Expression of pro-angiogenic factors as potential biomarkers in experimental models of colon cancer.

PURPOSE: RAS mutational status in colorectal cancer (CRC) represents a predictive biomarker of response to anti-EGFR therapy, but to date it cannot be considered an appropriate biomarker of response to anti-VEGF therapy. To elucidate the function of K-Ras in promoting angiogenesis, the effect of conditioned media from KRAS mutated and wild type colon cancer cell lines on HUVECs tubule formation ability and the correspondent production of pro-angiogenic factors have been evaluated by a specific ELISA assay. METHODS: Ras-activated signaling pathways were compared by western blot analysis and RTq-PCR. In addition, VEGF, IL-8, bFGF and HIF-1α expression was determined in K-RAS silenced cells. Furthermore, we conducted an observational study in a cohort of RAS mutated metastatic CRC patients, treated with first-line bevacizumab-based regimens, evaluating VEGF-A and IL-8 plasma levels at baseline, and during treatment. RESULTS: K-RAS promotes VEGF production by cancer cell lines. At the transcriptional level, this is reflected to a K-RAS dependent HIF-1α over-expression. Moreover, the HIF-1α, VEGF and FGF expression inhibition in KRAS knocked cells confirmed these results. Within the clinical part, no statistically significant correlation has been found between progression-free survival (PFS) and VEGF-A/IL-8 levels, but we cannot exclude that these biomarkers could be further investigated as predictive or prognostic biomarkers in this setting. CONCLUSION: Our study confirmed the direct involvement of K-Ras in promoting angiogenesis into colon cancer cell lines.

Geographical and temporal changes of anthropometric traits in historical Yemen.

This study investigates secular changes of anthropometric variables among four geographic groups in historical Yemen, to evaluate possible regional differences in the evolution of living standards. Nineteen somatic and cephalic measures collected by Coon in 1939, and 8 anthropometric indices in 1244 Yemenite adult males were analyzed. The individuals were divided into 10-year age groups. Within-group variations were tested by One-way ANCOVA (age as covariate). ANCOVA (controlling for age), and Forward stepwise discriminant analysis were used to evaluate and represent regional differences. ANCOVA and discriminant analysis confirmed and enhanced previous findings. At the time, the Yemenite population presented high intergroup heterogeneity. The highest mean values of height at all ages were found in the "mountain" region, which is characterized by very fertile soils and where, nowadays, most of the cereals and pulses are grown and where most livestock is raised. Within-group variations were limited and generally inconsistent in all geographic regions and concern vertical dimensions, but mean values of height never differed. The prolonged internal isolation of these groups resulted in significant regional morphometric differentiation. The main evidence comes from height which suggests that socioeconomic factors have played a role. Nevertheless, the possible better living conditions experienced by the "mountain" group, with the highest mean values of stature in all periods, did not allow the secular trend to take place in that region, too.

Microgeographic differentiation in historical Yemen inferred by morphometric distances.

This study analyzed the variations in space of 8 body dimensions and 11 measures of the head of 1,244 adult Yemenite males, collected in 1933/34 by Coon in Yemen and in Hadhramawt. The aim was to evaluate the presence of geographic microdifferentiation of the populations settled in the different regions of Yemen at the time. Coon sub-divided the sample into six geographical areas according to birthplace and ethnicity of the individuals: Tihamah, the Western Mountains, the Central Plateau, the South Coast, the Eastern Mountains, and Hadhramawt. The results of ANCOVA (age as covariate) show that the observed differences of all variables among the six groups were highly statistically significant. Tukey's post-hoc test reveals higher statistically significant differences among four main groups: (1) Tihamah; (2) the Western Mountains and Central Plateau; (3) the Eastern Mountains; and (4) the Southern Coast and Hadhramawt. Multiple discriminant analysis carried out using only the data of the 11 measures of the head, the more "genetically" determined variables, confirmed these differences. Indeed, the first canonical variate well separates the groups with the Tihamah, Southern Coast and Hadhramawt on the one side and the Eastern Mountains, Western Mountains and Central Plateau on the other. The second canonical variate separates the Tihamah, Western Mountains and Central Plateau from the Eastern Mountains, Southern Coast and Hadhramawt. In conclusion, the Yemenite population seems to be composed of three morphologically distinct groups and an Eastern Mountains group which is positioned between the group formed by the Southern Coast and Hadhramawt and the Western Mountains and Central Plateau group. The Tihamah is the most distant from all the other groups. These differences are probably due to the presence/absence of geographical and cultural barriers that have favored/blocked the gene flow over the years. Indeed, the entire coastal bell, through the centuries, has constituted one of the principal commercial routes between the East, Africa, and the eastern Mediterranean, while the high inland mountains have isolated the remaining communities. This data is also confirmed by genetic studies. Finally, the average height (162.6 cm) of the global Yemenite population, compared to data from the other six middle-eastern Arab countries and Egypt, was found to be 3-6 cm less. This characteristic will be further studied, analyzing variations in average height according to the different age classes in order to evaluate any possible secular changes.

Morphometric distances among five ethnic groups and evaluation of the secular trend in historical Libya.

This study analysed the variations, both in space and time, of 10 body dimensions and 2 anthropometric indexes of 745 adult males belonging to 5 ethnic groups of historical Lybia (el-Haràbi, el-Baraghìts, Marabtìn, Oases inhabitants and Tuareg). The data were collected in the years 1928 and 1932 by Puccioni and Cipriani, two Italian anthropologists. The aim was to reconstruct the biological history of Libya at the time, and thus contribute to the ongoing debate on the evolution of the biological standard of living in developing Countries. The subjects were analysed by ethnicity and by 10-year age groups, after adjusting for age. The results of ANCOVA and Tukey's post-hoc test show that among and between groups there are statistical significant differences overall for armspan, height, head breadth, bizygomatic breadth, biiliac breadth/height and head breadth/head length indexes. By means of the cluster analysis, the el-Haràbi, el-Baraghìts and Marabtìn groups cluster together, whereas the Tuareg and Oases inhabitants cluster separately one from the other and both from the other three ethnic groups. Within-group variations are not very marked in all ethnicities. In general, there is the tendency, not statistically significant, to the reduction and/or stasis of body dimensions from the older to the younger, and the differences are greater among the older than the younger age classes. In conclusion, it can be argued that these groups, all different culturally and geographically, were following the same tendency of stasis of the secular trend of the body dimensions considered in this study, and such stasis persisted since, at least, the last twenty years of the 19th century, when the older were born.

Are changes in body dimensions of adult females from Italy (Sardinia and Latium) related to secular trend?

This paper presents secular changes in height, weight, sitting height, relative sitting height, BMI and estimated lower limb length in two samples of Italian adult females from Sardinia (Cagliari) and Latium (Rieti). The samples consist of 579 healthy women from the province of Cagliari and 138 from the town of Rieti, aged 20.0-39.9 years, measured in the period 2003-2006. The women were divided into four 5-year age groups. The anthropometric variables were considered according to different socioeconomic status (SES) in the Cagliari sample, while the Rieti sample was considered as a whole, as the SES was homogeneous. ANOVA results suggest that the secular trend was very slow or had come to a halt in the Rieti sample but continues in the Cagliari sample, as shown by the statistically significant differences for estimated lower limb length (p

Seasonality of marriages in sardinian pastoral and agricultural communities in the nineteenth century.

The study of marriage seasonality of populations with different socioeconomic backgrounds may contribute to the better understanding their reproductive behaviours. This study analyses the monthly distribution of marriages in the 19th century in four agricultural villages and four pastoral villages on the island of Sardinia (Italy). The data were derived from 7340 marriage acts (3571 for the four agricultural villages and 3769 for the four pastoral villages). The aim is to ascertain whether the Sardinian agricultural and pastoral communities followed the matrimonial models reported for contemporary Italy and Europe and whether there was a change in the monthly distribution of marriages between the two halves of the 19th century. The results suggest that the marriage seasonality of the Sardinian farmers and shepherds was very similar to the patterns shown in the 19th century by Italian and European agricultural and pastoral communities. The Sardinian farmers preferred to marry in autumn-winter, while the Sardinian shepherds had a very high concentration of marriages in summer-autumn. Both communities avoided marriages in the Advent and Easter periods and in the month of May (dedicated to the Virgin Mary), and the farmers also in August (also dedicated to the Virgin Mary). Despite a certain seasonal stability, there was a significant change in the monthly distribution of marriages between the two halves of the 19th century in both the agricultural and pastoral communities, probably due to a series of laws that transformed the centuries-old socioeconomic system of Sardinia in the second half of the century.

Anthropometric variables of a sample of Italian adults and their relation to physical activity.

The increasing diffusion of fitness centers in Italy is a response to the growing awareness of the serious health risks of a sedentary lifestyle. In the present study, we defined the anthropological profile of members of a sports club in Rieti (Latium, Central Italy) and evaluated the effects of constant physical activity on their somatic characteristics. Data from 335 healthy males and females were used. We analyzed 36 anthropometric measures in two large age classes (20-39 years and 40 years and over). In a subsample of 40 volunteers, the measures were recorded again after about 5 months (on average). Student's t-test showed significant differences (p = 0.05) between the two age classes for 8 variables in the males and 11 variables in the females and highly significant differences (p = 0.001) for 6 variables in the males and 4 in the females. In the subjects measured a second time, the paired t-test showed significant differences for 12 parameters in the males and 7 parameters in the females and highly significant differences for 7 variables in the males and 10 in the females. The differences between the two age classes in both sexes confirm the presence of both the secular trend and significant morphological changes due to aging. The significant decreases of all health-related anthropometric measurements after an average of 5 months of physical activity in both sexes demonstrate that the beneficial effects of regular physical activity become apparent after only a few months.

Secular changes in human biological variables in Western countries: an updated review and synthesis.

This paper provides a review of the recent literature on some aspects of secular trends in Western countries. In particular, we discuss height variation, mainly on the basis of conscript data. There are still large height differences between European countries, and there is a marked trend for the tallest conscripts to be in northern Europe and the shortest ones in the southern part of the continent. The secular trend in adult height has come to a halt in northern Europe and Italy, while it is still in progress in Belgium, Spain and Portugal. The secular trend in height mainly depends on the increase of lower limb length. Obesity is now epidemic in Western countries, the USA population being the most affected. There is also a progressive anticipation of all the signs of puberty, namely age at menarche, appearance and development of the breasts, genitals and pubic and axillary hair, although there is ethnic/population variability in this regard. A tendency to later onset of menopause has also been recorded. Regarding secular trends in sport, there has been a progressive selection of athletes with larger body dimensions. Finally, the authors provide suggestions for future fruitful directions of the research of the secular trend in human biology.

Comparison of self-reported and measured height and weight: implications for obesity research among young adults.

BACKGROUND: The use of self-reported data in epidemiological surveys leads to misclassification of the prevalence of obesity as the participants overestimate or underestimate height, weight and/or both. Such misclassifications vary according to gender, age, status and ethnicity. OBJECTIVES: To estimate on a sample of youth of both sexes (1) the difference between self-reported data and measured height and weight and (2) the extent of misclassification of BMI deriving from such differences. METHODS: Self-reporting in questionnaires and subsequent measurements of height and weight conducted by trained personnel. The mean values and the BMIs were calculated. RESULTS: Both sexes overestimate height (2.1 and 2.8cm for males and females, respectively), and underestimate weight (1.5 and 1.9kg for males and females, respectively). Consequently the BMI is underestimated (1.1 and 1.5 points for males and females, respectively). The classification of BMI from self-reported data shows underestimation of overweight in both sexes (8 percentage points) and of obese males (3.3 percentage points), an overestimation of normal weight (12.2 and 4.3 percentage points for males and females, respectively) and an excessive underweight in the girls (4.3 percentage points). CONCLUSIONS: There is a difference between self-reported and measured data and self-reported biases are reflected in the classification of the participants in the 4 categories of BMI.

Height and BMI of Italian immigrants to the USA, 1908-1970.

We analyze self-reported anthropometric data pertaining to 2140 adults who emigrated to the United States, mainly from southern Italy, between 1908-1928 and 1960-1970. The mean height of immigrant men was 165.5 cm: they were taller than contemporary southern Italian men by 0.5-7.3 cm in different periods. The mean height of the Italian immigrant women born before 1952 was 157.6 cm, less than the national average. At the end of the 1990s, national women average height was 162 cm, 159.5 cm for southern women. There were age-related increases of weight and BMI: overweight was more prevalent in the 40-49 years age category. In the male sample, the mean values of BMI were within the overweight range in all age classes. The prevalence of obesity was higher in the male sample than among US men, whereas it was virtually identical in the women's sample and much higher than the values reported for several European countries for the period 1970-1980.

Age at menarche and age of onset of pubertal characteristics in 6-14-year-old girls from the Province of L'Aquila (Abruzzo, Italy).

The present study is part of a research project on growth models of children in an area of central-southern Italy. It analyzes the phases of pubertal breast development (BD) in 397 girls, pubic hair development (PHD) in 399 girls, and menarche in 583 girls from 6-14 years old. The status quo method was used to evaluate the age at menarche. Probit analysis was used to analyze the data for all three variables. The onset of BD and PHD (Tanner stage 2) occurs at age 7 in 6.1% of girls. Passage to stage 3 of one or both secondary sexual characteristics occurs at age 10 in 8.5% of girls. Comparison with data from the United States shows higher percentages of American white girls in stage 2 (or greater) of both characteristics at any age. The mean (median) age of onset (Tanner stage 2) of BD or PHD or both of them is 9.96 years. The passage to stage 3 occurs at age 12.36 for BD (95% confidence interval: 1.36 years) and at age 12.10 for PHD (95% confidence interval: 0.51 years). The mean age at menarche is 12.55 years, in general agreement with other values found in Italy. Sexual maturation at any considered stage for both pubertal characteristics is generally in line with literature data concerning other Mediterranean and industrialized countries or countries in which the demographic transition is in an advanced phase. It does not show a significant earlier onset. The evidence emerging from the general project suggests that the secular trend is still in progress in this region of Italy.