Roberto Gatti

Intra-arterial transplantation of HLA-matched donor mesoangioblasts in Duchenne muscular dystrophy

Intra‐arterial transplantation of mesoangioblasts proved safe and partially efficacious in preclinical models of muscular dystrophy. We now report the first‐in‐human, exploratory, non‐randomized open‐label phase I–IIa clinical trial of intra‐arterial HLA‐matched donor cell transplantation in 5 Duchenne patients. We administered escalating doses of donor‐derived mesoangioblasts in limb arteries under immunosuppressive therapy (tacrolimus). Four consecutive infusions were performed at 2‐month intervals, preceded and followed by clinical, laboratory, and muscular MRI analyses. Two months after the last infusion, a muscle biopsy was performed. Safety was the primary endpoint. The study was relatively safe: One patient developed a thalamic stroke with no clinical consequences and whose correlation with mesoangioblast infusion remained unclear. MRI documented the progression of the disease in 4/5 patients. Functional measures were transiently stabilized in 2/3 ambulant patients, but no functional improvements were observed. Low level of donor DNA was detected in muscle biopsies of 4/5 patients and donor‐derived dystrophin in 1. Intra‐arterial transplantation of donor mesoangioblasts in human proved to be feasible and relatively safe. Future implementation of the protocol, together with a younger age of patients, will be needed to approach efficacy.

Rehabilitation that incorporates virtual reality is more effective than standard rehabilitation for improving walking speed, balance and mobility after stroke: a systematic review

QUESTION In people after stroke, does virtual reality based rehabilitation (VRBR) improve walking speed, balance and mobility more than the same duration of standard rehabilitation? In people after stroke, does adding extra VRBR to standard rehabilitation improve the effects on gait, balance and mobility? DESIGN Systematic review with meta-analysis of randomised trials. PARTICIPANTS Adults with a clinical diagnosis of stroke. INTERVENTION Eligible trials had to include one these comparisons: VRBR replacing some or all of standard rehabilitation or VRBR used as extra rehabilitation time added to a standard rehabilitation regimen. OUTCOME MEASURES Walking speed, balance, mobility and adverse events. RESULTS In total, 15 trials involving 341 participants were included. When VRBR replaced some or all of the standard rehabilitation, there were statistically significant benefits in walking speed (MD 0.15 m/s, 95% CI 0.10 to 0.19), balance (MD 2.1 points on the Berg Balance Scale, 95% CI 1.8 to 2.5) and mobility (MD 2.3 seconds on the Timed Up and Go test, 95% CI 1.2 to 3.4). When VRBR was added to standard rehabilitation, mobility showed a significant benefit (0.7 seconds on the Timed Up and Go test, 95% CI 0.4 to 1.1), but insufficient evidence was found to comment about walking speed (one trial) and balance (high heterogeneity). CONCLUSION Substituting some or all of a standard rehabilitation regimen with VRBR elicits greater benefits in walking speed, balance and mobility in people with stroke. Although the benefits are small, the extra cost of applying virtual reality to standard rehabilitation is also small, especially when spread over many patients in a clinic. Adding extra VRBR time to standard rehabilitation also has some benefits; further research is needed to determine if these benefits are clinically worthwhile.

Motor Learning in Healthy Humans Is Associated to Gray Matter Changes: A Tensor-Based Morphometry Study

We used tensor-based morphometry (TBM) to: 1) map gray matter (GM) volume changes associated with motor learning in young healthy individuals; 2) evaluate if GM changes persist three months after cessation of motor training; and 3) assess whether the use of different schemes of motor training during the learning phase could lead to volume modifications of specific GM structures. From 31 healthy subjects, motor functional assessment and brain 3D T1-weighted sequence were obtained: before motor training (time 0), at the end of training (two weeks) (time 2), and three months later (time 3). Fifteen subjects (group A) were trained with goal-directed motor sequences, and 16 (group B) with non purposeful motor actions of the right hand. At time 1 vs. time 0, the whole sample of subjects had GM volume increase in regions of the temporo-occipital lobes, inferior parietal lobule (IPL) and middle frontal gyrus, while at time 2 vs. time 1, an increased GM volume in the middle temporal gyrus was seen. At time 1 vs. time 0, compared to group B, group A had a GM volume increase of the hippocampi, while the opposite comparison showed greater GM volume increase in the IPL and insula in group B vs. group A. Motor learning results in structural GM changes of different brain areas which are part of specific neuronal networks and tend to persist after training is stopped. The scheme applied during the learning phase influences the pattern of such structural changes.

Intra-rater reliability of an experienced physiotherapist in locating myofascial trigger points in upper trapezius muscle

Abstract Objectives: Myofascial trigger points (MTrPs) are considered the principal clinical feature of myofascial pain syndrome (MPS). An MTrP consists of spot tenderness within a taut band of muscle fibers and its stimulation can produce both local and referred pain. The clinical diagnosis of MPS depends on correct history taking and a physical examination aimed at identifying the presence of MTrP. The purpose of this study was to investigate the intra-rater reliability of a palpation protocol used for locating an MTrP in the upper trapezius muscle. Methods: Twenty-four subjects with MTrP in the upper trapezius muscle were examined by an experienced physiotherapist. During each of eight experimental sessions, subjects were examined twice in randomized order using a palpation protocol. An anatomical landmark system was defined and the MTrP location established using X and Y values. Results: The intraclass correlation coefficient ICC(1,1) values were 0·62 (95% CI: 0·30–0·81) for X and 0·81 (95% CI: 0·61–0·91) for Y. The Bland–Altman plots for X and Y showed a mean of difference of 0·04 and −0·2 mm, respectively. Limits of agreement for X ranged from −26·3 to 26·2 mm and for Y from −27 to 26·4 mm. Discussion: The ICC(1,1) for the observed values revealed a moderate to high correlation and the Bland–Altman analysis showed means of difference very close to zero with narrow limits of agreement. An experienced physiotherapist can reliably identify MTrP locations in upper trapezius muscle using a palpation protocol.

Brain structural and functional connectivity in Parkinson's disease with freezing of gait

To use a multimodal approach to assess brain structural pathways and resting state (RS) functional connectivity abnormalities in patients with Parkinsons disease and freezing of gait (PD‐FoG).

Aerobic and resistance training effects compared to aerobic training alone in obese type 2 diabetic patients on diet treatment

AIMS The study was designed to compare a combined aerobic and resistance training (ART) with an aerobic training (AT) over hemodynamic, glucose metabolism and endothelial factors, adipokines and pro-inflammatory marker release in a population of obese type 2 diabetic patients. METHODS Forty-seven patients were randomly assigned to aerobic (27 patients) or aerobic plus resistance (20 patients) exercise trainings, on the top of a diet regime. Anthropometric, metabolic, hormonal and inflammatory variables were measured at hospitalization and discharge. RESULTS Both exercise programs equally improved body weight and fructosamine levels however ART only partially decreased HOMA index compared with AT (ART: -25% vs AT: -54%, p<0.01). Mean blood pressure (AT: -3.6 mmHg vs ART: +0.6 mmHg, p<0.05) and endothelin-1 (ET-1) incremental areas during walking test (AT: -11% vs ART: +30%, p<0.001) decreased after AT while increased after ART. Adiponectin levels increased by 54% after AT while decreased by 13% after ART (p<0.0001) and matrix metalloproteinase-2 (MMP-2), tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractan protein-1 (MCP-1) levels significantly decreased in AT while increased in ART group. CONCLUSIONS Compared with AT, ART similarly enhanced body weight loss but exerted less positive effects on insulin sensitivity and endothelial factors, adipokines and pro-inflammatory marker release.

Efficacy of Trunk Balance Exercises for Individuals With Chronic Low Back Pain: A Randomized Clinical Trial

STUDY DESIGN Randomized clinical trial. OBJECTIVES To determine the efficacy of trunk balance exercises for individuals with chronic low back pain. BACKGROUND The majority of exercises focusing on restoring lumbopelvic stability propose targeting the feedforward control of the lumbopelvic region. Less attention has been paid to feedback control during balance adjustments. METHODS Seventy-nine patients were randomly allocated to 2 different groups. The experimental group performed trunk balance exercises in addition to standard trunk flexibility exercises. The control group performed strengthening exercises in addition to the same standard trunk flexibility exercises. The primary outcome measures were pain intensity (visual analogue scale), disability (Roland-Morris Questionnaire), and quality of life (12-Item Short-Form Health Survey). Secondary outcomes were painful positions, use of analgesic drugs, and referred pain. Analysis of variance and relative risk were used to analyze the data for the primary and secondary outcome measures, respectively. The number of participants reaching the minimal clinically important difference in the 2 groups for each outcome measure was compared using relative risk. RESULTS A significant difference in scores on the Roland-Morris Questionnaire (P = .011) and the physical component of the 12-Item Short-Form Health Survey (P = .048), and in the number of participants reaching the minimal clinically important difference for the Roland-Morris Questionnaire (relative risk, 1.79; 95% confidence interval [CI]: 1.05, 3.04) and the secondary outcome of painful positions (relative risk, 1.37; 95% CI: 1.03, 1.83) were found in favor of the experimental treatment. CONCLUSIONS Trunk balance exercises combined with flexibility exercises were found to be more effective than a combination of strength and flexibility exercises in reducing disability and improving the physical component of quality of life in patients with chronic low back pain.

Flexible electrogoniometers: kinesiological advantages with respect to potentiometric goniometers

Unlike conventional potentiometric goniometers, flexible electrogoniometers do not suffer from any alignment problems with respect to the joint axis. We hypothesized that flexible goniometers provide more valid measurements in that they avoid some biomechanical pitfalls. With both devices simultaneously we measured the movements of dorsal flexion of the ankle and flexion of the knee in three healthy subjects. In the various subjects, this comparison showed that the flexible goniometers signalled ankle excursion greater by 19-40% with the foot remaining in neutral position or being simultaneously pronated, and lower by 10-21% with the foot being simultaneously supinated. At the knee the flexible goniometers signalled a flexion greater by 24-32%, with respect to potentiometric goniometers. Biomechanical considerations support the validity of records taken with flexible goniometers, potentiometric measures being biased by (a) multijoint, multiplane motions underlying foot dorsal flexion, and (b) multiaxis motion underlying knee flexion RELEVANCE: In measurements of angles between adjacent body segments, flexible goniometers should be preferred to potentiometric goniometers despite their higher cost. Flexible goniometers not only are more practical: more importantly, they provide a valid measure of relative orientations in one plane, regardless of the number and different concurrent motions of the underlying joints.

Long tree-ring chronologies provide evidence of recent tree growth decrease in a Central African tropical forest.

It is still unclear whether the exponential rise of atmospheric CO2 concentration has produced a fertilization effect on tropical forests, thus incrementing their growth rate, in the last two centuries. As many factors affect tree growth patterns, short -term studies might be influenced by the confounding effect of several interacting environmental variables on plant growth. Long-term analyses of tree growth can elucidate long-term trends of plant growth response to dominant drivers. The study of annual rings, applied to long tree-ring chronologies in tropical forest trees enables such analysis. Long-term tree-ring chronologies of three widespread African species were measured in Central Africa to analyze the growth of trees over the last two centuries. Growth trends were correlated to changes in global atmospheric CO2 concentration and local variations in the main climatic drivers, temperature and rainfall. Our results provided no evidence for a fertilization effect of CO2 on tree growth. On the contrary, an overall growth decline was observed for all three species in the last century, which appears to be significantly correlated to the increase in local temperature. These findings provide additional support to the global observations of a slowing down of C sequestration in the trunks of forest trees in recent decades. Data indicate that the CO2 increase alone has not been sufficient to obtain a tree growth increase in tropical trees. The effect of other changing environmental factors, like temperature, may have overridden the fertilization effect of CO2.

Influence of body segment position during in-phase and antiphase hand and foot movements: A kinematic and functional MRI study

Behavioral studies have provided important insights into the mechanisms governing interlimb coordination. In this study, we combined kinematic and functional magnetic resonance imaging (fMRI) analysis to investigate the brain cortical and subcortical areas involved in interlimb coordination and the influence of direction of movement and of body segment position on the activity of those areas. Fifteen right‐handed healthy subjects were studied while performing cyclic in‐phase and antiphase hand and foot movements with the dominant, right limbs, with the upper limb positioned either prone or supine, and in front or behind with respect to the trunk. When contrasting antiphase to in‐phase movements, fMRI analysis demonstrated an increased recruitment of a widespread sensorimotor network (including regions in the frontal and parietal lobes, bilaterally, the cingulated motor area, the thalami, the visual cortex, and the cerebellum) considered to function in motor, sensory, and multimodal integration processing. When contrasting the anterior to the posterior position of the upper limb with respect to the trunk, we found different recruitment patterns in the frontal and parietal regions as well as the preferential recruitment of the basal ganglia, the insula, and the cerebellum during the first condition and of regions located in the temporal lobes during the second one. Different brain areas are engaged at a different extent during interlimb coordination. In addition to the relative difficulty of the movement, the different cognitive and sensorial loads needed to control and perform the motor act might be responsible for these findings. Hum Brain Mapp, 2007.