Nutrient dietary patterns and the risk of laryngeal cancer : an Italian case-control study

Introduction. Several studies have indicated a role of diet in the etiology of laryngeal cancer. Since foods and nutrients tend to be closely related and act synergistically, the pecific effect of each dietary component of interest may be difficult to identify and can be partly confounded by other dietary components. Dietary patterns have thus been proposed as a practical tool to describe the association between diet and cancer, given their ability to capture the variations in overall food intake (Newby, Tucker 2004). A few studies have investigated the role of diet on laryngeal cancer through factor analysis. Aims We applied exploratory principal component factor analysis (PCFA) to identify a posteriori dietary patterns for a multicentric case-control study conducted in Italy on cancer of the larynx. This a posteriori technique allows to integrate several dietary exposures (i.e. foods, food groups, nutrients) into a smaller number of dietary patterns, that are independent from one another and can be evaluated as risk factors in subsequent analysis for the assessment of cancer risk. Methods A case-control study of cancer of the larynx was conducted from 1992 and 2000 in the provinces of Milan and Pordenone, in the Northern Italy. Cases were 460 subjects (415 men, 45 women) admitted to major teaching and general hospitals in the study areas with incident, histologically confirmed squamous cell cancer of the larynx, diagnosed no longer than 1 year before the interview. Controls were 1088 subjects (863 men, 225 women) admitted to the same hospitals for a wide spectrum of acute, non-neoplastic conditions, unrelated to smoking or alcohol drinking, or long term modifications of diet. The subjects\u2019 diet was assessed using a valid and reproducible food frequency questionnaire (FFQ) including 78 foods and beverages, as well as a range of the most common Italian recipes. Subjects were asked to indicate the average weekly consumption for each dietary item; intakes lower than once a month were coded as 0.5 per week. To estimate the intake of various nutrients, an Italian food composition database was used. We performed an exploratory PCFA on a selected set of 28 major macro- and micro-nutrients. We preliminarily evaluated the correlation matrix to determine if it was factourable, trough visual inspection and statistical procedure (Bartlett\u2019s test of sphericity). Moreover, we evaluated the Kaiser-Meyer-Olkin measure and individual measures of sampling adequacy (Kaiser, 1974). We chose the number of factors to retain based on the following criteria: factor eigenvalue greater than 1, scree plot examination and factor interpretability. We applied a varimax rotation to the factor loadings matrix to achieve a simpler and more interpretable solution. We used nutrients with rotated factor loading greater or equal to 0.63 on a given factor to name the pattern. Factor scores were defined for each subject and for each factor following the weighted least square method. They indicate the degree to which each subject\u2019s diet conforms to one of the identified patterns. To examine the robustness of the identified dietary patterns, we performed a principal axis factor analysis on the standardized nutrients and a maximum likelihood factor analysis after logarithmic transformation of the original nutrients. We calculated factor scores referring to the multiple regression method and standardizing the results. The correlations between scores referring to the same factor calculated with different methods were equal to 1 for all the comparisons. We also performed factor analysis separately within male and female subsamples and within different centers. All these checks yielded dietary patterns consistent with PCFA the ones obtained on the overall sample. To assess the reliability and refine the identified factors, we evaluated the internal consistency of those nutrients with a loading greater than 0.40 using standardized Cronbach\u2019s coefficient alpha. We calculated coefficient alphas for each factor and coefficient alphas when item deleted (Cronbach, 1951). To confirm the internal reproducibility of the identified patterns, individuals were randomly placed into one of two equally sized groups, and PCFA was performed separately in both subsamples. For each factor, we grouped participants into three categories according to quintiles of factor scores among the control population, and estimated the odds ratio and corresponding 95% confidence intervals using unconditional multiple logistic regression models, including all the factors simultaneously. The model was adjusted for sex, age, study center, education, body mass index, physical activity, tobacco smoking, and alcohol drinking. Results Five factors were retained according to the defined criteria. These factors explained 79% of the total variance of the original nutrients. The first pattern, named Animal products, had the greatest loadings on calcium, phosphorus, riboflavin, animal protein, saturated fatty acids, zinc, and cholesterol. The second pattern, named Starch-rich, had the greatest loadings on starch, vegetable protein, and sodium. The third pattern, named Vitamins and fiber, had the greatest loadings on vitamin C, total fiber, beta-carotene equivalents, and total folate. The fourth pattern, named Seed oils, had the greatest loadings on linoleic acid, vitamin E, and linolenic acid. The fifth pattern, named Fish-rich, had the greatest loadings on other polyunsaturated fatty acids, and vitamin D. A direct association was observed between the Animal products pattern and laryngeal cancer (OR=1.94, 95% CI: 1.39-2.70). A borderline direct association was observed between the Starch-rich pattern and laryngeal cancer (OR=1.30, 95% CI: 0.93-1.81). An inverse relationship was observed between the Vitamins and fiber pattern and laryngeal cancer (OR=0.56, 95% CI: 0.41-0.76). No relationship was evident between the Seed oils pattern and laryngeal cancer (OR=0.98, 95% CI: 0.70-1.37). A direct association was found between the Fish-rich pattern and the laryngeal cancer (OR=2.09, 95% CI: 1.51-2.90). Conclusions The role of dietary habits on the risk of laryngeal cancer was evaluated through exploratory PCFA on 28 major nutrients of interest. We identified 5 major dietary patterns, explaining about 80% of the total variance of the original nutrients. Our results indicated that the Animal products and Fish-rich patterns are potentially unfavourable indicators of risk for laryngeal cancer, while the Vitamins and fiber pattern is inversely related to laryngeal cancer

Selected micronutrient intake and the risk of colorectal cancer.

The relationship between estimated intake of selected micronutrients and the risk of colorectal cancer was analysed using data from a case-control study conducted in northern Italy. The study was based on 828 patients with colon cancer, 498 with rectal cancer and 2,024 controls in hospital for acute, non-neoplastic, non-digestive tract diseases. Relative risks (RRs) of intake quintiles were computed after allowance for age, sex and other major potential confounding factors, including an estimate of total energy intake. No apparent trend in risk across intake quintiles was evident for retinol, vitamin D, methionine and calcium. For beta-carotene, ascorbic acid, vitamin E and folate there was a trend of a protective effect with increasing consumption: the RR for the highest versus the lowest quintile was 0.32 for beta-carotene, 0.40 for ascorbic acid, 0.60 for vitamin E and 0.52 for folate. These inverse associations were similar for colon and rectal cancer, and consistent across strata of sex and age. When simultaneous allowance was made for all these micronutrients, besides other covariates, the only persistent protective effects were for beta-carotene (RR = 0.38 for the highest quintile) and ascorbic acid (RR = 0.52). Whether this reflects a specific, or stronger, effect of these micronutrients, rather than problems of collinearity between micronutrients or other limitations of the data, remains open to discussion. Still, this study suggests that specific micronutrients may exert an independent protective effect against colorectal carcinogenesis

Dietary Patterns in Italy and the Risk of Renal Cell Carcinoma

Background: Conclusive evidence on foods, nutrients, or dietary patterns and the risk of renal cell carcinoma (RCC) is lacking in the literature. Methods: We considered data from an Italian hospital-based case\u2013control study (1992\u20132004) on 767 incident RCC cases and 1534 controls. A posteriori dietary patterns were identified by applying principal component factor analysis on 28 nutrients derived from a 78-item food-frequency questionnaire. We estimated the odds ratios (ORs) of RCC and corresponding 95% confidence intervals (CIs) for each quartile category (compared to the lowest one) using conditional multiple logistic regression models providing adjustment for major confounding factors. Results: We identified four dietary patterns, named \u201cAnimal products\u201d, \u201cStarch-rich\u201d, \u201cVitamins and fiber\u201d, and \u201cCooking oils and dressings\u201d. Higher intakes of the \u201cStarch-rich\u201d pattern were positively associated with RCC risk (OR = 1.38, 95% CI: 1.04\u20131.82 for the highest quartile, p = 0.018). The association was inverse with the \u201cCooking oils and dressings\u201d pattern (OR = 0.61, 95% CI: 0.47\u20130.80, p < 0.001), whereas no association was found with \u201cAnimal products\u201d and \u201cVitamins and fiber\u201d patterns. Conclusions: Higher intakes of starch-related foods may increase RCC risk, whereas consumption of olive and seed oils may favorably influence RCC risk

Development of Praziquantel sulphonamide derivatives as antischistosomal drugs

The almost empty armamentarium to treat schistosomiasis, a neglected parasitic disorder caused by trematode flatworms of the genus Schistosoma, except Praziquantel (PZQ), urged to find new alternatives to fight this infection. Carbonic Anhydrase from Schistosoma mansoni (SmCA) is a possible new target against this nematode. Here, we propose new PZQ derivatives bearing a primary sulphonamide group in order to obtain hybrid drugs. All compounds were evaluated for their inhibition profiles on both humans and Schistosoma CAs, X-ray crystal data of SmCA and hCA II in adduct with some inhibitors were obtained allowing the understanding of the main structural factors responsible of activity. The compounds showed in vitro inhibition of immature and adult S. mansoni, but further optimisation is required for improved activity

Crystal Structure of 4-Chlorocatechol 1,2-Dioxygenase from the Chlorophenol-utilizing Gram-positive Rhodococcus opacus 1CP

The crystal structure of the 4-chlorocatechol 1,2-dioxygenase from the Gram-positive bacterium Rhodococcus opacus (erythropolis) 1CP, a Fe(III) ion-containing enzyme involved in the aerobic biodegradation of chloroaromatic compounds, has been solved by multiple wavelength anomalous dispersion using the weak anomalous signal of the two catalytic irons (1 Fe/257 amino acids) and refined at a 2.5 A resolution (R(free) 28.7%; R factor 21.4%). The analysis of the structure and its comparison with the structure of catechol 1,2-dioxygenase from Acinetobacter calcoaceticus ADP1 (Ac 1,2-CTD) highlight significant differences between these enzymes. The general topology of the present enzyme comprises two catalytic domains (one for each subunit) related by a noncrystallographic 2-fold axis and separated by a common alpha-helical zipper motif consisting of five N-terminal helices from each subunit; furthermore the C-terminal tail is shortened significantly with respect to the known Ac 1,2-CTD. The presence of two phospholipids binding in a hydrophobic tunnel along the dimer axis is shown here to be a common feature for this class of enzyme. The active site cavity presents several dissimilarities with respect to the known catechol-cleaving enzyme. The catalytic nonheme iron(III) ion is bound to the side chains of Tyr-134, Tyr-169, His-194, and His-196, and a cocrystallized benzoate ion, bound to the metal center, reveals details on a novel mode of binding of bidentate inhibitors and a distinctive hydrogen bond network with the surrounding ligands. Among the amino acid residues expected to interact with substrates, several are different from the corresponding analogs of Ac 1,2-CTD: Asp-52, Ala-53, Gly-76, Phe-78, and Cys-224; in addition, regions of largely conserved amino acid residues in the catalytic cleft show different shapes resulting from several substantial backbone and side chain shifts. The present structure is the first of intradiol dioxygenases that specifically catalyze the cleavage of chlorocatechols, key intermediates in the aerobic catabolism of toxic chloroaromatics

Association between Nutrient-Based Dietary Patterns and Bladder Cancer in Italy

Limited knowledge is available on dietary patterns and bladder cancer risk. We analyzed data from an Italian case-control study carried out between 2003 and 2014, including 690 incident bladder cancer cases and 665 hospital-controls. We derived nutrient-based dietary patterns applying principal component factor analysis on 28 selected nutrients. We categorized factor scores according to quartiles, and estimated the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) through logistic regression models, adjusted for major confounding factors. We identified four dietary patterns named "Animal products", "Vitamins and fiber", "Starch-rich", and "Animal unsaturated fatty acids". We found an inverse association between the "Vitamins and fiber" pattern and bladder cancer (OR = 0.70, 95% CI: 0.48-0.99, IV versus I quartile category). Inverse relationships of borderline significance were also found for the "Animal products" and the "Animal unsaturated fatty acids" dietary patterns. No significant association was evident for the "Starch-rich" pattern. The current study allowed us to identify major dietary patterns in this Italian population. Our study confirms available evidence and shows that scoring high on a fruit-and-vegetables pattern provides beneficial effects on bladder cancer risk

Crystal structure of a blue laccase from Lentinus tigrinus: evidences for intermediates in the molecular oxygen reductive splitting by multicopper oxidases

<p>Abstract</p> <p>Background</p> <p>Laccases belong to multicopper oxidases, a widespread class of enzymes implicated in many oxidative functions in pathogenesis, immunogenesis and morphogenesis of organisms and in the metabolic turnover of complex organic substances. They catalyze the coupling between the four one-electron oxidations of a broad range of substrates with the four-electron reduction of dioxygen to water. These catalytic processes are made possible by the contemporaneous presence of at least four copper ion sites, classified according to their spectroscopic properties: one type 1 (T1) site where the electrons from the reducing substrates are accepted, one type 2 (T2), and a coupled binuclear type 3 pair (T3) which are assembled in a T2/T3 trinuclear cluster where the electrons are transferred to perform the O₂reduction to H₂O.</p> <p>Results</p> <p>The structure of a laccase from the white-rot fungus <it>Lentinus (Panus) tigrinus</it>, a glycoenzyme involved in lignin biodegradation, was solved at 1.5 Å. It reveals a asymmetric unit containing two laccase molecules (A and B). The progressive reduction of the copper ions centers obtained by the long-term exposure of the crystals to the high-intensity X-ray synchrotron beam radiation under aerobic conditions and high pH allowed us to detect two sequential intermediates in the molecular oxygen reduction pathway: the "peroxide" and the "native" intermediates, previously hypothesized through spectroscopic, kinetic and molecular mechanics studies. Specifically the electron-density maps revealed the presence of an end-on bridging, μ-η₁:η₁peroxide ion between the two T3 coppers in molecule B, result of a two-electrons reduction, whereas in molecule A an oxo ion bridging the three coppers of the T2/T3 cluster (μ3-oxo bridge) together with an hydroxide ion externally bridging the two T3 copper ions, products of the four-electrons reduction of molecular oxygen, were best modelled.</p> <p>Conclusion</p> <p>This is the first structure of a multicopper oxidase which allowed the detection of two intermediates in the molecular oxygen reduction and splitting. The observed features allow to positively substantiate an accurate mechanism of dioxygen reduction catalyzed by multicopper oxidases providing general insights into the reductive cleavage of the O-O bonds, a leading problem in many areas of biology.</p

Analyzing electronic momentary assessment data on chronic pain and weather conditions : a first look

Although scientific evidence is scarce, patients affected by chronic masticatory muscle pain often report increased pain in response to changes in weather conditions. The aim of the present study was to assess a potential relationship between pain intensity and meteorological factors, through a newly developed, portable device, in this population. Seven female subjects diagnosed with myofascial pain of the masticatory muscles participated in the study. Each patient was provided with a portable data logger that recorded and stored weather variables every 15 minutes. Patients were asked to record the level of perceived pain on an electronic visual analogue scale (VAS) every hour. The relationship between meteorological variables and pain scores was investigated using separate generalized least squares regression models with a correlation structure estimated via autoregressive integrated moving average models