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Concern about plastic pollution in coastal wetlands, seas and oceans has risen dramatically in recent years. Most of the waste found in the environment has a land-based origin and it is transported toward coastal-marine ecosystems through rivers and canals. Thus, waste collection in watercourses flowing through urban areas has a great potential to mitigate plastic pollution in local and coastal water bodies. In this paper, authors describe the results of three waste collection campaigns performed during 2021 (early summer, late summer and autumn) in three representative points of the channel network of the historical center of the city of Padova, Italy, where restoration efforts of the urban stream ecosystems are ongoing. The collected waste was analyzed both in terms of size and material type. A total of 418 kg of waste was collected: the prevailing fraction was the coarse one (59% of the material intercepted by a 100 mm side mesh sieve), and plastic represented the most abundant waste category (47% by weight). The total amount of litter produced in one year from the channel network of the city of Padova was estimated, with litter amounts on the canal banks found to be much higher than or at least comparable to those in water, a result which highlights the importance of planning waste collection together with riparian vegetation management to reduce plastic pollution. These findings provide a baseline for assessing the possibility to valorize the waste collected from the waterways of the city with processes other than landfilling and incineration

Migratory insects are key players in ecosystem functioning and services, but their spatiotemporal distributions are typically poorly known. Ecological niche modeling (ENM) may be used to predict species seasonal distributions, but the resulting hypotheses should eventually be validated by field data. The painted lady butterfly (Vanessa cardui) performs multigenerational migrations between Europe and Africa and has become a model species for insect movement ecology. While the annual migration cycle of this species is well understood for Europe and northernmost Africa, it is still unknown where most individuals spend the winter. Through ENM, we previously predicted suitable breeding grounds in the subhumid regions near the tropics between November and February. In this work, we assess the suitability of these predictions through i) extensive field surveys and ii) two-year monitoring in six countries: a large-scale monitoring scheme to study butterfly migration in Africa. We document new breeding locations, year-round phenological information, and hostplant use. Field observations were nearly always predicted with high probability by the previous ENM, and monitoring demonstrated the influence of the precipitation seasonality regime on migratory phenology. Using the updated dataset, we built a refined ENM for the Palearctic-African range of V. cardui. We confirm the relevance of the Afrotropical region and document the missing natural history pieces of the longest migratory cycle described in butterflies., This work was funded by the National Geographic Society (grant WW1-300R-18); by the British Ecological Society (grant LRB16/1015); by the Research and Conservation Projects of the Fundació Barcelona Zoo; by the grant PID2020-117739GA-I00/MCIN/AEI/10.13039/501100011033 of the Spanish Ministry of Science and Innovation and the Spanish State Research Agency to G.T.; by the grant LINKA20399 from the Spanish National Research Council iLink program to G.T., C.P.B., N.E.P., and R.V.; by fellowship FPU19/01593 of the program Formación de Profesorado Universitario (FPU) to A.G.-B.; by the Turkana Basin Institute, National Geographic Society, and Whitley Fund for Nature to D.J.M.; and by grant 2018-00738 of the New Frontiers in Research Fund (Government of Canada) to G.T. and C.P.B., Significance Abstract Results Field Surveys, Larval Hostplants, and Field-Based Model Validation Monitoring Results and Population Dynamics across Regions A Refined Model for the Afrotropical Region Discussion The Afrotropical Breeding Grounds of V. cardui: Multiple Generations Shift South Toward the Tropics Diversity and Phenology of Larval Hostplants in the Afrotropics The Ecological Relevance of Delimiting Spatiotemporal Distributions in Migratory Insects Conclusion Methods December-January Field Surveys and Year-Round Monitoring Spatiotemporal Ecological Niche Modeling Data, Materials, and Software Availability Acknowledgments Supporting Information References

Denosumab has proved effective at low doses in increasing bone mineral density in osteoporosis patients. In contrast to high-doses antiresorptive therapy, denosumab has a transient effect on the inhibition of the bone remodeling process, suggesting that denosumab-related osteonecrosis is a self-limiting disease, with a high curative potential of surgery when performed after a proper duration of receptor activator of nuclear factor-kB ligand (RANKL) inhibitor suspension. We report the long-term clinical and radiological (Computed Tomography—CT scan) data of a patient affected by secondary osteoporosis (cancer treatment-induced bone loss—CTIBL for metastatic breast cancer) who underwent surgical treatment for stage II denosumab-related osteonecrosis of the upper maxilla 7 months after denosumab suspension. A minimally invasive approach was performed with the extraction of the first right upper molar and debridement of the surrounding alveolar bone. After surgery, the patient was followed up at three-month intervals up to 1 year, and clinical and radiological data (CT scan) were recorded at each follow-up for the early detection of signs of recurrent disease. The mucosal healing remained stable in the long term, with radiological signs of bone remodeling in the post-operative site since the 6-month follow-up. The presented case strengthens the hypothesis that denosumab induces temporary alterations of bone turnover with a predictable curative effect of minimal surgical procedures in cases of denosumab-related osteonecrosis of the jaw.

The Italian Navy has always had, among its missions, the safeguard of the marine environment, and is strongly oriented to give its contribution to the targets fixed form the European Parliament with the European Green Deal. In 2012, the Italian Navy launched the Green Fleet initiative, with the aim of reducing greenhouse gas emissions and improving national energy security. To achieve these goals, the Italian Navy follows three main strategies: - adoption of a renewable synthetic fuel; - development and use of innovative eco-design technologies, which allow the reduction of the environmental impact of ships (LED lighting, SCR, foul release coatings); - adoption of energy saving operating procedures (electric propulsion, energy dashboard). The paper presents a case study focused on increasing the overall efficiency of a ship by recycling the thermal energy normally released to the environment by diesel engines. In fact, the overall efficiency of a diesel engine is about 40%, which means that 40% of the energy coming from the fuel is normally converted into usable power and the remainder is waste, which is delivered as heat to the environment. The case study identifies an effective solution to use a significant portion of that energy, while reducing the ship’s energy consumption, thereby increasing overall efficiency and reducing fuel consumption and greenhouse gas emissions during operations. At the same time, the identified technical solution makes possible to reduce electrical load peaks, making the electrical load diagram more homogeneous, with the further result of optimizing the working conditions of the diesel engines.

A região que abrange as bacias hidrográficas dos rios Piracicaba, Capivari e Jundiaí (PCJ) demonstra uma crescente demanda na explotação e uso das águas subterrâneas, que acompanha o aumento populacional e da urbanização. Levantamentos regionais indicam cenários de limitações na disponibilidade hídrica subterrânea associados a grandes volumes de águas extraídos, mostrando a necessidade de um acompanhamento, também em escala local, sobre a situação do uso dos recursos hídricos. Nesse sentido, este trabalho teve como proposta avaliar os dados existentes e disponíveis sobre a água subterrânea, em escala municipal, com o intuito de elaborar um diagnóstico sobre a sustentabilidade do uso da água. Selecionou-se o município de Sumaré-SP, por estar inserido em área crítica quanto à disponibilidade hídrica e por contemplar no seu Plano Diretor diretrizes para a gestão ambiental integrada. A partir de dados de cadastros oficiais de poços, foram avaliados os aquíferos mais explotados quanto a: potencialidade hídrica (vazões e capacidades específicas médias e medianas, profundidade dos poços e dos níveis d’água), finalidades de uso da água, densidade de poços e intensidade de extração de água subterrânea e saldo hídrico. A constatação de existência de áreas onde ocorre déficit hídrico levou a recomendações como o aprofundamento nos estudos hidrogeológicos, assim como o acompanhamento da evolução da situação da explotação hídrica no município e de ocorrência de conflitos de uso.

Orientador: Regina Maria Puppin-Rontani Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba Resumo: O objetivo neste estudo foi avaliar o efeito de diferentes pastas obturadoras e agentes de limpeza sobre a dentina radicular de dentes decíduos, sobre: a estrutura molecular; e a morfologia de superfície da dentina radicular em dentes decíduos. Foram utilizadas 80 raízes de dentes decíduos anteriores extraídos por razões clínicas. As coroas foram seccionadas na junção cemento-esmalte e descartadas; e as raízes seccionadas no sentido longitudinal expondo os condutos radiculares, as quais foram planificadas e sonicadas. As raízes foram fixadas com resina composta para facilitar o manuseio, em seguida os condutos foram instrumentados com limas tipo K (15 a 35) e irrigados a cada troca de lima com hipoclorito de sódio a 0,5% + EndoPTC. Então, os espécimes foram distribuídos em 4 grupos de acordo com as pastas obturadoras (n=20): Controle-CP (sem obturação), Calen® espessada com óxido de zinco-CZ, Calcipex II®-CII, Vitapex®-V. Após a obturação, os espécimes foram armazenamentos por 7 dias. Após esse período, as pastas obturadoras foram removidas e os espécimes foram subdivididos em 4 grupos de acordo com os agentes de limpeza (n=5): Controle-CL (Sem limpeza), Etanol-E, Tergenform®-T, Ácido fosfórico-AF 35%...Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digital Abstract: The aim of this study was to verify the effect the different filling pastes and cleaning agents in primary dentin root, as: molecular structure and morphologic structure the surface of root dentin in primary teeth. For the study were used 80 anterior primary teeth roots extracted for clinical reasons. The crowns of the teeth were sectioned at cement enamel junction and discarded. The roots were separated longitudinally exposing the root canal, which were ground flat and sonicated. The specimens were fixed using composite resin to facilitate manipulation, and then they were prepared with K-type files size #15-35 and irrigated with of 0.5% sodium hypochlorite solution + EndoPTC cream. Thus, were divided into 4 groups (n=20) according to the filling pastes: Control (without filling), Calen® paste thickened with zinc oxide, Calcipex II®, Vitapex®. Then, the specimens were stored for seven days. After that, filling paste was removed and the specimens were subdivided into 4 cleaning agents groups (n=5): Control (without cleaning agents), Ethanol, Tergenform®, Phosphoric acid (35%)...Note: The complete abstract is available with the full electronic document Mestrado Odontopediatria Mestre em Odontologia

The abandonment of agricultural land and the afforestation of grassland habitats represent major threats for butterflies in European and Mediterranean areas. A crucial goal for Lepidoptera conservation is to maintain and/or restore habitat quality by targeted management. Nevertheless, there are few experimental studies allowing to derive data-driven strategies to protect butterflies of open grasslands in the Mediterranean region. We developed a habitat management strategy for the conservation of the Italian endemic butterfly Zerynthia cassandra by adopting a three-step procedure: (i) characterising which environmental and host plant features influence oviposition on plants; (ii) identifying and testing the effect of a data-driven habitat management intervention; (iii) understanding which micro-habitat features promote Z. cassandra oviposition in restored places to optimise the intervention. Both patch (areas of 1 m radius hosting Aristolochia shoots) and plant features affect oviposition, with the strongest positive effects showed by high irradiation of the patch and plant quality (high number of flowers and leaves). Accordingly, the management consisted in vegetation cuts to increase irradiation, and 2 years of monitoring demonstrated that this procedure significantly increased oviposition (average increase of about 2 eggs per plant) and larval presence. Micro-habitat sampling demonstrated that the maximum oviposition differed between vegetation structures, highlighting the importance of a local fine-tuning before the intervention. We provided a data-driven, effective, and sustainable management strategy to increase habitat suitability and oviposition for an endemic and endangered Mediterranean butterfly. Our framework can drive management strategies for other species with similar ecological requirements and subjected to similar threats.

In this study, the wettability, cell viability, and roughness of an experimental dense bovine hydroxyapatite [Ca10(PO4)6(OH)2] ceramic block were evaluated so that, in the future, it could be used as a base material for dental implants. The results to commercial zirconia and a commercially pure titanium (Ti) alloy were compared. The surface roughness and contact angles were measured. An in vitro evaluation was conducted by means of tests in which pre-osteoblastic MC3T3-E1 cells were placed in indirect and direct contact with these materials. For cell viability, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and crystal violet test were conducted. A qualitative analysis was conducted using variable pressure scanning electron microscopy (SEM). No statistically significant differences were observed in wettability and roughness tests among the groups. In both the MTT assay and crystal violet test, all groups demonstrated satisfactory results without cytotoxicity. SEM showed cell adhesion and cell proliferation results on the material surfaces after 24 h and 48 h. In conclusion, this dense Ca10 (PO4)6(OH)2 ceramic can be considered as a potential biocompatible material.

This study investigates the major chemical components, particle-bound water content, acidity (pH), and major potential sources of PM

A total of 85 PM2.5 samples were collected at a site located in a large industrial zone (Porto Marghera, Venice, Italy) during a 1-year-long sampling campaign. Samples were analyzed to determine water-soluble inorganic ions, elemental and organic carbon, and levoglucosan, and results were processed to investigate the seasonal patterns, the relationship between the analyzed species, and the most probable sources by using a set of tools, including (i) conditional probability function (CPF), (ii) conditional bivariate probability function (CBPF), (iii) concentration weighted trajectory (CWT), and (iv) potential source contribution function (PSCF) analyses. Furthermore, the importance of biomass combustions to PM2.5 was also estimated. Average PM2.5 concentrations ranged between 54 and 16 μg m−3 in the cold and warm period, respectively. The mean value of total ions was 11 μg m−3 (range 1–46 μg m−3): The most abundant ion was nitrate with a share of 44 % followed by sulfate (29 %), ammonium (14 %), potassium (4 %), and chloride (4 %). Levoglucosan accounted for 1.2 % of the PM2.5 mass, and its concentration ranged from few ng m−3 in warm periods to 2.66 μg m−3 during winter. Average concentrations of levoglucosan during the cold period were higher than those found in other European urban sites. This result may indicate a great influence of biomass combustions on particulate matter pollution. Elemental and organic carbon (EC, OC) showed similar behavior, with the highest contributions during cold periods and lower during summer. The ratios between biomass burning indicators (K+, Cl−, NO3 −, SO4 2−, levoglucosan, EC, and OC) were used as proxy for the biomass burning estimation, and the contribution to the OC and PM2.5 was also calculated by using the levoglucosan (LG)/OC and LG/PM2.5 ratios and was estimated to be 29 and 18 %, respectively.

To evaluate physical-chemical properties of experimental diacetate chlorhexidine (CHX)-added resin blends.Blends were formulated: G1)TEGDMA; G2)TEGDMA/0.1%CHX; G3)TEGDMA/0.2%CHX; G4)TEGDMA/UDMA; G5)TEGDMA/UDMA/0.1%CHX; G6)TEGDMA/UDMA/0.2%CHX; G7)TEGDMA/BisEMA, G8)TEGDMA/BisEMA/0.1%CHX; G9)TEGDMA/BisEMA/0.2%CHX. Icon(®) was the control group. For sorption/solubility (SS), cylindrical specimens (n=5) were prepared and their weight obtained. The specimens were immersed in deionized water for 7days at 37°C and their weight was verified again. SS were calculated using accepted formulas. For softening, cylindrical specimens (n=10) were prepared and initial Knoop hardness number (KHN) obtained. The specimens were immersed in absolute ethanol for 24h at 37°C and final KHN accomplished. Softening values were calculated by KHN reduction percentage. For elastic modulus (EM) and flexural strength (FS) bar specimens were prepared (n=10) and values obtained with a universal device (three point, 5mm distance, 0.5mm/min, load of 50N). The data was analyzed using one-way ANOVA and Tukey test (α=5%).TEGDMA/BisEMA blends and Icon(®) showed the lowest sorption from blends (p0.05), and Icon(®) was the most soluble material (p0.01). TEGDMA/UDMA/0.1%CHX showed the highest softening, similar to Icon(®) (p0.05). For EM, all blends were different than Icon(®) (p0.01). For FS, TEGDMA blends were similar to Icon(®), showing the lowest averages (p0.05).Monomers chemical characteristics influenced the physical-chemical properties of experimental blends more than CHX. Between the blends tested, UDMA blends presented satisfactory results for assays evaluated.Infiltrants CHX-added could arrest and reinforce initial caries lesions, and the antimicrobial effect could prevent new lesions in sound enamel adjacent to the infiltrated area.

Understanding host plant preference and the relative quality of resource provided by co-occurring host plants is a key step to predict butterfly species abundance and responses to environmental changes, and, consequently, to plan management measures. Zerynthia cassandra is an Italian endemic species strongly dependent on the availability of its host plants, Aristolochia rotunda and Aristolochia lutea. The insular population occurring on Elba island (Tuscan Archipelago) is highly threatened, because of limited host plant distribution, small population size and apparent lack of gene flow with the mainland. In 2017, we carried out field surveys and rearing experiments to (i) identify the characteristics of the host plants (vegetative status) and the site characteristics (aspect, irradiation, distance from other patches) correlated with the number of eggs occurring on individual plants, (ii) compare larval growth, food-conversions rate and larval and adult survivorship on the two host plants species. Egg occurrence depends on patch irradiation, the number of leaves and flowers occurring on individual plants and the occurrence of nearby patches. These findings allowed to identify the optimal Aristolochia patch features for egg laying and development. Laboratory rearing success was higher than 50% and although plant species did not show a significant effect on oviposition, we found that larval and adult survival was higher on A. rotunda. Our results suggest habitat management aimed at increasing resource availability for Z. cassandra and possible ex-situ conservation actions aimed at recovering the population in case of potential catastrophic events.

The Veneto region lies in the eastern part of the Po Valley (Italy). This is one of the hotspots in Europe for air quality, where efforts to meet the European standard for PM2.5 according to current and future legislation have been generally unsuccessful. Recent data indicating that ammonium, nitrate and sulphate account for about one third of total PM2.5 mass show that secondary inorganic aerosol (SIA) plays a key role in the exceedence of the standards. A sampling campaign for PM2.5 was carried out simultaneously in six major cities (2012–2013). The water soluble inorganic ions were quantified and data processed to: (1) investigate the seasonal trends and the spatial variations of the ionic component of aerosol; (2) identify chemical characteristics at the regional-scale and (3) assess the potential effects of long-range transport using back-trajectory cluster analysis and concentration-weighted trajectory (CWT) models. Results indicated that PM2.5 and SIA ions have an increasing gradient in concentrations from North (mountain) to South (lowland) and from East (coastal) to West (more continental), whereas K+ and Ca2+ levels are quite uniformly distributed. Similar seasonal trends in PM2.5 and ions are seen across the region. Simultaneous daily changes were observed and interpreted as a consequence of similar emission sources, secondary pollutant generation and accumulation/removal processes. Sulphate and nitrate were not directly related to the concentrations of their precursor gases and were generally largely, but not completely, neutralised by ammonium. The clustering of back-trajectories and CWT demonstrate that the long-range movement of the air masses has a major impact upon PM2.5 and ion concentrations: an area spreading from Eastern to Central Europe was identified as a main potential source for most ions. The valley sites are also heavily influenced by local emissions in slow moving northerly air masses. Finally, two episodes of high nitrate levels were investigated to explain why some sites are experiencing much higher concentrations than others. This study identifies some key features in the generation of SIA in the Po Valley, demonstrating that SIA generation is a regional pollution phenomenon and mitigation policies are required at regional, national and even European scales.

The Po Valley is one of the most important hot spots in Europe for air pollution. Morphological features and anthropogenic pressures lead to frequent breaching of air quality standards and to high-pollution episodes in an ~46 × 10

Objective Frontonasal dysplasia is a rare developmental defect of the midface, and little is known about the dental involvement in individuals with this condition. This study investigated tooth abnormalities and occlusal disorders in individuals with frontonasal dysplasia. Design Cross-sectional. Setting Hospital for Rehabilitation of Craniofacial Anomalies, University of São Paulo, Bauru, Brazil. Interventions Clinical oral examination, analysis of patient records, and panoramic radiographs. Participants A total of 20 individuals with frontonasal dysplasia aged 7 to 17 years. Main Outcome Measures Prevalence of the several tooth abnormalities and occlusal disorders analyzed. Results A total of 19 individuals presented at least one tooth abnormality, with highly variable findings. In radiographs, 20% of individuals (all presenting oral clefts) presented agenesis of lateral incisors and second premolars. No supernumerary teeth were observed; 65% of individuals exhibited occlusal alterations, especially anterior open bite in the two individuals with median cleft lip. Conclusions Variable clinical and radiographic alterations were observed, probably due to the large variety of phenotypic characteristics. No specific dental alteration could be related with frontonasal dysplasia.

Orientadores: Regina Maria Puppin Rontani, Fernanda Miori Pascon Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba Resumo: O uso do infiltrante Icon® tem mostrado eficácia ao redor de 60% quando aplicado em lesões iniciais de cárie, em relação à progressão das mesmas. Entretanto, foi observada alta rugosidade de superfície após a aplicação sobre lesões de mancha branca, podendo aumentar o acúmulo de biofilme dental sobre a superfície e assim comprometer a longevidade do procedimento. A adição de um agente antimicrobiano como o diacetato de clorexidina (CHX) ao material infiltrante (Icon®) poderia auxiliar no controle da adesão do biofilme na superfície do material, evitando a reincidência de lesões cariosas ou a progressão das mesmas, e também aumentar a eficácia da terapêutica. Deste modo, o objetivo desta Tese foi avaliar o efeito da adição de CHX no infiltrante Icon® em relação: a atividade antimicrobiana, por meio de teste de difusão em ágar (n=3); a rugosidade de superfície dos infiltrantes antes e após o processo de biodegradação (n=10); o grau de conversão (n=10); a dureza Knoop e amolecimento do polímero (n=10); o módulo de elasticidade (n=12); o coeficiente de penetração por meio do ângulo de contato (n=10); e a sorção e a solubilidade em água (n=5). A densidade de ligações cruzadas foi avaliada indiretamente através da taxa de redução de dureza após imersão em etanol. Neste estudo foram utilizados três grupos: infiltrante Icon®, Icon® + 0,1% CHX e Icon® + 0,2% CHX. Os dados de biodegradação foram submetidos à ANOVA para medidas repetidas dois critérios e teste de Tukey (?=5%) fatores de estudo foram o material e o tempo; os dados de ângulo de contato foram submetidos à ANOVA dois critérios e teste de Tukey (?=5%) fatores de estudo foram material e superfície; e os demais dados a ANOVA um critério, e teste de Tukey (?=5%). O Icon® não apresentou atividade antimicrobiana no teste de difusão em ágar para Streptococcus mutans e Lactobacillus acidophillus; a adição de CHX a 0,1 e 0,2% apresentou efeito antimicrobiano e não diferiram significativamente entre si, para ambas as cepas (p>0,05). Após a biodegradação a superfície do grupo Icon® apresentou maior rugosidade quando comparada aos grupos com adição de CHX (p0,05). As análises de módulo de elasticidade, dureza Knoop e sorção de água apresentaram maiores valores para os grupos com adição de CHX (p

Fifty patients were scheduled to undergo removal of symmetrically positioned lower third molars in two separate appointments. Meloxicam 7.5 or 15 mg was once daily administered in a double-blind, randomized and crossover manner after the surgery for 4 days. Objective and subjective parameters were recorded for comparison of postoperative courses. Patients treated with 7.5mg meloxicam who underwent osteotomy reported higher pain scores at 1.5, 3, 4, 10, 12 and 16 h (P0.05) and ingested a greater amount of rescue analgesic medication (P0.05) than those who did not require osteotomy. A higher percentage of patients who underwent osteotomy medicated with 7.5mg meloxicam needed rescue medication as compared to those who did not require osteotomy (P0.05). There was a similar mouth opening at suture removal compared with preoperative values for both doses (P0.05). There were no significant differences concerning swelling observed on the 2nd or 7th postoperative days in comparison with baseline (P0.05) between the two doses. Pain, trismus and swelling after lower third molar removal not requiring osteotomy can be successfully controlled by a dose regimen of 7.5mg meloxicam once daily. For more aggressive extractions 15 mg meloxicam is advisable.

Nouns and verbs can dissociate following brain damage, at both lexical retrieval and morphosyntactic processing levels. In order to document the range and the neural underpinnings of behavioral dissociations, twelve aphasics with disproportionate difficulty naming objects or actions were asked to apply phonologically identical morphosyntactic transformations to nouns and verbs. Two subjects with poor object naming and 2/10 with poor action naming made no morphosyntactic errors at all. Six of 10 subjects with poor action naming showed disproportionate or no morphosyntactic difficulties for verbs. Morphological errors on nouns and verbs correlated at the group level, but in individual cases a selective impairment of verb morphology was observed. Poor object and action naming with spared morphosyntax were associated with non-overlapping lesions (inferior occipitotemporal and fronto-temporal, respectively). Poor verb morphosyntax was observed with frontal-temporal lesions affecting white matter tracts deep to the insula, possibly disrupting the interaction of nodes in a fronto-temporal network.

Background Flow cytometric analysis of leukemia-associated immunophenotypes and polymerase chain reaction-based amplification of antigen-receptor genes rearrangements are reliable methods for monitoring minimal residual disease. The aim of this study was to compare the performances of these two methodologies in the detection of minimal residual disease in childhood acute lymphoblastic leukemia. Design and Methods Polymerase chain reaction and flow cytometry were simultaneously applied for prospective minimal residual disease measurements at days 15, 33 and 78 of induction therapy on 3565 samples from 1547 children with acute lymphoblastic leukemia enrolled into the AIEOP-BFM ALL 2000 trial. Results The overall concordance was 80%, but different results were observed according to the time point. Most discordances were found at day 33 (concordance rate 70%) in samples that had significantly lower minimal residual disease. However, the discordance was not due to different starting materials (total versus mononucleated cells), but rather to cell input number. At day 33, cases with minimal residual disease below or above the 0.01% cut-off by both methods showed a very good outcome (5-year event-free survival, 91.6%) or a poor one (5-year eventfree survival, 50.9%), respectively, whereas discordant cases showed similar event-free survival rates (around 80%). Conclusions Within the current BFM-based protocols, flow cytometry and polymerase chain reaction cannot simply substitute each other at single time points, and the concordance rates between their results depend largely on the time at which they are used. Our findings suggest a potential complementary role of the two technologies in optimizing risk stratification in future clinical trials.

Although it is the treatment of choice in the management of idiopathic Parkinson's disease, l-DOPA (LD) shows a decline in its efficacy after years of prolonged use, with the appearance of severe motor disturbances. These complications have been interpreted on pharmacokinetic and pharmacodynamic grounds. The main pharmacokinetic reason is considered to be the decreased capacity in LD activation to dopamine along with reduction of its storage ability in the nigrostriatal terminals, as a result of disease progression. At this stage the LD action in the extrapyramidal system is thought to be closely dependent on its synaptic cleft concentrations, being directly related to those in the systemic circulation and to the events possibly perturbing them. Therapeutic drug monitoring might be useful to explain these modifications in relation to the clinical effect and even to possible problems in transport competition and so to define the LD dosage regimen. Recently LD threshold concentrations have been suggested by means of sophisticated pharmacokinetic-pharmacodynamic approaches. Unfortunately they do not correspond to real therapeutic ranges but to levels in a hypothetical effect compartment in no steady-state conditions, due to remarkable LD fluctuations. However they are considered helpful to the functional state interpretation of the nigrostriatal system.

Background: Single-laboratory experience showed that flow cytometric (FCM) assessment of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) is feasible in most patients and gives independent prognostic information. It is, however, not known whether FCM analysis can reliably be standardized for multicentric application. Methods: An extensive standardization program was installed in four collaborating laboratories, which study FCM-MRD in children treated with the AIEOP-BFM-ALL 2000 protocol. This included methodological alignment, continuous quality monitoring, as well as personnel education by exchange and performance feed-back. Results: Blinded inter-laboratory tests of list-mode data interpretation concordance (n = 202 blood and bone marrow samples from follow-up during induction of 31 randomly selected patients of a total series of n = 395) showed a very high degree of inter-rater agreement among the four centers despite differences in cytometers and software usage (intraclass correlation coefficient [ICC] 0.979 based on n= 800 single values). Lower concordance was reached with amounts of MRD below 0.1%. Comparing data from sample exchange experiments (n = 42 samples; ICC 0.98) and from independent patient cohorts from the four centers (regarding positive samples per time-point of follow-up as well as risk estimates) concordance was also good. Conclusion: MRD-evaluation by FCM in ALL can be standardized for reliable multicentric assessment in large trials. © 2008 Clinical Cytometry Society.

Since motor fluctuations in Parkinsonian patients might be, at least in part, explained by an antagonism between levodopa (LD) and its metabolite 3-O-methyldopa (3-OMD) at blood-brain-barrier (BBB), we decided to study LD and 3-OMD plasma and cerebrospinal fluid (CSF) levels in subjects undergoing lumbar puncture for diagnostic purposes. After informed consent, 70 subjects took a tablet of carbidopa-levodopa association (Sinemet or Sinemet-CR) 0.5, 1, 2, 4, 8, 12h before blood and lumbar cerebrospinal fluid collection. LD and 3-OMD were determined by an HPLC-electrochemical method. The subjects treated with Sinemet-CR had lower LD cerebrospinal fluid concentrations along with lower LD and higher 3-OMD plasma concentrations. This pattern of LD cerebrospinal fluid concentrations may be explained by means of a transport competition between LD and 3-OMD at blood brain barrier level.

The paper reports plasma levels of levodopa (LD), its main metabolites [dopamine, dihydroxyphenylacetic acid, homovanillic acid, 3-O-methyldopa (3-O-MD)] and carbidopa in 14 parkinsonian patients first treated with Sinemet and thereafter with Sinemet-CR4. A good relationship was observed between LD plasma levels and pharmacological effects. While the LD area under the curve increased after Sinemet-CR4, the same was not observed with metabolites, except with 3-O-MD. The experiments in volunteer subjects confirmed the increase in 3-O-MD in plasma after Sinemet-CR4. Higher levels were observed also in the CSF with a reduction of LD concentrations. This seems to corroborate the hypothesis of an interference with LD passage through the blood-brain barrier in humans.

Summary: Purpose: To study the interaction between gaba-pentin (GBP) and high-protein meals, 12 patients with epilepsy were administered this drug both while in a fasting state and after a high-protein meal. Methods: After having acquired their informed consent, the patients (suffering from partial complex seizures resistant to other anticonvulsants) were randomly assigned to 2 groups of 6 subjects. Each subject was treated in a fasting state with a single 400 (group A) or 800 (group B) mg GBP oral dose. After 24 h, the GBP dose regimen was repeated, but was given after a high-protein meal. Serum GBP concentrations were measured by LC-Mass at baseline and 0.5, 1, 2, 3, 5, 7, 9, 12, and 24 h. Saliva GBP concentrations were determined at baseline and 2, 4, 8, and 12 h. GBP urinary excretion was determined at 0–4, 4–8, and 8–12 h intervals. The following kinetic parameters were calculated: area under the concentration time curve from zero time to 24 h after the dose, AUC 0–24 h; maximal serum concentration, Cmax; time to the maximal serum concentration, Tmax; absorption rate constant, ka; elimination rate constant, p; elimination half-time, t½β. Student's t test for paired data, with significance assigned at P < 0.05, was used. Results: No statistically significant differences were seen in GBP serum or saliva concentrations or in its urinary excretion (both in A or B group) between fasting and after the high-protein meal. Conclusions: High-protein meals do not seem to interfere with oral disposition of GBP.

We compared the clinical efficacy of orally administered valdecoxib and piroxicam for the prevention of pain, trismus and swelling after removal of horizontally and totally intrabony impacted lower third molars. Twenty-five patients were scheduled to undergo removal of symmetrically positioned lower third molars in two separate appointments. Valdecoxib (40 mg) or piroxicam (20 mg) was administered in a double-blind, randomized and crossed manner for 4 days after the surgical procedures. Objective and subjective parameters were recorded for comparison of postoperative courses. Both agents were effective for postoperative pain relief (N = 19). There was a similar mouth opening at suture removal compared with the preoperative values (86.14 +/- 4.36 and 93.12 +/- 3.70% of the initial measure for valdecoxib and piroxicam, respectively; ANOVA). There was no significant difference regarding the total amount of rescue medication taken by the patients treated with valdecoxib or piroxicam (173.08 +/- 91.21 and 461.54 +/- 199.85 mg, respectively; Wilcoxon test). There were no significant differences concerning the swelling observed on the second postoperative day compared to baseline measures (6.15 +/- 1.84 and 8.46 +/- 2.04 mm for valdecoxib and piroxicam, respectively; ANOVA) or on the seventh postoperative day (1.69 +/- 1.61 and 2.23 +/- 2.09 mm for valdecoxib and piroxicam, respectively; ANOVA). The cyclooxygenase-2 selective inhibitor valdecoxib is as effective as the non-selective cyclooxygenase inhibitor piroxicam for pain, trismus and swelling control after removal of horizontally and totally intrabony impacted lower third molars.

Sixty patients, all potential candidates for ongoing lamotrigine (LTG) treatment as add-on therapy for resistant partial seizures and receiving carbamazepine (CBZ) and/or valproate (VPA) treatment, were submitted to therapeutic drug monitoring (TDM). The aim was to evaluate the possible relation between serum levels and the clinical effect of LTG, to verify whether CNS toxicity has to be considered the result of a pharmacokinetic or a pharmacodynamic interaction with CBZ, and to investigate whether possible changes in the clinical response during long-term treatment are dependent on LTG serum level variations. Sixteen patients achieved complete control, 26 a ≧50% reduction in seizures, the remainder did not respond. Mean LTG serum concentrations were higher in responders than in nonresponders, the difference being statistically insignificant. The best results were observed in VPA-cotreated patients with the highest LTG blood levels. CNS toxicity occurred after giving LTG to subjects who subsequently developed the highest LTG concentrations, whereas CNS toxicity seemed unrelated to CBZ and CBZ-epoxide serum concentrations. No decrease in LTG, CBZ and VPA serum levels was observed even in patients showing a reduction in the response during long-term treatment.

The pharmacokinetics of chlorpromazine after intravenous infusion were studied in 25 children. The pharmacokinetic parameters studied are markedly different from those reported for adults. A clear relationship was demonstrated between age, serum terminal half-life (r = 0.75) and systemic clearance (r = -0.43). It appears that the pharmacokinetics of chlorpromazine are more rapid in children than in adults.

Notwithstanding pharmacokinetics has greatly increased the rational approach to the drug treatment of epilepsies, about 25% of the patients do not respond to the therapy. Therefore, a great effort has been made to discover new antiepileptic drugs effective in refractory seizures. On the basis of increased knowledge of seizure pathophysiology two principal groups of drugs have been developed: the first enhancing brain GABA activity (vigabatrin); the second inhibiting excitatory amino-acids (lamotrigine and felbamate). Oxcarbazepine has the same mechanism of action as carbamazepine, whereas gabapentin's mechanism is still uncertain. The major clinical indications of these new antiepileptic drugs are represented by partial complex seizures. Side effects (mostly regarding the central nervous system) appear mild, and clinical interactions have little importance. The role of therapeutic drug monitoring for these substances is at present not well established.

A case of type I Arnold-Chiari malformation, with onset of diplopia, without associated medullar alteration, is presented. The symptomatology remained unique and had transitory presentation for many years with negative ophthalmic examinations. Attention is drawn to the great variability of the syndrome's presenting symptoms confirming the importance of MR in the diagnostic course and of evoked potentials of the brain stem to follow progress of the illness.

Pharmacokinetics has greatly contributed to the elucidation of the variability in clinical response to antidepressants in terms of differences in plasma concentrations due to genetic constitution, age, associated diseases and drug interactions. Despite no general agreement, therapeutic and toxic concentrations have been suggested for some tricyclic antidepressants (TCAs) [amitriptyline, nortriptyline, imipramine, desipramine]. Predictive techniques may be implemented on the basis of which starting TCA dosages may be selected to reach more rapidly those concentrations at which efficacy is more probable. Therapeutic drug monitoring may thereafter assist the clinician in refining the individualisation of the dosage regimen.

Pharmacokinetics of single dose (25 mg i.m.) of imipramine was studied in geriatric and young adult patients with mood disorders requiring antidepressant treatment. Imipramine and its principal metabolites were determined by means of a high performance liquid chromatography method with electrochemical detection. Serum concentrations analysis was performed according to a bicompartmental open model. A relationship between age and kinetic parameters such as area under the curve, elimination phase constant, half-life and total body clearance was observed. Significant differences were demonstrated between elderly and young adult patients when comparing these parameters. It is concluded that geriatric patients treated with imipramine should receive doses of about 60% of those of young adults.

Antidepressants, especially tricyclic agents (TCAs), are increasingly used in geriatric patients since depression is a common mood disorder in the elderly and the size of elderly population is increasing. Notwithstanding the importance of kinetics to better use of drugs, its study in the elderly (regarding WAS) is not sufficiently developed. The present paper briefly reviews the available data on amitriptyline, nortriptyline, protriptyline, imipramine, desipramine and clomipramine kinetics in the elderly.

Early measurement of blast clearance is a relevant prognostic indicator in childhood acute lymphoblastic leukemia (ALL). To this purpose we measured, by four-colour flowcytometry (FC), the percentage of blast cells in bone marrow samples from Italian patients enrolled in the multicentre AIEOP-BFM ALL 2000 trial. Samples were collected on day 15 (after 14 days of steroids, and one dose of IT-MTX, vincristine, daunorubicine, asparaginase) and shipped overnight to the reference laboratory. The data were compared to PCR-MRD performed, by study design, on day +33 and +78 BM samples. We report the results of patients enrolled between December 2000 and October 2004. The 561 patients studied were not different from the remaining ones (with no available material) including their cumulative incidence of relapse (SE): 17.3% (1.9) vs. 18.1% (1.5) in 850 patients not studied. According to the results of FC-MRD, 5 groups were defined: negative (blast count 10% (n=56). Their cumulative 5-year risk of relapse was: 4.1% (1.9), 9.3% (4.0), 14.3% (3.2), 26.5% (5.5), 53.7% (7.4), respectively. By PCR-MRD, the same patients were stratified as follows: 177 were standard risk and had 5-year risk of relapse of 4.1% (1.7), 233 at intermediate risk had a relapse risk of 24.2% (3.4), 37 at high risk had a relapse risk of 58.1% (9); the remaining 124 patients (21.6%) were not stratified by PCR-MRD due to lack of 2 sensitive (≥10−4) markers. Of 177 patients classified as standard risk by PCR (double negative), 110 fell within the 2 subgroups with lower FC-MRD (10% of blasts. Of the 233 patients stratified as PCR-MRD intermediate risk (d78 10% blasts. These groups had a risk of relapse of 6.2% (1.9), 19.5% (3), and 53.7% (7.4), respectively. Since it is fast, reproducible, relatively cheap and applicable to virtually all patients, our group decided to apply it prospectively on all ALL patients to integrate PCR-based stratification. Our findings showed that: early (d15) MRD detection by FCM identifies different patients than PCR on d33 and d78; FCM may be very useful to identify earlier the highly sensitive ALL with low relapse risk (even though long-term follow-up is still missing), whereas later timepoints may be accessible for PCR and the identification of HR patients.

This paper shows the possibility of using an interline transfer (and floating gate) imaging CCD as X-ray and charged particle detector, running at standard TV rate (7.16 MHz) and room temperature (296 K). Experimental tests have been made using a Fairchild CCD 222 with exposures to 55 Fe, 90 Sr, 241 Am radiation sources. The CCD is linked to a personal computer through a video processor and the events are filtered and analyzed by digital image processing. The rms noise has been measured as a function of the temperature obtaining about 87 electrons/pixel at 296 K.

A high-pressure liquid chromatographic (HPLC) method for the serum assay of benperidol is described. One ml of serum is required for a single estimation. The method involves a simple and rapid extraction step (BondElut columns), HPLC separation (C8 10-mu column), and electrochemical detection (+0.65 V). Haloperidol is used as internal standard. On the basis of this procedure, recovery (93-97%) and reproducibility (intra-assay and inter-assay coefficients of variation less than 9%) are satisfactory. The detection limit is 0.2 ng/ml of serum. After therapeutic doses, trough serum levels ranged from 3.8 to 12 ng/ml in five patients.

Thirty-seven children (6-13 years old), receiving a flexible dosage of imipramine (IMI) for nocturnal enuresis, were evaluated. After a mean time of 8.5 +/- 7.0 weeks of therapy, 40.5% no longer wet the bed; 32.4% had a mean benefit of 80%; 27.01% had a negligible response. The best relationship observed was between clinical effect and drug serum concentrations rather than with drug daily dose, the most satisfactory being that with IMI seric values (P = 0.019). Responders (effect higher than 50%) had higher IMI serum concentrations (P less than 0.05) than poor responders. At 3 and 6 months after stopping the drug, over 90% of the responders maintained the maximum response reached during treatment. The side-effects observed were irritability, reduction of appetite, headache, a mild increase of blood pressure.