Sprouty proteins are evolutionarily conserved modulators of MAPK/ERK pathway. Through interacting with an increasing number of effectors, mediators, and regulators with ultimate influence on multiple targets within or beyond ERK, Sprouty orchestrates a complex, multilayered regulatory system and mediates a crosstalk among different signaling pathways for a coordinated cellular response. As such, Sprouty has been implicated in various developmental and physiological processes. Evidence shows that ERK is aberrantly activated in malignant conditions. Accordingly, Sprouty deregulation has been reported in different cancer types and shown to impact cancer development, progression, and metastasis. In this article, we have tried to provide an overview of the current knowledge about the Sprouty physiology and its regulatory functions in health, as well as an updated review of the Sprouty status in cancer. Putative implications of Sprouty in cancer biology, their clinical relevance, and their proposed applications are also revisited. As a developing story, however, role of Sprouty in cancer remains to be further elucidated.

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Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis which drives endothelial cell survival, proliferation, and migration while increasing vascular permeability. Playing an important role in the physiology of normal ovaries, VEGF has also been implicated in the pathogenesis of ovarian cancer. Essentially by promoting tumor angiogenesis and enhancing vascular permeability, VEGF contributes to the development of peritoneal carcinomatosis associated with malignant ascites formation, the characteristic feature of advanced ovarian cancer at diagnosis. In both experimental and clinical studies, VEGF levels have been inversely correlated with survival. Moreover, VEGF inhibition has been shown to inhibit tumor growth and ascites production and to suppress tumor invasion and metastasis. These findings have laid the basis for the clinical evaluation of agents targeting VEGF signaling pathway in patients with ovarian cancer. In this review, we will focus on VEGF involvement in the pathophysiology of ovarian cancer and its contribution to the disease progression and dissemination.

Pseudomyxoma peritonei (PMP, ORPHA26790) is a clinical syndrome characterized by progressive dissemination of mucinous tumors and mucinous ascites in the abdomen and pelvis. PMP is a rare disease with an estimated incidence of 1–2 out of a million. Clinically, PMP usually presents with a variety of unspecific signs and symptoms, including abdominal pain and distention, ascites or even bowel obstruction. It is also diagnosed incidentally at surgical or non-surgical investigations of the abdominopelvic viscera. PMP is a neoplastic disease originating from a primary mucinous tumor of the appendix with a distinctive pattern of the peritoneal spread. Computed tomography and histopathology are the most reliable diagnostic modalities. The differential diagnosis of the disease includes secondary peritoneal carcinomatoses and some rare peritoneal conditions. Optimal elimination of mucin and the mucin-secreting tumor comprises the current standard of care for PMP offered in specialized centers as visceral resections and peritonectomy combined with intraperitoneal chemotherapy. This multidisciplinary approach has reportedly provided a median survival rate of 16.3 years, a median progression-free survival rate of 8.2 years and 10- and 15-year survival rates of 63% and 59%, respectively. Despite its indolent, bland nature as a neoplasm, PMP is a debilitating condition that severely impacts quality of life. It tends to be diagnosed at advanced stages and frequently recurs after treatment. Being ignored in research, however, PMP remains a challenging, enigmatic entity. Clinicopathological features of the PMP syndrome and its morbid complications closely correspond with the multifocal distribution of the secreted mucin collections and mucin-secreting implants. Novel strategies are thus required to facilitate macroscopic, as well as microscopic, elimination of mucin and its source as the key components of the disease. In this regard, MUC2, MUC5AC and MUC5B have been found as the secreted mucins of relevance in PMP. Development of mucin-targeted therapies could be a promising avenue for future research which is addressed in this article.

Sustained voltammetric responses, with periods 2-12 times longer than the period of the cycling potential, were found in application of cyclic voltammetry to the oxidation of methanol at a rotating platinum disk in alkaline solution. Experiments were conducted in which a control parameter (the upper potential limit of the potential cycle) was varied. The results demonstrate that the periodic states are ordered in the same way as dynamical states with the same symbolic representations are ordered in a combined forward and reverse U-sequence. Between ranges of the bifurcation parameter for which periodic states were observed, aperiodic behavior was found that possessed properties that are characteristic of deterministic chaos. High-order periodic responses were also obtained in experiments in which the system was allowed to relax under fixed conditions following the transfer of the Pt electrode to the methanol solution. These results provide evidence that the high-order periodic states do not arise from a slow aging process but, instead, are a consequence of the electrochemical mechanism for the voltammetric oxidation of methanol.

BackgroundPatients who receive care in an emergency department (ED), are usually unattended while waiting in queues.ObjectivesThis study was done to determine, whether the application of queuing theory analysis might shorten the waiting times of patients admitted to emergency wards.Patients and MethodsThis was an operational study to use queuing theory analysis in the ED. In the first phase, a field study was conducted to delineate the performance of the ED and enter the data obtained into simulator software. In the second phase, "ARENA" software was used for modeling, analysis, creating a simulation and improving the movement of patients in the ED. Validity of the model was confirmed through comparison of the results with the real data using the same instrument. The third phase of the study concerned modeling in order to assess the effect of various operational strategies, on the queue waiting time of patients who were receiving care in the ED.ResultsIn the first phase, it was shown that 47.7% of the 3000 patient records were cases referred for trauma treatment, and the remaining 52.3% were referred for non-trauma services. A total of 56% of the cases were male and 44% female. Maximum input was 4.5 patients per hour and the minimum input was 0.5 per hour. The average length of stay for patients in the trauma section was three hours, while for the non-trauma section it was four hours. In the second phase, modeling was tested with common scenarios. In the third phase, the scenario with the addition of one or more senior emergency resident(s) on each shift resulted in a decreased length of stay from 4 to 3.75 hours. Moreover, the addition of one bed to the Intensive Care Unit (ICU) and/or Critical Care Unit (CCU) in the study hospital, reduced the occupancy rate of the nursing service from 76% to 67%. By adding another clerk to take electrocardiograms (ECG) in the ED, the average time from a request to performing the procedure is reduced from 26 to 18 minutes. Furthermore, the addition of 50% more staff to the laboratory and specialist consultations led to a 90 minute reduction in the length of stay. It was also shown that earlier consultations had no effect on the length of stay.ConclusionsApplication of queuing theory analysis can improve movement and reduce the waiting times of patients in bottlenecks within the ED throughput.

The changes in behavior that lead to a period-doubling bifurcation were investigated in the application of cyclic voltammetry to the oxidation of methanol at a rotating platinum disk electrode in alkaline solution.Two parameters were separately varied, the concentration of methanol and the upper potential limit of the potential cycle. Feedback mechanisms that explain the changes in behavior are formulated from experimental data and an electrochemical mechanism. Evidence is presented that indicates a period-two cyclic voltammogram occurs due to the dual role played by the surface species PtOH. During one cycle of the period-two response, most of the PtOH that forms on the surface reacts with an intermediate of methanol oxidation. During the other cycle a substantial amount of PtOH is transformed to Pt oxides. A Mobius strip that formed before the period-doubling bifurcation was detected by examining current-potential curves. Near the point in parameter space where the Mobius strip formed the relaxation was fastest.

Neither nitrous oxide/oxygen or fentanyl appeared to be superior to the other in relieving moderate to severe pain among emergency patients presenting with isolated limb fracture or dislocation. In an ED, increased use of nitrous oxide might reduce the overall need for opiate analgesia, and in our setting, the need for constant monitoring.