Performance of predictive tools to identify individuals at risk of non-traumatic fracture: a systematic review, meta-analysis, and meta-regression.

There is no consensus on which tool is the most accurate to assess fracture risk. The results of this systematic review suggest that QFracture, Fracture Risk Assessment Tool (FRAX) with BMD, and Garvan with BMD are the tools with the best discriminative ability. More studies assessing the comparative performance of current tools are needed. INTRODUCTION: Many tools exist to assess fracture risk. This review aims to determine which tools have the best predictive accuracy to identify individuals at high risk of non-traumatic fracture. METHODS: Studies assessing the accuracy of tools for prediction of fracture were searched in MEDLINE, EMBASE, Evidence-Based Medicine Reviews, and Global Health. Studies were eligible if discrimination was assessed in a population independent of the derivation cohort. Meta-analyses and meta-regressions were performed on areas under the ROC curve (AUCs). Gender, mean age, age range, and study quality were used as adjustment variables. RESULTS: We identified 53 validation studies assessing the discriminative ability of 14 tools. Given the small number of studies on some tools, only FRAX, Garvan, and QFracture were compared using meta-regression models. In the unadjusted analyses, QFracture had the best discriminative ability to predict hip fracture (AUC = 0.88). In the adjusted analysis, FRAX with BMD (AUC = 0.81) and Garvan with BMD (AUC = 0.79) had the highest AUCs. For prediction of major osteoporotic fracture, QFracture had the best discriminative ability (AUC = 0.77). For prediction of osteoporotic or any fracture, FRAX with BMD and Garvan with BMD had higher discriminative ability than their versions without BMD (FRAX: AUC = 0.72 vs 0.69, Garvan: AUC = 0.72 vs 0.65). A significant amount of heterogeneity was present in the analyses. CONCLUSIONS: QFracture, FRAX with BMD, and Garvan with BMD have the highest discriminative performance for predicting fracture. Additional studies in which the performance of current tools is assessed in the same individuals may be performed to confirm this conclusion.

Medication recommendation by physiotherapists: A survey of Québec physiotherapists' opinions regarding a new interprofessional model of care with pharmacists.

BACKGROUND: To improve the efficiency of the health care system, new interprofessional models of care are emerging. In 2015, two provincial professional colleges, regulating the practice of physiotherapists and that of pharmacists in the province of Québec, Canada, developed a new interprofessional model of care. This model is designed to guide non-prescription medication recommendations by physiotherapists treating patients in primary care with neuromusculoskeletal disorders (NMSKD) with the collaboration of pharmacists. PURPOSE: To assess Québec physiotherapists' interests to use this model and explore their opinions concerning their ability to recommend non-prescription medications to patients in primary care with NMSKD. METHODS: An email invitation to complete an electronic survey was sent in February 2016 to all the Ordre professionnel de la physiothérapie du Québec's registered physiotherapists. The survey included a questionnaire with 31 questions divided into 5 sections. Descriptive analyses and Chi-square tests (χ2 ) were performed to compare proportions (%) across demographic and clinical characteristics. RESULTS: Two hundred twenty-five physiotherapists completed the full survey. Of these, 70% of respondents knew of the model of care, but only 15% had previously used it. Perceived workload increase was one major reason reported for this lack of use (51%). Most of the respondents had a positive perception of this model and interactions with pharmacists and were confident regarding their ability to safely recommend medication (63%). However, 63% believed that further training was necessary to enable physiotherapists to provide efficient and safe non-prescription medication recommendations to patients with NMSKD. CONCLUSIONS: Overall, physiotherapists have a positive perception of this model, but there remain opportunities for increased integration into practice. Most respondents believe that additional training is required regarding non-prescription medication recommendations.

Sex-specific association between obesity and self-reported falls and injuries among community-dwelling Canadians aged 65 years and older.

This study investigated the relationship between body mass index (BMI) and falls among community-dwelling elderly. Results indicate that obesity is associated with increased falls and there appears to be a sex-specific difference with obese men at higher risk of falling. Obesity is identified as a risk factor for falls in men. INTRODUCTION: The prevalence of falls, fall-related injuries, and obesity has increased over the last decade. The objectives of this study were to investigate sex-specific association and dose-response relationship between BMI and falls (and related injuries) among community-dwelling elderly. METHODS: Our study sample consisted of 15,860 adults aged 65 years or older (6399 men and 9461 women) from the 2008-2009 Canadian Community Health Survey-Healthy Aging (CCHS-HA). Falls, fall-related injuries, and BMI measures were self-reported. For both sex, dose-response curves presenting the relationship between BMI, falls, and fall-related injuries were first examined. Thereafter, multivariate logistic regression analyses were also performed to investigate these relationships after adjustment for potentially confounding variables. RESULTS: Of women, 21.7 % reported a fall and 16.9 % of men. The dose-response relationship between BMI and prevalence of falls showed that underweight and obese individuals reported falling more than normal and overweight individuals; this being more apparent in men than women. Finally, the dose relationship between BMI and prevalence of fall-related injuries showed that only obese men seem more likely to have sustained a fall-related injury. Results from the multivariate analysis showed that obesity in men was significantly associated with higher odds of falling odds ratio (OR) 1.33 (1.04-1.70) and was not significantly associated with higher odds of fall-related injuries OR 1.10 (0.66-1.84) over a 12-month period compared to normal weight men. For women, obesity was not significantly associated with higher fall prevalence OR 0.99 (0.79-1.25) and fall-related injuries OR 0.71 (0.51-1.00). CONCLUSION: Obesity is associated with self-reported falls, and there appears to be a sex-specific difference in elderly persons.

Impact of online visual feedback on motor acquisition and retention when learning to reach in a force field.

When subjects learn a novel motor task, several sources of feedback (proprioceptive, visual or auditory) contribute to the performance. Over the past few years, several studies have investigated the role of visual feedback in motor learning, yet evidence remains conflicting. The aim of this study was therefore to investigate the role of online visual feedback (VFb) on the acquisition and retention stages of motor learning associated with training in a reaching task. Thirty healthy subjects made ballistic reaching movements with their dominant arm toward two targets, on 2 consecutive days using a robotized exoskeleton (KINARM). They were randomly assigned to a group with (VFb) or without (NoVFb) VFb of index position during movement. On day 1, the task was performed before (baseline) and during the application of a velocity-dependent resistive force field (adaptation). To assess retention, participants repeated the task with the force field on day 2. Motor learning was characterized by: (1) the final endpoint error (movement accuracy) and (2) the initial angle (iANG) of deviation (motor planning). Even though both groups showed motor adaptation, the NoVFb-group exhibited slower learning and higher final endpoint error than the VFb-group. In some condition, subjects trained without visual feedback used more curved initial trajectories to anticipate for the perturbation. This observation suggests that learning to reach targets in a velocity-dependent resistive force field is possible even when feedback is limited. However, the absence of VFb leads to different strategies that were only apparent when reaching toward the most challenging target.

Experimental tonic hand pain modulates the corticospinal plasticity induced by a subsequent hand deafferentation.

Sensorimotor reorganization is believed to play an important role in the development and maintenance of phantom limb pain, but pain itself might modulate sensorimotor plasticity induced by deafferentation. Clinical and basic research support this idea, as pain prior to amputation increases the risk of developing post-amputation pain. The aim of this study was to examine the influence of experimental tonic cutaneous hand pain on the plasticity induced by temporary ischemic hand deafferentation. Sixteen healthy subjects participated in two experimental sessions (Pain, No Pain) in which transcranial magnetic stimulation was used to assess corticospinal excitability in two forearm muscles (flexor carpi radialis and flexor digitorum superficialis) before (T0, T10, T20, and T40) and after (T60 and T75) inflation of a cuff around the wrist. The cuff was inflated at T45 in both sessions and in the Pain session capsaicin cream was applied on the dorsum of the hand at T5. Corticospinal excitability was significantly greater during the Post-inflation phase (p=0.002) and increased similarly in both muscles (p=0.861). Importantly, the excitability increase in the Post-inflation phase was greater for the Pain than the No-Pain condition (p=0.006). Post-hoc analyses revealed a significant difference between the two conditions during the Post-inflation phase (p=0.030) but no difference during the Pre-inflation phase (p=0.601). In other words, the corticospinal facilitation was greater when pain was present prior to cuff inflation. These results indicate that pain can modulate the plasticity induced by another event, and could partially explain the sensorimotor reorganization often reported in chronic pain populations.

Cross-strand histidine-aromatic interactions enhance acyl-transfer rates in beta-hairpin peptide catalysts.

A reactive tagging methodology was used to select the species most reactive to an acylation reagent from a solid phase library of beta hairpin peptides. Hits bearing an electron-rich aromatic residue across strand from a reactive histidine were found to competitively become N-acylated. In addition to displaying rapid N-acylation rates the hit peptide was additionally deacylated in the presence of a nucleophile, thus closing a putative catalytic cycle. Variants of the hit peptide were studied to elucidate both the magnitude (up to 18,000-fold over background, kcat/kuncat = 94,000,000, or 45-fold over Boc-histidine methyl ester) and mechanism of acyl transfer catalysis. A combination of CH-π, cation-π and HisH(+)-O interactions in the cationic imidazole transition state is implicated in the rate acceleration, in addition to the fidelity of the beta hairpin fold. Moreover, NMR structural data on key intermediates or models thereof suggest that a key feature of this catalyst is the ability to access several different stabilizing conformations along the catalysis reaction coordinate.

Changes in fall-related mortality in older adults in Quebec, 1981-2009.

INTRODUCTION: Our purpose was to evaluate changes in fall-related mortality in adults aged 65 years and over in Quebec and to propose a case definition based on all the causes entered on Return of Death forms. METHODS: The analysis covers deaths between 1981 and 2009 recorded in the Quebec vital statistics data. RESULTS: While the number of fall-related deaths increased between 1981 and 2009, the adjusted falls-related mortality rate remained relatively stable. Since the early 2000s, this stability has masked opposing trends. The mortality rate associated with certified falls (W00-W19) has increased while the rate for presumed falls (exposure to an unspecified factor causing a fracture) has decreased. CONCLUSION: For fall surveillance, analyses using indicators from the vital statistics data should include both certified falls and presumed falls. In addition, a possible shift in the coding of fall-related deaths toward secondary causes should be taken into account.

TITRE: Évolution de la mortalité associée aux chutes chez les personnes âgées au Québec, 1981 à 2009. INTRODUCTION: Cette étude a pour objectif d'apprécier l'évolution de la mortalité associée aux chutes chez les adultes de 65 ans et plus au Québec et de proposer une définition de cas reposant sur l'ensemble des causes inscrites sur les bulletins de décès. MÉTHODOLOGIE: L'analyse porte sur les décès survenus entre 1981 et 2009, enregistrés dans le fichier des décès québécois. RÉSULTATS: Bien que le nombre de décès reliés à une chute se soit accru entre 1981 et 2009, le taux ajusté de mortalité associée aux chutes est demeuré relativement stable. Depuis le début des années 2000, cette stabilité camoufle des tendances opposées. Le taux de mortalité associé aux chutes certifiées (W00-W19) s'est accru, alors que celui associé aux chutes présumées (exposition à un facteur non précisé causant une fracture) s'est réduit. CONCLUSION: Pour la surveillance des chutes, les analyses effectuées à l'aide d'indicateurs utilisant le fichier des décès devraient inclure ces deux catégories. Par ailleurs, un glissement possible de la codification des décès dus aux chutes vers les causes secondaires devrait être pris en compte.

Delivery of proteins to CNS as seen and measured by positron emission tomography.

Presently, there are no effective treatments for several diseases involving the central nervous system (CNS). While several novel molecular approaches are being developed, many of them require delivery of macromolecular or supramolecular agents to the CNS tissues protected by the blood-brain and blood-arachnoid barriers. A variety of approaches that are being developed for overcoming or bypassing the barriers are based on complex transfer processes. The delivery of biopharmaceuticals and other macromolecules and particulates to the CNS, especially through the leptomeningeal (intrathecal) route, includes a variety of stages, such as leptomeningeal propagation, drainage to the systemic circulation, and penetration into the CNS. The investigation of complex pharmacokinetics that includes convective, as well as diffusional and active transfer processes, greatly benefit from real-time non-invasive in vivo monitoring of the drug transport. Pharmacological positron emission tomography (PET) imaging, which enables such monitoring, plays an increasingly significant role in drug delivery and biopharmacology. PET is a powerful tool for quantitative in vivo tracking of molecules labeled with positron-emitting radionuclides. The high sensitivity, format, and accuracy of the data (similar to those of conventional tissue sampling biodistribution studies) make PET a readily adoptable pharmacological technique. In contrast to the conventional studies, PET also allows for longitudinal nonterminal same-animal studies. The latter may not only improve the data statistics, but also enable preclinical studies (especially in large and/or rare animals) not feasible under the conventional approach. This paper is intended to demonstrate the character of data that can be obtained by PET and to demonstrate how the main patterns of the leptomeningeal route pharmacokinetics can be investigated using this method. Examples of data processing are taken from our recent studies of five model proteins in rats and nonhuman primates.

Investigation of intrathecal transport of NPT002, a prospective therapeutic based on phage M13, in nonhuman primates.

Presently, there are no effective treatments for conditions characterized by protein misfolding, such as Alzheimer's, Parkinson's, and other diseases involving CNS. Since misfolding occurs at the earliest stage of the disease, it is likely to be involved in subsequent pathological developments. It has been found that NPT002 (bacteriophage M13) directly dissociates aggregates of misfolded proteins that form amyloid, including amyloid-ß, tau and α-synuclein. For CNS applications, NPT002 requires delivery to the brain parenchyma, the target tissue. NPT002 is an elongated ~950 nm particle that cannot penetrate into the brain from the blood. Furthermore, phage particles, due to their size, cannot be effectively transported in vivo by diffusion. Considering the physiology of the leptomeningeal space, intrathecal administration appears to be a promising convection-driven avenue for NPT002 delivery. In this paper, we use positron emission tomography to investigate the transport of NPT002 in Macaca fascicularis. The data suggest that approximately 50 % of the administered dose can reach the cerebral leptomeningeal space after a single lumbar intrathecal injection. A biologically significant fraction of the phage then enters the brain, resulting in potentially therapeutic cortical and subcortical exposure.

Short-term reliability of transcranial magnetic stimulation motor maps in upper limb amputees.

The aim of this study was to verify the short-term reliability of transcranial magnetic stimulation (TMS) parameters for a damaged stump muscle in upper-limb amputees (n=6). The motor threshold, response latency and map center of gravity in the mediolateral plane showed good reliability, whereas the map volume measure was less stable. The stability of most TMS measures across time supports the use of TMS in studying cortical plasticity in amputees.

[Destruction of a penile urethra resulting from a snake bite: Uretroplasty using inguinal flap of Mac Gregor]. / Destruction de l'urètre pénien consécutive à une morsure de serpent : urétroplastie par le lambeau inguinal de Mac Gregor.

Following a snake bite to the penis, a 69 years old man presented a large defect of hemicircumferential ventral penis, destroying the penile urethra along its entire length exposing the erectile bodies. The authors proposed a two-stage reconstruction of the urethra with an inguinal axial pedicle flap of Mac Gregor. This well-vascularized flap thick after degreasing helped repair the penile urethra along its entire length and make up losses of substance with a good functional and aesthetic result.

Positional cloning of a quantitative trait locus contributing to pain sensitivity: possible mediation by Tyrp1.

To identify novel pain-relevant genes, a set of 35 recombinant congenic strains derived from the sensitive C57BL/6 and resistant A/J strains were tested for their sensitivity to noxious heat on the radiant heat paw-withdrawal test. Nine strains were found to display differential sensitivity, and the two most extreme responders were used to generate independent secondary crosses for quantitative trait locus (QTL) mapping. From these genetic analyses, a QTL, which we call Tpnr5, was mapped to a 14-Mb interval of mouse chromosome 4 containing 39 genes. In addition to the paw-withdrawal test phenotype, Tpnr5 may be relevant to mechanical and inflammatory nociception. A series of strategies - including in silico analyses, reverse transcriptase polymerase chain reaction (RT-PCR) in multiple tissues and exonic DNA sequencing - were used to generate a list of six prioritized candidate genes. One of these, tyrosinase-related protein 1 (Tyrp1), displayed enriched expression in the dorsal root ganglia, an inactivating (C110Y) mutation in the resistant A/J strain, and a null mutant found to be more resistant to thermal nociception compared to its wild-type counterpart. Although other genes cannot be definitively ruled out, existing data are supportive of the candidacy of Tyrp1 as representing the Tpnr5 QTL. Tyrosinase-related protein 1 is the rate-limiting enzyme in the production of eumelanin, and possible relationships between eumelanin-expressing cells and thermal nociception are discussed. The positional cloning of Tpnr5 is also considered in light of the heuristic value but continuing challenges of QTL mapping in the mouse.

Variability in the effector-specific pattern of motor facilitation during the observation of everyday actions: implications for the clinical use of action observation.

Action observation is increasingly considered as a rehabilitation tool as it can increase the cortical excitability of muscles involved in the observed movements and therefore produce effector-specific motor facilitation. In order to investigate the action observation mechanisms, simple single joint intransitive movements have commonly been used. Still, how the observation of everyday movements which often are the prime target of rehabilitation affects the observer cortical excitability remains unclear. Using transcranial magnetic stimulations, we aimed at verifying if the observation of everyday movements made by the proximal or distal upper-limb produces effector-specific motor facilitation in proximal (arm) and distal (hand) muscles of healthy subjects. Results suggest that, similar to simple intransitive movements, observation of more complex everyday movements involving mainly the proximal or distal part of upper limb induces different patterns of motor facilitation across upper limb muscles (P=0.02). However, we observed large inter-individual variability in the strength of the effector-specific motor facilitation induced by action observation. Yet, subjects had similar types of response (strong or weak effector-specific effects) when watching proximal or distal movements indicating that the facilitation pattern was highly consistent within subjects (r=0.83-0.88, P<0.001). This suggests that some individuals are better than other at precisely mapping the observed movements on their motor repertoire and that this type of response holds for various types of everyday actions.

Development of a real-time TaqMan PCR assay for the detection of porcine and bovine Torque teno virus.

AIMS: The goal of this study was to develop and to optimize molecular tools to detect the presence of Torque teno virus (TTV) in swine and cattle. A novel real-time polymerase chain reaction (PCR) using a TaqMan probe was developed to detect both genogroups of TTV strains. METHODS AND RESULTS: Oligonucleotide primers and hybridization probes were designed based on sequence analysis of the noncoding region, a highly conserved part of the genome. The real-time PCR assay specifically detected bovine and porcine TTV DNA without cross-amplification of other common pathogens. The assay was compared with conventional PCR and nested-PCR assays for the detection of porcine genogroups 1 and 2 and bovine TTV on plasma and faecal samples, and the assay was found faster, more reliable and reduced the risk of false positive results. CONCLUSIONS: The real-time PCR assay provided better detection results for the two TTV genogroups in both swine and cattle compared to the conventional PCR assays. SIGNIFICANCE AND IMPACT OF THE STUDY: This new TaqMan PCR assay will be a useful tool for the detection of animal TTV strains, to evaluate the viral load from animal host and finally to identify the presence of these viruses in the agri-food continuum.

The effect of pre-treatment and sonication of centrifugal ultrafiltration devices on virus recovery.

Enteric viruses such as norovirus (NV) and hepatitis A (HAV) are responsible for a large proportion of food and water-borne illnesses. Most human pathogenic enteric viruses cannot be cultured so they must be detected by molecular techniques. Male specific (F(+)) RNA coliphages, a potential surrogate for human enteric viruses, can be detected by culture and molecular assays. Numbers of viruses and F-RNA coliphages in contaminated food or water may be too low for direct detection. Ultrafiltration is a general concentration method for all virus types but there is little information on the recovery efficiency of F-RNA coliphages and enteric viruses. The recovery of F-RNA coliphage MS2 was only 25% by plaque assay in initial trials. The objective was to optimize the recovery of concentrated MS2 from Microsep 100K ultrafiltration devices. The mean recovery of MS2 increased significantly to 85% by plaque assay and 65% by real-time RT-PCR when ultrafiltration devices were treated with 1% BSA before concentration and then ultrasonicated after concentration. The method was validated with MS2, HAV, NV and feline calicivirus (FCV) in water and spinach eluate. The recovery of MS2, HAV and NV was significantly higher from concentrates obtained from water with treated devices than untreated devices but not significantly different for FCV or from spinach eluate. To our knowledge, this is the first study to use ultrasonication as a post-treatment step to increase recovery of viruses from ultrafiltration devices.

Motor control over the phantom limb in above-elbow amputees and its relationship with phantom limb pain.

Recent evidence shows that the primary motor cortex continues to send motor commands when amputees execute phantom movements. These commands are retargeted toward the remaining stump muscles as a result of motor system reorganization. As amputation-induced reorganization in the primary motor cortex has been associated with phantom limb pain we hypothesized that the motor control of the phantom limb would differ between amputees with and without phantom limb pain. Eight above-elbow amputees with or without pain were included in the study. They were asked to produce cyclic movements with their phantom limb (hand, wrist, and elbow movements) while simultaneously reproducing the same movement with the intact limb. The time needed to complete a movement cycle and its amplitude were derived from the kinematics of the intact limb. Electromyographic (EMG) activity from different stump muscles and from the homologous muscles on the intact side was recorded. Different EMG patterns were recorded in the stump muscles depending on the movement produced, showing that different phantom movements are associated with distinct motor commands. Phantom limb pain was associated with some aspects of phantom limb motor control. The time needed to complete a full cycle of a phantom movement was systematically shorter in subjects without phantom limb pain. Also, the amount of EMG modulation recorded in a stump muscle during a phantom hand movement was positively correlated with the intensity of phantom limb pain. Since phantom hand movement-related EMG patterns in above-elbow stump muscles can be considered as a marker of motor system reorganization, this result indirectly supports the hypothesis that amputation-induced plasticity is associated with phantom limb pain severity. The discordance between the (amputated) hand motor command and the feedback from above-elbow muscles might partially explain why subjects exhibiting large EMG modulation during phantom hand movement have more phantom limb pain.

The F13 residue is critical for interaction among the coat protein subunits of papaya mosaic virus.

Papaya mosaic virus (PapMV) coat protein (CP) in Escherichia coli was previously showed to self-assemble in nucleocapsid-like particles (NLPs) that were similar in shape and appearance to the native virus. We have also shown that a truncated CP missing the N-terminal 26 amino acids is monomeric and loses its ability to bind RNA. It is likely that the N-terminus of the CP is important for the interaction between the subunits in self-assembly into NLPs. In this work, through deletion and mutation analysis, we have shown that the deletion of 13 amino acids is sufficient to generate the monomeric form of the CP. Furthermore, we have shown that residue F13 is critical for self-assembly of the CP subunits into NLPs. The replacement of F13 with hydrophobic residues (L or Y) generated mutated forms of the CP that were able to self-assemble into NLPs. However, the replacement of F13 by A, G, R, E or S was detrimental to the self-assembly of the protein into NLPs. We concluded that a hydrophobic interaction at the N-terminus is important to ensure self-assembly of the protein into NLPs. We also discuss the importance of F13 for assembly of other members of the potexvirus family.

Molecular detection of bovine and porcine Torque teno virus in plasma and feces.

Torque teno virus (TTV) is frequently detected in humans, livestock and some companion animals. Very little is known about presence of TTV in Canadian livestock and the goal of this study was to evaluate the presence of TTV in swine and cattle using molecular tools. TTV DNA was detected and confirmed by sequencing in the plasma of 90.5% and in the feces of 60.3% of the animals tested in a single swine herd as well as 80.9% and 1.1% in the plasma of individuals from general Quebec swine and cattle populations, respectively. The impact of the TTV presence in livestock population for the agri-food chain should be further investigated.

Structure and reactivity of mixed alkali metal alkoxide/aryloxide catalysts.

The average solution aggregation state of the ester interchange catalyst 1, obtained by mixing 1 equiv of NaOt-Bu and 3 equiv of NaOC(6)H(4)-4-t-Bu, was determined to be 4.0 by vapor pressure osmometry (VPO) in THF. Low-temperature (1)H NMR spectra of 1 indicated that the THF solution contained a mixture of tetrameric clusters. On the basis of symmetry arguments and the sensitivity of the different species to the alkoxide/aryloxide ratio, the compounds were determined to be mixed clusters with 0:4, 1:3, 2:2, and 3:1 mixtures of the NaOt-Bu and NaOC(6)H(4)-4-t-Bu components. On a per -Ot-Bu basis, each cluster has a similar absolute activity, though the aryloxide-rich catalysts are significantly longer-lived. Unlike 1, catalysts containing ortho-substituted aryloxides, 2, do not give a strictly statistical distribution of clusters, and the activities of these catalysts depend on steric and electronic factors, though the absolute rate differences are not large.