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Background and aims: Increasing literature data show that adherence to the Mediterranean diet is undergoing profound changes in recent years, albeit with marked differences across nations. In Italy, one of the cradles of the Mediterranean diet, the literature regarding the trend for Mediterranean diet adherence is conflicting. Thus, we aimed to explore the trends of adherence to the Mediterranean diet in a large cohort of participants living in South Italy, over 20 years from 1985–86 to 2005–06. Methods and results: Cross-sectional study with two evaluations, one made in 1985–86 and another in 2005–06; all participants were adults aged 30–70 years of age. The adherence to the Mediterranean diet was evaluated using the score proposed by Panagiotakos et al. This score features values ranging from 0 to 55, higher scores reflecting a greater adherence. The data are reported by age (30–49 vs. 50–69 years). Overall, 2451 subjects were included in 1985–86 and 2375 in 2005–06. A significant reduction was observed in the adherence to the Mediterranean diet (age 30–49 years: 31.82 ± 4.18 in 1985–86 vs. 29.20 ± 4.48 in 2005–06, reduction by 8.2%, p < 0.0001; age 50–69: 32.20 ± 4.09 in 1985–86 vs.30.15 ± 4.27 in 2005–06, reduction by 6.3%, p < 0.0001). Among all these items, the most dramatic change was observed for olive oil consumption, that decreased by 2.35 points in younger and 0.89 in older people. Conclusion: The adherence to the Mediterranean diet decreased from 1985–86 to 2005–06 in South Italy, particularly in younger people, above all due to a decreased olive oil consumption. © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University

Background: Higher Dietary Inflammatory Index (DII®) scores are associated with increased morbidity and mortality. However, little is known about the effects of DII on mortality in Mediterranean countries. Therefore, in the present study, we aimed to investigate the potential association between DII scores and overall, cancer and cardiovascular disease (CVD) mortality in people living in a Mediterranean area. Methods: DII scores were calculated using a validated food-frequency questionnaire. DII scores were then categorised into tertiles. Mortality was ascertained via death certificates. The association between DII scores with overall and cause-specific mortality was assessed via a multivariable Cox's regression analysis and reported as hazard ratios (HRs) with their 95% confidence intervals (CIs). Results: The study included 1565 participants (mean age65.5years; females44.7%). After a median follow-up of 12years (2005–2017), 366 (23.4%) participants died. After adjusting for 17 potential confounders, people with higher DII scores had an increased risk of death compared to those in the lowest (most anti-inflammatory) tertile (HR=1.38; 95% CI=1.04–1.82 for the second tertile; HR=1.38; 95% CI=1.03–1.86 for the third tertile). Each 1 SD increase in DII score increased the risk of death by 13%. No association was found between DII scores and cancer or CVD death when considered separately. Conclusions: Higher DII scores were associated with a significantly higher mortality risk, whereas the association with cause-specific mortality was less clear. These findings highlight the potential importance of diet in modulating inflammation and preventing death. © 2019 The British Dietetic Association Ltd.

The study was aimed to investigate the role of radiotherapy (RT) as a risk factor for reactivation or worsening of symptoms in patients affected by rheumatoid arthritis (RA) PATIENTS AND METHODS: This is a single-center retrospective observational study on RA patients who developed cancer requiring RT during the course of the disease. The control group consisted of RA patients with cancer who did not undergo RT. In both groups, the disease activity was evaluated at baseline and at 6 and 12 months through the DAS28 index. A relapse was defined as an increase of20% in DAS28. A radiotherapist evaluated total and daily doses and timing of radiation. Acute and late toxicity was defined as events occurring within 90 days from the start and more than 90 days after the completion of RT, respectively.Seventy-two RA patients (38F/34M; mean age: 70±9 years; mean disease duration: 13±9 years), 29 (40.2%) of whom received radiotherapy (mean age 72.9±9 years), were enrolled. The most frequent malignancies were breast (27.2%), thyroid (9.8%), and skin (7%). Between radio-treated and non-radio-treated patients, no significant differences in RA reactivation (6/29 vs. 17/43; p=0.12) or mean exacerbation time (6.7 ± 4.9 months compared to 6.4 ± 4.1 months; p=0.78) were found. Overall, RT was well tolerated with low rates of both acute and late toxicity.In RA patients, RT was well tolerated and not associated with an increased risk of articular flares. Properly designed prospective clinical studies with a larger number of patients should be performed to confirm these data.

Background/Aim: Low-density lipoproteins (LDL) are a heterogeneous class of particles that differ in size and density from each other. Small dense LDL (sdLDL) particles are considered more atherogenic than larger particles. The aim of the study was to evaluate serum levels of sdLDL in patients who died from cardiovascular diseases (CVD) or cancer in a cohort of patients followed up in the De Bellis Research Hospital for 20 years. Patients and Methods: A total of 75 participants who died of cancer and 87 who died of CVD were enrolled and they were matched for age and sex with 135 healthy controls, i.e. without CVD or cancer and are still alive. Results: Patients who died from cancer had the highest value of LDL IV subfraction (0.25±1.16), followed by those who died from CVD (0.17±0.96). Conclusion: The integrated profile of sdLDL between CVD and cancer suggests that therapeutic modulation of sdLDL may be associated with a risk reduction for these diseases. © 2019 International Institute of Anticancer Research. All rights reserved.

Coffee drinking seems to have several beneficial effects on health outcomes. However, the effect on hepatic steatosis, depending on a high alcohol consumption (AFLD, alcoholic fatty liver disease) or on metabolic factors (non-alcoholic fatty liver disease, NAFLD), is still equivocal. Thus, we aimed to explore the potential association between coffee consumption and the presence and severity of hepatic steatosis in people with NAFLD or AFLD. In this cross-sectional study, coffee drinking was recorded using a semi-quantitative food frequency questionnaire, and categorized as yes vs. no and as 0, 1, 2, ≥3. The degree of fatty liver was assessed through a standardized ultrasound examination (score 0 to 6, with higher values reflecting higher severity). Liver steatosis was classified as NAFLD or AFLD on daily alcohol intake >30 g/day for men and >20 g/day for women. This study included 2819 middle-aged participants, the great majority were coffee drinkers (86.1%). After adjusting for 12 potential confounders, drinking coffee was not associated with decreased odds for NAFLD (n = 916) (odds ratio, OR = 0.93, 95% confidence intervals, CI: 0.72-1.20) or AFLD (n = 276) (OR = 1.20, 95% CI: 0.66-2.0). The consumption of coffee (categorized as yes vs. no), or an increased consumption of coffee were not associated with the presence of mild, moderate or severe liver steatosis in either NAFLD or AFLD. In conclusion, coffee intake was not associated with any lower odds of hepatic steatosis in either non-alcoholic or alcoholic forms in this large cohort of South Italian individuals. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Background Hepatocellular carcinoma (HCC) is a heterogeneous disease with both tumor and liver factors being involved. Aims To investigate HCC clinical phenotypes and factors related to HCC size. Methods Prospectively-collected HCC patients' data from a large Italian database were arranged according to the maximum tumor diameter (MTD) and divided into tumor size terciles, which were then compared in terms of several common clinical parameters and patients' survival. Results An higer MTD tercile was significantly associated with increased blood alpha-fetoprotein (AFP), gamma-glutamyl transpeptidase (GGTP), and platelet levels. Patients with higher platelet levels had larger tumors and higher GGTP levels, with lower bilirubin levels. However, patients with the highest AFP levels had larger tumors and higher bilirubin levels, reflecting an aggressive biology. AFP correlation analysis revealed the existence of 2 different groups of patients: those with higher and with lower AFP levels, each with different patient and tumor characteristics. The Cox proportional-hazard model showed that a higher risk of death was correlated with GGTP and bilirubin levels, tumor size and number, and portal vein thrombosis (PVT), but not with AFP or platelet levels. Conclusions An increased tumor size was associated with increased blood platelet counts, AFP and GGTP levels. Platelet and AFP levels were important indicators of tumor size, but not of survival.

To establish the differential diagnosis from choroidal melanoma and other malignant tumors.We report 5 patients with vasoproliferative tumors studied in our Hospital since 1993; diagnosis was mainly based on clinic appearance of the lesions. Each patient had undergone indirect ophthalmoscopy and ocular echography.Three upon five cases (studied before 1995) were treated with brachytherapy with Ir(192) because they were suspected to be choroidal melanomas. Periodical observation and treatment of associated complications was the treatment of choice in two other cases in which these complications determined the final visual acuity.It is important to establish the differential diagnosis between choroidal melanoma and other malignant tumors, as their prognosis and treatment are different.

Background: Hepatocellular carcinoma prognosis depends on both liver and tumor determinants, especially on maximum tumor diameter, multifocality, and presence of portal vein thrombosis, despite apparently complete tumor removal by resection or liver transplantation. Aims: To examine parameters of hepatocellular carcinoma aggressiveness as tumor size increases. Methods: A large hepatocellular carcinoma database was examined for trends in serum alpha-fetoprotein and the percentage of patients with macroscopic portal vein thrombosis or tumor multifocality. Results: A total of 13,016 hepatocellular carcinoma patients were identified having full tumor and survival data. Of these, 76.56% were male and 23.44% were female, with a median age of 64.4 years. We found that as the maximum tumor diameter increased, there was a significant trend for increased alpha-fetoprotein levels ( PConclusions: The greater fold-increases in alpha-fetoprotein and portal vein thrombosis compared with increases in maximum tumor diameter imply that hepatocellular carcinoma characteristics may change with increasing size to a more aggressive phenotype, suggesting that follow-up tumor sampling might be useful, in addition to baseline tumor sampling, for optimal therapeutic choices to be made.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons., Dutch Research Council (NWO); VENI Scheme Grant; VIDI Grant; Prinses Beatrix Spierfonds; Neuromuscular Fellowship Grant; Medical Research Council (MRC); Clinical Infrastructure Award; Epidemiology Unit; Integrative Epidemiology Unit; Canadian Institutes of Health Research; IWT; National Institute on Aging; National Health and Medical Research Council (NHMRC); Enabling Grant; NHMRC/Australian Research Council Strategic Award; NHMRC; NHMRC Centre of Research Excellence Grant; National Health and Medical Research Council of Australia (NHMRC) Research Fellowship; United Kingdom, Medical Research Council; Economic and Social Research Council; European Union (EU); Horizon 2020; European Community's Health Seventh Framework Programme; EuroMOTOR; European Research Council (ERC); Research and Innovation Programme; EScORIAL; ALS Foundation Netherlands; Alzheimer’s Society PhD Studentship; ARSla Funding; Biogen; University of Bristol; Motor Neurone Disease Association (MNDA); NIHR Maudsley Biomedical Research Centre; Dutch Ministry of Education, Culture, and Science; Netherlands Organization for Scientific Research (NWO; BRAINSCAPES); Gravitation Program; ALS Liga België; National Lottery of Belgium; KU Leuven Opening the Future Fund; KU Leuven Funds, “Een Hart voor ALS”, “Laeversfonds voor ALS Onderzoek” and the “Valéry Perrier Race against ALS Fund”; E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders; ALS Liga België; “Live now” Charity Foundation; Moscow ALS palliative Care Service; Canadian Institutes of Health; Research Australia; Ice Bucket Challenge Grant; NIH Intramural Research Programs; FightMND Mid-Career Fellowship; NIHR Senior Investigator; Sheffield NIHR Biomedical Research Centre; Motor Neurone Disease Association; National Institute for Health Research (NIHR) Biomedical Research Centre; Maudsley NHS Foundation Trust; King’s College London; NIHR Senior Investigator Award; Netherlands Organization for Health Research and Development; Vici Scheme; Netherlands Organization for Health Research and Development STRENGTH Project; PPP Allowance

Objective: The consumption of potatoes is increasing worldwide, but few studies have assessed the association between potato consumption and mortality, particularly in Mediterranean countries. We therefore investigated whether potato consumption is associated with higher risk of death in a large cohort of people living in South Italy. Design: Longitudinal. Setting: Community-dwelling. Measurements: 2,442 participants coming from MICOL and NUTRIHEP studies aged more than 50 years at baseline were followed-up for 11 years. Dietary intake was assessed by means of a Food Frequency Questionnaire. Potato consumption was categorized in quintiles according to their daily consumption (< 3.95, 3.96-8.55, 8.56-15.67, 15.68-22.0, and > 22.0 g/day). Mortality was ascertained through validated cases of death. The association between potato consumption and mortality was assessed through Cox’s regression models, adjusted for potential confounders, and reporting the data as hazard ratios (HRs) with 95% confidence intervals (CIs). Results: The 2,442 eligible participants were prevalently males (54.6%) and aged a mean of 64.3±9.3 years. During the 11-year follow-up, 396 (=16.2%) participants died. After adjusting for 12 potential baseline confounders, and taking those with the lowest consumption of potatoes as the reference group, participants with the highest consumption of potatoes did not have an increased overall mortality risk (HR=0.75; 95%CI: 0.53-1.07). Modelling the potato consumption as continuous (i.e. as increase in 10 g/day) did not substantially change our findings (fully-adjusted HR=0.93; 95%CI: 0.84-1.02). Conclusion: Overall potato consumption was not associated with higher risk of death in older people living in a Mediterranean area. Future studies are warranted to elucidate the role of potato consumption on all-cause and cause-specific mortality. © 2018, Serdi and Springer-Verlag France SAS, part of Springer Nature.

Objective:In the postmenopausal period, most women suffer vasomotor symptoms (VMS). It is well-known that VMS can worsen the quality of life. Diet seems to play a relevant role in the development of VMS, but the effect of diet on VMS is mainly limited to observational studies, and analyses of nutritional supplements. The aim of this study was thus to determine the efficacy of a lactoovo- vegetarian (LOVe) diet rich in omega-3 fatty acids vs. a lacto-ovo-vegetarian diet rich in EVO (extra-virgin olive oil) in reducing VMS frequency in postmenopausal women.Methods:A two-arms (lacto-ovo-vegetarian diet with EVO vs. lacto-ovo-vegetarian diet rich in omega-3) randomized-controlled trial with a follow-up period of 16 weeks. We considered as primary outcome the change in the Kupperman index (follow-up vs. baseline evaluation, reported as delta, D) and in its subscales. Secondary outcomes included changes in common anthropometric and biohumoral measurements.Results:Among 54 women randomly assigned to a study group, 40 (mean age 55.1±5.4 years) completed the study and complied with their assigned diet. Women randomized to the omega-3 group (n=18) showed significant improvements, compared to the EVO group (n=22), in Kupperman index (Δ=-11.4±9.8 vs. -5.9±8.2; p=0.045), hot flashes (Δ=-3.3±3.4 vs. -1.3±2.6; p=0.04), and a marginally significant improvement in nervousness (Δ=-1.7±1.7 vs. -0.8±1.5; p=0.07). No significant differences were observed for the secondary outcomes. No relevant side effects were reported.Conclusion:After 16 weeks, a lacto-ovo-vegetarian diet rich in omega-3 reduced VMS frequency in postmenopausal women more than the lacto-ovo-vegetarian diet rich in EVO.

Background: Irritable bowel syndrome (IBS)is the most frequent functional gastrointestinal disorder, both in primary and secondary care. Aims: (1)To describe diagnostic tools and treatments suggested to IBS patients by Italian gastroenterologists; (2)To evaluate patients’ quality of life and psychological involvement and the relationship of these factors with symptom severity. Methods: Twenty-six gastroenterologists recorded the demographic and clinical data of 677 IBS patients. Diagnostic and treatment measures taken in the previous year and those suggested by gastroenterologists were analysed. Results: IBS with constipation was found in 43.4%, with diarrhoea in 21.6%, mixed-IBS in 35.0%. Routine blood tests, ultrasonography, colonoscopy, barium enema and CT were more frequently requested in the previous year than by the gastroenterologists (p < 0.001). Colonoscopy (11%), and ultrasonography (20.4%)were also suggested by the gastroenterologists in a non-negligible number of patients. Abdominal pain and distension, bowel dissatisfaction, anxiety and depression were more severe in females than in males. Quality of life decreased with increasing IBS-symptom severity. Conclusions: IBS diagnosis is still largely based on exclusion criteria even if gastroenterologists try to improve diagnostic appropriateness. However, therapy remains symptom-based also in the gastroenterological setting even if gastroenterologists use a wide variety of approaches, including innovative therapies such as linaclotide and psychotherapy.

Non-alcoholic fatty liver disease (NAFLD) is a common condition in Western countries. However, their metabolic characteristics are poorly known even though they could be important. Therefore, the objective of this study was to measure resting metabolic parameters in overweight/obese adults with hepatic steatosis compared to controls, matched for age, sex, and obesity level. Hepatic steatosis was diagnosed with liver ultrasound. Energy metabolism was measured with indirect calorimetry: energy expenditure (REE), predicted REE, the ratio between REE and the predicted REE, and the respiratory quotient (RQ) were reported. We measured some anthropometric, body composition, and bio-humoral parameters, 301 participants with NAFLD were matched for age, sex, and obesity level with 301 participants without NAFLD. People with NAFLD showed significantly higher REE (1523 &plusmn, 238 vs. 1464 &plusmn, 212 kcal, p = 0.005), REE/REE predicted ratio (98.2 &plusmn, 9.4 vs. 95.7 &plusmn, 8.1, p = 0.002), and RQ (0.88 &plusmn, 0.08 vs. 0.85 &plusmn, 0.07, p = 0.03). Moreover, the NAFLD group had significantly higher inflammatory and insulin-resistance parameters compared to controls. In conclusion, NAFLD is associated with a significantly higher metabolic expenditure, as measured with indirect calorimetry, compared to a similar cohort of individuals without this condition. Higher inflammatory levels in patients with NAFLD can probably explain our findings, even if other research is needed on this issue.

There is still room for further studies analyzing the long-term health impact of specific dietary patterns observable in regions belonging to the Mediterranean area. The aim of the study is to evaluate how much a diet practiced in southern Italy is associated to a risk of mortality. The study population included 2472 participants first investigated in 1985, inquiring about their frequencies of intake of 29 foods using a self-administered questionnaire covering the previous year. The population was followed up for mortality until 31 December 2017. Cox-based risk modeling referred to single foods, food groups, the results of principal component analysis (PCA), and a priori indexes. Single food analysis revealed eggs, fatty meat, and fatty/baked ham to be inversely associated with mortality. Furthermore, one of the 5 PCA derived dietary patterns, the &ldquo, Farmhouse&rdquo, pattern, showed a higher hazard ratio (HR), mostly driven by dairy products. In subsequent analyses, the increased risk of mortality for fresh cheese and decreased risk for fatty ham and eggs were confirmed. The a priori diet indexes (Italian Meddiet, Meddietscore, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean&ndash, DASH Intervention for Neurodegenerative Delay diet (MIND) indexes) showed borderline inverse relationships. In a Mediterranean population with an overall healthy diet, foods such as eggs and fatty meat, reflecting dietary energy and wealth, played a role in prolonging the life of individuals. Our study confirms that some dairy products might have a detrimental role in mortality in the Mediterranean setting.

The early detection of colorectal cancer and determination of its metastatic potential are important factors to set up more efficacious therapeutic strategies. In the present study, we hypothesize that fatty acids analysis in colorectal cancer patients can discriminate between metastatic and non-metastatic patients. Fifty-one consecutive patients with histologically proven colorectal cancer were enrolled in the study and the presence of synchronous metastasis was detected in 25 of these 51 patients. Fatty acid profile analysis in red blood cell membranes was not able to discriminate the metastatic colorectal cancer patients from those without metastasis. However, significant differences in the tumor tissue fatty acid profile were found in metastatic cancer patients when compared to patients without metastasis. Metastatic patients showed significantly lower percentages of Eicosapentaenoic acid (EPA) and higher levels of γ-linolenic acid (GLA), a n-3- and n-6-Polyunsaturated fatty acid (PUFA), respectively. Our findings, suggesting that membrane lipid rearrangement could influence the cellular function and make the cell more prone to metastasis, offer the opportunity to develop nutritional strategies that may be helpful in the prevention and treatment of colorectal cancer. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

ObjectiveAlcoholic fatty liver (AFLD) and non-alcoholic fatty liver (NAFLD) are two common conditions. However, if they can increase the risk of death is poorly explored. We therefore aimed to investigate the potential association between the presence and severity of liver steatosis and mortality in a large sample of older people.DesignProspective.SettingCommunity.ParticipantsWomen and men randomly sampled from the electoral rolls of the population of Castellana Grotte, a town in Southern Italy (Apulia region) between 2005 and 2006. Among 1942 initially contacted, 1708 (=87.9%) participated to the baseline survey (Multicentrica Colelitiasi III (MICOL III)). This specific study included 1445 older participants (mean age=65.2 years, females=44.2%).ExposureNAFLD or AFLD.Primary and secondary outcomesMortality (all-cause and specific-cause).ResultsAfter a median of 12 years, 312 participants (=21.6%) died. After adjusting for nine potential confounders, the presence of steatosis was not associated with any increased risk of death in both NAFLD and AFLD. The severity of liver steatosis was not associated with any increased risk of mortality in NAFLD, while in AFLD, the presence of moderate steatosis significantly increased the risk of overall (HR=2.16; 95% CI 1.19 to 3.91) and cancer-specific (HR=3.54; 95% CI 1.16 to 10.87) death.ConclusionsLiver steatosis is not associated with any increased risk of death in NAFLD, while moderate steatosis could be a risk factor for mortality (particularly due to cancer) in people affected by AFLD.

Background: Clinical phenotypes of small and large hepatocellular carcinomas (HCCs) are not well characterized. Aim: To evaluate the characteristics of small HCCs diagnosed by screening. Method: A cohort of 430 small HCCs that were diagnosed through screening, were dichotomized according to a size of ≤3 cm or >3 cm maximum tumor diameter and compared for radiological and blood-test parameters. Results: There were 330 males and 100 females. A higher percent of females had smaller tumors. The majority of patients had single tumors, but 15% of those with larger tumors had portal vein thrombosis (PVT) compared to 5% of those with smaller tumors. Significant differences between the tumor-size groups included alpha-fetoprotein (AFP) values and platelet counts, with thrombocytopenia and elevated bilirubin levels being associated with smaller tumors. In comparing PVT-positive and PVT-negative patients, AFP levels and platelet counts were also significantly different between the 2 groups. A mean multinomial multiple logistic regression model was developed for maximum tumor diameter plus PVT. Conclusions: The finding of larger tumors being associated with normal platelets and bilirubin levels in comparison to smaller tumors having thrombocytopenia reveals 2 different patterns of HCC presentation.

OBJECTIVE: The aim of our study was to analyse the frequency of beta1 and/or beta2 adrenergic receptor polymorphisms in patients with takotsubo cardiomyopathy (TTC). METHODS AND RESULTS: beta1 and/or beta2 adrenergic receptor polymorphisms in 61 patients with TTC were compared with 109 controls. The beta1 adrenoreceptor (amino acid position 389) genotype frequencies were significantly different in the two groups; assuming a recessive model for the allelic variant coding for Arg on this position, the odds ratio was 3.14, 95% Cl 1.55-6.37 (P = 0.0015). The beta2 adrenoreceptor amino acid position 27 genotype was significantly different and assuming a recessive model for the allelic variant coding for Gln on this position, the odds ratio was 0.29, 95% Cl 0.12-0.74 (P = 0.009). CONCLUSIONS: This study showed for the first time an association between TTC phenotype and beta1 adrenoreceptor gene polymorphisms. Beta adrenoreceptors gene polymorphisms are probably disease modifiers, and any risk estimate should be based on a combination of genotypes and on interactions with other genes and environmental features.

Background: Cannabinoid type 1 receptor (CB1-R) is a key mediator in the control of food intake and is linked to obesity. Aim: To evaluate the relationship between CB1-R gene polymorphism and dietary macronutrient intake in elderly subjects. Methods: This study included 118 subjects (60 males, 58 females) from a population survey carried out in southern Italy in 1992–1993 who were older than 65 years and previously characterized for CB1-R polymorphism (75 with GG wild-type genotype, 41 with heterozygous polymorphic allele AG, and 2 with genotype AA). All subjects completed a validated semi-quantitative food frequency questionnaire. Statistical methods included multiple logistic regression to model macronutrient intake to genotype, controlling for potential confounders. Results: When controlled for age, gender, and body mass index, the intake of dietary cholesterol and saturated fats corrected for calories was inversely associated with the CB1-R 1359 G/A polymorphism, while the intake of starchy carbohydrates was directly associated with this polymorphism. Conclusion: In our unselected elderly population, the 1359 G/A polymorphism is linked with a specific macronutrient intake. This could be explained by the role of the cannabinoid system as a determinant of food intake and eating behavior.

Little is known about the pathophysiology of diverticular disease.To compare passive and active stress and the response to carbachol of colonic smooth muscle specimens from patients with diverticular disease and patients with colon cancer. The effect of the NK2 receptor antagonist, SR48968, on electrically evoked contractions of circular muscle was also investigated.Sigmoid colon segments were obtained from 16 patients (51-83 years) undergoing elective sigmoid resection for diverticular disease and 39 patients (50-88 years) undergoing left hemicolectomy for non-obstructive sigmoid colon cancer.Isometric tension was measured on circular or longitudinal taenial muscle. Strips were stretched gradually to Lo (length allowing the development of optimal active tension with carbachol) and were also exposed to increasing carbachol concentrations. The effects of atropine, tetrodotoxin and SR48968 on electrically evoked (supramaximal strength, 0.3 ms, 0.1-10 Hz) contractions of circular strips from 8 patients with diverticular disease and 19 patients with colon cancer were also studied.Both passive and active stress in circular muscle strips obtained from patients with diverticular disease was higher than in patients with colon cancer (P0.05). Electrically evoked contractions were significantly reduced by atropine in all preparations and were virtually suppressed by combined SR48968 and atropine. Tetrodotoxin suppressed electrically evoked contractions only in patients with colon cancer, whereas a tetrodotoxin-resistant component was identified in patients with diverticular disease.The changes in both passive and active stress in specimens from patients with diverticular disease may reflect circular smooth muscle dysfunction. Acetylcholine and tachykinins are the main excitatory neurotransmitters mediating electrically evoked contractions in human sigmoid colon circular muscle.

Background The enzyme farnesyltransferase has emerged as an important target for anti-cancer therapies. Farnesyltransferase inhibitors have been introduced in clinical trials of subjects with colorectal cancer. We investigated Farnesyltransferase activity, beta-subunit Farnesyltransferase protein expression and its mRNA in patients with colorectal cancer and its relationship with clinicopathological features and K-ras mutation. Methods Farnesyltransferase activity was determined by Farnesyltransferase [3H] SPA enzyme assay. Beta-subunit Farnesyltransferase protein expression was investigated by Western blotting and its mRNA by reverse transcriptase-polymerase chain reaction. K-ras mutation was detected by polymerase chain reaction amplification and restriction enzyme analysis. Multiple linear regression analysis was used to analyse relationships among age, sex, site of tumour, Dukes' stage, histological differentiation, K-ras mutation and Farnesyltransferase activity in normal mucosa and cancer. Results The levels of Farnesyltransferase activity and beta-subunit Farnesyltransferase protein expression were significantly higher in cancer than in normal mucosa. Moreover, tumours located on the right side, with mucinous histological differentiation and with K-ras mutation showed higher levels of Farnesyltransferase activity. Conclusions Our findings suggest that Farnesyltransferase activity may be a potential marker of tumourigenicity. The differences in Farnesyltransferase activity in relation to histological grading, tumour location and K-ras mutation described here may constitute a starting point for investigating the causes of this variation within the large bowel.