Search results for: animal diagnosis of tuberculosis

Authors: Seyed Davar Siadat, Samira Tarashi, Abolfazl Fateh, Arfa Moshiri

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Background: The global health issue of tuberculosis (TB) still affects patients in every country. TB control may not be as effective as it should be, especially when resistant strains are involved. In this regard, mycobacterial MTases play a major role in tuberculosis, but the mechanisms underlying their function have yet to be fully deciphered. Methods: Five resistant isolates of M.tb were accumulated. As a reference strain, M.tb H37Rv (ATCC 27249) was used. For this analysis, seven putative mycobacterial MTase genes (Rv0645c, Rv1694, Rv2966c, Rv3919c, Rv2756c, Rv1988, and Rv3263), as well as Rv1392 as SAM synthase, were selected. Comparing mutations and expression levels of MTases in different strains was accomplished by PCR-sequencing and qRT-PCR. The relative expression levels of these genes were calculated using the 2 -ΔΔCt method. Results: The Rv3919c gene (T to G in codon 341) and Rv1392 gene (G to A in codon 97) were the only mutations found in the INHR strain. In all sensitive and resistant isolates, Rv0645c, Rv3263, Rv2756c, and Rv2966c were overexpressed. However, the expression of Rv1988 and Rv3919c decreased in the sensitive strains, whereas the expression of Rv1694 increased. There was also a decreased expression of Rv1392 in the INHR isolate. Conclusion: The presence of mycobacterial MTases as well as resistance to antibiotics were found to be correlated in M.tb strains. Undoubtedly, there are some MTases that are associated with the virulence process. It is necessary to conduct additional studies to fully explore the impact of mycobacterial MTases within specific strains of M.tb to develop novel diagnostic and treatment strategies.

Keywords: mycobacterium tuberculosis, drug resistance, methyltransferases, s-adenosylmethionine

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Authors: Yadav R. K., Baral S.

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Introduction: Nepal is one of the world’s least developed countries and has a high incidence of tuberculosis (TB). The TB prevalence survey in 2019 showed 69,000 Nepalese is developing TB and 4,000 die every year. Given its disproportionate impact on the impoverished segments of society, TB often thrusts patients into extreme poverty or exacerbates their existing economic struggles. Consequently, not only the patients but also their families suffer from the loss of livelihood. This study aims to assess the support of nutritional allowance on treatment compliance among retreatment tuberculosis patients in Nepal. This is a secondary analysis of data from HMIS (Health Management Information System) to investigate treatment compliance among tuberculosis patients and its association with nutritional allowance. The study population consisted of all individuals (N=2972) who had received services from July 16, 2021, to December 14, 2022. The SPSS 21version was used to conduct descriptive and bivariate analysis. Out of the total TB patients (n=2972), a third-fourth (65.9%) of TB patients were male. More than one-tenth (12.3%) of respondents received a nutrition support allowance. The TB treatment compliance rate was more (89.91%) in the nutrition support allowance group compared to the non-nutritional support group (87.98%). TB patients who received the nutritional support allowance were nearly twice as likely to have a higher TB treatment compliance rate compared to those who did not receive the nutritional support allowance. Providing nutritional allowance support to tuberculosis (TB) patients can play a significant role in improving treatment compliance and outcomes. Age and the type of TB are important factors that have shown statistical significance in relation to treatment compliance. Therefore, it is recommended to provide nutritional allowance support to both new and retreatment TB patients. To enhance treatment compliance among TB patients, it is beneficial to provide timely nutrition allowances and arrange home visits by TB focal persons.

Keywords: nutrition, support, treatment compliance, TB, Nepal

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Authors: Purnima Pandit

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Malaria remains one of the world’s most deadly infectious disease and arguably, the greatest menace to modern society in terms of morbidity and mortality. To choose the right treatment and to ensure a quality of life suitable for a specific patient condition, early and accurate diagnosis of malaria is essential. It reduces transmission of disease and prevents deaths. Our work focuses on designing an efficient, accurate fuzzy inference system for malaria diagnosis.

Keywords: fuzzy inference system, fuzzy logic, malaria disease, triangular fuzzy number

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Authors: Ulil Afidah, Mustopa

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The study aims to determine the assessment of animal welfare at slaughterhouses in Badung district, Bali province. The study was conducted for ten days with observed five cattle per day with a total 50 cattle. Observation begins when a cow came out of the pick up to be slaughtered, subsequently recorded in a questionnaire that has been provided.The result of the observation showed that the slaughterhouses in Bandung district have the implemented animal welfare which fulfills the requirement that is 63% before slaughtering process, and 76% at slaughtering process. Based on these results it can be concluded in slaughterhouses of Badung district already fulfill the requirements.

Keywords: animal welfare, assesment, Badung district, slaughterhousess

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Authors: Pratiksha Saxena, Dipti Singh, Neha Khanna

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A self-organizing migrating genetic algorithm(C-SOMGA) is developed for animal diet formulation. This paper presents animal diet formulation using stochastic and genetic algorithm. Tri-objective models for cost minimization and shelf life maximization are developed. These objectives are achieved by combination of stochastic programming and C-SOMGA. Stochastic programming is used to introduce nutrient variability for animal diet. Self-organizing migrating genetic algorithm provides exact and quick solution and presents an innovative approach towards successful application of soft computing technique in the area of animal diet formulation.

Keywords: animal feed ration, feed formulation, linear programming, stochastic programming, self-migrating genetic algorithm, C-SOMGA technique, shelf life maximization, cost minimization, nutrient maximization

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Authors: Atefeh Abedini, Pegah Soltani, Arda Kiani

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Background: Sarcoidosis and Tuberculosis are both considered granulomatous chronic diseases with some similar pulmonary and extra-pulmonary manifestations. It is hypothesized that given these morphological similarities, the genome of mycobacterium could have an impact on the development of Sarcoidosis. Identifying the potential correlation of these diseases may assist in the management of sarcoidosis. Herein, we aimed to inspect the lymph node biopsy of sarcoidosis patients for the existence of the HSP-65 mycobacterium DNA sequence. Methods: This cross-sectional survey was conducted on 1188 Sarcoidosis patients without active/latent tuberculosis infection who were diagnosed in Masih Daneshvari Hospital in Tehran, Iran, from January 2020 to January 2022. Trans-bronchial needle aspiration (TBNA) was performed due to bilateral hilar lymphadenopathy to take a specimen. Results: The under-evaluated patients were mainly women (N=815 (68.6%)), none-smoker (N=1016 (85.5%)), and middle-aged (50.1 (SD=4.22)) with average angiotensin-converting enzyme (ACE) index of 75.6 (SD=6.42). Dyslipidemias (n=314 (26.4%), Hypertension (n=295 (24.8%)), Diabetes mellitus (n=131 (11.0%)), and chronic heart diseases (n=97 (8.2%)) had the highest prevalence between comorbidities. Skin lesions (n= 655 (55.1%)), ophthalmic (n=341 (28.7%)), and cardiac involvement (n=229 (19.3%)) were obtained as the most common extra-pulmonary characteristics of the patients. Amongst 1188 enrolled patients who were not afflicted with Mycobacterium tuberculosis based on smear/culture essay, clinical symptoms, and Chest x-ray screening, 121 (10.2%) cases had detectable amplified DNA for Mycobacterium Tuberculosis extracted from mediastinal lung lymph nodes. Conclusion: In this survey, the mycobacterium genome was detected in almost 1 per 10 case biopsies of sarcoidosis. The remarkable number of cases (n=1188) evaluated in this study was the strength of this study which supported the hypothesis regarding sarcoidosis and mycobacterium genome correlation. Further investigation, such as case-control surveys, is required to better clarify this association.

Keywords: mycobacterium tuberculosis, sarcoidosis, genome, DNA, trans-bronchial needle aspiration

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Authors: Skiker Kaoutar, Mounir Maouene

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Neuroimaging studies have shown that animal and tool concepts rely on distinct networks of brain areas. Animal concepts depend predominantly on temporal areas while tool concepts rely on fronto-temporo-parietal areas. However, the origin of this neurofunctional distinction for processing animal and tool concepts remains still unclear. Here, we address this question from a network perspective suggesting that the neural distinction between animals and tools might reflect the differences in their structural semantic networks. We build semantic networks for animal and tool concepts derived from McRae and colleagues’s behavioral study conducted on a large number of participants. These two networks are thus analyzed through a large number of graph theoretical measures for small-worldness: centrality, clustering coefficient, average shortest path length, as well as resistance to random and targeted attacks. The results indicate that both animal and tool networks have small-world properties. More importantly, the animal network is more vulnerable to targeted attacks compared to the tool network a result that correlates with brain lesions studies.

Keywords: animals, tools, network, semantics, small-worls, resilience to damage

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Authors: Vadim Makarov, Stewart T.Cole

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PBTZ169 is novel drug candidate with high efficacy in animals models, and its combination treatment of PBTZ169 with BDQ and pyrazinamide was shown to be more efficacious than the standard treatment for tuberculosis in a mouse model. The target of PBTZ169 is famous DprE1, an essential enzyme in cell wall biosynthesis. The crystal structure of the DprE1-PBTZ169 complex reveals formation of a semimercaptal adduct with Cys387 in the active site and explains the irreversible inactivation of the enzyme. Furthermore, this drug candidate demonstrated during preclinical research ‘drug like’ properties what made it an attractive drug candidate to treat tuberculosis in humans. During first clinical trials several cohorts of the healthy volunteers were treated by the single doses of PBTZ169 as well as two weeks repeated treatment was chosen for two maximal doses. As expected PBTZ169 was well tolerated, and no significant toxicity effects were observed during the trials. The study of the metabolism shown that human metabolism of PBTZ169 is very different from microbial or animals compound transformation. So main pathway of microbial, mice and less rats metabolism connected with reduction processes, but human metabolism mainly connected with oxidation processes. Due to this difference we observed several metabolites of PBTZ169 in humans with antitubercular activity, and now we can conclude that animal antituberculosis activity of PBTZ169 is a result not only activity of the drug itself, but it is a result of the sum activity of the drug and its metabolites. Direct antimicrobial plasma activity was studied, and such activity was observed for 24 hours after human treatment for some doses. This data gets high chance for good efficacy of PBTZ169 in human for treatment TB infection. Second phase of clinical trials was started summer of 2017 and continues to the present day. Available data will be presented.

Keywords: clinical trials, DprE1, PBTZ169, metabolism

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

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

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

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Authors: Usiobaifo Agharese Rosemary, Osaseri Roseline Oghogho

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Diabetes is a complex group of disease with a variety of causes; it is a disorder of the body metabolism in the digestion of carbohydrates food. The application of machine learning in the field of medical diagnosis has been the focus of many researchers and the use of recognition and classification model as a decision support tools has help the medical expert in diagnosis of diseases. Considering the large volume of medical data which require special techniques, experience, and high diagnostic skill in the diagnosis of diseases, the application of an artificial intelligent system to assist medical personnel in order to enhance their efficiency and accuracy in diagnosis will be an invaluable tool. In this study will propose a diabetes diagnosis model using rough set and K-nearest Neighbor classifier algorithm. The system consists of two modules: the feature extraction module and predictor module, rough data set is used to preprocess the attributes while K-nearest neighbor classifier is used to classify the given data. The dataset used for this model was taken for University of Benin Teaching Hospital (UBTH) database. Half of the data was used in the training while the other half was used in testing the system. The proposed model was able to achieve over 80% accuracy.

Keywords: classifier algorithm, diabetes, diagnostic model, machine learning

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Authors: Gurleen Kour, Mowkshi Khullar, B. K. Chandan, Parvinder Pal Singh, Kushalava Reddy Yumpalla, Gurunadham Munagala, Ram A. Vishwakarma, Zabeer Ahmed

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New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). Apart from in-vitro potency against the target, physiochemical properties and pharmacokinetic properties play an imperative role in the process of drug discovery. We have identified novel nitroimidazole derivatives with potential activity against mycobacterium tuberculosis. One lead candidates, MCD-017, which showed potent activity against H37Rv strain (MIC=0.5µg/ml) and was further evaluated in the process of drug development. Methods: Basic physicochemical parameters like solubility and lipophilicity (LogP) were evaluated. Thermodynamic solubility was determined in PBS buffer (pH 7.4) using LC/MS-MS. The partition coefficient (Log P) of the compound was determined between octanol and phosphate buffered saline (PBS at pH 7.4) at 25°C by the microscale shake flask method. The compound followed Lipinski’s rule of five, which is predictive of good oral bioavailability and was further evaluated for metabolic stability. In-vitro metabolic stability was determined in rat liver microsomes. The hepatotoxicity of the compound was also determined in HepG2 cell line. In vivo pharmacokinetic profile of the compound after oral dosing was also obtained using balb/c mice. Results: The compound exhibited favorable solubility and lipophilicity. The physical and chemical properties of the compound were made use of as the first determination of drug-like properties. The compound obeyed Lipinski’s rule of five, with molecular weight < 500, number of hydrogen bond donors (HBD) < 5 and number of hydrogen bond acceptors(HBA) not more then 10. The log P of the compound was less than 5 and therefore the compound is predictive of exhibiting good absorption and permeation. Pooled rat liver microsomes were prepared from rat liver homogenate for measuring the metabolic stability. 99% of the compound was not metabolized and remained intact. The compound did not exhibit cytoxicity in hepG2 cells upto 40 µg/ml. The compound revealed good pharmacokinetic profile at a dose of 5mg/kg administered orally with a half life (t1/2) of 1.15 hours, Cmax of 642ng/ml, clearance of 4.84 ml/min/kg and a volume of distribution of 8.05 l/kg. Conclusion : The emergence of multi drug resistance (MDR) and extensively drug resistant (XDR) Tuberculosis emphasize the requirement of novel drugs active against tuberculosis. Thus, the need to evaluate physicochemical and pharmacokinetic properties in the early stages of drug discovery is required to reduce the attrition associated with poor drug exposure. In summary, it can be concluded that MCD-017 may be considered a good candidate for further preclinical and clinical evaluations.

Keywords: mycobacterium tuberculosis, pharmacokinetics, physicochemical properties, hepatotoxicity

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Authors: Hyun-Woo Cho

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Unexpected operational events or abnormalities of industrial processes have a serious impact on the quality of final product of interest. In terms of statistical process control, fault detection and diagnosis of processes is one of the essential tasks needed to run the process safely. In this work, nonlinear representation of process measurement data is presented and evaluated using a simulation process. The effect of using different representation methods on the diagnosis performance is tested in terms of computational efficiency and data handling. The results have shown that the nonlinear representation technique produced more reliable diagnosis results and outperforms linear methods. The use of data filtering step improved computational speed and diagnosis performance for test data sets. The presented scheme is different from existing ones in that it attempts to extract the fault pattern in the reduced space, not in the original process variable space. Thus this scheme helps to reduce the sensitivity of empirical models to noise.

Keywords: fault diagnosis, nonlinear technique, process data, reduced spaces

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Authors: Shishen Xie, Yingda L. Xie

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Tuberculosis (TB) is a potentially serious infectious disease that remains a health concern. The Interferon Gamma Release Assay (IGRA) is a blood test to find out if an individual is tuberculous positive or negative. This study applies statistical analysis to the clinical data of interferon-gamma levels of seventy-three subjects who diagnosed pulmonary TB in an anti-tuberculous treatment. Data analysis is performed to determine if there is a significant decline in interferon-gamma levels for the subjects during a period of six months, and to infer if the anti-tuberculous treatment is effective.

Keywords: data analysis, interferon gamma release assay, statistical methods, tuberculosis infection

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Authors: Murat Durucu

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Glaucoma is a condition of irreversible blindness, early diagnosis and appropriate interventions to make the patients able to see longer time. In this study, it addressed that the importance of developing a decision support system for glaucoma diagnosis. Glaucoma occurs when pressure happens around the eyes it causes some damage to the optic nerves and deterioration of vision. There are different levels ranging blindness of glaucoma disease. The diagnosis at an early stage allows a chance for therapies that slows the progression of the disease. In recent years, imaging technology from Heidelberg Retinal Tomography (HRT), Stereoscopic Disc Photo (SDP) and Optical Coherence Tomography (OCT) have been used for the diagnosis of glaucoma. This better accuracy and faster imaging techniques in response technique of OCT have become the most common method used by experts. Although OCT images or HRT precision and quickness, especially in the early stages, there are still difficulties and mistakes are occurred in diagnosis of glaucoma. It is difficult to obtain objective results on diagnosis and placement process of the doctor's. It seems very important to develop an objective decision support system for diagnosis and level the glaucoma disease for patients. By using OCT images and pattern recognition systems, it is possible to develop a support system for doctors to make their decisions on glaucoma. Thus, in this recent study, we develop an evaluation and support system to the usage of doctors. Pattern recognition system based computer software would help the doctors to make an objective evaluation for their patients. It is intended that after development and evaluation processes of the software, the system is planning to be serve for the usage of doctors in different hospitals.

Keywords: decision support system, glaucoma, image processing, pattern recognition

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Authors: Skiker Kaoutar, Mounir Maouene

Abstract:

Neuroimaging studies have shown that animal and tool concepts rely on distinct networks of brain areas. Animal concepts depend predominantly on temporal areas while tool concepts rely on fronto-temporo-parietal areas. However, the origin of this neurofunctional distinction for processing animal and tool concepts remains still unclear. Here, we address this question from a network perspective suggesting that the neural distinction between animals and tools might reflect the differences in their structural semantic networks. We build semantic networks for animal and tool concepts derived from Mc Rae and colleagues’s behavioral study conducted on a large number of participants. These two networks are thus analyzed through a large number of graph theoretical measures for small-worldness: centrality, clustering coefficient, average shortest path length, as well as resistance to random and targeted attacks. The results indicate that both animal and tool networks have small-world properties. More importantly, the animal network is more vulnerable to targeted attacks compared to the tool network a result that correlates with brain lesions studies.

Keywords: animals, tools, network, semantics, small-world, resilience to damage

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Authors: M. D. Antoine

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When a child is diagnosed with an illness, condition, or developmental disorder, the process involved in understanding and accepting this diagnosis can be a very stressful and isolating experience for parents and families. The healthcare providers’ ability to effectively communicate in such situations represents a vital lifeline for parents. In this context, communication becomes a crucial element not only for getting through the period of grief but also for the future. We mobilized the five stages of grief model to summarize existing literature regarding the ways in which the experience ofan autism spectrum disorder diagnosis disclosurealigns with the experience of grief to explore how this can inform best practices for effective communication with parents through the diagnosis disclosure. Fifteen publications met inclusion criteria. Findings from the scoping review of empirical studies show that parents/families experience grief-like emotions during the diagnosis disclosure. However, grief is not an outcome of the encounter itself. In fact, the experience of the encounter can help mitigate the grief experience. The way parents/families receive and react to the ‘news’ depends on their preparedness, knowledge, and the support received through the experience. Individual communication skills, as well as policies and regulations, should be examined to alleviate adverse reactions in this context. These findings highlight the importance of further research into effective parent-provider communication strategies and their place in supporting quality autism care.

Keywords: autism spectrum disorder, autism spectrum disorder diagnosis, diagnosis disclosure, parent-provider communication, parental grief

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Authors: Hyun-Woo Cho

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It is quite important to utilize right time and intelligent production monitoring and diagnosis of industrial processes in terms of quality and safety issues. When compared with monitoring task, fault diagnosis represents the task of finding process variables responsible causing a specific fault in the process. It can be helpful to process operators who should investigate and eliminate root causes more effectively and efficiently. This work focused on the active use of combining a nonlinear statistical technique with a preprocessing method in order to implement practical real-time fault identification schemes for data-rich cases. To compare its performance to existing identification schemes, a case study on a benchmark process was performed in several scenarios. The results showed that the proposed fault identification scheme produced more reliable diagnosis results than linear methods. In addition, the use of the filtering step improved the identification results for the complicated processes with massive data sets.

Keywords: diagnosis, filtering, nonlinear statistical techniques, process monitoring

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Authors: Robert Krause

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Primary progressive aphasia (PPA) is a neurodegenerative disease similar to frontotemporal and semantic dementia, while having a different clinical image and anatomic pathology topography. Nonetheless, they are often included under an umbrella term: frontotemporal lobar degeneration (FTLD). In the study, examples of diagnosing PPA are presented through the multidisciplinary lens of specialists from different fields (neurologists, psychiatrists, clinical speech therapists, clinical neuropsychologists and others) using a variety of diagnostic tools such as MR, PET/CT, genetic screening and neuropsychological and logopedic methods. Thanks to that, specialists can get a better and clearer understanding of PPA diagnosis. The study summarizes the concrete procedures and results of different specialists while diagnosing PPA in a patient of younger middle age and illustrates the importance of multidisciplinary approach to differential diagnosis of PPA.

Keywords: primary progressive aphasia, etiology, diagnosis, younger middle age

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Authors: Akhil Raj Pushparajan, Ranjit Ramachandran, Jijimole Gopi Reji, Ajay Kumar Ramakrishnan

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the leading causes of death by an infectious disease. In spite of the availability of effective drugs and a vaccine, TB is a major health concern and was declared a global emergency by the World Health Organization (WHO). The success of intracellular pathogens like Mtb depends on its ability to overcome the challenging environment in the host. Gene regulation controlled by transcriptional regulators (TRs) plays a crucial role for the bacteria to adapt to the host environment. In vitro studies on gene regulatory mechanisms during dormancy and reactivation have provided insights into the adaptations employed by Mtb to survive in the host. Here we present our efforts to functionally characterize Rv1019, a putative TR of Mtb H37Rv which was found to be present at significantly varying levels during dormancy and reactivation in vitro. The expression of this protein in the dormancy-reactivation model was validated by qRT-PCR and western blot. By DNA- protein interaction studies and reporter assays we found that under normal laboratory conditions of growth this protein behaves as an auto-repressor and tetracycline was found to abrogate this repression by interfering with its ability to bind DNA. Further, by cDNA analysis, we found that this TR is co-transcribed with its downstream genes Rv1020 (mfd) and Rv1021 (mazG) which are involved in DNA damage response in Mtb. Constitutive expression of this regulator in the surrogate host M. smegmatis showed downregulation of the orthologues of downstream genes suggested that Rv1019 could negatively regulate these genes. Our finds also show that M. smegmatis expressing Rv1019 is sensitive to DNA damage suggests the role of this protein in regulating DNA damage response induced by oxidative stress. Because of its role in regulating DNA damage response which may help in the persistence of Mtb, Rv1019 could be used as a prospective target for therapeutic intervention to fight TB.

Keywords: auto-repressor, DNA repair, mycobacterium smegmatis, mycobacterium tuberculosis, tuberculosis

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Authors: Pui Hong Chung, Wing Chi Ho, Jun Li, Cyrus Leung, Ek Yeoh

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Background: Cigarette smoking is associated with poor tuberculosis (TB) outcomes in terms of progression of active TB, relapse of TB and TB-related mortality, but the association with latent tuberculosis infection (LTBI) is unclear. The systematic review conducted aimed at studying the association between active smoking and LTBI, and likelihood of dose-response relationship. Methods: Two independent reviewers searched three electronic databases comprising PudMed, Medline by EBSCOHOST, ExcerptaMedica Database (EMBASE), from inception up to 31st Dec 2015 for studies reporting data on current smoking and the LTBI with tuberculin skin test (TST) or interferon-γ release assays (IGRAs) results, comparing the odds ratios (ORs) of outcome measure of TST or IGRAs among current smokers with 95% confidence intervals (CI). Results: Seven studies were identified, including six cross-sectional studies and one longitudinal cohort study. The outcome measures from three studies were in TST, three studies in IGRAs and one for both tests. For TST, OR ranging from 1.39 to 3.40 (95% CI) with all studies shown positive association between cigarette smoking and LTBI. For IGRAs, OR ranging from 0.47 to 1.89 (95% CI) with one study shown the negative association that might be related to impaired interferon-gamma production in immunosuppressive persons. One identified study demonstrated positive dose-response relationship in TST result. Conclusions: Cigarette smoking is likely to be a risk factor of LTBI. There is the important implication for TB and tobacco control program to halt TB by empowering public health policy. Further study is also needed to provide more evidence of the dose-response model/relationship.

Keywords: latent tuberculosis infection, systematic review, active smoking, model

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Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.

Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT

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Authors: Vagolu S. Krishna, Shan Zheng, Estharla M. Rekha, Luke W. Guddat, Dharmarajan Sriram

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Tuberculosis (TB) remains a major threat to human health. This due to the fact that current drug treatments are less than optimal as well as the rising occurrence of multi drug-resistant and extensively drug-resistant strains of the etiological agent, Mycobacterium tuberculosis (Mt). Given the wide-spread significance of this disease, we have undertaken a design and evaluation program to discover new anti-TB drug leads. Here, our attention is focused on ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway. Importantly, this enzyme is present in bacteria but not in humans, making it an attractive proposition for drug discovery. In the present work, we used high-throughput virtual screening to identify seventeen potential inhibitors of KARI using the Birla Institute of Technology and Science in-house database. Compounds were selected based on high docking scores, which were assigned as the result of favourable interactions between the compound and the active site of KARI. The Ki values for two leads, compounds 14 and 16 are 3.71 and 3.06 µM, respectively for Mt KARI. To assess the mode of binding, 100 ns molecular dynamics simulations for these two compounds in association with Mt KARI were performed and showed that the complex was stable with an average RMSD of less than 2.5 Å for all atoms. Compound 16 showed an MIC of 2.06 ± 0.91 µM and a 1.9 fold logarithmic reduction in the growth of Mt in an infected macrophage model. The two compounds exhibited low toxicity against murine macrophage RAW 264.7 cell lines. Thus, both compounds are promising candidates for development as an anti-TB drug leads.

Keywords: ketol-acid reductoisomerase, macrophage, molecular docking and dynamics, tuberculosis

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Authors: Gina Leisching, Ray-Dean Pietersen, Carel Van Heerden, Paul Van Helden, Ian Wiid, Bienyameen Baker

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The distinguishing factors that characterize the host response to infection with virulent Mycobacterium tuberculosis (M.tb) are largely confounding. We present an infection study with two genetically closely related M.tb strains that have vastly different pathogenic characteristics. The early host response to infection with these detergent-free cultured strains was analyzed through RNAseq in an attempt to provide information on the subtleties which may ultimately contribute to the virulent phenotype. Murine bone marrow-derived macrophages (BMDMs) were infected with either a hyper- (R5527) or hypovirulent (R1507) Beijing M. tuberculosis clinical isolate. RNAseq revealed 69 differentially expressed host genes in BMDMs during comparison of these two transcriptomes. Pathway analysis revealed activation of the stress-induced and growth inhibitory Gadd45 signaling pathway in hypervirulent infected BMDMs. Upstream regulators of interferon activation such as and IRF3 and IRF7 were predicted to be upregulated in hypovirulent-infected BMDMs. Additional analysis of the host immune response through ELISA and qPCR included the use of human THP-1 macrophages where a robust proinflammatory response was observed after infection with the hypervirulent strain. RNAseq revealed two early-response genes (IER3 and SAA3) and two host-defence genes (OASL1 and SLPI) that were significantly upregulated by the hypervirulent strain. The role of these genes under M.tb infection conditions are largely unknown but here we provide validation of their presence with use of qPCR and Western blot. Further analysis into their biological role under infection with virulent M.tb is required.

Keywords: host-response, Mycobacterium tuberculosis, RNAseq, virulence

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Authors: Chetna Khandelwal

Abstract:

This research aims to study the contentions that Farm Animal Sanctuaries pose to human-animal relationships in modernity, which have developed as a result of globalisation of the meat industry and advancements in technology. The sociological history of human-animal relationships in farming is contextualised in order to set a foundation for the follow-up examination of challenges to existing human-(farm)animal relationships by Farm Animal Sanctuaries. The methodology was influenced by relativism, and the method involved three semi-structured small-group interviews, conducted at locations of sanctuaries. The sample was chosen through purposive sampling and varied by location and size of the sanctuary. Data collected were transcribed and qualitatively coded to generate themes. Findings revealed that sanctuary contentions to established human-animal relationships by factory farming could be divided into 4 broad categories – Revealing horrors of factory farming (involving uncovering power relations in agribusiness); transforming relationships with animals (including letting them emotionally heal in accordance with their individual personalities and treating them as partial-pets); educating the public regarding welfare conditions in factory farms as well as animal sentience through practical experience or positive imagery of farm animals, and addressing retaliation made by agribusiness in the form of technologies or discursive strategies. Hence, this research concludes that The human-animal relationship in current times has been characterised by – (ideological and physical) distance from farm animals, commodification due to increased chasing of profits over welfare and exploitation using technological advancements, creating unequal power dynamics that rid animals of any agency. Challenges to this relationship can be influenced by local populations around the sanctuary but not so dependent upon the size of it. This research can benefit from further academic exploration into farm animal sanctuaries and their role in feminist animal rights activism to enrich the ongoing fight against intensive farming.

Keywords: animal rights, factory farming, farm animal sanctuaries, human-animal relationships

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Authors: C. Santhana Krishnan, A. M. Mimi Sakinah, Lakhveer Singh, Zularisam A. Wahid

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This study was initiated to evaluate and optimize the conversion of animal fat from tannery wastes into methyl ester. In the pre-treatment stage, animal fats feedstock was hydrolysed and esterified through solid state fermentation (SSF) using Microbacterium species immobilized onto sand silica matrix. After 72 hours of fermentation, predominant esters in the animal fats were found to be with 83.9% conversion rate. Later, esterified animal fats were transesterified at 3 hour reaction time with 1% NaOH (w/v %), 6% methanol to oil ratio (w/v %) to produce 89% conversion rate. C₁₃ NMR revealed long carbon chain in fatty acid methyl esters at 22.2817-31.9727 ppm. Methyl esters of palmitic, stearic, oleic represented the major components in biodiesel.

Keywords: tannery wastes, fatty animal fleshing, trans-esterification, immobilization, solid state fermentation

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Authors: Ndarusanze Berchmans

Abstract:

This research work focused on the analysis of the observations of tuberculous meningitis in HIV-positive patients who were treated by the Prince Regent Charles Hospital in Bujumbura. A number of 246 seropositive patients were examined by the laboratory of Prince Regent Charles in the period between 2010 and 2015. We did a retrospective study; we used data from the registers of the laboratories mentioned above; the objective was to approach the epidemiological, biological, clinical, and therapeutic characteristics of tuberculosis meningitis infection: 124 women (50.40% of AIDS patients) and 122 men (49.59% of AIDS patients) were subject to the diagnosis by identification of cerebrospinal fluid (CSF). The average age of the patients was 30 years for this period. The population at risk has an average age of between 34 and 42 years for the years between 2010-2015. From 2010 to 2012, cases of opportunistic diseases (e.g., tuberculous meningitis and Cryptococcus neoformans meningitis), often found in immunocompromised, were observed at a high rate; in this period, there was a disturbance of the rhythm providing antiretroviral drugs to people with AIDS. The rate of the two meningitis (tuberculous meningitis and Cryptococcus neoformans meningitis) remained above 10% to gradually decrease until 2015, with the gradual return of antiretrovirals. This period records an overall average of 25 cases of tuberculous meningitis, or a percentage of 10.16%. For the year 2015, there were 4 cases of tuberculous meningitis out of a total of 35 seropositive examined (11.42%). This year's percentage shows that the number of tuberculous meningitis cases has fallen from the rate in previous years. This is the result of the care given by associations against HIV/AIDS to HIV-positive people. This decrease in cases of tuberculous meningitis is due to the acquisition of antiretrovirals by all HIV-positive people treated by hospitals. For the moment, these hospitals are taking care of many AIDS patients by providing them permanently with antiretrovirals; Besides that, there are many patients who are supported by associations whose activities are directed against HIV/AIDS.

Keywords: Cryptococcus neoformans meningitis, tuberculosis meningitis, neurological complications, epidemiology of meningitis

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Authors: Williams A. Adu, Cynthia A. Danquah, Paul P. S. Ossei, Selase Ativui, Michael Ofori, James Asenso, George Owusu

Abstract:

Background Silicosis is an occupational disease of the lung that is caused by chronic exposure to silica dust. There is a higher frequency of co-existence of silicosis with tuberculosis (TB), ultimately resulting in lung fibrosis and respiratory failure. Chronic intake of synthetic drugs has resulted in undesirable side effects. Diosgenin is a steroidal saponin that has been shown to exert a therapeutic effect on lung injury. Therefore, we investigated the ability of diosgenin to reduce the susceptibility of silica-induced TB in rats. Method Silicosis was induced by intratracheal instillation of 50 mg/kg crystalline silica in Sprague Dawley rats. Different doses of diosgenin (1, 10, and 100 mg/kg), Mycobacterium smegmatis and saline were administered for 30 days. Afterwards, 5 of the rats from each group were sacrificed, and the 5 remaining rats in each group, except the control, received Mycobacterium smegmatis. Treatment of diosgenin continued until the 50th day, and the rats were sacrificed at the end of the experiment. The result was analysed using a one-way analysis of variance (ANOVA) with a Graph-pad prism Result At a half-maximal inhibition concentration of 48.27 µM, diosgenin inhibited the growth of Mycobacterium smegmatis. There was a marked decline in the levels of immune cell infiltration and cytokines production. Lactate dehydrogenase and total protein levels were significantly reduced compared to control. There was an increase in the survival rate of the treatment group compared to the control. Conclusion Diosgenin ameliorated silica-induced pulmonary tuberculosis by declining the levels of inflammatory and pro-inflammatory cytokines and, in effect, significantly reduced the susceptibility of rats to pulmonary TB.

Keywords: silicosis, tuberculosis, diosgenin, fibrosis, crystalline silica

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Authors: Mohamed A. Hammad, Dzul Azri Mohamed Noor, Syed Azhar Syed Sulaiman, Majed Ahmed Al-Mansoub, Muhammad Qamar

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There is a progressive increase in the prevalence of early onset Type 2 diabetes mellitus. Early detection of Type 2 diabetes enhances the length and/or quality of life which might result from a reduction in the severity, frequency or prevent or delay of its long-term complications. The study aims to determine the onset age for the first diagnosis of Type 2 diabetes mellitus. A retrospective study conducted in the endocrine clinic at Hospital Pulau Pinang in Penang, Malaysia, January- December 2016. Records of 519 patients with Type 2 diabetes mellitus were screened to collect demographic data and determine the age of first-time diabetes mellitus diagnosis. Patients classified according to the age of diagnosis, gender, and ethnicity. The study included 519 patients with age (55.6±13.7) years, female 265 (51.1%) and male 254 (48.9%). The ethnicity distribution was Malay 191 (36.8%), Chinese 189 (36.4%) and Indian 139 (26.8%). The age of Type 2 diabetes diagnosis was (42±14.8) years. The female onset of diabetes mellitus was at age (41.5±13.7) years, while male (42.6±13.7) years. Distribution of diabetic onset by ethnicity was Malay at age (40.7±13.7) years, Chinese (43.2±13.7) years and Indian (42.3±13.7) years. Diabetic onset was classified by age as follow; ≤20 years’ cohort was 33 (6.4%) cases. Group >20- ≤40 years was 190 (36.6%) patients, and category >40- ≤60 years was 270 (52%) subjects. On the other hand, the group >60 years was 22 (4.2%) patients. The range of diagnosis was between 10 and 73 years old. Conclusion: Malay and female have an earlier onset of diabetes than Indian, Chinese and male. More than half of the patients had diabetes between 40 and 60 years old. Diabetes mellitus is becoming more common in younger age <40 years. The age at diagnosis of Type 2 diabetes mellitus has decreased with time.

Keywords: age of onset, diabetes diagnosis, diabetes mellitus, Malaysia, outpatients, type 2 diabetes, retrospective study

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Authors: Hannah Yael Ephraim

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During reproductive age (between 15 and 44), women are particularly susceptible to psychiatric illness. Depression and anxiety disorders are especially common for women during reproductive age. Women of reproductive age are also at greater risk for multiple physical conditions during this time. Existing literature focuses on the impact of mental health on physical health, showing that people with anxiety and depression repeatedly show greater physical health risk among those with developing chronic medical illness. However, there is limited research on the impact physical health has on mental health in women of reproductive age, a large and vulnerable population. For this reason, the current study seeks to ask the following questions: are women of reproductive age with a diagnosis of a chronic physical condition more likely to experience symptoms of mental illness than women without a diagnosis of a chronic physical condition? Does the type of physical illness relate to signs and symptoms of depression and anxiety? A quasi-experimental research design was implemented to compare the mental health outcomes of women with the diagnosis of chronic medical conditions and women without the diagnosis of a chronic medical condition. Quantitative data was collected through an anonymous ten-minute Qualtrics survey. The survey was sent out through multiple online platforms. The sample includes two groups of women: one group with the diagnosis of a chronic medical illness, and one group without a diagnosis and/or symptoms (N = 541). Participants identify as a woman and are between the ages of 15 and 44. A comparison of women with a diagnosis of a chronic physical condition and those without a diagnosis will be conducted to explore differences in depression and anxiety symptoms between women with and without a chronic medical diagnosis. The impact race, SES, and occupation will also be addressed in relation to anxiety and/or depression in women of reproductive age. This study will further the understanding of the relationship between mental illness in women of reproductive age with chronic medical conditions. The results of this study will have implications for the integration of mental health care in women’s health centers and perhaps training of clinicians and physicians providing psychological and medical care to women of reproductive age.

Keywords: mental health, physical health, reproductive age, women

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Authors: Shamila Manie, Soraya Maart, Ayesha Osman

Abstract:

Introduction: People diagnosed with multidrug resistant pulmonary tuberculosis (MDR-PTB) is subjected to prolonged hospitalization in South Africa. It has thus become essential for research to shift its focus from a purely medical approach, but to include social and environmental factors when looking at the impact of the disease on those affected. Aim: To explore the factors affecting individuals with multi-drug resistant pulmonary tuberculosis during long-term hospitalization using the comprehensive ICF core-sets for obstructive pulmonary disease (OPD) and cardiopulmonary (CPR) conditions at Brooklyn Chest Hospital (BCH). Methods: A quantitative descriptive, cross-sectional study design was utilized. A convenient sample of 19 adults at Brooklyn Chest Hospital were interviewed. Results: Most participants reported a decrease in exercise tolerance levels (b455: n=11). However it did not limit participation. Participants reported that a lack of privacy in the environment (e155) was a barrier to health. The presence of health professionals (e355) and the provision of skills development services (e585) are facilitators to health and well-being. No differences exist in the functional ability of HIV positive and negative participants in this sample. Conclusion: The ICF Core Sets appeared valid in identifying the barriers and facilitators experienced by individuals with MDR-PTB admitted to BCH. The hospital environment must be improved to add to the QoL of those admitted, especially improving privacy within the wards. Although the social grant is seen as a facilitator, greater emphasis must be placed on preparing individuals to be economically active in the labour for when they are discharged.

Keywords: multidrug resistant tuberculosis, MDR ICF core sets, health-related quality of life (HRQoL), hospitalization

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