Search results for: central nervous system tuberculosis

Authors: Minna Chang

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Introduction: M. pneumoniae is a respiratory pathogen, which commonly causes upper and lower respiratory infections. It primarily affects children and young adults. Respiratory symptoms are well recognized, but extrapulmonary involvement is also common. Other systems that have been implicated in the disease include: skin, mucus membranes, central, peripheral nervous systems, cardiovascular, haematological, renal, and musculoskeletal systems. Here, we report a case of an otherwise healthy, young female with M. pneumonia, who presented with right upper quadrant abdominal pain. Case presentation: a healthy 25-year-old female was referred to A&E by her general practitioner, after presenting with fever, malaise, and right upper quadrant pain. M. pneumoniae was confirmed retrospectively by serology. The patient made a full recovery after a six-day course of doxycycline 100mg. Conclusion: M. pneumonia is a well-established cause of respiratory infections in children and young adults. Febrile illness with multisystem involvement, even in the absence of respiratory symptoms, should raise suspicion of M. pneumoniae infection in healthy, young adults. Our case illustrates the multi-system involvement of M. pneumoniae, which was initially missed, due to paucity of respiratory symptoms at presentation.

Keywords: infectious diseases, mycoplasma pneumoniae, respiratory infections, extra-pulmonary manifestations

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Authors: Ghoul Rachid Brahim

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Introduction: Tuberculous spondylodiscitis is an infection of the spine by Mycobacterium tuberculosis. Tuberculous spondylodiscitis still remains a topical disease in developing countries and continues to pose a public health problem in endemic countries. Materials and methods: Clinical case: This is a 12-year-old child followed in pediatrics for weight loss and progressively worsening low back pain. The neurological examination found an irritative pyramidal syndrome in both lower limbs with a severe lumbar spinal syndrome. The radiological assessment: (Rx of the spine supplemented by CT and MRI) shows L1L2 spondylodiscitis. Treatment: The child is put on anti-tuberculosis treatment, and the spine is restrained with a corset. Control MRI shows a worsening of the dorsal kyphosis with a backward movement of the posterior wall and spinal cord compression. The child is operated on via the posterior approach (the operative procedure consists of an L1 laminectomy and D11 L3 osteosynthesis). Results: Spinal cord décompression and stabilization of the spine. Conclusion: Tuberculous spondylodiscitis in children remains a rare, aggressive, and progressive condition. The prognosis depends on the diagnosis's precocity and the therapeutic management quality.

Keywords: tuberculous spondylodiscitis, mycobacterium tuberculosis, laminectomy, MRI

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Authors: Fabio Marson, Revital Naor-Ziv, Patrizio Paoletti, Joseph Glicksohn, Filippo Carducci, Tal Dotan Ben-Soussan

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According to embodied cognition theories, higher-order cognitive functions and complex behaviors seems to be affected by bodily states. For example, the polyvagal theory suggests that the human autonomic nervous system evolved to support social interactions. Accordingly, integration and perception of information related to the physiological state arising from the peripherical nervous system (i.e., interoception) play a role in the regulation of social interaction by modulating emotional responses and prosocial behaviors. Moreover, recent studies showed that interoception is involved in the representations of conceptual knowledge, suggesting that the bodily information carried by the interoceptive system provides a perceptual basis for the embodiment of abstract concepts, especially those related to social and emotional domains. However, to the best of our knowledge, no studies explored the relationship between interoception, prosocial behaviors, and conceptual representations. Considering the privileged position of interoception in mediating higher-order cognition and social interaction, we designed a cross-cultural study to explore the relationship between interoception, the sensitivity of bodily functions, and empathy. We recruited Italian, English, and Hebrew participants, and we asked them to fill in a questionnaire about empathy (Empathy Quotient), a questionnaire about bodily perception (Body Perception Questionnaire), and to rate different concrete and abstract concepts for the extent such concepts can be experienced through vision, hearing, taste, smell, touch, and interoception. We observed that in all languages, interoception ratings for abstract concepts were greater than for concrete concepts. Importantly, interoception ratings for abstract concepts were positively correlated with empathy and sensitivity of bodily functions. Our results suggest that participants with higher empathy and sensitivity of bodily functions show also a greater embodiment of abstract concepts in interoception, providing further evidence for the importance of the interoceptive system in regulating prosocial behaviors and integrating conceptual representations.

Keywords: conceptual representations, embodiment, empathy, empathy quotient, interoception, prosocial behaviors

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Authors: Olga Andrianova, Lazar Jeifets

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The security issue has always been one of the most sensitive and significant in Latin American context, especially focused on Central American region. Despite the fact that the time of the civil wars has ended, violence, delinquency, insecurity, discrimination still exist and keep relevance in the 21st century. This article is dedicated to consider this kind of problems, to find out the main causes and to propose solution approaches.

Keywords: Central America, insecurity, instability, post-war countries, violence

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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: Olga Andrianova, Lazar Jeifets

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The security issue has always been one of the most sensitive and significant in Latin American context, especially focused on Central American region. Despite the fact that the time of the civil wars has ended, violence, delinquency, insecurity, discrimination still exist and keep relevance in the 21st century. This article is dedicated to consider this kind of problems, to find out the main causes and to propose solution approaches.

Keywords: Central America, insecurity, instability, violence

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Authors: Ranjeet Kumar, Pravin Suryakantrao Deshmukh, Sonal Sharma, Basudev Banerjee

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With the tremendous increase in exposure to radiofrequency microwaves emitted by mobile phones, globally public awareness has grown with regard to the potential health hazards of microwaves on the nervous system in the brain. India alone has more than one billion mobile users out of 4.3 billion globally. Our studies have suggested that radio frequency able to affect neuronal alterations in the brain, and hence, affecting cognitive behaviour. However, adverse effect of low-intensity microwave exposure with endoplasmic reticulum stress and autophagy has not been evaluated yet. In this study, we explore whether low-intensity microwave induces endoplasmic reticulum stress and autophagy with varying frequency and time duration in Wistar rat. Ninety-six male Wistar rat were divided into 12 groups of 8 rats each. We studied at 900 MHz, 1800 MHz, and 2450 MHz frequency with reference to sham-exposed group. At the end of the exposure, the rats were sacrificed to collect brain tissue and expression of CHOP, ATF-4, XBP-1, Bcl-2, Bax, LC3 and Atg-4 gene was analysed by real-time PCR. Significant fold change (p < 0.05) of gene expression was found in all groups of 1800 MHz and 2450 MHz exposure group in comparison to sham exposure group. In conclusion, the microwave exposure able to induce ER stress and modulate autophagy. ER (endoplasmic reticulum) stress and autophagy vary with increasing frequency as well as the duration of exposure. Our results suggested that microwave exposure is harmful to neuronal health as it induces ER stress and hampers autophagy in neuron cells and thereby increasing the neuron degeneration which impairs cognitive behaviour of experimental animals.

Keywords: autophagy, ER stress, microwave, nervous system, rat

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Authors: Emílie Kučerová, Tereza Veverková, Marina Morozovová, Eva Kudová, Jitka Viktorová

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The blood-brain barrier (BBB) is a key element regulating the transport of substances between the blood and the central nervous system (CNS). The BBB protects the CNS from potentially harmful substances and maintains a suitable environment for nervous activity in the CNS, but at the same time, it represents a significant obstacle to the entry of drugs into the CNS. Pharmacoresistant epilepsy is a form of epilepsy that cannot be suppressed using two (or more) appropriately chosen antiepileptic drugs. In many cases, pharmacoresistant epilepsy is characterized by an increased concentration of efflux pumps on the luminal sides of the endothelial cells that form the BBB and an increased number of drug-metabolizing enzymes in the BBB cells, thereby preventing the effective transport of antiepileptic drugs into the CNS. Currently, a number of scientific groups are focusing on the preparation and improvement of BBB models in vitro in order to study cell interactions or transport mechanisms. However, in pathological conditions such as pharmacoresistant epilepsy, there are changes in BBB structure, and current BBB models are insufficient for related research. Our goal is to develop a suitable BBB model for pharmacoresistant epilepsy in vitro and use it to test the transfer of potential antiepileptic drugs. This model is created by co-culturing immortalized human cerebral microvascular endothelial cells, human vascular pericytes and immortalized human astrocytes. The BBB in vitro is cultivated in the form of a 2D transwell model and the integrity of the barrier is verified by measuring transendothelial electrical resistance (TEER). From the current results, a contact cell arrangement with the cultivation of endothelial cells on the upper side of the insert and the co-cultivation of astrocytes and pericytes on the lower side of the insert is selected as the most promising for BBB model cultivation. The pharmacoresistance of the BBB model is achieved by long-term cultivation of endothelial cells in an increasing concentration of selected antiepileptic drugs, which should lead to increased production of efflux pumps and drug-metabolizing enzymes. The pharmacoresistant BBB model in vitro will be further used for the screening of substances that could act both as antiepileptics and at the same time as inhibitors of efflux pumps in endothelial cells. This project was supported by the Technology Agency of the Czech Republic (TACR), Personalized Medicine: Translational research towards biomedical applications, No. TN02000109 and by the Academy of Sciences of the Czech Republic (AS CR) – grant RVO 61388963.

Keywords: antiepileptic drugs, blood-brain barrier, efflux transporters, pharmacoresistance

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Authors: Guyue Zhu, Liangping Hong

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Chinese overall urban design faces a large number of problems such as the neglect of urban characteristics, generalization of content, and difficulty in implementation. Focusing on these issues, this paper proposes the main points of shaping urban characteristics in overall urban design: focuses on core problems in city function and scale, landscape pattern, historical culture, social resources and modern city style and digs the urban characteristic genes. Then, we put forward “core problem location and characteristic gene enhancement” as a kind of overall urban design technical method. Firstly, based on the main problems in urban space as a whole, for the operability goal, the method extracts the key genes and integrates into the multi-dimension system in a targeted manner. Secondly, hierarchical management and guidance system is established which may be in line with administrative management. Finally, by converting the results, action plan is drawn up that can be dynamically implemented. Based on the above idea and method, a practical exploration has been performed in the case of Xiangyang central city.

Keywords: city characteristics, overall urban design, planning implementation, Xiangyang central city

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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: Sima Aznavi, Poria Fajri, Hanif Livani

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Smart homes are small energy systems which may be equipped with renewable energy sources, storage devices, and loads. Energy management strategy plays a main role in the efficient operation of smart homes. Effective energy scheduling of the renewable energy sources and storage devices guarantees efficient energy management in households while reducing the energy imports from the grid. Nevertheless, despite such strategies, independently day ahead energy schedules for multiple households can cause undesired effects such as high power exchange with the grid at certain times of the day. Therefore, the interactions between multiple smart home day ahead energy projections is a challenging issue in a smart grid system and if not managed appropriately, the imported energy from the power network can impose additional burden on the distribution grid. In this paper, a central energy management strategy for a network consisting of multiple households each equipped with renewable energy sources, storage devices, and Plug-in Electric Vehicles (PEV) is proposed. The decision-making strategy alongside the smart home energy management system, minimizes the energy purchase cost of the end users, while at the same time reducing the stress on the utility grid. In this approach, the smart home energy management system determines different operating scenarios based on the forecasted household daily load and the components connected to the household with the objective of minimizing the end user overall cost. Then, selected projections for each household that are within the same cost range are sent to the central decision-making system. The central controller then organizes the schedules to reduce the overall peak to average ratio of the total imported energy from the grid. To validate this approach simulations are carried out for a network of five smart homes with different load requirements and the results confirm that by applying the proposed central energy management strategy, the overall power demand from the grid can be significantly flattened. This is an effective approach to alleviate the stress on the network by distributing its energy to a network of multiple households over a 24- hour period.

Keywords: energy management, renewable energy sources, smart grid, smart home

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Authors: Lok Raj Joshi, Naveen Prakash Shah, Sharad Kumar Sharma, I. Ratna Bhattarai, Rajendra Basnet, Deepak Dahal, Bahagwan Maharjan, Seraphine Kaminsa

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Context: Tuberculosis (TB) is a significant health issue in Nepal, a country with a high burden of the disease. Despite efforts to control TB, there is still a gap in the notification of TB cases, which hinders effective control and treatment. This paper aims to address this notification gap and proposes strategies to improve TB control in Nepal. Research Aim: The aim of this research is to understand and address the tuberculosis notification gap in Nepal. The focus is on enhancing the healthcare system, involving the private sector and communities, raising awareness, and addressing social determinants to achieve sustainable TB control. Methodology: The research methodology involved a review of existing epidemiological data and research studies related to TB in Nepal. Additionally, consultation with an expert group from the TB control program in Nepal provided insights into the current state of TB control and challenges in addressing the notification gap. Findings: The findings reveal that only 55% of TB cases were reported in 2022, indicating a significant notification gap. Of the reported cases, only 32% and 19% were referred by the private sector and community, respectively. Furthermore, 20% of diagnosed cases were not treated in the initial phase. The estimated number of cases of multidrug-resistant TB (MDR TB) was 2,800, suggesting a low diagnosis rate. Among the diagnosed MDR TB cases, only 60% were receiving treatment. Additionally, it was observed that 20% of diagnosed MDR TB cases were from India and not enrolling in TB treatment in Nepal, indicating a high rate of defaulters. Theoretical Importance: The study highlights the importance of adopting a holistic strategy to address the notification gap in TB cases in Nepal. It emphasizes the need to enhance healthcare infrastructure, raise awareness, involve the private sector and local communities, establish effective methods to trace initial defaulters, implement TB interventions in border regions, and mitigate the social stigma associated with the disease. Data Collection and Analysis Procedures: Data for this study was collected through a review of existing epidemiological data and research studies. The data were then analyzed to identify patterns, trends, and gaps in TB case notification in Nepal.

Keywords: TB, tuberculosis, private sector, community, migrants, nepal

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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: Pritika Ramharack, Mahmoud E. S. Soliman

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The re-emerging Zika virus is an arthropod-borne virus that has been described to have explosive potential as a worldwide pandemic. The initial transmission of the virus was through a mosquito vector, however, evolving modes of transmission has allowed the spread of the disease over continents. The virus already been linked to irreversible chronic central nervous system (CNS) conditions. The concerns of the scientific and clinical community are the consequences of Zika viral mutations, thus suggesting the urgent need for viral inhibitors. There have been large strides in vaccine development against the virus but there are still no FDA-approved drugs available. Rapid rational drug design and discovery research is fundamental in the production of potent inhibitors against the virus that will not just mask the virus, but destroy it completely. In silico drug design allows for this prompt screening of potential leads, thus decreasing the consumption of precious time and resources. This study demonstrates an optimized and proven screening technique in the discovery of two potential small molecule inhibitors of Zika virus Methyltransferase and RNA-dependent RNA polymerase. This in silico “per-residue energy decomposition pharmacophore” virtual screening approach will be critical in aiding scientists in the discovery of not only effective inhibitors of Zika viral targets, but also a wide range of anti-viral agents.

Keywords: NS5 protein inhibitors, per-residue decomposition, pharmacophore model, virtual screening, Zika virus

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Authors: Kaouther Selmi, Alaeddine Sridi, Mohamed Bouallegue, Kais Bouallegue

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Neurons are the fundamental units of the brain and the nervous system. The variable structure model of neurons consists of a system of differential equations with various parameters. By optimizing these parameters, we can create a unique model that describes the dynamic behavior of a single neuron. We introduce a neural network based on neurons with multiple dendrites employing an activation function with a variable structure. In this paper, we present a model for heart behavior. Finally, we showcase our successful simulation of the heart's ECG diagram using our Variable Structure Neuron Model (VSMN). This result could provide valuable insights into cardiology.

Keywords: neural networks, neuron, dendrites, heart behavior, ECG

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Authors: Atefeh Abedini, Fatemeh Razavi, Mihan Pourabdollah Toutkaboni, Hossein Mehravaran, Arda Kiani

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In countries with the highest prevalence of tuberculosis, such as Iran, the differentiation of malignant tumors from non-malignant is very important. In this study, which was conducted for the first time among the Iranian population, the utility of the ultrasonographic morphological characteristics in patients undergoing EBUS was used to distinguish the non-malignant versus malignant lymph nodes. The morphological characteristics of lymph nodes, which consist of size, shape, vascular pattern, echogenicity, margin, coagulation necrosis sign, calcification, and central hilar structure, were obtained during Endobronchial Ultrasound-Guided Trans-Bronchial Needle Aspiration and were compared with the final pathology results. During this study period, a total of 253 lymph nodes were evaluated in 93 cases. Round shape, non-hilar vascular pattern, heterogeneous echogenicity, hyperechogenicity, distinct margin, and the presence of necrosis sign were significantly higher in malignant nodes. On the other hand, the presence of calcification and also central hilar structure were significantly higher in the benign nodes (p-value ˂ 0.05). Multivariate logistic regression showed that size>1 cm, heterogeneous echogenicity, hyperechogenicity, the presence of necrosis signs and, the absence of central hilar structure are independent predictive factors for malignancy. The accuracy of each of the aforementioned factors is 42.29 %, 71.54 %, 71.90 %, 73.51 %, and 65.61 %, respectively. Of 74 malignant lymph nodes, 100% had at least one of these independent factors. According to our results, the morphological characteristics of lymph nodes based on Endobronchial Ultrasound-Guided Trans-Bronchial Needle Aspiration can play a role in the prediction of malignancy.

Keywords: EBUS-TBNA, malignancy, nodal characteristics, pathology

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Authors: Rithika Sriram, Kiran M. Bhojwani

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Introduction : Tuberculosis of the head and neck has proved to be a diagnostic challenge for otorhinolarynologists around the world. These lesions are often misdiagnosed as cancer. So in order to contribute to a better understanding of these lesions, we have conducted our study among patients affected by TB in the head and neck region with the objective of assessing the various manifestations, presentations, diagnostic techniques, risk factors such as smoking and alcohol consumption, coexisting illnesses and treatment modalities. Materials and Methods: This was a retrospective study conducted over a three year period (2012-2014) in 2 hospitals affliated to Kasturba Medical College in Mangalore, South India. A semi structured proforma was used to capture information from the medical records pertaining to the various objectives of the study such as clinical features and history of smoking. Data was analysed using SPSS version 16.0 and results obtained were depicted as percentages. Chi square test was used to find association between the variables and p<0.05 was considered statistically significant. Results: 104 patients were found to have TB of the head and neck and among them,the most common manifestation was found to be Tubercular Lymphadenitis (86.53%), followed by laryngeal TB (4.8%), submandibular gland TB (3.8%), deep neck space abscess(3.8%) and adenotonsillar TB. FNAC was found to be the gold standard for the diagnosis of TB disease of the lymph node.26% of the patients had coexisting HIV infection and 16.3% of the patients had associated pulmonary TB. More than 20% of the patients were smokers. Most patients were treated using ATT. Conclusion: Tuberculosis affecting regions of head and neck is no longer uncommon. Sufficient knowledge and appropriate diagnostic means is required while dealing with these lesions and must be included in the differential diagnosis of pathological lesions of head and neck.

Keywords: FNAC, Mangalore, smoking, tuberculosis

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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: Joanna Cabaj, Sylwia Baluta, Karol Malecha

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Catecholamines are vital neurotransmitters that mediate a variety of central nervous system functions, such as motor control, cognition, emotion, memory processing, and endocrine modulation. Dysfunctions in catecholamine neurotransmission are induced in some neurologic and neuropsychiatric diseases. Changeable neurotransmitters level in biological fluids can be a marker of several neurological disorders. Because of its significance in analytical techniques and diagnostics, sensitive and selective detection of neurotransmitters is increasingly attracting a lot of attention in different areas of bio-analysis or biomedical research. Recently, optical techniques for the detection of catecholamines have attracted interests due to their reasonable cost, convenient control, as well as maneuverability in biological environments. Nevertheless, with the observed need for a sensitive and selective catecholamines sensor, the development of a convenient method for this neurotransmitter is still at its basic level. The manipulation of nanostructured materials in conjunction with biological molecules has led to the development of a new class of hybrid-modified enzymatic sensors in which both enhancement of charge transport and biological activity preservation may be obtained. Immobilization of biomaterials on electrode surfaces is the crucial step in fabricating electrochemical as well as optical biosensors and bioelectronic devices. Continuing systematic investigation in manufacturing of enzyme–conducting sensitive systems, here is presented a convenient fluorescence as well as electrochemical sensing strategy for catecholamines detection.

Keywords: biosensors, catecholamines, fluorescence, enzymes

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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: A. J. S. P. Nileema, S. Kulatunga , S. H. Palihawadana

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Computer aided detection (CAD) system was developed for the diagnosis of pulmonary tuberculosis using digital chest X-rays with MATLAB image processing techniques using a statistical approach. The study comprised of 200 digital chest radiographs collected from the National Hospital for Respiratory Diseases - Welisara, Sri Lanka. Pre-processing was done to remove identification details. Lung fields were segmented and then divided into four quadrants; right upper quadrant, left upper quadrant, right lower quadrant, and left lower quadrant using the image processing techniques in MATLAB. Contrast, correlation, homogeneity, energy, entropy, and maximum probability texture features were extracted using the gray level co-occurrence matrix method. Descriptive statistics and normal distribution analysis were performed using SPSS. Depending on the radiologists’ interpretation, chest radiographs were classified manually into PTB - positive (PTBP) and PTB - negative (PTBN) classes. Features with standard normal distribution were analyzed using an independent sample T-test for PTBP and PTBN chest radiographs. Among the six features tested, contrast, correlation, energy, entropy, and maximum probability features showed a statistically significant difference between the two classes at 95% confidence interval; therefore, could be used in the classification of chest radiograph for PTB diagnosis. With the resulting value ranges of the five texture features with normal distribution, a classification algorithm was then defined to recognize and classify the quadrant images; if the texture feature values of the quadrant image being tested falls within the defined region, it will be identified as a PTBP – abnormal quadrant and will be labeled as ‘Abnormal’ in red color with its border being highlighted in red color whereas if the texture feature values of the quadrant image being tested falls outside of the defined value range, it will be identified as PTBN–normal and labeled as ‘Normal’ in blue color but there will be no changes to the image outline. The developed classification algorithm has shown a high sensitivity of 92% which makes it an efficient CAD system and with a modest specificity of 70%.

Keywords: chest radiographs, computer aided detection, image processing, pulmonary tuberculosis

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Authors: Surendra Mund

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At the beginning, the physical entity force was defined mathematically by Sir Isaac Newton in his Principia Mathematica as F ⃗=(dp ⃗)/dt in form of his second law of motion. Newton also defines his Universal law of Gravitational force exist in same outstanding book, but at the end of 20th century and beginning of 21st century, we have tried a lot to specify and unify four or five Fundamental forces or Interaction exist in universe, but we failed every time. Usually, Gravity creates problems in this unification every single time, but in my previous papers and presentations, I defined and derived Field and force equations for Gravitational like Interactions for each and every kind of central systems. This force is named as Variational Force by me, and this force is generated by variation in the scalar field density around the body. In this particular paper, at first, I am specifying which type of Interactions are Fundamental in Universal sense (or in all type of central systems or bodies predicted by my N-time Inflationary Model of Universe) and then unify them in Universal framework (defined and derived by me as Universal Mechanics in a separate paper) as well. This will also be valid in Universal dynamical sense which includes inflations and deflations of universe, central system relativity, Universal relativity, ϕ-ψ transformation and transformation of spin, physical perception principle, Generalized Fundamental Dynamical Law and many other important Generalized Principles of Generalized Quantum Mechanics (GQM) and Central System Theory (CST). So, In this article, at first, I am Generalizing some Fundamental Principles, and then Unifying Variational Forces (General form of Gravitation like Interactions) and Flow Generated Force (General form of EM like Interactions), and then Unify all Fundamental Forces by specifying Weak and Strong Interactions in form of more basic terms - Variational, Flow Generated and Transformational Interactions.

Keywords: Central System Force, Disturbance Force, Flow Generated Forces, Generalized Nuclear Force, Generalized Weak Interactions, Generalized EM-Like Interactions, Imbalance Force, Spin Generated Forces, Transformation Generated Force, Unified Force, Universal Mechanics, Uniform And Non-Uniform Variational Interactions, Variational Interactions

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Authors: M. F. Abreu, A. I. Aguiar, R. Gaio, R. Duarte

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Background: Prison establishments constitute high-risk environments for the transmission and spread of tuberculosis (TB), given their epidemiological context and the difficulty of implementing preventive and control measures. Guidelines for control and prevention of tuberculosis in prisons have been described as incomplete and heterogeneous internationally, due to several identified obstacles, for example scarcity of human resources and funding of prisoner health services. In Portugal, a protocol was created in 2014 with the aim to define and standardize procedures of detection and prevention of tuberculosis within prisons. Objective: The main objective of this study was to identify and describe barriers to tuberculosis detection in prisons of Porto and Lisbon districts in Portugal. Methods: A cross-sectional study was conducted from 2ⁿᵈ January 2018 till 30ᵗʰ June 2018. Semi-structured questionnaires were applied to health care professionals working in the prisons of the districts of Porto (n=6) and Lisbon (n=8). As inclusion criteria we considered having work experience in the area of tuberculosis (either in diagnosis, treatment, or follow up). The questionnaires were self-administered, in paper format. Descriptive analyses of the questionnaire variables were made using frequencies and median. Afterwards, a hierarchical agglomerative clusters analysis was performed. After obtaining the clusters, the chi-square test was applied to study the association between the variables collected and the clusters. The level of significance considered was 0.05. Results: From the total of 186 health professionals, 139 met the criteria of inclusion and 82 health professionals were interviewed (62,2% of participation). Most were female, nurses, with a median age of 34 years, with term employment contract. From the cluster analysis, two groups were identified with different characteristics and behaviors for the procedures of this protocol. Statistically significant results were found in: elements of cluster 1 (78% of the total participants) work in prisons for a longer time (p=0.003), 45,3% work > 4 years while 50% of the elements of cluster 2 work for less than a year, and more frequently answered they know and apply the procedures of the protocol (p=0.000). Both clusters answered frequently the need of having theoretical-practical training for TB (p=0.000), especially in the areas of diagnosis, treatment and prevention and that there is scarcity of funding to prisoner health services (p=0.000). Regarding procedures for TB screening (periodic and contact screening) and procedures for transferring a prisoner with this disease, cluster 1 also answered more frequently to perform them (p=0.000). They also referred that the material/equipment for TB screening is accessible and available (p=0.000). From this clusters we identified as barriers scarcity of human resources, the need to theoretical-practical training for tuberculosis, inexperience in working in health services prisons and limited knowledge of protocol procedures. Conclusions: The barriers found in this study are the same described internationally. This protocol is mostly being applied in portuguese prisons. The study also showed the need to invest in human and material resources. This investigation bridged gaps in knowledge that could help prison health services optimize the care provided for early detection and adherence of prisoners to treatment of tuberculosis.

Keywords: barriers, health care professionals, prisons, protocol, tuberculosis

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Authors: Y. Melis, E. Apicella, E. Dozio, L. Mendolicchio

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Introduction: Feeding and Eating Disorders (FED) represent the psychiatric pathology with the highest mortality rate and one of the major disorders with the highest psychiatric and clinical comorbidity. The vagus nerve represents one of the main components of the sympathetic and parasympathetic nervous system and is involved in important neurophysiological functions. In FED, there is a spectrum of symptoms which with TaVNS (Transcutaneous Auricular Vagus Nerve Stimulation) therapy, is possible to have a therapeutic efficacy. Materials and Methods: Sample subjects are composed of 15 female subjects aged > 18 ± 51. Admitted to a psychiatry community having been diagnosed according to DSM-5: anorexia nervosa (AN) (N= 9), bulimia nervosa (BN) (N= 5), binge eating disorder (BED) (N= 1). The protocol included 9 weeks of Ta-VNS stimulation at a frequency of 1.5-3.5 mA for 4 hours per day. The variables detected are the following: Heart Rate Variability (HRV), Hamilton Depression Rating Scale (HAMD-HDRS-17), Body Mass Index (BMI), Beck Anxiety Index (BAI). Results: Data analysis showed statistically significant differences between recording times (p > 0.05) in HAM-D (t0 = 18.28 ± 5.31; t4 = 9.14 ± 7.15), in BAI (t0 = 24.7 ± 10.99; t4 = 13.8 ± 7.0). The reported values show how during (T0-T4) the treatment there is a decay of the degree in the depressive state, in the state of anxiety, and an improvement in the value of BMI. In particular, the BMI in the AN-BN sub-sample had a minimum gain of 5% and a maximum of 11%. The analysis of HRV did not show a clear change among subjects, thus confirming the discordance of the activity of the sympathetic and parasympathetic nervous system in FED. Conclusions: Although the sample does not possess a relevant value to determine long-term efficacy of Ta-VNS or on a larger population, this study reports how the application of neuro-stimulation in FED may become a further approach therapeutic. Indeed, substantial improvements are highlighted in the results and confirmed hypotheses proposed by the study.

Keywords: feeding and eating disorders, neurostimulation, anxiety disorders, depression

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Authors: Francesco Angelucci, Katerina Veverova, Alžbeta Katonová, Lydia Piendel, Martin Vyhnalek, Jakub Hort

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Alzheimer's disease (AD) is a central nervous system (CNS) disease characterized by loss of memory, cognitive functions and neurodegeneration. Plasmin is an enzyme degrading many plasma proteins. In the CNS, plasmin may reduce the accumulation of A, and have other actions relevant to AD pathophysiology. Brain plasmin synthesis is regulated by two enzymes: one activating, the tissue plasminogen activator (tPA), and the other inhibiting, the plasminogen activator inhibitor-1 (PAI-1). We investigated whether tPA and PAI-1 serum levels in AD and amnestic mild cognitive impairment (aMCI) patients are altered compared to cognitively healthy controls. Moreover, we examined the PAI-1/tPA ratio in these patient groups. 40 AD, 40 aMCI and 10 healthy controls were recruited. Venous blood was collected and PAI-1 and tPA serum concentrations were quantified by sandwich ELISAs. The results showed that PAI-1 levels increased in AD and aMCI patients. This increase negatively correlated with cognitive deficit measured by MMSE. Similarly, the ratio between tPA and PAI-1 gradually increases in aMCI and AD patients. This study demonstrates that AD and aMCI patients have altered PAI-1 serum levels and PAI-1/tPA ratio. Since these enzymes are CNS regulators of plasmin, PAI-1 serum levels could be a marker reflecting a cognitive decline in AD.

Keywords: Alzheimer disease, amnestic mild cognitive impairment, plasmin, tissue-type plasminogen activator

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

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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: Ritika Jain, Rajnish Kumar

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The Department of Public Enterprises had made submissions of Self Evaluation Reports, for the purpose of corporate governance, mandatory for all central government owned enterprises. Despite this, an alarming 40% of the enterprises did not do so. This study examines the impact of external policy tools and internal firm-specific factors on corporate governance of central public sector enterprises (CPSEs). We use a dataset of all manufacturing and non-financial services owned by the central government of India for the year 2010-11. Using probit, ordered logit and Heckman’s sample selection models, the study finds that the probability and quality of corporate governance is positively influenced by the CPSE getting into a Memorandum of Understanding (MoU) with the central government of India, and hence, enjoying more autonomy in terms of day to day operations. Besides these, internal factors, including bigger size and lower debt size contribute significantly to better corporate governance.

Keywords: corporate governance, central public sector enterprises (CPSEs), sample selection, Memorandum of Understanding (MoU), ordered logit, disinvestment

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