Micro-elimination of hepatitis C virus infection in the rural and remote areas of Taiwan - A multi-center collaborative care model.

INTRODUCTION: Taiwan has several hepatitis C virus (HCV) hyper-endemic areas. We aimed to evaluate the effectiveness and safety of a collaborative HCV care system with an outreach decentralized strategy among the resource-constrained rural/remote areas of Taiwan. METHODS: The pilot study was conducted in four high HCV-endemic townships in the rural/remote areas of Taoyuan, Alishan, Zhuoxi and Xiulin. Registered residents who worked or lived in the four areas and were aged 30-75 years were invited to participate in this program. Multidisciplinary HCV care teams provided outreach decentralized services of anti-HCV screening, link-to-diagnosis, and link-to-treatment with direct-acting antiviral agents (DAA). The primary end-point was sustained virological response (SVR). RESULTS: Of 8291 registered residents who were invited as the target population, 7807 (94.2%) subjects received anti-HCV screening, with the average anti-HCV prevalence rate of 14.2% (1108/7807) (range among four areas: 11.8%-16.7%). The rate of link-to-diagnosis was 94.4% (1046/1108) of anti-HCV-positive subjects (range: 90.9%-100%) with an average HCV-viremic rate of 55.1% (576/1046) (range: 50.0%-64.3%). The link-to-treat rate was 94.4% (544/576) in HCV-viremic subjects (range from 92.7% to 97.2%). Overall, 523 (96.1%) patients achieved an SVR (range: 94.7%-97.6%). Eventually, the overall effectiveness was 80.7% (range: 74.6%-93.1%). The presence of hepatocellular carcinoma at baseline was the only factor associated with DAA failure. The DAA regimens were well-tolerated. CONCLUSION: The outreach decentralized community-based care system with DAA therapy was highly effective and safe in the achievement of HCV micro-elimination in the resource-constrained rural and remote regions, which could help us to tackle the disparity.

MicroRNA 876-5p modulates EV-A71 replication through downregulation of host antiviral factors.

BACKGROUND: Human enterovirus 71 (EV-A71) is a non-enveloped virus that has a single stranded positive sense RNA genome. In a previous study, we showed that miR-876-5p upregulation was observed in the serum of patients with severe EV-A71 infection. Micro-876-5p (miR-876-5p) is a circulating miRNA that can be identified to modulate EV-A71 infections through both in vitro and in vivo studies. However, the regulatory mechanisms that involve miR-876-5p in the EV-A71 infection cycle remain unclear. METHODS: We demonstrated that miR-876-5p facilitated EV-A71 replication and expression by overexpression and knocking-down of miR-876-5p through the transfection of miR-876-5p plasmid and miR-876-5p inhibitor. Although miR-876-5p suppressed CREB5 expression, luciferase reporter assay confirmed this. We also evaluated the role of miR-876-5p in the EV-A71 infection cycle by CREB5 mediated by transfection with an anti-miR-876-5P inhibitor or in combination with an si-CREB5 plasmid. RESULTS: MicroR-876-5p was upregulated in EV-A71-infected neuroblastoma cells. Overexpression of miR-876-5p or knockdown of cyclic-AMP responsive element binding protein 5 (CREB5) promoted EV-A71 replication. The downregulation of miR-876-5p inhibited the accumulation of viral RNA and the production of viral proteins. Interestingly, CREB5 overexpression also suppressed EV-A71 replication. Our in vitro studies reveal that miR-876-5p directly targets CREB5. Finally, downregulation of CREB5 protein abated the inhibitory effect of anti-miR-876-5p and induced inhibitory effect of EV-A71 replication. CONCLUSIONS: Our results suggest that intracellular miR-876-5p promotes EV-A71 replication indirectly by targeting the host CREB5 protein.

Association between IPTA gene polymorphisms and hematological abnormalities in hepatitis C virus-infected patients receiving combination therapy.

BACKGROUND/AIMS: Hematological abnormalities during hepatitis C virus (HCV) combination therapy with pegylated interferon α and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combina-tion treatments but have also been associated with larger decreases in platelet counts. We aimed to identify the as-sociation between specific ITPA gene polymorphisms and hematological abnormalities in patients undergoing HCV combination therapy. METHODS: In this retrospective study, 175 patients treated with HCV combination therapy were enrolled at St. Martin De Porres Hospital in Taiwan between 2006 and 2012. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs1127354, rs6051702) were genotyped. We investigated the effect of ITPA gene variants on hematological abnormalities during the therapy. RESULTS: The ITPA rs1127354 minor variants were significantly associated with protection against anemia at week 4 (p=1.86×10(-6)) and with more severe decreases in platelet counts during HCV combination therapy. SNP rs6051702 was not associated with the hemoglobin decline to >3 g/dL at week 4 in our study (p=0.055). CONCLUSIONS: The ITPA SNP rs1127354 is a useful predictor of ribavirin-induced anemia in Taiwanese patients and may be related to more severe decreases in platelet counts during the early stage of HCV combination therapy. (Gut Liver, 2015;9214-223).

Preliminary results of dancing exercise on postural stability in adolescent females.

Twenty-six female student dancers of Chung-hua school of Art (mean age 17.5 ± 0.5 years) and twenty-five healthy active female collegiate students (mean age 18.1 ± 1.0 years) participated in this study to investigate the effects of dancing exercise on postural stability of adolescent female through a comparison study of two cohorts. The groups were matched in height and weight. Participants were excluded for left-side dominance, sustained lower extremity injury, any known vestibular system dysfunction, uncorrected visual problems, and other neurological conditions. Static and dynamic standing balances were measured by means of Biodex Stability System in six conditions include bilateral, dominant, and nondominant single leg stances with eye-open and eye-closed conditions. To investigate the difference between static and dynamic stabilities, two protocols were performed: the first protocol consisted of four positions including static position, Level 8, Level 4, and Level 1, respectively. They were instructed to maintain a level platform as stably as possible for a period of 30 seconds for each test and given a 30-second rest between tests. The second protocol was descending stability level that was gradually changed from Level 12 to Level 1 for 60 seconds. Balance indices included overall stability index, anterior-posterior stability index (APSI), and medial-lateral stability index. The results of first protocol showed that there were significant differences in overall stability index score between study and control groups at Level 8 with dominant single leg standing in the eye-open condition and the APSI score at Level 8 and at Level 4 with dominant single-leg standing in the eye-closed condition. There was no significant difference in the second protocol. The possible explanation is loss of familiarization adaptation because of level change consequently in both the groups, not step-by-step as in the first protocol study. Furthermore, a positive correlation was found between the dancing experience and the APSI at Level 8 and Level 4 with dominant single-leg standing in the eye-closed condition. In conclusion the findings implied that dancing exercise results in better postural stability and less visual dependence on postural control in adolescent females.

Ultrasonographic findings in hemiplegic shoulders of stroke patients.

Shoulder problems are frequently noted in hemiplegic shoulders and compromise rehabilitation. Many tools were used to evaluate the etiology of shoulder problems but most of them are either nonspecific to the evaluation of soft tissue or not convenient. In order to evaluate soft tissue and joint change in hemiplegic shoulders, 82 patients with hemiplegic shoulders caused by cerebral vascular accident (CVA) were collected and evaluated by ultrasonography with 5-12 MHz high-resolution electronic linear scanner (ATL ultrasound HDI 1500, USA). The non-hemiplegic shoulders were also studied as control group. The results showed that ultrasonographic changes were noted in 51 (62.2%) hemiplegic shoulders while changes only occurred in 17 (20.7%) non-hemiplegic shoulders. Effusion and tendinitis were the major changes showing statistical difference compared with non-hemiplegic shoulders, but there was no significant difference in the incidence of supraspinatus tendon tear between hemiplegic and non-hemiplegic shoulders. Further, the interval from the onset of CVA was not significantly correlated with the presence of positive ultrasonographic findings in hemiplegic shoulders. The results demonstrated that ultrasonography is a potential method in the evaluation of hemiplegic shoulder.