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• Development of a green method for epoxy resin synthesis. • Valorization of waste flours and mixed organic waste. • epoxidation of the precursors through UV/ozone exposure, without organic solvents. This paper reports the preparation of newly synthesized bio-epoxy monomers, suitable for replacing petrochemical-derived epoxy resins. An original green method able to produce epoxy monomers starting from neat carbohydrates, waste flours, and even from the organic fraction of municipal solid waste (OFMSW), was here proposed. Hence, for the first time, the epoxidation of carbohydrates was attained only through the exposition to UV and ozone radiation, without using any organic solvent to carry out the reaction. Besides the innovation in the epoxidation method, this work explored the possibility of valorizing waste materials, by recycling carbohydrate scraps; in particular, the exposition of waste flours and municipal solid waste to UV and ozone and their consequent epoxidation allowed obtaining green precursors for the production of a bio-based epoxy resin. Applicability and suitability of the synthesized compounds for epoxy monomers were investigated by curing experiments with a selected amount of a model cycloaliphatic amine-type hardener, i.e. isophorodiamine (IPDA). [ABSTRACT FROM AUTHOR]

Abstract This work is aimed to study the effect of cardanol derived plasticizers on the tensile modulus of poly(lactic acid), PLA. Neat cardanol, cardanol acetate (CA), and epoxidized cardanol acetate (ECA) were used, at contents ranging between 10% and 30%. For comparison purposes, another green plasticizer, poly(ethylene glycole) (PEG), was used. Tensile tests were carried out to evaluate the influence of the type and the amount of plasticizer on the tensile modulus of injection molded PLA. Within the examined composition limits, PLA plasticized by cardanol derivatives showed lower modulus than PEG plasticized PLA. The tensile modulus of plasticized PLA was correlated to the evolution of glass transition temperature and degree of crystallinity. At low plasticizers content, the modulus of PLA decreased as the glass transition temperature decreased, due to a better miscibility of the plasticizer with PLA. The opposite occurred at high plasticizer content; in this case, the higher modulus found for more compatible plasticizers were attributed to an increased crystallization kinetic. The evolution of elastic modulus as a function of glass transition temperature and degree of crystallinity was analyzed using a single equation capable to fit the data obtained using different plasticizers. Highlights • Cardanol derivatives were used for plasticization of poly(lactic acid). • Some cardanol derivatives had a plasticizing effectiveness higher than that of PEG. • This involved a decrease of the modulus and increase of ductility and toughness. • The higher plasticizing effectiveness is due to reduced crystallization kinetics. [ABSTRACT FROM AUTHOR]

This work is aimed to the study of the thermal and UV stability of Poly Vinyl Chloride (PVC) plasticized by cardanol derivatives. To this purpose, soft PVC obtained by cardanol derivatives, as well as by commercial plasticizers, were subjected to different sources of degradation, i.e. thermal treatments and UV weathering, and characterized by means of the tensile tests. Analysis of variance (ANOVA) was used to highlight the statistical significance of the type of plasticizer and treatment of soft PVC on the mechanic properties. In particular, estimation of the retention index of different plasticizers to different sources of degradation allowed highlighting the better performances of PLACARD compared to the other commercial plasticizers. In absence on any relevant loss of plasticizer during thermal treatment or UV weathering, the change in mechanical properties was attributed to change in the chemical structure of PVC homopolymer, which was studied by FTIR analysis. It was shown that the better retention of property of soft PVC plasticized by PLACARD is due to a lower amount of thermal or UV activated degradation. Therefore, the results highlight that PLACARD plasticizer can also act as an efficient thermal and UV stabilizer, which could increase soft PVC durability and recyclability, and contribute to a reduction of the amount of thermal and UV stabilizers, with additional relevant effects on the toxicological and environmental impact of soft PVC. [ABSTRACT FROM AUTHOR]

[Display omitted] It is well demonstrated the key role of Eph-ephrin system, specifically of EphA2 receptor, in supporting tumor growth, invasion, metastasis and neovascularization. We previously identified FXR agonists as eligible antagonists of Eph-ephrin system. Herein we characterize new commercially available FXR (Farnesoid X Receptor) agonists as potential Eph ligands including Cilofexor, Nidufexor, Tropifexor, Turofexorate isopropyl and Vonafexor. Our exploration based on molecular modelling investigations and binding assays shows that Cilofexor binds specifically and reversibly to EphA2 receptor with a Ki value in the low micromolar range. Furthermore, Cilofexor interferes with the phosphorylation of EphA2 and the cell retraction and rounding in PC3 prostate cancer cells, both events depending on EphA2 activation. In conclusion, we can confirm that target hopping can be a successful approach to discover new moiety of protein–protein inhibitors. [ABSTRACT FROM AUTHOR]

This work is aimed to the development and property optimization of cardanol derived plasticizers. To this purpose, different plasticizers were produced though different epoxidation routes, characterized by low toxicological and environmental impact. The plasticizers are characterized by different yield of epoxidation of the alkyl chain double bonds. The properties of the cardanol derived plasticizers were compared to the properties of commercial plasticizers, either phthalates or natural derived. Mechanical properties of soft PVC plasticized by cardanol derivatives were shown to be comparable to those of PVC with commercial plasticizers. The plasticizing efficiency of cardanol derivatives was significantly improved by increasing the yield of epoxidation. Also, mechanical properties performed after ageing showed the excellent stability of the properties of the cardanol derived plasticizer characterized by the higher yield. Evaluation of the property retention index after ageing indicated that such plasticizers showed an improved stability of properties compared to other commercial plasticizer. The results obtained highlight the relevance of an high conversion of the double bonds into epoxies in order to produce high quality plasticizers. [ABSTRACT FROM AUTHOR]

Abstract: Neutron coincidence counting is the reference NDA technique used in nuclear safeguards to measure the mass of nuclear material in samples. For high-enriched uranium (HEU) samples active neutron interrogation is generally performed and the most common device used by nuclear inspectors is the Active Well Coincidence Counter (AWCC). Within her master thesis at the Polytechnic of Milan, the first author performed an intensive study on the characteristics and performances of the AWCC in order to assess the 235U mass in HEU oxide samples at the PERLA laboratory of JRC. The work has been summarised in this paper that starts with the optimisation of the use of AWCC for nuclear safeguards, describing the calibration procedure, reporting results of a series of verification measurements, summarising the performances that can be obtained with this instruments during inspections at fuel production plants and concluding with the discussion of uncertainties related to these measurements. [ABSTRACT FROM AUTHOR]

Objectives: Recently, jawbone osteonecrosis has been reported as a potential adverse effect of bisphosphonates administration. This paper considers and highlights histopathologic and radiologic features of this condition. Study design: Eleven patients, owing to unresponsiveness to conservative treatment and uncontrollable pain, underwent surgical resection of diseased jawbone after extensive hyperbaric oxygen therapy. A thorough clinical, laboratory, and imaging study was performed. Surgical specimens underwent histopathologic and immunohistochemical evaluation. Results: Computerized tomography (CT) scans showed increased bone density, periosteal reaction, and bone sequestration in advanced stages. With magnetic resonance imaging (MRI), exposed areas showed a low signal in T1- and T2-weighted and inversion recovery images, which suggests low water content and is histopathologically correlated with paucity in cells and vessels (osteonecrotic pattern). Unexposed diseased bone was characterized by T1 hypointensity and T2 and IR hyperintensity, which suggests high water content and inflammation, associated with hypercellularity, osteogenesis, and hypervascularity (osteomyelitic pattern). Conclusions: Diseased bone extends beyond the limits of the bone exposed in the oral cavity. Histopathologic examination correlated well with CT and MRI, which are the choice for the evaluation of bisphosphonate-associated jawbone osteonecrosis. [Copyright &y& Elsevier]

Abstract: The present study investigated whether proliferation of hippocampal progenitors is subject to circadian modulation. Mice were perfused using 3h intervals throughout the light–dark cycle and brains were stained for Ki-67. Since Ki-67 is not expressed during the G0 phase of the cell cycle, we expected a decline in Ki-67 expression at the moment cells synchronously exit the cell cycle. However, despite the fact that various hippocampal factors fluctuate across the day, the number of dividing cells remained constant. In a second experiment, we studied whether disturbance of normal sleep affected the stable rate in cell proliferation. Our data show that 12h of sleep deprivation during the light phase did not influence proliferating cell number. A third experiment investigated whether physical activity, a condition known to enhance hippocampal cell proliferation, caused an elevation of the steady baseline number of proliferating progenitors, or a peak directly following the active phase of the animals. Mice were housed with a running wheel for 9 days. On the last day, animals were sacrificed either directly before or directly after the active phase. Exercise significantly promoted cell proliferation and this effect appeared to be strongest directly after the active period and to disappear during the resting phase. Our data suggest that hippocampal cell proliferation is not synchronized under basal conditions and is unchanged by sleep deprivation. However, running affected cell proliferation differentially at two times of day. These data demonstrate that the steady rate in cell proliferation is not indispensable, but can be changed by behavioral activity. [Copyright &y& Elsevier]

This research paper is focused on the upscaling of previous studies of authors group about the stabilization, inertization and valorisation of the Organic Fraction of Municipal Solid Waste (OFMSW). The developed process first involves the development of an original process in order to transform the organic waste into an inert and sterilized material and, successive incorporation of the treated-OFMSW into a catalysed water soluble Urea Formaldehyde (UF) based resin. In particular, in this research work we report on the design and realization of a prototype platform able to produce inertized and valorised panels, starting from OFMSW. The platform is managed by Arduino-based electronic sections for controlling process parameters and integrated with user's recognition and product traceability system based on Radio Frequency Identification (RFID) technology. Several panels were produced, by transforming different amounts and typology of OFMSW, in order to select the best composition, as a compromise between the production of panels with adequate mechanical properties and the usage of the lowest UF resin content. Mechanical and thermal characterization of the realized products was performed looking at potential applications of the panel. Finally, the RFID-based traceability system, managed by a properly developed software platform, allows to identify and store in the database the enabled users which give the OFMSW in the machinery and to track the produced panels or bricks, by using suitable wide-band low-cost passive UHF tags, thereby ensuring targeted and optimal management of the re-use or storage of the valorised products. In particular, the proposed system includes an innovative ICT part that uses UHF RFID technology, low-cost sensors and a Cloud platform capable to manage all collected data related to both disposed waste and bricks produced by transformation procedure. [ABSTRACT FROM AUTHOR]

Background: Inositols (INOs) supplementation during pregnancy, specifically the combination of myo-inositol (MI) and D-chiro-inositol (DCI), has been reported to improve vascular parameters in women with gestational diabetes mellitus. We demonstrated previously that offspring born to pregnant mice lacking the endothelial nitric oxide synthase (eNOS+/-) gene have hypertension (HTN) as adults and, when fed a high-fat diet (HFD), develop a metabolic syndrome (MS) phenotype.Objective: Our aim was to evaluate whether INOs treatment in pregnancy complicated by MS improves the vascular and metabolic profile in mice offspring programmed in utero to develop HTN and MS.Materials and Methods: Heterozygous eNOS+/- mice fed an HFD manifest a MS phenotype. Female eNOS+/- mice with MS were bred with a wild-type (WT) male. On gestational day 1, pregnant females were randomly allocated to receive either a mixture of INOs (MI/DCI: 7.2/0.18 mg/mL) or water as placebo until delivery. The female offspring obtained were genotyped and categorized as: WT (genetically normal, with eNOS gene) and eNOS+/- offspring (genetically modified, heterozygous for eNOS gene). Both offspring developed in an abnormal uterine environment due to maternal MS. At 9-10 weeks of age, the offspring underwent a glucose tolerance test (GTT) and systolic blood pressure (SBP) measurement. The mice were then sacrificed, and the carotid arteries were isolated for evaluation of vascular responses. Responses to phenylephrine (PE), in the presence and absence of a nonspecific nitric oxide inhibitor (N-nitro-L-arginine methyl ester [L-NAME]), the vasodilator acetylcholine (ACh), and sodium nitroprusside (SNP) were assessed.Results: The GTT showed lower glucose levels in both eNOS+/-INOs (P = .03) and WT-INOs (P = .05) offspring born to MS dams on INOs supplementation compared to offspring born to untreated dams. SBP was higher in eNOS+/- offspring compared to WT (169 ± 7 vs 142 ± 9 mm Hg, respectively, P = .04) and INOs treatment decreased SBP in WT-INOs (110 ± 10 mm Hg, P = .01) but not in eNOS+/-INOs offspring. Maximal (%Max) contractile response to PE was higher in eNOS+/- offspring born to MS dams and was decreased in those born to MS dams treated with INOs (%Max, eNOS+/-, 123 ± 7 vs eNOS+/-INOs, 82 ± 11 mm Hg, P = .007). No differences were seen in PE contractile responses in WT offspring born to MS dams treated or not treated with INOs (WT, 92 ± 4 vs WT-INOs, 75 ± 7). The L-NAME response was decreased in eNOS+/-INOs and WT-INOs offspring compared to untreated ones. The ACh vasorelaxation was impaired in eNOS+/- and WT offspring born to MS dams, and maternal INOs treatment improved offspring vascular relaxation in both offspring (P = .01 and P = .03, respectively). No differences were seen in response to SNP.Conclusion: Inositols supplementation improved glucose tolerance, SBP, and vascular responses in adult eNOS+/- and WT offspring born to dams with MS. Interestingly, WT born to MS dams show an altered vascular profile similar to eNOS+/- offspring and exhibit an improved response to INOs treatment. Our findings suggest that the benefits of INOs treatment are more pronounced in offspring exposed to environmental factors in utero, and less likely in those due to genetic factors. [ABSTRACT FROM AUTHOR]

Background: Myoinositol and D-chiroinositol improve insulin resistance in women with obesity and gestational diabetes and in postmenopausal women with metabolic syndrome. We previously reported that offspring born to hypertensive dams lacking endothelial nitric oxide synthase and fed a high-fat diet develop metabolic-like syndrome phenotype.Objective: The objective of the study was to investigate the effect of a mixture of myoinositol/D-chiroinositol supplementation during pregnancy on the maternal metabolic profile in pregnancies complicated by the metabolic-like syndrome and obesity using a pregnant mouse model.Study Design: Female heterozygous endothelial nitric oxide synthase(-/+) mice with moderate hypertension were placed on a high-fat diet for 4 weeks to induce a metabolic-like syndrome phenotype. Similarly, wild-type C57BL/6 mice were placed on a high-fat diet for 4 weeks to induce a murine obesity model. Mice were then bred with wild-type males. On gestational day 1, dams were randomly allocated to receive either a mixture of myoinositol/D-chiroinositol in water (7.2/0.18 mg/mL, respectively) or water as control (placebo). At term (gestational day 18), maternal weights, systolic blood pressure, and a glucose tolerance test were obtained. Dams were then killed; pups and placentas were weighed and maternal blood collected. Serum levels of metabolic biomarkers relevant to diabetes and obesity (ghrelin, gastric inhibitory peptide, glucagon-like peptide 1, glucagon, insulin, leptin, resistin) were measured by a multiplex enzyme-linked immunosorbent assay. Analysis was done comparing metabolic-like syndrome-myoinositol/D-chiroinositol-treated vs metabolic-like syndrome-nontreated mice and obese-myoinositol/D-chiroinositol-treated vs obese nontreated mice.Results: Mean systolic blood pressure was lower in metabolic-like syndrome pregnant mice treated with myoinositol/D-chiroinositol compared with placebo (P = .04), whereas there was no difference in systolic blood pressure between treated and placebo-treated obese pregnant mice. Pregnant metabolic-like syndrome mice treated with myoinositol/D-chiroinositol showed lower glucose values during the glucose tolerance test and in the area under the curve (myoinositol/D-chiroinositol: 17512.5 ± 3984.4 vs placebo: 29687.14 ± 8258.7; P = .003), but no differences were seen in the obese pregnant mice. Leptin serum levels were lower in the metabolic-like syndrome-myoinositol/D-chiroinositol-treated mice compared with the placebo group (myoinositol/D-chiroinositol: 16985 ± 976.4 pg/dL vs placebo: 24181.9 ± 3128.2 pg/dL, P = .045). No other differences were seen in any of the remaining serum metabolic biomarkers studied in metabolic-like syndrome and in obese pregnant mice. Maternal weight gain was not different in the pregnant metabolic-like syndrome dams, whereas it was lower in the obese myoinositol/D-chiroinositol-treated dams compared with the placebo group (myoinositol/D-chiroinositol: 10.9 ± 0.5 g vs 12.6 ± 0.6 g, P = .04). Fetal and placental weights did not differ between myoinositol/D-chiroinositol-treated and nontreated pregnant dams with metabolic-like syndrome and obesity.Conclusion: Combined inositol treatment during pregnancy improves blood pressure, glucose levels at the glucose tolerance test, and leptin levels in pregnant dams with metabolic-like syndrome phenotype but not in obese pregnant dams. In addition, inositol treatment was associated with lower gestational weight gain in the obese but not in the metabolic-like syndrome pregnant dams. [ABSTRACT FROM AUTHOR]

Background: Treatment of nonsevere hypertension during pregnancy is controversial. Sildenafil is a phosphodiesterase inhibitor that potentiates nitric oxide by promoting vasodilation. Nitric oxide plays a vital role in mediating the vascular adaptations during pregnancy.Objective: The objective of the study was to determine whether treatment with sildenafil during pregnancy would lower maternal systolic blood pressure without adversely affecting fetal growth.Study Design: Females with nonsevere hypertension (endothelial nitric oxide synthase(+/-)) were cross-bred with normotensive wild-type males. At gestational day 1, pregnant dams were randomized to either sildenafil (0.4 mg/mL per day, comparable dose used in human pregnancy) or water for 3 weeks. Four groups were then generated: wild type (n = 7), wild type-sildenafil (n = 11), endothelial nitric oxide synthase(+/-) (n = 8), and endothelial nitric oxide synthase(+/-)sildenafil (n = 7). On gestational day 18, systolic blood pressure was measured. Dams were killed, fetal and placental weights were obtained, and carotid arteries were dissected to measure in vitro vascular reactivity with a wire-myography system. Responses to phenylephrine, L-NG-nitroarginine methyl ester, acetylcholine, and sodium nitroprusside were studied.Results: Mean systolic blood pressure was elevated in the endothelial nitric oxide synthase(+/-) dams compared with wild-type controls (P = .03). Treatment with sildenafil decreased systolic blood pressure in the endothelial nitric oxide synthase(+/-)-treated dams compared with nontreated endothelial nitric oxide synthase(+/-) dams (P = .03). No differences were seen in the wild-type dams with or without sildenafil (P = .47). Fetuses from endothelial nitric oxide synthase(+/-) dams were smaller compared with wild-type controls (P < .001); however, when these endothelial nitric oxide synthase(+/-) dams were treated with sildenafil, fetal weight increased compared with the nontreated endothelial nitric oxide synthase(+/-) group (P < .001). No difference were seen in wild-type groups treated or not treated with sildenafil (P = .41). Placental weights were not significantly different among groups (endothelial nitric oxide synthase(+/-)sildenafil vs endothelial nitric oxide synthase(+/-) [P = .48]; wild-type-sildenafil vs wild type [P = .52]). Maximal vascular contraction induced by phenylephrine was blunted in endothelial nitric oxide synthase(+/-) dams treated with sildenafil compared with nontreated endothelial nitric oxide synthase(+/-) dams (P < .01). No change in contractile response was seen in wild-type groups treated or not treated (P = .53). When vessels were preincubated with L-NG-nitroarginine methyl ester, the contractile responses were similar among all groups (P = .54). In addition, maximal vascular relaxation induced by acetylcholine was improved in the endothelial nitric oxide synthase(+/-) dams treated with sildenafil compared with endothelial nitric oxide synthase(+/-) nontreated dams (P < .01). No change in relaxation response was seen in wild-type groups treated or not treated (P = .62). Sodium nitroprusside did not change the contractile response in any of the groups (P = .31).Conclusion: Pregnant dams deficient in endothelial nitric oxide synthase, a nonsevere hypertensive murine model, treated with sildenafil had lower maternal systolic blood pressure, increased fetal growth, and improvement in vascular reactivity. Treatment with sildenafil may be beneficial in pregnancies complicated by nonsevere hypertension. [ABSTRACT FROM AUTHOR]

Background: Uterine serous carcinoma is an aggressive form of endometrial cancer that carries an extremely poor prognosis. Solitomab is a novel bispecific single-chain antibody construct that targets epithelial cell adhesion molecule on tumor cells and also contains a CD3 binding region. We evaluated the expression levels of epithelial cell adhesion molecule and the in vitro activity of solitomab against primary uterine serous carcinoma cell lines in vitro and ex-vivo in the ascites of patients with uterine serous carcinoma.Objective: The purpose of this study was to determine the frequency of expression of epithelial cell adhesion molecule on uterine serous carcinoma cell lines and the ability of solitomab to modulate immune responses (T-cell proliferation, activation, cytokine production, and tumor killing) to tumor cells when it is combined with lymphocytes and epithelial cell adhesion molecule-positive cell lines or epithelial cell adhesion molecule-positive ascitic fluid in vitro.Study Design: Epithelial cell adhesion molecule expression was evaluated by flow cytometry in a total of 14 primary uterine serous carcinoma cell lines. Sensitivity to solitomab-dependent cellular-cytotoxicity was tested against a panel of primary uterine serous carcinoma cell lines that express different levels of epithelial cell adhesion molecule in standard 4-hour chromium release assays. The proliferative activity, activation, cytokine secretion (ie, type I vs type II), and cytotoxicity of solitomab in autologous tumor-associated T cells in the ascitic fluid of patients with uterine serous carcinoma was also evaluated by carboxyfluorescein succinimidyl ester and flow-cytometry assays. Differences in epithelial cell adhesion molecule expression, solitomab-dependent cellular-cytotoxicity levels were analyzed with the use of an unpaired t test. T-cell activation marker increase and cytokine release were analyzed by a paired t test.Results: Surface expression of epithelial cell adhesion molecule was found in 85.7% (12 of 14) of the uterine serous carcinoma cell lines that were tested by flow cytometry. Epithelial cell adhesion molecule-positive cell lines were found resistant to natural killer cells or T-cell-mediated killing after exposure to peripheral blood lymphocytes in 4-hour chromium-release assays (mean killing ± standard of the mean, 2.7% ± 3.1% after incubation of epithelial cell adhesion molecule-positive cell lines with control bispecific antibody construct). In contrast, after incubation with solitomab, epithelial cell adhesion molecule-positive uterine serous carcinoma cells became highly sensitive to T-cell cytotoxicity (mean killing, 25.7% ± 4.5%; P < .0001) by peripheral blood lymphocytes. Ex vivo incubation of autologous tumor-associated lymphocytes with epithelial cell adhesion molecule that expressed malignant cells in ascites with solitomab resulted in a significant increase in T-cell proliferation in both CD4+ and CD8+ T cells, increase in T-cell activation markers (ie, CD25 and HLA-DR), and a reduction in number of viable uterine serous carcinoma cells in ascites (P < .001).Conclusion: Solitomab induces robust immunologic responses in vitro that result in increased T-cell activation, proliferation, production of cytokines, and direct killing of tumor cells. These findings suggest that solitomab may represent a novel, potentially effective agent for the treatment of recurrent/metastatic and/or chemo-resistant uterine serous carcinoma-overexpressing epithelial cell adhesion molecule. [ABSTRACT FROM AUTHOR]

Abstract: A causative association was recently demonstrated between homozygous TREM2 mutations and frontotemporal dementia (FTD)-like syndrome and between heterozygous TREM2 exon2 genetic variations and late-onset Alzheimer's disease (AD). The objective of this study was to evaluate whether heterozygous TREM2 genetic variations might be associated to the risk of FTD. TREM2 exon 2 was sequenced in a group of 1030 subjects—namely, 352 patients fulfilling clinical criteria for FTD, 484 healthy control subjects (HCs), and 194 patients with AD. The mutation frequency and the associated clinical characteristics were analyzed. We identified 8 missense and nonsense mutations in TREM2 exon 2 in 24 subjects. These mutations were more frequent in patients with FTD than in HCs (4.0% vs. 1.0%, p = 0.005). In particular, TREM2 Q33X, R47H, T66M, and S116C mutations were found in FTD and were absent in HCs. These mutations were associated with either the semantic variant of primary progressive aphasia or the behavioral variant FTD phenotypes. The FTD and AD groups were not significantly different with regard to TREM2 genetic variation frequency (AD: 2.6%, p = 0.39). Heterozygous TREM2 mutations modulate the risk of FTD in addition to increasing susceptibility to AD. Additional studies are warranted to investigate the possible role of these mutations in the pathogenesis of neurodegenerative disorders. [Copyright &y& Elsevier]

Objective: The purpose of this study was to evaluate the association between unexplained stillbirth (SB) and single-nucleotide polymorphisms (SNPs) in genes involved in placental function using a well-characterized cohort. Study Design: Placentas were obtained from 50 unexplained SB and 46 live birth controls. Classification of stillbirth was by Wigglesworth criteria. SBs were stratified by weight: appropriate (AGA-SB) and small for gestational age (SGA-SB, less than the 10th percentile) and gestational age: before 32 and after 32 weeks. Placental DNA was extracted and various SNPs in the endothelial nitric oxide synthase (eNOS), Klotho, hypoxic inducible factor-1α, and and tumor necrosis factor-α genes were evaluated. Results: None of the SNPs were associated with SB overall. Significantly different genotype distribution emerged for eNOS-SNP rs1800783 when comparing AGA-SB with SGA-SB and control (P = .004). Its allele-A was more frequent in AGA-SB compared with both controls (P = .03) and SGA-SB (P = .001). No differences were seen accordingly to gestational age. Conclusion: Unexplained stillbirth in the setting of adequate growth is associated with carrier of allele A of rs1800783 eNOS gene in the placenta. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the intrauterine environment affects the postnatal vascular response to stress in a model of fetal programming induced by endothelial nitric oxide synthase deficiency. Study Design: Homozygous nitric oxide synthase knockout and wild-type controls were crossbred to obtain maternally and paternally derived heterozygous offspring. At 14 weeks of age, in vivo blood pressure measurements by telemetry, and in vitro carotid arteries vascular reactivity studies were performed in male offspring after subjecting them to shaker stress. Results: Maternally derived heterozygous offspring, compared with paternally derived heterozygous offspring, had significantly higher systolic blood pressure, mean arterial blood pressure, and pulse pressure before, as well as after introduction of the shaker stress. The difference in the latter between maternally and paternally derived heterozygous offspring was accentuated after stress. Maternally derived heterozygous offspring also had significantly higher contractile responses to phenylephrine when compared with paternally derived heterozygous offspring, and this was abolished after incubation with L-NAME. Conclusion: The adverse uterine environment affects the postnatal vascular response to stress. [Copyright &y& Elsevier]

In our continuing effort devoted at developing agents targeting the EphA2 receptor by means of protein-protein interaction (PPI) inhibitors, we report here the design and synthesis of a new class of l- β-homotryptophan conjugates of 3-β-hydroxy-Δ5-cholenic acid bearing a set of arylsulfonyl substituents at the indole nitrogen atom. An extensive structure-activity relationship (SAR) analysis indicates that the presence of a bulky lipophilic moiety at the indole nitrogen is fundamental for improving potency on the EphA2 receptor, while abrogating activity on the EphB1-EphB3 receptor subtypes. A rational exploration, guided by the combined application of an experimental design on σ p and π physicochemical descriptors and docking simulations, led to the discovery of UniPR1454, a 1-(4-(trifluoromethyl)phenyl)sulfonyl derivative acting as potent and competitive EphA2 antagonist able to inhibit ephrin-A1 dependent signals and to reduce proliferation of glioblastoma (U251) cell line at micromolar concentration. [Display omitted] • 1-(phenylsulfonyl)-1H-indole derivatives of l -β-homo-tryptophan conjugates were synthesized and tested in vitro. • New compounds acted as antagonists of the EphA2 receptor at μM concentration. • UniPR1454 displayed selectivity for the EphA subfamily of receptors. • UniPR1454 displayed significant antiproliferative activity on U251 GBM cell line. [ABSTRACT FROM AUTHOR]

Abstract: Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive neurodegenerative disorder characterized by cerebellar ataxia and oculomotor apraxia. The gene mutated in AOA2, SETX, encodes senataxin (SETX), a putative DNA/RNA helicase. The presence of the helicase domain led us to investigate whether SETX might play a role in DNA damage repair and telomere stability. We analyzed the response of AOA2 lymphocytes and lymphoblasts after treatment with camptothecin (CPT), mitomycin C (MMC), H2O2 and X-rays by cytogenetic and Q-FISH (quantitative-FISH) assays. The rate of chromosomal aberrations was normal in AOA2 cells after treatment with CPT, MMC, H2O2 and X-rays. Conversely, Q-FISH analysis showed constitutively reduced telomere length in AOA2 lymphocytes, compared to age-matched controls. Furthermore, CPT- or X-ray-induced telomere shortening was more marked in AOA2 than in control cells. The partial co-localization of SETX with telomeric DNA, demonstrated by combined immunofluorescence–Q-FISH and chromatin immunoprecipitation, suggests a possible involvement of SETX in telomere stability. [Copyright &y& Elsevier]

By-products of the fish industry can be a source of valuable molecules, with different technological applications. Fish bones contain both organic and inorganic phases (collagen/other proteins and calcium phosphate minerals respectively), with several uses and among them in cosmetics and medicine. Using the common extraction protocols, only one of the two phases can be extracted, while the other one is degraded. In the present work a method of extraction which allows the obtainment of both proteins and calcium phosphates was developed. Bones from two different species (salmon and sea bream) were tested. Saline solutions based on (NH 4)HCO 3 /(NH 4) 2 HPO 4 or (NH 4)HCO 3 were employed for the protein extraction. Analysis of the organic phase showed that the main extracted proteins were collagen in its different forms (especially α-1); some differences were observed between salmon and sea bream and between the methods of extraction. As for the mineral phase, after calcination at 700 °C, single phase hydroxyapatite was obtained with (NH 4)HCO 3 solution, while the use of (NH 4)HCO 3 /(NH 4) 2 HPO 4 led to a biphasic material of β-tricalcium phosphate and β-calcium pyrophosphate. Biocompatibility tests performed on both organic and inorganic extracts (with fibroblast and osteoblast-like cellular lines) showed their non-toxicity and, hence, their potential suitability for cosmetic or biomedical applications. This work shows that it is possible to obtain a more complete valorisation of the fish bones, with the simultaneous extraction of organic and inorganic valuable compounds. The principles of this process could be applied also to bones of other species, with a positive impact on the environment for the reduction of the wastes and a better use of all available resources. [Display omitted] • Innovative extraction process was developed for valorisation of fish bones. • Both organic (proteins) and inorganic (calcium phosphates) phases were extracted. • The process did not use toxic solvent but a saline aqueous solution. • The main component of the protein fraction was collagen, in its different forms. • Both proteins and calcium phosphates showed high biocompatibility. [ABSTRACT FROM AUTHOR]

Thermal stress is a factor that must be considered, particularly in working environments where severe microclimatic conditions can lead to a loss of well-being or, in the worst-case scenario, to worker health damage. When it comes to thermal comfort, the best conditions for ensuring worker activity, productivity, and well-being include not only the proper design of spaces and cooling/heating systems, but also constant, real-time monitoring of the worker's physical condition. This work aims to present a complete system comprising various components capable not only of ensuring the worker's thermal comfort through the use of innovative textiles for optimal heat exchange between the individual and the environment, but also of continuously monitoring certain physiological parameters useful in determining whether the worker is subject to thermal stress. The system developed also allows the worker to be warned in the event of thermal stress and provides control and analysis tools to safety operators. This work, in particular, provides ample space for the description and validation of the textile component, in addition to presenting the system architecture and describing the main components. Finally, the wireless sensors designed to monitor physiological parameters are described and validated, and a brief functional validation of some of the architecture's software components is presented. [ABSTRACT FROM AUTHOR]