4D flow imaging of the thoracic aorta: is there an added clinical value?

Four-dimensional (4D) flow MRI has emerged as a powerful non-invasive technique in cardiovascular imaging, enabling to analyse in vivo complex flow dynamics models by quantifying flow parameters and derived features. Deep knowledge of aortic flow dynamics is fundamental to better understand how abnormal flow patterns may promote or worsen vascular diseases. In the perspective of an increasingly personalized and preventive medicine, growing interest is focused on identifying those quantitative functional features which are early predictive markers of pathological evolution. The thoracic aorta and its spectrum of diseases, as the first area of application and development of 4D flow MRI and supported by an extensive experimental validation, represents the ideal model to introduce this technique into daily clinical practice. The purpose of this review is to describe the impact of 4D flow MRI in the assessment of the thoracic aorta and its most common affecting diseases, providing an overview of the actual clinical applications and describing the potential role of derived advanced hemodynamic measures in tailoring follow-up and treatment

Dopamine dysregulation syndrome in Parkinson's disease: from clinical and neuropsychological characterisation to management and long-term outcome

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Should entanglement measures be monogamous or faithful?

“Is entanglement monogamous?” asks the title of a popular article [B. Terhal, IBM J. Res. Dev. 48, 71 (2004)], celebrating C. H. Bennett’s legacy on quantum information theory. While the answer is affirmative in the qualitative sense, the situation is less clear if monogamy is intended as a quantitative limitation on the distribution of bipartite entanglement in a multipartite system, given some particular measure of entanglement. Here, we formalize what it takes for a bipartite measure of entanglement to obey a general quantitative monogamy relation on all quantum states. We then prove that an important class of entanglement measures fail to be monogamous in this general sense of the term, with monogamy violations becoming generic with increasing dimension. In particular, we show that every additive and suitably normalized entanglement measure cannot satisfy any nontrivial general monogamy relation while at the same time faithfully capturing the geometric entanglement structure of the fully antisymmetric state in arbitrary dimension. Nevertheless, monogamy of such entanglement measures can be recovered if one allows for dimension-dependent relations, as we show explicitly with relevant examples

Chest CT score in COVID-19 patients: correlation with disease severity and short-term prognosis

Objectives: To correlate a CT-based semi-quantitative score of pulmonary involvement in COVID-19 pneumonia with clinical staging of disease and laboratory findings. We also aimed to investigate whether CT findings may be predictive of patients’ outcome. Methods: From March 6 to March 22, 2020, 130 symptomatic SARS-CoV-2 patients were enrolled for this single-center analysis and chest CT examinations were retrospectively evaluated. A semi-quantitative CT score was calculated based on the extent of lobar involvement (0:0%; 1, < 5%; 2:5–25%; 3:26–50%; 4:51–75%; 5, > 75%; range 0–5; global score 0–25). Data were matched with clinical stages and laboratory findings. Survival curves and univariate and multivariate analyses were performed to evaluate the role of CT score as a predictor of patients’ outcome. Results: Ground glass opacities were predominant in early-phase (≤ 7 days since symptoms’ onset), while crazy-paving pattern, consolidation, and fibrosis characterized late-phase disease (> 7 days). CT score was significantly higher in critical and severe than in mild stage (p < 0.0001), and among late-phase than early-phase patients (p < 0.0001). CT score was significantly correlated with CRP (p < 0.0001, r = 0.6204) and D-dimer (p < 0.0001, r = 0.6625) levels. A CT score of ≥ 18 was associated with an increased mortality risk and was found to be predictive of death both in univariate (HR, 8.33; 95% CI, 3.19–21.73; p < 0.0001) and multivariate analysis (HR, 3.74; 95% CI, 1.10–12.77; p = 0.0348). Conclusions: Our preliminary data suggest the potential role of CT score for predicting the outcome of SARS-CoV-2 patients. CT score is highly correlated with laboratory findings and disease severity and might be beneficial to speed-up diagnostic workflow in symptomatic cases. Key Points: • CT score is positively correlated with age, inflammatory biomarkers, severity of clinical categories, and disease phases. • A CT score ≥ 18 has shown to be highly predictive of patient’s mortality in short-term follow-up. • Our multivariate analysis demonstrated that CT parenchymal assessment may more accurately reflect short-term outcome, providing a direct visualization of anatomic injury compared with non-specific inflammatory biomarkers

Plasma neurofilament light chain protein is not increased in treatment-resistant schizophrenia and first-degree relatives

Objective: Schizophrenia, a complex psychiatric disorder, is often associated with cognitive, neurological and neuroimaging abnormalities. The processes underlying these abnormalities, and whether a subset of people with schizophrenia have a neuroprogressive or neurodegenerative component to schizophrenia, remain largely unknown. Examining fluid biomarkers of diverse types of neuronal damage could increase our understanding of these processes, as well as potentially provide clinically useful biomarkers, for example with assisting with differentiation from progressive neurodegenerative disorders such as Alzheimer and frontotemporal dementias. Methods: This study measured plasma neurofilament light chain protein (NfL) using ultrasensitive Simoa technology, to investigate the degree of neuronal injury in a well-characterised cohort of people with treatment-resistant schizophrenia on clozapine (n = 82), compared to first-degree relatives (an at-risk group, n = 37), people with schizophrenia not treated with clozapine (n = 13), and age- and sex-matched controls (n = 59). Results: We found no differences in NfL levels between treatment-resistant schizophrenia (mean NfL, M = 6.3 pg/mL, 95% confidence interval: [5.5, 7.2]), first-degree relatives (siblings, M = 6.7 pg/mL, 95% confidence interval: [5.2, 8.2]; parents, M after adjusting for age = 6.7 pg/mL, 95% confidence interval: [4.7, 8.8]), controls (M = 5.8 pg/mL, 95% confidence interval: [5.3, 6.3]) and not treated with clozapine (M = 4.9 pg/mL, 95% confidence interval: [4.0, 5.8]). Exploratory, hypothesis-generating analyses found weak correlations in treatment-resistant schizophrenia, between NfL and clozapine levels (Spearman’s r = 0.258, 95% confidence interval: [0.034, 0.457]), dyslipidaemia (r = 0.280, 95% confidence interval: [0.064, 0.470]) and a negative correlation with weight (r = −0.305, 95% confidence interval: [−0.504, −0.076]). Conclusion: Treatment-resistant schizophrenia does not appear to be associated with neuronal, particularly axonal degeneration. Further studies are warranted to investigate the utility of NfL to differentiate treatment-resistant schizophrenia from neurodegenerative disorders such as behavioural variant frontotemporal dementia, and to explore NfL in other stages of schizophrenia such as the prodome and first episode

Phospho-HDAC6 Gathers Into Protein Aggregates in Parkinson’s Disease and Atypical Parkinsonisms

HDAC6 is a unique histone deacetylase that targets cytoplasmic non-histone proteins and has a specific ubiquitin-binding activity. Both of these activities are required for HDAC6-mediated formation of aggresomes, which contain misfolded proteins that will ultimately be degraded via autophagy. HDAC6 deacetylase activity is increased following phosphorylation on serine 22 (phospho-HDAC6). In human, HDAC6 localizes in neuronal Lewy bodies in Parkinson\u2019s disease (PD) and in oligodendrocytic Papp\u2013Lantos bodies in multiple system atrophy (MSA). However, the expression of phospho-HDAC6 in post-mortem human brains is currently unexplored. Here, we evaluate and compare the distribution of HDAC6 and its phosphorylated form in human brains obtained from patients affected by three forms of parkinsonism: two synucleinopathies (PD and MSA) and a tauopathy (progressive supranuclear palsy, PSP). We find that both HDAC6 and its phosphorylated form localize with pathological protein aggregates, including \u3b1-synuclein-positive Lewy bodies in PD and Papp\u2013Lantos bodies in MSA, and phospho-tau-positive neurofibrillary tangles in PSP. We further find a direct interaction of HDAC6 with \u3b1-synuclein with proximity ligation assay (PLA) in neuronal cell of PD patients. Taken together, our findings suggest that both HDAC6 and phospho-HDAC6 regulate the homeostasis of intra-neuronal proteins in parkinsonism

Correspondence Between Cognitive and Audiological Evaluations Among the Elderly: A Preliminary Report of an Audiological Screening Model of Subjects at Risk of Cognitive Decline With Slight to Moderate Hearing Loss

Epidemiological studies show increasing prevalence rates of cognitive decline and hearing loss with age, particularly after the age of 65 years. These conditions are reported to be associated, although conclusive evidence of causality and implications is lacking. Nevertheless, audiological and cognitive assessment among elderly people is a key target for comprehensive and multidisciplinary evaluation of the subject's frailty status. To evaluate the use of tools for identifying older adults at risk of hearing loss and cognitive decline and to compare skills and abilities in terms of hearing and cognitive performances between older adults and young subjects, we performed a prospective cross-sectional study using supraliminal auditory tests. The relationship between cognitive assessment results and audiometric results was investigated, and reference ranges for different ages or stages of disease were determined. Patients older than 65 years with different degrees of hearing function were enrolled. Each subject underwent an extensive audiological assessment, including tonal and speech audiometry, Italian Matrix Sentence Test, and speech audiometry with logatomes in quiet. Cognitive function was screened and then verified by experienced clinicians using the Montreal Cognitive Assessment Score, the Geriatric Depression Scale, and further investigations in some. One hundred twenty-three subjects were finally enrolled during 2016-2019: 103 were >65 years of age and 20 were younger participants (as controls). Cognitive functions showed a correlation with the audiological results in post-lingual hearing-impaired patients, in particular in those affected by slight to moderate hearing loss and aged more than 70 years. Audiological testing can thus be useful in clinical assessment and identification of patients at risk of cognitive impairment. The study was limited by its sample size (CI 95%; CL 10%), strict dependence on language, and hearing threshold. Further investigations should be conducted to confirm the reported results and to verify similar screening models

Ecological and social factors influence interspecific pathogens occurrence among bees

The interspecific transmission of pathogens can occur frequently in the environment. Among wild bees, the main spillover cases are caused by pathogens associated with Apis mellifera, whose colonies can act as reservoirs. Due to the limited availability of data in Italy, it is challenging to accurately assess the impact and implications of this phenomenon on the wild bee populations. In this study, a total of 3372 bees were sampled from 11 Italian regions within the BeeNet project, evaluating the prevalence and the abundance of the major honey bee pathogens (DWV, BQCV, ABPV, CBPV, KBV, Nosema ceranae, Ascosphaera apis, Crithidia mellificae, Lotmaria passim, Crithidia bombi). The 68.4% of samples were positive for at least one pathogen. DWV, BQCV, N. ceranae and CBPV showed the highest prevalence and abundance values, confirming them as the most prevalent pathogens spread in the environment. For these pathogens, Andrena, Bombus, Eucera and Seladonia showed the highest mean prevalence and abundance values. Generally, time trends showed a prevalence and abundance decrease from April to July. In order to predict the risk of infection among wild bees, statistical models were developed. A low influence of apiary density on pathogen occurrence was observed, while meteorological conditions and agricultural management showed a greater impact on pathogen persistence in the environment. Social and biological traits of wild bees also contributed to defining a higher risk of infection for bivoltine, communal, mining and oligolectic bees. Out of all the samples tested, 40.5% were co-infected with two or more pathogens. In some cases, individuals were simultaneously infected with up to five different pathogens. It is essential to increase knowledge about the transmission of pathogens among wild bees to understand dynamics, impact and effects on pollinator populations. Implementing concrete plans for the conservation of wild bee species is important to ensure the health of wild and human-managed bees within a One-Health perspective

Are patients with GBA-Parkinson disease good candidates for deep brain stimulation? A longitudinal multicentric study on a large Italian cohort

Background: GBA variants increase the risk of developing Parkinson disease (PD) and influence its outcome. Deep brain stimulation (DBS) is a recognised therapeutic option for advanced PD. Data on DBS long-term outcome in GBA carriers are scarce. Objective: To elucidate the impact of GBA variants on long-term DBS outcome in a large Italian cohort. Methods: We retrospectively recruited a multicentric Italian DBS-PD cohort and assessed: (1) GBA prevalence; (2) pre-DBS clinical features; and (3) outcomes of motor, cognitive and other non-motor features up to 5 years post-DBS. Results: We included 365 patients with PD, of whom 73 (20%) carried GBA variants. 5-year follow-up data were available for 173 PD, including 32 mutated subjects. GBA-PD had an earlier onset and were younger at DBS than non-GBA-PD. They also had shorter disease duration, higher occurrence of dyskinesias and orthostatic hypotension symptoms. At post-DBS, both groups showed marked motor improvement, a significant reduction of fluctuations, dyskinesias and impulsive-compulsive disorders (ICD) and low occurrence of most complications. Only cognitive scores worsened significantly faster in GBA-PD after 3 years. Overt dementia was diagnosed in 11% non-GBA-PD and 25% GBA-PD at 5-year follow-up. Conclusions: Evaluation of long-term impact of GBA variants in a large Italian DBS-PD cohort supported the role of DBS surgery as a valid therapeutic strategy in GBA-PD, with long-term benefit on motor performance and ICD. Despite the selective worsening of cognitive scores since 3 years post-DBS, the majority of GBA-PD had not developed dementia at 5-year follow-up