Functioning and neurocognition in very early and early-life onset bipolar disorders: the moderating role of bipolar disorder type.

Defining homogeneous subgroups of bipolar disorder (BD) is a major goal in personalized psychiatry and research. According to the neurodevelopmental theory, age at onset may be a key variable. As potential trait markers of neurodevelopment, cognitive and functional impairment should be greater in the early form of the disease, particularly type 1 BD (BD I). The age at onset was assessed in a multicenter, observational sample of 4190 outpatients with BD. We used a battery of neuropsychological tests to assess six domains of cognition. Functioning was measured using the Functioning Assessment Short Test (FAST). We studied the potential moderation of the type of BD on the associations between the age at onset and cognitive and functioning in a subsample of 2072 euthymic participants, controlling for potential clinical and socio-demographic covariates. Multivariable analyses showed cognition to not be impaired in individuals with early (21-30 years) and very early-life (before 14 years) onset of BD. Functioning was equivalent between individuals with early and midlife-onset of BD II and NOS but better for individuals with early onset of BD I. In contrast, functioning was not worse in individuals with very early-onset BD I but worse in those with very early-onset BD II and NOS. Early-life onset BDs were not characterized by poorer cognition and functioning. Our results do not support the neurodevelopmental view that a worse cognitive prognosis characterizes early-life onset BD. This study suggests that functional remediation may be prioritized for individuals with midlife-onset BD I and very early life onset BD 2 and NOS.

RadioLab project: knowledge of radon gas in Italy.

RadioLab is an Italian project, addressed to school-age people, and designed for the dissemination of scientific culture on the theme of environmental radioactivity, with particular regards to the importance of knowledge of radon gas exposure. The project is a nationwide initiative promoted by the National Institute of Nuclear Physics- INFN. First tool used by the project, and of immediate impact to assess the public awareness on radon, is the administration of the survey "do you know the radon gas?". In the survey, together with the knowledge of radon and of its sources, information on personal, cultural and territorial details regarding the interviewees are also taken. Reasonably, the survey invests not only young people, but also their relatives, school workers and, gradually, the public. The survey is administrated during exhibitions or outreach events devoted to schools, but also open to the public. The survey is in dual form: printed and online. The online mode clearly leads RadioLab project even outside the school environment. Based on the results of the survey, several statistical analyses have been performed and many conclusions are drawn about the knowledge of the population on the radon risk. The RadioLab benefit and the requirement to carry on the project goals, spreading awareness of environmental radioactivity from radon, emerge. The dataset involves all twenty Italian regions and consists of 28,612 entries covering the 5-year period 2018-2022.

Radioisotopic purity and imaging properties of cyclotron-produced 99mTc using direct 100Mo(p,2n) reaction.

Evaluation of the radioisotopic purity of technetium-99m (99mTc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 (100Mo) metallic targets at low proton energies (i.e. within 15-20 MeV) is conducted. This energy range was chosen since it is easily achievable by many conventional medical cyclotrons already available in the nuclear medicine departments of hospitals. The main motivation for such a study is in the framework of the research activities at the international level that have been conducted over the last few years to develop alternative production routes for the most widespread radioisotope used in medical imaging. The analysis of technetium isotopes and isomeric states (9xTc) present in the pertechnetate saline Na99mTcO4 solutions, obtained after the extraction/purification procedure, reveals radionuclidic purity levels basically in compliance with the limits recently issued by European Pharmacopoeia 9.3 (2018 Sodium pertechnetate (99mTc) injection 4801-3). Moreover, the impact of 9xTc contaminant nuclides on the final image quality is thoroughly evaluated, analyzing the emitted high-energy gamma rays and their influence on the image quality. The spatial resolution of images from cyclotron-produced 99mTc acquired with a mini-gamma camera was determined and compared with that obtained using technetium-99m solutions eluted from standard 99Mo/99mTc generators. The effect of the increased image background contribution due to Compton-scattered higher-energy gamma rays (E γ > 200 keV), which could cause image-contrast deterioration, was also studied. It is concluded that, due to the high radionuclidic purity of cyclotron-produced 99mTc using 100Mo(p,2n)99mTc reaction at a proton beam energy in the range 15.7-19.4 MeV, the resulting image properties are well comparable with those from the generator-eluted 99mTc.

Phytotoxicity of ionic, micro- and nano-sized iron in three plant species.

Potential environmental impacts of engineered nanoparticles (ENPs) can be understood taking into consideration phytotoxicity. We reported on the effects of ionic (FeCl3), micro- and nano-sized zerovalent iron (nZVI) about the development of three macrophytes: Lepidium sativum, Sinapis alba and Sorghum saccharatum. Four toxicity indicators (seed germination, seedling elongation, germination index and biomass) were assessed following exposure to each iron concentration interval: 1.29-1570mg/L (FeCl3), 1.71-10.78mg/L (micro-sized iron) and 4.81-33,560mg/L (nano-iron). Exposure effects were also observed by optical and transmission electron microscopy. Results showed that no significant phytotoxicity effects could be detected for both micro- and nano-sized zerovalent irons, including field nanoremediation concentrations. Biostimulation effects such as an increased seedling length and biomass production were detected at the highest exposure concentrations. Ionic iron showed slight toxicity effects only at 1570mg/L and, therefore, no median effect concentrations were determined. By microscopy, ENPs were not found in palisade cells or xylem. Apparently, aggregates of nZVI were found inside S. alba and S. saccharatum, although false positives during sample preparation cannot be excluded. Macroscopically, black spots and coatings were detected on roots of all species especially at the most concentrated treatments.

The metallobiochemistry of ultratrace levels of platinum group elements in the rat.

The use of platinum, palladium and rhodium (Platinum Group Elements - PGEs) and the possibility of exposure to their ultratrace levels is increasing. In fact, the exponential development of metallic PGE-based nanoparticles (<100 nm in size) opens extraordinary perspectives in the areas of electrocatalysts and catalytic converters, magnetic nanopowders, polymer membranes, cancer therapy, coatings, plastics, nanofibres and textiles. Like other metal-based nanoparticles, exposure to PGEs nanoparticles may result in a release of ultratrace amounts of Pt, Pd, Rh ions in the body whose metabolic fate and toxicity still need to be evaluated. Furthermore, PGEs can act as allergic sensitizers by acting as haptens and inducing both type I and IV allergic reactions. In this work we studied the in vivo metabolic patterns of ultratrace levels of potent allergens and sensitizers PGE halogenated salts. (191)Pt, (103)Pd and (101m)Rh radioisotopes were prepared via cyclotron irradiation and used for radiolabelling Na2(191)PtCl4, Na2(103)PdCl4 and Na2(101m)RhCl6 salts. These anionic chlorocomplexes were intraperitoneally injected into rats (114 ng Pt kg(-1) bodyweight; 24 ng Pd kg(-1) b.w.; 16 ng Rh kg(-1) b.w.). At 16 h post-exposure, PGEs were poorly but significantly retained in all tissues analysed. Kidneys, spleen, adrenal gland, liver, pancreas and small intestine were the organs with the highest Pt, Pd, Rh concentrations. In the blood 30-35% of (103)Pd and (191)Pt and 10% of (101m)Rh were recovered in the plasma, mainly bound to albumin and to a less extent to transferrin. The hepatic and renal intracellular distribution showed the highest recovery of (191)Pt, (103)Pd and (101m)Rh in the nuclear fraction (liver) and in the cytosol (kidney). Chromatographic separation and ultrafiltration experiments on kidney and liver cytosols showed the strong ability of biochemical macromolecules to bind (191)Pt, (103)Pd and (101m)Rh, and being responsible for the retention of the three elements in the body. The link to macromolecules is the basis for the sensitizing capacity of PGEs.

Tracking of airborne radionuclides from the damaged Fukushima Dai-ichi nuclear reactors by European networks.

Radioactive emissions into the atmosphere from the damaged reactors of the Fukushima Dai-ichi nuclear power plant (NPP) started on March 12th, 2011. Among the various radionuclides released, iodine-131 ((131)I) and cesium isotopes ((137)Cs and (134)Cs) were transported across the Pacific toward the North American continent and reached Europe despite dispersion and washout along the route of the contaminated air masses. In Europe, the first signs of the releases were detected 7 days later while the first peak of activity level was observed between March 28th and March 30th. Time variations over a 20-day period and spatial variations across more than 150 sampling locations in Europe made it possible to characterize the contaminated air masses. After the Chernobyl accident, only a few measurements of the gaseous (131)I fraction were conducted compared to the number of measurements for the particulate fraction. Several studies had already pointed out the importance of the gaseous (131)I and the large underestimation of the total (131)I airborne activity level, and subsequent calculations of inhalation dose, if neglected. The measurements made across Europe following the releases from the Fukushima NPP reactors have provided a significant amount of new data on the ratio of the gaseous (131)I fraction to total (131)I, both on a spatial scale and its temporal variation. It can be pointed out that during the Fukushima event, the (134)Cs to (137)Cs ratio proved to be different from that observed after the Chernobyl accident. The data set provided in this paper is the most comprehensive survey of the main relevant airborne radionuclides from the Fukushima reactors, measured across Europe. A rough estimate of the total (131)I inventory that has passed over Europe during this period was <1% of the released amount. According to the measurements, airborne activity levels remain of no concern for public health in Europe.

Production study of high specific activity NCA Re-186g by proton and deuteron cyclotron irradiation.

Very high specific activity (A(S)) (186g)Re could be produced by either proton or deuteron cyclotron irradiation on highly enriched (186)W target in no-carrier-added (NCA) form, leading to a A(S) very close to the theoretical carrier free (CF) value of 6.88GBqmicrog(-1). Thick target yields (TTYs), obtained irradiating both thick metal W targets of natural isotopic composition and highly enriched pressed powdered (186)W targets, were measured at different particles energies taking into account high accuracy and precision on both yield and beam energy. The measurement of radionuclidic purity of (186g)Re obtained activating highly enriched (186)W by both p and d beams were also carried out and accurately compared. The excitation function as thin-target yields (tty, i.e. proportional to the reaction cross-sections) and the integrated TTYs for all Re (A=181, 182, 183, 184, 186 and their metastable levels), W and Ta co-produced radionuclides will be presented elsewhere in deep details.

Cyclotron production of 64Cu by deuteron irradiation of 64Zn.

The short-lived (12.7h half-life) (64)Cu radioisotope is both a beta(+) and a beta(-) emitter. This property makes (64)Cu a promising candidate for novel medical applications, since it can be used simultaneously for therapeutic application of radiolabelled biomolecules and for diagnosis with PET. Following previous work on (64)Cu production by deuteron irradiation of natural zinc, we report here the production of this radioisotope by deuteron irradiation of enriched (64)Zn. In addition, yields of other radioisotopes such as (61)Cu, (67)Cu, (65)Zn, (69m)Zn, (66)Ga and (67)Ga, which were co-produced in this process, were also measured. The evaporation code ALICE-91 and the transport code SRIM 2003 were used to determine the excitation functions and the stopping power, respectively. All the nuclear reactions yielding the above-mentioned radioisotopes were taken into account in the calculations both for the natural and enriched Zn targets. The experimental and calculated yields were shown to be in reasonable agreement. The work was carried out at the Scanditronix MC-40 Cyclotron of the Institute for Health and Consumer Protection of the Joint Research Centre of the European Commission (Ispra site, Italy). The irradiations were carried out with 19.5 MeV deuterons, the maximum deuteron energy obtainable with the MC-40 cyclotron.

Multidisciplinary and multisetting team management programme in heart failure patients affects hospitalisation and costing.

BACKGROUND: We evaluated whether multidisciplinary disease management programme developed with collaboration of physicians and nurses inside and outside general district hospital settings can affect clinical outcomes in heart failure population over a 12-month period. METHODS: 571 patients hospitalised with CHF were referred to our unit and 509 patients agreed to participation. The intervention team included physicians and nurses from Internal Medicine and Cardiac Dept., and the patient's general practitioners. Contacts were on a pre-specified schedule, included a computerised programme of hospital visits and phone calls; in case of NYHA functional class III and IV patients, home visits were also planned. RESULTS: The median age of patients was 77.7+/-9 years (43.3% women). At baseline the percentage of patients with NYHA class III and IV was 56.0% vs. 26.0% after 12 months (P<0.05). Programme enrolment reduced total hospital admissions (82 vs. 190, -56%, P<0.05), number of patients hospitalised (62 vs. 146, 57%, P<0.05). All NYHA functional class benefited (class I=75%, class IV=67%), with reduction in the costing (-48%, P<0.05). Improvement in symptoms (-9.0+/-3.2) and signs (-5.2+/-3.1) scores was measured (P<0.01). Therapy optimisation was obtained by 20.5% increase in patients taking betablockade and 21.0% increase in those on anti-aldosterone drugs. CONCLUSIONS: Multidisciplinary approach to CHF management can improve clinical management, reducing hospitalisation rate and costing.

On the high-resolution gamma-ray spectrometric measurement of 40K in natural and synthetic materials.

Many regulatory agencies require that all building materials and industrial waste be tested for their naturally occurring radioactive material (NORM) concentrations before they can be used or thrown away. Usually the NORM concentrations of 40K, 232Th and 238U are measured by gamma-ray spectrometry using high-purity germanium or NaI(Tl) detectors. 40K is measured through its 1460.8 keV gamma line, which is mixed with 1459.2 keV line of 228Ac from the chain of 232Th. This fact ignored till now, requires a correction in the computation of 40K concentration. Although in many cases the error is <1%, there are cases where there have been higher errors. It should be emphasised that even if the correction in 40K concentration is large, the correction of the external dose index is negligible owing to the weighing factor being higher for 232Th than for 40K (by at least a factor of 10).

Optimisation study of alpha-cyclotron production of At-211/Po-211g for high-LET metabolic radiotherapy purposes.

The production of no-carrier-added (NCA) alpha-emitter (211)At/(211g)Po radionuclides for high-LET targeted radiotherapy and immunoradiotherapy, through the (209)Bi(alpha,2n) reaction, together with the required wet radiochemistry and radioanalytical quality controls carried out at LASA is described, through dedicated irradiation experiments at the MC-40 cyclotron of JRC-Ispra. The amount of both the gamma-emitter (210)At and its long half-lived alpha-emitting daughter (210)Po is optimised and minimised by appropriate choice of energy and energy loss of alpha particle beam. The measured excitation functions for production of the main radioisotopic impurity (210)At-->(210)Po are compared with theoretical predictions from model calculations performed at ENEA.

Influence of the chemical form on the plasma clearance of ruthenium in humans.

The radioisotopes of ruthenium (103Ru and 106Ru) are abundant fission products and represent a radiological risk for the population in case of nuclear accidents. Few biokinetic studies have been performed on humans up to now and consequently the current model recommended by ICRP for ruthenium is derived mainly by extrapolation from animal data. The stable isotope 101Ru and proton activation analysis have been used to study the biokinetics of Ru in blood plasma samples taken during 8 studies in three healthy volunteers. The results obtained demonstrated that complexed Ru (in the form of citrate Ru(IV) complexes) is cleared from blood plasma very rapidly (characteristic half time of 17+/-2 min), while inorganic Ru remains longer in the systemic circulation, and is transferred to other organs and/or excreted with a biological half time of 23+/-2h. Good reproducibility of the clearance curves indicated no evidence of inter- or intra-individual variability when the same Ru solution was injected in repeated experiments to different subjects.

Stable tracer investigations in humans for assessing the biokinetics of ruthenium and zirconium radionuclides.

The interest in the biokinetics of ruthenium and zirconium in humans is justified by the potential radiological risk represented by their radionuclides. Only a few data related to the biokinetics of ruthenium and zirconium in humans are available and, accordingly, the biokinetic models currently recommended by the ICRP for these elements are mainly based on data from animal experiments. The use of stable isotopes as tracers, coupled with a proper analytical technique (nuclear activation analysis with protons) for their determination in biological samples, represents an ethically acceptable methodology for biokinetic investigations, being free from any radiation risk for the volunteer subjects. In this work, the results obtained in eight biokinetic investigations for ruthenium, conducted on a total of three healthy volunteers, and six for zirconium, performed on a total of three subjects, are presented and compared to the predictions of the ICRP models.

A re-evaluation of the biokinetics of zirconium in humans.

There is much interest in understanding the biokinetics of zirconium in humans due to the potential radiological risk represented by the radionuclide 95Zr and by its daughter 95Nb. Despite the significance of zirconium, few data are available on the actual biokinetics of zirconium in humans. Accordingly the biokinetic model currently recommended by ICRP for this element is based mainly on data from animal experiments. In this study, the use of the stable isotopes 90Zr and 96Zr as tracers has enabled the conduct of 6 biokinetic investigations in 3 healthy volunteers. These studies have provided new valuable information about intestinal absorption and kinetics in blood plasma of zirconium and have been used for the set-up of a more realistic compartmental model with possible applications for dosimetric purposes.

Comparison of therapy detection times between implantable cardioverter defibrillators with standard dual- and single-chamber pacing.

Previous implantable cardioverter defibrillators (ICDs) required patients in need of dual-chamber (DDD) pacing for improved hemodynamic status to undergo implantation of separate devices to treat bradycardia and/or ventricular arrhythmias. An investigation was conducted to verify the performance of a new ICD that combines both therapies.Sixty-nine patients at 17 European and Canadian centers were implanted with VENTAK AV models 1810/1815, ICD's that includes DDD pacing and algorithms designed to differentiate between atrial and ventricular arrhythmias. 36 of the cohort were compared to 32 patients tested at six centers with an external test device (VENTAK MINI). In both cohorts detection times were calculated for ventricular fibrillation (VF) induced at implant. The mean detection times (DT) from the VENTAK AV device were compared to the DT from the VENTAK MINI device. Patient characteristics of the VENTAK AV and the VENTAK MINI control groups were similar. Mean VF detection time (+/-SD) with the VENTAK AV device was 2.21 +/- 0.54 seconds, as compared with 1.87 +/- 0.62 seconds with the VENTAK MINI (p < 0.01), indicating that the difference in means did not exceed one second. The VENTAK AV system function did not demonstrate interaction with the pacemaker function, as indicated by the clinical significance with the detection times of the study device. The difference in detection times between cohorts did not statistically exceed one second. Appropriate detection of the new ICD was not compromised by the addition of the dual-chamber pacing therapy.

Content of trace elements in the respirable fractions of the air particulate of urban and rural areas monitored by neutron activation analysis.

The concentrations (ng/m3) of more than 30 trace elements have been determined in the total air particulate matter and in the size-segregated fractions collected in urban, industrialized, and rural residential areas in northern Italy by means of a multistage inertial impactor with the PM10 inlet. All measurements have been carried out by instrumental neutron activation analysis, except for Pb and Cd, which have been determined by electrothermal atomic absorption spectroscopy. Analytical quality assurance procedures have been developed with special regard to blanks, reagents, and sampling. Total concentrations and the granulometric distribution found in the different locations are reported and compared.

Clinical reliability of single-lead VDD pacing from evaluation of P-wave sensing under dynamic conditions.

In a group of 20 patients implanted with a single-lead VDD pacing system, a wide interindividual variability was found in P-wave amplitude changes occurring under dynamic conditions, even though they were of minor clinical relevance because constant atrial tracking was maintained.

[The efficacy of oral treatment with flecainide for paroxysmal atrial fibrillation: correlation with plasma concentration]. / Efficacia del trattamento orale con flecainide nella fibrillazione atriale parossistica: correlazione con le concentrazioni plasmatiche.

In the acute treatment of paroxysmal atrial fibrillation several drugs can be used. The aim of our work was to assess the efficacy of a single oral dose of flecainide in the conversion to sinus rhythm by correlating this data with flecainide plasma concentration. We have considered 37 patients affected by paroxysmal atrial fibrillation (for more than 8 hours) randomly assigned to the following two groups: group A, 19 patients, mean age 44.4 +/- 1.9 years) treated with flecainide (200 mg) and control group B (18 patients, mean age 46.6 +/- 1.8 years). This was done in order to point out any possible overlap between pharmacological and spontaneous conversion to sinus rhythm. In all patients, the following were performed: a Holter recording (524 hours) to evaluate the time of conversion to sinus rhythm (t-conversion to sinus rhythm), a determination of flecainide plasma concentration (after 150 flecainide administration) an Rx, an Echo-2D/Doppler test and an estimation of thyroid function. The Rx, the Echo-2D/Doppler and the endocrinological data in the 2 groups did not show any significant differences. We obtained a conversion to sinus rhythm in all but one of the group A patients (time of conversion to sinus rhythm 162 +/- 83 min) and in just 5 group B patients (time of conversion to sinus rhythm 1118 +/- 125 min) (time of conversion to sinus rhythm A vs B p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)