Autoimmune bullous diseases:insights into diagnosis and disease management

Autoimmune blistering diseases (AIBDs) are a group of rare and chronic skin and mucosal disorders caused by autoantibodies targeted against structural proteins of the desmosomal and hemidesmosomal plaques. MMP is the appropriate term used for pemphigoid diseases with predominant mucosal involvement. One or more mucosal sites can be affected and new lesions on other mucosal sites can develop later during the disease course. Therefore, it is important that patients are monitored for the development of new symptoms. The diagnosis is made based on a biopsy for direct immunofluorescence microscopy combined with serum for indirect immunofluorescence microscopy. Demonstration of antibodies against laminin 332 is important given the possible association between laminin 332 and a malignancy. A multidisciplinary approach in specialized centers is essential in the treatment and monitoring of MMP. In general, the management of AIBDs is based on the use of unspecific systemic immunosuppressive and immunomodulatory therapy with varying results in effectiveness. The introduction of rituximab led to a revolutionary step in the treatment of pemphigus vulgaris. In addition, the administration of additional maintenance infusions of rituximab at month 6 and 12 seems to be beneficial in preventing relapses. In addition to the clinical effectiveness, rituximab showed improvement in the quality of life of patients with pemphigoid and pemphigus. Furthermore, nomacopan, a dual inhibitor of complement C5 and leukotriene B4 (LTB4), appears to be safe and effective for the treatment of bullous and nonbulleus pemphigoid. In contrast, Apremilast, a PDE4 inhibitor, seems not to be effective in the treatment of bullous and nobulleus pemphigoid

Mucous membrane pemphigoid

Mucous membrane pemphigoid (MMP) is the subgroup of pemphigoid which predominantly affects mucous membranes. Scarring and limited skin involvement are possible. Several subtypes are classified based on clinical symptoms and target antigens, such as ocular mucous membrane pemphigoid, localized vulvar pemphigoid (LVP) and anti-laminin 332 MMP (anti-LN-332 MMP). Autoantibodies are directed against various structural proteins in the epidermal basement membrane zone (EBMZ), with the 180-kD antigen (BP180) as the main target antigen. Other antigens, such as BP230, the heterotrimeric glycoprotein laminin 332 and A6B4 integrin can also be targeted by autoantibodies. Various mucosa can be affected and are histologically characterized as nonkeratinized stratified squamous epithelium. The clinically heterogeneous disease is characterized by erosions and blistering of the oral mucosa (85%), conjunctiva (30-60%), and less frequently, the nasal mucosa (20-40%), esophagus (5-15%), pharyneal (20%) or laryngeal mucosa (5-10%) and anogenital mucosa (25%). Clinical severity is highly variable in the different subtypes of MMP. Previously, the term cicatricial pemphigoid was used for MMP. Progressive scar formation is a severe complication in ocular MMP and anti-LN-332 MMP, but scarring does not occur in all patients with MMP. Patient and doctors delay is frequently seen in MMP because of the heterogeneous clinical presentation and unfamiliarity among clinicians. For an accurate diagnosis, direct immunofluorescence microscopy (DIF) and detection of circulating autoantibodies in serum is essential. The multidisciplinary management and prognosis of MMP depends on the severity and extent of the disease and involves topical corticosteroids and immunomodulatory and immunosuppressive drugs.</p

Oil Price Shocks and Stock Market Performance in Emerging Economies: Some Evidence using FAVAR Models

This paper examines the response of real stock prices to oil price shocks for four selected emerging economies over the period January 1991–March 2011. To overcome the problem of omitted information in small-scale vector autoregression (VAR) models, we utilize the factor augmented vector autoregressive (FAVAR) approach proposed by Bernanke et al. (2005). Accordingly, we follow Stock and Watson (2002b) and extract two factors which are significantly related with a large set of world-level and country-specific macroeconomic variables. We use the extracted factors as regressors in recursive VARs to assess the response of stock prices to oil price shocks. Our results suggest that the response of stock prices to oil price shocks is quite persistent and precise, but asymmetric across all the four economies. Specifically, we observe that stock prices in Brazil and India respond negatively to oil price shocks, whereas the response of stock prices to oil price shocks in China is positive. We also observe that stock prices in Russia initially respond positively, however, the response becomes negative after four months. The impulse-response results indicate that the impact of oil price shocks on stock prices is smaller for China than that of for remaining three countries. Overall, our results suggest that the use of FAVAR approach allows us to obtained more coherent evidence on the effects of oil price shocks on stock prices by obtaining relatively more precise responses and by increasing the understanding of such shocks from the theoretical point of view

Novel codynamics of the HIV-1/HTLV-Ⅰ model involving humoral immune response and cellular outbreak: A new approach to probability density functions and fractional operators

Both human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type Ⅰ (HTLV-Ⅰ) are retroviruses that afflict CD4 T cells. In this article, the codynamics of within-host HIV-1 and HTLV-Ⅰ are presented via piecewise fractional differential equations by employing a stochastic system with an influential strategy for biological research. It is demonstrated that the scheme is mathematically and biologically feasible by illustrating that the framework has positive and bounded global findings. The necessary requirements are deduced, ensuring the virus's extinction. In addition, the structure is evaluated for the occurrence of an ergodic stationary distribution and sufficient requirements are developed. A deterministic-stochastic mechanism for simulation studies is constructed and executed in MATLAB to reveal the model's long-term behavior. Utilizing rigorous analysis, we predict that the aforesaid model is an improvement of the existing virus-to-cell and cell-to-cell interactions by investigating an assortment of behaviour patterns that include cross-over to unpredictability processes. Besides that, the piecewise differential formulations, which can be consolidated with integer-order, Caputo, Caputo-Fabrizio, Atangana-Baleanu and stochastic processes, have been declared to be exciting opportunities for researchers in a spectrum of disciplines by enabling them to incorporate distinctive features in various temporal intervals. As a result, by applying these formulations to difficult problems, researchers can achieve improved consequences in reporting realities with white noise. White noise in fractional HIV-1/HTLV-Ⅰ codynamics plays an extremely important function in preventing the proliferation of an outbreak when the proposed flow is constant and disease extermination is directly proportional to the magnitude of the white noise

Insights into clinical and diagnostic findings as well as treatment responses in patients with mucous membrane pemphigoid:A retrospective cohort study

Background: The variable clinical severity of mucous membrane pemphigoid (MMP) often leads to diagnostic and therapeutic delays. Objective: To describe the characteristics of a large cohort of patients with MMP. Methods: A retrospective review of clinical and diagnostic characteristics as well as treatment responses in 145 patients with MMP. Results: Monosite involvement was seen in 41.4% and multisite involvement in 58.6% of the patients. The oral mucosa was affected in 86.9% of the patients, followed by the ocular mucosa (30.3%), skin (26.2%), genital mucosa (25.5%), nasal mucosa (23.4%), and pharyngeal and/or laryngeal mucosa (17.2%). Ocular disease developed during the disease course in 41.7% of patients with initially other mucosal site involvement. The malignancy rate was significantly higher in patients with autoantibodies against laminin-332 than in patients with MMP without laminin-332 autoantibodies (35.3% vs 10.9%, respectively; P = .007). Systemic immunosuppressive or immunomodulatory therapy was administered to 77.1% of the patients, mainly to patients with multisite (P Limitations: Retrospective design. Conclusion: Patients with MMP present with a heterogeneous clinical presentation, and new symptoms may develop during the disease course. Cancer screening should be considered for patients with MMP and, in particular, for those with autoantibodies against laminin-332

Threshold Based Best Custodian Routing Protocol for Delay Tolerant Network

Delay Tolerant Network (DTN) is a kind of network in which the source may not be able to establish the stable and uninterrupted path to destination due to network partitioning, dynamic topology change and frequent disconnections. In order to dealt disruption and disconnections a store, carry and forward paradigm is used in which node stores the incoming messages in its buffer, carries it while moving and forward when comes within the transmission range of other nodes. Message forwarding contributes and important role in increasing its delivery. For instance, probabilistic routing protocol forwards message to a node having high probability value to meet message destination. These protocols cannot handle a situation in which the node continually transmits messages even the probability difference is very small. In this paper, we have proposed a routing protocol known as Threshold Based best custodian Routing Protocol (TBbcRP) for delay tolerant network. We have proposed a threshold-based method to compute the quality value which is the ability of node to carry message. A self-learning mechanism has been used to remove the delivered messages from the network. Moreover, a buffer aware mechanism has been used that make sure availability of buffer space at receiver before message transmission. We have compared the performance of TBbcRP with Epidemic, PRoPHET and Delegated Forwarding. The proposed TBbcRP outperforms in terms of maximizing the delivery probability, reducing number of transmissions and message drop

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Oral Lesions in Autoimmune Bullous Diseases:An Overview of Clinical Characteristics and Diagnostic Algorithm

Autoimmune bullous diseases are a group of chronic inflammatory disorders caused by autoantibodies targeted against structural proteins of the desmosomal and hemidesmosomal plaques in the skin and mucosa, leading to intra-epithelial or subepithelial blistering. The oral mucosa is frequently affected in these diseases, in particular, in mucous membrane pemphigoid, pemphigus vulgaris, and paraneoplastic pemphigus. The clinical symptoms are heterogeneous and may present with erythema, blisters, erosions, and ulcers localized anywhere on the oral mucosa, and lead to severe complaints for the patients including pain, dysphagia, and foetor. Therefore, a quick and proper diagnosis with adequate treatment is needed. Clinical presentations of autoimmune bullous diseases often overlap and diagnosis cannot be made based on clinical features alone. Immunodiagnostic tests are of great importance in differentiating between the different diseases. Direct immunofluorescence microscopy shows depositions of autoantibodies along the epithelial basement membrane zone in mucous membrane pemphigoid subtypes, or depositions on the epithelial cell surface in pemphigus variants. Additional immunoserological tests are useful to discriminate between the different subtypes of pemphigoid, and are essential to differentiate between pemphigus and paraneoplastic pemphigus. This review gives an overview of the clinical characteristics of oral lesions and the diagnostic procedures in autoimmune blistering diseases, and provides a diagnostic algorithm for daily practice.</p