Effect of balance training on postural instability in patients with idiopathic Parkinson’s disease

Background. Postural instability (PI) is a disabling sign of Parkinson’s disease (PD) not easily amenable to treatment with medication. Objective. To evaluate the effects of balance training on PI in patients with PD. Methods. A total of 64 patients with PI were randomly assigned to the experimental group (n = 33) for balance training or to the control group (n = 31) for general physical exercises. Each patient received 21 treatment sessions of 50 minutes each. Patients were evaluated by a blinded rater before and after treatment as well as 1 month posttreatment using the Berg Balance Scale (BBS), ActivitiesSpecific Balance Confidence Scale (ABC), postural transfer test, self-destabilization of the center of foot pressure test, number of falls, Unified Parkinson’s Disease Rating Scale (UPDRS), modified Hoehn and Yahr (H&Y) Staging Scale, and Geriatric Depression Scale (GDS). Results. At the end of treatment, the experimental group showed significant improvements in all outcome measures, except for the UPDRS and the H&Y scale. Improvement was maintained at the 1-month follow-up in all outcome measures except for the GDS. No significant changes in performance were observed in the control group. Conclusions. A program of balance training can improve PI in patients with PD

Integració de coneixements: “Donant sentit al que estudia un futur Podòleg”

Memòria final del projecte d'innovació: 2015 PID-UB/017 Integració de coneixements: “Donant sentit al que estudia un futur Podòleg”Al grau de Podologia existeix una certa reticència per part dels estudiants a veure la necessitat d’estudiar conceptes bàsics de matèries de primer que per a ells resulten molt allunyats de la seva futura pràctica professional. L’actual model d’assignatures independents i no coordinades temporalment dificulta la connexió dels coneixements de les diferents matèries de primer. Per aquest motiu ens vam proposar el professorat de Fisiologia, Bioquímica i Biofísica portar a terme el projecte d’integració de coneixements. Aquest projecte s’emmarca en les directrius de l’ESEE i te en compte les noves tendències per promoure curriculums més integrats i interdisciplinaris en el camp de les ciències de la salut (Rosell et al 2002, Vicedo et al. 2009). Aquest projecte s’ha portat a terme durant el primer quadrimestre del curs 2015-16 i s’han elaborat treballs d’integració de coneixements entorn a temes generals i d’altres més específics del camp de la Podologia amb l’objectiu aconseguir una major coordinació entre les diferents disciplines participants i a la vegada proporcionar contextos significatius d’aprenentatge. La iniciativa va tenir una gran acollida per part dels estudiants i es van formar 6 grups de treball d’entre 7-10 participants. Aquesta memòria recull l’experiència realitzada i analitza la incidència positiva del treball d’integració en els resultats de l’assignatura valorats mitjançant enquestes i preguntes específiques d’integració a la prova d’avaluació final

Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory program

Glioblastoma (GBM) still remains an incurable disease being radiotherapy (RT) the mainstay treatment. Glioblastoma intra-tumoral heterogeneity and GlioblastomaInitiating Cells (GICs) challenge the design of effective therapies. We investigated GICs and non-GICs response to RT in a paired in-vitro model and addressed molecular programs activated in GICs after RT. Established GICs heterogeneously expressed several GICs markers and displayed a mesenchymal signature. Upon fractionated RT, GICs reported higher radioresistance compared to non-GICs and showed lower α- and β-values, according to the Linear Quadratic Model interpretation of the survival curves. Moreover, a significant correlation was observed between GICs radiosensitivity and patient disease-free survival. Transcriptome analysis of GICs after acquisition of a radioresistant phenotype reported significant activation of Proneural-to-Mesenchymal transition (PMT) and pro-inflammatory pathways, being STAT3 and IL6 the major players. Our findings support a leading role of mesenchymal GICs in defining patient response to RT and provide the grounds for targeted therapies based on the blockade of inflammatory pathways to overcome GBM radioresistance

Synchrotron-based fourier-transform infrared micro-spectroscopy (SR-FTIRM) fingerprint of the small anionic molecule cobaltabis(dicarbollide) uptake in glioma stem cells

The anionic cobaltabis (dicarbollide) [3,3'-Co(1,2-C2B9H11)2]-, [o-COSAN]-, is the most studied icosahedral metallacarborane. The sodium salts of [o-COSAN]- could be an ideal candidate for the anti-cancer treatment Boron Neutron Capture Therapy (BNCT) as it possesses the ability to readily cross biological membranes thereby producing cell cycle arrest in cancer cells. BNCT is a cancer therapy based on the potential of 10B atoms to produce α particles that cross tissues in which the 10B is accumulated without damaging the surrounding healthy tissues, after being irradiated with low energy thermal neutrons. Since Na[o-COSAN] displays a strong and characteristic ν(B-H) frequency in the infrared range 2.600-2.500 cm-1, we studied the uptake of Na[o-COSAN] followed by its interaction with biomolecules and its cellular biodistribution in two different glioma initiating cells (GICs), mesenchymal and proneural respectively, by using Synchrotron Radiation-Fourier Transform Infrared (FTIR) micro-spectroscopy (SR-FTIRM) facilities at the MIRAS Beamline of ALBA synchrotron light source. The spectroscopic data analysis from the bands in the regions of DNA, proteins, and lipids permitted to suggest that after its cellular uptake, Na[o-COSAN] strongly interacts with DNA strings, modifies proteins secondary structure and also leads to lipid saturation. The mapping suggests the nuclear localization of [o-COSAN]-, which according to reported Monte Carlo simulations may result in a more efficient cell-killing effect compared to that in a uniform distribution within the entire cell. In conclusion, we show pieces of evidence that at low doses, [o-COSAN]- translocates GIC cells' membranes and it alters the physiology of the cells, suggesting that Na[o-COSAN] is a promising agent to BNCT for glioblastoma cells

Preclinical studies with glioblastoma brain organoid co-cultures show efficient 5-ALA photodynamic therapy

Abstract: Background: The high recurrence of glioblastoma (GB) that occurs adjacent to the resection cavity within two years of diagnosis urges an improvement of therapies oriented to GB local control. Photodynamic therapy (PDT) has been proposed to cleanse infiltrating tumor cells from parenchyma to ameliorate short long-term progression-free survival. We examined 5-aminolevulinic acid (5-ALA)- mediated PDT effects as therapeutical treatment and determined optimal conditions for PDT efficacy without causing phototoxic injury to the normal brain tissue. Methods: We used a platform of Glioma Initiation Cells (GICs) infiltrating cerebral organoids with two different glioblastoma cells, GIC7 and PG88. We measured GICs-5-ALA uptake and PDT/5-ALA activity in dose-response curves and the efficacy of the treatment by measuring proliferative activity and apoptosis. Results: 5-ALA (50 and 100  g/mL) was applied, and the release of protoporphyrin IX (PpIX) fluorescence measures demonstrated that the emission of PpIX increases progressively until its stabilization at 24 h. Moreover, decreased proliferation and increased apoptosis corroborated the effect of 5-ALA/PDT on cancer cells without altering normal cells. Conclusions: We provide evidence about the effectiveness of PDT to treat high proliferative GB cells in a complex in vitro system, which combines normal and cancer cells and is a useful tool to standardize new strategic therapies

Synchrotron-Based Fourier-Transform Infrared Micro-Spectroscopy (SR-FTIRM) Fingerprint of the Small Anionic Molecule Cobaltabis(dicarbollide) Uptake in Glioma Stem Cells

The anionic cobaltabis (dicarbollide) [3,3′-Co(1,2-C2B9H11)2]−, [o-COSAN]−, is the most studied icosahedral metallacarborane. The sodium salts of [o-COSAN]− could be an ideal candidate for the anti-cancer treatment Boron Neutron Capture Therapy (BNCT) as it possesses the ability to readily cross biological membranes thereby producing cell cycle arrest in cancer cells. BNCT is a cancer therapy based on the potential of 10B atoms to produce α particles that cross tissues in which the 10B is accumulated without damaging the surrounding healthy tissues, after being irradiated with low energy thermal neutrons. Since Na[o-COSAN] displays a strong and characteristic ν(B-H) frequency in the infrared range 2.600–2.500 cm−1, we studied the uptake of Na[o-COSAN] followed by its interaction with biomolecules and its cellular biodistribution in two different glioma initiating cells (GICs), mesenchymal and proneural respectively, by using Synchrotron Radiation-Fourier Transform Infrared (FTIR) micro-spectroscopy (SR-FTIRM) facilities at the MIRAS Beamline of ALBA synchrotron light source. The spectroscopic data analysis from the bands in the regions of DNA, proteins, and lipids permitted to suggest that after its cellular uptake, Na[o-COSAN] strongly interacts with DNA strings, modifies proteins secondary structure and also leads to lipid saturation. The mapping suggests the nuclear localization of [o-COSAN]−, which according to reported Monte Carlo simulations may result in a more efficient cell-killing effect compared to that in a uniform distribution within the entire cell. In conclusion, we show pieces of evidence that at low doses, [o-COSAN]− translocates GIC cells’ membranes and it alters the physiology of the cells, suggesting that Na[o-COSAN] is a promising agent to BNCT for glioblastoma cells.The authors received support from the Spanish Ministry of Health and Consumer Afairs, the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER) FIS-PI18/00916. This work has been supported by the Spanish Ministerio de Economía y Competitividad (PID2019-106832RB-I00), the Generalitat de Catalunya (2017SGR1720) and CELLSALBA Synchroton (Ref.: 2019023533). Miquel Nuez is enrolled in the PhD program of the UAB.Peer reviewe

Molecular mechanisms underlying radioresistance of glioblastoma initiating cells

[eng] Glioblastoma (GBM) is the most frequent and malignant primary brain tumor. The current standard of care for adult patient with diagnosed GBM is surgery followed by radiotherapy (RT) plus concomitant and adjuvant temozolomide (TMZ) chemotherapy. Despite intense patient management, conventional therapies are not able to achieve long-term remissions and eventually almost every tumor recurs. The impossibility of extensive tumor debulking, the marked heterogeneity of lesions, the poor drug delivery in the brain and the presence of cancer cells with stem features (Cancer Stem Cells, CSCs) within the bulk of the tumor contribute significantly to the lack of effective treatment options. We ought to develop an in-vitro model to investigate molecular mechanisms underlying GBM resistance based on two major cornerstones: (i) the key duality between Glioblastoma Initiating Cells (GICs) and the bulk of the tumor; and (ii) the intratumoral heterogeneity. Consequently, we conceived a paired model where both GICs and differentiated GBM cells depicting the bulk of the tumor were represented. Both culture models were derived from the same GBM post- surgical specimen, but were established and maintained in different culturing conditions. Moreover, we aimed to design a model that could preserve as much as possible the intratumoral heterogeneity of GBM, within the known limits of in-vitro cultures. Consequently, cultures obtained from GBM specimens were not sorted for expression of putative cancer stem cells markers. Six different GBM patients’ samples were processed and established in-vitro as both Differentiated Glial Cells (DGC) and GICs cultures. Established GICs cultures and corresponding tumor-of-origin were analysed according to the molecular subtypes defined on the basis of transcriptomic signature and both were classified as predominantly Mesenchymal. DGC and GICs deriving from the same patient and growing in cultures as monolayer and neurospheres respectively, were compared side-by-side and stem’s functional features and markers expression were investigated. Neurosphere cultures demonstrated to be enriched in GICs, whereas monolayer cultures were not, as indicated by their poor clonogenic capacity and absent CSCs markers expression. In addition, CSCs markers’ expression patterns highlighted the heterogeneous nature of GICs cultures. Consequently, we demonstated that the neurosphere culture method is a proper approach to isolate GICs within the GBM tumor mass, preserving GICs heterogenic nature. Radiosensitivity of four established culture pairs was investigated by means of clonogenic assay and all established unsorted GICs-enriched cultures ended up being more radioresistant than their differentiated counterparts. Importantly, radiation response of irradiated GICs, but not of DGC, correlates with patient’s outcome, thus supporting the GICs leading role in defining patient treatment response. In conclusion, we propose a quick and affordable method to faithfully determine cancer cells’ treatment response and potentially predict patient outcome based on empirical data. Following clinically relevant fractionated radiotherapy we detected, by means of transcriptomic analysis, marked activation of inflammatory-related pathways, ECM remodeling, cell migration and intercellular crosstalk in GICs. Strikingly, several genes pointed to epithelial/mesenchymal transition processes via IL6/JAK/STAT3 and TNF-α/NFkβ pathways. A small signature of radiation-induced Mes-associated genes was defined in GICs: ICAM1, COX2, CTGF, IL6, LIF and NNMT. In addition, the possible involvement of ITGA6 in GICs response to ionizing radiation was investigated. The knock-down of ITGA6 in GICs-enriched culture enhanced their radiosensitivity, potentially improving tumor radiocurability, and reported decreased capacity to retain stemness after radiotherapy.[spa] El Glioblastoma (GBM) es el tumor cerebral primario maligno más frecuente en adultos. El tratamiento actual, consiste en cirugía seguida de radioterapia (RT) más quimioterapia, no evita las recidivas a largo plazo. Para investigar los mecanismos moleculares que subyacen a la resistencia de GBM a la RT, se ha desarrollado un modelo in-vitro basado en dos pilares fundamentales: (i) la dualidad entre las Glioblastoma Initiating Cells (GICs) y el resto de células neoplásicas (células diferenciadas, DGC); y (ii) la heterogeneidad intratumoral. Los cultivos de GICs y las muestras de tumor homólogas se clasificaron como de tipo mesenquimal. Se compararon los cultivos DGC y GICs por sus características funcionales y metabólicas, la expresión de marcadores de células madres tumorales y la respuesta a la RT. Los cultivos GICs demostraron estar enriquecidos en CSCs, y el patrón de expresión de marcadores de CSCs evidenció su heterogeneidad, a diferencia de lo observado en DGC. Además, todos los cultivos enriquecidos en GICs fueron, a largo plazo, más resistentes a la RT en comparación con sus homólogos diferenciados. Es importante destacar que la radioresistencia de las GICs, pero no de las DGC, se correlaciona con el pronóstico de los pacientes, apoyando así el papel de las GICs en la respuesta al tratamiento. En conclusión, se propone un método rápido y económico para determinar fielmente la respuesta al tratamiento con RT de las células tumorales y potencialmente predecir la evolución del paciente basado en datos empíricos. Para entender mejor el fenómeno de la resistencia a la RT de las GICs se realizó un análisis transcriptómico de DGC y GICs postirradiación. Exclusivamente en las GICs se detectó una activación significativa de las vías relacionadas con la inflamación, remodelación de la matriz extracelular, migración celular, interacción célula-célula y transición epitelio- mesénquima mediado por STAT3 y NF-κβ. Se identificó un grupo de genes asociados al perfil mesenquimal e inducidos por la radiación en GICs: ICAM1, COX2, CTGF, IL-6, LIF y NNMT. Finalmente, se investigó la posible implicación de ITGA6, previamente descrito como marcador de CSCs en GBM, en la respuesta de GICs a la RT. La inhibición de ITGA6 en los cultivos enriquecidos en GICs aumentó la sensibilidad a la RT, mejorando potencialmente la respuesta al tratamiento

Analysis of artist’s palette on a 16th century wood panel painting by portable and laboratory Raman instruments

International audienceNon-destructive analysis of the artist’s palette of ancient wooden panel paintings is a difficult task and studies are rare. Here we compare different methods of analysis of a wooden panel painting, dated to the early sixteenth century, mainly by Raman and infrared spectroscopies. Raman spectra were recorded on collected/sampled micrometric fragments using portable Raman instruments with laser excitation lines at 532 and 785 nm and transportable Raman instruments at 532, 633 and 785 nm; a fixed 1064 nm Raman spectrometer was also used. Infrared analyses were performed in Attenuated Total Reflection (ATR-FTIR) mode. Using the portable instrument, the Raman spectra evidenced white lead, calcite and vermilion only. Raman spectra recorded by transportable and fixed instruments enabled the identification of most of the artist’s palette: (i) white lead, calcite, gypsum and cerussite for white colour; (ii) vermilion, red lead, litharge, haematite for red; (iii) azurite, indigo and lapis lazuli for blue. IR spectra gave information on the organic binding media. XRF analysis on a brown pigment suggested an heterogeneous mixture of a red pigment (such as haematite and/or minium) and a green one as malachite. GC-MS analysis allowed identifying terpenic resin in the composition of the outer protective layer

Effect of balance training on postural instability in patients with idiopathic Parkinson\u2019s disease

Background. Postural instability (PI) is a disabling sign of Parkinsong's disease (PD) not easily amenable to treatment with medication. Objective. To evaluate the effects of balance training on PI in patients with PD. Methods. A total of 64 patients with PI were randomly assigned to the experimental group (n = 33) for balance training or to the control group (n = 31) for general physical exercises. Each patient received 21 treatment sessions of 50 minutes each. Patients were evaluated by a blinded rater before and after treatment as well as 1 month posttreatment using the Berg Balance Scale (BBS), Activities-Specific Balance Confidence Scale (ABC), postural transfer test, self-destabilization of the center of foot pressure test, number of falls, Unified Parkinsong's Disease Rating Scale (UPDRS), modified Hoehn and Yahr (H&Y) Staging Scale, and Geriatric Depression Scale (GDS). Results.At the end of treatment, the experimental group showed significant improvements in all outcome measures, except for the UPDRS and the H&Y scale. Improvement was maintained at the 1-month follow-up in all outcome measures except for the GDS. No significant changes in performance were observed in the control group. Conclusions. A program of balance training can improve PI in patients with PD

Integració de coneixements: “Donant sentit al que estudia un futur Podòleg”

Memòria final del projecte d'innovació: 2015 PID-UB/017 Integració de coneixements: “Donant sentit al que estudia un futur Podòleg”Al grau de Podologia existeix una certa reticència per part dels estudiants a veure la necessitat d’estudiar conceptes bàsics de matèries de primer que per a ells resulten molt allunyats de la seva futura pràctica professional. L’actual model d’assignatures independents i no coordinades temporalment dificulta la connexió dels coneixements de les diferents matèries de primer. Per aquest motiu ens vam proposar el professorat de Fisiologia, Bioquímica i Biofísica portar a terme el projecte d’integració de coneixements. Aquest projecte s’emmarca en les directrius de l’ESEE i te en compte les noves tendències per promoure curriculums més integrats i interdisciplinaris en el camp de les ciències de la salut (Rosell et al 2002, Vicedo et al. 2009). Aquest projecte s’ha portat a terme durant el primer quadrimestre del curs 2015-16 i s’han elaborat treballs d’integració de coneixements entorn a temes generals i d’altres més específics del camp de la Podologia amb l’objectiu aconseguir una major coordinació entre les diferents disciplines participants i a la vegada proporcionar contextos significatius d’aprenentatge. La iniciativa va tenir una gran acollida per part dels estudiants i es van formar 6 grups de treball d’entre 7-10 participants. Aquesta memòria recull l’experiència realitzada i analitza la incidència positiva del treball d’integració en els resultats de l’assignatura valorats mitjançant enquestes i preguntes específiques d’integració a la prova d’avaluació final