bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Emerging Amphibian Fungal Disease, Chytridiomycosis: A Key Example of the Global Phenomenon of Wildlife Emerging Infectious Diseases
Authors: Kolby Jonathan E. , Daszak Peter 
Published: May 2016

ABSTRACT

The spread of amphibian chytrid fungus,
Batrachochytrium dendrobatidis
, is associated with the emerging infectious wildlife disease chytridiomycosis. This fungus poses an overwhelming threat to global amphibian biodiversity and is contributing toward population declines and extinctions worldwide. Extremely low host-species specificity potentially threatens thousands of the 7,000+ amphibian species with infection, and hosts in additional classes of organisms have now also been identified, including crayfish and nematode worms.

Soon after the discovery of
B. dendrobatidis
in 1999, it became apparent that this pathogen was already pandemic; dozens of countries and hundreds of amphibian species had already been exposed. The timeline of
B. dendrobatidis
’s global emergence still remains a mystery, as does its point of origin. The reason why
B. dendrobatidis
seems to have only recently increased in virulence to catalyze this global disease event remains unknown, and despite 15 years of investigation, this wildlife pandemic continues primarily uncontrolled. Some disease treatments are effective on animals held in captivity, but there is currently no proven method to eradicate
B. dendrobatidis
from an affected habitat, nor have we been able to protect new regions from exposure despite knowledge of an approaching “wave” of
B. dendrobatidis
and ensuing disease.

International spread of
B. dendrobatidis
is largely facilitated by the commercial trade in live amphibians. Chytridiomycosis was recently listed as a globally notifiable disease by the World Organization for Animal Health, but few countries, if any, have formally adopted recommended measures to control its spread. Wildlife diseases continue to emerge as a consequence of globalization, and greater effort is urgently needed to protect global health.
Metalloproteinases: a Functional Pathway for Myeloid Cells
Authors: Chou Jonathan , Chan Matilda F. , Werb Zena 
Published: May 2016

ABSTRACTMyeloid cells have diverse roles in regulating immunity, inflammation, and extracellular matrix turnover. To accomplish these tasks, myeloid cells carry an arsenal of metalloproteinases, which include the matrix metalloproteinases and the adamalysins. These enzymes have diverse substrate repertoires, and are thus involved in mediating proteolytic cascades, cell migration, and cell signaling. Dysregulation of metalloproteinases contributes to pathogenic processes, including inflammation, fibrosis, and cancer. Metalloproteinases also have important nonproteolytic functions in controlling cytoskeletal dynamics during macrophage fusion and enhancing transcription to promote antiviral immunity. This review highlights the diverse contributions of metalloproteinases to myeloid cell functions.
The Phagocyte, Metchnikoff, and the Foundation of Immunology
Authors: Teti Giuseppe , Biondo Carmelo , Beninati Concetta 
Published: May 2016

ABSTRACTSince the ability of some cells to engulf particulate material was observed before Metchnikoff, he did not “discover” phagocytosis, as is sometimes mentioned in textbooks. Rather, he assigned to particle internalization the role of defending the host against noxious stimuli, which represented a new function relative to the previously recognized task of intracellular digestion. With this proposal, Metchnikoff built the conceptual framework within which immunity could finally be seen as an active host function triggered by noxious stimuli. In this sense, Metchnikoff can be rightly regarded as the father of all immunological sciences and not only of innate immunity or myeloid cell biology. Moreover, the recognition properties of his phagocyte fit surprisingly well with recent discoveries and modern models of immune sensing. For example, rather than assigning to immune recognition exclusively the function of eliminating nonself components (as others did after him), Metchnikoff viewed phagocytes as homeostatic agents capable of monitoring the internal environment and promoting tissue remodeling, thereby continuously defining the identity of the organism. No doubt, Metchnikoff’s life and creativity can provide, still today, a rich source of inspiration.
Molecular Mechanisms of Phagosome Formation
Authors: Jaumouillé Valentin , Grinstein Sergio 
Published: May 2016

ABSTRACTPhagocytosis refers to the active process that allows cells to take up large particulate material upon binding to surface receptors. The discovery of phagocytosis in 1883 by Elie Metchnikoff, leading to the concept that specialized cells are implicated in the defense against microbes, was one of the starting points of the field of immunology. After more than a century of research, phagocytosis is now appreciated to be a widely used process that enables the cellular uptake of a remarkable variety of particles, including bacteria, fungi, parasites, viruses, dead cells, and assorted debris and solid materials. Uptake of foreign particles is performed almost exclusively by specialized myeloid cells, commonly termed “professional phagocytes”: neutrophils, monocytes, macrophages, and dendritic cells. Phagocytosis of microbes not only stops or at least restricts the spread of infection but also plays an important role in regulating the innate and adaptive immune responses. Activation of the myeloid cells upon phagocytosis leads to the secretion of cytokines and chemokines that convey signals to a variety of immune cells. Moreover, foreign antigens generated by the degradation of microbes following phagocytosis are loaded onto the major histocompatibility complex for presentation to specific T lymphocytes. However, phagocytosis is not restricted to professional myeloid phagocytes; an expanding diversity of cell types appear capable of engulfing apoptotic bodies and debris, playing a critical role in tissue remodeling and in the clearance of billions of effete cells every day.
Tumor-Induced Myeloid-Derived Suppressor Cells
Authors: De Sanctis Francesco , Bronte Vincenzo , Ugel Stefano 
Published: May 2016

ABSTRACTMyeloid-derived suppressor cells (MDSCs) represent a heterogeneous, immune-suppressive leukocyte population that develops systemically and infiltrates tumors. MDSCs can restrain the immune response through different mechanisms including essential metabolite consumption, reactive oxygen and nitrogen species production, as well as display of inhibitory surface molecules that alter T-cell trafficking and viability. Moreover, MDSCs play a role in tumor progression, acting directly on tumor cells and promoting cancer stemness, angiogenesis, stroma deposition, epithelial-to-mesenchymal transition, and metastasis formation. Many biological and pharmaceutical drugs affect MDSC expansion and functions in preclinical tumor models and patients, often reversing host immune dysfunctions and allowing a more effective tumor immunotherapy.
Small RNAs in Bacterial Virulence and Communication
Authors: Svensson Sarah L. , Sharma Cynthia M. 
Published: May 2016

ABSTRACT
Bacterial pathogens must endure or adapt to different environments and stresses during transmission and infection. Posttranscriptional gene expression control by regulatory RNAs, such as small RNAs and riboswitches, is now considered central to adaptation in many bacteria, including pathogens. The study of RNA-based regulation (riboregulation) in pathogenic species has provided novel insight into how these bacteria regulate virulence gene expression. It has also uncovered diverse mechanisms by which bacterial small RNAs, in general, globally control gene expression. Riboregulators as well as their targets may also prove to be alternative targets or provide new strategies for antimicrobials. In this article, we present an overview of the general mechanisms that bacteria use to regulate with RNA, focusing on examples from pathogens. In addition, we also briefly review how deep sequencing approaches have aided in opening new perspectives in small RNA identification and the study of their functions. Finally, we discuss examples of riboregulators in two model pathogens that control virulence factor expression or survival-associated phenotypes, such as stress tolerance, biofilm formation, or cell-cell communication, to illustrate how riboregulation factors into regulatory networks in bacterial pathogens.
Epidemiology of children with head injury: a national overview
Authors: Trefan L , Houston R , Pearson G , Edwards R , Hyde P , Maconochie I , Parslow RC , Kemp A 
Published: May 2016

BackgroundThe National Confidential Enquiry describes the epidemiology of children admitted to hospital with head injury.MethodChildren (<15 years old) who died or were admitted for >4 h with head injury were identified from 216 UK hospitals (1 September 2009 to 28 February 2010). Data were collected using standard proformas and entered on to a database. A descriptive analysis of the causal mechanisms, child demographics, neurological impairment, CT findings, and outcome at 72 h are provided.ResultsDetails of 5700 children, median age 4 years (range 0–14.9 years), were analysed; 1093 (19.2%) were <1 year old, 3500 (61.4%) were boys. There was a significant association of head injury with social deprivation 39.7/100 000 (95% CI 37.0 to 42.6) in the least deprived first quintile vs. 55.1 (95% CI 52.1 to 58.2) in the most deprived fifth quintile (p<0.01). Twenty-four children died (0.4%). Most children were admitted for one night or less; 4522 (79%) had a Glasgow Coma Scale score of 15 or were Alert (on AVPU (Alert, Voice, Pain, Unresponsive)). The most common causes of head injury were falls (3537 (62.1%); children <5 years), sports-related incidents (783 (13.7%); median age 12.4 years), or motor vehicle accidents (MVAs) (401 (7.1%); primary-school-aged children). CT scans were performed in 1734 (30.4%) children; 536 (30.9%) were abnormal (skull fracture and/or intracranial injury or abnormality): 269 (7.6%) were falls, 82 (10.5%) sports related and 100 (25%). A total of 357 (6.2%) children were referred to social care because of child protection concerns (median age 9 months (range 0–14.9 years)).ConclusionsThe data described highlight priorities for targeted age-specific head injury prevention and have the potential to provide a baseline to evaluate the effects of regional trauma networks (2012) and National Institute of Health and Care Excellence (NICE) head injury guidelines (2014), which were revised after the study was completed.
A cross-sectional study of hyponatraemia among elderly patients with heart failure in Uganda
Authors: Nankabirwa Harriet , Kalyesubula Robert , Ssinabulya Isaac , Katabira Elly T , Cumming Robert G 
Published: May 2016

BackgroundHyponatraemia is a common electrolyte disturbance among older patients. We determined the prevalence of and factors associated with hyponatraemia among older patients with predominantly acute decompensated heart failure attending a tertiary hospital in Kampala, Uganda.ObjectivesMain study aim: (1) to determine the prevalence of hyponatraemia among patients aged 60 years and above with heart failure attending Mulago National Referral Hospital; (2) to describe the factors associated with hyponatraemia among patients aged 60 years and above with heart failure attending Mulago National Referral Hospital.SettingThe study was conducted in one tertiary hospital located in the northeast of Kampala, Uganda.Participants400 adults aged 60 years and above were identified for the study. Of these, 188 were excluded as they did not fulfil the inclusion criteria and one declined to participate, leaving a final study group of 211 older adults aged 60 years and above, with a clinical diagnosis of heart failure using Framingham's criteria.ResultsThe prevalence of hyponatraemia was 24.2% (51/211). Hyponatraemia was mainly found in patients with mild-to-moderate heart failure, New York Heart Association classes 2 and 3. Of the 51 patients with hyponatraemia, 27 (52.9%) had mild hyponatraemia, while 24 (47.1%) had moderate to severe hyponatraemia of 130–125 mmol/L. History of vomiting (OR=2.94, 95% CI 1.29 to 6.70, p=0.010) and use of loop diuretics (OR=2.71, 95% CI 1.13 to 6.52, p=0.026) were identified as independent factors associated with hyponatraemia among older patients with heart failure.ConclusionsOur study revealed a relatively high prevalence of hyponatraemia among older patients with mild to moderate heart failure. Patients presenting with a history of vomiting from any cause or use of loop diuretics were more likely to have hyponatraemia.
Telerehabilitation after total knee replacement in Italy: cost-effectiveness and cost-utility analysis of a mixed telerehabilitation-standard rehabilitation programme compared with usual care
Authors: Fusco Francesco , Turchetti Giuseppe 
Published: May 2016

ObjectivesTo assess cost-effectiveness and cost utility of telerehabilitation (TR) versus standard rehabilitation (SR) after total knee replacement (TKR).DesignMarkov decision modelling of cost-effectiveness and cost-utility analysis based on patient-level and secondary data sources employing Italian National Health Service (NHS; Ita-NHS) and Society perspectives.SettingPrimary care units (PCUs) in Italy.ParticipantsPatients discharged after TKR.InterventionsMixed SR-TR service (10 face-to-face sessions and 10 telesessions) versus SR (20 face-to-face sessions)Primary and secondary outcome measuresThe incremental cost per additional knee flexion range of motion (ROM) and per QALY gained by SR-TR compared with SR. Second, we considered the probability of being cost-effective and the probability of being more effective and less expensive.ResultsTR appears to be the cost-effective in the base case and in all of the considered scenarios, but is no longer more effective and less expensive if transportation costs are excluded. Comparing SR-TR with SR, the incremental cost-effectiveness ratio (ICER) adopting the Ita-NHS perspective for the base case was −€117/ROM gained. The cost-effectiveness probability for SR-TR was 0.98 (ceiling ratio: €50/ROM), while the joint probability of being more effective and less expensive was 0.87. Assuming that TR would increase health-related quality of life (HRQOL) utilities by 2.5%, the ICER adopting Ita-NHS perspective is −€960/QALY (cost-effectiveness probability: 1; ceiling ratio: €30 000/QALY). All the performed sensitivity analyses did not change the conclusions, but if transportation costs were excluded, the probability for SR-TR of being more clinically effective and less expensive reduced to 0.56.ConclusionsThe analysis suggested SR-TR to be cost-effective, even less expensive and more effective if the PCUs provide ambulance transportations. However, the uncertainty related to TR costs, HRQOL and long-term clinical outcomes raises important topics for future research, which should be addressed to confirm our estimates.Trial registration numberISRCTN45837371.
Nationwide population-based cohort study of uterine rupture in Belgium: results from the Belgian Obstetric Surveillance System
Authors: Vandenberghe G , De Blaere M , Van Leeuw V , Roelens K , Englert Y , Hanssens M , Verstraelen H 
Published: May 2016

ObjectivesWe aimed to assess the prevalence of uterine rupture in Belgium and to evaluate risk factors, management and outcomes for mother and child.DesignNationwide population-based prospective cohort study.SettingEmergency obstetric care. Participation of 97% of maternity units covering 98.6% of the deliveries in Belgium.ParticipantsAll women with uterine rupture in Belgium between January 2012 and December 2013. 8 women were excluded because data collection forms were not returned.ResultsData on 90 cases of confirmed uterine rupture were obtained, of which 73 had a previous Caesarean section (CS), representing an estimated prevalence of 3.6 (95% CI 2.9 to 4.4) per 10 000 deliveries overall and of 27 (95% CI 21 to 33) and 0.7 (95% CI 0.4 to 1.2) per 10 000 deliveries in women with and without previous CS, respectively. Rupture occurred during trial of labour after caesarean section (TOLAC) in 57 women (81.4%, 95% CI 68% to 88%), with a high rate of augmented (38.5%) and induced (29.8%) labour. All patients who underwent induction of labour had an unfavourable cervix at start of induction (Bishop Score ≤7 in 100%). Other uterine surgery was reported in the history of 22 cases (24%, 95% CI 17% to 34%), including 1 case of myomectomy, 3 cases of salpingectomy and 2 cases of hysteroscopic resection of a uterine septum. 14 cases ruptured in the absence of labour (15.6%, 95% CI 9.5% to 24.7%). No mothers died; 8 required hysterectomy (8.9%, 95% CI 4.6% to 16.6%). There were 10 perinatal deaths (perinatal mortality rate 117/1000 births, 95% CI 60 to 203) and perinatal asphyxia was observed in 29 infants (34.5%, 95% CI 25.2% to 45.1%).ConclusionsThe prevalence of uterine rupture in Belgium is similar to that in other Western countries. There is scope for improvement through the implementation of nationally adopted guidelines on TOLAC, to prevent use of unsafe procedures, and thereby reduce avoidable morbidity and mortality.
Access to primary care for socioeconomically disadvantaged older people in rural areas: a realist review
Authors: Ford John A , Wong Geoff , Jones Andy P , Steel Nick 
Published: May 2016

ObjectiveThe aim of this review is to identify and understand the contexts that effect access to high-quality primary care for socioeconomically disadvantaged older people in rural areas.DesignA realist review.Data sourcesMEDLINE and EMBASE electronic databases and grey literature (from inception to December 2014).Eligibility criteria for selecting studiesBroad inclusion criteria were used to allow articles which were not specific, but might be relevant to the population of interest to be considered. Studies meeting the inclusion criteria were assessed for rigour and relevance and coded for concepts relating to context, mechanism or outcome.AnalysisAn overarching patient pathway was generated and used as the basis to explore contexts, causal mechanisms and outcomes.Results162 articles were included. Most were from the USA or the UK, cross-sectional in design and presented subgroup data by age, rurality or deprivation. From these studies, a patient pathway was generated which included 7 steps (problem identified, decision to seek help, actively seek help, obtain appointment, get to appointment, primary care interaction and outcome). Important contexts were stoicism, education status, expectations of ageing, financial resources, understanding the healthcare system, access to suitable transport, capacity within practice, the booking system and experience of healthcare. Prominent causal mechanisms were health literacy, perceived convenience, patient empowerment and responsiveness of the practice.ConclusionsSocioeconomically disadvantaged older people in rural areas face personal, community and healthcare barriers that limit their access to primary care. Initiatives should be targeted at local contextual factors to help individuals recognise problems, feel welcome, navigate the healthcare system, book appointments easily, access appropriate transport and have sufficient time with professional staff to improve their experience of healthcare; all of which will require dedicated primary care resources.
Determinants of adherence to seasonal influenza vaccination among healthcare workers from an Italian region: results from a cross-sectional study
Authors: Durando P , Alicino C , Dini G , Barberis I , Bagnasco A M , Iudici R , Zanini M , Martini M , Toletone A , Paganino C , Massa E , Orsi A , Sasso L 
Published: May 2016

ObjectivesNotwithstanding decades of efforts to increase the uptake of seasonal influenza (flu) vaccination among European healthcare workers (HCWs), the immunisation rates are still unsatisfactory. In order to understand the reasons for the low adherence to flu vaccination, a study was carried out among HCWs of two healthcare organisations in Liguria, a region in northwest Italy.MethodsA cross-sectional study based on anonymous self-administered web questionnaires was carried out between October 2013 and February 2014. Through univariate and multivariate regression analysis, the study investigated the association between demographic and professional characteristics, knowledge, beliefs and attitudes of the study participants and (i) the seasonal flu vaccination uptake in the 2013/2014 season and (ii) the self-reported number of flu vaccination uptakes in the six consecutive seasons from 2008/2009 to 2013/2014.ResultsA total of 830 HCWs completed the survey. Factors statistically associated with flu vaccination uptake in the 2013/2014 season were: being a medical doctor and agreeing with the statements ‘flu vaccine is safe’, ‘HCWs have a higher risk of getting flu’ and ‘HCWs should receive flu vaccination every year’. A barrier to vaccination was the belief that pharmaceutical companies influence decisions about vaccination strategies.DiscussionAll the above-mentioned factors, except the last one, were (significantly) associated with the number of flu vaccination uptakes self-reported by the respondents between season 2008/2009 and season 2013/2014. Other significantly associated factors appeared to be level of education, being affected by at least one chronic disease, and agreeing with mandatory flu vaccination in healthcare settings.ConclusionsThis survey allows us to better understand the determinants of adherence to vaccination as a fundamental preventive strategy against flu among Italian HCWs. These findings should be used to improve and customise any future promotion campaigns to overcome identified barriers to immunisation.
ADA2 deficiency: case report of a new phenotype and novel mutation in two sisters
Authors: Uettwiller F , Sarrabay G , Rodero M P , Rice G I , Lagrue E , Marot Y , Deiva K , Touitou I , Crow Y J , Quartier P 
Published: May 2016

The objective of this paper is todescribe the phenotype compound heterozygote for mutations inCECR1in two children. We describe the clinical and immunological phenotype, including the assessment of ADA2 activity, cytokine expression, interferon-stimulated and neutrophil-stimulated gene signatures, and the results of CECR1 sequencing. The first patient presented with intermittent fever, cutaneous vasculitis, myalgia and muscle inflammation on MRI leading to a provisional diagnosis of periarteritis nodosa. Subsequently, two cerebral lacunar lesions were identified following a brain stroke. Clinical features improved on anti-tumour necrosis factor therapy. The first patient's sister demonstrated early-onset, long-lasting anaemia with mild biological inflammation; at the ages of 3 and 5 years, she had presented 2 acute, transient neurological events with lacunar lesions on MRI. CECR1 sequencing identified both sisters to be compound heterozygous for a p.Tyr453Cys mutation and a previously undescribed deletion of exon 7. ADA2 activity was reduced by 50%. Neutrophil-stimulated genes were not overexpressed, but interferon-stimulated genes were. The expression of a panel of other cytokine transcripts was not significantly altered. In conclusion, searching forCECR1mutation or assessing ADA2 activity should be considered in patients with an atypical presentation of inflammatory disease.