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A wide range of organisms use sex pheromones to communicate with each other and to identify appropriate mating partners. While the evolution of chemical communication has been suggested to cause sexual isolation and speciation, the mechanisms that govern evolutionary transitions in sex pheromone production are poorly understood. Here, we decipher the molecular mechanisms underlying the rapid evolution in the expression of a gene involved in sex pheromone production in Drosophilid flies. Long-chain cuticular hydrocarbons (e.g., dienes) are produced female-specifically, notably via the activity of the desaturase DESAT-F, and are potent pheromones for male courtship behavior in Drosophila melanogaster. We show that across the genus Drosophila, the expression of this enzyme is correlated with long-chain diene production and has undergone an extraordinary number of evolutionary transitions, including six independent gene inactivations, three losses of expression without gene loss, and two transitions in sex-specificity. Furthermore, we show that evolutionary transitions from monomorphism to dimorphism (and its reversion) in desatF expression involved the gain (and the inactivation) of a binding-site for the sex-determination transcription factor, DOUBLESEX. In addition, we documented a surprising example of the gain of particular cis-regulatory motifs of the desatF locus via a set of small deletions. Together, our results suggest that frequent changes in the expression of pheromone-producing enzymes underlie evolutionary transitions in chemical communication, and reflect changing regimes of sexual selection, which may have contributed to speciation among Drosophila.

The vinegar fly Drosophila melanogaster is a pivotal model for invertebrate development, genetics, physiology, neuroscience, and disease. The whole family Drosophilidae, which contains over 4,400 species, offers a plethora of cases for comparative and evolutionary studies. Despite a long history of phylogenetic inference, many relationships remain unresolved among the genera, subgenera, and species groups in the Drosophilidae. To clarify these relationships, we first developed a set of new genomic markers and assembled a multilocus data set of 17 genes from 704 species of Drosophilidae. We then inferred a species tree with highly supported groups for this family. Additionally, we were able to determine the phylogenetic position of some previously unplaced species. These results establish a new framework for investigating the evolution of traits in fruit flies, as well as valuable resources for systematics.

Abstract Dedifferentiated liposarcoma (DDLPS) is the most frequent high-grade soft tissue sarcoma subtype. It is characterized by a component of undifferentiated tumor cells coexisting with a component of well-differentiated adipocytic tumor cells. Both dedifferentiated (DD) and well-differentiated (WD) components exhibit MDM2 amplification, however their cellular origin remains elusive. Using single-cell RNA sequencing, DNA sequencing, in situ multiplex immunofluorescence and functional assays in paired WD and DD components from primary DDLPS tumors, we characterize the cellular heterogeneity of DDLPS tumor and micro-environment. We identify a population of tumor adipocyte stem cells (ASC) showing striking similarities with adipocyte stromal progenitors found in white adipose tissue. We show that tumor ASC harbor the ancestral genomic alterations of WD and DD components, suggesting that both derive from these progenitors following clonal evolution. Last, we show that DD tumor cells keep important biological properties of ASC including pluripotency and that their adipogenic properties are inhibited by a TGF-β-high immunosuppressive tumor micro-environment.

Abstract Psoriasis is a multifactorial, chronic inflammatory skin disease with unresolved questions on its primary events. Iron overload has been described in the epidermis of psoriasis patients, but its relevance remains unknown. We found that the key iron regulatory hormone hepcidin was highly expressed in the epidermis of psoriasis patients, especially the pustular variants resistant to treatments. In a murine model of acute skin inflammation, keratinocyte-derived hepcidin was required for iron retention in keratinocytes, leading to hyperproliferation of the epidermal layer and neutrophil recruitment, two main features of psoriatic skin lesions. Keratinocytes overexpressing hepcidin were sufficient to elicit these psoriasiform features in a transgenic mouse model. Furthermore, transcriptome analysis of these keratinocytes revealed canonical pathways found in human psoriasis, pointing to a causal role for hepcidin in the pathogenesis of the disease. Altogether, our data suggest that hepcidin could be an actionable target for skin psoriasis treatment, in addition to current therapeutics, or targeted as maintenance therapy during remission to prevent recurrence.

Abstract Transgender individuals experience elevated mental health issues and a diminished quality of life compared to the general population. While gender‐affirming dermatology treatments hold promise in addressing these challenges, there is a notable dearth of research in this area. Therefore, the objective of this study was to provide a comprehensive summary of the existing literature on the psychosocial effects of gender‐affirming dermatology treatments in transgender populations. A systematic review of original research on gender‐affirming dermatology treatments in transgender populations was conducted from PubMed (including Medline), Cochrane Library and Embase following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses 2020 guidelines. The search was limited to studies published after 1 January 2013 and was conducted on 26 June 2023. Relevant reviews were excluded but had their references screened. All studies that met the inclusion criteria also had their references screened. Article screening involved two steps: initial abstract/title screening using Rayyan.ia, followed by full‐text screening for selected articles. Risk of bias was assessed using Joanna Briggs Institute critical appraisal checklists. Thirteen studies were analyzed and most revealed a positive association between gender‐affirming dermatology treatments and favorable psychosocial outcomes. However, there was a large imbalance in the focus on transfeminine versus transmasculine individuals, alongside disparities in gender identification methods. Hair removal followed by nonsurgical injectables were the primary treatments studied. Most studies faced notable limitations, preventing a definitive causal relationship between gender‐affirming dermatology treatments and psychosocial effects. Across studies, there were discrepancies in the type of psychosocial outcome studied and a lack of standardized assessment tools. Despite these limitations, gender‐affirming dermatology treatments appear to have psychosocial benefits for transgender individuals, but further robust studies are needed for a comprehensive understanding of this relationship.

Abstract In MeLiM minipigs, melanomas develop around birth, can metastasize, and have histopathologic characteristics similar to humans. Interestingly, MeLiM melanomas eventually regress. This favorable outcome raises the question of their malignancy, which we investigated. We clinically followed tens of tumors from onset to first signs of regression. Transcriptome analysis revealed an enrichment of all cancer hallmarks in melanomas, although no activating or suppressing somatic mutation were found in common driver genes. Analysis of tumor cell genomes revealed high mutation rates without UV signature. Canonical proliferative, survival and angiogenic pathways were detected in MeLiM tumor cells all along progression stages. Functionally, we show that MeLiM melanoma cells are capable to grow in immunocompromised mice, with serial passages and for a longer time than in MeLiM pigs. Pigs set in place an immune response during progression with dense infiltration by myeloid cells while melanoma cells are deficient in B2M expression. To conclude, our data on MeLiM melanomas reveal several malignancy characteristics. The combination of these features with the successful spontaneous regression of these tumors make it an outstanding model to study an efficient anti-tumor immune response.

Microrganismos endofíticos são, em sua maioria, fungos ou bactérias que vivem no interior das plantas sem lhes causar prejuízos, estabelecendo uma associação mutualística íntima, tornando as plantas mais resistentes a ambientes com estresse, enquanto recebem nutrientes e proteção. Estudos indicam a grande capacidade destes organismos na produção de enzimas extracelulares hidrolíticas como amilases, lipases e celulases de metabólitos secundários que inibem o desenvolvimento de patógenos. O presente trabalho objetivou a bioprospecção de fungos endofíticos isolados da planta Azadirachtaindica, com o potencial de produção de enzimas hidrolíticas e controle do microrganismo Macrophomina phaseolina. Os fungos foram isolados previamente de A. indica, armazenados na micoteca do Laboratório de Entomologia Agrícola B09 da Universidade Católica Dom Bosco e identificados molecularmente. Para produção enzimática, os isolados foram inoculados em meios específicos para cada enzima: lipase, esterase, pectinase, amilase e protease. O teste de antagonismo foi conduzido em cultura pareada, avaliando os índices de antagonismo. Foi possível identificar os gêneros Colletotrichum, Diaporthe, Phyllosticta, Alternaria, Trichoderma, Phomopsis e Preussia, além de um identificado apenas ao nível da classe Sordariomycetes. Na produção enzimática, os isolados Preussia isomera (AI17B) e Alternaria sp. (AI30B) se destacaram, respectivamente, pela elevada produção de protease e pela diversidade de enzimas produzidas. Frente à M. phaseolina, apenas Alternaria sp. (AI30B) e Phyllosticta capitalensis (AI25B) demonstraram atividade antagonística. Com base nos resultados obtidos, a planta A. indica pode servir como hospedeira de fungos endofíticos com potencial biotecnológico e de biocontrole.

Abstract Background Dermal filler injections pose serious risks when administered by untrained individuals or when food and drug administration (FDA) guidelines are not adhered to. This issue may potentially be compounded by a growing reliance on social media platforms for health information. Objective Our objective was to analyze the quality of health information in videos published on dermal filler on TikTok. Methods We searched three hashtags, #filler (2.4 billion views), #dermalfiller (132.8 million views), and #fillersinjection (137.0 million views) and assessed the top videos returned by TikTok's algorithm that met inclusion criteria. The quality of health information was evaluated using the DISCERN instrument, a validated tool that uses a 1 to 5 scale to assess consumer health information. Results Videos received a mean DISCERN score of 1.64 (SD 0.33), indicating significantly low quality. 7% of the videos promoted non‐FDA‐approved uses of filler. Notably, videos posted by physician assistants or physicians received the highest mean scores (1.92 and 1.72) as well as videos categorized as educational (1.99). Conclusion Dermatologists should be aware of the high viewership of low‐quality TikTok videos on dermal filler. Dermatologists shall, therefore, understand the importance of their role in providing education to patients on this topic.

Background: The risk of SARS-CoV-2 transmission to health care workers in intensive care units (ICU) and the contribution of airborne and fomites to SARS-CoV-2 transmission remain unclear. To assess the rate of air and surface contamination and identify risk factors associated with this contamination in patients admitted to the ICU for acute respiratory failure due to SARS-CoV-2 pneumonia. Methods: Prospective multicentric non-interventional study conducted from June 2020 to November 2020 in 3 French ICUs. For each enrolled patient, 3 predefined surfaces were swabbed, 2 air samples at 1 m and 3 m from the patient’s mouth and face masks of 3 health care workers (HCW) were collected within the first 48 h of SARS-CoV-2 positive PCR in a respiratory sample. Droplet digital PCR and quantitative PCR were performed on different samples, respectively. Results: Among 150 included patients, 5 (3.6%, 95%CI: 1.2% to 8.2%) had positive ddPCR on air samples at 1 m or 3 m. Seventy-one patients (53.3%, CI95%: 44.5% to 62.0%) had at least one surface positive. Face masks worn by HCW were positive in 6 patients (4.4%, CI: 1.6% to 9.4%). The threshold of RT-qPCR of the respiratory sample performed at inclusion (odds ratio, OR= 0.88, 95%CI: 0.83 to 0.93, p

Abstract Resistance to endocrine treatments and CDK4/6 inhibitors is considered a near-inevitability in most patients with estrogen receptor positive breast cancers (ER + BC). By genomic and metabolomics analyses of patients’ tumours, metastasis-derived patient-derived xenografts (PDX) and isogenic cell lines we demonstrate that a fraction of metastatic ER + BC is highly reliant on oxidative phosphorylation (OXPHOS). Treatment by the OXPHOS inhibitor IACS-010759 strongly inhibits tumour growth in multiple endocrine and palbociclib resistant PDX. Mutations in the PIK3CA/AKT1 genes are significantly associated with response to IACS-010759. At the metabolic level, in vivo response to IACS-010759 is associated with decreased levels of metabolites of the glutathione, glycogen and pentose phosphate pathways in treated tumours. In vitro, endocrine and palbociclib resistant cells show increased OXPHOS dependency and increased ROS levels upon IACS-010759 treatment. Finally, in ER + BC patients, high expression of OXPHOS associated genes predict poor prognosis. In conclusion, these results identify OXPHOS as a promising target for treatment resistant ER + BC patients.

Abstract Despite recent advances in exfoliated vdW ferromagnets, the widespread application of 2D magnetism requires a Curie temperature (Tc) above room temperature as well as a stable and controllable magnetic anisotropy. Here we demonstrate a large-scale iron-based vdW material Fe4GeTe2 with the Tc reaching ~530 K. We confirmed the high-temperature ferromagnetism by multiple characterizations. Theoretical calculations suggested that the interface-induced right shift of the localized states for unpaired Fe d electrons is the reason for the enhanced Tc, which was confirmed by ultraviolet photoelectron spectroscopy. Moreover, by precisely tailoring Fe concentration we achieved arbitrary control of magnetic anisotropy between out-of-plane and in-plane without inducing any phase disorders. Our finding sheds light on the high potential of Fe4GeTe2 in spintronics, which may open opportunities for room-temperature application of all-vdW spintronic devices.

Homologous recombination deficiency is linked with platinum-based chemotherapy response in triple-negative breast cancer (TNBC) but methods to clinically identify these patients are lacking. Here, using patient-derived xenografts of TNBC the authors demonstrate that shallow HRD is predictive of response to platinum-based chemotherapy.

A new computational tool provides insights into the structure of the cerebellum in mammals.

Introduction In people with Parkinson’s (PwP) impaired mobility is associated with an increased falls risk. To improve mobility, dopaminergic medication is typically prescribed, but complex medication regimens result in suboptimal adherence. Exploring medication adherence and its impact on mobility in PwP will provide essential insights to optimise medication regimens and improve mobility. However, this is typically assessed in controlled environments, during one-off clinical assessments. Digital health technology (DHT) presents a means to overcome this, by continuously and remotely monitoring mobility and medication adherence. This study aims to use a novel DHT system (DHTS) (comprising of a smartphone, smartwatch and inertial measurement unit (IMU)) to assess self-reported medication adherence, and its impact on digital mobility outcomes (DMOs) in PwP.Methods and analysis This single-centre, UK-based study, will recruit 55 participants with Parkinson’s. Participants will complete a range of clinical, and physical assessments. Participants will interact with a DHTS over 7 days, to assess self-reported medication adherence, and monitor mobility and contextual factors in the real world. Participants will complete a motor complications diary (ON-OFF-Dyskinesia) throughout the monitoring period and, at the end, a questionnaire and series of open-text questions to evaluate DHTS usability. Feasibility of the DHTS and the motor complications diary will be assessed. Validated algorithms will quantify DMOs from IMU walking activity. Time series modelling and deep learning techniques will model and predict DMO response to medication and effects of contextual factors. This study will provide essential insights into medication adherence and its effect on real-world mobility in PwP, providing insights to optimise medication regimens.Ethics and dissemination Ethical approval was granted by London—142 Westminster Research Ethics Committee (REC: 21/PR/0469), protocol V.2.4. Results will be published in peer-reviewed journals. All participants will provide written, informed consent.Trial registration number ISRCTN13156149.

O presente artigo tem a finalidade de analisar o fenômeno dos populismos com interesse específico na cena latino-americana. Para isso, propõe-se uma atualização de termos e conceitos elaborados pela literatura e de um possível uso analítico para refletir acerca de situações concretas consideradas populistas nessa região. Desse modo, este trabalho analisa a nova ordem de populistas do século XXI em três países da América Latina: Venezuela, Brasil e México, visando verificar seus pontos de contato, semelhanças e diferenças. O estudo foi desenvolvido recorrendo à metodologia qualitativa e descritiva, contemplando revisão bibliográfica e análise empírica. A relevância do tema se justifica pela importância de entender o que vem acontecendo com as democracias em processo de estabilização, especialmente através de um olhar que parte do Sul Global. Como resultado, foi possível concluir que, nos últimos anos, a ascensão da onda populista vem contribuindo para a recessão democrática, de maneira que o populismo voltou a se apresentar – reformulado – na América Latina. O que se tem demonstrado é que os populismos, uma vez instalados no poder, têm um grande potencial para abalar de forma significativa as estruturas democráticas, dificultando a consolidação das democracias constitucionais na região.

ObjectivesAlthough paravertebral intramuscular fatty infiltration (known as myosteatosis) following a vertebral fracture is well-known, scarce data are available regarding interactions between muscle, bone, and other fat depots. Based on a homogeneous cohort comprising postmenopausal women with or without a history of fragility fracture, we aimed to better depict the interrelationship between myosteatosis and bone marrow adiposity (BMA).Methods102 postmenopausal women were included, 56 of whom had a fragility fracture. Mean proton density fat fraction (PDFF) was measured in the psoas (PDFFPsoas) and paravertebral (PDFFParavertebral) muscles at the lumbar level, as well as in the lumbar spine and non-dominant hip using chemical shift encoding-based water-fat imaging. Visceral adipose tissue (VAT) and total body fat (TBF) were assessed using dual X-ray absorptiometry. Statistical models were adjusted for age, weight, height (all comparisons), and bone mineral density (when considering BMA).ResultsPDFF in the psoas and paravertebral muscles was higher in the fracture group compared to controls even after adjustment for age, weight, and height (PDFFPsoas = 17.1 ± 6.1% versus 13.5 ± 4.9%, p=0.004; PDFFParavertebral = 34.4 ± 13.6% versus 24.9 ± 8.8%, p=0.002). Higher PDFFParavertebral was associated with lower PDFF at the lumbar spine (β = -6.80 ± 2.85, p=0.022) among controls but not in the fracture group. In both groups, a significant relationship between higher PDFFPsoas and higher VAT was observed (β = 20.27 ± 9.62, p=0.040 in the fracture group, and β = 37.49 ± 8.65, p

During the 2020 pandemic, the sudden emergence of distance learning for children, combined with teleworking for parents, affected family organisation arrangements. Using data from a questionnaire filled in by 1.280 parents of primary school pupils in two Swiss cantons and a focus group interview conducted with six mothers, we explore how the supervision of children’s schoolwork was organised within parental couples and how it has been articulated with the parents’ professional activity and housework. Far from serving as a trigger for shared responsibility in couples, this period revealed and reinforced long-standing gender inequalities in the division of parental and domestic tasks.

Dual photo- and metal-catalysis is generally not well-understood when the metal catalyst is a gold complex. Here the authors show that a variation of a known metallaphotoredox annulation is possible without an added photocatalyst, proceeding putatively through a gold–intermediate photosensitization by the aggregate of a potassium amide reactant, and yielding indole derivatives.

IntroductionParkinson's disease (PD) is a neurodegenerative disorder which requires complex medication regimens to mitigate motor symptoms. The use of digital health technology systems (DHTSs) to collect mobility and medication data provides an opportunity to objectively quantify the effect of medication on motor performance during day-to-day activities. This insight could inform clinical decision-making, personalise care, and aid self-management. This study investigates the feasibility and usability of a multi-component DHTS to remotely assess self-reported medication adherence and monitor mobility in people with Parkinson's (PwP).MethodsThirty participants with PD [Hoehn and Yahr stage I (n = 1) and II (n = 29)] were recruited for this cross-sectional study. Participants were required to wear, and where appropriate, interact with a DHTS (smartwatch, inertial measurement unit, and smartphone) for seven consecutive days to assess medication adherence and monitor digital mobility outcomes and contextual factors. Participants reported their daily motor complications [motor fluctuations and dyskinesias (i.e., involuntary movements)] in a diary. Following the monitoring period, participants completed a questionnaire to gauge the usability of the DHTS. Feasibility was assessed through the percentage of data collected, and usability through analysis of qualitative questionnaire feedback.ResultsAdherence to each device exceeded 70% and ranged from 73 to 97%. Overall, the DHTS was well tolerated with 17/30 participants giving a score > 75% [average score for these participants = 89%, from 0 (worst) to 100 (best)] for its usability. Usability of the DHTS was significantly associated with age (ρ = −0.560, BCa 95% CI [−0.791, −0.207]). This study identified means to improve usability of the DHTS by addressing technical and design issues of the smartwatch. Feasibility, usability and acceptability were identified as key themes from PwP qualitative feedback on the DHTS.ConclusionThis study highlighted the feasibility and usability of our integrated DHTS to remotely assess medication adherence and monitor mobility in people with mild-to-moderate Parkinson's disease. Further work is necessary to determine whether this DHTS can be implemented for clinical decision-making to optimise management of PwP.

Uveal Melanoma (UM) is a rare and malignant intraocular tumor with dismal prognosis. Even if radiation or surgery permit an efficient control of the primary tumor, up to 50% of patients subsequently develop metastases, mainly in the liver. The treatment of UM metastases is challenging and the patient survival is very poor. The most recurrent event in UM is the activation of Gαq signaling induced by mutations in GNAQ/11. These mutations activate downstream effectors including protein kinase C (PKC) and mitogen-activated protein kinases (MAPK). Clinical trials with inhibitors of these targets have not demonstrated a survival benefit for patients with UM metastasis. Recently, it has been shown that GNAQ promotes YAP activation through the focal adhesion kinase (FAK). Pharmacological inhibition of MEK and FAK showed remarkable synergistic growth-inhibitory effects in UM both in vitro and in vivo. In this study, we have evaluated the synergy of the FAK inhibitor with a series of inhibitors targeting recognized UM deregulated pathways in a panel of cell lines. The combined inhibition of FAK and MEK or PKC had highly synergistic effects by reducing cell viability and inducing apoptosis. Furthermore, we demonstrated that these combinations exert a remarkable in vivo activity in UM patient-derived xenografts. Our study confirms the previously described synergy of the dual inhibition of FAK and MEK and identifies a novel combination of drugs (FAK and PKC inhibitors) as a promising strategy for therapeutic intervention in metastatic UM.

Despite growing evidence of links between sulcation and function in the adult brain, the folding dynamics, occurring mostly before normal-term-birth, is vastly unknown. Looking into the development of cortical sulci in infants can give us keys to address fundamental questions: what is the sulcal shape variability in the developing brain? When are the shape features encoded? How are these morphological parameters related to further functional development?In this study, we aimed to investigate the shape variability of the developing central sulcus, which is the frontier between the primary somatosensory and motor cortices. We studied a cohort of 71 extremely preterm infants scanned twice using MRI – once around 30 weeks post-menstrual age (w PMA) and once at term-equivalent age, around 40w PMA –, in order to quantify the sulcus's shape variability using manifold learning, regardless of age-group or hemisphere. We then used these shape descriptors to evaluate the sulcus's variability at both ages and to assess hemispheric and age-group specificities. This led us to propose a description of ten shape features capturing the variability in the central sulcus of preterm infants. Our results suggested that most of these features (8/10) are encoded as early as 30w PMA. We unprecedentedly observed hemispheric asymmetries at both ages, and the one captured at term-equivalent age seems to correspond with the asymmetry pattern previously reported in adults. We further trained classifiers in order to explore the predictive value of these shape features on manual performance at 5 years of age (handedness and fine motor outcome). The central sulcus's shape alone showed a limited but relevant predictive capacity in both cases. The study of sulcal shape features during early neurodevelopment may participate to a better comprehension of the complex links between morphological and functional organization of the developing brain.

Abstract Evolution is a key concept of biology, fundamental to understand the world and address important societal problems, but research studies show that it is still not widely understood and accepted. Several factors are known to influence evolution acceptance and understanding, but little information is available regarding the impacts of the curriculum on these aspects. Very few curricula have been examined to assess the coverage of biological evolution. The available studies do not allow comparative analyses, due to the different methodologies employed by the authors. However, such an analysis would be useful for research purposes and for the development of appropriate educational policies to address the problem of a lack of evolution acceptance in some countries. In this paper we describe the steps through which we developed a valid and reliable instrument for curricula analysis known as FACE: “Framework to Assess the Coverage of biological Evolution by school curricula.” This framework was developed based on the “Understanding Evolution Conceptual Framework” (UECF). After an initial pilot study, our framework was reformulated based on identified issues and experts’ opinions. To generate validity and reliability evidence in support of the framework, it was applied to four European countries’ curricula. For each country, a team of a minimum of two national and two foreign coders worked independently to assess the curriculum using this framework for content analysis. Reliability evidence was estimated using Krippendorf's alpha and resulted in appropriate values for coding the examined curricula. Some issues that coders faced during the analysis were discussed and, to ensure better reliability for future researchers, additional guidelines and one extra category were included in the framework. The final version of the framework includes six categories and 34 subcategories. FACE is a useful tool for the analysis and the comparison of curricula and school textbooks regarding the coverage of evolution, and such results can guide curricula development.

Objective: Hypoparathyroidism is a known complication of total laryngectomy, although parathyroid preservation and/or reimplantation are not routine. Autofluorescence is a new technique for identifying parathyroid glands intraoperatively. The aim of this study was to evaluate the feasibility of autofluorescence in this context. Materials and Methods: A retrospective study of patients undergoing total laryngectomy/pharyngectomy with concomitant thyroidectomy using the Fluobeam® (Fluoptics, Grenoble, France) and frozen section of a parathyroid fragment in case of reimplantation. The rates of identification using autofluorescence, reimplantation, and hypoparathyroidism were evaluated. Results: Eighteen patients (16 males, median age 67) underwent total laryngectomy/pharyngectomy with total thyroidectomy (n = 12) or hemithyroidectomy (n = 6). A median of 2 parathyroid glands were identified per patient. Ninety-two percent were identified by autofluorescence before visualisation. All parathyroids were reimplanted due to devascularization. Temporary hypoparathyroidism occurred in nine patients, and was permanent in one patient. After 34 months of median follow-up (range 1–49), no tumor recurrence was observed in the reimplantation sites. Conclusions: To our knowledge, this is the largest study to evaluate autofluorescence during total laryngectomy with thyroidectomy. No tumor recurrence occurred in the sites of parathyroid reimplantation.

Aim: Exposure to repeated gait perturbations improves the balance of older adults (OAs) and decreases their risks of falling, but little is known about the underpinning mechanical adjustments. We aimed to quantify the changing temporo-spatial and kinetic characteristics of balance recovery following repeated backward slips to better understand the mechanical adjustments responsible for improved balance.Methods: We exposed 17 young adults (YAs) (25.2 ± 3.7 years) and 17 OAs (62.4 ± 6.6 years) to 10 backward slips simulated on an instrumented treadmill by unilateral backward belt accelerations. We measured the balance of the participants (margin of stability: MoS), balance recovery (nsteps: number of steps necessary to return to a steady gait for at least three consecutive steps), temporo-spatial (step length), and kinetics [ground reaction force (GRF) angle, lower limb joint moments] for 15 steps following each slip. The results were compared with baseline.Results: Participants in both groups improved their MoS and nsteps with repeated exposure to the slips, but no significant effect of age was detected. During the perturbed step, the GRF vector was directed more posteriorly during mid-stance and more anteriorly during push-off than baseline, which resulted in a longer step. These adjustments were maintained from the first (Slip01) to the last (Slip10) slip, and by Slip10 were correlated with better balance (MoS) on the second recovery step. During the first recovery step following Slip01, participants developed lower plantarflexor and larger knee extensor moments whilst taking a shorter step, these adjustments were correlated with poorer balance and were not maintained with repeated slips. Joint moments and step length of the first recovery step returned to normal levels by Slip10.Conclusion: Young adults and OAs improved their balance with repeated slips. The adjustments that were positively correlated with balance (changes in step length, GRF angle) were maintained whilst those that were not (changes in joint moments) were discarded. All the responses observed in Slip10 were observed in Slip01. The observed balance improvements were achieved by refining the initial strategy rather than by developing a new one. The underlying mechanics were correlated with step length of the first recovery steps, which was associated with balance and should be monitored in fall prevention interventions.

Ischemia and reperfusion injury is an early inflammatory process during liver transplantation that impacts on graft function and clinical outcomes. Interleukin (IL)-33 is a danger-associated molecular pattern involved in kidney ischemia/reperfusion injury and several liver diseases. The aims were to assess whether IL-33 was released as an alarmin responsible for ischemia/reperfusion injury in a mouse model of warm hepatic ischemia, and whether this hypothesis could also apply in the setting of human liver transplantation. First, a model of warm hepatic ischemia/reperfusion was used in wild-type and IL-33–deficient mice. Severity of ischemia/reperfusion injury was assessed with ALT and histological analysis. Then, serum IL-33 was measured in a pilot cohort of 40 liver transplant patients. Hemodynamic postreperfusion syndrome, graft dysfunction (assessed by model for early allograft scoring >6), renal failure, and tissue lesions on time-zero biopsies were assessed. In the mouse model, IL-33 was constitutively expressed in the nucleus of endothelial cells, immediately released in response to hepatic pedicle clamping without neosynthesis, and participated in the recruitment of neutrophils and tissue injury on site. The kinetics of IL-33 in liver transplant patients strikingly matched the ones in the animal model, as attested by serum levels reaching a peak immediately after reperfusion, which correlated to clinical outcomes including postreperfusion syndrome, posttransplant renal failure, graft dysfunction, and histological lesions of ischemia/reperfusion injury. IL-33 was an independent factor of graft dysfunction with a cutoff of IL-33 at 73 pg/ml after reperfusion (73% sensitivity, area under the curve of 0.76). Taken together, these findings establish the immediate implication of IL-33 acting as an alarmin in liver I/R injury and provide evidence of its close association with cardinal features of early liver injury-associated disorders in LT patients.

In the Eastern Amazon is the largest continuous coconut crop area in the world. This region is known for its high precipitation levels and an ecosystem of extensive insect biodiversity. It is important to know the local entomofauna and to know whether there is a balance between the different insect groups. This study aimed to understand the influence of seasonality on the dynamics of edaphic insect families, comparing the environment as a whole and in different commercial coconut crop areas and riparian forests in the Eastern Amazon. Forty pitfall traps were installed in the ground at an average distance of 1 m from the coconut stipe. They were filled with 200 ml of an aqueous solution of liquid neutral soap and 70% alcohol. Traps were installed in eight areas: an area of riparian forest (A1) and seven in commercial coconut crop areas (A2 to A8), in the Amazon dry and rainy season. The similarity between the insects was measured using Euclidean distance. The abundance of families in each collection area used qualitative similarity. For family dominance, quantitative similarity was used. Diversity analyses were performed to justify the similarities of the clusters through the Shannon and Simpson Indices. In total, 252,313 individuals, 118 families, and 9 orders were collected. There were many Formicidae in both climatic periods because it is a social insect and has edaphic habits. The families with the most individuals in the collections were Drosophilidae, Staphylinidae, Bostrichidae, Phoridae, Nitidulidae, Scolytidae, Tenebrionidae, Scarabaeidae, Ceratopogomidae, and Platyogastridae. The riparian forest area (A1) showed the greatest diversity and least dominance. The oldest cultivated areas A2 and A3 (7 years) showed the greatest diversity in the dry season. In the rainy season, the most diversified areas were those with the highest land slope (A6 and A7). The most dominant areas were A5 and A8, where the largest number of Solenopsis spp. were found. This study showed the importance of obtaining basic information about coconut entomofauna and conducting research on insect dynamics in agricultural crops in the Amazon region.

Participants exposed to a simulated slip with forward loss of balance (FLB) develop large lower limb joint moments which may be a limiting factor for those whose muscle-tendon units’ (MTUs) properties are deteriorated. Whether the age-related decline in these properties limits participants’ capacity to recover their balance following a slip with FLB remains unclear. We combined isokinetic dynamometry, ultrasound and EMG to understand how knee extensor and ankle plantarflexor muscle strength and power, rate of moment development, electromechanical delay, and tendon stiffness affected the balance of young (25.3 ± 3.9 years) and older adults (62.8 ± 7.1 years) when recovering from a single slip with FLB triggered whilst walking on a split-belt instrumented treadmill. Except for the patellar tendon’s stiffness, knee extensor and ankle plantarflexor electromechanical delays, older adults’ MTUs properties were deteriorated compared to those of young participants (p < 0.05). We found no significant relationship between age or the MTUs properties of participants and balance recovery. These findings provide additional support that neither maximal nor explosive strength training are likely to be successful in preventing a fall for healthy older adults, and that other type of interventions, such as task-specific training that has already proved efficacious in reducing the risk of falling, should be developed.

Aim: Falls commonly occur from trips and slips while walking. Recovery strategies from trips and backward falling slips have been extensively studied. However, until recently, forward falling slips (FFSs) have been considered less dangerous and have been understudied. This study aimed first to create an application to realistically simulate FFSs using a split-belt instrumented treadmill and then to understand the biomechanical requirements for young adults to recover from an FFS.Methods: We developed a semi-automatic custom-made application on D-Flow that triggered FFSs by briefly and unexpectedly increasing the speed (a = 5 m·s−2) of the right belt during stance. To validate the protocol, we tested against criteria defined for an ecologically and experimentally valid FFS: unexpected occurrence of the slip, increased foot velocity, forward loss of balance during the slip and consistent perturbation timing. We evaluated the recovery strategies of 17 young adults by measuring dynamic stability, joint moments and ground reaction force (GRF) vector angles before, during and on 15 steps following the FFS.Results: The application successfully triggered FFSs, according to the criteria we defined. Participants' balance returned to normal for a minimum of three consecutive steps in 10.9 (7.0) steps. Recovery from the FFSs was characterised by larger hip flexor and knee extensor moments to support the centre of mass during the slip, and a longer first recovery step with large hip extensor moments to arrest the fall followed by large knee extensor moments to raise and advance the centre of mass into the next step (p < 0.001 compared with normal gait). Subsequent steps progressively returned to normal.Conclusion: This is the first study to experimentally simulate FFSs meeting the aforementioned criteria, and to measure their effects on the dynamic balance and kinetic parameters. The split-belt instrumented treadmill proved a promising tool to better study the mechanisms of falls and recovery. The required large hip and knee joint moments generally agree with findings on trips and backward falling slips and provide an indication of the functional capacities that should be targeted in fall-prevention interventions. These findings should be used to better understand and target the mechanisms of balance loss and falls in older adults following FFSs.

Experiments in cadavers have demonstrated significant mechanical interactions between constituents of myofascial chains. However, evidence for such force transmission effects is scarce under in vivo conditions. The purpose of this trial was to examine the impact of ankle motion on soft tissue displacement of the dorsal thigh. Eleven healthy active individuals (26.8 ± 4.3 years, six males), in prone position and with the knee extended, underwent passive calf stretches (ankle dorsal extension) imposed by an isokinetic dynamometer. High-resolution ultrasound was used to simultaneously capture the displacement of the semimembranosus muscle, which was quantified by means of cross-correlation analysis. Inactivity of the leg muscles was controlled using surface electromyography (EMG). One participant had to be excluded due to major EMG activity during the experiment. According to a one-sample t test testing the difference to the neutral zero position, ankle dorsal extension induced substantial caudal muscle displacements (5.76 ± 2.67 mm, p < 0.0001). Correlation analysis (Spearman), furthermore, revealed a strong association between maximal dorsal extension and semimembranosus motion (rho = 0.76, p = 0.02). In conclusion, the present trial provides initial in vivo evidence for a mechanical force transmission between serially connected skeletal muscles. This means that local alterations of the mechanical tissue properties may modify flexibility in neighboring (superior or inferior) joints.

Treatments currently used to prevent congenital toxoplasmosis are non-specific of Toxoplasma gondii and have grievous side effects. To develop a more specific and less toxic drug, we have designed SP230, an imidazo[1,2-b]pyridazine salt targeting the Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) and active against acute toxoplasmosis in mice. Efficiency of SP230 to inhibit foetal transmission of the parasite was evaluated in a mouse model of congenital toxoplasmosis. Swiss mice were infected at mid-pregnancy with tachyzoites or cysts of the ME49 strain of T. gondii by intraperitoneal and oral route, respectively, and treated with SP230 at 50 mg/kg for 5 days by the same routes. Parasite burden in organs of dams and in foetuses was measured by quantitative PCR. Intraperitoneal administration of SP230 drastically reduced the number of parasites (more than 97% of reduction) in the brain and lungs of dams, and led to a reduction of 66% of parasite burden in foetuses. Oral administration of SP230 was particularly efficient with 97% of reduction of parasite burdens in foetuses. SP230 did not impact number and weight of offspring in our conditions. This inhibitor of TgCDPK1 is a promising candidate for the development of alternative therapeutics to treat infected pregnant women.

Body plans, which characterize the anatomical organization of animal groups of high taxonomic rank, often evolve by the reduction or loss of appendages (limbs in vertebrates and legs and wings in insects, for example). In contrast, the addition of new features is extremely rare and is thought to be heavily constrained, although the nature of the constraints remains elusive. Here we show that the treehopper (Membracidae) 'helmet' is actually an appendage, a wing serial homologue on the first thoracic segment. This innovation in the insect body plan is an unprecedented situation in 250 Myr of insect evolution. We provide evidence suggesting that the helmet arose by escaping the ancestral repression of wing formation imparted by a member of the Hox gene family, which sculpts the number and pattern of appendages along the body axis. Moreover, we propose that the exceptional morphological diversification of the helmet was possible because, in contrast to the wings, it escaped the stringent functional requirements imposed by flight. This example illustrates how complex morphological structures can arise by the expression of ancestral developmental potentials and fuel the morphological diversification of an evolutionary lineage. [ABSTRACT FROM AUTHOR]