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Authors: Kantha Siddhanth Gujjari, Shaani Singhal, Robert Andrew Danks, Adrian Praeger

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Background: Trigeminal neuralgia (TN) is a heterogenous pain syndrome characterised by short paroxysms of lancinating facial pain in the distribution of the trigeminal nerve, often triggered by usually innocuous stimuli. TN has a low prevalence of less than 0.1%, of which 80% to 90% is caused by compression of the trigeminal nerve from an adjacent artery or vein. The root entry zone of the trigeminal nerve is most sensitive to neurovascular conflict (NVC), causing dysmyelination. Whilst microvascular decompression (MVD) is an effective treatment for TN with NVC, all patients do not achieve long-term pain relief. Pre-operative scoring systems by Panczykowski and Hardaway have been proposed but have not been externally validated. These pre-operative scoring systems are composite scores calculated according to a subtype of TN, presence and degree of neurovascular conflict, and response to medical treatments. There is discordance in the assessment of NVC identified on pre-operative magnetic resonance imaging (MRI) between neurosurgeons and radiologists. To our best knowledge, the prognostic impact for MVD of this difference of interpretation has not previously been investigated in the form of a composite scoring system such as those suggested by Panczykowski and Hardaway. Aims: This study aims to identify prognostic factors and externally validate the proposed scoring systems by Panczykowski and Hardaway for TN. A secondary aim is to investigate the prognostic difference between a neurosurgeon's interpretation of NVC on MRI compared with a radiologist’s. Methods: This retrospective cohort study included 95 patients who underwent de novo MVD in a single neurosurgical unit in Melbourne. Data was recorded from patients’ hospital records and neurosurgeon’s correspondence from perioperative clinic reviews. Patient demographics, type of TN, distribution of TN, response to carbamazepine, neurosurgeon, and radiologist interpretation of NVC on MRI, were clearly described prospectively and preoperatively in the correspondence. Scoring systems published by Panczykowski et al. and Hardaway et al. were used to determine composite scores, which were compared with the recurrence of TN recorded during follow-up over 1-year. Categorical data analysed using Pearson chi-square testing. Independent numerical and nominal data analysed with logistical regression. Results: Logistical regression showed that a Panczykowski composite score of greater than 3 points was associated with a higher likelihood of pain-free outcome 1-year post-MVD with an OR 1.81 (95%CI 1.41-2.61, p=0.032). The composite score using neurosurgeon’s impression of NVC had an OR 2.96 (95%CI 2.28-3.31, p=0.048). A Hardaway composite score of greater than 2 points was associated with a higher likelihood of pain-free outcome 1 year post-MVD with an OR 3.41 (95%CI 2.58-4.37, p=0.028). The composite score using neurosurgeon’s impression of NVC had an OR 3.96 (95%CI 3.01-4.65, p=0.042). Conclusion: Composite scores developed by Panczykowski and Hardaway were validated for the prediction of response to MVD in TN. A composite score based on the neurosurgeon’s interpretation of NVC on MRI, when compared with the radiologist’s had a greater correlation with pain-free outcomes 1 year post-MVD.

Keywords: de novo microvascular decompression, neurovascular conflict, prognosis, trigeminal neuralgia

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Authors: Ammar Asma, Bouafia Nabiha, Dhahri Meriem, Ben Cheikh Asma, Ezzi Olfa, Chafai Rim, Njah Mansour

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Despite recent advances in treatment of the lung cancer patients, the prognosis remains poor. Information is limited regarding health related quality of life (QOL) status of advanced lung cancer patients. The purposes of this study were: to assess patient reported symptom burden, to measure their QOL, and to identify determinant factors associated with QOL. Materials/Methods: A cross sectional study of 60 patients was carried out from over the period of 03 months from February 1st to 30 April 2016. Patients were recruited in two department of health care: Pneumology department in a university hospital in Sousse and an oncology unit in a University Hospital in Kairouan. Patients with advanced stage (III and IV) of lung cancer who were hospitalized or admitted in the day hospital were recruited by convenience sampling. We used a questionnaire administrated and completed by a trained interviewer. This questionnaire is composed of three parts: demographic, clinical and therapeutic information’s, QOL measurements: based on the SF-36 questionnaire, Symptom’s burden measurement using the Lung Cancer Symptom Scale (LCSS). To assess Correlation between symptoms burden and QOL, we compared the scores of two scales two by two using the Pearson correlation. To identify factors influencing QOL in Lung cancer, a univariate statistical analysis then, a stepwise backward approach, wherein the variables with p< 0.2, were carried out to determine the association between SF-36 scores and different variables. Results: During the study period, 60 patients consented to complete symptom and quality of life questionnaires at a single point time (72% were recruited from day hospital). The majority of patients were male (88%), age ranged from 21 to 79 years with a mean of 60.5 years. Among patients, 48 (80%) were diagnosed as having non-small cell lung carcinoma (NSCLC). Approximately, 60 % (n=36) of patients were in stage IV, 25 % in stage IIIa and 15 % in stage IIIb. For symptom burden, the symptom burden index was 43.07 (Standard Deviation, 21.45). Loss of appetite and fatigue were rated as the most severe symptoms with mean scores (SD): 49.6 (25.7) and 58.2 (15.5). The average overall score of SF36 was 39.3 (SD, 15.4). The physical and emotional limitations had the lowest scores. Univariate analysis showed that factors which influence negatively QOL were: married status (p<0.03), smoking cessation after diagnosis (p<0.024), LCSS total score (p<0.001), LCSS symptom burden index (p<0.001), fatigue (p<0.001), loss of appetite (p<0.001), dyspnea (p<0.001), pain (p<0.002), and metastatic stage (p<0.01). In multivariate analysis, unemployment (p<0.014), smoking cessation after diagnosis (p<0.013), consumption of analgesic (p<0.002) and the indication of an analgesic radiotherapy (p<0.001) are revealed as independent determinants of QOL. The result of the correlation analyses between total LCSS scores and the total and individual domain SF36 scores was significant (p<0.001); the higher total LCSS score is, the poorer QOL is. Conclusion: A built in support of lung cancer patients would better control the symptoms and promote the QOL of these patients.

Keywords: quality of life, lung cancer, metastasis, symptoms burden

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Authors: Samuel Sii, David Homewood, Brendan Dittmer, Tony Nzembela, Jonathan O’Brien, Niall Corcoran, Dinesh Agarwal

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Introduction: Innovation is key to the advancement of medicine and improvement in patient care. This is particularly true in surgery, where pioneering techniques have transformed operative management from a historically highly risky peri-morbid and disfiguring to the contemporary low-risk, sterile and minimally invasive treatment modality. There is a delicate balance between enabling innovation and minimizing patient harm. Publication and discussion of novel surgical techniques allow for independent expert review. Recent journals have increasingly stringent requirements for publications and often require larger case volumes for novel techniques to be published. This potentially impairs the initial publication of novel techniques and slows innovation. The historical perspective provides a better understanding of how requirements for the publication of new techniques have evolved over time. This is essential in overcoming challenges in developing novel techniques. Aims and Objectives: We explore how novel techniques in Urology have been published over the past 200 years. Our objective is to describe the trend and publication requirements of novel urological techniques, both historical and present. Methods: We assessed all major urological operations using multipronged historical analysis. An initial literature search was carried out through PubMed and Google Scholar for original literature descriptions, followed by reference tracing. The first publication of each pioneering urological procedure was recorded. Data collected includes the year of publication, description of the procedure, number of cases and outcomes. Results: 65 papers describing pioneering techniques in Urology were identified. These comprised of 2 experimental studies, 17 case reports and 46 case series. These papers described various pioneering urological techniques in urological oncology, reconstructive urology and endourology. We found that, historically, techniques were published with smaller case numbers. Often, the surgical technique itself was a greater focus of the publication than patient outcome data. These techniques were often adopted prior to larger publications. In contrast, the risks and benefits of recent novel techniques are often well-defined prior to adoption. This historical perspective is important as recent journals have requirements for larger case series and data outcomes. This potentially impairs the initial publication of novel techniques and slows innovation. Conclusion: A better understanding of historical publications and their effect on the adoption of urological techniques into common practice could assist the current generation of Urologists in formulating a safe, efficacious process in promoting surgical innovation and the development of novel surgical techniques. We propose the reassessment of requirements for the publication of novel operative techniques by splitting technical perspectives and data-orientated case series. Existing frameworks such as IDEAL and ASERNIP-S should be integrated into current processes when investigating and developing new surgical techniques to ensure efficacious and safe innovation within surgery is encouraged.

Keywords: urology, surgical innovation, novel surgical techniques, publications

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Authors: Reshu Yadav, Himanshu Joshi, S. K. Tripathi

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Fresh water is a scarce resource which is essential for humans and ecosystems, but its distribution is uneven. Agricultural production accounts for 70% of all surface water supplies. It is projected that against the expansion in the area equipped for irrigation by 0.6% per year, the global potential irrigation water demand would rise by 9.5% during 2021-25. This would, on one hand, have to compete against the sharply rising urban water demand. On the other, it would also have to face the fear of climate change, as temperatures rise and crop yields could drop from 10-30% in many large areas. The huge demand for irrigation combined with fresh water scarcity encourages to explore the reuse of wastewater as a resource. However, the use of such wastewater is often linked to the safety issues when used non judiciously or with poor safeguards while irrigating food crops. Paddy is one of the major crops globally and amongst the most important in South Asia and Africa. In many parts of the world, use of municipal wastewater has been promoted as a viable option in this regard. In developing and fast growing countries like India, regularly increasing wastewater generation rates may allow this option to be considered quite seriously. In view of this, a pilot field study was conducted at the Jagjeetpur Municipal Sewage treatment plant situated in the Haridwar town of Uttarakhand state, India. The objectives of the present study were to study the effect of treated wastewater on the production of various paddy varieties (Sharbati, PR-114, PB-1, Menaka, PB1121 and PB 1509) and emission of GHG gases (CO2, CH4 and N2O) as compared to the same varieties grown in the control plots irrigated with fresh water. Of late, the concept of water footprint assessment has emerged, which explains enumeration of various types of water footprints of an agricultural entity from its production to processing stages. Paddy, the most water demanding staple crop of Uttarakhand state, displayed a high green water footprint value of 2966.538 m3/ton. Most of the wastewater irrigated varieties displayed upto 6% increase in production, except Menaka and PB-1121, which showed a reduction in production (6% and 3% respectively), due to pest and insect infestation. The treated wastewater was observed to be rich in Nitrogen (55.94 mg/ml Nitrate), Phosphorus (54.24 mg/ml) and Potassium (9.78 mg/ml), thus rejuvenating the soil quality and not requiring any external nutritional supplements. Percentage increase of GHG gases on irrigation with treated municipal waste water as compared to control plots was observed as 0.4% - 8.6% (CH4), 1.1% - 9.2% (CO2), and 0.07% - 5.8% (N2O). The variety, Sharbati, displayed maximum production (5.5 ton/ha) and emerged as the most resistant variety against pests and insects. The emission values of CH4 ,CO2 and N2O were 729.31 mg/m2/d, 322.10 mg/m2/d and 400.21 mg/m2/d in water stagnant condition. This study highlighted a successful possibility of reuse of wastewater for non-potable purposes offering the potential for exploiting this resource that can replace or reduce existing use of fresh water sources in agricultural sector.

Keywords: greenhouse gases, nutrients, water footprint, wastewater irrigation

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Authors: Modi Alsubaie, Chris Dickens, Barnaby Dunn, Andy Gibson, Obioha Ukoumunned, Alison Evans, Rachael Vicary, Manish Gandhi, Willem Kuyken

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Background: Depression co-occurs in 20% of people with cardiovascular disorders, can persist for years and predicts worse physical health outcomes. While psychosocial treatments have been shown to effectively treat acute depression in those with comorbid cardiovascular disorders, to date there has been no evaluation of approaches aiming to prevent relapse and treat residual depression symptoms in this group. Therefore, the current study aimed to examine the feasibility and acceptability of a randomised controlled trial design evaluating an adapted version of mindfulness-based cognitive therapy (MBCT) designed specifically for people with co-morbid depression and cardiovascular disorders. Methods: A 3-arm feasibility randomised controlled trial was conducted, comparing MBCT adapted for people with cardiovascular disorders plus treatment as usual (TAU), mindfulness-based stress reduction (MBSR) plus TAU, and TAU alone. Participants completed a set of self-report measures of depression severity, anxiety, quality of life, illness perceptions, mindfulness, self-compassion and affect and had their blood pressure taken immediately before, immediately after, and three months following the intervention. Those in the adapted-MBCT arm additionally underwent a qualitative interview to gather their views about the adapted intervention. Results: 3400 potentially eligible participants were approached when attending an outpatient appointment at a cardiology clinic or via a GP letter following a case note search. 242 (7.1%) were interested in taking part, 59 (1.7%) were screened as being suitable, and 33 (<1%) were eventually randomised to the three groups. The sample was heterogeneous in terms of whether they reported current depression or had a history of depression and the time since the onset of cardiovascular disease (one to 25 years). Of 11 participants randomised to adapted MBCT seven completed the full course, levels of home mindfulness practice were high, and positive qualitative feedback about the intervention was given. Twenty-nine out of 33 participants randomised completed all the assessment measures at all three-time points. With regards to the primary outcome (depression), five out of the seven people who completed the adapted MBCT and three out of five under MBSR showed significant clinical change, while in TAU no one showed any clinical change at the three-month follow-up. Conclusions: The adapted MBCT intervention was feasible and acceptable to participants. However, aspects of the trial design were not feasible. In particular, low recruitment rates were achieved, and there was a high withdrawal rate between screening and randomisation. Moreover, the heterogeneity in the sample was high meaning the adapted intervention was unlikely to be well tailored to all participants needs. This suggests that if the decision is made to move to a definitive trial, study recruitment procedures will need to be revised to more successfully recruit a target sample that optimally matches the adapted intervention.

Keywords: mindfulness-based cognitive therapy (MBCT), depression, cardiovascular disorders, feasibility, acceptability

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Authors: Chia-Yi Wu, Jung-Chen Chang, Wen-Yu Hu, Ming-Been Lee

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In nearly all physical health conditions, suicide risk is increased compared to healthy people even after adjustment for age, gender, mental health, and substance use diagnoses. In order to highlight the importance of suicide risk assessment for the inpatients and early identification and engagement for inpatients’ mental health problems, a study was designed aiming at developing a comprehensive psychosomatic nursing engagement (PSNE) model with standardized operation procedures informing how nurses communicate, assess, and engage with the inpatients with emotional distress. The purpose of the study was to promote the gatekeeping role of clinical nurses in performing brief assessment and interventions to detect depression and anxiety symptoms among the inpatients, particularly in non-psychiatric wards. The study will be carried out in a 2000-bed university hospital in Northern Taiwan in 2019. We will select a ward for trial and develop feasible procedures and in-job training course for the nurses to offer mental health care, which will also be validated through professional consensus meeting. The significance of the study includes the following three points: (1) The study targets at an important but less-researched area of PSNE model in the cultural background of Taiwan, where hospital service is highly accessible, but mental health and suicide risk assessment are hardly provided by non-psychiatric healthcare personnel. (2) The issue of PSNE could be efficient and cost-effective in the identification of suicide risks at an early stage to prevent inpatient suicide or to reduce future suicide risk by early treatment of mental illnesses among the high-risk group of hospitalized patients who are more than three-times lethal to suicide. (3) Utilizing a brief tool with its established APP ('The Five-item Brief Symptom Rating Scale, BSRS-5'), we will invent the standardized procedure of PSNE and referral steps in collaboration with the medical teams across the study hospital. New technological tools nested within nursing assessment/intervention will concurrently be invented to facilitate better care quality. The major outcome measurements will include tools for early identification of common mental distress and suicide risks, i.e., the BSRS-5, revised BSRS-5, and the 9-item Concise Mental Health Checklist (CMHC-9). The main purpose of using the CMHC-9 in clinical suicide risk assessment is mainly to provide care and build-up therapeutic relationship with the client, so it will also be used to nursing training highlighting the skills of supportive care. Through early identification of the inpatients’ depressive symptoms or other mental health care needs such as insomnia, anxiety, or suicide risk, the majority of the nursing clinicians would be able to engage in critical interventions that alleviate the inpatients’ suffering from mental health problems, given a feasible nursing input.

Keywords: mental health care, clinical outcome improvement, clinical nurses, suicide prevention, psychosomatic nursing

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Authors: Karen L. Rincon-Granados, América R. Vázquez-Olmos, Adriana-Patricia Rodríguez-Hernández, Gina Prado-Prone, Margarita Rivera, Roberto Y. Sato-Berrú

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In this work, a hybrid film based on poly-3-hydroxybutyrate (P3HB) and nickel ferrite (NiFe₂O₄) nanoparticles (NPs) was obtained by a simple and reproducible methodology in order to study its antibacterial and cytotoxic properties. The motivation for this research is the current antimicrobial resistance (RAM). This is a threat to human health and development worldwide. RAM is caused by the emergence of bacterial strains resistant to traditional antibiotics that were used as treatment. Due to this, the need to investigate new alternatives for preventing and treating bacterial infections emerges. In this sense, metal oxide NPs have aroused great interest due to their unique physicochemical properties. However, their use is limited by the nanostructured nature, commonly obtained by chemical and physical synthesis methods, as powders or colloidal dispersions. Therefore, the incorporation of nanostructured materials in polymer matrices to obtain hybrid materials that allow disinfecting and preventing the spread of bacteria on various surfaces. Accordingly, this work presents the synthesis and study of the antibacterial properties of the P3HB@NiFe₂O₄ hybrid film as a potential material to inhibit bacterial growth. The NiFe₂O₄ NPs were previously synthesized by a mechanochemical method. The P3HB and P3HB@NiFe₂O₄ films were obtained by the solvent casting method. The films were characterized by X-ray diffraction (XRD), Raman scattering, and scanning electron microscopy (SEM). The XRD pattern showed that the NiFe₂O₄ NPs were incorporated into the P3HB polymer matrix and retained their nanometric sizes. By energy dispersive X-ray spectroscopy (EDS), it was observed that the NPs are homogeneously distributed in the film. The bactericidal effect of the films obtained was evaluated in vitro using the broth surface method against two opportunistic and nosocomial pathogens, Staphylococcus aureus and Pseudomonas aeruginosa. The bacterial growth results showed that the P3HB@NiFe₂O₄ hybrid film was inhibited by 97% and 96% for S. aureus and P. aeruginosa, respectively. Surprisingly, the P3HB film inhibited both bacterial strains by around 90%. The cytotoxicity of the NiFe₂O₄ NPs, P3HB@NiFe₂O₄ hybrid film, and the P3HB film was evaluated using human skin cells, keratinocytes, and fibroblasts, finding that the NPs are biocompatible. The P3HB film and hybrids are cytotoxic, which demonstrated that although P3HB is known and reported as a biocompatible polymer, under our work conditions, P3HB was cytotoxic. Its bactericidal effect could be related to this activity. Its films are bactericidal and cytotoxic to keratinocytes and fibroblasts, the first barrier of human skin. Despite this, the hybrid film of P3HB@NiFe₂O₄ presents synergy with the bactericidal effect between P3HB and NPs, increasing bacterial inhibition. In addition, NPs decrease the cytotoxicity of P3HB to keratinocytes. The methodology used in this work was successful in producing hybrid films with antibacterial activity. However, future challenges are generated to find relationships between NPs and P3HB that allow taking advantage of their bactericidal properties and do not compromise biocompatibility.

Keywords: poly-3-hydroxybutyrate, nanoparticles, hybrid film, antibacterial

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Authors: Langhit Kurar, Loren Charles

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Introduction: In light of recent BOAST 12 (August 2016) published guidance on management of ankle fractures, the project aimed to highlight key discrepancies throughout the care trajectory from admission to point of discharge at a district general hospital. Wide breadth of data covering three key domains: accident and emergency, radiology, and orthopaedic surgery were subsequently stratified and recommendations on note documentation, and outpatient follow up were made. Methods: A retrospective twelve month audit was conducted reviewing results of ankle fracture management in 37 patients. Inclusion criterion involved all patients seen at Darent Valley Hospital (DVH) emergency department with radiographic evidence of an ankle fracture. Exclusion criterion involved all patients managed solely by nursing staff or having sustained purely ligamentous injury. Medical notes, including discharge summaries and the PACS online radiographic tool were used for data extraction. Results: Cross-examination of the A & E domain revealed limited awareness of the BOAST 12 recent publication including requirements to document skin integrity and neurovascular assessment. This had direct implications as this would have changed the surgical plan for acutely compromised patients. The majority of results obtained from the radiographic domain were satisfactory with appropriate X-rays taken in over 95% of cases. However, due to time pressures within A & E, patients were often left without a post manipulation XRAY in a backslab. Poorly reduced fractures were subsequently left for a long period resulting in swollen ankles and a time-dependent lag to surgical intervention. This had knocked on implications for prolonged inpatient stay resulting in hospital-acquired co-morbidity including pressure sores. Discussion: The audit has highlighted several areas of improvement throughout the disease trajectory from review in the emergency department to follow up as an outpatient. This has prompted the creation of an algorithm to ensure patients with significant fractures presenting to the emergency department are seen promptly and treatment expedited as per recent guidance. This includes timing for X-rays taken in A & E. Re-audit has shown significant improvement in both documentation at time of presentation and appropriate follow-up strategies. Within the orthopedic domain, we are in the process of creating an ankle fracture pathway to ensure imaging and weight bearing status are made clear to the consulting clinicians in an outpatient setting. Significance/Clinical Relevance: As a result of the ankle fracture algorithm we have adapted the BOAST 12 guidance to shape an intrinsic pathway to not only improve patient management within the emergency department but also create a standardised format for follow up.

Keywords: ankle, fracture, BOAST, radiology

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Authors: Ashok Kumar, Shiv Brat Singh, Kalyan Kumar Ray

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There is growing awareness to design steels against fatigue damage Ferrite martensite dual-phase steels are known to exhibit favourable mechanical properties like good strength, ductility, toughness, continuous yielding, and high work hardening rate. However, dual-phase steels containing bainite as second phase are potential alternatives for ferrite martensite steels for certain applications where good fatigue property is required. Fatigue properties of dual phase steels are popularly assessed by the nature of variation of crack growth rate (da/dN) with stress intensity factor range (∆K), and the magnitude of fatigue threshold (∆Kth) for long cracks. There exists an increased emphasis to understand not only the long crack fatigue behavior but also short crack growth behavior of ferrite bainite dual phase steels. The major objective of this report is to examine the influence of microstructures on the short and long crack growth behavior of a series of developed dual-phase steels with varying amounts of bainite and. Three low carbon steels containing Nb, Cr and Mo as microalloying elements steels were selected for making ferrite-bainite dual-phase microstructures by suitable heat treatments. The heat treatment consisted of austenitizing the steel at 1100°C for 20 min, cooling at different rates in air prior to soaking these in a salt bath at 500°C for one hour, and finally quenching in water. Tensile tests were carried out on 25 mm gauge length specimens with 5 mm diameter using nominal strain rate 0.6x10⁻³ s⁻¹ at room temperature. Fatigue crack growth studies were made on a recently developed specimen configuration using a rotating bending machine. The crack growth was monitored by interrupting the test and observing the specimens under an optical microscope connected to an Image analyzer. The estimated crack lengths (a) at varying number of cycles (N) in different fatigue experiments were analyzed to obtain log da/dN vs. log °∆K curves for determining ∆Kthsc. The microstructural features of these steels have been characterized and their influence on the near threshold crack growth has been examined. This investigation, in brief, involves (i) the estimation of ∆Kthsc and (ii) the examination of the influence of microstructure on short and long crack fatigue threshold. The maximum fatigue threshold values obtained from short crack growth experiments on various specimens of dual-phase steels containing different amounts of bainite are found to increase with increasing bainite content in all the investigated steels. The variations of fatigue behavior of the selected steel samples have been explained with the consideration of varying amounts of the constituent phases and their interactions with the generated microstructures during cyclic loading. Quantitative estimation of the different types of fatigue crack paths indicates that the propensity of a crack to pass through the interfaces depends on the relative amount of the microstructural constituents. The fatigue crack path is found to be predominantly intra-granular except for the ones containing > 70% bainite in which it is predominantly inter-granular.

Keywords: bainite, dual phase steel, fatigue crack growth rate, long crack fatigue threshold, short crack fatigue threshold

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Authors: Yen-Fen Shen, Meng-Fan Li

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The study aims to investigate the effect of full-body vertical rhythmic training on fatigue, physical activity, and quality of life among middle-aged and elderly hemodialysis patients. The study adopted a quasi-experimental research method and recruited 43 long-term hemodialysis patients from a medical center in northern Taiwan, with 23 and 20 participants in the experimental and control groups, respectively. The experimental group received full-body vertical rhythmic training as an intervention, while the control group received standard hemodialysis care without any intervention. Both groups completed the measurements by using "Fatigue Scale", "Physical Activity Scale" and "Chinese version of the Kidney Disease Quality of Life Questionnaire" before and after the study. The experimental group underwent a 10-minute full-body vertical rhythmic training three times per week, which lasted for eight weeks before receiving regular hemodialysis treatment. The data were analyzed by SPSS 25 software, including descriptive statistics such as frequency distribution, percentages, means, and standard deviations, as well as inferential statistics, including chi-square, independent samples t-test, and paired samples t-test. The study results are summarized as follows: 1. There were no significant differences in demographic variables, fatigue, physical activity, and quality of life between the experimental and control groups in the pre-test. 2. After the intervention of the “full-body vertical rhythmic training,” the experimental group showed significantly better results in the category of "feeling tired and fatigued in the lower back", "physical functioning role limitation", "bodily pain", "social functioning", "mental health", and "impact of kidney disease on life quality." 3. The paired samples t-test results revealed that the control group experienced significant differences between the pre-test and post-test in the categories of feeling tired and fatigued in the lower back, bodily pain, social functioning mental health, and impact of kidney disease on life quality, with scores indicating a decline in life quality. Conversely, the experimental group only showed a significant worsening in bodily pain" and the impact of kidney disease on life quality, with lower change values compared to the control group. Additionally, there was an improvement in the condition of "feeling tired and fatigued in the lower back" for the experimental group. Conclusion: The intervention of the “full-body vertical rhythmic training” had a certain positive effect on the quality of life of the experimental group. While it may not entirely enhance patients' quality of life, it can mitigate the negative impact of kidney disease on certain aspects of the body. The study provides clinical practice, nursing education, and research recommendations based on the results and discusses the limitations of the research.

Keywords: hemodialysis, full-body vertical rhythmic training, fatigue, physical activity, quality of life

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Authors: Peninah Agaba, Monica Magadi, Bev Orton

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Uganda is one of the countries with high maternal mortality (336/100,000) where adolescents account for 24 percent of the total maternal deaths. Research shows that use of maternal health services may prevent some of these deaths and good provider attitudes attract adolescents to use the services. However, poor health provider’s attitudes discourage adolescents from seeking the services during the maternity period. This study explores the experiences of unmarried female adolescents at the health facilities during the maternity period. The study population is unmarried adolescent girls aged 10-19 years who were pregnant or had given birth within three years before the interview. This is a special interest group that requires attention throughout this period. Most of the pregnancies among unmarried adolescents are unwanted; as a result, many of them have been abused and neglected by parents and close family members including partners who deny fatherhood of the pregnancy/child. These adolescents hope to find comfort from health providers like being listened to during counseling, not abused and judged; unfortunately this is not the case always. The research was approved by the University of Hull, School of Education and Social Sciences ethics review committee, Mildmay Uganda Research Ethics Committee and Uganda National Council of Science and Technology. The study was carried out in Bushenyi and Kibale districts in Western Uganda. Fourteen in-depth interviews and seven focus group discussions were completed in the local languages and later transcribed to English language. Thematic analysis to identify the themes was done. Adolescents were aged 16-19 years, two had become pregnant before 15 years. Most had not completed secondary education; none had tertiary education and three of the 14 IDI adolescent participants wanted to get pregnant. Analysis shows varied experiences; most adolescents were abused verbally and physically by the health providers due to their young age of pregnancy, lack of essential items during this period (maternity dresses, children clothes, delivery kit) and fear of labour pains. Another cause for abuse was these adolescents coming for antenatal care with no partners yet the implementation of a policy on increasing male involvement in reproductive health in Uganda requires them to attend antenatal care with their partners and most of these unmarried adolescents have no partners to accompany them. Despite the above challenges, the study also identified the care some of these unmarried adolescents received during the maternity visits for example they were not abused, were provided with appropriate information and supported with child care. The study identified abuse and support the unmarried adolescents received during the maternity period. Efforts to provide adolescents with adequate information including what to expect during labour by providers and provision of basic needs are essential. Health providers should have trainings on client care especially how to embrace unmarried adolescents when they come to access maternity services. More so, the policy on improving male involvement in RH issues need to be considerate of unmarried adolescents who in most cases do not have the partners to go with to access maternity care.

Keywords: abuse, maternity care, Uganda, unmarried, adolescents

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Authors: Sadia Munir, Diana White, Aya Albahri, Pratiwi Hastania, Eltahir Mohamed, Mahmood Khan, Fathima Mohamed, Ayat Kadhi, Haila Saleem

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Preeclampsia is a major complication of pregnancy. Prediction and management of preeclampsia is a challenge for obstetricians. To our knowledge, no major progress has been achieved in the prevention and early detection of preeclampsia. There is very little known about the clear treatment path of this disorder. Preeclampsia puts both mother and baby at risk of several short term- and long term-health problems later in life. There is huge health service cost burden in the health care system associated with preeclampsia and its complications. Preeclampsia is divided into two different types. Early onset preeclampsia develops before 34 weeks of gestation, and late onset develops at or after 34 weeks of gestation. Different genetic and environmental factors, prognosis, heritability, biochemical and clinical features are associated with early and late onset preeclampsia. Prevalence of preeclampsia greatly varies all over the world and is dependent on ethnicity of the population and geographic region. To authors best knowledge, no published data on preeclampsia exist in Qatar. In this study, we are reporting the incidence of preeclampsia in Qatar. The purpose of this study is to compare the incidence and risk factors of both early onset and late onset preeclampsia in Qatar. This retrospective longitudinal cohort study was conducted using data from the hospital record of Women’s Hospital, Hamad Medical Corporation (HMC), from May 2014-May 2016. Data collection tool, which was approved by HMC, was a researcher made extraction sheet that included information such as blood pressure during admission, socio demographic characteristics, delivery mode, and new born details. A total of 1929 patients’ files were identified by the hospital information management when they apply codes of preeclampsia. Out of 1929 files, 878 had significant gestational hypertension without proteinuria, 365 had preeclampsia, 364 had severe preeclampsia, and 188 had preexisting hypertension with superimposed proteinuria. In this study, 78% of the data was obtained by hospital electronic system (Cerner) and the remaining 22% was from patient’s paper records. We have gone through detail data extraction from 560 files. Initial data analysis has revealed that 15.02% of pregnancies were complicated with preeclampsia from May 2014-May 2016. We have analyzed difference in the two different disease entities in the ethnicity, maternal age, severity of hypertension, mode of delivery and infant birth weight. We have identified promising differences in the risk factors of early onset and late onset preeclampsia. The data from clinical findings of preeclampsia will contribute to increased knowledge about two different disease entities, their etiology, and similarities/differences. The findings of this study can also be used in predicting health challenges, improving health care system, setting up guidelines, and providing the best care for women suffering from preeclampsia.

Keywords: preeclampsia, incidence, risk factors, maternal

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Authors: Ayse Gul Bilen

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Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants that are used clinically for the treatment of anxiety disorders, obsessive-compulsive disorder (OCD), panic disorders and eating disorders. The first SSRI, fluoxetine (sold under the brand names Prozac and Sarafem among others), had an adverse effect profile better than any other available antidepressant when it was introduced because of its selectivity for serotonin receptors. They have been considered almost free of side effects and have become widely prescribed, however questions about the safety and tolerability of SSRIs have emerged with their continued use. Most SSRI side effects are dose-related and can be attributed to serotonergic effects such as nausea. Continuous use might trigger adverse effects such as hyponatremia, tremor, nausea, weight gain, sleep disturbance and sexual dysfunction. Moderate toxicity can be safely observed in the hospital for 24 hours, and mild cases can be safely discharged (if asymptomatic) from the emergency department once cleared by Psychiatry in cases of intentional overdose and after 6 to 8 hours of observation. Although fluoxetine is relatively safe in terms of overdose, it might still be cardiotoxic and inhibit platelet secretion, aggregation, and plug formation. There have been reported clinical cases of seizures, cardiac conduction abnormalities, and even fatalities associated with fluoxetine ingestions. While the medical literature strongly suggests that most fluoxetine overdoses are benign, emergency physicians need to remain cognizant that intentional, high-dose fluoxetine ingestions may induce seizures and can even be fatal due to cardiac arrhythmia. Our case is a 35-year old female patient who was sent to ER with symptoms of confusion, amnesia and loss of orientation for time and location after being found wandering in the streets unconsciously by police forces that informed 112. Upon laboratory examination, no pathological symptom was found except sinus tachycardia in the EKG and high levels of aspartate transaminase (AST) and alanine transaminase (ALT). Diffusion MRI and computed tomography (CT) of the brain all looked normal. Upon physical and sexual examination, no signs of abuse or trauma were found. Test results for narcotics, stimulants and alcohol were negative as well. There was a presence of dysrhythmia which required admission to the intensive care unit (ICU). The patient gained back her conscience after 24 hours. It was discovered from her story afterward that she had been using fluoxetine due to post-traumatic stress disorder (PTSD) for 6 months and that she had attempted suicide after taking 3 boxes of fluoxetine due to the loss of a parent. She was then transferred to the psychiatric clinic. Our study aims to highlight the need to consider toxicologic drug use, in particular, the abuse of selective serotonin reuptake inhibitors (SSRIs), which have been widely prescribed due to presumed safety and tolerability, for diagnosis of patients applying to the emergency room (ER).

Keywords: abuse, amnesia, fluoxetine, intoxication, SSRI

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Authors: Yuvraj Singh Dangi, Brajesh Kumar Tiwari, Ashok Kumar Jain, Kamta Prasad Namdeo

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The potential use of liposomes as drug carriers by i.v. injection is limited by their low stability in blood stream. Firstly, phospholipid exchange and transfer to lipoproteins, mainly HDL destabilizes and disintegrates liposomes with subsequent loss of content. To avoid the pain associated with injection and to obtain better patient compliance studies concerning various dosage forms, have been developed. Conventional liposomes (unilamellar and multilamellar) have certain drawbacks like low entrapment efficiency, stability and release of drug after single breach in external membrane, have led to the new type of liposomal systems. The challenge has been successfully met in the form of Double Liposomes (DL). DL is a recently developed type of liposome, consisting of smaller liposomes enveloped in lipid bilayers. The outer lipid layer of DL can protect inner liposomes against various enzymes, therefore DL was thought to be more effective than ordinary liposomes. This concept was also supported by in vitro release characteristics i.e. DL formation inhibited the release of drugs encapsulated in inner liposomes. DL consists of several small liposomes encapsulated in large liposomes, i.e., multivesicular vesicles (MVV), therefore, DL should be discriminated from ordinary classification of multilamellar vesicles (MLV), large unilamellar vesicles (LUV), small unilamellar vesicles (SUV). However, for these liposomes, the volume of inner phase is small and loading volume of water-soluble drugs is low. In the present study, the potential of phosphatidylethanolamine (PE) lipid anchored double liposomes (DL) to incorporate two drugs in a single system is exploited as a tool to augment the H. pylori eradication rate. Preparation of DL involves two steps, first formation of primary (inner) liposomes by thin film hydration method containing one drug, then addition of suspension of inner liposomes on thin film of lipid containing the other drug. The success of formation of DL was characterized by optical and transmission electron microscopy. Quantitation of DL-bacterial interaction was evaluated in terms of percent growth inhibition (%GI) on reference strain of H. pylori ATCC 26695. To confirm specific binding efficacy of DL to H. pylori PE surface receptor we performed an agglutination assay. Agglutination in DL treated H. pylori suspension suggested selectivity of DL towards the PE surface receptor of H. pylori. Monotherapy is generally not recommended for treatment of a H. pylori infection due to the danger of development of resistance and unacceptably low eradication rates. Therefore, combination therapy with amoxicillin trihydrate (AMOX) as anti-H. pylori agent and ranitidine bismuth citrate (RBC) as antisecretory agent were selected for the study with an expectation that this dual-drug delivery approach will exert acceptable anti-H. pylori activity.

Keywords: Helicobacter pylorI, amoxicillin trihydrate, Ranitidine Bismuth citrate, phosphatidylethanolamine, multi vesicular systems

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Authors: Tristan R. Fraser, Christopher D. Steadman, Christopher J. Boos

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Myopericarditis is an inflammation syndrome characterised by clinical diagnostic criteria for pericarditis, such as chest pain, combined with evidence of myocardial involvement, such as elevation of biomarkers of myocardial damage, e.g., troponins. It can rarely be a complication of therapeutics used for dysregulated immune-mediated diseases such as inflammatory bowel disease (IBD), for example, mesalazine. The infrequency of mesalazine-induced myopericarditis adds to the challenge in its recognition. Rapid diagnosis and the early introduction of treatment are crucial. This case report follows a 24-year-old professional footballer with a past medical history of ulcerative colitis, recently started on mesalazine for disease control. Three weeks after mesalazine was initiated, he was admitted with fever, shortness of breath, and chest pain worse whilst supine and on deep inspiration, as well as elevated venous blood cardiac troponin T level (cTnT, 288ng/L; normal: <13ng/L). Myocarditis was confirmed on initial inpatient cardiac MRI, revealing the presence of florid myocarditis with preserved left ventricular systolic function and an ejection fraction of 67%. This was a longitudinal case study following the progress of a single individual with myopericarditis over four acute hospital admissions over nine weeks, with admissions ranging from two to five days. Parameters examined included clinical signs and symptoms, serum troponin, transthoracic echocardiogram, and cardiac MRI. Serial measurements of cardiac function, including cardiac MRI and transthoracic echocardiogram, showed progressive deterioration of cardiac function whilst mesalazine was continued. Prior to cessation of mesalazine, transthoracic echocardiography revealed a small global pericardial effusion of < 1cm and worsening left ventricular systolic function with an ejection fraction of 45%. After recognition of mesalazine as a potential cause and consequent cessation of the drug, symptoms resolved, with cardiac MRI performed as an outpatient showing resolution of myocardial oedema. The patient plans to make a return to competitive sport. Patients suffering from myopericarditis are advised to refrain from competitive sport for at least six months in order to reduce the risk of cardiac remodelling and sudden cardiac death. Additional considerations must be taken in individuals for whom competitive sport is an essential component of their livelihood, such as professional athletes. Myopericarditis is an uncommon, however potentially serious medical condition with a wide variety of aetiologies, including viral, autoimmune, and drug-related causes. Management is mainly supportive and relies on prompt recognition and removal of the aetiological process. Mesalazine-induced myopericarditis is a rare condition; as such increasing awareness of mesalazine as a precipitant of myopericarditis is vital for optimising the management of these patients.

Keywords: myopericarditis, mesalazine, inflammatory bowel disease, professional athlete

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Authors: Sakinah Idris, Gabrine Jagersma, Bjorn Jaime Van Pelt, Kirstin Greaves-Lord

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Background: The PEERS (Program for the Education and Enrichment of Relational Skills) intervention can be considered a well-established, evidence-based intervention in the USA. However, testing the efficacy of cultural adaptations of PEERS is still ongoing. More and more, the involvement of all stakeholders in the development and evaluation of interventions is acknowledged as crucial for the longer term implementation of interventions across settings. Therefore, in the current project, teens with ASD (Autism Spectrum Disorder), their neurotypical peers, parents, teachers, as well as clinicians were involved in the development and evaluation of the Dutch version of PEERS. Objectives: The current presentation covers (1) the formative phase and (2) the preliminary adaptation test phase of the cultural adaptation of evidence-based interventions. In the formative phase, we aim to describe the process of adaptation of the PEERS program to the Dutch culture and care system. In the preliminary adaptation phase, we will present results from the preliminary adaptation test among 32 adolescents with ASD. Methods: In phase 1, a group discussion on common vocabulary was conducted among 70 teenagers (and their teachers) from special and regular education aged 12-18 years old. This inventory concerned 14 key constructs from PEERS, e.g., areas of interests, locations for making friends, common peer groups and crowds inside and outside of school, activities with friends, commonly used ways for electronic communication, ways for handling disagreements, and common teasing comebacks. Also, 15 clinicians were involved in the translation and cultural adaptation process. The translation and cultural adaptation process were guided by the research team, and who included input and feedback from all stakeholders through an iterative feedback incorporation procedure. In phase 2, The parent-reported Social Responsiveness Scale (SRS), the Test of Adolescent Social Skills Knowledge (TASSK), and the Quality of Socialization Questionnaire (QSQ) were assessed pre- and post-intervention to evaluate potential treatment outcome. Results: The most striking cultural adaptation - reflecting the standpoints of all stakeholders - concerned the strategies for handling rumors and gossip, which were suggested to be taught using a similar approach as the teasing comebacks, more in line with ‘down-to-earth’ Dutch standards. The preliminary testing of this adapted version indicated that the adolescents with ASD significantly improved their social knowledge (TASSK; t₃₁ = -10.9, p < .01), social experience (QSQ-Parent; t₃₁ = -4.2, p < .01 and QSQ-Adolescent; t₃₂ = -3.8, p < .01), and in parent-reported social responsiveness (SRS; t₃₃ = 3.9, p < .01). In addition, subjective evaluations of teens with ASD, their parents and clinicians were positive. Conclusions: In order to further scrutinize the effectiveness of the Dutch version of the PEERS intervention, we recommended performing a larger scale randomized control trial (RCT) design, for which we provide several methodological considerations.

Keywords: cultural adaptation, PEERS, preliminary testing, translation

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Authors: Fangfang Wang, Tianjing Wang, Leyi Fu, Feng Yun, Ningning Xie, Jue Zhou, Fan Qu

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Background: Ferroptosis, a recently discovered form of programmed cell death characterized by iron-dependent lipid peroxidation, may be linked to polycystic ovary syndrome (PCOS). Diseases marked by iron overload have been correlated with ferroptosis. Coincidently, investigations have revealed anomalies in iron metabolism among women with PCOS; however, there were inconsistencies in the evidence. Objective and Rationale: This review aimed to comprehensively explore the potential relationship between ferroptosis and PCOS by investigating the differences in iron metabolism among women with PCOS in comparison to a control group. Additionally, a narrative synthesis was provided on the past research status regarding the association between PCOS and ferroptosis. Methods: A systematic search of the literature was performed using PubMed, Embase, Web of Science from inception up to December 2022. Search terms relating to assisted PCOS, ferroptosis, and iron metabolism were used. PRISMA guidance was followed. RevMan 5.4 was utilized for conducting the meta-analysis, wherein the investigated outcomes included iron status (ferritin, iron, transferrin saturation) and a systemic iron-regulatory hormone (hepcidin). A narrative synthesis was performed to explore the correlation between PCOS and ferroptosis. Results: In the meta-analysis comprising a total of 16 studies, significant differences in serum ferritin levels between the PCOS group and the control group were observed (15 studies, standardized mean difference (SMD): 0.41, 95% CI: 0.22 to 0.59, P<0.01). This indicates elevated serum ferritin levels in PCOS patients compared to women without PCOS. The transferrin saturation in PCOS patients was significantly higher than that in the control group (3 studies, mean difference (MD): 4.39, 95% CI: 1.67 to 7.11, P<0.01). Regarding serum iron (6 studies, SMD: 0.05, 95% CI: -0.24 to 0.33, P=0.75) and serum hepcidin (4 studies, SMD: -0.44, 95% CI: -1.41 to 0.52, P=0.37), no statistically significant differences were observed between the PCOS group and the control group. Other studies have found that ferroptosis is involved in the occurrence and development of PCOS, offering valuable insights for guiding potential treatment measures and prognosis evaluation of PCOS. In addition, ferroptosis is involved in the miscarriage of PCOS-like rats; thus, controlling ferroptosis might improve pregnancy outcomes in PCOS. Conclusions: The observation of a significant elevation in serum ferritin and transferrin saturation levels in women with PCOS may suggest an underlying disturbance in iron metabolism, potentially inducing the activation of ferroptosis. Further research is imperative to elucidate the underlying pathophysiology, providing insights for potential preventive measures and therapeutic strategies. Limitation: There are some limitations as follows: First, due to limited extractable information, we excluded purely abstract publications and non-English publications. Second, the majority of original articles were case-control studies, making it difficult to determine the causal relationship between iron metabolism abnormalities and the onset of PCOS. Third, there is substantial heterogeneity in the definition of PCOS.

Keywords: polycystic ovary syndrome, ferroptosis, iron metabolism, systematic review and meta-analysis

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Authors: Joao Almeida, Ana Azevedo, Myriam Kanoun-Boule, Maria Ines Santos, Antonio Tadeu

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The effects of the increasing expansion of cities and climate changes have encouraged European countries and regions to adopt nature-based solutions with ability to mitigate environmental issues and improve life in cities. Among these strategies, green roofs and urban gardens have been considered ingenious solutions, since they have the desirable potential to improve air quality, prevent floods, reduce the heat island effect and restore biodiversity in cities. However, an additional consumption of fresh water and mineral nutrients is necessary to sustain larger green urban areas. This communication discusses the main technical features of a new system to manage urine recovery at the building level and its application in green roofs. The depletion of critical nutrients like phosphorus constitutes an emergency. In turn, their elimination through urine is one of the principal causes for their loss. Thus, urine recovery in buildings may offer numerous advantages, constituting a valuable fertilizer abundantly available in cities and reducing the load on wastewater treatment plants. Although several urine-diverting toilets have been developed for this purpose and some experiments using urine directly in agriculture have already been carried out in Europe, several challenges have emerged with this practice concerning collection, sanitization, storage and application of urine in buildings. To our best knowledge, current buildings are not designed to receive these systems and integrated solutions with ability to self-manage the whole process of urine recovery, including separation, maturation and storage phases, are not known. Additionally, if from a hygiene point of view human urine may be considered a relatively safe fertilizer, the risk of disease transmission needs to be carefully analysed. A reduction in microorganisms can be achieved by storing the urine in closed tanks. However, several factors may affect this process, which may result in a higher survival rate for some pathogens. In this work, urine effluent was collected under real conditions, stored in closed containers and kept in climatic chambers under variable conditions simulating cold, temperate and tropical climates. These samples were subjected to a first physicochemical and microbiological control, which was repeated over time. The results obtained so far suggest that maturation conditions were reached for all the three temperatures and that a storage period of less than three months is required to achieve a strong depletion of microorganisms. The authors are grateful for the Project WashOne (POCI-01-0247-FEDER-017461) funded by the Operational Program for Competitiveness and Internationalization (POCI) of Portugal 2020, with the support of the European Regional Development Fund (FEDER).

Keywords: sustainable green roofs and urban gardens, urban nutrient cycle, urine-based fertilizers, urine recovery in buildings

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Authors: Zikun Li, Regine Talleyrand

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Negative body image is one of the most common causes of eating disorders, and it is not only happening to women. Regardless of the increasing attention that researchers and practitioners have been paying to the male population and their body image concerns, men of color have yet to be fully represented or studied. Given the consensus that the sociocultural experiences of people of color may play a significant role in their health and well-being, this study focused on assessing the mechanism through which sociocultural factors may influence men of color’s perceptions of body image. In particular, this study focused on untangling how interpersonal and media pressure, as well as ethnic-racial identities and perceptions, would impact body dissatisfaction in terms of muscularity, body fat, and height in men of color and how this mechanism is moderated across different ethnic-racial groups. The structural equation modeling approach was therefore applied to achieve the research goal. With the sample size of 181 self-identified Black, Indigenous, and People of Color male participants aged 20-50 (M=33.33, SD=6.9) through surveying on Amazon’s MTurk platform, the proposed model achieved a modestly acceptable model fit with the pooled sample, X2(836) = 1412.184, CFI = 0.900, RMSEA = 0.062 [0.056, 0.067]. And SRMR = 0.088, And it explained 89.5% of the variance in body dissatisfaction. The results showed that of all the direct effects on body dissatisfaction, interpersonal appearance pressure exhibited the strongest effect (β = 0.410***), followed by media appearance pressure (β = 0.272**) and self-hatred feeling (β = 0.245**). The ethnic-racial related factors (i.e., stereotype endorsement, ethnic-racial salience, and nationalistic assimilation) statistically influenced body dissatisfaction through the mediators of media appearance pressure and/or self-hatred feeling. Furthermore, the moderation analysis between Black/African American men and non-Black/African American men revealed the substantial differences in how ethnic/racial identity impacts one’s perception of body image, and the Black/African American men were found to be influenced by sociocultural factors at a higher level, compared with their counterparts. The impacts of demographic characteristics (i.e., SES, weight, height) on body dissatisfaction were also examined. Instead of considering interpersonal appearance pressure and media pressure as two subscales under one construct, this study considered them as two separate and distinct sociocultural factors. The good model fit to the data indicates this rationality and encourages scholars to reconsider the impacts of two sources of social pressures on body dissatisfaction. In addition, this study also provided empirical evidence of the moderation effect existing within the population of men of color, which reveals the heterogeneity existing across different ethnic-racial groups and implies the necessity to study individual ethnic-racial groups so as to better understand the mechanism of sociocultural influences on men of color’s body dissatisfaction. These findings strengthened the current understanding of the body image concerns exciting among men of color and meanwhile provided empirical evidence for practitioners to provide tailored health prevention and treatment options for this growing population in the United States.

Keywords: men of color, body image concerns, sociocultural factors, structural equation modeling

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Authors: Anthony S. Machi, Joseph Minardi

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We present a case report of left atrial myxoma diagnosed by bedside transesophageal (TEE) ultrasound. Left atrial myxoma is the most common benign cardiac tumor and can obstruct blood flow and cause valvular insufficiency. Common symptoms consist of dyspnea, pulmonary edema and other features of left heart failure in addition to thrombus release in the form of tumor fragments. The availability of bedside ultrasound equipment is essential for the quick diagnosis and treatment of various emergency conditions including cardiac neoplasms. A 48-year-old Caucasian female with a four-year history of an untreated renal mass and anemia presented to the ED with two months of sharp, intermittent, bilateral flank pain radiating into the abdomen. She also reported intermittent vomiting and constipation along with generalized body aches, night sweats, and 100-pound weight loss over last year. She had a CT in 2013 showing a 3 cm left renal mass and a second CT in April 2016 showing a 3.8 cm left renal mass along with a past medical history of diverticulosis, chronic bronchitis, dyspnea on exertion, uncontrolled hypertension, and hyperlipidemia. Her maternal family history is positive for breast cancer, hypertension, and Type II Diabetes. Her paternal family history is positive for stroke. She was a current everyday smoker with an 11 pack/year history. Alcohol and drug use were denied. Physical exam was notable for a Grade II/IV systolic murmur at the right upper sternal border, dyspnea on exertion without angina, and a tender left lower quadrant. Her vitals and labs were notable for a blood pressure of 144/96, heart rate of 96 beats per minute, pulse oximetry of 96%, hemoglobin of 7.6 g/dL, hypokalemia, hypochloremia, and multiple other abnormalities. Physicians ordered a CT to evaluate her flank pain which revealed a 7.2 x 8.9 x 10.5 cm mixed cystic/solid mass in the lower pole of the left kidney and a filling defect in the left atrium. Bedside TEE was ordered to follow up on the filling defect. TEE reported an ejection fraction of 60-65% and visualized a mobile 6 x 3 cm mass in the left atrium attached to the interatrial septum extending into the mitral valve. Cardiothoracic Surgery and Urology were consulted and confirmed a diagnosis of left atrial myxoma and clear cell renal cell carcinoma. The patient returned a week later due to worsening nausea and vomiting and underwent emergent nephrectomy, lymph node dissection, and colostomy due to a necrotic colon. Her condition declined over the next four months due to lung and brain metastases, infections, and other complications until she passed away.

Keywords: bedside ultrasound, echocardiography, emergency medicine, left atrial myxoma

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Authors: Melanie Francois, Gilles Caboche, Frederic Demoisson, Francois Maeght, Maria Paola Carpanese, Lionel Combemale, Pascal Briois

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Finding new clean, and efficient way for energy production is one of the actual global challenges. Advances in fuel cell technology have shown that, for few years, Protonic Ceramic Fuel Cell (PCFC) has attracted much attention in the field of new hydrogen energy thanks to their lower working temperature, possible higher efficiency, and better durability than classical SOFC. On the contrary of SOFC, where O²⁻ oxygen ion is the charge carrier, PCFC works with H⁺ proton as a charge carrier. Consequently, the lower activation energy of proton diffusion compared to the one of oxygen ion explains those benefits and allows PCFC to work in the 400-600°C temperature range. Doped-BaCeO₃ is currently the most chosen material for this application because of its high protonic conductivity; for example, BaCe₀.₉Y₀.₁O₃ δ exhibits a total conductivity of 1.5×10⁻² S.cm⁻¹ at 600°C in wet H₂. However, BaCeO₃ based perovskite has low stability in H₂O and/or CO₂ containing atmosphere, which limits their practical application. On the contrary, BaZrO₃ based perovskite exhibits good chemical stability but lower total conductivity than BaCeO₃ due to its larger grain boundary resistance. By substituting zirconium with 20% of yttrium, it is possible to achieve a total conductivity of 2.5×10⁻² S.cm⁻¹ at 600°C in wet H₂. However, the high refractory property of BaZr₀.₈Y₀.₂O₃-δ (noted BZY20) causes problems to obtain a dense membrane with large grains. Thereby, using a synthesis process that gives fine particles could allow better sinterability and thus decrease the number of grain boundaries leading to a higher total conductivity. In this work, BaZr₀.₈Y₀.₂O₃-δ have been synthesized by classical batch hydrothermal device and by a continuous hydrothermal device developed at ICB laboratory. The two variants of this process are able to work in supercritical conditions, leading to the formation of nanoparticles, which could be sintered at a lower temperature. The as-synthesized powder exhibits the right composition for the perovskite phase, impurities such as BaCO₃ and YO-OH were detected at very low concentration. Microstructural investigation and densification rate measurement showed that the addition of 1 wt% of ZnO as sintering aid and a sintering at 1550°C for 5 hours give high densified electrolyte material. Furthermore, it is necessary to heat the synthesized powder prior to the sintering to prevent the formation of secondary phases. It is assumed that this thermal treatment homogenizes the crystal structure of the powder and reduces the number of defects into the bulk grains. Electrochemical impedance spectroscopy investigations in various atmospheres and a large range of temperature (200-700°C) were then performed on sintered samples, and the protonic conductivity of BZY20 has been highlighted. Further experiments on half-cell, NiO-BZY20 as anode and BZY20 as electrolyte, are in progress.

Keywords: hydrothermal synthesis, impedance measurement, Y-doped BaZrO₃, proton conductor

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Authors: Naiara Ozamiz Etcebarria, Sonia Ruiz De Azua Garcia, Agurtzane Ortiz Jauregi, Virginia Guillen Cañas

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Introduction: The most relevant competencies of a health professional are an adequate communication capacity, which will influence the satisfaction of professionals and patients, therapeutic compliance, conflict prevention, clinical outcomes´ improvement and efficiency of health services. The ability of Active listening , empathy, assertiveness and social skills, are important abilities to develop in all professions in which there is a relationship with other people. In the field of health, it is even more important to have adequate qualities so that the treatment with the patient will be adequate and satisfactory. We conducted a research with students of third year in the Degree of Medicine with the objectives: - to know how the active listening, empathy, assertiveness and social skills of students are. - to know if there are differences according to different demographic variables, such as sex, language, age, number of siblings and interest in the subject. Material and Methods: The students of the Third year in the Degree of Medicine (N = 212) participated voluntarily. Sociodemographic data were collected. Descriptive and comparative analysis of the averages of the students with respect to active listening, empathy, assertiveness and social skills were performed. Once the questionnaires were collected, they were entered into the SPSS 21 database. Four communicational aspects were evaluated: The active listening questionnaire, the TECA empathy questionnaire, the ACDA questionnaire and the EHS questionnaire Social Skills Scale. The active listening questionnaire assesses these factors: Listening without interruption and less contradiction, Listening with 100% attention, Listening beyond words, Listening encouraging the other to go deeper. The TECA questionnaire of cognitive and affective empathy evaluates: Adoption of perspectives, Emotional Comprehension, Emphasizing stress, Empathic joy. The EHS questionnaire Social Skills Scale: Self-expression in social situations, Defending one's own rights as a consumer, Expressing anger or dissatisfaction, Refusing to do and cutting interactions off, Making requests, Initiating positive interactions with the other sex. The ACDA questionnaire Assertiveness Assessment Scale evaluates self-assertiveness and heteroaservitivity. Applicability: To train these skills is so important for clinical practice of medical students and these capabilities that can be measured in a longitudinal way time. Ethical-legal aspects: The data were anonymous. The study was approved by the Ethics Committee. Results: The students of the Third year in the Degree of Medicine (34.4% Basque speakers and 65.6% Spanish speakers) with average age 20.93, (27.8% men and 72.2% women). There are no differences in social skills between men and women. The Basque speaker students of are more heteroactive (ACDA) than Spanish students. Active listening has a high correlation with social skills, especially with self-expression in social situations. Listening without interruption has a high correlation with self-expression in social situations and initiating positive interactions with the opposite sex. Adoption of perspectives presents a high correlation with auto- assertiveness. Emotional understanding presents a high correlation with positive interactions with the opposite sex. Empathic joy correlates with self-assertiveness, self-expression in social situations, and initiating positive interactions with the opposite sex.

Keywords: active listening, assertiveness, communicational skills, empathy, students of medicine

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Authors: Sameerah A. Al-Hariri Al-Zahrani

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The current study aims at getting acquainted with the impact of the use of some multiple intelligence-based teaching strategies on developing moral intelligence and inferential jurisprudential thinking among secondary school female students. The study has endeavored to answer the following questions: What is the impact of the use of some multiple intelligence-based teaching strategies on developing inferential jurisprudential thinking and moral intelligence among first-year secondary school female students? In the frame of this main research question, the study seeks to answer the following sub-questions: (i) What are the inferential jurisprudential thinking skills among first-year secondary school female students? (ii) What are the components of moral intelligence among first year secondary school female students? (iii) What is the impact of the use of some multiple intelligence‐based teaching strategies (such as the strategies of analyzing values, modeling, Socratic discussion, collaborative learning, peer collaboration, collective stories, building emotional moments, role play, one-minute observation) on moral intelligence among first-year secondary school female students? (iv) What is the impact of the use of some multiple intelligence‐based teaching strategies (such as the strategies of analyzing values, modeling, Socratic discussion, collaborative learning, peer collaboration, collective stories, building emotional moments, role play, one-minute observation) on developing the capacity for inferential jurisprudential thinking of juristic rules among first-year secondary school female students? The study has used the descriptive-analytical methodology in surveying, analyzing, and reviewing the literature on previous studies in order to benefit from them in building the tools of the study and the materials of experimental treatment. The study has also used the experimental method to study the impact of the independent variable (multiple intelligence strategies) on the two dependent variables (moral intelligence and inferential jurisprudential thinking) in first-year secondary school female students’ learning. The sample of the study is made up of 70 female students that have been divided into two groups: an experimental group consisting of 35 students who have been taught through multiple intelligence strategies, and a control group consisting of the other 35 students who have been taught normally. The two tools of the study (inferential jurisprudential thinking test and moral intelligence scale) have been implemented on the two groups as a pre-test. The female researcher taught the experimental group and implemented the two tools of the study. After the experiment, which lasted eight weeks, was over, the study showed the following results: (i) The existence of significant statistical differences (0.05) between the mean average of the control group and that of the experimental group in the inferential jurisprudential thinking test (recognition of the evidence of jurisprudential rule, recognition of the motive for the jurisprudential rule, jurisprudential inferencing, analogical jurisprudence) in favor of the experimental group. (ii) The existence of significant statistical differences (0.05) between the mean average of the control group and that of the experimental group in the components of the moral intelligence scale (sympathy, conscience, moral wisdom, tolerance, justice, respect) in favor of the experimental group. The study has, thus, demonstrated the impact of the use of some multiple intelligence-based teaching strategies on developing moral intelligence and inferential jurisprudential thinking.

Keywords: moral intelligence, teaching, inferential jurisprudential thinking, secondary school

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Authors: Chandan Kundu, Sankar Bhattacharya

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A significant disadvantage of fossil fuel energy production is the considerable amount of carbon dioxide (CO₂) released, which is one of the contributors to climate change. Apart from environmental concerns, changing fossil fuel prices have pushed society gradually towards renewable energy sources in recent years. Biomass is a plentiful and renewable resource and a source of carbon. Recent years have seen increased research interest in generating fuels and chemicals from biomass. Unlike fossil-based resources, biomass is composed of lignocellulosic material, which does not contribute to the increase in atmospheric CO₂ over a longer term. These considerations contribute to the current move of the chemical industry from non-renewable feedstock to renewable biomass. This presentation focuses on generating bio-oil and two major platform chemicals that can potentially improve the environment. Thermochemical processes such as pyrolysis are considered viable methods for producing bio-oil and biomass-based platform chemicals. Fluidized bed reactors, on the other hand, are known to boost bio-oil yields during pyrolysis due to their superior mixing and heat transfer features, as well as their scalability. This review and the associated experimental work are focused on the thermochemical conversion of biomass to bio-oil and two high-value platform chemicals, Levoglucosenone (LGO) and 5-Chloromethyl furfural (5-CMF), in a fluidized bed reactor. These two active molecules with distinct features can potentially be useful monomers in the chemical and pharmaceutical industries since they are well adapted to the manufacture of biologically active products. This process took several meticulous steps. To begin, the biomass was delignified using a peracetic acid pretreatment to remove lignin. Because of its complicated structure, biomass must be pretreated to remove the lignin, increasing access to the carbohydrate components and converting them to platform chemicals. The biomass was then characterized by Thermogravimetric analysis, Synchrotron-based THz spectroscopy, and in-situ DRIFTS in the laboratory. Based on the results, a continuous-feeding fluidized bed reactor system was constructed to generate platform chemicals from pretreated biomass using hydrogen chloride acid-gas as a catalyst. The procedure also yields biochar, which has a number of potential applications, including soil remediation, wastewater treatment, electrode production, and energy resource utilization. Consequently, this research also includes a preliminary experimental evaluation of the biochar's prospective applications. The biochar obtained was evaluated for its CO₂ and steam reactivity. The outline of the presentation will comprise the following: Biomass pretreatment for effective delignification Mechanistic study of the thermal and thermochemical conversion of biomass Thermochemical conversion of untreated and pretreated biomass in the presence of an acid catalyst to produce LGO and CMF A thermo-catalytic process for the production of LGO and 5-CMF in a continuously-fed fluidized bed reactor and efficient separation of chemicals Use of biochar generated from the platform chemicals production through gasification

Keywords: biomass, pretreatment, pyrolysis, levoglucosenone

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Authors: Vanessa G. P. Severino, Eliangela Cristina Candida Costa, Nubia Alves Mariano Teixeira Pires Gomides, Lucilia Kato, Afif Felix Monteiro, Maria Anita Lemos Vasconcelos Ambrosio, Carlos Henrique Gomes Martins

Abstract:

One of the biomes present in Brazil is known as Cerrado, which is a vast tropical savanna ecoregion, particularly in the states of Goiás, Mato Grosso do Sul, Mato Grosso, Tocantins and Minas Gerais. Many species of plants are characterized as endemic and they have therapeutic value for a large part of the population, especially to the rural communities. Given that, the southeastern region of the state of Goiás contains about 21 rural communities, which present a form of organization based on the use of natural resources available. One of these rural communities is named of Coqueiros, where the knowledge about the medicinal plants was very important to this research. Thus, this study focuses on the ethnobotanical survey of this community on the use of Kielmeyera coriacea to treat diseases. From the 37 members interviewed, 76% indicated this species for the treatment of intestinal infection, leukemia, anemia, gastritis, gum pain, toothache, cavity, arthritis, arthrosis, healing, vermifuge, rheumatism, antibiotic, skin problems, mycoses and all kinds of infections. The medicinal properties attributed during the interviews were framed in the body system (disease categories), adapted from ICD 10; thus, 20 indications of use were obtained, among five body systems. Therefore, the root of this species was select to chemical and biological (antioxidant and antimicrobial) studies. From the liquid-liquid extraction of ethanolic extract of root (EER), the hexane (FH), ethyl acetate (FAE), and hydro alcoholic (FHA) fractions were obtained. The chemical profile study of these fractions was performed by LC-MS, identifying major compounds such as δ-tocotrienol, prenylated acylphoroglucinol, 2-hydroxy-1-methoxyxanthone and quercitrin. EER, FH, FAE and FHA were submitted to biological tests. FHA presented the best antioxidant action (EC50 201.53 μg mL-1). EER inhibited the bacterial growth of Streptococcus pyogenes and Pseudomonas aeruginosa, microorganisms associated with rheumatism, at Minimum Inhibitory Concentration (MIC) of 6.25 μg mL-1. In addition, the FH-10 subfraction, obtained from FH fractionation, presented MIC of 1.56 μg mL-1 against S. pneumoniae; EER also inhibited the fungus Candida glabrata (MIC 7.81 μg mL- 1). The FAE-4.7.3 fraction, from the fractionation of FAE, presented MIC of 200 μg mL-1 against Lactobacillus casei, which is one of the causes of caries and oral infections. By the correlation of the chemical and biological data, it is possible to note that the FAE-4.7.3 and FH-10 are constituted 4-hydroxy-2,3-methylenedioxy xanthone, 3-hydroxy-1,2-dimethoxy xanthone, lupeol, prenylated acylphoroglucinol and quercitrin, which could be associated with the biological potential found. Therefore, this study provides an important basis for further investigations regarding the compounds present in the active fractions of K. coriacea, which will permit the establishment of a correlation between ethnobotanical survey and bioactivity.

Keywords: biological activity, ethnobotanical survey, Kielmeyera coriacea Mart., LC-MS profile

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Authors: Wang Shuai, Su Rong, K. J.Tseng, V. Viswanathan, S. Ramakrishna

Abstract:

The More-Electric-Aircraft concept in aircraft industry levies an increasing demand on the embedded starter/generators (ESG). The high-speed and high-temperature environment within an engine poses great challenges to the operation of such machines. In view of such challenges, squirrel cage induction machines (SCIM) have shown advantages due to its simple rotor structure, absence of temperature-sensitive components as well as low torque ripples etc. The tight operation constraints arising from typical ESG applications together with the detailed operation principles of SCIMs have been exploited to derive the mathematical interpretation of the ESG-SCIM design process. The resultant non-linear mathematical treatment yielded unique solution to the SCIM design problem for each configuration of pole pair number p, slots/pole/phase q and conductors/slot zq, easily implemented via loop patterns. It was also found that not all configurations led to feasible solutions and corresponding observations have been elaborated. The developed mathematical procedures also proved an effective framework for optimization among electromagnetic, thermal and mechanical aspects by allocating corresponding degree-of-freedom variables. Detailed 3D FEM analysis has been conducted to validate the resultant machine performance against design specifications. To obtain higher power ratings, electrical machines often have to increase the slot areas for accommodating more windings. Since the available space for embedding such machines inside an engine is usually short in length, axial air gap arrangement appears more appealing compared to its radial gap counterpart. The aforementioned approach has been adopted in case studies of designing series of AFIMs and RFIMs respectively with increasing power ratings. Following observations have been obtained. Under the strict rotor diameter limitation AFIM extended axially for the increased slot areas while RFIM expanded radially with the same axial length. Beyond certain power ratings AFIM led to long cylinder geometry while RFIM topology resulted in the desired short disk shape. Besides the different dimension growth patterns, AFIMs and RFIMs also exhibited dissimilar performance degradations regarding power factor, torque ripples as well as rated slip along with increased power ratings. Parametric response curves were plotted to better illustrate the above influences from increased power ratings. The case studies may provide a basic guideline that could assist potential users in making decisions between AFIM and RFIM for relevant applications.

Keywords: axial flux induction machine, electrical starter/generator, finite element analysis, squirrel cage induction machine

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Authors: Richele P. Severino, Maria M. F. Alchaar, Lorena R. F. De Sousa, Patrik S. Vital, Ana G. Silva, Rosy I. M. A. Ribeiro

Abstract:

Recognized as a global biodiversity hotspot, the Cerrado (Brazil) presents an extreme abundance of endemic species and it is considered to be one of the biologically richest tropical savanna regions in the world. Erythroxylum genus is found in Cerrado and chemically is characterized by the presence of tropane alkaloids, among them cocaine, a natural alkaloid produced by Erythroxylum coca Lam., which was used as a local anesthetic in small surgeries. However, cocaine gained notoriety due to its psychoactive activity in the Central Nervous System (CNS), becoming one of the major problems of public health today. Some species of Erythroxylum are referred to in the literature as having pharmacological potential, which provide alkaloids, terpenoids, and flavonoids. E. vacciniifolium Mart., commonly known as 'catuaba', is used as a central nervous system stimulant and has aphrodisiac properties and E. pelleterianum A. St.-Hil. in the treatment of stomach pains. Already E. myrsinites Mart. and E. suberosum A. St.-Hil. are used in the tannery industry. Species of Erythroxylum are also used in folk medicine for various diseases, against diabetes, antiviral, fungicidal, cytotoxicity, among others. The Cerrado is recognized as the richer savannah in the world in biodiversity but little explored from the chemical view. In our on-going study of the chemistry of Erythroxylum genus, we have investigated four specimens collected in central Cerrado of Brazil: E. campestre (EC), E. deciduum (ED), E. suberosum (ES) and E. tortuosum (ET). The cytotoxic activity of extracts was evaluated using HeLa cells, in vitro assays. The chemical investigation was performed preparing the extracts using n-hexane (H), dichloromethane (D), ethyl acetate (E) and methanol (M). The cells were treated with increasing concentrations of extracts (50, 75 and 100 μg/mL) diluted in DMSO (1%) and DMEM (0.5% FBS and 1% P/S). The IC₅₀ values were determined measured spectrophotometrically at 570 nm, after incubation of HeLa cell line for 48 hours using the MTT (SIGMA M5655), and calculated by nonlinear regression analysis using GraphPad Prism software. All the assays were done in triplicate and repeated at least two times. The cytotoxic assays showed some promising results with IC₅₀ values less than 100 μg/mL (ETD = 38.5 μg/mL; ETM = 92.3 μg/mL; ESM = 67.8 μg/mL; ECD = 24.0 μg/mL; ECM = 32.9; EDA = 44.2 μg/mL). The chemical profile study of ethyl acetate (E) and methanolic (M) extracts of E. tortuosum leaves was performed by LC-MS, and the structures of the compounds were determined by analysis of ¹H, HSQC and HMBC spectra, and confirmed by comparison with the literature data. The investigation led to six substances: α-amyrin, β-amyrin, campesterol, stigmastan-3,5-diene, β-sitosterol and 7,4’-di-O-methylquercetin-3-O-β-rutinoside, with flavonoid the major compound of extracts. By alkaline extraction of the methanolic extract, it was possible to identify three alkaloids: tropacocaine, cocaine and 6-methoxy-8-methyl-8-azabicyclo[3.2.1]octan-3-ol. The results obtained are important for the chemical knowledge of the Cerrado biodiversity and brought a contribution to the chemistry of Erythroxylum genus.

Keywords: cytotoxicity, Erythroxylum, chemical profile, secondary metabolites

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Authors: Lilian Nantume Wampande

Abstract:

Group-based strategies in the delivery of HIV care have opened up new avenues not only for meaningful participation for HIV positive people but also platforms for deconstruction and reconstruction of knowledge about living with the virus. Yet the contributions of such strategies among patients who live in high risk areas are still not explored. This case study research assessed the impact of HIV support networks on sexual health outcomes of HIV positive out-of-school adolescents residing in fishing islands of Kalangala in Uganda. The study population was out-of-school adolescents living with HIV and their sexual partners (n=269), members of their households (n=80) and their health service providers (n=15). Data were collected via structured interviews, observations and focus group discussions between August 2016 and March 2017. Data was then analyzed inductively to extract key themes related to the approaches and outcomes of the groups’ activities. The study findings indicate that support groups unite HIV positive adolescents in a bid for social renegotiation to achieve change but individual constraints surpass the groups’ intentions. Some adolescents for example reported increased fear which led to failure to cope, sexual violence, self-harm and denial of status as a result of the high expectations placed on them as members of the support groups. Further investigations around this phenomenon show that HIV networks play a monotonous role as information sources for HIV positive out-of-school adolescents which limit their creativity to seek information elsewhere. Results still indicate that HIV adolescent groups recognize the complexity of long-term treatment and stay in care leading to improved immunity for the majority yet; there is still scattered evidence about how effective they are among adolescents at different phases in the disease trajectory. Nevertheless, the primary focus of developing adolescent self-efficacy and coping skills significantly address a range of disclosure difficulties and supports autonomy. Moreover, the peer techniques utilized in addition to the almost homogeneous group characteristics accelerates positive confidence, hope and belongingness. Adolescent HIV-support groups therefore have the capacity to both improve and/or worsen sexual health outcomes for a young adolescent who is out-of-school. Communication interventions that seek to increase awareness about ‘self’ should therefore be emphasized more than just fostering collective action. Such interventions should be sensitive to context and gender. In addition, facilitative support supervision done by close and trusted health care providers, most preferably Village Health Teams (who are often community elected volunteers) would help to follow-up, mentor, encourage and advise this young adolescent in matters involving sexuality and health outcomes. HIV/AIDS prevention programs have extended their efforts beyond individual focus to those that foster collective action, but programs should rekindle interpersonal level strategies to address the complexity of individual behavior.

Keywords: adolescent, HIV, support groups, Uganda

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Authors: Kamelia Hamza

Abstract:

Background: Proton pump inhibitors (PPIs) are the most prescribed drug classes for pediatric gastroesophageal reflux disease (GERD).Many patients are treated with these drugs for atypical manifestations attributed to gastroesophageal reflux (GER), even in the absence of proved causal relationship. There is an impression of increase use of PPI's treatment for reflux in "clalit health services," the largest health organization in Israel. In the recent years, the medicine is given without restriction, it's not limited to pediatric gastroenterologists only, but pediatricians and family doctors. The objective of this study is to evaluate the hypothesis that exposure to PPIs during the first year of life is associated with an increased risk of developing late adverse diseases: pneumonia, asthma, AGE, IBD, celiac disease, allergic disorders, obesity, attention deficit hyperactivity disorders (ADHD), autism spectrum disorders (ASD). Methods: The study is a retrospective case-control cohort study based on a computerized database of Clalit Health Services (CHS). It includes 9844 children born between 2002-2018 and reported to complain of at least one of the symptoms (reflux/ spitting up, irritability, feeding difficulties, colics). The study population included the study group (n=4922) of children exposed to PPIs at any time prior to the first year of life and a control group (n=4922) child not exposed to PPIs who were matched to each case of the study group on age, race, socioeconomic status, and year of birth. The prevalence of late complications/diseases in the study group was compared with the prevalence of late complications/diseases diagnosis between 2002-2020 in the control group. Odds ratios and 95% confidence intervals were calculated by using logistic regression models. Results: We found that compared to the control group, children exposed to PPIs in the first year of life had an increased risk of developing several late complications/ disorders: pneumonia, asthma, various allergies (urticaria, allergic rhinitis, or allergic conjunctivitis) OR, inhalant allergies, and food allergies. In addition, they showed an increased risk of being diagnosed with ADHD or ASD, but children exposed to PPIs in the first year of life had decrease the risk of obesity by 17% (OR 0.825, 95%CI 0.697-0.976). Conclusions: We found significant associations between the use of PPIs during the first year of life and subsequent development of late complications/diseases such as respiratory diseases, allergy diseases, ADHD, and ASD. More studies are needed to prove causality and determine the mechanism behind the effect of PPIs and the development of late complications.

Keywords: acid suppressing medications, proton pump inhibitors, histamine 2 blocker, late complications, gastroesophageal reflux, gastroesophageal reflux disease, acute gastroenteritis, community acquired pneumonia, asthma, allergic diseases, obesity, inflammatory bowel diseases, ulcerative colitis, crohn disease, attention deficit hyperactivity disorders, autism spectrum disorders

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Authors: Leslie Raphael de M. Ferraz, Salvana Priscylla M. Costa, Tarcyla de A. Gomes, Giovanna Christinne R. M. Schver, Cristóvão R. da Silva, Magaly Andreza M. de Lyra, Danilo Augusto F. Fontes, Larissa A. Rolim, Amanda Carla Q. M. Vieira, Miracy M. de Albuquerque, Pedro J. Rolim-Neto

Abstract:

Efavirenz (EFV) is a drug used as first-line treatment of AIDS. However, it has poor aqueous solubility and wettability, presenting problems in the gastrointestinal tract absorption and bioavailability. One of the most promising strategies to improve the solubility is the use of solid dispersions (SD). Therefore, this study aimed to characterize SD EFZ with the polymers: PVP-K30, PVPVA 64 and SOLUPLUS in order to find an optimal formulation to compose a future pharmaceutical product for AIDS therapy. Initially, Physical Mixtures (PM) and SD with the polymers were obtained containing 10, 20, 50 and 80% of drug (w/w) by the solvent method. The best formulation obtained between the SD was selected by in vitro dissolution test. Finally, the drug-carrier system chosen, in all ratios obtained, were analyzed by the following techniques: Differential Scanning Calorimetry (DSC), polarization microscopy, Scanning Electron Microscopy (SEM) and spectrophotometry of absorption in the region of infrared (IR). From the dissolution profiles of EFV, PM and SD, the values of area Under The Curve (AUC) were calculated. The data showed that the AUC of all PM is greater than the isolated EFV, this result is derived from the hydrophilic properties of the polymers thus favoring a decrease in surface tension between the drug and the dissolution medium. In adittion, this ensures an increasing of wettability of the drug. In parallel, it was found that SD whom had higher AUC values, were those who have the greatest amount of polymer (with only 10% drug). As the amount of drug increases, it was noticed that these results either decrease or are statistically similar. The AUC values of the SD using the three different polymers, followed this decreasing order: SD PVPVA 64-EFV 10% > SD PVP-K30-EFV 10% > SD Soluplus®-EFV 10%. The DSC curves of SD’s did not show the characteristic endothermic event of drug melt process, suggesting that the EFV was converted to its amorphous state. The analysis of polarized light microscopy showed significant birefringence of the PM’s, but this was not observed in films of SD’s, thus suggesting the conversion of the drug from the crystalline to the amorphous state. In electron micrographs of all PM, independently of the percentage of the drug, the crystal structure of EFV was clearly detectable. Moreover, electron micrographs of the SD with the two polymers in different ratios investigated, we observed the presence of particles with irregular size and morphology, also occurring an extensive change in the appearance of the polymer, not being possible to differentiate the two components. IR spectra of PM corresponds to the overlapping of polymer and EFV bands indicating thereby that there is no interaction between them, unlike the spectra of all SD that showed complete disappearance of the band related to the axial deformation of the NH group of EFV. Therefore, this study was able to obtain a suitable formulation to overcome the solubility limitations of the EFV, since SD PVPVA 64-EFZ 10% was chosen as the best system in delay crystallization of the prototype, reaching higher levels of super saturation.

Keywords: characterization, dissolution, Efavirenz, solid dispersions

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