Radiosurgery and stereotactic irradiation of multiple and contiguous brain metastases: A practical proposal of dose prescription methods and a literature review.

PURPOSE: In literature, there are no guidelines on how to prescribe dose in the case of radiosurgery (SRS) or stereotactic irradiation of multiple and adjacent BM. Aim of this work is to furnish practical proposals of dosimetric methods for multiple neighboring BM, and to make a literature review about the SRS treatment of multiple BM, comparing radiotherapy techniques on the basis of different dosimetric parameters. MATERIALS AND METHODS: A theoretical proposal of dosimetric approaches to prescribe dose in case of multiple contiguous BM is done. A literature review between 2010 and 2020 was performed on MEDLINE and Cochrane databases according to the PRISMA methodology, with the following keywords dose prescription, radiosurgery, multiple BM. Papers not reporting dosimetric solutions to irradiate multiple BM were excluded. RESULTS: Only one article in the literature reports a practical modality of dose prescription for multiple adjacent BM. Thus, we proposed other five practical solutions to prescribe radiation dose in case of two or more neighboring BM, describing advantages and drawbacks of each method in terms of different dosimetric parameters. The literature review about dosimetric solutions to irradiate multiple BM led to 56 titles; 14 articles met the chosen criteria and we reported their results in terms of dosimetric indexes and low doses to the normal brain tissue. CONCLUSIONS: The six dosimetric approaches here described can be used by physicians for multiple contiguous BM, depending on the clinical situation. These methods may be applied in clinical studies to better evaluate their usefulness in practice.

Dermoscopy of basal cell carcinoma.

Dermoscopy is widely used in dermatological practice. The method increases the accuracy of basal cell carcinoma (BCC) detection. Pigmented and nonpigmented variants of basal cell carcinoma present different dermoscopic features. Specific dermoscopy criteria have been recognized in different subtypes of BCC. Differentiation of superficial BCC from other subtypes is the most important issue, as it may determine further management decisions.

Socioeconomic inequalities in childhood overweight: heterogeneity across five countries in the WHO European Childhood Obesity Surveillance Initiative (COSI-2008).

BACKGROUND: Excess risk of childhood overweight and obesity occurring in socioeconomically disadvantaged families has been demonstrated in numerous studies from high-income regions, including Europe. It is well known that socioeconomic characteristics such as parental education, income and occupation are etiologically relevant to childhood obesity. However, in the pan-European setting, there is reason to believe that inequalities in childhood weight status may vary among countries as a function of differing degrees of socioeconomic development and equity. SUBJECTS AND METHODS: In this cross-sectional study, we have examined socioeconomic differences in childhood obesity in different parts of the European region using nationally representative data from Bulgaria, the Czech Republic, Lithuania, Portugal and Sweden that were collected in 2008 during the first round of the World Health Organization (WHO) European Childhood Obesity Surveillance Initiative. RESULTS: Heterogeneity in the association between parental socioeconomic indicators and childhood overweight or obesity was clearly observed across the five countries studied. Positive as well as negative associations were observed between parental socioeconomic indicators and childhood overweight, with statistically significant interactions between country and parental indicators. CONCLUSIONS: These findings have public health implications for the WHO European Region and underscore the necessity to continue documenting socioeconomic inequalities in obesity in all countries through international surveillance efforts in countries with diverse geographic, social and economic environments. This is a prerequisite for universal as well as targeted preventive actions.

Validation of the Portuguese self-administered computerised 24-hour dietary recall among second-, third- and fourth-grade children.

BACKGROUND: Current methods for assessing children's dietary intake, such as interviewer-administered 24-h dietary recall (24-h DR), are time consuming and resource intensive. Self-administered instruments offer a low-cost diet assessment method for use with children. The present study assessed the validity of the Portuguese self-administered, computerised, 24-h DR (PAC24) against the observation of school lunch. METHODS: Forty-one, 7-10-year-old children from two elementary schools, in Lisbon, were observed during school lunch followed by completion of the PAC24 the next day. Accuracy for reporting items was measured in terms of matches, intrusions and omissions; accuracy for reporting amounts was measured in terms of arithmetic and absolute differences for matches and amounts for omissions and intrusions; and accuracy for reporting items and amounts combined was measured in terms of total inaccuracy. The ratio of the estimated weight of food consumed with the actual weight consumed was calculated along with the limits of agreement using the method of Bland and Altman. RESULTS: Comparison of PAC24 against observations at the food level resulted in values of 67.0% for matches, 11.5% for intrusions and 21.5% for omissions. The mean for total inaccuracy was 3.44 servings. For amounts, accuracy was high for matches (-0.17 and 0.23 servings for arithmetic and absolute differences, respectively) and lower for omissions (0.61 servings) and intrusions (0.55 servings). PAC24 was found to under-estimate the weight of food on average by 32% of actual intake. CONCLUSIONS: PAC24 is a lower-burden procedure for both respondents and researchers and, with slight modification, comprises a promising method for assessing diet among children.

WHO European Childhood Obesity Surveillance Initiative 2008: weight, height and body mass index in 6-9-year-old children.

UNLABELLED: What is already known about this subject Overweight and obesity prevalence estimates among children based on International Obesity Task Force definitions are substantially lower than estimates based on World Health Organization definitions. Presence of a north-south gradient with the highest level of overweight found in southern European countries. Intercountry comparisons of overweight and obesity in primary-school children in Europe based on measured data lack a similar data collection protocol. What this study adds Unique dataset on overweight and obesity based on measured weights and heights in 6-9-year-old children from 12 European countries using a harmonized surveillance methodology. Because of the use of a consistent data collection protocol, it is possible to perform valid multiple comparisons between countries. It demonstrates wide variations in overweight and obesity prevalence estimates among primary-school children between European countries and regions. BACKGROUND: Nutritional surveillance in school-age children, using measured weight and height, is not common in the European Region of the World Health Organization (WHO). The WHO Regional Office for Europe has therefore initiated the WHO European Childhood Obesity Surveillance Initiative. OBJECTIVE: To present the anthropometric results of data collected in 2007/2008 and to investigate whether there exist differences across countries and between the sexes. METHODS: Weight and height were measured in 6-9-year-old children in 12 countries. Prevalence of overweight, obesity, stunting, thinness and underweight as well as mean Z-scores of anthropometric indices of height, weight and body mass index were calculated. RESULTS: A total of 168 832 children were included in the analyses and a school participation rate of more than 95% was obtained in 8 out of 12 countries. Stunting, underweight and thinness were rarely prevalent. However, 19.3-49.0% of boys and 18.4-42.5% of girls were overweight (including obesity and based on the 2007 WHO growth reference).The prevalence of obesity ranged from 6.0 to 26.6% among boys and from 4.6 to 17.3% among girls. Multi-country comparisons suggest the presence of a north-south gradient with the highest level of overweight found in southern European countries. CONCLUSIONS: Overweight among 6-9-year-old children is a serious public health concern and its variation across the European Region highly depends on the country. Comparable monitoring of child growth is possible across Europe and should be emphasized in national policies and implemented as part of action plans.

Prevalence of obesity among Portuguese children (6-8 years old) using three definition criteria: COSI Portugal, 2008.

INTRODUCTION: Previous studies place Portugal among the five countries with the highest prevalence of childhood obesity in Europe. This paper describes the prevalence of thinness, overweight and obesity in Portuguese children of 6-8 years of age, based on the first data collection from Childhood Obesity Surveillance Initiative Portugal, which took place during the 2007/2008 school year. METHODS: This study uses a semi-longitudinal design with repeated cross-sectional national representative samples. Specific prevalence of overweight (including obesity) and obesity was determined using three different diagnostic criteria. Across the seven geographic regions, 3765 children were enrolled from 181 schools; 50.3% of participants were males. RESULTS: Using the International Obesity Task Force reference, the prevalence of thinness, overweight and obesity were 4.8%, 28.1% and 8.9%, respectively; using the Center for Disease Control and Prevention reference they were 2.1%, 32.2% and 14.6%, respectively; and according to the World Health Organization reference, they were 1.0%, 37.9% and 15.3%, respectively. Univariate analysis showed a higher risk of obesity in older children, in boys and in the Azores region. The islands of Madeira and the Azores were the regions with the highest prevalence of overweight at 39.4% and 46.6%, respectively, and Algarve was the one with the lowest (21.4%). CONCLUSION: These findings demonstrate the need for urgent action in Portugal and provide policy-makers with comprehensive and detailed information to assist with this.

Overweight and obesity in infants and pre-school children in the European Union: a review of existing data.

The objective of this study was to synthesize available information on prevalence and time trends of overweight and obesity in pre-school children in the European Union. Retrieval and analysis or re-analysis of existing data were carried out. Data sources include WHO databases, Medline and Google, contact with authors of published and unpublished documents. Data were analysed using the International Obesity Task Force reference and cut-offs, and the WHO standard. Data were available from 18/27 countries. Comparisons were problematic because of different definitions and methods of data collection and analysis. The reported prevalence of overweight plus obesity at 4 years ranges from 11.8% in Romania (2004) to 32.3% in Spain (1998-2000). Countries in the Mediterranean region and the British islands report higher rates than those in middle, northern and eastern Europe. Rates are generally higher in girls than in boys. With the possible exception of England, there was no obvious trend towards increasing prevalence in the past 20-30 years in the five countries with data. The use of the WHO standard with cut-offs at 1, 2 and 3 standard deviations yields lower rates and removes gender differences. Data on overweight and obesity in pre-school children are scarce; their interpretation is difficult. Standard methods of surveillance, and research and policies on prevention and treatment, are urgently needed.

Root development under metal stress in Arabidopsis thaliana requires the H+/cation antiporter CAX4.

* The Arabidopsis vacuolar CAtion eXchangers (CAXs) play a key role in mediating cation influx into the vacuole. In Arabidopsis, there are six CAX genes. However, some members are yet to be characterized fully. * In this study, we show that CAX4 is expressed in the root apex and lateral root primordia, and that expression is increased when Ni(2+) or Mn(2+) levels are elevated or Ca(2+) is depleted. * Transgenic plants expressing increased levels of CAX4 display symptoms consistent with increased sequestration of Ca(2+) and Cd(2+) into the vacuole. When CAX4 is highly expressed in an Arabidopsis cax1 mutant line with weak vacuolar Ca(2+)/H(+) antiport activity, a 29% increase in Ca(2+)/H(+) antiport is measured. A cax4 loss-of-function mutant and CAX4 RNA interference lines display altered root growth in response to Cd(2+), Mn(2+) and auxin. The DR5::GUS auxin reporter detected reduces auxin responses in the cax4 lines. * These results indicate that CAX4 is a cation/H(+) antiporter that plays an important function in root growth under heavy metal stress conditions.

Effects of long-term growth hormone therapy on adrenal steroidogenesis in Turner syndrome.

It has been shown that growth hormone (GH) and insulin-like growth factor-1 (IGF1) enhance steroidogenesis responsiveness to ACTH in cultured adrenal cells. To investigate the GH effect on adrenal steroidogenesis in non-GH-deficient subjects, we studied 9 girls with Turner syndrome (chronological age 5.5-7.2 years; bone age 5-7 years). In all subjects an ACTH test (Synacthen depot, 0.25 mg i.v. with blood samples at 0 and 60 min) was performed basally at 8-9 a.m. and 6 months after GH therapy (1 IU/kg/week). 17-Hydroxypregnenolone (17PGN), 17-hydroxyprogesterone (17OHP), dehydroepiandrosterone (DHA), its sulfate (DHA-S), androstenedione and cortisol were evaluated by radioimmunoassay. Two groups of normal girls were selected as controls: group A age-matched the patients at the start of the study, and group B age-matched the patients at the end of the study. The responsiveness of each hormone to ACTH was expressed as the difference between stimulated and basal values. A p value of < 0.01 was considered to indicate significance. There were no significant differences between pre- and posttreatment basal values of 17PGN, 17OHP, DHA, androstenedione and cortisol in the Turner syndrome patients, whereas a significant increase was observed for basal DHA-S (1.57+/-0.31; 1.89+/-0.43 micromol/l, p < 0.01). Comparison of increments before and after GH treatment showed a significant increase in responsiveness to ACTH after GH therapy DHA (p < 0.01). The increase in 17PGN was evident (p < 0.02), but the established significant p value was not reached. No differences for 17OHP, androstenedione and cortisol were found. The stimulated 17PGN/17OHP ratio was significantly higher (p < 0.01) after GH, whereas the 17OHP/androstenedione ratio was considerably lower, but the p value was < 0.02. No differences between pretreatment values with the control group androstenedione was found, whereas basal and stimulated posttreatment values of DHA and stimulated values of 17PGN were higher in patients after GH therapy than in control group B. No differences between the 2 control groups were found. In conclusion our study showed that adrenal steroid responsiveness to ACTH increases in Turner syndrome after long-term treatment with high GH doses. An increase in the number of ACTH adrenal receptors and/or a modulation of enzyme activities may be suggested. The positive or negative pharmacological implications of these data remain to be determined especially when taking into consideration the wide use of GH therapy in non-GH-deficient subjects.

Adult height in short normal adolescent girls treated with gonadotropin-releasing hormone analog and growth hormone.

GnRH analog associated with GH therapy has potential importance for treatment of short stature in subjects without GH deficiency and with a normal onset of puberty. We treated 10 girls with familial short stature with the GnRH analog leuprolide (3.75 mg, im, every 25 days) and GH (0.1 IU/kg.day, sc, 6 days/week). The combined therapies were started simultaneously, and the patients were treated for 28.1 +/- 5.4 (range, 24-36) months. At the onset of treatment, chronological age was 11.6 +/- 1.4 yr, bone age was 10.6 +/- 0.9 yr, height was -2.7 +/- 0.7 SD, predicted height (PH; Bayley-Pinneau score) was 143.2 +/- 3 cm. Target height was 147.6 +/- 5.6 cm. Tanner stage was II-III for breast and genitalia. During treatment, puberty was completely suppressed in all patients. Statistical analysis was performed using Student's t test for paired data. After 12 months of treatment, we observed a significant (P < 0.02) improvement of predicted height (146.2 +/- 3.4 cm). This improvement remained significant (147.6 +/- 3.5; P < 0.001) when treatment was withdrawn. At that time, chronological age was 13.9 +/- 1.2 yr, and bone age was 12.4 +/- 0.7 yr. At the present time (3 +/- 0.97 yr after discontinuation), all of the girls have reached a final height of 144.6 +/- 3 cm (range, 140-149.3 cm). The final height is not significantly different compared with the PH at the beginning of treatment or with target height. These data show that in our patients, combined treatment with GnRH analog and GH, despite a significant improvement in PH during therapy and upon its withdrawal, does not result in a significant increase in adult stature. Larger and perhaps more prolonged studies in patients of both sexes are required to reach definitive conclusions. Nevertheless, the cost of this treatment in terms of both subject compliance and economic cost should be weighed against the small height gain, if any, that may be achieved.