Infection control in long term care institutions for the elderly: A reflection document on the situation in Spain

A progressively increasing percentage of the elderly live during the last years of their lives in nursing homes. Although these institutions are intended to mimic life at home as much as possible, they have characteristics that make them quite similar to a “nosocomiun”, i.e. an establishment for the treatment of the sick. The very coexistence among the elderly, the fact of sharing caregivers and the very significant exposure to third parties, together with the frequent predisposing diseases to infection in this population, make infection frequent among residents and also easily transmissible. This leads us to ask what can be done to prevent infection in this environment and more specifically what is the state of the art of the matter in a Western European nation such as ours. The Board of Trustees of the Health Sciences Foundation has asked itself a series of questions on the subject of infection prevention in Nursing Homes, the structure of procedures, the legislation available, compliance with the measures indicated, the best indicators of the processes and therefore, the need to promote in Spain a document of recommendations to avoid infections in this poplation whose morbidity and mortality need not be highlighted. To this end, a multidisciplinary group of experts in different aspects of this problem has been convened and asked the proposed questions. The questions were discussed by the group as a whole and led to a series of conclusions agreed upon by the participants. The results of the meeting are reported below (AU)

Un porcentaje progresivamente creciente de las personas mayores viven durante los últimos años de su vida en residencias de ancianos. Dichas instituciones, aunque pretenden remedar lo más posible la vida en el hogar, tienen características que las hace bastante parecidas a un nosocomio, es decir a un establecimiento destinado al tratamiento de enfermos. La propia convivencia entre los ancianos, el hecho de compartir cuidadores y la exposición muy importante a terceras personas, junto con las frecuentes enfermedades predisponentes a la infección de esta población, hacen que la infección sea frecuente entre los residentes y que además sea fácilmente transmisible. Esto nos lleva a preguntarnos qué puede hacerse para prevenir la infección en este medio y más concretamente cuál es el estado del arte de la cuestión en una nación de Europa Occidental como la nuestra. El patronato de la Fundación de Ciencias de la Salud se ha formulado una serie de preguntas sobre el tema de la prevención de la infección en las Residencias de Mayores, la estructura de la misma, la legislación vigente, el cumplimiento de las medidas indicadas, los indicadores de los procesos y por ende, la necesidad de fomentar en España un documento de recomendaciones para evitar infecciones en esta población cuya morbilidad y mortalidad no necesitan ser resaltadas. Para ello, se ha convocado a un grupo multidisciplinar de expertos en distintos aspectos de este problema a los que se les han formulado las preguntas propuestas. Las preguntas han sido discutidas por el grupo en su conjunto y han conducido a una serie de conclusiones consensuadas entre los participantes. Pasamos, a continuación a relatar los resultados de la reunión (AU)

Opitz GBBB syndrome with total anomalous pulmonary venous connection: A new MID1 gene variant.

BACKGROUND: Opitz GBBB syndrome (GBBB) is an X-linked disease characterized by midline defects, including congenital heart defects. We present our diagnostic approach to the identification of GBBB in a consanguineous family in which two males siblings were concordant for a total anomalous connection of pulmonary veins and minor facial dysmorphias. METHODS: Targeted exome sequencing analysis of a 380-gene panel associated with cardiovascular disease was performed on the propositus. Interpretative analysis of the exome results was conducted, and 3D models of the protein changes were generated. RESULTS: We identified a NM_000381.4:c.608G>A;p.(Arg203Gln) change in MID1, affecting the conformation of the B-box 2 domain of the protein, with a zinc finger structure and associated protein interactions. This clinical phenotype is consistent with GBBB; however, the type of congenital heart disease observed in this case has not been previously reported. CONCLUSION: A new likely pathogenic variant on MID1 c.608G>A was found to be associated with Opitz GBBB syndrome.

Impact of the COVID-19 pandemic on the mental health of the general population and health care workers / Impacto de la pandemia de COVID-19 en la salud mental de la población general y de los trabajadores sanitarios

The Health Sciences Foundation has assembled a multidisciplinary group around a series of questions about the impact of the COVID-19 pandemic on the mental health of the general population and specific groups within that population, particularly healthcare workers.In the general population, the most prevalent mental disorders have been anxiety, sleep disorders and affective disorders, primarily depression. There has been a considerable increase in suicidal behavior, especially in young women and men over 70 years of age. There has been an increase in alcohol abuse and nicotine, cannabis and cocaine use. In contrast, the use of synthetic stimulants during periods of confinement has decreased. With regard to non-substance addictions, gambling was very limited, pornography consumption increased significantly and there was an increase in compulsive shopping and the use of video games.Particularly vulnerable groups include adolescents and patients with autism spectrum disorders. Healthcare workers suffered an increase in depression, anxiety and post-traumatic stress, especially those who were exposed during the early stages of the pandemic. Female sex, being a nurse, proximity to patients with COVID-19, working in a rural environment and having previous psychiatric or organic illnesses were some of the most frequently repeated factors in various studies in this population group.The media have shown a good degree of knowledge about these problems and have dealt with them frequently and from the point of view of ethics, crisis situations, such as the one experienced, have triggered not only physical but also moral claudications. (AU)

La Fundación de Ciencias de la Salud ha reunido a un grupo multidisciplinar alrededor de una serie de preguntas sobre el impacto de la pandemia de COVID-19 en la salud mental de la población en general y de grupos específicos de dicha población, particularmente los trabajadores sanitarios.En la población general, los trastornos mentales más prevalentes han sido la ansiedad, los trastornos del sueño y los trastornos afectivos, fundamentalmente la depresión. Se ha producido un aumento considerable de la conducta suicida, especialmente en mujeres jóvenes y varones mayores de 70 años. Se ha incrementado el abuso de alcohol y los consumos de nicotina, cannabis y cocaína.Por el contrario, ha disminuido el consumo de los estimulantes sintéticos durante los periodos de confinamiento. Respecto a las adicciones sin sustancia, el juego de apuestas quedó muy limitado, el consumo de pornografía experimentó un incremento notable y hubo un aumento de la compra compulsiva y del uso de videojuegos.En cuanto a grupos particularmente vulnerables hay que destacar el de los adolescentes y el de los enfermos con trastornos del espectro autista. Los sanitarios han sido un grupo especialmente vulnerable, en particular los que estuvieron expuestos durante las primeras fases de la pandemia. El sexo femenino, el ser enfermera, la proximidad a los pacientes con COVID-19, el ejercicio en un medio rural y padecer enfermedades psiquiátricas u orgánicas previas, fueron algunos de los factores más frecuentemente repetidos en diversos estudios en este grupo de población. Depresión, ansiedad y estrés post-traumático fueron los trastornos más frecuentes.Los medios de comunicación han mostrado un buen grado de conocimiento sobre estos problemas y los han tratado con frecuencia. Desde el prisma de la ética, las situaciones de crisis, como la vivida, han desencadenado claudicaciones no solo físicas sino también morales. (AU)

Impact of the COVID-19 pandemic on the diagnosis and treatment of onco-hematologic patients: a discussion paper / Impacto de la pandemia de COVID-19 en el diagnóstico y tratamiento de los pacientes onco-hematológicos: un documento de opinión

We do not know the precise figure for solid organ tumors diagnosed each year in Spain and it is therefore difficult to calculate whether there has been a decrease in cancer diagnoses as a consequence of the pandemic. Some indirect data suggest that the pandemic has worsened the stage at which some non-hematological neoplasms are diagnosed. Despite the lack of robust evidence, oncology patients seem more likely to have a poor outcome when they contract COVID-19. The antibody response to infection in cancer patients will be fundamentally conditioned by the type of neoplasia present, the treatment received and the time of its administration.In patients with hematological malignancies, the incidence of infection is probably similar or lower than in the general population, due to the better protective measures adopted by the patients and their environment. The severity and mortality of COVID-19 in patients with hematologic malignancies is clearly higher than the general population. Since the immune response to vaccination in hematologic patients is generally worse than in comparable populations, alternative methods of prevention must be established in these patients, as well as actions for earlier diagnosis and treatment.Campaigns for the early diagnosis of malignant neoplasms must be urgently resumed, post-COVID manifestations should be monitored, collaboration with patient associations is indisputable and it is urgent to draw the right conclusions to improve our preparedness to fight against possible future catastrophes. (AU)

No conocemos con precisión la cifra nacional de tumores sólidos diagnosticados en España anualmente y por tanto se hace difícil calcular si ha habido una disminución de diagnósticos de cáncer como consecuencia de la pandemia. Algunos datos indirectos permiten sospechar que la pandemia ha empeorado el estadio en que se diagnostican algunas neoplasias no hematológicas. A pesar de no existir una evidencia robusta, los pacientes oncológicos presentan una mayor tendencia a tener una mala evolución cuando contraen COVID-19. La respuesta de anticuerpos frente a la infección en pacientes con cáncer va a estar condicionada fundamentalmente por el tipo de neoplasia presente, el tratamiento recibido y el momento de su administración.En pacientes con hemopatías malignas la incidencia de infección es probablemente similar o inferior a la de la población general, debido a las mejores medidas de protección adoptadas por los pacientes y su entorno. La gravedad y letalidad de la COVID-19 en pacientes con hemopatías malignas es claramente más elevada que en la población general. Dado que la respuesta inmune a la vacunación es peor que en poblaciones comparables, hay que establecer métodos alternativos de prevención en estos pacientes, así como planes de diagnóstico y tratamiento precoces.Hay que retomar las campañas de diagnóstico precoz de neoplasias malignas con urgencia, vigilar las manifestaciones post-COVID, colaborar con las asociaciones de pacientes y hacer planes urgentes para hacer frente con más eficiencia a potenciales catástrofes futuras. (AU)

Exploring the druggability of the binding site of aurovertin, an exogenous allosteric inhibitor of FOF1-ATP synthase.

In addition to playing a central role in the mitochondria as the main producer of ATP, FOF1-ATP synthase performs diverse key regulatory functions in the cell membrane. Its malfunction has been linked to a growing number of human diseases, including hypertension, atherosclerosis, cancer, and some neurodegenerative, autoimmune, and aging diseases. Furthermore, inhibition of this enzyme jeopardizes the survival of several bacterial pathogens of public health concern. Therefore, FOF1-ATP synthase has emerged as a novel drug target both to treat human diseases and to combat antibiotic resistance. In this work, we carried out a computational characterization of the binding sites of the fungal antibiotic aurovertin in the bovine F1 subcomplex, which shares a large identity with the human enzyme. Molecular dynamics simulations showed that although the binding sites can be described as preformed, the inhibitor hinders inter-subunit communications and exerts long-range effects on the dynamics of the catalytic site residues. End-point binding free energy calculations revealed hot spot residues for aurovertin recognition. These residues were also relevant to stabilize solvent sites determined from mixed-solvent molecular dynamics, which mimic the interaction between aurovertin and the enzyme, and could be used as pharmacophore constraints in virtual screening campaigns. To explore the possibility of finding species-specific inhibitors targeting the aurovertin binding site, we performed free energy calculations for two bacterial enzymes with experimentally solved 3D structures. Finally, an analysis of bacterial sequences was carried out to determine conservation of the aurovertin binding site. Taken together, our results constitute a first step in paving the way for structure-based development of new allosteric drugs targeting FOF1-ATP synthase sites of exogenous inhibitors.

Air pollution and health prevention: A document of reflection / Calidad del aire ambiente y prevención de la salud: Un documento de reflexión

Ambient air quality, pollution and its implication onhealth is a topic of enormous importance that is normallydealt with by major specialists in their particular areas of interest. In general, it is not discussed from multidisciplinary approaches or with a language that can reach everyone. For thisreason, the Health Sciences Foundation, from its preventionarea, has formulated a series of questions to people with veryvaried competences in the area of ambient air quality in orderto obtain a global panorama of the problem and its elementsof measurement and control. The answers have been produced by specialists in each subject and have been subjected to ageneral discussion that has allowed conclusions to be reached on each point. The subject was divided into three main blocks:external ambient air, internal ambient air, mainly in the workplace, and hospital ambient air and the consequences of itspoor control. Along with the definitions of each area and theindicators of good and bad quality, some necessary solutionshave been pointed out. We have tried to know the current legislation on this problem and the competences of the differentadministrations on it. Despite its enormous importance, ambient air quality and health is not usually a topic of frequentpresence in the general media and we have asked about thecauses of this. Finally, the paper addresses a series of reflections from the perspective of ethics and very particularly in thelight of the events that the present pandemic raises. This workaims to provide objective data and opinions that will enablenon-specialists in the field to gain a better understanding ofthis worrying reality. (AU)

La calidad del aire ambiente y su implicación en la salud esun tema de enorme importancia que normalmente es tratadopor grandes especialistas en sus particulares áreas de interés.En general, no es discutido desde enfoques multidisciplinaresni con un lenguaje que pueda llegar a todos. Por ese motivo, laFundación de Ciencias de la Salud desde su área de prevención,ha formulado una serie de preguntas a personas con competencias muy variadas en el área de la calidad del aire ambientepara obtener un panorama global del problema y de sus elementos de medida y control. Las respuestas han sido producidas por especialistas en cada tema y han sido sometidas a unadiscusión general que ha permitido alcanzar conclusiones encada punto. El tema ha sido dividido en tres grandes bloques:el aire ambiente externo, el aire ambiente interno, principalmente en el medio laboral, y el aire ambiente hospitalario ylas consecuencias de su mal control. Junto con las definicionesde cada área y los indicadores de buena y mala calidad, se haapuntado a algunas necesarias soluciones. Hemos tratado deconocer la legislación vigente sobre este problema y las competencias de las distintas administraciones sobre el mismo.Pese a su enorme importancia, la calidad del aire ambiente yla salud no suele ser un tema de frecuente presencia en losmedios de comunicación generales y hemos preguntado sobrelas causas de ello. Finalmente, el documento aborda una seriede reflexiones desde la perspectiva de la ética y muy particularmente a la luz de los acontecimientos que la presente pandemia plantea. Este trabajo pretende aportar datos objetivos yopinión que permitan a los no especialistas en el tema conocermejor esta preocupante realidad. (AU)

Ficolin activation as a potential biomarker of the severity of schizophrenia.

Several studies have examined the complement system in schizophrenia, suggesting an involvement of the lectin pathway. We analyzed 49 patients with schizophrenia and explored the association between psychopathology of schizophrenia and complement component 3 (C3) serum levels, C-reactive protein (CRP) serum levels, ficolin activation, and mannose-binding lectin (MBL) activation. In the multiple regression analysis, a negative association was observed between the Positive and Negative Syndrome Scale (PANSS) total score and ficolin activation. Body mass index (BMI) was positively associated with the serum levels of C3 and CRP. MBL activation was not associated with any independent variables. Our findings facilitate a better understanding of the complement system in schizophrenia. Additional studies with a large sample population are needed to confirm our results.

Expanding the Structural Diversity of DNA Methyltransferase Inhibitors.

Inhibitors of DNA methyltransferases (DNMTs) are attractive compounds for epigenetic drug discovery. They are also chemical tools to understand the biochemistry of epigenetic processes. Herein, we report five distinct inhibitors of DNMT1 characterized in enzymatic inhibition assays that did not show activity with DNMT3B. It was concluded that the dietary component theaflavin is an inhibitor of DNMT1. Two additional novel inhibitors of DNMT1 are the approved drugs glyburide and panobinostat. The DNMT1 enzymatic inhibitory activity of panobinostat, a known pan inhibitor of histone deacetylases, agrees with experimental reports of its ability to reduce DNMT1 activity in liver cancer cell lines. Molecular docking of the active compounds with DNMT1, and re-scoring with the recently developed extended connectivity interaction features approach, led to an excellent agreement between the experimental IC50 values and docking scores.

Cell-Permeable Bak BH3 Peptide Induces Chemosensitization of Hematologic Malignant Cells.

Hematologic malignancies such as leukemias and lymphomas are among the leading causes of pediatric cancer death worldwide, and although survival rates have improved with conventional treatments, the development of drug-resistant cancer cells may lead to patient relapse and limited possibilities of a cure. Drug-resistant cancer cells in these hematologic neoplasms are induced by overexpression of the antiapoptotic B-cell lymphoma 2 (Bcl-2) protein families, such as Bcl-XL, Bcl-2, and Mcl-1. We have previously shown that peptides from the BH3 domain of the proapoptotic Bax protein that also belongs to the Bcl-2 family may antagonize the antiapoptotic activity of the Bcl-2 family proteins, restore apoptosis, and induce chemosensitization of tumor cells. Furthermore, cell-permeable Bax BH3 peptides also elicit antitumor activity and extend survival in a murine xenograft model of human B non-Hodgkin's lymphoma. However, the activity of the BH3 peptides of the proapoptotic Bak protein of the Bcl-2 family against these hematologic malignant cells requires further characterization. In this study, we report the ability of the cell-permeable Bak BH3 peptide to restore apoptosis and induce chemosensitization of acute lymphoblastic leukemia and non-Hodgkin's lymphoma cell lines, and this event is enhanced with the coadministration of cell-permeable Bax BH3 peptide and represents an attractive approach to improve the patient outcomes with relapsed or refractory hematological malignant cells.

Molecular dynamics of the histamine H3 membrane receptor reveals different mechanisms of GPCR signal transduction.

In this work, we studied the mechanisms of classical activation and inactivation of signal transduction by the histamine H3 receptor, a 7-helix transmembrane bundle G-Protein Coupled Receptor through long-time-scale atomistic molecular dynamics simulations of the receptor embedded in a hydrated double layer of dipalmitoyl phosphatidyl choline, a zwitterionic polysaturated ordered lipid. Three systems were prepared: the apo receptor, representing the constitutively active receptor; and two holo-receptors-the receptor coupled to the antagonist/inverse agonist ciproxifan, representing the inactive state of the receptor, and the receptor coupled to the endogenous agonist histamine and representing the active state of the receptor. An extensive analysis of the simulation showed that the three states of H3R present significant structural and dynamical differences as well as a complex behavior given that the measured properties interact in multiple and interdependent ways. In addition, the simulations described an unexpected escape of histamine from the orthosteric binding site, in agreement with the experimental modest affinities and rapid off-rates of agonists.

The situation of infection in the elderly in Spain: a multidisciplinary opinion document / Situación de la infección en el anciano: un documento multidisciplinar de opinión

Infection in the elderly is a huge issue whose treatment usually has partial and specific approaches. It is, moreover, one of the areas where intervention can have the most success in improving the quality of life of older patients. In an attempt to give the widest possible focus to this issue, the Health Sciences Foundation has convened experts from different areas to produce this position paper on Infection in the Elderly, so as to compare the opinions of expert doctors and nurses, pharmacists, journalists, representatives of elderly associations and concluding with the ethical aspects raised by the issue. The format is that of discussion of a series of pre-formulated questions that were discussed by all those present. We begin by discussing the concept of the elderly, the reasons for their predisposition to infection, the most frequent infections and their causes, and the workload and economic burden they place on society. We also considered whether we had the data to estimate the proportion of these infections that could be reduced by specific programmes, including vaccination programmes. In this context, the limited presence of this issue in the media, the position of scientific societies and patient associations on the issue and the ethical aspects raised by all this were discussed

La infección en los ancianos es un tema enorme que suele recibir enfoques muy específicos pero parciales. Además, es una de las áreas en las que la intervención podría tener más éxito para mejorar la calidad de vida de los pacientes mayores. En un intento de dar el mayor enfoque posible a este tema, la Fundación de Ciencias de la Salud ha convocado a expertos de diferentes áreas para elaborar este documento de opinión sobre la situación de la infección en los ancianos, tratando de comparar las opiniones de médicos expertos, enfermeras, farmacéuticos, periodistas, representantes de asociaciones de ancianos y terminando con los aspectos éticos que plantea el problema. El formato es el de la discusión de una serie de preguntas preformuladas que fueron discutidas entre todos los presentes. Empezamos discutiendo el concepto de "anciano", las razones de la predisposición a la infección, las infecciones más frecuentes y sus causas, y la carga laboral y económica que suponen para la sociedad. También preguntamos si teníamos datos para estimar la proporción de estas infecciones que podrían ser reducidas por programas específicos, incluyendo programas de vacunación. En este contexto, se discutió la baja presencia de este problema en los medios de comunicación, la posición de las asociaciones científicas y de pacientes sobre el problema y los aspectos éticos que todo esto plantea

Chronic obstructive pulmonary disease (COPD) in Spain and the different aspects of its social impact: a multidisciplinary opinion document / Enfermedad Pulmonar Obstructiva Crónica (EPOC) y diferentes aspectos de su impacto social: un documento multidisciplinar de opinión

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent diseases in the World, and one of the most important causes of mortality and morbidity. In adults 40 years and older, it affects more than 10% of the population and has enormous personal, family and social burden. Tobacco smoking is its main cause, but not the only one, and there is probably a genetic predisposition that increases the risk in some patients. The paradigm of this disease is changing in Spain, with an increase of women that has occurred in recent years. Many of the physio pathological mechanisms of this condition are well known, but the psychological alterations to which it leads, the impact of COPD on relatives and caregivers, the limitation of daily life observed in these patients, and the economic and societal burden that they represent for the health system, are not so well-known. A major problem is the high under-diagnosis, mainly due to difficulties for obtaining, in a systematic way, spirometries in hospitals and health-care centers. For this reason, the Fundación de Ciencias de la Salud and the Spanish National Network Center for Research in Respiratory Diseases (CIBERES) have brought together experts in COPD, patients and their organizations, clinical psychologists, experts in health economics, nurses and journalists to obtain their opinion about COPD in Spain. They also discussed the scientific bibliometrics on COPD that is being carried out from the CIBERES and speculated on the future of this condition. The format of the meeting consisted in the discussion of a series of questions that were addressed by different speakers and discussed until a consensus conclusion was reached

La enfermedad pulmonar obstructiva crónica (EPOC) es una de las enfermedades más prevalentes en el mundo y una de las causas más importantes de mortalidad y morbilidad. En los adultos de más de 40 años, afecta al menos al 10% de la población y tiene una enorme carga personal, familiar y social. El tabaquismo es su principal causa, pero no la única, y probablemente existe una predisposición genética que aumenta el riesgo en algunos pacientes. El paradigma de esta enfermedad está cambiando en España, con un aumento de la incidencia en mujeres que se ha producido en los últimos años. Muchos de los mecanismos fisiopatológicos de la EPOC son bien conocidos, pero no lo son tanto las alteraciones psicológicas a las que conduce, el impacto de la enfermedad en los familiares y cuidadores, la limitación de la vida cotidiana que se observa en estos pacientes y la carga económica y social que representan para el sistema sanitario. Un problema importante es el elevado infradiagnóstico, debido principalmente a las dificultades para obtener, de forma sistemática, espirometrías en los hospitales y centros de salud. Por este motivo, la Fundación de Ciencias de la Salud y el Centro de Investigación en Enfermedades Respiratorias (CIBERES) han reunido a expertos en EPOC, pacientes y sus organizaciones, psicólogos clínicos, expertos en economía de la salud, enfermeras y periodistas para obtener su opinión sobre la EPOC en España. También se ha hablado de la bibliometría científica sobre la EPOC que se está llevando a cabo desde el CIBERES y se ha especulado sobre el futuro de esta enfermedad. El formato de la reunión consistió en la discusión de una serie de cuestiones que fueron abordadas por diferentes ponentes y discutidas hasta llegar a una conclusión consensuada

Analysis of association between temperament and psychological symptoms using the Affective and Emotional Composite Temperament (AFECT) model: An internet-based survey.

BACKGROUND: Temperamental characteristics have been suggested as potential vulnerability markers or could help differential diagnosis among psychiatric disorders. The current study aimed to explore whether there are specific temperament profiles related to different psychological symptoms, according to the Affective and Emotional Composite Temperament (AFECT) model. METHODS: We used a cross-sectional web-based survey collected from the Brazilian Internet Study on Temperament and Psychopathology (BRAINSTEP). The sample consisted of 16,495 self-selected volunteers assessed with the Affective and Emotional Composite Temperament Scale (AFECTS), Adult Self-Report Inventory (ASRI), and Adult Self-Report Scale (ASRS). RESULTS: All unstable affective temperaments (cyclothymic, dysphoric, and volatile) correlated, in different intensities, with all psychiatric symptoms assessed. Cyclothymic temperament was mainly related to borderline personality symptoms. Dysphoric and volatile temperament showed an association with attention deficit hyperactivity symptoms. Melancholic temperament was associated with major depressive symptoms, and euphoric temperament showed a positive correlation with maniac symptoms. Euthymic and hyperthymic temperaments were negatively correlated with all psychiatric symptoms. In addition, the assessment of the emotional traits of temperament showed that high volition, low anger, low sensitivity, and high control are characteristics that are not related to psychopathology. LIMITATIONS: This study had a cross-sectional design, which does not allow an exact inference of cause and consequence. CONCLUSIONS: Our results suggest that temperament assessment using AFECT model may be relevant to assess the risk of developing psychological symptoms over the time. These results strengthen the theoretical framework that psychiatric disorders may be manifestations of the extremes of affective temperaments.

Live Attenuated Salmonella enterica Expressing and Releasing Cell-Permeable Bax BH3 Peptide Through the MisL Autotransporter System Elicits Antitumor Activity in a Murine Xenograft Model of Human B Non-hodgkin's Lymphoma.

The survival of patients with non-Hodgkin's lymphoma (NHL) has substantially improved with current treatments. Nevertheless, the appearance of drug-resistant cancer cells leads to patient relapse. It is therefore necessary to find new antitumor therapies that can completely eradicate transformed cells. Chemotherapy-resistant cancer cells are characterized by the overexpression of members of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein family, such as Bcl-XL, Bcl-2, and Mcl-1. We have recently shown that peptides derived from the BH3 domain of the pro-apoptotic Bax protein may antagonize the anti-apoptotic activity of the Bcl-2 family proteins, restore apoptosis, and induce chemosensitization of tumor cells. In this study, we investigated the feasibility of releasing this peptide into the tumor microenvironment using live attenuated Salmonella enterica, which has proven to be an ally in cancer therapy due to its high affinity for tumor tissue, its ability to activate the innate and adaptive antitumor immune responses, and its potential use as a delivery system of heterologous molecules. Thus, we expressed and released the cell-permeable Bax BH3 peptide from the surface of Salmonella enterica serovar Typhimurium SL3261 through the MisL autotransporter system. We demonstrated that this recombinant bacterium significantly decreased the viability and increased the apoptosis of Ramos cells, a human B NHL cell line. Indeed, the intravenous administration of this recombinant Salmonella enterica elicited antitumor activity and extended survival in a xenograft NHL murine model. This antitumor activity was mediated by apoptosis and an inflammatory response. Our approach may represent an eventual alternative to treat relapsing or refractory NHL.

Vaccines for the prevention of infections in adults: an opinion paper on the situation in Spain / Vacunas para la prevención de infecciones en adultos: artículo de opinión sobre la situación en España

The childhood immunization schedule is well known and generally well implemented in developed countries. For various reasons, the same is not true of vaccines aimed at preventing infections in adults, in which vaccination coverage is incomplete and generally very deficient. In order to assess the situation of adult vaccination in Spain, the Fundación de Ciencias de la Salud has brought together a series of experts in different fields, including doctors, nurses, representatives of patient associations, health managers and economists, health authorities and journalists to deal with this issue. The format was that of a round table in which a series of questions previously formulated by the coordinators were to be answered and debated. The document presented is not an exhaustive review of the topic, nor is it intended to make recommendations, but only to give a multidisciplinary opinion on topics that could be particularly debatable or controversial. The paper reviews the main vaccine-preventable adult diseases, their clinical and economic impact, the possibilities of reducing them with vaccination programmes and the difficulties in carrying them out. The role of nursing, pharmacy services, patient associations and the health administration itself in changing the current situation was discussed. Prospects for new vaccines were discussed and we speculated on the future in this field. Finally, particularly relevant ethical aspects in decision-making regarding vaccination were discussed, which must be faced by both individuals and states. We have tried to summarize, at the end of the presentation of each question, the environment of opinion that was agreed with all the members of the table

El calendario de vacunación infantil es bien conocido y generalmente bien implementado en los países desarrollados. Por varias razones, no ocurre lo mismo en el caso de las vacunas destinadas a prevenir las infecciones en adultos, en los que la cobertura vacunal es incompleta y generalmente muy deficiente. Con el fin de evaluar la situación de la vacunación de adultos en España, la Fundación de Ciencias de la Salud ha reunido a una serie de expertos en diferentes campos, incluyendo médicos, enfermeras, representantes de asociaciones de pacientes, gestores sanitarios, economistas, autoridades sanitarias y periodistas para discutir este asunto. El formato fue el de una mesa redonda en la que una serie de preguntas, formuladas previamente por los coordinadores, debían ser contestadas y debatidas. El documento presentado no es una revisión exhaustiva del tema, ni tiene por objeto hacer recomendaciones, simplemente pretende dar una opinión multidisciplinar sobre aspectos que pueden ser debatibles o controvertidos. El documento revisa las principales enfermedades de los adultos que pueden prevenirse con vacunas, su impacto clínico y económico, las posibilidades de reducirlos con los programas de vacunación y las dificultades para llevarlos a cabo. Se discutió el papel de la enfermería, la farmacia, los servicios de salud, las asociaciones de pacientes y la propia administración sanitaria para cambiar la situación actual. Se evaluaron las perspectivas para nuevas vacunas y se especuló sobre el futuro en este campo. Por último, se discutieron los aspectos éticos especialmente relevantes en la toma de decisiones con respecto a la vacunación, que deben ser afrontados tanto por los individuos como por los estados. Hemos intentado resumir, al final de la presentación de cada pregunta, la opinión que representaba el consenso de todos los miembros de la mesa

Information on nosocomial infections in the mainstream media: an opinion document / Información sobre las infecciones nosocomiales en los principales medios: un documento de opinión

This paper seeks to explore the reasons for the low impact of nosocomial infection in the mainstream media and the responsibilities of physicians and journalists in terms of this situation. To this end, a small group of 13 experts met for round-table discussions, including physicians with expertise in nosocomial infection, medical lawsuits and ethics, as well as journalists from major mainstream Spanish media outlets. The various participants were asked a series of questions prior to the meeting, which were answered in writing by one of the speakers and discussed during the meeting by the whole group, the aim being to obtain consensual conclusions for each of them. The document was subsequently reviewed, edited and forwarded to all co-authors for their agreement. The opinions expressed are the personal opinions of the participants and not necessarily those of the institutions in which they work or with which they collaborate

Este documento busca explorar las razones del bajo impacto de la infección nosocomial en los medios de comunicación tradicionales y las responsabilidades de los médicos y periodistas en esta situación. Con este fin se realizó una mesa redonda con un pequeño grupo de 13 expertos, incluidos médicos con experiencia en infecciones nosocomiales, legislación médica y ética, así como periodistas de los principales medios de comunicación españoles. Antes de la reunión, se les hicieron una serie de preguntas a los participantes, las cuales fueron respondidas por escrito por cada uno y discutidas durante la reunión por todo el grupo, con el objetivo de obtener conclusiones consensuadas para cada una de ellas. El documento fue posteriormente revisado, editado y enviado a todos los coautores para su acuerdo. Las opiniones expresadas por cada participante son propias y no necesariamente de las instituciones en las que trabajan o con las que colaboran

Biochemical Characterization and Structural Modeling of Fused Glucose-6-Phosphate Dehydrogenase-Phosphogluconolactonase from Giardia lamblia.

Glucose-6-phosphate dehydrogenase (G6PD) is the first enzyme in the pentose phosphate pathway and is highly relevant in the metabolism of Giardialamblia. Previous reports suggested that the G6PD gene is fused with the 6-phosphogluconolactonase (6PGL) gene (6pgl). Therefore, in this work, we decided to characterize the fused G6PD-6PGL protein in Giardialamblia. First, the gene of g6pd fused with the 6pgl gene (6gpd::6pgl) was isolated from trophozoites of Giardialamblia and the corresponding G6PD::6PGL protein was overexpressed and purified in Escherichia coli. Then, we characterized the native oligomeric state of the G6PD::6PGL protein in solution and we found a catalytic dimer with an optimum pH of 8.75. Furthermore, we determined the steady-state kinetic parameters for the G6PD domain and measured the thermal stability of the protein in both the presence and absence of guanidine hydrochloride (Gdn-HCl) and observed that the G6PD::6PGL protein showed alterations in the stability, secondary structure, and tertiary structure in the presence of Gdn-HCl. Finally, computer modeling studies revealed unique structural and functional features, which clearly established the differences between G6PD::6PGL protein from G. lamblia and the human G6PD enzyme, proving that the model can be used for the design of new drugs with antigiardiasic activity. These results broaden the perspective for future studies of the function of the protein and its effect on the metabolism of this parasite as a potential pharmacological target.

Cloning and biochemical characterization of three glucose­6­phosphate dehydrogenase mutants presents in the Mexican population.

The deficiency of glucose­6­phosphate dehydrogenase (G6PD) is one of the most common inborn errors of metabolism worldwide. This congenital disorder generally results from mutations that are spread throughout the entire gene of G6PD. Three single-point mutations for G6PD have been reported in the Mexican population and named Veracruz (Arg365His), G6PD Seattle (Asp282His), and G6PD Mexico DF (Thr65Ala), whose biochemical characterization have not yet been studied. For this reason, in this work we analyzed the putative role of the three mutations to uncover the functional consequences on G6PD activity. To this end, was developed a method to clone, overexpress, and purify recombinant human G6PD. The results obtained from all variants showed a loss of catalysis by 80 to 97% and had a decrease in affinity for both physiological substrates with respect to the wild type (WT) G6PD. Our results also showed that the three mutations affected three-dimensional structure and protein stability, suggesting an unstable structure with low conformational stability that affected its G6PD functionality. Finally, based on the biochemical characterization of the unclassified G6PD Mexico DF, we suggest that this variant could be grouped as a Class I variant, because biochemical data are similar with other Class I G6PDs.

Molecular details of dimerization kinetics reveal negligible populations of transient µ-opioid receptor homodimers at physiological concentrations.

Various experimental and computational techniques have been employed over the past decade to provide structural and thermodynamic insights into G Protein-Coupled Receptor (GPCR) dimerization. Here, we use multiple microsecond-long, coarse-grained, biased and unbiased molecular dynamics simulations (a total of ~4 milliseconds) combined with multi-ensemble Markov state models to elucidate the kinetics of homodimerization of a prototypic GPCR, the µ-opioid receptor (MOR), embedded in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/cholesterol lipid bilayer. Analysis of these computations identifies kinetically distinct macrostates comprising several different short-lived dimeric configurations of either inactive or activated MOR. Calculated kinetic rates and fractions of dimers at different MOR concentrations suggest a negligible population of MOR homodimers at physiological concentrations, which is supported by acceptor photobleaching fluorescence resonance energy transfer (FRET) experiments. This study provides a rigorous, quantitative explanation for some conflicting experimental data on GPCR oligomerization.