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Expansion of beta cells from the limited number of adult human islet donors is an attractive prospect for increasing cell availability for cell therapy of diabetes. However, attempts at expanding human islet cells in tissue culture result in loss of beta-cell phenotype. Using a lineage-tracing approach we provided evidence for massive proliferation of beta-cell-derived (BCD) cells within these cultures. Expansion involves dedifferentiation resembling epithelial-mesenchymal transition (EMT). Epigenetic analyses indicate that key beta-cell genes maintain open chromatin structure in expanded BCD cells, although they are not transcribed. Here we investigated whether BCD cells can be redifferentiated into beta-like cells.Redifferentiation conditions were screened by following activation of an insulin-DsRed2 reporter gene. Redifferentiated cells were characterized for gene expression, insulin content and secretion assays, and presence of secretory vesicles by electron microscopy. BCD cells were induced to redifferentiate by a combination of soluble factors. The redifferentiated cells expressed beta-cell genes, stored insulin in typical secretory vesicles, and released it in response to glucose. The redifferentiation process involved mesenchymal-epithelial transition, as judged by changes in gene expression. Moreover, inhibition of the EMT effector SLUG (SNAI2) using shRNA resulted in stimulation of redifferentiation. Lineage-traced cells also gave rise at a low rate to cells expressing other islet hormones, suggesting transition of BCD cells through an islet progenitor-like stage during redifferentiation.These findings demonstrate for the first time that expanded dedifferentiated beta cells can be induced to redifferentiate in culture. The findings suggest that ex-vivo expansion of adult human islet cells is a promising approach for generation of insulin-producing cells for transplantation, as well as basic research, toxicology studies, and drug screening.

Measurements of bone morphometry and remodeling have been shown to reflect bone strength and can be used to diagnose degenerative bone disease. In this study, in vivo and ex vivo magnetic resonance imaging (MRI) techniques to assess trabecular and cortical bone properties have been compared to each other and to histology as a novel means for the quantification of bone. Femurs of C57Bl/6 mice were examined both in vivo and ex vivo on an 11.7 T MRI scanner, followed by histologic processing and morphometry. A thresholding analysis technique was applied to the MRI images to generate contour lines and to delineate the boundaries between bone and marrow. Using MRI, an optimal correlation with histology was obtained with an in vivo longitudinal sectioned short echo time gradient-echo versus an in vivo long echo time spin-echo sequence or an ex vivo pulse sequence. Gradient-echo images were acquired with a maximum in-plane resolution of 35 μm. Our results demonstrated that in both the in vivo and ex vivo data sets, the percent area of marrow increases and percent area of trabecular bone and cortical bone thickness decreases moving from the epiphyseal growth plate to the diaphysis. These changes, observed with MRI, correlate with the histological data. Investigations using in vivo MRI gradient-echo sequences consistently gave the best correlation with histology. Our quantitative evaluation using both ex vivo and in vivo MRI was found to be an effective means to visualize non-invasively the normal variation in trabecular and cortical bone as compared to a histological “gold standard” The experiments validated in vivo MRI as a potential high resolution technique for investigating both soft tissue, such as marrow, and bone without radiation exposure. [Copyright &y& Elsevier]

: BackgroundOur previous studies have shown that the injection of B16F1 melanoma cells into the mesenteric vein can induce the rapid local release of nitric oxide (NO) in the liver, causing apoptosis of the melanoma cells in the liver sinusoids and inhibiting the subsequent formation of hepatic metastases. In this study, we have investigated the distribution and cellular source of NO in this model.: Materials and methodsIn situ liver perfusion was established in both wild-type (wt) and endothelial nitric oxide synthase knockout (eNOS KO) C57BL/6 mice. A specific fluorescent NO probe, 4,5-diaminofluorescein diacetate (DAF-2 DA) (5 μmol/L), was perfused into the portal venous system to label the liver tissue. Then, a MitoTracker Orange labeled B16F1 melanoma cell suspension (2 × 106 cells/ml) was injected through a portal vein catheter by a peristaltic pump. Images of the liver tissue were taken by confocal microscopy from a selected area to determine the cellular source of NO. For quantification, the fluorescence intensity of this area was measured over time by Fluoview software.: ResultsDiaminotriazolofluorescein (DAF-2T) fluorescence (indicating NO generation) was detected in hepatic parenchymal cells located in the periportal region in both wt C57BL/6 and eNOS KO C57BL/6 mice and was intensified by increased flow rate in the portal venous system. The B16F1 cells arrested in the periportal sinusoids, corresponding to zone 1 of the hepatic acinus. DAF-2T fluorescence was expressed by both sinusoidal lining cells and hepatocytes at the site of tumor cell arrest. The fluorescence intensity of these cells increased ∼2-fold over a time of 500 s. In contrast, there was no increase in the fluorescence intensity of the sinusoidal lining cells and hepatocytes in mice perfused with buffer or in eNOS KO mice perfused with B16F1 cells.: ConclusionThis study demonstrates that NO is produced by hepatic parenchymal cells mainly located in the periportal zones and that the arrest of the B16F1 melanoma cells causes an eNOS-dependent local burst of NO by the sinusoidal lining cells and hepatocytes in the periportal areas. [Copyright &y& Elsevier]

Within the tumor-stromal microenvironment a disrupted balance between matrix metalloproteinases (MMPs) and their inhibitors compromises the integrity of the extracellular matrix and promotes malignancy. Tissue inhibitors of metalloproteinases (TIMPs) have been linked to tumor suppression in studies of genetically altered tissue culture cells and in analyses of clinical specimens in situ. We generated transgenic mice as a model system to test the relationship between TIMP-1 levels in a host organ and susceptibility to experimentally targeted metastasis. Ectopically overexpressed TIMP-1 in the brain resulted in a tissue microenvironment with elevated protein levels of this natural MMP inhibitor. Metastatic challenge provided by lacZ-tagged fibrosarcoma cells permitted high-resolution analysis of metastatic load and pattern. We found that elevated host TIMP-1 imposed resistance to experimental metastasis of fibrosarcoma: In TIMP-1 overexpressing mice, brain metastases were significantly reduced by 75% compared to wild-type littermates. Our findings demonstrate that ectopic TIMP-1 expression efficiently exerts a suppressive effect on metastasizing tumor cells. [ABSTRACT FROM AUTHOR]

Alcohol and other drugs (AOD) use is a significant public health issue and is associated with high mortality and morbidity rates. Despite this, people who use drugs are often reluctant to seek care due to the lack of trauma-informed treatment and harm reduction treatment options, as well as experiences of stigma and discrimination in health services. Arguably, AOD education that is co-produced with people who use alcohol and drugs can enhance future health professionals' ability to practice in ways that support the needs of this population. This paper reports on a qualitative co-evaluation of a co-produced undergraduate nursing AOD subject. The AOD subject was co-planned, co-designed, co-delivered, and co-evaluated with experts by experience, who have a lived experience of substance dependence and work as advocates and peer workers. Following the delivery of the subject in 2021 and 2022, focus groups were undertaken with 12 nursing students. Focus group data indicate that the co-produced subject supported participants to understand and appreciate how stigma impacts on nursing care and how to recognize and undertake 'good' nursing care that was oriented to the needs of service users. Student participants noted that being co-taught by people who use drugs was particularly powerful for shifting their nursing perspectives on AOD use and nursing care and took learning beyond what could be understood from a book. Findings indicate that co-produced AOD education can shift nursing students' perceptions of AOD use by providing access to tacit knowledge and embodied equitable and collaborative relationships with people who use drugs., (© 2022 The Authors. International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd.)

Breastfeeding is the ideal infant feeding modality; however, the reality is some parents need or choose to use bottles to feed their infants. Parents who bottle-feed have been identified as not receiving adequate levels of bottle-feeding information and advice from health professionals. This study's aim was to explore nurses' knowledge of the components in the bottle-feeding act. Twenty-one nurses working in early parenting residential units participated in three focus groups. Three themes were identified relating to nurses' bottle-feeding knowledge: experience not evidence-based, it is hard to know what to advise, we will support whatever choice they make. The nurses identified a deficit in their knowledge, education and training related to the components of bottle-feeding. The nurses struggled with their interpretation of infant feeding policies and the provision of bottle-feeding information to parents. Nurses working in child and family health were motivated to inform, educate and enable parents to confidently make decisions concerning infant feeding. The healthcare system and the infant feeding policy drivers appear to have a mixed and at times negative impact on nurses' practice. Further research is required across a larger population of nurses.

Background: Nurses and midwives have a professional obligation to promote health and prevent disease, and therefore they have an essential role to play in vaccination. Despite this, some nurses and midwives have been found to take an anti-vaccination stance and promulgate misinformation about vaccines, often using Facebook as a platform to do so., Research Question: This article reports on one component and dataset from a larger study - 'the positives, perils and pitfalls of Facebook for nurses'. It explores the specific issue of nurses and midwives who take an anti-vaccination stance, deemed to be unprofessional by crossing professional boundaries and by providing medical information on Facebook that is not within their scope of practice., Participants: Data were collected via an online worldwide survey from nurse and midwife participants, distributed and 'snowballed' through relevant nursing and midwifery groups on Facebook. In total, 1644 Registered Nurses and Midwives, and Enrolled Nurses worldwide attempted the online survey. There were 1100 (66.9%) completed surveys and 54 partially (33.1%) completed surveys. Semi-structured interviews were also conducted online using Skype® with 17 participants in Australia., Ethical Considerations: Ethical processes and procedures have been adhered to relating to privacy, confidentiality and anonymity of the participants., Findings/results: A mixed-methods approach was used, including descriptive and content analysis of the quantitative survey data and thematic analysis of the qualitative interview data. The main theme 'blurred boundaries' was generated, which comprised three sub-themes: 'follow the science, 'abuse of power and erosion of trust' and 'the moral and ethical responsibility to safeguard public health'. The results offer an important and unique understanding of how nurses and midwives interpret the conduct of fellow health professionals as unprofessional and crossing the professional boundary if they used Facebook to promulgate anti-vaccination messages and/or give medical advice online., Conclusion: There are many positives and negatives for nurses and midwives associated with using Facebook for personal and professional communication, which is in keeping with the results of the larger study from which this article is taken. Professional behaviour is a key theme in the larger research as is the ethical construct of 'every act has a consequence'; however, in this article, the theme 'blurred boundaries' offers an overall understanding of how nurses and midwives interpret the behaviour of their colleagues who espouse anti-vaccination sentiment and/or give medical advice online that is outside their scope of practice and education.

Recovery-focused educational programmes have been implemented in mental health services in an attempt to transform care from a purely biomedical orientation to a more recovery-oriented approach. Mental health nurses have identified the need for enhancing their abilities and confidence in translating recovery knowledge into mental health nursing practice. However, recovery-focused educational programmes have not fully address nurses' learning needs. Therefore, this review synthesized the evidence of the effectiveness of recovery-focused educational programmes for mental health nurses. A systematic search of electronic databases and hand-searched references was conducted. It identified 35 programmes and 55 educational materials within 39 studies. Synthesizing the literature revealed three themes and nine subthemes. The first theme, a framework for understanding and supporting consumers' recovery, had four subthemes: consumers' involvement, multidisciplinary approach, profession-specific training, and performance indicators. The second theme, contents of educational materials, included the subthemes: knowledge development and recovery-focused care planning. The final theme, nurses' learning experiences, included the subthemes: understanding recovery, the positive effects of recovery-focused educational programmes, and implementation of recovery-oriented practices. Based on these findings, a mental health nursing recovery-focused educational programme framework is proposed. Further research should investigate the effectiveness of the framework, especially in relation to recovery-focused care planning and consumer and carer involvement in the development, delivery, participation, and evaluation of these educational programmes., (© 2021 John Wiley & Sons Australia, Ltd.)

Ensuring students develop person-centred practice for diverse groups of people across health care settings is an important outcome of undergraduate nursing education. This paper presents the development and evaluation of a learning innovation, an integrated virtual patient case study and complementary online resources for person-centred nursing practice. The virtual patient case study of an Australian Aboriginal woman diagnosed with breast cancer was integrated within four core subjects of a Bachelor of Nursing program, for a total of 600 second-year students. The evaluation of this learning strategy was encouraging. Students reported that the online learning activities were engaging, particularly due to the level of realism, their understanding of Aboriginal Peoples' healthcare needs increased, and they developed therapeutic communication skills, applicable in a variety of healthcare contexts. Staff concerns about student wellbeing when learning sensitive content online were unfounded. When carefully planned, a virtual patient case study and online learning resources can support students to enhance their person-centred nursing practice. Further evaluation, including student outcomes through assessment, is an important next step., (Copyright © 2021 Elsevier Ltd. All rights reserved.)