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Previous research from our labs demonstrated the synthesis of polymerized simvastatin by ring-opening polymerization and slow degradation with controlled release of simvastatin in ...vitro. The objective of the present study was to evaluate the degradation and intramembranous bone-forming potential of simvastatin-containing polyprodrugs in vivo using a rat calvarial onlay model. Poly(ethylene glycol)-block-poly(simvastatin) and poly(ethylene glycol)-block-poly(simvastatin)-ran-poly(glycolide) were compared with simvastatin conventionally encapsulated in poly(lactic-co-glycolic acid) (PLGA) and pure PLGA. The rate of degradation was higher for PLGA with and without simvastatin relative to the simvastatin polyprodrugs. Significant new bone growth at the circumference of poly(ethylene glycol)-block-poly(simvastatin) disks was observed beginning at 4 weeks, whereas severe bone resorption (4 weeks) and bone loss (8 weeks) were observed for PLGA loaded with simvastatin. No significant systemic effects were observed for serum total cholesterol and body weight. Increased expression of osteogenic (BMP-2, Runx2, and ALP), angiogenic (VEGF), and inflammatory cytokines (IL-6 and NF-ĸB) genes was seen with all polymers at the end of 8 weeks. Poly(ethylene glycol)-block-poly(simvastatin), with slow degradation and drug release, controlled inflammation, and significant osteogenic effect, is a candidate for use in bone regeneration applications.
Traditional drug delivery systems, e.g., drug encapsulated in poly(lactic-co-glycolic acid) (PLGA), are typically passive and have limited drug payload. As an alternative, we polymerized the drug simvastatin, which has multiple physiological effects, into macromolecules (“polysimvastatin”) via ring-opening polymerization. We previously demonstrated that the rate of degradation and drug (simvastatin) release can be adjusted by copolymerizing it with other monomers. The present results demonstrate significant new bone growth around polysimvastatin, whereas severe bone loss occurred for PLGA loaded with simvastatin. This degradable biomaterial with biofunctionality integrated into the polymeric backbone is a useful candidate for bone regeneration applications.
Elastic electron-proton scattering (e-p) and the spectroscopy of hydrogen atoms are the two methods traditionally used to determine the proton charge radius, r
. In 2010, a new method using muonic ...hydrogen atoms
found a substantial discrepancy compared with previous results
, which became known as the 'proton radius puzzle'. Despite experimental and theoretical efforts, the puzzle remains unresolved. In fact, there is a discrepancy between the two most recent spectroscopic measurements conducted on ordinary hydrogen
. Here we report on the proton charge radius experiment at Jefferson Laboratory (PRad), a high-precision e-p experiment that was established after the discrepancy was identified. We used a magnetic-spectrometer-free method along with a windowless hydrogen gas target, which overcame several limitations of previous e-p experiments and enabled measurements at very small forward-scattering angles. Our result, r
= 0.831 ± 0.007
± 0.012
femtometres, is smaller than the most recent high-precision e-p measurement
and 2.7 standard deviations smaller than the average of all e-p experimental results
. The smaller r
we have now measured supports the value found by two previous muonic hydrogen experiments
. In addition, our finding agrees with the revised value (announced in 2019) for the Rydberg constant
-one of the most accurately evaluated fundamental constants in physics.
The facile solvent-free synthesis of several known metal thiophosphates was accomplished by a chemical exchange reaction between anhydrous metal chlorides and elemental phosphorus with sulfur, or ...combinations of phosphorus with molecular P2S5 at moderate 500 °C temperatures. The crystalline products obtained from this synthetic approach include MPS3 (M = Fe, Co, Ni) and Cu3PS4. The successful reactions benefit from thermochemically favorable PCl3 elimination. This solvent-free route performed at moderate temperatures leads to mixed anion products with complex heteroatomic anions, such as P2S64−. The MPS3 phases are thermally metastable relative to the thermodynamically preferred separate MPx/ MSy and more metal-rich MPxSy phases. The micrometer-sized M-P-S products exhibit room-temperature optical and magnetic properties consistent with isolated metal ion structural arrangements and semiconducting band gaps. The MPS3 materials were examined as electrocatalysts in hydrogen evolution reactions (HER) under acidic conditions. In terms of HER activity at lower applied potentials, the MPS3 materials show the trend of Co > Ni >> Fe. Extended time constant potential HER experiments show reasonable HER stability of ionic and semiconducting MPS3 (M = Co, Ni) structures under acidic reducing conditions.
Endoscopic treatment for pilonidal disease was initially described by Meinero in 2013. This minimally invasive technique has both technical and aesthetic advantages. The diagnostic application helps ...identify the anatomy of the pilonidal disease and the operative phase ablates and cleans the infected cavity. Our aim was to study the short-term outcomes of endoscopic treatment for pilonidal disease and to evaluate complications and recurrence rates.
A prospectively maintained database of all consecutive patients who underwent endoscopic treatment for pilonidal disease by a single surgeon in a district general hospital from 1 November 2014 to 31 March 2018 was analysed. Follow-up was available until 30 September 2018.
A total of 74 patients (56 men) underwent endoscopic treatment for pilonidal disease. The median age was 21 years (range 16-62 years). All patients underwent the procedure as daycase procedures, seven under local anaesthesia. There were no immediate postoperative complications and no return to theatre or readmission within 90 days. On a median follow-up of 52 weeks (range 2-114 weeks), 57 patients healed completely and 8 lost to follow-up. We achieved primary healing rates of 67% (44/66) and delayed healing rate of 77% (51/66).
Endoscopic treatment for pilonidal disease is a safe and effective minimally invasive technique that should be considered as first-line treatment in selected cases of pilonidal sinus disease, thereby reducing morbidity related to conventional procedures.
Here we report the synthesis and genetic encoding of the lysine post translational modifications, β-hydroxybutyryl-lysine, isobutyryl-lysine and isovaleryl-lysine. The ability to obtain a homogenous ...protein samples with site-specific incorporation of these acylated lysine residues can serve as a powerful tool to study the biological role of lysine post translational modifications.
Skeletal dysplasias are a diverse group of rare disorders in the chondro-osseous tissue that can have a significant impact on patient's functionality. The worldwide prevalence of skeletal dysplasias ...at birth is approximately 1:5000 births. To date, disease burden and trends of skeletal dysplasias in the Sri Lankan population have not been described in any epidemiological study. Our aim was to evaluate the burden and the current trends in hospital admissions for skeletal dysplasias in the Sri Lankan population. A retrospective evaluation of hospital admissions for skeletal dysplasia during 2017-2020 was performed using population-based data from the eIMMR database which covers government hospitals in the entire country. The trends in hospital admissions for skeletal dysplasias by calendar year, age, and types of skeletal dysplasia were described using appropriate summary statistics. Respective crude admission rates of skeletal dysplasias in the years 2017, 2018, 2019 and 2020 were 5.2, 8.1, 8.0, and 6.5 per million population. A female predominance (1.4:1) was noted during the studied period. Of all reported cases the majority (n = 268; 44.2%) were children less than 4 years. Each year, 0-4 years age group represented 40-47% of the total hospital admissions. More than half of the cases were reported from Colombo (28.1%) and Kandy (25.4%) districts combined. 60% of cases were diagnosed as osteogenesis imperfecta (OI). Rising trends were observed in the hospital admissions for osteogenesis imperfecta, achondroplasia and osteopetrosis, while other skeletal dysplasia types collectively showed a relatively stable trend. This preliminary study revealed a female predominance of skeletal dysplasias and a relatively high admission rate of osteogenesis imperfecta in the Sri Lankan population. A distinct trend was not visible in the studied years probably due to the impact on hospital services due to COVID- Pandemic. Future research on the healthcare burden on families affected by skeletal dysplasia is required to better understand the overall cost of care and identify therapies that reduce admission rates. This study highlights the value of analysing population-based data on rare diseases to improve healthcare in low-resource countries.
Empirical observation and quantum chemical explanation of a likely common but “overlooked” outcome of the donor–acceptor (D–A) approach to organic electronic materials are reported. The frontier ...molecular orbitals (FMOs) of D–A copolymers prepared from the amidated Pechmann dye unit (APD) are dictated primarily by this “acceptor,” largely because its HOMO–LUMO gap falls within the gaps of common “donor” units. D–A copolymers with common benzodithiophene and cyclopentadithiophene units as “donors” are presented, giving examples having similar optical properties regardless of backbone planarity and solid‐state packing motif, along with calculations extending to several other common donor monomers to indicate generality. According to quantum‐chemical studies, APD‐localized FMOs form the transition to the lowest excited state, and higher lying charge‐transfer (CT) states. Other existing examples of this FMO situation are likely, but with (opto)electronic properties attributed to lack of conjugation due to, e.g., polymer backbone twisting.
The optical properties of “donor–acceptor” copolymers of an amidated Pechman dye (APD) are dictated almost completely by the APD unit alone. Quantum chemical studies reveal the cause to be the location of APD's HOMO–LUMO gap within those of common donors, giving examples of the fifth of five general outcomes of the donor–acceptor approach.
The Spin Asymmetries of the Nucleon Experiment measured two double spin asymmetries using a polarized proton target and polarized electron beam at two beam energies, 4.7 and 5.9 GeV. A ...large-acceptance open-configuration detector package identified scattered electrons at 40° and covered a wide range in Bjorken x (0.3<x<0.8). Proportional to an average color Lorentz force, the twist-3 matrix element, dover ˜_{2}^{p}, was extracted from the measured asymmetries at Q^{2} values ranging from 2.0 to 6.0 GeV^{2}. The data display the opposite sign compared to most quark models, including the lattice QCD result, and an unexpected scale dependence. Furthermore, when combined with the neutron data in the same Q^{2} range the results suggest a flavor independent average color Lorentz force.
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