instruction:
In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
question:
The lengthy duration of multidrug therapy needed to cure tuberculosis (TB) poses significant challenges for global control of the disease. Moreover, chronic inflammation associated with TB leads to pulmonary damage that can remain even after successful cure. Thus, there is a great need for the development of effective shorter drug regimens to improve clinical outcome and strengthen TB control. Host-directed therapy (HDT) is emerging as a novel adjunctive strategy to enhance the efficacy and shorten the duration of TB treatment. Previously, we showed that the administration of CC-3052, a phosphodiesterase-4 inhibitor (PDE4i), reduced the host inflammatory response during Mycobacterium tuberculosis (Mtb) infection and improved the antimicrobial efficacy of isoniazid (INH) in both the mouse and rabbit models. In the present study, we evaluated the pharmacokinetics and explored the mechanism underlying the efficacy of a more potent PDE4i, CC-11050, as adjunct to INH treatment in a mouse model of pulmonary Mtb infection. Genome-wide lung transcriptome analysis confirmed the dampening of inflammation and associated network genes that we previously reported with CC-3052. Consistent with the reduction in inflammation, a significant improvement in Mtb control and pathology was observed in the lungs of mice treated with CC-11050 plus INH, compared to INH alone. This important confirmatory study will be used to help design upcoming human clinical trials with CC-11050 as an HDT for TB treatment.
answer:
Pharmacologic inhibition of host Phosphodiesterase-4 improves isoniazid-Mediated clearance of Mycobacterium tuberculosis


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In recent years, porcine epidemic diarrhea virus (PEDv) has caused major epidemics, which has been a burden to North America's swine industry. Low infectious dose and high viability in the environment are major challenges in eradication of this virus. To further understand the viability of PEDv in the infected manure, we longitudinally monitored survivability and infectivity of PEDv in two open earthen manure storages (EMS; previously referred to as lagoon) from two different infected swine farms identified in the province of Manitoba, Canada. Our study revealed that PEDv could survive up to 9 months in the infected EMS after the initial outbreak in the farm. The viral load varied among different layers of the EMS with an average of 1.1 × 10 5 copies/ml of EMS, independent of EMS temperature and pH. In both studied EMS, the evidence of viral replication was observed through increased viral load in the later weeks of the samplings while there was no new influx of infected manure into the EMS, which was suggestive of presence of potential alternative hosts for PEDv within the EMS. Decreasing infectivity of virus over time irrespective of increased viral load suggested the possibility of PEDv evolution within the EMS and perhaps in the new host that negatively impacted virus infectivity. Viral load in the top layer of the EMS was low and mostly non-infective suggesting that environmental factors, such as UV and sunlight, could diminish the replicability and infectivity of the virus. Thus, frequent agitation of the EMS that could expose virus to UV and sunlight might be a potential strategy for reduction of PEDv load and infectivity in the infected EMS.
answer:
Monitoring Survivability and Infectivity of Porcine Epidemic Diarrhea Virus (PEDv) in the Infected On-Farm Earthen Manure Storages (EMS)


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Background: The predominant subtypes of swine influenza A virus (SIV) in Korea swine population are H1N1, H1N2, and H3N2. The viruses are genetically close to the classical U.S. H1N1 and triple-reassortant H1N2 and H3N2 viruses, respectively. Comparative pathogenesis caused by Korean H1N1, H1N2, and H3N2 SIV was evaluated in this study. Findings: The H3N2 infected pigs had severe scores of gross and histopathological lesions at post-inoculation days (PID) 2, and this then progressively decreased. Both the H1N1 and H1N2 infected pigs lacked gross lesions at PID 2, but they showed moderate to severe pneumonia on PID 4, 7 and 14. The pigs infected with H1N1 had significant scores of gross and histopathological lesions when compared with the other pigs infected with H1N2, H3N2, and mock at PID 14. Mean SIV antigen-positive scores were rarely detected for pigs infected with H1N2 and H3N2 from PID 7, whereas a significantly increased amount of viral antigens were found in the bronchioles and alveolar epithelium of the H1N1infected pigs at PID 14. Conclusions: We demonstrated that Korean SIV subtypes had different pulmonary pathologic patterns. The Korean H3N2 rapidly induced acute lung lesions such as broncho-interstitial pneumonia, while the Korean H1N1 showed longer course of infection as compared to other strains.
answer:

Comparative pathology of pigs infected with Korean H1N1, H1N2, or H3N2 swine influenza A viruses