Online information on mandibular advancement device for the treatment of obstructive sleep apnea: A content, quality and readability analysis.

BACKGROUND: Despite increasing scientific interest in the effectiveness of mandibular advancement device (MAD) for the treatment of obstructive sleep apnoea (OSA), laypeople lack knowledge about this treatment option. OBJECTIVES: To investigate content, quality and readability of the online information regarding MAD. METHODS: Google, Yahoo and Bing were searched for 'sleep apnea', 'mandibular advancement device' and 'oral appliance'. Websites were analysed for content (multidisciplinary care team, qualified dentist, treatment contraindications and side effects), as well as for quality (DISCERN instrument, HONcode) and readability scores (Flesch Reading Ease, FRE and Flesch-Kincaid Reading Grade, FKG). RESULTS: Totally, 155 websites were included: 53% from health professionals, 20% commercial, 17% academic and 10% from non-health professionals. Content was incomplete, especially for commercial ones. 71.61% websites failed to acknowledge treatment contraindications, approximately 40.00% did not mention side effects and the need for a multidisciplinary care team, while 22.58% did not address the need to consult a qualified dentist. Quality and reliability were poor. Mean DISCERN score was 39.93 (95% CI 37.90-41.96), with lower scores for commercial websites compared with others. Only nine websites displayed HONcode certification. Readability was quite difficult, with mean FRE score of 59.50 (95% CI 57.58-61.42) and mean FKG level of 6.92 (95% CI 6.64-7.21). CONCLUSION: Health care professionals should be aware that currently available online information do not fulfil the most important aspects of MAD therapy and may be difficult to understand by laypeople. This could contribute to cause delays in appropriate OSA care and unrealistic treatment expectations, increasing the risk of treatment discontinuation.

The impact of GABAB receptors and their pharmacological stimulation on cocaine reinforcement and drug-seeking behaviors in a rat model of depression.

Depression and cocaine use disorder represent frequent co-current diagnoses and the GABAB receptors are involved in both conditions. This research involved the application of the animal model of depression (bulbectomy, OBX) and cocaine use disorder (self-administration) to assess the efficiency of GABAB receptor agonists, baclofen and SKF-97541, on cocaine rewarding property and reinforcement of seeking-behaviors in rats with depressive phenotype. Additionally, we applied immunoreactive techniques to determine changes in the expression of GABAB receptor subunit 1 and 2 in rats with depression and cocaine addiction. The results obtained the study illustrate that the GABAB receptor agonists reduced the rewarding property of cocaine in both OBX and control (SHAM) rats. Both agonists significantly reduced cue- and cocaine-induced reinstatement in both groups. This is the first report demonstrating a different impact of cocaine abuse on GABAB receptor levels in depressed animals. It was documented that the expression of GABAB1 subunit in the infralimbic cortex increased during self-administration and extinction training in OBX animals. The lower level of expression for this subunit in addictive SHAM rats during self-administration, and increased in extinguished addictive OBX rats was found in the ventrolateral striatum. The expression of GABAB2 subunit changed only in the case of cocaine self-administration paradigm, as a decline of the subunit level in the nucleus accumbens and ventral hippocampus was observed only in OBX rats. The relevance of GABAB receptors in depression and addiction comorbidity is clearly implicated and can open a new era of drug discovery for individuals with dual diagnosis.

DNA repair polymorphisms modify bladder cancer risk: a multi-factor analytic strategy.

OBJECTIVES: A number of common non-synonymous single nucleotide polymorphisms (SNPs) in DNA repair genes have been reported to modify bladder cancer risk. These include: APE1-Asn148Gln, XRCC1-Arg399Gln and XRCC1-Arg194Trp in the BER pathway, XPD-Gln751Lys in the NER pathway and XRCC3-Thr241Met in the DSB repair pathway. METHODS: To examine the independent and interacting effects of these SNPs in a large study group, we analyzed these genotypes in 1,029 cases and 1,281 controls enrolled in two case-control studies of incident bladder cancer, one conducted in New Hampshire, USA and the other in Turin, Italy. RESULTS: The odds ratio among current smokers with the variant XRCC3-241 (TT) genotype was 1.7 (95% CI 1.0-2.7) compared to wild-type. We evaluated gene-environment and gene-gene interactions using four analytic approaches: logistic regression, Multifactor Dimensionality Reduction (MDR), hierarchical interaction graphs, classification and regression trees (CART), and logic regression analyses. All five methods supported a gene-gene interaction between XRCC1-399/XRCC3-241 (p = 0.001) (adjusted OR for XRCC1-399 GG, XRCC3-241 TT vs. wild-type 2.0 (95% CI 1.4-3.0)). Three methods predicted an interaction between XRCC1-399/XPD-751 (p = 0.008) (adjusted OR for XRCC1-399 GA or AA, XRCC3-241 AA vs. wild-type 1.4 (95% CI 1.1-2.0)). CONCLUSIONS: These results support the hypothesis that common polymorphisms in DNA repair genes modify bladder cancer risk and highlight the value of using multiple complementary analytic approaches to identify multi-factor interactions.

Intake of fruits and vegetables and polymorphisms in DNA repair genes in bladder cancer.

The objective is to investigate the relationships between fruit and vegetable intake, DNA repair gene polymorphisms and the risk of bladder cancer. We have analyzed a hospital-based case-control study of 266 individuals with incident, histologically confirmed bladder cancer diagnosed between 1994 and 2003. Controls (n = 193) were patients treated for benign diseases recruited daily in a random fashion from the same hospital as the cases. All cases and controls were interviewed face-to-face for major risk factors, along fruit and vegetable consumption. Odds ratios (ORs) for fruit and vegetable intake and DNA repair gene polymorphisms were adjusted for age and smoking status, using unconditional logistic regression. A statistically significant decreased risk was observed for fruit and vegetable intake above median (versus below the median) [unadjusted OR 0.61, confidence interval (CI) 95% 0.50-0.96 and OR 0.54, CI 95% 0.39-0.80, respectively]; the decreased risk persisted after adjustment for age and cigarette smoking (OR 0.73, CI 95% 0.49-1.01 and OR 0.86, CI 95% 0.56-1.08, respectively). The fruits and vegetables associated with decreased risks included leafy green vegetables, cruciferous vegetables, apples and citrus fruits. We did not find any interactions between DNA repair gene polymorphisms and fruit and vegetable intake. This study found a reduced risk associated with fruit and vegetable intake. No interaction was observed between fruit and vegetable consumption and DNA repair gene polymorphisms.

Expression of DNA repair and metabolic genes in response to a flavonoid-rich diet.

A diet rich in fruit and vegetables can be effective in the reduction of oxidative stress, through the antioxidant effects of phytochemicals and other mechanisms. Protection against the carcinogenic effects of chemicals may also be exerted by an enhancement of detoxification and DNA damage repair mechanisms. To investigate a putative effect of flavonoids, a class of polyphenols, on the regulation of the gene expression of DNA repair and metabolic genes, a 1-month flavonoid-rich diet was administered to thirty healthy male smokers, nine of whom underwent gene expression analysis. We postulated that tobacco smoke is a powerful source of reactive oxygen species. The expression level of twelve genes (APEX, ERCC1, ERCC2, ERCC4, MGMT, OGG1, XPA, XPC, XRCC1, XRCC3, AHR, CYP1A1) was investigated. We found a significant increase (P < 0.001) in flavonoid intake. Urinary phenolic content and anti-mutagenicity did not significantly change after diet, nor was a correlation found between flavonoid intake and urinary phenolic levels or anti-mutagenicity. Phenolic levels showed a significant positive correlation with urinary anti-mutagenicity. AHR levels were significantly reduced after the diet (P = 0.038), whereas the other genes showed a generalized up regulation, significant for XRCC3 gene (P = 0.038). Also in the context of a generalized up regulation of DNA repair genes, we found a non-significant negative correlation between flavonoid intake and the expression of all the DNA repair genes. Larger studies are needed to clarify the possible effects of flavonoids in vivo; our preliminary results could help to better plan new studies on gene expression and diet.

Polymorphisms/haplotypes in DNA repair genes and smoking: a bladder cancer case-control study.

Bladder cancer is associated with tobacco smoking and occupational exposure. The repair of DNA damage has a key role in protecting the genome from the insults of cancer-causing agents. We analyzed 13 polymorphisms in seven DNA repair genes belonging to different repair pathways [X-ray repair cross-complementing group 1 (XRCC1): 26304C>T, 26651A>G, 28152A>G; xeroderma pigmentosum-D (XPD): 23591A>G, 35931A>C; excision repair complementing defective in Chinese hamster, group 1 (ERCC1): 19007C>T; XRCC3: 4541T>C, 17893A>G, 18067C>T; proliferating cell nuclear antigen (PCNA): 6084G>C; ERCC4: 30028C>T, 30147A>G; and XRCC2-31479A>G] in 317 incident bladder cancer patients and 317 controls. After adjustment for age and smoking, the PCNA-6084C variant was significantly associated with an increased risk of bladder cancer [CC + CG versus GG, odds ratio (OR), 1.61; 95% confidence interval (95% CI), 1.00-2.61], as well as the XRCC1-26651G variant (GG+AG versus AA: OR, 1.73; 95% CI, 1.17-2.56). After stratifying by smoking habits, an elevated risk for carriers of the XRCC3-18067T allele was detected both in current (TT versus CC: OR, 2.65; 95% CI, 1.21-5.80; CT versus CC: OR, 1.96; 95% CI, 1.09-3.52) and never smokers (TT versus CC: OR, 4.34; 95% CI, 1.14-16.46; CT versus CC: OR, 2.02; 95% CI, 0.72-5.66), whereas an opposite and slightly weaker effect was associated to the XRCC3-17893G allele in current smokers (GG versus AA: OR, 0.30; 95%CI, 0.11-0.82; AG versus AA: OR, 0.73; 95% CI, 0.42-1.27). XRCC3,XRCC1, ERCC4, and XPD-ERCC1 haplotype frequencies were estimated by the maximum likelihood method. The XRCC3-TAT haplotype was associated with an enhanced risk in the current smokers group (OR, 1.62; 95% CI, 1.15-2.29), whereas a reduction of the risk in the overall sample was observed in the presence of the XRCC3-TAC (OR, 0.69; 95% CI, 0.50-0.97). A significant protective effect of the XPD-ERCC1-ACC haplotype was observed among never smokers (OR, 0.16; 95% CI, 0.03-0.81). Our results suggest that polymorphisms and/or haplotypes in XRCC3, XRCC1, and PCNA genes and spanning XPD-ERCC1 region may modulate bladder cancer risk and that some of these effects may preferentially affect current smokers.

Interplay between scatter factor receptors and B plexins controls invasive growth.

Met and Ron tyrosine kinases are members of the Scatter Factor Receptor family. Met is the receptor for hepatocyte growth factor while Ron is that for macrophage stimulating protein. On ligand stimulation, activation of these receptors induces 'invasive growth', a complex biological response involved in tissue morphogenesis and, when deregulated, in tumor progression and metastasis. Scatter Factor Receptors share structural homology with Plexins, transmembrane receptors for Semaphorins, a family of ligands originally identified as axon guidance molecules. A physical and functional association between Met and Plexin B1, the prototype of class B Plexin subfamily, has been previously demonstrated. Here, we show that both Met and Ron receptors can interact with each of the three members of class B Plexins, even in the absence of their ligands and that Plexin B1 ligand, Sema 4D, can induce activation of Met and Ron receptors, promoting an invasive response. Furthermore, in some human neoplastic cell lines Plexin B1 is overexpressed, constitutively tyrosine phosphorylated, and associated with Scatter Factor Receptors. These data extend the crosstalk previously described between Met and Plexin B1 to the entire families of Scatter Factor Receptors and class B Plexins and show that interaction with multiple upstream activators can finely tune the invasive growth process both in physiological conditions and in tumor growth and metastatization.