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This study aims at investigating the chemical composition of root, stem and leaf essential oils from Ivorian Synedrella nodiflora, with the root oil being described for the first time. Sixty, fifty-one and forty-nine constituents were, respectively identified in the root, stem and leaf oils using a combination of GC(RI), GC-MS and 13C-NMR analyses. They accounted for 95.6–97.3%, 92.6–97.6% and 93.3–98.8% of the total composition, respectively. The main components of the root oil samples were γ-curcumene, (E)-β-caryophyllene, α-curcumene and curcuphenyl acetate. Three stem oil samples (S1, S2a, S3) were dominated by myrcene and limonene, while the most abundant components of sample S2b were thymol, germacrene D and β-elemene. (E)-β-caryophyllene and germacrene D were the major compounds of the leaf oil. Hierarchical cluster and principal component statistical analyses were performed and confirmed that the location does not influence the chemical composition. Group I consisted of the seven leaf oil samples, group II consisted of four stem oil samples and group III consisted of three root oil samples. The root oil composition differed considerably from the stem and leaf oil composition due to the presence of curcumene derivatives as major constituents. The leaf oil showed significant amounts of (E)-β-caryophyllene and germacrene D, while the stem oil stood out for its high myrcene, limonene and thymol contents.

Summary: Background: In industrialized countries, the incidence of inflammatory bowel disease (IBD) appears stabilized. This study examined the incidence and phenotype of IBD in Northern France over a 30-year period. Methods: Including all IBD patients recorded in the EPIMAD population-based registry from 1988 to 2017 in Northern France, we described the incidence and clinical presentation of IBD according to age, sex and time. Findings: A total of 22,879 incident IBD cases were documented (59% (n = 13,445) of Crohn’s disease (CD), 38% (n = 8803) of ulcerative colitis (UC), 3% (n = 631) of IBD unclassified (IBDU)). Over the study period, incidence of IBD, CD and UC was 12.7, 7.2 and 5.1 per 105 person-years, respectively. The incidence of CD increased from 5.1/105 in 1988–1990 to 7.9/105 in 2015–2017 (annual percent change (APC): +1.9%, p

The HOPE score (https://www.hypothermiascore.org) is a validated instrument for estimating the survival probability of patients in hypothermic cardiac arrest with ECLS rewarming. It is based on six patient characteristics: sex, age, mechanism of hypothermia, duration of cardiopulmonary resuscitation, serum potassium and temperature. The HOPE score provides a reliable estimate of survival probability that can be used to decide whether to rewarm a patient. In the initial publication of the HOPE score, a cutoff of 10% was proposed, below which a patient would not be rewarmed. This choice was tentative and subject to debate. In this paper, we examine the implications of this choice on the proportions of false positives (i.e., rewarmed patient who ends up dying) and false negatives (i.e., non-rewarmed patients who would have survived if rewarmed), and we provide approximate formulas to obtain upper bounds for these proportions as a function of the cutoff chosen. In particular, the choice of a 10% cutoff will result in a proportion of FP of less than 40% and a proportion of FN of less than 0.5% in many practical situations.

Abstract Background Suspension syndrome describes a multifactorial cardio-circulatory collapse during passive hanging on a rope or in a harness system in a vertical or near-vertical position. The pathophysiology is still debated controversially. Aims The International Commission for Mountain Emergency Medicine (ICAR MedCom) performed a scoping review to identify all articles with original epidemiological and medical data to understand the pathophysiology of suspension syndrome and develop updated recommendations for the definition, prevention, and management of suspension syndrome. Methods A literature search was performed in PubMed, Embase, Web of Science and the Cochrane library. The bibliographies of the eligible articles for this review were additionally screened. Results The online literature search yielded 210 articles, scanning of the references yielded another 30 articles. Finally, 23 articles were included into this work. Conclusions Suspension Syndrome is a rare entity. A neurocardiogenic reflex may lead to bradycardia, arterial hypotension, loss of consciousness and cardiac arrest. Concomitant causes, such as pain from being suspended, traumatic injuries and accidental hypothermia may contribute to the development of the Suspension Syndrome. Preventive factors include using a well-fitting sit harness, which does not cause discomfort while being suspended, and activating the muscle pump of the legs. Expediting help to extricate the suspended person is key. In a peri-arrest situation, the person should be positioned supine and standard advanced life support should be initiated immediately. Reversible causes of cardiac arrest caused or aggravated by suspension syndrome, e.g., hyperkalaemia, pulmonary embolism, hypoxia, and hypothermia, should be considered. In the hospital, blood and further exams should assess organ injuries caused by suspension syndrome.

Abstract Background The aim was to investigate the feasibility of a shortened dynamic whole-body (dWB) FDG-PET/CT protocol and Patlak imaging using a population-based input function (PBIF), instead of an image-derived input function (IDIF) across the 60-min post-injection period, and study its effect on the FDG influx rate (Ki) quantification in patients with metastatic melanoma (MM) undergoing immunotherapy. Methods Thirty-seven patients were enrolled, including a PBIF modeling group (n = 17) and an independent validation cohort (n = 20) of MM from the ongoing prospective IMMUNOPET2 trial. All dWB-PET data were acquired on Vision 600 PET/CT systems. The PBIF was fitted using a Feng’s 4-compartments model and scaled to the individual IDIF tail’s section within the shortened acquisition time. The area under the curve (AUC) of PBIFs was compared to respective IDIFs AUC within 9 shortened time windows (TW) in terms of linear correlation (R 2) and Bland–Altman tests. Ki metrics calculated with PBIF vs IDIF on 8 organs with physiological tracer uptake, 44 tumoral lesions of MM and 11 immune-induced inflammatory sites of pseudo-progression disease were also compared (Mann–Whitney test). Results The mean ± SD relative AUC bias was calculated at 0.5 ± 3.8% (R 2 = 0.961, AUCPBIF = 1.007 × AUCIDIF). In terms of optimal use in routine practice and statistical results, the 5th–7th pass (R 2 = 0.999 for both Ki mean and Ki max) and 5th–8th pass (mean ± SD bias = − 4.9 ± 6.5% for Ki mean and − 4.8% ± 5.6% for Ki max) windows were selected. There was no significant difference in Ki values from PBIF5_7 vs IDIF5_7 for physiological uptakes (p > 0.05) as well as for tumor lesions (mean ± SD Ki IDIF5_7 3.07 ± 3.27 vs Ki PBIF5_7 2.86 ± 2.96 100ml/ml/min, p = 0.586) and for inflammatory sites (mean ± SD Ki IDIF5_7 1.13 ± 0.59 vs Ki PBIF5_7 1.13 ± 0.55 100ml/ml/min, p = 0.98). Conclusion Our study showed the feasibility of a shortened dWB-PET imaging protocol with a PBIF approach, allowing to reduce acquisition duration from 70 to 20 min with reasonable bias. These findings open perspectives for its clinical use in routine practice such as treatment response assessment in oncology.

Objective We aimed to determine the feasibility of quality indicators (QIs) for prehospital advanced airway management (PAAM) from a provider point of view.Design The study is a survey based feasibility assessment following field testing of QIs for PAAM.Setting The study was performed in two physician staffed emergency medical services in Switzerland.Participants 42 of the 44 emergency physicians who completed at least one case report form (CRF) dedicated to the collection of the QIs on PAAM between 1 January 2019 and 31 December 2021 participated in the study.Intervention The data required to calculate the 17 QIs was systematically collected through a dedicated electronic CRF.Primary and secondary outcome measures Primary outcomes were provider-related feasibility criteria: relevance and acceptance of the QIs, as well as reliability of the data collection. Secondary outcomes were effort to collect specific data and to complete the CRF.Results Over the study period, 470 CRFs were completed, with a median of 11 per physician (IQR 4–17; range 1–48). The median time to complete the CRF was 7 min (IQR 3–16) and was considered reasonable by 95% of the physicians. Overall, 75% of the physicians assessed the set of QIs to be relevant, and 74% accepted that the set of QIs assessed the quality of PAAM. The reliability of data collection was rated as good or excellent for each of the 17 QIs, with the lowest rated for the following 3 QIs: duration of preoxygenation, duration of laryngoscopy and occurrence of desaturation during laryngoscopy.Conclusions Collection of QIs on PAAM appears feasible. Electronic medical records and technological solutions facilitating automatic collection of vital parameters and timing during the procedure could improve the reliability of data collection for some QIs. Studies in other services are needed to determine the external validity of our results.

The research focused on simulating wind patterns in urban planning design offers substantial contributions to both the social and economic aspects of the urban planning and design field. To begin with, it addresses a critical factor in urban development, especially in Mediterranean climates, where natural ventilation significantly influences summer comfort. By incorporating predictive numerical simulations of urban wind patterns, this study provides valuable insights into improving outdoor thermal comfort within urban areas. This holds particular importance in the context of adapting to climate change, as it equips urban planners and architects with informed decision-making tools to create more sustainable and comfortable urban environments. Additionally, this research makes an economic contribution by presenting guidelines for iterative wind simulations in the early stages of designing medium-scale urban projects. Through the validation of a simulation workflow, it streamlines the design process, potentially reducing the time and resources required for urban planning and architectural design. This enhanced efficiency can result in cost savings during project development. Moreover, the study's recommendations concerning simulation parameters, such as wind tunnel cell size and refinement levels, offer practical insights for optimizing simulation processes, potentially lowering computational expenses and improving the overall economic viability of urban design projects. To summarize, this research effectively addresses climate-related challenges, benefiting both social well-being and economic efficiency in the field of urban planning and design, while also providing guidance for more efficient simulation-driven design procedures.

Glyptostrobus pensilis (Staunton ex D. Don) K. Koch is a critically endangered species, native to southeastern China and also very locally found in Dak Lak Province, Vietnam. Essential oil isolated from leaves is a monoterpene-rich oil containing mainly limonene (33.3%), α-pinene (23.4%) and bornyl acetate (9.2%). The composition of G. pensilis wood oil is rather complex and the identification of individual components needed fractionation over column chromatography. The main components, identified by GC(RI), GC-MS and 13C NMR, were cedrol (29.3%), occidentalol (6.6%) and occidentalol isomer (5.9%).

Cladanthus mixtus (L.) Chevall., Asteraceae, also known as Moroccan chamomile, is a spontaneous, annual plant growing wild in North-Western Morocco. Economically, the essential oil of C. mixtus is of high interest, Morocco being the only supplier on the international market. Two essential oil samples (EO) were isolated from aerial parts of Cladanthus mixtus (L.) Chevall., and analyzed by a combination of chromatographic and spectroscopic techniques (gas chromatography (GC) in combination with retention indices (RI), gas chromatography-mass spectrometry (GC/MS), and 13C NMR spectroscopy). Computer matching against the in-house 13C NMR library allowed the identification of the eight components at appreciable contents, namely 3,6,6,9-bis-epoxy-farnesa-1,7(14),10-triene, and its 3-epi, 9-epi, and 3,9-diepi epimers, and 6,9-epoxy-farnesa-1,7(14),10-trien-3-ol and its 3-epi, 6-epi, and 3,6-diepi epimers. Our results confirm the tremendous chemical variability of Moroccan C. mixtus essential oil and the usefulness of 13C NMR analysis, in combination with GC(RI), for the identification of uncommon oxygenated sesquiterpenes that induce an original composition.

Aims: Our goal was to study hypothermic cardiac arrest (CA) patients who were not rewarmed by Extracorporeal Life Support (ECLS) but were admitted to a hospital equipped for it. The focus was on whether the decisions of non-rewarming, meaning termination of resuscitation, were compliant with international guidelines based on serum potassium at hospital admission. Methods: We retrospectively included all hypothermic CA who were not rewarmed, from three Swiss centers between 1st January 2000 and 2nd May 2021. Data were extracted from medical charts and assembled into two groups for analysis according to serum potassium. We identified the criteria used to terminate resuscitation. We also retrospectively calculated the HOPE score, a multivariable tool predicting the survival probability in hypothermic CA undergoing ECLS rewarming. Results: Thirty-eight victims were included in the study. The decision of non-rewarming was compliant with international guidelines for 12 (33%) patients. Among the 36 patients for whom the serum potassium was measured at hospital admission, 24 (67%) had a value that – alone – would have indicated ECLS. For 13 of these 24 (54%) patients, the HOPE score was

The essential oils of Oricia suaveolens and Guibourtia ehie from Southern Côte d’Ivoire were extracted by hydrodistillation then analyzed by gas chromatography in combination with retention indices [GC(RI)], gas chromatography coupled with mass spectrometry (GC-MS) and nuclear magnetic resonance of carbone-13 (13C NMR) And described here for the first time. A total of 42 compounds were identified in the essential oils of the leaves of G. ehie while 55, 40 and 23 components were identified in the leaves, stem bark and root bark oils of O. suaveolens, respectively. Essential oils samples were dominated by sesquiterpenes and (E)-β-caryophyllene was the major compound common to all samples: G. ehie leaf oil contained (E)-β-caryophyllene (26.9–40.8%), α-humulene (syn. α-caryophyllene) (6.7–9.7%), β-elemene (5.5–9.5%) and germacrene D (5.6–8.1%); O. suaveolens, leaf oil contained (E)-β-caryophyllene (33.5–39.3%), (E)-β-farnesene (5.9–9,3%), caryophyllene oxide (2.1–7.7%) and α-humulene (4.0–4.6%); stem bark oil contained α-humulene (38.3–45.8%) and (E)-β-caryophyllene (34.7–41.6%); root bark oil contained α-humulene (36.1–47.9%) and (E)-β-caryophyllene (34.3–43.3%). This study highlighted the abundant presence of (E)-β-caryophyllene, a phytocannabinoïd sesquiterpene with countless biological properties, in two plant species: Guibourtia ehie and Oricia suaveolens.

Fatigue affects the capacity of muscles to generate forces and is associated with characteristic changes in EMG signals. It may also influence interjoint and intermuscular coordination. To understand better the global effects of fatigue on multijoint movement, we studied movement kinematics and EMG changes in healthy volunteers asked to hammer repetitively. Movement kinematics and the activity of 20 muscles of the arm, trunk, and leg were recorded before and after subjects became fatigued (as measured using a Borg scale). When fatigue was reached, maximal grip strength and elbow range of motion decreased while the EMG amplitude of the contralateral external oblique muscle was increased. Fatigue did not affect shoulder and wrist kinematics or movement frequency. Results suggest that fatigue influences motion at both local and global levels. Specifically, interjoint and intermuscular coordination adapt to compensate for local effects of fatigue and to maintain key movement characteristics, such as the trajectory of the end effector and the movement frequency. Nonlocal compensations may be a focus of future studies of how fatigue affects complex movements such as those typically performed in the workplace. [ABSTRACT FROM AUTHOR]

Abstract Non-alcoholic fatty liver disease (NAFLD) is the most frequent liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH), which is characterized by triglyceride accumulation, inflammation, and fibrosis. No pharmacological agents are currently approved to treat these conditions, but it is clear now that modulation of lipid synthesis and autophagy are key biological mechanisms that could help reduce or prevent these liver diseases. The folliculin (FLCN) protein has been recently identified as a central regulatory node governing whole body energy homeostasis, and we hypothesized that FLCN regulates highly metabolic tissues like the liver. We thus generated a liver specific Flcn knockout mouse model to study its role in liver disease progression. Using the methionine- and choline-deficient diet to mimic liver fibrosis, we demonstrate that loss of Flcn reduced triglyceride accumulation, fibrosis, and inflammation in mice. In this aggressive liver disease setting, loss of Flcn led to activation of transcription factors TFEB and TFE3 to promote autophagy, promoting the degradation of intracellular lipid stores, ultimately resulting in reduced hepatocellular damage and inflammation. Hence, the activity of FLCN could be a promising target for small molecule drugs to treat liver fibrosis by specifically activating autophagy. Collectively, these results show an unexpected role for Flcn in fatty liver disease progression and highlight new potential treatment strategies.

L’école publique souhaite mettre dans les mains des élèves des ordinateurs, tablettes ou convertibles pour envisager l’éducation numérique. Les compétences d’usages numériques — au sens de maîtrise de l’utilisation — deviennent alors centrales pour permettre à toutes et tous d’apprendre. Mais comment se développent-elles ? Sont-elles transférables d’un outil/environnement à l’autre ? À l’aide d’une revue systématique de la littérature, la transférabilité des compétences d’usages numériques est discutée. Il a été identifié un manque criant de savoirs scientifiques systématiques et fondés sur des résultats empiriques documentant si oui ou non, les compétences d’usages numériques sont transférables et avec quelles médiations. Il semble aujourd’hui impossible de dire avec certitude ce qu’exige le passage d’un outil numérique à l’autre sur le plan des compétences. En l’état, il est difficile d’envisager sereinement les équipements informatiques scolaires.

RationalTo validate a population-based input function (PBIF) model that alleviates the need for scanning since injection time in dynamic whole-body (WBdyn) PET.MethodsThirty-seven patients with suspected/known well-differentiated neuroendocrine tumors were included (GAPETNET trial NTC03576040). All WBdyn 68Ga-DOTATOC-PET/CT acquisitions were performed on a digital PET system (one heart-centered 6 min-step followed by nine WB-passes). The PBIF model was built from 20 image-derived input functions (IDIFs) obtained from a respective number of patients’ WBdyn exams using an automated left-ventricle segmentation tool. All IDIF peaks were aligned to the median time-to-peak, normalized to patient weight and administrated activity, and then fitted to an exponential model function. PBIF was then applied to 17 independent patient studies by scaling it to match the respective IDIF section at 20–55 min post-injection time windows corresponding to WB-passes 3–7. The ratio of area under the curves (AUCs) of IDIFs and PBIF3–7 were compared using a Bland–Altman analysis (mean bias ± SD). The Patlak-estimated mean Ki for physiological uptake (Ki-liver and Ki-spleen) and tumor lesions (Ki-tumor) using either IDIF or PBIF were also compared.ResultsThe mean AUC ratio (PBIF/IDIF) was 0.98 ± 0.06. The mean Ki bias between PBIF3–7 and IDIF was −2.6 ± 6.2% (confidence interval, CI: −5.8; 0.6). For Ki-spleen and Ki-tumor, low relative bias with low SD were found [4.65 ± 7.59% (CI: 0.26; 9.03) and 3.70 ± 8.29% (CI: −1.09; 8.49) respectively]. For Ki-liver analysis, relative bias and SD were slightly higher [7.43 ± 13.13% (CI: −0.15; 15.01)].ConclusionOur study showed that the PBIF approach allows for reduction in WBdyn DOTATOC-PET/CT acquisition times with a minimum gain of 20 min.

Abstract Background Noninvasive ventilation (NIV) is recognized as first line ventilatory support for the management of acute pulmonary edema (APE) and chronic obstructive pulmonary disease (COPD) exacerbations. We aimed to study the prehospital management of patients in acute respiratory distress with an indication for NIV and whether they received it or not. Methods This retrospective study included patients ≥18 years old who were cared for acute respiratory distress in a prehospital setting. Indications for NIV were oxygen saturation (SpO2) 25/min with a presumptive diagnosis of APE or COPD exacerbation. Study population characteristics, initial and at hospital vital signs, presumptive and definitive diagnosis were analyzed. For patients who received NIV, dyspnea level was evaluated with a dyspnea verbal ordinal scale (D-VOS, 0-10) and arterial blood gas (ABG) values were obtained at hospital arrival. Results Among the 187 consecutive patients included in the study, most (n = 105, 56%) had experienced APE or COPD exacerbation, and 56 (30%) received NIV. In comparison with patients without NIV, those treated with NIV had a higher initial RR (35 ± 8/min vs 29 ± 10/min, p

The great genetic and phenotypic diversities characterize the mandarin species (Citrus reticulata). The present study aimed to evaluate a part of this diversity with molecular markers and through the composition of leaf (LEO) and fruit peel (PEO) essential oils. Seventy-two cultivars were chosen for this study to represent some wild and cultivated mandarins growing in the same orchards. The essential oils were analyzed via gas chromatography (retention indices) and via gas chromatography coupled with mass spectrometry. The low similarity of ‘Tachibana’ and ‘Korail tachibana’ with mandarins and other species suggested that they were pure mandarins but were not involved in the genesis of the cultivated forms. This distinction was also evident at the aromatic level with specific compounds or unusual proportions, such as δ-3-carene in PEO or β-phellandrene at 24.9% in ‘Korail tachibana’ LEO. ‘Kunembo’ and ‘Ben di gang ju’ were genetically and chemically identical, with a high proportion of myrcene (>20%) in their LEO. In general, the genetic diversity of SSR markers was higher than the chemical diversity. From the 72 accessions, 54 genotypes were identified, with only 8 aromatic profiles in PEO and 9 in LEO. This diversity of essential oils of mandarins offers new perspectives for the research and validation of new aromatic properties for food and cosmetic purposes.

Seven essential oil samples of two endemic species of Malagasy sage, Salvia sessilifolia Baker and Salvia leucodermis Baker, were investigated via GC(RI), GC-MS and 13C NMR spectrometry. In total, 81compounds were identified accounting for 93.5% to 98.7% of the total composition. The main constituents for the both species were (E)-β-caryophyllene (29.2% to 60.1%), myrcene (1.2% to 21.7%), α-humulene (5.2% to 19.7%), (E)-nerolidol (0.8% to 15.5%) and caryophyllene oxide (1.4% to 10.8%). Ethnobotanical survey of 46 informants revealed that decoctions of leafy twigs and chewed leaves were usually used. Due to the repeated fires, over-harvesting and grazing, the populations of S. sessilifolia and S. leucodermis are drastically fragmented. These risk factors led to threats to the habitats of the target species. Salvia sessilifolia Baker and Salvia leucodermis Baker are proposed to be classified as endangered species.

Abstract Background Emergency medical services regularly encounter severe burns. As standards of care are relatively well-established regarding their hospital management, prehospital care is comparatively poorly defined. The aim of this study was to describe burned patients taken care of by our physician-staffed emergency medical service (PEMS). Methods All patients directly transported by our PEMS to our burn centre between January 2008 and December 2017 were retrospectively enrolled. We specifically addressed three “burn-related” variables: prehospital and hospital burn size estimations, type and volume of infusion and pain assessment and management. We divided patients into two groups for comparison: TBSA

Abstract Background Autoresuscitation describes the return of spontaneous circulation after termination of resuscitation (TOR) following cardiac arrest (CA). We aimed to identify phenomena that may lead to autoresuscitation and to provide guidance to reduce the likelihood of it occurring. Materials and methods We conducted a literature search (Google Scholar, MEDLINE, PubMed) and a scoping review according to PRISMA-ScR guidelines of autoresuscitation cases where patients undergoing CPR recovered circulation spontaneously after TOR with the following criteria: 1) CA from any cause; 2) CPR for any length of time; 3) A point was reached when it was felt that the patient had died; 4) Staff declared the patient dead and stood back. No further interventions took place; 5) Later, vital signs were observed. 6) Vital signs were sustained for more than a few seconds, such that staff had to resume active care. Results Sixty-five patients with ROSC after TOR were identified in 53 articles (1982–2018), 18 (28%) made a full recovery. Conclusions Almost a third made a full recovery after autoresuscitation. The following reasons for and recommendations to avoid autoresuscitation can be proposed: 1) In asystole with no reversible causes, resuscitation efforts should be continued for at least 20 min; 2) CPR should not be abandoned immediately after unsuccessful defibrillation, as transient asystole can occur after defibrillation; 3) Excessive ventilation during CPR may cause hyperinflation and should be avoided; 4) In refractory CA, resuscitation should not be terminated in the presence of any potentially-treatable cardiac rhythm; 5) After TOR, the casualty should be observed continuously and ECG monitored for at least 10 min.

Background. Anaphylaxis is a life-threatening reaction. Its key management is rapid diagnosis and prompt administration of intramuscular epinephrine. There are many barriers to epinephrine use. Objective. To assess the performance of dispatchers at suspecting anaphylaxis, proposing epinephrine treatment, helping find an epinephrine autoinjector (EAI) and using it. Methods. This is a retrospective study. Calls classified as “anaphylaxis” or “allergy” were included, and voice recordings were reviewed. Clinical, environmental, and operational variables were collected. Anaphylaxis was suspected if sudden dyspnoea, abdominal symptoms (vomiting, abdominal pain, or diarrhoea), dizziness, or loss of consciousness were present. Results. The dispatch handled 120,618 dispatch calls. Dispatchers suspected 611 (0.5%) cases of allergy. Among those, 437 (72%) were deemed consistent with anaphylaxis: 65 patients received epinephrine prior to the dispatcher’s advice, and dispatchers proposed the use of an EAI to 141 patients (38%). An EAI was available in 45 situations. The proposition was accepted on 18 cases and performed in 16 cases. The median time from the EAI being in hand and the injection was 50 seconds. Conclusions. Trained dispatchers are able to suspect anaphylaxis, decide when to treat and provide guidance on using an EAI, although their performance can be improved. There is a need for easier access to EAIs in public places.

An experimental procedure using 1H NMR was developed and validated to quantify 5-hydroxymethyl-2(5H)-furanone, a valuable chemical synthon ((S)-enantiomer), in a dichloromethane extract of Helleborus lividus subsp. corsicus leaves. This method, using vanillin as the internal standard, exhibited a perfect linearity of measurements (R2 = 1) associated with very good accuracy (relative errors comprised between −1.62% and 4.25%) and precision (reproducibility 30.51 mg ± 0.4%). The limit of detection and the limit of quantitation have been measured at 0.14 mg and 0.59 mg, respectively. The experiment time is very short since a single analysis is at the minute level. 5-Hydroxymethyl-2(5H)-furanone accounted for nearly 85% in the dichloromethane extract of H. lividus subsp. corsicus leaves (1.7% of the mass of fresh leaves). This plant represents an important and natural source of (S)-5-hydroxymethyl-2(5H)-furanone (main enantiomer; determined using a GC chiral analysis).

Orange (Citrus x aurantium var sinensis) is the most widely consumed citrus fruit, and its essential oil, which is made from the peel, is the most widely used in the food, perfume, and cosmetics industries. This citrus fruit is an interspecific hybrid that would have appeared long before our era and would result from two natural crosses between mandarin and pummelo hybrids. This single initial genotype was multiplied by apomictic reproduction and diversified by mutations to produce hundreds of cultivars selected by men essentially based on phenotypic characteristics of appearance, spread of maturity, and taste. Our study aimed to assess the diversity of essential oil composition and variability in the aroma profile of 43 orange cultivars representing all morphotypes. In agreement with the mutation-based evolution of orange trees, the genetic variability tested with 10 SSR genetic markers was null. The oils from peels and leaves extracted by hydrodistillation were analyzed for composition by GC (FID) and GC/MS and for aroma profile by the CATA (Check All That Apply) method by panelists. Oil yield varied between varieties by a factor of 3 for PEO and a factor of 14 for LEO between maximum and minimum. The composition of the oils was very similar between cultivars and was mainly dominated by limonene (>90%). However, small variations were observed as well as in the aromatic profile, with some varieties clearly distinguishing themselves from the others. This low chemical diversity contrasts with the pomological diversity, suggesting that aromatic variability has never been a selection criterion in orange trees.

Abstract The 5A score predicts in-hospital mortality of patients suffering from accidental hypothermia, including those not in cardiac arrest. The HOPE score was specifically developed to predict survival for the subgroup of hypothermic patients in cardiac considered for extracorporeal life support rewarming. The C-statistic in the external validation study of the HOPE score was 0.825 (95% CI: 0.753–0.897), confirming its excellent discrimination. In addition, its good calibration allows for a reliable interpretation of the corresponding survival probability after rewarming. The HOPE score should be used for predicting outcome and selecting hypothermic patients in cardiac arrest for rewarming.

BACKGROUND: Rapid access to a trauma centre for severely injured road accident victims, conceptualised as the Golden Hour, links access time to definitive treatment within 1 hour of trauma with reduced risks of morbidity and mortality. Access times have not been studied in Switzerland. The aim of this work was to model the transport time by ambulance of seriously injured road traffic accident victims to one of the 12 trauma centres in Switzerland and to investigate whether this time influenced mortality. METHODS: Isochronous travel curves in 10-minute increments were modelled around each of the 12 Swiss trauma centres to assess travel times at the Swiss national level, based on the shortest travel time from the location of a serious road accident to the nearest trauma centre. We used the national database of the Federal Roads Office, which provided the geolocation of these accidents occurring between 2011 and 2017. The association between mortality and transport time to the nearest trauma centre was then analysed. RESULTS: The current distribution of trauma centres allowed access time within the Golden Hour for accidents occurring on the Swiss plateau, but the time was more prolonged in the Alps or the Jura. An association existed between mortality and prehospital transport time from the site of an accident to the nearest trauma centre. For each additional 10-minute isochrone, an average increase of 0.4% in mortality was observed. CONCLUSION: This work showed an adequate distribution of trauma centres in Switzerland and suggests a positive relationship between transport time to the nearest trauma centre and mortality. The numerous confounding factors not systematically collected in publicly available databases limit the robustness of our results. This study confirms the importance of having a national trauma registry to allow quality analyses to guide public health decisions.

Aim: Patients with hypothermic cardiac arrest may survive with an excellent outcome after extracorporeal life support rewarming (ECLSR). The HOPE (Hypothermia Outcome Prediction after ECLS) score is recommended to guide the in-hospital decision on whether or not to initiate ECLSR in patients in cardiac arrest following accidental hypothermia. We aimed to assess the HOPE-estimated survival probabilities for a set of survivors of hypothermic cardiac arrest who had extreme values for the variables included in the HOPE score. Methods: Survivors were identified and selected through a systematic literature review including case reports. We calculated the HOPE score for each patient who presented extraordinary clinical parameters. Results: We identified 12 such survivors. The HOPE-estimated survival probability was ≥10% for all (n = 11) patients for whom we were able to calculate the HOPE score. Conclusion: Our study confirms the robustness of the HOPE score for outliers and thus further confirms its external validity. These cases also confirm that hypothermic cardiac arrest is a fundamentally different entity than normothermic cardiac arrest. Using HOPE for extreme cases may support the proper calibration of a clinician’s prognosis and therapeutic decision based on the survival chances of patients with accidental hypothermic cardiac arrest.

Abstract Background Hip fracture causes moderate to severe pain and while fascia iliaca block has been reported to provide analgesic benefit, most previous trials were unblinded, with subsequent high risks of performance, selection and detection biases. In this randomized, control double-blind trial, we tested the hypothesis that a fascia iliaca block provides effective analgesia for patients suffering from hip fracture. Methods Thirty ASA I-III hip fracture patients over 70 years old, who received prehospital morphine, were randomized to receive either a fascia iliaca block using 30 ml of bupivacaine 0.5% with epinephrine 1:200,000 or a sham injection with normal saline. The fascia iliaca block was administered by emergency medicine physicians trained to perform an anatomic landmark-based technique. The primary outcome was the comparison between groups of the longitudinal pain score profiles at rest over the first 45 min following the procedure (numeric rating scale, 0–10). Secondary outcomes included the longitudinal pain score profiles on movement and the comparison over 4 h, 8 h, 12 h, and 24 h after the procedure, along with cumulative intravenous morphine consumption at 24 h. Results At baseline, the fascia iliaca group had a lower mean pain score than the sham injection group, both at rest (difference = − 0.9, 95%CI [− 2.4, 0.5]) and on movement (difference = − 0.9, 95%CI [− 2.7; 0.9]). These differences remained 45 min after the procedure and the two longitudinal pain score profiles were parallel both for patients at rest and on movement (test of parallelism for patients at rest p = 0.53 and on movement p = 0.45). The same parallel change in pain scores over time was observed over 24 h of follow-up (test of parallelism for patients at rest p = 0.82 and on movement p = 0.12). These results were confirmed after adjustment for gender, ASA score, and cumulative sums of intravenous morphine received pre-procedure and during-follow-up. In addition, there was no difference between the two groups in total cumulative intravenous morphine consumption at 24 h. Conclusion Fascia iliaca block following anatomic landmarks may not provide supplementary analgesia for patients suffering from hip fracture, when low pain scores are reported after prehospital morphine. Additional larger trials will help reach definitive conclusion. Trial registration number Clinicaltrials.gov – NCT02433548. The study was registered retrospectively.

The variability of chemical composition of the leaf essential oil (EO) from Neuropeltis acuminata, a climbing liana growing wild in Ivory Coast, was investigated for the first time. The in vitro anti-inflammatory activity was also evaluated. Thirty oil samples were isolated from leaves collected in three forests of the country and analyzed using a combination of Column Chromatography (CC), Gas Chromatography with Retention Indices (GC(FID)), Gas Chromatography-Mass Spectrometry (GC-MS), and 13Carbon-Nuclear Magnetic Resonance (13C-NMR). Fractionation by CC led to the first-time isolation from natural source of δ-cadinen-11-ol, whose structural elucidation by one dimension (1D) and 2D-NMR spectroscopy is reported here. Finally, 103 constituents accounting for 95.7 to 99.6% of the samples’ compositions were identified. As significant variations of the major constituents were observed, the 30 oil compositions were submitted to hierarchical cluster and principal components analyses. Five distinct groups were evidenced: Group I, dominated by (E)-β-caryophyllene, kessane, and δ-cadinene, while the main constituents of Group II were germacrene B, ledol, α-humulene, (E)-γ-bisabolen-12-ol, and γ-elemene. Group III exhibited guaiol, germacrene D, atractylone, (E)-γ-bisabolen-12-ol, δ-cadinene and bulnesol as main compounds. Group IV was dominated by (E)-nerolidol, guaiol, selina-4(15),7(11)-diene and bulnesol, whereas (E)-β-caryophyllene, α-humulene and α-muurolene were the prevalent compounds of Group V. As the harvest took place in the same dry season in the three forests, the observed chemical variability could be related to harvest sites, which includes climatic and pedologic factors, although genetic factors could not be excluded. The leaf oil sample S24 behaved as a high inhibitor of LipOXygenase (LOX) activity (half maximum Inhibitory Concentration, IC50: 0.059 ± 0.001 mg mL−1), suggesting an anti-inflammatory potential.

Besides skeletal muscle dysfunction, Duchenne muscular dystrophy (DMD) exhibits a progressive cardiomyopathy characterized by an impaired calcium (Ca2+) homeostasis and a mitochondrial dysfunction. Here we aimed to determine whether sarco-endoplasmic reticulum (SR/ER)–mitochondria interactions and mitochondrial function were impaired in dystrophic heart at the early stage of the pathology. For this purpose, ventricular cardiomyocytes and mitochondria were isolated from 3-month-old dystrophin-deficient mice (mdx mice). The number of contacts points between the SR/ER Ca2+ release channels (IP3R1) and the porine of the outer membrane of the mitochondria, VDAC1, measured using in situ proximity ligation assay, was greater in mdx cardiomyocytes. Expression levels of IP3R1 as well as the mitochondrial Ca2+ uniporter (MCU) and its regulated subunit, MICU1, were also increased in mdx heart. MICU2 expression was however unchanged. Furthermore, the mitochondrial Ca2+ uptake kinetics and the mitochondrial Ca2+ content were significantly increased. Meanwhile, the Ca2+-dependent pyruvate dehydrogenase phosphorylation was reduced, and its activity significantly increased. In Ca2+-free conditions, pyruvate-driven complex I respiration was decreased whereas in the presence of Ca2+, complex I-mediated respiration was boosted. Further, impaired complex I-mediated respiration was independent of its intrinsic activity or expression, which remains unchanged but is accompanied by an increase in mitochondrial reactive oxygen species production. Finally, mdx mice were treated with the complex I modulator metformin for 1 month. Metformin normalized the SR/ER-mitochondria interaction, decreased MICU1 expression and mitochondrial Ca2+ content, and enhanced complex I-driven respiration. In summary, before any sign of dilated cardiomyopathy, the DMD heart displays an aberrant SR/ER-mitochondria coupling with an increase mitochondrial Ca2+ homeostasis and a complex I dysfunction. Such remodeling could be reversed by metformin providing a novel therapeutic perspective in DMD.

Loudness is the magnitude of the auditory sensation that a listener experiences when exposed to a sound. Several sound attributes are reported to affect loudness, such as the sound pressure level at the listener's ears and the spectral content. In addition to these physical attributes of the stimulus, some subjective attributes also appear to affect loudness. When presented with a sound, a listener interacts with an auditory object and can focus on several aspects of the latter. Loudness appears to differ depending on how listeners apprehend this object, notably whether they focus on the sound that reaches their ears or that is produced by the source. The way listeners focus on the auditory object may depend on the stimulus itself. For instance, they might be more likely to focus on the sound emitted by the source if the latter is visible. The instructions given by the experimenters can also explicitly direct the listener's focus on the sound reaching the ears or emitted by the source. The present review aims at understanding how listeners focus on the auditory object depending on the stimuli and instructions they are provided with, and to describe how loudness depends on this focus.

As the world is severely affected by COVID-19 pandemic, the use of chloroquine and hydroxychloroquine in prevention or for the treatment of patients is allowed in multiple countries but remained at the center of much controversy in recent days. This review describes the properties of chloroquine and hydroxychloroquine, and highlights not only their anti-viral effects but also their important immune-modulatory properties and their well-known use in autoimmune diseases, including systemic lupus and arthritis. Chloroquine appears to inhibit in vitro SARS virus' replication and to interfere with SARS-CoV2 receptor (ACE2). Chloroquine and hydroxychloroquine impede lysosomal activity and autophagy, leading to a decrease of antigen processing and presentation. They are also known to interfere with endosomal Toll-like receptors signaling and cytosolic sensors of nucleic acids, which result in a decreased cellular activation and thereby a lower type I interferons and inflammatory cytokine secretion. Given the antiviral and anti-inflammatory properties of chloroquine and hydroxychloroquine, there is a rational to use them against SARS-CoV2 infection. However, the anti-interferon properties of these molecules might be detrimental, and impaired host immune responses against the virus. This duality could explain the discrepancy with the recently published studies on CQ/HCQ treatment efficacy in COVID-19 patients. Moreover, although these treatments could be an interesting potential strategy to limit progression toward uncontrolled inflammation, they do not appear per se sufficiently potent to control the whole inflammatory process in COVID-19, and more targeted and/or potent therapies should be required at least in add-on.

Background. The use of lights and siren transport (LST) has been a matter of debate because of the short time savings and well-established increased risks for Emergency Medical Services (EMS) and bystanders. Time-critical hospital intervention (TCHI) denotes urgently needed procedures that cannot be performed properly in an out-of-hospital setting. Since 2013, rapid transportation from the field, fast-track, is currently used for patients with acute ST-elevation myocardial infarction, suspicion of acute stroke and out-of-hospital cardiac arrest. The aim of this study was to determine whether the use of LST was associated with the realization of TCHI for nontrauma cases within 15 minutes of hospital arrival, to quantify overtriage (LST without TCHI) and to identify the predictors of TCHI. Methods. This is a monocentric prospective observational study of nontrauma patients transported by ambulance. Based on Ross et al.’s work in 2016 on trauma patients, TCHI procedures were developed by the study team. Descriptive statistics were used to determine whether the use of LST was associated with the realization of TCHI. Multivariable analyses determined the predictors of TCHI and compared clinical outcomes. Results. On the 324 patients included, 67 (20.7%) benefitted from LST, with 40 (59.7%) receiving TCHI (p

Rootstock is widely used for the cultivation of citrus fruits because it brings resistance or tolerance to diseases or environmental constrains and modulates the fruit quality. Polyploidization is a widespread improvement strategy in citrus. The objective was to evaluate the effect of rootstock and ploidy level on the composition of essential oils. Two trials were conducted, one displaying a ‘Navelina’ orange grafted on three rootstocks and a second combining two ploidy levels (di and tetraploid) of scion (‘Pineapple’ orange) and rootstock (‘Carrizo’ citrange). The composition of peel essential oil (PEO) was analyzed by gas chromatography coupled with mass spectrometry, and a panel of experts analyzed its flavor variation with a triangle test approach. The rootstock influenced the yield and composition of the orange PEO, with a low impact on flavor. Neither the rootstock nor the scion ploidy level affected the PEO yield. Only the tetraploid level of the scion significantly modified the PEO composition, reducing the oxygenated compound fraction. Sensitive significant differences were detected between the reference sample (diploid scion–diploid rootstock) and the three other combinations. These results suggest that for the profiling of an aromatic flavor, the rootstock is a key element as is the ploidy level of the scion.

Abstract Background Avalanche rescues mostly rely on helicopter emergency medical services (HEMS) and include technical rescue and complex medical situations under difficult conditions. The adequacy of avalanche victim management has been shown to be unexpectedly low, suggesting the need for quality improvement. We analyse the technical rescue and medical competency requirements of HEMS crewmembers for avalanche rescue missions, as well as their clinical exposure. The study aims to identify areas that should be the focus of future quality improvement efforts. Methods This 15-year retrospective study of avalanche rescue by the Swiss HEMS Rega includes all missions where at least one patient had been caught by an avalanche, found within 24 h of the alarm being raised, and transported. Results Our analyses included 422 missions (596 patients). Crews were frequently confronted with technical rescue aspects, including winching (29%) and patient location and extrication (48%), as well as multiple casualty accidents (32%). Forty-seven percent of the patients suffered potential or overt vital threat; 29% were in cardiac arrest. The on-site medical management of the victims required a large array of basic and advanced medical skills. Clinical exposure was low, as 56% of the physicians were involved in only one avalanche rescue mission over the study period. Conclusions Our data provide a solid baseline measure and valuable starting point for improving our understanding of the challenges encountered during avalanche rescue missions. We further suggest QI interventions, that might be immediately useful for HEMS operating under similar settings. A coordinated approach using a consensus process to determine quality indicators and a minimal dataset for the specific setting of avalanche rescue would be the logical next step.

Abstract Background Helicopter emergency medical services (HEMS) are popular rescue systems despite inconsistent evidence in the scientific literature to support their use for primary interventions, as well as for inter-facility transfer (IFT). There is little research about IFT by HEMS, hence questions remain about the appropriateness of this method of transport. The aim of this study was to describe a case-mix of operational and medical characteristics for IFT activity of a sole HEMS base, and identify indicators of over-triage. Methods This is a retrospective study on HEMS IFT over 36 months, from January 1st 2013 to December 31st 2015. Medical and operational data from the database of the Emergency Department of Lausanne University Hospital, which provides the emergency physicians for this helicopter base, were reviewed. It included distance and time of flight transport, type of care during flight, and estimated distance of transport if conducted by ground. Results There were 2194 HEMS missions including 979 IFT (44.6%). Most transfers involved adults (> 17 years old; 799 patients, 81.6%). Forty patients (4.1%) were classified as having benefitted from resuscitation or life-saving measures performed in flight, 615 (62.8%) from emergency treatment and 324 (33.1%) from simple clinical examination. The median distance by air between hospitals was 35.4 km. The estimated median distance by road was 47.7 km. The median duration time from origin to destination by air was 12 min. Conclusions This case-mix of IFTs by HEMS presents a high severity. There are many signs in favour of over-triage. We propose indicators to help choosing whether HEMS is the most appropriate mean of transport to perform the transfer regarding patient condition, geography, and medical competences available aboard ground ambulances; this may reduce over-triage.

The chemical variability and the in vitro anti-inflammatory activity of the leaf essential oil from Ivorian Isolona dewevrei were investigated for the first time. Forty-seven oil samples were analyzed using a combination of CC, GC(RI), GC-MS and 13C-NMR, thus leading to the identification of 113 constituents (90.8–98.9%). As the main components varied drastically from sample to sample, the 47 oil compositions were submitted to hierarchical cluster and principal components analyses. Three distinct groups, each divided into two subgroups, were evidenced. Subgroup I−A was dominated by (Z)-β-ocimene, β-eudesmol, germacrene D and (E)-β-ocimene, while (10βH)-1β,8β-oxido-cadina-4-ene, santalenone, trans-α-bergamotene and trans-β-bergamotene were the main compounds of Subgroup I−B. The prevalent constituents of Subgroup II−A were germacrene B, (E)-β-caryophyllene, (5αH,10βMe)-6,12-oxido-elema-1,3,6,11(12)-tetraene and γ-elemene. Subgroup II−B displayed germacrene B, germacrene D and (Z)-β-ocimene as the majority compounds. Germacrene D was the most abundant constituent of Group III, followed in Subgroup III−A by (E)-β-caryophyllene, (10βH)-1β,8β-oxido-cadina-4-ene, germacrene D-8-one, and then in Subgroup III−B by (Z)-β-ocimene and (E)-β-ocimene. The observed qualitative and quantitative chemical variability was probably due to combined factors, mostly phenology and season, then harvest site to a lesser extent. The lipoxygenase inhibition by a leaf oil sample was also evaluated. The oil IC50 (0.020 ± 0.005 mg/mL) was slightly higher than the non-competitive lipoxygenase inhibitor NDGA IC50 (0.013 ± 0.003 mg/mL), suggesting a significant in vitro anti-inflammatory potential.

Abstract Background Pelvic fractures are severe injuries with frequently associated multi-system trauma and a high mortality rate. The value of the pelvic fracture pattern for predicting transfusion requirements and mortality is not entirely clear. To address hemorrhage from pelvic injuries, the early application of pelvic binders is now recommended and arterial angio-embolization is widely used for controlling arterial bleeding. Our aim was to assess the association of the pelvic fracture pattern according to the Tile classification system with transfusion requirements and mortality rates, and to evaluate the correlation between the use of pelvic binders and arterial angio-embolization and the mortality of patients with pelvic fractures. Methods Single-center retrospective cohort study including all consecutive patients with a pelvic fracture from January 2008 to June 2015. All radiological fracture patterns were independently reviewed and grouped according to the Tile classification system. Data on patient demographics, use of pelvic binders and arterial angio-embolization, transfusion requirements and mortality were extracted from the institutional trauma registry and analyzed. Results The present study included 228 patients. Median patient age was 43.5 years and 68.9% were male. The two independent observers identified 105 Tile C (46.1%), 71 Tile B (31.1%) and 52 Tile A (22.8%) fractures, with substantial to almost perfect interobserver agreement (Kappa 0.70-0.83). Tile C fractures were associated with a higher mortality rate (p = 0.001) and higher transfusion requirements (p

Abstract Opening of the mitochondrial permeability transition pore (mPTP) plays a major role in cell death during cardiac ischaemia-reperfusion. Adult isolated rodent cardiomyocytes are valuable cells to study the effect of drugs targeting mPTP. This study investigated whether the use of Ca2+ ionophores (A23187, ionomycin and ETH129) represent a reliable model to study inhibition of mPTP opening in cardiomyocytes. We monitored mPTP opening using the calcein/cobalt fluorescence technique in adult rat and wild type or cyclophilin D (CypD) knock-out mice cardiomyocytes. Cells were either treated with Ca2+ ionophores or subjected to hypoxia followed by reoxygenation. The ionophores induced mPTP-dependent swelling in isolated mitochondria. A23187, but not ionomycin, induced a decrease in calcein fluorescence. This loss could not be inhibited by CypD deletion and was explained by a direct interaction between A23187 and cobalt. ETH129 caused calcein loss, mitochondrial depolarization and cell death but CypD deletion did not alleviate these effects. In the hypoxia-reoxygenation model, CypD deletion delayed both mPTP opening and cell death occurring at the time of reoxygenation. Thus, Ca2+ ionophores are not suitable to induce CypD-dependent mPTP opening in adult murine cardiomyocytes. Hypoxia-reoxygenation conditions appear therefore as the most reliable model to investigate mPTP opening in these cells.

Summary: TFEB and TFE3 are transcriptional regulators of the innate immune response, but the mechanisms regulating their activation upon pathogen infection are poorly elucidated. Using C. elegans and mammalian models, we report that the master metabolic modulator 5′-AMP-activated protein kinase (AMPK) and its negative regulator Folliculin (FLCN) act upstream of TFEB/TFE3 in the innate immune response, independently of the mTORC1 signaling pathway. In nematodes, loss of FLCN or overexpression of AMPK confers pathogen resistance via activation of TFEB/TFE3-dependent antimicrobial genes, whereas ablation of total AMPK activity abolishes this phenotype. Similarly, in mammalian cells, loss of FLCN or pharmacological activation of AMPK induces TFEB/TFE3-dependent pro-inflammatory cytokine expression. Importantly, a rapid reduction in cellular ATP levels in murine macrophages is observed upon lipopolysaccharide (LPS) treatment accompanied by an acute AMPK activation and TFEB nuclear localization. These results uncover an ancient, highly conserved, and pharmacologically actionable mechanism coupling energy status with innate immunity. : El-Houjeiri et al. show that loss of FLCN or pharmacological activation of AMPK induces TFEB/TFE3-dependent pro-inflammatory cytokine expression and phagocytosis in macrophages and confers pathogen resistance in C. elegans. These results uncover an ancient, highly conserved, and pharmacologically actionable mechanism coupling energy status to innate immunity. Keywords: TFEB, TFE3, FLCN, AMPK, innate immune response, pathogen resistance, autophagy, lysosomal biogenesis, phagocytosis

Sour oranges (Citrus aurantium L.) are well known in the processing and cosmetics industries for the aromatic properties of their essential oils. Intercultivar genetic and aromatic diversity is not well documented. The objective of this study was to evaluate the impact of morphological selection and genetic mechanisms of varietal diversification (mutation or hybridization) on the aromatic and odor variability of sour orange essential oils. Forty-five sour orange accessions from INRAE-CIRAD citrus Biological Resources Center (France) were assessed for ten simple sequence repeat (SSR) and 54 single nucleotide polymorphism (SNP) markers, nine morphochemical fruit traits and with the aromatic components of leaf and peel essential oils. Thirty-nine sour oranges displayed no intercultivar molecular polymorphism and six genotypes originated from interspecific hybridizations involving sour orange, citron, pummelo or mandarin. The peel essential oil (PEO) diversity was low, in accordance with the genetic diversity. The predominance of limonene (>90%) prevents any possible correlation to be made between the composition and the variation in sensory profiles detected by panelists. Few compounds in the leaf essential oil (LEO), such as linalool, linalyl acetate, α-terpineol and geraniol were significantly different across sour oranges varieties. The morphological fruit attributes mainly used in varietal selection differed highly across the main genetically identical group of sour orange accessions. These results confirm that mutation can generate variability in aromatic compounds and aromas and that their exploitation requires an improvement in characterization processes.

The Papeda Citrus subgenus includes several species belonging to two genetically distinct groups, containing mostly little-exploited wild forms of citrus. However, little is known about the potentially large and novel aromatic diversity contained in these wild citruses. In this study, we characterized and compared the essential oils obtained from peels and leaves from representatives of both Papeda groups, and three related hybrids. Using a combination of GC, GC-MS, and 13C-NMR spectrometry, we identified a total of 60 compounds in peel oils (PO), and 76 compounds in leaf oils (LO). Limonene was the major component in almost all citrus PO, except for C. micrantha and C. hystrix, where β-pinene dominated (around 35%). LO composition was more variable, with different major compounds among almost all samples, except for two citrus pairs: C. micrantha/C. hystrix and two accessions of C. ichangensis. In hybrid relatives, the profiles were largely consistent with their Citrus/Papeda parental lineage. This high chemical diversity, not only among the sections of the subgenus Papeda, but also between species and even at the intraspecific level, suggests that Papeda may be an important source of aroma diversity for future experimental crosses with field crop species.

The cosmetic and fragrance industry largely exploits citrus essential oils (EOs) because of their aromatic properties. EO compositions are complex and differ between fruit pericarp (PEO) and leaf (LEO). Citrus fruit grow in many countries under very different climates. Seventeen citrus cultivars were selected and their similarities between the two collections were verified by SSR (Single Sequence Repeat) and InDel (Insertion and Deletion) markers to assess the effects of the environment and cultivation practices on the EO yield and composition. LEOs and PEOs were extracted by water distillation and analyzed by GC-MS. PEO yields were generally higher in Corsica than in Bahia, especially in the citron family. PEOs in this family were richer in limonene in Bahia than in Corsica while, conversely, neral, geranial and derivatives were present in a higher proportion in Corsican varieties. A few minor components were site-specific, such as nookaton, a pummelo-specific compound that was not present in grapefruit cultivated in Bahia. If climate change over the last 20 years has not affected the PEO composition in Corsica, the contrasted environmental conditions and cultural practices between Bahia and Corsica could possibly explain the EO variations.

Three new compounds, a dihydrobenzofuran (coumaran) derivative (compound 1) and two pterocarpans (compounds 2 and 3) were isolated from a root extract of Calicotome villosa growing wild in Corsica. Their structures were elucidated using 1D and 2D NMR spectroscopy and MS/MS as 2-(1-methylethenyl)-5-hydroxy-6-carbomethoxy-2,3-dihydro-benzofuran, 4,9-dihydroxy-3-methoxy-2-dimethylallylpterocarpan, and 4,9-dihydroxy-3′,3′-dimethyl-2,3-pyranopterocarpan.

The essential oils of six endemic Malagasy Helichrysum species were investigated by GC (RI), GC−MS and 13C NMR spectrometry. In total, 153 compounds were identified accounting for 90.8% to 99.9% of the total composition. The main constituents were α-pinene for H. benthamii, 1,8-cineole for H. dubardii, (E)-β-caryophyllene for H. indutum, and H. bojerianum. H. diotoides essential oil was characterized by the presence of two lilac alcohols and four lilac acetates whereas H. hirtum essential oil exhibited an atypical composition with 7β-H-silphiperfol-5-ene, 7-epi-subergorgiol, and 7-epi-silphiperfol-5-en-13-oic acid as major components.

Along the entire lifetime, Notch is actively involved in dynamic changes in the cellular architecture and function of the nervous system. It controls neurogenesis, the growth of axons and dendrites, synaptic plasticity, and ultimately neuronal death. The specific roles of Notch in adult brain plasticity and neurological disorders have begun to be unraveled in recent years, and pieces of experimental evidence suggest that Notch is operative in diverse brain pathologies including tumorigenesis, stroke, and neurological disorders such as Alzheimer’s disease, Down syndrome, and multiple sclerosis. In this review, we will cover the recent findings of Notch signaling and neural dysfunction in adult human brain and discuss its relevance in the pathogenesis of diseases of the central nervous system.

Expression of the CC chemokine receptor 1 (CCR1) by tumor cells has been associated with protumoral activity; however, its role in nontumoral cells during tumor development remains elusive. Here, we investigated the role of CCR1 deletion on stromal and hematopoietic cells in a liver metastasis tumor model. Metastasis development was strongly impaired in CCR1-deficient mice compared to control mice and was associated with reduced liver monocyte infiltration. To decipher the role of myeloid cells, sublethally irradiated mice were reconstituted with CCR1-deficient bone marrow (BM) and showed better survival rates than the control reconstituted mice. These results point toward the involvement of CCR1 myeloid cell infiltration in the promotion of tumor burden. In addition, survival rates were extended in CCR1-deficient mice receiving either control or CCR1-deficient BM, indicating that host CCR1 expression on nonhematopoietic cells also supports tumor growth. Finally, we found defective tumor-induced neoangiogenesis (in vitro and in vivo) in CCR1-deficient mice. Overall, our results indicate that CCR1 expression by both hematopoietic and nonhematopoietic cells favors tumor aggressiveness. We propose CCR1 as a potential therapeutical target for liver metastasis therapy.

Pulse pressure variation can predict fluid responsiveness in strict applicability conditions. The purpose of this study was to describe the clinical applicability of pulse pressure variation during episodes of patient hemodynamic instability in the intensive care unit. We conducted a five-day, seven-center prospective study that included patients presenting with an unstable hemodynamic event. The six predefined inclusion criteria for pulse pressure variation applicability were as follows: mechanical ventilation, tidal volume >7 mL/kg, sinus rhythm, no spontaneous breath, heart rate/respiratory rate ratio >3.6, absence of right ventricular dysfunction, or severe valvulopathy. Seventy-three patients presented at least one unstable hemodynamic event, with a total of 163 unstable hemodynamic events. The six predefined criteria for the applicability of pulse pressure variation were completely present in only 7% of these. This data indicates that PPV should only be used alongside a strong understanding of the relevant physiology and applicability criteria. Although these exclusion criteria appear to be profound, they likely represent an absolute contraindication of use for only a minority of critical care patients.