bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental validation and computational modeling of anti-influenza effects of quercetin-3-O-α-L-rhamnopyranoside from indigenous south African medicinal plant Rapanea melanophloeos
Authors: Mehrbod Parvaneh , Ebrahimi Samad Nejad , Fotouhi Fatemeh , Eskandari Fatemeh , Eloff Jacobus N. , McGaw Lyndy J. , Fasina Folorunso O.
Published: December 2019

Background

Influenza A virus (IAV) is still a major health threat. The clinical manifestations of this infection are related to immune dysregulation, which causes morbidity and mortality. The usage of traditional medication with immunomodulatory properties against influenza infection has been increased recently. Our previous study showed antiviral activity of quercetin-3-O-α-L-rhamnopyranoside (Q3R) isolated from Rapanea melanophloeos (RM) (L.) Mez (family Myrsinaceae) against H1N1 (A/PR/8/34) infection. This study aimed to confirm the wider range of immunomodulatory effect of Q3R on selective pro- and anti-inflammatory cytokines against IAV in vitro, to evaluate the effect of Q3R on apoptosis pathway in combination with H1N1, also to assess the physical interaction of Q3R with virus glycoproteins and RhoA protein using computational docking.

Methods

MDCK cells were exposed to Q3R and 100CCID50/100 μl of H1N1 in combined treatments (co-, pre- and post-penetration treatments). The treatments were tested for the cytokines evaluation at RNA and protein levels by qPCR and ELISA, respectively. In another set of treatment, apoptosis was examined by detecting RhoA GTPase protein and caspase-3 activity. Molecular docking was used as a tool for evaluation of the potential anti-influenza activity of Q3R.

Results

The expressions of cytokines in both genome and protein levels were significantly affected by Q3R treatment. It was shown that Q3R was much more effective against influenza when it was applied in co-penetration treatment. Q3R in combination with H1N1 increased caspase-3 activity while decreasing RhoA activation. The molecular docking results showed strong binding ability of Q3R with M2 transmembrane, Neuraminidase of 2009 pandemic H1N1, N1 and H1 of PR/8/1934 and Human RhoA proteins, with docking energy of − 10.81, − 10.47, − 9.52, − 9.24 and − 8.78 Kcal/mol, respectively.

Conclusions

Quercetin-3-O-α-L-rhamnopyranoside from RM was significantly effective against influenza infection by immunomodulatory properties, affecting the apoptosis pathway and binding ability to viral receptors M2 transmembrane and Neuraminidase of 2009 pandemic H1N1 and human RhoA cellular protein. Further research will focus on detecting the detailed specific mechanism of Q3R in virus-host interactions.
Operating room first case start times: a metric to assess systems-based practice milestones?
Authors: Hoffman Christopher Ryan , Horrow Jay , Ranganna Shreyas , Green Michael Stuart
Published: December 2019

Background

Resident competence in peri-operative care is a reflection on education and cost-efficiency. Inspecting pre-existing operating room metrics for performance outliers may be a potential solution for assessing competence. Statistical correlation of problematic benchmarks may reveal future opportunities for educational intervention.

Methods

Case-log database review yielded 3071 surgical cases involving residents over the course of 5 years. Surgery anticipated and actual start times were evaluated for delays and residents were assessed using the days of resident training performed at the time of each corresponding case. Other variables recorded included day of week, attending anesthesiologist name, attending surgeon name, patient age, sex, American Society of Anesthesiologists physical status classification (ASA PS), and in-patient versus day surgery status. Mixed-effect, multi-variable, linear regression determined independent determinants of delay time.

Results

The analysis identified day of the week (F = 25.65, P < 0.0001), days of training (F = 8.39, P = 0.0038), attending surgeon (F = 2.67, P < 0.0001), and anesthesiology resident (F = 1.67, P = 0.0012) as independent predictors of delay time for first-start cases, with an overall regression model F = 3.09, r2 = 0.186, and P < 0.0001.

Conclusions

The day of the week and attending surgeon demonstrated significant impact of case delay compared to resident days trained. If a learning curve for first-case start punctuality exists for anesthesiology residents, it is subtle and irrelevant to operating room efficiency. The regression model accounted for only 19% of the variability in the outcome of delay time, indicating a multitude of additional unidentified factors contributing to operating room efficiency.
Correction to: Community participation and private sector engagement are fundamental to achieving universal health coverage and health security in Africa: reflections from the second Africa health forum
Authors: Olu Olushayo , Drameh-Avognon Pamela , Asamoah-Odei Emil , Kasolo Francis , Valdez Tomas , Kabaniha Grace , Karamagi Humphrey , Good Suvajee , O’Malley Helena , Yoti Zabulon , Razakazoa Nirina , Minkoulou Etienne , Dangou Jean-Marie , Mbassi Symplice Mbola , Castellon Mariano Salazar , Cabore Joseph , Moeti Matshidiso
Published: December 2019

Following publication of the original article [1], the authors reported the following author name error is the article:
Correction to: A functional polymorphism in the promoter of miR-17-92 cluster is associated with decreased risk of ischemic stroke
Authors: Huang Huatuo , Wei Guijiang , Wang Chunfang , Lu Yulan , Liu Chunhong , Wang Rong , Shi Xiang , Yang Jun , Wei Yesheng
Published: December 2019

Following publication of the original article [1], it was reported that during the production process, Fig. 3b was omitted from the final article.
DNA methylation is associated with lung function in never smokers
Authors:   BIOS Consortium, de Vries Maaike , Nedeljkovic Ivana , van der Plaat Diana A. , Zhernakova Alexandra , Lahousse Lies , Brusselle Guy G. , Amin Najaf , van Duijn Cornelia M. , Vonk Judith M. , Boezen H. Marike
Published: December 2019

Background

Active smoking is the main risk factor for COPD. Here, epigenetic mechanisms may play a role, since cigarette smoking is associated with differential DNA methylation in whole blood. So far, it is unclear whether epigenetics also play a role in subjects with COPD who never smoked. Therefore, we aimed to identify differential DNA methylation associated with lung function in never smokers.

Methods

We determined epigenome-wide DNA methylation levels of 396,243 CpG-sites (Illumina 450 K) in blood of never smokers in four independent cohorts, LifeLines COPD&C (N = 903), LifeLines DEEP (N = 166), Rotterdam Study (RS)-III (N = 150) and RS-BIOS (N = 206). We meta-analyzed the cohort-specific methylation results to identify differentially methylated CpG-sites with FEV1/FVC. Expression Quantitative Trait Methylation (eQTM) analysis was performed in the Biobank-based Integrative Omics Studies (BIOS).

Results

A total of 36 CpG-sites were associated with FEV1/FVC in never smokers at p-value< 0.0001, but the meta-analysis did not reveal any epigenome-wide significant CpG-sites. Of interest, 35 of these 36 CpG-sites have not been associated with lung function before in studies including subjects irrespective of smoking history. Among the top hits were cg10012512, cg02885771, annotated to the gene LTV1 Ribosome Biogenesis factor (LTV1), and cg25105536, annotated to Kelch Like Family Member 32 (KLHL32). Moreover, a total of 11 eQTMS were identified.

Conclusions

With the identification of 35 CpG-sites that are unique for never smokers, our study shows that DNA methylation is also associated with FEV1/FVC in subjects that never smoked and therefore not merely related to smoking.
Relationship between diffusion capacity and small airway abnormality in COPDGene
Authors: Criner Rachel N. , Hatt Charles R. , Galbán Craig J. , Kazerooni Ella A. , Lynch David A. , McCormack Meredith C. , Casaburi Richard , MacIntyre Neil R. , Make Barry J. , Martinez Fernando J. , Labaki Wassim W. , Curtis Jeffrey L. , Han Mei Lan K.
Published: December 2019

Impaired single breath carbon monoxide diffusing capacity (DLCO) is associated with emphysema. Small airways disease (SAD) may be a precursor lesion to emphysema, but the relationship between SAD and DLCO is undescribed. We hypothesized that in mild COPD, functional SAD (fSAD) defined by computed tomography (CT) and Parametric Response Mapping methodology would correlate with impaired DLCO. Using data from ever-smokers in the COPDGene cohort, we established that fSAD correlated significantly with lower DLCO among both non-obstructed and GOLD 1–2 subjects. The relationship between DLCO with CT-defined emphysema was present in all GOLD stages, but most prominent in severe disease.

Trial registration

NCT00608764. Registry: COPDGene. Registered 06 February 2008, retrospectively registered.
The m6A eraser FTO facilitates proliferation and migration of human cervical cancer cells
Authors: Zou Dongling , Dong Lei , Li Chenying , Yin Zhe , Rao Shuan , Zhou Qi
Published: December 2019

Background

Since FTO was recognized as the first m6A demethylase, the understanding of its biological function has been widely expanded. However, the role of FTO in cervical cancer tumorigenesis remains unclear.

Methods

In this study, we first analyzed the expression of FTO in two independent human cancer datasets and evaluated the correlation between FTO level and cervical cancer progression. Using small hairpin RNA technology, we explored the function of FTO in cervical cancer cell line Hela and SiHa cells, respectively. We then determined the FTO targets by performing transcriptional profile with FTO deficient and competent Hela cells, and finally validated these targets with ribosome profiling and functional rescue experiments.

Results

Our data suggested that FTO was frequently overexpressed in human cervical cancer tissues and highly correlated with cervical cancer progression. FTO serves as an oncogenic regulator for cervical cancer cells’ proliferation and migration which is vastly depended on its demethylase activity. Mechanistically, FTO interacts with transcripts of E2F1 and Myc, inhibition of FTO significantly impairs the translation efficiency of E2F1 and Myc, however, either overexpress E2F1 or Myc sufficiently compensates the FTO deficiency which decreases cell proliferation and migration.

Conclusions

Our study indicates that FTO plays important oncogenic role in regulating cervical cancer cells’ proliferation and migration via controlling m6A modification of E2F1 and Myc transcripts. FTO represents a potential drug candidate for cervical cancer therapy.
Effect of vitamin D fortified foods on bone markers and muscle strength in women of Pakistani and Danish origin living in Denmark: a randomised controlled trial
Authors: Grønborg Ida M. , Tetens Inge , Andersen Elisabeth Wreford , Kristensen Michael , Larsen Rikke E. K. , Tran Thanh L. L. , Andersen Rikke
Published: December 2019

Background

Deficient and insufficient vitamin D status (defined as serum 25(OH)D < 30 nmol/L and > 50 nmol/L) is prevalent worldwide and associated with decreased muscle strength and poor bone health. We aimed to investigate the effect of vitamin D fortification on bone markers and muscle strength among younger adult women at risk of vitamin D deficiency.

Methods

A 12-week randomised double-blinded placebo-controlled winter intervention trial, providing 30 μg vitamin D3/day through fortified yoghurt, cheese, eggs and crisp-bread or similar placebo products. Participants were 143 women of Danish and Pakistani origin 18–50 years of age, living in Denmark, randomised into four groups stratified by ethnicity. Serum 25-hydroxyvitamin D (25(OH)D) by LC-MS/MS and the secondary endpoints: four specific bone markers (osteocalcin (OC), Bone specific Alkaline Phosphatase (BALP), Procollagen type 1 amino-terminal propeptide (P1NP), C-terminal crosslinked telopeptide of type 1 collagen (CTX)) and three muscle strength measures (handgrip, knee extension strength, chair-standing), were assessed using one-way ANOVA, Tukey HSD and subsequent linear ANCOVA models, adjusted for relevant covariates.

Results

Significantly increased serum 25(OH)D concentration from 53.3 (17) to 77.8 (14) nmol/L and from 44.5 (21) to 54.7 (18) nmol/L among Danish and Pakistani women in the fortified groups, respectively (P <  0.05). The bone turnover markers OC, BALP, P1NP and CTX did not change significantly. Muscle strength by handgrip, knee extension and chair-standing test did not change significantly following the intervention.

Conclusions

Consumption of vitamin D fortified foods for 12 weeks did not result in significant changes of the bone turnover markers OC, BALP, P1NP and CTX. Muscle strength measured as hand grip strength, knee extension strength and chair-standing did not change significantly following the intervention.
Do dietary intakes influence the rate of decline in anti-Mullerian hormone among eumenorrheic women? A population-based prospective investigation
Authors: Moslehi Nazanin , Mirmiran Parvin , Azizi Fereidoun , Tehrani Fahimeh Ramezani
Published: December 2019

Background

Dietary intakes are suggested to affect age at menopause but associations between dietary factors and ovarian reserve reduction have not yet been investigated. We aimed to examine dietary intakes in relation to the rate of decline in anti-Mullerian hormone (AMH), an indicator of ovarian reserve, in a generally healthy cohort of women.

Methods

This prospective investigation was conducted among 227 eumenorrheic women, aged 20–50 years, from the Tehran Lipid and Glucose study, who were followed over a mean of 16 years. AMH was measured twice, at baseline and the 5th follow-up examination cycle, and yearly rate of decline in AMH was calculated. Rapid decline in AMH was defined as the annual percent change AMH > 5.9%/year based on tertile 3 of the variable. Average usual dietary intakes were estimated using the food frequency questionnaires administered at the second, third, and the fourth follow-up examinations. After adjusting for potential covariates, the association between dietary factors and both risk of rapid decline in AMH and also annual percent decline of AMH (as a continuous variable) were examined using logistic regression and the Spearman correlation, respectively.

Results

The baseline age of the participants and the median rate of decline in AMH were 37.2 years and was 5.7% yearly, respectively. The odds of rapid decline in AMH was reduced by 47% for dairy products (95% CIs = 0.36, 0.79;p = 0.002), 38% for milk (95% CIs = 0.41, 0.93;p = 0.020), and 36% for fermented dairy (95% CIs = 0.45, 0.93,p = 0.018) per one standard deviation (SD) increase in their dietary intakes. The odds of rapid decline in AMH was significantly reduced with higher intakes of fat, carbohydrate, protein, and calcium intakes from dairy sources, lactose and galactose. Annual rate of AMH decline was inversely correlated with dairy products, milk, fermented dairy, fruits, dairy carbohydrate, dairy fat, dairy protein, total calcium and dairy calcium, lactose and galactose, and positively correlated with organ meats.

Conclusion

Dairy foods consumption may reduce the rate of AMH decline in regularly menstruating women. Life style modification in terms of dietary advice may be considered as a preventive strategy for reduction in the rate of ovarian reserve loss.
Horizontal equity in access to public GP services by socioeconomic group: potential bias due to a compartmentalised approach
Authors: Negrín M. A. , Pinilla J. , Abásolo I.
Published: December 2019

Background

Horizontal equity in access to public general practitioner (GP) services by socioeconomic group has been addressed econometrically by testing the statement “equal probability of using public GP services for equal health care needs, regardless of socioeconomic status”. Based on survey data, the conventional approach has been to estimate binomial econometric models in which when the respondent reports having visited a public GP, it counts as 1, otherwise it counts as 0. This is what we call a compartmentalised approach. Those respondents who did not visit a public GP but visited instead another doctor (specialist or private GP) would count as 0 (despite having used instead other modes of health care), thus conclusions of the compartmentalised approach might be biased. In such cases, a multinomial econometric model -that we called comprehensive approach- would be more appropriate to analyse horizontal equity in access to public GP services. The objective of this paper is to test for this potential bias by comparing a compartmentalised and a comprehensive approach, when analysing horizontal equity in access to public GP.

Methods

Using data from the 2016/17 Spanish National Health Survey, we estimate the probability of visiting a public GP as determined by socioeconomic status, health care need and demographic characteristics. We use binomial and multinomial logit and probit models in order to highlight the potential differences in the conclusions regarding socioeconomic inequities in access to public GP services. Socioeconomic status is proxied by education level, social class and employment situation.

Results

Our results show that conclusions are sensitive to the approach selected. Particularly, the horizontal inequity favouring individuals with lower education that resulted from the compartmentalised approach disappears under a comprehensive approach and only a social class effect remains.

Conclusion

An analysis of horizontal equity in access to a particular health care service (like public GP services) undertaken following a compartmentalised approach should be compared with a comprehensive approach in order to test that there is no bias as a consequence of considering as zeros the utilisation of other types of health care.
Glove single-port laparoscopy-assisted transanal total mesorectal excision for low rectal cancer: a preliminary report
Authors: Li Wanglin , Dong Boye , Peng Baifu , Lu Jiabao , Wu Zixin , Li Guanwei , Cao Jie
Published: December 2019

Purpose

Glove single-port laparoscopy-assisted transanal total mesorectal excision (TaTME) has been successfully carried out in our medical center. The purpose of this study is to evaluate the feasibility of this emerging operation.

Methods

This technique was performed by self-made glove single-port laparoscopic platform to radically resect low rectal cancer. Short-term postoperative results, including complications, length of hospital stay, and follow-up results were collected and analyzed statistically.

Results

There are five consecutive patients (three males, two females) who underwent this surgery and included in this study. The mean distance from the tumor to the anal verge was 4.8 cm (range 4.0–6.0). The surgery was completed in all cases, and the rectal tumor was removed successfully without conversion; circumferential margins of all the excised specimens were negative. The mean time of operation was 338.00 min (range 280–400). The average number of lymph node dissection was 12.20. The average postoperative hospital stay was 8.60 days. During the follow-up (14.80 ± 1.92 months), all preventive ileostomies were successfully closed in about 3 months after the surgery, all patients had satisfactory anal function, and no tumor recurrence was found.

Conclusion

Glove single-port laparoscopy-assisted TaTME has a significant effect in specific patients with low rectal cancer, with rapid recovery and high safety. Prospective randomized studies involving more case counts and long-term follow-up results, especially oncologic outcomes, are needed to validate this technique.
Role of the intestinal microbiome in colorectal cancer surgery outcomes
Authors: Lauka Lelde , Reitano Elisa , Carra Maria Clotilde , Gaiani Federica , Gavriilidis Paschalis , Brunetti Francesco , de’Angelis Gian Luigi , Sobhani Iradj , de’Angelis Nicola
Published: December 2019

Objectives

Growing evidence supports the role of the intestinal microbiome in the carcinogenesis of colorectal cancers, but its impact on colorectal cancer surgery outcomes is not clearly defined. This systematic review aimed to analyze the association between intestinal microbiome composition and postoperative complication and survival following colorectal cancer surgery.

Methods

A systematic review was conducted according to the 2009 PRISMA guidelines. Two independent reviewers searched the literature in a systematic manner through online databases, including Medline, Scopus, Embase, Cochrane Oral Health Group Specialized Register, ProQuest Dissertations and Theses Database, and Google Scholar. Human studies investigating the association between the intestinal microbiome and the short-term (anastomotic leakage, surgical site infection, postoperative ileus) and long-term outcomes (cancer-specific mortality, overall and disease-free survival) of colorectal cancer surgery were selected. Patients with any stage of colorectal cancer were included. The Newcastle-Ottawa scale for case-control and cohort studies was used for the quality assessment of the selected articles.

Results

Overall, 8 studies (7 cohort studies and 1 case-control) published between 2014 and 2018 were included. Only one study focused on short-term surgical outcomes, showing that anastomotic leakage is associated with low microbial diversity and abundance of Lachnospiraceae and Bacteroidaceae families in the non-cancerous resection lines of the stapled anastomoses of colorectal cancer patients. The other 7 studies focused on long-term oncological outcomes, including survival and cancer recurrence. The majority of the studies (5/8) found that a higher level of Fusobacterium nucleatum adherent to the tumor tissue is associated with worse oncological outcomes, in particular, increased cancer-specific mortality, decreased median and overall survival, disease-free and cancer-specific survival rates. Also a high abundance of Bacteroides fragilis was found to be linked to worse outcomes, whereas the relative abundance of the Prevotella-co-abundance group (CAG), the Bacteroides CAG, and the pathogen CAG as well as Faecalibacterium prausnitzii appeared to be associated with better survival.

Conclusions

Based on the limited available evidence, microbiome composition may be associated with colorectal cancer surgery outcomes. Further studies are needed to elucidate the role of the intestinal microbiome as a prognostic factor in colorectal cancer surgery and its possible clinical implications.
Workforce requirements for comprehensive ischaemic stroke care in a developing country: the case of Saudi Arabia
Authors: Al-Senani Fahmi , Salawati Mohammad , AlJohani Mohammed , Cuche Matthieu , Seguel Ravest Valeska , Eggington Simon
Published: December 2019

Background

Ischaemic stroke care requires a co-ordinated multi-disciplinary approach to optimise patient outcomes. Current care provision in Saudi Arabia is below international recommendations, and with increasing patient numbers, variable access to new therapies, and sub-optimal co-ordination of staff, the Kingdom’s Ministry of Health has prioritised strategies to develop stroke care. Our objective was to use local epidemiological data to predict stroke incidence and to combine this with international staffing recommendations to estimate future staff requirements and their costs over a 10-year period.

Methods

We researched existing stroke services and staff availability within Saudi Arabia to establish current provision, undertook epidemiological modelling to predict stroke incidence, and used international staffing recommendations for acute and rehabilitation services to develop a care pathway to provide state-of-the-art stroke services. This information was used to determine the additional staff requirements, and their costs, across the Kingdom.

Results

Our research concluded that current staff numbers and services are inadequate to cope with the projected increase in the number of stroke cases. In order to provide acute and rehabilitation services which use the latest technologies, re-organisation of existing staff and services would be required, together with significant investment in new staff across several disciplines. An estimated additional 43.8 full-time equivalent stroke neurologists would be required, plus 53.5 full-time equivalent interventional neuroradiologists in addition to expansion of occupational therapy and psychology services. The total cost of additional staff over 10 years was estimated to be 862 390 778 Saudi Riyals ($229 970 874).

Conclusions

Providing high-quality care for ischaemic stroke patients would involve significant investment in new staff in Saudi Arabia. Further research is required on the applicability of international staffing ratios to countries where there is a significant workforce gap. Nevertheless, this analysis provides a framework to inform stroke care planning and can be adapted to other regions or countries.
Mechanical ventilation in patients with acute ischaemic stroke: from pathophysiology to clinical practice
Authors: Robba Chiara , Bonatti Giulia , Battaglini Denise , Rocco Patricia R. M. , Pelosi Paolo
Published: December 2019

Most patients with ischaemic stroke are managed on the ward or in specialty stroke units, but a significant number requires higher-acuity care and, consequently, admission to the intensive care unit. Mechanical ventilation is frequently performed in these patients due to swallowing dysfunction and airway or respiratory system compromise. Experimental studies have focused on stroke-induced immunosuppression and brain-lung crosstalk, leading to increased pulmonary damage and inflammation, as well as reduced alveolar macrophage phagocytic capability, which may increase the risk of infection. Pulmonary complications, such as respiratory failure, pneumonia, pleural effusions, acute respiratory distress syndrome, lung oedema, and pulmonary embolism from venous thromboembolism, are common and found to be among the major causes of death in this group of patients. Furthermore, over the past two decades, tracheostomy use has increased among stroke patients, who can have unique indications for this procedure—depending on the location and type of stroke—when compared to the general population. However, the optimal mechanical ventilator strategy remains unclear in this population. Although a high tidal volume (VT) strategy has been used for many years, the latest evidence suggests that a protective ventilatory strategy (VT = 6–8 mL/kg predicted body weight, positive end-expiratory pressure and rescue recruitment manoeuvres) may also have a role in brain-damaged patients, including those with stroke. The aim of this narrative review is to explore the pathophysiology of brain-lung interactions after acute ischaemic stroke and the management of mechanical ventilation in these patients.
CRISPR-Cas13d mediates robust RNA virus interference in plants
Authors: Mahas Ahmed , Aman Rashid , Mahfouz Magdy
Published: December 2019

Background

CRISPR-Cas systems endow bacterial and archaeal species with adaptive immunity mechanisms to fend off invading phages and foreign genetic elements. CRISPR-Cas9 has been harnessed to confer virus interference against DNA viruses in eukaryotes, including plants. In addition, CRISPR-Cas13 systems have been used to target RNA viruses and the transcriptome in mammalian and plant cells. Recently, CRISPR-Cas13a has been shown to confer modest interference against RNA viruses. Here, we characterized a set of different Cas13 variants to identify those with the most efficient, robust, and specific interference activities against RNA viruses in planta using Nicotiana benthamiana.

Results

Our data show that LwaCas13a, PspCas13b, and CasRx variants mediate high interference activities against RNA viruses in transient assays. Moreover, CasRx mediated robust interference in both transient and stable overexpression assays when compared to the other variants tested. CasRx targets either one virus alone or two RNA viruses simultaneously, with robust interference efficiencies. In addition, CasRx exhibits strong specificity against the target virus and does not exhibit collateral activity in planta.

Conclusions

Our data establish CasRx as the most robust Cas13 variant for RNA virus interference applications in planta and demonstrate its suitability for studying key questions relating to virus biology.
Physical activity promotion in daily exercise therapy: the perspectives of exercise therapists in German rehabilitation settings
Authors: Geidl Wolfgang , Wais Judith , Fangmann Cheyenne , Demisse Ewnet , Pfeifer Klaus , Sudeck Gorden
Published: December 2019

Background

This study aims to explore exercise therapists’ perspectives on the topic of physical activity promotion (PAP) with a focus on identifying (i) the intervention content and methodological approaches used for promoting physical activity (PA) in daily practice and (ii) the barriers and facilitators that affect PAP.

Methods

This qualitative study comprised the heads of exercise therapy departments (n = 58; 41% women; mean age = 45 years) from different rehabilitation clinics in Germany. Each participant took part in a semi-structured focus-group discussion on PAP in exercise therapy. The findings of the focus groups were processed and interpreted using a conventional qualitative content analysis.

Results

The exercise therapists demonstrated detailed didactic–methodological strategies and action orientations for PAP. The identified core topics of the content and methods of PAP were (1) conceptualization, (2) exercise and PA for enjoyment and pleasure, (3) education with practice–theory combinations, (4) media and materials for self-directed training, and (5) strategies to enhance personal responsibility and independence. The core topics for the associated barriers and facilitators were (1) structural conditions, (2) the role of exercise therapists, (3) the interdisciplinary rehabilitation team, (4) rehabilitant experiences and expectations, and (5) aftercare services.

Conclusion

The topic of PAP is addressed with a high level of variability; exercise therapists involved in this study identify various methods and content for the promotion of PA within their individual practices. However, they display a limited awareness of existing evidence- and theory-based concepts for the promotion of PA as well as underlying theories of behavioural change. This variability may be due to the lack of a defined common framework for promoting PA, insufficient emphasis being placed on PA promotion in the current curricula and training, or extensive conceptual differences within German exercise therapy departments (e.g. different weighting of PAP).
RETRACTED ARTICLE: Dissecting the role of novel EZH2 inhibitors in primary glioblastoma cell cultures: effects on proliferation, epithelial-mesenchymal transition, migration, and on the pro-inflammatory phenotype
Authors: Stazi Giulia , Taglieri Ludovica , Nicolai Alice , Romanelli Annalisa , Fioravanti Rossella , Morrone Stefania , Sabatino Manuela , Ragno Rino , Taurone Samanta , Nebbioso Marcella , Carletti Raffaella , Artico Marco , Valente Sergio , Scarpa Susanna , Mai Antonello
Published: December 2019

Background

Glioblastoma (GBM) is the most lethal and aggressive malignant primary brain tumor in adults. After surgical resection of the tumor, the patient typically should be subjected to chemotherapy (temozolomide, TMZ) and concomitant radiotherapy. Since the TMZ treatment does not lead to complete remission and often develops resistance, the identification of efficacious therapeutics is strongly to pursue. Among the epigenetic players, the H3K27 methyltransferase (MT) EZH2 (enhancer of zeste homologue 2) has been found overexpressed or mutated in several human cancers including gliomas, and its overexpression is associated with poor outcome in GBM. Two EZH2 inhibitors (EZH2i), UNC1999 and GSK343, suppressed GBM growth in vitro and in vivo indicating that EZH2i can be potential drugs against GBM.

Results

Two new EZH2i, MC4040 and MC4041, were designed, prepared, and tested by us to determine their effects in primary GBM cell cultures. MC4040 and MC4041 displayed single-digit micromolar inhibition of EZH2, 10-fold less potency against EZH1, and no activity towards other MTs. In primary GBM cells as well as in U-87 GBM cells, the two compounds reduced H3K27me3 levels, and dose- and time-dependently impaired GBM cell viability without inducing apoptosis and arresting the cell cycle in the G0/G1 phase, with increased p21 and p27 levels. In combination with TMZ, MC4040 and MC4041 displayed stronger, but not additive, effects on cell viability. The potent clinical candidate as EZH2i tazemetostat, alone or in combination with TMZ, exhibited a similar potency of inhibition of GBM cell growth when compared to MC4040 and MC4041. At the molecular level, MC4040 and MC4041 reduced the VEGFR1/VEGF expression, reversed the epithelial-mesenchymal transition (EMT), and hampered cell migration and invasion attenuating the cancer malignant phenotype. Treatment of GBM cells with MC4040 and MC4041 also impaired the GBM pro-inflammatory phenotype, with a significant decrease of TGF-β, TNF-α, and IL-6, joined to an increase of the anti-inflammatory cytokine IL-10.

Conclusions

The two novel EZH2i MC4040 and MC4041 impaired primary GBM cell viability, showing even stronger effects in combination with TMZ. They also weakened the aggressive malignant phenotype by reducing angiogenesis, EMT, cell migration/invasion and inflammation, thus they may be considered potential candidates against GBM also for combination therapies.
Age-related transcriptome changes in Sox2+ supporting cells in the mouse cochlea
Authors: Cheng Cheng , Wang Yunfeng , Guo Luo , Lu Xiaoling , Zhu Weijie , Muhammad Waqas , Zhang Liyan , Lu Ling , Gao Junyan , Tang Mingliang , Chen Fangyi , Gao Xia , Li Huawei , Chai Renjie
Published: December 2019

Background

Inner ear supporting cells (SCs) in the neonatal mouse cochlea are a potential source for hair cell (HC) regeneration, but several studies have shown that the regeneration ability of SCs decreases dramatically as mice age and that lost HCs cannot be regenerated in adult mice. To better understand how SCs might be better used to regenerate HCs, it is important to understand how the gene expression profile changes in SCs at different ages.

Methods

Here, we usedSox2GFP/+mice to isolate the Sox2+ SCs at postnatal day (P)3, P7, P14, and P30 via flow cytometry. Next, we used RNA-seq to determine the transcriptome expression profiles of P3, P7, P14, and P30 SCs. To further analyze the relationships between these age-related and differentially expressed genes in Sox2+ SCs, we performed gene ontology (GO) analysis.

Results

Consistent with previous reports, we also found that the proliferation and HC regeneration ability of isolated Sox2+ SCs significantly decreased as mice aged. We identified numerous genes that are enriched and differentially expressed in Sox2+ SCs at four different postnatal ages, including cell cycle genes, signaling pathway genes, and transcription factors that might be involved in regulating the proliferation and HC differentiation ability of SCs. We thus present a set of genes that might regulate the proliferation and HC regeneration ability of SCs, and these might serve as potential new therapeutic targets for HC regeneration.

Conclusions

In our research, we found several genes that might play an important role in regulating the proliferation and HC regeneration ability of SCs. These datasets are expected to serve as a resource to provide potential new therapeutic targets for regulating the ability of SCs to regenerate HCs in postnatal mammals.
mTORC2 affects the maintenance of the muscle stem cell pool
Authors: Rion Nathalie , Castets Perrine , Lin Shuo , Enderle Leonie , Reinhard Judith R. , Rüegg Markus A.
Published: December 2019

Background

The mammalian target of rapamycin complex 2 (mTORC2), containing the essential protein rictor, regulates cellular metabolism and cytoskeletal organization by phosphorylating protein kinases, such as PKB/Akt, PKC, and SGK. Inactivation of mTORC2 signaling in adult skeletal muscle affects its metabolism, but not muscle morphology and function. However, the role of mTORC2 in adult muscle stem cells (MuSCs) has not been investigated.

Method

Using histological, biochemical, and molecular biological methods, we characterized the muscle phenotype of mice depleted for rictor in the Myf5-lineage (RImyfKO) and of mice depleted for rictor in skeletal muscle fibers (RImKO). The proliferative and myogenic potential of MuSCs was analyzed upon cardiotoxin-induced injury in vivo and in isolated myofibers in vitro.

Results

Skeletal muscle of young and 14-month-old RImyfKO mice appeared normal in composition and function. MuSCs from young RImyfKO mice exhibited a similar capacity to proliferate, differentiate, and fuse as controls. In contrast, the number of MuSCs was lower in young RImyfKO mice than in controls after two consecutive rounds of cardiotoxin-induced muscle regeneration. Similarly, the number of MuSCs in RImyfKO mice decreased with age, which correlated with a decline in the regenerative capacity of mutant muscle. Interestingly, reduction in the number of MuSCs was also observed in 14-month-old RImKO muscle.

Conclusions

Our study shows that mTORC2 signaling is dispensable for myofiber formation, but contributes to the homeostasis of MuSCs. Loss of mTORC2 does not affect their myogenic function, but impairs the replenishment of MuSCs after repeated injuries and their maintenance during aging. These results point to an important role of mTORC2 signaling in MuSC for muscle homeostasis.
Niche differentiation rather than biogeography shapes the diversity and composition of microbiome of Cycas panzhihuaensis
Authors: Zheng Ying , Gong Xun
Published: December 2019

Background

Given their adaptation to nutrient-poor and drought environments, cycads are vital models for plant-microbiome interaction research because they are likely to host an important reservoir of beneficial microbes that may support cycad survival. However, a comprehensive understanding of the diversity and community composition of microbiome associated with different plant compartments as well as bulk soils of cycad species remains elusive.

Method

An extensive investigation of species diversity and community composition of bacterial and fungal microbiome in roots, seeds, unfertilized seeds, ovules, pollens, and soils of Cycas panzhihuaensis L. Zhou & S. Y. Yang has been conducted by high-through sequencing technology. Moreover, principal component analysis (PCA), hierarchical cluster analysis (HCA), and heatmap analysis were applied to test the niche-specific effect and biogeography factor among different sample types of this cycad species.

Results

Highly diverse microbiota and significant variation of community structure were found among different compartments of C. panzhihuaensis. Soils exhibited a remarkable differentiation of bacterial community composition compared to the other five plant organs as revealed by PCA, HCA, and heatmap analyses. Different compartments possessed unique core microbial taxa with Pseudomonadaceae and Nectriaceae shared among them. According to the indicator species analysis, there was almost no differentiation of dominant microbiomes with regard to the geography of the host cycad. Two main transmission models existed in the C. panzhihuaensis.

Conclusions

Each sample type represented a unique niche and hosted a niche-specific core microbial taxa. Contrary to previous surveys, biogeography hardly exerted impact on microbial community variation in this study. The majority of the cycad-associated microbes were horizontally derived from soils and/or air environments with the rest vertically inherited from maternal plants via seeds. This study offers a robust knowledge of plant-microbiome interaction across various plant compartments and soils and lends guidelines to the investigation of adaptation mechanism of cycads in arid and nutrient-poor environments as well as their evolutionary conservation.
Facile aqueous-phase synthesis of Ag–Cu–Pt–Pd quadrometallic nanoparticles
Authors: Tang Zengmin , Yeo Byung Chul , Han Sang Soo , Lee Tae-Jin , Bhang Suk Ho , Kim Woo-Sik , Yu Taekyung
Published: December 2019

Ag–Cu–Pt–Pd quadrometallic nanoparticles which small Pt and Pd nanoparticles were attached on the surface of AgCu Janus nanoparticles were firstly synthesized by sequential reduction of Pt and Pd precursor in the presence of Janus AgCu bimetallic nanoparticles as seeds in an aqueous solution. Even though there was a small amount of Cu2O on the surface, the synthesized nanoparticles were mainly composed of four independent metallic part, not alloy parts. By theoretical calculation and growth mechanism study, we found that different reducing rate between Ag+ and Cu2+ and sequential reduction of Pt and Pd precursors would be key roles for the formation of the quadrometallic nanoparticles.
Metabolic pathway analysis for in silico design of efficient autotrophic production of advanced biofuels
Authors: Unrean Pornkamol , Tee Kang Lan , Wong Tuck Seng
Published: December 2019

Herein, autotrophic metabolism ofCupriavidus necatorH16 growing on CO2, H2and O2gas mixture was analyzed by metabolic pathway analysis tools, specifically elementary mode analysis (EMA) and flux balance analysis (FBA). As case studies, recombinant strains ofC. necatorH16 for the production of short-chain (isobutanol) and long-chain (hexadecanol) alcohols were constructed and examined by a combined tools of EMA and FBA to comprehensively identify the cell’s metabolic flux profiles and its phenotypic spaces for the autotrophic production of recombinant products. The effect of genetic perturbations via gene deletion and overexpression on phenotypic space of the organism was simulated to improve strain performance for efficient bioconversion of CO2to products at high yield and high productivity. EMA identified multiple gene deletion together with controlling gas input composition to limit phenotypic space and push metabolic fluxes towards high product yield, while FBA identified target gene overexpression to debottleneck rate-limiting fluxes, hence pulling more fluxes to enhance production rate of the products. A combination of gene deletion and overexpression resulted in designed mutant strains with a predicted yield of 0.21–0.42 g/g for isobutanol and 0.20–0.34 g/g for hexadecanol from CO2. The in silico-designed mutants were also predicted to show high productivity of up to 38.4 mmol/cell-h for isobutanol and 9.1 mmol/cell-h for hexadecanol under autotrophic cultivation. The metabolic modeling and analysis presented in this study could potentially serve as a valuable guidance for future metabolic engineering ofC. necatorH16 for an efficient CO2-to-biofuels conversion.
Progressive cracking technique for phacoemulsification of superhard cataracts: a case report
Authors: Zhao Yun-e , Li Zhangliang , Chang Pingjun , Wang Dandan , Hu Man
Published: December 2019

Background

Complete nuclear disassembly of superhard cataracts cannot always be achieved by phaco chop, which is considered one of the best techniques for dealing with hard cataracts. We present a phaco chop-progressive cracking technique to divide superhard cataracts completely.

Case presentation

We presented a case of cataract with over Grade V nucleus sclerosis and very low density of corneal endothelial cell (812 cells/mm2). By performing the cataract surgery with our phaco chop-progressive cracking technique, the corneal endothelial cells were well protected and the patient’s visual acuity was markedly improved from finger counting at 40 cm to 20/200 the day after surgery without obvious corneal edema.

Conclusions

Although an initial learning curve was needed, this phaco chop-progressive cracking technique could be of particular benefit to the superhard cataract, especially in patients with low density of corneal endothelial cells.
A pilot study of the duration of GP consultations in Ireland
Authors: Pierse Tom , Barry Luke , Glynn Liam , Quinlan Diarmuid , Murphy Andrew , O’Neill Ciaran
Published: December 2019

Background

General practitioner (GP)-led primary care is the linchpin of health care in Ireland. Reflecting international trends, there are increasing concerns about the sustainability of the current Irish GP service due to an increasing workload. Objective data on the duration of GP consultations are currently not available in Ireland. The objective of this pilot study is to demonstrate how the duration of consultations can be collected, using readily available administrative data.

Methods

Software was developed to extract the duration of GP consultations using the opening and closing of electronic patient records associated with a GP consultation. GP practices (N = 3) comprising 15 GPs were recruited from a university-affiliated research network. A retrospective analysis of GP consultations with patients with diabetes for the 9 years between 2010 and 2018 was used to assess the feasibility of using this system to measure the duration of consultations.

Results

The average duration of a consultation was 14.1 min for the 9 years spanning 2010 to 2018. Patients had an average time between consultations of 99 days.

Conclusions

This pilot study confirms that an administrative data set can be utilised at negligible cost to monitor GP practice consultation workload over time. Our preliminary pilot data show that GP consultation durations among participating practices were longer than the 5–11.7 min reported in the UK and show an increase over the period. Clearly, a larger number of practices and patients are required to substantiate this finding.
UTI − quo vadis? New alternatives to treat uncomplicated urinary tract infections
Authors: Naber Kurt G. , Tandogdu Zafer , Köves Bela , Bonkat Gernot , Wagenlehner Florian
Published: December 2019

Urinary tract infections (UTI) are one of the most common problems in urology clinics. The European Association of Urology (EAU) has been pioneering in its efforts to disseminate the latest clinical findings through the organization of the annual EAU congresses. At this year’s congress (EAU Barcelona 2019), various satellite symposia were organized, focusing on specific issues in the field of urology. "UTI − quo vadis? New alternatives to treat uncomplicated urinary tract infections" was one of the industry-sponsored symposia, organized with the aim of evaluating the current scenario and also throwing light on the paradigm shift in the treatment of acute, uncomplicated lower urinary tract infections (uUTI). Several interlinking topics were presented during this symposium. The topics covered antibiotic resistance, involving a presentation of the current data from the Global Prevalence Study on Infections in Urology (GPIU-study). This discussion was followed by case reports on the impact of antibiotic resistance on the management of patients with UTI/uUTI and treatment options for UTI/uUTI according to current guidelines. The highlight of the symposium was the presentation of very recent data from a gold standard phase III clinical trial (double-blind, double-dummy randomized study), demonstrating the non-inferiority of a herbal medicine (BNO 1045) versus antibiotic therapy (fosfomycin trometamol (FT), as a single dose = 3 g) for the treatment of acute, uncomplicated cystitis.