Depression screening and management practices at a tertiary care cancer centre

Depression in cancer patients reduces patient survival and quality of life, though clinicians may not screen for depression, as part of routine practice. The current study examined depression screening and management behaviour at a tertiary care cancer centre by interviewing 10 oncologists and 10 nurses. The Theory of Planned Behaviour was applied to better understand screening behaviour. Results indicated clinicians screened for depression and managed depression by consulting other health professionals. This study found that depression is screened for and managed appropriately in patients, and certain components of the Theory of Planned Behaviour may be useful in understanding screening behaviour

Pratiques de dépistage et de prise en charge de la dépression dans un centre de cancérologie dispensant des soins tertiaires

Chez les patients atteints de cancer, la dépression réduit la survie et la qualité de vie, et pourtant, il se peut que les cliniciens ne cherchent pas à dépister la dépression dans le cadre de leur pratique courante. La présente étude a examiné les comportements en matière de dépistage et de prise en charge de la dépression dans un centre de cancérologie dispensant des soins tertiaires en effectuant des entrevues auprès de dix oncologues et de dix infirmières. La théorie du comportement planifié a été appliquée afin de mieux saisir les comportements en matière de dépistage. Les résultats indiquaient que les cliniciens effectuaient le dépistage de la dépression et qu’ils la prenaient en charge en consultant d’autres professionnels de la santé. Cette étude a permis de constater que la dépression fait l’objet d’un dépistage et d’une prise en charge appropriés chez les patients et que certains éléments de la théorie du comportement planifié pourraient améliorer la compréhension des comportements en matière de dépistage

Validation francophone de la grille d’évaluation de la douleur-déficience intellectuelle – version postopératoire

International audienc

Phospholipase A2 receptor 1 promotes lung cell senescence and emphysema in obstructive lung disease

International audienceBackground Cell senescence is a key process in age-associated dysfunction and diseases, notably chronic obstructive pulmonary disease (COPD). We previously identified phospholipase A2 receptor 1 (PLA2R1) as a positive regulator of cell senescence acting via Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling. Its role in pathology, however, remains unknown. Here, we assessed PLA2R1-induced senescence in COPD and lung emphysema pathogenesis. Methods We assessed cell senescence in lungs and cultured lung cells from patients with COPD and controls subjected to PLA2R1 knockdown, PLA2R1 gene transduction and treatment with the JAK1/2 inhibitor ruxolitinib. To assess whether PLA2R1 upregulation caused lung lesions, we developed transgenic mice overexpressing PLA2R1 ( PLA2R1 -TG) and intratracheally injected wild-type mice with a lentiviral vector carrying the Pla2r1 gene (LV- PLA2R1 mice). Results We found that PLA2R1 was overexpressed in various cell types exhibiting senescence characteristics in COPD lungs. PLA2R1 knockdown extended the population doubling capacity of these cells and inhibited their pro-inflammatory senescence-associated secretory phenotype (SASP). PLA2R1-mediated cell senescence in COPD was largely reversed by treatment with the potent JAK1/2 inhibitor ruxolitinib. Five-month-old PLA2R1 -TG mice exhibited lung cell senescence, and developed lung emphysema and lung fibrosis together with pulmonary hypertension. Treatment with ruxolitinib induced reversal of lung emphysema and fibrosis. LV- PLA2R1 -treated mice developed lung emphysema within 4 weeks and this was markedly attenuated by concomitant ruxolitinib treatment. Conclusions Our data support a major role for PLA2R1 activation in driving lung cell senescence and lung alterations in COPD. Targeting JAK1/2 may represent a promising therapeutic approach for COPD

Dysregulated Phenylalanine Catabolism Plays a Key Role in the Trajectory of Cardiac Aging

International audienceBackground: Aging myocardium undergoes progressive cardiac hypertrophy and interstitial fibrosis with diastolic and systolic dysfunction. Recent metabolomics studies shed light on amino acids in aging. The present study aimed to dissect how aging leads to elevated plasma levels of the essential amino acid phenylalanine and how it may promote age-related cardiac dysfunction. Methods: We studied cardiac structure and function, together with phenylalanine catabolism in wild-type (WT) and p21 −/− mice (male; 2–24 months), with the latter known to be protected from cellular senescence. To explore phenylalanine’s effects on cellular senescence and ectopic phenylalanine catabolism, we treated cardiomyocytes (primary adult rat or human AC-16) with phenylalanine. To establish a role for phenylalanine in driving cardiac aging, WT male mice were treated twice a day with phenylalanine (200 mg/kg) for a month. We also treated aged WT mice with tetrahydrobiopterin (10 mg/kg), the essential cofactor for the phenylalanine-degrading enzyme PAH (phenylalanine hydroxylase), or restricted dietary phenylalanine intake. The impact of senescence on hepatic phenylalanine catabolism was explored in vitro in AML12 hepatocytes treated with Nutlin3a (a p53 activator), with or without p21-targeting small interfering RNA or tetrahydrobiopterin, with quantification of PAH and tyrosine levels. Results: Natural aging is associated with a progressive increase in plasma phenylalanine levels concomitant with cardiac dysfunction, whereas p21 deletion delayed these changes. Phenylalanine treatment induced premature cardiac deterioration in young WT mice, strikingly akin to that occurring with aging, while triggering cellular senescence, redox, and epigenetic changes. Pharmacological restoration of phenylalanine catabolism with tetrahydrobiopterin administration or dietary phenylalanine restriction abrogated the rise in plasma phenylalanine and reversed cardiac senescent alterations in aged WT mice. Observations from aged mice and human samples implicated age-related decline in hepatic phenylalanine catabolism as a key driver of elevated plasma phenylalanine levels and showed increased myocardial PAH-mediated phenylalanine catabolism, a novel signature of cardiac aging. Conclusions: Our findings establish a pathogenic role for increased phenylalanine levels in cardiac aging, linking plasma phenylalanine levels to cardiac senescence via dysregulated phenylalanine catabolism along a hepatic-cardiac axis. They highlight phenylalanine/PAH modulation as a potential therapeutic strategy for age-associated cardiac impairment

Dysregulated Phenylalanine Catabolism Plays a Key Role in the Trajectory of Cardiac Aging

International audienceBackground: Aging myocardium undergoes progressive cardiac hypertrophy and interstitial fibrosis with diastolic and systolic dysfunction. Recent metabolomics studies shed light on amino acids in aging. The present study aimed to dissect how aging leads to elevated plasma levels of the essential amino acid phenylalanine and how it may promote age-related cardiac dysfunction. Methods: We studied cardiac structure and function, together with phenylalanine catabolism in wild-type (WT) and p21 −/− mice (male; 2–24 months), with the latter known to be protected from cellular senescence. To explore phenylalanine’s effects on cellular senescence and ectopic phenylalanine catabolism, we treated cardiomyocytes (primary adult rat or human AC-16) with phenylalanine. To establish a role for phenylalanine in driving cardiac aging, WT male mice were treated twice a day with phenylalanine (200 mg/kg) for a month. We also treated aged WT mice with tetrahydrobiopterin (10 mg/kg), the essential cofactor for the phenylalanine-degrading enzyme PAH (phenylalanine hydroxylase), or restricted dietary phenylalanine intake. The impact of senescence on hepatic phenylalanine catabolism was explored in vitro in AML12 hepatocytes treated with Nutlin3a (a p53 activator), with or without p21-targeting small interfering RNA or tetrahydrobiopterin, with quantification of PAH and tyrosine levels. Results: Natural aging is associated with a progressive increase in plasma phenylalanine levels concomitant with cardiac dysfunction, whereas p21 deletion delayed these changes. Phenylalanine treatment induced premature cardiac deterioration in young WT mice, strikingly akin to that occurring with aging, while triggering cellular senescence, redox, and epigenetic changes. Pharmacological restoration of phenylalanine catabolism with tetrahydrobiopterin administration or dietary phenylalanine restriction abrogated the rise in plasma phenylalanine and reversed cardiac senescent alterations in aged WT mice. Observations from aged mice and human samples implicated age-related decline in hepatic phenylalanine catabolism as a key driver of elevated plasma phenylalanine levels and showed increased myocardial PAH-mediated phenylalanine catabolism, a novel signature of cardiac aging. Conclusions: Our findings establish a pathogenic role for increased phenylalanine levels in cardiac aging, linking plasma phenylalanine levels to cardiac senescence via dysregulated phenylalanine catabolism along a hepatic-cardiac axis. They highlight phenylalanine/PAH modulation as a potential therapeutic strategy for age-associated cardiac impairment