Search results for: tuberculosis burden in India

Authors: Sudipto Jana

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Background and significance of the study: Banking industry performs as a catalyst for industrial growth and agricultural growth, however, as well involves the existence and welfare of the citizens. The banking system in India was described by unmatched growth and the recreation of bunch making in the pre-liberalization era. At the time of financial sector reforms Reserve Bank of India issued a regulatory norm concerning capital adequacy, income recognition, asset classification and provisioning that have increasingly precede meeting by means of the international paramount performs. Bank management ceaselessly manages the triumph, effectiveness, productivity and performance of the bank as good performance, high productivity and efficiency authorizes the triumph of the bank management targets as well as aims of bank. In a comparable move toward performance of any economy depends upon the expediency and effectiveness of its financial system of nation establishes its economic growth indicators. Profitability and productivity are the most important relevant parameters of any banking group. Keeping in view of this, this study examines the profitability and productivity performance of the selected public sector banks in India. Methodology: This study is based on secondary data obtained from Reserve Bank of India database for the periods between 2006 and 2015. This study purposively selects four types of commercial banks, namely, State Bank of India, United Bank of India, Punjab National Bank and Allahabad Bank. In order to analyze the performance with relation to profitability and productivity, productivity performance indicators in terms of capital adequacy ratio, burden ratio, business per employee, spread per employee and advances per employee and profitability performance indicators in terms of return on assets, return on equity, return on advances and return on branch have been considered. In the course of analysis, descriptive statistics, correlation statistics and multiple regression have been used. Major findings: Descriptive statistics indicate that productivity performance of State Bank of India is very satisfactory than other public sector banks in India. But management of productivity is unsatisfactory in case of all the public sector banks under study. Correlation statistics point out that profitability of the public sector banks are strongly positively related with productivity performance in case of all the public sector banks under study. Multiple regression test results show that when profitability increases profit per employee increases and net non-performing assets decreases. Concluding statements: Productivity and profitability performance of United Bank of India, Allahabad Bank and Punjab National Bank are unsatisfactory due to poor management of asset quality as well as management efficiency. It needs government’s interference so that profitability and productivity performance are increased in the near future.

Keywords: India, productivity, profitability, public sector banks

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Authors: Desiree Vandenberghe, Johan Albrecht

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Non-communicable diseases (NCDs) are responsible for the vast majority of deaths in the European Union (EU) and represent a large share of total health care spending. A future increase in this health and financial burden is likely to be driven by population ageing, lifestyle changes and technological advances in medicine. Without adequate prevention measures, this burden can severely threaten population health and economic development. To tackle this challenge, a correct assessment of the current burden of NCDs is required, as well as a projection of potential increases of this burden. The contribution of this paper is to offer perspective on the evolution of the NCD burden towards the future and to give an indication of the potential of prevention policy. A Non-Homogenous, Semi-Markov model for the EU was constructed, which allowed for a projection of the cost burden for the four main NCDs (cancer, cardiovascular disease, chronic respiratory disease and diabetes mellitus) towards 2030 and 2050. This simulation is done based on multiple baseline scenarios that vary in demand and supply factors such as health status, population structure, and technological advances. Finally, in order to assess the potential of preventive measures to curb the cost explosion of NCDs, a simulation is executed which includes increased efforts for preventive health care measures. According to the Markov model, by 2030 and 2050, total costs (direct and indirect costs) in the EU could increase by 30.1% and 44.1% respectively, compared to 2015 levels. An ambitious prevention policy framework for NCDs will be required if the EU wants to meet this challenge of rising costs. To conclude, significant cost increases due to Non-Communicable Diseases are likely to occur due to demographic and lifestyle changes. Nevertheless, an ambitious prevention program throughout the EU can aid in making this cost burden manageable for future generations.

Keywords: non-communicable diseases, preventive health care, health policy, Markov model, scenario analysis

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Authors: Smita Singh

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Through the constructivist perspective, this paper explores the transformation of India’s nuclear identity from an irresponsible nuclear weapon power to a ‘de-facto nuclear power’ in the emerging international nuclear order From a nuclear abstainer to a bystander and finally as a ‘de facto nuclear weapon state’, India has put forth its case as a unique and exceptional nuclear power as opposed to Iran, Iraq and North Korea with similar nuclear ambitions, who have been snubbed as ‘rogue states’ by the international community. This paper investigates the reasons behind international community’s gradual acceptance of India’s nuclear weapons capabilities and nuclear identity after the Indo-U.S. Nuclear Deal. In this paper, the central concept of analysis is the inter-subjective nature of identity in the nuclear arena. India’s nuclear behaviour has been discursively constituted by India through evolving images of the ‘self’ and the ‘other.’ India’s sudden heightened global status is not solely the consequence of its 1998 nuclear tests but a calibrated projection as a responsible stakeholder in other spheres such as economic potential, market prospects, democratic credentials and so on. By examining India’s nuclear discourse this paper contends that India has used its material and discursive power in presenting a n striking image as a responsible nuclear weapon power (though not yet a legal nuclear weapon state as per the NPT). By historicising India’s nuclear trajectory through an inter-subjective analysis of identities, this paper moves a step ahead in providing a theoretical interpretation of state actions and nuclear identity construction.

Keywords: nuclear identity, India, constructivism, international stakeholder

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Authors: N. Sathish Gowda

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A constitution without fundamental rights will become zero. The very object of constitution of three organs viz, legislature, executive and judiciary under the constitution of India is to protect, preserve and promote fundamental rights guaranteed under part-III. In India, along with express fundamental rights, Supreme Court has also recognized implied fundamental rights. But, unfortunately State has not been implementing these implied fundamental rights. In this regard, this research paper discusses the catalogue of implied fundamental rights evolved by the judiciary in interpreting Article 21 of the Constitution of India and seeks to examine the effects and applicability of these rights in India.

Keywords: fundamental rights, nuances of Article 21, express fundamental rights, implied fundamental rights, procedure established by law

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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: 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: Yadav R. K., Baral S.

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

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

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Authors: J. K. D. M. P. Madara, R. B. L. Dharmawickreme, Linu John, Ivee Boiss

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Flemingia vestita, commonly known as ‘Sohphlang’ is an important medicinal plant found in the North-Eastern region of India, which is traditionally recognized for its anthelmintic properties. This study was aimed to evaluate the phytochemical constituents and antibacterial activity of the tuber skin extracts of the plant species. Methanol, acetone, and water were used to obtain the solvent extractions of the skin peel extracts. Concentrated extracts of skin peel were tested using previously established qualitative phytochemical assays. The antibacterial efficacy of methanol tuber skin extract was tested against Gram-negative and positive microorganisms, namely, Klebsiella pneumonia, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Mycobacterium tuberculosis strains. Agar well diffusion method was employed to determine the zone of inhibition of the plant extracts. Obtained data were statistically analyzed. Methanol extracts of Flemingia vestita were found to be effective against Bacillus subtilis and Mycobacterium tuberculosis at concentrations of 0.5 mg/ml. The reported zone of inhibition for the two strains was 13.3mm ± 0.57 and 16.3mm ± 4.9, respectively. However Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli were resistant to the plant extracts with no zone of inhibition. Alkaloids, glycosides, and phenols were found to be present in aqueous, methanol, and acetone extracts of the plant in qualitative phytochemical analysis.

Keywords: flemingia vestita, antibacterial activity, phytochemical screening, well diffusion method

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Authors: Kalyan Kumar Moulick

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In this paper the author studied the possibilities of using Rice Husk Ash (RHA) available in India; to produce concrete. The effect of RHA on concrete discussed. Traditional uses of Rice Husk in India pointed out and the advantages of using RHA in making concrete highlighted. Suggestion provided regarding prospective application of RHA concrete in India which in turn will definitely reduce the cost of concrete and environmental friendly due to utilization of waste and replacement of Cement.

Keywords: cement replacement, concrete, environmental friendly, rice husk ash

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Authors: Mohd Zuhair, Ram Babu Roy

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This paper presents an overview of the accessibility, design, and functioning of health insurance plans launched by state governments in India. In recent years, the governments of several states in India have come forward to provide health insurance coverage for the low-income group and rural population to reduce the out of pocket expenditure (OPE) on healthcare. Different health insurance schemes have different structures and offerings which differ in the different demographic factors. This study will portray a comparative analysis of the various health insurance schemes by analyzing different offerings and finance generation of the schemes. The comparative analysis will explain the lesson to be learned from these schemes and extend the existing knowledge of the health insurance in India. This would help in recognizing tension between various drivers and identifying issues pertaining to the sustainability of health insurance schemes in India.

Keywords: health insurance, out of pocket expenditure, universal healthcare, sustainability

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Authors: Tolulope Allo, Mofoluwake P. Ajayi, Adenike E. Idowu, Emmanuel O. Amoo, Fadeke Esther Olu-Owolabi

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Breast cancer which was more prevalent in Europe and America in the past is gradually being mirrored across the world today with greater economic burden on low and middle income countries (LMCs). Breast cancer is the most common cancer among women globally and current studies have shown that a woman dies with the diagnosis of breast cancer every thirteen minutes. The economic cost of breast cancer is overwhelming particularly for developing economies. While it causes billion of dollar in losses of national income, it pushes millions of people below poverty line. This study examined the economic burden of breast cancer on Nigerian women, its impacts on their standard of living and its effects on Nigeria’s socio economic development. The study adopts a qualitative research approach using the in-depth interview technique to elicit valuable information from respondents with cancer experience from the Southern part of Nigeria. Respondents constituted women in their reproductive age (15-49 years) that have experienced and survived cancer and also those that are currently receiving treatment. Excerpts from the interviews revealed that the cost of treatment is one of the major factors contributing to the late presentation of breast cancer incidences among women as many of them could not afford to pay for their own treatment. The study also revealed that many women prefer to explore other options such as herbal treatments and spiritual consultations which is less expensive and affordable. The study therefore concludes that breast cancer diagnosis and treatment should be subsidized by the government in order to facilitate easy access and affordability thereby promoting early detection and reducing the economic burden of treatment on women.

Keywords: breast cancer, development, economic burden, women

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Authors: Mangesh Govindrao Acharya

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The influence of religion on politics in India can be seen in the British period. The British used partition politics to create a schism between Hindus and Muslims in India. India was partitioned in1947 due to this policy of the British. In independent India, the principle of secularism was prioritized as a solution to this in the constitution created by the people. Secularism was provided for in 1978 by the 42nd Constitutional Amendment. Although India has embraced secularism, the role of religion in politics has not ended. Although 75 years of India's independence have been completed, politics is still done in the name of religion in India. Political parties choose their candidates, keeping in mind the influence of religion in a particular constituency. People think more about religion and caste while choosing their candidates. Caste riots occur due to the influence of religion-influenced politics. There is a new dispute between the minority and the majority. The Temple-Masjid controversy has become a focal point of Indian politics. Religious hatred in India is causing a huge loss of lives and property and is creating tension among the citizens. All the aspects of Indian politics that have been corrupted by religious fanaticism have been studied in this research paper. This paper mainly explores the causality of the influence of religion on Indian politics.

Keywords: religion, Indian politics, equality and justice, Muslim society, political parties

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Authors: Kalyan Koganti

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Background: In India, platelet transfusions are given to large no. of patients suffering from dengue due to the fear of bleeding especially when the platelet counts are low. Though many patients do not bleed when the platelet count falls to less than 20,000, certain patients bleed even if the platelet counts are more than 20,000 without any comorbid condition (like gastrointestinal ulcer) in the past. This fear has led to huge amounts of unnecessary platelet transfusions which cause significant economic burden to low and middle-income countries like India and also sometimes these transfusions end with transfusion-related adverse reactions. Objective: To identify the role of Activated Partial Thromboplastin Time (APTT) in comparison with thrombocytoenia as an indicator to assess the real need of platelet transfusions. Method: A prospective study was conducted at a hospital in South India which included 176 admitted cases of dengue confirmed by immunochromatography. APTT was performed in all these patients along with platelet count. Cut off values of > 60 seconds for APTT and < 20,000 for platelet count were considered to assess the bleeding manifestations. Results: Among the total 176 patients, 56 patients had bleeding manifestations like malena, hematuria, bleeding gums etc. APTT > 60 seconds had a sensitivity and specificity of 93% and 90% respectively in identifying bleeding manifestations where as platelet count of < 20,000 had a sensitivity and specificity of 64% and 73% respectively. Conclusion: Elevated APTT levels can be considered as an indicator to assess the need of platelet transfusion in dengue. As there is a significant variation among patients who bleed with respect to platelet count, APTT can be considered to avoid unnecessary transfusions.

Keywords: activated partial thromboplastin time, dengue, platelet transfusion, thrombocytopenia

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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: Esha Banerji

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This paper attempts an assessment of India's behaviour as a foreign policy actor amidst the COVID 19 pandemic by briefly surveying the various introductions and alterations made to India's foreign policy. First, the paper attempts to establish the key strategic pillars of Indian foreign policy after reviewing the existing works. It then proceeds to assess the prominent part played by Health Diplomacy ("Vaccine Maitri") in India's bilateral and multilateral relations during the pandemic and the role of the Indian diaspora in shaping India's foreign policy. This is followed by examining "India's Neighbourhood First policy" and the way it's been employed by the Indian government to extend India’s strategic influence during the pandemic. An empirical assessment will be done to examine the changing dynamics of India's relation with different regional groupings like SAARC, ASEAN, BIMSTEC, etc. The paper also explores the new alliances formed post-pandemic and India's role in them. This paper analyses the contemporary challenges that the largest nation in South Asia faces with the onset of a global pandemic and how Ancient Indian values like "Vasudhaiva Kutumbakam" have influenced India's foreign policy, especially during the pandemic. It also attempts to grasp the changes within the negotiation style of the Indian government, and the role played by various stakeholders in shaping India's position in the present geopolitical landscape. The study has been conducted using data collected from government records, External Affairs Ministry database, and other available literature. The paper concludes with an attempt to predict the far-reaching strategic implications that the policy, as mentioned above, may have for India.

Keywords: Indian foreign policy, COVID19, diplomacy, post pandemic world

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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: Krishnendu Mukhopadhyay, Subhashis Kundu, Mayank Tiwari, Sameeran Pani, Padmapal, Uttam Singh

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Blast Furnace is a counter current process where burden descends from top and hot gases ascend from bottom and chemically reduce iron oxides into liquid hot metal. One of the major problems of blast furnace operation is the erratic burden descent inside furnace. Sometimes this problem is so acute that burden descent stops resulting in Hanging and instability of the furnace. This problem is very frequent in blast furnaces worldwide and results in huge production losses. This situation becomes more adverse when blast furnaces are operated at low coke rate and high coal injection rate with adverse raw materials like high alumina ore and high coke ash. For last three years, H-Blast Furnace Tata Steel was able to reduce coke rate from 450 kg/thm to 350 kg/thm with an increase in coal injection to 200 kg/thm which are close to world benchmarks and expand profitability. To sustain this regime, elimination of irregularities of blast furnace like hanging, channeling, and scaffolding is very essential. In this paper, sustaining of zero hanging spell for consecutive three years with low coke rate operation by improvement in burden characteristics, burden distribution, changes in slag regime, casting practices and adequate automation of the furnace operation has been illustrated. Models have been created to comprehend and upgrade the blast furnace process understanding. A model has been developed to predict the process of maintaining slag viscosity in desired range to attain proper burden permeability. A channeling prediction model has also been developed to understand channeling symptoms so that early actions can be initiated. The models have helped to a great extent in standardizing the control decisions of operators at H-Blast Furnace of Tata Steel, Jamshedpur and thus achieving process stability for last three years.

Keywords: hanging, channelling, blast furnace, coke

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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: 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: Saroj Kumar Rath

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India's Muslims represent 15 percent of the nation's population, the world's third largest group in any nation after Indonesia and Pakistan. Extremist groups like the Islamic State, Al Qaeda, the Taliban and the Haqqani network increasingly view India as a target. Several trends explain the rise: Terrorism threats in South Asia are linked and mobile - if one source is batted down, jihadists relocate to find another Islamic cause. As NATO withdraws from Afghanistan, some jihadists will eye India. Pakistan regards India as a top enemy and some officials even encourage terrorists to target areas like Kashmir or Mumbai. Meanwhile, a stream of Wahhabi preachers have visited India, offering hard-line messages; extremist groups like Al Qaeda and the Islamic State compete for influence, and militants even pay jihadists. Muslims as a minority population in India could offer fertile ground for the extremist recruiters. This paper argues that there is an urgent need for the Indian government to profile militants and examine social media sites to attack Wahhabi indoctrination while supporting education and entrepreneurship for all of India's citizens.

Keywords: Al Qaeda, terrorism, Islamic state, India, haqqani network, Pakistan, Taliban

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

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

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

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

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

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

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

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

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

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

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

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

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Authors: Rupali Satsangi

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14 years ago, leaders from every country agreed on a vision for the future – a world with less poverty, hunger and disease, greater survival prospects for mothers and their infants, better educated children, equal opportunities for women, and a healthier environment; a world in which developed and developing countries work in partnership for the betterment of all. This vision took the shape of eight Millennium Development Goals, which provide countries around the world a framework for development and time-bound targets by which progress can be measured. However, India has found 35 of the indicators as relevant to India. India’s MDG-framework has been contextualized through a concordance with the existing official indicators of corresponding dimensions in the national statistical system. The present study based on secondary data analyzed the status of India towards achieving the MDGs after reviewing the data study find out that India can miss the MDGs Bus in women health, sanitation and global partnership. These goals were less addressed by India in his policies and takeoffs.

Keywords: millennium development goals, national statistical system, global partnership, healthier environment

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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: Samir Sarfraj Terdalkar

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India needs to step into affordable higher education with more focus on skill development and employability. The general scenario of higher education in India revolves around two major branches of higher education ie., Engineering and Medical Sciences. These two branches still cannot be considered as affordable. Hence, skill development of each and every student beginning from the school education should emphasize on learning skills with special focus on physics and mathematics. In India, the Central Government initiated a survey based process of all higher Educational Institutes/ Universities and colleges in India. This survey/ process was – All India Survey On Higher Education (AISHE). The focus of this process was understand and Though the increase is significant, it is necessary to propagate skill and vocational education which would add to the employability factor. Similarly, there has been a significant increase in number of higher education institutes, there is need to rethink on the type of education/ curriculum offered by these institutions. In this regard, vocational education has helped to build skill sets to certain extent. There is need to bring in this vocational educational in main stream education which could be complementary for undergraduate / post graduate education. The paper focuses on different policies to bring in vocational/ skill education.

Keywords: higher education, skill, vocational, India

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Authors: Fayiz Saifurahman

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Afghanistan's geopolitically and geo-strategically location has remained the attention of Indian policy. On 11 September 2001, the terrorist attacks in the United States and the announcement of the United States, fight for international war against the Taliban in November 2001 provided India a chance to pursue its foreign policy goals of achieving a good position in the region and emerging as an international power. Therefore, post-9/11, India strengthened its efforts to re-establish its power in Afghanistan. The objectives of this study are to study the India-Afghanistan relation in the post 9/11 and to discuss the initial role of India in Afghanistan. The research method was conducted on a qualitative method based on descriptive. The research findings propose that; Indian foreign policy should be analyzed and increase its soft power. Afghanistan has definitely provided a significant occasion for India to increase its power in Afghanistan. In this linkage, Indian determinations have been to intrude all parts in Afghanistan to make them reliant on Indian cooperation.

Keywords: Afghanistan, war, power, policy.

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Authors: Pellecchia M. T., Savarese G., Carpinelli L., Calabrese M.

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Introduction: Parkinson's disease (PD) is characterized by a progressive loss of autonomy which undoubtedly has a significant impact on the quality of life of caregivers, and parents are the main informal caregivers. Caring for a person with PD is associated with an increased risk of psychiatric morbidity and persistent anxiety-depressive distress. The aim of the study is to investigate the burden on caregivers of patients with PD, through the use of multidimensional scales and to identify their personological and environmental determinants. Methods: The study has been approved by the Ethic Committee of the University of Salerno and informed consent for participation to the study was obtained from patients and their caregivers. The study was conducted at the Neurology Department of the A.O.U. "San Giovanni di Dio and Ruggi D’Aragona" of Salerno between September 2020 and May 2021. Materials: The questionnaires used were: a) Caregiver Burden Inventory - CBI a questionnaire of 24 items that allow identifying five sub-categories of burden (objective, psychological, physical, social, emotional); b) Depression Anxiety Stress Scales Short Version - DASS-21 questionnaire consisting of 21 items and valid in examining three distinct but interrelated areas (depression, anxiety and stress); c) Family Strain Questionnaire Short Form - FSQ-SF is a questionnaire of 30 items grouped in areas of increasing psychological risk (OK, R, SR, U); d) Zarit Caregiver Burden Inventory - ZBI, consisting of 22 items based on the analysis of two main factors: personal stress and pressure related to his role; e) Life Satisfaction, a single item that aims to evaluate the degree of life satisfaction in a global way using a 0-100 Likert scale. Findings: N ° 29 caregivers (M age = 55.14, SD = 9.859; 69% F) participated in the study. 20.6% of the sample had severe and severe burden (CBI score = M = 26.31; SD = 22.43) and 13.8% of participants had moderate to severe burden (ZBI). The FSQ-SF highlighted a minority of caregivers who need psychological support, in some cases urgent (Area SR and Area U). The DASS-21 results show a prevalence of stress-related symptoms (M = 10.90, SD = 10.712) compared to anxiety (M = 7.52, SD = 10.752) and depression (M = 8, SD = 10.876). There are significant correlations between some specific variables and mean test scores: retired caregivers report higher ZBI scores (p = 0.423) and lower Life Satisfaction levels (p = -0.460) than working caregivers; years of schooling show a negative linear correlation with the ZBI score (p = -0.491). The T-Test indicates that caregivers of patients with cognitive impairment are at greater risk than those of patients without cognitive impairment. Conclusions: It knows the factors that affect the burden the most would allow for early recognition of risky situations and caregivers who would need adequate support.

Keywords: anxious-depressive axis, caregivers’ burden, Parkinson’ disease, psychological risks

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