A Clinicopathological and Immunofluorescence study of Lichen Planus

INTRODUCTION : Lichen planus is a papulosquamous disease of the skin and mucous membranes. It is derived from two words, ‘leichen’ in Greek meaning tree moss and ‘planus’ in Latin meaning flat. Lichen planus is worldwide in distribution with a variable incidence. It is considered to be due to cell mediated immune response to an epidermal antigen in genetically predisposed persons. Lichen planus has been found to be associated with certain infections and autoimmune diseases. In its classic presentation, the disease is characterized by pruritic violaceous papules most commonly on the extremities of middle aged adults. It may be accompanied by oral and genital mucosal involvement. Hair and nails may also be affected. Besides the typical lesions, there are many variants of the disease. The course of the disease is unpredictable. It generally persists for a period of several months to years. Sometimes it may follow a chronic relapsing course. The duration varies according to the extent and site of involvement and the morphology of the lesions. Though this condition is mostly self-limiting, sometimes the patient may have considerable discomfort and disability. The lesions may heal with pigmentary changes and scarring. Malignant transformation may occur rarely. Biopsy of fully developed lesions of lichen planus shows characteristic histological changes. Characteristic staining patterns are observed in the immunofluorescence study of the lesions. Treatment options are based on the extent and severity of the disease. Symptomatic treatment is usually sufficient. In severe cutaneous and mucosal lichen planus, various other treatment approaches are useful. Glucocorticoids (topical, intralesional, systemic), cyclosporine, antimalarials, dapsone, thalidomide, azathioprine, phototherapy, doxycycline, interferons have been found to be effective. AIM OF THE STUDY : 1.To find out the clinical profile of lichen planus seen among patients attending the skin OPD. 2.To find out the dermatological and systemic associations and complications if any. 3.To correlate the clinical and histopathological features of various types of LP. 4.To know the immunofluorescence patterns of LP. MATERIALS AND METHODS : The material for this study was from the patients attending the skin OPD, Government Rajaji Hospital, Madurai Medical College, Madurai during the period from July 2008 to July 2009. Inclusion criteria : Patients diagnosed clinically as lichen planus during the study period. Exclusion criteria : Patients who did not give consent for biopsy were not subjected to biopsy procedure but were included in the study of the clinical profile. A total of 90 patients were clinically diagnosed as lichen planus during this period and were taken for the study. A detailed clinical history including duration, site of onset, symptoms, drug history, family history were elicited. A complete general examination, systemic examination and dermatological examination were made. Digital photographs were taken. The morphology and distribution of skin lesions, presence of any other associated diseases were noted. Concomitant affection of mucosa, hair, nails, palms, soles, genital involvement was meticulously p recorded. Laboratory investigations like urine examination, blood sugar, urea, creatinine, liver function tests, anti HCV antibody, blood VDRL and complete hemogram were done. Skin biopsy was done in 50 patients who gave informed consent. After thorough cleaning of the part to be biopsied with spirit, 2% lignocaine was infiltrated into the area and a bit of the lesional skin was removed by punch biopsy. The specimen were preserved in 10% formalin and submitted for histopathological examination to the department of Pathology, Madurai Medical College. Out of the 50 patients in whom histopathological examination was done, direct immunofluorescence study could be done in only 20 patients due to financial constraints. The lesional skin was biopsied and specimen preserved in Michel’s medium and sent to the department of Skin and STD, Kasturba hospital, Manipal. SUMMARY : Incidence: Lichen planus constituted 0.16 percent of the total patients diagnosed during the period of study. Age: 51% of patients were between 31-50 years of age. Childhood LP accounted for about 9% of cases. Sex: No sexual predilection was seen. Familial involvement& seasonal variation: There was no family history and seasonal variation was not seen. Morphology and distribution of lesions: Papules were present in 79% and plaques were present in 14% of the cases . Initial site of onset was limbs in 63% , trunk in21% ,face in 8%, oral mucosa in 6% and genital mucosa in 2% .Oral mucosa was involved in 21% .Nail involvement was noted in17%.Palmoplantar involvement was present in 20%.Koebner’s phenomenon was seen in 33%. Clinical patterns: Classical LP was the commonest seen in 60 cases followed by hypertrophic LP seen in 10 cases. A linear pattern was seen in 5 cases. A zosteriform pattern in trunk was present in one case of linear LP of the limb. 3 cases had LP pigmentosus ,4 patients had eruptive LP,1 had actinic LP and 2 patients had follicular LP. 1 patient had features of LE/LP overlap.Isolated oral LP and annular LP were present in 2 cases each. Histopathology: Histopathological features were consistent with classical LP in 30 cases , hypertrophic LP in 9 cases, Follicular LP in 2 , LP pigmentosus in 3, actinic LP in 1,oral LP in 2, LE/LP overlap in 1,drug induced LP in 2. Features of squamous cell carcinoma was present in the warty growth from a case of hypertrophic LP . Immunofluorescence: DIF study done in 20 patients showed ragged fibrinogen deposits in basement membrane zone in all the patients. Colloid bodies were seen in 60%. Linear IgG, C3 at the BMZ with shaggy fibrinogen was seen in the LE/LP overlap syndrome. Linear IgG,C3 at the BMZ with shaggy fibrinogen was also present in three cases of classical LP. Associations: In this study, the diseases which were found to be associated were diabetes mellitus, hypertension, hypothyroidism, vitiligo & alopecia areata .Interesting presentation of lichen planus in a case of albinism was seen. Malignant change: A case of hypertrophic LP developed squamous cell carcinoma. CONCLUSION : 1.The incidence of Lichen planus in this study was 0.16% . 2. Most of the patients were in 4th and 5th decade. 3. Classical type was the commonest followed by hypertrophic type & linear variant next in frequency. 4. Limbs were the most frequent initial site of onset. 5. Concomitant mucosal, genital, nail and palmoplantar involvement was common. 6. There was a complete correlation be tween clinical types and histo pathological features in all the 50 patients biopsied. 7. The characteristic findings of ragged fibrin at BMZ and colloid bodies with IgM and C 3 & to a lesser extent with other classes of immunoglobulins were observed in the immunofluorescence study. 8. A case of zosteriform lichen planus coexisting with linear LP was present. 9. Association of other immune mediated diseases was noted. 10. Malignant change was observed in a case of hypertrophic lichen planus. 11.Interesting presentation of lichen planus in a case of albinism was noted

A Dynamical Analysis of a Mathematical Model on Type-2 Diabetic From Obestiy

The aim of this research is to construct a model for type-2 diabeticfrom obesity using parameters based on the female population in India.We have introduced two control variables as diet with physicalactivity and medication. The positive endemic equilibrium is obtained.The local and global stability of the model are analyzed withsome specific conditions. Numerical simulations are carried out to exhibitthe flow of variables with controls. Our study mainly highlightsthe awareness of metabolic risk by healthy diet, physical activitiesand medications

5'PPP-RNA induced RIG-I activation inhibits drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza virus replication

<p>Abstract</p> <p>Background</p> <p>Emergence of drug-resistant strains of influenza viruses, including avian H5N1 with pandemic potential, 1918 and 2009 A/H1N1 pandemic viruses to currently used antiviral agents, neuraminidase inhibitors and M2 Ion channel blockers, underscores the importance of developing novel antiviral strategies. Activation of innate immune pathogen sensor Retinoic Acid Inducible Gene-I (RIG-I) has recently been shown to induce antiviral state.</p> <p>Results</p> <p>In the present investigation, using real time RT-PCR, immunofluorescence, immunoblot, and plaque assay we show that 5'PPP-containing single stranded RNA (5'PPP-RNA), a ligand for the intracytoplasmic RNA sensor, RIG-I can be used as a prophylactic agent against known drug-resistant avian H5N1 and pandemic influenza viruses. 5'PPP-RNA treatment of human lung epithelial cells inhibited replication of drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza viruses in a RIG-I and type 1 interferon dependant manner. Additionally, 5'PPP-RNA treatment also inhibited 2009 H1N1 viral replication <it>in vivo </it>in mice.</p> <p>Conclusions</p> <p>Our findings suggest that 5'PPP-RNA mediated activation of RIG-I can suppress replication of influenza viruses irrespective of their genetic make-up, pathogenicity, and drug-sensitivity status.</p

Daksha: On Alert for High Energy Transients

We present Daksha, a proposed high energy transients mission for the study of electromagnetic counterparts of gravitational wave sources, and gamma ray bursts. Daksha will comprise of two satellites in low earth equatorial orbits, on opposite sides of earth. Each satellite will carry three types of detectors to cover the entire sky in an energy range from 1 keV to >1 MeV. Any transients detected on-board will be announced publicly within minutes of discovery. All photon data will be downloaded in ground station passes to obtain source positions, spectra, and light curves. In addition, Daksha will address a wide range of science cases including monitoring X-ray pulsars, studies of magnetars, solar flares, searches for fast radio burst counterparts, routine monitoring of bright persistent high energy sources, terrestrial gamma-ray flashes, and probing primordial black hole abundances through lensing. In this paper, we discuss the technical capabilities of Daksha, while the detailed science case is discussed in a separate paper.Comment: 9 pages, 3 figures, 1 table. Additional information about the mission is available at https://www.dakshasat.in

Science with the Daksha High Energy Transients Mission

We present the science case for the proposed Daksha high energy transients mission. Daksha will comprise of two satellites covering the entire sky from 1~keV to $>1$~MeV. The primary objectives of the mission are to discover and characterize electromagnetic counterparts to gravitational wave source; and to study Gamma Ray Bursts (GRBs). Daksha is a versatile all-sky monitor that can address a wide variety of science cases. With its broadband spectral response, high sensitivity, and continuous all-sky coverage, it will discover fainter and rarer sources than any other existing or proposed mission. Daksha can make key strides in GRB research with polarization studies, prompt soft spectroscopy, and fine time-resolved spectral studies. Daksha will provide continuous monitoring of X-ray pulsars. It will detect magnetar outbursts and high energy counterparts to Fast Radio Bursts. Using Earth occultation to measure source fluxes, the two satellites together will obtain daily flux measurements of bright hard X-ray sources including active galactic nuclei, X-ray binaries, and slow transients like Novae. Correlation studies between the two satellites can be used to probe primordial black holes through lensing. Daksha will have a set of detectors continuously pointing towards the Sun, providing excellent hard X-ray monitoring data. Closer to home, the high sensitivity and time resolution of Daksha can be leveraged for the characterization of Terrestrial Gamma-ray Flashes.Comment: 19 pages, 7 figures. Submitted to ApJ. More details about the mission at https://www.dakshasat.in

MoNuSAC2020:A Multi-Organ Nuclei Segmentation and Classification Challenge

Detecting various types of cells in and around the tumor matrix holds a special significance in characterizing the tumor micro-environment for cancer prognostication and research. Automating the tasks of detecting, segmenting, and classifying nuclei can free up the pathologists' time for higher value tasks and reduce errors due to fatigue and subjectivity. To encourage the computer vision research community to develop and test algorithms for these tasks, we prepared a large and diverse dataset of nucleus boundary annotations and class labels. The dataset has over 46,000 nuclei from 37 hospitals, 71 patients, four organs, and four nucleus types. We also organized a challenge around this dataset as a satellite event at the International Symposium on Biomedical Imaging (ISBI) in April 2020. The challenge saw a wide participation from across the world, and the top methods were able to match inter-human concordance for the challenge metric. In this paper, we summarize the dataset and the key findings of the challenge, including the commonalities and differences between the methods developed by various participants. We have released the MoNuSAC2020 dataset to the public

Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990-2019, for 204 countries and territories: the Global Burden of Diseases Study 2019

Background: The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. Methods: To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0·03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1·0). Findings: In 2019, there were 36·8 million (95% uncertainty interval [UI] 35·1–38·9) people living with HIV worldwide. There were 0·84 males (95% UI 0·78–0·91) per female living with HIV in 2019, 0·99 male infections (0·91–1·10) for every female infection, and 1·02 male deaths (0·95–1·10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28·52% decrease in incident cases, 95% UI 19·58–35·43, and a 39·66% decrease in deaths, 36·49–42·36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0·05 (95% UI 0·05–0·06) and the global incidence-to-mortality ratio was 1·94 (1·76–2·12). No regions met suggested thresholds for progress. Interpretation: Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics. Funding: The Bill & Melinda Gates Foundation, the National Institute of Mental Health of the US National Institutes of Health (NIH), and the National Institute on Aging of the NIH

Spatial, temporal, and demographic patterns in prevalence of chewing tobacco use in 204 countries and territories, 1990-2019 : a systematic analysis from the Global Burden of Disease Study 2019

Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Findings In 2019, 273 center dot 9 million (95% uncertainty interval 258 center dot 5 to 290 center dot 9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 center dot 72% (4 center dot 46 to 5 center dot 01). 228 center dot 2 million (213 center dot 6 to 244 center dot 7; 83 center dot 29% [82 center dot 15 to 84 center dot 42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global agestandardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 center dot 21% [-1 center dot 26 to -1 center dot 16]), similar progress was not observed for chewing tobacco (0 center dot 46% [0 center dot 13 to 0 center dot 79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 center dot 94% [-1 center dot 72 to -0 center dot 14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Summary Background Chewing tobacco and other types of smokeless tobacco use have had less attention from the global health community than smoked tobacco use. However, the practice is popular in many parts of the world and has been linked to several adverse health outcomes. Understanding trends in prevalence with age, over time, and by location and sex is important for policy setting and in relation to monitoring and assessing commitment to the WHO Framework Convention on Tobacco Control. Methods We estimated prevalence of chewing tobacco use as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 using a modelling strategy that used information on multiple types of smokeless tobacco products. We generated a time series of prevalence of chewing tobacco use among individuals aged 15 years and older from 1990 to 2019 in 204 countries and territories, including age-sex specific estimates. We also compared these trends to those of smoked tobacco over the same time period. Findings In 2019, 273 & middot;9 million (95% uncertainty interval 258 & middot;5 to 290 & middot;9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 & middot;72% (4 & middot;46 to 5 & middot;01). 228 & middot;2 million (213 & middot;6 to 244 & middot;7; 83 & middot;29% [82 & middot;15 to 84 & middot;42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global age standardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 & middot;21% [-1 & middot;26 to -1 & middot;16]), similar progress was not observed for chewing tobacco (0 & middot;46% [0 & middot;13 to 0 & middot;79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 & middot;94% [-1 & middot;72 to -0 & middot;14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Copyright (c) 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe