A real-life ImmunoCAT study: impact of molecular diagnosis through ImmunoCAPTM ISAC 112 on immunotherapy prescription in pollen-polysensitized patients in Catalonia, Spain.

BACKGROUND: Molecular diagnosis in allergology helps to identify multiple allergenic molecules simultaneously. The use of purified and/or recombinant allergens increases the accuracy of individual sensitization profiles in allergic patients. OBJECTIVE: To assess the impact of molecular diagnosis through the ImmunoCAPTM ISAC 112 microarray on etiological diagnosis and specific immunotherapy (SIT) prescription. This was compared to the use of conventional diagnoses in pediatric, adolescent, and young adult patients with rhinitis or rhinoconjunctivitis and/or allergic asthma, sensitized to three or more pollen allergens of different botanical species. METHODS: A multicenter, prospective, observational study was conducted in patients aged 3-25 years who received care at the Allergology service of 14 hospitals in Catalonia from 2017 to 2020. Allergology diagnosis was established based on the patient's clinical assessment and the results of the skin prick test and specific immunoglobulin E assays. Subsequently, molecular diagnosis was conducted using ImmunoCAPTM ISAC® 112 to recombinant and/or purified allergen components. RESULTS: A total of 109 patients were included; 35 (32.1%) were pediatric patients and 74 (67.9%) were adolescents or young adults (mean age: 18 years), with 58.0% being females. A change of 51.0% was observed in SIT prescription following molecular etiological diagnosis by means of a multi-parameter microarray. CONCLUSIONS: Molecular diagnosis by means of multi-parameter tests increases the accuracy of etiological diagnosis and helps to define an accurate composition of SIT.

Impact of house dust mite-driven asthma on children's school performance and activity.

Evidence regarding asthma's impact on children's daily lives is limited. This prospective and cross-sectional, observational, multicenter study assessed school/work and activity impairment in children and adolescents with allergic asthma and their caregivers and allergen immunotherapy (AIT) effects. Included patients were schooled children and adolescents (5 to 17 years) with allergic asthma due to house dust mites (HDM). Impairment of school/work (i.e., absenteeism and presenteeism) and activity was measured in patients and their caregivers using the Work Productivity Impairment Questionnaire plus Classroom Impairment Questions: Allergy Specific (WPAI + CIQ:AS). HDM allergic patients with school impairment received subcutaneous AIT with a MicroCrystalline Tyrosine-associated allergoid. WPAI + CIQ:AS and effectiveness variables were compared between baseline and 1-year post-AIT. Of the 113 patients included, 59 (52.2%) and 51 (45.1%) showed school and activity impairment, respectively, missing a mean (SD) of 37.6 (24.4) % and 42.6 (25.6) % of school and activity time, respectively. Twenty-six (23%) caregivers reported activity impairment and, of the 79 (69.9%) employed, 30 (38%) reported work impairment. Of the 65 patients with school/activities impairment, 41 (63.1%) received AIT, of which 21 (51.2%) completed 1 year of treatment. Effectiveness variables and WPAI + CIQ:AS significantly improved: Mean (SD) school impairment decreased from 39.7 (26.7) to 2.1 (7.1) % (p < 0.001) and activity impairment from 46.2 (34.6) to 1.4 (3.6) % (p < 0.001). CONCLUSION: Allergic asthma due to HDMs results in school/work and activity impairment in children and adolescents and their caregivers. One year of AIT provided clinical benefits and reduced school and activity impairment. WHAT IS KNOWN: • Allergic asthma impairs children's school performance and daily activities. • Allergen immunotherapy modifies allergic disease course and ameliorates its symptoms. WHAT IS NEW: • Asthma symptoms due to allergy to house dust mites impair children's school attendance and productivity and daily activity and their caregivers' work performance and daily lives. • Allergen immunotherapy with a house dust mite MicroCrystalline Tyrosine (MCT)-associated allergoid seems to provide clinical benefits, associated with decreased school and activity impairment, supporting it as an effective treatment option.

Autologous Cultured Bone Marrow-Derived Mesenchymal Stem Cells in a Fibrin Spray to Treat Venous Ulcers: A Randomized Controlled Double-Blind Pilot Study.

We treated a small cohort of venous ulcers that were very unresponsive to standard and advanced therapies with autologous cultured bone marrow-derived mesenchymal stem cells (MSCs). This pilot clinical trial was randomized, controlled, and double-blinded. Subjects were treated with either normal saline (Group A), fibrin spray alone (Group B), or MSCs in fibrin (1 million cells/cm2 of wound bed surface) (Group C). The control and test materials were applied to the wound using a double-barreled syringe with thrombin and fibrinogen (with or without MSCs) in each barrel, or saline alone in both barrels. The MSCs were separated, cultured in vitro, and expanded in a dedicated Good Manufacturing Practice (GMP) facility from 30-50 ml of bone marrow aspirate obtained from the iliac crest in Group C subjects. To ensure that the study remained controlled and blinded, subjects who were randomized to one of the two control arms (saline or fibrin) underwent sham bone marrow aspiration performed by a hematologist who anesthetized the iliac crest area down to and pushing against the periosteum, but without penetrating the bone marrow. Therefore, both the clinician who evaluated wound progress and the study subjects had no knowledge of whether bone aspiration was actually performed and what treatment had been applied to the wound. The study was performed after full FDA investigational new drug (IND) approval. The primary endpoint was the rate of healing (wound closure as linear healing from the wound margins in cm/week), as measured by the Gilman equation. One-way ANOVA was used to calculate the statistical significance of differences between the mean healing rates of each of the 3 treatment groups every 4 weeks and over the 24 weeks of treatment. Overall, treatment with MSCs accelerated the healing rate by about 10-fold compared to those in the saline and fibrin control groups. Although the total number of patients in this pilot study was small (n=11), the statistical significance was surprisingly promising: p<0.01 and f-ratio of 15.9358. No serious adverse events were noted. This small but carefully performed prospective, controlled, randomized, and double-blinded pilot study in a rare population of totally unresponsive patients adds to previous reports showing the promise of MSCs in the treatment of chronic wounds and provides proof of principle for how to approach this type of very demanding clinical and translational research.

Assessment of frailty in elderly patients attending a multidisciplinary wound care centre: a cohort study.

BACKGROUND: The incidence of frailty and non-healing wounds increases with patients' age. Knowledge of the relationship between frailty and wound healing progress is greatly lacking. METHODS: The aim of this study is to characterize the degree of frailty in elderly patients attending a multidisciplinary wound care centres (MWCC). Additionally, we seek to assess the impact of frailty on the wound healing rate and wound healing time. An open cohort study was conducted on 51 consecutive patients aged > 70 years treated for wounds at an MWCC of an intermediate care hospital. The frailty score was determined according to the Frail-VIG index. Data were collected through patient questionnaires at the beginning of the study, and at 6 months or upon wound healing. Wounds were followed up every 2 weeks. To analyse the relationship between two variables was used the Chi-square test and Student's or the ANOVA model. The t-test for paired data was used to analyse the evolution of the frailty index during follow-up. RESULTS: A total of 51 consecutive patients were included (aged 81.1 ± 6.1 years). Frailty prevalence was 74.5% according to the Frail-VIG index (47.1% mildly frail, 19.6% moderately frail, and 7.8% severely frail). Wounds healed in 69.6% of cases at 6 months. The frailty index (FI) was higher in patients with non-healing wounds in comparison with patients with healing wounds (IF 0.31 ± 0.15 vs IF 0.24 ± 0.11, p = 0.043). A strong correlation between FI and wound healing results was observed in patients with non-venous ulcers (FI 0.37 ± 0.13 vs FI 0.27 ± 0.10, p = 0.015). However, no correlation was observed in patients with venous ulcers (FI 0.17 ± 0.09 vs FI 0.19 ± 0.09, p = 0.637). Wound healing rate is statically significantly higher in non-frail patients (8.9% wound reduction/day, P25-P75 3.34-18.3%/day;AQ6 p = 0.044) in comparison with frail patients (3.26% wound reduction/day, P25-P75 0.8-8.8%/day). CONCLUSION: Frailty is prevalent in elderly patients treated at an MWCC. Frailty degree is correlated with wound healing results and wound healing time.

Dermal Fibroblasts from Chronic Wounds Exhibit Paradoxically Enhanced Proliferative and Migratory Activities that May be Related to the Non-Canonical Wnt Signaling Pathway.

It is generally thought that dermal fibroblasts from chronic wounds are in a state of senescence, which contributes to the failure to heal. This assumption, based on limited experimental evidence, has led to the widespread use of therapeutic approaches focused on delivering new fibroblasts and/or increasing resident fibroblast activity to promote healing. In this study, we decided to re-visit the evidence for the relative inactivity of resident chronic wound fibroblasts. We therefore evaluated the proliferative and migratory activities of matching, patient-derived dermal fibroblasts from a chronic wound (wound dermal fibroblasts, or WDF), ipsilateral thigh newly created acute wound dermal fibroblasts (ADF, Day-3 after wounding the normal thigh skin), and ipsilateral thigh normal dermal skin fibroblasts (NDF). This approach was used in each of 10 consecutive non-selected individual patients with a venous leg ulcer, and allowed us to determine whether WDF are intrinsically less active than NDF and AWD. Cell migration and proliferation were quantified by a live-cell analysis system and MTT assay, respectively, in low (0.5%) or high (10%) levels of fetal bovine serum (FBS). In addition, the ability of patient-derived fibroblasts to modulate wound re-epithelialization in vivo was analyzed by transplantation in a mouse tail full-thickness wound model. Wnt5a mRNA, its ROR1 co-receptors, and ROR2 mRNA levels were determined by qRT-PCR. We report that WDF had increased -SMA and increased levels of Wnt5a. Moreover, using live-cell imaging in a scratch assay monolayer model, WDF showed baseline migratory activity similar to those of NDF and ADF, and such activity was not stimulated by FBS. WDF showed the same capacity to increase wound re-epithelialization as NDF and ADF. Together, these results suggest that WDF are not actually less "active" than NDF and ADF. This enhanced activity of chronic wound fibroblasts may lead to high energy requirements that contribute to a failure to heal. The findings may represent a new paradigm for wound chronicity, impaired healing, and high recurrence rates.

A toolkit for the quantitative evaluation of chronic wounds evolution for early detection of non-healing wounds.

BACKGROUND: Chronic wounds resulting from a number of conditions do not heal properly and can pose serious health problems. Beyond clinician visual inspection, an objective evaluation of the wound is required to assess wound evolution and the effectiveness of therapies. AIM: Our objective is to provide a methodology for the analysis of wound area vs. time for the early prediction of non-healing wounds evolution. METHODS: We propose a two-step approach consisting of: i) wound area quantification from planimetries and ii) classification of wound healing through the inference of characteristic parameters. For the first step, we describe a user-friendly software (Woundaries) to automatically calculate the wound area and other geometric parameters from hand-traced planimetries. For the second, we use a procedure for the objective classification of wound time evolution and the early assessment of treatment efficacy. The methodology was tested on simulations and retrospectively applied to data from 85 patients to compare the effect of a biological therapy with respect to general basic therapeutics. RESULTS: Woundaries provides measurements of wound surface equivalent to a validated device. The two-step methodology allows to determine if a wound is healing with high sensitivity, even with limited amount of data. Therefore, it allows the early assessment of the efficacy of a therapy. CONCLUSION: The performance of this methodology for the quantification and the objective evaluation of wound area evolution suggest it as a useful toolkit to assist clinicians in the early assessment of the efficacy of treatments, leading to a timely change of therapy.

Meibomian gland dysfunction (MGD), as diagnosed by non-contact infrared Meibography, in dogs with ocular surface disorders (OSD): a retrospective study.

BACKGROUND: Meibomian gland dysfunction (MGD) is one of the possible conditions underlying ocular surface disorders (OSD). Prevalence of MGD in dogs affected by OSD has not yet been reported. We aimed to evaluate the prevalence of MGD among OSD canine patients, which had been assessed by non-contact infrared meibography and interferometry, and to identify MGD associated factors that might guide its diagnosis. Medical records of canine patients examined for OSD between 2016 and 2019 were reviewed. The frequency of MGD was evaluated within different categories (skull conformation, gender, eye and STT-1). The putative MGD risk factors and frequency of MGD within grades of interferometry were evaluated in a regression analysis model and reported as odd ratios (ORs). RESULTS: One hundred fifty eyes from 81 dogs with OSD were included with median age 75 months (range 3-192) and female representation with 52%. MGD was present in 70% of the examined eyes. MGD risk was higher in males ORadj = 3.015 (95% CI: 1.395-6.514) (P = 0.005) and older patients ORadj = 1.207 (95% CI: 1.081-1.348) (P = 0.001). No significant differences were found between left and right eyes (P = 0.66) or between the two types of skull conformation (P = 0.477) and MGD presence. MGD was associated to the lowest lipid layer (LL) thickness, as assessed by interferometry (grade 0) OR = 16.00 (95% CI: 2.104-121.68) (P < 0.001). STT values were not significantly associated with the presence of MGD (P > 0.05). CONCLUSIONS: MGD is a common underlying pathology in OSD. Being male and higher age are risk factors for MGD. An interferometry grade 0 may guide OSD diagnosis towards MGD.

Incidence and characteristics of uncommon dementia subtypes: Results from 10 years of clinical surveillance by the Registry of Dementia of Girona.

INTRODUCTION: Age- and sex-stratified incidence rates of uncommon dementia subtypes are imprecise and scarce. METHODS: We used data from 7357 newly diagnosed individuals aged between 30.6 and 101.0 years from the Registry of Dementia of Girona during 2007-2016 to determine the incidence rates of uncommon dementia subtypes stratified by sex and age groups and to describe their clinical characteristics. RESULTS: Uncommon dementia subtypes were classified according to their etiology. The incidence rate of uncommon dementia subtypes was 27.8 cases per 100,000 person-years for those aged 30 years and older, 3.7 cases per 100,000 person-years for people aged less than 65 years, and 110.9 per 100,000 person-years for those aged 65 years and older. Age, sex, dementia severity, and medical comorbidities were different depending on the dementia subtype. DISCUSSION: There are differences in the incidence rates and the demographic and clinical characteristics among uncommon dementia subtypes for age and sex groups.

Bilateral phacoemulsification and intraocular lens implantation in a young African lion (Panthera leo).

An 18-month-old intact female lioness (Panthera leo) was referred to the Clinica Veterinaria Roma Sud for evaluation of bilateral cataracts. Phacoemulsification and implantation of +30 diopter intraocular lens (IOL) were performed bilaterally. Seven years after surgery, the IOL remained centrally positioned and the patient had normal activity.

Phaco-émulsification bilatérale et implantation d'une lentille intra-oculaire chez une jeune lionne africaine (Panthera leo) . Une lionne entière âgée de 18 mois (Panthera leo) a été dirigée à la Clinica Veterinaria Roma Sud pour l'évaluation de cataractes bilatérales. La phaco-émulsification et l'implantation de lentilles intraoculaires dioptriques +30 (LID) ont été réalisées bilatéralement. Sept années après la chirurgie, les LID sont demeurées en position centrale et la patiente s'adonnait à des activités normales.(Traduit par Isabelle Vallières).

Transforming growth factor beta (TGF-ß) isoforms in wound healing and fibrosis.

Scar formation, with persistent alteration of the normal tissue structure, is an undesirable and significant result of both wound healing and fibrosing disorders. There are few strategies to prevent or to treat scarring. The transforming growth factor beta (TGF-ß) superfamily is an important mediator of tissue repair. Each TGF-ß isoform may exert a different effect on wound healing, which may be context-dependent. In particular, TGF-ß1 may mediate fibrosis in adults' wounds, while TGF-ß3 may promote scarless healing in the fetus and reduced scarring in adults. Thus, TGF-ß3 may offer a scar-reducing therapy for acute and chronic wounds and fibrosing disorders.

Rate of dementia diagnoses according to the degree of aging of the population.

BACKGROUND: There is a lack of information regarding geographical differences in the incidence and prevalence of dementia diagnosis according to the degree of aging of the population. The objectives of this study were to analyze the rate of dementia diagnoses, and to compare the dementia subtypes and the clinical characteristics of the patients depending on the degree of aging of their municipalities. METHODS: We used data from the Registry of Dementias of Girona (ReDeGi), containing the cases of dementia diagnosed in the memory clinics of the Health Region of Girona, in Catalonia (Spain), during 2007-2012. The municipalities were classified by a cluster analysis as aged or young municipalities according to their proportion of older people using population ageing indicators. The incidence rates of dementia diagnosis in each type of municipality were compared. RESULTS: The ReDeGi registered 4,314 cases in the municipalities under surveillance. The clinical incidence of dementia was lower in aged municipalities (4.5 vs. 6.1 cases per 1,000 person-years aged 65 and over). Patients from young municipalities had an increased frequency of behavioral and psychological symptoms of dementia. CONCLUSIONS: The environment may influence the clinical manifestations of dementia that predispose people to visit health specialists and obtain a diagnosis.

Inhibition of the CoREST Repressor Complex Promotes Wound Re-Epithelialization through the Regulation of Keratinocyte Migration.

Wound healing is a complex process involving phases of hemostasis, inflammation, proliferation, and remodeling. The regenerative process in the skin requires coordination between many regulators, including signaling molecules, transcription factors, and the epigenetic machinery. In this study, we show that chromatin regulators HDAC1 and LSD1, key components of the CoREST repressor complex, are upregulated in the regenerating epidermis during wound repair. We also show that corin, a synthetic dual inhibitor of the CoREST complex and HDAC1/LSD1 activities, significantly accelerates wound closure through enhanced re-epithelialization in a mouse tail wound model. Acetylated H3K9 (methylation of histone H3 at lysine 9) expression, a histone modification targeted by HDAC1, is increased in keratinocytes after topical treatment with 100 nM and 1 µM of corin. In vitro experiments demonstrate that corin promotes migration and inhibits the proliferation of human keratinocytes. Furthermore, expression levels of genes promoting keratinocyte migration, such as AREG, CD24, EPHB2, ITGAX, PTGS, SCT1, SERPINB2, SERPINE1, SLPI, SNAI2, and TWIST, increased in keratinocytes treated with corin. These data demonstrate that dual inhibition of class I histone deacetylases and LSD1 by corin may serve as a new approach for promoting wound re-epithelialization and provide a platform for further applications of corin for the treatment of chronic wounds.

Medication Assessment in an Older Population during Acute Care Hospitalization and Its Effect on the Anticholinergic Burden: A Prospective Cohort Study.

(1) Background: Anticholinergic and sedative drugs (ASDs) contribute to negative health outcomes, especially in the frail population. In this study, we aimed to assess whether frailty increases with anticholinergic burden and to evaluate the effects of medication reviews (MRs) on ASD regimens among patients attending an acute care for the elderly (ACE) unit. (2) Methods: A cohort study was conducted between June 2019 and October 2020 with 150 consecutive patients admitted to our ACE unit. Demographic, clinical, and pharmacological data were assessed. Frailty score was determined using the Frail-VIG index (FI-VIG), and ASD burden was quantified using the drug burden index (DBI). In addition, the MR was performed using the patient-centered prescription (PCP) model. We used a paired T-test to compare the DBI pre- and post-MR and univariate and multivariate regression to identify the factors associated with frailty. (3) Results: Overall, 85.6% (n = 128) of participants showed some degree of frailty (FI-VIG > 0.20) and 84% (n = 126) of patients received treatment with ASDs upon admission (pre-MR). As the degree of frailty increased, so did the DBI (p < 0.001). After the implementation of the MR through the application of the PCP model, a reduction in the DBI was noted (1.06 ± 0.8 versus 0.95 ± 0.7) (p < 0.001). After adjusting for covariates, the association between frailty and the DBI was apparent (OR: 11.42, 95% (CI: 2.77-47.15)). (4) Conclusions: A higher DBI was positively associated with frailty. The DBI decreased significantly in frail patients after a personalized MR. Thus, MRs focusing on ASDs are crucial for frail older patients.

Utility of human epididymis protein 4 in the differential diagnosis of ascites.

BACKGROUND AND AIMS: Human epididymal protein 4 (HE4) may be a useful tool in the differential diagnosis of malignant ascites. The aim of this study was to evaluate the diagnostic utility of HE4 for detecting malignant ascites, taking into account the possible false positives identified with adenosine deaminase (ADA), C-reactive protein (CRP), % polynuclear cells (%PMN) and glomerular filtration rate (eGFR). METHODS: Concentrations of HE4, ADA, %PMN and CRP were determined in 114 samples of peritoneal fluid and creatinine in serum in order to calculate eGFR. RESULTS: Concentrations of HE4 presented significant differences (P = 0.028) in benign [median (interquartile range)] [582(372)] pmol/L) and malignant ascites ([8241(367)] pmol/L. Sensitivity was 21.2% and specificity 100%. Significant differences were also observed for HE4 between tumors of gynecological origin ([3165(8769)] pmol/L) and others ([665(663)] pmol/L), with a sensitivity of 67% and a specificity of 100%. Classifying according to possible false positives (ADA > 45U/L, CRP > 50 mg/L, %PMN > 90 and eGFR < 30 mL/min/1.73 m2) at maximum specificity, a sensitivity of 33.3% was obtained for HE4, with a cut-off point of 2660 pmol/L. Without possible false positives (ADA < 45U/L, CRP < 50 mg/L, %PMN < 90 and eGFR ≥ 30 mL/min/1.73 m2), a sensitivity of 37.7% was obtained at 100% specificity for a cut-off point of 1041 pmol/L. Applying these criteria to the entire group, a sensitivity of 36.4% was obtained at maximum specificity. CONCLUSIONS: HE4 allows the identification of malignant ascites with moderate sensitivity at maximum specificity. HE4 levels can differentiate between tumors of gynecological origin and others. Classification according to possible false positives increases sensitivity without losing specificity.

Profile and variables related to antipsychotic consumption according to dementia subtypes.

BACKGROUND: Antipsychotics (APs) are usually prescribed to deal with behavioral and psychological symptoms of dementia (BPSD), but poor outcomes, important side effects, and high mortality risk should be addressed. The aim of this study was to estimate the prevalence of AP consumption in patients with dementia, and to describe and compare the sociodemographic and clinical characteristics of patients consuming APs. METHODS: This was a cross-sectional study using 1,894 cases of dementia registered from 2007 to 2009 by the Registry of Dementias of Girona (ReDeGi), which is a population-based passive surveillance system of dementia diagnoses. APs were categorized according to the anatomical therapeutic chemical (ATC) classification, and grouped as typical antipsychotics (TAPs) or atypical antipsychotics (AAPs). Binary logistic regression analyses were used to detect the predictors of AP use as well as the variables associated with TAP or AAP prescription. RESULTS: APs were used in 29.6% of the cases, with Parkinsonian syndromes (PSd) being the subtype of dementia with the highest AP prescription (50.6% of the patients with PSd). AAPs were mainly prescribed in all subtypes of dementia, except in vascular dementia (VaD) and PSd, where no preference in TAP or AAP use was found. Psychotic antecedents, dementia with Lewy bodies (DLB) diagnoses, cognitive impairment, and BPSD were AP use predictors. AAP use was related to higher severity of dementia. CONCLUSIONS: Despite their disputed benefit-risk ratios, APs are extensively used, off-label, to treat BPSD, and AAPs are more commonly prescribed than TAPs. AP consumption was frequent in DLB, and was related to dementia severity indicators.

Convolutional Neural Network for Skin Lesion Classification: Understanding the Fundamentals Through Hands-On Learning.

Deep learning architectures for the classification of images have shown outstanding results in a variety of disciplines, including dermatology. The expectations generated by deep learning for, e.g., image-based diagnosis have created the need for non-experts to become familiar with the working principles of these algorithms. In our opinion, getting hands-on experience with these tools through a simplified but accurate model can facilitate their understanding in an intuitive way. The visualization of the results of the operations performed by deep learning algorithms on dermatological images can help students to grasp concepts like convolution, even without an advanced mathematical background. In addition, the possibility to tune hyperparameters and even to tweak computer code further empower the reach of an intuitive comprehension of these processes, without requiring advanced computational and theoretical skills. This is nowadays possible thanks to recent advances that have helped to lower technical and technological barriers associated with the use of these tools, making them accessible to a broader community. Therefore, we propose a hands-on pedagogical activity that dissects the procedures to train a convolutional neural network on a dataset containing images of skin lesions associated with different skin cancer categories. The activity is available open-source and its execution does not require the installation of software. We further provide a step-by-step description of the algorithm and of its functions, following the development of the building blocks of the computer code, guiding the reader through the execution of a realistic example, including the visualization and the evaluation of the results.

Urticaria and silent parasitism by Ascaridoidea: Component-resolved diagnosis reinforces the significance of this association.

Urticaria remains a major problem in terms of aetiology, investigation, and management, and although parasitic diseases are considered potential causes, the absence of a consistent link between parasitic infections and skin allergy symptoms leads to the need for a deeper study of parameters that support this association. The objectives of this study were to analyse a possible relationship between parasitism by Ascarididae (Toxocara canis and Anisakis simplex) and the clinical expression of urticaria and to identify possible parasitic molecular markers for improving the diagnosis of unknown urticaria aetiology. The prevalence of Toxocara and Anisakis infestations was evaluated by measuring the levels of specific IgG (sIgG) and IgE (sIgE) antibodies against crude extracts and isolated components from whole larvae of Anisakis simplex (Ani s 1, Ani s 3 and Ani s 7) and Toxocara canis (TES-120, TES-70, TES-32 and TES-26) using immunologic and molecular diagnostic methods. A cross-sectional study was performed in a group of 400 individuals. The study group consisted of 95 patients diagnosed with urticaria (55 with chronic urticaria and 40 with acute urticaria). A control group consisted of 305 subjects without urticaria (182 diagnosed with respiratory allergy and 123 without allergy). Statistically significant differences were demonstrated in the seroprevalence of specific IgG and IgE antibodies between the urticaria patients and the healthy general population when isolated ascarid antigens were evaluated. The prevalence of IgG antibodies against Ani s 1, IgE antibodies against TES-120 and IgE antibodies against TES-70 were significantly different between the control individuals (healthy general population) and patients with urticaria. Moreover, the urticaria patient group demonstrated a higher seroprevalence of antibodies (sIgE and sIgG) against Anisakis simplex larva whole extract than the control group but just with statistically diferences when sIgE was evaluated. The presence of IgE and/or IgG antibodies against Ani s 3 (tropomyosin) can help to discriminate between patients with and without urticaria. Both ascarids seem to be associated with urticaria, although in our region, Anisakis seems to have greater involvement than Toxocara in this relationship. Molecular diagnostics can be used to associate urticaria with parasite infestations. Tropomyosin and Ani s 1 were the most relevant markers to demonstrate the association between urticaria and the most relevant Ascarididae parasites in our region.

Research Techniques Made Simple: Deep Learning for the Classification of Dermatological Images.

Deep learning is a branch of artificial intelligence that uses computational networks inspired by the human brain to extract patterns from raw data. Development and application of deep learning methods for image analysis, including classification, segmentation, and restoration, have accelerated in the last decade. These tools have been progressively incorporated into several research fields, opening new avenues in the analysis of biomedical imaging. Recently, the application of deep learning to dermatological images has shown great potential. Deep learning algorithms have shown performance comparable with humans in classifying skin lesion images into different skin cancer categories. The potential relevance of deep learning to the clinical realm created the need for researchers in disciplines other than computer science to understand its fundamentals. In this paper, we introduce the basics of a deep learning architecture for image classification, the convolutional neural network, in a manner accessible to nonexperts. We explain its fundamental operation, the convolution, and describe the metrics for the evaluation of its performance. These concepts are important to interpret and evaluate scientific publications involving these tools. We also present examples of recent applications for dermatology. We further discuss the capabilities and limitations of these artificial intelligence-based methods.

Photoswitchable Antagonists for a Precise Spatiotemporal Control of ß2-Adrenoceptors.

ß2-Adrenoceptors (ß2-AR) are prototypical G-protein-coupled receptors and important pharmacological targets with relevant roles in physiological processes and diseases. Herein, we introduce Photoazolol-1-3, a series of photoswitchable azobenzene ß2-AR antagonists that can be reversibly controlled with light. These new photochromic ligands are designed following the azologization strategy, with a p-acetamido azobenzene substituting the hydrophobic moiety present in many ß2-AR antagonists. Using a fluorescence resonance energy transfer (FRET) biosensor-based assay, a variety of photopharmacological properties are identified. Two of the light-regulated molecules show potent ß2-AR antagonism and enable a reversible and dynamic control of cellular receptor activity with light. Their photopharmacological properties are opposite, with Photoazolol-1 being more active in the dark and Photoazolol-2 demonstrating higher antagonism upon illumination. In addition, we provide a molecular rationale for the interaction of the different photoisomers with the receptor. Overall, we present innovative tools and a proof of concept for the precise control of ß2-AR by means of light.

A clinical registry of dementia based on the principle of epidemiological surveillance.

BACKGROUND: Traditional epidemiological studies do not allow elucidating the reality of referral and diagnosis patterns of dementia in routine clinical practice within a defined territory. This information is useful and necessary in order to plan and allocate healthcare resources. This paper presents the results from a dementia case registry based on epidemiological surveillance fundamentals. METHODS: Standardised registry of dementia diagnoses made in 2007 by specialised care centres in the Health Region of Girona (RSG) (Spain), which encompasses an area of 5,517 sq. km and a reference population of 690,207 inhabitants. RESULTS: 577 cases of dementia were registered, of which 60.7% corresponded to cases of Alzheimer's disease. Presenile dementia accounted for 9.3% of the cases. Mean time between the onset of symptoms and clinical diagnosis was 2.4 years and the severity of the dementia was mild in 60.7% of the cases. High blood pressure, a family history of dementia, dislipidemia, and a past history of depression were the most common conditions prior to the onset of the disease (>20%). CONCLUSION: The ReDeGi is a viable epidemiological surveillance device that provides information about the clinical and demographic characteristics of patients diagnosed with dementia in a defined geographical area.