Reinforced feedback in virtual environment for rehabilitation of upper extremity dysfunction after stroke: preliminary data from a randomized controlled trial.

OBJECTIVES: To study whether the reinforced feedback in virtual environment (RFVE) is more effective than traditional rehabilitation (TR) for the treatment of upper limb motor function after stroke, regardless of stroke etiology (i.e., ischemic, hemorrhagic). DESIGN: Randomized controlled trial. Participants. Forty-four patients affected by stroke. Intervention. The patients were randomized into two groups: RFVE (N = 23) and TR (N = 21), and stratified according to stroke etiology. The RFVE treatment consisted of multidirectional exercises providing augmented feedback provided by virtual reality, while in the TR treatment the same exercises were provided without augmented feedbacks. Outcome Measures. Fugl-Meyer upper extremity scale (F-M UE), Functional Independence Measure scale (FIM), and kinematics parameters (speed, time, and peak). RESULTS: The F-M UE (P = 0.030), FIM (P = 0.021), time (P = 0.008), and peak (P = 0.018), were significantly higher in the RFVE group after treatment, but not speed (P = 0.140). The patients affected by hemorrhagic stroke significantly improved FIM (P = 0.031), time (P = 0.011), and peak (P = 0.020) after treatment, whereas the patients affected by ischemic stroke improved significantly only speed (P = 0.005) when treated by RFVE. CONCLUSION: These results indicated that some poststroke patients may benefit from RFVE program for the recovery of upper limb motor function. This trial is registered with NCT01955291

E-cadherin expression is associated with somatostatin analogue response in acromegaly

Acromegaly is a rare disease resulting from hypersecretion of growth hormone (GH) and insulin‐like growth factor 1 (IGF1) typically caused by pituitary adenomas, which is associated with increased mortality and morbidity. Somatostatin analogues (SSAs) represent the primary medical therapy for acromegaly and are currently used as first‐line treatment or as second‐line therapy after unsuccessful pituitary surgery. However, a considerable proportion of patients do not adequately respond to SSAs treatment, and therefore, there is an urgent need to identify biomarkers predictors of response to SSAs. The aim of this study was to examine E‐cadherin expression by immunohistochemistry in fifty‐five GH‐producing pituitary tumours and determine the potential association with response to SSAs as well as other clinical and histopathological features. Acromegaly patients with tumours expressing low E‐cadherin levels exhibit a worse response to SSAs. E‐cadherin levels are associated with GH‐producing tumour histological subtypes. Our results indicate that the immunohistochemical detection of E‐cadherin might be useful in categorizing acromegaly patients based on the response to SSAs.ISCIII‐Subdirección General de Evaluación y Fomento de la Investigación PI13/02043 PI16/00175FEDER PI13/02043 PI16/00175Junta de Andalucía A‐0023‐2015 A‐0003‐2016 CTS‐1406 BIO‐0139Andalusian Ministry of Health C‐0015‐2014CIBERobn PI13/ 02043 PI16/0017

Virtual reality and physiotherapy in post-stroke functional re-education of the lower extremity: A controlled clinical trial on a new approach

Numerous Virtual Reality (VR) systems address post-stroke functional recovery of the lower extremity (LE), most of them with low early applicability due to the gait autonomy they require. The aim of the present study was to evaluate the feasibility of a specific VR treatment and its clinical effect on LE functionality, gait, balance, and trunk control post-stroke. A controlled, prospective, clinical trial was carried out with 20 stroke patients, who were divided into two groups: the first group (VR + CP; n = 10) received combined therapy of 1 h VR and 1 h of conventional physiotherapy (CP) and the second group (CP; n = 10) received 2 h of CP (5 days/week, for 3 weeks). The following pre-post-intervention measuring scales were used: Functional Ambulatory Scale (FAC), Functional Independence Measure (FIM), Fugl-Meyer Assessment (FM), Berg Balance Scale (BBS), and Trunk Control Test (TCT). Only VR + CP showed a significant improvement in FAC. In FIM, CP presented a tendency to significance, whereas VR + CP showed significance. Both groups improved significantly in FM (especially in amplitude/pain in VR + CP and in sensitivity in CP) and in BBS. In TCT, there was a non-significant improvement in both groups. The results indicate that the intervention with VR is a feasible treatment in the post-stroke functional re-education of the LE, with the potential to be an optimal complement of CP

A pilot randomised controlled trial on the effectiveness of infant massage on the acceptance, commitment and awareness of influence in parents of babies with Down syndrome

Background The emotional state of parents of babies with Down syndrome affects their babies’ development and their parent–child bonding. The aim for this study was to conduct a pilot randomised controlled evaluation of the effect of infant massage on parents of babies with Down syndrome. Methods This pilot study compared two groups (intervention and control), each with 16 parents of babies with Down syndrome. Indices of acceptance, engagement and awareness of influence were measured at two different time points (pre-test and after 5 weeks) using the ‘This Is My Baby’ Interview. The allocation of families to each group was randomised. The experimental group performed infant massage, applied by the parents, for 5 weeks, every day for at least 10 min. The massage protocol was based on the methodology created by Vimala McClure. Parents in the control group received the intervention after completion of the study. Results The indices of acceptance, commitment and awareness of influence improved in the experimental group and in the control group. The 2 × 2 mixed-model analysis of variance indicates a statistically significant group-by-time interaction for all indices (P < 0.001), which was significantly higher in the experimental group than in the control group. Conclusions The application of infant massage, by parents to their babies, improves the rates of acceptance, commitment and awareness of influence of parents of babies with Down syndrome in the short termFunding for open access charge: Universidad de Málaga / CBU

Feigenbaum graphs: a complex network perspective of chaos

The recently formulated theory of horizontal visibility graphs transforms time series into graphs and allows the possibility of studying dynamical systems through the characterization of their associated networks. This method leads to a natural graph-theoretical description of nonlinear systems with qualities in the spirit of symbolic dynamics. We support our claim via the case study of the period-doubling and band-splitting attractor cascades that characterize unimodal maps. We provide a universal analytical description of this classic scenario in terms of the horizontal visibility graphs associated with the dynamics within the attractors, that we call Feigenbaum graphs, independent of map nonlinearity or other particulars. We derive exact results for their degree distribution and related quantities, recast them in the context of the renormalization group and find that its fixed points coincide with those of network entropy optimization. Furthermore, we show that the network entropy mimics the Lyapunov exponent of the map independently of its sign, hinting at a Pesin-like relation equally valid out of chaos.Comment: Published in PLoS ONE (Sep 2011

Splicing Machinery is Dysregulated in Pituitary Neuroendocrine Tumors and is Associated with Aggressiveness Features

Pituitary neuroendocrine tumors (PitNETs) constitute approximately 15% of all brain tumors, and most have a sporadic origin. Recent studies suggest that altered alternative splicing and, consequently, appearance of aberrant splicing variants, is a common feature of most tumor pathologies. Moreover, spliceosome is considered an attractive therapeutic target in tumor pathologies, and the inhibition of SF3B1 (e.g., using pladienolide-B) has been shown to exert antitumor effects. Therefore, we aimed to analyze the expression levels of selected splicing-machinery components in 261 PitNETs (somatotropinomas/non-functioning PitNETS/corticotropinomas/prolactinomas) and evaluated the direct effects of pladienolide-B in cell proliferation/viability/hormone secretion in human PitNETs cell cultures and pituitary cell lines (AtT-20/GH3). Results revealed a severe dysregulation of splicing-machinery components in all the PitNET subtypes compared to normal pituitaries and a unique fingerprint of splicing-machinery components that accurately discriminate between normal and tumor tissue in each PitNET subtype. Moreover, expression of specific components was associated with key clinical parameters. Interestingly, certain components were commonly dysregulated throughout all PitNET subtypes. Finally, pladienolide-B reduced cell proliferation/viability/hormone secretion in PitNET cell cultures and cell lines. Altogether, our data demonstrate a drastic dysregulation of the splicing-machinery in PitNETs that might be associated to their tumorigenesis, paving the way to explore the use of specific splicing-machinery components as novel diagnostic/prognostic and therapeutic targets in PitNETs

Homogeneous immunoassay for cyclopiazonic acid based upon mimotopes and upconversion-resonance energy transfer

Strains of Penicillium spp. are used for fungi-ripened cheeses and Aspergillus spp. routinely contaminate maize and other crops. Some of these strains can produce toxic secondary metabolites (mycotoxins), including the neurotoxin α-cyclopiazonic acid (CPA). In this work, we developed a homogeneous upconversion-resonance energy transfer (UC-RET) immunoassay for the detection of CPA using a novel epitope mimicking peptide, or mimotope, selected by phage display. CPA-specific antibody was used to isolate mimotopes from a cyclic 7-mer peptide library in consecutive selection rounds. Enrichment of antibody binding phages was achieved, and the analysis of individual phage clones revealed four different mimotope peptide sequences. The mimotope sequence, ACNWWDLTLC, performed best in phage-based immunoassays, surface plasmon resonance binding analyses, and UC-RET-based immunoassays. To develop a homogeneous assay, upconversion nanoparticles (UCNP, type NaYF4:Yb3+, Er3+) were used as energy donors and coated with streptavidin to anchor the synthetic biotinylated mimotope. Alexa Fluor 555, used as an energy acceptor, was conjugated to the anti-CPA antibody fragment. The homogeneous single-step immunoassay could detect CPA in just 5 min and enabled a limit of detection (LOD) of 30 pg mL-1 (1.5 μg kg-1) and an IC50 value of 0.36 ng mL-1. No significant cross-reactivity was observed with other co-produced mycotoxins. Finally, we applied the novel method for the detection of CPA in spiked maize samples using high-performance liquid chromatography coupled to a diode array detector (HPLC-DAD) as a reference method.This work has been funded by the Ministry of Science, Innovation and Universities (MSIU) (RTI2018-096410-B-C21, PID2021-127457OB-C21 and PID2019-105237 GB-I00). FP acknowledges the MSIU for an FPU contract.S

Long-term monitoring of the Iberian ibex population in the Sierra Nevada of the southeast Iberian Peninsula

This dataset provides long-term information on the presence of the Iberian ibex (Capra pyrenaica hispanica Schimper, 1848) in Sierra Nevada (SE Iberian Peninsula). Data on the abundance and demographic structure of the Iberian ibex population were compiled over the last three decades. Transects were laid out to record different variables such as the number of individuals sighted, the perpendicular distance of each group of Iberian ibex to the transect line and sex as well as age of individuals in the case of males. These data enabled the calculation of population parameters such as density, sex ratio, birth rate, and age structure. These parameters are key for Iberian ibex conservation and management, given that Sierra Nevada harbours the largest population of this species in the Iberian Peninsula. The data set we present is structured using the Darwin Core biological standard, which contains 3,091 events (582 transect walk events and 2,509 group sighting events), 5,396 occurrences, and 2,502 measurements. The occurrences include the sightings of 11,436 individuals (grouped by sex and age) from 1993 to 2018 in a total of 88 transects distributed along Sierra Nevada, of which 33 have been continuously sampled since 2008.Projects "LIFE-ADAPTAMED: Protection of key ecosystem services by adaptive management of Climate Change endangered Mediterranean socioecosystems" LIFE14 CCA/ES/000612H2020 project "ECOPOTENTIAL: Improving future ecosystem benefits through earth observations" - European Union's Horizon 2020 research and innovation programme 641762Elter H2020 project "European Long-Term Ecosystem and Socio-Ecological Research Infrastructure" - European Union's Horizon 2020 programme 654359100100031005001010040016676/2006/A/001571/2007/M/00173/2009/M/00861/11/M/0003/15/M/002016 _00014_M2017-00189

Recombinant Peptide Mimetic NanoLuc Tracer for Sensitive Immunodetection of Mycophenolic Acid

Mycophenolic acid (MPA) is an immunosuppressant drug commonly used to prevent organ rejection in transplanted patients. MPA monitoring is of great interest due to its small therapeutic window. In this work, a phage-displayed peptide library was used to select cyclic peptides that bind to the MPA-specific recombinant antibody fragment (Fab) and mimic the behavior of MPA. After biopanning, several phage-displayed peptides were isolated and tested to confirm their epitope-mimicking nature in phage-based competitive immunoassays. After identifying the best MPA mimetic (ACEGLYAHWC with a disulfide constrained loop), several immunoassay approaches were tested, and a recombinant fusion protein containing the peptide sequence with a bioluminescent enzyme, NanoLuc, was developed. The recombinant fusion enabled its direct use as the tracer in competitive immunoassays without the need for secondary antibodies or further labeling. A bioluminescent sensor, using streptavidin-coupled magnetic beads for the immobilization of the biotinylated Fab antibody, enabled the detection of MPA with a detection limit of 0.26 ng mL(-1) and an IC50 of 2.9 +/- 0.5 ng mL(-1). The biosensor showed good selectivity toward MPA and was applied to the analysis of the immunosuppressive drug in clinical samples, of both healthy and MPA-treated patients, followed by validation by liquid chromatography coupled to diode array detection

A Somatostatin Receptor Subtype-3 (SST3) Peptide Agonist Shows Antitumor Effects in Experimental Models of Nonfunctioning Pituitary Tumors

[Purpose] Somatostatin analogues (SSA) are efficacious and safe treatments for a variety of neuroendocrine tumors, especially pituitary neuroendocrine tumors (PitNET). Their therapeutic effects are mainly mediated by somatostatin receptors SST2 and SST5. Most SSAs, such as octreotide/lanreotide/pasireotide, are either nonselective or activate mainly SST2. However, nonfunctioning pituitary tumors (NFPTs), the most common PitNET type, mainly express SST3 and finding peptides that activate this particular somatostatin receptor has been very challenging. Therefore, the main objective of this study was to identify SST3-agonists and characterize their effects on experimental NFPT models.[Experimental Design] Binding to SSTs and cAMP level determinations were used to screen a peptide library and identify SST3-agonists. Key functional parameters (cell viability/caspase activity/chromogranin-A secretion/mRNA expression/intracellular signaling pathways) were assessed on NFPT primary cell cultures in response to SST3-agonists. Tumor growth was assessed in a preclinical PitNET mouse model treated with a SST3-agonist. [Results] We successfully identified the first SST3-agonist peptides. SST3-agonists lowered cell viability and chromogranin-A secretion, increased apoptosis in vitro, and reduced tumor growth in a preclinical PitNET model. As expected, inhibition of cell viability in response to SST3-agonists defined two NFPT populations: responsive and unresponsive, wherein responsive NFPTs expressed more SST3 than unresponsive NFPTs and exhibited a profound reduction of MAPK, PI3K-AKT/mTOR, and JAK/STAT signaling pathways upon SST3-agonist treatments. Concurrently, SSTR3 silencing increased cell viability in a subset of NFPTs. [Conclusions] This study demonstrates that SST3-agonists activate signaling mechanisms that reduce NFPT cell viability and inhibit pituitary tumor growth in experimental models that expresses SST3, suggesting that targeting this receptor could be an efficacious treatment for NFPTs.This work has been funded by the following grants: Junta de Andalucía [CTS-1406 (R.M. Luque), BIO-0139 (J.P. Castaño)]; Ministerio de Ciencia, Innovación y Universidades [BFU2016-80360-R (J.P. Castaño)] and Instituto de Salud Carlos III, co-funded by European Union [ERDF/ESF, “Investing in your future”: PI16/00264 (R.M. Luque), CP15/00156 (M.D. Gahete) and CIBERobn]. CIBER is an initiative of Instituto de Salud Carlos III