Risk for nicotine dependence and lung cancer is conferred by mRNA expression levels and amino acid change in CHRNA5.

Nicotine dependence risk and lung cancer risk are associated with variants in a region of chromosome 15 encompassing genes encoding the nicotinic receptor subunits CHRNA5, CHRNA3 and CHRNB4. To identify potential biological mechanisms that underlie this risk, we tested for cis-acting eQTLs for CHRNA5, CHRNA3 and CHRNB4 in human brain. Using gene expression and disease association studies, we provide evidence that both nicotine-dependence risk and lung cancer risk are influenced by functional variation in CHRNA5. We demonstrated that the risk allele of rs16969968 primarily occurs on the low mRNA expression allele of CHRNA5. The non-risk allele at rs16969968 occurs on both high and low expression alleles tagged by rs588765 within CHRNA5. When the non-risk allele occurs on the background of low mRNA expression of CHRNA5, the risk for nicotine dependence and lung cancer is significantly lower compared to those with the higher mRNA expression. Together, these variants identify three levels of risk associated with CHRNA5. We conclude that there are at least two distinct mechanisms conferring risk for nicotine dependence and lung cancer: altered receptor function caused by a D398N amino acid variant in CHRNA5 (rs16969968) and variability in CHRNA5 mRNA expression.

CVD grown GaSbxN1-x films as visible-light active photoanodes.

The III-V semiconductor GaN is a promising material for photoelectrochemical (PEC) cells, however the large bandgap of 3.45 eV is a considerable hindrance for the absorption of visible light. Therefore, the substitution of small amounts of N anions by isovalent Sb is a promising route to lower the bandgap and thus increase the PEC activity under visible light. Herein we report a new chemical vapor deposition (CVD) process utilizing the precursors bis(N,N'-diisopropyl-2-methyl-amidinato)-methyl gallium (III) and triphenyl antimony (TPSb) for the growth of GaSbxN1-x alloys. X-ray diffraction (XRD) and scanning electron microscopy (SEM) measurements show crystalline and homogeneous thin films at deposition temperatures in the range of 500-800 °C. Rutherford backscattering spectrometry (RBS) combined with nuclear reaction analysis (NRA) shows an incorporation of 0.2-0.7 at% antimony into the alloy, which results in a slight bandgap decrease (up to 0.2 eV) accompanied by enhanced sub-bandgap optical response. While the resulting photoanodes are active under visible light, the external quantum efficiencies remained low. Intriguingly, the best performing films exhibits the lowest charge carrier mobility according to time resolved THz spectroscopy (TRTS) and microwave conductivity (TRMC) measurements, which showed mobilities of up to 1.75 cm2 V-1 s-1 and 1.2 × 10-2 cm2 V-1 s-1, for each timescale, respectively.

Radical Surgery for Endometriosis: Analysis of Quality of Life and Surgical Procedure.

OBJECTIVE: The main aim of this study is to determine the improvement in quality of life in patients who have undergone radical surgery because of severe endometriosis. PATIENTS AND METHODS: This nonrandomized interventional study (quasi experimental) was carried out between January 2009 and September 2014. A total of 46 patients with diagnosis of severe endometriosis were included. Radical surgery, including hysterectomy, was performed. Acting as their own control group, the patients were asked to fill in a validated questionnaire of quality of life [Endometriosis Health Profile-5 (EHP-5)] and a visual analog scale of pain at the moment of the preoperative visit (one month prior to surgery) and six months after the surgery. RESULTS: Radical surgery for endometriosis was performed in 46 patients at our center over the period of six years. Among the patients, 73.9% of them had undergone previous surgery for endometriosis. In 82.6% of cases, a complete laparoscopic resection was carried out. Gastrointestinal tract resection was performed in 21.7%, and urinary tract resection was necessary in 8.7%. The mean age of the patients was 38.6 years. The rate of complications was 30.4%. Six months after the surgery, all items of the EHP-5 questionnaire had a lower score, which means an improvement in all aspects of quality of life related to endometriosis. The difference obtained between the scores before and after the surgery was statistically significant. The mean visual analog scale score before the surgery was 8.5, whereas it decreased to 1.4 after the surgery (P < 0.001). CONCLUSION: Performing a radical surgery is a difficult decision to make; however, it can provide optimal results in terms of improvement of quality of life and, therefore, should be considered when conservative therapy fails.

Cross-sectional study about primary health care professionals views on the inclusion of the vaccine against human papillomavirus in the vaccine schedules.

BACKGROUND: Although the inclusion of the HPV vaccine has been registered in Spain since 2007, vaccination rates are lower than expected. The patients wish to be vaccinated is heavily influenced by information they have received from many source. The Knowledge of primary health care professionals affects the information provided to patients and is fundamental in the decision making. The aim of this study is to assess the opinions of primary health care professionals on the vaccine against HPV and their knowledge about HPV infection and its links to with gynecological and oropharyngeal cancer. METHODS: Cross-sectional study. A 19-item survey was drawn up. It included questions on basic aspects of HPV infection and marketed vaccines, personal opinion about the inclusion in the immunization schedules and their level of prescription and recommendation to patients in their clinical practice. From October 2013 to December 2013, 607 surveys were distributed among 20 primary health centers affiliated to the University Hospital 12 de Octubre. The results were analyzed using SPSS statistical package. RESULTS: One hundred sixty four successfully completed surveys were obtained for analysis. 89 % of the professionals knew about the relationship between HPV infection and cervical cancer, 57.3 % did not know any of the serotypes against which vaccines are targeted; 40.4 % believed that there is insufficient data to support the commercialization of the vaccines. Of these, 65.7 % argue that there is no data of its long-term effectiveness, 13.4 % that there is no data as to its side effects, 13.4 % believed that the cost effectiveness is not worthwhile. CONCLUSIONS: There is a strong controversy among health professionals regarding the marketing and inclusion of HPV vaccine in immunization schedules. However, the knowledge of the primary care health professionals on key aspects of infection and vaccine protection are insufficient. The training of professionals in vaccination, cervical pathology and HPV infection should be improved to provide objective information on the use as this vaccine for patients.

Variants in nicotinic receptors and risk for nicotine dependence.

OBJECTIVE: A recent study provisionally identified numerous genetic variants as risk factors for the transition from smoking to the development of nicotine dependence, including an amino acid change in the alpha5 nicotinic cholinergic receptor (CHRNA5). The purpose of this study was to replicate these findings in an independent data set and more thoroughly investigate the role of genetic variation in the cluster of physically linked nicotinic receptors, CHRNA5-CHRNA3-CHRNB4, and the risk of smoking. METHOD: Individuals from 219 European American families (N=2,284) were genotyped across this gene cluster to test the genetic association with smoking. The frequency of the amino acid variant (rs16969968) was studied in 995 individuals from diverse ethnic populations. In vitro studies were performed to directly test whether the amino acid variant in the CHRNA5 influences receptor function. RESULTS: A genetic variant marking an amino acid change showed association with the smoking phenotype (p=0.007). This variant is within a highly conserved region across nonhuman species, but its frequency varied across human populations (0% in African populations to 37% in European populations). Furthermore, functional studies demonstrated that the risk allele decreased response to a nicotine agonist. A second independent finding was seen at rs578776 (p=0.003), and the functional significance of this association remains unknown. CONCLUSIONS: This study confirms that at least two independent variants in this nicotinic receptor gene cluster contribute to the development of habitual smoking in some populations, and it underscores the importance of multiple genetic variants contributing to the development of common diseases in various populations.