Follow-Up of Patients with Multidrug Resistant Tuberculosis Four Years after Standardized First-Line Drug Treatment

Background: In 2004, an anti-tuberculosis (TB) drug resistance survey in Heilongjiang province, China, enrolled 1574 (79%) new and 421 (21%) retreatment patients. Multi-drug resistant (MDR) TB was detected in 7.2% of new and 30.4% of retreatment patients. All received treatment with standardized first-line drug (FLD) regimens. Methodology/Principal Findings: We report treatment outcomes of the 2004 cohort, and long-term outcomes as assessed in the second half of 2008. The reported cure rate for MDR-TB patients was 83% (94/113) among new and 66% (85/128) among retreatment patients (P<0.001). Ten of the 241 MDR-TB patients died during treatment. Of the remaining 231, 129 (56%) could be traced in 2008. The overall recurrence rates among new and retreatment cases were 46% and 66%, respectively (P=0.03). The overall death rates among new and retreatment cases were 25% and 46%, respectively (P=0.02). Forty percent of the traced new cases and 24% of the retreatment cases were alive and without recurrent TB (P=0.01). Of the 16 patients who failed or defaulted from treatment in 2004, only two patients were not re-diagnosed with TB by 2008. Of the 111 (86%) patients with an initial successful treatment outcome 63 (57%) had developed recurrent TB, 40 (36%) had died, 27 (24%) of them died of TB. The follow-up period of four years precluded follow-up of all patients. In a highly conservative sensitivity analysis in which we assumed that all non-included patients were alive and did not have recurrent TB, the recurrence and death rate were 33% and 21%. Conclusions/Significance: Documentation of cure based on conventional smear microscopy was a poor predictor of long term outcomes. MDR-TB patients in Heilongjiang province in China had high recurrence and death rates four years after treatment with standardized FLD regimens, reinforcing the need for early diagnosis and treatment of MDR-TB, including assessment of treatment outcomes with more sensitive laboratory method

Cathelicidin-BF, a Snake Cathelicidin-Derived Antimicrobial Peptide, Could Be an Excellent Therapeutic Agent for Acne Vulgaris

Cathelicidins are a family of antimicrobial peptides acting as multifunctional effector molecules in innate immunity. Cathelicidin-BF has been purified from the snake venoms of Bungarus fasciatus and it is the first identified cathelicidin antimicrobial peptide in reptiles. In this study, cathelicidin-BF was found exerting strong antibacterial activities against Propionibacterium acnes. Its minimal inhibitory concentration against two strains of P. acnes was 4.7 µg/ml. Cathelicidin-BF also effectively killed other microorganisms including Staphylococcus epidermidis, which was possible pathogen for acne vulgaris. Cathelicidin-BF significantly inhibited pro-inflammatory factors secretion in human monocytic cells and P. acnes-induced O2.− production of human HaCaT keratinocyte cells. Observed by scanning electron microscopy, the surfaces of the treated pathogens underwent obvious morphological changes compared with the untreated controls, suggesting that this antimicrobial peptide exerts its action by disrupting membranes of microorganisms. The efficacy of cathelicidin-BF gel topical administering was evaluated in experimental mice skin colonization model. In vivo anti-inflammatory effects of cathelicidin-BF were confirmed by relieving P. acnes-induced mice ear swelling and granulomatous inflammation. The anti-inflammatory effects combined with potent antimicrobial activities and O2.− production inhibition activities of cathelicidin-BF indicate its potential as a novel therapeutic option for acne vulgaris

Decrease in the production of beta-amyloid by berberine inhibition of the expression of beta-secretase in HEK293 cells

<p>Abstract</p> <p>Background</p> <p>Berberine (BER), the major alkaloidal component of <it>Rhizoma coptidis</it>, has multiple pharmacological effects including inhibition of acetylcholinesterase, reduction of cholesterol and glucose levels, anti-inflammatory, neuroprotective and neurotrophic effects. It has also been demonstrated that BER can reduce the production of beta-amyloid_40/42, which plays a critical and primary role in the pathogenesis of Alzheimer's disease. However, the mechanism by which it accomplishes this remains unclear.</p> <p>Results</p> <p>Here, we report that BER could not only significantly decrease the production of beta-amyloid_40/42and the expression of beta-secretase (BACE), but was also able to activate the extracellular signal-regulated kinase1/2 (ERK1/2) pathway in a dose- and time-dependent manner in HEK293 cells stably transfected with APP695 containing the Swedish mutation. We also find that U0126, an antagonist of the ERK1/2 pathway, could abolish (1) the activation activity of BER on the ERK1/2 pathway and (2) the inhibition activity of BER on the production of beta-amyloid_40/42and the expression of BACE.</p> <p>Conclusion</p> <p>Our data indicate that BER decreases the production of beta-amyloid_40/42by inhibiting the expression of BACE via activation of the ERK1/2 pathway.</p

Host factors do not influence the colonization or infection by fluconazole resistant Candida species in hospitalized patients

Nosocomial yeast infections have significantly increased during the past two decades in industrialized countries, including Taiwan. This has been associated with the emergence of resistance to fluconazole and other antifungal drugs. The medical records of 88 patients, colonized or infected with Candida species, from nine of the 22 hospitals that provided clinical isolates to the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) program in 1999 were reviewed. A total of 35 patients contributed fluconazole resistant strains [minimum inhibitory concentrations (MICs) ≧ 64 mg/l], while the remaining 53 patients contributed susceptible ones (MICs ≦ 8 mg/l). Fluconazole resistance was more frequent among isolates of Candida tropicalis (46.5%) than either C. albicans (36.8%) or C. glabrata (30.8%). There was no significant difference in demographic characteristics or underlying diseases among patients contributing strains different in drug susceptibility

Use of ecstasy and other psychoactive substances among school-attending adolescents in Taiwan: national surveys 2004–2006

<p>Abstract</p> <p>Background</p> <p>With the backdrop of a global ecstasy epidemic, this study sought to examine the trend, correlates, and onset sequence of ecstasy use among adolescents in Taiwan, where a well-established gateway drug such as marijuana is much less popular.</p> <p>Methods</p> <p>A multistage probability survey of school-attending adolescents in grades 7, 9, 10, and 12, aged 11–19 years, was conducted in 2004, 2005, and 2006. A self-administered anonymous questionnaire elicited response rates ranging from 94.3% to 96.6%. The sample sizes were 18232 respondents in 2004, 17986 in 2005, and 17864 in 2006.</p> <p>Results</p> <p>In terms of lifetime prevalence and incidence, ecstasy and ketamine by and large appeared as the first and second commonly used illegal drugs, respectively, among middle (grades 7 and 9) and high school students (grades 10 and 12) during the 3-year survey period; however, this order was reversed in the middle school-aged students starting in 2006. Having sexual experience, tobacco use, and betel nut use were factors consistently associated with the onset of ecstasy use across years. The majority of ecstasy users had been involved in polydrug use, such as the use of ketamine (41.4%–53.5%), marijuana (12.7%–18.7%), and methamphetamine (4.2%–9.5%).</p> <p>Conclusion</p> <p>From 2004 to 2006, a decline was noted in the prevalence and incidence rate of ecstasy, a leading illegal drug used by school-attending adolescents in Taiwan since the early 2000s. The emerging ketamine use trend may warrant more attention in the future.</p

Burial Depth and Stolon Internode Length Independently Affect Survival of Small Clonal Fragments

Disturbance can fragment plant clones into different sizes and unstabilize soils to different degrees, so that clonal fragments of different sizes can be buried in soils at different depths. As a short-term storage organ, solon internode may help fragmented clones of stoloniferous plants to withstand deeper burial in soils. We address (1) whether burial in soils decreases survival and growth of small clonal fragments, and (2) whether increasing internode length increases survival and growth of small fragments under burial. We conducted an experiment with the stoloniferous, invasive herb Alternanthera philoxeroides, in which single-node fragments with stolon internode of 0, 2, 4 and 8 cm were buried in soils at 0, 2, 4 and 8 cm depth, respectively. Increasing burial depth significantly reduced survival of the A. philoxeroides plants and increased root to shoot ratio and total stolon length, but did not change growth measures. Increasing internode length significantly increased survival and growth measures, but there was no interaction effect with burial depth on any traits measured. These results indicate that reserves stored in stolon internodes can contribute to the fitness of the A. philoxeroides plants subject to disturbance. Although burial reduced the regeneration capacity of the A. philoxeroides plants, the species may maintain the fitness by changing biomass allocation and stolon length once it survived the burial. Such responses may play an important role for A. philoxeroides in establishment and invasiveness in frequently disturbed habitats

A Broadly Flavivirus Cross-Neutralizing Monoclonal Antibody that Recognizes a Novel Epitope within the Fusion Loop of E Protein

Flaviviruses are a group of human pathogenic, enveloped RNA viruses that includes dengue (DENV), yellow fever (YFV), West Nile (WNV), and Japanese encephalitis (JEV) viruses. Cross-reactive antibodies against Flavivirus have been described, but most of them are generally weakly neutralizing. In this study, a novel monoclonal antibody, designated mAb 2A10G6, was determined to have broad cross-reactivity with DENV 1–4, YFV, WNV, JEV, and TBEV. Phage-display biopanning and structure modeling mapped 2A10G6 to a new epitope within the highly conserved flavivirus fusion loop peptide, the 98DRXW101 motif. Moreover, in vitro and in vivo experiments demonstrated that 2A10G6 potently neutralizes DENV 1–4, YFV, and WNV and confers protection from lethal challenge with DENV 1–4 and WNV in murine model. Furthermore, functional studies revealed that 2A10G6 blocks infection at a step after viral attachment. These results define a novel broadly flavivirus cross-reactive mAb with highly neutralizing activity that can be further developed as a therapeutic agent against severe flavivirus infections in humans

The abundance and host-seeking behavior of culicine species (Diptera: Culicidae) and Anopheles sinensis in Yongcheng city, people's Republic of China

<p>Abstract</p> <p>Background</p> <p>The knowledge of mosquito species diversity and the level of anthropophily exhibited by each species in a region are of great importance to the integrated vector control. Culicine species are the primary vectors of Japanese encephalitis (JE) virus and filariasis in China. <it>Anopheles sinensis </it>plays a major role in the maintenance of <it>Plasmodium vivax </it>malaria transmission in China. The goal of this study was to compare the abundance and host-seeking behavior of culicine species and <it>An. sinensis </it>in Yongcheng city, a representative region of <it>P. vivax </it>malaria. Specifically, we wished to determine the relative attractiveness of different animal baits versus human bait to culicine species and <it>An. sinensis</it>.</p> <p>Results</p> <p><it>Culex tritaeniorhynchus </it>was the most prevalent mosquito species and <it>An. sinensis </it>was the sole potential vector of <it>P. vivax </it>malaria in Yongcheng city. There were significant differences (P < 0.01) in the abundance of both <it>An. sinensis </it>and <it>Cx. tritaeniorhynchus </it>collected in distinct baited traps. The relative attractiveness of animal versus human bait was similar towards both <it>An. sinensis </it>and <it>Cx. tritaeniorhynchus</it>. The ranking derived from the mean number of mosquitoes per bait indicated that pigs, goats and calves frequently attracted more mosquitoes than the other hosts tested (dogs, humans, and chickens). These trends were similar across all capture nights at three distinct villages. The human blood index (HBI) of female <it>An. sinensis </it>was 2.94% when computed with mixed meals while 3.70% computed with only the single meal. 19:00~21:00 was the primary peak of host-seeking female <it>An. sinensis </it>while 4:00~5:00 was the smaller peak at night. There was significant correlation between the density of female <it>An. sinensis </it>and the average relative humidity (P < 0.05) in Wangshanzhuang village.</p> <p>Conclusions</p> <p>Pigs, goats and calves were more attractive to <it>An. sinensis </it>and <it>Cx. tritaeniorhynchus </it>than dogs, humans, and chickens. Female <it>An. sinensis </it>host-seeking activity mainly occurred from 19:00 to 21:00. Thus, we propose that future vector control against <it>An. sinensis </it>and <it>Cx. tritaeniorhynchus </it>in the areas along the Huang-Huai River of central China should target the interface of human activity with domestic animals and adopt before human hosts go to bed at night.</p