bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional outcome of total knee replacement: a study protocol for a prospective, double-blinded, parallel-group randomized, clinical controlled trial of novel, personalized and conventional implants
Authors: Irmola T. , Kangas J. , Eskelinen A. , Niemeläinen M. , Huhtala H. , Mattila V. M. , Moilanen T.
Published: October 2019

Background

The development of total knee replacement (TKR) implant designs aims to improve outcome regarding pain, function, joint stiffness, instability, patellar problems, and ultimately wear of the implant. Recently, two major orthopaedic implant manufacturers launched a new generation of TKR implants which, according to the manufacturers, provide improved functional outcome. However, the benefits of these new TKR designs claimed by the manufacturers in terms of improved functional outcome still lack scientific documentation. The present randomized controlled trial has been designed to compare three fixed bearing, cemented cruciate-retaining (CR) designs; one of the new personalized TKR design with two conventional TKR designs with the main emphasis being on functional outcome.

Methods

The present study is a prospective, double-blinded, randomized, single-center intervention trial. A total of 240 patients will be recruited to participate in a parallel-group study at Coxa Hospital for Joint Replacement, Tampere, Finland. We will compare the short-term functional outcome of TKR performed with a novel personalized TKR design (Persona CR, Zimmer, Warsaw, IN, USA) against TKRs performed with two conventional designs (PFC CR, DePuy, Warsaw, IN, USA and Nexgen CR, Zimmer, Warsaw, IN, USA). In total, 80 patients will be randomized in each of the three study arms. The primary outcome in this study is the Oxford Knee Score (OKS), which is a validated patient-reported outcome measure (PROM). Secondary outcome measures include the Forgotten Joint Score, the 15D, the UCLA activity score, and the VAS pain scale. The results will be analyzed after 2-year follow-up.

Discussion

This paper presents a prospective, randomized, single-center trial study protocol. It provides details of patient randomization, PROMs, follow-up, methods of analysis of the material, and publication plan. An important aspect that will be considered in the study will be the economic effects of the novel designs as they are substantially more expensive, and the benefits of the added costs remain unknown. In addition, it is especially important to carry out evaluative studies in independent centers that are not biased by the interests of the manufacturers.

Trial registration

Retrospectively registered, November, 2017,ClinicalTrials.govIdentifier:NCT03339557.
Folate-receptor 1 level in periodontal disease: a pilot study
Authors: Alkan Duygu , Guven Berrak , Turer Cigdem Coskun , Balli Umut , Can Murat
Published: October 2019

Background

The purpose of this study was to investigate gingival crevicular fluid (GCF) and serum folate-receptor 1 (FOLR1) levels in subjects with different periodontal status.

Methods

The study consists of three groups: Healthy group (n = 15), gingivitis group (n = 15) and chronic periodontitis group (n = 15). Clinical periodontal parameters including probing pocket depth (PPD), clinical attachment level (CAL), gingival index (GI) and bleeding on probing (BOP) were assessed. GCF and serum samples were collected from each patient and were analyzed FOLR1 levels by enzyme-linked immunosorbent assay.

Results

The values of FOLR1 in GCF were higher in gingivitis and periodontitis groups than among patient in control group (p < 0.016). Serum FOLR1 levels showed no significant difference between the groups. A significant correlation was observed between FOLR1 levels of GCF and BOP (p < 0.05).

Conclusions

Our preliminary data suggest that FOLR1 is not useful in monitoring the periodontal disease. Further studies are necessary to clarify the role, regulation and function of folate and it’s receptors in the pathogenesis of periodontal disease.
Iranian propolis efficiently inhibits growth of oral streptococci and cancer cell lines
Authors: Asgharpour Fariba , Moghadamnia Ali Akbar , Zabihi Ebrahim , Kazemi Sohrab , Ebrahimzadeh Namvar Amirmorteza , Gholinia Hemmat , Motallebnejad Mina , Nouri Hamid Reza
Published: October 2019

Background

Propolis is a natural bee product with a wide range of biological activities that are related to its chemical composition. The present study investigated the quantification of quercetin (Q) in Ardabil ethanol extract of propolis (AEEP), and then compared its anti-bacterial, anti- biofilm and cytotoxic effects on cancer and normal cell lines.

Method

In the present study, the chemical composition of AEEP was determined through the high-performance liquid chromatography (HPLC). The AEEP and its main component, quercetin (Q), were evaluated in vitro against 57 oral streptococci by a broth micro-dilution method. The biofilm formation was assessed through the crystal violet staining and MTT assays. The impact of AEEP and Q anti-proliferative effect were evaluated on the fibroblast as normal and cancer cell lines (KB and A431).

Results

The Q concentration in the composition of AEEP was 6.9% of all its components. The findings indicated that the AEEP and Q were efficient against the cariogenic bacteria and were able to inhibit the S.mutans biofilm adherence at a sub-MIC concentration. Moreover, electron micrographs indicated the inhibition of biofilms compared to control biofilms. In addition, the AEEP and Q indicated a dose-dependent cytotoxic effect on A431 and KB cell lines. On the contrary, they had no cytotoxic effect on fibroblast cells.

Conclusion

The results indicated that the synergistic impact of main components of AEEP was related to the inhibition of the cancer cell proliferation, cariogenic bacteria and oral biofilm formation. It may play a promising role in the complementary medicine and, it is suggested to be used as food additives.
Medical students’ perception on fecal microbiota transplantation
Authors: Madar Petru C. , Petre Oana , Baban Adriana , Dumitrascu Dan L.
Published: October 2019

Background

Fecal microbiota transplantation (FMT) has become an emergent method in the therapy of several intestinal diseases, mainly in Clostridium difficile recurrence. The training of FMT in medical schools is at its beginning and in countries where FMT is only occasionally carried out, it is important to know the perception of medical students on FMT.

Methods

We undertook a survey of 3rd year medical students not exposed to official academic information on FMT in order to find out their knowledge, beliefs and attitude toward FMT. A number of 80 students were asked to fill a dedicated online questionnaire.

Results

52 out of 80 third year medical students anonymously filled the questionnaire (65% response rate). 34% of respondents reported to have at least a medium level of knowledge regarding FMT. The top indication for FMT identified by 76.9% was C. difficile infection; however, 60% believed FMT to be a promising therapy for a high number of conditions and while almost all respondents (98.1%) would recommend it, 88.4% would explore other options first. Colonoscopy was considered the optimal method of delivery by 42.3%. Only 39% of participants believed that patients would accept FMT, however 71% considered that a more socially acceptable name for the procedure and anonymous donors would increase acceptance rate. The risk of transmitting a disease undetected by donor stool screening procedures to the recipient was the most worrying side effect considered by 75% of respondents. 54% believed that more research is required for FMT to enter clinical practice and 55.7% of respondents would enroll patients in controlled clinical trials.

Conclusions

Medical students not exposed to educational information on FMT seem to be somewhat well informed about this method and would recommend it to their patients. Students, however, need to know more on the indications of FMT.
Regeneration in the ctenophore Mnemiopsis leidyi occurs in the absence of a blastema, requires cell division, and is temporally separable from wound healing
Authors: Ramon-Mateu Julia , Ellison S. Tori , Angelini Thomas E. , Martindale Mark Q.
Published: October 2019

Background

The ability to regenerate is a widely distributed but highly variable trait among metazoans. A variety of modes of regeneration has been described for different organisms; however, many questions regarding the origin and evolution of these strategies remain unanswered. Most species of ctenophore (or “comb jellies”), a clade of marine animals that branch off at the base of the animal tree of life, possess an outstanding capacity to regenerate. However, the cellular and molecular mechanisms underlying this ability are unknown. We have used the ctenophoreMnemiopsis leidyias a system to study wound healing and adult regeneration and provide some first-time insights of the cellular mechanisms involved in the regeneration of one of the most ancient extant group of multicellular animals.

Results

We show that cell proliferation is activated at the wound site and is indispensable for whole-body regeneration. Wound healing occurs normally in the absence of cell proliferation forming a scar-less wound epithelium. No blastema-like structure is generated at the cut site, and pulse-chase experiments and surgical intervention show that cells originating in the main regions of cell proliferation (the tentacle bulbs) do not seem to contribute to the formation of new structures after surgical challenge, suggesting a local source of cells during regeneration. While exposure to cell-proliferation blocking treatment inhibits regeneration, the ability to regenerate is recovered when the treatment ends (days after the original cut), suggesting that ctenophore regenerative capabilities are constantly ready to be triggered and they are somehow separable of the wound healing process.

Conclusions

Ctenophore regeneration takes place through a process of cell proliferation-dependent non-blastemal-like regeneration and is temporally separable of the wound healing process. We propose that undifferentiated cells assume the correct location of missing structures and differentiate in place. The remarkable ability to replace missing tissue, the many favorable experimental features (e.g., optical clarity, high fecundity, rapid regenerative performance, stereotyped cell lineage, sequenced genome), and the early branching phylogenetic position in the animal tree, all point to the emergence of ctenophores as a new model system to study the evolution of animal regeneration.
Identification of 3 subpopulations of tumor-infiltrating immune cells for malignant transformation of low-grade glioma
Authors: Lu Jiacheng , Li Hailin , Chen Zhengxin , Fan Ligang , Feng Shuang , Cai Xiaomin , Wang Huibo
Published: October 2019

Background

Tumor-infiltrating immune cells (TIICs) are highly relevant to clinical outcome of glioma. However, previous studies cannot account for the diverse functions that make up the immune response in malignant transformation (MT) from low-grade glioma (LGG) to high-grade glioma (HGG).

Methods

Transcriptome level, genomic profiles and its relationship with clinical practice were obtained from TCGA and CGGA database. The “Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT)” algorithm was used to estimate the fraction of 22 immune cell types. We divided the TCGA and CGGA set into an experiment set (n = 174) and a validation set (n = 74) by random number table method. Univariate and multivariate analyses were performed to evaluate the 22 TIICs’ value for MT in LGG. ROC curve was plotted to calculate area under curve (AUC) and cut-off value.

Results

Heterogeneity between TIICs exists in both intra- and inter-groups. Several TIICs are notably associated with tumor grade, molecular subtypes and survival. T follicular helper (TFH) cells, activated NK Cells and M0 macrophages were screened out to be independent predictors for MT in LGG and formed an immune risk score (IRS) (AUC = 0.732, p < 0.001, 95% CI 0.657–0.808 cut-off value = 0.191). In addition, the IRS model was validated by validation group, Immunohistochemistry (IHC) and functional enrichment analyses.

Conclusions

The proposed IRS model provides promising novel signatures for predicting MT from LGG to HGG and may bring a better design of glioma immunotherapy studies in years to come.
18F-labeled magnetic nanoparticles for monitoring anti-angiogenic therapeutic effects in breast cancer xenografts
Authors: Wang Yanshu , Liu Huanhuan , Yao Defan , Li Jinning , Yang Shuyan , Zhang Caiyuan , Chen Weibo , Wang Dengbin
Published: October 2019

Purpose

To develop a novel fluorine-18 (18F)-labeled arginine–glycine–aspartic acid (RGD)-coupled ultra-small iron oxide nanoparticle (USPIO) (hereafter, referred to as 18F-RGD@USPIO) and conduct an in-depth investigation to monitor the anti-angiogenic therapeutic effects by using a novel dual-modality PET/MRI probe.

Methods

The RGD peptide and 18F were coupled onto USPIO by click chemistry. In vitro experiments including determination of stability, cytotoxicity, cell binding of the obtained 18F-RGD@USPIO were carried out, and the targeting kinetics and bio-distribution were tested on an MDA-MB-231 tumor model. A total of 20 (n = 10 per group) MDA-MB-231 xenograft-bearing mice were treated with bevacizumab or placebo (intraperitoneal injections of bevacizumab or a volume-equivalent placebo solution at the dose of 5 mg/kg for consecutive 7 days, respectively), and underwent PET/CT and MRI examinations with 18F-RGD@USPIO before and after treatment. Imaging findings were validated by histological analysis with regard to β3-integrin expression (CD61 expression), microvascular density (CD31 expression), and proliferation (Ki-67 expression).

Results

Excellent stability, low toxicity, and good specificity to endothelial of 18F-RGD@USPIO were confirmed. The best time point for MRI scan was 6 h post-injection. No intergroup differences were observed in tumor volume development between baseline and day 7. However, 18F-RGD@USPIO binding was significantly reduced after bevacizumab treatment compared with placebo, both on MRI (P < 0.001) and PET/CT (P = 0.002). Significantly lower microvascular density, tumor cell proliferation, and integrin β3 expression were noted in the bevacizumab therapy group than the placebo group, which were consistent with the imaging results.

Conclusion

PET/MRI with the dual-modality nanoprobe, 18F-RGD@USPIO, can be implemented as a noninvasive approach to monitor the therapeutic effects of anti-angiogenesis in breast cancer model in vivo.
Health-related quality of life outcomes in pediatric patients with cardiac rhythm devices: a cross-sectional study with case-control comparison
Authors: Werner Helene , Lehmann Phaedra , Rüegg Alina , Hilfiker Silvia , Steinmann Karin , Balmer Christian
Published: October 2019

Background

Little is known about health-related quality of life (HRQoL) in pediatric patients with cardiac rhythm devices. This study aims to compare self- and proxy-reported HRQoL in patients with pacemaker (PM) and implantable cardioverter-defibrillator (ICD) to that in sex- and age-matched healthy controls and to examine predictors for generic and disease-specific HRQoL.

Methods

The study included 72 PM and ICD patients (39% females) and 72 sex- and age-matched healthy controls from 3 to 18 years of age. HRQoL data was obtained by the PedsQL 4.0 Generic Core Scales and Pediatric Cardiac Quality of Life Inventory. Medical data was collected retrospectively from medical records.

Results

Patients had significantly lower self- and proxy-reported generic overall HRQoL and lower physical health than healthy controls, and ICD patients also had lower psychosocial health. On multivariate analyses, generic overall HRQoL and physical health was significantly predicted by current cardiac medication (β = −.39,p = .02 for overall HRQoL, respectivelyβ = −.44,p = .006 for physical health). Disease-specific overall HRQoL was only marginally predicted by child age, device type, and the presence of a structural congenital heart disease (p < .10).

Conclusions

This study shows that PM and ICD patients have lower HRQoL than healthy controls and that patients who need cardiac medication are seen by their parents at great risk for lower generic overall HRQoL. Our study also indicates a trend towards higher risk for low disease-specific HRQoL in younger patients, ICD patients, and patients with a structural congenital heart disease. Special attention should be given to these patients as they may benefit from a timely clinical evaluation in order to provide supportive interventions.
Mapping from spatial meaning: bridging Hñahñu (Otomi) ecological knowledge and geo-information tools
Authors: León Villalobos José María , Vázquez García Verónica , Ojeda Trejo Enrique , McCall Michael K. , Hernández Hernández Juan , Sinha Gaurav
Published: October 2019

Background

Hñahñu (Otomi) farmers organize their experiences and ecological learning into a farmland system designed to grow food in areas of scarce water and low soil fertility. The purpose of this paper is to examine Hñahñu concepts and categories pertaining to the farming landscape and the ecological foundations underlying the system, its management implications, and categorial organization in Huitexcalco de Morelos, Mezquital Valley, Mexico.

Methods

Native terms and their links to landscape were recorded and discussed in various workshops. Open interviews and field trips with local experts were used to explain soil and water management practices that allow Hñahñu farmers to maintain sustained yields throughout the year. We then used participatory mapping in order to explore the semantic relations of the terms with the space and its validity in the productive landscape.

Results

We elicited 7 Hñahñu language terms related to landforms, 4 related to land use categories, and 17 related to their constituent components organized in two hierarchical levels. We found thatmotheas a term of land usage was followed bymothee,ñut’athee,gadñhe, ormuiñhe; these primarily refer to the topographic position of the parcel and the form of access to water for irrigation. Stone barriers and earth channels represent the functional structures that are most commonly used by Hñahñu farmers to retain soil and water. In the participatory mapping results,mothe muiñhedisplayed a robust spatial link with the gullies. Identifying other landscape categories required a substantial understanding both of management practices of soil and water and forms of organization.

Conclusions

This study revealed a complex system of knowledge that contributes to the continued proper management of the local landscape. The terms and their elicited meanings are key to understand the ways in which Hñahñu farmers conceptualize and relate the reality of their landscape and its cultural meanings. Scale and perception were found to have a determining role in defining their taxonomic organization, semantic structure, and relations in space.
IMP-ICDX: an injury mortality prediction based on ICD-10-CM codes
Authors: Wang Muding , Qiu Wusi , Zeng Yunji , Fan Wenhui , Lian Xiao , Shen Yi
Published: October 2019

Background

The International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) Injury Severity Score (ICISS) is a risk adjustment model when injuries are recorded using ICD-9-CM coding. The trauma mortality prediction model (TMPM-ICD9) provides better calibration and discrimination compared with ICISS and injury severity score (ISS). Though TMPM-ICD9 is statistically rigorous, it is not precise enough mathematically and has the tendency to overestimate injury severity. The purpose of this study is to develop a new ICD-10-CM injury model which estimates injury severities for every injury in the ICD-10-CM lexicon by a combination of rigorous statistical probit models and mathematical properties and improves the prediction accuracy.

Methods

We developed an injury mortality prediction (IMP-ICDX) using data of 794,098 patients admitted to 738 hospitals in the National Trauma Data Bank from 2015 to 2016. Empiric measures of severity for each of the trauma ICD-10-CM codes were estimated using a weighted median death probability (WMDP) measurement and then used as the basis for IMP-ICDX. ISS (version 2005) and the single worst injury (SWI) model were re-estimated. The performance of each of these models was compared by using the area under the receiver operating characteristic (AUC), the Hosmer-Lemeshow (HL) statistic, and the Akaike information criterion statistic.

Results

IMP-ICDX exhibits significantly better discrimination (AUCIMP-ICDX, 0.893, and 95% confidence interval (CI), 0.887 to 0.898; AUCISS, 0.853, and 95% CI, 0.846 to 0.860; and AUCSWI, 0.886, and 95% CI, 0.881 to 0.892) and calibration (HLIMP-ICDX, 68, and 95% CI, 36 to 98; HLISS, 252, and 95% CI, 191 to 310; and HLSWI, 92, and 95% CI, 53 to 128) compared with ISS and SWI. All models were improved after the extension of age, gender, and injury mechanism, but the augmented IMP-ICDX still dominated ISS and SWI by every performance.

Conclusions

The IMP-ICDX has a better discrimination and calibration compared to ISS. Therefore, we believe that IMP-ICDX could be a new viable trauma research assessment method.
Outcomes of internal fixation versus hemiarthroplasty for elderly patients with an undisplaced femoral neck fracture: a systematic review and meta-analysis
Authors: Ma Hsuan-Hsiao , Chou Te-Feng Arthur , Tsai Shang-Wen , Chen Cheng-Fong , Wu Po-Kuei , Chen Wei-Ming
Published: October 2019

Background

Although internal fixation has been the main treatment option for elderly patients with an undisplaced femoral neck fracture, it is associated with a high reoperation rate. Some surgeons have discussed the use of hemiarthroplasty, but there is limited literature comparing these two treatment modalities. In this study, we compared the perioperative results of hemiarthroplasty with internal fixation for undisplaced femoral neck fractures.

Methods

We performed a comprehensive review of literatures on PubMed, Web of Science, Embase, and the Cochrane Library for randomized controlled trials and comparative observational studies. Of the 441 studies initially identified, 3 met all inclusion criteria. Two reviewers independently graded study quality and abstracted relevant data including reoperation rate, mortality rate, Harris Hip Score (HHS), length of hospital stay, and operation duration.

Results

Our results revealed that hemiarthroplasty was associated with a lower reoperation rate than the internal fixation group (OR 4.489; 95% CI 2.030 to 9.927). Mortality rate at postoperative 1 month and 1 year and HHS at postoperative 1 year and 2 years were not different. Length of hospital stay (SMD − 0.800, 95% CI − 1.011 to − 0.589) and operation duration (SMD − 2.497, 95% CI − 2.801 to − 2.193) were shorter in the internal fixation group.

Conclusions

Compared with the internal fixation group, patients that underwent hemiarthroplasty had a lower reoperation rate and an equivalent overall mortality rate. Our meta-analysis suggests that hemiarthroplasty might be a better treatment choice than internal fixation in treating elderly patients with an undisplaced femoral neck fracture.
The use of a machine-learning algorithm that predicts hypotension during surgery in combination with personalized treatment guidance: study protocol for a randomized clinical trial
Authors: Wijnberge M. , Schenk J. , Terwindt L. E. , Mulder M. P. , Hollmann M. W. , Vlaar A. P. , Veelo D. P. , Geerts B. F.
Published: October 2019

Background

Intraoperative hypotension is associated with increased morbidity and mortality. Current treatment is mostly reactive. The Hypotension Prediction Index (HPI) algorithm is able to predict hypotension minutes before the blood pressure actually decreases. Internal and external validation of this algorithm has shown good sensitivity and specificity. We hypothesize that the use of this algorithm in combination with a personalized treatment protocol will reduce the time weighted average (TWA) in hypotension during surgery spent in hypotension intraoperatively.

Methods/design

We aim to include 100 adult patients undergoing non-cardiac surgery with an anticipated duration of more than 2 h, necessitating the use of an arterial line, and an intraoperatively targeted mean arterial pressure (MAP) of > 65 mmHg. This study is divided into two parts; in phase A baseline TWA data from 40 patients will be collected prospectively. A device (HemoSphere) with HPI software will be connected but fully covered. Phase B is designed as a single-center, randomized controlled trial were 60 patients will be randomized with computer-generated blocks of four, six or eight, with an allocation ratio of 1:1. In the intervention arm the HemoSphere with HPI will be used to guide treatment; in the control arm the HemoSphere with HPI software will be connected but fully covered. The primary outcome is the TWA in hypotension during surgery.

Discussion

The aim of this trial is to explore whether the use of a machine-learning algorithm intraoperatively can result in less hypotension. To test this, the treating anesthesiologist will need to change treatment behavior from reactive to proactive.

Trial registration

This trial has been registered with the NIH, U.S. National Library of Medicine at ClinicalTrials.gov, ID: NCT03376347. The trial was submitted on 4 November 2017 and accepted for registration on 18 December 2017.
Comparison of the effect of three different protein content enteral diets on serum levels of proteins, nitrogen balance, and energy expenditure in critically ill infants: study protocol for a randomized controlled trial
Authors: Fernández Reyes , Urbano Javier , Carrillo Ángel , Vivanco Ana , Solana María José , Rey Corsino , López-Herce Jesús
Published: October 2019

Background

Nutritional support is essential in the care of critically ill children since malnutrition in this population is associated with increased morbidity and mortality. Injury in patients admitted to pediatric intensive care units (PICU) results in a catabolic state and augmented protein breakdown, leading to a negative protein balance. Current recommendations about protein prescription in the PICU are fundamentally based on expert opinions, and the minimum threshold is 1.5 g/kg per day of protein, although protein needs could be higher in certain subgroups of patients. The main objectives of the present study are to examine whether the administration of a protein-enriched infant formula increases the serum levels of total proteins, albumin, prealbumin, transferrin, and retinol and improves nitrogen balance and to analyze the effect of the high-protein diet on energy expenditure. A secondary objective is to register possible secondary effects of the protein-enriched diet.

Methods

A multicenter prospective randomized controlled trial (RCT) will be performed in three hospitals. Patients meeting inclusion criteria will be randomly allocated to one of three enteral feeding formulae with different protein contents. Blood and urine test, nitrogen balance assessment, and energy expenditure testing by indirect calorimetry will be performed at the beginning of the nutrition regimen and at 24 h, 72 h and 5–7 days after initiation. The sample size for this trial is estimated to be 90 participants (about 30 participants in each group). The data analysis will be by intention to treat.

Discussion

This RCT will provide new data about the amount of protein needed to improve levels of serum protein and nitrogen balance, a surrogate of protein balance, in critically ill infants receiving enteral nutrition.

Trial registration

ClinicalTrials.gov identifier: NCT03901742. Registered April 1, 2019 – Retrospectively registered.
The Salt Swap intervention to reduce salt intake in people with high blood pressure: protocol for a feasibility randomised controlled trial
Authors: Payne Riches Sarah , Piernas Carmen , Aveyard Paul , Sheppard James P. , Rayner Mike , Jebb Susan A.
Published: October 2019

Background

High salt intake is a risk factor for hypertension and cardiovascular disease. Reducing salt intake has been shown to reduce blood pressure. Despite population-level interventions, including product reformulation and public awareness campaigns, adult salt consumption in the UK still exceeds recommendations; this is primarily due to salt consumed in processed and pre-packaged foods. Moderate or high-intensity dietary advice to encourage individuals to reduce their salt intake has been shown to be effective at reducing blood pressure, but evidence of the effectiveness of interventions that are suitable for delivery at scale in routine primary care is scarce. This feasibility trial investigates a complex behavioural change intervention to reduce dietary salt intake and blood pressure by encouraging individuals to purchase lower-salt foods when grocery shopping.

Methods

This randomised controlled trial will test the feasibility of a novel intervention to reduce salt intake, and the trial procedures to assess its effectiveness. We will recruit participants through UK general practices and randomise 40 participants with high blood pressure, in a 2:1 allocation to receive either the Salt Swap intervention or a control information leaflet. The primary outcomes relate to the criteria for progression to a large-scale trial. These include follow-up rates at 6 weeks, fidelity of intervention delivery and use of the intervention mobile app. Secondary outcomes include the effect of the intervention on the salt content of purchased foods (grams per 100 g), urinary sodium excretion assessed through 24-hour urine samples and blood pressure. Trial process measures will be collected and qualitative assessment will provide insights into participant engagement with the intervention content and perceived barriers to and facilitators of salt reduction dietary behavioural change.

Discussion

If the outcomes indicate the trial is feasible and there is evidence that behavioural change may result in salt reduction, we will proceed to a definitive trial to test the effectiveness of the intervention to lower blood pressure. If successful, this intervention approach could be applied not only to people with high blood pressure, but also to the wider population with normal blood pressure in whom dietary salt intake exceeds recommendations.

Trial registration

ISRCTN, 20910962. Registered on 5 April 2017.
Variable levels of drift in tunicate cardiopharyngeal gene regulatory elements
Authors: Colgan William , Leanza Alexis , Hwang Ariel , DeBiasse Melissa B. , Llosa Isabel , Rodrigues Daniel , Adhikari Hriju , Barreto Corona Guillermo , Bock Saskia , Carillo-Perez Amanda , Currie Meagan , Darkoa-Larbi Simone , Dellal Daniel , Gutow Hanna , Hokama Pascha , Kibby Emily , Linhart Noah , Moody Sophia , Naganuma Allison , Nguyen Diep , Stanton Ryan , Stark Sierra , Tumey Cameron , Velleca Anthony , Ryan Joseph F. , Davidson Brad
Published: October 2019

Background

Mutations in gene regulatory networks often lead to genetic divergence without impacting gene expression or developmental patterning. The rules governing this process of developmental systems drift, including the variable impact of selective constraints on different nodes in a gene regulatory network, remain poorly delineated.

Results

Here we examine developmental systems drift within the cardiopharyngeal gene regulatory networks of two tunicate species,Corella inflataandCiona robusta.Cross-species analysis of regulatory elements suggests thattrans-regulatory architecture is largely conserved between these highly divergent species. In contrast,cis-regulatory elements within this network exhibit distinct levels of conservation. In particular, while most of the regulatory elements we analyzed showed extensive rearrangements of functional binding sites, the enhancer for the cardiopharyngeal transcription factorFoxFis remarkably well-conserved. Even minor alterations in spacing between binding sites lead to loss ofFoxFenhancer function, suggesting that boundtrans-factors form position-dependent complexes.

Conclusions

Our findings reveal heterogeneous levels of divergence across cardiopharyngealcis-regulatory elements. These distinct levels of divergence presumably reflect constraints that are not clearly associated with gene function or position within the regulatory network. Thus, levels ofcis-regulatory divergence or drift appear to be governed by distinct structural constraints that will be difficult to predict based on network architecture.
Development of a simple and high-yielding fed-batch process for the production of porcine circovirus type 2 virus-like particle subunit vaccine
Authors: Cao Wenlong , Cao Hui , Yi Xiaoping , Zhuang Yingping
Published: October 2019

The cap protein is encoded by the orf2 gene of porcine circovirus type 2 (PCV2) has the main antigen epitope of PCV2 and can form virus-like particles (VLPs), which are expressed in insect cells. PCV2-VLPs can effectively inhibit PCV2 replication as a subunit vaccine. In this study, a robust and reliable fed-batch process was successfully developed for the production of PCV2-VLPs by Sf9 cells. The feeding solution, feeding strategy, and cell density at infection were optimized to maximize the final PCV2-VLPs production yields. The cell density at infection and the volumetric PCV2-VLPs production reached 12 × 106 cells/mL and 110 mg/L, respectively, which yielded 3- and 3.6-fold enhancements compared to the batch culture. The PCV2-VLPs produced in fed-batch culture were not different from the PCV2-VLPs produced in a batch culture in an immunity test. A highly efficient production process was produced for PCV2-VLPs subunit vaccines, which could provide an effective means for the industrial production of PCV2 vaccines.
Evaluation of least significant changes of pulse contour analysis-derived parameters
Authors: de Courson Hugues , Ferrer Loic , Cane Grégoire , Verchère Eric , Sesay Musa , Nouette-Gaulain Karine , Biais Matthieu
Published: October 2019

Background

Many maneuvers assessing fluid responsiveness (minifluid challenge, lung recruitment maneuver, end-expiratory occlusion test, passive leg raising) are considered as positive when small variations in cardiac index, stroke volume index, stroke volume variation or pulse pressure variation occur. Pulse contour analysis allows continuous and real-time cardiac index, stroke volume, stroke volume variation and pulse pressure variation estimations. To use these maneuvers with pulse contour analysis, the knowledge of the minimal change that needs to be measured by a device to recognize a real change (least significant change) has to be studied. The aim of this study was to evaluate the least significant change of cardiac index, stroke volume index, stroke volume variation and pulse pressure variation obtained using pulse contour analysis (ProAQT®, Pulsion Medical System, Germany).

Methods

In this observational study, we included 50 mechanically ventilated patients undergoing neurosurgery in the operating room. Cardiac index, stroke volume index, pulse pressure variation and stroke volume variation obtained using ProAQT® (Pulsion Medical System, Germany) were recorded every 12 s during 15-min steady-state periods. Least significant changes were calculated every minute.

Results

Least significant changes statistically differed over time for cardiac index, stroke volume index, pulse pressure variation and stroke volume variation (p < 0.001). Least significant changes ranged from 1.3 to 0.7% for cardiac index, from 1.3 to 0.8% for stroke volume index, from 10 to 4.9% for pulse pressure variation and from 10.8 to 4.3% for stroke volume variation.

Conclusion

To conclude, the present study suggests that pulse contour analysis is able to detect rapid and small changes in cardiac index and stroke volume index, but the interpretation of rapid and small changes of pulse pressure variation and stroke volume variation must be done with caution.
Modeling the spread of porcine reproductive and respiratory syndrome virus (PRRSV) in a swine population: transmission dynamics, immunity information, and optimal control strategies
Authors: Phoo-ngurn Phithakdet , Kiataramkul Chanakarn , Chamchod Farida
Published: October 2019

Porcine reproductive and respiratory syndrome (PRRS) is an important swine disease that affects many swine industries worldwide. The disease can cause reproductive failure and respiratory problems in a swine population. As vaccination is an important tool to control the spread of PRRS virus (PRRSV), we employ a mathematical model to investigate the transmission dynamics of PRRSV and the effects of immunity information, as well as vaccination control strategies. We also explore optimal vaccination coverage and vaccination rate to minimize the number of infected swines and vaccination efforts. Our results suggest that: (i) higher vaccination coverage and vaccination rate together with prior knowledge about immunity may help reduce the prevalence of PRRSV, and (ii) longer maximum vaccination efforts are required when swines stay longer in a population and it takes them longer time to recover from PRRS infections.
Before Consent: Qualitative Analysis of Deliberations of Patients With Advanced Cancer About Early-Phase Clinical Trials
Authors: Garrett Sarah B. , Matthews Thea M. , Abramson Corey M. , Koenig Christopher J. , Hlubocky Fay J. , Daugherty Christopher K. , Munster Pamela N. , Dohan Daniel
Published: October 2019

PURPOSE:

Patients with advanced cancer and oncologists deliberate about early-phase (EP) trials as they consider whether to pursue EP trial enrollment. We have limited information about those deliberations and how they may facilitate or impede trial initiation. This study describes these deliberations and their relationship to trial initiation.

PATIENTS AND METHODS:

We collected longitudinal, ethnographic data on deliberations of patients with advanced cancer at two academic medical centers. We used constant comparative and framework analyses to characterize the deliberative process and its relationship to trial initiation.

RESULTS:

Of 96 patients with advanced cancer, 26% initiated EP enrollment and 19% joined a trial. Constant comparative analysis revealed two foci of deliberation. Setting the stage focused on patient and physician support for EP trial involvement, including patients’ interest in research and oncologists’ awareness of trials and assessment of patient fit. Securing a seat focused on eligibility for and entrance to a specific trial and involved trial availability, treatment history, disease progression, and enrollment timing. Patients enrolled in a trial only when both stages could be successfully navigated.

CONCLUSION:

Ethnographic data revealed two foci of deliberation about EP trial enrollment among patients with advanced cancer. Physician support played a consequential role in both stages, but enrollment also reflected factors beyond the control of any specific individual. Insights from this study, combined with other recent studies of trial enrollment, advance our understanding of the complex process of EP trial accrual and may help identify strategies to improve rates of participation.
Development, Reporting, and Evaluation of Clinical Practice Guidelines
Authors: Benzon Honorio T. , Joshi Girish P. , Gan Tong J. , Vetter Thomas R.
Published: October 2019

Clinical practice parameters have been published with greater frequency by professional societies and groups of experts. These publications run the gamut of practice standards, practice guidelines, consensus statements or practice advisories, position statements, and practice alerts. The definitions of these terms have been clarified in an accompanying article. In this article, we present the criteria for high-quality clinical practice parameters and outline a process for developing them, specifically the Delphi method, which is increasingly being used to build consensus among content experts and stakeholders. Several tools for grading the level of evidence and strength of recommendation are offered and compared. The speciousness of categorizing guidelines as evidence-based or consensus-based will be explained. We examine the recommended checklist for reporting and appraise the tools for evaluating a practice guideline. This article is geared toward developers and reviewers of clinical practice guidelines and consensus statements.
Molecular and mechanical signals determine morphogenesis of the cerebral hemispheres in the chicken embryo
Authors: Garcia Kara E. , Stewart Wade G. , Espinosa M. Gabriela , Gleghorn Jason P. , Taber Larry A.
Published: October 2019

During embryonic development, the telecephalon undergoes extensive growth and cleaves into right and left cerebral hemispheres. Although molecular signals have been implicated in this process and linked to congenital abnormalities, few studies have examined the role of mechanical forces. In this study, we quantified morphology, cell proliferation and tissue growth in the forebrain of chicken embryos during Hamburger-Hamilton stages 17-21. By altering embryonic cerebrospinal fluid pressure during development, we found that neuroepithelial growth depends on not only chemical morphogen gradients but also mechanical feedback. Using these data, as well as published information on morphogen activity, we developed a chemomechanical growth law to mathematically describe growth of the neuroepithelium. Finally, we constructed a three-dimensional computational model based on these laws, with all parameters based on experimental data. The resulting model predicts forebrain shapes consistent with observations in normal embryos, as well as observations under chemical or mechanical perturbation. These results suggest that molecular and mechanical signals play important roles in early forebrain morphogenesis and may contribute to the development of congenital malformations.
Exercise Thermoregulation with a Simulated Burn Injury: Impact of Air Temperature
Authors: CRAMER MATTHEW N. , MORALEZ GILBERT , HUANG MU , KOUDA KEN , POH PAULA Y. S. , CRANDALL CRAIG G.
Published: October 2019

The U.S. Army’s Standards of Medical Fitness (AR 40-501) states: “Prior burn injury (to include donor sites) involving a total body surface area of 40% or more does not meet the standard.” However, the standard does not account for the interactive effect of burn injury size and air temperature on exercise thermoregulation.

Purpose

To evaluate whether the detrimental effect of a simulated burn injury on exercise thermoregulation is dependent on air temperature.

Methods

On eight occasions, nine males cycled for 60 min at a fixed metabolic heat production (6 W·kg−1) in air temperatures of 40°C or 25°C with simulated burn injuries of 0% (Control), 20%, 40%, or 60% of total body surface area (TBSA). Burn injuries were simulated by covering the skin with an absorbent, vapor-impermeable material to impede evaporation from the covered areas. Core temperature was measured in the gastrointestinal tract via telemetric pill.

Results

In 40°C conditions, greater elevations in core temperature were observed with 40% and 60% TBSA simulated burn injuries versus Control (P < 0.01). However, at 25°C, core temperature responses were not different versus Control with 20%, 40%, and 60% TBSA simulated injuries (P = 0.97). The elevation in core temperature at the end of exercise was greater in the 40°C environment with 20%, 40%, and 60% TBSA simulated burn injuries (P ≤ 0.04).

Conclusions

Simulated burn injuries ≥20% TBSA exacerbate core temperature responses in hot, but not temperate, air temperatures. These findings suggest that the U.S. Army’s standard for inclusion of burned soldiers is appropriate for hot conditions, but could lead to the needless discharge of soldiers who could safely perform their duties in cooler training/operational settings.
Performance of Principles of the Individual Project by Senior High School Students: Normative and Organizational Aspects
Authors: Петунин О. , Petunin O.
Published: October 2019

The article discusses the regulatory and organizational aspects of the implementation of individual project by senior high school students. This type of activity, according to the federal state educational standard of secondary general education, is mandatory for students in grades 10-11. The goal of an individual project in the form of educational, research and project activities is the improvement of the ULA and the achievement of metasubjective educational results by high school students. At the level of general secondary education, the formation of a project, the methods and methods of its implementation by the senior pupils is possible. In the curriculum should be provided for the implementation of the individual project students. It is carried out by students for one year or two years as part of the study time specifi cally set aside by the curriculum in the part formed by the participants in educational relations. An individual project can serve as an addition to the curriculum of a particular profile.
Artistic and Tectonic Mechanism the Profile-Oriented Environment of Students Visual Culture Development
Authors: Ротмирова Елена , Rotmirova Elena
Published: October 2019

In the modern system of art education, which actualizes the tasks of specialized training of students, the requirements for fi nding local subject methods and means of its diff erentiation and substantive-technological deepening, praxiocentricity and productivity, culture-building and projectivity are being strengthened. Therefore, this article is devoted to the disclosure of the problem of the activation of functional resources of a profi le-oriented artistic and creative environment in situations of constructive stability and success, cultural action. Thus, we propose to consider the artistic-tectonic environmental mechanism of triggering artistic-didactic and visual processes that guarantee the development of the students’ visual culture, but in the direction of creative knowledge and cultural creation for the present and future. Art tectonics is designed to promote both structural and functional environmental sustainability, as well as a deeper meaningfulness of the profi le-oriented actions of its subjects, emphasis on achieving the integrity of pictorial steps, pondering of composite images and symbols, semantic representations.
"O QUE É ISSO CRESCENDO NO MEU BARCO? ”: UM PROJETO DE DIVULGAÇÃO E EXTENSÃO CIENTÍFICA PARA O ENSINO DE BIOLOGIA MARINHA
Authors: Fortunato Humberto Freitas de Medeiros , Vançato Yollanda Carolina Da Silva Ferreira
Published: October 2019

Um projeto de Extensão Universitária foi desenvolvido no ano de 2018 com o objetivo de fornecer conhecimento teórico e prático sobre assuntos relacionados à Biologia Marinha. Oito alunos adolescentes da turma de vela Básico Dingue 2 da ONG Projeto Grael, em Jurujuba, Niterói - Rio de Janeiro participaram das atividades teórico-práticas do projeto. Os alunos mostraram seu conhecimento prévio acerca do assunto, desenvolveram um experimento científico de bioincrustação in situ e produziram cartazes para demonstrar o conhecimento adquirido. De forma geral, o projeto foi executado com sucesso, pois teve um retorno positivo do público-alvo. Este projeto pode ser repetido com diferentes públicos e assim esperamos minimizar o distanciamento entre sociedade e Universidade, atingindo principalmente atuais e futuros profissionais do mar, através da troca de conhecimento teórico e prático sobre Biologia Marinha.