. The Porto Alegre District is characterized by a high prevalence of PLWHA and is considered one of the epicenters of HIV epidemic in Latin America. Objectives: The aim of this study is to create a digital and easily editable map in order to create a visual representation of the location of PLWHA and to monitor their migration within the city and the country in an effort to promote longitudinal care. Methods: This Experience Report used Google Maps Map Creator to generate an active digital map showing the location and changes in residence of 165 PLWHA who received care at two Primary Health Care (PHC) clinics, which attended an estimated population of five thousand patients, in downtown Porto Alegre over the last four years. Their current addresses were discovered in the unified Brazilian health care system digital records (e-SUS) and updated on the map. Results: A digital map with PLWHA current residence location was created. It was possible to demonstrate visually areas with a large concentration of PLWHA and the migration of the population within the city as wells as other cities, regions and states. Conclusions: An easily reproducible and free map could aid in PLWHA monitoring, urban public health planning, target interventions and situational diagnosis. Moreover, a visual representation of PLWHA location and migration could help bring more attention and investments to areas with geographic inequities or higher prevalence of PLWHA. It also enables notification of local PHC units of monitored patients inside their area, which are in clinical risk or with treatment abandonment through active case findings, improving the care of PLWHA.

Keywords: health care, medical public health, theoretical and conceptual innovations, urban public health

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Authors: Madhusudana S. N., Reeta Mani, Ashwini S. Satishchandra P., Netravati, Udhani V., Fiaz A., Karande S.

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Rabies is an acute encephalitis which is considered 100% fatal despite occasional reports of survivors. However, in recent times more cases of human rabies survivors are being reported. In the last 5 years, there are six laboratories confirmed human rabies survivors in India alone. All cases were children below 15 years and all contracted the disease by dog bites. All of them also had received the full or partial course of rabies vaccination and 4 out of 6 had also received rabies immunoglobulin. All cases were treated in intensive care units in hospitals at Bangalore, Mumbai, Chandigarh, Lucknow and Goa. We report here the results of immunological and virological studies conducted at our laboratory on these patients. The clinical samples that were obtained from these patients were Serum, CSF, nuchal skin biopsy and saliva. Serum and CSF samples were subjected to standard RFFIT for estimation of rabies neutralizing antibodies. Skin biopsy, CSF and saliva were processed by TaqMan real-time PCR for detection of viral RNA. CSF, saliva and skin homogenates were also processed for virus isolation by inoculation of suckling mice. The PBMCs isolated from fresh blood was subjected to ELISPOT assay to determine the type of immune response (Th1/Th2). Both CSF and serum were also investigated for selected cytokines by Luminex assay. The level of antibodies to virus G protein and N protein were determined by ELISA. All survivors had very high titers of RVNA in serum and CSF 100 fold higher than non-survivors and vaccine controls. A five-fold rise in titer could be demonstrated in 4 out of 6 patients. All survivors had a significant increase in antibodies to G protein in both CSF and serum when compared to non-survivors. There was a profound and robust Th1 response in all survivors indicating that interferon gamma could play an important factor in virus clearance. We could isolate viral RNA in only one patient four years after he had developed symptoms. The partial N gene sequencing revealed 99% homology to species I strain prevalent in India. Levels of selected cytokines in CSF and serum did not reveal any difference between survivors and non-survivors. To conclude, survival from rabies is mediated by virus-specific immune responses of the host and clearance of rabies virus from CNS may involve the participation of both Th2 and Th1 immune responses.

Keywords: rabies, rabies treatment, rabies survivors, immune reponse in rabies encephalitis

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Authors: Abbas Sheikhtaheri, Nasim Hashemi

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Health information systems have great benefits for clinical and managerial processes of health care organizations. However, identifying and removing constraints and barriers of implementing and using health information systems before any implementation is essential. Physicians are one of the main users of health information systems, therefore, identifying the causes of their resistance and concerns about the barriers of the implementation of these systems is very important. So the purpose of this study was to determine the barriers of the development and implementation of health information systems in terms of the Iranian physicians’ perspectives. In this study conducted in 8 selected hospitals affiliated to Tehran and Iran Universities of Medical Sciences, Tehran, Iran in 2014, physicians (GPs, residents, interns, specialists) in these hospitals were surveyed. In order to collect data, a research made questionnaire was used (Cronbach’s α = 0.95). The instrument included 25 about organizational (9), personal (4), moral and legal (3) and technical barriers (9). Participants were asked to answer the questions using 5 point scale Likert (completely disagree=1 to completely agree=5). By using a simple random sampling method, 200 physicians (from 600) were invited to study that eventually 163 questionnaires were returned. We used mean score and t-test and ANOVA to analyze the data using SPSS software version 17. 52.1% of respondents were female. The mean age was 30.18 ± 7.29. The work experience years for most of them were between 1 to 5 years (80.4 percent). The most important barriers were organizational ones (3.4 ± 0.89), followed by ethical (3.18 ± 0.98), technical (3.06 ± 0.8) and personal (3.04 ± 1.2). Lack of easy access to a fast Internet (3.67±1.91) and the lack of exchanging information (3.61±1.2) were the most important technical barriers. Among organizational barriers, the lack of efficient planning for the development and implementation systems (3.56±1.32) and was the most important ones. Lack of awareness and knowledge of health care providers about the health information systems features (3.33±1.28) and the lack of physician participation in planning phase (3.27±1.2) as well as concerns regarding the security and confidentiality of health information (3.15 ± 1.31) were the most important personal and ethical barriers, respectively. Women (P = 0.02) and those with less experience (P = 0.002) were more concerned about personal barriers. GPs also were more concerned about technical barriers (P = 0.02). According to the study, technical and ethics barriers were considered as the most important barriers however, lack of awareness in target population is also considered as one of the main barriers. Ignoring issues such as personal and ethical barriers, even if the necessary infrastructure and technical requirements were provided, may result in failure. Therefore, along with the creating infrastructure and resolving organizational barriers, special attention to education and awareness of physicians and providing solution for ethics concerns are necessary.

Keywords: barriers, development health information systems, implementation, physicians

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Authors: Akterono Budiyati, Gita Kusumo, Teguh Putra, Fritzie Rexana, Antonius Kurniawan, Aru Sudoyo, Ahmad Utomo, Andi Utama

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The presence of the programmed death ligand-1 (PD-L1) has been used in multiple clinical trials and approved as biomarker for selecting patients more likely to respond to immune checkpoint inhibitors. However, the expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence. Positive PD-L1 within tumors may result from two mechanisms, induced PD-L1 expression by T-cell presence or genetic mechanism that lead to constitutive PD-L1 expression. Amplification of PD-L1 genes was found as one of genetic mechanism which causes an increase in PD-L1 expression. In case of colorectal cancer (CRC), targeting immune checkpoint inhibitor has been recommended for patients with microsatellite instable (MSI). Although the correlation between PD-L1 expression and MSI status has been widely studied, so far the precise mechanism of PD-L1 gene activation in CRC patients, particularly in MSI population have yet to be clarified. In this present study we have profiled 61 archived formalin fixed paraffin embedded CRC specimens of patients from Medistra Hospital, Jakarta admitted in 2010 - 2016. Immunohistochemistry was performed to measure expression of PD-L1 in tumor cells as well as MSI status using antibodies against PD-L1 and MMR (MLH1, MSH2, PMS2 and MSH6), respectively. PD-L1 expression was measured on tumor cells with cut off of 1% whereas loss of nuclear MMR protein expressions in tumor cells but not in normal or stromal cells indicated presence of MSI. Subset of PD-L1 positive patients was then assessed for copy number variations (CNVs) using single Tube TaqMan Copy Number Assays Gene CD247PD-L1. We also observed KRAS mutation to profile possible genetic mechanism leading to the presence or absence of PD-L1 expression. Analysis of 61 CRC patients revealed 15 patients (24%) expressed PD-L1 on their tumor cell membranes. The prevalence of surface membrane PD-L1 was significantly higher in patients with MSI (87%; 7/8) compared to patients with microsatellite stable (MSS) (15%; 8/53) (P=0.001). Although amplification of PD-L1 gene was not found among PD-L1 positive patients, low-level amplification of PD-L1 gene was commonly observed in MSS patients (75%; 6/8) than in MSI patients (43%; 3/7). Additionally, we found 26% of CRC patients harbored KRAS mutations (16/61), so far the distribution of KRAS status did not correlate with PD-L1 expression. Our data suggest genetic mechanism through amplification of PD-L1 seems not to be the mechanism underlying upregulation of PD-L1 expression in CRC patients. However, further studies are warranted to confirm the results.

Keywords: colorectal cancer, gene amplification, microsatellite instable, programmed death ligand-1

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Authors: Varsha Salian, Shama Rao, N. Narendra, B. Mohana Kumar

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Evolving evidence proposes the existence of a highly tumorigenic subpopulation of undifferentiated, self-renewing cancer stem cells, responsible for exhibiting resistance to conventional anti-cancer therapy, recurrence, metastasis and heterogeneous tumor formation. Importantly, the mechanisms exploited by cancer stem cells to resist chemotherapy are very less understood. Oral squamous cell carcinoma (OSCC) is one of the most regularly diagnosed cancer types in India and is associated commonly with alcohol and tobacco use. Therefore, the isolation and in vitro characterization of cancer stem-like cells from patients with OSCC is a critical step to advance the understanding of the chemoresistance processes and for designing therapeutic strategies. With this, the present study aimed to establish and characterize cancer stem-like cells in vitro from OSCC. The primary cultures of cancer stem-like cell lines were established from the tissue biopsies of patients with clinical evidence of an ulceroproliferative lesion and histopathological confirmation of OSCC. The viability of cells assessed by trypan blue exclusion assay showed more than 95% at passage 1 (P1), P2 and P3. Replication rate was performed by plating cells in 12-well plate and counting them at various time points of culture. Cells had a more marked proliferative activity and the average doubling time was less than 20 hrs. After being cultured for 10 to 14 days, cancer stem-like cells gradually aggregated and formed sphere-like bodies. More spheroid bodies were observed when cultured in DMEM/F-12 under low serum conditions. Interestingly, cells with higher proliferative activity had a tendency to form more sphere-like bodies. Expression of specific markers, including membrane proteins or cell enzymes, such as CD24, CD29, CD44, CD133, and aldehyde dehydrogenase 1 (ALDH1) is being explored for further characterization of cancer stem-like cells. To summarize the findings, the establishment of OSCC derived cancer stem-like cells may provide scope for better understanding the cause for recurrence and metastasis in oral epithelial malignancies. Particularly, identification and characterization studies on cancer stem-like cells in Indian population seem to be lacking thus provoking the need for such studies in a population where alcohol consumption and tobacco chewing are major risk habits.

Keywords: cancer stem-like cells, characterization, in vitro, oral squamous cell carcinoma

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Authors: Suehyun Cho, Darrell Harrington, Florent Cros, Olin Palmer, John Caputo, Michael Kardosh, Eran Oren, William Loudon, Alex Kiselyov, Michael Shpigelmacher

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The Dandy-Walker malformation (DWM) represents a clinical syndrome manifesting as a combination of posterior fossa cyst, hypoplasia of the cerebellar vermis, and obstructive hydrocephalus. Anatomic hallmarks include hypoplasia of the cerebellar vermis, enlargement of the posterior fossa, and cystic dilatation of the fourth ventricle. Current treatments of DWM, including shunting of the cerebral spinal fluid ventricular system and endoscopic third ventriculostomy (ETV), are frequently clinically insufficient, require additional surgical interventions, and carry risks of infections and neurological deficits. Bionaut Labs develops an alternative way to treat Dandy-Walker Malformation (DWM) associated with non-communicating hydrocephalus. We utilize our discreet microsurgical Bionaut™ particles that are controlled externally and remotely to perform safe, accurate, effective fenestration of the Dandy-Walker cyst, specifically in the posterior fossa of the brain, to directly normalize intracranial pressure. Bionaut™ allows for complex non-linear trajectories not feasible by any conventional surgical techniques. The microsurgical particle safely reaches targets in the lower occipital section of the brain. Bionaut™ offers a minimally invasive surgical alternative to highly involved posterior craniotomy or shunts via direct fenestration of the fourth ventricular cyst at the locus defined by the individual anatomy. Our approach offers significant advantages over the current standards of care in patients exhibiting anatomical challenge(s) as a manifestation of DWM, and therefore, is intended to replace conventional therapeutic strategies. Current progress, including platform optimization, Bionaut™ control, and real-time imaging and in vivo safety studies of the Bionauts™ in large animals, specifically the spine and the brain of ovine models, will be discussed.

Keywords: Bionaut™, cerebral spinal fluid, CSF, cyst, Dandy-Walker, fenestration, hydrocephalus, micro-robot

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Authors: Umamaheswari Shanmugam, Silvia Ronchi, Radu Vornicu

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Software, artificial intelligence, and machine learning can improve healthcare through innovative and advanced technologies that are able to use the large amount and variety of data generated during healthcare services every day. As we read the news, over 500 machine learning or other artificial intelligence medical devices have now received FDA clearance or approval, the first ones even preceding the year 2000. One of the big advantages of these new technologies is the ability to get experience and knowledge from real-world use and to continuously improve their performance. Healthcare systems and institutions can have a great benefit because the use of advanced technologies improves the same time efficiency and efficacy of healthcare. Software-defined as a medical device, is stand-alone software that is intended to be used for patients for one or more of these specific medical intended uses: - diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of a disease, any other health conditions, replacing or modifying any part of a physiological or pathological process–manage the received information from in vitro specimens derived from the human samples (body) and without principal main action of its principal intended use by pharmacological, immunological or metabolic definition. Software qualified as medical devices must comply with the general safety and performance requirements applicable to medical devices. These requirements are necessary to ensure high performance and quality and also to protect patients’ safety. The evolution and the continuous improvement of software used in healthcare must take into consideration the increase in regulatory requirements, which are becoming more complex in each market. The gap between these advanced technologies and the new regulations is the biggest challenge for medical device manufacturers. Regulatory requirements can be considered a market barrier, as they can delay or obstacle the device approval, but they are necessary to ensure performance, quality, and safety, and at the same time, they can be a business opportunity if the manufacturer is able to define in advance the appropriate regulatory strategy. The abstract will provide an overview of the current regulatory framework, the evolution of the international requirements, and the standards applicable to medical device software in the potential market all over the world.

Keywords: artificial intelligence, machine learning, SaMD, regulatory, clinical evaluation, classification, international requirements, MDR, 510k, PMA, IMDRF, cyber security, health care systems.

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Authors: Harold M. Carag, April Charmaine D. Camacho, Girlie Nora A. Abrigo, Florencia G. Palis, Ma. Larissa Lelu P. Gata

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A technology impact assessment on the use of microbial inoculants in the reforestation and rehabilitation of forest ancestral lands of the Magbukün Aytas in Morong, Bataan was conducted. This two-year rainforestation technology aimed to determine the optimum condition for the improvement of seedling survival rate in the nursery and in the field to hasten the process of forest regeneration of Magbukün Ayta’s ancestral land. A combination of qualitative methods (key informant interviews, focus groups and participant observation), participated by the farmers who were directly involved in the project, community men and women, the council of elders and the project staff, was employed to complete this impact assessment. The recorded data were transcribed, and the accounts were broadly categorized on the following aspects: social (gender, institutional, anthropological), economic and environmental. The Australian Center for International Agricultural Research (ACIAR) framework was primarily used for the impact analysis while the Harvard Analytical Framework was specifically used for the gender impact analysis. Through this technology, a wildling nursery with more than one thousand seedlings was successfully established and served as a good area for the healthy growth of seedlings that would be planted in the forest. Results showed that this technology affected positively and negatively the various gender roles present in the community although household work remained to be the women’s responsibility. The technology introduced directly added up to the workload done by the men and women (preparing and applying fertilizer, making pots etc.) but this, in turn, provided ways to increase their sources of livelihood. The gender roles that were already present were further strengthened after the project and men remained to be in control. The technology or project in turn also benefited from the already present roles since they no longer have to assign things to them, the execution of the various roles was smoothly executed. In the anthropological aspect, their assigned task to manage the nursery was an easy responsibility because of their deep connection to the environment and their fear and beliefs on ‘engkato’ and ‘anito’ was helpful in guarding the forest. As the cultural value of these trees increases, their mindset of safeguarding the forest also heightens. Meanwhile, the welfare of the whole tribe is the ultimate determinant of the swift entry of projects. The past institutions brought ephemeral reliefs on the subsistence of the Magbukün Aytas. These were good ‘conditioning’ factors for the adoption of the technology of the project. As an attempt to turn away from the dependent of harmful chemical, the project’s way of introducing organic inputs was slowly gaining popularity in the community. Economically, the project was able to provide additional income to the farmers. However, the slow mode of payment dismayed other farmers and abandoned their roles. Lastly, major environmental effects weren’t that much observed after the application of the technology. The minor effects concentrated more on the improved conditions of the soil and water in the community. Because of the introduced technology, soil conditions became more favorable specifically for the species that were planted. The organic fertilizers used were in turn not harmful for the residents living in Sitio Kanawan. There were no human diseases caused by the technology. The conservation of the biodiversity of the forest is clearly the most evident long-term result of the project.

Keywords: ancestral lands, impact assessment, microbial inculants, reforestation

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Authors: Camila Lemos Pinto, Juliana Alves Carneiro, Patrícia Borges Botelho, João Felipe Mota

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Sarcopenia, a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, currently affects over 50 million people and increases the risk of adverse outcomes such as physical disability, poor quality of life and death. The aim of this study was to examine the efficacy of creatine supplementation associated with resistance training on muscle mass in the elderly. A 12-week, double blind, randomized, parallel group, placebo controlled trial was conducted. Participants were randomly allocated into one of the following groups: placebo with resistance training (PL+RT, n=14) and creatine supplementation with resistance training (CR + RT, n=13). The subjects from CR+RT group received 5 g/day of creatine monohydrate and the subjects from the PL+RT group were given the same dose of maltodextrin. Participants were instructed to ingest the supplement on non-training days immediately after lunch and on training days immediately after resistance training sessions dissolved in a beverage comprising 100 g of maltodextrin lemon flavored. Participants of both groups undertook a supervised exercise training program for 12 weeks (3 times per week). The subjects were assessed at baseline and after 12 weeks. The primary outcome was muscle mass, assessed by dual energy X-ray absorptiometry (DXA). The secondary outcome included diagnose participants with one of the three stages of sarcopenia (presarcopenia, sarcopenia and severe sarcopenia) by skeletal muscle mass index (SMI), handgrip strength and gait speed. CR+RT group had a significant increase in SMI and muscle (p<0.0001), a significant decrease in android and gynoid fat (p = 0.028 and p=0.035, respectively) and a tendency of decreasing in body fat (p=0.053) after the intervention. PL+RT only had a significant increase in SMI (p=0.007). The main finding of this clinical trial indicated that creatine supplementation combined with resistance training was capable of increasing muscle mass in our elderly cohort (p=0.02). In addition, the number of subjects diagnosed with one of the three stages of sarcopenia at baseline decreased in the creatine supplemented group in comparison with the placebo group (CR+RT, n=-3; PL+RT, n=0). In summary, 12 weeks of creatine supplementation associated with resistance training resulted in increases in muscle mass. This is the first research with elderly of both sexes that show the same increase in muscle mass with a minor quantity of creatine supplementation in a short period. Future long-term research should investigate the effects of these interventions in sarcopenic elderly.

Keywords: creatine, dietetic supplement, elderly, resistance training

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Authors: May Fadheel Estephan, Richard Perks

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Context: Cancer is a serious health concern that affects millions of people worldwide. Early detection and treatment are essential for improving patient outcomes. However, current methods for cancer detection have limitations, such as low sensitivity and specificity. Research Aim: The aim of this study was to develop an optical sensor for cancer detection using elastic light scattering spectroscopy (ELSS). ELSS is a noninvasive optical technique that can be used to characterize the size and concentration of particles in a solution. Methodology: An optical probe was fabricated with a 100-μm-diameter core and a 132-μm centre-to-centre separation. The probe was used to measure the ELSS spectra of polystyrene spheres with diameters of 2, 0.8, and 0.413 μm. The spectra were then analysed to determine the size and concentration of the spheres. Findings: The results showed that the optical probe was able to differentiate between the three different sizes of polystyrene spheres. The probe was also able to detect the presence of polystyrene spheres in suspension concentrations as low as 0.01%. Theoretical Importance: The results of this study demonstrate the potential of ELSS for cancer detection. ELSS is a noninvasive technique that can be used to characterize the size and concentration of cells in a tissue sample. This information can be used to identify cancer cells and assess the stage of the disease. Data Collection: The data for this study were collected by measuring the ELSS spectra of polystyrene spheres with different diameters. The spectra were collected using a spectrometer and a computer. Analysis Procedures: The ELSS spectra were analysed using a software program to determine the size and concentration of the spheres. The software program used a mathematical algorithm to fit the spectra to a theoretical model. Question Addressed: The question addressed by this study was whether ELSS could be used to detect cancer cells. The results of the study showed that ELSS could be used to differentiate between different sizes of cells, suggesting that it could be used to detect cancer cells. Conclusion: The findings of this research show the utility of ELSS in the early identification of cancer. ELSS is a noninvasive method for characterizing the number and size of cells in a tissue sample. To determine cancer cells and determine the disease's stage, this information can be employed. Further research is needed to evaluate the clinical performance of ELSS for cancer detection.

Keywords: elastic light scattering spectroscopy, polystyrene spheres in suspension, optical probe, fibre optics

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Authors: Albert Amagyei, Julia Carroll, Amanda R. Amorim Adegboye, Laura Strumidlo, Rosie Kneafsey

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Introduction: Classroom-based learning has persisted as the mainstream model of pre-registration nurse education. This model is often rigid, teacher-centered, and unable to support active learning and the practical learning needs of nursing students. Health Education England (HEE), a public body of the Department of Health and Social Care, hypothesises that blended learning (BL) programmes may address health system and nursing profession challenges, such as nursing shortages and lack of digital expertise, by exploring opportunities for providing predominantly online, remote-access study which may increase nursing student recruitment, offering alternate pathways to nursing other than the traditional classroom route. This study will provide evidence for blended learning strategies adopted in nursing education as well as examine nursing student learning experiences concerning the challenges and opportunities related to using blended learning within nursing education. Objective: This review will explore the challenges and opportunities of BL within pre-registration nurse education from the student's perspective. Methods: The search was completed within five databases. Eligible studies were appraised independently by four reviewers. The JBI-convergent segregated approach for mixed methods review was used to assess and synthesize the data. The study’s protocol has been registered with the International Register of Systematic Reviews with registration number// PROSPERO (CRD42023423532). Results: Twenty-seven (27) studies (21 quantitative and 6 qualitative) were included in the review. The study confirmed that BL positively impacts nursing students' learning outcomes, as demonstrated by the findings of the meta-analysis and meta-synthesis. Conclusion: The review compared BL to traditional learning, simulation, laboratory, and online learning on nursing students’ learning and programme outcomes as well as learning behaviour and experience. The results show that BL could effectively improve nursing students’ knowledge, academic achievement, critical skills, and clinical performance as well as enhance learner satisfaction and programme retention. The review findings outline that students’ background characteristics, BL design, and format significantly impact the success of the BL nursing programme.

Keywords: nursing student, blended learning, pre-registration nurse education, online learning

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Authors: Temesgen Sidamo, Prakruti S. Rao, Eleni Akllilu, Workineh Shibeshi, Yumi Park, Yong-Soon Cho, Jae-Gook Shin, Scott K. Heysell, Stellah G. Mpagama, Ephrem Engidawork

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The fluoroquinolones (FQs) are used off-label for the treatment of multidrug-resistant tuberculosis (MDR-TB), and for evaluation in shortening the duration of drug-susceptible TB in recently prioritized regimens. Within the class, levofloxacin (LFX) and moxifloxacin (MXF) play a substantial role in ensuring success in treatment outcomes. However, sub-therapeutic plasma concentrations of either LFX or MXF may drive unfavorable treatment outcomes. To the best of our knowledge, the pharmacokinetics of LFX and MXF in Ethiopian patients with MDR-TB have not yet been investigated. Therefore, the aim of this study was to develop a population pharmacokinetic (PopPK) model of levofloxacin (LFX) and moxifloxacin (MXF) and assess the percent probability of target attainment (PTA) as defined by the ratio of the area under the plasma concentration-time curve over 24-h (AUC0-24) and the in vitro minimum inhibitory concentration (MIC) (AUC0-24/MIC) in Ethiopian MDR-TB patients. Steady-state plasma was collected from 39 MDR-TB patients enrolled in the programmatic treatment course and the drug concentrations were determined using optimized liquid chromatography-tandem mass spectrometry. In addition, the in vitro MIC of the patients' pretreatment clinical isolates was determined. PopPK and simulations were run at various doses, and PK parameters were estimated. The effect of covariates on the PK parameters and the PTA for maximum mycobacterial kill and resistance prevention was also investigated. LFX and MXF both fit in a one-compartment model with adjustments. The apparent volume of distribution (V) and clearance (CL) of LFX were influenced by serum creatinine (Scr), whereas the absorption constant (Ka) and V of MXF were influenced by Scr and BMI, respectively. The PTA for LFX maximal mycobacterial kill at the critical MIC of 0.5 mg/L was 29%, 62%, and 95% with the simulated 750 mg, 1000 mg, and 1500 mg doses, respectively, whereas the PTA for resistance prevention at 1500 mg was only 4.8%, with none of the lower doses achieving this target. At the critical MIC of 0.25 mg/L, there was no difference in the PTA (94.4%) for maximum bacterial kill among the simulated doses of MXF (600 mg, 800 mg, and 1000 mg), but the PTA for resistance prevention improved proportionately with dose. Standard LFX and MXF doses may not provide adequate drug exposure. LFX PopPK is more predictable for maximum mycobacterial kill, whereas MXF's resistance prevention target increases with dose. Scr and BMI are likely to be important covariates in dose optimization or therapeutic drug monitoring (TDM) studies in Ethiopian patients.

Keywords: population PK, PTA, moxifloxacin, levofloxacin, MDR-TB patients, ethiopia

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Authors: Joulié Aurélien, Jourdain Elsa, Bailly Xavier, Gasqui Patrick, Yang Elise, Leblond Agnès, Rousset Elodie, Sidi-Boumedine Karim

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Q fever is a worldwide zoonosis caused by the gram-negative obligate intracellular bacterium Coxiella burnetii. Following the recent outbreaks in the Netherlands, a hyper virulent clone was found to be the cause of severe human cases of Q fever. In livestock, Q fever clinical manifestations are mainly abortions. Although the abortion rates differ between ruminant species, C. burnetii’s virulence remains understudied, especially in enzootic areas. In this study, the infectious potential of three C. burnetii isolates collected from French farms of small ruminants were compared to the reference strain Nine Mile (in phase II and in an intermediate phase) using an in vivo (CD1 mice) model. Mice were challenged with 105 live bacteria discriminated by propidium monoazide-qPCR targeting the icd-gene. After footpad inoculation, spleen and popliteal lymph node were harvested at 10 days post-inoculation (p.i). The strain invasiveness in spleen and popliteal nodes was assessed by qPCR assays targeting the icd-gene. Preliminary results showed that the avirulent strains (in phase 2) failed to pass the popliteal barrier and then to colonize the spleen. This model allowed a significant differentiation between strain’s invasiveness on biological host and therefore identifying distinct virulence profiles. In view of these results, we plan to go further by testing fifteen additional C. burnetii isolates from French farms of sheep, goat and cattle by using the above-mentioned in vivo model. All 15 strains display distant MLVA (multiple-locus variable-number of tandem repeat analysis) genotypic profiles. Five of the fifteen isolates will bee also tested in vitro on ovine and bovine macrophage cells. Cells and supernatants will be harvested at day1, day2, day3 and day6 p.i to assess in vitro multiplication kinetics of strains. In conclusion, our findings might help the implementation of surveillance of virulent strains and ultimately allow adapting prophylaxis measures in livestock farms.

Keywords: Q fever, invasiveness, ruminant, virulence

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Authors: Muhammad Shafi'u Adamu

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This study examined the effects of two Group Cognitive Behavioural Therapies (Cognitive Restructuring and Rational Emotive Behavioural Therapy) on Psychological Distress of awaiting-trial Inmates in Correctional Centres in North-West, Nigeria. The study had four specific objectives, four research questions, and four null hypotheses. The study used a quasi-experimental design that involved pre-test and post-test. The population comprised of all 7,962 awaiting-trial inmates in correctional centres in North-west, Nigeria. 131 awaiting trial inmates from three intact Correctional Centres were randomly selected using the census technique. The respondents were sampled and randomly put into 3 groups (CR, REBT and Control). Kessler Psychological Distress Scale (K10) was adapted for data collection in the study. The instrument was validated by experts and subjected to pilot study using Cronbach's Alpha with reliability co-efficient of 0.772. Each group received treatment for 8 consecutive weeks (60 minutes/week). Data collected from the field were subjected to descriptive statistics of mean, standard deviation and mean difference to answer the research questions. Inferential statistics of ANOVA and independent sample t-test were used to test the null hypotheses at P≤ 0.05 level of significance. Results in the study revealed that there was no significant difference among the pre-treatment mean scores of experimental and control groups. Statistical evidence also showed a significant difference among the mean sores of the three groups, and thus, results of the Post Hoc multiple-comparison test indicating the posttreatment reduction of psychological distress on the awaiting-trial inmates. Documented output also showed a significant difference between the post-treatment psychologically distressed mean scores of male and female awaiting-trial inmates, but there was no difference on those exposed to REBT. The research recommends that a standardized structured CBT counselling technique treatment should be designed for correctional centres across Nigeria, and CBT counselling techniques could be used in the treatment of PD in both correctional and clinical settings.

Keywords: awaiting-trial inmates, cognitive restructuring, correctional centres, group cognitive behavioural therapies, rational emotive behavioural therapy

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Authors: Anderson Rocha-Buelvas, Jaqueline Mena Huertas, Edith Burbano Rosero, Arsenio Hidalgo Troya, Mauricio Casas Cruz

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COVID-19 is a disruptive pandemic for the public health and economic system of whole countries, including Colombia. Nariño Department is the southwest of the country and draws attention to being on the border with Ecuador, constantly facing demographic transition affecting infections between countries. In Nariño, the early routine diagnosis of SARS-CoV-2, which can be handled at BSL-2, has affected the transmission dynamics of COVID-19. However, new emerging and re-emerging viruses with biological flexibility classified as a Risk Group 3 agent can take advantage of epidemiological opportunities, generating the need to increase clinical diagnosis, mainly in border regions between countries. The overall objective of this project was to assure the quality of the analytical process in the diagnosis of high biological risk pathogens in Nariño by building a laboratory that includes biosafety level (BSL)-2 and (BSL)-3 containment zones. The delimitation of zones was carried out according to the Verification Tool of the National Health Institute of Colombia and following the standard requirements for the competence of testing and calibration laboratories of the International Organization for Standardization. This is achieved by harmonization of methods and equipment for effective and durable diagnostics of the large-scale spread of highly pathogenic microorganisms, employing negative-pressure containment systems and UV Systems in accordance with a finely controlled electrical system and PCR systems as new diagnostic tools. That increases laboratory capacity. Protection in BSL-3 zones will separate the handling of potentially infectious aerosols within the laboratory from the community and the environment. It will also allow the handling and inactivation of samples with suspected pathogens and the extraction of molecular material from them, allowing research with pathogens with high risks, such as SARS-CoV-2, Influenza, and syncytial virus, and malaria, among others. The diagnosis of these pathogens will be articulated across the spectrum of basic, applied, and translational research that could receive about 60 daily samples. It is expected that this project will be articulated with the health policies of neighboring countries to increase research capacity.

Keywords: medical laboratory science, SARS-CoV-2, public health surveillance, Colombia

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Authors: Peter Edwar Mortada Nasif

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The use of CAD (Computer Aided Design) technology is ubiquitous in the architecture, engineering and construction (AEC) industry. This has led to its inclusion in the curriculum of architecture schools in Nigeria as an important part of the training module. This article examines the ethical issues involved in implementing CAD (Computer Aided Design) content into the architectural education curriculum. Using existing literature, this study begins with the benefits of integrating CAD into architectural education and the responsibilities of different stakeholders in the implementation process. It also examines issues related to the negative use of information technology and the perceived negative impact of CAD use on design creativity. Using a survey method, data from the architecture department of Chukwuemeka Odumegwu Ojukwu Uli University was collected to serve as a case study on how the issues raised were being addressed. The article draws conclusions on what ensures successful ethical implementation. Millions of people around the world suffer from hepatitis C, one of the world's deadliest diseases. Interferon (IFN) is treatment options for patients with hepatitis C, but these treatments have their side effects. Our research focused on developing an oral small molecule drug that targets hepatitis C virus (HCV) proteins and has fewer side effects. Our current study aims to develop a drug based on a small molecule antiviral drug specific for the hepatitis C virus (HCV). Drug development using laboratory experiments is not only expensive, but also time-consuming to conduct these experiments. Instead, in this in silicon study, we used computational techniques to propose a specific antiviral drug for the protein domains of found in the hepatitis C virus. This study used homology modeling and abs initio modeling to generate the 3D structure of the proteins, then identifying pockets in the proteins. Acceptable lagans for pocket drugs have been developed using the de novo drug design method. Pocket geometry is taken into account when designing ligands. Among the various lagans generated, a new specific for each of the HCV protein domains has been proposed.

Keywords: drug design, anti-viral drug, in-silicon drug design, hepatitis C virus, computer aided design, CAD education, education improvement, small-size contractor automatic pharmacy, PLC, control system, management system, communication

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Authors: Alexander Zotov, Ilkin Osmanov, Emil Sakharov, Oleg Shelest, Aleksander Troitskiy, Robert Khabazov

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Objective: Thoracoscopic surgical ablation of atrial fibrillation (AF) includes two technologies in performing of operation. 1st strategy used is the AtriCure device (bipolar, nonirrigated, non clamping), 2nd strategy is- the Medtronic device (bipolar, irrigated, clamping). The study presents a comparative analysis of clinical outcomes of two strategies in thoracoscopic ablation of AF using AtriCure vs. Medtronic devices. Methods: In 2 center study, 123 patients underwent thoracoscopic ablation of AF for the period from 2016 to 2020. Patients were divided into two groups. The first group is represented by patients who applied the AtriCure device (N=63), and the second group is - the Medtronic device (N=60), respectively. Patients were comparable in age, gender, and initial severity of the condition. Among the patients, in group 1 were 65% males with a median age of 57 years, while in group 2 – 75% and 60 years, respectively. Group 1 included patients with paroxysmal form -14,3%, persistent form - 68,3%, long-standing persistent form – 17,5%, group 2 – 13,3%, 13,3% and 73,3% respectively. Median ejection fraction and indexed left atrial volume amounted in group 1 – 63% and 40,6 ml/m2, in group 2 - 56% and 40,5 ml/m2. In addition, group 1 consisted of 39,7% patients with chronic heart failure (NYHA Class II) and 4,8% with chronic heart failure (NYHA Class III), when in group 2 – 45% and 6,7%, respectively. Follow-up consisted of laboratory tests, chest Х-ray, ECG, 24-hour Holter monitor, and cardiopulmonary exercise test. Duration of freedom from AF, distant mortality rate, and prevalence of cerebrovascular events were compared between the two groups. Results: Exit block was achieved in all patients. According to the Clavien-Dindo classification of surgical complications fraction of adverse events was 14,3% and 16,7% (1st group and 2nd group, respectively). Mean follow-up period in the 1st group was 50,4 (31,8; 64,8) months, in 2nd group - 30,5 (14,1; 37,5) months (P=0,0001). In group 1 - total freedom of AF was in 73,3% of patients, among which 25% had additional antiarrhythmic drugs (AADs) therapy or catheter ablation (CA), in group 2 – 90% and 18,3%, respectively (for total freedom of AF P<0,02). At follow-up, the distant mortality rate in the 1st group was – 4,8%, and in the 2nd – no fatal events. Prevalence of cerebrovascular events was higher in the 1st group than in the 2nd (6,7% vs. 1,7% respectively). Conclusions: Despite the relatively shorter follow-up of the 2nd group in the study, applying the strategy using the Medtronic device showed quite encouraging results. Further research is needed to evaluate the effectiveness of this strategy in the long-term period.

Keywords: atrial fibrillation, clamping, ablation, thoracoscopic surgery

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Authors: Geliashvili T. M., Tyulyandina A. S., Valiev A. K., Kononets P. V., Kharatishvili T. K., Salkov A. G., Pronin A. I., Gadzhieva E. H., Parnas A. V., Ilyakov V. S.

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Aim/Introduction: Metastasis (Mts) to the sternum, while extremely rare in differentiated thyroid cancer (DTC) (1), requires a personalized, multidisciplinary treatment approach. In aggressively growing Mts to the sternum, which rapidly become unresectable, a comprehensive therapeutic and diagnostic approach is particularly important. Materials and methods: We present a clinical case of solitary Mts to the sternum as first manifestation of a papillary thyroid microcarcinoma in a 55-year-old man. Results: 18F-FDG PET/CT after thyroidectomy confirmed the solitary Mts to the sternum with extremely high FDG uptake (SUVmax=71,1), which predicted its radioiodine-refractory (RIR). Due to close attachment to the mediastinum and rapid growth, Mts was considered unresectable. During the next three months, the patient received targeted therapy with the tyrosine kinase inhibitor (TKI) Lenvatinib 24 mg per day. 1st course of radioiodine therapy (RIT) 6 GBq was also performed, the results of which confirmed the RIR of the tumor process. As a result of systemic therapy (targeted therapy combined with RIT and suppressive hormone therapy with L-thyroxine), there was a significant biochemical response (decrease of serum thyroglobulin level from 50,000 ng/ml to 550 ng/ml) and a partial response with decrease of tumor size (from 80x69x123 mm to 65x50x112 mm) and decrease of FDG accumulation (SUVmax from 71.1 to 63). All of this made possible to perform surgical treatment of Mts - sternal extirpation with its replacement by an individual titanium implant. At the control examination, the stimulated thyroglobulin level was only 134 ng/ml, and PET/CT revealed postoperative areas of 18F-FDG metabolism in the removed sternal Mts. Also, 18F-FDG PET/CT in the early (metabolic) stage revealed two new bone Mts (in the area of L3 SUVmax=17,32 and right iliac bone SUVmax=13,73), which, as well as the removed sternal Mts, appeared to be RIRs at the 2nd course of RIT 6 GBq. Subsequently, on 02.2022, external beam radiation therapy (EBRT) was performed on the newly identified oligometastatic bone foci. At present, the patient is under dynamic monitoring and in the process of suppressive hormone therapy with L-thyroxine. Conclusion: Thus, only due to the early prescription of targeted TKI therapy was it possible to perform surgical resection of Mts to the sternum, thereby improve the patient's quality of life and preserve the possibility of radical treatment in case of oligometastatic disease progression.

Keywords: differentiated thyroid cancer, metastasis to the sternum, radioiodine therapy, radioiodine-refractory cancer, targeted therapy, lenvatinib

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Authors: Lee Rui, Rajeev Ramachandran

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The approach to recurrent fevers in the paediatric or adolescent age group is not a straightforward one. Causes range from infectious diseases to rheumatological conditions to endocrinopathies, and are usually accompanied by weight loss rather than weight gain. We present an interesting case of a 16-year-old girl brought by her mother to the General Pediatrics Clinic for concerns of recurrent fever paired with significant weight gain over 1.5 years, with no identifiable cause found despite extensive work-up by specialists ranging from Rheumatologists to Oncologists. This case provides a learning opportunity on the approach to weight gain paired with persistent fevers in a paediatric population, one which is not commonly encountered and prompts further evaluation and consideration of less common diagnoses. In a span of 2 years, the girl’s weight had increased from 55 kg at 13 years old (75th centile) to 73.9 kg at 16 years old (>97th centile). About 1 year into her rapid weight gain, she started developing recurrent fevers of documented temperatures > 37.5 – 38.6 every 2-3 days, resulting in school absenteeism when she was sent home after temperature-taking in school found her to be febrile. The rapid onset of weight gain paired with unexplained fevers prompted the treating physician to consider the diagnosis of ROHHAD syndrome. Rapid onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) syndrome is a rare disorder first described in 2007. It is characterized by dysfunction of the autonomic and endocrine system, characterized by hyperphagia and rapid-onset weight gain. This rapid weight gain is classically followed by hypothalamic manifestations with neuroendocrine deficiencies, hypo-ventilatory breathing abnormalities, and autonomic dysregulation. ROHHAD is challenging to diagnose with and diagnosis is made based mostly on clinical judgement. However if truly diagnosed, the condition is characterized by high morbidity and mortality rates. Early recognition of sleep disorders breathing and targeted therapeutic interventions helps limit morbidity and mortality associated with ROHHAD syndrome. This case poses an interesting diagnostic challenge and a diagnosis of ROHHAD has to be considered, given the serious complications that can come with disease progression while conditions such as Munchausen’s or drug fever remain as diagnoses of exclusion until we have exhausted all other possible conditions.

Keywords: pediatrics, endocrine, weight gain, recurrent fever, adolescent

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Authors: Handan Alan, Ulkü Baykal

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Personal characteristics help people understand and recognize both themselves and other people. They are also known to have direct effects on managerial behaviors. Managers’ personalities indicate how they think, perceive reality and relate to others, and affect their decision-making and problem-solving methods. This descriptive study aims to determine the personal characteristics of nurse managers and the personal and professional factors that affect them since sufficient data does not exist on personal characteristics despite the focus on the leadership and managerial characteristics in nursing. The study population consisted of nurses working in administrative positions at hospitals affiliated with the public hospitals union, research and practice hospitals affiliated with universities and private hospitals in cities in the Marmara Region. The study sample consisted of nurse managers working in the hospitals that permitted conducting the study (excluding private branch hospitals). The data were collected after obtaining the approval of the Clinical Research Ethics Committee of Çanakkale Onsekiz Mart University (Approval date: 1.7.2015, Decision No: 2015-01) and written official permissions from the administrations of the hospitals included in the study. The data analysis was carried out using means and standard deviations (SD) as descriptive statistics, one-way analysis of variance for inter-group comparisons and the independent samples t-test for paired group comparisons. A significance threshold of p < 0.05 was used to evaluate the findings. The data were collected using the Five Factor Personality Inventory. The study included 900 nurse managers, who obtained the highest mean score on the conscientiousness dimension (X=4.22 ±0.35). This dimension was followed by their mean scores on the agreeableness (X=4.06±0.40), intelligence (X=4.05±0.37), extroversion (X=3.50±0.43), and emotional instability (X=2.07±0.53) dimensions. Statistically significant differences were found between the independent variables of age, gender, marital status, education level, work institution, professional experience, institutional experience, managerial experience, administrative position, work unit and managerial education when compared using the five factor personality inventory (p < 0.05). In conclusion, the nurse managers described themselves having high conscientiousness. Statistically significant differences were found between the five factor personality inventory mean scores and their personal and professional characteristics.

Keywords: nurse manager, personality, personal characteristics, professional characteristics

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Authors: Uraib Sharaha, Ahmad Salman, Eladio Rodriguez-Diaz, Elad Shufan, Klaris Riesenberg, Irving J. Bigio, Mahmoud Huleihel

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Antimicrobial drugs have an important role in controlling illness associated with infectious diseases in animals and humans. However, the increasing resistance of bacteria to a broad spectrum of commonly used antibiotics has become a global health-care problem. Rapid determination of antimicrobial susceptibility of a clinical isolate is often crucial for the optimal antimicrobial therapy of infected patients and in many cases can save lives. The conventional methods for susceptibility testing like disk diffusion are time-consuming and other method including E-test, genotyping are relatively expensive. Fourier transform infrared (FTIR) microscopy is rapid, safe, and low cost method that was widely and successfully used in different studies for the identification of various biological samples including bacteria. The new modern infrared (IR) spectrometers with high spectral resolution enable measuring unprecedented biochemical information from cells at the molecular level. Moreover, the development of new bioinformatics analyses combined with IR spectroscopy becomes a powerful technique, which enables the detection of structural changes associated with resistivity. The main goal of this study is to evaluate the potential of the FTIR microscopy in tandem with machine learning algorithms for rapid and reliable identification of bacterial susceptibility to antibiotics in time span of few minutes. The bacterial samples, which were identified at the species level by MALDI-TOF and examined for their susceptibility by the routine assay (micro-diffusion discs), are obtained from the bacteriology laboratories in Soroka University Medical Center (SUMC). These samples were examined by FTIR microscopy and analyzed by advanced statistical methods. Our results, based on 550 E.coli samples, were promising and showed that by using infrared spectroscopic technique together with multivariate analysis, it is possible to classify the tested bacteria into sensitive and resistant with success rate higher than 85% for eight different antibiotics. Based on these preliminary results, it is worthwhile to continue developing the FTIR microscopy technique as a rapid and reliable method for identification antibiotic susceptibility.

Keywords: antibiotics, E. coli, FTIR, multivariate analysis, susceptibility

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Authors: Xiaoyu Sun

Abstract:

In recent years, the rapid development of Artificial Intelligence (AI) has extensively promoted medicine, pharmaceutical, and other related fields. The medical research and development of artificial intelligence by scientific and commercial organizations are on the fast track. The ethics review is one of the critical procedures of registration to get the products approved and launched. However, the SOPs for ethics review is not enough to guide the healthy and rapid development of artificial intelligence in healthcare in China. Ethical Review Measures for Biomedical Research Involving Human Beings was enacted by the National Health Commission of the People's Republic of China (NHC) on December 1st, 2016. However, from a legislative design perspective, it was neither updated timely nor in line with the trends of AI international development. Therefore, it was great that NHC published a consultation paper on the updated version on March 16th, 2021. Based on the most updated laws and regulations in the States and EU, and in-depth-interviewed 11 subject matter experts in China, including lawmakers, regulators, and key members of ethics review committees, heads of Regulatory Affairs in SaMD industry, and data scientists, several suggestions were proposed on top of the updated version. Although the new version indicated that the Ethics Review Committees need to be created by National, Provincial and individual institute levels, the review authorities of different levels were not clarified. The suggestion is that the precise scope of review authorities for each level should be identified based on Risk Analysis and Management Model, such as the complicated leading technology, gene editing, should be reviewed by National Ethics Review Committees, it will be the job of individual institute Ethics Review Committees to review and approve the clinical study with less risk such as an innovative cream to treat acne. Furthermore, to standardize the research and development of artificial intelligence in healthcare in the age of AI, more clear guidance should be given to data security in the layers of data, algorithm, and application in the process of ethics review. In addition, transparency and responsibility, as two of six principles in the Rome Call for AI Ethics, could be further strengthened in the updated version. It is the shared goal among all countries to manage well and develop AI to benefit human beings. Learned from the other countries who have more learning and experience, China could be one of the most advanced countries in artificial intelligence in healthcare.

Keywords: biomedical research involving human beings, data security, ethics committees, ethical review, medical artificial intelligence

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Authors: Jamila Fakchich, Mostafa Jamila Lazaar Elachouri, Lakhder Fakchich, Fatna Ouali, Abd Errazzak Belkacem

Abstract:

Diabetes is a chronic metabolic disease that has a significant impact on the health, quality of life, and life expectancy of patients as well as the health care system. By its nature diabetes, is a multisystem disease with wide-ranging complication that span nearly all region of the body. This epidemic problem, however, is not unique to the industrialized society, but has also hardly struck the developing countries. In Morocco, as developing country, there is an epidemic rise in diabetes, with ensuing concern about the management and control of this disease; it began a chronic burdensome disease of largely middle-aged and elderly people, with a long course and serious complications often resulting in high death-rate, the treatment of diabetes spent vast amount of resources including medicines, diets, physical training. Treatment of this disease is considered problematic due to the lack of effective and safe drugs capable of inducing sustained clinical, biochemical, and histological cure. In Moroccan society, the phytoremedies are some times the only affordable sources of healthcare, particularly for the people in remote areas. In this paper, we present a synthesis work obtained from the ethnobotanical data reported in different specialized journals. A Synthesis of four published ethnobotanical studies that have been carried out in different region of Morocco by different team seekers during the period from 1997 to 2015. Medicinal plants inventoried by different seekers in four Moroccan’s areas have been regrouped and codified, then, Factorial Analysis (FA) and Principal Components Analysis (PCA) are used to analyse the aggregated data from the four studies and plants are classified according to their frequency of use by population. Our work deals with an attempt to gather information on some traditional uses of medicinal plants from different regions of Morocco, also, it was designed to give a set of medicinal plants commonly used by Moroccan people in the treatment of diabetes; In this paper, we intended to provide a basic knowledge about plant species used by Moroccan society for treatment of diabetes. One of the most interesting aspects of this type of works is to assess the relative cultural importance of medicinal plants for specific illnesses and exploring its usefulness in the context of diabetes.

Keywords: Morocco, medicinal plants, ethnobotanical, diabetes, phytoremedies

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