Filipa Sousa

Effects of resistance and aerobic exercise on physical function, bone mineral density, OPG and RANKL in older women.

This study compared the effects of a resistance training protocol and a moderate-impact aerobic training protocol on bone mineral density (BMD), physical ability, serum osteoprotegerin (OPG), and receptor activator of nuclear factor kappa B ligand (RANKL) levels. Seventy-one older women were randomly assigned to resistance exercise (RE), aerobic exercise (AE) or a control group (CON). Both interventions were conducted 3 times per week for 8 months. Outcome measures included proximal femur BMD, muscle strength, balance, body composition, serum OPG, and RANKL levels. Potential confounding variables included dietary intake, accelerometer-based physical activity (PA), and molecularly defined lactase nonpersistence. After 8 months, only RE group exhibited increases in BMD at the trochanter (2.9%) and total hip (1.5%), and improved body composition. Both RE and AE groups improved balance. No significant changes were observed in OPG and RANKL levels, and OPG/RANKL ratio. Lactase nonpersistence was not associated with BMD changes. No group differences were observed in baseline values or change in dietary intakes and daily PA. Data suggest that 8 months of RE may be more effective than AE for inducing favourable changes in BMD and muscle strength, whilst both interventions demonstrate to protect against the functional balance control that is strongly related to fall risk.

Metabolic syndrome and risk of cancer: Which link?

Metabolic syndrome (MS) is characterized by a group of metabolic disturbances which lead to an enhanced risk of cardiovascular diseases and type 2 diabetes mellitus. MS constitutes a preoccupant issue with elevated prevalence in the western countries and is often related with cancer development. Elucidating the mechanisms linking these two pathologies is, therefore, essential to identify potential therapeutic molecular targets for cancer treatment in MS patients. The main goals of this review are, to identify the relation between MS and cancer development, handling specifically each one of the main players on this process: insulin and IGF system, estrogen, pro-inflammatory cytokines and others; and, given that colorectal cancer is one of the most prevalent types of cancer in MS patients, we intend to particularly highlight the mechanisms that promote colorectal cancer development in MS individuals. Finally, we will also focus on the clinical implications of the presented mechanisms on cancer therapy and care.

Interlimb Coordination During the Stance Phase of Gait in Subjects With Stroke

OBJECTIVE To analyze the relation between contralesional and ipsilesional limbs in subjects with stroke during step-to-step transition of walking. DESIGN Observational, transversal, analytical study with a convenience sample. SETTING Physical medicine and rehabilitation clinic. PARTICIPANTS Subjects (n=16) with poststroke hemiparesis with the ability to walk independently and healthy controls (n=22). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Bilateral lower limbs electromyographic activity of the soleus (SOL), gastrocnemius medialis, tibialis anterior, biceps femoris, rectus femoris, and vastus medialis (VM) muscles and the ground reaction force were analyzed during double-support and terminal stance phases of gait. RESULTS The propulsive impulse of the contralesional trailing limb was negatively correlated with the braking impulse of the leading limb during double support (r=-.639, P=.01). A moderate functional relation was observed between thigh muscles (r=-.529, P=.035), and a strong and moderate dysfunctional relation was found between the plantar flexors of the ipsilesional limb and the vastus medialis of the contralesional limb, respectively (SOL-VM, r=-.80, P<.001; gastrocnemius medialis-VM, r=-.655, P=.002). Also, a functional moderate negative correlation was found between the SOL and rectus femoris muscles of the ipsilesional limb during terminal stance and between the SOL (r=-.506, P=.046) and VM (r=-.518, P=.04) muscles of the contralesional limb during loading response, respectively. The trailing limb relative impulse contribution of the contralesional limb was lower than the ipsilesional limb of subjects with stroke (P=.02) and lower than the relative impulse contribution of the healthy limb (P=.008) during double support. CONCLUSIONS The findings obtained suggest that the lower performance of the contralesional limb in forward propulsion during gait is related not only to contralateral supraspinal damage but also to a dysfunctional influence of the ipsilesional limb.

Ankle dynamic in stroke patients: Agonist vs. antagonist muscle relations

Introduction: Atypical ankle patterns of muscle activity during gait are commonly reported in patients with stroke. These findings can be due to changes between tibialis anterior (TA) and soleus (SOL) coactivation mechanisms. Objective: To compare the electromyographic activity (EMGa) of SOL and TA muscles and antagonist coactivation (C) level in the contralateral (CONTRA) and ipsilateral (IPSI) limbs to the side of the stroke lesion during the stance phase of the gait cycle. Methods: Twelve subjects with a stroke episode participated in this study. The electromyographic signal of TA and SOL and ground reaction forces were acquired while subjects walked at their self-selected speed. Values of ground reaction forces were used to divide the stance phase of gait into initial contact, midstance, and terminal stance. In each sub-phase, the magnitude of TA and SOL was calculated as well as the level of the antagonist C. Results: Although no statistical differences were found, mean values of SOL EMGa were lower in the IPSI limb in all stance phases in relation to the CONTRA limb, and the opposite was observed in the TA EMGa. Moreover, higher mean levels of antagonist C were only found during the initial contact sub-phase in the CONTRA limb and in the other sub-phases in the IPSI limb. Besides, statistical differences were observed only during midstance. Conclusion: In stroke subjects, the antagonist C level during midstance of gait may reflect the dysfunction of the neuronal system over the IPSI limb.

Activation timing of soleus and tibialis anterior muscles during sit-to-stand and stand-to-sit in post-stroke vs. healthy subjects

Introduction. Sit-to-stand (SitTS) and stand-to-sit (StandTS) are very important functional tasks that become compromised in stroke patients. As in other voluntary movements, they require an adequate postural control (PC) involving the generation of anticipatory postural adjustments (APAs). In order to give clues for more efficient and directed rehabilitation programs, a deeper knowledge about APAs during challenging and daily life movements is essential. Purpose. To analyze the activation timing of tibialis anterior (TA) and soleus (SOL) muscles during SitTS and StandTS in healthy subjects and in post-stroke patients. Methods. Two groups participated in this study: one composed of ten healthy subjects and the other by ten subjects with a history of stroke and increased H-reflex. Electromyographic activity (EMGa) of SOL and TA was analyzed during SitTS and StandTS in the ipsilateral (IPSI) and the contralateral (CONTRA) limb to the side lesion in stroke subjects, and in one limb in healthy subjects. A force plate was used to identify the movement onset. Results. In both sequences, in the stroke group SOL activation timing occurred prior to movement onset, contrary to the pattern observed in the healthy subjects. Statistically significant differences were found in SOL activation timings between each lower limb of the stroke and healthy groups, but no significant differences were found between the IPSI and the CONTRA limb. The TA activation timing seems to be delayed in the CONTRA limb when compared to the healthy subjects and showed a better organization of TA timing activation in StandTS when compared to SitTS. Conclusion. Compared to healthy subjects, APAs seem to be altered in both limbs of the post-stroke subjects, with the SOL activation timing being anticipated in both SitTS and StandTS.

Accuracy and Repeatability of the Gait Analysis by the WalkinSense System

WalkinSense is a new device designed to monitor walking. The aim of this study was to measure the accuracy and repeatability of the gait analysis performed by the WalkinSense system. Descriptions of values recorded by WalkinSense depicting typical gait in adults are also presented. A bench experiment using the Trublu calibration device was conducted to statically test the WalkinSense. Following this, a dynamic test was carried out overlapping the WalkinSense and the Pedar insoles in 40 healthy participants during walking. Pressure peak, pressure peak time, pressure-time integral, and mean pressure at eight-foot regions were calculated. In the bench experiments, the repeatability (i) among the WalkinSense sensors (within), (ii) between two WalkinSense devices, and (iii) between the WalkinSense and the Trublu devices was excellent. In the dynamic tests, the repeatability of the WalkinSense (i) between stances in the same trial (within-trial) and (ii) between trials was also excellent (ICC > 0.90). When the eight-foot regions were analyzed separately, the within-trial and between-trials repeatability was good-to-excellent in 88% (ICC > 0.80) of the data and fair in 11%. In short, the data suggest that the WalkinSense has good-to-excellent levels of accuracy and repeatability for plantar pressure variables.

Soleus activity in post-stroke subjects: Movement sequence from standing to sitting

Introduction. The beginning of the movement sequence from standing to sitting requires the modulation of plantar flexors activity, including the soleus muscle (SOL), to allow the forward translation of the tibia in relation to the foot, preserving its antigravity function. Purpose. To analyze the SOL activity during the initial phase of standing to sitting in stroke subjects. Methods. Two groups of ten subjects each participated in this study, one composed of healthy subjects and the other with subjects with a history of stroke. Electromyographic activity (EMGa) of SOL was analyzed in the ipsilateral (IPSI) and contralateral (CONTRA) limb to side lesion in stroke subjects, and in one limb in healthy subjects during the initial phase of standing to sitting. A force plate was used to identify the movement sequence phase. Results. The mean values of SOL EMGa were higher in healthy subjects than the ones obtained in the IPSI and CONTRA limb in stroke subjects. Significant differences were only observed between the IPSI and healthy limb (p = 0.035). Conclusion. When compared to the healthy subjects, stroke subjects showed a decreased SOL EMGa in the IPSI limb, which suggests that therapeutic decisions must consider the need to promote a better postural control also in the IPSI limb.

Ankle antagonist coactivation in the double-support phase of walking: stroke vs. healthy subjects

Abstract Introduction: Lesions in ipsilateral systems related to postural control in the ipsilesional side may justify the lower performance of stroke subjects during walking. Purpose. To analyze bilateral ankle antagonist coactivation during double support in stroke subjects. Methods: Sixteen (8 females; 8 males) subjects with a first isquemic stroke and 22 controls (12 females; 10 males) participated in this study. The double-support phase was assessed through ground reaction forces and the electromyography of ankle muscles was assessed in both limbs. Results: The ipsilesional limb presented statistically significant differences from the control when assuming specific roles during double support. The tibialis anterior and soleus pair was the one in which this atypical behavior was more pronounced. Conclusion: The ipsilesional limb presents a dysfunctional behavior when a higher postural control activity was demanded.

Dissecting the signaling pathways associated with the oncogenic activity of MLK3 P252H mutation

BackgroundMLK3 gene mutations were described to occur in about 20% of microsatellite unstable gastrointestinal cancers and to harbor oncogenic activity. In particular, mutation P252H, located in the kinase domain, was found to have a strong transforming potential, and to promote the growth of highly invasive tumors when subcutaneously injected in nude mice. Nevertheless, the molecular mechanism underlying the oncogenic activity of P252H mutant remained elusive.MethodsIn this work, we performed Illumina Whole Genome arrays on three biological replicas of human HEK293 cells stably transfected with the wild-type MLK3, the P252H mutation and with the empty vector (Mock) in order to identify the putative signaling pathways associated with P252H mutation.ResultsOur microarray results showed that mutant MLK3 deregulates several important colorectal cancer- associated signaling pathways such as WNT, MAPK, NOTCH, TGF-beta and p53, helping to narrow down the number of potential MLK3 targets responsible for its oncogenic effects. A more detailed analysis of the alterations affecting the WNT signaling pathway revealed a down-regulation of molecules involved in the canonical pathway, such as DVL2, LEF1, CCND1 and c-Myc, and an up-regulation of DKK, a well-known negative regulator of canonical WNT signaling, in MLK3 mutant cells. Additionally, FZD6 and FZD10 genes, known to act as negative regulators of the canonical WNT signaling cascade and as positive regulators of the planar cell polarity (PCP) pathway, a non-canonic WNT pathway, were found to be up-regulated in P252H cells.ConclusionThe results provide an overall view of the expression profile associated with mutant MLK3, and they support the functional role of mutant MLK3 by showing a deregulation of several signaling pathways known to play important roles in the development and progression of colorectal cancer. The results also suggest that mutant MLK3 may be a novel modulator of WNT signaling, and pinpoint the activation of PCP pathway as a possible mechanism underlying the invasive potential of MLK3 mutant cells.

Influence of prolonged wearing of unstable shoes on upright standing postural control

OBJECTIVE To study the influence of prolonged wearing of unstable shoes on standing postural control in prolonged standing workers. METHODS The participants were divided into two groups: one wore unstable shoes while the other wore conventional shoes for 8weeks. Stabilometry parameters related to centre of pressure (CoP), rambling (RM) and trembling (TR) as well as the total agonist/antagonist muscle activity, antagonist co-activation and reciprocal activation were evaluated during upright standing, before and after the 8weeks period. In both moments, the subjects were evaluated wearing the unstable shoes and in barefoot. RESULTS The unstable shoe condition presented increased CoP displacement related variables and decreased co-activation command compared to barefoot before and after the intervention. The prolonged wearing of unstable shoes led to: (1) reduction of medial-lateral CoP root mean square and area; (2) decreased anteroposterior RM displacement; (3) increased anteroposterior RM mean velocity and mediolateral RM displacement; (4) decreased anteroposterior TR RMS; and (5) increased thigh antagonist co-activation in the unstable shoe condition. CONCLUSION The unstable shoe condition is associated to a higher destabilising effect that leads to a selection of more efficient and accurate postural commands compared to barefoot. Prolonged wearing of unstable shoes provides increased effectiveness and performance of the postural control system, while wearing of unstable shoes in upright standing, that are reflected by changes in CoP related variables and by a reorganisation of postural control commands.