The EnergyKids Pilot Study: Comparing Energy Balance of Primary School Children during School and Summer Camp

Children’s energy requirements may vary during school and summer camp days. To evaluate energy balance during these two periods, seventy-eight children (45% females, 8–10 years) living in Parma, Italy, were enrolled in this observational study. Participants completed a 3-day food diary and wore an activity tracker for three consecutive days during a school- and a summer camp-week to estimate energy intake (EI) and energy expenditure (TEE). Height and body weight were measured at the beginning of each period to define children’s weight status. BMI and EI (school: 1692 ± 265 kcal/day; summer camp: 1738 ± 262 kcal/day) were similar during both periods. Both physical activity and TEE (summer camp: 1948 ± 312; school: 1704 ± 263 kcal/day) were higher during summer camp compared to school time. Therefore, energy balance was more negative during summer camp (−209 ± 366 kcal/day) compared to school time (−12 ± 331 kcal/day). Similar results were observed when males and females were analyzed separately but, comparing the sexes, males had a higher TEE and a more negative energy balance than females, during both periods. The results strongly suggest that an accurate evaluation of children’s energy balance, that considers both diet and physical activity, is needed when planning adequate diets for different situations

Folic acid-layered double hydroxides hybrids in skin formulations: Technological, photochemical and in vitro cytotoxicity on human keratinocytes and fibroblasts

Abstract Folic acid (FA) is a key factor in the physiological processes of cell metabolism; as it is involved in DNA synthesis and repair, it can be used in the treatment of aged and photo-damaged skin. The main drawbacks associated to FA use, particularly for topical applications, are the limited solubility and the sensitivity to UV rays. Hybrids of FA with two kinds of layered double hydroxides (ZnAl-LDH and MgAl-LDH) were prepared and characterized showing suitable particle size, flow properties and UV photoprotection. The introduction of FA-LDHs in the external water phase of O/W emulgels produced an enhancement of their flow properties; moreover, the spectrophotometric analyses showed that very good photostability is maintained even after their introduction into the formulations. In-vitro release studies showed that the FA-LDH containing emulgels promoted a sustained FA release as expected. Finally, the safety of FA-LDH was evaluated by in-vitro studies performed on human keratinocytes (HaCaT) and human primary dermal fibroblasts (as a skin representative). The obtained results showed a high cytotoxic effect of ZnAl-LDH-FA in both cell lines

Nitric oxide donors increase PVR/CD155 DNAM-1 ligand expression in multiple myeloma cells: role of DNA damage response activation

Background: DNAX accessory molecule-1 (DNAM-1) is an activating receptor constitutively expressed by macrophages/ dendritic cells and by T lymphocytes and Natural Killer (NK) cells, having an important role in anticancer responses; in this regard, combination therapies able to enhance the expression of DNAM-1 ligands on tumor cells are of therapeutic interest. In this study, we investigated the effect of different nitric oxide (NO) donors on the expression of the DNAM-1 ligand Poliovirus Receptor/CD155 (PVR/CD155) in multiple myeloma (MM) cells. Methods: Six MM cell lines, SKO-007(J3), U266, OPM-2, RPMI-8226, ARK and LP1 were used to investigate the activity of different nitric oxide donors [DETA-NO and the NO-releasing prodrugs NCX4040 (NO-aspirin) and JS-K] on the expression of PVR/CD155, using Flow Cytometry and Real-Time PCR. Western-blot and specific inhibitors were employed to investigate the role of soluble guanylyl cyclase/cGMP and activation of the DNA damage response (DDR). Results: Our results indicate that increased levels of nitric oxide can upregulate PVR/CD155 cell surface and mRNA expression in MM cells; in addition, exposure to nitric oxide donors renders myeloma cells more efficient to activate NK cell degranulation and enhances their ability to trigger NK cell-mediated cytotoxicity. We found that activation of the soluble guanylyl cyclase and increased cGMP concentrations by nitric oxide is not involved in the up-regulation of ligand expression. On the contrary, treatment of MM cells with nitric oxide donors correlated with the activation of a DNA damage response pathway and inhibition of the ATM /ATR/Chk1/2 kinase activities by specific inhibitors significantly abrogates up-regulation. Conclusions: The present study provides evidence that regulation of the PVR/CD155 DNAM-1 ligand expression by nitric oxide may represent an additional immune-mediated mechanism and supports the anti-myeloma activity of nitric oxide donors

Plasma Small Extracellular Vesicle Cathepsin D Dysregulation in GRN/C9orf72 and Sporadic Frontotemporal Lobar Degeneration

Emerging data suggest the roles of endo-lysosomal dysfunctions in frontotemporal lobar degeneration (FTLD) and in other dementias. Cathepsin D is one of the major lysosomal proteases, mediating the degradation of unfolded protein aggregates. In this retrospective study, we investigated cathepsin D levels in human plasma and in the plasma small extracellular vesicles (sEVs) of 161 subjects (40 sporadic FTLD, 33 intermediate/pathological C9orf72 expansion carriers, 45 heterozygous/homozygous GRN mutation carriers, and 43 controls). Cathepsin D was quantified by ELISA, and nanoparticle tracking analysis data (sEV concentration for the cathepsin D level normalization) were extracted from our previously published dataset or were newly generated. First, we revealed a positive correlation of the cathepsin D levels with the age of the patients and controls. Even if no significant differences were found in the cathepsin D plasma levels, we observed a progressive reduction in plasma cathepsin D moving from the intermediate to C9orf72 pathological expansion carriers. Observing the sEVs nano-compartment, we observed increased cathepsin D sEV cargo (ng/sEV) levels in genetic/sporadic FTLD. The diagnostic performance of this biomarker was fairly high (AUC = 0.85). Moreover, sEV and plasma cathepsin D levels were positively correlated with age at onset. In conclusion, our study further emphasizes the common occurrence of endo-lysosomal dysregulation in GRN/C9orf72 and sporadic FTLD

An Exploratory Study of Field Failures

Field failures, that is, failures caused by faults that escape the testing phase leading to failures in the field, are unavoidable. Improving verification and validation activities before deployment can identify and timely remove many but not all faults, and users may still experience a number of annoying problems while using their software systems. This paper investigates the nature of field failures, to understand to what extent further improving in-house verification and validation activities can reduce the number of failures in the field, and frames the need of new approaches that operate in the field. We report the results of the analysis of the bug reports of five applications belonging to three different ecosystems, propose a taxonomy of field failures, and discuss the reasons why failures belonging to the identified classes cannot be detected at design time but shall be addressed at runtime. We observe that many faults (70%) are intrinsically hard to detect at design-time

Non-neural phenotype of spinal and bulbar muscular atrophy: Results from a large cohort of Italian patients

Objective: To carry out a deep characterisation of the main androgen-responsive tissues involved in spinal and bulbar muscular atrophy (SBMA). Methods: 73 consecutive Italian patients underwent a full clinical protocol including biochemical and hormonal analyses, genitourinary examination, bone metabolism and densitometry, cardiological evaluation and muscle pathology. Results: Creatine kinase levels were slightly to markedly elevated in almost all cases (68 of the 73; 94%). 30 (41%) patients had fasting glucose above the reference limit, and many patients had total cholesterol (40; 54.7%), low-density lipoproteins cholesterol (29; 39.7%) and triglyceride (35; 48%) levels above the recommended values. Although testosterone, luteinising hormone and follicle-stimulating hormone values were generally normal, in one-third of cases we calculated an increased Androgen Sensitivity Index reflecting the presence of androgen resistance in these patients. According to the International Prostate Symptom Score (IPSS), 7/70 (10%) patients reported severe lower urinal tract symptoms (IPSS score >19), and 21/73 (30%) patients were moderately symptomatic (IPSS score from 8 to 19). In addition, 3 patients were carriers of an indwelling bladder catheter. Videourodynamic evaluation indicated that 4 of the 7 patients reporting severe urinary symptoms had an overt prostate-unrelated bladder outlet obstruction. Dual-energy X-ray absorptiometry scan data were consistent with low bone mass in 25/61 (41%) patients. Low bone mass was more frequent at the femoral than at the lumbar level. Skeletal muscle biopsy was carried out in 20 patients and myogenic changes in addition to the neurogenic atrophy were mostly observed. Conclusions: Our study provides evidence of a wide non-neural clinical phenotype in SBMA, suggesting the need for comprehensive multidisciplinary protocols for these patients. \ua9 2016 Published by the BMJ Publishing Group Limited

Impairment of the autophagic flux in astrocytes intoxicated by trimethyltin

Autophagy is generally considered a degradation pathway involved in many neurodegenerative processes. It is induced by different stress conditions such as starvation improving cell survival. Conversely, an excess activation of autophagy can drive cells to death by a sort of self-cannibalism. Toxic compounds such as arsenic and lead have been described to affect autophagy in a different way by blocking the correct execution of this pathway. Our previous results show that in hippocampal neuronal cultures the toxic compound trimethyltin (TMT) determines the formation of autophagic vacuoles and that autophagy inducers (lithum, rapamycin) improves neuronal survival (Fabrizi et al., 2012). The present data show that in astrocytes TMT similarly activates the autophagic pathway. Differently from neurons, in astrocytes autophagy inducers are ineffective in modifying cell survival. Moreover, the analysis of the LC3B conversion show in TMT-treated astrocytes a precocious block of the late stages of autophagy which ultimately leads to p62 accumulation, nrf-2 nuclear translocation and induction of ARE-responsive genes

Dose/dense metronomic chemotherapy with fractioned cisplatin and oral daily etoposide enhances the anti-angiogenic effects of bevacizumab and has strong antitumor activity in advanced non-small-cell-lung cancer patients.

Background: We designed a translational clinical trial to investigate whether a dose/dense chemotherapy regimen is able to enhance in patients with non-small-cell-lung-cancer, the anti-angiogenic, and anti-tumor activity of bevacizumab, a murine/human monoclonal antibody to the vasculo-endothelial-growth-factor (VEGF) Patients and Methods: Forty-eight patients (42 males and 6 females) with stage IIIB/IV non-small-cell-lung-cancer, a mean age of 68 years, and ECOG ≤ 2 were enrolled in the study. They received every three weeks fractioned cisplatinum (30 mg/sqm, days 1-3) and oral etoposide (50 mg, days 1-15) and were divided in 5 cohorts receiving different bevacizumab dosages [0; 2.5; 5; 7.5; and 10 mg/kg] on the day 3. Results: The combined treatment was able of inducing a significant decline in the blood-perfusion of primary tumor (NMR-study); in serum levels of VEGF, angiopoietin-1, thrombospondin-1; and in the number of VEGF-transporting cells. In the group of 40 patients who received bevacizumab ther..