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Objective and design: We aimed to identify cytokines whose concentrations are related to lung damage, radiomic features, and clinical outcomes in COVID-19 patients. Material or subjects: Two hundred twenty-six patients with SARS-CoV-2 infection and chest computed tomography (CT) images were enrolled. Methods: CCL18, CHI3L1/YKL-40, GAL3, ANG2, IP-10, IL-10, TNFα, IL-6, soluble gp130, soluble IL-6R were quantified in plasma samples using Luminex assays. The Mann–Whitney U test, the Kruskal–Wallis test, correlation and regression analyses were performed. Mediation analyses were used to investigate the possible causal relationships between cytokines, lung damage, and outcomes. AVIEW lung cancer screening software, pyradiomics, and XGBoost classifier were used for radiomic feature analyses. Results: CCL18, CHI3L1, and ANG2 systemic levels mainly reflected the extent of lung injury. Increased levels of every cytokine, but particularly of IL-6, were associated with the three outcomes: hospitalization, mechanical ventilation, and death. Soluble IL-6R showed a slight protective effect on death. The effect of age on COVID-19 outcomes was partially mediated by cytokine levels, while CT scores considerably mediated the effect of cytokine levels on outcomes. Radiomic-feature-based models confirmed the association between lung imaging characteristics and CCL18 and CHI3L1. Conclusion: Data suggest a causal link between cytokines (risk factor), lung damage (mediator), and COVID-19 outcomes. [ABSTRACT FROM AUTHOR]

Purpose: The local dimension of toxicity effect on humans and ecosystem from chemical emissions into rural environments is currently not considered in impact characterization models underlying the Life Cycle Assessment (LCA) methodology. The aim of the present study was to understand the relevance of considering a local exposure environment for the magnitude of damage related to human toxicity and ecotoxicity impacts associated with chemical emissions into a local environment. Method: Unit and realistic European emission scenarios were considered in a proposed multimedia nested box model, based on an existing framework modified with the inclusion of a local scale, and tested for ten chemicals in an illustrative case study. Results: A substantial damage increase in terms of characterization factors in the proposed model was found for human health, mainly for local freshwater emissions (up to three orders of magnitude compared to emissions into continental freshwater for naphthalene) and soil emissions (up to two orders of magnitude, in particular for emissions into natural soil for 1,2-dichloroethane). Conclusions: Based on our results, we suggest to use the proposed framework in LCA applications, when more specific information about the local emission environment is known. With respect to considering the local-scale, however, spatialized models might be preferable over nested box models to properly capture local phenomena in rather highly densely populated areas. [ABSTRACT FROM AUTHOR]

In manufacturing, Industry 4.0 operating models enable greener technologies. Thanks to digital technologies, environmental sustainability and organizational competitiveness are mutually reinforcing. The challenge for manufacturing organizations is to understand and quantify the magnitude of this synergistic action, and the holistic perspective of life cycle assessment tools may be a solution to the problem. Organizational Life Cycle Assessment (O-LCA) unlike Product Life Cycle Assessment (LCA) is still an under-researched methodology with few applications in manufacturing contexts. This paper aims to fill this gap by implementing and validating O-LCA in the case of an Italian ceramic tile manufacturer. Following the O-LCA guidelines and exploiting Industry 4.0 technologies to perform the inventory analysis, the environmental assessment was conducted in three different plants, comparing the sum of the partial impact results with the overall results scaled to the whole organization. The experimental results demonstrated the validity of the organizational approach as an appropriate methodological option to obtain relevant information on environmental performance that, being based on empirical evidence, better support decision-making processes. Furthermore, the study provides empirical evidence of how Industry 4.0 is an enabler not only for the adoption of greener technologies, but especially for facilitating the organizational environmental impact assessment that is the necessary condition in order to set up and maintain greener manufacturing contexts. [ABSTRACT FROM AUTHOR]

Doxorubicin (Dox) is one of the most commonly used anthracyclines for the treatment of solid and hematological tumors such as B−/T cell acute lymphoblastic leukemia (ALL). Dox compromises topoisomerase II enzyme functionality, thus inducing structural damages during DNA replication and causes direct damages intercalating into DNA double helix. Eukaryotic cells respond to DNA damages by activating the ATM-CHK2 and/or ATR-CHK1 pathway, whose function is to regulate cell cycle progression, to promote damage repair, and to control apoptosis. We evaluated the efficacy of a new drug schedule combining Dox and specific ATR (VE-821) or CHK1 (prexasertib, PX) inhibitors in the treatment of human B−/T cell precursor ALL cell lines and primary ALL leukemic cells. We found that ALL cell lines respond to Dox activating the G2/M cell cycle checkpoint. Exposure of Dox-pretreated ALL cell lines to VE-821 or PX enhanced Dox cytotoxic effect. This phenomenon was associated with the abrogation of the G2/M cell cycle checkpoint with changes in the expression pCDK1 and cyclin B1, and cell entry in mitosis, followed by the induction of apoptosis. Indeed, the inhibition of the G2/M checkpoint led to a significant increment of normal and aberrant mitotic cells, including those showing tripolar spindles, metaphases with lagging chromosomes, and massive chromosomes fragmentation. In conclusion, we found that the ATR-CHK1 pathway is involved in the response to Dox-induced DNA damages and we demonstrated that our new in vitro drug schedule that combines Dox followed by ATR/CHK1 inhibitors can increase Dox cytotoxicity against ALL cells, while using lower drug doses. • Doxorubicin activates the G2/M cell cycle checkpoint in acute lymphoblastic leukemia (ALL) cells. • ALL cells respond to doxorubicin-induced DNA damages by activating the ATR-CHK1 pathway. • The inhibition of the ATR-CHK1 pathway synergizes with doxorubicin in the induction of cytotoxicity in ALL cells. • The inhibition of ATR-CHK1 pathway induces aberrant chromosome segregation and mitotic spindle defects in doxorubicin-pretreated ALL cells. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Exploring the ATR-CHK1 pathway in the response of doxorubicin-induced DNA damages in acute lymphoblastic leukemia cells" published in the journal Cell Biology & Toxicology. The correction addresses an error in the funding section of the original article. The corrected statement clarifies the sources of funding for the study. The document also includes a note from the publisher, Springer Nature, stating their neutrality regarding jurisdictional claims and institutional affiliations. The authors of the article are listed at the end of the document. [Extracted from the article]

Introduction: Food inadequacies in the first 6 months of life are considered a global problem, with an emphasis on early complementary feeding introduction (CFI). This study aimed to identify the determinants of CFI. Methods: A birth cohort study (N = 641). Data on infant feeding was collected before 30 days, and at 2, 4, and 6 months of age and, at baseline, data regarding socioeconomic status, demographics, maternal and infant health, obstetric history, and infant care. The hypothesis was that the risk determinants for early CFI vary according to the type of food and the age range of this introduction. Twelve Cox regression models were fit with four outcomes (formula; other types of milk; other beverages; and solid/semi-solid foods) considering three different age ranges of the infant at their introduction (< 2 months, 2–4 months, and 4–6 months). Results: The introduction of the four food groups analyzed was early (median ages of introduction: formulas = 45 days; other milks = 135 days; other beverages = 120 days; solids and semi-solids = 135 days). The determinants that increased the risk of introducing formulas before 2 months were: primiparity, employed without maternity leave, mothers with unsatisfactory prenatal counseling and those who had cesarean sections. Not living with a partner, infant pacifier use at 2 months of age had a higher risk of introducing formula between 2 and 4 months of age. Non-white skin color, more than 35 years old, low maternal education, and lower family income increased the risk of introducing other types of milk between 2 and 4 months of age. Between 4 and 6 months of age, adolescent and low education level mothers had a higher risk of introducing other types of milk, unemployed was a protective factor against the introduction of other foods and beverages in this age group. Conclusions: The determinants of early CFI varied according to the type of food and the age of introduction. [ABSTRACT FROM AUTHOR]

Background: Monoallelic variants in the KIF1A gene are associated with a large set of clinical phenotypes including neurodevelopmental and neurodegenerative disorders, underpinned by a broad spectrum of central and peripheral nervous system involvement. Methods: In a multicenter study conducted in patients presenting spastic gait or complex neurodevelopmental disorders, we analyzed the clinical, genetic and neuroradiological features of 28 index cases harboring heterozygous variants in KIF1A. We conducted a literature systematic review with the aim to comparing our findings with previously reported KIF1A-related phenotypes. Results: Among 28 patients, we identified nine novel monoallelic variants, and one a copy number variation encompassing KIF1A. Mutations arose de novo in most patients and were prevalently located in the motor domain. Most patients presented features of a continuum ataxia-spasticity spectrum with only five cases showing a prevalently pure spastic phenotype and six presenting congenital ataxias. Seventeen mutations occurred in the motor domain of the Kinesin-1A protein, but location of mutation did not correlate with neurological and imaging presentations. When tested in 15 patients, muscle biopsy showed oxidative metabolism alterations (6 cases), impaired respiratory chain complexes II + III activity (3/6) and low CoQ10 levels (6/9). Ubiquinol supplementation (1gr/die) was used in 6 patients with subjective benefit. Conclusions: This study broadened our clinical, genetic, and neuroimaging knowledge of KIF1A-related disorders. Although highly heterogeneous, it seems that manifestations of ataxia-spasticity spectrum disorders seem to occur in most patients. Some patients also present secondary impairment of oxidative metabolism; in this subset, ubiquinol supplementation therapy might be appropriate. [ABSTRACT FROM AUTHOR]

Objective: The aims of this study were to develop a multiparametric prognostic model for death in COVID-19 patients and to assess the incremental value of CT disease extension over clinical parameters. Methods: Consecutive patients who presented to all five of the emergency rooms of the Reggio Emilia province between February 27 and March 23, 2020, for suspected COVID-19, underwent chest CT, and had a positive swab within 10 days were included in this retrospective study. Age, sex, comorbidities, days from symptom onset, and laboratory data were retrieved from institutional information systems. CT disease extension was visually graded as < 20%, 20–39%, 40–59%, or ≥ 60%. The association between clinical and CT variables with death was estimated with univariable and multivariable Cox proportional hazards models; model performance was assessed using k-fold cross-validation for the area under the ROC curve (cvAUC). Results: Of the 866 included patients (median age 59.8, women 39.2%), 93 (10.74%) died. Clinical variables significantly associated with death in multivariable model were age, male sex, HDL cholesterol, dementia, heart failure, vascular diseases, time from symptom onset, neutrophils, LDH, and oxygen saturation level. CT disease extension was also independently associated with death (HR = 7.56, 95% CI = 3.49; 16.38 for ≥ 60% extension). cvAUCs were 0.927 (bootstrap bias-corrected 95% CI = 0.899–0.947) for the clinical model and 0.936 (bootstrap bias-corrected 95% CI = 0.912–0.953) when adding CT extension. Conclusions: A prognostic model based on clinical variables is highly accurate in predicting death in COVID-19 patients. Adding CT disease extension to the model scarcely improves its accuracy. Key Points: • Early identification of COVID-19 patients at higher risk of disease progression and death is crucial; the role of CT scan in defining prognosis is unclear. • A clinical model based on age, sex, comorbidities, days from symptom onset, and laboratory results was highly accurate in predicting death in COVID-19 patients presenting to the emergency room. • Disease extension assessed with CT was independently associated with death when added to the model but did not produce a valuable increase in accuracy. [ABSTRACT FROM AUTHOR]

Background: Erenumab is a monoclonal antibody blocking the calcitonin gene–related peptide receptor, which has been approved for the preventive treatment of chronic migraine (CM). The aim of this study was to explore the safety and effectiveness of erenumab in patients suffering from CM and medication overuse headache (MOH) in a real-life setting, up to 1 year. Methods: Data regarding 81 patients treated with erenumab were retrospectively analyzed. Every 3 months, the following variables were collected: the mean number of headache days per month (headache index (HI)), the average number of painkillers taken per month (analgesic consumption (AC)), the mean number of days with painkiller consumption (number of days on medication (NDM)), the headache intensity (numeric rating scale (NRS) score), the 6-item Headache Impact Test (HIT-6), and the Self-Reported Instrument to Assess Work-Related Difficulties in Patients With Migraine (HEADWORK) scores. Results: The HI, AC, and NDM and the NRS, HIT-6, and HEADWORK scores were significantly lower at every time point from the 3rd month onward compared to baseline (all P < 0.0001). No significant differences were found between patients who underwent painkiller detoxification before starting erenumab and those who did not (all P > 0.05). No significant differences were found between patients taking erenumab in combination with other preventive treatments and the ones taking it alone (all P ≥ 0.05). Five patients dropped out because of adverse events, which resolved after stopping erenumab. Conclusion: Erenumab was safe and effective for CM complicated with MOH. Painkiller withdrawal and the association with other preventive treatment(s) seem useless. [ABSTRACT FROM AUTHOR]

Background: Neurosteroids affect the balance between neuroexcitation and neuroinhibition but have been little studied in migraine. We compared the serum levels of pregnenolone sulfate, pregnanolone and estradiol in women with menstrually-related migraine and controls and analysed if a correlation existed between the levels of the three hormones and history of migraine and age. Methods: Thirty women (mean age ± SD: 33.5 ± 7.1) with menstrually-related migraine (MM group) and 30 aged- matched controls (mean age ± SD: 30.9 ± 7.9) participated in the exploratory study. Pregnenolone sulfate and pregnanolone serum levels were analysed by liquid chromatography-tandem mass spectrometry, while estradiol levels by enzyme-linked immunosorbent assay. Results: Serum levels of pregnenolone sulfate and pregnanolone were significantly lower in the MM group than in controls (pregnenolone sulfate: P = 0.0328; pregnanolone: P = 0.0271, Student's t-test), while estradiol levels were similar. In MM group, pregnenolone sulfate serum levels were negatively correlated with history of migraine (R2 = 0.1369; P = 0.0482) and age (R2 = 0.2826, P = 0.0025) while pregnenolone sulfate levels were not age-related in the control group (R2 = 0.04436, P = 0.4337, linear regression analysis). Conclusion: Low levels of both pregnanolone, a positive allosteric modulator of the GABAA receptor, and pregnenolone sulfate, a positive allosteric modulator of the NMDA receptor, involved in memory and learning, could contribute either to headache pain or the cognitive dysfunctions reported in migraine patients. Overall, our results agree with the hypothesis that migraine is a disorder associated with a loss of neurohormonal integrity, thus supporting the therapeutic potential of restoring low neurosteroid levels in migraine treatment. [ABSTRACT FROM AUTHOR]

Background: Lynch syndrome (LS) is associated with germline mutations in one of the mismatch repair genes or EPCAM. The majority of the causative alterations are point mutations. Large genomic rearrangements represent only 5–20%. Hypothetically, the allelic imbalance, like the loss of heterozygosity, may be another high penetrance risk factor. Case presentation: We describe the case of a patient who developed 5 tumors during her lifetime and with a family history characterized by a high frequency of tumors associated with LS. The proband was tested for mutations and copy number alterations with a panel of hereditary cancer genes and by SNP array. She showed a 187 Kb duplication including EPCAM and the first 7 exons of MSH2, plus two loss of heterozygosity (LOHs) in chromosome 20 and one in chromosome X which include many tumor suppressor genes. Conclusion: We found a novel large EPCAM-MSH2 duplication associated with LS and the presence of LOHs in regions containing numerous tumor suppressors, raising the hypothesis that these alterations could contribute to cancer susceptibility. Our results underline the importance to deepen the knowledge of molecular mechanisms in order to determine the role in cancer predisposition of novel genetic alterations. [ABSTRACT FROM AUTHOR]

Alessandra Renieri and Anna Maria Pinto are members of the European Reference Network for rare malformation syndromes and rare intellectual and neurodevelopmental disorders, ERN-ITHACA. In the acknowledgment section author did not specify that some authors participate to a specific ERN related to the topic of the manuscript. Acknowledgement section should read as: B Acknowledgements b We thank Catherine J. Wrenn for expert editing of the manuscript and critical advice on tables and figures. [Extracted from the article]

Purpose: The restoration of cultural heritage, like in other production sectors, requires an innovative approach to integrate the principles of sustainability into processes. The main purpose of this article is to demonstrate that an integrated environmental and social impact assessment of restoration works can be conducted through the use of an operational model, which for the first time is applied to a real case of public private partnership (PPP) in the cultural heritage sector. Methods: The evaluation of the proposed strategy is carried out through an approach based on life cycle assessment (LCA) methodology, which takes into account environmental and social aspects. An environmental LCA analysis was conducted on a case study, assessing the effects of an intervention of a historical site that was restored to become a museum. The social effects arising from the intervention were then examined and evaluated with an approach based on the key points of the UNEP/SETAC S-LCA guidelines involving stakeholders, social topics, and performance indicators, thus defining a reference framework that can be adapted to the case study. Results and discussion: The environmental LCA analysis identified the phases of the restoration with the most impact as those related to the reconstruction of materials and elements that was necessary when the originals were too damaged to be recovered. The use and periodic replacement of electronic equipment in the museum also had a significant impact in the use phase of the buildings. The evaluation method for the social aspects scored each social theme, outlining the benefits produced by the restoration. The results show that the restoration had several positive effects, particularly in terms of social issues related to the local community. Conclusions: The environmental LCA assessed the advantages and the hotspots in the recovery and reuse of heritage buildings. The framework developed from the guidelines for the S-LCA of products is a suitable tool for the evaluation of social aspects related to cultural heritage interventions, after adapting the methodology of S-LCA to the context and to the reference case study. In some cases, evaluations are based on subjective judgments, but the results provide a reliable overview of the social impact generated. [ABSTRACT FROM AUTHOR]

Purpose: This research investigates the environmental performance of two products obtained using slag derived from copper primary production (copper slag, CS). The first is a tile produced as a traditional stoneware ceramic plate (CS tile) and the second product is a glass-ceramic sample obtained by melt quenching method (CS bulk sample). The products are intended for use in industrial plants as auxiliary heating elements aimed at absorbing microwave.Methods: The environmental assessment was carried out using LCA methodology, and the obtained outcomes were compared to the results calculated for a traditional tile containing silicon carbide (SiC tile).Results: The analyses show that the innovative products have an environmental load of 74% for the CS tile and 54% for the CS bulk sample lower than the environmental impact calculated for the traditional SiC-based material tile. The latter presents a high environmental load due to the incidence on the total impact of the raw materials production. In fact, LCA analysis proves that copper slag production has an impact of 96% lower with respect to the SiC production.Conclusions: This study identifies a possible waste reduction strategy in accordance with the European end-of-waste criteria, but these results should be supported by a site analysis in order to provide an appropriate context for decision making. [ABSTRACT FROM AUTHOR]

Background: Polypharmacy can appropriately treat multiple chronic conditions, but it can also increase potential harm. Polypharmacy information for primary headaches is minimal, despite drugs being the main tools to manage headaches.Objective: The aim was to evaluate the prevalence, characteristics and risk factors of polypharmacy in patients with primary headaches and examine whether these variables differ between episodic and chronic headache patients.Methods: We analysed polypharmacy (simultaneous use of five or more medications), medication type, comorbidity, and risk factors in 300 patients (mean age 42.81 ± 13.21 years) with primary headaches, divided into episodic and chronic, afferent to a headache centre.Results: Patients took an average of 4.37 medications. Polypharmacy was common in 40.7% of patients, and among chronic patients, it reached 58.8%. Most patients used medications (mainly nonsteroidal anti-inflammatory drugs; 73.5%) to treat acute headaches, and 30.4% of episodic and 64.7% of chronic sufferers underwent prophylactic treatment (P < 0.0001), mostly using antidepressants (77.3%). Up to 76.7% of the cohort was taking other medications, primarily for acid-related disorders (21.7%). Comorbidities were present in 59.7% of the cohort. Variables significantly associated with polypharmacy were comorbidities, prophylactic treatment, and triptans (P < 0.001).Conclusions: Patients with primary headaches, mainly young adults, are exposed to high polypharmacy, comparable to that of the elderly. Because increased numbers of drugs increase the risk of adverse reactions, the many medications concomitantly taken by primary headache sufferers should be frequently reviewed. [ABSTRACT FROM AUTHOR]

Silicate materials have been proposed as alternative cathodes for Li-ion battery applications. A novel mixture of silicates, labelled LiMnSi, based on the molar ratio among the Li/Mn/Si precursors, with promising electrochemical properties as positive electrode material is synthesized through a solid-state reaction. The results indicate the proposed synthetic method as effective for preparation of nanostructured silicate powders with average particle diameter of 30 nm. Structural morphology of the samples was determined using X-ray powder diffraction (XRPD), XPS and FESEM analysis. A joint analysis by XRPD data and by density functional theory (DFT) identified LiHMnSiO, LiMnSiO, LiSiO and LiMnSiO as components of LiMnSi mixture. The electrochemical performance of LiMnSi was evaluated by charge/discharge testing at constant current mode. LiMnSi discharge behaviour is characterized by high capacity value of 480 mA h g, although such capacity fades gradually on cycling. Ex situ XPS studies carried out on the electrode in both full charged and discharged states pointed out that LiSiO is decisive for achieving such high capacity. The discharge/charge plateau is most probably related to the change in the oxidation state of silicon at the surface of the silica material. [ABSTRACT FROM AUTHOR]

The results produced by the cluster and the supercell approaches, when applied to the study of the vacancy and $$\langle 100\rangle$$ split self-interstitial defects in diamond, are critically compared. The same computer code, Crystal, basis set and DFT functional (the hybrid B3LYP) are used. Clusters of increasing size (from 35 to 969 C atoms) are considered, and the results compared to those from a supercell containing $$128\pm 1$$ atoms, for which the interaction between defects in different cells can be considered negligible. It is shown that geometry and energy data (atomic relaxation, defect formation energy, relative energy between different spin states) show a very local nature and then converge rapidly with the cluster size. Other properties, frequently used for the characterization of the defects using relatively small clusters (band gaps, impurity energy levels in the gap, Raman spectra), converge slowly and, also at the limit of the very large clusters here considered, still differ from the periodic counterpart. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the potential of hair analysis to monitor medication adherence in headache patients undergoing chronic therapy. For this purpose, the following parameters were analyzed: the detection rate of 23 therapeutic drugs in headache patients' hair, the degree of agreement between the self-reported drug and the drug found in hair, and whether the levels found in hair reflected the drug intake reported by the patients. Methods: The study included 93 patients suffering from primary headaches declaring their daily intake of at least one of the following drugs during the 3 months before the hair sampling: alprazolam, amitriptyline, citalopram, clomipramine, clonazepam, delorazepam, diazepam, duloxetine, fluoxetine, flurazepam, levomepromazine, levosulpiride, lorazepam, lormetazepam, mirtazapine, paroxetine, quetiapine, sertraline, topiramate, trazodone, triazolam, venlafaxine, and zolpidem. A detailed pharmacological history and a sample of hair were collected for each patient. Hair samples were analyzed by liquid chromatography-electrospray tandem mass spectrometry, using a previously developed method. Results: All 23 drugs were detected in the examined hair samples. The agreement between the self-reported drug and the drug found in hair was excellent for most analytes ( P < 0.001, Cohen's kappa); a statistically significant relationship ( P < 0.05, linear regression analysis) between dose and hair level was found for amitriptyline, citalopram, delorazepam, duloxetine, lorazepam, and venlafaxine. Conclusions: Hair analysis proved to be a unique matrix to document chronic drug use in headache patients, and the level found for each individual drug can represent a reliable marker of adherence to pharmacological treatments. [ABSTRACT FROM AUTHOR]

Purpose: The increasing use of engineered nanomaterials (ENMs) in industrial applications and consumer products is leading to an inevitable release of these materials into the environment. This makes it necessary to assess the potential risks that these new materials pose to human health and the environment. Life cycle assessment (LCA) methodology has been recognized as a key tool for assessing the environmental performance of nanoproducts. Until now, the impacts of ENMs could not be included in LCA studies due to a lack of characterization factors (CFs). This paper provides a methodological framework for identifying human health CFs for ENMs. Methods: The USEtox™ model was used to identify CFs for assessing the potential carcinogenic and non-carcinogenic effects on human health caused by ENM emissions in both indoor (occupational settings) and outdoor environments. Nano-titanium dioxide (nano-TiO) was selected for defining the CFs in this study, as it is one of the most commonly used ENMs. For the carcinogenic effect assessment, a conservative approach was adopted; indeed, a critical dose estimate for pulmonary inflammation was assumed. Results and discussion: We propose CFs for nano-TiO from 5.5E−09 to 1.43E−02 cases/kg for both indoor and outdoor environments and for carcinogenic and non-carcinogenic effects. Conclusions: These human health CFs for nano-TiO are an important step toward the comprehensive application of LCA methodology in the field of nanomaterial technology. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to evaluate the detection rate of almotriptan, eletriptan, frovatriptan, sumatriptan, rizatriptan, and zolmitriptan in the hair of migraineurs taking these drugs; the degree of agreement between type of self-reported triptan and triptan found in hair; if the concentrations in hair were related to the reported cumulative doses of triptans; and whether hair analysis was able to distinguish occasional use from the overuse of these drugs. Methods: Out of 300 headache patients consecutively enrolled, we included 147 migraine patients who reported to have taken at least one dose of one triptan in the previous 3 months; 51 % of the patients overused triptans. A detailed pharmacological history and a sample of hair were collected for each patient. Hair samples were analyzed by liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) by a method that we developed. Results: All the triptans could be detected in the hair of the patients. The agreement between type of self-reported triptan and type of triptan found in hair was from fair to good for frovatriptan and zolmitriptan and excellent for almotriptan, eletriptan, sumatriptan, and rizatriptan ( P < 0.01, Cohen's kappa). The correlation between the reported quantities of triptan and hair concentrations was statistically significant for almotriptan, eletriptan, rizatriptan, and sumatriptan ( P < 0.01, Spearman's rank correlation coefficient). The accuracy of hair analysis in distinguishing occasionally users from overusers was high for almotriptan (ROC AUC = 0.9092), eletriptan (ROC AUC = 0.8721), rizatriptan (ROC AUC = 0.9724), and sumatriptan (ROC AUC = 0.9583). Conclusions: Hair analysis can be a valuable system to discriminate occasional use from triptan overuse. [ABSTRACT FROM AUTHOR]

Most complex decisions involve several stakeholders and therefore need to be solved using a group multi-criteria decision method. However, stakeholders or decision-makers often have divergent views, especially in the environmental sector. In order to integrate this divergence, a new group fuzzy PROMETHEE approach is introduced to combine the traditional environmental criteria of life cycle assessments with social and economic criteria. The modelling of uncertainty within the group of decision-makers using a fuzzy approach makes this method unique. The proposed fuzzy approach differs significantly from the standard one. The decision-makers express their judgments in crisp forms. In order to take into account the intrinsic dispersion of judgments within the group, a posteriori fuzzification procedure is applied. The crisp values are not simply aggregated; they are converted into a triangular fuzzy number based on the given evaluations. As a consequence, the definition of fuzzy membership functions, as required in standard fuzzy logic, is not required, which simplifies the process and makes it more reliable. The new approach is illustrated with a real case study concerning the selection of the best waste treatment solution in a natural park from among a traditional incinerator and an innovative integrated plant. [ABSTRACT FROM AUTHOR]

Interictal electroencephalogram (EEG) abnormalities are frequently associated with autism spectrum disorders (ASD), although their relationship with the clinical features of ASD, particularly the regressive onset, remains controversial. The aim of this study was to investigate whether the characteristics of interictal EEG abnormalities might help to distinguish and predict definite phenotypes within the heterogeneity of ASD. We reviewed the awake and sleep interictal EEGs of 220 individuals with idiopathic ASD, either with or without a history of seizures. EEG findings were analyzed with respect to a set of clinical variables to explore significant associations. A brain morphometry study was also carried out on a subgroup of patients. EEG abnormalities were seen in 154/220 individuals (70 %) and were mostly focal ( p < 0.01) with an anterior localization ( p < 0.001). They were detected more frequently during sleep ( p < 0.01), and were associated with a regressive onset of ASD ( p < 0.05), particularly in individuals with focal temporal localization ( p < 0.05). This association was also stronger in regressive patients with concurrent macrocephaly, together with a relative volumetric reduction of the right temporal cortex ( p < 0.05). Indeed, concurrence of temporal EEG abnormalities, regression and macrocephaly might possibly define a distinct endophenotype of ASD. EEG-based endophenotypes could be useful to untangle the complexity of ASD, helping to establish anatomic or pathophysiologic subtypes of the disorder. [ABSTRACT FROM AUTHOR]

Fine needles of mullite grains were obtained successfully in a compact and low porous matrix using solid state sintering. We treated high-grade kaolin and sand-rich kaolin at 750 °C to amorphous metakaolins, and bauxite at 1,000 °C to metastable alumina. By designing a stochiometric composition of mullite, each amorphous metakaolin was added to metastable alumina. Fine grains of mullite with almost complete crystallization were obtained from 1,350 °C in a case of amorphous metakaolin from high-grade kaolin and at 1,550 °C in the other case where amorphous metakaolin is from sand-rich kaolin. The difference in the temperatures of mullitization was linked to the late dissolution of silica from the cristobalite and quartz phases which were still present in the sand-rich metakaolin sample at 1,350 °C. The use of metastable alumina and metakaolin instead of kaolin to design the mullite matrix allows the increase in number of mullite nucleation sites. This results to high densification and crystallization, fine grain size, and high mechanical properties of the final matrix. [ABSTRACT FROM AUTHOR]

Purpose: Ceramic tiles play a strategic role in the Italian market; currently, the Italian production is of 367.2 million m (Confindustria Ceramica ). In 2009, Italy was positioned as the world's fourth largest producer of ceramic tiles, producing 368 million m of the world's total production of 1,735 million m Giacomini (Ceram World Rev 88:52-68, ). Therefore, there is an ongoing effort to create innovations in the products offered and their manufacturing processes, in order to better compete on the market and to create eco-friendly products. Recently, the Italian Ceramic District has increased its focus on environmental issues with the aim of protecting natural resources and reducing the energy and material consumption. For this reason, a new product was born in the Italian Ceramic District, namely, a large thin ceramic tile (dimensions 1,000 mm × 3,000 mm × 3.5 mm) reinforced with a fibreglass backing, which gives the product excellent resistance and flexibility properties. The aim was to manufacture a new product with lower environmental impact than the traditional one. The production of a large thin ceramic tile requires, in fact, a lower quantity of materials, transports and energy consumptions comparing to the same metres square of traditional ceramic tile. At the present, no comparative life cycle assessment (LCA) studies have been performed between traditional and innovative ceramic stoneware tiles. This study analyses, for the first time, a life cycle of the innovative ceramic product (porcelain stoneware) developed by a company of the Italian Ceramic District. Methods: The analysis is performed using the LCA methodology, in order to identify environmental impacts, energy consumption and CO equivalent emissions that occur during extraction of raw materials, transportation, production, material handling, distribution and end-of-life stages within a cradle to grave perspective. Results and conclusions: LCA analysis indicates that the highest environmental impact mainly affects the respiratory inorganics impact category due to base slip production (27.62 %), caused by the transport of the raw materials and by non-renewable impact category due to both the pasting phase (21.31 %) and the two-component adhesive manufacture. The major greenhouse gas (GHG) emissions are related to the production of polyurethane, a component of the adhesive used in the pasting stage, and to the natural gas consumption in the firing process. [ABSTRACT FROM AUTHOR]

Neutron total cross sections of Au and Ta have been measured at the nELBE photoneutron source in the energy range 0.1-10MeV with a statistical uncertainty of up to 2% and a total systematic uncertainty of 1%. This facility is optimized for the fast neutron energy range and combines an excellent time structure of the neutron pulses (electron bunch width 5ps) with a short flight path of 7m. Because of the low instantaneous neutron flux transmission measurements of neutron total cross sections are possible, that exhibit very different beam and background conditions than found at other neutron sources. [ABSTRACT FROM AUTHOR]

The attenuated vaccinia virus, modified vaccinia Ankara, has been engineered to deliver the tumor antigen 5T4 (TroVax). Here, we report results from a randomized open-label phase II trial in castration-resistant prostate cancer patients in which TroVax was administered in combination with docetaxel and compared against docetaxel alone. The aim was to recruit 80 patients (40 per arm), but the study was terminated early due to recruitment challenges. Therefore, this paper reports the comparative safety and immunological and clinical efficacy in 25 patients, 12 of whom were treated with TroVax plus docetaxel and 13 with docetaxel alone. 5T4-specific immune responses were monitored throughout the study. Clinical responses were assessed by measuring changes in tumor burden by CT and bone scan and by quantifying PSA concentrations. TroVax was well tolerated in all patients. Of 10 immunologically evaluable patients, 6 mounted 5T4-specific antibody responses. Patients treated with TroVax plus docetaxel showed a greater median progression-free survival of 9.67 months compared with 5.10 months for patients on the docetaxel alone arm ( P = 0.097; HR = 0.31; 95 % CI 0.08-1.24). Importantly, a pre-treatment biomarker previously demonstrated to predict 5T4 immune response and treatment benefit showed a strong association with 5T4 antibody response and a statistically significant association with progression-free survival in patients treated with TroVax plus docetaxel, but not docetaxel alone. [ABSTRACT FROM AUTHOR]

Background: The majority of patients suffering from cluster headache (CH) are smokers and it has been suggested that smoking may trigger the development of CH. The aim of this pilot survey was to describe: 1. the differences between current, former, and never smokers CH patients; 2. if smoking changed during an active cluster period; 3. if CH changed after quitting. Methods: All outpatients with episodic CH according to the criteria of ICHD-II who were consecutively seen for the first time from October 2010 to April 2012 at a headache centre were interviewed by phone using a specifically prepared questionnaire. Statistical differences between continuous variables were analysed by the Student’s t-test or the one-way analysis of variance (ANOVA), followed by Newman-Keuls post-hoc testing. Comparisons between percentages were made using the Chi-square test or Fisher’s exact test. All data were expressed as the mean ± standard deviation (SD). Results: Among a total of 200 patients surveyed (172 males, 28 females; mean age ± SD: 48.41 ± 12 years) there were 60%, 21%, and 19% of current, former, and never smokers, respectively. Current smokers reported longer active periods (12.38 ± 10 weeks) and a higher maximum number of attacks per day (3.38 ± 1) compared to never smoker CH patients (5.68 ± 4 weeks, P <0.05 and 2.47 ± 1, P <0.05, respectively). During the active period most of the patients stated to decrease (45.7%) or not to change (45.7%) the number of cigarettes smoked. Among those who decreased smoking, most (83.8%) reported that they had less desire to smoke. After quitting, the majority of former smokers stated that their headache had not changed. Conclusions: Patients with episodic CH who are also smokers appear to have a more severe form of the disorder. However, it is unlikely that between CH and smoking there is a causal relationship, as CH patients rarely improve quitting smoking. [ABSTRACT FROM AUTHOR]

Medication overuse headache (MOH) is a severe burden to sufferers and its treatment has few evidence-based indications. The aim of this study is to evaluate efficacy and safety of nabilone in reducing pain and frequency of headache, the number of analgesic intake and in increasing the quality of life on patients with long-standing intractable MOH. Thirty MOH patients were enrolled at the University of Modena's Interdepartmental Centre for Research on Headache and Drug Abuse (Italy) in a randomized, double-blind, active-controlled, crossover study comparing nabilone 0.5 mg/day and ibuprofen 400 mg. The patients received each treatment orally for 8 weeks (before nabilone and then ibuprofen or vice versa), with 1 week wash-out between them. Randomization and allocation (ratio 1:1) were carried out by an independent pharmacy through a central computer system. Participants, care givers, and those assessing the outcomes were blinded to treatment sequence. Twenty-six subjects completed the study. Improvements from baseline were observed with both treatments. However, nabilone was more effective than ibuprofen in reducing pain intensity and daily analgesic intake ( p < 0.05); moreover, nabilone was the only drug able to reduce the level of medication dependence (−41 %, p < 0.01) and to improve the quality of life ( p < 0.05). Side effects were uncommon, mild and disappeared when nabilone was discontinued. This is the first randomized controlled trial demonstrating the benefits of nabilone on headache, analgesic consumption and the quality of life in patients with intractable MOH. This drug also appears to be safe and well-tolerated. Larger scale studies are needed to confirm these preliminary findings. [ABSTRACT FROM AUTHOR]

During the last decade a tremendous technologic progress based on genome-wide profiling of genetic aberrations, structural DNA alterations, and sequence variations has allowed a better understanding of the molecular basis of pediatric and adult B/T- acute lymphoblastic leukemia (ALL), contributing to a better recognition of the biological heterogeneity of ALL and to a more precise definition of risk factors. Importantly, these advances identified novel potential targets for therapeutic intervention. This review will be focused on the cytogenetic/molecular advances in pediatric and adult ALL based on recently published articles. [ABSTRACT FROM AUTHOR]

Purpose: Pulp and paper manufacturing constitutes one of the largest industry segments in term of water and energy usage and total discharges to the environment. More than many other industries, however, this industry plays a key role in sustainable development because its most important raw material, wood fiber, is renewable Dias and Houtman (Environ Prog 23(4):347-357, ). Actually, even if the communication is dominated by electronic media, paper-based communication has a role to play due to its unique practical and aesthetic qualities. This research aims to assess the environmental impact of advertising folders produced with different papers and distributed by a system of Italian consumers' cooperatives in order to indicate the possible options of improvement and to assess the CO emitted during the entire life cycle. Methods: Life cycle assessment (LCA) was performed from cradle-to-grave considering paper production, transport from paper mill to printing site, printing, distribution, and disposal. Data for the study were directly collected from specific companies and completed on the basis of literature information. The analysis was conducted using the SimaPro 7.1.5 software and IMPACT 2002+ method to assess all its environmental impact and damage categories. Results and discussion: LCA analysis indicates that the higher environmental impact is mainly due to paper production and printing processes. The main operations which generate the major impact in the paper production stage are related to the direct or indirect fossil energy use, the production of additives for bleaching operations, and the collection and selection of waste paper. Printing causes relevant impacts for the electricity and ink production and for the aluminum plates used in the offset printing. Moreover, the use of paper with low quantity of additives and small amount of primary fibers causes a reduction of the environmental load of 13.94 %. The major global warming potential value was found for advertising folders made with little amount of mechanical pulp which slightly contributes to the absorption of CO. Conclusions: The analysis pointed out the relevance of the paper production phase and of the printing step within the advertising folders life cycle and allowed to detect the other critical stages of the life cycle. Paper composition greatly affects the environmental impact of the advertising folders' life cycle. [ABSTRACT FROM AUTHOR]

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105-190 (). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze cutaneous pain threshold (CPT) during the interictal phase in headache patients, and the relationships between headache frequency and analgesic use. A consecutive series of 98 headache patients and 26 sex- and age-balanced controls were evaluated. Acute allodynia (AA) was assessed by Jakubowski questionnaire, and interictal allodynia (IA) by a skin test with calibrated monofilaments. AA is widely known as a symptom more present in migraine than in TTH spectrum: in our study this was confirmed only in cases of episodic attacks. When headache index rises towards chronicization, the prevalence of AA increases in both headache spectrums ( χ 13.55; p < 0.01). AA was associated with IA only in cases of chronic headache. When headache becomes chronic, mostly in presence of medication overuse, interictal CPT decreases and IA prevalence increases ( χ 20.44; p < 0.01), with closer association than AA. In MOH patients there were no significant differences depending on the diagnosis of starting headache (migraine or tension type headache) and, in both groups, we found the overuse of analgesics plays an important role: intake of more than one daily drug dramatically reduces the CPT ( p < 0.05). Thus, when acute allodynia increases frequency, worsens or appears for the first time in patients with a long-standing history of chronic headache, it could reasonably suggest that the reduction of CPT had started, without using a specific practical skin test but simply by questioning clinical headache history. In conclusion, these results indicate that the role of medication overuse is more important than chronicization in lowering CPT, and suggest that prolonged periods of medication overuse can interfere with pain perception by a reduction of the pain threshold that facilitates the onset of every new attack leading to chronicization. [ABSTRACT FROM AUTHOR]

Triptans, selective 5-HT1B/1D receptor agonists, are specific drugs for the acute treatment of migraine that have the same mechanism of action. Here, it is discussed why the differences among kinetic parameters of oral triptans have proved not to be very important in clinical practice. There are three main reasons: (1) the differences among the kinetic parameters of oral triptans are smaller than what appears from their average values; (2) there is a large inter-subject, gender-dependent, and intra-subject (outside/during the attack) variability of kinetic parameters related to the rate and extent of absorption, i.e., those which are considered as critical for the response; (3) no dose-concentration-response curves have been defined and it is, therefore, impossible both to compare the kinetics of triptans, and to verify the objective importance of kinetic differences; (4) the importance of kinetic differences is outweighed by non-kinetic factors of variability of response to triptans. If no oral formulations are found that can allow more predictable pharmacokinetics, the same problems will probably also arise with new classes of drugs for the acute treatment of migraine. [ABSTRACT FROM AUTHOR]

There are a large number of drugs inducing headache as an adverse reaction. Nevertheless, headaches as adverse reactions to drugs have received limited attention. Non-serious adverse reactions, such as headache, are not quantified and described as accurately as serious, life threatening ones. However, non-serious reactions can also be extremely troublesome, above all when they are chronic: they can affect patients’ quality of life and contribute to non-compliance. It is absolutely possible that the number of patients with headache as an adverse reaction, which is going to increase, considering the growing use of medications. Physicians should, therefore, be aware of this issue. Indeed, it is difficult to attribute the diagnosis of adverse drug reaction to a condition, headache, which is also a very common symptom in general population. [ABSTRACT FROM AUTHOR]

The marketing of sumatriptan, a selective serotonin (5-HT) 1B/1D agonist, first of the class of triptans, has increased the therapeutic options for the treatment of migraine attacks. However, almost one third of patients in clinical trials fail to have headache relief after oral administration of sumatriptan. To evaluate whether the interindividual differences in the clinical response following oral administration of sumatriptan are due to differences in its pharmacokinetics. We compared the pharmacokinetics of sumatriptan after oral (100 mg) and subcutaneous (6 mg) administration in two age- and gender-matched groups: ten subjects (group A) with satisfactory response and ten (group B) with unsatisfactory response to oral sumatriptan. Patients were studied during headache-free intervals. Blood samples were taken serially from baseline to 360 min after oral administration and from baseline to 180 min after subcutaneous injection. Sumatriptan plasma concentrations were determined by high-performance liquid chromatography (HPLC) with an electrochemical detector. Following oral dosing, patients of group A absorbed sumatriptan significantly faster and achieved early plasma levels significantly higher than patients of group B. The systemic exposure to sumatriptan during the first 2 h, which are the most important for rapid onset of action and for antimigraine efficacy, was significantly greater in group A than in group B ( P < 0.001, Student’s t test for independent data). On the other hand, after subcutaneous injection of sumatriptan, the profile of the curves was similar in all patients, and there were no differences in pharmacokinetics between group A and group B. The slow rate and low extent of absorption of the drug during the first 2 h after dosing observed in patients of group B could explain their unsatisfactory response to oral sumatriptan. [ABSTRACT FROM AUTHOR]

Background, Aims and Scope. The interest in recycling materials at the end of their life is growing in the industry in general. As regards the Wastes of Electrical and Electronic Equipment (WEEE), an appreciable increase of these materials has been noticed in the last decades, 117 103 tons of WEEE have been produced in Italy in 2002 according to Ecohitech [11 and the increase in this kind of waste is three times higher than that of the municipal waste according to the FISE ASSOAMBIENTE report [21. Within WEEE, End-of-Life Cathode Ray Tube (EOL CRT) glass, the main part of TV sets and PC monitors, is here analysed using both a technical approach to establish a possible reuse of the glass in a open- loop recycling field (ceramic industry) and a methodology (LCA) capable of providing environmental evaluations. Methods. The technological characterization was performed by chemical resistance tests (UNI EN ISO 10545–13), staining tests (UNI EN ISO 10545–14) with blue methylene and potassium permanganate (KMnO4), and surface abrasion tests (UNI EN ISO 10545–7). The LCA study was conducted using the SimaPro 5.0 software and Eco-Indicator 99 as an evaluation method. Results and Discussion. The good technical results, reached by using cleaned EOL CRT panel glass inside a ceramic glaze formulation instead of a commercial frit, are supported by the environmental impact evaluation, which shows a decrease of the overall potential damage (measured in Points) of 36% and, in particular, a reduction of 53% in `Human health', 31% in `Ecosystem quality' and 24% in Resources'. Conclusions. This study has demonstrated that this new, open- loop recycling strategy for the CRT glass significantly reduces the environmental impact of the ceramic glaze production process. In fact, in all damage categories examined in this study, there is a minor impact. An improvement is evident in the respiratory inorganics sub-category related to the lowering of dusts mainly and to a lesser amount with NOx and SOx in the climate change sub-category, due mainly to the reduction of CO2 emission correlated to the avoided combustion of the mixture which feeds melting furnaces in the frit production. Thus, the damage decrease in `Ecosystem quality' is prevalently due to the lower NOx emissions by the kilns in the frit production that is evident in the acidificationleutrophication sub-category. Finally, the significant saving in the ‘Resource’ category is principally linked to the fossil fuels sub-category, thanks to the niethane saving which stokes the melting furnaces. Perspectives. Furthermore, the decrease in CO2 emission (94.4%) evident in the climate change sub-category is a very important topic because it is in line with the Kyoto protocol (1997), where significant efforts have been exerted for the reduction of the green house gases emission, notably CO2. The CO2 emission is correlated to the combustion of the mixture which feeds melting kilns in the frit production, therefore the recycling of secondary raw materials, already in a glass state, can reduce the emissions of this gas. This reduction can be termed as environmental credit and it is an ex- ample of an allocation of environmental loads in a open-loop recycling, where waste from one industrial system are used as raw materials in another product system. [ABSTRACT FROM AUTHOR]

Objective: To assess the clinical impact of ad- verse reactions related to drugs for primary headache treatment. Methods: We examined the adverse reactions to 360 medications prescribed by the specialists of the Head- ache Centre of the University of Modena and Reggio Emilia to 256 consecutive outpatients (214 female, 42 male; mean age: 38.88 ± 14.06 years; range 10-72 years). Adverse reactions were reported by patients during scheduled follow-up visits, classified by specialists and reassessed by a clinical pharmacologist. Results: Adverse reactions with a causal relationship classified as definite/probable/possible were 202 (56%): 62% (80/129) were due to acute treatments and 53% (122/231) to prophylactic treatments (χ² test, P = 0.115 ns). More than 90% of the adverse reactions were of limited intensity [mild (58%) or moderate (36%)]. Only 5% were severe, and two reactions (1%) were serious. The most affected apparatus was the nervous system (41%). Of these adverse reactions, 43% caused the discontinuance of the treatment, especially of prophylaxis (54%). Patients evaluated 70% of the medications as effective, but, at the same time, they considered most of the adverse reactions (69%) unacceptable. Conclusion: Adverse reactions related to headache medications have a strong impact on patients' management, even if their real intensity and severity are usually very limited. Drugs for headache treatment are still far from being ideal drugs. To prevent the discontinuance of effective medications, the physician, prior to prescribing, should assess, together with the patient, the acceptability of the more common adverse drug reactions. [ABSTRACT FROM AUTHOR]

Androgen receptor (AR) overexpression is one of the characteristics of prostate cancer (PC) that progresses to hormone independence. An androgen-independent (AI) derivative, with much higher AR-mRNA and protein levels than the parental LNCaP cell line, whose proliferation was androgen dependent (AD), was used to explore the mechanism of AR overexpression. We found that a suppressor element (ARS), previously identified in mouse AR and located in the 5'-untranslated region of human AR gene, malfunctions in AI cells. Transfection of constructs that included ARS element into AD cells reduced the transactivating activities of both AR promoter and a heterologous SV40 promoter. The deletion of ARS resulted in an eightfold increase in AR-promoter activity in AD cells, but had no effect in AI cells. Moreover, the nuclear extracts of AD cells contained proteins that produced a specific, ARS-binding complex, while this complex appeared to have been lost from AI cells. Most importantly, treatment of AI cells with a demethylating agent or histone deacetylase inhibitors restored the lost ARS-binding complex. The restoration of the complex coincided with a reduced expression of AR-mRNA and protein and a reduced rate of AR-gene transcription, determined by nuclear run-on experiment. Thus, epigenetic transcriptional silencing of the suppressor protein(s) may be responsible for AR overexpression in AI cells, and its reversal in hormone-independent PC may normalize AR levels and restore their hormone dependence.Oncogene (2004) 23, 5175-5184. doi:10.1038/sj.onc.1207654 Published online 24 May 2004 [ABSTRACT FROM AUTHOR]

The main goals of prophylactic treatment for migraine are to decrease headache attack frequency, length and intensity, to improve the efficacy of symptomatic drugs, to reduce their need, and to prevent pain chronicization. Therefore, the choice of a prophylactic drug and the modality of treatment is not easy and often not adequately supported by literature data nor by current national and international guidelines. Moreover, the response of the migraine patient to treatment is often unforeseeable. The aim of this short review is to provide some practical suggestions to the physician regarding how to decide when to begin a migraine prophylactic treatment and how to apply the specific guidelines of the Italian Society for the Study of Headache. [ABSTRACT FROM AUTHOR]

Sumatriptan is a selective agonist of 5HT1 (1B/1D) receptors, which has proved to be effective and safe for the acute treatment of migraine attacks. Nevertheless, its use by migraine sufferers is still limited and some patients consider adverse reactions related to sumatriptan, especially chest symptoms, unacceptable even if not serious. Moreover, in clinical trials, almost one third and one sixth of patients, respectively, fail to experience headache relief either after oral or after subcutaneous sumatriptan administration. Our aim was to verify whether differencies in sumatriptan pharmacokinetics could explain non–response and/or adverse drug reactions. Sumatriptan levels were determined by HPLC with electrochemical detection. Pharmacokinetic parameters were calculated using a computer program (PK Solutions 2.0; non compartmental Pharmacokinetics Data Analysis). After oral administration, sumatriptan is rapidly absorbed and sometimes displays multiple peaks of plasma concentration. This “multiple peaking” gives rise to considerable inter–subject variability in the time of reaching maximum plasma concentration. Pharmacokinetic parameters of sumatriptan, both after oral and subcutaneous administration, were similar in the three patient groups. Blood pressure and heart rate did not show any significant differences between groups. Pharmacokinetic parameters and bioavailability of sumatriptan did not seem to be correlated either to the lack of efficacy or the appearance of side effects. These results could depend on the limited number of patients studied. [ABSTRACT FROM AUTHOR]

The calculation of the full vibrational spectrum (Infrared or Raman) of very large systems (say larger than one thousand atoms) is not only very expensive, but also of relatively low interest, as in many (most of the) cases only a subset of modes, well separated from the large, diffuse bands resulting from the superposition of thousands of peaks, is used for the spectroscopic characterization of the specific system under study. Here, a fragment strategy, consisting in computing and diagonalizing a reduced (in size) Hessian matrix centered around the zone of interest, is illustrated, and its accuracy and efficiency documented, by comparison with the full Hessian diagonalization (FHD) scheme. Three test cases are considered, showing different vibrational features. They are defects in diamond: the VN3H defect (V stands for the vacancy), where the interesting point is the characterization of the bending and stretching modes of H, well separated from the large band resulting from the perturbation of the diamond manifold; the VH4 defect (four H atoms in the vacancy, with vibrational modes related to H appearing both at high and low wave numbers); and the I2N interstitial defect, with modes in which the N atoms are involved, appearing at wave numbers not far from the manifold of the perfect diamond modes. So the three cases, apparently similar, explore three different situations of interest for the fragment strategy: (1) localized modes very well separated from the large diamond continuous band (VN3H); (2) modes at upper border of the large diamond continuous band (I2N): a case in which the modes of interest appear both as separated from and merged with the large continuous band (VH4). It turns out that in all cases relatively small fragments, containing from 2 to 40 atoms, permit to reproduce with high accuracy (the difference with respect to the FHD being always smaller than 5 cm-1 for the wave numbers, and a few percent for the IR intensity) the spectral feature(s) of interest, at a computational cost that is only a small fraction of the one required by the FHD. [ABSTRACT FROM AUTHOR]

Neutron total cross sections of natFe, 197Au and natW have been measured at the n ELBE neutron time-of-flight facility in the energy range 0.15-8MeV with an uncertainty due to counting statistics of up to 2% and a total uncertainty due to systematic effects of 1%. The neutrons are produced with the superconducting electron accelerator ELBE using a liquid lead circuit as photo-neutron target. By periodical sample-in-sample-out measurements the transmission of the sample materials has been determined using a low-threshold plastic scintillation detector. The resulting effective total cross sections show good agreement with previously measured data that cover only part of the energy range available at n ELBE. The results have also been compared to evaluated library files and recent calculations based on a dispersive coupled channel optical model potential. [ABSTRACT FROM AUTHOR]