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The first WHO guidelines for risk reduction of cognitive decline and dementia marked an important milestone in the field of dementia prevention. In this paper, we discuss the evidence reviewed as part of the guidelines development and present the main themes emerged from its synthesis, to inform future research and policies on dementia risk reduction. The role of intervention effect-size; the mismatch between observational and intervention-based evidence; the heterogeneity of evidence among intervention trials; the importance of intervention duration; the role of timing of exposure to a certain risk factor and interventions; the relationship between intervention intensity and response; the link between individual risk factors and specific dementia pathologies; and the need for tailored interventions emerged as the main themes. The interaction and clustering of individual risk factors, including genetics, was identified as the overarching theme. The evidence collected indicates that multidomain approaches targeting simultaneously multiple risk factors and tailored at both individual and population level, are likely to be most effective and feasible in dementia risk reduction. The current status of multidomain intervention trials aimed to cognitive impairment/dementia prevention was also briefly reviewed. Primary results were presented focusing on methodological differences and the potential of design harmonization for improving evidence quality. Since multidomain intervention trials address a condition with slow clinical manifestation-like dementia-in a relatively short time frame, the need for surrogate outcomes was also discussed, with a specific focus on the potential utility of dementia risk scores. Finally, we considered how multidomain intervention could be most effectively implemented in a public health context and the implications world-wide for other non-communicable diseases targeting common risk factors, taking into account the limited evidence in low-middle income countries. In conclusion, the evidence from the first WHO guidelines for risk reduction of cognitive decline and dementia indicated that "one size does not fit all," and multidomain approaches adaptable to different populations and individuals are likely to be the most effective. Harmonization in trial design, the use of appropriate outcome measures, and sustainability in large at-risk populations in the context of other chronic disorders also emerged as key elements., Competing Interests: KA is an advisor to Staying Sharp. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Stephen, Barbera, Peters, Ee, Zheng, Lehtisalo, Kulmala, Håkansson, Chowdhary, Dua, Solomon, Anstey and Kivipelto.)

Endoscopic ultrasound-ablation with HybridTherm-Probe (EUS-HTP) significantly reduces tumour volume (TV) in locally-advanced pancreatic ductal adenocarcinoma (LA-PDAC). We aimed at investigating the clinical efficacy of EUS-HTP plus chemotherapy versus chemotherapy (HTP-CT and CT arms) in LA- and borderline-resectable (BR) PDAC, with 6-months progression-free survival (6-PFS) rate as primary endpoint. In a phase-II randomized-controlled-trial, 33 LA/BR-PDAC patients per-arm were planned to verify 20% improved 6-PFS rate. Radiological response (Choi criteria), TV and serum CA19.9 were assessed up to 6-months. Seventeen and 20 LA/BR-PDAC patients were randomized to HTP-CT or CT. Baseline and CT-related features were balanced. At 6-months, 6-PFS rate was 41.2% and 30% in HTP-CT and CT arms ( p = 0.48), respectively. A decrease ≥50% of serum CA19.9 was achieved in 75% and 64.3% of HTP-CT and CT patients ( p = 0.53), respectively. TV reduced up to 6-months in 64.3% and 47.1% of HTP-CT and CT patients ( p = 0.35), respectively. Resection rate, PFS-time and overall survival (OS-time) were similar. HTP-CT achieves a non-significant 11.2%, 10.7% and 17.2% improved 6-PFS, CA19.9 decrease ≥50% and TV reduction rates over CT, without any impact on resection rate, PFS-time and OS-time. As the study was underpowered, these results suggest further investigation of EUS-local ablation in selected patients with localized disease after induction CT.

Purpose: To assess the ability of radiomic features (RF) extracted from contrast-enhanced CT images (ceCT) and non-contrast-enhanced (non-ceCT) in discriminating histopathologic characteristics of pancreatic neuroendocrine tumors (panNET)., Methods: panNET contours were delineated on pre-surgical ceCT and non-ceCT. First- second- and higher-order RF (adjusted to eliminate redundancy) were extracted and correlated with histological panNET grade (G1 vs G2/G3), metastasis, lymph node invasion, microscopic vascular infiltration. Mann-Whitney with Bonferroni corrected p values assessed differences. Discriminative power of significant RF was calculated for each of the end-points. The performance of conventional-imaged-based-parameters was also compared to RF., Results: Thirty-nine patients were included (mean age 55-years-old; 24 male). Mean diameters of the lesions were 24 × 27 mm. Sixty-nine RF were considered. Sphericity could discriminate high grade tumors (AUC = 0.79, p = 0.002). Tumor volume (AUC = 0.79, p = 0.003) and several non-ceCT and ceCT RF were able to identify microscopic vascular infiltration: voxel-alignment, neighborhood intensity-difference and intensity-size-zone families (AUC ≥ 0.75, p < 0.001); voxel-alignment, intensity-size-zone and co-occurrence families (AUC ≥ 0.78, p ≤ 0.002), respectively). Non-ceCT neighborhood-intensity-difference (AUC = 0.75, p = 0.009) and ceCT intensity-size-zone (AUC = 0.73, p = 0.014) identified lymph nodal invasion; several non-ceCT and ceCT voxel-alignment family features were discriminative for metastasis (p < 0.01, AUC = 0.80-0.85). Conventional CT 'necrosis' could discriminate for microscopic vascular invasion (AUC = 0.76, p = 0.004) and 'arterial vascular invasion' for microscopic metastasis (AUC = 0.86, p = 0.001). No conventional-imaged-based-parameter was significantly associated with grade and lymph node invasion., Conclusions: Radiomic features can discriminate histopathology of panNET, suggesting a role of radiomics as a non-invasive tool for tumor characterization., Trial Registration Number: NCT03967951, 30/05/2019.

Background: Evidence from animal studies suggests that greater reductions in poststroke motor impairment can be attained with significantly higher doses and intensities of therapy focused on movement quality. These studies also indicate a dose-timing interaction, with more pronounced effects if high-intensity therapy is delivered in the acute/subacute, rather than chronic, poststroke period., Objective: To compare 2 approaches of delivering high-intensity, high-dose upper-limb therapy in patients with subacute stroke: a novel exploratory neuroanimation therapy (NAT) and modified conventional occupational therapy (COT)., Methods: A total of 24 patients were randomized to NAT or COT and underwent 30 sessions of 60 minutes time-on-task in addition to standard care. The primary outcome was the Fugl-Meyer Upper Extremity motor score (FM-UE). Secondary outcomes included Action Research Arm Test (ARAT), grip strength, Stroke Impact Scale hand domain, and upper-limb kinematics. Outcomes were assessed at baseline, and days 3, 90, and 180 posttraining. Both groups were compared to a matched historical cohort (HC), which received only 30 minutes of upper-limb therapy per day., Results: There were no significant between-group differences in FM-UE change or any of the secondary outcomes at any timepoint. Both high-dose groups showed greater recovery on the ARAT (7.3 ± 2.9 points; P = .011) but not the FM-UE (1.4 ± 2.6 points; P = .564) when compared with the HC., Conclusions: Neuroanimation may offer a new, enjoyable, efficient, and scalable way to deliver high-dose and intensive upper-limb therapy.

Sustainable agricultural, food-related strategies and geographic traceability require understanding of the plant physiological response to stress potentially generated by contaminated soils. Here, we have investigated the effect of contaminated substrate on growth of Vitis vinifera L. plants analysing the distribution of full Rare Earth Elements (REE) spectra in different parts of the plant. Experiments were carried out using pristine plants growing in a handmade substrate (blank experiment) and in REE artificially-enriched soil (spiked experiment). Our results show that both plant mass and REE amount in leaves are not influenced by the substrate enrichment while roots are by one-order of magnitude enriched for three-orders of magnitude enhancement of the soil substrate. This clearly indicates that soil contamination does not significantly influence the REE amount in the aerial parts. However, the spectra of REE normalized changes when the soil is enriched. We found that Light-REE (from La to Gd) are by more than one order of magnitude enriched compared to Heavy-REE (from Tb to Lu plus Y) in spiked experiment showing the specific response of Vitis vinifera L. to the stress generated by soil contamination. We propose that REE distribution spectra is a marker of Vitis vinifera L. substrate of growth and providing a new tool for tracing the geographical origin of agri-food products., Competing Interests: Declaration of competing interest All authors have read and understood the requirements of the Journal. We declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Fresh ovine "primosale" cheese was processed with the addition of grape pomace powder (GPP). Cheese making was performed using pasteurized ewes' milk and four selected Lactococcus lactis strains (Mise36, Mise94, Mise169 and Mise190) inoculated individually. For each strain the control cheese (CCP) was not added with GPP, while the experimental cheese (ECP) was enriched with 1% ( w / w ) GPP. GPP did not influence the starter development that reached levels of 10 9 CFU/g in all final cheeses. The comparison of the bacterial isolates by randomly amplified polymorphic DNA (RAPD)-PCR showed the dominance of the added strains over indigenous milk bacteria resistant to pasteurization. GPP addition reduced fat content and determined an increase of protein and of secondary lipid oxidation. Sensory tests indicated that cheeses CCP94 and ECP94, produced with the strain Mise94, reached the best appreciation scores. Following in vitro simulated human digestion, bioaccessible fraction of ECP94 showed antioxidant capacity, evaluated as radical scavenging activity and inhibition of membrane lipid oxidation, significantly higher than that from CCP94, with promising increase in functional properties. Thus, the main hypothesis was accepted since the functional aspects of the final cheeses improved, confirming that GPP is relevant for sustainable nutrition by using winemaking by-products.

An innovative ovine cheese enriched with red grape pomace powder (GPP) was produced to improve the functional properties of Vastedda cheese typology. Vastedda cheese making was performed adding GPP and four selected Lactococcus lactis strains (Mise36, Mise94, Mise169 and Mise190). For each strain, 40 L of pasteurized ewe's milk was divided into two aliquots representing control and experimental trials. Control cheese (CC) production did not contain GPP, while the experimental cheese (EC) production was enriched with 1% ( w / w ) GPP. GPP did not slow down starter development and acid generation. Plate counts and randomly amplified polymorphic DNA (RAPD)-PCR analysis confirmed the dominance of the starters in all trials. The evolution of the physicochemical parameters showed that EC productions were characterized by lower fat content, higher protein content, and higher values of secondary lipid oxidation. Sensory evaluation indicated that the cheeses produced with the strain Mise94 were those more appreciated by the judges. Thus, the last cheeses were investigated for some functional aspects: GPP enrichment significantly increased antioxidant activity and lipoperoxyl radical scavenger capacity, confirming that grape polyphenol inclusion in cheese represents an optimal strategy for the valorization of ovine cheeses as well as winemaking industry by-products.

Background and study aims  Endoscopic ultrasound (EUS)-guided ablation of pancreatic ductal adenocarcinoma (PDAC) with HybridTherm-Probe (EUS-HTP) is feasible and safe, but the radiological response and ideal tool to measure it have not been investigated yet. The aims of this study were to: 1) assess the radiological response to EUS-HTP evaluating the vital tumor volume reduction rate, Response Evaluation Criteria in Solid Tumors (RECIST1.1) and Choi criteria; 2) determine the prognostic predictive yield of these criteria. Patients and methods  A retrospective analysis was performed of patients with locally advanced PDAC after primary treatment or unfit for chemotherapy prospectively treated by EUS-HTP. Computed tomography scan was performed 1 month after EUS-HTP to evaluate: 1) vital tumor volume reduction rate (VTVRR) by measuring necrosis and tumor volumes through a computer-aided detection system; and 2) RECIST1.1 and Choi criteria. Results  EUS-HTP was feasible in 22 of 31 patients (71 %), with no severe adverse events. Median post-HTP survival was 7 months (1 - 35). Compared to pre-HTP tumor volume, a significant 1-month VTVRR (mean 21.4 %) was observed after EUS-HTP ( P  = 0.005). We identified through ROC analysis a VTVRR > 11.46 % as the best cut-off to determine post-HTP 6-month survival outcome (AUC = 0.733; sensitivity = 70.0 %, specificity = 83.3 %). This cut-off was significantly associated with longer overall survival (HR = 0.372; P  = 0.039). According to RECIST1.1 and Choi criteria, good responders to EUS-HTP were 60 % and 46.7 %, respectively. Good responders according to Choi, but not to RECIST1.1, had longer survival (HR = 0.407; P  = 0.04). Conclusions  EUS-HTP induces a significant 1-month VTVRR. This effect is assessed accurately by evaluation of necrosis and tumor volumes. Use of VTVRR and Choi criteria, but not RECIST 1.1 criteria, might identify patients who could benefit clinically from EUS-HTP., Competing Interests: Competing interests Prof. M. Enderle and Dr. W. Linzenbold are employees of the research department of Erbe Elektromedizin GmbH, Tubingen, Germany., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objectives: Prevention of cardiovascular disease (CVD) and dementia is a key health priority among older adults. Understanding individuals' attitudes to, the prevention of these conditions, particularly when delivered through novel eHealth tools, could help in designing effective prevention programmes. The aim of the study was to explore the attitudes of older adults at increased risk of CVD and dementia regarding engagement in eHealth self-management prevention programmes, and to describe the facilitators and barriers., Design: A qualitative research approach was used. Data were collected through eight focus groups in Finland, France and the Netherlands. Data were analysed following the principles of grounded theory., Setting and Participants: Forty-four community-dwellers aged 65+ at risk of CVD were recruited from a previous trial cohort in Finland, and through general practices in France and the Netherlands., Results: The study identified three categories: access to reliable information, trust in the healthcare providers and burden and stigma of dementia. A core category was also identified: the interactive process of the three categories influencing engagement in self-management prevention programme. The categories were interconnected through an interactive process and influenced by the local healthcare culture and context which shaped them differently, becoming either facilitators or barriers to engage in eHealth self-management prevention programmes., Conclusions: The study emphasises the importance of considering the interactions between the identified categories in this study, grounded in the local healthcare culture and context in further developments of eHealth self-management interventions that aim to prevent CVD and dementia., Trial Registration Number: ISRCTN48151589., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: The oldest old is the fastest growing age group worldwide and the most prone to severe disability, especially in relation to loss of cognitive function. Improving our understanding of the predictors of cognitive, physical and psychosocial wellbeing among the oldest old can result in substantial benefits for the individuals and for the society as a whole. The Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study investigated risk factors and determinants of cognitive impairment in a population-based longitudinal cohort, which was first examined between 1972 and 1992, when individuals were in their midlife, and re-assessed in 1998 and 2005-2009. Most of the study participants are currently aged 85 years or older. We aim to re-examine the cohort's survivors and gain further insights on the mechanisms underlying both cognitive and overall healthy ageing at old age., Methods: CAIDE85+ is the third follow-up of the CAIDE study participants. All individuals still alive and living in the Kuopio and Joensuu areas of Eastern Finland, from the original CAIDE cohort (two random samples, N = 2000 + ~ 900), will be invited to a re-examination. The assessment includes self-reported data related to basic demographics and lifestyle, as well as psychosocial and physical health status. Cognitive and physical evaluations are also conducted. Blood biomarkers relevant for dementia and ageing are assessed. Primary outcomes are the measurements related to cognition and daily life functioning (CERAD, Trail Making Test-A, Letter-Digit Substitution Test, Clinical Dementia Rating and Activities of Daily Living). Secondary endpoints of the study are outcomes related to physical health status, psychosocial wellbeing, as well as age-related health indicators., Discussion: Through a follow-up of more than 40 years, CAIDE85+ will provide invaluable information on the risk and protective factors that contribute to cognitive and physical health, as well as ageing and longevity., Study Registration: The present study protocol has been registered at https://clinicaltrials.gov/ (registration nr NCT03938727 , date 03.05.2019).

Phenols or phenolics are a class of compounds that have one or more hydroxyl groups attached to a 6-carbon aromatic ring, they occur as plant secondary metabolites, having in common the antioxidant activity. Their average daily intake varies widely around the world. Many researchers consider coffee, tea, wine, cocoa products, fruits and vegetables as the main sources of polyphenols in different diets. However, spices and culinary herbs have been referred to as the foods richest in polyphenols. Despite spices and culinary herbs are used in small amounts as seasonings, their contribution to the dietary supply of phytonutrients should not be disregarded. A diet rich in a variety of polyphenols (and other phytonutrients) has potential health benefits, namely in the prevention of chronic diseases and cancer. In addition, flavor and color are the most important factors for the selection of food by consumers. A multitude of endogenous food compounds, including phenolics, are involved in food flavor. The presence of phenolic compounds in the food matrix has been mainly associated with the perception of bitter taste and tactile sensation of astringency. However, these compounds can also impact the color and aroma notes of fruits and vegetables. Thus, understanding the sensory impact of these substances and relationships with consumers' approaches towards phenolic-rich fruits and vegetables may help find strategies to increase the consumption of such foods. A well-known example of a tasty, healthy and sustainable dietary model is the Mediterranean Diet. In this study, we summarize the dietary intake of some polyphenols from different dietary patterns around the world and the contribution of natural phenolic compounds to the flavor of food and beverages, in particularly those associated to the Mediterranean Diet., (© AOAC INTERNATIONAL 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The problem of waste and byproducts generated from agro-industrial activities worldwide is an increasing concern in terms of environmental sustainability. In this ambit, the quantity of food wastes-produced in all steps of the whole food chain-is enormous, and it may be forecasted that food waste could amount to more than 120 billion tonnes by 2020. The reuse of food waste and wastewater as source of polyphenolic compounds could be an interesting discussion in this ambit. In fact, polyphenols obtained in this way might be used for food and non-food purposes by means of new, improved, and safe extraction methods. In light of the opportunity represented by the treatment of agro-industrial waste, different systems concerning the winemaking and olive oil production industries have also been discussed as describing approaches applicable to other sectors. More research is needed before considering recovery of phenolic compounds from wastewater as an economically convenient choice for the food sector., (© AOAC INTERNATIONAL 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In the present case, we report the first experience of a patient with high-grade glioma who underwent dual F-FAZA PET/CT imaging for intratumoral hypoxia assessment, before treatment, and for therapy monitoring in the suspicious of recurrence, as part of a clinical research protocol. In addition, despite the diagnosis of glioblastoma, the patient at 3 years from diagnosis was alive and underwent C-methionine simultaneous PET/MRI for disease monitoring after treatment, showing stability of disease. The multitracer capability of PET in assessing different and complementary metabolic features along with the use of a last-generation scanner as PET/MRI in brain oncology are here enlighten.

Pistachio powder was added to flour or semolina to evaluate its contribution to increase the amount of lysine in bread. Bread production was carried out by sourdough technology using a selected 3-species (Lactobacillus sanfranciscensis/Leuconostoc citreum/Weissella cibaria) lactic acid bacterial (LAB) starter culture. All sourdoughs were subjected to a long-time fermentation (21 h) and showed levels of LAB around 10 9  CFU/g, indicating the suitability of pistachio powder for lactic fermentation. Yeasts were also detected, in particular in semolina trials. MiSeq Illumina technology was applied to investigate the bacterial composition of sourdoughs evidencing a different distribution of LAB species among the trials with Lactobacillus as major LAB group in almost all sourdoughs. Physicochemical parameters were comparable among the trials. After baking, pistachio powder was found not to influence the height of the breads, but pistachio breads were more firm than control breads. Color of the breads, void fraction and cell density, were influenced by pistachio powder. The amount of lysine increased consistently thanks to pistachio supplementation which also determined a higher presence of o-xylene, p-cymene and limonene and the appearance of α-pinene and 1-octen-3-ol in breads. Sensory tests showed the best appreciation scores for the breads produced with flour and pistachio powder., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: A better insight into older adults' understanding of and attitude towards cognitive disorders and their prevention, as well as expectations and reasons for participation in prevention trials, would help design, conduct, and implement effective preventive interventions. This qualitative study aimed at exploring the knowledge and perceptions of cognitive disorders and their prevention among participants in a prevention trial., Methods: Semi-structured interviews were conducted among the participants of a multinational randomised controlled trial testing the efficacy of a lifestyle-based eHealth intervention in preventing cardiovascular disease or cognitive decline in community dwellers aged 65+. Participants were probed on their reasons for participation in the trial and their views on general health, cardiovascular disease, ageing, and prevention. The subset of data focusing on cognitive disorders (15 interviewees; all in Finland) was considered for this study. Data were analysed using content analysis., Results: Participants' knowledge of the cause and risk factors of cognitive disorders and prevention was limited and superficial, and a need for up-to-date, reliable, and practical information and advice was expressed. Cognitive disorders evoked fear and concern, and feelings of hopelessness and misery were frequently expressed, indicating a stigma. Strong heredity of cognitive disorders was a commonly held belief, and opinions on the possibility of prevention were doubtful, particularly in relation to primary prevention. Family history and/or indirect experiences of cognitive disorders was a recurrent theme and it showed to be linked to both the knowledge of and feelings associated with cognitive disorders, as well as attitude towards prevention. Indirect experiences were linked to increased awareness and knowledge, but also uncertainty about risk factors and possibility of prevention. Distinct fear and concerns, particularly over one's own cognition/risk, and high motivation towards engaging in prevention and participating in a prevention trial were also identified in connection to this theme., Conclusions: Family history and/or indirect experiences of cognitive disorders were linked to sensitivity and receptiveness to brain health and prevention potential. Our findings may be helpful in addressing older adults' expectations in future prevention trials to improve recruitment, maximise adherence, and facilitate the successful implementation of interventions.

Objective: As no causal treatment for dementia is available yet, the focus of dementia research is slowly shifting towards prevention strategies. Therefore, this study aimed to examine the predictive accuracy of the "LIfestyle for BRAin Health" (LIBRA) score, a weighted compound score of 12 modifiable risk and protective factors, for dementia and mild cognitive impairment (MCI) in midlife and late-life, and in individuals with high or low genetic risk based on presence of the apolipoprotein (APOE) ε4 allele., Methods: The LIBRA score was calculated for participants from the Finnish Cardiovascular Risk Factors, Aging and Dementia (CAIDE) population-based study examined in midlife (n = 1024) and twice in late-life (n = 604) up to 30 years later. Diagnoses of MCI and dementia were made according to established criteria. Cox proportional hazards models were used to assess the association between LIBRA and risk of dementia and MCI in models adjusted for sex and education (age as timescale)., Results: Higher midlife LIBRA scores were related to higher risk of dementia (hazard ratio [HR] = 1.27; 95% confidence interval [CI], 1.13-1.43) and MCI (unadjusted model: HR = 1.12; 95% CI, 1.03-1.22) up to 30 years later. Higher late-life LIBRA scores were related to higher risk of MCI (HR = 1.11; 95% CI, 1.00-1.25), but not dementia (HR = 1.02; 95% CI, 0.84-1.24). Higher late-life LIBRA scores were related to higher dementia risk among apolipoprotein E (APOE) ε4 non-carriers., Conclusions: Findings emphasize the importance of modifiable risk and protective factors for dementia prevention., (© 2019 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Background: Although web-based interventions have been promoted for cardiovascular risk management over the past decade, there is limited evidence for effectiveness of these interventions in people older than 65 years. The healthy ageing through internet counselling in the elderly (HATICE) trial aimed to determine whether a coach-supported internet intervention for self-management can reduce cardiovascular risk in community-dwelling older people., Methods: This prospective open-label, blinded endpoint clinical trial among people age 65 years or over at increased risk of cardiovascular disease randomly assigned participants in the Netherlands, Finland, and France to an interactive internet intervention stimulating coach-supported self-management or a control platform. Primary outcome was the difference from baseline to 18 months on a standardised composite score (Z score) of systolic blood pressure, LDL cholesterol, and body-mass index (BMI). Secondary outcomes included individual risk factors and cardiovascular endpoints. This trial is registered with the ISRCTN registry, 48151589, and is closed to accrual., Findings: Among 2724 participants, complete primary outcome data were available for 2398 (88%). After 18 months, the primary outcome improved in the intervention group versus the control group (0·09 vs 0·04, respectively; mean difference -0·05, 95% CI -0·08 to -0·01; p=0·008). For individual components of the primary outcome, mean differences (intervention vs control) were systolic blood pressure -1·79 mm Hg versus -0·67 mm Hg (-1·12, -2·51 to 0·27); BMI -0·23 kg/m 2 versus -0·08 kg/m 2 (-0·15, -0·28 to -0·01); and LDL -0·12 mmol/L versus -0·07 mmol/L (-0·05, -0·11 to 0·01). Cardiovascular disease occurred in 30 (2·2%) of 1382 patients in the intervention versus 32 (2·4%) of 1333 patients in the control group (hazard ratio 0·86, 95% CI 0·52 to 1·43)., Interpretation: Coach-supported self-management of cardiovascular risk factors using an interactive internet intervention is feasible in an older population, and leads to a modest improvement of cardiovascular risk profile. When implemented on a large scale this could potentially reduce the burden of cardiovascular disease., Funding: European Commission Seventh Framework Programme., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To explore older adults' reasons for participating in a multinational eHealth prevention trial, and compare motivations between countries., Design: Cross-sectional mixed methods research using quantitative and qualitative approaches (the ACCEPT-HATICE study)., Setting and Participants: Substudy conducted during the recruitment phase of an 18-month RCT testing the efficacy of an eHealth intervention for self-management of risk factors for cardiovascular disease (CVD) and cognitive decline in older adults in Finland, France, and the Netherlands. Participants were 343 dementia-free community dwellers aged 65+ with basic computer literacy and either ≥2 cardiovascular risk factors or a history of CVD/diabetes., Measures: Online questionnaire (quantitative data) and semistructured interviews (qualitative data)., Results: Contributing to scientific progress, wanting to improve one's lifestyle, and benefiting from additional medical monitoring were the predominant reasons for participating. Altruistic reasons were particularly relevant among the French, whereas Finnish and Dutch participants mainly emphasized the benefits of lifestyle changes and regular medical checkups. During interviews, preventing functional dependency emerged as a key underlying motivation. Although some trial design features influenced the decision to participate, the use of an eHealth intervention was not an important motivator in this population., Conclusions/implications: Altruism and personal benefits motivated older adults to participate in the trial; emphasizing such aspects could facilitate recruitment in future RCTs. Additional medical monitoring may be particularly appealing when access to public health care is considered limited. Furthermore, maintaining autonomy and preventing functional dependency emerged as a key concern in this population of young older adults., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Global ageing is linked to an increased burden of cardiovascular disease and dementia, which calls for better prevention strategies. Self-management and eHealth applications are regarded as promising strategies to support prevention. The aim of this study was to explore nurses' best practices concerning behaviour change guidance for cardiovascular (CV) prevention in order to learn how to optimally integrate them into a coach-supported internet platform for CV self-management., Design: Qualitative focus group study in Finland and the Netherlands. Discussions were audiotaped and transcribed. Data were thematically analysed following principles of grounded theory., Setting: Dutch and Finnish primary care settings., Participants: Six Finnish and seven Dutch primary care nurses with experience in CV prevention., Results: Similar best practices were found in both countries and comprised of (1) establishing a relationship of trust, (2) managing awareness and expectations and (3) appropriate timing and monitoring of the process of behaviour change. However, the Finnish and Dutch nurses used different approaches for accomplishment of these practices, which was reflected in their recommendations for online support. Both groups emphasised that online support should be combined with human support and integrated into regular care. Finnish nurses had more confidence in patient self-management and remote communication than Dutch nurses, who emphasised the importance of face-to-face contact and preferred to keep control of medical aspects of prevention., Conclusions: Differences in Dutch and Finnish's nurses' practices for supporting CV prevention appear to reflect their local healthcare practices, which should be taken into account when designing internet platforms for health self-management. Including cognitive health as a goal of CV prevention might stimulate motivation for health behaviour change., Trial Registration Number: ISRCTN48151589; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Bituminaria bituminosa (C.H. Stirt.) is a drought tolerant legume that grows spontaneously in subtropical areas: Canary Islands (Spain) and in North African and Mediterranean regions, traditionally used as forage for ruminants. The aim of this research was to investigate the potential of B. bituminosa as a high protein resource for poultry feed by means of feed intake, growth, feed conversion rate (FCR), protein efficiency ratio (PER), and the influence of B. bituminosa feed form (fresh green and dried) on the preference by chicks. B. bituminosa showed higher crude protein content (CP), neutral detergent fiber (NDF), and gross energy than commercial feed. Average daily feed intake (ADFI) for the commercial feed group (control group) was higher than ADFI of the B. bituminosa group (experimental group). However, both groups had no significant differences in total crude protein intake, total NDF intake, average daily gain (ADG), FCR, and PER. The poultry's preference for fresh green B. bituminosa was higher than for dry B. bituminosa. Our results suggest that B. bituminosa (tedera) could be an alternative feedstuff in tropical countries or where protein sources are scarce and costly.

Purpose: The aim of this study was to quantify the impact of CT delineation uncertainty of pancreatic neuroendocrine neoplasms (panNEN) on Radiomic features (RF)., Methods: Thirty-one previously operated patients were considered. Three expert radiologists contoured panNEN lesions on pre-surgical high-resolution contrast-enhanced CT images and contours were transferred onto pre-contrast CT. Volume agreement was quantified by the DICE index. After images resampling and re-binning, 69 RF were extracted and the impact of inter-observer variability was assessed by Intra-Class Correlation (ICC): ICC > 0.80 was considered as a threshold for "very high" inter-observer agreement., Results: The median volume was 1.3 cc (range: 0.2-110 cc); a satisfactory inter-observer volume agreement was found (mean DICE = 0.78). Only 4 RF showed ICC < 0.80 (0.48-0.73), including asphericity and three RFs (of five) of the neighborhood intensity difference matrix (NID)., Conclusions: The impact of inter-observer variability in delineating panNEN on RF was minimum, with the exception of the NID family and asphericity, showing a moderate agreement. These results support the feasibility of studies aiming to assess CT radiomic biomarkers for panNEN., (Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

The objective of this study was to evaluate the effects of replacing rye-grass (Lolium spp.) hay with banana (Musa acuminata L.) by-products on feed intake, average daily gain (ADG), and feed conversion rate (FCR) in Pelibuey (hair sheep breed) lambs. The lambs (n = 22; initial BW = 14.8 ± 2.5 kg) were individually housed and fed on two different types of diet for 58 days: the first group (experimental diet) received as forage a mixture of fresh banana by-products composed of leaves and pseudostem. The second group received commercial rye-grass hay (conventional diet) as a fiber source. Both groups received a supplementary commercial concentrate food. The total daily forage intake and FCR were lower (P < 0.001) in animals fed on the conventional diet (rye-grass hay) than animals fed on the experimental diet (banana by-products). However, there were no significant differences in total dry matter intake, total digestible energy intake, total body weight gain, and ADG between the two groups. The results obtained in this study suggest that banana by-products could be used as alternative forage for Pelibuey lambs raised in subtropical conditions.

Objectives: To study older peoples' experiences with an interactive internet platform for cardiovascular self-management, to assess which factors influence initial and sustained engagement. To assess their views on future use within primary care., Design: Qualitative semistructured interview study, with thematic analysis., Setting: Primary care in the Netherlands., Participants: People ≥65 years with an increased risk of cardiovascular disease who used the 'Healthy Ageing Through Internet Counselling in the Elderly' internet platform with remote support of a coach. Participants were selected using a purposive sampling method based on gender, age, level of education, cardiovascular history, diabetes, duration of participation and login frequency., Results: We performed 17 interviews with 20 participants, including three couples. In the initial phase, platform engagement was influenced by perceived computer literacy of the participants, user-friendliness, acceptability and appropriateness of the intervention and the initial interaction with the coach. Sustained platform use was mainly facilitated by a relationship of trust with the coach. Other facilitating factors were regular automatic and personal reminders, clear expectations of the platform, incorporation into daily routine, social support and a loyal and persistent attitude. Perceived lack of change in content of the platform could work both stimulating and discouraging. Participants supported the idea of embedding the platform into the primary care setting., Conclusions: Human support is crucial to initial and sustained engagement of older people in using an interactive internet platform for cardiovascular self-management. Regular reminders further facilitate sustained use, and increased tailoring to personal preference is recommended. Embedding the platform in primary healthcare may enhance future adoption., Trial Registration Number: ISRCTN48151589; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Many dementia and cardiovascular disease (CVD) cases in older adults are attributable to modifiable vascular and lifestyle-related risk factors, providing opportunities for prevention. In the Healthy Aging Through Internet Counselling in the Elderly (HATICE) randomized controlled trial, an internet-based multidomain intervention is being tested to improve the cardiovascular risk (CVR) profile of older adults., Objective: To design a multidomain intervention to improve CVR, based on the guidelines for CVR management, and administered through a coach-supported, interactive, platform to over 2500 community-dwellers aged 65+ in three European countries., Methods: A comparative analysis of national and European guidelines for primary and secondary CVD prevention was performed. Results were used to define the content of the intervention., Results: The intervention design focused on promoting awareness and self-management of hypertension, dyslipidemia, diabetes mellitus, and overweight, and supporting smoking cessation, physical activity, and healthy diet. Overall, available guidelines lacked specific recommendations for CVR management in older adults. The comparative analysis of the guidelines showed general consistency for lifestyle-related recommendations. Key differences, identified mostly in methods used to assess the overall CVR, did not hamper the intervention design. Minor country-specific adaptations were implemented to maximize the intervention feasibility in each country., Conclusion: Despite differences in CVR management within the countries considered, it was possible to design and implement the HATICE multidomain intervention. The study can help define preventative strategies for dementia and CVD that are applicable internationally.

The essential oils (EOs) of green seeds from Daucus carota subsp. maximus growing wild in Pantelleria Island (Sicily, Italy) were characterized. EOs were extracted by steam distillation, examined for their inhibitory properties against food-borne Gram-positive and Gram-negative bacteria and analyzed for the chemical composition by gas chromatography (GC) and mass spectrometry (MS). Undiluted EOs showed a large inhibition spectrum against Gram-positive strains and also vs. Acinetobacter spp. and Stenotrophomonas maltophilia. The minimum inhibition concentration (MIC) was in the range 1.25 - 2.50 μl/ml for the most sensitive strains. The chemical analysis indicated that D. carota subsp. maximus EOs included 34 compounds (five monoterpene hydrocarbons, six oxygenated monoterpenes, 14 sesquiterpene hydrocarbons, four oxygenated sesquiterpenes, camphorene and four other compounds), accounting for 95.48% of the total oil, and that the major chemicals were carotol, β-bisabolene, and isoelemicin., (© 2017 Wiley-VHCA AG, Zurich, Switzerland.)

Background: A myriad of Web-based applications on self-management have been developed, but few focus on older people. In the face of global aging, older people form an important target population for cardiovascular prevention. This article describes the full development of an interactive Internet platform for older people, which was designed for the Healthy Ageing Through Internet Counselling in the Elderly (HATICE) study. We provide recommendations to design senior-friendly Web-based applications for a new approach to multicomponent cardiovascular prevention., Methods: The development of the platform followed five phases: (1) conceptual framework; (2) platform concept and functional design; (3) platform building (software and content); (4) testing and pilot study; and (5) final product., Results: We performed a meta-analysis, reviewed guidelines for cardiovascular diseases, and consulted end users, experts, and software developers to create the platform concept and content. The software was built in iterative cycles. In the pilot study, 41 people aged ≥65 years used the platform for 8 weeks. Participants used the interactive features of the platform and appreciated the coach support. During all phases adjustments were made to incorporate all improvements from the previous phases. The final platform is a personal, secured, and interactive platform supported by a coach., Discussion: When carefully designed, an interactive Internet platform is acceptable and feasible for use by older people with basic computer skills. To improve acceptability by older people, we recommend involving the end users in the process of development, to personalize the platform and to combine the application with human support. The interactive HATICE platform will be tested for efficacy in a multinational randomized controlled trial (ISRCTN48151589).

Ocular motor palsy is a rare but alarming complication of subarachnoid puncture. In order to better understand this condition, a literature search was performed in English of PubMed articles for cranial nerves III, IV, and VI palsies after spinal puncture. Sixty-five articles (dated 1930-2015) were identified, and 114 cases were obtained for analysis. Subarachnoid anesthesia was the most frequent cause (45.6%), with a higher incidence for females than males. The age of patients was 40.24 ± 13.35 years (age range, 6-71 years). The sixth cranial nerve was the most commonly involved (92.1%), with higher frequency in the right eye. Palsy onset started 7.30 ± 4.09 days after puncture. Duration in reversible cases was 80.10 ± 80.67 days. Paresia was permanent in 13 patients, but only 2 patients required extraocular muscle surgery. Treatments included the horizontal position along with analgesics, fluid therapy, and corticosteroids. The usefulness of blood patch remains controversial. It is important for anesthesiologists and other physicians to recognize the cardinal features of this process to ensure early diagnosis, avoid unnecessary tests, and guide appropriate treatment.

Uric acid calculi can also be treated without surgery, with simple medical lytic therapy. After appropriate dietary adjustments and add of mineral water, the needed amount of alkali supplementation can increase pH values of the urine in order to dissolve the stones. Treatment should be prolonged to prevent stone recurrence. A case of bilateral renal uric acid stones that were successfully treated by alakalizing treatment was presented.

About 10% of the people is the subject of an episode of kidney stones during their lifetime, about 70% of these people undergoes relapses. About 80% of the urinary stones contains calcium, of wich 80% is formed of calcium oxalate, in pure form or associated with calcium phosphate. Therefore we can saythat in most cases (about 65%) the urinary stones are composedof calcium oxalate. Use of supplements of potassium citrate and magnesium citrate can help in the prevention of kidney stones of calcium oxalate, but mostly they can be used in the days before a shockwaves lithotripsy treatment to make the stones more fragile to the effect of the shock waves. A case of successful treatment with magnesium potassium citrate of a SWL resistant ureteral stone is presented.

Introduction: The detection rate for significant prostate cancer of extended vs saturation vs mMRI/TRUS fusion biopsy was prospectively evaluated in men enrolled in active surveillance (AS) protocol. Mterials and methods: From May 2013 to September 2016 75 men aged 66 years (median) with very low risk PCa were enrolled in an AS protocol and elegible criteria were: life expectancy greater than 10 years, cT1C, PSA below 10 ng/ml, PSA density &lt; 0.20, 2 &lt; unilateral positive biopsy cores, Gleason score (GS) equal to 6, greatest percentage of cancer (GPC) in a core &lt; 50%. All patients underwent 3.0 Tesla pelvic mpMRI before confirmatory transperineal extended (20 cores) or saturation biopsy (SPBx; 30 cores) combined with mpMRI/TRUS fusion targeted biopsy (4 cores) of suspicious lesions (PI-RADS 3-5)., Results: 21/75 (28%) patients were reclassified by SPBx based on upgraded GS ≥ 7; mpMRI lesions PI-RADS 4-5 vs PI-RADS 3-5 diagnosed 9/21 (42.8%) vs 16/21 (76.2%) significant PCa with 2 false positives (6.5%). The detection rate for significant PCa was equal to 76.2% (mpMRI/TRUS fusion biopsy) vs 81% (extended) vs 100% (SPBx) (p = 0.001); mpMRI/TRUS targeted biopsy and extended biopsy missed 5/21 (23.8%) and 4/21 (19%) significant PCa which were found by SPBx (p = 0.001) being characterised by the presence of a single positive core of GS ≥ 7 with GPC &lt; 10%., Conclusions: Although mpMRI improve the diagnosis of clinically significant PCa, SPBx is provided of the best detection rate for PCa in men enrolled in AS protocols who underwent confirmatory biopsy.

Introduction: Cardiovascular disease and dementia share a number of risk factors including hypertension, hypercholesterolaemia, smoking, obesity, diabetes and physical inactivity. The rise of eHealth has led to increasing opportunities for large-scale delivery of prevention programmes encouraging self-management. The aim of this study is to investigate whether a multidomain intervention to optimise self-management of cardiovascular risk factors in older individuals, delivered through an coach-supported interactive internet platform, can improve the cardiovascular risk profile and reduce the risk of cardiovascular disease and cognitive decline., Methods and Analysis: HATICE is a multinational, multicentre, prospective, randomised, open-label blinded end point (PROBE) trial with 18 months intervention. Recruitment of 2600 older people (≥65 years) at increased risk of cardiovascular disease will take place in the Netherlands, Finland and France. Participants randomised to the intervention condition will have access to an interactive internet platform, stimulating self-management of vascular risk factors, with remote support by a coach. Participants in the control group will have access to a static internet platform with basic health information.The primary outcome is a composite score based on the average z-score of the difference between baseline and 18 months follow-up values of systolic blood pressure, low-density-lipoprotein and body mass index. Main secondary outcomes include the effect on the individual components of the primary outcome, the effect on lifestyle-related risk factors, incident cardiovascular disease, mortality, cognitive functioning, mood and cost-effectiveness., Ethics and Dissemination: The study was approved by the medical ethics committee of the Academic Medical Center in Amsterdam, the Comité de Protection des Personnes Sud Ouest et Outre Mer in France and the Northern Savo Hospital District Research Ethics Committee in Finland.We expect that data from this study will result in a manuscript published in a peer-reviewed clinical open access journal., Trial Registration Number: ISRCTN48151589., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

In this work, an ad hoc method to identify and quantify polyphenols from caper berries was developed on high-performance liquid chromatography/electrospray ionisation source/mass spectrometry (HPLC-ESI-MS). The method was applied during fermentation carried out with Lactobacillus pentosus OM13 (Trial S) and without starter (Trial C). A total of five polyphenols were identified. All samples contained high concentrations of rutin. Epicatechin was found in untreated fruits, on the contrary quercetin was detected during fermentation. Trial S was characterised by a more rapid acidification and lower levels of spoilage microorganisms than Trial C. L. pentosus dominated among the microbial community of both trials and the highest biodiversity, in terms of strains, was displayed by Trial C. Aureobasidium pullulans was the only yeast species found. The analytical method proposed allowed a high polyphenolic compound recovery from untreated and processed caper berries in short time. The starter culture reduced the bitter taste of the final product., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Adjustable mirrors equipped with piezo actuators are commonly used at synchrotron and free-electron laser (FEL) beamlines, in order to optimize their focusing properties and sometimes to shape the intensity distribution of the focal spot with the desired profile. Unlike them, X-ray mirrors for astronomy are much thinner in order to enable nesting and reduce the areal mass, and the application of piezo actuators acting normally to the surface appears much more difficult. There remains the possibility to correct the deformations using thin patches that exert a tangential strain on the rear side of the mirror: some research groups are already at work on this approach. The technique reported here relies on actively integrating thin glass foils with commercial piezoceramic patches, fed by voltages driven by the feedback provided by X-rays, while the tension signals are carried by electrodes on the back of the mirror, obtained by photolithography. Finally, the shape detection and the consequent voltage signal to be provided to the piezoelectric array will be determined by X-ray illumination in an intra-focal setup at the XACT facility. In this work, the manufacturing steps for obtaining a first active mirror prototype are described.

Objective: Knowledge of the cellular mechanisms involved in homeostasis of human squamous oesophagus in the steady state and following chronic injury is limited. We aimed to better understand these mechanisms by using a functional 3D approach., Design: Proliferation, mitosis and the expression of progenitor lineage markers were assessed in normal squamous oesophagus from 10 patients by immunofluorescence on 3D epithelial whole mounts. Cells expressing differential levels of epithelial and progenitor markers were isolated using flow cytometry sorting and characterised by qPCR and IF. Their self-renewing potential was investigated by colony forming cells assays and in vitro organotypic culture models., Results: Proliferation and mitotic activity was highest in the interpapillary basal layer and decreased linearly towards the tip of the papilla (p<0.0001). The orientation of mitosis was random throughout the basal layer, and asymmetric divisions were not restricted to specific cell compartments. Cells sorted into distinct populations based on the expression of epithelial and progenitor cell markers (CD34 and EpCAM) showed no difference in self-renewal in 2D culture, either as whole populations or as single cells. In 3D organotypic cultures, all cell subtypes were able to recapitulate the architecture of the tissue of origin and the main factor determining the success of the 3D culture was the number of cells plated, rather than the cell type., Conclusions: Oesophageal epithelial cells demonstrate remarkable plasticity for self-renewal. This situation could be viewed as an ex vivo wounding response and is compatible with recent findings in murine models., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Introduction: Multiparametric pelvic magnetic resonance imaging (mpMRI) accuracy in prostate cancer (PCa) diagnosis was evaluated., Materials and Methods: From June 2011 to December 2013, 168 patients (median 65 years) with negative digital rectal examination underwent repeat transperineal saturation biopsy (SPBx; median 28 cores) for persistently high or increasing PSA values, PSA >10 ng/ml or PSA values between 4.1-10 o r 2.6-4 ng/ml with free/total PSA < 25% and < 20%, respectively. All patients underwent mpMRI using a 3.0 Tesla scanner equipped with surface 16 channels phased-array coil and lesions suspicious for PCa were submitted to additional targeted biopsies., Results: A T1c PCa was found in 66 (39%) cases; SPBx and mpMRI-suspicious targeted biopsy diagnosed 60 (91%) and 52 (78.8%) cancers missing 6 (all of the anterior zone) and 14 cancers (12 and 2 of the lateral margins and anterior zone), respectively; in detail, mpMRI missed 12 (18.1%) PCa charaterized by microfocal (1 positive core with greatest percentage of cancer and Gleason score equal to 5% and 6, respectively) disease at risk for insignificant cancer. The diameter of the suspicious mpMRI lesion was directly correlated to the diagnosis of PCa with poor Gleason score (p < 0.05); detection rate of cancer for each suspicious mpMRI core was 35.3%. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive value of mpMRI in diagnosing PCa was 75.7%, 82.5%, 71.8%, 78.9%, 87.9%, respectively., Conclusion: Multiparametric pMRI improved SPBx accuracy in diagnosing significant anterior PCa; the diameter of mpMRI suspicious lesion resulted significantly predictive of aggressive cancers.

Cancer genome sequencing studies have identified numerous driver genes, but the relative timing of mutations in carcinogenesis remains unclear. The gradual progression from premalignant Barrett's esophagus to esophageal adenocarcinoma (EAC) provides an ideal model to study the ordering of somatic mutations. We identified recurrently mutated genes and assessed clonal structure using whole-genome sequencing and amplicon resequencing of 112 EACs. We next screened a cohort of 109 biopsies from 2 key transition points in the development of malignancy: benign metaplastic never-dysplastic Barrett's esophagus (NDBE; n=66) and high-grade dysplasia (HGD; n=43). Unexpectedly, the majority of recurrently mutated genes in EAC were also mutated in NDBE. Only TP53 and SMAD4 mutations occurred in a stage-specific manner, confined to HGD and EAC, respectively. Finally, we applied this knowledge to identify high-risk Barrett's esophagus in a new non-endoscopic test. In conclusion, mutations in EAC driver genes generally occur exceptionally early in disease development with profound implications for diagnostic and therapeutic strategies.

Aim: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and locally aggressive tumor with poor prognosis, related in most cases to asbestos exposure. It is increasing in frequency, but currently no standard therapy is available. The biology of this disease is still poorly understood. Several highly specialized centers have recently reported improved survival by means of an innovative local-regional approach. The purpose of this article is to evaluate the survival benefit and the morbidity rate of patients affected by DMPM treated at our institution by cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal perioperative chemotherapy (HIPEC)., Methods: This study includes 42 patients affected by DMPM treated by an uniform approach consisting of cytoreductive surgery associated with HIPEC using cisplatin and doxorubicin. The primary end point was overall survival and morbidity rate. The secondary end point was evaluation of prognostic variables for overall survival., Results: The median follow-up period was 72 months (range 1-235 months). Thirty-five patients (83.3%) presented epithelial tumors and 7 were affected by multicystic mesothelioma. The mean peritoneal cancer index (PCI) was 13. Thirty-eight patients (90.4%) had complete cytoreduction (CC-0/1). The overall morbidity rate was 35.7% associated to a perioperative mortality of 7.1%. Median overall survival rate was 65 months with a 1- and 5-year survival rates of 63% and 44%, respectively., Conclusion: The treatment of DMPM by CRS+HIPEC in selected patients is a feasible technique that allows to achieve encouraging results in terms of overall survival rate, with an acceptable morbidity rate. Further investigations are needed to clarify the role and the timing of this promising technique.

Introduction: The aim of the study was to compare the sensory, motor, and neuroophthalmological effects of isobaric levobupivacaine and bupivacaine when intrathecally administered., Materials and Methods: A prospective, double-blind, randomized study with 60 ASA grade I-II patients aged 18-65 years awaiting knee arthroscopy under spinal anesthesia. Patients received 12.5 mg of isobaric bupivacaine or levobupivacaine. Several features were recorded., Results: No significant intergroup differences were observed for ASA classification, time to micturate, demographic data, surgery duration, and patient/surgeon satisfaction. Similar hemodynamic parameters and sensory/motor blockade duration were found for both groups. There were no neuroophthalmological effects in either group. Sensory (P = 0.018) and motor blockade onset (P = 0.003) was faster in the bupivacaine group. T6 (T2-T12) and T3 (T2-T12) were the highest sensory block levels for the levobupivacaine and bupivacaine groups, respectively (P = 0.008). It took less time to regain maximum motor blockade in the bupivacaine group (P = 0.014), and the levobupivacaine group required use of analgesia earlier (P = 0.025)., Conclusions: Isobaric bupivacaine and levobupivacaine are analogous and well-tolerated anesthetics for knee arthroscopy. However, for bupivacaine, sensory and motor blockade onset was faster, and greater sensory blockade with a longer postoperative painless period was achieved.

Background: MicroRNAs (miRNAs) are a class of small, well-conserved, non-coding RNAs that regulate the translation of RNAs. They have a role in biological and pathological process including cell differentiation, apoptosis, proliferation and metabolism. Since their discovery, they have been shown to have a potential role in cancer pathogenesis through their function as oncogenes or tumor suppressors. A substantial number of miRNAs show differential expression in esophageal cancer tissues, and so have been investigated for possible use in diagnosis. Furthermore, there is increasing interest in their use as prognostic markers and determining treatment response, as well as identifying their downstream targets and understanding their mode of action., Methods: We analyzed the most recent studies on miRNAs in esophageal cancer and/or Barrett's esophagus (BE). The publications were identified by searching in PuBMed for the following terms: Barrett's esophagus and microRNA; esophageal cancer and microRNA., Results: Four miRNAs (mi-R-25, -99a, -133a and -133b) showed good potential as diagnostic markers and interestingly five (mi-R-21, -27b, -126, - 143 and -145) appeared to be useful both as diagnostic and prognostic/predictive markers., Conclusion: The data so far on miRNAs in esophageal carcinogenesis is promising but further work is required to determine whether miRNAs can be used as biomarkers, not only in the clinical setting or added to individualized treatment regimes but also in non-invasive test by making use of miRNAs identified in blood., (Copyright © 2013. Published by Elsevier Ltd.)

Homology-directed repair (HDR) is a critical pathway for the repair of DNA double-strand breaks (DSBs) in mammalian cells. Efficient HDR is thought to be crucial for maintenance of genomic integrity during organismal development and tumor suppression. However, most mammalian HDR studies have focused on transformed and immortalized cell lines. We report here the generation of a Direct Repeat (DR)-GFP reporter-based mouse model to study HDR in primary cell types derived from diverse lineages. Embryonic and adult fibroblasts from these mice as well as cells derived from mammary epithelium, ovary, and neonatal brain were observed to undergo HDR at I-SceI endonuclease-induced DSBs at similar frequencies. When the DR-GFP reporter was crossed into mice carrying a hypomorphic mutation in the breast cancer susceptibility gene Brca1, a significant reduction in HDR was detected, showing that BRCA1 is critical for HDR in somatic cell types. Consistent with an HDR defect, Brca1 mutant mice are highly sensitive to the cross-linking agent mitomycin C. By contrast, loss of the DSB signaling ataxia telangiectasia-mutated (ATM) kinase did not significantly alter HDR levels, indicating that ATM is dispensable for HDR. Notably, chemical inhibition of ATM interfered with HDR. The DR-GFP mouse provides a powerful tool for dissecting the genetic requirements of HDR in a diverse array of somatic cell types in a normal, nontransformed cellular milieu.

Introduction: To evaluate PCA3 score accuracy in prostate cancer (PCa) diagnosis in patients undergoing repeat saturation prostate biopsy (SPBx)., Material and Methods: From January 2010 to March 2012, 177 patients (median 64 years) with primary negative extended biopsy underwent a SPBx (median 28 cores) for persistent suspicion of PCa. The indications for repeat biopsy were: PSA > 10 ng/mL, PSA values between 4.1-10 or 2.6-4 ng/mL with free/total PSA < 25% and < 20%, respectively; moreover, before performing SPBx PCA3 score was evaluated., Results: Median PSA was 9.5 ng/mL (range: 3.7-28 ng/mL): in 74 (41.8%) cases PSA was > 10 ng/mL, in 99 (56%) and 4 (2.2%) was included between 4-10 and 2.6-4 ng/mL, respectively. Median PCA3 score was equal to 52 (range 3-273); 140 (79%) and 100 (56.5%) patients had a PCA3 score greater than 20 and 35, respectively. A T1c PCa was found in 48 patients (27.1%); PCA3 score was 60 (median; range: 7-208) in the presence of PCa and 34 (median; range: 3-268) in the absence of cancer (p < 0.05). Diagnostic accuracy, sensitivity, specificity, PPV and NPV of PCA3 score cut-off of 20 vs. 35 in PCa diagnosis were 43.5 vs. 50.2%, 91.7 vs. 73%, 25.6 vs. 41.8%, 31.5 vs. 35% and 89.5 vs. 80.6%, respectively., Conclusions: PCA3 score reduce number of unnecessary repeat SPBx; using a PCA3 cut-off of 20 vs 35 would have avoided 21% vs. 37.8% of biopsies while missing 8.4% (4 cases) vs. 27% (13 cases) of significant PCa, respectively.

From the beginning of 2007 until the end of 2011, 146 cases of lymphogranuloma venereum (LGV) were notified to the Barcelona Public Health Agency. Some 49% of them were diagnosed and reported in 2011, mainly in men who have sex with men. Almost half of them, 32 cases, were reported between July and September. This cluster represents the largest since 2004. This article presents the ongoing outbreak of LGV in Barcelona.

The antigenic structure of Treponema pallidum was described in the 1940s and 1950s. The main contributions of Giuseppe D'Alessandro and his collaborators included the description of the external membrane and of the polysaccharide antigen found in the cell wall of the microorganism. Based on new knowledge it has been possible to develop diagnostic tests that are more sensitive and specific than nontreponemal tests, which nevertheless retain their validity in the current re-emergence of syphilis as a public health problem.

Objectives: To evaluate PCa incidence in patients with one or more negative extended prostate biopsy who underwent repeat biopsy or TURP., Material and Methods: From June 2003 to February 2008, 308 patients were submitted to repeat prostate biopsy (median 20.5 cores) and 120 patients underwent TURP after one or more 12 cores prostate biopsy. Indications for biopsy were: abnormal DRE; PSA > 10 ng/mL; PSA included between 4.1-10 or 2.6-4 ng/mL with free/total PSA < or = 25% and < or = 20%, respectively 262 and 46 underwent a second and a third biopsy: 218 because for high levels of PSA, 40 and 50 patients for a previous diagnosis of HGPIN and ASAP, 28 had an abnormal DRE. PSA in patients who underwent TURP was 11.6 ng/mL (median); in all cases DRE was negative and only 76 patients referred LUTS., Results: PCa incidence at repeat biopsy was 16.9%; 96.2% of cancers were diagnosed at a second biopsy and 3.8% at a third one. PCa incidence was higher in patients with previous ASAP (43.4% and 50%) vs patients with HGPIN (25% and 0%) or benign pathology (11.9% and 0%). PCa was diagnosed in 11.1% and 19% of patients who underwent TURP previously submitted to a first and a second biopsy, respectively., Conclusions: In case of persistent suspicion of PCa after a repeated negative saturation biopsy, TURP should be proposed as part of the diagnostic procedure aside from LUTS, especially in patients with a life expectancy greater than 10 years.