Host-guest complexes of local anesthetics with cucurbit[6]uril and para-sulphonatocalix[8]arene in the solid state

© 2017 Elsevier B.V. Here we describe the host-guest inclusion complexes of local anesthetic drugs with two macrocyclic hosts cucurbit[6]uril and para-sulphonatocalix[8] arene in the solid state. The anesthetic agents used in the co-crystallization with the supramolecular hosts are lidocaine, procaine, procainamide, prilocaine and proparacaine. Both macrocycles encapsulate the alkylammonium moieties of anestetics guests into their cavities although the mechanism of complexation, host-guest stoichiometry and geometry differ depending on the nature of the supramolecular host

Acoustic localisation of wildlife with low-cost equipment: Lower sensitivity, but no loss of precision

Abstract Context Synchronised acoustic recorders can be used as a non-invasive tool to detect and localise sounds of interest, including vocal wildlife and anthropogenic sounds. Due to the high cost of commercial synchronised recorders, acoustic localisation has typically been restricted to small or well funded surveys. Recently, low-cost acoustic recorders have been developed, but until now their efficacy has not been compared with higher specification recorders. Aims The present study aimed to compare the efficacy of a newly developed low-cost recorder, the Conservation at Range through Audio Classification and Localisation (CARACAL), with an established, high-end recorder, the Wildlife Acoustics Song Meter (SM). Methods Four recorders of each type were deployed in a paired set-up across five nights in Wisconsin, USA. The recordings allowed for manual identification of domestic dog (Canis familiaris), grey wolf (Canis lupus), coyote (Canis latrans) and barred owl (Strix varia) calls, and then the ability of each recorder type to detect and localise the vocalising animals was compared. Key results The CARACALs were less sensitive, detecting only 47.5% of wolf, 55% of coyote, 65% of barred owl and 82.5% of dog vocalisations detected by the paired SMs. However, when the same vocalisations were detected on both recorders, localisation was comparable, with no significant difference in the precision or maximum detection ranges. Conclusions Low-cost recording equipment can be used effectively for acoustic localisation of both wild and domestic animals. However, the lower sensitivity of the CARACALs means that a denser network of these recorders would be needed to achieve the same efficacy as the SMs. Deploying a greater number of cheaper recorders increases the labour time in the field and the quantity of data to process and store. Thus, there is a trade-off between cost and time to be considered. Implications The ability to use low-cost recorders for acoustic localisation provides new avenues for tracking, managing and researching a wide range of wildlife species. Presently, CARACALs are more suited to monitoring species that have small home ranges and high amplitude vocalisations, and for when a large time investment for in situ equipment checks and data processing is feasible.Christine Stevens Wildlife Award from the Animal Welfare Institut

Differences in the haematological profile of healthy 70 year old men and women: normal ranges with confirmatory factor analysis

<p>Abstract</p> <p>Background</p> <p>Reference ranges are available for different blood cell counts. These ranges treat each cell type independently and do not consider possible correlations between cell types.</p> <p>Methods</p> <p>Participants were identified from the Community Health Index as survivors of the 1947 Scottish Mental Survey, all born in 1936, who were resident in Lothian (potential n = 3,810) and invited to participate in the study. Those who consented were invited to attend a Clinical Research Facility where, amongst other assessments, blood was taken for full blood count. First we described cell count data and bivariate correlations. Next we performed principal components analysis to identify common factors. Finally we performed confirmatory factor analysis to evaluate suitable models explaining relationships between cell counts in men and women.</p> <p>Results</p> <p>We examined blood cell counts in 1027 community-resident people with mean age 69.5 (range 67.6-71.3) years. We determined normal ranges for each cell type using Q-Q plots which showed that these ranges were significantly different between men and women for all cell types except basophils. We identified three principal components explaining around 60% of total variance of cell counts. Varimax rotation indicated that these could be considered as erythropoietic, leukopoietic and thrombopoietic factors. We showed that these factors were distinct for men and women by confirmatory factor analysis: in men neutrophil count was part of a 'thrombopoietic' trait whereas for women it was part of a 'leukopoietic' trait.</p> <p>Conclusions</p> <p>First, normal ranges for haematological indices should be sex-specific; at present this only pertains to those associated with erythrocytes. Second, differences between individuals across a range of blood cell counts can be explained to a considerable extent by three major components, but these components are not the same in men and women.</p

Polymorphisms in Nucleotide Excision Repair Genes, Arsenic Exposure, and Non-Melanoma Skin Cancer in New Hampshire

Background: Arsenic exposure may alter the efficiency of DNA repair. UV damage is specifically repaired by nucleotide excision repair (NER), and common genetic variants in NER may increase risk for non-melanoma skin cancer (NMSC). Objective: We tested whether polymorphisms in the NER genes XPA (A23G) and XPD (Asp312Asn and Lys751Gln) modify the association between arsenic and NMSC. Methods: Incident cases of basal and squamous cell carcinoma (BCC and SCC, respectively) were identified through a network of dermatologists and pathology laboratories across New Hampshire. Population-based controls were frequency matched to cases on age and sex. Arsenic exposure was assessed in toenail clippings. The analysis included 880 cases of BCC, 666 cases of SCC, and 780 controls. Results: There was an increased BCC risk associated with high arsenic exposure among those homozygous variant for XPA [odds ratio (OR) = 1.8; 95% confidence interval (CI), 0.9–3.7]. For XPD, having variation at both loci (312Asn and 751Gln) occurred less frequently among BCC and SCC cases compared with controls (OR = 0.8; 95% CI, 0.6–1.0) for both case groups. In the stratum of subjects who have variant for both XPD polymorphisms, there was a 2-fold increased risk of SCC associated with elevated arsenic (OR = 2.2; 95% CI, 1.0–5.0). The test for interaction between XPD and arsenic in SCC was of borderline significance (p < 0.07, 3 degrees of freedom). Conclusions: Our findings indicate a reduced NMSC risk in relation to XPD Asp312Asn and Lys751Gln variants. Further, these data support the hypothesis that NER polymorphisms may modify the association between NMSC and arsenic

Combined effects of cigarette smoking, gene polymorphisms and methylations of tumor suppressor genes on non small cell lung cancer: a hospital-based case-control study in China

<p>Abstract</p> <p>Background</p> <p>Cigarette smoking is the most established risk factor, and genetic variants and/or gene promoter methylations are also considered to play an essential role in development of lung cancer, but the pathogenesis of lung cancer is still unclear.</p> <p>Methods</p> <p>We collected the data of 150 cases and 150 age-matched and sex-matched controls on a Hospital-Based Case-Control Study in China. Face to face interviews were conducted using a standardized questionnaire. Gene polymorphism and methylation status were measured by RFLP-PCR and MSP, respectively. Logistic regressive model was used to estimate the odds ratios (OR) for different levels of exposure.</p> <p>Results</p> <p>After adjusted age and other potential confounding factors, smoking was still main risk factor and significantly increased 3.70-fold greater risk of NSCLC as compared with nonsmokers, and the ORs across increasing levels of pack years were 1, 3.54, 3.65 and 7.76, which the general dose-response trend was confirmed. Our striking findings were that the risk increased 5.16, 8.28 and 4.10-fold, respectively, for NSCLC with promoter hypermethylation of the <it>p16</it>, <it>DAPK </it>or <it>RARβ </it>gene in smokers with <it>CYP1A1 </it>variants, and the higher risk significantly increased in smokers with null <it>GSTM1 </it>and the OR was 17.84 for NSCLC with <it>p16 </it>promoter hypermethylation, 17.41 for <it>DAPK</it>, and 8.18 for <it>RARβ </it>in smokers with null <it>GSTM1 </it>compared with controls (all p < 0.01).</p> <p>Conclusion</p> <p>Our study suggests the strong combined effects of cigarette smoke, <it>CYP1A1 </it>and <it>GSTM1 </it>Polymorphisms, hypermethylations of <it>p16</it>, <it>DAPK </it>and <it>RARβ </it>promoters in NSCLC, implying complex pathogenesis of NSCLC should be given top priority in future research.</p

Effect of Polymorphisms in XPD on Clinical Outcomes of Platinum-Based Chemotherapy for Chinese Non-Small Cell Lung Cancer Patients

PURPOSE: Xeroderma pigmentosum group D (XPD) codes for a DNA helicase involved in nucleotide excision repair that removes platinum-induced DNA damage. Genetic polymorphisms of XPD may affect DNA repair capacity and lead to individual differences in the outcome of patients after chemotherapy. This study aims to identify whether XPD polymorphisms affect clinical efficacy among advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. EXPERIMENTAL DESIGN: 353 stage III-IV NSCLC patients receiving platinum-based chemotherapy as the first-line treatment were enrolled in this study. Four potentially functional XPD polymorphisms (Arg(156)Arg, Asp(312)Asn, Asp(711)Asp and Lys(751)Gln) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or PCR-based sequencing. RESULTS: Variant genotypes of XPD Asp(312)Asn, Asp(711)Asp and Lys(751)Gln were significantly associated with poorer NSCLC survival (P = 0.006, 0.006, 0.014, respectively, by log-rank test). The most common haplotype GCA (in order of Asp(312)Asn, Asp(711)Asp and Lys(751)Gln) also exhibited significant risk effect on NSCLC survival (log-rank P = 0.001). This effect was more predominant for patients with stage IIIB disease (P = 2.21×10(-4), log-rank test). Increased risks for variant haplotypes of XPD were also observed among patients with performance status of 0-1 and patients with adenocarcinoma. However, no significant associations were found between these polymorphisms, chemotherapy response and PFS. CONCLUSIONS: Our study provides evidence for the predictive role of XPD Asp(312)Asn, Asp(711)Asp and Lys(751)Gln polymorphisms/haplotype on NSCLC prognosis in inoperable advanced NSCLC patients treated with platinum-based chemotherapy