IGFBP-3 inhibits Wnt signaling in metastatic melanoma cells.

In previous works, we have shown that insulin-like growth factor-binding protein-3 (IGFBP-3), a tissue and circulating protein able to bind to IGFs, decreases drastically in the blood serum of patients with diffuse metastatic melanoma. In agreement with the clinical data, recombinant IGFBP-3 was found to inhibit the motility and invasiveness of cultured metastatic melanoma cells and to prevent growth of grafted melanomas in mice. The present work was aimed at identifying the signal transduction pathways underlying the anti-tumoral effects of IGFBP-3. We show that the anti-tumoral effect of IGFBP-3 is due to inhibition of the Wnt pathway and depends upon the presence of CD44, a receptor protein known to modulate Wnt signaling. Once it has entered the cell, IGFBP-3 binds the Wnt signalosome interacting specifically with its component GSK-3β. As a consequence, the β-catenin destruction complex dissociates from the LRP6 Wnt receptor and GSK-3β is activated through dephosphorylation, becoming free to target cytoplasmic β-catenin which is degraded by the proteasomal pathway. Altogether, the results suggest that IGFBP-3 is a novel and effective inhibitor of Wnt signaling. As IGFBP-3 is a physiological protein which has no detectable toxic effects either on cultured cells or live mice, it might qualify as an interesting new therapeutic agent in melanoma, and potentially many other cancers with a hyperactive Wnt signaling

Polymerization shrinkage and spherical glass mega fillers: Effects on cuspal deflection

Purpose. The Authors analyzed the effect of spherical glass mega fillers (SGMF) on reducing contraction stress in dental composite resins, by means of a cavity model simulating the cuspal deflection which occurs on filled tooth cavity walls in clinical condition. Materials and methods. 20 stylized MOD cavities (C-factor = 0.83) were performed in acrylic resin. The inner surface of each cavity was sand blasted and adhesively treated in order to ensure a valid bond with the composite resin. Three different diameter of SGMF were used (i.e. 1, 1,5, 2 mm). The samples were divided in 4 groups of 5 each: Group 1 samples filled with the composite only; Group 2 samples filled with composite added with SGMFs, Ø1mm (16 spheres for each sample); Group 3 samples filled with composite added with SGMFs, Ø1,5 mm (5 spheres for each sample); Group 4 samples filled with composite added with SGMFs, Ø2 mm (2 spheres for each sample). Digital pictures were taken, in standardized settings, before and immediately after the polymerization of the composite material, placed into the cavities. With a digital image analysis software the distances from the coronal reference points of the cavity walls were measured. Then the difference between the first and second measurement was calculated. The data were analyzed by means of the ANOVA test. Results. A significative reduction on cavity walls deflection, when the composite resin is used in addiction with the SGMFs was observed. The SGMFs of smallest diameter (1mm) showed the better outcome. Conclusion. The SGMFs are reliable in reducing contraction stress in dental composite resins

The Impact of the California Drought on Food Security among Rural Families of Mexican Origin

Introduction: The year 2015 marks the fourth year of a drought in California. With no signs of the drought improving, communities in California are left to prioritize their water usage. In the Central Valley, the limited water supply has forced farmers to prioritize on acreage and planting, decisions that trickle down and may impact farmworker families. Objective: The purpose of this study was to explore the impact of a drought in California on family decision-making and coping strategies in the context of broader community changes affecting rural families of Mexican-origin. Methods: This study recruited participants from the Niños Sanos, Familia Sana (NSFS, Healthy Children, Healthy Family) childhood obesity intervention study, conducted from 2011-2015. The primary occupation of two-thirds of the NSFS families was agricultural work. Based on the US Department of Agriculture 18-item food security assessment tool, a baseline household survey among 336 families in 2012 revealed that 45% of the households were food insecure. In 2015, a bilingual graduate student moderated four focus groups in a convenience sample of 26 NSFS families, who were recruited by promotoras (local lay workers). Males and females were assigned to different focus group discussions, each of which lasted 1 ½ hours. Two researchers reviewed transcriptions of the audio recordings and analyzed them for emerging themes. Results/Conclusions: In this Mexican-origin rural population, households headed by less educated mothers, older fathers, and adults engaged in farm work were most vulnerable to food insecurity. The focus groups revealed community changes including out-migration of families, increased food prices, and changes in employment (fewer hours, less predictable, need to travel further to find work). These changes have led families to shift their family decision-making and economize to cope with the unpredictable nature of the agricultural workforce. Paying bills and rent takes priority over food, clothing, medicine and other expenses. All groups mentioned having to deny child requests and family outings. Women noted increased stress on the family and concern about keeping families together. Men expressed the desire to avoid disruption to their children’s lives but were actively considering moving elsewhere. As a community, they have remained united and working together to withstand the challenges the drought has introduced

Operationalisation of intrinsic capacity in older people and its association with subsequent disability, hospital admission and mortality: results from ELSA

Background Intrinsic capacity (IC) is a new concept in the healthy aging field and has many operationalized definitions. In this study, we operationalized IC using item response theory in the English Longitudinal Study of Ageing (ELSA) and tested the predictive value of the scale using a subsequent functional ability, mortality, and hospital admission. Methods IC was measured at baseline (2004, Wave 2) using 14 dichotomous indicators: word recall, orientation in time, balance, chair rises, walking speed, upper mobility, lower mobility, eyesight, hearing, grip strength, body mass index, waist circumference, depressive symptoms, and life satisfaction. A 2-parameter item response theory model was used to generate a scale of IC at baseline. Logistic regression was used for the prediction of subsequent difficulties, measured by difficulties with ≥1 activities of daily living (ADLs) and ≥1 instrumental activities of daily living (IADLs) at 4 and 8 years after baseline. Competing risk and Cox regressions were employed to test the prediction of hospital admission and mortality, respectively, over a 14-year follow-up. Results IC scores were generated for 4 545 individuals aged on average 70.8 years (standard deviation [SD] 7.93). Better baseline IC scores were associated with reduced risk of subsequent difficulties with ADLs and IADLs, hospital admission (subdistribution hazard ratios [SHR] = 0.99, 95% confidence interval [CI] 0.98–0.99), and mortality (hazard ratios [HR] = 0.98, 95% CI 0.98–0.99), when adjusted for sociodemographic and health-related covariates. Conclusion These results suggest the utility of this IC score as a measure of risk for future adverse outcomes in older people, potentially above that indicated by other sociodemographic and health-related factors

Perception of upper lip augmentation utilizing simulated photography

Background No head to head comparison is available between surgical lip lifting and upper lip filler injections to decide which technique yields the best results in patients. Despite the growing popularity of upper lip augmentation, its effect on societal perceptions of attractiveness, successfulness and overall health in woman is unknown. Methods Blinded casual observers viewed three versions of independent images of 15 unique patient lower faces for a total of 45 images. Observers rated the attractiveness, perceived success, and perceived overall health for each patient image. Facial perception questions were answered on a visual analog scale from 0 to 100, where higher scores corresponded to more positive responses. Results Two hundred and seventeen random observers with an average age of 47 years (standard deviation, 15.9) rated the images. The majority of observers were females (n=183, 84%) of white race (n=174, 80%) and had at least some college education (n=202, 93%). The marginal mean score for perceived attractiveness from the natural condition was 1.5 points (95% confidence interval [CI], 0.9–2.18) higher than perceived attractiveness from the simulated upper lip filler injection condition, and 2.6 points higher (95% CI, 1.95–3.24) than the simulated upper lip lift condition. There was a moderate to strong correlation between the scores of the same observer. Conclusions Simulated upper lip augmentation is amenable to social perception analysis. Scores of the same observer for attractiveness, successfulness, and overall health are strongly correlated. Overall, the natural condition had the highest scores in all categories, followed by simulated upper lip filler, and lastly simulated upper lip lift

Pharmacokinetics and Dosing of Levofloxacin in Children Treated for Active or Latent Multidrug-resistant Tuberculosis, Federated States of Micronesia and Republic of the Marshall Islands

In the Federated States of Micronesia (FSM) and then the Republic of the Marshall Islands (RMI), levofloxacin pharmacokinetics (PK) were studied in children receiving directly observed once-daily regimens (10 mg/kg, age >5 years; 15–20 mg/kg, age ≤5 years) for either multidrug-resistant tuberculosis (MDR TB) disease or latent infection after MDR TB exposure, to inform future dosing strategies

Tuning the Activity and Selectivity of Phenylacetylene Hydrosilylation with Triethylsilane in the Liquid Phase over Size Controlled Pt Nanoparticles

Pt nanoparticles with controlled sizes between 1.6–7.0 nm were anchored onto the surface and pores of SBA-15 silica support. The catalysts were characterized by TEM-ED, BET, XRD, and ICP-MS techniques and were tested in liquid phase hydrosilylation of phenylacetylene with triethylsilane. The activity of the 7.0 nm Pt nanoparticles anchored onto the surface of SBA-15 in hydrosilylation (TOF = 0.107 molecules·site−1·s−1) was ~2 times higher compared to the 5.0 nm Pt/SBA-15 (TOF = 0.049 molecules·site−1·s−1) catalyst and ~10 times higher compared to the 1.6 nm Pt/SBA-15 (TOF = 0.017 molecules·site−1·s−1) catalyst. Regarding the selectivity, bigger nanoparticles produced more vinylsilane-type products (α- and β-(E)-products) and less side products (mainly ditriethylsilane, triethyl(1-phenylethyl)silane and triethyl(phenethyl)silane derived likely from the reduction of the vinylsilane products). However, the selectivity towards the β-(E)-triethyl(styryl)silane was higher in the case of 1.6 nm Pt/SBA-15 catalyst compared to 5.0 nm Pt/SBA-15 and 7.0 nm Pt/SBA-15, respectively, which can be attributed to the beneficial effect of the size differences of the Pt nanoparticles as well as the differences of the quality and quantity of Pt/SiO2 interfaces