Motivations and challenges of Israeli nurses on their journey to a PhD: A qualitative study.

AIM: This qualitative study aimed to examine the motivations and challenges encountered by Israeli nurses during their journey to achieve a doctoral degree (PhD). BACKGROUND: The increasing numbers of nurses studying for a doctoral degree may contribute to improving nursing education, expanding the body of knowledge and promoting the status of nursing as a research profession. However, many countries have reported a shortage in nurses with doctoral degrees. DESIGN: Qualitative content analysis study using semi-structured interviews. METHODS: Sixteen senior nurses (mean age 47.35 years, 75% women) who completed their doctoral studies in the past five years were interviewed. The interviews were transcribed and their content was analyzed inductively. COREQ checklist was used to report the study. RESULTS: The ability to persevere in doctoral studies was related to the support provided by the learning environment as well as to family support. External barriers were related to administrative bureaucracy, tedious search for a mentor, unsupportive workplace and socio-economic burdens. PhD studies were perceived as a means for self-fulfillment, while major motivators were aspiration for professional advancement, a responsibility for promoting the image of nursing and a lack of recognition by colleagues. CONCLUSIONS: Nurses study for doctoral degrees in order to advance their career and achieve personal fulfillment, as well as to increase the prestige of the nursing as profession. To allow nurses with PhD to fulfill their abilities and to advance the nursing profession, their research and academic support should be increased, and appropriate professional positions should be developed. TWEETABLE ABSTRACT: This study highlights the facilitators of doctoral studies such as family and academic support, a strong need for personal and professional fulfillment, and a desire for professional change, and obstacles such as academic and bureaucratic barriers, low wage increases, and a lack of recognition of nursing by the medical world.

Diabetes nurse practitioners in the shadow of the COVID-19 pandemic: Challenges, insights, and suggestions for improvement.

PURPOSE: The study examined the role of diabetes nurse practitioners (DiNPs) and their contribution to the quality of care of individuals with diabetes during the COVID-19 pandemic. Specifically, we examined the benefits and barriers of using telemedicine for managing diabetes. DESIGN: A descriptive qualitative research using content analysis of interviews. METHODS: Participants were invited through the National DiNPs' Forum. Semi-structured interviews were conducted with 24 licensed DiNPs (age range, 37-58 years) who were involved in the clinical care of individuals with diabetes during the COVID-19 pandemic. The interviews were recorded and transcribed, and content analysis was then used for extracting themes and their related categories. FINDINGS: Content analysis revealed five themes: (a) Benefits and barriers of remote diabetes treatment; (b) Teamwork and its implications to DiNPs; (c) Technological challenges, resourcefulness, and creativity; (d) Changed perception of DiNP roles; and (e) Cultural diversity and improving communication skills. The benefits of telemedicine included improved control, efficiency, convenience and satisfaction, while the disadvantages of this method included the inability to provide optimal practical guidance on technical aspects of physical assessments and care. Sectors with limited digital literacy and language barriers had difficulties using telemedicine. Teamwork was reported as a facilitator to managing treatment. Telemedicine provided an opportunity for DiNPs to become more efficient and focused and to clearly define their role in the organization. CONCLUSIONS: The COVID-19 pandemic has posed new challenges. Along with the need to adapt the therapeutic approach to remote care, DiNPs improved their professional status, acquired new skills, and were satisfied with their personal and professional growth. CLINICAL RELEVANCE: Telemedicine should become an integral part of diabetes management to enable access to populations who cannot come to the clinic. Patients should be guided on using telemedicine platforms.

Biobanking in the COVID-19 Era and Beyond: Part 1. How Early Experiences Can Translate into Actionable Wisdom.

The era of COVID-19 has brought about a number of novel challenges for the global biobanking community. To better position the biobanking community to cope with current and future challenges, the International Society for Biological and Environmental Repositories (ISBER) COVID-19 Response Task Force was convened to identify needs and gaps in biobanking tools (existing resources that support good practice), for example, standards, best practices, business, etc. and to make recommendations to benefit the community. Toward these goals, the Task Force assembled a set of questions to explore individual biobanks' experiences, with emphasis on identification of key challenges and approaches, including tools employed. A survey was designed with the use of these questions and administered by ISBER. This article presents a summary of the aggregated data obtained from the survey responses, illustrating some of the major issues encountered and identifying which tools the survey respondents found most useful. In particular, this article focuses on the challenges identified during the early months of the COVID-19 era. Recommendations are provided to support biobank emergency preparedness for the future, address lessons learned, and propose solutions to bridge identified gaps. The analysis and the complete survey dataset will also inform the larger Task Force goal to develop specific tool recommendations.

Related to testes-specific, vespid and pathogenesis protein-1 is regulated by methylation in glioblastoma.

Related to testes-specific, vespid and pathogenesis protein-1 (RTVP-1), also known as glioma pathogenesis-related protein 1, is highly expressed and has oncogenic features in glioblastoma (GBM; World Health Organization class IV). Promoter methylation has been found to control RTVP-1 expression in prostate carcinoma, Wilms' tumor, acute myeloid leukemia and melanoma. In this bi-institutional study, the methylation status of RTVP-1 in astrocytic brain malignancies (GBM and oligodendroglioma) was examined. The RTVP-1 promoter was hypomethylated in GBM compared with non-tumor brain samples, but was hypermethylated in oligodendroglioma. RTVP-1 methylation correlated with RTVP-1 expression at the mRNA level. In GBM, hypermethylation of the RTVP-1 promoter was associated with improved overall survival although with no statistical significance.

A comparative analysis of total serum miRNA profiles identifies novel signature that is highly indicative of metastatic melanoma: a pilot study.

CONTEXT: Quantification of circulating microRNAs (miRNAs) has recently become feasible and reliable, with most efforts focusing on miRNAs overexpressed by cancer cells. OBJECTIVE: Identification of a characteristic circulating miRNAs profile in melanoma patients. METHODS: We conducted a pilot study comprised of unbiased qPCR comparison of serum miRNA profiles between metastatic melanoma patients and healthy donors. RESULTS: Loss of two normal serum-miRNAs, miR-29c and miR-324-3p, is highly indicative of metastatic melanoma. Hierarchical clustering analysis supported the results and clearly distinguished melanoma patients from healthy donors, metastatic colon and renal cancer patients. DISCUSSION AND CONCLUSIONS: This approach is independent of tumor heterogeneity and is expected to have superior biomarker performances.

[Tissue repositories for research at Sheba Medical Center(SMC].

INTRODUCTION: Cancer is the number one cause of death in both genders. Breakthroughs in the understanding of cancer biology, the identification of prognostic factors, and the development of new treatments are increasingly dependent on access to human cancer tissues with linked clinicopathological data. Access to human tumor samples and a large investment in translational research are needed to advance this research. The SMC tissue repositories provide researchers with biological materials, which are essential tools for cancer research. GOALS: SMC tissue repositories for research aim to collect, document and preserve human biospecimens from patients with cancerous diseases. This is in order to provide the highest quality and well annotated biological biospecimens, used as essential tools to achieve the growing demands of scientific research needs. Such repositories are partners in acceLerating biomedical research and medical product development through clinical resources, in order to apply best options to the patients. METHODS: Following Institutional Review Board approval and signing an Informed Consent Form, the tumor and tumor-free specimens are coLLected by a designated pathologist at the operating room only when there is a sufficient amount of the tumor, in excess of the routine needs. Blood samples are collected prior to the procedure. Other types of specimens collected include ascites fluid, pleural effusion, tissues for Optimal Cutting Temperature [OCT] and primary culture etc. Demographic, clinical, pathologicaL, and follow-up data are collected in a designated database. SMC has already established several organ or disease-specific tissue repositories within different departments. SUMMARY: The foundation of tissue repositories requires the concentrated effort of a multidisciplinary team composed of paramedical, medical and scientific professionals. Research projects using these specimens facilitate the development of 'targeted therapy', accelerate basic research aimed at clarifying molecular mechanisms involved in cancer, and support the development of novel diagnostic tools.

Establishing and sustaining a biorepository network in Israel: challenges and progress.

Over the past 5 years, using European and North American biobanks as models, the grass-roots establishment of independently operating biobanks has occurred virtually simultaneously in large Israeli teaching hospitals. The process of establishing a national biorepository network in Israel has progressed slowly, sustained mainly by a few proponents working together on a personal level. Slow progress has been due to limited funding and the lack of a legal framework specific to biobanking activities. Recently, due to increasing pressure from the scientific community, the government has earmarked funds for a national biorepository network, and the structure is now being established. In forming a network, Israel's biobanks face certain difficulties, particularly lack of support. Additional challenges include harmonization of standard operating procedures, database centralization, and use of a common informed consent form. In this article, we highlight some of the issues faced by Israel's biobank managers in establishing and sustaining a functional biobank network, information that could provide guidance for other small countries with limited resources.

TMPRSS2/ERG promotes epithelial to mesenchymal transition through the ZEB1/ZEB2 axis in a prostate cancer model.

Prostate cancer is the most common non-dermatologic malignancy in men in the Western world. Recently, a frequent chromosomal aberration fusing androgen regulated TMPRSS2 promoter and the ERG gene (TMPRSS2/ERG) was discovered in prostate cancer. Several studies demonstrated cooperation between TMPRSS2/ERG and other defective pathways in cancer progression. However, the unveiling of more specific pathways in which TMPRSS2/ERG takes part, requires further investigation. Using immortalized prostate epithelial cells we were able to show that TMPRSS2/ERG over-expressing cells undergo an Epithelial to Mesenchymal Transition (EMT), manifested by acquisition of mesenchymal morphology and markers as well as migration and invasion capabilities. These findings were corroborated in vivo, where the control cells gave rise to discrete nodules while the TMPRSS2/ERG-expressing cells formed malignant tumors, which expressed EMT markers. To further investigate the general transcription scheme induced by TMPRSS2/ERG, cells were subjected to a microarray analysis that revealed a distinct EMT expression program, including up-regulation of the EMT facilitators, ZEB1 and ZEB2, and down-regulation of the epithelial marker CDH1(E-Cadherin). A chromatin immunoprecipitation assay revealed direct binding of TMPRSS2/ERG to the promoter of ZEB1 but not ZEB2. However, TMPRSS2/ERG was able to bind the promoters of the ZEB2 modulators, IL1R2 and SPINT1. This set of experiments further illuminates the mechanism by which the TMPRSS2/ERG fusion affects prostate cancer progression and might assist in targeting TMPRSS2/ERG and its downstream targets in future drug design efforts.

Transcriptional programs following genetic alterations in p53, INK4A, and H-Ras genes along defined stages of malignant transformation.

The difficulty to dissect a complex phenotype of established malignant cells to several critical transcriptional programs greatly impedes our understanding of the malignant transformation. The genetic elements required to transform some primary human cells to a tumorigenic state were described in several recent studies. We took the advantage of the global genomic profiling approach and tried to go one step further in the dissection of the transformation network. We sought to identify the genetic signatures and key target genes, which underlie the genetic alterations in p53, Ras, INK4A locus, and telomerase, introduced in a stepwise manner into primary human fibroblasts. Here, we show that these are the minimally required genetic alterations for sarcomagenesis in vivo. A genome-wide expression profiling identified distinct genetic signatures corresponding to the genetic alterations listed above. Most importantly, unique transformation hallmarks, such as differentiation block, aberrant mitotic progression, increased angiogenesis, and invasiveness, were identified and coupled with genetic signatures assigned for the genetic alterations in the p53, INK4A locus, and H-Ras, respectively. Furthermore, a transcriptional program that defines the cellular response to p53 inactivation was an excellent predictor of metastasis development and bad prognosis in breast cancer patients. Deciphering these transformation fingerprints, which are affected by the most common oncogenic mutations, provides considerable insight into regulatory circuits controlling malignant transformation and will hopefully open new avenues for rational therapeutic decisions.

Transactivation of the EGR1 gene contributes to mutant p53 gain of function.

Tumor-associated mutants of the p53 tumor suppressor protein exert biological activities compatible with an oncogenic gain of function. To explore the underlying molecular mechanism, we performed microarray analysis, comparing p53-null cells to mutant p53-expressing cells. One of the genes up-regulated in the presence of mutant p53 was EGR1, a transcription factor implicated in growth control, apoptosis, and cancer. EGR1 induction by various types of stress is markedly augmented in cells expressing mutant p53. Moreover, chromatin immunoprecipitation analysis indicates that mutant p53 is physically associated with the EGR1 promoter. Functional assays indicate that induction of EGR1 by mutant p53 contributes to enhanced transformed properties and resistance to apoptosis. We propose that EGR1 is a significant contributor to mutant p53 gain of function.

The role of p53 in base excision repair following genotoxic stress.

The p53 tumor suppressor protein is involved in apoptosis and cell cycle checkpoints. We have shown recently that p53 also facilitates base excision repair (BER). To further examine p53 involvement in the regulation of BER we chose to focus on 3-methyladenine DNA glycosylase (3-MeAde DNA glycosylase), the first enzyme acting in the BER pathway. 3-MeAde DNA glycosylase activity was found to be modulated by the p53 protein. This modulation was dependent on the type of genotoxic stress used. Gamma-irradiation damage resulted in activation of glycosylase, which was enhanced by p53. Doxorubicin and hydrogen peroxide (H2O2) treatment, although inducing p53 stabilization, did not cause the activation of glycosylase. Nitric oxide (NO) resulted in activation of 3-MeAde DNA glycosylase. Surprisingly this activation was down regulated by wild-type p53. The down regulation of 3-MeAde DNA glycosylase activity was due to trans repression of glycosylase mRNA by p53. Furthermore, we found that AP endonuclease (APE) activity was not altered by NO. Our study provides evidence for a possible antimutagenic role for p53 following exposure of cells to NO species. In the absence of p53, NO exposure results in elevation of 3-MeAde DNA glycosylase activity that results in elevation in the number of AP sites in DNA. At the same time, APE activity does not rise and removal of the AP sites is not further processed resulting in a mutator phenotype. When p53 is present, it down regulates the transcription of 3-MeAde DNA glycosylase. This provides a new model by which p53 prevents the creation of a mutator phenotype.

Biomonitoring air pollution with the desert lichen Ramalina maciformis.

To investigate the environmental impact of anthropogenic activity in the Negev Desert, we monitored the following in order to determine the physiological integrity of the epilithic fruticose lichen Ramalina maciformis: (1) production of ethylene; (2) potential quantum yield of photosystem II expressed as chlorophyll fluorescence ratio Fv/Fm; and (3) electrolyte leakage of cell membranes in terms of electric conductivity. The degree of pollution was assessed by measuring the amounts of B, Cd, Co, Cu, Fe, K, Mg, Mn, Na, Ni, P, Pb, Sr and Zn in the lichen thallus. Some of the lichen-carrying stones collected in the relatively unpolluted control site were relocated on the same hill, to test the possible impact of relocation. An additional amount of lichen-carrying stones was marked as controls. The greater part of the lichen-carrying stones was transferred to 10 biomonitoring sites in and around Ramat Hovav, an industrial area in the Negev Desert, Israel. Transplanted lichen in polluted sites contained higher amounts of mineral elements than lichens in the control site after an exposure period of 7 months. Statistical analysis revealed positive correlation of ethylene production and Ni content, negative correlation of Fv/Fm ratios and B, Cu, Mn, Na, Ni, Sr and Zn, and positive correlation of electric conductivity and B, Mn, Ni and Sr. Both elemental content and physiological alterations in transferred samples of R. maciformis point to a high degree of contamination in Ramat Hovav. The present study suggests that the lichen R. maciformis should be classified as a sensitive species endangered by anthropogenic activity in the desert. Furthermore, this lichen species is likely to be suitable as a bioindicator of pollution in other parts of the Negev Desert. Ethylene production and electric conductivity as parameters of lichen-vitality, indicated stress in 5 of the 12 biomonitoring sites (42%) and may therefore be considered as more sensitive than the Fv/Fm ratio, which indicated stress in 3 of the 12 sites (25%).

SCAR is a primary regulator of Arp2/3-dependent morphological events in Drosophila.

The Arp2/3 complex and its activators, Scar/WAVE and Wiskott-Aldrich Syndrome protein (WASp), promote actin polymerization in vitro and have been proposed to influence cell shape and motility in vivo. We demonstrate that the Drosophila Scar homologue, SCAR, localizes to actin-rich structures and is required for normal cell morphology in multiple cell types throughout development. In particular, SCAR function is essential for cytoplasmic organization in the blastoderm, axon development in the central nervous system, egg chamber structure during oogenesis, and adult eye morphology. Highly similar developmental requirements are found for subunits of the Arp2/3 complex. In the blastoderm, SCAR and Arp2/3 mutations result in a reduction in the amount of cortical filamentous actin and the disruption of dynamically regulated actin structures. Remarkably, the single Drosophila WASp homologue, Wasp, is largely dispensable for these numerous Arp2/3-dependent functions, whereas SCAR does not contribute to cell fate decisions in which Wasp and Arp2/3 play an essential role. These results identify SCAR as a major component of Arp2/3-dependent cell morphology during Drosophila development and demonstrate that the Arp2/3 complex can govern distinct cell biological events in response to SCAR and Wasp regulation.