The Primary Resistance of Helicobacter pylori in Taiwan after the National Policy to Restrict Antibiotic Consumption and Its Relation to Virulence Factors—A Nationwide Study

Objective

The Taiwan Government issued a policy to restrict antimicrobial usage since 2001. We aimed to assess the changes in the antibiotic consumption and the primary resistance of H. pylori after this policy and the impact of virulence factors on resistance.

Methods

The defined daily dose (DDD) of antibiotics was analyzed using the Taiwan National Health Insurance (NHI) research database. H. pylori strains isolated from treatment naïve (N=1395) and failure from prior eradication therapies (N=360) from 9 hospitals between 2000 and 2012 were used for analysis. The minimum inhibitory concentration was determined by agar dilution test. Genotyping for CagA and VacA was determined by PCR method.

Results

The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997 to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to 0.35 in 2008. The primary resistance of amoxicillin, clarithromycin, metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9% respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000–2007 to 8.3% in 2008–2010 and 13.4% in 2011–2012 (p=0.001). The primary resistance of metronidazole was higher in females than males (33.1% vs. 18.8%, p<0.001), which was probably attributed to the higher consumption of nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance.

Conclusions

The low primary clarithromycin and metronidazole resistance of H. pylori in Taiwan might be attributed to the reduced consumption of macrolides and nitroimidazole after the national policy to restrict antimicrobial usage. Yet, further strategies are needed to restrict the consumption of fluoroquinolones in the face of rising levofloxacin resistance.     

Spike timing in the mammalian visual system.

Evidence is accumulating for the existence of mechanisms that create and detect synchrony among action potentials on short time scales both within and between neurons. Progress is most rapid in the retina, the lateral geniculate nucleus, and cortical slices, where signal flow is better understood or more manipulable. The debate over the functional relevance of spike timing in cortex has gained substance from new computational models but remains unresolved.     

Prokaryotic communities of the north-eastern Mongolian soda lakes

We have studied the activity and composition of several geochemically significant physiological groups of bacteria in more than twenty alkaline salt lakes of the north-east Mongolia steppe with water salinity from 3 to 390 g l^?1 and pH values ranging from 9.0 to 10.6. Active and diverse microbial communities have been found in most of the lakes. The methanotrophic bacteria were represented by the Type I members. Among the culturable forms of sulfur-oxidizing bacteria obligately chemolithoautotrophic and haloalkaliphilic representatives of the genera Thioalkalimicrobium and Thioalkalivibrio were detected in the sediments at high numbers (up to 10⁶ cells ml^?1). The largest population of anaerobic phototrophic bacteria was represented by purple sulfur bacteria of the Ectothiorhodospiraceae family. Salinity was the key factor in determining the activity and the composition of the microbial communities. The most diverse and active prokaryotic populations, including aerobic and anaerobic phototrophic, methanogenic, methanotrophic, sulfur-oxidizing, sulfate-reducing and nitrifying bacteria, were found in lakes with salinity less than 60 g l^?1. In hypersaline lakes with a salinity >100 g l^?1, the sulfur cycle remained active due to the activity of extremely halotolerant and alkaliphilic sulfur bacteria, while other important functional groups responsible for nitrification and methane oxidation processes were not detected. Overall, the prokaryotic communities of the Mongolian alkaline salt lakes represent an interesting new example of a diverse community of haloalkaliphilic bacteria well adopted to a broad salinity range.     

Carbon and nitrogen content based estimation of the fat content of animal carcasses in various species

The objective of this study was to explore whether the C and N content can be used to estimate the fat content of animal carcasses. Considering the mean C and N contents of body fat and body protein, the fat content (EE) [%] can be predicted from C and N values [%] according to the generally valid equation EE=1.3038·C – 4.237·N. The application of this equation to estimate the total fat content of all animal carcasses results in significant differences in fat content between predicted and measured values. Therefore, we derived specific equations for rats, pigs, cattle, sheep, broilers and mice to predict the fat content by dual linear regression analysis (y=EE [% DM], x₁=C [% DM], x₂=N [% DM]) based on measured fat, C, and N contents of animal body samples. The specific equations for different animals showed residual standard deviations of 1.55, 1.63, 1.12, 1.35, 1.85 and 0.92% fat for rats, pigs, cattle, sheep, broilers and mice, respectively.     

The nuclear membrane leukotriene synthetic complex is a signal integrator and transducer

Leukotrienes (LTs) are lipid-signaling molecules derived from arachidonic acid (AA) that initiate and amplify inflammation. To initiate LT formation, the 5-lipoxygenase (5-LO) enzyme translocates to nuclear membranes, where it associates with its scaffold protein, 5-lipoxygenase–activating protein (FLAP), to form the core of the multiprotein LT synthetic complex. FLAP is considered to function by binding free AA and facilitating its use as a substrate by 5-LO to form the initial LT, LTA₄. We used a combination of fluorescence lifetime imaging microscopy, cell biology, and biochemistry to identify discrete AA-dependent and AA-independent steps that occur on nuclear membranes to control the assembly of the LT synthetic complex in polymorphonuclear leukocytes. The association of AA with FLAP changes the configuration of the scaffold protein, enhances recruitment of membrane-associated 5-LO to form complexes with FLAP, and controls the closeness of this association. Granulocyte monocyte colony–stimulating factor provides a second AA-independent signal that controls the closeness of 5-LO and FLAP within complexes but not the number of complexes that are assembled. Our results demonstrate that the LT synthetic complex is a signal integrator that transduces extracellular signals to modulate the interaction of 5-LO and FLAP.     

Discovery and optimization of novel piperazines as potent inhibitors of fatty acid synthase (FASN)

The discovery, structure-activity relationships, and optimization of a novel class of fatty acid synthase (FASN) inhibitors is reported. High throughput screening identified a series of substituted piperazines with structural features that enable interactions with many of the potency-driving regions of the FASN KR domain binding site. Derived from this series was FT113, a compound with potent biochemical and cellular activity, which translated into excellent activity in in vivo models.