Reusable laryngoscope blades: a more eco-responsible and cost-effective alternative.

INTRODUCTION: Consumption of single-use medical devices has increased considerably, contributing to the excessive wastage produced during surgical procedures. The present study aimed to describe a methodology to assess the transition from single-use blades (SUB) to reusable laryngoscope blades (RUB) and to assess the ecological and economic impact of the switch. METHODS: The ecological analysis was based on the life cycle assessment method. Based on 30 operating rooms in a single tertiary university hospital, the economic analysis compared the usual SUB supplier with four RUB suppliers considering different costs: blade purchasing and depreciation, reprocessing, logistics and waste management. RESULTS: In 2021, 17,200 intubations were performed requiring about 147 RUBs. Switching from SUB to RUB led to an annual saving of 26.5 tons of CO2eq (global warming impact), equivalent to 120 000 km by car. It avoids the extraction of 6.6 tons Oileq (petroleum) and 579 kg of copper (mineral resources) per year. This action also leads to a land occupation reduction of 626 m2 per year and water savings of 221.6 m3 per year. The average cost per intubation varies from 3.16 [3.15-3.16] for SUB to 2.81 [2.77-2.85] for RUB, representing an average saving of 0.35 per intubation leading to 5783.50 annual gain [5074.00-6192.00]. RUB are preferable from 3 and 86 uses from an ecological and economic viewpoint, respectively. CONCLUSION: In a model of 17,200 intubations /year, switching SUD to RUB would save 26.5 tons of CO2eq and 6.6 tons of Oileq with 5783.50 annual gain. RUBs are ecologically and cost-effective after 3 and 86 uses, respectively.

Ecoresponsible actions in operating rooms: A health ecological and economic evaluation.

BACKGROUND: In the current context of climate change, actions must be taken to improve the hospital's ecological footprint, particularly in the operating room, which is a major consumer of medical devices. METHODS: This prospective pilot study assessed the ecological and economic impacts of sustainable actions targeting medical devices designed by a multidisciplinary working group and implemented in the 24 operating rooms of a University Hospital over one year. The ecological analysis was based on the life cycle assessment method and categorized in seven impacts. The economic impact was assessed by a micro-costing analysis and divided in four main expense items: human and material resources, logistics, and waste management. RESULTS: In total, 13 actions were implemented with the aim of reducing waste volume, improving waste sorting, and increasing eco-responsible purchases. In one year, these 13 actions allowed avoiding the emission of 203 tons eq CO2. The environmental and human toxicity benefits were 707.8 and 156.2 tons of 1.4 dichlorobenzene, respectively. Concerning non-renewable resources, these actions avoided the extraction of 9 tons of oil (petroleum) and 610 kg of copper per year. These actions led to a land occupation reduction of 1071.3 m2year and to water saving of 552 m3. From the economic side, the implementation of these actions brought a gain of €3747.9 for the first year and of €5188.2 for the following years. CONCLUSION: The integration of sustainable measures in operating rooms leads to important ecological benefits and also generating savings. This more eco-responsible approach should be considered in all healthcare establishments that generate a significant annual volume of waste.

[Suicide attempts by young adolescents: epidemiological characteristics of 517 15-year-old or younger adolescents admitted in French emergency departments]. / Tentatives de suicide: étude descriptive d'une cohorte de 517 adolescents de moins de 15 ans et 3 mois.

Adolescents who attempt suicide are a major concern. A growing body of literature seeks to explain this phenomenon and to identify its predictive factors, but relatively little information is available and children and adolescents under 15 years of age who present to general hospitals because of a suicide attempt. This study aimed to describe the demographic, social, medical, and psychological characteristics of a large sample of 517 French adolescents aged not more than 15 years 3 months. A second purpose was to measure observance of psychological care in a 1-year follow-up. Third, we aimed to document the reattempt rate during the follow-up in this population of young adolescents. Following the French official recommendations, a systematic 72-h hospitalization as well as a somatic, social, and psychological assessment was proposed to every suicide attempter after his or her admission to the emergency department. The adolescent was followed for 1 year after the suicide attempt, called the index episode. This follow-up was organized by two physicians, one of whom was not associated with the care of any of the patients. It consisted in seeking regular information as well as organization and/or optimization of the patient's psychological care, which was delivered in dedicated structures for adolescents, in outpatient care by a psychiatrist, or in an adolescent psychiatric inpatient care unit. In case of a repeated suicide attempt or persistence of alarming symptoms, this follow-up was prolonged for 1 more year. Patient data were compiled by experienced clinicians during initial assessment and alongside the 1-year follow-up through patient self-reports, but also through interviews with informants (family members, social professionals) and clinical sources (general practitioner, psychiatrist, etc.). The areas covered were the characteristics of the index episode, those of the population at the time of the index episode, as well as those of the 1-year follow-up including observance to the care and potential repetition of the suicide attempt. The mean age was 14 years with a minimum of 7 years 9 months. The vast majority of the population was female (86.1%), less than one-third lived with both parents, and 27% had academic problems. The most frequent means of suicide attempt was medication (83.9%), 92.6% of adolescents were hospitalized following the index episode, only 7.5% of them were admitted to adolescent psychiatric unit inpatient care following the initial care. Psychiatric evaluation was documented for 93.3% of the adolescents. Half (n=222) had at least one symptom of a psychiatric disorder. One-year follow-up data were available for 394 adolescents: 40 had not yet completed the year and 83 were lost to follow-up. Among the analyzable population of 391 adolescents, 35.3% were optimally observant of the care proposed and 21.4% did not observe treatment. Fifty-nine youths (15%) were referred to the hospital because of a repeated suicide attempt. Two of the patients who repeated the suicide attempt within the year had died. The findings from this study are informative with regard to prevention and intervention efforts with suicidal young and very young adolescents. First, repetition of the suicide attempt in young adolescents is not rare since nearly 15% of the cohort were repeaters within the year following the index episode. Nevertheless, intensive care and follow-up resulting in good attendance appeared to have a positive impact on the repetition of the suicide attempt.

[Schizophrenia and cognition: a neurodevelopmental approach]. / Schizophrénie et cognition: perspective neurodéveloppementale.

Accumulating evidence supports the hypothesis of abnormal neurodevelopment in schizophrenia. According to this hypothesis, schizophrenia is the consequence of prenatal abnormalities resulting from the interaction of genetic and environmental factors. In line with this hypothesis, several studies indicate that pregnancy and birth complications are risk factors for developing schizophrenia. At the clinical level, multiple cognitive deficits can be found in schizophrenic patients before illness onset. The neurodevelopmental hypothesis considers these cognitive deficits as the expression of early abnormalities on the central nervous system development. Consistently, brain imaging data show early structural abnormalities and abnormal progressive brain changes in schizophrenia. Finally, genetic and histological data indicate that genes associated with schizophrenia are involved in brain development.

[Bipolar disorder: Continuity from child to adult?]. / Troubles bipolaires : continuité enfant-adulte ?

Early onset (pediatric) bipolar disorders are still an issue of much controversy due to several clinical particularities of the thymic episodes at this age. To date, there is indeed no consensus regarding the prevalence of bipolar disorders before puberty. Diagnosis criteria in children and young adolescents remain thus elusive. The purpose of this review is to provide an overview of this issue. The idea of continuity, from childhood to adulthood, in bipolar disorders also raises important questions regarding predictive factors of bipolar disorders in adults. Studies on the childhood of bipolar adults, as well as studies on the children of bipolar parents will be reviewed, in an attempt to identify the psychopathological substrates of bipolar disorders.

Wavelength-resolved fluorescence emission of proteins using the synchrotron radiation as pulsed-light source: cross-correlations between lifetimes, rotational correlation times and tryptophan heterogeneity in FKBP59 immunophilin.

The time-resolved fluorescence intensity and anisotropy decays of the immunophilin domain of FKBP59 (FKBP59-I)--a protein containing two tryptophan residues (the W89, buried in a hydrophobic pocket and the W59, water exposed)--were studied using the time-correlated single photon counting (TCSPC) technique. The synchrotron radiation machine Super-ACO (Orsay, France) was used as a pulsed light source (approximately 8MHz). A mainly dual and discrete excited state lifetime distribution was previously evidenced (Rouvière et al., 1997). The lifetime heterogeneity has been suggested to be relevant to the topological tryptophan heterogeneity. Indeed, taking into account the spectroscopic properties of the single tryptophan residue of the immunophilin FKBP12, a highly homologous protein containing a single tryptophan residue, the short- and the long-lived lifetime species were assumed to be related to the solvent-buried and to the solvent-exposed fluorescent residues, respectively. We definitely demonstrate this point by describing the dynamical properties of each tryptophan residue of the FKBP59-I as a function of the emission wavelength. The data of the polarized components of the fluorescence emission were analyzed by the Maximum Entropy Method using a one-dimensional model (each excited-state lifetime tau being associated with each rotational correlation time theta) and a two-dimensional model (without any a priori association constraint between the tau's and the theta's). The two dimensional analysis of the polarized fluorescence intensity decays by MEM show the existence of a correlation between fast picosecond dynamics of the indole ring with the shortest-lived and blue emitting species. Conversely, the long-lived and red emitting population is mainly associated to the Brownian motion of the protein. A protein flexibility of the region located around the W59 residue, but slightly contributing to the light depolarization process, is also evidenced and can be specifically attributed to the red emitting population.

Molecular interpretation of inhibition by excess substrate in flavocytochrome b2: a study with wild-type and Y143F mutant enzymes.

The crystal structure of flavocytochrome b2 (L-lactate dehydrogenase) from Saccharomyces cerevisiae suggests that Tyr143 plays a dual role at the active site: it contributes to substrate binding and, most importantly, makes a hydrogen bond to a heme propionate, which could facilitate communication between the domains. Previous work on the Y143F mutant enzyme provided support for these hypotheses [Miles, C. S., Rouvière-Fourmy, N., Lederer, F., Mathews, F. S., Reid, G. A., Black, M. T., & Chapman, S. K. (1992) Biochem. J. 285, 187-192; Rouvière-Fourmy, N., Capeillère-Blandin, C., & Lederer, F. (1994) Biochemistry 33, 798-806]. In the course of kinetic comparisons between the wild-type (WT) enzyme and the Y143F mutant protein, we observed for the latter signs of inhibition by excess substrate at much lower concentrations than observed for the former. A detailed investigation of the phenomenon has shown that, for the wild-type and Y143F forms, lactate at high concentrations inhibits both cytochrome c and ferricyanide reduction. In these cases, inhibition appears to be a specific effect, since acetate at identical concentrations exerts an inhibitory effect that is markedly weaker than that of lactate. In the pre-steady-state, in the absence of acceptor, flavin and heme reduction are unaffected by high substrate concentrations in the WT enzyme case. For the Y143F mutant, flavin reduction is similarly unaffected, but heme reduction is inhibited to nearly the same extent by high lactate and acetate concentrations. In this case, inhibition can probably be ascribed to ionic strength effects. The combination of stopped-flow and steady-state results suggests that lactate binds with weak affinity at the active site when the flavin is in the semiquinone state, preventing electron transfer to heme b2 and hence to acceptors. This phenomenon is analogous to the inhibition exerted by pyruvate when bound to the enzyme at the semiquinone stage [Tegoni, M., Janot, J. M., & Labeyrie, F. (1990) Eur. J. Biochem. 190, 329-342]. We suggest that the substrate carboxylate and the heme propionate of the mobile heme-binding domain compete for the Tyr143 hydroxyl group, hence for approach to the flavin. In the Y143F mutant enzyme, in which the interdomain interaction is impaired, competition would play in favor of the substrate, resulting in the inhibition at lower lactate concentrations than observed for the wild-type enzyme.

Immunosuppressor binding to the immunophilin FKBP59 affects the local structural dynamics of a surface beta-strand: time-resolved fluorescence study.

The interaction of the immunophilin domain of FKBP59 (FKBP59-I) with immunosuppressant drugs was investigated by steady-state and time-resolved fluorescence of tryptophan. One of the two Trp residues present in this protein (W89), conserved in almost all immunophilins, is buried in the hydrophobic core and participates in the immunosuppressant binding. By comparison with the highly homologous protein FKBP12, containing only the buried Trp, it has been concluded that its weak fluorescence is due to an atypical H-bond interaction involving the indole nitrogen and the Phe129 benzene ring. The second Trp residue (W59) in FKBP59-I is located on the external hydrophilic side of the 50-60 beta-sheet [Craescu, C. T., Rouvière, N., Popescu, A., Cerpolini, E., Lebeau, M.-C., Baulieu, E.-E., & Mispelter, J. (1996) Biochemistry 35, 11045-11052] and is responsible for >95% of the fluorescence emission. The long lifetime of the major excited state, the large activation energy of thermal quenching, and the rotational correlation time distribution pattern suggest that its environment is not highly mobile. Binding of the immunosuppressant drugs FK506 and rapamycin leads to a approximately 60% decrease of the fluorescence intensity without any change in the fluorescence emission maximum. Time-resolved measurements show that this "quenching" is due to a conformational change which depletes the long excited-state lifetime population to the profit of a more quenched minor excited state, which becomes prominent in the complexes. This is accompanied by a strong slowing of the indole ring dynamics in the case of FK506 and by a complete immobilization in the case of rapamycin, as shown by two-dimensional (tau, theta) maximum entropy analysis of the polarized fluorescence decays. Binding of the immunosuppressant drugs therefore modifies the structure and the dynamics of the external side of the 50-60 beta-sheet in FKBP59-I, which could be relevant for the formation of ternary complexes with other protein targets.

Three-dimensional structure of the immunophilin-like domain of FKBP59 in solution.

FKBP59 is a protein usually associated with heat-shock protein hsp90 and steroid receptors. The N-terminal domain of the rabbit liver protein (149 amino acids) has a sequence homology with FKBP12, binds FK506 immunosuppressor, and has a peptidyl-prolyl cis-trans isomerase activity. The three-dimensional structure of this domain (FKBP59-I) was determined using homo- and heteronuclear multidimensional NMR spectroscopy, distance geometry, and molecular dynamics methods. Structure calculations used 1290 interproton distance restraints derived from nuclear Overhauser enhancement measurements, 29 dihedral phi angle restraints, and 92 hydrogen bond restraints. For the final 22 structures, the root mean square distance from the mean atomic coordinates, calculated for well-defined secondary structure fragments, is 0.47 +/- 0.05 and 1.26 +/- 0.15 A for backbone heavy atoms (N, C alpha, C') and for all non-hydrogen atoms, respectively. The global fold contains a twisted six-stranded antiparallel beta-sheet and a short alpha-helix packed on the hydrophobic side of the sheet. The 20 N-terminal and 12 C-terminal amino acids of the domain are disordered. The main-chain structure of FKBP59-I is globally similar to the NMR-derived and X-ray structures of unbound FKBP12. An unusual hydrogen bond interaction between the indole amino proton of Trp 89 and the aromatic cycle of Phe 129 was observed. This gives a large upfield shift (-4.8 ppm) and a significant exchange protection factor. The implications of the present structure determination on the ligand binding of FKBP59 are discussed.