ABSTRACT
Over the past three decades, substantial advancements have occurred in non-invasive brain stimulation (NIBS). These developments encompass various non-invasive techniques aimed at modulating brain function. Among the most widely utilized methods today are transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES), which include direct- or alternating-current transcranial stimulation (tDCS/tACS). In addition to these established techniques, newer modalities have emerged, broadening the scope of non-invasive neuromodulation approaches available for research and clinical applications in movement disorders, particularly for Parkinson's disease (PD) and, to a lesser extent, atypical Parkinsonism (AP). All NIBS techniques offer the opportunity to explore a wide range of neurophysiological mechanisms and exert influence over distinct brain regions implicated in the pathophysiology of Parkinsonism. This paper's first aim is to provide a brief overview of the historical background and underlying physiological principles of primary NIBS techniques, focusing on their translational relevance. It aims to shed light on the potential identification of biomarkers for diagnostic and therapeutic purposes, by summarising available experimental data on individuals with Parkinsonism. To date, despite promising findings indicating the potential utility of NIBS techniques in Parkinsonism, their integration into clinical routine for diagnostic or therapeutic protocols remains a subject of ongoing investigation and scientific debate. In this context, this paper addresses current unsolved issues and methodological challenges concerning the use of NIBS, focusing on the importance of future research endeavours for maximizing the efficacy and relevance of NIBS strategies for individuals with Parkinsonism.
ABSTRACT
Coastal waters face significant anthropogenic stress, particularly from tourism, exacerbating pollution, especially in areas like touristic islands. Ischia, the largest island in the Gulf of Naples and part of the Regno di Nettuno Marine Protected Area, suffers from pollution due to tourism and maritime traffic. During the initial SARS-CoV-2 lockdown from March to June 2020, Ischia was isolated, providing a unique opportunity to study pollutant release and its impact on coastal ecosystems. Adult Mytilus galloprovincialis mussels were transplanted to three sites on the island for active biomonitoring. Accumulation of chemicals in tissues and biomarkers related to metabolism, detoxification, and oxidative stress were measured. Results indicated that pollutants from daily activities entered the sea, affecting filter feeders. Translocated organisms showed modulated metabolic functions and biochemical changes, highlighting coastal vulnerability and calling for conservation efforts.
Subject(s)
Biological Monitoring , Mytilus , Animals , Humans , COVID-19 , Tourism , Environmental Monitoring , Water Pollutants, Chemical/analysis , Islands , Human Activities , Italy , SARS-CoV-2ABSTRACT
BACKGROUND: Subtle parkinsonian signs, i.e., rest tremor and bradykinesia, are considered soft signs for defining essential tremor (ET) plus. OBJECTIVES: Our study aimed to further characterize subtle parkinsonian signs in a relatively large sample of ET patients from a clinical and neurophysiological perspective. METHODS: We employed clinical scales and kinematic techniques to assess a sample of 82 ET patients. Eighty healthy controls matched for gender and age were also included. The primary focus of our study was to conduct a comparative analysis of ET patients (without any soft signs) and ET-plus patients with rest tremor and/or bradykinesia. Additionally, we investigated the asymmetry and side concordance of these soft signs. RESULTS: In ET-plus patients with parkinsonian soft signs (56.10% of the sample), rest tremor was clinically observed in 41.30% of cases, bradykinesia in 30.43%, and rest tremor plus bradykinesia in 28.26%. Patients with rest tremor had more severe and widespread action tremor than other patients. Furthermore, we observed a positive correlation between the amplitude of action and rest tremor. Most ET-plus patients had an asymmetry of rest tremor and bradykinesia. There was no side concordance between these soft signs, as confirmed through both clinical examination and kinematic evaluation. CONCLUSIONS: Rest tremor and bradykinesia are frequently observed in ET and are often asymmetric but not concordant. Our findings provide a better insight into the phenomenology of ET and suggest that the parkinsonian soft signs (rest tremor and bradykinesia) in ET-plus may originate from distinct pathophysiological mechanisms.
Subject(s)
Essential Tremor , Hypokinesia , Humans , Essential Tremor/physiopathology , Essential Tremor/diagnosis , Female , Male , Biomechanical Phenomena , Aged , Middle Aged , Hypokinesia/physiopathology , Hypokinesia/etiology , Hypokinesia/diagnosis , Severity of Illness Index , Aged, 80 and over , AdultABSTRACT
Background: Tremor disorders have various genetic causes. Case report: A 60-year-old female with a family history of tremor presented a combined tremor syndrome, transient episodes of loss of contact and speech disturbances, as well as distal painful symptoms. Genetic screening revealed a novel heterozygous missense variant in the KCNQ2 gene. Discussion: The KCNQ2 protein regulates action potential firing, and mutations in its gene are associated with epilepsy and neuropathic pain. The identified variant, although of uncertain significance, may disrupt KCNQ2 function and also play a role in tremor pathogenesis. This case highlights the importance of genetic screening in combined tremor disorders.
Subject(s)
KCNQ2 Potassium Channel , Tremor , Female , Humans , Middle Aged , KCNQ2 Potassium Channel/genetics , Mutation, Missense , Tremor/genetics , Tremor/physiopathologyABSTRACT
Substantial evidence highlights the role of the cerebellum in the pathophysiology of tremor in essential tremor (ET), although its potential involvement in altered movement execution in this condition remains unclear. This study aims to explore potential correlations between the cerebellum and basal ganglia functional connectivity and voluntary movement execution abnormalities in ET, objectively assessed with kinematic techniques. A total of 20 patients diagnosed with ET and 18 healthy subjects were enrolled in this study. Tremor and repetitive finger tapping were recorded using an optoelectronic kinematic system. All participants underwent comprehensive 3T-MRI examinations, including 3D-T1 and blood-oxygen-level dependent (BOLD) sequences during resting state. Morphometric analysis was conducted on the 3D-T1 images, while a seed-based analysis was performed to investigate the resting-state functional connectivity (rsFC) of dorsal and ventral portions of the dentate nucleus and the external and internal segments of the globus pallidus. Finally, potential correlations between rsFC alterations in patients and clinical as well as kinematic scores were assessed. Finger tapping movements were slower in ET than in healthy subjects. Compared to healthy subjects, patients with ET exhibited altered FC of both dentate and globus pallidus with cerebellar, basal ganglia, and cortical areas. Interestingly, both dentate and pallidal FC exhibited positive correlations with movement velocity in patients, differently from that we observed in healthy subjects, indicating the higher the FC, the faster the finger tapping. The findings of this study indicate the possible role of both cerebellum and basal ganglia in the pathophysiology of altered voluntary movement execution in patients with ET.
ABSTRACT
Essential tremor (ET) is a heterogeneous disorder characterized by bilateral upper limbs action tremor and, possibly, neurological signs of uncertain significance, including voluntary movement abnormalities and cognitive disturbances, i.e., the so-called 'soft' signs configuring the ET-plus definition. While motor and cognitive disturbances often coexist in ET, their interrelationship remains largely unexplored. Here we aim to further investigate the relationship between motor symptoms, objectively assessed through kinematic analysis, and cognitive dysfunctions in ET. Seventy ET patients underwent clinical examination, as well as kinematic recordings of tremor and finger tapping and a thorough cognitive assessment. We then tested clinic-demographic and kinematic differences between patients with and without cognitive abnormalities, i.e., with mild cognitive impairment (MCI). Correlation analysis served to explore potential associations between kinematic and cognitive data. Forty-three ET patients (61.42%) had MCI. ET-MCI patients exhibited reduced movement velocity during finger tapping compared to those with normal cognition (p < 0.001). Lower movement velocity during finger tapping was associated with poorer cognitive performance. Namely, we observed a correlation between movement velocity and performance on the Babcock Story Immediate and Delayed Recall Test (r = 0.52 and r = 0.45, both p < 0.001), as well as the interference memory task at 10 and 30 s (r = 0.3, p = 0.008 and r = 0.2, p = 0.03). In this study, we have provided data for a better pathophysiological interpretation of motor and cognitive signs in ET, including the role played by the cerebellum or extra-cerebellar areas, which possibly underpin both signs.
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In patients with Parkinson's disease, the connectivity between the two primary motor cortices may be altered. However, the correlation between asymmetries of abnormal interhemispheric connections and bradykinesia features has not been investigated. Furthermore, the potential effects of dopaminergic medications on this issue remain largely unclear. The aim of the present study is to investigate the interhemispheric connections in Parkinson's disease by transcranial magnetic stimulation and explore the potential relationship between interhemispheric inhibition and bradykinesia feature asymmetry in patients. Additionally, we examined the impact of dopaminergic therapy on neurophysiological and motor characteristics. Short- and long-latency interhemispheric inhibition was measured in 18 Parkinson's disease patients and 18 healthy controls, bilaterally. We also assessed the corticospinal and intracortical excitability of both primary motor cortices. We conducted an objective analysis of finger-tapping from both hands. Correlation analyses were performed to explore potential relationships among clinical, transcranial magnetic stimulation and kinematic data in patients. We found that short- and long-latency interhemispheric inhibition was reduced (less inhibition) from both hemispheres in patients than controls. Compared to controls, finger-tapping movements in patients were slower, more irregular, of smaller amplitudes and characterized by a progressive amplitude reduction during movement repetition (sequence effect). Among Parkinson's disease patients, the degree of short-latency interhemispheric inhibition imbalance towards the less affected primary motor cortex correlated with the global clinical motor scores, as well as with the sequence effect on the most affected hand. The greater the interhemispheric inhibition imbalance towards the less affected hemisphere (i.e. less inhibition from the less to the most affected primary motor cortex than that measured from the most to the less affected primary motor cortex), the more severe the bradykinesia in patients. In conclusion, the inhibitory connections between the two primary motor cortices in Parkinson's disease are reduced. The interhemispheric disinhibition of the primary motor cortex may have a role in the pathophysiology of specific bradykinesia features in patients, i.e. the sequence effect.
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OBJECTIVE: To evaluate the effects of cerebellar transcranial alternating current stimulation (tACS) delivered at cerebellar-resonant frequencies, i.e., theta (θ) and gamma (γ), on upper limb motor performance and cerebellum-primary motor cortex (M1) connectivity, as assessed by cerebellar-brain inhibition (CBI), in healthy subjects. METHODS: Participants underwent cerebellar-tACS while performing three cerebellar-dependent motor tasks: (i) rhythmic finger-tapping, (ii) arm reaching-to-grasp ('grasping') and (iii) arm reaching-to-point ('pointing') an object. Also, we evaluated possible changes in CBI during cerebellar-tACS. RESULTS: θ-tACS decreased movement regularity during the tapping task and increased the duration of the pointing task compared to sham- and γ-tACS. Additionally, θ-tACS increased the CBI effectiveness (greater inhibition). The effect of θ-tACS on movement rhythm correlated with CBI changes and less tapping regularity corresponded to greater CBI. CONCLUSIONS: Cerebellar-tACS delivered at the θ frequency modulates cerebellar-related motor behavior and this effect is, at least in part, mediated by changes in the cerebellar inhibitory output onto M1. The effects of θ-tACS may be due to the modulation of cerebellar neurons that resonate to the θ rhythm. SIGNIFICANCE: These findings contribute to a better understanding of the physiological mechanisms of motor control and provide new evidence on cerebellar non-invasive brain stimulation.
Subject(s)
Motor Cortex , Transcranial Direct Current Stimulation , Humans , Motor Cortex/physiology , Cerebellum/physiology , Upper Extremity , Theta RhythmABSTRACT
Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders with some overlapping clinical features. Hypomimia (reduced facial expressivity) is a prominent sign of PD and it is also present in AD. However, no study has experimentally assessed hypomimia in AD and compared facial expressivity between PD and AD patients. We compared facial emotion expressivity in patients with PD, AD, and healthy controls (HCs). Twenty-four PD patients, 24 AD patients and 24 HCs were videotaped during neutral facial expressions and while posing six facial emotions (anger, surprise, disgust, fear, happiness, and sadness). Fifteen raters were asked to evaluate the videos using MDS-UPDRS-III (item 3.2) and to identify the corresponding emotion from a seven-forced-choice response format. We measured the percentage of accuracy, the reaction time (RT), and the confidence level (CL) in the perceived accuracy of the raters' responses. We found the highest MDS-UPDRS 3.2 scores in PD, and higher in AD than HCs. When evaluating the posed expression captures, raters identified a lower percentage of correct answers in the PD and AD groups than HCs. There was no difference in raters' response accuracy between the PD and AD. No difference was observed in RT and CL data between groups. Hypomimia in patients correlated positively with the global MDS-UPDRS-III and negatively with Mini Mental State Examination scores. PD and AD patients have a similar pattern of reduced facial emotion expressivity compared to controls. These findings hold potential pathophysiological and clinical implications.
Subject(s)
Alzheimer Disease , Parkinson Disease , Humans , Facial Expression , Emotions/physiology , FaceABSTRACT
BACKGROUND: Opicapone (OPC) is a third-generation, selective peripheral COMT inhibitor that improves peripheral L-DOPA bioavailability and reduces OFF time and end-of-dose motor fluctuations in Parkinson's disease (PD) patients. OBJECTIVES: In this study, we objectively assessed the effects of adding OPC to L-DOPA on bradykinesia in PD through kinematic analysis of finger movements. METHODS: We enrolled 20 treated patients with PD and motor fluctuations. Patients underwent two experimental sessions (L-DOPA, L-DOPA + OPC), separated by at least 1 week. In each session, patients were clinically evaluated and underwent kinematic movement analysis of repetitive finger movements at four time points: (i) before their usual morning dose of L-DOPA (T0), (ii) 30 min (T1), (iii) 1 h and 30 min (T2), and (iv) 3 h and 30 min after the L-DOPA intake (T3). RESULTS: Movement velocity and amplitude of finger movements were higher in PD patients during the session with OPC compared to the session without OPC at all the time points tested. Importantly, the variability of finger movement velocity and amplitude across T0-T3 was significantly lower in the L-DOPA + OPC than L-DOPA session. CONCLUSIONS: This study is the first objective assessment of the effects of adding OPC to L-DOPA on bradykinesia in patients with PD and motor fluctuations. OPC, in addition to the standard dopaminergic therapy, leads to significant improvements in bradykinesia during clinically relevant periods associated with peripheral L-DOPA dynamics, i.e., the OFF state in the morning, delayed-ON, and wearing-OFF periods.
Subject(s)
Oxadiazoles , Parkinson Disease , Humans , Parkinson Disease/complications , Parkinson Disease/drug therapy , Levodopa/adverse effects , Antiparkinson Agents/therapeutic use , Hypokinesia/drug therapy , Hypokinesia/etiology , Biomechanical Phenomena , Catechol O-Methyltransferase Inhibitors/pharmacology , Catechol O-Methyltransferase Inhibitors/therapeutic useABSTRACT
Seawater warming and marine heatwaves (MHWs) have a major role on the fragmentation and loss of coastal marine habitats. Understanding the resilience and potential for adaptation of marine habitat forming species to ocean warming becomes pivotal for predicting future changes, improving present conservation and restoration strategies. In this study, a thermo-tolerance experiment was conducted to investigate the physiological effects of short vs long MHWs occurring at different timing on recruits of Gongolaria barbata, a canopy-forming species widespread in the Mediterranean Sea. The recruits were collected from a population of the Marine Protected Area of Porto Cesareo (Apulia, Ionian Sea). Recruits length, PSII maximal photochemical efficiency (Fv/Fm), photosynthetic pigments content, concentrations of antioxidant compounds and total antioxidant activity (DPPH) were the response variables measured during the experiment. Univariate asymmetrical analyses highlighted that all physiological variables were significantly affected by both the duration and the timing of the thermal stress with the only exception of recruits length. The higher Fv/Fm ratio, chlorophylls and carotenoids content, and antioxidant compounds concentration in recruits exposed to long-term stress likely indicate an acclimation of thalli to the new environmental conditions and hence, an increased tolerance of G. barbata to thermal stress. Results also suggest that the mechanisms of adaptation activated in response to thermal stress did not affect the natural growth rate of recruits. Overall, this study supports the hypothesis that canopy-forming species can adapt to future climate conditions demonstrating a physiological acclimation to cope with MHWs, providing strong evidence that adaptation of marine species to thermal stress is more frequent than expected, this contributing to design tailored conservation and restoration strategies for marine coastal habitat.
Subject(s)
Seaweed , Antioxidants , Seawater , Ecosystem , Mediterranean Sea , Climate ChangeABSTRACT
INTRODUCTION: In this research, our primary objective was to explore the correlation between basal ganglia dopaminergic neurotransmission, assessed using 123I-FP-CIT (DAT-SPECT), and finger movements abnormalities in patients with essential tremor (ET) and Parkinson's disease (PD). METHODS: We enrolled 16 patients with ET, 17 with PD, and 18 healthy controls (HC). Each participant underwent comprehensive clinical evaluations, kinematic assessments of finger tapping. ET and PD patients underwent DAT-SPECT imaging. The DAT-SPECT scans were subjected to both visual and semi-quantitative analysis using DaTQUANT®. We then investigated the correlations between the clinical, kinematic, and DAT-SPECT data, in patients. RESULTS: Our findings confirm that individuals with ET exhibited slower finger tapping than HC. Visual evaluation of radiotracer uptake in both striata demonstrated normal levels within the ET patient cohort, while PD patients displayed reduced uptake. However, there was notable heterogeneity in the quantification of uptake within the striata among ET patients. Additionally, we found a correlation between the amount of radiotracer uptake in the striatum and movement velocity during finger tapping in patients. Specifically, lower radioligand uptake corresponded to decreased movement velocity (ET: coef. = 0.53, p-adj = 0.03; PD: coef. = 0.59, p-adj = 0.01). CONCLUSION: The study's findings suggest a potential link between subtle changes in central dopaminergic tone and altered voluntary movement execution, in ET. These results provide further insights into the pathophysiology of ET. However, longitudinal studies are essential to determine whether the slight reduction in dopaminergic tone observed in ET patients represents a distinct subtype of the disease or could serve as a predictor for the clinical progression into PD.
Subject(s)
Essential Tremor , Parkinson Disease , Humans , Essential Tremor/diagnostic imaging , Hypokinesia/diagnostic imaging , Hypokinesia/etiology , Parkinson Disease/diagnostic imaging , Tomography, Emission-Computed, Single-Photon/methods , Corpus Striatum , Dopamine Plasma Membrane Transport Proteins/metabolismABSTRACT
BACKGROUND: Bradykinesia is the hallmark feature of Parkinson's disease (PD); however, it can manifest in other conditions, including essential tremor (ET), and in healthy elderly individuals. OBJECTIVE: Here we assessed whether bradykinesia features aid in distinguishing PD, ET, and healthy elderly individuals. METHODS: We conducted simultaneous video and kinematic recordings of finger tapping in 44 PD patients, 69 ET patients, and 77 healthy elderly individuals. Videos were evaluated blindly by expert neurologists. Kinematic recordings were blindly analyzed. We calculated the inter-raters agreement and compared data among groups. Density plots assessed the overlapping in the distribution of kinematic data. Regression analyses and receiver operating characteristic curves determined how the kinematics influenced the likelihood of belonging to a clinical score category and diagnostic group. RESULTS: The inter-rater agreement was fair (Fleiss Kâ=â0.32). Rater found the highest clinical scores in PD, and higher scores in ET than healthy elderly individuals (pâ<â0.001). In regard to kinematic analysis, the groups showed variations in movement velocity, with PD presenting the slowest values and ET displaying less velocity than healthy elderly individuals (all psâ<â0.001). Additionally, PD patients showed irregular rhythm and sequence effect. However, kinematic data significantly overlapped. Regression analyses showed that kinematic analysis had high specificity in differentiating between PD and healthy elderly individuals. Nonetheless, accuracy decreased when evaluating subjects with intermediate kinematic values, i.e., ET patients. CONCLUSION: Despite a considerable degree of overlap, bradykinesia features vary to some extent in PD, ET, and healthy elderly individuals. Our findings have implications for defining bradykinesia and categorizing patients.
Subject(s)
Essential Tremor , Parkinson Disease , Humans , Aged , Parkinson Disease/complications , Parkinson Disease/diagnosis , Hypokinesia/diagnosis , Hypokinesia/etiology , Essential Tremor/diagnosis , Movement , Biomechanical PhenomenaABSTRACT
Patients with Parkinson's disease (PD) show impaired short-term potentiation (STP) mechanisms in the primary motor cortex (M1). However, the role played by this neurophysiological abnormality in bradykinesia pathophysiology is unknown. In this study, we used a multimodal neuromodulation approach to test whether defective STP contributes to bradykinesia. We evaluated STP by measuring motor-evoked potential facilitation during 5 Hz-repetitive transcranial magnetic stimulation (rTMS) and assessed repetitive finger tapping movements through kinematic techniques. Also, we used transcranial alternating current stimulation (tACS) to drive M1 oscillations and experimentally modulate bradykinesia. STP was assessed during tACS delivered at beta (ß) and gamma (γ) frequency, and during sham-tACS. Data were compared to those recorded in a group of healthy subjects. In PD, we found that STP was impaired during sham- and γ-tACS, while it was restored during ß-tACS. Importantly, the degree of STP impairment was associated with the severity of movement slowness and amplitude reduction. Moreover, ß-tACS-related improvements in STP were linked to changes in movement slowness and intracortical GABA-A-ergic inhibition during stimulation, as assessed by short-interval intracortical inhibition (SICI). Patients with prominent STP amelioration had greater SICI reduction (cortical disinhibition) and less slowness worsening during ß-tACS. Dopaminergic medications did not modify ß-tACS effects. These data demonstrate that abnormal STP processes are involved in bradykinesia pathophysiology and return to normal levels when ß oscillations increase. STP changes are likely mediated by modifications in GABA-A-ergic intracortical circuits and may represent a compensatory mechanism against ß-induced bradykinesia in PD.
Subject(s)
Motor Cortex , Parkinson Disease , Humans , Parkinson Disease/complications , Parkinson Disease/therapy , Hypokinesia/etiology , Transcranial Magnetic Stimulation/methods , Evoked Potentials, Motor , gamma-Aminobutyric AcidABSTRACT
The "interlimb transfer" phenomenon consists of improved performance of the trained and untrained contralateral limbs after unilateral motor practice. We here assessed whether a visuomotor learning task can be transferred from one hemisphere to the other, whether this occurs symmetrically, and the cortical neurophysiological correlates of this phenomenon, focusing on interhemispheric connectivity measures. We enrolled 33 healthy subjects (age range: 24-73 years). Participants underwent two randomized sessions, which investigated the transfer from the dominant to the nondominant hand and vice versa. Measures of cortical and intracortical excitability and interhemispheric inhibition were assessed through transcranial magnetic stimulation before and after a visuomotor task. The execution of the visuomotor task led to an improvement in motor performance with the dominant and nondominant hands and induced a decrease in intracortical inhibition in the trained hemisphere. Participants were also able to transfer the visuomotor learned skill. The interlimb transfer, however, only occurred from the dominant to the nondominant hand and positively correlated with individual learning-related changes in interhemispheric inhibition. We here demonstrated that the "interlimb transfer" of a visuomotor task occurs asymmetrically and relates to the modulation of specific inhibitory interhemispheric connections. The study results have pathophysiological, clinical, and neuro-rehabilitative implications.
Subject(s)
Functional Laterality , Learning , Humans , Young Adult , Adult , Middle Aged , Aged , Functional Laterality/physiology , Learning/physiology , Inhibition, Psychological , Hand/physiology , Psychomotor Performance/physiology , Motor Skills/physiologyABSTRACT
BACKGROUND AND PURPOSE: Essential tremor (ET) is a common and heterogeneous disorder characterized by postural/kinetic tremor of the upper limbs and other body segments and by non-motor symptoms, including cognitive and psychiatric abnormalities. Only a limited number of longitudinal studies have comprehensively and simultaneously investigated motor and non-motor symptom progression in ET. Possible soft signs that configure the ET-plus diagnosis are also under-investigated in follow-up studies. We aimed to longitudinally investigate the progression of ET manifestations by means of clinical and neurophysiological evaluation. METHODS: Thirty-seven ET patients underwent evaluation at baseline (T0) and at follow-up (T1; mean interval ± SD = 39.89 ± 9.83 months). The assessment included the clinical and kinematic evaluation of tremor and voluntary movement execution, as well as the investigation of cognitive and psychiatric disorders. RESULTS: A higher percentage of patients showed tremor in multiple body segments and rest tremor at T1 as compared to T0 (all p-values < 0.01). At T1, the kinematic analysis revealed reduced finger-tapping movement amplitude and velocity as compared to T0 (both p-values < 0.001). The prevalence of cognitive and psychiatric disorders did not change between T0 and T1. Female sex, absence of family history, and rest tremor at baseline were identified as predictive factors of worse disease progression. CONCLUSIONS: ET progression is characterized by the spread of tremor in multiple body segments and by the emergence of soft signs. We also identified possible predictors of disease worsening. The results contribute to a better understanding of ET classification and pathophysiology.
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Essential Tremor , Mental Disorders , Humans , Female , Essential Tremor/diagnosis , Tremor/diagnosis , Longitudinal Studies , Upper ExtremityABSTRACT
Petroleum hydrocarbons and heavy metals are some of the most widespread contaminants affecting marine ecosystems, urgently needing effective and sustainable remediation solutions. Microbial-based bioremediation is gaining increasing interest as an effective, economically and environmentally sustainable strategy. Here, we hypothesized that the heavily polluted coastal area facing the Sarno River mouth, which discharges >3 tons of polycyclic aromatic hydrocarbons (PAHs) and â¼15 tons of heavy metals (HMs) into the sea annually, hosts unique microbiomes including marine bacteria useful for PAHs and HMs bioremediation. We thus enriched the microbiome of marine sediments, contextually selecting for HM-resistant bacteria. The enriched mixed bacterial culture was subjected to whole-DNA sequencing, metagenome-assembled-genomes (MAGs) annotation, and further sub-culturing to obtain the major bacterial species as pure strains. We obtained two novel isolates corresponding to the two most abundant MAGs (Alcanivorax xenomutans strain-SRM1 and Halomonas alkaliantarctica strain-SRM2), and tested their ability to degrade PAHs and remove HMs. Both strains exhibited high PAHs degradation (60-100%) and HMs removal (21-100%) yield, and we described in detail >60 genes in their MAGs to unveil the possible genetic basis for such abilities. Most promising yields (â¼100%) were obtained towards naphthalene, pyrene and lead. We propose these novel bacterial strains and related genetic repertoire to be further exploited for effective bioremediation of marine environments contaminated with both PAHs and HMs.