The first quick olfactory test specific for Alzheimer's disease and French culture.

PURPOSE: Olfactory identification disorder is considered a promising early biomarker of Alzheimer's disease (AD). The QUICK TODA2 can be used as a short olfactory screening tool specific for French AD patients. The selection of AD specific odorants and the design of this screening were the main objectives of this twofold study. METHODS: In study 1, the TODA2 olfactory test was administered to 43 mild-AD patients and 45 healthy controls (HC) in five memory centres in France. The selection of AD specific odorants was based on the differences in the proportion of correct answers and in the threshold means between AD and HC groups. In study 2, another set of 19 mild-AD patient were included at the memory centre of Nice Hospital. All participants completed the olfactory assessment pipeline including the QUICK TODA2, TODA2 and Sniffin' Sticks Identification sub-Test (SST-i). The individual scores of the three tests were correlated. RESULTS: In study 1, ten TODA2 odorants could significantly differentiate AD participants from controls. We selected the six most AD-sensitive items to design the QUICK TODA2. In study 2, we reported strong significant correlations between QUICK TODA2 and TODA2 (ρ(17) = 0.68, p = 0.001**), SST-i and QUICK TODA2 (ρ(17) = 0.65, p = 0.002**), SST-i and TODA2 (ρ(17) = 0.57, p = 0.01*). CONCLUSION:  QUICK TODA2 is a 5-min non-invasive olfactory AD screening tool dedicated to French culture. Its results converge with those of longer, validated olfactory tests. It could be used as a quick screening tool in the general daily practice before an extensive assessment in memory centres.

Chemical Composition and Antiplasmodial Activity of the Essential Oil of Rhododendron subarcticum Leaves from Nunavik, Québec, Canada.

Dwarf Labrador tea, Rhododendron subarcticum Harmaja, is a popular medicinal plant in use by First Nations of Northern Canada, but its phytochemistry has remained largely unexplored. We have isolated and characterized the essential oil from a population of this species harvested near the treeline in Nunavik, Québec. Analyses by gas chromatography-mass spectrometry (GC-MS) and gas chromatography/flame-ionization detection (GC/FID) led to the identification of 53 compounds; the main secondary metabolites were ascaridole (64.7% of the total FID area) and p-cymene (21.1%). Such a composition resembles a chemotype observed for R. tomentosum, a close relative found mainly in Europe and Asia, but has never been attributed to R. subarcticum. Growth inhibition assays against different strains of Plasmodium falciparum (3D7, Dd2), the parasite responsible for the most severe form of malaria, were conducted with either the R. subarcticum's essential oil or the isolated ascaridole. Our results show that the essential oil's biological activity can be attributed to ascaridole as its IC50 is more than twice that of ascaridole [ascaridole's IC50 values are 147.3 nM (3D7) and 104.9 nM (Dd2)].

Commiphora wildii Merxm. Essential Oil: Natural Heptane Source and Co-Product Valorization.

As an alternative to fossil volatile hydrocarbon solvents used nowadays in perfumery, investigation on essential oil of Commiphora wildii Merxm. oleo gum resin as a source of heptane is reported here. Heptane, representing up to 30 wt-% of this oleo gum resin, was successfully isolated from the C. wildii essential oil, using an innovative double distillation process. Isolated heptane was then used as a solvent in order to extract some noble plants of perfumery. It was found that extracts obtained with this solvent were more promising in terms of sensory analysis than those obtained from fossil-based heptane. In addition, in order to valorize the essential oil depleted from heptane, chemical composition of this oil was found to obtain, and potential biological activity properties were studied. A total of 172 different compounds were identified by GC-MS in the remaining oil. In vitro tests-including hyaluronidase, tyrosinase, antioxidant, elastase and lipoxygenase, as well as inhibitory tests against two yeasts and 21 bacterial strains commonly found on the skin-were carried out. Overall, bioassays results suggest this heptane-depleted essential oil is a promising active ingredient for cosmetic applications.

Sustainable extraction of antioxidants from out-of-caliber kiwifruits.

Valorisation of discarded kiwifruits is proposed by extracting bioactive compounds using sustainable solvents namely deep eutectic solvents (DES). A screening of fifteen DES and several hydrogen bonding donor solvents was carried out. Extraction efficiency was measured in terms of antioxidant activity using DPPH and FRAP tests. The influence of solvents characteristics in particular DES structure, presence of ethanol or water, and pH of DES/water mixture on the antioxidant properties of the extracts was studied. Results show that kiwi peels extracts obtained with DES based on carboxylic acids exhibit enhanced antioxidant activity compared to conventional solvents and alcohol-based DES with a maximum DPPH scavenging activity of 42.0 mg TE/g DW. Glycerol or ethylene glycol are also efficient at extracting antioxidant compounds with DPPH scavenging activity of 33.1 and 36.7 mg TE/g DW. Finally, a chemical analysis of extracts using HPTLC revealed that most active compounds extracted are polyphenolic compounds, presumably tannins.

What about using sniffin' sticks 12 items test to screen post-COVID-19 olfactory disorders?

BACKGROUND: Post-COVID-19 Olfactory impairment has a negative impact on quality of life. The Sniffin Sticks test 12 items (SST-12) can be used in quick olfactory disorders screening. Its evaluation in a post-covid-19 situation was the main objective of this work. METHODS: All patient impaired with a post-COVID olfactory loss were included while consulting to the ENT department. The clinical examination included an olfaction recovery self-assessment (VAS), a nasofibroscopy, a quality of life (QoL) assessment, the complete Sniffin' Sticks Test (SST), and the SST-12. RESULTS: Among the 54 patients included, 92% (n = 50) were correctly screened as olfactory impaired by SST-12. We report excellent correlations between SST-12 and SST (rho (52) = 0.98, p < 0.001), QoL(rho(52) = 0.33 p = 0.016), or VAS (rho(52) = 0.49, p < 0.001) assessments. CONCLUSIONS: SST-12 is a quick and reliable tool to screen large-scale population of post-COVID-19 olfactory impaired patients and could be used in a general daily clinical practice.

Solvent-Free Microwave Extraction of Thymus mastichina Essential Oil: Influence on Their Chemical Composition and on the Antioxidant and Antimicrobial Activities.

Solvent-free microwave extraction (SFME) is a combination of microwave heating and dry distillation performed at atmospheric pressure without the addition of water or organic solvents that has been proposed as a green method for the extraction of essential oils from aromatic and medicinal herbs. In this work, SFME and the conventional techniques of steam distillation (SD) and hydrodistillation (HD) were compared with respect to the extraction and antioxidant and antimicrobial activities of Thymus mastichina essential oil. The main constituent of essential oils obtained using different methods was 1,8-cineole (eucalyptol). The results showed that the essential oils extracted by means of SFME in 30 min were quantitatively (yield) and qualitatively (aromatic profile) similar to those obtained using conventional HD over 120 min. In addition, SFME generates less waste and less solvent, consumes less energy, and provides a higher yield for a shorter extraction time, which is advantageous for the extraction of the T. mastichina essential oil compared to SD. The antioxidant and antimicrobial activities of the T. mastichina essential oil obtained from either SFME or conventional extraction methods (SD or HD) showed a similar pattern. Large-scale experiments using this SFME procedure showed a potential industrial application.

Field analyses of lavender volatile organic compounds: performance evaluation of a portable gas chromatography-mass spectrometry device.

INTRODUCTION: In situ analysis of volatile organic compounds (VOCs) emitted by plants is an important challenge in chemical ecology. The traditional approach usually consists in trapping compounds using dynamic headspace extraction (DHS) in-field, followed by gas chromatography analysis coupled with mass spectrometry (GC-MS and/or GC-FID) in the laboratory. OBJECTIVES: In this study, we evaluated the use of the new portable Torion T-9 GC-MS system for rapid and in situ analysis of VOCs emitted by fine lavender and lavandin species. MATERIAL AND METHODS: All field analyses were performed using a person-portable low-thermal mass GC system coupled with a miniature toroidal ion trap mass analyser (ppGC-ITMS): Torion T-9 portable GC-MS. Subsequently, multivariate statistical analyses were performed to determine chemical differences between species. RESULTS: Thirty compounds were separated and detected in all lavender above-ground samples in only 3 min of analysis. CONCLUSIONS: The portable GC-MS device enabled a rapid in-field distinction of Lavandula species based on their detected volatile profiles.

The Connectivity Fingerprint of the Fusiform Gyrus Captures the Risk of Developing Autism in Infants with Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by benign tumors throughout the body; it is generally diagnosed early in life and has a high prevalence of autism spectrum disorder (ASD), making it uniquely valuable in studying the early development of autism, before neuropsychiatric symptoms become apparent. One well-documented deficit in ASD is an impairment in face processing. In this work, we assessed whether anatomical connectivity patterns of the fusiform gyrus, a central structure in face processing, capture the risk of developing autism early in life. We longitudinally imaged TSC patients at 1, 2, and 3 years of age with diffusion compartment imaging. We evaluated whether the anatomical connectivity fingerprint of the fusiform gyrus was associated with the risk of developing autism measured by the Autism Observation Scale for Infants (AOSI). Our findings suggest that the fusiform gyrus connectivity captures the risk of developing autism as early as 1 year of age and provides evidence that abnormal fusiform gyrus connectivity increases with age. Moreover, the identified connections that best capture the risk of developing autism involved the fusiform gyrus and limbic and paralimbic regions that were consistent with the ASD phenotype, involving an increased number of left-lateralized structures with increasing age.

Early white matter development is abnormal in tuberous sclerosis complex patients who develop autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is prevalent in tuberous sclerosis complex (TSC), occurring in approximately 50% of patients, and is hypothesized to be caused by disruption of neural circuits early in life. Tubers, or benign hamartomas distributed stochastically throughout the brain, are the most conspicuous of TSC neuropathology, but have not been consistently associated with ASD. Widespread neuropathology of the white matter, including deficits in myelination, neuronal migration, and axon formation, exist and may underlie ASD in TSC. We sought to identify the neural circuits associated with ASD in TSC by identifying white matter microstructural deficits in a prospectively recruited, longitudinally studied cohort of TSC infants. METHODS: TSC infants were recruited within their first year of life and longitudinally imaged at time of recruitment, 12 months of age, and at 24 months of age. Autism was diagnosed at 24 months of age with the ADOS-2. There were 108 subjects (62 TSC-ASD, 55% male; 46 TSC+ASD, 52% male) with at least one MRI and a 24-month ADOS, for a total of 187 MRI scans analyzed (109 TSC-ASD; 78 TSC+ASD). Diffusion tensor imaging properties of multiple white matter fiber bundles were sampled using a region of interest approach. Linear mixed effects modeling was performed to test the hypothesis that infants who develop ASD exhibit poor white matter microstructural integrity over the first 2 years of life compared to those who do not develop ASD. RESULTS: Subjects with TSC and ASD exhibited reduced fractional anisotropy in 9 of 17 white matter regions, sampled from the arcuate fasciculus, cingulum, corpus callosum, anterior limbs of the internal capsule, and the sagittal stratum, over the first 2 years of life compared to TSC subjects without ASD. Mean diffusivity trajectories did not differ between groups. CONCLUSIONS: Underconnectivity across multiple white matter fiber bundles develops over the first 2 years of life in subjects with TSC and ASD. Future studies examining brain-behavior relationships are needed to determine how variation in the brain structure is associated with ASD symptoms.

Development of a Headspace Solid-Phase Microextraction Gas Chromatography-Mass Spectrometry Method to Study Volatile Organic Compounds (VOCs) Emitted by Lavender Roots.

A headspace solid-phase microextraction (HS-SPME) method combined with gas chromatography-mass spectrometry (GC/MS) was developed and optimized for the extraction and the analysis of volatile organic compounds (VOCs) from lavandin and fine lavender roots. Optimal parameters to extract volatile molecules from ground and intact roots were determined using a divinylbenzene-carboxen-polydimethylsiloxane (DVB/CAR/PDMS) coating fiber at 70 °C for 60 min. A total of 99 VOCs, including 40 monoterpenoids, 15 sesquiterpenoids, 1 diterpenoid and 2 coumarins were detected. The main compounds detected in lavandin roots were fenchol, borneol, and coumarin. Performances of the optimized SPME GC/MS method were evaluated via the comparison of VOC emissions between roots from different cultivars of fine lavender (7713 and maillette) and lavandin (abrial and grosso). Chemometric analysis, using partial least squares-discriminant analysis (PLS-DA), suggests fifteen significant features as potential discriminatory compounds. Among them, ß-phellandrene allows discrimination between lavender and lavandin varieties.

A Comparison of Point and Complete Electrode Models in a Finite Difference Model of Invasive Electrode Measurements.

Invasive electrophysiological measurement of brain activity is commonly employed during epilepsy surgery to provide final validation of required resection regions. These data are critical to clinical decision making, but manual expert analysis of these data can be complicated by the need to relate individual electrode measurements to specific brain regions. To improve analysis of these data with source analysis, accurate bioelectric models are needed. Given the proximity of the measurement locations to the generating cortical sources, modeling of electrodetissue interactions is particularly important for invasive measurements. Here, we evaluate the effect of a finite difference complete electrode model on the accuracy of leadfield computations for invasive electrocorticography. Our results show that in the vicinity of electrode locations, use of the simpler point electrode model produces large topographic and magnitude differences that will likely impact the accuracy of computed source localizations.

Cosmetic potentials of Prunus domestica L. leaves.

BACKGROUND: The current study presents new insight on the phytochemical content and biological activities of five Prunus domestica L. varieties ('Quetsche blanche de Létricourt', 'Mirabelle de Nancy', 'Perdrigon violet', 'Mirabelle de Provence', 'Reine-claude dorée'). RESULTS: The plum leaves were found to possess promising anti-aging activities by their capacity to inhibit 1,1-diphenyl-2-picrylhydrazyl (DPPH), elastase, hyaluronidase and lipoxygenase. After solid phase extraction (SPE), chlorogenic acid, rutin, quercetin and their derivatives were putatively identified by high-performance liquid chromatography coupled with tandem mass spectrometry using an electrospray ionization source (HPLC/ESI-MS/MS). CONCLUSION: The plum leaf, a by-product, provides an interesting valuable resource for use as a natural cosmetic product or as a food supplement. © 2017 Society of Chemical Industry.

Vetiver Essential Oil in Cosmetics: What Is New?

Background: Vetiver is a key ingredient for the perfume industry nowadays. However, with the constant and rapid changes of personal tastes, this appeal could vanish and this sector could decline quite quickly. New dissemination paths need to be found to tap this valuable resource. Methods: In this way, its potential use in cosmetics either as an active ingredient per se (with cosmeceutical significance or presenting antimicrobial activity) has hence been explored in vitro. Results: In this contribution, we demonstrated that vetiver essential oil displays no particularly significant and innovative cosmetic potential value in formulations apart from its scent already largely exploited. However, evaluated against twenty bacterial strains and two Candida species using the in vitro microbroth dilution method, vetiver oil demonstrated notably some outstanding activities against Gram-positive strains and against one Candida glabrata strain. Conclusions: Based on these findings, vetiver essential oil appears to be an appropriate aspirant for the development of an antimicrobial agent for medicinal purposes and for the development of a cosmetic ingredient used for its scent and displaying antimicrobial activity as an added value.

Estrogen-like and tissue-selective effects of 7-methoxycoumarin from Ficus umbellata (Moraceae): an in vitro and in vivo study.

BACKGROUND: Ficus umbellata is a medicinal plant previously shown to endow estrogenic properties. Its major component was isolated and characterized as 7-methoxycoumarin (MC). Noteworthy, coumarins and the respective active metabolite 7-hydroxycoumarin analogs have shown aromatase inhibitory activity, which is of particular interest in the treatment of estrogen-dependent cancers. The present work aimed at evaluating the estrogenic/antiestrogenic effects of MC in vitro and in vivo. METHODS: To do so, in vitro assays using E-screen and reporter gene were done. In vivo, a 3-day uterotrophic assay followed by a postmenopausal-like rat model to characterize MC as well as F. umbellata aqueous extract in ovariectomized Wistar rats was performed. The investigations focused on histological (vaginal and uterine epithelial height) and morphological (uterine wet weight, vagina stratification and cornification) endpoints, bone mass, biochemical parameters and lipid profile. RESULTS: MC induced a significant (p < 0.05) MCF-7 cell proliferation at a concentration of 0.1 µM, but did not inhibit the effect induced by estradiol in both E-screen and reporter gene assays. In vivo, MC treatment did not show an uterotrophic effect in both rat models used. However, MC (1 mg/kg) induced a significant increase (p < 0.01) of vaginal epithelial height. No significant change was observed with MC in abdominal fat weight, serum lipid levels and bone weight. CONCLUSION: These results suggest that MC has a weak estrogenic activity in vitro and in vivo that accounts only in part to the estrogenicity of the whole plant extract. MC could be beneficial with regard to vagina dryness as it showed a tissue specific effect without exposing the uterus to a potential tumorigenic growth.

Linear and Cyclic Depsipeptidomimetics with ß-Lactam Cores: A Class of New αv ß3 Integrin Receptor Inhibitors.

The αv ß3 integrin receptor plays an important role in tumor metastasis and tumor-induced angiogenesis. The inhibition of this receptor with diverse ligands, antibodies, or cyclic peptides is a promising research field for the treatment of a variety of tumors. The replacement of Phe-(Me)Val dipeptide by a ß-lactam ring in Cilengitide has led to new products that show higher inhibitory activity than the parent cyclopeptide. In particular, substitution of a peptide bond ß-lactam-NH-Asp linkage by a ß-lactam-O-Asp ester linkage increases the activity of the new cyclodepsipeptide. In the same way it has been found that open-chain compounds of the form Asp-ß-lactam-Arg can interact with the receptor and inhibit its activity moderately. The integrin inhibitory activity of the synthesized compounds has been established by using the CGH array, a method that appears to be a more reliable trial than the classical adhesion test.

Ethanol-extracted Cameroonian propolis exerts estrogenic effects and alleviates hot flushes in ovariectomized Wistar rats.

BACKGROUND: Since the biological properties of propolis depend to the plants that can be found in a specific region, propolis from unexplored regions attracts the attention of scientists. Ethanolic extract of Cameroonian propolis (EEP) is used to treat various ailments including gynecological problems and amenorrhea. Since there were no scientific data to support the above claims, the present study was therefore undertaken to assess estrogenic properties of Cameroonian propolis. METHODS: To achieve our goal, the ability of EEP to induce MCF-7 cells proliferation in E-screen assay as well as to activate estrogen receptors α (ERα) and ß (ERß) in cell-based reporter gene assays using human embryonic kidney cells (HEK293T) transfected with ERs was tested. Further, a 3-day uterotrophic assay was performed and the ability of EEP to alleviate hot flushes in ovariectomized adult rats was evaluated. RESULTS: In vitro, EEP showed an antiestrogenic activity in both HEK293T ER-α and ER-ß cells. In vivo, EEP induced a significant increase in a bell shape dose response manner of the uterine wet weight, the total protein levels in the uterus, the uterine and vaginal epithelium height and acini border cells of mammary gland with the presence of abundant eosinophil secretions. Moreover, EEP induced a significant decrease in the total number, average duration as well as frequency of hot flushes after 3 days of treatment in rat (equivalent to a month in woman). The dose of 150 mg/kg exhibited the most potent estrogenic effects among all the tested doses. The UPLC-HRMS analysis showed the presence of caffeic acid derivatives and trirtepernoids in EEP, which are well known endowed with estrogenic properties. CONCLUSION: These results suggest that Ethanolic extract of Cameroonian propolis has estrogen-like effects in vivo and may alleviate some menopausal problems such as vaginal dryness and hot flushes. Ethanol-extracted Cameroobian propolis exhibited in vitro and in vivo estrogen-like effects. This extract may contain promising phytoestrogens.

Estrogenic effects of Ficus umbellata Vahl. (Moraceae) extracts and their ability to alleviate some menopausal symptoms induced by ovariectomy in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ficus umbellata Vahl. (Moraceae) is a medicinal plant used in Cameroon to treat amenorrhea as well as other physiological disorders related to menopause. AIM OF STUDY: In order to justify scientifically its traditional use, the estrogen-like properties of the aqueous (AE) and methanol (MeOH) extracts of F. umbellata were investigated. MATERIAL AND METHODS: In vitro, the ability of different extracts of F. umbellata to activate estrogen receptors α (ERα) and ß (ERß) in cell-based reporter gene assays using human embryonic kidney (HEK293T) cells transfected with ERs was tested. In vivo, a 3-day uterotrophic assay and the capacity of the extracts to alleviate hot flushes in ovariectomized adult rats were tested. Using a bioassay-guided fractionation the major compound of F. umbellata was isolated and tested in vitro on HEK293T-ERα and ERß cells. RESULTS: AE and MeOH extracts significantly altered ERα as well as ERß activities. In vivo, both extracts significantly increase the uterine and vaginal epithelium thickness, and uterine total protein levels in a dose dependent manner. Interestingly, both extracts of F. umbellata at the dose of 100 mg/kg BW significantly decreased the total number, average duration as well as frequency of hot flushes in experimental rats compared to age-matched OVX controls. Finally, 7-methylumbelliferone, a coumarin was characterized as the major compound of F. umbellata; however this compound did not transactivate ERα as well ERß in vitro. CONCLUSION: These aforementioned results suggest that F. umbellata extracts as used by the traditional practitioner have estrogen-like effects and may alleviate some menopausal problems such as vaginal dryness and hot flushes.

Flavonoids, Breast Cancer Chemopreventive and/or Chemotherapeutic Agents.

Flavonoids are secondary metabolites abundantly present in commonly consumed fruits and vegetables. They possess diverse properties such as anti-inflammatory, anti-oxidant and anti-cancer. Epidemiologic studies suggest that an enrich flavonoids diet is linked to a decreased risk of breast cancer. These protective properties are due to the alteration of numerous signalling pathways involved in cancer-related phenomena such as inflammation and proliferation. Human clinical trials examining the effect of supplementation of some flavonoids on disease prevention have been conducted. There is no natural flavonoid that has been approved for the treatment of breast cancer. However, natural flavonoids served as lead compounds in the synthesis of cancer chemopreventive and/or therapeutic agents.

Tubers are neither static nor discrete: Evidence from serial diffusion tensor imaging.

OBJECTIVE: To assess the extent and evolution of tissue abnormality of tubers, perituber tissue, and normal-appearing white matter (NAWM) in patients with tuberous sclerosis complex using serial diffusion tensor imaging. METHODS: We applied automatic segmentation based on a combined global-local intensity mixture model of 3T structural and 35 direction diffusion tensor MRIs (diffusion tensor imaging) to define 3 regions: tuber tissue, an equal volume perituber rim, and the remaining NAWM. For each patient, scan, lobe, and tissue type, we analyzed the averages of mean diffusivity (MD) and fractional anisotropy (FA) in a generalized additive mixed model. RESULTS: Twenty-five patients (mean age 5.9 years; range 0.5-24.5 years) underwent 2 to 6 scans each, totaling 70 scans. Average time between scans was 1.2 years (range 0.4-2.9). Patient scans were compared with those of 73 healthy controls. FA values were lowest, and MD values were highest in tubers, next in perituber tissue, then in NAWM. Longitudinal analysis showed a positive (FA) and negative (MD) correlation with age in tubers, perituber tissue, and NAWM. All 3 tissue types followed a biexponential developmental trajectory, similar to the white matter of controls. An additional qualitative analysis showed a gradual transition of diffusion values across the tissue type boundaries. CONCLUSIONS: Similar to NAWM, tuber and perituber tissues in tuberous sclerosis complex undergo microstructural evolution with age. The extent of diffusion abnormality decreases with distance to the tuber, in line with known extension of histologic, immunohistochemical, and molecular abnormalities beyond tuber pathology.

Flavonoids, Breast Cancer Chemopreventive and/or Chemotherapeutic Agents

Flavonoids are secondary metabolites abundantly present in commonly consumed fruits and vegetables. They possess diverse properties such as anti-inflammatory, anti-oxidant and anti-cancer. Epidemiologic studies suggest that an enrich flavonoids diet is linked to a decreased risk of breast cancer. These protective properties are due to the alteration of numerous signalling pathways involved in cancer-related phenomena such as inflammation and proliferation. Human clinical trials examining the effect of supplementation of some flavonoids on disease prevention have been conducted. There is no natural flavonoid that has been approved for the treatment of breast cancer. However, natural flavonoids served as lead compounds in the synthesis of cancer chemopreventive and/or therapeutic agents.