Expression and function of calcium-activated potassium channels following in-stent restenosis in a porcine coronary artery model

AbstractIn-stent restenosis (ISR) occurs due to proliferation and migration of smooth muscle cells from media to intima resulting in re-narrowing of the vessel lumen. This study aims to investigate changes in the three main KCa channels in response to stent implantation in porcine coronary arteries as their expression and function in ISR is yet to be defined. Twenty-eight days after stent implantation, immunofluorescent labelling with anti-desmin and anti-vWF confirm the presence of both endothelial and smooth muscle cells within the neointimal layer. Using real-time PCR, significant increase in the SK3 and IKCa and BKCa channel mRNA was observed within this layer alone. Western blot analysis confirms the expression of KCa channels in neointima. Although expression of BKCa was increased in the neointima in comparison with medial region of the artery, microelectrode recordings showed that the function of this channel was unchanged. However, the presence of functional BKCa in both medial and intimal cells suggests that smooth muscle cells migration may contribute to neointimal hyperplasia.Functional analysis using 1-EBIO and Bradykinin produced hyperpolarization of neointimal but not medial myocytes, which indicated the expression of functional endothelial SK3 and IKCa in the former and not in the latter. The expression of IKCa and SK3 within the neointimal layer suggested that some degree of recovery of both endothelial as well as smooth muscle regeneration had occurred. Future development of selective modulators of IKCa and SK3 channels may decrease the progression of ISR and improve coronary vascular function after stent placement, and is an area for future investigation

Tanggung Jawab Sosial Perusahaan: Aktualisasi Ajaran Jaudatul Ada (Penyelesaian yang Baik) dalam Bisnis (Studi Kasus Bsm)

As a form of accountability for its economic activities, every company in the world must performCSR activities, including companies in Indonesia. Unfortunately, the values contained in current CSR reporting contain only secular activities, whereas Indonesia is a country with 200million Muslims who are entitled to use Islamic religious values in their lives that are includedin economic activities, including CSR. This study aims to find the appropriate Islamic valuesand can be applied in CSR activities. This study finds value in Islam that can be a referencecompany, in terms of this research is syariah bank, for CSR activities, namely the value ofJaudatul Ada (good settlement)

Qualitative study on mental health and well-being of Syrian refugees and their coping mechanisms towards integration in the UK

Objective This study aimed to explore the mental well-being of Syrian refugees and identify their coping mechanisms and pathways towards integration into new communities. Design Qualitative study using in-depth semi-structured interviews. Setting and participants Adult Syrian refugees (>18 years old) currently residing in South East of England. Results 12 participants (3 women and 9 men) took part in the study, all were born in Syria and the majority (n=9) were over 45 years of age. Our findings show that Syrian refugees face constant challenges as they try to integrate into a new society. Loss of and separation from loved ones as well as the nostalgia for the homeland were often cited as a source of psychological distress that created an overwhelming sense of sadness. Participants reported that they struggled for connectedness due to cultural difference and the problematic nature of rapidly formed migrant communities in their new setting. They believed in ‘being their own doctor’ and turning to faith, ritual and nature for healing and comfort. Taboo and stigma around mental health and language barriers were cited as barriers to accessing mental healthcare services. Conclusion Past experiences and present challenges frame Syrian refugees’ sense of well-being, impact use of healthcare and risk future mental health problems. It is hoped that this study will act as a catalyst for further research on this vulnerable group to promote integration, community support and culturally sensitive mental health services

Applications of coxsackievirus A21 in oncology

The clinical management of cancer continues to be dominated by macroscopic surgical resection, radiotherapy, and cytotoxic drugs. The major challenge facing oncology is to achieve more selective, less toxic and effective methods of targeting disseminated tumors, a challenge oncolytic virotherapy may be well-placed to meet. Characterization of coxsackievirus A21 (CVA21) receptor-based mechanism of virus internalization and lysis in the last decade has suggested promise for CVA21 as a virotherapy against malignancies which overexpress those receptors. Preclinical studies have demonstrated proof of principle, and with the results of early clinical trials awaited, CVA21 may be one of the few viruses to demonstrate benefit for patients. This review outlines the potential of CVA21 as an oncolytic agent, describing the therapeutic development of CVA21 in preclinical studies and early stage clinical trials. Preclinical evidence supports the potential use of CVA21 across a range of malignancies. Malignant melanoma is the most intensively studied cancer, and may represent a “test case” for future development of the virus. Although there are theoretical barriers to the clinical utility of oncolytic viruses like CVA21, whether these will block the efficacy of the virus in clinical practice remains to be established, and is a question which can only be answered by appropriate trials. As these data become available, the rapid journey of CVA21 from animal studies to clinical trials may offer a model for the translation of other oncolytic virotherapies from laboratory to clinic

On the effect of heterovalent substitutions in ruthenocuprates

We discuss the properties of superconducting derivatives of the RuSr2GdCu2O8 (1212-type) ruthenocuprate, for which heterovalent doping has been achieved through partial substitution of Cu ions into the RuO2 planes (Ru1-xSr2GdCu2+xO8-d, 0<x<0.75, Tcmax=72 K for x=0.3-0.4) and Ce ions into the Gd sites (RuSr2Gd1-yCeyCu2O8, 0<y<0.1). The measurements of XANES, thermopower, and magnetization under external pressure reveal an underdoped character of all compounds. Muon spin rotation experiments indicate the presence of magnetic order at low temperatures (Tm=14-2 K for x=0.1-0.4). Properties of these two series lead us to the qualitative phase diagram for differently doped 1212-type ruthenocuprates. The difference in temperature of magnetic ordering found for superconducting and non-superconducting RuSr2GdCu2O8 is discussed in the context of the properties of substituted compounds. The high pressure oxygen conditions required for synthesis of Ru1-xSr2RECu2+xO8-d, have been extended to synthesis of a Ru1-xSr2Eu2-yCeyCu2+xO10-d series. The Cu->Ru doping achieved in these phases is found to decrease the temperature for magnetic ordering as well the volume fraction of the magnetic phase.Comment: Proceedings of the 3rd Polish-US Workshop on Magnetism and Superconductivity of Advanced Materials, July 14-19, 2002, Ladek Zdroj (Poland) to appear in Physica

Magnetic phase diagram of cubic perovskites SrMn_1-xFe_xO_3

We combine the results of magnetic and transport measurements with Mossbauer spectroscopy and room-temperature diffraction data to construct the magnetic phase diagram of the new family of cubic perovskite manganites SrMn_1-xFe_xO_3. We have found antiferromagnetic ordering for lightly and heavily Fe-substituted material, while intermediate substitution leads to spin-glass behavior. Near the SrMn_0.5Fe_0.5O_3 composition these two types of ordering are found to coexist and affect one another. The spin glass behavior may be caused by competing ferro- and antiferromagnetic interactions among Mn^4+ and observed Fe^3+ and Fe^5+ ions.Comment: 8 pages, 10 figures, revtex, accepted to Phys. Rev.

Fitter women did not have attenuated hemodynamic responses to psychological stress compared with age-matched women with lower levels of fitness

According to the \u27cross stressor adaptation hypothesis\u27, regular exercise acts as a buffer against the detrimental effects of stress. Nevertheless, evidence that higher levels of cardiorespiratory fitness moderate hemodynamic responses to acute psychological stress is inconclusive, especially in women. Women aged 30-50 years (in the mid-follicular phase of the menstrual cycle) with higher (n = 17) and lower (n = 17) levels of fitness were subjected to a Trier Social Stress Test (TSST). Continuous, non-invasive measurements were made of beat-to-beat, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), stroke volume (SV), cardiac output (CO), left ventricular ejection time (LVET), maximum slope, pulse interval (PI) and total peripheral resistance (TPR). Maximal oxygen consumption was significantly (p&lt;0.001) higher in the \u27higher fit\u27 women. Lower fit women had higher fasting glucose, resting heart rate, waist to hip ratios and elevated serum triglyceride and cholesterol/ HDL ratios compared with higher fit women (p&lt;0.05 for all). While all measured parameters (for both groups)displayed significant (p&lt;0.001) responses to the TSST, only HR, PI and LVET differed significantly between higher and lower fit women (p&lt;0.001 for all) with the higher fit women having the larger response in each case. It was also found that higher fit women had significantly shorter time to recovery for maximum slope compared with the lower fit women. These findings provide little support for the notion that higher levels of cardiorespiratory fitness result in lower cardiovascular responsivity to psychological stress in women but may indicate that lower fit women have blunted responses to stress

The CARE accelerator R&D programme in Europe

Published online on JACoWCARE, an ambitious and coordinated programme of accelerator research and developments oriented towards high energy physics projects, has been launched in January 2004 by the main European laboratories and the European Commission. This project aims at improving existing infrastructures dedicated to future projects such as linear colliders, upgrades of hadron colliders and high intensity proton drivers. We describe the CARE R&D plans, mostly devoted to advancing the performance of the superconducting technology, both in the fields of RF cavities for electron or proton acceleration and of high field magnets, as well as to developing high intensity electron and proton injectors. We highlight some results and progress obtained so far