Introducing a Smart Toy in Eating Disorder Treatment: A Pilot Study.

Individuals with eating disorders (EDs) often encounter challenges related to body image, emotional, and sensory difficulties during nutritional rehabilitation. To address these challenges, a novel technology-enabled smart toy, Purrble, designed for immediate assistance in emotion regulation, is being explored. A mixed-method approach involving workshops, diaries, and focus groups was employed to examine the feasibility of Purrble as a therapeutic tool and its impact on participants' daily routines, sensory experiences, and emotional states. The study results demonstrate the engagement and acceptability of this device. Qualitative analysis revealed that participants independently used and integrated Purrble into their emotional and sensory regulation practices. These pilot results support the potential for a shift in the delivery of adjunct therapeutic tools through technology, particularly for ED patients with complex presentations. Future research is necessary to further explore the psychological benefits of this intervention.

Routine surgeries during the COVID-19 pandemic: A French nationwide cohort study.

Background: The COVID-19 pandemic inevitably had consequences on routine surgical procedures. The objective was to quantify changes to five surgical procedures during the COVID-19 pandemic namely cataract surgery, hip and knee arthoplasties, coronary revascularization by angioplasty and definitive cardiac stimulation. Materials and method: All hospitalizations with at least one act of each surgery between January 1, 2019, and June 30, 2021, were included from the database of all French residents' health-related expenses. Percentage changes between observed and expected numbers of hospital stays were calculated for each surgery in 2020 and the first half of 2021 with 95% Confidence Intervals. Expected numbers were calculated from the number in 2019 by applying an average annual change between 2015 and 2019. The type of intervention (primary operation or reoperation/revision) and/or the emergency status were also considered. Results: A total of 2,153,857 hospitalizations for cataract surgery (0.6% revision), 398,213 for hip arthroplasty (10.9% revision and 26.9% in emergency), 276,607 for knee arthroplasty (8.2% revision), 471,318 for coronary angioplasty (48.7% in emergency) and 178,441 for cardiac stimulation (27.6% revision) were included. Activity was lower than expected in 2020 (cataract surgery: -21.9% [-22.5;-21.4]; hip arthroplasty: -13.4% [-14.8;-12.0]; knee arthroplasty: -24.6% [-26.1;-23.0]; coronary angioplasty: -11.2% [-12.7;-9.7]) without any catch-up in the first half of 2021 (cataract surgery: -5.0% [-5.8;-4.3]; hip arthroplasty: -9.9% [-11.6;-8.2]; knee arthroplasty: -22.0% [-24.0;-20.1]; coronary angioplasty: -12,1% [-13.9;-10.4]). Revisions and non-elective interventions also decreased but to a lesser magnitude. Cardiac stimulation activity was almost in line with expectations (-2.6% [-4.9; -0.3]/+0.6 [-2.2; +3.4]). Conclusion: This study shows that there was a marked decrease in four routine surgeries compared to expectations through to at least the first half of 2021, despite the gradual national rollout of the vaccine.

Major ischaemic and bleeding risks following current drug-eluting stent implantation: Are there differences across current drug-eluting stent types in real life?

BACKGROUND: Current drug-eluting stents (c-DESs) reduce the occurrence of ischaemic events, but expose recipients to stent thrombosis and bleeding secondary to preventive antiplatelet therapy. To date, comparative data on the relative effectiveness and safety of the various c-DESs in real life are limited. AIM: To compare ischaemic and bleeding risks across the major c-DESs used in France. METHODS: French national health insurance reimbursement and hospitalization databases were used. Patients implanted with a c-DES in 2014 were followed for 1 year. The risks of ischaemic events (revascularization, myocardial infarction and/or stroke), major bleeding events and death were compared across six c-DESs (XIENCE®, PROMUS®, RESOLUTE®, BIOMATRIX®, NOBORI® and ORSIRO®), using multilevel Cox models adjusted for baseline individual and hospital characteristics. RESULTS: A total of 52,891 subjects were included: 34.4% with XIENCE®; 27.6% with PROMUS®; 24.0% with RESOLUTE®; 8.0% with BIOMATRIX®; 5.0% with NOBORI®; and 1.0% with ORSIRO®. Among them, 9378 had at least one event (ischaemic, 6064; major bleeding, 1968; death, 2411), resulting in an overall incidence rate of 19 per 100 person-years. In the multivariable analysis, the risk of ischaemic events, major bleeding events or death did not differ between the c-DESs overall (adjusted hazard ratios between 0.85 [95% confidence interval 0.68-1.07] and 1.04 [95% confidence interval 0.98-1.10] compared with XIENCE® used as the reference) and when each outcome was considered separately. CONCLUSIONS: In real life, major ischaemic and bleeding risks do not differ across the various c-DESs over the first year following implantation. Future studies are needed to assess comparative c-DES effectiveness and safety longer term.

Erythrocytes encapsulated with phenylalanine hydroxylase exhibit improved pharmacokinetics and lowered plasma phenylalanine levels in normal mice.

Enzyme replacement therapy is often hampered by the rapid clearance and degradation of the administered enzyme, limiting its efficacy and requiring frequent dosing. Encapsulation of therapeutic molecules into red blood cells (RBCs) is a clinically proven approach to improve the pharmacokinetics and efficacy of biologics and small molecule drugs. Here we evaluated the ability of RBCs encapsulated with phenylalanine hydroxylase (PAH) to metabolize phenylalanine (Phe) from the blood and confer sustained enzymatic activity in the circulation. Significant quantities of PAH were successfully encapsulated within murine RBCs (PAH-RBCs) with minimal loss of endogenous hemoglobin. While intravenously administered free PAH enzyme was rapidly eliminated from the blood within a few hours, PAH-RBCs persisted in the circulation for at least 10days. A single injection of PAH-RBCs was able to decrease Phe levels by nearly 80% in normal mice. These results demonstrate the ability of enzyme-loaded RBCs to metabolize circulating amino acids and highlight the potential to treat disorders of amino acid metabolism.

Pancreatic tumor sensitivity to plasma L-asparagine starvation.

OBJECTIVES: In this study, our aim was to test whether asparagine synthetase (ASNS) deficiency in pancreatic malignant cells can lead to sensitivity to asparagine starvation. We also investigated, in tumor-bearing mice, the efficacy of L-asparaginase entrapped in red blood cells (RBCs), a safe formulation, to induce asparagine depletion. METHODS: First, ASNS expression was evaluated by immunohistochemistry in sporadic pancreatic ductal adenocarcinoma. Then, 4 pancreatic carcinoma cell lines were examined by Western blot, immunocytochemistry, and cytotoxicity assay to L-asparaginase and in asparagine-free or reduced-asparagine media. Finally, mice bearing the most in vitro sensitive cell line received RBC-entrapped L-asparaginase to investigate the anticancer efficacy of serum asparagine depletion in vivo. RESULTS: Approximately 52% of pancreatic adenocarcinomas expressed no or low ASNS. The highest in vitro cytotoxicity to L-asparaginase or to reduced asparagine medium was observed with SW1990 line when ASNS expression was the lowest. In vivo sensitivity was confirmed for this cell line. CONCLUSIONS: Plasma asparagine depletion by RBC-entrapped L-asparaginase in selected patients having no low or no ASNS may be a promising therapeutic approach for pancreatic cancer.

Drug-eluting stents in patients at high risk of restenosis: assessment for France.

BACKGROUND: In unselected patients, the incidence of restenosis is lower after placement of drug-eluting stents (DES) than bare-metal stents (BMS) without difference in safety at a time horizon of 4 years. However, DES appears less effective in "off label" patients. OBJECTIVES: The aim of the study was to assess available evidence of DES efficacy and safety by patient category to establish when DES placement may be recommended for reimbursement by the French national health insurance. METHODS: Based on a systematic review by patient category (January 2002 to August 2009), two health technology assessment (HTA) reports and thirty-eight clinical studies not covered by the HTA reports (eleven meta-analysis including ours, eleven randomized trials and sixteen cohort studies) were selected. After assessment of the methodological quality, the studies mostly comparing DES with BMS were reviewed by a panel of health professionals who defined a priori the most relevant end points of safety and efficacy. RESULTS: Seven to fourteen patients treated with DES were needed to avoid one target lesion revascularization (TLR) in patients with lesions >15 mm long, vessel diameter <3 mm, or diabetes, and with some complex lesions (total coronary occlusion, BMS in-stent restenosis multivessel disease, unprotected left main stenosis). DES appeared as safe as other alternatives over a follow-up of up to 4 years when dual antiplatelet therapy was continued for at least 1 year, but statistical power remains limited to conclude for some clinical features. CONCLUSIONS: For reimbursement, DES use should be limited to certain categories of patients. Treatment of particular cases requires a multidisciplinary approach.

Charge-charge coupling effects on dipole emitter relaxation within a classical electron-ion plasma description.

Studies of charge-charge (ion-ion, ion-electron, and electron-electron) coupling properties for ion impurities in an electron gas are carried out on the basis of a regularized electron-ion potential without short-range Coulomb divergence. This work is motivated, in part, by questions arising from recent spectroscopic measurements revealing discrepancies with present-day theoretical descriptions. Many of the current radiative property models for plasmas include only single electron-emitter collisions and neglect some or all charge-charge interactions. A molecular-dynamics simulation of dipole relaxation is proposed here to allow proper account of many electron-emitter interactions and all charge-charge couplings. As illustrations, molecular-dynamics simulations are reported for the cases of a single ion embedded in an electron plasma and for a two-component ion-electron plasma. Charge-charge coupling effects are discussed for hydrogen-like Balmer alpha lines at weak coupling conditions.

A conserved insertion in protein-primed DNA polymerases is involved in primer terminus stabilisation.

Protein-primed DNA polymerases form a subgroup of the eukaryotic-type DNA polymerases family, also called family B or alpha-like. A multiple amino acid sequence alignment of this subgroup of DNA polymerases led to the identification of two insertions, TPR-1 and TPR-2, in the polymerisation domain. We showed previously that Asp332 of the TPR-1 insertion of phi29 DNA polymerase is involved in the correct orientation of the terminal protein (TP) for the initiation of replication. In this work, the functional role of two other conserved residues from TPR-1, Lys305 and Tyr315, has been analysed. The four mutant derivatives constructed, K305I, K305R, Y315A and Y315F, displayed a wild-type 3'-5' exonuclease activity on single-stranded DNA. However, when assayed on double-stranded DNA such activity was higher than that of the wild-type enzyme. This activity led to a reduced pol/exo ratio, suggesting a defect in stabilising the primer terminus at the polymerase active site. On the other hand, although mutant polymerases K305I and Y315A were able to couple processive DNA polymerisation to strand displacement, they were severely impaired in phi29 TP-DNA replication. The possible role of the TPR-1 insertion in the set of interactions with the nascent chain during the first steps of TP-DNA replication is discussed.