Multi-Determinants Analysis of Molecular Alterations for Predicting Clinical Benefit to EGFR-Targeted Monoclonal Antibodies in Colorectal Cancer

KRAS mutations occur in 35-45% of metastatic colorectal cancers (mCRC) and preclude responsiveness to EGFR-targeted therapy with cetuximab or panitumumab. However, less than 20% patients displaying wild-type KRAS tumors achieve objective response. Alterations in other effectors downstream of the EGFR, such as BRAF, and deregulation of the PIK3CA/PTEN pathway have independently been found to give rise to resistance. We present a comprehensive analysis of KRAS, BRAF, PIK3CA mutations, and PTEN expression in mCRC patients treated with cetuximab or panitumumab, with the aim of clarifying the relative contribution of these molecular alterations to resistance.We retrospectively analyzed objective tumor response, progression-free (PFS) and overall survival (OS) together with the mutational status of KRAS, BRAF, PIK3CA and expression of PTEN in 132 tumors from cetuximab or panitumumab treated mCRC patients. Among the 106 non-responsive patients, 74 (70%) had tumors with at least one molecular alteration in the four markers. The probability of response was 51% (22/43) among patients with no alterations, 4% (2/47) among patients with 1 alteration, and 0% (0/24) for patients with > or =2 alterations (p<0.0001). Accordingly, PFS and OS were increasingly worse for patients with tumors harboring none, 1, or > or =2 molecular alteration(s) (p<0.001).When expression of PTEN and mutations of KRAS, BRAF and PIK3CA are concomitantly ascertained, up to 70% of mCRC patients unlikely to respond to anti-EGFR therapies can be identified. We propose to define as 'quadruple negative', the CRCs lacking alterations in KRAS, BRAF, PTEN and PIK3CA. Comprehensive molecular dissection of the EGFR signaling pathways should be considered to select mCRC patients for cetuximab- or panitumumab-based therapies

Perception of Adequacy on Sports Facilities during Schools\u2019 P.E. and Extra Leisure Activities in a Cohort of 1544 Teens

The aim of this qualitative study is to define the perception of adequacy on sport/s facility/ies (SF) during physical education and school sports (PESS) and extra school physical activities (PA). The study population consisted of 1544 students aged between 11 and 19 years old (F: 49.6%; M: 50.4%; height: 1.7\ub111.9 m; weight: 55.7\ub112.4 kg; BMI: 20.2\ub15.1 kg/m2). The sample was randomized from eighteen secondary schools in northern Italy, and was divided into two groups depending on the level of education attended: 11 to 14 years old, lower grade (LG); and 15 to 19 upper (UG). Both groups were asked to fill a themed multi-area questionnaire inquiring about the amount of time spent in PA on a weekly basis, the types of SF utilized, and a detailed evaluation of the provided services whilst using the same facilities. Almost eight students out of ten (79.1%) performed PA during extra PESS time. Ranking of SF assessed: 30.9% outdoor fields; 25.4% fitness & health gyms; 21.6% sport halls; 11.2% pools; and 10.9% other facilities types. A total of 31.7% of students perceive their own sports structure comprehensively similar compared with the others of the same category in which they usually act, and 4.6% noticeably lower; highly significant is how, this last data, negatively increase by 88% from LG to UG. Based on a 5-points Likert Scale, the overall perception regarding the adequacy on SF is at a more than acceptable level with an average 3.68\ub11.1 about PESS, and a 4.0\ub11.0 for extra leisure PA. Nevertheless, SF could run the real risk of becoming too outdated without good maintenance and focused investments in a short-medium term. Additionally, 41.4% of the sample voted the quality of the SF as \u201cessential\u201d (10.7%), or \u201cimportant\u201d (30.7%) to reach the personal PA aims

PERCEPTION OF ADECUACY ON SPORTS FACILITIES DURING SCHOOLS' P.E. AND EXTRA LEISURE ACTIVITIES IN A COHORT OF 1544 TEENS

Introduction The aim of this qualitative study is to define the perception of adequacy on sport/s facility/ies (SF) during P.E. school classes and extra physical activities (physical activity/ies, PA). Methods The study population consisted of 1544 students aged between 11 and 20 years old (height, 1,7\ub111,9 m; weight, 55,7\ub112,4 kg; BMI, 20,2\ub15,1 kg/m2), and was divided into two groups: 11 to 14 lower grade (LG), 15 to 20 upper (UG). Both groups were asked to fill a multi-area questionnaire inquiring about the amount of time spent in PA on a weekly basis, the types of SF utilized, a detiled evaluation of the provided services whilst using the same facilities. Results Almost eight students out of ten (79,08%) performed PA during extra-school time. Ranking of SF assessed: 30,9% outdoor fields, 25,4% fitness &amp; health gyms, 21,6% sport halls, 11,2% pools and 10,9% others facilities types. Recorded order of the total scores achieved, the worst evaluations provided are referred to: care and hygiene of the global spaces (3,55/5), functionality of locker rooms (3,56/5) and structural state of wear (3,69/5). 31,7% of students perceive their own structure comprehensively similar compared with the others of the same category in which they act and 4,6% noticeably lower; highly significant is how this last data increase by 88% from LG to UG. The 41,4% of the sample voted the quality of the SF as essential (10,7%) or important (30,7%) to reach the personal PA aims, the 41,4% quantify as rather relevant. Conclusion The overall perception regarding the adequacy on SF is at a more than acceptable level with a 3.68/5 as regards school P.E. and a 4.03/5.00 for extra leisure sport activities. Nevertheless SF could run the real risk of becoming too outdated without good maintenance and focused investments

Aggression during PE lessons with Mini-Rugby and Fight

The purpose of this study is to evaluate the effectiveness of a block of ten P.E. lessons on teenagers (n°= 46 experimental group, EG; and n°= 27 control group, CG) when playing mini-rugby and fights. Students completed the Aggression Questionnaire (AQ) before and after this period. The 29 items focused on the four aspects of aggression: physical (PA, 9 items), verbal (VA, 5), anger (A, 7) and hostility (H, 8). For each question, they wrote from 1 (false) to 5 (true). Regarding the Δ% an incremental % of EG on CG was found: 13.37% VA, 7.51% A, 5.15% H and 8.36% TOT AQ; the only value that decreased was PA (-1.76%). The Δ% average, of the four subscales, is positively equal to 10.63% for EG, while CG showed a -0.83%. With regards to the total score, the values obtained are the following: PA (EG) -1.43/PA (CG) +2.11 [average +0.34], VA (EG) -2.37/VA (CG) -0.63 [-1.5], A (EG) -2.06/A (CG) -1.67 [-1.87], H (EG) -0.25/H (CG) +0.37 [+0.06] and TOT AQ (EG) -4.82/TOT AQ (CG) -1.18 [-3]. The test showed that the aggression improved by 10% in EG

RISK FACTORS OF BACK PAIN IN PRIMARY SCHOOL CHILDREN

INTRODUCTION The aim of this study was to determine the impact of back pain in primary school children and identify any predisposing risk factors. We aimed to address two fundamental questions: 1) What percentage of primary school students suffer for back pain? 2) What are the main risk factors of back pain in this population? METHODS A group of 804 children aged from 5 to 11 years was tested. The sampling involved both sexes and was based on random sampling. Data were collected through a survey sent to the pupil’s parents and involved a questionnaire, SDQ-Ita (R. Goodman, 1997) concerning anthropometric data, ability/ difficulties (psychological /psychosocial) and lifestyle. Specific questions on pain and back diseases were asked only to those parents whose children had already encountered this problem. Data are expressed as Average and Standard Deviation, where appropriate. Graph data are expressed as a percentage. Descriptive Statistics was performed with the Microsoft Office Excel 2003 (Professional Edition). Inferential Statistics was performed with the statistical program Statview 5.0. implementing the Binary Logistic Multiple Regression, also calculating the Odds Ratio and Confidence Interval. RESULTS Risk factors considered were: female sex, the index of weekly lack of movement and family history of back pain. The incidence of back pain in the sample analyzed was 18%. The incidence of back problems steadily increased from the Year 1 (7.4%) to Year 5 (27.5%) of primary school. The difference between the sexes was 5.3%, (20.2% in girls versus 14.9% in males). Pathological familiarity with at least one family member presenting back pain, was found in 48% of sample examined. The data show for Years 1, 2 and 3 that, as the average time spent in sedentary activities increases from 24% in Year 1 to 40% in Year 3, reaching up to 50 hours per week in Years 4 and 5, the probability of back pain/disorders increases to 57% and 58%. DISCUSSION In correspondence with the literature, we found that there was no correlation between back pain and sleeping position during the night and between back diseases and psychological/ psychosocial factors identified by the questionnaire SDQ-Ita. Too much activity or the practice of a sport on a regular basis for more than twice a week does not seem to increase risk of back pain. The present findings warrant the implementation of programmes aimed at reducing physical inactivity among school children. The effectiveness of such programmes requires not only the involvement of coaches and educators but also family support. The best prevention of back pain and spine disorders should in fact start at an early ag

RISK FACTORS OF BACK PAIN IN PRIMARY SCHOOL CHILDREN

INTRODUCTION The aim of this study was to determine the impact of back pain in primary school children and identify any predisposing risk factors. We aimed to address two fundamental questions: 1) What percentage of primary school students suffer for back pain? 2) What are the main risk factors of back pain in this population? METHODS A group of 804 children aged from 5 to 11 years was tested. The sampling involved both sexes and was based on random sampling. Data were collected through a survey sent to the pupil’s parents and involved a questionnaire, SDQ-Ita (R. Goodman, 1997) concerning anthropometric data, ability/ difficulties (psychological /psychosocial) and lifestyle. Specific questions on pain and back diseases were asked only to those parents whose children had already encountered this problem. Data are expressed as Average and Standard Deviation, where appropriate. Graph data are expressed as a percentage. Descriptive Statistics was performed with the Microsoft Office Excel 2003 (Professional Edition). Inferential Statistics was performed with the statistical program Statview 5.0. implementing the Binary Logistic Multiple Regression, also calculating the Odds Ratio and Confidence Interval. RESULTS Risk factors considered were: female sex, the index of weekly lack of movement and family history of back pain. The incidence of back pain in the sample analyzed was 18%. The incidence of back problems steadily increased from the Year 1 (7.4%) to Year 5 (27.5%) of primary school. The difference between the sexes was 5.3%, (20.2% in girls versus 14.9% in males). Pathological familiarity with at least one family member presenting back pain, was found in 48% of sample examined. The data show for Years 1, 2 and 3 that, as the average time spent in sedentary activities increases from 24% in Year 1 to 40% in Year 3, reaching up to 50 hours per week in Years 4 and 5, the probability of back pain/disorders increases to 57% and 58%. DISCUSSION In correspondence with the literature, we found that there was no correlation between back pain and sleeping position during the night and between back diseases and psychological/ psychosocial factors identified by the questionnaire SDQ-Ita. Too much activity or the practice of a sport on a regular basis for more than twice a week does not seem to increase risk of back pain. The present findings warrant the implementation of programmes aimed at reducing physical inactivity among school children. The effectiveness of such programmes requires not only the involvement of coaches and educators but also family support. The best prevention of back pain and spine disorders should in fact start at an early age