Semyon Melnikov

Neuronal Calcium Sensor-1 and Phosphatidylinositol 4-Kinase β Regulate IgE Receptor-Triggered Exocytosis in Cultured Mast Cells

We examined the possible occurrence and function of neuronal Ca2+ sensor 1 (NCS-1/frequenin) in the mast cell line rat basophilic leukemia, RBL-2H3. This protein has been implicated in the control of neurosecretion from dense core granules in neuronal cells as well as in the control of constitutive secretory pathways in both yeast and mammalian cells. We show that RBL-2H3 cells, secretory cells of the immune system, endogenously express the 22-kDa NCS-1 protein as well as an immune-related 50-kDa protein. Both proteins associate in vivo with phosphatidylinositol 4-kinase β (PI4Kβ) and colocalize with the enzyme in the Golgi region. We show further that overexpression of NCS-1 in RBL-2H3 cells stimulates the catalytic activity of PI4Kβ, increases IgE receptor (FcεRI)-triggered hydrolysis of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and stimulates FcεRI-triggered, but not Ca2+ ionophore-triggered, exocytosis. Conversely, expression of a kinase-dead mutant of PI4Kβ reduces PI4Kβ activity, decreases FcεRI-stimulated phosphatidylinositol 4,5-bisphosphate hydrolysis, and blocks FcεRI-triggered, but not Ca2+ ionophore-triggered, exocytosis. Our results indicate that PI(4)P, produced by the Golgi-localized PI4Kβ, is the rate-limiting factor in the synthesis of the pool of PI(4,5)P2 that serves as substrate for the generation of lipid-derived second messengers in FcεRI-triggered cells. We conclude that NCS-1 is involved in the control of regulated exocytosis in nonneural cells, where it contributes to stimulus-secretion coupling by interacting with PI4Kβ and positive regulation of its activity.

Down-regulating protein kinase C alpha: Functional cooperation between the proteasome and the endocytic system

Ubiquitination, proteasome, caveolae and endosomes have been implicated in controlling protein kinase C alpha (PKC alpha) down-regulation. However, the molecular mechanism remained obscure. Here we show that endosomes and proteasome cooperate in phorbol ester 12-O-tetradecanoyl phorbol acetate (TPA)-induced down-regulation of PKC alpha. We show that following TPA treatment and translocation to the plasma membrane, PKC alpha undergoes multimonoubiquitination prior to its degradation by the proteasome. However, to reach the proteasome, PKC alpha must travel through the endocytic system from early to late endosomes. This route requires functional endosomes, whereby endosomal alkalinization, or ablation, abrogates completely PKC alpha degradation maintaining the enzyme at the plasma membrane. This route also depends on synaptotagmin (Syt) II and the Rab7 GTPase, whereby Syt II knock-down or expression of the GDP-locked Rab7 inactive mutant prevents PKC alpha degradation. We further show that proteasome plays a dual role, where an active proteasome is required for deubiquitination of PKC alpha, a step crucial to prevent PKC alpha targeting to the endocytic recycling compartment. Finally, we show that the association with rafts-localized cell surface proteins that internalize in a clathrin-independent fashion is necessary to allow the trafficking of PKC alpha from the plasma membrane to the proteasome, its ultimate degradation station.

Spirituality as a Predictive Factor for Signing an Organ Donor Card

PURPOSE To examine differences in spirituality, purpose in life, and attitudes toward organ donation between people who signed and those who did not sign an organ donor card. DESIGN A descriptive cross-sectional survey conducted in Israel with a sample of 312 respondents from the general population, of whom 220 (70.5%) signed an organ donor card. Data were collected during April-June 2013. METHODS Participants completed a paper questionnaire and a Web-based questionnaire consisting of four sections: spiritual health, purpose in life, attitudes toward organ donation, and social-demographic questions. Descriptive statistics, t test, chi-square test, and a logistic regression analysis were performed. FINDINGS Differences in mean scores between respondents who signed an organ donor card and those who did not were indicated in transcendental spirituality (p < .01), purpose in life (p < .05), and attitudes toward organ donation (p < .01). No statistically significant difference was found between the groups in the overall spirituality mean score. The spiritual transcendental dimension, individuals purpose in life, and attitudes toward organ donation explained 34.3% of the variance of signing an organ donor card. CONCLUSIONS Signing an organ donor card was found to be correlated with high purpose in life, positive attitudes toward organ donation, and low level of transcendental spirituality. CLINICAL RELEVANCE Nurses should assess the patients spiritual needs in order to construct appropriate programs for promoting signing an organ donor card. Nurses who signed an organ donor card should be encouraged to share this information with their patients.Purpose To examine differences in spirituality, purpose in life, and attitudes toward organ donation between people who signed and those who did not sign an organ donor card. Design A descriptive cross-sectional survey conducted in Israel with a sample of 312 respondents from the general population, of whom 220 (70.5%) signed an organ donor card. Data were collected during April–June 2013. Methods Participants completed a paper questionnaire and a Web-based questionnaire consisting of four sections: spiritual health, purpose in life, attitudes toward organ donation, and social-demographic questions. Descriptive statistics, t test, chi-square test, and a logistic regression analysis were performed. Findings Differences in mean scores between respondents who signed an organ donor card and those who did not were indicated in transcendental spirituality (p < .01), purpose in life (p < .05), and attitudes toward organ donation (p < .01). No statistically significant difference was found between the groups in the overall spirituality mean score. The spiritual transcendental dimension, individuals purpose in life, and attitudes toward organ donation explained 34.3% of the variance of signing an organ donor card. Conclusions Signing an organ donor card was found to be correlated with high purpose in life, positive attitudes toward organ donation, and low level of transcendental spirituality. Clinical Relevance Nurses should assess the patients spiritual needs in order to construct appropriate programs for promoting signing an organ donor card. Nurses who signed an organ donor card should be encouraged to share this information with their patients.

Closing an Open Psychiatric Ward: Organizational Change and Its Effect on Staff Uncertainty, Self-Efficacy, and Professional Functioning

PURPOSE Converting an open psychiatric ward to a closed one can be threatening and stressful for the medical and nursing staff involved. This study describes the effects of this change, in particular the before-after correlation among self-efficacy, professional functioning, and uncertainty. DESIGN AND METHODS Forty-four staff participated, completing pre-/poststructured questionnaires. FINDINGS Uncertainty was higher before the conversion than after the conversion. Professional functioning declined after the conversion. Self-efficacy was positively correlated with pre- and postconversion functioning, but negatively correlated with postconversion uncertainty. PRACTICE IMPLICATIONS It is important to prepare staff for this significant organizational change. Suggestions for prechange interventions are offered.

Feelings of indebtedness and guilt toward donor and immunosuppressive medication adherence among heart transplant (HTx) patients, as assessed in a cross‐sectional study with the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS)

Nonadherence (NA) to immunosuppressive (IS) medications after organ transplant is a major risk factor for transplant failure, morbidity, and treatment costs. This study examined the association between feelings of indebtedness and guilt toward the donor, and IS medication adherence among HTx patients.

Between a Rock and a Hard Place: Ethical and Professional Dilemmas in a Psychiatric Hospital Under Missile Attacks

BACKGROUND: Israeli hospitals must continuously develop various mechanisms to protect both patients and staff against the physical threat of missile attacks during war situations. OBJECTIVES: To examine the difficulties and dilemmas with which the staff of a psychiatric hospital had to deal during missile attacks. DESIGN: A quality improvement project consisting of three stages (1) establishment of a steering committee; (2) execution of a staff nurses’ focus group; and (3) categorization of issues raised and suggestions for care improvement in future emergencies. RESULTS: The project stressed the challenges of dealing with restrained patients during missile alarms, waking up patients or dealing with those who refuse to enter the protected area, mismatching of the security needs in protected areas, and institutionalized emotional support for staff members. CONCLUSION: Suitable policies for clinical and management behavior and for information transfer between management and wards are essential during a continuous emergency.

Differences between new immigrants from the former Soviet union and veteran residents in knowledge, perception, and risk factors of stroke

Background:Stroke is the fourth most common cause of death in developed countries and a leading cause of acquired disability in adults. Awareness of risk factors and warning signs for stroke has a considerable impact on early arrival at the hospital and early thrombolytic treatment. Delays in seeking medical treatment following the onset of stroke symptoms have been shown to be more common among ethnic minorities. Objective:The aim of the current study was to examine stroke awareness and knowledge among new immigrants from the Former Soviet Union (IFSUs) compared with veteran residents (VRs). Methods:The study was conducted by students of the nursing master of arts program. Data were collected during March 2010 and June 2014. Trained registered nurses conducted interviews, using a structured, pretested, open-ended questionnaire. Participants were recruited by a snowball method from among the interviewers’ friends and family members, 40 years or older with no history of stroke. Results:A total of 643 Israelis, 420 VRs (65.3%) and 223 IFSUs (34.7%), were interviewed; 40.7% were men, with a mean age of 52.6 (SD, 9.3) years. Compared with VRs, IFSUs were more likely to report previous myocardial infarction (P = .022), hypertension (P < .001), and diabetes (P = .012). The mean number of stroke warning signs reported by IFSUs was higher than that reported by VRs (P = .031). When asked about risk factors for stroke, IFSUs more often stated hypertension (P = .03), whereas VRs more often reported family history (P = .03). Immigrants from the Former Soviet Union were more aware of strategies for the prevention of stroke than VRs (P = .02). The preferred sources of information about stroke for IFSUs, as distinguished from VRs, were personal doctors (P = .001) and radio programs (P = .03). Conclusions:Veteran residents showed lower levels of knowledge about stroke. Educational campaigns aimed at increasing knowledge of stroke among Israel’s general population in Israel, as well as culturally targeting specific subgroups, are recommended.

Transcendental Spirituality and Acquaintance With the Activities of the Domestic National Transplant Center as Factors Shaping Attitudes Toward Organ Donation.

Context: Organ donation has been shown to be perceived as inappropriate by religiously observant individuals. The impact of spirituality level on attitudes toward organ donation has not been broadly explored. Objective: To explore the contribution of ethnicity, spirituality, level of religious observance, and acquaintance with the activities of the Israel National Transplant Center (INTC) to forming attitudes toward organ donation among Jews and Muslim Arabs in Israel. Design: A descriptive cross-sectional survey. Participants: Three hundred five (65.2%) Jewish and 163 (34.8%) Muslim Arab respondents living in Israel. Results: Jewish respondents had more positive attitudes toward organ donation than Muslim Arabs. Muslim Arabs had a higher mean spirituality score than Jews. Gender, age, ethnicity, level of religious observance, education, 4 spirituality dimensions, and acquaintance with the activities of the INTC explained 41.5% of the variance in attitudes to organ donation. Transcendental spirituality, acquaintance with the activities of the INTC, and level of religious observance had the highest contribution to explaining attitudes to organ donation, while gender and age had a low contribution. Ethnicity, education, and the 3 other spirituality dimensions were not found to have a significant contribution. Conclusion: A multifaceted approach to improving attitudes toward organ donation among Jews and Muslim Arabs in Israel is important.

Experiences, behaviors, and perceptions of registered nurses regarding research ethics and misconduct

Background: Nurses engaging in research are held to research ethics standards. Research aim: Examine experiences, behaviors, and perceptions of nurses in Israel regarding research ethics and explore possible related factors. Research design: An original investigator-designed self-administered questionnaire measured five variables: (a) ethics in research, (b) encountered research misconduct during the course of one’s studies, (c) the inclination to fabricate data, (d) the inclination to select or omit data, and (e) knowledge of research misconduct in the workplace. Additionally, demographic data were collected. Participants and research context: The questionnaire was completed by 151 Israeli registered nurses. 10.2% hold a PhD, 34 % hold an MA, 42.2% hold a BA, and 13.6% with no academic degree. Ethical considerations: The study was approved by the University’s ethics committee; anonymity and consent of the respondents were respected. Findings: Registered nurses’ level of studies achieved was significantly associated with a lower inclination to fabricate data, with one exception—PhD nurses were more inclined to fabricate data than nurses with a Master’s degree. A trend was found in which a higher level of studies is associated with higher knowledge of research misconduct in the workplace. Discussion: Results indicate that nurses’ perceptions of research ethics change throughout their academic studies, indicating a positive influence of level of studies, research experience, and work experience on ethics perceptions. Nevertheless, PhD nurses showed a greater inclination to actually select, omit, or even fabricate data than MA nurses. This may be related to pressure to publish. Conclusion: PhD nursing programs should include ethics training. Academic faculty members should serve as role models regarding research integrity. Research ethics deserves further emphasis on all levels of nurse education in Israel, as well as in the nurses’ code of ethics and related documents. This may positively impact ethical research practices.