The proactive self-control of actions: Time-course of underlying brain activities.

Proactive brain control optimizes upcoming actions and inhibits unwanted responses. In the present event-related potential (ERP) study, participants freely decided in advance whether to respond or not to an upcoming stimulus, then prepared or not the action according to their decision; finally, a stimulus was delivered, and subjects had to respond (or not). During the decision-making stage, a prefrontal negativity raised bilaterally in case no-response was decided, reflecting the first brain signal of proactive inhibition. Simultaneously, slow activity raised over premotor cortices independently from the decision taken, and then raised during the preparation phase only in the case of response decision (as a sort of accelerator). When the decision was not to respond, the prefrontal activity remained sustained (as a sort of brake) and showed a right-lateralized distribution during the preparation phase. Overall, we described the time-course of a proactive accelerating-braking system regulating self-control of actions.

C-C coupling between trinitrothiophenes and triaminobenzenes: zwitterionic intermediates and new all-conjugated structures.

The reactions of 1,3,5-triaminobenzene derivatives with 2,3,4-trinitrothiophene and 2-bromo-3,4,5-trinitrothiophene gave new all-conjugated compounds bearing both an electron-withdrawing and an electron-donor moiety on the same unit. The reactions with 2,3,4-trinitrothiophene offered evidence, by NMR spectroscopy at low temperature, of the formation of new labile Wheland-Meisenheimer intermediates whereas at room temperature stable unexpected products derived from the attack of the nucleophile at C-4 with replacement of the nitro group were isolated. Their formation caused, in turn, the obtainment of a salt between 1-nitroso-2,4,6-triaminobenzenes and 2,4-dinitrothiophen-3-ol. The reactions with 2-bromo-3,4,5-trinitrothiophene produced in good yields the SNAr substitution product with the displacement of the bromide. All the new coupling products obtained are of applicative interest, considering the increasing concern for highly conjugated π-systems in solar energy conversion or optoelectronic devices.

Environmental analysis of sunflower production with different forms of mineral nitrogen fertilizers.

Environmental profiles of mineral nitrogen fertilizers were used to evaluate the environmental disturbances related to their use in cultivation systems in Europe. Since the production of mineral fertilizers requires a large amount of energy, the present study of bioenergy systems is relevant in order to achieve crop yields less dependent on fossil fuels and to reduce the environmental impact due to fertilization. In this study, the suitability of the LCA methodology to analyze the environmental impact of sunflower cultivation systems with different forms of mineral nitrogen fertilizers urea and ammonium nitrate was investigated. Effects on climate change were estimated by the use of Ecoinvent 2.2 database default value for soil N2O emission factor (1%) and local emission data (0.8%) of mineral nitrogen applied to soils. LCA analysis showed a higher impact on environmental categories (human health and ecosystem quality) for the system in which urea was used as a nitrogen source. Use of urea fertilizer showed a higher impact on resource consumption due to fossil fuel consumption. Use of mineral nitrogen fertilizers showed a higher environmental burden than other inputs required for sunflower cultivation systems under study. Urea and ammonium nitrate showed, respectively, a 7.8% and 4.9% reduced impact of N2O as greenhouse gas by using direct field data of soil N2O emission factor compared to the default soil emission factor of 2006 IPCC Guidelines. Use of ammonium nitrate as mineral nitrogen fertilizer in sunflower cultivation would have a lower impact on environmental categories considered. Further environmental analysis of available technologies for fertilizer production might be also evaluated in order to reduce the environmental impacts of each fertilizer.

High levels of mid-regional proadrenomedullin in ARDS COVID-19 patients: the experience of a single, Italian Center.

OBJECTIVE: This study evaluated the ability of mid-regional proadrenomedullin (MR-proADM) to identify disease severity in Coronavirus disease 2019 (COVID-19) patients in comparison to conventional inflammatory biomarkers and clinical scores. PATIENTS AND METHODS: In an observational trial, COVID-19 acute respiratory distress syndrome (ARDS) patients were enrolled. MR-proADM, C-reactive protein (CRP), procalcitonin (PCT) and lactic acid (LA) were measured in all patients at admission (T0), at 24 hours (T1) and in the third (T3) and fifth day (T5) of hospitalization. The aims of this study were to determine the role of MR-proADM to detect patients with high risk of mortality and compare the prognostic value of MR-proADM with commonly used clinical scores (Sequential Organ Failure Assessment score - SOFA score, Acute Physiologic Assessment and Chronic Health Evaluation II score - APACHE II score, and Simplified Acute Physiological score II - SAPS II score). RESULTS: Twenty-one COVID-19 ARDS patients admitted to the Intermediate Care Unit (IMCU) were enrolled. The median MR-proADM values were 2.28, 2.41, 1.96 and 1.89 nmol/L at T0, T1, T3 and T5, respectively. The 30-day all-cause mortality rate was 52.4%. Mean MR-proADM T0 value was significantly higher in non-survivors compared with survivors (3.5 vs. 1.1 nmol/L, p < 0.05). No significant differences were found for the other inflammatory biomarkers. In terms of the area under the receiver-operating characteristic curve (AUC), MR-proADM showed a similar discriminatory power compared with APACHE II, SOFA and SAPS II score (0.81, 0.91, 0.70 and 0.78, respectively). The optimal MR-proADM cut-point cut-off point was 1.07 nmol/L, which corresponds to a sensitivity of 91% and a specificity of 71%. CONCLUSIONS: MR-proADM, in addition to the clinical scores, could be useful to predict outcome in COVID-19 ARDS patients.

Females are more proactive, males are more reactive: neural basis of the gender-related speed/accuracy trade-off in visuo-motor tasks.

In the present study, we investigated neural correlates associated with gender differences in a simple response task (SRT) and in a discriminative response task (DRT) by means of event-related potential (ERP) technique. 120 adults participated in the study, and, based on their sex, were divided into two groups matched for age and education level. Behavioral performance was assessed with computing response speed, accuracy rates and response consistency. Pre- and post-stimulus ERPs were analyzed and compared between groups. Results indicated that males were faster than females in all tasks, while females were more accurate and consistent than males in the more complex tasks. This different behavioral performance was associated with distinctive ERP features. In the preparation phase, males showed smaller prefrontal negativity (pN) and visual negativity (vN), interpreted as reduced cognitive preparation to stimulus occurrence and reduced reliance on sensory proactive readiness, respectively. In the post-stimulus phase, gender differences were present over occipital (P1, N1, P2 components) and prefrontal (pN1, pP1, pP2 components) areas, suggesting allocation of attentional resources at distinct stages of information processing in the two groups. Overall, the present data provide evidence in favor of a more proactive and cautious cognitive processing in females and a more reactive and fast cognitive processing in males. In addition, we confirm that (1) gender is an important variable to be considered in ERP studies on perceptual processing and decision making, and (2) the pre-stimulus component analysis can provide useful information concerning neural correlates of upcoming performance.

Modality-specific sensory readiness for upcoming events revealed by slow cortical potentials.

Human brain activity allows to anticipate future events and to prepare the next action accordingly; consistently, event-related potential (ERP) studies found action preparatory brain activities in the premotor and prefrontal cortex. In the present study, we investigated the preparatory activity in the sensory cortical regions. Slow cortical potentials were recorded during passive tasks, i.e., subjects expected for a sensory stimulus and no motor or cognitive response were required. In particular, we tested the hypothesis that perceptual anticipatory cortical mechanisms were modality specific. Three groups of 21 young adults underwent passive perceptual tasks in different sensory modalities (visual, auditory, or somatosensory). We confirmed the presence of a visual negativity (vN) component for the visual modality starting about 800 ms before stimulus with source in extrastriate areas and we found novel modality-specific sensory readiness components for the auditory and somatosensory modalities. The auditory positivity (aP) started about 800 ms before stimulus with source in bilateral auditory cortices and the somatosensory negativity (sN) started about 500 ms before stimulus with source in the somatosensory secondary cortex, contralateral to the stimulated hand. The scalp topography and intracranial sources of these three slow preparatory activities were mirrored with inverted polarity at early post-stimulus stage evoking the well-known visual P1, auditory N1, and somatosensory P100 components. Present findings contribute to widening the family of slow wave preparatory components, providing evidence about the relationship between top-down and bottom-up processing in sensory perception.

Coagulation activation in autoimmune bullous diseases.

The main autoimmune blistering skin disorders are pemphigus vulgaris (PV) and bullous pemphigoid (BP). They differ in the inflammatory infiltrate, which is more intense in BP. Inflammation is known to activate coagulation in several disorders. Local and systemic activation of coagulation was evaluated in BP and PV. We studied 20 BP patients (10 active and 10 remittent), 23 PV patients (13 active and 10 remittent) and 10 healthy subjects. The coagulation markers prothrombin fragment F1+2 and D-dimer were measured by enzyme-immunoassays in plasma. The presence of tissue factor (TF), the main initiator of blood coagulation, was evaluated immunohistochemically in skin specimens from 10 patients with active PV, 10 patients with active BP and 10 controls. Plasma F1+2 and D-dimer levels were significantly high in active BP (P = 0.001), whereas in active PV the levels were normal. During remission, F1+2 and D-dimer plasma levels were normal in both BP and PV. TF immunoreactivity was found in active BP but neither in active PV nor in normal skin. TF reactivity scores were higher in active BP than in controls or active PV (P = 0.0001). No difference in TF scores was found between active PV and controls. BP is associated with coagulation activation, which is lacking in PV. This suggests that BP but not PV patients have an increased thrombotic risk. The observation that thrombotic complications occur more frequently in BP than in PV further supports this view.

Visual receptive fields in the cat's retina: complications.

Visual receptive fields have been mapped with moving patterns in the cat's retinal ganglion cells. A small, general-purpose computer was used to collect a matrix of 2500 data points covering a 25 degrees -by-25 degrees region of space. The analysis of 40 units reveals the existence of many nonconcentric receptive fields and also the presence of line and edge detectors.

Plasticity: the mirror of experience.

A simple avoidance training procedure during early development produces massive neural traces in visual and somatic cortices of kittens reared in a normal environment. A preponderance of cells in these areas had response preferences for the stimuli used during training. Furthermore, some of these cells exhibited properties never found in normal animals not receiving such training. It appears that, even in an environment in which many other stimuli are present, some early experiences powerfully affect brain development and the way in which other experiences exert their effect.

Visual experience modifies distribution of horizontally and vertically oriented receptive fields in cats.

Cats were raised from birth with one eye viewing horizontal lines and one eye viewing vertical lines. Elongated receptive fields of cells in the visual cortex were horizontally or vertically oriented-no oblique fields were found. Units with horizontal fields were activated only by the eye exposed to horizontal lines; units with vertical fields only by the eye exposed to vertical lines.

Electrocortical correlates of stimulus response and reinforcement.

Three patterns of electrical response were identified in the occipital cortex of rhesus monkeys making a differential discrimination: an input pattern that identifies which stimulus has been displayed; a reinforcement pattern that indicates whether the outcome of the differential response was rewarded or in error; and an intention pattern that occurs prior to the response and predicts which response the monkey is about to make. Neither the reinforcement nor the intention pattern is present while the monkeys perform at chance; at this time, only the differences due to input can be distinguished. These results suggest that more than simple input transmission is occurring in the primary visual mechanism. The influence of the experience of the organism is apparently encoded in the averaged electrical potentials recorded from the striate cortex.

Herpes simplex virus infection and pemphigus.

Pemphigus is a group of autoimmune blistering diseases of the skin and/or mucous membranes caused by the presence of antibodies against adhesion molecules on the cell surface of keratinocytes. In genetically predisposed patients, several factors, including drugs, physical agents, neoplasms, hormones, and viruses, notably herpes simplex virus (HSV), have been hypothesized to trigger or exacerbate the disorder. To clarify whether HSV infection represents an aetiopathogenetic factor for pemphigus or a consequence of the immunosuppressive treatment, skin and/or mucosal swabs from 35 patients with pemphigus vulgaris or pemphigus foliaceus were tested for HSV by polymerase chain reaction. Twenty-three of these patients were newly diagnosed, while the remaining 12 had had a previous diagnosis and were under treatment with low-dosage oral corticosteroids. Repeat swabs were taken two weeks after starting intensive immunosuppressive therapy in 8 HSV-negative patients. All skin swabs (n=27) resulted negative for both HSV-1/2, while oral swabs (n=30) were positive for HSV-1 in 5 out of the 12 patients who were being treated with oral corticosteroids, but in none (n=19) of the non-treated group (p=0.0067, X2 test). Five out of the 8 patients with repeat swabs became positive for HSV-1, prompting us to start antiviral therapy. In conclusion, HSV is unlikely to be a triggering factor for pemphigus, but its presence in pemphigus lesions seems to be a frequent and early complication of immunosuppression.

Localized erosive pustular dermatosis of the scalp at the site of a cochlear implant: successful treatment with topical tacrolimus.

Erosive pustular dermatosis of the scalp (EPDS) is a rare form of nonmicrobial pustulosis mainly occurring in elderly patients with long-term sun damage to the skin. Clinically, it is characterized by pustular lesions that progressively merge into erosive and crusted areas over the scalp. The histology of EPDS is nonspecific, and its pathophysiology remains undetermined, with various types of local trauma possibly acting as the triggering factor. We describe a 24-year-old woman who developed EPDS after cochlear implant surgery for profound sensorineural hearing loss. We speculate that either the cutaneous surgery during cochlear implantation or the skin inflammation that commonly occurs near the magnet might have triggered the disorder. It is of note that the patient's skin lesions healed completely after treatment with topical tacrolimus, a relatively novel immunosuppressive molecule. Thus, topical tacrolimus may be indicated as a therapeutic alternative to the widely used steroids for this disease, mainly to avoid steroid-related cutaneous atrophy.

A histochemical approach to the evaluation of the in vivo cytotoxicity of the nitrobutadienes (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene and methyl (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate in mice liver and kidney.

Two new molecules (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene (1-Naph-DNB) and (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate (1-Naph-NMCB) in previous studies showed interesting antiproliferative activity in vitro. Furthermore, toxicological tests and histological analysis provided promising results, in particular for 1-Naph-NMCB that displayed lower toxic activity both in terms of lethal effect and tissue damage of the main organs. Finally, studies of the antitumour activity in vivo confirmed the efficacy of both molecules, though with some differences in tumour selectivity and levels of activity. In this investigation the activities of some specific enzymes, acid phosphatase (AcPase), alkaline phosphatase (AlkPase), catalase (Cat), succinic dehydrogenase (SDH), glucose-6-phosphatase (G6Pase) and K+ p-nitrophenyl phosphatase (K+ pNPPase) were studied in the liver and kidney as histopathological biomarkers, to assess the effects of the two compounds in organs generally involved in the metabolism and excretion of different drugs. As oxidative stress may also develop as a consequence of the toxic effect of chemicals, reactive oxygen species (ROS) production was evaluated by a histochemical method. The results indicated that some enzyme activities and ROS expression changed in a dose-related manner. Nevertheless, neither in the liver nor in the kidney were dramatic toxic effects evident. By contrast, the variations of some enzyme activities (AlkPase, AcPase, Cat, K+ pNPPase) were interpreted as possible defensive mechanisms for tolerating high dosage of the compounds.

Beyond the "Bereitschaftspotential": Action preparation behind cognitive functions.

Research on preparatory brain processes taking place before acting shows unexpected connections with cognitive processing. From 50 years, we know that motor-related brain activity can be measured by electrocortical recordings 1-3s before voluntary actions. This readiness potential has been associated with increasing excitably of premotor and motor areas and directly linked to the kinematic of the upcoming action. Now we know that the mere motor preparation is only one function of a more complex preparatory activity. Recent research shows that before any action many cognitive processes may occur depending on various aspects of the action, such as complexity, meaning, emotional valence, fatigue and consequences of the action itself. In addition to studies on self-paced action, the review considers also studies on externally-triggered paradigms showing differences in preparation processes related to age, physical exercise, and task instructions. Evidences from electrophysiological and neuroimaging recording indicate that in addition to the motor areas, the prefrontal, parietal and sensory cortices may be active during action preparation to anticipate future events and calibrate responses.

Comparative life cycle assessment study on environmental impact of oil production from micro-algae and terrestrial oilseed crops.

In this study the LCA methodology is applied in order to satisfy two goals: i) to evaluate the hot spots in site-specific production chain of biodiesel from terrestrial and micro-algae feedstock; ii) to compare quantitatively, utilizing primary data, the impacts of the first generation in respect to the third generation bio-fuels. Results show that micro-algae are neither competitive yet with traditional oil crops nor with fossil fuel. The use of renewable technologies as photovoltaics and biogas self production might increase the competitiveness of micro-algae oil. Further investigations are however necessary to optimize their production chain and to increase the added value of co-products.

Acoustic analysis of voice in patients treated by reconstructive subtotal laryngectomy. Evaluation and critical review.

Aim of this investigation was to analyse the voice in a group of 20 patients submitted to supracricoid partial laryngectomy (cricohyoidopexy, sparing two arytenoids) by the Multi Dimensional Voice Programme acoustic analysis system. Results revealed the following sound characteristics: high rate of noise, lack of periodic component of the signal, high rate of segments with no sound signal, vocal segments with marked air-turbulent flow, variation amplitude and frequency coefficients doubled compared to normal values, average fundamental frequency, if present, extremely variable and unsteady. These results show that the phonatory ability of the residual larynx, due to the altered anatomo-physiology of the structure after surgery, has to be completely re-estimated. In fact, the residual larynx determines a definitely reduced periodic acoustic signal, rich in noise and which can not be modulated. Good phonatory results of this treatment are basically due to preservation of a still understandable (but not perfect!) speech which, by ensuring the subjects' speech ability, overcomes and has little influence on the really poor quality of the vocal signal in these patients. However, the patient obtains a "new voice" as far as concerns acoustic features and this is very important for communication and social life. Moreover, the possibility of objectively estimating acoustic vocal function ability allows monitoring of the trend and results of possible speech therapy and/or phonosurgical rehabilitation treatment which should start from new anatomical and physiological bases, as well as from the new physical acoustic mechanism of signal production.

New insights into old waves. Matching stimulus- and response-locked ERPs on the same time-window.

We compared the effect of locking the event-related potentials (ERPs) on the stimulus vs. the response in a simple (SRT) and in a discriminative (DRT, equally probable Go/No-go) visuo-motor task. The accurate alignment of stimulus- and response-locked ERPs on the same time scale was obtained selecting a group of 27 participants with low inter-individual response time (RT) variation in the two tasks to reduce the jitter of RTs. Two-second epochs were defined for the analyses based on averaged RTs in the two tasks. Results show that the preparatory pre-stimulus activities (i.e., the pN and the BP components) were not affected by the different locking in both SRT and DRT. As expected, the exogenous post-stimulus P1 and N1 components (and the P2, present only in SRT) were larger in stimulus- than response-locked averaging; the same trend was observed for the less-known prefrontal N1 and P1 components (pN1 and pP1) that were larger in stimulus-locked averaging (the effect was not significant in SRT). The prefrontal pP2 component was only present in DRT peaking around 370 ms, and did not show an effect of locking. The frontal-central N2 component was enhanced by response-locked averaging in SRT, while it did not show effects of locking in DRT. The P3 component peaked at about 350ms over central sites in SRT, and at about 500ms over parietal sites in DRT; in both cases its amplitude was larger in response- than in stimulus-locked averaging. Overall, the amplitude of the preparatory components was independent from locking, the exogenous components were enhanced by stimulus locking, and the late components were more related to the response than to the stimulus. Concluding, to investigate action preparation, perception, and perceptual-decisional activity ERP studies should adopt stimulus-locked averaging with an appropriate baseline and longer pre-stimulus interval, or use both types of locking.

A novel workflow for computer guided implant surgery matching digital dental casts and CBCT scan.

Nowadays computer-guided "flap-less" surgery for implant placement using stereolithographic tem-plates is gaining popularity among clinicians and patients. The advantages of this surgical protocol are its minimally invasive nature, accuracy of implant placement, predictability, less post-surgical discomfort and reduced time required for definitive rehabilitation. Aim of this work is to describe a new protocol (Smart Fusion by Nobel Biocare), thanks to which is now possible to do a mini-invasive static guided implant surgery, in partially edentulous patients with at least 6 remaining teeth, without the use of a radiographic guide. This is possible thanks to a procedure named surface mapping based on the matching between numerous points on the surface of patient's dental casts and the corresponding anatomical surface points in the CBCT data. The full protocol is examined focusing the attention on the clinical and laboratory procedures. CONCLUSIONS: Also with some critical points and needing an adequate learning curve, this protocol allows to select the ideal implant position in depth, inclination and mesio-distal distance between natural teeth and or other implants enabling a very safe and predictable rehabilitation compared with conventional surgery. It represents a good tool for the best compromise between anatomy, function and aesthetic, able to guarantee better results in all clinical situations.

Effect of target probability on pre-stimulus brain activity.

Studies on perceptual decision-making showed that manipulating the proportion of target and non-target stimuli affects the behavioral performance. Tasks with high frequency of targets are associated to faster response times (RTs) conjunctively to higher number of errors (reflecting a response bias characterized by speed/accuracy trade-off) when compared to conditions with low frequency of targets. Electroencephalographic studies well described modulations of post-stimulus event-related potentials as effect of the stimulus probability; in contrast, in the present study we focused on the pre-stimulus preparatory activities subtending the response bias. Two versions of a Go/No-go task characterized by different proportion of Go stimuli (88% vs. 12%) were adopted. In the task with frequent go trials, we observed a strong enhancement in the motor preparation as indexed by the Bereitschaftspotential (BP, previously associated with activity within the supplementary motor area), faster RTs, and larger commission error rate than in the task with rare go trials. Contemporarily with the BP, a right lateralized prefrontal negativity (lateral pN, previously associated with activity within the dorsolateral prefrontal cortex) was larger in the task with rare go trial. In the post-stimulus processing stage, we confirmed that the N2 and the P3 components were larger for rare trials, irrespective of the Go/No-go stimulus category. The increase of activities recorded in the preparatory phase related to frequency of targets is consistent with the view proposed in accumulation models of perceptual decision for which target frequency affects the subjective baseline, reducing the distance between the starting-point and the response boundary, which determines the response speed.