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Background: Hospital at home (HaH), either admission avoidance (AA) or early supported discharge (ESD), was increasingly implemented in Catalonia (7.7 M, Spain) for selected patients, achieving regional adoption within the 2011-2015 Health Plan. This study aimed to assess population-wide HaH outcomes over five years (2015-2019) in a consolidated regional HaH program and provide context-independent recommendations for service quality assurance. Methods: A mixed-methods approach was adopted, combining population-based retrospective analyses of registry information with qualitative research. AA and ESD were separately compared with conventional hospitalization groups using propensity score matching techniques. In the analysis, we evaluated the 12-month period before the acute episode, the admission, and use of healthcare resources at 30 and 90 days after discharge. A panel of experts discussed the results and provided recommendations for monitoring HaH services. Results: The adoption of AA steadily increased from 5,185 to 8,086 episodes/year (total episodes 31,901; mean age 73 (SD 17) years; 79% high-risk patients), whereas ESD remained stable over the study period, averaging 5,329 episodes per year (total episodes 26,646; mean age 68 (SD 16) years; 71% high-risk patients). Mortality rates were similar in HaH and conventional hospitalization within the episode (AA: 0.31% vs. 0.45%; ESD: 0.18% vs. 0.45%) and at 30-days (AA: 3.94% vs. 3.24%; ESD: 4.50% vs. 4.07%). Likewise, the frequency of patients requiring hospital re-admissions or ER visits 30 days after discharge was similar in HaH (AA and ESD) and the corresponding controls. The 27 healthcare providers assessed showed high variability in patients age, multimorbidity, severity of episodes, recurrences, and length of stay of AA episodes. Recommendations aiming at enhancing service delivery were produced. Conclusions: Besides confirming safety and value generation of AA, we found that this service is delivered in a case-mix of diferent scenarios, encouraging provider-profiled monitoring of the service, particularly for ESD modalities. Keywords: Hospital at Home, Admission Avoidance, Early Supported Discharge, Implementation Science, Integrated Care.

BackgroundMany advantages of hospital at home (HaH), as a modality of acute care, have been highlighted, but controversies exist regarding the cost-benefit trade-offs.ObjectiveTo assess health outcomes and analytical costs of hospital avoidance (HaH-HA) in a consolidated service with over ten years of delivery of HaH in Barcelona (Spain).MethodsA retrospective cost-consequence analysis of all first episodes of HaH-HA, directly admitted from the emergency room (ER) in 2017–2018, was carried out. HaH-HA was compared with a propensity-score-matched group of contemporary patients admitted to conventional hospitalization (Controls). Mortality, re-admissions, ER visits, and direct healthcare costs were evaluated.RegistrationClinicalTrials.gov(26/04/2017;NCT03130283).ResultsHaH-HA and Controls (n=441 each) were comparable in terms of age (73 [SD16]vs74 [16]), gender (male, 57%vs59%), multimorbidity, healthcare expenditure during the previous year, case mix index of the acute episode, and main diagnosis at discharge. HaH-HA presented lower mortality during the episode (0 vs. 19 (4.3%);p< 0.001). At 30 days post-discharge, HaH-HA and Controls showed similar re-admission rates; however, ER visits were lower in HaH-HA than in Controls (28 (6.3%) vs 34 (8.1%); p = 0.044). Average costs per patient during the episode were lower in the HaH-HA group (€ 1,078) than in Controls (€ 2,171). Likewise, healthcare costs within the 30 days post-discharge were also lower in HaH-Ha than in Controls (p< 0.001).ConclusionsThe study showed higher performance and cost reductions of HaH-HA in a real-world setting. The identification of sources of savings facilitates scaling of hospital avoidance.FundingThis article was funded by JADECARE project- HP-JA-2019 - Grant Agreement nº951442 (2020-2023), a European Union’s Health Program 2014-2020.KEY POINTSHospital at home, modality hospital avoidance, shows high potential for value generation in real-world settings by improving health outcomes and generating cost-savings.Positive outcomes of hospital avoidance seem associated to adequate management change and digital support.

PurposeTo assess the effectiveness of an integrated care program for post-acute care of stroke patients, the return home program (RHP program), deployed in Barcelona (North-East Spain) between 2016 and 2017 in a context of health and social care information systems integration.Design/methodology/approachThe RHP program was built around an electronic record that integrated health and social care information (with an agreement for coordinated access by all stakeholders) and an operational re-design of the care pathways, which started upon hospital admission instead of discharge. The health outcomes and resource use of the RHP program participants were compared with a population-based matched control group built from central healthcare records of routine care data.FindingsThe study included 92 stroke patients attended within the RHP program and the patients' matched controls. Patients in the intervention group received domiciliary care service, home rehabilitation, and telecare significantly earlier than the matched controls. Within the first two years after the stroke episode, recipients of the RHP program were less frequently institutionalized in a long-term care facility (5 vs 15%). The use of primary care services, non-emergency transport, and telecare services were more frequent in the RHP group.Originality/valueThe authors' analysis shows that an integrated care program can effectively promote and accelerate delivery of key domiciliary care services, reducing institutionalization of stroke patients in the mid-term. The integration of health and social care information allows not only a better coordination among professionals (thus avoiding redundant assessments) but also to monitor health and resource use outcomes of care delivery.

The COVID-19 pandemic has caused a remarkable psychological overwhelming and an increase of stressors that may trigger suicidal behaviors. However, its impact on the rate of suicidal behaviors has been poorly reported. We conducted a population-based retrospective analysis of all suicidal behaviors attended in healthcare centers of Catalonia (North-East Spain; 7.5-million inhabitants) between January 2017 and June 2022. We retrieved data from the episode, including an assessment of suicide risk and the individual’s socioeconomic and clinical characteristics. Data were summarized yearly and for the periods before and after the onset of the COVID-19 pandemic in Spain in March 2020. The analysis included 26,458 episodes of suicidal behavior (21,920 individuals); of them, 16,414 (62.0%) were suicide attempts. The monthly moving average ranged between 300 and 400 episodes until July 2020, and progressively increased to over 600 episodes monthly. In the post-pandemic period, suicidal ideation increased at the expense of suicidal attempts. Cases showed a lower suicide risk; the percentage of females and younger individuals increased, whereas the prevalence of classical risk factors, such as living alone or lacking a family network and a history of psychiatric diagnosis, decreased. In summary, suicidal behaviors have increased during the COVID-19 pandemic, with more episodes of suicidal ideations without attempt and younger and lower risk profiles.

ObjectivesTo investigate whether the effect of chronological age on the risk of developing critical illness in COVID-19 hospitalized individuals is attenuated, and to which extent, when adjusting for increasingly exhaustive measures of the comorbidity burden.DesignRetrospective assessment of electronic health records.SettingAll public hospitals of the Catalan Institute of Health (Catalonia; North-East Spain; 7.7 million inhabitants), which account for 30% of all hospital admissions in Catalonia.ParticipantsWe included all individuals admitted to the hospital with COVID-19 as the main diagnosis between March 1, 2020, and January 31, 2022. Vaccinated individuals and those admitted within the first of the six COVID-19 epidemic waves were excluded from the primary analysis but were included in secondary analyses.Main outcome measuresThe primary composite outcome was critical illness, defined as the need for invasive mechanical ventilation, transfer to the intensive care unit (ICU), or in-hospital death (any of them). Explanatory variables included age, sex, and four summary measures of comorbidity burden on admission: the Charlson index (17 diagnostic group codes), the Elixhauser index and count (31 diagnostic group codes), and the Queralt DxS index (3,145 diagnostic group codes). All models were adjusted by wave and center. The proportion of the effect of age attributable to comorbidity burden was assessed using a causal mediation analysis.ResultsThe primary analysis included 10,090 hospitalizations due to COVID-19; of them, 3,524 experienced a critical illness. The frequency of critical illness increased with age and comorbidity burden on admission, irrespective of the measure used. In multivariate analyses, the effect size of age decreased with the number of diagnoses considered to estimate comorbidity burden. When adjusting for the Queralt DxS index, age showed a minimal contribution to critical illness; according to the causal mediation analysis, comorbidity burden on admission explained the 95.3% (95% CI 82.1% −112.7%) of the observed effect of age on critical illness.ConclusionsWhen measured exhaustively, comorbidity burden rather than chronological age explains the increased risk of critical illness observed in patients hospitalized with COVID-19.Summary boxWhat is already known on this topicAge is broadly acknowledged as a critical risk factor for developing critical illness in individuals hospitalized due to COVID-19.When adjusting for other underlying factors, such as comorbidities, the effect size of age for predicting critical illness decreases; nevertheless, most studies have suggested that age remains independently associated with COVID-19 outcomes.What this study addsThe observed contribution of chronological age to the risk of critical illness in hospitalized COVID-19 patients decreases with the exhaustivity of the measure of comorbidity burden.When adjusting for a comprehensive comorbidity index that considers all possible clinical conditions from a weighted list of 3,145 possible diagnostic groups, age has little or no relevant effect on the risk of critical illness.Mediation analyses confirm that the effect of chronological age on COVID-19 outcomes can be explained by comorbidity burden.

BACKGROUND Quarantines and nationwide lockdowns dictated for containing the spread of the COVID-19 pandemic may lead to distress and increase the frequency of anxiety and depression symptoms among the general population. During the national lockdown of the first wave of the COVID-19 outbreak in Spain, we developed and launched a Web App to promote emotional self-care in the general population and facilitate contact with healthcare professionals. OBJECTIVE To describe the Web App and analyse its utilization pattern throughout two successive waves of the COVID-19 outbreak in Spain. METHODS The Web App targeted all individuals aged 18 years or more and was designed by adapting the contents of a mobile App for adjuvant treatment of post-traumatic stress disorder (i.e., the PTSD Coach App) to the general population and the pandemic/lockdown scenario. We retrospectively assessed the utilization pattern of the Web App using data systematically retrieved from Google Analytics. Data were grouped into three time periods, defined using a join point analysis of COVID-19 incidence in our area: first wave, between-wave period, and second wave. RESULTS The resulting Web App, named gesioemocional.cat, maintains the navigation structure of the PTSD Coach App, with three main modules: tools for emotional self-care, a self-assessment test, and professional resources for on-demand contact. The self-assessment test combines the Patient Health Questionnaire-2 (PHQ-2) and the 7-item Generalized Anxiety Disorder Scale (GAD-7) and offers professional contact in the advent of a high level of depression and anxiety; contact is prioritized according to a screening questionnaire administered at the time of obtaining individual consent to be contacted. The tools for emotional self-care can be accessed either on-demand or symptom-driven. The utilization analysis showed a high number of weekly accesses during the first wave. In this period, press releases regarding critical events of the pandemic progression and government decisions on containment measures were followed by a utilization peak, irrespective of the sense (i.e., positive or negative) of the information. Positive information pieces (e.g., relaxation of containment measures due to a reduction of COVID-19 cases) resulted in a sharp increase in utilization immediately after information release, followed by a successive decline in utilization. The second wave was characterized by a lower and less responsive utilization of the Web App. CONCLUSIONS mHealth tools may help the general population coping with stressful conditions associated with the pandemic scenario. Future studies shall investigate the effectiveness of these tools among the general population―including individuals without diagnosed mental illnesses―and strategies to reach as many people as possible. CLINICALTRIAL Not applicable

The COVID-19 pandemic has caused remarkable psychological overwhelming and an increase in stressors that may trigger suicidal behaviors. However, its impact on the rate of suicidal behaviors has been poorly reported. We conducted a population-based retrospective analysis of all suicidal behaviors attended in healthcare centers of Catalonia (northeast Spain; 7.5 million inhabitants) between January 2017 and June 2022 (secondary use of data routinely reported to central suicide and diagnosis registries). We retrieved data from this period, including an assessment of suicide risk and individuals’ socioeconomic as well as clinical characteristics. Data were summarized yearly and for the periods before and after the onset of the COVID-19 pandemic in Spain in March 2020. The analysis included 26,458 episodes of suicidal behavior (21,920 individuals); of these, 16,414 (62.0%) were suicide attempts. The monthly moving average ranged between 300 and 400 episodes until July 2020, and progressively increased to over 600 episodes monthly. In the postpandemic period, suicidal ideation increased at the expense of suicidal attempts. Cases showed a lower suicide risk; the percentage of females and younger individuals increased, whereas the prevalence of classical risk factors, such as living alone, lacking a family network, and a history of psychiatric diagnosis, decreased. In summary, suicidal behaviors have increased during the COVID-19 pandemic, with more episodes of suicidal ideation without attempts in addition to younger and lower risk profiles.

BackgroundQuarantines and nationwide lockdowns dictated for containing the spread of the COVID-19 pandemic may lead to distress and increase the frequency of anxiety and depression symptoms among the general population. During the national lockdown of the first wave of the COVID-19 outbreak in Spain, we developed and launched a Web App (Gestioemocional.cat) to promote emotional self-care in the general population and facilitate contact with healthcare professionals.MethodsGestioemocional.cat targeted all individuals aged 18 years or more and was designed by adapting the contents of a mobile App for adjuvant treatment of post-traumatic stress disorder (i.e., the PTSD Coach App) to the general population and the pandemic/lockdown scenario. We retrospectively assessed the utilization pattern of the Web App using data systematically retrieved from Google Analytics. Data were grouped into three time periods, defined using a join point analysis of COVID-19 incidence in our area: first wave, between-wave period, and second wave.ResultsThe resulting Web App, maintains the navigation structure of the PTSD Coach App, with three main modules: tools for emotional self-care, a self-assessment test, and professional resources for on-demand contact. The self-assessment test combines the Patient Health Questionnaire-2 (PHQ-2) and the 7-item Generalized Anxiety Disorder Scale (GAD-7) and offers professional contact in the advent of a high level of depression and anxiety; contact is prioritized according to a screening questionnaire administered at the time of obtaining individual consent to be contacted. The tools for emotional self-care can be accessed either on-demand or symptom-driven. The utilization analysis showed a high number of weekly accesses during the first wave. In this period, press releases regarding critical events of the pandemic progression and government decisions on containment measures were followed by a utilization peak, irrespective of the sense (i.e., positive or negative) of the information. Positive information pieces (e.g., relaxation of containment measures due to a reduction of COVID-19 cases) resulted in a sharp increase in utilization immediately after information release, followed by a successive decline in utilization. The second wave was characterized by a lower and less responsive utilization of the Web App.ConclusionsmHealth tools may help the general population coping with stressful conditions associated with the pandemic scenario. Future studies shall investigate the effectiveness of these tools among the general population―including individuals without diagnosed mental illnesses―and strategies to reach as many people as possible.

Background: Non-attendance to scheduled hospital outpatient appointments may compromise healthcare resource planning, which ultimately reduces the quality of healthcare provision by delaying assessments and increasing waiting lists. We developed a model for predicting non-attendance and assessed the effectiveness of an intervention for reducing non-attendance based on the model.Methods: Candidate models were built using retrospective data from appointments scheduled between January 1, 2015, and November 30, 2018, in the dermatology and pneumology outpatient services of the Hospital Municipal de Badalona (Spain). The predictive capacity of the selected model was then validated prospectively with appointments scheduled between January 7 and February 8, 2019. The effectiveness of selective phone call reminders to patients at high risk of non-attendance according to the model was assessed on all consecutive patients with at least one appointment scheduled between February 25 and April 19, 2019. Patients identified by the model as high risk of non-attendance were randomly assigned to either a control (no intervention) or intervention group, the last receiving phone call reminders one week before the appointment.Results: Models were trained and selected using 33,329 appointments in the dermatology service and 21,050 in the pneumology service. Average results for specificity and balanced accuracy for the prediction of non-attendance were 79.90% and 73.49% for dermatology, and 71.38% and 64.61% for pneumology outpatient services. The prospective validation showed a specificity of 78.34% (95%CI 71.07, 84.51) and balanced accuracy of 70.45% for dermatology; and 69.83% (95%CI 60.61, 78.00) for pneumology, respectively. The effectiveness of the intervention was assessed on 1,311 individuals identified as high risk of non-attendance according to the selected model. Overall, the intervention resulted in a significant reduction in the non-attendance rate to both the dermatology and pneumology services, with a decrease of 50.61% (pp=0.048), respectively.Conclusions: The risk of non-attendance can be adequately estimated using patient information stored in medical records. The patient stratification according to the non-attendance risk allows prioritizing interventions, such as phone call reminders, to effectively reduce non-attendance rates.

BackgroundComorbidity burden has been identified as a relevant predictor of critical illness in patients hospitalized with coronavirus disease 2019 (COVID-19). However, comorbidity burden is often represented by a simple count of few conditions that may not fully capture patients’ complexity.PurposeTo evaluate the performance of a comprehensive index of the comorbidity burden (Queralt DxS), which includes all chronic conditions present on admission, as an adjustment variable in models for predicting critical illness in hospitalized COVID-19 patients and compare it with two broadly used measures of comorbidity.Patients and methodsWe analyzed data from all COVID-19 hospitalizations reported in eight public hospitals of Catalonia (North-East Spain) between June 15 and December 8 2020. The primary outcome was a composite of critical illness that included the need for invasive mechanical ventilation, transfer to ICU, or in-hospital death. Predictors included age, sex, and comorbidities present on admission measured using three indices: the Charlson index, the Elixhauser index, and the Queralt DxS index for comorbidities on admission. The performance of different fitted models was compared using various indicators, including the area under the receiving operating characteristics curve (AUC).ResultsOur analysis included 4,607 hospitalized COVID-19 patients. Of them, 1,315 experienced critical illness. Comorbidities significantly contributed to predicting the outcome in all summary indices used. The AUC for prediction of critical illness was 0.641 (95% CI 0.624-0.660) for the Charlson index, 0.665 (0.645-0.681) for the Elixhauser index, and 0.787 (0.773-0.801) for Queralt DxS. Other metrics of model performance also showed Queralt DxS being consistently superior to the other indices.ConclusionIn our analysis, the ability of comorbidity indices to predict hospital outcomes in hospitalized COVID-19 patients increased with their exhaustivity. The comprehensive Queralt DxS index may improve the accuracy of predictive models for resource allocation and clinical decision-making in the hospital setting.

The shortage of recently approved vaccines against the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has highlighted the need for evidence-based tools to prioritize healthcare resources for people at higher risk of severe coronavirus disease 2019 (COVID-19). Current evidence indicates that age is far from accurate in identifying the risk of severe illness; furthermore, the count of individual risk factors has limited applicability to population-based “stratify-and-shield” strategies. We developed a COVID-19 risk stratification system that allows allocating people into four mutually-exclusive risk categories based on multivariate models for hospital admissions, transfer to intensive care unit (ICU), and mortality among the general population. The model was developed using clinical, hospital, and epidemiological data from the entire population of Catalonia (North-East Spain; 7.5 million people) and validated using an independent dataset of 218,329 individuals with PCR-confirmed COVID-19, who were infected after developing the model. This showed high discrimination capacity, with an area under the curve of the receiving operating characteristics of 0.85 (95% CI 0.85–0.85) for hospital admissions, 0.86 (0.86–0.97) for ICU transfers, and 0.96 (0.96–0.96) for deaths. Our results provide clinicians and policymakers with an evidence-based tool for prioritizing COVID-19 healthcare resources other population groups aside from those with higher exposure to SARS-CoV-2 and frontline workers.

BACKGROUND Quarantines and nationwide lockdowns implemented for containing the spread of the COVID-19 pandemic may lead to distress and increase the frequency of anxiety and depression symptoms among the general population. During the nationwide lockdown of the first wave of the COVID-19 outbreak in Spain, we developed and launched a web-based app to promote emotional self-care in the general population and facilitate contact with health care professionals. OBJECTIVE This study aimed to describe a web-based app and analyze its utilization pattern throughout 2 successive waves of the COVID-19 outbreak in Spain. METHODS Our web-based app targeted all individuals aged 18 years or more and was designed by adapting the contents of a mobile app for adjuvant treatment of posttraumatic stress disorder (ie, the PTSD Coach app) to the general population and the pandemic or lockdown scenario. We retrospectively assessed the utilization pattern of the web-based app using data systematically retrieved from Google Analytics. Data were grouped into 3 time periods, defined using Joinpoint regression analysis of COVID-19 incidence in our area: first wave, between-wave period, and second wave. RESULTS The resulting web-based app, named gesioemocional.cat, maintains the navigation structure of the PTSD Coach app, with three main modules: tools for emotional self-care, a self-assessment test, and professional resources for on-demand contact. The self-assessment test combines the Patient Health Questionnaire-2 and the 7-item Generalized Anxiety Disorder scale and offers professional contact in the advent of a high level of depression and anxiety; contact is prioritized in accordance with a screening questionnaire administered at the time of obtaining individual consent to be contacted. The tools for emotional self-care can be accessed either on-demand or symptom-driven. The utilization analysis showed a high number of weekly accesses during the first wave. In this period, press releases regarding critical events of the pandemic progression and government decisions on containment measures were followed by a utilization peak, irrespective of the sense (ie, positive or negative) of the information. Positive information pieces (eg, relaxation of containment measures due to a reduction of COVID-19 cases) resulted in a sharp increase in utilization immediately after information release, followed by a successive decline in utilization. The second wave was characterized by a lower and less responsive utilization of the web-based app. CONCLUSIONS mHealth tools may help the general population cope with stressful conditions associated with the pandemic scenario. Future studies shall investigate the effectiveness of these tools among the general population—including individuals without diagnosed mental illnesses—and strategies to reach as many people as possible.

BackgroundMultimorbidity measures are useful for resource planning, patient selection and prioritization, and factor adjustment in clinical practice, research, and benchmarking. We aimed to compare the explanatory performance of the adjusted morbidity group (GMA) index in predicting relevant healthcare outcomes with that of other quantitative measures of multimorbidity.MethodsThe performance of multimorbidity measures was retrospectively assessed on anonymized records of the entire adult population of Catalonia (North-East Spain). Five quantitative measures of multimorbidity were added to a baseline model based on age, gender, and socioeconomic status: the Charlson index score, the count of chronic diseases according to three different proposals (i.e., the QOF, HCUP, and Karolinska institute), and the multimorbidity index score of the GMA tool. Outcomes included all-cause death, total and non-scheduled hospitalization, primary care and ER visits, medication use, admission to a skilled nursing facility for intermediate care, and high expenditure (time frame 2017). The analysis was performed on 10 subpopulations: all adults (i.e., aged > 17 years), people aged > 64 years, people aged > 64 years and institutionalized in a nursing home for long-term care, and people with specific diagnoses (e.g., ischemic heart disease, cirrhosis, dementia, diabetes mellitus, heart failure, chronic kidney disease, and chronic obstructive pulmonary disease). The explanatory performance was assessed using the area under the receiving operating curves (AUC-ROC) (main analysis) and three additional statistics (secondary analysis).ResultsThe adult population included 6,224,316 individuals. The addition of any of the multimorbidity measures to the baseline model increased the explanatory performance for all outcomes and subpopulations. All measurements performed better in the general adult population. The GMA index had higher performance and consistency across subpopulations than the rest of multimorbidity measures. The Charlson index stood out on explaining mortality, whereas measures based on exhaustive definitions of chronic diagnostic (e.g., HCUP and GMA) performed better than those using predefined lists of diagnostics (e.g., QOF or the Karolinska proposal).ConclusionsThe addition of multimorbidity measures to models for explaining healthcare outcomes increase the performance. The GMA index has high performance in explaining relevant healthcare outcomes and may be useful for clinical practice, resource planning, and public health research.

Fatty acyl-CoA reductases (FARs), the enzymes that catalyse reduction of a fatty acyl-CoA to the corresponding alcohol in insect pheromone biosynthesis, are postulated to play an important role in determining the proportion of each component in the pheromone blend. For the first time, we have isolated and characterized from the Egyptian cotton leaf worm Spodoptera littoralis (Lepidoptera: Noctuidae) a FAR cDNA (Slit-FAR1), which appeared to be expressed only in the pheromone gland and was undetectable in other female tissues, such as fat body, ovaries, wings, legs or thorax. The encoded protein has been successfully expressed in a recombinant system, and the recombinant enzyme is able to produce the intermediate fatty acid alcohols of the pheromone biosynthesis of S. littoralis from the corresponding acyl-CoA precursors. The kinetic variables Km and Vmax, which have been calculated for each acyl-CoA pheromone precursor, suggest that in S. littoralis pheromone biosynthesis other biosynthetic enzymes (e.g. desaturases, acetyl transferase) should also contribute to the final ratio of components of the pheromone blend. In a phylogenetic analysis, Slit-FAR1 appeared grouped in a cluster of other FARs involved in the pheromone biosynthesis of other insects, with little or non-specificity for the natural pheromone precursors.

Infochemical production, release and detection of (Z,E)-9,11-tetradecadienyl acetate, the major component of the pheromone of the moth Spodoptera littoralis is achieved in a novel microfluidic system, designed to mimic the final step of the pheromone biosynthesis by immobilized recombinant alcohol acetyl transferase. The microfluidic system is part of an "artificial gland", i.e. a chemoemitter that comprises a microreactor connected to a microevaporator and is able to produce and release a pre-defined amount of the major component of the pheromone from the corresponding (Z,E)-9,11-tetradecadienol.. Performance of the entire chemoemitter has been assessed in electrophysiological and behavioral experiments. Electroantennographic depolarizations of the pheromone produced by the chemoemitter were ca. 40% relative to that evoked by the synthetic pheromone. In a wind tunnel, the pheromone released from the evaporator elicited on males a similar attraction behaviour as 3 virgin females in most of the parameters considered.

We explore the functionality of a complete chemoemitter platform mimicking the biosynthetic pathways and release of female sex pheromones of the Spodoptera littoralis moth. This artificial gland system consists of a microreactor in which the pheromone biosynthesis takes place, and a micromachined evaporator that releases ratiometrically-encoded blend into the environment. The artificial gland was implemented for the investigation and detection of patterns by highly sensitive olfaction system of male moths in electroantennographic and behavioral assays. Thus, a new information emission scheme by utilizing semiochemicals as a data carrier was demonstrated.

To prepare a biosynthetic module in an infochemical communication project, we designed a silicon/glass microreactor with anti-adsorption polyelectrolyte multilayer coating and immobilized alcohol acetyl transferase (atf), one of the key biosynthetic enzymes of the pheromone of Spodoptera littoralis, on agarose beads inside. The system reproduces the last step of the biosynthesis in which the precursor diene alcohol (Z,E)-9,11-tetradecadienol is transformed into the major component (Z,E)-9,11-tetradecadienyl acetate. The scope of this study was to analyze and implement a multilayer, anti-adsorption coating based on layer-by-layer deposition of polyethylenimine/dextransulfate sodium salt (PEI/DSS). The multilayers were composed of two PEI with molecular weights 750 and 1.2 kDa at pH 9.2 or 6.0. Growth, morphology, and stability of the layers were analyzed by ellipsometry and atomic force microscopy (AFM). The anti-adsorption functionality of the multilayer inside the microreactor was validated. The activity of His6-(atf) was measured by gas chromatography coupled to mass spectrometer (GC-MS).

Background: Carboxyl/cholinesterases (CCEs) are highly diversified in insects. These enzymes have a broad range of proposed functions, in neuro/developmental processes, dietary detoxification, insecticide resistance or hormone/ pheromone degradation. As few functional data are available on purified or recombinant CCEs, the physiological role of most of these enzymes is unknown. Concerning their role in olfaction, only two CCEs able to metabolize sex pheromones have been functionally characterized in insects. These enzymes are only expressed in the male antennae, and secreted into the lumen of the pheromone-sensitive sensilla. CCEs able to hydrolyze other odorants than sex pheromones, such as plant volatiles, have not been identified. Methodology: In Spodoptera littoralis, a major crop pest, a diversity of antennal CCEs has been previously identified. We have employed here a combination of molecular biology, biochemistry and electrophysiology approaches to functionally characterize an intracellular CCE, SlCXE10, whose predominant expression in the olfactory sensilla suggested a role in olfaction. A recombinant protein was produced using the baculovirus system and we tested its catabolic properties towards a plant volatile and the sex pheromone components. Conclusion: We showed that SlCXE10 could efficiently hydrolyze a green leaf volatile and to a lesser extent the sex pheromone components. The transcript level in male antennae was also strongly induced by exposure to this plant odorant. In antennae, SlCXE10 expression was associated with sensilla responding to the sex pheromones and to plant odours. These results suggest that a CCE-based intracellular metabolism of odorants could occur in insect antennae, in addition to the extracellular metabolism occurring within the sensillar lumen. This is the first functional characterization of an Odorant- Degrading Enzyme active towards a host plant volatile., This work was supported by Universite´ Pierre et Marie Curie (UPMC), INRA, ANR-07-NEURO-037-01 funding and a fellowship from the Research Ministry to N. Durand. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

International audience; Rapid degradation of odours after interaction with olfactory receptors is a critical step of the signal reception process. However, the implied mechanisms are still largely unknown in vertebrates as well as in insects. Involvement of odourant-degrading enzymes in odourant degradation within the antennae has been shown in some insect species and, in particular, esterases could play a key role in degradation of sex pheromones from Lepidoptera. Using a PCR-based strategy, we isolated cDNAs encoding two new esterases from two moths which used acetates as pheromone compounds: the Egyptian armyworm Spodoptera littoralis and the Mediterranean corn borer Sesamia nonagrioides. In antennae, both transcripts were clearly restricted to olfactory sensilla, suggesting their involvement in the degradation of odourant acetate components.