Search

Background/Objectives: Neurodegenerative ocular diseases, such as age-related macular degeneration (AMD) and glaucoma, represent growing public health concerns. Oxidative stress plays a key role in their development, damaging retinal cells and accelerating disease progression. Melatonin (Mel) is a potent antioxidant with neuroprotective properties; however, it faces limitations such as low solubility. This study proposes the use of human serum albumin nanoparticles (Np-HSA) to enhance the delivery of Mel to the posterior segment of the eye and evaluates its neuroprotective and anti-apoptotic effects on the retina. Methods: A model of retinal degeneration was induced in New Zealand albino rabbits using cytotoxic and oxidative agents. Np-HSA-Mel nanoparticles were administered subconjunctivally, and cellular viability and retinal functionality were assessed using flow cytometry and pupillary light reflex (PLR). Histological and immunohistochemical studies, including the TUNEL assay, were performed to analyse cell survival and apoptotic index. Results: Np-HSA-Mel significantly preserved pupillary function and cell viability, demonstrating lower apoptosis compared to Mel solution and Np-HSA alone. Histologically, eyes treated with Np-HSA-Mel exhibited fewer structural alterations and greater cellular organisation. The TUNEL assay confirmed a significant reduction in the apoptotic index of retinal ganglion cells (RGCs) treated with Np-HSA-Mel. Conclusions: Np-HSA-Mel effectively overcame ocular barriers, achieving greater neuroprotective efficacy at the retinal level. These findings highlight the synergistic potential of albumin and Mel in treating neurodegenerative ocular diseases, opening new perspectives for future therapies.

Living Donor Liver Transplantation (LDLT) is a promising approach to treating end-stage liver diseases, however, some post-operatory complications such as pneumonia, bacteremia, urinary tract infections, and hepatic dysfunction have been reported. In murine models using partial hepatectomy (PHx), a model that emulates LDLT, it has been determined that the synthesis of hepatic cell proliferation factors that are associated with noradrenaline synthesis are produced in locus coeruleus (LC). In addition, studies have shown that PHx decreases GABA and 5-HT2A receptors, promotes loss of dendritic spines, and favors microgliosis in rat hippocampus. The GABA and serotonin-altered circuits suggest that catecholaminergic neurons such as dopamine and noradrenaline neurons, which are highly susceptible to cellular stress, can also be damaged. To understand post-transplant affections and to perform well-controlled studies it is necessary to know the potential causes that explain as a liver surgical procedure can produce brain damage. In this paper, we review several cellular processes that could induce gliosis in LC after rat PHx.

En los últimos años se han establecido centros de simulación médica especializados con el propósito de cultivar las habilidades esenciales para los médicos. Estos centros proporcionan entornos seguros de aprendizaje, empleando distintas herramientas para la realización de prácticas deliberadas y escenarios clínicos. Con el auge tecnológico, la realidad virtual y aumentada se ha desarrollado en distintos ámbitos, incluyendo el área de la salud. Diversos estudios han confirmado que las metodologías de aprendizaje activas generan un impacto positivo, facilitando una comprensión más profunda del contenido, un aumento en el aprendizaje y una retención a largo plazo. Además, fomentan la colaboración y la motivación en los estudiantes. En todo el mundo, y específicamente en México, el paro cardiorrespiratorio figura como una de las principales causas de muerte. Este estudio se enfoca en explorar la aplicabilidad de la realidad virtual en la reanimación cardiopulmonar como una herramienta de enseñanza en simulaciones clínicas. Dada la capacidad de esta intervención para salvar vidas, es crucial que los estudiantes de medicina adquieran y dominen estas habilidades vitales.

IntroductionClimate change has increased the need for forest restoration, but low planting success and limited availability of planting materials hamper these efforts. Invasive plants and their soil legacies can further reduce restoration success. Thus, strategies that optimize restoration are crucial. Assisted migration and inoculation with native microbial symbiont communities have great potential to increase restoration success. However, assisted migrants can still show reduced survival compared to local provenances depending on transfer distance. Inoculation with mycorrhizal fungi, effective if well-matched to plants and site conditions, can have neutral to negative results with poor pairings. Few studies have examined the interaction between these two strategies in realistic field environments where native plants experience the combined effects of soil legacies left by invasive plants and the drought conditions that result from a warming, drying climate.MethodsWe planted two ecotypes (local climate and warmer climate) of Populus fremontii (Fremont cottonwoods), in soils with and without legacies of invasion by Tamarix spp. (tamarisk), and with and without addition of native mycorrhizal fungi and other soil biota from the warmer climate.ResultsFour main results emerged. 1) First year survival in soil legacies left behind after tamarisk invasion and removal was less than one tenth of survival in soil without a tamarisk legacy. 2) Actively restoring soil communities after tamarisk removal tripled first year cottonwood survival for both ecotypes, but only improved survival of the warmer, assisted migrant ecotype trees in year two. 3) Actively restoring soil communities in areas without a tamarisk history reduced first year survival for both ecotypes, but improved survival of the warmer, assisted migrant ecotype trees in year two. 4) By the second year, inoculated assisted migrants survived at five times the rate of inoculated trees from the local ecotype.DiscussionResults emphasize the detrimental effects of soil legacies left after tamarisk invasion and removal, the efficacy of assisted migration and restoring soil communities alongside plants, and the need to thoughtfully optimize pairings between plants, fungi, and site conditions.

Abstract Background Several cytotoxic chemotherapies have demonstrated efficacy in improving recurrence‐free survival (RFS) following resection of Stage II–IV colorectal cancer (CRC). However, the temporal dynamics of response to such adjuvant therapy have not been systematically quantified. Methods The Cochrane Central Register of Trials, Medline (PubMed) and Web of Science were queried from database inception to February 23, 2023 for Phase III randomized controlled trials (RCTs) where there was a significant difference in RFS between adjuvant chemotherapy and surgery only arms. Summary data were extracted from published Kaplan–Meier curves using DigitizeIT. Absolute differences in RFS event rates were compared at matched intervals using multiple paired t‐tests. Results The initial search yielded 1469 manuscripts. After screening, 18 RCTs were eligible (14 Stage II/III; 4 Stage IV), inclusive of 16,682 patients. In the absence of adjuvant chemotherapy, the greatest rate of recurrence was observed in the first year (mean RFS event rate; 0–0.5 years: 0.22 ± 0.21; 0.5–1 years: 0.20 ± 0.09). Adjuvant chemotherapy was associated with significant decreases in the RFS event rates for the intervals 0–0.5 years (0.09 ± 0.09 vs. 0.22 ± 0.21, p

El trabajo se plantea analizar la participación argentina en las misiones de paz dirigidas por Naciones Unidas, posteriores al retorno de la democracia en 1983 hasta el presente. El mismo propone recorrer las diversas presidencias y presentar cómo la participación en las misiones de paz se mantiene en forma ininterrumpida a pesar de los diversos contextos internos de los últimos años. ¿Las misiones de paz son un pilar básico de la Política Exterior Argentina?

Phaseolotoxin is a major virulence factor of the bean pathogen bacterium P. savastanoi pv. phaseolicola. This toxin plays a key role in the development of the halo blight disease in bean plants. So far, the signal transduction pathways involved in the synthesis of phaseolotoxin have not been elucidated. The influence of regulation mechanisms related to the oxidative stress response, in particular the OxyR protein, it has been suggested to be involved in this process.. In this study we evaluated the role of OxyR in P. savastanoi pv. phaseolicola, mainly compared to the synthesis of phaseolotoxin and the virulence of this phytopathogen. Generation of the oxyR-mutant, pathogenicity and virulence tests, and analyses of gene expression by RT-PCR assays were performed. The results showed that OxyR exerts an effect on the synthesis of phaseolotoxin and positively influences the expression of the Pht and Pbo cluster genes. Likewise, OxyR influences the production of pyoverdine by the control of the expression of the genes encoding the PvdS sigma factor, involved in the synthesis of this pigment. This study is the first report on members of the OxyR regulon of P. savastanoi pv. phaseolicola NPS3121.

Sleep disturbances after ischaemic stroke include alterations of sleep architecture, obstructive sleep apnea, restless legs syndrome, daytime sleepiness and insomnia. Our aim was to explore their impacts on functional outcomes at month 3 after stroke, and to assess the benefit of continuous positive airway pressure in patients with severe obstructive sleep apnea. Ninety patients with supra-tentorial ischaemic stroke underwent clinical screening for sleep disorders and polysomnography at day 15 ± 4 after stroke in a multisite study. Patients with severe obstructive apnea (apnea-hypopnea index ≥ 30 per hr) were randomized into two groups: continuous positive airway pressure-treated and sham (1:1 ratio). Functional independence was assessed with the Barthel Index at month 3 after stroke in function of apnea-hypopnea index severity and treatment group. Secondary objectives were disability (modified Rankin score) and National Institute of Health Stroke Scale according to apnea-hypopnea index. Sixty-one patients (71.8 years, 42.6% men) completed the study: 51 (83.6%) had obstructive apnea (21.3% severe apnea), 10 (16.7%) daytime sleepiness, 13 (24.1%) insomnia, 3 (5.7%) depression, and 20 (34.5%) restless legs syndrome. Barthel Index, modified Rankin score and Stroke Scale were similar at baseline and 3 months post-stroke in the different obstructive sleep apnea groups. Changes at 3 months in those three scores were similar in continuous positive airway pressure versus sham-continuous positive airway pressure patients. In patients with worse clinical outcomes at month 3, mean nocturnal oxygen saturation was lower whereas there was no association with apnea-hypopnea index. Poorer outcomes at 3 months were also associated with insomnia, restless legs syndrome, depressive symptoms, and decreased total sleep time and rapid eye movement sleep., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Synucleinopathies-related disorders such as Lewy body dementia (LBD) and isolated/idiopathic REM sleep behavior disorder (iRBD) have been associated with neuroinflammation. In this study, we examined whether the human leukocyte antigen (HLA) locus plays a role in iRBD and LBD. In iRBD, HLA-DRB1*11:01 was the only allele passing FDR correction (OR = 1.57, 95% CI = 1.27-1.93, p = 2.70e-05). We also discovered associations between iRBD and HLA-DRB1 70D (OR = 1.26, 95%CI = 1.12-1.41, p = 8.76e-05), 70Q (OR = 0.81, 95%CI = 0.72-0.91, p = 3.65e-04) and 71R (OR = 1.21, 95%CI = 1.08-1.35, p = 1.35e-03). Position 71 (p omnibus  = 0.00102) and 70 (p omnibus  = 0.00125) were associated with iRBD. Our results suggest that the HLA locus may have different roles across synucleinopathies., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Genomic stability in normal cells is crucial to avoid oncogenesis. Accordingly, multiple components of the DNA damage response (DDR) operate as bona fide tumor suppressor proteins by preserving genomic stability, eliciting the demise of cells with unrepairable DNA lesions, and engaging cell-extrinsic oncosuppression via immunosurveillance. That said, DDR sig-naling can also favor tumor progression and resistance to therapy. Indeed, DDR signaling in cancer cells has been consistently linked to the inhibition of tumor-targeting immune responses. Here, we discuss the complex interactions between the DDR and inflammation in the context of oncogenesis, tumor progression, and response to therapy., Significance: Accumulating preclinical and clinical evidence indicates that DDR is intimately connected to the emission of immunomodulatory signals by normal and malignant cells, as part of a cell-extrinsic program to preserve organismal homeostasis. DDR-driven inflammation, however, can have diametrically opposed effects on tumor-targeting immunity. Understanding the links between the DDR and inflammation in normal and malignant cells may unlock novel immunotherapeutic paradigms to treat cancer., (©2023 American Association for Cancer Research.)

NPC1 encodes a lysosomal protein involved in cholesterol transport. Biallelic mutations in this gene may lead to Niemann-Pick disease type C (NPC), a lysosomal storage disorder. The role of NPC1 in alpha synucleinopathies is still unclear, as different genetic, clinical, and pathological studies have reported contradictory results. This study aimed to evaluate the association of NPC1 variants with the synucleinopathies Parkinson's disease (PD), dementia with Lewy bodies (DLB), and rapid eye movement-sleep behavior disorder (RBD). We analyzed common and rare variants from 3 cohorts of European descent: 1084 RBD cases and 2945 controls, 2852 PD cases and 1686 controls, and 2610 DLB cases and 1920 controls. Logistic regression models were used to assess common variants while optimal sequence Kernel association tests were used to assess rare variants, both adjusted for sex, age, and principal components. No variants were associated with any of the synucleinopathies, supporting that common and rare NPC1 variants do not play an important role in alpha synucleinopathies., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: We recently demonstrated in a randomized controlled trial (APOMORPHEE, NCT02940912) that night-time only subcutaneous apomorphine infusion improves sleep disturbances and insomnia in patients with advanced Parkinson's disease and moderate to severe insomnia., Objectives: To identify the best candidates for receiving night-time only subcutaneous apomorphine infusion in routine care., Methods: In this post-hoc analysis of APOMORPHEE, we compared the characteristics of patients according to whether they chose to continue night-time only subcutaneous apomorphine infusion at the end of the study period or not., Results: Half of the patients (22/42) chose to continue the treatment. Off duration (day or night), painful Off dystonia, and insomnia severity at baseline were associated with night-time only apomorphine continuation. Multivariate analysis retained only Off duration as an independent predictor of continuation., Conclusions: The best candidates for night-time only apomorphine are patients with severe and prolonged Off periods (day or night) and severe insomnia., (© 2023 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Up to 30% of breast cancer (BC) patients treated with neoadjuvant chemotherapy (NCT) will relapse. Our objective was to analyze the predictive capacity of several markers associated with immune response and cell proliferation combined with clinical parameters., Methods: This was a single-center, retrospective cohort study of BC patients treated with NCT (2001-2010), in whom pretreatment biomarkers were analyzed: neutrophil-to-lymphocyte ratio (NLR) in peripheral blood, CD3+ tumor-infiltrating lymphocytes (TILs), and gene expression of AURKA, MYBL2 and MKI67 using qRT-PCR., Results: A total of 121 patients were included. Median followup was 12 years. In a univariate analysis, NLR, TILs, AURKA, and MYBL2 showed prognostic value for overall survival. In multivariate analyses, including hormone receptor, HER2 status, and response to NCT, NLR (HR 1.23, 95% CI 1.01-1.75), TILs (HR 0.84, 95% CI 0.73-0.93), AURKA (HR 1.05, 95% CI 1.00-1.11) and MYBL2 (HR 1.19, 95% CI 1.05-1.35) remained as independent predictor variables., Conclusion: Consecutive addition of these biomarkers to a regression model progressively increased its discriminatory capacity for survival. Should independent cohort studies validate these findings, management of early BC patients may well be changed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 García-Torralba, Navarro Manzano, Luengo-Gil, De la Morena Barrio, Chaves Benito, Pérez-Ramos, Álvarez-Abril, Ivars Rubio, García-Garre, Ayala de la Peña and García-Martínez.)

Meat processing involves different transformations in the animal muscle after slaughtering, which results in changes in tenderness, aroma and colour, determining the quality of the final meat product. Enzymatic glycolysis, proteolysis and lipolysis play a key role in the conversion of muscle into meat. The accurate control of enzymatic reactions in meat muscle is complicated due to the numerous influential factors, as well as its low reaction rate. Moreover, exogenous enzymes are also used in the meat industry to produce restructured products (transglutaminase), to obtain bioactive peptides (peptides with antioxidant, antihypertensive and gastrointestinal activity) and to promote meat tenderization (papain, bromelain, ficin, zingibain, cucumisin and actinidin). Emerging technologies, such as ultrasound (US), pulsed electric fields (PEF), moderate electric fields (MEF), high-pressure processing (HPP) or supercritical CO 2 (SC-CO 2 ), have been used to intensify enzymatic reactions in different food applications. This review aims to provide an overview of the enzymatic reactions taking place during the processing of meat products, how they could be intensified by using emerging technologies and envisage potential applications.

Background: Obstructive sleep apnea syndrome is a common sleep-breathing disorder associated with adverse health outcomes including excessive daytime sleepiness, impaired quality of life and is well-established as a cardiovascular risk factor. Continuous positive airway pressure is the reference treatment, but its cardiovascular and metabolic benefits are still debated. Combined interventions aiming at improving patient's lifestyle behaviours are recommended in guidelines management of obstructive sleep apnea syndrome but adherence decreases over time and access to rehabilitation programmes is limited. Telerehabilitation is a promising approach to address these issues, but data are scarce on obstructive sleep apnea syndrome., Methods: The aim of this study is to assess the potential benefits of a telerehabilitation programme implemented at continuous positive airway pressure initiation, compared to continuous positive airway pressure alone and usual care, on symptoms and cardiometabolic risk factors of obstructive sleep apnea syndrome. This study is a 6-months multicentre randomized, parallel controlled trial during which 180 obese patients with severe obstructive sleep apnea syndrome will be included. We will use a sequential hierarchical criterion for major endpoints including sleepiness, quality of life, nocturnal systolic blood pressure and inflammation biological parameters., Discussion: m-Rehab obstructive sleep apnea syndrome is the first multicentre randomized controlled trial to examine the effectiveness of a telerehabilitation lifestyle programme in obstructive sleep apnea syndrome. We hypothesize that a telerehabilitation lifestyle intervention associated with continuous positive airway pressure for 6 months will be more efficient than continuous positive airway pressure alone on symptoms, quality of life and cardiometabolic risk profile. Main secondary outcomes include continuous positive airway pressure adherence, usability and satisfaction with the telerehabilitation platform and medico-economic evaluation., Trial Registration: Clinicaltrials.gov Identifier: NCT05049928. Registration data: 20 September 2021., Competing Interests: FB has received lecture fees or conference traveling grants from Lowenstein Medical, Bioprojet, Vitalaire, Sos Oxygene, Agir à dom, Bastide, ISIS Médical. DJ has received grants, lecture or consulting fees or conference traveling grants from Novartis, Sefam, Adene, Lowenstein, Nomics, GSK. JLP has received lecture or consulting or conference traveling grants from ResMed, Philips, Fisher and Paykel, AstraZeneca, Jazz Pharmaceutical, Agiradom, Mutualia, Vitalaire, Boehringer Ingelheim, Night Balance, Sefam. FG has received lecture or consulting or conference traveling grants from ResMed, Jazz Pharmaceutical, Sefam, Bioprojet, Philips Respironics, Cidelec, Asten Santé. KA has board engagements with Sanofi Genzyme, GSK, Astra Zeneca. FR has speaking honoraria and board engagements with Abbott, Air Liquide, Bayer, Pfizer, Astra Zeneca, Servier, Boehringer, Vifor, Novartis, Novonordisk, YD has speaking honoraria and board engagements with UCB Pharma, JAZZ, Orexia, Bioprojet, Avadel, Idorsia and Takeda. MH has received research grants from Bastide Medical, which are not related to the current project; personal fees from AstraZeneca for participation to scientific lectures; financial support for congress participation from SOS Oxygène, Eole Santé, Boehringer Ingelheim, GlaxoSmithKline, and AstraZeneca; and hospitalities during local scientific meetings from ALK-Abelló, Actelion Pharmaceuticals France, Vifor Fresenius Medical Care Renal Pharma, Sanofi Aventis France, Novartis Pharma, LVL Medical Sud, Chiesi, and SOS Oxygene Mediterranee. Other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Rapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD risk loci near SNCA, GBA, TMEM175, INPP5F, and SCARB2. Expression analyses highlight SNCA-AS1 and potentially SCARB2 differential expression in different brain regions in RBD, with SNCA-AS1 further supported by colocalization analyses. Polygenic risk score, pathway analysis, and genetic correlations provide further insights into RBD genetics, highlighting RBD as a unique alpha-synucleinopathy subpopulation that will allow future early intervention., (© 2022. The Author(s).)

Porcine liver has a high nutritional value and is rich in proteins, minerals, and vitamins, making it an interesting co-product to alleviate the growing global demand for protein. The objective of this study was to analyze how the drying and defatting processes of porcine liver affect the physicochemical and techno-functional properties of its proteins. Two drying temperatures (40 and 70 °C) were studied, and dried samples were defatted using organic solvents. The drying process turned out to be an effective method for the stabilization of the protein fraction; however, when the drying temperature was high (70 °C), greater protein degradation was found compared to drying at a moderate temperature (40 °C). Regarding the defatting stage, it contributed to an improvement in certain techno-functional properties of the liver proteins, such as the foaming capacity (the average of the dried and defatted samples was 397% higher than the dried samples), with the degree of foaming stability in the liver dried at 40 °C and defatted being the highest (13.76 min). Moreover, the emulsifying capacity of the different treatments was not found to vary significantly (p > 0.05). Therefore, the conditions of the drying and defatting processes conducted prior to the extraction of liver proteins must be properly adjusted to maximize the stability, quality, and techno-functional properties of the proteins.

Background: Insomnia is a frequent complaint of patients with Parkinson's disease, and it negatively affects quality of life. Drugs that improve both sleep and parkinsonism would be of major benefit to patients with Parkinson's disease-related insomnia. We aimed to test the safety and efficacy of subcutaneous night-time only apomorphine infusion in patients with Parkinson's disease and insomnia., Methods: We did a randomised, multicentre, double-blind, placebo-controlled, crossover trial in 11 expert centres in Parkinson's disease and sleep centres in France. Participants aged 35-90 years with fluctuating Parkinson's disease and moderate to severe insomnia (Insomnia Severity Index score ≥15) were randomly assigned to either first receive night-time subcutaneous apomorphine (up to 5 mg/h) or matching placebo. Randomisation was done using a computer-generated plan in blocks of four, stratified by centre. This first intervention was followed by a 14-night washout period, then crossover to the other intervention. The treatment periods consisted of a 10-night titration phase followed by a 7-night fixed-dose phase. The dose was adjusted during the titration phase on the basis of a daily telephone call assessing sleep quality and treatment tolerability. The primary efficacy endpoint was the difference in Parkinson's disease sleep scale (PDSS) scores from the beginning to the end of each treatment period. Analysis was done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT02940912., Findings: Between Jan 31, 2017, and Jan 29, 2021, 46 participants were enrolled. 25 (54%) patients were randomly assigned to receive apomorphine first and 21 (46%) patients to receive placebo first. Mean change in PDSS score was significantly greater with night-time apomorphine infusion (15·18 [SD 24·34]) compared with placebo (5·23 [21·52]; treatment effect 9·95 [95% CI 0·88-19·03]; p=0·041). Adverse events were reported in 25 (54%) participants during the apomorphine period and in 17 (37%) participants during the placebo period (p=0·16). Apomorphine was associated with more frequent dizziness than was placebo (seven [15%] vs 0; p=0·041)., Interpretation: Subcutaneous night-time only apomorphine infusion improved sleep disturbances according to difference on PDSS score, with an overall safety profile consistent with previous studies in Parkinson's disease. This treatment might be useful to manage sleep disturbances in patients with advanced Parkinson's disease and moderate to severe insomnia., Funding: Orkyn and Aguettant Pharma., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests SLS has received travel grants from UCB Pharma. VCDC has served on a scientific advisory board for Jazz Pharma and received honoraria for speeches from Orkyn, Aguettant and LVL medical; received research support from Orkyn and Aguettant; and received travel grants from Orkyn and Aguettant. IA has received consultancy fees from IDORSIA Pharma, ONO Pharma, and Roche Pharma, and payment for a lecture by UCB Pharma. ER has served on scientific advisory boards for Orkyn, Aguettant, Merz-Pharma, and Allergan; received honoraria for speeches from Orkyn, Aguettant, Merz-Pharma, Everpharma, Elivie, and the International Parkinson and Movement Disorders Society; received research support from Merz-Pharma, Orkyn, Aguettant, Elivie, Ipsen, Allergan, Everpharma, Fondation Desmarest, AMADYS, Fonds de Dotation Brou de Laurière, ADCY5.org, Agence Nationale de la Recherche, and Societé Française de Médecine Esthétique; received travel grants from Vitalaire, PEPS development, Aguettant, Merz-Pharma, Ipsen, Merck, Orkyn, Elivie, Adelia Medical, Dystonia Medical Research Foundation, International Parkinson and Movement Disorders Society, European Academy of Neurology, and the International Association of Parkinsonism and Related Disorders. MA declares honoraria and travel grants from AbbVie, Teva, Merz, Orkyn, Aguettant, Actelion Pharmaceuticals, and Johnson and Johnson. PD has received support from UCB Pharma for attending a meeting, and speaker's honoraria from Roche. CA has received travel grants from Merz, and honoraria for presentations from Abbvie and Orkyn. LLV has received travel grants from UCB Pharma and Bioprojet. SD has received support for attending meetings from Aguettant, Orkyn, LVL, Homeperf, Elivie, and Boston Scientific; honoraria for presentations from Aguettant, Orkyn, LVL, Medtronic, Homeperf, Elivie, and Boston Scientific; and consulting fees from Aguettant, Orkyn, and Boston Scientific. DD has received consultancy fees for a scientific advisory board for Abbvie, Alterity, Orkyn, Air Liquide, Apopharma, Lundbeck, Everpharma, Boston Scientific, and the Cure Parkinson Trust; grants from the French Ministry of Health: projet hospitalier de recherche clinique grants; French Ministry of Research: ANR; European Preclinical Research: Coen; European Clinical Research: Horizon 2020, charities from France Parkinson, ARSLA Foundation; Foundations: University of Lille, CA; and has equity stake from InBrain Pharma; InVenis biotherapies. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

At odds with other solid tumors, epithelial ovarian cancer (EOC) is poorly sensitive to immune checkpoint inhibitors (ICIs), largely reflecting active immunosuppression despite CD8 + T cell infiltration at baseline. Accumulating evidence indicates that both conventional chemotherapeutics and targeted anticancer agents commonly used in the clinical management of EOC not only mediate a cytostatic and cytotoxic activity against malignant cells, but also drive therapeutically relevant immunostimulatory or immunosuppressive effects. Here, we discuss such an immunomodulatory activity, with a specific focus on molecular and cellular pathways that can be harnessed to develop superior combinatorial regimens for clinical EOC care., Competing Interests: Declaration of interests J.F. and R.S. are full-time employees of Sotio Biotech. I.V. has received consulting/advisory honoraria from AstraZeneca, Clovis Oncology Inc., Carrick Therapeutics, Deciphera Pharmaceuticals, Elevar Therapeutics, Roche, Genmab, GSK, Immunogen, Jazzpharma, Mersana, Millennium Pharmaceuticals, MSD, Novocure, Octimet Oncology, Oncoinvent, Sotio, Verastem Oncology, and Zentalis; and has performed contracted research for Amgen, Genmab, Oncoinvent, and Genmab. E.G.M. has held research contracts with Roche, has received consulting/advisory honoraria from AstraZeneca and Clovis, as well as speaker honoraria from GSK, AstraZeneca, MSD, Clovis, and Roche. L.G. has held research contracts with Lytix Biopharma and Phosplatin, and has received consulting/advisory honoraria from Boehringer Ingelheim, AstraZeneca, OmniSEQ, Onxeo, Sotio, The Longevity Labs, Inzen, and the Luke Heller TECPR2 Foundation. All other authors have no conflicts to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Subtle gait changes associated with idiopathic rapid eye movement sleep behavior disorder (iRBD) could allow early detection of subjects with future synucleinopathies., Objective: The aim of this study was to create a multiclass model, using statistical learning from probability distribution of gait parameters, to distinguish between patients with iRBD, healthy control subjects (HCs), and patients with Parkinson's disease (PD)., Methods: Gait parameters were collected in 21 participants with iRBD, 21 with PD, and 21 HCs, matched for age, sex, and education level. Lasso sparse linear regression explored gait features able to classify the three groups., Results: The final model classified iRBD from HCs and from patients with PD equally well, with 95% accuracy, 100% sensitivity, and 90% specificity., Conclusions: Gait parameters and a pretrained statistical model can robustly distinguish participants with iRBD from HCs and patients with PD. This could be used to screen subjects with future synucleinopathies in the general population and to identify a conversion threshold to PD. © 2022 International Parkinson and Movement Disorder Society., (© 2022 International Parkinson and Movement Disorder Society.)