Programme de soins psychiatriques : Etude de l'expérience de jeunes patients par une méthode qualitative: Psychiatric care program: A qualitative study of the experience of young patients.

OBJECTIVE: Ambulatory care without consent is widely used, but it is controversial, and its effectiveness has not yet been proven. The patient experience remains largely unstudied in France, particularly that of young patients, yet their adherence to care in the early stages of the disease is complex and has an impact on their prognoses. The aim of this study is to investigate the experience of young patients undergoing a program of care (POC) in order to suggest ways of optimizing their care and to enrich the debate on the use of POCs. METHOD: Semi-structured interviews were conducted with 11 patients between ages 20 and 32, who were either undergoing a POC or had done so in the previous 5 years, followed by a semi-pragmatic phenomenological analysis of the resulting transcripts. RESULTS: (1) The outpatient experience with restraints is contradictory, ranging from deprivation and intrusion to support and protection. (2) The POC is portrayed as a framework for developing awareness of disorders and acceptance of care. (3) Patients report a lack of information about care with restraints, even to the point of being unaware of its existence. Patient-psychiatrist interactions within the POC are complicated by the restraints, but remain perceived as a care relationship. (4) They report constraints in their daily lives in connection to the POC, which can complicate professional involvement. CONCLUSION: The results support the importance of nurturing the therapeutic relationship within the POC and involving patients more in their care, starting with better information. They support the use of POCs as a temporary tool to be combined with work on adherence to treatment and support for social and professional reintegration. SPECIALTY: Psychiatry.

OBJECTIF: Les dispositifs de soins ambulatoires sans consentement sont largement utilisés, mais ils sont controversés et leur efficacité n'est pas prouvée à ce jour. L'expérience des patients concernés reste très peu étudiée en France, et notamment celui des jeunes patients, or leur adhésion aux soins en début de maladie est complexe et a un impact sur le pronostic futur. L'objectif est d'étudier l'expérience de jeunes patients suivis en programme de soins (PDS) afin de proposer des perspectives pour optimiser leur prise en charge et d'enrichir la réflexion sur l'utilisation des PDS. MÉTHODE: Des entretiens semi-directifs ont été réalisés auprès de 11 patients de 20 à 32 ans suivis en PDS ou l'ayant été dans les 5 dernières années, puis une analyse phénoménologique de type sémio-pragmatique a été réalisée sur les verbatims obtenus. RÉSULTATS: (1) L'expérience de la contrainte en ambulatoire est contrastée avec un vécu de privation de libertés et d'intrusion, mais aussi de soutien et de protection. (2) Le PDS est représenté comme un cadre permettant l'évolution de la conscience des troubles et de l'acceptation des soins. (3) Les patients rapportent un manque d'information sur les modalités de soins sous contrainte, pouvant aller jusqu'à la méconnaissance de l'existence de cette mesure. Les interactions patient-psychiatre au sein du PDS sont complexifiées par la contrainte mais restent perçues comme une relation de soin. (4) Ils rapportent des contraintes dans la vie quotidienne liées au PDS et qui peuvent compliquer l'insertion professionnelle. CONCLUSION: Les résultats soutiennent l'importance de soigner la relation thérapeutique au sein du PDS et d'impliquer davantage le patient dans sa prise en charge, en commençant par une meilleure information. Ils soutiennent une utilisation du PDS comme un outil temporaire à associer à un travail sur l'adhésion aux soins et à un accompagnement à la réinsertion sociale et professionnelle. SPÉCIALITÉ: Psychiatrie.

Deconvolution of BNP and NT-proBNP Immunoreactivities by Mass Spectrometry in Heart Failure and Sacubitril/Valsartan Treatment.

BACKGROUND: Elevated BNP and the N-terminal fragment of the proBNP (NT-proBNP) are hallmarks of heart failure (HF). Generally, both biomarkers parallel each other. In patients receiving sacubitril/valsartan, BNP remained stable while NT-proBNP decreased. As BNP and NT-proBNP assays have limited specificity due to cross-reactivity, we quantified by mass spectrometry (MS) the contributing molecular species. METHODS: We included 356 healthy volunteers, 100 patients with acute dyspnoea (49 acute decompensated HF; 51 dyspnoea of non-cardiac origin), and 73 patients with chronic HF and reduced ejection fraction treated with sacubitril/valsartan. BNP and NT-proBNP immunoreactivities (BNPir and NT-proBNPir) were measured by immunoassays (Abbott ARCHITECT and Roche Diagnostics proBNPII) and proBNP-derived peptides and glycosylation at serine 44 by MS on plasma samples. RESULTS: BNPir corresponded to the sum of proBNP1-108, BNP1-32, BNP3-32, and BNP5-32 (R2 = 0.9995), while NT-proBNPir corresponded to proBNP1-108 and NT-proBNP1-76 not glycosylated at serine 44 (R2 = 0.992). NT-proBNPir was better correlated (R2 = 0.9597) than BNPir (R2 = 0.7643) with proBNP signal peptide (a surrogate of proBNP production). In patients receiving sacubitril/valsartan, non-glycosylated NT-proBNP1-76 remained constant (P = 0.84) despite an increase in NT-proBNP1-76 and its glycosylation (P < 0.0001). ProBNP1-108 remained constant (P = 0.12) while its glycosylation increased (P < 0.0001), resulting in a decrease in non-glycosylated proBNP1-108 (P < 0.0001), and in NT-proBNPir. CONCLUSIONS: Glycosylation interfered with NT-proBNPir measurement, explaining the discrepant evolution of these 2 biomarkers in patients receiving sacubitril/valsartan. Both BNPir and NT-proBNPir are surrogates of proBNP1-108 production, NT-proBNPir being more robust in the clinical contexts studied.

Enhancing the precision limits of interferometric satellite geodesy missions.

Satellite geodesy uses the measurement of the motion of one or more satellites to infer precise information about the Earth's gravitational field. In this work, we consider the achievable precision limits on such measurements by examining approximate models for the three main noise sources in the measurement process of the current Gravitational Recovery and Climate Experiment (GRACE) Follow-On mission: laser phase noise, accelerometer noise and quantum noise. We show that, through time-delay interferometry, it is possible to remove the laser phase noise from the measurement, allowing for almost three orders of magnitude improvement in the signal-to-noise ratio. Several differential mass satellite formations are presented which can further enhance the signal-to-noise ratio through the removal of accelerometer noise. Finally, techniques from quantum optics have been studied, and found to have great promise for reducing quantum noise in other alternative mission configurations. We model the spectral noise performance using an intuitive 1D model and verify that our proposals have the potential to greatly enhance the performance of near-future satellite geodesy missions.

proANP Metabolism Provides New Insights Into Sacubitril/Valsartan Mode of Action.

BACKGROUND: Sacubitril/valsartan (S/V) treatment is beneficial in patients with heart failure with reduced ejection fraction (HFrEF), but its mode of action remains elusive, although it involves the increase in ANP (atrial natriuretic peptide). METHODS: Combining mass spectrometry and enzymatic assay in the plasma of 73 HFrEF patients treated with S/V and controls, we deciphered proANP processing that converts proANP into 4 vasoactive peptides. RESULTS: We found that proANP processing is sequential and involved meprin B, ECE (endothelin-converting enzyme) 1, and ANPEP (aminopeptidase N). This processing is limited in HFrEF patients via the downregulation of proANP production, corin, and meprin B activities by miR-425 and miR1-3p. S/V restored or compensated proANP processing by downregulating miR-425 and miR1-3p, hence increasing levels of proANP-derived bioactive peptides. In contrast, S/V directly and indirectly partially inhibited ECE1 and ANPEP. ECE1 partial inhibition resulted in a lower-than-expected increase in ET1 (endothelin 1), tilting the vasoactive balance toward vasodilation, and possibly hypotension. Furthermore, proANP glycosylation interferes with the midregional proANP assay -a clinical surrogate for proANP production, preventing any pathophysiological interpretation of the results. The analysis of S/V dose escalation with respect to baseline treatments suggests S/V-specific effects. CONCLUSIONS: These findings offer mechanistic evidence to the natriuretic peptide -defective state in HFrEF, which is improved by S/V. These data also strongly suggests that S/V increases plasma ANP by multiple mechanisms that involve 2 microRNAs, besides its protection from NEP (neprilysin) cleavage. Altogether, these data provide new insights on HFrEF pathophysiology and the mode of action of S/V.

Laser astrophysics experiment on the amplification of magnetic fields by shock-induced interfacial instabilities.

Laser experiments are becoming established as tools for astronomical research that complement observations and theoretical modeling. Localized strong magnetic fields have been observed at a shock front of supernova explosions. Experimental confirmation and identification of the physical mechanism for this observation are of great importance in understanding the evolution of the interstellar medium. However, it has been challenging to treat the interaction between hydrodynamic instabilities and an ambient magnetic field in the laboratory. Here, we developed an experimental platform to examine magnetized Richtmyer-Meshkov instability (RMI). The measured growth velocity was consistent with the linear theory, and the magnetic-field amplification was correlated with RMI growth. Our experiment validated the turbulent amplification of magnetic fields associated with the shock-induced interfacial instability in astrophysical conditions. Experimental elucidation of fundamental processes in magnetized plasmas is generally essential in various situations such as fusion plasmas and planetary sciences.

Acute Kidney Injury Induces Remote Cardiac Damage and Dysfunction Through the Galectin-3 Pathway.

Acute kidney injury is associated with increased risk of heart failure and mortality. This study demonstrates that acute kidney injury induces remote cardiac dysfunction, damage, injury, and fibrosis via a galectin-3 (Gal-3) dependent pathway. Gal-3 originates from bone marrow-derived immune cells. Cardiac damage could be prevented by blocking this pathway.

Continuous renal replacement therapy: understanding circuit hemodynamics to improve therapy adequacy.

PURPOSE OF REVIEW: The utilization of continuous renal replacement therapy (CRRT) increases throughout the world. Technological improvements have made its administration easier and safer. However, CRRT remains associated with numerous pitfalls and issues. RECENT FINDINGS: Even if new-generation CRRT devices have built-in safety features, understanding basic concepts remains of primary importance. SUMMARY: CRRT circuits' maximum recommended lifespan (72 h) can often not be achieved. Such early artificial kidney failures are typically related to two processes: circuit clotting and membrane clogging. Although these processes are to some degree inevitable, they are facilitated by poor therapy management. Indeed, the majority of device-triggered alarms are associated with blood pump interruption, which through blood stasis, enhance clotting and clogging. If the underlying issue is not adequately managed, further alarms will rapidly lead to prolonged stasis and complete circuit clotting or clogging making its replacement mandatory. Hence, rapid recognition of issues triggering alarms is of paramount importance. Because most alarms are related to circuit's hemodynamics, a thorough understanding of these concepts is mandatory for the staff in charge of delivering the therapy.This review describes CRRT circuits, measured and calculated pressures and the way their knowledge might improve therapy adequacy.

FTIR and UV spectroscopy studies of triplex formation between alpha-oligonucleotides with non-ionic phoshoramidate linkages and DNA targets.

The triplexes formed by pyrimidine alpha-oligodeoxynucleotides, 15mers alpha dT(15) or 12mers alpha dCT having dimethoxyethyl (PNHdiME), morpholino (PMOR) or propyl (PNHPr) non-ionic phosphoramidate linkages with DNA duplex targets have been investigated by UV and FTIR spectroscopy. Due to the decrease in the electrostatic repulsion between partner strands of identical lengths all modifications result in triplexes more stable than those formed with unmodified phosphodiester beta-oligodeoxynucleotides (beta-ODNs). Among the alpha-ODN third strands having C and T bases and non-ionic phosphoramidate linkages (alpha dCTPN) the most efficient modification is (PNHdiME). The enhanced third strand stability of the alpha dCTPN obtained as diastereoisomeric mixtures is attenuated by the steric hindrance of the PMOR linkages or by the hydrophobicity of the PNHPr linkages. All alpha dCTPN strands form triplexes even at neutral pH. In the most favorable case (PNHdiME), we show by FTIR spectroscopy that the triplex formed at pH 7 is held by Hoogsteen T*A.T triplets and in addition by an hydrogen bond between O6 of G and C of the third strand (Tm = 30 degrees C). The detection of protonated cytosines is correlated at pH 6 with a high stabilization of the triplex (Tm = 65 degrees C). While unfavorable steric effects are overcome with alpha anomers, the limitation of the pH dependence is not completely suppressed. Different triplexes are evidenced for non pH dependent phosphoramidate alpha-thymidilate strands (alpha dT(15)PN) interacting with a target duplex of identical length. At low ionic strength and DNA concentration we observe the binding to beta dA(15) either of alpha dT(15)PN as duplex strand and beta dT(15) as third strand, or of two hydrophobic alpha dT(15)PNHPr strands. An increase in the DNA and counterion concentration stabilizes the anionic target duplex and then the alpha dT(15)PN binds as Hoogsteen third strand.