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Caffeine consumption outcomes on Amyotrophic Lateral Sclerosis (ALS) including progression, survival and cognition remain poorly defined and may depend on its metabolization influenced by genetic variants. 378 ALS patients with a precise evaluation of their regular caffeine consumption were monitored as part of a prospective multicenter study. Demographic, clinical characteristics, functional disability as measured with revised ALS Functional Rating Scale (ALSFRS-R), cognitive deficits measured using Edinburgh Cognitive and Behavioural ALS Screen (ECAS), survival and riluzole treatment were recorded. 282 patients were genotyped for six single nucleotide polymorphisms tagging different genes involved in caffeine intake and/or metabolism: CYP1A1 (rs2472297), CYP1A2 (rs762551), AHR (rs4410790), POR (rs17685), XDH (rs206860) and ADORA2A (rs5751876) genes. Association between caffeine consumption and ALSFRS-R, ALSFRS-R rate, ECAS and survival were statistically analyzed to determine the outcome of regular caffeine consumption on ALS disease progression and cognition. No association was observed between caffeine consumption and survival (p = 0.25), functional disability (ALSFRS-R; p = 0.27) or progression of ALS (p = 0.076). However, a significant association was found with higher caffeine consumption and better cognitive performance on ECAS scores in patients carrying the C/T and T/T genotypes at rs2472297 (p-het = 0.004). Our results support the safety of regular caffeine consumption on ALS disease progression and survival and also show its beneficial impact on cognitive performance in patients carrying the minor allele T of rs2472297, considered as fast metabolizers, that would set the ground for a new pharmacogenetic therapeutic strategy.

With this manuscript we aim to initiate a discussion specific to educational actions around ultrasonics sonochemistry. The importance of these actions does not just derive from a mere pedagogical significance, but they can be an exceptional tool for illustrating various concepts in other disciplines, such as process intensification and microfluidics. Sonochemistry is currently a far-reaching discipline extending across different scales of applicability, from the fundamental physics of tiny bubbles and molecules, up to process plants. This review is part of a special issue in Ultrasonics Sonochemistry, where several scholars have shared their experiences and highlighted opportunities regarding ultrasound as an education tool. The main outcome of our work is that teaching and mentorship in sonochemistry are highly needed, with a balanced technical and scientific knowledge to foster skills and implement safe protocols. Applied research typically features the use of ultrasound as ancillary, to merely enhance a given process and often leading to poorly conceived experiments and misunderstanding of the actual effects. Thus, our scientific community must build a consistent culture and monitor reproducible practices to rigorously generate new knowledge on sonochemistry. These practices can be implemented in teaching sonochemistry in classrooms and research laboratories. We highlight ways to collectively provide a potentially better training for scientists, invigorating academic and industry-oriented careers. A salient benefit for education efforts is that sonochemistry-based projects can serve multidisciplinary training, potentially gathering students from different disciplines, such as physics, chemistry and bioengineering. Herein, we discuss challenges, opportunities, and future avenues to assist in designing courses and research programs based on sonochemistry. Additionally, we suggest simple experiments suitable for teaching basic physicochemical principles at the undergraduatelevel. We also provide arguments and recommendations oriented towards graduate and postdoctoral students, in academia or industry to be more entrepreneurial. We have identified that sonochemistry is consistently seen as a ‘green’ or sustainable tool, which particular appeal to process intensification approaches, including microfluidics and materials science. We conclude that a globally aligned pedagogical initiative and constantly updated educational tools will help to sustain a virtuous cycle in STEM and industrial applications of sonochemistry.

This paper reports the preparation and herbicidal evaluation of a small library of acylhydrazones based on the synthetic herbicide metribuzin. The hydrazone linkage easily obtained by reaction of metribuzin with aliphatic and aromatic aldehydes, masks efficiently the exocyclic amino group, thereby altering significantly H-bonding with the receptor and increasing the lipophilicity relative to the parent herbicide. The structures of all compounds, including key stereochemical issues on conformation and E/Z configuration around the CN bond were thoroughly elucidated by spectroscopic methods, and unambiguously corroborated by X-ray diffraction analysis. The herbicidal assays using an aliphatic and an aromatic acylhydrazone were performed on tomato and rapeseed plants grown in greenhouse. Our results demonstrate, regardless of rate application, that such acylhydrazone formulations do not alter the selectivity of metribuzin. Moreover, the herbicide activity was even higher in the alkyl derivative than that achieved by commercial metribuzin, thus suggesting that this substance can be applied with no need of combination with chemical coadjuvants, unlike most formulations of commercially available herbicides. Therefore, the study shows the promising effect of chemical derivatization of a common herbicide as metribuzin, to improve the herbicide activity without compromising selectivity, and allowing the farmers its use in crop protection safely and effectively.

Crop type maps are essential for a wide range of applications such as crop monitoring, and yield estimation. In addition, Earth Observation (EO) systems allow robust and timely mapping of the earth’s surface, usually based on time-series. Yet, existing crop type maps are either global at coarse spatial resolution, or have a local or regional scope. The reasons for this gap can be linked to the scarcity of global crop type datasets at field level to train the models, their bias towards the Northern Hemisphere, as well as the limited transferability of existing crop type models across different regions. One of the main limitations on the transferability is driven by the phenological shift of the crops’ radiometric time series detected by Earth Observation (EO) systems, which is mainly induced by the different climates across regions. In this study, we explore the normalization of EO-based wheat time series with the accumulation of Growing Degree Days (GDD): the Thermo-RAdiometric Normalization of Crop Observations (TRANCO) system. The TRANCO system is based on the assumption that crop phenology evolution is mainly driven by temperature accumulation, represented by the accumulated GDD from Start of Season (SOS) to End of Season (EOS) dates, derived from a crop calendar. We tested the proposed method to normalize wheat on a database of globally distributed samples, whose results show a great improvement of the GDD F1 score (0.90) compared to a simpler normalization approach based on Time windows defined from SOS calendars (0.87) and a baseline without normalization (0.83).

Background & Aims: Transforming growth factor beta (TGFβ) acts either as a tumor suppressor or as an oncogene, depending on the cellular context and time of activation. TGFβ activates the canonical SMAD pathway through its interaction with the serine/threonine kinase type I and II heterotetrameric receptors. Previous studies investigating TGFβ-mediated signaling in the pancreas relied either on loss-of-function approaches or on ligand overexpression, and its effects on acinar cells have so far remained elusive. Methods: We developed a transgenic mouse model allowing tamoxifen-inducible and Cre-mediated conditional activation of a constitutively active type I TGFβ receptor (TβRICA) in the pancreatic acinar compartment. Results: We observed that TβRICA expression induced acinar-to-ductal metaplasia (ADM) reprogramming, eventually facilitating the onset of KRASG12D-induced pre-cancerous pancreatic intraepithelial neoplasia. This phenotype was characterized by the cellular activation of apoptosis and dedifferentiation, two hallmarks of ADM, whereas at the molecular level, we evidenced a modulation in the expression of transcription factors such as Hnf1β, Sox9, and Hes1. Conclusions: We demonstrate that TGFβ pathway activation plays a crucial role in pancreatic tumor initiation through its capacity to induce ADM, providing a favorable environment for KRASG12D-dependent carcinogenesis. Such findings are highly relevant for the development of early detection markers and of potentially novel treatments for pancreatic cancer patients. Keywords: Pancreas, Cancer, TGFβ, Acinar-to-Ductal Metaplasia, KRASG12D

Objetivos: Explorar la perspectiva de los usuarios y analizar los factores que influyen en su vinculación en un programa de reducción de daños (REDAN) que presta los siguientes servicios: intercambio de jeringuillas, espacio educativo de calor y café, programa de mantenimiento con metadona, sala de consumo higiénico supervisado, espacio para la higiene personal y seguimiento sanitario y psicosocial. Este programa presenta la particularidad de estar integrado en un ambulatorio de drogodependencias situado en un recinto hospitalario. Métodos: Estudio descriptivo realizado con metodología cualitativa. Se realizó un muestreo teórico. Se saturaron los contenidos mediante 12 entrevistas en profundidad y un grupo focal con ocho participantes. El análisis de la información se basó en la Grounded Theory. Las transcripciones literales fueron codificadas descriptivamente y luego se generaron categorías amplias. Este procedimiento se realizó en un principio por tres investigadores y finalmente un cuarto investigador trianguló la información. Resultados: Emergen cinco dimensiones (accesibilidad, servicios, relación, localización e identidad) compuestas por diferentes temas valorados desde las expectativas y experiencias de los usuarios. La dimensión «identidad» otorga un elemento distintivo respecto a la vinculación con el programa. Conclusión: En general, los usuarios valoran positivamente el programa REDAN. Respecto a la vinculación, describen aspectos facilitadores y otros deficitarios que pueden suponer barreras, frente a las cuales realizan sugerencias. Aspectos como la convivencia entre los usuarios del programa REDAN y los pacientes en tratamiento orientado a la abstinencia generan ambivalencia, pero se identifica que la gestión por parte del equipo minimiza estas dificultades.Objectives: We analyzed the perspective of users enrolled in a harm reduction program that provides syringe exchange, an educational room for «warmth and coffee», a methadone maintenance program, a room for supervised drug consumption, a place for personal hygiene, and medical and psychosocial follow-up. The particularity of this program lies in its integration within an outpatient drug treatment center forming part of a general hospital. Methods: We performed a descriptive study using qualitative methods. Theoretical sampling was conducted. Twelve in-depth interviews and one focus group composed of eight users were carried out. Information analysis was based on grounded theory. Literal transcriptions were coded and subsequently sorted into broad categories. Three researchers participated in this process and finally a fourth researcher triangulated the results. Results: Five dimensions were identified in the users´ discourse: accessibility, service, relationship, localization, and identity. Each consisted of several topics that were evaluated based on the participants´ experiences and expectations. The dimension of identity emerged as a distinctive element in patient-program bonding. Conclusions: The users´ overall evaluation of the program was positive. Facilitators and barriers influencing patient-program bonding were identified and participants suggested ways to remove barriers. The coexistence among users of the harm reduction program and patients treated conventionally provoked ambivalence but the team's management was deemed helpful in easing the difficulties arising from this situation.

Hematopoietic stem cell transplantation (HSCT) for severe ADs was developed over the past 25years and is now validated by national and international medical societies for severe early systemic sclerosis (SSc) and relapsing-remitting multiple sclerosis (MS) and available as part of routine care in accredited center. HSCT is also recommended, with varying levels of evidence, as an alternative treatment for several ADs, when refractory to conventional therapy, including specific cases of connective tissue diseases or vasculitis, inflammatory neurological diseases, and more rarely severe refractory Crohn's disease. The aim of this document was to provide guidelines for the current indications, procedures and follow-up of HSCT in ADs. Patient safety considerations are central to guidance on patient selection and conditioning, always validated at the national MATHEC multidisciplinary team meeting (MDTM) based on recent (less than 3months) thorough patient evaluation. HSCT procedural aspects and follow-up are then carried out within appropriately experienced and Joint Accreditation Committee of International Society for Cellular Therapy and SFGM-TC accredited centres in close collaboration with the ADs specialist. These French recommendations were performed according to HAS/FAI2R standard operating procedures and coordinated by the Île-de-France MATHEC Reference Centre for Rare Systemic Autoimmune Diseases (CRMR MATHEC) within the Filière FAI2R and in association with the Filière MaRIH. The task force consisted of 3 patients and 64 clinical experts from various specialties and French centres. These data-derived and consensus-derived recommendations will help clinicians to propose HSCT for their severe ADs patients in an evidence-based way. These recommendations also give directions for future clinical research in this area. These recommendations will be updated according to newly emerging data. Of note, other cell therapies that have not yet been approved for clinical practice or are the subject of ongoing clinical research will not be addressed in this document., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a dysimmune neuropathy with sensory and/or motor symptoms due to destruction of the myelin sheat secondary to an auto-immune attack. A quarter to a third of patients do not respond to immunomodulatory first line recommended therapies. No second line treatment has shown its effectiveness with a sufficient level of evidence. Autologous hematopoietic stem cell transplantation (AHSCT) is a promising therapy for autoimmune disease, especially for CIDP in recent works. We present in this article an update on the diagnosis of CIDP, its conventional treatments as well as the results of AHSCT in this indication, which was the subject of French recommendations under the aegis of the SFGMTC and neuromuscular disease french faculty (FILNEMUS) as a third line therapy after failure of two first-line and one second-line treatments., (Copyright © 2021 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

The facile reaction of a readily available aminopolyol from the chiral pool, N-methyl-d-glucamine, which avoids the side reactions usually associated to anomers of amino sugars, with epoxide and polyepoxide derivatives, enables the preparation of new non-ionic surfactant-like structures combining hydrophilic and hydrophobic moieties. The molecular architectures thus obtained range from linear to tripodal and pyramidal structures. The resulting substances containing multiple chiral centers exist as diastereomeric mixtures, for which various conformations are likewise possible by virtue of inter-chain interactions. The stability and chirality preferences of all possible stereoisomers have been evaluated in detail by DFT methods. Given the amphiphilic structure of both protected and O-protected derivatives obtained by acetylation, self-aggregation could eventually lead to solvent entrapment. Unfortunately, only one compound behaves as efficient hydrogelator and DMSO-gelator at low concentrations. The issue is also discussed in terms of the different molecular arrangements., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

ANXA11 mutations have previously been discovered in amyotrophic lateral sclerosis (ALS) motor neuron disease. To confirm the contribution of ANXA11 mutations to ALS, a large exome data set obtained from 330 French patients, including 150 familial ALS index cases and 180 sporadic ALS cases, was analyzed, leading to the identification of 3 rare ANXA11 variants in 5 patients. The novel p.L254V variant was associated with early onset sporadic ALS. The novel p.D40Y mutation and the p.G38R variant concerned patients with predominant pyramidal tract involvement and cognitive decline. Neuropathologic findings in a p.G38R carrier associated the presence of ALS typical inclusions within the spinal cord, massive degeneration of the lateral tracts, and type A frontotemporal lobar degeneration. This mutant form of annexin A11 accumulated in various brain regions and in spinal cord motor neurons, although its stability was decreased in patients' lymphoblasts. Because most ANXA11 inclusions were not colocalized with transactive response DNA-binding protein 43 or p62 deposits, ANXA11 aggregation does not seem mandatory to trigger neurodegeneration with additional participants/partner proteins that could intervene., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Motor unit number index (MUNIX) is proposed to monitor neuromuscular disorders. Our objective is to determine the intra-individual variability over time of the MUNIX., Methods: In 11 different hospital centres, MUNIX was assessed twice, at least 3 months apart (range 90-360 days), in tibialis anterior (TA), abductor pollicis brevis (APB), abductor digiti minimi (ADM) and deltoid muscles in 118 healthy subjects. MUNIX sum score 2, 3 and 4 were respectively the sum of the MUNIX of the TA and ADM, of the TA, APB and ADM and of the TA, APB, ADM and deltoid muscles., Results: The repeatability of the MUNIX was better for sum scores than for single muscle recordings. The variability of the MUNIX was independent of sex, age, interval between measurements and was lower for experienced than non-experienced operators. The 95th percentile of the coefficient of variability of the MUNIX sum score 2, 3 and 4 were respectively 22%, 18% and 15% for experienced operators., Conclusions: The MUNIX technique must be performed by experienced operators on several muscles to reduce its variability and improve its reliability., Significance: A variation of the MUNIX sum score ≥20% can be interpreted as a significant change of muscle innervation., Competing Interests: Declaration of Competing Interest Authors don’t have potential conflicts of interest to be disclosed., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The mutarotation equilibrium, by which reducing carbohydrates exist in solution as the α and β anomers of cyclic (furanoid and pyranoid) structures, along with open-chain (aldehyde and hydrate) forms, and whose ratios are depending on factors such as temperature, pH and solvent, portraits a phenomenon involved in numerous processes of chemical and biological importance. Herein, we have developed a DFT-based rationale that provides a broader landscape for anomerizations and ring-open chain interconversions, together with the pivotal role exerted not only by the aldehyde intermediate (essentially the only acyclic structure taken into account so far), but also the hydrate form (often more abundant at the equilibrium). These calculations reveal a more complex and richer scenario than was thought, and identify different mutarotation mechanisms that hinge on every monosaccharide. It is noteworthy that pyranose-furanose interconversion may actually occur without the intermediacy of open-chain forms. For the aldoses evaluated, namely d-glucose, d-ribose, and d-xylose, all structures involved in mutarotation undergo interconversion pathways, whose energy barriers calculated at the M06-2X/6-311++G(d,p) level, are in good agreement with previous experimental measurements., 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 © 2020 Elsevier Ltd. All rights reserved.)

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a chronic autoimmune disease involving the peripheral nervous system, characterized by focal and segmental demyelination accounting for neurological deficit. CIDP diagnosis is based on several criteria and requires the presence of specific clinical symptoms and of demyelinating criteria on the electroneuromyogram (ENMG) or of additional supportive criteria (spinal fluid examination with dissociation between albumin level and cellular abnormalities, nervous abnormalities on MRI or other minor abnormalities on ENMG, demyelinating features on nerve biopsy or patient improvement under so-called first-line therapy with immunodulator treatment). After failure of two successive first line immunomodulating drug therapies (corticosteroids, immunomodulating immunoglobulins, or plasma exchange), several options can be considered as second line therapies. The efficacy of autologous hematopoietic cell transplantation (AHCT) has been shown in CIDP patients. The aim of these recommendations established by a working group of experts from the "Société française de greffe de moelle osseuse et thérapie cellulaire (SFGM-TC)", the group "maladies auto-immunes et thérapie cellulaire (MATHEC)" and the "filière de santé maladies rares neuromusculaire (FILNEMUS)" is to specify the eligibility criteria for AHCT in CIPD patients, to describe the mobilization and the conditioning regimen for the AHCT procedure, as well as the patient standardized post-transplant follow-up and the management of neurological treatment throughout the all procedure., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The autosomal recessive demyelinating form of Charcot-Marie-Tooth can be due to SH3TC2 gene pathogenic variants (CMT4C, AR-CMTde-SH3TC2). We report on a series of 13 patients with AR-CMTde-SH3TC2 among a French cohort of 350 patients suffering from all type of inheritance peripheral neuropathy. The SH3TC2 gene appeared to be the most frequently mutated gene for demyelinating neuropathy in this series by NGS. Four new pathogenic variants have been identified: two nonsense variants (p.(Tyr970*), p.(Trp1199*)) and two missense variants (p.(Leu1126Pro), p.(Ala1206Asp)). The recurrent variant p.Arg954* was present in 62%, and seems to be a founder mutation. The phenotype is fairly homogeneous, as all these patients, except the youngest ones, presented scoliosis and/or hearing loss., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The aim of this work is to investigate a novel cork wastewater (CW) purification method that combines flocculation/adsorption with the microwave assisted regeneration of coconut powder activated carbon (CPAC). The flocculation treatment made use of FeSO 4 ·7H 2 O/NaOH and provided high removal efficiency, as shown by the observed values of UV 254 (90%), chemical oxygen demand (COD, 86%), polyphenols (PP, 81%),total solid (TS, 40%), total suspended solid (TSS, 62%), and total dissolved solid (TDS, 18%). After the flocculation and filtration, CPAC was used to further remove left TSS, TDS and dissolved organics. The effects of CPAC amount, pH value and adsorption time have been studied. It was found that 250 mg is the optimum CPAC amount for the treatment of 50 mL CW at pH 3.5 for 10 min. Overall process effectiveness can be summarised as follows: UV 254 (100%), COD (98%), PP (100%), TS (58%), TSS (93%), and TDS (24%), while the characteristic colour of the CW completely disappeared. The microwave regenerated CPAC can undergo five runs without appreciable losses in removal efficiency. Predictably, this simple and scalable process could afford a promising treatment method for other industrial wastewaters with high content of organic matters such as PP, phenolic acids and tannins., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Myopathies and muscular dystrophies (M-MDs) are genetically heterogeneous diseases, with >100 identified genes, including the giant and complex titin (TTN) and nebulin (NEB) genes. Next-generation sequencing technology revolutionized M-MD diagnosis and revealed high frequency of TTN and NEB variants. We developed a next-generation sequencing diagnostic strategy targeted to the coding sequences of 135 M-MD genes. Comparison of two targeted capture technologies (SeqCap EZ Choice library capture kit and Nextera Rapid Capture Custom Enrichment kit) and of two whole-exome sequencing kits (SureSelect V5 and TruSeq RapidExome capture) revealed best coverage with the SeqCap EZ Choice protocol. A marked decrease in coverage was observed with the other kits, affecting mostly the first exons of genes and the repeated regions of TTN and NEB. Bioinformatics analysis strategy was fine-tuned to achieve optimal detection of variants, including small insertions/deletions (INDELs) and copy number variants (CNVs). Analysis of a cohort of 128 patients allowed the detection of 52 substitutions, 13 INDELs (including a trinucleotide repeat expansion), and 3 CNVs. Two INDELs were localized in the repeated regions of NEB, suggesting that these mutations may be frequent but underestimated. A large deletion was also identified in TTN that is, to our knowledge, the first published CNV in this gene., (Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Hepatitis E virus (HEV) has been associated with a number of neurological syndromes, but causality has not yet been established. The aim of this study was to explore the relationship between HEV and neurological illness by prospective HEV testing of patients presenting with acute non-traumatic neurological injury., Methods: Four hundred and sixty-four consecutive patients presenting to hospital with acute non-traumatic neurological illnesses were tested for HEV by serology and PCR from four centres in the UK, France and the Netherlands., Results: Eleven of 464 patients (2.4%) had evidence of current/recent HEV infection. Seven had HEV RNA identified in serum and four were diagnosed serologically. Neurological cases in which HEV infection was found included neuralgic amyotrophy (n=3, all PCR positive); cerebral ischemia or infarction (n=4); seizure (n=2); encephalitis (n=1); and an acute combined facial and vestibular neuropathy (n=1). None of these cases were clinically jaundiced and median ALT at presentation was 24IU/L (range 8-145). Cases of HEV-associated neuralgic amyotrophy were found in each of the participating countries: all were middle-aged males with bilateral involvement of the brachial plexus., Conclusions: In this cohort of patients with non-traumatic neurological injury, 2.4% had evidence of HEV infection. Symptoms of hepatitis were mild or absent and no patients were jaundiced. The cases of HEV-associated neuralgic amyotrophy had similarities with other HEV-associated cases described in a large retrospective study. This observation supports a causal relationship between HEV and neuralgic amyotrophy. To further understand the relevance of HEV infection in patients with acute neurological illnesses, case-control studies are warranted. Lay summary: Hepatitis E virus (HEV), as its name suggests, is a hepatotropic virus, i.e. it causes damage to the liver (hepatitis). Our findings show that HEV can also be associated with a range of injury to the nervous system., (Copyright © 2017 European Association for the Study of the Liver. All rights reserved.)

Background: Both type 1 myotonic dystrophy (MD1) and Brugada syndrome (BrS) may be complicated by conduction disturbances and sudden death. Spontaneous BrS has been observed in MD1 patients, but the prevalence of drug-induced BrS in MD1 is unknown., Objective: The purpose of this study was to prospectively assess the prevalence of type 1 ST elevation as elicited during pharmacologic challenge with Class 1C drugs in a subgroup of MD1 patients and to further establish correlations with ECG and electrophysiologic variables and prognosis., Methods: From a group of unselected 270 MD1 patients, ajmaline or flecainide drug challenge was performed in a subgroup of 44 patients (27 men, median age 43 years) with minor depolarization/repolarization abnormalities suggestive of possible BrS. The presence of type 1 ST elevation after drug challenge was correlated to clinical, ECG, and electrophysiologic variables., Results: Eight of 44 patients (18%) presented with BrS after drug challenge. BrS was seen more often in men (26% vs 6%, P = .09) and was related to younger age (35 vs 48 years, P = .07). BrS was not correlated to symptoms, baseline ECG, HV interval, results of signal-averaged ECG, or abnormalities on ambulatory recordings. MD1 patients with BrS had longer corrected QT intervals, greater increase in PR interval after drug challenge, and higher rate of inducible ventricular arrhythmias (62% vs 21%, P = .03). Twelve patients were implanted with a pacemaker and 5 with an implantable cardioverter-defibrillator. Significant bradycardia did not occur in any patients, and malignant ventricular arrhythmia never occurred during median 7-year follow-up (except 1 hypokalemia-related ventricular fibrillation)., Conclusion: BrS is elicited by a Class 1 drug in 18% of MD1 patients presenting with minor depolarization/repolarization abnormalities at baseline, but the finding seems to be devoid of a prognostic role., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Chediak-Higashi syndrome is a rare autosomal recessive disease characterized by partial oculocutaneous albinism, recurrent pyogenic infections and the presence of giant granules in many cells such as leucocytes (hallmark of the disease). Neurological symptoms are rare. We describe two sisters who presented the same phenotype of slowly progressive motor neuronopathy (with Babinski sign in one patient); biopsy of the sural nerve showed an abnormal endoneurial accumulation of lipofuscin granules. We discuss these two observations and compare them with the few case reports of neuropathy in Chediak-Higashi syndrome., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Formation of thin films on titanium alloys incorporating bioactive small molecules or macromolecules is a route to improve their biocompatibility. Aminoalkylsilanes are commonly employed as interface reagents that combine good adhesion properties with an amino tail group susceptible of further functionalization. This article introduces a reproducible methodology to obtain a cross-linked polymer-type brush structure of covalently-bonded aminoalkylsiloxane chains on Ti6Al4V. The experimental protocol can be fine-tuned to provide a high density of surface-coated amino groups (threshold value: 2.1±0.1×10(-8) mol cm(-2)) as proven by chemical and spectrophotometric analyses. Using a model reaction involving the condensation of 3-aminopropyltrimethoxysilane (APTMS) on Ti6Al4V alloy, we herein show the effects of reaction temperature, reaction time and solvent humidity on the composition and structure of the film. The stability of the resulting coating under physiological-like conditions as well as the possibility of surface re-silanization has also been evaluated. To verify if detrimental effects on the biological performance of the Ti6Al4V alloy were induced by this coverage, human primary osteoblasts behavior, Staphylococci adhesion and biofilm formation have been tested and compared to the Ti6Al4V oxidized surface. Reaction with trans-cinnamaldehyde has used in order to determine useful amino groups at aminosilanized surface, XPS and UV analyses of imino derivatives generated reveal that almost a 50% of these groups are actually available at the siloxane chains., (Copyright © 2013 Elsevier B.V. All rights reserved.)

It has been shown that hepatitis E virus (HEV) may be responsible for chronic hepatitis in solid-organ transplant patients. It has also been suggested that HEV may be responsible for atypical neurological symptoms during the acute phase. However, the relationship between the neurological symptoms and HEV infection was based on the detection of anti-HEV IgM in the sera. Herein, we report a case where neurological symptoms, that is peripheral nerve involvement with proximal muscular weakness that affected the four limbs joints with central nervous-system involvement and bilateral pyramidal syndrome, occurred in a kidney-transplant patient who was chronically infected by HEV. For the first time, HEV RNA was detected in the serum and cerebrospinal fluid. In addition, clonal HEV sequences were analyzed in both compartments, that is serum and cerebrospinal fluid. The discovery of quasispecies compartmentalization and its temporal association suggests that neurological symptoms could be linked to the emergence of neurotropic variants.

Despite the comprehensive literature and enormous versatility of chiral imines derived from aminosugars and aldehydes, the corresponding counterparts generated from ketones remain an underestimated research subject. Filling in the gap, this manuscript sheds light on the synthetic and structural aspects of such substances and updates the few antecedents reported so far., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background: Microbubbles used for echo-contrast agents accelerate enzymatic fibrinolysis of clots exposed to low-frequency ultrasound (US). It is not known whether microbubbles are also effective in enhancing high-frequency US-driven enzymatic fibrinolysis., Methods and Results: Calibrated whole blood clots were exposed to US, or US and galactose-based microbubbles (Levovist), with or without recombinant tissue plasminogen activator (rt-PA) in an in-vitro flow system. We used low-intensity, 2-MHz, pulsed wave US. Relative weight reduction of clot +/- SD was 30.7 +/- 9.5% after exposure to microbubbles, rt-PA and US, 13.1 +/- 2.6% after exposure to rt-PA and US, 10.9 +/- 3.6% after exposure to microbubbles and US, and 6.1 +/- 1.9% after exposure to US alone. anova demonstrated a significant effect of rt-PA (P =0.001), microbubbles (P = 0.012), and interaction of both (P = 0.022)., Conclusions: The application of galactose-based microbubbles (Levovist) strongly accelerates lysis of clots exposed to 2 MHz, low-intensity US in vitro both with and without rt-PA. The findings suggest a synergy between microbubbles and rt-PA. These methods routinely used for transcranial diagnostic applications have the potential to improve the efficacy of intravenous rt-PA in acute ischemic stroke.