Distinguishing intentional from nonintentional actions through eeg and kinematic markers.

How can an intentional movement be distinguished from the same movement done nonintentionally? How can this distinction be drawn without asking the subject, or in patients who are unable to communicate? Here we address these questions, by focusing on blinking. This is one of the most frequent spontaneous actions in our daily life, but it can also be done intentionally. Furthermore, blinking is often spared in patients with severe brain injuries, and for some, it is the only way to report complex meanings. Using kinematic and EEG-based measures, we found that intentional and spontaneous blinking are preceded by different brain activities, even when they are indistinguishable. Unlike spontaneous ones, intentional blinks are characterized by a slow negative EEG drift, resembling the classic readiness potential. We investigated the theoretical implication of this finding in stochastic decision models as well as the practical significance of using brain-based signals to improve the discrimination between intentional and nonintentional actions. As proof of principle, we considered three brain-injured patients with rare neurological syndromes characterized by motor and communicative impairments. Although further research is needed, our results indicate that brain-based signals can offer a feasible way to infer intentionality even in absence of overt communication.

PerBrain: a multimodal approach to personalized tracking of evolving state-of-consciousness in brain-injured patients: protocol of an international, multicentric, observational study.

BACKGROUND: Disorders of consciousness (DoC) are severe neurological conditions in which consciousness is impaired to various degrees. They are caused by injury or malfunction of neural systems regulating arousal and awareness. Over the last decades, major efforts in improving and individualizing diagnostic and prognostic accuracy for patients affected by DoC have been made, mainly focusing on introducing multimodal assessments to complement behavioral examination. The present EU-funded multicentric research project "PerBrain" is aimed at developing an individualized diagnostic hierarchical pathway guided by both behavior and multimodal neurodiagnostics for DoC patients. METHODS: In this project, each enrolled patient undergoes repetitive behavioral, clinical, and neurodiagnostic assessments according to a patient-tailored multi-layer workflow. Multimodal diagnostic acquisitions using state-of-the-art techniques at different stages of the patients' clinical evolution are performed. The techniques applied comprise well-established behavioral scales, innovative neurophysiological techniques (such as quantitative electroencephalography and transcranial magnetic stimulation combined with electroencephalography), structural and resting-state functional magnetic resonance imaging, and measurements of physiological activity (i.e. nasal airflow respiration). In addition, the well-being and treatment decision attitudes of patients' informal caregivers (primarily family members) are investigated. Patient and caregiver assessments are performed at multiple time points within one year after acquired brain injury, starting at the acute disease phase. DISCUSSION: Accurate classification and outcome prediction of DoC are of crucial importance for affected patients as well as their caregivers, as individual rehabilitation strategies and treatment decisions are critically dependent on the latter. The PerBrain project aims at optimizing individual DoC diagnosis and accuracy of outcome prediction by integrating data from the suggested multimodal examination methods into a personalized hierarchical diagnosis and prognosis procedure. Using the parallel tracking of both patients' neurological status and their caregivers' mental situation, well-being, and treatment decision attitudes from the acute to the chronic phase of the disease and across different countries, this project aims at significantly contributing to the current clinical routine of DoC patients and their family members. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04798456 . Registered 15 March 2021 - Retrospectively registered.

Brain plasticity after rehabilitation in a severe case of artery of Percheron stroke assessed with multimodal MR imaging.

Artery of Percheron (AOP) stroke is a rare event. We describe an AOP stroke involving both thalami and the midbrain, resulting in a multifunctional clinical impairment. Intensive inpatient multidisciplinary rehabilitation favored the recovery of motor deficits, together with the improvement of cognitive dysfunctions. MRI assessment in the chronic post-stroke phase showed structural and functional reorganization in response to the extended thalamic tissue damage and absence of revascularization. Thalamo-cortical networks involving frontal and prefrontal regions, as well as parietal areas were disrupted, whereas increased functional thalamo-occipital connectivity was found. This report sheds light on brain reorganization following AOP stroke after rehabilitation..

The role of the Sapienza GLObal Bedside Evaluation of Swallowing after Stroke (GLOBE-3S) in the prevention of stroke-associated pneumonia (SAP).

BACKGROUND AND PURPOSE: Stroke-associated pneumonia (SAP) affects 10 to 38% of patients in the acute phase of stroke. Stroke patients diagnosed with dysphagia have an 11-fold higher risk of developing SAP. Thus, identifying dysphagic patients through a highly accurate screening tool might be crucial in reducing the incidence of SAP. We present a case-control study designed to evaluate efficacy in reducing the risk of SAP between two swallowing screening tools, the classic water swallow test (WST) and a recently validated tool such as the GLOBE-3S (the Sapienza GLObal Bedside Evaluation of Swallowing after Stroke), which is a highly sensitive swallowing screening tool particularly accurate in detecting silent aspiration as well. METHODS: We analyzed the occurrence of dysphagia in 100 acute stroke patients distributed in two groups: half were screened with WST and the other half with GLOBE-3S. RESULTS: Dysphagia was diagnosed in 28 patients. The main result is that, among patients who passed the dysphagia screenings, none of those screened with the GLOBE-3S method developed pneumonia compared to 31.82% in the WST group. Discriminant function analysis (DFA) showed that NIH Stroke Scale (NIHSS) score and the dysphagia screening method (i.e., GLOBE-3S vs. WST) were the two main factors in the SAP's predicting model and the only significant ones per se. CONCLUSIONS: The new GLOBE-3S screening test can reduce the risk of SAP compared to WST.

Clinical and advanced neurophysiology in the prognostic and diagnostic evaluation of disorders of consciousness: review of an IFCN-endorsed expert group.

The analysis of spontaneous EEG activity and evoked potentialsis a cornerstone of the instrumental evaluation of patients with disorders of consciousness (DoC). Thepast few years have witnessed an unprecedented surge in EEG-related research applied to the prediction and detection of recovery of consciousness after severe brain injury,opening up the prospect that new concepts and tools may be available at the bedside. This paper provides a comprehensive, critical overview of bothconsolidated and investigational electrophysiological techniquesfor the prognostic and diagnostic assessment of DoC.We describe conventional clinical EEG approaches, then focus on evoked and event-related potentials, and finally we analyze the potential of novel research findings. In doing so, we (i) draw a distinction between acute, prolonged and chronic phases of DoC, (ii) attempt to relate both clinical and research findings to the underlying neuronal processes and (iii) discuss technical and conceptual caveats.The primary aim of this narrative review is to bridge the gap between standard and emerging electrophysiological measures for the detection and prediction of recovery of consciousness. The ultimate scope is to provide a reference and common ground for academic researchers active in the field of neurophysiology and clinicians engaged in intensive care unit and rehabilitation.

Sleep-like cortical OFF-periods disrupt causality and complexity in the brain of unresponsive wakefulness syndrome patients.

Unresponsive wakefulness syndrome (UWS) patients may retain intact portions of the thalamocortical system that are spontaneously active and reactive to sensory stimuli but fail to engage in complex causal interactions, resulting in loss of consciousness. Here, we show that loss of brain complexity after severe injuries is due to a pathological tendency of cortical circuits to fall into silence (OFF-period) upon receiving an input, a behavior typically observed during sleep. Spectral and phase domain analysis of EEG responses to transcranial magnetic stimulation reveals the occurrence of OFF-periods in the cortex of UWS patients (N = 16); these events never occur in healthy awake individuals (N = 20) but are similar to those detected in healthy sleeping subjects (N = 8). Crucially, OFF-periods impair local causal interactions, and prevent the build-up of global complexity in UWS. Our findings link potentially reversible local events to global brain dynamics that are relevant for pathological loss and recovery of consciousness.

Plasmid-mediated fluoroquinolone resistance determinants in Escherichia coli from community uncomplicated urinary tract infection in an area of high prevalence of quinolone resistance.

In Italy fluoroquinolones (FQs) are extensively prescribed in empirical therapy of uncomplicated urinary tract infection (UTI) despite recommendations in national guidelines and widespread antibiotic resistance in community. To survey the dissemination of plasmid-mediated quinolone resistance in a peak area of FQs consumption, E. coli strains from 154 community and 41 local hospital patients were collected; low level ciprofloxacin resistance qnrA, qnrB, qnrS, and aac(6)'-Ib-cr genes were screened by PCR and patterns of transferable resistances were determined. Clinical ciprofloxacin resistance in hospital doubled community value, while overall rates of FQ resistance genes were similar (31.6% and 27.8%). Prevalence of aac(6')-Ib-cr gene was 11% in outpatients (21%, inpatients) and risk of harbouring this variant was significantly associated with gentamicin resistance; linkage to ceftazidime resistance was significant (P=0.001) and six out of eight strains produced CTX-M-15 and TEM-1 beta lactamases. In transconjugants, the unique pattern ampicillin/kanamycin-gentamicin/ ESBL + was associated with aac(6')-Ib-cr gene presence and with an increase of ciprofloxacin MIC value. Data highlight the need to monitor the resistance risk factors in the local community to provide clinicians with well-grounded guidelines for UTI therapy.

pUB2380: characterization of a ColD-like resistance plasmid.

A detailed analysis of the mobilizable, ColE1-like resistance plasmid, pUB2380, is reported. The 8.5-kb genome encodes six (possibly seven) major functions: (1) a ColD-like origin of replication, oriV, with associated replication functions, RNAI and RNAII; (2) a set of active mobilization functions highly homologous to that of ColE1, including the origin of transfer, oriT; (3) a ColE1-like multimer resolution site (cer); (4) a kanamycin-resistance determinant, aph, encoding an aminoglycoside-3'-phosphotransferase type 1; (5) an insertion sequence, IS1294; and (6) two genes, probably cotranscribed, of unknown function(s). The GC content of the various parts of the genome indicates that the plasmid is a hybrid structure assembled from DNA from at least three different sources, of which the replication region, the mobilization functions, and the resistance gene are likely to have originated in the enterobacteriaceae.

IS1294, a DNA element that transposes by RC transposition.

IS1294, found on the ColD-like resistance plasmid pUB2380, is IS91-like. It is an active 1.7-kb insertion sequence that lacks terminal inverted repeats, displays insertion-site specificity, and does not generate direct repeats of the target site. The element has one large open reading frame, tnp(1294), encoding a transposase of 351 amino acids, related to members of the REP family of replication proteins used by RC-plasmids of gram-positive bacteria. IS1294 transposes using rolling-circle replication, initiated at one end of the element, oriIS, and terminated at the other, terIS. oriIS and terIS are highly conserved among like IS elements. oriIS resembles the leading strand replication origins of RC-plasmids; terIS resembles a rho-independent transcription terminator. IS1294 mediates not only its own transposition, but also sequences adjacent to terIS. A transposition model for IS1294 and related elements, involving rolling-circle replication and single-strand DNA intermediates, is presented.

Diagnostic value of anti-hepatitis C virus (HCV) core immunoglobulin M in recurrence of HCV infection after orthotopic liver transplantation.

The significance of anti-hepatitis C virus (HCV) core immunoglobulin M (IgM) and its relationship with genotypes, alanine aminotransferase abnormality, and histological data were studied for 18 patients who had undergone orthotopic liver transplantation due to HCV-related end-stage disease. During follow-up, IgM response seemed to be associated with the recurrence of HCV infection but did not correlate with abnormal alanine aminotransferase levels and histological data. In addition, the results of this study indicated that the detection of HCV RNA is critical for diagnosis of reinfection in liver transplantation.

Antibacterial spectra of drugs used for chemotherapy of mycobacterial infections.

The mechanism of action of many antimycobacterial agents is poorly understood. To obtain preliminary information on whether the targets for some of these drugs might also occur in other bacteria, the in vitro activities of selected agents against Escherichia coli, Bacillus subtilis and Staphylococcus aureus were determined. Dapsone, p-aminosalicylic acid and thiacetazone failed to inhibit the above organisms (MIC values > 100 micrograms/ml) that may therefore lack targets for these drugs. Capreomycin, viomycin and clofazimine demonstrated activity against some of the organisms (MIC values < 100 micrograms/ml) suggesting that the targets of these drugs may not be restricted to mycobacterial species. The agents were all potent inhibitors of Mycobacterium bovis bacille Calmette-Guérin (MIC values 0.08-0.5 microgram/ml).

Evolution of R plasmids by replicon fusion.

The occurrence of plasmid-plasmid fusions in nature and their possible influence on the spread of bacterial drug resistance is considered. Three ways in which replicon fusions can be formed are described; specifically fusions mediated by IS elements, "one-ended transposition" systems derived from Tn3 and like transposons, and pUB2380, a prototype for a new type of transposition. Non-transposition based systems which mediate replicon fusion are also briefly considered.

Stability of plasmid content in Salmonella wien in late phases of the epidemic history.

Prevalence, genetic characteristics, and EcoRI cleavage analysis of plasmids identified in clinical strains of Salmonella wien isolated in recent years showed that the plasmid content in this serotype has remained uniform and stable over more than a decade and also late in the epidemic history. No correlation between decrease in S. wien isolations and naturally occurring systematic changes in the DNA of its most common FIme plasmid was structurally detectable.

[In vitro and in vivo antibacterial activity of cephapirin-dicloxacillin combination in the ratio 1:1]. / Attivta' antibetterica "in vivo dell'associazione cefapi-rine - dicloxacillina in rapporto 1:1.

Studies were carried out on the combination, 1:1 ratio, of two antibiotics: cephapirin and dicloxacillin. After the analysis of the activity spectrum "in vitro" of each antibiotics, the synergism of this combination against the Gram-negative bacteria strains was clearly demonstrated. This combination demonstrated a particular activity against the beta-lactamases producing strains "in vitro" as well in protection tests "in vivo" in experimental infections in mice.