An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to hydroxychloroquine

In this work the susceptibility of mobile and cystic forms of Borrelia burgdorferi to hydroxychloroquine (HCQ) was studied. The minimalba ctericidal concentration (MBC) of HCQ against the mobile spirochetes was >32 μg/mlat 37°C, and >128 μg/ml at 30°C. Incubation with HCQ significantly reduced the conversion of mobile spirochetes to cystic forms. When incubated at 37°C, the MBC for young biologically active cysts (1-day old) was >8 μg/ml, but it was >32 μg/ml for old cysts (1-week old). Acridine orange staining, dark-field microscopy and transmission electron microscopy revealed that the contents of the cysts were partly degraded when the concentration of HCQ was ≥MBC. At high concentrations of HCQ (256 lg/ml) about 95% of the cysts were ruptured. When the concentration of HCQ was ≥MBC, core structures did not develop inside the cysts, and the amount of RNA in these cysts decreased significantly. Spirochetal structures inside the cysts dissolved in the presence of high concentrations of HCQ. When the concentration of HCQ was ≥MBC, the core structures inside the cysts were eliminated. These observations may be valuable in the treatment of resistant infections caused by B. burgdorferi, and suggest that a combination of HCQ and a macrolide antibiotic could eradicate both cystic and mobile forms of B. burgdorferi

Defining the fracture population in a pragmatic multicentre randomised controlled trial : PROFHER and the Neer classification of proximal humeral fractures

OBJECTIVES: Accurate characterisation of fractures is essential in fracture management trials. However, this is often hampered by poor inter-observer agreement. This article describes the practicalities of defining the fracture population, based on the Neer classification, within a pragmatic multicentre randomised controlled trial in which surgical treatment was compared with non-surgical treatment in adults with displaced fractures of the proximal humerus involving the surgical neck. METHODS: The trial manual illustrated the Neer classification of proximal humeral fractures. However, in addition to surgical neck displacement, surgeons assessing patient eligibility reported on whether either or both of the tuberosities were involved. Anonymised electronic versions of baseline radiographs were sought for all 250 trial participants. A protocol, data collection tool and training presentation were developed and tested in a pilot study. These were then used in a formal assessment and classification of the trial fractures by two independent senior orthopaedic shoulder trauma surgeons. RESULTS: Two or more baseline radiographic views were obtained for each participant. The independent raters confirmed that all fractures would have been considered for surgery in contemporaneous practice. A full description of the fracture population based on the Neer classification was obtained. The agreement between the categorisation at baseline (tuberosity involvement) and Neer classification as assessed by the two raters was only fair (kappa 0.29). However, this disparity did not appear to affect trial findings, specifically in terms of influencing the effect of treatment on the primary outcome of the trial. CONCLUSIONS: A key reporting requirement, namely the description of the fracture population, was achieved within the context of a pragmatic multicentre randomised clinical trial. This article provides important guidance for researchers designing similar trials on fracture management.Cite this article: H. H. G. Handoll, S. D. Brealey, L. Jefferson, A. Keding, A. J. Brooksbank, A. J. Johnstone, J. J. Candal-Couto, A. Rangan. Defining the fracture population in a pragmatic multicentre randomised controlled trial: PROFHER and the Neer classification of proximal humeral fractures.Bone Joint Res 2016;5:481-489. DOI: 10.1302/2046-3758.510.BJR-2016-0132.R1

Association between multiple sclerosis and cystic structures in cerebrospinal fluid

Abstract Background: The aim of the study was to search for infectious agents in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). Patients and Methods: CSF from ten patients with the diagnosis relapsing remitting MS and from five controls without MS were examined by transmission electron microscopy (TEM), dark field microscopy (DF), interference contrast microscopy (ICM) and UV-microscopic examination of acridine orange staining (AO). All CSF samples from patients and controls were cultured. Results: Cystic structures were observed in CSF of all ten patients by AO and TEM. DF revealed eight cyst-positive patients out of nine. One of five control persons had such structures in the CSF; this person had suffered from erythema migrans. Spirochete or rod-like structures emerged after culturing two of the MS patient CSF samples and these structures could be propagated. Conclusion: A significant association of CSF cysts and MS was identified in this small study among residents in a coastal area of southern Norway. The cysts could be of spirochetal origin. Our study may encourage other researchers to study larger patient groups

Gene Expression and Distribution of Key Bone Turnover Markers in the Callus of Estrogen-Deficient, Vitamin D-Depleted Rats

An experimental rat model was used to test the hypothesis that in osteoporosis (OP) the molecular composition of the extracellular matrix in the fracture callus is disturbed. OP was induced at 10 weeks of age by ovariectomy and a vitamin D3-deficient diet, and sham-operated animals fed normal diet served as controls. Three months later a closed tibial fracture was made and stabilized with an intramedullary nail. After 3 and 6 weeks of healing, the animals were killed and the fracture calluses examined with global gene expression, in situ mRNA expression, and ultrastructural protein distribution of four bone turnover markers: osteopontin, bone sialoprotein, tartrate-resistant acid phosphatase, and cathepsin K. Global gene expression showed a relatively small number of differently regulated genes, mostly upregulated and at 3 weeks. The four chosen markers were not differently regulated, and only minor differences in the in situ mRNA expression and ultrastructural protein distribution were detected. Gene expression and composition of fracture calluses are not generally disturbed in experimental OP

The Danish Shoulder Arthroplasty Registry: clinical outcome and short-term survival of 2,137 primary shoulder replacements

The Danish Shoulder Arthroplasty Registry (DSR) was established in 2004. Data are reported electronically by the surgeons. Patient-reported outcome is collected 10–14 months postoperatively using the Western Ontario osteoarthritis of the shoulder index (WOOS). 2,137 primary shoulder arthroplasties (70% women) were reported to the registry between January 2006 and December 2008. Mean age at surgery was 69 years (SD 12). The most common indications were a displaced proximal humeral fracture (54%) or osteoarthritis (30%). 61% were stemmed hemiarthroplasties, 28% resurfacing hemiarthroplasties, 8% reverse shoulder arthroplasties, and 3% total arthroplasties. Median WOOS was 59% (IQR: 37–82). 5% had been revised by the end of June 2010. The most frequent indications for revision were dislocation or glenoid attrition

Anomalous Behavior Of The Complex Conductivity Of Y_{1-x}Pr_xBa_2Cu_3O_7 Observed With THz Spectroscopy

We have measured the electrodynamic properties of Y_{1-x}Pr_xBa_2Cu_3O_7 single crystal thin films as a function of temperature using coherent THz-time-domain spectroscopy. We obtain directly the complex conductivity $\sigma=\sigma_1+i\sigma_2$, the London penetration depth $\lambda_L$, the plasma frequency $\omega_p$, and the quasiparticle scattering rate $1/\tau$. We find that $1/\tau$ drops exponentially rapidly with $T$ below the critical temperature in {\em all} the superconducting samples, implying that this behavior is a {\em signature} of high-$T_c$ superconductivity. The plasma frequency decreases with increasing Pr content, providing evidence that Pr depletes carriers, leaving the CuO planes {\em underdoped}. Both the conductivity in the THz region and the dc resistivity yield evidence for the opening of a spin gap {\em above} $T_c$.Comment: 9 pages, REVTEX 3.

Universal relationship between the penetration depth and the normal-state conductivity in YBaCuO

The absolute values of the conductivity in the normal state sigma_n and of the low temperature penetration depths lambda(0) were measured for a number of different samples of the YBaCuO family. We found a striking correlation between sigma_n and 1/lambda^2, regardless of doping, oxygen reduction or defects, thus providing a simple method to predict the superconducting penetration depth and to have an estimate of the sample quality by measuring the normal-state conductivity.Comment: 7 pages, 1 figure, Europhys. Lett., accepte

Observation of inhibited electron-ion coupling in strongly heated graphite

Creating non-equilibrium states of matter with highly unequal electron and lattice temperatures (Tele≠Tion) allows unsurpassed insight into the dynamic coupling between electrons and ions through time-resolved energy relaxation measurements. Recent studies on low-temperature laser-heated graphite suggest a complex energy exchange when compared to other materials. To avoid problems related to surface preparation, crystal quality and poor understanding of the energy deposition and transport mechanisms, we apply a different energy deposition mechanism, via laser-accelerated protons, to isochorically and non-radiatively heat macroscopic graphite samples up to temperatures close to the melting threshold. Using time-resolved x ray diffraction, we show clear evidence of a very small electron-ion energy transfer, yielding approximately three times longer relaxation times than previously reported. This is indicative of the existence of an energy transfer bottleneck in non-equilibrium warm dense matter

The skeletal phenotype of chondroadherin deficient mice

Chondroadherin, a leucine rich repeat extracellular matrix protein with functions in cell to matrix interactions, binds cells via their a2b1 integrin as well as via cell surface proteoglycans, providing for different sets of signals to the cell. Additionally, the protein acts as an anchor to the matrix by binding tightly to collagens type I and II as well as type VI. We generated mice with inactivated chondroadherin gene to provide integrated studies of the role of the protein. The null mice presented distinct phenotypes with affected cartilage as well as bone. At 3–6 weeks of age the epiphyseal growth plate was widened most pronounced in the proliferative zone. The proteome of the femoral head articular cartilage at 4 months of age showed some distinct differences, with increased deposition of cartilage intermediate layer protein 1 and fibronectin in the chondroadherin deficient mice, more pronounced in the female. Other proteins show decreased levels in the deficient mice, particularly pronounced for matrilin-1, thrombospondin-1 and notably the members of the a1-antitrypsin family of proteinase inhibitors as well as for a member of the bone morphogenetic protein growth factor family. Thus, cartilage homeostasis is distinctly altered. The bone phenotype was expressed in several ways. The number of bone sialoprotein mRNA expressing cells in the proximal tibial metaphysic was decreased and the osteoid surface was increased possibly indicating a change in mineral metabolism. Micro-CT revealed lower cortical thickness and increased structure model index, i.e. the amount of plates and rods composing the bone trabeculas. The structural changes were paralleled by loss of function, where the null mice showed lower femoral neck failure load and tibial strength during mechanical testing at 4 months of age. The skeletal phenotype points at a role for chondroadherin in both bone and cartilage homeostasis, however, without leading to altered longitudinal growth