Sensitivity of PM10 oxidative potential to aerosol chemical composition at a Mediterranean urban site: ascorbic acid versus dithiothreitol measurements.

The oxidative potential (OP) of PM10 daily samples collected at a traffic site in southeastern Spain during summer and winter was assessed by two acellular assays: the ascorbic acid (AA) and dithiothreitol (DTT) methods. Although PM10 levels were similar during both periods, OP values (expressed in nmol min-1 m-3) showed a defined seasonal trend. The AA activity was higher in summer than in winter, whereas the DTT reactivity exhibited an opposite seasonal pattern. Both assays were sensitive to different PM10 components, as shown by the results of the linear correlation analysis. Moreover, the relationship between OP values and PM10 chemical species was not the same during summer and winter, indicating that particle toxicity is associated with different sources during the warm and cold seasons. When OP values were expressed on a mass basis (nmol min-1 µg-1), lower correlation coefficients with PM10 chemical species were generally obtained compared to volume-normalized activities. These outcomes suggest that only some specific components have a significant intrinsic oxidative potential. Supplementary Information: The online version contains supplementary material available at 10.1007/s11869-023-01332-1.

[Suspected allergy to COVID-19 vaccines: A retrospective study of 320 patients]. / Suspicion d'allergie aux vaccins anti COVID-19 : étude rétrospective sur 320 patients.

Introduction: The health context with COVID-19 pandemic has led to fast development of many vaccines against the SarS-Cov-2 virus. Four of them are currently available in France and contain polyethylene glycol (PEG) or polysorbate 80 as excipients, already described as causing anaphylaxis. French recommendations have been suggested by allergology authorities and proposed a course of action in the event of a suspected allergy to these vaccines. Thus, allergies to excipients were the only contraindication to COVID-19 vaccination. Our main objective was to determine the impact of these allergology vaccine recommendations on the management of these patients. Our secondary objective was to determine prevalence of true allergies to these vaccines. Materials and methods: We conducted a unicentric descriptive retrospective study with all patients over 18 years of age referred for an allergological opinion before or after an injection of one of the anti-COVID-19 vaccines. Nineteen patients were classified into different interest groups, based on french recommendations. Results: The vast majority of patients did not require a pre-vaccination allergological assessment. Indeed, only 25 patients received skin tests prior to vaccination. The rest of patients were able to be vaccinated without allergological assessment. Patients not vaccinated due to allergy to excipients represent less than 1% of the population (n = 3/320). Conclusion: French recommendations made it possible to vaccinate the vast majority of patients included in our study. Allergy to PEG, polysorbate or their derivatives, the only contraindication to anti-COVID vaccination, according to the recommendations of February 2021, remains rare. Today, several authors propose tolerance inductions allowing the vaccination of patients allergic to PEGs or their derivatives with good tolerance.

Size segregated ionic species collected in a harbour area.

Water-soluble ions were analysed in size segregated aerosol samples collected in the port of Alicante (Southeastern Spain) during summer and winter using a multistage cascade impactor. Seasonal variations in the size distributions of the analysed components and the influence of bulk materials handling (loading/unloading and stockpiling) at the docks were investigated. The size distributions of SO42-, NH4+ and K+ were characterized by prominent peaks in the condensation and droplet modes, both in summer and winter, while those of Ca2+, Na+, Mg2+ and Cl- had a main peak centred at ∼4 µm. Although oxalate size distributions were similar during both seasons, the fraction of coarse-mode oxalate increased in summer most likely as a result of volatilization and repartition processes or reactions of oxalic acid with coarse alkaline particles. Nitrate size distributions were dominated by a coarse mode; however, during winter, modal peaks in the submicron size range were also observed due to favourable conditions for the formation of fine-mode NH4NO3. Harbour activities had a significant impact only on the concentrations of calcium, particularly in the coarse fraction, during both summer and winter.

Quantification of the impact of port activities on PM10 levels at the port-city boundary of a mediterranean city.

The main objective of this work was to quantify the impact of handling of bulk materials on PM10 levels measured at the port-city border of Alicante (Spain), located on the western Mediterranean coast. To achieve that goal, 355 PM10 samples were collected at the perimeter of the harbor of Alicante from March 2017 to February 2018. A 181 sample subgroup was chemically characterized in order to perform a source apportionment study with the EPA PMF 5.0 model. Eight factors were identified, two of them directly related to the handling of bulk materials (Limestone + gypsum and Clinker), accounting jointly for 35% of the average PM10 concentration. A Road traffic factor was the second highest contributor to PM10 levels (17%) while the Shipping emissions factor accounted for only 6% of the average PM10 mass. Other factors such as Biomass burning+ secondary nitrate and Aged sea salt represented a joint contribution of 25% of the PM10 mass. Results indicate that emission abatement strategies should primarily focus on the reduction of fugitive emissions caused by the handling of bulk materials at the docks. Moreover, scenarios including reductions of more than 50% in bulk handling sources and 10% in other anthropogenic sources would help to reduce anthropogenic exceedances of the daily PM10 limit (50 µg·m-3) and to approach to WHO daily PM10 standard (20 µg m-3).

Physiopathologie de la dermatite atopique et des autres maladies atopiques : une approche globale est-elle possible ?: Pathophysiology of atopic dermatitis and other atopic diseases: is a global approach possible?

Atopy is defined by the propensity to develop an exaggerated type-2 inflammatory response to environmental molecules. Clinically, atopy is diagnosed when atopic disease occurs: atopic dermatitis, food allergy, atopic asthma and allergic rhinitis and conjunctivitis. Whereas the classical "atopic march" is increasingly challenged through epidemiological studies, type-2 cellular inflammation is a characteristic shared by the atopic diseases. This inflammation can be innate (non-specific: eosinophils, mast cells, dendritic cells, innate lymphoid cells [ILC]), or adaptive (antigen-specific, involving T cells). Interleukins (IL-)4, 5 and 13 are major actors of type-2 inflammation and are mainly produced by ILC and T cells. The efficacy of treatments targeting these type-2 cytokines highlight the importance of type-2 inflammation in atopic diseases. However, several patients do not respond to type-2 targeting treatments, highlighting the presence of other actors in pathophysiology of atopic diseases: alteration of epithelial barrier, IgE-mediated allergic responses, type-17 inflammation. Thus, the term "endotype" can illustrate this diversity in pathophysiology. Finally, a global approach of atopic diseases, as type-2 inflammatory diseases, is fundamental, but not sufficient. An approach by endotype is advisable, in a personalized medicine perspective. © 2020 Elsevier Masson SAS. All rights reserved.

PET ligands [18F]LSN3316612 and [11C]LSN3316612 quantify O-linked-ß-N-acetyl-glucosamine hydrolase in the brain.

We aimed to develop effective radioligands for quantifying brain O-linked-ß-N-acetyl-glucosamine (O-GlcNAc) hydrolase (OGA) using positron emission tomography in living subjects as tools for evaluating drug target engagement. Posttranslational modifications of tau, a biomarker of Alzheimer's disease, by O-GlcNAc through the enzyme pair OGA and O-GlcNAc transferase (OGT) are inversely related to the amounts of its insoluble hyperphosphorylated form. Increase in tau O-GlcNAcylation by OGA inhibition is believed to reduce tau aggregation. LSN3316612, a highly selective and potent OGA ligand [half-maximal inhibitory concentration (IC50) = 1.9 nM], emerged as a lead ligand after in silico analysis and in vitro evaluations. [3H]LSN3316612 imaged and quantified OGA in postmortem brains of rat, monkey, and human. The presence of fluorine and carbonyl functionality in LSN3316612 enabled labeling with positron-emitting fluorine-18 or carbon-11. Both [18F]LSN3316612 and [11C]LSN3316612 bound reversibly to OGA in vivo, and such binding was blocked by pharmacological doses of thiamet G, an OGA inhibitor of different chemotype, in monkeys. [18F]LSN3316612 entered healthy human brain avidly (~4 SUV) without radiodefluorination or adverse effect from other radiometabolites, as evidenced by stable brain total volume of distribution (VT) values by 110 min of scanning. Overall, [18F]LSN3316612 is preferred over [11C]LSN3316612 for future human studies, whereas either may be an effective positron emission tomography radioligand for quantifying brain OGA in rodent and monkey.

Therapeutic management of adults with atopic dermatitis: comparison with psoriasis and chronic urticaria.

BACKGROUND: The therapeutic options in atopic dermatitis rely on consensus-based guidelines, also established for psoriasis and chronic urticaria. However, the therapeutic approach in atopic dermatitis, especially in the moderate-to-severe forms of the disease, seems less aggressive than in psoriasis and in chronic urticaria with a less frequent use of systemic agents. OBJECTIVES: To compare in real-life conditions the therapeutic management of adults with atopic dermatitis with those with psoriasis and chronic urticaria. METHODS: A transversal analysis was performed in May 2017, using retrospective data from a monocentric database. Data on epidemiology, severity, therapeutic educational intervention and systemic treatments were analysed from 401 patients with atopic dermatitis, compared with data from 230 patients with chronic urticaria and 535 patients with psoriasis. RESULTS: A high proportion (73%) of atopic dermatitis patients presented with a moderate-to-severe form of the disease compared to only 39% of chronic urticaria and 17% of psoriasis patients. Most of atopic dermatitis patients (78%) had completed a therapeutic educational programme, while the adherence was lower in chronic urticaria (35%) and in psoriasis (3%) patients. A systemic treatment, including biologicals, was recorded in 8% of atopic dermatitis patients, while it concerned 26% and 47% of chronic urticaria and psoriasis patients, respectively. CONCLUSIONS: We confirmed that atopic dermatitis treatment mostly relies on topical treatments. Only a minority of moderate-to-severe atopic dermatitis patients who are eligible for a systemic treatment receive such therapy. This may suggest promoting a more frequent use of systemic agents in moderate-to-severe atopic dermatitis.

Insights into the origin and evolution of carbonaceous aerosols in a mediterranean urban environment.

Organic carbon (OC) and elemental carbon (EC) concentrations were measured in PM1 and PM10 daily samples collected at an urban station in Elche (southeastern Spain) from February 2015 to February 2018. The effect of seasonal weather conditions, traffic, and specific pollution events (Saharan dust outbreaks and local pollution episodes) on the variability of carbonaceous aerosol levels was studied in this work. The joint contribution of carbonaceous species to PM1 and PM10 mass concentrations was, respectively, 48% and 26%. Both OC and EC concentrations were higher in winter than in summer because of the poor dispersion conditions and lower temperatures leading to the condensation of semivolatile species. Secondary organic carbon (SOC), estimated using the EC tracer method, also exhibited higher concentrations during winter, indicating that the prevailing meteorological conditions during the cold season are more favorable for the formation of secondary organic aerosols. Our results suggest different formation pathways of secondary organic components during summer and winter. At the sampling site, EC was primarily derived from traffic emissions, independently of the season and the type of event, with a modest contribution from biomass burning (<20%). The estimated contribution from this source to OC levels was similar. Local pollution episodes lead to a significant increase in the concentrations of carbonaceous species, in particular of SOC, influencing its temporal variation. On average, African dust outbreaks showed a moderate impact on the levels of carbonaceous aerosols; however, the effect was significantly stronger during winter Saharan events.

Automatic depletion with Spectra Optia allows a safe 16% reduction of red blood cell pack consumption in exchanged sickle cell anemia patients.

BACKGROUND: Chronic red blood cell exchanges (RBCXs) are frequently used to prevent complications in patients with sickle cell anemia, but the scarcity of matched red blood cell packs (RBCPs) is a serious concern. The main goal of this study was to compare the number of RBCPs used during RBCXs between the Spectra Optia (SO) device (with the automatic depletion step) and the former Cobe Spectra (CSP) device. STUDY DESIGN AND METHODS: The performances and safety of 300 SO sessions using the automatic depletion step (SO/DE) in 50 patients with sickle cell anemia under a chronic transfusion program over a 1-year period were prospectively analyzed. The numbers of RBCPs saved using this protocol compared to the SO device without depletion and to the CSP device were determined. RESULTS: The SO/DE protocol appeared to be safe, as only 5% and 17% of the sessions were characterized by a significant decrease in blood pressure and increase in heart rate (grade 2 adverse events), respectively. Postapheresis hematocrit and fraction of cells remaining reached expected values. The SO/DE protocol required 16% fewer RBCPs compared to SO without depletion, allowing a mean saving of 12 RBCPs per patient and per year and 13% fewer compared to CSP device. Interestingly, the saving was more important for patients with high total blood volume and/or high preapheresis hematocrit. CONCLUSION: The SO/DE protocol is an efficient, safe and cost-effective procedure for patients with sickle cell anemia under a chronic transfusion program.

[NSAID urticaria: Similar management to acute urticaria]. / Urticaire aux AINS : une prise en charge similaire à celle de l'urticaire aiguë.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common providers of immediate hypersensitivity reactions. Among these reactions, isolated acute urticaria is the most common clinical feature with a non-allergic origin. It is a pharmacological side effect resulting from the alteration of arachidonic acid metabolism induced by NSAIDs. Diagnosis of this acute urticaria is clinical, requiring no allergy testing. Currently, the recommended therapeutic management of NSAID urticaria is the avoidance of all NSAID with COX-1 inhibitor activity (even if when reintroduced, they are most often well tolerated) and the use of selective COX-2 inhibitors. This review focuses on urticaria reactions to NSAIDs, which are simple to manage.

Epidermolysis bullosa simplex generalized severe induces a T helper 17 response and is improved by apremilast treatment.

BACKGROUND: Epidermolysis bullosa simplex generalized severe (EBS-gen sev) is a genetic disorder caused by mutation in the KRT5 or KRT14 genes. Although it is usually considered a mechanical disease, recent data argue for additional inflammatory mechanisms. OBJECTIVES: To assess the inflammation in the skin of patients with EBS-gen sev. METHODS: A first immunohistochemical retrospective study was performed on frozen skin samples from 17 patients with EBS-gen sev. A second multicentre prospective study was conducted on 10 patients with severe EBS-gen sev. Blister fluid and epidermis were processed for immunochemical analysis and quantitative real-time polymerase chain reaction. Cytokine expression was analysed in blister fluid and compared with that in controls. RESULTS: Histological analysis showed a constant dermal perivascular CD4+ lymphocyte infiltrate in skin biopsies of both blister (n = 17) and rubbed skin (n = 5), an epidermal infiltration of neutrophils and eosinophils in 70% of cases, and increased immunostaining for CXCL9 and CXCL10 in blistering skin. High levels of T helper 17 cytokines were detected in lesional skin. Three adult patients with EBS-gen sev were treated with apremilast, with a dramatic improvement of skin blistering and good tolerance. CONCLUSIONS: Our study demonstrates the importance of inflammation in patients with EBS-gen sev and underlines the key role for T helper 17 cells in its pathogenesis. In addition, this study provides promising new therapeutic approaches for this disabling disorder.

Characterization of metals in PM1 and PM10 and health risk evaluation at an urban site in the western Mediterranean.

PM1 and PM10 samples collected in the urban center of Elche during two years were analyzed by Energy Dispersive X-Ray Fluorescence in order to determine the concentrations of the following metals: K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, Sr and Ba. The influence of traffic and Saharan dust intrusions on PM levels and metal content was studied in this work. The results indicate that the coarse fraction was affected more by variations in traffic intensity than the submicron fraction. The concentrations of Ca, commonly used as a tracer of road dust, showed the highest decreases during the weekends due to the reduction in traffic-induced resuspension. In contrast, Saharan events had a greater impact on the levels of other metals such as Ti and Fe, significantly affecting their seasonal variability. High concentrations of V and Ni compared with the values found at larger urban areas were observed. This could be attributed to a significant contribution from soils, Saharan dust and even ship emissions. Enrichment factors calculated using Ti as a reference element indicate that Zn and Cu are predominantly emitted by anthropogenic activities. In fact, Saharan dust intrusions had a minor influence on the average concentrations of these metals. Non-carcinogenic health hazards associated with exposure to airborne metals were lower than the safety threshold (hazard quotient < 1). Carcinogenic risks for Cr (VI) and Ni were between 10-6 and 10-4 and, therefore, within the range considered acceptable by the US EPA.

Topical ivermectin improves allergic skin inflammation.

BACKGROUND: Ivermectin (IVM) is widely used in both human and veterinary medicine to treat parasitic infections. Recent reports have suggested that IVM could also have anti-inflammatory properties. METHODS: Here, we investigated the activity of IVM in a murine model of atopic dermatitis (AD) induced by repeated exposure to the allergen Dermatophagoides farinae, and in standard cellular immunological assays. RESULTS: Our results show that topical IVM improved allergic skin inflammation by reducing the priming and activation of allergen-specific T cells, as well as the production of inflammatory cytokines. While IVM had no major impact on the functions of dendritic cells in vivo and in vitro, IVM impaired T-cell activation, proliferation, and cytokine production following polyclonal and antigen-specific stimulation. CONCLUSION: Altogether, our results show that IVM is endowed with topical anti-inflammatory properties that could have important applications for the treatment of T-cell-mediated skin inflammatory diseases.

Comparative histological analysis of drug-induced maculopapular exanthema and DRESS.

BACKGROUND: Cutaneous adverse drug reactions frequently present as a benign maculopapular exanthema (MPE) with a rapid healing. Sometimes systemic signs are present, which could represent a more severe or systemic MPE (sMPE) or even be the initial phase of a drug reaction with eosinophilia and systemic symptoms (DRESS). Histopathology associated with MPE, sMPE and DRESS has not been well characterized. OBJECTIVES: To study the cutaneous histopathological changes associated with MPE, sMPE and DRESS. METHODS: A retrospective clinicopathological analysis of 13 cases of MPE, 13 of sMPE and 45 of DRESS, collected in one centre from 2005 to 2013. RESULTS: The number of histopathological changes per section increased gradually from MPE to sMPE and DRESS. Prevalence of spongiosis, dermal lymphocytes, eosinophils and neutrophils did not differ between MPE, sMPE and DRESS. Keratinocyte damage, rare in MPE, was regularly found in sMPE and frequent in DRESS. The density of the inflammatory infiltrate increased progressively from MPE to sMPE and DRESS. Atypical lymphocytes were absent in MPE, present in sMPE and more frequent in DRESS. Deep dermal involvement and leukocytoclastic vasculitis were only observed in DRESS. LIMITATIONS: This was a retrospective study. CONCLUSIONS: Numerous histopathological changes per section in drug-induced exanthema should alert for a more severe form of cutaneous adverse drug reactions, i.e. DRESS.

Depletion of tropospheric ozone associated with mineral dust outbreaks.

From May to September 2012, ozone reductions associated with 15 Saharan dust outbreaks which occurred between May to September 2012 have been evaluated. The campaign was performed at a mountain station located near the eastern coast of the Iberian Peninsula. The study has two main goals: firstly, to analyze the decreasing gradient of ozone concentration during the course of the Saharan episodes. These gradients vary from 0.2 to 0.6 ppb h(-1) with an average value of 0.39 ppb h(-1). The negative correlation between ozone and coarse particles occurs almost simultaneously. Moreover, although the concentration of coarse particles remained high throughout the episode, the time series shows the saturation of the ozone loss. The highest ozone depletion has been obtained during the last hours of the day, from 18:00 to 23:00 UTC. Outbreaks registered during this campaign have been more intense in this time slot. The second objective is to establish from which coarse particle concentration a significant ozone depletion can be observed and to quantify this reduction. In this regard, it has been confirmed that when the hourly particle concentration recorded during the Saharan dust outbreaks is above the hourly particle median values (N > N-median), the ozone concentration reduction obtained is statistically significant. An average ozone reduction of 5.5 % during Saharan events has been recorded. In certain cases, this percentage can reach values of higher than 15 %.

[Fixed drug eruption to clarithromycin: The importance of challenge tests in diagnosis]. / Érythème pigmenté fixe à la clarithromycine : importance des tests de provocation pour le diagnostic.

BACKGROUND: Determining the substance responsible for recurrent fixed drug eruption (FDE) may be difficult in the case of patients on multiple medication. Allergy testing may prove invaluable in such situations, as we demonstrate herein with an original case. PATIENTS AND METHODS: A 49-year-old man presented a rash on the seventh day of treatment with esomeprazole, clarithromycin and amoxicillin prescribed for gastritis involving Helicobacter pylori. The condition regressed spontaneously within a few days, but left three areas of hyperpigmentation. The patient subsequently reported four further episodes consisting of stereotypical reactivation in the areas of the three initial lesions and occurring 24hours after use of clarithromycin (2 episodes) and amoxicillin (2 episodes). The patient resumed proton pump inhibitor therapy (esomeprazole) without incident. Based on history taking, an initial diagnosis was made of multiple fixed drug eruption involving amoxicillin and clarithromycin. The initial skin allergy investigations were negative (patch-tests for amoxicillin and clarithromycin on healthy skin on the patient's back and on the affected area). After discussion, we decided to reintroduce the suspected drugs in succession. Beginning with clarithromycin, 12h after a single dose of 250mg, we noted an erythematous reaction on the pigmented areas, together with a burning sensation. In an identical challenge test with amoxicillin (500mg), the latter drug was perfectly well tolerated, ruling out the diagnosis of FDE to amoxicillin and thus the diagnosis of multiple FDE suggested by the patient history. DISCUSSION: FDEs to macrolides are rare, and herein we report a new case. Our observation confirms the diagnostic value of challenge tests in FDE. These tests should only be performed in the event of non-severe FDE, in other words not in bullous or systemic reactions, and they often constitute the only diagnostic approach possible, since skin tests are rarely positive during investigation for FDE.