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Objective To investigate the cerebellar inhibitory influence on the primary motor cortex in patients with focal dystonia using a cerebellar continuous theta-burst stimulation protocol (cTBS) and to evaluate any relationship with movement abnormalities. Methods Thirteen patients with focal hand dystonia, 13 patients with cervical dystonia and 13 healthy subjects underwent two sessions: (i) cTBS over the cerebellar hemisphere (real cTBS) and (ii) cTBS over the neck muscles (sham cTBS). The effects of cerebellar cTBS were quantified as excitability changes in the contralateral primary motor cortex, as well as possible changes in arm and neck movements in patients. Results Real cerebellar cTBS reduced the excitability in the contralateral primary motor cortex in healthy subjects and in patients with cervical dystonia, though not in patients with focal hand dystonia. There was no correlation between changes in primary motor cortex excitability and arm and neck movement kinematics in patients. There were no changes in clinical scores or in kinematic measures, after either real or sham cerebellar cTBS in patients. Conclusions The reduced cerebellar inhibitory modulation of primary motor cortex excitability in focal dystonia may be related to the body areas affected by dystonia as opposed to being a widespread pathophysiological abnormality. Significance The present study yields information on the differential role played by the cerebellum in the pathophysiology of different focal dystonias.

Introduction The Geriatric Depression Scale (GDS) is commonly used to assess depressive symptoms, but its psychometric properties have never been examined in Italian people with Parkinson's disease (PD). The aim of this study was to study the reliability and validity of the Italian version of the GDS in a sample of PD patients. Methods The GDS was administered to 74 patients with PD in order to study its internal consistency, test-retest reliability, construct, and discriminant validity. Results The internal consistency of GDS was excellent (α = 0.903), as well as the test-retest reliability (ICC = 0.941 [95% CI: 0.886–0.970]). GDS showed a strong correlation with instruments related to the depression (ρ = 0.880) in PD (ρ = 0.712) and a weak correlation with generic measurement instruments (−0.320 < ρ <−0.217). An area under the curve of 0.892 (95% CI 0.809–0.975) indicated a moderate capability to discriminate depressed patients to nondepressed patient, with a cutoff value between 15 and 16 points that predicts depression (sensitivity = 87%; specificity = 82%). Conclusion The GDS is a reliable and valid tool in a sample of Italian PD subjects; this scale can be used in clinical and research contexts.

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In the testis, endothelin-1 (ET-1) is produced by Sertoli cells, and it has been proposed to be a paracrine factor participating in the regulation of tubular and interstitial function. The response of purified testicular peritubular myoid cells (TPMC) to ET-1 was investigated in the present study. TPMC expressed a single class of high-affinity receptors that were shown by competitive binding experiments with sarafotoxin-6c to belong to the ETA subtype. The binding of ET-1 to TPMC was followed by rapid internalization of the receptor-ligand complex. ET-1 induced a prompt rise in intracellular Ca2+ concentration that was blunted in Ca(2+)-free medium and in the presence of Mn2+ or of voltage-operated-calcium-channel (VOC) blockers, indicating that both Ca2+ mobilization from intracellular stores and extracellular Ca2+ influx were involved. Thymidine uptake was promoted by ET-1 in a time-dependent manner, and the use of cyclo[D-Asp-L-Pro-D-Val-L-Leu-D-Trp] (BQ123) reduced the incorporation of thymidine. Protein kinase C (PKC) inhibition (100 nM calphostin C) abolished the ET-1 mitogenic effect. ET-1 also promoted TPMC contraction, as evaluated in collagen lattices, in a dose-related manner, with the half-maximal response observed at 1 nM. As in the case of mitogenesis, BQ123 blunted ET-1-induced contraction. PKC inhibition abolished ET-1-induced contraction. These findings indicate that ET-1 promotes DNA synthesis and contraction of TPMC and that both effects are mediated by PKC; they suggest as well that ET-1 may have a physiological role in the interaction between Sertoli cells and TPMC.

The present study documents that adrenomedullin (AM), a vasoactive peptide originally identified in pheochromocytoma tissue and present in the testis, in vitro affects the function of testicular peritubular myoid cells (TPMC), a contractile cell type located in the seminiferous tubule wall. AM stimulated cAMP production by cultured TPMC taken from 16-day-old rats, and this effect was completely inhibited by the AM antagonist AM-(22-52) and partially by the CGRP (calcitonin gene-related peptide) antagonist CGRP-(8-37). Studies on TPMC contractile activity documented that AM inhibits TPMC contraction induced by endothelin-1 (ET-1) and that its effect is antagonized by AM-(22-52). Neutralizing AM produced by TPMC with the addition of anti-AM antibody induced a significant increase of ET-1-induced contraction. When exposed to the protein kinase A inhibitor H-89, AM inhibitory activity on ET-1-induced TPMC contraction was suppressed, whereas the nitric oxide synthase inhibitor N:(G)-nitro-L-arginine methyl esther did not modify AM activity. In conclusion, our study indicates that AM stimulates cAMP production and inhibits the contraction induced by ET-1 in TPMC in vitro, and that AM produced by TPMC has an autocrine effect. We propose that AM may have a role in the control of seminiferous tubule contraction.

Background Possible pathophysiological mechanisms underlying Parkinson's disease (PD) clinical subtypes are unknown. The objective of this study was to identify pathophysiological substrate of PD subtypes using neurophysiological techniques. Methods One hundred de novo PD patients participated. We collected patient demographic and clinical data, which were used to perform a hierarchical cluster analysis. The neurophysiological assessment tested primary motor cortex excitability and plasticity using transcranial magnetic stimulation. To evaluate motor performance, we performed a kinematic analysis of fast index finger abduction. To investigate sensory function and sensorimotor mechanisms, we measured the somatosensory temporal discrimination threshold at rest and during movement, respectively. Results Hierarchical cluster analysis identified 2 clinical clusters. Cluster I (“mild motor‐predominant”) included patients who had milder motor and nonmotor symptoms severity than cluster II patients, who had a combination of severe motor and nonmotor manifestations (diffuse malignant). We observed that the diffuse malignant subtype had increased cortical excitability and reduced plasticity compared with the mild motor‐predominant subtype. Kinematic analysis of motor performance demonstrated that the diffuse malignant subtype was significantly slower than the mild motor‐predominant subtype. Conversely, we did not observe any significant differences in sensory function or sensorimotor integration between the two PD subtypes. Conclusions De novo PD subtypes showed different patterns of motor system dysfunction, whereas sensory function and sensorimotor integration mechanisms did not differ between subtypes. Our findings suggest that the subtyping of PD patients is not a mere clinical classification but reflects different pathophysiological mechanisms. Neurophysiological parameters may represent promising biomarkers to evaluate PD subtypes and their progression. © 2020 International Parkinson and Movement Disorder Society

Introduction. The clinical, social, and economic implications of Parkinson's disease (PD) are significant; disability occurs leading to a low quality of life (QoL). Information on the QoL of patients with PD and studies on the relationship between QoL and motor and cognitive function are necessary for both research and clinical use to make informed decisions in healthcare and rehabilitation. The aim of this study was to determine which scales are most used to assess QoL in patients with PD. Area covered. A literature search was conducted in MEDLINE, Scopus, CINAHL, PsycINFO, and Web of Science. Two authors independently identified eligible studies based on predefined inclusion criteria and extracted the data. Study quality and the risk of bias were assessed using the COSMIN checklist. Expert opinion. 116 suitable studies were included, and 42 different instruments were identified.The most frequently used scales were the 39-items and 8-items Parkinson's Disease Questionnaire (PDQ-39) (PDQ-8). These findings suggest further investigation of existing PD outcome measures would benefit patients, researchers, and clinicians. Validated, universal outcome measures are required to allow comparisons across practice; therefore, we recommend that future researchers use a common set of outcome assessments based on the results of this review.