Beneficial effect of Sparassis crispa on stroke through activation of Akt/eNOS pathway in brain of SHRSP

Sparassis crispa (S. crispa) is a mushroom used as a natural medicine that recently became cultivatable in Japan. In this study, we investigated not only the preventive effects of S. crispa against stroke and hypertension in stroke-prone spontaneously hypertensive rats (SHRSP) but also the mechanism involved by using studies of the cerebral cortex at a young age. Six-week-old male SHRSP were divided into 2 groups, a control group and an S. crispa group administered 1.5% S. crispa in feed, and we then observed their survival. In addition, rats of the same age were treated with 1.5% S. crispa for 4 weeks and we measured body weight, blood pressure, blood flow from the tail, NOx production, and the levels of expression of several proteins in the cerebral cortex by western blot analysis. Our results showed that the S. crispa group had a delayed incidence of stroke and death and significantly decreased blood pressure and increased blood flow after the administration. Moreover, the quantity of urinary excretion and the nitrate/nitrite concentration in cerebral tissue were higher than those of control SHRSP rats. In the cerebral cortex, phosphor-eNOS (Ser1177) and phosphor-Akt (Ser473) in S. crispa-treated SHRSP were increased compared with those of control SHRSP rats. In conclusion, S. crispa could ameliorate cerebrovascular endothelial dysfunction by promoting recovery of Akt-dependent eNOS phosphorylation and increasing NO production in the cerebral cortex. S. crispa may be useful for preventing stroke and hypertension

Evaluation of Essential and Toxic Elements in Blood Samples of Male Smokers Having Different Types of Cancers with Reference to Healthy Male Smokers

Immense epidemiologic studies have been reported about the role of essential trace and toxic elements as risk factors for incidence of different type of cancers in population of developed and developing countries. In present work the levels of carcinogenic, Arsenic, Cadmium, and Nickel (As, Cd and Ni) and anti-carcinogenic, Zinc and Selenium (Zn and Se) elements were measured in blood of male cancer patients (urinary bladder, lung, mouth and esophageal) and healthy referents. The all patients and referents were smoker. The blood samples were analysed with atomic absorption spectrometry after microwave assisted acid digestion. The resulted data indicated that the levels of toxic elements As, Ni and Cd were considerably elevated whereas essential elements, Zn and Se were lower in blood samples of all cancer cases as compared to those values found in noncancerous subjects. As the levels of essential trace elements were low in blood samples of male cancerous patients but difference was highly significant in lung and mouth cancer subjects (p<0.001), whereas sequence of decreasing order was not uniform. The levels of Zn in blood samples of different cancerous patients were found in decreasing order as: esophagus< mouth< urinary bladder<lung, whereas in case of Se as mouth<lung<urinary bladder<esophagus.The study revealed that the carcinogenic processes are significantly affecting the essential and toxic elements levels in biological samples of cancerous patients as related to those obtained for controls/referents

Strategic Research Alliance Final Report : Review of Continuing Professional Development in Nursing

Continuing Professional Development (CPD) is important in generating and sustaining capability and in ensuring high quality, person-centred, safe and effective nursing care. In the UK, changes to models of funding for nursing CPD have raised concerns about the opportunities available for nurses to meet the requirements for revalidation of registration, their ability to provide adequate supervision of future students in relation to the new NMC standards of proficiency, and the potential impact of reductions in CPD access to nursing recruitment and retention. Contemporary evidence suggests that it is not only the opportunity to access CPD that is important to the provision of quality care, but also the ability to transform knowledge and skills learnt into practice within diverse practice settings. The purpose of CPD therefore is not only transformation of an individual’s practice but also transformation of workplace culture and context. For the purpose of this report, we follow Manley and Jackson (2020) in suggesting that transformation “implies radical ways of doing things to reflect the values aspired to; it is not about quick wins or key performance indicators.” There is then a need to understand the evidence about what factors maximise CPD impact at the individual, team, organisational and system level. Following initial scoping work, the Strategic Research Alliance (SRA) working group, in consultation with Professor Kim Manley and Carolyn Jackson, agreed to complete a rapid review to consider this evidence focusing on the specific question: "What are the factors that enable or optimise CPD impact for learning, development and improvement in the workplace at the individual, team, organisation and system level?

Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium

ABSTRACT Background Advanced-stage mycosis fungoides (MF)/Sezary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. Patients and methods This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). Results Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. Conclusion This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach

Clinical and laboratory experience of vorinostat (suberoylanilide hydroxamic acid) in the treatment of cutaneous T-cell lymphoma

The most common cutaneous T-cell lymphomas (CTCLs) – mycosis fungoides (MF) and Sézary Syndrome – are characterised by the presence of clonally expanded, skin-homing helper-memory T cells exhibiting abnormal apoptotic control mechanisms. Epigenetic modulation of genes that induce apoptosis and differentiation of malignant T cells may therefore represent an attractive new strategy for targeted therapy for T-cell lymphomas. In vitro studies show that vorinostat (suberoylanilide hydroxamic acid or SAHA), an oral inhibitor of class I and II histone deacetylases, induces selective apoptosis of malignant CTCL cell lines and peripheral blood lymphocytes from CTCL patients at clinically achievable doses. In a Phase IIa clinical trial, vorinostat therapy achieved a meaningful partial response (>50% reduction in disease burden) in eight out of 33 (24%) patients with heavily pretreated, advanced refractory CTCL. The most common major toxicities of oral vorinostat therapy were fatigue and gastrointestinal symptoms (diarrhoea, altered taste, nausea, and dehydration from not eating). Thrombocytopenia was dose limiting in patients receiving oral vorinostat at the higher dose induction levels of 300 mg twice daily for 14 days. These studies suggest that vorinostat represents a promising new agent in the treatment of CTCL patients. Additional studies are underway to define the exact mechanism (s) of by which vorinostat induces selective apoptosis in CTCL cells and to further evaluate the antitumour efficacy of vorinostat in a Phase IIb study in CTCL patients

Malignant inflammation in cutaneous T-cell lymphoma: a hostile takeover

Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term "malignant inflammation" as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL