The Interplay between Cytoskeleton and Calcium Dynamics

Cell motility is a complex cellular event that involves reorganization of cytoskeleton. This reorganization encompasses the transient polarization of the cell to facilitate the plasma membrane ruffling, a rearrangement of cortical actin cytoskeleton required for the development of cellular protrusions. It is known that extracellular Ca2+ influx is essential for cell migration and for the positive-feedback cycle that maintains leading-edge structures and ruffling activity. The aim of this review is to summarize our knowledge regarding the Ca2+-dependent signaling pathways, Ca2+ transporters and sensors involved in cell migration. Also, we show here reported evidences that support for a crosstalk between Ca2+ transport and the reorganization of the cytoskeleton required for cell migration. In this regard, we will analyze the role of store-operated Ca2+ entry (SOCE) as a modulator of cytoskeleton and cell migration, but also the modulation of this Ca2+ entry pathway by microtubules and the actin cytoskeleton. As a main conclusion, this review will show that data reported in the last years support a role for SOCE in shaping cytoskeleton, but at the same time, SOCE is strongly dependent on cytoskeletal proteins, in an interesting interplay between cytoskeleton and Ca2+ dynamics

Mobility assessment in people with Alzheimer disease using smartphone sensors

[EN] Background Understanding the functional status of people with Alzheimer Disease (AD), both in a single (ST) and cognitive dual task (DT) activities is essential for identifying signs of early-stage neurodegeneration. This study aims to compare the performance quality of several tasks using sensors embedded in an Android device, among people at different stages of Alzheimer and people without dementia. The secondary aim is to analyze the effect of cognitive task performance on mobility tasks. Methods This is a cross-sectional study including 22 participants in the control group (CG), 18 in the group with mild AD and 22 in the group with moderate AD. They performed two mobility tests, under ST and DT conditions, which were registered using an Android device. Postural control was measured by medial-lateral and anterior-posterior displacements of the COM (MLDisp and APDisp, respectively) and gait, with the vertical and medial-lateral range of the COM (Vrange and MLrange). Further, the sit-to-stand (PStand) and turning and sit power (PTurnSit), the total time required to complete the test and the reaction time were measured. Results There were no differences between the two AD stages either for ST or DT in any of the variables (p > 0.05). Nevertheless, people at both stages showed significantly lower values of PStand and PTurnSit and larger Total time and Reaction time compared to CG (p < 0.05). Further, Vrange is also lower in CDR1G than in CG (p < 0.05). The DT had a significant deleterious effect on MLDisp in all groups (p < 0.05) and on APDisp only in moderate AD for DT. Conclusions Our findings indicate that AD patients present impairments in some key functional abilities, such as gait, turning and sitting, sit to stand, and reaction time, both in mild and moderate AD. Nevertheless, an exclusively cognitive task only influences the postural control in people with AD.This work was funded by the Spanish Government, Secretaria de Estado de Investigacion, Desarrollo e Innovacion, and co-financed by EU FEDER funds (Grant DPI2013-44227-R). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Serra-Añó, P.; Pedrero, J.; Hurtado-Abellán, J.; Inglés, M.; Espí-López, G.; Lopez Pascual, J. (2019). Mobility assessment in people with Alzheimer disease using smartphone sensors. Journal of NeuroEngineering and Rehabilitation. 16(1). https://doi.org/10.1186/s12984-019-0576-yS161Association A. 2017 Alzheimer’s disease facts and figures. Alzheimers Dement. 2017;13(4):325–73.Harrington MG, Chiang J, Pogoda JM, Gomez M, Thomas K, Marion SD, et al. Executive function changes before memory in preclinical Alzheimer’s pathology: a prospective, cross-sectional, case control study. PLoS One. 2013;8(11):e79378.Buckner RL. Memory and executive function in aging and AD: multiple factors that cause decline and reserve factors that compensate. Neuron. 2004;44(1):195–208.Beauchet O, Launay CP, Barden J, Liu-Ambrose T, Chester VL, Szturm T, et al. Association between falls and brain subvolumes: results from a cross-sectional analysis in healthy older adults. Brain Topogr. 2017;30(2):272–80.Yogev-Seligmann G, Hausdorff JM, Giladi N. The role of executive function and attention in gait. Mov Disord Off J Mov Disord Soc. 2008;23(3):329–42.Verghese J, Wang C, Holtzer R, Lipton R, Xue X. Quantitative gait dysfunction and risk of cognitive decline and dementia. J Neurol Neurosurg Psychiatry. 2007;78(9):929–35.Beauchet O, Annweiler C, Callisaya ML, De Cock A-M, Helbostad JL, Kressig RW, et al. Poor gait performance and prediction of dementia: results from a meta-analysis. J Am Med Dir Assoc. 2016;17(6):482–90.Rucco R, Agosti V, Jacini F, Sorrentino P, Varriale P, De Stefano M, et al. Spatio-temporal and kinematic gait analysis in patients with frontotemporal dementia and Alzheimer’s disease through 3D motion capture. Gait Posture. 2017;52:312–7.de Melo Coelho FG, Stella F, de Andrade LP, Barbieri FA, Santos-Galduróz RF, Gobbi S, et al. Gait and risk of falls associated with frontal cognitive functions at different stages of Alzheimer’s disease. Aging Neuropsychol Cogn. 2012;19(5):644–56.Beauchet O, Allali G, Launay C, Herrmann FR, Annweiler C. Gait variability at fast-pace walking speed: a biomarker of mild cognitive impairment? J Nutr Health Aging. 2013;17(3):235–9.Ganz DA, Bao Y, Shekelle PG, Rubenstein LZ. Will my patient fall? JAMA. 2007;297(1):77–86.Egerton T, Danoudis M, Huxham F, Iansek R. Central gait control mechanisms and the stride length - cadence relationship. Gait Posture. 2011;34(2):178–82.Baddeley AD, Baddeley HA, Bucks RS, Wilcock GK. Attentional control in Alzheimer’s disease. Brain. 2001;124(8):1492–508.Dubois B, Feldman HH, Jacova C, DeKosky ST, Barberger-Gateau P, Cummings J, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS–ADRDA criteria. Lancet Neurol. 2007;6(8):734–46.Coubard OA, Ferrufino L, Boura M, Gripon A, Renaud M, Bherer L. Attentional control in normal aging and Alzheimer’s disease. Neuropsychology. 2011;25(3):353–67.Ries JD, Echternach JL, Nof L, Gagnon BM. Test-retest reliability and minimal detectable change scores for the timed “up & go” test, the six-minute walk test, and gait speed in people with Alzheimer disease. Phys Ther. 2009;89(6):569–79.Tamura K, Kocher M, Finer L, Murata N, Stickley C. Reliability of clinically feasible dual-task tests: expanded timed get up and go test as a motor task on young healthy individuals. Gait Posture. 2018;60:22–7.Muir SW, Speechley M, Wells J, Borrie M, Gopaul K, Montero-Odasso M. Gait assessment in mild cognitive impairment and Alzheimer’s disease: the effect of dual-task challenges across the cognitive spectrum. Gait Posture. 2012;35(1):96–100.Morris JC. The clinical dementia rating (CDR): current version and scoring rules. Neurology. 1993;43(11):2412–4.Ansai JH, Andrade LP, Rossi PG, Takahashi AC, Vale FA, Rebelatto JR. Gait, dual task and history of falls in elderly with preserved cognition, mild cognitive impairment, and mild Alzheimer’s disease. Braz J Phys Ther. 2017;21(2):144–51.Herrero MJ, Blanch J, Peri JM, De Pablo J, Pintor L, Bulbena A. A validation study of the hospital anxiety and depression scale (HADS) in a Spanish population. Gen Hosp Psychiatry. 2003;25(4):277–83.Bower ES, Wetherell JL, Merz CC, Petkus AJ, Malcarne VL, Lenze EJ. A new measure of fear of falling: psychometric properties of the fear of falling questionnaire revised (FFQ-R). Int Psychogeriatr. 2015;27(7):1121–33.López-Pascual J, Hurtado AJ, Inglés M, Espí-López G, Serra-Añó P. P 151-reliability of variables measured with an android device during a modified timed up and go test in patients with Alzheimer’s disease. Gait Posture. 2018;65:484.Nishiguchi S, Yamada M, Nagai K, Mori S, Kajiwara Y, Sonoda T, et al. Reliability and validity of gait analysis by android-based smartphone. Telemed J E Health. 2012;18(4):292–6.Zijlstra W, Hof AL. Assessment of spatio-temporal gait parameters from trunk accelerations during human walking. Gait Posture. 2003;18(2):1–10.Ribeiro JG, De Castro JT, Freire JL. Using the FFT-DDI method to measure displacements with piezoelectric, resistive and ICP accelerometers. In: Conference and exposition on structural dynamics. Rio de Janeiro: Citeseer; 2003.Prieto TE, Myklebust JB, Hoffmann RG, Lovett EG, Myklebust BM. Measures of postural steadiness: differences between healthy young and elderly adults. Biomed Eng IEEE Trans On. 1996;43(9):956–66.Esser P, Dawes H, Collett J, Howells K. IMU: inertial sensing of vertical CoM movement. J Biomech. 2009;42(10):1578–81.Gordon KE, Ferris DP, Kuo AD. Metabolic and mechanical energy costs of reducing vertical center of mass movement during gait. Arch Phys Med Rehabil. 2009;90(1):136–44.Gard SA, Miff SC, Kuo AD. Comparison of kinematic and kinetic methods for computing the vertical motion of the body center of mass during walking. Hum Mov Sci. 2004;22(6):597–610.Weinert-Aplin RA, Twiste M, Jarvis HL, Bennett AN, Baker RJ. Medial-lateral centre of mass displacement and base of support are equally good predictors of metabolic cost in amputee walking. Gait Posture. 2017;51:41–6.Chen S-H, Lo O-Y, Kay T, Chou L-S. Concurrent phone texting alters crossing behavior and induces gait imbalance during obstacle crossing. Gait Posture. 2018;62:422–5.Lindemann U, Claus H, Stuber M, Augat P, Muche R, Nikolaus T, et al. Measuring power during the sit-to-stand transfer. Eur J Appl Physiol. 2003;89(5):466–70.Manckoundia P, Mourey F, Pfitzenmeyer P, Papaxanthis C. Comparison of motor strategies in sit-to-stand and back-to-sit motions between healthy and Alzheimer’s disease elderly subjects. Neuroscience. 2006;137(2):385–92.Christ BU, Combrinck MI, Thomas KG. Both reaction time and accuracy measures of Intraindividual variability predict cognitive performance in Alzheimer’s disease. Front Hum Neurosci. 2018;12:124–35.Vienne A, Barrois RP, Buffat S, Ricard D, Vidal P-P. Inertial sensors to assess gait quality in patients with neurological disorders: a systematic review of technical and analytical challenges. Front Psychol. 2017;8:817.Wang W-H, Chung P-C, Yang G-L, Lin C-W, Hsu Y-L, Pai M-C. An inertial sensor based balance and gait analysis system. In: 2015 IEEE International Symposium on Circuits and Systems (ISCAS): Rio de Janeiro: IEEE; 2015. p. 2636–9.Wüest S, Masse F, Aminian K, Gonzenbach R, De Bruin ED. Reliability and validity of the inertial sensor-based timed “up and go” test in individuals affected by stroke. J Rehabil Res Dev. 2016;53(5):599–610.Nguyen H, Lebel K, Boissy P, Bogard S, Goubault E, Duval C. Auto detection and segmentation of daily living activities during a timed up and go task in people with Parkinson’s disease using multiple inertial sensors. J Neuroengineering Rehabil. 2017;14(1):26.Ansai JH, de Andrade LP, Rossi PG, Nakagawa TH, Vale FAC, Rebelatto JR. Differences in timed up and go subtasks between older people with mild cognitive impairment and mild Alzheimer’s disease. Mot Control. 2018;27:1–12.Eggermont LH, Gavett BE, Volkers KM, Blankevoort CG, Scherder EJ, Jefferson AL, et al. Lower-extremity function in cognitively healthy aging, mild cognitive impairment, and Alzheimer’s disease. Arch Phys Med Rehabil. 2010;91(4):584–8.Leandri M, Cammisuli S, Cammarata S, Baratto L, Campbell J, Simonini M, et al. Balance features in Alzheimer’s disease and amnestic mild cognitive impairment. J Alzheimers Dis. 2009;16(1):113–20.Nakamura T, Meguro K, Yamazaki H, Okuzumi H, Tanaka A, Horikawa A, et al. Postural and gait disturbance correlated with decreased frontal cerebral blood flow in Alzheimer disease. Alzheimer Dis Assoc Disord. 1997;11(3):132–9.Cavagna GA, Margaria R. Mechanics of walking. J Appl Physiol. 1966;21(1):271–8.Ganea R, Paraschiv-Ionescu A, Büla C, Rochat S, Aminian K. Multi-parametric evaluation of sit-to-stand and stand-to-sit transitions in elderly people. Med Eng Phys. 2011;33(9):1086–93.Cameron DM, Bohannon RW, Garrett GE, Owen SV, Cameron DA. Physical impairments related to kinetic energy during sit-to-stand and curb-climbing following stroke. Clin Biomech. 2003;18(4):332–40.McGuinness B, Barrett SL, Craig D, Lawson J, Passmore AP. Attention deficits in Alzheimer’s disease and vascular dementia. J Neurol Neurosurg Psychiatry. 2010;81(2):157–9.Phillips M, Rogers P, Haworth J, Bayer A, Tales A. Intra-individual reaction time variability in mild cognitive impairment and Alzheimer’s disease: gender, processing load and speed factors. PLoS One. 2013;8(6):e65712

Live synthesis of selective carbon dots as fluorescent probes for cobalt determination in water with an automatic microanalyzer

Altres ajuts: acords transformatius de la UABA new strategy integrating the straight synthesis of carbon dots (CDs) and their direct use for the determination of heavy metals by means of fuorescence quenching is presented. The proposal consists of a modular analyzer, which includes a low temperature co-fred ceramics (LTCC) microreactor for the synthesis of CDs and a cyclic olefn copolymer (COC) microfuidic platform, which automatically performs a reverse fow injection analysis (rFIA) protocol for the determination of heavy metal ions in water by CD fuorescence quenching. As a proof of concept, nitrogen-doped CDs were synthesized from acrylic acid and ethylenediamine (ED) with quantum yields (QYs) of up to 44%, which are selective to cobalt. With the described system, we synthesized homogeneous CDs without the need for further purifcation and with the minimum consumption of reagents, and optimized fuorescence measurements can be performed with freshly obtained luminescent nanomaterials that have not undergone decomposition processes. They have an averagehydrodynamic diameter of 4.2±0.9 nm and maximum excitation and emission wavelengths at 358 nm and 452 nm, respectively. The system allows the automatic dilution and bufering of the synthesized CDs and the sample prior to the determination of cobalt. The concentration of cobalt was determined with good sensitivity and a limit of detection of 7 μg·L−1 with a linear range of 0.02-1 mg·L−1 of Co2+. Spiked tap water and river water samples were analyzed, obtaining recovery from 98 to 104%. This demonstrates the potential of the equipment as an efcient on-site control system for heavy metal monitoring in water

Influence of Chemical Enhancers and Iontophoresis on the In Vitro Transdermal Permeation of Propranolol: Evaluation by Dermatopharmacokinetics

[EN] The aims of this study were to assess, in vitro, the possibility of administering propranolol transdermally and to evaluate the usefulness of the dermatopharmacokinetic (DPK) method in assessing the transport of drugs through stratum corneum, using propranolol as a model compound. Four chemical enhancers (decenoic and oleic acid, laurocapram, and R-(+)-limonene) and iontophoresis at two current densities, 0.25 and 0.5 mA/cm(2) were tested. R-(+)-limonene, and iontophoresis at 0.5 mA/cm(2) were proven to be the most efficient in increasing propranolol transdermal flux, both doubled the original propranolol transdermal flux. Iontophoresis was demonstrated to be superior than the chemical enhancer because it allowed faster delivery of the drug. The DPK method was sufficiently sensitive to detect subtle vehicle-induced effects on the skin permeation of propranolol. The shorter duration of these experiments and their ability to provide mechanistic information about partition between vehicle and skin and diffusivity through skin place them as practical and potentially insightful approach to quantify and, ultimately, optimize topical bioavailability.This research was funded by Ministerio de Ciencia e Innovación (AP2007-03456) and the Universidad CEU Cardenal Herrera.Calatayud-Pascual, M.; Sebastian-Morelló, M.; Balaguer-Fernandez, C.; Delgado-Charro, M.; Lopez-Castellano, A.; Merino Sanjuán, V. (2018). Influence of Chemical Enhancers and Iontophoresis on the In Vitro Transdermal Permeation of Propranolol: Evaluation by Dermatopharmacokinetics. Pharmaceutics. 10(4):1-15. https://doi.org/10.3390/pharmaceutics10040265S11510

Effects of Osteopathic Visceral Treatment in Patients with Gastroesophageal Reflux: A Randomized Controlled Trial

Osteopathic manual treatment has been recommended as a non-pharmacological therapy for Gastroesophageal Reflux Disease (GERD). However, to date, no study has supported the effectiveness of this intervention with respect to the symptoms of the disease. Our goal was to assess the effect of an osteopathic manual technique for the lower esophageal sphincter on GERD symptoms, cervical mobility and on the C4 spinous process pressure pain threshold (PPTs). Methods: A randomized, double-blind placebo-controlled trial was performed. Sixty subjects suffering from GERD participated in this study and were randomly assigned to either an experimental group (EG) (n = 29), who received the osteopathic technique for the lower esophageal sphincter, or to a control group (CG) (n = 31), who received a manual contact, which mimicked the osteopathic technique without exerting any therapeutic force. Randomization was computer-generated, with allocation concealed by sequentially numbered, opaque, sealed envelopes. The GerdQ questionnaire was used to assess symptom changes the week after intervention. Cervical Range of Motion (CROM) and algometer were used to evaluate cervical mobility and PPTs before and after both treatments. Before–after between groups comparison (t-test) was used for statistical analysis of the outcome, with two measurement points (GerdQ), while repeated-measures ANOVA was used for those outcomes with four measurement points (CROM and PPT). Results: The application of the osteopathic manual treatment in subjects with GERD produced a significant improvement in symptoms one week after the intervention (p = 0.005) with a between-groups difference of 1.49 points in GerdQ score (95% CI: 0.47–2.49). PPT C4 improved in the EG after the treatment (p = 0.034; η 2 = 0.048) (between-groups difference 8.78 Newton/cm2 ; 95% CI: 0.48–17.09). CROM also increased in the EG compared to the CG (p < 0.001; η 2 = 0.108) (between-groups difference 33.89 degrees; 95% CI: 15.17–52.61). Conclusions: The manual osteopathic technique produces an improvement in GERD symptoms one week after treatment, cervical mobility, and PPTs. This may mean that osteopathic treatment is useful for improving symptoms of GER

Early Response to Dehydration 7 Remodels Cell Membrane Lipid Composition During Cold Stress in Arabidopsis

Plants adjust to unfavorable conditions by altering physiological activities such as gene expression. Although previous studies have identified multiple stress-induced genes, the function of many genes during the stress responses remains unclear. Expression of ERD7 (Early Response to Dehydration 7) is induced in response to dehydration. Here, we show that ERD7 plays essential roles in both plant stress responses and development. In Arabidopsis, ERD7 protein accumulated under various stress conditions including exposure to low temperature. A triple mutant of Arabidopsis lacking ERD7 and two closely-related homologs had an embryonic lethal phenotype, whereas a mutant lacking the two homologs and one ERD7 allele had relatively round leaves, indicating that the ERD7 gene family has essential roles in development. Moreover, the importance of the ERD7 family in stress responses was evidenced by the susceptibility of the mutant lines to cold stress. ERD7 protein was found to bind to several, but not all, negatively charged phospholipids, and was associated with membranes. Lipid components and cold-induced reduction of PIP2 in the mutant line were altered relative to wild type. Furthermore, membranes from the mutant line had reduced fluidity. Taken together, ERD7 and its homologs are important for plant stress responses and development and associated with modification of membrane lipid composition

Small-Packet Flows in Software Defined Networks: Traffic Profile Optimization

This paper proposes a method for optimizing bandwidth usage in Software Defined Networks (SDNs) based on OpenFlow. Flows of small packets presenting a high overhead, as the ones generated by emerging services, can be identified by the SDN controller, in order to remove header fields that are common to any packet in the flow, only during their way through the SDN. At the same time, several packets can be multiplexed together in the same frame, thus reducing the overall number of frames. The method can be useful for providing QoS while the packets are traversing the SDN. Four kinds of small-packet traffic flows are considered (VoIP, UDP and TCP-based online games, and ACKs from TCP flows). Both IPv4 and IPv6 are studied, and significant bandwidth savings (up to 68 % for IPv4 and 78 % for IPv6) can be obtained for the considered kinds of traffic. The optimization method is also applied to different public Internet traffic traces, and significant reductions in terms of packets per second are achieved. Results show that bandwidth consumption is also reduced, especially in those traces where the percentage of small packets is high. Regarding the effect on QoS, the additional delay can be kept very low (below 1 millisecond) when the throughput is high, but it may become significant for low- throughput scenarios. Thus, a trade-off between bandwidth saving and additional delay appears in those cases

Alterations and diagnostic performance of capillary ketonemia in pediatric acute appendicitis: a pilot study

Introduction: The diagnostic performance of capillary ketonemia (CK) has been previously evaluated in context of pediatric acute gastroenteritis. To our knowledge, there is no literature on its performance in the setting of pediatric acute appendicitis (PAA). Materials and methods: In this study, 151 patients were prospectively included and divided into two groups: (1) patients with non-surgical abdominal pain in whom the diagnosis of PAA was excluded (n : 53) and (2) patients with a confirmed diagnosis of PAA (n : 98). In 80 patients (Group 1, n : 23 and group 2, n : 57) a CK was measured at the time of diagnosis. The PAA group was further classified into complicated (n : 18) and uncomplicated PAA (n : 39). Quantitative variables were compared between groups using the Mann-Whitney U test. Diagnostic performance of CK was evaluated with ROC curves. Results: CK values were 0.3 [0.1-0.9] mmol/L in group 1 and 0.7 [0.4-1.4] mmol/L in group 2 (p = 0.01). Regarding the type of PAA, CK values were 0.6 [0.4-0.9] mmol/L in uncomplicated PAA and 1.2 [0.8-1.4] mmol/L in complicated PAA (p : 0.02). The AUC for the discrimination between groups 1 and 2 was 0.68 (95/100 IC 0.53-0.82) (p : 0.24) and the AUC for the discrimination between uncomplicated PAA and complicated PAA was 0.69 (95/100 IC 0.54-0.85) (p : 0.04). The best cut-off point (group 1 vs group 2) resulted in 0.4 mmol/L, with a sensitivity of 80.7/100 and a specificity of 52.2/100. The best cut-off point (non-complicated vs complicated PAA) resulted in 1.1 mmol/L, with a sensitivity of 61.1/100 and a specificity of 76.9/100. Conclusions: This study found significantly higher levels of CK in patients with PAA than in those with NSAP. Similarly, significantly higher levels were observed in patients with complicated than in those with uncomplicated PAA. Nevertheless, the diagnostic performance of CK was only moderate in the two settings analyzed. The potential usefulness of CK determination as a tool to guide the preoperative rehydration regimen of patients with PAA to prevent postoperative hyporexia and vomiting is a promising line of research and should be evaluated in future studies

Bycatch of the European purse-seine tuna fishery in the Atlantic Ocean for the period 2010-2016

This paper presents an update for the period 2010-2016 of the bycatch estimations for the European tuna purse seine fishery operating in the Atlantic Ocean. Bycatch data were collected by observers onboard. Observer coverage increased progressively from 15 trips in 2010, to 114 and 107 trips in 2015 and 2016 respectively. Bycatch data, as collected by the observers, were stratified by quarter and fishing mode (free school and floating object sets). The ratio of total to observed catches of the target species (skipjack, bigeye and yellowfin tunas) in each stratum was then used as raising factor. The average of the annual total bycatch estimated for the studied period was 9,515 t. Tunas (neritic tunas and small size tunas) represent the major part of the bycatch, followed by fin fish, sharks, billfishes, rays and turtles.En prens