Role of micronutrients in the symptoms of fibromyalgia: a review of the literature and analysis of an Italian female sample.

OBJECTIVE: Fibromyalgia (FM) is a multifactorial disease characterized principally by chronic, widespread pain impairing a patient's quality of life. The management of FM requires a multidisciplinary approach that combines pharmacological and non-pharmacological strategies. Growing evidence suggests a potential beneficial role of micronutrients such as minerals and vitamins. Overall, the role of these supplements remains controversial, but clinical trials on vitamin D, vitamin B12, magnesium, and iron supplementation seem to provide promising results. The aim of this study was to investigate their role in an Italian female sample. SUBJECTS AND METHODS: An exploratory cross-sectional study was done to assess the association of selected micronutrients with symptoms of FM by using the Fibromyalgia Impact Questionnaire (FIQ) in twenty consecutive female patients with FM. A literature review was also conducted. RESULTS: FIQ results revealed that vitamin D and magnesium deficiency appear to play a role in FM symptoms, mainly in physical function and stiffness. From the literature review, only two studies investigating the role of micronutrients in FM were retrieved. CONCLUSIONS: Screening for micronutrient deficiencies in FM patients and supplementing them when levels are low might help counteract FM symptoms.

Incessant pericarditis following the second dose of SARS-CoV-2 mRNA vaccine successfully treated with anakinra: a case report.

Background: The SARS-CoV-2 pandemic has led to the development of the first mRNA vaccines used in humans. These vaccines are well tolerated, safe, and highly effective; however, post-marketing surveillance is revealing potential rare adverse effects. We report a case of incessant pericarditis following administration of the second dose of mRNA-1273 SARS-CoV-2 vaccine, unresponsive to conventional therapy, and successfully treated with anakinra. Case summary: A 30-year-old man presented to the Emergency Department for incessant pericarditis unresponsive to evacuative pericardiocentesis and conventional first-line anti-inflammatory therapy. Given the typical 'inflammatory phenotype' clinically characterized by fever, C-reactive protein (CRP) elevation, and leucocytosis, we decided, in agreement with the rheumatologist team, to avoid glucocorticoid and to administer anakinra. A sudden clinical and echocardiographic improvement was observed, with complete resolution of the symptoms and of the pericardial effusion; similarly, CRP values progressively decreased. The patient was discharged at home; no recurrences of pericarditis were described at clinical and instrumental follow-up made 3 months later. Discussion: Several cases of pericarditis have been described in patients who received the COVID-19 vaccination, especially with the mRNA vaccine that can induce a non-adaptive immunity response against the viral spike protein, triggering cardiac damage for a molecular mimicry mechanism; however, defined pathogenesis of pericarditis associated with mRNA vaccine is still missing. The clinical scenario described is characterized by the typical 'inflammatory phenotype', triggered by a disproportionate and uncontrolled activation of the inflammasome based on an interleukin-1 (IL-1) overproduction. We administered anakinra, an IL-1 blocking drug, with a sharp clinical, echocardiographic and laboratoristic improvement. The complete response observed in this case suggests that vaccine-related pericarditis could be triggered by an auto-inflammatory pathway based on IL-1 overproduction. Further research is, therefore, warranted to determine the mechanisms by which the mRNA vaccine may cause pericarditis in order to choose the most targeted therapy.

Levosimendan for acute right heart failure in COVID-19: another arrow in our quiver?

OBJECTIVE: SARS-CoV-2 infection is associated with a higher risk of acute right heart failure (RHF) due to primary right ventricle (RV) dilation and systemic inflammatory response, which in turn lead to microvascular and cardiomyocytes dysfunction, local hypoxia and multi-organ failure. In this clinical setting, levosimendan could be a viable therapy thanks to its right-heart tropism and its additional pleiotropic properties. CASE REPORT: We present the case of a 72 years-old man with positive nasopharyngeal swab for SARS-CoV-2 infection, mild pulmonary involvement and clinical signs of new-onset RHF. We started a 12-hour levosimendan cycle to improve RV performance and reduce cardiac filling pressures. RESULTS: We obtained a net clinical benefit in terms of acute RHF-related signs and symptoms, progressive renal and liver function improvement and concomitant reduction of high-sensitivity C-Reactive Protein and Interleukin-6 (IL-6) levels. CONCLUSIONS: Acute RHF during SARS-CoV-2 infection could be related to a convergent widespread systemic inflammatory response. Thanks to its anti-inflammatory and anti-remodeling properties, levosimendan might represent a viable therapy in this clinical setting, contributing to the dampening of the inflammatory response.

An unusual case of death using a compacting machine.

ABSTRACT: In the large series of forensic injury, death from accidental me-chanical asphyxiation in adults is rare and is usually secondary to suffocation, aspiration, strangulation caused by entrapment of clothing in machinery (deaths at work) or asphyxiation in the course of erotic maneuvers. Compression asphyxia is a form of violent mechanical asphyxia in which the asphyxiated insult is produced by means of a compression and constriction mechanism of the thoracic cage. The authors report an unusual case of asphyxiated death from chest com-pression resulting from the action of a compacting machine, which occurred in a person who had fallen asleep in a waste bin.

Kv4 channel expression and kinetics in GABAergic and non-GABAergic rNST neurons.

The rostral nucleus of the solitary tract (rNST) serves as the first central relay in the gustatory system. In addition to synaptic interactions, central processing is also influenced by the ion channel composition of individual neurons. For example, voltage-gated K+ channels such as outward K+ current (IA) can modify the integrative properties of neurons. IA currents are prevalent in rNST projection cells but are also found to a lesser extent in GABAergic interneurons. However, characterization of the kinetic properties of IA, the molecular basis of these currents, as well as the consequences of IA on spiking properties of identified rNST cells is lacking. Here, we show that IA in rNST GABAergic (G+) and non-GABAergic (G-) neurons share a common molecular basis. In both cell types, there was a reduction in IA following treatment with the specific Kv4 channel blocker AmmTx3. However, the kinetics of activation and inactivation of IA in the two cell types were different with G- neurons having significantly more negative half-maximal activation and inactivation values. Likewise, under current clamp, G- cells had significantly longer delays to spike initiation in response to a depolarizing stimulus preceded by a hyperpolarizing prepulse. Computational modeling and dynamic clamp suggest that differences in the activation half-maximum may account for the differences in delay. We further observed evidence for a window current under both voltage clamp and current clamp protocols. We speculate that the location of Kv4.3 channels on dendrites, together with a window current for IA at rest, serves to regulate excitatory afferent inputs.NEW & NOTEWORTHY Here, we demonstrate that the transient outward K+ current IA occurs in both GABAergic and non-GABAergic neurons via Kv4.3 channels in the rostral (gustatory) solitary nucleus. Although found in both cell types, IA is more prevalent in non-GABAergic cells; a larger conductance at more negative potentials leads to a greater impact on spike initiation compared with GABAergic neurons. An IA window current further suggests that IA can regulate excitatory afferent input to the nucleus.

Diabetes Remission and Relapse After Bariatric Surgery: a Nationwide Population-Based Study.

PURPOSE: The long-term impact of bariatric surgery on the remission of type 2 diabetes (T2DM) remains to be clarified through large nationally representative cohorts. The objectives were to determine the incidence of T2DM remission and relapse after bariatric surgery, to determine the factors associated with remission and to establish a profile for patients at risk for relapse. MATERIALS AND METHODS: We conducted a population-based cohort study using data from the French national health insurance database (Systeme national des données de santé [SNDS]). We had access to exhaustive regional data between 2013 and 2017 and to a national representative sample of the French population (EGB) from 2008 to 2018. Patients were included if they were adults and diabetics with incidental bariatric surgery. RESULTS: This study shows that 50% of patients are in remission from diabetes after bariatric surgery within a median of 2 to 4 months. Diabetes relapse was observed in 13-20% within 10 years. The factors favouring remission already described were noted (non-insulin-dependent diabetes) and original factors were also identified, in particular the advantage of bypass surgery over sleeve gastrectomy, with more remissions and fewer relapses. CONCLUSION: This study highlights a 50% prevalence of remission and a low prevalence of relapse. There are non-modifiable risk factors for remission and relapse (characteristics of diabetes, age, lipid-lowering therapy) and modifiable factors (type of surgery). Identifying these factors is essential for optimal management of patients. Additional data are essential to confirm the results of our analysis of the factors associated with relapse.

Bevacizumab as maintenance treatment in BRCA mutated patients with advanced ovarian cancer: A large, retrospective, multicenter case-control study.

OBJECTIVE: The aim of this study was to investigate the correlation between BRCA mutational status and response to bevacizumab in a large advanced ovarian cancer (AOC) series. METHODS: This is a multicenter, retrospective case-control study including upfront AOC treated between January 2015 and June 2019. The main inclusion criteria were: having received three weekly carboplatin-paclitaxel as first-line treatment, with or without Bevacizumab maintenance, knowledge of the BRCA mutational status. RESULTS: Overall, 441 patients were included; 183 (41.5%) patients received bevacizumab (Cases), and 258 (58.5%) did not receive it (Controls). The BRCA mutated patients (BRCAmut) were 58 (39%) in the Cases group and 90 (34.9%) in the Controls group (p = .77). Patients who received bevacizumab had a significant 4-months increase in median progression free survival (mPFS: 21 vs. 17 months, p = .033). Concerning BRCAmut patients, no differences were shown between those who received bevacizumab or not in terms of mPFS (24 vs. 22 months, p = .3). Conversely, in BRCA wild-type (BRCAwt) population bevacizumab administration significantly prolonged mPFS (20 vs 15 months, p = .019). At multivariate analysis, independent factors of prolonged PFS were BRCA status (OR = 0.60), having received PDS (OR = 0.69), and complete cytoreduction (OR = 0.50), but not the bevacizumab administration (OR = 0.83, p = .22). CONCLUSIONS: No evidence of oncological benefit in terms of PFS and OS related to bevacizumab maintenance therapy was found in BRCAmut patients. Differently, BRCAwt patients seem to benefit from antiangiogenic treatment in terms of mPFS.

Salvage lymphadenectomy in recurrent ovarian cancer patients: Analysis of clinical outcome and BRCA1/2 gene mutational status.

OBJECTIVE: This study is aimed to analyze the clinical outcome of recurrent ovarian cancer patients bearing isolated lymph-node recurrence (ILNR) who underwent salvage lymphadenectomy (SL). The prognostic role of clinicopathological variables and the mutational status of BRCA1/2 have also been investigated. METHODS: This retrospective, single-institutional study included women with platinum-sensitive lymph node recurrence underwent to SL between June 2008 and June 2018. Univariate and multivariate analysis was performed to evaluate the impact of clinical parameters, and BRCA1/2 mutational status on post salvage lymphadenectomy progression-free survival (PSL-PFS). RESULTS: As of June 2019, the median follow-up after SL was 30 months, and the relapse has been documented in 48 (56.5%) patients. In the whole series, the median PSL-PFS was 21 months, and the 3-year PSL-PFS was 36.7%. The median PSL-PFS, according to patients with ILNR (N = 71) versus patients with lymph-nodes and other sites of disease (N = 14), was 27 months versus 12 months, respectively. Univariate analysis of variables conditioning PSL-PFS showed that platinum-free interval (PFI) ≥12 months, normal Ca125 serum levels, and number of metastatic lymph-nodes ≤3 played a statistically significant favorable role. In multivariate analysis, PFI duration ≥12 months and the number of metastatic lymph nodes ≤3 were shown to keep their favorable, independent prognostic value on PSL-PFS. CONCLUSIONS: In the context of SL, the patients with long PFI and low metastatic lymph node numbers at ILNR diagnosis have the best outcome. The BRCA mutational status seems not associated with clinical variables and PSL-PFS, differently from other sites of disease in ROC patients.

Carboplatin-paclitaxel compared to Carboplatin-Paclitaxel-Bevacizumab in advanced or recurrent endometrial cancer: MITO END-2 - A randomized phase II trial.

OBJECTIVE: Increased Vascular Endothelial Growth Factor Receptor (VEGF) expression in endometrial cancer (EC) is associated with a poor prognosis. Preliminary clinical data reported Bevacizumab effectiveness in EC both as single agent and in combination with chemotherapy. METHODS: In a phase II trial, patients with advanced (FIGO stage III-IV) or recurrent EC were randomized to receive Carboplatin-Paclitaxel standard dose for 6-8 cycles vs Carboplatin-Paclitaxel and Bevacizumab 15 mg/kg in combination with chemotherapy and maintenance until disease progression or unacceptable toxicity. The primary endpoint was progression free survival (PFS). RESULTS: 108 patients were randomized; PFS (10.5 vs 13.7 months, HR 0.84 p = 0.43), overall response rate (ORR 53.1% vs 74.4%) and overall survival (OS) (29.7 vs 40.0 months, HR 0.71 p = 0.24) resulted in a non-significant increase in Bevacizumab treated patients. The PFS increase became significant when an exploratory analysis with the Breslow test was used. Moreover, patients treated with Bevacizumab experienced a significant increase in 6-month disease control rate (70.4% vs 90.7%). Cardiovascular events were more frequent in the experimental arm ("de novo" grade ≥2 hypertension 21% vs 0% and grade ≥2 thromboembolic events 11% vs 2% in the Bevacizumab vs standard treatment arm, respectively). CONCLUSIONS: Bevacizumab combined with chemotherapy in the treatment of advanced/recurrent EC failed to demonstrate a significant increase in PFS in the MITO END-2 trial. Nevertheless, these preliminary data suggests some effectiveness of the antiangiogenic agent which merits further exploration in a larger population with a better molecular characterization.

Vitamin D receptor expression and acid sphingomyelinase activity in prefrontal region of a learning animal model.

Contextual fear conditioning (CFC) paradigm is routinely used to study fear-based learning in animals and it provides a useful model for understanding fear and anxiety in human. In the present study, such model was used following the previously established CFC protocol, and immunohistochemistry, enzymatic activity and western blotting analysis approaches were used to identify the expression of acid sphingomyelinase (aSMase) and vitamin D receptor (VDR) in prefrontal region brain of rat. Results revealed an increase of aSMase activity in conditioned rats, suggesting an apoptotic condition in such animals. In addition, an increase of density and organization of axonal neurofilaments and of VDR expression has been observed in brain of conditioned rats, supporting an induction of growth and organization of new neurons in prefrontal regions, whose contribution to various aspects of contextual fear learning is still largely unknown.

Global lower limb muscle coactivation during walking at different speeds: Relationship between spatio-temporal, kinematic, kinetic, and energetic parameters.

Muscle coactivation is the mechanism that regulates the simultaneous activity of antagonist muscles around the same joint. During walking, muscle joint coactivation varies within the gait cycle according to the functional role of the lower limb joints. In the present study, we used a time-varying multi-muscle coactivation function (TMCf) with the aim of investigating the coactivation of 12 lower limb muscles and its relationship with the gait cycle, gait speed (low, self-selected, and fast), ground reaction force, gait variability, and mechanical energy consumption, and recovery in a sample of 20 healthy subjects. Results show that the TMCf is speed dependent and highly repeatable within and between subjects, similar to the vertical force profile, and negatively correlated with energy recovery and positively correlated with both energy consumption and balance-related gait parameters. These findings suggest that the global lower limb coactivation behavior could be a useful measure of the motor control strategy, limb stiffness, postural stability, energy efficiency optimization, and several aspects in pathological conditions.

Effect of Restraining the Base of Support on the Other Biomechanical Features in Patients with Cerebellar Ataxia.

This study aimed to analyze the biomechanical consequences of reducing the base of support in patients with ataxia. Specifically, we evaluated the spatio-temporal parameters, upper- and lower-body kinematics, muscle co-activation, and energy recovery and expenditure. The gaits of 13 patients were recorded using a motion analysis system in unperturbed and perturbed walking conditions. In the latter condition, patients had to walk using the same step width and speed of healthy controls. The perturbed walking condition featured reduced gait speed, step length, hip and knee range of motion, and energy recovery and increased double support duration, gait variability, trunk oscillation, and ankle joint muscle co-activation. Narrowing the base of support increased gait instability (e.g., gait variability and trunk oscillations) and induced patients to further use alternative compensatory mechanisms to maintain dynamic balance at the expense of a reduced ability to recover mechanical energy. A widened step width gait is a global strategy employed by patients to increase dynamic stability, reduce the need for further compensatory mechanisms, and thus recover mechanical energy. Our findings suggest that rehabilitative treatment should more specifically focus on step width training.

Laser procedure for female urinary stress incontinence: A review of the literature.

INTRODUCTION: There is increasing interest in noninvasive treatment of female stress urinary incontinence (SUI), including a vaginal laser procedure. In view of a lack of data on this technique, we conducted a non-systematic review of the literature. METHODS: We reviewed studies concerning the laser treatment of SUI from PubMed, Medline, the Cochrane Library and Web of Science. Study design, outcome measure, number of participants, procedural complications and results were analyzed. RESULTS: The use of laser treatment of female SUI has been described in 7 prospective, single-center and non-comparative (no control group) studies, all of which used an erbium YAG or a CO2 laser in thermal non-ablative treatment. Primary outcome was ICIQ-UI-SF score in six studies, and pad tests in one study. Follow-up ranged from 5 to 36months. Improvement rates ranged from 62% to 78%. No major adverse events were noted. Minor side effects included sensation of warmth, increased vaginal discharge and transient urge urinary incontinence. CONCLUSION: The efficacy of vaginal laser treatment of SUI has not been assessed in comparative studies. More rigorous and adequately powered trials are required to assess the relative benefits and adverse event profile of laser treatment of SUI, as compared with other minimally invasive procedures.

Diagnostic accuracy of MDCT in the evaluation of patients with peritoneal carcinomatosis from ovarian cancer: is delayed enhanced phase really effective?

OBJECTIVE: To assess the diagnostic accuracy of delayed enhanced phase in addition to portal enhanced phase in MDCT imaging for depicting peritoneal carcinomatosis (PC) implants in patients with ovarian cancer. PATIENTS AND METHODS: We retrospectively reviewed double-phase, portal enhanced phase (PEP) and delayed enhanced phase (DEP), MDCT-examinations of 40 patients with clinical suspicion of recurrent PC from histopathologically-proven ovarian cancer, previously treated with both cytoreductive surgery and adjuvant/neoadjuvant chemotherapy. Image assessment was performed by three independent blinded readers (2 experienced and 1 less-experienced radiologists) in 3 different reading sessions: PEP (set A), DEP (set B), and PVP + DEP (set C). All CT-images were qualitatively assessed on the basis of the location of the lesion (based on Sugarbaker scheme), presence (indicating a confidence level for the diagnosis of PC), size and pattern. Reference standard both for detection and exclusion of PC was the evaluation of double-phase MDCT exams performed by two experienced readers in consensus, knowing clinical and laboratoristic parameters as well as previous and subsequent imaging (follow-up minimum of 12 months). Sensitivity, specificity, PPV, NPV and diagnostic accuracy of each reader for each reading session were calculated and compared. A subgroup analysis based on lesion pattern was also performed. RESULTS: On a total of 507 abdominal-pelvic sites evaluated, PC was found in 182 regions (35.9%). When considering experienced radiologists, no statistically significant differences (p>0.05) were found between the different sets of images. The analysis by less-experienced radiologist showed lower statistical results, which significantly improved when both PEP and DEP were evaluated. In the subgroup analysis, DEP showed significantly higher statistical results in the case of micronodular patterns. CONCLUSIONS: Our results indicate that the CT-acquisition protocol in patients with ovarian cancer for tumor staging should be based on portal phase alone, with a significant radiation dose reduction, whereas the addition of delayed phase images is useful for less-experienced readers.

Functional characterization of biodegradable nanoparticles as antigen delivery system.

BACKGROUND: Peptide based vaccines may suffer from limited stability and inefficient delivery to professional antigen-presenting cells (APCs), such as dendritic cells (DCs). In order to overcome such limitations, several types of biodegradable nanoparticles (NPs) have been developed as carrier system for antigens. The present study describes for the first time the extensive biological characterization of cationic NPs made of poly (D,L-lactide-co-glycolide) (PLGA) and polyethylenimine (PLGA/PEI) as delivery system for protein/peptide antigens, with potential in therapeutic cancer vaccine development. RESULTS: Flow cytometry as well as confocal laser scanning microscopy (CLSM) showed that PLGA/PEI NPs are more readily taken up than PLGA NPs by both human CD14(+) monocytes and mouse Hepa 1-6 hepatoma cell line. No signs of toxicity were observed in either cellular setting. Sequential image acquisition by TEM showed an intracellular apical localization for PLGA NPs and a perinuclear localization for PLGA/PEI NPs. Both NPs showed a clathrin-dependent as well as a caveolin-dependent internalization pathway and, once in the cells, they formed multivesicular endosomes (MVE). Finally, an ex vivo priming experiment showed that PLGA/PEI NPs are comparable to PLGA NPs in delivering a non-self antigen (i.e., ovalbumin - OVA) to immature dendritic cells (imDCs), which matured and induced autologous naïve CD4(+) T cells to differentiate to memory (i.e., central memory and effector memory) cells. Such a differentiation was associated with a Th1 phenotype suggesting a downstream activation and amplification of a CD8(+) T cell cytotoxic response. The same OVA antigen in a soluble form was unable to induce maturation of DCs, indicating that both NP formulations provided an intrinsic adjuvanting effect combined to efficient antigen delivery. CONCLUSIONS: Our study represents the first report on side-by-side comparison of PLGA and PLGA/PEI NPs as strategy for protein antigen delivery. PLGA/PEI NPs are superior for cellular uptake and antigen delivery as compared to PLGA NPs. Such an evidence suggests their great potential value for vaccine development, including therapeutic cancer vaccines.

Clinical predictors of fever in stroke patients: relevance of nasogastric tube.

OBJECTIVES: Fever frequently occurs in stroke patients and worsens their prognosis. However, only few studies have assessed the determinants of fever in acute stroke, and no study has specifically addressed the possible prediction of the development of fever. MATERIALS AND METHODS: This investigation included 536 patients with acute stroke and a body temperature <=37°C during the first 24 h of stay. Ninety-two of them (17.2%) subsequently developed fever (defined as a temperature >=37.5°C starting after 24 h). Among the clinical variables available during the first 24 h from admission, those predictive of the subsequent appearance of fever were searched for. One hundred further patients had a temperature >37°C during the first 24 h. RESULTS: In univariate analysis, many variables were predictive of the subsequent development of fever, but in multivariate analysis, only the following four predictors remained significant (odds ratio [95% confidence interval], P value): nasogastric tube (4.0 [2.2-7.4], <0.0001), atrial fibrillation (2.3 [1.4-3.8], 0.001), total anterior circulation syndrome (2.0 [1.2-3.5], 0.01), and urinary catheter (1.9 [1.1-3.3], 0.01). Among the 52 (9.7%) patients with three or four predictors, 31 (59.6%) subsequently developed fever. In addition, the factors independently associated with a temperature >37°C during the first 24 h were as follows: National Institutes of Health Stroke Scale (P < 0.0001), hemorrhagic stroke (P = 0.0008), atrial fibrillation (P = 0.002), and total parenteral nutrition (P = 0.03). CONCLUSIONS: In patients with acute stroke, four clinical variables were found to be independently associated with the risk of developing fever and, of them, nasogastric tube was the strongest and most significant one.

Total Mercury in Carnivorous Fish from Brazilian Southeast.

Total mercury concentrations were determined by atomic absorption spectrometry in muscle tissue of two commercially important species of carnivorous fishes croaker (Micropogonias furnieri) and cutlassfish (Trichiurus lepturus) caught in Itaipu estuary, Rio de Janeiro. In this study, whitemouth croaker presented more mercury than Atlantic cutlassfish. Bioaccumulation differences can be explained by the biological behavior of juveniles whitemouth croaker, that remain in the estuary up to maturity, which makes them good indicators of local environmental impacts (0.110 mg Kg(-1) HgT). It also can be explained by differences in nutritional requirements between the different life stages of two species. The analysis showed the presence of low levels of the metal. However, our results suggest a possible risk to human health, depending on the level of fish consumption.

Locomotor patterns in cerebellar ataxia.

Several studies have demonstrated how cerebellar ataxia (CA) affects gait, resulting in deficits in multijoint coordination and stability. Nevertheless, how lesions of cerebellum influence the locomotor muscle pattern generation is still unclear. To better understand the effects of CA on locomotor output, here we investigated the idiosyncratic features of the spatiotemporal structure of leg muscle activity and impairments in the biomechanics of CA gait. To this end, we recorded the electromyographic (EMG) activity of 12 unilateral lower limb muscles and analyzed kinematic and kinetic parameters of 19 ataxic patients and 20 age-matched healthy subjects during overground walking. Neuromuscular control of gait in CA was characterized by a considerable widening of EMG bursts and significant temporal shifts in the center of activity due to overall enhanced muscle activation between late swing and mid-stance. Patients also demonstrated significant changes in the intersegmental coordination, an abnormal transient in the vertical ground reaction force and instability of limb loading at heel strike. The observed abnormalities in EMG patterns and foot loading correlated with the severity of pathology [International Cooperative Ataxia Rating Scale (ICARS), a clinical ataxia scale] and the changes in the biomechanical output. The findings provide new insights into the physiological role of cerebellum in optimizing the duration of muscle activity bursts and the control of appropriate foot loading during locomotion.