Histopathological features of relapse cases in leprosy

Leprosy is unique in terms of the nature of the causative organism (Mycobacterium leprae), the chronicity of the disease, its prolonged treatment and the definitions of “cure” and “relapse.” The principal mode of assessing the efficacy of therapeutic regimens in leprosy is the “relapse rate.” There are wide variations in estimates of relapse rates after the World Health Organization (WHO) multidrug therapy in different regions. The important predisposing factors for relapse include the presence of “persister” bacilli, monotherapy, inadequate/irregular therapy, presence of multiple skin lesions/thickened nerves and lepromin negativity. The conventional methods of confirming activity or relapse in an infectious disease (demonstration and/or culture of the etiologic agent) have limited utility in leprosy because of the difficulty in demonstrating bacilli in paucibacillary (PB) cases and absence of a method of in vitro cultivation of M. leprae. Bacteriological parameters are useful in multibacillary (MB) leprosy, whereas in PB leprosy, the criteria for relapse depend primarily on clinical features. Although there are no widely available serologic tests for leprosy other than in a research setting, various immunological tests may be useful for monitoring patients on chemotherapy as well as for confirming suspected cases of relapse. The main differential diagnoses for relapse are reversal reactions, erythema nodosum leprosum and reactivation/resistance/reinfection. The most reliable criteria for making an accurate diagnosis of relapse include clinical, bacteriological and therapeutic criteria. Additional ones that may be used, depending on the setting, are histopathological and serologic criteria

Pathogenesis of bullous erythema nodosum leprosum: a case report

A 54 years old male, presented with acute onset of fever, malaise and body ache and multiple painful reddish swellings and fluid filled lesions in different parts of body. He gave history suggestive of several earlier episodes of type 2 lepra reactions with erythema nodosum leprosum lesions which were managed with corticosteroids. Dermatological examination revealed multiple erythematous tender nodules and plaques on face, extremities and trunk. He also had multiple bullous lesions on trunk. Investigations revealed polymorphonuclear leukocytosis and raised ESR. Biochemical investigations were normal. Slit skin smear examination showed fragmented acid fast bacilli with bacteriological index of 5+

Influence of culture conditions on the molecular signature of mesenchymal stem cells

Cell based therapies require cells capable of self renewal and differentiation, and a prerequisite is the ability to prepare an effective dose of ex vivo expanded cells for autologous transplants. The in vivo identification of a source of physiologically relevant cell types suitable for cell therapies is therefore an integral part of tissue engineering. Bone marrow is the most easily accessible source of mesenchymal stem cells (MSCs), and harbours two distinct populations of adult stem cells; namely hematopoietic stem cells (HSCs) and bone mesenchymal stem cells (BMSCs). Unlike HSCs, there are yet no rigorous criteria for characterizing BMSCs. Changing understanding about the pluripotency of BMSCs in recent studies has expanded their potential application; however, the underlying molecular pathways which impart the features distinctive to BMSCs remain elusive. Furthermore, the sparse in vivo distribution of these cells imposes a clear limitation to their in vitro study. Also, when BMSCs are cultured in vitro there is a loss of the in vivo microenvironment which results in a progressive decline in proliferation potential and multipotentiality. This is further exacerbated with increased passage number, characterized by the onset of senescence related changes. Accordingly, establishing protocols for generating large numbers of BMSCs without affecting their differentiation potential is necessary. The principal aims of this thesis were to identify potential molecular factors for characterizing BMSCs from osteoarthritic patients, and also to attempt to establish culture protocols favourable for generating large number of BMSCs, while at the same time retaining their proliferation and differentiation potential. Previously published studies concerning clonal cells have demonstrated that BMSCs are heterogeneous populations of cells at various stages of growth. Some cells are higher in the hierarchy and represent the progenitors, while other cells occupy a lower position in the hierarchy and are therefore more committed to a particular lineage. This feature of BMSCs was made evident by the work of Mareddy et al., which involved generating clonal populations of BMSCs from bone marrow of osteoarthritic patients, by a single cell clonal culture method. Proliferation potential and differentiation capabilities were used to group cells into fast growing and slow growing clones. The study presented here is a continuation of the work of Mareddy et al. and employed immunological and array based techniques to identify the primary molecular factors involved in regulating phenotypic characteristics exhibited by contrasting clonal populations. The subtractive immunization (SI) was used to generate novel antibodies against favourably expressed proteins in the fast growing clonal cell population. The difference between the clonal populations at the transcriptional level was determined using a Stem Cell RT2 Profiler TM PCR Array which focuses on stem cell pathway gene expression. Monoclonal antibodies (mAb) generated by SI were able to effectively highlight differentially expressed antigenic determinants, as was evident by Western blot analysis and confocal microscopy. Co-immunoprecipitation, followed by mass spectroscopy analysis, identified a favourably expressed protein as the cytoskeletal protein vimentin. The stem cell gene array highlighted genes that were highly upregulated in the fast growing clonal cell population. Based on their functions these genes were grouped into growth factors, cell fate determination and maintenance of embryonic and neural stem cell renewal. Furthermore, on a closer analysis it was established that the cytoskeletal protein vimentin and nine out of ten genes identified by gene array were associated with chondrogenesis or cartilage repair, consistent with the potential role played by BMSCs in defect repair and maintaining tissue homeostasis, by modulating the gene expression pattern to compensate for degenerated cartilage in osteoarthritic tissues. The gene array also presented transcripts for embryonic lineage markers such as FOXA2 and Sox2, both of which were significantly over expressed in fast growing clonal populations. A recent groundbreaking study by Yamanaka et al imparted embryonic stem cell (ESCs) -like characteristic to somatic cells in a process termed nuclear reprogramming, by the ectopic expression of the genes Sox2, cMyc and Oct4. The expression of embryonic lineage markers in adult stem cells may be a mechanism by which the favourable behaviour of fast growing clonal cells is determined and suggests a possible active phenomenon of spontaneous reprogramming in fast growing clonal cells. The expression pattern of these critical molecular markers could be indicative of the competence of BMSCs. For this reason, the expression pattern of Sox2, Oct4 and cMyc, at various passages in heterogeneous BMSCs population and tissue derived cells (osteoblasts and chondrocytes), was investigated by a real-time PCR and immunoflourescence staining. A strong nuclear staining was observed for Sox2, Oct4 and cMyc, which gradually weakened accompanied with cytoplasmic translocation after several passage. The mRNA and protein expression of Sox2, Oct4 and cMyc peaked at the third passage for osteoblasts, chondrocytes and third passage for BMSCs, and declined with each subsequent passage, indicating towards a possible mechanism of spontaneous reprogramming. This study proposes that the progressive decline in proliferation potential and multipotentiality associated with increased passaging of BMSCs in vitro might be a consequence of loss of these propluripotency factors. We therefore hypothesise that the expression of these master genes is not an intrinsic cell function, but rather an outcome of interaction of the cells with their microenvironment; this was evident by the fact that when removed from their in vivo microenvironment, BMSCs undergo a rapid loss of stemness after only a few passages. One of the most interesting aspects of this study was the integration of factors in the culture conditions, which to some extent, mimicked the in vivo microenvironmental niche of the BMSCs. A number of studies have successfully established that the cellular niche is not an inert tissue component but is of prime importance. The total sum of stimuli from the microenvironment underpins the complex interplay of regulatory mechanisms which control multiple functions in stem cells most importantly stem cell renewal. Therefore, well characterised factors which affect BMSCs characteristics, such as fibronectin (FN) coating, and morphogens such as FGF2 and BMP4, were incorporated into the cell culture conditions. The experimental set up was designed to provide insight into the expression pattern of the stem cell related transcription factors Sox2, cMyc and Oct4, in BMSCs with respect to passaging and changes in culture conditions. Induction of these pluripotency markers in somatic cells by retroviral transfection has been shown to confer pluripotency and an ESCs like state. Our study demonstrated that all treatments could transiently induce the expression of Sox2, cMyc and Oct4, and favourably affect the proliferation potential of BMSCs. The combined effect of these treatments was able to induce and retain the endogenous nuclear expression of stem cell transcription factors in BMSCs over an extended number of in vitro passages. Our results therefore suggest that the transient induction and manipulation of endogenous expression of transcription factors critical for stemness can be achieved by modulating the culture conditions; the benefit of which is to circumvent the need for genetic manipulations. In summary, this study has explored the role of BMSCs in the diseased state of osteoarthritis, by employing transcriptional profiling along with SI. In particular this study pioneered the use of primary cells for generating novel antibodies by SI. We established that somatic cells and BMSCs have a basal level of expression of pluripotency markers. Furthermore, our study indicates that intrinsic signalling mechanisms of BMSCs are intimately linked with extrinsic cues from the microenvironment and that these signals appear to be critical for retaining the expression of genes to maintain cell stemness in long term in vitro culture. This project provides a basis for developing an “artificial niche” required for reversion of commitment and maintenance of BMSC in their uncommitted homeostatic state

A Study of Mental Illness in Pasho in Krishna Sobti’s Memory’s Daughter

Since the second half of the twentieth century, cultural theorists have shown more interest in understanding the interaction between body and culture. This interaction has been studied from the perspective of illness-experience in individuals by Arthur Kleinman and Judith Lorber. Judith Lorber and Lise Jean Moore in Gender and Social construction of Illness advocate illness not merely a bodily event but a social experience –a disturbance in social lives without or without physical dysfunction wherein one feels constraints upon body in pursuing the usual tasks of life. Kleinman in Illness Narrative studies illness as a cultural construct, wherein some bodily conditions are categorized as illness and some are often passed on as normal because what is seen a normal and natural in a culture is based on the shared understanding in that culture.  The present paper aims to explore the role of culture through the lens of illness experience in Pasho in Krishna Sobti’s Memory’s Daughter

Development and randomized controlled trial evaluation of “Safeguard Your Smile” an oral health literacy intervention promoting oral hygiene self-care behavior among Punjabi immigrants

Contexte: Les résultats de plusieurs recherches mettent en évidence dans la population immigrante, une prévalence élevée des maladies bucco-dentaires, une faible accessibilité aux soins bucco-dentaires ainsi qu’un faible niveau de connaissances en matière d’hygiène bucco-dentaire, par rapport aux citoyens nés au Canada. L’amélioration des connaissances et des habiletés en matière d’hygiène bucco-dentaire, constitue un moyen efficace pour réduire les inégalités dans le domaine de la santé bucco-dentaire. La rareté des études, ainsi que la présence de nombreuses lacunes méthodologiques dans le domaine de la littératie en santé bucco-dentaire, notamment au sein de la population immigrante, a conduit à réaliser cette nouvelle étude. Objectifs : Le but de ce projet était de développer et évaluer l’impact d’une intervention sur les compétences en matière de santé bucco-dentaire pour promouvoir des attitudes positives en matière d’hygiène bucco-dentaire chez les immigrants Punjabi. Quatre études séparées ont été menées pour atteindre les quatre objectifs suivant : i) Faire une revue de la littérature pour identifier et synthétiser les données et les lacunes de connaissances actuelles dans le domaine des connaissances et habiletés en matière de santé bucco-dentaire; ii) Développer du matériel éducatif (roman-photo) culturellement et linguistiquement approprié pour les immigrants Punjabi en utilisant une approche communautaire participative; iii) Développer une intervention de littératie sur les compétences en matière de santé bucco-dentaire, fondée théoriquement, pour la promotion des compétences en matière de santé bucco-dentaire chez les immigrants Punjabi; iv) Évaluer l’efficacité de l’intervention de littératie en santé orale sur les compétences en matière de santé bucco-dentaire de promotion des comportements personnels de bonne hygiène bucco-dentaire chez les immigrants Punjabi. Résultats : Les principaux résultats de nos quatre études se répartissent de la façon suivante : 1) Les résultats de la première étude mettent l’emphase sur le besoin de développer de nouveaux outils d’évaluation afin de mesurer les niveaux de connaissance et d’habileté en matière d’hygiène bucco-dentaire et soulignent la rareté des interventions pour la santé bucco-dentaire. De plus, il a été confirmé que des compétences en matière de santé bucco-dentaires limitées sont positivement et significativement liées à de plus faibles connaissances bucco-dentaires et des indicateurs de santé bucco-dentaires plus faibles. En outre, nous avons constaté un déficit d'études sur les interventions parmi les populations vulnérables, en particulier chez les immigrants. 2) Dans la deuxième étude les réunions de groupe de discussion ont révélé quatre thèmes identifiant les perceptions sur les comportements personnels en matière d’hygiène bucco-dentaire chez les immigrants Punjabi : i) manque de compréhension sur les facteurs de risques et sur les connaissances reliées aux comportements personnels en matière d’hygiène bucco-dentaire; ii) manque d’habilités et de routines reliées aux pratiques personnelles d’hygiène bucco-dentaire; iii) manque de compréhension de l’importance de la prévention; et iv) les barrières perçues pour accéder à la santé bucco-dentaire. Les résultats de cette étude ont été utilisés pour développer du matériel éducatif (roman-photo) pour les immigrants Punjabi. 3) La troisième étude a permis de développer une intervention de littératie en santé orale fondée théoriquement sur les comportements personnels d’hygiène bucco-dentaire en utilisant la méthode « Behaviour Change Wheel (BCW) » (la roue du changement de comportement). En utilisant la méthode BCW, nous avons d’abord identifié les barrières et les facilitateurs et les relier aux fonctions d’intervention, des catégories de politiques et techniques par les de changement de comportement spécifique identifié parmi la gamme d'options fournies par la méthode BCW. 4) Dans la quatrième étude une analyse « Linear Mixed Model pour Repeated Measures (LMMRM) » à deux niveaux comparant les groupes d’intervention et contrôle avant et après l’intervention, a montré que les participants qui ont reçu l’intervention « Sauvegarde Ton Sourire » ont eu une amélioration significative de leur routine de brossage et d’utilisation de la soie dentaire, de leurs indices de plaques dentaire et gingivaux, et de leurs compétences en matière de santé bucco-dentaires. Conclusions: L’approche novatrice de la présente étude qui a pour but de développer et d’évaluer une intervention communautaire fondée sur une base théorique, pour la promotion des compétences en matière de santé bucco-dentaire chez les immigrants Punjabi, a abordé son déficit et proposé un modèle d’intervention qui peut être adapté à d’autres communautés ayant un faible niveau de connaissance et de pratique quotidienne en matière d’hygiène bucco-dentaire, afin réduire les inégalités de santé bucco-dentaire. Mots-clés : La littératie en santé orale, comportement personnel en matière d’hygiène bucco-dentaire, intervention, immigrants Punjabi.Background: Research shows that immigrants have higher rates of oral diseases, poorer access to dental care services and lower levels of health literacy than their Canadian-born peers. Recently, oral health literacy has emerged as a potential pathway to reduce oral health disparities. Existent scarcity and methodological shortcomings of studies on oral health literacy interventions particularly among immigrants lent urgency to our present research study. Objectives: The overarching goal of present research study was to develop and evaluate the effectiveness of an oral health literacy intervention aimed to promote positive oral hygiene self-care behavior among Punjabi immigrants. To achieve this goal, we conducted four separate studies having following objectives: i) To conduct a scoping review to identify and synthesize the current evidence and knowledge gaps on the topic of oral health literacy. ii) To develop a culturally and linguistically appropriate educational material (photonovel) for Punjabi immigrants using a community based participatory approach. iii) To develop a theoretically grounded oral health literacy intervention aimed to improve oral hygiene self-care behavior among Punjabi immigrants. iv) To evaluate the effectiveness of the developed oral health literacy intervention aimed to promote positive oral hygiene self-care behavior among Punjabi immigrants. Results: The main findings of our four investigations were: 1) Findings of the first study affirmed a need to develop new assessment tools to capture all dimensions of oral health literacy and highlighted scarcity of oral health literacy interventions among vulnerable populations particularly among immigrants. Also, it affirmed that low oral health literacy is positively and significantly related to poor oral health knowledge, poor oral health behaviour and poor oral health outcomes. 2) In the second study, the focus group meetings revealed four themes identifying following perceptions held by Punjabi immigrants regarding oral hygiene self-care: i) lack of understanding about oral hygiene self-care related knowledge and risk factors; ii) lack of oral hygiene self-care related adequate skills and routine; iii) lack of emphasis on prevention by oral health care providers; and iv) perceived barriers to access dental health. Findings of the focus group discussions were used to develop an educational material (photonovel) for Punjabi immigrants. 3) The third study developed a theoretically grounded oral health literacy intervention aimed to improve oral hygiene self-care behavior by employing “Behaviour Change Wheel” (BCW) method. Using the BCW method, we first identified various barriers and enablers and linked those with specific intervention functions, policy categories and behavior change techniques identified from the range of options provided by the BCW. Six intervention functions (education, training, modeling, restriction, environmental restructuring and enablement) were subsequently mapped to two policy categories (communication and service provision) since they met the APEASE criteria. 4) In the fourth study, linear mixed model analysis for repeated measures comparing the intervention and control groups at pre-and post-intervention reported that participants who received “Safeguard Your Smile” intervention showed significant improvement in their adequately brushing and flossing routine and in their plaque and gingival indices and oral health literacy than control group participants. Conclusions: The novel attempt of the present research study of developing and evaluating a theoretically grounded and community based oral health literacy intervention among Punjabi immigrants has addressed a deficit in this field and proposed a model of oral health literacy intervention that could be adapted among other low oral health literate communities to reduce the oral health disparities

A REVIEW ON THE FIFTH PANDEMIC: CORONAVIRUS

Since the 1918 flu pandemic, the novel human coronavirus outbreak COVID-19 has been the fifth known pandemic. COVID-19 was first identified in Wuhan, China, and later spread across the world. It is an infectious disease caused by the coronavirus 2 (SARS-CoV-2) extreme acute respiratory syndrome virus. The patients exhibit flu-like symptoms, including dry cough, sore throat, high fever, and trouble in breathing. Despite too much affords, there is no appropriate treatment or medication which is a successful COVID-19 therapy. A variety of candidate drugs are being used for the treatment and reviewed. This involves clinically accessible medications that are being repurposed for the treatment of COVID-19, such as chloroquine, hydroxychloroquine, and lopinavir/ritonavir. This review describes the different aspects of corona such as history, origin and spread, its types, life cycle, epidemiology, pathogenesis, diagnosis, treatment, and precautions. This review makes us understand what type of virus is this and how we can take precautions to protect us from this life-threatening virus. There is an immediate need to prepare our young generation to fight against any such catastrophe in the future, if any, of science and technology. There is no reason to worry and to fight this epidemic, careful prevention and control are necessary. This article can help to create public awareness, knowledge, avoiding, handling, and treating COVID-19