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AimThe anticholinergic properties of medications are associated with poorer cognitive performance in schizophrenia. Numerous scales have been developed to assess anticholinergic burden and yet, there is no consensus indicating which anticholinergic burden scale is more relevant for patients with schizophrenia. We aimed to identify valid scales for estimating the risk of iatrogenic cognitive impairment in schizophrenia.MethodsWe identified 27 scales in a literature review. The responses to neuropsychological tests of 839 individuals with schizophrenia or schizoaffective disorder in the FACE-SZ database were collected between 2010 and 2021. We estimated the association between objective global cognitive performance and the 27 scales, the number of psychotropic drugs, and chlorpromazine and lorazepam equivalents in bivariable regressions in a cross-sectional design. We then adjusted the bivariable models with covariates: the predictors significantly associated with cognitive performance in multiple linear regressions were considered to have good concurrent validity to assess cognitive performance.ResultsEight scales, the number of psychotropic drugs, and drug equivalents were significantly associated with cognitive impairment. The number of psychotropic drugs, the most convenient predictor to compute, was associated with worse executive function (Standardized β = −0.12, p = .004) and reasoning (Standardized β = −0.08, p = .037).ConclusionAnticholinergic burden, the number of psychotropic drugs, and drug equivalents were weakly associated with cognition, thus suggesting that cognitive impairment in schizophrenia and schizoaffective disorder is explained by factors other than medication. The number of psychotropic drugs was the most parsimonious method to assess the risk of iatrogenic cognitive impairment.

BackgroundAbout 10–20% of pancreas allografts are still lost in the early postoperative period despite the identification of numerous detrimental risk factors that correlate with graft thrombosis.MethodsWe conducted a multicenter study including 899 pancreas transplant recipients between 2000 and 2018. Early pancreas failure due to complete thrombosis, long-term pancreas, kidney and patient survivals were analyzed and adjusted to donor, recipient and perioperative variables using a multivariate cause-specific Cox model stratified to transplant centers.ResultsPancreas from donors with history of hypertension (6.7%), as well as with high body mass index (BMI), were independently associated with an increased risk of pancreas failure within the first 30 post-operative days (respectively, HR= 2.57, 95% CI from 1.35 to 4.89 and HR= 1.11, 95% CI from 1.04 to 1.19). Interaction term between hypertension and BMI was negative. Donor hypertension also impacted long-term pancreas survival (HR= 1.88, 95% CI from 1.13 to 3.12). However, when pancreas survival was calculated after the postoperative day 30, donor hypertension was no longer a significant risk factor (HR= 1.22, 95% CI from 0.47 to 3.15). A lower pancreas survival was observed in patients receiving a pancreas from a hypertensive donor without RAAS (Renin Angiotensin Aldosterone System) blockers compared to others (50% vs 14%, p < 0.001). Pancreas survival was similar among non-hypertensive donors and hypertensive ones under RAAS blockers.ConclusionDonor hypertension was a significant and independent risk factor of pancreas failure. The well-known pathogenic role of renin-angiotensin-aldosterone system seems to be involved in the genesis of this immediate graft failure.

Objectives: This study aims to map sexual and reproductive health and rights (SRHR) policies, strategies, and interventions targeting young migrants and describe the patterns of organisation, resources, and services across Sweden’s 21 regions.Methods: We conducted a document analysis of accessible online documents on SRHR policies, strategies, and interventions targeting young migrants in Sweden’s 21 regions. We used ideal-type analysis of the documents to create a typology, which formed the basis of a ratings system illustrating variations in organisation, resources, and services across regions.Results: Findings suggest that efforts aimed at addressing young migrants’ SRHR are fragmented and unequal across regions. While SRHR policies and strategies are commonplace, they routinely lack specificity. Available resources vary depending on region and resource type. Additionally, information and interventions, although common, do not consistently meet the specific needs of migrant youths.Conclusion: This study suggests that fragmented efforts are fuelling geographic inequalities in fulfilling SRHR among young migrants. There is an urgent need to improve national coordination and collaboration between national and local actors in SRHR efforts targeting young migrants to ensure equity.

Objectives(i) To classify training sessions of elite female cyclists according to an intensity index based on a longitudinal follow-up using multiparametric data collected in situ (ii) to measure the effect of estimated menstrual cycle (MC) phases and oral contraceptive pills (OC) phases on the athletes' training responses on each type of training identified.MethodThirteen elite French cyclists were followed up over 30 months and 5,190 training sessions were collected and 81 MC/OCs full cycles analyzed. Power sensors and position devices captured training data in situ, which was summarized into 14 external load variables. Principal Component Analysis and K-means clustering were used to identify cycling sessions according to an intensity load index. The clusters were then verified and categorized through the analysis of heart rate and rate of perceived effort. A calendar method was used to estimate 3 phases of the MC: menstruation, mid-cycle phase (MP) and late-cycle phase (LP). Two phases were defined among monophasic OC users: pills' taking/withdrawal.ResultsFour main types of training effort were identified: Intensive, Long, Medium and Light. In the MC group (n = 7; 52 cycles), the intensity index is 8% higher during the mid-cycle (vs. menstrual phase, p = 0.032) in the Intensive effort sessions. No differences were observed in Long, Medium or Light effort, nor between the phases of pills' taking/withdrawal among OC users.ConclusionThe clustering analyses developed allows a training classification and a robust method to investigate the influence of the MC/OC in situ. A better training response during the mid-cycle when the sessions are the most intense suggest an impact of the MC when the athletes approach their maximal capacity.

In the wake of the 2008 global financial crisis, Iceland launched a bid to join the European Union. Joining the EU was presented domestically as a key to economic recovery and as a preventative measure against future economic distress. The bid itself was framed within a rapidly shifting political landscape, set against a backdrop of spreading economic malaise across Europe, accompanied by economic bailout plans and austerity measures. Several aspects of the bid's ultimate failure demonstrate the importance of identities and narratives around national independence and European integration. Most saliently, widespread perceptions about what it would mean to join the EU, particularly around sensitive notions of sovereignty, proved insurmountable to the more economistic rationale of the pro-EU campaign. The Icelandic bid thus presents a distinct opportunity to drill down into the complex relationships between austerity economics, popular politics, and the European integration project, with significant policy implications. To better understand the emergence of the bid and its failure in sociopolitical terms we assess different conceptual frameworks, including functionalist, intergovernmentalist, and post-functionalist approaches and theoretical perspectives on crisis and contentious politics. We also include voices of Icelandic citizens from civil society and government collected in research interviews between 2012 and 2018. Overall, our comparative theoretical approach and original case data sharpen an emphasis in the social sciences and policy research on the importance of cultural narrative and identity as key determinants of EU integration.

Background: Moebius Syndrome (MBS) is a rare congenital neurological disorder characterized by paralysis of facial nerves, impairment of ocular abduction and other variable abnormalities. MBS has been attributed to both environmental and genetic factors as potential causes. Until now only two genes, PLXND1 and REV3L have been identified to cause MBS.Results: We present a 9-year-old male clinically diagnosed with MBS, presenting facial palsy, altered ocular mobility, microglossia, dental anomalies and congenital torticollis. Radiologically, he lacks both abducens nerves and shows altered symmetry of both facial and vestibulocochlear nerves. Whole-exome sequence identified a de novo missense variant c.643G>A; p.Gly215Arg in CHN1, encoding the α2-chimaerin protein. The p.Gly215Arg variant is located in the C1 domain of CHN1 where other pathogenic gain of function variants have been reported. Bioinformatic analysis and molecular structural modelling predict a deleterious effect of the missense variant on the protein function.Conclusion: Our findings support that pathogenic variants in the CHN1 gene may be responsible for different cranial congenital dysinnervation syndromes, including Moebius and Duane retraction syndromes. We propose to include CHN1 in the genetic diagnoses of MBS.

IntroductionPersistent pulmonary hypertension of the newborn (PPHN) is a life-threatening condition characterized by hypoxemia due to elevated pulmonary vascular resistance. PPHN commonly arises secondary to various underlying conditions, including infection, meconium aspiration, and respiratory distress syndrome. Management includes pulmonary vasodilators, mechanical ventilation, oxygen supplementation, vasopressors, and volume replacement. Stüve–Wiedemann syndrome (SWS), a rare genetic disorder characterized by bone dysplasia, respiratory distress, hyperthermia, and swallowing difficulties, may present with pulmonary hypertension, indicating a poor prognosis.Case descriptionA term female neonate presented with secondary respiratory failure and severe PPHN of unknown etiology on the second day of life, necessitating intubation. Clinical findings included facial dysmorphia, camptodactyly, skeletal anomalies, and generalized muscular hypotonia. High-frequency oscillation ventilation and surfactant administration yielded marginal improvement. On the third day of life, a severe pulmonary hypertensive crisis necessitated inhaled and systemic pulmonary vasodilators along with volume and catecholamine therapy. Whole exome sequencing revealed a homozygous mutation in the leukemia inhibitory factor receptor (LIFR) gene, consistent with Stüve–Wiedemann syndrome.Discussion/conclusionThe case underscores the importance of considering and prompting evaluation of rare genetic causes in the differential diagnosis of PPHN, especially when other abnormalities are present and conventional therapies prove inadequate. Therapeutic strategies must account for the different pathophysiology of primary PPHN including vascular remodeling, as seen in SWS, which may not respond to pulmonary vasodilators typically employed in secondary PPHN due to vasoconstriction. In this case, the patient responded well to treatment for primary PPHN, but the use of high-frequency oscillation ventilation and surfactant was not helpful.

IntroductionA study was conducted to investigate if an individual’s trust in law enforcement affects their perception of the emotional facial expressions displayed by police officers.MethodsThe study invited 77 participants to rate the valence of 360 face images. Images featured individuals without headgear (condition 1), or with a baseball cap (condition 2) or police hat (condition 3) digitally added to the original photograph. The images were balanced across sex, race/ethnicity (Asian, African American, Latine, and Caucasian), and facial expression (Happy, Neutral, and Angry). After rating the facial expressions, respondents completed a survey about their attitudes toward the police.ResultsThe results showed that, on average, valence ratings for “Angry” faces were similar across all experimental conditions. However, a closer examination revealed that faces with police hats were perceived as angrier compared to the control conditions (those with no hat and those with a baseball cap) by individuals who held negative views of the police. Conversely, participants with positive attitudes toward the police perceived faces with police hats as less angry compared to the control condition. This correlation was highly significant for angry faces (p < 0.01), and stronger in response to male faces compared to female faces but was not significant for neutral or happy faces.DiscussionThe study emphasizes the substantial role of attitudes in shaping social perception, particularly within the context of law enforcement.

For over two decades, Florida citrus growers have been heavily using copper sprays to combat citrus canker (Xanthomonas citri subsp. citri; Xcc), but it raises the risk of developing resistant bacterial strains and excessive accumulation in the soil. Alternative methods are needed to reduce copper dependency and better manage Xcc. Therefore, we screened copper-alternative products against canker on young seedlings in the greenhouse and mature trees in a commercial grove in Florida, USA. In the greenhouse, we evaluated the efficacy of single foliar application of new plant defense inducers (PDI), ‘PDI5’, ‘PDI26’, and ‘PDI31’, and a commercially available systemic acquired resistance inducer, Actigard (drench; 2g/tree), applied two days before injection-infiltration with citrus canker bacterium Xcc (104 CFU/ml), on two-year-old Valencia trees. All three PDIs, sprayed at 500 ppm, as well as Actigard (drench), effectively reduced canker severity on the inoculated leaves in the greenhouse (P ≤0.02). In the grove, we tested new antimicrobials, Mastercop ‘MC’ (21.46% copper sulfate pentahydrate; metallic copper equivalent 5.4%) at concentrations of 1.12 kg/ha, 1.68 kg/ha and 2.24 kg/ha, ‘AM’ at 1.68 kg/ha and 2.24 kg/ha, and a nutrient solution (AGRO-MOS) at 1.12 kg/ha for canker suppression on 4–6-year-old Hamlin trees. Kocide 2000 (growers’ standard control; metallic copper equivalent 30%; 3.92 kg/ha) was used as a control check. Although 2021 was not as conducive for citrus canker due to the relatively dry spring months in the field, our results showed that the six sprays of AM (2.24 kg/ha) or MC (1.68 kg/ha, and 2.24 kg/ha), in 2022, provided excellent control of Xcc, with a significant reduction in disease incidence in leaves and fruits, and disease severity in fruits, similar to Kocide 2000. The results indicate that antimicrobials, AM and MC, and plant defense inducers PDI5, PDI26, and PDI31 can be part of an integrated pest management (IPM) program with copper for managing citrus canker. Reducing the frequency and amount of copper applications can help reduce pesticide and application expenses, lower risks of copper buildup in the soil and toxicity for citrus trees and reduce the risk of the emergence of copper-resistant Xcc strains. Further research on these products is needed to assess their long-term effectiveness and potential environmental risks.

This research explores early Event-Related Potentials (ERPs) sensitivity to facial stimuli, investigating various facial features aimed to unveil underlying neural mechanisms. Two experiments, each involving 15 undergraduate students, utilized a multidimensional stimulus set incorporating race, gender, age, emotional expression, face masks, and stimulus orientation. Findings highlight significant modulations in N170 and P200 amplitudes and latencies for specific attributes, replicating prior research and revealing novel insights. Notably, age-related facial feature variations, facial inversion, and the presence of face masks significantly impact neural responses. Several speculative explanations are proposed to elucidate these results: First, the findings lend support to the idea that the increased N170 amplitude observed with facial inversion is closely tied to the activation of object-sensitive neurons. This is further bolstered by a similar amplitude increase noted when masks (effective objects) are added to faces. Second, the absence of an additional amplitude increase, when inverting face images with face masks suggests that neural populations may have reached a saturation point, limiting further enhancement. Third, the study reveals that the latency deficit in N170 induced by facial inversion is even more pronounced in the subsequent ERP component, the P200, indicating that face inversion may impact multiple stages of face processing. Lastly, the significant increase in P200 amplitude, typically associated with face typicality, for masked faces in this study aligns with previous research that demonstrated elevated P200 amplitudes for scrambled faces. This suggests that obscured faces may be processed as typical, potentially representing a default state in face processing.

IntroductionRoyal Canadian Mounted Police (RCMP) officers self-report high levels of mental health disorder symptoms, such as alcohol use disorder, generalized anxiety disorder, major depressive disorder, panic disorder, and posttraumatic stress disorder. Participation in regular mental health monitoring has been associated with improved mental health disorder symptom reporting and may provide an accessible tool to support RCMP mental health. The current study assessed relationships between self-reported mental health disorder symptoms and the completion of daily surveys (i.e., daily mental health disorder symptom monitoring) by RCMP cadets during the Cadet Training Program (CTP).MethodsParticipants were RCMP cadets (n = 394; 76.1% men) in the Standard Training Program who completed the 26-week CTP and daily self-monitoring surveys, as well as full mental health assessments at pre-training (i.e., starting the CTP) and pre-deployment (i.e., ~2 weeks prior to deployment to the field). Symptoms of alcohol use disorder, generalized anxiety disorder, major depressive disorder, panic disorder, and posttraumatic stress disorder were assessed. Changes in mental health disorder symptom reporting from pre-training to pre-deployment were calculated. Spearman’s rank correlations were estimated for number of daily surveys completed and change in mental health disorder symptom scores between pre-training and pre-deployment.ResultsThere were statistically significant inverse relationships between number of daily surveys completed and number of mental health disorder symptoms reported; specifically, cadets who completed more daily surveys during CTP reported fewer symptoms of alcohol use disorder, generalized anxiety disorder, major depressive disorder, panic disorder, and posttraumatic stress disorder.ConclusionAn inverse correlation between number of daily surveys completed and mental health disorder symptom scores indicated that participation in daily mental health monitoring was associated with improvements in self-reported mental health disorder symptoms between pre-training and pre-deployment. Regular self-monitoring of mental health disorder symptoms may help to mitigate mental health challenges among RCMP cadets and officers.

Research on fish cognition provides strong evidence that fish are endowed with high level cognitive skills. However, most studies on cognitive flexibility and generalization abilities, two key adaptive traits for captive animals, focused on model species, and farmed fish received too little attention. Environmental enrichment was shown to improve learning abilities in various fish species, but its influence on cognitive flexibility and generalization abilities is still unknown. We studied farmed rainbow trout (Oncorhynchus mykiss) as an aquaculture model to study how environmental enrichment impacts their cognitive abilities. Using an operant conditioning device, allowing the expression of a motivated choice, we measured fish cognitive flexibility with serial reversal learning tests, after a successful acquisition phase based on two colors discrimination (2-alternative forced choice, 2-AFC), and their ability to generalize a rewarded color to any shape. Eight fish were divided into two groups: Condition E (fish reared from fry stages under enriched conditions with plants, rocks and pipes for ~9 months); Condition B (standard barren conditions). Only one fish (condition E) failed in the habituation phase of the device and one fish (condition B) failed in the 2-AFC task. We showed that after a successful acquisition phase in which the fish correctly discriminated two colors, they all succeeded in four reversal learnings, supporting evidence for cognitive flexibility in rainbow trout. They were all successful in the generalization task. Interestingly, fish reared in an enriched environment performed better in the acquisition phase and in the reversal learning (as evidenced by fewer trials needed to reach the learning criterion), but not in the generalization task. We assume that color-based generalization may be a simpler cognitive process than discriminative learning and cognitive flexibility, and does not seem to be influenced by environmental conditions. Given the small number of individuals tested, our results may be considered as first insights into cognitive flexibility in farmed fish using an operant conditioning device, but they pave the way for future studies. We conclude that farming conditions should take into account the cognitive abilities of fish, in particular their cognitive flexibility, by allowing them to live in an enriched environment.

IntroductionThe use of noninvasive biomarkers may avoid the need for liver biopsy (LB) and could guide immunosuppression adjustment in liver transplantation (LT). The aims of this study were: to confirm the predictive and diagnostic capacity of plasmatic expression of miR-155-5p, miR-181a-5p, miR-122-5p and CXCL-10 for assessing T-cell mediated rejection (TCMR) risk; to develop a score based on a panel of noninvasive biomarkers to predict graft rejection risk and to validate this score in a separate cohort.MethodsA prospective, observational study was conducted with a cohort of 79 patients followed during the first year after LT. Plasma samples were collected at predetermined time points for the analysis of miRNAs and the CXCL-10. Patients with LFTs abnormalities were submitted to a LB to rule out rejection, assessing previous and concurrent expression of the biomarkers to evaluate their predictive and diagnostic ability. Information from 86 patients included in a previous study was collected and used as a validation cohort.ResultsTwenty-four rejection episodes were diagnosed in 22 patients. Plasmatic CXCL-10 concentration and the expression of the three miRNAs were significantly elevated prior to and at the moment of the diagnosis of rejection. We developed a logistic model for rejection prediction and diagnosis, which included CXCL-10, miR-155-5p and miR-181a-5p. The area under the ROC curve (AUROC) for rejection prediction was 0.975 (79.6% sensitivity, 99.1% specificity, 90,7% PPV; 97.7% NPV; 97.1% correctly classified) and 0.99 for diagnosis (87.5% sensitivity, 99.5% specificity, 91.3% PPV; 99.3% NPV; 98.9% correctly classified). In the validation cohort (n=86; 14 rejections), the same cut-off points were used obtaining AUROCs for rejection prediction and diagnosis of 0.89 and 0.92 respectively. In patients with graft dysfunction in both cohorts the score could discriminate those with rejection regarding other causes with an AUROC of 0.98 (97.3% sensitivity, 94.1%specificity).ConclusionThese results suggest that the clinical implementation of the monitoring of this noninvasive plasmatic score may allow the prediction and diagnosis of rejection and identify patients with graft dysfunction due to rejection, helping with a more efficient guide for immunosuppressive therapy adjustment. This finding warrants the development of prospective biomarker-guided clinical trials.

The strength of the affective priming effect is influenced by various factors, including the duration of the prime. Surprisingly, short-duration primes that are around the threshold for conscious awareness typically result in stronger effects compared to long-duration primes. The misattribution effect theory suggest that subliminal primes do not provide sufficient cognitive processing time for the affective feeling to be attributed to the prime. Instead, the neutral target being evaluated is credited for the affective experience. In everyday social interactions, we shift our gaze from one face to another, typically contemplating each face for only a few seconds. It is reasonable to assume that no affective priming takes place during such interactions. To investigate whether this is indeed the case, participants were asked to rate the valence of faces displayed one by one. Each face image simultaneously served as both a target (primed by the previous trial) and a prime (for the next trial). Depending on the participant’s response time, images were typically displayed for about 1–2 s. As predicted by the misattribution effect theory, neutral targets were not affected by positive affective priming. However, non-neutral targets showed a robust priming effect, with emotional faces being perceived as even more negative or positive when the previously seen face was emotionally congruent. These results suggest that a “correct attribution effect” modulates how we perceive faces, continuously impacting our social interactions. Given the importance of faces in social communication, these findings have wide-ranging implications.

BackgroundRoyal Canadian Mounted Police (RCMP) officers experience an elevated risk for mental health disorders due to inherent work-related exposures to potentially psychologically traumatic events and occupational stressors. RCMP officers also report high levels of stigma and low levels of intentions to seek mental health services. In contrast, very little is known about the levels of mental health knowledge and stigma of RCMP cadets starting the Cadet Training Program (CTP). The current study was designed to: (1) obtain baseline levels of mental health knowledge, stigma against peers in the workplace, and service use intentions in RCMP cadets; (2) determine the relationship among mental health knowledge, stigma against peers in the workplace, and service use intentions among RCMP cadets; (3) examine differences across sociodemographic characteristics; and (4) compare cadets to a sample of previously surveyed serving RCMP.MethodsParticipants were RCMP cadets (n = 772) starting the 26-week CTP. Cadets completed questionnaires assessing mental health knowledge, stigma against coworkers with mental health challenges, and mental health service use intentions.ResultsRCMP cadets reported statistically significantly lower levels of mental health knowledge (d = 0.233) and stigma (d = 0.127), and higher service use intentions (d = 0.148) than serving RCMP (all ps

IntroductionThe particularities of the ocular immune environment and its barrier protection in the context of infection are not well elucidated. The apicomplexan parasite Toxoplasma gondii is one of the pathogens successfully crossing this barrier and establishing chronic infection in retinal cells.MethodsAs a first approach, we studied the initial cytokine network in vitro in four human cell lines: Retinal pigmented epithelial (RPE), microglial, astrocytic and Müller cells. Furthermore, we looked at the consequences of retinal infection on the integrity of the outer blood-retina barrier (oBRB). We particularly focused on the roles of type I and type III interferons, (IFN-β and IFN-λ). Especially IFN-λ is known for its significant role in barrier defense. However, its effect on the retinal barrier or T. gondii infection remains unexplored, unlike IFN-γ, which has been extensively studied in this context.Results and DiscussionHere, we show that stimulation with type I and III interferons did not limit parasite proliferation in retinal cells we tested. However, IFN-β and IFN-γ strongly induced inflammatory or cell-attracting cytokine production, whereas IFN-λ1 showed less inflammatory activity. Concomitant T. gondii infection influenced these cytokine patterns, distinctly depending on the parasite strain. Interestingly, all these cells could be stimulated to produce IFN-λ1. Using an in vitro oBRB model based on RPE cells, we observed that interferon stimulation strengthened membrane localization of the tight junction protein ZO-1 and enhanced their barrier function, in a STAT1-independent manner.ConclusionTogether, our model shows how T. gondii infection shapes the retinal cytokine network and barrier function, and demonstrates the role of type I and type III interferons in these processes.

The evolutionary emergence of the primitive gut in Metazoa is one of the decisive events that conditioned the major evolutionary transition, leading to the origin of animal development. It is thought to have been induced by the specification of the endomesoderm (EM) into the multicellular tissue and its invagination (i.e., gastrulation). However, the biochemical signals underlying the evolutionary emergence of EM specification and gastrulation remain unknown. Herein, we find that hydrodynamic mechanical strains, reminiscent of soft marine flow, trigger active tissue invagination/gastrulation or curvature reversal via a Myo-II-dependent mechanotransductive process in both the metazoan Nematostella vectensis (cnidaria) and the multicellular choanoflagellate Choanoeca flexa. In the latter, our data suggest that the curvature reversal is associated with a sensory-behavioral feeding response. Additionally, like in bilaterian animals, gastrulation in the cnidarian Nematostella vectensis is shown to participate in the biochemical specification of the EM through mechanical activation of the β-catenin pathway via the phosphorylation of Y654-βcatenin. Choanoflagellates are considered the closest living relative to metazoans, and the common ancestor of choanoflagellates and metazoans dates back at least 700 million years. Therefore, the present findings using these evolutionarily distant species suggest that the primitive emergence of the gut in Metazoa may have been initiated in response to marine mechanical stress already in multicellular pre-Metazoa. Then, the evolutionary transition may have been achieved by specifying the EM via a mechanosensitive Y654-βcatenin dependent mechanism, which appeared during early Metazoa evolution and is specifically conserved in all animals.

IntroductionPoor responder patients remain a challenge in assisted reproductive technologies. The “short agonist stop” (SAS) stimulation protocol uses a double stimulation (flare up effect with the gonadotropin-releasing hormone (GnRH) agonist (GnRH-a) then gonadotropins) associated with a less strenuous blockage (discontinuation of GnRH-a) to favor follicular recruitment in order to obtain a better ovarian response. This study aims to compare the number of oocytes obtained after a SAS stimulation protocol with those obtained after the previous stimulation protocol, in the same women, with poor ovarian response (POR) diagnosed according to the POSEIDON criteria.DesignThis therapeutic observational retrospective cohort from 2018 to 2022, with a case-control evaluation compared with the same patients’ previous performance, included women with POR undergoing IVF with SAS stimulation protocol. The primary outcome was the number of total oocytes recovered and secondary outcomes were the numbers of mature oocytes, total embryos observed at day 2 and usable cleaved embryos and blastocysts (day 5/6).Results63 patients with SAS and previous cycles were included. In the SAS group, the mean number of oocytes was significantly higher: 7.3 vs 5.7, p=0.018 in comparison with the previous attempt. So was the number of mature oocytes (5.8 vs 4.1, p=0.032) and the total mean number of embryos obtained at day 2 (4.1 versus 2.7, p=0.016). The SAS stimulation generated 84 usable embryos: 57 cleaved embryos and 27 blastocysts. The mean number of usable embryos was similar in both groups (1.64 vs 1.31, respectively, p=0.178). In total, out of 63 patients, after the SAS protocol, and subsequent embryo transfers (fresh and frozen, n=54), 9 patients had ongoing pregnancies and no miscarriage occurred. The cumulative ongoing pregnancy rate (cOPR) after the SAS protocol was 14.3% (9/63) per oocyte pick-up and 16.7% (9/54) per transfer.ConclusionSAS stimulation is a short and original protocol strengthening the therapeutic arsenal of poor responders, that may offer promising results for those patients with low prognosis and previous failed IVF. Results must be confirmed with a randomized controlled trial.

Epigenetic research in post-traumatic stress disorder (PTSD) is essential, given that environmental stressors and fear play such a crucial role in its development. As such, it may provide a framework for understanding individual differences in the prevalence of the disorder and in treatment response. This paper reviews the epigenetic markers associated with PTSD and its treatment, including candidate genes and epigenome-wide studies. Because the etiopathogenesis of PTSD rests heavily on learning and memory, we also draw upon animal neuroepigenetic research on the acquisition, update and erasure of fear memory, focusing on the mechanisms associated with memory reconsolidation. Reconsolidation blockade (or impairment) treatment in PTSD has been studied in clinical trials and, from a neurological perspective, may hold promise for identifying epigenetic markers of successful therapy. We conclude this paper by discussing several key considerations and challenges in epigenetic research on PTSD in humans.

In agricultural landscapes, forest herbs live in small, spatially isolated forest patches. For their long-term survival, their populations depend on animals as genetic linkers that provide pollen- or seed-mediated gene flow among different forest patches. However, whether insect pollinators serve as genetic linkers among spatially isolated forest herb populations in agricultural landscapes remains to be shown. Here, we used population genetic methods to analyze: (A) the genetic diversity and genetic differentiation of populations of two common, slow-colonizing temperate forest herb species [Polygonatum multiflorum (L.) All. and Anemone nemorosa L.] in spatially isolated populations within three agricultural landscapes in Germany and Sweden and (B) the movement activity of their most relevant associated pollinator species, i.e., the bumblebee Bombus pascuorum (Scopoli, 1,763) and the hoverfly Melanostoma scalare (Fabricus, 1,794), respectively, which differ in their mobility. We tested whether the indicated pollinator movement activity affected the genetic diversity and genetic differentiation of the forest herb populations. Bumblebee movement indicators that solely indicated movement activity between the forest patches affected both genetic diversity and genetic differentiation of the associated forest herb P. multiflorum in a way that can be explained by pollen-mediated gene flow among the forest herb populations. In contrast, movement indicators reflecting the total movement activity at a forest patch (including within-forest patch movement activity) showed unexpected effects for both plant-pollinator pairs that might be explained by accelerated genetic drift due to enhanced sexual reproduction. Our integrated approach revealed that bumblebees serve as genetic linkers of associated forest herb populations, even if they are more than 2 km apart from each other. No such evidence was found for the forest associated hoverfly species which showed significant genetic differentiation among forest patches itself. Our approach also indicated that a higher within-forest patch movement activity of both pollinator species might enhance sexual recruitment and thus diminishes the temporal buffer that clonal growth provides against habitat fragmentation effects.

Objectives: No consensus exists about the doses of analgesics, sedatives, anesthetics, and paralytics used in critically ill neonates. Large-scale, detailed pharmacoepidemiologic studies of prescription practices are a prerequisite to future research. This study aimed to describe the detailed prescriptions of these drug classes in neonates hospitalized in neonatal intensive care units (NICU) from computerized prescription records and to compare prescriptions by gestational age.Materials and Methods: We included all neonates requiring intensive care in 30 French level III units from 2014 through 2020 with a computerized prescription for an analgesic, sedative, anesthetic, or paralytic agent. We described frequencies of prescription, methods of administration, concomitant drug prescriptions, and dosing regimen, and compared them across gestational ages.Results: Among 65,555 neonates, 29,340 (44.8%) were prescribed at least one analgesic (acetaminophen in 37.2% and opioids in 17.8%), sedative (9.8%), anesthetic (8.5%), and/or paralytic agent (1%). Among preterm infants born before 28 weeks, 3,771/4,283 (88.0%) were prescribed at least one of these agents: 69.7% opioids, 41.2% sedatives, 32.5% anesthetics, and 5.8% paralytics. The most frequently prescribed agents were sufentanil (in 10.3% of neonates) and morphine (in 8.0% of neonates) for opioids, midazolam (9.3%) for sedatives, ketamine (5.7%) and propofol (3.3%) for anesthetics. In most neonates, opioids and sedatives were prescribed as continuous infusion, whereas anesthetics were prescribed as single doses. Opioids, sedatives and paralytics were mostly prescribed in association with another agent. Doses varied significantly by gestational age but within a limited range. Gestational age was inversely related to the frequency, cumulative dose and duration of prescriptions. For example, morphine prescriptions showed median (IQR) cumulative doses of 2601 (848–6750) vs. 934 (434–2679) µg/kg and median (IQR) durations of 7 (3–15) vs. 3 (2–5) days in infants born

Myotonic dystrophy type 1 (DM1) is the most prevalent inherited neuromuscular dystrophy in adults. It is a multisystem disease with cardiac manifestations. Whilst these are well-defined in adults, there are scarce published data in the pediatric population. This study aimed to investigate the yield and progression of cardiac disease in pediatric DM1 patients, focusing on congenital DM1 (cDM1).MethodsA retrospective observational study of all pediatric DM1 patients referred to our center (December 2000-November 2020) was conducted. Patients were classified into DM1 forms according to age of symptom onset and disease severity. Patients underwent clinical and cardiac evaluation with 12-lead ECG, transthoracic echocardiography and 24-h ECG Holter monitoring.Results67 DM1 pediatric patients were included: 56 (83.6%) cDM1 and 11 (16.4%) non-cDM1. Median follow-up time of cDM1 patients was 8.0 [3.25–11.0] years. 49 (87.5%) cDM1 patients had baseline 12-lead ECG and 44 (78.6%) had a follow-up 12-lead-ECG, with a median follow-up time from diagnosis to baseline ECG of 2.8 [1.0–8.5] years and to follow-up ECG of 10.9 [5.7–14.2] years. Overall, 43 (87.8%) presented ECG abnormalities, most commonly in the form of asymptomatic conduction disease (n = 23, 46.9%), of which 21 (42.9%) had first degree atrioventricular block (1st AVB). There was an increase of prevalence from baseline to follow-up ECG in low QRS voltage (16.7%), poor R wave progression (13.9%), abnormal repolarisation (11.9%) and 1st AVB (7.6%). one patient (1.8%) underwent pacemaker implantation for syncope in the context of progressive conduction disease. No patients developed left ventricular systolic dysfunction. 4 (7.1%) cDM1 patients died during follow up, including three who died suddenly with no clear cause of death.ConclusionsThis study is the first to analyse the prevalence and progression of ECG abnormalities in cDM1 pediatric patients. The high prevalence of abnormal findings, progressive changes and number of potentially associated events (1 pacemaker implantation and 3 unexplained sudden deaths) stresses the importance of systematic and continued cardiac evaluation of these patients.

The use of extracellular vesicles (EVs) is emerging as a promising acellular approach for bone regeneration, overcoming translational hurdles associated with cell-based therapies. Despite their potential, EVs short half-life following systemic administration hinders their therapeutic efficacy. EVs have been reported to bind to extracellular matrix (ECM) proteins and play an essential role in matrix mineralisation. Chitosan and collagen type I are naturally-derived pro-osteogenic biomaterials, which have been demonstrated to control EV release kinetics. Therefore, this study aimed to develop an injectable ECM-mimetic hydrogel capable of controlling the release of osteoblast-derived EVs to promote bone repair. Pure chitosan hydrogels significantly enhanced compressive modulus (2.48-fold) and osteogenic differentiation (3.07-fold), whilst reducing gelation times (2.09-fold) and proliferation (2.7-fold) compared to pure collagen gels (p ≤ 0.001). EV release was strongly associated with collagen concentration (R2 > 0.94), where a significantly increased EV release profile was observed from chitosan containing gels using the CD63 ELISA (p ≤ 0.001). Hydrogel-released EVs enhanced human bone marrow stromal cells (hBMSCs) proliferation (1.12-fold), migration (2.55-fold), and mineralisation (3.25-fold) compared to untreated cells (p ≤ 0.001). Importantly, EV-functionalised chitosan-collagen composites significantly promoted hBMSCs extracellular matrix mineralisation when compared to the EV-free gels in a dose-dependent manner (p ≤ 0.001). Taken together, these findings demonstrate the development of a pro-osteogenic thermosensitive chitosan-collagen hydrogel capable of enhancing the therapeutic efficacy of osteoblast-derived EVs as a novel acellular tool for bone augmentation strategy.

Risk-taking behaviors in adolescents have traditionally been analyzed from a psychopathological approach, with an excessive emphasis on their potential costs. From evolutionary theory we propose that risk-taking behaviors can be means through which adolescents obtain potential benefits for survival and reproduction. The present study analyses sex differences in three contexts of risk (i.e., risk propensity, expected benefits and risk perception) in the evolutionary specific domains and the predictive value of these domains over risk-taking behaviors, separately in female and male adolescents. 749 adolescents (females = 370) valued their risk perception, expected benefits and risk propensity through the Evolutionary Domain-Specific Risk Scale, as well as their engagement in risk-taking behaviors through the Risky Behavior Questionnaire. Male adolescents showed lower risk perception in two evolutionary domains, expected higher benefits in two other domains and showed higher risk propensity in six domains. Female adolescents showed lower risk perception in two domains. Additionally, risk perception, expected benefits and risk propensity in the evolutionary domains predicted the engagement in risk-taking behaviors in male adolescents, whereas in female adolescents only expected benefits and risk propensity showed a predictive effect over risk-taking behaviors. These results suggest the potential role of evolutionary mechanisms on risk-taking behaviors in adolescents. Results have practical implications for interventions programs aimed at reducing risk-taking behaviors. In addition to considering sex differences, intervention programs should consider alternative behaviors through which adolescents can reach their evolutionary goals, and handle the risks related to those behaviors that cannot be replaced but have potential benefits for adolescents.

Purpose: This paper describes women’s opinions of the attributes of the ideal body image program to inform the design, development, and implementation of future programs for those diagnosed with breast cancer.Methods: Deductive-inductive content analysis of semi-structured interviews with 26 women diagnosed with breast cancer (mean age = 55.96 years; mean time since diagnosis = 2.79 years) was performed.Findings: Participants’ opinions regarding the ideal body image program are summarized into five themes, mapping the where (community-based, hospital-based, or online), when (across the cancer continuum or at specific points), how (peer-led programs, professional help, events, presentations/workshops, resources, support groups), what (self-care, counseling and education for one self, education for others, support for addressing sexuality/sexual health concerns, and concealing treatment-related changes), and who (team approach or delivered by women, health professionals, make-up artists).Conclusion: This study provides useful data on what women believe are the attributes of the ideal body image program, which can contribute to efforts aimed at developing and delivering body image programs for women diagnosed with breast cancer that prioritize their needs and preferences.

Extracellular Vesicles (EVs) are considered promising nanoscale therapeutics for bone regeneration. To date, EVs are typically procured from cells on 2D tissue culture plastic, an artificial environment that limits cell growth and does not replicate in situ biochemical or biophysical conditions. This study investigated the potential of 3D printed titanium scaffolds coated with hydroxyapatite to promote the therapeutic efficacy of osteoblast-derived EVs. Ti6Al4V titanium scaffolds with different pore sizes (500 and 1000 µm) and shapes (square and triangle) were fabricated by selective laser melting. A bone-mimetic nano-needle hydroxyapatite (nnHA) coating was then applied. EVs were procured from scaffold-cultured osteoblasts over 2 weeks and vesicle concentration was determined using the CD63 ELISA. Osteogenic differentiation of human bone marrow stromal cells (hBMSCs) following treatment with primed EVs was evaluated by assessing alkaline phosphatase activity, collagen production and calcium deposition. Triangle pore scaffolds significantly increased osteoblast mineralisation (1.5-fold) when compared to square architectures (P ≤ 0.001). Interestingly, EV yield was also significantly enhanced on these higher permeability structures (P ≤ 0.001), in particular (2.2-fold) for the larger pore structures (1000 µm). Furthermore osteoblast-derived EVs isolated from triangular pore scaffolds significantly increased hBMSCs mineralisation when compared to EVs acquired from square pore scaffolds (1.7-fold) and 2D culture (2.2-fold) (P ≤ 0.001). Coating with nnHA significantly improved osteoblast mineralisation (>2.6-fold) and EV production (4.5-fold) when compared to uncoated scaffolds (P ≤ 0.001). Together, these findings demonstrate the potential of harnessing bone-mimetic culture platforms to enhance the production of pro-regenerative EVs as an acellular tool for bone repair.

Blastocystis is the most frequently isolated protozoan from human stool. Its role in human health is still debated, and a high prevalence was reported in irritable bowel syndrome (IBS) subjects, suggesting a potential link with microbiota. In the present study, we aimed to investigate prokaryotic and eukaryotic microbiota in both IBS-C (constipated) and healthy individuals. We recruited 35 IBS-C patients and 23 healthy subjects, from which 12 and 11 carried Blastocystis, respectively. We performed 16S and 18S rRNA high-throughput sequencing on feces. Whereas we did not observe differences between infected and non-infected controls, several phyla were significantly modified in IBS-C patients according to the presence of Blastocystis. Tenericutes phylum and Ruminococcaceae family were especially increased in Blastocystis carriers. Furthermore, colonization with Blastocystis was associated with discrete changes in the microbial eukaryome, particularly among the Fungi taxa. Depending on the group of patients considered, the mycobiota changes do not go in the same direction and seem more deleterious in the IBS-C group. These results encourage further in vivo and in vitro investigations concerning the role of Blastocystis in the gut environment.

Selfing (self-pollination) is the ultimate form of inbreeding, or mating among close relatives. Selfing can create yield loss when inbreeding depression, defined as a lower survival and reproduction of inbred relative to outbred progeny, is present. To determine the impact of selfing in alfalfa (Medicago sativa L.), we quantified the selfing rate of 32 alfalfa seed production fields located in three regions, namely, the Pacific Northwest (PNW), the Central Valley of California (CEV), and the Imperial Valley of California (IMP). Selfing rates (the proportion of selfed seeds) varied between 5.3 and 30% with an average of 12.2% over the 32 seed production fields. In both the parents and their progeny, we observed an excess of heterozygotes relative to Hardy–Weinberg expectations. We detected notable levels of inbreeding in parents (0.231 ± 0.007 parental inbreeding coefficient) and progeny (0.229 ± 0.005). There were a 15% decrease in the number of seeds per stem (seed set) and a 13% decline in the number of seeds per pod in selfed relative to outcrossed stems, but negligible inbreeding depression for pods per raceme and seed weight. The number of racemes on selfed stems increased significantly in fields with greater selfing rates, supporting the presence of geitonogamous or among flower selfing. Despite the significant level of inbreeding depression, seed set did not decrease in fields with higher selfing rates, where the greater number of racemes on the selfed stems increased the seed set. The effects of the field selfing rate on the seed yield metrics were mostly indirect with direct effects of the number of racemes per stem. Available data indicate that the majority of selfing in alfalfa is pollinator-mediated, and thus, eliminating selfing in alfalfa seed production would require the selection of self-incompatible varieties, which, by eliminating inbreeding depression, would provide a 15% potential increase in seed yield and an increase in future hay yield.

Background: International migration processes are some of the most important events of our time. Migrating implies a broad range of factors that affect integration, and which may be linked to radicalization. Host countries use different methods for the integration of migrants. The aim of this systematic review is to analyze intervention programs that aim at promoting social integration and preventing the radicalization of migrants, with the objective of studying actions carried out in the US, Canada, and Europe to this effect.Method: Worldwide known bibliographic databases (PsyCINFO, Sociological Abstracts, Psycarticles, Psychology Database, Medline, SCOPUS, and Google Scholar) were used to search studies published before January 2019 and which analyzed integration or radicalization prevention programs with migrants.Results: A total of 601 studies were screened, from which 18 met the inclusion criteria. The analysis of programs addressed to migrant women points to a decrease in loneliness and depression and an increase of migrants' perception of social support and self-esteem. Programs carried out in schools and families improve children's knowledge of their culture and that of others, increase their feelings of inclusion, and reduce their aggressiveness, stress, and anxiety. Language programs promote communication and employment search, as well as improve migrants' quality of life. One of the most effective activities included in these programs is to connect recently arrived migrants with local population and/or long-term residents. The latter act as mentors and teachers, helping recently arrived migrants understand resources and to be more integrated in the new country, as well as reducing discrimination from the local population.Conclusions: The review concluded the importance of intervention programs for integration, migrants' quality of life, prevention of extreme behaviors, and intercultural cohabitation. Future programs must be more detailed regarding participants' information and carry out more comprehensive assessments.

Previous studies have found it is more difficult identifying an emotional expression displayed by an older than a younger face. It is unknown whether this is caused by age-related changes such as wrinkles and folds interfering with perception, or by the aging of facial muscles, potentially reducing the ability of older individuals to display an interpretable expression. To discriminate between these two possibilities, participants attempted to identify facial expressions under different conditions. To control for the variables (wrinkles/folds vs facial muscles), we used Generative Adversarial Networks to make faces look older or younger. Based upon behavior data collected from 28 individuals, our model predicts that the odds of correctly identifying the expressed emotion of a face reduced 16.2% when younger faces (condition 1) are artificially aged (condition 3). Replacing the younger faces with natural old-looking faces (Condition 2), however, results in an even stronger effect (odds of correct identification decreased by 50.9%). Counterintuitively, making old faces (Condition 2) look young (Condition 4) results in the largest negative effect (odds of correct identification decreased by 74.8% compared with natural young faces). Taken together, these results suggest that both age-related decline in the facial muscles’ ability to express facial emotions and age-related physical changes in the face, explain why it is difficult to recognize facial expressions from older faces; the effect of the former, however, is much stronger than that of the latter. Facial muscle exercises, therefore, might improve the capacity to convey facial emotional expressions in the elderly.

Coastal areas impacted by high anthropogenic pressures typically display sediment contamination by polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HMs). Microbial-based bioremediation represents a promising strategy for sediment reclamation, yet it frequently fails due to poor knowledge of the diversity and dynamics of the autochthonous microbial assemblages and to the inhibition of the target microbes in the contaminated matrix. In the present study, we used an integrated approach including a detailed environmental characterization, high-throughput sequencing and culturing to identify autochthonous bacteria with bioremediation potential in the sediments of Bagnoli-Coroglio (Gulf of Naples, Mediterranean Sea), a coastal area highly contaminated by PAHs, aliphatic hydrocarbons and HMs. The analysis of the benthic prokaryotic diversity showed that the distribution of the dominant taxon (Gammaproteobacteria) was mainly influenced by PAHs, As, and Cd concentrations. The other abundant taxa (including Alphaproteobacteria, Deltaproteobacteria, Bacteroidetes, Acidobacteria, Actinobacteria, NB1-j, Desulfobacterota, and Myxococcota) were mainly driven by sediment grain size and by Cu and Cr concentrations, while the rare taxa (i.e., each contributing

Neurotransmitter expression is widely used as a criterion for classifying neurons. It was initially thought that neurons express a single type of neurotransmitter, a phenomenon commonly recognized as Dale's principle: “one neuron, one transmitter.” Consequently, the expression of a single neurotransmitter should determine stable and distinguishable neuronal characteristics. However, this notion has been largely challenged and increasing evidence accumulates supporting a different scenario: “one neuron, multiple neurotransmitters.” Single-cell transcriptomics provides an additional path to address coexpression of neurotransmitters, by investigating the expression of genes involved in the biosynthesis and transmission of fast-acting neuromodulators. Here, we study neuronal phenotypes based on the expression of neurotransmitters, at single-cell resolution, across different animal species representing distinct clades of the tree of life. We take advantage of several existing scRNAseq datasets and analyze them in light of neurotransmitter plasticity. Our results show that while most neurons appear to predominantly express a single type of neurotransmitter, a substantial number of neurons simultaneously expresses a combination of them, across all animal species analyzed.

Plants exhibit a wide array of floral forms and pollinators can act as agent of selection on floral traits. Two trends have emerged from recent reviews of pollinator-mediated selection in plants. First, pollinator-mediated selection on plant-level attractants such as floral display size is stronger than on flower-level attractant such as flower color. Second, when comparing plant species, distinct pollinators can exert different selection patterns on floral traits. In addition, many plant species are visited by a diverse array of pollinators but very few studies have examined selection by distinct pollinators. In the current study, we examined phenotypic selection on flower color and floral display size by three distinct bee species, the European honey bee, Apis mellifera, the common eastern bumble bee, Bombus impatiens, and the alfalfa leafcutting bee, Megachile rotundata, foraging on Medicago sativa. To estimate phenotypic selection by each bee species and for all bees combined simultaneously and on the same group of plants, we introduce a new method that combines pollinator visitation data to seed set and floral trait measurements data typical of phenotypic selection study. When comparing floral traits, all bee species selected on the number of racemes per stem and the number of stems per plant, two components of floral display size. However, only leafcutting bees selected on hue or flower color and only bumble bees selected on chroma or darkness of flowers. Selection on chroma occurred via correlational selection between chroma and number of open flowers per raceme and we examine how correlational selection may facilitate the evolution of flower color in plant populations. When comparing bee species, the three bee species exerted similar selection pattern on some floral traits but different patterns on other floral traits and differences in selection patterns were observed between flower-level and plant-level attractants. The trends detected were consistent with previous studies and we advocate the approach introduced here for future studies examining the impact of distinct pollinators on floral trait evolution.

This paper presents the first systematic case-control study of correlates of mass psychogenic illness (MPI) in an adolescent school population. MPI is generally construed as a dissociative phenomenon spread by social contagion to individuals who are prone to dissociation. We sought to test if the correlates of dissociative experiences most commonly proposed in the literature could predict caseness among students affected by episodes of mass psychogenic illness occurring in schools in Nepal. We assessed 194 cases and 190 controls (N = 384) of ages 11–18 years from 12 public schools. Cases and controls were comparable on all demographic variables, except for family configuration, with nuclear families more common among those affected. In bivariate comparisons, caseness was associated with childhood physical neglect and abuse, as well as living in nuclear families, peritraumatic dissociation, dissociative tendencies, and depressive and post-traumatic stress symptoms. Hypnotizability emerged as the strongest correlate of psychogenic illness among the cognitive and personality trait variables. However, in multivariable logistic regression, the correlates of dissociation did not predict caseness, suggesting that they do not adequately account for the phenomenon of mass psychogenic illness. An ad-hoc Classification and Regression Trees analysis showed that if an adolescent was highly hypnotizable and reported high rates of peritraumatic dissociative experiences, then there was a 73% probability of being a case in a mass psychogenic illness episode. Future studies involving other psychological, social and cultural factors, as well as school- and family-related factors are needed to understand the correlates of mass psychogenic illness and guide prevention and intervention.

Iron-reducing bacteria (IRB) are strongly involved in Fe cycling in surface environments. Transformation of Fe and associated trace elements is strongly linked to the reactivity of various iron minerals. Mechanisms of Fe (oxyhydr)oxides bio-reduction have been mostly elucidated with pure bacterial strains belonging to Geobacter or Shewanella genera, whereas studies involving mixed IRB populations remain scarce. The present study aimed to evaluate the iron reducing rates of IRB enriched consortia originating from complex environmental samples, when grown in presence of Fe (oxyhydr)oxides of different mineralogy. The abundances of Geobacter and Shewanella were assessed in order to acquire knowledge about the abundance of these two genera in relation to the effects of mixed IRB populations on kinetic control of mineralogical Fe (oxyhydr)oxides reductive dissolution. Laboratory experiments were carried out with two freshly synthetized Fe (oxyhydr)oxides presenting contrasting specific surfaces, and two defined Fe-oxides, i.e., goethite and hematite. Three IRB consortia were enriched from environmental samples from a riverbank subjected to cyclic redox oscillations related to flooding periods (Decize, France): an unsaturated surface soil, a flooded surface soil and an aquatic sediment, with a mixture of organic compounds provided as electron donors. The consortia could all reduce iron-nitrilotriacetate acid (Fe(III)-NTA) in 1–2 days. When grown on Fe (oxyhydr)oxides, Fe solubilization rates decreased as follows: fresh Fe (oxyhydr)oxides > goethite > hematite. Based on a bacterial rrs gene fingerprinting approach (CE-SSCP), bacterial community structure in presence of Fe(III)-minerals was similar to those of the site sample communities from which they originated but differed from that of the Fe(III)-NTA enrichments. Shewanella was more abundant than Geobacter in all cultures. Its abundance was higher in presence of the most efficiently reduced Fe (oxyhydr)oxide than with other Fe(III)-minerals. Geobacter as a proportion of the total community was highest in the presence of the least easily solubilized Fe (oxyhydr)oxides. This study highlights the influence of Fe mineralogy on the abundance of Geobacter and Shewanella in relation to Fe bio-reduction kinetics in presence of a complex mixture of electron donors.

Traditionally, reference genomes in crop species rely on the assembly of one accession, thus occulting most of intraspecific diversity. However, rearrangements, gene duplications, and transposable element content may have a large impact on the genomic structure, which could generate new phenotypic traits. Comparing two Brassica rapa genomes recently sequenced and assembled using long-read technology and optical mapping, we investigated structural variants and repetitive content between the two accessions and genome size variation among a core collection. We explored the structural consequences of the presence of large repeated sequences in B. rapa ‘Z1’ genome vs. the B. rapa ‘Chiifu’ genome, using comparative genomics and cytogenetic approaches. First, we showed that large genomic variants on chromosomes A05, A06, A09, and A10 are due to large insertions and inversions when comparing B. rapa ‘Z1’ and B. rapa ‘Chiifu’ at the origin of important length differences in some chromosomes. For instance, lengths of ‘Z1’ and ‘Chiifu’ A06 chromosomes were estimated in silico to be 55 and 29 Mb, respectively. To validate these observations, we compared using fluorescent in situ hybridization (FISH) the two A06 chromosomes present in an F1 hybrid produced by crossing these two varieties. We confirmed a length difference of 17.6% between the A06 chromosomes of ‘Z1’ compared to ‘Chiifu.’ Alternatively, using a copy number variation approach, we were able to quantify the presence of a higher number of rDNA and gypsy elements in ‘Z1’ genome compared to ‘Chiifu’ on different chromosomes including A06. Using flow cytometry, the total genome size of 12 Brassica accessions corresponding to a B. rapa available core collection was estimated and revealed a genome size variation of up to 16% between these accessions as well as some shared inversions. This study revealed the contribution of long-read sequencing of new accessions belonging to different cultigroups of B. rapa and highlighted the potential impact of differential insertion of repeat elements and inversions of large genomic regions in genome size intraspecific variability.

Besides the main cortical inputs to the basal ganglia, via the corticostriatal projection, there is another input via the corticosubthalamic projection (CSTP), terminating in the subthalamic nucleus (STN). The present study investigated and compared the CSTPs originating from the premotor cortex (PM) or the primary motor cortex (M1) in two groups of adult macaque monkeys. The first group includes six intact monkeys, whereas the second group was made up of four monkeys subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication producing Parkinson’s disease (PD)-like symptoms and subsequently treated with an autologous neural cell ecosystem (ANCE) therapy. The CSTPs were labeled with the anterograde tracer biotinylated dextran amine (BDA), injected either in PM or in M1. BDA-labeled axonal terminal boutons in STN were charted, counted, and then normalized based on the number of labeled corticospinal axons in each monkey. In intact monkeys, the CSTP from PM was denser than that originating from M1. In two PD monkeys, the CSTP originating from PM or M1 were substantially increased, as compared to intact monkeys. In one other PD monkey, there was no obvious change, whereas the last PD monkey showed a decrease of the CSTP originating from M1. Interestingly, the linear relationship between CSTP density and PD symptoms yielded a possible dependence of the CSTP re-organization with the severity of the MPTP lesion. The higher the PD symptoms, the larger the CSTP densities, irrespective of the origin (from both M1 or PM). Plasticity of the CSTP in PD monkeys may be related to PD itself and/or to the ANCE treatment.

The human brain is tuned to recognize emotional facial expressions in faces having a natural upright orientation. The relative contributions of featural, configural, and holistic processing to decision-making are as yet poorly understood. This study used a diffusion decision model (DDM) of decision-making to investigate the contribution of early face-sensitive processes to emotion recognition from physiognomic features (the eyes, nose, and mouth) by determining how experimental conditions tapping those processes affect early face-sensitive neuroelectric reflections (P100, N170, and P250) of processes determining evidence accumulation at the behavioral level. We first examined the effects of both stimulus orientation (upright vs. inverted) and stimulus type (photographs vs. sketches) on behavior and neuroelectric components (amplitude and latency). Then, we explored the sources of variance common to the experimental effects on event-related potentials (ERPs) and the DDM parameters. Several results suggest that the N170 indicates core visual processing for emotion recognition decision-making: (a) the additive effect of stimulus inversion and impoverishment on N170 latency; and (b) multivariate analysis suggesting that N170 neuroelectric activity must be increased to counteract the detrimental effects of face inversion on drift rate and of stimulus impoverishment on the stimulus encoding component of non-decision times. Overall, our results show that emotion recognition is still possible even with degraded stimulation, but at a neurocognitive cost, reflecting the extent to which our brain struggles to accumulate sensory evidence of a given emotion. Accordingly, we theorize that: (a) the P100 neural generator would provide a holistic frame of reference to the face percept through categorical encoding; (b) the N170 neural generator would maintain the structural cohesiveness of the subtle configural variations in facial expressions across our experimental manipulations through coordinate encoding of the facial features; and (c) building on the previous configural processing, the neurons generating the P250 would be responsible for a normalization process adapting to the facial features to match the stimulus to internal representations of emotional expressions.

Besides classic tobacco and alcohol risk factors, human papillomavirus (HPV) plays a role in the development of a subset of head and neck squamous cell carcinomas (HNSCCs), and notably oropharynx squamous cell carcinomas (OPSCCs). HPV-induced OPSCCs have a different biological behavior and a better prognosis compared to non-HPV-induced OPSCCs and the eighth-edition TNM classification now separates these two entities. Therefore, determining the HPV status of patients with OPSCC is now essential for treatment, prognosis, and development of clinical trials. In this review, after reminding essential steps of HPV implication in the cell cycle, we describe the existing tools that are currently feasible in routine practice according to facilities available in health structures, with their benefits and drawbacks: HPV PCR, E6/E7 mRNA RT-PCR, E6/E7 mRNA in situ hybridization, HPV DNA in situ hybridization, and P16 immunochemistry. Besides these traditional HPV detection tools, novel diagnostic approaches are being evaluated for HPV-induced OPSCC “ultrastaging.” E6 humoral response and ddPCR-detecting HPVct DNA are two techniques performed on blood and are therefore non-invasive. Baseline E6 humoral levels could have a prognostic value, and HPVct DNA could be helpful for HPV OPSCC recurrence monitoring. At last, next-generation sequencing (NGS)-based “capture HPV” is a technique feasible on biopsies and circulating DNA material. It helps characterize HPV integration status and sites, and it could define prognostic subgroups in HPV-induced OPSCC. These novel precision detection tools could be further integrated in the care of patients with HPV-induced OPSCC.

Combining results from multiple imaging techniques (i.e., multi-modal imaging) through image registration can result in the better characterization of joint tissue characteristics. In the context of inflammatory arthritis conditions, high-resolution peripheral quantitative computed tomography (HR-pQCT) provides excellent bone contrast while magnetic resonance imaging (MRI) provides superior contrast and resolution of soft tissue and inflammatory characteristics. Superimposing these imaging results upon each other provides a robust characterization of the joint. In a preliminary study of nine rheumatoid arthritis (RA) participants in clinical remission, we acquired HR-pQCT and MR images of their 2nd and 3rd metacarpophalangeal (MCP) joints at two timepoints 6 months apart. We present the benefits of a multi-modal imaging approach, in which we demonstrate the ability to localize regions of inflammation with subtle changes in bone erosion volume. Using HR-pQCT and MRI to visualize bone damage and inflammation, respectively, will improve our understanding of the impact that subclinical inflammation has on bone damage progression, and demonstrating if bone repair occurs where inflammation is resolved. The presented multi-modal imaging technique has the potential to study the progression of bone damage in relation to inflammation that otherwise would not be possible with either imaging technique alone. The multi-modal image registration technique will be helpful to understanding the development and pathogenesis of RA-associated bone erosions. Additionally, multi-modal imaging may provide a technique to probe the tissue-level changes that occur as a result of treatment regimes.

Indian fruit bats, flying fox Pteropus medius was identified as an asymptomatic natural host of recently emerged Nipah virus, which is known to induce a severe infectious disease in humans. The absence of P. medius genome sequence presents an important obstacle for further studies of virus–host interactions and better understanding of mechanisms of zoonotic viral emergence. Generation of the high-quality genome sequence is often linked to a considerable effort associated to elevated costs. Although secondary scaffolding methods have reduced sequencing expenses, they imply the development of new tools for the integration of different data sources to achieve more reliable sequencing results. We initially sequenced the P. medius genome using the combination of Illumina paired-end and Nanopore sequencing, with a depth of 57.4x and 6.1x, respectively. Then, we introduced the novel scaff2link software to integrate multiple sources of information for secondary scaffolding, allowing to remove the association with discordant information among two sources. Different quality metrics were next produced to validate the benefits from secondary scaffolding. The P. medius genome, assembled by this method, has a length of 1,985 Mb and consists of 33,613 contigs and 16,113 scaffolds with an NG50 of 19 Mb. At least 22.5% of the assembled sequences is covered by interspersed repeats already described in other species and 19,823 coding genes are annotated. Phylogenetic analysis demonstrated the clustering of P. medius genome with two other Pteropus bat species, P. alecto and P. vampyrus, for which genome sequences are currently available. SARS-CoV entry receptor ACE2 sequence of P. medius was 82.7% identical with ACE2 of Rhinolophus sinicus bats, thought to be the natural host of SARS-CoV. Altogether, our results confirm that a lower depth of sequencing is enough to obtain a valuable genome sequence, using secondary scaffolding approaches and demonstrate the benefits of the scaff2link application. The genome sequence is now available to the scientific community to (i) proceed with further genomic analysis of P. medius, (ii) to characterize the underlying mechanism allowing Nipah virus maintenance and perpetuation in its bat host, and (iii) to monitor their evolutionary pathways toward a better understanding of bats’ ability to control viral infections.

It is known that cancer stem cells (CSCs) with the largest proliferative capacity survive the anoxic and/or ischemic conditions present inside tumorous tissue. In this study we test whether normal stem cells can survive under the same conditions due to cancer cell-like metabolic adaptations. We cultivated a CD34+ population with a majority of hematopoietic progenitors, and a CD34+CD38lowCD133+CD90+CD45RA− population, highly enriched in hematopoietic stem cells (HSCs), under anoxic, anoxic/aglycemic (“ischemia-like”), or physiological conditions (3% O2). Results showed, despite a reduction in total cell fold expansion proportionate to the decrease in O2 concentration; CD34+ cells, aldehyde dehydrogenase-expressing primitive cells, and committed progenitors expanded, even in anoxia. Interestingly, under ischemia-like conditions, stem and CD34+ cell populations are maintained at day-0 level. Cell-cycle analysis further revealed an accumulation of cells in the G0/G1 phase in anoxia or anoxia/aglycemia, with a fraction of cells (~40%) actively cycling (SG2M phases). Also stem cell analysis showed that in these conditions a long-term Scid Repopulating activity was equal to that found with 3% O2. In addition stem cells with the highest proliferative capacity were maintained in anoxia/aglycemia and in anoxia. The estimated ATP profile, active mitochondrial content, and succinate accumulation are indicative of anaerobic mitochondrial respiration in both HSCs and CD34+ progenitors under ischemia-like conditions. We demonstrate here that primitive hematopoietic cells show similar metabolic flexibility to CSCs, allowing them to survive a lack of O2 and O2/glucose. Our study reveals that this feature is not the consequence of malignant transformation, but an attribute of stemness.

The persistence of heavy metals (HMs) in the environment causes adverse effects to all living organisms; HMs accumulate along the food chain affecting different levels of biological organizations, from cells to tissues. HMs enter cells through transporter proteins and can bind to enzymes and nucleic acids interfering with their functioning. Strategies used by microalgae to minimize HM toxicity include the biosynthesis of metal-binding peptides that chelate metal cations inhibiting their activity. Metal-binding peptides include genetically encoded metallothioneins (MTs) and enzymatically produced phytochelatins (PCs). A number of techniques, including genetic engineering, focus on increasing the biosynthesis of MTs and PCs in microalgae. The present review reports the current knowledge on microalgal MTs and PCs and describes the state of art of their use for HM bioremediation and other putative biotechnological applications, also emphasizing on techniques aimed at increasing the cellular concentrations of MTs and PCs. In spite of the broad metabolic and chemical diversity of microalgae that are currently receiving increasing attention by biotechnological research, knowledge on MTs and PCs from these organisms is still limited to date.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that affects selected cortical and spinal neuronal populations, leading to progressive paralysis and death. A growing body of evidences suggests that the disease may originate in the cerebral cortex and propagate in a corticofugal manner. In particular, transcranial magnetic stimulation studies revealed that ALS patients present with early cortical hyperexcitability arising from a combination of increased excitability and decreased inhibition. Here, we discuss the possibility that initial cortical circuit dysfunction might act as the main driver of ALS onset and progression, and review recent functional, imaging and transcriptomic studies conducted on ALS patients, along with electrophysiological, pathological and transcriptomic studies on animal and cellular models of the disease, in order to evaluate the potential cellular and molecular origins of cortical hyperexcitability in ALS.

The focus in this paper is on understanding the complex intersections between crises and memory politics in shaping conversations about citizenship through an examination of the two defining crises of our time: the global financial crisis (GFC) of 2008 and the migrant crisis in the European Union (starting in 2011 and continuing). The paper looks at these crises as narrative devices that intersect with memory politics in ways that heighten and intensify xenophobic and nationalist anxieties. The paper's discussion is primarily theoretical, complemented with evidence drawn from public statements and policy platforms of three key right-wing Eurosceptic parties in the United Kingdom, France, and Germany (the United Kingdom Independence Party (UKIP), the Rassemblement National (RN), and the Alternativ für Deutschland (AfD).

Volcanological observatories have common needs and often common practical issues for multi-disciplinary data monitoring applications. Real-time access to integrated data, technical metadata, modeling and estimation of uncertainties are fundamental for an efficient interpretation. But in fact, the heterogeneity of instruments or acquisition systems and the inherent problems to produce rapid models using real-time data lead to difficulties that may hinder crisis management. In an attempt to globally address these questions, the French volcanological and seismological observatories have developed a specific operational software system over the past 19 years. Based on GNU/Linux open source tools and a Web interface, the WebObs system mainly offers: (1) a modular database for equipment network management; (2) a dozen of evolving dedicated periodic tasks for each monitoring technique like seismology, deformations and geochemistry that use standard data formats with automated execution of periodic tasks that produce high-quality graphs on preset moving time intervals, data exports, optional event notifications including e-mail alerting, instruments status controls based on their data validity; (3) web-form interfaces for manual data input/editing and export; (4) a user request form to adjust the tasks parameters for a single execution and to produce customized graphs and data exports. This system hence constitutes a web-based tool that performs integrated, centralized and automated real-time volcano monitoring. It has therefore become a strong support for data analysis and exchange between researchers, engineers, and technicians during periods of unrest as well as periods of long-term quiescence. WebObs is also widely open for development of interdisciplinary modeling and enhanced data processing. This allows scientists to test new methods with real-time data flux and to instantaneously share their results in the community.