Genes and miRNAs as Hurdles and Promoters of Corticospinal Tract Regeneration in Spinal Cord Injury

Spinal cord injury (SCI) is a devastating lesion to the spinal cord, which determines the interruption of ascending/descending axonal tracts, the loss of supraspinal control of sensory-motor functions below the injured site, and severe autonomic dysfunctions, dramatically impacting the quality of life of the patients. After the acute inflammatory phase, the progressive formation of the astrocytic glial scar characterizes the acute-chronic phase: such scar represents one of the main obstacles to the axonal regeneration that, as known, is very limited in the central nervous system (CNS). Unfortunately, a cure for SCI is still lacking: the current clinical approaches are mainly based on early vertebral column stabilization, anti-inflammatory drug administration, and rehabilitation programs. However, new experimental therapeutic strategies are under investigation, one of which is to stimulate axonal regrowth and bypass the glial scar. One major issue in axonal regrowth consists of the different genetic programs, which characterize axonal development and maturation. Here, we will review the main hurdles that in adulthood limit axonal regeneration after SCI, describing the key genes, transcription factors, and miRNAs involved in these processes (seen their reciprocal influencing action), with particular attention to corticospinal motor neurons located in the sensory-motor cortex and subjected to axotomy in case of SCI. We will highlight the functional complexity of the neural regeneration programs. We will also discuss if specific axon growth programs, that undergo a physiological downregulation during CNS development, could be reactivated after a spinal cord trauma to sustain regrowth, representing a new potential therapeutic approach

Analysis of navigation pattern in the sport of rowing

The effect of weather and environmental conditions on sports has been extensively studied over the last few years (Pezzoli et al., 2010). Based upon the studies of Lobozewicz (1981) and of Kay and Vamplew (2002), Pezzoli and Cristofori (2008) have studied the impact of some specific environmental parameters over different sports using a particular impact index divided into five classes. This analysis clearly shows that most of the outdoor sport activities are strongly influenced by the variation of meteorological parameters. However the impact of meteorological conditions on outdoor sport activities has not yet been extensively studied. The aim of this research is to show that an accurate assessment of wind and wave parameters enables decisive improvements in both training and race strategy planning. Furthermore this analysis provide a very innovative working method for the applied sport research. The work has been based on in-situ measurements of both environmental and performance parameters (wind direction, wind velocity, boat speed and stroke rate) made over different classes and in different race conditions during the 2009 FISA World Championship (Poznan, Poland). In particular a detailed environmental analysis was performed by measuring the wind direction, the wind speed and by evaluating the significant wave height and the wave peak period for each class during the semi-final phase and the final phase. It should be noted that, since wind is a key parameter affecting not only the boat speed but also the race strategy, the assessment of the wind velocity and of the wind direction has been made in connection with the boat movement. The comparison between coupled wind-wave data, boat speed and stroke rate evidently demonstrates that only crews that managed the adaption to changing in the environmental conditions from semi-final to final phase of the race, were able to get better results. References Kay, J., & Vamplew, W. (2002) Weather beaten: sport in the British climate. London: Ed. Mainstream Publishing. Lobozewicz, T. (1981) Meteorology in sport. Frankfurt: Ed. Sportverlag. Pezzoli, A,, Moncalero, M., Boscolo, A., Cristofori, E., Giacometto, F., Gastaldi, S., & Vercelli, G. (2010) The meteo-hydrological analysis and the sport performance: which are the connections? The case of the XXI Winter Olympic Games, Vancouver 2010, Journal of Sports Medicine and Physical Fitness, 50: 19-20. Pezzoli, A., & Cristofori, E. (2008) Analisi, previsioni e misure meteorologiche applicate agli sport equestri, in: 10th Congress "New findings in equine practices, Druento: Centro Internazionale del Cavallo Ed., p.38-4

A wide difference in cancer survival between middle aged and elderly patients in Europe.

Abstract Nowadays the burden of cancer in elderly people has reached an alarming extent. The purpose of this study is comparing cumulative and conditional relative survival in elderly patients between 65 and 84 years and younger adults aged from 55 to 64. Fifty-three cancer registries of 22 European countries, participating in the EUROCARE-3 programme, collected information on the cases diagnosed over the period 1990-1994. We computed cumulative and conditional relative survival for 16 cancer sites. Middle aged patients experienced a better prognosis than the elderly for all cancer sites, in both sexes and the differences were more marked at 1 than 5 years since diagnosis. The very large differences noted in the first period after cancer detection declined in the subsequent years and, when 5-years conditional survival was considered, for several cancers the elderly and younger adults had the same probabilities of surviving. The death relative excess risks (RERs) in the elderly with respect younger individuals were really very high and markedly larger at 1 than 5 years, and in women than men. Genitourinary and gynaecological cancers showed the highest RERs, around 2.0 and between 1.5 and 2.5 respectively. This very high early mortality could be due not only to clinical aspects: the barriers to health care access and a consequent late diagnosis might represent for elderly patients the main determinant of this very large prognostic disadvantage. In conclusion, clinical management of cancer in the elderly remains a major issue to be faced with complex social and health care policies

Increasing agrin function antagonizes muscle atrophy and motor impairment in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a pediatric genetic disease, characterized by motor neuron (MN) death, leading to progressive muscle weakness, respiratory failure, and, in the most severe cases, to death. Abnormalities at the neuromuscular junction (NMJ) have been reported in SMA, including neurofilament (NF) accumulation at presynaptic terminals, immature and smaller than normal endplates, reduced transmitter release, and, finally, muscle denervation. Here we have studied the role of agrin in SMAΔ7 mice, the experimental model of SMAII. We observed a 50% reduction in agrin expression levels in quadriceps of P10 SMA mice compared to age-matched WT controls. To counteract such condition, we treated SMA mice from birth onwards with therapeutic agrin biological NT-1654, an active splice variant of agrin retaining synaptogenic properties, which is also resistant to proteolytic cleavage by neurotrypsin. Mice were analyzed for behavior, muscle and NMJ histology, and survival. Motor behavior was significantly improved and survival was extended by treatment of SMA mice with NT-1654. At P10, H/E-stained sections of the quadriceps, a proximal muscle early involved in SMA, showed that NT-1654 treatment strongly prevented the size decrease of muscle fibers. Studies of NMJ morphology on whole-mount diaphragm preparations revealed that NT-1654-treated SMA mice had more mature NMJs and reduced NF accumulation, compared to vehicle-treated SMA mice. We conclude that increasing agrin function in SMA has beneficial outcomes on muscle fibers and NMJs as the agrin biological NT-1654 restores the crosstalk between muscle and MNs, delaying muscular atrophy, improving motor performance and extending survival

Penentuan Lembaga Credit Union sebagai Subjek Pajak Penghasilan Atas Penghasilan dari USAha yang Diterima atau Diperoleh Wajib Pajak yang Memiliki Peredaran Bruto Tertentu ( Studi Kasus pada Kantor Pusat Credit Union Keling Kumang \Tapang Sambas di Kabupa

This thesis discusses the determination of the institution as a credit union subject to tax based on Government Regulation No. 46 of 2013 challenged about income tax on income from businesses that received or acquired by a taxpayer who has a gross turnover of a particular (case study on credit union headquarters rivet kumang Sambas district Tapang Sekadau). Indonesian state categorized as a modern constitutional state (moderne rechtsstaat) or patterned welfare state (welvaarstaat; wohlfahrtsstaat) - aimed at the realization of a just and prosperous society that are materially and spiritually. To organize the people's welfare, taxes as a source of funds very central role in meeting the needs of the budget. One of the types of taxes that exist in Indonesia are Income Tax (VAT). The imposition of income tax is based on two conditions, namely taxes and subject to tax. In other words, to truly become a taxpayer, should qualify the subjective and objective conditions. Subject can only be subject to income tax tax if the income tax is no object. The applicable tax rate in Indonesia adheres to the principle of taxation of income in the broad sense, which includes all the income or economic capability acquired additional taxpayer, wherever arising, and any shape and its name, to the extent it can be used for consumption or increase wealth. Basically adhere to the Income Tax Act on the basis of net taxation (net bases of taxation) to the taxpayer in the country. That the basis for determining the Credit Union As a tax subject. Cooperatives and Small and Medium Enterprises (MSME) as productive businesses that have an income, quantitatively to contribute to national and regional economies. To provide convenience to the taxpayer of MSME, Government of the Republic of Indonesia issued Government Regulation (PP) No. 46 Year 2013 on income tax on income from businesses that received or acquired by a taxpayer who has a certain gross turnover. During this time, KUMKM encountered problems with the tax calculation procedures that must be paid in accordance Article 29 Income taxation on the cooperative is generally a collection of low-income community members still causing the pros and cons in various circles. Moreover, the imposition of final tax imposed on the cooperative efforts of the turnover or circulation of less than Rp.4,8 billion a year, instead of the value as income tax bases in general. Aspect of justice is the main criticism of the application of the concept to final taxation ini.Kendala juridical and technical implementation of the CU rivet Kumang Tapang Sambas as one subject to tax under Regulation 46 of 2013 the Juridical Obstacles related to overlapping rules, which is considered the final income tax unfair imposition Final Income Tax Policy towards SMEs backward and not aligned with the main purpose of the system of self - assessment, there are those who benefit and some are harmed and the existence of mechanisms Exemption Certificate (LCS). While constraints are teknisya How to calculate the imposition of tax and How to Deposit and reporting that is still not understood by CU Rivet Kumang.

Mesenchymal Stem Cells for Spinal Cord Injury: Current Options, Limitations, and Future of Cell Therapy

Spinal cord injury (SCI) constitutes an inestimable public health issue. The most crucial phase in the pathophysiological process of SCI concerns the well-known secondary injury, which is the uncontrolled and destructive cascade occurring later with aberrant molecular signaling, inflammation, vascular changes, and secondary cellular dysfunctions. The use of mesenchymal stem cells (MSCs) represents one of the most important and promising tested strategies. Their appeal, among the other sources and types of stem cells, increased because of their ease of isolation/preservation and their properties. Nevertheless, encouraging promise from preclinical studies was followed by weak and conflicting results in clinical trials. In this review, the therapeutic role of MSCs is discussed, together with their properties, application, limitations, and future perspectives