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Purpose That thyroid hormones exert pleiotropic effects and have a contributory role in triggering seizures in patients with traumatic brain injury (TBI) can be hypothesized. We aimed at investigating thyroid function tests as prognostic factors of the development of seizures and of functional outcome in TBI. Methods This retrospective study enrolled 243 adult patients with a diagnosis of mild-to-severe TBI, consecutively admitted to our rehabilitation unit for a 6-month neurorehabilitation program. Data on occurrence of seizures, brain imaging, injury characteristics, associated neurosurgical procedures, neurologic and functional assessments, and death during hospitalization were collected at baseline, during the workup and on discharge. Thyroid function tests (serum TSH, fT4, and fT3 levels) were performed upon admission to neurorehabilitation. Results Serum fT3 levels were positively associated with an increased risk of late post-traumatic seizures (LPTS) in post-TBI patients independent of age, sex and TBI severity (OR = 1.85, CI 95% 1.22–2.61, p Conclusions Serum fT3 levels assessed in the subacute phase post-TBI are associated with neurological and functional outcome as well as with the risk of seizure occurrence. Further studies are needed to investigate the mechanisms underlying these associations.

We addressed postural instability during stance with eyes closed (EC) on a compliant surface in healthy young people. Spectral analysis of the centre of foot pressure oscillations was used to identify the effects of haptic information (light-touch, EC-LT), or vision (eyes open, EO), or both (EO-LT). Spectral median frequency was strongly reduced by EO and EO-LT, while spectral amplitude was reduced by all “stabilising” sensory conditions. Reduction in spectrum level by EO mainly appeared in the high-frequency range. Reduction by LT was much larger than that induced by the vision in the low-frequency range, less so in the high-frequency range. Touch and vision together produced a fall in spectral amplitude across all windows, more so in anteroposterior (AP) direction. Lowermost frequencies contributed poorly to geometric measures (sway path and area) for all sensory conditions. The same subjects participated in control experiments on a solid base of support. Median frequency and amplitude of the spectrum and geometric measures were largely smaller when standing on solid than on foam base but poorly affected by the sensory conditions. Frequency analysis but not geometric measures allowed to disclose unique tuning of the postural control mode by haptic and visual information. During standing on foam, the vision did not reduce low-frequency oscillations, while touch diminished the entire spectrum, except for the medium-high frequencies, as if sway reduction by touch would rely on rapid balance corrections. The combination of frequency analysis with sensory conditions is a promising approach to explore altered postural mechanisms and prospective interventions in subjects with central or peripheral nervous system disorders.

Introduction Postural instability is a cardinal feature of Parkinson's disease, together with rest tremor, rigidity and bradykinesia. It is a highly disabling symptom that becomes increasingly common with disease progression and represents a major source of reduced quality of life in patients with Parkinson's disease. Rehabilitation aims to enable patients with Parkinson's disease to maintain their maximum level of mobility, activity and independence. To date, a wide range of rehabilitation approaches has been employed to treat postural instability in Parkinson's disease, including robotic training. Our main aim was to conduct a systematic review of current literature about the effects of robot-assisted gait training on postural instability in patients with Parkinson's disease. Evidence acquisition A systematic search using the following MeSH terms "Parkinson disease," "postural balance," "robotics," "rehabilitation" AND string "robotics [mh]" OR "robot-assisted" OR "electromechanical" AND "rehabilitation [mh]" OR "training" AND "postural balance [mh]" was conducted on PubMed, Cochrane Library and Pedro electronic databases. Full text articles in English published up to December 2020 were included. Data about patient characteristics, robotic devices, treatment procedures and outcome measures were considered. Every included article got checked for quality. Level of evidence was defined for all studies. Evidence synthesis Three authors independently extracted and verified data. In total, 18 articles (2 systematic reviews, 9 randomized controlled trials, 4 uncontrolled studies and 3 case series/case reports) were included. Both end-effector and exoskeleton devices were investigated as to robot-assisted gait training modalities. No clear relationship between treatment parameters and clinical conditions was observed. We found a high level of evidence about the effects of robot-assisted gait training on balance and freezing of gait in patients with Parkinson's disease. Conclusions This systematic review provides to the reader a complete overview of current literature and levels of evidence about the effects of robot-assisted gait training on postural instability issues (static and dynamic balance, freezing of gait, falls, confidence in activities of daily living and gait parameters related to balance skills) in patients with Parkinson's disease.

Haemophilia is marked by joint bleeding (haemarthrosis) leading to cartilage damage (arthropathy). Lifelong prophylaxis—initiated after the first bleeding episode—leads to a dramatic decrease in arthropathy in haemophilia patients. However, adherence to continuous intravenous administrations of factor VIII (FVIII) or FIX products is challenging, and patients potentially suffer from breakthrough bleedings while on prophylaxis. Newer FVIII/FIX products with enhanced convenience attributes and/or easier infusion procedures are intended to improve adherence. However, pharmacokinetic data should be harmonised with information from individual attitudes and treatment needs, to tailor intravenous dosing and scheduling in patients who receive extended half-life products. Nor is there sound evidence as to how subcutaneous non-FVIII/FIX replacement approaches (concizumab; emicizumab; fitusiran) or single intravenous injections of adeno-associated viral vectors (when employing gene therapy) will revolutionize adherence in haemophilia. In rheumatoid arthritis, repeated ultrasound examination of a patient's major joints is a valuable tool to educate patients and parents to understand the disease and provide an objective framework for clinicians to acknowledge patient's adherence. Joint ultrasound examination in haemophilia significantly correlates with cartilage damage, effusion, and synovial hypertrophy evaluated by magnetic resonance imaging. Furthermore, in patients with haemophilia undergoing prophylaxis with an extended half-life product for a ≈ 2.8 year period, a significant continued improvement in joint health is detected at the physical examination. This provides the rationale for studies on repeated ultrasound examinations of joint status to attempt to remedy sub-optimal medication adherence and help identify which approach is most suited on which occasion and for which patient.

Abnormalities of body-weight transfer occur during several motor tasks in people with Parkinson’s disease (PwPD). In this paper, a novel robotic paradigm for assessment and training of dynamic balance was developed and applied to twelve healthy subjects (HS) and ten PwPD to verify its feasibility and to assess the capability of PwPD to counteract the postural perturbations through body-weight shifts. At variance with other robotic paradigms, subjects had to react as fast as possible to the perturbation, bringing the platform back to the horizontal and keeping it until the end of the task. Four randomized perturbations, obtained varying the platform equilibrium angle from 0 to ±6° in sagittal (backward, forward) and frontal (right, left) planes, were repeated 3 times. Compared to HS, PwPD showed, in all perturbation directions, increased delay in counteraction phase onset (p

To date, ceftazidime-avibactam (CAZ-AVI) neurotoxicity in patients with normal renal function has not been reported in the literature, and no data about its penetration into the CNS through the blood-brain barrier are available. We report the occurrence of severe encephalopathy in a patient with normal renal function, after the infusion of CAZ-AVI to treat a Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP) sepsis. The radiological and clinical pictures of our patient, and particularly the encephalopathy resolution after drug discontinuation, support the hypothesis of a drug-induced aseptic meningitis (DIAM). The brain MRI-supported meningeal inflammation, along with the increase in blood-CSF-barrier permeability detected on the CSF analysis, could have paved the way for the drug’s neurotoxicity by increasing its CNS entering (the CSF CAZ-AVI level in our patient was higher than the highest value reported in a study on children with meningitis). Neurotoxicity of CAZ-AVI and, by analogy, of other cephalosporins should be recognized as a potential adverse effect even in patients with normal renal function, with an increased risk of severe encephalopathy.

Background. Peripheral fat tissue is known to positively influence bone health. However, evidence exists that the risk of non-vertebral fractures can be increased in postmenopausal women with obesity as compared to healthy controls. The role of sclerostin, the SOST gene protein product, and body composition in this condition is unknown. Methods. We studied 28 severely obese premenopausal (age, 44.7 ± 3.9 years, BMI, 46.0 ± 4.2 kg/m2) and 28 BMI-matched post-menopausal women (age, 55.5 ± 3.8 years, BMI, 46.1 ± 4.8 kg/m2) thorough analysis of bone density (BMD) and body composition by dual X-ray absorptiometry (DXA), bone turnover markers, sclerostin serum concentration, glucose metabolism, and a panel of hormones relating to bone health. Results. Postmenopausal women harbored increased levels of the bone turnover markers CTX and NTX, while sclerostin levels were non-significantly higher as compared to premenopausal women. There were no differences in somatotroph, thyroid and adrenal hormone across menopause. Values of lumbar spine BMD were comparable between groups. By contrast, menopause was associated with lower BMD values at the hip (p &lt, 0.001), femoral neck (p &lt, 0.0001), and total skeleton (p &lt, 0.005). In multivariate regression analysis, sclerostin was the strongest predictor of lumbar spine BMD (p &lt, 0.01), while menopausal status significantly predicted BMD at total hip (p &lt, 0.01), femoral neck (p &lt, 0.001) and total body (p &lt, 0.05). Finally, lean body mass emerged as the strongest predictor of total body BMD (p &lt, 0.01). Conclusions. Our findings suggest a protective effect of obesity on lumbar spine and total body BMD at menopause possibly through mechanisms relating to lean body mass. Given the mild difference in sclerostin levels between pre- and postmenopausal women, its potential actions in obesity require further investigation.

It was highlighted that the original article [1] had an omission in the Abstract. This Correction article shows the omitted sentence: “This article [1] was awarded the SIAMOC Best Methodological Paper 2018”.

Objective: To assess whether the introduction of the new diagnostic criteria and disease modifying therapies (DMTs) is associated with higher cost for treating multiple sclerosis (MS). Methods: This is a regression-based quasi-experimental study employing interrupted time series analysis, including data from 2229 patients (age 42.1 ± 11.2 years; female 63.34%), with incident diagnosis of relapsing remitting MS (RRMS) and followed up from 1997 to 2017, extracted from the database of the MS Clinical Care and Research Centre of the Federico II University Hospital of Naples (Italy). Annual healthcare costs for DMT (e.g., prescription, staff involved in DMT administration) and management (e.g., neurological consultations, other consultations related to DMT safety, MRI, laboratory exams), were calculated and inflated to the most recent value. Results: Annual costs per patient for DMT prescription and management were not affected by the introduction of 2001 and 2005 criteria, but decreased by 0.4% after the introduction of 2011 criteria (PD= -0.4%; 95% C.I. -0.7%/-0.0%; p=0.023). Annual costs per patient increased by 11.2% after the introduction of Natalizumab in 2007 (PD= 11.2%; 95% C.I.= 9.4%/13.0%; p

Purpose Walking is an attention-demanding task that affects and is affected by cognitive performance. Since treadmill walking (TW) assists gait automaticity, we have hypothesized that TW affects cognitive performance to a smaller extent than overground walking (OW). Methods Thirty young adults were recruited. Each subject walked overground over a 20-meter straight hallway at three different speeds (slow, normal and fast). Each task was repeated 3 times under Single Task (OW-ST) and Dual Task (OW-DT) condition, in a randomized sequence. DT was a serial subtraction by 7 starting from a different number (> 100) in each trial. Afterwards, each subject walked on the treadmill at the same three speeds as during OW-ST, while performing the dual task (TW-DT). The correct cognitive response (CCR), calculated from the number of correct responses and mistakes, was compared between rest, OW-DT and TW-DT. Dual-task cost (DTC) was calculated for speed and for CCR. Results Backward counting diminished normal and fast OW-DT speed by about 15 %. Slow OW-DT speed was not significantly reduced. In turn, OW affected the cognitive performance. DTC for speed during OW-DT increased during normal and fast speed. CCR significantly decreased, more at slower OW-DT speed. Conversely, CCR was not worsened by TW-DT. CCR did not decline at slow TW-DT speed and improved significantly from slow and normal to fast speeds. DTC for CCR resulted smaller in TW-DT than OW-DT. Conclusions Decline in the cognitive performance during OW-DT is more prominent at slow speed, in keeping with higher demand of attentional resources for this unusual locomotor behaviour. Conversely, motorized TW improves the cognitive performance likely because it reduces the attentional cost of walking. Gait training by TW might improve automaticity in patients with movement disorders.

Unilateral axial muscle vibration, eliciting a proprioceptive volley, is known to incite steering behavior. Whole-body rotation while stepping in place also occurs as an after-effect of stepping on a circular treadmill (podokinetic after-rotation, PKAR). Here, we tested the hypothesis that PKAR is modulated by axial muscle vibration. If both phenomena operate through a common pathway, enhancement or cancellation of body rotation would occur depending on the stimulated side when vibration is administered concurrently with PKAR. Seventeen subjects participated in the study. In one session, subjects stepped in place eyes open on the center of a platform that rotated counterclockwise 60°/s for 10 min. When the platform stopped, subjects continued stepping in place blindfolded. In other session, a vibratory stimulus (100 Hz, 2 min) was administered to right or left paravertebral muscles at lumbar level at two intervals during the PKAR. We computed angular body velocity and foot step angles from markers fixed to shoulders and feet. During PKAR, all subjects rotated clockwise. Decreased angular velocity was induced by right vibration. Conversely, when vibration was administered to the left, clockwise rotation velocity increased. The combined effect on body rotation depended on the time at which vibration was administered during PKAR. Under all conditions, foot step angle was coherent with shoulder angular velocity. PKAR results from continuous asymmetric input from the muscles producing leg rotation, while axial muscle vibration elicits a proprioceptive asymmetric input. Both conditioning procedures appear to produce their effects through a common mechanism. We suggest that both stimulations would affect our straight ahead by combining their effects in an algebraic mode.

Several studies associate foetal human exposure to bisphenol A (BPA) to metabolic/endocrine diseases, mainly diabesity. They describe the role of BPA in the disruption of pancreatic beta cell, adipocyte and hepatocyte functions. Indeed, the complexity of the diabesity phenotype is due to the involvement of different endoderm-derived organs, all targets of BPA. Here, we analyse this point delineating a picture of different mechanisms of BPA toxicity in endoderm-derived organs leading to diabesity. Moving from epidemiological data, we summarize the in vivo experimental data of the BPA effects on endoderm-derived organs (thyroid, pancreas, liver, gut, prostate and lung) after prenatal exposure. Mainly, we gather molecular data evidencing harmful effects at low-dose exposure, pointing to the risk to human health. Although the fragmentation of molecular data does not allow a clear conclusion to be drawn, the present work indicates that the developmental exposure to BPA represents a risk for endoderm-derived organs development as it deregulates the gene expression from the earliest developmental stages. A more systematic analysis of BPA impact on the transcriptomes of endoderm-derived organs is still missing. Here, we suggest in vitro toxicogenomics approaches as a tool for the identification of common mechanisms of BPA toxicity leading to the diabesity in organs having the same developmental origin.

Among traumatic brain injuries, acute subdural hematoma (aSDH) is considered one of the most devastating still retaining poor surgical outcomes in a considerable percentage of affected patients. However, according to results drawn from published samples of aSDH patients, overall mortality and functional recovery have been progressively ameliorating during the last decades.We present a retrospective analysis of 316 consecutive cases of post-traumatic aSDH operated on between 2003 and 2011 at our institution.Mortality was 67% (n = 212); a useful recovery was achieved in 16.4% cases (n = 52). Age65 years, a preoperative Glasgow coma scale (GCS) ≤ 8, specific pre-existing medical comorbidities (hypertension, heart diseases) were found to be strong indicators of unfavorable outcomes and death during hospitalization.Our results, compared with those of the inherent literature, led the authors to question both the "aggressiveness" of neurosurgical care indications in certain subpopulations of patients being known to fare worse or even die regardless of the treatment administered and the relevance of the results concerning mortality and functional recovery reported by third authors.

Various diseases are associated with the impaired control of the medio-lateral (ML) position of the centre of feet pressure (CoP), and several manoeuvres have been proposed for enhancing the CoP symmetry. Here, we assessed in healthy standing subjects the feasibility and outcome of a novel protocol entailing a reaction to a continuous asymmetric ML displacement (10 cm) of the support base. The periodic perturbation consisted of a fast half-cycle (0.5 Hz) followed by a slow half-cycle (0.18 Hz). One hundred successive horizontal translation cycles were delivered in sequence. Eyes were open or closed. CoP was recorded before, after, and during the stimulation by a dynamometric platform fixed onto the translating platform. We found that the post-stimulation CoP was displaced towards the direction of the fast half-cycles. The displacement lasted several tens of seconds. Vision did not affect the amplitude or duration of the post-stimulation effect. The magnitude of post-stimulation CoP displacement was related to the perturbation-induced ML motion of CoP recorded during the stimulation. Over the successive perturbation cycles, the time-course of this motion revealed an adaptation phenomenon. Vision moderately reduced the adaptation rate. The findings support the feasibility of the administration of a simple asymmetric balance perturbation protocol in clinical settings to help patients recover the symmetry of the CoP. This protocol needs to be further validated in older populations and in patients.

AimThe aim of the present study was to assess the estimated "per patient" total cost for a single Oncologic Italian Cancer Center participating in a multicenter clinical trial with new anticancer biological agents using the activity-based costing (ABC) methodology.MethodologyNine randomized phase 3 clinical trials employing biological agents at the National Cancer Institute of Napoli, Italy, were analyzed to indentify "per patient" costs of each trial, according to the ABC methodology. The average consumption of resources for a patient completing the entire planned treatment was estimated for each trial. Through interviews of the personnel (doctors, nurses and technicians) and by analyses of the clinical trials protocols, the main activities of the 9 clinical trials were identified and, for each trial, the complete health care pathway of the patients and the treatment programmes were minutely reconstructed. Drug costs were not included because provided by Sponsors.Principal findingsThe average costs of the pre-study, treatment, monitoring, follow-up, audit, and administrative activities accounted for 2.357, 4.783, 700, 372, 1.263, and 9 Euro, respectively. The average total cost estimated for all "per patient" activities, including overhead costs, was 11.379 Euro. Staff costs accounted for € 5.988, while costs of diagnostic test accounted for 3.494 Euro. Clinical trials with immunotherapeutic drugs accounted for higher costs (+601 Euro as oncological staff costs, +1.318 Euro as intermediate services cost and +384 Euro as overheads).ConclusionsThe average total cost estimated for all "per patient" activities of a clinical trial with new anticancer biological agents was 11.379 Euro using the ABC methodology.

Background Several patients with Parkinson´s disease (PD) can walk normally along straight trajectories, and impairment in their stride length and cadence may not be easily discernible. Do obvious abnormalities occur in these high-functioning patients when more challenging trajectories are travelled, such as circular paths, which normally implicate a graded modulation in the duration of the interlimb gait cycle phases? Methods We compared a cohort of well-treated mildly to moderately affected PD patients to a group of age-matched healthy subjects (HS), by deliberately including HS spontaneously walking at the same speed of the patients with PD. All participants performed, in random order: linear and circular walking (clockwise and counter-clockwise) at self-selected speed. By means of pressure-sensitive insoles, we recorded walking speed, cadence, duration of single support, double support, swing phase, and stride time. Stride length-cadence relationships were built for linear and curved walking. Stride-to-stride variability of temporal gait parameters was also estimated. Results Walking speed, cadence or stride length were not different between PD and HS during linear walking. Speed, cadence and stride length diminished during curved walking in both groups, stride length more in PD than HS. In PD compared to HS, the stride length-cadence relationship was altered during curved walking. Duration of the double-support phase was also increased during curved walking, as was variability of the single support, swing phase and double support phase. Conclusion The spatio-temporal gait pattern and variability are significantly modified in well-treated, high-functioning patients with PD walking along circular trajectories, even when they exhibit no changes in speed in straight-line walking. The increased variability of the gait phases during curved walking is an identifying characteristic of PD. We discuss our findings in term of interplay between control of balance and of locomotor progression: the former is challenged by curved trajectories even in high-functioning patients, while the latter may not be critically affected.

We hypothesised that rehabilitation specifically addressing balance in Parkinson’s disease patients might improve not only balance but locomotion as well. Two balance-training protocols (standing on a moving platform and traditional balance exercises) were assessed by assigning patients to two groups (Platform,n=15, and Exercises,n=17). The platform moved periodically in the anteroposterior, laterolateral, and oblique direction, with and without vision in different trials. Balance exercises were based on the Otago Exercise Program. Both platform and exercise sessions were administered from easy to difficult. Outcome measures were (a) balancing behaviour, assessed by both Index of Stability (IS) on platform and Mini-BESTest, and (b) gait, assessed by both baropodometry and Timed Up and Go (TUG) test. Falls Efficacy Scale-International (FES-I) and Parkinson’s Disease Questionnaire (PDQ-8) were administered. Both groups exhibited better balance control, as assessed both by IS and by Mini-BESTest. Gait speed at baropodometry also improved in both groups, while TUG was less sensitive to improvement. Scores of FES-I and PDQ-8 showed a marginal improvement. A four-week treatment featuring no gait training but focused on challenging balance tasks produces considerable gait enhancement in mildly to moderately affected patients. Walking problems in PD depend on postural instability and are successfully relieved by appropriate balance rehabilitation. This trial is registered with ClinicalTrials.govNCT03314597.

Background: Normal pelvic visceral function depends on the complex interactions of intact somatic and autonomic nervous systems. Living with polio increases the risk of having bladder dysfunction. Urinary problems in polio infection may occur because the pelvic floor and bladder detrusor muscles have been paralyzed by the poliovirus. Neurophysiological tests should include electromyography (EMG), nerve conduction studies and the evaluation of the sacral reflexes in order to investigate the integrity of the somatic innervation of the pelvic floor muscles and urinary and anal sphincters. Case Report: This is a case of a 53-year-old South- American man who had a history of poliomyelitis which affected his lower right limb when he was 2-years old. The patient was unable to empty his bladder completely. The aim of this paper is to describe the correlation between pelvic floor dysfunction, bladder symptoms and neurophysiological tests because this concept has not been investigated adequately in literature. Conclusion: Neurophysiological diagnostic procedures adopted in our study can discern the degree of central and peripheral nervous system damage and confirmed that pelvic floor and detrusor muscles have been paralyzed by the poliovirus, in order to perform a personalized rehabilitation treatment.

Objectives: To assess the efficacy of a leg exercise performed in supine position to prevent orthostatic hypotension (OH) in older adults. Design: Case�control study. Setting: Division of Physical Medicine and Rehabilitation, Salvatore Maugeri Foundation, Scientific Institute of Veruno, Veruno, Italy. Participants: Individuals aged 65 and older admitted with degenerative joint disease screened (n = 90) and found positive for OH (n = 42). Measurements: Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were recorded using an automatic oscillometric device in the supine position after 10 minutes of bed rest; immediately upon standing up; and after 1, 3 and 5 minutes standing. In 42 participants, a fall in SBP of 20 mmHg or more within 3 minutes of standing was found. Participants with OH were alternately assigned to the control or exercise group. The following day, both groups were reassessed as above. In the exercise group, before standing up, participants were required to perform 10 full extensions of the lower limbs, starting from 60° flexion of hip and 90° flexion of knee and ankle joints, against the resistance of an elastic band. Results : In both participant groups, SBP, DBP, and HR were similar in the supine position. When standing, the same decrease in SBP and DBP and increase in HR occurred over a similar time-course in both participant groups. The next day, the reduction in SBP was significantly smaller at each time interval after standing up in the exercise than in the control group, but no difference between the exercise and control groups was observed in DBP or HR. Conclusion: Supine leg exercise is effective in reducing an initial fall in SBP when passing from a supine to an upright position in older adults. The duration of the effect requires further investigation.

Training subjects to step-in-place eyes-open on a rotating platform while maintaining a fixed body orientation in space (podokinetic stimulation, PKS) produces a post-effect consisting in inadvertent turning around while stepping-in-place eyes-closed (podokinetic after-rotation, PKAR). Since the rationale for rehabilitation of curved walking in Parkinson's disease is not fully known, we tested the hypothesis that repeated PKS favours the production of curved walking in these patients, who are uneasy with turning, even when straight walking is little affected. Fifteen patients participated in ten training sessions distributed in three weeks. Both counter-clockwise and clockwise PKS were randomly administered in each session. PKS velocity and duration were gradually increased over sessions. The velocity and duration of the following PKARs were assessed. All patients showed PKAR, which increased progressively in peak velocity and duration. In addition, before and at the end of the treatment, all patients walked over-ground along linear and circular trajectories. Post-training, the velocity of walking bouts increased, more so for the circular than the linear trajectory. Cadence was not affected. This study has shown that Parkinsonian patients learn to produce turning while stepping when faced with appropriate training, and that this capacity translates into improved over-ground curved walking.

Background Recently, a new tool for assessing dynamic balance impairments has been presented: the 14-item Mini-BESTest. Objective The aim of this study was to compare the psychometric performance of the Mini-BESTest and the Berg Balance Scale (BBS). Design A prospective, single-group, observational design was used in the study. Methods Ninety-three participants (mean age=66.2 years, SD=13.2; 53 women, 40 men) with balance deficits were recruited. Interrater (3 raters) and test-retest (1–3 days) reliability were calculated using intraclass correlation coefficients (ICCs). Responsiveness and minimal important change were assessed (after 10 sessions of physical therapy) using both distribution-based and anchor-based methods (external criterion: the 15-point Global Rating of Change [GRC] scale). Results At baseline, neither floor effects nor ceiling effects were found in either the Mini-BESTest or the BBS. After treatment, the maximum score was found in 12 participants (12.9%) with BBS and in 2 participants (2.1%) with Mini-BESTest. Test-retest reliability for total scores was significantly higher for the Mini-BESTest (ICC=.96) than for the BBS (ICC=.92), whereas interrater reliability was similar (ICC=.98 versus .97, respectively). The standard error of measurement (SEM) was 1.26 and the minimum detectable change at the 95% confidence level (MDC95) was 3.5 points for Mini-BESTest, whereas the SEM was 2.18 and the MDC95 was 6.2 points for the BBS. In receiver operating characteristic curves, the area under the curve was 0.92 for the Mini-BESTest and 0.91 for the BBS. The best minimal important change (MIC) was 4 points for the Mini-BESTest and 7 points for the BBS. After treatment, 38 participants evaluated with the Mini-BESTest and only 23 participants evaluated with the BBS (out of the 40 participants who had a GRC score of ≥3.5) showed a score change equal to or greater than the MIC values. Limitations The consecutive sampling method drawn from a single rehabilitation facility and the intrinsic weakness of the GRC for calculating MIC values were limitations of the study. Conclusions The 2 scales behave similarly, but the Mini-BESTest appears to have a lower ceiling effect, slightly higher reliability levels, and greater accuracy in classifying individual patients who show significant improvement in balance function.

Summary Study objective To assess whether gait abnormalities in COPD depend on mere impairment of respiratory function. Methods In 40 patients with COPD at different GOLD stages and 28 controls, we evaluated: forced expiratory volume in 1 s (FEV1); partial pressure of oxygen; Mini-Mental State Examination (MMSE); dynamic balance through the Mini-BESTest (MBT); Timed Up and Go (TUG) test without and with dual task counting aloud back by three; 6-min walk test (6MWT); body sway during quiet stance (stabilometry); spatial-temporal variables of gait by a 4-m long sensorized walkway (baropodometry). Lower-limb muscle strength, tendon reflexes, and sensation were also clinically evaluated. Results Muscle strength of proximal but not distal muscles was slightly reduced in patients, whereas reflexes and sensation were unaffected. FEV1, partial pressure of oxygen, MMSE, MBT, stabilometry, as well as baropodometry, were abnormal and unrelated to muscle weakness. The time taken to perform the TUG test was increased, and to a larger extent with than without dual task. At baropodometry, variability of step length was increased; abnormalities of gait variables were associated with larger body sway but not with FEV1 or hypoxemia. Gait speed at 6MWT was correlated with MBT score and with FEV1 as well as hypoxemia. Conclusions 6MWT findings give a measure of gait disability linked to endurance-related respiratory failure. Gait at baropodometry is associated with impairment of balance, cognitive status and abnormal dual task performance. We suggest that central nervous lesions, presumably of vascular origin, are detrimental to balance and gait in COPD.

Background Single-level cervical radiculopathy may be treated conservatively with cervical tractions. Posterior cervical transfacet fusion with a facetal spacer is a viable option. The aim of the present study is to compare posterior cervical transfacet fusion with conservative physical treatment in single-level cervical radiculopathy. Methods A total of 80 patients were randomized in 2 groups, a surgical group in which patients were given posterior cervical transfacet fusion and a traction group in which patients were treated conservatively with mechanical cervical tractions. Visual analog scale for arm and neck, Neck Disability Index, and Short Form-36 (SF-36) questionnaires were administered preoperatively and after treatment up to 12 months. Results After treatment, visual analog scale arm scores were greater in traction group (4.7 vs. 1.5 the day after treatment) and at follow-up controls (traction group vs. surgical group: 5.3 vs. 0.6 at 1 month, 3.6 vs. 0.3 at 6 months, 1.8 vs. 0.2 at 12 months). Neck Disability Index scores were lower in the surgical group (surgical group vs. traction group: 4.4 vs. 20.3 at 1 month, 1.3 vs. 10.5 at 6 months). SF-36 scores were greater in the surgical group (surgical group vs. traction group: 96 vs. 70 at 1 month, 96.5 vs. 82.6 at 6 months). Neck disability index and SF-36 scores were superimposable between the groups at 12-month follow-up. No adjacent-segment arthrosis or late complications were reported at 1-year follow-up in the surgical group. Conclusions posterior cervical transfacet fusion is a safe and effective procedure to treat single-level cervical radiculopathy.

It has been largely suggested in neuroscience literature that to generate a vast variety of movements, the Central Nervous System (CNS) recruits a reduced set of coordinated patterns of muscle activities, defined as muscle synergies. Recent neurophysiological studies have recommended the analysis of muscle synergies to finely assess the patient's impairment, to design personalized interventions based on the specific nature of the impairment, and to evaluate the treatment outcomes. In this scope, the aim of this study was to design a personalized multi-channel functional electrical stimulation (FES) controller for gait training, integrating three novel aspects: (1) the FES strategy was based on healthy muscle synergies in order to mimic the neural solutions adopted by the CNS to generate locomotion; (2) the FES strategy was personalized according to an initial locomotion assessment of the patient and was designed to specifically activate the impaired biomechanical functions; (3) the FES strategy was mapped accurately on the altered gait kinematics providing a maximal synchronization between patient's volitional gait and stimulation patterns. The novel intervention was tested on two chronic stroke patients. They underwent a 4-week intervention consisting of 30-min sessions of FES-supported treadmill walking three times per week. The two patients were characterized by a mild gait disability (walking speed > 0.8 m/s) at baseline. However, before treatment both patients presented only three independent muscle synergies during locomotion, resembling two different gait abnormalities. After treatment, the number of extracted synergies became four and they increased their resemblance with the physiological muscle synergies, which indicated a general improvement in muscle coordination. The originally merged synergies seemed to regain their distinct role in locomotion control. The treatment benefits were more evident for one patient, who achieved a clinically important change in dynamic balance (Mini-Best Test increased from 17 to 22) coupled with a very positive perceived treatment effect (GRC = 4). The treatment had started the neuro-motor relearning process also on the second subject, but twelve sessions were not enough to achieve clinically relevant improvements. This attempt to apply the novel theories of neuroscience research in stroke rehabilitation has provided promising results, and deserves to be further investigated in a larger clinical study.

Epidemiological and experimental evidence associates the exposure to Bisphenol A with the increase of cancer risk in several organs, including prostate. BPA targets different pathways involved in carcinogenicity including the Nuclear Receptors (i.e. estrogen and androgen receptors), stress regulated proteins and, finally, epigenetic changes. Here, we analyse BPA-dependent carcinogenesis in endoderm-derived glands, thyroid, liver, pancreas and prostate focusing on cell signalling, DNA damage repair pathways and epigenetic modifications. Mainly, we gather molecular data evidencing harmful effects at doses relevant for human risk (low-doses). Since few molecular data are available, above all for the pancreas, we analysed transcriptomic data generated in our laboratory to suggest possible mechanisms of BPA carcinogenicity in endoderm-derived glands, discussing the role of nuclear receptors and stress/NF-kB pathways. We evidence that an in vitro toxicogenomic approach might suggest mechanisms of toxicity applicable to cells having the same developmental origin. Although we cannot draw firm conclusions, published data summarized in this review suggest that exposure to BPA, primarily during the developmental stages, represents a risk for carcinogenesis of endoderm-derived glands.

Motor adaptation due to task practice implies a gradual shift from deliberate control of behavior to automatic processing, which is less resource- and effort-demanding. This is true both for deliberate aiming movements and for more stereotyped movements such as locomotion and equilibrium maintenance. Balance control under persisting critical conditions would require large conscious and motor effort in the absence of gradual modification of the behavior. We defined time-course of kinematic and muscle features of the process of adaptation to repeated, predictable perturbations of balance eliciting both reflex and anticipatory responses. Fifty-nine sinusoidal (10 cm, 0.6 Hz) platform displacement cycles were administered to 10 subjects eyes-closed (EC) and eyes-open (EO). Head and Center of Mass (CoM) position, ankle angle and Tibialis Anterior (TA) and Soleus (Sol) EMG were assessed. EMG bursts were classified as reflex or anticipatory based on the relationship between burst amplitude and ankle angular velocity. Muscle activity decreased over time, to a much larger extent for TA than Sol. The attenuation was larger for the reflex than the anticipatory responses. Regardless of muscle activity attenuation, latency of muscle bursts and peak-to-peak CoM displacement did not change across perturbation cycles. Vision more than doubled speed and the amount of EMG adaptation particularly for TA activity, rapidly enhanced body segment coordination, and crucially reduced head displacement. The findings give new insight on the mode of amplitude- and time-modulation of motor output during adaptation in a balancing task, advocate a protocol for assessing flexibility of balance strategies, and provide a reference for addressing balance problems in patients with movement disorders.

Early Parkinson's disease (PD), in which the motor disorder is mostly unilateral, allows to investigate the presence of side-related pathophysiological changes in the responses to balance perturbations prior to any confounding effect of therapy. These patients offer the possibility of answering the question whether the initial abnormalities affect spinal circuits or supra-spinal sensori-motor loops. Toe-down rotation of a supporting platform evokes in standing subjects a double-burst medium-latency response (MLR) in the stretched tibialis anterior (TA) muscle. The former burst (MLR1) is fed by group II spindle fibres through a spinal circuit, the latter (MLR2) travels through supraspinal pathways. This perturbation was used to separately test both reflex pathways in both the unaffected and affected side. Ten patients with unilateral PD (7 of which de-novo ) and 10 normal subjects (NS) were recruited. 1. Body sway and centre of feet pressure (CFP) were recorded during quiet standing; 2. Rotations of the supporting platform were administered with both legs on the platform during free stance (Control) and 3. While holding onto a stable rail (Holding); 4. Separate perturbations to either leg (Leg-on or Leg-off) were also delivered to avoid the effect of concurrent ipsi- and contralateral inputs on MLR. The EMG of TA and Sol muscles were recorded bilaterally. 1. Position and sway of CFP were similar in NS and PD. 2. Under Control condition, there were no differences in area of TA MLR1 and MLR2 of both limbs between NS and PD. 3. During Holding, both bursts were reduced in amplitude in both NS and PD, but less so for the MLR1 on the PD affected side. 4. During single-leg perturbation, both bursts were reduced in amplitude in both NS and PD, both ipsi- and contralateral to the perturbation; however, in PD, MLR2 was much less reduced in the unperturbed affected side Leg-off. The differences in the responses to stretch between NS and early PD are not accounted for by changes in postural attitude, or by different amplitudes of the Control responses. The asymmetrical reduction of the MLR1 by Holding in PD indicates mostly unilateral impairment of the descending pathways modulatory to spinal group II circuits. Single-leg perturbation unveils a larger excitability of the supraspinal loop mediating the MLR2 on the affected side. These changes are early markers of basal ganglia malfunctions, and are related to both their descending effect on the spinal cord and their ascending influence onto the cortex.

Objective: To improve, with the aid of psychometric analysis, the Balance Evaluation Systems Test (BESTest), a tool designed to analyse several postural control systems that may contribute to poor functional balance in adults. Methods: Performance of the BESTest was examined in a convenience sample of 115 consecutive adult patients with diverse neurological diagnoses and disease severity, referred to rehabilitation for balance disorders. Factor (both explorative and confirmatory) and Rasch analysis were used to process the data in order to produce a new, reduced and coherent balance measurement tool. Results: Factor analysis selected 24 out of the 36 original BESTest items likely to represent the unidimensional construct of “dynamic balance”. Rasch analysis was then used to: (i) improve the rating categories, and (ii) delete 10 items (misfitting or showing local dependency). The model consisting of the remaining 14 tasks was verified with confirmatory factor analysis to meet the stringent requirements of modern measurement. Conclusion: The new 14-item scale (dubbed mini-BESTest) focuses on dynamic balance, can be conducted in 10–15 min, and contains items belonging evenly to 4 of the 6 sections from the original BESTest. Further studies are needed to confirm the usefulness of the mini-BESTest in clinical settings.

In patients with spastic hemiparesis, centre of foot pressure (CoP) is shifted toward the unaffected limb during quiet stance. We hypothesised that abnormal gait features would correlate with the degree of asymmetry during stance. In 15 patients and 17 normals we recorded CoP and body sway by a force platform and measured spatial-temporal variables of gait with pedobarography. In patients CoP was shifted toward the unaffected limb and sway was larger than in normals. CoP position was associated with the decrease in strength of the affected lower-limb muscles. Spatio-temporal variables of gait were also affected by the disease. Cadence and velocity were decreased, duration of single support on the unaffected limb and of double support were increased with respect to normals. The degree of impairment of gait variables correlated with CoP. We found a negative relationship between velocity or cadence and CoP, and a positive relationship between duration of single support and CoP in the unaffected but not in the affected limb. Duration of double support correlated positively with CoP. CoP asymmetry during both standing and walking suggests that postural and gait problems share some common neural origin in hemiparetic patients. This asymmetry affects gait performance by increasing the time and effort needed to shift body weight toward the affected limb. The degree of postural asymmetry measured by stabilometry is associated with the level of impairment of gait variables.

Patients suffering from Parkinson's disease (PD) have difficulties with control of stance, postural changes, and walking, seemingly depending on problems in central integration of proprioceptive information. We tested the hypothesis that alternate vibration of postural muscles can induce cyclic medio-lateral or antero-posterior sway in PD, mimicking that accompanying body progression during walking, thereby favoring the production of locomotor tasks. In 12 standing PD patients and 11 healthy subjects, we applied trains of vibratory stimuli, bilaterally in an alternating paradigm to soleus, tibialis anterior, or paravertebral muscles. The trains of stimuli were delivered at frequencies selected to be above, near, and below the normal walking rhythm. The displacement of the center of foot pressure (CoP) was recorded. In PD, sway area during unperturbed stance was just larger than in healthy subjects; shifts in CoP in response to vibration were preserved, regardless of the vibrated muscle pair; CoP oscillations along medio-lateral, but not antero-posterior direction, were coupled to the vibration trains; time to initiate and terminate the postural responses was normal. PD patients correctly integrate and exploit the vibration-induced proprioceptive inflow to produce body oscillations comparable to those occurring during walking. Vibratory stimulation can be safely and easily employed to provoke rhythmic postural changes in PD.

Objective Balance control under static and dynamic conditions was assessed in patients with Sensory Neuron Disease (SND) in order to shed further light on the pathophysiology of ataxia. Methods Fourteen patients with diabetic polyneuropathy and 11 with SND underwent clinical and neurophysiological evaluation, stabilometric recording of body sway during quiet stance with and without vision, stereometric analysis of body segment displacement while riding a platform translating in anterior–posterior direction with and without vision (dynamic condition), and EMG recording of leg muscle responses to abrupt stance perturbation produced by rotation of a supporting platform. The findings were compared to those of age matched normal subjects. Results Clinical and neurophysiological evaluation revealed a more severe motor impairment in patients with diabetes than SND, while sensory impairment was superimposable. Some patients with SND had vestibular dysfunction of diverse severity. Body sway during stance was larger in patients with SND than diabetes with and without vision. In the stance perturbation condition, the latency of the long-loop EMG response to platform rotation was disproportionately increased with respect to the spinal response in the SND but not in diabetic patients. Under dynamic condition, patients with SND oscillated more than diabetic patients and several of them easily lost balance with eyes closed. Conclusions Patients with SND show severe unsteadiness under both static and dynamic conditions, particularly with eyes closed. The patchy sensory loss of SND, disrupting sensation from territories other than the lower limbs and possibly including the vestibular nerve, could be responsible for this instability. Ataxia is correlated to the abnormal latency of the muscle responses to stance perturbation. Since increased response latencies cannot be attributed to a vestibular deficit, the deterioration of equilibrium control would be ascribed mainly to the degeneration of the central branch of the afferent fibres. Significance Measures of body balance under quiet stance and dynamic conditions can provide relevant diagnostic information as to the pathophysiology and severity of ataxia and viability of the central branch of the sensory fibres, and help in separating patients with peripheral neuropathy from patients with loss of sensory neurones.

Purpose Cycle ergometer training improves gait in the elderly, but its effect in patients with Parkinson's disease (PD) is not completely known. Methods Twenty-nine PD inpatients were randomized to treadmill (n = 13, PD-T) or cycle ergometer (n = 16, PD-C) training for 3 weeks, 1 hour/day. Outcome measures were distance travelled during the 6-min walking test (6MWT), spatio-temporal variables of gait assessed by baropodometry, the Timed Up and Go (TUG) duration, the balance score through the Mini-BESTest, and the score of the Unified Parkinson's Disease Rating Scale (UPDRS). Results Sex, age, body mass index, disease duration, Hoehn-Yahr staging, comorbidity and medication did not differ between groups. At end of training, ANCOVA showed significant improvement, of similar degree, in both groups for 6MWT, speed, step length and cadence of gait, TUG, Mini-BESTest and UPDRS. Conclusions This pilot study shows that cycle ergometer training improves walking parameters and reduces clinical signs of PD, as much as treadmill training does. Gait velocity is accompanied by step lengthening, making the gait pattern close to that of healthy subjects. Cycle ergometer is a valid alternative to treadmill for improving gait in short term in patients with PD.

The aim of this investigation was to assess the potentially different effects of impaired proprioceptive input in balance control under static and dynamic conditions in neuropathic patients. We recruited 20 normal subjects and 27 patients affected by neuropathies known to affect to a different extent large and medium size afferent fibres. The patients comprised 5 with Charcot-Marie-Tooth disease type 1A (CMT1A), 8 with CMT type 2 (CMT2) and 14 with Diabetes polyneuropathy (Diabetics). Measurement of balance during quiet stance on a stabilometric platform showed that sway area (SA) was larger in the CMT2 and Diabetics than normal subjects or in CMT1A, under both eyes open and closed conditions. The estimated conduction velocity (CV) of the group II afferent fibres was lower in CMT2 and Diabetics than in normal subjects and CMT1A. Across all patients, SA increased as a function of the slowing of group II CV. During a dynamic balance task the head A-P displacement was only slightly increased in the patient groups with respect to normals, despite the increased delay at which the head followed displacement of the feet. The unpredictably good performance of all patient groups under dynamic condition, which was at variance with their imbalance during quiet stance, may indicate that these patients learnt to exploit anticipatory postural strategies.

Solitary brain metastases from uterine carcinoma are uncommon. Intracranial metastases from uterus usually occur in widely disseminated disease. We report three cases of solitary brain metastasis from uterine cancer. In one of these patients metastasis was detected prior to diagnosis of primitive cancer. In a review of the literature only seven cases of solitary brain metastasis preceding the diagnosis of uterine cancer have been documented.

We hypothesised that, since anomalous neck proprioceptive input can produce perturbing effects on posture, neck muscle fatigue could alter body balance control through a mechanism connected to fatigue-induced afferent inflow. Eighteen normal subjects underwent fatiguing contractions of head extensor muscles. Sway during quiet stance was recorded by a dynamometric platform, both prior to and after fatigue and recovery, with eyes open and eyes closed. After each trial, subjects were asked to rate their postural control. Fatigue was induced by having subjects stand upright and exert a force corresponding to about 35% of maximal voluntary effort against a device exerting a head-flexor torque. The first fatiguing period lasted 5 min (F1). After a 5-min recovery period (R1), a second period of fatiguing contraction (F2) and a second period of recovery (R2) followed. Surface EMG activity from dorsal neck muscles was recorded during the contractions and quiet stance trials. EMG median frequency progressively decreased and EMG amplitude progressively increased during fatiguing contractions, demonstrating that muscle fatigue occurred. After F1, subjects swayed to a larger extent compared with control conditions, recovering after R1. Similar findings were obtained after F2 and after R2. Although such behaviour was detectable under both visual conditions, the effects of fatigue reached significance only without vision. Subjective scores of postural control diminished when sway increased, but diminished more, for equal body sway, after fatigue and recovery. Contractions of the same duration, but not inducing EMG signs of fatigue, had much less influence on body sway or subjective scoring. We argue that neck muscle fatigue affects mechanisms of postural control by producing abnormal sensory input to the CNS and a lasting sense of instability. Vision is able to overcome the disturbing effects connected with neck muscle fatigue.

Corna S, Nardone A, Prestinari A, Galante M, Grasso M, Schieppati M. Comparison of Cawthorne-Cooksey exercises and sinusoidal support surface translations to improve balance in patients with unilateral vestibular deficit. Arch Phys Med Rehabil 2003;84:1173–84. Objective: To compare the effectiveness of vestibular rehabilitation by using Cawthorne-Cooksey exercises with that of instrumental rehabilitation. Design: The main study (n=32) used a pre-post rehabilitation (A-B) design; the ancillary studies used a subset of 11 patients 1 month before rehabilitation versus pre-post rehabilitation (A-A-B design) and 9 patients pre-post rehabilitation versus 1 month after (A-B-B design). Setting: Division of physical therapy and rehabilitation at a scientific institute in Italy. Participants: Patients (Cawthorne-Cooksey, n=17; instrumental rehabilitation, n=15) with a complete or incomplete unilateral vestibular lesion due to ischemic, inflammatory, cranial nerve VIII sectioning, or unknown cause. Interventions: Cawthorne-Cooksey exercises or instrumental rehabilitation training consisting of standing with eyes open (EO) or closed (EC) on a platform moving, relative to the subjects, in the anteroposterior (AP) or mediolateral direction, at a sinusoidal translation frequency of 0.2 or 0.6Hz; training sessions for both interventions were twice daily, 30 minutes per session, for 5 days. Main Outcome Measures: Body sway and subjective score of sway during quiet stance with EO or EC, with feet 10cm apart (FA) or together (FT); the standard deviation of the AP displacement of the malleolus, hip, and head during AP platform translations; the Dizziness Handicap Inventory (DHI); and performance-oriented evaluation of balance and gait (according to Tinetti). Results: Both interventions improved patients' balance. Under each postural and visual condition, both groups showed reduction in body sway, and the post rehabilitation sway values approached those observed in normal subjects; improvement was significantly better for instrumental rehabilitation under FA EO, FA EC, and FT EC conditions. All patients reported a subjective feeling of increased steadiness. Sway recorded 1 month before treatment did not differ from that at the start of treatment. The follow-up evaluation showed persistence of effect. Parallel to the improved stability, a decrease in the SD of the displacement of hip and head in balancing on the movable platform was present in both groups; improvement was better in the instrumental rehabilitation group than the Cawthorne-Cooksey group under the EC condition. Balance and gait assessment improved to the same extent in both groups. Scores on the physical, functional, and emotional questions of the DHI improved significantly in both groups after treatment, but to a larger extent in the instrumental rehabilitation patients. Conclusions: Both Cawthorne-Cooksey and instrumental rehabilitation are effective for treating balance disorders of vestibular origin. Improvement affects both control of body balance and performance of activities of daily living. The larger decrease in body sway and greater improvement of DHI after instrumental rehabilitation suggests that it is more effective than Cawthorne-Cooksey exercises in improving balance control.

This study presents an innovative multi-channel neuroprosthesis that induces a biomimetic activation of the main lower-limb muscles during treadmill gait training to be used in the rehabilitation of stroke patients. The electrostimulation strategy replicates the physiological muscle synergies used by healthy subjects to walk on a treadmill at their self-selected speed. This strategy is mapped to the current gait sub-phases, which are identified in real time by a custom algorithm. This algorithm divides the gait cycle into six sub-phases, based on two inertial sensors placed laterally on the shanks. Therefore, the pre-defined stimulation profiles are expanded or stretched based on the actual gait pattern of each single subject. A preliminary experimental protocol, involving 10 healthy volunteers, was carried out to extract the muscle synergies and validate the gait-detection algorithm, which were afterwards used in the development of the neuroprosthesis. The feasibility of the neuroprosthesis was tested on one healthy subject who simulated different gait patterns, and a chronic stroke patient. The results showed the correct functioning of the system. A pilot study of the neurorehabilitation treatment for stroke patients is currently being carried out.

Objectives: Adherence to treatment is of utmost importance in multiple sclerosis (MS) to achieve full benefits from disease-modifying treatments. Thus, we investigated predictors of adherence to interferon beta-1a. Methods: 114 relapsing-remitting MS subjects were recruited and followed-up during 1.536 +/- 0.961 years. RebiSmart (R) (Ares Trading SA, Coinsins, Switzerland), an electronic auto-injector, allows real-time recording of adherence which was retrospectively evaluated, and subjects were categorized accordingly: fully adherent (if no doses were missed), early or late missing (if missing the first dose during the first month of observation or later). The occurrence of clinical relapses and the annualized relapse rate (ARR) were prospectively recorded. Results: Adherence was 95.0 +/- 9.0%. Early missing (n = 17, 14.9%) was more likely to be associated with the occurrence of a clinical relapse (OR = 4.155; p = 0.018), but not late missing (n = 54, 47.4%) (OR = 1.454; p = 0.408), as compared to fully adherent (n = 43, 37.7%). Adherence was lower in early missing, as compared to late missing (p < 0.001). The ARR was higher in early missing, as compared to late missing and to fully adherent (p < 0.001). Conclusion: MS subjects missing an injection early presented lower adherence, and a fourfold chance of having a relapse, suggesting a simple way to assess and categorize adherence in a clinical, real-life setting, where lack of time often prevents more thorough evaluations

We thank Bifulco [1] for his interest in reading our article and his time in writing his comments on our work [2]. Our response to his concerns are as follows: The diseases studies in the papers that we cited in our Review on the Triangle of Death, and also others we did not include because they did not meet the inclusion criteria (Scopus, etc.), have a long period of latency. Environmental exposure related diseases require a long time before a diagnosis occurs. Diagnosis is made when the diseases ascertained, but latency refers to the length of time it takes from being exposed until when the disease becomes apparent in a clinical examination. Latency can be as short as 10 years or as long as 50, but the average length of latency for the diseases we studied is about 20 years between exposure and diagnosis (average for malignant mesothelioma is 35 to 40 years between exposure and diagnosis). The application of genetics to disease susceptibility moves away from the clinic towards the population, that integrated with the observational methods of epidemiology can potentially support more effective public health measures. The majority of genetic variants or single nucleotide polymorphisms in the human genome are of low penetrance, also for genes involved in metabolism of environmental chemicals, immunity, lipid metabolism, and hemostasis among others. The high prevalence of these single nucleotide polymorphisms means that, despite the low penetrance, they could provide a significant contribution to population disease burden. Exposure-disease associations and the interplay with genetic susceptibility requires further fundamental knowledge and studies on genetic variation, environment, lifestyle, and chronic disease, that are pivotal to provide insights into disease etiology at the population level. In alignment with this vision, Prof. Bifulco reports: “In my opinion, despite preliminary scientific studies suggest a link between hazardous exposure from toxic wastes and cancer occurrence [4], to definitively clarify this point further extensive and analytical studies are required”. Indeed, Barba et al. [3] conclude that currently available evidence suffers from limitations mainly due to study design, lack of consideration of confounders and quality of the exposure data. Despite all the sufferings and the concerns that the many issues and implications linked to the Land of Fires raise, it still provides an invaluable opportunity for research. The characterization of pollution types and sources would support effective and targeted measures to eliminate and reduce associated health risks, contributing to improved health outcomes for the population.

Introduction: Epidemiological studies report a 60-70% reduced risk of Parkinson's disease (PD) in smokers as compared to non-smokers. However, relationships between former smoking and PD have been poorly investigated. Methods: We recruited 116 de novo PD subjects, and investigated current, former and never smoking, and reasons for smoking cessation among former smokers. Two hundred and thirty-two controls were matched by Propensity Score. Results: PD subjects and controls were found to be current smokers (7.7 vs. 39.6%), former smokers (43.9 vs. 6.5%) and never smokers (48.2 vs. 53.9%). Logistic regression showed that current smokers were less likely to have PD (p

Background: Uric acid (UA) is a strong natural scavenger of reactive oxygen and nitrogen species, with evidence of possible use in the treatment of animal models of multiple sclerosis (MS). Consequently, serum UA has gained much attention as a possible biomarker of MS. We aim to investigate differences in serum UA levels between MS subjects and controls and evaluate possible relationships of UA with MS clinical features. Methods: We recruited relapsing-remitting and secondary progressive MS subjects and healthy controls and measured their serum UA levels. We excluded subjects presenting concomitant conditions affecting UA levels. Results: MS subjects (n=362) and controls (n=181) were recruited by propensity score matching (PSM). Statistical analyses were corrected for age, gender, and renal function. MS subjects presented significantly lower serum UA levels than controls (analysis of variance, p=0.014, adjusted r2=0.3036). Linear regression analysis showed a relationship between UA levels and disease duration (p

OBJECTIVES AND METHOD—The relation between body sway recorded through a stabilometric platform and the subjective report of steadiness was studied in 20 young and 20 elderly subjects and 20 neuropathic and 20parkinsonian patients standing upright. The trials were performed under two stances (feet apart, feet together) and two visual conditions (eyes open, eyes closed). At the end of each trial, subjects scored their performance on a scale from 10 (complete steadiness) to 0(fall). RESULTS—In all subjects, independently of the stance conditions, the larger the body sway the smaller the reported score. The function best fitting this relation was linear when sway was expressed on a logarithmic scale. The scoring reproducibility proved high both within and across subjects. Despite the different body sways and scores recorded under the different visual and postural conditions (eyes closed >eyes open, feet together>feet apart) in all groups of subjects and patients, the slopes of the relations between sway and score were broadly superimposable. In the normal subjects, the scores were slightly higher during eyes open than eyes closed trials for corresponding body sways. This was interpreted as a sign of perception of greater stability when vision was allowed. Parkinsonian patients swayed to a similar extent as normal subjects, and their scores were accordingly similar, both with eyes open and eyes closed. Neuropathic patients swayed to a larger extent than normal subjects, and their scores were matched appropriately. Although the slope of their relation with eyes closed was not different from that of normal subjects, with eyes open it was steeper and similar to that with eyes closed, suggesting that these patients did not feel more stable when they could take advantage of vision. CONCLUSIONS—The subjective evaluation of body sway, irrespective of stance condition, age, neuropathy, and basal ganglia disease, reflects the actual sway, and is inversely proportional to the logarithm of the sway value. The remarkable similarity of the relation between score and sway across the various groups of subjects with eyes closed indicates a common mode of sway evaluation, possibly based on integration of several sensory inputs. All groups except neuropathic patients seem to take advantage of the redundancy of the inputs. Basal ganglia integrity does not seem to have a role in the evaluation of sway.