Search results for: psychotic symptoms

Authors: Izabela P. Vatanabe, Rafaela Peron, Patricia Manzine, Marcia R. Cominetti

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Introduction: Considering the increase in life expectancy of world population, there is an emerging concern in health services to allocate better care and care to elderly, through promotion, prevention and treatment of health. It has been observed that frailty syndrome is prevalent in elderly people worldwide and this complex and heterogeneous clinical syndrome consist of the presence of physical frailty associated with cognitive dysfunction, though in absence of dementia. This can be characterized by exhaustion, unintentional weight loss, decreased walking speed, weakness and low level of physical activity, in addition, each of these symptoms may be a predictor of adverse outcomes such as hospitalization, falls, functional decline, institutionalization, and death. Cognitive frailty is a recent concept in literature, which is defined as the presence of physical frailty associated with mild cognitive impairment (MCI) however in absence of dementia. This new concept has been considered as a subtype of frailty, which along with aging process and its interaction with physical frailty, accelerates functional declines and can result in poor quality of life of the elderly. MCI represents a risk factor for Alzheimer's disease (AD) in view of high conversion rate for this disease. Comorbidities and physical frailty are frequently found in AD patients and are closely related to heterogeneity and clinical manifestations of the disease. The decreased platelets ADAM10 levels in AD patients, compared to cognitively healthy subjects, matched by sex, age and education. Objective: Based on these previous results, this study aims to evaluate whether ADAM10 platelet levels of could act as a biomarker of cognitive frailty. Methods: The study was approved by Ethics Committee of Federal University of São Carlos (UFSCar) and conducted in the municipality of São Carlos, headquarters of Federal University of São Carlos (UFSCar). Biological samples of subjects were collected, analyzed and then stored in a biorepository. ADAM10 platelet levels were analyzed by western blotting technique in subjects with MCI and compared to subjects without cognitive impairment, both with and without presence of frailty. Statistical tests of association, regression and diagnostic accuracy were performed. Results: The results have shown that ADAM10/β-actin ratio is decreased in elderly individuals with cognitive frailty compared to non-frail and cognitively healthy controls. Previous studies performed by this research group, already mentioned above, demonstrated that this reduction is still higher in AD patients. Therefore, the ADAM10/β-actin ratio appears to be a potential biomarker for cognitive frailty. The results bring important contributions to an accurate diagnosis of cognitive frailty from the perspective of ADAM10 as a biomarker for this condition, however, more experiments are being conducted, using a high number of subjects, and will help to understand the role of ADAM10 as biomarker of cognitive frailty and contribute to the implementation of tools that work in the diagnosis of cognitive frailty. Such tools can be used in public policies for the diagnosis of cognitive frailty in the elderly, resulting in a more adequate planning for health teams and better quality of life for the elderly.

Keywords: ADAM10, biomarkers, cognitive frailty, elderly

Procedia PDF Downloads 200

Authors: Rupali Bhatia, Deepthi Nair, Geetika Khanna, Seema Singhal

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Introduction: Genital tract tuberculosis is a chronic disease (caused by reactivation of organisms from systemic distribution of Mycobacterium tuberculosis) that often presents with low grade symptoms and non-specific complaints. Patients with genital tuberculosis are usually young women seeking workup and treatment for infertility. Infertility is the commonest presentation due to involvement of the fallopian tubes, endometrium and ovarian damage with poor ovarian volume and reserve. The diagnosis of genital tuberculosis is difficult because of the fact that it is a silent invader of genital tract. Since tissue cannot be obtained from fallopian tubes, the diagnosis is made by isolation of bacilli from endometrial tissue obtained by endometrial biopsy curettage and/or aspiration. Problems are associated with sampling technique as well as diagnostic modality due to lack of adequate sample volumes and the segregation of the sample for various diagnostic tests resulting in non-uniform distribution of microorganisms. Moreover, lack of an efficient sampling technique universally applicable for all specific diagnostic tests contributes to the diagnostic challenges. Endometrial sampling plays a key role in accurate diagnosis of female genital tuberculosis. It may be done by 2 methods viz. endometrial curettage and endometrial aspiration. Both endometrial curettage and aspirate have their own limitations as curettage picks up strip of the endometrium from one of the walls of the uterine cavity including tubal osteal areas whereas aspirate obtains total tissue with exfoliated cells present in the secretory fluid of the endometrial cavity. Further, sparse and uneven distribution of the bacilli remains a major factor contributing to the limitations of the techniques. The sample that is obtained by either technique is subjected to histopathological examination, AFB staining, culture and PCR. Aim: Comparison of the sampling techniques viz. endometrial biopsy curettage and endometrial aspiration using different laboratory methods of histopathology, cytology, microbiology and molecular biology. Method: In a hospital based observational study, 75 Indian females suspected of genital tuberculosis were selected on the basis of inclusion criteria. The women underwent endometrial tissue sampling using Novaks biopsy curette and Karmans cannula. One part of the specimen obtained was sent in formalin solution for histopathological testing and another part was sent in normal saline for acid fast bacilli smear, culture and polymerase chain reaction. The results so obtained were correlated using coefficient of correlation and chi square test. Result: Concordance of results showed moderate agreement between both the sampling techniques. Among HPE, AFB and PCR, maximum sensitivity was observed for PCR, though the specificity was not as high as other techniques. Conclusion: Statistically no significant difference was observed between the results obtained by the two sampling techniques. Therefore, one may use either EA or EB to obtain endometrial samples and avoid multiple sampling as both the techniques are equally efficient in diagnosing genital tuberculosis by HPE, AFB, culture or PCR.

Keywords: acid fast bacilli (AFB), histopatholgy examination (HPE), polymerase chain reaction (PCR), endometrial biopsy curettage

Procedia PDF Downloads 305

Authors: Staci McGill, Morgan Hayes, Robert Coleman, Kimberly Tumlin

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The interaction and relationships between horses and humans have been shown to be positive for physical, mental, and emotional wellbeing, however equine spaces where these interactions occur do include some environmental risks. There are 1.7 million jobs associated with the equine industry in the United States in addition to recreational riders, owners, and volunteers who interact with horses for substantial amounts of time daily inside built structures. One specialized facility, an “indoor arena” is a semi-indoor structure used for exercising horses and exhibiting skills during competitive events. Typically, indoor arenas have a sand or sand mixture as the footing or surface over which the horse travels, and increasingly, silica sand is being recommended due to its durable nature. It was previously identified in a semi-qualitative survey that the majority of individuals using indoor arenas have environmental concerns with dust. 27% (90/333) of respondents reported respiratory issues or allergy-like symptoms while riding with 21.6% (71/329) of respondents reporting these issues while standing on the ground observing or teaching. Frequent headaches and/or lightheadedness was reported in 9.9% (33/333) of respondents while riding and in 4.3% 14/329 while on the ground. Horse respiratory health is also negatively impacted with 58% (194/333) of respondents indicating horses cough during or after time in the indoor arena. Instructors who spent time in indoor arenas self-reported more respiratory issues than those individuals who identified as smokers, highlighting the health relevance of understanding these unique structures. To further elucidate environmental concerns and self-reported health issues, 35 facility assessments were conducted in a cross-sectional sampling design in the states of Kentucky and Ohio (USA). Data, including air speeds, were collected in a grid fashion at 15 points within the indoor arenas and then mapped spatially using krigging in ARCGIS. From the spatial maps, standard variances were obtained and differences were analyzed using multivariant analysis of variances (MANOVA) and analysis of variances (ANOVA). There were no differences for the variance of the air speeds in the spaces for facility orientation, presence and type of roof ventilation, climate control systems, amount of openings, or use of fans. Variability of the air speeds in the indoor arenas was 0.25 or less. Further analysis yielded that average air speeds within the indoor arenas were lower than 100 ft/min (0.51 m/s) which is considered still air in other animal facilities. The lack of air movement means that dust clearance is reliant on particle size and weight rather than ventilation. While further work on respirable dust is necessary, this characterization of the semi-indoor environment where animals and humans interact indicates insufficient air flow to eliminate or reduce respiratory hazards. Finally, engineering solutions to address air movement deficiencies within indoor arenas or mitigate particulate matter are critical to ensuring exposures do not lead to adverse health outcomes for equine professionals, volunteers, participants, and horses within these spaces.

Keywords: equine, indoor arena, ventilation, particulate matter, respiratory health

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Authors: Merve Begum Terzi, Orhan Arikan, Adnan Abaci, Mustafa Candemir

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Acute myocardial infarction is a major cause of death in the world. Therefore, its fast and reliable diagnosis is a major clinical need. ECG is the most important diagnostic methodology which is used to make decisions about the management of the cardiovascular diseases. In patients with acute myocardial ischemia, temporary chest pains together with changes in ST segment and T wave of ECG occur shortly before the start of myocardial infarction. In this study, a technique which detects changes in ST/T sections of ECG is developed for the early diagnosis of acute myocardial ischemia. For this purpose, a database of real ECG recordings that contains a set of records from 75 patients presenting symptoms of chest pain who underwent elective percutaneous coronary intervention (PCI) is constituted. 12-lead ECG’s of the patients were recorded before and during the PCI procedure. Two ECG epochs, which are the pre-inflation ECG which is acquired before any catheter insertion and the occlusion ECG which is acquired during balloon inflation, are analyzed for each patient. By using pre-inflation and occlusion recordings, ECG features that are critical in the detection of acute myocardial ischemia are identified and the most discriminative features for the detection of acute myocardial ischemia are extracted. A classification technique based on support vector machine (SVM) approach operating with linear and radial basis function (RBF) kernels to detect ischemic events by using ST-T derived joint features from non-ischemic and ischemic states of the patients is developed. The dataset is randomly divided into training and testing sets and the training set is used to optimize SVM hyperparameters by using grid-search method and 10fold cross-validation. SVMs are designed specifically for each patient by tuning the kernel parameters in order to obtain the optimal classification performance results. As a result of implementing the developed classification technique to real ECG recordings, it is shown that the proposed technique provides highly reliable detections of the anomalies in ECG signals. Furthermore, to develop a detection technique that can be used in the absence of ECG recording obtained during healthy stage, the detection of acute myocardial ischemia based on ECG recordings of the patients obtained during ischemia is also investigated. For this purpose, a Gaussian mixture model (GMM) is used to represent the joint pdf of the most discriminating ECG features of myocardial ischemia. Then, a Neyman-Pearson type of approach is developed to provide detection of outliers that would correspond to acute myocardial ischemia. Neyman – Pearson decision strategy is used by computing the average log likelihood values of ECG segments and comparing them with a range of different threshold values. For different discrimination threshold values and number of ECG segments, probability of detection and probability of false alarm values are computed, and the corresponding ROC curves are obtained. The results indicate that increasing number of ECG segments provide higher performance for GMM based classification. Moreover, the comparison between the performances of SVM and GMM based classification showed that SVM provides higher classification performance results over ECG recordings of considerable number of patients.

Keywords: ECG classification, Gaussian mixture model, Neyman–Pearson approach, support vector machine

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Authors: Bernice Jeanne Lottering, Yi-Wen Lin

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Introduction: Chronic pain has a definitive lack of objective parameters in the measurement and treatment efficacy of diseases such as Fibromyalgia (FM). Persistent widespread pain and generalized tenderness are the characteristic symptoms affecting a large majority of the global population, particularly females. This disease has indicated a refractory tendency to conventional treatment ventures, largely resultant from a lack of etiological and pathogenic understanding of the disease development. Emerging evidence indicates that the central nervous system (CNS) plays a critical role in the amplification of pain signals and the neurotransmitters associated therewith. Various stimuli have been found to activate the channels existent on nociceptor terminals, thereby actuating nociceptive impulses along the pain pathways. The transient receptor potential vanalloid 1 (TRPV1) channel functions as a molecular integrator for numerous sensory inputs, such as nociception, and was explored in the current study. Current intervention approaches face a multitude challenges, ranging from effective therapeutic interventions to the limitation of pathognomonic criteria resultant from incomplete understanding and partial evidence on the mechanisms of action of FM. It remains unclear whether electroacupuncture (EA) plays an integral role in the functioning of the TRPV1 pathway, and whether or not it can reduce the chronic pain induced by FM. Aims: The aim of this study was to explore the mechanisms underlying the activation and modulation of the TRPV1 channel pathway in a cold stress model of FM applied to a murine model. Furthermore, the effect of EA in the treatment of mechanical and thermal pain, as expressed in FM was also to be investigated. Methods: 18 C57BL/6 wild type and 6 TRPV1 knockout (KO) mice, aged 8-12 weeks, were exposed to an intermittent cold stress-induced fibromyalgia-like pain model, with or without EA treatment at ZusanLi ST36 (2Hz/20min) on day 3 to 5. Von Frey and Hargreaves behaviour tests were implemented in order to analyze the mechanical and thermal pain thresholds on day 0, 3 and 5 in control group (C), FM group (FM), FM mice with EA treated group (FM + EA) and FM in KO group. Results: An increase in mechanical and thermal hyperalgesia was observed in the FM, EA and KO groups when compared to the control group. This initial increase was reduced in the EA group, which directs focus at the treatment efficacy of EA in nociceptive sensitization, and the analgesic effect EA has attenuating FM associated pain. Discussion: An increase in the nociceptive sensitization was observed through higher withdrawal thresholds in the von Frey mechanical test and the Hargreaves thermal test. TRPV1 function in mice has been scientifically associated with these nociceptive conduits, and the increased behaviour test results suggest that TRPV1 upregulation is central to the FM induced hyperalgesia. This data was supported by the decrease in sensitivity observed in results of the TRPV1 KO group. Moreover, the treatment of EA showed a decrease in this FM induced nociceptive sensitization, suggesting TRPV1 upregulation and overexpression can be attenuated by EA at bilateral ST36. This evidence compellingly implies that the analgesic effect of EA is associated with TRPV1 downregulation.

Keywords: fibromyalgia, electroacupuncture, TRPV1, nociception

Procedia PDF Downloads 117

Authors: A. F. C. Nassar, D. K. Tessler, L. Okuda, C. Del Fava, D. P. Chiebao, A. H. C. N. Romaldini, A. P. Alvim, M. J. Sanchez-Vazquez, M. S. Rosa, J. C. Pompei, R. Harakava, M. C. S. Araujo, G. H. F. Marques, E. M. Pituco

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Glanders is a zoonotic disease of Equidae caused by the bacterium Burkholderia mallei presented in acute or chronic clinical forms with inflammatory nodules in the respiratory tract, lymphangitis and caseous lymph nodes. There is not a treatment with veterinary drugs to this life-threatening disease; thus, its occurrence must be notified to official animal health services and any infected animal must be eliminated. This study aims to detect B. mallei from horses euthanized in outbreaks of glanders in Brazil, providing a better understanding of the bacterial characteristics and determine a proper protocol for isolation. The work was carried out with the collaboration of the Ministry of Agriculture and the Sao Paulo State Animal Health Department, while its procedures were approved by the Committee of Ethics in Animal Experimentation from the Instituto Biologico (CETEA n°156/2017). To the present time, 16 horses from farms with outbreaks of glanders detected by complement fixation test (CFT) serology method were analyzed. During the necropsy, samples of possibly affected organs (lymph nodes, lungs, heart, liver, spleen, kidneys and trachea) were collected for bacterial isolation, molecular tests and pathology. Isolation was performed using two enriched mediums, a potato infusion agar with 5% sheep blood, 4% glycerol and antibiotics (penicilin100U/ mL), and another with the same ingredients except the antibiotic. A PCR protocol was modified for this study using primers design to identify a region of the Flip gen of B. mallei. Thru isolation, 12.5% (2/16) animals were confirmed positive using only the enriched medium with antibiotic and confirmed by PCR: from mediastinal and submandibular lymph nodes and lungs in one animal and from mediastinal lymph node in the other. The detection of the bacterium using PCR showed positivity of 100% (16/16) horses from 144 samples of organs. Pathology macroscopic lesions observed were catarrhal nasal discharge, fetlock ulcers, emaciation, lymphangitis in limbs, suppurative lymphangitis, lymph node enlargement, star shaped liver, and spleen scars, adherence of the renal capsule, pulmonary hemorrhage, and miliary nodules. Microscopic lesions were suppurative bronchopneumonia with microabscesses and Langhans giant cells in lungs; lymph nodes with abscesses and intense lymphoid reaction; hemosiderosis and abscesses in spleen. Positive samples on PCR will be sequenced later and analyzed comparing with previous records in the literature. A throughout description of the recent acute cases of glanders occurring in Brazil and characterization of the bacterium related will contribute to advances in the knowledge of the pathogenicity, clinical symptoms, and epidemiology of this zoonotic disease. Acknowledgment: This project is sponsored by FAPESP.

Keywords: equines, bacterial isolation, zoonosis, PCR, pathology

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Authors: Milada Krejci, Martin Hill, Vaclav Hosek, Dobroslava Jandova, Jiri Kajzar, Pavel Blaha

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The paper declares effects of exercise intervention of the research project “Basic research of balance changes in seniors”, granted by the Czech Science Foundation. The objective of the presented study is to define predictors, which influence bio-psycho-social consequences and effects of balance ability in senior 65 years old and above. We focused on the Fall-Efficacy Scale changes evaluation in seniors. Comprehensive hypothesis of the project declares, that motion uncertainty (dyskinesia) can negatively affect the well-being of a senior in bio-psycho-social context. In total, random selection and testing of 100 seniors (30 males, 70 females) from Prague and Central Bohemian region was provided. The sample was divided by stratified random selection into experimental and control groups, who underwent input and output testing. For diagnostics the methods of Medical Anamnesis, Functional anthropological examinations, Tinetti Balance Assessment Tool, SF-36 Health Survey, Anamnestic comparative self-assessment scale were used. Intervention method called "Life in Balance" based on yoga techniques was applied in four-week cycle. Results of multivariate regression were verified by repeated measures ANOVA: subject factor, phase of intervention (between-subject factor), body fluid (within-subject factor) and phase of intervention × body fluid interaction). ANOVA was performed with a repetition involving the factors of subjects, experimental/control group, phase of intervention (independent variable), and x phase interaction followed by Bonferroni multiple comparison assays with a test strength of at least 0.8 on the probability level p < 0.05. In the paper results of the first-year investigation of the three years running project are analysed. Results of balance tests confirmed no significant difference between females and males in pre-test. Significant improvements in balance and walking ability were observed in experimental group in females comparing to males (F = 128.4, p < 0.001). In the females control group, there was no significant change in post- test, while in the female experimental group positive changes in posture and spine flexibility in post-tests were found. It seems that females even in senior age react better to incentives of intervention in balance and spine flexibility. On the base of results analyses, we can declare the significant improvement in social balance markers after intervention in the experimental group (F = 10.5, p < 0.001). In average, seniors are used to take four drugs daily. Number of drugs can contribute to allergy symptoms and balance problems. It can be concluded that static balance and walking ability of seniors according Tinetti Balance scale correlate significantly with psychic and social monitored markers.

Keywords: exercises, balance, seniors 65+, health, mental and social balance

Procedia PDF Downloads 101

Authors: Arti Singh, Carolyn Jenkins, Oyedunni S. Arulogun, Mayowa O. Owolabi, Fred S. Sarfo, Bruce Ovbiagele, Enzinne Sylvia

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Background: Stroke, the leading cause of adult-onset disability and the second leading cause of death, is a major public health concern particularly pertinent in Sub-Saharan Africa (SSA), where nearly 80% of all global stroke mortalities occur. The Stroke Investigative Research and Education Network (SIREN) seeks to comprehensively characterize the genomic, sociocultural, economic, and behavioral risk factors for stroke and to build effective teams for research to address and decrease the burden of stroke and other non communicable diseases in SSA. One of the first steps to address this goal was to effectively engage the communities that suffer the high burden of disease in SSA. This study describes how the SIREN project engaged six sites in Ghana and Nigeria over the past three years, describing the community engagement activities that have arisen since inception. Aim: The aim of community engagement (CE) within SIREN is to elucidate information about knowledge, attitudes, beliefs, and practices (KABP) about stroke and its risk factors from individuals of African ancestry in SSA, and to educate the community about stroke and ways to decrease disabilities and deaths from stroke using socioculturally appropriate messaging and messengers. Methods: Community Advisory Board (CABs), Focus Group Discussions (FGDs) and community outreach programs. Results: 27 FGDs with 168 participants including community heads, religious leaders, health professionals and individuals with stroke among others, were conducted, and over 60 CE outreaches have been conducted within the SIREN performance sites. Over 5,900 individuals have received education on cardiovascular risk factors and about 5,000 have been screened for cardiovascular risk factors during the outreaches. FGDs and outreach programs indicate that knowledge of stroke, as well as risk factors and follow-up evidence-based care is limited and often late. Other findings include: 1) Most recognize hypertension as a major risk factor for stroke. 2) About 50% report that stroke is hereditary and about 20% do not know organs affected by stroke. 3) More than 95% willing to participate in genetic testing research and about 85% willing to pay for testing and recommend the test to others. 4) Almost all indicated that genetic testing could help health providers better treat stroke and help scientists better understand the causes of stroke. The CABs provided stakeholder input into SIREN activities and facilitated collaborations among investigators, community members and stakeholders. Conclusion: The CE core within SIREN is a first-of-its kind public outreach engagement initiative to evaluate and address perceptions about stroke and genomics by patients, caregivers, and local leaders in SSA and has implications as a model for assessment in other high-stroke risk populations. SIREN’s CE program uses best practices to build capacity for community-engaged research, accelerate integration of research findings into practice and strengthen dynamic community-academic partnerships within our communities. CE has had several major successes over the past three years including our multi-site collaboration examining the KABP about stroke (symptoms, risk factors, burden) and genetic testing across SSA.

Keywords: community advisory board, community engagement, focus groups, outreach, SSA, stroke

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Authors: Allison Herlene Du Plessis, Dalena (R.M.) Van Rooyen, Wilma Ten Ham-Baloyi, Sihaam Jardien-Baboo

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Introduction: Women die in pregnancy and childbirth for five main reasons—severe bleeding, infections, unsafe abortions, hypertensive disorders (pre-eclampsia and eclampsia), and medical complications including cardiac disease, diabetes, or HIV/AIDS complicated by pregnancy. In 2015, WHO classified sepsis as the third highest cause for maternal mortalities in the world. Chorioamnionitis is a clinical syndrome of intrauterine infection during any stage of the pregnancy and it refers to ascending bacteria from the vaginal canal up into the uterus, causing infection. While the incidence rates for chorioamnionitis are not well documented, complications related to chorioamnionitis are well documented and midwives still struggle to identify this condition in time due to its complex nature. Few diagnostic methods are available in public health services, due to escalated laboratory costs. Often the affordable biomarkers, such as C-reactive protein CRP, full blood count (FBC) and WBC, have low significance in diagnosing chorioamnionitis. A lack of screening impacts on effective and timeous management of chorioamnionitis, and early identification and management of risks could help to prevent neonatal complications and reduce the subsequent series of morbidities and healthcare costs of infants who are health foci of perinatal infections. Objective: This integrative literature review provides an overview of current best research evidence on the screening of women at risk for chorioamnionitis. Design: An integrative literature review was conducted using a systematic electronic literature search through EBSCOhost, Cochrane Online, Wiley Online, PubMed, Scopus and Google. Guidelines, research studies, and reports in English related to chorioamnionitis from 2008 up until 2020 were included in the study. Findings: After critical appraisal, 31 articles were included. More than one third (67%) of the literature included ranked on the three highest levels of evidence (Level I, II and III). Data extracted regarding screening for chorioamnionitis was synthesized into four themes, namely: screening by clinical signs and symptoms, screening by causative factors of chorioamnionitis, screening of obstetric history, and essential biomarkers to diagnose chorioamnionitis. Key conclusions: There are factors that can be used by midwives to identify women at risk for chorioamnionitis. However, there are a paucity of established sociological, epidemiological and behavioral factors to screen this population. Several biomarkers are available to diagnose chorioamnionitis. Increased Interleukin-6 in amniotic fluid is the better indicator and strongest predictor of histological chorioamnionitis, whereas the available rapid matrix-metalloproteinase-8 test requires further testing. Maternal white blood cells count (WBC) has shown poor selectivity and sensitivity, and C-reactive protein (CRP) thresholds varied among studies and are not ideal for conclusive diagnosis of subclinical chorioamnionitis. Implications for practice: Screening of women at risk for chorioamnionitis by health care providers providing care for pregnant women, including midwives, is important for diagnosis and management before complications arise, particularly in resource-constraint settings.

Keywords: chorioamnionitis, guidelines, best evidence, screening, diagnosis, pregnant women

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Authors: Irene T. Ho

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Students with Autism Spectrum Disorder (ASD) studying in mainstream schools often face difficulties adjusting to school life and teachers often find it challenging to meet the needs of these students. The Hong Kong Jockey Club Autism Support Network (JC A-Connect) is an initiative launched in 2015 to enhance support for students with ASD as well as their families and schools. The School Support Programme of the Project aims at building the capacity of schools to provide quality education for these students. The present report provides a summary of the main features of the support model and the related evaluation results. The school support model was conceptualized in response to four observed needs: (1) inadequate teacher expertise in dealing with the related challenges, (2) the need to promote evidence-based practices in schools, (3) less than satisfactory home-school collaboration and whole-school participation, and (4) lack of concerted effort by different parties involved in providing support to schools. The resulting model had partnership and capacity building as two guiding tenets for the School Support Programme. There were two levels of partnership promoted in the project. At the programme support level, a platform that enables effective collaboration among major stakeholders was established, including the funding body that provides the necessary resources, the Education Bureau that helps to engage schools, university experts who provide professional leadership and research support, as well as non-governmental organization (NGO) professionals who provide services to the schools. At the programme implementation level, tripartite collaboration among teachers, parents and professionals was emphasized. This notion of partnership permeated efforts at capacity building targeting students with ASD, school personnel, parents and peers. During 2015 to 2018, school-based programmes were implemented in over 400 primary and secondary schools with the following features: (1) spiral Tier 2 (group) training for students with ASD to enhance their adaptive skills, led by professionals but with strong teacher involvement to promote transfer of knowledge and skills; (2) supplementary programmes for teachers, parents and peers to enhance their capability to support students with ASD; and (3) efforts at promoting continuing or transfer of learning, on the part of both students and teachers, to Tier 1 (classroom practice) and Tier 3 (individual training) contexts. Over 5,000 students participated in the Programme, representing about 50% of students diagnosed with ASD in mainstream public sector schools in Hong Kong. Results showed that the Programme was effective in helping students improve to various extents at three levels: achievement of specific training goals, improvement in adaptive skills in school, and change in ASD symptoms. The sense of competence of teachers and parents in dealing with ASD-related issues, measured by self-report rating scales, was also significantly enhanced. Moreover, effects on enhancing the school system to provide support for students with ASD, assessed according to indicators of inclusive education, were seen. The process and results of this Programme illustrate how obstacles to inclusive education for students with ASD could be overcome by strengthening the necessary partnerships and building the required capabilities of all parties concerned.

Keywords: autism, school support, skills training, teacher development, three-tier model

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Authors: Vijay Kumar, G. K. Grewal, Prasad S. Burange

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India is one of the largest cultivators of cotton in the world. Among the various constraints, insect pests are posing a major hurdle to the success of cotton cultivation. Various bollworms, including the pink bollworm, Pectinophora gossypiella (Saunders), cause serious losses in India, China, Pakistan, Egypt, Brazil, tropical America, and Africa, etc. Bt cotton cultivars having Cry genes were introduced in India in 2002 (Cry1Ac) and 2006 (Cry1Ac+ Cry2Ab) for control of American, spotted, and pink bollworms. Pink bollworm (PBW) larvae infest flowers, squares, and bolls. Larva burrows into flowers and bolls to feed on pollen and seeds, respectively. It has a shorter lifecycle and more generations per year, so it develops resistance more quickly than other bollworms. Further, it has cryptic feeding sites, i.e., flowers and bolls/seeds, so it is not exposed to harsh environmental fluctuations and insecticidal applications. The cry toxin concentration is low in its feeding sites, i.e., seeds and flowers of cotton. The use of insecticide and Bt cotton is the primary control measure that has been successful in limiting the damage of PBW. But with the passage of time, it has developed resistance against insecticides and Bt cotton. However, the use of insecticides increases chemical control costs while causing secondary pest problems and environmental pollution. Extensive research has indicated that monitoring and control measures such as biological, cultural, chemical, and host plant resistance methods can be integrated for effective PBW management. The potential of various biological control organisms needs to be explored. The impact of transgenic cotton on non-target organisms, particularly natural enemies, which play an important role in pest control, is still being debated. According to some authors, Bt crops have a negative impact on natural enemies, particularly parasitoids. An experiment was carried out in the Integrated Pest Management Laboratory of the Department of Entomology, Punjab Agricultural University, Ludhiana, Punjab, India, to study the natural parasitization of PBW on Bt cotton in 2022. A large population of larvae of PBW were kept individually in plastic containers and fed with cotton bolls until the emergence of a parasitoid cocoon. The first cocoon of the parasitoid was observed on October 25, 2022. Symptoms of parasitization were never seen on larvae. Larvae stopped feeding and became inactive before the emergence of parasitoids for pupation. Grub makes its way out of larvae by making a hole in the integument, and immediately after coming out, it spins the cocoon. The adult parasitoid emerged from the cocoon after eight days. The parasitoids that emerged from the cocoon were identified as Cotesia (Braconidae: Hymenoptera) based on the features of the adult. Out of 475 larvae of PBW, 87 were parasitized, with 18.31% of parasitization. Out of these, 6.73% were first instar, 10.52% were second instar, and 1.05% were third instar larvae of PBW. No parasitization was observed in fourth instar larvae. Parasitoids were observed during the fag end of cropping season and mostly on the earlier instars. It is concluded that the potential of Cotesia may be explored as a biological control agent against PBW, which is safer to human beings, environment and non-taraltoget organisms.

Keywords: biocontrol, Bt cotton, Cotesia, Pectinophora gossypiella

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Authors: Aurora Sheehy, Caitlin Prince

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Within current orthodox medical protocols, trauma and mental health issues are deemed to reside within the realm of cognitive or psychological therapists and are marginalised in these areas, in part due to limited drugs option available, mostly manipulating neurotransmitters or sedating patients to reduce symptoms. By contrast, this research presents examples from the clinical practice of how trauma can be assessed and treated physiologically. Adverse Childhood Experiences (ACEs) are a tally of different types of abuse and neglect. It has been used as a measurable and reliable predictor of the likelihood of the development of autoimmune disease. It is a direct way to demonstrate reliably the health impact of traumatic life experiences. A second assessment tool is Allostatic Load, which refers to the cumulative effects that chronic stress has on mental and physical health. It records the decline of an individual’s physiological capacity to cope with their experience. It uses a specific grouping of serum testing and physical measures. It includes an assessment of neuroendocrine, cardiovascular, immune and metabolic systems. Allostatic load demonstrates the health impact that trauma has throughout the body. It forms part of an initial intake assessment in clinical practice and could also be used in research to evaluate treatment. Examining medicinal plants for their physiological, neurological and somatic effects through the lens of Polyvagal theory offers new opportunities for trauma treatments. In situations where Polyvagal theory recommends activities and exercises to enable parasympathetic activation, many herbs that affect Effector Memory T (TEM) cells also enact these responses. Traditional or Indigenous European herbs show the potential to support the polyvagal tone, through multiple mechanisms. As the ventral vagal nerve reaches almost every major organ, plants that have actions on these tissues can be understood via their polyvagal actions, such as monoterpenes as agents to improve respiratory vagal tone, cyanogenic glycosides to reset polyvagal tone, volatile oils rich in phenyl methyl esters improve both sympathetic and parasympathetic tone, bitters activate gut function and can strongly promote parasympathetic regulation. Auricular Acupuncture uses a system of somatotopic mapping of the auricular surface overlaid with an image of an inverted foetus with each body organ and system featured. Given that the concha of the auricle is the only place on the body where the Vagus Nerve neurons reach the surface of the skin, several investigators have evaluated non-invasive, transcutaneous electrical nerve stimulation (TENS) at auricular points. Drawn from an interdisciplinary evidence base and developed through clinical practice, these assessment and treatment tools are examples of practitioners in the field innovating out of necessity for the best outcomes for patients. This paper draws on case studies to direct future research.

Keywords: polyvagal, auricular acupuncture, trauma, herbs

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Authors: Vitaliy Petrov, Natalia Shusharina, Vitaliy Kasymov, Maksim Patrushev, Evgeny Bogdanov

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The leading worldwide death reasons are ischemic heart disease and other cardiovascular illnesses. Generally, the common symptom is high blood pressure. Long-time blood pressure control is very important for the prophylaxis, correct diagnosis and timely therapy. Non-invasive methods which are based on Korotkoff sounds are impossible to apply often and for a long time. Implantable devices can combine longtime monitoring with high accuracy of measurements. The main purpose of this work is to create a real-time monitoring system for decreasing the death rate from cardiovascular diseases. These days implantable electronic devices began to play an important role in medicine. Usually implantable devices consist of a transmitter, powering which could be wireless with a special made battery and measurement circuit. Common problems in making implantable devices are short lifetime of the battery, big size and biocompatibility. In these work, blood pressure measure will be the focus because it’s one of the main symptoms of cardiovascular diseases. Our device will consist of three parts: the implantable pressure sensor, external transmitter and automated workstation in a hospital. The Implantable part of pressure sensors could be based on piezoresistive or capacitive technologies. Both sensors have some advantages and some limitations. The Developed circuit is based on a small capacitive sensor which is made of the technology of microelectromechanical systems (MEMS). The Capacitive sensor can provide high sensitivity, low power consumption and minimum hysteresis compared to the piezoresistive sensor. For this device, it was selected the oscillator-based circuit where frequency depends from the capacitance of sensor hence from capacitance one can calculate pressure. The external device (transmitter) used for wireless charging and signal transmission. Some implant devices for these applications are passive, the external device sends radio wave signal on internal LC circuit device. The external device gets reflected the signal from the implant and from a change of frequency is possible to calculate changing of capacitance and then blood pressure. However, this method has some disadvantages, such as the patient position dependence and static using. Developed implantable device doesn’t have these disadvantages and sends blood pressure data to the external part in real-time. The external device continuously sends information about blood pressure to hospital cloud service for analysis by a physician. Doctor’s automated workstation at the hospital also acts as a dashboard, which displays actual medical data of patients (which require attention) and stores it in cloud service. Usually, critical heart conditions occur few hours before heart attack but the device is able to send an alarm signal to the hospital for an early action of medical service. The system was tested with wireless charging and data transmission. These results can be used for ASIC design for MEMS pressure sensor.

Keywords: MEMS sensor, RF power, wireless data, oscillator-based circuit

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Authors: Monika Sobolewska, Aleksandra Majchrzak, Bartlomiej Chojnacki, Katarzyna Baruch, Adam Pilch

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The main purpose of the study is to perform the measurement and analysis of noise harmfulness in public utility facilities. The World Health Organization reports that the number of people suffering from hearing impairment is constantly increasing. The most alarming is the number of young people occurring in the statistics. The majority of scientific research in the field of hearing protection and noise prevention concern industrial and road traffic noise as the source of health problems. As the result, corresponding standards and regulations defining noise level limits are enforced. However, there is another field uncovered by profound research – leisure time. Public utility facilities such as clubs, shopping malls, sport facilities or concert halls – they all generate high-level noise, being out of proper juridical control. Among European Union Member States, the highest legislative act concerning noise prevention is the Environmental Noise Directive 2002/49/EC. However, it omits the problem discussed above and even for traffic, railway and aircraft noise it does not set limits or target values, leaving these issues to the discretion of the Member State authorities. Without explicit and uniform regulations, noise level control at places designed for relaxation and entertainment is often in the responsibility of people having little knowledge of hearing protection, unaware of the risk the noise pollution poses. Exposure to high sound levels in clubs, cinemas, at concerts and sports events may result in a progressive hearing loss, especially among young people, being the main target group of such facilities and events. The first step to change this situation and to raise the general awareness is to perform reliable measurements the results of which will emphasize the significance of the problem. This project presents the results of more than hundred measurements, performed in most types of public utility facilities in Poland. As the most suitable measuring instrument for such a research, personal noise dosimeters were used to collect the data. Each measurement is presented in the form of numerical results including equivalent and peak sound pressure levels and a detailed description considering the type of the sound source, size and furnishing of the room and the subjective sound level evaluation. In the absence of a straight reference point for the interpretation of the data, the limits specified in EU Directive 2003/10/EC were used for comparison. They set the maximum sound level values for workers in relation to their working time length. The analysis of the examined problem leads to the conclusion that during leisure time, people are exposed to noise levels significantly exceeding safe values. As the hearing problems are gradually progressing, most people underplay the problem, ignoring the first symptoms. Therefore, an effort has to be made to specify the noise regulations for public utility facilities. Without any action, in the foreseeable future the majority of Europeans will be dealing with serious hearing damage, which will have a negative impact on the whole societies.

Keywords: hearing protection, noise level limits, noise prevention, noise regulations, public utility facilities

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Authors: B. S. Premalatha, Kausalya Sahani

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Background: Glomus jugulare tumors arise within the jugular foramen and are commonly seen in females particularly on the left side. Surgical excision of the tumor may cause lower cranial nerve deficits. Cranial nerve involvement produces hoarseness of voice, slurred speech, and dysphagia along with other physical symptoms, thereby affecting the quality of life of individuals. Though oncological clearance is mainly emphasized on while treating these individuals, little importance is given to their communication, voice and swallowing problems, which play a crucial part in daily functioning. Objective: To examine the functions of voice, speech and swallowing outcomes of the subjects, following excision of glomus jugulare tumor. Methods: Two female subjects aged 56 and 62 years had come with a complaint of change in voice, inability to swallow and reduced clarity of speech following surgery for left glomus jugulare tumor were participants of the study. Their surgical information revealed multiple cranial nerve palsies involving the left facial, left superior and recurrent branches of the vagus nerve, left pharyngeal, left soft palate, left hypoglossal and vestibular nerves. Functional outcomes of voice, speech and swallowing were evaluated by perceptual and objective assessment procedures. Assessment included the examination of oral structures and functions, dysarthria by Frenchey dysarthria assessment, cranial nerve functions and swallowing functions. MDVP and Dr. Speech software were used to evaluate acoustic parameters of voice and quality of voice respectively. Results: The study revealed that both the subjects, subsequent to excision of glomus jugulare tumor, showed a varied picture of affected oral structure and functions, articulation, voice and swallowing functions. The cranial nerve assessment showed impairment of the vagus, hypoglossal, facial and glossopharyngeal nerves. Voice examination indicated vocal cord paralysis associated with breathy quality of voice, weak voluntary cough, reduced pitch and loudness range, and poor respiratory support. Perturbation parameters as jitter, shimmer were affected along with s/z ratio indicative of voice fold pathology. Reduced MPD(Maximum Phonation Duration) of vowels indicated that disturbed coordination between respiratory and laryngeal systems. Hypernasality was found to be a prominent feature which reduced speech intelligibility. Imprecise articulation was seen in both the subjects as the hypoglossal nerve was affected following surgery. Injury to vagus, hypoglossal, gloss pharyngeal and facial nerves disturbed the function of swallowing. All the phases of swallow were affected. Aspiration was observed before and during the swallow, confirming the oropharyngeal dysphagia. All the subsystems were affected as per Frenchey Dysarthria Assessment signifying the diagnosis of flaccid dysarthria. Conclusion: There is an observable communication and swallowing difficulty seen following excision of glomus jugulare tumor. Even with complete resection, extensive rehabilitation may be necessary due to significant lower cranial nerve dysfunction. The finding of the present study stresses the need for involvement of as speech and swallowing therapist for pre-operative counseling and assessment of functional outcomes.

Keywords: functional outcome, glomus jugulare tumor excision, multiple cranial nerve impairment, speech and swallowing

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Authors: Qudsiya Baig

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Empathy yields an unparalleled therapeutic value within patient physician interactions. Medical research is inundated with evidence to support that a physician’s ability to empathise with patients leads to a greater willingness to report symptoms, an improvement in diagnostic accuracy and safety, and a better adherence and satisfaction with treatment plans. Furthermore, the Institute of Medicine states that empathy leads to a more patient-centred care, which is one of the six main goals of a 21st century health system. However, there is a paradox between the theoretical significance of empathy and its presence, or lack thereof, in clinical practice. Recent studies have reported that empathy declines amongst students and physicians over time. The three most impactful contributors to this decline are: (1) disagreements over the definitions of empathy making it difficult to implement it into practice (2) poor consideration or regulation of empathy leading to burnout and thus, abandonment altogether, and (3) the lack of diversity in the curriculum and the influence of medical culture, which prioritises science over patient experience, limiting some physicians from using ‘too much’ empathy in the fear of losing clinical objectivity. These issues were investigated by conducting a fully inductive thematic narrative analysis of patient narratives in the UK to evaluate the behaviours and attitudes that patients associate with empathy. The principal enquiries underpinning this study included uncovering the factors that affected experience of empathy within provider-patient interactions and to analyse their effects on patient care. This research contributes uniquely to this discourse by examining the phenomenon of empathy directly from patients’ experiences, which were systematically extracted from a repository of online patient narratives of care titled ‘CareOpinion UK’. Narrative analysis was specifically chosen as the methodology to examine narratives from a phenomenological lens to focus on the particularity and context of each story. By enquiring beyond the superficial who-whatwhere, the study of narratives prescribed meaning to illness by highlighting the everyday reality of patients who face the exigent life circumstances created by suffering, disability, and the threat of life. The following six themes were found to be the most impactful in influencing the experience of empathy: dismissive behaviours, judgmental attitudes, undermining patients’ pain or concerns, holistic care and failures and successes of communication or language. For each theme there were overarching themes relating to either a failure to understand the patient’s perspective or a success in taking a person-centred approach. An in-depth analysis revealed that a lack of empathy was greatly associated with an emotive-cognitive imbalance, which disengaged physicians with their patients’ emotions. This study hereby concludes that competent providers require a combination of knowledge, skills, and more importantly empathic attitudes to help create a context for effective care. The crucial elements of that context involve (a) identifying empathy clues within interactions to engage with patients’ situations, (b) attributing a perspective to the patient through perspective-taking and (c) adapting behaviour and communication according to patient’s individual needs. Empathy underpins that context, as does an appreciation of narrative, and the two are interrelated.

Keywords: empathy, narratives, person-centred, perspective, perspective-taking

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Authors: LouAnne Boyd

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From the perspective of self-advocates, the biggest unaddressed problem is not the symptoms of an autism spectrum diagnosis but the social stigma that accompanies autism. This societal perspective is in contrast to the focus on the majority of interventions. Autism interventions, and consequently, most innovative technologies for autism, aim to improve deficits that occur within the person. For example, the most common Human-Computer Interaction research projects in assistive technology for autism target social skills from a normative perspective. The premise of the autism technologies is that difficulties occur inside the body, hence, the medical model focuses on ways to improve the ailment within the person. However, other technological approaches to support people with autism do exist. In the realm of Human Computer Interaction, there are other modes of research that provide critique of the medical model. For example, critical design, whose intended audience is industry or other HCI researchers, provides products that are the opposite of interventionist work to bring attention to the misalignment between the lived experience and the societal perception of autism. For example, parodies of interventionist work exist to provoke change, such as a recent project called Facesavr, a face covering that helps allistic adults be more independent in their emotional processing. Additionally, from a critical disability studies’ perspective, assistive technologies perpetuate harmful normalizing behaviors. However, these critical approaches can feel far from the frontline in terms of taking direct action to positively impact end users. From a critical yet more pragmatic perspective, projects such as Counterventions lists ways to reduce the likelihood of perpetuating ableism in interventionist’s work by reflectively analyzing a series of evolving assistive technology projects through a societal lens, thus leveraging the momentum of the evolving ecology of technologies for autism. Therefore, all current paradigms fall short of addressing the largest need—the negative impact of social stigma. The current work introduces a new paradigm for technologies for autism, borrowing from a paradigm introduced two decades ago around changing the narrative related to eating disorders. It is the shift from reprimanding poor habits to celebrating positive aspects of eating. This work repurposes Celebratory Technology for Neurodiversity and intended to reduce social stigma by targeting for the public at large. This presentation will review how requirements were derived from current research on autism social stigma as well as design sessions with autistic adults. Congruence between these two sources revealed three key design implications for technology: provide awareness of the autistic experience; generate acceptance of the neurodivergence; cultivate an appreciation for talents and accomplishments of neurodivergent people. The current pilot work in Celebratory Technology offers a new paradigm for supporting autism by shifting the burden of change from the person with autism to address changing society’s biases at large. Shifting the focus of research outside of the autistic body creates a new space for a design that extends beyond the bodies of a few and calls on all to embrace humanity as a whole.

Keywords: neurodiversity, social stigma, accessibility, inclusion, celebratory technology

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Authors: Aleksandra Bylinska, Samantha Slight-Webb, Kevin Thomas, Miles Smith, Susan Macwana, Nicolas Dominguez, Eliza Chakravarty, Joan T. Merrill, Judith A. James, Joel M. Guthridge

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Background: Systemic Lupus Erythematosus (SLE) is an interferon-related autoimmune disease characterized by B cell dysfunction. One of the main hallmarks is a loss of tolerance to self-antigens leading to increased levels of autoantibodies against nuclear components (ANAs). However, up to 20% of healthy ANA+ individuals will not develop clinical illness. SLE is more prevalent among women and minority populations (African, Asian American and Hispanics). Moreover, African Americans have a stronger interferon (IFN) signature and develop more severe symptoms. The exact mechanisms involved in ethnicity-dependent B cell dysregulation and the progression of autoimmune disease from ANA+ healthy individuals to clinical disease remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from African (AA) and European American (EA) ANA- (n=12), ANA+ (n=12) and SLE (n=12) individuals were assessed by multimodal scRNA-Seq/CITE-Seq methods to examine differential gene signatures in specific B cell subsets. Library preparation was done with a 10X Genomics Chromium according to established protocols and sequenced on Illumina NextSeq. The data were further analyzed for distinct cluster identification and differential gene signatures in the Seurat package in R and pathways analysis was performed using Ingenuity Pathways Analysis (IPA). Results: Comparing all subjects, 14 distinct B cell clusters were identified using a community detection algorithm and visualized with Uniform Manifold Approximation Projection (UMAP). The proportion of each of those clusters varied by disease status and ethnicity. Transitional B cells trended higher in ANA+ healthy individuals, especially in AA. Ribonucleoprotein high population (HNRNPH1 elevated, heterogeneous nuclear ribonucleoprotein, RNP-Hi) of proliferating Naïve B cells were more prevalent in SLE patients, specifically in EA. Interferon-induced protein high population (IFIT-Hi) of Naive B cells are increased in EA ANA- individuals. The proportion of memory B cells and plasma cells clusters tend to be expanded in SLE patients. As anticipated, we observed a higher signature of cytokine-related pathways, especially interferon, in SLE individuals. Pathway analysis among AA individuals revealed an NRF2-mediated Oxidative Stress response signature in the transitional B cell cluster, not seen in EA individuals. TNFR1/2 and Sirtuin Signaling pathway genes were higher in AA IFIT-Hi Naive B cells, whereas they were not detected in EA individuals. Interferon signaling was observed in B cells in both ethnicities. Oxidative phosphorylation was found in age-related B cells (ABCs) for both ethnicities, whereas Death Receptor Signaling was found only in EA patients in these cells. Interferon-related transcription factors were elevated in ABCs and IFIT-Hi Naive B cells in SLE subjects of both ethnicities. Conclusions: ANA+ healthy individuals have altered gene expression pathways in B cells that might drive apoptosis and subsequent clinical autoimmune pathogenesis. Increases in certain regulatory pathways may delay progression to SLE. Further, AA individuals have more elevated activation pathways that may make them more susceptible to SLE.

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Procedia PDF Downloads 149

Authors: Maria Zulema Morquecho Vega, Fabiola CarolinaMiranda Castro, Rafael Verdugo Miranda, Ignacio Yocupicio Villegas, Ana lidia Barron Raygoza, Martin enrique MArquez Cordova, Jose Alberto Duarte Moller

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Background: Anemopsis californica, also called (tame grass) belongs to the Saururaceae family small, green plant. The blade is long and wide. Gives a white flower. The plant population is only found in humid, swampy habitats, it grows where there is water, along the banks of streams and water holes. In the winter, it dries up. The leaves, rhizomes, or roots of this plant have been used to treat a range of diseases. Some of its healing properties are used to treat wounds, cold and flu symptoms, spasmodic cough, infection, pain and inflammation, burns, swollen feet, as well as lung ailments, asthma, circulatory problems (varicose veins), rheumatoid arthritis, purifies blood, helps in urinary and digestive tract diseases, sores and healing, for headache, sore throat, diarrhea, kidney pain. The tea made from the leaves and roots is used to treat uterine cancer, womb cancer, relieves menstrual pain and stops excessive bleeding after childbirth. It is also used as a gynecological treatment for infections, hemorrhoids, candidiasis and vaginitis. Objective: To study the cytotoxicity of gels prepared with silver nanoparticles in AC extract combined with chitosan, collagen and hyaluronic acid as an alternative therapy for skin conditions. Methods: The Ag NPs were synthesized according to the following method. A 0.3 mg/mL solution is prepared in 10 ml of deionized water, adjust to pH 12 with NaOH, stirring is maintained constant magnetic and a temperature of 80 °C. Subsequently, 100 ul of a 0.1 M AgNO3 solution and kept stirring constantly for 15 min. Once the reaction is complete, measurements are performed by UV-Vis. A gel was prepared in a 5% solution of acetic acid with the respective nanoparticles and AC extract of silver in the extract of AC. Chitosan is added until the process begins to occur gel. At that time, collagen will be added in a ratio of 3 to 5 drops, and later, hyaluronic acid in 2% of the total compound formed. Finally, after resting for 24 hours, the cytotoxic effect of the gels was studied. in the presence of highly positive bacteria Staphylococcus aureus and highly negative for Escherichia coli. Cultures will be incubated for 24 hours in the presence of the compound and compared with the reference. Results: Silver nanoparticles obtained had a spherical shape and sizes among 20 and 30 nm. UV-Vis spectra confirm the presence of silver nanoparticles showing a surface plasmon around 420 nm. Finally, the test in presence of bacteria yield a good antibacterial property of this nanocompound and tests in people were successful. Conclusion: Gel prepared by biogenic synthesis shown beneficious effects in severe acne, acne vulgaris and wound healing with diabetic patients.

Keywords: anemopsis californica, nanomedicina, biotechnology, biomedicine

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Authors: Majed Al Otaibi, Melissa Lessard-Beaudoin, Amel Loudghi, Raphael Chouinard-Watkins, Melanie Plourde, Frederic Calon, C. Alexandre Castellano, Stephen Cunnane, Helene Payette, Pierrette Gaudreau, Denis Gris, Rona K. Graham

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Introduction: Alzheimer disease (AD) is a chronic disorder that affects millions of individuals worldwide. Symptoms include memory dysfunction, and also alterations in attention, planning, language and overall cognitive function. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Studying the mechanisms underlying the olfactory dysfunction may therefore lead to the discovery of potential biomarkers and/or treatments for neurodegenerative diseases. Objectives: To determine if olfactory dysfunction predicts future cognitive impairment in the aging population and to characterize the olfactory system in a murine model expressing a genetic factor of AD. Method: For the human study, quantitative olfactory tests (UPSIT and OMT) have been done on 93 subjects (aged 80 to 94 years) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge) cohort accepting to participate in the ORCA secondary study. The telephone Modified Mini Mental State examination (t-MMSE) was used to assess cognition levels, and an olfactory self-report was also collected. In a separate cohort, olfactory cortical volume was calculated using MRI results from healthy old adults (n=25) and patients with AD (n=18) using the AAL single-subject atlas and performed with the PNEURO tool (PMOD 3.7). For the murine study, we are using Western blotting, RT-PCR and immunohistochemistry. Result: Human Study: Based on the self-report, 81% of the participants claimed to not suffer from any problem with olfaction. However, based on the UPSIT, 94% of those subjects showed a poor olfactory performance and different forms of microsmia. Moreover, the results confirm that olfactory function declines with age. We also detected a significant decrease in olfactory cortical volume in AD individuals compared to controls. Murine study: Preliminary data demonstrate there is a significant decrease in expression levels of the proform of caspase-3 and the caspase substrate STK3, in the olfactory bulb of mice expressing human APOE4 compared with controls. In addition, there is a significant decrease in the expression level of the caspase-9 proform and caspase-8 active fragment. Analysis of the mature neuron marker, NeuN, shows decreased expression levels of both isoforms. The data also suggest that Iba-1 immunostaining is increased in the olfactory bulb of APOE4 mice compared to wild type mice. Conclusions: The activation of caspase-3 may be the cause of the decreased levels of STK3 through caspase cleavage and may play role in the inflammation observed. In the clinical study, our results suggest that seniors are unaware of their olfactory function status and therefore it is not sufficient to measure olfaction using the self-report in the elderly. Studying olfactory function and cognitive performance in the aging population will help to discover biomarkers in the early stage of the AD.

Keywords: Alzheimer's disease, APOE4, cognition, caspase, brain atrophy, neurodegenerative, olfactory dysfunction

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Authors: Jiri Nepereny, Vladimir Vrzal

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Staphylococcus intermedius/pseudintermedius bacteria are commonly found on the skin of healthy dogs and can cause pruritic skin diseases under certain circumstances (trauma, allergy, immunodeficiency, ectoparasitosis, endocrinological diseases, glucocorticoid therapy, etc.). These can develop into complicated superficial or deep pyoderma, which represent a large group of problematic skin diseases in dogs. These are predominantly inflammations of a secondary nature, associated with the occurrence of coagulase-positive Staphylococcus spp. A major problem is increased itching, which greatly complicates the healing process. The aim of this work is to verify the efficacy of the developed preparation Bacteriophage SI (Staphylococcus intermedius). The tested preparation contains a lysate of bacterial cells of S. intermedius host culture including culture medium and live virions of specific phage. Sodium Merthiolate is added as a preservative in a safe concentration. Validation of the efficacy of the product was demonstrated by monitoring the therapeutic effect after application to indicated cases from clinical practice. The indication for inclusion of the patient into the trial was an adequate history and clinical examination accompanied by sample collection for bacteriological examination and isolation of the specific causative agent. Isolate identification was performed by API BioMérieux identification system (API ID 32 STAPH) and rep-PCR typing. The suitability of therapy for a specific case was confirmed by in vitro testing of the lytic ability of the bacteriophage to lyse the specific isolate = formation of specific plaques on the culture isolate on the surface of the solid culture medium. So far, a total of 32 dogs of different sexes, ages and breed affiliations with different symptoms of staphylococcal dermatitis have been included in the testing. Their previous therapy consisted of more or less successful systemic or local application of broad-spectrum antibiotics. The presence of S. intermedius/pseudintermedius has been demonstrated in 26 cases. The isolates were identified as a S. pseudintermedius, in all cases. Contaminant bacterial microflora was always present in the examined samples. The test product was applied subcutaneously in gradually increasing doses over a period of 1 month. After improvement in health status, maintenance therapy was followed by application of the product once a week for 3 months. Adverse effects associated with the administration of the product (swelling at the site of application) occurred in only 2 cases. In all cases, there was a significant reduction in clinical signs (healing of skin lesions and reduction of inflammation) after therapy and an improvement in the well-being of the treated animals. A major problem in the treatment of pyoderma is the frequent resistance of the causative agents to antibiotics, especially the increasing frequency of multidrug-resistant and methicillin-resistant S. pseudintermedius (MRSP) strains. Specific phagolysate using for the therapy of these diseases could solve this problem and to some extent replace or reduce the use of antibiotics, whose frequent and widespread application often leads to the emergence of resistance. The advantage of the therapeutic use of bacteriophages is their bactericidal effect, high specificity and safety. This work was supported by Project FV40213 from Ministry of Industry and Trade, Czech Republic.

Keywords: bacteriophage, pyoderma, staphylococcus spp, therapy

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Authors: Briohny H. Spencer, Russ Chess-Williams, Catherine McDermott, Shailendra Anoopkumar-Dukie, David Christie

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Background: Prostate cancer is the second most common cancer diagnosed in men worldwide and the most prevalent in Australian men. In 2015, it was estimated that approximately 18,000 new cases of prostate cancer were diagnosed in Australia. Currently, for localised disease, androgen depravation therapy (ADT) and radiotherapy are a major part of the curative management of prostate cancer. ADT acts to reduce the levels of circulating androgens, primarily testosterone and the locally produced androgen, dihydrotestosterone (DHT), or by preventing the subsequent activation of the androgen receptor. Thus, the growth of the cancerous cells can be reduced or ceased. Radiation techniques such as brachytherapy (radiation delivered directly to the prostate by transperineal implant) or external beam radiation therapy (exposure to a sufficient dose of radiation aimed at eradicating malignant cells) are also common techniques used in the treatment of this condition. Radiotherapy (RT) has significant limitations, including reduced effectiveness in treating malignant cells present in hypoxic microenvironments leading to radio-resistance and poor clinical outcomes and also the significant side effects for the patients. Alpha1-adrenoceptor antagonists are used for many prostate cancer patients to control lower urinary tract symptoms, due to the progression of the disease itself or may arise as an adverse effect of the radiotherapy treatment. In Australia, a significant number (not a majority) of patients receive a α1-ADR antagonist and four drugs are available including prazosin, terazosin, alfuzosin and tamsulosin. There is currently limited published data on the effects of α1-ADR antagonists during radiotherapy, but it suggests these medications may improve patient outcomes by enhancing the effect of radiotherapy. Aim: To determine the impact of α1-ADR antagonists treatments on time to biochemical relapse following radiotherapy. Methods: A retrospective study of male patients receiving radiotherapy for biopsy-proven localised prostate cancer was undertaken to compare cancer outcomes for drug-naïve patients and those receiving α1-ADR antagonist treatments. Ethical approval for the collection of data at Genesis CancerCare QLD was obtained and biochemical relapse (defined by a PSA rise of >2ng/mL above the nadir) was recorded in months. Rates of biochemical relapse, prostate specific antigen doubling time (PSADT) and Kaplan-Meier survival curves were also compared. Treatment groups were those receiving α1-ADR antagonists treatment before or concurrent with their radiotherapy. Data was statistically analysed using One-way ANOVA and results expressed as mean ± standard deviation. Major findings: The mean time to biochemical relapse for tamsulosin, prazosin, alfuzosin and controls were 45.3±17.4 (n=36), 41.5±19.6 (n=11), 29.3±6.02 (n=6) and 36.5±17.6 (n=16) months respectively. Tamsulosin, prazosin but not alfuzosin delayed time to biochemical relapse although the differences were not statistically significant. Conclusion: Preliminary data for the prior and/or concurrent use of tamsulosin and prazosin showed a positive trend in delaying time to biochemical relapse although no statistical significance was shown. Larger clinical studies are indicated and with thousands of patient records yet to be analysed, it may determine if there is a significant effect of these drugs on control of prostate cancer.

Keywords: alpha1-adrenoceptor antagonists, biochemical relapse, prostate cancer, radiotherapy

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Authors: Vidhya Venugopal, Jeremiah Chinnadurai, Rebekah A. I. Lucas, Tord Kjellstrom, Bruno Lemke

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Introduction: The effects of climate change (CC) are largely discussed across the globe in terms of impacts on the environment and the general population, but the impacts on workers remain largely unexplored. The predicted rise in temperatures and heat events in the CC scenario have health implications on millions of workers in physically exerting jobs. The current health and productivity risks associated with heat exposures are characterized, future risk estimates as temperature rises and recommendations towards developing protective and preventive occupational health and safety guidelines for India are discussed. Methodology: Cross-sectional studies were conducted in several occupational sectors with workers engaged in moderate to heavy labor (n=1580). Quantitative data on heat exposures (WBGT°C), physiological heat strain indicators viz., Core temperature (CBT), Urine specific gravity (USG), Sweat rate (SwR) and qualitative data on heat-related health symptoms and productivity losses were collected. Data were analyzed for associations between heat exposures, health and productivity outcomes related to heat stress. Findings: Heat conditions exceeded the Threshold Limit Value (TLV) for safe manual work in 66% of the workers across several sectors (Avg.WBGT of 28.7°C±3.1°C). Widespread concerns about heat-related health outcomes (86%) were prevalent among workers exposed to high TLVs, with excessive sweating, fatigue and tiredness being commonly reported by workers. The heat stress indicators, core temperature (14%), Sweat rate (8%) and USG (9%), were above normal levels in the study population. A significant association was found between rise in Core Temperatures and WBGT exposures (p=0.000179) Elevated USG and SwR in the worker population indicate moderate dehydration, with potential risks of developing heat-related illnesses. In a steel industry with high heat exposures, an alarming 9% prevalence of kidney/urogenital anomalies was observed in a young workforce. Heat exposures above TLVs were associated with significantly increased odds of various adverse health outcomes (OR=2.43, 95% CI 1.88 to 3.13, p-value = <0.0001) and productivity losses (OR=1.79, 95% CI 1.32 to 2.4, p-value = 0.0002). Rough estimates for the number of workers who would be subjected to higher than TLV levels in the various RCP scenarios are RCP2.6 =79%, RCP4.5 & RCP6 = 81% and at RCP 8.5 = 85%. Rising temperatures due to CC has the capacity to further reduce already compromised health and productivity by subjecting the workers to increased heat exposures in the RCP scenarios are of concern for the country’s occupational health and economy. Conclusion: The findings of this study clearly identify that health protection from hot weather will become increasingly necessary in the Indian subcontinent and understanding the various adaptation techniques needs urgent attention. Further research with a multi-targeted approach to develop strategies for implementing interventions to protect the millions of workers is imperative. Approaches to include health aspects of climate change within sectoral and climate change specific policies should be encouraged, via a number of mechanisms, such as the “Health in All Policies” approach to avert adverse health and productivity consequences as climate change proceeds.

Keywords: heat stress, occupational health, productivity loss, heat strain, adverse health outcomes

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Authors: M. Skibinska, A. Rajewska-Rager, M. Dmitrzak-Weglarz, N. Lepczynska, P. Sibilski, P. Kapelski, J. Pawlak, J. Twarowska-Hauser

Abstract:

Introduction: Neurotrophic factors have been implicated in neuropsychiatric disorders. Brain-Derived Neurotrophic Factor (BDNF) influences neuron differentiation in development as well as synaptic plasticity and neuron survival in adulthood. BDNF is widely studied in mood disorders and has been proposed as a biomarker for depression. BDNF is synthesized as precursor protein – proBDNF. Both forms are biologically active and exert opposite effects on neurons. Aim: The aim of the study was to examine the serum levels of BDNF and proBDNF in unipolar and bipolar young patients below 24 years old during hypo/manic, depressive episodes and in remission compared to healthy control group. Methods: In a prospective 2 years follow-up study, we investigated alterations in levels of BDNF and proBDNF in 79 patients (23 males, mean age 19.08, SD 3.3 and 56 females, mean age 18.39, SD 3.28) diagnosed with mood disorders: unipolar and bipolar disorder compared with 35 healthy control subjects (7 males, mean age 20.43, SD 4.23 and 28 females, mean age 21.25, SD 2.11). Clinical characteristics including mood, comorbidity, family history, and treatment, were evaluated during control visits and clinical symptoms were rated using the Hamilton Depression Rating Scale and Young Mania Rating Scale. Serum BDNF and proBDNF concentrations were determined by Enzyme-Linked Immunosorbent Assays (ELISA) method. Serum BDNF and proBDNF levels were analysed with covariates: sex, age, age > 18 and < 18 years old, family history of affective disorders, drug-free vs. medicated status. Normality of the data was tested using Shapiro-Wilk test. Levene’s test was used to calculate homogeneity of variance. Non-parametric Tests: Mann-Whitney U test, Kruskal-Wallis ANOVA, Friedman’s ANOVA, Wilcoxon signed rank test, Spearman correlation coefficient were applied in analyses The statistical significance level was set at p < 0.05. Results: BDNF and proBDNF serum levels did not differ between patients at baseline and controls as well as comparing patients in acute episode of depression/hypo/mania at baseline and euthymia (at month 3 or 6). Comparing BDNF and proBDNF levels between patients in euthymia and control group no differences have been found. Increased BDNF level in women compared to men at baseline (p=0.01) have been observed. BDNF level at baseline was negatively correlated with depression and mania occurence at 24 month (p=0.04). BDNF level at 12 month was negatively correlated with depression and mania occurence at 12 month (p=0.01). Correlation of BDNF level with sex have been detected (p=0.01). proBDNF levels at month 3, 6 and 12 negatively correlated with disease status (p=0.02, p=0.008, p=0.009, respectively). No other correlations of BDNF and proBDNF levels with clinical and demographical variables have been detected. Discussion: Our results did not show any differences in BDNF and proBDNF levels between depression, mania, euthymia, and controls. Imbalance in BDNF/proBDNF signalling may be involved in pathogenesis of mood disorders. Further studies on larger groups are recommended. Grant was founded by National Science Center in Poland no 2011/03/D/NZ5/06146.

Keywords: bipolar disorder, Brain-Derived Neurotrophic Factor (BDNF), proBDNF, unipolar depression

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Authors: Nervana Elbakary, Sami Ouanes, Sadaf Riaz, Oraib Abdallah, Islam Mahran, Noriya Al-Khuzaei, Yassin Eltorki

Abstract:

Major Depressive Disorder (MDD) requires therapeutic interventions during the initial month after being diagnosed for better disease outcomes. International guidelines recommend a duration of 4–12 weeks for an initial antidepressant (IAD) trial at an optimized dose to get a response. If depressive symptoms persist after this duration, guidelines recommend switching, augmenting, or combining strategies as the next step. Most patients with MDD in the mental health setting have been labeled incorrectly as treatment-resistant where in fact they have not been subjected to an adequate trial of guideline-recommended therapy. Premature discontinuation of IAD due to ineffectiveness can cause unfavorable consequences. Avoiding irrational practices such as subtherapeutic doses of IAD, premature switching between the ADs, and refraining from unjustified polypharmacy can help the disease to go into a remission phase We aimed to determine the prevalence and the patterns of strategies applied after an IAD was changed because of a suboptimal response as a primary outcome. Secondary outcomes included the median survival time on IAD before any change; and the predictors that were associated with IAD change. This was a retrospective cross- sectional study conducted in Mental Health Services in Qatar. A dataset between January 1, 2018, and December 31, 2019, was extracted from the electronic health records. Inclusion and exclusion criteria were defined and applied. The sample size was calculated to be at least 379 patients. Descriptive statistics were reported as frequencies and percentages, in addition, to mean and standard deviation. The median time of IAD to any change strategy was calculated using survival analysis. Associated predictors were examined using two unadjusted and adjusted cox regression models. A total of 487 patients met the inclusion criteria of the study. The average age for participants was 39.1 ± 12.3 years. Patients with first experience MDD episode 255 (52%) constituted a major part of our sample comparing to the relapse group 206(42%). About 431 (88%) of the patients had an occurrence of IAD change to any strategy before end of the study. Almost half of the sample (212 (49%); 95% CI [44–53%]) had their IAD changed less than or equal to 30 days. Switching was consistently more common than combination or augmentation at any timepoint. The median time to IAD change was 43 days with 95% CI [33.2–52.7]. Five independent variables (age, bothersome side effects, un-optimization of the dose before any change, comorbid anxiety, first onset episode) were significantly associated with the likelihood of IAD change in the unadjusted analysis. The factors statistically associated with higher hazard of IAD change in the adjusted analysis were: younger age, un-optimization of the IAD dose before any change, and comorbid anxiety. Because almost half of the patients in this study changed their IAD as early as within the first month, efforts to avoid treatment failure are needed to ensure patient-treatment targets are met. The findings of this study can have direct clinical guidance for health care professionals since an optimized, evidence-based use of AD medication can improve the clinical outcomes of patients with MDD; and also, to identify high-risk factors that could worsen the survival time on IAD such as young age and comorbid anxiety

Keywords: initial antidepressant, dose optimization, major depressive disorder, comorbid anxiety, combination, augmentation, switching, premature discontinuation

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Authors: Prem Kumar, Anuj Tyagi, Harsh Panwar, Vaneet Inder Kaur

Abstract:

Though aquaculture started as an occupation for poor and weak farmers for livelihood, it has now acquired the shape of one of the biggest industry to grow live protein in the form of aquatic organisms. Industrialization of the aquaculture sector has led to intensification resulting in stress on aquatic organisms and frequent disease outbreaks leading to huge economic impacts. Indiscriminate use of antibiotics as growth promoter and prophylactic agent in aquaculture has resulted in rapid emergence and spread of antibiotic resistance in bacterial pathogens. Over the past few years, use of probiotics (as an alternative of antibiotics) in aquaculture has gained attention due to their immunostimulant and growth promoting properties. It has now well known that after administration, a probiotic bacterium has to compete and establish itself against native microbiota to show its eventual beneficial properties. Due to their non-fish origin, commercial probiotics sometimes may display poor probiotic functionalities and antagonistic effects. Thus, isolation and characterization of probiotic bacteria from same fish host is very much necessary. In this study, attempts were made to isolate potent probiotic lactic acid bacteria (LAB) from intestinal microflora of rohu fish. Twenty-five experimental rohu fishes (mean weight 400 ± 20gm, mean standard length 20 ± 3cm) were used in the study to collect fish gut after dissection in a sterile condition. A total of 150 tentative LAB isolates from selective agar media (de Man-Rogosa-Sharpe (MRS)) were screened for their antimicrobial activity against Aeromonas hydrophila and Microccocus leuteus. A total of 17 isolates, identified as Lactobacillus plantarum and Lactococcus lactis, identified by biochemical tests and PCR amplification and sequencing of 16S rRNA gene fragment, displayed promising antimicrobial activity against both the pathogens. Two isolates from each species (FLB1, FLB2 from L. plantarum; and FLC1, FLC2 from L. lactis) were subjected to downstream probiotic potential characterization. These isolates were compared in vitro for their hemolytic activity, acid and bile tolerance for growth kinetics, auto-aggregation, cell-surface hydrophobicity against xylene, and chloroform, tolerance to phenol, cell adhesion, and safety parameters (by intraperitoneal and intramuscular injections). None of the tested isolates showed any hemolytic activity indicating their potential safety. Moreover, these isolates were tolerant to 0.3% bile (75-82% survival), phenol stress (96-99% survival) with 100% viability at pH 3 over a period of 3 h. Antibiotic sensitivity test revealed that all the tested LAB isolates were resistant to vancomycin, gentamicin, streptomycin, and erythromycin and sensitive to Erythromycin, Chloramphenicol, Ampicillin, Trimethoprim, and Nitrofurantoin. Tetracycline resistance was found in L. plantarum (FLB1 and FLB2 isolates), whereas L. lactis were susceptible to it. Intramuscular and intraperitoneal challenges to fingerlings of rohu fish (5 ± 1gm weight) with FLB1 showed no pathogenicity and occurrence of disease symptoms in fishes over an observation period of 7 days. The results revealed FLB1 as a potential probiotic candidate for aquaculture application among other isolates.

Keywords: aquaculture, Lactobacillus plantarum, Lactococcus lactis, probiotics

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Authors: Rocio Murad, Marcela Sanchez, Mariana Calderon Jaramillo, Danny Rivera, Angela Cifuentes, Daniela Roldán, Juan Carlos Rivillas

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Women and girls have specific health needs, but during health pandemics such as COVID19 they are less likely to have access to quality essential health information, commodities and services, or insurance coverage for routine and catastrophic health expenses, especially in rural and marginalized communities. This is compounded by multiple or intersecting inequalities, such as ethnicity, socioeconomic status, disability, age, geographic location, and sexual orientation, among others. Despite concerted collective action, there is a lack of information on the situation of women, adolescents and youth, including gender inequalities exacerbated by the pandemic. Much more needs to be done to amplify the lived realities of women and adolescents in global and national advocacy and policy responses. The COVID 19 pandemic reflects the need for systematic advocacy policies based on the lived experiences of women and adolescents, underpinned by human rights. This research is part of the initiative of Profamilia Association (Solidarity Study), and its objective is twofold: i) to analyze the behavioral changes and immediate expectations of Colombians during the stage of relaxation of the confinement measures decreed by the national government; and ii) to identify the needs, experiences and resilient practices of adolescents and young women during the COVID-19 crisis in Colombia. Descriptive analysis of data collected by Profamilia through the Solidaridad study, an exploratory cross-sectional descriptive study that used subnational level data from a nonprobabilistic sample survey conducted to 1735 adults, between September 01 and 11, 2020. Interviews were conducted with key stakeholders about their experiences during COVID19, under three key axes: i) main challenges for adolescents and young women; ii) examples of what has worked well in responding to the challenge; and iii) how/what services are/should be provided during COVID-19 (and beyond) to address the challenge. Interviewees were selected based on prior mapping of social groups of interest. In total, 23 adolescents and young women participated in the interviews. The results show that people adopted behavioral changes such as wearing masks, avoiding people with symptoms, and reducing mobility, but there was also a doubling of concerns for many reasons, from effects on mental health, sexual health, and unattended reproductive health to the burden of care and working at home. The favorable perception that people had at the beginning of the quarantine about the response and actions of the national and local government to control Covid-19 decreased over the course of the quarantine. The challenges and needs of adolescents and young women were highlighted during the most restrictive measures to contain the COVID-19 pandemic, which resulted in disruptions to daily activities, education and work, as well as restrictions to mobility and social interaction. Concerns raised by participants included: impact on mental health and wellbeing due to disruption of daily life; limitations in access to formal and informal education; food insecurity; migration; loss of livelihoods; lack of access to health information and services; limitations to sexual and reproductive health and rights; insecurity problems; and problems in communication and treatment among household members.

Keywords: COVID-19, changes in behavior, adolescents, women

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Authors: Abdulaziz Alakeel, Abdulrahman Alomair, Mohammed Fouda

Abstract:

Introduction: Methotrexate (MTX) is an antimetabolite used to treat multiple conditions, including neoplastic diseases, severe psoriasis, and rheumatoid arthritis. Skin cancer is the out-of-control growth of abnormal cells in the epidermis, the outermost skin layer, caused by unrepaired DNA damage that triggers mutations. These mutations lead the skin cells to multiply rapidly and form malignant tumors. The aim of this review is to evaluate the risk of skin cancer associated with the use of methotrexate and to suggest regulatory recommendations if required. Methodology: Signal Detection team at Saudi Food and Drug Authority (SFDA) performed a safety review using National Pharmacovigilance Center (NPC) database as well as the World Health Organization (WHO) VigiBase, alongside with literature screening to retrieve related information for assessing the causality between skin cancer and methotrexate. The search conducted in July 2020. Results: Four published articles support the association seen while searching in literature, a recent randomized control trial published in 2020 revealed a statistically significant increase in skin cancer among MTX users. Another study mentioned methotrexate increases the risk of non-melanoma skin cancer when used in combination with immunosuppressant and biologic agents. In addition, the incidence of melanoma for methotrexate users was 3-fold more than the general population in a cohort study of rheumatoid arthritis patients. The last article estimated the risk of cutaneous malignant melanoma (CMM) in a cohort study shows a statistically significant risk increase for CMM was observed in MTX exposed patients. The WHO database (VigiBase) searched for individual case safety reports (ICSRs) reported for “Skin Cancer” and 'Methotrexate' use, which yielded 121 ICSRs. The initial review revealed that 106 cases are insufficiently documented for proper medical assessment. However, the remaining fifteen cases have extensively evaluated by applying the WHO criteria of causality assessment. As a result, 30 percent of the cases showed that MTX could possibly cause skin cancer; five cases provide unlikely association and five un-assessable cases due to lack of information. The Saudi NPC database searched to retrieve any reported cases for the combined terms methotrexate/skin cancer; however, no local cases reported up to date. The data mining of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by the WHO Uppsala Monitoring Centre to measure the reporting ratio. Positive IC reflects higher statistical association, while negative values translated as a less statistical association, considering the null value equal to zero. Results showed that a combination of 'Methotrexate' and 'Skin cancer' observed more than expected when compared to other medications in the WHO database (IC value is 1.2). Conclusion: The weighted cumulative pieces of evidence identified from global cases, data mining, and published literature are sufficient to support a causal association between the risk of skin cancer and methotrexate. Therefore, health care professionals should be aware of this possible risk and may consider monitoring any signs or symptoms of skin cancer in patients treated with methotrexate.

Keywords: methotrexate, skin cancer, signal detection, pharmacovigilance

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Authors: Vijay Samuel, Tina Thekkekkara, Shoma Ganguly

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There is no reported Hanta Seoul virus infection in children in the UK so far, making it quite challenging for clinicians in diagnosing, predicting and prognosticating the outcome of the infection to patients and parents. We report a case of a ten-year-old girl who presented with pyrexia associated with headache, photophobia and abdominal pain. The family had recently acquired two pet rats six weeks ago. She appeared flushed with peri-oral pallor, coated the strawberry tongue, inflamed tonsils and bilateral cervical lymphadenopathy. Her liver and splenic edges were palpable. Investigations showed that she was thrombocytopenic with deranged renal and liver functions. An ultrasound abdomen demonstrated a mildly enlarged spleen, peripancreatic lymph node and an acalculous cholecystitis. In view of her clinical presentation, a diagnosis of leptospirosis was considered and she was commenced on intravenous benzylpenicillin. The following day she became oliguric, developed significant proteinuria and her renal function deteriorated. Following conservative management, her urine output gradually improved along with her renal function, proteinuria and thrombocytopaenia. Serology for leptospirosis and various other viruses were negative. Following discussion with the Rare and Imported Pathogens Laboratory at Porton hanta virus serology was requested and found to be strongly positive for Seoul hanta virus. Following discharge she developed palpitations, fatigue, severe headache and cognitive difficulties including memory loss and difficulties in spelling, reading and mathematics. Extensive investigations including ECG, MRI brain and CSF studies were performed and revealed no significant abnormalities. Since 2012, there have been six cases of acute kidney injury due to Hantavirus infection in the UK. Two cases were from the Humber region and were exposure to wild rats and the other four were exposed to specially bred pet fancy rats. Hanta virus infections can cause mild flu like symptoms but two clinical syndromes are associated with severe disease including haemorrhagic fever with renal syndrome, which may be associated with thrombocytopenia and Hantavirus cardiopulmonary syndrome. Neuropsychological impairments reported following hantavirus pulmonary syndrome and following Puumala virus infection have been reported. Minor white matter lesions were found in about half of the patients investigated with MRI brain. Seoul virus has a global distribution owing to the dispersal of its carrier host rats, through global trade. Several ports in the region could explain the possible establishment of Seoul virus in local populations of rats in the Yorkshire and Humber region. The risk of infection for occupationally exposed groups is 1-3% compared to 32.9% for specialist pet rat owners. The report highlight’s the importance of routinely asking about pets in the family. We hope to raise awareness of the emergence of hantavirus infection in the UK, particularly in the Yorkshire and Humber region. Clinicians should consider hantavirus infection as a potential cause of febrile illness causing renal impairment in children. Awareness of the possible neuro-cognitive sequele would help the clinicians offer appropriate information and support to children and their families. Contacting Rare and Imported Pathogens Laboratory at Porton is a useful resource for clinicians in UK when they consider unusual infections.

Keywords: Seoul hantavirus in child Porton, UK Acute kidney injury

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Authors: Jelena Maletkovic

Abstract:

Background: Endogenous Cushing’s syndrome is a rare disease, but iatrogenic or drug related Cushing syndrome from glucocorticoid products is commonly seen in clinical practice. With high dose and long term use of glucocorticoids, patients can develop isolated hypothalamic-pituitary-adrenal (HPA) suppression, or HPA axis suppression can be accompanied by overt iatrogenic Cushing’s syndrome. This is a rare case where severe Cushing’s syndrome developed from an unknown medication and was followed by severe and prolonged adrenal insufficiency and multiple potentially fatal complications. Case: This is a 37-year-old woman who is presented to Emergency Room (ER) with shortness of breath and chest pain. Four months prior to this presentation the patient was a generally healthy woman who was looking for improvement in her appearance and visited local Rejuvenation Clinic. After initial consultation with a nurse, she was contacted by a physician over the phone and was advised to start taking multiple injectable medications that will arrive by mail. Medications without any labels on bottles were delivered and the patient started daily intramuscular injections. Over the next two months, she noticed rounding of her face and swelling around her eyes. She gained 20 pounds, mostly abdominal fat and became extremely fatigued. Her muscles on legs were visibly decreasing in size and she felt significant muscle weakness. Unexplained bruising occurred. She started growing hair on face and developed secondary amenorrhea. New severe back pain started. She developed depression and headaches. Finally, over a few days, a number of red-purple stretch marks that were sensitive and painful appeared over her abdomen, upper part of arms and legs. She then became suspicious that these dramatic symptoms are caused by injectable medication and she discontinued injections. Over the next few days she presented to ER with low blood pressure and oxygen saturation of 75%. Studies revealed extensive pneumonia as well as multiple pulmonary emboli. Her white blood count was elevated with 32 000 and she also had acute kidney failure on admission. She was treated for sepsis and was also given stress dose steroids. Steroids were tapered over 48 hours and discontinued. After being discharged to home, on her first visit to endocrinology clinic she had undetectable ACTH of < 2pg/mL and undetectable 8am cortisol of < 0.2mcg/dL. She did not respond to an intramuscular injection of cosyntropin 250mcg and her repeated cortisol after 60 minutes was only 1mcg/dL. The patient was diagnosed with adrenal insufficiency and was started on hydrocortisone 20mg+10mg. It took close to 2 years of slow tapering for recovery of this patient’s HPA axis and resolve all the sequelae from Cushing’s syndrome. Conclusion: Misuse and abuse of glucocorticoids have been present almost since these medications were discovered. This is a rare case where not only severe Cushing’s syndrome in full clinical picture developed but also the patient suffered multiple potentially fatal complications and prolonged adrenal insufficiency. Visits to herbal, rejuvenation, esthetic, and similar clinics are becoming more and more popular and physicians need to be aware of possible non-benign nature of medications that their patients may be using.

Keywords: iatrogenic, Cushing's syndrome, adrenal crisis, steroid abuse

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