Toll-like receptor polymorphisms and cerebral malaria: <it>TLR2 </it>Δ22 polymorphism is associated with protection from cerebral malaria in a case control study

<p>Abstract</p> <p>Background</p> <p>In malaria endemic areas, host genetics influence whether a <it>Plasmodium falciparum</it>-infected child develops uncomplicated or severe malaria. TLR2 has been identified as a receptor for <it>P. falciparum</it>-derived glycosylphosphatidylinositol (GPI), and polymorphisms within the TLR2 gene may affect disease pathogenesis. There are two common polymorphisms in the 5' un-translated region (UTR) of TLR2, a 22 base pair deletion in the first unstranslated exon (Δ22), and a GT dinucleotide repeat in the second intron (GTn).</p> <p>Methods</p> <p>These polymorphisms were examined in a Ugandan case control study on children with either cerebral malaria or uncomplicated malaria. Serum cytokine levels were analysed by ELISA, according to genotype and disease status. In vitro TLR2 expression was measured according to genotype.</p> <p>Results</p> <p>Both Δ22 and GTn polymorphisms were highly frequent, but only Δ22 heterozygosity was associated with protection from cerebral malaria (OR 0.34, 95% confidence intervals 0.16, 0.73). In vitro, heterozygosity for Δ22 was associated with reduced pam3cys inducible TLR2 expression in human monocyte derived macrophages. In uncomplicated malaria patients, Δ22 homozygosity was associated with elevated serum IL-6 (<it>p </it>= 0.04), and long GT repeat alleles were associated with elevated TNF (<it>p </it>= 0.007).</p> <p>Conclusion</p> <p>Reduced inducible TLR2 expression may lead to attenuated pro-inflammatory responses, a potential mechanism of protection from cerebral malaria present in individuals heterozygous for the TLR2 Δ22 polymorphism.</p

The safety of over-the-counter niacin. A randomized placebo-controlled trial [ISRCTN18054903]

BACKGROUND: Niacin is widely available over the counter (OTC). We sought to determine the safety of 500 mg immediate release niacin, when healthy individuals use them as directed. METHODS: 51 female and 17 male healthy volunteers (mean age 27 years SD 4.4) participated in a randomized placebo-controlled blinded trial of a single dose of an OTC, immediate-release niacin 500 mg (n = 33), or a single dose of placebo (n = 35) on an empty stomach. The outcomes measured were self-reported incidence of flushing and other adverse effects. RESULTS: 33 volunteers on niacin (100%) and 1 volunteer on placebo (3%) flushed (relative risk 35, 95% confidence interval (CI) 6.8–194.7). Mean time to flushing on niacin was 18.2 min (95% CI: 12.7–23.6); mean duration of flushing was 75.4 min (95% CI: 62.5–88.2). Other adverse effects occurred commonly in the niacin group: chills (51.5% vs. 0%, P < .0001), generalized pruritus (75% vs. 0%, P = <.001), gastrointestinal upset (30% vs. 3%, P = .005), and cutaneous tingling (30% vs. 0%, P = <.001). Six participants did not tolerate the adverse effects of niacin and 3 required medical attention. CONCLUSION: Clinicians counseling patients about niacin should alert patients not only about flushing but also about gastrointestinal symptoms, the most severe in this study. They should not trust that patients would receive information about these side effects or their prevention (with aspirin) from the OTC packet insert

Aqueous extracts from dietary supplements influence the production of inflammatory cytokines in immortalized and primary T lymphocytes

<p>Abstract</p> <p>Background</p> <p>Congaplex^®and Immuplex^®are dietary supplements that have been traditionally used to support immune system function. The purpose of these experiments was to determine whether Congaplex^®and Immuplex^®affect immune function using primary and immortalized T lymphocytes.</p> <p>Methods</p> <p>Immortalized CEM and Jurkat T lymphocytes and primary peripheral mononuclear blood cells (PBMCs) were treated with the aqueous extracts from Congaplex^®and Immuplex^®to determine the effects of these products on cytokine production in activated T lymphocytes.</p> <p>Results</p> <p>Congaplex^®enhanced phytohemagglutinin/phorbol 12-myristate 13-acetate (PHA/PMA) stimulation of both CEM and Jurkat cells as measured by the production of cytokines, while Immuplex^®suppressed PHA/PMA-induced production of cytokines, with the exception of interleukin (IL)-8 which was enhanced by Immuplex^®. <it>In vitro </it>treatment of PBMCs from 10 healthy donors with Congaplex^®or Immuplex^®decreased PHA-stimulated production of interferon (IFN)-γ but increased the production of IL-13.</p> <p>Conclusions</p> <p>While the effects of Congaplex^®and Immuplex^®differed in these two models, these data demonstrate that the aqueous extracts from these two dietary supplements can affect the inflammatory response of T lymphocytes.</p

A Single Molecule Scaffold for the Maize Genome

About 85% of the maize genome consists of highly repetitive sequences that are interspersed by low-copy, gene-coding sequences. The maize community has dealt with this genomic complexity by the construction of an integrated genetic and physical map (iMap), but this resource alone was not sufficient for ensuring the quality of the current sequence build. For this purpose, we constructed a genome-wide, high-resolution optical map of the maize inbred line B73 genome containing >91,000 restriction sites (averaging 1 site/∼23 kb) accrued from mapping genomic DNA molecules. Our optical map comprises 66 contigs, averaging 31.88 Mb in size and spanning 91.5% (2,103.93 Mb/∼2,300 Mb) of the maize genome. A new algorithm was created that considered both optical map and unfinished BAC sequence data for placing 60/66 (2,032.42 Mb) optical map contigs onto the maize iMap. The alignment of optical maps against numerous data sources yielded comprehensive results that proved revealing and productive. For example, gaps were uncovered and characterized within the iMap, the FPC (fingerprinted contigs) map, and the chromosome-wide pseudomolecules. Such alignments also suggested amended placements of FPC contigs on the maize genetic map and proactively guided the assembly of chromosome-wide pseudomolecules, especially within complex genomic regions. Lastly, we think that the full integration of B73 optical maps with the maize iMap would greatly facilitate maize sequence finishing efforts that would make it a valuable reference for comparative studies among cereals, or other maize inbred lines and cultivars

Comparing T2 and T2-T3 ablation in thoracoscopic sympathectomy for palmar hyperhidrosis: A randomized control trial

10.1007/s00464-007-9241-9Surgical Endoscopy and Other Interventional Techniques21101768-177

Impact of alcohol drinking on gastric cancer development according to Helicobacter pylori infection status

BACKGROUND: Helicobacter pylori are major carcinogen of gastric cancer, but the associations among gastric cancer, H. pylori infection status, and alcohol consumption are not fully described. This study aimed to clarify how H. pylori infection status affects the association between alcohol consumption and gastric cancer risk. METHODS: We selected 949 case–cohort participants from the 18 863 Korean Multi-center Cancer Cohort (KMCC) populations. Gastric cancer incidence inside and outside of the subcohort were 12 and 254 cases, respectively. Seropositivities for CagA, VacA, and H. pylori infection were determined by performing immunoblot assays. Weighted Cox regression models were used to calculate hazard ratios and 95% confidence intervals (CIs). RESULTS: Relative to non-drinking, heavy drinking (⩾7 times a week), and binge drinking (⩾55 g alcohol intake per occasion) showed a 3.48-fold (95% CI, 1.13–10.73) and 3.27-fold (95% CI, 1.01–10.56) higher risk in subjects not previously infected by H. pylori. There was no significant association between drinking pattern and gastric cancer risk in H. pylori IgG seropositive subjects. An increased risk for gastric cancer in heavy- and binge-drinking subjects were also present in subjects not infected by CagA- or VacA-secreting H. pylori. CONCLUSIONS: Heavy and binge alcohol consumption is an important risk factor related to an increasing incidence of gastric cancer in a population not infected by H. pylori