bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of universal and cell-type specific p53 DNA binding
Authors: Hafner Antonina , Kublo Lyubov , Tsabar Michael , Lahav Galit , Stewart-Ornstein Jacob
Published: February 2020

Background

The tumor suppressor p53 is a major regulator of the DNA damage response and has been suggested to selectively bind and activate cell-type specific gene expression programs. However recent studies and meta-analyses of genomic data propose largely uniform, and condition independent p53 binding and thus question the selective and cell-type dependent function of p53.

Results

To systematically assess the cell-type specificity of p53, we measured its association with DNA in 12 p53 wild-type cancer cell lines, from a range of epithelial linages, in response to ionizing radiation. We found that the majority of bound sites were occupied across all cell lines, however we also identified a subset of binding sites that were specific to one or a few cell lines. Unlike the shared p53-bound genome, which was not dependent on chromatin accessibility, the association of p53 with these atypical binding sites was well explained by chromatin accessibility and could be modulated by forcing cell state changes such as the epithelial-to-mesenchymal transition.

Conclusions

Our study reconciles previous conflicting views in the p53 field, by demonstrating that although the majority of p53 DNA binding is conserved across cell types, there is a small set of cell line specific binding sites that depend on cell state.
Oxygen therapy in patients with ST elevation myocardial infarction based on the culprit vessel: results from the randomized controlled SOCCER trial
Authors: Mokhtari Arash , Akbarzadeh Mahin , Sparv David , Bhiladvala Pallonji , Arheden Håkan , Erlinge David , Khoshnood Ardavan
Published: February 2020

Background

Oxygen (O2) treatment has been a cornerstone in the treatment of patients with myocardial infarction. Recent studies, however, state that supplemental O2therapy may have no effect or harmful effects in these patients. The aim of this study was thus to evaluate the effect of O2therapy in patients with ST Elevation Myocardial Infarction (STEMI) based on the culprit vessel; Left Anterior Descending Artery (LAD) or Non-LAD.

Methods

This was a two-center, investigator-initiated, single-blind, parallel-group, randomized controlled trial at the Skåne university hospital, Sweden. A simple computer-generated randomization was used. Patients were either randomized to standard care with O2therapy (10 l/min) or air until the end of the primary percutaneous coronary intervention. The patients underwent a Cardiac Magnetic Resonance Imaging (CMRI) days 2–6. The main outcome measures were Myocardium at Risk (MaR), Infarct Size (IS) and Myocardial Salvage Index (MSI) as measured by CMRI, and median high-sensitive troponin T (hs-cTnT).

Results

A total of 229 patients were assessed for eligibility, and 160 of them were randomized to the oxygen or air arm. Because of primarily technical problems with the CMRI, 95 patients were included in the final analyses; 46 in the oxygen arm and 49 in the air arm. There were no significant differences between patients with LAD and Non-LAD as culprit vessel with regard to their allocation (oxygen or air) with regards to MSI, MaR, IS and hs-cTnT.

Conclusion

The results indicate that the location of the culprit vessel has probably no effect on the role of supplemental oxygen therapy in STEMI patients.

Trial registration

Swedish Medical Products Agency (EudraCT No. 2011–001452-11) and ClinicalTrials.gov Identifier (NCT01423929).
Uric acid induced hepatocytes lipid accumulation through regulation of miR-149-5p/FGF21 axis
Authors: Chen Shenghui , Chen Dan , Yang Hua , Wang Xinyu , Wang Jinghua , Xu Chengfu
Published: February 2020

Background

Hyperuricemia is a major risk for non-alcoholic fatty liver disease. However, the mechanisms for this phenomenon are not fully understood. This study aimed to investigate whether microRNAs mediated the pathogenic effects of uric acid on non-alcoholic fatty liver disease.

Methods

Microarray was used to determine the hepatic miRNA expression profiles of male C57BL/6 mice fed on standard chow diet, high fat diet (HFD), and HFD combined with uric acid-lowering therapy by allopurinol. We validated the expression of the most significant differentially expressed microRNAs and explored its role and downstream target in uric acid-induced hepatocytes lipid accumulation.

Results

Microarray analysis and subsequent validation showed that miR-149-5p was significantly up-regulated in the livers of HFD-fed mice, while the expression was down-regulated by allopurinol therapy. MiR-149-5p expression was also significantly up-regulated in uric acid-stimulated hepatocytes. Over-expression of miR-149-5p significantly aggregated uric acid-induced triglyceride accumulation in hepatocytes, while inhibiting miR-149-5p ameliorated the triglyceride accumulation. Luciferase report assay confirmed that FGF21 is a target gene of miR-149-5p. Silencing FGF21 abolished the ameliorative effects of miR-149-5p inhibitor on uric acid-induced hepatocytes lipid accumulation, while overexpression of FGF21 prevented the lipid accumulation induced by miR-149-5p mimics.

Conclusions

Uric acid significantly up-regulated the expression of miR-149-5p in hepatocytes and induced hepatocytes lipid accumulation via regulation of miR-149-5p/FGF21 axis.
Impact of urine and mixed incontinence on long-term care preference: a vignette-survey study of community-dwelling older adults
Authors: Carvalho Nicolas , Fustinoni Sarah , Abolhassani Nazanin , Blanco Juan Manuel , Meylan Lionel , Santos-Eggimann Brigitte
Published: February 2020

Background

In view of population aging, a better knowledge of factors influencing the type of long-term care (LTC) among older adults is necessary. Previous studies reported a close relationship between incontinence and institutionalization, but little is known on opinions of older citizens regarding the most appropriate place of care. This study aimed at evaluating the impact of urine and/or fecal incontinence on preferences of community–dwelling older citizens.

Methods

We derived data from the Lausanne cohort 65+, a population-based study of individuals aged from 68 to 82 years. A total of 2974 community-dwelling persons were interviewed in 2017 on the most appropriate place of LTC delivery for three vignettes displaying a fixed level of disability with varying degrees of incontinence (none, urinary, urinary and fecal). Multinomial logistic regression analyses explored the effect of respondents’ characteristics on their opinion according to Andersen’s model.

Results

The level of incontinence described in vignettes strongly determined the likelihood of considering institutional care as most appropriate. Respondents’ characteristics such as age, gender, educational level, being a caregiver, knowledge of shelter housing or feeling supported by family influenced LTC choices. Self-reported incontinence and other indicators of respondents’ need, however, had no significant independent effect.

Conclusion

Among older community-dwelling citizens, urinary and fecal incontinence play a decisive role in the perception of a need for institutionalization. Prevention and early initiation of support for sufferers may be a key to prevent this need and ensure familiar surrounding as long as possible.
Spatial clustering of suicide mortality and associated community characteristics in Kanagawa prefecture, Japan, 2011–2017
Authors: Yamaoka Kazue , Suzuki Masako , Inoue Mariko , Ishikawa Hirono , Tango Toshiro
Published: February 2020

Background

Suicide mortality is high in Japan and early interventional strategies to solve that problem are needed. An accurate evaluation of the regional status of current suicide mortality would be useful for community interventions. A few studies in Kanagawa prefecture, located next to Tokyo and with the second largest population in Japan, have identified spatial clusters of suicide mortality at regional levels. This study examined spatial clustering and clustering over time of such events using spatial data from regional statistics on suicide deaths.

Methods

Data were obtained from regional statistics (58 regions in Kanagawa prefecture) of the National Vital Statistics of Japan from 2011 to 2017. The standardized mortality ratio (SMR) and Empirical Bayes estimator for the SMR (EBSMR) were used as measures. Spatial clusters were examined by Kulldorff’s circular spatial scan statistic, Tango-Takahashi’s flexible spatial scan statistic and Tango’s test. Linear regression and conditional autoregressive (CAR) models were used not only to adjust for covariates but also to estimate regional effects. The analyses were conducted for each year, inclusive.

Results

Among male suicide deaths, being unemployed (50%) was most frequently related to suicide while among female health problem (50%) were frequent. Spatial clusters with significance detected by FlexScan, SatScan and Tango’s test were few and varied somewhat according to the method used. Spatial clusters were detected in some regions including Kawasaki ward after adjustment by covariates. By the linear regression models, selected variables with significance were different between the sexes. For males, unemployment, family size, and proportion of higher education were detected for several of the years studied while for females, family size and divorce rate were detected over this period. These variables were also observed by the CAR model with 5 covariates. Regional effects were much clearer by considering the spatial parameter for both males and females and especially, Kawasaki ward was detected as a high risk region in many years.

Conclusion

The present results detected some spatial clustering of suicide deaths within certain regions. Factors related to suicide deaths were also indicated. These results would provide important information in policy making for suicide prevention.
Overview of international naturopathic practice and patient characteristics: results from a cross-sectional study in 14 countries
Authors: Steel Amie , Foley Hope , Bradley Ryan , Van De Venter Claudine , Lloyd Iva , Schloss Janet , Wardle Jon , Reid Rebecca
Published: February 2020

Background

Naturopathy is a distinct system of traditional and complementary medicine recognized by the World Health Organization and defined by its philosophic approach to patient care, rather than the treatments used by practitioners. Worldwide, over 98 countries have practicing naturopaths, representing 36% of all countries and every world region. The contributions of naturopaths to healthcare delivery services internationally has not been previously examined. Thus, the primary intention of this research was to conduct an international survey of naturopathic practice and patient characteristics in order to gain insight to the breadth of their practices and the type of clinical conditions routinely encountered.

Methods

The cross-sectional study was conducted in naturopathic clinics in 14 countries within 4 world regions including the European (Portugal, United Kingdom, Switzerland, Spain), Americas (Canada, United States, Chile, Brazil), Western Pacific (Hong Kong, Australia, New Zealand) and African (South Africa). Naturopathic practitioners in each country were invited to prospectively complete an online survey for 20 consecutive cases. The survey was administered in four languages.

Results

A total of 56 naturopaths from 14 countries participated in the study, providing a mean of 15.1 cases each (SD 7.6) and 851 cases in total. Most patients were female (72.6%) and all age categories were represented with a similar proportion for 36–45 years (20.2%), 46–55 years (19.5%), and 56–65 years (19.3%). A substantial majority (75%) of patients were considered by the participant to be presenting with chronic health conditions. The most prevalent category of health conditions were musculoskeletal (18.5%), gastrointestinal (12.2%), and mental illness (11.0%). The most common treatment categories prescribed or recommended to patients by the participants were dietary changes (60.5%), lifestyle and behaviour changes (56.9%), herbal medicines (54.2%) and nutritional supplements (52.1%). Many patients were known by participants to be receiving care from a general practitioner (43.2%) or a specialist medical practitioner (27.8%).

Conclusions

Naturopathic practitioners provide health care for diverse health conditions in patients in different age groups. The global population would benefit from researchers and policy makers paying closer attention to the potential risks, benefits, challenges and opportunities of the provision of naturopathic care within the community.
Monitoring stance towards vaccination in twitter messages
Authors: Kunneman Florian , Lambooij Mattijs , Wong Albert , Bosch Antal van den , Mollema Liesbeth
Published: February 2020

Background

We developed a system to automatically classify stance towards vaccination in Twitter messages, with a focus on messages with a negative stance. Such a system makes it possible to monitor the ongoing stream of messages on social media, offering actionable insights into public hesitance with respect to vaccination. At the moment, such monitoring is done by means of regular sentiment analysis with a poor performance on detecting negative stance towards vaccination. For Dutch Twitter messages that mention vaccination-related key terms, we annotated their stance and feeling in relation to vaccination (provided that they referred to this topic). Subsequently, we used these coded data to train and test different machine learning set-ups. With the aim to best identify messages with a negative stance towards vaccination, we compared set-ups at an increasing dataset size and decreasing reliability, at an increasing number of categories to distinguish, and with different classification algorithms.

Results

We found that Support Vector Machines trained on a combination of strictly and laxly labeled data with a more fine-grained labeling yielded the best result, at an F1-score of 0.36 and an Area under the ROC curve of 0.66, considerably outperforming the currently used sentiment analysis that yielded an F1-score of 0.25 and an Area under the ROC curve of 0.57. We also show that the recall of our system could be optimized to 0.60 at little loss of precision.

Conclusion

The outcomes of our study indicate that stance prediction by a computerized system only is a challenging task. Nonetheless, the model showed sufficient recall on identifying negative tweets so as to reduce the manual effort of reviewing messages. Our analysis of the data and behavior of our system suggests that an approach is needed in which the use of a larger training dataset is combined with a setting in which a human-in-the-loop provides the system with feedback on its predictions.
Dietary inclusion of Peptiva, a peptide-based feed additive, can accelerate the maturation of the fecal bacterial microbiome in weaned pigs
Authors: Poudel Prakash , Levesque Crystal L. , Samuel Ryan , St-Pierre Benoit
Published: February 2020

Background

Weaning is one of the most critical transition stages of the swine production cycle, as the piglet gut physiology and microbiome need to rapidly adapt to changes in diet and environmental conditions. Based on their potential for producing a vast array of bioactive molecules, peptide formulations represent a largely untapped source of compounds that could be developed into feed additives to benefit animal health and nutrition. In this context, a commercial-scale nursery trial was performed to evaluate the impact of low inclusion of a peptide-based feed additive (Peptiva, Vitech Bio-Chem Corporation) on the performance and fecal microbiome of weaned pigs.

Results

While no significant differences in body weight, daily gain, daily feed intake nor gain:feed were observed between control and treatment animals (P > 0.05), an effect of Peptiva on the fecal bacterial composition of weaned pigs was observed. The first main observation was that the fecal bacterial profiles from pigs fed Control-Phase II and Control Phase III diets were found to be very distinct, suggesting that a transition or succession stage had occurred between the two phases. Lactobacilli, represented by four main OTUs (Ssd-00002, Ssd-00019, Ssd-00025, and Ssd-00053), were more abundant at the end of Phase II (P < 0.05), while Streptococci, mostly represented by OTUs Ssd-00039 and Ssd-00048, were in higher abundance at the end of Phase III (P < 0.05). Secondly, the fecal bacterial composition from pigs fed Peptiva Phase II diets showed similarities to both Control-Phase II and Control Phase III samples, while there was no difference in fecal bacterial composition between Control-Phase III and Peptiva Phase III samples. For instance, OTUs Ssd-00019,and Ssd-00053 were in lower abundance in Peptiva Phase II samples compared to Control Phase II (P < 0.05), but no significant difference was observed in the abundance of these two OTUs when comparing Peptiva Phase II to Control Phase III (P > 0.05).

Conclusions

Together, these results suggest that Peptiva can modulate the composition of the swine microbiome during a specific window of the nursery stage, potentially by accelerating its maturation.
Developing an experimental necrotic enteritis model in turkeys - the impact of Clostridium perfringens, Eimeria meleagrimitis and host age on frequency of severe intestinal lesions
Authors: Hardy Simon P. , Benestad Sylvie L. , Hamnes Inger Sofie , Moldal Torfinn , David Bruce , Barta John R. , Reperant Jean-Michel , Kaldhusdal Magne
Published: February 2020

Background

Necrotic enteritis is a significant problem to the poultry industry globally and, in Norway up to 30% of Norwegian turkey grow-outs can be affected. However, despite an awareness that differences exist between necrotic enteritis in chickens and turkeys, little information exists concerning the pathogenesis, immunity, microbiota or experimental reproduction of necrotic enteritis in turkeys. In particular, it is important to determine the appearance of the gross lesions, the age dependency of the disease and the role of netB toxin of Clostridium perfringens. To this end, we report our findings in developing an in vivo experimental model of necrotic enteritis in turkeys.

Results

A four tier (0–3) scoring system with clearly defined degrees of severity of macroscopic intestinal lesions was developed, based on 2312 photographic images of opened intestines from 810 B.U.T. 10 or B.U.T. Premium turkeys examined in nine experiments. Loss of macroscopically recognizable villi in the anterior small intestine was established as the defining lesion qualifying for a score 3 (severe intestinal lesions). The developed scoring system was used to identify important factors in promoting high frequencies of turkeys with severe lesions: a combined Eimeria meleagrimitis and Clostridium perfringens challenge, challenge at five rather than 3 weeks of age, the use of an Eimeria meleagrimitis dose level of at least 5000 oocysts per bird and finally, examination of the intestines of 5-week-old turkeys at 125 to 145 h after Eimeria meleagrimitis inoculation. Numbers of oocysts excreted were not influenced by Clostridium perfringens inoculation or turkey age. Among three different lesion score outcomes tested, frequency of severe lesions proved superior in discriminating between impact of four combinations of Clostridium perfringens inoculation and turkey age at challenge.

Conclusions

This study provides details for the successful establishment of an in vivo model of necrotic enteritis in turkeys.
Engineering yeast artificial core promoter with designated base motifs
Authors: Liu Rui , Liu Lanqing , Li Xia , Liu Duo , Yuan Yingjin
Published: February 2020

Background

Synthetic biology requires toolbox of promoters to finely tune gene expression levels for building up efficient cell factories. Yeast promoters owned variable core promoter regions between the TATA-box and transcriptional starting site (TSS) at the length mostly around 20–80 bases. This region allowed flexible design of artificial promoter but potentially demand special base motifs to maintain or enhance the promoter’s strength.

Results

Here, we designed and screened the base motifs and tested the activities of yeast artificial core promoters. Different 30 bases of artificial sequences led to variable expression levels of CrtY enzyme which determined the lycopene–carotene compositions, represented in the colony-color spectrum of red–orange–yellow. The upstream sequences of two strong promoter PEXP1 and PGPD and two starting strains with distinguishable lycopene production levels were utilized to characterize the promoter sequences. Different partition designs of T-rich or G/C-rich base motifs led to distinguishable colony-color distributions. Finally, we screened a champion promoter with a highest 5.5-fold enhancement of lycopene–carotene transformation. Another selected promoter generated a highest beta-carotene production as 7.4 mg/g DCW.

Conclusions

This work offered an approach to redesign promoter with artificial sequences. We concluded that the core promoter region could be designated as 30 bases and different base motifs would enhance or weaken the promoter’s strength. Generally, more T-rich elements, higher %T and lower G/C percentage were beneficial to enhance the strength of artificial core promoter.
Proteome interrogation using gold nanoprobes to identify targets of arctigenin in fish parasites
Authors: Tu Xiao , Tan Xiaoping , Qi Xiaozhou , Huang Aiguo , Ling Fei , Wang Gaoxue
Published: February 2020

Gold nanoparticles (GNPs) are one of the most widely used nanomaterials in various fields. Especially, the unique chemical and physical properties make them as the promising candidates in drug target identification, unfortunately, little is known about their application in parasites. In this paper, GNPs were employed as new solid support to identify drug targets of natural bioactive compound arctigenin (ARG) against fish monogenean parasite Gyrodactylus kobayashi. Before target identification, GNPs with ARG on the surface showed the ability to enter the live parasites even the nucleus or mitochondria, which made the bound compounds capable of contacting directly with target proteins located anywhere of the parasites. At the same time, chemically modified compound remained the anthelminthic efficacy against G. kobayashii. The above results both provide assurance on the reliability of using GNPs for drug target-binding specificity. Subsequently, by interrogating the cellular proteome in parasite lysate, myosin-2 and UNC-89 were identified as the potential direct target proteins of ARG in G. kobayashii. Moreover, results of RNA-seq transcriptomics and iTRAQ proteomics indicated that myosin-2 expressions were down-regulated after ARG bath treatment both in transcript and protein levels, but for UNC-89, only in mRNA level. Myosin-2 is an important structural muscle protein expressed in helminth tegument and its identification as our target will enable further inhibitor optimization towards future drug discovery. Furthermore, our findings demonstrate the power of GNPs to be readily applied to other parasite drugs of unknown targets, facilitating more broadly therapeutic drug design in any pathogen or disease model.
Macrophage MSR1 promotes the formation of foamy macrophage and neuronal apoptosis after spinal cord injury
Authors: Kong Fan-Qi , Zhao Shu-Jie , Sun Peng , Liu Hao , Jie Jian , Xu Tao , Xu An-Di , Yang Ya-Qing , Zhu Ye , Chen Jian , Zhou Zheng , Qian Ding-Fei , Gu Chang-Jiang , Chen Qi , Yin Guo-Yong , Zhang Han-Wen , Fan Jin
Published: February 2020

Background

A sustained inflammatory response following spinal cord injury (SCI) contributes to neuronal damage, inhibiting functional recovery. Macrophages, the major participants in the inflammatory response, transform into foamy macrophages after phagocytosing myelin debris, subsequently releasing inflammatory factors and amplifying the secondary injury. Here, we assessed the effect of macrophage scavenger receptor 1 (MSR1) in phagocytosis of myelin debris after SCI and explained its possible mechanism.

Methods

The SCI model was employed to determine the critical role of MSR1 in phagocytosis of myelin debris in vivo. The potential functions and mechanisms of MSR1 were explored using qPCR, western blotting, and immunofluorescence after treating macrophages and RAW264.7 with myelin debris in vitro.

Results

In this study, we found improved recovery from traumatic SCI in MSR1-knockout mice over that in MSR1 wild-type mice. Furthermore, MSR1 promoted the phagocytosis of myelin debris and the formation of foamy macrophage, leading to pro-inflammatory polarization in vitro and in vivo. Mechanistically, in the presence of myelin debris, MSR1-mediated NF-κB signaling pathway contributed to the release of inflammatory mediators and subsequently the apoptosis of neurons.

Conclusions

Our study elucidates a previously unrecognized role of MSR1 in the pathophysiology of SCI and suggests that its inhibition may be a new treatment strategy for this traumatic condition.
A novel role of NLRP3-generated IL-1β in the acute-chronic transition of peripheral lipopolysaccharide-elicited neuroinflammation: implications for sepsis-associated neurodegeneration
Authors: Zhao Zhan , Wang Yubao , Zhou Ran , Li Yi , Gao Yun , Tu Dezhen , Wilson Belinda , Song Sheng , Feng Jing , Hong Jau-Shyong , Yakel Jerrel L.
Published: February 2020

Background

Sepsis-associated acute brain inflammation, if unresolved, may cause chronic neuroinflammation and resultant neurodegenerative diseases. However, little is known how the transition from acute to chronic neuroinflammation, which is critical for the following progressive neurodegeneration, occurs in sepsis. The goal of this study was to investigate potential immune factors regulating the transition process using a widely used endotoxemia LPS mouse model. This model shows distinct acute and chronic phases of neuroinflammation and recapitulates many cardinal features of Parkinson’s disease, thus, providing a unique opportunity for studying phase transition of neuroinflammation.

Methods

C57BL/6 J, NLRP3−/−, and IL-1R1−/− mice were employed. Mild and severe endotoxemia were produced by LPS ip injection at 1 or 5 mg/kg. Neuroinflammation in vitro and in vivo was assessed with proinflammatory cytokine expression by qPCR or ELISA and microglial activation by immunohistochemical analysis. Neurodegeneration was measured by manual and stereological counts of nigral dopaminergic neurons and immunohistochemical analysis of protein nitrosylation and α-synuclein phosphorylation.

Results

LPS-elicited initial increases in mouse brain mRNA levels of TNFα, IL-6, IL-1β, and MCP-1, and nigral microglial activation were not dose-related. By contrast, the delayed increase in brain mature IL-1β levels was dependent on LPS doses and protracted nigral microglial activation was only observed in high dose of LPS-treated mice. LPS-elicited increase in brain mature IL-1β but not IL-1α level was NLRP3-dependent. After high dose LPS treatment, deficiency of NLRP3 or IL-1R1 did not prevent the initiation of acute neuroinflammation but abolished chronic neuroinflammation. Genetic or pharmacological inhibition of the NLRP3-IL-1β axis repressed LPS-stimulated upregulation of chronic neuroinflammatory mediators including MHC-II, NOX2, and Mac1, and protected dopaminergic neurons. Ten months after LPS-elicited severe endotoxemia, nigral persisted microglial activation, elevated nitrosylated proteins and phosphorylated α-synuclein, and significant neuronal degeneration developed in wild-type mice but not in NLRP3−/− or IL-1R1−/− mice.

Conclusions

This study uncovers a novel role of the NLRP3-IL-1β signaling pathway in gauging the severity of sepsis-associated inflammation and determining whether acute neuroinflammation will resolve or transition to low grade chronic neuroinflammation. These findings also provide novel targets for developing therapy for severe systemic infection-related neurodegeneration.
Effects of manual therapies on stability in people with musculoskeletal pain: a systematic review
Authors: Kendall Julie C. , Vindigni Dein , Polus Barbara I. , Azari Michael F. , Harman Samantha C.
Published: February 2020

Introduction

Chronic musculoskeletal pain is associated with reduced balance performance and falls risk. Manual therapies are commonly used interventions for musculoskeletal pain. There is emerging evidence that manual therapies may improve balance. The aim of this systematic review was to examine the effectiveness of manual therapies for musculoskeletal pain on measures of static and dynamic stability.

Methods

Six electronic databases were searched using pre-defined eligibility criteria and two independent reviewers assessed all identified records. Risk of bias was assessed using the 12-item Cochrane Risk of Bias assessment by two authors independently and any discrepancies resolved through consensus. Meta-analysis was conducted when three or more studies used the same outcome measures including gait speed, timed up and go test, step test and sit-to-stand test.

Results

Twenty-six studies were included in the analysis. Both spinal and extremity musculoskeletal pain conditions were represented. Manual therapies included manipulation, mobilisation and massage. The most common intervention compared to manual therapy was exercise. Outcome measures included both clinical and objective measures of stability. Overall the risk of bias was reported as generally low or unclear.

Conclusion

Improvement in stability measures were reported in studies comparing manual therapy in the short term, but not long-term follow-up. There was no clear association between significant pain reduction and measures of stability. Further prospective studies are recommended to investigate whether manual therapies should be part of an integrative healthcare plan for risk of falls management and when a transition from manual therapy to more active interventions should occur for long term management.
Colorimetric and spectrophotometric measurements of orthodontic thermoplastic aligners exposed to various staining sources and cleaning methods
Authors: Bernard Gabrielle , Rompré Pierre , Tavares Jason Robert , Montpetit Andrée
Published: February 2020

Background

Manufacturers of orthodontic aligners suggest that users remove appliances every time they consume solid foods or any drink (except water). This is to avoid a color change within the clear thermoplastic material of which they are made. However, limited quantitative evidence exists to guide users and practitioners in this regard. Herein, we evaluated the color stability of the polymer forming three different American brands of aligners and the stain-removal potential of two cleansers to provide such guidelines.

Methods

The removable appliances (300 specimens, 100 per brand) were exposed to different staining agents common in a regular diet (coffee, black tea, red wine, cola) or to a control solution in vitro over 12 h or 7 days. The three brands evaluated were Invisalign®, ClearCorrect® and Minor Tooth Movement®. These were then cleaned by using either Invisalign® cleaning crystals or the Cordless Sonic Cleaner combined with a Retainer Brite® tablet. The CIELAB color space approach was used to compare color changes (ΔE) in aligners before immersion (T0), after a 12-h exposure (T1), after a 7-day exposure (T2) and after cleaning (T3). Statistical methods (Levene’s test, ANOVA, Brunner-Langer model, Tukey’s range test and t-test) were used to identify interactions between the brands themselves or between the brands and the cleaning methods. Statistical analyses were performed at the .05 significance level.

Results

A 12-h or 7-day exposure to instant coffee or red wine significantly colored the Invisalign® aligners compared to the two other brands. Black tea created an important extrinsic color change for all three brands after 7 days. Clinically, both cleaning methods showed a better efficacy in removing stains from black tea compared to other staining agents.

Conclusions

The Invisalign® aligners were more prone to pigmentation than the ClearCorrect® or the Minor Tooth Movement® devices after an exposure to coffee or red wine. Black tea caused important stains on the surface of the three tested brands. Both cleansing methods performed similarly.
Radiotherapy quality assurance for mesorectum treatment planning within the multi-center phase II STAR-TReC trial: Dutch results
Authors: van den Ende Roy P. J. , Peters Femke P. , Harderwijk Ernst , Rütten Heidi , Bouwmans Liza , Berbee Maaike , Canters Richard A. M. , Stoian Georgiana , Compagner Kim , Rozema Tom , de Smet Mariska , Intven Martijn P. W. , Tijssen Rob H. N. , Theuws Jacqueline , van Haaren Paul , van Triest Baukelien , Eekhout Dave , Marijnen Corrie A. M. , van der Heide Uulke A. , Kerkhof Ellen M.
Published: February 2020

Background

The STAR-TReC trial is an international multi-center, randomized, phase II study assessing the feasibility of short-course radiotherapy or long-course chemoradiotherapy as an alternative to total mesorectal excision surgery. A new target volume is used for both (chemo)radiotherapy arms which includes only the mesorectum. The treatment planning QA revealed substantial variation in dose to organs at risk (OAR) between centers. Therefore, the aim of this study was to determine the treatment plan variability in terms of dose to OAR and assess the effect of a national study group meeting on the quality and variability of treatment plans for mesorectum-only planning for rectal cancer.

Methods

Eight centers produced 25 × 2 Gy treatment plans for five cases. The OAR were the bowel cavity, bladder and femoral heads. A study group meeting for the participating centers was organized to discuss the planning results. At the meeting, the values of the treatment plan DVH parameters were distributed among centers so that results could be compared. Subsequently, the centers were invited to perform replanning if they considered this to be necessary.

Results

All treatment plans, both initial planning and replanning, fulfilled the target constraints. Dose to OAR varied considerably for the initial planning, especially for dose levels below 20 Gy, indicating that there was room for trade-offs between the defined OAR. Five centers performed replanning for all cases. One center did not perform replanning at all and two centers performed replanning on two and three cases, respectively. On average, replanning reduced the bowel cavity V20Gy by 12.6%, bowel cavity V10Gy by 22.0%, bladder V35Gy by 14.7% and bladder V10Gy by 10.8%. In 26/30 replanned cases the V10Gy of both the bowel cavity and bladder was lower, indicating an overall lower dose to these OAR instead of a different trade-off. In addition, the bowel cavity V10Gy and V20Gy showed more similarity between centers.

Conclusions

Dose to OAR varied considerably between centers, especially for dose levels below 20 Gy. The study group meeting and the distribution of the initial planning results among centers resulted in lower dose to the defined OAR and reduced variability between centers after replanning.

Trial registration

The STAR-TReC trial, ClinicalTrials.gov Identifier: NCT02945566. Registered 26 October 2016, https://clinicaltrials.gov/ct2/show/NCT02945566).
Volumetric modulated arc therapy (VMAT) for hippocampal-avoidance whole brain radiation therapy: planning comparison with Dual-arc and Split-arc partial-field techniques
Authors: Yuen Adams Hei Long , Wu Po Man , Li Alex Kai Leung , Mak Philip Chung Yin
Published: February 2020

Background

Although whole brain radiation therapy (WBRT) provides palliation and prophylaxis, reduces local recurrence probability and improves overall survival, it is evident that WBRT is associated with neurocognitive deficits due to radiation induced damage of the hippocampus. Therefore, minimizing hippocampal dose to the least possible level is of high clinical relevance. In dual-arc conventional volumetric modulated arc therapy (dac-VMAT), the large irradiation field for whole brain planned target volume (PTV) requires a wide jaw opening in which substantial low dose volume to the hippocampus may be produced due to suboptimal multi-leaf collimator (MLC) movements. The present study investigates the potential of a radiation therapy technique with split-arc and reduced field size, namely split-arc partial-field volumetric modulated arc therapy (sapf-VMAT) to spare the hippocampus during WBRT.

Methods

Computed tomography and magnetic resonance images of 20 patients with brain metastases were retrieved in this retrospective planning study. The hippocampus was manually delineated by single radiation oncologist strictly following the RTOG 0933 atlas definition. Plans delivering 30 Gy in 10 fractions were generated for each patient using dac-VMAT and sapf-VMAT. Dosimetric parameters from both techniques were compared by paired t-test.

Results

The results demonstrated that radiation dose to the hippocampus was significantly reduced using sapf-VMAT relative to dac-VMAT plans. sapf-VMAT (7.86Gy, p = 0.001) had significantly lowered average D100% compared to dac-VMAT (9.23 Gy). Decrease in hippocampus Dmax using sapf-VMAT (13.23 Gy, p = 0.001) was statistically significant when compared to dac-VMAT (16.33 Gy). The resulting mean dose to the hippocampus was 9.16 Gy for the for sapf-VMAT. Mean dose of sapf-VMAT was significantly lower than dac-VMAT (10.85 Gy, p < 0.05). In both eyes, sapf-VMAT demonstrated significantly lower Dmean compared to dac-VMAT (p < 0.05). Whole brain PTV coverage was not compromised in both techniques.

Conclusion

sapf-VMAT has demonstrated significant dose reduction to the hippocampus and both eyes compared to dac-VMAT.
A proposal for a comprehensive approach to infections across the surgical pathway
Authors: Sartelli Massimo , Pagani Leonardo , Iannazzo Stefania , Moro Maria Luisa , Viale Pierluigi , Pan Angelo , Ansaloni Luca , Coccolini Federico , D’Errico Marcello Mario , Agreiter Iris , Amadio Nespola Giorgio , Barchiesi Francesco , Benigni Valeria , Binazzi Raffaella , Cappanera Stefano , Chiodera Alessandro , Cola Valentina , Corsi Daniela , Cortese Francesco , Crapis Massimo , Cristini Francesco , D’Arpino Alessandro , De Simone Belinda , Di Bella Stefano , Di Marzo Francesco , Donati Abele , Elisei Daniele , Fantoni Massimo , Ferrari Anna , Foghetti Domitilla , Francisci Daniela , Gattuso Gianni , Giacometti Andrea , Gesuelli Guido Cesare , Marmorale Cristina , Martini Enrica , Meledandri Marcello , Murri Rita , Padrini Daniela , Palmieri Dalia , Pauri Paola , Rebagliati Carla , Ricchizzi Enrico , Sambri Vittorio , Schimizzi Anna Maria , Siquini Walter , Scoccia Loredana , Scoppettuolo Giancarlo , Sganga Gabriele , Storti Nadia , Tavio Marcello , Toccafondi Giulio , Tumietto Fabio , Viaggi Bruno , Vivarelli Marco , Tranà Cristian , Raso Melina , Labricciosa Francesco Maria , Dhingra Sameer , Catena Fausto
Published: February 2020

Despite evidence supporting the effectiveness of best practices in infection prevention and management, many healthcare workers fail to implement them and evidence-based practices tend to be underused in routine practice. Prevention and management of infections across the surgical pathway should always focus on collaboration among all healthcare workers sharing knowledge of best practices. To clarify key issues in the prevention and management of infections across the surgical pathway, a multidisciplinary task force of experts convened in Ancona, Italy, on May 31, 2019, for a national meeting. This document represents the executive summary of the final statements approved by the expert panel.
Gene polymorphisms and expression levels of interleukin-6 and interleukin-10 in lumbar disc disease: a meta-analysis and immunohistochemical study
Authors: Guan Yewen , Wang Siting , Wang Jiaqi , Meng Dihua , Wu Huihong , Wei Qingjun , Jiang Hua
Published: February 2020

Background

To investigate the association between interleukin-6 (IL-6) (rs1800795, rs1800796, rs1800797, rs13306435, rs2069849) and interleukin-10 (IL-10) (rs1800871, rs1800896) gene polymorphisms, expression levels, and lumbar disc disease (LDD).

Methods

We conducted a literature research on PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) until February 28, 2019. We included all case-control studies about the association between IL-6 and IL-10 gene polymorphisms and LDD. The odds ratio (OR) and 95% confidence interval (CI) were calculated to estimate the strength of association. Statistical analysis was conducted by Review Manager (RevMan) 5.3 software. Furthermore, immunohistochemistry (IHC) and RT-PCR were performed to evaluate IL-6 and IL-10 expressions in the normal and degenerated disc.

Results

A total of 6 studies, involving 1456 cases and 1611 controls, were included in this meta-analysis. G alleles of rs1800795 and rs1800797 in the IL-6 gene were significantly associated with LDD (rs1800795: G vs. C, OR = 1.38, 95% CI = 1.16–1.64, P = 0.0002; rs1800797: G vs. A, OR = 1.35, 95% CI = 1.14–1.61, P = 0.0006). Begg’s funnel plot and Egger’s tests did not show any evidence of publication bias. IL-6 expression and IL-6 mRNA levels were significantly increased in the degenerated disc compared with those in the normal disc (IL-6 immunopositive cells, 73.68 ± 10.99% vs. 37.23 ± 6.42%, P < 0.001).

Conclusions

IL-6 gene polymorphisms (rs1800795 and rs1800797) were significantly associated with susceptibility to LDD. A high expression level of IL-6 may be an important risk factor for LDD.
Recognizable neonatal clinical features of aplasia cutis congenita
Authors: Schierz Ingrid Anne Mandy , Giuffrè Mario , Del Vecchio Antonello , Antona Vincenzo , Corsello Giovanni , Piro Ettore
Published: February 2020

Background

Aplasia cutis congenita (ACC), classified in nine groups, is likely to be underreported, since milder isolated lesions in wellbeing newborns could often be undetected, and solitary lesions in the context of polymalformative syndromes could not always be reported. Regardless of form and cause, therapeutic options have in common the aim to restore the deficient mechanical and immunological cutaneous protection and to limit the risk of fluid leakage or rupture of the exposed organs. We aimed to review our institutional prevalence, comorbidities, treatment and outcome of newborns with ACC.

Methods

We conducted a retrospective study including all newborns affected by ACC and admitted at the University Mother-Child Department from October 2010 to October 2019. Anthropometric and clinical characteristics of ACC1 versus a non-isolated ACC group were analyzed.

Results

We encountered 37 newborns, 16 with ACC1 versus 21 with non-isolated ACC. The incidence rate of 0.1% in ACC1 was higher than expected, while 19% of cases showed intrafamilial autosomal dominant transmission. Higher birth weight centile, though lower than reference population, being adequate for gestational age, normal Apgar score and euglycemia characterizing ACC1 resulted associated to a rapid tissue regeneration. Non-isolated ACC, in relation to concomitant congenital anomalies and higher prematurity rate, showed more surgical and medical complications along with the risk of neonatal death. Specifically, newborns with ACC4 were characterized by the frequent necessity of abdominal wall defect repair, responsible for the occurrence of an abdominal compartment syndrome.

Conclusion

Prompt carefully assessment of the newborn with ACC in order to exclude concomitant other congenital malformations, provides clues to the underlying pathophysiology, and to the short-term prognosis. Family should be oriented toward identification of other family members affected by similar pathology, while obstetric history should exclude initial multiple pregnancy with death of a co-twin, placental anomalies and drug assumption. Molecular-genetic diagnosis and genetic counseling are integrative in individualized disease approach.
A randomised, multi-centre trial of total ankle replacement versus ankle arthrodesis in the treatment of patients with end stage ankle osteoarthritis (TARVA): statistical analysis plan
Authors:   on behalf of the TARVA Study Group, Muller Patrick , Skene Simon S. , Chowdhury Kashfia , Cro Suzie , Goldberg Andrew J. , Doré Caroline J.
Published: February 2020

Background

The total ankle replacement versus ankle arthrodesis (TARVA) trial aims to determine which surgical procedure confers the greatest improvement in pain-free function for patients with end-stage ankle osteoarthritis. Both procedures are effective but there has not yet been a direct comparison to establish which is superior. This article describes the statistical analysis plan for this trial as an update to the published protocol. It is written prior to the end of patient follow-up, while the outcome of the trial is still unknown.

Design and methods

TARVA is a randomised, un-blinded, parallel group trial of total ankle replacement versus ankle arthrodesis. The primary outcome is the Manchester-Oxford Foot Questionnaire walking/standing domain score at 52 weeks post-surgery. Secondary outcomes include measures of pain, social interaction, physical function, quality of life, and range of motion. We describe in detail the statistical aspects of TARVA: the outcome measures, the sample size calculation, general analysis principles including treatment of missing data, the planned descriptive statistics and statistical models, and planned subgroup and sensitivity analyses.

Discussion

The TARVA statistical analysis will provide comprehensive and precise information on the relative effectiveness of the two treatments. The plan will be implemented in January 2020 when follow-up for the trial is completed.

Trial registration

ISRCTN registry number 60672307, ClinicalTrials.gov registration number NCT02128555. Registered 1 May 2014. Recruitment started in January 2015 and ended in January 2019.
A randomized controlled trial investigating the effect of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols on the intestinal microbiome and inflammation in patients with ulcerative colitis: study protocol for a randomized controlled trial
Authors: Milajerdi Alireza , Sadeghi Omid , Siadat Seyed Davar , Keshavarz Seyed Ali , Sima Alireza , Vahedi Homayoon , Adibi Peyman , Esmaillzadeh Ahmad
Published: February 2020

Background

No conclusive treatment is available for irritable bowel disease (IBD). Adherence to a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) might alleviate clinical symptoms of IBD. However, no study has investigated the effect of low FODMAPs diet on the intestinal microbiota and inflammatory biomarkers in patients with IBD. The aim of current study is to examine the effect a low FODMAP diet on IBD symptoms, inflammation, and the intestinal microbiota in patients with ulcerative colitis.

Methods and analysis

This study is a randomized clinical trial. Thirty patients with mild to moderate ulcerative colitis will be randomly allocated to receive a low FODMAP diet (n = 15) or to continue their usual diet as control (n = 15), for 4 weeks. The quantity of intestinal microbiota including Clostridium cluster IV, Faecalibacterium prausnitzii, Rosburia spp., Lactobacillus spp., Bifidobacteria spp., Akkermansia muciniphila, Bacteroides fragilis, and Ruminococcus spp., and the Firmicutes to Bacteroidetes ratio and calprotectin and lactoferrin levels will be explored in fecal samples from patients. In addition, anthropometric measures and biochemical assessments including serum concentrations of highly sensitive-C reactive protein (hs-CRP), tumour necrosis factor-α (TNF-α) and IL-1β will be taken from patients at baseline and end of the study. The study has been registered in IRCT (IRCT20181126041763N1; registration date: 2019-01-18).

Discussion

Consumption of a low-FODMAP diet might decrease systemic and intestinal inflammation, change the bacterial population in the gut, and modulate clinical symptoms in patients with ulcerative colitis. Further studies investigating the effect of such a diet on other variables, including other bacterial species and inflammatory cytokines, are required to confirm future findings of this trial.