Dye-Perfused Human Placenta for Simulation in a Microsurgery Laboratory for Plastic Surgeons.

In recent decades, a number of simulation models for microsurgical training have been published. The human placenta has received extensive validation in microneurosurgery and is a useful instrument to facilitate learning in microvascular repair techniques as an alternative to using live animals. This study uses a straightforward, step-by-step procedure for instructing the creation of simulators with dynamic flow to characterize the placental vascular tree and assess its relevance for plastic surgery departments. Measurements of the placental vasculature and morphological characterization of 18 placentas were made. After the model was used in a basic microsurgery training laboratory session, a survey was given to nine plastic surgery residents, two microsurgeons, and one hand surgeon. In all divisions, venous diameters were larger than arterial diameters, with minimum diameters of 0.8 and 0.6 mm, respectively. The majority of the participants considered that the model faithfully reproduces a real microsurgical scenario; the consistency of the vessels and their dissection are similar in in vivo tissue. Furthermore, all the participants considered that this model could improve their surgical technique and would propose it for microsurgical training. As some of the model's disadvantages, an abundantly thick adventitia, a thin tunica media, and higher adherence to the underlying tissue were identified. The color-perfused placenta is an excellent tool for microsurgical training in plastic surgery. It can faithfully reproduce a microsurgical scenario, offering an abundance of vasculature with varying sizes similar to tissue in vivo, enhancing technical proficiency, and lowering patient error.

Regulatory T cells in allergic inflammation.

Regulatory T (Treg) cells maintain immune tolerance to allergens at the environmental interfaces in the airways, skin and gut, marshalling in the process distinct immune regulatory circuits operative in the respective tissues. Treg cells are coordinately mobilized with allergic effector mechanisms in the context of a tissue-protective allergic inflammatory response against parasites, toxins and potentially harmful allergens, serving to both limit the inflammation and promote local tissue repair. Allergic diseases are associated with subverted Treg cell responses whereby a chronic allergic inflammatory environment can skew Treg cells toward pathogenic phenotypes that both perpetuate and aggravate disease. Interruption of Treg cell subversion in chronic allergic inflammatory conditions may thus provide novel therapeutic strategies by re-establishing effective immune regulation.

Bos d 13, A Novel Heat-Stable Beef Allergen.

SCOPE: Red meat, a staple food of Western diets, can also induce IgE-mediated allergic reactions. Yet, apart from the heat-labile protein serum albumin and the carbohydrate α-Gal, the molecules causing allergic reactions to red meat remain unknown. METHODS AND RESULTS: IgE reactivity profiles of beef-sensitized individuals are analyzed by IgE-immunoblotting with protein extracts from raw and cooked beef. Two IgE-reactive proteins are identified by peptide mass fingerprinting as myosinlight chain 1 (MYL1) and myosin light chain 3 (MYL3) in cooked beef extract and are designated Bos d 13 isoallergens. MYL1 and MYL3 are produced recombinantly in Escherichia coli. ELISAs proved their IgE reactivity and circular dichroism analysis showed that they represent folded molecules with remarkable thermal stability. In vitro gastrointestinal digestion experiments showed the higher stability of rMYL1 as compared to rMYL3. Exposure of a monolayer of Caco-2 cells to rMYL1 indicated that the molecule is able to cross intestinal epithelial cells without disturbing the integrity of the tight junctions, suggesting the sensitizing capacity of MYL1. CONCLUSION: MYLs are identified as novel heat-stable bovine meat allergens.

Severe allergic dysregulation due to a gain of function mutation in the transcription factor STAT6.

BACKGROUND: Inborn errors of immunity have been implicated in causing immune dysregulation, including allergic diseases. STAT6 is a key regulator of allergic responses. OBJECTIVES: This study sought to characterize a novel gain-of-function STAT6 mutation identified in a child with severe allergic manifestations. METHODS: Whole-exome and targeted gene sequencing, lymphocyte characterization, and molecular and functional analyses of mutated STAT6 were performed. RESULTS: This study reports a child with a missense mutation in the DNA binding domain of STAT6 (c.1114G>A, p.E372K) who presented with severe atopic dermatitis, eosinophilia, and elevated IgE. Naive lymphocytes from the affected patient displayed increased TH2- and suppressed TH1- and TH17-cell responses. The mutation augmented both basal and cytokine-induced STAT6 phosphorylation without affecting dephosphorylation kinetics. Treatment with the Janus kinase 1/2 inhibitor ruxolitinib reversed STAT6 hyperresponsiveness to IL-4, normalized TH1 and TH17 cells, suppressed the eosinophilia, and improved the patient's atopic dermatitis. CONCLUSIONS: This study identified a novel inborn error of immunity due to a STAT6 gain-of-function mutation that gave rise to severe allergic dysregulation. Janus kinase inhibitor therapy could represent an effective targeted treatment for this disorder.

Vacuum-Assisted Block Freeze Concentration Studies in Cheese Whey and Its Potential in Lactose Recovery.

Block freeze concentration (BFC) is considered an emerging technology which allows the acquiring of high quality organoleptic products, due to the low temperatures employed. In this study we have outlined how the vacuum-assisted BFC of whey was investigated. The effects of vacuum time, vacuum pressure, and the initial solids concentration in whey were studied. The results obtained show that the three variables significantly affect each of the following parameters analysed: solute yield (Y) and concentration index (CI). The best Y results were obtained at a pressure of 10 kPa, 7.5 °Bx, and 60 min. For CI parameter, the highest values were given at 10 kPa, 7.5 °Bx, and 20 min, respectively. In a second phase, by applying the conditions that provide higher solute yield to three different types of dairy whey, Y values of 70% or higher are reached in a single step, while that the CI of lactose are higher than those of soluble solids. Therefore, it is possible to recover, in a single step, at least 70% of the lactose contained in the initial whey samples. This suggests that vacuum-assisted BFC technology may be an interesting alternative for the recovery of lactose contained in whey.

Anatomical and histomorphometric study of the ulnar nerve at the wrist / Estudio anatómico e histomorfométrico del nervio ulnar en la muñeca

SUMMARY: The ulnar nerve (UN) is the main nerve responsible for innervation of the intrinsic musculature of the hand. It is of great importance to have a deep anatomical knowledge of the UN. The aim of this study is to enrich the knowledge of the UN anatomy at the wrist and provide useful reference information for clinical and surgical applications. In this descriptive cross-sectional study, 44 upper limbs of fresh cadavers were evaluated. The UN, the superficial branch of the ulnar nerve (SBUN), and the deep branch of the ulnar nerve (DBUN) were evaluated. Morphometric variables were measured using a digital caliper, and samples of nervous tissue were taken to evaluate the histomorphometry. Before entering the Guyon's canal, the UN had a diameter of 3.2 ± 0.4 mm. In 36 samples (82 %) the UN presented a bifurcation pattern and in the remaining 8 samples (18 %) a trifurcation was shown. The diameter of the DBUN was 1.9 ± 0.33 mm and that of the SBUN was 1.29 ± 0.22 mm. In the bifurcation patterns, the SBUN had a trunk of 5.71 ± 1.53 mm before bifurcating into the common digital nerve (fourth and fifth fingers) and an ulnar digital collateral nerve (fifth finger). The DBUN had an area of 2.84 ± 0.7 mm2 and was made up of 8 ± 1.4 fascicles and 3595 ± 465 axons. The SBUN area was 1.31 ± 0.27 mm2, it was made up of 6 ± 1.1 fascicles and 2856 ± 362 axons. The reported findings allow the hand surgeon to improve his understanding of the clinical signs of patients with UN pathologies at the wrist level and thus achieve greater precision while planning and performing surgical approaches and dissections.

El nervio ulnar (NU) es el principal nervio responsable de la inervación de la musculatura intrínseca de la mano. Es de gran importancia tener un profundo conocimiento anatómico del NU. El objetivo de este estudio fue enriquecer el conocimiento de la anatomía del NU en la muñeca y proporcionar información de referencia útil para aplicaciones clínicas y quirúrgicas. En este estudio descriptivo transversal se evaluaron 44 miembros superiores de cadáveres frescos. Se evaluó el NU, el ramo superficial del nervio ulnar (RSNU) y el ramo profundo del nervio ulnar (RPNU). Las variables morfométricas se midieron con un caliper digital y se tomaron muestras del nervio para evaluar la histomorfometría. Antes de ingresar al canal del nervio ulnar (canal Guyon), el ONU tenía un diámetro de 3,2 ± 0,4 mm. En 36 muestras (82 %) el ONU presentó un patrón de bifurcación y en las 8 muestras restantes (18 %) se presentó una trifurcación. El diámetro del RPNU fue de 1,9 ± 0,33 mm y el del RSNU de 1,29 ± 0,22 mm. En los patrones de bifurcación, el RSNU presentó un tronco de 5,71 ± 1,53 mm antes de bifurcarse en el nervio digital común (cuarto y quinto dedo) y un nervio digital colateral ulnar (quinto dedo). El RPNU tenía un área de 2,84 ± 0,7 mm2 y estaba formado por 8 ± 1,4 fascículos y 3595 ± 465 axones. El área del RSNU fue de 1,31 ± 0,27 mm2, estaba formado por 6 ± 1,1 fascículos y 2856 ± 362 axones. Los hallazgos reportados permiten al cirujano de mano mejorar su comprensión de los signos clínicos de los pacientes con patologías del NU a nivel de la muñeca y así lograr una mayor precisión en la planificación y realización de abordajes y disecciones quirúrgicas.

The posterior interosseous nerve at the proximal forearm: anatomical study and clinical correlation / El nervio interóseo posterior en el antebrazo proximal: estudio anatómico y correlación clínica

SUMMARY: The deep branch of the radial nerve (DBRN) runs through the radial tunnel, which is a muscle-aponeurotic structure that extends from the humeral lateral epicondyle to the distal margin of the supinator muscle (SM). The Posterior Interosseous Nerve (PIN) originates as a direct continuation of the DBRN as it emerges from the SM and supplies most of the muscles of the posterior compartment of the forearm. The PIN can be affected by compressive neuropathies, especially at the "Arcade of Frohse". Its preservation is of special interest in surgical approaches to proximal radius fractures and in compressive syndromes release, for which surgeons must have an adequate anatomical knowledge of its course. This descriptive cross-sectional study evaluated 40 upper limbs of fresh cadavers. The diameters of the DBRN, the length of the radial tunnel, and the distances to the supinator arch, PIN emergence and PIN bifurcation were measured. The deep branch of the radial nerve (DBRN) has a course of 23.8 ± 3.7 mm from its origin to the supinator arch, presenting a diameter of 2.2 ± 0.3 mm at that level. The length of the radial tunnel was 42.2 ± 4 mm. The PIN originated 70.7 ± 3.5 mm distal to the lateral epicondyle. Type I corresponds to the division of the PIN during its journey through the radial tunnel, presenting in 35 % of cases, and Type II corresponds to the division of the PIN distal to its emergence from the radial tunnel presenting in the remaining 65 %. This study enriches the knowledge of the PIN and provides useful reference information on a Latin American mestizo sample. We propose the division pattern of the PIN into two types. Future studies may use this classification not only as a qualitative variable, but also include quantitative morphometric measurements.

El ramo profundo del nervio radial (RPNR) discurre por el túnel radial, que es una estructura músculo- aponeurótica que se extiende desde el epicóndilo lateral del húmero humeral hasta el margen distal del músculo supinador (MS). El nervio interóseo Posterior (NIP) se origina como una continuación directa del RPNR cuando emerge del MS e inerva la mayoría de los músculos del compartimiento posterior del antebrazo. El NIP puede verse afectado por neuropatías compresivas, especialmente en la "Arcada de Frohse". Su conservación es de especial interés en los abordajes quirúrgicos de las fracturas proximales de radio y en la liberación de síndromes compresivos, para lo cual los cirujanos deben tener un adecuado conocimiento anatómico de su curso. Este estudio descriptivo transversal evaluó 40 miembros superiores de cadáveres frescos. Se midieron los diámetros de la RPNR, la longitud del túnel radial y las distancias al arco supinador, la emergencia del NIP y la bifurcación del NIP. El RPNR tenía un recorrido de 23,8 ± 3,7 mm desde su origen hasta el arco supinador, presentando un diámetro de 2,2 ± 0,3 mm a ese nivel. La longitud del túnel radial fue de 42,2 ± 4 mm. El NIP se originó 70,7 ± 3,5 mm distal al epicóndilo lateral. El tipo I corresponde a la división del NIP durante su recorrido por el túnel radial presentándose en el 35 % de los casos, y el tipo II corresponde a la división del NIP distal a su salida del túnel radial presentándose en el 65 % restante. Este estudio enriquece el conocimiento del NIP y proporciona información de referencia útil sobre una muestra de mestizos latinoamericanos. Proponemos el patrón de división del NIP en dos tipos. Futuros estudios pueden utilizar esta clasificación no solo como una variable cualitativa, sino también incluir medidas morfométricas cuantitativas.

Critical features of an in vitro intestinal absorption model to study the first key aspects underlying food allergen sensitization.

New types of protein sources will enter our diet in a near future, reinforcing the need for a straightforward in vitro (cell-based) screening model to test and predict the safety of these novel proteins, in particular their potential risk for de novo allergic sensitization. The Adverse Outcome Pathway (AOP) for allergen sensitization describes the current knowledge of key events underlying the complex cellular interactions that proceed allergic food sensitization. Currently, there is no consensus on the in vitro model to study the intestinal translocation of proteins as well as the epithelial activation, which comprise the first molecular initiation events (ME1-3) and the first key event of the AOP, respectively. As members of INFOGEST, we have highlighted several critical features that should be considered for any proposed in vitro model to study epithelial protein transport in the context of allergic sensitization. In addition, we defined which intestinal cell types are indispensable in a consensus model of the first steps of the AOP, and which cell types are optional or desired when there is the possibility to create a more complex cell model. A model of these first key aspects of the AOP can be used to study the gut epithelial translocation behavior of known hypo- and hyperallergens, juxtaposed to the transport behavior of novel proteins as a first screen for risk management of dietary proteins. Indeed, this disquisition forms a basis for the development of a future consensus model of the allergic sensitization cascade, comprising also the other key events (KE2-5).

¿Diagnóstico o estigma? Problematizar la enfermedad desde un acercamiento duoetnográfico

Objetivo: El propósito de este escrito es hablar sobre las construcciones socioculturales alrededor de la enfermedad. La principal preocupación es contribuir a desmontar desde nuestras vivencias como investigadoras y mujeres diagnosticadas, el estigma que impregna la vida cotidiana de las personas como nosotras: obesas o con VPH (virus del papiloma humano). Metodología: Mediante la metodología conocida como duoetnografía, en la que dos individuos narran experiencias compartidas para profundizar sobre un fenómeno sociocultural, presentamos una serie de cavilaciones que cuestionan el lugar social en el que se nos coloca al ser valuadas como enfermas. Resultados: Encontramos, a partir de nuestras reflexiones simultáneas, tres epifanías que se relacionan, primero, con el estigma biomédico, luego, con el estigma personal y, después, con el estigma sociocultural. Una cuarta epifanía expone las consideraciones de aprendizaje conjunto durante el proceso de convivencia académica de las autoras. Conclusión: Nos interesa, sobre todo, dejar una invitación a considerar críticamente el estigma, nos preocupa hablar de cuidado y apuntar las prácticas discriminatorias más que negar nuestros diagnósticos.

Objetivo: O objetivo deste trabalho é falar sobre as construções socioculturais que envolvem a doença. A principal preocupação é contribuir para desmontar, desde nossas experiências como pesquisadores e mulheres diagnosticadas, o estigma que permeia a vida diária de pessoas como nós: obesas ou com HPV (Human Papilloma Virus). Metodologia: Por meio da metodologia conhecida como duoetnografia, na qual dois indivíduos narram experiências compartilhadas a fim de aprofundar um fenômeno sociocultural, apresentamos uma série de reflexões que questionam o lugar social em que somos colocados quando somos categorizadas como doentes. Resultados: Encontramos, a partir de nossas reflexões simultâneas, três epifanias que se relacionam primeiro com o estigma biomédico, depois com o estigma pessoal e depois com o estigma sociocultural. Uma quarta epifania expõe as considerações de aprendizagem conjunta durante o processo de convivência acadêmica das autoras. Conclusão: Estamos interessados, acima de tudo, em deixar um convite para considerar criticamente o estigma, estamos preocupadas em falar de cuidados e apontar práticas discriminatórias em vez de negar nossos diagnósticos.

Objective: The purpose of this paper is to talk about the sociocultural constructions around the disease. The main interest is to contribute to dismantle from our experiences as researchers and diagnosed women, the stigma that permeates the daily lives of people like us: obese or with HPV (Human Papilloma Virus). Methodology: Through the methodology known as duoethnography, in which two individuals narrate shared experiences to study in detail a sociocultural phenomenon, we present a series of thoughts that question the place in which we are placed when we are valuated as sick. Results: We found, from our simultaneous reflections, three epiphanies that relate first to biomedical stigma, then to personal stigma and then to sociocultural stigma. A fourth epiphany expounds joint learning considerations during the authors' academic shared experience. Conclusion: We are interested, above all, in leaving an invitation to critically consider stigma, we are concerned with talking about care and pointing out discriminatory practices rather than denying our diagnoses.

IgE-Binding and Immunostimulating Properties of Enzymatic Crosslinked Milk Proteins as Influenced by Food Matrix and Digestibility.

Dairy foods are essential in the diet, although in some susceptible individuals they may cause allergy to cow's milk proteins. Therefore, alternative methods are sought to reduce their allergenicity. Transglutaminase (TG) is widely used in dairy products mainly to improve texture. Although it has been claimed that TG can be used to modify the digestibility and allergenicity of foods, its impact within a real matrix has been rarely studied. The aim of this work was to assess the allergenic potential of crosslinked skim milk (SM), milk casein fraction (CN), and whey protein (WP). To this purpose, inhibition ELISA with sera from milk allergic patients, in vitro activation tests of mouse mast cells and splenocytes, and simulated gastrointestinal digestion assays were performed. The results showed that cross-linking increased the binding of IgE to WP, but decreased IgE-binding to SM and CN. However, no differences were observed in the ability of cross-linked proteins to induce mast cell degranulation compared to native proteins. The cross-linking of SM and CN reduced Th2 cytokine release from the splenocytes of sensitized mice. All TG-treated samples exhibited more resistance to in vitro digestion than the untreated proteins and the human IgE binding capacity after digestion was higher. In conclusion, TG treatment of milk proteins does not reduce the risk of eliciting allergic symptoms in cow's milk allergic patients.

An Agrobacterium strain auxotrophic for methionine is useful for switchgrass transformation.

Auxotrophic strains of Agrobacterium tumefaciens can contribute to the development of more efficient transformation systems, especially for crops historically considered recalcitrant. Homologous recombination was used to derive methionine auxotrophs of two common A. tumefaciens strains, LBA4404 and EHA105. The EHA105 strains were more efficient for switchgrass transformation, while both the EHA105 and LBA4404 strains worked equally well for the rice control. Event quality, as measured by transgene copy number, was not affected by auxotrophy, but was higher for the LBA4404 strains than the EHA105 strains. Ultimately, the use of auxotrophs reduced bacterial overgrowth during co-cultivation and decreased the need for antibiotics.

Control of Listeria monocytogenes growth and virulence in a traditional soft cheese model system based on lactic acid bacteria and a whey protein hydrolysate with antimicrobial activity.

"Torta del Casar" is a Spanish soft-ripened cheese made with sheep's raw milk and subjected to a short ripening process, which favors the growth of pathogenic microorganisms including Listeria monocytogenes. The development of strategies to control pathogens and minimize health risks associated with the presence of L. monocytogenes in these products is of great interest. In this regard, the anti-Listeria activity of a whey protein hydrolysate (ProH) alone or combined with six lactic acid bacteria strains isolated from cheese was evaluated in this study as a biocontrol strategy using a "Torta del Casar" cheese-based medium. The most active combinations of lactic acid bacteria assayed induced a reduction higher than two logarithmic units in the growth of L. monocytogenes (serotype 4b) compared to their respective control when they were co-inoculated in "Torta del Casar" cheese-based medium at 7 °C for 7 days. In addition, the observed downregulation of some key virulence genes of L. monocytogenes suggests that the strain Lactiplantibacillus plantarum B2 alone and combined with the strain Lactiplantibacillus spp. B4 are good candidates to be used as biocontrol agents against L. monocytogenes growth in traditional soft cheeses based on raw milk during their storage at refrigeration temperatures.

Storage Proteins Are Driving Pediatric Hazelnut Allergy in a Lipid Transfer Protein-Rich Area.

Oral food challenge (OFC) remains the gold standard for the diagnosis of food allergies. However, this test is not without risks, given that severe allergic reactions can be triggered while it is conducted. The purpose of this study is to identify potential demographic variables, clinical characteristics of the patients and biomarkers that may be associated with severe reactions during the hazelnut oral challenge test. The sample included 22 children allergic to hazelnut who underwent a tree nut skin prick test (SPT), specific IgE (sIgE) to hazelnut, component-resolved diagnosis (CRD) with different hazelnut allergens (Cor a 1, Cor a 8, Cor a 9, Cor a 11, Cor a 14), and a single-blind placebo-controlled challenge with hazelnut. A statistically significant relationship was found between the severity of the reaction and the highest values of sIgE to hazelnut, Cor a 11 and Cor a 14, cumulative symptom-triggering dose and sunflower seed sensitization. The use of the CRD is a useful tool to identify patients at higher risk of developing a severe reaction. In this pediatric population sample from Spain, storage proteins were confirmed to be most involved in hazelnut allergy and the development of severe reactions.

Triacylglycerides and Phospholipids from Egg Yolk Differently Influence the Immunostimulating Properties of Egg White Proteins.

As part of a whole egg, egg white proteins are embedded in a lipid matrix that could modify their presentation to the immune system and their allergenic properties. The present study examines the impact of the main egg lipid components, triacylglycerides and phospholipids, in the early events of sensitization to egg. To this end, BALB/c mice were exposed intragastrically to egg lipids and egg lipid fractions, alone and in mixtures with egg white proteins, and Th2-promoting and proinflammatory effects were investigated. Our results highlight that the egg lipid fraction is responsible for Th2 adjuvant effects and point at a different influence of triacylglycerides and phospholipids on the bioavailability and immunomodulating properties of egg white proteins. While triacylglycerides promote type 2 responses at the small intestine level, phospholipids reduce the solubility of EW proteins and induce Th2 skewing in lymphoid intestinal tissues, which may have a direct impact on the development of egg allergy.

Retinoic Acid Induces Functionally Suppressive Foxp3+RORγt+ T Cells In Vitro.

Introduction: CD4+ T cells with regulatory function co-expressing Foxp3 and RORγt are linked to the development of oral tolerance towards innocuous food antigens in mice. This study aimed to discern the role played by IL-6 and retinoic acid (RA) in the in vitro generation of Foxp3+RORγt+ T cells and to investigate whether such cells have suppressive properties. Methods: CD4+CD25- T cells isolated from the spleen of BALB/c mice, were stimulated in the presence of IL-2 alone or together with TFG-ß and different concentrations of IL-6 and/or RA. Percentage of Foxp3+, RORγt+, IL-17+, Foxp3+RORγt-, Foxp3+RORγt+, and Foxp3-RORγt+ T cells within the total CD4+ T cell population, production of cytokines (IL-10 and IL-17A) and gene expression (Foxp3, Rorc, Tgfb1, Il6, Il10, and Il17) were assessed at different time points. The phenotype and ability of cells generated from CD4+CD44-CD62L+ cells in the presence of RA to suppress effector T cell proliferation was assessed. Results: TGF-ß plus IL-6 induced the generation of Foxp3+ and double positive Foxp3+RORγt+ T cells to a higher extent than TGF-ß alone at the beginning of the incubation period, although expression of Foxp3 subsequently declined. RA, added to TGF-ß, increased Foxp3 and Rorc expression and Foxp3 and RORγt transcription and promoted the differentiation of Foxp3+RORγt- and Foxp3+RORγt+ cells that expressed and secreted IL-17. Foxp3+ T cells generated in vitro in presence of RA were functionally suppressive. Conclusions: Under the influence of IL-2 and TGF-ß, suppressive Foxp3+RORγt+ T cells that express and secrete IL-17 can be produced in vitro and RA further contributes to stabilize this phenotype.

Demanda de medicamentos sin receta: evaluación de la intervención farmacéutica / Demand for drugs without prescription: Evaluation of pharmaceutical intervention

Introducción: La modificación de los usos y actitudes de los demandantes de dispensación de medicamentos que precisan receta médica sin presentarla, es un campo donde el farmacéutico comunitario, desde su responsabilidad profesional, puede contribuir a obtener importantes resultados en la consecución de su uso correcto.Objetivo: Evaluar el resultado de la intervención del farmacéutico en la demanda de medicamentos (ibuprofeno y paracetamol) sin presentar receta médica en presentaciones que la requieren. Método: Diseño: estudio experimental transversal aleatorizado con intervención farmacéutica mediante educación sanitaria.Emplazamiento: nueve farmacias de Pontevedra y Ourense. Octubre-noviembre de 2019.Participantes: usuarios de la farmacia que solicitaban sin receta presentaciones de paracetamol o ibuprofeno que la requerían.Mediciones principales: número de solicitudes, problemas de salud y motivos, aceptación o no de una alternativa de medicamento sinreceta (MSR).Resultados:Se registraron 424 peticiones, 303 (71,5%) aceptaron la dispensación del MSR. Ibuprofeno 600 mg fue el principio activo más solicitado (73,3%) y la automedicación el principal motivo de petición sin receta (89,9%). Entre los problemas de salud referidos destacó el dolor de cabeza (22,9%). No se encontraron diferencias significativas entre el resultado de la intervención y el medicamento solicitado, el sexo, el motivo, ni el problema de salud que originó la solicitud. Sí entre edad de los pacientes, medicamento solicitado y resultado de la intervención. 30 (14,2%) pacientes fueron derivados al médico.Conclusiones:La actuación del farmacéutico en el cambio a un medicamento sin receta logró una alta aceptación por los pacientes, lo que contribuye a su uso adecuado.(AU)

Introduction: The change in the usage and the attitudes of the petitioners who ask for the dispensing of medications that require a medical prescription without deliver it, is a field in which the community pharmacist, from his or her professional responsibility, can contribute to obtain important outcomes in the achievement of their correct usage.Objective:This study pursues to evaluate the result of the pharmacist intervention on the demand for drugs (ibuprofen and paracetamol) without delivering a medical prescription in cases in which it is needed. Method: Design: It was carried out an experimental, cross-sectional and randomized study with pharmaceutical intervention through health education.Location: nine pharmacies from Pontevedra and Ourense. October –November 2019.Participants: pharmacy users that ask for paracetamol or ibuprofeno without having a medical prescription although it was needed. Main measurements: number of requests, health problems and causes, acceptance or not of an alternative, an over the counter (OTC) drug. Results: 424 requests were registered, 303 (71.5%) accepted the OTC dispensation. Ibuprofeno 600 mg was the most requested active ingredient (73.3%) and self-medication the main cause of request without a prescription (89.9%). Among the health problems referred, headache stood out (22.9%). There were not found significant differences between the outcome of the intervention and the requested medication, the sex, the reason, or the health problem that was the origin of the request. On the other hand, important differences were found in the age of the patients, the requested medication and the result of the intervention. 30 (14.2%) patients were referred to the doctor. Conclusions: The intervention of the pharmacist in the change to an over the counter drug achieved a high acceptance from the patients, which contributes to their correct usage.(AU)

Oral Exposure to House Dust Mite Activates Intestinal Innate Immunity.

SCOPE: House dust mite (HDM) induces Th2 responses in lungs and skin, but its effects in the intestine are poorly known. We aimed to study the involvement of HDM in the initial events that would promote sensitization through the oral route and eventually lead to allergy development. METHODS AND RESULTS: BALB/c mice were exposed intragastrically to proteolytically active and inactive HDM, as such, or in combination with egg white (EW), and inflammatory and type 2 responses were evaluated. Oral administration of HDM, by virtue of its proteolytic activity, promoted the expression, in the small intestine, of genes encoding tight junction proteins, proinflammatory and Th2-biasing cytokines, and it caused expansion of group 2 innate immune cells, upregulation of Th2 cytokines, and dendritic cell migration and activation. In lymphoid tissues, its proteolytically inactivated counterpart also exerted an influence on the expression of surface DC molecules involved in interactions with T cells and in Th2 cell differentiation, which was confirmed in in vitro experiments. However, in our experimental setting we did not find evidence for the promotion of sensitization to coadministered EW. CONCLUSION: Orally administered HDM upregulates tissue damage factors and also acts as an activator of innate immune cells behaving similarly to potent oral Th2 adjuvants.

IgE-Reactivity Pattern of Tomato Seed and Peel Nonspecific Lipid-Transfer Proteins after in Vitro Gastrointestinal Digestion.

The influence of gastrointestinal digestion on the immunological properties of three different nonspecific lipid-transfer proteins (nsLTPs) described in tomato fruit has been assessed using an in vitro system mimicking the stomach and intestine digestion conditions. Tomato peel/pulp nsLTP, Sola l 3, was degraded after digestion, although the immunoglobulin E (IgE) recognition of intact protein and a 10 kDa band were still observed after 30 min of duodenal digestion in the presence of phosphatidylcholine. The tomato seed nsLTP, Sola l 7, showed a higher stability than the other seed allergen, Sola l 6, during digestion. Sola l 7 showed an IgE immunoreactive 6.5 kDa band in immunoblotting analysis, retaining up to 7% of its IgE-binding capacity in inhibition ELISA test after 60 min of duodenal digestion and keeping intact its ability to activate basophils after digestion. These results suggest that the tomato seed allergen Sola l 7 might be considered as an important allergen in the induction of allergic responses to tomato due to its high stability against gastrointestinal digestion.

Percepción de los usuarios de la farmacia comunitaria sobre la COVID-19 / Community pharmacy users' perception of COVID-19

OBJETIVOS: evaluar la percepción de los usuarios de las farmacias sobre la repercusión de la pandemia COVID-19 en su salud, el conocimiento sobre su posible inclusión en grupos de riesgo y su actitud ante una posible vacuna. MATERIAL Y MÉTODOS: estudio observacional transversal aleatorizado, en farmacias de Pontevedra y Ourense, desde marzo a junio de 2020 al comienzo y después de la restricción de movimientos. Sujetos: usuarios ≥ 18 años que acuden a las farmacias participantes en demanda de medicamentos y/o material de higiene y protección. Procedimiento: el usuario cumplimentaba un cuestionario anónimo, depositándolo hasta la noche en una bandeja de plástico desinfectada diariamente. El procedimiento se repetirá tras cesar el confinamiento. Resultados de la primera fase: se realizaron 706 encuestas. 415 (58,8 %) mujeres, edad media 48,9 (DE=16,9) años. 100 participantes (14,2 %) viven solos.637 (90,2 %) creen que la COVID-19 es más peligrosa que la gripe, 189 (26,8 %) desconocen estar en algún grupo de riesgo. 107 (15,1 %) dicen sentirse mal o muy mal con el aislamiento. Los aspectos más afectados son: familiar 350 (49,6 %) y emocional 338 (47,9 %). En 2019/20 se vacunaron de la gripe 172 (24,4 %) y en 2020/21 piensan vacunarse 243 (34,4 %). 448 (63,5 %) se vacunarán frente a la COVID-19 cuando exista vacuna, esté o no financiada por el Sistema Nacional de Salud, 183 (25,9 %) se lo pensarán. CONCLUSIONES: los encuestados consideran la COVID-19 más peligrosa que la gripe estacional. En esta primera fase la afectación sobre bienestar y salud no parece elevada. Un alto porcentaje se vacunará frente a la COVID-19

AIMS: to assess the pharmacy users' perception on the impact of the COVID-19 pandemic on their health, the knowledge of their possible inclusion in risk groups and their attitude towards a potential vaccine. MATERIAL AND METHODS: Randomized, cross-sectional, observational study in pharmacies of Pontevedra and Ourense, from March to June 2020 at the beginning and after movement restrictions. Subjects: users ≥ 18 years old who go to the participating pharmacies to purchase medicines and/or hygiene and protection material. Procedure: the user completed an anonymous questionnaire, which was then placed until night in a plastic tray that was disinfected daily. The procedure will be repeated after the confinement has been terminated. Results of the first phase: 706 surveys were conducted. 415 (58.8%) women, aged 48.9 9 years on average (SD=16.9). 100 participants (14.2%) live alone. 637 (90.2%) believe that COVID-19 is more dangerous than influenza, 189 (26.8%) don't know if they belong to any risk group. 107 (15.1%) say they feel bad or very bad about isolation. The most affected aspects are: familiar 350 (49.6%) and emotional 338 (47.9%). In 2019/20, 172 (24.4%) were vaccinated against influenza and in 2020/21 243 (34.4%) are planning to get vaccinated. 448 (63.5%) will be vaccinated against COVID-19 when the vaccine is available, whether or not it is financed by the National Health System, and 183 (25.9%) will think about it. CONCLUSIONS: respondents consider COVID-19 more dangerous than seasonal influenza. In this first phase, the impact on well-being and health does not seem to be high. A high percentage of people will be vaccinated against COVID-19

Ovalbumin-Derived Peptides Activate Retinoic Acid Signalling Pathways and Induce Regulatory Responses Through Toll-Like Receptor Interactions.

This study investigates the potential of a hydrolysate of ovalbumin with pepsin (OP) to preclude Th2-type immunity by the enhancement of tolerogenic dendritic cells (DCs) and regulatory T (Treg) cells. Through Toll-like receptor (TLR) stimulation, OP enhances the retinoic acid pathway on DCs by means of the induction of aldehyde dehydrogenase enzymes and transforming growth factor beta (TGF-ß), and it confers upon DC the ability to upregulate interleukin 10 (IL-10) as well as other tolerance-promoting mediators downstream of TRL signalling, such as IL-27, IL-33, Notch ligands, OX40L, and the transcription factors IRF4 and IRF8. OP-conditioned DCs induce the expansion of Foxp3+ and Tr1 cells in co-culture with CD4+ T cells. Furthermore, OP directly conditions CD4+ T cells from naïve mice, without the mediation of DCs, to express aldehyde dehydrogenase (ALDH) enzymes and, in the presence of the Th2 cytokine IL-4 and exogenous TGF-ß, it enhances Foxp3 expression. It is noteworthy that, on CD4+ T cells isolated from egg-allergic mice, OP significantly enriches the levels of Foxp3+ and Foxp3+ RORγt+ CD4+ T cells. In conclusion, we show that food peptides may work, analogously to microbial-driven signals, through TLRs, to promote a tolerogenic phenotype on cells of the innate and adaptive immune system, a property that is further enhanced in the context of a Th2 cytokine-rich environment.