Low-Pathogenic Avian Influenza Viruses in Wild House Mice

Background: Avian influenza viruses are known to productively infect a number of mammal species, several of which are commonly found on or near poultry and gamebird farms. While control of rodent species is often used to limit avian influenza virus transmission within and among outbreak sites, few studies have investigated the potential role of these species in outbreak dynamics. Methodology/Principal Findings: We trapped and sampled synanthropic mammals on a gamebird farm in Idaho, USA that had recently experienced a low pathogenic avian influenza outbreak. Six of six house mice (Mus musculus) caught on the outbreak farm were presumptively positive for antibodies to type A influenza. Consequently, we experimentally infected groups of naïve wild-caught house mice with five different low pathogenic avian influenza viruses that included three viruses derived from wild birds and two viruses derived from chickens. Virus replication was efficient in house mice inoculated with viruses derived from wild birds and more moderate for chicken-derived viruses. Mean titers (EID50 equivalents/mL) across all lung samples from seven days of sampling (three mice/day) ranged from 103.89 (H3N6) to 105.06 (H4N6) for the wild bird viruses and 102.08 (H6N2) to 102.85 (H4N8) for the chicken-derived viruses. Interestingly, multiple regression models indicated differential replication between sexes, with significantly (p\u3c0.05) higher concentrations of avian influenza RNA found in females compared with males. Conclusions/Significance: Avian influenza viruses replicated efficiently in wild-caught house mice without adaptation, indicating mice may be a risk pathway for movement of avian influenza viruses on poultry and gamebird farms. Differential virus replication between males and females warrants further investigation to determine the generality of this result in avian influenza disease dynamics

Metabolic and Functional Genomic Studies Identify Deoxythymidylate Kinase as a Target in LKB1-Mutant Lung Cancer

The LKB1/STK11 tumor suppressor encodes a serine/threonine kinase which coordinates cell growth, polarity, motility, and metabolism. In non-small cell lung cancer, LKB1 is somatically inactivated in 25-30% of cases, often concurrently with activating KRAS mutation. Here, we employed an integrative approach to define novel therapeutic targets in KRAS-driven LKB1 mutant lung cancers. High-throughput RNAi screens in lung cancer cell lines from genetically engineered mouse models driven by activated KRAS with or without coincident Lkb1 deletion led to the identification of Dtymk, encoding deoxythymidylate kinase which catalyzes dTTP biosynthesis, as synthetically lethal with Lkb1 deficiency in mouse and human lung cancer lines. Global metabolite profiling demonstrated that Lkb1-null cells had striking decreases in multiple nucleotide metabolites as compared to the Lkb1-wt cells. Thus, LKB1 mutant lung cancers have deficits in nucleotide metabolism conferring hypersensitivity to DTYMK inhibition, suggesting that DTYMK is a potential therapeutic target in this aggressive subset of tumors

Pediatric Blast Trauma: A Systematic Review and Meta-Analysis of Factors Associated with Mortality and Description of Injury Profiles

INTRODUCTION: Blast polytrauma is among the most serious mechanisms of injury confronted by medical providers. There are currently no specific studies or guidelines that define risk factors for mortality in the context of pediatric blast injuries or describe pediatric blast injury profiles. OBJECTIVE: The objectives of this study were to evaluate risk factors for pediatric mortality and to describe differences in injury profiles between explosions related to terrorism versus unrelated to terrorism within the pediatric population. METHODS: A PRISMA systematic review and meta-analysis was performed where articles published from the years 2000-2021 were extracted from PubMed. Mortality and injury profile data were extracted from articles that met inclusion criteria. A bivariant unadjusted odds ratio (OR) analysis was performed to establish protective and harmful factors associated with mortality and to describe the injury profiles of blasts related to terrorism. Statistical significance was established at P \u3c .05. RESULTS: Thirty-eight articles were included and described a total of 222,638 unique injuries. Factors associated with increased mortality included if the explosion was related to terrorism (OR = 32.73; 95% CI, 28.80-37.21; P \u3c .05) and if the explosion involved high-grade explosives utilized in the Global War on Terror ([GWOT] OR = 1.28; 95% CI, 1.04-1.44; P \u3c .05). Factors associated with decreased mortality included if the patient was resuscitated in a North Atlantic Treaty Organization (NATO)-affiliated combat trauma hospital (OR = 0.48; 95% CI, 0.37-0.62; P \u3c .05); if the explosive was fireworks (OR = 3.20×10-5; 95% CI, 2.00×10-6-5.16×10-4; P \u3c .05); and if the explosion occurred in the United States (OR = 2.40×10-5; 95% CI, 1.51×10-6-3.87×10-4; P \u3c .05). On average, victims of explosions related to terrorism were 10.30 years old (SD = 2.73) with 68.96% (SD = 17.58%) of victims reported as male. Comparison of victims of explosions related to terrorism revealed a higher incidence of thoracoabdominal trauma (30.2% versus 8.6%), similar incidence of craniocerebral trauma (39.5% versus 43.1%), and lower incidence of extremity trauma (31.8% versus 48.3%) compared to victims of explosions unrelated to terrorism. CONCLUSION: Explosions related to terrorism are associated with increased mortality and unique injury profiles compared to explosions unrelated to terrorism in the pediatric population. Such findings are important for optimizing disaster medical education of pediatric providers in preparation for and management of acute sequelae of blast injuries-terror-related and otherwise

Is Cognitive Rest Following a Head Injury Associated with Prolonged Concussion Symptoms?

Background: Recent studies have suggested that cognitive rest may not lead toward a faster recovery from acute concussions. Furthermore, the latest international consensus concussion guidelines note the appropriate amount of cognitive rest remains undetermined. Additionally, somatization has recently been shown to be a risk factor for prolonged concussion symptoms (PCS). Objective: Our objective was to determine the relationship between cognitive rest and PCS. Additionally, we sought to determine the relationship between somatization and PCS, while also considering the interaction with cognitive rest. Design/Methods: A prospective cohort study of 5-18 year olds diagnosed with an acute concussion in a tertiary care children’s hospital emergency department was conducted from January through December 2017. Participants completed the post-concussion symptom inventory (PCSI) and Children’s Somatization Inventory (CSI) at diagnosis. Emergency department provider recommendations on rest from school were collected. Follow-up calls were completed at 1 week to determine time off from school as a proxy of cognitive rest. Rest was categorically analyzed. PCSI scores were re-assessed at 4 weeks. Results: A total of 89 patients have been enrolled with a median age of 10.0 (IQR: 8.5-13.0). 58% (N=52) of the patients are male. 82.0% (N=73) completed 7-day follow-up. 24.7% (N=18) of patients took no time off from school; 42.5% (N=31) took 1-2 days off; and 32.9% (N=24) took 3 or more days off from school. 24% had prolonged concussion symptoms. Logistic regression analysis was used to compare the rest tertiles to PCS, with no time off as the reference category. When compared to the shortest rest tertile, the longest rest tertile had a 1.35 fold increase in prolonged concussion symptoms, which was not statistically significant (95% CI: 0.31 – 5.91). When compared to the shortest rest tertile, the medium rest tertile had a 0.50 fold decrease in prolonged concussion symptoms, which was also not statistically significant (95% CI: 0.10 – 2.42). In the longer rest tertiles, somatization scores trended higher in the group with PCS (p = 0.15). Conclusion(s): In our preliminary pilot data, patients who took more time off from school did not show decreased likelihood of prolonged concussion symptoms. Furthermore, patients with somatization may be at particular risk of rest associated with prolonged concussion symptoms. Further larger scale studies, including randomized trials, are necessary to determine the risk of rest on prolonged concussion symptoms

Avian influenza A virus susceptibility, infection, transmission, and antibody kinetics in European starlings

Avian influenza A viruses (IAVs) pose risks to public, agricultural, and wildlife health. Bridge hosts are spillover hosts that share habitat with both maintenance hosts (e.g., mallards) and target hosts (e.g., poultry). We conducted a comprehensive assessment of European starlings (Sturnus vulgaris), a common visitor to both urban and agricultural environments, to assess whether this species might act as a potential maintenance or bridge host for IAVs. First, we experimentally inoculated starlings with a wild bird IAV to investigate susceptibility and replication kinetics. Next, we evaluated whether IAV might spill over to starlings from sharing resources with a widespread IAV reservoir host. We accomplished this using a specially designed transmission cage to simulate natural environmental transmission by exposing starlings to water shared with IAV-infected mallards (Anas platyrhynchos). We then conducted a contact study to assess intraspecies transmission between starlings. In the initial experimental infection study, all inoculated starlings shed viral RNA and seroconverted. All starlings in the transmission study became infected and shed RNA at similar levels. All but one of these birds seroconverted, but detectable antibodies were relatively transient, falling to negative levels in a majority of birds by 59 days post contact. None of the contact starlings in the intraspecies transmission experiment became infected. In summary, we demonstrated that starlings may have the potential to act as IAV bridge hosts if they share water with IAV-infected waterfowl. However, starlings are unlikely to act as maintenance hosts due to limited, if any, intraspecies transmission. In addition, starlings have a relatively brief antibody response which should be considered when interpreting serology from field samples. Further study is needed to evaluate the potential for transmission from starlings to poultry, a possibility enhanced by starling\u27s behavioral trait of forming very large flocks which can descend on poultry facilities when natural resources are scarce. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

History of Somatization Is Associated with Prolonged Recovery from Concussion.

OBJECTIVE: To determine the association between a history of somatization and prolonged concussion symptoms, including sex differences in recovery. STUDY DESIGN: A prospective cohort study of 10–18 year olds with an acute concussion was conducted from July 2014 to April 2015 at a tertiary care pediatric emergency department. 120 subjects completed the validated Children’s Somatization Inventory (CSI) for pre-injury somatization assessment and Post-Concussion Symptoms Score (PCSS) at diagnosis. PCSS was re-assessed by phone at 2- and 4-weeks. CSI was assessed in quartiles with a generalized estimating equation model to determine relationship of CSI to PCSS over time. RESULTS: The median age of our study participants was 13.8 years (interquartile range: 11.5, 15.8), 60% male, with analyses carried out separately for each sex. Our model showed a positive interaction between total CSI score, PCSS and time from concussion for females p < 0.01, and a statistical trend for males, p = 0.058. Females in the highest quartile of somatization had higher PCSS than the other three CSI quartiles at each time point (B −26.7 to −41.1, p-values < 0.015). CONCLUSIONS: Patients with higher pre-injury somatization had higher concussion symptom scores over time. Females in the highest somatization quartile had prolonged concussion recovery with persistently high symptom scores at 4 weeks. Somatization may contribute to sex differences in recovery, and assessment at the time of concussion may help guide management and target therapy