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The outcome of COVID-19 appears to be influenced by vitamin D status of population. Although epidemiological data indicate that COVID-19 produces more severe symptoms and higher mortality in elderly in comparison to young patients and in men in comparison to women to date sex and age differences in vitamin D status in infected patients have not been evaluated yet. In this study we evaluated the levels of circulating 25(OH)D in patients hospitalized for COVID-19 divided accordingly to their sex and age. We also correlated 25(OH)D levels with patient’s respiratory status (i.e., PaO2/FiO2 ratio) and with sex hormones plasma levels to analyze the potential relationship of these parameters. We found no significant differences in plasma levels of 25(OH)D between pre- and post-menopausal female patients and age matched male patients. Interestingly, the 25(OH)D plasma levels positively correlated to PaO2/FiO2 ratio only in young patients, regardless of their sex. We also found a significantly positive correlation between 17β-estradiol and 25(OH)D in elderly women and between testosterone and 25(OH)D in elderly men, supporting the role of sex hormones in maintaining 25(OH)D levels. In conclusion, we suggest that a synergy between vitamin D and sex hormones could contribute to the age-related outcome of COVID-19.

The aim of this study was to compare survival of resected and unresected patients in a large cohort of patients with metastases to the pancreas from renal cell carcinoma (PM-RCC). Data from 16 Italian centers involved in the treatment of metastatic RCC were retrospectively collected. The Kaplan–Meier and log-rank test methods were used to evaluate overall survival (OS). Clinical variables considered were sex, age, concomitant metastasis to other sites, surgical resection of PM-RCC, and time to PM-RCC occurrence. Overall, 103 consecutive patients with radically resected primary tumors were enrolled in the analysis. PM-RCCs were synchronous in only three patients (3 %). In 56 patients (54 %), the pancreas was the only metastatic site, whereas in the other 47 patients, lung (57 %), lymph nodes (28 %), and liver (21 %) were the most common concomitant metastatic sites. Median time for PM-RCC occurrence was 9.6 years (range 0–24 years) after nephrectomy. Surgical resection of PM-RCC was performed in 44 patients (median OS 103 months), while 59 patients were treated with tyrosine kinase inhibitors (TKIs; median OS 86 months) (p = 0.201). At multivariate analysis, Memorial Sloan Kettering Cancer Center risk group was the only independent prognostic factor. None of the other clinical variables, such as age, sex, pancreatic surgery, or the presence of concomitant metastases, were significantly associated with outcome in PM-RCC patients. The presence of PM-RCC is associated with a long survival, and surgical resection does not improve survival in comparison with TKI therapy. However, surgical resection leads to a percentage of disease-free PM-RCC patients.

This article is a report on different methods of estimation of the number of injection drug users (IDUs) in the Boston standard metropolitan statistical area (SMSA) in 1993. Because the sharing of needles is a means of transmission for HIV, an estimate of the prevalence of injection drug use is essential for acquired immunodeficiency syndrome (AIDS) prevention programs. The data for this study come from the Massachusetts Department of Public Health Bureau of Substance Abuse, the Massachusetts AIDS Surveillance Unit, the Drug Abuse Warning Network (DAWN), the National Household Survey on Drug Abuse: Population Estimates 1993, and the Massachusetts State Police Crime Reporting Unit. The estimates in this study can be assessed with regard to the different time frames that are involved, noting that some estimates are useful only to establish upper or lower bounds. The estimate that best meshes with the findings of this report is that there were between 13,500-16,500 injection drug users in greater Boston and 45,000-60,000 IDUs in Massachusetts in 1993.

Thirty-nine patients received 600 mg/m2 OF MGBG intravenously every week for the treatment of advanced refractory ovarian cancer. Twenty-seven of these received adequate trials, and only two had partial remissions lasting 3 1/2 and 4 months each. Toxicity was substantial, with severe hematologic toxicity in 26%, diarrhea in 22% (severe in 7%), skin rash in 26% (severe in 7%), and vomiting in 70% (severe in 11%). Fatigue, facial paresthesias, and flushing during drug administration were frequent. It appears that MGBG in this dose and schedule has little activity against advanced ovarian cancer.

Purpose: In order to study novel therapeutic approaches taking advantage of natural compounds showing anticancer and anti-proliferative effects, we focused our interest on S-adenosyl-l-methionine, a naturally occurring sulfur-containing nucleoside synthesized from adenosine triphosphate and methionine by methionine adenosyltransferase, and its potential in overcoming drug resistance in colon cancer cells devoid of p53. Results: In the present study, we demonstrated that S-adenosyl-l-methionine overcomes uL3-mediated drug resistance in p53 deleted colon cancer cells. In particular, we demonstrated that S-adenosyl-l-methionine causes cell cycle arrest at the S phase, inhibits autophagy, augments reactive oxygen species, and induces apoptosis in these cancer cells. Conclusions: Results reported in this paper led us to propose S-adenosyl-l-methionine as a potential promising agent for cancer therapy by examining p53 and uL3 profiles in tumors to yield a better clinical outcomes.

We have found that in the secretion of rat anterior prostate, a hydrolyzing activity on GTP is present with a high affinity for the substrate; ATP, GDP, and ADP are not substrates for enzymatic activity. At the same time we have shown that GTP is a negative modulator for the well-known type IV transglutaminase activity present in the prostatic secretion. The hydrolyzing activity on GTP appears to be due to two molecular species: a high-molecular-weight GTPase, having electrophoretical mobility higher than 100 kDa, and a low-molecular-weight GTPase, of about 30 kDa. The two enzymatic activities are associated in the prostatic secretion with the transglutaminase (type IV). We describe an experimental procedure to separate them.

Background Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. Methods Plasma levels of sex hormones (testosterone and 17β-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. Results Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. Conclusions Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring.

Colorectal cancer (CRC) is the second deadliest cancer worldwide despite significant advances in both diagnosis and therapy. The high incidence of CRC and its poor prognosis, partially attributed to multi-drug resistance and antiapoptotic activity of cancer cells, arouse strong interest in the identification and development of new treatments. S-Adenosylmethionine (AdoMet), a natural compound and a nutritional supplement, is well known for its antiproliferative and proapoptotic effects as well as for its potential in overcoming drug resistance in many kinds of human tumors. Here, we report that AdoMet enhanced the antitumor activity of 5-Fluorouracil (5-FU) in HCT 116p53+/+ and in LoVo CRC cells through the inhibition of autophagy, induced by 5-FU as a cell defense mechanism to escape the drug cytotoxicity. Multiple drug resistance is mainly due to the overexpression of drug efflux pumps, such as P-glycoprotein (P-gp). We demonstrate here that AdoMet was able to revert the 5-FU-induced upregulation of P-gp expression and to decrease levels of acetylated NF-κB, the activated form of NF-κB, the major antiapoptotic factor involved in P-gp-related chemoresistance. Overall, our data show that AdoMet, was able to overcome 5-FU chemoresistance in CRC cells by targeting multiple pathways such as autophagy, P-gp expression, and NF-κB signaling activation and provided important implications for the development of new adjuvant therapies to improve CRC treatment and patient outcomes.

The assessment of body composition (BC) can be used to identify malnutrition in patients with Crohn's disease (CD). The aim of this study was to evaluate the nutritional status of CD patients by assessing BC, phase angle (PhA) and muscle strength. Differences in disease duration and medications were also considered.Consecutive adult CD patients aged 18-65 years were enrolled in this cross-sectional study. Disease activity was clinically defined by the Crohn's Disease Activity Index (CDAI) in the active and quiescent phases. All participants underwent anthropometry, BC and handgrip-strength (HGS) measurements; additionally, blood samples were taken. Data from CD patients were also compared with age-, sex- and BMI-matched healthy people.A total of 140 CD patients with a mean age of 38.8 ± 13.9 years and a mean body weight of 64.9 ± 12 kg were recruited and compared to controls. The findings showed that all nutritional parameters, especially PhA and HGS, were lower in CD patients than in controls, and these parameters were substantially impaired as disease activity increased. Active CD patients had a lower body weight and fat mass than both the quiescent and control groups. PhA was negatively correlated with age (r = -0.362; p = 0.000) and CDAI (r = -0.135; p = 0.001) but was positively associated with fat free mass (FFM) (r = 0.443; p = 0.000) and HGS (r = 0.539; p = 0.000). Similarly, serum protein markers were lower in the active CD group than in the quiescent group (p 0.05). Disease duration and medications did not significantly affect nutritional status.BIA-derived PhA is a valid indicator of nutritional status in CD patients, and its values decreased with increasing disease activity. Additionally, small alterations in BC, such as low FFM, and reduced HGS values can be considered markers of nutritional deficiency. Therefore, the assessment of BC should be recommended in clinical practice for screening and monitoring the nutritional status of CD patients.

S-Adenosyl-L-methionine (AdoMet) is the principal methyl donor in transmethylation reactions fundamental to sustaining epigenetic modifications. Over the past decade, AdoMet has been extensively investigated for its anti- proliferative, pro-apoptotic and anti-metastatic roles in several types of human cancer. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide, and is an aggressive type of cancer that is associated with a high recurrence rate, metastasis and poor treatment outcomes. The present study demonstrates, for the first time, to the best of our knowledge, that AdoMet induces cell cycle arrest and inhibits the migratory and invasive ability of two different HNSCC cell lines, oral Cal-33 and laryngeal JHU-SCC-011 cells. In both cell lines, AdoMet attenuated cell cycle progression, decreased the protein level of several cyclins and downregulated the expression of p21 cell cycle inhibitor. Moreover, AdoMet was able to inhibit Cal-33 and JHU-SCC-011 cell migration in a dose-dependent manner after 24 and 48 h, respectively, and also induced a significant reduction in the cell invasive ability, as demonstrated by Matrigel invasion assay monitored by the xCELLigence RTCA system. Western blot analysis of several migration and invasion markers confirmed the inhibitory effects exerted by AdoMet on these processes and highlighted AKT, β-catenin and small mothers against decapentaplegic (SMAD) as the main signaling pathways modulated by AdoMet. The present study also demonstrated that the combination of AdoMet and cisplatin synergistically inhibited HNSCC cell migration. Taken together, these findings demonstrate that the physiological compound, AdoMet, affects the motility and extracellular matrix invasive capability in HNSCC. Thus, AdoMet may prove to be a good candidate for future drug development against metastatic cancer.

The present review summarizes the most recent studies focusing on the synergistic antitumor effect of the physiological methyl donor S-adenosylmethionine (AdoMet) in association with the main drugs used against breast cancer and head and neck squamous cell carcinoma (HNSCC), two highly aggressive and metastatic malignancies. In these two tumors the chemotherapy approach is recommended as the first choice despite the numerous side effects and recurrence of metastasis, so better tolerated treatments are needed to overcome this problem. In this regard, combination therapy with natural compounds, such as AdoMet, a molecule with pleiotropic effects on multiple cellular processes, is emerging as a suitable strategy to achieve synergistic anticancer efficacy. In this context, the analysis of studies conducted in the literature highlighted AdoMet as one of the most effective and promising chemosensitizing agents to be taken into consideration for inclusion in emerging antitumor therapeutic modalities such as nanotechnologies.

Patients with short bowel syndrome (SBS) on long-term home parenteral nutrition (HPN) chronically receive high fluid volumes directly into the right atrium (RA) through the superior vena cava. We retrospectively evaluated cardiac function measured by routine transthoracic echocardiography (TTE) in a population of 26 SBS patients on long-term HPN and compared their data on echocardiograph-derived right heart structure and function, with those of a control group of 26 patients also bearing a central venous catheter (CVC) for other reasons. Results showed that body weight and BMI were significantly higher in the control group. The echocardiographic estimate of RA pressure was higher in HPN patients than in controls (p = 0.01). An increased estimate of RA pressure indicates the need to consider TTE in the follow-up of long-term HPN patients to detect functional impairment early.

OBJECTIVE We hypothesized that the minor allele of the atrial natriuretic peptide (ANP) genetic variant rs5068 is associated with a favorable cardiometabolic phenotype in a general Mediterranean population. RESEARCH DESIGN AND METHODS We genotyped a random sample of the residents of Ventimiglia di Sicilia, Sicily, for rs5068. RESULTS Genotype frequencies of rs5068 are AA, 93.5%; AG, 6.4%; and GG, 0.1%. All subsequent analyses are AA versus AG+GG. After adjusting for age and sex, the minor G allele is associated with lower BMI (estimate [SE]: −1.7 kg/m2 [0.8], P = 0.04). In the AG+GG group, males with HDL cholesterol levels CONCLUSIONS The association between the minor allele of rs5068 and a favorable cardiometabolic phenotype that we previously reported in a U.S. population is now replicated in a Mediterranean population in which the G allele of rs5068 is associated with lower blood pressure, BMI, and prevalence of hypertension and metabolic syndrome. These findings may lead to a diagnostic strategy to assess cardiometabolic risk and lay the foundation for the future development of an ANP or ANP-like therapy for metabolic syndrome.

Background In several human cancers, overexpression of Skp2 (S-phase kinase associated protein 2), which targets p27 for degradation, portends a poorer prognosis. We examined whether Skp2 overexpression is associated with recurrence following radical prostatectomy (RP) for prostate cancer. Methods Immunohistochemical staining for Skp2, p27, and MIB-1 was performed on 109 men with node-negative prostate cancer surgically managed from 1985 – 1996. Associations between the stains were tested and Cox regression was used to determine the association between Skp2 expression and time to biochemical recurrence following RP. Results The 12 tumors (11%) with Skp2 overexpression all had correspondingly low p27 expression ( P = 0.006), and a similar inverse Skp2/p27 relationship was seen in vitro in LNCap cells. Skp2 overexpression in tissue was associated with higher Gleason score ( P = 0.002), more advanced pathological stage ( P = 0.01), and higher MIB-1 index ( P = 0.03), but a more favorable PSA profile ( P = 0.04). Five men received a TURP. Among 104 who received RP, median follow-up was 67 months (range: 0.2 – 218). After adjusting for PSA, pathologic stage, and Gleason score, Skp2 overexpression remained significantly associated with a shorter time to biochemical recurrence (adjusted hazard ratio 4.8 (95% C.I. 1.6 – 14, P = 0.004)). The median time to recurrence with high vs. low Skp2 was 4 vs. 54 months. Conclusions Skp2 overexpression was seen in a significant minority of surgically-managed men and was independently associated with a higher risk of recurrence, raising the possibility that Skp2 could be useful as a prognostic biomarker and as a potential molecular target for novel systemic agents in prostate cancer.

Background:The possible benefit of lifetime physical activity (PA) in reducing prostate cancer incidence and mortality is unclear.Methods:A prospective cohort of 45 887 men aged 45-79 years was followed up from January 1998 to December 2007 for prostate cancer incidence (n2735) and to December 2006 for its subtypes and for fatal (n190) prostate cancer.Results:We observed an inverse association between lifetime (average of age 30 and 50 years, and baseline age) total PA levels and prostate cancer risk. Multivariate-adjusted incidence in the top quartile of lifetime total PA decreased by 16% (95% confidence interval (CI)2-27%) compared with that in the bottom quartile. We also observed an inverse association between average lifetime work or occupational activity and walking or bicycling duration and prostate cancer risk. Compared with men who mostly sit during their main work or occupation, men who sit half of the time experienced a 20% lower risk (95% CI7-31%). The rate ratio linearly decreased by 7% (95% CI1-12%) for total, 8% (95% CI0-16%) for localised and 12% (95% CI2-20%) for advanced prostate cancer for every 30 min per day increment of lifetime walking or bicycling in the range of 30 to 120 min per day.Conclusions:Our results suggest that not sitting for most of the time during work or occupational activity and walking or bicycling more than 30 min per day during adult life is associated with reduced incidence of prostate cancer. © 2009 Cancer Research UK.

Primary neuroendocrine breast carcinomas (NEBCs) are extremely uncommon tumors. The scarcity of data prevents any randomized studies that would establish guidelines or recommendations for the diagnosis and treatment of such a rare entity. • This report describes an interesting case of an NEBC that recurred about 10 years after initial diagnosis, with an impressive long-term disease control using hormonal therapy.

The effect of nontoxic, low concentrations (10 −8 M) of retinoic acid (RA) for a relatively long time (28 days) on a Kirsten ras-virus transformed cell line (Ki-SVC1), derived from the rat seminal vesicle epithelium, was investigated. In these experimental conditions, the cell treatment with RA induced a decrease of the proliferation rate, apoptosis and a marked reduction of both anchorage-independent growth and tumorigenicity. These biological responses were either preceded or associated with important changes in adenylate cyclase/protein kinase C signaling pathways, the activation of important apoptosis-linked genes and a marked decrease of the v-Ki-ras p21 protein. The significance of these findings is discussed.

This paper explores the effects of covariates such as age, gender, chronological time of seroconversion, and mode of virus transmission on the interval between HIV seroconversion and the development of AIDS. For many cohorts which are available to provide information about such effects, both the time of seroconversion and the time of onset of AIDS may be right- or interval-censored. To analyse these doubly-censored data, we propose a method in which we first estimate the marginal distribution of the chronological time of seroconversion and use this distribution to impute the seroconversion time for each subject. Subsequently, we estimate the distribution of induction times conditional on the seroconversion distribution. We apply this technique to a cohort of HIV seropositive subjects recruited from various outpatient facilities throughout Italy and show that age at seroconversion has the greatest effect on induction time.

A novel algorithm to predict incident type 2 diabetes mellitus (iT2DM) is presented considering data from a 20-year prospective study in a Southern Italy population. Eight hundred and fifty-eight out of 1,351 subjects (24-85 years range of age) were selected. Incident type 2 diabetes was diagnosed in 103 patients in a 20-year follow-up. The Finnish Diabetes Risk Score (FINDRISC) and the Framingham Offspring Study simple clinical model (FOS) have been used as reference algorithms. Two custom algorithms have been created using Cox parametric hazard models followed by PROBIT analyses: the first one (VHSRISK) includes all the study subjects and the second one (VHS95RISK) evaluates separately subjects with baseline fasting blood glucose (FBG) above/below 5.2 mmol/L (95 mg/dL). The 44 iT2DM cases below 5.2 mmol/L of baseline FBG were predicted by high LDL cholesterol, metabolic syndrome (ATPIII criteria), BMI > 30 kg/m(2), and high factor VII activity. The 59 cases above the FBG threshold were predicted by FBG classes, hypertension, and age. ROC areas for iT2DM prediction were: FINDRISC = 0.759, FOS = 0.762, VHSRISK = 0.789, and VHS95RISK = 0.803. In a Mediterranean population, the use of a custom generated algorithm evaluating separately low/high FBG subjects improves the prediction of iT2DM in subjects classified at lower risk by common estimation algorithms.

Background and aims Epidemiological prospective data on cardiovascular (CV) events in elderly subjects from Mediterranean populations are lacking. We aimed to investigate 15-year incidence of CV events and to evaluate the association with CV risk factors in an elderly Mediterranean population. Methods and results The population of a small Sicilian village were enrolled, visited and a blood sample was drawn at baseline. CV events were recorded in the 15 years of follow-up. From 1351 subjects (75% of the resident population); 315 were in the age range 65–85 years; 266 subjects free from CV disease were analysed. Seventy-seven CV events were recorded in 73 out of 266 subjects, with a 19.7% rate (in 10 years). Hypertension (HTN) (hazards ratio = 2.1) and diabetes mellitus (DM) (hazards ratio = 1.8) were independently associated with CV events. Subjects with both DM and HTN showed a lower survival free of CV events compared to those with DM or HTN. Conclusions In a 15-year follow-up of an elderly Mediterranean population free from CV disease, diabetes mellitus and hypertension were related to CV events. The control of risk factors in the elderly needs to be reinforced to achieve better results in terms of CV prevention.

We evaluated the hypothesis that higher levels of total daily physical activity can eliminate the increased mortality rate associated with overweight and obesity.Population-based prospective cohort study.Central Sweden.A total of 37,633 men at baseline 45-79 years of age and free of known cancer and cardiovascular disease and diabetes completed a self-administered life-style questionnaire, which included questions on body-mass index (BMI) and physical activity. During 9.7 years of follow-up, we identified a total of 4086 deaths.Mortality rate ratios (RRs).Compared to men who were lean (BMI25 kg m(-2)) and active (top tertile of total physical activity level) the multivariable adjusted RRs (95% confidence interval) of death from all causes were 1.44 (1.11-1.86) for obese (BMIor = 30 kg m(-2)) and active men, 1.54 (1.34-1.77) for lean (BMI25 kg m(-2)) but inactive (bottom tertile) men, and 1.81 (1.48-2.23) for obese-inactive men. After excluding the first 3 years of follow-up, current and former smokers, those who had lost weight from age 20 years to age at baseline, and heavy manual workers, the adjusted RRs of death from all causes were 1.65 (1.20-2.27) for overweight-to-obese and active men, 2.15 (1.59-2.91) for lean-inactive men, and 2.04 (1.52-2.74) for overweight-to-obese and inactive men compared to lean-active men.We conclude that both overweight and physical inactivity are important predictors of mortality. Our findings do not support the hypothesis that a higher level of physical activity compensates the excess mortality associated with overweight and obesity.

Aim of this study was to assess the validity of a short self-administered physical activity questionnaire, intended to measure past year total daily physical activity, by comparison with activity records and accelerometers. Over a 1-year period, data from a questionnaire, 7-day activity records and accelerometers were obtained from a subset of 116 women between the ages of 56 and 75 years from the population-based Swedish Mammography Cohort. We estimated concordance correlations as measure of validity, deattenuated for intraindividual variation in the reference method. Deattenuated concordance correlations comparing total daily activity measured by the questionnaire with the accelerometers and the records were 0.38 (95% CI: 0.22-0.54) and 0.64 (95% CI: 0.45-0.83), respectively. Validity of leisure-time activity (walking/bicycling and exercise) and inactivity (watching TV/reading) estimates comparing the records with the questionnaire were 0.42 (95% CI: 0.22-0.62) and 0.52 (95% CI: 0.36-0.69), respectively. These data indicate that the average past year total physical activity, leisure-time activity and inactivity can be estimated with a reasonable validity using our short self-administered questionnaire. © 2008 Springer Science+Business Media B.V.

Few studies have evaluated the reliability of a self-administered current and historical physical activity questionnaire (PAQ) among middle-aged and elderly women. We evaluated the reliability of a self-administered PAQ designed to assess total (24 h) current and historical physical activity at age 15, 30, and 50 years, which was completed by a subgroup of 303 women aged 56-75 years from the Swedish Mammography Cohort (SMC). Total physical activity covered occupational and household activity as well as walking/bicycling, exercise, and inactivity (sitting watching TV/reading). Reliabilities (1-year test-retest) of continuous activity measures in metabolic equivalents were evaluated using an intraclass correlation coefficient (ICC); classification consistency was evaluated using sensitivity and specificity statistics. The ICC for total current physical activity was 0.69; for specific types of activities the ICC ranged from 0.49 to 0.59; for historical physical activity, the reliabilities for total activity ranged from 0.75 for age 50 to 0.81 for age 30 years, being substantial for occupational activities (ICC = 0.73-0.75), and fair to moderate for inactivity (ICC = 0.31-0.60). These data indicate that the PAQ used in the SMC is a satisfactory and reproducible measure of current and historical physical activity, for total as well as for different types of activities.

The aim of this study was to evaluate the cardiovascular (CV) risk due to the metabolic syndrome in a 15-year prospective study of a Sicilian population. In the Mediterranean area obesity is highly prevalent, but epidemiological data on the metabolic syndrome are limited. Methods and results: Among the 1351 subjects enrolled in the “Ventimiglia di Sicilia” epidemiological project, we selected 687 subjects between 35 and 75 years of age; baseline parameters were assessed and subjects have been followed for 15 years recording CV events, total and cardiovascular mortality. The metabolic syndrome was defined according to both the Adult Treatment Panel III and the International Diabetes Federation criteria. Metabolic syndrome (ATPIII criteria)was significantly (p < 0.00001) more prevalent inwomen (31.5%) than in men (12.4%). The metabolic syndrome increased the risk of CV events with a hazard ratio of 1.9 (confidence interval CI; 1.46–2.46). Using a Cox proportional hazards estimation model, the survival curve of subjects with metabolic syndrome and normal fasting glucose did not significantly differ from the curve of subjects with metabolic syndrome and impaired fasting glucose (IFG). Conclusions: In a 15-year follow-up the metabolic syndrome is predictive of CV events regardless of the presence of IFG or diabetes mellitus.

Introduction: Atrial natriuretic peptide (ANP) possesses cardiorenal protective properties including natriuresis, aldosterone suppression and vasodilation. Importantly, ANP also exerts lipolytic effects in vitro and in vivo. Previous studies reported that the ANP genetic variant rs5068 is associated with increased plasma levels of ANP, lower blood pressure values, and reduced risk of hypertension. We recently reported that in a random sample of the general population from Olmsted County, MN the G allele of rs5068 was associated with increased levels of ANP, lower blood pressure and BMI, waist circumference, reduced prevalence of obesity and metabolic syndrome. To date, these associations have not been replicated. Hypothesis: The minor allele of rs5068 is associated with a favorable cardiometabolic phenotype in a randomly selected Mediterranean population. Methods: We genotyped a well characterized random sample of the residents of Ventimiglia di Sicilia, a small town in Sicily. Results: Genotype frequencies of rs5068 were AA: 93.5%, AG: 6.4%, and GG: 0.1%. All subsequent analyses are AA vs AG+GG. After adjusting for age and gender, the minor G allele was associated with lower systolic (120624 vs 126621 mmHg, p50.003) and diastolic (72610 vs 76610 mmHg, p50.03) blood pressure and lower BMI (26.764.9 vs 28.265.7 kg/m2, p50.04). Male subjects presenting HDL cholesterol plasma levels!40 mg/dL were less frequent in the AG+GG group (17% vs 27%,p50.05). Importantly, the G allele was significantly associated with a lower prevalence of metabolic syndrome (19% vs 32%, p50.02). Conclusions: The association between the minor allele of rs5068 and a favorable cardiometabolic phenotype, that we previously showed in a US population, is now replicated in a Mediterranean population in which the G allele of rs5068 is associated with lower blood pressure values, BMI, and prevalence of metabolic syndrome. These findings may lead to a diagnostic strategy to assess cardiometabolic risk and also lay the foundation for future development of an ANP or ANP-like therapy for metabolic syndrome.

Several lines of evidence indicate that neutrophils act nonspecifically against tumor cells. The correlation between tumor-infiltrating neutrophils (TINs) and clinicopathological features remains unclear and deserves to be investigated. To analyze the prognostic influence of TINs in gastric carcinoma, the authors selected 273 patients with advanced gastric carcinoma who underwent gastrectomy at Cremona Hospital (Lombardia, Italy) between 1990 and 1995 and followed them for a period of 5 years. The number of TINs was assessed in a semiquantitative manner using the mean value of 20 nonoverlapping high-power fields (magnification, 400x; 0.08 mm(2)). The patients were divided into two groups: patients with a moderate or extensive amount of TINs (n = 76; >10 TINs per 20 high-power fields) and patients with a minor amount of TINs (n = 197

OBJECTIVE: We investigated the prevalence of overweight and obesity and their relationships with the main cardiovascular risk factors in the population of Ventimiglia di Sicilia, a rural village in Southern Italy characterized by low cholesterol levels and by a low incidence of early coronary heart disease mortality. We related all deaths to body weight and fat distribution during an 8 y follow-up. DESIGN: Cross-sectional and prospective observational study. SUBJECTS: A total of 835 free-living individuals, 363 males and 472 females, of age between 20 and 69 y. MEASUREMENTS: In all participants body weight, waist-to-hip ratio (WHR), cardiovascular risk factors and plasma lipids were measured. During the follow-up, total and cardiovascular deaths were registered. RESULTS: We found a high overall prevalence of subjects with overweight or obesity (respectively 45.0% and 27.7%), with great differences among classes of age. As expected, body weight and fat distribution were associated with diabetes, hypertension, dyslipidemia and with a worsening of lipid profile. During the follow-up we registered 37 total and 11 cardiovascular deaths. All-cause and cardiovascular mortality risks were, respectively, 1.64 (95% CI 0.65-4.15) and 2.71 (95% CI 0.29-25.26) in subjects with a body mass index (BMI) of 27-29.99 kg/m2 and 2.45 (95% CI 1.03-5.87) and 5.36 (95% CI 1.41-62.01) in subjects with a BMI of ≥ 30 kg/m2 in comparison with participants with a BMI of < 27 kg/m2, and 3.48 (95% CI 1.46-8.30) and 4.55 (95% CI 1.12-18.40) in subjects with a WHR higher than the median in comparison with individuals with a WHR lower than the median. CONCLUSION: The Ventimiglia di Sicilia Study highlights the great importance of overweight and obesity as a public health issue in a rural population and indicates that it is necessary to consider the impact of body weight and fat distribution on both total and CHD mortality.

The effect of phosphorylation on the hormone-binding capacity of the estrogen receptor (ER) was investigated in hormone-dependent (HD) and hormone-independent (HI) mammary carcinomas of GR mice. Tumor cytosols were incubated with ATP under conditions previously used to study the tyrosine kinase which confers hormone binding to phosphatase-treated or in vitro-synthesized ER. The ATP-dependent increases in hormone-binding capacity of 8 out of 20 HI tumors ranged from values of 23 to 124 fmol/mg cytosol protein. The enhancement by ATP of hormone binding to ER was significantly less marked in HD and HR tumors than in HI tumors. In only 3 out of 13 HD and HR tumors was an increase ranging from 15 to 20 fmol/mg protein detected. Analysis by Scatchard plot of estradiol binding to ER showed that cytosol incubation of HI tumors with ATP markedly increased the hormone binding without any change in affinity. The data suggest that ER of HI tumors is less phosphorylated in vivo than the ER of HD/HR tumors, so that the receptor of HI tumors is more susceptible to γ32P-ATP phosphorylation and ATP-induced hormone binding in vitro. Western blot of ER with antiphosphotyrosine antibody showed that, in HI tumors, the large ATP-induced increase in hormone binding to ER was associated with phosphorylation on tyrosine of the receptor itself. Our findings indicate that the process of activation-inactivation of binding through tyrosine-phosphorylation/ phosphotyrosine-dephosphorylation of ER observed in estrogen target tissues is altered in some HI mammary tumors. © 1992 Wifey-Liss, Inc.

Intraocular pressure (IOP) in a healthy population residing in the urban area of Naples, Italy was measured. The IOP was recorded in the early morning. A total of 751 subjects (367 men and 384 women) (1502 eyes) was examined twice on two different days using a Goldmann tonometer mounted on a Haag-Streit slitlamp. Age ranged from 6 to 89 years. We found a slight and not significant IOP increase with age and that the age-related IOP increase was more evident in women.

Information on correlates of total physical activity (PA) levels among middle-aged and elderly women is limited. This article aims to investigate whether total daily PA levels are associated with age, body mass index, smoking, drinking status, and sociodemographic factors. In a cross-sectional study of 38,988 women between the ages of 48 and 83 years residing in central Sweden, information on PA, weight, height, smoking, drinking, and sociodemographic factors was collected through a self-administered questionnaire. Total daily PA levels were measured as metabolic equivalents (MET-h/day). Odds ratios (OR) and 95% confidence intervals (CI) were estimated by ordinal logistic regression models. We observed decreasing level of total PA with increasing age (for 5-year increase: OR = 0.87; 95% CI: 0.85–0.89) and body mass index (for 5-unit, kg/m2, increase: OR = 0.81; 95% CI: 0.79–0.84). Multivariable adjusted correlates of total PA level were smoking (current vs. never: OR = 0.83; 95% CI: 0.79–0.88), drinking (current vs. never: OR = 0.88; 95% CI: 0.82–0.94), educational level (university vs. primary: OR = 0.54; 95% CI: 0.51–0.58), employment status (housewife vs. full-work: OR = 2.59; 95% CI: 2.25–2.98), and childhood environment (city vs. countryside: OR = 0.62; 95% CI: 0.59–0.65). In the present investigation, among middle-aged and elderly women, the likelihood of engaging in higher total daily PA levels decreased with age, body mass index, educational level, smoking, drinking, and growing up in urban places.

In whole rat uterus incubated in the presence of [ 32 P]orthophosphate the oestradiol receptor is [ 32 P]phosphorylated on tyrosine. This finding follows our previous observation that in vitro this receptor can be phosphorylated on tyrosine by a uterus kinase that endows the receptor with oestradiol-binding activity. The calf uterus oestradiol receptor interacts with high affinity with 2G8 and 1G2 antiphosphotyrosine antibodies coupled to Sepharose ( K d values of 0.28 and 1.1 nM, respectively). The interaction with 2G8 antibody has been exploited to purify the oestradiol receptor. This interaction disappears after inactivation of the oestradiol receptor by the nuclear phosphatase that hydrolyses phosphotyrosine of the receptor. This fact substantiates the evidence that the oestradiol receptor in uterus is phosphorylated on tyrosine and that this phosphorylation is required for hormone binding to the receptor. The rat liver glucocorticoid receptor also interacts with high affinity with 2G8 antiphosphotyrosine antibody coupled to Sepharose ( K d value of 0.21 nM). This receptor has been purified by using in sequence heparin-Sepharose and antiphosphotyrosine antibody-Sepharose.

Knowledge of alimentary habits among populations permits a better definition of appropriate public health interventions. We designed the epidemiological project "Ventimiglia di Sicilia" to characterize the risk profile in a rural village with low total cholesterol levels and low early cardiovascular mortality but with a large prevalence of overweight and obesity, which previously have been significantly associated with total mortality.488 individuals of age 20 to 69 years were included in the dietary survey conducted by a seven-day food record.Alimentary habits were characterized by high consumption of total and complex carbohydrates (respectively 52.5 +/- 7.6% and 46.6 +/- 8.2% of daily energy) and by a low cholesterol intake (92.5 +/- 35.0 mg/1000 kcal/day). Fat intake was 34.7 +/- 7.7% of daily energy due to a higher consumption of monounsaturated fats in respect to saturated fats (respectively 20.5 +/- 5.1% and 10.2 +/- 2.9% of daily energy). In particular, in this population there was a large consumption of bread, pasta, fresh vegetables, olive oil and fruits. We also observed an excess of total calories (about 2900 kcal/day in men and 2100 kcal/day in women) not balanced by a high degree of physical activity levels. Furthermore we found a significant higher total and saturated fat consumption in the youngest individuals and in people with higher educational levels.Dietary habits of Ventimiglia di Sicilia still follow the nutritional characteristics typical of the Mediterranean diet. The high total calorie intake indicates a quantitative more than qualitative problem, which may account the large prevalence of overweight and obesity and may represent a public health issue that needs to be corrected in such a rural population.

Because endurance exercise causes release of mediators and growth factors active on the bone marrow, we asked whether it might affect circulating hematopoietic progenitor cells (HPCs) in amateur runners [ n = 16, age: 41.8 ± 13.5 (SD) yr, training: 93.8 ± 31.8 km/wk] compared with sedentary controls ( n = 9, age: 39.4 ± 10.2 yr). HPCs, plasma cortisol, interleukin (IL)-6, granulocyte colony-stimulating factor (G-CSF), and the growth factor fms-like tyrosine kinase-3 (flt3)-ligand were measured at rest and after a marathon (M; n = 8) or half-marathon (HM; n = 8). Circulating HPC counts (i.e., CD34+cells and their subpopulations) were three- to fourfold higher in runners than in controls at baseline. They were unaffected by HM or M acutely but decreased the morning postrace. Baseline cortisol, flt3-ligand, IL-6, and G-CSF levels were similar in runners and controls. IL-6 and G-CSF increased to higher levels after M compared with HM, whereas cortisol and flt3-ligand increased similarly postrace. Our data suggest that increased HPCs reflect an adaptation response to recurrent, exercise-associated release of neutrophils and stress and inflammatory mediators, indicating modulation of bone marrow activity by habitual running.