bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between caesarean section and breastfeeding: evidence from the 2013 Turkey demographic and health survey
Authors: Paksoy Erbaydar Nüket , Erbaydar Tuğrul
Published: January 2020

Background

The mode of delivery influences breastfeeding practices. High rates of caesarean section and low breastfeeding rates are important public health concerns for all developing countries. This study aimed to determine the relationship between caesarean section and early breastfeeding practices among primiparae.

Methods

Data for primiparae with a singleton birth (N = 777) obtained from the 2013 Turkey Demographic and Health Survey were used in this retrospective cohort study. Early initiation of breastfeeding within one hour of delivery and exclusive breastfeeding during the first three days following birth were evaluated. Standardised incidence rates and standardised rate ratios of non-early initiation of breastfeeding and non-exclusive breastfeeding were calculated according to the mode of delivery.

Results

The late initiation of breastfeeding and non-exclusive breastfeeding incidence rates were 42.7 and 41.0%, respectively. The standardised incidence rate of late initiation of breastfeeding among women with vaginal delivery was 35.34%, versus 50.49% among those with caesarean delivery. The standardised rate ratios for late initiation of breastfeeding and non-exclusive breastfeeding were 1.428 (95% confidence interval (CI): 1.212–1.683) and 1.468 (95% CI: 1.236–1.762), respectively. Women who underwent caesarean section had a higher risk of late initiation of breastfeeding and non-exclusive breastfeeding during the three days following delivery, after controlling for sociodemographic and delivery-related factors.

Conclusions

This study provides useful evidence for the implementation of strategies to prevent unnecessary caesarean sections, which negatively affect not only maternal health but also neonatal health. The promotion of mother-friendly policies by healthcare institutions, implemented in a baby-friendly manner, is essential.
Key genes with prognostic values in suppression of osteosarcoma metastasis using comprehensive analysis
Authors: Li Mi , Jin Xin , Li Hao , Wu Gang , Wang Shanshan , Yang Caihong , Deng Sisi
Published: January 2020

Background

Osteosarcoma is a primary malignant tumor originating from mesenchymal tissue, with a poor distant metastasis prognosis. The molecular mechanisms of osteosarcoma metastasis are extremely complicated.

Methods

A public data series (GSE21257) was used to identify differentially expressed genes (DEGs) in osteosarcoma patients that did, or did not, develop metastases. Functional enrichment analysis, a protein-protein interaction network, and survival analysis of DEGs were performed. DEGs with a prognostic value were considered as candidate genes and their functional predictions, different expression in normal and malignant tissues, and immune infiltration were analyzed.

Results

The DEGs were mainly enriched in the immune response. Three candidate genes (ALOX5AP, CD74, and FCGR2A) were found, all of which were expressed at higher levels in lungs and lymph nodes than in matched cancer tissues and were probably expressed in the microenvironment.

Conclusions

Candidate genes can help us understand the molecular mechanisms underlying osteosarcoma metastasis and provide targets for future research.
Combination therapy with Olaratumab/doxorubicin in advanced or metastatic soft tissue sarcoma -a single-Centre experience
Authors: Striefler Jana Käthe , Brandes Franziska , Baur Alexander , Pfitzner Berit Maria , Kaul David , Rau Daniel , Dörr Anne , Schmiester Maren , Koulaxouzidis Georgios , Bullinger Lars , Märdian Sven , Flörcken Anne
Published: January 2020

Background

The antibody targeting platelet-derived growth factor receptor alpha (PDGFRA), olaratumab, was approved in 2016 for metastatic soft tissue sarcoma (STS) in combination with doxorubicin based on promising results of a phase Ib/II trial by the Food and Drug Administration (FDA). However, recently the phase III ANNOUNCE trial could not confirm the additional value of olaratumab in this context.

Methods

Here, in a retrospective analysis we share our single-centre experience with olaratumab/doxorubicin in STS by includingn = 32 patients treated with olaratumab/doxorubicin between 2016 and 2019.

Results

Median progression-free survival (PFS) in the overall cohort was 3.1 months (range 0.6–16.2). A response [complete remission (CR), partial remission (PR) or stable disease (SD)] was seen inn = 11 (34%) cases, whereasn = 21 (66%) patients showed progressive disease (PD). Inn = 9 patients surgery was performed subsequently in an individual therapeutic approach. Out ofn = 5 patients receiving additional regional hyperthermia,n = 3 achieved PR or SD.

Conclusions

This single-centre experience does also not support the promising phase Ib/II results for olaratumab/doxorubicin in STS. However, our findings do not preclude that olaratumab combination therapy could be valuable in a neoadjuvant setting. This warrants further exploration also taking into account the heterogeneous nature of STS.
Multisystem mitochondrial diseases due to mutations in mtDNA-encoded subunits of complex I
Authors: Danhelovska Tereza , Kolarova Hana , Zeman Jiri , Hansikova Hana , Vaneckova Manuela , Lambert Lukas , Kucerova-Vidrova Vendula , Berankova Kamila , Honzik Tomas , Tesarova Marketa
Published: January 2020

Background

Maternally inherited complex I deficiencies due to mutations in MT-ND genes represent a heterogeneous group of multisystem mitochondrial disorders (MD) with a unfavourable prognosis. The aim of the study was to characterize the impact of the mutations in MT-ND genes, including the novel m.13091 T > C variant, on the course of the disease, and to analyse the activities of respiratory chain complexes, the amount of protein subunits, and the mitochondrial energy-generating system (MEGS) in available muscle biopsies and cultivated fibroblasts.

Methods

The respiratory chain complex activities were measured by spectrophotometry, MEGS were analysed using radiolabelled substrates, and protein amount by SDS-PAGE or BN-PAGE in muscle or fibroblasts.

Results

In our cohort of 106 unrelated families carrying different mtDNA mutations, we found heteroplasmic mutations in the genes MT-ND1, MT-ND3, and MT-ND5, including the novel variant m.13091 T > C, in 13 patients with MD from 12 families. First symptoms developed between early childhood and adolescence and progressed to multisystem disease with a phenotype of Leigh or MELAS syndromes. MRI revealed bilateral symmetrical involvement of deep grey matter typical of Leigh syndrome in 6 children, cortical/white matter stroke-like lesions suggesting MELAS syndrome in 3 patients, and a combination of cortico-subcortical lesions and grey matter involvement in 4 patients. MEGS indicated mitochondrial disturbances in all available muscle samples, as well as a significantly decreased oxidation of [1-14C] pyruvate in fibroblasts. Spectrophotometric analyses revealed a low activity of complex I and/or complex I + III in all muscle samples except one, but the activities in fibroblasts were mostly normal. No correlation was found between complex I activities and mtDNA mutation load, but higher levels of heteroplasmy were generally found in more severely affected patients.

Conclusions

Maternally inherited complex I deficiencies were found in 11% of families with mitochondrial diseases in our region. Six patients manifested with Leigh, three with MELAS. The remaining four patients presented with an overlap between these two syndromes. MEGS, especially the oxidation of [1-14C] pyruvate in fibroblasts might serve as a sensitive indicator of functional impairment due to MT-ND mutations. Early onset of the disease and higher level of mtDNA heteroplasmy were associated with a worse prognosis.
Age-period-cohort projection of trends in blood pressure and body mass index in children and adolescents in Hong Kong
Authors: Kwok Man Ki , Wong Irene Oi Ling , Schooling C. Mary
Published: January 2020

Background

Blood pressure (BP) and body mass index (BMI) trends during childhood and adolescence are complex, making context-specific projections necessary to inform prevention and presage changes.

Objective

This study aimed to project BP and BMI in Hong Kong Chinese children and adolescents from 2015 to 2024 based on trends in BP and BMI observed from 1996/99 to 2014.

Methods

We decomposed recent trends into sex-specific contributions of age, period and cohort using age-period-cohort linear regression with Bayesian inference and autoregressive priors based on BP in children and adolescents aged 9–18 years from 1999 to 2014 and BMI in those aged 6–18 years from 1996 to 2014. We then used the resultant models to project BP and BMI from 2015 to 2024.

Results

During the study period, systolic BP decreased from 1999 to 2004/5 before gradually increasing to 2014 during childhood (for boys: from 104.6 to 101.9 and then to 103.4 mmHg) and during adolescence. Similar patterns were observed for diastolic BP. BMI generally increased from 1996 to 2009 before falling to 2014 during childhood (e.g. for boys: from 17.2 to 18.0 and then to 17.1 kg/m2). From 2015 onwards, systolic BP was projected to increase in girls, but remain stable in boys. For both sexes, diastolic BP was projected to increase, whereas BMI was projected to decrease to 2024.

Conclusions

In this economically developed Chinese setting, future trends in BP and BMI in children and adolescents are predicted to be divergent, consistent with prior discordant trends in BP and BMI.
A comparative study of mothers of infants hospitalized in an open ward neonatal intensive care unit and a combined pod and single-family room design
Authors: Feeley Nancy , Robins Stephanie , Genest Christine , Stremler Robyn , Zelkowitz Phyllis , Charbonneau Lyne
Published: January 2020

Background

The well-being of mothers of infants requiring Neonatal Intensive Care Unit (NICU) hospitalization may be affected by the architectural design of the unit. A few recent studies suggest there may be some drawbacks of single-family rooms (SFRs) for infants and their mothers, such as isolation of mothers and reduced exposure to auditory stimulation for infants.

Purpose

To compare NICU-stress, symptoms of depression, perceptions of nurse-parent support and family-centered care, sleep disturbances, breastfeeding self-efficacy and readiness for discharge in mothers of infants cared for in an open ward (OW) to those cared for in a unit that includes both pods and SFRs.

Methods

A pre-post quasi-experimental study was conducted in a Canadian level 3 unit before and after transitioning to a new unit of 6-bed pods and SFRs. OW data were collected in 2014 and pod/SFR data 1 year after the transition in 2017 to 2018. Mothers of infants hospitalized for at least 2 weeks completed questionnaires about stress, depressive symptoms, support, family-centered care, and sleep disturbances. In the week prior to discharge, they responded to breastfeeding self-efficacy and readiness for discharge questionnaires. They described their presence in the NICU at enrollment and again prior to discharge.

Results

Pod/SFR mothers reported significantly less NICU-stress compared to OW mothers. OW mothers had greater sights and sounds stress and felt more restricted in their parental role. Pod/SFR mothers reported greater respect from staff. Controlling for maternal education, pod/SFR mothers perceived their infant’s readiness for discharge to be greater than OW mothers. There were no significant differences between groups in depressive symptoms, nurse-parent support, sleep disturbances, and breastfeeding self-efficacy.

At enrollment and again in the weeks preceding discharge, pod/SFR mothers were present significantly more hours per week than OW mothers, controlling for maternal education.

Conclusions

Further study of small pods is indicated as these units may be less stressful for parents, and enhance family-centered care, as well as maternal presence, compared to OWs.
Study protocol of a randomised clinical trial testing whether metacognitive training can improve insight and clinical outcomes in schizophrenia
Authors: Lopez-Morinigo Javier-David , Ruiz-Ruano Verónica González , Martínez Adela Sánchez Escribano , Estévez María Luisa Barrigón , Mata-Iturralde Laura , Muñoz-Lorenzo Laura , Sánchez-Alonso Sergio , Artés-Rodríguez Antonio , David Anthony S. , Baca-García Enrique
Published: January 2020

Background

Although insight in schizophrenia spectrum disorders (SSD) has been associated with positive outcomes, the effect size of previous treatments on insight has been relatively small to date. The metacognitive basis of insight suggests that metacognitive training (MCT) may improve insight and clinical outcomes in SSD, although this remains to be established.

Methods

This single-center, assessor-blind, parallel-group, randomised clinical trial (RCT) aims to investigate the efficacy of MCT for improving insight (primary outcome), including clinical and cognitive insight, which will be measured by the Schedule for Assessment of Insight (Expanded version) (SAI-E) and the Beck Cognitive Scale (BCIS), respectively, in (at least)n = 126 outpatients with SSD at three points in time: i) at baseline (T0); ii) after treatment (T1) and iii) at 1-year follow-up (T2). SSD patients receiving MCT and controls attending a non-intervention support group will be compared on insight level changes and several clinical and cognitive secondary outcomes at T1 and T2, whilst adjusting for baseline data. Ecological momentary assessment (EMA) will be piloted to assess functioning in a subsample of participants.

Discussion

To the best of our knowledge, this will be the first RCT testing the effect of group MCT on multiple insight dimensions (as primary outcome) in a sample of unselected patients with SSD, including several secondary outcomes of clinical relevance, namely symptom severity, functioning, which will also be evaluated with EMA, hospitalizations and suicidal behaviour.

Trial registration

ClinicalTrials.gov:NCT04104347. Date of registration: 26/09/2019 (Retrospectively registered).
Investigating the spatial variation and risk factors of childhood anaemia in four sub-Saharan African countries
Authors: Roberts Danielle J. , Matthews Glenda , Snow Robert W. , Zewotir Temesgen , Sartorius Benn
Published: January 2020

Background

The causes of childhood anaemia are multifactorial, interrelated and complex. Such causes vary from country to country, and within a country. Thus, strategies for anaemia control should be tailored to local conditions and take into account the specific etiology and prevalence of anaemia in a given setting and sub-population. In addition, policies and programmes for anaemia control that do not account for the spatial heterogeneity of anaemia in children may result in certain sub-populations being excluded, limiting the effectiveness of the programmes. This study investigated the demographic and socio-economic determinants as well as the spatial variation of anaemia in children aged 6 to 59 months in Kenya, Malawi, Tanzania and Uganda.

Methods

The study made use of data collected from nationally representative Malaria Indicator Surveys (MIS) and Demographic and Health Surveys (DHS) conducted in all four countries between 2015 and 2017. During these surveys, all children under the age of five years old in the sampled households were tested for malaria and anaemia. A child’s anaemia status was based on the World Health Organization’s cut-off points where a child was considered anaemic if their altitude adjusted haemoglobin (Hb) level was less than 11 g/dL. The explanatory variables considered comprised of individual, household and cluster level factors, including the child’s malaria status. A multivariable hierarchical Bayesian geoadditive model was used which included a spatial effect for district of child’s residence.

Results

Prevalence of childhood anaemia ranged from 36.4% to 61.9% across the four countries. Children with a positive malaria result had a significantly higher odds of anaemia [AOR = 4.401; 95% CrI: (3.979, 4.871)]. After adjusting for a child’s malaria status and other demographic, socio-economic and environmental factors, the study revealed distinct spatial variation in childhood anaemia within and between Malawi, Uganda and Tanzania. The spatial variation appeared predominantly due to unmeasured district-specific factors that do not transcend boundaries.

Conclusions

Anaemia control measures in Malawi, Tanzania and Uganda need to account for internal spatial heterogeneity evident in these countries. Efforts in assessing the local district-specific causes of childhood anaemia within each country should be focused on.
Epidemiology of intestinal parasitic infections in preschool and school-aged Ethiopian children: a systematic review and meta-analysis
Authors: Chelkeba Legese , Mekonnen Zeleke , Alemu Yonas , Emana Daniel
Published: January 2020

Background

Numerous studies have been carried out on assessing the prevalence of intestinal parasites infections (IPIs) amongpreschool and school-age children in Ethiopia, but there is lack of study systematically gathered and analyzedinformation for policymakers. Therefore, the aim of this systematic review and meta-analysis was to provide a summary on prevalence, geographical distribution and trends of IPIs among preschool and school-age childrenin Ethiopia.

Methods

The search were carried out in Medline via PubMed, Scopus, Science Direct, Web of Science, and Google Scholar from 1996to July2019 for studies describing prevalence of IPIs among preschooland school-age children. We conducted meta-regression to understand the trends and the source of heterogeneity and pooled the prevalence using ‘metaprop’ command using STATA software version 14.

Results

Eighty-three(83) studies examining 56,786 fecal specimens were included. The prevalence of IPIs was 48%(95%CI: 42 to 53%) and showedsignificantly decreasing trends 17% (95% CI: 2.5 to 32%) for each consecutive 6 years) and was similar in males and females. The pooled prevalence in years 1997–2002, 2003–2008, 2009–2014 and > 2014 was 71% (95% CI: 57 to 86%), 42% (95% CI: 27 to 56%), 48% (95% CI: 40 to 56%) and 42% (95% CI: 34 to 49%), respectively. Poly-parasitism was observed in 16% (95% CI: 13 to 19%,) of the cases.

Conclusion

Intestinal parasite infections are highly prevalent among preschool and school-age children and well distributed across the regional states of Ethiopia. Southern and Amhara regional states carry the highest burden. We observed significant decreasing trends in prevalence of IPIs among preschool and school-ageEthiopian children over the last two decades. Therefore, this study is important to locate the geographical distribution and identified high risk areas that should be prioritized further interventions, which complement global efforts towards elimination of IPIs infections by 2020.
The design and development of a hybrid off-job crafting intervention to enhance needs satisfaction, well-being and performance: a study protocol for a randomized controlled trial
Authors: Kosenkranius Merly K. , Rink Floor A. , de Bloom Jessica , van den Heuvel Machteld
Published: January 2020

Background

Employees dealing with job demands such as high workload and permeable work-life boundaries could benefit from bottom-up well-being strategies such as off-job crafting. We have developed a hybrid off-job crafting intervention to promote off-job crafting, a proactive pursuit to adjust one’s off-job time activities to satisfy one’s psychological needs. This hybrid intervention contains both on-site (two trainings) and online elements (smartphone app) to enhance employees’ well-being and performance within different life domains.

Methods

The study is designed as a randomized controlled trial with an intervention group and a waitlist control group. The study population will be Finnish knowledge workers. The intervention program focuses on six psychological needs (detachment, relaxation, autonomy, mastery, meaning, and affiliation) proposed by the DRAMMA model. The intervention will consist of the following components: 1) an on-site off-job crafting training, 2) an individual off-job crafting plan for the four-week intervention period, 3) Everydaily smartphone app usage, and 4) a training session for reflection. The study outcomes are assessed with online questionnaires once at baseline, weekly during the intervention period and twice after the intervention (two-week and six-week follow-up). Moreover, during the second training session, participants will participate in a process evaluation to shed light on the mechanisms that can affect the effectiveness of the intervention.

Discussion

We expect that the intervention will stimulate off-job crafting behaviors, which may in turn increase well-being and performance in both non-work and work domains during and after the intervention (compared to baseline and to the control group). The intervention may provide employees with additional resources to deal with various stressors in life. Furthermore, this off-job crafting intervention could also offer performance benefits for the employers such as increased organizational citizenship behaviors among employees.

Trial registration

The Netherlands Trial Register (NTR): NL8219, December 9, 2019. Registered retrospectively. https://www.trialregister.nl/trial/8219
Comparison of quality of life between patients undergoing trans-oral endoscopic thyroid surgery and conventional open surgery
Authors: Kasemsiri Pornthep , Trakulkajornsak Srongpaun , Bamroong Piyapong , Mahawerawat Kanokkarn , Piromchai Patorn , Ratanaanekchai Teeraporn
Published: January 2020

Background

Trans-oral endoscopic thyroidectomy allows obviating scar of the neck that expects to gain quality of life (QOL). However, the benefit of the QOL from this technique has not been adequately investigated, therefore, this study compared the QOL outcomes, including cosmetic outcomes, between thyroidectomy by trans-oral endoscopy and conventional open surgery.

Methods

A study was conducted from January 30, 2017 to November 10, 2018. Thirty-two and 38 patients underwent trans-oral endoscopic thyroid surgery and conventional open surgery, respectively. Their quality of life was evaluated at 2, 6, and 12 weeks postoperatively using a thyroid surgery-specific questionnaire and a 36-item short-form questionnaire.

Results

Trans-oral endoscopic group, patients were younger and presented with smaller thyroid nodules (p < 0.05). Regarding surgical outcomes, there were no statistically significant differences between the two groups. Mean operative time was significantly longer in the trans-oral endoscopic group (p < 0.05). The quality of life parameters in the trans-oral endoscopic group was significantly better than in the conventional surgery group (p < 0.05). These parameters included reduction of physical activity, psychosocial impairment, the role of physic, and emotion at 2 weeks after surgery; swallowing impairment, psychosocial impairment, the role of physic, social function and mental health 6 weeks after surgery; tingling and feeling of vitality at 12 weeks after surgery. Cosmetic outcomes and overall satisfaction were significantly better in the trans-oral endoscopic group than in the conventional surgery group at all of our follow up times (p < 0.05).

Conclusions

The trans-oral endoscopic approach allows real scarless on the skin with better cosmetic and QOL outcomes.

Trial registration

This trial was retrospectively registered at the ClinicalTrial.gov (NCT03048539), registered on 4 March 2017.
A putative role for the aryl hydrocarbon receptor (AHR) gene in a patient with cyclical Cushing’s disease
Authors: De Sousa Sunita M. C. , Manavis Jim , Feng Jinghua , Wang Paul , Schreiber Andreas W. , Scott Hamish S. , Torpy David J.
Published: January 2020

Background

Apart from PRKAR1A mutations in a subset of cyclical Cushing’s syndrome due to primary pigmented nodular adrenocortical disease, the molecular basis of cyclical Cushing’s syndrome has not been investigated. We speculated that cyclical Cushing’s syndrome may be due to mutations in the clock genes that govern circadian rhythms, including the hypothalamic-pituitary-adrenal axis.

Case presentation

A 47-year-old man presented with mass effects from a sellar lesion. He was ultimately diagnosed with cyclical Cushing’s disease due to a giant corticotrophinoma. We performed whole exome sequencing of germline and tumour DNA, SNP array of tumour DNA and tumour immunohistochemistry in order to detect variants in candidate circadian/pituitary-associated genes. We identified a rare germline missense variant in the aryl hydrocarbon receptor (AHR) gene, which has previously been indirectly linked to pituitary tumorigenesis and clock system disruption. The AHR variant was found in a highly conserved site involved in phosphorylation. It was predicted to be damaging by multiple in silico tools and AHR tumour immunohistochemistry demonstrated loss of the normal nuclear staining pattern, suggestive of an inactivating mutation. We also found a novel, damaging germline missense variant in the retinoid X receptor gamma (RXRG) gene, multiple somatic chromosomal gains (including AHR), and a somatic mutational signature consistent with oncogenesis that may have acted synergistically with the AHR variant.

Conclusions

This is the first report of an AHR variant with predicted pathogenicity in the pituitary adenoma setting. Our preliminary data suggest that the highly conserved AHR gene may represent a link between pituitary tumorigenesis, the hypothalamic-pituitary-adrenal axis and the clock system. Further research may indicate a role for the gene in the development of cyclical Cushing’s disease.
Alisol A-24-acetate promotes glucose uptake via activation of AMPK in C2C12 myotubes
Authors: Chen Jia-xiang , Li Hai-yan , Li Tian-tian , Fu Wen-cheng , Du Xin , Liu Chun-hui , Zhang Wen
Published: January 2020

Background

Alisol A-24-acetate (AA-24-a) is one of the main active triterpenes isolated from the well-known medicinal plantAlisma orientale(Sam.) Juz., which possesses multiple biological activities, including a hypoglycemic effect. Whether AA-24-a is a hypoglycemic-active compound ofA. orientale(Sam.) Juz. is unclear. The present study aimed to clarify the effect and potential mechanism of action of AA-24-a on glucose uptake in C2C12 myotubes.

Method

Effects of AA-24-a on glucose uptake and GLUT4 translocation to the plasma membrane were evaluated. Glucose uptake was determined using a 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake assay. Cell membrane proteins were isolated and glucose transporter 4 (GLUT4) protein was detected by western blotting to examine the translocation of GLUT4 to the plasma membrane. To determine the underlying mechanism, the phosphorylation levels of proteins involved in the insulin and 5′-adenosine monophosphate-activated protein kinase (AMPK) pathways were examined using western blotting. Furthermore, specific inhibitors of key enzymes in AMPK signaling pathway were used to examine the role of these kinases in the AA-24-a-induced glucose uptake and GLUT4 translocation.

Results

We found that AA-24-a significantly promoted glucose uptake and GLUT4 translocation in C2C12 myotubes. AA-24-a increased the phosphorylation of AMPK, but had no effect on the insulin-dependent pathway involving insulin receptor substrate 1 (IRS1) and protein kinase B (PKB/AKT). In addition, the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the AKT substrate of 160 kDa (AS160), two proteins that act downstream of AMPK, was upregulated. Compound C, an AMPK inhibitor, blocked AA-24-a–induced AMPK pathway activation and reversed AA-24-a–induced glucose uptake and GLUT4 translocation to the plasma membrane, indicating that AA-24-a promotes glucose metabolism via the AMPK pathway in vitro. STO-609, a calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor, also attenuated AA-24-a–induced glucose uptake and GLUT4 translocation. Moreover, STO-609 weakened AA-24-a-induced phosphorylation of AMPK, p38 MAPK and AS160.

Conclusions

These results indicate that AA-24-a isolated fromA. orientale(Sam.) Juz. significantly enhances glucose uptake via the CaMKKβ-AMPK-p38 MAPK/AS160 pathway.
A mixed methods quality improvement study to implement nurse practitioner roles and improve care for residents in long-term care facilities
Authors: Kilpatrick Kelley , Tchouaket Éric , Jabbour Mira , Hains Sylvie
Published: January 2020

Background

To better meet long-term care (LTC) residents’ (patients in LTC) needs, nurse practitioners (NPs) were proposed as part of a quality improvement initiative. No research has been conducted in LTC in Québec Canada, where NP roles are new. We collected provider interviews, field notes and resident outcomes to identify how NPs in LTC influence care quality and inform the wider implementation of these roles in Québec. This paper reports on resident outcomes and field notes.

Methods

Research Design:This mixed methods quality improvement study included a prospective cohort study in six LTC facilities in Québec.Participants:Data were collected from September 2015–August 2016. The cohort consisted of all residents (n = 538) followed by the nurse practitioners. Nurse practitioner interventions (n = 3798) related to medications, polypharmacy, falls, restraint use, transfers to acute care and pressure ulcers were monitored.Analysis:Bivariate analyses and survival analysis of occurrence of events over time were conducted. Content analysis was used for the qualitative data.

Results

Nurse practitioners (n = 6) worked half-time in LTC with an average caseload ranging from 42 to 80 residents. Sites developed either a shared care or a consultative model. The average age of residents was 82, and two thirds were women. The most common diagnosis on admission was dementia (62%,n = 331). The number of interventions/resident (range: 2.2–16.3) depended on the care model. The average number of medications/resident decreased by 12% overall or 10% for each 30-day period over 12 months. The incidence of polypharmacy, falls, restraint use, and transfers to acute care decreased, and very few pressure ulcers were identified.

Conclusions

The implementation of NPs in LTC in Québec can improve care quality for residents. Results show that the average number of medications per day per resident, the incidence of polypharmacy, falls, restraint use, and transfers to acute care all decreased during the study, suggesting that a wider implementation of NP roles in LTC is a useful strategy to improve resident care. Although additional studies are needed, the implementation of a consultative model should be favoured as our project provides preliminary evidence of the contributions of these new roles in LTC in Québec.
Improving delivery of care in rural emergency departments: a qualitative pilot study mobilizing health professionals, decision-makers and citizens in Baie-Saint-Paul and the Magdalen Islands, Québec, Canada
Authors: Fleet Richard , Turgeon-Pelchat Catherine , Smithman Mélanie Ann , Alami Hassane , Fortin Jean-Paul , Poitras Julien , Ouellet Jean , Gravel Jocelyn , Renaud Marie-Pierre , Dupuis Gilles , Légaré France
Published: January 2020

Background

Emergency departments (EDs) in rural and remote areas face challenges in delivering accessible, high quality and efficient services. The objective of this pilot study was to test the feasibility and relevance of the selected approach and to explore challenges and solutions to improve delivery of care in selected EDs.

Methods

We conducted an exploratory multiple case study in two rural EDs in Québec, Canada. A survey filled out by the head nurse for each ED provided a descriptive statistical portrait. Semi-structured interviews were conducted with ED health professionals, decision-makers and citizens (n = 68) and analyzed inductively and thematically.

Results

The two EDs differed with regards to number of annual visits, inter-facility transfers and wait time. Stakeholders stressed the influence of context on ED challenges and solutions, related to: 1) governance and management (e.g. lack of representation, poor efficiency, ill-adapted standards); 2) health services organization (e.g. limited access to primary healthcare and long-term care, challenges with transfers); 3) resources (e.g. lack of infrastructure, limited access to specialists, difficult staff recruitment/retention); 4) and professional practice (e.g. isolation, large scope, maintaining competencies with low case volumes, need for continuing education, teamwork and protocols). There was a general agreement between stakeholder groups.

Conclusions

Our findings show the feasibility and relevance of mobilizing stakeholders to identify context-specific challenges and solutions. It confirms the importance of undertaking a larger study to improve the delivery of care in rural EDs.
Prevention strategies to identify LASA errors: building and sustaining a culture of patient safety
Authors: Lizano-Díez Irene , Figueiredo-Escribá Carlos , Piñero-López M. Ángeles , Lastra Cecilia F. , Mariño Eduardo L. , Modamio Pilar
Published: January 2020

Background

Potential look-alike, sound-alike (LASA) errors in outpatient and inpatient prescriptions have been widely described worldwide. However, most strategies of reducing drug name confusion have been only focused on the processes of prescribing and dispensing, often following local rules.

Main text

An illustrative recent example about this topic is given: the antidepressant Brintellix® (vortioxetine) (Takeda Pharmaceuticals USA, Inc.) and the antiplatelet medication Brilinta® (ticagrelor) (AstraZeneca LP). Revision of the initiatives that are currently applied to prevent potential LASA errors in different countries around the world and debate about the emerging strategies that could be implemented in short and mid-term. At present, a common policy worldwide on the authorization of unique names for innovative medicines does not exist. The implication of authorities in topdown strategies and the importance of developing an international health policy on the authorization of unique names for innovative medicines are highlighted in the following piece of opinion.

Conclusions

Building and sustaining a culture of patient safety should be considered as a global top-down strategy which involved all the elements in the system (regulatory bodies, manufacturers and suppliers). The precedent established by the FDA in prevention strategies to identify and avoid LASA errors has been extremely important and should lead to international discussion. Coordinated international efforts are urgently needed in this area for the sake of patients’ safety.
Effect of gga-miR-155 on cell proliferation, apoptosis and invasion of Marek’s disease virus (MDV) transformed cell line MSB1 by targeting RORA
Authors: Ding Ke , Yu Zu-Hua , Yu Chuan , Jia Yan-Yan , He Lei , Liao Cheng-Shui , Li Jing , Zhang Chun-Jie , Li Yin-Ju , Wu Ting-Cai , Cheng Xiang-Chao , Zhou Zi-Yu , Yu Zu-Ling
Published: January 2020

Background

Marek’s disease (MD) is caused by the oncogenic Marek’s disease virus (MDV), and is a highly contagious avian infection with a complex underlying pathology that involves lymphoproliferative neoplasm formation. MicroRNAs (miRNAs) act as oncogenes or tumor suppressors in most cancers. The gga-miR-155 is downregulated in the MDV-infected chicken tissues or lymphocyte lines, although its exact role in tumorigenesis remains unclear. The aim of this study was to analyze the effects of gga-miR-155 on the proliferation, apoptosis and invasiveness of an MDV-transformed lymphocyte line MSB1 and elucidate the underlying mechanisms.

Results

The expression level of gga-miR-155 was manipulated in MSB1 cells using specific mimics and inhibitors. While overexpression of gga-miR-155 increased proliferation, decreased the proportion of G1 phase cells relative to that in S and G2 phases, reduced apoptosis rates and increased invasiveness. However, its downregulation had the opposite effects. Furthermore, gga-miR-155 directly targeted the RORA gene and downregulated its expression in the MSB1 cells.

Conclusion

The gga-miR-155 promotes the proliferation and invasiveness of the MDV-transformed lymphocyte line MSB1 and inhibits apoptosis by targeting the RORA gene.
Diverse roles of epidermal growth factors receptors in oral and cutaneous canine melanomas
Authors: Veloso Emerson Soares , Gonçalves Ivy Nayra Nascimento , Silveira Tatiany Luiza , Oliveira Fernando Soares , Vieira Déborah Soares , Cassali Geovanni Dantas , Del Puerto Helen Lima , Ferreira Enio
Published: January 2020

Background

The epidermal growth factor receptors participate in the physiological processes such as regulation of morphogenesis, proliferation and cell migration, but when overexpressed or overactivated they may play an important role in neoplastic progression. Melanoma is the most aggressive skin neoplasm and is characterized by elevated invasion and low survival rates in both humans and dogs. In human melanomas the overexpression of EGFR, HER3 or HER4 is associated with poor prognosis. In canine melanomas the epidermal growth factor receptors expression has not been evaluated. Therefore, this study evaluated the expression of epidermal growth factor receptors by immunohistochemistry and investigated their relationship with morphological characteristics and proliferative indices in cutaneous and oral canine melanoma.

Results

In cutaneous melanoma an increased proliferative index was associated with increased cytoplasmic HER4 and reduced EGFR and HER3 protein expression. In oral melanomas, membranous HER2 protein expression correlated with occurrence of emboli, butERBB2gene amplification wasn’t observed.

Conclusion

Thus, our work evidenced the relationship between HER4 and the stimulus to cell proliferation in cutaneous melanomas, in addition to the relationship between HER2 and the occurrence of emboli in oral melanomas.
Quality of whole genome sequencing from blood versus saliva derived DNA in cardiac patients
Authors: Yao Roderick A. , Akinrinade Oyediran , Chaix Marie , Mital Seema
Published: January 2020

Background

Whole-genome sequencing (WGS) is becoming an increasingly important tool for detecting genomic variation. Blood derived DNA is the current standard for WGS for research or clinical purposes but may not always be feasible to acquire. The usability of DNA from saliva for WGS is not known. We compared the quality of WGS between blood versus saliva derived DNA.

Methods

WGS was performed in DNA from 531 blood and 502 saliva samples (including 5 paired samples) from participants enrolled in a heart disease biorepository. We compared the proportion of sequencing reads that mapped to non-human sources (microbiome), the sequencing coverage, and the yield and concordance of single nucleotide variant (SNV) and copy number variant (CNV) calls between blood and saliva genomes.

Results

Of 531 blood and 502 saliva samples, 46% saliva DNA failed quality control (QC) requirements for WGS compared to 6% QC failure for blood DNA. An average of 10.7% WGS reads in the saliva samples mapped to the human oral microbiome compared to 0.09% WGS reads in blood samples. However, these reads were readily excluded by excluding reads that did not map to the human reference genome. Sequencing coverage met or exceeded the target sequencing depth of 30x in all the blood samples and 4 of the 5 saliva samples; the fifth saliva sample had an average sequencing depth of 22.6x. Over 95% of SNVs identified in saliva were concordant with those identified in blood across the genome, within all gene coding regions, and within cardiovascular disease-related gene coding regions. Rare SNVs, defined as those with a minor allele frequency of less than 1% in the Genome Aggregation Database, had a lower concordance of 90% between blood and saliva genomes. CNVs had only 76% concordance between blood and saliva samples.

Conclusions

High quality saliva samples that meet stringent QC criteria can be used for WGS when blood-derived DNA is not available or is not suitable. Saliva DNA provides an acceptable yield of SNV calls but has a lower yield for CNV calls compared to blood DNA.
Cardiometabolic comorbidities in obstructive sleep apnea patients are related to disease severity, nocturnal hypoxemia, and decreased sleep quality
Authors: André Stephanie , Andreozzi Fabio , Van Overstraeten Chloé , Ben Youssef Sidali , Bold Ionela , Carlier Sarah , Gruwez Alexia , Bruyneel Anne-Violette , Bruyneel Marie
Published: January 2020

Background

Obstructive sleep apnea syndrome (OSA) is currently recognized as an independent risk factor for hypertension, arrhythmia, coronary heart disease, stroke, and metabolic disorders (e.g. diabetes, dyslipidemia). In clinical practice, apnea-hypopnea index (AHI) is the marker used to classify disease severity and guide treatment. However, AHI alone does not sufficiently identify OSA patients at risk for cardiometabolic comorbidities. With this in mind, the aim of this retrospective study was to determine whether some polysomnographic parameters (e.g. apnea-hypopnea duration, sleep structure, nocturnal hypoxemia) are specifically associated with cardiometabolic comorbidities in OSA.

Methods

In this retrospective study, 1717 patients suffering from moderate/severe OSA were included between 2013 and 2017. Data on demographics, comorbidities, and polysomnographic characteristics were collected and analyzed to identify factors associated with cardiometabolic complications.

Results

The medical files of 1717 patients (68% male) were reviewed. The mean AHI was 43.1 +/− 27.7 with 57.3% of patients suffering from severe OSA, and 52% from at least one cardiovascular comorbidity (CVCo). Diabetes affected 22% of the patients and 27% exhibited dyslipidemia. Patients affected by CVCos were older, and more often women and non-smokers. These patients also had worse sleep quality, and a more marked intermittent/global nocturnal hypoxemia. With regard to diabetes, diabetics were older, more often non-smoker, non-drinker women, and were more obese. These patients also exhibited more severe OSA, especially in non-REM (NREM) sleep, worse sleep quality, and a more marked intermittent/global nocturnal hypoxemia. Dyslipidemia was more frequent in the absence of alcohol consumption, and was associated with OSA severity, decreased sleep quality, and longer AH in REM sleep.

Conclusions

This study identifies demographic and polysomnographic factors associated with cardiometabolic comorbidities. Patients (especially women) suffering from more severe OSA, longer sleep apneas and hypopneas, worse sleep quality, and marked intermittent/global nocturnal hypoxemia are more likely to develop cardiometabolic comorbidities. This should stimulate clinicians to obtain adequate treatment in this population.
The IL-15 / sIL-15Rα complex modulates immunity without effect on asthma features in mouse
Authors: Moui Antoine , Klein Martin , Hassoun Dorian , Dijoux Eléonore , Cheminant Marie-Aude , Magnan Antoine , Bouchaud Grégory
Published: January 2020

Background

Interleukin 15 (IL-15) is a growth and modulating factor for B, T lymphocytes and natural killer cells (NK). Its action on innate and adaptive immunity is modulated by its alpha chain receptor (IL-15Rα). The IL-15/sIL-15Rα complex (IL-15Cx) increases the bioavailability and activity of the cytokine in vivo. IL-15Cx has been used in diseases to dampen IL-15 inflammation by the use of soluble IL-15Ralpha specificity. Here, we aim to evaluate the interest of IL-15Cx in a mouse model of asthma.

Methods

Using a mouse model of asthma consisting in percutaneous sensitization and intranasal challenge with total house dust mite extract, we evaluated the effect of IL-15Cx injected intraperitoneally four times after a first nasal challenge. Respiratory function was assessed by the technique of forced oscillations (Flexivent®). The effect on bronchial remodeling was evaluated by lung histology. The inflammatory status was analyzed by flow cytometry.

Results

We observed that the IL-15Cx modulates lung and systemic inflammation by increasing NK cells, CD8+ memory T cells and regulatory cells. However, IL-15Cx displays no effect on bronchial hyperreactivity, bronchial remodeling nor cellular bronchial infiltrate, but limits the secretion of bronchial mucus and modulates only inflammatory response in a HDM-allergic asthma murine model.

Conclusions

IL-15Cx has a limited effect on immune response in asthma and has no effect on lung function in mice. Thus, it limits its therapeutic potential but might suggest a combinatory potential with other therapeutics.
Monitoring and external control of pH in microfluidic droplets during microbial culturing
Authors: Tovar Miguel , Mahler Lisa , Buchheim Stefanie , Roth Martin , Rosenbaum Miriam A.
Published: January 2020

Background

Cell-based experimentation in microfluidic droplets is becoming increasingly popular among biotechnologists and microbiologists, since inherent characteristics of droplets allow high throughput at low cost and space investment. The range of applications for droplet assays is expanding from single cell analysis toward complex cell–cell incubation and interaction studies. As a result of cellular metabolism in these setups, relevant physicochemical alterations frequently occur before functional assays are conducted. However, to use droplets as truly miniaturized bioreactors, parameters like pH and oxygen availability should be controlled similar to large-scale fermentation to ensure reliable research.

Results

Here, we introduce a comprehensive strategy to monitor and control pH for large droplet populations during long-term incubation. We show the correlation of fluorescence intensity of 6-carboxyfluorescein and pH in single droplets and entire droplet populations. By taking advantage of inter-droplet transport of pH-mediating molecules, the average pH value of several million droplets is simultaneously adjusted in an a priori defined direction. To demonstrate the need of pH control in practice, we compared the fermentation profiles of two E. coli strains, a K12-strain and a B-strain, in unbuffered medium with 5 g/L glucose for standard 1 L bioreactors and 180 pL droplets. In both fermentation formats, the commonly used B-strain E. coli BL21 is able to consume glucose until depletion and prevent a pH drop, while the growth of the K12-strain E. coli MG1655 is soon inhibited by a low pH caused by its own high acetate production. By regulating the pH during fermentation in droplets with our suggested strategy, we were able to prevent the growth arrest of E. coli MG1655 and obtained an equally high biomass yield as with E. coli BL21.

Conclusion

We demonstrated a comparable success of pH monitoring and regulation for fermentations in 1 L scale and 180 pL scale for two E. coli strains. This strategy has the potential to improve cell-based experiments for various microbial systems in microfluidic droplets and opens the possibility for new functional assay designs.