Search

Background: Hand eczema (HE) is a highly prevalent, recurrent, and multifactorial disease. It encompasses a group of eczematous diseases that affect the hands, etiologically classified into irritant contact dermatitis (ICD), allergic contact dermatitis (ACD) and atopic dermatitis (AD). Few epidemiological studies in Latin America have investigated the characteristics of patients with this condition and the origin of the disease., Objectives: To analyze the profile of patients diagnosed with HE submitted to patch tests aiming to determine its etiology., Methods: A retrospective descriptive study was carried out on epidemiological data and patch tests of patients with HE treated at a tertiary hospital in the city of São Paulo from January 2013 to December 2020., Results: A total of 173 patients were studied, whose final diagnosis was 61.8% of ICD, 23.1% of ACD and 5.2% of AD, with diagnostic overlap in 42.8% of the cases. The main positive and relevant patch tests were: Kathon CG (42%), nickel sulfate (33%), and thiuram mix (18%)., Study Limitations: The number of treated cases and socioeconomic profile was limited to a vulnerable population group., Conclusion: HE is a diagnosis in which overlapping etiologies are frequent, with the main sensitizers identified in ACD being Kathon CG, nickel sulfate and thiuram mix., (Copyright © 2023. Published by Elsevier España, S.L.U.)

Seckel syndrome (SS) is a rare spectrum of congenital severe microcephaly and dwarfism. One SS-causative gene is Ataxia Telangiectasia and Rad3-Related Protein (ATR), and ATR (c.2101 A>G) mutation causes skipping of exon 9, resulting in a hypomorphic ATR defect. This mutation is considered the cause of an impaired response to DNA replication stress, the main function of ATR, contributing to the pathogenesis of microcephaly. However, the precise behavior and impact of this splicing defect in human neural progenitor cells (NPCs) is unclear. To address this, we established induced pluripotent stem cells (iPSCs) from fibroblasts carrying the ATR mutation and an isogenic ATR-corrected counterpart iPSC clone. SS-patient-derived iPSCs (SS-iPSCs) exhibited cell type-specific splicing; exon 9 was dominantly skipped in fibroblasts and iPSC-derived NPCs, but it was included in undifferentiated iPSCs and definitive endodermal cells. SS-iPSC-derived NPCs (SS-NPCs) showed distinct expression profiles from ATR non-mutated NPCs with negative enrichment of neuronal genesis-related gene sets. In SS-NPCs, abnormal mitotic spindles occurred more frequently than in gene-corrected counterparts, and the alignment of NPCs in the surface of the neurospheres was perturbed. Finally, we tested several splicing-modifying compounds and found that TG003, a CLK1 inhibitor, could pharmacologically rescue the exon 9 skipping in SS-NPCs. Treatment with TG003 restored the ATR kinase activity in SS-NPCs and decreased the frequency of abnormal mitotic events. In conclusion, our iPSC model revealed a novel effect of the ATR mutation in mitotic processes of NPCs and NPC-specific missplicing, accompanied by the recovery of neuronal defects using a splicing rectifier.

Melanoma Guidelines of the Brazilian Dermatology Society recommend histologic review by pathologists trained in melanocytic lesions whenever possible. Out of 145 melanoma cases identified at a private clinic in São Paulo/Brazil, 31 that had been submited to histologic review were studied to evaluate whether revision had led to change in therapeutic approach.. Differences in original/reviewed reports were found in 58.1% (n=18) of the reports, leading to changes in therapeutic approach in 41.9% (n=13). Change in diagnosis was observed in 6 out of 31 (19,3%) cases. These findings suggest that second opinion by pathologists trained in melanocytic lesions is likely to show significant differences from the original report.

Keys are a significant source of exposure to metal allergens and can be a relevant problem for nickel-allergic individuals. This study aimed to perform nickel and cobalt spot testing among the 5 most common Brazilian brands of keys. Among the tested keys, 100% showed positive result to nickel spot test, 83,3% presented strong positive reaction. 50% exhibited cobalt release as well. Nickel release from keys is very common in our country and may cause a negative impact on sensitized individual's quality of life. Study's results highlight the importance of establishing directives to regulate nickel release in Brazil.

Obtaining highly purified differentiated cells via directed differentiation from human pluripotent stem cells (hPSCs) is an essential step for their clinical application. Among the various conditions that should be optimized, the precise role and contribution of the extracellular matrix (ECM) during differentiation are relatively unclear. Here, using a short fragment of laminin 411 (LM411-E8), an ECM predominantly expressed in the vascular endothelial basement membrane, we demonstrate that the directed switching of defined ECMs robustly yields highly-purified (>95%) endothelial progenitor cells (PSC-EPCs) without cell sorting from hPSCs in an integrin-laminin axis-dependent manner. Single-cell RNA-seq analysis revealed that LM411-E8 resolved intercellular transcriptional heterogeneity and escorted the progenitor cells to the appropriate differentiation pathway. The PSC-EPCs gave rise to functional endothelial cells both in vivo and in vitro. We therefore propose that sequential switching of defined matrices is an important concept for guiding cells towards desired fate.

Fanconi anemia (FA) is a disorder of genomic instability characterized by progressive bone marrow failure (BMF), developmental abnormalities, and an increased susceptibility to cancer. Although various consequences in hematopoietic stem/progenitor cells have been attributed to FA-BMF, the quest to identify the initial pathological event is still ongoing. To address this issue, we established induced pluripotent stem cells (iPSCs) from fibroblasts of six patients with FA and FANCA mutations. An improved reprogramming method yielded iPSC-like colonies from all patients, and iPSC clones were propagated from two patients. Quantitative evaluation of the differentiation ability demonstrated that the differentiation propensity toward the hematopoietic and endothelial lineages is already defective in early hemoangiogenic progenitors. The expression levels of critical transcription factors were significantly downregulated in these progenitors. These data indicate that the hematopoietic consequences in FA patients originate from the early hematopoietic stage and highlight the potential usefulness of iPSC technology for elucidating the pathogenesis of FA-BMF., (©AlphaMed Press.)

A retrospective study was carried out between 2006-2011. Six hundred and eighteen patients with suspected allergic contact dermatitis underwent the standard patch test series recommended by the Brazilian Contact Dermatitis Research Group. The aim of our study was to evaluate the variation of positive patch-test results from standard series year by year. The most frequently positive allergens were: nickel sulfate, thimerosal and potassium bichromate. Decrease of positive patch-test results over the years was statistically significant for: lanolin (p=0.01), neomycin (p=0.01) and anthraquinone (p=0.04). A follow-up study should be useful in determining which allergens could be excluded from standard series, as they may represent low sensitization risk.