Aged lipid-laden microglia display impaired responses to stroke

Microglial cells of the aged brain manifest signs of dysfunction that could contribute to the worse neurological outcome of stroke in the elderly. Treatment with colony-stimulating factor 1 receptor antagonists enables transient microglia depletion that is followed by microglia repopulation after treatment interruption, causing no known harm to mice. We tested whether this strategy restored microglia function and ameliorated stroke outcome in old mice. Cerebral ischemia/reperfusion induced innate immune responses in microglia highlighted by type I interferon and metabolic changes involving lipid droplet biogenesis. Old microglia accumulated lipids under steady state and displayed exacerbated innate immune responses to stroke. Microglia repopulation in old mice reduced lipid-laden microglia, and the cells exhibited reduced inflammatory responses to ischemia. Moreover, old mice with renewed microglia showed improved motor function 2 weeks after stroke. We conclude that lipid deposits in aged microglia impair the cellular responses to ischemia and worsen functional recovery in old mice.© 2022 The Authors. Published under the terms of the CC BY 4.0 license

Catástrofes. Repercusión en Salud Mental.

Sin resumen

Catástrofes. Repercusión en Salud Mental.

Sin resumen

Contribution of microscopy for understanding the mechanism of action against trypanosomatids

Transmission electron microscopy (TEM) has proved to be a useful tool to study the ultrastructural alterations and the target organelles of new antitrypanosomatid drugs. Thus, it has been observed that sesquiterpene lactones induce diverse ultrastructural alterations in both T. cruzi and Leishmania spp., such as cytoplasmic vacuolization, appearance of multilamellar structures, condensation of nuclear DNA, and, in some cases, an important accumulation of lipid vacuoles. This accumulation could be related to apoptotic events. Some of the sesquiterpene lactones (e.g., psilostachyin) have also been demonstrated to cause an intense mitochondrial swelling accompanied by a visible kinetoplast deformation as well as the appearance of multivesicular bodies. This mitochondrial swelling could be related to the generation of oxidative stress and associated to alterations in the ergosterol metabolism. The appearance of multilamellar structures and multiple kinetoplasts and flagella induced by the sesquiterpene lactone psilostachyin C indicates that this compound would act at the parasite cell cycle level, in an intermediate stage between kinetoplast segregation and nuclear division. In turn, the diterpene lactone icetexane has proved to induce the external membrane budding on T. cruzi together with an apparent disorganization of the pericellar cytoskeleton. Thus, ultrastructural TEM studies allow elucidating the possible mechanisms and the subsequent identification of molecular targets for the action of natural compounds on trypanosomatids.Fil: Lozano, Esteban Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Spina Zapata, Renata María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Tonn, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

Spatial and temporal intra-tumoral heterogeneity in advanced HGSOC: Implications for surgical and clinical outcomes.

Limited evidence exists on the impact of spatial and temporal heterogeneity of high-grade serous ovarian cancer (HGSOC) on tumor evolution, clinical outcomes, and surgical operability. We perform systematic multi-site tumor mapping at presentation and matched relapse from 49 high-tumor-burden patients, operated up front. From SNP array-derived copy-number data, we categorize dendrograms representing tumor clonal evolution as sympodial or dichotomous, noting most chemo-resistant patients favor simpler sympodial evolution. Three distinct tumor evolutionary patterns from primary to relapse are identified, demonstrating recurrent disease may emerge from pre-existing or newly detected clones. Crucially, we identify spatial heterogeneity for clinically actionable homologous recombination deficiency scores and for poor prognosis biomarkers CCNE1 and MYC. Copy-number signature, phenotypic, proteomic, and proliferative-index heterogeneity further highlight HGSOC complexity. This study explores HGSOC evolution and dissemination across space and time, its impact on optimal surgical cytoreductive effort and clinical outcomes, and its consequences for clinical decision-making

Untargeted lipidomics uncovers lipid signatures distinguishing severe versus moderate forms of acutely decompensated cirrhosis

BACKGROUND AND AIM: Acutely decompensated of cirrhosis is a heterogeneous clinical entity associated with moderate mortality. In some patients, this condition develops quickly into a more often deadly acute-on-chronic liver failure (ACLF), in which other organs such as the kidneys or brain fail. The aim of this study was to characterize the blood lipidome in a large series of patients with cirrhosis and identify specific signatures associated with acute decompensation and ACLF development. METHODS: Serum untargeted lipidomics was performed in 561 patients with acutely decompensated (AD) cirrhosis (518 without and 43 with ACLF) (discovery cohort) and in 265 AD patients (128 without and 137 with ACLF) in whom serum samples were available to perform repeated measurements during the 28-day follow-up (validation cohort). Analyses were also performed in 78 AD patients included in a therapeutic albumin trial, 43 patients with compensated cirrhosis and 29 healthy subjects. RESULTS: The circulating lipid landscape associated with cirrhosis was characterized by a generalized suppression, which was more manifest during acute decompensation and in non-surviving patients. By computing discriminating accuracy and the variable importance projection score for each of the 223 annotated lipids, we identified a sphingomyelin fingerprint specific for AD cirrhosis and a distinct cholesteryl ester and lysophosphatidylcholine fingerprint for ACLF. Liver dysfunction, mainly, and infections were the principal net contributors to these fingerprints, which were dynamic and interchangeable between AD patients whose condition worsened to ACLF and those who improved. Notably, blood lysophosphatidylcholine levels increased in these patients after albumin therapy. CONCLUSIONS: Our findings provide insights into the lipid landscape associated with decompensation of cirrhosis and ACLF progression and identify unique noninvasive diagnostic biomarkers of advanced cirrhosis. LAY SUMMARY: Analysis of lipids in blood from patients with advanced cirrhosis reveals a general suppression of their levels in the circulation of these patients. A specific group of lipids known as sphingomyelins are useful to distinguish compensated from decompensated patients with cirrhosis. Another group of lipids designated cholesteryl esters further distinguish patients with decompensated patients who are at risk of developing organ failures

Illness perceptions and explanatory models of viral hepatitis B & C among immigrants and refugees: a narrative systematic review.

© 2015 Owiti et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.BACKGROUND: Hepatitis B and C (HBV, HCV) infections are associated with high morbidity and mortality. Many countries with traditionally low prevalence (such as UK) are now planning interventions (screening, vaccination, and treatment) of high-risk immigrants from countries with high prevalence. This review aimed to synthesise the evidence on immigrants' knowledge of HBV and HCV that might influence the uptake of clinical interventions. The review was also used to inform the design and successful delivery of a randomised controlled trial of targeted screening and treatment. METHODS: Five databases (PubMed, CINHAL, SOCIOFILE, PsycINFO & Web of Science) were systematically searched, supplemented by reference tracking, searches of selected journals, and of relevant websites. We aimed to identify qualitative and quantitative studies that investigated knowledge of HBV and HCV among immigrants from high endemic areas to low endemic areas. Evidence, extracted according to a conceptual framework of Kleinman's explanatory model, was subjected to narrative synthesis. We adapted the PEN-3 model to categorise and analyse themes, and recommend strategies for interventions to influence help-seeking behaviour. RESULTS: We identified 51 publications including quantitative (n = 39), qualitative (n = 11), and mixed methods (n = 1) designs. Most of the quantitative studies included small samples and had heterogeneous methods and outcomes. The studies mainly concentrated on hepatitis B and ethnic groups of South East Asian immigrants residing in USA, Canada, and Australia. Many immigrants lacked adequate knowledge of aetiology, symptoms, transmission risk factors, prevention strategies, and treatment, of hepatitis HBV and HCV. Ethnicity, gender, better education, higher income, and English proficiency influenced variations in levels and forms of knowledge. CONCLUSION: Immigrants are vulnerable to HBV and HCV, and risk life-threatening complications from these infections because of poor knowledge and help-seeking behaviour. Primary studies in this area are extremely diverse and of variable quality precluding meta-analysis. Further research is needed outside North America and Australia

Revista de Revistas.

Psiquiatría dinámica en la "década del cerebro". Psychodynamic psychiatry in the "decade of the brain". G.o. Gabbard. Am J Pschiatry. Agosto 1992; 149: 991-998. J. Jáuregui Isasmendi El cambio psíquico: desarrollo en la teoría de las técnicas psicoanalíticas. Psychic change: development in the theory of psychoanalytic techniques. A. Cooper. International Journal of Psychoanalysis. Summer 1992; vol 73, part 2: pp 245-250. J. López Castillo ¿Tiene efecto catártico un intento de suicidio?. An attempted suicide actually have a cathartic effect?. Jo. Bronish. Acta Psychiatr Scand. 1992; 86: 228-232. M. Salvador Robert La exposición prenatal a la gripe no causa esquizofrenia. Prenatal exposure to influenza does not cause schizophrenia. JJ. Crovv, D.J. Oone. British Journal of Psychiatry. 1992; 161: 390-393. Rosa Villanueva Peña Alexitimia en mujeres con anorexia nerviosa. Alexithymia in women with anorexia nervosa. M.P Bourke et al. British Journal of Psychiatry. 1992; 161: 240-243. M. A. Casado Prieto Dinámica de caos en la actividad del sistema nervioso autónomo durante una sesión de psicoterapia. Chaotic dynamics in autonomic nervous system activity of a patient during a psychotherapy session. D.J. Redington, S.P Reidbord. Biol Psychiatry. 1992; 31: 984-992. P. Pérez Sales, T. Ferrer Gila Uso de psicofármacos en el paciente con infección por el virus de la inmunodeficiencia humana. J.L. Ayuso Mateas. Farmacología del S.N.C. Septiembre 1992; vol 6, N.o 3: pp 94-101. I. Morales Tratamiento de mantenimiento de la depresión recurrente orientación actual y futura. Maintenance treatment in recurrent depresion: current and future directions. D.J. Kupfer. British Journal 01 Psychiatry 1992; 161: 309-316. F. Rodríguez y González-Nicolás Comportamientos de riesgo para el VIH/SIDA entre los enfermos mentales crónicos. AIDS/HIV risk behavior among the cronic mentally ill. J.A. Kelly et al. Am J Psychiatry. July 1992; 149: 7. J.J. Marin Lozano Tipos de alcohólicos. 1. Evidencia de una tipología empírica basada en indicadores de vulnerabilidad y severidad. Types of alcoholics. l. Evidence for an empirically derived typology based on indicators of vulnerability and severity. TF Babor, M. Hofmann, FK. Del Broca, V Hesselbrock, R. E. Meyer, Z.S. Dolinsky, B. Rounsaville. Arch Gen Psychiatry. 1992; 49: 599-608. Pérez Jiménez, J.P. ¿Es el momento para una moratoria en la desinstitucionalización?. Is it time for a moratorium on deinstitutionalization?. R. Lamb. Hospital and Community Psychiatry. July 1992; vol 43, n.o 77. v. Aparicio Basauri Prevalencia de trastornos mentales en Subtiava, León, Nicaragua V Penayo, T Caldera, L. Jacobson Bol Of Sanit Panamá 1992; 113 (2). V. Aparicio Basauri ¿Cuánto tiempo debe continuarse un tratamiento de mantenimiento con neurolépticos?. How long should neuroleptic maintenance treatment continue?. W Kissling. Relapse. Issues in the Management of Chronic Psychosis. Vol 2, n.o 3. V. Aparicio Basauri El estado de la cuestión en... Consecuencias en pacientes adultos del abuso sexual en la infancia. A.E. Naf

Revista de Revistas.

Psiquiatría dinámica en la "década del cerebro". Psychodynamic psychiatry in the "decade of the brain". G.o. Gabbard. Am J Pschiatry. Agosto 1992; 149: 991-998. J. Jáuregui Isasmendi El cambio psíquico: desarrollo en la teoría de las técnicas psicoanalíticas. Psychic change: development in the theory of psychoanalytic techniques. A. Cooper. International Journal of Psychoanalysis. Summer 1992; vol 73, part 2: pp 245-250. J. López Castillo ¿Tiene efecto catártico un intento de suicidio?. An attempted suicide actually have a cathartic effect?. Jo. Bronish. Acta Psychiatr Scand. 1992; 86: 228-232. M. Salvador Robert La exposición prenatal a la gripe no causa esquizofrenia. Prenatal exposure to influenza does not cause schizophrenia. JJ. Crovv, D.J. Oone. British Journal of Psychiatry. 1992; 161: 390-393. Rosa Villanueva Peña Alexitimia en mujeres con anorexia nerviosa. Alexithymia in women with anorexia nervosa. M.P Bourke et al. British Journal of Psychiatry. 1992; 161: 240-243. M. A. Casado Prieto Dinámica de caos en la actividad del sistema nervioso autónomo durante una sesión de psicoterapia. Chaotic dynamics in autonomic nervous system activity of a patient during a psychotherapy session. D.J. Redington, S.P Reidbord. Biol Psychiatry. 1992; 31: 984-992. P. Pérez Sales, T. Ferrer Gila Uso de psicofármacos en el paciente con infección por el virus de la inmunodeficiencia humana. J.L. Ayuso Mateas. Farmacología del S.N.C. Septiembre 1992; vol 6, N.o 3: pp 94-101. I. Morales Tratamiento de mantenimiento de la depresión recurrente orientación actual y futura. Maintenance treatment in recurrent depresion: current and future directions. D.J. Kupfer. British Journal 01 Psychiatry 1992; 161: 309-316. F. Rodríguez y González-Nicolás Comportamientos de riesgo para el VIH/SIDA entre los enfermos mentales crónicos. AIDS/HIV risk behavior among the cronic mentally ill. J.A. Kelly et al. Am J Psychiatry. July 1992; 149: 7. J.J. Marin Lozano Tipos de alcohólicos. 1. Evidencia de una tipología empírica basada en indicadores de vulnerabilidad y severidad. Types of alcoholics. l. Evidence for an empirically derived typology based on indicators of vulnerability and severity. TF Babor, M. Hofmann, FK. Del Broca, V Hesselbrock, R. E. Meyer, Z.S. Dolinsky, B. Rounsaville. Arch Gen Psychiatry. 1992; 49: 599-608. Pérez Jiménez, J.P. ¿Es el momento para una moratoria en la desinstitucionalización?. Is it time for a moratorium on deinstitutionalization?. R. Lamb. Hospital and Community Psychiatry. July 1992; vol 43, n.o 77. v. Aparicio Basauri Prevalencia de trastornos mentales en Subtiava, León, Nicaragua V Penayo, T Caldera, L. Jacobson Bol Of Sanit Panamá 1992; 113 (2). V. Aparicio Basauri ¿Cuánto tiempo debe continuarse un tratamiento de mantenimiento con neurolépticos?. How long should neuroleptic maintenance treatment continue?. W Kissling. Relapse. Issues in the Management of Chronic Psychosis. Vol 2, n.o 3. V. Aparicio Basauri El estado de la cuestión en... Consecuencias en pacientes adultos del abuso sexual en la infancia. A.E. Naf