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Background: The prevalence of HIV-associated neurocognitive disorders (HAND) remains high despite antiretroviral treatment (ART). Changes in gut microbiota and persistent immune activation have been suggested as possible causes, while the role of probiotic supplementation remains controversial. Methods: We included subjects with mild HAND and successful ART. They were randomized to receive either 6 months of high-dose probiotic supplementation or to continue with only ART. Immune activation markers and neuropsychological testing were performed at baseline and the end of follow-up. Neuropsychological testing assessed learning, episodic memory, attention/concentration, executive functions, language, information processing speed, and motor skills. Z- and T-scores were calculated for all domains but motor skills, allowing the measurement of the global deficit score (GDS). The trajectories of neuropsychological performances and immune activation markers were compared between groups. Results: From September 2020 to July 2021, 31 PWHs were included (median age 62, 73% men, CD4 744 cc/mm3), and 28 completed the 6-month follow-up. The characteristics of the subjects and their neuropsychological performance at baseline in the two groups were similar. At the end of follow-up, probiotics did not have any impact on immune activation markers, while they were associated with better improvement in GDS (T-score 0.0 in controls vs. −0.3 in probiotics, p = 0.048) and the attention/concentration test (Z-score 0.4 in controls vs. 1.2 in probiotics, p = 0.035). Conclusions: Oral supplementation with high-dose probiotics for 6 months did not affect systemic immune activation but was associated with improved neurocognitive performance, suggesting benefits from probiotic supplementation for mild HAND.

BackgroundNMF are currently poorly evaluated in therapeutic decisions. A quantification of their severity would facilitate their integration. The objective of this study was to validate an autoquestionnaire evaluating the severity of non-motor fluctuations (NMF) in Parkinson’s disease (PD).MethodsPatients with PD were included in presurgical situation for deep brain stimulation of subthalamic nuclei. They participated in the PREDISTIM cohort (a study evaluating the predictive factors for therapeutic response of subthalamic stimulation in PD) in 17 centres in France. Our questionnaire, resulting from previous phases of development, included 11 non-motor symptoms (NMS). Their severity ranged from 0 to 10 and was assessed in OFF and then ON-Dopa to study their fluctuations.Results310 patients were included, of whom 98.8% had NMS and 98.0% had NMF. Each NMS was significantly improved by L-Dopa (decrease in severity score ranging from 43.1% to 69.9%). Fatigue was the most frequent and most severe NMS. NMS were considered more bothersome than motor symptoms by 37.5% of patients in OFF-Dopa and 34.9% in ON-Dopa.ConclusionsThis is the first questionnaire allowing a real-time quantification of the severity of NMS and their fluctuation with levodopa. It was able to confirm and measure the effect of L-dopa and show differences according to the patients and the NMS. It differs from other questionnaires by its measurement at a precise moment of the severity of the NMS, allowing its use during pretherapeutic assessments.Our questionnaire has been validated to measure the severity of NMF. It will be able to quantify the non-motor effect of anti-parkinsonian treatments and could facilitate the integration of NMF in therapeutic decisions.

Introduction Cognitive impairment in multiple sclerosis (MS) is common even in the early stages of the disease. Our objective was to improve early detection of cognitive impairment in MS. Methods Seventy-five patients with relapsing remitting (RR) MS and 20 controls were enrolled. Two RRMS groups were defined according to their results at the Paced Auditory Serial Addition Test (PASAT). Patients with a z score below two standard deviations were considered impaired. We quantified T2 and T1 lesion volumes, and cerebral white and grey matter volumes on a conventional brain magnetic resonance imaging (MRI) scan. Global brain atrophy was evaluated using the third ventricle (V3) width (in mm). An average brain model was built based on controls and compared with the patient’s MRI to quantify regional volumetric changes. Results Sixteen (21.3%) patients with RRMS had low PASAT performance. They had a higher Expanded Disability Status Scale (EDSS) score ( P  = 0.019). T2 and T1 lesion volumes, and grey and white matter volumes were the same in both groups. An enlargement of the V3 width was observed in the low performer group ( P  = 0.044) and V3 width was correlated with the PASAT score ( r  = −0.271; P  = 0.021). A composite score, named HV3, was obtained by adding the EDSS and V3 width (in mm) and correlated with the PASAT ( r  = −0.325; P  = 0.006). A cutoff HV3 score of over 5.5 identified patients with low PASAT performance, with a positive predictive value of 92.5% and an accuracy of 70.1%. Focal atrophy was detected in the supplementary motor area, the cingulate gyrus, the right thalamus, and the inferior parietal lobules of patients with lower PASAT performance. Conclusion Specific brain morphological changes, including an enlargement of the V3 width, are associated with low PASAT performance in patients with RRMS. The HV3 score is an additional and complementary tool, accessible in clinical practice, to suspect easily cognitive impairment in patients with RRMS and to better identify patients requiring a complete cognitive assessment.

Background Germ cell tumors and sex cord stromal tumors are rare cancers of the ovary. They mainly affect young women and are associated with a high survival rate. The standard treatment mainly involves conservative surgery combined with chemotherapy [bleomycin, etoposide and cisplatin (BEP)] depending on the stage and the prognostic factors, as for testicular cancers. As reported in testicular cancer survivors, chemotherapy may induce sequelae impacting quality of life, which has not yet been evaluated in survivors of germ cell tumors and sex cord stromal tumors. The GINECO-VIVROVAIRE-Rare tumor study is a two-step investigation aiming to assess i) chronic fatigue and quality of life and ii) long-term side-effects of chemotherapy with a focus on cardiovascular and pulmonary disorders. Methods Using self-reported questionnaires, chronic fatigue and quality of life are compared between 134 ovarian cancer survivors (cancer-free ≥2 years after treatment) treated with surgery and chemotherapy and 2 control groups (67 ovarian cancer survivors treated with surgery alone and 67 age-matched healthy women). Medical data are collected from patient records. In the second step evaluating the long-term side-effects of chemotherapy, a subgroup of 90 patients treated with chemotherapy and 45 controls undergo the following work-up: cardiovascular evaluation (clinical examination, non-invasive cardiovascular tests to explore heart disease, blood tests), pulmonary function testing, audiogram, metabolic and hormonal blood tests. Costs of sequelae will be also assessed. Patients are selected from the registry of the INCa French Network for Rare Malignant Ovarian Tumors, and healthy women by the ‘Seintinelles’ connected network (collaborative research platform). Discussion This study will provide important data on the potential long-term physical side-effects of chemotherapy in survivors of Germ Cell Tumors (GCT) and Sex Cord Stromal Tumors (SCST), especially cardiovascular and pulmonary disorders, and neurotoxicity. The identification of long-term side-effects can contribute to adjusting the treatment of ovarian GCT or SCST patients and to managing follow-up with adapted recommendations regarding practices and chemotherapy regimens, in order to reduce toxicity while maintaining efficacy. Based on the results, intervention strategies could be proposed to improve the management of these patients during their treatment and in the long term. Trial registration This trial was registered at clinicaltrials.gov : 03418844 , on 1 February 2018. This trial was registered on 25 October 2017 under the unique European identification number (ID-RCB): 2017-A03028–45. Recruitment Status: Recruiting. Protocol version Version n° 4.2 dated from Feb 19, 2021. Trial sponsor Centre François Baclesse, 3 avenue du Général Harris, F-14076 Caen cedex 05, France.

The craniate head is innervated by cranial sensory and motor neurons. Cranial sensory neurons stem from the neurogenic placodes and neural crest and are seen as evolutionary innovations crucial in fulfilling the feeding and respiratory needs of the craniate \"new head.\" In contrast, cranial motoneurons that are located in the hindbrain and motorize the head have an unclear phylogenetic status. Here we show that these motoneurons are in fact homologous to the motoneurons of the sessile postmetamorphic form of ascidians. The motoneurons of adult Ciona intestinalis, located in the cerebral ganglion and innervating muscles associated with the huge \"branchial basket,\" express the transcription factors CiPhox2 and CiTbx20, whose vertebrate orthologues collectively define cranial motoneurons of the branchiovisceral class. Moreover, Ciona's postmetamorphic motoneurons arise from a hindbrain set aside during larval life and defined as such by its position (caudal to the prosensephalic sensory vesicle) and coexpression of CiPhox2 and CiHoxl, whose orthologues collectively mark the vertebrate hindbrain. These data unveil that the postmetamorphic ascidian brain, assumed to be a derived feature, in fact corresponds to the vertebrate hindbrain and push back the evolutionary origin of cranial nerves to before the origin of craniates.

Given the very recent investment in research on organic rabbit production, many knowledge gaps remain. Simulation models based on data from experiments and farms may help generate general principles for organic rabbit production. Our goals were to (i) develop a model to simulate intake regulation and growth of rabbits raised on pastures, (ii) validate this model under a diversity of conditions and (iii) conduct a simulation experiment to predict the potential to decrease the supply of complete feed by increasing the grazing area per rabbit. The model developed (PASTRAB) simulates organic rabbit fattening on pastures in four main submodels that represent dynamics of (i) herbage standing biomass, fill and feed values; (ii) intake of herbage, complementary feed (i.e. complete pellets, cereal–legume grain mixtures) and hay as regulated by herbage allowance, fill and feed values of feedstuffs and rabbit physiological parameters; (iii) conversion of rabbit intake into live weight gain; and (iv) rabbit mortality. The model also calculates gross margin per rabbit sold. Model accuracy was assessed by considering the fit between observed and predicted herbage intake, which was low, with a relative root mean square error (rRMSE) of 51% and 66% on grass-based and legume-based pastures, respectively. However, the standard deviations of observed herbage intake were similar to the root mean square error of predicted herbage intake, indicating that it would have been difficult to improve model calibration. The fit between observed and predicted rabbit live weight was acceptable, with an rRMSE of 11% and 10% for grass-based and legume-based pastures, respectively. Simulated scenarios showed that a decrease in complementary feed combined with an increase in the grazing area per rabbit had little impact on average daily growth and gross margin per rabbit but increased herbage use efficiency. With 90 g of complementary feed per day and grazing of 0.4 m²/rabbit per day, herbage use efficiency was 22%, with average daily growth of 21.6 g/day and gross margin of 18.80 €/rabbit. With no complementary feed and grazing of 1.2 m²/rabbit per day, average daily growth decreased (19.2 g/day), but herbage use efficiency reached 100% and gross margin reached 19.20 €/rabbit. We used PASTRAB in participatory workshops with farmers so that the latter could explore adaptations to their current practices. Overall, farmers considered the model predictions realistic, and some of them decided to adapt some of their management practices immediately after the workshops.

Given the very recent investment in research on organic rabbit production, many knowledge gaps remain. Simulation models based on data from experiments and farms may help generate general principles for organic rabbit production. Our goals were to (i) develop a model to simulate intake regulation and growth of rabbits raised on pastures, (ii) validate this model under a diversity of conditions and (iii) conduct a simulation experiment to predict the potential to decrease the supply of complete feed by increasing the grazing area per rabbit. The model developed (PASTRAB) simulates organic rabbit fattening on pastures in four main submodels that represent dynamics of (i) herbage standing biomass, fill and feed values; (ii) intake of herbage, complementary feed (i.e. complete pellets, cereal–legume grain mixtures) and hay as regulated by herbage allowance, fill and feed values of feedstuffs and rabbit physiological parameters; (iii) conversion of rabbit intake into live weight gain; and (iv) rabbit mortality. The model also calculates gross margin per rabbit sold. Model accuracy was assessed by considering the fit between observed and predicted herbage intake, which was low, with a relative root mean square error (rRMSE) of 51% and 66% on grass-based and legume-based pastures, respectively. However, the standard deviations of observed herbage intake were similar to the root mean square error of predicted herbage intake, indicating that it would have been difficult to improve model calibration. The fit between observed and predicted rabbit live weight was acceptable, with an rRMSE of 11% and 10% for grass-based and legume-based pastures, respectively. Simulated scenarios showed that a decrease in complementary feed combined with an increase in the grazing area per rabbit had little impact on average daily growth and gross margin per rabbit but increased herbage use efficiency. With 90 g of complementary feed per day and grazing of 0.4 m²/rabbit per day, herbage use efficiency was 22%, with average daily growth of 21.6 g/day and gross margin of 18.80€ /rabbit. With no complementary feed and grazing of 1.2 m²/rabbit per day, average daily growth decreased (19.2 g/day), but herbage use efficiency reached 100% and gross margin reached 19.20€ /rabbit. We used PASTRAB in participatory workshops with farmers so that the latter could explore adaptations to their current practices. Overall, farmers considered the model predictions realistic, and some of them decided to adapt some of their management practices immediately after the workshops.