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Background and Aims: Baseline cardiovascular toxicity risk stratification is critical in cardio-oncology. The Heart Failure Association (HFA) and International Cardio-Oncology Society (ICOS) score aims to assess this risk but lacks real-life validation. This study validates the HFA-ICOS score for anthracycline-induced cardiovascular toxicity., Methods: Anthracycline-treated patients in the CARDIOTOX registry (NCT02039622) were stratified by the HFA-ICOS score. The primary endpoint was symptomatic or moderate to severe asymptomatic cancer therapy-related cardiac dysfunction (CTRCD), with all-cause mortality and cardiovascular mortality as secondary endpoints., Results: The analysis included 1066 patients (mean age 54 ± 14 years; 81.9% women; 24.5% ≥65 years). According to the HFA-ICOS criteria, 571 patients (53.6%) were classified as low risk, 333 (31.2%) as moderate risk, 152 (14.3%) as high risk, and 10 (0.9%) as very high risk. Median follow-up was 54.8 months (interquartile range 24.6-81.8). A total of 197 patients (18.4%) died, and 718 (67.3%) developed CTRCD (symptomatic: n = 45; moderate to severe asymptomatic: n = 24; and mild asymptomatic: n = 649). Incidence rates of symptomatic or moderate to severe symptomatic CTRCD and all-cause mortality significantly increased with HFA-ICOS score [hazard ratio 28.74, 95% confidence interval (CI) 9.33-88.5; P < .001, and hazard ratio 7.43, 95% CI 3.21-17.2; P < .001) for very high-risk patients. The predictive model demonstrated good calibration (Brier score 0.04, 95% CI 0.03-0.05) and discrimination (area under the curve 0.78, 95% CI 0.70-0.82; Uno's C-statistic 0.78, 95% CI 0.71-0.84) for predicting symptomatic or severe/moderate asymptomatic CTRCD at 12 months., Conclusions: The HFA-ICOS score effectively categorizes patients by cardiovascular toxicity risk and demonstrates strong predictive ability for high-risk anthracycline-related cardiovascular toxicity and all-cause mortality., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The aim of this study was to describe a very rare presentation of ependymoma that can derive from intraoperative complications for surgeons and increased morbidity for the patients. Multiple cases of mobile cauda equina tumors leading to inadequate approach have been reported in the literature, however, the reports of ependymoma histology are very rare. This report describes the third adult case in recent years and a retrospective review of cases reported in the literature until today. We show the clinical and radiographic presentation of a 79 years old patient that presented a mobile cauda equina tumor in the preoperative image, who went to surgery for resection and arthrodesis, obtaining in post-operative histology the diagnostic of ependymoma. The preoperative image shows the migration of the tumor avoiding the wrong approach. The patient went to surgery for laminectomy, pedicular screw arthrodesis L1-S1, and tumor removal, obtaining a complete resection and confirmed histology diagnostic of ependymoma, unfortunately, the patient died five days after by a cardiac arrest. The recent literature reports only four cases of mobile ependymoma, two of them in pediatrics patients and just only two adult cases, which means this is the third adult case of an ependymoma. Mobile cauda equina ependymoma is a very rare neoplasm presentation but is an entity that can lead to mistakes in the approach and may be useful for the neurosurgeons who day per day treat this pathology beware of this possibility.

Lingering cardiac symptoms are increasingly recognised complications of severe acute respiratory syndrome coronavirus 2 infection, now referred to as post-acute cardiovascular sequelae of COVID-19 (PASC). In the acute phase, cardiac injury is driven by cytokine release and stems from ischaemic and thrombotic complications, resulting in myocardial necrosis. Patients with pre-existing cardiac conditions are particularly vulnerable. Myocarditis due to a direct viral infection is rare. Chronic symptoms relate to either worsening of pre-existing heart disease (PASC - cardiovascular disease) or delayed chronic inflammatory condition due to heterogenous immune dysregulation (PASC - cardiovascular syndrome), the latter affecting a broad segment of previously well people. Both PASC presentations are associated with increased cardiovascular risk, long-term disability and reduced quality of life. The recognition and management of PASC in clinical settings remains a considerable challenge. Sensitive diagnostic methods are needed to detect subtler inflammatory changes that underlie the persistent symptoms in PASC - cardiovascular syndrome, alongside considerable clinical experience in inflammatory cardiac conditions., Competing Interests: Disclosure: VOP and EN have received speaker fees from Bayer and Siemens, and scientific grants from Bayer. All other authors have no conflicts of interest to declare., (Copyright © The Author(s), 2023. Published by Radcliffe Group Ltd.)

An 86-year-old patient with non-valvular atrial fibrillation was referred to our institution to undergo a left atrial appendage (LAA) closure for recurrent gastrointestinal bleeding on direct oral anticoagulants. The transesophageal echocardiogram (TEE) performed the previous day evaluated the morphology and dimensions of the LAA and ruled out any thrombus. During the procedure, a pigtail catheter was inserted into the LAA, observing an unusual image we describe as a culde- sac, without an anomalous connection with any drainage in other vessel or cavity. After additional imaging studies, we concluded that it was morphology related to LAA, which we have termed the "water-gun" morphology. Four morphologies have been described based on the shape of the central and secondary lobes. To the best of our knowledge, this is the first description of a fifth type, which was shown to be effectively closed with current closure devices.

The molecular mechanisms underlying circuit re-wiring in the mature brain remains ill-defined. An eloquent example of adult circuit remodelling is the hippocampal mossy fiber (MF) sprouting found in diseases such as temporal lobe epilepsy. The molecular determinants underlying this retrograde re-wiring remain unclear. This may involve signaling system(s) controlling axon specification/growth during neurodevelopment reactivated during epileptogenesis. Since adenosine A 2A receptors (A 2A R) control axon formation/outgrowth and synapse stabilization during development, we now examined the contribution of A 2A R to MF sprouting. A 2A R blockade significantly attenuated status epilepticus(SE)-induced MF sprouting in a rat pilocarpine model. This involves A 2A R located in dentate granule cells since their knockdown selectively in dentate granule cells reduced MF sprouting, most likely through the ability of A 2A R to induce the formation/outgrowth of abnormal secondary axons found in rat hippocampal neurons. These A 2A R should be activated by extracellular ATP-derived adenosine since a similar prevention/attenuation of SE-induced hippocampal MF sprouting was observed in CD73 knockout mice. These findings demonstrate that A 2A R contribute to epilepsy-related MF sprouting, most likely through the reactivation of the ability of A 2A R to control axon formation/outgrowth observed during neurodevelopment. These results frame the CD73-A 2A R axis as a regulator of circuit remodeling in the mature brain., (© 2022. The Author(s).)

Autism spectrum disorder (ASD) involves genetic and environmental components. The underlying circuit mechanisms are unclear, but behaviorally, aversion toward unfamiliarity, a hallmark of autism, might be involved. Here, we show that in Shank3 ΔC/ΔC ASD model mice, exposure to novel environments lacking familiar features produces long-lasting failure to engage and repetitive behaviors upon re-exposure. Inclusion of familiar features at first context exposure prevented enhanced dopamine transients in tail of striatum (TS) and restored context-specific control of engagement to wild-type levels in Shank3 ΔC/ΔC mice. Engagement upon context re-exposure depended on the activity in prelimbic cortex (PreL)-to-TS projection neurons in wild-type mice and was restored in Shank3 ΔC/ΔC mice by the chemogenetic activation of PreL→TS projection neurons. Environmental enrichment prevented ASD-like phenotypes by obviating the dependence on PreL→TS activity. Therefore, novel context experience has a key role in triggering ASD-like phenotypes in genetically predisposed mice, and behavioral therapies involving familiarity and enrichment might prevent the emergence of ASD phenotypes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cognition and behavior are tightly linked to synaptic function. A growing body of evidence suggests that aberrant neurotransmission, caused by changes in synaptic protein expression levels, may be a major cause underlying different brain disorders. These changes in expression result in abnormal synaptic organization or function, leading to impaired neurotransmission and unbalanced circuit operations. Here, we review the data supporting the involvement of mutations in genes coding for kainate receptor (KAR) subunits in the pathogenesis of psychiatric disorders and Down syndrome (DS). We show that most of these mutations do not affect the biophysical properties or the receptors, but rather alter subunit expression levels. On the basis of reports studying KAR genes mutations in mouse models of autism spectrum disorders and DS, we illustrate how deviations from the physiological regulatory role that these receptors play in neurotransmitter release and plasticity give rise to synaptic alterations that lead to behavioral and cognitive deficits underlying these disorders., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Extensive research over the past decades has characterized multiple forms of synaptic plasticity, identifying them as key processes that allow the brain to operate in a dynamic manner. Within the wide variety of synaptic plasticity modulators, kainate receptors are receiving increasing attention, given their diversity of signaling mechanisms and cellular expression profile. Here, we summarize the experimental evidence about the involvement of kainate receptor signaling in the regulation of short- and long-term plasticity, from the perspective of the regulation of neurotransmitter release. In light of this evidence, we propose that kainate receptors may be considered homeostatic modulators of neurotransmitter release, able to bidirectionally regulate plasticity depending on the functional history of the synapse., Competing Interests: Declaration of Competing Interest Since one of the authors is the Editor of the Journal, we declare that the peer review of this manuscript has been handled independently and that the Editor-in-Chief has not been involved in editorial decisions concerning this paper., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

We report the value of non-linear optical parameters in graphene oxide (GO) using the Z-scan technique. The value of the non-linear refractive index η 2 , non-linear absorption coefficient β and the complex value of third order susceptibility χ (3) in samples with different concentrations of GO diluted in distilled water were determined. The value of these parameters were obtained directly from the measurement of normalized transmittance of each sample as a consequence of its non-linear response when are exposed to electromagnetic radiation from a Nd:YAG laser emitting at 532 nm in CW mode. In addition, we found that the parameters η 2 , β and χ (3) growth by increasing excitation laser power, where β showed an high order of magnitude around ~10 -2 cm/W., 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 B.V. All rights reserved.)

Organic compounds and vegetable origin oils are subject to scratiny in the photonics and nonlinear optics area, due to their high non-linear response: a characteristic linked to the molecular nature of these compounds and their own chemical bond. In the food industry, quick and non-invasive studies are needed to evaluate the nutritional quality of edible products. The nonlinear optical response of 4 vegetable oils was analyzed: extra virgin olive oil (EVOO), extra virgin sesame oil (EVSO), extra refined linseed oil (ERLO) and virgin avocado oil (VAVO), using the Z-scan technique. Where the third order electric susceptibility value (χ 3 ), refractive index (η 2 ) and characteristic non-linear absorption coefficient (β) were determined for each compound. Parameters that were found by measuring the transmittance as a function of the excitation power using a Nd: YAG laser of 532 nm operating in CW mode. In addition, the η 2 response was compared according to the oil type, it was determined that EVOO presents a greater non-linear response at low excitation potencies. Therefore, an additional study was performed on samples exposed to thermal stress to evaluate oxidative stability, again using the Z-scan technique n order to review the relationship between nonlinear optical properties with chemical changes resulting from heating., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Overinhibition is assumed one of the main causes of cognitive deficits (e.g. memory impairment) in mouse models of Down syndrome (DS). Yet the mechanisms that drive such exaggerated synaptic inhibition and their behavioral effects remain unclear. Here we report the existence of bidirectional alterations to the synaptic inhibition on CA1 pyramidal cells in the Ts2Cje mouse model of DS which are associated to impaired spatial memory. Furthermore, we identify triplication of the kainate receptor (KAR) encoding gene Grik1 as the cause of these phenotypes. Normalization of Grik1 dosage in Ts2Cje mice specifically restored spatial memory and reversed the bidirectional alterations to CA1 inhibition, but not the changes in synaptic plasticity or the other behavioral modifications observed. We propose that modified information gating caused by disturbed inhibitory tone rather than generalized overinhibition underlies some of the characteristic cognitive deficits in DS.

The Internet of Things scenario is composed of an amalgamation of physical devices. Those physical devices are heterogeneous in their nature both in terms of communication protocols and in data exchange formats. The Web of Things emerged as a homogenization layer that uses well-established web technologies and semantic web technologies to exchange data. Therefore, the Web of Things enables such physical devices to the web, they become Web Things. Given such a massive number of services and processes that the Internet of Things/Web of Things enables, it has become almost mandatory to describe their properties and characteristics. Several web ontologies and description frameworks are devoted to that purpose. Ontologies such as SOSA/SSN or OWL-S describe the Web Things and their procedures to sense or actuate. For example, OWL-S complements SOSA/SSN in describing the procedures used for sensing/actuating. It is, however, not its scope to be specific enough to enable a computer program to interpret and execute the defined flow of control. In this work, it is our goal to investigate how we can model those procedures using web ontologies in a manner that allows us to directly deploy the procedure implementation. A prototype implementation of the results of our research is implemented along with an analysis of several use cases to show the generality of our proposal.

Cardiovascular disease remains a leading cause of morbidity and mortality globally. Changing natural history of the disease due to improved care of acute conditions and ageing population necessitates new strategies to tackle conditions which have more chronic and indolent course. These include an increased deployment of safe screening methods, life-long surveillance, and monitoring of both disease activity and tailored-treatment, by way of increasingly personalized medical care. Cardiovascular magnetic resonance (CMR) is a non-invasive, ionising radiation-free method, which can support a significant number of clinically relevant measurements and offers new opportunities to advance the state of art of diagnosis, prognosis and treatment. The objective of the SCMR Clinical Trial Taskforce was to summarizes the evidence to emphasize where currently CMR-guided clinical care can indeed translate into meaningful use and efficient deployment of resources results in meaningful and efficient use. The objective of the present initiative was to provide an appraisal of evidence on analytical validation, including the accuracy and precision, and clinical qualification of parameters in disease context, clarifying the strengths and weaknesses of the state of art, as well as the gaps in the current evidence This paper is complementary to the existing position papers on standardized acquisition and post-processing ensuring robustness and transferability for widespread use. Themed imaging-endpoint guidance on trial design to support drug-discovery or change in clinical practice (part II), will be presented in a follow-up paper in due course. As CMR continues to undergo rapid development, regular updates of the present recommendations are foreseen.

Background: The influence of dietary habits on the development of gastric adenocarcinoma is not clear. The objective of the present study was to explore the association of three previously identified dietary patterns with gastric adenocarcinoma by sex, age, cancer site, and morphology., Methods: MCC-Spain is a multicase-control study that included 295 incident cases of gastric adenocarcinoma and 3040 controls. The association of the Western, Prudent, and Mediterranean dietary patterns-derived in another Spanish case-control study-with gastric adenocarcinoma was assessed using multivariable logistic regression models with random province-specific intercepts and considering a possible interaction with sex and age. Risk according to tumor site (cardia, non-cardia) and morphology (intestinal/diffuse) was evaluated using multinomial regression models., Results: A high adherence to the Western pattern increased gastric adenocarcinoma risk [odds ratio fourth&#95;vs.&#95;first&#95;quartile (95% confidence interval), 2.09 (1.31; 3.33)] even at low levels [odds ratio second&#95;vs.&#95;first&#95;quartile (95% confidence interval), 1.63 (1.05; 2.52)]. High adherence to the Mediterranean dietary pattern could prevent gastric adenocarcinoma [odds ratio fourth&#95;vs.&#95;first&#95;quartile (95% confidence interval), 0.53 (0.34; 0.82)]. Although no significant heterogeneity of effects was observed, the harmful effect of the Western pattern was stronger among older participants and for non-cardia adenocarcinomas, whereas the protective effect of the Mediterranean pattern was only observed among younger participants and for non-cardia tumors., Conclusion: Decreasing the consumption of fatty and sugary products and of red and processed meat in favor of an increase in the intake of fruits, vegetables, legumes, olive oil, nuts, and fish might prevent gastric adenocarcinoma.

Background: Coronary artery disease (CAD) remains the major cause of cardiac morbidity and mortality worldwide, despite the advances in treatment with coronary revascularization and modern antiremodeling therapy. Risk stratification in CAD patients is primarily based on left ventricular volumes, ejection fraction (LVEF), risk scores, and the presence and extent of late gadolinium enhancement (LGE). The prognostic role of T1 mapping in noninfarcted myocardium in CAD patients has not yet been determined., Objectives: This study sought to examine prognostic significance of native T1 mapping of noninfarcted myocardium in patients with CAD., Methods: A prospective, observational, multicenter longitudinal study of consecutive patients undergoing routine cardiac magnetic resonance imaging with T1 mapping and LGE. The primary endpoint was all-cause mortality. Major adverse cardiocerebrovascular events (MACCE) (cardiac mortality, nonfatal acute coronary syndrome, stroke, and appropriate device discharge) are also reported., Results: A total of 34 deaths and 71 MACCE (n = 665, males n = 424, median age [interquartile range] 57 [22] years; 64%; median follow-up period of 17 [11] months) were observed. Native T1 and extracellular volume were univariate predictors of outcome. Native T1 and LGE were stronger predictors of survival and MACCE compared with extracellular volume, LVEF, cardiac volumes, and clinical scores (p < 0.001). Native T1 of noninfarcted myocardium was the sole independent predictor of all-cause mortality (chi-square = 21.7; p < 0.001), which was accentuated in the absence of LGE or LVEF ≤35%. For MACCE, native T1 and LGE extent were joint independent predictors (chi-square = 25.6; p < 0.001)., Conclusions: Characterization of noninfarcted myocardium by native T1 is an important predictor of outcome in CAD patients, over and above the traditional risk stratifiers. The current study's results provide a basis for a novel risk stratification model in CAD based on a complementary assessment of noninfarcted myocardium and post-infarction scar, by native T1 mapping and LGE, respectively., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Neurotransmitter receptors are responsible for the transfer of information across the synapse. While ionotropic receptors form ion channels and mediate rapid membrane depolarization, so-called metabotropic receptors exert their action though slower, less direct intracellular signaling pathways. Glutamate, GABA, and acetylcholine can activate both ionotropic and metabotropic receptors, yet the distinction between these "canonical" signaling systems has become less clear since ionotropic receptors were proposed to also activate second messenger systems, defining a "non-canonical" signaling pathway. How these alternative pathways affect neuronal circuit activity is not well understood, and their influence could be more significant than previously anticipated. In this review, we examine the evidence available that supports the existence of parallel and unsuspected signaling pathways used by ionotropic neurotransmitter receptors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: Left ventricular (LV) transient ischemic dilatation (TID) is not clear how it relates to inducible myocardial ischemia during stress echocardiography (SE)., Methods and Results: Eighty-eight SEs were examined from the site certification phase of the ISCHEMIA Trial. LV end-diastolic volume (EDV) and end-systolic volume (ESV) were measured at rest and peak stages and the percent change calculated. Moderate or greater ischemia was defined as ≥3 segments with stress-induced severe hypokinesis or akinesis. Optimum cut points in stress-induced percent EDV and ESV change that identified moderate or greater myocardial ischemia were analyzed. Analysis from percentage distribution identified a > 13% LV volume increase in EDV or a > 9% LV volume increase in ESV as the optimum cutoff points for moderate or greater ischemia. Using these definitions for TID, there were 27 (31%) with TIDESV and 12 (14%) with TIDEDV . By logistic regression analysis and receiver operating characteristic curves, the percent change in ESV had a stronger association with moderate or greater myocardial ischemia than that of EDV change. Compared to those without TIDESV , cases with TIDESV had larger extent of inducible wall-motion abnormalities, lower peak stress LVEF, and higher likelihood of moderate or grater ischemia. For moderate or greater myocardial ischemia detection, TIDESV had a sensitivity of 46%, specificity of 83%, positive predictive value of 70%, and negative predictive value of 64%., Conclusion: Transient ischemic dilatation by SE is a marker of extensive myocardial ischemia and can be used as an additional marker of higher risk., (© 2016, Wiley Periodicals, Inc.)

Light-regulated drugs allow remotely photoswitching biological activity and enable plausible therapies based on small molecules. However, only freely diffusible photochromic ligands have been shown to work directly in endogenous receptors and methods for covalent attachment depend on genetic manipulation. Here we introduce a chemical strategy to covalently conjugate and photoswitch the activity of endogenous proteins and demonstrate its application to the kainate receptor channel GluK1. The approach is based on photoswitchable ligands containing a short-lived, highly reactive anchoring group that is targeted at the protein of interest by ligand affinity. These targeted covalent photoswitches (TCPs) constitute a new class of light-regulated drugs and act as prosthetic molecules that photocontrol the activity of GluK1-expressing neurons, and restore photoresponses in degenerated retina. The modularity of TCPs enables the application to different ligands and opens the way to new therapeutic opportunities.

Obstetric brachial plexus injuries (OBPP) are a relatively common stretch injury of the brachial plexus that occurs during delivery. Roughly 30 % of patients will not recover completely and will need a surgical repair. Two main treatment strategies have been used: primary surgery, consisting in exploring and reconstructing the affected portions of the brachial plexus within the first few months of the patient's life, and secondary procedures that include tendon or muscle transfers, osteotomies, and other orthopedic techniques. Secondary procedures can be done as the only surgical treatment of OBPP or after primary surgery, in order to minimize any residual deficits. Two things are crucial to achieving a good outcome: (1) the appropriate selection of patients, to separate those who will spontaneously recover from those who will recover only partially or not at all; and (2) a good surgical technique. The objective of the present review is to assess the published literature concerning certain controversial issues in OBPP, especially in terms of the true current state of primary and secondary procedures, their results, and the respective roles each plays in modern-day treatment of this complex pathology. Considerable published evidence compiled over decades of surgical experience favors primary nerve surgery as the initial therapeutic step in patients who do not recover spontaneously, followed by secondary surgeries for further functional improvement. As described in this review, the results of such treatment can greatly ameliorate function in affected limbs. For best results, multi-disciplinary teams should treat these patients.

Kainate receptors (KARs) are found ubiquitously in the CNS and are present presynaptically and postsynaptically regulating synaptic transmission and excitability. Functional studies have proven that KARs act as ion channels as well as potentially activating G-proteins, thus indicating the existance of a dual signaling system for KARs. Nevertheless, it is not clear how these ion channels activate G-proteins and which of the KAR subunits is involved. Here we performed a proteomic analysis to define proteins that interact with the C-terminal domain of GluK1 and we identified a variety of proteins with many different functions, including a Go α subunit. These interactions were verified through distinct in vitro and in vivo assays, and the activation of the Go protein by GluK1 was validated in bioluminescence resonance energy transfer experiments, while the specificity of this association was confirmed in GluK1-deficient mice. These data reveal components of the KAR interactome, and they show that GluK1 and Go proteins are natural partners, accounting for the metabotropic effects of KARs., (Copyright © 2015 the authors 0270-6474/15/355171-09$15.00/0.)

The palmar triangle is an area vascularized by perforator arteries arising from the common digital palmar arteries. The aim of this article was to perform an anatomical study of common digital palmar arteries perforators. Twelve injected specimens were included in this study. The purpose was to quantify the number of perforator arteries of each common digital palmar arteries in the 2nd, 3rd, and 4th intermetacarpal space, measure distances between them, between the distal perforator and corresponding commissure, and the distance between the proximal perforator and the superficial palmar arch. Four to eight perforators were arising from common digital palmar arteries of the 2nd, 3rd, and 4th intermetacarpal space. The average distance between perforator arteries was 6.5 mm, between superficial palmar arch and proximal perforator artery - 8.2 mm, between the distal perforator artery and corresponding commissure - 6.3 mm., (© The Author(s) 2014.)

We reviewed late functional results of a modified Steindler procedure in patients with obstetrical brachial plexus palsy and poor active elbow flexion. From 1982 to 2005, we reviewed final functional results and complications of 27 cases with flexion weakness of the elbow secondary to obstetrical brachial plexus injury, treated with a modified Steindler procedure. At the end of the follow-up, the mean active elbow flexion was 97° and the mean extensor lag was 10°. In the long-term follow-up, the modified Steindler procedure maintained good results in 67% of the cases in our series, and this percentage raised by 82% when the wrist extensor was present or restored before the Steindler procedure. There were poor results in 19% of the patients, but no major complications., (© The Author(s) 2014.)

The CRMP2 and CRMP4 proteins are strongly expressed in the developing nervous system, mediating neurite outgrowth, neuronal polarity, and axon guidance. In the present study, we demonstrate the interaction of the CRMP2 and CRMP4 proteins with the GluK5 subunit of the kainate (KA) receptor (KAR) and investigated the role of KARs in modulating the development of cultured mouse DRG neurons. We found that KARs modulate neuronal maturation and neurite outgrowth in a bidirectional manner. Accordingly, low concentrations of KA delayed maturation and enhanced neurite outgrowth, whereas maturation was promoted by higher concentrations of KA that attenuated neuritic elongation. The effects of weak KAR activation were prevented by blocking their noncanonical signaling and involved a differential regulation of CRMP2. Whereas the delay in maturation involves PKC-mediated phosphorylation of CRMP2 at T555 leading to a downregulation of membrane Cav2.2, the promotion of neurite outgrowth is achieved by dephosphorylation at T514 at the growth cones, the latter reflecting PKC-driven enhancement of GSK3β phosphorylation at S9. Together, these findings indicate that noncanonical KAR signaling influences neuronal development by modulating CRMP2 activity.

In commercial dairy production, the risk of drug residues and environmental pollutants in milk from ruminants has become an outstanding problem. One of the main determinants of active drug secretion into milk is the ATP-binding cassette transporter G2/breast cancer resistance protein (ABCG2/BCRP). It is located in several organs associated with drug absorption, metabolism, and excretion, and its expression is highly induced during lactation in the mammary gland of ruminants, mice, and humans. As a consequence, potential contamination of milk could expose suckling infants to xenotoxins. In cows, a SNP for this protein affecting quality and quantity of milk production has been described previously (Y581S). In this study, our main purpose was to determine whether this polymorphism has an effect on transcellular transport of veterinary drugs because this could alter substrate pharmacokinetics and milk residues. We stably expressed the wild-type bovine ABCG2 and the Y581S variant in Madin-Darby canine kidney epithelial cells (MDCKII) and MEF3.8 cell lines generating cell models in which the functionality of the bovine transporter could be addressed. Functional studies confirmed the greater functional activity in mitoxantrone accumulation assays for the Y581S variant with a greater relative V(MAX) value (P = 0.040) and showed for the first time that the Y581S variant presents greater transcellular transport of the model ABCG2 substrate nitrofurantoin (P = 0.024) and of 3 veterinary antibiotics, the fluoroquinolone agents enrofloxacin (P = 0.035), danofloxacin (P = 0.001), and difloxacin (P = 0.008), identified as new substrates of the bovine ABCG2. In addition, the inhibitory effect of the macrocyclic lactone ivermectin on the activity of wild-type bovine ABCG2 and the Y581S variant was also confirmed, showing a greater inhibitory potency on the wild-type protein at all the concentrations tested (5 μM, P = 0.017; 10 μM, P = 0.001; 25 μM, P = 0.008; and 50 μM, P = 0.003). Differential transport activity depending on the genotype together with the differential inhibition pattern might have clinical consequences, including changes in substrate pharmacokinetics (and subsequently pharmacodynamics) and more specifically, changes in secretion of ABCG2 substrates into milk, potentially implying important consequences to veterinary therapeutics.

The aim of this study was to evaluate, through a retrospective and external study, the quality of Spanish hand hygiene guidelines and protocols. None of the guidelines achieved a score of 100% in all areas. The mean score was only 43.9%, ranging from 23.8% for rigorous design to 69.4% for clarity and presentation. None of the protocols achieved a score of 100% in all areas; 100% clearly named the health problem dealt with in the protocol, which was reflected in its contents, and complied with length specifications and absence of formal defects; 80% had a paginated index and 66.7% a definition of compliance, while only 6.7% contained information on organization and functioning, the necessary resources, procedures and evaluation period. In general, the average compliance was less than 50%, except in one guideline, which met 87.5% of the requirements Problems with references were found in 77.7%. In view of the problems detected, a new guide for the drafting of hand hygiene guidelines and protocols is proposed., (Copyright © 2010 Elsevier España S.L. All rights reserved.)

We report three cases of complete rupture of the flexor pollicis longus (FPL) tendon, one case of complete rupture of the index and middle finger flexor digitorum profundus tendons and one case of rupture of the flexor digitorum profundus tendon to the index finger after placement of a volar plate for distal radius fracture. We review the literature and discuss the aetiology of tendon ruptures and techniques to prevent tendon attition., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)