Millettia dubia De Wild. (Fabaceae): Structural analysis of the oleanane-type glycosides and stimulation of the sweet taste receptors TAS1R2/TAS1R3.

From the root barks of a Central African tree Millettia dubia De Wild. (Fabaceae), ten previously undescribed oleanane-type glycosides were isolated by various chromatographic protocols. Their structures were elucidated by spectroscopic methods, mainly 2D NMR experiments and mass spectrometry, as mono- and bidesmosidic glycosides of mesembryanthemoidigenic acid, hederagenin and oleanolic acid. The stimulation of the sweet taste receptor TAS1R2/TAS1R3 by these glycosides was evaluated, and structure/activity relationships were proposed. Two of them showed an agonist effect on TAS1R2/TAS1R3.

The STOIC2021 COVID-19 AI challenge: Applying reusable training methodologies to private data.

Challenges drive the state-of-the-art of automated medical image analysis. The quantity of public training data that they provide can limit the performance of their solutions. Public access to the training methodology for these solutions remains absent. This study implements the Type Three (T3) challenge format, which allows for training solutions on private data and guarantees reusable training methodologies. With T3, challenge organizers train a codebase provided by the participants on sequestered training data. T3 was implemented in the STOIC2021 challenge, with the goal of predicting from a computed tomography (CT) scan whether subjects had a severe COVID-19 infection, defined as intubation or death within one month. STOIC2021 consisted of a Qualification phase, where participants developed challenge solutions using 2000 publicly available CT scans, and a Final phase, where participants submitted their training methodologies with which solutions were trained on CT scans of 9724 subjects. The organizers successfully trained six of the eight Final phase submissions. The submitted codebases for training and running inference were released publicly. The winning solution obtained an area under the receiver operating characteristic curve for discerning between severe and non-severe COVID-19 of 0.815. The Final phase solutions of all finalists improved upon their Qualification phase solutions.

Strengths, challenges, and strategies for implementing pragmatic multicenter randomized controlled trials (RCTs): example of the Personalized Citizen Assistance for Social Participation (APIC) trial.

BACKGROUND: Randomized controlled trials (RCTs) are rigorous scientific research designs for evaluating intervention effectiveness. However, implementing RCTs in a real-world context is challenging. To develop strategies to improve its application, it is essential to understand the strengths and challenges of this design. This study thus aimed to explore the strengths, challenges, and strategies for improving the implementation of a pragmatic multicenter, prospective, two-arm RCT evaluating the effects of the Personalized Citizen Assistance for Social Participation (Accompagnement-citoyen Personnalisé d'Intégration Communautaire: APIC; weekly 3-h personalized stimulation sessions given by a trained volunteer over a 12-month period) on older adults' health, social participation, and life satisfaction. METHODS: A multiple case study was conducted with 14 participants, comprising one research assistant, seven coordinators, and six managers of six community organizations serving older adults, who implemented the APIC in the context of a RCT. Between 2017 and 2023, qualitative data were extracted from 24 group meetings, seven semi-directed interviews, emails exchanged with the research team, and one follow-up document. RESULTS: Aged between 30 and 60 (median ± SIQR: 44.0 ± 6.3), most participants were women from organizations already offering social participation interventions for older adults and working with the public sector. Reported strengths of this RCT were its relevance in assessing an innovative intervention to support healthy aging, and the sharing of common goals, expertise, and strategies with community organizations. Challenges included difficulties recruiting older adults, resistance to potential control group assignments, design complexity, and efforts to mobilize and engage volunteers. The COVID-19 pandemic lockdown and health measures exacerbated challenges related to recruiting older adults and mobilizing volunteers and complicated delivery of the intervention. The strategies that mostly overcame difficulties in recruiting older adults were reducing sample size, simplifying recruitment procedures, emphasizing the health follow-up, extending partnerships, and recognizing and supporting volunteers better. Because of the lockdown and physical distancing measures, the intervention was also adapted for remote delivery, including via telephone or videoconferencing. CONCLUSION: Knowledge of the strengths and challenges of pragmatic RCTs can contribute to the development of strategies to facilitate implementation studies and better evaluate health and social participation interventions delivered under real-life conditions. TRIAL REGISTRATION: NCT03161860; Pre-results. Registered on May 22, 2017.

Integrated liver and serum proteomics uncover sexual dimorphism and alteration of several immune response proteins in an aging Werner syndrome mouse model.

Werner syndrome (WS) is a progeroid disorder caused by mutations in a protein containing both a DNA exonuclease and DNA helicase domains. Previous studies indicated that males lacking the helicase domain of the Wrn protein orthologue exhibited hepatic transcriptomic and metabolic alterations. In this study, we used a label-free liquid chromatography-tandem mass spectrometry approach to uncover proteins abundance associated with specific biological processes that differed depending on the age (four or ten months) and/or the genotype (wild type or Wrn mutant) in the serum and liver of mice. Principal component analysis of the proteomic data from both serum and hepatic tissue revealed a sexual dimorphism regardless of the age and the genotype of the mice. Moreover, although all Wrn mutant mice exhibited fatty liver by the age of ten months, a significant age and genotype dependent enrichment of proteins involved in lipid and fatty acid metabolic processes were uncovered only in males. Also, a genotype dependent increase in serum oxidant detoxification processes was observed in the serum of Wrn mutant males. Despite these sexual differences, several aspects of the immune system were affected in both females and males. Finally, an increase of specific immunoglobulin molecules was common in the liver and serum of both older Wrn mutant females and males. Such results suggest that specific immunoglobulin variants maybe associated with fatty liver progression in WS.

Clinical outcomes of screen-positive genome-wide cfDNA cases for trisomy 20: results from the global expanded NIPT Consortium.

Trisomy 20 has been shown to be one of the most frequent rare autosomal trisomies in patients that undergo genome-wide noninvasive prenatal testing. Here, we describe the clinical outcomes of cases that screened positive for trisomy 20 following prenatal genome-wide cell-free (cf.) DNA screening. These cases are part of a larger cohort of previously published cases. Members of the Global Expanded NIPT Consortium were invited to submit details on their cases with a single rare autosomal aneuploidy following genome-wide cfDNA screening for retrospective analysis. Clinical details including patient demographics, test indications, diagnostic testing, and obstetric pregnancy outcomes were collected. Genome-wide cfDNA screening was conducted following site-specific laboratory procedures. Cases which screened positive for trisomy 20 (n = 10) were reviewed. Clinical outcome information was available for 90% (9/10) of our screen-positive trisomy 20 cases; the case without diagnostic testing ended in a fetal demise. Of the nine cases with outcome information, one was found to have a mosaic partial duplication (duplication at 20p13), rather than a full trisomy 20. Only one case in the study cohort had placental testing; therefore, confined placental mosaicism could not be ruled out in most cases. Adverse pregnancy outcomes were seen in half of the cases, which could suggest the presence of underlying confined placental mosaicism or mosaic/full fetal trisomy 20. Based on our limited series, the likelihood of true fetal aneuploidy is low but pregnancies may be at increased risk for adverse obstetric outcomes and may benefit from additional surveillance.

Tensions experienced by case managers working in home care for older adults in Quebec: first level analysis of an institutional ethnography.

BACKGROUND: Case managers play a vital role in integrating the necessary services to optimise health-related goals and outcomes. Studies suggest that in home care, case managers encounter tensions in their day-to-day work, that is, disjuncture between what they should do, in theory, and what they actually do, in practice. However, direct exploration of these tensions is lacking. As such, this study aimed to describe the tensions encountered by case managers in public home care for older adults in Quebec and their influence on day-to-day work. METHODS: An institutional ethnography was conducted through observations of work, interviews and a survey with case managers working in home care in Quebec. Data were analysed using institutional ethnography first-level analysis procedures. This included mapping the work sequences as well as identifying the tensions experienced by case managers through the words they used. RESULTS: Three main tensions were identified. First, case managers perceive that, despite working to return hospitalised older adults at home safely, their work also aims to help free up hospital beds. Thus, they often find themselves needing to respond quickly to hospital-related inquiries or expedite requests for home care services. Second, they are supposed to delegate the care to "partners" (e.g., private organisations). However, they feel that they are in effect managing the quality of the services provided by the "partners." Consequently, they go to great lengths to ensure that good care will be provided. Finally, they must choose between meeting organisational requirements (e.g., reporting statistics about the work, documenting information in the older adults' file, doing mandatory assessments) and spending time providing direct care. This often leads to prioritising direct care provision over administrative tasks, resulting in minimal reporting of essential information. CONCLUSION: The results are discussed using the three lenses of professional practice context analyses (i.e., accountability, ethics, and professional-as-worker) to formulate recommendations for practice and research. They suggest that, despite their important role, case managers have limited power in home care (e.g., with partners, with the hospital).

Effect of Age-Friendly Communities Action Plan on Trajectories of Older Canadians' Depressive Symptoms Between 2018 and 2020: Multilevel Results From the Canadian Longitudinal Study on Aging.

As the COVID-19 pandemic impacted mental health, this longitudinal study examined the effect of age-friendly communities (AFC) action plan on older adults' depressive symptoms. Using the CLSA, the CLSA COVID-19 Questionnaire study, survey of Canadian municipalities, and the census, the depressive symptoms trajectories were modeled with multilevel multinomial regressions. Most respondents (66.1%) had non-depressed trajectories, 28.1% experienced a moderate increase in depressive symptoms, and 5.8% had a depressed trajectory. AFC action plans did not have a protective effect on these trajectories. Being a female, greater loneliness, lower income, ≥2 chronic conditions, inferior social participation, weaker sense of belonging, COVID-19 infection, and pandemic stressors predicted a depressed trajectory. Neighborhood's deprivation had a weak protective effect on the declining trajectory. Although AFC action plans provided no benefits during the pandemic, volunteers facilitating resource access and social interactions could limit any increase in depressive symptoms.

microRNAs are differentially expressed in equine plasma of horses with osteoarthritis and osteochondritis dissecans versus control horses.

Osteoarthritis (OA) is a leading cause of lameness in horses with no effective disease-modifying treatment and challenging early diagnosis. OA is considered a disease of the joint involving the articular cartilage, subchondral bone, synovial membrane, and ligaments. Osteochondritis dissecans (OCD) is a joint disease consisting of focal defects in the osteochondral unit which may progress to OA later in life. MicroRNAs (miRNAs) have been recognized as small non-coding RNAs that regulate a variety of biological processes and have been detected in biological fluids. MiRNAs are currently investigated for their utility as biomarkers and druggable targets for a variety of diseases. The current study hypothesizes that miRNA profiles can be used to actively monitor joint health and differences in miRNA profiles will be found in healthy vs diseased joints and that differences will be detectable in blood plasma of tested horses. Five horses with OA, OCD, and 4 controls (C) had blood plasma and synovial fluid collected. Total RNA, including miRNA was isolated before generating miRNA libraries from the plasma of the horses. Libraries were sequenced at the Schroeder Arthritis Institute (Toronto). Differential expression analysis was done using DESeq2 and validated using ddPCR. KEGG pathway analysis was done using mirPath v.3 (Diana Tools). 57 differentially expressed miRNAs were identified in OA vs C plasma, 45 differentially expressed miRNAs in OC vs C plasma, and 21 differentially expressed miRNAs in OA vs OCD plasma. Notably, miR-140-5p expression was observed to be elevated in OA synovial fluid suggesting that miR-140-5p may serve as a protective marker early on to attenuate OA progression. KEGG pathway analysis of differentially expressed plasma miRNAs showed relationships with glycan degradation, glycosaminoglycan degradation, and hippo signaling pathway. Interestingly, ddPCR was unable to validate the NGS data suggesting that isomiRs may play an integral role in miRNA expression when assessed using NGS technologies.

Retrospective study of perioperative antimicrobial use in horses undergoing elective laparoscopy at a single institution.

Antimicrobial stewardship has shown significant development in recent years. Perioperative prophylaxis accounts for a substantial volume of antimicrobial use and is a field in which improvements can likely be made. The objective of this study was to evaluate practices associated with perioperative antimicrobial use in equine elective laparoscopy at a single institution over a 21-year period and to determine whether antimicrobial therapy influenced the occurrence of postoperative complications. Medical records of horses that underwent elective laparoscopy at a teaching hospital from January 2000 to September 2021 were reviewed. Data obtained included signalment, surgeon, type and duration of procedure, perioperative antimicrobial use, and intraoperative and postoperative complications. Exact univariate logistic regression was used to explore the association between possible risk factors and occurrence of postoperative complications, as well as the association between year of presentation and time of antimicrobial administration. Duration of surgery was log-transformed to meet assumption of normality, followed by analysis of variance (ANOVA) to compare mean surgery time per procedure and postoperative complications. Significance was set at P < 0.05. Sixty horses met the inclusion criteria. All horses received antimicrobial prophylaxis, but none received intraoperative redosing. Only 13 horses (26%) received antimicrobials within 60 min of the first incision. Time of administration improved with each year of the study (P = 0.005). Only 17 horses (28%) received antimicrobials for less than 24 h, but median duration of antimicrobial therapy was 1.25 d (range: 0.25 to 10 d). Antimicrobial use practices at this institution differed from general recommendations for optimal perioperative prophylaxis, which suggests that intervention is required.

L'antibiogouvernance a connu un développement significatif ces dernières années. La prophylaxie peropératoire représente un volume important d'utilisation d'antimicrobiens et constitue un domaine dans lequel des améliorations peuvent probablement être apportées. L'objectif de cette étude était d'évaluer les pratiques associées à l'utilisation peropératoire d'antimicrobiens en laparoscopie élective équine dans un seul établissement sur une période de 21 ans et de déterminer si le traitement antimicrobien influençait la survenue de complications postopératoires. Les dossiers médicaux des chevaux ayant subi une laparoscopie élective dans un centre hospitalier universitaire de janvier 2000 à septembre 2021 ont été examinés. Les données obtenues comprenaient le signalement, le chirurgien, le type et la durée de la procédure, l'utilisation d'antimicrobiens peropératoires et les complications intra-opératoires et postopératoires. Une régression logistique univariée exacte a été utilisée pour explorer l'association entre les facteurs de risque possibles et la survenue de complications postopératoires, ainsi que l'association entre l'année de présentation et le moment de l'administration des antimicrobiens. La durée de la chirurgie a été transformée en log pour répondre à l'hypothèse de normalité, suivie d'une analyse de variance (ANOVA) pour comparer la durée moyenne de la chirurgie par procédure et les complications postopératoires. La signification a été fixée à P < 0,05. Soixante chevaux répondaient aux critères d'inclusion. Tous les chevaux ont reçu une prophylaxie antimicrobienne, mais aucun n'a reçu de dose supplémentaire durant la chirurgie. Seuls 13 chevaux (26 %) ont reçu des antimicrobiens dans les 60 minutes suivant la première incision. Le temps d'administration s'est amélioré avec chaque année d'étude (P = 0,005). Seulement 17 chevaux (28 %) ont reçu des antimicrobiens pendant moins de 24 heures, mais la durée médiane du traitement antimicrobien était de 1,25 jour (plage : 0,25 à 10 jours). Les pratiques d'utilisation des antimicrobiens dans cet établissement différaient des recommandations générales pour une prophylaxie peropératoire optimale, ce qui suggère qu'une intervention est nécessaire.(Traduit par Docteur Serge Messier).

Anoplasty and rectovaginal fistula repair in a gilt with atresia ani: A case report.

A 2-year-old female Vietnamese potbellied pig was referred to the Large Animal Teaching Hospital at the Ontario Veterinary College for anoplasty and rectovaginal fistula repair. The presence of atresia ani and rectovaginal fistula had been previously diagnosed. Contrast radiography was used to confirm the diagnosis and determine the position of the fistula and terminal rectum. Under general anesthesia, the urethra was catheterized. An incision was made at the anatomic location of the anus, the rectovaginal fistula was isolated through deep dissection, and a Penrose drain was placed around it for caudal retraction. Transvaginal catheter placement through the fistula and into the rectum assisted with anatomic location. Once the urogenital and gastrointestinal tracts were clearly identified, the fistula was transected as close to the vaginal cavity as possible. The vaginal defect was sutured, and the fistula tract was mobilized 90° and sutured to the skin, creating the anal canal. Postoperative complications included constipation and cystitis. The gilt passed feces 5 d after surgery and was discharged on Day 11 of hospitalization. Normal urination and defecation were observed at the time, and fecal incontinence was resolved. Six months after surgical intervention, the gilt remained continent and no complications were reported. Key clinical message: Anoplasty and rectovaginal fistula repair were completed successfully in a gilt. Preservation of the fistula and its use during anal reconstruction may provide an internal anal sphincter and may be associated with improved continence.

Anoplastie et réparation de la fistule recto-vaginale chez une cochette avec atrésie anale : rapport de cas. Une femelle cochon vietnamien de 2 ans a été référée au Large Animal Teaching Hospital du Ontario Veterinary College pour une anoplastie et réparation d'une fistule recto-vaginale. La présence d'une atrésie anale et d'une fistule recto-vaginale avait déjà été diagnostiquée. Une radiographie de contraste a été utilisée pour confirmer le diagnostic et déterminer la position de la fistule et du rectum terminal. Sous anesthésie générale, l'urètre a été cathétérisé. Une incision a été faite à l'emplacement anatomique de l'anus, la fistule recto-vaginale a été isolée par dissection profonde et un drain de Penrose a été placé autour d'elle pour la rétraction caudale. Le placement d'un cathéter transvaginal à travers la fistule et dans le rectum a aidé avec la localisation anatomique. Une fois les voies urogénitale et gastro-intestinale clairement identifiées, la fistule a été sectionnée aussi près que possible de la cavité vaginale. Le défaut vaginal a été suturé et le trajet de la fistule a été mobilisé à 90° et suturé à la peau, créant le canal anal. Les complications postopératoires incluaient la constipation et la cystite. La cochette a expulsé des matières fécales 5 jours après la chirurgie et a obtenu son congé le 11e jour d'hospitalisation. Une miction et une défécation normales ont été observées à ce moment-là, et l'incontinence fécale a été résolue. Six mois après l'intervention chirurgicale, la cochette présentait encore de la continence urinaire et aucune complication n'a été signalée.Message clinique clé :L'anoplastie et la réparation de la fistule recto-vaginale ont été réalisées avec succès chez une cochette. La préservation de la fistule et son utilisation lors de la reconstruction anale peuvent fournir un sphincter anal interne et peuvent être associées à une meilleure continence.(Traduit par Dr Serge Messier).

Pulse-SILAC and Interactomics Reveal Distinct DDB1-CUL4-Associated Factors, Cellular Functions, and Protein Substrates.

Cullin-RING finger ligases represent the largest family of ubiquitin ligases. They are responsible for the ubiquitination of ∼20% of cellular proteins degraded through the proteasome, by catalyzing the transfer of E2-loaded ubiquitin to a substrate. Seven cullins are described in vertebrates. Among them, cullin 4 (CUL4) associates with DNA damage-binding protein 1 (DDB1) to form the CUL4-DDB1 ubiquitin ligase complex, which is involved in protein ubiquitination and in the regulation of many cellular processes. Substrate recognition adaptors named DDB1/CUL4-associated factors (DCAFs) mediate the specificity of CUL4-DDB1 and have a short structural motif of approximately forty amino acids terminating in tryptophan (W)-aspartic acid (D) dipeptide, called the WD40 domain. Using different approaches (bioinformatics/structural analyses), independent studies suggested that at least sixty WD40-containing proteins could act as adaptors for the DDB1/CUL4 complex. To better define this association and classification, the interaction of each DCAFs with DDB1 was determined, and new partners and potential substrates were identified. Using BioID and affinity purification-mass spectrometry approaches, we demonstrated that seven WD40 proteins can be considered DCAFs with a high confidence level. Identifying protein interactions does not always lead to identifying protein substrates for E3-ubiquitin ligases, so we measured changes in protein stability or degradation by pulse-stable isotope labeling with amino acids in cell culture to identify changes in protein degradation, following the expression of each DCAF. In conclusion, these results provide new insights into the roles of DCAFs in regulating the activity of the DDB1-CUL4 complex, in protein targeting, and characterized the cellular processes involved.

Impact of a Whey Protein Hydrolysate Treated by Electrodialysis with Ultrafiltration Membrane on the Development of Metabolic Syndrome and the Modulation of Gut Microbiota in Mice.

The development of Metabolic Syndrome (MetS) affects a large number of people around the world and represents a major issue in the field of health. Thus, it is important to implement new strategies to reduce its prevalence, and various approaches are currently under development. Recently, an eco-friendly technology named electrodialysis with ultrafiltration membrane (EDUF) was used successfully for the first time at a semi-industrial scale to produce three fractions concentrated in bioactive peptides (BPs) from an enzymatically hydrolyzed whey protein concentrate (WPC): the initial (F1), the final (F2) and the recovery fraction (F3), and it was demonstrated in vitro that F3 exhibited interesting DPP-IV inhibitory effects. Therefore, the present study aimed to evaluate the effect of each fraction on in vivo models of obesity. A daily dose of 312.5 mg/kg was administered to High Fat/High Sucrose diet (HFHS) induced C57BL6/J mice for eight weeks. The physiological parameters of each group and alterations of their gut microbiota by the fractions were assessed. Little effect of the different fractions was demonstrated on the physiological state of the mice, probably due to the digestion process of the BP content. However, there were changes in the gut microbiota composition and functions of mice treated with F3.

Key Age-Friendly Components of Municipalities that Foster Social Participation of Aging Canadians: Results from the Canadian Longitudinal Study on Aging.

Municipalities can foster the social participation of aging adults. Although making municipalities age-friendly is recognized as a promising way to help aging adults stay involved in their communities, little is known about the key components (e.g., services and structures) that foster social participation. This study thus aimed to identify key age-friendly components (AFC) best associated with the social participation of older Canadians. Secondary analyses were carried out using baseline data from the Canadian Longitudinal Study on Aging (n = 25,411) in selected municipalities (m = 110 with ≥ 30 respondents), the Age-friendly Survey, and census data. Social participation was estimated based on the number of community activities outside the home per month. AFC included housing, transportation, outdoor spaces and buildings, safety, recreation, workforce participation, information, respect, health, and community services. Multilevel models were used to examine the association between individual social participation, key AFC, and environmental characteristics, while controlling for individual characteristics. Aged between 45 and 89, half of the participants were women who were engaged in 20.2±12.5 activities per month. About 2.5% of the variance in social participation was attributable to municipalities. Better outdoor spaces and buildings (p < 0.001), worse communication and information (p < 0.01), and lower material deprivation (p < 0.001) were associated with higher social participation. Age was the only individual-level variable to have a significant random effect, indicating that municipal contexts may mediate its impact with social participation. This study provides insights to help facilitate social participation and promote age-friendliness, by maintaining safe indoor and outdoor mobility, and informing older adults of available activities.

Hypermutator emergence in experimental Escherichia coli populations is stress-type dependent.

Genotypes exhibiting an increased mutation rate, called hypermutators, can propagate in microbial populations because they can have an advantage due to the higher supply of beneficial mutations needed for adaptation. Although this is a frequently observed phenomenon in natural and laboratory populations, little is known about the influence of parameters such as the degree of maladaptation, stress intensity, and the genetic architecture for adaptation on the emergence of hypermutators. To address this knowledge gap, we measured the emergence of hypermutators over ~1,000 generations in experimental Escherichia coli populations exposed to different levels of osmotic or antibiotic stress. Our stress types were chosen based on the assumption that the genetic architecture for adaptation differs between them. Indeed, we show that the size of the genetic basis for adaptation is larger for osmotic stress compared to antibiotic stress. During our experiment, we observed an increased emergence of hypermutators in populations exposed to osmotic stress but not in those exposed to antibiotic stress, indicating that hypermutator emergence rates are stress type dependent. These results support our hypothesis that hypermutator emergence is linked to the size of the genetic basis for adaptation. In addition, we identified other parameters that covaried with stress type (stress level and IS transposition rates) that might have contributed to an increased hypermutator provision and selection. Our results provide a first comparison of hypermutator emergence rates under varying stress conditions and point towards complex interactions of multiple stress-related factors on the evolution of mutation rates.

Phytochemical, Geographical, and Pharmacological Retrospect of Genus Torilis.

BACKGROUND: Genus Torilis (Apiaceae) known as hedge parsley, encompasses 11-13 species distributed worldwide and shows potential pharmacological uses. Its phytochemical pattern is highly diversified including many phenolic and terpenic compounds. OBJECTIVE: This research-review provides new highlighting of structural organizations, structure-activity trends, taxonomical, tissue and geographical distribution of phytocompounds of Torilis genus from extensive statistical analyses of available data. METHODS: In extenso, exploration of documented literature and statistical data analyses were applied to update the phytochemical pool of the genus under several aspects including structural diversity, geographical distribution, biological compartmentations and pharmacological activities. RESULTS: Phytoconstituents were classified into homogeneous clusters that revealed to be associated with chemical constitutions (aglycone types, chemical groups) and distributions (through species, tissues, geographical). About bioactivities, terpenes were studied from a pharmacological point of view with relatively high frequencies for antifungal, antibacterial, cytotoxic and anti-inflammatory activities. Preliminary structure-activity relationships were highlighted implying opposite effects between hydroxylation and methylation in favor of different activities. Crude extracts and isolated compounds have shown several biological activities (antibacterial, anticancer, antiangiogenic, antiproliferative, etc.), thus providing authentic scientific proof for their diverse uses in folk medicines. CONCLUSION: The phytochemistry of the genus Torilis promises important perspectives in matters of pharmacological activities. These perspectives call for further investments in pharmacology because of (i) unbalance between phenolic and terpenic compounds according to the countries and (ii) more advanced current states of structural elucidations compared to biological evaluations.

Increased Binding of von Willebrand Factor to Sub-Endothelial Collagen May Facilitate Thrombotic Events Complicating Bothrops lanceolatus Envenomation in Humans.

Consumption coagulopathy and hemorrhagic syndrome exacerbated by blood anticoagulability remain the most important causes of lethality associated with Bothrops snake envenomation. Bothrops venom also engages platelet aggregation on the injured endothelium via von Willebrand factor (vWF) interactions. Besides platelet aggregation, some Bothrops venom toxins may induce qualitative thrombopathy, which has been in part related to the inhibition of vWF activation. We tested whether B. lanceolatus venom impaired vWF to collagen(s) binding (vWF:CB) activity. Experiments were performed with B. lanceolatus crude venom, in the presence or absence of Bothrofav, a monospecific B. lanceolatus antivenom. Venom of B. lanceolatus fully inhibited vWF to collagen type I and III binding, suggesting venom interactions with the vWF A3 domain. In contrast, B. lanceolatus venom increased vWF to collagen type VI binding, suggesting the enhancement of vWF binding to collagen at the vWF A1 domain. Hence, B. lanceolatus venom exhibited contrasting in vitro effects in terms of the adhesive properties of vWF to collagen. On the other hand, the antivenom Bothrofav reversed the inhibitory effects of B. lanceolatus venom on vWF collagen binding activity. In light of the respective distribution of collagen type III and collagen type VI in perivascular connective tissue and the sub-endothelium, a putative association between an increase in vWF:CB activity for collagen type VI and the onset of thrombotic events in human B. lanceolatus envenomation might be considered.

Patient attitudes and preferences about expanded noninvasive prenatal testing.

Introduction: Noninvasive prenatal testing (NIPT) using cell-free DNA (cfDNA) is typically carried out to screen for common fetal chromosomal anomalies, with the option to screen for a wider range of chromosomal changes (expanded NIPT) becoming increasingly available. However, little is known about pregnant patients' attitudes and preferences regarding expanded NIPT. Methods: To address this gap, we surveyed general-risk patients having first-tier cfDNA screening at a private prenatal clinic on their expectations for expanded NIPT. Patients were asked questions regarding their current pregnancy and previous pregnancy history, their opinions on fetal DNA screenings during pregnancy and incidental findings, information and opinions on financial resources for NIPT, as well as socio-cultural questions to determine patient demographics. Results: Of the 200 survey participants, the majority were educated, self-reported as white, had a higher than average income, and reported no aneuploidy risk factors. When asked what information they would like to receive from cfDNA screening, the vast majority of participants wanted all information available that could have an immediate impact on fetal health (88%) or an immediate impact on infant health from birth (82%). Many participants also wanted information that could have a future impact on the child's health or an immediate or future impact on the pregnant woman's own health. Most participants wanted information about the sex of fetus (86%) and common trisomies (71%), with almost half of participants desiring information about rare autosomal aneuploidies and/or all genetic information that may affect the baby. In addition, participants were found to be comfortable screening for conditions that are well-known, influence care during pregnancy, and are treatable. Finally, while most respondents either had insurance coverage for NIPT or were able to afford NIPT out of pocket, the majority of our participants felt that expanded NIPT should be either free for everyone or for those considered high risk. Discussion: Our findings suggest that with appropriate pre-test counseling, pregnant patients may choose NIPT for an expanding list of conditions.

Floral scent of the Mediterranean fig tree: significant inter-varietal difference but strong conservation of the signal responsible for pollinator attraction.

For thousands of years, humans have domesticated different plants by selecting for particular characters, often affecting less-known traits, including the volatile organic compounds (VOCs) emitted by these plants for defense or reproduction. The fig tree Ficus carica has a very wide range of varieties in the Mediterranean region and is selected for its traits affecting fruits, including pollination, but the effect of human-driven diversification on the VOCs emitted by the receptive figs to attract their pollinator (Blastophaga psenes) is not known. In the present study, VOCs from receptive figs of eight varieties in northern Morocco, were collected at different times within the manual pollination period and analyzed by gas chromatography-mass spectrometry. Genetic analyses using microsatellite loci were performed on the same varieties. Despite strong inter-varietal differences in the quantity and relative proportions of all VOCs, the relative proportions of the four pollinator-attractive VOCs showed limited variation among varieties. There was no significant correlation between genetic markers and chemical profiles of the different varieties. While diversification driven by humans has led to differences between varieties in VOC profiles, this paper suggests that throughout the process of domestication and varietal diversification, stabilizing selection has maintained a strong signal favoring pollinator attraction.

Trajectories of health-related quality of life and their predictors in adult COVID-19 survivors: A longitudinal analysis of the Biobanque Québécoise de la COVID-19 (BQC-19).

PURPOSE: A significant number of people will experience prolonged symptoms after COVID-19 infection that will greatly impact functional capacity and quality of life. The aim of this study was to identify trajectories of health-related quality of life (HRQOL) and their predictors among adults diagnosed with COVID-19. METHODS: This is a retrospective analysis of an ongoing prospective cohort study (BQC-19) including adults (≥18y) recruited from April 2020 to March 2022. Our primary outcome is HRQOL using the EQ-5D-5L scale. Sociodemographic, acute disease severity, vaccination status, fatigue, and functional status at onset of the disease were considered as potential predictors. The latent class mixed model was used to identify the trajectories over an 18-month period in the cohort as a whole, as well as in the inpatient and outpatient subgroups. Multivariable and univariable regressions models were undertaken to detect predictors of decline. RESULTS: 2163 participants were included. Thirteen percent of the outpatient subgroup (2 classes) and 28% in the inpatient subgroup (3 classes) experienced a more significant decline in HRQOL over time than the rest of the participants. Among all patients, age, sex, disease severity and fatigue, measured on the first assessment visit or on the first day after hospital admission (multivariable models), were identified as the most important predictors of HRQOL decline. Each unit increase in the SARC-F and CFS scores increase the likelihood of belonging to the declining trajectory (univariable models). CONCLUSION: Although to different degrees, similar factors explain the decline in HRQOL over time among the overall population, people who have been hospitalized or not. Clinical functional capacity scales could help to determine the risk of HRQOL decline.

Sex-Related Effects of Adrenergic Drugs on Conditioned Pain Modulation: A Randomized Controlled Cross-Over Double-Blind Trial.

Objective: Endogenous pain inhibition can be investigated using conditioned pain modulation (CPM). CPM efficacy has been reported to be influenced by various factors, such as gender and cardiovascular (autonomic) activity. The aim of this study is to describe the effect of pharmacological manipulations of autonomic activity on CPM efficacy. Methods: Thirty healthy participants were enrolled to assess CPM efficacy in 4 experimental sessions. The first session consisted of the determination of baseline CPM effectiveness. The three following sessions were performed in a randomized order and consisted of the injection of (1) esmolol, (2) ephedrine, or (3) placebo, before the conditioning stimulus. Pain intensity induced by using a contact heat stimulation thermode was compared before and after a cold-pressure conditioning stimulus to evaluate CPM effectiveness. Results: Our results show that inhibiting sympathetic nervous activity with esmolol did not have a significant effect on CPM. Conversely, enhancing sympathetic nervous activity with ephedrine increased CPM effectiveness in healthy women but decreased it in men. Conclusions: Increasing sympathetic activity with adrenergic agonists, such as ephedrine, could improve CPM effectiveness in women. It will be interesting to verify if the same results are present in patients suffering from chronic pain and if adrenergic agonists could have better therapeutic effects in women showing reduced CPM effectiveness.