A Non-coding RNA of Insect HzNV-1 Virus Establishes Latent Viral Infection through MicroRNA

Heliothis zea nudivirus-1 (HzNV-1) is an insect virus previously known as Hz-1 baculovirus. One of its major early genes, hhi1, is responsible for the establishment of productive viral infection; another gene, pag1, which expresses a non-coding RNA, is the only viral transcript detectable during viral latency. Here we showed that this non-coding RNA was further processed into at least two distinct miRNAs, which targeted and degraded hhi1 transcript. This is a result strikingly similar to a recent report that herpes simplex virus produces tightly-regulated latent specific miRNAs to silence its own key early transcripts. Nevertheless, proof for the establishment of viral latency by miRNA is still lacking. We further showed that HzNV-1 latency could be directly induced by pag1-derived miRNAs in cells infected with a pag1-deleted, latency-deficient virus. This result suggests the existence of a novel mechanism, where miRNAs can be functional for the establishment of viral latency

Spatial autocorrelation analysis of health care hotspots in Taiwan in 2006

<p>Abstract</p> <p>Background</p> <p>Spatial analytical techniques and models are often used in epidemiology to identify spatial anomalies (hotspots) in disease regions. These analytical approaches can be used to not only identify the location of such hotspots, but also their spatial patterns.</p> <p>Methods</p> <p>In this study, we utilize spatial autocorrelation methodologies, including Global Moran's I and Local Getis-Ord statistics, to describe and map spatial clusters, and areas in which these are situated, for the 20 leading causes of death in Taiwan. In addition, we use the fit to a logistic regression model to test the characteristics of similarity and dissimilarity by gender.</p> <p>Results</p> <p>Gender is compared in efforts to formulate the common spatial risk. The mean found by local spatial autocorrelation analysis is utilized to identify spatial cluster patterns. There is naturally great interest in discovering the relationship between the leading causes of death and well-documented spatial risk factors. For example, in Taiwan, we found the geographical distribution of clusters where there is a prevalence of tuberculosis to closely correspond to the location of aboriginal townships.</p> <p>Conclusions</p> <p>Cluster mapping helps to clarify issues such as the spatial aspects of both internal and external correlations for leading health care events. This is of great aid in assessing spatial risk factors, which in turn facilitates the planning of the most advantageous types of health care policies and implementation of effective health care services.</p

Relationship between the anti-inflammatory properties of salmeterol/fluticasone and the expression of CD4+CD25+Foxp3+ regulatory T cells in COPD

<p>Abstract</p> <p>Background</p> <p>Salmeterol and fluticasone combination (SFC) has anti-inflammatory effects and improves clinical symptoms in patients with chronic obstructive pulmonary disease (COPD). However, the anti-inflammatory mechanism of SFC remains unclear. In this study, we investigated the inflammatory responses of COPD, as well as the relationship of the inflammatory factors with the levels of CD4⁺CD25⁺Foxp3⁺regulatory T cells (Foxp3⁺Tregs) after SFC therapy.</p> <p>Methods</p> <p>Twenty-one patients with moderate or severe COPD received treatment with 50/500 μg of SFC twice a day for 12 weeks. Before and after treatment, the patients were evaluated using the Modified Medical Research Council (MMRC) dyspnea scale and by conducting a 6-min walk test. The number of neutrophils, monocytes and lymphocytes in induced sputum were counted. Levels of cytokines, including pre-inflammatory IL-8, TNF-α, IL-17A and cytokine IL-10, in the sputum supernatant and peripheral blood were measured by ELISA. The proportion of Foxp3⁺Tregs in the total CD4⁺T cell of the peripheral blood was determined by flow cytometry. The relationship between IL-17A levels and the percentage of Foxp3⁺Tregs was analyzed by statistical analysis.</p> <p>Results</p> <p>After treatment with SFC, the forced expiratory volume in 1 s as a percentage of predicted values (FEV1%) and the 6-min walk distance in the COPD patients significantly increased, while dyspnea scores decreased. The total number of cells, neutrophils, and the percentage of neutrophils in induced sputum reduced notably, while the proportion of monocytes was significantly increased. Levels of the inflammatory cytokines IL-8, TNF-α, and IL-17A in the sputum supernatant and in the blood were markedly lowered, while IL-10 levels were unchanged. The proportion of Foxp3⁺Tregs in the total CD4⁺T cell population in the peripheral blood was drastically higher than that before treatment. The level of IL-17A was negatively correlated with the proportion of Foxp3⁺Tregs in CD4⁺T cells.</p> <p>Conclusion</p> <p>SFC can reduce the levels of inflammatory factors and improve symptoms of COPD. The levels of inflammatory factors are associated with the variation of Foxp3⁺Tregs in COPD.</p> <p>Trial registration</p> <p>This study was registered with <url>http://www.chictr.org</url> (Chinese Clinical Trial Register) as follows: ChiCTR-TNC-10001270</p

Entry of Herpes Simplex Virus Type 1 (HSV-1) into the Distal Axons of Trigeminal Neurons Favors the Onset of Nonproductive, Silent Infection

Following productive, lytic infection in epithelia, herpes simplex virus type 1 (HSV-1) establishes a lifelong latent infection in sensory neurons that is interrupted by episodes of reactivation. In order to better understand what triggers this lytic/latent decision in neurons, we set up an organotypic model based on chicken embryonic trigeminal ganglia explants (TGEs) in a double chamber system. Adding HSV-1 to the ganglion compartment (GC) resulted in a productive infection in the explants. By contrast, selective application of the virus to distal axons led to a largely nonproductive infection that was characterized by the poor expression of lytic genes and the presence of high levels of the 2.0-kb major latency-associated transcript (LAT) RNA. Treatment of the explants with the immediate-early (IE) gene transcriptional inducer hexamethylene bisacetamide, and simultaneous co-infection of the GC with HSV-1, herpes simplex virus type 2 (HSV-2) or pseudorabies virus (PrV) helper virus significantly enhanced the ability of HSV-1 to productively infect sensory neurons upon axonal entry. Helper-virus-induced transactivation of HSV-1 IE gene expression in axonally-infected TGEs in the absence of de novo protein synthesis was dependent on the presence of functional tegument protein VP16 in HSV-1 helper virus particles. After the establishment of a LAT-positive silent infection in TGEs, HSV-1 was refractory to transactivation by superinfection of the GC with HSV-1 but not with HSV-2 and PrV helper virus. In conclusion, the site of entry appears to be a critical determinant in the lytic/latent decision in sensory neurons. HSV-1 entry into distal axons results in an insufficient transactivation of IE gene expression and favors the establishment of a nonproductive, silent infection in trigeminal neurons

Proton pump inhibitors use is associated with a lower risk of acute exacerbation and mortality in patients with coexistent COPD and GERD

Vincent Yi-Fong Su,1&ndash;3 Han-Fang Liao,4 Diahn-Warng Perng,3,5&nbsp;Yueh-Ching Chou,4,6,7 Chia-Chen Hsu,6 Chia-Lin Chou,4,6&nbsp;Yuh-Lih Chang,4,6&nbsp;Jiin-Cherng Yen,4 Tzeng-Ji Chen,3,8,9 Ting-Chun Chou4,6 1Department of Internal Medicine, Taipei City Hospital, Taipei, Taiwan; 2Institute of Clinical Medicine, 3Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 4Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan; 5Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 6Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan; 7School of Pharmacy, Taipei Medical University, Taipei, Taiwan; 8Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 9Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan Objective: The effect of antacid therapy for patients with COPD and gastroesophageal reflux disease (GERD) remains unclear.Patients and methods: This nationwide population-based study was conducted using data from Taiwan&rsquo;s National Health Insurance Research Database, and enrolled COPD patients with or without GERD. Patients with COPD who were not prescribed COPD medications were excluded. Patients with GERD who underwent upper gastrointestinal endoscopy or 24-hour pH monitoring and received at least 1 antacid were enrolled as symptomatic GERD group. The primary endpoint was acute exacerbation and mortality.Results: This study included 3,485 patients with COPD and symptomatic GERD, and 13,938 patients with COPD alone and covered 12,806.57 and 56,809.78 person-years, respectively, from 2000 to 2011. After multivariate adjustment, symptomatic GERD was associated with acute exacerbation (adjusted hazard ratio [HR]: 1.35, 95% CI: 1.23&ndash;1.48, p&lt;0.0001) and mortality (HR: 1.42, 95% CI: 1.25&ndash;1.61, p&lt;0.0001). In the COPD with symptomatic GERD group, use of proton pump inhibitors was associated with a lower risk of acute exacerbation and mortality (acute exacerbation, HR 0.31, 95% CI: 0.20&ndash;0.50, p&lt;0.0001; mortality, HR 0.36, 95% CI: 0.20&ndash;0.65, p=0.0007), whereas no significant benefit was observed for histamine2-receptor antagonists.Conclusion: Use of proton pump inhibitors was associated with a lower risk of acute exacerbation and mortality in the patients with COPD and symptomatic GERD. Keywords: GERD, COPD, acute exacerbations, deat