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Solid-state supercapacitors with areal capacitance in the order of 100 mF⋅cm -2 are developed on paper substrates, using eco-friendly, low-cost materials and a simple technology. The electrochemically active material used as the electrode is prepared from a stable water-based ink, obtained by doping commercial polypyrrole (PPY) powder with dodecylbenzene sulfonic acid (DBSA), and characterized by optical and electrical measurements, Raman investigation and Atomic Force Microscopy. The PPY:DBSA ink can be directly applied on paper by means of rechargeable water pens, obtaining, after drying, electrically conducting solid state tracks. The PPY:DBSA layers are then interfaced to one another through a polymer gel based on potassium hydroxide and chitosan, acting both as the ion-conducting medium and as the separator. The areal capacitance of the devices developed by following such a simple rule can be improved when the PPY:DBSA ink is applied in combination with other nanostructured carbon material.

Introduction: Low molecular weight heparin (LMWH) has been the backbone of the treatment of cancer associated thrombosis (CAT). Direct-acting oral anticoagulants (DOACs) have shown efficacy and safety not inferior to LMWH and guidelines included DOACs as an option for CAT treatment. Nevertheless, DOACs are still poorly prescribed in patients with cancer. The aim of this survey was to better understand prescription patterns of anticoagulants, in particular of DOACs, especially in gynecological cancers (GCs)., Methods: Our survey was made up of 21 questions, the last four questions addressed to medical doctors (MDs) involved in GCs. An invitation to complete the survey was sent by e-mail to 691 MITO (Multicentre Italian Trials in Ovarian cancer and gynaecologic malignancies) and 2093 AIOM (Associazione Italiana di Oncologia Medica) members., Results: Overall, 113 MDs completed the questionnaire, 69 involved in GCs. Most respondents (46, 41%) were aged 30-40 years old, worked in public hospitals (59, 52.2%), were medical oncologists (86, 76.1%). LMWH was the preferred choice for the treatment of CAT (104, 92%). However, 89 respondents (78.8%) prescribed or asked to prescribe a DOAC for CAT. The major concern about DOACs was the difficulty in verifying the therapeutic effect and the absence of antidotes in case of bleeding (37.9%). In patients with GCs, DOACs were used with niraparib, olaparib, rucaparib and immune checkpoint inhibitors (ICIs) in less than 10 patients by 23%, 20%, 9% and 10.2% of respondents, respectively., Conclusion: The responders are aware of the Direct-acting oral anticoagulants option and would like to use them.

The Internet of Things (IoT) is gaining more and more popularity and it is establishing itself in all areas, from industry to everyday life. Given its pervasiveness and considering the problems that afflict today's world, that must be carefully monitored and addressed to guarantee a future for the new generations, the sustainability of technological solutions must be a focal point in the activities of researchers in the field. Many of these solutions are based on flexible, printed or wearable electronics. The choice of materials therefore becomes fundamental, just as it is crucial to provide the necessary power supply in a green way. In this paper we want to analyze the state of the art of flexible electronics for the IoT, paying particular attention to the issue of sustainability. Furthermore, considerations will be made on how the skills required for the designers of such flexible circuits, the features required to the new design tools and the characterization of electronic circuits are changing.

Background: Platinum-based chemotherapy (PBCT) is the standard first-line treatment for advanced urothelial carcinoma (UC). Potential cross-sensitivity can be hypothesized between platinum drugs and poly-ADP ribose-polymerase (PARP) inhibitors., Objective: To compare maintenance treatment with the PARP inhibitor niraparib plus best supportive care (BSC) versus BSC alone in patients with advanced UC without disease progression after first-line PBCT., Design, Setting, and Participants: Meet-URO12 is a randomized, multicenter, open-label phase 2 trial. Patients with advanced UC, without disease progression after four to six cycles of PBCT, with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, were enrolled between August 2019 and March 2021. Randomization was stratified by ECOG performance status (0/1) and response to PBCT (objective response/stable disease)., Intervention: Patients were randomized (2:1) to experimental arm A (niraparib 300 or 200 mg daily according to body weight and baseline platelets, plus BSC) or control arm B (BSC alone)., Outcome Measurements and Statistical Analysis: The primary endpoint was progression-free survival (PFS). The analysis was performed on an intention-to-treat basis. The secondary endpoints reported in this primary analysis are progression-free rate at 6 mo and safety (adverse event rate)., Results and Limitations: Fifty-eight patients were randomized (39 in arm A and 19 in arm B). The median age was 69 yr, ECOG performance status was 0 in 66% and 1 in 34%; and the best response with chemotherapy was objective response in 55% and stable disease in 45%. The median PFS was 2.1 mo in arm A and 2.4 mo in arm B (hazard ratio 0.92; 95% confidence interval 0.49-1.75, p = 0.81). The 6-mo progression-free rates were 28.2% and 26.3%, respectively. The most common adverse events with niraparib were anemia (50%, grade [G]3 11%), thrombocytopenia (37%, G3-4 16%), neutropenia (21%, G3 5%), fatigue (32%, G3 16%), constipation (32%, G3 3%), mucositis (13%, G3 3%), and nausea (13%, G3 3%). The main limitation of the study is the small sample size: in March 2021, approval of maintenance avelumab for the same setting rendered randomization of patients in the control arm to BSC alone unethical, and accrual was stopped prematurely., Conclusions: Addition of maintenance niraparib to BSC after first-line PBCT did not demonstrate a significant improvement in PFS in patients with UC. These results do not support the conduction of a phase 3 trial with single agent niraparib in this population., Patient Summary: In this trial, we tested the efficacy of niraparib as maintenance treatment in patients affected by advanced urothelial cancer after the completion of first-line chemotherapy. We could not demonstrate a significant improvement in progression-free survival with maintenance niraparib., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Metastatic breast cancer (MBC) is an incurable disease and its treatment focuses on prolonging patients' (pts) overall survival (OS) and improving their quality of life. Eribulin is a microtubule inhibitor that increases OS in pre-treated MBC pts. The most common adverse events (AEs) are asthenia, neutropenia and peripheral neuropathy (PN)., Methods: PAINTER is a single arm, phase IV study, aimed at evaluating the tolerability of eribulin in MBC pts. Secondary objectives were the description of treatment efficacy and safety, the assessment of the incidence and severity of PN and its association with genetic polymorphisms. Genomic DNA was isolated from blood samples and 15 Single Nucleotide Polymorphisms (SNPs) were genotyped by Taqman specific assays. The association between PN and SNPs were evaluated by Fisher exact test., Results: Starting from May 2014 until June 2018 180 pts were enrolled in this study by 20 Italian centers. 170 of these pts could be evaluated for efficacy and toxicity and 159 for polymorphisms analysis. The median age of pts was 60 years old and the biological subtypes were luminal type (64.7%), Her2 positive (18.3%) and triple negative (17%). Pts were pretreated with a median of 5 lines for MBC. The median follow up of this study was 15.4 months with a median number of 4.5 cycles administered (minimum-maximum 1-23). The median overall survival was 12 months. 48.8% of pts experienced a dose reduction, mainly for neutropenia (23.9%) and liver toxicity (12%). 65 pts (38.2%) reported at least one severe toxicity. Neutropenia and neurotoxicity were the most frequent severe AEs (15.3% and 14.7%, respectively); other reported toxicities were osteo-muscular, abdominal or tumor site pain (19.4%), liver toxicity (6.6%), pulmonary toxicity (6.5%) and dermatological toxicity (3.6%). Among the 15 evaluated SNPs, an association with PN was found for rs2233335 and rs7214723., Conclusions: Eribulin is a well-tolerated treatment option in MBC. Schedule and dosage modifications were common, but toxicity rarely led to treatment discontinuation. SNPs rs2233335 (G/T and T/T) in the NDRG1 gene and rs7214723 (CC and CT) in the CAMKK1 gene were associated with PN. These findings, if validated, could allow a tailored treatment with eribulin in cancer patients., Trial Registration: ClinicalTrials.gov ID: NCT02864030., (© 2022. The Author(s).)

Achieving homogenous dispersion of nanoparticles inside a polymeric matrix is a great challenge for numerous applications. In the present study, we aim at understanding the role of different factors on the dispersion properties of TiO 2 in pluronic F-127 mixtures. The mixtures were prepared with different pH and guest/host ratios and investigated by UV-Vis spectroscopy, dynamic light scattering, infrared spectroscopy and electrical conductivity. Depending on the preparation conditions, different amounts of TiO 2 were loaded within the copolymer as quantitatively determined by UV-Vis spectroscopy. The different content of nanoparticles has direct implications on the gelation and micellization of pluronic analyzed by dynamic light scattering. The information derived on the self-assembly behavior was interpreted in relation to the infrared and conductivity measurements results. Together, these results shed light on the most favorable conditions for improving the nanoparticle dispersion inside the copolymer matrix and suggest a possible strategy to design functional nanoparticle-polymer systems.

The COVID-19 pandemic is manifesting its devastating effects in multiple directions, even indirectly affecting the health of citizens, for instance, by increasing the level of energy poverty (EP). As part of the studies that are trying to frame the consequences of the pandemic, this paper aims to identify the effects on EP in the coming years in a bid to identify the countries of the European Union most affected and the time span necessary to return to a path to reduce EP. For this purpose, an analysis based on the supervised learning algorithms of dynamic factor models is carried out. The outcomes of this investigation show that the negative effects of the pandemic on the level of EP will be reabsorbed very slowly, not before 2025, and in any case with substantial differences between countries, further widening the gap between countries with low levels of EP and those with greater EP levels., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Elsevier Ltd. All rights reserved.)

Flexible energy storage devices and supercapacitors in particular have become very attractive due to the growing demand for wearable consumer devices. To obtain supercapacitors with improved performance, it is useful to resort to hybrid electrodes, usually nanocomposites, that combine the excellent charge transport properties and high surface area of nanostructured carbon with the electrochemical activity of suitable metal oxides or conjugated polymers. In this work, electrochemically active conducting inks are developed starting from commercially available polypyrrole and graphene nanoplatelets blended with dodecylbenzenesulfonic acid. Films prepared by applying the developed inks are characterized by means of Raman measurements, Fourier Transform Infrared (FTIR) analysis, and Atomic Force Microscopy (AFM) investigations. Planar supercapacitor prototypes with an active area below ten mm 2 are then prepared by applying the inks onto transparency sheets, separated by an ion-permeable nafion layer impregnated with lithium hexafluorophospate, and characterized by means of electrical measurements. According to the experimental results, the devices show both pseudocapacitive and electric double layer behavior, resulting in areal capacitance that, when obtained from about 100 mF⋅cm -2 in the sample with polypyrrole-based electrodes, increases by a factor of about 3 when using electrodes deposited from inks containing polypyrrole and graphene nanoplateles.

Introduction: The role of cytoreductive surgery in the poly-ADP ribose polymerase inhibitors era is not fully investigated. We evaluated the impact of surgery performed prior to platinum-based chemotherapy followed by olaparib maintenance in platinum-sensitive BRCA-mutated recurrent ovarian cancer., Methods: This retrospective study included platinum-sensitive recurrent ovarian cancer BRCA-mutated patients from 13 Multicenter Italian Trials in Ovarian cancer and gynecological malignancies centers treated between September 2015 and May 2019. The primary outcomes were progression-free survival and overall survival. Data on post-progression treatment was also assessed., Results: Among 209 patients, 72 patients (34.5%) underwent cytoreductive surgery followed by platinum-based chemotherapy and olaparib maintenance, while 137 patients (65.5%) underwent chemotherapy treatment alone. After a median follow-up of 37.3 months (95% CI: 33.4 to 40.8), median progression-free survival in the surgery group was not reached, compared with 11 months in patients receiving chemotherapy alone (P<0.001). Median overall survival was nearly double in patients undergoing surgery before chemotherapy (55 vs 28 months, P<0.001). Post-progression therapy was assessed in 127 patients: response rate to chemotherapy was 29.2%, 8.8%, and 9.0% in patients with platinum-free interval >12 months, between 6 and 12 months, and <6 months, respectively., Conclusion: Cytoreductive surgery performed before platinum therapy and olaparib maintenance was associated with longer progression-free survival and overall survival in BRCA-mutated platinum-sensitive relapsed ovarian cancer patients. In accordance with our preliminary results, the response rate to chemotherapy given after progression during olaparib was associated with platinum-free interval., Competing Interests: Competing interests: VS has been part of advisory boards of GSK, PharmaMar, Roche, MSD, EISAI, Clovis, AstraZeneca. DL reports personal financial interests (advisory roles) with AstraZeneca, Biocad, Clovis Oncology, Genmab, Merck, MSD, Roche, Tesaro-GSK, Amgen, Immunogen, Pharmamar, and institutional financial interests (Study Grants) with AstraZeneca, Clovis Oncology, MSD, Tesaro-GSK, Pharmamar, Roche. Others Global Clinical Lead ENGOT-CX11 Pembrolizumab; Board of Directors, GCIG (Gynecologic Cancer Inter Group). CM reports an advisory role for GSK, Arquer Diagnostic, Pharmamar, Clovis Oncology, and travel grant from Roche. FR reports honoraria from GSK, Pharmamar, Clovis, MSD as sponsors for meetings. GV is an advisor for AstraZeneca, GSK, Amgen, and received speaking honoraria from AstraZeneca, GSK, Roche, Pharmamar. GS reports honoraria from AstraZeneca, MSD, Roche, Clovis, GSK, Pharmamar, Roche (advisory role), and received institutional financial interest (study grants) from AstraZeneca, MSD, GSK, Pharmamar, and he is a member of the board of the National Health Institute. SP reports honoraria from AstraZeneca, MSD, Roche Clovis, GSK Pfizer Pharmamar., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Ovarian cancer represents one of the most aggressive female tumors worldwide. Over the decades, the therapeutic options for the treatment of ovarian cancer have been improved significantly through the advancement of surgical techniques as well as the availability of novel effective drugs able to extend the life expectancy of patients. However, due to its clinical, biological and molecular complexity, ovarian cancer is still considered one of the most difficult tumors to manage. In this context, several studies have highlighted how a multidisciplinary approach to this pathology improves the prognosis and survival of patients with ovarian cancer. On these bases, the aim of the present review is to present recent advantages in the diagnosis, staging and treatment of ovarian cancer highlighting the benefits of a patient‑centered care approach and on the importance of a multidisciplinary team for the management of ovarian cancer.

The main requirement for using the Fluctuation Enhanced Sensing technique is the ability to perform low-frequency noise measurements. The portability of the measurement system is also a quite desirable feature not limited to this specific application. In this paper, an approach for the realization of a dual channel spectrum analyzer that is capable of exploring frequencies down to DC, although based on a USB sound card, is proposed. The lower frequency range of the input signals, which is outside the frequency range of the sound board, is upconverted to higher frequencies by means of a very simple modulation board. Then, the entire spectrum is reconstructed numerically by proper elaboration. With the exception of the modulation board, the approach we propose does not rely on any specific hardware. Thanks to the efficiency of the spectra estimation and reconstruction software, which is based on a public domain library, the system can be built on a low-cost computer single board computer, such as the Raspberry PI3. Moreover, when equipped with an optical TCP/IP link, it behaves as a compact spectrum analyzer that along with the device under test can be placed into a shielded environment, thus being isolated from external electromagnetic interferences.

The severe acute respiratory syndrome associated coronavirus‑2 (SARS‑CoV‑2) poses a threat to human life worldwide. Since early March, 2020, coronavirus disease 2019 (COVID‑19), characterized by an acute and often severe form of pneumonia, has been declared a pandemic. This has led to a boom in biomedical research studies at all stages of the pipeline, from the in vitro to the clinical phase. In line with this global effort, known drugs, currently used for the treatment of other pathologies, including antivirals, immunomodulating compounds and antibodies, are currently used off‑label for the treatment of COVID‑19, in association with the supportive standard care. Yet, no effective treatments have been identified. A new hope stems from medical oncology and relies on the use of immune‑checkpoint inhibitors (ICIs). In particular, amongst the ICIs, antibodies able to block the programmed death‑1 (PD‑1)/PD ligand-1 (PD‑L1) pathway have revealed a hidden potential. In fact, patients with severe and critical COVID‑19, even prior to the appearance of acute respiratory distress syndrome, exhibit lymphocytopenia and suffer from T‑cell exhaustion, which may lead to viral sepsis and an increased mortality rate. It has been observed that cancer patients, who usually are immunocompromised, may restore their anti‑tumoral immune response when treated with ICIs. Moreover, viral-infected mice and humans, exhibit a T‑cell exhaustion, which is also observed following SARS‑CoV‑2 infection. Importantly, when treated with anti‑PD‑1 and anti‑PD‑L1 antibodies, they restore their T‑cell competence and efficiently counteract the viral infection. Based on these observations, four clinical trials are currently open, to examine the efficacy of anti‑PD‑1 antibody administration to both cancer and non‑cancer individuals affected by COVID‑19. The results may prove the hypothesis that restoring exhausted T‑cells may be a winning strategy to beat SARS‑CoV‑2 infection.

Healthy lifestyles are associated with better health-related quality of life (HRQoL), favorable prognosis and lower mortality in breast cancer (BC) survivors. We investigated changes in HRQoL after a 12-month lifestyle modification program in 227 BC survivors participating in DEDiCa trial (Mediterranean diet, exercise, vitamin D). HRQoL was evaluated through validated questionnaires: EQ-5D-3L, EORTC-QLQ-C30 and EORTC QLQ-BR23. Baseline changes were tested using analysis of variance. Multiple regression analyses were performed to assess treatment effects on HRQoL. Increases were observed in global health status ( p < 0.001), physical ( p = 0.003), role ( p = 0.002) and social functioning ( p < 0.001), body image ( p < 0.001), future perspective ( p < 0.001), well-being ( p = 0.001), and reductions in fatigue ( p < 0.001), nausea and vomiting ( p = 0.015), dyspnea ( p = 0.001), constipation ( p = 0.049), financial problems ( p = 0.012), sexual functioning ( p = 0.025), systematic therapy side effects ( p < 0.001) and breast symptoms ( p = 0.004). Multiple regression analyses found inverse associations between changes in BMI and global health status ( p = 0.048) and between serum 25(OH)D levels and breast symptoms ( p = 0.002). A healthy lifestyle treatment of traditional Mediterranean diet and exercise may impact positively on HRQoL in BC survivors possibly through reductions in body weight while vitamin D sufficiency may improve BC-related symptoms. These findings are relevant to BC survivors whose lower HRQoL negatively affects treatment compliance and disease outcomes.

Evidence suggests a beneficial role of the Mediterranean Diet (MedDiet) on health-related quality of life (HRQoL) in healthy subjects. HRQoL is relevant in cancer therapy and disease outcomes, therefore we investigated the association between adherence to the MedDiet and HRQoL in breast cancer survivors participating in the multicentre trial DEDiCa. Diet and HRQoL were assessed at baseline in a subgroup of 309 women enrolled within 12 months of breast cancer diagnosis without metastasis (stages I-III, mean age 52±1 yrs, BMI 27±7 kg/m2). The 14-item PREDIMED questionnaire was used to analyse adherence to the MedDiet. HRQoL was assessed with three validated questionnaires measuring physical, mental, emotional and social factors: EQ-5D-3L, EORTC QLQ-C30 and EORTC QLQ-BR23. Analysis of variance (ANOVA) and multivariate analyses were performed to assess the possible role of the MedDiet on HRQoL. Patients with higher adherence to MedDiet (PREDIMED score >7) showed significantly higher scores for physical functioning (p = 0.02) and lower scores on the symptomatic pain scale (p = 0.04) assessed by the EORTC QLQ-C30 questionnaire compared to patients with a lower adherence to MedDiet (PREDIMED score ≤7). Higher scores from the EQ-5D-3L indicating higher well-being were observed mainly in participants with higher MedDiet adherence (p = 0.05). In adjusted multivariate analyses significant positive associations were found between MedDiet, physical functioning (p = 0.001) and EQ 5D-3L score (p = 0.003) while inverse associations were found with pain and insomnia symptoms (p = 0.005 and p = 0.029, respectively). These results suggest that higher adherence to the MedDiet in breast cancer survivors is associated with better aspects of quality of life, specifically higher physical functioning, better sleep, lower pain and generally higher well-being confirming findings in healthy subjects., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: LSAA is a founding member of the International Carbohydrate Quality Consortium (ICQC) and has received honoraria from the Nutrition Foundation of Italy (NFI), research grants from LILT (a non-profit organization for the fight against cancer) and in-kind research support from Abiogen Pharma, the Almond Board of California (USA), Barilla (Italy), Consorzio Mandorle di Avola (Italy), DietaDoc (Italy), Ello Frutta (Italy), Panificio Giacomo Luongo (Italy), Perrotta (Italy), Roberto Alimentare (Italy), SunRice (Australia). However, no funding that she has received has been involved in the current project. GLB reports personal fees from Janssen-Cilag, personal fees from Boehringer Ingelheim, personal fees from Roche, non-financial support from Bristol-Myers Squibb, non-financial support from AstraZeneca/MedImmune, non-financial support from Pierre Fabre, non-financial support from Ipsen, outside the submitted work. DG has received speaking and/or consulting fees from Abiogen Pharma, Amgen, Eli-Lilly, Janssen-Cilag, Merck and Mundipharma. MP has received research support from Amgen. GR has received research grants from the Barilla Company to his University Department and is member of the scientific advisory boards of the foundation “Barilla Center for Food and Nutrition” and of “Nutrition Foundation of Italy”. DJAJ has received research grants from Saskatchewan & Alberta Pulse Growers Associations, the Agricultural Bioproducts Innovation Program through the Pulse Research Network, the Advanced Foods and Material Network, Loblaw Companies Ltd., Unilever Canada and Netherlands, Barilla, the Almond Board of California, Agriculture and Agri-food Canada, Pulse Canada, Kellogg’s Company, Canada, Quaker Oats, Canada, Procter & Gamble Technical Centre Ltd., Bayer Consumer Care, Springfield, NJ, Pepsi/Quaker, International Nut & Dried Fruit (INC), Soy Foods Association of North America, the Coca-Cola Company (investigator initiated, unrestricted grant), Solae, Haine Celestial, the Sanitarium Company, Orafti, the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Soy Nutrition Institute (SNI), the Canola and Flax Councils of Canada, the Calorie Control Council, the Canadian Institutes of Health Research (CIHR), the Canada Foundation for Innovation (CFI)and the Ontario Research Fund (ORF). He has received in-kind supplies for trials as a research support from the Almond board of California, Walnut Council of California, American Peanut Council, Barilla, Unilever, Unico, Primo, Loblaw Companies, Quaker (Pepsico), Pristine Gourmet, Bunge Limited, Kellogg Canada, WhiteWave Foods. He has been on the speaker’s panel, served on the scientific advisory board and/or received travel support and/or honoraria from the Almond Board of California, Canadian Agriculture Policy Institute, Loblaw Companies Ltd, the Griffin Hospital (for the development of the NuVal scoring system), the Coca-Cola Company, EPICURE, Danone, Diet Quality Photo Navigation (DQPN), Better Therapeutics (FareWell), Verywell, True Health Initiative (THI), Heali AI Corp, Institute of Food Technologists (IFT), Soy Nutrition Institute (SNI), Herbalife Nutrition Institute (HNI), Saskatchewan & Alberta Pulse Growers Associations, Sanitarium Company, Orafti, the American Peanut Council, the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Herbalife International, Pacific Health Laboratories, Nutritional Fundamentals for Health (NFH), Barilla, Metagenics, Bayer Consumer Care, Unilever Canada and Netherlands, Solae, Kellogg, Quaker Oats, Procter & Gamble, Abbott Laboratories, Dean Foods, the California Strawberry Commission, Haine Celestial, PepsiCo, the Alpro Foundation, Pioneer Hi-Bred International, DuPont Nutrition and Health, Spherix Consulting and WhiteWave Foods, the Advanced Foods and Material Network, the Canola and Flax Councils of Canada, Agri-Culture and Agri-Food Canada, the Canadian Agri-Food Policy Institute, Pulse Canada, the Soy Foods Association of North America, the Nutrition Foundation of Italy (NFI), Nutra-Source Diagnostics, the McDougall Program, the Toronto Knowledge Translation Group (St. Michael’s Hospital), the Canadian College of Naturopathic Medicine, The Hospital for Sick Children, the Canadian Nutrition Society (CNS), the American Society of Nutrition (ASN), Arizona State University, Paolo Sorbini Foundation and the Institute of Nutrition, Metabolism and Diabetes. He received an honorarium from the United States Department of Agriculture to present the 2013 W.O. Atwater Memorial Lecture. He received the 2013 Award for Excellence in Research from the International Nut and Dried Fruit Council. He received funding and travel support from the Canadian Society of Endocrinology and Metabolism to produce mini cases for the Canadian Diabetes Association (CDA). He is a member of the International Carbohydrate Quality Consortium (ICQC). His wife, Alexandra L Jenkins, is a director and partner of INQUIS Clinical Research for the Food Industry, his 2 daughters, Wendy Jenkins and Amy Jenkins, have published a vegetarian book that promotes the use of the foods described here, The Portfolio Diet for Cardiovascular Risk Reduction (Academic Press/Elsevier 2020 ISBN:978-0-12-810510-8) and his sister, Caroline Brydson, received funding through a grant from the St. Michael’s Hospital Foundation to develop a cookbook for one of his studies. He has had close contact with the food industry to produce plant based diets. However, no funding that he has received has been involved in the current project. All other authors declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Tuberculosis (TB) is the leading infectious cause of human mortality and is responsible for nearly 2 million deaths every year. It is often regarded as a 'silent killer' because it predominantly affects the poor and marginalized, and disease outbreaks occur in 'slow motion' compared to Ebola or coronavirus 2 (COVID-19). In low incidence countries, TB is predominantly an imported disease and TB control in migrants is pivotal for countries to progress towards TB elimination in accordance with the World Health Organisations (WHO's) End TB strategy. This review provides a brief overview of the different screening approaches and surveillance processes that are in place in low TB incidence countries. It also includes a detailed discussion of the ethical issues related to TB screening of migrants in these settings and the different interests that need to be balanced. Given recognition that a holistic approach that recognizes and respects basic human rights is required to end TB, the review considers the complexities that require consideration in low-incidence countries that are aiming for TB elimination., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

The coronavirus disease 2019 (COVID-19) is currently representing a global health threat especially for fragile individuals, such as cancer patients. It was demonstrated that cancer patients have an increased risk of developing a worse symptomatology upon severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) infection, often leading to hospitalization and intensive care. The consequences of this pandemic for oncology are really heavy, as the entire healthcare system got reorganized. Both oncologists and cancer patients are experiencing rescheduling of treatments and disruptions of appointments with a concurrent surge of fear and stress. In this review all the up-to-date findings, concerning the association between COVID-19 and cancer, are reported. A remaining very debated question regards the use of an innovative class of anti-cancer molecules, the immune checkpoint inhibitors (ICIs), given their modulating effects on the immune system. For that reason, administration of ICIs to cancer patients represents a question mark during this pandemic, as its correlation with COVID-19-associated risks is still under investigation. Based on the mechanisms of action of ICIs and the current evidence, we suggest that ICIs not only can be safely administered to cancer patients, but they might even be beneficial in COVID-19-positive cancer patients, by exerting an immune-stimulating action.

Olaparib is the first poly(ADP-ribose) polymerase inhibitor approved as maintenance therapy of recurrent ovarian cancer (OC) patients with a BRCA mutation. To achieve the maximum clinical benefit, adherence to olaparib must be persistent. However, in clinical practice, this is challenged by the frequent suboptimal management of toxicities. In view of the expanding use of olaparib also in Italy, physicians must learn how to adequately and promptly manage drug toxicities not to unnecessarily interrupt or reduce the dose. The experts agreed that nausea,vomiting, anemia, and fatigue are the most frequent events experienced by OC patients on olaparib, and that these toxicities usually develop early during treatment, are mainly of grade 1-2 and transient and can be managed with simple non-pharmacological interventions. By sharing their real-world experiences, the panel prepared, for each toxicity, an algorithm organized by grade and besides the procedures indicated in the local label, included supportive care interventions based also on nutritional and lifestyle modifications and psycho-oncology consultation. Moreover, in view of the tablet entry into the Italian market, the full and reduced dosages of capsules and tablets were compared. This practical guidance is intended to be a tool to support especially less-experienced physicians in the management of these complex patients, with the aim to help preventing the worsening of patients' conditions and the unnecessary interruption/reduction of olaparib dosage, which may jeopardize treatment efficacy.

Objectives: Olaparib is approved as maintenance therapy in patients with BRCA mutated platinum sensitive (PS) recurrent ovarian cancer (OC) after response to last platinum based therapy. Few data are available regarding the use out of the registration trials and on response to further treatments after progression., Materials Ad Methods: In this non interventional, retrospective study, patients treated with olaparib in 13 centers, according to the label, have been collected and analyzed. Primary objectives of the study are to describe effectiveness and safety of olaparib in a real world setting with a focus on post progression treatments and response., Results: 234 patients were analyzed. All patients were BRCA mutated and most of them had germline mutations. Around 50% of the patients received olaparib after 3 or more lines of platinum based chemotherapy achieving a radiologic complete (CR) or partial response. 12.4% patients with stable disease were also included. Median PFS was 14.7 months (95% CI:12.6-18), with statistically longer PFS in patients with normal serum Ca125 at baseline, a CR after last platinum based therapy and that received olaparib after second platinum based therapy. Median OS was not reached. Most frequent G3-G4 toxicity was anaemia (6%) with dose discontinuation and dose reduction in 11 (4.7%) and 49 (20.9%) of cases, respectively. Among 66 patients receiving further treatment after olaparib progression and evaluable for response, ORR was 22.2, 11.1% and 9.5% in patients with Platinum Free interval (PFI) of more than 12 months, between 6 and 12 months and less than 6 months, respectively., Conclusions: Olaparib is effective and safe in real world setting. Data on post-progression treatments seem to suggest cross resistance with chemotherapy and need to be confirmed in larger studies because of the potential importance in clinical practice decisions., (Copyright © 2019. Published by Elsevier Inc.)

Background: In real-world practice, eribulin mesylate provides significant survival benefit, with a manageable safety profile in heavily pretreated patients with metastatic breast cancer (MBC)., Methods: In this prospective, open-label, multicentre, observational study we evaluated the effectiveness and tolerability of eribulin as third-line treatment in a homogeneous population. The primary endpoints were the safety profile and response in metastatic sites; secondary endpoints included the response in different subtypes, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS)., Results: From 2013 to 2016, 118 women were treated in 21 Sicilian institutions; the median age was 58 years (range 29-79), with 69% of patients under 65. The median cycles of eribulin were 5.5 (range 1-26). The most common adverse event was neutropenia (9.3%, 3 cases of grade 3, 4 of grade 4); only 1 case of QT prolongation was reported. Eribulin was effective in controlling metastatic disease in all sites, and it achieved the highest ORR in brain (16%) and liver (14.9%). Median OS was 31.8 months (95% CI 27.9-34.4) and median PFS 5.5 months (95% CI 4.2-6.6). PFS was 5.2 months (95% CI 2.8-8.4) in patients with triple-negative subtype. Median PFS was longer in patients over 65 years (6.1 months, 95% CI 4.4-8.3). In patients who had visceral metastases PFS was 5.5 months (95% CI 95% 3.5-6.6) and OS 33.9 months (95% CI 29.8-40.8)., Conclusions: Eribulin as third-line treatment shows an acceptable safety profile and a substantial antitumour activity in the treatment of MBC, even in elderly patients and in those with visceral disease., Competing Interests: Conflict of interest statement: The author(s) declare that there are no conflicts of interest., (© The Author(s), 2019.)

Epithelial ovarian cancer is the most lethal gynecologic malignancy. In most women, it is diagnosed at an advanced stage, which largely explains the poor prognosis of this malignancy. Germline mutations of the genes BRCA1 and BRCA2, which encode proteins essential for the repair of double-strand DNA breaks through homologous recombination, lead to increased cancer predisposition. BRCA mutations are present in approximately 14% of epithelial ovarian cancers. Somatic BRCA mutations have also been described. Current first-line treatment of high-grade epithelial ovarian cancer includes debulking surgery followed by combination chemotherapy, usually carboplatin and paclitaxel. Ovarian cancer is highly sensitive to chemotherapy, in particular to platinum drugs. Most patient will achieve remission with initial chemotherapy, but most will eventually experience disease recurrence. Targeted therapies, including the anti-angiogenic agent bevacizumab and oral poly (ADP-ribose) polymerase (PARP) inhibitors, have been recently approved for the treatment of ovarian cancer, based on the results from randomized clinical trials showing significant benefits in terms of progression-free survival, with acceptable tolerability and no detrimental effects on quality of life. Olaparib, the first PARP inhibitor to be granted approval, is currently indicated as maintenance monotherapy in ovarian cancer patients with relapsed disease and mutated BRCA who have achieved a complete or partial response to platinum-based chemotherapy. The analysis of BRCA mutational status has, therefore, also become crucial for therapeutic decisions. Such advances are making personalized treatment of ovarian cancer feasible. Here we briefly review treatments for platinum-sensitive, high-grade serous epithelial ovarian cancer that are currently available in Italy, with a focus on targeted therapies and the relevance of BRCA mutational analysis. Based on the evidence and on current guidelines, we propose strategies for the tailored treatment of patients with relapsed ovarian cancer that take into account BRCA mutational status and the treatment received in the first-line setting.

Background: We reported the results of an Italian large retrospective analysis that evaluated the effectiveness and safety of T-DM1 in 'field-practice' breast cancer patients. We performed a sub-analysis to investigate the clinical activity of T-DM1 in patients with brain metastases (BMs)., Methods: The records of 87 adult women with HER2-positive breast cancer and BMs treated with T-DM1 were reviewed. Their clinical outcomes were compared with those of 216 patients without central nervous system (CNS) involvement., Results: Response to T-DM1 treatment in BMs was available for 53 patients in the BM group (60.9%): two patients reported a complete response (3.8%), 11 patients obtained partial response (20.7%; overall response rate: 24.5%), 16 patients had a stable disease (30.1%). Regarding extracranial disease, a total of 77 and 191 patients were evaluable for response in BM group and non-BM group, respectively. The overall response rate was 35.1% in the BM group and 38.3% in the non-BM group; disease control rate was 53.3% and 66.6%, respectively. At a median follow-up of 16 months (range: 1-55), median cumulative progression-free survival (PFS) was 7 months (95% CI: 5.4-8.6) in the BM group and 8 months (95% CI: 5.7-10.3) in the non-BM group. In the second-line setting, PFS was 5 (95% CI: 3.1-6.9) versus 11 (95% CI: 7.1-14.9) months (p = 0.01). Overall survival was 14 months (95% CI: 12.2-15.8) in the BM group and 32 months (95% CI: 24.4-39.6) in the non-BM group (p < 0.0001)., Conclusions: T-DM1 is active in breast cancer patients with BMs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Following pre-migration screening for tuberculosis (TB), migrants who are deemed to be at a high risk of developing TB must attend post-entry follow-up in Australia. We aimed to evaluate the effectiveness of post-migration TB follow-up in the state of New South Wales to diagnose TB in these high-risk migrants. In this retrospective cohort study, we assessed the risk of TB in migrants who arrived in New South Wales between 2000 and 2015 and were referred for post-migration follow-up. Clinical notes were examined for a nested cohort to determine whether TB was diagnosed via the follow-up programme or via passive case finding. Of the 32 550 migrants referred for follow-up, 428 (1.3%) developed TB. The incidence of TB was 436 per 100 000 person-years (95% CI 384-491 per 100 000 person-years) in the first 2 years after arrival and 128 per 100 000 person-years (95% CI 116-140 per 100 000 person-years) over the mean study observation period of 10.3 years. An estimated 63% of cases were diagnosed via follow-up. TB notifications occurred 0.55 years earlier since time of arrival in Australia in migrants who attended follow-up than in those who did not. Post-migration follow-up detected 63% of TB cases in high-risk migrants and potentially prevented delay of TB diagnosis., Competing Interests: Conflict of interest: None declared.

Electrochemical dissolution of metallic copper into slightly acidic aqueous solutions of chitosan yields a clear and stable dispersion of Copper Oxide nanoparticles into the organic polymer host. The electrochemically synthesized chitosan:CuOx nanocomposite is characterized by means of spectrophotometry, frequency domain electrical measurements and morphological analysis. Solid state electrochemical cells having pure chitosan as the electrolyte and using chitosan:CuOx as the electrode, are developed and characterized by means of electrical measurements performed in the ±1 V voltage window. The current-voltage loops of the cells, measured in deionized water, are found to reversibly change in response to hydrogen peroxide added to the water in 0.2 μM subsequent steps. Such changes, clearly distinguishable from changes recorded in response to other analytes, can be exploited in order to develop a hydrogen peroxide sensor able to work without the need for any supporting electrolyte., Competing Interests: The authors declare no conflict of interests.

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (mBC). The aim of this 'field-practice' study was to investigate the efficacy and safety of T-DM1, focusing on treatment line, previous lapatinib treatment and patterns of metastasis. Three hundred and three patients with HER2-positive mBC who received T-DM1 were identified by reviewing the medical records of 24 Italian Institutions. One hundred fourty-nine (49%) and 264 (87%) had received prior hormonal treatment and/or anti-HER2 targeted therapy, respectively. Particularly, 149 patients had been previously treated with lapatinib. The objective response rate (ORR) was 36.2%, and 44.5% when T-DM1 was administrated as second-line therapy. Considering only patients with liver metastases, the ORR was 44.4%. The median progression-free survival (PFS) was 7.0 months in the overall population, but it reached 9.0 and 12.0 months when TDM-1 was administered as second- and third-line treatment, respectively. In conclusion, in this 'real-word' study evaluating the effects of T-DM1 in patients with HER2-positive mBC who progressed on prior anti-HER2 therapies, we observed a clinically-relevant benefit in those who had received T-DM1 in early metastatic treatment-line and in subjects previously treated with lapatinib., Competing Interests: CONFLICTS OF INTEREST The authors have declared no conflicts of interest.

Epidermal growth factor receptor (EGFR) plays a significant role in non-small cell lung cancer (NSCLC), the most prevalent form of lung cancer worldwide. Therefore, EGFR may be a useful molecular target for personalized therapy utilizing tyrosine kinase inhibitors (TKIs). Somatic activating EGFR mutations may be used to identify tumors sensitive to the effects of small-molecule EGFR-TKIs (gefitinib and erlotinib), and alternative, less frequently observed mutations, including the majority of mutations identified within exon 20, may be associated with a lack of response to TKIs. However, due to the comparative rarity of EGFR exon 20 mutations, clinical information concerning the association between EGFR exon 20 mutations and responsiveness to TKIs has been limited within the relevant literature, particularly for certain rare mutations, including p.S768I. The current study reports the case of a patient with NSCLC harboring a p.S768I mutation in the EGFR gene [a substitution at codon 768 of exon 20 (c.2303G>T, p.S768I)], as well as a mutation at codon 719, exon 18 (p.G719A). The relevant literature concerning this rare EGFR somatic mutation is also reviewed.

Objective: To evaluate the efficacy and tolerability of a neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy in patients with locally advanced cervical carcinoma., Methods: Patients with histologically confirmed locally advanced cervical carcinoma, aged ≥18 years, were treated with intravenous ifosfamide 5,000 mg/m² and mesna 5,000 mg/m², on day 1; intravenous paclitaxel 175 mg/m² and cisplatin 75 mg/m², on day 2; every 3 weeks for three cycles. Following chemotherapy, operable patients underwent radical hysterectomy and pelvic lymphadenectomy, and, if necessary, adjuvant radiotherapy., Results: One hundred fifty-two patients with median age 53 years (range, 24 to 79 years), FIGO stage IIB in 126 (89%), were treated with chemotherapy for median 3 cycles (range, 1 to 3). Treatment was delayed or withdrawn in 23 patients (15%). One hundred thirty-nine patients (91%) underwent surgery. Postchemotherapy pathological complete response rate was 18% (25 patients). Postoperative radiotherapy was administered in 100 patients (72%). The 5-year overall survival and progression-free survival were 87.3% (95% confidence interval [CI], 84.5 to 90.3) and 76.4% (95% CI, 73.5 to 79.5), respectively., Conclusion: Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy was feasible and effective in the treatment of locally advanced cervical carcinoma patients with older age and more advanced disease stage than reported in previous studies. Hematological and renal toxicity could be carefully prevented.

Aim: This multicenter study describes the effectiveness of eribulin in current practice., Patients & Methods: In total, 78 patients with advanced metastatic breast cancer, previously treated with two or more chemotherapy lines were enrolled., Results: The median duration of response and disease stability were 7.5 (5.4-9.5) and 8.9 (6.2-11.6) months, respectively, with a clinical benefit (CB) at 6 months in 41% of patients. CB in visceral and nonvisceral metastases were 72.7 and 88.9%, respectively. Eribulin was active also in brain metastases, with 47% CB. The activity was shown in all biological subtypes. Toxicities were manageable., Conclusion: Our study confirms the effectiveness of eribulin mesylate in the treatment of patients with metastatic breast cancer and two or more lines of chemotherapy, in particular in the good disease control at the different metastatic sites.

Aims and Background: The addition of trastuzumab to chemotherapy for HER2-positive metastatic breast cancer has significantly improved progression-free survival and overall survival, although most patients develop resistance or have a primarily resistant disease. The aim of the study was to describe the efficacy and safety of a first-line treatment in unselected metastatic HER2-positive breast cancer patients, treated according to clinical practice., Methods: From 2000 to 2009, we conducted a retrospective multi-institutional analysis of 182 consecutive patients with HER2-positive metastatic breast cancer who underwent first-line treatment with trastuzumab. The primary end points were progression-free survival and overall survival; the secondary end points were survival after progression in patients treated with second-line chemotherapy with or without trastuzumab and safety. A total of 172 patients were analyzed., Results: Median progression-free survival and overall survival were 1.2 (95% CI, 1.1-1.4) and 4.4 years (95% CI, 3.6-5.4), respectively. For 100 patients who received second-line chemotherapy, median survival after progression was significantly longer in those who also received trastuzumab: 2.8 (95% CI, 2.1-4.0) versus 1.2 years (95% CI, 0.6-1.9)., Conclusions: Although based on retrospective data, the study confirms the role of trastuzumab as first-line treatment in metastatic breast cancer outside of a controlled trial. Moreover, information obtained on the use of trastuzumab beyond disease progression supports its use in this setting.

A conducting composite prepared by dispersing multi-walled carbon nanotubes (MWCNTs) into a host matrix consisting of Nafion, electrochemically doped with copper, has been prepared, characterized and used to modify one of the gold electrodes of simply designed electrochemical cells having copier grade transparency sheets as substrates. Electrical measurements performed in deionized water show that the Au/Nafion/Au-MWCNTs-Nafion:Cu cells can be successfully used in order to detect the presence of p-aminophenol (PAP) in water, without the need for any supporting electrolyte. The intensity of the redox peaks arising when PAP is added to deionized water is found to be linearly related to the analyte in the range from 0.2 to 1.6 µM, with a detection limit of 90 nM and a sensitivity of 7 µA·(µM(-1))·cm(-2).

In this paper an approach for designing a programmable, very low noise, high accuracy voltage source for biasing devices under test in low frequency noise measurements is proposed. The core of the system is a supercapacitor based two pole low pass filter used for filtering out the noise produced by a standard DA converter down to 100 mHz with an attenuation in excess of 40 dB. The high leakage current of the supercapacitors, however, introduces large DC errors that need to be compensated in order to obtain high accuracy as well as very low output noise. To this end, a proper circuit topology has been developed that allows to considerably reduce the effect of the supercapacitor leakage current on the DC response of the system while maintaining a very low level of output noise. With a proper design an output noise as low as the equivalent input voltage noise of the OP27 operational amplifier, used as the output buffer of the system, can be obtained with DC accuracies better that 0.05% up to the maximum output of 8 V. The expected performances of the proposed voltage source have been confirmed both by means of SPICE simulations and by means of measurements on actual prototypes. Turn on and stabilization times for the system are of the order of a few hundred seconds. These times are fully compatible with noise measurements down to 100 mHz, since measurement times of the order of several tens of minutes are required in any case in order to reduce the statistical error in the measured spectra down to an acceptable level.

Electrical noise sources are basic building blocks in many measurement and instrumentation applications and in communication systems. In this paper, we propose a quite simple topology for the realization of a programmable, wide bandwidth, white noise current source that requires only two resistors and one operational amplifier. We validate the proposed approach by means of SPICE simulations and demonstrate, by means of proper measurements, the capability of generating a flat current noise spectrum in a frequency range up to four decades from a few Hz up to 100 kHz.

Electrochemical devices using as substrates copier grade transparency sheets are developed by using ion conducting Nafion:polypyrrole mixtures, deposited between gold bottom electrodes and upper electrodes based on Multi Walled Carbon Nanotubes (MWCNTs). The electrical properties of the Nafion:polypyrrole blends and of the gold/Nafion:polypyrrole/MWCNTs devices are investigated under dry conditions and in deionized water by means of frequency dependent impedance measurements and time domain electrical characterization. According to current-voltage measurements carried out in deionized water, the steady state current forms cycles characterized by redox peaks, the intensity and position of which reversibly change in response to H2O2, with a lower detection limit in the micromolar range. The sensitivity that is obtained is comparable with that of other electrochemical sensors that however, unlike our devices, require supporting electrolytes.

Aims: This report describes a positive experience of adverse event (AE) management of a multidisciplinary clinical team and 18 patients with late-stage renal cell carcinoma and hepatocellular carcinoma attending the Day Hospital Unit of the 'Centro Catanese di Oncologia Humanitas' (Italy) over a 2-year period., Methods: The management strategy was based on preventive measures for reducing the development of cutaneous AEs, including pain, risk of infection and patient discomfort, while avoiding the discontinuation or the reduction of the sorafenib dosage., Results: As of July 2011, eight patients were still under treatment with sorafenib; seven patients experienced cutaneous AEs and two reported severe cutaneous AEs., Conclusion: Our treatment approach seemed to reduce the incidence and/or severity of AEs, keeping patients in treatment, which is essential for good treatment outcomes.

Low frequency noise measurements are among the most sensitive tools for the investigation of the quality and of the reliability of semiconductor devices. The sensitivity that can be obtained depends on the background noise of the low noise preamplifier coupled to the device under test (DUT) that, at very low frequencies, is dominated by flicker noise. The low frequency noise produced by the DUT, on the other end, is very often the most interesting signal to be detected and analyzed. In this work we propose a very simple topology for the realization of a general purpose low noise preamplifier whose noise performances, at very low frequencies (below 10 Hz), are significantly better than those that can be obtained by the most popular commercial instrumentation. Indeed, a gain of 80 dB with a pass band extending from a few tens of mHz up to a few kHz with an equivalent input voltage noise as low as 14 nV/square root(Hz) (100 mHz), 1.4 nV/square root(Hz) (1 Hz), 1.0 nV/square root(Hz) (10 Hz), and 0.8 nV/square root(Hz) (1 kHz) are consistently obtained by using quite standard electronic components and with no need for trimming and/or calibration steps. Moreover, the junction field-effect transistor input stage of the amplifier is characterized by an equivalent input current noise below 4 fA/square root(Hz) in the entire bandwidth, resulting in negligible background noise degradation for DUT impedances in excess of 100 kohms.

Johne's disease is a chronic granulomatous enteritis in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). The disease is responsible for considerable economic losses in the livestock industry and in particular within the dairy sector. A more effective vaccine against Johne's disease would be of major benefit. In this study, we developed an efficient procedure for identifying mutants of MAP with reduced virulence that are potential live vaccine candidates against Johne's disease. A mariner transposon was used to create random insertional libraries in two different MAP strains (989 and k10), an effective cattle macrophage survival system was developed, and a total of 1890 insertion mutants were screened by using a 96-prong multi-blot replicator (frogger) system. Two of the transposon mutants with poor survival ability in macrophages were tested in mice. These strains were found to be attenuated in vivo, thereby validating the further use of this macrophage screening system to identify MAP mutants with potential as candidate vaccines against Johne's disease.

The genome of Mycobacterium tuberculosis encodes many proteins involved in fatty acid metabolism, a subset of which are required for virulence. The Mycobacterium tuberculosis fadB4 gene, which shares strong similarity with oxidoreductases and fatty acid synthases, is up-regulated during infection of macrophages and is predicted to protect the bacterium from the hostile environment of the host cell. In order to determine if fadB4 plays a role in the virulence of M. tuberculosis, we constructed a M. tuberculosis mutant in which the fadB4 had been disrupted (DeltafadB4). Surprisingly, DeltafadB4, grew more rapidly in host cells compared to wild-type M. tuberculosis or the DeltafadB4 or the gene-disrupted strain complemented with fadB4. In addition, macrophages infected with DeltafadB4 displayed reduced secretion of the cytokine TNF-alpha, suggesting a role for the FadB4 protein in influencing the pro-inflammatory host response to M. tuberculosis. After infection of mice, DeltafadB4 demonstrated an increased replication at early time-points post-infection compared to the growth of wild-type M. tuberculosis. This increased capacity of DeltafadB4 to replicate in vivo was reflected in the decreased time to death of immuno-deficient RAG-1(-/-) mice infected with M. tuberculosis lacking the fadB4 gene. Therefore fadB4 is part of the family of genes whose expression serves to regulate the virulence of M. tuberculosis within the host.

The properties of a differential transconductance amplifier coupled with a four channel measurement system are exploited in order to reach a very high sensitivity in current noise measurements. In particular, it is demonstrated that, in proper conditions, the noise contributions coming from the active and passive devices that make up the transresistance amplifier can be virtually eliminated. Moreover, the proposed measurement method allows the evaluation of the impedance of the device under test from noise measurement data. Actual measurement results are also reported that demonstrate the effectiveness of the proposed approach.

The control of mycobacterial infections is dependent on the finely tuned synergism between the innate and adaptive immune responses. The macrophage is the major host cell for Mycobacterium tuberculosis and the degree of virulence of mycobacteria may influence the initial macrophage response to infection. The cell wall molecule, phthiocerol dimycocerosate (DIM), is an important virulence factor that influences the early growth of M. tuberculosis in the lungs. To explore the basis for this effect we have compared the early gene response of human THP-1 macrophages to infection with virulent M. tuberculosis and the DIM-deficient DeltafadD26 M. tuberculosis strain using microarrays. Detailed analysis revealed a common core of macrophage genes, which were rapidly induced following infection with both strains, and deficiency of DIM had no significant effect on this initial macrophage transcriptional responses. In addition to chemokines and pro-inflammatory cytokines, the early response genes included components of the Toll-like receptor signalling, antigen presentation and apoptotic pathways, interferon response genes, cell surface receptors and their ligands, including TNF-related apoptosis inducing ligand (TRAIL) and CD40, and other novel genes. Therefore, although fadD26 deficiency is responsible for the early attenuation of the growth of M. tuberculosis in vivo, this effect is not associated with differences in the initial macrophage transcriptional response.

In diagnostic examinations performed in nuclear medicine, radio-isotopes with a relatively short half-life are used, the quantity varying according to the type of examination. After administration of the labelled substance, the patient becomes a large source of ionizing radiations. During the course of a scintigraphic examination, the operator is obliged to go near the couch to assist the patient in the positions and will therefore inevitably be in this radiation field. The paper reports the radio-activity levels recorded at gonad and eye levels of the operator in positions most frequently held during the course of the most commonly performed scintigraphic examinations using a G.E. STARCAM 500 A gamma-camera.

The paper presents the results of an analysis made on the electromagnetic field levels around RF and MW equipment used for medical purposes to achieve induced thermogenesis in body areas affected by disease. An irradiation diagram was constructed for some of the most widely used devices in clinical practice and measurements were made on RF devices to identify the influence of obstacles in determining electric field levels, such as accessories or persons present in the working environment. Electric field and power density levels were checked, as can be measured at a distance of 100 cm at identical selected power during a typical "lumbar-dorsal spine" treatment using different types of RF and MW devices, to identify the different degree of electromagnetic pollution that each of the devices causes.

Hemangiopericytoma is a rare type of neoplasia originating from the Zimmermann pericytes and can arise in numerous sites. As it is difficult to correlate the histologic aspect with the prognosis, it was considered advisable to take account of other factors such as age and tumoral site. Aggressive surgery followed by irradiation therapy is suggested as the most suitable management. Hyperthermia also was adopted in treating subcutaneous metastasis, but its role has yet to be fully defined.