Rest tremor in Parkinson's disease: body distribution and time of appearance

Objective To assess body distribution and timing of appearance of rest tremor in Parkinson's disease. Methods Information was obtained by a computerized database containing historical information collected at the first visit and data collected during the subsequent follow-up visits. Information on rest tremor developed during the follow-up could be therefore obtained by our own observation in a proportion of patients. Results Among 289 patients, rest tremor was reported at disease onset in 65.4% of cases and detected at last follow-up examination in 74.4% of patients. Analysis of patients who did not report rest tremor at disease onset indicated that 26% of such patients (9% in the overall population) manifested rest tremor over the disease course. Rest tremor spread to new sites in 39% of patients who manifested rest tremor at disease onset. Regardless of tremor presentation at disease onset or during the follow-up, upper limb was the most frequent tremor localization. Over the follow-up, rest tremor developed faster in the upper limb than in other body sites. The risk of developing rest tremor during the follow-up was not affected by sex, side of motor symptom onset and site of tremor presentation. However, age of disease onset > 63 years was associated with an increased risk of rest tremor spread. Conclusions This study provides new information about body distribution and timing of rest tremor appearance during the course of early stages of Parkinson's disease that may help clinicians in patients' counselling

Coronary Collateral Circulation: A New Predictor of Mortality in Heart Transplant Recipients With Allograft Vasculopathy

Background: Coronary collateral arteries (CCAs) are anastomotic channels between vessels; although beneficial in atherosclerosis, their role in heart transplantation (HT) recipients is underinvestigated. CCAs initially develop as microcirculation and cardiac allograft vasculopathy (CAV), promoting immune-dependent proliferative angiogenic response, and play a role in their development. In our hypothesis, ischemia induced by coronary microvascular dysfunction (CMD) triggers the development of CCAs, which are, in turn, less functional as affected by CAV themselves. Methods: One hundred twenty-one patients receiving HT at our institution were retrospectively evaluated and were included if transthoracic echocardiography with coronary flow velocity reserve (CFVR) assessment and coronary angiography were performed. CMD was defined as CFVR of ≤2.5. Patients with CAV were enrolled, and their angiograms were reviewed to evaluate the presence of CCAs. Cardiovascular mortality was assessed as the main clinical outcome. Results: Forty patients were found to have CCAs. Patients with CCAs have lower CFVR than those without CCAs (2.22 ± 0.72 versus 2.69 ± 0.92;P = 0.003), reflecting in different rates of CMD in the 2 groups (72.5% versus 37%; P < 0.001). CMD is associated with higher CAV grades (P < 0.001), which are also associated with CCAs (P < 0.001). Patients with poorly developed CCAs have lower CFVR (P < 0.001). At multivariable analysis, CMD (P = 0.008) and higher CAV grades (P = 0.005) are independent predictors of CCAs. During the median follow-up time of 10.2 (6.6-13.3) y, patients with CCAs have been found to have higher mortality than those without CCAs (57.5% versus 32.1%; P = 0.007). CCAs are associated with a lower probability of survival also in patients with CMD (P < 0.001) and are independent predictors of mortality (P < 0.001). Conclusions: Our results demonstrate an interplay between CAV, CMD, and CCAs. We confirm that CAV is associated with CMD, and we show, for the first time, that CMD is associated with CCAs. CCAs are pathophysiologically associated with more severe graft vasculopathy and independently predict mortality after HT

Prevalence of Thromboembolic Complications in COVID-19 Infection: A Systematic Review and Meta-Analysis

Introduction: The coronavirus disease (COVID-19) infection is proved to be involved in the onset of thromboembolism episodes. This study aims to evaluate the prevalence of thromboembolic complications in patients with COVID-19 from March until May 2020. Methods: A literature review was conducted in MEDLINE (via PubMed), Scopus, Embase, Cochrane, and CINHAL without any language and date of publication restriction (Prospero registration number CRD42020186925). The inclusion criteria were as following: 1) patients with diagnosis of COVID-19; 2) occurrence of thromboembolic event, and 3) patients older than 18 years of age. A multi-variable random effects model was computed accounting for correlations among outcomes by considering a heterogeneous compound symmetry covariance matrix. Results: Observational studies included 2,442 participants from 268 to 7,999 participants per study, 1,014 (41.52%) were male and 825 (33.78%) were female. The multi-variable pooled event rate of acute myocardial infarction was rare, estimated to be 0.03 (95% confidence interval [CI]: 0.00–0.07; p=0.23); this is also true for the meta-analytical estimate of disseminated intravascular disease which was 0.04 (95% CI: 0.00–0.08; p=0.03). Conversely, other events were found to be more frequent. Indeed, the pooled proportion of pulmonary embolism was 0.14 (95% CI: 0.08–0.20; p<0.001), while the venous thromboembolic event rate is 0.15 (95% CI: 0.09-0.30; p=0.04). The pooled intrahospital mortality rate was equal to 0.12 (95% CI: 0.08–0.16; p<0.001). Conclusions: Thromboembolic events, particularly venous thromboembolic event rate and pulmonary embolism, are a frequent complication in patients hospitalised with COVID-19. These findings suggest that the threshold for clinical suspicion should be low to trigger prompt diagnostic testing and that evaluation of therapeutic treatment should be considered in patients in intensive care units with COVID-19

PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability

The protein phosphatase 2A complex (PP2A), the major Ser/Thr phosphatase in the brain, is involved in a number of signalling pathways and functions, including the regulation of crucial proteins for neurodegeneration, such as alpha-synuclein, tau and LRRK2. Here, we report the identification of variants in the PTPA/PPP2R4 gene, encoding a major PP2A activator, in two families with early-onset parkinsonism and intellectual disability. We carried out clinical studies and genetic analyses, including genome-wide linkage analysis, whole-exome sequencing, and Sanger sequencing of candidate variants. We next performed functional studies on the disease-associated variants in cultured cells and knock-down of ptpa in Drosophila melanogaster. We first identified a homozygous PTPA variant, c.893T&gt;G (p.Met298Arg), in patients from a South African family with early-onset parkinsonism and intellectual disability. Screening of a large series of additional families yielded a second homozygous variant, c.512C&gt;A (p.Ala171Asp), in a Libyan family with a similar phenotype. Both variants co-segregate with disease in the respective families. The affected subjects display juvenile-onset parkinsonism and intellectual disability. The motor symptoms were responsive to treatment with levodopa and deep brain stimulation of the subthalamic nucleus. In overexpression studies, both the PTPA p.Ala171Asp and p.Met298Arg variants were associated with decreased PTPA RNA stability and decreased PTPA protein levels; the p.Ala171Asp variant additionally displayed decreased PTPA protein stability. Crucially, expression of both variants was associated with decreased PP2A complex levels and impaired PP2A phosphatase activation. PTPA orthologue knock-down in Drosophila neurons induced a significant impairment of locomotion in the climbing test. This defect was age-dependent and fully reversed by L-DOPA treatment. We conclude that bi-allelic missense PTPA variants associated with impaired activation of the PP2A phosphatase cause autosomal recessive early-onset parkinsonism with intellectual disability. Our findings might also provide new insights for understanding the role of the PP2A complex in the pathogenesis of more common forms of neurodegeneration.</p

A new attempt at automatic data processing in Magnetotellurics

none2Considering the magnetotelluric (MT) signal in its physical reality as a stochastic process, we present here a new methodology for the search and analysis of the wave packets which are most compatible with theoretical calculation requirements. In adapting the length of the physical data blocks to a small number of oscillations of the signal, we are able to identify those data ensembles which show particularly high rotated coherence values (higher than 0.9). An example of such calculations is supplied by means of the analysis of an MT sounding which demonstrates the validity of this procedure. © 1979.noneILICETO V.; G. SANTARATOIliceto, V.; Santarato, Giovann

On the interference of man-made EM fields in the magnetotelluric 'dead band'

none2During processing of magnetotelluric (MT) data, acquired in a survey carried out in southern Italy, a problem was encountered, connected with the so-called ‘dead band’ of the MT signal (around 1 Hz). In the apparent resistivity curves of some MT soundings, a V-shaped minimum appeared, centred on the dead-band frequency. This phenomenon turned out to originate from a strong artificial source and was not due to a downward bias of the robust processing techniques adopted. The source distance from the MT sounding locations was such that the V-shaped minimum fell precisely in the dead-band frequency range. Theoretical considerations about fields generated by an electric dipole led us to the probable identification of the source as the d.c.-powered railway between Naples and Bari.openILICETO V; SANTARATO G.Iliceto, V; Santarato, Giovann

On the possibilities of the telluric method: some results on faulted structures.

none2--noneIliceto V.; Santarato G.Iliceto, V.; Santarato, Giovann

On the possibility of the telluric method: some results on faulted structures

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2D MODELING OF RESISTIVITY AND MAGNETOTELLURIC DATA FROM THE BELVEDERE-SPINELLO SALT MINE, ITALY

none3The Belvedere Spinello salt mine is located in the Catanzaro Province of Calabria in Southern Italy. An extensive mining program has caused the development of Underground cavities filled with brine and the migration of this brine has been of great environmental concern to the mine owners. This paper presents the results of a multidimensional interpretation of a two-phase resistivity and magnetotelluric (MT) survey that was performed in an attempt to determine the complex conductivity structure of the mine area and to gain information on brine development and migration pathways. Key resistivity soundings were interpreted using a 2.5D algorithm based on the Polozhii decomposition method. The MT data were interpreted using a 2D finite-element code. A conductivity model was developed, integrating available geological and drill-hole information. The interpretation of the MT data, collected five years after the acquisition of the resistivity data, shows a conductive feature of depth that is not resolved in the resistivity interpretation. This feature has been interpreted as a thick brine zone that has developed as a result of mining during the interval between the resistivity and the MT measurements.openILICETO V; SANTARATO G.; ZERILLI AIliceto, V; Santarato, Giovanni; Zerilli, A