Antiviral Activity of Compound L3 against Dengue and Zika Viruses In Vitro and In Vivo.

Dengue virus (DENV) and Zika virus (ZIKV) are mosquito-borne flaviviruses that cause severe illness after infection. Currently, there are no specific or effective treatments against DENV and ZIKV. Previous studies have shown that tyrosine kinase activities and signal transduction are involved in flavivirus replication, suggesting a potential therapeutic strategy for DENV and ZIKV. In this study, we found that compound L3 can significantly reduce viral protein expression and viral titers in HEK-293, MCF-7, HepG2, and Huh-7 cells and exhibits superior therapeutic efficacy against flaviviral infection compared to other tyrosine kinase inhibitors. In addition, compound L3 can decrease endogenous HER2 activation and inhibit the phosphorylation of the HER2 downstream signaling molecules Src and ERK1/2, the levels of which have been associated with viral protein expression in MCF-7 cells. Moreover, silencing HER2 diminished DENV-2 and ZIKV expression in MCF-7 cells, which suggests that HER2 activity is involved in flavivirus replication. Furthermore, in DENV-2-infected AG129 mice, treatment with compound L3 increased the survival rates and reduced the viremia levels. Overall, compound L3 demonstrates therapeutic efficacy both in vitro and in vivo and could be developed as a promising antiviral drug against emerging flaviviruses or for concurrent DENV and ZIKV outbreaks.

Anti-inflammatory Compound Shows Therapeutic Safety and Efficacy against Flavivirus Infection.

Flaviviruses comprise several medically important viruses, including Japanese encephalitis virus, West Nile virus, dengue virus (DENV), yellow fever virus, and Zika virus (ZIKV). A large outbreak of DENV and ZIKV occurred recently, leading to many cases of illness and death. However, despite decades of effort, we have no clinically specific therapeutic drugs against DENV and ZIKV. Previous studies showed that inflammatory responses play a critical role in dengue and Zika virus pathogenesis. Thus, in this study, we examined a series of novel anti-inflammatory compounds and found that treatment with compound 2d could dose dependently reduce viral protein expression and viral progeny production in HEK-293 and Raw264.7 cells infected with four serotypes of DENV and ZIKV. In addition, considering medication safety, compound 2d could not suppress cyclooxygenase-1 (COX-1) enzymatic activities and thus could prevent the side effect of bleeding. Moreover, compound 2d significantly inhibited COX-2 enzymatic activities and prostaglandin E2 levels, associated with viral replication, compared to results with a selective COX-2 inhibitor, celecoxib. Furthermore, administering 5 mg/kg compound 2d to DENV-2-infected AG129 mice prolonged survival and reduced viremia and serum cytokine levels. Overall, compound 2d showed therapeutic safety and efficacy in vitro and in vivo and could be further developed as a potential therapeutic agent for flavivirus infection.

Effects of malnutrition on outcomes of patients with femoral head osteonecrosis undergoing total hip arthroplasty: A population-based study.

BACKGROUND: This study aimed to evaluate the impact of malnutrition on in-hospital outcomes in patients undergoing total hip arthroplasty (THA) for osteonecrosis of the femoral head (ONFH). METHODS: This population-based retrospective study extracted data of patients undergoing THA for ONFH in the US National Inpatient Sample between 2005 and 2018. Factors associated with in-hospital mortality, medical and surgical complications, unfavorable discharge, and prolonged hospital stay were determined by logistic regression analysis. RESULTS: A total of 72,304 adults ≥18 years old with nontraumatic ONFH admitted for primary THA were included. Malnutrition was detected in 7152 (9.9%) patients using validated discharge codes. In-hospital mortality was 0.8% vs 0.1% for patients who were malnourished vs nonmalnourished. After adjusting for confounders, malnutrition was significantly associated with an increased risk of in-hospital death (adjusted odds ratio [aOR], 4.67; 95% CI, 2.43-8.97), medical complications (aOR, 1.49; 95% CI, 1.32-1.68), surgical complications (aOR, 1.78; 95% CI, 1.61-1.96), unfavorable discharge (aOR, 1.24; 95% CI, 1.11-1.39), and prolonged hospital stay (aOR, 1.90; 95% CI, 1.67-2.16) compared with adequate nutrition. Malnutrition was also associated with higher total hospital costs (adjusted ß = $9620; 95% CI, 7.87-11.36). Furthermore, the association between malnutrition, any medical or surgical complications, and unfavorable discharge was stronger in patients younger than 50 years than those ≥50 years old. CONCLUSIONS: In US patients undergoing primary THA for ONFH, malnutrition increases the risk of unfavorable in-hospital outcomes. This patient subgroup may require special attention and better strategies to improve perioperative care.

A new operative treatment for chronic biceps femoris tendon avulsion.

In this report, an original technique for augmentation of chronic biceps femoris tendon avulsion is described. The procedure is developed using a reverse fascia flap of biceps femoris to be a single-tailed graft. Then, a suture anchor is inserted on the fibular head to approximate and fix the retracted the biceps femoris. Finally, a tunnel is drilled at the proximal fibula to let the graft pass through, and the end of the graft loop is sutured to itself. This technique confers effective, firm fixation of chronic biceps femoris tendon avulsion.

Dynamic analysis and optimal design of a piezoelectric motor.

This article presents the dynamic modeling of a bimodal piezoelectric ceramic motor by use of the finite element method. The extended Hamilton's principle is utilized for formulating dynamic equation of motion, and the Lagrange multiplier method is used to model the contact dynamics between the resonator beam tip and the rotor. The numerical simulation result is approximate to the practical experimental data, which indicates that the modeling and the experiment are fairly accurate. The Taguchi experimental design method is applied to decrease the experimental effort and find the optimal design. This approach shows that the shape of the output head of the motor determines the output performance significantly. The modified shapes of output head also are carried out with a practical experiment to verify the outcomes based on the Taguchi experimental design method.

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.