ICD-11 and DSM-5-TR prolonged grief symptoms and quality of life: A criterion validity test.

OBJECTIVE: Two similar but distinct versions of prolonged grief disorder (PGD) have recently been included in the International Classification of Diseases eleventh edition (ICD-11) and the Diagnostic and Statistical Manual of Mental Disorders - fifth edition, Text-Revision (DSM-5-TR). This study provides a criterion validity test of both new criteria sets of PGD, by examining concurrent and longitudinal associations of ICD-11 and DSM-5-TR prolonged grief symptoms with quality of life (QOL). METHODS: Bereaved adults completed a survey assessing ICD-11 and DSM-5-TR prolonged grief symptoms, depressive symptoms, insomnia symptoms and QOL at baseline and 6-month follow-up. RESULTS: Both ICD-11 and DSM-5-TR prolonged grief symptoms related negatively to QOL concurrently, while controlling for insomnia and depressive symptoms. ICD-11 prolonged grief symptoms, but not DSM-5-TR prolonged grief symptoms, predicted QOL at 6-month follow-up, while controlling for baseline QOL and insomnia and depression symptoms. CONCLUSIONS: Results provide consistent evidence for the criterion validity of ICD-11 PGD, but mixed evidence for the criterion validity of DSM-5-TR PGD. Study results can help guide attempts to optimize and harmonize future PGD criteria.

Cumulative growth and stress responses to the 2018-2019 drought in a European floodplain forest.

Droughts increasingly threaten the world's forests and their potential to mitigate climate change. In 2018-2019, Central European forests were hit by two consecutive hotter drought years, an unprecedented phenomenon that is likely to occur more frequently with climate change. Here, we examine tree growth and physiological stress responses (increase in carbon isotope composition; Δδ13 C) to this consecutive drought based on tree rings of dominant tree species in a Central European floodplain forest. Tree growth was not reduced for most species in 2018, indicating that water supply in floodplain forests can partly buffer meteorological water deficits. Drought stress responses in 2018 were comparable to former single drought years but the hotter drought in 2018 induced drought legacies in tree growth while former droughts did not. We observed strong decreases in tree growth and increases in Δδ13 C across all tree species in 2019, which are likely driven by the cumulative stress both consecutive hotter droughts exerted. Our results show that consecutive hotter droughts pose a novel threat to forests under climate change, even in forest ecosystems with comparably high levels of water supply.

Exploring the Correlation and Protective Role of Diabetes Mellitus in Aortic Aneurysm Disease.

Introduction: Diabetes mellitus is recognised as a significant risk factor for cardiovascular and peripheral vascular disease, as the abnormal metabolic state increases the risk for atherosclerosis, occlusive arterial disease and vascular dysfunction. There have been reports of potential association across the literature that illustrates a link between diabetes mellitus and aortic aneurysm, with the former having a protective role on the development of the latter. Methods: A thorough literature search was performed through electronic databases, to provide a comprehensive review of the study's reporting on the association of diabetes mellitus and aortic aneurysm, discussing the mechanisms that have been reported; furthemore, we reviewed the reports of the impact of oral hypoglycameic agents on aortic aneurysms. Results: Various proposed mechanisms are involved in this protective process including endothelial dysfunction, chronic hyperglycemia and insulin resistance. The evidence suggests a negative association between these disease process, with prevelance of diabetes mellitus resulting in lower rates of aortic aneurysm, via its protective mechanistic action. The increase in advanced glycation end products, increased arterial stiffness and vascular remodelling seen in diabetes, was found to have a profound impact on aneurysm development, its slow progression and lower rupture rate in these individuals. This review has also highlighted the role of oral hypoglycaemic agents having a protective effect against AA disease. Conclusion: A decrease in development, progression and mortality from aortic aneurysms as well as reduced rates of dissection, have been observed in those with diabetes. This review has provided a comprehensive insight on the effect of diabetes and its physiological processes, and elements of its con-committant treatment, having a protective role against these aortic diseases.

A Severe Case of Anaplastic Large Cell Lymphoma in a Previously Healthy Woman: Diagnostic and Therapeutic Challenges.

Anaplastic large cell lymphomas are an aggressive subtype of peripheral T-cell lymphomas that can manifest with a variety of symptoms. Our case highlights the importance of prompt tissue sampling, especially if an associated hemophagocytic lymphohistiocytosis is detected and no clinical improvement is observed upon glucocorticoid treatment.

cMyc and ERK activity are associated with resistance to ALK inhibitory treatment in glioblastoma.

BACKGROUND: Anaplastic lymphoma kinase (ALK) is expressed in ~ 60% of glioblastomas and conveys tumorigenic functions. Therefore, ALK inhibitory strategies with alectinib are conceivable for patients with glioblastoma. The aims of this preclinical study were to investigate efficacy as well as to understand and potentially overcome primary and acquired resistance mechanisms of alectinib in glioblastoma. METHODS: Efficacy of alectinib was analyzed dependent on ALK expression in different glioblastoma initiating cells and after lentiviral knockdown of ALK. Alectinib resistant cells were generated by continuous treatment with increasing alectinib doses over 3 months. M-RNA, phospho-protein and protein regulation were analyzed to decipher relevant pathways associated to treatment or resistance and specifically inhibited to evaluate rational salvage therapies. RESULTS: Alectinib reduced clonogenicity and proliferation and induced apoptosis in ALK expressing glioblastoma initiating cells, whereas cells without ALK expression or after ALK depletion via knockdown showed primary resistance against alectinib. High expression of cMyc and activation of the ERK1/2 pathway conferred resistance against alectinib in ALK expressing glioblastoma cells. Pharmacological inhibition of these pathways by cMyc inhibitor or MEK inhibitor, trametinib, overcame alectinib resistance and re-sensitized resistant cells to continued alectinib treatment. The combination of alectinib with radiotherapy demonstrated synergistic effects in inhibition of clonogenicity in non-resistant and alectinib resistant glioblastoma cells. CONCLUSION: The data offer rationales for alectinib treatment in ALK expressing glioblastoma and for the use of ALK expression status as potential biomarker for alectinib treatment. In addition, the results propose MEK inhibition or radiotherapy as reasonable salvage treatments after acquired alectinib resistance.

Targeting Resistance against the MDM2 Inhibitor RG7388 in Glioblastoma Cells by the MEK Inhibitor Trametinib.

PURPOSE: Resistance is an obstacle of glioma therapy. Despite targeted interventions, tumors harbor primary resistance or become resistant over short course of treatment. This study examined the mouse double minute 2 (MDM2) inhibitor RG7388 together with radiotherapy and analyzed strategies to overcome acquired MDM2 inhibitor resistance in glioblastoma. EXPERIMENTAL DESIGN: Effects of RG7388 and radiotherapy were analyzed in p53 wild-type glioblastoma cell lines and glioma-initiating cells. RG7388 resistant cells were generated by increasing RG7388 doses over 3 months. Regulated pathways were investigated by microarray, qRT-PCR, and immunoblot analysis and specifically inhibited to evaluate rational salvage therapies at RG7388 resistance. Effects of RG7388 and trametinib treatment were challenged in an orthotopical mouse model with RG7388 resistant U87MG glioblastoma cells. RESULTS: MDM2 inhibition required functional p53 and showed synergistic activity with radiotherapy in first-line treatment. Long-term exposure to RG7388 induced resistance by activation of the extracellular signal-regulated kinases 1/2 (ERK1/2)-insulin growth factor binding protein 1 (IGFBP1) signaling cascade, which was specifically overcome by ERK1/2 pathway inhibition with trametinib and knockdown of IGFBP1. Combining trametinib with continued RG7388 treatment enhanced antitumor effects at RG7388 resistance in vitro and in vivo. CONCLUSIONS: These data provide a rationale for combining RG7388 and radiotherapy as first-line therapy with a specific relevance for tumors insensitive to alkylating standard chemotherapy and for the addition of trametinib to continued RG7388 treatment as salvage therapy after acquired resistance against RG7388 for clinical practice.

Perversão e contemporaneidade: um discurso equivocado? / Perversión y contemporaneidad: un discurso equivocado? / Perversion and contemporaneity: a mistaken discourse?

Este trabalho teve como objetivo examinar a produção psicanalítica sobre a perversão nas últimas décadas, tendo como recorte as relações que os autores fazem entre perversão e contemporaneidade. Para a execução da pesquisa, tivemos como fonte artigos psicanalíticos indexados pela American Psychology Association (PsycInfo/APA), artigos de revistas psicanalíticas e capítulos de livros cujo tema é a perversão, mas no ponto em que esta faz uma interseção com a contemporaneidade. Para análise do material encontrado, categorias temáticas foram criadas: "perversão e patologias atuais", "laços sociais perversos" e "perversionalização ou obsessionalização?". Com esta pesquisa, percebemos que a perversão é um tema frequente no discurso atual da psicanálise; no entanto, muitas vezes esse vocábulo e seu derivado, "perverso", são empregados indiscriminadamente para denunciar tudo o que é imoral e mau na sociedade. Diante disso, corre‑se o risco da banalização da perversão, fugindo esta do seu sentido psicanalítico.(AU)

The aim of this study was to examine the psychoanalytic production on perversion in the last decades, focusing on the relations the authors establish between perversion and contemporaneity. To carry out this research, we consulted psychoanalytic papers indexed by the American Psychology Association (PsycInfo/APA), papers of psychoanalytic journals, and chapters of books whose topic is perversion, but at its intersection with contemporaneity. To analyse the material found, thematic categories were created: "perversion and current pathologies", "perverse social bonds", and "perversionization or obsessionization?". Through this research, we realized that perversion is a very frequent topic in the current psychoanalysis discourse; however, often this term and its derivative, "perverse", are used indiscriminately to denounce everything that is immoral and evil in the society. This way, there is a risk of trivializing perversion, escaping from its original psychoanalytic sense.(AU)

El objetivo deste estudio fue analizar la producción de la psicoanálisis sobre la perversión en las últimas décadas, centrandose en las relaciones que los autores hacen acerca de la perversión e de la contemporaneidad. Para la realización de esta investigación utilizamos artículos psicoanalíticos indexados en la Asociación Americana de Psicología (PsycInfo/APA), artículos de publicaciones psicoanalíticas y capítulos de libros cuyo tema es la perversión, y sobre todo sus intersecciones con la contemporaneidad. Para el análisis del material encontrado, creamos categorias temáticas: "perversión y patologías actuales", "lazos sociales perversos", y "perversionización o obsesionización?". Con esta investigación, comprendimos que la perversión es una temática frecuente en el discurso actual de la psicoanálisis; no obstante, muchas veces esa palabra y su derivado, "perverso", son utilizados para denunciar todo lo que es inmoral y mal en la sociedad. Teniendo en cuenta esto, se corre el riesgo de trivializar la perversión, huyendo de su sentido psicoanalítico.(AU)

Perversão e contemporaneidade: um discurso equivocado? / Perversion and contemporaneity: a mistaken discourse? / Perversión y contemporaneidad: un discurso equivocado?

Este trabalho teve como objetivo examinar a produção psicanalítica sobre a perversão nas últimas décadas, tendo como recorte as relações que os autores fazem entre perversão e contemporaneidade. Para a execução da pesquisa, tivemos como fonte artigos psicanalíticos indexados pela American Psychology Association (PsycInfo/APA), artigos de revistas psicanalíticas e capítulos de livros cujo tema é a perversão, mas no ponto em que esta faz uma interseção com a contemporaneidade. Para análise do material encontrado, categorias temáticas foram criadas: "perversão e patologias atuais", "laços sociais perversos" e "perversionalização ou obsessionalização?". Com esta pesquisa, percebemos que a perversão é um tema frequente no discurso atual da psicanálise; no entanto, muitas vezes esse vocábulo e seu derivado, "perverso", são empregados indiscriminadamente para denunciar tudo o que é imoral e mau na sociedade. Diante disso, corre‑se o risco da banalização da perversão, fugindo esta do seu sentido psicanalítico.

The aim of this study was to examine the psychoanalytic production on perversion in the last decades, focusing on the relations the authors establish between perversion and contemporaneity. To carry out this research, we consulted psychoanalytic papers indexed by the American Psychology Association (PsycInfo/APA), papers of psychoanalytic journals, and chapters of books whose topic is perversion, but at its intersection with contemporaneity. To analyse the material found, thematic categories were created: "perversion and current pathologies", "perverse social bonds", and "perversionization or obsessionization?". Through this research, we realized that perversion is a very frequent topic in the current psychoanalysis discourse; however, often this term and its derivative, "perverse", are used indiscriminately to denounce everything that is immoral and evil in the society. This way, there is a risk of trivializing perversion, escaping from its original psychoanalytic sense.

El objetivo deste estudio fue analizar la producción de la psicoanálisis sobre la perversión en las últimas décadas, centrandose en las relaciones que los autores hacen acerca de la perversión e de la contemporaneidad. Para la realización de esta investigación utilizamos artículos psicoanalíticos indexados en la Asociación Americana de Psicología (PsycInfo/APA), artículos de publicaciones psicoanalíticas y capítulos de libros cuyo tema es la perversión, y sobre todo sus intersecciones con la contemporaneidad. Para el análisis del material encontrado, creamos categorias temáticas: "perversión y patologías actuales", "lazos sociales perversos", y "perversionización o obsesionización?". Con esta investigación, comprendimos que la perversión es una temática frecuente en el discurso actual de la psicoanálisis; no obstante, muchas veces esa palabra y su derivado, "perverso", son utilizados para denunciar todo lo que es inmoral y mal en la sociedad. Teniendo en cuenta esto, se corre el riesgo de trivializar la perversión, huyendo de su sentido psicoanalítico.