Association of Alpha B-Crystallin Genotypes with Oral Cancer Susceptibility, Survival, and Recurrence in Taiwan

BACKGROUND: Alpha B-crystallin (CRYAB) is a protein that functions as "molecular chaperone" in preserving intracellular architecture and cell membrane. Also, CRYAB is highly antiapoptotic. Abnormal CRYAB expression is a prognostic biomarker for oral cancer, while its genomic variations and the association with carcinogenesis have never been studied. METHODOLOGY/FINDING: Therefore, we hypothesized that CRYAB single nucleotide polymorphisms may be associated with oral cancer risk. In this hospital-based study, the association of CRYAB A-1215G (rs2228387), C-802G (rs14133) and intron2 (rs2070894) polymorphisms with oral cancer in a Taiwan population was investigated. In total, 496 oral cancer patients and 992 age- and gender-matched healthy controls were genotyped and analyzed. A significantly different frequency distribution was found in CRYAB C-802G genotypes, but not in A-1215G and intron2 genotypes, between the oral cancer and control groups. The CRYAB C-802G G allele conferred an increased risk of oral cancer (P = 1.49×10(-5)). Patients carrying CG/GG at CRYAB C-802G were of lower 5-year survival and higher recurrence rate than those of CC (P<0.05). CONCLUSION/SIGNIFICANCE: Our results provide the first evidence that the G allele of CRYAB C-802G is correlated with oral cancer risk and this polymorphism may be a useful marker for oral cancer recurrence and survival prediction for clinical reference

A systematic review of randomised controlled trials on the effectiveness of exercise programs on lumbo pelvic pain among postnatal women

Background: A substantial number of women tend to be affected by Lumbo Pelvic Pain (LPP) following child birth. Physical exercise is indicated as a beneficial method to relieve LPP, but individual studies appear to suggest mixed findings about its effectiveness. This systematic review aimed to synthesise evidence from randomised controlled trials on the effectiveness of exercise on LPP among postnatal women to inform policy, practice and future research. Methods: A systematic review was conducted of all randomised controlled trials published between January 1990 and July 2014, identified through a comprehensive search of following databases: PubMed, PEDro, Embase, Cinahl, Medline, SPORTDiscus, Cochrane Pregnancy and Childbirth Group’s Trials Register, and electronic libraries of authors’institutions. Randomised controlled trials were eligible for inclusion if the intervention comprised of postnatal exercise for women with LPP onset during pregnancy or within 3 months after delivery and the outcome measures included changes in LPP. Selected articles were assessed using the PEDro Scale for methodological quality and findings were synthesised narratively as meta-analysis was found to be inappropriate due to heterogeneity among included studies. Results: Four randomised controlled trials were included, involving 251 postnatal women. Three trials were rated as of ‘good’ methodological quality. All trials, except one, were at low risk of bias. The trials included physical exercise programs with varying components, differing modes of delivery, follow up times and outcome measures. Intervention in one trial, involving physical therapy with specific stabilising exercises, proved to be effective in reducing LPP intensity. An improvement in gluteal pain on the right side was reported in another trial and a significant difference in pain frequency in another. Conclusion: Our review indicates that only few randomised controlled trials have evaluated the effectiveness of exercise on LPP among postnatal women. There is also a great amount of variability across existing trials in the components of exercise programs, modes of delivery, follow up times and outcome measures. While there is some evidence to indicate the effectiveness of exercise for relieving LPP, further good quality trials are needed to ascertain the most effective elements of postnatal exercise programs suited for LPP treatment

Comparative Field Evaluation of Combinations of Long-Lasting Insecticide Treated Nets and Indoor Residual Spraying, Relative to Either Method Alone, for Malaria Prevention in an Area where the main Vector is Anopheles Arabiensis.

Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are commonly used together in the same households to improve malaria control despite inconsistent evidence on whether such combinations actually offer better protection than nets alone or IRS alone. Comparative tests were conducted using experimental huts fitted with LLINs, untreated nets, IRS plus untreated nets, or combinations of LLINs and IRS, in an area where Anopheles arabiensis is the predominant malaria vector species. Three LLIN types, Olyset®, PermaNet 2.0® and Icon Life® nets and three IRS treatments, pirimiphos-methyl, DDT, and lambda cyhalothrin, were used singly or in combinations. We compared, number of mosquitoes entering huts, proportion and number killed, proportions prevented from blood-feeding, time when mosquitoes exited the huts, and proportions caught exiting. The tests were done for four months in dry season and another six months in wet season, each time using new intact nets. All the net types, used with or without IRS, prevented >99% of indoor mosquito bites. Adding PermaNet 2.0® and Icon Life®, but not Olyset® nets into huts with any IRS increased mortality of malaria vectors relative to IRS alone. However, of all IRS treatments, only pirimiphos-methyl significantly increased vector mortality relative to LLINs alone, though this increase was modest. Overall, median mortality of An. arabiensis caught in huts with any of the treatments did not exceed 29%. No treatment reduced entry of the vectors into huts, except for marginal reductions due to PermaNet 2.0® nets and DDT. More than 95% of all mosquitoes were caught in exit traps rather than inside huts. Where the main malaria vector is An. arabiensis, adding IRS into houses with intact pyrethroid LLINs does not enhance house-hold level protection except where the IRS employs non-pyrethroid insecticides such as pirimiphos-methyl, which can confer modest enhancements. In contrast, adding intact bednets onto IRS enhances protection by preventing mosquito blood-feeding (even if the nets are non-insecticidal) and by slightly increasing mosquito mortality (in case of LLINs). The primary mode of action of intact LLINs against An. arabiensis is clearly bite prevention rather than insecticidal activity. Therefore, where resources are limited, priority should be to ensure that everyone at risk consistently uses LLINs and that the nets are regularly replaced before being excessively torn. Measures that maximize bite prevention (e.g. proper net sizes to effectively cover sleeping spaces, stronger net fibres that resist tears and burns and net use practices that preserve net longevity), should be emphasized

Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population

BACKGROUND: Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes. OBJECTIVES: We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures. METHODS: For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV(1)), FEV(1) over forced vital capacity (FEV(1)/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF(25-75)) was regressed on interval exposure to particulate matter >10 microm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (p(interaction)>0.05). Replication was attempted for SNPs with MAF<10% in 3320 SAPALDIA participants without GWAS. RESULTS: On the SNP-level, rs2035268 in gene SNCA accelerated FEV(1)/FVC decline by 3.8% (p(interaction) = 2.5x10(-6)), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml p(interaction) = 9.7x10(-8)) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (p(interaction) = 3.0x10(-4)) on FEV(1)/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful. CONCLUSIONS: Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobac smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challengin

Genetic and Mechanistic Evaluation for the Mixed-Field Agglutination in B3 Blood Type with IVS3+5G>A ABO Gene Mutation

Background: The ABO blood type B3 is the most common B subtype in the Chinese population with a frequency of 1/900. Although IVS3+5G.A (rs55852701) mutation of B gene has been shown to associate with the development of B3 blood type, genetic and mechanistic evaluation for the unique mixed-field agglutination phenotype has not yet been completely addressed. Methodology/Principal Findings: In this study, we analyzed 16 cases of confirmed B3 individuals and found that IVS3+5G.A attributes to all cases of B3. RT-PCR analyses revealed the presence of at least 7 types of aberrant B3 splicing transcripts with most of the transcripts causing early termination and producing non-functional protein during translation. The splicing transcript without exon 3 that was predicted to generate functional B3 glycosyltransferase lacking 19 amino acids at the N-terminal segment constituted only 0.9 % of the splicing transcripts. Expression of the B3 cDNA with exon 3 deletion in the K562 erythroleukemia cells revealed that the B3 glycosyltransferase had only 40 % of B1 activity in converting H antigen to B antigen. Notably, the typical mixed-field agglutination of B3-RBCs can be mimicked by adding anti-B antibody to the K562-B3 cells. Conclusions/Significance: This study thereby demonstrates that both aberrant splicing of B transcripts and the reduced B3 glycosyltransferase activity contribute to weak B expression and the mixed-field agglutination of B3, adding to th

Laboratory layered latte

Inducing thermal gradients in fluid systems with initial, well-defined density gradients results in the formation of distinct layered patterns, such as those observed in the ocean due to double-diffusive convection. In contrast, layered composite fluids are sometimes observed in confined systems of rather chaotic initial states, for example, lattes formed by pouring espresso into a glass of warm milk. Here, we report controlled experiments injecting a fluid into a miscible phase and show that, above a critical injection velocity, layering emerges over a time scale of minutes. We identify critical conditions to produce the layering, and relate the results quantitatively to double-diffusive convection. Based on this understanding, we show how to employ this single-step process to produce layered structures in soft materials, where the local elastic properties vary step-wise along the length of the material

Functionalization of Carbon Nanomaterial Surface by Doxorubicin and Antibodies to Tumor Markers

The actual task of oncology is effective treatment of cancer while causing a minimum harm to the patient. The appearance of polymer nanomaterials and technologies launched new applications and approaches of delivery and release of anticancer drugs. The goal of work was to test ultra dispersed diamonds (UDDs) and onion-like carbon (OLCs) as new vehicles for delivery of antitumor drug (doxorubicin (DOX)) and specific antibodies to tumor receptors. Stable compounds of UDDs and OLCs with DOX were obtained. As results of work, an effectiveness of functionalization was 2.94 % w/w for OLC-DOX and 2.98 % w/w for UDD-DOX. Also, there was demonstrated that UDD-DOX and OLC-DOX constructs had dose-dependent cytotoxic effect on tumor cells in the presence of trypsin. The survival of adenocarcinoma cells reduced from 52 to 28 % in case of incubation with the UDD-DOX in concentrations from 8.4–2.5 to 670–20 μg/ml and from 72 to 30 % after incubation with OLC-DOX. Simultaneously, antibodies to epidermal growth factor maintained 75 % of the functional activity and specificity after matrix-assisted pulsed laser evaporation deposition. Thus, the conclusion has been made about the prospects of selected new methods and approaches for creating an antitumor agent with capabilities targeted delivery of drugs

Dietary carotenoid-rich oil supplementation improves exercise-induced anisocytosis in runners: influences of haptoglobin, MnSOD (Val9Ala), CAT (21A/T) and GPX1 (Pro198Leu) gene polymorphisms in dilutional pseudoanemia (sports anemia)

Physical training induces beneficial adaptation, whereas exhaustive exercises increase reactive oxygen-species generation, thereby causing oxidative damage in plasma and erythrocytes, fractions susceptible to lipid peroxidation. Pequi (Caryocar brasiliense Camb.) is a Brazilian Cerrado fruit containing a carotenoid-rich oil. The aim was to investigate the effects of pequi-oil on exercise-induced oxidative damage in plasma and erythrocytes, after running in the same environment and undergoing weekly training under the same conditions as to type, intensity and length. Evaluations were accomplished after outdoor running on flat land before and after ingestion of 400 mg pequi-oil capsules for 14 days. Blood samples were taken after running and submitted to TBARS assay and erythrogram analysis. Haptoglobin, MnSOD (Val9Ala), CAT (21A/T) and GPX1 (Pro198Leu) gene polymorphisms were priorly investigated, so as to estimate genetic influence The reduction in erythrocytes, hemoglobin and hematocrit after pequi-oil treatment was notably associated with higher plasma expansion. Except for MCHC (mean corpuscular hemoglobin concentration) and RDW (red cell distribution width), the results were influenced by the polymorphisms studied. The best response to pequi-oil was presented by MnSOD Val/Val, CAT AA or AT genotypes and the GPX1 Pro allele. The significantly lower RDW and higher MHCH values were related to pequi-oil protective effects. Pequi oil, besides possessing other nutritional properties, showed protective blood effects

Long-Lasting Control of Anopheles arabiensis by a Single Spray Application of Micro-encapsulated Pirimiphos-methyl (Actellic(R) 300 CS).

Pyrethroid-resistant mosquitoes are an increasing threat to malaria vector control. The Global Plan for Insecticide Resistance Management (GPIRM) recommends rotation of non-pyrethroid insecticides for indoor residual spraying (IRS). The options from other classes are limited. The carbamate bendiocarb and the organophosphate pirimiphos-methyl (p-methyl) emulsifiable concentrate (EC) have a short residual duration of action, resulting in increased costs due to multiple spray cycles, and user fatigue. Encapsulation (CS) technology was used to extend the residual performance of p-methyl. Two novel p-methyl CS formulations were evaluated alongside the existing EC in laboratory bioassays and experimental hut trials in Tanzania between 2008-2010. Bioassays were carried out monthly on sprayed substrates of mud, concrete, plywood, and palm thatch to assess residual activity. Experimental huts were used to assess efficacy against wild free-flying Anopheles arabiensis, in terms of insecticide-induced mortality and blood-feeding inhibition. In laboratory bioassays of An. arabiensis and Culex quinquefasciatus both CS formulations produced high rates of mortality for significantly longer than the EC formulation on all substrates. On mud, the best performing CS killed >80% of An. arabiensis for five months and >50% for eight months, compared with one and two months, respectively, for the EC. In monthly bioassays of experimental hut walls the EC was ineffective shortly after spraying, while the best CS formulation killed more than 80% of An. arabiensis for five months on mud, and seven months on concrete. In experimental huts both CS and EC formulations killed high proportions of free-flying wild An. arabiensis for up to 12 months after spraying. There was no significant difference between treatments. All treatments provided considerable personal protection, with blood-feeding inhibition ranging from 9-49% over time. The long residual performance of p-methyl CS was consistent in bioassays and experimental huts. The CS outperformed the EC in laboratory and hut bioassays but the EC longevity in huts was unexpected. Long-lasting p-methyl CS formulations should be more effective than both p-methyl EC and bendiocarb considering a single spray could be sufficient for annual malaria control. IRS with p-methyl 300 CS is a timely addition to the limited portfolio of long-lasting residual insecticides