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1.
J Neurol ; 271(7): 4039-4045, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38568225

ABSTRACT

INTRODUCTION: Cladribine is an oral immune reconstitution therapy for relapsing multiple sclerosis (RMS). Hormonal and immune changes are responsible for the decline of disease activity in the third trimester of pregnancy and disease reactivation in the early post-partum period.We investigate the impact of pregnancy on disease activity in women with MS who conceived after cladribine treatment. METHODS: We recruited women of childbearing age with relapsing-remitting MS (RRMS) who became pregnant or not after being treated with cladribine. For both groups, demographic, clinical and radiological data were collected 1 year before and after treatment during a mean follow-up of 3.53 years. We compared disease activity over time between groups using variance analysis for repeated measures. RESULTS: 48 childbearing women were included. 25 women had a pregnancy after a mean of 1.75 years from the first treatment cycle. Women with or without pregnancy did not differ in demographics or pre-cladribine disease activity. No significant differences in disease activity or EDSS worsening were found between women with or without pregnancy. DISCUSSION: Our findings suggest that pregnancy does not appear to influence disease activity and disability in women previously treated with cladribine; further studies with larger numbers and longer follow-up are needed to confirm this finding.


Subject(s)
Cladribine , Immunosuppressive Agents , Multiple Sclerosis, Relapsing-Remitting , Humans , Female , Cladribine/pharmacology , Cladribine/administration & dosage , Pregnancy , Adult , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Immunosuppressive Agents/therapeutic use , Pregnancy Complications/drug therapy , Follow-Up Studies , Young Adult , Disability Evaluation
2.
Mult Scler Relat Disord ; 78: 104907, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37523809

ABSTRACT

BACKGROUND: Although multiple sclerosis (MS) Intimacy and Sexuality Questionnaire-19 (MSISQ-19) is a widely applied tool, no unique definition of sexual dysfunction (SD) based on its score exists. OBJECTIVE: To explore the impact of different MSISQ-19 cut-offs on SD prevalence and associated risk factors, providing relevant information for its application in research and clinical settings. METHODS: After defining SD according to two different MSISQ-19 cut-offs in 1155 people with MS (pwMS), we evaluated SD prevalence and association with sociodemographic and clinical features, mood status and disability via logistic regression. RESULTS: Depending on the chosen cut-off, 45% to 54% of pwMS reported SD. SD defined as MSISQ-19 score >30 was predicted by age (OR=1.01, p=0.047), cognition (OR=0.96, p=0.004) and anxiety (OR=1.03, p=0.019). SD defined as a score >3 on any MSISQ-19 item was predicted by motor disability (OR=1.12, p=0.003) and cognition (OR= 0.96, p=0.002). CONCLUSION: Applying different MSISQ-19 cut-offs influences both the estimated prevalence and the identification of risk factors for SD, a finding that should be considered during study planning and data interpretation. Preserved cognition exerts a protective effect towards SD regardless from the specific study setting, representing a key point for the implementation of preventive and therapeutic strategies.

3.
Prev Sci ; 24(Suppl 1): 30-39, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37261635

ABSTRACT

Substance use disorder prevention programs are most effective when matched appropriately to the baseline risk of the population. Individuals who misuse opioids often have unique risk profiles different from those who use other substances such as alcohol or cannabis. However, most substance use prevention programs are geared toward universal audiences, neglecting key inflection points along the continuum of care. The HEAL Prevention Cooperative (HPC) is a unique cohort of research projects that represents a continuum of care, from community-level universal prevention to indicated prevention among older adolescents and young adults who are currently misusing opioids or other substances. This paper describes the theoretical basis for addressing opioid misuse and opioid use disorder across the prevention continuum, using examples from research projects in the HPC.


Subject(s)
Cannabis , Opioid-Related Disorders , Prescription Drug Misuse , Adolescent , Young Adult , Humans , Opioid-Related Disorders/prevention & control , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/epidemiology , Analgesics, Opioid/therapeutic use , Continuity of Patient Care
4.
J Hydrol (Amst) ; 620(A)2023 May 01.
Article in English | MEDLINE | ID: mdl-39211483

ABSTRACT

The hillslope and channel dynamics that govern streamflow permanence in headwater systems have important implications for ecosystem functioning and downstream water quality. Recent advancements in process-based, semi-distributed hydrologic models that build upon empirical studies of streamflow permanence in well-monitored headwater catchments show promise for characterizing the dynamics of streamflow permanence in headwater systems. However, few process-based models consider the continuum of hillslope-stream network connectivity as a control on streamflow permanence in headwater systems. The objective of this study was to expand a process-based, catchment-scale hydrologic model to better understand the spatiotemporal dynamics of headwater streamflow permanence and to identify controls of streamflow expansion and contraction in a headwater network. Further, we aimed to develop an approach that enhanced the fidelity of model simulations, yet required little additional data, with the intent that the model might be later transferred to catchments with limited long-term and spatially explicit measurements. This approach facilitated network-scale estimates of the controls of streamflow expansion and contraction, albeit with higher degrees of uncertainty in individual reaches due to data constraints. Our model simulated that streamflow permanence was highly dynamic in first-order reaches with steep slopes and variable contributing areas. The simulated stream network length ranged from nearly 98±2% of the geomorphic channel extent during wet periods to nearly 50±10% during dry periods. The model identified a discharge threshold of approximately 1 mm d-1, above which the rate of streamflow expansion decreases by nearly an order of magnitude, indicating a lack of sensitivity of streamflow expansion to hydrologic forcing during high-flow periods. Overall, we demonstrate that process-based, catchment-scale models offer important insights on the controls of streamflow permanence, despite uncertainties and limitations of the model. We encourage researchers to increase data collection efforts and develop benchmarks to better evaluate such models.

5.
Sci Rep ; 12(1): 2449, 2022 02 14.
Article in English | MEDLINE | ID: mdl-35165360

ABSTRACT

Resting state fMRI has been employed to identify alterations in functional connectivity within or between brain regions following acute and chronic exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive component in cannabis. Most studies focused a priori on a limited number of local brain areas or circuits, without considering the impact of cannabis on whole-brain network organization. The present study attempted to identify changes in the whole-brain human functional connectome as assessed with ultra-high field (7T) resting state scans of cannabis users (N = 26) during placebo and following vaporization of cannabis. Two distinct data-driven methodologies, i.e. network-based statistics (NBS) and connICA, were used to identify changes in functional connectomes associated with acute cannabis intoxication and history of cannabis use. Both methodologies revealed a broad state of hyperconnectivity within the entire range of major brain networks in chronic cannabis users compared to occasional cannabis users, which might be reflective of an adaptive network reorganization following prolonged cannabis exposure. The connICA methodology also extracted a distinct spatial connectivity pattern of hypoconnectivity involving the dorsal attention, limbic, subcortical and cerebellum networks and of hyperconnectivity between the default mode and ventral attention network, that was associated with the feeling of subjective high during THC intoxication. Whole-brain network approaches identified spatial patterns in functional brain connectomes that distinguished acute from chronic cannabis use, and offer an important utility for probing the interplay between short and long-term alterations in functional brain dynamics when progressing from occasional to chronic use of cannabis.


Subject(s)
Brain/diagnostic imaging , Brain/physiopathology , Cannabis/chemistry , Connectome/methods , Dronabinol/administration & dosage , Marijuana Smoking/physiopathology , Marijuana Smoking/psychology , Plant Extracts/administration & dosage , Psychotropic Drugs/administration & dosage , Adult , Attention/drug effects , Cognition/drug effects , Cross-Over Studies , Double-Blind Method , Emotions/drug effects , Female , Humans , Magnetic Resonance Imaging/methods , Male , Young Adult
6.
Neurobiol Dis ; 143: 105009, 2020 09.
Article in English | MEDLINE | ID: mdl-32634578

ABSTRACT

Emerging evidence indicates that Huntington's disease (HD) may be described as multi-organ pathology. In this context, we and others have contributed to demonstrate that the disease is characterized by an impairment of the homeostasis of gastro-intestinal (GI) tract. Sphingolipids represent a class of molecules involved in the regulation and maintenance of different tissues and organs including GI system. In this study, we investigated whether the alteration of Sphingosine-1-phosphate (S1P) metabolism, previously described in human HD brains and animal models, is also detectable peripherally in R6/2 HD mice. Our findings indicate, for the first time, that sphingolipid metabolism is perturbed early in the disease in the intestinal tract of HD mice and, its modulation by K6PC-5, a selective activator of S1P synthesis, preserved intestinal integrity and homeostasis. These results further support the evidence that modulation of sphingolipid pathways may represent a potential therapeutic option in HD and suggest that it has also the potential to counteract the peripheral disturbances which may usually complicate the management of the disease and affect patient's quality of life.


Subject(s)
Amides/pharmacology , Huntington Disease/metabolism , Intestines/drug effects , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Animals , Disease Models, Animal , Homeostasis/drug effects , Lysophospholipids/metabolism , Mice , Phosphotransferases (Alcohol Group Acceptor)/drug effects , Sphingolipids/metabolism , Sphingosine/analogs & derivatives , Sphingosine/metabolism
7.
Neurol Sci ; 41(5): 1075-1079, 2020 May.
Article in English | MEDLINE | ID: mdl-31863327

ABSTRACT

INTRODUCTION: Multiple sclerosis (MS) refers to chronic inflammation of the central nervous system including the brain and spinal cord. Dysphagia is a symptom that represents challenges in clinical practice. The aim of the present study was to evaluate the prevalence of dysphagia in an Italian cohort of subjects with MS using the Dysphagia Outcome Severity Score (DOSS), based on fibre-optic endoscopy, and determine factors that correlate with the presence of swallowing problems. MATHERIALS AND METHODS: Data were collected in a multicentre study from a consecutive sample of MS patients, irrespective of self-reported dysphagia. The study included 215 subjects. Possible scores for DOSS range from 7 to 1, with 7 indicating normal swallowing. RESULTS: One hundred twenty-four (57.7%) subjects demonstrated abnormal swallowing and 57 (26.5%) of these had swallowing problems that required nutrition/diet modifications when evaluated objectively with fibre-optic endoscopy. Subjects with dysphagia were more severely disabled and more often had a progressive form of MS, compared to MS subjects with normal swallowing. In subjects with EDSS, < 4, 8 (13.3%), had a DOSS < 4. Seventy-five percent of subjects older than 60 years of age had dysphagia. CONCLUSION: In this sample of MS patients, more nearly 60% showed swallowing problems.


Subject(s)
Deglutition Disorders/diagnosis , Deglutition Disorders/epidemiology , Multiple Sclerosis/epidemiology , Cohort Studies , Deglutition Disorders/complications , Endoscopy/methods , Female , Humans , Italy/epidemiology , Male , Middle Aged , Multiple Sclerosis/complications , Optical Fibers , Prevalence , Severity of Illness Index
8.
Hum Mol Genet ; 28(23): 4012-4021, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31630202

ABSTRACT

Huntington's disease (HD) has traditionally been described as a disorder purely of the brain; however, evidence indicates that peripheral abnormalities are also commonly seen. Among others, severe unintended body weight loss represents a prevalent and often debilitating feature of HD pathology, with no therapies available. It correlates with disease progression and significantly affects the quality of life of HD patients. Curcumin, a naturally occurring polyphenol with multiple therapeutic properties, has been validated to exert important beneficial effects under health conditions as well as in different pathological settings, including neurodegenerative and gastrointestinal (GI) disorders. Here, we investigated the potential therapeutic action that curcumin-supplemented diet may exert on central and peripheral dysfunctions in R6/2 mice, a well-characterized HD animal model which recapitulates some features of human pathology. Maintenance of normal motor function, protection from neuropathology and from GI dysfunction and preservation of GI emptying and conserved intestinal contractility, proved the beneficial role of life-long dietary curcumin in HD and corroborated the potential of the compound to be exploited to alleviate very debilitating symptoms associated with the disease.


Subject(s)
Behavior, Animal/drug effects , Curcumin/administration & dosage , Huntington Disease/diet therapy , Weight Loss/drug effects , Animals , Brain-Derived Neurotrophic Factor/metabolism , Curcumin/pharmacology , Dietary Supplements , Disease Models, Animal , Female , Huntington Disease/physiopathology , Male , Mice , Mice, Transgenic , Motor Activity/drug effects , Phenotype
9.
Eur Rev Med Pharmacol Sci ; 23(1): 389-396, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30657581

ABSTRACT

OBJECTIVE: The purpose of this study is to evaluate the haemodynamic and respiratory effects of dexmedetomidine vs. propofol in patients with OSAHS during the drug-induced sleep endoscopy (DISE), and analyze simultaneously the electromyography of genioglossus muscle. PATIENTS AND METHODS: We conducted a study on 50 patients with OSAHS; patients were subjected to DISE with simultaneous polygraphic cardiorespiratory measurement and electromyography of genioglossus muscle. Patients undergoing DISE were divided in two groups: in Group A (19 M; 8 W) was administered propofol TCI and in Group B (16 M; 7 W) was administered dexmedetomidine TCI. RESULTS: In Group A, a mean minimal SpO2 decreasing of 3.7% (p=0.000) and a mean SpO2 decreasing of 1.6% (p 0.001) was noticed, while there was an increase in BP20 of 14.8% (p=0.000) and HR20 of 11.1% (p=0.000). In Group B, it was showed a decreasing of mean minimal SpO2 and mean SpO2 values, about 1.8% (p=0.000) and 1.1% (p 0.009) respectively, while there was an increase of BP20 and HR20, about 8.7% (p=0.000) and 8% (p 0.002), respectively. Despite EMG activity comparing spontaneous sleep with propofol-DISE, there is a statistically significative change for the amplitude (p=0.040) and an increase of 7.01% for the area under the curve (AUC). Comparing spontaneous sleep with dexmedetomidine-DISE induced one, there is only an increase of 25.87% in the AUC. CONCLUSIONS: A greater worsening of the cardio-respiratory basal values was noted after sleep induction with Propofol and same results were obtained confronting EMG of genioglossus muscle data.


Subject(s)
Endoscopy/methods , Hypnotics and Sedatives/adverse effects , Muscle, Skeletal/drug effects , Polysomnography/methods , Sleep Apnea, Obstructive/diagnosis , Adult , Aged , Dexmedetomidine/administration & dosage , Dexmedetomidine/adverse effects , Electromyography , Female , Humans , Hypnotics and Sedatives/administration & dosage , Male , Middle Aged , Muscle Strength/drug effects , Muscle Strength/physiology , Muscle, Skeletal/physiopathology , Propofol/administration & dosage , Propofol/adverse effects , Prospective Studies , Respiration/drug effects , Tongue , Treatment Outcome
10.
J Neurol ; 266(2): 411-416, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30515629

ABSTRACT

BACKGROUND: Teriflunomide (TRF) and Dimethyl fumarate (DMF) are licensed drugs for relapsing-remitting Multiple Sclerosis (RRMS). OBJECTIVES: We aimed to compare the rate and the time to discontinuation among persons with RRMS (pwRRMS), newly treated with TRF and DMF. MATERIALS AND METHODS: A retrospective study on prospectively collected data was performed in nine tertiary MS centers, in Italy. The 24-month discontinuation rate in the two cohorts was the primary study outcome. We also assessed the time to discontinuation and reasons of therapy withdrawn. Discontinuation of TRF and DMF was defined as a gap of treatment ≥ 60 days. RESULTS: A cohort of 903 pwRRMS (316 on TRF and 587 on DMF) was analyzed. During 24 months of follow-up, pwRRMS on TRF and DMF showed similar discontinuation rates. The analysis of predictors with Cox regression model showed differences between the two groups (p for log-rank test = 0.007); male gender [HR 2.21 (1.00-4.90); p = 0.01] and the number of previous switches [HR 1.47 (1.16-1.86); p = 0.01] were associated with higher hazard of discontinuation in the DMF group. CONCLUSIONS: In a real-world setting, pwRRMS on TRF and DMF had similar discontinuation rates over 24 months. Male pwRRMS on DMF with a previous history of therapeutic failure are at more risk of discontinuation therapy.


Subject(s)
Crotonates/administration & dosage , Dimethyl Fumarate/administration & dosage , Immunosuppressive Agents/administration & dosage , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Toluidines/administration & dosage , Adult , Follow-Up Studies , Humans , Hydroxybutyrates , Italy , Middle Aged , Nitriles , Retrospective Studies , Time Factors
11.
Eur J Neurol ; 25(12): 1425-1431, 2018 12.
Article in English | MEDLINE | ID: mdl-29956427

ABSTRACT

BACKGROUND AND PURPOSE: Late-onset multiple sclerosis (MS) has a prevalence of about 10-20% in natural history MS studies. Few data have been published about the long-term disease trajectory in the cohort of late-onset relapsing-remitting MS (LORRMS). The aim of this study was to identify the risk factors for reaching an Expanded Disability Status Scale (EDSS) score of 6.0 in LORRMS (onset at >40 years of age) and young-onset relapsing-remitting MS (YORRMS) (onset between 18 and 40 years of age). METHODS: Clinical and radiological [magnetic resonance imaging (MRI) of the brain] follow-up data were collected. Disability was assessed by EDSS score. A Cox proportional hazards model was used to evaluate the demographic and clinical predictors of reaching an EDSS score of 6.0 in the two cohorts. RESULTS: A total of 671 patients with relapsing-remitting MS were enrolled, 143 (21.3%) with LORRMS and 528 (78.7%) with YORRMS. In LORRMS, age at onset was 47.8 ± 5.3 (mean ± SD) years and duration of follow-up was 120.7 ± 52.7 months. In YORRMS, age at onset was 27 ± 2.7 years and duration of follow-up was 149.9 ± 92.7 months. The survival curve analyses showed a higher probability of reaching an EDSS score of 6.0 for LORRMS in a shorter time (months) than for YORRMS (94.2 vs. 103.2 months; log-rank 8.8; P < 0.05). On MRI, YORRMS showed more brain inflammatory features than LORRMS. In the multivariate Cox model, age at onset [Exp(B) value, 6.5; 95% confidence interval, 1.9-22.6; P < 0.001] and male gender [Exp(B) value, 1.7; 95% confidence interval, 1.0-2.8; P < 0.05] were the strongest predictors of reaching an EDSS score of 6.0. CONCLUSIONS: The male population with LORRMS reached severe disability faster than those with YORRMS, even when YORRMS showed more brain inflammatory features on MRI.


Subject(s)
Brain/diagnostic imaging , Multiple Sclerosis, Relapsing-Remitting/diagnosis , Adolescent , Adult , Age of Onset , Disability Evaluation , Disease Progression , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , Retrospective Studies , Risk Factors , Young Adult
12.
Expert Rev Clin Pharmacol ; 11(5): 531-536, 2018 May.
Article in English | MEDLINE | ID: mdl-29521113

ABSTRACT

BACKGROUND: The efficacy of lateral and escalation switch is a challenge in MS. We compared in a real-world setting the efficacy of switching to IFN beta-1a 44 mcg or to fingolimod in persons with relapsing remitting MS (pwRRMS) who failed with others injectable IFNs or glatiramer acetate. RESEARCH DESIGN AND METHODS: retrospective analysis of 24 months prospectively-collected data at the MS center of the University of Catania, Italy was performed. Patients who were switched to IFN-beta 1a 44 mcg or fingolimod were analyzed using propensity-score covariate adjustment model within demographic (e.g. age and gender) and disease (e.g. timing of pre-switch relapse) characteristics. Switching-time was considered the starting-time of the observation. RESULTS: 43 pwRRMS on IFN beta-1a 44 mcg and 49 pwRRMS on fingolimod were included. Baseline characteristics differed for EDSS score and number of T2 lesions (higher in group on fingolimod). At 24 months of follow up, both groups showed no differences in the survival curves of reaching a first new relapse, new T2 and Gd+ MRI brain lesions, even corrected for the propensity score covariate adjustment. CONCLUSIONS: lateral switch to IFN beta-1a 44 mcg and escalation switch to fingolimod showed same ability in influencing RRMS disease activity at 24 months.


Subject(s)
Fingolimod Hydrochloride/administration & dosage , Immunologic Factors/administration & dosage , Interferon beta-1a/administration & dosage , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Adult , Drug Substitution , Female , Follow-Up Studies , Humans , Immunosuppressive Agents/administration & dosage , Male , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Retrospective Studies , Treatment Outcome , Young Adult
13.
J Neurol ; 265(4): 828-835, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29404736

ABSTRACT

BACKGROUND: Pain is a common and heterogeneous complication of multiple sclerosis (MS). In this multicenter, cross sectional study, we aimed at investigating the prevalence of pain in MS using highly specific criteria for distinguishing the different types of pain. MATERIALS AND METHODS: After a structured interview, in patients with pain, clinical examination and DN4 questionnaire were used for distinguishing neuropathic and nociceptive pain. In subjects with neuropathic pain, the Neuropathic Pain Symptom Inventory was used for differentiating neuropathic pain symptoms. RESULTS: We enrolled 1249 participants (832 F, 417 M, mean age 33.9 years, mean disease duration 8 years, mean EDSS 3.2); based on clinical evaluation and DN4 score 429 patients (34.34%) were classified with pain (470 pain syndromes): 286 nociceptive pain syndromes and 184 neuropathic pain syndromes. Multivariate analysis showed that pain was associated with age, gender and disease severity and that neuropathic pain was distinctly associated with EDSS. CONCLUSIONS: Our study, providing definite information on the prevalence, characteristics and variables associated with neuropathic pain due to MS, shows that a more severe disease course is associated with a higher risk of neuropathic pain. Our findings might, therefore, provide a basis for improving the clinical management of this common MS complication.


Subject(s)
Multiple Sclerosis/complications , Neuralgia/diagnosis , Neuralgia/etiology , Pain Measurement/methods , Adult , Cross-Sectional Studies , Disability Evaluation , Female , Humans , Italy , Male , Middle Aged , Neuralgia/therapy , Surveys and Questionnaires , Young Adult
14.
Thromb Res ; 159: 100-108, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29078099

ABSTRACT

Neuromedin U (NmU) is a pleiotropic hypothalamic neuropeptide involved in the gut-brain axis. It acts via both a Gαq/11-coupled receptor (NMUR1) and a Gαi-coupled receptor (NMUR2) in different cell types. Expression of both receptors was reported in platelets, but their significance for NmU signaling remains elusive. We studied the potential effects of NmU on human platelet activation. In platelet-rich plasma (PRP), NmU alone (up to 10µM) did not induce any measurable aggregation, but at nanomolar concentrations, it potentiated platelet aggregation by low (mean 0.47µM) ADP concentrations (from 25.9±3.6% to 74.8±2.7% maximal aggregation for ADP vs. ADP+NmU, 100nM, mean±SEM, n=13), accompanied by platelet P-selectin expression and intracellular calcium mobilization. Accordingly, platelet preincubation with NmU for 2min sensitized platelets for subsequent activation by ADP. When P2Y1 was inactivated by 50µM MRS2179, NmU comparably potentiated ADP-induced PRP aggregation, suggestive of cooperative activation with Gαi-coupled P2Y12. Likewise, NmU potentiated platelet aggregation by Gαi-operated epinephrine at subthreshold concentrations (99ng/ml, mean), but not that by Gαq-dependent serotonin (20µM). Platelet aggregation by NmU/epinephrine combination was fully inhibited by the Gαq inhibitor YM-254890 (1µM). qPCR detection and western blot analysis substantiated platelet expression of NMUR1 in different donors, a finding collectively complying with functionally relevant Gαq/11-mediated activation of platelet NMUR1 by NmU. Our findings advocate further studies on platelet sensitization by NmU, released during vascular activation and injury, to define its role as a modifier of platelet responsiveness to the physiological activation signals, operational in cardiovascular health and disease.


Subject(s)
Neuropeptides/therapeutic use , Platelet Activation/drug effects , Humans , Neuropeptides/pharmacology , Signal Transduction
15.
IEEE Int Conf Rehabil Robot ; 2017: 56-61, 2017 07.
Article in English | MEDLINE | ID: mdl-28813793

ABSTRACT

The combined use of Functional Electrical Stimulation (FES) and robotic technologies is advocated to improve rehabilitation outcomes after stroke. This work describes an arm rehabilitation system developed within the European project RETRAINER. The system consists of a passive 4-degrees-of-freedom exoskeleton equipped with springs to provide gravity compensation and electromagnetic brakes to hold target positions. FES is integrated in the system to provide additional support to the most impaired muscles. FES is triggered based on the volitional EMG signal of the same stimulated muscle; in order to encourage the active involvement of the patient the volitional EMG is also monitored throughout the task execution and based on it a happy or sad emoji is visualized at the end of each task. The control interface control of the system provides a GUI and multiple software tools to organize rehabilitation exercises and monitor rehabilitation progress. The functionality and the usability of the system was evaluated on four stroke patients. All patients were able to use the system and judged positively its wearability and the provided support. They were able to trigger the stimulation based on their residual muscle activity and provided different levels of active involvement in the exercise, in agreement with their level of impairment. A randomized controlled trial aimed at evaluating the effectiveness of the RETRAINER system to improve arm function after stroke is currently ongoing.


Subject(s)
Electromyography , Exoskeleton Device , Neural Prostheses , Stroke Rehabilitation , Upper Extremity/physiology , Adult , Electromyography/instrumentation , Electromyography/methods , Equipment Design , Female , Humans , Male , Middle Aged , Pilot Projects , Software , Stroke Rehabilitation/instrumentation , Stroke Rehabilitation/methods , Task Performance and Analysis
16.
Haemophilia ; 23(4): 538-546, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28574179

ABSTRACT

PATIENTS AND METHODS: A longitudinal study was carried out in 255 children from 10 centres in nine developing countries over 5 years to assess the musculoskeletal outcome of children on episodic factor replacement. Outcome was documented by assessment of the annual joint bleeding rate (AJBR), WFH clinical and Pettersson radiological joint scores as well as the FISH score for activities. Of the 203 patients for whom data was available at the end of 5 years, 164 who had received only episodic treatment are included in this report. RESULTS: The median age at the beginning of the study was 10 years (IQR 7-12). The median clotting factor concentrate (CFC) usage was 662 IU kg-1 year-1 (IQ range: 280-1437). The median AJBR was 10 (IQ range: 5-17). The median AJBR was higher in the older children with the median being 5 for the 5 year old child, while it was 9 for the 10 year old and 11 for children older than 15. Given the episodic nature of the replacement therapy, those with a higher AJBR used significantly greater annual CFC doses (P < 0.001); The median change in WFH clinical score and Pettersson radiological score over the 5 years was 0.4/year for each, while the FISH deteriorated at a rate of 0.2/year with poor correlation of these changes with CFC dose. WFH and FISH scores were significantly worse in those with an AJBR of >3 per year (P = 0.001). The change in the Pettersson score was significantly more in those with an AJBR of >5 per year (P = 0.020). Significant changes in FISH scores were only noted after 10 years of age. CONCLUSION: Episodic CFC replacement over a large range of doses does not alter the natural course of bleeding in haemophilia or the musculoskeletal deterioration and should not be recommended as a long term option for treatment. Prophylaxis is the only way to preserve musculoskeletal function in haemophilia.


Subject(s)
Blood Coagulation Factors/pharmacology , Hemorrhage/prevention & control , Musculoskeletal System/drug effects , Adolescent , Child , Female , Humans , Longitudinal Studies , Male , Musculoskeletal System/pathology , Young Adult
17.
Chaos ; 27(4): 047407, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28456159

ABSTRACT

Dynamical models implemented on the large scale architecture of the human brain may shed light on how a function arises from the underlying structure. This is the case notably for simple abstract models, such as the Ising model. We compare the spin correlations of the Ising model and the empirical functional brain correlations, both at the single link level and at the modular level, and show that their match increases at the modular level in anesthesia, in line with recent results and theories. Moreover, we show that at the peak of the specific heat (the critical state), the spin correlations are minimally shaped by the underlying structural network, explaining how the best match between the structure and function is obtained at the onset of criticality, as previously observed. These findings confirm that brain dynamics under anesthesia shows a departure from criticality and could open the way to novel perspectives when the conserved magnetization is interpreted in terms of a homeostatic principle imposed to neural activity.


Subject(s)
Anesthesia , Connectome , Models, Neurological , Wakefulness/physiology , Brain/physiology , Humans
18.
Sci Rep ; 7: 42797, 2017 02 17.
Article in English | MEDLINE | ID: mdl-28211486

ABSTRACT

Whereas Huntington's disease (HD) is unequivocally a neurological disorder, a critical mass of emerging studies highlights the occurrence of peripheral pathology like cardiovascular defects in both animal models and humans. The overt impairment in cardiac function is normally expected to be associated with peripheral vascular dysfunction, however whether this assumption is reasonable or not in HD is still unknown. In this study we functionally characterized the vascular system in R6/2 mouse model (line 160 CAG), which recapitulates several features of human pathology including cardiac disease. Vascular reactivity in different arterial districts was determined by wire myography in symptomatic R6/2 mice and age-matched wild type (WT) littermates. Disease stage was assessed by using well-validated behavioural tests like rotarod and horizontal ladder task. Surprisingly, no signs of vascular dysfunction were detectable in symptomatic mice and no link with motor phenotype was found.


Subject(s)
Arteries/physiology , Huntingtin Protein/genetics , Huntington Disease/pathology , Muscle, Skeletal/physiopathology , Animals , Disease Models, Animal , Electromyography , Humans , Huntington Disease/genetics , Huntington Disease/physiopathology , Mice , Mice, Transgenic , Mutation , Phenotype , Vascular Capacitance
19.
J Am Water Resour Assoc ; 53(4): 774-790, 2017 Aug 02.
Article in English | MEDLINE | ID: mdl-33408455

ABSTRACT

Floodplain delineation may inform protection of wetland systems under local, state, or federal laws. Nationally available Federal Emergency Management Agency Flood Insurance Rate Maps (FIRMs, "100-year floodplain" maps) focus on urban areas and higher-order river systems, limiting utility at large scales. Few other national-scale floodplain data are available. We acquired FIRMs for a large watershed and compared FIRMs to floodplain and integrated wetland area mapping methods based on (1) geospatial distance, (2) geomorphic setting, and (3) soil characteristics. We used observed flooding events (OFEs) with recurrence intervals of 25-50 to >100 years to assess floodplain estimate accuracy. FIRMs accurately reflected floodplain areas based on OFEs and covered 32% of river length, whereas soil-based mapping was not as accurate as FIRMs but characterized floodplain areas over approximately 65% of stream length. Geomorphic approaches included more areas than indicated by OFE, whereas geospatial approaches tended to cover less area. Overall, soil-based methods have the highest utility in determining floodplains and their integrated wetland areas at large scales due to the use of nationally available data and flexibility for regional application. These findings will improve floodplain and integrated wetland system extent assessment for better management at local, state, and national scales.

20.
PLoS One ; 11(9): e0160261, 2016.
Article in English | MEDLINE | ID: mdl-27632167

ABSTRACT

BACKGROUND: Depression occurs in about 50% of patients with multiple sclerosis. The aims of this study was to investigate the prevalence of depressive symptoms in a multicenter MS population using the Beck Depression Inventory II (BDI II) and to identify possible correlations between the BDI II score and demographic and clinical variables. METHODS: Data were collected in a multi-center, cross-sectional study over a period of six months in six MS centers in Italy using BDI II. RESULTS: 1,011 MS patients participated in the study. 676 subjects were female, with a mean age of 34 years (SD 10.8), mean EDSS of 3.3 (0-8.5) and mean disease duration of 10.3 years (range 1-50 years). 668 (%) subjects scored lower than 14 on the BDI II and 343 (33.9%) scored greater than 14 (14 cut-off score). For patients with BDI>14 multivariate analysis showed a significant difference between EDSS and disease course. BDI II scores for subjects with secondary progressive (SP) MS were significantly different from primary progressive (PP) patients (p < 0.001) but similar to relapsing-remitting (RR) patients. Considering subjects with moderate to severe depressive symptoms (BDI II score from 20-63), in relation to disease course, 11.7% (83/710) had RR MS, 40.7% (96/236) SP and 13.6% (6/44) PP. CONCLUSIONS: Using the BDI II, 30% of the current sample had depressive symptoms. BDI II score correlates with disability and disease course, particularly in subjects with SP MS. The BDI II scale can be a useful tool in clinical practice to screen depressive symptoms in people with MS.


Subject(s)
Depression/physiopathology , Disabled Persons , Multiple Sclerosis/physiopathology , Adult , Cross-Sectional Studies , Female , Humans , Italy , Male , Young Adult
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