Results from omic approaches in rat or mouse models exposed to inhaled crystalline silica: a systematic review.

BACKGROUND: Crystalline silica (cSiO2) is a mineral found in rocks; workers from the construction or denim industries are particularly exposed to cSiO2 through inhalation. cSiO2 inhalation increases the risk of silicosis and systemic autoimmune diseases. Inhaled cSiO2 microparticles can reach the alveoli where they induce inflammation, cell death, auto-immunity and fibrosis but the specific molecular pathways involved in these cSiO2 effects remain unclear. This systematic review aims to provide a comprehensive state of the art on omic approaches and exposure models used to study the effects of inhaled cSiO2 in mice and rats and to highlight key results from omic data in rodents also validated in human. METHODS: The protocol of systematic review follows PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Eligible articles were identified in PubMed, Embase and Web of Science. The search strategy included original articles published after 1990 and written in English which included mouse or rat models exposed to cSiO2 and utilized omic approaches to identify pathways modulated by cSiO2. Data were extracted and quality assessment was based on the SYRCLE's Risk of Bias tool for animal studies. RESULTS: Rats and male rodents were the more used models while female rodents and autoimmune prone models were less studied. Exposure of animals were both acute and chronic and the timing of outcome measurement through omics approaches were homogeneously distributed. Transcriptomic techniques were more commonly performed while proteomic, metabolomic and single-cell omic methods were less utilized. Immunity and inflammation were the main domains modified by cSiO2 exposure in lungs of mice and rats. Less than 20% of the results obtained in rodents were finally verified in humans. CONCLUSION: Omic technics offer new insights on the effects of cSiO2 exposure in mice and rats although the majority of data still need to be validated in humans. Autoimmune prone model should be better characterised and systemic effects of cSiO2 need to be further studied to better understand cSiO2-induced autoimmunity. Single-cell omics should be performed to inform on pathological processes induced by cSiO2 exposure.

Host and viral factors associated with severity of human rhinovirus-associated infant respiratory tract illness.

BACKGROUND: Risk factors for severe human rhinovirus (HRV)-associated infant illness are unknown. OBJECTIVES: We sought to examine the role of HRV infection in infant respiratory tract illness and assess viral and host risk factors for HRV-associated disease severity. METHODS: We used a prospective cohort of term, previously healthy infants enrolled during an inpatient or outpatient visit for acute upper or lower respiratory tract illness during the fall-spring months of 2004-2008. Illness severity was determined by using an ordinal bronchiolitis severity score, with higher scores indicating more severe disease. HRV was identified by means of real-time RT-PCR. The VP4/VP2 region from HRV-positive specimens was sequenced to determine species. RESULTS: Of 630 infants with bronchiolitis or upper respiratory tract illnesses (URIs), 162 (26%) had HRV infection; HRV infection was associated with 18% of cases of bronchiolitis and 47% of cases of URI. Among infants with HRV infection, 104 (64%) had HRV infection alone. Host factors associated with more severe HRV-associated illness included a maternal and family history of atopy (median score of 3.5 [interquartile range [IQR], 1.0-7.8] vs 2.0 [IQR, 1.0-5.2] and 3.5 [IQR, 1.0-7.5] vs 2.0 [IQR, 0-4.0]). In adjusted analyses maternal history of atopy conferred an increase in the risk for more severe HRV-associated bronchiolitis (odds ratio, 2.39; 95% CI, 1.14-4.99; P = .02). In a similar model maternal asthma was also associated with greater HRV-associated bronchiolitis severity (odds ratio, 2.49, 95% CI, 1.10-5.67; P = .03). Among patients with HRV infection, 35% had HRVA, 6% had HRVB, and 30% had HRVC. CONCLUSION: HRV infection was a frequent cause of bronchiolitis and URIs among previously healthy term infants requiring hospitalization or unscheduled outpatient visits. Substantial viral genetic diversity was seen among the patients with HRV infection, and predominant groups varied by season and year. Host factors, including maternal atopy, were associated with more severe infant HRV-associated illness.

A novel group of rhinoviruses is associated with asthma hospitalizations.

BACKGROUND: Although recent studies have identified new group C human rhinoviruses (HRVCs), their spectrum of pediatric disease is unknown. OBJECTIVE: We sought to determine the presentation and burden of disease caused by HRVCs among young hospitalized children. METHODS: We conducted prospective population-based surveillance in 2 US counties among children less than 5 years of age hospitalized with acute respiratory illness or fever from October 2001 through September 2003. Nasal/throat swabs were obtained and tested for HRVs, as determined by means of RT-PCR and then characterized by means of partial sequencing. RESULTS: Of 1052 children enrolled and tested during the 2-year period, 167 (16%) had HRVs detected. Of 147 samples successfully sequenced, 64 were group A HRVs, 6 were group B HRVs, and 77 were HRVCs. Children with HRVCs were significantly more likely than those with group A HRVs to have underlying high-risk conditions, such as asthma (42% vs 23%, P = .023) and to have had a discharge diagnosis of asthma (55% vs 36%, P = .022). CONCLUSIONS: Overall, HRVCs were detected in 7% of children hospitalized for fever or respiratory conditions and constituted almost half of all rhinovirus-associated hospitalizations, suggesting that this novel group causes a substantial burden of pediatric disease.

A newly emergent genotype of West Nile virus is transmitted earlier and more efficiently by Culex mosquitoes.

Studies examining the evolution of West Nile virus since its introduction into North America have identified the emergence of a new dominant genotype (WN02) that has displaced the introduced genotype (NY99). The mechanistic basis for this displacement, however, remains obscure. Although we found no detectable difference in vitro between the genotypes in either replication or fitness, there were significant differences in vivo in Culex mosquitoes. After peroral infection, the extrinsic incubation period (EIP) of the WN02 genotype was up to 4 days shorter than the EIP of the NY99 genotype; however, after intrathoracic inoculation, there was no difference in EIP between the genotypes, suggesting that differences in genotype interaction with the mosquito midgut are likely to play a role in this phenotype. These results suggest a model for the displacement of the NY99 genotype, where earlier transmission of WN02 viruses leads to higher WN02 infection rates in avian reservoir hosts.

Methods to characterize spontaneous and startle-induced locomotion in a rotenone-induced Parkinson's disease model of Drosophila.

Parkinson's disease is a neurodegenerative disorder that results from the degeneration of dopaminergic neurons in the central nervous system, primarily in the substantia nigra. The disease causes motor deficiencies, which present as rigidity, tremors and dementia in humans. Rotenone is an insecticide that causes oxidative damage by inhibiting the function of the electron transport chain in mitochondria. It is also used to model Parkinson's disease in the Drosophila. Flies have an inherent negative geotactic response, which compels them to climb upwards upon being startled. It has been established that rotenone causes early mortality and locomotion defects that disrupt the flies' ability to climb after they have been tapped downwards. However, the effect of rotenone on spontaneous movement is not well documented. This study outlines two sensitive, reproducible, and high throughput assays to characterize rotenone-induced deficiencies in short-term startle-induced locomotion and long-term spontaneous locomotion in Drosophila. These assays can be conveniently adapted to characterize other Drosophila models of locomotion defects and efficacy of therapeutic agents.

Viral etiologies of infant bronchiolitis, croup and upper respiratory illness during 4 consecutive years.

BACKGROUND: Prospective data on viral etiology and clinical characteristics of bronchiolitis and upper respiratory illness (URI) in infants are limited. METHODS: This prospective cohort enrolled previously healthy term infants during inpatient or outpatient visits for acute URI or bronchiolitis during September to May 2004 to 2008. Illness severity was determined using an ordinal bronchiolitis severity score. Common respiratory viruses were identified by real-time reverse-transcriptase polymerase chain reaction. RESULTS: Of 648 infants, 67% were enrolled during inpatient visits and 33% during outpatient visits. Seventy percent had bronchiolitis, 3% croup and 27% URI. Among infants with bronchiolitis, 76% had respiratory syncytial virus (RSV), 18% human rhinovirus (HRV), 10% influenza, 2% coronavirus, 3% human metapneumovirus and 1% parainfluenza virus. Among infants with croup, 39% had HRV, 28% parainfluenza virus, 28% RSV, 11% influenza, 6% coronavirus and none human metapneumovirus. Among infants with URI, 46% had HRV, 14% RSV, 12% influenza, 7% coronavirus, 6% parainfluenza virus and 4% human metapneumovirus. Individual viruses exhibited distinct seasonal, demographic and clinical expression. CONCLUSIONS: The most common infections among infants seeking care in unscheduled medical visits for URI or bronchiolitis were RSV and HRV. Demographic differences were observed between patients with different viruses, suggesting that host and viral factors play a role in phenotypic expression of viral illness.

Human rhinovirus C associated with wheezing in hospitalised children in the Middle East.

BACKGROUND: Few studies have investigated the disease burden and genetic diversity of human rhinoviruses (HRVs) in developing countries. OBJECTIVES: To assess the burden of HRV in Amman, Jordan, and to characterise clinical differences between HRV groups. STUDY DESIGN: We prospectively studied children <5 years, hospitalised with respiratory symptoms and/or fever in Amman, Jordan. Viruses were identified by real-time reverse transcriptase polymerase chain reaction (RT-PCR). VP4/VP2 gene sequencing was performed on HRV-positive specimens. RESULTS: Of the 728 enrolled children, 266 (37%) tested positive for picornaviruses, 240 of which were HRV. Of the HRV-positive samples, 62 (26%) were of the recently identified group HRVC, 131 (55%) were HRVA and seven (3%) were HRVB. The HRVC strains clustered into at least 19 distinct genotypes. Compared with HRVA-infected children, children with HRVC were more likely to require supplemental oxygen (63% vs. 42%, p=0.007) and, when co-infections were excluded, were more likely to have wheezing (100% vs. 82%, p=0.016). CONCLUSIONS: There is a significant burden of HRV-associated hospitalisations in young children in Jordan. Infection with the recently identified group HRVC is associated with wheezing and more severe illness.

Creation of structured documentation templates using Natural Language Processing techniques.

Structured Clinical Documentation is a fundamental component of the healthcare enterprise, linking both clinical (e.g., electronic health record, clinical decision support) and administrative functions (e.g., evaluation and management coding, billing). One of the challenges in creating good quality documentation templates has been the inability to address specialized clinical disciplines and adapt to local clinical practices. A one-size-fits-all approach leads to poor adoption and inefficiencies in the documentation process. On the other hand, the cost associated with manual generation of documentation templates is significant. Consequently there is a need for at least partial automation of the template generation process. We propose an approach and methodology for the creation of structured documentation templates for diabetes using Natural Language Processing (NLP).

Comparative evaluation of accuracy of extraction of medication information from narrative physician notes by commercial and academic natural language processing software packages.

Medication information is frequently only found in narrative physician notes. It is now possible to extract medication data from narrative documents using NLP technology. A number of commercial and academic NLP software packages can perform this function. In this paper we report the first comparative evaluation of their accuracy. Evaluation was carried out on 150 notes randomly selected from electronic medical record. NLP software results were compared to manual abstraction of medication data by two independent reviewers. Recall, precision and F-measure for identification of medication names, doses, frequencies, routes and inactive status were computed. For different data categories, recall ranged from 6.6% to 90.6%, and precision from 16.7% to 96.6%. Recall was highest for medication names and lowest for identification of inactive medications; there were no significant differences in precision between data categories. NLP software accuracy improved significantly over the last decade but further improvements are needed, particularly in analysis of complex sentences.