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Background: Safinamide modulates both dopaminergic and glutamatergic systems with positive effects on motor and non-motor symptoms of Parkinson's disease (PD). The drug utilization study SYNAPSES was designed to investigate the use of safinamide in routine clinical practice, as recommended by the European Medicines Agency. Objective: To describe the occurrence of adverse events in PD patients treated with safinamide in real-life conditions. Methods: The SYNAPSES trial is an observational, European, multicenter, retrospective-prospective cohort study. Patients were followed up to 12 months with analyses performed in the overall population and in patients aged >75 years, with relevant comorbidities and with psychiatric conditions. Results: Of the 1610 patients included, 82.4% were evaluable after 12 months with 25.1% of patients >75 years, 70.8% with relevant comorbidities and 42.4% with psychiatric conditions. During observation 45.8% patients experienced adverse events, 27.7% patients had adverse drug reactions and 9.2% patients had serious adverse events. The adverse events were those already described in the patients' information leaflet. The majority were mild or moderate and completely resolved and no differences were detected between the subgroup of patients. Clinically significant improvements were seen in the UPDRS motor score and in the UPDRS total score in >= 40% of patients, according to the criteria developed by Shulman et al. Conclusion: The SYNAPSES study confirms the good safety profile of safinamide even in special groups of patients. Motor complications and motor scores improved with clinically significant results in the UPDRS scale maintained in the long-term.

Exposure to tobacco smoke is a well-known risk factor for childhood asthma and reduced lung function, but the effect on airway inflammation in preschool-aged children is unclear.To examine the effect of parental smoking on lung function and fractional concentration of exhaled nitric oxide (Feno) in relation to both parental reports and children's urine cotinine concentrations in preschool-aged children with multiple-trigger wheeze.A total of 105 3- to 7-year-old children with multiple-trigger wheeze and lung function abnormalities were recruited. Lung function was assessed by impulse oscillometry, and Feno measurements were performed. Exposure to tobacco smoke was determined by parental reports and measurement of children's urinary cotinine concentrations.Forty-three percent of the children were exposed to environmental tobacco smoke according to parental reports. The Feno level was significantly higher in children with a smoking mother (n = 27) than in children with a nonsmoking mother (23.4 vs 12.5 ppb, P = .006). The Feno level expressed as z score and the cotinine level correlated significantly (P = .03). Respiratory resistance at 5 Hz was higher in children exposed to maternal smoking than in others (0.99 vs 0.88 kPas/L, P = .005). Urinary cotinine concentrations reflected well parental reports on their daily smoking and increased relative to the number of cigarettes smoked in the family (P.01). Atopy was found in 75% of the children, but it was not associated with the Feno value (P = .65).Maternal smoking was associated with increased Feno value and poorer lung function in steroid-naive preschool children with multiple-trigger wheeze. Larger controlled trials are needed to generalize the results.

Background— Exposure to tobacco smoke is associated with markers of preclinical atherosclerosis in adults, but its effect on arterial structure in adolescents is unknown. Methods and Results— Healthy 13-year-old adolescents from the atherosclerosis prevention trial STRIP were studied. Maximum carotid and aortic intima-media thickness and brachial artery flow-mediated dilation were measured in 494 adolescents using high-resolution ultrasound. Serum lipid, lipoprotein, and apolipoprotein (Apo) A-I and B concentrations were determined using standard methods. Exposure to tobacco smoke was measured annually between ages 8 and 13 years using serum cotinine concentrations, analyzed with gas chromatography. To define longitudinal exposure, cotinine values of children having serum cotinine measured 2 to 6 times during follow-up were averaged and divided into tertiles (exposure groups): low (n=160), intermediate (n=171), and high (n=163). Adolescents with higher longitudinal exposure to tobacco smoke had increased carotid intima-media thickness (exposure groups [mean±SD]: low, 0.502±0.079 mm; intermediate, 0.525±0.070 mm; high, 0.535±0.066 mm; P P =0.008). The flow-mediated dilation decreased when cotinine level increased (exposure groups: low, 10.43±4.34%; intermediate, 9.78±4.38%; high, 8.82±4.14%; P =0.004). Moreover, ApoB ( P =0.014) and ApoB/ApoA-I ratio ( P =0.045) increased with increase in cotinine level. The associations between tobacco smoke exposure and ultrasound variables were unchanged after adjusting for traditional atherosclerosis risk factors and for ApoB. Conclusions— Frequent exposure to tobacco smoke is independently associated with arterial changes of preclinical atherosclerosis and increased ApoB levels among healthy adolescents. Clinical Trial Registration— clinicaltrials.gov. Identifier: NCT00223600.

Background— Passive smoking is associated with early arterial damage in adults, but its effect on endothelial function in children is unknown. Methods and Results— Serum cotinine concentration was measured annually in children between 8 and 11 years of age who had participated since infancy in a randomized, prospective atherosclerosis prevention trial (Special Turku Coronary Risk Factor Intervention Project for children [STRIP]). At age 11, endothelium-dependent flow-mediated vasodilatory responses of the brachial artery were examined with high-resolution ultrasound in 402 children. These children were divided into 3 groups according to serum cotinine concentrations: the noncotinine group (nondetectable cotinine, n=229), the low cotinine group (cotinine between 0.2 and 1.6 ng/mL, n=134), and the top decile cotinine group (cotinine ≥1.7 ng/mL, n=39). Longitudinal cotinine data in children aged 8 to 11 years and ultrasound studies were available in 327 children. At age 11, the increase in cotinine concentration was associated with attenuated peak flow-mediated dilation response (mean±SD: the noncotinine group 9.10±3.88%, the low-cotinine group 8.57±3.78%, and the top-decile cotinine group 7.73±3.85%; P =0.03 for trend). Similarly, total dilation response (the area under the dilation response versus time curve between 40 and 180 seconds after hyperemia) was affected by the cotinine level ( P =0.02 for trend). These trends were not explained by traditional atherosclerosis risk factors. Arterial measures and passive smoking showed even stronger associations when longitudinal cotinine data were used (peak flow-mediated dilation, P =0.01 for trend; total dilation response, P =0.008 for trend). Conclusions— Exposure to environmental tobacco smoke confirmed by serum cotinine concentrations impairs endothelial function in a dose-dependent manner in 11-year-old children.

To evaluate changes that occur in serum cholesterol ester fatty acid composition during the transition from typical infant feeding to a more adult type of nutrition, this study compared the effects on serum cholesterol ester fatty acids of breast milk or formula at the age of 7 mo with effects caused by 6-mo dietary intervention in 137 children. The intervention [Special Turku coronary Risk factor Intervention Project for children (STRIP baby project)] aimed at a reduction of saturated fat intake to 10% of energy after the age of 1 y without purposefully influencing total fat intake. Nutrient intakes were calculated from 3-d food records. At the age of 7 mo, i.e. before dietary education began, milk type markedly influenced dietary and serum cholesterol ester fatty acid composition (mean serum cholesterol ester 16:0 in breastfed vs formula-fed infants, 13.7% vs 12.0%, respectively, p < 0.001; serum cholesterol ester 18:2n-6 50.6% vs 57.6%, p < 0.001). At the age of 13 mo the calculated fat intake of the intervention and control children differed markedly but serum cholesterol ester fatty acid compositions in all children resembled closely those measured in 7-mo-old breastfed infants, e.g. at the age of 13 mo the relative proportions of 18:2n-6 were 49.9% and 51.1% in previously formula-fed intervention and control children, respectively, and 50.3% and 50.1% in previously breastfed intervention and control children, respectively. In conclusion, serum cholesterol ester fatty acid composition reflected differences in dietary fat quality (breast milk or formula) at the age of 7 mo, whereas dietary intervention as applied in the STRIP baby project had only a minimal effect. □Cholesterol esters, dietary intervention, fatty acids, infant feeding

STRIP (the Special Turku coronary Risk factor Intervention Project) is an ongoing intervention trial which aims at a permanent reduction in the intake of saturated fat and cholesterol starting in childhood. A total of 75 intervention and 63 control children was studied consecutively at the ages of 7 and 13 mo, and 2, 3 and 5 y to evaluate the influence of such intervention on serum cholesterol ester (CE) fatty acid composition, a widely used biomarker of fatty acid intake. Analysis of 4-d food records showed that total intake of fat and of saturated fat increased with age in both groups of children but was constantly lower in intervention than in control children, e.g. at the age of 5 y the mean intakes of total fat and of saturated fatty acids were 31.1 E% and 33.9 E% and 12.1 E% and 14.6E% in intervention and control children, respectively (p = 0.009 and 0.0001, respectively). Serum CE fatty acid compositions did not differ between the 2 groups at any age; the mean proportion of CE linoleic acid was 52.4% and 52.0% in 5-y-old intervention and control children, respectively. Correlation analysis showed, however, that the percentage of linoleic acid and of polyunsaturated fatty acids in CE reflected well the respective dietary intakes (r= 0.36; p = 0.0001 for both coefficients). In conclusion, CE fatty acid composition did not differ between the intervention and control groups, whereas CE linoleic and total polyunsaturated fatty acids reflected well the differences in their intakes at the individual level.

OBJECTIVE. The goal was to assess the relationship between passive smoking and arterial elasticity in children. METHODS. Healthy 11-year-old children (N = 386) from an atherosclerosis prevention trial (Special Turku Coronary Risk Factor Intervention Project for Children) were studied. Aortic and carotid elasticities were determined by using M-mode ultrasound imaging based on measurements of blood pressure and arterial diameter changes during the cardiac cycle. The aortic stiffness index, Young's elastic modulus, and distensibility and the respective indices for the carotid artery were calculated. Exposure to tobacco smoke was measured by using serum cotinine concentrations, and children were classified into 3 groups, that is, the noncotinine group (n = 220; undetectable cotinine levels), the low-cotinine group (n = 127; cotinine levels of 0.2–1.6 ng/mL), and the top-decile cotinine group (n = 39; cotinine levels of ≥1.7 ng/mL). RESULTS. Higher cotinine concentrations were associated with increased aortic stiffness index values. An increase in aortic Young's elastic modulus and a decrease in aortic distensibility were observed across the cotinine groups. In multivariate regression models, the cotinine level remained a significant explanatory variable regarding all aortic elasticity indices. Carotid elasticity indices showed no differences across the cotinine groups. CONCLUSIONS. Childhood exposure to tobacco smoke (verified with serum cotinine levels) decreases aortic elastic properties in healthy children.

Este trabalho trata do efeito da hibridização do reforço, através da adição de uma carga mineral (bentonita) nanoparticulada, no desempenho mecânico de compósitos poliuretano/sisal contendo 25% em massa de fibras de sisal e moldados por compressão. As propriedades mecânicas, de tração e impacto, dos sistemas compósitos estudados foram avaliadas em função do teor (0-10% em massa) e de modificações químicas da carga mineral. Os efeitos do envelhecimento térmico nas propriedades tênseis (sigma, E, épsilon) de compósitos selecionados também foram investigados. O reforço mineral (Bentonita sódica Brasgel-PA) foi empregado em quatro formas, a saber: a) como fornecido (sem tratamento), b) tratado com ácido clorídrico (0,6N), c) modificado com cloreto de dodecil dimetil benzil amônio (Dodigen) e d) modificado com brometo de cetil trimetil amônio (Cetremide). Os resultados indicam que a incorporação da bentonita eleva as propriedades mecânicas dos compósitos e que melhores propriedades foram obtidas quando a bentonita foi tratada com o ácido clorídrico. O envelhecimento térmico em tempos curtos (até 4 dias) provocou elevação no módulo elástico e resistência na ruptura dos compósitos, o que foi atribuído à pós-cura da matriz. Em tempos longos (32 dias) a exposição térmica causou decréscimo nas propriedades tênseis (sigma, E, épsilon) dos compósitos investigados, o que foi atribuído à degradação oxidativa da matriz e dos reforços. O compósito mais resistente ao envelhecimento térmico foi o híbrido cuja carga mineral foi organofilizada com o sal Cetremide. Anáslies por DRX e MEV indicam que a estrutura dos compósitos híbridos é um misto de micro e nanocompósito. This work deals with filler hybridization effects, by the addition of a nanoparticulate mineral filler (bentonite), on the mechanical performance of compression molded Polyurethane/sisal composites with 25 wt % fiber content. Composite tensile and impact properties were evaluated as a function of mineral filler content (0-10 wt %) and chemical modifications. Thermal aging effects onf tensile (sigma, E, epsilon) properties of selected composites were also ascertained. The mineral filler (Brasgel PA sodium bentonite) was employed in the following forms: a) as received; b) treated with a 0,6N HCl solution; c) chemically modified with dodecyl dimethyl benzyl ammonium chloride (Dodigen) and d) chemically modified with cetyl trimethyl ammonium bromide (Cetremide). Our results show that bentonite addition increases the mechanical properties of PU/sisal composites and that best overall mechanical performances was achieved with addition of the hydrochloric acid trated mineral filler. Thermal aging for short times (up to 4 days) led to small increases in composite's elastic modulus na tensile strengths, which was attributed to post-curing of the matrix. Long thermal exposure (32 days) led to decreases in composite tensile properties (sigma, E, epsilon), which was attributed to oxidative degradation of both: matrix and sisal fibers. The most thermally resistant composite was the hybrid (PU/sisal-bentonite) whose mineral filler was chemically modified with Cetremide. DRX and SEM data indicate the hybrids with organofilized bentonites to be composed of micro and nanocomposite structures.

Objectives: The major RNase activity of leukocytes has been attributed to eosinophil-derived neurotoxin EDN. Depletion of eosinophils enables RT-PCR from 10 5 leukocytes without RNA extraction. In this study we introduced streptavidin-coated PCR tube strips for the selection of eosinophil-free leukocytes for RT-PCR analysis. Design and methods: Polypropylene 0.2 ml PCR tube strips were coated with streptavidin and biotinylated antibodies against cell surface antigens were attached to the tubes. CD7-positive T-lymphocytes, CD19-positive B-lymphocytes and CD16-positive cells (mainly neutrophils and monocytes) were positively selected by incubating of 1-2 × 10 5 leukocytes in the antibody-coated PCR tubes for 30 min at 23°C. Results: The mean amount of cells bound into a tube was 31,500 (CV25%) T-cells and 8,600 (CV61%) B-cells from 12 blood samples, and 23,600 (CV22%) CD16+ cells from 17 samples. The influence of selected cell lysate on the RT-PCR analysis of Philadelphia chromosome ( bcr/abl translocation) from 100 K562 cells was small: 78% (CV28%) of the leukocyte-free signal was obtained in the presence of CD16+ cells or 89% (CV15%) and 99% (CV11%) and in the presence of T-cells and B-cells, respectively. Conclusions: These results suggest that through the introduction of eosinophil-free cell population into RT-PCR a reproducible method with reasonable leukocyte yield and avoiding RNA extraction was developed.

To evaluate the effect of dietary low-saturated fat, low-cholesterol intervention on fat intake and fatty acid compositions in serum cholesterol ester (CE), phospholipid (PL) and triglyceride (TG) fractions in five-year-old children.The STRIP project is a prospective, randomised intervention project in which 1062 seven-month-old infants were recruited from the well-baby clinics. 764 children participated in the 5-year follow-up; 202 of them were randomly selected for this study. Diet was assessed with 4-d dietary records. Serum CE, PL and TG fatty acid compositions were analysed with gas-liquid chromatography.Saturated fat intake of intervention children (mean (confidence interval)) (girls 11.9 (11.2-12.6) % of energy intake (E%); boys 12.5 (11.9-13.1)) was lower than that of the control children (girls 14.4 (13.7-15.2) E%; boys 15.0 (14.3-15. 8) E%) (P=0.0001 for the difference between intervention and control groups). The intake of unsaturated fat differed only slightly. Dietary ratios of polyunsaturated to saturated fatty acids (PS ratios) of the intervention and control diets were 0.44 and 0.33, respectively (P=0.0001). Furthermore, serum cholesterol concentrations of the intervention and control children differed (4. 28 (4.13-4.43) mmol/L vs 4.49 (4.35-4.63) mmol/L; P=0.04). Relative proportion of saturated fatty acids in serum TG was lower (34.9% vs 36.3%; P=0.04) and that of n-6 polyunsaturated fatty acids higher (13.9% vs 12.4%; P=0.0004) in the intervention than in the control children, whereas serum CE and PL fatty acid compositions of intervention and control groups were closely similar. However, intake of linoleic acid correlated better with serum linoleic acid relative content in the CE fraction (r=0.36; P=0.0001) than in the PL (r=0.27; P=0.0002) or in the TG (r=0.23; P=0.0016) fraction.Intervention resulted in decreased intake of saturated fatty acids and lowered serum total and LDL cholesterol concentrations. Of serum lipid fractions, TG fatty acid composition was the most sensitive and parallelled the findings in dietary food records.

Objective: To evaluate the contribution of the type of milk on serum cholesterol ester fatty acids in infants receiving mixed feeding, we analyzed 3-day dietary records and serum cholesterol ester fatty acid composition of 397 seven-month-old infants. Study design: The infants received, in addition to solid food, only one type of milk: human milk (n = 218), a ready-to-use liquid formula (n = 139), a powdered formula (n = 33), or soy formula (n = 7). Results: Mean fat intakes were low and varied from 28% to 31% of energy; the milks provided 43% to 64% of the fat. The mean polyunsaturated/saturated fat ratios of solid foods were from 0.52 to 0.63 and of milks from 0.20 to 0.45. Breast-fed infants' relative serum linoleic acid (18:2n-6) concentration was low (51.2%), whereas infants fed liquid formula had low serum oleic acid (18:1n-9) in accordance with low oleic acid content in that formula. The breast-fed infants had markedly higher serum concentrations of arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) than the infants fed any of the formulas. Conclusion: The typical fatty acid patterns of breast- or formula-fed infants were still evident in 7-month-old infants who already received 60% to 70% of their energy from solid food. Marked differences were seen also in the relative concentrations of docosahexaenoic acid and arachidonic acid despite their small contribution in cholesterol esters. (J Pediatr 1997;130:110-6)

We characterized the phospholipid inhibition of estradiol and progesterone binding to guinea-pig and human myometrial receptors. Of twelve compounds studied, phosphatidylinositol (PI), lysophosphatidic acid and lysophosphatidylcholine (lyso-PC) were the most active inhibitors (50% inhibition at 10−5 M). Lyso-PC with fatty acid chain length C14:0 inhibited ligand binding both to estrogen receptor (ER) and progesterone receptor (PR), C16:0 only to PR and C18:0 neither to ER nor to PR. The lyso-derivates were more inhibitory than the parent compounds. The ionic detergent (sodium taurocholate) inhibited both ER and PR binding, but the non-ionic detergent (Triton X-100) only PR. Triton X-100 enhanced the PI-induced inhibition of ER binding by a factor of 10. PR was more sensitive to inhibition than ER in all cases. The type of inhibition was non-competitive. At term pregnancy, ligand binding to myometrial ER or PR was low or absent in humans, but moderate in the guinea-pig. Phospholipid extracts of human decidua and fetal membranes contained PI and phosphatidylserine rather than lyso-PC. The extract was a potent inhibitor of ligand binding to PR (50% inhibition at 10−6 M phospholipid phosphorus), but not to ER. The physicochemical environment, modulated by phospholipids acting as detergents, may regulate sex steroid function also in vivo. This might have special significance for pregnancy maintenance.

The potential value of xylitol in calcium therapy was evaluated by comparing the effect of dietary xylitol (50 g/kg diet) + calcium carbonate with the effects of calcium carbonate, calcium lactate and calcium citrate on bone repair of young male rats after the rats consumed for 3 wk a calcium-deficient diet (0.2 g Ca/kg diet). After this calcium-depletion period, the rats were fed for 2 wk one of four diets, each containing 5 g Ca/kg diet as one of the four dietary calcium sources. The diet of the control animals was supplemented with CaCO3 (5 g Ca/kg diet) throughout the study. The Ca-deficient rats showed low bone mass, low serum calcium and high serum 1,25-dihydroxycholecalciferol, parathyroid hormone (1-34 fraction) and osteocalcin concentrations. They also excreted magnesium, phosphate and hydroxyproline in the urine in high concentrations, and had high bone alkaline phosphatase and tartrate-resistant acid phosphatase activities. Most of these changes were reversed by the administered of the calcium salts. The highest recoveries of femoral dry weight, calcium, magnesium and phosphate were observed in the groups receiving xylitol+CaCO3 and calcium lactate. Calcium lactate and calcium citrate caused low serum phosphate concentration compared with rats receiving CaCO3 and with the age-matched Ca-replete controls. Xylitol-treated rats excreted more calcium and magnesium in urine than did the other rats, probably due to increased absorption of these minerals from the gut. These results suggest that dietary xylitol improves the bioavailability of calcium salts.

Previous studies have shown that xylitol, the five-carbon sugar alcohol, increases the intestinal absorption of Ca in the rat. In this study an optimum xylitol:Ca molar ratio for Ca absorption and retention was determined in 10-week-old Long-Evans male rats. Xylitol was intubated with 20 mg of 45Ca (as 45CaCl2 or 45CaCO3) into the stomach of fasted rats in 1 ml water using xylitol:Ca molar ratios of 0:1, 0.5:1, 1:1, 1.5:1 or 2:1. Radioactivity of urine, feces and humerus was determined from 48-hr samples. The highest retention rate of 45Ca in the whole body or in the humerus was found when 114 mg of xylitol was given with Ca (xylitol:Ca molar ratio 1.5). Xylitol affected humeral retention more significantly than whole body retention. For comparison, the retention of 45Ca was determined from four lactose:CaCl2 combinations and from Ca-lactate and Ca-citrate salts. None of these combinations increased Ca retention significantly, although lactose at 114 mg dose showed slight positive effect. The results favor the use of a xylitol:Ca molar ratio of 1.5 in Ca supplements.

The therapeutic value of three calcium absorption promoting carbohydrates, lactose, gluconate and xylitol, in bone calcification was evaluated in 7-week-old male rats which were fed on a semisynthetic Ca-deficient diet for 3 weeks. Lactose + CaCO3, xylitol + CaCO3, Ca-gluconate, or CaCO3 alone were administered to the Ca-deficient rats for 2 weeks; the carbohydrate and Ca contents of the diets were 5% and 0.5%, respectively. The Ca-deficient rats showed a decrease in serum total Ca and ionized Ca2+ and in tibial Ca, Mg, P and density, with a concomitant increase in bone hydroxyproline concentration. Bone and serum tartrate-resistant acid phosphatase activities were increased 2-fold and the serum 1,25(OH)2D3 level 5-fold. Smaller increases were found in serum calcitonin, PTH, alkaline phosphatase and osteocalcin levels. These changes (except calcitonin) were reversed by the administration of Ca and the carbohydrates. It was observed that all three agents improved the recalcification of bones compared with the effect of CaCO3 alone. The effect of lactose and xylitol was superior to that of gluconate. These results suggest advantages in the use of xylitol in Ca-supplements.

Groups of 12 Long-Evans male rats were exposed to diets containing 20% galactitol (G), mannitol (M) or xylitol (X) for 5 wk. Serum electrolyte concentrations were within normal ranges for rats in all groups compared to control rats. All polyol-fed animals exhibited diuresis and a lower urinary pH (6.2-5.3) with a concomitant lower excretion of Na+, Cl- and protein (40% of controls). The excretion of K+ was lower in the X-fed rats than in any other group. Urinary Ca2+ excretion was sixfold higher and Mg2+ excretion, twofold higher in all polyol-fed rats than in controls. PO4 and NH4+ excretions were higher than controls in G- and M-fed animals only. Serum aldosterone concentrations in all polyol rats were 60% of those in controls. The serum corticosterone and parathyroid hormone levels were normal. Urinary citric acid was significantly higher in rats fed polyols but oxalic acid excretion was either normal (X) or lower (G,M) than in controls. Concentrations of serum and liver iron were higher in polyol-fed rats than in controls. Nevertheless, the normal serum creatinine and electrolyte concentrations and normal urinary creatinine levels established healthy kidney function. The diuretic effect of the polyols was considered responsible for the changes in the monovalent ion metabolism. The alterations in the excretion of multivalent cations most likely resulted from their increased intestinal absorption facilitated by the general chelating action of these polyols.

The effect of dietary supplements of xylitol, sorbitol and glucose on bone composition was studied in rats. The supplementation, expressed as a % of the dry diet, was gradually increased up to 20% over 3 weeks and continued for 5 weeks. The control group was fed a stock diet only. Each group consisted of nine rats aged 12 weeks at the beginning of the experiment. Ca, Mg, P, CO3 and citrate were analysed from the femur and Ca and citrate also from the serum and urine. The results showed that xylitol supplementation significantly increased the concentrations of Ca and citrate in bone (P less than 0.001) and sorbitol that of Ca only, whereas glucose slightly reduced both CO3 and citrate. The citrate concentration was found to correlate significantly with Ca and P (P less than 0.001), and also with Mg (P less than 0.002). Both xylitol and sorbitol increased serum Ca and the urinary excretion of Ca and citrate. In conclusion, high xylitol or sorbitol supplementation affects Ca and citrate metabolism. The results suggest a connection between citrate and Ca in bone.

The acidification of urine during polyol feeding was investigated with 27 Long-Evans male rats (aged 12 weeks) which were fed a xylitol diet (X), a sorbitol diet (S), or a basal diet for 4 weeks. The amount of polyols in the diet was increased from 5% to the final 20% level within 3 weeks. The polyol-fed animals showed reduced weight gain, lowered urine pH (from 6.5 to 5.6), and a 4-fold increase in the titratable acid excretion. X and S increased the daily urine volumes by 49 and 63%, respectively, but did not affect the wet weight or the pH values of the feces. Gas chromatographic-mass spectrometric analyses of organic acids revealed highly increased amounts of methylmalonic acid (13- to 20-fold) and 2-oxoglutaric acid (4- to 5-fold) in the urine of polyol-fed rats. The urinary excretion of citric acid and malic acid was also increased significantly (2- to 4-fold). The acidity of urine was not reflected in the blood acid-base balance of the animals. The increases in the levels of urinary organic acids in the polyol-fed rats were explained in terms of impaired mitochondrial oxidation of these acids and of impaired conversion of methylmalonic acid to succinic acid.

Sucrose consumption data of the sucrose group (n = 33) of a 2-yr longitudinal study was plotted against salivary sucrase activity values obtained during this 2-yr period. The correlation coefficients varied between 0.194 and 0.551. The subjects were divided into high (greater than or equal to 10 mumol x min-1 x (10(-3)) and low (less than 10) sucrase activity subgroups. There were significant differences in the sucrose consumption and in intake frequency between these two subgroups. These findings give further support for the possibility of using sucrase activity for the estimation of the level of individual sugar consumption.

The effect of peroral administration of xylitol (5% or 20% in food) on adrenal function was investigated in thirty-five Long-Evans male rats. The control rats were fed either a non-substituted stock diet or a 20% glucose diet. Glucose elevated and 20% xylitol reduced the growth of the rats (P less than 0.001), but 5% xylitol had no effect on the body weight. The concentrations of serum glucose and lactic acid decreased in rats fed 20% and 5% xylitol, respectively, but those of insulin, glucagon, corticosterone and aldosterone were not affected. In the adrenal glands, 20% xylitol loading was associated with increased epinephrine (P less than 0.05) and norepinephrine (P less than 0.001), but with decreased aldosterone (P less than 0.001) concentrations. The weights and histological picture of adrenal glands were normal. The urinary pH of xylitol-fed rats decreased significantly (P less than 0.01). Although peroral xylitol affected the levels of aldosterone and catecholamines, a normal glucocorticoid metabolism was permitted. The reduced aldosterone levels were regarded as secondary reactions, possibly resulting from alterations in electrolyte and/or acid-base balance. The increased catecholamine synthesis may be associated with the promoting effect of xylitol on intestinal calcium absorption.

1. The effect of xylitol feeding on the iron content of rat tissues was studied.2. Adult male rats were fed on the basal diet containing (g/kg) 200 glucose, or 50 or 200 xylitol, or the same diet containing no added carbohydrates for 8 weeks. Each feeding group comprised nine animals.3. Xylitol at 200 g/kg diet retarded the growth rate of the rats, whereas 200 g glucose/kg increased the weight gains compared with animals given no added carbohydrates.4. Xylitol at 50 g/kg did not affect the tissue Fe concentrations, but 200 g xylitol/kg increased the Fe content of the livers, duodenum wall, spleen, bone marrow and serum.5. Cadmium and lead contents of the livers were similar in all groups.6. Xylitol–Fe complexes are suggested to be responsible for the increased Fe absorption during xylitol feeding.

Rats were given xylitol (X) or glucose (G) in drinking water for a period of 28-33 days of which the last 2 days also comprised intake of 14C(U)-X or -G. Samples of plasma, liver, kidneys, pancreas, duodenum and the parotid, submandibular and lacrimal glands were homogenized and separated into various fractions for radioactivity and chemical analyses. The X-fed animals had smaller lacrimal and submandibular glands than the G-fed siblings. The radioactivities of the plasma, liver and kidney trichloroacetic acid extracts of both sexes increased more in the X-groups. X increased the incorporation of the label into the total lipids of plasma, liver and duodenum in both sexes. In males, X increased the labeling of both the neutral lipids and phospholipids. In females, X increased plasma lysolecithin and decreased plasma lecithin. The organs of the X-fed females contained less ascorbic acid than those of the G-fed animals, except for plasma and the parotid glands. Several organs of the males also showed this phenomenon. X and G thus exerted selective effects on the exocrine glands. Although X entered easily the regular G metabolism and acted as a physiological carbon source, the incorporation of labeled X was, however, sex-dependent. The relationship between peroral xylitol and the metabolism of phospholipids and ascorbic acid should be especially considered in rats.

1. The effect of peroral administration of xylitol on the absorption of iron and the activities of xanthine oxidase (EC 1. 2. 3. 2) and ferroxidase in rat duodenal wall was studied.2. Adult male rats were given the basal diet containing 200 g xylitol/kg or the same diet containing no added carbohydrates for 8 weeks. Both feeding groups comprised twelve animals.3. Xylitol significantly increased serum and liver Fe concentrations with a concomitant, significant increase in the duodenal xanthine oxidase activities, but caused a marginal increase in the duodenal ferroxidase activities.4. In vitro, sugar alcohols reduced the binding rate of Fe to transferrin.5. The xylitol-induced increase of Fe absorption may involve the following mechanism: the high intraluminal xylitol concentration of the xylitol-fed rats keeps Fe in the form of a soluble complex for a prolonged period of time, due to the slow absorption of xylitol. The polyol-Fe complex in turn induces xanthine oxidase and ferroxidase formation.

Sir, Boelsterli and Zbinden (1985) reported in this journal on biochemical and morphological changes of the rat adrenal medulla induced by xylitol. This paper was interesting, multifaceted and it elucidated an important biomedical issue related to xylitol which is becoming a leading nutritive sucrose substitute by virtue of its noncariogenicity and anticariogenicity, and its suitability in the diabetic diet. Although the methodology and the presentation of data of the above paper were by and large impeccable, we oppose the authors' view, presented in their Discussion, that peroral administration of xylitol would cause hyperinsulinemia and hypoglycemia. Our perusal of the study of Boelsterli and Zbinden showed that some of the data presented does not justify the conclusions made. Our view is based on the following methodological features and conclusions of their study.

The effect of feeding high amounts of polyols on rat metabolism was studied. Adult male rats were fed the basal diet or the same diet to which had been added either galactitol, mannitol or xylitol for 8 wk (final polyol level 200 g/kg diet). Although all three polyols retarded the growth rate of the animals, the polyols were well tolerated. The four experimental groups did not differ significantly (P greater than 0.01) in the following analyses: blood lactic acid and serum transaminases, amylase, lactate dehydrogenase, triglycerides, insulin, glucagon and corticosterone. Compared to rats fed the basal diet, galactitol rats had higher blood hemoglobin levels (P less than 0.01); those fed galactitol or mannitol had lower blood glucose (P less than 0.001 and P less than 0.01, respectively), and those fed mannitol had higher blood pyruvic acid (P less than 0.01). Rats fed any of the polyols had lower serum total cholesterol and liver ascorbic acid (P less than 0.001) than control rats. Rats fed mannitol had higher liver glycogen levels (P less than 0.001) than control rats. Irrespective of the structural differences between the pentitol and the hexitols, a number of common metabolic effects were found. The proposed mechanisms of these effects include 1) the slow absorption and the rapid intraluminal metabolism of the polyols and 2) the similar handling of these polyols in the liver by a dehydrogenase.

The structure-based design of a mutant form of the thromboxane A 2 prostanoid receptor (TP) was instrumental in characterizing the structural determinants of the hetero-dimerization process of this G protein coupled receptor (GPCR). The results suggest that the heterodimeric complexes between the TPα and β isoforms are characterized by contacts between hydrophobic residues in helix 1 from both monomers. Functional characterization confirms that TPα-TPβ hetero-dimerization serves to regulate TPα function through agonist-induced internalization, with important implications in cardiovascular homeostasis. The integrated approach employed in this study can be adopted to gain structural and functional insights into the dimerization/oligomerization process of all GPCRs for which the structural model of the monomer can be achieved at reasonable atomic resolution. © Springer Basel AG 2010.

Water-in-salt solutions, i.e. solutions in which the amount of salt by volume or weight is larger than that of the solvent, are attracting increasing attention in electrochemistry due to their distinct features that often include decomposition potentials much higher than those of lower concentration solutions. Despite the high solubility of potassium acetate (KAC) in water at room temperature (up to 25 moles of salt per kg of solvent), the low cost, and the large availability, the use of highly concentrated KAC solutions is still limited to a few examples in energy storage applications and a systematic study of their physical-chemical properties is lacking. To fill this gap, we have investigated the thermal, rheological, electrical, electrochemical, and spectroscopic features of KAC/water solutions in the compositional range between 1 and 25 mol kg-1. We show the presence of a transition between the "salt-in-solvent" and "solvent-in-salt" regimes in the range of 10-15 mol kg-1. Among the explored compositions, the highest concentrations (20 and 25 mol kg-1) exhibit good room temperature conductivity values (55.6 and 31 mS cm-1, respectively) and a large electrochemical potential window (above 2.5 V).

The sensitization of scintillation in polymeric composites based on fluorescent nanocomplexes. The archive contains 5 text files (including this annotation.txt) and one pdf file (ESI of the paper): 1. Annotation.txt (this file) 2. Nanomat_Scint_Sensitization_figure 2_Absorption_PL_TRPL _ energy transfer yield rate_Au8 superstructures and rhodamine 6G.TXT 3. Nanomat_Scint_Sensitization_figure 3_ RL spectra of the composite series as function of the emitter Rh6G concentration.txt 4. README Nanomat_scint.txt- where 2,3 files are described 5. nanomaterials-ESI.zip In this paper, the sensitization of scintillation was investigated in crosslinked polymeric composite materials loaded with luminescent gold clusters aggregates acting as sensitizers, and with rhodamine 6G as emitting dye. The findings enabled to give an expression of the sensitization efficacy as a function of the characteristic parameters of the employed luminescent systems and offer a guideline for the realization of composite materials with maximized sensitization effect. The name of the individual files is a short description of the content that has been explained with details in README.txt. All files are collected in one directory. The file 'README Nanomat_scint.txt' contains short description of the individual files.

Simple Summary Despite success of targeted therapy, cancer cells very often find a way to survive treatment; this eventually causes a tumor to relapse. In a particular type of lymphoma carrying a specific chromosomal rearrangement named anaplastic large-cell lymphoma (ALCL), selective drugs targeting the cause of the disease can induce spectacular remission of chemotherapy-resistant cancer. However, the lymphoma relapses again in about half of the cases, leaving no therapeutic options. We studied the possibility to combine two simultaneous treatments in order to prevent the relapse, starting from the hypothesis that acquiring resistance to two drugs at the same time is statistically very unlikely. We demonstrate that treating lymphoma cells with drug combinations has superior efficacy in comparison with single drug treatments, both in cell cultures and in mice. Abstract Anaplastic lymphoma kinase-positive (ALK+) anaplastic large-cell lymphoma (ALCL) is a subtype of non-Hodgkin lymphoma characterized by expression of the oncogenic NPM/ALK fusion protein. When resistant or relapsed to front-line chemotherapy, ALK+ ALCL prognosis is very poor. In these patients, the ALK inhibitor crizotinib achieves high response rates, however 30–40% of them develop further resistance to crizotinib monotherapy, indicating that new therapeutic approaches are needed in this population. We here investigated the efficacy of upfront rational drug combinations to prevent the rise of resistant ALCL, in vitro and in vivo. Different combinations of crizotinib with CHOP chemotherapy, decitabine and trametinib, or with second-generation ALK inhibitors, were investigated. We found that in most cases combined treatments completely suppressed the emergence of resistant cells and were more effective than single drugs in the long-term control of lymphoma cells expansion, by inducing deeper inhibition of oncogenic signaling and higher rates of apoptosis. Combinations showed strong synergism in different ALK-dependent cell lines and better tumor growth inhibition in mice. We propose that drug combinations that include an ALK inhibitor should be considered for first-line treatments in ALK+ ALCL.

Sensitized triplet-triplet annihilation-based photon upconversion is a photo-physical process that affords anti-Stokes-shifted emission after annihilation of two metastable triplet excitons of an emitter dye and the formation of a fluorescent singlet state. While this process readily occurs in solutions under conditions where the mobility of the dye molecules is high, particular architectures are required to facilitate efficient energy transfers in solid polymers. One possibility is to incorporate liquid upconverting domains into solid polymer matrices. Another possibility is to reduce the intermolecular distance between the dyes below the Dexter radius, allowing exciton migration via triplet hopping. We introduce herein nanostructured materials that combine both of these features. These glassy nanostructured polymer systems contain liquid upconverting nanodroplets that are stabilized with a block copolymer surfactant and are fabricated under ambient conditions in a facile one-step protocol. The dyes concentrate in the nanostructured liquid domains, and this enables hopping-mediated ET and TTA between the dyes and leads to an upconversion efficiency of similar to 20%.

The dynamics of xenon gas, loaded in a series of 1-alkyl-3-methylimidazolium based ionic liquids, probes the formation of increasingly blurred polar/apolar nanodomains as a function of the anion type and the cation chain length. Exploiting 129 Xe NMR spectroscopy techniques, like Pulse Gradient Spin Echo (PGSE) and inversion recovery (IR), the diffusion motion and relaxation times are determined for 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [Cn C1 im][TFSI]. A correlation between the ILs nano-structure and both xenon diffusivity and relaxation times, as well as chemical shifts, is outlined. Interestingly, comparison with previous results of the same properties in the homologous imidazolium chlorides and hexafluorophospate shows an opposite trend with the alkyl chain length. Classical molecular dynamics (MD) simulations are used to calculate the xenon and cation and anion diffusion coefficients in the same systems, including imidazolium cations with longer chains (n=4, 6, 8 … 20). An almost quantitative agreement with the experiments validates the MD simulations and, at the same time, provides the necessary structural and dynamic microscopic insights on the nano-segregation and diffusion of xenon in bistriflimide, chloride and hexafluorphosphate salts allowing to observe and rationalize the shaping effect of the cation in the nanostructure.

Ionic liquid (IL) mixtures enable the design of fluids with finely tuned structural and physicochemical properties for myriad applications. In order to rationally develop and design IL mixtures with the desired properties, a thorough understanding of the structural origins of their physicochemical properties and the thermodynamics of mixing needs to be developed. To elucidate the structural origins of the excess molar volume within IL mixtures containing ions with different alkyl chain lengths, 3 IL mixtures containing 1-alkyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ILs have been explored in a joint small angle X-ray scattering (SAXS) and 129Xe NMR study. The apolar domains of the IL mixtures were shown to possess similar dimensions to the largest alkyl chain of the mixture with the size evolution determined by whether the shorter alkyl chain was able to interact with the apolar domain. 129Xe NMR results illustrated that the origin of excess molar volume in these mixtures was due to fluctuations within these apolar domains arising from alkyl chain mismatch, with the formation of a greater number of smaller voids within the IL structure. These results indicate that free volume effects for these types of mixtures can be predicted from simple considerations of IL structure and that the structural basis for the formation of excess molar volume in these mixtures is substantially different to IL mixtures formed of different types of ions.

The formation of block copolymer nanoparticles is commonly obtained by switching solvent quality from good solvent for both blocks to a selective solvent for one block. The effect of the selective solvent on particle dimension, shape and inner structure has been analyzed in detail, instead less attention has been focused on the role of the common solvent. Poly(ethylene oxide)-block-poly(lactic acid) (PEO-b-PLA) is widely used for the preparation of nanometric drug delivery systems and the control of the particle morphology has relevant effects on bioactivity. In this work we investigate the effect of using different common solvents (acetone, dioxane, tetrahydrofuran, dimethylformamide) on the self-assembly behavior of narrowly dispersed PEO-b-PLA copolymers, synthesized by metal free ring-opening polymerization, with large variation of molecular weight of the hydrophobic block (from 65 to 1300 lactic units). Dynamic light scattering (DLS) and cryo-electron microscopy (cryo-EM) analyses of PEO-b-PLA nanoparticles reveal that their size and shape are strongly dependent on the hydrogen bonding ability of the common solvent used in the self-assembly process. As consequence of these variations, also the cytoxicity of the nanoparticles is affected.

Developing new materials for the separation of gas mixtures is a key subject in setting up a circular economy. In this work, we report the synthesis and application of novel polymeric membranes, based on polymerized ionic liquids (PILs), to be used for CO2 separation from different gas pairs. Phosphonium-based PILs have been copolymerized within an original acrylate formulation that allowed the development of dense membranes able to overcome some of the main limitations related to ionic liquid membranes. Thereby, a collection of phosphonium ionic liquids has been investigated by evaluating the influence of the alkyl chain length and anion type on membrane structure and properties by employing a series of different chemo-physical characterization techniques. The membranes showed a marked preference toward CO2 permeation in the wet state, which simulates the conditions occurring with many CO2-containing gas streams, with two of the studied membranes exceeding the Robeson upper bound for the CO2/H2 gas pair.

Background: Several studies focused on the possible role of vitamin D (vitD) in pain chronicization.. The aim of this study was to assess the potential implications of VitD deficit on headache characteristics and extracranial pain extension.Methods: Eighty consecutive patients with primary headache underwent neurological examination, laboratory exams including serum calcifediol 25(OH)D and headache features assessment along with three questionnaires investigating depression, anxiety and allodynia. Results: The 82.6% of the population had migraine (48% episodic and 52% chronic form). The 45% of patients had extracranial pain and 47% suffered from allodynia. In the 45% of patients had a VitD deficit since the serum 25(OH)D levels fell below the cut-off level of 20 ng/ml. The occurrence of VitD deficit was significantly higher (p=0.009) in patients suffering from chronic migraine (CM)- medication overuse migraine (MOH) (64.7%) than in episodic migraine (EM) or tension type headache (TTH). The occurrence of subjects with extracranial pain and allodynia was higher, as expected, in the CM-MOH than in the EM and in the TTH groups but was not related to the co-occurrence of vit-D deficiency (Fischer’s exact test p=0.11 and p=0.32 respectively).Conclusions: Our findings show that 25(OH)D deficit is related to chronic pain suggesting that vitD probably has anti-inflammatory and tolerogenic properties, rather than a direct antinociceptive effect, and reinforce the idea of a neuroinflammatory mechanisms underpinning migraine chronicization.

Photon upconversion based on sensitized triplet–triplet annihilation (sTTA-UC) is a wavelength-shifting technique with potential use in actuators, sensing, and solar technologies. In sTTA-UC, the upconverted photons are the result of radiative recombination of high-energy singlets, which are created through the fusion of metastable triplets of two annihilator/emitter molecules. The emitter triplets are populated via energy transfer (ET) from a low-energy absorbing light-harvester/sensitizer. The process is highly efficient at low powers in solution but becomes relatively ineffective in solid matrices since the limited molecular mobility precludes bimolecular interactions. The realization of efficient solid-state upconverters that exhibit long-term stability and are compatible with industrial fabrication processes is an open challenge. Here, nanophase-separated polymer systems synthesized under ambient conditions that contain the upconverting dyes in liquid nanodomains is reported. The nanostructured polymers show an excellent optical quality, an outstanding upconversion efficiency of up to ≈23%, and excellent stability in air, with only negligible performance losses over a period of three months. Moreover, the dyes’ confinement in nanosized domains

The translational dynamics of xenon gas dissolved in room-temperature ionic liquids (RTILs) is revealed by 129Xe NMR and molecular dynamics (MD) simulations. The dynamic behavior of xenon gas loaded in 1-alkyl-3-methylimidazolium chloride, [CnC1im]Cl (n = 6, 8, 10), and hexafluorophosphate, [CnC1im][PF6] (n = 4, 6, 8, 10) has been determined by measuring the 129Xe diffusion coefficients and NMR relaxation times. The analysis of the experimental NMR data demonstrates that, in these representative classes of ionic liquids, xenon motion is influenced by the length of the cation alkyl chain and anion type. 129Xe spin-lattice relaxation times are well described with a monoexponential function, indicating that xenon gas in ILs effectively experiences a single average environment. These experimental results can be rationalized based on the analysis of classical MD trajectories. The mechanism described here can be particularly useful in understanding the separation and adsorption properties of RTILs.

Lithium Metal Batteries (LMB) require solid or quasi-solid electrolytes able to block dendrites formation during cell cycling. Polymer-in-ceramic nanocomposites with the ceramic fraction exceeding the one normally used as the filler (>10 ÷ 15 wt%) are among the most interesting options on the table. Here, we report on a new hybrid material encompassing brush-like TiO2 nanocrystals functionalized with low molecular weight poly(ethylene oxide) (PEO). The nanocomposite electrolyte membranes are then obtained by blending the brush-like nanocrystals with high molecular weight PEO and LiTFSI. The intrinsic chemical compatibility among the PEO moieties allows a TiO2 content as high as ∼39 wt% (90:10 w/w functionalized nanocrystals/PEO-LiTFSI), while maintaining good processability and mechanical resistance. The 50:50 w/w nanocomposite electrolyte (18.8 wt% functionalized TiO2) displays ionic conductivity of 3 × 10−4 S cm−1 at 70 °C. Stripping/plating experiments show an excellent long-term behavior even at relatively high currents of 200 μA cm−2. Upon testing in a lab-scale Li/electrolyte/LiFePO4 cell, the material delivers 130 mAh g−1 and 120 mAh g−1 after 40 and 50 cycles at 0.05 and 0.1 mA, respectively, with Coulombic efficiency exceeding 99.5%, which demonstrates the very promising prospects of these newly developed nanocomposite solid electrolyte for future development of LMBs.

Recurrent somatic mutations in ETNK1 (Ethanolamine-Kinase-1) were identified in several myeloid malignancies and are responsible for a reduced enzymatic activity. Here, we demonstrate in primary leukemic cells and in cell lines that mutated ETNK1 causes a significant increase in mitochondrial activity, ROS production, and Histone H2AX phosphorylation, ultimately driving the increased accumulation of new mutations. We also show that phosphoethanolamine, the metabolic product of ETNK1, negatively controls mitochondrial activity through a direct competition with succinate at mitochondrial complex II. Hence, reduced intracellular phosphoethanolamine causes mitochondria hyperactivation, ROS production, and DNA damage. Treatment with phosphoethanolamine is able to counteract complex II hyperactivation and to restore a normal phenotype., ETNK1 mutations are recurrent in leukemia but how they contribute to oncogenesis is still unclear. Here, the authors show that ETNK1 mutations increase mitochondrial activity, ROS and H2AX levels and that these effects can be rescued upon phosphoethanolamine supplementation.

Polyunsaturated fatty acids (PUFAs) biostatus has been proposed as possible attention deficit hyperactivity disorder (ADHD) diagnosis biomarker. The present exploratory study aimed to investigate the association between PUFAs biostatus and cerebral cortex metabolism measured by functional Near Infrared Spectroscopy (fNIRS) in a sample of children with and without ADHD. 24 children with ADHD and 22 typically developing (TD) peers, aged 8&ndash, 14, were recruited. Linoleic, arachidonic, docosahexaenoic and eicosapentaenoic acids levels were evaluated in whole blood. All children underwent fNIRS while performing an n-back working memory task. Between groups comparisons revealed lower levels of arachidonic acid in children with ADHD and stronger NIRS signal in TD participants, especially when completing more difficult tasks. Correlations conducted between fNIRS activation and PUFA biostatus revealed several associations between hemodynamic changes in the frontoparietal regions and fatty acids profile across participants. This result was also confirmed by the multiple hierarchical regression analyses that remarked an inverse effect of eicosapentaenoic acid levels on oxyhemoglobin values in right frontoparietal region. Such preliminary findings, if confirmed, would suggest that PUFAs could play a role in atypical neurodevelopment.

Diels-Alder chemistry has been used for the thermoreversible cross-linking of furan-functionalized ethylene/propylene (EPM) and ethylene/vinyl acetate (EVM) rubbers. Both furan-functionalized elastomers were successfully cross-linked with bismaleimide to yield products with a similar cross-link density. NMR relaxometry and SAXS measurements both show that the apolar EPM-g-furan precursor contains phase-separated polar clusters and that cross-linking with polar bismaleimide occurs in these clusters. The heterogeneously cross-linked network of EPM-g-furan contrasts with the homogeneous network in the polar EVM-g-furan. The heterogeneous character of the cross-links in EPM-g-furan results in a relatively high Youngs modulus, whereas the more uniform cross-linking in EVM-g-furan results in a higher tensile strength and elongation at break.

Thromboxane A2 is a potent mediator of inflammation and platelet aggregation exerting its effects through the activation of a G protein-coupled receptor (GPCR), termed TP. Although the existence of dimers/oligomers in Class A GPCRs is widely accepted, their functional significance still remains controversial. Recently, we have shown that TPα and TPβ homo-/hetero-dimers interact through an interface of residues in transmembrane domain 1 (TM1) whose disruption impairs dimer formation. Here, biochemical and pharmacological characterization of this dimer deficient mutant (DDM) in living cells indicates a significant impairment in its response to agonists. Interestingly, two single loss-of-function TPα variants, namely W29C and N42S recently identified in two heterozygous patients affected by bleeding disorders, match some of the residues mutated in our DDM. These two naturally occurring variants display a reduced potency to TP agonists and are characterized by impaired dimer formation in transfected HEK-293T cells. These findings provide proofs that lack of homo-dimer formation is a crucial process for reduced TPα function in vivo, and might represent one molecular mechanism through which platelet TPα receptor dysfunction affects the patient(s) carrying these mutations.

Highly controlled polymers and nanostructures are increasingly translated from the lab to the industry. Together with the industrialization of complex systems from renewable sources, a paradigm change in the processing of plastics and rubbers is underway, requiring a new generation of analytical tools. Here, we present the recent developments in time domain NMR (TD-NMR), starting with an introduction of the methods. Several examples illustrate the new take on traditional issues like the measurement of crosslink density in vulcanized rubber or the monitoring of crystallization kinetics, as well as the unique information that can be extracted from multiphase, nanophase and composite materials. Generally, TD-NMR is capable of determining structural parameters that are in agreement with other techniques and with the final macroscopic properties of industrial interest, as well as reveal details on the local homogeneity that are difficult to obtain otherwise. Considering its moderate technical and space requirements of performing, TD-NMR is a good candidate for assisting product and process development in several applications throughout the rubber, plastics, composites and adhesives industry.

The sensitized triplet-triplet annihilation-based upconversion in bicomponent systems is currently considered the most promising strategy for increasing the light-harvesting ability of solar cells. Flexible, manageable, inexpensive up-converting devices become possible by implementing this process in elastomers. Here, we report a study combining optical spectroscopy data of the light conversion process with the nano- and macroscopic viscoelastic characterization of the host material embedding the active dyes, in order to find a rationale for the fabrication of efficient solid-state upconverting systems. By using the poly(n-alkyl acrylates) as a model of the monophasic elastomers, we demonstrate that the yield of the bimolecular interactions at the base of the upconversion process, namely, energy transfer and triplet-triplet annihilation, is mainly determined by the glass transition temperature (Tg) of the polymer. By employing the polyoctyl acrylate (Tg = 211 K), we achieved a conversion yield at the solid state larger than 10% at an irradiance of 1 sun, showing the potential of the elastomer-based upconverting materials for developing real-world devices.

Micro and mesoporous materials are often used in catalysis, purification, composite filler, and other applications. Almond shell is an important agricultural byproduct that can be transformed to microporous and mesoporous carbon. In this work, we produced biochar from almond shell using a thermal treatment procedure in an inert atmosphere and characterized the pores with nitrogen adsorption, environmental SEM, and 129Xe NMR. The latter technique differentiates adsorbed and nonadsorbed xenon and permits the correlation of different processing conditions with xenon adsorption and diffusivity. The relevance of removing the ash produced during the charring process has been included in the study. Moreover, the xenon exchange between meso- and micro-pores has been directly observed by 129Xe NMR, demonstrating that after ash removal by water the materials have high accessibility of the pores by external fluids, thus increasing the usefulness as filtration or adsorption material.

Shortly after processing, Polyethylene/Polypropylene (PE/PP) multilayer films demonstrate an increase in tensile modulus and other mechanical properties when the individual layer thickness is below 0.5 μm. Subsequent annealing at 60 °C for 16 h brings the properties of all other samples to similar values. WAXD characterization of the layered films identified a prevalence of mesophase in the thicker PP layers. In samples with increased layer numerosity or subjected to annealing, WAXD detected its conversion to α crystalline phase that correlates with improved mechanical properties. SSNMR and DSC detailed the defective nature of α iPP crystallites. Comonomers, detected by NMR in the commercial polymers used for the films, are the source of "tunable disorder" that dictates the formation of the PP mesophase and the low temperature of conversion to the mechanically stronger defective α phase. Soft intrafilm layer interfaces instead enable nucleation and localized polymer chain rearrangement even without annealing

Nanocrystals (NCs) surface characterization is a fundamental step for understanding the physical and chemical phenomena involved at the nanoscale. Surface energy and chemistry depend on particle size and composition, and, in turn, determine the interaction of NCs with the surrounding environment, their properties and stability, and the feasibility of nanocomposites. This work aims at extracting more information on the surface of different titanium dioxide polymorphs using1H-TD-NMR of water. Taking advantage of the interaction between water molecules and titanium dioxide NCs, it is possible to correlate the proton transverse relaxation times (T2) as the function of the concentration and the specific surface area (δp·Cm) and use it as an indicator of the crystal phase. Examples of three different crystals phase, rutile, anatase, and brookite, have been finely characterized and their behavior in water solution have been studied with TD-NMR. The results show a linear correlation between relaxivity (R2) and their concentration Cm. The resulting slopes, after normalization for the specific surface, represent the surface/water interaction and range from 1.28 g m-2s-1of 50 nm rutile nanocrystals to 0.52 for similar sized brookite. Even higher slopes (1.85) characterize smaller rutile NCs, in qualitative accordance with the trends of surface energy. Thanks to proton relaxation phenomena that occur at the NCs surface, it is possible to differentiate the crystal phase and the specific surface area of titanium dioxide polymorphs in water solution.