Speech impairment in Parkinson’s disease: acoustic analysis of unvoiced consonants in Italian native speakers

The study of the influence of Parkinson’s Disease (PD) on vocal signals has received much attention over the last decades. Increasing interest has been devoted to articulation and acoustic characterization of different phonemes. Method: In this study we propose the analysis of the Transition Regions (TR) of specific phonetic groups to model the loss of motor control and the difficulty to start/stop movements, typical of PD patients. For this purpose, we extracted 60 features from pre-processed vocal signals and used them as input to several machine learning models. We employed two data sets, containing samples from Italian native speakers, for training and testing. The first dataset - 28 PD patients and 22 Healthy Control (HC) - included recordings in optimal conditions, while in the second one - 26 PD patients and 18 HC- signals were collected at home, using non-professional microphones. Results: We optimized two support vector machine models for the application in controlled noise conditions and home environments, achieving 98% ± 1.1 and 88% ± 2.8 accuracy in 10-fold cross-validation, respectively. Conclusion: This study confirms the high capability of the TRs to discriminate between PD patients and healthy controls, and the feasibility of automatic PD assessment using voice recordings. Moreover, the promising performance of the implemented model discloses the option of voice processing using low-cost devices and domestic recordings, possibly self-managed by the patients themselves

Subcutaneous administration of tocilizumab is effective in myointimal hyperplasia remodelling in refractory Takayasu arteritis

Takayasu arteritis (TA) is a chronic inflammatory disease of unknown origin that involves large and mediumsized arteries, primarily the aorta and its major branches. TA is a therapeutic challenge because corticosteroids and conventional immunosuppressive agents are not always effective or safe. Interleukin 6 (IL-6) has emerged as a key cytokine in the pathogenesis of TA and its serum levels have been shown to well correlate with disease activity. We report a 19 years old female patient with TA refractory to conventional immunosuppressive agents, successfully treated with subcutaneous tocilizumab, a humanized monoclonal antibody against IL-6 receptor, in which ultrasonography (US) was used as imaging tool to follow up the patient. Currently, clinical indices of disease activity, inflammatory markers, carotid intima media thickness (cIMT) as well as carotid pulse wave velocity (cPWV) normalised, while the prednisone dosage has been tapered. Tocilizumab appears to be a good option in refractory TA, with a remarkable steroid-sparing effect. In addition, it seems to have a favourable effect on endothelial function, as it improved cIMT and PWV

Assessment of Axial Postural Abnormalities in Parkinsonism: Automatic Picture Analysis Software

BackgroundSoftware-based measurements of axial postural abnormalities in Parkinson's disease (PD) are the gold standard but may be time-consuming and not always feasible in clinical practice. An automatic and reliable software to accurately obtain real-time spine flexion angles according to the recently proposed consensus-based criteria would be a useful tool for both research and clinical practice. ObjectiveWe aimed to develop and validate a new software based on Deep Neural Networks to perform automatic measures of PD axial postural abnormalities. MethodsA total of 76 pictures from 55 PD patients with different degrees of anterior and lateral trunk flexion were used for the development and pilot validation of a new software called AutoPosturePD (APP); postural abnormalities were measured in lateral and posterior view using the freeware NeuroPostureApp (gold standard) and compared with the automatic measurement provided by the APP. Sensitivity and specificity for the diagnosis of camptocormia and Pisa syndrome were assessed. ResultsWe found an excellent agreement between the new APP and the gold standard for lateral trunk flexion (intraclass correlation coefficient [ICC] 0.960, IC95% 0.913-0.982, P < 0.001), anterior trunk flexion with thoracic fulcrum (ICC 0.929, IC95% 0.846-0.968, P < 0.001) and anterior trunk flexion with lumbar fulcrum (ICC 0.991, IC95% 0.962-0.997, P < 0.001). Sensitivity and specificity were 100% and 100% for detecting Pisa syndrome, 100% and 95.5% for camptocormia with thoracic fulcrum, 100% and 80.9% for camptocormia with lumbar fulcrum. ConclusionsAutoPosturePD is a valid tool for spine flexion measurement in PD, accurately supporting the diagnosis of Pisa syndrome and camptocormia

How resistant are levodopa-resistant axial symptoms? Response of freezing, posture, and voice to increasing levodopa intestinal infusion rates in Parkinson disease

Background and purpose: Treatment of freezing of gait (FoG) and other Parkinson disease (PD) axial symptoms is challenging. Systematic assessments of axial symptoms at progressively increasing levodopa doses are lacking. We sought to analyze the resistance to high levodopa doses of FoG, posture, speech, and altered gait features presenting in daily-ON therapeutic condition. Methods: We performed a pre-/postinterventional study including patients treated with levodopa/carbidopa intestinal gel infusion (LCIG) with disabling FoG in daily-ON condition. Patients were evaluated at their usual LCIG infusion rate (T1), and 1 h after 1.5× (T2) and 2× (T3) increase of the LCIG infusion rate by quantitative outcome measures. The number of FoG episodes (primary outcome), posture, speech, and gait features were objectively quantified during a standardized test by a blinded rater. Changes in motor symptoms, dyskinesia, and plasma levodopa concentrations were also analyzed. Results: We evaluated 16 patients with a mean age of 69 ± 9.4 years and treated with LCIG for a mean of 2.2 ± 2.1 years. FoG improved in 83.3% of patients by increasing the levodopa doses. The number of FoG episodes significantly decreased (mean = 2.3 at T1, 1.7 at T2, 1.2 at T3; p = 0.013). Posture and speech features did not show significant changes, whereas stride length (p = 0.049), turn duration (p = 0.001), and turn velocity (p = 0.024) significantly improved on doubling the levodopa infusion rate. Conclusions: In a short-term evaluation, the increase of LCIG dose can improve "dopa-resistant" FoG and gait issues in most advanced PD patients with overall good control of motor symptoms in the absence of clinically significant dyskinesia

MTF1, a classic metal sensing transcription factor, promotes myogenesis in response to copper [preprint]

MTF1 is a conserved metal-binding transcription factor in eukaryotes that binds to conserved DNA sequence motifs, termed metal response elements (MREs). MTF1 responds to metal excess and deprivation, protects cells from oxidative and hypoxic stresses, and is required for embryonic development in vertebrates. We used multiple strategies to identify an unappreciated role for MTF1 and copper (Cu) in cell differentiation. Upon initiation of myogenesis from primary myoblasts, MTF1 expression increased, as did nuclear localization. Mtf1 knockdown impaired differentiation, while addition of non-toxic concentrations of Cu+ enhanced MTF1 expression and promoted myogenesis. Cu+ bound stoichiometrically to a C-terminus tetra-cysteine of MTF1. MTF1 bound to chromatin at the promoter regions of myogenic genes and binding was stimulated by copper. MTF1 formed a complex with MyoD at myogenic promoters, the master transcriptional regulator of the myogenic lineage. These studies establish novel mechanisms by which copper and MTF1 regulate gene expression in myoblast differentiation

Natural Course of COVID-19 and Independent Predictors of Mortality.

Background: During the SARS-CoV-2 pandemic, several biomarkers were shown to be helpful in determining the prognosis of COVID-19 patients. The aim of our study was to evaluate the prognostic value of N-terminal pro-Brain Natriuretic Peptide (NT-pro-BNP) in a cohort of patients with COVID-19. Methods: One-hundred and seven patients admitted to the Covid Hospital of Messina University between June 2022 and January 2023 were enrolled in our study. The demographic, clinical, biochemical, instrumental, and therapeutic parameters were recorded. The primary outcome was in-hospital mortality. A comparison between patients who recovered and were discharged and those who died during the hospitalization was performed. The independent parameters associated with in-hospital death were assessed by multivariable analysis and a stepwise regression logistic model. Results: A total of 27 events with an in-hospital mortality rate of 25.2% occurred during our study. Those who died during hospitalization were older, with lower GCS and PaO2/FiO2 ratio, elevated D-dimer values, INR, creatinine values and shorter PT (prothrombin time). They had an increased frequency of diagnosis of heart failure (p < 0.0001) and higher NT-pro-BNP values. A multivariate logistic regression analysis showed that higher NT-pro-BNP values and lower PT and PaO2/FiO2 at admission were independent predictors of mortality during hospitalization. Conclusions: This study shows that NT-pro-BNP levels, PT, and PaO2/FiO2 ratio are independently associated with in-hospital mortality in subjects with COVID-19 pneumonia. Further longitudinal studies are warranted to confirm the results of this study

Comparison of permutationally invariant polynomials, neural networks, and Gaussian approximation potentials in representing water interactions through many-body expansions.

The accurate representation of multidimensional potential energy surfaces is a necessary requirement for realistic computer simulations of molecular systems. The continued increase in computer power accompanied by advances in correlated electronic structure methods nowadays enables routine calculations of accurate interaction energies for small systems, which can then be used as references for the development of analytical potential energy functions (PEFs) rigorously derived from many-body (MB) expansions. Building on the accuracy of the MB-pol many-body PEF, we investigate here the performance of permutationally invariant polynomials (PIPs), neural networks, and Gaussian approximation potentials (GAPs) in representing water two-body and three-body interaction energies, denoting the resulting potentials PIP-MB-pol, Behler-Parrinello neural network-MB-pol, and GAP-MB-pol, respectively. Our analysis shows that all three analytical representations exhibit similar levels of accuracy in reproducing both two-body and three-body reference data as well as interaction energies of small water clusters obtained from calculations carried out at the coupled cluster level of theory, the current gold standard for chemical accuracy. These results demonstrate the synergy between interatomic potentials formulated in terms of a many-body expansion, such as MB-pol, that are physically sound and transferable, and machine-learning techniques that provide a flexible framework to approximate the short-range interaction energy terms.This work was supported by the National Science Foundation through Grant No. ACI-1642336 (to F.P. and A.W.G.). This work used the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation Grant No. ACI-1548562. J.B. is grateful for a Heisenberg professorship funded by the DFG (No. Be3264/11-2). E.Sz. would like to acknowledge the support of the Peterhouse Research Studentship and the support of BP International Centre for Advanced Materials (ICAM). M.C. was supported by the European Research Council under the European Union’s Horizon 2020 research and innovation programme (Grant Agreement No. 677013-HBMAP). G.I. acknowledges funding from the Fondazione Zegn

3D Ordering at the Liquid–Solid Polar Interface of Nanowires

The nature of the liquid–solid interface determines the characteristics of a variety of physical phenomena, including catalysis, electrochemistry, lubrication, and crystal growth. Most of the established models for crystal growth are based on macroscopic thermodynamics, neglecting the atomistic nature of the liquid–solid interface. Here, experimental observations and molecular dynamics simulations are employed to identify the 3D nature of an atomic‐scale ordering of liquid Ga in contact with solid GaAs in a nanowire growth configuration. An interplay between the liquid ordering and the formation of a new bilayer is revealed, which, contrary to the established theories, suggests that the preference for a certain polarity and polytypism is influenced by the atomic structure of the interface. The conclusions of this work open new avenues for the understanding of crystal growth, as well as other processes and systems involving a liquid–solid interface