Trastornos autoinflamatorios de la queratinización / Autoinflammatory Keratinitzation Diseases

La enfermedad autoinflamatoria de la queratización (AiKD, por sus siglas en inglés) es un concepto clínico novedoso que engloba a las enfermedades que presentan antecedentes genéticos, así como mecanismos patogénicos mixtos de autoinflamación y autoinmunidad, lo que en su conjunto se traducirá en una queratinización aberrante de la piel. Los recientes avances han revelado causas genéticas y/o factores predisponentes para una serie de AiKD, dentro de los que se pueden enumerar la presencia de las mutaciones en el IL36RN, en relación con la psoriasis pustulosa, la acrodermatitis continua y la hidradenitis supurativa; en el CARD14, en relación con la pitiriasis rubra pilaris tipo V y algunas formas de psoriasis pustulosa, y en el NLRP1 en relación con la queratosis liquenoide crónica familiar (KLC, por sus siglas en inglés). Se sospecha que la fisiopatología de la AiKD también estaría presente en algunos trastornos no monogénicos. Se debe de comprender que existe una relación bidireccional entre la inflamación y la queratinización para poder determinar un tratamiento óptimo; así mismo para poder desarrollar nuevos fármacos ambos factores deben de tenerse en cuenta. Probablemente en los próximos años nuevas enfermedades inflamatorias de la queratinización serán incluidas dentro del grupo de las AiKD (AU)

Autoinflammatory keratinization disease (AiKD) is a novel clinical concept encompassing diseases with a genetic background and mixed pathogenic mechanisms of autoinflammation and autoimmunity, leading to an aberrant keratinization of the skin. Recent advances in medical genetics have revealed genetic causes and/or predisposing factors for a number of AiKD's, such as mutations in IL36RN related with pustular psoriasis, acrodermatitis continua and hidradenitis suppurativa, in CARD14 in pityriasis rubra pilaris type V and some forms of pustular psoriasis, and in NLRP1 related with familial keratosis lichenoides chronica (KLC). It is suspected that AiKD pathophysiology would also be involved in non-monogenic disorders. The bidirectional relationship between inflammation and keratinization should be understood in order to outline optimal management, and new drug development should take both targets into account. We assume that new inflammatory keratinization diseases may be recognized as AiKDs in the coming years (AU)

Autoinflammatory keratinitzation diseases (AIKDs. / Trastornos autoinflamatorios de la queratinización.

Autoinflammatory keratinization disease (AiKD) is a novel clinical concept encompassing diseases with a genetic background and mixed pathogenic mechanisms of autoinflammation and autoimmunity, leading to an aberrant keratinization of the skin. Recent advances in medical genetics have revealed genetic causes and/or predisposing factors for a number of AiKD's, such as mutations in IL36RN related with pustular psoriasis, acrodermatitis continua and hidradenitis suppurativa, in CARD14 in pityriasis rubra pilaris type V and some forms of pustular psoriasis, and in NLRP1 related with familial keratosis lichenoides chronica (KLC). It is suspected that AiKD pathophysiology would also be involved in non-monogenic disorders. The bidirectional relationship between inflammation and keratinization should be understood in order to outline optimal management, and new drug development should take both targets into account. We assume that new inflammatory keratinization diseases may be recognized as AiKDs in the coming years.

Algoritmo de tratamiento con omalizumab en urticaria crónica espontánea / Algorithm for Treatment of Chronic Spontaneous Urticaria with Omalizumab

Antecedentes y objetivo: Los ensayos pivotales de omalizumab en urticaria crónica espontánea (UCE) tienen un periodo de tratamiento de entre 12 y 24 semanas. Sin embargo, muchos pacientes en práctica clínica requieren periodos de tratamiento más prolongados. Por ello el objetivo es presentar un algoritmo de manejo del fármaco. Materiales y métodos: El documento de consenso que detallamos nace de la puesta en común, aceptación, revisión y confrontación de la literatura reciente del grupo de trabajo de UCE "Xarxa d'Urticària Catalana i Balear" (XUrCB). Resultados: Se inicia el tratamiento a dosis autorizada y se ajusta la dosis en intervalos trimestrales en función del Urticaria Activity Score de los últimos 7 días (UAS7) y/o el Urticarial Control Test (UCT). Conclusiones: El algoritmo propuesto pretende servir de guía respecto a cómo ajustar dosis, cómo y cuándo parar el fármaco y el modo de reintroducirlo en casos de recaída

Background and objective: Pivotal trials with omalizumab for treatment of chronic spontaneous urticaria (CSU) are generally run over 12 to 24weeks. However, in clinical practice, many patients need longer treatment. In this article, we present an algorithm for treatment with omalizumab. Material and methods: The consensus document we present is the result of a series of meetings by the CSU working group of "Xarxa d'Urticària Catalana i Balear" (XUrCB) at which data from the recent literature were presented, discussed, compared, and agreed upon. Results: Treatment with omalizumab should be initiated at the authorized dose, and is adjusted at 3-monthly intervals according to the Urticaria Activity Score Over 7 days, the Urticaria Control Test, or both. Conclusions: The algorithm proposed is designed to provide guidance on how to adjust omalizumab doses, how and when to discontinue the drug, and how to reintroduce it in cases of relapse

Algorithm for Treatment of Chronic Spontaneous Urticaria with Omalizumab. / Algoritmo de tratamiento con omalizumab en urticaria crónica espontánea.

BACKGROUND AND OBJECTIVE: Pivotal trials with omalizumab for treatment of chronic spontaneous urticaria (CSU) are generally run over 12 to 24weeks. However, in clinical practice, many patients need longer treatment. In this article, we present an algorithm for treatment with omalizumab. MATERIAL AND METHODS: The consensus document we present is the result of a series of meetings by the CSU working group of "Xarxa d'Urticària Catalana i Balear" (XUrCB) at which data from the recent literature were presented, discussed, compared, and agreed upon. RESULTS: Treatment with omalizumab should be initiated at the authorized dose, and is adjusted at 3-monthly intervals according to the Urticaria Activity Score Over 7days, the Urticaria Control Test, or both. CONCLUSIONS: The algorithm proposed is designed to provide guidance on how to adjust omalizumab doses, how and when to discontinue the drug, and how to reintroduce it in cases of relapse.

Cervical cancer cells suppress effector functions of cytotoxic T cells through the adenosinergic pathway.

BACKGROUND: The expression of CD73 in tumor cells plays a significant role in the production of adenosine (Ado) that suppresses antitumor effector cells. METHODS: In this study we analyzed the capability of HPV-positive (HPV+) cervical cancer (CeCa) cell lines CaSki, SiHa, HeLa, and RoVa; and HPV-negative (HPV-) cell lines C33A and ViBo to produce Ado and inhibit effector functions of CD8+ T cells. RESULTS: HPV+ CeCa cells expressed significantly higher levels of CD73 in the membrane (p<0.01) than HPV- CeCa cells and this expression was associated with the production of larger amounts of Ado (>400µM) compared to HPV-CeCa cells (<200µM) in the presence of AMP, as well asa stronger inhibition of (>50%) proliferation, activation, and cytotoxic activity of CD8+ T cells via interaction with A2A adenosine receptor. We also provide evidence that silenced E6/E7 expression in CeCa cells, strongly reduced its CD73 expression level and its capability to generate Ado. CONCLUSION: This results suggest that HPV infection, which is associated with more than 99% of CeCa cases, may present an increased constitutive expression of CD73 in cervical neoplasia to contribute to the suppression of the immune response mediated by the production of large amounts of Ado.

Shared decision-making in the care of individuals with diabetes.

People with diabetes often live with other chronic conditions and lead complicated lives. Determining what is the best management decision for a patient requires consideration of each individual's personal, social and biomedical context, what he or she values, the reasons he or she has to value the available options, and the relative contribution of each option in terms of benefits, harms, costs and inconveniences. Empathic conversations between patients and clinicians to diagnose the patient situation that necessitates action and the range of evidence-based actions that best address the situation, so-called shared decision-making, are essential to the personalized care of people with diabetes. The aim of the present review was to present key elements of shared decision-making and propose three different approaches for its application. The first approach focuses on transferring information to patients so that they can make decisions. The second approach, choice, focuses on cultivating the individual's ability to give voice to which choice is best for them. The third approach, conversation, establishes an empathic conversational environment through which the individual with diabetes and their clinician think and talk through how to address the problems of living with diabetes and related illnesses. These approaches are manifest in the design of evidence-based decision aids created to support shared decision-making. In randomized trials, decision aids can efficiently improve patient's knowledge, satisfaction, risk awareness, decisional conflict and involvement. Further research, however, is needed to better understand when and how to promote the empathic conversations, patient, clinician and service and policy contexts necessary to routinely implement shared decision-making in different at scale healthcare systems. In the interim, sufficient evidence and tools exist for persons with diabetes and their clinicians to gain expertise in making decisions together.

Particle size distribution and morphological changes in activated carbon-metal oxide hybrid catalysts prepared under different heating conditions.

In catalysis processes, activated carbon (AC) and metal oxides (MOs) are widely used either as catalysts or as catalyst supports because of their unique properties. A combination of AC and a MO in a single hybrid material entails changes not only in the composition, microstructure and texture but also in the morphology, which may largely influence the catalytic behaviour of the resulting product. This work is aimed at investigating the modifications in the morphology and particle size distribution (PSD) for AC-MO hybrid catalysts as a result of their preparation under markedly different heating conditions. From a commercial AC and six MO (Al2O3, Fe2O3, ZnO, SnO2, TiO2 and WO3) precursors, two series of such catalysts are prepared by wet impregnation, oven-drying at 120 ºC, and subsequent heat treatment at 200 ºC or 850 ºC in inert atmosphere. The resulting samples are characterized in terms of their morphology and PSD by scanning electron microscopy and ImageJ processing program. Obtained results indicate that the morphology, PSD and degree of dispersion of the supported catalysts are strongly dependent both on the MO precursor and the heat treatment temperature. With the temperature rise, trends are towards the improvement of crystallinity, the broadening of the PSD and the increase in the average particle size, thus suggesting the involvement of sintering mechanisms. Such effects are more pronounced for the Fe, Sn and W catalysts due to the reduction of the corresponding MOs by AC during the heat treatment at 850 ºC.

Electrical conductivity of activated carbon-metal oxide nanocomposites under compression: a comparison study.

From a granular commercial activated carbon (AC) and six metal oxide (Al2O3, Fe2O3, SnO2, TiO2, WO3 and ZnO) precursors, two series of AC-metal oxide nanocomposites were prepared by wet impregnation, oven-drying at 120 °C, and subsequent heat treatment at 200 or 850 °C in an inert atmosphere. Here, the electrical conductivity of the resulting products was studied under moderate compression. The influence of the applied pressure, sample volume, mechanical work, and density of the hybrid materials was thoroughly investigated. The DC electrical conductivity of the compressed samples was measured at room temperature by the four-probe method. Compaction assays suggest that the mechanical properties of the nanocomposites are largely determined by the carbon matrix. Both the decrease in volume and the increase in density were relatively small and only significant at pressures lower than 100 kPa for AC and most nanocomposites. In contrast, the bulk electrical conductivity of the hybrid materials was strongly influenced by the intrinsic conductivity, mean crystallite size, content and chemical nature of the supported phases, which ultimately depend on the metal oxide precursor and heat treatment temperature. The supported nanoparticles may be considered to act as electrical switches either hindering or favouring the effective electron transport between the AC cores of neighbouring composite particles in contact under compression. Conductivity values as a rule were lower for the nanocomposites than for the raw AC, all of them falling in the range of semiconductor materials. With the increase in heat treatment temperature, the trend is toward the improvement of conductivity due to the increase in the crystallite size and, in some cases, to the formation of metals in the elemental state and even metal carbides. The patterns of variation of the electrical conductivity with pressure and mechanical work were slightly similar, thus suggesting the predominance of the pressure effects rather than the volume ones.