An update on the molecular pathology of urinary bladder tumors

Urothelial carcinoma is the fourth most common tumors after prostate cancer, lung, and colorectal carcinoma but the second most common urologic malignancy. Urothelial carcinoma composed more than 90% of bladder tumors while squamous cell carcinoma and adenocarcinomas composed 5% and 2% respectively. The intense research involving the different molecular aspects of bladder cancer has provided a great insight into identifying more about molecular profiling and pathways of bladder cancer.In this review, we will highlight the general concepts of the molecular features; profiling and classification as well as the molecular pathways for bladder carcinomas, especially urothelial carcinoma. Also, we will discuss the advances of molecular biomarkers for screening, early diagnosis, surveillance and potential prognosis of urothelial carcinoma of the bladder. Studies showed that accumulation of genetic alterations involving the clonal expansion of altered cells with growth advantages through sequential multi-step pathways results in progression of bladder tumors.The accumulated research data from literature has revealed that the genomic signatures of urothelial carcinoma are required to subclassify bladder cancer into genetically distinct subgroups. These findings could improve the understating of pathogenesis as well as will provide new therapeutic modules e.g. targeted therapy.     

Ultrasound-Enhanced Protective Effect of Tetramethylpyrazine via the ROS/HIF-1A Signaling Pathway in an in Vitro Cerebral Ischemia/Reperfusion Injury Model

Reactive oxygen species-induced oxidative stress is an important pathophysiological process during cerebral ischemia/reperfusion (I/R) injury. It has been reported that the protective effect of tetramethylpyrazine (TMP) against cerebral I/R injury can be significantly improved by its combination with ultrasound exposure. However, the molecular mechanisms and signaling pathways underlying the synergistic protective effect remain unclear. In the present work, the damage induced by I/R injury was modeled by glutamate-induced toxicity to pheochromocytoma (PC12) cells. The ultrasound-enhanced protective effect of TMP was systemically investigated by measuring variations in cell viability, cell migration and levels of intracellular reactive oxygen species, the oxidative stress-related protein glutathione, apoptosis-related proteins (caspase-8, -9 and -3), as well as expression of related genes (hypoxia-inducible factor-1a, p53, murine double minute2). The results suggest that the ultrasound-enhanced protective effect of TMP against cerebral I/R injury might act via the reactive oxygen species/hypoxia-inducible factor-1a signaling pathway, and an appropriate ultrasound intensity should be selected to achieve an optimal synergistic neuroprotective effect.     

Transduction pathways of GH in ovine mammary acini involving regulated and functional growth hormone receptors

We have investigated the localization and regulation of growth hormone (GH) receptor-related proteins in the ovine mammary gland. Using a new rabbit polyclonal antibody (7122A) directed against the recombinant extracellular domain of GH receptor (GHR-ECD) for western blot assays, we found two bands with apparent molecular weights of 70,000 and 50–60,000?Da in ovine mammary gland solubilized proteins. The 70,000-protein was consistent with a membrane GH receptor form deprived of post-translational modifications such as phosphorylation, glycosylation or ubiquitin binding. The 50–60,000?Da was consistent with soluble GH binding protein, generated by the cleavage of membrane GH receptor. The intensity of related GHR proteins increased slightly throughout mammary gland development and was correlated with the amount of GHR immunoreactivity observed in the mammary gland sections. Moreover, a temporal and spatial regulation of GHR immunoreactivity was found in alveolar epithelial cells. Clearly, marked GHR immunoreactivity was associated with the apical membranes of alveolar epithelial cells at lactation. The up-regulation of related GHR proteins during the differentiation of mammary tissue supports the hypothesis that GH may act specifically via its own receptors. In ovine mammary cells, GH was able to promote a time-dependent activation of MAP kinases such as prolactin (Prl) and placental lactogen (PL). GH was also able to promote slight and transient Stat5 DNA-binding activity. Differences in the time dependence of Stat5 DNA-binding activation by the three different ligands, GH, Prl and PL, were found. All these results emphasize the direct action of GH on ovine mammary cells and highlight the specificity of action of this ligand.     

Disabling inflammatory pathways with biologics and resulting clinical outcomes in severe asthma

Introduction: Patients with severe asthma have a significant unmet need with persistent symptoms and/or frequent exacerbations despite high intensity treatment. These severe unrelenting symptoms have a huge impact on heathcare resources due to frequent hospital admissions and requirement for intensive and expensive medications. There is a compelling need for more effective and safer therapies to help severe asthma sufferers to achieve adequate control of their disease.

Areas covered: Expanding knowledge of innate and adaptive immune responses has led to development of new biologic approaches for severe asthma. Here, the authors will review the existing efficacy and safety data from clinical trials of some of the new biologic therapies that are in development for severe asthma. Their specific role in distinctively targeted subpopulations of severe asthmatics will be also discussed.

Expert opinion: Defining and phenotyping severe asthma patients will become increasingly important as some patients who were previously classified as having severe asthma may become well-controlled with a targeted phenotype-specific treatment. However, pharmacoeconomic concerns should also be taken into account given the elevated acquisition costs of recombinant human monoclonals and of the diagnostic screening procedures for the identification of potential responders.     

Fulfilling the psychological and information need of the family members of critically ill patients using interactive mobile technology: A randomised controlled trial

BackgroundIntensive care nurses may have an important role in empowering families by providing psychological support and fulfilling the family's pivotal need for information.AimTo determine whether ‘education of families by tab’ about the patient’s condition was more associated with improved anxiety, stress, and depression levels than the ‘education of families by routine’.Research designA randomized control trial of 74 main family caregivers (intervention: 39; control: 35).SettingAn adult intensive care unit.Main outcome measuresDepression Anxiety Stress Scale, and Communication and Physical Comfort Scale.ResultsAlthough information need satisfaction was not significantly different between intervention and control groups, the former reported significantly better depression score on Depression Anxiety Stress Scale comparing to the control group (p < 0.01; η² = 0.09) with a medium effect size. Reduction of anxiety in the intervention group were clinically significant.ConclusionThe results suggest that use of ‘education of family by tab’ is promising for intensive care nurses to provide psychological support for family members. More studies are needed to investigate this aspect of family care for better psychological support and information need satisfaction that contributes to the evidence-based practice of intensive care nursing.     

Training police trainees about ways to manage trauma and loss

For the second year we were invited to be trainers at a training seminar for senior police educators, held in the German Federal Police University and sponsored by the European Police College, hence, having the opportunity to build on their previous applications. We applied exercises (psychoeducation, mindfulness/awareness, journaling, processing in dyads) that introduced in this training and designed to teach officers how to handle exposure to adversities and minimize potential negative consequences. Police officers expect exposure to potentially traumatic incidents, yet, often suffer deeply because of unresolved trauma related to handling horrific events. Our work aimed to open discussion in order to formulate a standard component in training curricula related to teaching police trainees ways to effectively handle and process trauma.     

专科护士培训体验式教学理论模型的构建

目的 构建重症医学专科护士培训体验式教学理论模型.方法 以贵州省重症医学专科护士培训教学活动为基础,采用文献分析法、问卷调查法、实证研究法、经验总结法,研究重症医学专科护士培训体验式教学理论模型.结果 构建了包括四内容(教学目标、教学内容、教学形式、教学评价),四环节(危重患者护理体验、反思与分享、感悟内化、实践与应用)、三过程(基础、提高、升华)的循环上升式重症医学专科护士培训体验式教学理论模型.结论该理论模型展现了重症医学专科护士培训体验式教学的规律,为专科护士培养提供优化的教学途径.