Immunotherapies and Future Combination Strategies for Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is often diagnosed at an advanced stage and has a dismal prognosis. Nearly 10 years after the approval of cetuximab, anti-PD1/PD-L1 checkpoint inhibitors are the first drugs that have shown any survival benefit for the treatment on platinum-refractory recurrent/metastatic (R/M) HNSCC. Furthermore, checkpoint inhibitors are better tolerated than chemotherapy. The state of the art in the treatment of R/M HNSCC is changing, thanks to improved results for checkpoint inhibitors. Results for these treatments are also awaited in curative settings and for locally advanced HNSCC. Unfortunately, the response rate of immunotherapy is low. Therefore, the identification of predictive biomarkers of response and resistance to anti-PD1/PD-L1 is a key point for better selecting patients that would benefit the most from immunotherapy. Furthermore, the combination of checkpoint inhibitors with various agents is being currently evaluated to improve the response rate, prolong response duration, and even increase the chances for a cure. In this review, we summarize the most important results regarding immune targeting agents for HNSCC, predictive biomarkers for resistance to immune therapies, and future perspectives

Social participation and quality of health care: the experience of citizens' health representatives in Mexico

OBJETIVO: Analizar la experiencia del aval ciudadano en el sistema de salud mexicano en la mejora de los servicios de salud. METODOS: Estudio de corte cualitativo en ocho estados de México en 2008. Se evaluaron diferentes aspectos del programa nacional para mejorar la calidad de los servicios de salud. Se compara la estrategia de México con otras experiencias en América Latina. RESULTADOS: Se exponen los avances y problemas del funcionamiento del aval ciudadano, figura que promueve la participación social en salud de la población. CONCLUSIONES: El aval ciudadano es una figura con gran potencial para representar a los usuarios en los servicios de salud y transmitir sus demandas de mejora de la calidad de la atención médica.OBJETIVO: Analisar a experiência do aval ciudadano (reforço cidadão) no sistema de saúde mexicano na melhora dos serviços de saúde. MÉTODOS: Estudo de coorte qualitativo em oito estados mexicanos, em 2008. Foram avaliados diferentes aspectos do programa nacional para melhora de qualidade nos serviços de saúde. Compara-se a estratégia no México com outras experiências na América Latina. RESULTADOS: Foram expostos os avanços e problemas de funcionamento do aval ciudadano (reforço cidadão), figura que promove a participação social na saúde da população. CONCLUSÕES: O aval ciudadano (reforço cidadão) é uma figura com grande potencial para representar os usuários dos serviços de saúde e transmitir suas exigências de melhorias na qualidade da atenção médica.OBJECTIVE: This article describes the experience of the aval ciudadano "Citizens' Representative" (CR) in improving the Mexican health care system. METHODS: This is a qualitative study which took place in eight Mexican states in 2008. It evaluates different aspects of a nationwide program to increase the quality of health care services (National Crusade for Quality in Health Services). The Mexican strategy is compared with experiences in other Latin American countries. RESULTS: In this paper, there is the description of achievements and problems encountered by the CR in promoting social participation in the health of the population. CONCLUSIONS: The CR has great influence when representing health service users and passing on their demands for improvements to health care quality

Stereoselective Synthesis of Iminosugar 2-Deoxy(thio)glycosides from Bicyclic Iminoglycal Carbamates Promoted by Cerium(IV) Ammonium Nitrate and Cooperative Brønsted Acid-Type Organocatalysis

The first examples of iminosugar-type 2-deoxy(thio)glycoside mimetics are reported. The key step is the activation of a bicyclic iminoglycal carbamate to generate a highly reactive acyliminium cation. Cerium(IV) ammonium nitrate efficiently promoted the formation of 2-deoxy S-glycosides in the presence of thiols, probably by in situ generation of catalytic HNO3, with complete α-stereoselectivity. Cooperative phosphoric acid/Schreiner's thiourea organocatalysis proved better suited for generating 2-deoxy O-glycosides, significantly broadening the scope of the approach.Ministerio de Economía y Competitividad SAF201676083-RMinisterio de Ciencia, Innovación y Universidades RTI2018-097609-B-C21European Cooperation in Science and Technology CA18132Consejo Europeo de Investigación ERC-COG: 64823

SESAR Joint Undertaking report 2010

Abstract Salmonellosis is a gastrointestinal disease caused by non-typhoidal Salmonella serovars such as Salmonella Typhimurium. This pathology is a zoonosis, and food animals with subclinical infection constitute a vast reservoir for disease. After intestinal colonization, Salmonella Typhimurium reaches mesenteric lymph nodes (MLN), where infection is controlled avoiding systemic spread. Although the molecular basis of this infection has been extensively studied, little is known about how microRNA (miRNA) regulate the expression of proteins involved in the Salmonella-host interaction. Using small RNA-seq, we examined expression profiles of MLN 2 days after infection with Salmonella Typhimurium, and we found 110 dysregulated miRNA. Among them, we found upregulated miR-21, miR-155, miR-150, and miR-221, as well as downregulated miR-143 and miR-125, all of them previously linked to other bacterial infections. Integration with proteomic data revealed 30 miRNA potentially regulating the expression of 15 proteins involved in biological functions such as cell death and survival, inflammatory response and antigenic presentation. The inflammatory response was found increased via upregulation of miRNA such as miR-21 and miR-155. Downregulation of miR-125a/b, miR-148 and miR-1 were identified as potential regulators of MHC-class I components PSMB8, HSP90B1 and PDIA3, respectively. Furthermore, we confirmed that miR-125a is a direct target of immunoproteasome component PSMB8. Since we also found miR-130 downregulation, which is associated with upregulation of HSPA8, we suggest induction of both MHC-I and MHC-II antigen presentation pathways. In conclusion, our study identifies miRNA that could regulate critical networks for antigenic presentation, inflammatory response and cytoskeletal rearrangements

Temperature-related excess mortality in German cities at 2 °C and higher degrees of global warming

Background: Investigating future changes in temperature-related mortality as a function of global mean temperature (GMT) rise allows for the evaluation of policy-relevant climate change targets. So far, only few studies have taken this approach, and, in particular, no such assessments exist for Germany, the most populated country of Europe. Methods: We assess temperature-related mortality in 12 major German cities based on daily time-series of all-cause mortality and daily mean temperatures in the period 1993–2015, using distributed-lag non-linear models in a two-stage design. Resulting risk functions are applied to estimate excess mortality in terms of GMT rise relative to pre-industrial levels, assuming no change in demographics or population vulnerability. Results: In the observational period, cold contributes stronger to temperature-related mortality than heat, with overall attributable fractions of 5.49% (95%CI: 3.82–7.19) and 0.81% (95%CI: 0.72–0.89), respectively. Future projections indicate that this pattern could be reversed under progressing global warming, with heat-related mortality starting to exceed cold-related mortality at 3 °C or higher GMT rise. Across cities, projected net increases in total temperature-related mortality were 0.45% (95%CI: −0.02–1.06) at 3 °C, 1.53% (95%CI: 0.96–2.06) at 4 °C, and 2.88% (95%CI: 1.60–4.10) at 5 °C, compared to today's warming level of 1 °C. By contrast, no significant difference was found between projected total temperature-related mortality at 2 °C versus 1 °C of GMT rise. Conclusions: Our results can inform current adaptation policies aimed at buffering the health risks from increased heat exposure under climate change. They also allow for the evaluation of global mitigation efforts in terms of local health benefits in some of Germany's most populated cities. © 2020 The Author

Risk factors for suicide in transgender population: a bibliographical review

El suicidio supone la primera causa de muerte no natural en España, y la segunda causa general en la población joven. La pertenencia a un grupo social minoritario aumenta la vulnerabilidad ante el suicidio. Este es el caso del colectivo LGBTIQ+, y concretamente, de las personas trans. El objetivo de este estudio fue revisar la literatura científica referente al suicidio en las personas trans, incluyendo factores de riesgo específicos y de protección para mejorar los programas de prevención e intervención. La literatura localizada para el estudio es escasa, en especial en el ámbito de la prevención y la intervención. Se concluye que este colectivo es más vulnerable ante el suicidio por factores como el estigma social, las diversas situaciones vividas a lo largo del ciclo vital, y los problemas psicológicos asociados. Se ha encontrado que la ideación suicida es frecuente en población trans. Su aparición precoz correlaciona positivamente con la aparición de conductas suicidas, por lo que se propone mejorar los programas de prevención. Entre las intervenciones con mayor eficacia se encuentran las técnicas dirigidas a la autoafirmación de género y la construcción de una red de apoyo social.Suicide is the leading cause of unnatural death in Spain, and the second one in the young population in general. Belonging to a minority social group increases vulnerability to suicide. This is the case of the LGBTIQ+group, and specifically, of transgender people. The aim of this study was to review the scientific literature on suicide in transgender population, including risk and protective factors in order to improve prevention and intervention programmes. The literature located for the study is scarce, especially in the field of prevention and intervention. Its early appearance correlates positively with the appearance of suicidal behaviour, which is why it is proposed to improve prevention programmes. Among the interventions that stand out as most effective are techniques aimed at gender self-affirmation and building a social support network. It is concluded that transgender people are more vulnerable to suicide due to factors such as social stigma, challenging situations experienced throughout the life cycle, and associated psychological problems. Suicidal ideation has been found to be frequent in the transgender population

Factores de riesgo para el suicidio en población trans: una revisión bibliográfica

Suicide is the leading cause of unnatural death in Spain, and the second one in the young population in general. Belonging to a minority social group increases vulnerability to suicide. This is the case of the LGBTIQ+ group, and specifically, of transgender people. The aim of this study was to review the scientific literature on suicide in transgender population, including risk and protective factors in order to improve prevention and intervention programmes. The literature located for the study is scarce, especially in the field of prevention and intervention. It is concluded that transgender people are more vulnerable to suicide due to factors such as social stigma, challenging situations experienced throughout the life cycle, and associated psychological problems. Suicidal ideation has been found to be frequent in the transgender population. Its early appearance correlates positively with the appearance of suicidal behaviour, which is why it is proposed to improve prevention programmes. Among the interventions that stand out as most effective are techniques aimed at gender self-affirmation and building a social support network.El suicidio supone la primera causa de muerte no natural en España, y la segunda causa general en la población joven. La pertenencia a un grupo social minoritario aumenta la vulnerabilidad ante el suicidio. Este es el caso del colectivo LGBTIQ+, y concretamente, de las personas trans. El objetivo de este estudio fue revisar la literatura científica referente al suicidio en las personas trans, incluyendo factores de riesgo específicos y de protección para mejorar los programas de prevención e intervención. La literatura localizada para el estudio es escasa, en especial en el ámbito de la prevención y la intervención. Se concluye que este colectivo es más vulnerable ante el suicidio por factores como el estigma social, las diversas situaciones vividas a lo largo del ciclo vital, y los problemas psicológicos asociados. Se ha encontrado que la ideación suicida es frecuente en población trans. Su aparición precoz correlaciona positivamente con la aparición de conductas suicidas, por lo que se propone mejorar los programas de prevención. Entre las intervenciones con mayor eficacia se encuentran las técnicas dirigidas a la autoafirmación de género y la construcción de una red de apoyo social.&nbsp