T cell subsets and disease mechanisms in inflammatory myopathies

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of chronic muscle disorders, typically displaying infiltrating T cells in skeletal muscle tissue and classified into polymyositis, dermatomyositis and sporadic inclusion body myositis. Several studies involving both humans and animal models point towards a role for T cells in the pathogenesis of IIMs, however, the precise phenotype, functionality and specificity of pathogenic T cells remain elusive. Increased frequencies of a subset of T cells, known as CD28null T cells, in peripheral blood and affected organs in various chronic inflammatory disorders, are reported by several studies. Such CD28null T cells are highly differentiated T cells lacking the co-stimulatory molecule CD28, which acquire expression of other receptors commonly associated with natural killer cells, and display proinflammatory, cytotoxic and apoptosis resistant features. In contrast to CD28null T cells, regulatory T cells are T cell subset critical for maintaining immune tolerance and also described to assist in the muscle repair process. The aims of this thesis were to investigate CD28null T cell subsets in both muscle tissue and peripheral blood of patients with IIMs, by evaluating frequencies, phenotype, function and clinical relevance of these cells. The cytotoxic mechanisms of CD28null T cells towards autologous muscle cells were investigated using in vitro T cell - muscle cell co-cultures. Muscle tissues of patients were investigated for the effects of conventional immunosuppressive therapies on CD28null and regulatory T cell subsets. Glucocorticoid and regulatory T cells mediated immunosuppressive effects on circulating CD28nulls T cells were evaluated using in vitro assays. We demonstrate that muscle-infiltrating T cells are predominantly CD4+CD28null and CD8+CD28null T cells in patients with polymyositis and dermatomyositis. Also in sporadic inclusion body myositis, where the role of immune system is controversial, T cell infiltrates in muscle tissue are dominated by CD28null T cells. Circulating CD28null T cell subsets of both CD4 and CD8 lineage were more common in patients compared to healthy controls, and were associated with human cytomegalovirus infection. These cells displayed oligoclonal expansions, proinflammatory cytokine secretion and degranulation potential, and also contained perforin. Using autologous in vitro co-cultures, we showed that the cytotoxic effects of CD28null T cells towards muscle cells are mediated largely via perforin-dependent mechanisms and regulated by IFNγ-induced HLA expression on muscle cells. Interestingly, poor clinical response in patients following immunosuppressive therapy was linked to persistence of CD28null T cells in muscle tissue. CD4+CD28null T cells were also found to be resistant towards glucocorticoid and regulatory T cell mediated immunosuppression in in vitro assays. These findings imply that CD28null T cells represent clinically important effector cells in IIMs, capable of attacking muscle fibers and inducing chronic inflammation mediated pathogenesis. Ineffectiveness of current immunosuppressive therapies appears to be linked with persistent CD28null T cells in muscle tissue as well as their immunosuppression resistant properties; therefore, these cells represent potential target candidates for future therapies

Cost of Menstrual Hygiene Practices in Gujarat, India

Menstrual cycles are an integral part of a nearly two-third of a woman’s life, and occur every month. Menstruation is a public health concern because irrespective of whether a woman can afford hygienic absorbents or not, she undergoes menstruation phase every month. Therefore, menstruation requires to be examined from public health policy perspective. Choice of menstrual products is not only subject to budget constraint but also to “other regarding preferences”, as can be explained by behavioural economics theories. This study therefore, seeks to get insights into the determinants of choice of menstrual product. The study attempts to devise a method of estimating the minimum yearly cost of menstrual hygiene and also provides an estimate for the same, which can be helpful for the policy prescription. The study is undertaken in Gujarat (India), from a cross-section of districts (developed, developing and tribal), and also a cross-section of socioeconomic status and age. A total of 1025 responses are collected and analysed to get insights into product preferences and resultant cost. The study finds that it is economical to make use of menstrual cups, however, cultural constrains might restrict its use

Cost of Menstrual Hygiene Practices in Gujarat, India

Menstrual cycles are an integral part of a nearly two-third of a woman’s life, and occur every month. Menstruation is a public health concern because irrespective of whether a woman can afford hygienic absorbents or not, she undergoes menstruation phase every month. Therefore, menstruation requires to be examined from public health policy perspective. Choice of menstrual products is not only subject to budget constraint but also to “other regarding preferences”, as can be explained by behavioural economics theories. This study therefore, seeks to get insights into the determinants of choice of menstrual product. The study attempts to devise a method of estimating the minimum yearly cost of menstrual hygiene and also provides an estimate for the same, which can be helpful for the policy prescription. The study is undertaken in Gujarat (India), from a cross-section of districts (developed, developing and tribal), and also a cross-section of socioeconomic status and age. A total of 1025 responses are collected and analysed to get insights into product preferences and resultant cost. The study finds that it is economical to make use of menstrual cups, however, cultural constrains might restrict its use

Ayurvedic management of Leukoplakia - A Case Study

Oral leukoplakia (OL) is a premalignant lesion described as “a predominant white lesion of the oral mucosa which cannot be defined as any other known lesion”. OL located on the floor of the mouth, soft palate and tongue are considered as high-risk lesions, while, in other areas, they may be considered as of low malignancy risk. A Forty five years old male patient had complaints of white lesion on left lat. Surface of tongue, along with burning sensation since 4-5 months. He was diagnosed with Leukoplakia and he had taken allopathic medicine for 4 to 5 times, but it was inversely relapsed, so he was treated with Pratisarana of Bibhitaka Churna and Rasayana Churna, Yastimadhu Ghanavati as lozenges along with Rasayana tablets orally for a period of 6 months. After 6 month therapy, white lesion became disappear and no burning sensation. Thus this patient was successfully treated with above therapy with no recurrence or any complications till date

Design and synthesis of novel s-triazine based coumarin, quinoline, morpholine and isoniazid derivatives and their antitubercular and antimicrobial evaluation

285-292This study presents the synthesis of novel s-triazine derivatives. The synthetic route to final s-triazines consists of two nucleophilic substitution reactions of 4-hydroxy benzonitrile and 8-hydroxyquinoline or 8-hydroxy-7-methyl coumarin or isoniazid or morpholine with 2,4,6-trichloro-1,3,5-triazine resulting in 2,4-disubstituted-6-chloro-1,3,5-triazine derivatives to introduce the various amines functionality. The structures of the compounds have been elucidated with the aid of IR, 1H and 13C NMR, mass spectroscopy and elemental analysis. The title compounds have then been investigated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv strain by using BACTEC MGIT and Lowenstein-Jensen MIC method and antimicrobial evaluation

Aperture-Fed Quad-Port Dual-Band Dielectric Resonator-MIMO Antenna for Sub-6 GHz 5G and WLAN Application

A four-port dielectric resonator-based connected ground multiple-input multiple-output (MIMO) antenna is designed. The presented antenna was excited through the aperture feeding technique. The dual bands are achieved by optimally feeding the rectangular dielectric resonator through engineered triangular slots. The antenna has operating modes of TE111X and TE111Y at 4.5 GHz and 5 GHz, respectively. It presents a 2 : 1 VSWR bandwidth of 2.64% (4.48 GHz-4.60 GHz) and 1.2% (4.96 GHz-5.04 GHz) in the lower and upper bands, respectively. The edge-to-edge distance between array elements is around 7.5 mm. The single antenna dimension is 30 mm x 30 mm, whereas the four-port antenna dimension is 60 mm x 60 mm. The optimum isolation was achieved by carefully placing the antenna elements on the substrate through multiple iterations. The antenna provides port isolation better than 20 dB at both resonances with full ground profile. The advantage of the antenna is that it provides fair antenna and MIMO parameters without additional isolation techniques. The antenna has efficiency in order of 88.02% and 86.31%. The peak gain is 7.67 dBi and 8.32 dBi at 4.5 GHz and 5 GHz, respectively. The optimum envelope correlation coefficient (ECC) is 0.037, channel capacity coss (CCL) is 0.2 bits/sec/Hz, diversity gain (DG) is 9.99 dB, and total active reflection coefficient (TARC) is -18.87. The antenna elements are orthogonally placed with adequate separation to achieve polarization diversity and spatial diversity. The antenna provides the utilization in Sub-6 GHz 5G and WLAN communication applications

Additions and Corrections

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Design and synthesis of novel s-triazine based coumarin, quinoline, morpholine and isoniazid derivatives and their antitubercular and antimicrobial evaluation

This study presents the synthesis of novel s-triazine derivatives. The synthetic route to final s-triazines consists of two nucleophilic substitution reactions of 4-hydroxy benzonitrile and 8-hydroxyquinoline or 8-hydroxy-7-methyl coumarin or isoniazid or morpholine with 2,4,6-trichloro-1,3,5-triazine resulting in 2,4-disubstituted-6-chloro-1,3,5-triazine derivatives to introduce the various amines functionality. The structures of the compounds have been elucidated with the aid of IR, 1H and 13C NMR, mass spectroscopy and elemental analysis. The title compounds have then been investigated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv strain by using BACTEC MGIT and Lowenstein-Jensen MIC method and antimicrobial evaluation

Comparative evaluation of two subgingival irrigating solutions in the management of periodontal disease: A clinicomicrobial study

Context: Local administration of antimicrobial agents offer a “site-specific” approach to the periodontal therapy and it has several benefits. Aim: The present study was aimed to assess the clinical and microbial changes by subgingival irrigation using different subgingival irrigants in periodontitis patients and also to assess the mechanical effect of different local irrigation devices; if any. Settings and Design: Split-mouth design was employed on ten individuals. Materials and Methods: The study sample consisted of 10 individuals in whom full-mouth scaling and root planing was performed and subgingival irrigation therapy was instituted for an experimental period of 30 days. The clinical as well as microbiological parameters were evaluated. Statistical Analysis Used: To calculate baseline data with day thirty data,paired t-test was used. Intergroup comparison was carried out using one-way ANOVA. Multiple comparisons among groups were carried out using post hoc Tamhane's T2 test. Results: Among the different subgingival irrigants used, 0.2% chlorhexidine gluconate is most effective followed by ozonated water, whereas saline was found to be ineffective when compared to the other two subgingival irrigants. Subgingival irrigation using pulsated device may not have any additive effect in alteration of the subgingival microflora. Conclusion: Within the limits and scope of the study, it can be safely concluded that 0.2% chlorhexidine may be used as an adjunct to mechanical therapy for achieving a significant reduction in inflammatory periodontal changes and also reduction in periodontopathogenic microflora