Synthesis and characterization of triblock copolymers of methoxy poly(ethylene glycol) and poly(propylene fumarate)

Amphiphilic block copolymers were synthesized by transesterification of hydrophilic methoxy poly(ethylene glycol) (mPEG) and hydrophobic poly(propylene fumarate) (PPF) and characterized. Four block copolymers were synthesized with a 2:1 mPEG:PPF molar ratio and mPEGs of molecular weights 570, 800, 1960, and 5190 and PPF of molecular weight 1570 as determined by NMR. The copolymers synthesized with mPEG of molecular weights 570 and 800 had 1.9 and 1.8 mPEG blocks per copolymer, respectively, as measured by NMR, representing an ABA-type block copolymer. The number of mPEG blocks of the copolymer decreased with increasing mPEG block length to as low as 1.5 mPEG blocks for copolymer synthesized with mPEG of molecular weight 5190. At a concentration range of 5-25 wt % in phosphate-buffered saline, copolymers synthesized with mPEG molecular weights of 570 and 800 possessed lower critical solution temperatures (LCST) between 40 and 45 degrees C and between 55 and 60 degrees C, respectively. Aqueous solutions of copolymer synthesized with mPEG 570 and 800 also experienced thermoreversible gelation. The sol-gel transition temperature was dependent on the sodium chloride concentration as well as the mPEG block length. The copolymer synthesized from mPEG 570 had a transition temperature between 40 and 20 degrees C with salt concentrations between 1 and 10 wt %, while the sol-gel transition temperatures of the copolymer synthesized from mPEG molecular weight 800 were higher in the range 75-30 degrees C with salt concentrations between 1 and 15 wt %. These novel thermoreversible copolymers are the first biodegradable copolymers with unsaturated double bonds along their macromolecular chain that can undergo both physical and chemical gelation and hold great promise for drug delivery and tissue engineering applications.     

Solution‐Processed Hydrogen Molybdenum Bronzes as Highly Conductive Anode Interlayers in Efficient Organic Photovoltaics

Highly efficient and stable organic photovoltaic (OPV) cells are demonstrated by incorporating solution‐processed hydrogen molybdenum bronzes as anode interlayers. The bronzes are synthesized using a sol‐gel method with the critical step being the partial oxide reduction/hydrogenation using an alcohol‐based solvent. Their composition, stoichiometry, and electronic properties strongly correlate with the annealing process to which the films are subjected after spin coating. Hydrogen molybdenum bronzes with moderate degree of reduction are found to be highly advantageous when used as anode interlayers in OPVs, as they maintain a high work function similar to the fully stoichiometric metal oxide, whereas they exhibit a high density of occupied gap states, which are beneficial for charge transport. Enhanced short‐circuit current, open‐circuit voltage and, fill factor, relative to reference devices incorporating either PEDOT‐PSS or a solution processed stoichiometric molybdenum oxide, are obtained for a variety of bulk heterojunction mixtures based on different polymeric donors and fullerene acceptors. In particular, high power conversion efficiencies are obtained in devices that employed the s‐H_xMoO_2.75 as the hole extraction layer.     

Habitat associations and breeding success of yellowhammers on lowland farmland

1.  Yellowhammers began to decline on British lowland farmland in the late 1980s and losses are presently 10% per year. This study examined variation in the habitat selection and breeding success of yellowhammers, allowing an evaluation of whether Britain's yellowhammer decline might have been caused by recent changes in agriculture.
2.  Yellowhammer territories were associated with hedgerows, vegetated ditches and wide uncultivated grassy margins around fields. Pasture and silage leys were avoided. Nests were built among herbaceous vegetation in ditches or in the shrubby vegetation of hedgerows.
3.  Breeding started slightly earlier on organic farms than on intensively managed farms, but no measure of breeding success differed between farm types. Predation was the cause of most (64%) nest failures. A maximum of three breeding attempts (two successful) was observed per pair, with a mean clutch size of 3·3, a Mayfield nest success rate of 0·46, and 2·6 nestlings fledged per successful brood. These data, together with published estimates of adult yellowhammer survival and of post-fledging survival among other passerines, suggest that breeding productivity is too low to maintain a stable population.
4.  The removal of hedgerows or abandonment of hedge management, filling or clearing of ditches, intensification of grassland management and cropping or grazing right up to the field edge, are all likely to have adversely affected yellowhammers on lowland farmland in southern England. Policy reforms that redirect subsidy support to environmentally beneficial management of field margin habitats and retention of winter-feeding sites such as stubbles should assist in restoring populations of breeding yellowhammers on lowland farmland.
5.  Our data expand further the array of farmland bird species for which interactions between agricultural change and population change are increasingly understood.     

Intense basketball-simulated exercise induces muscle damage in men with elevated anterior compartment pressure

The purpose of the present investigation was to examine the levels of muscle soreness, muscle damage, and performance output in men with (S, n = 24) or without (A, n = 24) chronic compartment syndrome (CACS)-related symptoms after an intense 10-minute basketball-simulated exercise. Anterior compartment pressure (ICP), muscle soreness perception, creatine kinase (CK) and lactate dehydrogenase (LDH) activities, myoglobin (Mb) concentration, leg strength, and knee joint range of motion (KJRM) were measured at rest, immediately after exercise, and at 24, 48, 72 and 96 hours postexercise (ICP was also measured at 5, 15, and 30 minutes postexercise). ICP, muscle soreness, CK, LDH, and myoglobin increased (p < 0.05) immediately postexercise and during the next 4 days of recovery in both groups. However, S demonstrated a far more pronounced and prolonged (p < 0.05) response than A. Leg strength and KJRM declined (p < 0.05) in both groups, but S demonstrated a greater (p < 0.05) performance deterioration than A. The results of this study suggest that intense basketball-simulated exercise increases ICP, muscle soreness, and indices of muscle damage with a concomitant decrease of performance. Men with CACS-related symptoms and/or history appear more sensitive to muscle damage and soreness than asymptomatic men, probably due to a compromised blood flow to the muscle producing fluid shifts from vascular to interstitial space and further increasing compartment pressure and muscle cell disruption. Results of the present investigation provide evidence to support proper diagnosis, monitoring, care, and preventive measures for symptomatic individuals prior to participation in activities such as basketball.     

Role of Endothelial Progenitor Cells and Inflammatory Cytokines in Healing of Diabetic Foot Ulcers

Background

To evaluate changes in endothelial progenitor cells (EPCs) and cytokines in patients with diabetic foot ulceration (DFU) in association with wound healing.

Methods

We studied healthy subjects, diabetic patients not at risk of DFU, at risk of DFU and with active DFU. We prospectively followed the DFU patients over a 12-week period. We also investigated similar changes in diabetic rabbit and mouse models of wound healing.

Results

All EPC phenotypes except the kinase insert domain receptor (KDR)⁺CD133⁺ were reduced in the at risk and the DFU groups compared to the controls. There were no major EPC differences between the control and not at risk group, and between the at risk and DFU groups. Serum stromal-cell derived factor-1 (SDF-1) and stem cell factor (SCF) were increased in DFU patients. DFU patients who healed their ulcers had lower CD34⁺KDR⁺ count at visits 3 and 4, serum c-reactive protein (CRP) and granulocyte-macrophage colony-stimulating factor (GM-CSF) at visit 1, interleukin-1 (IL-1) at visits 1 and 4. EPCs tended to be higher in both diabetic animal models when compared to their non-diabetic counterparts both before and ten days after wounding.

Conclusions

Uncomplicated diabetes does not affect EPCs. EPCs are reduced in patients at risk or with DFU while complete wound healing is associated with CD34⁺KDR⁺ reduction, suggesting possible increased homing. Low baseline CRP, IL-1α and GM-CSF serum levels were associated with complete wound healing and may potentially serve as prognostic markers of DFU healing. No animal model alone is representative of the human condition, indicating the need for multiple experimental models.     

Emerging intra-articular drug delivery systems for the temporomandibular joint

Temporomandibular joint (TMJ) disorders are a heterogeneous group of diseases that cause progressive joint degeneration leading to chronic pain and reduced quality of life. Both effective pain reduction and restoration of TMJ function remain unmet challenges. Intra-articular injections of corticosteroids and hyaluronic acid are currently used to treat chronic pain, but these methods require multiple injections that increase the risk of iatrogenic joint damage and other complications. The small and emerging field of TMJ tissue engineering aims to reduce pain and disability through novel strategies that induce joint tissue regeneration. Development of methods for sustained, intra-articular release of growth factors and other pro-regenerative signals will be critical for the success of TMJ tissue engineering strategies. This review discusses methods of intra-articular drug delivery to the TMJ, as well as emerging injectable controlled release systems with potential to improve TMJ drug delivery, to encourage further research in the development of sustained release systems for both long-term pain management and to enhance tissue engineering strategies for TMJ regeneration.     

Evaluation of the fully automated Bactec MGIT 960 system for the susceptibility testing of Mycobacterium tuberculosis to first-line drugs: a multicenter study

The accuracy of the Bactec MGIT 960 system for susceptibility testing of 177 clinical isolates of Mycobacterium tuberculosis to first line drugs (isoniazid, rifampicin, ethambutol and streptomycin) was compared with the agar reference method. The sensitivity, the ability to detect resistance, of the MGIT system was 100%, while the specificity, the ability to detect susceptibility, ranged from 98.6% to 100% for all drugs tested.     

Changes in metalloproteinases in healthy normotensive patients with high-normal blood pressure

INTRODUCTION: High-normal blood pressure (HNBP) seems to be related to increased cardiovascular risk in healthy, normotensive subjects, while essential hypertension is associated with an increase in extracellular matrix content, especially fibrillar collagen type I. The aim of our study was to investigate whether collagen degradation is altered in healthy normotensives with HNBP, and whether this alteration could be related to disturbances in the matrix metalloproteinases plasma concentration, and to compare the findings to those of healthy normotensives with normal blood pressure (NBP) levels, matched for age, sex and BMI. METHODS: Twenty six (14 males, 12 females) healthy, normotensive patients with HNBP, mean age 52 +/- 5 yrs, and BMI 23 +/- 1.5 kg/m(2) (group A), and 24, healthy normotensive patients (13 males, 11 females) with NBP, mean age 53 +/- 6 yrs, and BMI 23.2 +/- 1.4 kg/m(2) (group B), were studied. The two groups were matched for age, sex and BMI. Plasma levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors (TIMP-1) and (TIMP-4) were determined by relevant ELISA in the study population. RESULTS: Plasma MMP-9 levels were significantly higher, while TIMP-1 and TIMP-4 levels were significantly lower in group A compared to group B, (MMP-9 579 +/- 147 versus 294 +/- 111 ng/mL, TIMP-1 178 +/- 45 versus 237 +/- 35 ng/mL p < 0.01, and TIMP-4 2.2 +/- 1.4 versus 4.4 +/- 2.1 p < 0.04 respectively). CONCLUSIONS: Our findings suggest that healthy normotensives with high-normal blood pressure have significantly increased MMP-9 and decreased TIMP-1 and TIMP-4 plasma levels compared to healthy normotensives with normal blood pressure. These findings need further investigation.     

Pepino mosaic virus triple gene block protein 1 (TGBp1) interacts with and increases tomato catalase 1 activity to enhance virus accumulation

Various plant factors are co‐opted by virus elements (RNA, proteins) and have been shown to act in pathways affecting virus accumulation and plant defence. Here, an interaction between Pepino mosaic virus (PepMV) triple gene block protein 1 (TGBp1; p26) and tomato catalase 1 (CAT1), a crucial enzyme in the decomposition of toxic hydrogen peroxide (H₂O₂), was identified using the yeast two‐hybrid assay, and confirmed via an in vitro pull‐down assay and bimolecular fluorescent complementation (BiFC) in planta. Each protein was independently localized within loci in the cytoplasm and nuclei, sites at which their interaction had been visualized by BiFC. Following PepMV inoculation, CAT mRNA and protein levels in leaves were unaltered at 0, 3 and 6 days (locally) and 8 days (systemically) post‐inoculation; however, leaf extracts from the last two time points contained increased CAT activity and lower H₂O₂ levels. Overexpression of PepMV p26 in vitro and in planta conferred the same effect, suggesting an additional involvement of TGBp1 in potexvirus pathogenesis. The accumulation of PepMV genomic and subgenomic RNAs and the expression of viral coat protein in noninoculated (systemic) leaves were reduced significantly in CAT‐silenced plants. It is postulated that, during PepMV infection, a p26–CAT1 interaction increases H₂O₂ scavenging, thus acting as a negative regulator of plant defence mechanisms to promote PepMV infections.