\u3ci\u3eMedicine Meets Virtual Reality 16\u3c/i\u3e

Chapter, Validating Advanced Robot-Assisted Laparoscopic Training Task in Virtual Reality, co-authored by Nicholas Stergiou, UNO faculty member. We humans are tribal, grouping ourselves by a multitude of criteria: physical, intellectual, political, emotional, etc. The Internet and its auxiliary technologies have enabled a novel dimension in tribal behavior during our recent past. This growing connectivity begs the question: will individuals and their communities come together to solve some very urgent global problems? At MMVR, we explore ways to harness information technology to solve healthcare problems – and in the industrialized nations we are making progress. In the developing world however, things are more challenging. Massive urban poverty fuels violence and misery. Will global networking bring a convergence of individual and tribal problem-solving? Recently, a barrel-shaped water carrier that rolls along the ground was presented, improving daily life for many people. Also the One Laptop per Child project is a good example of how the industrialized nations can help the developing countries. They produce durable and simple laptops which are inexpensive to produce. At MMVR, we focus on cutting-edge medical technology, which is generally pretty expensive. While the benefits of innovation trickle downward, from the privileged few to the broader masses, we should expand this trickle into a flood. Can breakthrough applications in stimulation, visualization, robotics, and informatics engender tools as ingeniously as the water carrier or laptop? With some extra creativity, we can design better healthcare for the developing world too.https://digitalcommons.unomaha.edu/facultybooks/1234/thumbnail.jp

Nitric Oxide Induces Cell Death by Regulating Anti-Apoptotic BCL-2 Family Members

Nitric oxide (NO) activates the intrinsic apoptotic pathway to induce cell death. However, the mechanism by which this pathway is activated in cells exposed to NO is not known. Here we report that BAX and BAK are activated by NO and that cytochrome c is released from the mitochondria. Cells deficient in Bax and Bak or Caspase-9 are completely protected from NO-induced cell death. The individual loss of the BH3-only proteins, Bim, Bid, Puma, Bad or Noxa, or Bid knockdown in Bim−/−/Puma−/− MEFs, does not prevent NO-induced cell death. Our data show that the anti-apoptotic protein MCL-1 undergoes ASK1-JNK1 mediated degradation upon exposure to NO, and that cells deficient in either Ask1 or Jnk1 are protected against NO-induced cell death. NO can inhibit the mitochondrial electron transport chain resulting in an increase in superoxide generation and peroxynitrite formation. However, scavengers of ROS or peroxynitrite do not prevent NO-induced cell death. Collectively, these data indicate that NO degrades MCL-1 through the ASK1-JNK1 axis to induce BAX/BAK-dependent cell death

Protein kinase C and cardiac dysfunction: a review

Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure

Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation

Acetylcholine (ACh) has been shown to modulate neuronal differentiation during early development. Both muscarinic and nicotinic acetylcholine receptors (AChRs) regulate a wide variety of physiological responses, including apoptosis, cellular proliferation and neuronal differentiation. However, the intracellular mechanisms underlying these effects of AChR signaling are not fully understood. It is known that activation of AChRs increase cellular proliferation and neurogenesis and that regulation of intracellular calcium through AChRs may underlie the many functions of ACh. Intriguingly, activation of diverse signaling molecules such as Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, protein kinase C and c-Src is modulated by AChRs. Here we discuss the roles of ACh in neuronal differentiation, cell proliferation and apoptosis. We also discuss the pathways involved in these processes, as well as the effects of novel endogenous AChRs agonists and strategies to enhance neuronal-differentiation of stem and neural progenitor cells. Further understanding of the intracellular mechanisms underlying AChR signaling may provide insights for novel therapeutic strategies, as abnormal AChR activity is present in many diseases

Validated robotic laparoscopic surgical training in a virtual-reality environment

BackgroundA robotic virtual-reality (VR) simulator has been developed to improve robot-assisted training for laparoscopic surgery and to enhance surgical performance in laparoscopic skills. The simulated VR training environment provides an effective approach to evaluate and improve surgical performance. This study presents our findings of the VR training environment for robotic laparoscopy. Methods Eight volunteers performed two inanimate tasks in both the VR and the actual training environment. The tasks were bimanual carrying (BC) and needle passing (NP). For the BC task, the volunteers simultaneously transferred two plastic pieces in opposite directions five times consecutively. The same volunteers passed a surgical needle through six pairs of holes in the NP task. Both tasks require significant bimanual coordination that mimics actual laparoscopic skills. Data analysis included time to task completion, speed and distance traveled of the instrument tip, as well as range of motion of the subject’s wrist and elbow of the right arm. Electromyography of the right wrist flexor and extensor were also analyzed. Paired t-tests and Pearson’s r were used to explore the differences and correlations between the two environments. Results There were no significant differences between the actual and the simulated VR environment with respect to the BC task, while there were significant differences in almost all dependent parameters for the NP task. Moderate to high correlations for most dependent parameters were revealed for both tasks. Conclusions Our data shows that the VR environment adequately simulated the BC task. The significant differences found for the NP task may be attributed to an oversimplification in the VR environment. However, they do point to the need for improvements in the complexity of our VR simulation. Further research work is needed to develop effective and reliable VR environments for robotic laparoscopic training

Adrenergic receptor stimulation of the mitogen-activated protein kinase cascade and cardiac hypertrophy.

Phenylephrine and noradrenaline (alpha-adrenergic agonism) or isoprenaline (beta-adrenergic agonism) stimulated protein synthesis rates, increased the activity of the atrial natriuretic factor gene promoter and activated mitogen-activated protein kinase (MAPK). The EC50 for MAPK activation by noradrenaline was 2-4 microM and that for isoprenaline was 0.2-0.3 microM. Maximal activation of MAPK by isoprenaline was inhibited by the beta-adrenergic antagonist, propranolol, whereas the activation by noradrenaline was inhibited by the alpha1-adrenergic antagonist, prazosin. FPLC on a Mono-Q column separated two peaks of MAPK (p42MAPK and p44MAPK) and two peaks of MAPK-activating activity (MEK) activated by isoprenaline or noradrenaline. Prolonged phorbol ester exposure partially down-regulated the activation of MAPK by noradrenaline but not by isoprenaline. This implies a role for protein kinase C in MAPK activation by noradrenaline but not isoprenaline. A role for cyclic AMP in activation of the MAPK pathway was eliminated when other agonists that elevate cyclic AMP in the cardiac myocyte did not activate MAPK. In contrast, MAPK was activated by exposure to ionomycin, Bay K8644 or thapsigargin that elevate intracellular Ca2+. Furthermore, depletion of extracellular Ca2+ concentrations with bis-(o-aminophenoxy)ethane-NNN'N'-tetra-acetic acid (BAPTA) or blocking of the L-type Ca2+ channel with nifepidine or verapamil inhibited the response to isoprenaline without inhibiting the responses to noradrenaline. We conclude that alpha- and beta-adrenergic agonists can activate the MEK/MAPK pathway in the heart by different signalling pathways. Elevation of intracellular Ca2+ rather than cyclic AMP appears important in the activation of MAPK by isoprenaline in the cardiac myocyte