bluuebunny/crossref_metadata_2025 huggingface dataset:
Impacts of foodborne inorganic nanoparticles on the gut microbiota-immune axis: potential consequences for host health
Authors: Lamas Bruno , Martins Breyner Natalia , Houdeau Eric
Published: June 2020

Background

In food toxicology, there is growing interest in studying the impacts of foodborne nanoparticles (NPs, originating from food additives, food supplements or food packaging) on the intestinal microbiome due to the important and complex physiological roles of these microbial communities in host health. Biocidal activities, as described over recent years for most inorganic and metal NPs, could favour chronic changes in the composition and/or metabolic activities of commensal bacteria (namely, intestinal dysbiosis) with consequences on immune functions. Reciprocally, direct interactions of NPs with the immune system (e.g., inflammatory responses, adjuvant or immunosuppressive properties) may in turn have effects on the gut microbiota. Many chronic diseases in humans are associated with alterations along the microbiota-immune system axis, such as inflammatory bowel diseases (IBD) (Crohn’s disease and ulcerative colitis), metabolic disorders (e.g., obesity) or colorectal cancer (CRC). This raises the question of whether chronic dietary exposure to inorganic NPs may be viewed as a risk factor facilitating disease onset and/or progression. Deciphering the variety of effects along the microbiota-immune axis may aid the understanding of how daily exposure to inorganic NPs through various foodstuffs may potentially disturb the intricate dialogue between gut commensals and immunity, hence increasing the vulnerability of the host. In animal studies, dose levels and durations of oral treatment are key factors for mimicking exposure conditions to which humans are or may be exposed through the diet on a daily basis, and are needed for hazard identification and risk assessment of foodborne NPs. This review summarizes relevant studies to support the development of predictive toxicological models that account for the gut microbiota-immune axis.

Conclusions

The literature indicates that, in addition to evoking immune dysfunctions in the gut, inorganic NPs exhibit a moderate to extensive impact on intestinal microbiota composition and activity, highlighting a recurrent signature that favours colonization of the intestine by pathobionts at the expense of beneficial bacterial strains, as observed in IBD, CRC and obesity. Considering the long-term exposure via food, the effects of NPs on the gut microbiome should be considered in human health risk assessment, especially when a nanomaterial exhibits antimicrobial properties.
Aggressive behavior and metacognitive functions: a longitudinal study on patients with mental disorders
Authors: Candini Valentina , Ghisi Marta , Bianconi Giorgio , Bulgari Viola , Carcione Antonino , Cavalera Cesare , Conte Giovanni , Cricelli Marta , Ferla Maria Teresa , Ferrari Clarissa , Iozzino Laura , Macis Ambra , Nicolò Giuseppe , Stefana Alberto , de Girolamo Giovanni ,   for the VIORMED-2 Group, Barlati Stefano , Martinazzoli Assunta , Mina Giuliana , Paleari Roberta , Restaino Francesco , Travasso Bruno , Vita Antonio
Published: June 2020

Background

Metacognitive functions play a key role in understanding which psychological variables underlying the personality might lead a person with a severe mental disorder to commit violent acts against others. The aims of this study were to: (a) investigate the differences between patients with poor metacognitive functioning (PM group) and patients with good metacognitive functioning (GM group) in relation to a history of violence; (b) investigate the differences between the two groups in relation to aggressive behavior during a 1-year follow-up; and (c) analyze the predictors of aggressive behavior.

Methods

In a prospective cohort study, patients with severe mental disorders with and without a lifetime history of serious violence were assessed with a large set of standardized instruments and were evaluated bi-monthly with MOAS in order to monitor any aggressive behavior. The total sample included 180 patients: 56% outpatients and 44% inpatients, and the majority were male (75%) with a mean age of 44 (± 9.8) years, and half of them had a history of violence. The sample was split into two groups: poor metacognition (PM) group and good metacognition (GM) group, according to MAI evaluation scores.

Results

The PM patients reported a history of violence more frequently than GM patients, during the 1-year follow-up, but no differences between groups in aggressive and violent behavior were found. The strongest predictors of aggressive behavior were: borderline and passive–aggressive personality traits and a history of violence, anger, and hostility. The metacognitive functions alone did not predict aggressive behavior, but metacognitive functions interacted with hostility and angry reactions in predicting aggressive behavior.

Conclusions

This study led to some important conclusions: (a) some aspects closely related to violence are predictive of aggressive behavior only in patients with poor metacognition, thus good metacognition is a protective factor; (b) poor metacognition is associated with a history of violence, which in turn increases the risk of committing aggressive behavior.
Vitamin D deficiency mediates the relationship between dietary patterns and depression: a case–control study
Authors: Sotoudeh Gity , Raisi Firoozeh , Amini Maryam , Majdzadeh Reza , Hosseinzadeh Mahdieh , Khorram Rouz Fatemeh , Khosravi Maryam
Published: June 2020

Background

Depression is a major contributor to disability-adjusted life years (DALY) lost in the world. Dietary patterns are widely used to investigate diet–disease relations. In the current study, the relationship between dietary patterns and depression was investigated. Besides, the role of serum vitamin D, zinc, magnesium, and total antioxidant capacity as potential mediatory variables was studied.

Methods

It was an individually matched case–control study in which 330 depressed and healthy subjects were recruited for the extraction of dietary patterns; psychiatrists diagnosed major depressive disorder, using the criteria of the Diagnostic and Statistical Manual of Mental Disorders. Serum vitamin D and aforementioned biomarkers were measured for a number of randomly selected depressed and healthy individuals. We conducted mediatory analysis by regression models.

Results

Healthy and unhealthy dietary patterns were associated with the lower and higher odds of depression (OR 0.39, CI 0.17–0.92 and OR 2.6, CI 1.04–6.08), respectively. A significant relationship between serum vitamin D with depression after adjusting for potential confounders was observed as well (OR 0.93, CI 0.87–0.99). According to the mediatory analysis the unhealthy dietary patterns were related to depression via altering the serum vitamin D concentration.

Conclusion

This study showed that vitamin D deficiency mediates the relationship between unhealthy dietary patterns and depression. However, to get a clearer result further prospective studies are required.
Yolk sac tumor differentiation in urothelial carcinoma of the urinary bladder: a case report and differential diagnosis
Authors: Espejo-Herrera Nadia , Condom-Mundó Enric
Published: June 2020

Background

Yolk sac tumor (YST) is a germ cell neoplasm that arises predominantly in the gonads, but can also derive from somatic neoplasms in extragonadal locations. These latter cases have been documented in several organs, although reports from the urinary tract are limited. To our knowledge, this is the first report of a bladder urothelial carcinoma with a predominant component of YST differentiation.

Case presentation

We present a unique case of a 76-year-old man with a recurrent urinary bladder tumor, initially interpreted as a high grade urothelial carcinoma with glandular differentiation. In the recurrent tumor, diverse histological patterns were identified, including glandular, hepatoid and sarcomatoid. This tumor showed positivity for AFP, GLP3 and SALL4, and negativity for CK7 and EMA. Fluorescent in situ hybridization study showed a polysomic pattern of chromosome 12. All these findings led to the final diagnosis of a YST derived from urothelial carcinoma.

Conclusions

YST differentiation should be considered in the differential diagnosis of a high grade urothelial carcinoma, particularly when glandular and other unusual patterns are observed.
Effectiveness of guideline dissemination and implementation strategies on health care professionals’ behaviour and patient outcomes in the cancer care context: a systematic review
Authors: Tomasone Jennifer R. , Kauffeldt Kaitlyn D. , Chaudhary Rushil , Brouwers Melissa C.
Published: June 2020

Background

Health care professionals (HCPs) use clinical practice guidelines (CPGs) to make evidence-informed decisions regarding patient care. Although a large number of cancer-related CPGs exist, it is unknown which CPG dissemination and implementation strategies are effective for improving HCP behaviour and patient outcomes in a cancer care context. This review aimed to determine the effectiveness of CPG dissemination and/or implementation strategies among HCPs in a cancer care context.

Methods

A comprehensive search of five electronic databases was conducted. Studies were limited to the dissemination and/or implementation of a CPG targeting both medical and/or allied HCPs in cancer care. Two reviewers independently coded strategies using the Mazza taxonomy, extracted study findings, and assessed study quality.

Results

The search strategy identified 33 studies targeting medical and/or allied HCPs. Across the 33 studies, 23 of a possible 49 strategies in the Mazza taxonomy were used, with a mean number of 3.25 (SD = 1.45) strategies per intervention. The number of strategies used per intervention was not associated with positive outcomes. Educational strategies (n = 24), feedback on guideline compliance (n = 11), and providing reminders (n = 10) were the most utilized strategies. When used independently, providing reminders and feedback on CPG compliance corresponded with positive significant changes in outcomes. Further, when used as part of multi-strategy interventions, group education and organizational strategies (e.g. creation of an implementation team) corresponded with positive significant changes in outcomes.

Conclusions

Future CPG dissemination and implementation interventions for cancer care HCPs may benefit from utilizing the identified strategies. Research in this area should aim for better alignment between study objectives, intervention design, and evaluation measures, and should seek to incorporate theory in intervention design, so that behavioural antecedents are considered and measured; doing so would enhance the field’s understanding of the causal mechanisms by which interventions lead, or do not lead, to changes in outcomes at all levels.
Predicting survival in melanoma patients treated with concurrent targeted- or immunotherapy and stereotactic radiotherapy
Authors: Schaule Jana , Kroeze Stephanie G. C. , Blanck Oliver , Stera Susanne , Kahl Klaus H. , Roeder Falk , Combs Stephanie E. , Kaul David , Claes An , Schymalla Markus M. , Adebahr Sonja , Eckert Franziska , Lohaus Fabian , Abbasi-Senger Nasrin , Henke Guido , Szuecs Marcella , Geier Michael , Sundahl Nora , Buergy Daniel , Dummer Reinhard , Guckenberger Matthias
Published: June 2020

Background

Melanoma patients frequently develop brain metastases. The most widely used score to predict survival is the molGPA based on a mixed treatment of stereotactic radiotherapy (SRT) and whole brain radiotherapy (WBRT). In addition, systemic therapy was not considered. We therefore aimed to evaluate the performance of the molGPA score in patients homogeneously treated with SRT and concurrent targeted therapy or immunotherapy (TT/IT).

Methods

This retrospective analysis is based on an international multicenter database (TOaSTT) of melanoma patients treated with TT/IT and concurrent (≤30 days) SRT for brain metastases between May 2011 and May 2018. Overall survival (OS) was studied using Kaplan-Meier survival curves and log-rank testing. Uni- and multivariate analysis was performed to analyze prognostic factors for OS.

Results

One hundred ten patients were analyzed. 61, 31 and 8% were treated with IT, TT and with a simultaneous combination, respectively. A median of two brain metastases were treated per patient. After a median follow-up of 8 months, median OS was 8.4 months (0–40 months). The molGPA score was not associated with OS. Instead, cumulative brain metastases volume, timing of metastases (syn- vs. metachronous) and systemic therapy with concurrent IT vs. TT influenced OS significantly. Based on these parameters, the VTS score (volume-timing-systemic therapy) was established that stratified patients into three groups with a median OS of 5.1, 18.9 and 34.5 months, respectively (p = 0.001 and 0.03).

Conclusion

The molGPA score was not useful for this cohort of melanoma patients undergoing local therapy for brain metastases taking into account systemic TT/IT. For these patients, we propose a prognostic VTS score, which needs to be validated prospectively.
Impact of mouse strain and sex when modeling radiation necrosis
Authors: Boria Andrew J. , Perez-Torres Carlos J.
Published: June 2020

Background

Murine models are among the most common type of preclinical animal models used to study the human condition, but a wide selection of different mice is currently in use with these differences potentially compromising study results and impairing the ability to reconcile interstudy results. Our goal was to determine how the strain and sex of the mice selection would affect the development of radiation necrosis in our murine model of radiation-induced cerebral necrosis.

Methods

We generated this model by using a preclinical irradiator to irradiate a sub-hemispheric portion of the brain of mice with single-fraction doses of 80 Gy. Eight possible combinations of mice made up of two different with two substrains each (BALB/cN, BALB/cJ, C57BL/6 N, and C57BL/6 J) and both sexes were irradiated in this study. Radiation necrosis development was tracked up to 8 weeks with a 7 T Bruker MRI utilizing T2-weighted and post-contrast T1-weighted imaging. MRI results were compared to and validated with the use of histology which utilized a scale from 0 to 3 in ascending order of damage.

Results

Both time post-irradiation and strain (BALB/c vs C57BL/6) were significant factors affecting radiation necrosis development. Sex was in general not a statistically significant parameter in terms of radiation necrosis development.

Conclusion

Mouse strain thus needs to be considered when evaluating the results of necrosis models. However, sex does not appear to be a variable needing major consideration.
Preoperative hyaluronic acid injection modulates postoperative functional outcome in patients undergoing arthroscopic rotator cuff repair
Authors: Nakamura Yosuke , Gotoh Masafumi , Mitsui Yasuhiro , Nakamura Hidehiro , Ohzono Hiroki , Okawa Takahiro , Shiba Naoto
Published: June 2020

Background

Arthroscopic rotator cuff repair (ARCR) generally yields acceptable clinical results. Hyaluronic acid (HA), a high-molecular-weight polysaccharide, is present in the extracellular matrix of soft connective tissue and synovial fluid, and its injection is known to significantly improve pain and clinical outcomes after rotator cuff injury. Some studies have described the role of HA injections as conservative therapy for rotator cuff tears. Since the subacromial bursa is believed to be the main source of shoulder pain in rotator cuff tears, subacromial injection is frequently used before surgery; however, its relationship with the clinical outcome after surgery remains unclarified. Therefore, we aimed to examine effects of preoperative subacromial HA injection on postoperative clinical outcome in patients with ARCR.

Methods

Ninety-eight patients were divided into a HA injection group and a non-injection group. The functional outcome measured was the University of California, Los Angeles (UCLA) score. Univariate analysis was performed to obtain variables withpvalues less than 0.1; we then used propensity score analysis, adjusting for pre- and post-operative confounding factors.

Results

The UCLA scores of all patients significantly improved 1 year postoperatively (PO) (p< 0.05). Subacromial HA injections were performed in patients with worse preoperative function. Univariate analysis showed significantly greater improvements in the injection group than in the non-injection group in terms of preoperative UCLA score, trauma, diabetes mellitus, UCLA score 3 months PO, abduction strength 4 months PO, and internal rotation (IR) strength 6 and 12 months PO. Propensity score analysis demonstrated that UCLA scores 3 months PO and IR strength 12 months PO in the injection group were significantly greater than those in the non-injection group. There were no significant differences in postoperative re-tear rates between the groups. In sub-analysis of the injection group, propensity scores showed that concurrent use of local anesthetics did not affect the data, suggesting that HA was effective.

Conclusion

Subacromial injection was administered to patients with worse function before ARCR. Propensity score analysis successfully demonstrated that functional outcome after surgery was improved in patients who were administered this injection compared with patients who were not administered this injection before surgery.
Study of the tribological properties of surface structures using ultrashort laser pulses to reduce wear in endoprosthetics
Authors: Backes Lea Theresa , Oldorf Paul , Peters Rigo , Wendlandt Robert , Schnell Georg , Schulz Arndt-Peter
Published: June 2020

Background

Loosening of prostheses and functional disorders represent a far-reaching problem in the clinic, and the long-term outcomes are essentially determined by wear. Despite all advances, up to 10% of prostheses still fail after 10 years. In particular, more active patients show increased revision rates.

Methods

The objective of this thesis is to examine whether the applied microstructures of the articulating surfaces can lead to a reduction in abrasion. Three different structural geometries (dimples, offset lines, grid lines) were defined. In an experimental test setup according to DIN ISO 6474 (Deutsches Institut für Normung, International Organization for Standardization), a tribological test of metal and ceramic pairings was performed using two-dimensional ring-on-disc (RoD) tests.

Results

In both material groups, the structuring had a positive effect on the wear behaviour. In the ceramic group, an abrasion reduction of 22.6% was achieved. However, it is important to take into account the limited informative value due to the hardness of the material. Two of the three Cobalt-Chrome-Molybdenum (CoCrMo) structure geometries (grids, offset lines) also showed a significant reduction in abrasion compared to the reference group, with a maximum wear reduction of 55.5%.

Conclusion

By reducing abrasion, surface structuring could be used to extend the life of prostheses and minimise the number of revisions.
Nonstandard usage of a left ventricular assist device in a patient with severe heart failure complicated by pulmonary artery thrombosis - case report
Authors: Pacholewicz Jerzy , Leonik Szymon , Sojka Maciej , Nadziakiewicz Paweł
Published: June 2020

Background

Heart failure complicated by pulmonary embolism is an extremely rare condition described in the literature. We report a case of very young patient with advanced heart failure against the background of dilated cardiomyopathy of unknown etiology with the presence of blood clots in both ventricles.

Case presentation

The course of treatment was complicated by acute pulmonary embolism. In emergency setting the patient was qualified for combine surgery pulmonary embolization and implantation of a continuous flow pump as a bridge for heart transplantation. The post-operative course is described in detail as well as reimplantation of the pump due to early thrombosis.

Conclusions

Performed surgical procedures combined with alteration in anticoagulant drugs was sufficient to stabilize the clinical condition.
Minimally invasive beating heart technique for mitral valve surgery in patients with previous sternotomy and giant left ventricle
Authors: Zhang Hang , Xu Hua-shan , Wen Bing , Zhao Wen-zeng , Liu Chao
Published: June 2020

Purpose

To analyze the efficacy of minimally invasive beating heart technique for mitral valve surgery in the cardiac patients with previous sternotomy and giant left ventricle.

Methods

Eighty cardiac patients with previous sternotomy and giant left ventricle according to the diagnostic criteria that left ventricular end diastolic diameter (LVEDD) was ≥70 mm, who underwent mitral valve surgery at our center from January 2006 to January 2019 were analyzed. We divided all patients into minimally invasive beating heart technique group (n = 30) and conventional median resternotomy arrested heart technique group (n = 50) according to the surgical methods. Preoperative, intraoperative, and postoperative variables were compared between two groups.

Results

Minimally invasive beating heart technique compared to the conventional median resternotomy arrested heart technique for mitral valve surgery in the cardiac patients with previous sternotomy and giant left ventricle had significant differences in operation time(P = 0.002), cardiopulmonary bypass (CPB) time(P < 0.001), intraoperative blood loss(P < 0.001), postoperative transfusion ratio(P = 0.01), postoperative transfusion amount(P < 0.001), postoperative drainage volume(P = 0.001), extubation time(P = 0.04), intensive care unit (ICU) stay time(P = 0.04) and postoperative hospital stay time(P < 0.001), but no significant differences in re-exploration for bleeding, postoperative 30-day mortality, postoperative complications and 6 months postoperative echocardiographic parameters.

Conclusions

Using the method of minimally invasive beating heart technique for mitral valve surgery in the cardiac patients with previous sternotomy and giant left ventricle is effective and reliable, meanwhile reduce the operation time and CPB time, decrease the transfusion ratio and transfusion amount, shorten postoperative ICU stay and hospital stay time, promote the early extubation so that accelerate the patients’ early recovery.

All of these show a benefit of minimally invasive beating heart technique compared to conventional median resternotomy arrested heart technique.
Efficacy of acupuncture in the prevention and treatment of chemotherapy-induced nausea and vomiting in patients with advanced cancer: a multi-center, single-blind, randomized, sham-controlled clinical research
Authors: Li Qi-Wei , Yu Ming-Wei , Wang Xiao-Min , Yang Guo-Wang , Wang Huan , Zhang Chen-Xi , Xue Na , Xu Wei-Ru , Zhang Yi , Cheng Pei-Yu , Yang Lin , Fu Qi , Yang Zhong
Published: June 2020

Background

Chemotherapy-induced nausea and vomiting (CINV) is a common and distressing side effect. We conducted this clinical trial to compare the effectiveness of true acupuncture vs. sham acupuncture in controlling chemotherapy-induced nausea and vomiting (CINV) among patients with advanced cancer.

Methods

A total of 134 participants were randomly allocated into true acupuncture (TA) (n = 68) and sham acupuncture (SA) (n = 66) groups. Participants in both groups received acupuncture session twice on the first day of chemotherapy, and once consecutively on the following 4 days. The primary outcome was using the Common Terminology Criteria for Adverse Events (CTCAE) to assess CINV. The secondary outcome measures were the Eastern Cooperative Oncology Group score (ECOG), Simplified Nutritional Appetite Questionnaire (SNAQ), and Hospital Anxiety and Depression scale (HADS).

Results

Compared to the SA group, the TA group didn’t show significant improvement in complete response rates of chemotherapy-induced nausea and vomiting (all P > 0.05). However, the TA group could modestly reduce the severity of nausea (from day-3 to day-21, P < 0.05) or vomiting (from day-4 to day-21, P < 0.05), which is notably superior to the control group. Besides, TA promoted the nutritional status of patients with a significantly higher score comparing to the SA group on day 14 (21.82 vs.20.12, P = 0.003) and day 21 (22.39 vs. 20.43, P = 0.001). No apparent differences were found in anxiety and depression assessment between these groups. Participants in both groups were well tolerant of acupuncture therapy. There was no adverse event occurs in our study.

Conclusion

Acupuncture as an adjunctive approach could alleviate the severity of chemotherapy-induced nausea and vomiting compared to the sham control, even though the effect of acupuncture in preventing CINV occurring is relatively modest.
To what degree are orphan drugs patient-centered? A review of the current state of clinical research in rare diseases
Authors: Lanar Sally , Acquadro Catherine , Seaton James , Savre Isabelle , Arnould Benoit
Published: June 2020

Background

Over the past 30 years, the healthcare industry has increasingly turned its attention to rare diseases. Regulators have emphasized the need for clinical research in this area to be patient-centered. However, there is a lack of evidence concerning whether this need is actually met. In this paper, we aim to address this gap.

Methods

First, we describe the state of patient-centricity in clinical research in rare diseases based on a targeted literature review. Second, we discuss recommendations from scientific bodies on patient-reported outcome (PRO) measures in rare diseases. Third, we analyze data collected from EMA’s and FDA’s websites concerning rare disease labeling claims and data fromClinicaltrials.govconcerning the use of PRO measures in rare disease pivotal trials. Fourth, we perform an exhaustive literature review on the use of PRO measures in the pharmaceutical industry, including all phases of clinical research, observational/registry studies, and instrument development and validation.

Results

There is limited information on rare disease patient engagement in study design, recruitment, and retention. None of the initiatives describing methods for developing PRO measures in rare diseases provide the clear guidance clinical researchers need. Only 17.4% of orphan drug labels contain a PRO measure. Less than half of pivotal trials in orphan drugs have a PRO measure as a primary or a secondary endpoint. Although the number of publications about PRO measures in rare diseases has risen in the past fifteen years, our results indicate that substantial improvements are needed to achieve patient-centricity.

Conclusions

The nature and extent of patient engagement in rare disease research is under-documented. The current paradigm for developing and using PRO measures in clinical research is failing to meet the needs of rare disease patients. Not only are PROs rarely used as high-level endpoints in clinical trials or taken into account in labeling claims, they are also under-researched overall – there are too few measures for the multitude of rare diseases. We call for a clear guidance on patient engagement and suggest a realistic approach to the adaptation of PRO strategy to the specific context of clinical research in rare diseases.
Comparison of Streptococcus halichoeri isolates from canine and fur animal infections: biochemical patterns, molecular characteristics and genetic relatedness
Authors: Eklund Marjut , Aaltonen Kirsi , Sironen Tarja , Raunio-Saarnisto Mirja , Grönthal Thomas , Nordgren Heli , Pitkälä Anna , Vapalahti Olli , Rantala Merja
Published: June 2020

Background

Streptococcus halichoeri infections have been reported in grey seals, a European badger, a Stellar sea lion and humans, but its presence in companion and fur animals is unknown. Since 2010, S. halichoeri-like bacteria (SHL) have been isolated from fur animals and dogs in Finland. Our aim was to retrospectively investigate laboratory records for SHL from canine and fur animal infections, characterize the isolates and compare their genetic relatedness in relation to three reference strains: CCUG 48324T, originating from a grey seal, and strains 67100 and 61265, originally isolated from humans.

Results

A total of 138 and 36 SHLs from canine and fur animal infections, respectively, were identified in the laboratory records. SHL was commonly associated with skin infections, but rarely as the only species. A set of 49 canine and 23 fur animal SHLs were further characterized. MALDI-TOF confirmed them as being S. halichoeri. The growth characteristics were consistent with the original findings, but isolates were catalase positive. In total, 17 distinct API 20 Strep patterns were recorded among all 75 isolates tested, of which pattern 5563100 was the most common (n = 30). Antimicrobial resistance to erythromycin and clindamycin was common in canine isolates, but rare in fur animal isolates. Three clusters were observed by PFGE, and 16S rRNA sequencing revealed 98.1–100% similarities with the human strains and 98.1–99.5% with the seal strain. A phylogenetic tree of concatenated 16S rRNA and rpoB revealed closely related isolates with two clades. Fifteen canine isolates were identical to the human strains based on concatenated 16S rRNA and rpoB sequencing.

Conclusions

Streptococcus halichoeri appears to be quite a common bacterial species in the skin of dogs and fur animals. The clinical significance of S. halichoeri is uncertain, as it was rarely isolated as a monoculture. No apparent temporal or spatial clustering was detected, but isolates from different sources were genetically very similar. Because many canine isolates were genetically similar to the human reference strains, transmission between dogs and humans may be possible. WGS sequencing of strains from different sources is needed to further investigate the epidemiology and virulence of S. halichoeri.
Championing survival: connecting the unknown network of responders to address out-of-hospital cardiac arrest
Authors: McBride Ronan , Ski Chantal F. , Thompson David R. , Quinn Tom , Wilson Mark H.
Published: June 2020

Early intervention for out-of-hospital cardiac arrest (OHCA) presents a challenge for Emergency Medical Services (EMS) across Europe. Strategies designed to address this include education and training initiatives for citizens and building CPR skills capacity and awareness amongst health care professionals. However, there is a need to improve access to volunteer first responders who can commence CPR and defibrillate before the arrival of EMS. In the UK, initiatives such GoodSAM have integrated crowdsourcing technology with ambulance services to allow them autonomy in alerting responders to OHCAs which is parallel to an EMS dispatch. These services are building capacity to improve the initial ‘call for help’ and time to commence CPR and defibrillation if indicated. The next step is to identify and implement appropriate methods for public engagement, involvement and eventual networking of resources with statutory bodies such as local EMS. As crowdsourcing volunteer responders is at an early stage, there is a need to determine whether crowdsourcing is associated with patient outcomes, what its impact is on those responding to OHCA, whether it facilitates or impedes current services, and whether it is a safe and cost effective way to involve citizens to intervene in the community during cardiac arrest or other medical emergencies? Addressing such issues is likely to provide further insight into the role and effectiveness of new technologies and their potential impact on the wider community.
Changes to aspects of ongoing randomised controlled trials with fixed designs
Authors: Coskinas Xanthi , Simes John , Schou Manjula , Martin Andrew James
Published: June 2020

Background

Despite careful planning, changes to some aspects of an ongoing randomised clinical trial (RCT), with a fixed design, may be warranted. We sought to elucidate the distinction between legitimate versus illegitimate changes to serve as a guide for less experienced clinical trialists and other stakeholders.

Methods

Using data from a large trial of statin therapy for secondary prevention, we generated a set of simulated trial datasets under the null hypothesis (H0) and a set under an alternative hypothesis (H1). Through analysis of these simulated trials, we assessed the performance of the strategy of changing aspects of the design/analysis with knowledge of treatment allocation (illegitimate) versus the strategy of making changes without knowledge of treatment allocation (legitimate). Performance was assessed using the type 1 error, as well as measures of absolute and relative bias in the treatment effect.

Results

Illegitimate changes led to a relative bias of 61% under H1, and a type 1 error rate under H0 of 23%—well in excess of the 5% significance level targeted. Legitimate changes produced unbiased estimates under H1 and did not inflate the type 1 error rate under H0.

Conclusions

Changes to pre-specified aspects of the design and analysis of an ongoing RCT may be a necessary response to unforeseen circumstances. Such changes risk introducing a bias if undertaken with knowledge of treatment allocation. Legitimate changes need to be adequately documented to provide assurance to all stakeholders of their validity.
MOdified DIagnostic strateGy to safely ruLe-out pulmonary embolism In the emergency depArtment: study protocol for the Non-Inferiority MODIGLIANI cluster cross-over randomized trial
Authors: Philippon Anne-Laure , Dumont Margaux , Jimenez Sonia , Salhi Sarah , Cachanado Marine , Durand-Zaleski Isabelle , Simon Tabassome , Freund Yonathan
Published: June 2020

Introduction

In the work-up strategy for pulmonary embolism (PE) in the ED, the recently introduced YEARS rule allows the raising of the D-dimer threshold to 1000 ng/ml in patients with no signs of deep venous thrombosis and no hemoptysis and in whom PE is not the most likely diagnosis. However, this decision rule has never been prospectively compared to the usual strategy. Furthermore, it is unclear if the YEARS rule can be used on top of the Pulmonary Embolism Rule-out Criteria (PERC). We aim to assess the non-inferiority of YEARS compared to current guidelines to rule out PE among PERC-positive ED patients with suspicion of PE.

Methods/design

The MODIGLIANI study is a multicenter, European, non-inferiority, cluster-randomized, two periods cross-over, controlled trial. Each center will be randomized for the sequence of two 4-month periods: intervention (MOdified Diagnostic Strategy: MODS) followed by control (usual care), or control followed by intervention with 1 month of “wash-out” between the two periods. In the control period, the threshold will be as usual (500 ng/ml for patients aged 50 years or younger and age × 10 for older patients). In the MODS period, the threshold of D-dimers to rule out PE will be raised to 1000 ng/ml if no item of the YEARS score is present or will remain unchanged otherwise. Patients will be included if they have a suspicion of PE, defined as chest pain, dyspnea, or syncope. Non-inclusion criteria comprise a high clinical probability of PE or PERC-negative patients with low clinical probability.

Ethics and dissemination

The study has received the following approvals: Comité de protection des personnes Ile de France XI (France) and Comité de Ética de la Investigación con medicamentos del Hospital Clínic de Barcelona (Spain). Results will be made available to all included participants and other researchers.

Trial registration

ClinicalTrials.gov, NCT04032769. Registered on 24 July 2019.
Umbilical cord blood therapy to prevent progression of COVID-19 related pneumonia: a structured summary of a study protocol for a pilot randomised controlled trial
Authors: Malhotra Atul , Ernest David , Rogers Benjamin A. , Haylock David , Watt Ashalyn , Moeneclaey Guy , Jenkin Graham
Published: June 2020

Objectives

Objective: To undertake a pilot, feasibility RCT of umbilical cord blood derived cell therapy for treatment of adult patients infected with SARS-CoV-2 virus related moderate-to-severe pneumonia to prevent progression to severe ARDS.

Hypothesis: Expanded cord blood derived cell therapy will be feasible, well tolerated and show potential efficacy in the treatment of acute COVID-19 related moderate to severe pneumonia in adult patients because of their powerful anti-inflammatory and immunomodulatory properties.

Trial design

Pilot, parallel design randomised controlled trial.

Participants

The trial will recruit 24 hospitalised patients with confirmed SARS-CoV-2 infection and pneumonia from July to December 2020 at Monash Medical Centre in Melbourne, Australia.

Intervention and comparator

Intervention: Intravenous injection of expanded umbilical cord blood cells at a dose of 5 million cells/kg (maximum dose - 500 million cells). Cell infusion will occur over 30-60 minutes through a peripheral intravenous cannula. Standard supportive care will continue as needed.

Comparator: Standard supportive care.

Main outcomes

Safety and tolerability of cell administration within first 24 hours of administration; clinical improvement on a seven-category clinical improvement ordinal scale.

Randomisation

Randomisation will be done using computer generated allocation to intervention/ control groups in a 1:1 ratio (in blocks of 6) using sealed opaque envelopes.

Blinding (masking)

This will be an unblinded study, given that it is the first study using expanded cord blood cells in COVID-19 patients. There will be no placebo infusion.

Numbers to be randomised (sample size)

Twelve participants in each group. Total n=24.

Trial Status

CBC-19 protocol v2, dated 23rd April 2020. Recruitment has not started yet. Estimated recruitment timeline is between 1st July – 31st December 2020.

Trial registration

Australian New Zealand Clinical Trials Registry, ACTRN12620000478910, registered 16th April 2020.

Full protocol

The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
Effect of transcranial direct current stimulation on sports performance for two profiles of athletes (power and endurance) (COMPETE): a protocol for a randomised, crossover, double blind, controlled exploratory trial
Authors: Grandperrin Yohan , Grosprêtre Sidney , Nicolier Magali , Gimenez Philippe , Vidal Chrystelle , Haffen Emmanuel , Bennabi Djamila
Published: June 2020

Background

Transcranial direct current stimulation (tDCS) is promising for improving motor and cognitive performance. Nevertheless, its mechanisms of action are unclear and need to be better characterised according to the stimulated brain area and the type of exercise performed.

Methods/design

This is a double-blind crossover study, organised into two parts: the first is to assess the effects of tDCS on explosive performance (jump task) and the second is to assess the effects on endurance performance (cycling time trial task). Participants, who are recreationally active or athletes (parkour practitioners, cyclists), will receive two active tDCS sessions (over the left dorsolateral prefrontal cortex and right motor cortex) and one sham tDCS session (part A), or two sequences (one active and one sham) of two daily tDCS sessions over 5 days (part B). Motor and cognitive performance will be compared before and after tDCS sessions (part A), and before and after the first session, after the last session and at day 12 and day 30 of each tDCS sequence (part B).

Discussion

This study investigates the acute and repeated effects of tDCS on the motor and cognitive performance of healthy subjects. It will try to evaluate if tDCS could be considered as a neuroenhancement technology according to the physical task investigated (endurance versus explosive).

Trial registration

ClinicalTrials.gov,NCT03937115. Registered on 3 May 2019; retrospectively registered.
Purification and immobilization of engineered glucose dehydrogenase: a new approach to producing gluconic acid from breadwaste
Authors: Karagoz Pinar , Mandair Ravneet , Manayil Jinesh Cherukkattu , Lad Jai , Chong Katie , Kyriakou Georgios , Lee Adam F. , Wilson Karen , Bill Roslyn M.
Published: June 2020

Background

Platform chemicals are essential to industrial processes. Used as starting materials for the manufacture of diverse products, their cheap availability and efficient sourcing are an industrial requirement. Increasing concerns about the depletion of natural resources and growing environmental consciousness have led to a focus on the economics and ecological viability of bio-based platform chemical production. Contemporary approaches include the use of immobilized enzymes that can be harnessed to produce high-value chemicals from waste.

Results

In this study, an engineered glucose dehydrogenase (GDH) was optimized for gluconic acid (GA) production. Sulfolobus solfataricus GDH was expressed in Escherichia coli. The Km and Vmax values for recombinant GDH were calculated as 0.87 mM and 5.91 U/mg, respectively. Recombinant GDH was immobilized on a hierarchically porous silica support (MM-SBA-15) and its activity was compared with GDH immobilized on three commercially available supports. MM-SBA-15 showed significantly higher immobilization efficiency (> 98%) than the commercial supports. After 5 cycles, GDH activity was at least 14% greater than the remaining activity on commercial supports. Glucose in bread waste hydrolysate was converted to GA by free-state and immobilized GDH. After the 10th reuse cycle on MM-SBA-15, a 22% conversion yield was observed, generating 25 gGA/gGDH. The highest GA production efficiency was 47 gGA/gGDH using free-state GDH.

Conclusions

This study demonstrates the feasibility of enzymatically converting BWH to GA: immobilizing GDH on MM-SBA-15 renders the enzyme more stable and permits its multiple reuse.
Protist enteroparasites in wild boar (Sus scrofa ferus) and black Iberian pig (Sus scrofa domesticus) in southern Spain: a protective effect on hepatitis E acquisition?
Authors: Rivero-Juarez Antonio , Dashti Alejandro , López-López Pedro , Muadica Aly Salimo , Risalde Maria de los Angeles , Köster Pamela C. , Machuca Isabel , Bailo Begoña , de Mingo Marta Hernández , Dacal Elena , García-Bocanegra Ignacio , Saugar José M. , Calero-Bernal Rafael , González-Barrio David , Rivero Antonio , Briz Verónica , Carmena David
Published: June 2020

Background

Several studies have independently evaluated the occurrence of hepatitis E virus (HEV) and enteroparasites in swine, but no surveys have been conducted to jointly assess the prevalence and genetic diversity of enteroparasites in pigs and wild boars, their sympatric transmission between hosts, and their potential interaction with HEV.

Methods

We prospectively collected serum and faecal samples from black Iberian domestic pigs and wild boars from southern Spain between 2015‒2016. We evaluated for HEV in serum and faeces, and for the presence of enteroparasites (Giardia duodenalis, Cryptosporidium spp., Blastocystis sp., Neobalantidium coli and Strongyloides spp.) in the same faecal samples. The prevalence of each intestinal parasite species was calculated.

Results

A total of 328 animals (56.7% black Iberian pigs and 43.3% wild boars) were included in the study. The overall global prevalence of HEV in serum was 16.8%. The overall global prevalence of each enteroparasite species was 19.5% for G. duodenalis, 8.2% for Cryptosporidium spp., 41.8% for Blastocystis sp., 31.4% for N. coli, and 8.8% for Strongyloides spp. HEV-infected animals showed a significantly lower prevalence of G. duodenalis (3.2 vs 20%; P = 0.002) and Blastocystis sp. (38.7 vs 80%; P < 0.001) than those uninfected by HEV. Animals carrying G. duodenalis and Blastocystis sp. infections showed a significantly lower rate of HEV infection than those not harbouring these enteroparasites (P < 0.001).

Conclusions

Our study found a high prevalence of enteroparasites in black Iberian pigs and wild boars in southern Spain, suggesting a sympatric co-transmission of some of the species investigated. It is suggested that extracellular G. duodenalis and Blastocystis sp. might have a protective effect on HEV acquisition in swine.
Mapping the canine vector-borne disease risk in a Mediterranean area
Authors: Kostopoulou Despoina , Gizzarelli Manuela , Ligda Panagiota , Foglia Manzillo Valentina , Saratsi Katerina , Montagnaro Serena , Schunack Bettina , Boegel Annette , Pollmeier Matthias , Oliva Gaetano , Sotiraki Smaragda
Published: June 2020

Background

The aim of this study was to determine exposure to vector-borne pathogens (VBPs) in populations of dogs living on Greek islands in the Ionian and Aegean seas.

Methods

In total, 1154 dogs with different lifestyles and of varying ages and breeds were randomly sampled and examined for the presence of clinical signs compatible with canine vector-borne diseases (CVBDs). Blood was collected from each individual animal. For the detection of antibodies against Leishmania spp., the WITNESS® Leishmania test was performed, and positive samples were further examined with indirect enzymatic immunoassay (ELISA). Antibodies to Borrelia burgdorferi, Ehrlichia canis or E. ewingii, as well as Anaplasma phagocytophilum or A. platys were investigated using the Snap® 4Dx® Plus test. Positive Ehrlichia spp. and Anaplasma spp. samples were further examined using an indirect ELISA for further identification of the species.

Results

In total, 25.6% of dogs were exposed to at least one of the pathogens investigated, with seroprevalences varying regionally. Of these seropositive dogs, 27.4% displayed clinical signs suggestive of CVBDs, such as cutaneous lesions, enlarged lymph nodes, pale mucous membranes, onychogryphosis and weight loss. The overall seroprevalence detected using the rapid tests was 15.3% for Leishmania spp., whereas 2.3% of the examined dogs were found to be positive for Anaplasma spp. and 7.5% for Ehrlichia spp. while B. burgdorferi was not detected. Twenty-four samples positive to A. phagocytophilum by ELISA were analysed by PCR for the presence of Anaplasma DNA. PCR and sequencing results showed the presence of A. platys DNA in 4 samples and E. canis DNA in 4 samples. The remaining samples (66.7%) were negative.

Conclusions

In the present study, exposure of dogs to VBPs was shown in the geographical areas investigated. Results confirm that on Greek islands VBPs represent a constant health risk for both native and visiting dogs, suggesting the presence of distinct “hot-spots” of VBP infections on different islands. In order to reduce the risk of transmission and the spread to non-endemic regions, the protection of dogs through use of repellents and vaccines, together with owner education, seem to be of paramount importance.