bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or “Immuno-Fairy Tales”?
Authors: Labro Marie-Thérése 
Published: October 2018

SUMMARYProfessional phagocytes (polymorphonuclear neutrophils and monocytes/macrophages) are a main component of the immune system. These cells are involved in both host defenses and various pathological settings characterized by excessive inflammation. Accordingly, they are key targets for immunomodulatory drugs, among which antibacterial agents are promising candidates. The basic and historical concepts of immunomodulation will first be briefly reviewed. Phagocyte complexity will then be unravelled (at least in terms of what we know about the origin, subsets, ambivalent roles, functional capacities, and transductional pathways of this cell and how to explore them). The core subject of this review will be the many possible interactions between antibacterial agents and phagocytes, classified according to demonstrated or potential clinical relevance (e.g., neutropenia, intracellular accumulation, and modulation of bacterial virulence). A detailed review of direct in vitro effects will be provided for the various antibacterial drug families, followed by a discussion of the clinical relevance of these effects in two particular settings: immune deficiency and inflammatory diseases. The prophylactic and therapeutic use of immunomodulatory antibiotics will be considered before conclusions are drawn about the emerging (optimistic) vision of future therapeutic prospects to deal with largely unknown new diseases and new pathogens by using new agents, new techniques, and a better understanding of the phagocyte in particular and the immune system in general.
Fungal and Parasitic Infections of the Eye
Authors: Klotz Stephen A. , Penn Christopher C. , Negvesky Gerald J. , Butrus Salim I. 
Published: October 2018

SUMMARYThe unique structure of the human eye as well as exposure of the eye directly to the environment renders it vulnerable to a number of uncommon infectious diseases caused by fungi and parasites. Host defenses directed against these microorganisms, once anatomical barriers are breached, are often insufficient to prevent loss of vision. Therefore, the timely identification and treatment of the involved microorganisms are paramount. The anatomy of the eye and its surrounding structures is presented with an emphasis upon the association of the anatomy with specific infection of fungi and parasites. For example, filamentous fungal infections of the eye are usually due to penetrating trauma by objects contaminated by vegetable matter of the cornea or globe or, by extension, of infection from adjacent paranasal sinuses. Fungal endophthalmitis and chorioretinitis, on the other hand, are usually the result of antecedent fungemia seeding the ocular tissue. Candida spp. are the most common cause of endogenous endophthalmitis, although initial infection with the dimorphic fungi may lead to infection and scarring of the chorioretina. Contact lens wear is associated with keratitis caused by yeasts, filamentous fungi, and Acanthamoebae spp. Most parasitic infections of the eye, however, arise following bloodborne carriage of the microorganism to the eye or adjacent structures.
Vancomycin-Resistant Enterococci
Authors: Cetinkaya Yesim , Falk Pamela , Mayhall C. Glen 
Published: October 2018

SUMMARYAfter they were first identified in the mid-1980s, vancomycin-resistant enterococci (VRE) spread rapidly and became a major problem in many institutions both in Europe and the United States. Since VRE have intrinsic resistance to most of the commonly used antibiotics and the ability to acquire resistance to most of the current available antibiotics, either by mutation or by receipt of foreign genetic material, they have a selective advantage over other microorganisms in the intestinal flora and pose a major therapeutic challenge. The possibility of transfer of vancomycin resistance genes to other gram-positive organisms raises significant concerns about the emergence of vancomycin-resistant Staphylococcus aureus. We review VRE, including their history, mechanisms of resistance, epidemiology, control measures, and treatment.
Pathogenic Roles for Fungal Melanins
Authors: Jacobson Eric S. 
Published: October 2018

SUMMARYMelanins represent virulence factors for several pathogenic fungi; the number of examples is growing. Thus, albino mutants of several genera (in one case, mutated precisely in the melanizing enzyme) exhibit decreased virulence in mice. We consider the phenomenon in relation to known chemical properties of melanin, beginning with biosynthesis from ortho-hydroquinone precursors which, when oxidized enzymatically to quinones, polymerize spontaneously to melanin. It follows that melanizing intermediates are cross-linking reagents; melanization stabilizes the external cell wall against hydrolysis and is thought to determine semipermeability in the osmotic ram (the appressorium) of certain plant pathogens. Polymeric melanins undergo reversible oxidation-reduction reactions between cell wall-penetrating quinone and hydroquinone oxidation states and thus represent polymeric redox buffers; using strong oxidants, it is possible to titrate the melanin on living cells and thereby demonstrate protection conferred by melanin in several species. The amount of buffering per cell approximately neutralizes the amount of oxidant generated by a single macrophage. Moreover, the intermediate oxidation state, the semiquinone, is a very stable free radical and is thought to trap unpaired electrons. We have suggested that the oxidation state of external melanin may be regulated by external Fe(II). An independent hypothesis holds that in Cryptococcus neoformans, an important function of the melanizing enzyme (apart from melanization) is the oxidation of Fe(II) to Fe(III), thereby forestalling generation of the harmful hydroxyl radical from H2O2. Thus, problems in fungal pathogenesis have led to evolving hypotheses regarding melanin functioning.
The Evolution of Genotyping Strategies To Detect, Analyze, and Control Transmission of Tuberculosis
Authors: García De Viedma Darío , Pérez-Lago Laura 
Published: October 2018

ABSTRACT

The introduction of genotypic tools to analyze
Mycobacterium tuberculosis
isolates has transformed our knowledge of the transmission dynamics of this pathogen. We discuss the development of the laboratory methods that have been applied in recent years to study the epidemiology of
M. tuberculosis
. This review integrates two approaches: on the one hand, it considers how genotyping techniques have evolved over the years; and on the other, it looks at how the way we think these techniques should be applied has changed. We begin by examining the application of fingerprinting tools to suspected outbreaks only, before moving on to universal genotyping schemes, and finally we describe the latest real-time strategies used in molecular epidemiology. We also analyze refined approaches to obtaining epidemiological data from patients and to increasing the discriminatory power of genotyping by techniques based on genomic characterization. Finally, we review the development of integrative solutions to reconcile the speed of PCR-based methods with the high discriminatory power of whole-genome sequencing in easily implemented formats adapted to low-resource settings. Our analysis of future considerations highlights the need to bring together the three key elements of high-quality surveillance of transmission in tuberculosis, namely, speed, precision, and ease of implementation.
Newborn self-inflating manual resuscitators: precision robotic testing of safety and reliability
Authors: Tracy Mark B , Halliday Robert , Tracy Sally K , Hinder Murray K 
Published: October 2018

AimA controlled bench test was undertaken to determine the performance variability among a range of neonatal self-inflating bags (SIB) compliant with current International Standards Organisation (ISO).IntroductionUse of SIB to provide positive pressure ventilation during newborn resuscitation is a common emergency procedure. The United Nations programmes advocate increasing availability of SIB in low-income and middle-income nations and recommend devices compliant with ISO. No systematic study has evaluated variance in different models of neonatal SIB.Methods20 models of SIB were incrementally compressed by an automated robotic device simulating the geometry and force of a human hand across a range of precise distances in a newborn lung model. Significance was calculated using analysis of variance repeated measures to determine the relationship between distance of SIB compression and delivered ventilation. A pass/fail was derived from a composite score comprising: minimum tidal volume; coefficient of variation (across all compression distances); peak pressures generated and functional compression distance.ResultsTen out of the 20 models of SIB failed our testing methodology. Two models could not provide safe minimum tidal volumes (2.5–5 mL); six models exceeded safety inflation pressure limit >45 cm H2O, representing 6% of their inflations; five models had excessive coefficient of variation (>30% averaged across compression distances) and three models did not deliver inflation volumes >2.5 mL until approximately 50% of maximum bag compression distance was reached. The study also found significant intrabatch variability and forward leakage.ConclusionCompliance of SIBs with ISO standards may not guarantee acceptable or safe performance to resuscitate newborn infants.
Synthetic biodegradable alternatives to the use of the amniotic membrane for corneal regeneration: assessment of local and systemic toxicity in rabbits
Authors: Ramachandran Charanya , Sangwan Virender S , Ortega Ilida , Bhatnagar Upendra , Mulla Sadik Mohmad Abdulhamid , McKean Rob , MacNeil Sheila 
Published: October 2018

AimThe aim of this study was to assess the local and systemic response to poly-lactic co-glycolic acid (PLGA) 50:50 membranes, developed as synthetic biodegradable alternatives to the use of human donor amniotic membrane in the treatment of limbal stem cell deficiency.MethodsPLGA membranes of 2  cm diameter and 50  µm thickness were placed on one eye of rabbits and secured in place using fibrin glue and a bandage contact lens, suturing the eye close with a single stitch. Control animals were treated identically, with the absence of the membranes. Plain and microfabricated electrospun membranes (containing micropockets which roughly emulate the native limbal niche) were examined over 29 days. All animals were subjected to a detailed gross and histopathological observation as well as a detailed examination of the eye.ResultsApplication of the membranes both with and without microfabricated pockets did not adversely affect animal welfare. There was complete degradation of the membranes by day 29. The membranes did not induce any significant local or systemic toxicity. Conjunctival congestion and corneal vascularisation were noted in a few control and PLGA-treated animals. Intraocular pressure was normal and the retinal status was unaltered. The ocular surface was clear and intact in all animals by the end of 29  days.ConclusionMembranes of 50:50 PLGA can be safely applied to rabbit corneas without inducing any local or systemic toxicity and these break down completely within 29 days.
Arrabidaea chicafor oral mucositis in patients with head and neck cancer: a protocol of a randomised clinical trial
Authors: Queiroz Núbia de Cassia Almeida , Jorge Michelle Pedroza , Sousa Ilza Maria de Oliveira , Lima Carmen Silvia Passos , Matias Maria Christina de Miranda , Dal Rio Ana Cristina , Pereira Eduardo Baldon , Galassi Victória Hahn Kakas , de Carvalho João Ernesto , Galvao Tais Freire , Foglio Mary Ann 
Published: October 2018

IntroductionOral mucositis is an iatrogenic condition of erythematous inflammatory changes which tends to occur on buccal and labial surfaces, the ventral surface of the tongue, the floor of the mouth and the soft palate of patients receiving chemotherapy. This protocol of ongoing randomised parallel group clinical trial aims to access the therapeutic effect of an herbal gel containing 2.5%Arrabidaea chicaVerlot standardised extract on oral mucositis in patients with head and neck cancer compared with low-level laser therapy.Methods and analysisPatients with head and neck cancer held at Clinics Hospital of University of Campinas, Sao Paulo, who develop early signs/symptoms of oral mucositis are eligible. Baseline characteristics of participants include oral mucositis grade and quality of life assessments. Enrolment started in November 2017 with allocation of patients to one of the study groups by means of randomisation. Patients will be treated either withArrabidaea chicaor laser until wound healing. Monitoring includes daily assessment of mucositis grade and diameter measurement by photographs and millimetre periodontal probe. Treatments will be concluded once mucositis is healed. A blinded assessor will evaluate mucositis cure after referred by the study team. At this point, the gel tube will be weighed to indirectly assess patient’s compliance. At close-out, data will be analysed by a blinded researcher following the procedures described in the statistical analyses.Ethics and disseminationThis clinical trial was approved by the ethics committee of research in humans at the Faculty of Medical Sciences of University of Campinas (report no. 1,613,563/2016). Results from this trial will be communicated in peer-reviewed publications and scientific presentations.Trial registration numberRBR-5×4397.
Engineering standards for trauma and orthopaedic implants worldwide: a systematic review protocol
Authors: Henshaw Frederick , Karasouli Eleni , King Richard , Rahman Usama , Langton David , Madete June , Otsyeno Fred , Mutiso Vincent , Atinga John , Underwood Martin , Williams Mark , Metcalfe Andrew 
Published: October 2018

IntroductionDespite multiple scandals in the medical implant sector, premarket testing has been the attention of little published research. Complications related to new devices, such as the DePuy Articular Surface Replacement (ASR, DePuy Synthes, USA), have raised the issue of how designs are tested and whether engineering standards remain up to date with our understanding of implant biomechanics. Despite much work setting up national joint registries to improve implant monitoring, there have been few academic studies examining the premarket engineering standards new implants must meet. Emerging global economies mean that the markets have changed, and it is unknown to what degree engineering standards vary around the world. Governments, industry and independent regulatory bodies all produce engineering standards; therefore, the comparison of surgical implants across different manufacturers and jurisdictions is difficult. In this review, we will systematically collate and compare engineering standards for trauma and orthopaedic implants around the world. This will help inform patient, hospital and surgeon choice and provide an evidence base for future research in this area.Methods and analysisThis protocol is based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) guidelines. We will conduct a systematic review of trauma and orthopaedic engineering standards from four main sources of information as identified in our preliminary scoping searches: governments, industry, independent regulatory bodies and engineering and medical publications. Any current standard relevant to trauma and orthopaedic implants will be included. We will use a predefined search strategy and follow the recommendations of the Cochrane handbook where applicable. We will undertake a narrative synthesis with qualitative evaluation of homogeneity between engineering standards.Ethics and disseminationNo ethics approval is required as no primary data are being collected. The results will be made available by peer-reviewed publication and reported according to PRISMA-P guidelines.
Models of suicide in elderly: a protocol for a systematic review
Authors: Rostami Mohammad , Younesi Seyyed Jalal , Mohammadi Shahboulaghi Farahnaz , Malakouti Seyed Kazem , Foroughan Mahshid 
Published: October 2018

IntroductionThe rates of suicide in the elderly population are generally higher than other age groups. Models of suicide that explain the phenomenon of suicide in later life may have research, clinical and educational implications for the field of ageing. The primary purpose of this systematic review is to identify and review existing models of suicide that have a particular focus on the elderly.Methods and analysisThe authors intend reviewing the findings of observational studies including cohort studies, cross-sectional studies, case–control studies, and qualitative studies such as grounded theory designs which are published in Google Scholar, Scopus, PsycINFO, PubMed, Web of Science, Cochrane Database of Systematic Reviews and research-related journals. Models of suicide which specifically describe, explain and predict late life suicides will be included. Therapeutic, interventional and rehabilitation models, as well as models related to assisted suicide, will be excluded. The EndNote software will be employed for data management. Two independent reviewers will extract data. Methodological quality and the risk of bias of quantitative studies will be assessed using the Newcastle-Ottawa Scale and the Newcastle-Ottawa Scale adapted for cross-sectional studies, while that of qualitative studies will be assessed using the Critical Appraisal Skills Programme and the evaluative criteria of credibility, transferability, dependability and confirmability. The final report will present a range of models of suicide with a list of different subgroups.Ethics and publicationThere are no predictable ethical issues related to this study. The findings will be published in prestigious journals and presented at international and national conferences.PROSPERO registration numberCRD42017070982.
Regional differences in endoscopic sinus surgery in Finland: a nationwide register-based study
Authors: Toppila-Salmi Sanna , Rihkanen Heikki , Arffman Martti , Manderbacka Kristiina , Keskimaki Ilmo , Hytönen Maija L 
Published: October 2018

ObjectivesEndoscopic sinus surgery (ESS) is a common operation typically performed due to chronic rhinosinusitis (CRS). There are limited data on the nationwide ESS rate and factors contributing to its regional variation. The aim was to evaluate factors causing variation of ESS rate.DesignCross-sectional nationwide observational study.SettingA ll patients undergoing ESS in Finland 2013–2015.PopulationNationwide Finnish population aged 15 years or over.Main outcome measuresESS rate per 1000 inhabitants between 2013 and 2015 in all 21 hospital districts and independent factors for multilevel model analyses.MethodsWe used the Finnish register data of all patients with CRS who underwent ESS in 2013–2015. Patients aged under 15 years and those with ESS due to neoplasia were excluded. The age and gender standardised ESS rates were calculated, and multilevel Poisson regression models were used to evaluate variation in ESS in the 21 hospital districts. The likelihood ratio test was applied to assess the statistical significance of random components in the models.ResultsThe nationwide annual rate of ESS is 0.71 per 1000 people in Finland. Hospital district rates varied from 0.25/1000 (95% CI 0.18 to 0.32) to 1.15/1000 (95% CI 1.09 1.21). Compared with males, females undergo ESS significantly more frequently (57% of the procedures), more often due to CRS without nasal polyps, and at a younger age (mean age 44.2 and 46.2 years, correspondingly). Multilevel analyses showed that lower age (between 24 years and 45 years) and availability/ease of medical services were independently associated with higher ESS rates.ConclusionsThis study confirms marked regional variation in the ESS rate in Finland, explained only in part by patients’ age and differing availability of medical services. To analyse ESS across different CRS phenotypes or to compare quality registers on ESS properly, more research on regional variation is needed.
Better Outcomes for Older people with Spinal Trouble (BOOST) Trial: a randomised controlled trial of a combined physical and psychological intervention for older adults with neurogenic claudication, a protocol
Authors: Williamson Esther , Ward Lesley , Vadher Karan , Dutton Susan J , Parker Ben , Petrou Stavros , Hutchinson Charles E , Gagen Richard , Arden Nigel K , Barker Karen , Boniface Graham , Bruce Julie , Collins Gary , Fairbank Jeremy , Fitch Judith , French David P , Garrett Angela , Gandhi Varsha , Griffiths Frances , Hansen Zara , Mallen Christian , Morris Alana , Lamb Sarah E 
Published: October 2018

IntroductionNeurogenic claudication due to spinal stenosis is common in older adults. The effectiveness of conservative interventions is not known. The aim of the study is to estimate the clinical and cost-effectiveness of a physiotherapist-delivered, combined physical and psychological intervention.Methods and analysisThis is a pragmatic, multicentred, randomised controlled trial. Participants are randomised to a combined physical and psychological intervention (Better Outcomes for Older people with Spinal Trouble (BOOST) programme) or best practice advice (control). Community-dwelling adults, 65 years and over, with neurogenic claudication are identified from community and secondary care services. Recruitment is supplemented using a primary care-based cohort. Participants are registered prospectively and randomised in a 2:1 ratio (intervention:control) using a web-based service to ensure allocation concealment. The target sample size is a minimum of 402. The BOOST programme consists of an individual assessment and twelve 90 min classes, including education and discussion underpinned by cognitive behavioural techniques, exercises and walking circuit. During and after the classes, participants undertake home exercises and there are two support telephone calls to promote adherence with the exercises. Best practice advice is delivered in one to three individual sessions with a physiotherapist. The primary outcome is the Oswestry Disability Index at 12 months. Secondary outcomes include the 6 Minute Walk Test, Short Physical Performance Battery, Fear Avoidance Beliefs Questionnaire and Gait Self-Efficacy Scale. Outcomes are measured at 6 and 12 months by researchers who are masked to treatment allocation. The primary statistical analysis will be by ‘intention to treat’. There is a parallel health economic evaluation and qualitative study.Ethics and disseminationEthical approval was given on 3 March 2016 (National Research Ethics Committee number: 16/LO/0349). This protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials checklist. The results will be reported at conferences and in peer-reviewed publications using the Consolidated Standards of Reporting Trials guidelines. A plain English summary will be published on the BOOST website.Trial registration numberISRCTN12698674; Pre-results.