Measurement of nickel, cobalt and chromium in toy make-up by atomic absorption spectroscopy.

Cosmetics should not contain more than 5 ppm of nickel, chromium or cobalt and, in order to minimize the risk of sensitization in very sensitive subjects, the target amount should be as low as 1 ppm. However, there are no published reports on the presence of these metals in toy make-up. This study analysed 52 toy make-ups using atomic absorption spectroscopy. More than 5 ppm of nickel was present in 14/52 (26.9%) samples. Chromium exceeded 5 ppm in 28/52 (53.8%) samples, with values over 1000 ppm in 3 eye shadows. Cobalt was present in amounts over 5 ppm in 5/52 (9.6%) samples. Powdery toy make-up (eye shadows) had the highest levels of metals, and "creamy" toy make-up (lip gloss and lipsticks) the lowest. Toy make-ups are potentially sensitizing items, especially for atopic children, who have a damaged skin barrier that may favour penetration of allergens

Results from an extended study on the reliability of a questionnaire for the diagnosis of sensitive skin: Confirmations and improvements

ObjectiveA recently proposed self-assessment questionnaire aimed at diagnosing sensitive skin provided promising results in a relatively small population. The main objectives were: (i) to assess the reliability of the aforementioned questionnaire in a larger population and verify the cut-off score previously found to predict skin sensitivity (defined as positivity to LAST, lactic acid stinging test) and (ii) to define a formula that yields the probability of a positive LAST result. MethodsAdult volunteers were included in this observational, cross-sectional, extended study. Both LAST-positive subjects, who were considered as having sensitive skin ('patients') and negative ones ('controls') completed the questionnaire, which concerned sensitivity to possible triggers of unpleasant skin sensations in real life. A cumulative score (questionnaire-based skin sensitivity score, 0-10) was calculated from the sum of all items. ResultsThree hundred and sixty-four subjects were enrolled, 214 patients and 150 controls. The mean questionnaire-based skin sensitivity score was significantly higher among patients than controls. Using two different methods, cut-off values of 4 and 5 were defined for the identification of LAST-positive subjects, with 76.6% and 72.8% accuracy, respectively. Scores below 4 or above 5 showed a high (80% or better) negative or positive predictive value, respectively. The coefficients found that in multivariate analysis for each questionnaire item, gender and age allowed us to calculate the probability of LAST positivity with higher precision taking into account the 'relative weight' of each factor. ConclusionWith small variations in the results, the self-assessment questionnaire confirmed its reliability for diagnosing sensitive skin in clinical practice

Doubtful Value of Patch Testing for Suspected Contact Allergy to Ophthalmic Products

Sir, Allergic contact dermatitis is the most common cause of peri-orbital eczema (1). It may be caused by allergens brought in contact with the eyelids by hand transfer (like toluene sulfonamide-formaldehyde resin in nail polishes), by airborne contact (like sesquiterpene lactones) or, most frequently, by direct application of cosmetics or topical ophthalmic medicaments. The percentage of sensitization due to cosmetics, such as moisturizing creams or eye-shadows, is estimated to range from 2.5% to 26% (2, 3). However, topical ophthalmic drugs, eye drops and contact lens solutions play a considerable role too. We studied 62 patients with eyelid dermatitis, closely related to the use of topical ocular products, with the aim of discerning the role of ophthalmic products in eyelid allergic contact dermatitis

primary cervicofacial nocardiosis due to nocardia asteroides in an adult immunocompetent patient

Sir, The Nocardia species are aerobic, lamentous grampositive bacteria, irregularly acid-fast staining that belong to the order Actinomycetales. Normally, Nocardia spp. are soil saprophytes, but N. asteroides may be found in the normal ora of the oral cavity and upper respiratory tract. Four species of Nocardia are pathogenic in man: N. asteroides, N. brasiliensis, N. caviae and N. madurae (1). N. asteroides is usually the agent of systemic pulmonary infections in immunocompromised hosts, while N. brasiliensis is the responsible agent in 74% of all cutaneous manifestations (1, 2). The skin is generally secondarily involved in disseminated systemic pulmonary diseases, due to haematogenous spread of N. asteroides, but it can also be primarily aVected. Primary cutaneous nocardiosis (PCN) accounts for only 5% of all nocardial infections and is caused mainly by N. brasiliensis (3, 4). PCN is characterized by numerFig. 1. In ammatory and ulcerative lesion of the nose. ous clinical manifestations: chronic mycetoma, super cial abscesses and cellulitis and lymphocutaneous increased ESR (93mm/h). Paraneoplastic serological variants. The last of these manifestations includes the markers, immunological investigations and HIV-1/2 more common sporotrichoid form (nodules along the serology were negative. Hemocultures were also lymphatic drainage) and the rarer cervicofacial variant. negative. We report an unusual case of primary cervicofacial Skull and chest X-rays were negative while ultrasononocardiosis caused by N. asteroides in an adult graphy revealed gross hypoecogenic non-homogeneous immunocompetent man. areas (colliquated lymph nodes) extending to the subfascial area. Sonography also showed numerous colliquated CASE REPORT lymph nodes in the right laterocervical region as well as a colliquative involvement of both the parotides and A 79-year-old man was admitted to our department because of fever and a necrotic ulcerative lesion of the submandibular lymph nodes. Computerized axial tomography of the head con rmed all the data and again dorsum of his nose. The borders were vegetant, in ltrated on palpation and a purulent exudate was easily showed abscesses of the left masseter muscle and the left submandibular salivary gland. obtained through compression. Numerous sparse tiny pustules and little pus-draining sinuses were peripherHistology of a skin biopsy taken from the borders of the ulcer only revealed a dense diVuse in ammatory ically sparse around the ulcerative lesion (Fig. 1). The in ammatory oedema involved the left cheek and the in ltrate of neutrophils and lymphocytes in the deep dermis, with abscess formation. No fungic elements were lower eyelid. A hardened swelling of the left mandibular angle and some hard, enlarged, latero-cervical lymph observed with PAS staining. Endovenous therapy with amoxicillin/clavulanic acid nodes were present. History revealed that the patient had had a bicycle 6.6 g/day, amikacin 1 g/day and teicoplanin 800mg/day was immediately started. A week later a slight improveaccident 15 days earlier, causing wounds on his forehead, nose and left cheek. The wounds had healed rapidly ment of the purulent and in ammatory aspects of the facial lesions was observed but the laterocervical tumewith common antiseptic medications. Blood sample examination revealed white blood factions had worsened and required surgical drainage. Cultures of purulent exudate from the nose ulcer, cells 13 109/l (60% neutrophils, 25% monocytes) an

Probing the influence of citrate-capped gold nanoparticles on an amyloidogenic protein

Nanoparticles (NPs) are known to exhibit distinct physical and chemical properties compared with the same materials in bulk form. NPs have been repeatedly reported to interact with proteins, and this interaction can be exploited to affect processes undergone by proteins, such as fibrillogenesis. Fibrillation is common to many proteins, and in living organisms, it causes tissue-specific or systemic amyloid diseases. The nature of NPs and their surface chemistry is crucial in assessing their affinity for proteins and their effects on them. Here we present the first detailed structural characterization and molecular mechanics model of the interaction between a fibrillogenic protein, \u3b22-microglobulin, and a NP, 5 nm hydrophilic citrate-capped gold nanoparticles. NMR measurements and simulations at multiple levels (enhanced sampling molecular dynamics, Brownian dynamics, and Poisson-Boltzmann electrostatics) explain the origin of the observed protein perturbations mostly localized at the amino-terminal region. Experiments show that the protein-NP interaction is weak in the physiological-like, conditions and do not induce protein fibrillation. Simulations reproduce these findings and reveal instead the role of the citrate in destabilizing the lower pH protonated form of \u3b22-microglobulin. The results offer possible strategies for controlling the desired effect of NPs on the conformational changes of the proteins, which have significant roles in the fibrillation process

Visits to Sexually Transmitted Infection Clinics in Italy from January 2016 to November 2021: A Multicenter, Retrospective Study

There is no evidence of seasonal variation in visits to clinics dedicated to sexually transmitted infections (STIs) in Italy, nor of changes after the advent of the COVID-19 pandemic. An observational, retrospective, multicentric study was conducted to record and analyze all the visits to the STI clinics of the Dermatology Units of the University Hospitals of Ferrara and Bologna and of the Infectious Disease Unit of Ferrara, Italy, between January 2016 and November 2021. Overall, 11.733 visits were registered over a 70-month study period (63.7% males, mean age 34.5 ± 12.8 yrs). The mean number of monthly visits significantly decreased from the advent of the pandemic (136) compared to before (177). In the pre-pandemic period, visits to STI clinics increased in the autumn/winter months when compared to spring/summer, while the trend was the opposite in the pandemic period. Thus, during the pandemic, both an overall significant reduction in visits to STI clinics and a reversal in their seasonality were observed. These trends affected males and females equally. The marked decrease, mostly found in the pandemic winter months, can be linked to the “lockdown”/self-isolation ordinances and social distancing measures during the colder months, coinciding with the spread of the COVID-19 infection, which limited the opportunities for meeting and socializing

Properties of Some Variants of Human β2-Microglobulin and Amyloidogenesis

Three variants of human beta(2)-microglobulin (beta(2)-m) were compared with wild-type protein. For two variants, namely the mutant R3Abeta(2)-m and the form devoid of the N-terminal tripeptide (DeltaN3beta(2)-m), a reduced unfolding free energy was measured compared with wild-type beta(2)-m, whereas an increased stability was observed for the mutant H31Ybeta(2)-m. The solution structure could be determined by (1)H NMR spectroscopy and restrained modeling only for R3Abeta(2)-m that showed the same conformation as the parent species, except for deviations at the interstrand loops. Analogous conclusions were reached for H31Ybeta(2)-m and DeltaN3beta(2)-m. Precipitation and unfolding were observed over time periods shorter than 4-6 weeks with all the variants and, sometimes, with wild-type protein. The rate of structured protein loss from solution as a result of precipitation and unfolding always showed pseudo-zeroth order kinetics. This and the failure to observe an unfolded species without precipitation suggest that a nucleated conformational conversion scheme should apply for beta(2)-m fibrillogenesis. The mechanism is consistent with the previous and present results on beta(2)-m amyloid transition, provided a nucleated oligomeric species be considered the stable intermediate of fibrillogenesis, the monomeric intermediate being the necessary transition step along the pathway from the native protein to the nucleated oligomer

Amyloid Formation by Globular Proteins: The Need to Narrow the Gap Between in Vitro and in Vivo Mechanisms

The globular to fibrillar transition of proteins represents a key pathogenic event in the development of amyloid diseases. Although systemic amyloidoses share the common characteristic of amyloid deposition in the extracellular matrix, they are clinically heterogeneous as the affected organs may vary. The observation that precursors of amyloid fibrils derived from circulating globular plasma proteins led to huge efforts in trying to elucidate the structural events determining the protein metamorphosis from their globular to fibrillar state. Whereas the process of metamorphosis has inspired poets and writers from Ovid to Kafka, protein metamorphism is a more recent concept. It is an ideal metaphor in biochemistry for studying the protein folding paradigm and investigating determinants of folding dynamics. Although we have learned how to transform both normal and pathogenic globular proteins into fibrillar polymers in vitro, the events occurring in vivo, are far more complex and yet to be explained. A major gap still exists between in vivo and in vitro models of fibrillogenesis as the biological complexity of the disease in living organisms cannot be reproduced at the same extent in the test tube. Reviewing the major scientific attempts to monitor the amyloidogenic metamorphosis of globular proteins in systems of increasing complexity, from cell culture to human tissues, may help to bridge the gap between the experimental models and the actual pathological events in patients

Awareness of obesity among patients with psoriasis

Dear Editor, Chronic plaque psoriasis is frequently associated with metabolic comorbidities, including obesity that have an important impact on the disease

A specific nanobody prevents amyloidogenesis of D76N \u3b22-microglobulin in vitro and modifies its tissue distribution in vivo

Systemic amyloidosis is caused by misfolding and aggregation of globular proteins in vivo for which effective treatments are urgently needed. Inhibition of protein self-aggregation represents an attractive therapeutic strategy. Studies on the amyloidogenic variant of \u3b22-microglobulin, D76N, causing hereditary systemic amyloidosis, have become particularly relevant since fibrils are formed in vitro in physiologically relevant conditions. Here we compare the potency of two previously described inhibitors of wild type \u3b22-microglobulin fibrillogenesis, doxycycline and single domain antibodies (nanobodies). The \u3b22-microglobulin -binding nanobody, Nb24, more potently inhibits D76N \u3b22-microglobulin fibrillogenesis than doxycycline with complete abrogation of fibril formation. In \u3b22-microglobulin knock out mice, the D76N \u3b22-microglobulin/ Nb24 pre-formed complex, is cleared from the circulation at the same rate as the uncomplexed protein; however, the analysis of tissue distribution reveals that the interaction with the antibody reduces the concentration of the variant protein in the heart but does not modify the tissue distribution of wild type \u3b22-microglobulin. These findings strongly support the potential therapeutic use of this antibody in the treatment of systemic amyloidosis