Modelling and analysis of the complement system signalling pathways: roles of C3, C5a and pro-inflammatory cytokines in SARS-CoV-2 infection.

The complement system is an essential part of innate immunity. It is activated by invading pathogens causing inflammation, opsonization, and lysis via complement anaphylatoxins, complement opsonin's and membrane attack complex (MAC), respectively. However, in SARS-CoV-2 infection overactivation of complement system is causing cytokine storm leading to multiple organs damage. In this study, the René Thomas kinetic logic approach was used for the development of biological regulatory network (BRN) to model SARS-CoV-2 mediated complement system signalling pathways. Betweenness centrality analysis in cytoscape was adopted for the selection of the most biologically plausible states in state graph. Among the model results, in strongly connected components (SCCs) pro-inflammatory cytokines (PICyts) oscillatory behaviour between recurrent generation and downregulation was found as the main feature of SARS-CoV-2 infection. Diversion of trajectories from the SCCs leading toward hyper-inflammatory response was found in agreement with in vivo studies that overactive innate immunity response caused PICyts storm during SARS-CoV-2 infection. The complex of negative regulators FI, CR1 and DAF in the inhibition of complement peptide (C5a) and PICyts was found desirable to increase immune responses. In modelling role of MAC and PICyts in lowering of SARS-CoV-2 titre was found coherent with experimental studies. Intervention in upregulation of C5a and PICyts by C3 was found helpful in back-and-forth variation of signalling pattern linked with the levels of PICyts. Moreover, intervention in upregulation of PICyts by C5a was found productive in downregulation of all activating factors in the normal SCCs. However, the computational model predictions require experimental studies to be validated by exploring the activation role of C3 and C5a which could change levels of PICyts at various phases of SARS-CoV-2 infection.

Development of cavitary lung disease as a long-term complication of coronavirus disease 2019 in a young previously healthy patient: a case report.

BACKGROUND: Cavities are frequent manifestations of a wide variety of pathological processes involving the lung. There has been a growing body of evidence of coronavirus disease 2019 leading to a cavitary pulmonary disease. CASE PRESENTATION: A healthy 29-year-old Filipino male presented to the hospital a couple of months after convalescence from coronavirus disease 2019 with severe pleuritic chest pain, fever, chills, and shortness of breath, and was found to have a cavitary lung lesion on chest computed tomography. While conservative management alone failed to improve the patient's condition, he ultimately underwent left lung video-assisted thoracoscopic surgery decortication. Even though the surgical pathology revealed only necrosis with dense acute inflammation and granulation tissue with no microorganisms, he gradually improved with medical therapy adjunct with surgical therapy. CONCLUSION: Documented cases of cavitary lung disease secondary to coronavirus disease 2019 have been mostly reported in the acute or subacute phase of the infection. However, clinicians should recognize this entity as a late complication of coronavirus disease 2019, even in previously healthy individuals.

Underlying Conditions and Clinical Spectrum of Chronic Pulmonary Aspergillosis (CPA): An Experience from a Tertiary Care Hospital in Karachi, Pakistan.

The incidence of chronic pulmonary aspergillosis (CPA) is especially increasing in high tuberculosis (TB) burden countries. Despite a high estimated CPA burden in Pakistan, actual data on CPA are not available. The aim of the current study is to determine the underlying conditions and clinical spectrum of CPA at a tertiary care hospital in Karachi, Pakistan. This is a retrospective chart review study in patients admitted with CPA from January 2012 to December 2017. A total of 67 patients were identified during the study period. Mean age of CPA patients was 45.9 ± 15 years, 44 (65.7%) were male and 19 (28.4%) had diabetes. The most common type of CPA was simple aspergilloma (49.2%) followed by chronic cavitary pulmonary aspergillosis (CCPA) (44.7%). TB was the underlying cause of CPA in 58 (86.6%) patients followed by bronchiectasis caused by allergic bronchopulmonary aspergillosis (ABPA) 8 (11.9%). Aspergillus flavus was identified in 17 (47.2%), followed by A. fumigatus in 13 (36.1%) CPA patients. Isolation of multiple Aspergillus species was found in 10 (25.6%) patients. Itraconazole was given in 27 (40.3%) patients and a combination therapy of itraconazole and surgery was given in 21 (31.34%) patients. We found aspergilloma and CCPA as the most prevalent forms of CPA in our setting. Further large prospective studies using Aspergillus specific immunoglobulin G (IgG) antibodies testing are required for better understanding of CPA in Pakistan.

Correction: Buoyancy effects in stagnation-point flow of Maxwell fluid utilizing non-Fourier heat flux approach.

[This corrects the article DOI: 10.1371/journal.pone.0192685.].

Buoyancy effects in stagnation-point flow of Maxwell fluid utilizing non-Fourier heat flux approach.

Here we utilize a non-Fourier approach to model buoyancy aiding or opposing flow of Maxwell fluid in the region of stagnation-point towards a vertical stretchable surface. Flow field is permeated by uniform transverse magnetic field. Two different heating processes namely (i) prescribed surface temperature (PST) and (ii) constant wall temperature (CWT) are analyzed. Through suitable transformations, the similarity equations are formed which are treated numerically for a broad range of magnetic interaction parameter. The obtained solutions are compared with available articles under limiting situations and such comparisons appear convincing. The structure of boundary layer depends on a parameter measuring the ratio of free stream velocity to the stretching sheet velocity. The momentum transport via stretching boundary is opposed by both fluid relaxation time and magnetic interaction parameter. Thermal boundary layer expands as the effects of transverse magnetic field and thermal relaxation time are amplified. A reduction in heat penetration depth is anticipated for increasing values of thermal relaxation time. The variation in wall slope of temperature with increasing thermal relaxation time appears similar at any assigned value of Prandtl number. A comparative study of aiding and opposition flow situations is presented and deliberated.

Electronic cigarettes use and perception amongst medical students: a cross sectional survey from Sindh, Pakistan.

OBJECTIVE: The manufacturers of electronic cigarettes (e-cigarettes) are actively marketing their product through electronic and social media. Undergraduate medical students are expected to have better knowledge and awareness as they directly interact with patients in their training, The purpose of this study is therefore, to determine knowledge, use and perception regarding e-cigarettes among medical students from Sindh, Pakistan. RESULTS: A cross-sectional study was conducted between 1st July and 30th September 2016 at five different medical colleges situated in the second largest province of Sindh, Pakistan. The data was collected through a structured, self-administered questionnaire. Of the 500 students, the mean age was 21.5 ± 1.7 years and 58% were females. Over (65.6%) students were aware of e-cigarettes, 31 (6.2%) reported having used e-cigarettes, of whom 6 (1.2%) self-reported daily use. Users of conventional tobacco products were significantly more likely to have heard of e-cigarettes (87.6% vs 51.6%, p < 0.001) and having used them (13.9% vs 1.3%, p < 0.001). On multivariable logistic regression analysis we found a strong association of e-cigarette use with consumption of conventional cigarettes [OR: 10.6, 95% CI 3.6-30.8, p < 0.001], use of smokeless tobacco products [OR: 7.9, 95% CI 2.7-23.4, p < 0.001] however a weak association was observed for Shisha use [OR: 3.05, 95% CI 0.9-9.6, p = 0.05].

Nonlinear radiation heat transfer effects in the natural convective boundary layer flow of nanofluid past a vertical plate: a numerical study.

The problem of natural convective boundary layer flow of nanofluid past a vertical plate is discussed in the presence of nonlinear radiative heat flux. The effects of magnetic field, Joule heating and viscous dissipation are also taken into consideration. The governing partial differential equations are transformed into a system of coupled nonlinear ordinary differential equations via similarity transformations and then solved numerically using the Runge-Kutta fourth-fifth order method with shooting technique. The results reveal an existence of point of inflection for the temperature distribution for sufficiently large wall to ambient temperature ratio. Temperature and thermal boundary layer thickness increase as Brownian motion and thermophoretic effects intensify. Moreover temperature increases and heat transfer from the plate decreases with an increase in the radiation parameter.