Low testosterone predicts hypoxemic respiratory insufficiency and mortality in patients with COVID-19 disease: another piece in the COVID puzzle.

PURPOSE: Hypogonadism was described in high number of male subjects with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we investigated whether low testosterone (T) values may influence the clinical presentation and outcome of SARS-CoV-2-related pneumonia in a large population of adult males with coronavirus disease 19 (COVID-19). METHODS: Two hundred twenty one adult males hospitalized for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano-Milan (Italy) were consecutively evaluated for arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, serum T and inflammatory parameters at study entry, need of ventilation during hospital stay and in-hospital mortality. RESULTS: Subjects low T values (< 8 nmol/L; 176 cases) were significantly older (P = 0.001) and had higher serum interleukin-6 (P = 0.001), C-reactive protein (P < 0.001), lactate dehydrogenase (P < 0.001), ferritin (P = 0.012), lower P/F ratio (P = 0.001), increased prevalence of low T3 syndrome (P = 0.041), acute respiratory insufficiency (P < 0.001), more frequently need of ventilation (P < 0.001) and higher mortality rate (P = 0.009) compared to subjects with higher T values. In the multivariable regression analyses, T values maintained significant associations with acute respiratory insufficiency (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.79-0.94; P < 0.001 and in-hospital mortality (OR 0.80, 95% CI 0.69-0.95; P = 0.009), independently of age, comorbidities, thyroid function and inflammation. CONCLUSION: Low T levels values are associated with unfavorable outcome of COVID-19. Prospective studies are needed to evaluate the long-term outcomes of hypogonadism related to COVID-19 and the clinical impact of T replacement during and after acute illness.

Vitamin D deficiency, secondary hyperparathyroidism and respiratory insufficiency in hospitalized patients with COVID-19.

PURPOSE: Hypovitaminosis D has emerged as potential risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the general population with variable effects on the outcome of the coronavirus disease-19 (COVID-19). The aim of this retrospective single-center study was to investigate the impact of hypovitaminosis D and secondary hyperparathyroidism on respiratory outcomes of COVID-19. METHODS: Three-hundred-forty-eight consecutive patients hospitalized for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano, Milan (Italy) were evaluated for arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, serum 25hydroxy-vitamin D [25(OH)D], parathyroid hormone (PTH) and inflammatory parameters at study entry and need of ventilation during the hospital stay. RESULTS: In the entire population, vitamin D deficiency (i.e., 25(OH)D values < 12 ng/mL) was significantly associated with acute hypoxemic respiratory failure at the study entry [adjusted odds ratio (OR) 2.48, 95% confidence interval 1.29-4.74; P = 0.006], independently of age and sex of subjects, serum calcium and inflammatory parameters. In patients evaluated for serum PTH (97 cases), secondary hyperparathyroidism combined with vitamin D deficiency was significantly associated with acute hypoxemic respiratory failure at study entry (P = 0.001) and need of ventilation during the hospital stay (P = 0.031). CONCLUSION: This study provides evidence that vitamin D deficiency, when associated with secondary hyperparathyroidism, may negatively impact the clinical outcome of SARS-CoV-2-related pneumonia.

No evidence of increased cerebrovascular involvement in adult neurologically-asymptomatic ß-Thalassaemia. A multicentre multimodal magnetic resonance study.

Multi-factorial causes jeopardize brain integrity in ß-thalassaemia. Intracranial parenchymal and vascular changes have been reported among young ß-thalassaemia patients but conventional magnetic resonance imaging (MRI) findings are contradictory making early MRI and magnetic resonance angiography (MRA)/venography monitoring a matter of debate. This study prospectively investigated 75 neurologically asymptomatic ß-thalassaemia patients (mean-age 35·2 ± 10·7 years; 52/75 transfusion-dependent; 41/75 splenectomised) using a 3T magnetic resonance scanner; clinical, laboratory and treatment data were also collected. White matter ischaemic-like abnormalities, intracranial artery stenoses, aneurysms and sinus venous thrombosis were compared between patients and 56 healthy controls (mean-age 33·9 ± 10·8 years). No patient or control showed silent territorial or lacunar strokes, intracranial artery stenoses or signs of sinus thrombosis. White matter lesions were found both in patients (35/75, 46·7%) and controls (28/56, 50·0%), without differences in terms of number (4·0 ± 10·6 vs. 4·6 ± 9·1, P = 0·63), size and Fazekas' Score. Intracranial aneurysms did not differ between patients and controls for incidence rate (7/75, 9·3% vs. 5/56, 8·9%), size and site. Vascular and parenchymal abnormality rate did not differ according to treatments or clinical phenotype. According to this study, asymptomatic ß-thalassaemia patients treated according to current guidelines do not seem to carry an increased risk of brain and intracranial vascular changes, thus weakening recommendations for regular brain MRI monitoring.

The impact of different 18FDG PET healthy subject scans for comparison with single patient in SPM analysis.

BACKGROUND: Statistical Parametric Mapping (SPM) has been applied for single-subject evaluation of [18F]FDG uptake in Alzheimer Disease (AD). In a single-subject framework, the patient is compared to a dataset of [18F]FDG PET images from healthy subjects (HS) evaluating brain metabolic abnormalities. No studies exist that assess the effects on SPM analysis of HS [18F]FDG PET datasets acquired from different subjects and using different PET scanners including the same or different PET scanners than those used for patients. This work aims to elucidate this issue from a methodological perspective. METHODS: We considered six different [18F]FDG PET datasets, from different HS populations, acquired by different PET scanners. We applied SPM5 procedures for single-subject comparison with each of the six HS datasets in 10 probable AD patients showing the typical [18F]FDG pattern. We also implemented the same comparison in 3 probable AD patients and in 7 patients with a clinical diagnosis of Mild Cognitive Impariment (MCI), showing subtle changes on visual inspection of [18F]FDG distribution. RESULTS: Considering the 10 patients with the typical [18F]FDG pattern, the results were comparable for all the SPM maps. In the 3 probable AD patients with subtle changes in [18F]FDG distribution, no significant AD pattern emerged when a small number (<20) of HS was used, whereas a significant AD pattern appeared when a large (>50) HS image set was used. In the 7 considered MCI patients the use of a large (>50) HS image set allowed to assess significant hypometabolic patterns related to a probable neurodegenerative pathology. CONCLUSIONS: The use of large HS datasets of PET scans (>50) is recommended for single-subject SPM analysis. On condition that appropriate preprocessing steps are provided, large HS datasets can include HS images acquired with different PET systems, not including images from the same scanner of that used for patients.

Language Control in Bilinguals: Monitoring and Response Selection.

Language control refers to the cognitive mechanism that allows bilinguals to correctly speak in one language avoiding interference from the nontarget language. Bilinguals achieve this feat by engaging brain areas closely related to cognitive control. However, 2 questions still await resolution: whether this network is differently engaged when controlling nonlinguistic representations, and whether this network is differently engaged when control is exerted upon a restricted set of lexical representations that were previously used (i.e., local control) as opposed to control of the entire language system (i.e., global control). In the present event-related functional magnetic resonance imaging study, we investigated these 2 questions by employing linguistic and nonlinguistic blocked switching tasks in the same bilingual participants. We first report that the left prefrontal cortex is driven similarly for control of linguistic and nonlinguistic representations, suggesting its domain-general role in the implementation of response selection. Second, we propose that language control in bilinguals is hierarchically organized with the dorsal anterior cingulate cortex/presupplementary motor area acting as the supervisory attentional system, recruited for increased monitoring demands such as local control in the second language. On the other hand, prefrontal, inferior parietal areas and the caudate would act as the response selection system, tailored for language selection for both local and global control.

The effectiveness of domestic cook on inactivation of murine norovirus in experimentally infected Manila clams (Ruditapes philippinarum).

AIM: The aim of this work was to evaluate the efficacy of domestic cooking in inactivating Manila clams experimentally infected with murine norovirus (MNV). METHODS AND RESULTS: A cooking pan was modified to enable electronic temperature probes to be positioned to record both flesh and environment temperature. Manila clams were infected with 10(4) TCID 50% ml(-1) of MNV. The infected whole-in-shell clams, divided into three replicates, were cooked on an electric stove, and groups of nine clams were removed from the pan at fixed intervals. Pools of three digestive glands were examined by virus isolation to ascertain residual viral load. CONCLUSION: Results showed that 10 min of cooking by a traditional domestic method at a temperature close to 100°C, for at least 2 min, can completely devitalize the MNV in infected clams. This is generally the time needed for the majority of valves to open up. SIGNIFICANCE AND IMPACT OF THE STUDY: At present, it is highly recommended to label all lagoon products as 'requiring cooking before consumption', but no specifications are given on how long and at what temperature they should be cooked. Our results can provide the consumer with useful indications on how to cook clams to prevent any risk of foodborne illness.

The maternal-fetal neurodevelopmental groundings of preterm birth risk.

Background: Altered neurodevelopment is a major clinical sequela of Preterm Birth (PTB) being currently unexplored in-utero. Aims: To study the link between fetal brain functional (FbF) connectivity and preterm birth, using resting-state functional magnetic resonance imaging (rs-fMRI). Study design: Prospective single-centre cohort study. Subjects: A sample of 31 singleton pregnancies at 28-34 weeks assigned to a low PTB risk (LR) (n = 19) or high PTB risk (HR) (n = 12) group based on a) the Maternal Frailty Inventory (MaFra) for PTB risk; b) a case-specific PTB risk gradient. Methods: Fetal brain rs-fMRI was performed on 1.5T MRI scanner. First, directed causal relations representing fetal brain functional connectivity measurements were estimated using the Greedy Equivalence Search (GES) algorithm. HR vs. LR group differences were then tested with a novel ad-hoc developed Monte Carlo permutation test. Second, a MaFra-only random forest (RF) was compared against a MaFra-Neuro RF, trained by including also the most important fetal brain functional connections. Third, correlation and regression analyses were performed between MaFra-Neuro class probabilities and i) the GA at birth; ii) PTB risk gradient, iii) perinatal clinical conditions and iv) PTB below 37 weeks. Results: First, fewer fetal brain functional connections were evident in the HR group. Second, the MaFra-Neuro RF improved PTB risk prediction. Third, MaFra-Neuro class probabilities showed a significant association with: i) GA at birth; ii) PTB risk gradient, iii) perinatal clinical conditions and iv) PTB below 37 weeks. Conclusion: Fetal brain functional connectivity is a novel promising predictor of PTB, linked to maternal risk profiles, ahead of birth, and clinical markers of neurodevelopmental risk, at birth, thus potentially "connecting" different PTB phenotypes.

Completion surgery after concomitant chemoradiation in obese women with locally advanced cervical cancer: Evaluation of toxicity and outcome measures.

BACKGROUND: This study aims at comparing the morbidity and oncologic outcomes in normal weight, overweight, and obese women with locally advanced cervical cancers (LACC) submitted to radical surgery after chemoradiation. METHODS: A review of LACC patients with body mass index (BMI) ≥ 18.5 kg/m(2) who underwent neoadjuvant chemoradiation followed by radical surgery between January 1996 and December 2010 was performed. BMI categories were created according to the World Health Organization (WHO) classification. RESULTS: Two hundred sixty-eight women met the inclusion criteria: 118 (44.0%) were normal weight, 100 (37.3%) overweight and 50 (18.7%) obese. The median follow-up was 42 months. Higher BMI was associated with older age (p = 0.0041), while there were no differences among the three groups in Charlson comorbidity score, tumor characteristics, radiotherapy dosing, type of surgery, and pathological response. There were no differences among the three groups in the intraoperative and postoperative complications as well as rate of patients requiring adjuvant treatments: 21 (7.8%) patients experienced grade 3-4 toxicity, including six normal weight, 12 overweight and three obese patients (p = 0.14). Only the rate of grade 1-2 skin toxicity was higher in obese (14%) with respect to overweight (1%) and normal women (0%) (p = 0.00001). There were no differences in the five-year DFS (74%, 77%, and 84% for normal weight, overweight, and obese women, respectively, p = n.s.), and five-year OS (76%, 78%, and 78% for normal weight, overweight, and obese women, respectively, p = n.s.). CONCLUSIONS: The role of obesity should not be overestimated when evaluating the chance of enrolment of LACC patients into preoperative chemoradiation protocols.

An Italian battery for the assessment of semantic memory disorders.

We report the construction and standardization of a new comprehensive battery of tests for the assessment of semantic memory disorders. The battery is constructed on a common set of 48 stimuli, belonging to both living and non-living categories, rigidly controlled for several confounding variables, and is based on an empirically derived corpus of semantic features. It includes six tasks, in order to assess semantic memory through different modalities of input and output: two naming tasks, one with colored pictures and the other in response to an oral description, a word-picture matching task, a picture sorting task, a free generation of features task and a sentence verification task. Normative data on 106 Italian subjects pooled across homogenous subgroups for age, sex and education are reported. The new battery allows an in-depth investigation of category-specific disorders and of progressive semantic memory deficits at features level, overcoming some of the limitations of existing tests.

To bridge or not to bridge: Moral Judgement in Cocaine Use Disorders, a case-control study on human morality.

BACKGROUND: In the "Dual-Process theory", morality is characterized by the interaction between an automatic-emotional process, mediated by the Anterior Cingulate Cortex (ACC) and linked to personal-deontological decisions, and a rational-conscious one, mediated by the Dorso-Lateral Prefrontal Cortex (DLPFC) and linked to impersonal-utilitarian decisions. These areas are altered by chronic use of cocaine, with a possible impact on moral decision-making. OBJECTIVE: To evaluate the difference between a group of Cocaine Use Disorder (CUD) patients and a control group in moral decision-making. METHODS: Subjects with CUD were compared to an equal-sized healthy group regarding their moral decision-making. Trolley and Footbridge Moral Dilemmas were administered to each group. The quality of the answer (yes or no) and the time needed to answer were recorded. RESULTS: The recruited group includes 72 subjects, 36 with CUD and 36 healthy subjects (average age of 39.51 ± 9.89). In the Trolley dilemma, almost all the subjects (97.3%) answered "yes", while in the Footbridge dilemma CUD subjects answered "yes" more often (52.7%) than the healthy group (19.4%). CONCLUSION: For strong emotional dilemmas (Footbridge), cocaine users answered "yes" with a higher frequency compared to healthy subjects, highlighting a wider utilitarian tendency in decision-making and a poor emotional participation.

Targeting Cytotoxic Agents through EGFR-Mediated Covalent Binding and Release.

A major drawback of cytotoxic chemotherapy is the lack of selectivity toward noncancerous cells. The targeted delivery of cytotoxic drugs to tumor cells is a longstanding goal in cancer research. We proposed that covalent inhibitors could be adapted to deliver cytotoxic agents, conjugated to the ß-position of the Michael acceptor, via an addition-elimination mechanism promoted by covalent binding. Studies on model systems showed that conjugated 5-fluorouracil (5FU) could be released upon thiol addition in relevant time scales. A series of covalent epidermal growth factor receptor (EGFR) inhibitors were synthesized as their 5FU derivatives. Achieving the desired release of 5FU was demonstrated to depend on the electronics and geometry of the compounds. Mass spectrometry and NMR studies demonstrated an anilinoquinazoline acrylate ester conjugate bound to EGFR with the release of 5FU. This work establishes that acrylates can be used to release conjugated molecules upon covalent binding to proteins and could be used to develop targeted therapeutics.

Contribution of ultrasound in the assessment of nerve diseases.

BACKGROUND AND PURPOSE: Recently, ultrasound (US) has been used to assess the peripheral nervous system; however, there is no real study about its possible significant role in routine practice. Our study aims to assess the contribution of US as a routine tool in a neurophysiological laboratory. METHODS: The study assesses 130 patients who presented clinical suspicion of peripheral nerve diseases, excluding motor neuron disease, radiculopathy, hereditary and acquired polyneuropathy. All patients were clinically, neurophysiologically and sonographically assessed in the same session by the same neurologist/neurophysiologist. To avoid interpretation bias, two independent and blinded clinicians, different than the examiners performing electrodiagnosis and US, reviewed clinical, neurophysiological and US findings (also data about follow-up, when available) and classified the contribution of US as follows: Contributive (US had influence on the diagnostic and therapeutic strategies), Confirming (US confirmed the clinical and neurophysiological diagnosis), Non-Confirming (US findings were normal) and Incorrect (US findings led to incorrect diagnosis). RESULTS: US impacted, namely modified the diagnostic and therapeutic path in 42.3% of cases (55 patients); US had a confirmatory role in 40% (52 patients); US did not confirm clinical and neurophysiological diagnosis in 17.7% (23 cases); no incorrect US findings were observed. CONCLUSION: US complements neurophysiological assessment even in routine practice, and this confirms the increasing interest in US for a multidimensional evaluation of peripheral nerve system diseases.

Monitoring AMR in Campylobacter jejuni from Italy in the last 10 years (2011-2021): Microbiological and WGS data risk assessment.

Campylobacter jejuni is considered as the main pathogen in human food-borne outbreaks worldwide. Over the past years, several studies have reported antimicrobial resistance (AMR) in C. jejuni strains. In Europe, the official monitoring of AMR comprises the testing of Campylobacter spp. from food-producing animals because this microorganism is responsible for human infections and usually predominant in poultry. Food-producing animals are considered to be a major source of campylobacteriosis through contamination of food products. Concerns are growing due to the current classification of C. jejuni by the WHO as a 'high priority pathogen' due to the emergence of resistance to multiple drugs such as those belonging to the fluoroquinolones, macrolides and other classes, which limits the treatment alternatives. Knowledge about the contributions of different food sources to gastrointestinal disease is fundamental to prioritise food safety interventions and to establish proper control strategies. Assessing the genetic diversity among Campylobacter species is essential to the understanding of their epidemiology and population structure. Using a population genetic approach and grouping the isolates into sequence types within different clonal complexes, it is possible to investigate the source of the human cases. The work programme was aimed for the fellow to assess the AMR of C. jejuni isolated from humans, poultry and birds from wild and urban Italian habitats. Given the public health concern represented by resistant pathogens in food-producing animals and the paucity of data about this topic in Italy, the aim was to identify correlations between phenotypic and genotypic AMR and comparing the origin of the isolates. The work programme allowed the fellow to acquire knowledge, skills and competencies on the web-based tools used by IZSAM to process the NGS data and perform bioinformatics analyses for the identification of epidemiological clusters, the study of AMR patterns in C. jejuni isolates, and the assessment of the human exposure to such AMR pathogens. Furthermore, the fellow became able to transfer the acquired knowledge through innovative web-based didactical tools applied to WGS and clustering of specific food-borne pathogens, with particular reference to C. jejuni. To achieve this objective, 2,734 C. jejuni strains isolated from domestic and wild animals and humans, during the period 2011-2021 were analysed. The resistance phenotypes of the isolates were determined using the microdilution method with EUCAST breakpoints, for the following antibiotics: nalidixic acid, ciprofloxacin, chloramphenicol, erythromycin, gentamicin, streptomycin, tetracycline. The data were complemented by WGS data for each strain, uploaded in the Italian information system for the collection and analysis of complete genome sequence of pathogens isolated from animal, food and environment (GENPAT) developed and maintained at IZSAM; information like clonal complex and sequence type to understand the phylogenetical distance between strains according to their origins were also considered. This work underlines that a better knowledge of the resistance levels of C. jejuni is necessary, and mandatory monitoring of Campylobacter species in the different animal productions is strongly suggested.

Acquired myasthenia gravis with concurrent polymyositis and myocarditis secondary to a thymoma in a dog.

Background: Canine thymomas are associated with multiple paraneoplastic syndromes, among which myasthenia gravis (MG) is the most common. Acquired MG is an autoimmune disease characterized by the presence of antibodies against acetylcholine receptors (ACHRs). ACHRs antibodies are the most commonly formed, but the production of antistriational antibodies binding to skeletal and cardiac muscle proteins has also been recorded both in humans and dogs. An association between the occurrence of antistriational antibodies and a severe form of myocarditis, giant cell myocarditis, has been described in humans. Case Description: A 4-year-old mixed-breed dog was referred because of 1 month history of exercise-induced weakness, hypersalivation, and regurgitation. The neurologic examination was indicative of a neuromuscular junction disease, and MG was suspected. A computed tomographic scan examination showed the presence of a megaoesophagus and a thymic mass. Serum antibodies against ACHRs confirmed the diagnosis of MG. Treatment with pyridostigmine was started, and the thymic mass was surgically excised, and a diagnosis of thymoma was confirmed by histology. 24 hours after surgery, the dog developed a third-degree atrioventricular block. Severe arrhythmia and increased troponin serum levels suggested myocarditis which rapidly led to cardiopulmonary arrest. Histopathologic examination of the heart, esophagus and diaphragm revealed a lymphocytic and macrophagic infiltration, consistent with myocarditis and polymyositis. Scattered rare giant multinucleated cells were also detected in the myocardium. Conclusion: To the author's knowledge, this is the first report of thymoma-associated MG with concurrent polymyositis and giant cell-like myocarditis in a dog.

Beyond the abstract-concrete dichotomy: mode of acquisition, concreteness, imageability, familiarity, age of acquisition, context availability, and abstractness norms for a set of 417 Italian words.

The main objective of this study is to investigate the abstract-concrete dichotomy by introducing a new variable: the mode of acquisition (MoA) of a concept. MoA refers to the way in which concepts are acquired: through experience, through language, or through both. We asked 250 participants to rate 417 words on seven dimensions: age of acquisition, concreteness, familiarity, context availability, imageability, abstractness, and MoA. The data were analyzed by considering MoA ratings and their relationship with the other psycholinguistic variables. Distributions for concreteness, abstractness, and MoA ratings indicate that they are qualitatively different. A partial correlation analysis revealed that MoA is an independent predictor of concreteness or abstractness, and a hierarchical multiple regression analysis confirmed MoA as being a valid predictor of abstractness. Strong correlations with measures for the English translation equivalents in the MRC database confirmed the reliability of our norms. The full database of MoA ratings and other psycholinguistic variables may be downloaded from http://brm.psychonomic-journals.org/content/supplemental or www.abstract-project.eu.

Postoperative treatment with phytotheraphy Graminex G63 (CERNILEN-Flogo®) after greenlight laser XPS (180W) photovaporization of the prostate (PVP), can affect patient's quality of life?

OBJECTIVE: Phytotherapic treatment as Cernilen-flogo® is commonly used to treat chronic pelvic pain, chronic prostatitis, and BPE (benign prostatic enlargement). In our study, for the first time, we aim to evaluate postoperatively Cernilen-flogo® therapy in patients with BPE/LUTS (lower urinary tract symptoms) previously treated with Greenlight laser XPS (180W) photovaporization of prostate (PVP) to improve surgical outcomes. MATERIALS AND METHODS: We collected data from patients treated with PVP for BPE/LUTS international prostate symptom score (IPSS) >20 unresponding to conventional treatment. Two groups of patients were analyzed: Group A including 15 patients (50%) treated postoperatively with Cernilen-flogo® vs. no treatment Group B. One expert surgeon performed all the procedures. RESULTS: 30 patients included with BPE/LUTs previously treated with PVP. There was no difference between patients' demographic, median age, prostate volume and PSA (prostate specific antigen) level. All patients had a postoperative evaluation after 30-45 days. Patients with postoperative complications (acute urinary retention, postoperative hematuria) were excluded from our study. All patients had a preoperative and postoperative evaluation of IPSS, bother score (BS) and pelvic discomfort (visual analogic scale VAS). Preoperatively there was no significative difference in IPSS, BS and VAS. IPSS Group A was postoperatively 7.13 (SD 1.64) and Group B was 7.33 (SD 1.58) (p=0.67); BS Group A was postoperatively 1.33 (SD 0.81), Group B was 1.73 (SD 1.09) (p=0.30), and VAS Group A was 2.73 (SD 1.9) and Group B was 4.33 (SD 1.58) (p=0.004) showing a statistically significative difference between the two groups in pelvic discomfort with a better outcome in patients treated with Cernilen-flogo®. CONCLUSIONS: Our study showed that Cernilen-flogo® treatment after PVP is effective and minimize patient's pelvic discomfort showed by lower VAS level resulting in better postoperatively patient's quality of life (QOL).

Subcortico-Cortical Functional Connectivity in the Fetal Brain: A Cognitive Development Blueprint.

Recent evidence has shown that patterns of cortico-cortical functional synchronization are consistently traceable by the end of the third trimester of pregnancy. The involvement of subcortical structures in early functional and cognitive development has never been explicitly investigated, notwithstanding their pivotal role in different cognitive processes. We address this issue by exploring subcortico-cortical functional connectivity at rest in a group of normally developing fetuses between the 25th and 32nd weeks of gestation. Results show significant functional coupling between subcortical nuclei and cortical networks related to: (i) sensorimotor processing, (ii) decision making, and (iii) learning capabilities. This functional maturation framework unearths a Cognitive Development Blueprint, according to which grounding cognitive skills are planned to develop with higher ontogenetic priority. Specifically, our evidence suggests that a newborn already possesses the ability to: (i) perceive the world and interact with it, (ii) create salient representations for the selection of adaptive behaviors, and (iii) store, retrieve, and evaluate the outcomes of interactions, in order to gradually improve adaptation to the extrauterine environment.

Development of food safety risk assessment tools based on molecular typing and WGS of Campylobacter jejuni genome.

The 'learning-by-doing' EU-FORA fellowship programme in the development of risk assessment tools based on molecular typing and WGS of Campylobacter jejuni genome was structured into two main activities: the primary one focused on training on risk assessment methodology and the secondary one in starting and enhancing the cooperation between the hosting and home organisations, or other joint activities. The primary activities had three subsequent work packages (WPs): WP1 data organisation, WP2 cluster and association analyses, and WP3 development of risk assessment models. The secondary activities have branched into one workshop and the initiation of a cooperation programme between the hosting and home organisations. In the last quarter, the fellow had contributed to the characterisation of some pathogens in possible response to a changing climate, part of the CLEFSA project. The fellow attended various forms of training: online and on-site courses, and also participated at several conferences and meetings for improving his knowledge and skills, contributing to performing the Campylobacter risk assessment and source attribution.

Negation in the brain: modulating action representations.

Sentential negation is a universal syntactic feature of human languages that reverses the truth value expressed by a sentence. An intriguing question concerns what brain mechanisms underlie our ability to represent and understand the meaning of negative sentences. We approach this issue by investigating action-related language processing and the associated neural representations. Using functional magnetic resonance imaging we measured brain activity in 18 healthy subjects during passive listening of sentences characterized by a factorial combination of polarity (affirmative vs. negative) and concreteness (action-related vs. abstract). Negation deactivated cortical areas and the left pallidum. Compared to abstract sentences, action-related sentences activated the left-hemispheric action-representation system. Crucially, the polarity by concreteness interactions showed that the activity within the action-representation system was specifically reduced for negative action-related vs. affirmative action-related sentences (compared to abstract sentences). Accordingly, functional integration within this system as measured by Dynamic Causal Modeling was specifically weaker for negative action-related than for affirmative action-related sentences. This modulation of action representations indicates that sentential negation transiently reduces the access to mental representations of the negated information.

Alternating Dynamics of Segregation and Integration in Human EEG Functional Networks During Working-memory Task.

Brain functional networks show high variability in short time windows but mechanisms governing these transient dynamics remain unknown. In this work, we studied the temporal evolution of functional brain networks involved in a working memory (WM) task while recording high-density electroencephalography (EEG) in human normal subjects. We found that functional brain networks showed an initial phase characterized by an increase of the functional segregation index followed by a second phase where the functional segregation faded after the prevailing the functional integration. Notably, wrong trials were associated with different or disrupted sequences of the segregation-integration profiles and measures of network centrality and modularity were able to identify crucial aspects of the oscillatory network dynamics. Additionally, computational investigations further supported the experimental results. The brain functional organization may respond to the information processing demand of a WM task following a 2-step atomic scheme wherein segregation and integration alternately dominate the functional configurations.