bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroprotective effect of diosgenin in a mouse model of diabetic peripheral neuropathy involves the Nrf2/HO-1 pathway
Authors: Leng Jinhong , Li Xiaohua , Tian He , Liu Chang , Guo Yining , Zhang Su , Chu Yang , Li Jian , Wang Ying , Zhang Ling
Published: April 2020

Background

Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes. Diosgenin is a natural steroidal saponin with a variety of beneficial effects, including antidiabetic effects, and is a raw material for the synthesis of carrier hormones. In our study, we aimed to assess the antioxidant effects of diosgenin in diabetic mice.

Methods

Male C57 mice were fed a high-fat diet for 8 weeks and intraperitoneally injected with streptozotocin (STZ) at a dose of 100 mg/kg for 2 consecutive days. Eligible mice were divided into the normal control group (CON), diabetic group (DM), low-dose diosgenin (50 mg/kg) group (DIO50) and high-dose diosgenin (100 mg/kg) group (DIO100). Treatment was started 6 weeks after the induction of diabetes by STZ and continued for 8 weeks. Blood sugar and body weight were monitored dynamically. The behavioural effects of diosgenin were detected by a hot tail immersion test and paw tactile responses. HE staining was used to evaluate edema and degeneration of the sciatic nerve. The levels of SOD, MDA and GPx were tested according to the instructions of the respective kits. The levels of Nrf2, HO-1 and NQO1 were detected by immunofluorescence and Western blotting. Statistical analysis was performed using SPSS, andP < 0.05 was considered statistically significant.

Results

Diosgenin decreased the blood glucose levels and increased the body weight of diabetic mice. There was a significant increase in the tail withdrawal latency of diabetic animals, and mechanical hyperalgesia was significantly alleviated after diosgenin treatment. Histopathological micrographs of HE-stained sciatic nerves showed improvement after diosgenin treatment. Diosgenin attenuated the level of MDA but increased the activities of SOD and GPx. Diosgenin increased the expression of Nrf2, HO-1 and NQO1.

Conclusions

Our results demonstrate that diosgenin can ameliorate behavioural and morphological changes in DPN by reducing oxidative stress. The Nrf2/HO-1 signalling pathway was involved in its neuroprotective effects.
Inter-professional collaboration of nurses and midwives with physicians and associated factors in Jimma University specialized teaching hospital, Jimma, south West Ethiopia, 2019: cross sectional study
Authors: Melkamu Eneyew , Woldemariam Solomon , Haftu Abera
Published: April 2020

Background

Inter-professional collaboration between professionals is crucial in health care where most of the activities are undertaken in a team. One of these collaborations is the collaboration of nurses and midwives with physicians. The main objective of this study was to assess interprofessional collaboration of nurses and midwives with physicians and associated factors at Jimma University specialized teaching hospital from March 20 to April 8, 2019.

Methods

An institution-based cross-sectional study was conducted among 358 nurses and 52 midwives who are working in Jimma University Specialized teaching hospital using a structured self-administered questionnaire. Study units were selected by simple random sampling using the lottery method. The result was summarized using descriptive statistics and statements. The level of significance was set at ap < 0.05.

Result

The overall response rate was 99.76%. Around two-third, 66.7% (n = 273) of participants had a satisfactory inter-professional collaboration with physicians and 238 (58.2%) had good relationship with physicians. Again 234 (57.2%) of participants had a favorable attitude towards interprofessional collaboration with physicians. Moreover, statistical significance was obtained on the relationship of participants with physicians (p = 0.000), the experience of disruptive behavior (p = 0.000), attitude towards interprofessional collaboration with physicians (p = 0.000) and occupational status (p = 0.001).

Conclusion

The majority of the participants had a satisfactory inter-professional collaboration with physicians and four of the many possible factors under consideration were finally found statistically significant. Again, it was revealed that nurses and midwives did not significantly differ in their inter-professional collaboration with physicians.
Evaluation of a co-produced delirium awareness programme for undergraduate nursing students in Northern Ireland: a pre-test/post-test study
Authors: Mitchell Gary , McVeigh Clare , Carlisle Susan , Brown-Wilson Christine
Published: April 2020

Background

Delirium is recognised internationally as a common disorder that causes acute deterioration in a person’s cognitive abilities. Healthcare professionals play a key role in the early identification and management of delirium and effective education can support timely recognition and treatment. There is currently a lack of research exploring the delirium education provided to undergraduate nursing students. The aim of this study was to evaluate the effectiveness of a co-produced delirium awareness programme on undergraduate nursing students in Northern Ireland.

Methods

The intervention was a 2-h delirium workshop, delivered in April 2019, to a convenience sample of year one undergraduate nursing students (n = 206) completing a BSc Honours Nursing degree programme in a Northern Ireland University. The workshop focused on four core elements: defining delirium, reflecting on practice, recognition of delirium and management of delirium. Participants completed a 35-item true-false Delirium Knowledge Questionnaire (DKQ) at baseline and post intervention using Socrative, a cloud-based student response system. In addition, students also completed a short questionnaire at baseline and post-workshop, designed by the authors, to ascertain perceived confidence about caring for people with delirium. Data were analysed using paired t-tests and descriptive statistics.

Results

In the DKQ, Scores were normally distributed around the mean at baseline (71.89%) and post intervention (81.89%). Students improved across all three core areas in the post-test questionnaire, demonstrating improvements in knowledge about symptoms of delirium (7.32% increase), causes and risk factors of delirium (17.91% increase) and management of delirium (5.72% increase). In relation to perceived confidence, students reported a 60.20% increase in confidence related to recognition of delirium, a 49.51% increase in relation to delirium management and a 45.04% increase their ability to communicate about delirium. Both questionnaires were statistically significant (P < 0.01).

Conclusions

A 2-h workshop on delirium improved first year student nurse knowledge about delirium. Nursing students expressed that this approach to delirium education enabled collective thinking about how knowledge could be transferred into individual practises. Students also stated that learning incorporating the voice of the person who has experienced delirium, was an effective and powerful way to deliver education.
Nudging New York: adaptive models and the limits of behavioral interventions to reduce no-shows and health inequalities
Authors: Ruggeri Kai , Folke Tomas , Benzerga Amel , Verra Sanne , Büttner Clara , Steinbeck Viktoria , Yee Susan , Chaiyachati Krisda
Published: April 2020

Background

Missed healthcare appointments (no-shows) are costly and operationally inefficient for health systems. No-show rates are particularly high for vulnerable populations, even though these populations often require additional care. Few studies on no-show behavior or potential interventions exist specifically for Federally Qualified Health Centers (FQHCs), which care for over 24 million disadvantaged individuals in the United States. The purpose of this study is to identify predictors of no-show behavior and to analyze the effects of a reminder intervention in urban FQHCs in order to design effective policy solutions to a protracted issue in healthcare.

Methods

This is a retrospective observational study using electronic medical record data from 11 facilities belonging to a New York City-based FQHC network between June 2017 to April 2018. This data includes 53,149 visits for 41,495 unique patients. Seven hierarchical generalized linear models and generalized additive models were used to predict no-shows, and multiple regression models evaluated the effectiveness of a reminder. All analyses were conducted in R.

Results

The strongest predictor of no-show rates in FQHCs is whether or not patients are assigned to empaneled providers (z = − 91.45, p < 10− 10), followed by lead time for appointments (z = 23.87, p < 10− 10). These effects were fairly stable across facilities. The reminder had minimal effects on no-show rates overall (No show rate before: 41.6%, after: 42.1%). For individuals with appointments before and after the reminder, there was a small decrease in no-shows of 2%.

Conclusions

The limited effects of the reminder intervention suggest the need for more personalized behavioral interventions to reduce no-shows. We recommend that these begin with increasing the use of empaneled providers for preventive care appointments and reducing the lag time between setting the appointment and the actual date of the appointment, at least for individuals with a high rate of no-show. By complementing these with low-intensity, low-cost behavioral interventions, we would expect greater impacts for improved access to care, contributing to the well-being of vulnerable populations.
Measuring patient experiences in a Children’s hospital with a medical clowning intervention: a case-control study
Authors: Karisalmi Nina , Mäenpää Katja , Kaipio Johanna , Lahdenne Pekka
Published: April 2020

Background

Because the healthcare sector is shifting to a customer-oriented approach, it is important to understand experiences of children as users of healthcare services. So far, studies that measure the influence of medical clowning on patient experiences are scarce. This study aims to measure experiences of children and their parents during day-surgery in hospital setting.

Methods

A case-control study was conducted in a large Finnish children’s hospital. Seventy children aged 4–17 years coming for a minor operative procedure including pre-operative cannula insertion prior to surgery were included. Thirty-eight children were exposed to the medical clowning intervention and 32 children (the reference group) did not receive exposure to medical clowning. A novel digital survey tool was used to measure patient experiences before and after the insertion of a venous cannula needed for anaesthesia. The children were asked about their emotions, anxiety levels, the pain from the cannula insertion and the best and worst things about the hospital. The parents were asked about their emotions, expectations and the fluency of the procedure and the hospital day.

Results

Before the procedure, 32% or 36% of the children in the intervention group and 44% or 28% of those in the reference group expressed positive or neutral emotions, respectively. After the procedure, 76% or 63% of children in the intervention group or reference group, respectively, expressed positive emotions. The intervention group rated the medical clowns as the best aspect of the hospital day. Both groups reported that the best aspects of the hospital day were related to the nurses and food and the worst were related to waiting and pain. Most commonly the parents felt uncertainty, anxiety or calmness before the procedure and relief afterwards. Their expectations towards the procedure related to its success and the certainty of the diagnosis.

Conclusions

The results show a trend towards more positive emotions in children with exposure to medical clowning. The digital survey tool was suitable for gathering information about the experiences of children and their parents. Information on emotions and expectations of children and parents during a procedure is useful when improving the quality of healthcare services.

Trial registration

Current Controlled Trials NCT04312217, date of registration 17.03.2020.

Retrospectively registered.
Evaluating the feasibility of implementing a Telesleep pilot program using two-tiered external facilitation
Authors: Rattray Nicholas A. , Khaw Andrew , McGrath Mackenzie , Damush Teresa M. , Miech Edward J. , Lenet Adam , Stahl Stephanie , Ferguson Jared , Myers Jennifer , Guenther David , Homoya Barbara J. , Bravata Dawn M.
Published: April 2020

Background

Obstructive sleep apnea (OSA) can negatively impact patients’ health status and outcomes. Positive airway pressure (PAP) reverses airway obstruction and may reduce the risk of adverse outcomes. Remote monitoring of PAP (as opposed to in-person visits) may improve access to sleep medicine services. This study aimed to evaluate the feasibility of implementing a clinical program that delivers treatment for OSA through PAP remote monitoring using external facilitation as an implementation strategy.

Methods

Participants included patients with OSA at a Veteran Affairs Medical Center (VAMC). PAP adherence and clinical disease severity on treatment (measured by the apnea hypopnea index [AHI]) were the preliminary effectiveness outcomes across two delivery models: usual care (in-person) and Telehealth nurse-delivered remote monitoring. We also assessed visit duration and travel distance. A prospective, mixed-methods evaluation examined the two-tiered external facilitation implementation strategy.

Results

The pilot project included N = 52 usual care patients and N = 38 Telehealth nurse-delivered remote monitoring patients. PAP adherence and disease severity were similar across the delivery modalities. However, remote monitoring visits were 50% shorter than in-person visits and saved a mean of 72 miles of travel (median = 45.6, SD = 59.0, mode = 17.8, range 5.4–220). A total of 62 interviews were conducted during implementation with a purposive sample of 12 clinical staff involved in program implementation. Weekly external facilitation delivered to both front-line staff and supervisory physicians was necessary to ensure patient enrollment and treatment. Synchronized, “two-tiered” facilitation at the executive and coordinator levels proved crucial to developing the clinical and administrative infrastructure to support a PAP remote monitoring program and to overcome implementation barriers.

Conclusions

Remote PAP monitoring had similar efficacy to in-person PAP services in this Veteran population. Although external facilitation is a widely-recognized implementation strategy in quality improvement projects, less is known about how multiple facilitators work together to help implement complex programs. Two–tiered facilitation offers a model well-suited to programs where innovations span disciplines, disrupt professional hierarchies (such as those between service chiefs, clinicians, and technicians) and bring together providers who do not know each other, yet must collaborate to improve access to care.
Temporal trends in emergency department volumes and crowding metrics in a western Canadian province: a population-based, administrative data study
Authors: Rowe Brian H. , McRae Andrew , Rosychuk Rhonda J.
Published: April 2020

Background

Emergency Department (ED) crowding is a pervasive problem, yet there have been few comparisons of the extent of, and contributors to, crowding among different types of EDs. The study quantifies and compares crowding metrics for 16 high volume regional, urban and academic EDs in one Canadian province.

Methods

The National Ambulatory Care Reporting System (NACRS) provided ED presentations by adults to 16 high volume Alberta EDs during April 2010 to March 2015 for this retrospective cohort study. Time to physician initial assessment (PIA), length of stay (LOS) for discharges and admissions were grouped by start hour of presentation and facility. Multiple crowding metrics were created by taking the means, medians (PIA-M, LOS-M), and 90th percentiles of the hourly, ED-specific values. Similarly, proportion left against medical advice (LAMA) and proportion left without being seen (LWBS) were day and ED aggregated. Calculated based on the start of the presentation and the facility and for PIA and LOS. The mean, median, and 90th percentiles for the date and time ED-specific metrics for PIA and LOS were obtained. Summary statistics were used to describe crowding metrics.

Results

There were 3,925,457 presentations by 1,420,679 adults. The number of presentations was similar for each sex and the mean age was 46 years. Generally, the three categories of EDs had similar characteristics; however, urban and academic/teaching EDs had more urgent triage scores and a higher percentage of admissions than regional EDs. The median of the PIA-M metric was 1 h23m across all EDs. For discharges, the median of the LOS-M metric was 3h21m whereas the median of the LOS-M metric for admissions was 10h08m. Generally, regional EDs had shorter times than urban and academic/teaching EDs. The median daily LWBS was 3.4% and the median daily LAMA was about 1%.

Conclusions

Emergency presentations have increased over time, and crowding metrics vary considerably among EDs and over the time of day. Academic/teaching EDs generally have higher crowding metrics than other EDs and urgent action is required to mitigate the well-known consequences of ED crowding.
Number of consulting medical institutions and risk of polypharmacy in community-dwelling older people under a healthcare system with free access: a cross-sectional study in Japan
Authors: Suzuki Toshiki , Iwagami Masao , Hamada Shota , Matsuda Tomoyuki , Tamiya Nanako
Published: April 2020

Background

Under the Japanese free access healthcare system, patients are allowed to consult multiple medical institutions (including clinics and hospitals for general or specialist consultation) without primary care referral. This potentially increases the risk of polypharmacy. We examined the association between the number of consulting medical institutions and polypharmacy under a healthcare system with free access.

Methods

Via a self-administered questionnaire, we identified people aged ≥65 years with ≥1 disease and  ≥1 consulting medical institution in a Japanese city in 2016. The exposure of interest was the number of consulting medical institutions (1, 2, or ≥3) and the outcome was polypharmacy (use of ≥6 types of drugs). We performed a multivariate logistic regression analysis, adjusting for age, sex, household economy, and the number and type of comorbidities. To minimize confounding effects, we also performed propensity-score-matched analysis, categorizing patients into two groups: 1 and  ≥2 consulting medical institutions.

Results

Of 993 eligible individuals (mean (standard deviation) age: 75.1 (6.5) years, men: 52.6%), 15.7% (156/993) showed polypharmacy. Proportions of polypharmacy were 9.7% (50/516), 16.6% (55/332), and 35.2% (51/145) for people who consulted 1, 2, and  ≥3 medical institutions, respectively. Relative to people who consulted 1 medical institution, adjusted odds ratios (95% confidence intervals) for polypharmacy were 1.50 (0.94–2.37) and 3.34 (1.98–5.65) for those who consulted 2 and  ≥3 medical institutions, respectively. In propensity score matching, of 516 and 477 patients who consulted 1 and  ≥2 medical institutions, 307 pairs were generated. The proportion of polypharmacy was 10.8% (33/307) and 17.3% (53/307), respectively (P = 0.020). The odds ratio for polypharmacy (≥2 vs. 1 consulting medical institution) was 1.73 (95% confidence interval 1.09–2.76).

Conclusions

Patients who consulted more medical institutions were more likely to show polypharmacy. The results could encourage physicians and pharmacists to collect medication information more actively and conduct appropriate medication reviews. Strengthening primary care is needed to address the polypharmacy issue, especially in countries with healthcare systems with free access.
Patient satisfaction with remote monitoring of cardiac implantable electronic devices: the Valiosa questionnaire
Authors:   On behalf of the VALIOSA study group, Ruiz Díaz Miguel A. , Egea García Marta , Muñoz Aguilera Roberto , Viñolas Prat Xavier , Silvestre García Jorge , Álvarez Orozco María , Martínez Ferrer José
Published: April 2020

Background

Remote monitoring of cardiac implantable electronic devices (CIEDs) has demonstrated substantial benefits. Treatment guidelines have therefore endorsed its use and is being increasingly adopted in the clinical setting, but the level of satisfaction they convey remains still unknown. We developed and validated a questionnaire to measure patient satisfaction with remote monitoring using Medtronic CareLink® Network and assessed its internal reliability and dimensional validity.

Methods

After a thorough literature review, cognitive debriefing of 18 patients, and an expert panel discussion, a 30-item instrument was proposed and grouped into 5 dimensions (items): 1- Information on cardiac condition (3), 2- Device convenience (3), 3- Transmission process (6), 4- Satisfaction with medical monitoring (8), and 5- General opinions (10). Correlation with the visual analog scale (VAS), overall health related quality of life (HRQoL) measured by the EuroQoL-5D accompanied by the VAS as well as with the Medical Outcomes Study (MOS) SF-36 were assessed. Psychometric properties, exploratory factor analysis and a second order confirmatory factor analysis (a hierarchical CFA with a general common factor explaining the relations between the first order common factors, See Figure 1) were estimated. Models were assessed based on item loading size, sign and statistical significance, and goodness-of-fit statistics.

Results

A total of 186 patients (77% male) with a mean age of 66.03 (SD = 13.94) years were assessed. 48% had implantable cardioverter-defibrillators, 24% had pacemakers, and 29% had cardiac resynchronization therapy devices. An overall Cronbach’s α = 0.893 was achieved, with acceptable reliabilities for isolated dimensions. Correlations with corresponding VAS scales were meaningful and significant (p < 0.01). The second order factor solution yielded good goodness-of-fit indexes (χ2/df = 1.44, CFI = 0.96, TLI = 0.95, RMSEA = 0.05). Satisfaction with remote monitoring was not related to HRQoL (r < 0.05), except for the correlation between the SF-36 mental component and the information on cardiac condition dimension (r = 0.263, p < 0.001).

Conclusions

The 30-item questionnaire showed good reliability and validity to assess satisfaction with remote monitoring in patients with CIEDs.
Moving enhanced recovery after surgery from implementation to sustainability across a health system: a qualitative assessment of leadership perspectives
Authors: Gramlich Leah , Nelson Gregg , Nelson Alison , Lagendyk Laura , Gilmour Loreen E. , Wasylak Tracy
Published: April 2020

Background

Knowledge Translation evidence from health care practitioners and administrators implementing Enhanced Recovery After Surgery (ERAS) care has allowed for the spread and scale of the health care innovation. There is a need to identify at a health system level, what it takes from a leadership perspective to move from implementation to sustainability over time. The purpose of this research was to systematically synthesize feedback from health care leaders to inform further spread, scale and sustainability of ERAS care across a health system.

Methods

Alberta Health Services (AHS) is the largest Canadian health system with approximately 280,000 surgeries annually at more than 50 surgical sites. In 2013 to 2014, AHS used a structured approach to successfully implement ERAS colorectal guidelines at six sites. Between 2016 and 2018, three of the six sites expanded ERAS to other surgical areas (gynecologic oncology, hepatectomy, pancreatectomy/Whipple’s, and cystectomy). This research was designed to explore and learn from the experiences of health care leaders involved in the AHS ERAS implementation expansion (eg. surgical care unit, hospital site or provincial program) and build on the model for knowledge mobilization develop during implementation. Following informed consent, leaders were interviewed using a structured interview guide. Data were recorded, coded and analyzed qualitatively through a combination of theory-driven immersion and crystallization, and template coding using NVivo 12.

Results

Forty-four individuals (13 physician leaders, 19 leading clinicians and hospital administrators, and 11 provincial leaders) were interviewed. Themes were identified related to Supportive Environments including resources, data, leadership; Champion and Nurse coordinator role; and Capacity Building through change management, education, and teams. The perception and role of leaders changed through initiation and implementation, spread, and sustainability. Barriers and enablers were thematically aligned relative to outcome assessment, consistency of implementation, ERAS care compliance, and the implementation of multiple guidelines.

Conclusions

Health care leaders have unique perspectives and approaches to support spread, scale and sustainability of ERAS that are different from site based ERAS teams. These findings inform us what leaders need to do or need to do differently to support implementation and to foster spread, scale and sustainability of ERAS.
Violence and aggression in psychiatric inpatient care in Sweden: a critical incident technique analysis of staff descriptions
Authors: Pelto-Piri Veikko , Warg Lars-Erik , Kjellin Lars
Published: April 2020

Background

Violence towards staff working in psychiatric inpatient care is a serious problem. The aim of the present study was to explore staff perspectives of serious violent incidents involving psychiatric inpatients through the following research questions: Which factors contributed to violent incidents, according to staff? How do staff describe their actions and experiences during and after violent incidents?

Methods

We collected data via a questionnaire with open-ended questions, and captured 283 incidents reported by 181 staff members from 10 inpatient psychiatric wards in four different regions. We used the Critical Incident Technique to analyse the material. Our structural analysis started by structuring extracts from the critical incidents into descriptions, which were grouped into three chronological units of analyses: before the incident, during the incident and after the incident. Thereafter, we categorised all descriptions into subcategories, categories and main areas.

Results

Staff members often attributed aggression and violence to internal patient factors rather than situational/relational or organisational factors. The descriptions of violent acts included verbal threats, serious assault and death threats. In addition to coercive measures and removal of patients from the ward, staff often dealt with these incidents using other active measures rather than passive defence or de-escalation. The main effects of violent incidents on staff were psychological and emotional. After violent incidents, staff had to continue caring for patients, and colleagues provided support. Support from managers was reported more rarely and staff expressed some dissatisfaction with the management.

Conclusions

As a primary prevention effort, it is important to raise awareness that external factors (organisational, situational and relational) are important causes of violence and may be easier to modify than internal patient factors. A secondary prevention approach could be to improve staff competence in the use of de-escalation techniques. An important tertiary prevention measure would be for management to follow up with staff regularly after violent incidents and to increase psychological support in such situations.
LBX2-AS1 up-regulated by NFIC boosts cell proliferation, migration and invasion in gastric cancer through targeting miR-491-5p/ZNF703
Authors: Xu Gang , Zhang Yan , Li Na , Wu Yanling , Zhang Jinbiao , Xu Rui , Ming Hui
Published: April 2020

Background

The crucial role of long non-coding RNAs (lncRNAs) has been certified in human cancers. The lncRNAs with abnormal expressions could act as tumor inhibitors or oncogenes in the advancement of tumors. LBX2-AS1 was once reported to accelerate esophageal squamous cell carcinoma. Nonetheless, its function in gastric cancer (GC) remained a riddle.

Methods

RT-qPCR was used to examine the expression of NFIC/LBX2-AS1/miR-491-5p/ZNF703 in GC cell lines. The functions of LBX2-AS1 in GC were appraised by colony formation, EdU, flow cytometry analysis, transwell and wound healing assays. Luciferase reporter, ChIP and RNA pull down assays were utilized to evaluate the interactions among genes.

Results

LBX2-AS1 was up-regulated in GC cell lines. Knockdown of LBX2-AS1 repressed the proliferative, migratory, and invasive abilities of GC cells. Moreover, LBX2-AS1 was transcriptionally activated by NFIC. And LBX2-AS1 could bind with miR-491-5p. Besides, miR-491-5p depletion or ZNF703 upregulation could counteract the repressing effects of LBX2-AS1 silence on GC progression.

Conclusion

In a word, LBX2-AS1 up-regulated by NFIC promoted GC progression via targeting miR-491-5p/ZNF703, implying LBX2-AS1 was an underlying treatment target for GC patients.
A long non-coding RNA LINC00461-dependent mechanism underlying breast cancer invasion and migration via the miR-144-3p/KPNA2 axis
Authors: Zhang Qiang , Jin Xiaoyan , Shi Wenbiao , Chen Xin , Pang Wenyang , Yu Xiaodong , Yang Linjun
Published: April 2020

Background

The purpose of this study was to explore the regulatory mechanism of the long non-coding RNA (lncRNA) LINC00461 underlying the breast cancer invasion and migration via the miR-144-3p/KPNA2 axis.

Methods

Bioinformatics methods were applied to screen differentially expressed mRNAs, miRNAs and lncRNAs for construction of a competing endogenous RNA (ceRNA) network. LINC00461, KPNA2 and miR-144-3p were identified, and KPNA2 was predicted to be a target of miR-144-3p and significantly correlated with breast cancer prognosis. To make the findings more convincible, we used qRT-PCR to detect the expression levels of LINC00461 and miR-144-3p in breast cancer cells, and conducted western blot to determine KPNA2 protein level. Then, RIP was performed to assess the combination between miR-144-3p and LINC00461 or KPNA2, and dual-luciferase reporter assay was used to validate the targeted relationship between miR-144-3p and KPNA2. Furthermore, Transwell was employed for the examination of cell invasion and migration in breast cancer.

Results

LINC00461 was predicted to regulate KPNA2 through sponging miR-144-3p as revealed by the ceRNA network. Besides, LINC00461 and KPNA2 were found to be remarkably highly-expressed in breast cancer cells, while miR-144-3p was poorly-expressed. Silencing LINC00461 could promote miR-144-3p expression, thus inhibiting cell invasion and migration. In addition, KPNA2 was confirmed to be a direct target of miR-144-3p. Silencing miR-144-3p or overexpressing KPNA2 could reverse the inhibitory effect of LINC00461 silencing on cell invasion and migration in breast cancer.

Conclusion

LINC00461 promoted the expression of KPNA2 by competitively binding to miR-144-3p, thereby promoting the invasion and migration of breast cancer cells.
Depleted circulatory complement-lysis inhibitor (CLI) in childhood cerebral malaria returns to normal with convalescence
Authors: Abah Samuel Eneọjọ , Burté Florence , Howell Steven A. , Lagunju Ikeoluwa , Shokunbi Wuraola A. , Wahlgren Mats , Sodeinde Olugbemiro , Brown Biobele J. , Holder Anthony A. , Fernandez-Reyes Delmiro
Published: April 2020

Background

Cerebral malaria (CM), is a life-threatening childhood malaria syndrome with high mortality. CM is associated with impaired consciousness and neurological damage. It is not fully understood, as yet, why some children develop CM. Presented here is an observation from longitudinal studies on CM in a paediatric cohort of children from a large, densely-populated and malaria holoendemic, sub-Saharan, West African metropolis.

Methods

Plasma samples were collected from a cohort of children with CM, severe malarial anaemia (SMA), uncomplicated malaria (UM), non-malaria positive healthy community controls (CC), and coma and anemic patients without malaria, as disease controls (DC). Proteomic two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry were used in a discovery cohort to identify plasma proteins that might be discriminatory among these clinical groups. The circulatory levels of identified proteins of interest were quantified by ELISA in a prospective validation cohort.

Results

The proteome analysis revealed differential abundance of circulatory complement-lysis inhibitor (CLI), also known as Clusterin (CLU). CLI circulatory level was low at hospital admission in all children presenting with CM and recovered to normal level during convalescence (p < 0.0001). At acute onset, circulatory level of CLI in the CM group significantly discriminates CM from the UM, SMA, DC and CC groups.

Conclusions

The CLI circulatory level is low in all patients in the CM group at admission, but recovers through convalescence. The level of CLI at acute onset may be a specific discriminatory marker of CM. This work suggests that CLI may play a role in the pathophysiology of CM and may be useful in the diagnosis and follow-up of children presenting with CM.
The role of Neurotensin and its receptors in non-gastrointestinal cancers: a review
Authors: Nikolaou Stella , Qiu Shengyang , Fiorentino Francesca , Simillis Constantinos , Rasheed Shahnawaz , Tekkis Paris , Kontovounisios Christos
Published: April 2020

Background

Neurotensin, originally isolated in 1973 has both endocrine and neuromodulator activity and acts through its three main receptors. Their role in promoting tumour cell proliferation, migration, DNA synthesis has been studied in a wide range of cancers. Expression of Neurotensin and its receptors has also been correlated to prognosis and prediction to treatment.

Main body

The effects of NT are mediated through mitogen-activated protein kinases, epidermal growth factor receptors and phosphatidylinositol-3 kinases amongst others. This review is a comprehensive summary of the molecular pathways by which Neurotensin and its receptors act in cancer cells.

Conclusion

Identifying the role of Neurotensin in the underlying molecular mechanisms in various cancers can give way to developing new agnostic drugs and personalizing treatment according to the genomic structure of various cancers.
LC–MS-based multivariate statistical analysis for the screening of potential thrombin/factor Xa inhibitors from Radix Salvia Miltiorrhiza
Authors: Yang Yi-Yao , Wu Zhao-Yu , Zhang Hao , Yin Shi-Jun , Xia Fang-Bo , Zhang Qian , Wan Jian-Bo , Gao Jian-Li , Yang Feng-Qing
Published: April 2020

Background

The dry root and rhizome of Salvia miltiorrhiza Bunge, or Danshen, is a well-known traditional Chinese medicine with anticoagulant activity. Taking into account that thrombin (THR) and factor Xa (FXa) play crucial roles in the coagulation cascade, it is reasonable and meaningful to screening THR and/or FXa inhibitors from Danshen.

Methods

Four extracts [butanol (BA), ethyl acetate (EA) and remained extract (RE) from 75% ethanol extract, and water extract (WE)] of Danshen were prepared, and their THR/FXa inhibitory activities were assessed in vitro. Then, the active EA extract was further separated by silica-gel column chromatography (SC), and its fractions (SC1–SC5) were analyzed by LC–MS. The principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA) were employed for predicting the specific marker compounds. The chemical structures of targeted compounds were identified by LC–MS/MS and their interactions with THR/FXa were analyzed by the molecular docking analysis.

Results

Danshen EA extract showed strong activity against THR and FXa, and its fractions (SC1–SC5) exhibited obvious difference in inhibitory activity against these two enzymes. Furthermore, four marker compounds with potential THR/FXa inhibitory activity were screened by PCA and OPLS-DA, and were identified as cryptotanshinone, tanshinone I, dihydrotanshinone I and tanshinone IIA. The molecular docking study showed that all these four tanshinones can interact with some key amino acid residues of the THR/FXa active cavities, such as HIS57 and SER195, which were considered to be promising candidates targeting THR and/or FXa with low binding energy (< − 7 kcal mol−1).

Conclusions

LC–MS combined with multivariate statistical analysis can effectively screen potential THR/FXa inhibitory components in Danshen.
miR-615-3p promotes the epithelial-mesenchymal transition and metastasis of breast cancer by targeting PICK1/TGFBRI axis
Authors: Lei Bo , Wang Dandan , Zhang Ming , Deng Yuwei , Jiang Huijie , Li Yiwen
Published: April 2020

Background

Increasing evidence indicates that epithelial-mesenchymal transition (EMT) can be regulated by microRNAs (miRNAs). miR-615-3p was shown to be involved in tumor development. However, the role of miR-615-3p in the metastasis of breast cancer remains largely unknown.

Methods

The expression of miR-615-3p in breast cancer cells and tissues was assessed by qRT-PCR and situ hybridization assays. Effects of miR-615-3p on tumor metastasis were evaluated with experiments in vitro and mouse model. EMT markers were detected by western blot and immunofluorescence assays. Molecular mechanism of miR-615-3p in the regulation of breast cancer cell metastasis was analyzed by Western Blot, Co-immunoprecipitation, and Luciferase assay.

Results

In the present study, we found that miR-615-3p was significantly elevated in breast cancer cells and tissues, especially in those with metastasis. In breast cancer cell lines, stable overexpression of miR-615-3p was sufficient to promote cell motility in vitro, and pulmonary metastasis in vivo, accompanied by the reduced expression of epithelial markers and the increased levels of mesenchymal markers. Further studies revealed that the reintroduction of miR-615-3p increased the downstream signaling of TGF-β, the type I receptor (TGFBRI) by targeting the 3′-untranslated regions (3′-UTR) of PICK1. PICK1 inhibits the binding of DICER1 to Smad2/3 and the processing of pre-miR-615-3p to mature miR-615-3p in breast cancer cells, thus exerting a negative feedback loop.

Conclusions

Our data highlight an important role of miR-615-3p in the molecular etiology of breast cancer, and implicate the potential application of miR-615-3p in cancer therapy.
Serum exosomal microRNA-34a as a potential biomarker in epithelial ovarian cancer
Authors: Maeda Kazuya , Sasaki Hiroshi , Ueda Shoko , Miyamoto Shunsuke , Terada Shinichi , Konishi Hiromi , Kogata Yuhei , Ashihara Keisuke , Fujiwara Satoe , Tanaka Yoshimichi , Tanaka Tomohito , Hayashi Masami , Ito Yuko , Kondo Yoichi , Ochiya Takahiro , Ohmichi Masahide
Published: April 2020

Background

Ovarian cancer (OC) is a leading cause of cancer-related death in women, and thus an accurate diagnosis of the predisposition and its early detection is necessary. The aims of this study were to determine whether serum exosomal microRNA-34a (miR-34a) in ovarian cancer could be used as a potential biomarker.

Methods

Exosomes from OC patients’ serum were collected, and exosomal miRNAs were extracted. The relative expression of miR-34a was calculated from 58 OC samples by quantitative real-time polymerase chain reaction.

Results

Serum exosomal miR-34a levels were significantly increased in early-stage OC patients compared with advanced-stage patients. Its levels were significantly lower in patients with lymph node metastasis than in those with no lymph node metastasis. Furthermore, its levels in the recurrence group were significantly lower than those in the recurrence-free group.

Conclusions

Serum exosomal miR-34a could be a potential biomarker for improving the diagnostic efficiency of OC.
Acupressure to improve sleep quality of older people in residential aged care: a randomised controlled trial protocol
Authors: Hmwe Nant Thin Thin , Browne Graeme , Mollart Lyndall , Allanson Viv , Chan Sally Wai-Chi
Published: April 2020

Background

Sleep disturbance in older people is an important health issue that is associated with many other health problems. Effective interventions are required to address sleep problems in this group. Acupressure has been suggested as a potential therapeutic technique to improve sleep. The aim of this study is to evaluate the effects of an acupressure intervention on sleep quality, anxiety, depression, and quality of life among older persons in residential aged care facilities within an Australian context.

Methods/design

This is a randomised controlled trial with two parallel groups in a pre- and post-test study. Study participants will be older people living in residential aged care facilities. They will be assigned to intervention and control groups using computer-generated random numbers. The intervention group will receive 12-min acupressure three times per week for four consecutive weeks, applied on three acupoints: HT7, PC6, and SP6. The control group will receive only routine care. The primary outcome measure is sleep quality, and secondary outcomes include anxiety, depression, and quality of life. Data will be collected before the intervention, immediately after the end of the intervention, and 2 weeks after the intervention.

Discussion

This study targets a poorly met healthcare need of older people who are experiencing sleep disturbance and its negative consequences. To the researchers’ knowledge, this is the first study evaluating acupressure in an Australian aged care context, using specific acupoints and a standardised acupressure protocol. If the results show positive outcomes, acupressure could be used to manage sleep disturbances for older people in the Australian context as well as in the global ageing population. This will contribute to reducing negative consequences of sleep disturbance and use of sleep medications.

Trial registration

Australian New Zealand Clinical Trials Registry: ACTRN12619000262101. Registered on 20 February 2019.
Roles of the HUWE1 ubiquitin ligase in nervous system development, function and disease
Authors: Giles Andrew C. , Grill Brock
Published: April 2020

Huwe1 is a highly conserved member of the HECT E3 ubiquitin ligase family. Here, we explore the growing importance of Huwe1 in nervous system development, function and disease. We discuss extensive progress made in deciphering how Huwe1 regulates neural progenitor proliferation and differentiation, cell migration, and axon development. We highlight recent evidence indicating that Huwe1 regulates inhibitory neurotransmission. In covering these topics, we focus on findings made using both vertebrate and invertebrate in vivo model systems. Finally, we discuss extensive human genetic studies that strongly implicate HUWE1 in intellectual disability, and heighten the importance of continuing to unravel how Huwe1 affects the nervous system.
Habitat suitability modelling to assess the introductions of Aedes albopictus (Diptera: Culicidae) in the Netherlands
Authors: Ibáñez-Justicia Adolfo , Alcaraz-Hernández Juan Diego , van Lammeren Ron , Koenraadt Constantianus J. M. , Bergsma Aldo , Delucchi Luca , Rizzoli Annapaola , Takken Willem
Published: April 2020

Background

In the Netherlands, Aedes albopictus has been found each year since 2010 during routine exotic mosquito species surveillance at companies that import used tires. We developed habitat suitability models to investigate the potential risk of establishment and spread of this invasive species at these locations.

Methods

We used two methodologies: first, a species distribution model based on the maximum entropy modelling approach (MaxEnt) taking into consideration updated occurrence data of the species in Europe, and secondly, a spatial logic conditional model based on the temperature requirements of the species and using land surface temperature data (LST model).

Results

Suitability assessment obtained with the MaxEnt model at European level accurately reflect the current distribution of the species and these results also depict moderately low values in parts of the Netherlands, Belgium, Denmark, the British islands and southern parts of Scandinavia. Winter temperature was the variable that contributed most to the performance of the model (47.3%). The results of the LST model showed that: (i) coastal areas are suitable for overwintering of eggs; (ii) large areas in the northern part of the country have a low suitability for adult survival; and (iii) the entire country is suitable for successful completion of the life-cycle if the species is introduced after the winter months. Results of the LST model revealed that temperatures in 2012 and 2014 did not limit the overwintering of eggs or survival of adults at the locations where the species was found. By contrast, for the years 2010, 2011 and 2013, overwintering of eggs at these locations is considered unlikely.

Conclusions

Results using two modelling methodologies show differences in predicted habitat suitability values. Based on the results of both models, the climatic conditions could hamper the successful overwintering of eggs of Ae. albopictus and their survival as adults in many areas of the country. However, during warm years with mild winters, many areas of the Netherlands offer climatic conditions suitable for developing populations. Regular updates of the models, using updated occurrence and climatic data, are recommended to study the areas at risk.
Occurrence of anterior uveitis in patients with spondyloarthritis treated with tumor necrosis factor inhibitors: comparing the soluble receptor to monoclonal antibodies in a large observational cohort
Authors: Khoury Gisèle , Morel Jacques , Combe Bernard , Lukas Cédric
Published: April 2020

Background

The objective of this study was to compare in real life the occurrence of anterior uveitis in patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA), treated with the soluble-receptor etanercept (ETA) or monoclonal antibodies (mAbs).

Methods

This was an observational, retrolective study. Patients with SpA who were prescribed anti-TNF agents between 2000 and 2014 were included. The risk of uveitis was interpreted qualitatively (number of subjects with at least one uveitis) and quantitatively (number of uveitis flares for each individual). Models were adjusted for propensity score of receiving preferentially mAbs or ETA.

Results

Four hundred twenty-nine patients were included (302 with SpA and 127 with PsA); 203 received a mAb and 226 ETA as a first TNF-α inhibitor. Probability of uveitis occurring during the first year of treatment was lower with ETA than with mAbs but not significantly (odds ratio 0.94 [95% confidence interval 0.35; 2.54], p = 0.90, on qualitative analysis and relative risk 0.62 [0.26; 1.46], p = 0.27, on quantitative analysis) after adjustment for the propensity score. The over-time risk of uveitis was numerically higher with ETA than with mAbs, but the differences were not statistically significant.

Conclusion

In this observational study, the risk of uveitis in patients with SpA does not appear to be greater with ETA than with mAb treatment. The occurrence of uveitis in patients receiving an anti-TNF-α agent seems linked more to the history of uveitis than the prescribed molecule.