Pathogenic mechanisms involved in the ocular immunoinflammatory lesions : herpetic stromal keratitis

Herpes simplex virus infection of the ocular tissue induces a blinding immunoinflammatory lesion, Herpetic Stromal Keratitis (HSK). In mice of susceptible strains, a similar lesion can be induced following a primary infection mode. Virus infection induces an acute short lived epithelial keratitis. At this time, an immune cell infiltration of polymorpho nuclear leukocytes, mainly neutrophils are seen in the underlying stroma. The virus is usually cleared by days 5-6 post infection and the cornea assumes a state of normalcy. The chronic phase of the immunoinflammatory process begins around day 7 post infection in the absence of replicating virus. The primary cells mediating the lesion are CD4+ , T cells of the Th1 cytokine producing phenotype. Accordingly, SCID mice or athymic nude mice fail to support HSK lesions unless reconstituted with CD4+ T cell subsets. The absence of inciting virus during the course of clinical phase of the lesion implies that HSK might represent an autoimmune lesion. Several hypotheses have been put forth to explain the nature of the agonists driving the CD4+ T cells in the cornea in HSK lesion. The main ideas include persistence of viral antigens in the cornea, alternatively the role of virus encoded molecular mimic in inducing autoimmune lesion and HSK as a consequence of bystander activation of CD4+ T cells. In the present study, an attempt has been made to understand the role of the three mechanisms in the HSK pathogenesis. Experiments were designed to address the role of virus and viral antigens in lesion development with use of SCID reconstitution and replication defective virus mutants. The role of the immune response in HSK was tested by evaluating cross reactive responses to putative agonists following immunization or tolerization experiments. A number of transgenic and knockout mice were used to obtain mechanistic evidence for many of the hypotheses. Part I consists of a general introduction and overview of mechanisms involved in viral pathogenesis in general and HSK specifically. Part II is devoted to the analysis of autoantigen and molecular mimicry hypothesis in HSK pathogenesis. The results cast doubts over the role of IgG2a and UL6 as agonists driving the immunoinflammatory reaction. An explanation for the susceptibility of mice lacking B cells or the IgG2a autoantigen to HSK is provided in Part III of the dissertation. These results suggest that in the absence of B cells two mechanisms may contribute to lesion severity: biased Thl response and the spread and persistence of virus to the corneal stroma, which is the site of inflammation. Part IV and V are devoted to the understanding of bystander activation as a model for HSK. In Part IV, bystander activation as an exclusive means of immunopathology is demonstrated in Pigeon Cytochrome C CD4+ TCR transgenic mice. Part V is aimed at understanding the role of bystander activation in HSK in immunocompetent mice. Cytokine knockout TCR transgenic mice were also used in this study to examine the components of the immune system responsible for non specific activation of CD4+ T cells. The results in these sets of experiments suggest that the activating stimuli determine the contribution of bystander activation in the ocular lesion. In the absence of IFN y, activation stimuli for bystander CD4+ T cells are insufficient for lesion induction

Preferences based Customized Trust Model for Assessment of Cloud Services

In cloud environment, many functionally similar cloud services are available. But, the services differ in Quality of Service (QoS) levels, offered by them. There is a diversity in user requirements about the expected qualities of cloud services. Trust is a measure to understand whether a cloud service can adequately meet the user requirements. Consequently, trust assessment plays a significant role in selecting the suitable cloud service. This paper proposes preferences based customized trust model (PBCTM) for trust assessment of cloud services. PBCTM takes into account user requirements about the expected quality of services in the form of preferences. Accordingly, it performs customized trust assessment based on the evidences of various attributes of cloud service. PBCTM enables elastic trust computation, which is responsive to dynamically changing user preferences with time. The model facilitates dynamic trust based periodic selection of cloud services according to varying user preferences. Experimental results demonstrate that the proposed preferences based customized trust model outperforms the other model in respect of accuracy and degree of satisfaction

Governing nutrition, performing state: workers of the Integrated Child Development Services (ICDS) programme, India

The failures of state implemented development programmes have been largely attributed to governance issues. I study one of the largest child development programmes in the world, the Integrated Child Development Services (ICDS) programme of India to understand how its governance is determined and gaps between design and practice produced. Building on a non-normative concept of governance, my research ethnographically examines the everyday processes and practices of the ICDS, through ten months of fieldwork in a community development block of Aurangabad District, Maharashtra. State practices have been studied but the role of state functionaries has not been adequately addressed. I research everyday state practices as performative - negotiated and constructed by ICDS functionaries in interaction with the local politics of caste, vertical systems of ‘corruption’ and initiatives of bureaucratic reform. I find that ICDS functionaries use state practices to: (a) perform caste, exercising dominance but also contesting caste-based subordination, (b) develop and manage informal systems of financial practices, and (c) stage performance to make it appear as if targets have been met and rules followed. The improvisation of programme practices by ICDS functionaries generates gaps and variations from programme design including the dominant caste capture of field level ICDS positions, exclusion of Scheduled Caste beneficiaries and localities from programme benefits and manipulation of programme records and performance audits. But such improvisation is also facilitative providing sites for challenging the dominant political and social order and enabling the delivery of ICDS services despite resource poor contexts and unsuitable programme rules. These findings suggest that ICDS governance at the sub-district or implementation level is determined in interaction with the politics of caste and the un-implementability of bureaucratic rules. Additionally, I highlight that implementation gaps do not always reflect the incapacity of state functionaries but may also represent their ingenuity in constrained circumstances

Concept of Gudavarti w.s.r. to Rectal Suppositories

Suppositories are solid dosage preparations prepared by moulding or compression intended for its insertion into body orifices like the rectum, vagina and the urethra. Suppositories melts and exhibits local or systemic effects. Rectal route of drug administration encorporates absorption of the drug through rectal blood vessels to exhibit desired therapeutic action. Rectal suppositories can be the best choice for drugs that are either too irritative to the gut or more effective when partly metabolized by the liver. Varti Kalpana is a variant of Vati Kalpana with similar method of preparation. Varti are solid and are wick shaped with tapering ends intended for easy insertion into body orifices. Based on the site of insertion, Ayurveda explains Guda Varti, Yoni Varti and Sishna Varti. Different types of Varti have been explained based on its size, site of application, composition and action. Various methods of its preparation has been explained both in the classical literature and in contemporary science. Rectal suppositories offer patients an option that is less invasive and less discomforting and which proves to be a convenient drug delivery option especially in patients with rectal complaints. It can be appreciated that Varti Kalpana was used in practice since ancient times and that recent advancement of suppositories is just its slight modification. A detailed study of both the Varti and the suppositories help us draw many similarities between the two

AYURVEDIC MANAGEMENT OF GUILLAIN-BARRÉ SYNDROME: A CASE STUDY

Guillain-Barré syndrome is a disorder which is caused by the body's immune system attacking its own peripheral nervous system. The syndrome afflicts about one person in 100,000. Either gender can be affected in any age group especially between ages 30 and 50, however risk increases with age. It often follows a minor infection Most of the time, signs of the original infection have disappeared before the symptoms of Guillain-Barré begin. Guillain-Barré syndrome damages parts of nerves. This nerve damage causes tingling, muscle weakness, and paralysis. Guillain-Barré syndrome most often affects the nerve's covering (myelin sheath). Such damage is called demyelination and it causes nerve signals to move more slowly. Damage to other parts of the nerve can cause the nerve to stop working altogether. It is a paralyzing syndrome which can have dire consequences if not managed by an informed medical team. This article will explain how this disorder begins, how it is managed in Ayurveda. It can be compared to Kaphavruta vyana, so approach is to treat Kapha first and then to Vata with Brihmana chikitsa

A Brief Bibliometric Survey of Leukemia Detection by Machine Learning and Deep Learning Approaches

Background: This study aims to analyze the work done on leukemia detection and diagnosis using machine learning, deep learning and different image processing techniques from 2011 to 2020, using the bibliometric methods. Methods: different articles on leukemia detection were retrieved using one of the most popular database- Scopus. The research articles are considered between 2011 to 2020. Scopus analyzer is used for getting some analysis results such as documents by year, source, county and so on. VOSviewer Version 1.6.15 is used for the analysis of different units such as co-authorship, co-occurrences, citation analysis etc. Results: In our study, a database search outputs a total of 617 articles on leukemia detection from 2011 to 2020. Statistical analysis and network analysis shows the maximum articles are published in the years 2019 and 2020 with India contributed the largest number of documents. Network analysis of different parameters shows a good potential of the topic in terms of research. Conclusions: Scopus keyword search outcome has 617 articles with English language having the largest number. Authors, documents, country, affiliation etc are statically analyzed and indicates the potential of the topic. Network analysis of different parameters indicates that, there is a lot of scope to contribute in the further research in terms of advanced algorithms of computer vision, deep learning and machine learning

Heavy metal, salinity and azo dye tolerant, Cr (VI) reducing, plant growth-promoting Pseudomonas aeruginosa R32 reverses Cr (VI) biotoxic effects in Vigna mungo

Hexavalent chromium [Cr (VI)], derived from various industries, including fly ash from coal-based Thermal Power Plants, can be a source of toxic pollution of land and water bodies. This study aimed to bioremediation of such pollutant dump sites using bacteria capable of both Cr(VI) reduction and plant growth-enhancing substance production. The bacteria were isolated from the rhizospheric fly ash of a Thermal Power Plant, Kanpur. One of the rhizospheric isolate, Pseudomonas aeruginosa R32 showed high minimum inhibitory concentration (MIC) for Cr(VI) (1250 µg/ml), heavy metal tolerance (ZnCl2, CdCl2, Pb(NO3)2) up to 100 µg/ml, Acid Red 249 (AR) tolerance and halotolerance (6% NaCl). The isolate R32 also produces plant growth-promoting (PGP) hormones in the absence or presence of Cr (VI). R32 could completely reduce Cr(VI) at a tested dose of 100 and 500 μg/ml after 24h and 72h, respectively. However, decolorization of AR was observed after 48 hours at an initial concentration of 100 µg/ml and confirmed by Fourier transform infrared spectroscopy analysis. Vigna mungo seed inoculation with isolate R32 showed increased rootling growth compared to shoot after 7 d treatment with 0, 100, 500, and 1000 μg/ml of Cr(VI) concentrations, respectively. Root length tolerance index in Cr(VI) treated V. mungo seedlings was reduced to 56%, 35%, and 29%, respectively, when treated with 100, 500, and 1000 μg/ml Cr(VI) in comparison to control. Cr(VI) sub-MIC concentrations can affect the plant growth-promoting properties of rhizospheric bacteria. Herein, we report the isolation of rhizospheric bacteria P. aeruginosa R32 showing concurrent PGP substance production and Cr(VI) bioreduction capabilities in the presence of PGP inhibitory Cr(VI) concentrations.

Concentration Dependent Effect of Azadirachta indica (Neem) Seed Oil and Neem Bark extract on Planktonic and Established Biofilm Growth of Pseudomonas aeruginosa and Staphylococcus aureus

Azadirachta indica Juss (Neem) is well documented for its antimicrobial activity. The effect of varying concentrations (0.1 to 50% v/v) of Azadirachta indica derived neem seed oil (NSO), neem seed oil with tween 20 and neem bark extract was evaluated on planktonic, biofilm formation and mature biofilms of multiple drug resistant Pseudomonas aeruginosa ATCC 15442 and Staphylococcus aureus ATCC 25923 using the crystal violet assay and scanning electron microscopy. NSO showed antimicrobial activity at 25% v/v for P. aeruginosa but not S. aureus in zone of inhibition assay. Neem bark extract on the contrary showed antimicrobial activity against both the isolates at 50% v/v concentrations. Interestingly, in biofilm formation assay, low concentrations of NSO (3.5 to 0.2% v/v) induced biofilm formation while inhibition of both planktonic and biofilm was seen in concentration dependent manner from 12.5% v/v onwards. Complex of NSO and tween in comparison of NSO alone caused low induction in S.aureus biofilm formation, while inhibiting biofilm formation of P. aeruginosa at all the concentrations. In biofilm eradication assay, NSO induced biofilm of both P. aeruginosa (50 to 0.1%v/v) and S. aureus (50 to 3.13%v/v). Eradication effect of neem bark extract was found on P. aeruginosa biofilm in a dose dependent fashion from 50 to 20% v/v followed by 0.2 to 0.1%v/v concentration respectively. S. aureus biofilm were eradicated at 50 to 25%v/v concentrations. At low concentrations, both the neem derivatives induced biofilm mediated growth of the pathogenic organisms. The data also indicate that neem seed oil was more effective against Gram negative P. aeruginosa while neem bark extract was effective against Gram positive S. aureus. This study highlights the crucial but variable effects of concentration dependent effect of phytochemicals and their composition on biofilm induction as well as eradication, the primary growth form in clinical settings. This challenges the notion that all herbal products are safe as antimicrobial activities differ as per microbial growth modes. Hence, concentration dependent effect of medicinal plant derived products requires thorough investigation prior to their use as antimicrobial agents

Association of Vegetable and Animal Flesh Intake with Inflammation in Pregnant Women from India

In pregnant women, studies are lacking on the relationship of vegetable and animal flesh (poultry, red meat and seafood) intake with inflammation, especially in low- and middle-income countries. We conducted a cohort study of pregnant women receiving antenatal care at BJ Medical College in Pune, India. The dietary intake of pregnant women was queried in the third trimester using a validated food frequency questionnaire. Twelve inflammatory markers were measured in plasma samples using immunoassays. Only 12% of the study population were vegetarians, although animal flesh intake levels were lower compared to Western populations. In multivariable models, higher intakes of total vegetables were associated with lower levels of the T-helper (Th) 17 cytokine interleukin (IL)-17a (p = 0.03) and the monocyte/macrophage activation marker soluble CD163 (sCD163) (p = 0.02). Additionally, higher intakes of poultry were negatively associated with intestinal fatty-acid binding protein (I-FABP) levels (p = 0.01), a marker of intestinal barrier dysfunction and Th2 cytokine IL-13 (p = 0.03), and higher seafood was associated with lower IL-13 (p = 0.005). Our data from pregnant women in India suggest that a higher quality diet emphasizing vegetables and with some animal flesh is associated with lower inflammation. Future studies should confirm these findings and test if modulating vegetables and animal flesh intake could impact specific aspects of immunity and perinatal health