A novel nonhuman primate model for influenza transmission

Studies of influenza transmission are necessary to predict the pandemic potential of emerging influenza viruses. Currently, both ferrets and guinea pigs are used in such studies, but these species are distantly related to humans. Nonhuman primates (NHP) share a close phylogenetic relationship with humans and may provide an enhanced means to model the virological and immunological events in influenza virus transmission. Here, for the first time, it was demonstrated that a human influenza virus isolate can productively infect and be transmitted between common marmosets (Callithrix jacchus), a New World monkey species. We inoculated four marmosets with the 2009 pandemic virus A/California/07/2009 (H1N1pdm) and housed each together with a naïve cage mate. We collected bronchoalveolar lavage and nasal wash samples from all animals at regular intervals for three weeks post-inoculation to track virus replication and sequence evolution. The unadapted 2009 H1N1pdm virus replicated to high titers in all four index animals by 1 day post-infection. Infected animals seroconverted and presented human-like symptoms including sneezing, nasal discharge, labored breathing, and lung damage. Transmission occurred in one cohabitating pair. Deep sequencing detected relatively few genetic changes in H1N1pdm viruses replicating in any infected animal. Together our data suggest that human H1N1pdm viruses require little adaptation to replicate and cause disease in marmosets, and that these viruses can be transmitted between animals. Marmosets may therefore be a viable model for studying influenza virus transmission. © 2013 Moncla et al

Cooperative secretions facilitate host range expansion in bacteria

The majority of emergent human pathogens are zoonotic in origin, that is, they can transmit to humans from other animals. Understanding the factors underlying the evolution of pathogen host range is therefore of critical importance in protecting human health. There are two main evolutionary routes to generalism: organisms can tolerate multiple environments or they can modify their environments to forms to which they are adapted. Here we use a combination of theory and a phylogenetic comparative analysis of 191 pathogenic bacterial species to show that bacteria use cooperative secretions that modify their environment to extend their host range and infect multiple host species. Our results suggest that cooperative secretions are key determinants of host range in bacteria, and that monitoring for the acquisition of secreted proteins by horizontal gene transfer can help predict emerging zoonoses

Lethality and centrality in protein networks

In this paper we present the first mathematical analysis of the protein interaction network found in the yeast, S. cerevisiae. We show that, (a) the identified protein network display a characteristic scale-free topology that demonstrate striking similarity to the inherent organization of metabolic networks in particular, and to that of robust and error-tolerant networks in general. (b) the likelihood that deletion of an individual gene product will prove lethal for the yeast cell clearly correlates with the number of interactions the protein has, meaning that highly-connected proteins are more likely to prove essential than proteins with low number of links to other proteins. These results suggest that a scale-free architecture is a generic property of cellular networks attributable to universal self-organizing principles of robust and error-tolerant networks and that will likely to represent a generic topology for protein-protein interactions.Comment: See also http:/www.nd.edu/~networks and http:/www.nd.edu/~networks/cel

Feasibility of Prehospital Teleconsultation in Acute Stroke – A Pilot Study in Clinical Routine

BACKGROUND: Inter-hospital teleconsultation improves stroke care. To transfer this concept into the emergency medical service (EMS), the feasibility and effects of prehospital teleconsultation were investigated. METHODOLOGY/PRINCIPAL FINDINGS: Teleconsultation enabling audio communication, real-time video streaming, vital data and still picture transmission was conducted between an ambulance and a teleconsultation center. Pre-notification of the hospital was carried out with a 14-item stroke history checklist via e-mail-to-fax. Beside technical assessments possible influences on prehospital and initial in-hospital time intervals, prehospital diagnostic accuracy and the transfer of stroke specific data were investigated by comparing telemedically assisted prehospital care (telemedicine group) with local regular EMS care (control group). All prehospital stroke patients over a 5-month period were included during weekdays (7.30 a.m.-4.00 p.m.). In 3 of 18 missions partial dropouts of the system occurred; neurological co-evaluation via video transmission was conducted in 12 cases. The stroke checklist was transmitted in 14 cases (78%). Telemedicine group (n = 18) vs. control group (n = 47): Prehospital time intervals were comparable, but in both groups the door to brain imaging times were longer than recommended (median 59.5 vs. 57.5 min, p = 0.6447). The prehospital stroke diagnosis was confirmed in 61% vs. 67%, p = 0.8451. Medians of 14 (IQR 9) vs. 5 (IQR 2) stroke specific items were transferred in written form to the in-hospital setting, p<0.0001. In 3 of 10 vs. 5 of 27 patients with cerebral ischemia thrombolytics were administered, p = 0.655. CONCLUSIONS: Teleconsultation was feasible but technical performance and reliability have to be improved. The approach led to better stroke specific information; however, a superiority over regular EMS care was not found and in-hospital time intervals were unacceptably long in both groups. The feasibility of prehospital tele-stroke consultation has future potential to improve emergency care especially when no highly trained personnel are on-scene. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Register (ISRCTN) ISRCTN83270177

Hepatitis B virus infected physicians and disclosure of transmission risks to patients: A critical analysis

BACKGROUND: The potential for transmission of blood-borne pathogens such as hepatitis B virus from infected healthcare workers to patients is an important and difficult issue facing healthcare policymakers internationally. Law and policy on the subject is still in its infancy, and subject to a great degree of uncertainty and controversy. Policymakers have made few recommendations regarding the specifics of practice restriction for health care workers who are hepatitis B seropositive. Generally, they have deferred this work to vaguely defined "expert panels" which will have the power to dictate the conditions under which infected health care workers may continue to practice. DISCUSSION: In this paper we use recent Canadian policy statements as a critical departure point to propose more specific recommendations regarding disclosure of transmission risks in a way that minimizes practice restriction of hepatitis B seropositive health care workers without compromising patient safety. The range of arguments proposed in the literature are critically examined from the perspective of ethical analysis. SUMMARY: A process for considering the ethical implications of the disclosure of the sero-status of health care workers is advanced that considers the varied perspectives of different stakeholders

Ross operation in children and young adults: the Alder Hey case series

BACKGROUND: The ideal prosthesis for aortic valve replacement in children and young adults has not been found yet. In recent years there has been a renewed interest in the replacement of aortic valve with the pulmonary autograft owing to its advantages of lack of anticoagulation, potential for growth and excellent haemodynamic performance. The purpose of this study was to review our institutional experience at Alder Hey hospital with the Ross procedure in children and young adults. METHODS: From November 1996 to September 2003, 38 patients (mean age, 13.1 ± 5.7 years) underwent the Ross procedure for various aortic valve diseases using the root replacement technique. Clinical and echocardiographic follow-up was performed early (within 30 days), 3 to 6 months, and yearly after surgery. Medical records of all patients were reviewed retrospectively. RESULTS: There was 1 perioperative death. The patients were followed-up for a median interval of 36 months and up to 7 years. One patient died 3 years after surgery secondary to ventricular arrhythmia with overall mortality of 5.3%. Actuarial survival at 7 years was 94 ± 2.5% and there was 100% freedom from reoperation for autograft valve dysfunction or any other cause. Balloon dilatation was required in 2 patients for pulmonary homograft stenosis. The haemodynamics at the latest follow-up were also similar to those at the time of discharge after surgery. There was no progression in the degree of aortic regurgitation for 11 patients with trivial and 3 with mild regurgitation. CONCLUSION: Our experience demonstrates that Ross operation is an attractive option for aortic valve replacement in children and young adults. Not only can the operation be accomplished with a low operative risk but the valve function stays normal over a long period of time with minimal alteration in lifestyle and no need for repeated operations to replace the valve as a result of somatic growth of the children

Correlates of mobile screen media use among children aged 0-8: Protocol for a systematic review

Background: Childhood is a crucial period for shaping healthy behaviours; however, it currently appears to be dominated by screen time. A large proportion of young children do not adhere to the screen time recommendations, with the use of mobile screen devices becoming more common than fixed screens. Existing systematic reviews on correlates of screen time have focused largely on the traditional fixed screen devices such as television. Reviews specially focused on mobile screen media are almost non-existent. This paper describes the protocol for conducting a systematic review of papers published between 2009 and 2015 to identify the correlates of mobile screen media use among children aged 0–8 years. Methods: A systematic literature search of electronic databases will be carried out using different combinations of keywords for papers published in English between January 2009 and December 2015. Additionally, a manual search of reference lists and citations will also be conducted. Papers that have examined correlates of screen time among children aged 0–8 will be included in the review. Studies must include at least one type of mobile screen media (mobile phones, electronic tablets or handheld computers) to be eligible for inclusion. This study will identify correlates of mobile screen-viewing among children in five categories: (i) child biological and demographic correlates, (ii) behavioural correlates, (iii) family biological and demographic correlates, (iv) family structure-related correlates and (v) socio-cultural and environmental correlates. PRISMA statement will be used for ensuring transparency and scientific reporting of the results.Discussion: This study will identify the correlates associated with increased mobile screen media use among young children through the systematic review of published peer-reviewed papers. This will contribute to addressing the knowledge gap in this area. The results will provide an evidence base to better understand correlates of mobile screen media use and potentially inform the development of recommendations to reduce screen time among those aged 0–8 years

Expression of the proteolysis-inducing factor core peptide mRNA is upregulated in both tumour and adjacent normal tissue in gastro-oesophageal malignancy

Gastro-oesophageal cancer is associated with a high incidence of cachexia. Proteolysis-inducing factor (PIF) has been identified as a possible cachectic factor and studies suggest that PIF is produced exclusively by tumour cells. We investigated PIF core peptide (PIF-CP) mRNA expression in tumour and benign tissue from patients with gastro-oesophageal cancer and in gastro-oesophageal biopsies for healthy volunteers. Tumour tissue and adjacent benign tissue were collected from patients with gastric and oesophageal cancer (n=46) and from benign tissue only in healthy controls (n=11). Expression of PIF-CP mRNA was quantified by real-time PCR. Clinical and pathological information along with nutritional status was collected prospectively. In the cancer patients, PIF-CP mRNA was detected in 27 (59%) tumour samples and 31 (67%) adjacent benign tissue samples. Four (36%) gastro-oesophageal biopsies from healthy controls also expressed PIF-CP mRNA. Expression was higher in tumour tissue (P=0.031) and benign tissue (P=0.022) from cancer patients compared with healthy controls. In the cancer patients, tumour and adjacent benign tissue PIF-CP mRNA concentrations were correlated with each other (P<0.0001, r=0.73) but did not correlate with weight loss or prognosis. Although PIF-CP mRNA expression is upregulated in both tumour and adjacent normal tissue in gastro-oesophageal malignancy, expression does not relate to prognosis or cachexia. Post-translational modification of PIF may be a key step in determining the biological role of PIF in the patient with advanced cancer and cachexia