Investigation of Effects of L-Theanine on PTSD-induced Changes in Rat Neurobehavior

Post-traumatic stress disorder (PTSD) is a devastating neuropsychological disorder that may develop in response to traumatic experiences. Symptoms include anxiety, hypervigilance, memory deficits, and depression. We investigated L-Theanine on neurobehavioral effects in a PTSD rodent model. Evaluation of the effects of L-Theanine as a sole agent and in combination with midazolam on neurobehavior was analyzed using the Elevated Plus-Maze, Morris Water Maze, and Forced Swim Test. Statistical analysis consisted of comparison of PTSD symptoms in PTSD vs. non-stressed groups. Data regarding weight gain between the 40 control (non-stressed) and 40 PTSD (stressed) rats were significantly different (p < 0.001), where the control rats gained an average of 55.4 grams compared to 37.4 grams for the PTSD rats over the 10 post stress days. This research did not show statistical significance with single dose administration of L-Theanine or in combination with midazolam. However, the theoretic framework and Post-Traumatic Stress Disease Induction Model were validated based on this research. This study establishes a solid framework for future investigation of PTSD treatments. Future studies of L-Theanine and other herbal therapies may use an extended dosing period to obtain a steady state for the period of time needed to alter neurobiology

DNA-PKcs-Mediated Transcriptional Regulation Drives Prostate Cancer Progression and Metastasis.

Emerging evidence demonstrates that the DNA repair kinase DNA-PKcs exerts divergent roles in transcriptional regulation of unsolved consequence. Here, in vitro and in vivo interrogation demonstrate that DNA-PKcs functions as a selective modulator of transcriptional networks that induce cell migration, invasion, and metastasis. Accordingly, suppression of DNA-PKcs inhibits tumor metastases. Clinical assessment revealed that DNA-PKcs is significantly elevated in advanced disease and independently predicts for metastases, recurrence, and reduced overall survival. Further investigation demonstrated that DNA-PKcs in advanced tumors is highly activated, independent of DNA damage indicators. Combined, these findings reveal unexpected DNA-PKcs functions, identify DNA-PKcs as a potent driver of tumor progression and metastases, and nominate DNA-PKcs as a therapeutic target for advanced malignancies

Free Labour, Social Media, Management: Challenging Marxist Organization Studies

In this paper we explore how so-called ‘social media’ such as Facebook challenge Marxist organization studies. We argue that understanding the role of user activity in web 2.0 business models requires a focus on ‘work’, understood as value productive activity, that takes place beyond waged labour in the firm. A reading of Marx on the socialization of labour highlights the emerging figure of ‘free labour’, which is both unpaid and uncoerced. Marxist work on the production of the ‘audience commodity’ provides one avenue for understanding the production of content and data by users as free labour, but this raises questions concerning the distinction between productive and unproductive labour, which is central to Marx’s labour theory of value. The Marxist literature on ‘the becoming rent of profit’ allows for a partial understanding of how the value produced by free labour is captured, thereby developing the understanding of the economic dimension of ‘free labour’ as unpaid. It overstates, however, the ‘uncontrolled’ side of free labour, and neglects the ways in which this work is managed so as to ensure that it is productive. We therefore call for a return to Marxist labour process analysis, albeit with an expanded focus on labour and a revised understanding of control associated with digital protocols. On this basis, a Marxist organization studies can contribute to an understanding of the political economy of digital capitalism

Orthoxenografts of testicular germ cell tumors demonstrate genomic changes associated with cisplatin resistance and identify PDMP as a resensitizing agent

[Purpose] To investigate the genetic basis of cisplatin resistance as efficacy of cisplatin-based chemotherapy in the treatment of distinct malignancies is often hampered by intrinsic or acquired drug resistance of tumor cells.[Experimental Design] We produced 14 orthoxenograft transplanting human nonseminomatous testicular germ cell tumors (TGCT) in mice, keeping the primary tumor features in terms of genotype, phenotype, and sensitivity to cisplatin. Chromosomal and genetic alterations were evaluated in matched cisplatin-sensitive and their counterpart orthoxenografts that developed resistance to cisplatin in nude mice.[Results] Comparative genomic hybridization analyses of four matched orthoxenografts identified recurrent chromosomal rearrangements across cisplatin-resistant tumors in three of them, showing gains at 9q32-q33.1 region. We found a clinical correlation between the presence of 9q32-q33.1 gains in cisplatin-refractory patients and poorer overall survival (OS) in metastatic germ cell tumors. We studied the expression profile of the 60 genes located at that genomic region. POLE3 and AKNA were the only two genes deregulated in resistant tumors harboring the 9q32-q33.1 gain. Moreover, other four genes (GCS, ZNF883, CTR1, and FLJ31713) were deregulated in all five resistant tumors independently of the 9q32-q33.1 amplification. RT-PCRs in tumors and functional analyses in Caenorhabditis elegans (C. elegans) indicate that the influence of 9q32-q33.1 genes in cisplatin resistance can be driven by either up- or downregulation. We focused on glucosylceramide synthase (GCS) to demonstrate that the GCS inhibitor DL-threo-PDMP resensitizes cisplatin-resistant germline-derived orthoxenografts to cisplatin[Conclusions] Orthoxenografts can be used preclinically not only to test the efficiency of drugs but also to identify prognosis markers and gene alterations acting as drivers of the acquired cisplatin resistance.Several authors are grateful recipients of predoctoral fellowships: J.M. Piulats from the AECC and F.J. García-Rodríguez from the Instituto de Salud Carlos III (ISCIII). This study was supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2002-02265 and FIS: BFU2007-67123; PI10-0222, PI13-01339, and PI16/01898, to A. Villanueva; PI15-00895, to J. Ceron; SAF2013-46063R, to F. Vi nals; PI030264, to ~ X. García-del-Muro), Fundacio La Marat o TV3 (051430, to F. Vi nals and X. ~ García-del-Muro), Generalitat de Catalunya (2014SGR364, to A. Villanueva and F. Vinals; FIS09/0059, to A. Morales), cofunded by FEDER funds/ ~ European Regional Development Fund (ERDF) — a way to Build Europe. A. Villanueva received a BAE11/00073 grant. We thank the staff of the Animal Core Facility of IDIBELL for mouse care and maintenance.Peer reviewe

Enterocolitis necrotizante en recién nacidos ingresados en el Servicio de Neonatología del Hospital Escuela "Carlos Roberto Huembes" en el período comprendido de Enero 2011 a Diciembre 2013

La enterocolitis necrotizante en el recién nacido presenta un amplio espectro de manifestaciones clínicas, caracterizándose principalmente por la tríada de distensión abdominal, sangramiento gastrointestinal y neumatosis intestinal. A pesar del avance en el cuidado intensivo neonatal, persiste como una enfermedad grave, que afecta habitualmente al recién nacido pretérmino, especialmente de muy bajo peso

Drug discovery in advanced prostate cancer: translating biology into therapy.

Castration-resistant prostate cancer (CRPC) is associated with a poor prognosis and poses considerable therapeutic challenges. Recent genetic and technological advances have provided insights into prostate cancer biology and have enabled the identification of novel drug targets and potent molecularly targeted therapeutics for this disease. In this article, we review recent advances in prostate cancer target identification for drug discovery and discuss their promise and associated challenges. We review the evolving therapeutic landscape of CRPC and discuss issues associated with precision medicine as well as challenges encountered with immunotherapy for this disease. Finally, we envision the future management of CRPC, highlighting the use of circulating biomarkers and modern clinical trial designs