The development and growth of tissues derived from cranial neural crest and primitive mesoderm is dependent on the ligation status of retinoic acid receptor γ:evidence that retinoic acid receptor γ functions to maintain stem/progenitor cells in the absence of retinoic acid

Retinoic acid (RA) signaling is important to normal development. However, the function of the different RA receptors (RARs)-RARα, RARβ, and RARγ-is as yet unclear. We have used wild-type and transgenic zebrafish to examine the role of RARγ. Treatment of zebrafish embryos with an RARγ-specific agonist reduced somite formation and axial length, which was associated with a loss of hoxb13a expression and less-clear alterations in hoxc11a or myoD expression. Treatment with the RARγ agonist also disrupted formation of tissues arising from cranial neural crest, including cranial bones and anterior neural ganglia. There was a loss of Sox 9-immunopositive neural crest stem/progenitor cells in the same anterior regions. Pectoral fin outgrowth was blocked by RARγ agonist treatment. However, there was no loss of Tbx-5-immunopositive lateral plate mesodermal stem/progenitor cells and the block was reversed by agonist washout or by cotreatment with an RARγ antagonist. Regeneration of the caudal fin was also blocked by RARγ agonist treatment, which was associated with a loss of canonical Wnt signaling. This regenerative response was restored by agonist washout or cotreatment with the RARγ antagonist. These findings suggest that RARγ plays an essential role in maintaining stem/progenitor cells during embryonic development and tissue regeneration when the receptor is in its nonligated state.

A study of the regulatory role of retinoic acid receptor gamma in Zebrafish development

Retinoic acid (RA) is thought to signal through retinoic acid receptors (RARs), i.e. RARα, β, and γ to play important roles in embryonic development and tissue regeneration. In this thesis, the zebrafish (Danio rario) was used as a vertebrate model organism to examine the role of RARγ. Treatment of zebrafish embryos with a RARγ specific agonist reduced the axial length of developing embryos, associated with reduced somite number and loss of hoxb13a expression. There were no clear alterations in hoxc11a or myoD expression. Treatment with the RARγ agonist disrupted the formation of anterior structures of the head, the cranial bones and the anterior lateral line ganglia, associated with a loss of sox9 immunopositive cells in the same regions. Pectoral fin outgrowth was blocked by treatment with the RARγ agonist; however, this was not associated with loss of tbx5a immunopositive lateral plate cells and was reversed by wash out of the RARγ agonist or co-treatment with a RARγ antagonist. Regeneration of the transected caudal fin was also blocked by RARγ agonist treatment and restored by agonist washout or antagonist co-treatment; this phenotype was associated with a localised reduction in canonical Wnt signalling. Conversely, elevated canonical Wnt signalling after RARγ treatment was seen in other tissues, including ectopically in the notochord. Furthermore, some phenotypes seen in the RARγ treated embryos were present in mutant zebrafish embryos in which canonical Wnt signalling was constitutively increased. These data suggest that RARγ plays an essential role in maintaining neural crest and mesodermal stem/progenitor cells during normal embryonic development and tissue regeneration when the receptor is in its non-ligated state. In addition, this work has provided evidence that the activation status of RARγ may regulate hoxb13a gene expression and canonical Wnt signalling. Further research is required to confirm such novel regulatory roles.

Étude des mécanismes par lesquels l'acide rétinoïque contrôle l'identité des segments le long de l'axe antéropostérieur

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Remodelage de la chromatine lors de l'activation transcriptionnelle synergique de cdx1 par l'acide rétinoïque et par Wnt3a

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Étude des mécanismes par lesquels l'acide rétinoïque contrôle l'identité des segments le long de l'axe antéropostérieur

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Remodelage de la chromatine lors de l'activation transcriptionnelle synergique de cdx1 par l'acide rétinoïque et par Wnt3a

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Macroalgae contribute to the diet of Patella vulgata from contrasting conditions of latitude and wave exposure in the UK

Analysis of gut contents and stable isotope composition of intertidal limpets (Patella vulgata) showed a major contribution of macroalgae to their diet, along with microalgae and invertebrates. Specimens were collected in areas with limited access to attached macroalgae, suggesting a major dietary component of drift algae. Gut contents of 480 animals from 2 moderately wave-exposed and 2 sheltered rocky shores in each of 2 regions (western Scotland, 55-56°N; and southwest England, 50°N), were analysed in 2 years (n = 30 site-1 yr-1). The abundance of microalgae, macroalgae and invertebrates within the guts was quantified using categorical abundance scales. Gut content composition was compared among regions and wave exposure conditions, showing that the diet of P. vulgata changes with both wave exposure and latitude. Microalgae were most abundant in limpet gut contents in animals from southwestern sites, whilst leathery/corticated macroalgae were more prevalent and abundant in limpets from sheltered and northern sites. P. vulgata appears to have a more flexible diet than previously appreciated, and these keystone grazers consume not only microalgae, but also large quantities of macroalgae and small invertebrates. To date, limpet grazing studies have focussed on their role in controlling recruitment of macroalgae by feeding on microscopic propagules and germlings. Consumption of adult algae suggests that P. vulgata may also directly control the biomass of attached macroalgae on the shore, whilst consumption of drift algae indicates that the species may play important roles in coupling subtidal and intertidal production.

Macroalgae contribute to the diet of Patella vulgata from contrasting conditions of latitude and wave exposure in the UK

Analysis of gut contents and stable isotope composition of intertidal limpets (Patella vulgata) showed a major contribution of macroalgae to their diet, along with microalgae and invertebrates. Specimens were collected in areas with limited access to attached macroalgae, suggesting a major dietary component of drift algae. Gut contents of 480 animals from 2 moderately wave-exposed and 2 sheltered rocky shores in each of 2 regions (western Scotland, 55-56°N; and southwest England, 50°N), were analysed in 2 years (n = 30 site-1 yr-1). The abundance of microalgae, macroalgae and invertebrates within the guts was quantified using categorical abundance scales. Gut content composition was compared among regions and wave exposure conditions, showing that the diet of P. vulgata changes with both wave exposure and latitude. Microalgae were most abundant in limpet gut contents in animals from southwestern sites, whilst leathery/corticated macroalgae were more prevalent and abundant in limpets from sheltered and northern sites. P. vulgata appears to have a more flexible diet than previously appreciated, and these keystone grazers consume not only microalgae, but also large quantities of macroalgae and small invertebrates. To date, limpet grazing studies have focussed on their role in controlling recruitment of macroalgae by feeding on microscopic propagules and germlings. Consumption of adult algae suggests that P. vulgata may also directly control the biomass of attached macroalgae on the shore, whilst consumption of drift algae indicates that the species may play important roles in coupling subtidal and intertidal production.

Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors

Acute myeloid leukemia (AML) is mostly driven by oncogenic transcription factors, which have been classically viewed as intractable targets using small molecule inhibitor approaches. Here, we demonstrate that AML driven by repressive transcription factors including AML1-ETO and PML-RARα are extremely sensitive to Poly (ADP-ribose) Polymerase (PARP) inhibitor (PARPi), in part due to their suppressed expression of key homologous recombination genes and thus compromised DNA damage response (DDR). In contrast, leukemia driven by MLL fusions with dominant transactivation ability is proficient in DDR and insensitive to PARP inhibition. Intriguing, depletion of an MLL downstream target, Hoxa9 that activates expression of various HR genes, impairs DDR and sensitizes MLL leukemia to PARPi. Conversely, Hoxa9 over-expression confers PARPi resistance to AML1-ETO and PML-RARα transformed cells. Together, these studies describe a potential utility of PARPi-induced synthetic lethality for leukemia treatment and reveal a novel molecular mechanism governing PARPi sensitivity in AML.

Auditoria Energética a uma Refinaria de Açúcar

A factura energética possui um peso relativamente reduzido comparativamente com outros factores, como a matéria-prima e a mão-de-obra nos custos de exploração de uma empresa do sector industrial. Devido ao factor referido previamente a gestão de energia era usualmente negligenciada, no entanto, a competitividade industrial aliada à crescente consciencialização para os efeitos nefastos da indústria no meio ambiente conduz ao nascimento do conceito de Utilização Racional de Energia. Como objectivo principal para este trabalho, foi proposta a caracterização energética da RAR – Açúcar, com especial interesse na vertente da energia eléctrica, tendo em vista identificar possíveis melhorias em desempenho técnico e consumos.

Eficacia del aceite de oliva en la prevención de úlceras por presión en pacientes inmovilizados en atención primaria. Ensayo clínico aleatorizado, multicéntrico, paralelo, triple ciego, de no inferioridad

Las úlceras por presión representan un importante problema de salud pública y tienen un importante impacto económico en los sistemas de salud. La mayoría de los estudios para prevenir las úlceras por presión se han llevado a cabo en contextos hospitalarios, usando ácidos grasos hiperoxigenados (AGHO) y hasta la fecha, no se ha realizado ningún estudio específico con aceite de oliva virgen extra (AOVE) en el entorno domiciliario. Material y método Objetivo principal: evaluar si la utilización de AOVE no es inferior a los AGHO en la prevención de úlceras por presión (UPP) en pacientes inmovilizados en el entorno domiciliario. Diseño: Ensayo clínico aleatorizado multicéntrico, paralelo, a triple ciego, de no inferioridad. Ámbito: Población consultante de centros de salud andaluces. Muestra: 831 pacientes inmovilizados en riesgo de padecer UPP. Resultados El período de seguimiento fue de 16 semanas. En el análisis por protocolo, ninguna de las zonas evaluadas presentó diferencias de riesgo de incidencia de las úlceras por presión que superasen el valor delta establecido (10%). Sacro: AOVE 8 (2,55%) vs AGHO 8 (3,08%), RAR 0,53 (-2,2 a 3,26). Talón derecho: AOVE 4 (1,27%) vs AGHO 5 (1,92)%, RAR 0,65 (-1,43 a 2,73). Talón izquierdo: AOVE 3 (0,96%) vs AGHO 3 (1,15%), RAR 0.2 (-1,49 a 1,88). Trocánter Derecho: AOVE 0 (0%) vs AGHO 4 (1,54%), RAR 1,54 (0,04-3,03). Trocánter izquierdo: AOVE 1 (0,32%) vs AGHO 1 (0,38%), RAR 0.07 (-0,91 a 1,04). Discusión Este ensayo clínico pretendía evaluar si la prevención de las UPP usando una fórmula de AOVE no era inferior a la prevención de UPP con el uso AGHO, en el entorno domiciliario y con pacientes inmovilizados de alto riesgo. Los resultados han mostrado esta no inferioridad al no observarse diferencias que hayan superado el límite inferior del intervalo de confianza y convierte al aceite de oliva en un producto eficaz para la prevención de UPP en este tipo de pacientes. Se necesitan más estudios para investigar el mecanismo de acción del AOVE en la prevención de las UPP y relacionarlo con la etiopatogenia de éstas. Bibliografía 1. Gorecki C, Brown JM, Nelson EA, Briggs M, Schoonhoven L, Dealey C, et al. Impact of pressure ulcers on quality of life in older patients: a systematic review. J Am Geriatr Soc. 2009 Jul;57(7):1175–83. 2. Yamamoto Y, Hayashino Y, Higashi T, Matsui M, Yamazaki S, Takegami M, et al. Keeping vulnerable elderly patients free from pressure ulcer is associated with high caregiver burden in informal caregivers. J Eval Clin Pract. 2010 Jun;16(3):585–9. 3. Hanson D, Langemo DK, Anderson J, Thompson P, Hunter S. Friction and shear considerations in pressure ulcer development. Adv Skin Wound Care. 2010 Jan;23(1):21–4. 4. Soldevilla Agreda JJ, Torra i Bou J-E, Verdú Soriano J, López Casanova P. 3.er Estudio Nacional de Prevalencia de Úlceras por Presión en España, 2009: Epidemiología y variables definitorias de las lesiones y pacientes. Gerokomos. 2011 Jun;22(2):77–90. 5. Kottner J, Lahmann N, Dassen T. [Pressure ulcer prevalence: comparison between nursing homes and hospitals]. Pflege Z. 2010 Apr;63(4):228–31. 6. Wilborn D, Halfens R, Dassen T, Tannen A. [Pressure ulcer prevalence in German nursing homes and hospitals: what role does the National Nursing Expert Standard Prevention of Pressure Ulcer play?]. Gesundheitswesen Bundesverb Ärzte Öffentl Gesundheitsdienstes Ger. 2010 Apr;72(4):240–5. 7. Tubaishat A, Anthony D, Saleh M. Pressure ulcers in Jordan: a point prevalence study. J Tissue Viability. 2011 Feb;20(1):14–9. 8. James J, Evans JA, Young T, Clark M. Pressure ulcer prevalence across Welsh orthopaedic units and community hospitals: surveys based on the European Pressure Ulcer Advisory Panel minimum data set. Int Wound J. 2010 Jun;7(3):147–52. 9. Defloor T, Schoonhoven L, Katrien V, Weststrate J, Myny D. Reliability of the European Pressure Ulcer Advisory Panel classification system. J Adv Nurs. 2006 Apr;54(2):189–98

Optical Enhancement of Exoskeleton-Based Estimation of Glenohumeral Angles

In Robot-Assisted Rehabilitation (RAR) the accurate estimation of the patient limb joint angles is critical for assessing therapy efficacy. In RAR, the use of classic motion capture systems (MOCAPs) (e.g., optical and electromagnetic) to estimate the Glenohumeral (GH) joint angles is hindered by the exoskeleton body, which causes occlusions and magnetic disturbances. Moreover, the exoskeleton posture does not accurately reflect limb posture, as their kinematic models differ. To address the said limitations in posture estimation, we propose installing the cameras of an optical marker-based MOCAP in the rehabilitation exoskeleton. Then, the GH joint angles are estimated by combining the estimated marker poses and exoskeleton Forward Kinematics. Such hybrid system prevents problems related to marker occlusions, reduced camera detection volume, and imprecise joint angle estimation due to the kinematic mismatch of the patient and exoskeleton models. This paper presents the formulation, simulation, and accuracy quantification of the proposed method with simulated human movements. In addition, a sensitivity analysis of the method accuracy to marker position estimation errors, due to system calibration errors and marker drifts, has been carried out. The results show that, even with significant errors in the marker position estimation, method accuracy is adequate for RAR.

Inverse kinematics for upper limb compound movement estimation in exoskeleton-assisted rehabilitation

Robot-Assisted Rehabilitation (RAR) is relevant for treating patients affected by nervous system injuries (e.g., stroke and spinal cord injury) -- The accurate estimation of the joint angles of the patient limbs in RAR is critical to assess the patient improvement -- The economical prevalent method to estimate the patient posture in Exoskeleton-based RAR is to approximate the limb joint angles with the ones of the Exoskeleton -- This approximation is rough since their kinematic structures differ -- Motion capture systems (MOCAPs) can improve the estimations, at the expenses of a considerable overload of the therapy setup -- Alternatively, the Extended Inverse Kinematics Posture Estimation (EIKPE) computational method models the limb and Exoskeleton as differing parallel kinematic chains -- EIKPE has been tested with single DOFmovements of the wrist and elbow joints -- This paper presents the assessment of EIKPEwith elbow-shoulder compoundmovements (i.e., object prehension) -- Ground-truth for estimation assessment is obtained from an optical MOCAP (not intended for the treatment stage) -- The assessment shows EIKPE rendering a good numerical approximation of the actual posture during the compoundmovement execution, especially for the shoulder joint angles -- This work opens the horizon for clinical studies with patient groups, Exoskeleton models, and movements types --

Functional analysis of a transcriptional variant of matrix gla protein (MGP)

Dissertação de Mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2014

Comparación de apendicectomía laparoscópica de puerto único con abordaje de 3 puertos, Hospitales "José Carrasco Artega" y "Vicente Corral Moscoso"

Objetivo: Comparar la apendicectomía laparoscópica de puerto único con la de 3 puertos en pacientes con apendicitis aguda, de los hospitales “Vicente Corral Moscoso” y “José Carrasco Arteaga” durante el primer semestre del año 2013. Materiales y método: Estudio experimental que incluyó 170 pacientes de emergencia de los hospitales “Vicente Corral Moscoso” y “José Carrasco Arteaga”; al 50% se le realizó apendicectomía con puerto único (grupo 1) y al restante, se le realizó apendicectomía con 3 puertos (grupo 2). Resultados: De 18 a 25 años fue el grupo mayormente afectado, el sexo masculino predominó en ambos grupos. El tiempo quirúrgico de 61 a 120 minutos fue 61.2% en el grupo 1, el grupo 2 del 55.3%. Dolor posoperatorio leve se presentó en el grupo 1 en 63.5% y en el grupo 2, 41.2%, estancia hospitalaria de 13 a 24 horas en grupo 1 de 62.4%, en el grupo 2, de 25 a 36 horas en 47.1%. Los resultados del puerto único para menor tiempo quirúrgico encontramos un RR de 0,71 (IC –95% 0.4-1.2), RRR 0.29, RAR 0,07 y NNT 15; para intensidad del dolor (leve) RR de 1.54 (IC 95% 1.1-2), RRR -0.54, RAR -0.22 y NNT 5 y para menor estancia hospitalaria (menor a 12 horas) RR = 3.5 de 0.71 (IC 95% 0.75-12.3), RRR -2.5, RAR 0.06 y NNT 17. Conclusión: La apendicectomía laparoscópica con puerto único presenta beneficio únicamente en la intensidad de dolor, en comparación con el acceso de 3 puertos