Epidemiological, Clinical, and Allergic Profile of Psoriatic Patients. Evaluation of the Spanish Registry of Contact Dermatitis and Cutaneous Allergy (REIDAC). / Perfil epidemiológico, clínico y alérgico en pacientes con psoriasis. Evaluación del Registro Español de Dermatitis de Contacto (REIDAC).

BACKGROUND: Psoriasis is a chronic inflammatory dermatosis whose clinical and topographic distribution requires differential diagnosis, or the possible association with allergic contact dermatitis (ACD), requiring patch testing (PT) as part of the diagnostic procedure. OBJECTIVES: To describe the epidemiological, clinical, and allergic profile of patients with a primary or secondary diagnosis of psoriasis undergoing PT and compare them with patients with a diagnosis of ACD at the end of the diagnostic process. METHODS: Cross-sectional study with data from REIDAC from 2018 through 2023 of selected patients with a diagnosis of psoriasis and/or ACD. RESULTS: A total of 11 502 patients were included, 513 of whom had been diagnosed with primary or secondary psoriasis, 3640 with ACD, and 108 with both diseases. Men were more predominant in the groups of patients with psoriasis, psoriasis+ACD, and lesions were more predominantly seen in the hands with little association with atopic factors vs the ACD group. The rate of positivity in PT to the 2022 Spanish battery of allergens was lower in the group with psoriasis only in 27% of the patients. The most common allergens found in the psoriasis group were also the most common ones found in the overall ACD population. CONCLUSIONS: Overall, 36.2% of psoriatic patients tested positive in PT to the 2022 Spanish battery of allergens, which proved that this association is not uncommon. Overall, psoriatic patients had a higher mean age, were more predominantly men, and showed more hand involvement.

Standard and Expanded Series Patch Testing Update by the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC). / Actualización de la batería estándar y batería ampliada de pruebas alérgicas de contacto por el Grupo Español de Investigación en Dermatitis de Contacto y Alergia Cutánea (GEIDAC).

After the meeting held by the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) back in October 2021, changes were suggested to the Spanish standard series patch testing. Hydroxyethyl methacrylate (2% pet.), textile dye mixt (6.6% pet.), linalool hydroperoxide (1% pet.), and limonene hydroperoxide (0.3% pet.) were, then, added to the series that agreed upon in 2016. Ethyldiamine and phenoxyethanol were excluded. Methyldibromoglutaronitrile, the mixture of sesquiterpene lactones, and hydroxyisohexyl 3-cyclohexene (Lyral) were alo added to the extended Spanish series of 2022.

Acquired vibratory angioedema with a severe impact on work performance.

Vibratory urticaria/angioedema is an inducible type of urticaria that may be elicited by vibratory stimuli from work tool and instruments. A 39-year-old male construction worker was diagnosed with acquired vibratory angioedema associated with chronic spontaneous urticaria involving a severe work performance impairment. Response to omalizumab was immediate and complete. We evaluated the Urticarial Activity Score; the response to the vibratory angioedema provocation vortex test; and evolution of analytical parameters (e.g. high-affinity IgE receptor expression on peripheral blood basophils, C-reactive protein, D-dimer and IgE levels). Vibratory angioedema may be misdiagnosed as delayed pressure urticaria if the appropriate specific provocation tests are not performed. According to our knowledge, this is the first time a pneumatic hammer is described as a trigger; the first case responding to omalizumab; and the second published case associated with spontaneous chronic urticaria.

Epidemiological, Clinical, and Allergy Profile of Patients With Atopic Dermatitis and Hand Eczema: Evaluation of the Spanish Contact Dermatitis Registry (REIDAC). / Perfil epidemiológico, clínico, y alérgico en pacientes con dermatitis atópica y dermatitis de las manos. Evaluación del Registro Español de Dermatitis de Contacto (REIDAC).

BACKGROUND: Hand eczema is common in patients with atopic dermatitis (AD), but few studies have described the characteristics of these patients in large, representative populations from different geographic regions and occupational settings. OBJECTIVE: To describe the epidemiological, clinical, and allergy profile of patients with hand eczema who underwent patch testing and compare patients with and without AD. METHODS: Analysis of data from the Spanish Contact Dermatitis Registry, a multicenter registry of patients who undergo patch testing in Spain. RESULTS: We included 1466 patients with hand eczema who were patch tested between January 2018 and June 2020. Those with AD were younger and had had symptoms for longer before testing. They were also more likely to have been exposed to occupational triggers (38% vs 53% for patients without AD). The only profession for which significant differences were found was hairdressing. The most common allergens were nickel sulfate, methylchloroisothiazolinone/methylisothiazolinone, cobalt chloride, potassium dichromate, fragrance mixes I and II, and formaldehyde. The most common diagnoses were allergic contact dermatitis (24% vs 31% in patients with and without AD, P=.0224) and irritant contact dermatitis (18% and 35% respectively, P<.001). CONCLUSIONS: AD is common in patients with predominant hand eczema who undergo patch testing. Patients with hand eczema and AD have different clinical and epidemiological characteristics to hand eczema patients in general and their final diagnosis following patch testing is also different.

Allergic contact dermatitis from acrylic nails in a flamenco guitarist.

Acrylates are molecules that are well known for their strong sensitizing properties. Historically, many beauticians and individuals using store-bought artificial nail products have developed allergic contact dermatitis from acrylates. More recently, the use of acrylic nails among flamenco guitarists to strengthen their nails has become very popular. A 40-year-old non-atopic male patient working as a flamenco guitarist developed dystrophy, onycholysis and paronychia involving the first four nails of his right hand. The lesions were confined to the fingers where acrylic materials were used in order to strengthen his nails to play the guitar. He noticed improvement whenever he stopped using these materials and intense itching and worsening when he began reusing them. Patch tests were performed and positive results obtained with 2-hydroxyethyl methacrylate (2-HEMA), 2-hydroxyethyl acrylate (2-HEA), ethyleneglycol-dimethacrylate (EGDMA) and 2-hydroxypropyl methacrylate (2-HPMA). The patient was diagnosed with occupational allergic contact dermatitis likely caused by acrylic nails. Artificial nails can contain many kinds of acrylic monomers but most cases of contact dermatitis are induced by 2-HEMA, 2-HPMA and EGDMA. This is the first reported case of occupational allergic contact dermatitis from acrylates in artificial nails in a professional flamenco guitar player. Since the practice of self-applying acrylic nail products is becoming very popular within flamenco musicians, we believe that dermatology and occupational medicine specialists should be made aware of the potentially increasing risk of sensitization from acrylates in this setting.

Effect of ß-lactoglobulin A and B whey protein variants on cheese yield potential of a model milk system.

Cheese yield mainly depends on the amount and proportion of milk constituents; however, genetic variants of the proteins present in milk may also have an important effect. The objective of this research was to study the effect of the variants A and B of ß-lactoglobulin (LG) on cheese yield using a model system consisting of skim milk powder fortified with different levels of a mixture containing α-lactalbumin and ß-LG genetic variants (A, B, or A-B) in a 1:2 ratio. Fortified milk samples were subjected to pasteurization at 65 °C for 30 min. Miniature cheeses were made by acidifying (pH=5.9) fortified milk and incubating with rennet for 1h at 32 °C. The clot formed was cut, centrifuged at 2,600 × g for 30 min at 20 °C and drained for determining cheese yield. Cheese-yielding capacity was expressed as actual yield (grams of cheese curd per 100g of milk) and dry weight yield (grams of dried cheese curd per 100g of milk). Free-zone capillary electrophoresis was used for determining ß-LG A or B recovery in the curd during rennet-induced coagulation. The presence of ß-LG variant B resulted in a significantly higher actual and dried weight cheese yield than when A or A-B were present at levels ≤ 0.675% of whey protein (WP) addition. Results of free-zone capillary electrophoresis allowed us to infer that ß-LG B associates with the casein micelles during renneting, as shown by an increase in the recovery of this variant in the curd when ß-LG B was added up to a maximum at 0.45% (equivalent to 0.675% WP). In general, actual or dried weight cheese yield increased as WP addition was increased from 0.225 to 0.675%. However, when WP addition ranged from 0.675 to 0.90%, a drastic drop in cheese yield was observed. This behavior may be because an increase in the aggregation of casein micelles with a concomitant inclusion of whey protein in the gel occurs at low levels of WP addition, whereas once the association of WP with the casein micelles reach a saturation point at addition levels higher than 0.675%, rearrangements of the gel network result in larger whey expulsion and syneresis. This knowledge is expected to be useful to maximize cheese yield and optimize processing conditions during cheese and cheese analogs manufacturing.

The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression.

The Snail family of transcription factors has previously been implicated in the differentiation of epithelial cells into mesenchymal cells (epithelial-mesenchymal transitions) during embryonic development. Epithelial-mesenchymal transitions are also determinants of the progression of carcinomas, occurring concomitantly with the cellular acquisition of migratory properties following downregulation of expression of the adhesion protein E-cadherin. Here we show that mouse Snail is a strong repressor of transcription of the E-cadherin gene. Epithelial cells that ectopically express Snail adopt a fibroblastoid phenotype and acquire tumorigenic and invasive properties. Endogenous Snail protein is present in invasive mouse and human carcinoma cell lines and tumours in which E-cadherin expression has been lost. Therefore, the same molecules are used to trigger epithelial-mesenchymal transitions during embryonic development and in tumour progression. Snail may thus be considered as a marker for malignancy, opening up new avenues for the design of specific anti-invasive drugs.

Thanatophoric dysplasia type II with encephalocele and semilobar holoprosencephaly: Insights into its pathogenesis.

Thanatophoric dysplasia (TD) is a lethal form of short-limb skeletal dysplasia that is associated with macrocephaly, and variably cloverleaf skull. Two types of TD are clinically recognized, TD1 and TD2, mainly distinguished by their radiographic characteristics. The differences between the two are principally observed in the femur, which appears curved in TD1, while it remains straight but with a proximal medial spike in TD2, and are a less severe overall affectation in TD2. Both types of TD are caused by mutations in different functional domains of the FGFR3 gene. However, whereas several mutations in the different domains of FGFR3 cause TD1, the K650E mutation involving the change of a lysine to glutamic acid ("Lys650Glu") has been found in all TD2 cases to date. Here we describe a newborn infant with TD2 associated with brain defects that have either been infrequently observed (encephalocele) or not hitherto described (holoprosencephaly). Based on recent studies, we consider encephaloceles described in TD to be pseudoencephaloceles, since they are secondary to the intracranial pressure generated by severe hydrocephaly and to severe cranial structural anomalies. Finally, to analyze the mechanisms of holoprosencephaly observed in the case described here, we include a concise review on the current understanding of how FGFs and their receptors are expressed in the rostral signaling center (particularly Fgf8). In addition, we evaluated recent observations that FGF ligands and receptors (including FGFR3) act in concert to organize the whole telencephalon activity, rather than independently patterning different areas.

TRIM72 Immunohistochemical Expression Can Predict Relapse in Colorectal Carcinoma.

Large bowel adenocarcinoma is one of the most frequent human neoplasms and despite recent insights into the pathophysiology and molecular basis of this disease, mortality remains high in advanced and metastatic cases. Most guidelines recommend adjuvant chemotherapy for tumours involving lymph nodes, but not for patients with localized stage I or II disease. However, it is well known that approximately 20% of stage II colorectal carcinoma patients eventually recur, mainly with distant or peritoneal involvement and show bad prognosis. It would be important to predict which patients are at increased risk of recurrence to guide potential adjuvant therapy use in this controversial setting. In this sense, only microsatellite stability has been proposed as a predictive tool in some guidelines. The tripartite motif family protein 72 (TRIM72) is a ubiquitin ligase, involved in the cell membrane repair machinery and known to be associated to insulin resistance. Its potential role in colon cancer has recently been proposed. The aim of this study is to determine the potential predictive value of TRIM72 immunohistochemical expression in stage II colon carcinoma. We have retrospectively reviewed a series of 95 patients with stage II colon microsatellite stable carcinomas operated with a curative intent at a single large tertiary hospital in Madrid (Spain) between 2006 and 2012. None of the patients received adjuvant chemotherapy. We reviewed the histopathological slides and constructed a tissue microarray (TMA) of three representative areas to perform immunohistochemical staining for TRIM72. In our series 30 patients (31.7%) recurred after a median follow-up of 17.5 months. Lack of immunohistochemical expression of TRIM72 in the tumor was significantly and independently associated to recurrence. A recent report by Chen et al. has shown that TRIM72 can be measured in plasma for colon carcinoma detection as an alternative to CEA or CA19.9, with lower levels in patients with carcinoma. Our report is the first one to show that lower immunohistochemical expression of TRIM72 predicts recurrence in colon stage II carcinoma. We feel this predictive influence can be related to its crucial role as a central regulator in many signaling pathways (PI3K-AKT, ERK). As an ubiquitin ligase, the lack of TRIM72 could increase the levels of several potential oncogenic molecules and therefore lead to a more aggressive phenotype. It remains to be shown whether chemotherapy could change the clinical behaviour of this bad prognosis group. We propose TRIM72 immunohistochemical analysis as a potential tool to predict recurrence risk in stage II colon carcinoma patients. Our results should be confirmed in larger series, but could open the way to management strategies refinement in this early stage group of patients.

Patch Testing During the COVID-19 Pandemic: Recommendations of the AEDV's Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC). / Recomendaciones del Grupo Español de Investigación en Dermatitis de Contacto y Alergia Cutánea (GEIDAC) de la AEDV en relación con la realización de pruebas epicutáneas durante la pandemia por SARS-CoV-2 (COVID-19).

As the COVID-19 pandemic gradually comes under control, the members of the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) have drawn up a proposed list of the requirements, limitations, and conditioning factors affecting the resumption of work in contact dermatitis units. The assumption is that the severe acute respiratory syndrome coronavirus2 is still circulating and that occasional or seasonal outbreaks will occur. They recommend that the first step should be to assess how many patch tests each clinic can handle and review the waiting list to prioritize cases according to disease severity and urgency. Digital technologies can, where possible, be used to send and receive the documentation necessary for the patch test (information, instructions, informed consent, etc.). If the necessary infrastructure is available, patients can be offered the option of a remote initial consultation. Likewise, in selected cases, the patch test results can be read in a virtual visit using photographs taken by the patient or a video visit can be scheduled to allow the physician to evaluate the site of application remotely. These measures will reduce the number of face-to-face visits required, but will not affect the time spent on each case, which must be scheduled in the normal manner. All of these recommendations are suggestions and should be adapted to the needs and possibilities of each health centre.

Control of cell behavior during vertebrate development by Slug, a zinc finger gene.

Slug, a vertebrate gene encoding a zinc finger protein of the Snail family, is expressed in the neural crest and in mesodermal cells emigrating from the primitive streak. Early chick embryos were incubated with antisense oligonucleotides to chick Slug. These oligonucleotides specifically inhibit the normal change in cell behavior that occurs at the two sites in the emerging body plan in which the gene is expressed. This change, which is the transition from epithelial to mesenchymal character, occurs at the formation of mesoderm during gastrulation and on emigration of the neutral crest from the neural tube.

Rivality index neighbourhood algorithm with density and distances weighted schemes for the building of robust QSAR classification models with high reliable applicability domain.

The rivality index (RI) is a normalized distance measurement between a molecule and their first nearest neighbours providing a robust prediction of the activity of a molecule based on the known activity of their nearest neighbours. Negative values of the RI describe molecules that would be correctly classified by a statistic algorithm and, vice versa, positive values of this index describe those molecules detected as outliers by the classification algorithms. In this paper, we have described a classification algorithm based on the RI and we have proposed four weighted schemes (kernels) for its calculation based on the measuring of different characteristics of the neighbourhood of molecules for each molecule of the dataset at established values of the threshold of neighbours. The results obtained have demonstrated that the proposed classification algorithm, based on the RI, generates more reliable and robust classification models than many of the more used and well-known machine learning algorithms. These results have been validated and corroborated by using 20 balanced and unbalanced benchmark datasets of different sizes and modelability. The classification models generated provide valuable information about the molecules of the dataset, the applicability domain of the models and the reliability of the predictions.

Cell movements during vertebrate development: integrated tissue behaviour versus individual cell migration.

Cell migration during development is fundamental to the establishment of the embryonic architecture. Depending on the context, cells may move either as integrated sheets of tissue or individually. Recently, molecules that are involved in both these types of cell behaviour have been identified, helping us to understand developmental processes as important as gastrulation and neural crest formation, and ultimately, the morphogenetic movements that shape the embryo.

Robust QSAR prediction models for volume of distribution at steady state in humans using relative distance measurements.

The building of quantitative structure-activity relationship (QSAR) models for the in silico prediction of volume distribution for drugs at steady-state levels is vital for the selection of potential drugs at the synthesis stage. Using molecular descriptor matrixes, some regression models presenting low accuracy have been proposed, mainly due to the difficulty of compiling an appropriate dataset and the lack of information on dataset representation. In this paper, we use a benchmark dataset of very diverse drugs for the development of predictive models for volume distribution based on the use of relative distance matrixes as the input data to QSAR algorithms. Support vector machine, complex tree, bagged tree and Gaussian process regression algorithms were tested for fingerprint, similarity and relative distance matrixes used as input data, and the results of the built models were compared. Relative distance matrixes generated robust regression models in the training and external validation stages performed using cross-validation, obtaining values for correlation coefficient, bias, slope and root-mean-square error close to the ideal. Relative distance matrixes were also used for the design of classification models, obtaining excellent results with values of accuracy and area under receiver operating characteristic (AUC) close to 100%.

QSAR classification and regression models for ß-secretase inhibitors using relative distance matrices.

The development of robust QSAR models to predict the activity of molecules of ß-secretase inhibitors is an area of interest due to the increase of Alzheimer's disease in patients in the global population. In this paper, we present a proposal based on the use of relative distance matrices as input data to the QSAR algorithms. These matrices store measurements of distances between the structural characteristics of pairs of molecules and between the molecules and a structural pattern extracted from the whole data set, thus efficiently representing a correlation between structural changes and activity. For the building of the classification and regression models support vector machine, tree complex and Gaussian process algorithms have been used; and for the validation of the models cross-validation, bootstrapping and y-randomizing techniques have been applied. The results obtained are close to 100% in accuracy and area under receiver operating characteristic values in classification, and close to 1.0 for r2 and 0.1 for root mean square error in regression in training and in external validation, proving the 'goodness' of the proposal.