Changes of early post-traumatic osteoarthritis in an ovine model of simulated ACL reconstruction are associated with transient acute post-injury synovial inflammation and tissue catabolism

SummaryThe study described here tested the hypothesis that early intra-articular inflammation is associated with the development of post-traumatic osteoarthritis (PTOA) in a sheep model. We extended previously published work in which we investigated joint gross morphology and synovial mRNA expression of inflammatory and catabolic molecules 2 weeks after anatomic Anterior cruciate ligament (ACL) autograft reconstructive surgery (ACL-R). The same variables have been analyzed at 20 weeks post surgery together with new experimental variables at both time points. Animals were sacrificed at 20 weeks post ACL-R surgery and their joints graded for signs of PTOA. Synovial samples were harvested for histological grading plus mRNA and protein analysis for a panel of inflammatory and catabolic molecules. The mRNA expression levels for this panel plus connective tissue matrix turnover molecules were also investigated in cartilage samples. Results of gross morphological assessments at 20 weeks post surgery showed some changes consistent with early OA, but indicated little progression of damage from the 2 week time point. While significant alterations in mRNA levels for synovial inflammatory and catabolic molecules were detected at 2 weeks, values had normalized by 20 weeks. Similarly, all mRNA expression levels for inflammatory and catabolic molecules in articular cartilage had returned to normal levels by 20 weeks post ACL-R surgery. We conclude that synovial inflammatory processes are initiated very early after ACL-R surgery and may instigate events that lead to the gross cartilage and joint abnormalities observed as early as 2 weeks. However, the absence of sustained inflammation and joint instability may prevent OA progression

Singular potentials and annihilation

We discuss the regularization of attractive singular potentials $-\alpha _{s}/r^{s}$, $s\geq 2$ by infinitesimal imaginary addition to interaction constant $\alpha_{s}=\alpha_{s}\pm i0$. Such a procedure enables unique definition of scattering observables and is equal to an absorption (creation) of particles in the origin. It is shown, that suggested regularization is an analytical continuation of the scattering amplitudes of repulsive singular potential in interaction constant $\alpha_{s}$. The nearthreshold properties of regularized in a mentioned way singular potential are examined. We obtain expressions for the scattering lengths, which turn to be complex even for infinitesimal imaginary part of interaction constant. The problem of perturbation of nearthreshold states of regular potential by a singular one is treated, the expressions for level shifts and widths are obtained. We show, that the physical sense of suggested regularization is that the scattering observables are insensitive to any details of the short range modification of singular potential, if there exists sufficiently strong inelastic short range interaction. In this case the scattering observables are determined by solutions of Schrodinger equation with regularized potential $-(\alpha_{s}\pm i0)/r^{s}$. We point out that the developed formalism can be applied for the description of systems with short range annihilation, in particular low energy nucleon-antinucleon scattering.Comment: 10 page

Correlations in the Sine-Gordon Model with Finite Soliton Density

We study the sine-Gordon (SG) model at finite densities of the topological charge and small SG interaction constant, related to the one-dimensional Hubbard model near half-filling. Using the modified WKB approach, we find that the spectrum of the Gaussian fluctuations around the classical solution reproduces the results of the Bethe ansatz studies. The modification of the collective coordinate method allows us to write down the action, free from infra-red divergencies. The behaviour of the density-type correlation functions is non-trivial and we demonstrate the existence of leading and sub-leading asymptotes. A consistent definition of the charge-raising operator is discussed. The superconducting-type correlations are shown to decrease slowly at small soliton densities, while the spectral weight of right (left) moving fermions is spread over neighboring "4k_F" harmonics.Comment: 12 pages, 3 eps figures, REVTEX; a discussion of fermions is adde

Electronic Doping and Enhancement of n‐Channel Polycrystalline OFET Performance through Gate Oxide Modifications with Aminosilanes

Self-assembled monolayers (SAMs) are widely employed in organic field-effect transistors to modify the surface energy, surface roughness, film growth kinetics, and electrical surface potential of the gate oxide to control the device's operating voltage. In this study, amino-functionalized SAM molecules are compared to pure alkylsilane SAMS in terms of their impact on the electrical properties of organic field-effect transistors, using the n-type polycrystalline small molecule semiconductor material N,N′-dioctyl-3,4,9,10-perylenedicarboximide (PTCDI-C8). In order to understand the electronic impact of the amino groups, the effect of both the number of amino-containing functional groups and the SAM molecular length are systematically studied. Though amino-functionalized SAM materials have been studied previously, this study is, for the first time, able to shed light on the nature of the doping effect that occurs when the gate oxide is treated with polar aminosilane materials. By a comprehensive theoretical study of the interface on the molecular level, it is shown that the observed shift in the threshold voltage is caused by free charges, which are attracted to the PTCDI-C8 and are stabilized there by protonated aminosilanes. This attraction and the voltage shift can be systematically tuned by varying the length of the neutral terminal chain of the aminosilane. © 2021 The Authors. Advanced Materials Interfaces published by Wiley-VCH Gmb

Evidence that the TRH-like peptide pyroglutamyl-glutamyl-prolineamide in human serum may not be secreted by the pituitary gland

Recent studies have revealed that TRH-like immunoreactivity (TRH-LI) in human serum is predominantly pGlu-Glu-ProNH2 (< EEP-NH2), a peptide previously found in, among others tissues, the pituitary gland of various mammalian species. In the rat pituitary, < EEP-NH2 is present in gonadotrophs and its pituitary content is regulated by gonadal steroids and gonadotrophin-releasing hormone (GnRH). Hence, we reasoned that < EEP-NH2 in human serum may also arise, at least in part, from the pituitary, and that its secretion may correlate with that of gonadotrophins. Therefore, blood was simultaneously sampled from both inferior petrosal sinuses, which are major sites of the venous drainage of the pituitary gland, and a peripheral vein from seven patients with suspected adrenocorticotrophin-secreting pituitary tumours. In addition, in six postmenopausal and six cyclic women, peripheral vein blood was collected at 10-min intervals for 6 h, then a standard 100 micrograms GnRH test was performed. In the sera, TRH-LI was estimated by RIA with antiserum 4319, which binds most tripeptides that share the N- and C-terminal amino acids with TRH (pGlu-His-ProNH2). In addition, LH and FSH were measured in these sera b

Comparing the effectiveness of bevacizumab to ranibizumab in patients with exudative age-related macular degeneration. The BRAMD study

Purpose: To compare the effectiveness of bevacizumab and ranibizumab in the treatment of exudative age-related macular degeneration (AMD). Design: Multicentre, randomized, controlled, double-masked clinical trial in 327 patients. The noninferiority margin was 4 letters. Patients: Patients ≥ 60 years of age with primary or recurrent sub- or juxtafoveal choroidal neovascularization (CNV) secondary to AMD with a total area of CNV < 12 disc areas and a best corrected visual acuity (BCVA) score between 20 and 78 letters on an EDTRS like chart in the study eye. Methods: Monthly intravitreal injections with 1.25 mg bevacizumab or 0.5 mg ranibizumab were given during one year. Intention to treat with last observation carried forward analysis was performed. Main Outcome Measures: Primary outcome was the change in BCVA in the study eye from baseline to 12 months. Results: The mean gain in BCVA was 5.1 (±14.1) letters in the bevacizumab group (n = 161) and 6.4 (±12.2) letters in the ranibizumab group (n = 166) (p = 0.37). The lower limit of the 95% confidence interval of the difference in BCVA gain was 3.72. The response to bevacizumab was more varied; 24% of patients showed a gain of ≥15 letters, 11% a loss of ≥15 letters and 65% a gain or loss < 15 letters compared to 19%, 5% and 76% respectively for ranibizumab (p = 0.038). No significant differences in absolute CRT and CRT change (p = 0.13) or in the presence of subretinal or intraretinal fluid (p = 0.14 and 0.10, respectively) were observed. However, the presence of any fluid on SD-OCT (subretinal and/or intraretinal) differed significantly (p = 0.020), with definite fluid on SD-OCT in 45% of the patients for bevacizumab versus 31% for ranibizumab. The occurrence of serious adverse events and adverse events was similar, with 34 SAEs and 256 AEs in the bevacizumab group and 37 SAEs and 299 AEs in the ranibizumab group (p = 0.87 and p = 0.48, respectively). Conclusions: Bevacizumab was not inferior to ranibizumab. The response to bevacizumab was more varied with higher percentages of both gainers and losers and more frequently observed retinal fluid on SD-OCT at 12 months when compared to the ranibizumab group. Trial Registration: Trialregister.nl NTR1704

Comparing the effectiveness and costs of Bevacizumab to Ranibizumab in patients with Diabetic Macular Edema: A randomized clinical trial (the BRDME study)

Background: The effectiveness of ranibizumab in the treatment of diabetic macular edema has been proven with large clinical trials. For bevacizumab only two clinical trials have been published and a head-to-head comparison is lacking to date. However, if proved non-inferior to ranibizumab, use of the off-label bevacizumab could reduce costs enormously without a loss in visual acuity. A cost-effectiveness study has been designed to substantiate this hypothesis. Aim: To compare the effectiveness and costs of 1.25 mg of bevacizumab to 0.5 mg ranibizumab given as monthly intravitreal injections during 6 months in patients with diabetic macular edema. It is hypothesized that bevacizumab is non-inferior to ranibizumab regarding its effectiveness. Design: This is a randomized, controlled, double masked, clinical trial in 246 patients in seven academic trial centres in The Netherlands. Outcomes: The primary outcome measure is the change in best-corrected visual acuity (BCVA) in the study eye from baseline to month 6. Secondary outcomes are the proportions of patients with a gain or loss of 15 letters or more or a BCVA of 20/40 or more at 6 months, the change in leakage on fluorescein angiography and the change in foveal thickness by optical coherence tomography at 6 months, the number of adverse events in 6 months, and the costs per quality adjusted life-year of the two treatments