RESUMEN
In the context of widespread loss, isolation, and grief due to COVID-19, palliative social workers came together in the fall of 2020 to form an international group named the World Hospice and Palliative Care Social Work Network (WHPCSW). This emerging global network is committed to amplifying the innovative work, nuanced skills, research, and education and training provided by palliative social workers across different settings around the world. This article highlights some of the novel interventions developed by social workers in response to the pandemic and describes this coalescing WHPCSW network along with information about its mission and membership.
Asunto(s)
COVID-19/terapia , Cuidados Paliativos/métodos , Calidad de Vida/psicología , Trabajadores Sociales/educación , Actitud Frente a la Muerte , COVID-19/psicología , Humanos , Cuidados Paliativos/psicología , Servicio Social , Trabajadores Sociales/psicologíaRESUMEN
Background: In literature there is a lack of specific evaluation tools for behavior in intellectual disabilities in general and during an activity, this is one of the most important field of the Occupational Therapy intervention. Objective: Authors developed an Italian version of the Occupational Therapy Task Observation Scale (OTTOS) and an Italian version of the Comprehensive Occupational Therapy Evaluation Scale (COTES) and examined their reliability and validity. Methods: The original scales were translated from English to Italian using the "Translation and Cultural Adaptation of Patient Reported Outcomes Measures-Principles of Good Practice" guidelines. Both scales were administered to adults with mild and moderate intellectual disabilities. People under eighteen years, with severe and profound intellectual disabilities and deaf people were excluded from the study. Their reliability and validity have been examined. Relia-bility was analyzed via internal consistency (Cronbach's alpha) and stability (intra/inter-rater coefficient), while validity was investigated via construct validity (p-value) and criterion validity using Pearson's correlation coefficients between them and with the Mini Mental State Examination and the Barthel Index Scale. Results: The OTTOS and the COTES were administered to 30 subjects. Cronbach's α for the COTES was 0,91 and Cronbach's α for the OTTOS was 0,92. Regarding the criterion of validity, the two scales have numerous statistically positive correlations, particularly with the Mini Mental State Examination in the Orientation and total part. Furthermore, the correlation with the Barthel scale is present in the total scores, the COTES's third subscale, and the OTTOS's first. Conclusions: The OTTOS and the COTES were reliable and valid outcome measures for assessing behavior in the Italian population.
Asunto(s)
Discapacidad Intelectual , Terapia Ocupacional , Adulto , Humanos , Reproducibilidad de los Resultados , Psicometría , Italia , Encuestas y CuestionariosRESUMEN
Evidence indicates that lipoxygenases (LO) may play a role in cancer cell survival. We show that human malignant pleural mesothelial (MM) cells, but not normal mesothelial (NM) cells, express a catalytically active 5-LO. Pharmacological or genetic inhibition of MM cell 5-LO determined nucleosome formation and induced a DNA fragmentation pattern typical of apoptosis. This was completely reversed by exogenously added 5(S)-HETE but not by 12(S)-, 15(S)-HETE, or leukotriene (LT)B4. A 5-LO antisense oligonucleotide potently and time-dependently reduced vascular endothelial growth factor (VEGF) mRNA and constitutive VEGF accumulation in the conditioned media of MM cells. When NM cells were transfected with a 5-LO cDNA, basal and arachidonic acid-induced VEGF formation increased consistently by 6- and 12-fold, respectively. This was associated with a significant increase in DNA synthesis that was counteracted by a specific anti-VEGF antibody. Arachidonic acid and 5(S)-HETE also potently stimulated the activity of a VEGF promoter construct. Thus, 5-LO is a key regulator of MM cell proliferation and survival via a VEGF-related circuit.
Asunto(s)
Araquidonato 5-Lipooxigenasa/metabolismo , Supervivencia Celular/fisiología , Mesotelioma/patología , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Araquidonato 5-Lipooxigenasa/genética , Ácido Araquidónico/farmacología , Benzoquinonas/farmacología , División Celular/efectos de los fármacos , División Celular/fisiología , Línea Celular , Supervivencia Celular/efectos de los fármacos , ADN sin Sentido/genética , ADN sin Sentido/farmacología , Factores de Crecimiento Endotelial/genética , Factores de Crecimiento Endotelial/metabolismo , Regulación de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Proteínas Fluorescentes Verdes , Humanos , Inhibidores de la Lipooxigenasa/farmacología , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Linfocinas/efectos de los fármacos , Linfocinas/genética , Linfocinas/metabolismo , Masoprocol/farmacología , Mesotelioma/enzimología , Mutación , Regiones Promotoras Genéticas/genética , ARN/efectos de los fármacos , ARN/genética , ARN/metabolismo , Proteínas Recombinantes de Fusión/efectos de los fármacos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Timidina/metabolismo , Factores de Tiempo , Transcripción Genética , Transfección , Tritio , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
In this study, we investigated the regulation of different G protein-coupled receptor (GPCR)-stimulated signaling pathways by GPCR kinase 2 (GRK2). We used thyrotropin receptor, which is coupled to different G proteins, to investigate the regulation of Galphas- and Galphaq-mediated signaling (assessed by cAMP and inositol phosphate production, respectively). In transfected cells, both pathways were desensitized by GRK2. However a kinase-dead GRK2 mutant (GRK2-K220R) only decreased inositol phosphate production, indicating that GRK2 could regulate Galphaq signaling through a phosphorylation-independent mechanism. Similar results were obtained with serotonin receptor 5-hydroxytryptamine(2C), which is coupled to Galphaq. This effect was mimicked by the N-terminal domain of GRK2 (GRK2-Nter), but not by the C-terminal domain. In cells transfected with Galphaq, direct activation of Galphaq signaling (by AlF(4)(-)) was desensitized by GRK2-Nter, indicating an effect at the Galpha-level. For comparison, in parallel samples we studied a protein regulator of G protein signaling RGS4 and we found a similar regulatory profile. We therefore hypothesized that the GRK2-Nter could directly interact with the Galphaq subunit to regulate its signaling, as demonstrated for several RGS proteins. This hypothesis is further supported by the presence, within the GRK2-Nter, of an RGS homology domain. In direct binding experiments, we found that GRK2-Nter interacts with Galphaq (only when activated) but not with Galphas and Galphao. We conclude that GRK2, besides desensitizing the GPCR by phosphorylation, is able to selectively bind to Galphaq and to regulate its signaling.
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Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Reguladores de Proteínas de Unión al GTP/metabolismo , Proteínas de Unión al GTP/metabolismo , Animales , Células COS , Células Cultivadas , Proteínas Quinasas Dependientes de AMP Cíclico/química , Subunidades alfa de la Proteína de Unión al GTP Gq-G11 , Humanos , Fosforilación , Conformación Proteica , Receptores de Superficie Celular/metabolismo , Transducción de Señal , Quinasas de Receptores Adrenérgicos betaRESUMEN
G-protein-coupled receptor kinases (GRKs) are involved in the regulation of many G-protein-coupled receptors. As opposed to the other GRKs, such as rhodopsin kinase (GRK1) or beta-adrenergic receptor kinase (beta ARK, GRK2), no receptor substrate for GRK4 has been so far identified. Here we show that GRK4 is expressed in cerebellar Purkinje cells, where it regulates mGlu(1) metabotropic glutamate receptors, as indicated by the following: 1) When coexpressed in heterologous cells (HEK293), mGlu(1) receptor signaling was desensitized by GRK4 in an agonist-dependent manner (homologous desensitization). 2) In transfected HEK293 and in cultured Purkinje cells, the exposure to glutamate agonists induced internalization of the receptor and redistribution of GRK4. There was a substantial colocalization of the receptor and kinase both under basal condition and after internalization. 3) Kinase activity was necessary for desensitizing mGlu(1a) receptor and agonist-dependent phosphorylation of this receptor was also documented. 4) Antisense treatment of cultured Purkinje cells, which significantly reduced the levels of GRK4 expression, induced a marked modification of the mGlu(1)-mediated functional response, consistent with an impaired receptor desensitization. The critical role for GRK4 in regulating mGlu(1) receptors implicates a major involvement of this kinase in the physiology of Purkinje cell and in motor learning.