Enhanced-Precision Measurement of Glutathionyl Hemoglobin by MALDI-ToF MS.

Glutathionyl-hemoglobin (HbSSG) is used as a human biomarker to pinpoint systemic oxidative stress caused by various pathological conditions, noxious lifestyles, and exposure to drugs and environmental or workplace toxicants. Measurement by MALDI mass spectrometry is most frequently used, however, the method suffers from excessive uncontrolled variability. This article describes the improvement of a MALDI-ToF mass spectrometry method for HbSSG measurement through enhanced precision, based on strict control of sample preparation steps and spreadsheet-based data analysis. This improved method displays enhanced precision in the analysis of several hundred samples deriving from studies in different classes of healthy and diseased human subjects. Levels span from 0.5% (lower limit of detection) up to 30%, measured with a precision (as SE%) < 0.5%. We optimized this global procedure to improve data quality and to enable the Operator to work with a reduced physical and psychological strain. Application of this method, for which full instruction and the data analysis spreadsheet are supplied, can encourage the exploitation of HbSSG to study human oxidative stress in a variety of pathological and living conditions and to rationally test the efficacy of antioxidant measures and treatments in the frame of health promotion.

Immunotherapy treatment: an issue for metabolic response.

Since the beginning of second decade of last century, when it was introduced in many oncologic scenarios, immunotherapy has become an important tool in the management of a growing number of cancers. Immunotherapy for cancer appears to be useful, improving not only progression free survival but also overall survival, thus achieving the goal that many advanced cancers, previously considered without effective treatment options, have now become successfully treatable. However, considering the relatively recent introduction of these drugs in clinical scenarios and the continuous release of new drugs, there is a lack of large validated clinical experiences and many issues are today debated amongst which the evaluation of the response to immune-therapy. Engaging the host immune system in fighting against cancer is an energy-consuming process, requiring T-cell recruiting; this process, named "pseudo-progression," sometimes produces an increase of both dimensional and metabolic ratio of the lesions, as well as the appearance of "new lesions." This behavior, always considered as undisputed progressive disease when traditional chemotherapy is employed, should be carefully considered in the field of immunotherapy, where the phenomenon of "flare" followed by regression of the disease can occur. In this paper, Authors analyzed the best available evidence in this field, reviewed the most important issues concerning the development of immunotherapy, and addressed evidence and concerns about the evaluation of response when using immunotherapy drugs, in terms of both radiological and nuclear medicine criteria.

Validation of a new protocol for ¹8F-FDG infusion using an automatic combined dispenser and injector system.

PURPOSE: In nuclear medicine, radiopharmaceuticals are usually administered in unit doses partitioned from multi-dose vials. The partitioning typically takes place in a radiopharmacy, depending on local practice. Automatic, as opposed to manual, partitioning and administration should reduce radiation exposure of the personnel involved, improve the accuracy of the administration and mitigate contamination. This study set out to verify and validate the (18)F-fluorodeoxyglucose (FDG) administration procedure performed using Intego (MEDRAD, Inc., Warrendale, PA, USA), a combined dispenser and injector system. We considered maintenance of sterility and the system's potential to improve, with respect to the manual procedure, the accuracy of net administered (18)F-FDG radioactivity in patients and the radiation protection of operators. METHODS: A media-fill procedure was used to assess whether sterility is maintained during use of the Intego system. Simulating a typical working day's setup and use of the system, we investigated the accuracy of the net administered (18)F-FDG activity obtained with Intego versus the manual dose delivery system. We also measured personnel radiation exposure during use of Intego and during manual administration and recorded and compared environmental doses in the two conditions. RESULTS: The radiopharmaceutical remained sterile in all the tests performed. The accuracy of the net (18)F-FDG activity delivered to the patients was found to be within 3 % points, as required by European Association of Nuclear Medicine (EANM) guidelines on (18)F-FDG imaging procedures. With Intego, the residual radioactivity in the tubing was 0.20 MBq, corresponding to approximately 0.07 % of the mean activity delivered. With manual injection, the residual radioactivity in the syringe averaged 7.37 MBq, corresponding to a mean error of 2.9 % in the delivered dose. During the injection step of the positron emission tomography (PET) procedure, whole-body and extremity radiation exposures were significantly reduced with Intego by 38 and by 94 %, respectively, compared to the levels associated with manual administration (p < 0.05). CONCLUSION: Integoaccurately partitions and administers sterile doses of (18)F-FDG from multi-dose vials. Compared with standard manual (18)F-FDG administration, the new procedure with an automatic dispensing and injection system greatly reduces the extremity dose to the operator involved in the administration of the radiopharmaceutical.

Brain stimulation improves associative memory in an individual with amnestic mild cognitive impairment.

In patients with cognitive deficits, brain stimulation has been shown to restore cognition ( Miniussi et al., 2008 , Brain Stimulation, 1, 326). The aim of this study was to assess whether repetitive Transcranial Magnetic Stimulation (rTMS) could improve memory performance in an individual with amnestic Mild Cognitive Impairment (aMCI). Stimulation of the left parietal cortex increased accuracy in an association memory task, and this improvement was still significant 24 weeks after stimulation began. These findings indicate that rTMS to the left parietal cortex improved memory performance in aMCI.

Happy facial expressions impair inhibitory control with respect to fearful facial expressions but only when task-relevant.

The ability to generate appropriate responses, especially in social contexts, requires integrating emotional information with ongoing cognitive processes. In particular, inhibitory control plays a crucial role in social interactions, preventing the execution of impulsive and inappropriate actions. In this study, we focused on the impact of facial emotional expressions on inhibition. Research in this field has provided highly mixed results. In our view, a crucial factor explaining such inconsistencies is the task-relevance of the emotional content of the stimuli. To clarify this issue, we gave two versions of a Go/No-go task to healthy participants. In the emotional version, participants had to withhold a reaching movement at the presentation of emotional facial expressions (fearful or happy) and move when neutral faces were shown. The same pictures were displayed in the other version, but participants had to act according to the actor's gender, ignoring the emotional valence of the faces. We found that happy expressions impaired inhibitory control with respect to fearful expressions, but only when they were relevant to the participants' goal. We interpret these results as suggesting that facial emotions do not influence behavioral responses automatically. They would instead do so only when they are intrinsically germane for ongoing goals. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Beneficial effects of treatment with transglutaminase inhibitor cystamine on the severity of inflammation in a rat model of inflammatory bowel disease.

Inflammatory bowel disease (IBD) represents a socially and clinically relevant disorder, characterized by intestinal chronic inflammation. Cystamine (CysN) is a multipotent molecule with healthy effects and, moreover, it is an inhibitor of transglutaminases (TGs), including the TG type 2 (TG2), an enzyme with pleiotropic functions, involved in different pathways of inflammation and central in the pathogenesis of some human disorders as the IBD. Our aim was to evaluate the effect of CysN in an IBD rat model. A total of 30 rats were divided into 4 groups: controls without treatment (CTR; n=7); receiving the 2,4,6-trinitrobenzene sulfonic acid enema (TNBS group; n=8); treated with TNBS enema plus oral CysN (TNBS-CysN group; n=8); treated with CysN (CysN group; n=7). After killing, bowel inflammation was evaluated applying specific scores. TG activity, TG2 and isopeptide bond immunohistochemical expression, and tumor necrosis factor-α (TNF-α) were evaluated in the colonic tissue, such as interleukin-6 (IL-6) serological levels (ELISA). TG2 was also evaluated on the luminal side of the colon by immunoautoradiography. Colonic samples from IBD patients were compared with animal results. TNBS-CysN group developed a less severe colitis compared with the TNBS group (macroscopic score 0.43±0.78 vs 3.28±0.95, microscopic score 6.62±12.01 vs 19.25±6.04, P<0.05, respectively) associated with a decrease of TG activity, TG2 and isopeptide bond immunohistochemical expression, TNF-α and IL-6 levels. No statistically significant differences were found between CysN and CTR groups. The colonic immunolocalization of TG2 was comparable in humans affected by IBD and TNBS-administered animals. This is the first demonstration that treatment with a CysN has an anti-inflammatory effect, reducing severity of colitis in a rat model. CysN could be tested as a possible treatment or co-treatment in IBD therapeutic trials.

The when and where of spatial storage in memory-guided saccades.

The memory-guided saccade paradigm is an ideal experimental model for studying spatial working memory. Both the posterior parietal cortex and frontal cortex are known to play a role in working memory; however, there is much debate about the degree of their involvement in the retention of information. We used event-related potentials and electromagnetic tomography to clarify the precise time course and location of the neural correlates of spatial working memory during a memory-guided saccade task in humans. We observed sustained activity in the inferior parietal lobe and extrastriate areas that persisted for the entire duration of the sensory- and memory-phases. This time course reveals that these regions participate in both initial sensory processing of visual cues and in the short-term maintenance of spatial location memory. Similar sustained activation was also observed in the anterior cingulate cortex, probably reflecting attentive control during the task. Differential activity between conditions was also recorded in the dorsolateral prefrontal cortex and in the frontal eye fields, but only during the initial part of the memory-phase. This finding suggests that these areas are not involved in the storage of spatial information, but rather in response selection and in transformation of spatial information into a motor coordinate framework, respectively. By exploiting techniques that provide exquisite temporal resolution and reasonably precise anatomical localization, this study provides evidence supporting the key role of inferior parietal lobe in the storage of spatial information during a working memory guided saccade.

Potentiation of short-latency cortical responses by high-frequency repetitive transcranial magnetic stimulation.

It is generally accepted that low- and high-frequency repetitive transcranial magnetic stimulation (rTMS) induces changes in cortical excitability, but there is only indirect evidence of its effects despite a large number of studies employing different stimulation parameters. Typically the cortical modulations are inferred through indirect measurements, such as recording the change in electromyographic responses. Recently it has become possible to directly evaluate rTMS-induced changes at the cortical level using electronencephalography (EEG). The present study investigates the modulation induced by high-frequency rTMS via EEG by evaluating changes in the latency and amplitude of TMS-evoked responses. In this study, rTMS was applied to the left primary motor cortex (MI) in 16 participants while an EEG was simultaneously acquired from 29 scalp electrodes. The rTMS consisted of 40 trains at 20 Hz with 10 stimuli each (a total of 400 stimuli) that were delivered at the individual resting motor threshold. The on-line modulation induced by the high-frequency TMS was characterized by a sequence of EEG responses. Two of the rTMS-induced responses, P5 and N8, were specifically modulated according to the protocol. Their latency decreased from the first to the last TMS stimuli, while the amplitude values increased. These results provide the first direct, on-line evaluation of the effects of high-frequency TMS on EEG activity. In addition, the results provide a direct demonstration of cortical potentiation induced by rTMS in humans.

Threatening Facial Expressions Impact Goal-Directed Actions Only if Task-Relevant.

Facial emotional expressions are a salient source of information for nonverbal social interactions. However, their impact on action planning and execution is highly controversial. In this vein, the effect of the two threatening facial expressions, i.e., angry and fearful faces, is still unclear. Frequently, fear and anger are used interchangeably as negative emotions. However, they convey different social signals. Unlike fear, anger indicates a direct threat toward the observer. To provide new evidence on this issue, we exploited a novel design based on two versions of a Go/No-go task. In the emotional version, healthy participants had to perform the same movement for pictures of fearful, angry, or happy faces and withhold it when neutral expressions were presented. The same pictures were shown in the control version, but participants had to move or suppress the movement, according to the actor's gender. This experimental design allows us to test task relevance's impact on emotional stimuli without conflating movement planning with target detection and task switching. We found that the emotional content of faces interferes with actions only when task-relevant, i.e., the effect of emotions is context-dependent. We also showed that angry faces qualitatively had the same effect as fearful faces, i.e., both negative emotions decreased response readiness with respect to happy expressions. However, anger has a much greater impact than fear, as it increases both the rates of mistakes and the time of movement execution. We interpreted these results, suggesting that participants have to exploit more cognitive resources to appraise threatening than positive facial expressions, and angry than fearful faces before acting.

The ideal marker for measuring GFR: what are we looking for?

INTRODUCTION: The most accurate way of assessing kidney function is the measurement of the glomerular filtration rate (GFR). Since, we do not have good formulae to estimate GFR in elderly, in this study we  evaluate the accuracy of the most commonly used formulas for the estimation of GFR in comparison with direct measurement in elderly. MATERIALS AND METHODS: 85 patients (51 males and 34 females), with an average age of 76.2 ± 4.4 years, 42% already diagnosed with chronic kidney disease (CKD) were investigated. Two plasma samples were collected between  60-90 and 165-195 minutes after injection of 99mTc-DTPA, and the GFR was calculated applying Charles D. Russell's two-sample method. RESULTS: When comparing the GFR values obtained from the various formulae by creatinine levels with the GFR values obtained by measuring 99mTc-DTPA residue, the following concordance values emerged: (1) MDRD: 57.5 ± 9.59 %; (2) Cockroft-Gault: 48.33 ± 24.93; (3) CKD-EPI: 49.40 ± 26.30; (4) BIS1: 58 ± 6.79. CONCLUSION: Our data shows a greater concordance between the GFR values calculated with the Russell's method and the estimated values of GFR when the latter are calculated using the MDRD or BIS1 formulae.

Removal of radioisotopes in solution and bactericidal/bacteriostatic sterilising power in activated carbon and metal silver filters.

Activated carbon filters play an important role in water filtration and purification from contaminants of different origin. Their limit consists in bacterial proliferation, which may occur only during prolonged periods of non-use and in their ability to remove radioactive contaminants present in waste water from Industry or Nuclear Medicine departments. In this work we tested a commercially available activated carbon filter for water purification enriched with silver plated parts incubating in static condition at room temperature different micro organisms (Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis, Staphylococcus aureus, Aspergillum niger), up to 78 days. The microbial growth was in general more inhibited in the presence of metal silver into the activated carbon in respect to filters with the activated carbon alone: >4log inhibition of bacterial proliferation after 78 days of incubation the presence of silver vs. 2log without silver. When the filters were incubated empty of carbon, the sterilizing power of silver was confirmed further. The activated carbon filters proved also their ability in removing from water the principal radioisotopes used for residues liquid medical and research purposes ((131)I, (99m)Tc, (201)Tl, (67)Ga). These results contribute useful data for the use of the silver-enriched carbon filters in water filtration both for daily use at home, and professional use in a Nuclear Medicine laboratory.

Visuospatial Attention and Saccadic Inhibitory Control in Children With Cerebral Palsy.

Cerebral palsy (CP) is a non-progressive syndrome due to a pre-, peri- or post-natal brain injury, which frequently involves an impairment of non-motor abilities. The aim of this article was to examine visuospatial attention and inhibitory control of prepotent motor responses in children with CP showing a normal IQ or mild cognitive impairment, measuring their performance in oculomotor tasks. Ten children (9-16-year-old) with spastic CP and 13 age-matched, typically developing children (TDC) participated in the study. Subjects performed a simple visually-guided saccade task and a cue-target task, in which they performed a saccade towards a peripheral target, after a non-informative visual cue was flashed 150 ms before the imperative target, either at the same (valid) or at a different (invalid) spatial position. Children with CP showed severe executive deficits in maintaining sustained attention and complying with task instructions. Furthermore, saccadic inhibitory control appeared to be significantly impaired in the presence of both stimulus-driven and goal-directed captures of attention. In fact, patients showed great difficulties in suppressing saccades not only to the cue stimuli but also to the always-present target placeholders, which represented powerful attentional attractors that had to be covertly attended throughout the task execution. Moreover, impairment did not affect in equal manner the whole visual field but showed a marked spatial selectivity in each individual subject. Saccade latencies in the cue-target task were faster in the valid than in the invalid condition in both child groups, indicating the preservation of low-level visuospatial attentive capabilities. Finally, this study provides evidence that these impairments of executive skills and in inhibitory control, following early brain injuries, manifest in childhood but recover to virtually normal level during adolescence.

Pursuit eye movements involve a covert motor plan for manual tracking.

When we make an aiming movement toward a moving visual object, eye-hand coupling is of paramount importance for accurate motor performance. Some studies have suggested that both gaze and manual tracking control systems are driven by a common command signal. However, it has never been demonstrated that a motor plan for the arm is produced even when the object is tracked by the eyes alone. By applying transcranial magnetic stimulation to the motor cortex, we show for the first time that ocular tracking is linked to an overall decrease in the excitability of the motor control system of the relaxed upper limb, as estimated from the amplitude of the motor evoked potentials recorded in contralateral hand and wrist muscles. Furthermore, this reduced excitability is modulated in a manner compatible with a subthreshold neural activation encoding a manual tracking response to the same target pursued by the eyes. In addition, excitability changes are contingent on upper-limb posture, because they are present only with a pronated forearm and not with a supinated hand position. We provide direct evidence that, if the arm is held in a congruent postural configuration, tracking a moving object always entails a coordinated motor plan, which involves both gaze and hand movements. Active inhibitory mechanisms are activated to prevent an overt arm movement, whenever a manual tracking is not requested. Our data provide strong evidence in favor of the existence of a common drive to both eye and hand tracking systems.

Evaluation of different counting methods for use in radiochemical purity testing procedures for 99mTc-labelled radiopharmaceuticals.

The efficiency and accuracy of different methods for quality control of radiopharmaceutical preparations for diagnostic purpose were studied. The radiochemical purity of (99m)Tc Tetrafosmin, (99m)Tc Exametazime, (99m)Tc Sestamibi and (99m)Tc Oxidronate was evaluated by different thin layer chromatography systems, followed by cutting of the strips into two or three sections and by the measurement of radioactivity distribution by dose calibrator or gamma counter. In addition, to confirm the accuracy of these routine procedures, the strips were cut into a number of micro-sections (14-25) and each of them evaluated by the gamma counter. The three tested procedures gave similar results and revealed a good and comparable accuracy. The radioactivity measurement with the dose calibrator remains the most practicable because of the rapidity of execution.

Resveratrol sensitization of DU145 prostate cancer cells to ionizing radiation is associated to ceramide increase.

Radiotherapy is an established therapeutic modality for prostate cancer. Since it is well known that radiotherapy is limited due to its severe toxicity towards normal cells at high dose and minimal effect at low dose, the search for biological compounds that increase the sensitivity of tumors cells to radiation may improve the efficacy of therapy. Resveratrol, a natural antioxidant, was shown to inhibit carcinogenesis in animal models, and to block the process of tumor initiation and progression. The purpose of this study was to examine whether or not resveratrol can sensitize DU145, an androgen-independent human prostate cancer cell line, to ionizing radiation. We report here that DU145 cells are resistant to ionizing radiation-induced cell death, but pretreatment with resveratrol significantly enhances cell death. Resveratrol acts synergistically with ionizing radiation to inhibit cell survival in vitro. Resveratrol also potentiates ionizing radiation-induced ceramide accumulation, by promoting its de novo biosynthesis. This confirms ceramide as an effective mediator of the anticancer potential induced by resveratrol.

Event-related power modulations of brain activity preceding visually guided saccades.

To analyze the characteristics of the event-related desynchronization (ERD) and synchronization (ERS) of cortical rhythms during the preparation and execution of a lateralized eye movement, EEG was recorded in normal subjects during a visually guided task. Alpha and beta bands were investigated in three temporal intervals: a sensory period, a delay period and a saccade preparation period time locked with saccade onset. Modulations of ERD/ERS power, coupled with the task, reached the largest amplitudes over the frontal and parieto-occipital regions. Differences of oscillatory activity in the alpha bands revealed an intriguing pattern of asymmetry in parieto-occipital areas. Rightward saccades induced a larger desynchronization with respect to the leftward saccades in the left hemisphere, but not in the right. If representative, these findings are congruent to the established right-hemisphere dominance of the brain areas that direct attention. Moreover differences between the two alpha types emerged in the frontal areas before and during the saccade preparation periods, indicative of differential engagement of these areas depending on the task demands. In conclusion, the present approach shows that planning eye movements is linked with covert orienting of spatial attention and may supply a useful method for studying eye movements and selective attention-related processes.

Abnormalities of homocysteine and B vitamins in the nephrotic syndrome.

INTRODUCTION: The nephrotic syndrome is associated with heightened risk for arterial and venous thrombosis. Multiple derangements of hemostasis and acquired risk factors such as hyperlipidemia and hypertension contribute to this risk. The prevalence in the nephrotic syndrome of high circulating levels of homocysteine and of low levels of the B vitamins that are involved in its metabolism, which may play a role in thrombosis, is not well defined. MATERIALS AND METHODS: In 84 patients with nephrotic syndrome and 84 sex- and age-matched controls, hemostasis variables and the circulating levels of total homocysteine (tHcy), vitamin B(6), B(12) and folates were measured. RESULTS: tHcy levels were higher, vitamin B(6) and vitamin B(12) levels were lower in nephrotic patients than in controls. The association of low vitamin B(6) levels with the nephrotic syndrome was independent of any other alteration associated with the disease. Eighty-two percent of patients with the nephrotic syndrome had vitamin B(6) levels falling in the lowest quartile of the normal distribution. Antithrombin deficiency, factor V Leiden, antiphospholipid antibodies, hypertension, dyslipidemia, were more frequent in patients with the nephrotic syndrome than in controls. CONCLUSIONS: Patients with the nephrotic syndrome have multiple risk factors for thrombosis. We report that they frequently have low circulating levels of vitamin B(6), which associate with a heightened risk for venous and arterial thrombosis.

Dynamic Changes in Upper-Limb Corticospinal Excitability during a 'Pro-/Anti-saccade' Double-Choice Task.

Under natural behavioral conditions, visually guided eye movements are linked to direction-specific modulations of cortico-spinal system (CSS) excitability in upper-limb muscles, even in absence of a manual response. These excitability changes have been shown to be compatible with a covert motor program encoding a manual movement toward the same target of the eyes. The aim of this study is to investigate whether this implicit oculo-manual coupling is enforced following every saccade execution or it depends on the behavioral context. Twenty-two healthy young adults participated in the study. Single-pulse transcranial magnetic stimulation was applied to the motor cortex at nine different time epochs during a double-choice eye task, in which the decision to execute a prosaccade or an antisaccade was made on the color of a peripheral visual cue. By analyzing the amplitude of the motor evoked potentials (MEP) in three distal muscles of the resting upper-limb, a facilitation peak of CSS excitability was found in two of them at 120 ms before the eyes begin to move. Furthermore, a long-lasting, generalized reduced corticomotor excitability develops following the eye response. Finally, a quite large modulation of MEP amplitude, depending on the direction of the saccade, is observed only in the first dorsal interosseous muscle, in a narrow time window at about 150 ms before the eye movement, irrespective of the type of the ocular response (pro-/anti-saccade). This change in CSS excitability is not tied up to the timing of the occurrence of the visual cue but, instead, appears to be tightly time-related to the saccade onset. Observed excitability changes differ in many respects from those previously reported with different behavioral paradigms. A main finding of our study is that the implicit coupling between eye and hand motor systems is contingent upon the particular motor set determined by the cognitive aspects of the performed oculomotor task. In particular, the direction-specific modulation in CSS excitability described in this study appears to be related to perceptual and decision-making processes rather than representing an implicit upper-limb motor program, coupled to the saccade execution.

Quality control on radiochemical purity in Technetium-99m radiopharmaceuticals labelling: three years of experience on 2280 procedures.

OBJECTIVE: the purpose of this study was to offer an example of evaluations of the ISO9001 certified internal quality assurance (QA) system of 99mTc-radiopharmaceutical preparations and quality control in vivo use, using industrial kits and generators in order to identify possible sources of errors in the procedures labeling and quality control procedures. METHODS: The study was performed at a single institution over a period of three years (July 1st, 2011 - July 1st, 2014), and included a total of 2280 radiopharmaceutical preparations prepared by four different technologists. All the radiopharmaceutical preparations and quality controls were performed according to each SPC provided by the manufacturer. The radiopharmaceutical preparations were the following (trade names are reported in brackets): 99mTc-albumin colloid [Nanocoll] (n=349), 99mTc-oxidronate [Technescan®hdp] (n=701), 99mTc-exametazime [Ceretec] (n=169), 99mTc-sestamibi [Cardiolite] (n=92), 99mTc-albumin aggregated [Technescan®lyomaa] (n=140), 99mTc-tetrofosmin [Myoview]) (n=567), 99mTc-diethylene triamine pentacetic acid [Technescan®dtpa] (n=254), and 99mTc-dimercapto succinic acid [Renocis®] (n=8). Data were analyzed to determine the number and type of radiopharmaceutical labelling failure and to derive the sources of these failures to define corrective actions and optimize the quality assurance program. RESULTS: A total of 2280 procedures were performed and recorded. Following the quality control procedure six out of the 2280 preparations (0.26%) were non-conforming for clinical use with the RCP limits indicated in the SPC. Five of these were due to gross technical errors in measurements and manual procedures and were immediately repeated, returning within the limits of acceptability. The sixth failure was due to short incubation time, though compliant with the manufacturer's instructions. CONCLUSIONS: We concluded that the quality of the final product depends on a controlled production system based on the implementation of specific standard operating procedures (ISO9001, SOP) for each radiopharmaceutical production, according to strict adherence to the SPC of each radiopharmaceutical. Based on these conclusions, in our opinion every quality control suggesting a possible error in the synthesis procedure recommended in the SPC should be immediately reported to the manufacturer, for a revision of the SPC, as well as to the regulatory agencies for an alert. This strategy may in fact allow the continuous improvement of the labelling procedures and therefore the optimization of the quality control procedures frequency to ensure both patients safety and a more rational management of resources for economic sustainability.

Covert preparation of a manual response in a 'go'/'no-go' saccadic task is driven by execution of the eye movement and not by visual stimulus occurrence.

It has been recently demonstrated that visually guided saccades are linked to changes in muscle excitability in the relaxed upper limb, which are compatible with a covert motor plan encoding a hand movement toward the gaze target. In this study we investigated whether these excitability changes are time locked to the visual stimulus, as predicted by influential attention models, or are strictly dependent on saccade execution. Single-pulse transcranial magnetic stimulation was applied to the motor cortex at eight different time delays during a 'go'/'no-go' task, which involved overt or covert orienting of attention. By analyzing the time course of excitability in three hand muscles, synchronized with the onset of either the attentional cue or the eye movement, we demonstrated that side- and muscle-specific excitability changes were strictly time locked to the saccadic response and were not correlated to the onset of the visual attentive stimulus. Furthermore, muscle excitability changes were absent following a covert shift of attention. We conclude that a sub-threshold manual motor plan is automatically activated by the saccade decision-making process, as part of a covert eye-hand coordination program. We found no evidence for a representation of spatial attention within the upper limb motor map.