Label-free electrochemical immunosensor as a reliable point-of-care device for the detection of Interleukin-6 in serum samples from patients with psoriasis

interleukin-6 (IL-6) plays a crucial role in autoimmunity and chronic inflammation. this study aims to develop a low-cost, simple-to-manufacture, and user-friendly label-free electrochemical point-of-care device for the rapid detection of IL-6 in patients with psoriasis. precisely, a sandwich-based format immunosensor was developed using two primary antibodies (mAb-IL6 clone-5 and clone-7) and screen-printed electrodes modified with an inexpensive recycling electrochemical enhancing material, called biochar. mAb-IL6 clone-5 was used as a covalently immobilized capture bioreceptor on modified electrodes, and mAb-IL6 clone-7 was used to recognize the immunocomplex (Anti-IL6 clone-5 and IL-6) and form the sandwich. cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to conduct electrochemical characterization of the layer-by-layer assembly of the immunosensor, while square wave voltammetry (SWV) was used to perform the sensing. the developed immunosensor demonstrated robust analytical performance in buffer solution, with a wide linear range (LR) by varying from 2 to 250 pg/mL, a good limit of detection (LOD) of 0.78 pg/mL and reproducibility (RSD<7%). In addition, a spectrophotometric ELISA kit was employed to validate the results obtained with the label-free device by analyzing twenty-five serum samples from control and patients affected by psoriasis. a strong correlation in terms of pg/mL concentration of IL-6 was found comparing the two methods, with the advantage for our label-free biosensor of an ease use and a quicker detection time. based on IL-6 levels, the proposed immunosensor is a dependable, non-invasive screening device capable of predicting disease onset, progression, and treatment efficacy

Patient survival after renal transplantation: IV. Impact of post-transplant diabetes

Patient survival after renal transplantation: IV. Impact of post-transplant diabetes.BackgroundThe development of de novo diabetes mellitus is a serious complication of kidney transplantation. This study examined the cardiovascular risk profile of patients with post-transplant diabetes (PTDM) and assessed the impact of PTDM on patient survival.MethodsThis analysis included 1811 adult, renal allograft recipients, transplanted in a single institution between 1983 and 1998. Patient survival was analyzed by univariable and multivariable Cox regression considering PTDM as a time dependent variable.ResultsAfter a follow-up period of 8.3 ± 4.5 years, 293 patients (20%) developed PTDM, 14% lost their graft, and 20% died. Compared to patients without DM (NoDM, N = 1186) patients with PTDM were significantly older (40 ± 14 vs. 48 ± 12 years, P < 0.001), heavier (76 ± 23 vs. 86 ± 25 kg, P < 0.001), and included more African Americans (18 vs. 28%, P = 0.001). In addition, the incidence of PTDM was significantly higher in patients who were transplanted after 1995 than prior to that year. In contrast, there were no significant differences between PTDM and patients who had DM before the transplant (DM; N = 332). Compared to NoDM, patients with PTDM had significantly higher total serum cholesterol and triglycerides (TG), higher systolic blood pressure and higher pulse pressure throughout the post-transplant period. Of interest, all of these abnormalities preceded the development of PTDM. Hypertriglyceridemia was particularly pronounced in PTDM and elevated TG levels correlated with the subsequent development of PTDM, independent of other risk factors (P = 0.001 by multivariate Cox). Compared to NoDM (16% mortality) a significantly higher percent of DM (31%, P < 0.001) and PTDM (22%, P = 0.005) patients died. By Cox regression, PTDM correlated with reduced patient survival (hazard ratio = 1.80, CI 1.35 to 2.41, P = 0.001), and that relationship was independent of other correlates of reduced survival that included: increasing age; transplant year; reduced serum albumin; and male sex.Conclusions: PTDM is associated with an unfavorable cardiovascular risk profile that precedes the development of hyperglycemia. PTDM is an independent predictor of reduced survival in renal allograft recipients

Fluvial carbon export from a lowland Amazonian rainforest in relation to atmospheric fluxes

We constructed a whole carbon budget for a catchment in the Western Amazon Basin, combining drainage water analyses with eddy covariance measured terrestrial CO2 fluxes. As fluvial C export can represent permanent C export it must be included in assessments of whole site C balance, but is rarely done. The footprint area of the flux tower is drained by two small streams (~5-7 km2) from which we measured the dissolved inorganic carbon (DIC), dissolved organic carbon (DOC), particulate organic carbon (POC) export and CO2 efflux. The EC measurements showed the site C balance to be +0.7 ± 9.7 Mg C ha-1 yr-1 (a source to the atmosphere) and fluvial export was 0.3 ± 0.04 Mg C ha-1 yr-1. Of the total fluvial loss 34% was DIC, 37% DOC and 29% POC. The wet season was most important for fluvial C export. There was a large uncertainty associated with the EC results and with previous biomass plot studies (-0.5 ± 4.1 Mg C ha-1 yr-1), hence it cannot be concluded with certainty whether the site is C sink or source. The fluvial export corresponds to only 3-7 % of the uncertainty related to the site C balance, thus other factors need to be considered to reduce the uncertainty and refine the estimated C balance. However, stream C export is significant, especially for almost neutral sites where fluvial loss may determine the direction of the site C balance. The fate of C downstream then dictates the overall climate impact of fluvial export

Overview of the molecular determinants contributing to the expression of Psoriasis and Psoriatic Arthritis phenotypes

Psoriasis and psoriatic arthritis are multifactorial chronic disorders whose etiopathogenesis essentially derives from the alteration of several signalling pathways and the co-occurrence of genetic, epigenetic and non-genetic susceptibility factors that altogether affect the functional and structural property of the skin. Although shared and differential susceptibility genes and molecular pathways are known to contribute to the onset of pathological phenotypes, further research is needed to dissect the molecular causes of psoriatic disease and its progression towards Psoriatic Arthritis. This review will therefore be addressed to explore differences and similarities in the etiopathogenesis and progression of both disorders, with a particular focus on genes involved in the maintenance of the skin structure and integrity (keratins and collagens), modulation of patterns of recognition (through Toll-like receptors and dectin-1) and immuno-inflammatory response (by NLRP3-dependent inflammasome) to microbial pathogens. In addition, special emphasis will be given to the contribution of epigenetic elements (methylation pattern, non-coding RNAs, chromatin modifiers and 3D genome organization) to the etiopathogenesis and progression of psoriasis and psoriatic arthritis. The evidence discussed in this review highlights how the knowledge of patients' clinical and (epi)genomic make-up could be helpful for improving the available therapeutic strategies for psoriasis and psoriatic arthritis treatment

Trifarotene: a current review and perspectives in dermatology

Retinoids have numerous applications in inflammatory, dyskeratotic, and oncohematology diseases. Retinoids have now reached the fourth generation, progressively reducing toxicity whilst increasing their efficacy. Trifarotene is a new fourth-generation retinoid with a selective action on RAR-γ. In this review, we reported the trials—both concluded and in progress—including the use of trifarotene in dermatological diseases. Studies were identified by searching electronic databases (MEDLINE, EMBASE, PubMed, Cochrane, Trials.gov) from 2012 to today and reference lists of respective articles. Only articles published in English language were included. Randomized trials evaluating trifarotene tolerability, safety, and efficacy in congenital ichthyosis and acne have demonstrated great results and mild side effects, leading to the approval by the FDA of trifarotene for the treatment of lamellar ichthyosis in 2014, and of acne vulgaris in October 2019. No high-quality randomized clinical trials have evaluated the treatment of primary cutaneous lymphomas with trifarotene. Finally, we are hypothesizing future perspectives in the treatment of non-melanoma skin cancers, fungal infections, photoaging, and hand-foot skin reactions with trifarotene