The effect of targeted treatment on people with patellofemoral pain: A pragmatic, randomised controlled feasibility study

Background: Targeted treatment, matched according to specific clinical criteria e.g. hip muscle weakness, may result in better outcomes for people with patellofemoral pain (PFP). However, to ensure the success of future trials, a number of questions on the feasibility of a targeted treatment need clarification. The aim of the study was to explore the feasibility of matched treatment (MT) compared to usual care (UC) management for a subgroup of people with PFP determined to have hip weakness and to explore the mechanism of effect for hip strengthening. Methods: In a pragmatic, randomised controlled feasibility study, 24 participants with PFP (58% female; mean age 29 years) were randomly allocated to receive either MT aimed specifically at hip strengthening, or UC over an eight-week period. The primary outcomes were feasibility outcomes, which included rates of adherence, attrition, eligibility, missing data and treatment efficacy. Secondary outcomes focused on the mechanistic outcomes of the intervention, which included hip kinematics. Results: Conversion to consent (100%), missing data (0%), attrition rate (8%) and adherence to both treatment and appointments ( > 90%) were deemed successful endpoints. The analysis of treatment efficacy showed that the MT group reported a greater improvement for the Global Rating of Change Scale (62% vs. 9%) and the Anterior Knee Pain Scale (-5.23 vs. 1.18) but no between-group differences for either average or worst pain. Mechanistic outcomes showed a greatest reduction in peak hip internal rotation angle for the MT group (13.1% vs. -2.7%). Conclusion: This feasibility study indicates that a definitive randomised controlled trial investigating a targeted treatment approach is achievable. Findings suggest the mechanism of effect of hip strengthening may be to influence kinematic changes in hip function in the transverse plane

Patellofemoral morphology is not related to pain using three-dimensional quantitative analysis in an older population: data from the Osteoarthritis Initiative

Objectives: Current structural associations of patellofemoral pain (PFP) are based on 2D imaging methodology with inherent measurement uncertainty due to positioning and rotation. This study employed novel technology to create 3D measures of commonly described patellofemoral joint imaging features and compared these features in people with and without PFP in a large cohort. Methods: We compared two groups from the Osteoarthritis Initiative: one with localized PFP and pain on stairs, and a control group with no knee pain; both groups had no radiographic OA. MRI bone surfaces were automatically segmented and aligned using active appearance models. We applied t-tests, logistic regression and linear discriminant analysis to compare 13 imaging features (including patella position, trochlear morphology, facet area and tilt) converted into 3D equivalents, and a measure of overall 3D shape. Results: One hundred and fifteen knees with PFP (mean age 59.7, BMI 27.5 kg/m², female 58.2%) and 438 without PFP (mean age 63.6, BMI 26.9 kg/m², female 52.9%) were included. After correction for multiple testing, no statistically significant differences were found between groups for any of the 3D imaging features or their combinations. A statistically significant discrimination was noted for overall 3D shape between genders, confirming the validity of the 3D measures. Conclusion: Challenging current perceptions, no differences in patellofemoral morphology were found between older people with and without PFP using 3D quantitative imaging analysis. Further work is needed to see if these findings are replicated in a younger PFP population

The Meissner effect in a strongly underdoped cuprate above its critical temperature

The Meissner effect and the associated perfect "bulk" diamagnetism together with zero resistance and gap opening are characteristic features of the superconducting state. In the pseudogap state of cuprates unusual diamagnetic signals as well as anomalous proximity effects have been detected but a Meissner effect has never been observed. Here we have probed the local diamagnetic response in the normal state of an underdoped La1.94Sr0.06CuO4 layer (up to 46 nm thick, critical temperature Tc' < 5 K) which was brought into close contact with two nearly optimally doped La1.84Sr0.16CuO4 layers (Tc \approx 32 K). We show that the entire 'barrier' layer of thickness much larger than the typical c axis coherence lengths of cuprates exhibits a Meissner effect at temperatures well above Tc' but below Tc. The temperature dependence of the effective penetration depth and superfluid density in different layers indicates that superfluidity with long-range phase coherence is induced in the underdoped layer by the proximity to optimally doped layers; however, this induced order is very sensitive to thermal excitation.Comment: 7 pages, 7 figures + Erratu

Worm Grunting, Fiddling, and Charming—Humans Unknowingly Mimic a Predator to Harvest Bait

Background: For generations many families in and around Florida’s Apalachicola National Forest have supported themselves by collecting the large endemic earthworms (Diplocardia mississippiensis). This is accomplished by vibrating a wooden stake driven into the soil, a practice called ‘‘worm grunting’’. In response to the vibrations, worms emerge to the surface where thousands can be gathered in a few hours. Why do these earthworms suddenly exit their burrows in response to vibrations, exposing themselves to predation? Principal Findings: Here it is shown that a population of eastern American moles (Scalopus aquaticus) inhabits the area where worms are collected and that earthworms have a pronounced escape response from moles consisting of rapidly exiting their burrows to flee across the soil surface. Recordings of vibrations generated by bait collectors and moles suggest that ‘‘worm grunters’ ’ unknowingly mimic digging moles. An alternative possibility, that worms interpret vibrations as rain and surface to avoid drowning is not supported. Conclusions: Previous investigations have revealed that both wood turtles and herring gulls vibrate the ground to elicit earthworm escapes, indicating that a range of predators may exploit the predator-prey relationship between earthworms and moles. In addition to revealing a novel escape response that may be widespread among soil fauna, the results sho

Modulation of Antimalarial Activity at a Putative Bisquinoline Receptor in vivo Using Fluorinated Bisquinolines

Antimalarials can interact with heme covalently, by - interactions or hydrogen bonding. Consequently, the prototropy of 4-aminoquinolines and quinoline methanols was investigated using quantum mechanics. Calculations showed mefloquine protonated preferentially at the piperidine and was impeded at the endocyclic nitrogen due to electronic rather than steric factors. In gas phase calculations, 7-substituted mono- and bis-4-aminoquinolines were preferentially protonated at the endocyclic quinoline nitrogen. By contrast, compounds with a trifluoromethyl substituent on both the 2- and 8-positions, reversed the order of protonation which now favored the exocyclic secondary amine nitrogen at the 4-position. Loss of antimalarial efficacy by CF3 groups simultaneously occupying the 2- and 8-positions was recovered if the CF3 group occupied the 7-position. Hence, trifluromethyl groups buttressing quinolinyl nitrogen shifted binding of antimalarials to hematin, enabling switching from endocyclic to the exocyclic N. Both theoretical calculations (DFT calculations: B3LYP/6- 31+G*) and crystal structure of (±)-trans-N1,N2-bis-(2,8-ditrifluoromethylquinolin-4- yl)cyclohexane-1,2-diamine were used to reveal preferred mode(s) of interaction with hematin. The order of antimalarial activity in vivo followed the capacity for a redox change of the iron(III)state which has important implications for the future rational design of 4- aminoquinoline antimalarials

Understanding Sensory Nerve Mechanotransduction through Localized Elastomeric Matrix Control

BACKGROUND: While neural systems are known to respond to chemical and electrical stimulation, the effect of mechanics on these highly sensitive cells is still not well understood. The ability to examine the effects of mechanics on these cells is limited by existing approaches, although their overall response is intimately tied to cell-matrix interactions. Here, we offer a novel method, which we used to investigate stretch-activated mechanotransduction on nerve terminals of sensory neurons through an elastomeric interface. METHODOLOGY/PRINCIPAL FINDINGS: To apply mechanical force on neurites, we cultured dorsal root ganglion neurons on an elastic substrate, polydimethylsiloxane (PDMS), coated with extracellular matrices (ECM). We then implemented a controlled indentation scheme using a glass pipette to mechanically stimulate individual neurites that were adjacent to the pipette. We used whole-cell patch clamping to record the stretch-activated action potentials on the soma of the single neurites to determine the mechanotransduction-based response. When we imposed specific mechanical force through the ECM, we noted a significant neuronal action potential response. Furthermore, because the mechanotransduction cascade is known to be directly affected by the cytoskeleton, we investigated the cell structure and its effects. When we disrupted microtubules and actin filaments with nocodozale or cytochalasin-D, respectively, the mechanically induced action potential was abrogated. In contrast, when using blockers of channels such as TRP, ASIC, and stretch-activated channels while mechanically stimulating the cells, we observed almost no change in action potential signalling when compared with mechanical activation of unmodified cells. CONCLUSIONS/SIGNIFICANCE: These results suggest that sensory nerve terminals have a specific mechanosensitive response that is related to cell architecture

Wanted dead or alive : high diversity of macroinvertebrates associated with living and ’dead’ Posidonia oceanica matte

The Mediterranean endemic seagrass Posidonia oceanica forms beds characterised by a dense leaf canopy and a thick root-rhizome ‘matte’. Death of P. oceanica shoots leads to exposure of the underlying matte, which can persist for many years, and is termed ‘dead’ matte. Traditionally, dead matte has been regarded as a degraded habitat. To test whether this assumption was true, the motile macroinvertebrates of adjacent living (with shoots) and dead (without shoots) matte of P. oceanica were sampled in four different plots located at the same depth (5–6 m) in Mellieha Bay, Malta (central Mediterranean). The total number of species and abundance were significantly higher (ANOVA; P<0.05 and P<0.01, respectively) in the dead matte than in living P. oceanica matte, despite the presence of the foliar canopy in the latter. Multivariate analysis (MDS) clearly showed two main groups of assemblages, corresponding to the two matte types. The amphipods Leptocheirus guttatus and Maera grossimana, and the polychaete Nereis rava contributed most to the dissimilarity between the two different matte types. Several unique properties of the dead matte contributing to the unexpected higher number of species and abundance of motile macroinvertebrates associated with this habitat are discussed. The findings have important implications for the conservation of bare P. oceanica matte, which has been generally viewed as a habitat of low ecological value.peer-reviewe

Purpurogallin-A heme binding component of oak galls

Recently, it has been shown that Purpurogallin (PPG), an orange benztropolone constituent of oak galls and its derivative, CU-CPT22, can compete with the binding of the specific lipoprotein ligand to toll-like receptors (TLRs), which are type I transmembrane proteins. These recognize pathogen-derived macromolecules that play a key role in the innate immune system. This system provides an attractive target for the treatment of various immune disorders. Notably, PPG also interacts with various metals and its mode of action against HIV in vitro may involve inhibition of metal containing integrases. In the current study, an optimised synthesis of PPG is presented together with its gas phase behaviour (probed by mass spectrometry) as well as its redox behaviour with porphyrins such as heme. This interaction may also explain its effects at metal containing integrases within HIV in vitro as well as its action during processing of iron complexes within Plasmodia. This compound could serve as a novel prototype for the synthesis of novel redox active antimalarials