Parental and familial factors influencing physical activity levels in early adolescence: a prospective study

Parental/familial factors are important determinants of the physical activity level (PAL) in children and adolescents, but studies rarely prospectively evaluate their relationships. This study aimed to evaluate the changes in physical activity levels among adolescents from Bosnia and Herzegovina over a two-year period and to determine parental/familial predictors of PAL in early adolescence. A total of 651 participants (50.3% females) were tested at baseline (beginning of high school education; 14 years old on average) and at follow-up (approximately 20 months later). The predictors included sociodemographic characteristics (age, gender) and parental/familial factors (socioeconomic status of the family, maternal and paternal education, conflict with parents, parental absence from home, parental questioning, and parental monitoring). Physical activity levels were evidenced by the Physical Activity Questionnaire for Adolescents (PAQ-A; criterion). Boys were more active than girls, both at baseline (t-test = 3.09, p < 0.001) and at follow-up (t-test = 3.4, p < 0.001). Physical activity level decreased over the observed two-year period (t-test = 16.89, p < 0.001), especially in boys, which is probably a consequence of drop-out from the sport in this period. Logistic regression evidenced parental education as a positive predictor of physical activity level at baseline (OR [95% CI]; 1.38 [1.15–170], 1.35 [1.10–1.65]), and at follow-up (1.35 [1.11–1.69], 1.29 [1.09–1.59], for maternal and paternal education, respectively). Parents with a higher level of education are probably more informed about the importance of physical activity on health status, and thus transfer this information to their children as well. The age from 14 to 16 years is likely a critical period for maintaining physical activity levels in boys, while further studies of a younger age are necessary to evaluate the dynamics of changes in physical activity levels for girls. For maintaining physical activity levels in adolescence, special attention should be paid to children whose parents are less educated, and to inform them of the benefits of an appropriate physical activity level and its necessity for maintaining proper health and growth

Increased tumour dihydroceramide production after Photofrin-PDT alone and improved tumour response after the combination with the ceramide analogue LCL29. Evidence from mouse squamous cell carcinomas

Photodynamic therapy (PDT) has been proven effective for treatment of several types of cancer. Photodynamic therapy alone, however, attains limited cures with some tumours and there is need for its improved efficacy in such cases. Sphingolipid (SL) analogues can promote tumour response in combination with anticancer drugs. In this study, we used mouse SCCVII squamous cell carcinoma tumours to determine the impact of Photofrin-PDT on the in vivo SL profile and the effect of LCL29, a C6-pyridinium ceramide, on PDT tumour response. Following PDT, the levels of dihydroceramides (DHceramides), in particular C20-DHceramide, were elevated in tumours. Similarly, increases in DHceramides, in addition to C20:1-ceramide, were found in PDT-treated SCCVII cells. These findings indicate the importance of the de novo ceramide pathway in Photofrin-PDT response not only in cells but also in vivo. Notably, co-exposure of SCCVII tumours to Photofrin-PDT and LCL29 led to enhanced tumour response compared with PDT alone. Thus, we show for the first time that Photofrin-PDT has a distinct signature effect on the SL profile in vitro and in vivo, and that the combined treatment advances PDT therapeutic gain, implying translational significance of the combination

A genome-wide DNA methylation signature for SETD1B-related syndrome

SETD1B is a component of a histone methyltransferase complex that specifically methylates Lys-4 of histone H3 (H3K4) and is responsible for the epigenetic control of chromatin structure and gene expression. De novo microdeletions encompassing this gene as well as de novo missense mutations were previously linked to syndromic intellectual disability (ID). Here, we identify a specific hypermethylation signature associated with loss of function mutations in the SETD1B gene which may be used as an epigenetic marker supporting the diagnosis of syndromic SETD1B-related diseases. We demonstrate the clinical utility of this unique epi-signature by reclassifying previously identified SETD1B VUS (variant of uncertain significance) in two patients

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

X-linked inhibitor of apoptosis positive nuclear labeling: a new independent prognostic biomarker of breast invasive ductal carcinoma

<p>Abstract</p> <p>Background</p> <p>It's well recognized that X-linked inhibitor of apoptosis (XIAP) was the most potent caspase inhibitor and second mitochondria-derived activator of caspase (Smac) was the antagonist of XIAP. Experiments in vitro identified that down regulation of XIAP expression or applying Smac mimics could sensitize breast cancer cells to chemotherapeutics and promote apoptosis. However, expression status and biologic or prognostic significance of XIAP/Smac in breast invasive ductal carcinoma (IDC) were not clear. The present study aimed to investigate relationship among expression status of XIAP/Smac, apoptosis index (AI), clinicopathologic parameters and prognosis in IDC.</p> <p>Methods</p> <p>Immunohistochemistry and TUNEL experiment were performed to detect expression of XIAP, Smac, ER, PR, HER2 and AI in 102 cases of paraffin-embedded IDC samples respectively. Expression of XIAP/Smac were also detected in limited 8 cases of fresh IDC specimens with Western blot.</p> <p>Results</p> <p>Positive ratio and immunoscore of XIAP was markedly higher than Smac in IDC (<it>P </it>< 0.0001). It was noteworthy that 44 cases of IDC were positive in nuclear for XIAP, but none was for Smac. Expression status of Smac was more prevalent in HER2 positive group than negative group (<it>P </it>< 0.0001) and AI was positively correlated with HER2 protein expression (r_s= 0.265, <it>P </it>= 0.017). The present study first revealed that XIAP positive nuclear labeling (XIAP-N), but not cytoplasmic staining (XIAP-C), was the apoptotic marker correlated significantly with patients' shortened overall survival (<it>P </it>= 0.039). Survival analysis demonstrated that XIAP-N was a new independent prognostic factor except for patient age and lymph node status.</p> <p>Conclusion</p> <p>Disturbed balance of expression between XIAP and Smac probably contributed to carcinogenesis and XIAP positive nuclear labeling was a new independent prognostic biomarker of breast IDC.</p

Synergistic Anti-Tumor Effects of Combination of Photodynamic Therapy and Arsenic Compound in Cervical Cancer Cells: In Vivo and In Vitro Studies

The effects of As4O6 as adjuvant on photodynamic therapy (PDT) were studied. As4O6 is considered to have anticancer activity via several biological actions, such as free radical production and inhibition of VEGF expression. PDT or As4O6 significantly inhibited TC-1 cell proliferation in a dose-dependent manner (P<0.05) by MTT assay. The anti-proliferative effect of the combination treatment was significantly higher than in TC-1 cells treated with either photodynamic therapy or As4O6 alone (62.4 and 52.5% decrease compared to vehicle-only treated TC-1 cells, respectively, P<0.05). In addition, cell proliferation in combination of photodynamic therapy and As4O6 treatment significantly decreased by 77.4% (P<0.05). Cell survival pathway (Naip1, Tert and Aip1) and p53-dependent pathway (Bax, p21Cip1, Fas, Gadd45, IGFBP-3 and Mdm-2) were markedly increased by combination treatment of photodynamic therapy and As4O6. In addition, the immune response in the NEAT pathway (Ly-12, CD178 and IL-2) was also modulated after combination treatment, suggesting improved antitumor effects by controlling unwanted growth-stimulatory pathways. The combination effect apparently reflected concordance with in vitro data, in restricting tumor growth in vivo and in relation to some common signaling pathways to those observed in vitro. These findings suggest the benefit of combinatory treatment with photodynamic therapy and As4O6 for inhibition of cervical cancer cell growth

Targeting of T/Tn Antigens with a Plant Lectin to Kill Human Leukemia Cells by Photochemotherapy

Photochemotherapy is used both for solid tumors and in extracorporeal treatment of various hematologic disorders. Nevertheless, its development in oncology remains limited, because of the low selectivity of photosensitizers (PS) towards human tumor cells. To enhance PS efficiency, we recently covalently linked a porphyrin (TrMPyP) to a plant lectin (Morniga G), known to recognize with high affinity tumor-associated T and Tn antigens. The conjugation allowed a quick uptake of PS by Tn-positive Jurkat leukemia cells and efficient PS-induced phototoxicity. The present study was performed: (i) to evaluate the targeting potential of the conjugate towards tumor and normal cells and its phototoxicity on various leukemia cells, (ii) to investigate the mechanism of conjugate-mediated cell death. The conjugate: (i) strongly increased (×1000) the PS phototoxicity towards leukemic Jurkat T cells through an O-glycan-dependent process; (ii) specifically purged tumor cells from a 1∶1 mixture of Jurkat leukemia (Tn-positive) and healthy (Tn-negative) lymphocytes, preserving the activation potential of healthy lymphocytes; (iii) was effective against various leukemic cell lines with distinct phenotypes, as well as fresh human primary acute and chronic lymphoid leukemia cells; (iv) induced mostly a caspase-independent cell death, which might be an advantage as tumor cells often resist caspase-dependent cell death. Altogether, the present observations suggest that conjugation with plant lectins can allow targeting of photosensitizers towards aberrant glycosylation of tumor cells, e.g. to purge leukemia cells from blood and to preserve the normal leukocytes in extracorporeal photochemotherapy