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Laser microdissection (LMD) is an accurate and fast method to procure pure populations of cells from complex, heterogeneous tissues under direct microscopic visualization. It can be applied to a wide [...]

Capacitive and resistive electric transfer (CRET), an endogenous diathermy treatment, has been demonstrated to reduce pain and improve quality of life in numerous orthopedic degenerative and inflammatory problems but not in knee osteoarthritis (KOA). The aim of this prospective randomized controlled trial was to evaluate whether a 2-week program of CRET can reduce pain, stiffness and functional limitations in KOA compared with a sham treatment. Patients with KOA were randomly assigned to a study group (n= 31) or a control one (n= 22). The study group underwent six intermittent CRET applications, whereas the controls underwent a sham protocol without application of energy. The outcome measures were the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) (primary outcome) and the visual analogue scale (VAS) for pain and Medical Research Council Scale (secondary outcomes). All patients were evaluated before treatment (T0), at the end of treatment (T1), and at 1 (T2) and 3 months after treatment (T3). Results showed that CRET significantly improved strength, physical function and pain in patients with KOA. In the study group a reduction in WOMAC and VAS scores was observed at T1, T2, and T3compared with T0. No significant changes of WOMAC and VAS scores were observed in the control group across all time points. Considering the small number of sessions, low cost and long-term benefits, CRET might be a useful therapeutic option for the conservative management of KOA to reduce pain, stiffness and functional limitation.

Mobile health apps are growing constantly in number and popularity. Some mobile apps are used for clinical assessment, and consequently need to be verified and validated appropriately, along with the mobile platform, to ensure their safe and effective operation. We review the current literature on available smartphone goniometric apps validated for joint angle measurement and their main psychometric characteristics. A literature search of Medline and Scopus databases was performed to select papers on smartphone commercial apps validated for joint angle measurement and relevant to Physical Medicine and Rehabilitation. A platform search verified whether the selected apps were still available for download. The literature search identified 126 papers in Medline and 113 in Scopus, 49 of which were selected. They dealt with the validation of 23 apps, eight of which were no longer available and therefore excluded from the review. Psychometric characteristics of the selected apps were robust, but heterogeneity of the studies did not enable comparisons between apps to identify the most valid one. The increase in the number of apps and validation studies highlights the growing interest in this new approach for measuring body angles. Given the precarious commercial availability of some apps, when research is the goal, it is advisable to select apps with the longest durability. A need continues to exist for validation studies on available apps focused on goniometric measurement in gait or during performance of therapeutic exercises in neurological and orthopedic disorders.

Nonenzymatic glycation has been implicated in the pathogenesis of the dysregulated tissue remodeling that characterizes diabetic glomerulopathy, via the formation of advanced glycation end products (AGEs) and their binding to [...]

Stroke is the leading cause of permanent disability in developed countries; its effects may include sensory, motor, and cognitive impairment as well as a reduced ability to perform self-care and participate in social and community activities. A number of studies have shown that the use of robotic systems in upper limb motor rehabilitation programs provides safe and intensive treatment to patients with motor impairments because of a neurological injury. Furthermore, robot-aided therapy was shown to be well accepted and tolerated by all patients; however, it is not known whether a specific robot-aided rehabilitation can induce beneficial cortical plasticity in stroke patients. Here, we present a procedure to study neural underpinning of robot-aided upper limb rehabilitation in stroke patients. Neurophysiological recordings use the following: (a) 10–20 system electroencephalographic (EEG) electrode montage; (b) bipolar vertical and horizontal electrooculographies; and (c) bipolar electromyography from the operating upper limb. Behavior monitoring includes the following: (a) clinical data and (b) kinematic and dynamic of the operant upper limb movements. Experimental conditions include the following: (a) resting state eyes closed and eyes open, and (b) robotic rehabilitation task (maximum 80 s each block to reach 4-min EEG data; interblock pause of 1 min). The data collection is performed before and after a program of 30 daily rehabilitation sessions. EEG markers include the following: (a) EEG power density in the eyes-closed condition; (b) reactivity of EEG power density to eyes opening; and (c) reactivity of EEG power density to robotic rehabilitation task. The above procedure was tested on a subacute patient (29 poststroke days) and on a chronic patient (21 poststroke months). After the rehabilitation program, we observed (a) improved clinical condition; (b) improved performance during the robotic task; (c) reduced delta rhythms (1–4 Hz) and increased alpha rhythms (8–12 Hz) during the resting state eyes-closed condition; (d) increased alpha desynchronization to eyes opening; and (e) decreased alpha desynchronization during the robotic rehabilitation task. We conclude that the present procedure is suitable for evaluation of the neural underpinning of robot-aided upper limb rehabilitation.

New treatments based on peripheral stimulation of the sensory–motor system have been inspiring new rehabilitation approaches in Parkinson’s disease (PD), especially to reduce gait impairment, levodopa washout effects, and the incidence of falls. The aim of this study was to evaluate the change in gait and the clinical status of PD patients after six sessions of a treatment based on automated mechanical peripheral stimulation (AMPS). Eighteen patients with PD and 15 age-matched healthy individuals (control group) participated in this study. A dedicated medical device delivered the AMPS. PD patients were treated with AMPS six times once every 4 days. All PD patients were treated in the off-levodopa phase and were evaluated with gait analysis before and after the first intervention (acute phase), after the sixth intervention, 48 h after the sixth intervention, and 10 days after the end of the treatment. To compare the differences among the AMPS interventions (pre, 6 AMPS, and 10 days) in terms of clinical scales, a t-test was used (α≤0.05). In addition, to compare the differences among the AMPS interventions (pre, post, 6 AMPS, 48 h and 10 days), the gait spatiotemporal parameters were analyzed using the Friedman test and the Bonferroni post-hoc test (α≤0.05). Also, for comparisons between the PD group and the control group, the gait spatiotemporal parameters were analyzed using the Mann–Whitney test and the Bonferroni post-hoc test (α≤0.05). The results of the study indicate that the AMPS treatment has a positive effect on bradykinesia because it improves walking velocity, has a positive effect on the step and stride length, and has a positive effect on walking stability, measured by the increase in stride length. These results are consistent with the improvements measured with clinical scales. These findings indicate that AMPS treatment seems to generate a more stable walking pattern in PD patients, reducing the well-known gait impairment that is typical of PD; regular repetition every 4 days of AMPS treatment appears to be able to improve gait parameters, to restore rhythmicity, and to reduce the risk of falls, with benefits maintained up to 10 days after the last treatment. The trial was registered online at ClinicalTrials.gov (number identifier: NCT0181528).

In the last few years, not many studies on the use of robot-assisted therapy to recover hand function in acute stroke patients have been carried out. This randomized-controlled observer trial is aimed at evaluating the effects of intensive robot-assisted hand therapy compared with intensive occupational therapy in the early recovery phases after stroke with a 3-month follow-up. Twenty acute stroke patients at their first-ever stroke were enrolled and randomized into two groups. The experimental treatment was performed using the Amadeo Robotic System. Control treatment, instead, was carried out using occupational therapy executed by a trained physiotherapist. All participants received 20 sessions of treatment for 4 consecutive weeks (5 daysweek). The following clinical scales, Fugl-Meyer Scale (FM), Medical Research Council Scale for Muscle Strength (hand flexor and extensor muscles) (MRC), Motricity Index (MI) and modified Ashworth Scale for wrist and hand muscles (MAS), were performed at baseline (T0), after 20 sessions (end of treatment) (T1) and at the 3-month follow-up (T2). The Barthel Index was assessed only at T0 and T1. Evidence of a significant improvement was shown by the Friedman test for the FM experimental group (EG): P=0.0039, control group (CG): P<0.0001, Box and Block Test (EG: P=0.0185, CG: P=0.0086), MI (EG: P<0.0001, CG: P=0.0303) and MRC (EG: P<0.0001, CG: P=0.001) scales. These results provide further support to the generalized therapeutic impact of intensive robot-assisted treatment on hand recovery functions in individuals with acute stroke. The robotic rehabilitation treatment may contribute toward the recovery of hand motor function in acute stroke patients. The positive results obtained through the safe and reliable robotic rehabilitation treatment reinforce the recommendation to extend it to a larger clinical practice.

The aim of this study was to determine short-term and long-term changes in motor function in patients with chronic hemiparesis who underwent robot training and to evaluate its long-term benefit after 6 months. This was a longitudinal study with a 6-month follow-up. The 15 patients included in this study underwent the Fugl-Meyer test, the Ashworth Scale test, the Frenchay Arm test, and the Box and Block test according to the following schedule: immediately before (T1, T3) and after each treatment (T2, T4), and 6 months after T4 (T5). There were statistically significant improvements in Fugl-Meyer test between T1 and T2 and between T1 and T4; the score increased in the Ashworth Scale test for Shoulder between T1 and T3 and between T1 and T5; a statistically significant decrease was found between T1 and T2 and between T1 and T4, in the Box and Block test between T1 and T4, and also between T1 and T5. This original rehabilitation treatment may contribute toward increasing upper limb motor recovery in stable chronic stroke patients.

NG108-15 cells differentiate into neurons by 1 mM sodium butyrate (NaB) treatment. Differentiated cells resulted more resistant to staurosporine (STS) than proliferating cells. In particular, STS treatment decreased Bcl-2 and Bcl-xL content in mitochondria of proliferating cells, but not in mitochondria of differentiated cells. Bad was phosphorylated and down-regulated only in differentiated cells. Bax accumulated in the mitochondria of proliferating but not differentiated cells. Mitochondrial release of cytochrome c was observed in proliferating cells, whereas mitochondria of differentiated cells retained cytochrome c. Proliferating cells treated with STS accumulated Endo G and AIF in the nucleus. By contrast, differentiated cells did not show such nuclear accumulation. Treatment of differentiated cells with Insulin-like Growth Factor-1 (IGF-1) and STS resulted in a 17,1% increase of cell viability. The survival role of IGF-1 was demonstrated by treating differentiated cells with an anti-IGF-1 neutralizing antibody. Such treatment significantly increased STS-induced cell death. Electrophysiology studies showed that in STS-treated cells membrane potential oscillations were reduced in amplitude without giving rise to spontaneous action potentials (APs). However, the percentage of cells yielding overshooting APs returned to 100% after STS removal. It is concluded that neuronal differentiation of NG108-15 cells induces resistance to apoptotic cell death and that IGF-1 plays a central role in sustaining this mechanism.

Adaptation to hypoxia through activation of the hypoxia inducible factor-1 (HIF-1) is crucial for tumor cells survival. Here we describe the antitumoral effects of the new molecule CR 3294 on tumor cells in the presence of hypoxia. Treatment of the breast carcinoma cell line MDA-MB-231 with CR 3294 in 1% O2 resulted in an in vivo and in vitro inhibition of tumor growth. CR 3294 induced accumulation of autophagosomes in hypoxic MDA-MB-231 cells as assessed by both transmission electron microscopy (TEM) and the autophagic marker LC3-II. TEM analysis revealed the presence of invaginations of the cytoplasm into the nucleus. Autophagosomes were present in such invaginations. Moreover, CR 3294 inhibited both the DNA binding of HIF-1α and VEGF mRNA synthesis. Immunoprecipitation and immunofluorescence studies showed an interaction between LC3 and HIF-1α. We next detailed the effect of inhibitors and activators of autophagy on both HIF-1α and LC3. In particular, 3 methyladenine (3MA) and wortmannin, two macroautophagic inhibitors, prevented both the decrease of HIF-1α protein levels and LC3 processing in cells treated with CR 3294. Bafilomycin and leupeptin, inhibitors of lysosomes, prevented HIF-1α decrease without affecting LC3 processing. By contrast, treating hypoxic MDA-MB-231 cells with trifluoperazine (TFP) or serum withdrawal (SW), two activators of autophagy, diminished HIF-1α levels and stimulated LC3 processing. These results indicate that activation of the autophagic pathway in hypoxic cells by the new molecule CR 3294, as well as by TFP or SW, can have potentially important implications for cancer treatment.

CXCR4 (fusin) is a chemokine receptor which is involved as a coreceptor in gp120 binding to the cell surface. In this study we provide evidence that binding of gp120 triggers CXCR4 recruitment to glycosphingolipid‐enriched microdomains. Scanning confocal microscopy showed a nearly complete localization of CXCR4 within GM3‐enriched plasma membrane domains of SupT1 cells and coimmunoprecipitation experiments revealed that CXCR4 was immunoprecipitated by IgG anti‐GM3 after gp120 pretreatment. These findings reveal that gp120 binding induces a strict association between CXCR4 and ganglioside GM3, supporting the view that GM3 and CXCR4 are components of a functional multimolecular complex critical for HIV‐1 entry.

This study aims to evaluate the change in gait spatiotemporal parameters in subjects with Parkinson’s disease (PD) before and after Automated Mechanical Peripheral Stimulation (AMPS) treatment. Thirty-five subjects with PD and 35 healthy age-matched subjects took part in this study. A dedicated medical device (Gondola) was used to administer the AMPS. All patients with PD were treated in off levodopa phase and their gait performances were evaluated by an inertial measurement system before and after the intervention. The one-way ANOVA for repeated measures was performed to assess the differences between pre- and post-AMPS and the one-way ANOVA to assess the differences between PD patients and the control group. Spearman’s correlations assessed the associations between patients with PD clinical status (H&Y) and the percentage of improvement of the gait variables after AMPS (α<0.05 for all tests). The PD group had an improvement of 14.85% in the stride length; 14.77% in the gait velocity; and 29.91% in the gait propulsion. The correlation results showed that the higher the H&Y classification, the higher the stride length percentage of improvement. The treatment based on AMPS intervention seems to induce a better performance in the gait pattern of PD patients, mainly in intermediate and advanced stages of the condition.