Effect of Exoskeleton-Assisted Rehabilitation Over Prefrontal Cortex in Multiple Sclerosis Patients: A Neuroimaging Pilot Study.

Application of a passive and fully articulated exoskeleton, called Human Body Posturizer (HBP), has been demonstrated to improve mobility, response accuracy and ambulation in multiple sclerosis (MS) patients. By using functional magnetic imaging (fMRI) during a visuomotor discrimination task, we performed a pilot study to evaluate the effect of HBP over the neural correlates of motor and cognitive functions which are typically impaired in MS patients. Specifically, we tested the effect of a 6-week multidisciplinary rehabilitation intervention on two groups of MS patients: a control group who followed a standard physiotherapeutic rehabilitation protocol, and an experimental group who used the HBP during physical exercises in addition to the standard protocol. We found that, after treatment, the experimental group exhibited a significant lower activity (as compared to the control group) in the inferior frontal gyrus. This post-treatment activity reduction can be explained as a retour to a normal range, being the amount of iFg activity observed in the experimental patients very similar to that observed in healthy subjects. These findings indicate that the use of HBP during rehabilitation intervention normalizes the prefrontal activity, mitigating the cortical hyperactivity associated to MS.

Outbreak of hepatitis C virus infections originating from a breach in safe injection practices before contrast-enhanced computed tomography scanning.

Four patients who underwent contrast-enhanced computed tomography (CT) scanning were infected with hepatitis C virus from a contaminated multi-dose vial of NaCl. The outbreak likely occurred due to a breach in safe injection practices, resulting in contamination of the vial. Not all patients exposed to the same vial were infected. The uneven distribution of infections could be attributed to a stochastic effect of a low infectious dose. This implies that outbreak investigations need to be extended to all patients scheduled before and after the first identified infected patient to confirm or rule out nosocomial transmission.

Dielectric properties of healthy and diabetic alloxan-induced lenses in rabbits.

The dielectric properties of the eye lens were studied for healthy and alloxane-induced diabetic rabbits in the frequency range from 500 Hz to 100 kHz electric field and temperatures from 25 to 50 °C. In the full temperature range, the average relative permittivity and dielectric loss values for a healthy lens are lower than those recorded for diabetic tissue. Dielectric relaxation of polar amino acids on the alpha-crystallin surface with a characteristic frequency of 7 kHz in the range of 25-50 °C for healthy and diabetic samples is accompanied by the activation energy of proton conductivity with an average values of 33 and 39 kJ mol-1, respectively. The permittivity decrement, which characterizes the size of the dielectric dispersion with a central relaxation time of 0.023 ms for a diabetic sample, is more than twice as high as for a healthy sample. Measurements on the rabbit eye lens were carried out at ambient temperature above and below the physiological range, since these conditions provide an appropriate pattern of dielectric behavior for the diagnosis of clinical dysfunction of the human lens.

Sensorized assessment of bilateral hand movements in patients with stroke driven by rhythmic auditory or visual-auditory stimulation.

There is a growing body of literature about the efficacy in neurorehabilitation of the devices providing rhythmic auditory stimulations or visual-auditory stimulations, such as videogames, for guiding the patients' movements. Despite being presented as tools able to motivate patients, their efficacy was not been proven yet, probably due to the limited knowledge about the factors influencing the capability of patients to move the upper limbs following an external stimulus. In this study, we used a marker less system based on two infrared sensors to assess the kinematics of up and down in-phase and anti-phase bilateral hand oscillations synchronized or not with an external stimulus. A group of stroke survivors, one of age-matched healthy subjects and one of young healthy subjects were tested in three conditions: no stimulus, auditory stimulus, and video-auditory stimulus. Our results showed significant negative effects of visual-auditory stimulus in the frequency of movements (p = 0.001), and of auditory stimulus in their fluidity (p = 0.013). These results are conceivably related to the attentional overload required during the execution of bilateral movements driven by an external stimulus. However, a positive effect of external stimulus was found in increasing the range of movements of the less functional hand in all subjects (p = 0.023). These findings highlight as the type of stimulus may play a crucial role in the patient's performance with respect to movements that are not-externally driven.

Effect of different music genres on gait patterns in Parkinson's disease.

The timing and size of repetitive, internally generated, automatic sequences of movements are particularly affected in Parkinson's disease. The most evident consequence of this deficit is the alteration of gait patterns, with a loss of rhythmicity, shorter steps, slower walking, and trunk instability. Several studies have highlighted a potential benefit of listening to music on the normalization of walking patterns. However, most of these studies investigated the effect of a single specific music. We hypothesized that different musical genres may induce different modifications of spatiotemporal parameters and trunk oscillations during walking. In this study, we enrolled healthy young subjects, healthy elderly, and patients with Parkinson's disease. They were asked to walk listening, by a wireless headset, one of six different music tracks (related to four different musical genres) while wearing an inertial measurement unit at pelvis level used to assess their walking patterns. The main effect of music tracks resulted statistically significant in all the gait parameters (p < 0.05), but for symmetry of lower trunk movements. This effect was independent by group. The only significant interaction between music and group, in fact, was found for pelvis obliquity range of motion (p = 0.019). Post hoc analyses showed as classical music reduced speed and trunk tilting (p < 0.01), whereas the range of pelvic obliquity movements in frontal plane were increased by rock, motivational, and heavy metal songs (p < 0.015). In conclusion, the gait patterns were altered by listening music depending by the musical genre, and these adaptations occurred similarly among the three groups, including patients with Parkinson's disease.

Prevalence and determinants of resistance mutations in HIV-1-infected patients exposed to integrase inhibitors in a large Italian cohort.

OBJECTIVES: The aim of the study was to analyse the prevalence of integrase resistance mutations in integrase strand transfer inhibitor (INSTI)-experienced HIV-1-infected patients and its predictors. METHODS: We selected HIV-1 integrase sequences from the Antiviral Response Cohort Analysis (ARCA) database, derived from INSTI-experienced patients between 2008 and 2017. Differences in the prevalence of resistance to raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG) were assessed by χ2 test and predictors of resistance were analysed by logistic regression. RESULTS: We included 462 genotypes from INSTI-exposed individuals: 356 'INSTI-failing' patients and 106 'previously INSTI-exposed' patients (obtained a median of 42 weeks after INSTI discontinuation [interquartile range (IQR) 17-110 weeks]). Overall, at least low-level resistance (LLR) to any INSTI (Stanford 8.5 algorithm) was detected in 198 (42.9%) cases. The most frequent INSTI resistance mutation was N155H, followed by Q148H/K/R, G140A/C/S, E138A/K/T and Y143C/H/R. Y143R and E138A were more prevalent in viral subtype B versus non-B [5.2 versus 1.5%, respectively (P = 0.04), and 3.1 versus 0%, respectively (P = 0.02)]. Overall, the Q148H/K/R plus G140A/C/S and/or E138A/K/T pattern, defining an intermediate level of resistance to DTG, was detected in 70 (15%) cases. Independent predictors of at least LLR to any INSTI were current use versus past use of INSTIs, a lower genotypic sensitivity score (GSS) for contemporary antiretroviral drugs used, and having an integrase sequence obtained in calendar year 2016 as compared to 2008-2009. CONCLUSIONS: The results support integrase resistance testing in INSTI-experienced patients. Emergence of INSTI resistance is facilitated by the reduced genetic barrier of the regimen as a consequence of resistance to companion drugs. However, INSTI resistance may become undetectable by standard population sequencing upon INSTI discontinuation.

Dolutegravir (DTG)-containing regimens after receiving raltegravir (RAL) or elvitegravir (EVG): Durability and virological response in a large Italian HIV drug resistance network (ARCA).

BACKGROUND: Dolutegravir (DTG) is a next-generation HIV integrase inhibitor (INI) with an increased genetic barrier to resistance with respect to raltegravir (RAL) or elvitegravir (EVG). Few data are available on the durability of DTG-containing regimens. OBJECTIVES: We aimed at investigating the duration of the DTG-containing regimen, the occurrence of an HIV-1 RNA blip, and factors associated with DTG virological response. STUDY DESIGN: From the Antiviral Response Cohort Analysis database, we selected 89 HIV-1-positive four-class-experienced subjects who started DTG after receiving RAL or EVG. Factors associated with durability and virological response were analysed by logistic regression. RESULTS: After a median duration of 18.8 [0.4-76.2] months, 79/89 (88.8%) subjects were still on DTG. All subjects remaining on DTG at the end of follow-up had undetectable HIV-1 RNA, compared to 5/10 subjects who discontinued DTG. DTG discontinuation was less frequent in patients who had experienced ≥10 regimens (HR 0.11, p = 0.040). The probability of having an HIV-1 RNA positive value at the last follow-up significantly increased in patients with non-B HIV-1 subtype (HR 5.77, p < .001) and significantly decreased in patients with CD4 nadir >200/µL (HR 0.29, p = 0.038), with more than 10 previous regimens (HR 0.27, p = 0.040), and who harbored virus with IN mutations (HR 0.12, p = 0.023) at DTG start. CONCLUSIONS: After previous exposure to first-generation INIs, treatment with DTG showed long durability and did not show virological rebound after virological suppression. Subjects infected with a non-B HIV-1 subtype had a greater risk of having detectable HIV-1 RNA at the last observation.

Post Soft Care: Italian implementation of a post-stroke checklist software for primary care and identification of unmet needs in community-dwelling patients.

The needs of community-dwelling stroke patients are often not fully addressed. The Global Stroke Community Advisory Panel had developed the Post Stroke Checklist (PSC) with the aim of standardizing long-term stroke assessment and consequently care of patients. PSC has been validated for UK and Singapore, and an Italian version has been proposed. The aim of this study is to assess the needs of community-dwelling Italian stroke patients using an online version of PSC. Secondary aim is to assess utility of PSC for patients and clinicians. The PSC was administered to a sample of 64 patients with stroke in Italy by general practioners. PSC is a questionnaire formed by 11 questions, each one covering a domain identified as important for patients' health. After administration of PSC, patient and clinician satisfaction with the PSC was assessed by a specific questionnaire. The PSC identified specific problems for patients related to a worsening from the last examination not evaluated by any specialist. The online PSC highlighted problems related to mood, (in 50% of sample), mobility (53.1%), spasticity (42.2%), and pain (37.5%). Both patients and clinicians provided good results about the utility of online PSC. The PSC was confirmed to be a useful tool for identifying the needs of community-dwelling patients with stroke. Particular attention should be deserved to problems related to mood, mobility, and hence participation to social life, pain, and spasticity. For taking into account these aspects, the online PSC can be a useful portable tool for clinicians.

Optimal efficacy of interferon-free HCV retreatment after protease inhibitor failure in real life.

OBJECTIVES: First-generation protease-inhibitors (PIs) have suboptimal efficacy in GT-1 patients with advanced liver disease, and patients experiencing treatment failure may require urgent retreatment. Our objective was to analyse the real-life efficacy of interferon (IFN)-free retreatment after PI-failure, and the role of genotypic-resistance-testing (GRT) in guiding retreatment choice. METHODS: In this multi-centre observational study, patients retreated with IFN-free regimens after first-generation PI-failure (telaprevir-boceprevir-simeprevir) were included. Sustained-virological-response (SVR) was evaluated at week 12 of follow-up. GRT was performed by population-sequencing. RESULTS: After PI-failure, 121 patients (cirrhotic=86.8%) were retreated following three different strategies: A) with 'GRT-guided' regimens (N=18); B) with 'AASLD/EASL recommended, not GRT-guided' regimens (N=72); C) with 'not recommended, not GRT-guided' regimens (N=31). Overall SVR rate was 91%, but all 18 patients treated with 'GRT-guided' regimens reached SVR (100%), despite heterogeneity in treatment duration, use of PI and ribavirin, versus 68/72 patients (94.4%) receiving 'AASLD/EASL recommended, not GRT-guided' regimens. SVR was strongly reduced (77.4%) among the 31 patients who received a 'not recommended, not GRT-guided regimen' (p <0.01). Among 37 patients retreated with a PI, SVR rate was 89.2% (33/37). Four GT-1a cirrhotic patients failed an option (C) simeprevir-containing treatment; three out of four had a baseline R155K NS3-RAS. All seven patients treated with paritaprevir-containing regimens reached SVR, regardless of treatment duration and performance of a baseline-GRT. CONCLUSION: Retreatment of PI-experienced patients can induce maximal SVR rates in real life. Baseline-GRT could help to optimize retreatment strategy, allowing PIs to be reconsidered when chosen after a RASs evaluation.

How to diagnose neuropathic pain? The contribution from clinical examination, pain questionnaires and diagnostic tests.

Patients with peripheral and central nervous system diseases may suffer from different types of pain, namely nociceptive, neuropathic and mixed pain. Although in some cases, the distinction between these types of pain is clinically evident, yet in some patients an accurate differential diagnosis requires dedicated clinical examination, screening questionnaires and diagnostic techniques some of which are available only in specialized pain centres. This review briefly addresses the currently agreed definitions of the different types of pain and shows how clinical examination, pain questionnaires and diagnostic tests can help the clinicians in identifying neuropathic pain.

Does outcome of neuropsychological treatment in patients with unilateral spatial neglect after stroke affect functional outcome?

BACKGROUND: Unilateral spatial neglect (USN) after stroke is associated to severe disability and to a poor rehabilitation outcome. However it is still unclear if a reduction of USN after a specific neurophsycological treatment could also favor the functional recovery. AIM: The first aim of this study was to determine if low responders to neuropsychological treatment of unilateral spatial neglect may have a worse functional prognosis for activities of daily living. The second aim was to investigate which variables can predict a low response to neuropsychological treatment. DESIGN: Observational study. SETTING: Neurorehabilitation hospital in Italy. POPULATION: Two hundred inpatients with the diagnosis of ischemic stroke were screened in this observational study. Inclusion criteria were: patients in subacute phase of first ischemic stroke in right hemisphere. Exclusion criteria were: presence of previous and/or other disabling pathologies, medical conditions contraindicating physical therapy. Data of 73 patients who performed neurorehabilitation and visual scanning training for reducing USN were analysed, while the remaining others were excluded for at least one of the following reasons: hemorrhagic lesions, presence of other chronic disabling pathologies, contraindications for therapy. METHODS: USN was evaluated using: Letter Cancellation Test, Barrage Test, Sentence Reading Test and Wundt-Jastrow Area Illusion Test. Barthel Index (BI), Beck Depression Inventory, and Canadian Neurological Scale were also administered. According to the aim of the study, forward binary logistic regressions were performed to evaluate the effects of different factors on functional recovery. RESULTS: Three factors were identified as predictors of low effectiveness in terms of BI-score: older age (odds ratio OR=9.882, P=0.002), severity of disease at admission (OR=12.594, P=0.002) and being low responders to neuropsychological treatment (OR=3.847, P=0.027). Further, the initial barrage score (OR=3.313, P=0.027) and the initial BI-score (OR=3.252, P=0.039) effectively predict the response to neuropsychological treatment. CONCLUSION: The outcome of the whole rehabilitation resulted affected by the outcome of neuropsychological treatment in patients with USN, being a low score at Barrage test at the beginning of therapy a negative predictor of USN recovery. CLINICAL REHABILITATION IMPACT: Patients with USN after stroke can benefit of a specific training for reducing USN also in terms of functional outcome. Further, the simple use of Barrage test could provide important prognostic information about recovery.

Video-game based therapy performed by children with cerebral palsy: a cross-over randomized controlled trial and a cross-sectional quantitative measure of physical activity.

BACKGROUND: Previous studies reported controversial results about the efficacy of video-game based therapy (VGT) in improving neurorehabilitation outcomes in children with cerebral palsy (CP). AIM: Primary aim was to investigate the effectiveness of VGT with respect to conventional therapy (CT) in improving upper limb motor outcomes in a group of children with CP. Secondary aim was to quantify if VGT leads children to perform a higher number of movements. DESIGN: A cross-over randomized controlled trial (RCT) for investigating the primary aim and a cross-sectional study for investigating the secondary aim of this study. SETTINGS: Outpatients. INCLUSION CRITERIA: clinical diagnosis of CP, age between 4 and 14 years, level of GMFC between I and IV. EXCLUSION CRITERIA: QI<35, severe comorbidities, incapacity to stand even with an external support. METHODS: Twenty-two children with CP (6.89±1.91-year old) were enrolled in a cross-over RCT with 16 sessions of VGT (using Xbox with Kinect device) and then 16 of CT or vice versa. Upper limb functioning was assessed using the Quality of Upper Extremities Skills Test (QUEST) and hand abilities using Abilhand-kids score. According to the secondary aim of this study a secondary cross-sectional study has been performed. Eight children with CP (6.50±1.60-year old) were enrolled into a trial in which five wireless triaxial accelerometers were positioned on their forearms, legs and trunk for quantifying the physical activity during VGT vs. CT. RESULTS: QUEST scores significantly improved only after VGT (P=0.003), and not after CT (P=0.056). The reverse occurred for Abilhand-kids scores (P=0.165 vs. P=0.013, respectively). Quantity of performed movements was three times higher in VGT than in CT (+198%, P=0.027). CONCLUSION: VGT resulted effective in improving the motor functions of upper limb extremities in children with CP, conceivably for the increased quantity of limb movements, but failed in improving the manual abilities for performing activities of daily living which benefited more from CT. CLINICAL REHABILITATION IMPACT: VGT performed using the X-Box with Kinect device could enhance the number of upper limb movements in children with CP during rehabilitation and in turn improving upper limb motor skills, but CT remained superior for improving performances in manual activities of daily living.

Skewed B cells in chronic hepatitis C virus infection maintain their ability to respond to virus-induced activation.

Chronic hepatitis C virus (HCV) infection is characterized by persistent B-cell activation, with enhanced differentiation and reduced proliferative ability. To assess the possible role of HCV in altering B-cell subset distribution, we examined ex vivo frequencies and B-cell inhibitory receptor expression in 37 chronic HCV-infected patients and 25 healthy donors (HD). In addition, we determined whether short-term exposure to culture-derived HCV (HCVcc) resulted in B-cell subset skewing and/or activation. There was a statistically significant increase in the frequencies of immature transitional, activated memory and tissue-like memory (TLM) B cells in HCV-infected patients compared with HD. We also found that the frequency of memory B cells correlated with serum HCV RNA levels. The proportion of B cells expressing the marker of exhaustion Fc receptor-like 4 (FcRL4) was generally low even though significantly higher in the patients' memory B-cell compartment compared with HD, and a positive correlation was found between the frequencies of the patients' TLM FcRL4+ B cells and serum alanine aminotransferase and histological activity index at liver biopsy. Exposure to cell-free HCVcc in vitro did not result in B-cell skewing but induced significant activation of naïve, TLM and resting memory B cells in HCV-infected patients but not in HD, in whom cell-associated virus was an absolute requirement for activation of memory B cells. These findings provide corroborative evidence in favour of significant B-cell subset skewing in chronic HCV infection and in addition show that expression of exhaustion markers in selected B-cell subsets does not impair virus-induced B-cell activation.

Assessment of waveform similarity in clinical gait data: the linear fit method.

The assessment of waveform similarity is a crucial issue in gait analysis for the comparison of kinematic or kinetic patterns with reference data. A typical scenario is in fact the comparison of a patient's gait pattern with a relevant physiological pattern. This study aims to propose and validate a simple method for the assessment of waveform similarity in terms of shape, amplitude, and offset. The method relies on the interpretation of these three parameters, obtained through a linear fit applied to the two data sets under comparison plotted one against the other after time normalization. The validity of this linear fit method was tested in terms of appropriateness (comparing real gait data of 34 patients with cerebrovascular accident with those of 15 healthy subjects), reliability, sensitivity, and specificity (applying a cluster analysis on the real data). Results showed for this method good appropriateness, 94.1% of sensitivity, 93.3% of specificity, and good reliability. The LFM resulted in a simple method suitable for analysing the waveform similarity in clinical gait analysis.

Can overestimation of walking ability increase the risk of falls in people in the subacute stage after stroke on their return home?

PURPOSE: Falls are common in patients who have had a stroke who return home after neurorehabilitation. Some studies have found that walking speed inversely correlates with the risk of falls. SCOPE: This study examined whether comparison between comfortable self-selected walking speed and maximum maintainable speed is informative with regard to the risk of falls in patients with stroke. METHODS: A prospective cohort study was performed with 75 ambulant stroke patients. At discharge, the Barthel Index score and performance at the 10-m and 6-min walking tests were assessed. Number of falls was recorded by telephone interview every two months for one year. Regression analysis was performed to identify factors that were related to the risk of falls. RESULTS: Using forward multiple linear regression, only the ratio between walking speeds on the 6-min and 10-m tests was linked to the number of falls in the year after discharge (R=-0.451, p<0.001, OR=0.046). Patients who chose a walking speed for short distances that was not maintainable long term fell more frequently. CONCLUSIONS: A discrepancy between short and long-term walking speed can help in identifying subjects in the subacute stage after stroke with an increased risk of suffering a fall.

Effect of Chêneau brace on postural balance in adolescent idiopathic scoliosis: a pilot study.

BACKGROUND: Adolescents with idiopathic scoliosis show a postural instability compared with healthy subjects. DESIGN TYPE. Case control study. SETTING: Outpatient clinic of the Complex Operative Unit of Physical Medicine and Rehabilitation of Policlinico Umberto I Hospital. POPULATION: Thirteen patients (11 females and 2 males, mean age 13.3±1.7 years, mean Cobb angle 32±9, median Risser sign 2) and thirteen healthy adolescents (8 females and 5 males, mean age: 13.0±1.6 years) as age-matched control group were enrolled. METHODS: Postural ability of the participants was assessed with stabilometry (under open eyes and closed eyes conditions), computing sway length, sway ellipse area, and sway velocities. Static and dynamic baropodometry (open eyes only) was used to measure the limb load, and to compute: walking speed, step length, step cadence and step width. The symmetry of left and right limb values was also investigated. RESULTS: Patient's group was characterized by significantly higher postural instability than control group (P<0.05) that decreased with brace in terms of limb load symmetry (-12% in eyes open condition), sway length (-12%), velocity in anteroposterior (-16%) and latero-lateral directions (-10%). Significant correlations were found between the changes occurred when wearing Chêneau brace on load symmetry during standing and those on symmetry of gait (R>0.5, P<0.05). CONCLUSION AND CLINICAL REHABILITATION IMPACT: Our results show slight changes in terms of posture when wearing Chêneau brace according with the severity of pathology and significantly affecting gait parameters. For these reasons, use of postural balance evaluation should be objectively used to verify the efficacy of Cheneau brace on body functioning of adolescents with idiopathic scoliosis.

Role, indications, and controversies of antidepressant therapy in chronic stroke patients.

Antidepressants are a heterogeneous class of drugs that have been developed for the treatment of mood disorders. In the past several years, they have been used in poststroke survivors to treat poststroke depression, central poststroke pain, and poststroke fatigue and as an adjuvant for functional recovery and cognitive function. However, there are still some relevant points to clarify regarding the real role of antdidepressants in stroke patients and further researches are needed to deeply explore their effects on rehabilitation results.

Adaptive latitudinal cline of photoperiodic diapause induction in the parasitoid Nasonia vitripennis in Europe.

Living in seasonally changing environments requires adaptation to seasonal cycles. Many insects use the change in day length as a reliable cue for upcoming winter and respond to shortened photoperiod through diapause. In this study, we report the clinal variation in photoperiodic diapause induction in populations of the parasitoid wasp Nasonia vitripennis collected along a latitudinal gradient in Europe. In this species, diapause occurs in the larval stage and is maternally induced. Adult Nasonia females were exposed to different photoperiodic cycles and lifetime production of diapausing offspring was scored. Females switched to the production of diapausing offspring after exposure to a threshold number of photoperiodic cycles. A latitudinal cline was found in the proportion of diapausing offspring, the switch point for diapause induction measured as the maternal age at which the female starts to produce diapausing larvae, and the critical photoperiod for diapause induction. Populations at northern latitudes show an earlier switch point, higher proportions of diapausing individuals and longer critical photoperiods. Since the photoperiodic response was measured under the same laboratory conditions, the observed differences between populations most likely reflect genetic differences in sensitivity to photoperiodic cues, resulting from local adaptation to environmental cycles. The observed variability in diapause response combined with the availability of genomic tools for N. vitripennis represent a good opportunity to further investigate the genetic basis of this adaptive trait.