Morphological spectrum of vesiculobullous skin lesions: An institutional perspective

Introduction: A vesiculobullous lesion of the skin encompasses a group of dermatological disorders with protean clinicopathological features. They usually occur as a part of the spectrum of various infectious, inflammatory, drug-induced, genetic, and autoimmune disorders. Therefore, accurate diagnosis of these lesions is essential for appropriate management and to reduce the associated morbidity and mortality. The conventional skin punch biopsy is the mainstay in the diagnosis of dermatological diseases, especially when combined with confirmatory tests, such as direct immunofluorescence (DIF). Our study evaluated the clinicopathological spectrum of vesiculobullous lesions.Methods: We studied 150 cases of vesiculobullous lesions at the Department of Histopathology, Liaquat National Hospital and Medical College Karachi, Pakistan. Written and informed consent was taken from the patients followed by skin punch procedure in which three biopsies were obtained, which included one biopsy from the lesion and two peri-lesional biopsies. One peri-lesional biopsy was sent in cryomatrix for DIF studies, whereas the other two were sent in formalin to follow the standard tissue-processing protocol.Results: Our results showed that most patients belonged to the geriatric age group of more than 50 years (44.7%), and 54.7% of the patients were females. Total 74.7% of the patients had generalized lesions, followed by lower limbs (9.3%) and trunk (7.3%) involvement. Most patients were diagnosed with bullous pemphigoid (31.3%), followed by pemphigus vulgaris (27.3%), dermatitis herpetiformis (15.3%), Darier’s disease (14.7%), pemphigus foliaceus (4.7%), epidermolysis bullosa (2%), linear immunoglobulin A dermatosis (2%), paraneoplastic pemphigus (0.7%), and drug reactions (0.7%). DIF studies were applied on 60 cases, out of which complement protein C3c was the most commonly deposited protein (53.3%).Conclusion: Our study emphasized the diagnostic role of skin punch biopsy in the proper evaluation of vesiculobullous skin lesions. Histopathology is the cornerstone diagnostic tool in this regard, with DIF being a useful adjunct

Effect of Virulence Factors on the Photodynamic Inactivation of Cryptococcus neoformans

Opportunistic fungal pathogens may cause an array of superficial infections or serious invasive infections, especially in immunocompromised patients. Cryptococcus neoformans is a pathogen causing cryptococcosis in HIV/AIDS patients, but treatment is limited due to the relative lack of potent antifungal agents. Photodynamic inactivation (PDI) uses the combination of non-toxic dyes called photosensitizers and harmless visible light, which produces singlet oxygen and other reactive oxygen species that produce cell inactivation and death. We report the use of five structurally unrelated photosensitizers (methylene blue, Rose Bengal, selenium derivative of a Nile blue dye, a cationic fullerene and a conjugate between poly-L-lysine and chlorin(e6)) combined with appropriate wavelengths of light to inactivate C. neoformans. Mutants lacking capsule and laccase, and culture conditions that favoured melanin production were used to probe the mechanisms of PDI and the effect of virulence factors. The presence of cell wall, laccase and melanin tended to protect against PDI, but the choice of the appropriate photosensitizers and dosimetry was able to overcome this resistance.Fundação de Amparo à Pesquisa do Estado de São Paulo (2010/13313–9

Topological structure of complex networks and its importance in diffusion

The availability of huge data, due to the tremendous storage capacity of modern computers has allowed the systematic collection, and high processing speed has permitted analysis on that data by researchers on a scale far larger than previously possible. Due to this, complex network formation has been seen and observed in many real and artificial complex systems. As these systems are very large and complex, we cannot get an understanding of these complex systems just by only examining the separate components which constitute these systems. Therefore, modeling the way these components are interconnected in a system is very important for understanding the system as a whole. Further, despite the enormous variation in their components, functions, and sizes, these networks are surprisingly similar in topology, leading to the conjecture that complex systems are governed by the ubiquitous self-organizing principle. In this research, we emphasize on the importance of heterogeneous topological structure of real-world complex networks and its importance in understanding the phenomenon of diffusion in these networks

Ginger ring compounds as an inhibitor of spike binding protein of alpha, beta, gamma and delta variants of SARS-CoV-2: An in-silico study

The available drugs against coronavirus disease 2019 (COVOD-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are limited. This study aimed to identify ginger-derived compounds that might neutralize SARS-CoV-2 and prevent its entry into host cells. Ring compounds of ginger were screened against spike (S) protein of alpha, beta, gamma, and delta variants of SARS-CoV-2. The S protein FASTA sequence was retrieved from Global Initiative on Sharing Avian Influenza Data(GISAID) and converted into “.pdb” format using Open Babel tool. A total of 306 compounds were identified from ginger through food and phyto-databases. Out of those, 38 ring compounds were subjected to docking analysis using CB Dock online program which implies AutoDock Vina for docking. The Vina score was recorded, which reflects the affinity between ligands and receptors. Further, the Protein Ligand Interaction Profiler (PLIP) program for detecting the type of interaction between ligand-receptor was used. SwissADME was used to compute druglikeness parameters and pharmacokinetics characteristics. Furthermore, energy minimization was performed by using Swiss PDB Viewer (SPDBV) and energy after minimization was recorded. Molecular dynamic simulation was performed to find the stability of protein-ligand complex and root-mean-square deviation (RMSD) as well as root-mean-square fluctuation (RMSF) were calculated and recorded by using myPresto v5.0. Our study suggested that 17 out of 38 ring compounds of ginger were very likely to bind the S protein of SARS-CoV-2. Seventeen out of 38 ring compounds showed high affinity of binding with S protein of alpha, beta, gamma, and delta variants of SARS-CoV-2. The RMSD showed the stability of the complex was parallel to the S protein monomer. These computer-aided predictions give an insight into the possibility of ginger ring compounds as potential anti-SARS-CoV-2 worthy of in vitro investigations

Molecular features that could affect APDI effectiveness.

a<p>As the conjugate has 37 primary amino groups, the number of charges depends of pH and microenviroment.</p>b<p>Average extinction coefficient over range 400–700-nm.</p

Effect of laccase enzyme on photodynamic inactivation of <i>C. neoformans</i> ATCC 208820 (laccase positive strain, black squares), and ATCC 208819 (laccase negative strain, open circles).

<p>(A) methylene blue, (B) rose bengal, (C) EtNBSe, (D) BB6, (E) pL-ce6 were used as photosensitizers at 10 µM in PBS for 30 min followed by a wash and illumination with the wavelengths specified in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054387#pone-0054387-t002" target="_blank">Table 2</a>. Data are means and bars are the standard deviation. * P<0.05; ** P<0.01; *** P<0.001 for survival of 208820 vs 208820.</p

Chemical structures of the photosensitizers used in this study.

<p>(A) Methylene blue; (B) Rose Bengal; (C) Selenium Nile blue derivatrive (EtNBSe); (D) Tris-cationic fullerene (BB6); poly-L-lysine chlorin (e6) conjugate (pL-ce6).</p

Confocal microscopy image of <i>C. neoformas</i> KN99α.

<p>Cells were treated with APDI mediated by pL-ce6 (10 µM) and then incubated with FITC-annexin V and PI. Green represents fluorescence of externalized phosphatidylserine that is correlated to the initial steps of apoptosis, and red corresponds to fluorescence of PI (advanced apoptosis/necrosis). We present three pictures of the same field: Transmittance in column A, green and red fluorescence in columns B and C respectively. The first line of figures is the stained samples before APDI (0J/cm²), the second line is following an irradiation of 10J/cm² and the last one was irradiated with fluence of 40J/cm². Scale bars 8µm.</p

Irradiation and fluorescence parameters for each photosensitizer.

<p>Irradiation and fluorescence parameters for each photosensitizer.</p

Protection of <i>C. neoformans</i> against APDI by melanin.

<p><i>C. neoformans</i> ATCC 208820 (laccase positive strain) were grown in a minimal medium with or without L-dopa and subjected to APDI with pL-ce6 (10 µM in PBS for 30 min followed by a wash and illumination with 665-nm). Data are means and bars are the standard deviation. * P<0.05; ** P<0.01; *** P<0.001 for survival of +L-dopa vs no L-dopa.</p