Long-term impact of suboptimal rotavirus vaccines on acute gastroenteritis in hospitalized children in Northern Taiwan.

BACKGROUND/PURPOSE: Rotavirus vaccines were launched in Taiwan since early 2006. Our study was aimed to figure out long-term extended molecular epidemiology in acute gastroenteritis (AGE) in hospitalized young children after rotavirus vaccination in Taiwan. METHODS: During the 10-year period from January 2007 to December 2016, fecal samples from children under 5 years old with AGE hospitalized in Chang Gung Children's Hospital (CGCH) were examined for enteric pathogens and they were divided into two time intervals: early post-vaccine (Jan. 2007 to Dec. 2011; EPV) and late post-vaccine (Jan. 2012 to Dec. 2016; LPV). RESULTS: In total, 837 patients with AGE were enrolled with complete study. In the EPV period, 106 (26.7%) rotavirus and 65 (16.4%) norovirus infections were identified as major pathogens. In the LPV period, 79 (17.9%) rotavirus and 98 (22.2%) norovirus infections were diagnosed. Statistical analyses showed a significantly decreased prevalence of rotavirus infection (P = 0.002) and a significantly increased prevalence of norovirus (P = 0.034) and enteric bacterial infections (P < 0.001). A substantial decrease of rotavirus G1 (P = 0.079) in the LPV period and norovirus GII.4 prevailed through the decade. CONCLUSION: In Taiwan, under a suboptimal rotavirus vaccination policy, there was a marked decrease in the rate of rotavirus AGE of hospitalized young children. Significantly increased norovirus infection has replaced rotavirus as the leading cause. Expansion of rotavirus vaccine coverage, development of a norovirus prevention strategy, and sustained bacterial infection control are important for AGE containment in children in Taiwan.

Prodigiosin down-regulates survivin to facilitate paclitaxel sensitization in human breast carcinoma cell lines.

Prodigiosin is a bacterial metabolite with potent anticancer activity, which is attributed to its proapoptotic effect selectively active in malignant cells. Still, the molecular mechanisms whereby prodigiosin induces apoptosis remain largely unknown. In particular, the role of survivin, a vital inhibitor of apoptosis, in prodigiosin-induced apoptosis has never been addressed before and hence was the primary goal of this study. Our results showed that prodigiosin dose-dependently induced down-regulation of survivin in multiple breast carcinoma cell lines, including MCF-7, T-47D and MDA-MB-231. This down-regulation is mainly regulated at the level of transcription, as prodigiosin reduced the levels of both survivin mRNA and survivin promoter activity but failed to rescue survivin expression when proteasome-mediated degradation is abolished. Importantly, overexpression of survivin rendered cells more resistant to prodigiosin, indicating an essential role of survivin down-regulation in prodigiosin-induced apoptosis. In addition, we found that prodigiosin synergistically enhanced cell death induced by paclitaxel, a chemotherapy drug known to up-regulate survivin that in turn confers its own resistance. This paclitaxel sensitization effect of prodigiosin is ascribed to the lowering of survivin expression, because prodigiosin was shown to counteract survivin induction by paclitaxel and, notably, the sensitization effect was severely abrogated in cells that overexpress survivin. Taken together, our results argue that down-regulation of survivin is an integral component mediating prodigiosin-induced apoptosis in human breast cancer cells, and further suggest the potential of prodigiosin to sensitize anticancer drugs, including paclitaxel, in the treatment of breast cancer.

Early appendectomy shortens antibiotic course and hospital stay in children with early perforated appendicitis.

BACKGROUND: The optimal management of perforated appendicitis in the pediatric population has been controversial. This study aimed to compare the therapeutic efficacy between conservative treatment (CS) and early appendectomy (EA) in pediatric perforated appendicitis, and to determine whether surgical intervention is an optimal treatment modality for early perforated appendicitis in children. METHODS: Patients treated between January 2012 and April 2014, aged 0-18 years, with an imaging-based diagnosis of perforated appendicitis were retrospectively reviewed. Patients were classified into nonabscess and abscess groups by image findings, and were further categorized into CS and EA groups by treatment modality. Early perforated appendicitis was defined as having duration of symptoms≤7 days, C-reactive protein level≤200 mg/L, maximum abscess diameter≤5 cm, and absence of general peritonitis, and unstable vital signs. The clinical features and therapeutic outcomes were compared between CS and EA in each group. RESULTS: A total of 326 patients had confirmed appendicitis, including 116 patients with an image diagnosis of perforation. The CS group had a significantly longer duration of symptoms, larger abscesses, and higher serum C-reactive protein levels at presentation (all p<0.05). Patients in the EA group had a shorter antibiotic course and length of hospitalization, and a lower rate of antibiotic escalation than those in the CS group (p<0.001, p<0.001, and p<0.05, respectively). In patients with early perforated appendicitis, the CS and EA groups showed no difference in baseline disease severity. Patients in the EA group also had a shorter antibiotic course and length of hospitalization than those in the CS group (p<0.001 and p<0.001, respectively). CONCLUSION: Compared with CS, EA shortens the antibiotic course and hospital stay in pediatric early perforated appendicitis, even in the presence of small abscesses.

Enhanced undecylprodigiosin production from Serratia marcescens SS-1 by medium formulation and amino-acid supplementation.

Serratia marcescens Simon Swift-1 (SS-1) was used to produce a prodigiosin-like pigment, undecylprodigiosin (UP), known to have antitumor activities and potential as an anticancer drug. Modified media containing components of Luria-Bertani (LB) broth and selected amino acids were used to improve UP production from S. marcescens SS-1. Optimal culture conditions (e.g., temperature, pH, agitation rate) for UP production were also identified. It was found that S. marcescens SS-1 was able to produce 690 mg l-1 of UP when it was grown with 5 g l-1 yeast extract alone (YE medium) under the optimal culture conditions of 30 degrees C, 200 rpm, and pH 8. The UP production of 690 mg l-1 is nearly 23-fold of that obtained from original LB medium. Addition of amino acids containing pyrrole-like structures further enhanced UP production. Nearly 2 and 1.4 g l-1 of UP was produced when the SS-1 strain was cultivated with YE medium supplemented with proline and histidine (5 g l-1), respectively. Moreover, the addition of aspartic acid (5 g l-1) also resulted in a high UP production of 1.4 g l-1. Optimal dosages of the three amino acids were subsequently determined and the highest UP production (2.5 g l-1) was achieved with the addition of 10 g l-1 of proline. This suggests that the supplementation of amino acids related to the formation of a UP precursor (e.g., pyrrolylpyrromethene) could enhance UP production by the SS-1 strain.