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An in-vacuum minipole (short period) Insertion Device is described and discussed. The research was accomplished at LURE (Laboratoire pour l'Utilization du Rayonnement Electromagnetique), in Ile de France.

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Numerous studies have demonstrated the beneficial effect of Avène Thermal Spring Water (TSW) in dermatological diseases but the molecular mechanisms remain unknown. The objective of the present study was to evaluate the effect of Avène TSW on the morphological and molecular features related to the more advanced status of differentiation of human keratinocytes. Normal human keratinocytes (NHK) were differentiated in medium powder reconstituted with Avène TSW and assessed by RT-PCR and immunohistochemistry. Calcium entry was measured by a Fura-2 AM probe. TRPV6 channel were detected by immunohistochemistry, RT-PCR and western blot. Treatment of NHK with Avène TSW led to an enhanced constitutive calcium entry that resulted in the increased expression of involucrin and cytokeratins 1 and 10. This enhanced constitutive calcium entry in Avène TSW-treated keratinocytes was mediated by the TRPV6 calcium channel. Moreover, Avène TSW-mediated calcium entry was due to the increase in TRPV6 expression as well as the channel abundance at the cell membrane. An other mechanism of action of Avène TSW is described. Avène TSW treatment induced an enhanced constitutive calcium entry mediated by TRPV6 channel leading to the acceleration of human keratinocytes differentiation. [ABSTRACT FROM AUTHOR]

Objectives: To use growth mixture modelling (GMM) to identify subgroups of children with attention deficit hyperactive disorder (ADHD) who have different pharmacodynamic profiles in response to extended release methylphenidate as assessed in a laboratory classroom setting. Methods: GMM analysis was performed on data from the COMACS study (Comparison of Methylphenidates in the Analog Classroom Setting): a large ( n = 184) placebo-controlled cross-over study comparing three treatment conditions in the Laboratory School Protocol (with a 1.5-h cycle of attention and deportment assessments). Two orally administered, once-daily methylphenidate (MPH) bioequivalent formulations [Metadate CD[TM]/Equasym[TM] XL (MCD-EQXL) and Concerta XL (CON)] were compared with placebo (PLA). Results: Three classes of children with distinct severity profiles in the PLA condition were identified. For both MCD-EQXL and CON, the more severe their PLA symptoms the better, the children's response. However, the formulations produced different growth curves by class, with CON having essentially a flat profile for all three classes (i.e. no effect of PLA severity) and MCD-EQXL showing a marked decline in symptoms immediately post-dosing in the two most severe classes compared with the least severe. Comparison of daily doses matched for immediate-release (IR) components accounted for this difference. Conclusion: The results suggest considerable heterogeneity in the pharmacodynamics of MPH response by children with ADHD. When treatment response for near-equal, bioequivalent daily doses the two formulations was compared, marked differences were seen for children in the most severe classes with a strong curvilinear trajectory for MCD-EQXL related to the greater IR component. [ABSTRACT FROM AUTHOR]

En 2050, 279 millions d'individus souffriront d'arthrose de la main dans le monde. Les traitements actuels (AINS en topique, AINS oraux, Paracétamol) sont peu efficaces et, si la prescription n'est pas respectée, associés à des effets indésirables. L'étude FLEXOA avait comme objectif d'étudier l'efficacité sur les symptômes et la tolérance d'une combination d'extraits de CL et BS chez des sujets souffrant d'arthrose digitale. FLEXOA est une étude multicentrique, randomisée, contrôlée contre placebo, en double aveugle. Les sujets devaient avoir au moins 40 ans, un IMC ≤ 35 kg/m2, souffrir d'arthrose digitale répondant aux critères de l'American College of Rheumatology (ACR) et déclarer, à l'inclusion, une douleur persistante depuis plusieurs mois comprise entre 40 et 80 mm sur une Echelle Visuelle Analogique (EVA) de 100 mm. Les sujets recevaient chaque jour soit 2 comprimés (1 matin/1 le soir) d'extraits de CL/BS ou de placebo pendant 3 mois. Un comprimé de CBTIL contenait 237,35 mg (200,0 mg de curcumine) d'extrait sec de CL (CURTIL03), 51,3 mg (33,34 mg d'acides boswelliques) d'extrait sec de BS (BOSTIL01) et 1,4 mg de vitamine D3. Le critère de jugement principal était le changement de la douleur (EVA) entre l'inclusion et 3 mois de traitement. Les critères de jugement secondaires étaient l'évolution de la douleur (EVA), de la fonction (FIHOA), de la qualité de vie (SF-36), l'évaluation globale par le patient (PGA), l'état acceptable par le patient (Patient Acceptable Symptoms State (PASS), EVA < 40 mm), la force de préhension, la consommation d'antalgiques ainsi que la tolérance au traitement. L'analyse statistique a été réalisée sur les populations Intent-to-treat (ITT) en utilisant le logiciel SAS version 9,4 et and R version 3,6. La signification statistique correspondait à un niveau de confiance de 95 % et une valeur p < 0,05. 162 sujets ont été randomisés (ITT : n = 83 CBTIL ; n = 79 placebos) et 149 sujets ont terminé l'étude (PP : n = 75 CBTIL ; n = 74 placebos). La population ITT présentait à l'inclusion les caractéristiques démographiques et cliniques suivantes : âge moyen de 63 ± 8,6 ans, 76,5 % étaient des femmes, IMC moyen de 26,2 ± 4,07 kg/m2 et une EVA moyenne de 59,18 ± 12,00 mm. Après 3 mois de traitement, la diminution de l'EVA douleur dans la population ITT était significativement plus importante dans le groupe CBTIL que dans le groupe placebo (différence−7,29 mm, [−15,83 ;1,25], p = 0,034)). La différence entre les groupes était déjà significative après 1 mois de traitement (différence −6,22, [−13,21 ;0,77] ; p = 0,044). Le pourcentage de sujets atteignant le PASS (EVA < 40 mm) après 1 mois (CBTIL : 47,50 % vs Placebo : 28,95 %, p = 0,025) et 3 mois (CBTIL : 58,97 % vs placebo : 41,89 %, p = 0,049) de traitement était significativement plus élevé dans le groupe CBTIL que dans le groupe placebo. Une amélioration significative a été observée dans le groupe CBTIL par rapport au placebo pour les critères suivants : l'évaluation globale du patient(PGA), le score SF-36 douleur et sur la question de santé générale. Les autres variables n'étaient pas significativement différentes entre les deux groupes. Dans l'arthrose digitale, CBTIL diminuait significativement la douleur et améliorait l'état de santé général des sujets, sans induire d'effets indésirables. Vu la faible efficacité des traitements pharmacologiques proposés à ce jour et leur mauvaise tolérance à long terme, CBTIL est une option thérapeutique qui doit être envisagée chez les patients souffrant d'arthrose de la main. [ABSTRACT FROM AUTHOR]

In the current context of developing aromatic beers, our study aims at deciphering the chemical characterisation of cones from 39 wild hop genotypes collected in the North of France and replanted in an experimental hop farm, as well as 10 commercial and 3 heirloom varieties, using HS-SPME/GC-MS for the volatile compounds, UHPLC-UV for phenolic compound quantification, and UHPLC-IMS-HRMS for untargeted metabolomics. These analyses revealed a strong opposition between wild accessions and reference varieties, and an original chemical composition of some genotypes. 27 beers were produced with the same recipe, analysed by SBSE-GC-MS and evaluated by panellists. The unique difference relates to the hops to be assessed in order to determine their sensory profile. The different datasets were compared by OPLS-DA analysis in order to identify chemical markers which may influence the hop aromatic potential. Our results highlight the aromatic potential of some wild accessions, close to the commercial variety Cascade., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Lithium (Li) is recommended for long-term treatment of bipolar disorder (BD). However, its mechanism of action is still poorly understood. Induced pluripotent stem cell (iPSC)-derived brain organoids have emerged as a powerful tool for modeling BD-related disease mechanisms. We studied the effects of 1 mM Li treatment for 1 month in iPSC-derived human cortical spheroids (hCS) from 10 healthy controls (CTRL) and 11 BD patients (6 Li-responders, Li-R, and 5 Li non-treated, Li-N). At day 180 of differentiation, BD hCS showed smaller size, reduced proportion of neurons, decreased neuronal excitability and reduced neural network activity compared to CTRL hCS. Li rescued excitability of BD hCS neurons by exerting an opposite effect in the two diagnostic groups, increasing excitability in BD hCS and decreasing it in CTRL hCS. We identified 132 Li-associated differentially expressed genes (DEGs), which were overrepresented in sodium ion homeostasis and kidney-related pathways. Moreover, Li regulated secretion of pro-inflammatory cytokines and increased mitochondrial reserve capacity in BD hCS. Through long-term Li treatment of a human 3D brain model, this study partly elucidates the functional and transcriptional mechanisms underlying the clinical effects of Li, such as rescue of neuronal excitability and neuroprotection. Our results also underscore the substantial influence of treatment duration in Li studies. Lastly, this study illustrates the potential of patient iPSC-derived 3D brain models for precision medicine in psychiatry., (© 2023. The Author(s).)

This paper analyzes the variability of microplastics vertical distributions in the oceanic water column. Data were obtained from targeted sampling in the Bay of Marseille (France) and from a numerical simulation forced by realistic physical forcings. By fitting model and in-situ data in a simplified vertical dimension, three microplastics classes may be deduced: settling, buoyant and winter neutrally-buoyant microplastics. Buoyant microplastics are mainly concentrated at the surface but they can be mixed throughout the whole water column during episodes with strong winds and no water stratification, inducing an implicit underestimation of buoyant microplastics in surface sampling. Almost symmetrical to the distribution of buoyant microplastics, settling microplastics are mainly found at the bottom but they can sometimes reach the surface under the mixing conditions cited above. They could thus contribute to surface sampling. Winter neutrally-buoyant microplastics are more homogenously mixed during the winter but are under the stratified layers during summer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Understanding factors that impact prognosis for cancer patients have high clinical relevance for treatment decisions and monitoring of the disease outcome. Advances in artificial intelligence (AI) and digital pathology offer an exciting opportunity to capitalize on the use of whole slide images (WSIs) of hematoxylin and eosin (H&E) stained tumor tissue for objective prognosis and prediction of response to targeted therapies. AI models often require hand-delineated annotations for effective training which may not be readily available for larger data sets. In this study, we investigated whether AI models can be trained without region-level annotations and solely on patient-level survival data. We present a weakly supervised survival convolutional neural network (WSS-CNN) approach equipped with a visual attention mechanism for predicting overall survival. The inclusion of visual attention provides insights into regions of the tumor microenvironment with the pathological interpretation which may improve our understanding of the disease pathomechanism. We performed this analysis on two independent, multi-center patient data sets of lung (which is publicly available data) and bladder urothelial carcinoma. We perform univariable and multivariable analysis and show that WSS-CNN features are prognostic of overall survival in both tumor indications. The presented results highlight the significance of computational pathology algorithms for predicting prognosis using H&E stained images alone and underpin the use of computational methods to improve the efficiency of clinical trial studies., (© 2022. The Author(s).)

Objectives: To investigate a 6-month intervention with an olive leaf extract (OLE) on knee functionality and biomarkers of bone/cartilage metabolism and inflammation., Design: This randomized, double-blind, placebo-controlled, multi-centric trial included 124 subjects with knee pain or mobility issues. Subjects received twice a day one capsule of placebo or 125 mg OLE (Bonolive ™ , an OLE containing 50 mg of oleuropein) for 6 months. The co-primary endpoints were Knee injury and Osteoarthritis Outcome Score (KOOS) and serum Coll2-1NO2. The secondary endpoints were the subscales of the KOOS, knee pain VAS at rest and at walking, OARSI core set of performance-based tests and multiple inflammatory and bone or cartilage remodeling serum biomarkers and concentration of oleuropein's metabolites in urine., Results: At 6 months, OLE group was not efficient on global KOOS score, changes of inflammatory and cartilage remodeling biomarkers compared to placebo. Post hoc analyses demonstrated a large and significant treatment effect of OLE in a sub-group of subjects with high walking pain at baseline ( p  = 0.03). This was observed at 6 months for the global KOOS score, and each different subscale and for pain at walking ( p  = 0.02). OLE treatment was well tolerated., Conclusion: OLE was not effective on joint discomfort excepted in a sub-group of subjects with high pain at treatment initiation. As oleuropein is well tolerated, OLE can be used to relieve knee joint pain and enhance mobility in subjects with articular pain., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: YH is the founder and chairman of Artialis SA, a spin-off company of the University of Liège developing biomarkers. MNH, MB, NS, LP, and MS are employees of Société des produits Nestlé SA. ACH, BC, and LG are employees of the Artialis’company., (© The Author(s), 2022.)

While neurodevelopmental abnormalities have been associated with schizophrenia (SCZ), the role of astroglia in disease pathophysiology remains poorly understood. In the present study, we used a human induced pluripotent stem cell (iPSC)-derived astrocyte model to investigate the temporal patterns of astroglia differentiation during developmental stages critical for SCZ using RNA sequencing. The model generated astrocyte-specific gene expression patterns during differentiation that corresponded well to astroglia-specific expression signatures of in vivo cortical fetal development. Using this model we identified SCZ-specific expression dynamics, and found that SCZ-associated differentially expressed genes were significantly enriched in the medial prefrontal cortex, striatum, and temporal lobe, targeting VWA5A and ADAMTS19. In addition, SCZ astrocytes displayed alterations in calcium signaling, and significantly decreased glutamate uptake and metalloproteinase activity relative to controls. These results implicate novel transcriptional dynamics in astrocyte differentiation in SCZ together with functional changes that are potentially important biological components of SCZ pathology., (© 2021. The Author(s).)

Voltage imaging and "all-optical electrophysiology" in human induced pluripotent stem cell (hiPSC)-derived neurons have opened unprecedented opportunities for high-throughput phenotyping of activity in neurons possessing unique genetic backgrounds of individual patients. While prior all-optical electrophysiology studies relied on genetically encoded voltage indicators, here, we demonstrate an alternative protocol using a synthetic voltage sensor and genetically encoded optogenetic actuator that generate robust and reproducible results. We demonstrate the functionality of this method by measuring spontaneous and evoked activity in three independent hiPSC-derived neuronal cell lines with distinct genetic backgrounds., Competing Interests: ARM is a co-founder and has equity interest in TISMOO, a company dedicated to genetic analysis and brain organoid modeling focusing on therapeutic applications customized for autism spectrum disorder and other neurological disorders with genetic origins. The terms of this arrangement have been reviewed and approved by the University of California San Diego in accordance with its conflict of interest policies. The remaining 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 © 2021 Puppo, Sadegh, Trujillo, Thunemann, Campbell, Vandenberghe, Shan, Akkouh, Miller, Bloodgood, Silva, Dale, Einevoll, Djurovic, Andreassen, Muotri and Devor.)

Alteration of brain aerobic glycolysis is often observed early in the course of Alzheimer's disease (AD). Whether and how such metabolic dysregulation contributes to both synaptic plasticity and behavioral deficits in AD is not known. Here, we show that the astrocytic l-serine biosynthesis pathway, which branches from glycolysis, is impaired in young AD mice and in AD patients. l-serine is the precursor of d-serine, a co-agonist of synaptic NMDA receptors (NMDARs) required for synaptic plasticity. Accordingly, AD mice display a lower occupancy of the NMDAR co-agonist site as well as synaptic and behavioral deficits. Similar deficits are observed following inactivation of the l-serine synthetic pathway in hippocampal astrocytes, supporting the key role of astrocytic l-serine. Supplementation with l-serine in the diet prevents both synaptic and behavioral deficits in AD mice. Our findings reveal that astrocytic glycolysis controls cognitive functions and suggest oral l-serine as a ready-to-use therapy for AD., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Structural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. Here, we developed human cortical organoids that dynamically change cellular populations during maturation and exhibited consistent increases in electrical activity over the span of several months. The spontaneous network formation displayed periodic and regular oscillatory events that were dependent on glutamatergic and GABAergic signaling. The oscillatory activity transitioned to more spatiotemporally irregular patterns, and synchronous network events resembled features similar to those observed in preterm human electroencephalography. These results show that the development of structured network activity in a human neocortex model may follow stable genetic programming. Our approach provides opportunities for investigating and manipulating the role of network activity in the developing human cortex., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Optical methods that rely on fluorescence for mapping changes in neuronal membrane potential in the brains of awake animals provide a powerful way to interrogate the activity of neurons that underlie neural computations ranging from sensation and perception to learning and memory. To achieve this goal, fluorescent indicators should be bright, highly sensitive to small changes in membrane potential, nontoxic, and excitable with infrared light. We report a new class of fluorescent, voltage-sensitive dyes: sulfonated rhodamine voltage reporters (sRhoVR), synthetic fluorophores with high voltage sensitivity, excellent two-photon performance, and compatibility in intact mouse brains. sRhoVR dyes are based on a tetramethyl rhodamine fluorophore coupled to a phenylenevinylene molecular wire/diethyl aniline voltage-sensitive domain. When applied to cells, sRhoVR dyes localize to the plasma membrane and respond to membrane depolarization with a fluorescence increase. The best of the new dyes, sRhoVR 1, displays a 44% Δ F / F increase in fluorescence per 100 mV change, emits at 570 nm, and possesses excellent two-photon absorption of approximately 200 GM at 840 nm. sRhoVR 1 can detect action potentials in cultured rat hippocampal neurons under both single- and two-photon illumination with sufficient speed and sensitivity to report on action potentials in single trials, without perturbing underlying physiology or membrane properties. The combination of speed, sensitivity, and brightness under two-photon illumination makes sRhoVR 1 a promising candidate for in vivo imaging in intact brains. We show sRhoVR powerfully complements electrode-based modes of neuronal activity recording in the mouse brain by recording neuronal transmembrane potentials from the neuropil of layer 2/3 of the mouse barrel cortex in concert with extracellularly recorded local field potentials (LFPs). sRhoVR imaging reveals robust depolarization in response to whisker stimulation; concurrent electrode recordings reveal negative deflections in the LFP recording, consistent with the canonical thalamocortical response. Importantly, sRhoVR 1 can be applied in mice with chronic optical windows, presaging its utility in dissecting and resolving voltage dynamics using two-photon functional imaging in awake, behaving animals., Competing Interests: The authors declare the following competing financial interest(s): EWM is listed as an inventor on a patent owned by UC Regents for voltage-sensitive fluorophores.

Recent advances in optical technologies such as multi-photon microscopy and optogenetics have revolutionized our ability to record and manipulate neuronal activity. Combining optical techniques with electrical recordings is of critical importance to connect the large body of neuroscience knowledge obtained from animal models to human studies mainly relying on electrophysiological recordings of brain-scale activity. However, integration of optical modalities with electrical recordings is challenging due to generation of light-induced artifacts. Here we report a transparent graphene microelectrode technology that eliminates light-induced artifacts to enable crosstalk-free integration of 2-photon microscopy, optogenetic stimulation, and cortical recordings in the same in vivo experiment. We achieve fabrication of crack- and residue-free graphene electrode surfaces yielding high optical transmittance for 2-photon imaging down to ~ 1 mm below the cortical surface. Transparent graphene microelectrode technology offers a practical pathway to investigate neuronal activity over multiple spatial scales extending from single neurons to large neuronal populations.

An appropriate medication management depends on executive system integrity, which can be affected by aging. Previous studies showed that seniors commit frequent errors when having to fill in a pillbox. Nevertheless, to the best of our knowledge, no study has really considered the absence of cognitive disorders in the studied sample. The present study aimed to investigate pillbox filling in cognitively healthy elderly (specially focusing on executive system preservation) for whom no cognitive deterioration neither any depressive episode had occurred during a one year period. The filling task has been completed using a weekly pillbox and eight fictitious drugs. The selection of the 27 seniors aged from 71 to 90 years has been based on their results to neuropsychological tests (Trail making test, Stroop Victoria, Tower of London, Montreal cognitive assessment) and a depression assessment scale (Short geriatric depression scale). Results showed that 67% of the participants committed at least one error when filling the pillbox and 56% at least 3. The maximal number of errors was 38. Further, the errors analysis showed that 85% of the errors had been repeated (e.g. reproduced on several days). Finally, the more complex the drug prescriptions are, the higher the error rate is. No other variable (age, gender, level education, habit of filling a pillbox) had any effect on the number of errors. So, the pillbox filing task can be considered as a complex task associated with a high risk of errors. Moreover, the absence of cognitive disorders is not a success factor to the task. A prospect for the future should be to try to limit the error rate by developing, for instance, an external support helping to the filling of the pillbox and a learning process for the use of this support.

The computational properties of the human brain arise from an intricate interplay between billions of neurons connected in complex networks. However, our ability to study these networks in healthy human brain is limited by the necessity to use non-invasive technologies. This is in contrast to animal models where a rich, detailed view of cellular-level brain function with cell-type-specific molecular identity has become available due to recent advances in microscopic optical imaging and genetics. Thus, a central challenge facing neuroscience today is leveraging these mechanistic insights from animal studies to accurately draw physiological inferences from non-invasive signals in humans. On the essential path towards this goal is the development of a detailed 'bottom-up' forward model bridging neuronal activity at the level of cell-type-specific populations to non-invasive imaging signals. The general idea is that specific neuronal cell types have identifiable signatures in the way they drive changes in cerebral blood flow, cerebral metabolic rate of O2 (measurable with quantitative functional Magnetic Resonance Imaging), and electrical currents/potentials (measurable with magneto/electroencephalography). This forward model would then provide the 'ground truth' for the development of new tools for tackling the inverse problem-estimation of neuronal activity from multimodal non-invasive imaging data.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'., (© 2016 The Author(s).)

Distal biceps tendon ruptures are relatively rare. Patients are usually middle-aged men involved in heavy labor. Patients usually present with the history of a pop and a proximal migration of the biceps muscle belly. Clinical exam should be sufficient to diagnose a complete rupture. Several specific tests have been described. Ultrasound scanning or MRI can help confirm the diagnosis. Radiographs are not needed to diagnose distal biceps tendon rupture but may show typical findings. Imaging, more specifically the flexion-abduction-supination (FABS) view MRI, is particularly helpful in the case of a partial rupture or chronic rupture of the distal biceps tendon. Results of surgical reinsertion of the distal biceps have been shown to be superior to conservative treatment. Different techniques and approaches have been described with specific advantages and disadvantages. Primary repair of the tendon is preferred. If this is no longer possible in chronic tears, an augmentation can be done using tendon graft. Results of surgical treatment are good in the vast majority of patients. Reruptures are rare but minor complications are common. Major complications may include posterior interosseous nerve palsy or radioulnar synostosis, but the risk of these complications may be decreased by meticulous attention to detail during surgery.

Identification of the cellular players and molecular messengers that communicate neuronal activity to the vasculature driving cerebral hemodynamics is important for (1) the basic understanding of cerebrovascular regulation and (2) interpretation of functional Magnetic Resonance Imaging (fMRI) signals. Using a combination of optogenetic stimulation and 2-photon imaging in mice, we demonstrate that selective activation of cortical excitation and inhibition elicits distinct vascular responses and identify the vasoconstrictive mechanism as Neuropeptide Y (NPY) acting on Y1 receptors. The latter implies that task-related negative Blood Oxygenation Level Dependent (BOLD) fMRI signals in the cerebral cortex under normal physiological conditions may be mainly driven by the NPY-positive inhibitory neurons. Further, the NPY-Y1 pathway may offer a potential therapeutic target in cerebrovascular disease.

Introduction: Early damage to episodic memory encoding and consolidation processes has been demonstrated in dementia of the Alzheimer type. However, in the domain of verbal episodic memory assessment, there are few diagnostic tools adapted to the old and oldest old as far as ease of administration and accuracy of normative data are concerned. Classic tasks are either too effortful (like the free recall/cued recall of 16 items), not sensitive enough (like the 5 words test), or insufficiently accurate for people above 70 years old in terms of normative data., Aim: The aim of this study was to develop a reduced task (in terms of number of items and number of trials) assessing verbal episodic memory in people aged between 70 and 89 years old., Methods: The task (GERIA-12) used the same procedure as the RL/RI-16 task but the list comprised only 12 words and there were only 2 learning trials. In order to assess consolidation processes, we included 2 delayed recall trials, one after 20 minutes and the other after 24 hours. We also calculated indexes adapted from the Item-Specific Deficit Approach developed by Wright et al., which has the advantage of providing measures specific to encoding, consolidation and retrieval processes. Standardization was done with data from 220 people aged between 70 and 89 years old and belonging to 3 education levels., Results: We obtained a significant effect of age and education level: scores decrease with age and increase with education. Norms have thus been calculated taking those two variables into consideration. Concerning the standardization, Barona method has been used for free recall scores while percentiles have been used for all other scores (total recall, free recall, encoding, consolidation and retrieval indexes). Normative data are also provided for intrusions and perseverations., Conclusion: This new task allows encoding, consolidation and retrieval processes assessment in older people and has the following advantages: the procedure is more suitable (ease and time of administration), there are accurate normative data for old and oldest old people, and there are normative data for two delayed recalls (at 20 minutes and at 24 hours)., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Deviation of the ambient temperature is one of the most ubiquitous stimuli that continuously affect mammals' skin. Although the role of the warmth receptors in epidermal homeostasis (EH) was elucidated in recent years, the mystery of the keratinocyte mild-cold sensor remains unsolved. Here we report the cloning and characterization of a new functional epidermal isoform of the transient receptor potential M8 (TRPM8) mild-cold receptor, dubbed epidermal TRPM8 (eTRPM8), which is localized in the keratinocyte endoplasmic reticulum membrane and controls mitochondrial Ca(2+) concentration ([Ca(2+)]m). In turn, [Ca(2+)]m modulates ATP and superoxide (O2(·-)) synthesis in a cold-dependent manner. We report that this fine tuning of ATP and O2(·-) levels by cooling controls the balance between keratinocyte proliferation and differentiation. Finally, to ascertain eTRPM8's role in EH in vivo we developed a new functional knockout mouse strain by deleting the pore domain of TRPM8 and demonstrated that eTRPM8 knockout impairs adaptation of the epidermis to low temperatures.

Introduction. Bicompartmental knee arthroplasty (BKA) addresses combined medial and patellofemoral compartment osteoarthritis, which is relatively common, and has been proposed as a bridge between unicompartmental and total knee arthroplasty (TKA). Case Presentation. We present the case report of a young active man treated with BKA after unsuccessful conservative therapy. Four years later, loosening with fracture of the tibial baseplate was identified and the patient was revised to TKA. Discussion. Although our case is only the second fractured tibial baseplate to be reported, we believe that the modular titanium design, with two fixation pegs, is too thin to withstand daily cyclic loading powers. Light daily routine use, rather than high-impact sports, is therefore advised. Failures may also be related to the implant being an early generation and known to be technically complex, with too few implant sizes. We currently use TKA for the treatment of medial and patellofemoral compartment osteoarthritis.

Transient receptor potential vanilloid subfamily member 6 (TRPV6) is a highly selective calcium channel that has been considered as a part of store-operated calcium entry (SOCE). Despite its first discovery in the early 2000s, the role of this channel in prostate cancer (PCa) remained, until now, obscure. Here we show that TRPV6 mediates calcium entry, which is highly increased in PCa due to the remodeling mechanism involving the translocation of the TRPV6 channel to the plasma membrane via the Orai1/TRPC1-mediated Ca(2+)/Annexin I/S100A11 pathway, partially contributing to SOCE. The TRPV6 calcium channel is expressed de novo by the PCa cell to increase its survival by enhancing proliferation and conferring apoptosis resistance. Xenografts in nude mice and bone metastasis models confirmed the remarkable aggressiveness of TRPV6-overexpressing tumors. Immunohistochemical analysis of these demonstrated the increased expression of clinical markers such as Ki-67, prostate specific antigen, synaptophysin, CD31, and CD56, which are strongly associated with a poor prognosis. Thus, the TRPV6 channel acquires its oncogenic potential in PCa due to the remodeling mechanism via the Orai1-mediated Ca(2+)/Annexin I/S100A11 pathway.