Age-related changes to motor synergies in multi-joint and multi-finger manipulative skills: a meta-analysis

Purpose The aim of the current meta-analysis was to examine the extent to which there are differences in upper extremity motor synergies across different age groups in manipulative tasks. Methods The studies that used the uncontrolled manifold method to examine the effect of age on motor synergies in multijoint and multi-finger tasks were selected. Sixteen relevant studies from 1154 articles were selected for the meta-analysis—4 and 12 studies considered multi-joint kinematics and multi-finger kinetic tasks respectively. Results The results of the meta-analysis suggested reduced strength of synergies in multi-finger task in older adults, but this was not the case for synergies in multi-joint task. Part of this age-related difference in finger function is related to the increased variability in total force in grasping tasks. However, reductions in the strength of multi-finger synergies in hand functions following ageing appear to depend on the characteristics of the task. Conclusions These findings indicate that the cooperation among fingers to stabilise the total required force to apply for grasping and other fine motor skills is less efficient in older adults that might affect the quality of manipulative tasks

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Genetic variation among species, races, forms and inbred lines of lac insects belonging to the genus Kerria (Homoptera, Tachardiidae)

The lac insects (Homoptera: Tachardiidae), belonging to the genus Kerria, are commercially exploited for the production of lac. Kerria lacca is the most commonly used species in India. RAPD markers were used for assessing genetic variation in forty-eight lines of Kerria, especially among geographic races, infrasubspecific forms, cultivated lines, inbred lines, etc., of K. lacca. In the 48 lines studied, the 26 RAPD primers generated 173 loci, showing 97.7% polymorphism. By using neighbor-joining, the dendrogram generated from the similarity matrix resolved the lines into basically two clusters and outgroups. The major cluster, comprising 32 lines, included mainly cultivated lines of the rangeeni form, geographic races and inbred lines of K. lacca. The second cluster consisted of eight lines of K. lacca, seven of the kusmi form and one of the rangeeni from the southern state of Karnataka. The remaining eight lines formed a series of outgroups, this including a group of three yellow mutant lines of K. lacca and other species of the Kerria studied, among others. Color mutants always showed distinctive banding patterns compared to their wild-type counterparts from the same population. This study also adds support to the current status of kusmi and rangeeni, as infraspecific forms of K. lacca

Desire and Dread from the Nucleus Accumbens: Cortical Glutamate and Subcortical GABA Differentially Generate Motivation and Hedonic Impact in the Rat

Background: GABAergic signals to the nucleus accumbens (NAc) shell arise from predominantly subcortical sources whereas glutamatergic signals arise mainly from cortical-related sources. Here we contrasted GABAergic and glutamatergic generation of hedonics versus motivation processes, as a proxy for comparing subcortical and cortical controls of emotion. Local disruptions of either signals in medial shell of NAc generate intense motivated behaviors corresponding to desire and/or dread, along a rostrocaudal gradient. GABA or glutamate disruptions in rostral shell generate appetitive motivation whereas disruptions in caudal shell elicit fearful motivation. However, GABA and glutamate signals in NAc differ in important ways, despite the similarity of their rostrocaudal motivation gradients. Methodology/Principal Findings: Microinjections of a GABAA agonist (muscimol), or of a glutamate AMPA antagonist (DNQX) in medial shell of rats were assessed for generation of hedonic ‘‘liking’ ’ or ‘‘disliking’ ’ by measuring orofacial affective reactions to sucrose-quinine taste. Motivation generation was independently assessed measuring effects on eating versus natural defensive behaviors. For GABAergic microinjections, we found that the desire-dread motivation gradient was mirrored by an equivalent hedonic gradient that amplified affective taste ‘‘liking’ ’ (at rostral sites) versus ‘‘disliking’ ’ (at caudal sites). However, manipulation of glutamatergic signals completely failed to alter pleasure-displeasure reactions to sensory hedonic impact, despite producing a strong rostrocaudal gradient of motivation

Reflections on the ethics of recruiting foreign-trained human resources for health

<p>Abstract</p> <p>Background</p> <p>Developed countries' gains in health human resources (HHR) from developing countries with significantly lower ratios of health workers have raised questions about the ethics or fairness of recruitment from such countries. By attracting and/or facilitating migration for foreign-trained HHR, notably those from poorer, less well-resourced nations, recruitment practices and policies may be compromising the ability of developing countries to meet the health care needs of their own populations. Little is known, however, about actual recruitment practices. In this study we focus on Canada (a country with a long reliance on internationally trained HHR) and recruiters working for Canadian health authorities.</p> <p>Methods</p> <p>We conducted interviews with health human resources recruiters employed by Canadian health authorities to describe their recruitment practices and perspectives and to determine whether and how they reflect ethical considerations.</p> <p>Results and discussion</p> <p>We describe the methods that recruiters used to recruit foreign-trained health professionals and the systemic challenges and policies that form the working context for recruiters and recruits. HHR recruiters' reflections on the global flow of health workers from poorer to richer countries mirror much of the content of global-level discourse with regard to HHR recruitment. A predominant market discourse related to shortages of HHR outweighed discussions of human rights and ethical approaches to recruitment policy and action that consider global health impacts.</p> <p>Conclusions</p> <p>We suggest that the concept of corporate social responsibility may provide a useful approach at the local organizational level for developing policies on ethical recruitment. Such local policies and subsequent practices may inform public debate on the health equity implications of the HHR flows from poorer to richer countries inherent in the global health worker labour market, which in turn could influence political choices at all government and health system levels.</p

Computational methodology to determine fluid related parameters on non regular three-dimensional scaffolds

The application of three-dimensional (3D) biomaterials to facilitate the adhesion, proliferation, and differentiation of cells has been widely studied for tissue engineering purposes. The fabrication methods used to improve the mechanical response of the scaffold produce complex and non regular structures. Apart from the mechanical aspect, the fluid behavior in the inner part of the scaffold should also be considered. Parameters such as permeability (k) or wall shear stress (WSS) are important aspects in the provision of nutrients, the removal of metabolic waste products or the mechanically-induced differentiation of cells attached in the trabecular network of the scaffolds. Experimental measurements of these parameters are not available in all labs. However, fluid parameters should be known prior to other types of experiments. The present work compares an experimental study with a computational fluid dynamics (CFD) methodology to determine the related fluid parameters (k and WSS) of complex non regular poly(L-lactic acid) scaffolds based only on the treatment of microphotographic images obtained with a microCT (lCT). The CFD analysis shows similar tendencies and results with low relative difference compared to those of the experimental study, for high flow rates. For low flow rates the accuracy of this prediction reduces. The correlation between the computational and experimental results validates the robustness of the proposed methodology.The authors gratefully acknowledge research support from the Spanish Ministry of Science and Innovation through research project DPI2010-20399-C04-01. The Instituto de Salud Carlos III (ISCIII) through the CIBER initiative and the Platform for Biological Tissue Characterization of the Centro de Investigacion Biomedica en Red en Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN) are also gratefully acknowledged.Acosta Santamaría, VA.; Malvé, M.; Duizabo, A.; Mena Tobar, A.; Gallego Ferrer, G.; García Aznar, J.; Doblare Castellano, M.... (2013). Computational methodology to determine fluid related parameters on non regular three-dimensional scaffolds. Annals of Biomedical Engineering. 41(11):2367-2380. https://doi.org/10.1007/s10439-013-0849-8S236723804111Acosta Santamaría, V., H. Deplaine, D. Mariggió, A. R. Villanueva-Molines, J. M. García-Aznar, J. L. Gómez Ribelles, M. Doblaré, G. Gallego Ferrer, and I. Ochoa. Influence of the macro and micro-porous structure on the mechanical behavior of poly(l-lactic acid) scaffolds. J. Non-Cryst. Solids 358(23):3141–3149, 2012.Adachi, T., Y. Osako, M. Tanaka, M. Hojo, and S. J. Hollister. Framework for optimal design of porous scaffold microstructure by computational simulation of bone regeneration. Biomaterials 27(21):3964–3972, 2006.Adamczyk, Z., and T. G. M. Vandeven. Deposition of particles under external forces in laminar-flow through parallel-plate and cylindrical channels. J. Colloid Interface Sci. 80(2):340–356, 1981.Alberich, B. A., D. Moratal, J. L. Escobar, J. C. Rodríguez, A. Vallés-Lluch, L. Martí-Bonmatí, et al. Microcomputed tomography and microfinite element modeling for evaluating polymer scaffolds architecture and their mechanical properties. J. Biomed. Mater. Res. B Appl. Biomater. 91B(1):191–202, 2009.Al-Munajjed, A., M. Hien, R. Kujat, J. P. Gleeson, and J. Hammer. Influence of pore size on tensile strength, permeability and porosity of hyaluronan-collagen scaffolds. J. Mater. Sci. Mater. Med. 19(8):2859–2864, 2008.Alves da Silva, M. L., A. Martins, A. R. Costa-Pinto, V. M. Correlo, P. Sol, M. Bhattacharya, S. Faria, R. L. Reis, and N. M. Neves. Chondrogenic differentiation of human bone marrow mesenchymal stem cells in chitosan-based scaffolds using a flow-perfusion bioreactor. J. Tissue Eng. Regen. Med. 5(9):722–732, 2011.Ansys (2010) CFX Theory User Manual. Canonsburg, PA: Ansys Software.Brígido, R. D., J. M. Estellés, J. A. Sanz, J. M. García-Aznar, and M. S. Sánchez. Polymer scaffolds with interconnected spherical pores and controlled architecture for tissue engineering: fabrication, mechanical properties, and finite element modeling. J. Biomed. Mater. Res. B Appl. Biomater. 81B(2):448–455, 2007.Byrne, P. D., D. Lacroix, J. A. Planell, D. J. Kelly, and P. J. Prendergast. Simulation of tissue differentiation in a scaffold as a function of porosity, Young’s modulus and dissolution rate: application of mechanobiological models in tissue engineering. Biomaterials 28:5544–5554, 2007.Chor, M. V., and W. Li. A permeability measurement system for tissue engineering scaffolds. Meas. Sci. Technol. 18(1):208–216, 2007.Cozensroberts, C., J. A. Quinn, and D. A. Lauffenburger. Receptor-mediated adhesion phenomena—model studies with the radial-flow detachment assay. Biophys. J. 58(1):107–125, 1990.Davisson, T., R. L. Sah, and A. Ratcliffe. Perfusion increases cell content and matrix synthesis in chondrocyte three-dimensional cultures. Tissue Eng. 8(5):807–816, 2002.Deplaine, H., M. Lebourg, P. Ripalda, A. Vidaurre, P. Sanz-Ramos, G. Mora, F. Prósper, I. Ochoa, M. Doblaré, J. L. Gómez Ribelles, I. Izal-Azcárate, and G. Gallego Ferrer. Biomimetic hydroxyapatite coating on pore walls improves osteointegration of poly(l-lactic acid) scaffolds. J. Biomed. Mater. Res. B Appl. Biomater. 101(1):173–186, 2013.Dias, M. R., P. R. Fernandes, J. M. Guedes, and S. J. Hollister. Permeability analysis of scaffolds for bone tissue engineering. J. Biomech. 45(6):938–944, 2012.Freyman, T. M., I. V. Yannas, and L. J. Gibson. Cellular materials as porous scaffolds for tissue engineering. Prog. Mater Sci. 46:273–282, 2001.Gong, S., H. Wang, Q. Sun, S. T. Xue, and J. Wang. Mechanical properties and in vitro biocompatibility of porous zein scaffolds. Biomaterials 27(20):3793–3799, 2006.Gutierrez, R. A., and E. T. Crumpler. Potential effect of geometry on wall shear stress distribution across scaffold surfaces. Ann. Biomed. Eng. 36(1):77–85, 2008.Hammer, D. A., and D. Lauffenburger. A dynamic-model for receptor-mediated cell adhesion to surfaces. Biophys. J. 52(3):475–487, 1987.Ho, S. T., and D. W. Hutmacher. A comparison of micro CT with other techniques used in the characterization of scaffolds. Biomaterials 27(8):1362–1376, 2006.Ho, M. H., P. Y. Kuo, H. J. Hsieh, T. Y. Hsien, L. T. Hou, J. Y. Lai, and D. M. Wang. Preparation of porous scaffolds by using freeze-extraction and freeze-gelation methods. Biomaterials 25(1):129–138, 2004.Hutmacher, D. W., J. T. Schantz, C. X. Lam, K. C. Tan, and T. C. Lim. State of the art and future directions of scaffold-based bone engineering from a biomaterials perspective. J. Tissue Eng. Regen. Med. 1(4):245–260, 2007.Izal, I., P. Aranda, P. Sanz-Ramos, P. Ripalda, G. Mora, F. Granero-Moltó, H. Deplaine, J. L. Gómez-Ribelles, G. G. Ferrer, V. Acosta, I. Ochoa, J. M. García-Aznar, E. J. Andreu, M. Monleón-Pradas, M. Doblaré, and F. Prósper. Culture of human bone marrow-derived mesenchymal stem cells on of poly(l-lactic acid) scaffolds: potential application for the tissue engineering of cartilage. Knee Surg. Sports Traumatol. Arthrosc., 2012.Kapur, S., D. J. Baylink, and K. H. Lau. Fluid flow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways. Bone 32(3):241–251, 2003.Karande, T. S., J. L. Ong, and C. M. Agrawal. Diffusion in musculoskeletal tissue engineering scaffolds: design issues related to porosity, permeability, architecture, and nutrient mixing. Ann. Biomed. Eng. 32(12):1728–1743, 2004.Kelly, D. J., and P. J. Prendergast. Mechano-regulation of stem cell differentiation and tissue regeneration in osteochondral defects. J. Biomech. 38(7):1413–1422, 2005.Kreke, M. R., L. A. Sharp, Y. W. Lee, and A. S. Goldstein. Effect of intermittent shear stress on mechanotransductive signaling and osteoblastic differentiation of bone marrow stromal cells. Tissue Eng. Part A 14(4):529–537, 2008.Lacroix, D., A. Chateau, M. P. Ginebra, and J. A. Planell. Micro-finite element models of bone tissue-engineering scaffolds. Biomaterials 27(30):5326–5334, 2006.Lacroix, D., and P. J. Prendergast. A mechano-regulation model for tissue differentiation during fracture healing: analysis of gap size and loading. J. Biomech. 35(9):1163–1171, 2002.Li, S., J. R. De Wijn, J. Li, P. Layrolle, and K. De Groot. Macroporous biphasic calcium phosphate scaffold with high permeability/porosity ratio. Tissue Eng. 9:535–548, 2003.Melchels, F. P. W., B. Tonnarelli, A. L. Olivares, I. Martin, D. Lacroix, J. Feijen, et al. The influence of the scaffold design on the distribution of adhering cells after perfusion cell seeding. Biomaterials 32(11):2878–2884, 2011.O’Brien, F. J., B. A. Harley, M. A. Waller, I. Yannas, L. J. Gibson, and P. Prendergast. The effect of pore size on permeability and cell attachment in collagen scaffolds for tissue engineering. Technol. Health Care 15(1):3–17, 2007.Ochoa, I., J. A. Sanz, J. M. Garcia-Aznar, M. Doblare, D. M. Yunos, and A. R. Boccaccini. Permeability evaluation of 45S5 bioglass-based scaffolds for bone tissue engineering. J. Biomech. 42:257–260, 2009.Porter, B., R. Zauel, H. Stockman, R. Guldberg, and D. Fyhrie. 3-D computational modeling of media flow through scaffolds in a perfusion bioreactor. Mater. Res. 38:543–549, 2005.Sandino, C., S. Checa, P. J. Prendergast, and D. Lacroix. Simulation of angiogenesis and cell differentiation in a CaP scaffold subjected to compressive strains using a lattice modeling approach. Biomaterials 31(8):2446–2452, 2010.Sanz, J. A., J. M. García-Aznar, and M. Doblaré. On scaffold designing for bone regeneration: a computational multiscale approach. Acta Biomater. 5(1):219–229, 2009.Sanz, J. A., C. Kasper, M. van Griensven, J. M. Garcia-Aznar, I. Ochoa, and M. Doblare. Mechanical and flow characterization of Sponceram® carriers: evaluation by homogenization theory and experimental validation. J. Biomed. Mater. Res. B Appl. Biomater. 87B(1):42–48, 2008.Singh, H., S. H. Teoh, H. T. Low, and D. W. Hutmacher. Flow modelling within a scaffold under the influence of uni-axial and bi-axial bioreactor rotation. J. Biotechnol. 119:181–196, 2005.Sjollema, J., and H. J. Busscher. Deposition of polystyrene latex-particles toward polymethylmethacrylate in a parallel plate flow cell. J. Colloid Interface Sci. 132(2):382–394, 1989.Truscello, S., G. Kerckhofs, S. Van Bael, G. Pyka, J. Schrooten, and H. Van Oosterwyck. Prediction of permeability of regular scaffolds for skeletal tissue engineering: a combined computational and experimental study. Acta Biomater. 8(4):1648–1658, 2012.Woodfield, T. B., J. Malda, J. Wijn, F. Péters, J. Riesle, and C. A. van Blitterswijk. Design of porous scaffolds for cartilage tissue engineering using a three-dimensional fiber-deposition technique. Biomaterials 25(18):4149–4161, 2004

The effects of amisulpride on five dimensions of psychopathology in patients with schizophrenia: a prospective open- label study

BACKGROUND: The efficacy of antipsychotics can be evaluated using the dimensional models of schizophrenic symptoms. The D(2)/D(3)-selective antagonist amisulpride has shown similar efficacy and tolerability to other atypical antipsychotics. The aim of the present study was to determine the efficacy of amisulpride on the dimensional model of schizophrenic symptoms and tolerability in latin schizophrenic patients. METHOD: Eighty schizophrenic patients were enrolled and 70 completed a prospective open-label 3-month study with amisulpride. The schizophrenic symptoms, psychosocial functioning and side-effects were evaluated with standardized scales. RESULTS: The patients showed significant improvement in the five dimensions evaluated. Amisulpride (median final dose 357.1 mg/d) was well-tolerated without treatment-emergent extrapyramidal side-effects. CONCLUSION: Amisulpride showed efficacy on different psychopathological dimensions and was well tolerated, leading to consider this drug a first line choice for the treatment of schizophrenia

Resting state cortico-thalamic-striatal connectivity predicts pesponse to dorsomedial prefrontal rTMS in major depressive disorder

Despite its high toll on society, there has been little recent improvement in treatment efficacy for Major Depressive Disorder (MDD). The identification of biological markers of successful treatment response may allow for more personalized and effective treatment. Here we investigate whether resting state functional connectivity predicted response to treatment with rapid transcranial magnetic stimulation (rTMS) to dorsomedial prefrontal cortex (dmPFC). Twenty five individuals with treatment-refractory MDD underwent a 4-week course of dmPFC-rTMS. Before and after treatment, subjects received resting state functional MRI scans and assessments of depressive symptoms using the Hamilton Depresssion Rating Scale (HAMD17). We found that higher baseline cortico-cortical connectivity (dmPFC-subgenual cingulate and subgenual cingulate to dorsolateral PFC) and lower cortico-thalamic, cortico-striatal and cortico-limbic connectivity were associated with better treatment outcomes. We also investigated how changes in connectivity over the course of treatment related to improvements in HAMD17 scores. We found that successful treatment was associated with increased dmPFC-thalamic connectivity and decreased sgACC-caudate connectivity, Our findings provide insight into which individuals might respond to rTMS treatment and the mechanisms through which these treatments work