Thiolated Janus Silsesquioxane Tetrapod: New Precursors for Functional Materials.

Herein, we report synthetic strategies for the development of a bifunctional Janus T4 tetrapod (Janus ring), in which the orthogonal silsesquioxane and organic faces are independently functionalized. An all-cis T4 tetrasilanolate was functionalized to introduce thiol moieties on the silsesquioxane face and naphthyl groups on the organic face to introduce luminescent and self-organization properties. The stepwise synthesis conditions required to prepare such perfectly defined oligomers via a suite of well-defined intermediates and to avoid polymerization or reactions over all eight positions of the tetrapod are explored via 29Si, 13C and 1H NMR, FTIR and TOF-ESI mass spectroscopy. To the best of our knowledge, this is one of the few reports of Janus T4 tetrapods, with different functional groups located on both faces of the molecule, thus expanding the potential range of applications for these versatile precursors.

Mesoporous organosilicas with thiol functionalised pores: multifunctional dendrimers as sacrificial building block and template.

The synthesis of multifunctional poly(amidoamine) (PAMAM)-based dendrimers containing a cleavable disulfide linker within each arm of the dendrimer, together with condensable triethoxysilyl groups on the periphery of the dendrimer, is described. The dendrimers were mixed with 1,4-bis(triethoxysilyl)benzene and subsequently transformed into silsesquioxane gels or periodic mesoporous organosilicas (PMOs) to generate materials with dendrimers covalently embedded within the interior of the silsesquioxane networks. Subsequent treatment of the gels with dithiothreitol enabled the core of the dendrimers to be selectively cleaved at the disulfide site, thus generating thiol functions localised within the pores. The effect of different dendrimer generations on the reactivity of the pendant thiol functions was probed by impregnation with gold salts, which were reduced to obtain gold nanoparticles within the pore networks of the gels and PMOs. The gels yielded polydisperse gold nanoparticles (2 to 70 nm) with dimensions modulated by the generation of the dendrimer, together with well-defined gold/thiolate clusters with Au⋯S distances of 2.3 Å. Such clusters were also observed in the PMO system, together with monodispersed gold nanoparticles with diameters comparable to that of the organised pores in the PMO. The role of surface functionalisation in controlling the formation of gold clusters and/or nanoparticles is discussed.

Large Polyhedral Oligomeric Silsesquioxane Cages: The Isolation of Functionalized POSS with an Unprecedented Si18 O27 Core.

The synthesis of organo-functionalized polyhedral oligomeric silsesquioxanes (POSS, (R-SiO1.5 )n , Tn ) is an area of significant activity. To date, T14 is the largest such cage synthesized and isolated as a single isomer. Herein, we report an unprecedented, single-isomer styryl-functionalized T18 POSS. Unambiguously identified among nine possible isomers by multinuclear solution NMR (1 H, 13 C, and 29 Si), MALDI-MS, FTIR, and computational studies, this is the largest single-isomer functionalized Tn compound isolated to date. A ring-strain model was developed to correlate the 29 Si resonances with the number of 6-, 5-, and/or 4-Si-atom rings that each non-equivalent Si atom is part of. The model successfully predicts the speciation of non-equivalent Si atoms in other families of Tn compounds, demonstrating its general applicability for assigning 29 Si resonances to Si atoms in cage silsesquioxanes and providing a useful tool for predicting Si-atom environments.

Functionalised polyhedral oligomeric silsesquioxane with encapsulated fluoride - first observation of fluxional SiF interactions in POSS.

The synthesis of a styryl functionalised POSS incorporating an encapsulated fluoride ion within a (SiO1.5)8 cage (T8-F) is reported. It was characterised by single crystal XRD, MALDI-MS, FTIR, solution (29Si, 19F, 13C, 1H) and solid state (29Si, 19F) NMR. In the absence of 1H decoupling, the 29Si solution NMR spectrum exhibited a triplet of doublets. In contrast, 1H, 19F and 1H/19F double-decoupling resulted in two, three and one signal, respectively, being consistent with a single Si site whose 29Si NMR signal is modulated by both the proximal aromatic-ring protons and fluoride. The associated SiF coupling constant (2.5 Hz) is substantially lower than expected for a covalent Si-F bond and arises from a fluxional SiF covalent effect in which the F- interacts equivalently with all eight Si atoms. Additional variable temperature NMR studies demonstrated a threshold at -5 °C below which no SiF interactions are observed, and above which an increasing SiF covalent character occurs.

Sequential delivery of synergistic drugs by silica nanocarriers for enhanced tumour treatment.

Herein hybrid silica nanoparticles have been engineered to direct the sequential delivery of multiple chemotherapeutic drugs in response to external stimuli such as variations in pH. The nanocarriers consist of conventional MCM-41-type nanoparticles, which have been functionalised with an organic ligand (or stalk) grafted onto the external surface. The stalk is designed to "recognise" a complementary molecule, which serves as a "cap" to block the pores of the nanoparticles. First, camptothecin is introduced into the pores by diffusion prior to capping the pore apertures via molecular recognition. The cap, which is a derivative of 5-fluorouracil, serves as a second cytotoxic drug for synergistic chemotherapy. In vitro tests revealed that negligible release of the drugs occurred at pH 7.4, thus avoiding toxic side effects in the blood stream. In contrast, the stalk/cap complex is destabilised within the endolysosomal compartment (pH 5.5) of cancer cells, where release of the drugs was demonstrated. Furthermore, this environmentally responsive system exhibited a synergistic effect of the two drugs, where the pH-triggered release of the cytotoxic cap followed by diffusion-controlled release of the drug cargo within the pores led to essentially complete elimination of breast cancer cells.

Infrared and Raman spectroscopy of non-conventional hydrogen bonding between N,N'-disubstituted urea and thiourea groups: a combined experimental and theoretical investigation.

The variety of H bond (HB) interactions is a source of inspiration for bottom-up molecular engineering through self-aggregation. Non-conventional intermolecular HBs between N,N'-disubstituted urea and thiourea are studied in detail by vibrational spectroscopies and ab initio calculations. Raman and IR mode assignments are given. We show that it is possible to study selectively the different intermolecular bifurcated intra- and inter-dimer HBs with the two types of HB acceptors. Through the ab initio calculation, the thioamide I mode, a specific marker of N-HS[double bond, length as m-dash]C HB interactions, is unambiguously identified.

The discrepancy between patient expectations and actual outcome reduces at the first 6 months following total knee replacement surgery.

PURPOSE: Patients undergoing total knee arthroplasty often have unfulfilled expectations from the surgery that can lead to dissatisfaction. This study aimed to examine the discrepancy between patients' expectations and actual functional abilities prior to undergoing knee replacement surgery, and at 6 and 12 months following the surgery. METHODS: A survey was undertaken of patients before, and 6 and 12 months post-surgery. The survey included the Knee Surgery Perception Questionnaire (KSPQ) to assess patients' current perception of their level of function and pain, their desired outcomes, and the discrepancy between the two. Pain, function and quality of life were also assessed. Repeated measure ANOVAs were used to assess differences between pre- and post-surgery. RESULTS: A total of 176 patients were surveyed. Significant differences in the KSPQ discrepancy scores (subscale and total scores) were demonstrated between the three assessment point times (p < 0.01). Paired t tests identified significant differences between the pre-surgery and 6-month KSPQ discrepancy scores, (p < 0.01) indicative of substantial improvement in physical function and slight reduction in expectations. Overall significant improvement (p < 0.01) was reported over time across all measures: physical function, pain and stiffness and quality of life. CONCLUSION: The discrepancy between patients' current abilities and their expectation changes following surgery, especially in the first 6 months post-surgery. Patients' goals might change as their function and pain improve post-surgery. Combining education programmes and discussion with the treating orthopaedic surgeons pre-operatively is important for the development of realistic, achievable expectations. LEVEL OF EVIDENCE: III.

Large-Pore Periodic Mesoporous Organosilicas as Advanced Bactericide Platforms.

Despite the versatility of periodic mesoporous organosilicas (PMOs), the bactericide capacity of these hybrid platforms has seldom been explored. Herein, we describe the synthesis of large-pore phenylene-bridged PMOs, mesostructured by polyion complex (PIC) micelles (PICPMOs) incorporating an antibiotic, neomycin B. A key feature of this approach is that the bioactive molecules are directly encapsulated within the PICPMOs during their formation. The engineered PICPMOs exhibit a well-ordered hexagonal mesophase with a molecular-scale crystallinity and large mesopores (8 nm), which facilitates pH-triggered delivery of the drug. The results obtained with a pathogenic Escherichia coli strain clearly demonstrate the potential of such PICPMOs for antibacterial applications.

Pre-operative predictors of post-operative falls in people undergoing total hip and knee replacement surgery: a prospective study.

INTRODUCTION: Pain and disability often persist following hip (THR) and knee replacement (TKR) surgery predisposing patients to increased risk of falling. This study identified pre-operative predictors for post-operative falls in TKR and THR patients, and the incidence and circumstances of falls in the 12 months post-surgery. MATERIALS AND METHODS: A survey was undertaken of patients before THR and TKR, and was repeated 12 months post-operation. The survey included (1) medical history and medications usage, (2) pain and function, (3) health-related and physical activity and (4) fear of falls and history of falls questionnaires. Patients were classified as 'fallers' (≥1 fall) or 'non-fallers' based on prospectively documented falls in the 12 months post-surgery. Binary logistic regression was conducted to identify independent pre-operative predictors of incident falls status. RESULTS: Eighty-two of the 243 participants (33.7%) reported ≥1 fall in the 12 months post-operatively [60 (34.1%) patients following TKR and 22 (32.8%) following THR]. The logistic regression model was statistically significant, χ 2 = 24.731, p < 0.001, the model explaining 22% of the variance in falls, and correctly classifying 73.7% of cases as fallers or non-fallers. Reduced SF-36v2 general health sub-scale, increased planned physical activity and previous falls in the preceding year were predictors of falls. Those reporting ≥1 fall pre-operatively were three times more likely to fall post-operatively. CONCLUSION: People awaiting hip or knee joint replacement surgery might present with complex conditions that predispose them to greater risk of falling post-operation. Review of general health and history of falling is recommended pre-operatively to identify patients at risk.

Skeletal muscle vitamin D in patients with end stage osteoarthritis of the knee.

Muscle function is often impaired in patients with knee osteoarthritis (OA), with reduced strength and increased pain. The role of vitamin D and the vitamin D-endocrine pathway in muscle health has recently been placed in the spotlight, with various groups reporting positive effects on muscle development, function and health. Recently, it has been shown that uptake into muscle of the specialized vitamin D binding protein (DBP) is dependent on the endocytic receptor, megalin. Here we analyse circulating vitamin D, and muscle DBP, megalin and the cognate vitamin D receptor (VDR) in patients with knee OA and compare them to asymptomatic controls. Muscle and blood samples were collected from 19 patients with end-stage OA of the knee and 10 age-matched controls. Muscle biopsies from the OA group were performed during knee replacement surgery and a needle biopsy was used on control volunteers. Immunoblots performed with specific antibodies were used to detect the presence of DBP, megalin, VDR (using the specific D-6 antibody) and albumin in the muscle biopsies. Results were correlated with FoxO1, a key regulator of the ubiquitin-proteasome degradation pathway in muscle. There were no differences in circulating levels of 25 (OH) vitamin D3 between the groups, and no subjects were vitamin D deficient. We found increased VDR, DBP and albumin protein in the muscle from patients with OA compared to controls, with no change in muscle megalin expression. Furthermore, DBP levels in the muscle correlated with FoxO1, suggesting an association between muscle protein breakdown and the activation of the vitamin D-endocrine pathway in muscle surrounding an OA affected joint. We show, for the first time, that the factors involved in the vitamin D-endocrine-pathway are present at higher levels in muscles from OA patients compared to asymptomatic controls. This is despite no differences in circulating 25 (OH) vitamin D levels between the groups. These findings indicate the activation of vitamin D pathway in these muscles that may provide a beneficial compensatory stimulation of the repair process in muscles that are subject to inflammatory and proteolytic processes.

Evaporation-induced self-structuring of organised silica nanohybrid films through cooperative physical and chemical interactions.

In this work, we develop the concept of evaporation-induced self-structuring as a novel approach for producing organised films by exploiting cooperative physical and chemical interactions under far-from-equilibrium conditions (spin-coating), using sol-gel precursors with multiple functional groups. Thin films of self-structured silsesquioxane nanohybrids have been deposited by spin coating through the sol-gel hydrolysis and condensation of a bridged organosilane bearing self-assembling urea groups. The resulting nanostructure, investigated by FTIR, AFM and SEM, is shown to be highly dependent on the catalyst used (nucleophilic or acidic), and can be further modulated by varying the spinning rate. FTIR studies revealed the presence of highly organised structures under acidic catalysis due to strong hydrogen bonding between urea groups and hydrophobic interactions between long alkylene chains. The preferential orientation of the urea cross-links parallel to the substrate is shown using polarized FTIR experiments.

Development and validation of a questionnaire assessing discrepancy between patients' pre-surgery expectations and abilities and post-surgical outcomes following knee replacement surgery.

PURPOSE: The discrepancy between patient-desired outcomes and achievable functional outcomes is a source of patient dissatisfaction. This paper reports development and validation of a questionnaire to assess this discrepancy in patients undergoing knee replacement surgery. METHODS: The initial questionnaire (Knee Surgery Perception Questionnaire, KSPQ) comprised two parts. Part A, assessed patients' perception of their current level of function and pain, and Part B, assessed patients' desired outcomes of the surgery. Validation was carried out for Part A and then applied to Part B using a one-factor congeneric model and was tested in 185 patients preceding surgery. A discrepancy score between patients' expectations and desired outcome (Part B) and their perception of current function (Part A) was also calculated. Pearson correlations were used between the KSPQ total score and subscales and other knee-specific questionnaires to determine construct validity. RESULTS: The final best set of models included four items for each subscale with a Chi-square value of 7.3 (n.s). The subscales and the total KSPQ showed significant strong to moderate correlations with knee-specific questionnaires. The discrepancy score in each subscale and the overall score showed relatively large discrepancy between patients' expectations and their perception of current function; with higher discrepancy score reported for pain and walking. CONCLUSION: The KSPQ is a valid questionnaire to assess patients' expected and desired outcomes of knee replacement surgery and their perception of their current abilities and function, and discrepancy between these. The KSPQ now requires further investigation at different stages of recovery following surgery. LEVEL OF EVIDENCE: III.

Eu³âº-based bridged silsesquioxanes for transparent luminescent solar concentrators.

The sol-gel preparation of a bridged silsesquioxane containing europium(III) salts and 2-thenoyltrifluoroacetone has been achieved from a new ethane tetracarboxamide-based organosilane. Free-standing films with thicknesses up to 440 µm and maximum absolute quantum yield (q) of 0.34 ± 0.03 (excitation at 320 nm) were prepared by the drop cast method, while thin films (∼200-400 nm) spin-coated on glass substrates led to highly luminescent coatings with q = 0.60 ± 0.02 (excitation at 345 nm). The thin films were tested as planar luminescent solar concentrators and the optimized device displays an optical conversion efficiency of 12.3% in the absorbing spectral region of the active layer (300-380 nm).

The effects of osteoarthritis and age on skeletal muscle strength, Na+-K+-ATPase content, gene and isoform expression.

Knee osteoarthritis (OA) is a debilitating disorder prevalent in older populations that is accompanied by declines in muscle mass, strength, and physical activity. In skeletal muscle, the Na(+)-K(+) pump (NKA) is pivotal in ion homeostasis and excitability and is modulated by disuse and exercise training. This study examined the effects of OA and aging on muscle NKA in 36 older adults (range 55-81 yr), including 19 with OA (69.9 ± 6.5 yr, mean ± SD) and 17 asymptomatic controls (CON, 66.8 ± 6.4 yr). Participants completed knee extensor strength testing and a physical activity questionnaire. A vastus lateralis muscle biopsy was analyzed for NKA content ([(3)H]ouabain binding sites), α1-3- and ß1-3-isoform protein abundance (immunoblotting), and mRNA (real-time RT-PCR). The association between age and NKA content was investigated within the OA and CON groups and in pooled data. The NKA content was also contrasted between subgroups below and above the median age of 68.5 yr. OA had lower strength (-40.8%, P = 0.005), but higher NKA α2- (∼34%, P = 0.006) and α3-protein (100%, P = 0.016) abundance than CON and performed more incidental physical activity (P = 0.035). No differences were found between groups for NKA content, abundance of other NKA isoforms, or gene expression. There was a negative correlation between age and NKA content within OA (r = -0.63, P = 0.03) and with both groups combined (r = -0.47, P = 0.038). The NKA content was 25.5% lower in the older (69-81 yr) than in the younger (55-68 yr) subgroup. Hence older age, but not knee OA, was related to lowered muscle NKA content in older adults.

Relationship between foot function and medial knee joint loading in people with medial compartment knee osteoarthritis.

BACKGROUND: Dynamic joint loading, particularly the external knee adduction moment (KAM), is an important surrogate measure for the medio-lateral distribution of force across the knee joint in people with knee osteoarthritis (OA). Foot motion may alter the load on the medial tibiofemoral joint and hence affect the KAM. Therefore, this study aimed to investigate the relationship between tibia, rearfoot and forefoot motion in the frontal and transverse planes and the KAM in people with medial compartment knee OA. METHOD: Motion of the knee, tibia, rearfoot and forefoot and knee moments were evaluated in 32 patients with clinically and radiographically-confirmed OA, predominantly in the medial compartment. Pearson's correlation coefficient was used to investigate the association between peak values of tibia, rearfoot and forefoot motion in the frontal and transverse planes and 1st peak KAM, 2nd peak KAM, and the knee adduction angular impulse (KAAI). RESULTS: Lateral tilt of the tibia was significantly associated with increased 1st peak KAM (r = 0.60, p < 0.001), 2nd peak KAM (r = 0.67, p = 0.001) and KAAI (r = 0.82, p = 0.001). Increased peak rearfoot eversion was significantly correlated with decreased 2nd peak KAM (r = 0.59, p < 0.001) and KAAI (r = 0.50, p = 0.004). Decreased rearfoot internal rotation was significantly associated with increased 2nd peak KAM (r = -0.44, p = 0.01) and KAAI (r = -0.38, p = 0.02), while decreased rearfoot internal rotation relative to the tibia was significantly associated with increased 2nd peak KAM (r = 0.43, p = 0.01). Significant negative correlations were found between peak forefoot eversion relative to the rearfoot and 2nd peak KAM (r = -0.53, p = 0.002) and KAAI (r = -0.51, p = 0.003) and between peak forefoot inversion and 2nd peak KAM (r = -0.54, p = 0.001) and KAAI (r = -0.48, p = 0.005). CONCLUSION: Increased rearfoot eversion, rearfoot internal rotation and forefoot inversion are associated with reduced knee adduction moments during the stance phase of gait, suggesting that medial knee joint loading is reduced in people with OA who walk with greater foot pronation. These findings have implications for the design of load-modifying interventions in people with knee OA.

Self-assembly of bridged silsesquioxanes: modulating structural evolution via cooperative covalent and noncovalent interactions.

The self-assembly of a bis-urea phenylene-bridged silsesquioxane precursor during sol-gel synthesis has been investigated by in situ infrared spectroscopy, optical microscopy, and light scattering. In particular, the evolution of the system as a function of processing time was correlated with covalent interactions associated with increasing polycondensation and noncovalent interactions such as hydrogen bonding. A comprehensive mechanism based on the hydrolysis of the phenylene-bridged organosilane precursor prior to the crystallization of the corresponding bridged silsesquioxane via H-bonding and subsequent irreversible polycondensation is proposed.

Lower limb biomechanics in individuals with knee osteoarthritis before and after total knee arthroplasty surgery.

We investigated the biomechanical changes that occur in the lower limb following total knee arthroplasty (TKA). Lower limb joint kinematics and kinetics were evaluated in 32 patients before and 12 months following TKA and 28 age-matched controls. Analysis of variance with Bonferroni-adjusted post-hoc tests showed no significant changes in knee joint kinematics and kinetics following TKA despite significant improvements in pain and function. Significant increases in peak ankle plantarflexion and dorsiflexion moments and ankle power generation were observed which may be a compensatory response to impaired knee function to allow sufficient power generation for propulsion. Differences in knee gait parameters may arise as a result of the presence of osteoarthritis and mechanical changes associated with TKA as well as retention of the pre-surgery gait pattern.

Foot kinematics in people with medial compartment knee osteoarthritis.

OBJECTIVES: Foot orthoses are commonly used in the management of knee OA, although the relationship between foot function and knee OA is still unclear. The purpose of the study was to examine foot function during walking in people with and without medial compartment knee OA. METHODS: Motion of the tibia, rearfoot and forefoot in 32 patients with medial compartment knee OA and 28 age-matched control subjects was investigated. Multivariate analysis was used to compare the groups. RESULTS: The knee OA group contacted the ground with a more everted rearfoot, demonstrated greater peak rearfoot eversion and exhibited reduced rearfoot frontal plane range of motion and reduced rearfoot peak inversion. The tibia was more internally rotated and laterally tilted throughout the gait cycle, with reduced peak external rotation. CONCLUSION: People with medial compartment knee OA exhibit altered foot kinematics during gait that are indicative of a less mobile, more everted foot type. The presence and degree of tibial malalignment and the available rearfoot range of motion during walking may affect individual responses to load-altering interventions, such as foot orthoses and footwear modifications. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, www.anzctr.org.au/, ACTRN12608000116325.

Dynamic foot function changes following total knee replacement surgery.

BACKGROUND: Individuals with knee osteoarthritis (OA) have flatter/more pronated feet than those without OA, but it is unclear whether altered foot posture and function are a cause or consequence of knee OA. The purpose of this study was to examine whether changes in foot posture and function occur after realignment of the knee following total knee replacement (TKR). MATERIALS AND METHODS: Nineteen patients with predominantly medial compartment knee OA were tested prior to and 12 months after TKR. The Foot Posture Index (FPI) and Arch Index (AI) were measured as well as motion of the tibia, rearfoot and forefoot using a 3D motion analysis system incorporating a multisegment foot model. RESULTS: There were no significant changes in FPI or AI following TKR, however gait analysis revealed significant increases in tibial external rotation (-18.7 ± 7.0° vs -22.5 ± 8.7°, p=0.002), tibial transverse plane range of motion (-9.1 ± 4.6° vs -11.4 ± 6.1°, p=0.0028) and rearfoot range of motion in the frontal plane (8.6 ± 2.6° vs 10.4 ± 2.7°, p=0.002), and a decrease in rearfoot transverse plane range of motion (8.7 ± 5.3° vs 5.9 ± 4.1°, p=0.038) following the procedure. CONCLUSIONS: TKR produces no change in static foot posture, but results in significant changes in rearfoot kinematics during gait. These findings suggest that rearfoot motion compensates for changes in the alignment of the knee, highlighting the ability of the foot to accommodate for proximal skeletal malalignment.

Swing limb mechanics and minimum toe clearance in people with knee osteoarthritis.

OBJECTIVE: Knee osteoarthritis (OA) has been shown to be a risk factor for falls. Reductions in foot clearance during the swing phase of walking can cause a trip and potentially lead to a fall. This study examined the swing phase mechanics of people with and without knee OA during walking. DESIGN: Minimum toe clearance (MTC) height, joint angles at the time of MTC and the influence of the angular changes of the hip, knee and ankle of the swing leg on foot clearance using sensitivity analysis were investigated in 50 knee OA participants and 28 age-matched asymptomatic controls. RESULTS: Although both groups had a similar MTC height (controls: 12.8±6.7 mm, knee OA: 13.4±7.0 mm), the knee OA group used a different strategy to achieve the same foot clearance, as evidenced by greater knee flexion (52.5±5.3° vs 49.4±4.8°, p=0.007), greater hip abduction (-3.6±3.3° vs -1.8±3.3°, p=0.03) and less ankle adduction (2.8±1.9° vs 4.2±2.1°, p=0.01). CONCLUSION: MTC height was comparable between the groups, however a different swing phase mechanism was used by the knee OA. Although adequate MTC is an important component of safe locomotion, it does not appear to be impaired in people with knee OA. Other factors, such as inadequate responses to postural perturbation, may be responsible for falls in this group.