Prosthetic gait of unilateral lower-limb amputees with current and novel prostheses: A pilot study.

BACKGROUND: Novel lower-limb prostheses aim to improve the quality of locomotion of individuals with an amputation. This study evaluates the biomechanics of a novel bionic foot during walking. METHODS: Able-bodied individuals (n = 7) and individuals with a transfemoral (n = 6) or transtibial amputation (n = 6) were included. Able-bodied individuals conducted one experimental trial, whereas individuals with transtibial and transfemoral amputations conducted a familiarization (with current prosthesis) and two experimental trials using a passive and bionic prosthesis. Each trial consisted of 3 bouts of 2 min of treadmill walking at different speeds. Biomechanical data were gathered using a force platform and motion capture system and analysed using Statistical Parametric Mapping and (non)-parametric tests. FINDINGS: Conventional prosthetic feet alter gait patterns and induce locomotion difficulties. While walking at a normal speed with the passive prosthesis, transtibial amputees display reduced maximum heel forces, increased ankle and trunk angular velocities at midstance, and increased knee angle during stance and swing phases on their effected side (P ≤ 0.026). Improved lower-limb kinematics was demonstrated during slow and normal speed walking with the bionic prosthesis; however, dynamic trunk stability was negatively impacted during this condition. The bionic prosthesis did not benefit transfemoral amputees at any walking speed. INTERPRETATION: Transtibial amputees can better approximate typical movement patterns at slow and normal walking speeds using the novel bionic prosthesis; however the same benefit was not observed in transfemoral amputees.

EuGMS Task and Finish group on Fall-Risk-Increasing Drugs (FRIDs): Position on Knowledge Dissemination, Management, and Future Research.

Falls are a major public health concern in the older population, and certain medication classes are a significant risk factor for falls. However, knowledge is lacking among both physicians and older people, including caregivers, concerning the role of medication as a risk factor. In the present statement, the European Geriatric Medicine Society (EuGMS) Task and Finish group on fall-risk-increasing drugs (FRIDs), in collaboration with the EuGMS Special Interest group on Pharmacology and the European Union of Medical Specialists (UEMS) Geriatric Medicine Section, outlines its position regarding knowledge dissemination on medication-related falls in older people across Europe. The EuGMS Task and Finish group is developing educational materials to facilitate knowledge dissemination for healthcare professionals and older people. In addition, steps in primary prevention through judicious prescribing, deprescribing of FRIDs (withdrawal and dose reduction), and gaps in current research are outlined in this position paper.

EuGMS Task and Finish group on Fall-Risk-Increasing Drugs (FRIDs): Position on Knowledge Dissemination, Management, and Future Research.

Falls are a major public health concern in the older population, and certain medication classes are a significant risk factor for falls. However, knowledge is lacking among both physicians and older people, including caregivers, concerning the role of medication as a risk factor. In the present statement, the European Geriatric Medicine Society (EuGMS) Task and Finish group on fall-risk-increasing drugs (FRIDs), in collaboration with the EuGMS Special Interest group on Pharmacology and the European Union of Medical Specialists (UEMS) Geriatric Medicine Section, outlines its position regarding knowledge dissemination on medication-related falls in older people across Europe. The EuGMS Task and Finish group is developing educational materials to facilitate knowledge dissemination for healthcare professionals and older people. In addition, steps in primary prevention through judicious prescribing, deprescribing of FRIDs (withdrawal and dose reduction), and gaps in current research are outlined in this position paper.

Sigma-1 Receptor Agonism Promotes Mechanical Allodynia After Priming the Nociceptive System with Capsaicin.

Sigma-1 receptor antagonists promote antinociception in several models of pain, but the effects of sigma-1 agonists on nociception (particularly when the nociceptive system is primed) are not so well characterized; therefore we evaluated the effects of sigma-1 agonists on pain under different experimental conditions. The systemic administration of the selective sigma-1 agonists (+)-pentazocine and PRE-084, as well as the nonselective sigma-1 agonist carbetapentane (used clinically as an antitussive drug), did not alter sensitivity to mechanical stimulation under baseline conditions. However, they greatly promoted secondary mechanical allodynia after priming the nociceptive system with capsaicin. These effects of sigma-1 agonists were consistent in terms potency with the affinities of these drugs for sigma-1 receptors, were reversed by sigma-1 antagonists, and were not observed in sigma-1 knockout mice, indicating that they are sigma-1-mediated. Repeated systemic treatment with PRE-084 induced proallodynic effects even 24 h after treatment completion, but only after the nociceptive system was primed. However, neither the presence of this drug in the organism nor changes in sigma-1 receptor expression in areas involved in pain processing explains its long-term effects, suggesting that sustained sigma-1 agonism induces plastic changes in the nociceptive system that promote nociception.

Trends in lung cancer incidence by histologic subtype in the south of Spain, 1985-2012: a population-based study.

PURPOSE: To analyze and interpret age- and sex-specific incidence trends of lung cancer in Granada over the period 1985-2012 and to further analyze these trends by histologic subtype. METHODS: Incidence data were obtained from the population-based cancer registry located in Granada (Southern Spain). All cases with newly diagnosed primary lung cancer over the period 1985-2012 (n = 8658) and defined by International Classification of Diseases 10th Revision (codes C33-C34) were included. Joinpoint regression analysis of age-standardized incidence rates was used to estimate the annual percent change (APC) and 95% confidence intervals. Results are presented overall and by sex, age groups (0-34, 35-54, 55-64, 65-74, ≥75 years) and histologic subtypes. RESULTS: Temporal trends of incidence rates by sex, over the period 1985-2012, showed a distinct pattern. A significant change point of the trend was observed in males in 1994 (APC: +2.5%; 95% CI 0.7-4.4 from 1985 to 1994 and -1.4%; 95% CI -2.0 to -0.7 from 1994 onward). This general change was mainly caused by the age group 65-74 years and by the higher incidence of squamous cell carcinoma histologic subtype. In females, lung cancer incidence increased over the entire study period by +4.2% per year (95% CI 3.1-5.4); this trend was mainly caused by the age group 55-64 years (APC = +7%) and by adenocarcinoma incidence between women (APC = +6.8%). CONCLUSION: Male lung cancer incidence rates have decreased in Granada, while female rates have increased overall especially in younger women. These trends may reflect the increased consumption of cigarettes in women, especially during younger ages. Lung cancer prevention through tobacco control policies are therefore of utmost importance.

Photovoltaics: reviewing the European Feed-in-Tariffs and changing PV efficiencies and costs.

Feed-in-Tariff (FiT) mechanisms have been important in boosting renewable energy, by providing a long-term guaranteed subsidy of the kWh-price, thus mitigating investment risks and enhancing the contribution of sustainable electricity. By ongoing PV development, the contribution of solar power increases exponentially. Within this significant potential, it is important for investors, operators, and scientists alike to provide answers to different questions related to subsidies, PV efficiencies and costs. The present paper therefore (i) briefly reviews the mechanisms, advantages, and evolution of FiT; (ii) describes the developments of PV, (iii) applies a comprehensive literature-based model for the solar irradiation to predict the PV solar energy potential in some target European countries, whilst comparing output predictions with the monthly measured electricity generation of a 57 m² photovoltaic system (Belgium); and finally (iv) predicts the levelized cost of energy (LCOE) in terms of investment and efficiency, providing LCOE values between 0.149 and 0.313 €/kWh, as function of the overall process efficiency and cost. The findings clearly demonstrate the potential of PV energy in Europe, where FiT can be considerably reduced or even be eliminated in the near future.

Design of pharmaceutical products to meet future patient needs requires modification of current development paradigms and business models.

Drugs represent the most common intervention strategy for managing acute and chronic medical conditions. In light of demographic change and the increasing age of patients, the classic model of drug research and development by the pharmaceutical industry and drug prescription by physicians is reaching its limits. Different stakeholders, e.g. industry, regulatory authorities, health insurance systems, physicians etc., have at least partially differing interests regarding the process of healthcare provision. The primary responsibility for the correct handling of medication and adherence to treatment schedules lies with the recipient of a drug-based therapy, i.e. the patient. It is thus necessary to interactively involve elderly patients, as well as the other stakeholders, in the development of medication and medication application devices, and in clinical trials. This approach will provide the basis for developing a strategy that better meets patients' needs, thus resulting in improved adherence to treatment schedules and better therapeutic outcomes.

Sigma-1 receptor inhibition reverses acute inflammatory hyperalgesia in mice: role of peripheral sigma-1 receptors.

RATIONALE: Sigma-1 (σ1) receptor inhibition ameliorates neuropathic pain by inhibiting central sensitization. However, it is unknown whether σ1 receptor inhibition also decreases inflammatory hyperalgesia, or whether peripheral σ1 receptors are involved in this process. OBJECTIVE: The purpose of this study was to determine the role of σ1 receptors in carrageenan-induced inflammatory hyperalgesia, particularly at the inflammation site. RESULTS: The subcutaneous (s.c.) administration of the selective σ1 antagonists BD-1063 and S1RA to wild-type mice dose-dependently and fully reversed inflammatory mechanical (paw pressure) and thermal (radiant heat) hyperalgesia. These antihyperalgesic effects were abolished by the s.c. administration of the σ1 agonist PRE-084 and also by the intraplantar (i.pl.) administration of this compound in the inflamed paw, suggesting that blockade of peripheral σ1 receptors in the inflamed site is involved in the antihyperalgesic effects induced by σ1 antagonists. In fact, the i.pl. administration of σ1 antagonists in the inflamed paw (but not in the contralateral paw) was sufficient to completely reverse inflammatory hyperalgesia. σ1 knockout (σ1-KO) mice did not develop mechanical hyperalgesia but developed thermal hypersensitivity; however, the s.c. administration of BD-1063 or S1RA had no effect on thermal hyperalgesia in σ1-KO mice, supporting on-target mechanisms for the effects of both drugs. The antiedematous effects of σ1 inhibition do not account for the decreased hyperalgesia, since carrageenan-induced edema was unaffected by σ1 knockout or systemic σ1 pharmacological antagonism. CONCLUSIONS: σ1 receptors play a major role in inflammatory hyperalgesia. Targeting σ1 receptors in the inflamed tissue may be useful for the treatment of inflammatory pain.

Promoting access to innovation for frail old persons. IAGG (International Association of Gerontology and Geriatrics), WHO (World Health Organization) and SFGG (Société Française de Gériatrie et de Gérontologie) Workshop--Athens January 20-21, 2012.

UNLABELLED: Frailty tends to be considered as a major risk for adverse outcomes in older persons, but some important aspects remain matter of debate. OBJECTIVES: The purpose of this paper is to present expert's positions on the main aspects of the frailty syndrome in the older persons. PARTICIPANTS: Workshop organized by International Association of Gerontology and Geriatrics (IAGG), World Health Organization (WHO) and Société Française de Gériatrie et de Gérontologie (SFGG). RESULTS: Frailty is widely recognized as an important risk factor for adverse health outcomes in older persons. This can be of particular value in evaluating non-disabled older persons with chronic diseases but today no operational definition has been established. Nutritional status, mobility, activity, strength, endurance, cognition, and mood have been proposed as markers of frailty. Another approach calculates a multidimensional score ranging from "very fit" to "severely frail", but it is difficult to apply into the medical practice. Frailty appears to be secondary to multiple conditions using multiple pathways leading to a vulnerability to a stressor. Biological (inflammation, loss of hormones), clinical (sarcopenia, osteoporosis etc.), as well as social factors (isolation, financial situation) are involved in the vulnerability process. In clinical practice, detection of frailty is of major interest in oncology because of the high prevalence of cancer in older persons and the bad tolerance of the drug therapies. Presence of frailty should also be taken into account in the definition of the cardiovascular risks in the older population. The experts of the workshop have listed the points reached an agreement and those must to be a priority for improving understanding and use of frailty syndrome in practice. CONCLUSION: Frailty in older adults is a syndrome corresponding to a vulnerability to a stressor. Diagnostic tools have been developed but none can integrate at the same time the large spectrum of factors and the simplicity asked by the clinical practice. An agreement with an international common definition is necessary to develop screening and to reduce the morbidity in older persons.

Guidance synthesis. Medical research for and with older people in Europe: proposed ethical guidance for good clinical practice: ethical considerations.

INTRODUCTION: In Europe the population is ageing rapidly. Older people are taking many medicinal products daily and these may not necessarily be suitable for them. Publications show that older patients are underrepresented in clinical trials, especially those over 75 years, with multiple co-morbidities, concomitant treatments and/or frailty. This document provides a summary of recommendations on ethical aspects of clinical trials with older people, who may in some cases be considered a vulnerable patient population. The EFGCP's Geriatric Medicine Working Party (GMWP) has developed this guidance to promote such research and to support health care professionals in their efforts. ETHICAL, SCOPE AND CONTEXT: The definition of a geriatric patient is reviewed. Frail and vulnerable patients, who are a minority of geriatric patients, should be included whenever it is relevant. The legal context is described. THE PROCESS OF INFORMED CONSENT: All adults should be presumed capable of consent, unless proven otherwise; informed consent must be sought for all older people who are able to consent. A simple, short and easy-to-understand information sheet and consent form will contribute to improving the readability and understanding of the older participant. A participant guide and the use of a simple tool to ensure decision making capacity, are recommended. Whenever older people are unable to consent, their assent should be sought systematically using adequate information, in addition to seeking the consent of their legal or authorised representative as appropriate. ETHICS COMMITTEES: Research ethics committees need internal and/or external geriatric expertise to balance the benefits and risks of research in older people and to appreciate and recognise their autonomy. DESIGN AND ANALYSES: Design and Analyses should be adapted to the objectives with appropriate outcomes and are not different from other clinical trials. CONCLUSIONS: The absence of proper recruitment or insufficient presence of older patients in clinical development plans for new medicinal products is detrimental; there is a need to improve evidence-based knowledge, understanding and management of their conditions and treatment. The aim of this guidance is to facilitate clinical research for and with the older patient population. The long version of the guidance will be available on the EFGCP's website: www.efgcp.be/.

Intra-session test-retest reliability of pelvic floor muscle electromyography during running.

INTRODUCTION AND HYPOTHESIS: The prevalence of female stress urinary incontinence is high, and young adults are also affected, including athletes, especially those involved in "high-impact" sports. To date there have been almost no studies testing pelvic floor muscle (PFM) activity during dynamic functional whole body movements. The aim of this study was the description and reliability test of PFM activity and time variables during running. METHODS: A prospective cross-sectional study including ten healthy female subjects was designed with the focus on the intra-session test-retest reliability of PFM activity and time variables during running derived from electromyography (EMG) and accelerometry. RESULTS: Thirteen variables were identified based on ten steps of each subject: Six EMG variables showed good reliability (ICC 0.906-0.942) and seven time variables did not show good reliability (ICC 0.113-0.731). Time variables (e.g. time difference between heel strike and maximal acceleration of vaginal accelerator) showed low reliability. However, relevant PFM EMG variables during running (e.g., pre-activation, minimal and maximal activity) could be identified and showed good reliability. CONCLUSION: Further adaptations regarding measurement methods should be tested to gain better control of the kinetics and kinematics of the EMG probe and accelerometers. To our knowledge this is the first study to test the reliability of PFM activity and time variables during dynamic functional whole body movements. More knowledge of PFM activity and time variables may help to provide a deeper insight into physical strain with high force impacts and important functional reflexive contraction patterns of PFM to maintain or to restore continence.

Influence of the timing of ultrasound application on the penetration of corticosteroids.

BACKGROUND: The application of ultrasound to enhance the transdermal transport of drugs is often referred to as 'sonophoresis'. In physiotherapy sonophoresis is applied to the skin through two different procedures: (1) the pre-treatment procedure where the skin is treated with ultrasound irradiation prior to the drug application and (2) a simultaneous treatment mode, where the skin is treated with ultrasound during the application of the pharmacologic substance. The aim of this study was to compare the bioavailability of halcinonide in the stratum corneum comparing the ultrasound pre-treatment vs. the simultaneous treatment method. METHODS: The effect of pre and simultaneous ultrasound treatment (1 MHz, 1 W/cm(2)) was evaluated on the halcinonide blanching response using tristimulus colorimetry 2 h after the initial application. RESULTS: Within the evaluation period, only the ultrasound pre-treatment method resulted in a significant blanching response. CONCLUSION: Timing of the ultrasound application seems to influence the availability and percutaneous penetration process and should be taken into account when estimating the ultrasound enhancing effect.

In vivo measurement of the 3D kinematics of the temporomandibular joint using miniaturized electromagnetic trackers: technical report.

OBJECTIVE: The aim of this study was to evaluate the use of miniaturized electromagnetic trackers (1 × 0.5 × 0.5 cm) fixed on teeth of the maxilla and mandible to analyse in vivo the 3D kinematics of the temporomandibular joint (TMJ). A third sensor was fixed to the forehead, and a fourth sensor was used as a stylus pointer to detect several anatomical landmarks in order to embed a local frame on the cranium. Temporomandibular opening/closing, chewing, laterotrusion and protrusion were examined. RESULTS: The prime objective within this study was to rigidly attach electromagnetic minisensors on teeth. The key for a successful affixation was the kevlar interface. The distances between the two mandibular affixed sensors and between the two maxillar affixed sensors were overall smaller than 0.033 cm for position and 0.2° for attitude throughout the temporomandibular motions. The relative motions between a forehead sensor and the maxilla affixed sensor are too big to suggest a forehead sensor as an alternative for a maxilla affixed sensor. CONCLUSION: The technique using miniaturized electromagnetic trackers furthers on the methods using electromagnetic trackers on external appliances. The method allows full range of motion of the TMJ and does not disturb normal TMJ function.

Pharmacological properties of S1RA, a new sigma-1 receptor antagonist that inhibits neuropathic pain and activity-induced spinal sensitization.

BACKGROUND AND PURPOSE: The sigma-1 (σ(1) ) receptor is a ligand-regulated molecular chaperone that has been involved in pain, but there is limited understanding of the actions associated with its pharmacological modulation. Indeed, the selectivity and pharmacological properties of σ(1) receptor ligands used as pharmacological tools are unclear and the demonstration that σ(1) receptor antagonists have efficacy in reversing central sensitization-related pain sensitivity is still missing. EXPERIMENTAL APPROACH: The pharmacological properties of a novel σ(1) receptor antagonist (S1RA) were first characterized. S1RA was then used to investigate the effect of pharmacological antagonism of σ(1) receptors on in vivo nociception in sensitizing conditions and on in vitro spinal cord sensitization in mice. Drug levels and autoradiographic, ex vivo binding for σ(1) receptor occupancy were measured to substantiate behavioural data. KEY RESULTS: Formalin-induced nociception (both phases), capsaicin-induced mechanical hypersensitivity and sciatic nerve injury-induced mechanical and thermal hypersensitivity were dose-dependently inhibited by systemic administration of S1RA. Occupancy of σ(1) receptors in the CNS was significantly correlated with the antinociceptive effects. No pharmacodynamic tolerance to the antiallodynic and antihyperalgesic effect developed following repeated administration of S1RA to nerve-injured mice. As a mechanistic correlate, electrophysiological recordings demonstrated that pharmacological antagonism of σ(1) receptors attenuated the wind-up responses in spinal cords sensitized by repetitive nociceptive stimulation. CONCLUSIONS AND IMPLICATIONS: These findings contribute to evidence identifying the σ(1) receptor as a modulator of activity-induced spinal sensitization and pain hypersensitivity, and suggest σ(1) receptor antagonists as potential novel treatments for neuropathic pain.

Continuous versus intermittent stochastic resonance whole body vibration and its effect on pelvic floor muscle activity.

AIMS: To determine the optimal stochastic whole body vibration (SR-WBV) load modality regarding pelvic floor muscle (PFM) activity in order to complete the SR-WBV training methodology for future PFM training with SR-WBV. METHODS: The continuous and the intermittent SR-WBV modalities were tested by means of electromyography in two independent groups (27 women 8 weeks to 1-year postpartum and 23 women nulliparae or >1-year postpartum) with self-reported stress urinary incontinence. The change in the PFM activity within a single set and over three sets were calculated for both SR-WBV modalities together (time effect) and for both SR-WBV modalities separately (modality-time interaction). RESULTS: There was no statistically significant or clinically relevant change in PFM activity over time or PFM fatigue in either SR-WBV modality within one or three sets and no difference between the modalities or the groups. CONCLUSIONS: The lack of change in PFM activity could be due to a no more than moderate to submaximal PFM activity during SR-WBV, the maintenance of reflexive PFM activity despite PFM fatigue or a compensation of slow red PFM fiber fatigue by an increase of innervation frequency and motor unit recruitment of the fast white fibers. As there is no SR-WBV modality dependent difference regarding PFM activity, the continuous modality is recommended in clinical practice as it is easier to apply and less time consuming.

IAGG workshop: health promotion program on prevention of late onset dementia.

IAGG, WHO, and SFGG organized a international workshop on Health promotion programs on prevention of late on-set dementia. Thirty world specialists coming from Europe, North America, Asia, South America, Africa and Australia, shared their experience on methods and results of large epidemiological interventions to reduce incidents of dementia or delay its on-set. Chaired by Laura FRATIGLIONI, an expert in Epidemiological studies on dementia issues, the workshop gave opportunity for discussions and controversies about the state-of-the-art. Based on different national and international trials (ADAPT, MAPT, FINGER, GUDIAGE, GEM etc) the questions remained opened for different aspects of methodology, the choice of domain or multi domain intervention, the choice and the definition of the target populations, the best age of candidates, the issues related to the discrepancy between late effects, and interventions' duration. We are please to publish in the Journal, the presentations presented to this workshop. These publications will complete previously task force published in the journal in the last two years on methodological issues for Alzheimer's trials including end point, biomarkers, and the experience of past therapeutic trials.

Scapular positioning and movement in unimpaired shoulders, shoulder impingement syndrome, and glenohumeral instability.

The purpose of this manuscript is to review the knowledge of scapular positioning at rest and scapular movement in different anatomic planes in asymptomatic subjects and patients with shoulder impingement syndrome (SIS) and glenohumeral shoulder instability. We reviewed the literature for all biomechanical and kinematic studies using keywords for impingement syndrome, shoulder instability, and scapular movement published in peer reviewed journal. Based on the predefined inclusion and exclusion criteria, 30 articles were selected for inclusion in the review. The literature is inconsistent regarding the scapular resting position. At rest, the scapula is positioned approximately horizontal, 35° of internal rotation and 10° anterior tilt. During shoulder elevation, most researchers agree that the scapula tilts posteriorly and rotates both upward and externally. It appears that during shoulder elevation, patients with SIS demonstrate a decreased upward scapular rotation, a decreased posterior tilt, and a decrease in external rotation. In patients with glenohumeral shoulder instability, a decreased scapular upward rotation and increased internal rotation is seen. This literature overview provides clinicians with insight into scapular kinematics in unimpaired shoulders and shoulders with impingement syndrome and instability.

Automotive shredder residue (ASR): reviewing its production from end-of-life vehicles (ELVs) and its recycling, energy or chemicals' valorisation.

ASR is in Europe classified as hazardous waste. Both the stringent landfill legislation and the objectives/legislation related to ELV treatment of various countries, will limit current landfilling practice and impose an increased efficiency of the recovery and recycling of ELVs. The present paper situates ASR within the ELV context. Primary recovery techniques recycle up to 75% of the ELV components; the remaining 25% is called ASR. Characteristics of ASR and possible upgrading by secondary recovery techniques are reviewed. The latter techniques can produce a fuel- or fillergrade ASR, however with limitations as discussed. A further reduction of ASR to be disposed of calls upon (co-)incineration or the use of thermo-chemical processes, such as pyrolysis or gasification. The application in waste-to-energy plants, in cement kilns or in metallurgical processes is possible, with attention to the possible environmental impact: research into these impacts is discussed in detail. Pyrolysis and gasification are emerging technologies: although the sole use of ASR is debatable, its mixing with other waste streams is gradually being applied in commercial processes. The environmental impacts of the processes are acceptable, but more supporting data are needed and the advantage over (co-)incineration remains to be proven.