Search results for: central nervous system tuberculosis

Authors: Laura Bellassen, Idit Shachar

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Multiple sclerosis (MS) is a chronic neurological disorder characterized by demyelination of the central nervous system (CNS), leading to a wide range of physical and cognitive impairments. Myeloid cells in the CNS, such microglia and border associated macrophage cells, participate in the neuroinflammation in MS. Activation of those cells in MS contributes to the inflammatory response in the CNS and recruitment of immune cells in the this compartment. SLAMF5 is a cell surface receptor that functions as a homophilic adhesion molecule, whose signaling can activate or inhibit leukocyte function. In the current study we followed the expression and function of SLAMF5 in myeloid cells in the CNS and in the periphery in the murine model for MS, the experimental autoimmune encephalomyelitis model (EAE). Our results show that SLAMF5 deficiency or blocking decreases the expression of activation molecules and costimulatory molecules such as MHCII and CD80, resulting in delayed onset and reduced progression of the disease. Moreover, blocking SLAMF5 in peripheral monocytes derived from MS patients and iPSC-derived microglia cells, controls the expression of HLA-DR and CD80. Thus, SLAMF5 is a regulator of myeloid cells function and can serve as a therapeutic target in autoimmune disorders as Multiple Sclerosis.

Keywords: multiple sclerosis, EAE model, myeloid cells, new antibody, neuroimmunology

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Authors: Ilham Zaidi, P. Sankara Sarma, Quazi Taufique Ahmed, V. Raman Kutty, Khalid Umer Khayyam, Gurpreet Singh, Abhishek Royal

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Introduction: Tuberculosis is a global public health emergency, but it is particularly acute in India, which has the world's highest tuberculosis burden. Due to overpopulation, lack of sanitation, malnutrition, low living standards, and poor socioeconomic status, among other factors, it is India's most common infectious disease. The long period of treatment is one of the main reasons for considering it as a public health emergency. Consequently, there is an increase in patient noncompliance, which leads to treatment failure, adverse treatment outcomes, and deaths. This could lead to the growth of anti-TB drug resistance. According to the WHO, approximately 558 thousand new cases of Multi-Drug Resistance Tuberculosis were diagnosed worldwide, with 8.5 percent developed Extensively Drug Resistance Tuberculosis. Methodology: This study is a program-based cross-sectional descriptive survey of adult tuberculosis patients enrolled in the Delhi-based Revised National Tuberculosis Program. The study setting was 27 NTEP districts of Delhi. (N=65,893) and Sample size- was 200; the sampling method which is used in the study was the systemic random sampling method. Results: Most of the demographic factors (age, gender, residence, and family type) were not significantly associated with adherence; marital status was found statistically significant with the treatment compliance. Hesitation while telling people about the disease and motivation to strictly follow drug schedule by healthcare workers were other factors where a significant association with drug adherence was observed. The study findings also suggest that provision of food, minimal financial and other moral support from family, counseling, discussion and politeness by healthcare providers might also facilitate adherence. Discussion and Conclusions: For TB treatment, adherence, age, sex, socioeconomic status, types of accommodations, malnutrition, and personal hygiene should all be considered; similar results were observed in previous studies. In the care of TB patients, DOTS services, health workers, and family support play a significant role. According to the country's National Strategic Plan, the Indian government has set a goal of eliminating tuberculosis by 2025 and patients' compliance with TB care and treatment adherence is very crucial to achieve this aim. A cohort study will be able to give a better understanding of factors associated with adherence since this study may have missed some defaulters who were absconding and could not be reached. Important Terms: RNTCP, NTEP, DOTS, DS-TB, DR-TB, RR-TB, MDR-TB, XDR-TB, Treatment failure, Treatment relapse, Treatment adherence.

Keywords: treatment adherence, treatment relapse, treatment failure, drug resistance tuberculosis

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Authors: Kearney Dover, Viviene Temple, Lynneth Stuart-Hill

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Heart Rate Variability (HRV) is the beat-to-beat variation in adjacent heartbeats. HRV is a non-invasive measure of the autonomic nervous system (ANS) and provides information about the sympathetic (SNS) and parasympathetic (PNS) nervous systems. The HRV of a well-conditioned heart is generally high at rest, whereas low HRV has been associated with adverse outcomes/conditions, including congestive heart failure, diabetic neuropathy, depression, and hospital admissions. HRV has received very little research attention among individuals with intellectual disabilities in general or Special Olympic athletes. Purpose: 1) Having a longer post-exercise rest and recovery time to establish how long it takes for the athletes’ HRV components to return to pre-exercise levels, 2) To determine if greater familiarization with the testing processes influences HRV. Participants: Two separate samples of 10 adult Special Olympics athletes will be recruited for 2 separate studies. Athletes will be between 18 and 50 years of age and will be members of Special Olympics BC. Anticipated Findings: To answer why the Special Olympics athletes display poor cardiac responsiveness to changes in autonomic modulation during exercise. By testing the cortisol levels in the athletes, we can determine their stress levels which will then explain their measured HRV.

Keywords: 6MWT, autonomic modulation, cortisol levels, intellectual disability

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Authors: Ragy Raafat Gaber Attaalla

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PIP: This review, based on 2 large-scale studies, discusses the pharmacology and physiology of oral steroid contraceptives (OCs). The pharmacological distinction between synthetic and naturally occurring steroids centers on changes in biological activity dependent on compound formulation and an individual's metabolism. OC mechanism of action is explained as the main prevention of ovulation by interference with gonadotropin-releasing hormone. Since some 52 metabolic alterations have been reported in OC users, these phenomena are dealt with in 3 categories: 1) effects on the primary target organs of the female reproductive tract (ovary, myometrium, endometrium, cervix, vagina, breasts, and hypothalamus), 2) general metabolic effects (serum proteins, carbohydrate metabolism, lipid metabolism, water and electrolyte metabolism, body weight, tryptophan metabolism, and vitamins and minerals), and 3) effects on other organ systems (liver, central nervous system, skin, genitourinary, gastrointestinal tract, eye, immune phenomena, and effect on subsequent fertility). The choice of the proper OC formulation and use of OCs by adolescents are discussed. Assessment of OC safety, contraindications, and patient monitoring are provided.

Keywords: steroid oral contraceptives, ovulation, female reproductive tract, metabolic effects

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Authors: Rosalina Penaloza, Joanna Navarro, Pauline Jolly, Anna Junkins, Carlos Seas, Larissa Otero

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Background: Tuberculosis (TB) case detection in Peru relies on passive case finding. This strategy relies on the assumption that the community is aware that a persistent cough is a possible symptom of TB and that formal health care needs to be sought. Despite its importance, health knowledge specific to TB is underexplored in Peru. This study aimed to assess health literacy and level of TB knowledge among outpatients attending a referral hospital in Lima, Peru. The goal was to ascertain knowledge gaps in key areas relating to TB, to identify and prioritize subgroups for intervention, and to provide insight for policy and community interventions considering health literacy. Methods: An observational cross-sectional study was conducted using a survey to measure sociodemographic factors, tuberculosis knowledge, and health literacy. Bivariate and Multivariate logistic regression was performed to study the associations between variables and to account for potential confounders. The study was conducted at Hospital Cayetano Heredia in Lima, Peru from June – August 2017. Results: 272 participants were included in the analysis. 57.7% knew someone who had had TB before, 9% had had TB in the past. Two weeks a cough was correctly identified as a symptom that could be TB by 69.1%. High TB knowledge was found among 149 (54.8%) participants. High health literacy was found among 193 (71.0%) participants. Health literacy and TB knowledge were not significantly associated (OR 0.9 (95%CI 0.5-1.5)). After controlling for sex, age, district, education, health insurance, frequency of hospital visits and previous TB diagnosis: High TB knowledge was associated with knowing someone with TB (aOR 2.7 (95%CI 1.6-4.7)) and being a public transport driver, (aOR 0.2 (95%CI 0.05-0.9)). Not being poor was the single factor associated with high health literacy (aOR 3.8 (95%CI 1.6-8.9)). Conclusions: TB knowledge was fair, though 30% did not know the most important symptom of TB. Tailoring educational strategies to risk groups may enhance passive case detection especially amongst transport workers in Lima, Peru.

Keywords: health literacy, Peru, tuberculosis, tuberculosis knowledge

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Authors: Ya-Chi Yu, Pei-Syuan Ruan, Shao-Wen Chen, Yu-Hsien Chang, Jin-Der Lee, Jong-Rong Wang, Chunkuan Shih

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This study analyzed the transient signals of central region void fraction of air-water two-phase flow in a 3x3 rod bundle. Experimental tests were carried out utilizing a vertical rod bundle test section along with a set of air-water supply/flow control system, and the transient signals of the central region void fraction were collected through the electrical conductivity sensors as well as visualized via high speed photography. By converting the electric signals, transient void fraction can be obtained through the voltage ratios. With a fixed superficial water velocity (J_f=0.094 m/s), two different superficial air velocities (J_g=0.094 m/s and 0.236 m/s) were tested and presented, which were corresponding to the flow conditions of bubbly flows and cap/slug flows, respectively. The time averaged central region void fraction was obtained as 0.109-0.122 with 0.028 standard deviation for the selected bubbly flow and 0.188-0.221with 0.101 standard deviation for the selected cap/slug flow, respectively. Through Fast Fourier Transform (FFT) analysis, no clear frequency peak was found in bubbly flow, while two dominant frequencies were identified around 1.6 Hz and 2.5 Hz in the present cap/slug flow.

Keywords: central region, rod bundles, transient void fraction, two-phase flow

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Authors: Amal M. Alrayes

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Data and system quality play a central role in organizational success, and the quality of any existing information system has a major influence on the effectiveness of overall system performance.Given the importance of system and data quality to an organization, it is relevant to highlight their importance on organizational performance in the Kingdom of Bahrain. This research aims to discover whether system quality and data quality are related, and to study the impact of system and data quality on organizational success. A theoretical model based on previous research is used to show the relationship between data and system quality, and organizational impact. We hypothesize, first, that system quality is positively associated with organizational impact, secondly that system quality is positively associated with data quality, and finally that data quality is positively associated with organizational impact. A questionnaire was conducted among public and private organizations in the Kingdom of Bahrain. The results show that there is a strong association between data and system quality, that affects organizational success.

Keywords: data quality, performance, system quality, Kingdom of Bahrain

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Authors: Shao-Hsuan Chien, Ju-Hui Fu

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Parkinson’s disease (PD) is a degenerative disorder of the central nervous system that is characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta and motor impairment. Aggregation of α-synuclein in neuronal cells plays a key role in this disease. At present, therapeutics for PD provides moderate symptomatic benefit but is not able to delay the development of this disease. Current efforts for the treatment of PD are to identify new drugs that show slow or arrest progressive course of PD by interfering with a disease-specific pathogenetic process in PD patients. Maackiain is a bioactive compound isolated from the roots of the Chinese herb Sophora flavescens. The purpose of the present study was to assess the potential for maackiain to ameliorate PD in Caenorhabditis elegans models. Our data reveal that maackiain prevents α-synuclein accumulation in the transgenic Caenorhabditis elegans model and also improves dopaminergic neuron degeneration, food-sensing behavior, and life-span in 6-hydroxydopamine-induced Caenorhabditis elegans model, thus indicating its potential as a candidate antiparkinsonian drug.

Keywords: maackiain, Parkinson’s disease, dopaminergic neurons, α-Synuclein

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Authors: Syed Asif Hassan, Tabrej Khan

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Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

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Authors: Akinsola Oluwatosin, Udofia Samuel, Odofin Mayowa

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The study is aimed at assessing the Geographic Information System (GIS)-based spatial analysis of Survival Pattern and Treatment Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) cases for Lagos, Nigeria, with an objective to inform priority areas for public health planning and resource allocation. Multi-drug resistant tuberculosis (MDR-TB) develops due to problems such as irregular drug supply, poor drug quality, inappropriate prescription, and poor adherence to treatment. The shapefile(s) for this study were already georeferenced to Minna datum. The patient’s information was acquired on MS Excel and later converted to . CSV file for easy processing to ArcMap from various hospitals. To superimpose the patient’s information the spatial data, the addresses was geocoded to generate the longitude and latitude of the patients. The database was used for the SQL query to the various pattern of the treatment. To show the pattern of disease spread, spatial autocorrelation analysis was used. The result was displayed in a graphical format showing the areas of dispersing, random and clustered of patients in the study area. Hot and cold spot analysis was analyzed to show high-density areas. The distance between these patients and the closest health facility was examined using the buffer analysis. The result shows that 22% of the points were successfully matched, while 15% were tied. However, the result table shows that a greater percentage of it was unmatched; this is evident in the fact that most of the streets within the State are unnamed, and then again, most of the patients are likely to supply the wrong addresses. MDR-TB patients of all age groups are concentrated within Lagos-Mainland, Shomolu, Mushin, Surulere, Oshodi-Isolo, and Ifelodun LGAs. MDR-TB patients between the age group of 30-47 years had the highest number and were identified to be about 184 in number. The outcome of patients on ART treatment revealed that a high number of patients (300) were not ART treatment while a paltry 45 patients were on ART treatment. The result shows the Z-score of the distribution is greater than 1 (>2.58), which means that the distribution is highly clustered at a significance level of 0.01.

Keywords: tuberculosis, patients, treatment, GIS, MDR-TB

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Authors: Sang-Myung Jung, Jeong Hyun Ju, Gwang Heum Yoon, Hwa Sung Shin

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Central nervous system (CNS) consists of neuronal cell and supporting cells. Astrocytes are the most common supporting cells and play roles in metabolism between neurons and blood vessel. For this function, engineered astrocytes have been studied as a therapeutic source for CNS injury. In neural tissue engineering, nanofiber has been suggested as an effective scaffold for providing structure and mechanical properties influencing physiology. Cellulose acetate (CA) has been investigated for material to fabricate scaffold because of its biocompatibility, biodegradability and fine thermal stability. In this research, CA nanofiber was modified via heat treatment and its effect on astrocyte activity was evaluated. Adhesion and viability of astrocyte were increased in proportion to stiffness. Additionally, expression of GFAP, a marker of astrocyte activation, was increased via stiffness of scaffold. This research suggests a simple modification method to change stiffness of CA nanofiber and shows cellular behavior affecting stiffness of three-dimensional scaffold independently. For the results, we highlight that the stiffness is a factor to regulate astrocyte activity.

Keywords: astrocyte, cellulose acetate, cell therapy, stiffness of scaffold

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Authors: Evgeny A. Ermakov, Lyudmila P. Smirnova, Valentina N. Buneva

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Schizophrenia associated with dysregulation of neurotransmitter processes in the central nervous system and disturbances in the humoral immune system resulting in the formation of antibodies (Abs) to the various components of the nervous tissue. Abs to different neuronal receptors and DNA were detected in the blood of patients with schizophrenia. Abs hydrolyzing DNA were detected in pool of polyclonal autoantibodies in autoimmune and infectious diseases, such catalytic Abs were named abzymes. It is believed that DNA-hydrolyzing abzymes are cytotoxic, cause nuclear DNA fragmentation and induce cell death by apoptosis. Abzymes with DNAase activity are interesting because of the mechanism of formation and the possibility of use as diagnostic markers. Therefore, in our work we have set following goals: to determine the level anti-DNA Abs in the serum of patients with schizophrenia and to study DNA-hydrolyzing activity of IgG of patients with schizophrenia. Materials and methods: In our study there were included 41 patients with a verified diagnosis of paranoid or simple schizophrenia and 24 healthy donors. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the serum proteins on protein G-Sepharose and gel filtration. The levels of anti-DNA Abs were determined using ELISA. DNA-hydrolyzing activity was detected as the level of supercoiled pBluescript DNA transition in circular and linear forms, the hydrolysis products were analyzed by agarose electrophoresis followed by ethidium bromide stain. To correspond the registered catalytic activity directly to the antibodies we carried out a number of strict criteria: electrophoretic homogeneity of the antibodies, gel filtration (acid shock analysis) and in situ activity. Statistical analysis was performed in ‘Statistica 9.0’ using the non-parametric Mann-Whitney test. Results: The sera of approximately 30% of schizophrenia patients displayed a higher level of Abs interacting with single-stranded (ssDNA) and double-stranded DNA (dsDNA) compared with healthy donors. The average level of Abs interacting with ssDNA was only 1.1-fold lower than that for interacting with dsDNA. IgG of patient with schizophrenia were shown to possess DNA hydrolyzing activity. Using affinity chromatography, electrophoretic analysis of isolated IgG homogeneity, gel filtration in acid shock conditions and in situ DNAse activity analysis we proved that the observed activity is intrinsic property of studied antibodies. We have shown that the relative DNAase activity of IgG in patients with schizophrenia averaged 55.4±32.5%, IgG of healthy donors showed much lower activity (average of 9.1±6.5%). It should be noted that DNAase activity of IgG in patients with schizophrenia with a negative symptoms was significantly higher (73.3±23.8%), than in patients with positive symptoms (43.3±33.1%). Conclusion: Anti-DNA Abs of patients with schizophrenia not only bind DNA, but quite efficiently hydrolyze the substrate. The data show a correlation with the level of DNase activity and leading symptoms of patients with schizophrenia.

Keywords: anti-DNA antibodies, abzymes, DNA hydrolysis, schizophrenia

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Authors: Hua Cao, Laurent Peyrodie, Olivier Agnani, Cecile Donze

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Multiple sclerosis (MS) is a disease, which affects the central nervous system, and causes balance problem. In clinical, this disorder is usually evaluated using static posturography. Some linear or nonlinear measures, extracted from the posturographic data (i.e. center of pressure, COP) recorded during a balance test, has been used to analyze postural control of MS patients. In this study, the trend (TREND) and the sample entropy (SampEn), two nonlinear parameters were chosen to investigate their relationships with the expanded disability status scale (EDSS) score. Forty volunteers with different EDSS scores participated in our experiments with eyes open (EO) and closed (EC). TREND and two types of SampEn (SampEn1 and SampEn2) were calculated for each combined COP’s position signal. The results have shown that TREND had a weak negative correlation to EDSS while SampEn2 had a strong positive correlation to EDSS. Compared to TREND and SampEn1, SampEn2 showed a better significant correlation to EDSS and an ability to discriminate the MS patients in the EC case. In addition, the outcome of the study suggests that the multi-dimensional nonlinear analysis could provide some information about the impact of disability progression in MS on dynamics of the COP data.

Keywords: balance, multiple sclerosis, nonlinear analysis, postural sway

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Authors: Mohsen Shirani, Micaela Demichela

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Food supply chain is one of the most complex supply chain networks due to its perishable nature and customer oriented products, and food safety is the major concern for this industry. IT system could help to minimize the production and consumption of unsafe food by controlling and monitoring the entire system. However, there have been many issues in adoption of IT system in this industry specifically within SMEs sector. With this regard, this study presents a novel approach to use IT and tractability systems in the food supply chain, using application of RFID and central database.

Keywords: food supply chain, IT system, safety, SME

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Authors: Alireza Assareh, Fatemeh Havas Beigi, Mohammad Vafaee Yeganeh

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The present study is conducted to investigate the relationship between organizational culture and the establishment of knowledge management in the Central Insurance of Iran. The research results revealed that there is a significant positive relationship between organizational culture and its elements that include management support, organizational belonging, individual innovation, and leadership style and the establishment of knowledge management in the central insurance of Iran and that there isn’t any significant relationship between conflict resolution and the establishment of knowledge management in the central insurance of Iran.

Keywords: organizational culture, knowledge management, central insurance of Iran, individual innovation

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Authors: Emmanuel Abban Sagoe

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A proper functioning of the Central Nervous System ensures that we are able to accomplish just about everything we do as human beings such as walking, breathing, running, etc. Myelinated neurons throughout the body which transmit signals at high speeds facilitate these actions. In the case of MS, the body’s immune system attacks the myelin sheath surrounding the neurons and overtime destroys the myelin sheaths. Depending upon where the destruction occurs in the brain symptoms can vary from person to person. Fatigue is, however, the biggest problem encountered by an MS sufferer. It is very often described as the bedrock upon which other symptoms of MS such challenges in balance and coordination, dizziness, slurred speech, etc. may occur. Classifying and distinguishing between perceptions based fatigue and performance based fatigability is key to identifying appropriate treatment options for patients. Objective methods for assessing motor fatigability is also key to providing clinicians and physiotherapist with critical information on the progression of the symptom. This study tested if the Fatigue Index Kliniken Schmieder assessment tool can detect fatigability as seen in MS patients when healthy subjects with no known history of neurological pathology mimic abnormal gaits. Thirty three healthy adults between ages 18-58years volunteered as subjects for the study. The subjects, strapped with RehaWatch sensors on both feet, completed 6 gait protocols of normal and mimicked fatigable gaits for 60 seconds per each gait and at 1.38889m/s treadmill speed following clear instructions given.

Keywords: attractor attributes, fatigue index Kliniken Schmieder, gait variability, movement pattern

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Authors: Emmanuel Kamal Aziz Saba, Hussein Al-Moghazy Sultan

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The aim of this study was to evaluate clinically and electro physiologically the autonomic nervous system changes associated with rheumatoid arthritis (RA). The present study included 25 patients with RA [22 women (88%)] and 30 apparently healthy control subjects [27 women (90%)]. A thorough clinical examination was carried out. Disease activity and functional disability were assessed. Tests for assessment of autonomic functions include active and passive orthostatic stress tests, and sympathetic skin response (SSR). The presence of abnormality in 2 tests or more was a clue for the presence of autonomic neuropathy (AN). Sural sensory nerve conduction study and posterior tibial motor nerve conduction study were done. There was a statistically significant decrease in standing systolic and diastolic blood pressure (BP) components of the active orthostatic stress test and SSR amplitude as well as statistically significant prolongation of SSR latency of RA patients when compared to control. Three patients (12%) had clinical symptoms suggestive of AN; increased to 14 patients (56 %) when orthostatic stress tests and SSR were utilized. There were no statistically significant differences between patients with different disease activity score 28 with 4 variables grades of RA activity and SSR latency and amplitude. There were no statistically significant differences between patients with different Stanford Health Assessment Questionnaire Disability Index grades of RA functional disability and SSR latency and amplitude. In conclusion, autonomic neuropathy is a common extra-articular manifestation of RA affecting sympathetic and parasympathetic fibers.

Keywords: autonomic neuropathy, orthostatic stress test, rheumatoid arthritis, sympathetic skin response

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Authors: Ssembatya Joseph Mary

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Introduction: Cryptococcal infection in the Central Nervous System (CNS) is frequently seen in human immunodeficiency virus (HIV) patients and others with low immunity as an opportunistic fungal infection. However, CNS cryptococcal granuloma (cryptococcoma) in immunocompetent patients is rare. We present a case of CNS cryptococcoma in an immunocompetent patient and review the literature to illustrate the diagnosis and treatment of such lesions. Case presentation: A 62-year-old, HIV-negative, immunocompetent female patient with no known chronic illness presented with 5 months history of a progressive headache associated with on and off episodic generalized tonic-clonic convulsions. She had been to several hospitals before she was referred to our center with a diagnosis of a brain tumor. Before referral and despite a negative CSF analysis result, she had received treatment for bacterial meningitis with no success. At Mbarara Regional Referral Hospital (MRRH), she had surgery with an excision biopsy which showed features consistent with cryptococcosis on histology. The patient had a successful adjuvant treatment with antifungal drugs following surgery. Conclusion: The diagnosis of a parasitic CNS infection, particularly cryptococcal infection mimicking neoplastic lesions in an immunocompetent patient, was unusual. Surgical management of such lesions from different reports has a bad outcome and management remains totally conservative.

Keywords: Cryptococcal meningitis, immunocompetent patient, Uganda, low resource setting

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Authors: R. Bhattu Babajee, Marie Sandrine Estelle Benoit

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The past decades have witnessed a considerable institutional shift towards Central Bank Independence across economies of the world. The motivation behind such a change is the acceptance that increased central bank autonomy has the power of alleviating inflation bias. Hence, studying whether Central Bank Independence acts as a significant factor behind the price stability in the African economies or whether this macroeconomic aim in these countries result from other economic, political or social factors is a pertinent issue. The main research objective of this paper is to assess the relationship between central bank autonomy and inflation in African economies where inflation has proved to be a serious problem. In this optic, we shall measure the degree of CBI in Africa by computing the turnover rates of central banks governors thereby studying whether decisions made by African central banks are affected by external forces. The purpose of this study is to investigate empirically the association between Central Bank Independence (CBI) and inflation for 10 African economies over a period of 17 years, from 1995 to 2012. The sample includes Botswana, Egypt, Ghana, Kenya, Madagascar, Mauritius, Mozambique, Nigeria, South Africa, and Uganda. In contrast to empirical research, we have not been using the usual static panel model for it is associated with potential mis specification arising from the absence of dynamics. To this issue a dynamic panel data model which integrates several control variables has been used. Firstly, the analysis includes dynamic terms to explain the tenacity of inflation. Given the confirmation of inflation inertia, that is very likely in African countries there exists the need for including lagged inflation in the empirical model. Secondly, due to known reverse causality between Central Bank Independence and inflation, the system generalized method of moments (GMM) is employed. With GMM estimators, the presence of unknown forms of heteroskedasticity is admissible as well as auto correlation in the error term. Thirdly, control variables have been used to enhance the efficiency of the model. The main finding of this paper is that central bank independence is negatively associated with inflation even after including control variables.

Keywords: central bank independence, inflation, macroeconomic variables, price stability

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Authors: A. Nuchitprasittichai, N. Lerdritsirikoon, T. Khamsing

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Simulation modeling can be used to solve real world problems. It provides an understanding of a complex system. To develop a simplified model of process simulation, a suitable experimental design is required to be able to capture surface characteristics. This paper presents the experimental design and algorithm used to model the process simulation for optimization problem. The CO₂ liquefaction based on external refrigeration with two refrigeration circuits was used as a simulation case study. Latin Hypercube Sampling (LHS) was purposed to combine with existing Central Composite Design (CCD) samples to improve the performance of CCD in generating the second order model of the system. The second order model was then used as the objective function of the optimization problem. The results showed that adding LHS samples to CCD samples can help capture surface curvature characteristics. Suitable number of LHS sample points should be considered in order to get an accurate nonlinear model with minimum number of simulation experiments.

Keywords: central composite design, CO2 liquefaction, latin hypercube sampling, simulation-based optimization

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Authors: Neslihan Demirci, Serdar Durdağı

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Mycobacterium tuberculosis is still a worldwide disease-causing agent that, according to WHO, led to the death of 1.5 million people from tuberculosis (TB) in 2020. The bacteria reside in macrophages located specifically in the lung. There is a known quadruple drug therapy regimen for TB consisting of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Over the past 60 years, there have been great contributions to treatment options, such as recently approved delamanid (OPC67683) and bedaquiline (TMC207/R207910), targeting mycolic acid and ATP synthesis, respectively. Also, there are natural compounds that can block the tryptophanyl-tRNA synthetase (TrpRS) enzyme, chuangxinmycin, and indolmycin. Yet, already the drug resistance is reported for those agents. In this study, the newly released TrpRS enzyme structure is investigated for potential inhibitor drugs from already synthesized molecules to help the treatment of resistant cases and to propose an alternative drug for the quadruple drug therapy of tuberculosis. Maestro, Schrodinger is used for docking and molecular dynamic simulations. In-house library containing ~8000 compounds among FDA-approved indole-containing compounds, a total of 57 obtained from the ChemBL were used for both ATP and tryptophan binding pocket docking. Best of indole-containing 57 compounds were subjected to hit expansion and compared later with virtual screening workflow (VSW) results. After docking, VSW was done. Glide-XP docking algorithm was chosen. When compared, VSW alone performed better than the hit expansion module. Best scored compounds were kept for ten ns molecular dynamic simulations by Desmond. Further, 100 ns molecular dynamic simulation was performed for elected molecules according to Z-score. The top three MMGBSA-scored compounds were subjected to steered molecular dynamic (SMD) simulations by Gromacs. While SMD simulations are still being conducted, ponesimod (for multiple sclerosis), vilanterol (β₂ adrenoreceptor agonist), and silodosin (for benign prostatic hyperplasia) were found to have a significant affinity for tuberculosis TrpRS, which is the propulsive force for the urge to expand the research with in vitro studies. Interestingly, top-scored ponesimod has been reported to have a side effect that makes the patient prone to upper respiratory tract infections.

Keywords: drug repurposing, molecular dynamics, tryptophanyl-tRNA synthetase, tuberculosis

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Authors: Ali Bayram, Burak Uz, Ilhan Dolasik, Remzi Yiğiter

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The GABARAP (GABAA-receptor-associated protein) family consists of GABARAP, GABARAPL1 (GABARAP-like 1) and GABARAPL2 (GABARAP-like 2). GABARAPL1, like GABARAP, was described to interact with both GABAA receptor and tubulin, and to be involved in intracellular GABAA receptor trafficking and promoting tubulin polymerization. In addition, GABARAPL1 is thought to be involved in various physiological (autophagosome closure, regulation of circadian rhythms) and/or pathological mechanisms (cancer, neurodegeneration). Alzheimer’s disease (AD) is a progressive neuro degenerative disorder characterized with impaired cognitive functions. Disruption of the GABAergic neuro transmission as well as cholinergic and glutamatergic interactions, may also be involved in the pathogenesis of AD. GABARAPL1 presents a regulated tissue expression and is the most expressed gene among the GABARAP family members in the central nervous system. We, herein, conducted a study to investigate the GABARAPL1 mRNA expression levels in patients with AD. 50 patients with AD and 49 control patients were enrolled to the present study. Messenger RNA expression levels of GABARAPL1 were detected by real-time polymerase chain reaction. GABARAPL1 mRNA expression in AD / control patients was 0,495 (95% confidence interval: 0,404-0,607), p= 0,00000002646. Reduced activity of GABARAPL1 gene might play a role, at least partly, in the pathophysiology of AD.

Keywords: Alzheimer’s disease, GABARAPL1, mRNA expression, RT-PCR

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Authors: Khalid Javed, Rashid Mahmood

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The constitution empowers the Federal Government to collect taxes on income other than agricultural income, taxes on capital value, customs, excise duties and sales taxes. The Central Board of Revenue (CBR) and its subordinate departments administer the tax system. Each of the three principal taxes has a different history and different set of issues. For a large number of income tax payers the core of the business process is pre-audit and assessment by a tax official. This process gives considerable discretion to tax officials, with potential for abuse. Moreover, this process is also not tenable as the number of taxpayers increase. The report is focused on a total overhaul of the process and organization of income tax. Sales tax is recent and its process and organization is adjusted to the needs of an expanding tax base. These are based on self-assessment and selective audit. Similarly, in customs the accent is on accelerating and broadening the changes begun in recent years. Before long, central excise will be subsumed in sales tax. During the nineties, despite many changes in the tax regime and introduction of withholding and presumptive taxes, Federal Government tax to GDP ratio has varied narrowly around eleven percent. The tax base has grown but still remains narrow and skewed. The number of income tax filers is around one million.

Keywords: central board of revenue, GDP, sale tax, income tax

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Authors: Shima Mahmoudi, Babak Pourakbari, Setareh Mamishi, Mostafa Teymuri, Majid Marjani

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Although cytokine analysis has greatly contributed to the understanding of tuberculosis (TB) pathogenesis, data on cytokine profiles that might distinguish progression from latency of TB infection are scarce. Since PE/PPE proteins are known to induce strong humoral and cellular immune responses, the aim of this study was to evaluate the diagnostic potential of interleukin-2 (IL-2) as biomarker after specific antigen stimulation with PE35 and PPE68 for the discrimination of active and latent tuberculosis infection (LTBI). The production of IL-2 was measured in the antigen-stimulated whole-blood supernatants following stimulation with recombinant PE35 and PPE68. All the patients with active TB and LTBI had positive QuantiFERON-TB Gold in Tube test. The level of IL-2 following stimulation with recombinant PE35 and PPE68 were significantly higher in LTBI group than in patients with active TB infection or control group. The discrimination performance (assessed by the area under ROC curve) for IL-2 following stimulation with recombinant PE35 and PPE68 between LTBI and patients with active TB were 0.837 (95%CI: 0.72-0.97) and 0.75 (95%CI: 0.63-0.89), respectively. Applying the 12.4 pg/mL cut-off for IL-2 induced by PE35 in the present study population resulted in sensitivity of 78%, specificity of 78%, PPV of 78% and NPV of 100%. In addition, a sensitivity of 81%, specificity of 70%, PPV of 67% and 87% of NPV was reported based on the 4.4 pg/mL cut-off for IL-2 induced by PPE68. In conclusion, peptides of the antigen PE35 and PPE68, absent from commonly used BCG strains, stimulated strong IL-2- positive T cell responses in patients with LTBI. This study confirms IL-2 induced by PE35 and PPE68 as a sensitive and specific biomarker and highlights IL-2 as new promising adjunct markers for discriminating of LTBI and Active TB infection.

Keywords: IL-2, PE35, PPE68, tuberculosis

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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: Anne-Lena Kampen, Øivind Kure

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Machine learning (ML) can be implemented in Wireless Sensor Networks (WSNs) as a central solution or distributed solution where the ML is embedded in the nodes. Embedding improves privacy and may reduce prediction delay. In addition, the number of transmissions is reduced. However, quality factors such as prediction accuracy, fault detection efficiency and coordinated control of the overall system suffer. Here, we discuss and highlight the trade-offs that should be considered when choosing between embedding and centralized ML, especially for multihop networks. In addition, we present estimations that demonstrate the energy trade-offs between embedded and centralized ML. Although the total network energy consumption is lower with central prediction, it makes the network more prone for partitioning due to the high forwarding load on the one-hop nodes. Moreover, the continuous improvements in the number of operations per joule for embedded devices will move the energy balance toward embedded prediction.

Keywords: central machine learning, embedded machine learning, energy consumption, local machine learning, wireless sensor networks, WSN

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Authors: A. A. Agbor, Jean Joel R. Bigna, Serges Clotaire Billong, Mathurin Cyrille Tejiokem, Gabriel L. Ekali, Claudia S. Plottel, Jean Jacques N. Noubiap, Hortence Abessolo, Roselyne Toby, Sinata Koulla-Shiro

Abstract:

Background: Contributors to fatal outcomes in patients undergoing tuberculosis (TB) treatment in the setting of HIV co-infection are poorly characterized, especially in sub-Saharan Africa. Our study’s aim was to assess factors associated with death in TB/HIV co-infected patients during the first 6 months their TB treatment. Methods: We conducted a tertiary-care hospital-based retrospective cohort study from January 2006 to December 2013 at the Yaoundé Central Hospital, Cameroon. We reviewed medical records to identify hospitalized co-infected TB/HIV patients aged 15 years and older. Death was defined as any death occurring during TB treatment, as per the World Health Organization’s recommendations. Logistic regression analysis identified factors associated with death. Magnitudes of associations were expressed by adjusted odds ratio (aOR) with 95% confidence interval. A p value < 0.05 was considered statistically significant. Results: The 337 patients enrolled had a mean age of 39.3 (+/- 10.3) years and more (54.3%) were women. TB treatment outcomes included: treatment success in 60.8% (n=205), death in 29.4% (n=99), not evaluated in 5.3% (n=18), loss to follow-up in 5.3% (n=14), and failure in 0.3% (n=1) . After exclusion of patients lost to follow-up and not evaluated, death in TB/HIV co-infected patients during TB treatment was associated with: a TB diagnosis made before national implementation of guidelines regarding initiation of antiretroviral therapy (aOR = 2.50 [1.31-4.78]; p = 0.006), the presence of other AIDS-defining infections (aOR = 2.73 [1.27-5.86]; p = 0.010), non-AIDS comorbidities (aOR = 3.35 [1.37-8.21]; p = 0.008), not receiving co-trimoxazole prophylaxis (aOR = 3.61 [1.71-7.63]; p = 0.001), not receiving antiretroviral therapy (aOR = 2.45 [1.18-5.08]; p = 0.016), and CD4 cell counts < 50 cells/mm3 (aOR = 16.43 [1.05-258.04]; p = 0.047). Conclusions: The success rate of anti-tuberculosis treatment among hospitalized TB/HIV co-infected patients in our setting is low. Mortality in the first 6 months of treatment was high and strongly associated with specific clinical factors including states of greater immunosuppression, highlighting the urgent need for targeted interventions, including provision of anti-retroviral therapy and co-trimoxazole prophylaxis in order to enhance patient outcomes.

Keywords: TB/HIV co-infection, death, treatment outcomes, factors

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Authors: Megumi Nishida, Naoya Motegi, Takurou Kikuchi, Tomoko Tokumura

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In recent years, power system has been changed and flexible power pricing system such as demand response has been sought in Japan. The demand response system is simple in the household sector and the owner, decision-maker, can gain the benefits of power saving. On the other hand, the execution of the demand response in the office building is more complex than household because various people such as owners, building administrators and occupants are involved in making decisions. While the owners benefit from the demand saving, the occupants are forced to be exposed to demand-saved environment certain benefits. One of the reasons is that building systems are usually centralized control and each occupant cannot choose either participate demand response event or not, and contribution of each occupant to demand response is unclear to provide incentives. However, the recent development of IT and building systems enables the personalized control of office environment where each occupant can control the lighting level or temperature around him or herself. Therefore, it can be possible to have a system which each occupant can make a decision of demand response participation in office building. This study investigates the personal behavior upon demand response requests, under the condition where each occupant can adjust their brightness individually in their workspace. Once workers participate in the demand response, their task lights are automatically turned off. The participation rates in the demand response events are compared between four groups which are divided by different motivation, the presence or absence of incentives and the way of participation. The result shows that there are the significant differences of participation rates in demand response event between four groups. The way of participation has a large effect on the participation rate. ‘Opt-out’ group, where the occupants are automatically enrolled in a demand response event if they don't express non-participation, will have the highest participation rate in the four groups. The incentive has also an effect on the participation rate. This study also reports that the impact of low illumination office environment on the occupants, such as stress or fatigue. The electrocardiogram and the questionnaire are used to investigate the autonomic nervous activity and subjective symptoms about the fatigue of the occupants. There is no big difference between dim workspace during demand response event and bright workspace in autonomic nervous activity and fatigue.

Keywords: demand response, illumination, questionnaire, electrocardiogram

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Authors: Abdul Matin, Salik Nawaz, Suk-Yul Jung

Abstract:

Balamuthia mandrillaris is well known to cause fatal Balamuthia amoebic encephalitis (BAE). Amoebic transmission into the central nervous system (CNS), haematogenous spread is thought to be the prime step, followed by blood-brain barrier (BBB) dissemination. Macrophages are considered to be the foremost line of defense and present in excessive numbers during amoebic infections. The aim of the present investigation was to evaluate the effects of macrophages alone or primed with cytokines on the biological characteristics of Balamuthia in vitro. Using human brain microvascular endothelial cells (HBMEC), which constitutes the BBB, we have shown that Balamuthia demonstrated > 90% binding and > 70% cytotoxicity to host cells. However, macrophages further increased amoebic binding and Balamuthia-mediated cell cytotoxicity. Furthermore, macrophages exhibited no amoebicidal effect against Balamuthia. Zymography assay demonstrated that macrophages exhibited no inhibitory effect on proteolytic activity of Balamuthia. Overall, to our best knowledge, we have shown for the first time macrophages has no inhibitory effects on the biological properties of Balamuthia in vitro. This also strengthened the concept that how and why Balamuthia can cause infections in both immuno-competent and immuno-compromised individuals.

Keywords: Balamuthia mandrillaris, macrophages, cytokines, human brain microvascular endothelial cells, Balamuthia amoebic encephalitis

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Authors: Shraddha Acharya, Sharad Kumar Sharma, Ratna Bhattarai, Bhagwan Maharjan, Deepak Dahal, Serpahine Kaminsa

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Background: Drug-resistant (DR) tuberculosis (TB) continues to be a threat in Nepal, with an estimated 2800 new cases every year. The treatment of DR-TB with second line TB drugs is complex and takes longer time with comparatively lower treatment success rate than drug-susceptible TB. Delay in treatment initiation for DR-TB patients might further result in unfavorable treatment outcomes and increased transmission. This study thus aims to determine median time taken to initiate second-line treatment among Rifampicin Resistant (RR) diagnosed TB patients and to assess the proportion of treatment delays among various type of DR-TB cases. Method: A retrospective cohort study was done using national routine electronic data (DRTB and TB Laboratory Patient Tracking System-DHIS2) on drug resistant tuberculosis patients between January 2020 and December 2022. The time taken for treatment initiation was computed as– days from first diagnosis as RR TB through Xpert MTB/Rif test to enrollment on second-line treatment. The treatment delay (>7 days after diagnosis) was calculated. Results: Among total RR TB cases (N=954) diagnosed via Xpert nationwide, 61.4% were enrolled under shorter-treatment regimen (STR), 33.0% under longer treatment regimen (LTR), 5.1% for Pre-extensively drug resistant TB (Pre-XDR) and 0.4% for Extensively drug resistant TB (XDR) treatment. Among these cases, it was found that the median time from diagnosis to treatment initiation was 6 days (IQR:2-15.8). The median time was 5 days (IQR:2.0-13.3) among STR, 6 days (IQR:3.0-15.0) among LTR, 30 days (IQR:5.5-66.8) among Pre-XDR and 4 days (IQR:2.5-9.0) among XDR TB cases. The overall treatment delay (>7 days after diagnosis) was observed in 42.4% of the patients, among which, cases enrolled under Pre-XDR contributed substantially to treatment delay (72.0%), followed by LTR (43.6%), STR (39.1%) and XDR (33.3%). Conclusion: Timely diagnosis and prompt treatment initiation remain fundamental focus of the National TB program. The findings of the study, however suggest gaps in timeliness of treatment initiation for the drug-resistant TB patients, which could bring adverse treatment outcomes. Moreover, there is an alarming delay in second line treatment initiation for the Pre-XDR TB patients. Therefore, this study generates evidence to identify existing gaps in treatment initiation and highlights need for formulating specific policies and intervention in creating effective linkage between the RR TB diagnosis and enrollment on second line TB treatment with intensified efforts from health providers for follow-ups and expansion of more decentralized, adequate, and accessible diagnostic and treatment services for DR-TB, especially Pre-XDR TB cases, due to the observed long treatment delays.

Keywords: drug-resistant, tuberculosis, treatment initiation, Nepal, treatment delay

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