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Sensory evaluation combined with neuromarketing is expected to improve the understanding of consumer behavior during food tasting. In this study, we used functional near-infrared spectroscopy (fNIRS) to monitor neuronal activation in the prefrontal cortex in response to basic tastes (sweet and bitter) and hedonically different chocolates (whole-milk chocolate and dark chocolate) in 34 healthy consumers. Sweet and bitter tastes tend to elicit decreased and increased neuronal activity, respectively. However, no significant differences in neuronal activation related to different sensitivities to basic tastes were observed. Regarding hedonic neuronal reactions, we detected a significant difference in brain activity between Likers and Dislikers for both chocolates, but the results were inconsistent between the two chocolates. Due to the small sample size, generalizing our results is critical, but these findings suggest that fNIRS could potentially be applied to predict consumer preferences for food, necessitating further research with larger sample sizes.

Abstract Introduction Dupilumab has significantly improved the signs, symptoms and quality of life (QoL) of patients with moderate-to-severe atopic dermatitis (AD) in randomised, controlled clinical trials. However, there is a need to assess the effectiveness and safety of dupilumab in real-world clinical practice. The PROLEAD study was designed to examine the effectiveness and safety of dupilumab in moderate-to-severe AD in a real-world setting in Germany. Here, we present 12-week effectiveness and safety results with dupilumab from PROLEAD. Methods PROLEAD is a multicentre, prospective, non-interventional study being conducted at 126 routine care sites across Germany. Adults with moderate-to-severe AD who require systemic therapy were treated with dupilumab as indicated by the Summary of Product Characteristics. Data collected included physician assessments (EASI, BSA, SCORAD, and IGA) and patient-reported outcomes (PROs [POEM, DLQI, EQ-5D-5L, Peak Pruritus NRS and MOS Sleep Scale]). Results Of 839 patients assessed for eligibility, 828 were included. The full analysis and safety analysis sets comprised 775 and 818 patients, respectively. The number of patients receiving concomitant therapy decreased from baseline to Week 12. Mean (standard deviation [SD]) percentage change in EASI score from baseline to Week 12 was –67.5% (48.4%) and was comparable across the four body regions. The proportion of patients achieving EASI-75 was 59.4% at Week 12. Mean (SD) Peak Pruritus NRS decreased from 7.4 (2.3) at baseline to 3.4 (2.6) at Week 12. Improvements from baseline to Week 12 were reported in all PROs assessed. No new safety signals were observed. Discussion Improvements in efficacy outcomes and adverse event rates in a real-world setting were more favourable than in phase 3 clinical trials. Conclusions The 12-week findings of PROLEAD demonstrate that treatment with dupilumab is effective and well tolerated, with rapid onset of action in signs, symptoms and QoL in patients with moderate-to-severe AD in the real world. Trial Registration Number DUPILL08907; NIS-Nr. 433.

Background: Transphyseal humeral separations (TPHS) are rare injuries often associated with non-accidental trauma, necessitating accurate diagnosis. This study aims to assess the accuracy of diagnosis of TPHS. Methods: A retrospective review was conducted at five academic pediatric institutions to identify all surgically treated TPHS in patients up to 4 years of age over a 25-year period. Demographics, misdiagnosis rates, and reported misdiagnoses were noted. Comparative analyses were performed to analyze the effects of patient age and injury mechanism on misdiagnosis rates. Results: Seventy-nine patients (average age: 17.4 months) were identified, with injury mechanisms including accidental trauma (n = 49), non-accidental trauma (n = 21), Cesarean-section (n = 6), and vaginal delivery (n = 3). Neither age nor injury mechanism were significantly associated with diagnostic accuracy in the emergency department (ED)/consulting physician group. ED/consulting physicians achieved an accurate diagnosis 46.7% of the time, while radiologists achieved an accurate diagnosis 26.7% of the time. Diagnostic accuracy did not correlate with Child Protective Services (CPS) involvement or with a delay in surgery of more than 24 h. However, a significant correlation (p = 0.03) was observed between injury mechanism and misdiagnosis rates. Conclusion: This multicenter analysis is the largest study assessing TPHS misdiagnosis rates, highlighting the need for raising awareness and considering advanced imaging or orthopedic consultation for accurate diagnosis. This also reminds orthopedic surgeons to always have vigilant assessment in treating pediatric elbow injuries. Level of Evidence: Level III–Retrospective Cohort Study.

Self-assessment of general health status has a significant influence on patient-related outcomes. The aims of this study were to investigate and compare the level of agreement between patients’ and dermatologists’ assessments of the severity of chronic hand eczema. From the German registry “German Chronic Hand Eczema Patient Long-Term Management Registry” (CARPE), 1,281 pairs of patients with chronic hand eczema and their dermatologists were included. Of these, 788 pairs served as a comparison 2 years after baseline. Concordance analyses found that complete concordance between patients’ and dermatologists’ assessments were 16.62% at baseline and 11.47% at follow-up. Overall, patients assessed their chronic eczema at baseline as more severe than did the dermatologists; whereas, at follow-up, patients assessed their condition as less severe than the dermatologists’ assessment. Bangdiwala’s B showed lower values of concordance for womens’ and older patients’ self-assessment with the dermatologists’ assessments. In conclusion, dermatologists should consider the patient’s perspective and the individual’s assessment of their chronic hand eczema in order to provide effective care in clinical practice.

Context: The treatment of allergic reactions to red tattoo dye is challenging in most cases, as local therapy often does not offer long-term improvement and laser therapy is considered relatively contraindicated by many authors owing to the risk of generalized side effects. Therefore, surgical removal of these tattoos is favored; shave excision is the method of choice, particularly for the removal of the entire dye. Aims: The aim of this article was to retrospectively analyze the best post-operative outcome after surgical removal of allergic tattoo reactions using different excision techniques. Materials and Methods: We compared the different surgical procedures performed on seven patients with single and multiple allergic tattoo reactions treated between 2013 and 2018. Results: The best aesthetic results were achieved by superficial ablation of the inflammatory reaction, partially leaving tattoo remains in the skin. Conclusion: Based on our experience with this small number of patients, a superficial removal of the tattoo without complete removal of the dye is, in most cases, sufficient to achieve healing. The remaining dye residues seem to be better tolerated by the immune system afterwards. Furthermore, the tattoo is often preserved in large parts.

Introduction: Granuloma annulare (GA) has been reported as associated with multiple diseases, mainly diabetes mellitus (DM), thyroid diseases, and dyslipidemia. However, the high prevalence of some of these illnesses makes it difficult to assess whether the association is real or fortuitous. Our objective was to analyse the clinical features of our GA patients and the possible associations. Methods: This is a retrospective observational study of 225 patients with biopsy-proven GA diagnosed between 2009 and 2019 in a referral university hospital in Barcelona, Spain. Clinical charts were reviewed to obtain clinical data. As a control group we used a random list of 225 patients diagnosed in the hospital's traumatology department in the same period, matched by age and sex. Results: Diabetes was diagnosed in 40 GA patients (18%) (34 in the control group, 15%) and hypothyroidism in 33 (15%) (22 in the control group 9.8%); the differences were not significant. We also did not detect any association with uveitis, sarcoidosis, necrobiosis lipoidica, Sweet's syndrome, HIV infection, hepatitis B, or haematological malignancies. We only detected a possible association with hepatitis C (6 GA patients, 2.7%, versus 0 controls, p = 0.03), and hypercholesterolemia (108 GA patients, 48%, versus 79 controls, 35%, p = 0.007). Conclusions: The possible pathogenic explanations for the association with hepatitis C and hypercholesterolemia seem unlikely. We consider that the association of GA with other diseases, including hypercholesterolemia and hepatitis C, is doubtful and that it there is no justification rule out possible associated diseases in patients with GA.

Despite Xinomavro (Vitis vinifera L.) being a well-known noble red grape variety of northern Greece, little is known about its ‘‘bouquet’’ typicity. Volatile compounds of Xinomavro wines produced using a common vinification protocol were analyzed by gas chromatography–mass spectrometry and sensory descriptive analysis was carried out with a trained panel. Wines were characterized by the presence of fatty acids, ethyl and acetate esters, and alcohols, with contributions from terpenes and a volatile phenol. The most active aroma compounds were determined to be 3-methylbutyl acetate, β-damascenone, ethyl esters of octanoic and hexanoic acids, and eugenol. Those compounds positively correlated with fruity and spicy odor descriptors, with the wines being mostly characterized by five typical aroma terms: strawberry, berry fruit, spices, tomato, and green bell pepper. Partial least squares regression (PLSR) analysis was used to visualize relationship between the orthonasal sensory attributes and the volatile aroma compounds with calculated OAVs > 1. Key aroma-active volatiles in the wines were identified using GC-MS/olfactometry, providing a list of 40 compounds, among which 13 presented a modified detection frequency > 70%. This study is the first of its kind and provided strong indications regarding the aroma compounds defining the sensory characteristics of Xinomavro wines.

Rosai-Dorfman-Destombes disease (RDD) or sinus histiocytosis with massive lymphadenopathy is a rare non-Langerhans cell histiocytosis of unknown cause. The disease often manifests as bilateral painless cervical lymphadenopathy associated with systemic symptoms such as fever and weight loss. Extranodal disease is also frequent and can involve any organ, mostly skin, nasal cavity, bone, and retro-orbital tissue. Swelling of cartilaginous tissues such as ear helix or laryngeal structures may mimic the entity known as relapsing polychondritis. Although spontaneous remission is the most expected evolution, some cases require systemic treatment with prednisone, methotrexate or cytotoxic agents, with variable success rates. In this respect, since somatic variants in genes involved in the mitogen-activated protein kinase (MAPK) pathway have been observed to play a pathogenic role in RDD, the use of therapies targeting these pathogenic variants seems to be a reasonable strategy. Here we present a case of RDD with extensive extranodal involvement that showed a rapid and complete response to the MEK inhibitor cobimetinib

Abstract Introduction Personalized therapy for patients with COPD requires appropriate choice of drug and delivery device. Inhalers and nebulizers vary in their drug delivery characteristics, particularly the need for passive or active patient inhalation for appropriate drug dispersal and delivery. In this in vitro analysis, we assessed the aerosol performance and drug delivery of two long-acting muscarinic antagonists, glycopyrrolate (GLY; 25 µg solution; 1 ml) and tiotropium (TIO; 18 µg powder) through their respective delivery systems: the eFlow® Closed System (CS) vibrating membrane nebulizer and the HandiHaler® dry-powder inhaler (DPI). Methods The aerosol performances of the eFlow® CS nebulizer and the HandiHaler® were determined using the Next Generation cascade Impactor. The delivered dose of GLY and TIO was determined using different breathing patterns, which varied in tidal volume and peak inspiratory flow rate, respectively, to simulate breathing conditions ranging from normal to severe obstruction. Results Aerodynamic particle analysis showed generally similar mass median aerodynamic diameter (MMAD, range, 3.6–4.6 µm) and fine particle fraction (FPF, range, 48.2%–63.7%) with GLY delivered using the eFlow® CS nebulizer under all breathing patterns tested. TIO, delivered via the HandiHaler®, showed variations in MMAD (range, 3.8–5.8 µm) and FPF (range, 16.1%–32.4%) under different inspiratory flow rates. The majority of GLY was deposited in stages 2–5 of the impactor, which corresponds with particle sizes in the respirable range (

Abstract Background Information/communication technologies such as mobile phone applications (apps) would enable chronic urticaria (CU) patients to self‐evaluate their disease activity and control. Yet, recently Antó et al (2021) reported a global paucity of such apps for patients with CU. In this analysis, we assessed patient interest in using apps to monitor CU disease activity and control using questions from the chronic urticaria information and communication technologies (CURICT) study. Methods The methodology for CURICT has been reported. Briefly, a 23‐item questionnaire was completed by 1841 CU patients from 17 UCAREs across 17 countries. Here, we analyzed patient responses to the CURICT questions on the use of apps for urticaria‐related purposes. Results As previously published, the majority of respondents had chronic spontaneous urticaria (CSU; 63%; 18% chronic inducible urticaria (CIndU) [CIndu]; 19% with both), were female (70%) and in urban areas (75%). Over half of patients were very/extremely interested in an app to monitor disease activity (51%) and control (53%), while only ∼1/10 were not. Patients with both urticaria types versus those with CSU only (odds ratio [OR], 1.36 [1.03–1.79]) and females versus males (OR [95% CI], 1.47 [1.17–1.85]) were more likely to be very to extremely interested in an app to assess disease control. Conclusions Overall, half of the patients with CU were very to extremely interested in using an app to assess their disease activity and control. Development of well‐designed apps, specific to disease types (CSU, CIndU, CSU + CIndU, etc), validated by experts across platforms would help improve the management and possibly outcomes of CU treatment while providing important patient information to be used in future research.

Background: Patients with chronic urticaria (CU) are increasingly using information and communication technologies (ICTs) to manage their health. What CU patients expect from ICTs and which ICTs they prefer remains unknown. We assessed why CU patients use ICTs, which ones they prefer, and what drives their expectations and choices. Methods: In this cross-sectional study, 1841 patients across 17 countries were recruited at UCAREs (Urticaria Centers of Reference and Excellence). Patients with CU who were >12 years old completed a 23-item questionnaire. Results: Most patients were interested in receiving disease information (87.3%), asking physicians about CU (84.1%), and communicating with other patients through ICTs (65.6%). For receiving disease information, patients preferred one-to-one and one-to-many ICTs, especially web browsers. One-to-one ICTs were also the ICTs of choice for asking physicians about urticaria and for communicating with other patients, and e-mail and WhatsApp were the preferred ICTs, respectively. Many-to-many ICTs such as Facebook, Instagram, LinkedIn, and Twitter were least preferred for all 3 purposes. Living in rural areas and higher education were linked to higher odds of being interested in receiving disease information, asking physicians, and communicating with patients through ICTs. Conclusions: Most patients and especially patients with higher education who live in rural areas are interested in using ICTs for their healthcare, but prefer different ICTs for different purposes, ie, web browsers for obtaining information, e-mail for asking physicians, and WhatsApp for communicating with other patients. Our findings may help to improve ICTs for CU.

Background: Chronic urticaria (CU) is characterized by itchy recurrent wheals, angioedema, or both for 6 weeks or longer. CU can greatly impact patients' physical and emotional quality of life. Patients with chronic conditions are increasingly seeking information from information and communications technologies (ICTs) to manage their health. The objective of this study was to assess the frequency of usage and preference of ICTs from the perspective of patients with CU. Methods: In this cross-sectional study, 1800 patients were recruited from primary healthcare centers, university hospitals or specialized clinics that form part of the UCARE (Urticaria Centers of Reference and Excellence) network throughout 16 countries. Patients were >12 years old and had physician-diagnosed chronic spontaneous urticaria (CSU) or chronic inducible urticaria (CIndU). Patients completed a 23-item questionnaire containing questions about ICT usage, including the type, frequency, preference, and quality, answers to which were recorded in a standardized database at each center. For analysis, ICTs were categorized into 3 groups as follows: one-to-one: SMS, WhatsApp, Skype, and email; one-to-many: YouTube, web browsers, and blogs or forums; many-to-many: Instagram, Twitter, Facebook, and LinkedIn. Results: Overall, 99.6% of CU patients had access to ICT platforms and 96.7% had internet access. Daily, 85.4% patients used one-to-one ICT platforms most often, followed by one-to-many ICTs (75.5%) and many-to-many ICTs (59.2%). The daily ICT usage was highest for web browsers (72.7%) and WhatsApp (70.0%). The general usage of ICT platforms increased in patients with higher levels of education. One-to-many was the preferred ICT category for obtaining general health information (78.3%) and for CU-related information (75.4%). A web browser (77.6%) was by far the most commonly used ICT to obtain general health information, followed by YouTube (25.8%) and Facebook (16.3%). Similarly, for CU-specific information, 3 out of 4 patients (74.6%) used a web browser, 20.9% used YouTube, and 13.6% used Facebook. One in 5 (21.6%) patients did not use any form of ICT for obtaining information on CU. The quality of the information obtained from one-to-many ICTs was rated much more often as very interesting and of good quality for general health information (53.5%) and CU-related information (51.5%) as compared to the other categories. Conclusions: Usage of ICTs for health and CU-specific information is extremely high in all countries analyzed, with web browsers being the preferred ICT platform.

Abstract Using Chlamydia trachomatis (Ct) as a complex model organism, we describe a method to generate bacterial whole-proteome microarrays using cell-free, on-chip protein expression. Expression constructs were generated by two successive PCRs directly from bacterial genomic DNA. Bacterial proteins expressed on microarrays display antigenic epitopes, thereby providing an efficient method for immunoprofiling of patients and allowing de novo identification of disease-related serum antibodies. Through comparison of antibody reactivity patterns, we newly identified antigens recognized by known Ct-seropositive samples, and antigens reacting only with samples from cervical cancer (CxCa) patients. Large-scale validation experiments using high-throughput suspension bead array serology confirmed their significance as markers for either general Ct infection or CxCa, supporting an association of Ct infection with CxCa. In conclusion, we introduce a method for generation of fast and efficient proteome immunoassays which can be easily adapted for other microorganisms in all areas of infection research.

Until recently, whole-proteome microarrays for comprehensive studies of protein interactions were mostly produced by individual cloning and cellular expression of very many open reading frames, followed by protein isolation and purification as well as array production. To overcome this cumbersome process, we have developed a method to generate microarrays representing entire proteomes by a combination of multiple spotting and on-chip, cell-free protein expression. Here, we describe the protocol for the production of bacterial protein microarrays. With slight adaptations, however, the procedure can be applied to the proteome of any organism. Expression constructs of each gene are generated by PCR on bacterial genomic DNA followed by a common secondary amplification that is adding relevant regulative elements to either end of the constructs. The unpurified PCR-products are spotted onto the microarray surface. Full-length proteins are directly expressed in situ in a cell-free manner and stay attached to the surface without further action. As an example of a typical application, we describe here the proteome-wide analysis of the immune response to a bacterial infectious agent by characterizing the binding profiles of the antibodies in patient sera.

Identification of disease-associated autoantibodies is of high importance. Their assessment could complement current diagnostic modalities and assist the clinical management of patients. We aimed at developing and validating high-throughput protein microarrays able to screen patients’ sera to determine disease-specific autoantibody-signatures for pancreatic cancer (PDAC), chronic pancreatitis (CP), autoimmune pancreatitis and their subtypes (AIP-1 and AIP-2). In-house manufactured microarrays were used for autoantibody-profiling of IgG-enriched preoperative sera from PDAC-, CP-, AIP-1-, AIP-2-, other gastrointestinal disease (GID) patients and healthy controls. As a top-down strategy, three different fluorescence detection-based protein-microarrays were used: large with 6400, intermediate with 345, and small with 36 full-length human recombinant proteins. Large-scale analysis revealed 89 PDAC, 98 CP and 104 AIP immunogenic antigens. Narrowing the selection to 29 autoantigens using pooled sera first and individual sera afterwards allowed a discrimination of CP and AIP from PDAC. For validation, predictive models based on the identified antigens were generated which enabled discrimination between PDAC and AIP-1 or AIP-2 yielded high AUC values of 0.940 and 0.925, respectively. A new repertoire of autoantigens was identified and their assembly as a multiplex test will provide a fast and cost-effective tool for differential diagnosis of pancreatic diseases with high clinical relevance.

Proteins are the major class of effector molecules in cellular systems. For the identification of functional differences between normal and diseased tissues, a reliable analysis of their protein content is essential. Reproducible isolation and fractionation of intact proteins are important in this respect, but their complexity in structure and concentration, their close interaction, and their instability represent major challenges. For protein isolation in tissues, the breakdown of cell-cell and cell-matrix connections within a tissue without affecting protein quality is a critical factor. We compared different processes for a compartmental protein preparation from pancreatic tissue, one of the most challenging tissues for protein isolation because of its high protease content. Success of the different procedures varied greatly. Based on a scheme of tissue-slicing and subsequent cell isolation, we established a reliable workflow for the fractional extraction of cytosolic proteins, membrane and organelle proteins, nuclear proteins, and cytoskeletal filaments. The tissue slices also allow for a representative confirmation of individual samples' cellular status by histochemical processes, and a proper separation or mixing of cellular material from across a tumor if required.

Pancreatic cancer has one of the worst mortality rates of all cancers. Little is known about its etiology, particularly regarding inherited risk. The PanScan project, a genome-wide association study, identified several common polymorphisms affecting pancreatic cancer susceptibility. Single nucleotide polymorphisms (SNPs) in ABO, sonic hedgehog (SHH), telomerase reverse transcriptase (TERT), nuclear receptor subfamily 5, group A, member 2 (NR5A2) were found to be associated with pancreatic cancer risk. Moreover the scan identified loci on chromosomes 13q22.1 and 15q14, to which no known genes or other functional elements are mapped. We sought to replicate these observations in two additional, independent populations (from Germany and the UK), and also evaluate the possible impact of these SNPs on patient survival. We genotyped 15 SNPs in 690 cases of pancreatic ductal adenocarcinoma (PDAC) and in 1277 healthy controls. We replicated several associations between SNPs and PDAC risk. Furthermore we found that SNP rs8028529 was weakly associated with a better overall survival (OS) in both populations. We have also found that NR5A2 rs12029406_T allele was associated with a shorter survival in the German population. In conclusion, we found that rs8028529 could be, if these results are replicated, a promising marker for both risk and prognosis for this lethal disease.