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Following the waning severity of COVID-19 due to vaccination and the development of immunity, the current variants of SARS-CoV-2 often lead to mild upper respiratory tract infections (MURTIs), suggesting it is an appropriate time to review the pathogenesis and treatment of such illnesses. The present article reviews the diverse causes of MURTIs and the mechanisms leading to symptomatic illness. Different symptoms of MURTIs develop in a staggered manner and require targeted symptomatic treatment. A wide variety of remedies for home treatment is available, including over-the-counter drugs and plant-derived substances. Recent pharmacological research has increased the understanding of molecular effects, and clinical studies have shown the efficacy of certain herbal remedies. However, the use of subjective endpoints in these clinical studies may suggest limited validity of the results. In this position paper, the importance of patient-centric outcomes, including a subjective perception of improved well-being, is emphasized. A best practice approach for the management of MURTIs, in which pharmacists and physicians create an improved multi-professional healthcare setting and provide healthcare education to patients, is proposed. Pharmacists act as first-line consultants and provide patients with remedies, considering the individual patient’s preferences towards chemical or plant-derived drugs and providing advice for self-monitoring. Physicians act as second-line consultants if symptoms worsen and subsequently initiate appropriate therapies. In conclusion, general awareness of MURTIs should be increased amongst medical professionals and patients, thus improving their management.

Se presenta el caso clínico de un paciente que asocia tres trastornos de sueño diferentes: narcolepsia, apnea obstructiva del sueño (AOS) y trastorno de conducta del sueño REM. El objetivo es resaltar la importancia de la narcolepsia, una patología infradiagnosticada y que a veces puede quedar enmascarada por otros trastornos de sueño. En este caso, el paciente es diagnosticado inicialmente de AOS, pero dado que persiste con hipersomnolencia diurna debemos descartar otras causas.

Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the rejection of pluripotent stem cell (PSC)-derived products in allogeneic recipients. Disruption of the Beta-2 Microglobulin (B2M) gene eliminates surface expression of all class I molecules, but leaves the cells vulnerable to lysis by natural killer (NK) cells. Here we show that this 'missing-self' response can be prevented by forced expression of minimally polymorphic HLA-E molecules. We use adeno-associated virus (AAV)-mediated gene editing to knock in HLA-E genes at the B2M locus in human PSCs in a manner that confers inducible, regulated, surface expression of HLA-E single-chain dimers (fused to B2M) or trimers (fused to B2M and a peptide antigen), without surface expression of HLA-A, B or C. These HLA-engineered PSCs and their differentiated derivatives are not recognized as allogeneic by CD8+ T cells, do not bind anti-HLA antibodies and are resistant to NK-mediated lysis. Our approach provides a potential source of universal donor cells for applications where the differentiated derivatives lack HLA class II expression.

Dentro de las políticas farmacéuticas, el Estado se ha interesado por la receta médica como documento legal de prescripción y de dispensación de medicamentos y productos sanitarios, contribuyendo a la mejora en la seguridad del paciente. Con el objetivo de medir la cumplimentación de las recetas que llegan a la farmacia comunitaria se realizó un estudio observacional transversal, durante dos meses de 2019, revisando todas las recetas en soporte papel presentadas para su dispensación en cinco farmacias. En ese intervalo se recibieron un total de 33.463 recetas, 30.085 (89,90 %) eran electrónicas y 3.378 (10,10 %) en papel. De estas, 841 (25 %) eran del Sistema Nacional de Salud (SNS), 931 (27 %) de MUFACE, 362 (11 %) de ISFAS, 28 (1 %) de MUGEJU, 201 (6 %) de otras mutuas y 1.015 (30 %) de asistencia sanitaria privada. Cuando se analizó el número y porcentaje de recetas en papel que podían ser dispensadas legalmente, se observó que sólo 130 (65 %) recetas de otras mutuas, 30 (4 %) recetas del SNS y 34 (3 %) recetas privadas estaban correctamente cumplimentadas. Por tanto, sólo 194 de las 3.378 recetas en papel analizadas (6 %) que se han recibido durante dos meses en las cinco farmacias podían ser dispensadas de acuerdo con la ley actual. Cuando las recetas no están correctamente cumplimentadas, con los datos básicos obligatorios, indispensables para la validez de la receta médica, la seguridad del paciente puede verse comprometida y los profesionales sanitarios que prescriben y los que dispensan los medicamentos se exponen a sanciones.

Introducción: La revascularización es un procedimiento actual para dientes necróticos con ápice inmaduro; supone una opción de manejo clínico más conservador con respecto a los tratamientos tradicionales de apicoformación, en el cual, por medio de la inducción de las células madre de la papila dental periapical, se crea un sangrado dentro del conducto radicular, el cual se convierte en un coágulo estable que permite la maduración fisiológica radicular, a la vez que el engrosamiento de las paredes del conducto. El objetivo de este tratamiento es permitir un cierre completo del ápice. Caso clínico: Se presenta el caso de un niño de 7 años de edad con abceso apical en el diente 21, se realiza un tratamiento de revascularización siguiendo la técnica descrita por Hoshino (1996) de apósitos intraconducto con alguna modificación. Siguiendo la teoría descrita por Iwaya en 2001, y Banchs y Trope en 2004, el canal casose desinfecta con abundante irrigación y se rellena con una combinación de pasta bi-antibiótica. Una vez que se completa el protocolo de desinfección, el ápice se irrita mecánicamente para iniciar el sangrado en el canal y producir un coágulo sanguíneo hasta el nivel de la unión cemento-esmalte, colocando Agregado Trióxido Mineral como barrera entre el coágulo y la restauración final. En este caso, la combinación de un canal desinfectado, una matriz en la que podría crecer tejido nuevo y un sello coronal efectivo parece producir el ambiente necesario para una revascularización exitosa. Conclusiones: Bajo las circunstancias de este caso, se puede concluir que el protocolo del tratamiento seguido (regeneración apical y tapón de MTA) es un tratamiento de éxito clínico para conseguir el cierre apical en dientes inmaduros. Este éxito también dependerá de variables como el material de desinfección radicular: el Cloruro Sódico seguido de una solución salina es capaz de desinfectar los conductos sin tener que instrumentar las débiles paredes dentinarias. El uso de pasta bi-antibiótica intracanal utilizada en el caso clínico previene de la pigmentación dental que provocan las tetraciclinas cuando se utilizan en la pasta tri-antibiótica. Se necesitan revisiones de control radiográfico cada 3 meses el primer año y anualmente hasta los 4 años de realizada la revascularización, para comprobar el éxito del tratamiento. Actualmente la regeneración tisular está enfocada hacia el desarrollo de sistemas de cultivo que permitan reproducir células embrionarias hacia tejidos dentales perdidos.

Objetivo: Determinar la prevalencia de RCV entre las personas que acuden a las farmacias de la provincia de Toledo. Determinar la capacidad de las farmacias para valorar el RCV. Material y método: Estudio observacional transversal poblacional de campo en el que se va a estudiar el RCV de la población de la Provincia de Toledo que cumpla con los criterios de inclusión. • Entre 40 y 65 años. • Dar el consentimiento. • Estado cognitivo no deteriorado. • Estar diagnosticado y / o en tratamiento de ninguna o solamente de una de las siguientes patologías: HTA, DP o DMT2. Resultados: Las farmacias detectaron FRCV en más de la mitad de los pacientes. En la valoración del RCV un 3,9% (15) presentaba RCV alto o muy alto y un 48,3% (186) con RCV moderado. Pacientes con diagnóstico previo de alguna de las patologías crónicas a estudio presentaron un incumplimiento del objetivo terapéutico y/o niveles alterados de valores diagnósticos de patologías de las que no habían sido diagnosticados, este es el caso del 61,5% (8) de pacientesDMT2, el 11,7% (9) de pacientes HTA y el 8,8% (5) de pacientes DP que presentan indicadores de riesgo elevado. Conclusión: Concluimos la capacidad real de las farmacias para detectar FRCV entre las personas que acuden a ellas y de evaluar su RCV con fiabilidad. Obtenemos correlación con los resultados con los de la OMS en cuanto al fracaso terapéutico y demostramos el mal control de la población en general sobre patologías relacionadas con el RCV.

Introduction: Revascularization is a current procedure for necrotic teeth with an immature apex; It is a more conservative clinical management option with respect to traditional apicoformation treatments, where, through the induction of the stem cells of the periapical dental papilla, a bleeding is created inside the root canal, which becomes a stable clot that allows the physiological radicular maturation, at the same time as the thickening of the duct walls. The objective of this treatment is to allow a complete closure of the apex. Clinical case: The case of a 7-year-old boy with apical abscess on tooth 21 is presented, a revascularization treatment is performed following the technique described by Hoshino (1996). Following the theory described by Iwaya in 2001, and Banchs and Trope in 2004, using bi-antibiotic paste in the revascularization, and mineral trioxide aggregate as a barrier between the clot and the final restoration. Conclusions: In the last published studies, calcium hydroxide and tri-antibiotic paste have been used as filling materials between phases, to use a bi-antibiotic mixture. Its effectiveness against calcium hydroxide alone has not been proven, which is used again as the only intermediate material between the steps of the revascularization treatment. With this technique we try to achieve a complete root development and thicker walls, thus avoiding the problem of root fracture.

Using an immunohistochemical technique, we have studied the distribution of kynuneric acid (KYNA) and 3-hydroxyanthranilic acid (3-HAA) in a rat brain injury model (trauma). The study was carried out inducing a cerebral ablation of the frontal motor cortex. Two mouse monoclonal specific antibodies previously developed by our group directed against KYNA and 3-HAA were used. In control animals (sham-operated), the expression of both KYNA and 3-HAA was not observed. In animals in which the ablation was performed, the highest number of immunoreactive cells containing KYNA or 3-HAA was observed in the region surrounding the lesion and the number of these cells decreased moving away from the lesion. KYNA and 3-HAA were also observed in the white matter (ipsilateral side) located close to the injured region and in some cells placed in the white matter of the contralateral side. The distribution of KYNA and 3-HAA perfectly matched with the peripheral injured regions. The results found were identical independently of the perfusion date of animals (17, 30 or 54 days after brain injury). For the first time, the presence of KYNA and 3-HAA has been described in a rat trauma model. Moreover, by using a double immunocytochemistry protocol, it has been demonstrated that both metabolites were located in astrocytes. The findings observed suggest that, in cerebral trauma, KYNA and 3-HAA are involved in tissue damage and that these compounds could act, respectively, as a neuroprotector and a neurotoxic. This means that, in trauma, a counterbalance occurs and that a regulation of the indoleamine 2,3 dioxygenase (IDO) pathway could be required after a brain injury in order to decrease the deleterious effects of ending metabolites (the neurotoxic picolinic acid). Moreover, the localization of KYNA and 3-HAA in the contralateral side of the lesion suggests that the IDO pathway is also involved in the sprouting and pathfinding that follows a traumatic brain injury.

The activin receptor-like kinase 1 (ALK-1) is a type I cell-surface receptor for the transforming growth factor-β (TGF-β) family of proteins. Hypertension is related to TGF-β1, because increased TGF-β1 expression is correlated with an elevation in arterial pressure (AP) and TGF-β expression is upregulated by the renin-angiotensin-aldosterone system. The purpose of this study was to assess the role of ALK-1 in regulation of AP using Alk1 haploinsufficient mice (Alk1+/−). We observed that systolic and diastolic AP were significantly higher in Alk1+/− than in Alk1+/+ mice, and all functional and structural cardiac parameters (echocardiography and electrocardiography) were similar in both groups. Alk1+/− mice showed alterations in the circadian rhythm of AP, with higher AP than Alk1+/+ mice during most of the light period. Higher AP in Alk1+/− mice is not a result of a reduction in the NO-dependent vasodilator response or of overactivation of the peripheral renin-angiotensin system. However, intracerebroventricular administration of losartan had a hypotensive effect in Alk1+/− and not in Alk1+/+ mice. Alk1+/− mice showed a greater hypotensive response to the β-adrenergic antagonist atenolol and higher concentrations of epinephrine and norepinephrine in plasma than Alk1+/+ mice. The number of brain cholinergic neurons in the anterior basal forebrain was reduced in Alk1+/− mice. Thus, we concluded that the ALK-1 receptor is involved in the control of AP, and the high AP of Alk1+/− mice is explained mainly by the sympathetic overactivation shown by these animals, which is probably related to the decreased number of cholinergic neurons.

We previously demonstrated that the administration of GH immediately after severe motor cortex injury, in rats, followed by rehabilitation, improved the functionality of the affected limb and reexpressed nestin in the contralateral motor cortex. Here, we analyze whether these GH effects depend on a time window after the injury and on the reexpression of nestin and actin. Injured animals were treated with GH (0.15 mg/kg/day) or vehicle, at days 7, 14, and 35 after cortical ablation. Rehabilitation was applied at short and long term (LTR) after the lesion and then sacrificed. Nestin and actin were analyzed by immunoblotting in the contralateral motor cortex. Giving GH at days 7 or 35 after the lesion, but not 14 days after it, led to a remarkable improvement in the functionality of the affected paw. Contralateral nestin and actin reexpression was clearly higher in GH-treated animals, probably because compensatory brain plasticity was established. GH and immediate rehabilitation are key for repairing brain injuries, with the exception of a critical time period: GH treatment starting 14 days after the lesion. Our data also indicate that there is not a clear plateau in the recovery from a brain injury in agreement with our data in human patients.

Early life stress is a major factor underlying the vulnerability to respond to stressful events later in life. The present study attempted to evaluate the role of prenatal stress affecting the development of stress-related disorders and their reversion by postnatal exposure to Sertraline (SERT), a front-line medication for medication for posttraumatic stress disorder (PTSD) in humans. To achieve this, adult male and female prenatally stressed (PS) or unstressed (Controls) offspring rats, following oral chronic treatment with SERT (5 mg/kg/day; from 1 month to 4 months old), or not, were studied prior to and after a traumatic event. First, anxiety-like behavior during the prepulse inhibition (PPI) test, a modulation of the startle reflex, was examined in all animals. Subsequently, the animals were subjected to a session of mild inescapable footshocks (IS; 0.35 mA, 5 s) in a shuttle box that was followed by 4 days of situational reminders in the aversive context. Prior to the footshocks no effects of PS or SERT were shown, and no changes in PPI and the habituation to the shuttle box were found. After them, PS led animals to exhibit behavioral alterations. When compared to the Controls, PS animals of both sexes displayed less rearing activity in the aversive environment. PS males responded less to footshock delivery and, in most of the animals, fear extinction was impaired. Moreover, the early postnatal exposure to SERT lessened the behavioral impact of PS in females, while in males it had no effect. Current results extend previous data from our laboratory, showing that PS heightened vulnerability to stress later on, and that SERT acts differently in males and females.