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The levels of non-dioxin-like PCB indicators (iPCBs 28, 52, 101, 138, 153, and 180) were determined in food samples (seafood, meat and processed meat, milk and dairy products, hen eggs, olive oil, and other fats) to evaluate the exposure of adult and elderly population. iPCB levels in samples were in the following order: fishery products > meat and processed meat > milk and dairy products > olive oil and other fats. None of the samples had concentrations above the maximum permissible limits for human consumption established by the European Union legislation, except for salami samples. The dietary intake for the total population was 12.33 ng·kg−1 bw·d−1, while depending on the sex/age groups, exposure was estimated between 9.60 and 12.11 ng·kg−1 bw·d−1, with seafood being the major contributor. The exposure scenario indicates that further efforts must still be carried out to protect the consumer from these harmful chemicals.

Aim: This case report aims to illustrate a clinical protocol that allows for the rehabilitation of patients requiring extensive osteotomy, simultaneous implant placement, and full-arch, screwed-in prosthetics in one session. This protocol allows for the improvement of the aesthetics and functionality of the fixed implant-supported prosthesis through the preoperative planning of all surgical procedures, including osteotomy, and of the prosthesis through the application of 3D-printing technology for the creation of surgical templates and prostheses. Methods: This case report concerns a 72-year-old patient, ASA1, who, following diagnosis, the establishment of a treatment plan, and the provision of informed consent, opted for an immediate, full-arch rehabilitation of the lower arch. The digital planning stage started with the correct positioning of the fixtures. The proper bone levels were found and used to guide the creation of the provisional screwed-in prothesis. Two templates with the same supports (landmarks/pins) were then 3D-printed: a positioning template, including a slit to assist the surgeon during the osteotomy, and a surgery template to assist the surgeon during the implants’ positioning. A screwed-in prosthesis encased in resin C&B MFH (NEXTDENT®, Soesterberg, The Netherlands) was delivered. Minimal occlusal adjustments were performed. Results: In a single clinical session, through careful planning and the pre-operative 3D printing of a prosthesis, a temporary implant-supported prosthetic rehabilitation was possible in a case that required an extended osteotomy. Clinically, the correspondence between the virtual design phase and the final realization was consistent. At a functional level, the provisional prosthesis required minimal occlusal adjustments and the DVO values obtained in the immediate post-operative period were found to be comparable to those of the virtual design. By planning the final position of the bone and the implants in advance, it was possible to deliver a full-arch prothesis with proper implant emergence, occlusal vertical dimensions, and occlusal relationship. Conclusion: This fully digital protocol allows the clinician to preview and plan the osteotomy and implant surgery as well as the delivery of the temporary, immediately loaded, complete, fixed prosthesis in patients who are candidates for post-extraction surgery with the need for severe osteotomy.

Physiologically based pharmacokinetic models, populated with drug-metabolizing enzyme and transporter (DMET) abundance, can be used to predict the impact of hepatic impairment (HI) on the pharmacokinetics (PK) of drugs. To increase confidence in the predictive power of such models, they must be validated by comparing the predicted and observed PK of drugs in HI obtained by phenotyping (or probe drug) studies. Therefore, we first predicted the effect of all stages of HI (mild to severe) on the PK of drugs primarily metabolized by cytochrome P450 (CYP) 3A enzymes using the default HI module of Simcyp Version 21, populated with hepatic and intestinal CYP3A abundance data. Then, we validated the predictions using CYP3A probe drug phenotyping studies conducted in HI. Seven CYP3A substrates, metabolized primarily via CYP3A (fraction metabolized, 0.7-0.95), with low to high hepatic availability, were studied. For all stages of HI, the predicted PK parameters of drugs were within twofold of the observed data. This successful validation increases confidence in using the DMET abundance data in HI to predict the changes in the PK of drugs cleared by DMET for which phenotyping studies in HI are not available or cannot be conducted. In addition, using CYP3A drugs as an example, through simulations, we identified the salient PK factors that drive the major changes in exposure (area under the plasma concentration-time profile curve) to drugs in HI. This theoretical framework can be applied to any drug and DMET to quickly determine the likely magnitude of change in drug PK due to HI.

Impairment of cardiovascular control is common in multiple sclerosis (MS), possibly due to damage of strategic brain regions such as the insula. Aerobic training (AT) targets cardiopulmonary system and may represent a neuroprotective strategy.To investigate whether insular damage (T2-hyperintense lesions and volume) is associated with cardiovascular fitness (CF) and influences AT effects in MS.Sixty-one MS patients were randomized to an AT intervention group (MS-AT) and a motor training control group (MS-C). At baseline and after training (24 sessions over 2-3 months), peak of oxygen consumption (VO2max), heart rate reserve (HRR), 6-min walk test (6MWT) and whole brain and insula MRI data were collected. Two healthy control (HC) groups were enrolled for CF and MRI data analysis.At baseline, MS patients vs HC showed impaired VO2max, HRR and 6MWT (p 0.001) and widespread gray matter atrophy, including bilateral insula. In MS patients, left insula T2-lesion volume correlated with HRR (r = 0.27, p = 0.042). After training, MS-AT, especially those without insular T2-hyperintense lesions, showed 6MWT improvement (p 0.05) and a stable insular volume, whereas MS-C showed left insular volume loss (p 0.001).By increasing 6MWT performance, our results suggest that AT may improve walking capacity and submaximal measure of CF in MS patients. Such beneficial effect may be modulated by insula integrity.

The Italian Neuroimaging Network Initiative (INNI) is an expanding repository of brain MRI data from multiple sclerosis (MS) patients recruited at four Italian MRI research sites. We describe the raw data quality of resting-state functional MRI (RS-fMRI) time-series in INNI and the inter-site variability in functional connectivity (FC) features after unified automated data preprocessing. MRI datasets from 489 MS patients and 246 healthy control (HC) subjects were retrieved from the INNI database. Raw data quality metrics included temporal signal-to-noise ratio (tSNR), spatial smoothness (FWHM), framewise displacement (FD), and differential variation in signals (DVARS). Automated preprocessing integrated white-matter lesion segmentation (SAMSEG) into a standard fMRI pipeline (fMRIPrep). FC features were calculated on pre-processed data and harmonized between sites (Combat) prior to assessing general MS-related alterations. Across centers (both groups), median tSNR and FWHM ranged from 47 to 84 and from 2.0 to 2.5, and median FD and DVARS ranged from 0.08 to 0.24 and from 1.06 to 1.22. After preprocessing, only global FC-related features were significantly correlated with FD or DVARS. Across large-scale networks, age/sex/FD-adjusted and harmonized FC features exhibited both inter-site and site-specific inter-group effects. Significant general reductions were obtained for somatomotor and limbic networks in MS patients (vs. HC). The implemented procedures provide technical information on raw data quality and outcome of fully automated preprocessing that might serve as reference in future RS-fMRI studies within INNI. The unified pipeline introduced little bias across sites and appears suitable for multisite FC analyses on harmonized network estimates.

Background: Previous studies demonstrated an association between motor and cognitive performance in multiple sclerosis (MS). However, disease-related brain damage might represent a common substrate to both phenomena, which was not considered before. Objective: Aim of this study is to investigate whether the association between cognition and motor function is beyond structural damage in patients with MS. Methods: Eighty-one healthy controls and 106 relapsing–remitting (RR) MS patients underwent a 3.0T MRI with quantification of T2-lesion volumes, T1-lesion volumes and normalized brain volumes. A functional examination [Nine-Hole Peg Test (9-HPT), Timed 25-Foot Walk test (T25FW) and Expanded Disability Status Scale] and a neuropsychological evaluation (Brief Repeatable Battery of Neuropsychological Tests) were also administered. Association between demographic, clinical, cognitive, MRI and functional measures were analysed with univariate analyses and hierarchical linear regression. Results: In RRMS patients, Spatial Recall Test and Symbol Digit Modalities Test were positively correlated with 9-HPT (p < 0.001) and T25FW (p ≤ 0.035); Paced Auditory Serial Addition Test (PASAT) correlated with 9-HPT (p ≤ 0.009). 9-HPT and T25FW were significantly associated with normalized brain volumes (p ≤ 0.016), T2- and T1-lesion volumes (p ≤ 0.009). Hierarchical regression models selected age and normalized deep gray matter volume as predictors of T25FW (adjusted-R2 = 0.109). Younger age, female sex, higher normalized gray matter volume and higher PASAT 2″ scores predicted higher 9-HPT scores (adjusted-R2 = 0.337). Conclusions: In RRMS patients, deficit in information processing speed and executive function may contribute to hand motor dysfunction beyond the effect of structural disease-related burden, supporting the integration of motor and cognitive assessment in clinical settings.

Aim: The conometric concept was proposed as a possible connection between the abutment and the prosthetic coping. This research aimed to review the features and possible clinical uses of this connection in an implant-supported fixed prosthesis. Methods: An electronic search was conducted on an online database for the topic in object; articles published in international literature were considered and the research gave 17 results, and 6 parameters were analyzed. Results: This connection eliminated the possibility of cement residues in the subgingival region, reducing the risk of inflammation of peri-implant soft and hard tissues; not having to remove the cement residues, it is possible to place the margins in more apical portions, improving the aesthetics outcomes of the rehabilitations. It is also known that the retention by means of a screw causes a weakening of the restoration. The retentive force is adequate for fixed rehabilitation even after a high number of insertion–disengagement cycles; in vitro studies have also shown a high bacterial sealing. Implant rehabilitation using preformed components, such as conometric hoods, is helpful for CAD/CAM, so a digital workflow is possible. Several types of prosthesis were presented, all of which demonstrated adequate clinical performance in the follow-up observation. Conclusions: This type of connection seems to be suitable to support fixed implant rehabilitations, but long-term clinical studies are needed to validate this system.

Introduction and objectives Quantification of cardiovascular risk has been based on scores such as Framingham, Framingham-REGICOR, SCORE or Life's Simple 7 (LS7). In vitro, animal, and randomized clinical studies have shown that polyphenols may provide benefits to the vascular system and reduce the inflammatory response. However, some clinical-epidemiological studies have yielded inconsistent results. Our aim was to assess the possible association between intake of the various polyphenol classes and established cardiovascular scores. Methods This cross-sectional analysis involved 6633 PREDIMED-Plus study participants. Food polyphenol content was estimated by a semiquantitative food frequency questionnaire , adjusted for total energy intake according to the residual method. The association between polyphenol intake and cardiovascular risk was tested using linear regression analyses. Results Total polyphenol and flavonoid intake were directly and significantly associated only with the LS7 scale. Intake of lignans was directly and significantly associated with SCORE and LS7 scales, stilbene intake with SCORE, and phenolic acid intake with Framingham and Framingham-REGICOR scores. Other polyphenol classes were associated in a protective and significant manner in Framingham, SCORE and LS7 scores. In women, intake of all the polyphenol classes, except phenolic acids, showed a protective trend in the results of the Framingham, Framingham-REGICOR scores and LS7 scale. Conclusions An inverse association was found between consumption of the ‘other polyphenols’ class and, especially among women, with estimated cardiovascular risk. The results were similar to those of Framingham, Framingham-REGICOR and LS7 (after eliminating the diet component) and differed from those of SCORE, but the predictors included were limited in the latter case.

Background and purpose: To investigate the relationship between the functional connectivity (FC) of the sensorimotor and cognitive cerebellum and measures of structural damage in patients with multiple sclerosis (MS) and no physical disability. Methods: We selected 144 relapsing-remitting MS patients with an Expanded Disability Status Scale score of ≤1.5 and 98 healthy controls from the Italian Neuroimaging Network Initiative database. From multimodal 3T magnetic resonance imaging (MRI), including functional MRI at rest, we calculated lesion load, cortical thickness, and white matter, cortical gray matter, and caudate, putamen, thalamic, and cerebellar volumes. Voxel-wise FC of the sensorimotor and cognitive cerebellum was assessed with seed-based analysis, and multiple regression analysis was used to evaluate the relationship between FC and structural damage. Results: Whole brain, white matter, caudate, putamen, and thalamic volumes were reduced in patients compared to controls, whereas cortical gray matter was not significantly different in patients versus controls. Both the sensorimotor and cognitive cerebellum showed a widespread pattern of increased and decreased FC that were negatively associated with structural measures, indicating that the lower the FC, the greater the tissue loss. Lastly, among multiple structural measures, cortical gray matter and white matter volumes were the best predictors of cerebellar FC alterations. Conclusions: Increased and decreased cerebellar FC with several brain areas coexist in MS patients with no disability. Our data suggest that white matter loss hampers FC, whereas, in the absence of atrophy, cortical volume represents the framework for FC to increase.

Plasma proteins or human serum albumin (HSA) have been reported to increase the in vitro intrinsic uptake clearance (CL

OBJECTIVES The aims of this study were to present a deep learning approach for the automated classification of multiple sclerosis and its mimics and compare model performance with that of 2 expert neuroradiologists. MATERIALS AND METHODS A total of 268 T2-weighted and T1-weighted brain magnetic resonance imagin scans were retrospectively collected from patients with migraine (n = 56), multiple sclerosis (n = 70), neuromyelitis optica spectrum disorders (n = 91), and central nervous system vasculitis (n = 51). The neural network architecture, trained on 178 scans, was based on a cascade of 4 three-dimensional convolutional layers, followed by a fully dense layer after feature extraction. The ability of the final algorithm to correctly classify the diseases in an independent test set of 90 scans was compared with that of the neuroradiologists. RESULTS The interrater agreement was 84.9% (Cohen κ = 0.78, P < 0.001). In the test set, deep learning and expert raters reached the highest diagnostic accuracy in multiple sclerosis (98.8% vs 72.8%, P < 0.001, for rater 1; and 81.8%, P < 0.001, for rater 2) and the lowest in neuromyelitis optica spectrum disorders (88.6% vs 4.4%, P < 0.001, for both raters), whereas they achieved intermediate values for migraine (92.2% vs 53%, P = 0.03, for rater 1; and 64.8%, P = 0.01, for rater 2) and vasculitis (92.1% vs 54.6%, P = 0.3, for rater 1; and 45.5%, P = 0.2, for rater 2). The overall performance of the automated method exceeded that of expert raters, with the worst misdiagnosis when discriminating between neuromyelitis optica spectrum disorders and vasculitis or migraine. CONCLUSIONS A neural network performed better than expert raters in terms of accuracy in classifying white matter disorders from magnetic resonance imaging and may help in their diagnostic work-up.

Background: The pathogenetic mechanisms sustaining neuroinflammatory disorders may originate from the cerebrospinal fluid. Objective: To evaluate white matter damage with diffusion tensor imaging and T1/T2-weighted ratio at progressive distances from the ventricular system in neuromyelitis optica spectrum disorders and multiple sclerosis. Methods: Fractional anisotropy, mean, axial, and radial diffusivity and T1/T2-weighted ratio maps were obtained from patients with seropositive neuromyelitis optica spectrum disorders, multiple sclerosis, and healthy controls ( n = 20 each group). White matter damage was assessed as function of ventricular distance within progressive concentric bands. Results: Compared to healthy controls, neuromyelitis optica spectrum disorders patients had similar fractional anisotropy, radial and axial diffusivity, increased mean diffusivity ( p = 0.009–0.013) and reduced T1/T2-weighted ratio ( p = 0.024–0.037) in all bands. In multiple sclerosis, gradient of percentage lesion volume and intra-lesional mean and axial diffusivity were higher in periventricular bands. Compared to healthy controls, multiple sclerosis patients had reduced fractional anisotropy ( p = 0.001–0.043) in periventricular bands, increased mean ( p Conclusion: White matter damage is higher at periventricular level in multiple sclerosis and diffuse in neuromyelitis optica spectrum disorders. Fractional anisotropy preservation, associated with increased mean diffusivity and reduced T1/T2-weighted ratio may reflect astrocyte damage.

This study provides information on the potential human health risk of Hg, Cd, Pb and As exposure from consumption of two fish species (Umbrina cirrosa and Sciaena umbra) in the general population and in high-level fish consumers. The concentrations did not show significant differences between the two species, and no fish length element level–body-length relationship was observed, except for Hg. The average metal(loid) levels, irrespective of species, varied in the following ranges: Hg = 0.18–0.19, Cd = 0.07–0.10, Pb = 0.10–0.12, As = 0.59–0.69 μg g−1 w.w. The concentrations remained below the maximum permissible limits (MPLs) for human consumption, except for Cd. The estimated intakes of Hg, Cd and Pb in both consumption scenarios were lower than the respective PTWI/PTMIs, as well as those of inorganic As, which were even lower than the BMDL01. The non-carcinogenic risk (THQ) did not reveal any concerns, except for Hg. The lifetime health cancer risk (ILCR) suggested hazard exclusively from Cd, although for high-level fish consumers, even the ILCR of inorganic As was, in some cases, above the acceptable range. Continuous monitoring of metal(loid) levels in these fish is strongly recommended because the results demonstrate the occurrence of potential health risks, especially in high-level fish consumers, due to the presence of Hg and Cd.

We studied whether professional traders’ risk attitudes varied according to social context. To this extent, we examined whether the level of wealth in the relevant group influenced traders’ risky decisions. The results showed that risk aversion decreased with increased income/wealth conditions in the group context.

BACKGROUND: Dietary polyphenol intake has been associated with a decreased risk of hyperuricemia, but most of this knowledge comes from preclinical studies. The aim of the present study was to assess the association of the intake of different classes of polyphenols with serum uric acid and hyperuricemia. METHODS AND RESULTS: This cross-sectional analysis involved baseline data of 6332 participants. Food polyphenol content was estimated by a validated semiquantitative food frequency questionnaire and from the Phenol-Explorer database. Multivariable-adjusted linear regression models with serum uric acid (milligrams per deciliter) as the outcome and polyphenol intake (quintiles) as the main independent variable were fitted. Cox regression models with constant follow-up time (t=1) were performed to estimate the prevalence ratios (PRs) of hyperuricemia (≥7 mg/dL in men and ≥6 mg/dL in women). An inverse association between the intake of the phenolic acid class (β coefficient, −0.17 mg/dL for quintile 5 versus quintile 1 [95% CI, −0.27 to −0.06]) and hydroxycinnamic acids (β coefficient, −0.19 [95% CI, −0.3 to −0.09]), alkylmethoxyphenols (β coefficient, −0.2 [95% CI, −0.31 to −0.1]), and methoxyphenols (β coefficient, −0.24 [95% CI, −0.34 to −0.13]) subclasses with serum uric acid levels and hyperuricemia (PR, 0.82 [95% CI, 0.71–0.95]; PR, 0.82 [95% CI, 0.71–0.95]; PR, 0.80 [95% CI, 0.70–0.92]; and PR, 0.79 [95% CI, 0.69–0.91]; respectively) was found. The intake of hydroxybenzoic acids was directly and significantly associated with mean serum uric acid levels (β coefficient, 0.14 for quintile 5 versus quintile 1 [95% CI, 0.02–0.26]) but not with hyperuricemia. CONCLUSIONS: In individuals with metabolic syndrome, a higher intake of some polyphenol subclasses (hydroxycinnamic acids, alkylmethoxyphenol, and methoxyphenol) was inversely associated with serum uric acid levels and hyperuricemia. Nevertheless, our findings warrant further research., European Research Council (ERC) European Commission 2013-2018 340918, official funding agency for biomedical research of the Spanish government Instituto de Salud Carlos III, European Commission PI13/00673 PI13/00492 PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/02184 PI13/00728 PI13/01090 PI13/01056 PI14/01722 PI14/00636 PI14/00618 PI14/00696 PI14/01206 PI14/01919, Especial Action Project, La Caixa Foundation 2013ACUP00194, Consejo Interinstitucional de Ciencia y Tecnologia (CICYT) AGL2016-75329-R, Center for Forestry Research & Experimentation (CIEF), European Commission PROMETEO/2017/017, Generalitat de Catalunya SGR-2019, Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018, SEMERGEN (Sociedad Espanola de Medicos de Atencion Primaria), European Cooperation in Science and Technology (COST), IDISBA (Instituto de Investigacion Sanitaria Islas Baleares), European Commission CIBEROBN CB06/03 CB12/03, European Commission European Commission Joint Research Centre EAT2BENI-CE_H2020_SFS2016, Spanish Ministry of Science, Innovation and Universities for the Formacion de Profesorado Universitario FPU17/00785, Instituto de Salud Carlos III, through the Fondo de Investigacion para la Salud - European Regional Development Fund PI16/00501 PI16/00533 PI16/00381 PI16/00366 PI16/01522 PI16/01120 PI17/00764 PI17/01183 PI17/00855 PI17/01347 PI17/00525 PI17/01827 PI17/00532 PI17/00215 PI17/01441 PI17/00508 PI17/01732 PI17/00926 PI19/00957 PI16/00473, Instituto de Salud Carlos III European Commission PI14/00853 PI14/01374 PI14/00972 PI19/00386 PI19/00309 PI19/01032 PI19/00576 PI19/00017 PI19/01226 PI19/00781 PI19/01560 PI16/00662 PI16/01873 PI16/01094 PI19/01332 PI14/00728 PI14/01471

Objectives: Magnetic resonance imaging (MRI) is an important tool for diagnosis and monitoring of disease course in multiple sclerosis (MS). However, its prognostic value for predicting disease worsening is still being debated. The aim of this study was to propose a deep learning algorithm to predict disease worsening at 2 years of follow-up on a multicenter cohort of MS patients collected from the Italian Neuroimaging Network Initiative using baseline MRI, and compare it with 2 expert physicians. Materials and methods: For 373 MS patients, baseline T2-weighted and T1-weighted brain MRI scans, as well as baseline and 2-year clinical and cognitive assessments, were collected from the Italian Neuroimaging Network Initiative repository. A deep learning architecture based on convolutional neural networks was implemented to predict: (1) clinical worsening (Expanded Disability Status Scale [EDSS]-based model), (2) cognitive deterioration (Symbol Digit Modalities Test [SDMT]-based model), or (3) both (EDSS + SDMT-based model). The method was tested on an independent data set and compared with the performance of 2 expert physicians. Results: For the test set, the convolutional neural network model showed high predictive accuracy for clinical (83.3%) and cognitive (67.7%) worsening, although the highest accuracy was reached when training the algorithm using both EDSS and SDMT information (85.7%). Artificial intelligence classification performance exceeded that of 2 expert physicians (70% of accuracy for the human raters). Conclusions: We developed a robust and accurate model for predicting clinical and cognitive worsening of MS patients after 2 years, based on conventional T2-weighted and T1-weighted brain MRI scans obtained at baseline. This algorithm may be valuable for supporting physicians in their clinical practice for the earlier identification of MS patients at risk of disease worsening.

Numerous evidence and clinical trials have been published in recent years on the role of silicon for the maintenance of general well-being and of bones in particular. However, no study has so far investigated which fundamental contribution to health could provide silicon when taken with other trace elements in cases, very frequent, of their insufficient contribution. In this work we present a preliminary open-air study on a group of patients, using an original and innovative formulation containing organic SI G5 plus other trace elements, for the prevention and treatment of osteoarticular diseases of various origins.

Ditylenchus dipsaci is an economically important plant-parasitic nematode affecting European sugar beets. To date, no sugar beet cultivars carrying resistance against D. dipsaci are available to farmers. To find potentially resistant sugar beet lines restricting reproduction and penetration of D. dipsaci, three consecutive in vivo bioassays were carried out. The first experiment determined the penetration rate of D. dipsaci in 79 breeding lines and 14 pre-breeding populations. Based on these results, D. dipsaci penetration and reproduction resistance of eight genotypes was intensively investigated. It could be demonstrated that none of the genotypes showed resistance towards D. dipsaci. However, a high variation of the penetration rate by D. dipsaci was observed among the genotypes. The breeding line ‘DIT_119’ effectively reduced D. dipsaci penetration (34.4 ± 8.8 nematodes/plant at 22 days post-planting) compared to the susceptible control (109.0 ± 16.9) while ensuring a yield comparable to non-inoculated plants. However, the breeding line ‘DIT_119’ did not reduce D. dipsaci reproduction. The paternal line of the cultivar BERETTA KWS, demonstrating a high tolerance to D. dipsaci crown rot symptoms, did not reduce penetration and reproduction. Thus, no correlation can be established between reduced penetration rates, reproduction, and tolerance to D. dipsaci. This study provides an essential basis for the development of resistant sugar beet cultivars to D. dipsaci. The variations observed among genotypes now need to be confirmed with larger-scale screenings.

The stem nematode, Ditylenchus dipsaci, is a severe pest in European sugar beet production. In France, Germany, and Switzerland, D. dipsaci damage in sugar beet varies among specific geographic areas. In this study, the reproduction potential of four geographically distinct D. dipsaci populations was determined using sterile carrot disc cultures. In addition, virulence and pathogenicity were investigated in-vivo using sugar beet. No difference was found in the reproduction potential on carrot discs, as well as penetration rate in sugar beet seedlings. The reproduction rate in sugar beet tissue was significantly affected by the D. dipsaci population used. The population from Seeland (CH) showed the highest number of nematodes per plant at 60 dpi (21,071.8 ± 5340.0), compared to the three other populations contained 3588.6 ± 3858.3, 5136.9 ± 4950.8, and 3579.7 ± 5174.2, respectively. Furthermore, the reproduction rate of D. dipsaci was negatively correlated with fresh biomass of sugar beets at 60 dpi. Based on these results, the D. dipsaci population “Seeland” is suitable for breeding programs to detect resistance in sugar beet. After selecting candidate genotypes/varieties, these should be further evaluated for their field resistance in their targeted growing regions.

Purpose: Determine the time-dependent magnitude of intrafraction prostate displacement and a cutoff for the tracking decision. Methods: Nine patients with localized prostate cancer were treated with ultra-hypofractionated radiotherapy (CyberKnife) with fiducial markers. Exact tract kV/kV imaging was used with an average interval of 19–92 s. A Gaussian distribution was calculated for the x-, y-, and z-directions (σx,y,z). The variation of prostate motion (μσ) was obtained by averaging the patients’ specifics, and the safety margin was calculated to be MAB = WYm + WBSs. Results: The calculated PTV safety margins were as follows: at 40 s: 0.55 mm (L/r), 0.85 mm (a/p), and 1.05 mm (s/i); at 60 s: 0.9 mm (L/r), 1.35 mm (a/p), and 1.55 mm (s/i); at 100 s: 1.5 mm (L/r), 2.3 mm (a/p), and 2.6 mm (s/i); at 150 s: 1.9 mm (L/r), 3.1 mm (a/p), and 3.6 mm (s/i); at 200 s: 2.2 mm (L/r), 3.8 mm (a/p), and 4.2 mm (s/i); and at 300 s: 2.6 mm (L/r), 5.3 mm (a/p), and 5.6 mm (s/i). A tracking cutoff of 2.5 min seemed reasonable. In order to achieve an accuracy of < 1 mm, tracking with < 50 s intervals was necessary. Conclusions: For ultra-hypofractionated radiotherapy of the prostate with treatment times > 2.5 min, intrafraction motion management is recommended.

Dietary intake of polychlorinated dioxins and furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) from various foods (fish and seafood, meat and meat-based products, milk and dairy products, hen eggs, olive oil and fats) was investigated for various sex/age groups of the Italian population. The concentrations of PCDD/Fs and dl-PCBs and their contribution to total TEQ values varied depending on food matrix. Fish (0.50 pg WHO-TEQ/g wet weight) and seafood (0.16 pg WHO-TEQ/g wet weight) showed the highest mean concentrations of PCDD/Fs plus dl-PCBs, followed by meat (1.70 pg WHO-TEQ/g lipid weight), meat based products (1.03 pg WHO-TEQ/g lipid weight), milk and dairy products (0.78 pg WHO-TEQ/g lipid weight), hen eggs (0.71 pg WHO-TEQ/g lipid weight), fats (0.27 pg WHO-TEQ/g lipid weight) and olive oil (0.09 pg WHO-TEQ/g lipid weight). In all samples WHO-TEQ PCDD/F plus dl-PCB concentrations fulfilled the European Union food law, except in pork loin samples (1.39 pg WHO-TEQ/g lipid weight). Differences in exposure depending on the sex/age groups (children > teenagers > adults > elders) and hypotheses considered (lower bound and upper bound) were encountered. Non-cancer risk values showed a low exposure. Carcinogenicity risk results revealed that highly exposed individuals were distributed over all sex/age groups, even though the proportion of individuals exceeding the safe limit was higher in children. These data once again underline the importance of trying to control the levels of these contaminants in fishery products, particularly in fish, who represents one of the main exposure sources for consumers. PRACTICAL APPLICATION: This paper may help the consumer in making food choices to minimize the exposure risk to dioxins, furans and PCBs.

Summary The stem nematode, Ditylenchus dipsaci, causes severe damage in sugar beet. To date, nematode inoculation through the leaf axil has been used as the standard method to investigate D. dipsaci interaction with sugar beet under in vivo conditions. To get as close as possible to field conditions, we established a new screening mechanism to perform soil inoculation. The most suitable inoculation time point, inoculum level and positioning on sugar beet, as well as rearing process on carrots, were determined. At a 15:8°C day:night temperature regime, penetration rates of D. dipsaci were at maximum following soil inoculation at plant emergence. Up to 115 nematodes penetrated sugar beet seedlings 22 days post-planting with an inoculum level of 1000 nematodes into the soil at plant emergence. Ditylenchus dipsaci penetration rate was higher in plants with soil inoculation than with inoculation on to the leaf axil. High soil moisture increased nematode migration into seedlings when D. dipsaci inoculation was carried out in four holes 1 cm from the plant base. Rearing the nematodes for 35 days at 20°C on carrot discs resulted in an infective inoculum containing up to 50% eggs. We recommend a soil inoculation of 1000 freshly extracted nematodes per pot at plant emergence. The nematode suspension has to be previously reared for 35 days on carrot discs to obtain active D. dipsaci inoculum. This system will allow for the selection of suitable sugar beet genotypes that suppress nematode penetration, in support of breeding for resistance against D. dipsaci.

Objetivo: Valorar el efecto de una intervención nutricional intensiva, basada en la aplicación de una dieta mediterránea hipocalórica personalizada, sobre el peso corporal y el perímetro de la cintura en adultos refractarios a la pérdida de peso. Material y métodos: Se realizó un estudio prospectivo durante 6 meses en 100 participantes con edades comprendidas entre 55-75 años, índice de masa corporal ≥ 27 y < 40 kg/m2, que cumplieran con 3 o más criterios de síndrome metabólico. La intervención consistió en la pauta de una dieta mediterránea hipocalórica, recomendaciones de ejercicio y entrevistas motivacionales. Se recogieron variables antropométricas una vez al mes durante toda la intervención. Para analizar los resultados se realizaron los test de la chi al cuadrado y t de Student, y se calculó mediante regresión logística no condicional los odds ratio con intervalos de confianza del 95% de las variables asociadas a la pérdida de peso. Resultados: Tras la intervención de «rescate», los pacientes perdieron una media del 2,9% del peso corporal y del 2,1% del perímetro abdominal, alcanzando el 38% de la muestra una pérdida ≥ 3% del peso y el 26% de la muestra una reducción ≥ 3% de circunferencia de cintura. No se observaron diferencias estadísticamente significativas en la pérdida de peso y cintura en ninguna de las variables analizadas. Conclusiones: Una intervención intensiva, basada en una dieta mediterránea hipocalórica, recomendación de actividad física y charlas motivacionales, consigue pérdidas moderadas de peso en pacientes refractarios a los tratamientos contra la obesidad. Objective: To assess the effect of an intensive nutritional intervention on the body weight and waist circumference in adults refractory to weight loss, by applying a personalised low-calorie Mediterranean diet. Material and methods: A prospective study was conducted for 6 months on 100 participants with an age range between 55 and 75 years, a BMI ≥ 27 and < 40 kg/my, and fulfilled 3 or more criteria of metabolic syndrome. The intervention consisted of prescribing a low-calorie Mediterranean diet, exercise recommendations, and motivational talks. Anthropometric variables were recorded 11a month during the entire intervention. An analysis was made of the results using the Chi-squared and Student-t tests. The Odds Ratio of the variables associated with weight loss and their 95% confidence intervals was calculated using a non-conditional logistic regression. Results: After the "rescue" intervention, the patients lost an average of 2.9% of the body weight and 2.1% of waist circumference, the target of the loss ≥ 3% of the weight and 26% of the sample the target of reduction ≥ 3% of waist circumference being achieved 38% of the sample. No statistically significant differences were observed in weight and waist circumference loss in any of the variables analysed. Conclusions: Intensive intervention, based on a low-calorie Mediterranean diet, with recommendations of physical activity and motivational talks, achieved a moderate weight loss in patients refractory to treatments for obesity.

Research misconduct (RM) is an alarming concern worldwide, and especially in Italy, where there is no formal training of young researchers in responsible research practices. The main aim of this study was to map the perceptions and attitudes about RM in a sample of young researchers attending a one-week intensive course on methodology, ethics and integrity in biomedical research, held at the University of Insubria (Italy). To this end, we administered the Scientific Misconduct Questionnaire (SMQ-R) to all attendees at the beginning of the course. Thereafter, SMQ-R was re-administered at the end, to assess the impact of the course on the responsiveness of study participants, which is intended as the frequency of responses other than “don’t know”. Results show that respondents rate as high their own understanding about rules and procedures related to scientific misconduct (49.2% of respondents), as well as the effectiveness of their institution’s measures for reducing it (40%). Most of them (44.6%) perceive as low the chances of getting caught for RM. Some respondents believe that cases of misconduct occur in their workplace (20%–46.2%) and that the integrity of a research is not solely the responsibility of the principal investigator (73.8%). Among the main factors contributing to research misconduct, the need for publications, unclear definition of what constitutes misconduct and pressure for external funding do stand out. Respondents are concerned about the amount of misconduct and express a pressing need for training on research ethics. Remarkably, the responsiveness of participants tends to increase with course attendance. This finding may be useful to support education programmes devoted to research methodology, ethics and integrity among young researchers.

The stem and bulb nematode Ditylenchus dipsaci (Kuhn 1857) Filipjev 1936 is a migratory endoparasite ranked in the top ten plant-parasitic nematodes worldwide. Ditylenchus dipsaci has emerged as an economically threatening pest in the European sugar beet (Beta vulgaris L.) production. In Germany and Switzerland, some major sugar beet growing regions are particularly affected by D. dipsaci. The nematode migrates into the plant in the spring and reproduces in the hypocotyl during the growing season. Soil-borne pathogens introduced by D. dipsaci leads to crown root rotting and plant death. The broad range of host plants of D. dipsaci hinders crop rotation strategies for a successful management of this nematode. To date, no sugar beet cultivars carrying resistance towards D. dipsaci are available for sugar beet producers, depriving them of effective measures against this nematode. The lack of control measures and the growing public demand for sustainable sugar production have encouraged breeders to develop resistant cultivars. For this reason, this thesis aimed to investigate resistance against D. dipsaci on sugar beet. Before investigating the interaction between sugar beet and the nematode, the development of an in vivo test system was required. It aimed to replace above-ground D. dipsaci inoculation with a soil inoculation more closely related to field conditions. The most suitable inoculation time point, inoculum level, and positioning on sugar beets, as well as rearing process on carrots, were determined. At a 15:8°C day:night temperature regime, penetration rates of D. dipsaci into sugar beet seedlings were at maximum following soil inoculation at plant emergence. High soil moisture increased nematode migration into seedlings when D. dipsaci inoculation was carried out in four holes 1 cm from the plant base. The nematode suspension was previously reared for 35 days on carrot discs to obtain active D. dipsaci inoculum. To find potentially resistant sugar beet restricting reproduction and penetration of D. dipsaci, in vivo bioassays were carried out with 15 pre‑breeding populations and 79 breeding lines. It could be demonstrated that none of the genotypes showed complete resistance towards D. dipsaci. However, a high variation of the penetration rate by D. dipsaci was observed among the genotypes. They also responded differently to the fresh biomass reduction caused by the nematode combined with soil-borne pathogens. Based on these results, candidates for partial resistance were further investigated in microplot experiments conducted in the Rhineland (DE) and Seeland (CH) regions. The sugar beet genotype effect on D. dipsaci penetration could not be validated. The genotypes did not show a sufficient tolerance towards the rotting of the plant tissue. Nematode pathogenicity and virulence differed depending on experiment locations and years. Finally, virulence and pathogenicity of four D. dipsaci populations were investigated under in vivo conditions. No difference was found in D. dipsaci penetration rate into sugar beet seedlings. However, Seeland (CH) population showed a significantly higher reproduction on sugar beets than the others populations, validating observations obtained in microplot experiments.

Total mercury (THg), methylmercury (MeHg), and selenium (Se) concentrations were measured in various commercially important fish species. The benefit–risk binomial associated with these chemicals was assessed in children through the probability of exceeding the provisional tolerable weekly intakes (PTWIs) of the contaminants and the Se recommended dietary allowance (RDA). The Se:Hg molar ratios, selenium health benefit values (HBVSe), and monthly consumption rate limits (CRmm) for each species were also calculated. THg and Se were analyzed by atomic absorption spectrophotometer (Shimadzu, Milan, Italy), while MeHg was determined by Trace Ultra gas chromatograph connected with a PolarisQ MS (Thermo Fisher Scientific, Waltham, MA, USA). None of the analyzed fish had Hg levels above the European Community regulatory limits, while most large predators had MeHg levels over the threshold concentration set by US EPA. The estimated weekly intakes of THg and MeHg exceeded in many cases the PTWIs and the Se estimated daily intakes were provided from 0.71% to 2.75% of the RDA. Se:Hg molar ratios above 1 and positive HBVSe index suggested that Se in fish could be enough to alleviate the potential toxic effect of Hg. However, high-risk groups as children should consume fish in moderation because a large consumption pattern, especially of swordfish and tunas, might be of concern for health.

White matter (WM) atrophy is relevant in multiple sclerosis (MS), but the methods of analysis currently used are not specific for microstructural changes. The aims of this study were to assess the use of advanced diffusion-weighted imaging (DWI) techniques proposed as measures of baseline and longitudinal WM atrophy in MS and to analyze whether these measures helped explain MS clinical disability (including cognitive impairment) better than volumetric and diffusion tensor (DT)-derived measures.3DT1-weighted and DWI sequences were applied to 86 MS and 55 healthy controls (HC) at baseline and after one-year. Intra-cellular volume (vBoth at baseline and after 1-year, only FCS measure showed a significant atrophy in relapsing-remitting (RR) MS compared to HC and in progressive MS compared to RRMS, mainly located in specific WM tracts (corticospinal tract, splenium of the corpus callosum, left optic radiation, bilateral cingulum, middle cerebellar peduncle and anterior commissure, p value 0.05). Global baseline FCS and vVoxel-based FCS was able to detect WM tracts atrophy in MS clinical phenotypes with greater anatomical specificity compared to other measures (volumetric and DT-derived measures of WM damage). FCS and v

To assess efficacy and toxicity of a drug in humans, it is important to measure the tissue concentration of a drug at the target site. For a drug that is transported into or out of the tissue, the tissue unbound steady-state concentration can be dramatically different from its corresponding unbound steady-state plasma concentration. Because routine measurement of drug tissue concentrations is not possible, using rosuvastatin as a model transporter substrate drug, we compared the ability of the proteomics-informed relative expression factor (REF) approach and sandwich-cultured human hepatocytes (SCH) to accurately predict rosuvastatin human hepatobiliary clearances and hepatic concentrations. REF-predicted rosuvastatin biliary clearance (CL

The role of uric acid levels in the cardiovascular continuum is not clear. Our objective is to analyze the prevalence of hyperuricemia (HU) and its association with cardiovascular risk factors (CVRF), subclinical target organ damage (sTOD), and cardiovascular diseases (CVD). We evaluated the prevalence of HU in 6.927 patients included in the baseline visit of the IBERICAN study. HU was defined as uric acid levels above 6 mg/dL in women, and 7 mg/dL in men. Using adjusted logistic regression models, the odds ratios were estimated according to CVRF, sTOD, and CVD. The prevalence of HU was 16.3%. The risk of HU was higher in patients with pathological glomerular filtration rate (aOR: 2.92), heart failure (HF) (aOR: 1.91), abdominal obesity (aOR: 1.80), hypertension (HTN) (aOR: 1.65), use of thiazides (aOR: 1.54), left ventricular hypertrophy (LVH) (aOR: 1.36), atrial fibrillation (AFIB) (aOR: 1.29), and albuminuria (aOR: 1.27). On the other hand, being female (aOR: 0.82) showed a reduced risk. The prevalence of HU was higher in men, in patients presenting CVRF such as HTN and abdominal obesity, and with co-existence of LVH, atrial fibrillation (AFIB), HF, and any form of kidney injury. These associations raise the possibility that HU forms part of the early stages of the cardiovascular continuum. This may influence its management in Primary Healthcare because the presence of HU could mean an increased CV risk in the patients.

Although there is a clear relationship between family history (FH) and the risk of gastric cancer (GC), quantification is still needed in relation to different histological types and anatomical sites, and in strata of covariates. The objective was to analyze the risk of GC according to first-degree FH in a uniquely large epidemiological consortium of GC. This investigation includes 5946 cases and 12,776 controls from 17 studies of the Stomach Cancer Pooling (StoP) Project consortium. Summary odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were calculated by pooling study-specific ORs using fixed-effect model meta-analysis techniques. Stratified analyses were carried out by sex, age, tumor location and histological type, smoking habit, socioeconomic status, alcohol intake and fruit consumption. The pooled OR for GC was 1.84 (95% CI: 1.64–2.04, I2 = 6.1%, P heterogeneity = 0.383) in subjects with vs. those without first-degree relatives with GC. No significant differences were observed among subgroups of sex, age, geographic area or study period. Associations tended to be stronger for non-cardia (OR = 1.82, 95% CI: 1.59–2.05 for subjects with FH) than for cardia GC (OR = 1.38, 95% CI: 0.98–1.77), and for the intestinal (OR = 1.92, 95% CI: 1.62–2.23) than for the diffuse histotype (OR = 1.62, 95% CI: 1.28–1.96). This analysis confirms the effect of FH on the risk of GC, reporting an approximately doubled risk, and provides further quantification of the risk of GC according to the subsite and histotype. Considering these findings, accounting for the presence of FH to carry out correct prevention and diagnosis measures is of the utmost importance.

This study provides valuable information on the levels of various trace metals (Pb, Cd, Hg, Zn, Cu, Cr) in meat products (baked ham, raw ham, mortadella, cured sausage, würstel, salami) from South Italy and calculates potential health risk toxicity associated with their consumption for the total population and for children. In the samples studied metal concentrations are within the permissible legal limits (Cd: 0.01–0.03 μg g−1 w.w., Hg: 0.01–0.02 μg g−1 w.w., Zn: 5.71–7.32 μg g−1 w.w., Cu: 1.08–1.21 μg g−1 w.w., Cr: 0.15–0.23 μg g−1 w.w.), except for Pb (Pb: 0.22–0.38 μg g−1 w.w.). The estimated intake values are within the provisional tolerable daily intake limits for toxic metals and recommended daily intake values for essential metals in both tested groups. The noncarcinogenic risk values of the individual metals indicate that there is no health risk, but their combined effects might constitute a potential risk for children. Furthermore, the cumulative cancer risk of all samples studied exceeds the recommended threshold risk limit (> 10−4) in both total population and children, indicating a risk of potential health problems for consumers especially for children, who are more vulnerable to toxic metal exposure.

Purpose To compare available methods for whole-brain and gray matter (GM) atrophy estimation in multiple sclerosis (MS) in terms of repeatability (same magnetic resonance [MR] imaging unit) and reproducibility (different system/field strength) for their potential clinical applications. Materials and Methods The softwares ANTs-v1.9, CIVET-v2.1, FSL-SIENAX/SIENA-5.0.1, Icometrix-MSmetrix-1.7, and SPM-v12 were compared. This retrospective study, performed between March 2015 and March 2017, collected data from (a) eight simulated MR images and longitudinal data (2 weeks) from 10 healthy control subjects to assess the cross-sectional and longitudinal accuracy of atrophy measures, (b) test-retest MR images in 29 patients with MS acquired within the same day at different imaging unit field strengths/manufacturers to evaluate precision, and (c) longitudinal data (1 year) in 24 patients with MS for the agreement between methods. Tissue segmentation, image registration, and white matter (WM) lesion filling were also evaluated. Multiple paired t tests were used for comparisons. Results High values of accuracy (0.87-0.97) for whole-brain and GM volumes were found, with the lowest values for MSmetrix. ANTs showed the lowest mean error (0.02%) for whole-brain atrophy in healthy control subjects, with a coefficient of variation of 0.5%. SPM showed the smallest mean error (0.07%) and coefficient of variation (0.08%) for GM atrophy. Globally, good repeatability (P > .05) but poor reproducibility (P < .05) were found for all methods. WM lesion filling technique mainly affected ANTs, MSmetrix, and SPM results (P < .05). Conclusion From this comparison, it would be possible to select a software for atrophy measurement, depending on the requirements of the application (research center, clinical trial) and its goal (accuracy and repeatability or reproducibility). An improved reproducibility is required for clinical application. © RSNA, 2018 Online supplemental material is available for this article.

Concentrations of some toxic (Hg, Cd, Pb) and essential metals (Zn, Cu, Cr, Fe) relevant to human health were determined in different varieties of traditional cheeses, included in Traditional Agricultural Food Products (TAP) list, sampled in various farms in Apulia and Sicily, two regions of Southern Italy. Among toxic metals, Pb showed the highest concentrations (hard cheese: 0.13 μg g−1 w.w.; fresh cheese: 0.07 μg g−1 w.w.), while among essential element the most abundant was Fe (hard cheese: 2.86 μg g−1 w.w.; fresh cheese: 2.23 μg g−1 w.w.). In terms of food safety, the toxic metal concentrations in the majority of the samples investigated were below the maximum permitted levels set by several non-European countries, except for Pb showing levels notably exceeding in some hard cheese (0.22–0.37 μg g−1 w.w.). Also the estimated intakes of toxic metals remained far below the provisional tolerable intakes and consequently no health risk is expected from the consumption of these cheeses. However, for greater food safety, besides to a continuous surveillance it would be advisable to establish maximum limits for metals either in milk or products made of milk.

Lake Cadagno, a permanently stratified high-alpine lake with a persistent microbial bloom in its anoxic chemocline, has long been considered a model for the low-oxygen, high-sulfide Proterozoic ocean where early microbial life gave rise to Earth’s oxygenated atmosphere. Although the lake has been studied for over 25 years, the absence of concerted study of the bacteria, phytoplankton, and viruses, together with primary and secondary production, has hindered a comprehensive understanding of its microbial food web. Here, the identities, abundances, and productivity of microbes were evaluated in the context of Lake Cadagno biogeochemistry. Photo-synthetic pigments and chloroplast 16S rRNA gene phylogenies suggested high abundances of eukaryotic phytoplankton, primarilyChlorophyta, through the water column. Of these, a close relative ofAnkyra judayi, a high-alpine adapted chlorophyte, peaked with oxygen in the mixolimnion, whileClosteriopsis-related chlorophytes peaked in the chemocline and monimolimnion. Anoxygenic phototrophic sulfur bacteria, Chromatium, dominated the chemocline along withLentimicrobium, a newly observed genus of known fermenters. Secondary production peaked in the chemocline, suggesting anoxygenic primary producers depended on heterotrophic nutrient remineralization. Virus-to-microbe ratios spanned an order of magnitude, peaking with high phytoplankton abundances and at a minimum at the peak of Chromatium, dynamic trends that suggest viruses may play a role in the modulation of oxygenic and anoxygenic photo- and chemosynthesis in Lake Cadagno. Through the combined analysis of bacterial, eukaryotic, viral, and biogeochemical dynamics of Lake Cadagno, this study provides a new perspective on the biological and geochemical connections that comprised the food webs of the Proterozoic ocean.IMPORTANCEAs a window to the past, the study offers insights into the role of microbial guilds of Proterozoic ocean chemoclines in the production and recycling of organic matter of sulfur- and ammonia-containing ancient oceans. The new observations described here suggest that eukaryotic algae were persistent in the low oxygen upper-chemocline in association with purple and green sulfur bacteria in the lower half of the chemocline. Further, this study provides the first insights into Lake Cadagno viral ecology. High viral abundances suggested viruses may be essential components of the chemocline where their activity may result in the release and recycling of organic matter. The framework developed in this study through the integration of diverse geochemical and biological data types lays the foundation for future studies to quantitatively resolve the processes performed by discrete populations comprising the microbial loop in this early anoxic ocean analogue.