A high-resolution neutron spectroscopic camera for the SPARC tokamak based on the Jet European Torus deuterium-tritium experience.

Dedicated nuclear diagnostics have been designed, developed, and built within EUROFUSION enhancement programs in the last ten years for installation at the Joint European Torus and capable of operation in high power Deuterium-Tritium (DT) plasmas. The recent DT Experiment campaign, called DTE2, has been successfully carried out in the second half of 2021 and provides a unique opportunity to evaluate the performance of the new nuclear diagnostics and for an understanding of their behavior in the record high 14 MeV neutron yields (up to 4.7 × 1018 n/s) and total number of neutrons (up to 2 × 1019 n) achieved on a tokamak. In this work, we will focus on the 14 MeV high resolution neutron spectrometers based on artificial diamonds which, for the first time, have extensively been used to measure 14 MeV DT neutron spectra with unprecedented energy resolution (Full Width at Half Maximum of ≈1% at 14 MeV). The work will describe their long-term stability and operation over the DTE2 campaign as well as their performance as neutron spectrometers in terms of achieved energy resolution and high rate capability. This important experience will be used to outline the concept of a spectroscopic neutron camera for the SPARC tokamak. The proposed neutron camera will be the first one to feature the dual capability to measure (i) the 2.5 and 14 MeV neutron emissivity profile via the conventional neutron detectors based on liquid or plastics scintillators and (ii) the 14 MeV neutron spectral emission via the use of high-resolution diamond-based spectrometers. The new opportunities opened by the spectroscopic neutron camera to measure plasma parameters will be discussed.

Expression of type I interferon-associated genes at antiretroviral therapy interruption predicts HIV virological rebound.

Although certain individuals with HIV infection can stop antiretroviral therapy (ART) without viral load rebound, the mechanisms under-pinning 'post-treatment control' remain unclear. Using RNA-Seq we explored CD4 T cell gene expression to identify evidence of a mechanism that might underpin virological rebound and lead to discovery of associated biomarkers. Fourteen female participants who received 12 months of ART starting from primary HIV infection were sampled at the time of stopping therapy. Two analysis methods (Differential Gene Expression with Gene Set Enrichment Analysis, and Weighted Gene Co-expression Network Analysis) were employed to interrogate CD4+ T cell gene expression data and study pathways enriched in post-treatment controllers versus early rebounders. Using independent analysis tools, expression of genes associated with type I interferon responses were associated with a delayed time to viral rebound following treatment interruption (TI). Expression of four genes identified by Cox-Lasso (ISG15, XAF1, TRIM25 and USP18) was converted to a Risk Score, which associated with rebound (p < 0.01). These data link transcriptomic signatures associated with innate immunity with control following stopping ART. The results from this small sample need to be confirmed in larger trials, but could help define strategies for new therapies and identify new biomarkers for remission.

Investigation on the role of consumer health orientation in the use of food labels.

OBJECTIVE: This study explored the relationship between health orientation (i.e. individual motivation to engage in healthy attitudes, beliefs and behaviours) and consumers' use of nutritional information on food labels. Specifically, this study analysed the relationship between a number of direct investments in health (namely those behaviours that can contribute directly to maintain a good health status) and use of nutritional information on food labels. STUDY DESIGN: Data for the analysis were collected through face-to-face interviews with a sample of 540 Italian consumers in charge of their grocery shopping. Forty grocery stores, including supermarkets and hypermarkets, were selected using a systematic sampling technique. METHODS: Data were analysed using three equations and accounting for endogeneity issues. RESULTS: This study found that those consumer groups with low health orientation (specifically smokers, those who do not exercise regularly, and those with an unhealthy body weight) show little interest in nutritional labels. CONCLUSION: Nutritional labels as a tool to promote healthier food choices have a limited effect on those consumers in greatest need of pursuing healthier lifestyle habits. Alternative policy intervention should be undertaken to reach these consumer groups.

An improved method for detecting telomere size differences in T-lymphocyte interphases from older people with Down syndrome with and without mild cognitive impairment.

Telomere size (quantified by fluorescence intensity and physical lengths) in short-term T-lymphocyte cultures from adults with Down syndrome (DS) with and without mild cognitive impairment (MCI-DS) or dementia was compared. For these studies, dementia status was determined based on longitudinal assessments employing a battery of cognitive and functional assessments developed to distinguish adult-onset impairment from preexisting developmental disability. In the course of our studies using a MetaSystems Image Analyzer in combination with ISIS software and a Zeiss Axioskop 2, we found that Fluorescein isothiocyanate (FITC) telomere fluorescence referenced to chromosome 2-identified FITC probe fluorescence as a nontelomere standard (telomere/cen2 ratio) showed great promise as a biomarker of early decline associated with Alzheimer's disease (AD) in this high-risk population. We have now obtained a cen (2) CY3 probe that can clearly be distinguished from the blue-green FITC interphase telomere probe, providing a clear distinction between telomere and centromere fluorescence in both interphase and metaphase. We used FITC/CY3 light intensity ratios to compare telomere length in interphases in adults with DS with and without MCI-DS or dementia. Five age-matched female and five age-matched male pairs (n = 10) all showed clear evidence of telomere shortening associated with clinical progression of AD (P < 0.002 - P < 0.000001), with distributions of mean values for cases and controls showing no overlap. We also examined the time needed for microscopy using interphase versus metaphase fluorescence preparations. With interphase preparations, examination time was reduced by an order of magnitude compared with metaphase preparations, indicating that the methods employed herein have considerable practical promise for translation into broad diagnostic practice.

Determining exhaust fumes exposure in chainsaw operations.

The objective of this study was to investigate the inhalation exposure of forest operators to polycyclic aromatic hydrocarbons (PAHs) and BTEX (benzene, toluene, ethylbenzene and total xylenes) contained in the exhaust fumes released from chainsaws and to suggest possible countermeasures. The study was carried out in four silvicultural treatments (coppice clearcut, conifer thinning, conifer pruning, and sanitary cut), using three types of chainsaw fuel (normal two-stroke petrol mix and two alkylate fuels). Eighty personal air samples were collected; IOM samplers combined with Amberlite XAD-2 sorbent tubes were used for collecting PAHs and Radiello® samplers were used for BTEX. Results indicate that none of the four silvicultural treatments significantly affected the PAHs and BTEX inhalation exposure of forest workers. On the other hand, statistically significant differences were recorded in the inhalation exposure to PAHs and BTEX when using different fuel types. In particular, the inhalation exposure to PAHs and BTEX was generally one order of magnitude lower when using modern alkylate fuels as compared to the traditional oil and lead-free petrol mixture. The small, non-statistically significant differences in inhalation exposure recorded between the two alkylate fuels suggests that the two fuels might be equivalent in terms of quality. Our study indicates that while forest workers are exposed to PAHs and BTEX, the maximum values are generally well below accepted occupational exposure limits.

Tumor necrosis factor-α impairs oligodendroglial differentiation through a mitochondria-dependent process.

Mitochondrial defects, affecting parameters such as mitochondrial number and shape, levels of respiratory chain complex components and markers of oxidative stress, have been associated with the appearance and progression of multiple sclerosis. Nevertheless, mitochondrial physiology has never been monitored during oligodendrocyte progenitor cell (OPC) differentiation, especially in OPCs challenged with proinflammatory cytokines. Here, we show that tumor necrosis factor alpha (TNF-α) inhibits OPC differentiation, accompanied by altered mitochondrial calcium uptake, mitochondrial membrane potential, and respiratory complex I activity as well as increased reactive oxygen species production. Treatment with a mitochondrial uncoupler (FCCP) to mimic mitochondrial impairment also causes cells to accumulate at the progenitor stage. Interestingly, AMP-activated protein kinase (AMPK) levels increase during TNF-α exposure and inhibit OPC differentiation. Overall, our data indicate that TNF-α induces metabolic changes, driven by mitochondrial impairment and AMPK activation, leading to the inhibition of OPC differentiation.

A novel approach combining the Calgary Biofilm Device and Phenotype MicroArray for the characterization of the chemical sensitivity of bacterial biofilms.

A rapid method for screening the metabolic susceptibility of biofilms to toxic compounds was developed by combining the Calgary Biofilm Device (MBEC device) and Phenotype MicroArray (PM) technology. The method was developed using Pseudomonas alcaliphila 34, a Cr(VI)-hyper-resistant bacterium, as the test organism. P. alcaliphila produced a robust biofilm after incubation for 16 h, reaching the maximum value after incubation for 24 h (9.4 × 10(6) ± 3.3 × 10(6) CFU peg(-1)). In order to detect the metabolic activity of cells in the biofilm, dye E (5×) and menadione sodium bisulphate (100 µM) were selected for redox detection chemistry, because they produced a high colorimetric yield in response to bacterial metabolism (340.4 ± 6.9 Omnilog Arbitrary Units). This combined approach, which avoids the limitations of traditional plate counts, was validated by testing the susceptibility of P. alcaliphila biofilm to 22 toxic compounds. For each compound the concentration level that significantly lowered the metabolic activity of the biofilm was identified. Chemical sensitivity analysis of the planktonic culture was also performed, allowing comparison of the metabolic susceptibility patterns of biofilm and planktonic cultures.

Low abdominal contribution to breathing as daytime predictor of nocturnal desaturation in adolescents and young adults with Duchenne Muscular Dystrophy.

In the respiratory management of DMD patients it is still under debate what parameter should indicate the correct timing for institution of nocturnal non-invasive ventilation (NIV), in addition to forced vital capacity, which is generally considered as a prognostic marker of disease progression. The aim of this study was to determine if volume variations of rib cage and abdominal compartments measured by Opto-Electronic Plethysmography can be helpful to distinguish between those patients who are in the early stages of nocturnal oxygen desaturation development and those who do not yet. Pulmonary function, abdominal contribution to tidal volume and to inspiratory capacity (%Abd IC) and a set of breathing pattern indexes were assessed in 40 DMD patients older than 14 years and not yet under nocturnal NIV. ROC analysis revealed that among all the considered parameters, %Abd IC in supine position was the best discriminator between DeSat (at least 10% of the night time with SpO(2) < 95%) and NonDeSat patients, providing an area under the curve with 95%CI equal to 0.752. In conclusion, in adolescents and adults DMD patients who present either no sign or only mild nocturnal oxygen desaturation, a reduced abdominal contribution to inspiratory capacity is a marker of the onset of diaphragm weakness and should be considered to identify the correct timing for the institution of nocturnal NIV.

Respiratory pattern in an adult population of dystrophic patients.

We studied respiratory function and Chest Wall kinematics in a large population of adult patients affected by slow course muscular dystrophies such as Limb-Girdle Muscular Dystrophy (LGMD, n=38), Becker Muscular Dystrophy (BMD, n=20) and Facio-Scapulo Humeral Dystrophy (FSHD, n=30), through standard spirometry and through the Optoelectronic Plethysmography, to measure the thoraco-abdominal motion during Quiet Breathing and Slow Vital Capacity maneuvers. Within the restrictive pulmonary syndrome characterizing LGMD and FSHD, several different thoraco-abdominal patterns compared to those of healthy subjects were present in the more advanced stages of the disease. These differences were present in the seated position, during the execution of a maximal maneuver such as Slow Vital Capacity. A global respiratory (both inspiratory and expiratory) muscle involvement was more pronounced in the LGMD and FSHD than in the BMD patients, and a significant reduction of abdominal contribution in wheelchair bound patients was observed. In conclusion, OEP technique is able to reveal mild initial modifications in the respiratory muscles in FSHD and LGMD patients, which could be helpful for functional and new therapeutic strategy evaluation.

Pralatrexate - from bench to bedside.

Pralatrexate (PDX, 10-propargyl 10-deazaaminopterin) is an exciting new chemotherapeutic agent with promising activity in T-cell lymphomas and non-small cell lung cancer. It has been granted approval by the Food and Drug administration (FDA) for use in the treatment of relapsed and refractory peripheral T-cell lymphomas (PTCL). Pralatrexate belongs to a class of antineoplastic agents known as antifolates that also include methotrexate, pemetrexed and ralitrexed. Pralatrexate was rationally designed to have high affinity for the one carbon-reduced folate carrier (RFC-1) which leads to better cellular internalization of the drug and a greater antitumor effect than methotrexate. The following monograph is a story of the development of this drug in a systematic fashion from the bench to the bedside.

Acute inflammatory response secondary to intrapleural administration of two types of talc.

Intrapleural instillation of talc has been used in the treatment of recurrent pleural effusions but can, in rare instances, result in respiratory failure. Side-effects seem to be related to composition, size and inflammatory power of talc particles. The aim of this study was to evaluate the inflammatory response to intrapleural injection of talc containing small particles (ST) or talc containing particles of mixed size (MT). 100 rabbits received intrapleural talc, 50 with ST (median 6.41 mum) and 50 with MT (median 21.15 mum); the control group was composed of 35 rabbits. Cells, lactate dehydrogenase, C-reactive protein (CRP), interleukin (IL)-8 and vascular endothelial growth factor were evaluated in serum and bronchoalveolar lavage at 6, 24, 48, 72 and 96 h. Lung histology and the presence of talc were also analysed. Statistics were performed using ANOVA and an unpaired t-test. Most of the parameters showed greater levels in the animals injected with talc than in the controls, suggesting a systemic and pulmonary response. Higher serum levels of CRP and IL-8 were observed in the animals injected with ST. Talc particles were observed in both lungs with no differences between groups. Lung cell infiltrate was more evident in the ST group. In conclusion, talc with larger particles should be the preferred choice in clinical practice in order to induce safer pleurodesis.

Abdominal volume contribution to tidal volume as an early indicator of respiratory impairment in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is characterised by progressive loss of muscular strength that leads to an increasingly restrictive pulmonary syndrome. However, it is still not clear whether this determines alterations in the breathing pattern. We studied: 66 DMD patients at different stages of the disease (mean+/- sem age 12.6+/-0.6 yrs, range 5-22 yrs of age), subdivided into four groups according to age; and 21 age-matched healthy male controls. Spirometry, lung volumes and nocturnal oxygen saturation were measured in all DMD patients. Ventilatory pattern and chest wall volume variations were assessed by optoelectronic plethysmography during spontaneous breathing both in seated and supine positions. Whilst in a seated position, no significant differences were found between patients and controls or between different age groups. In the supine position, the average contribution of abdominal volume change (DeltaV(AB)) to tidal volume progressively decreased with age (p<0.001). The patients who showed nocturnal hypoxaemia showed significantly lower Delta V(AB). In conclusion, chest wall motion during spontaneous breathing in awake conditions and in supine position is an important indicator of the degree of respiratory muscle impairment in DMD. DeltaV(AB) is not only an important marker of the progression of the disease but is also an early indicator of nocturnal hypoxaemia.

Yeast as a model to investigate the mitochondrial role in adaptation to dietary fat and calorie surplus.

Several research strategies are focused towards understanding the genetic basis and molecular mechanisms that regulate uptake, synthesis, deposition, and mobilization of lipids, in the context of energy homeostasis. Because of the complexity of the problem, major input comes from the use of model systems. The aim of this work was to test the feasibility of using yeast as a model organism for studies related to dietary challenges due to high fat diet and investigate the correlation between FA metabolism and oxidative metabolism. In particular, we ask to what extent the utilization of oleic acid is dependent on mitochondrial function. We studied growth on oleic acid as a sole carbon source, and oleate stress (growth in 2 and 5% oleate) in both laboratory (BY4741 wild-type and Deltasco1, Deltasco2, Deltatgl3, Deltatgl4 mutants) and natural strains, comparing the growth phenotypes with the respiratory behaviour for each strain. We confirmed that respiratory competence is fundamental for growth on oleic acid, since the respiratory deficient mutant Deltasco1 was unable to grow on oleic acid. In order to understand if the ability to use oleate as carbon source and adapt to high oleate concentrations is a general trait for the Saccharomyces cerevisiae genus, we also studied some natural strains, both diploid and haploid, identifying two meiotic derivatives of SGU90 as unable to grow in oleic acid as a sole carbon source. We investigate some aspects of mitochondrial metabolism in order to gain insights on this new finding.

A phase II trial of CHOP chemotherapy followed by yttrium 90 ibritumomab tiuxetan (Zevalin) for previously untreated elderly diffuse large B-cell lymphoma patients.

BACKGROUND: A prospective, single-arm, open-label, nonrandomized phase II combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus radioimmunotherapy trial was conducted to evaluate the efficacy and safety in untreated elderly diffuse large B-cell lymphoma (DLBCL) patients. PATIENTS AND METHODS: From February 2005 to April 2006, in our institute we treated 20 eligible elderly (age > or =60 years) patients with previously untreated DLBCL using a novel regimen consisting of six cycles of CHOP chemotherapy followed 6-10 weeks later by (90)Y ibritumomab tiuxetan. RESULTS: The overall response rate to the entire treatment regimen was 100%, including 95% complete remission (CR) and 5% partial remission. Four (80%) of the five patients who achieved less than a CR with CHOP improved their remission status after radioimmunotherapy. With a median follow-up of 15 months, the 2-year progression-free survival was estimated to be 75%, with a 2-year overall survival of 95%. The (90)Y ibritumomab tiuxetan toxicity included grade > or =3 hematologic toxicity in 12 of 20 patients; the most common grade > or =3 toxic effects were neutropenia (12 patients) and thrombocytopenia (7 patients). Transfusions of red blood cells and/or platelets were given to one patient. CONCLUSION: This study has established the feasibility, tolerability, and efficacy of this regimen for elderly patients with DLBCL.

Evidence that mesothelial cells regulate the acute inflammatory response in talc pleurodesis.

Intrapleural instillation of talc is used to produce pleurodesis in cases of recurrent malignant pleural effusions. The mechanisms by which pleurodesis is produced remain unknown but may involve either injury or activation of the mesothelium. The aim of the current study was to assess the inflammatory response of pleural mesothelial cells to talc in an experimental model in rabbits. A group of 10 rabbits were injected intrapleurally with talc (200 mg.kg(-1)) and undiluted pleural fluid was collected after 6, 24 or 48 h for measurement of interleukin (IL)-8, vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-beta1. Samples of pleura were studied to assess the inflammatory infiltrate and mesothelial cell viability. The pleural fluid IL-8 concentration peaked at 6 h, whereas VEGF and TGF-beta1 concentrations increased steadily over 48 h. Immunohistochemistry for cytokeratin showed a preserved layer of mesothelial cells despite the intense inflammatory pleural reaction. In conclusion, it is proposed that the mesothelial cell, although injured by the talc, may actively mediate the primary inflammatory pleural response in talc-induced pleurodesis.

[Identification and control of workers that pose a risk to others in the health field]. / Identificazione e controllo dei lavoratori rischiosi per gli altri nelle attività sanitarie.

BACKGROUND: Working in health care increases the probability that an impaired worker be hazardous for third persons. METHODS: A literature review concerning identification, intervention, and treatment of hazardous health care workers is here reported. RESULTS: Published reports of health care worker-to-patient transmission of bloodborne infections, and papers concerning the so-called "impaired physician", have been reviewed. DISCUSSION: According to European directives on workers' health and safety, the occupational health physician charged of medical surveillance of hospital workers is often mandated to manage impaired professionals. CONCLUSIONS: Strategies for early identification, treatment and rehabilitation of impaired physicians are reviewed and suggestions for preventive action are given.

Early positron emission tomography (PET) restaging: a predictive final response in Hodgkin's disease patients.

BACKGROUND: It is important to distinguish between responders to standard treatment and non-responders Hodgkin's disease (HD) patients. PATIENTS AND METHODS: Between June 2003-September 2004, in our institute, 40 newly-diagnosed patients with advanced stage HD were consecutively treated with ABVD chemotherapy for six cycles. All these patients underwent staging/restaging: computed tomography (CT) and positron emission tomography (PET) at time 0, PET after two cycles, CT and PET after four and six cycles. RESULTS: After two cycles (PET-2), the PET was negative in 28/40 (70%), positive in 8/40 (20%), and minimal residual uptake (MRU) was present in the remaining four (10%) patients. After treatment, among eight patients who were PET-2+, seven showed refractory disease and one had relapse after 3 months. All four patients with MRU at the PET-2 became PET- during the further four cycles and, after treatment, three were in complete response (CR) and one relapsed after 5 months. All 28 PET negative patients at the PET-2 remained PET negative and all of them were in CR after treatment. CONCLUSIONS: The PET use for early (after two cycles) response assessment in HD patients is a significant step forward and has the potential to help physicians make crucial decisions about further treatment.

Predictive role of positron emission tomography (PET) in the outcome of lymphoma patients.

An extensive analysis of the reliability of positron emission tomography (PET) after induction treatment in patients with Hodgkin's disease (HD) or aggressive non-Hodgkin's lymphoma (NHL). In all, 75 untreated patients with HD (n=41) or aggressive NHL (n=34) were studied with both PET and CT scans following standard chemotherapy induction therapy (ABVD or MACOP-B) with/without radiotherapy. Histopathological analysis was performed when considered necessary. After treatment, four out of five (80%) patients who were PET(+)/CT(-) relapsed, as compared with zero out of 29 patients in the PET(-)/CT(-) subset. Among the 41 CT(+) patients, 10 out of 11 (91%) who were PET(+) relapsed, as compared with 0 out of 30 who were PET(-). The actuarial relapse-free survival (RFS) rates were 9 and 100% in the PET(+) and PET(-) subsets, respectively (P=0.00001). All five patients who were PET(+)/CT(-) underwent a lymph node biopsy: in four (80%) cases, persistent lymphoma and was confirmed at histopathological examination. Two HD patients who were PET(-)/CT(+) (with large residual masses in the mediastinum or lung) were submitted to biopsy, which in both cases revealed only fibrosis. In HD and aggressive NHL patients, PET positivity after induction treatment is highly predictive for the presence of residual disease, with significant differences being observable in terms of RFS. PET negativity at restaging strongly suggests the absence of active disease; histopathological verification is important in patients who show PET positivity.

Electronic identification of cattle: interference in the reading of ceramic bolus transponders in the presence of ruminal magnets.

The authors assess the reading performances of electronic transponders encased in ceramic boluses, utilised as identification (ID) instruments for production ruminants, and the possible influence of the magnet, which is located in the fore-stomach of ruminants. Research has been conducted in free-range Friesian dairy herds in the Teramo Province. The use of the electronic bolus to identify cattle appears to provide better guarantees than the traditional methods used and meets the requirements of identifying individual animals at the farm level. Results demonstrate how the presence of both the magnet and the ceramic bolus, equipped with a transponder, makes it difficult, and sometimes impossible, to read the code. However, the electronic ID system is the best instrument currently available. The authors confirm the validity of this method and highlight some problems that still need to be solved.

Low concentration silver nitrate pleurodesis in rabbits: optimal concentration for rapid and complete sclerosing effect.

Pleurodesis is a useful therapeutic tool when local treatment of a recurrent malignant pleural effusion or pneumothorax is needed. We have previously demonstrated that the intrapleural injection of 0.5% silver nitrate (SN) produces a significant pleurodesis, while 0.25% SN has no sclerosing effect in a rabbit model. The objective of this study was to determine the minimum concentration of SN needed to induce pleurodesis in our experimental model. One hundred twenty male New Zealand white rabbits received 0.3, 0.4, or 0.5% SN (40 animals per group) in a total volume of 2 mL instilled intrapleurally. These animals were sacrificed 3, 7, 14 or 28 days after the intrapleural injection (n = 10 animals per group), and the pleural spaces were then assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. By 28 days, all concentrations of SN had produced a pleurodesis. There was evidence of a gross pleurodesis 7 days post-injection in animals that received 0.5% SN (score of 2.8 +/- 0.2 on a scale of 0-4). After 14 days, significant pleural adhesions were evident in the groups that received 0.4 or 0.5% SN. We conclude that SN concentrations as low as 0.3% can effectively produce a pleurodesis within 28 days of intrapleural injection. However, the precocious pleurodesis development observed 7 days after the intrapleural injection of 0.5% SN suggests that this concentration may be optimal when a fast result is necessary.