ABSTRACT
Recognition of pathogen-associated molecular patterns can trigger the inositol-requiring enzyme 1 α (IRE1α) arm of the endoplasmic reticulum (ER) stress response in innate immune cells. This process maintains ER homeostasis and also coordinates diverse immunomodulatory programs during bacterial and viral infections. However, the role of innate IRE1α signaling in response to fungal pathogens remains elusive. Here, we report that systemic infection with the human opportunistic fungal pathogen Candida albicans induced proinflammatory IRE1α hyperactivation in myeloid cells that led to fatal kidney immunopathology. Mechanistically, simultaneous activation of the TLR/IL-1R adaptor protein MyD88 and the C-type lectin receptor dectin-1 by C. albicans induced NADPH oxidase-driven generation of ROS, which caused ER stress and IRE1α-dependent overexpression of key inflammatory mediators such as IL-1ß, IL-6, chemokine (C-C motif) ligand 5 (CCL5), prostaglandin E2 (PGE2), and TNF-α. Selective ablation of IRE1α in leukocytes, or treatment with an IRE1α pharmacological inhibitor, mitigated kidney inflammation and prolonged the survival of mice with systemic C. albicans infection. Therefore, controlling IRE1α hyperactivation may be useful for impeding the immunopathogenic progression of disseminated candidiasis.
Subject(s)
Candidiasis , Protein Serine-Threonine Kinases , Humans , Animals , Mice , Protein Serine-Threonine Kinases/metabolism , Endoribonucleases/metabolism , Endoplasmic Reticulum Stress , Candida albicans , Toll-Like Receptors/metabolism , Adaptor Proteins, Signal Transducing/metabolismABSTRACT
BACKGROUND: Major gaps remain - especially in low- and middle-income countries - in the realization of comprehensive, community-based mental health care. One potentially important yet overlooked opportunity for accelerating mental health reform lies within emergency situations, such as armed conflicts or natural disasters. Despite their adverse impacts on affected populations' mental health and well being, emergencies also draw attention and resources to these issues and provide openings for mental health service development. CASE DESCRIPTION: Cases were considered if they represented a low- or middle-income country or territory affected by an emergency, were initiated between 2000 and 2010, succeeded in making changes to the mental health system, and were able to be documented by an expert involved directly with the case. Based on these criteria, 10 case examples from diverse emergency-affected settings were included: Afghanistan, Burundi, Indonesia (Aceh Province), Iraq, Jordan, Kosovo, occupied Palestinian territory, Somalia, Sri Lanka, and Timor-Leste. DISCUSSION AND EVALUATION: These cases demonstrate generally that emergency contexts can be tapped to make substantial and sustainable improvements in mental health systems. From these experiences, 10 common lessons learnt were identified on how to make this happen. These lessons include the importance of adopting a longer-term perspective for mental health reform from the outset, and focusing on system-wide reform that addresses both new-onset and pre-existing mental disorders. CONCLUSIONS: Global progress in mental health care would happen more quickly if, in every crisis, strategic efforts were made to convert short-term interest in mental health problems into momentum for mental health reform.
ABSTRACT
Impacto de un protocolo de prevención de úlceras por presión en pacientes de cuidados intensivos. Introducción: las úlceras por presión (UPP) representan una carga sobreagregada a la enfermedad y una menor calidad de vida para el paciente y para los que están a su cuidado, son consideradas además un indicador negativo de la calidad asistencial. Los pacientes en estado crítico poseen factores intrínsecos y extrínsecos que los predisponen con mayor frecuencia a presentar UPP, de aquí la importancia de contar con un protocolo de cuidados de enfermería que permita reducir su incidencia y prevalencia. Objetivo: conocer el impacto de un protocolo de prevención de aparición de úlceras por presión en pacientes de unidades de cuidados intensivos...
Subject(s)
Male , Adolescent , Adult , Humans , Female , Middle Aged , Clinical Protocols , Critical Illness , Practice Guidelines as Topic , Pressure Ulcer/prevention & control , Age Distribution , Chile , Cross-Sectional Studies , Intensive Care Units , Length of Stay , Risk Assessment/methods , Prospective StudiesABSTRACT
Desde tiempos ancestrales, de la mano con el proceso de envejecimiento y la aparición de enfermedades que confinan a los pacientes a permanecer encamados, las úlceras por presión (UPP), han sido el estigma de una iatrogenia en los cuidados.
