Role of ROS and HMGB1 in Contact Allergen–Induced IL-18 Production in Human Keratinocytes

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Lertal®, a multicomponent nutraceutical, could reduce the use of antihistamines in children with allergic rhinoconjunctivitis

Antihistamines are the cornerstone treatment of allergic rhinitis (AR). To quantify the antihistaminic consume is particularly relevant in clinical practice, since a remarkable use is usually associated with severe symptoms. The aim of the study was to measure the use of antihistamines in two groups of children suffering from AR. The first group took a course of a nutraceutical (Lertal®) before the observation (active group, AG); a second one was considered as control (control group, CG). Both groups took antihistamines on demand. The children were visited at baseline and after 1 year. The number of days of antihistaminic use was the primary outcome. Children in AG had a significant reduced number of antihistamines use in comparison with CG (p=0.008). In conclusion, the current study showed that a course with a multicomponent nutraceutical could reduce the use of symptomatic antihistamines in children with allergic rhinoconjunctivitis

Prognostic imaging biomarkers for diabetic kidney disease (iBEAt):study protocol

Background: Diabetic kidney disease (DKD) remains one of the leading causes of premature death in diabetes. DKD is classified on albuminuria and reduced kidney function (estimated glomerular filtration rate (eGFR)) but these have modest value for predicting future renal status. There is an unmet need for biomarkers that can be used in clinical settings which also improve prediction of renal decline on top of routinely available data, particularly in the early stages. The iBEAt study of the BEAt-DKD project aims to determine whether renal imaging biomarkers (magnetic resonance imaging (MRI) and ultrasound (US)) provide insight into the pathogenesis and heterogeneity of DKD (primary aim) and whether they have potential as prognostic biomarkers in DKD (secondary aim). Methods: iBEAt is a prospective multi-centre observational cohort study recruiting 500 patients with type 2 diabetes (T2D) and eGFR ≥30 ml/min/1.73m2. At baseline, blood and urine will be collected, clinical examinations will be performed, and medical history will be obtained. These assessments will be repeated annually for 3 years. At baseline each participant will also undergo quantitative renal MRI and US with central processing of MRI images. Biological samples will be stored in a central laboratory for biomarker and validation studies, and data in a central data depository. Data analysis will explore the potential associations between imaging biomarkers and renal function, and whether the imaging biomarkers improve the prediction of DKD progression. Ancillary substudies will: (1) validate imaging biomarkers against renal histopathology; (2) validate MRI based renal blood flow measurements against H2O15 positron-emission tomography (PET); (3) validate methods for (semi-)automated processing of renal MRI; (4) examine longitudinal changes in imaging biomarkers; (5) examine whether glycocalyx and microvascular measures are associated with imaging biomarkers and eGFR decline; (6) explore whether the findings in T2D can be extrapolated to type 1 diabetes. Discussion: iBEAt is the largest DKD imaging study to date and will provide valuable insights into the progression and heterogeneity of DKD. The results may contribute to a more personalised approach to DKD management in patients with T2D. Trial registration: Clinicaltrials.gov (NCT03716401)

Eight Weddings and Six Funerals: An fMRI Study on Autobiographical Memories

“Autobiographical memory” (AM) refers to remote memories from one's own life. Previous neuroimaging studies have highlighted that voluntary retrieval processes from AM involve different forms of memory and cognitive functions. Thus, a complex and widespread brain functional network has been found to support AM. The present functional magnetic resonance imaging (fMRI) study used a multivariate approach to determine whether neural activity within the AM circuit would recognize memories of real autobiographical events, and to evaluate individual differences in the recruitment of this network. Fourteen right-handed females took part in the study. During scanning, subjects were presented with sentences representing a detail of a highly emotional real event (positive or negative) and were asked to indicate whether the sentence described something that had or had not really happened to them. Group analysis showed a set of cortical areas able to discriminate the truthfulness of the recalled events: medial prefrontal cortex, posterior cingulate/retrosplenial cortex, precuneus, bilateral angular, superior frontal gyri, and early visual cortical areas. Single-subject results showed that the decoding occurred at different time points. No differences were found between recalling a positive or a negative event. Our results show that the entire AM network is engaged in monitoring the veracity of AMs. This process is not affected by the emotional valence of the experience but rather by individual differences in cognitive strategies used to retrieve AMs

Detection and attribution of an anomaly in terrestrial photosynthesis in Europe during the COVID-19 lockdown

Carbon dioxide (CO2) uptake by plant photosynthesis, referred to as gross primary production (GPP) at the ecosystem level, is sensitive to environmental factors, including pollutant exposure, pollutant uptake, and changes in the scattering of solar shortwave irradiance (SWin) - the energy source for photosynthesis. The 2020 spring lockdown due to COVID-19 resulted in improved air quality and atmospheric transparency, providing a unique opportunity to assess the impact of air pollutants on terrestrial ecosystem functioning. However, detecting these effects can be challenging as GPP is influenced by other meteorological drivers and management practices. Based on data collected from 44 European ecosystem-scale CO2 flux monitoring stations, we observed significant changes in spring GPP at 34 sites during 2020 compared to 2015-2019. Among these, 14 sites showed an increase in GPP associated with higher SWin, 10 sites had lower GPP linked to atmospheric and soil dryness, and seven sites were subjected to management practices. The remaining three sites exhibited varying dynamics, with one experiencing colder and rainier weather resulting in lower GPP, and two showing higher GPP associated with earlier spring melts. Analysis using the regional atmospheric chemical transport model (LOTOS-EUROS) indicated that the ozone (O-3) concentration remained relatively unchanged at the research sites, making it unlikely that O-3 exposure was the dominant factor driving the primary production anomaly. In contrast, SWin increased by 9.4 % at 36 sites, suggesting enhanced GPP possibly due to reduced aerosol optical depth and cloudiness. Our findings indicate that air pollution and cloudiness may weaken the terrestrial carbon sink by up to 16 %. Accurate and continuous ground-based observations are crucial for detecting and attributing subtle changes in terrestrial ecosystem functioning in response to environmental and anthropogenic drivers

Substantial hysteresis in emergent temperature sensitivity of global wetland CH4 emissions

Wetland methane (CH4) emissions (FCH4) are important in global carbon budgets and climate change assessments. Currently, FCH4 projections rely on prescribed static temperature sensitivity that varies among biogeochemical models. Meta-analyses have proposed a consistent FCH4 temperature dependence across spatial scales for use in models; however, site-level studies demonstrate that FCH4 are often controlled by factors beyond temperature. Here, we evaluate the relationship between FCH4 and temperature using observations from the FLUXNET-CH4 database. Measurements collected across the globe show substantial seasonal hysteresis between FCH4 and temperature, suggesting larger FCH4 sensitivity to temperature later in the frost-free season (about 77% of site-years). Results derived from a machine-learning model and several regression models highlight the importance of representing the large spatial and temporal variability within site-years and ecosystem types. Mechanistic advancements in biogeochemical model parameterization and detailed measurements in factors modulating CH4 production are thus needed to improve global CH4 budget assessments. Wetland methane emissions contribute to global warming, and are oversimplified in climate models. Here the authors use eddy covariance measurements from 48 global sites to demonstrate seasonal hysteresis in methane-temperature relationships and suggest the importance of microbial processes.Peer reviewe

Safety Evaluation of Cosmetic Ingredients: In Vitro Opportunities for the Identification of Contact Allergens

Irritant and allergic contact dermatitis are undesired side effects in the development of drugs and cosmetics as well as after contact with environmental or industrial chemicals. Over the last decades, a great deal of progress has been made in the development of alternative In vitro test to assess these issues. Driven by the 7th Amendment to the European Cosmetic Directive, the EU policy on chemicals (the registration, evaluation, authorization and restriction of chemicals (REACH) system), the update of the European legislation on the protection of animals used in research, and emerging visions and strategies for predicting toxicity, in vitro methods are likely to play a major role in the near future. On 12 December 2013, the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM, part of the European Commission Joint Research Centre) published its Recommendation on the Direct Peptide Reactivity Assay (DPRA) for skin sensitization, capable of distinguishing sensitizers from non-sensitizers. Other assays (i.e., KeratinoSens™ assay) will follow shortly. While a number of methods are at various stages of development and use, currently it is not possible to rank chemicals for their sensitizing potency, an issue that is important for a full safety assessment. It is expected that a predictive method to totally replace animal testing will be in the form of a test battery comprising molecular, cell-based, and/or computational methods, the so-called “Integrated Approaches to Testing and Assessment”. This review aims to discuss the state-of-the-art in the field of in vitro assessment of contact sensitizers

Clinical Translation of Microbiome Research in Alopecia Areata: A New Perspective?

The continuous research advances in the microbiome field is changing clinicians’ points of view about the involvement of the microbiome in human health and disease, including autoimmune diseases such as alopecia areata (AA). Both gut and cutaneous dysbiosis have been considered to play roles in alopecia areata. A new approach is currently possible owing also to the use of omic techniques for studying the role of the microbiome in the disease by the deep understanding of microorganisms involved in the dysbiosis as well as of the pathways involved. These findings suggest the possibility to adopt a topical approach using either cosmetics or medical devices, to modulate or control, for example, the growth of overexpressed species using specific bacteriocins or postbiotics or with pH control. This will favour at the same time the growth of beneficial bacteria which, in turn, can impact positively both the structure of the scalp ecosystem on the host’s response to internal and external offenders. This approach, together with a “systemic” one, via oral supplementation, diet, or faecal transplantation, makes a reliable translation of microbiome research in clinical practice and should be taken into consideration every time alopecia areata is considered by a clinician

Clinical Translation of Microbiome Research in Alopecia Areata: A New Perspective?

The continuous research advances in the microbiome field is changing clinicians’ points of view about the involvement of the microbiome in human health and disease, including autoimmune diseases such as alopecia areata (AA). Both gut and cutaneous dysbiosis have been considered to play roles in alopecia areata. A new approach is currently possible owing also to the use of omic techniques for studying the role of the microbiome in the disease by the deep understanding of microorganisms involved in the dysbiosis as well as of the pathways involved. These findings suggest the possibility to adopt a topical approach using either cosmetics or medical devices, to modulate or control, for example, the growth of overexpressed species using specific bacteriocins or postbiotics or with pH control. This will favour at the same time the growth of beneficial bacteria which, in turn, can impact positively both the structure of the scalp ecosystem on the host’s response to internal and external offenders. This approach, together with a “systemic” one, via oral supplementation, diet, or faecal transplantation, makes a reliable translation of microbiome research in clinical practice and should be taken into consideration every time alopecia areata is considered by a clinician