Search results for: clinical depression

Authors: Abdul Qadir Jangda, Khadija Mariam, Usman Ahmed, Sharib Ahmed

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The Gafchromic EBT3 film has the characteristic of high spatial resolution, weak energy dependence and near tissue equivalence which makes them viable to be used for in-vivo dosimetry in External Beam and Brachytherapy applications. The aim of this study is to assess the smallest film dimension that may be feasible for the use in in-vivo dosimetry. To evaluate the viability, the film sizes from 3 x 3 mm to 20 x 20 mm were calibrated with 6 MV Photon and 6 MeV electron beams. The Gafchromic EBT3 (Lot no. A05151201, Make: ISP) film was cut into five different sizes in order to establish the relationship between absorbed dose vs. film dimensions. The film dimension were 3 x 3, 5 x 5, 10 x 10, 15 x 15, and 20 x 20 mm. The films were irradiated on Varian Clinac® 2100C linear accelerator for dose range from 0 to 1000 cGy using PTW solid water phantom. The irradiation was performed as per clinical absolute dose rate calibratin setup, i.e. 100 cm SAD, 5.0 cm depth and field size of 10x10 cm2 and 100 cm SSD, 1.4 cm depth and 15x15 cm2 applicator for photon and electron respectively. The irradiated films were scanned with the landscape orientation and a post development time of 48 hours (minimum). Film scanning accomplished using Epson Expression 10000 XL Flatbed Scanner and quantitative analysis carried out with ImageJ freeware software. Results show that the dose variation with different film dimension ranging from 3 x 3 mm to 20 x 20 mm is very minimal with a maximum standard deviation of 0.0058 in Optical Density for a dose level of 3000 cGy and the the standard deviation increases with the increase in dose level. So the precaution must be taken while using the small dimension films for higher doses. Analysis shows that there is insignificant variation in the absorbed dose with a change in film dimension of EBT3 film. Study concludes that the film dimension upto 3 x 3 mm can safely be used up to a dose level of 3000 cGy without the need of recalibration for particular dimension in use for dosimetric application. However, for higher dose levels, one may need to calibrate the films for a particular dimension in use for higher accuracy. It was also noticed that the crystalline structure of the film got damage at the edges while cutting the film, which can contribute to the wrong dose if the region of interest includes the damage area of the film

Keywords: external beam radiotherapy, film calibration, film dosimetery, in-vivo dosimetery

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Authors: Yosep Chong, Yejin Kim, Jingyun Choi, Hwanjo Yu, Eun Jung Lee, Chang Suk Kang

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For the past decades, immunohistochemistry (IHC) has been playing an important role in the diagnosis of human neoplasms, by helping pathologists to make a clearer decision on differential diagnosis, subtyping, personalized treatment plan, and finally prognosis prediction. However, the IHC performed in various tumors of daily practice often shows conflicting and very challenging results to interpret. Even comprehensive diagnosis synthesizing clinical, histologic and immunohistochemical findings can be helpless in some twisted cases. Another important issue is that the IHC data is increasing exponentially and more and more information have to be taken into account. For this reason, we reached an idea to develop an expert supporting system to help pathologists to make a better decision in diagnosing human neoplasms with IHC results. We gave probabilistic decision tree algorithm and tested the algorithm with real case data of lymphoid neoplasms, in which the IHC profile is more important to make a proper diagnosis than other human neoplasms. We designed probabilistic decision tree based on Bayesian theorem, program computational process using MATLAB (The MathWorks, Inc., USA) and prepared IHC profile database (about 104 disease category and 88 IHC antibodies) based on WHO classification by reviewing the literature. The initial probability of each neoplasm was set with the epidemiologic data of lymphoid neoplasm in Korea. With the IHC results of 131 patients sequentially selected, top three presumptive diagnoses for each case were made and compared with the original diagnoses. After the review of the data, 124 out of 131 were used for final analysis. As a result, the presumptive diagnoses were concordant with the original diagnoses in 118 cases (93.7%). The major reason of discordant cases was that the similarity of the IHC profile between two or three different neoplasms. The expert supporting system algorithm presented in this study is in its elementary stage and need more optimization using more advanced technology such as deep-learning with data of real cases, especially in differentiating T-cell lymphomas. Although it needs more refinement, it may be used to aid pathological decision making in future. A further application to determine IHC antibodies for a certain subset of differential diagnoses might be possible in near future.

Keywords: database, expert supporting system, immunohistochemistry, probabilistic decision tree

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Authors: Ifeoma C. Afiaenyi, Elizabeth K. Ngwu, Rufina N. B. Ayogu

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Diabetes has crept into the rural areas of Nigeria, causing devastating effects on its sufferers; most of them could not afford diabetic medications. Moringa oleifera has been used extensively in animal models to demonstrate its antilipidaemic and haematinic qualities; however, there is a scarcity of data on the effect of graded levels of Moringa oleifera leaves on the lipid profile and hematological parameters in human diabetic subjects. The study determined the effect of Moringa oleifera leaves on the lipid profile and hematological parameters of type 2 diabetic subjects in Ukehe, a rural Nigerian community. Twenty-four adult male and female diabetic subjects were purposively selected for the study. These subjects were shared into four groups of six subjects each. The diets used in the study were isocaloric. A control group (diabetics, group 1) was fed diets without Moringa oleifera leaves. Experimental groups 2, 3 and 4 received 20g, 40g and 60g of Moringa oleifera leaves daily, respectively, in addition to the diets. The subjects' lipid profile and hematological parameters were measured prior to the feeding trial and at the end of the feeding trial. The feeding trial lasted for fourteen days. The data obtained were analyzed using the computer program Statistical Product for Service Solution (SPSS) for windows version 21. A Paired-samples t-test was used to compare the means of values collected before and after the feeding trial within the groups and significance was accepted at p < 0.05. There was a non-significant (p > 0.05) decrease in the mean total cholesterol of the subjects in groups 1, 2 and 3 after the feeding trial. There was a non-significant (p > 0.05) decrease in the mean triglyceride levels of the subjects in group 1 after the feeding trial. Groups 1 and 3 subjects had a non-significant (p > 0.05) decrease in their mean low-density lipoprotein (LDL) cholesterol after the feeding trial. Groups 1, 2 and 4 had a significant (p < 0.05) increase in their mean high-density lipoprotein (HDL) cholesterol after the feeding trial. A significant (p < 0.05) decrease in the mean hemoglobin level was observed only in group 4 subjects. Similarly, there was a significant (p < 0.05) decrease in the mean packed cell volume of group 4 subjects. It was only in group 4 that a significant (p < 0.05) decrease in the mean white blood cells of the subjects was also observed. The changes observed in the parameters assessed were not dose-dependent. Therefore, a similar study of longer duration and more samples is imperative to authenticate these results.

Keywords: anemia, diabetic subjects, lipid profile, moringa oleifera

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Authors: Nura Brimo, Dilek Cokeliler Serdaroglu, Tansel Uyar, Busra Uysal, Elif Bahar Cakici, Miris Dikmen, Zerrin Canturk

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Background: A combination of antibiotics, including metronidazole (MET), ciprofloxacin (CIP), and minocycline (MINO), has been demonstrated to disinfect bacteria in necrotic teeth before regenerative processes. It has been presented clinically that antibiotic pastes may drive to possible stem cell death and difficulties in removing from the canal system, which can limit the regenerative procedure. This study was designed to (1) synthesize nanofibrous webs containing various concentrations of different medicaments (triple, double, and calcium hydroxide,Ca(OH)2), and (2) coat thiselectrospun fibrous gutta-percha (GP) cones. Methods: Poly(vinylpyrrolidone) (PVP)-based electrospun fibrous webs were processed with low medicaments concentrations. Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDX), and X-Ray Photoelectron Spectroscopy (XPS) were carried out to investigate fiber morphology, antibiotic incorporation, and characterized GP-coated fibrous webs, respectively. The chemical and physical properties of dentine were carried out via Fourier Transform Infrared Spectroscopy (FTIR) and Nano-SEM, respectively. The antimicrobial properties of the different fibrous webs were assessed against various bacteria by direct nanofiber/bacteria contact. Cytocompatibility was measured by applying the MTT method. Results: The mean fiber diameter of the experiment groups of medicament-containing fibers ranged in the nm scale and was significantly smaller than PVP fibers. EDX analysis confirmed the presence of medicaments in the nanofibers. XPS analysis presented a complete coating of the fibers with GPs; FTIR and Nano-SEM showed no chemical and physical configuration of intracanal medicaments on the dentine surface. Meanwhile, nanofibrous webs led to a significant reduction in the percentage of viable bacteria compared with the negative control and PVP. Conclusion: Our findings suggest that TA-NFs, DA-NFs, and Cₐ(OH)₂)-NFs coated GP cones have significant potential in eliminating intracanal bacteria, cell-friendly behavior, and clinical usage features.

Keywords: drug delivery, drug carrier, electrospinning, nano/microfibers, regenerative endodontic, morphology

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Authors: Alireza Hassanshahi, Xanthe Strudwick, Zlatko Kopecki, Allison J Cowin

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Studies have shown that Flightless (Flii) is elevated in human wounds, including burns, and reducing the level of Flii is a promising approach for improving wound repair and reducing scar formation. The most effective approach has been to neutralise Flii activity using localized, intradermal application of function blocking monoclonal antibodies. However, large surface area burns are difficult to treat by intradermal injection of therapeutics, so the aim of this study was to investigate if a systemic injection of a monoclonal antibody against Flii could improve healing in mice following burn injury. Flii neutralizing antibodies (FnAbs) were labelled with Alxa-Fluor-680 for biodistribution studies and the healing effects of systemically administered FnAbs to mice with burn injuries. A partial thickness, 7% (70mm2) total body surface area scald burn injury was created on the dorsal surface of mice (n=10/group), and 100µL of Alexa-Flour-680-labeled FnAbs were injected into the intraperitoneal cavity (IP) at time of injury. The burns were imaged on days 0, 1, 2, 3, 4, and 7 using IVIS Lumina S5 Imaging System, and healing was assessed macroscopically, histologically, and using immunohistochemistry. Fluorescent radiance efficiency measurements showed that IP injected Alexa-Fluor-680-FnAbs localized at the site of burn injury from day 1, remaining there for the whole 7-day study. The burns treated with FnAbs showed a reduction in macroscopic wound area and an increased rate of epithelialization compared to controls. Immunohistochemistry for NIMP-R14 showed a reduction in the inflammatory infiltrate, while CD31/VEGF staining showed improved angiogenesis post-systemic FnAb treatment. These results suggest that systemically administered FnAbs are active within the burn site and can improve healing outcomes. The clinical application of systemically injected Flii monoclonal antibodies could therefore be a potential approach for promoting the healing of large surface area burns immediately after injury.

Keywords: biodistribution, burn, flightless, systemic, fnAbs

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Authors: Getahun Nigusie

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Background; antiretroviral treatment reduce HIV-related morbidity, and prolonged survival of patients however, there is lack of up-to-date information concerning the treatment long term effect on the survival of HIV positive children especially in the study area. Objective: To assess incidence and predictors of mortality among HIV positive children on ART in public hospitals of Harer town who were enrolled from 2011 to 2021. Methodology: Institution based retrospective cohort study was conducted among 429 HIV positive children enrolled in ART clinic from January 1st 2011 to December30th 2021. Data were collected from medical cards by using a data extraction form, Descriptive analyses were used to Summarized the results, and life table was used to estimate survival probability at specific point of time after introduction of ART. Kaplan Meier survival curve together with log rank test was used to compare survival between different categories of covariates, and Multivariate Cox-proportional hazard regression model was used to estimate adjusted Hazard rate. Variables with p-values ≤0.25 in bivariable analysis were candidates to the multivariable analysis. Finally, variables with p-values < 0.05 were considered as significant variables. Results: The study participants had followed for a total of 2549.6 child-years (30596 child months) with an overall mortality rate of 1.5 (95% CI: 1.1, 2.04) per 100 child-years. Their median survival time was 112 months (95% CI: 101–117). There were 38 children with unknown outcome, 39 deaths, and 55 children transfer out to different facility. The overall survival at 6, 12, 24, 48 months were 98%, 96%, 95%, 94% respectively. being in WHO clinical Stage four (AHR=4.55, 95% CI:1.36, 15.24), having anemia(AHR=2.56, 95% CI:1.11, 5.93), baseline low absolute CD4 count (AHR=2.95, 95% CI: 1.22, 7.12), stunting (AHR=4.1, 95% CI: 1.11, 15.42), wasting (AHR=4.93, 95% CI: 1.31, 18.76), poor adherence to treatment (AHR=3.37, 95% CI: 1.25, 9.11), having TB infection at enrollment (AHR=3.26, 95% CI: 1.25, 8.49),and no history of change their regimen(AHR=7.1, 95% CI: 2.74, 18.24), were independent predictors of death. Conclusion: more than half of death occurs within 2 years. Prevalent tuberculosis, anemia, wasting, and stunting nutritional status, socioeconomic factors, and baseline opportunistic infection were independent predictors of death. Increasing early screening and managing those predictors are required.

Keywords: human immunodeficiency virus-positive children, anti-retroviral therapy, survival, Ethiopia

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Authors: Hansraj Bookun, Angela Tan, Rachel Xuan, Linheng Zhao, Kejia Wang, Animesh Singla, David Kim, Christopher Loupos

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Introduction: Incisional wound complications in vascular surgery patients represent a significant clinical and econometric burden of morbidity and mortality. The objective of this study was to trial the feasibility of applying the Prevena negative pressure incision management system as a routine dressing in patients who had undergone arterial surgery. Conventionally, Prevena has been applied to groin incisions, but this study features applications on multiple wound sites such as the thigh or major amputation stumps. Method: This was a cross-sectional observational, single-centre case series of 12 patients who had undergone major vascular surgery. Their wounds were managed with the Prevena system being applied either intra-operatively or on the first post-operative day. Demographic and operative details were collated as well as the length of stay and complication rates. Results: There were 9 males (75%) with mean age of 66 years and the comorbid burden was as follows: ischaemic heart disease (92%), diabetes (42%), hypertension (100%), stage 4 or greater kidney impairment (17%) and current or ex-smoking (83%). The main indications were acute ischaemia (33%), claudication (25%), and gangrene (17%). There were single instances of an occluded popliteal artery aneurysm, diabetic foot infection, and rest pain. The majority of patients (50%) had hybrid operations with iliofemoral endarterectomies, patch arterioplasties, and further peripheral endovascular treatment. There were 4 complex arterial bypass operations and 2 major amputations. The mean length of stay was 17 ± 10 days, with a range of 4 to 35 days. A single complication, in the form of a lymphocoele, was encountered in the context of an iliofemoral endarterectomy and patch arterioplasty. This was managed conservatively. There were no deaths. Discussion: The Prevena wound management system shows that in conjunction with safe vascular surgery, absolute wound complication rates remain low and that it remains a valuable adjunct in the treatment of vasculopaths.

Keywords: wound care, negative pressure, vascular surgery, closed incision

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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: Priyal Chikhaliwala, Sudeshna Chandra

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Liver cancer is one of the most common malignant tumors with poor prognosis. This is because liver cancer does not exhibit any symptoms in early stage of disease. Increased serum level of AFP is clinically considered as a diagnostic marker for liver malignancy. The present diagnostic modalities include various types of immunoassays, radiological studies, and biopsy. However, these tests undergo slow response times, require significant sample volumes, achieve limited sensitivity and ultimately become expensive and burdensome to patients. Considering all these aspects, electrochemical biosensors based on dendrimer-magnetic nanoparticles (MNPs) was designed. Dendrimers are novel nano-sized, three-dimensional molecules with monodispersed structures. Poly-amidoamine (PAMAM) dendrimers with eight –NH₂ groups using ethylenediamine as a core molecule were synthesized using Michael addition reaction. Dendrimers provide added the advantage of not only stabilizing Fe₃O₄ NPs but also displays capability of performing multiple electron redox events and binding multiple biological ligands to its dendritic end-surface. Fe₃O₄ NPs due to its superparamagnetic behavior can be exploited for magneto-separation process. Fe₃O₄ NPs were stabilized with PAMAM dendrimer by in situ co-precipitation method. The surface coating was examined by FT-IR, XRD, VSM, and TGA analysis. Electrochemical behavior and kinetic studies were evaluated using CV which revealed that the dendrimer-Fe₃O₄ NPs can be looked upon as electrochemically active materials. Electrochemical immunosensor was designed by immobilizing anti-AFP onto dendrimer-MNPs by gluteraldehyde conjugation reaction. The bioconjugates were then incubated with AFP antigen. The immunosensor was characterized electrochemically indicating successful immuno-binding events. The binding events were also further studied using magnetic particle imaging (MPI) which is a novel imaging modality in which Fe₃O₄ NPs are used as tracer molecules with positive contrast. Multicolor MPI was able to clearly localize AFP antigen and antibody and its binding successfully. Results demonstrate immense potential in terms of biosensing and enabling MPI of AFP in clinical diagnosis.

Keywords: alpha-fetoprotein, dendrimers, electrochemical biosensors, magnetic nanoparticles

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Authors: D. Maryama AG. Daud, Zuliana Bacho, Stephanie Chok, DG. Mashitah PG. Baharuddin, Mohd Hatta Tarmizi, Nathira Abdul Majeed, Helen Lasimbang

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Lifestyle, physical activity, food intake, genetics and medication are contributing factors for people getting obese. Which in some of the obese people were a low or non-responder to exercise. And obesity is very common clinical feature in women affected by Polycystic Ovarian Syndrome (PCOS). Labisia pumila var. alata (LP) is a local herb which had been widely used by Malay women in treating menstrual irregularities, painful menstruation and postpartum well-being. Therefore, this study was carried out to investigate the effect of LP with a structured exercise program on anthropometric, body composition and physical fitness performance of PCOS patients. By using a single blind and parallel study design, where by subjects were assigned into a 16-wk structured exercise program (3 times a week) interventions; (LP and exercise; LPE, and exercise only; E). All subjects in the LPE group were prescribed 200mg LP; once a day, for 16 weeks. The training heart rate (HR) was monitored based on a percentage of the maximum HR (HRmax) achieved during submaximal exercise test that was conducted at wk-0 and wk-8. The progression of aerobic exercise intensity from 25–30 min at 60 – 65% HRmax during the first week to 45 min at 75–80% HRmax by the end of this study. Anthropometric (body weight, Wt; waist circumference, WC; and hip circumference, HC), body composition (fat mass, FM; percentage body fat, %BF; Fat Free Mass, FFM) and physical fitness performance (push up to failure, PU; 1-minute Sit Up, SU; and aerobic step test, PVO2max) were measured at wk-0, wk-4, wk-8, wk-12, and wk-16. This study found that LP does not have a significant effect on body composition, anthropometric and physical fitness performance of PCOS patients underwent a structured exercise program. It means LP does not improve exercise responses of PCOS patients towards anthropometric, body composition and physical fitness performance. The overall data shows exercise responses of PCOS patients is by increasing their aerobic endurance and muscle endurance performances, there is a significant reduction in FM, PBF, HC, and Wt significantly. Therefore, exercise program for PCOS patients have to focus on aerobic fitness, and muscle endurance.

Keywords: polycystic ovarian syndrome, Labisia pumila var. alata, body composition, aerobic endurance, muscle endurance, anthropometric

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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: Pamela-Zoe Topalli, Niina Junttila, Päivi M. Niemi, Klaus Ranta

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Adolescents’ biased perceptions about their social competence (SC), whether negatively or positively, serve to influence their socioemotional adjustment such as early feelings of social phobia (nowadays referred to as Social Anxiety Disorder-SAD). Despite the importance of biased self-perceptions in adolescents’ psychosocial adjustment, the extent to which discrepancies between self- and others’ evaluations of one’s SC are linked to social phobic symptoms remains unclear in the literature. This study examined the perceptual discrepancy profiles between self- and peers’ as well as between self- and teachers’ evaluations of adolescents’ SC and the interrelations of these profiles with self-reported social phobic symptoms. The participants were 390 3^rd graders (15 years old) of Finnish lower secondary school (50.8% boys, 49.2% girls). In contrast with variable-centered approaches that have mainly been used by previous studies when focusing on this subject, this study used latent profile analysis (LPA), a person-centered approach which can provide information regarding risk profiles by capturing the heterogeneity within a population and classifying individuals into groups. LPA revealed the following five classes of discrepancy profiles: i) extremely negatively biased perceptions of SC, ii) negatively biased perceptions of SC, iii) quite realistic perceptions of SC, iv) positively biased perceptions of SC, and v) extremely positively biased perceptions of SC. Adolescents with extremely negatively biased perceptions and negatively biased perceptions of their own SC reported the highest number of social phobic symptoms. Adolescents with quite realistic, positively biased and extremely positively biased perceptions reported the lowest number of socio-phobic symptoms. The results point out the negatively and the extremely negatively biased perceptions as possible contributors to social phobic symptoms. Moreover, the association of quite realistic perceptions with low number of social phobic symptoms indicates its potential protective power against social phobia. Finally, positively and extremely positively biased perceptions of SC are negatively associated with social phobic symptoms in this study. However, the profile of extremely positively biased perceptions might be linked as well with the existence of externalizing problems such as antisocial behavior (e.g. disruptive impulsivity). The current findings highlight the importance of considering discrepancies between self- and others’ perceptions of one’s SC in clinical and research efforts. Interventions designed to prevent or moderate social phobic symptoms need to take into account individual needs rather than aiming for uniform treatment. Implications and future directions are discussed.

Keywords: adolescence, latent profile analysis, perceptual discrepancies, social competence, social phobia

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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: Chiara Magliacane

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This project aims to analyse the relationship between the post-conflict Northern Irish environment and youth trauma in deprived areas. Using an anthropological perspective and methodology, the study investigates the possible contribution that a socio-cultural perspective can give to the current research on the field, with a special focus on the role of transgenerational trauma. The recognition of the role that socio-economic determinants have on health is usually a challenge for social researchers. In post-conflict Northern Ireland, the overall lack of research about connections between the social context and youth trauma opens the way to the present project. Anthropological studies on social implications of mental disorders have achieved impressive results in many societies; they show how conditions of sufferance and poverty are not intrinsically given, but are the products of historical processes and events. The continuum of violence and the politics of victimhood sustains a culture of silence and fear in deprived areas; this implies the need of investigating the structural and symbolic violence that lies behind the diffusion of mental suffering. The project refers to these concepts from Medical Anthropology and looks at connections between trauma and social, political and economic structures. Accordingly, the study considers factors such as poverty, unemployment, social inequality and gender and class perspectives. At the same time, the project problematises categories such as youth and trauma. 'Trauma' is currently debated within the social sciences since the 'invention' of the Post-Traumatic Stress Disorder (PTSD) in 1980. Current critics made to its clinical conception show how trauma has been mainly analysed as a memory of the past. On the contrary, medical anthropological research focuses on wider perspectives on society and its structures; this is a new and original approach to the study of youth trauma considering that, to author’s best knowledge, there is no research of this kind regarding Northern Ireland. Methods: Qualitative interviews, participant observation. Expected Impact: Local Northern Ireland organizations, i.e. specific charities that provide mental health support. Ongoing and present connections will ensure they will hear about this research.

Keywords: health and social inequalities, Northern Ireland, structural violence, youth

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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: Ozlem Oral, Emre Taskin, Aysel Yuce, Serap Dokmeci, Devrim Gozuacik

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Autophagy is an evolutionary conserved lysosome-dependent catabolic pathway, responsible for the degradation of long-lived proteins, abnormal aggregates and damaged organelles which cannot be degraded by the ubiquitin-proteasome system. Lysosomes degrade the substrates through the activity of lysosomal hydrolases and lysosomal membrane-bound proteins. Mutations in the coding region of these proteins cause malfunctional lysosomes, which contributes to the pathogenesis of lysosomal storage diseases. Gaucher disease is a lysosomal storage disease resulting from the mutation of a lysosomal membrane-associated glycoprotein called glucocerebrosidase and its cofactor saposin C. The disease leads to intracellular accumulation of glucosylceramide and other glycolipids. Because of the essential role of lysosomes in autophagic degradation, Gaucher disease may directly be linked to this pathway. In this study, we investigated the expression of autophagy and/or lysosome-related genes and proteins in fibroblast cells isolated from patients with different mutations. We carried out confocal microscopy analysis and examined autophagic flux by utilizing the differential pH sensitivities of RFP and GFP in mRFP-GFP-LC3 probe. We also evaluated lysosomal pH by active lysosome staining and lysosomal enzyme activity. Beside lysosomes, we also performed proteasomal activity and cell death analysis in patient samples. Our data showed significant attenuation in the expression of key autophagy-related genes and accumulation of their proteins in mutant cells. We found decreased the ability of autophagosomes to fuse with lysosomes, associated with elevated lysosomal pH and reduced lysosomal enzyme activity. Proteasomal degradation and cell death analysis showed reduced proteolytic activity of the proteasome, which consequently leads to increased susceptibility to cell death. Our data indicate that the major degradation pathways are affected by multifunctional lysosomes in mutant patient cells and may underlie in the mechanism of clinical severity of Gaucher patients. (This project is supported by TUBITAK-3501-National Young Researchers Career Development Program, Project No: 112T130).

Keywords: autophagy, Gaucher's disease, glucocerebrosidase, mutant fibroblasts

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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: Maria Medeiros, Suren Surenthiran, Abitha Muralithar, Soushma Seeburuth, Mohammed Mohammed

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Introduction: Appendicitis is the most common surgical emergency globally and can have devastating consequences. Diagnostic imaging in acute appendicitis has become increasingly common in aiding the diagnosis of acute appendicitis. Computerized tomography (CT) and ultrasound (US) are the most commonly used imaging modalities for diagnosing acute appendicitis. Pre-operative imaging has contributed to a reduction of negative appendicectomy rates from between 10-29% to 5%. Literature report CT scan has a diagnostic sensitivity of 94% in acute appendicitis. This clinical audit was conducted to establish if the CT scan's diagnostic yield for acute appendicitis matches the literature. CT scan has a high sensitivity and specificity for diagnosing acute appendicitis and its use can result in a lower negative appendicectomy rate. The aim of this study is to compare the pre-operative imaging findings from CT scans to the histopathology results post-operatively and establish the accuracy of CT scans in aiding the diagnosis of acute appendicitis. Methods: This was a retrospective study focusing on adult presentations to the general surgery department in a district general hospital in central London with an impression of acute appendicitis. We analyzed all patients from July 2022 to December 2022 who underwent a CT scan preceding appendicectomy. Pre-operative CT findings and post-operative histopathology findings were compared to establish the efficacy of CT scans in diagnosing acute appendicitis. Our results were also cross-referenced with pre-existing literature. Data was collected and anonymized using CERNER and analyzed in Microsoft Excel. Exclusion criteria: Children, age <16. Results: 65 patients had CT scans in which the report stated acute appendicitis. Of those 65 patients, 62 patients underwent diagnostic laparoscopies. 100% of patients who underwent an appendicectomy with a pre-operative CT scan showing acute appendicitis had acute appendicitis in histopathology analysis. 3 of the 65 patients who had a CT scan showing appendicitis received conservative treatment. Conclusion: CT scans positive for acute appendicitis had 100% sensitivity and a positive predictive value, which matches published research studies (sensitivity of 94%). The use of CT scans in the diagnostic work-up for acute appendicitis can be extremely helpful in a) confirming the diagnosis and b) reducing the rates of negative appendicectomies and consequently reducing unnecessary operative-associated risks for patients, reducing costs and reducing pressure on emergency theatre lists.

Keywords: acute apendicitis, CT scan, general surgery, imaging

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Authors: Desalegn Feyissa Desu

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Drug therapy problem is a significant challenge to provide high quality health care service for the patients. It is associated with morbidity, mortality, increased hospital stay, and reduced quality of life. Moreover, pediatric patients are quite susceptible to drug therapy problems. Thus this study aimed to assess drug therapy problem and its contributing factors among pediatric patients diagnosed with infectious disease admitted to pediatric ward of Jimma university medical center, from April 1 to June 30, 2018. Prospective observational study was conducted among pediatric patients with infectious disease admitted from April 01 to June 30, 2018. Drug therapy problems were identified by using Cipolle’s and strand’s drug related problem classification method. Patient’s written informed consent was obtained after explaining the purpose of the study. Patient’s specific data were collected using structured questionnaire. Data were entered into Epi data version 4.0.2 and then exported to statistical software package version 21.0 for analysis. To identify predictors of drug therapy problems occurrence, multiple stepwise backward logistic regression analysis was done. The 95% CI was used to show the accuracy of data analysis and statistical significance was considered at p-value < 0.05. A total of 304 pediatric patients were included in the study. Of these, 226(74.3%) patients had at least one drug therapy problem during their hospital stay. A total of 356 drug therapy problems were identified among two hundred twenty six patients. Non-compliance (28.65%) and dose too low (27.53%) were the most common type of drug related problems while disease comorbidity [AOR=3.39, 95% CI= (1.89-6.08)], Polypharmacy [AOR=3.16, 95% CI= (1.61-6.20)] and more than six days stay in hospital [AOR=3.37, 95% CI= (1.71-6.64) were independent predictors of drug therapy problem occurrence. Drug therapy problems were common in pediatric patients with infectious disease in the study area. Presence of comorbidity, polypharmacy and prolonged hospital stay were the predictors of drug therapy problem in study area. Therefore, to overcome the significant gaps in pediatric pharmaceutical care, clinical pharmacists, Pediatricians, and other health care professionals have to work in collaboration.

Keywords: drug therapy problem, pediatric, infectious disease, Ethiopia

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Authors: Frank Fan

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PharmD (Doctor of Pharmacy) education has confronted an increasing challenge — curricular overload, a phenomenon resulting from the expansion of curricular requirements, as PharmD education strives to produce graduates who are practice-ready. The aftermath of the global pandemic has amplified the need for healthcare professionals, leading to a growing trend of assigning more responsibilities to them to address the global healthcare shortage. For instance, the pharmacist’s role has expanded to include not only compounding and distributing medication but also providing clinical services, including minor ailments management, patient counselling and vaccination. Consequently, PharmD programs have responded by continually expanding their curricula adding more requirements. While these changes aim to enhance the education and training of future professionals, they have also led to unintended consequences, including curricular overload, student burnout, and a potential decrease in program quality. To address the issue and ensure program quality, there is a growing need for evidence-based curriculum reforms. My research seeks to integrate Cognitive Load Theory, emerging machine learning algorithms within artificial intelligence (AI), and statistical approaches to develop a quantitative framework for optimizing curriculum design within the PharmD program at the University of Toronto, the largest PharmD program within Canada, to provide quantification and measurement of issues that currently are only discussed in terms of anecdote rather than data. This research will serve as a guide for curriculum planners, administrators, and educators, aiding in the comprehension of how the pharmacy degree program compares to others within and beyond the field of pharmacy. It will also shed light on opportunities to reduce the curricular load while maintaining its quality and rigor. Given that pharmacists constitute the third-largest healthcare workforce, their education shares similarities and challenges with other health education programs. Therefore, my evidence-based, data-driven curriculum analysis framework holds significant potential for training programs in other healthcare professions, including medicine, nursing, and physiotherapy.

Keywords: curriculum, curriculum analysis, health professions education, reflective writing, machine learning

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

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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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Authors: Heba A. Hazzah, Ragwa M. Farid, Maha M. A. Nasra, Mennatallah Zakria, Magda A. El Massik, Ossama Y. Abdallah

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Introduction: Curcumin (Cur) is a polyphenol derived from the herbal remedy and dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties following oral or topical administration. The buccal delivery of curcumin can be useful for both systemic and local disease treatments such as gingivitis, periodontal diseases, oral carcinomas, and precancerous oral lesions. Despite of its high activity, it suffers a limited application due to its low oral bioavailability, poor aqueous solubility, and instability. Aim: Preparation and characterization of curcumin solid lipid nanoparticles with a high loading capacity into a mucoadhesive gel for buccal application. Methodology: Curcumin was formulated as nanoparticles using different lipids, namely Gelucire 39/01, Gelucire 50/13, Precirol, Compritol, and Polaxomer 407 as a surfactant. The SLN were dispersed in a mucoadhesive gel matrix to be applied to the buccal mucosa. All formulations were evaluated for their content, entrapment efficiency, particle size, in vitro drug dialysis, ex vivo mucoadhesion test, and ex vivo permeation study using chicken buccal mucosa. Clinical evaluation was conducted on 15 cases suffering oral erythroplakia and erosive lichen planus. Results: The results showed high entrapment efficiency reaching almost 90 % using Gelucire 50, the loaded gel with Cur-SLN showed good adhesion property and 25 minutes in vivo residence time. In addition to stability enhancement for the Cur powder. All formulae did not show any drug permeated however, a significant amount of Cur was retained within the mucosal tissue. Pain and lesion sizes were significantly reduced upon topical treatment. Complete healing was observed after 6 weeks of treatment. Conclusion: These results open a room for the pharmaceutical technology to optimize the use of this golden magical powder to get the best out of it. In addition, the lack of local anti-inflammatory compounds with reduced side effects intensifies the importance of studying natural products for this purpose.

Keywords: curcumin, erythroplakia, mucoadhesive, pain, solid lipid nanoparticles

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Authors: Meredith Rossi, Lesley Lee, Mary Wear, Mary Van Baalen, Bradley Rhodes

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The astronaut community is unique, and may be disproportionately exposed to occupational hazards not commonly seen in other communities. The extent to which the demands of the astronaut occupation and exposure to spaceflight-related hazards affect the health of the astronaut population over the life course is not completely known. A better understanding of the individual, population, and mission impacts of astronaut occupational exposures is critical to providing clinical care, targeting occupational surveillance efforts, and planning for future space exploration. The ability to characterize the risk of latent health conditions is a significant component of this understanding. Provision of health screening services to active and former astronauts ensures individual, mission, and community health and safety. Currently, the NASA-Johnson Space Center (JSC) Flight Medicine Clinic (FMC) provides extensive medical monitoring to active astronauts throughout their careers. Upon retirement, astronauts may voluntarily return to the JSC FMC for an annual preventive exam. However, current retiree monitoring includes only selected screening tests, representing an opportunity for augmentation. The potential long-term health effects of spaceflight demand an expanded framework of testing for former astronauts. The need is two-fold: screening tests widely recommended for other aging populations are necessary to rule out conditions resulting from the natural aging process (e.g., colonoscopy, mammography); and expanded monitoring will increase NASA’s ability to better characterize conditions resulting from astronaut occupational exposures. To meet this need, NASA has begun an extensive exploration of the overall approach, cost, and policy implications of expanding the medical monitoring of former NASA astronauts under the Astronaut Occupational Health program. Increasing the breadth of monitoring services will ultimately enrich the existing evidence base of occupational health risks to astronauts. Such an expansion would therefore improve the understanding of the health of the astronaut population as a whole, and the ability to identify, mitigate, and manage such risks in preparation for deep space exploration missions.

Keywords: astronaut, long-term health, NASA, occupational health, surveillance

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Authors: Mario Sandro F. Rocha, Carlos S. Ande, Anderson A. Oliveira, Felipe M. Bersotti, Lucas O. Venzel

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The inertial motion capture systems (mocap) are among the most suitable tools for quantitative clinical analysis in rehabilitation and sports medicine. The inertial measuring units (IMUs), composed by accelerometers, gyroscopes, and magnetometers, are able to measure spatial orientations and calculate displacements with sufficient precision for applications in biomechanical analysis of movement. Furthermore, this type of system is relatively affordable and has the advantages of portability and independence from external references. In this work, we present the last version of our inertial motion capture system, based on the foregoing technology, with a unity interface designed for rehabilitation and sports. In our hardware architecture, only one serial port is required. First, the board client must be connected to the computer by a USB cable. Next, an available serial port is configured and opened to establish the communication between the client and the application, and then the client starts scanning for the active MOCAP_S servers around. The servers play the role of the inertial measuring units that capture the movements of the body and send the data to the client, which in turn create a package composed by the ID of the server, the current timestamp, and the motion capture data defined in the client pre-configuration of the capture session. In the current version, we can measure the game rotation vector (grv) and linear acceleration (lacc), and we also have a step detector that can be abled or disabled. The grv data are processed and directly linked to the bones of the 3D model, and, along with the data of lacc and step detector, they are also used to perform the calculations of displacements and other variables shown on the graphical user interface. Our user interface was designed to calculate and present variables that are important for rehabilitation and sports, such as cadence, speed, total gait cycle, gait cycle length, obliquity and rotation, and center of gravity displacement. Our goal is to present a low-cost portable and wearable system with a friendly interface for application in biomechanics and sports, which also performs as a product of high precision and low consumption of energy.

Keywords: biomechanics, inertial sensors, motion capture, rehabilitation

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Authors: G. A. Khalid, R. Prabhu, W. Whittington, M. D. Jones

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To establish a causal relationship of infant head injury consequences, this present study addresses the necessary challenges of cranial geometry and the physical response complexities of the paediatric head tissues. Herein, we describe a new approach to characterising and understanding infant head impact mechanics by developing printed head models, using high resolution clinical postmortem imaging, to provide the most complete anatomical representation currently available, and biological material response data-matched polypropylene polymers, to replicate the relative mechanical response properties of immature cranial bone, sutures and fontanelles. Additive manufacturing technology was applied to creating a physical polymeric model of a newborn infant skull, using PolyJet printed materials. Infant skull materials responses, were matched by a response characterisation study, utilising uniaxial tensile testing (1 mm min-1 loading rate), to determine: the stiffness, ultimate tensile strength and maximum strain of rigid and rubber additively manufactured acrylates. The results from the mechanical experiments confirm that the polymeric materials RGD835 Vero White Plus (White), representing the frontal and parietal bones; RGD8510- DM Rigid Light Grey25 (Grey), representing the occipital bone; and FLX9870-DM (Black) representing the suture and fontanelles, were found to show a close stiffness -correlation (E) at ambient temperatures. A 3D physical model of infant head was subsequently printed from the matched materials and subsequently validated against results obtained from a series of Post Mortem Human Surrogate (PMHS) tests. A close correlation was demonstrated between the model impact tests and the PMHS. This study, therefore, represents a key step towards applying printed physical models to understanding head injury biomechanics and is useful in the efforts to predict and mitigate head injury consequences in infants, whether accidental or by abuse.

Keywords: infant head trauma, infant skull, material response, post mortem human subjects, polyJet printing

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Authors: Dalma Dojcsák, Csaba Váradi, Flóra Farkas, Tamás Farkas, János Papp, Béla Viskolcz

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Background: Appendicitis is a common acute inflammatory condition in both children and adults, but current laboratory markers such as C-reactive protein (CRP), white blood cell count (WBC), absolute neutrophil count (ANC), and red blood cell count (RNC) lack specificity in detecting appendicitis-related inflammation. N-glycosylation, an asparagine-linked glycosylation process, plays a vital role in cellular interactions, angiogenesis, immune response, and effector functions. Altered N-glycosylation impacts tumor growth and both acute and chronic inflammatory processes. IgG, the second most abundant glycoprotein in serum, shows altered glycosylation patterns during inflammation, suggesting that IgG glycan modifications may serve as potential biomarkers for appendicitis. Specifically, increased levels of agalactosylated IgG glycans are a known feature of various inflammatory conditions, potentially including appendicitis. Identifying pediatric appendicitis remains challenging due to the absence of specific biomarkers, which makes diagnosis reliant on clinical symptoms, imaging such as ultrasound, and nonspecific lab indicators (e.g., CRP, WBC, ANC). In this study, we analyzed the IgG derived N-glycome in pediatric patients with appendicitis compared with healthy controls. Methodology: The N-glycome was analyzed by high-performance liquid-chromatography combined with mass spectrometry. IgG was isolated from serum samples by Protein G column. The IgG derived glycans were released by enzymatic deglycosylation and fluorescent tags were attached to each glycan moiety, which made necessitates the sample clean-up for further reliable quantitation. Overall, 38 controls and 40 serum samples diagnosed with pediatric appendicitis were analyzed by HILIC-MS methods. Multivariate statistical tests were performed with area percentage under the peak data derived from the integrated peaks, which were obtained from the chromatograms. Conclusions: Our results represented the altered N-glycome of IgG in pediatric appendicitis is similar with other observations. The glycosylation pattern reported so far for IgG is characterized by decreased galactosylation and sialylation, and an increase in fucosylation.

Keywords: N-glycosylation, liquid chromatography, mass spectrometry, inflammation, appendicitis, immunoglobulin G

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