Differential effectiveness of berry polyphenols as anti-giardial agents

Following previous work on the anti-giardial effect of blueberry polyphenols, a range of polyphenol-rich extracts from berries and other fruits was screened for their ability to kill Giardia duodenalis, an intestinal parasite of humans. Polyphenol-rich extracts were prepared from berries using solid-phase extraction and applied to trophozoites of Giardia duodenalis grown in vitro. All berry extracts caused inhibition at 166 μg gallic acid equivalents (GAE)/ml phenol content but extracts from strawberry, arctic bramble, blackberry and cloudberry were as effective as the currently used drug, metronidazole, causing complete trophozoite mortality in vitro. Cloudberry extracts were found to be the most effective causing effectively complete trophozoite mortality at 66 μg GAE/ml. The polyphenol composition of the more effective berry extracts suggested that the presence of ellagitannins could be an important factor. However, the potency of cloudberry could be related to high ellagitannin content but also to the presence of substantial amounts of unconjugated p-coumaric acid and benzoic acid. These in vitro effects occur at concentrations easily achievable in the gut after berry ingestion and we discuss the likelihood that berry extracts could be effective anti-giardial agents in vivo

Separation of Test-Free Propositional Dynamic Logics over Context-Free Languages

For a class L of languages let PDL[L] be an extension of Propositional Dynamic Logic which allows programs to be in a language of L rather than just to be regular. If L contains a non-regular language, PDL[L] can express non-regular properties, in contrast to pure PDL. For regular, visibly pushdown and deterministic context-free languages, the separation of the respective PDLs can be proven by automata-theoretic techniques. However, these techniques introduce non-determinism on the automata side. As non-determinism is also the difference between DCFL and CFL, these techniques seem to be inappropriate to separate PDL[DCFL] from PDL[CFL]. Nevertheless, this separation is shown but for programs without test operators.Comment: In Proceedings GandALF 2011, arXiv:1106.081

Temozolomide as salvage treatment in primary brain lymphomas

Methotrexate (MTX)-based chemotherapy extends survival in patients with primary brain lymphomas, but it is not clear whether multiagent chemotherapy is superior to MTX alone. Treatment options for patients with recurrent primary brain lymphoma are limited; there is no standard second-line chemotherapy. New chemotherapeutic agents with clear activity in brain lymphoma are needed for treatment of recurrent disease. We report the results of a phase II trial assessing activity of the alkylating agent temozolomide in immunocompetent patients with recurrent primary brain lymphomas, previously treated with high-dose MTX-containing chemotherapy and/or radiotherapy. A median of two courses (range 1–12) of temozolomide 150 mg m−2 day−1, for 5 days every 4 weeks was administered to 36 patients yielding nine complete and two partial responses (response rate: 31%; 95% confidence interval 16–46%). One-year survival was 31% (95% confidence interval 16–46%). Toxicity was negligible. We conclude that temozolomide is active in recurrent primary brain lymphomas and should further be evaluated in this disease, perhaps in combination with MTX as initial treatment

Reverse and Conventional Chemical Ecology Approaches for the Development of Oviposition Attractants for Culex Mosquitoes

Synthetic mosquito oviposition attractants are sorely needed for surveillance and control programs for Culex species, which are major vectors of pathogens causing various human diseases, including filariasis, encephalitis, and West Nile encephalomyelitis. We employed novel and conventional chemical ecology approaches to identify potential attractants, which were demonstrated in field tests to be effective for monitoring populations of Cx. p. quinquefasciatus in human dwellings. Immunohistochemistry studies showed that an odorant-binding protein from this species, CquiOBP1, is expressed in trichoid sensilla on the antennae, including short, sharp-tipped trichoid sensilla type, which house an olfactory receptor neuron sensitive to a previously identified mosquito oviposition pheromone (MOP), 6-acetoxy-5-hexadecanolide. CquiOBP1 exists in monomeric and dimeric forms. Monomeric CquiOBP1 bound MOP in a pH-dependent manner, with a change in secondary structure apparently related to the loss of binding at low pH. The pheromone antipode showed higher affinity than the natural stereoisomer. By using both CquiOBP1 as a molecular target in binding assays and gas chromatography-electroantennographic detection (GC-EAD), we identified nonanal, trimethylamine (TMA), and skatole as test compounds. Extensive field evaluations in Recife, Brazil, a region with high populations of Cx. p. quinquefasciatus, showed that a combination of TMA (0.9 µg/l) and nonanal (0.15 ng/µl) is equivalent in attraction to the currently used infusion-based lure, and superior in that the offensive smell of infusions was eliminated in the newly developed synthetic mixture

HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma

Jet stream position explains regional anomalies in European beech forest productivity and tree growth.

The mechanistic pathways connecting ocean-atmosphere variability and terrestrial productivity are well-established theoretically, but remain challenging to quantify empirically. Such quantification will greatly improve the assessment and prediction of changes in terrestrial carbon sequestration in response to dynamically induced climatic extremes. The jet stream latitude (JSL) over the North Atlantic-European domain provides a synthetic and robust physical framework that integrates climate variability not accounted for by atmospheric circulation patterns alone. Surface climate impacts of north-south summer JSL displacements are not uniform across Europe, but rather create a northwestern-southeastern dipole in forest productivity and radial-growth anomalies. Summer JSL variability over the eastern North Atlantic-European domain (5-40E) exerts the strongest impact on European beech, inducing anomalies of up to 30% in modelled gross primary productivity and 50% in radial tree growth. The net effects of JSL movements on terrestrial carbon fluxes depend on forest density, carbon stocks, and productivity imbalances across biogeographic regions

HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for: 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL=1.31, 95% CI=1.06-1.60; OR MZL=1.45, 95% CI=1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL=2.10, 95% CI=1.24-3.55; OR MZL= 2.10, 95% CI=0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (p-trend<0.0001, FDR=0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes

Opening the nasal valve with external dilators reduces congestive symptoms in normal subjects

BACKGROUND: We examined whether the use of two different external nasal dilator devices influenced the size of the nasal valve area and symptoms of nasal congestion. METHODS: This was a randomized blind-allocation, open three-way crossover study of Breathe Right, Side Strip Nasal Dilators, and placebo. We studied 12 healthy subjects (10 female, 2 male; age range 26-56 years). Measures of total volume and total minimum cross-sectional area were collected. Subjective symptoms were collected using a visual analog scale and an ordinal scale. RESULTS: With both products, there was significant increase in the size of the minimum cross-sectional area compared to placebo, p = 0.004. This is supported by the decrease in the subjective reports of congestion; on the visual analog scale, compared to placebo p = 0.012 and the ordinal scale, compared to placebo, p = 0.004. CONCLUSION: Both devices significantly increase the size of the nasal valve area and reduce congestion in normal subjects.http://www.ncbi.nlm.nih.gov/pubmed/1592122

Nasal decongestants for the common cold

Copyright © 2008 The Cochrane CollaborationThe definitive version may be found at www.wiley.comBackground The common cold is a major and recurrent cause of morbidity, on average affecting children and adults two or more times each year. Nasal congestion is its commonest symptom and many therapies are marketed for its relief. There is no meta-analysis of controlled clinical trials on the effects of nasal decongestants in the common cold. Objectives To assess the efficacy of nasal decongestants at reducing the symptom of nasal congestion in adults and children with the common cold and to identify possible adverse effects associated with their use. Search strategy In this updated review in 2006, the following databases were searched: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2006); MEDLINE (January 1996 to September 2006); OLDMEDLINE (1951 to 1965); EMBASE (1980 to Week 36, 2006). We contacted known principal investigators and pharmaceutical companies. Selection criteria Randomised, placebo controlled trials of single-active oral and topical nasal decongestants in adults and children suffering from common cold. Data collection and analysis Two review authors (DT and GJL) independently extracted data. All outcomes variables were continuous. Subjective outcomes were normalised to a common scale and a weighted mean difference (WMD) was calculated. A standardised mean difference (SMD) was calculated for the objective outcomes. Main results Seven studies in adults, but none in children, fitted all inclusion criteria. There was a small but statistically significant 6% decrease in subjective symptoms after a single dose of decongestant compared with placebo. This was supported by a significant decrease in nasal airways resistance. With repeated doses, nasal decongestants produce a very small statistical benefit of 4% over three to five days, again supported by a decrease in nasal airways resistance. Two studies provided safety data for this meta-analysis, showing a relatively small number of adverse events and only a small increased risk of insomnia with pseudoephedrine compared to placebo. Authors' conclusions A single oral dose of nasal decongestant in the common cold is modestly effective for the short term relief of congestion in adults, and these drugs also provide benefit in some individuals after regular use over three to five days. Adverse events in adults are rare and mild. There is insufficient data on the use of these medications in children and therefore they are not recommended for use in children younger than 12 years of age with the common cold