Hsa-miR-323a-3p functions as a tumor suppressor and targets STAT3 in neuroblastoma cells.

Background: Studies conducted in the last decades have revealed a role for the non-coding microRNAs (miRNAs) in cancer development and progression. Several miRNAs within the chromosome region 14q32, a region commonly deleted in cancers, are associated with poor clinical outcome in the childhood cancer neuroblastoma. We have previously identified miR-323a-3p from this region to be downregulated in chemotherapy treated neuroblastoma cells compared to pre-treatment cells from the same patients. Furthermore, in neuroblastoma tumors, this miRNA is downregulated in advanced stage 4 disease compared to stage 1-2. In this study, we attempt to delineate the unknown functional roles of miR-323a-3p in neuroblastoma. Methods: Synthetic miRNA mimics were used to overexpress miR-323a-3p in neuroblastoma cell lines. To investigate the functional roles of miR-323a-3p, cell viability assay, flow cytometry, reverse transcription-quantitative polymerase chain reaction, luciferase reporter assay and western blot were conducted on the neuroblastoma cell lines Kelly, SH-SY5Y and SK-N-BE(2)-C. Results: Ectopic expression of miR-323a-3p resulted in marked reduction of cell viability in Kelly, SH-SY5Y and SK-N-BE(2)-C by causing G1-cell cycle arrest in Kelly and SH-SY5Y and apoptosis in all the cell lines tested. Furthermore, mRNA and protein levels of signal transducer and activator of transcription 3 (STAT3) were reduced upon miR-323a-3p overexpression. A direct binding of the miR-323a-3p to the 3'UTR of STAT3 was experimentally validated by luciferase reporter assay, where miR-323a-3p reduced luminescent signal from full length STAT3 3'UTR luciferase reporter, but not from a reporter with mutation in the predicted seed sequence. Conclusions: miR-323a-3p inhibits growth of neuroblastoma cell lines through G1-cell cycle arrest and apoptosis, and the well-known oncogene STAT3 is a direct target of this miRNA.

Hospitality in dementia-friendly environments is significant to caregivers during hospitalisation of their loved ones. A qualitative study.

AIM AND OBJECTIVES: To explore what is meaningful to caregivers in relation to a dementia-friendly environment during hospitalisation of their loved ones with dementia or cognitive impairment. BACKGROUND: Implementation of dementia-friendly initiatives and person-centred care approach have shaped the political agenda within Danish society. Patients with dementia or cognitive impairment and their accompanying caregivers are challenged when admitted to hospital. During hospitalisation, caregivers find themselves in a vulnerable state of mind. Thus, the implementation of a dementia-friendly environment and adherence to person-centred care in hospital settings leaves room for improvement. METHODS: This study was guided by a qualitative and explorative approach. Data were collected through 17 semi-structured interviews with caregivers at a subacute neurological ward. Thematic analysis was employed to interpret data. The study reports according to the COREQ checklist. RESULTS: The following three themes were identified: 1) Being a watchful bystander. 2) Visiting an undefined and foreign environment. 3) Longing for kindness. CONCLUSION: Hospitality expressed by staff towards caregivers is significant in allowing caregivers to experience hospital environments as "friendly." Dementia-friendly environments embrace existential aspects that go far beyond physical spaces; hence, experiences of kind acts shape caregivers' sense of safety and comfort during hospitalisation. Hospitality is an essential part of nursing in dementia care because caregivers are contextually vulnerable. Our study sheds new light on the provision of person-centred care to people with dementia and their families in healthcare. RELEVANCE TO CLINICAL PRACTICE: Nurses need to be aware that caregivers experience vulnerability and to involve caregivers in the care provided for patients with dementia. We recommend that a permanent contact person be appointed to follow patients throughout their admission period. Furthermore, systematic interventions focusing on phenomena such as hospitality and kindness may serve to form a person-centred clinical culture; an issue that warrants further investigation.

Wearables in real life: A qualitative study of experiences of people with epilepsy who use home seizure monitoring devices.

OBJECTIVE: To explore the experiences of people with epilepsy using wearables for home seizure monitoring. METHODS: Nine people with epilepsy participated in eighteen semistructured individual interviews before and after home monitoring with wearable seizure monitoring equipment. An open-ended interview guide was used to encourage the participants to elaborate on their thoughts and experiences. Interviews were analyzed using a three-level process inspired by the philosopher Max van Manen. RESULTS: The overall findings illustrate that patients experienced being placed in the spotlight when wearing wearables. The meaning of being in this spotlight is reflected in three themes: Becoming vulnerable through exposure, Standing alone while being with others, and Having a renewed life situation. The analysis and interpretation showed that although the participants expressed readiness to use the wearables, they were less willing to do so after a few days of monitoring. The visibility of the devices influenced how they experienced themselves and were perceived by others. CONCLUSION: For people with epilepsy, wearables are more than just technical tools; they have a significant existential impact on everyday life. Wearables spotlight the epilepsy condition, and this causes people with epilepsy to experience an existential disruption, as they experience being exposed and vulnerable. This results in a renewed way of perceiving oneself. Nevertheless, wearables also validate epilepsy symptoms, thereby reducing the uncertainty related to epilepsy.

User perspectives and preferences regarding a mobile health cough application: A qualitative study during the coronavirus disease pandemic in Denmark.

INTRODUCTION: Health care systems worldwide are currently facing major challenges because of the coronavirus disease pandemic. When individuals experience coronavirus disease symptoms, they often have to decide whether to seek health care services and render themselves vulnerable to infection or stay home and monitor their condition. Coronavirus disease management strategies should aim to reduce transmission, promote disease control, and facilitate self-monitoring within the population. In this regard, mobile health technologies serve as supportive tools, and acquiring knowledge about user perspectives will facilitate the development and integration of coronavirus disease-related applications. Accordingly, this study aimed to examine user perspectives on applications that monitor coronavirus disease-related physical signs and identify discrepancies between user expectations and developer design perspectives within the Danish context. MATERIALS AND METHODS: A qualitative research design was adopted. Semi-structured telephone interviews were conducted to examine user expectations during the first wave of the coronavirus disease pandemic in April 2020. The theoretical framework, which was inspired by the concept of health literacy, was developed using a six-step thematic analytic approach. RESULTS: The analysis yielded two major themes that captured user experiences: (1) coronavirus disease-related applications may serve as digital tools that foster safety when physical signs are monitored and (2) the acceptability of coronavirus disease-related applications depends on the adoption of a personalised and user-friendly design.

Inhibitors of ribosome biogenesis repress the growth of MYCN-amplified neuroblastoma.

Abnormal increases in nucleolar size and number caused by dysregulation of ribosome biogenesis has emerged as a hallmark in the majority of spontaneous cancers. The observed ribosome hyperactivity can be directly induced by the MYC transcription factors controlling the expression of RNA and protein components of the ribosome. Neuroblastoma, a highly malignant childhood tumor of the sympathetic nervous system, is frequently characterized by MYCN gene amplification and high expression of MYCN and c-MYC signature genes. Here, we show a strong correlation between high-risk disease, MYCN expression, poor survival, and ribosome biogenesis in neuroblastoma patients. Treatment of neuroblastoma cells with quarfloxin or CX-5461, two small molecule inhibitors of RNA polymerase I, suppressed MycN expression, induced DNA damage, and activated p53 followed by cell cycle arrest or apoptosis. CX-5461 repressed the growth of established MYCN-amplified neuroblastoma xenograft tumors in nude mice. These findings suggest that inhibition of ribosome biogenesis represent new therapeutic opportunities for children with high-risk neuroblastomas expressing high levels of Myc.

Global responses of Aliivibrio salmonicida to hydrogen peroxide as revealed by microarray analysis.

Aliivibrio salmonicida causes "cold-water vibriosis" (or "Hitra disease") in fish, including marine-reared Atlantic salmon. During development of the disease the bacterium will encounter macrophages with antibacterial activities such as production of damaging reactive oxygen species (ROS). To defend itself the bacterium will presumably start producing detoxifying enzymes, reducing agents, and proteins involved in DNA and protein repair systems. Even though responses to oxidative stress are well studied for a few model bacteria, little work has been done in general to explain how important groups of pathogens, like members of the Vibrionaceae family, can survive at high levels of ROS. We have used bioinformatic tools and microarray to study how A. salmonicida responds to hydrogen peroxide (H(2)O(2)). First, we used the recently published genome sequence to predict potential binding sites for OxyR (H(2)O(2) response regulator). The computer-based search identified OxyR sites associated with 20 single genes and 8 operons, and these predictions were compared to experimental data from Northern blot analysis and microarray analysis. In general, OxyR binding site predictions and experimental results are in agreement. Up- and down regulated genes are distributed among all functional gene categories, but a striking number of ≥2 fold up regulated genes encode proteins involved in detoxification and DNA repair, are part of reduction systems, or are involved in carbon metabolism and regeneration of NADPH. Our predictions and -omics data corroborates well with findings from other model bacteria, but also suggest species-specific gene regulation.