The Global Hidradenitis Suppurativa Atlas (GHiSA) methodology: Combining global proportions in a pooled analysis

Introduction: Data concerning the global burden of Hidradenitis Suppurativa (HS) are limited. Reported prevalence estimates vary between 0.0003% and 4.1%, and data from various geographical regions are still to be collected. Previously reported prevalence rates have been limited by the methodological approach and source of data. This has resulted in great heterogeneity as prevalence data from physician-diagnosed cases poorly match those of self-reported apparent HS disease. Methods: The Global Hidradenitis Suppurativa Atlas (GHiSA) introduces an innovative approach to determine the global prevalence of HS. This approach involves using a previously validated questionnaire to screen apparently healthy adults accompanying a patient to a non-dermatological outpatient clinic visit in a hospital. The screening questionnaire (i.e., the index test) is combined with a subsequent physician-based in-person validation (i.e., the reference standard) of the participants who screen positive. Ten percent of the screen-negative participants are also clinically assessed to verify the diagnostic precision of the test. The local prevalence (pi) will be estimated from each country that submits the number of patients who are HS positive according to the index test and clinical examination (n), and the corresponding total number of observations (N). Conclusion: The GHiSA Global Prevalence studies are currently running simultaneously in 58 countries across six continents (Africa, Europe, Australia, North America, South America, and Asia). The goal of the combined global proportion is the generation of a single summary (i.e., proportional meta-analysis), which will be done after a logit transformation, and synthesized using a random-effects model. The novel standardization of the Global Prevalence studies conducted through GHiSA enables direct international comparisons, which were previously not possible due to substantial heterogeneity in past HS prevalence studies

Photocurrent simulation in an n-p-n-p silicon multilayer solar cell

In this work, we simulate and optimize the photocurrent densities in a model of an n-p-n-p type thin film multilayer silicon solar cell for space applications. The incident light penetrates the cell perpendicularly to the junctions. The electrodes tailored inside the structure connect the n-layers together and the p-layers together. The equations giving the photocurrent density produced in each abscissa of the structure was developed. We used Matlab software to simulate and optimize the different parameters of the model. The results of simulation show that the optimized n-p-n-p silicon multilayer solar cell could deliver a photocurrent density of more than 46 mA/cm2 under Air Mass 0 (AM0) solar spectrum (solar constant of 1.36 KW/cm2) and that the photocurrent density produced by the n-p-n-p multilayer silicon solar cell is at least 10% higher than the photocurrent density produced by the simple n-p junction solar cell. We also show that the most important components of the total photocurrent densities (94%) is due to the minority carrier collection which happens on both side of the three space charge regions tailored inside the cell

The P2X7 Receptor Stimulates IL-6 Release from Pancreatic Stellate Cells and Tocilizumab Prevents Activation of STAT3 in Pancreatic Cancer Cells

Pancreatic stellate cells (PSCs) are important pancreatic fibrogenic cells that interact with pancreatic cancer cells to promote the progression of pancreatic ductal adenocarcinoma (PDAC). In the tumor microenvironment (TME), several factors such as cytokines and nucleotides contribute to this interplay. Our aim was to investigate whether there is an interaction between IL-6 and nucleotide signaling, in particular, that mediated by the ATP-sensing P2X7 receptor (P2X7R). Using human cell lines of PSCs and cancer cells, as well as primary PSCs from mice, we show that ATP is released from both PSCs and cancer cells in response to mechanical and metabolic cues that may occur in the TME, and thus activate the P2X7R. Functional studies using P2X7R agonists and inhibitors show that the receptor is involved in PSC proliferation, collagen secretion and IL-6 secretion and it promotes cancer cell migration in a human PSC-cancer cell co-culture. Moreover, conditioned media from P2X7R-stimulated PSCs activated the JAK/STAT3 signaling pathway in cancer cells. The monoclonal antibody inhibiting the IL-6 receptor, Tocilizumab, inhibited this signaling. In conclusion, we show an important mechanism between PSC-cancer cell interaction involving ATP and IL-6, activating P2X7 and IL-6 receptors, respectively, both potential therapeutic targets in PDAC

Radiative heat transfer on the peristaltic flow of an electrically conducting nanofluid through wavy walls of a tapered channel

Present analysis deals with the characteristics of radiative heat on the peristaltic flow of nanofluid through wavy walls of a tapered channel. Peristaltic flows within the pumping process arise in the region having lower to higher pressure region. Assumption of velocity slip along with the convective boundary condition energizes the thermal system as well as the flow phenomena. However, the combined effect of Brownian motion and thermophorsis due to the cross-diffusion effect affects the flow properties. One of the significant applications of the flow is that the blood pumping in the human body. It acts as a vehicle through the liquid that past through the wavy channels walls contacting liquids expands in its length due to the dynamical rush. However, solution of the transformed governing flow phenomena is obtained by employing approximate analytical technique known as Variation Parameter Method (VPM). The characteristics of the parameters involved in the system are presented via graphs. Present outcome warrants that, the significance of magnetic strength and flow through the permeable medium may favours to enhance the pumping procedure as the pressure gradient lower down in the non-Darcy medium found to be one of the important observations. Further, significant enhancement in the fluid temperature and concentration profile is exhibited due to the consideration of the convective conditions i.e. the augmentation in the thermal and solutalBiot numbers respectively

Cytotoxic and antiviral activities of the essential oils from Tunisian Fern, Osmunda regalis

This study was undertaken to assess the in vitro cytotoxic and antiviral activities of the essential oil (EO) from Tunisian fern, Osmunda regalis. The essential oil was obtained by hydrodistillation and its chemical composition was determined by gas chromatography and mass spectrometry (GC-FID and GC–MS) analyses that allowed detecting 85.35% of the components. The main compounds were hexahydrofarnesyl acetone (11.82%), 2,4-di-t-butylphenol (6.80%), and phytol (6.46%). Cytotoxicity of the essential oil was assessed on HEp-2 cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Antiviral activity was also evaluated in vitro against Coxsackievirus B4 (CV-B4), an enterovirus implicated in a variety of diseases such as myocarditis, type 1 diabetes and central nervous system diseases, by measuring cell viability following viral infection (using MTT) and appreciating the reduction of cytopathic effect (CPE). Hence, the 50% cytotoxic concentration (CC50), 50% inhibitory concentration (IC50) and selectivity index (SI) were determined. The essential oil turned out to be non-toxic against the tested cell line (CC50 = 1772.41 ± 0.95) μg/mL, have a relevant anti-Coxsckievirus B4 activity (IC50 = 2.24 ± 0.99) μg/mL and a high SI (789.66). Results presented here suggest that O. regalis EO is a potentially promising new source as active antiviral agent

Harnessing the hERG1/b1 integrin complex via a novel bispecific single-chain antibody: An effective strategy against solid cancers

mAbs, either mono- or bispecific (bsAb), represent one of the most successful approaches to treat many types of malignancies. However, there are certain limitations to the use of full length mAbs for clinical applications, which can be overcome by engineered antibody fragments. The aim of this study was to develop a small bsAb, in the format of a single-chain diabody (scDb), to efficiently target two proteins, the hERG1 potassium channel and the b1 subunit of integrin receptors, which specifically form a macromolecular complex in cancer cells. We provide evidence that the scDb we produced binds to the hERG1/b1 complex in cancer cells and tissues, but does not bind to the hERG1 channel in nonpathologic tissues, in particular the heart. The scDb-hERG1-b1 (i) downregulates the formation of the hERG1/b1 complex, (ii) inhibits Akt phosphorylation and HIF-1a expression, and (iii) decreases cell survival, proliferation, and migration in vitro. These effects only occur in cancer cells (either colon, pancreatic, or breast), but not in normal cells. In vivo, the scDb-hERG1-b1 shows a good pharmacokinetic profile, with a half-life of 13.5 hours and no general, cardiac, or renal toxicity when injected intravenously up to the dose of 8 mg/kg. The scDb-hERG1-b1 accumulates into subcutaneous xenografted tumors, arising from either colon or pancreatic human cancer cells, and induces a reduction of tumor growth and vascularization. Overall, the scDb-hERG1-b1 represents an innovative single-chain bispecific antibody for therapeutic applications in solid cancers that overexpress the hERG1/b1 integrin signaling complex