Search results for: clinical self-efficacy

Authors: Yemane Hailu Fissuh, Zhongzhan Zhang

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In biomedical researches and randomized clinical trials, the most commonly interested outcomes are time-to-event so-called survival data. The importance of robust models in this context is to compare the effect of randomly controlled experimental groups that have a sense of causality. Causal estimation is the scientific concept of comparing the pragmatic effect of treatments conditional to the given covariates rather than assessing the simple association of response and predictors. Hence, the causal effect based semiparametric transformation model was proposed to estimate the effect of treatment with the presence of possibly time-varying covariates. Due to its high flexibility and robustness, the semiparametric transformation model which shall be applied in this paper has been given much more attention for estimation of a causal effect in modeling left-truncated and right censored survival data. Despite its wide applications and popularity in estimating unknown parameters, the maximum likelihood estimation technique is quite complex and burdensome in estimating unknown parameters and unspecified transformation function in the presence of possibly time-varying covariates. Thus, to ease the complexity we proposed the modified estimating equations. After intuitive estimation procedures, the consistency and asymptotic properties of the estimators were derived and the characteristics of the estimators in the finite sample performance of the proposed model were illustrated via simulation studies and Stanford heart transplant real data example. To sum up the study, the bias of covariates was adjusted via estimating the density function for truncation variable which was also incorporated in the model as a covariate in order to relax the independence assumption of failure time and truncation time. Moreover, the expectation-maximization (EM) algorithm was described for the estimation of iterative unknown parameters and unspecified transformation function. In addition, the causal effect was derived by the ratio of the cumulative hazard function of active and passive experiments after adjusting for bias raised in the model due to the truncation variable.

Keywords: causal estimation, EM algorithm, semiparametric transformation models, time-to-event outcomes, time-varying covariate

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Authors: Wan-Ling Jiang, Hsin Chi, Jia-Lu Cheng, Ming-Fang Cheng

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Background: Investigating the risk factors for the fecal carriage of third-generation cephalosporin-resistant E.coli could contribute to further disease prevention. Previous research on third-generation cephalosporin-resistant prevalence in children in different regions of Taiwan is limited. This project aims to explore the risk factors and regional differences in the prevalence of third-generation cephalosporin-resistant and other antibiotic-resistant E. coli in the northern, southern, and eastern regions of Taiwan. Methods: We collected data from children aged 0 to 18 from community or outpatient clinics from July 2022 to May 2023 in southern, northern, and eastern Taiwan. The questionnaire was designed to survey the characteristics of participants and possible risk factors, such as clinical information, household environment, drinking water, and food habits. After collecting fecal samples and isolating stool culture with E.coli, antibiotic sensitivity tests and MLST typing were performed. Questionnaires were used to analyze the risk factors of third-generation cephalosporin-resistant E. coli in the three different regions of Taiwan. Results: In the total 246 stool samples, third-generation cephalosporin-resistant E.coli accounted for 37.4% (97/246) of all isolates. Among the three different regions of Taiwan, the highest prevalence of fecal carriage with third-generation cephalosporin-resistant E.coli was observed in southern Taiwan (42.7%), followed by northern Taiwan (35.5%) and eastern Taiwan (28.4%). Multi-drug resistant E. coli had prevalence rates of 51.9%, 66.3%, and 37.1% in the northern, southern, and eastern regions, respectively. MLST typing revealed that ST131 was the most prevalent type (11.8%). The prevalence of ST131 in northern, southern, and eastern Taiwan was 10.1%, 12.3%, and 13.2%, respectively. Risk factors analysis identified lower paternal education, overweight status, and non-vegetarian diet as statistical significance risk factors for third-generation cephalosporin-resistant E.coli. Conclusion: The fecal carriage rates of antibiotic-resistant E. coli among Taiwanese children were on the rise. This study found regional disparities in the prevalence of third-generation cephalosporin-resistant and multi-drug-resistant E. coli, with southern Taiwan having the highest prevalence. Lower paternal education, overweight, and non-vegetarian diet were the potential risk factors of third-generation cephalosporin-resistant E. coli in this study.

Keywords: Escherichia coli, fecal carriage, antimicrobial resistance, risk factors, prevalence

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Authors: Catherine Mary Abou-Zaid, Sandra Goodwin

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This study was conducted in a cardiac center in Bahrain. The rise in the amount of obese patients’ both men and women, being admitted for surgical procedures has become an issue to the nurses and doctors as these patients pose a high risk of major complications arising from their problem. The cessation of obesity in the country is very high and obesity-related diseases has been the cause of concern among men and women, also related individual diseases such as cardiovascular, diabetes and chronic respiratory diseases are rising dramatically within Bahrain in the last 10 years. Rationale for the Study: The ontological approach will help to understand and assess the true nature of the social world and how the world looks at obesity. Obesity has to be looked at as being a realistic ongoing issue. The epistemological approach will look at the theory of the origins of the nature of knowledge, set the rule of validating and learning in the social world of what can be done to curb this concept and how this can help prevent otherwise preventable diseases. Design Methodology: The qualitative design methodology took the form of an ontological/epistemological approach using phenomenology as a framework. The study was based on a social research issue, therefore, ontological ‘realism and idealism’ will feature as the nature of the world from a social and natural context. Epistemological positions of the study will be how we as researchers will find the actual social world and the limiting of that knowledge. The one-to-one interviews will be transcribed and the taped verbatim will be coded and charted giving the thematic analytic results. Recommendations: The significance of the research brought many recommendations. These recommendations were taken from the themes and sub-themes and were presented to the centers management and the necessary arrangements for updating knowledge and attitudes towards obesity in cardiac patients was then presented to the in-service education department. Workshops and training sessions on promoting health education were organized and put into the educational calendar for the next academic year. These sessions would look at patient autonomy, the patients’ rights, healthy eating for patients and families and the risks associated with obesity in cardiac disease processes.

Keywords: cardiac patients, diabetes, education & training, obesity cessation, qualitative

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Authors: Hamdy Khamis Korayem, Manal Yehia Tayel, Abeer Shawky El Hadedy, Emmanuel Kamal Aziz Saba, Shimaa Badr Abdelnaby Badr

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The aim of the current study was to demonstrate whether serum Interleukin-18 (IL-18) is increased in rheumatoid arthritis (RA) and its correlation with disease activity, functional disability and quality of life in RA patients. The study included 30 RA patients and 20 healthy normal control subjects. The RA patients were diagnosed according to the 2010 ACR/EULAR classification criteria for RA with the exclusion of those who had diabetes mellitus, endocrine disorders, associated rheumatologic diseases, viral hepatitis B or C and other diseases with increased serum IL-18 level. All patients were subjected to clinical evaluation of the musculoskeletal system. Disease activity was assessed by disease activity score 28 with 4 variables (DAS 28). Functional disability was assessed by health assessment questionnaire disability index (HAQ-DI). The quality of life was assessed by Short form-36 (SF-36) questionnaire. Radiological assessment of both hands and feet by Sharp/van der Heijde (SvH) scoring method. Laboratory parameters including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) were assessed in patients and serum level of IL-18 in both patients and control subjects. There was no statistically significant difference between patient and control group as regards age and sex. Among patients, 29 % were females and the age range was between 25 to 55 years. Extra-articular manifestations were presented in 56.7% of the patients. The mean of DAS 28 score was 5.73±1.46 and that of HAQ-DI was 1.22±0.72 while that of SF-36 was 40.03±13.96. The level of serum IL-18 was significantly higher in patients than in the control subjects (P= 0.030). Serum IL-18 was correlated with ACPA among the patient group. There were no statistically significant correlations between serum IL-18 and DAS28, HAQ-DI, SF-36, total SvH score and the other laboratory results. In conclusion, IL-18 is significantly higher in RA patient than in healthy control subjects and positively correlated with ACPA level. IL-18 is associated with extra-articular manifestations. However, it is not correlated with other laboratory parameters, disease activity, functional disability, quality of life nor radiological severity.

Keywords: disease activity score, Interleukin-18, quality of life assessment, rheumatoid arthritis

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Authors: Ishfaq A. Bukhari, Bassem Yousef Sheikh, Abdulrahman Almotrefi, Osama Yousaf, Amer Mahmood

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Olive oil is the primary source of fat in the Mediterranean diet which is associated with a low mortality for cardiovascular disease. Olive oil is rich in monounsaturated fatty acids, and has been reported for variety of beneficial cardiovascular effects including blood pressure lowering, anti-platelet, anti-diabetic and anti-inflammatory effects. Growing number evidences from preclinical and clinical studies have shown that olive oil improves insulin resistance, decrease vessels stiffness and prevent thromboembolism. We evaluated the effects of olive against streptozotocin-induced physiological disorders in the animal models of diabetes and ischemia and reperfusion (I/R)- induced cardiac arrhythmias. Diabetes was induced in male rats with a single intraperitoneal injection of streptozotocin (60 mg/kg), rats were treated for two months with olive oil (1 ml/kg p.o). Control animals received saline. Blood glucose, body weight were monitored every 14 days. At the end of the treatment rats were sacrificed hearts were isolated for mounting on langedorff’s apparatus. The blood glucose and body weight was not significantly different in the control and olive treated animals. The control diabetic animals exhibited 100% incidence of I/R –induced ventricular fibrillation which was reduced to 0% with olive oil, treatment. The duration of ventricular fibrillation reduced from 98.8± 2.3 (control) to 0 seconds in the olive oil treated group. Diltiazem, a calcium channel blocker (1 µm/L) showed similar results and protected the I/R-induced cardiac disorders. The biochemical analysis of the cardiac tissues showed that diabetes and I/R produce marked pathological changes in the cardiomyocytes including decreased glutathione (GSH) and increased oxidative stress (Malondialdehyde; MDA). Pretreatment of animals with olive oil (1 ml/kg p.o) increased GSH and MDA levels. Olive oil also improved the diabetic-induced histopathological changes in the cardiomyocytes. These finding indicates that olive possesses cardiac protective properties. Further studies are under way in our lab to explore the mechanism of the cardio-protective effect of olive oil.

Keywords: diabeties, ischemia-reperfusion, olive oil, rats heart

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Authors: Maryam Bahreini, Mostafa Talebi Garekani, Fatemeh Rasooli, Atefeh Abdollahi

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Introduction: Procedural sedation and analgesia have been desirable to handle painful procedures. The trend to find the agent with more efficacy and less complications is still controversial; thus, many sedative regimens have been studied. This study tried to assess the effectiveness and adverse effects of thiopental sodium-fentanyl with the known medication, ketamine-propofol for procedural sedation in the emergency department. Methods: Consenting patients were enrolled in this randomized double-blind trial to receive either 1:1 ketamine-propofol (KP) or thiopental-fentanyl (TF) 1:1 mg: Mg proportion on a weight-based dosing basis to reach the sedation level of American Society of Anesthesiologist class III/IV. The respiratory and hemodynamic complications, nausea and vomiting, recovery agitation, patient recall and satisfaction, provider satisfaction and recovery time were compared. The study was registered in Iranian randomized Control Trial Registry (Code: IRCT2015111325025N1). Results: 96 adult patients were included and randomized, 47 in the KP group and 49 in the TF group. 2.1% in the KP group and 8.1 % in the TF group experienced transient hypoxia leading to performing 4.2 % versus 8.1 % airway maneuvers for 2 groups, respectively; however, no statistically significant difference was observed between 2 combinations, and there was no report of endotracheal placement or further admission. Patient and physician satisfaction were significantly higher in the KP group. There was no difference in respiratory, gastrointestinal, cardiovascular and psychiatric adverse events, recovery time and patient recall of the procedure between groups. The efficacy and complications were not related to the type of procedure or patients’ smoking or addiction trends. Conclusion: Ketamine-propofol and thiopental-fentanyl combinations were effectively comparable although KP resulted in higher patient and provider satisfaction. It is estimated that thiopental fentanyl combination can be as potent and efficacious as ketofol with relatively similar incidence of adverse events in procedural sedation.

Keywords: adverse effects, conscious sedation, fentanyl, propofol, ketamine, safety, thiopental

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Authors: Omar Khan, Shana Krstevska, Edwin George, Veronica Gorden, Fen Bao, Christina Caon, NP-C, Carla Santiago, Imad Zak, Navid Seraji-Bozorgzad

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Objective: To quantify cellular injury in the substantia nigra (SN) in patients with Parkinson's disease (PD) and to examine the effect of rasagiline of tissue injury in the SN in patients with PD. Background: N-acetylaspartate (NAA) quantified with MRS is a reliable marker of neuronal metabolic function. Fractional anisotropy (FA) and mean diffusivity (MD) obtained with DTI, characterize tissue alignment and integrity. Rasagline, has been shown to exert anti-apototic effect. We applied these advanced MRI techniques to examine: (i) the effect of rasagiline on cellular injury and metabolism in patients with early PD, and (ii) longitudinal changes seen over time in PD. Methods: We conducted a prospective longitudinal study in patients with mild PD, naive to dopaminergic treatment. The imaging protocol included multi-voxel proton-MRS and DTI of the SN, acquired on a 3T scanner. Scans were performed at baseline and month 3, during which the patient was on no treatment. At that point, rasagiline 1 mg orally daily was initiated and MRI scans are were obtained at 6 and 12 months after starting rasagiline. The primary objective was to compare changes during the 3-month period of “no treatment” to the changes observed “on treatment” with rasagiline at month 12. Age-matched healthy controls were also imaged. Image analysis was performed blinded to treatment allocation and period. Results: 25 patients were enrolled in this study. Compared to the period of “no treatment”, there was significant increase in the NAA “on treatment” period (-3.04 % vs +10.95 %, p= 0.0006). Compared to the period of “no treatment”, there was significant increase in following 12 month in the FA “on treatment” (-4.8% vs +15.3%, p<0.0001). The MD increased during “no treatment” and decreased in “on treatment” (+2.8% vs -7.5%, p=0.0056). Further analysis and clinical correlation are ongoing. Conclusions: Advanced MRI techniques quantifying cellular injury in the SN in PD is a feasible approach to investigate dopaminergic neuronal injury and could be developed as an outcome in exploratory studies. Rasagiline appears to have a stabilizing effect on dopaminergic cell loss and metabolism in the SN in PD, that warrants further investigation in long-term studies.

Keywords: substantia nigra, Parkinson's disease, MRI, neuronal loss, biomarker

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Authors: Jefferson S. Galanza, Jewel An Mischelle R.Camcam, Alyssa Karryl C. Co, Stephanie P. De Guzman, Jet Jet K. Dongui-is, Rodolfo Dane C. Frias, Ovelle C. Jueco, Harvey L. Matbagan, Victoria Luzette T. Rillon, Christelle Romyna H. Saruca, Jeanette Roma M. Villasper

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Background: Amidst numerous studies conducted on learning styles of students from a variety of courses, levels and school, a recent study recommended a great need for research on learning styles of student nurses. Moreover, related literatures have not been found exploring both the learning and teaching style of student nurses. Aims: The study aimed to determine the learning and teaching styles of student nurses and if there is an association between them. It also intended to discover whether student nurses are unimodal or multimodal in their styles and identified which faculty teaching style affords maximum outcome for student’s learning styles. Methods: Quantitative Descriptive-Correlational design was used. Participants were randomly selected 312 student nurses at School of Nursing X, Baguio City, Philippines. The questionnaire utilized a modified version of an adopted tool from Fleming’s VARK learning style version 7.2 (Visual, Auditory, Reader/Writer, Kinaesthetic) and Grasha’s teaching styles (Formal Authority, Demonstrator, Facilitator, Delegator). SPSS 19 was used for statistical treatment of data, where Chi square was used for the correlation of unimodal learning and teaching styles. Results/Finding: Majority of student nurses’ learning style is Kinesthetic and their teaching style is Demonstrator, which was also found to be significantly associated. Moreover, 8 out of 10 students are Unimodal in their learning and teaching modalities. In general, their preferred faculty teaching style is similar to their teaching style, which supports the concept, that teachers teach the way they learn. Conclusion: Study concludes that student nurses’ learning styles and teaching styles are varied, which exemplifies the uniqueness of every learner.This diversity in styles provided more evidence that a variety of mode of teaching and learning should be used by faculty and students to increase learning outcome and academic achievement. Recommendation: Future studies could be carried out in various schools of nursing utilizing faculty as respondents. Conduct assessment of learning style at the onset of classes/clinical placements so that faculty will become aware of the diversity of learners leading them to deliver diverse teaching methods.

Keywords: learning, learning styles, teaching styles, student nurses

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Authors: Kulsum Maula, Md Kamrul Alam, Md Ibrahim Khalil, Md Nazmul Hasan, Mohammad Omar Faruq

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Background: Percutaneous Tube Thoracostomy (PTT) is an invasive procedure that can save a life now and then in different traumatic and non-traumatic conditions. But still, it is an enigma; how our trainee surgeons are at home in this procedure. Objectives: To evaluate the outcome of the percutaneous tube thoracostomy performed by trainees in both trauma and non-trauma patients. Study design: Prospective, Observational Study. The duration of the study was September 2018 to February 2019. Methods: All patients who need PTT in traumatic and non-traumatic conditions were selected by purposive sampling. Thereafter, they were scrutinized according to eligibility criteria and 96 patients were finalized. A pre-tested, observation-based, peer-reviewed data collection sheet was prepared before the study. Data regarding clinical and surgical outcome profiles were recorded. Data were compiled, edited, and analyzed. Results: Among 96 patients, the highest 32.29% belonged to age group 31-40 years and the lowest 9.37% belonged to the age group ≤20. The mean age of the respondents was 29.19±9.81. We found out of 96 patients, 70(72.91%) were indicated PTT for traumatic conditions and the rest 26(27.08%) were indicated PTT for non-traumatic chest conditions, where 36(37.5%) had simple penumothorax, 21(21.87%) haemothorax, 14(14.58%) massive pleural effusion, 13(13.54%) tension pneumothorax, 10(10.41%) haemopneumothorax, and 2(2.08%) had pyothorax respectively. In 53.12% of patients had right-sided intercostal chest tube (ICT) insertion, whereas 46.87% had left-sided ICT insertion. In our study, 89.55 % of the tube was placed at the normal anatomical position. Besides, 10.41% of tube thoracostomy were performed deviated from anatomical site. Among 96 patients 62.5% patients had length of incision 2-3cm, 35.41% had >3cm and 2.08% had <2cm respectively. Out of 96 patients, 75(78.13%) showed uneventful outcomes, whereas 21(21.87%) had complications, including 11.15%(11) each had wound infection, 4.46%(4) subcutaneous emphysema, 4.28%(3) drain auto expulsion, 2.85%(2) hemorrhage, 1.45%(1) had a non-functioning drain and empyema with ascending infection respectively (p=<0.05). Conclusion: PTT is a life-saving procedure that is most frequently implemented in chest trauma patients in our country. In the majority of cases, the outcome of PTT was uneventful (78.13). Besides this, more than one-third of patients had a length of incision more than 3 cm that needed extra stitches and 10.41% of cases of PTT were placed other than the normal anatomical site. Trainees of Dhaka Medical College Hospitals are doing well in their performance of PTT insertion, but still, some anatomical orientations are necessary to avoid operative and post-operative complications.

Keywords: PTT, trainee, trauma, non-chest trauma patients

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Authors: Miceska Simona, Škof Erik, Frković Grazio Snježana, Jeričević Anja, Smrkolj Špela, Cvjetićanin Branko, Novaković Srdjan, Grčar Kuzmanov Biljana, Kloboves-Prevodnik Veronika

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Objectives: High-grade serous ovarian cancer (HGSOC) is characterized by the dissemination of the tumor cells (TC) in the peritoneal cavity forming malignant ascites at the time of diagnosis or recurrence. Still, cytology itself has been underutilized as a modality for the diagnosis of HGSOC from ascites, and histological examination from the tumor tissue is yet the only validated method used. The objective of this study was to evaluate the reliability of cytology in the diagnosis of HGSOC in relation to the histopathological examination. Methods: The study included 42 patients with histologically confirmed HGSOC, accompanied by malignant ascites. To confirm the malignancy of the TC in the ascites and to define their immunophenotype, immunohistochemical reaction (IHC) of the following antigens: Calretinin, MOC, WT1, PAX8, p53, p16 & Ki-67 was evaluated on ascites cytospins and tissue blocks. For complete cytological determination of HGSOC, BRCA 1/2 gene mutation was determined from ascites, tissue block, and blood. BRCA1/2 mutation from blood was performed to define the type of mutation, somatic vs germline. Results: Among 42 patients, the immunophenotype of HGSOC from ascites was confirmed in 36 cases (86%). For more profound analysis, the patients were divided in 3 groups regarding the number of TC present in the ascites: patients with less than 10% TC, 10% TC, and more than 10% TC. From all included patients, in the group with less than 10% TC, there were 10 cases, and only 5 of them(50%) showed HGSOC phenotype; 12 cases had equally 10% of TC, and 11 cases (92%) showed HGSOC phenotype; 20 cases had more than 10% TC and all of them (100%) confirmed the HGSOC immunophenotype from ascites. Only 33 patients were eligible for further BRCA1/2 analysis. Eleven BRCA1/2 mutations were detected from thetissue block: 6 germline and 5 somatic. In 2 cases with less than 10% TC, BRCA1/2 mutation was not detected; 4 cases had 10% TC, and 2 of them (50%) confirmed the mutation; 4 cases had more than 10% TC, and all showed 100% reliability with the tumor tissue. Conclusions: Cytology is a highly reliable method for determining the immunophenotype of HGSOC and BRCA1/2 mutation if more than 10% of tumor cells are present in the ascites. This may present an additional non-invasive clinical approach for fast and effective diagnose in the future, especially in inoperable conditions or relapses.

Keywords: cytology, ascites, high-grade serous ovarian cancer, immunophenotype, BRCA1/2

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Authors: AliAkbar Hafezi, Jamshid Abedi, Jalal Taherian, Behnam Kadkhodaei, Mahsa Elahi

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Background. Peripheral neuropathy is a common side effect of the administration of neurotoxic chemotherapy agents. This adverse effect is a major dose-limiting factor of many commonly used chemotherapy drugs. Currently, there are no Food and Drug Administration (FDA) approved medications for the prevention or treatment of chemotherapy-induced peripheral neuropathy. Therefore, this study was performed to investigate the efficacy and safety of metformin on paclitaxel-induced peripheral neuropathy (PIPN). Methods. In this randomized clinical trial, cancer patients who were candidates for chemotherapy with paclitaxel referred to the radiation oncology departments in Iran from 2022 to 2023 were studied. Patients were randomly divided into two groups; 1- Case group (n = 30) received metformin 500 mg orally twice a day after meals during chemotherapy with paclitaxel, and 2- Control group (30 people) received chemotherapy without metformin or any additional medication. Patients were visited in terms of numbness or other neurological symptoms two weeks before chemotherapy, 1-2 days before and weekly during chemotherapy, and at the end of the study. They were assessed by nerve conduction study (NCS) before intervention and one week after the end of chemotherapy. The primary outcome was the efficacy in reducing PIPN and the secondary outcome was adverse effects. Eventually, the outcomes were compared between the two groups of patients. Results. A total of 60 female cancer patients receiving chemotherapy with paclitaxel were evaluated in two groups. The groups were matched in terms of age, body mass index, fasting blood sugar, smoking, pathologic stage, and creatinine levels. The results showed that 18 patients (60.0 %) in the case group and 23 patients (76.6 %) in the control group had PIPN clinically (P = 0.267), and NCS showed 11 patients (36.6 %) in the case group and 15 patients (50.0 %) in the control group suffered from PIPN which no significant difference was observed between the two groups (P = 0.435). Diarrhea (n = 3; 10.0 %) and nausea (n = 3; 10.0 %) were the most common side effects of metformin in the case group and no serious side effects (lactic acidosis and anemia) were found in these patients. Conclusion. This study indicated that metformin did not significantly prevent PIPN in cancer patients receiving chemotherapy, although the frequency of peripheral neuropathy in the case group was lower than in the control group. The use of metformin in the patients had acceptable safety and no serious side effects were reported.

Keywords: peripheral neuropathy, chemotherapy, paclitaxel, metformin

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Authors: Jessica Chorostecki, Aashka Shah, Fen Bao, Ginny Bao, Edwin George, Navid Seraji-Bozorgzad, Veronica Gorden, Christina Caon, Elliot Frohman

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Background: Parkinson’s Disease (PD) is a neuro degenerative disorder associated with the loss of dopaminergic cells and the presence α-synuclein (AS) aggregation in of Lewy bodies. Both dopaminergic cells and AS are found in the retina. Optical coherence tomography (OCT) allows high-resolution in-vivo examination of retinal structure injury in neuro degenerative disorders including PD. Methods: We performed a cross-section OCT study in patients with definite PD and healthy controls (HC) using Spectral Domain SD-OCT platform to measure the peripapillary retinal nerve fiber layer (pRNFL) thickness and total macular volume (TMV). We performed intra-retinal segmentation with fully automated segmentation software to measure the volume of the RNFL, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), and the outer nuclear layer (ONL). Segmentation was performed blinded to the clinical status of the study participants. Results: 101 eyes from 52 PD patients (mean age 65.8 years) and 46 eyes from 24 HC subjects (mean age 64.1 years) were included in the study. The mean pRNFL thickness was not significantly different (96.95 μm vs 94.42 μm, p=0.07) but the TMV was significantly lower in PD compared to HC (8.33 mm3 vs 8.58 mm3 p=0.0002). Intra-retinal segmentation showed no significant difference in the RNFL volume between the PD and HC groups (0.95 mm3 vs 0.92 mm3 p=0.454). However, GCL, IPL, INL, and ONL volumes were significantly reduced in PD compared to HC. In contrast, the volume of OPL was significantly increased in PD compared to HC. Conclusions: Our finding of the enlarged OPL corresponds with mRNA expression studies showing localization of AS in the OPL across vertebrate species and autopsy studies demonstrating AS aggregation in the deeper layers of retina in PD. We propose that the enlargement of the OPL may represent a potential biomarker of AS aggregation in PD. Longitudinal studies in larger cohorts are warranted to confirm our observations that may have significant implications in disease monitoring and therapeutic development.

Keywords: Optical Coherence Tomography, biomarker, Parkinson's disease, alpha-synuclein, retina

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Authors: Ifigeneia V. Mavragani, Zacharenia Nikitaki, George Kalantzis, George Iliakis, Alexandros G. Georgakilas

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Complex DNA damage consisting of a combination of DNA lesions, such as Double Strand Breaks (DSBs) and non-DSB base lesions occurring in a small volume is considered as one of the most important biological endpoints regarding ionizing radiation (IR) exposure. Strong theoretical (Monte Carlo simulations) and experimental evidence suggests an increment of the complexity of DNA damage and therefore repair resistance with increasing linear energy transfer (LET). Experimental detection of complex (clustered) DNA damage is often associated with technical deficiencies limiting its measurement, especially in cellular or tissue systems. Our groups have recently made significant improvements towards the identification of key parameters relating to the efficient detection of complex DSBs and non-DSBs in human cellular systems exposed to IR of varying quality (γ-, X-rays 0.3-1 keV/μm, α-particles 116 keV/μm and 36Ar ions 270 keV/μm). The induction and processing of DSB and non-DSB-oxidative clusters were measured using adaptations of immunofluorescence (γH2AX or 53PB1 foci staining as DSB probes and human repair enzymes OGG1 or APE1 as probes for oxidized purines and abasic sites respectively). In the current study, Relative Biological Effectiveness (RBE) values for DSB and non-DSB induction have been measured in different human normal (FEP18-11-T1) and cancerous cell lines (MCF7, HepG2, A549, MO59K/J). The experimental results are compared to simulation data obtained using a validated microdosimetric fast Monte Carlo DNA Damage Simulation code (MCDS). Moreover, this simulation approach is implemented in two realistic clinical cases, i.e. prostate cancer treatment using X-rays generated by a linear accelerator and a pediatric osteosarcoma case using a 200.6 MeV proton pencil beam. RBE values for complex DNA damage induction are calculated for the tumor areas. These results reveal a disparity between theory and experiment and underline the necessity for implementing highly precise and more efficient experimental and simulation approaches.

Keywords: complex DNA damage, DNA damage simulation, protons, radiotherapy

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Authors: Mohammed Al-Zubaidi, Katherine Ong, Pravin Viswambaram, Steve McCombie, Oliver Oey, Jeremy Ong, Richard Gauci, Ronny Low, Dickon Hayne

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Objective: Lymph node involvement along with distant metastasis in a patient with invasive bladder cancer determines the disease survival, therefeor, it is an essential determinant of the therapeutic management and outcome. This retrospective study aims to determine the accuracy of FDG PET scan in detecting lymphatic involvement and distant metastatic urothelial cancer compared to conventional CT staging. Method: A retrospective review of 76 patients with UC or BC who underwent surgery or confirmatory biopsy that was staged with both CT and 18F-FDG-PET (up to 8 weeks apart) between 2015 and 2020. Fifty-sevenpatients (75%) had formal pelvic LN dissection or biopsy of suspicious metastasis. 18F-FDG-PET reports for positive sites were qualitative depending on SUV Max. On the other hand, enlarged LN by RECIST criteria 1.1 (>10 mm) and other qualitative findings suggesting metastasis were considered positive in CT scan. Histopathological findings from surgical specimens or image-guided biopsies were considered the gold standard in comparison to imaging reports. 18F-FDG-avid or enlarged pelvic LNs with surgically proven nodal metastasis were considered true positives. Performance characteristics of 18F-FDG-PET and CT, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (PPV), were calculated. Results: Pelvic LN involvement was confirmed histologically in 10/57 (17.5%) patients. Sensitivity, specificity, PPV and NPV of CT for detecting pelvic LN metastases were 41.17% (95% CI:18-67%), 100% (95% CI:90-100%) 100% (95% CI:59-100%) and 78.26% (95% CI:64-89%) respectively. Sensitivity, specificity, PPV and NPV of 18F-FDG-PET for detecting pelvic LN metastases were 62.5% (95% CI:35-85%), 83.78% (95% CI:68-94%), 62.5% (95% CI:35-85%), and 83.78% (95% CI:68-94%) respectively. Pre-operative staging with 18F-FDG-PET identified the distant metastatic disease in 9/76 (11.8%) patients who were occult on CT. This retrospective study suggested that 18F-FDG-PET may be more sensitive than CT for detecting pelvic LN metastases. 7/76 (9.2%) patients avoided cystectomy due to 18F-FDG-PET diagnosed metastases that were not reported on CT. Conclusion: 18F-FDG-PET is more sensitive than CT for pelvic LN metastases, which can be used as the standard modality of bladder cancer staging, as it may change the treatment by detecting lymph node metastasis that was occult in CT. Further research involving randomised controlled trials comparing the diagnostic yield of 18F-FDG-PET and CT in detecting nodal and distant metastasis in UC or BC is warranted to confirm our findings.

Keywords: FDG PET, CT scan, urothelial cancer, bladder cancer

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Authors: Robert Jedrys, Zdzislaw Kobos, Justyna Skrzynska, Zbigniew Wochynski

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Professions connected to aviation require an assessment of the suitability of health, psychological and psychomotor skills and overall physical fitness of the organism, who applies. Assessment of the physical condition is conducted by the committees consisting of aero-medical specialists in clinical medicine and aviation. In addition, psychological predispositions should be evaluated by specialized psychologists familiar with the specifics of the tasks and requirements for the various positions in aviation. Both, physical abilities and general physical fitness of candidates for aviation shall be assessed during the selection exams, which also test the ability to deal with stress what is very important in aviation. Hence, the mentioned exams in physical education not only help to judge on the ranking in candidates in terms of their efficiency and performance, but also allows to evaluate the functioning under stress measured using psychological tests. Moreover, before-test stress is a predictors of successfulness in the next stages of education and practical training in the aviation. The aim of the study was to evaluate the influence of temperamental traits on strategies used for coping with stress during selection exams in physical education, deciding on admission to aviation school. The study involved 30 candidates for fighter pilot training in aviation school . To evaluate the temperament 'The Formal Characteristics of Behavior-Temperament Inventory' (FCB-TI) by B. Zawadzki and J.Strelau was used. To determine the pattern of coping with stress 'The Coping Inventory for Stressful Situations' (CISS) to N. S. Endler and J. D. A. Parker were engaged. Study of temperament and styles of coping with stress was conducted directly before the exam selection of physical education. The results were analyzed with 'Statistica 9' program. The studies showed that:-There is a negative correlation between such a temperament feature as 'perseverance' and preferred style of coping with stress concentrated on the task (r = -0.590; p < 0.004); -There is a positive correlation between such a feature of temperament as 'emotional reactivity,' and preference to deal with a stressful situation with ‘style centered on emotions’ (r = 0.520; p <0.011); -There is a negative correlation between such a feature of temperament as ‘strength’ and ‘style of coping with stress concentrated on emotions’ (r = -0.580; p < 0.004). Studies indicate that temperament traits determine the perception of stress and preferred coping styles used during the selection, as during the exams in physical education.

Keywords: aviation, physical education, stress, temperamental traits

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Authors: Engin Berber, Nurettin Canakoglu, Ibrahim Sozdutmaz, Merve Caliskan, Shaikh Terkis Islam Pavel, Hazel Yetiskin, Aykut Ozdarendeli

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Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus in the family Bunyaviridae, genus Nairovirus. The CCHFV genome consists of three molecules of negative-sense single-stranded RNA, each encapsulated separately. The virion particle contains viral RNA polymerase (L segment), surface glycoproteins Gn and Gc (Msegment), and a nucleocapsid protein NP (S segment). CCHF is characterized by high case mortality, occurring in Asia, Africa, the Middle East and Eastern Europe. Clinical CCHF was first recognized in Turkey in 2002. The numbers of CCHF cases have gradually increased in Turkey making the virus a public health concern. Between 2002 and 2014, more than 8000 the CCHF cases have been reported in Turkey and mortality rate is around 5%. So, Turkey is one of the countries where the epidemy has become spread to the wider geography and the biggest outbreaks of CCHF have occurred in the world. We have recently developed an inactivated cell-culture based vaccine against CCHF. We have showed that the Balb/c mice immunized with the CCHF vaccine induced the high level of neutralizing antibodies. In this study, we aimed to determine the immunodominant regions of nucleoprotein (NP) CCHFV Kelkit06 strain which stimulate T cells. For this purpose, pools of overlapping NP were used for an IFN- γ ELISPOT assay. Balb/c mice were divided into two groups for the experiment. Two groups (n = 10 each) were immunized via the intraperitoneal route with 5, or 10μg of the cell culture-based vaccine. The control group (n = 6) was mock immunized with PBS. Booster injections with the same formulation were given on days 21 and 42 after the first immunization. The higher reactivity against the CCHFV NP pools 31-40 and 80-90 was determined in the two dose groups. In order to analyze the vaccine-induced T cell responses in Balb/c mice immunized with varying doses of the vaccine, we have been also currently working on CD4+, CD8+ and CD3 + T cells by flow cytometry.

Keywords: Crimean-Congo hemorrhagic fever virus, immunodominant regions of NP, T cell response, vaccine

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

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

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

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Authors: Carles Ferré, Ferran Llopis, Javier Jacob, Jordi Giol, Xavier Palom, Ignasi Bardés

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Objective: To analyze the characteristics of acute bacterial prostatitis (ABP) in elderly patients attended in the emergency department (ED). Methods: Observational and cohort study with prospective follow-up including patients with ABP presenting to the ED from January-December 2012. Data were collected for demographic variables, comorbidities, clinical and microbiological findings, treatment, outcome, and reconsultation at 30 days follow up. Findings were compared between patients ≥ 75 years (study group) and < 75 years (control group). Results: During the study period 241 episodes of ABP were included for analysis. Mean age was 62,9 ± 16 years, and 64 (26.5%) were ≥ 75 years old. A history of prostate adenoma was reported in 54 cases (22,4%), diabetes mellitus in 47 patients (19,5%) and prior manipulation of the lower urinary tract in 40 (17%). Mean symptoms duration was 3.38 ± 4.04 days, voiding symptoms were present in 176 cases (73%) and fever in 154 (64%). From 216 urine cultures, 128 were positive (59%) and 24 (17,6%) out of 136 blood cultures. Escherichia coli was the main pathogen in 58.6% of urine cultures and 64% of blood cultures (with resistant strains to fluoroquinolones in 27,7%, cotrimoxazole in 22,9% and amoxicillin/clavulanic in 27.7% of cases). Seventy patients (29%) were admitted to the hospital, and 3 died. At 30-day follow-up, 29 patients (12%) returned to the ED. In the bivariate analysis previous manipulation of the urinary tract, history of cancer, previous antibiotic treatment, resistant E. coli strains to amoxicillin-clavulanate and ciprofloxacin and extended spectrum beta-lactamase (ESBL) producers, renal impairment, and admission to the hospital were significantly more frequent (p < 0.05) among patients ≥ 75 years compared to those younger than 75 years. Conclusions: Ciprofloxacin and amoxicillin-clavulanate appear not to be good options for the empiric treatment of ABP for patients ≥ 75 years given the drug-resistance pattern in our series, and the proportion of ESBL-producing strains of E. coli should be taken into account. Awaiting bacteria identification and antibiogram from urine and/or blood cultures, treatment on an inpatient basis should be considered in older patients with ABP.

Keywords: acute bacterial prostatitits, antibiotic resistance, elderly patients, emergency

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Authors: Pronab Ganguly, Ahmed A. Moustafa

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Holistic management of schizophrenia involves mainstream pharmacological intervention, complimentary medicine intervention, therapeutic intervention and other psychosocial factors such as accommodation, education, job training, employment, relationship, friendship, exercise, overall well-being, smoking, substance abuse, suicide prevention, stigmatisation, recreation, entertainment, violent behaviour, arrangement of public trusteeship and guardianship, day-day-living skill, integration with community, and management of overweight due to medications and other health complications related to medications amongst others. Our review shows that there is no integrated survey by combining all these factors. An international web-based survey was conducted to evaluate the significance of all these factors and present them in a unified manner. It is believed this investigation will contribute positively towards holistic management of schizophrenia. There will be two surveys. In the pharmacological intervention survey, five popular drugs for schizophrenia will be chosen and their efficacy as well as harmful side effects will be evaluated on a scale of 0 -10. This survey will be done by psychiatrists. In the second survey, each element of therapeutic intervention and psychosocial factors will be evaluated according to their significance on a scale of 0 - 10. This survey will be done by care givers, psychologists, case managers and case workers. For the first survey, professional bodies of psychiatrists in English speaking countries will be contacted to request them to ask their members to participate in the survey. For the second survey, professional bodies of clinical psychologist and care givers in English speaking countries will be contacted to request them to ask their members to participate in the survey. Additionally, for both the surveys, relevant professionals will be contacted through personal contact networks. For both the surveys, mean, mode, median, standard deviation and net promoter score will be calculated for each factor and then presented in a statistically significant manner. Subsequently each factor will be ranked according to their statistical significance. Additionally, country specific variation will be highlighted to identify the variation pattern. The results of these surveys will identify the relative significance of each type of pharmacological intervention, each type of therapeutic intervention and each type of psychosocial factor. The determination of this relative importance will definitely contribute to the improvement in quality of life for individuals with schizophrenia.

Keywords: schizophrenia, holistic management, antipsychotics, quality of life

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Authors: S. Pathak, R. Lazarus

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A 25-year-old male HIV patient (CD4 cells 20/µL and HIV viral load 14200000 copies/ml) with a past medical history of duodenal ulcer, pneumocystis carinii pneumonia, oesophageal candidiasis presented with fever and a seizure to hospital. The only recent travel had been a religious pilgrimage from Singapore to Malaysia 5 days prior; during the trip he sustained skin abrasions. The patient had recently started highly active antiretroviral therapy 2 months prior. Clinical examination was unremarkable other than a temperature of 38.8°C and perianal warts. Laboratory tests showed a leukocyte count 12.5x109 cells/L, haemoglobin 9.4 g/dL, normal biochemistry and a C-reactive protein 121 mg/L. CT head and MRI head were unremarkable and cerebrospinal fluid analysis performed after a delay (due to technical difficulties) of 11 days was unremarkable. Blood cultures (three sets) taken on admission showed Gram-negative rods in the anaerobic bottles only at the end of incubation with culture result confirmed by molecular sequencing showing Helicobacter cinaedi. The patient was treated empirically with ceftriaxone for seven days and this was converted to oral co-amoxiclav for a further seven days after the blood cultures became positive. A Transthoracic echocardiogram was unremarkable. The patient made a full recovery. Helicobacter cinaedi is a gram-negative anaerobic fastidious organism affecting patients with comorbidity. Infection may manifest as cellulitius, colitis or as in this case as bloodstream infection – the latter is often attributed to faeco-oral infection. Laboratory identification requires prolonged culture. Therapeutic options may be limited by resistance to macrolides and fluoroquinolones. The likely pathogen inoculation routes in the case described include gastrointestinal translocation due to proctitis at the site of perianal warts, or breach of the skin via abrasions occurring during the pilgrimage. Such organisms are increasing in prevalence as our patient population ages and patients have multiple comorbidities including HIV. It may be necessary in patients with unexplained fever to prolong incubation of sterile sites including blood in order to identify this unusual fastidious organism.

Keywords: fastidious, Helicobacter cinaedi, HIV, immunocompromised

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Authors: Lucie Côté, Martin Lauzier, Guy Beauchamp, France Guertin

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Stress causes deleterious effects to the physical, psychological and organizational levels, which highlight the need to use effective coping strategies to deal with it. Several coping models exist, but they don’t integrate the different strategies in a coherent way nor do they take into account the new research on the emotional coping and acceptance of the stressful situation. To fill these gaps, an integrative model incorporating the main coping strategies was developed. This model arises from the review of the scientific literature on coping and from a qualitative study carried out among workers with low or high levels of stress, as well as from an analysis of clinical cases. The model allows one to understand under what circumstances the strategies are effective or ineffective and to learn how one might use them more wisely. It includes Specific Strategies in controllable situations (the Modification of the Situation and the Resignation-Disempowerment), Specific Strategies in non-controllable situations (Acceptance and Stubborn Relentlessness) as well as so-called General Strategies (Wellbeing and Avoidance). This study is intended to undertake and present the process of development and validation of an instrument to measure coping strategies based on this model. An initial pool of items has been generated from the conceptual definitions and three expert judges have validated the content. Of these, 18 items have been selected for a short form questionnaire. A sample of 300 students and employees from a Quebec university was used for the validation of the questionnaire. Concerning the reliability of the instrument, the indices observed following the inter-rater agreement (Krippendorff’s alpha) and the calculation of the coefficients for internal consistency (Cronbach's alpha) are satisfactory. To evaluate the construct validity, a confirmatory factor analysis using MPlus supports the existence of a model with six factors. The results of this analysis suggest also that this configuration is superior to other alternative models. The correlations show that the factors are only loosely related to each other. Overall, the analyses carried out suggest that the instrument has good psychometric qualities and demonstrates the relevance of further work to establish predictive validity and reconfirm its structure. This instrument will help researchers and clinicians better understand and assess coping strategies to cope with stress and thus prevent mental health issues.

Keywords: acceptance, coping strategies, stress, validation process

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Authors: Chih-Chung Huang, Po-Hsun Peng

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Ultrasound transient elastography has become a valuable tool for many clinical diagnoses, such as liver diseases and breast cancer. The pathological tissue can be distinguished by elastography due to its stiffness is different from surrounding normal tissues. An ultrafast frame rate of ultrasound imaging is needed for transient elastography modality. The elastography obtained in the ultrafast system suffers from a low quality for resolution, and affects the robustness of the transient elastography. In order to overcome these problems, a coherent plane wave compounding technique has been proposed for conventional ultrasound system which the operating frequency is around 3-15 MHz. The purpose of this study is to develop a novel beamforming technique for high frequency ultrasound coherent plane-wave compounding imaging and the simulated results will provide the standards for hardware developments. Plane-wave compounding imaging produces a series of low-resolution images, which fires whole elements of an array transducer in one shot with different inclination angles and receives the echoes by conventional beamforming, and compounds them coherently. Simulations of plane-wave compounding image and focused transmit image were performed using Field II. All images were produced by point spread functions (PSFs) and cyst phantoms with a 64-element linear array working at 35MHz center frequency, 55% bandwidth, and pitch of 0.05 mm. The F number is 1.55 in all the simulations. The simulated results of PSFs and cyst phantom which were obtained using single, 17, 43 angles plane wave transmission (angle of each plane wave is separated by 0.75 degree), and focused transmission. The resolution and contrast of image were improved with the number of angles of firing plane wave. The lateral resolutions for different methods were measured by -10 dB lateral beam width. Comparison of the plane-wave compounding image and focused transmit image, both images exhibited the same lateral resolution of 70 um as 37 angles were performed. The lateral resolution can reach 55 um as the plane-wave was compounded 47 angles. All the results show the potential of using high-frequency plane-wave compound imaging for realizing the elastic properties of the microstructure tissue, such as eye, skin and vessel walls in the future.

Keywords: plane wave imaging, high frequency ultrasound, elastography, beamforming

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Authors: Adnan A. Kadi, Nasser S. Al-Shakliah, Haitham Al-Rabiah

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Zorifertinib is a novel, potent, oral, a small molecule used to treat non-small cell lung cancer (NSCLC). zorifertinib is an Epidermal Growth Factor Receptor (EGFR) inhibitor and has good blood–brain barrier permeability for (NSCLC) patients with EGFR mutations. zorifertinibis currently at phase II/III clinical trials. The current research reports the characterization and identification of in vitro, in vivo and reactive intermediates of zorifertinib. Prediction of susceptible sites of metabolism and reactivity pathways (cyanide and GSH) of zorifertinib were performed by the Xenosite web predictor tool. In-vitro metabolites of zorifertinib were performed by incubation with rat liver microsomes (RLMs) and isolated perfused rat liver hepatocytes. Extraction of zorifertinib and it's in vitro metabolites from the incubation mixtures were done by protein precipitation. In vivo metabolism was done by giving a single oral dose of zorifertinib(10 mg/Kg) to Sprague Dawely rats in metabolic cages by using oral gavage. Urine was gathered and filtered at specific time intervals (0, 6, 12, 18, 24, 48, 72,96and 120 hr) from zorifertinib dosing. A similar volume of ACN was added to each collected urine sample. Both layers (organic and aqueous) were injected into liquid chromatography ion trap mass spectrometry(LC-IT-MS) to detect vivozorifertinib metabolites. N-methyl piperizine ring and quinazoline group of zorifertinib undergoe metabolism forming iminium and electro deficient conjugated system respectively, which are very reactive toward nucleophilic macromolecules. Incubation of zorifertinib with RLMs in the presence of 1.0 mM KCN and 1.0 Mm glutathione were made to check reactive metabolites as it is often responsible for toxicities associated with this drug. For in vitro metabolites there were nine in vitro phase I metabolites, four in vitro phase II metabolites, eleven reactive metabolites(three cyano adducts, five GSH conjugates metabolites, and three methoxy metabolites of zorifertinib were detected by LC-IT-MS. For in vivo metabolites, there were eight in vivo phase I, tenin vivo phase II metabolitesofzorifertinib were detected by LC-IT-MS. In vitro and in vivo phase I metabolic pathways wereN- demthylation, O-demethylation, hydroxylation, reduction, defluorination, and dechlorination. In vivo phase II metabolic reaction was direct conjugation of zorifertinib with glucuronic acid and sulphate.

Keywords: in vivo metabolites, in vitro metabolites, cyano adducts, GSH conjugate

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

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

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

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Authors: Shashi Sharma, V. K. Katiyar, Uaday Singh

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The ability to manipulate magnetic particles in fluid flows by means of inhomogeneous magnetic fields is used in a wide range of biomedical applications including magnetic drug targeting (MDT). In MDT, magnetic carrier particles bounded with drug molecules are injected into the vascular system up-stream from the malignant tissue and attracted or retained at the specific region in the body with the help of an external magnetic field. Although the concept of MDT has been around for many years, however, wide spread acceptance of the technique is still looming despite the fact that it has shown some promise in both in vivo and clinical studies. This is because traditional MDT has some inherent limitations. Typically, the magnetic force is not very strong and it is also very short ranged. Since the magnetic force must overcome rather large hydrodynamic forces in the body, MDT applications have been limited to sites located close to the surface of the skin. Even in this most favorable situation, studies have shown that it is difficult to collect appreciable amounts of the MDCPs at the target site. To overcome these limitations of the traditional MDT approach, Ritter and co-workers reported the implant assisted magnetic drug targeting (IA-MDT). In IA-MDT, the magnetic implants are placed strategically at the target site to greatly and locally increase the magnetic force on MDCPs and help to attract and retain the MDCPs at the targeted region. In the present work, we develop a mathematical model to study the capturing of magnetic nanoparticles flowing in a fluid in an implant assisted cylindrical channel under the magnetic field. A coil of ferromagnetic SS 430 has been implanted inside the cylindrical channel to enhance the capturing of magnetic nanoparticles under the magnetic field. The dominant magnetic and drag forces, which significantly affect the capturing of nanoparticles, are incorporated in the model. It is observed through model results that capture efficiency increases from 23 to 51 % as we increase the magnetic field from 0.1 to 0.5 T, respectively. The increase in capture efficiency by increase in magnetic field is because as the magnetic field increases, the magnetization force, which is attractive in nature and responsible to attract or capture the magnetic particles, increases and results the capturing of large number of magnetic particles due to high strength of attractive magnetic force.

Keywords: capture efficiency, implant assisted-magnetic drug targeting (IA-MDT), magnetic nanoparticles, modelling

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Authors: Neşe Alkan

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Purpose: The point that applied/clinical psychology, which is the practice and research discipline of the mental health field, has reached today can be summarized as the necessity of handling the psychological well-being of people from multiple perspectives and the goal of moving it to a higher level. Clients' subjective assessment of their own condition and wellbeing is an integral part of evidence-based interventions. There is a need for tools through which clients can evaluate the effectiveness of the psychotherapy/intervention performed with them and their contribution to the wellbeing and wellbeing of this process in a valid and reliable manner. The aim of this research is to meet this need, to test the reliability and validity of the index in Turkish, and explore its usability in the practices of both researchers and psychotherapists. Method: A total of 213 adults aged between 18-54, 69.5% working and 29.5% university students, were included in the study. Along with their demographic information, the participants were administered a set of scales: wellbeing, life satisfaction, spiritual satisfaction, shopping addiction, and loneliness, namely via an online platform. The construct validity of the wellbeing scale was tested with exploratory and confirmatory factor analyses, convergent and discriminant validity were tested with two-way full and partial correlation analyses and, measurement invariance was tested with one-way analysis of variance. Results: Factor analyzes showed that the scale consisted of six dimensions as it is in its original structure. The internal consistency of the scale was found to be Cronbach α = .82. Two-way correlation analyzes revealed that the wellbeing scale total score was positively correlated with general life satisfaction (r = .62) and spiritual satisfaction (r = .29), as expected. It was negatively correlated with loneliness (r = -.51) and shopping addiction (r = -.15). While the scale score did not vary by gender, previous illness, or nicotine addiction, it was found that the total wellbeing scale scores of the participants who had used antidepressant medication during the past year were lower than those who did not use antidepressant medication (F(1,204) = 7.713, p = .005). Conclusion: It has been concluded that the 12-item wellbeing scale consisting of six dimensions can be used in research and health sciences practices as a valid and reliable measurement tool. Further research which examines the reliability and validity of the scale in different widely used languages such as Spanish and Chinese is recommended.

Keywords: wellbeing, intervention effectiveness, reliability and validity, effectiveness

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Authors: John Acord, Ankita Batla, Kiran Khepar, Maude Schmidt, Charlotte Allen, Russ Bradford

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Objectives: Despite the availability oftreatment options, Parkinson’s disease (PD) continues to impact heavily on a patient’s quality of life (QoL), as many symptoms that bother the patient remain unexplored and untreated in clinical settings. The aims of this research were to understand the burden of PDsymptoms from a patient perspective, particularly those which are the most persistent and debilitating, and to determine if current treatments and treatment algorithms adequately focus on their resolution. Methods: A13-question, online, patient-reported survey was created based on the MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS)and symptoms listed on Parkinson’s Disease Patient Advocacy Groups websites, and then validated by 10 Parkinson’s patients. In the survey, patients were asked to choose both their most common and their most bothersome symptoms, whether they had received treatment for those and, if so, had it been effective in resolving those symptoms. Results: The most bothersome symptoms reported by the 111 participants who completed the survey were sleep problems (61%), feeling tired (56%), slowness of movements (54%), and pain in some parts of the body (49%). However, while 86% of patients reported receiving dopamine or dopamine like drugs to treat their PD, far fewer reported receiving targeted therapies for additional symptoms. For example, of the patients who reported having sleep problems, only 33% received some form of treatment for this symptom. This was also true for feeling tired (30% received treatment for this symptom), slowness of movements (62% received treatment for this symptom), and pain in some parts of the body (61% received treatment for this symptom). Additionally, 65% of patients reported that the symptoms they experienced were not adequately controlled by the treatments they received, and 9% reported that their current treatments had no effect on their symptoms whatsoever. Conclusion: The survey outcomes highlight that the majority of patients involved in the study received treatment focused on their disease, however, symptom-based treatments were less well represented. Consequently, patient-reported symptoms such as sleep problems and feeling tired tended to receive more fragmented intervention than ‘classical’ PD symptoms, such as slowness of movement, even though they were reported as being amongst the most bothersome symptoms for patients. This research highlights the need to explore symptom burden from the patient’s perspective and offer Customised treatment/support for both motor and non-motor symptoms maximize patients’ quality of life.

Keywords: survey, patient reported symptom burden, unmet needs, parkinson's disease

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Authors: Nuruddin Mohammod Zahangir, Syed Tanvir Ahmady, Firoz Ahmed, Mainul Kabir, Tamjid Mohammad Najmus Sakib Khan, Nazmul Hossain, Niaz Ahmed, Madhava Janardhan Naik

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The management of combined Coronary Artery Disease and Peripheral Vascular Disease is a challenge and brings with it numerous clinical dilemmas.The 56 year old gentleman presented to our department with significant triple vessel disease with occluded lower end of aorta just before bifurcation and bilateral superficial femoral arteries. Operation was done on 11.03.14. The The Left Internal Mammary Artery (LIMA) and the Right Internal Mammary Artery (RIMA) were harvested in skeletonized manner. The free RIMA was then anastomosed with LIMA to make LIMA-RIMA Y. Cardio Pulmonary Bypass was then established and coronary artery bypass grafts performed. LIMA was anastomosed to the Left Anterior Descending artery. RIMA was anastomosed to Posterior Descending Artery, 1st and 2nd Obtuse Marginal arteries in a sequential manner. Abdomen was opened by midline incision. The infrarenal aorta exposed and was found to be severely diseased. A Vascular Clamp was applied infrarenally, aortotomy done and limited endarterectomy performed. An end-to-side anastomosis was done with upper end of PTFE synthetic Y-graft (14/7 mm) to the infarenal Aorta and the Clamp released. Good flow noted in both limbs of the graft. Patient was then slowly weaned off from Cardio Pulmonary Bypass without difficulty. The distal two limbs of the Y graft were passed to the groin through retroperitoneal tunnels and anastomosed end-to-side with the common femoral arteries. Saphenous vein was interposed between common femoral and popliteal arteries bilaterally through subfascial tunnels in both thigh. On 12th postoperative day he was discharged from hospital in good general condition. Follow up after 3 months of operation the patient is doing good and free of chest pain and claudication pain.

Keywords: total arterial, coronary revascularization, aorto-bifemoral bypass, bifemoro-bipopliteal bypass

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Authors: Semira Zeru Haileslassie

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Lack of awareness and practices of PEP treatment were observed among respondents, but they had a better attitude towards PEP. To this end, a formal training for all respondents regarding PEP for HIV prior to their clinical attachments is of utmost importance. The training ought to incorporate a brief clarification with respect to the unpleasant impact of non-adherence that essentially incorporate destitute treatment result and most prominent hazard of resistance and few given as a major cause for non-compliance to PEP, common transient side-effects of PEP and its administrations ought to be cloister educated healthcare specialists to diminish its effect on adherence. Besides, the propensity of detailing needle adhere harm was destitute that needs endeavors to progress. Progressing the culture of detailing and making the detailing handle simple is very necessary. In reality, announcing such wounds as early as conceivable will educate others not to commit same issue once more and, for the most part, will empower stakeholders to intercede the issue sometime prior to it re-occur. At long last, as distant as get up and go utilize has cleared out with so numerous bothers, risk decrease is the foremost choice. With this, taking the increased significance of protective barriers so as to decrease the hazard of exposure to HIV, distinctive stakeholders (the healing center hardware supply chain director, the HIV/ Helps clinic, the clinic chief, hardware and supply quality confirmation group, and other authoritative bodies) ought to work together in co-ordination to secure the supply and guarantee the quality of those crucial protective barriers and to advance demand health laborers to continuously wear protective barriers when exposed to HIV hazard components as well as to dispose appropriately once done. At long last, we prescribe future examiners to conduct planned multicenter studies with extra goals (counting indicator investigation) for way better generalization and result. In spite of satisfactory information and favorable state of mind towards PEP for HIV in most of the respondents, this study uncovered that there were delays in starting, low utilization, and fragmented use of the prescribed PEP. So, health care staff need to progress their practice on PEP of HIV through diverse training program related to PEP of HIV.

Keywords: HIV infection, prophylaxis, knowledge, attitude

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Authors: Chengcao Sun, Cuili Yang, Shujun Li, Ruilin Xue, Liang Wang, Yongyong Xi, Dejia Li

Abstract:

Backgrounds: Sulforaphane, one of the most important isothiocyanates in the human diet, is known to have chemopreventive and antioxidant activities in different tissues via activation of NF-E2-related factor 2 (Nrf2)-mediated induction of antioxidant/phase II enzymes, such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). However, its effects on muscular dystrophy remain unknown. This work was undertaken to evaluate the effects of Sulforaphane on Duchenne muscular dystrophy (DMD). Methods: 4-week-old mdx mice were treated with SFN by gavage (2 mg/kg body weight per day) for 8 weeks. Blood was collected from eye socket every week, and tibial anterior, extensor digitorum longus, gastrocnemius, soleus, triceps brachii muscles and heart samples were collected after 8-week gavage. Force measurements and mice exercise capacity assays were detected. GSH/GSSG ratio, TBARS, CK and LDH levels were analyzed by spectrophotometric methods. H&E staining was used to analyze histological and morphometric of skeletal muscles of mdx mice, and Evas blue dye staining was made to detect sarcolemmal integrity of mdx mice. Further, the role of Sulforaphane on Nrf2/ARE signaling pathway was analyzed by ELISA, western blot and qRT-PCR. Results: Our results demonstrated that SFN treatment increased the expression and activity of muscle phase II enzymes NQO1 and HO-1 with Nrf2 dependent manner. SFN significantly increased skeletal muscle mass, muscle force (~30%), running distance (~20%) and GSH/GSSG ratio (~3.2 folds) of mdx mice, and decreased the activities of plasma creatine phosphokinase (CK) (~45%) and lactate dehydrogenase (LDH) (~40%), gastrocnemius hypertrophy (~25%), myocardial hypertrophy (~20%) and MDA levels (~60%). Further, SFN treatment also reduced the central nucleation (~40%), fiber size variability, inflammation and improved the sarcolemmal integrity of mdx mice. Conclusions: Collectively, these results show that SFN can improve muscle function, pathology and protect dystrophic muscle from oxidative damage in mdx mice through Nrf2 signaling pathway, which indicate Nrf2 may have clinical implications for the treatment of patients with muscular dystrophy.

Keywords: sulforaphane, duchenne muscular dystrophy, Nrf2, oxidative stress

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