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AIMS: The diagnosis of periprosthetic joint infection (PJI) remains demanding due to limitations of all the available diagnostic tests. The synovial fluid marker, α-defensin, is a promising adjunct for the assessment of potential PJI. The purpose of this study was to investigate the qualitative assessment of α-defensin, using Synovasure to detect or exclude periprosthetic infection in total joint arthroplasty. PATIENTS AND METHODS: We studied 50 patients (28 women, 22 men, mean age 65 years; 20 to 89) with a clinical indication for revision arthroplasty who met the inclusion criteria of this prospective diagnostic study. The presence of α-defensin was determined using the qualitative Synovasure test and compared with standard diagnostic methods for PJI. Based on modified Musculoskeletal Infection Society (MSIS) criteria, 13 cases were categorised as septic and 36 as aseptic revisions. One test was inconclusive. RESULTS: The Synovasure test achieved a sensitivity of 69% and a specificity of 94%. The positive and negative likelihood ratios were 12.46 and 0.33, respectively. A good diagnostic accuracy for PJI, with an area under the curve of 0.82, was demonstrated. Adjusted p-values using the method of Hochberg showed that Synovasure is as good at diagnosing PJI as histology (p = 0.0042) and bacteriology with one positive culture (p = 0.0327). CONCLUSION: With its ease of use and rapid results after approximately ten minutes, Synovasure may be a useful adjunct in the diagnosis of PJI. Cite this article: Bone Joint J 2017;99-B:66-72.

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The objectives of this study were to investigate a novel laser microporation technology ( P.L.E.A.S.E. Painless Laser Epidermal System) and to determine the effect of pore number and depth on the rate and extent of drug delivery across the skin. In addition, the micropores were visualized by confocal laser scanning microscopy and histological studies were used to determine the effect of laser fluence (energy applied per unit area) on pore depth. Porcine ear skin was used as the membrane for both the pore characterization and drug transport studies. Confocal images in the XY-plane revealed that the pores were typically 150-200 microm in diameter. Histological sections confirmed that fluence could be used to effectively control pore depth - low energy application (4.53 and 13.59 J/cm(2)) resulted in selective removal of the stratum corneum (20-30 microm), intermediate energies (e.g., 22.65 J/cm(2)) produced pores that penetrated the viable epidermis (60-100 microm) and higher application energies created pores that reached the dermis (>150-200 microm). The effects of pore number and pore depth on molecular transport were quantified by comparing lidocaine delivery kinetics across intact and porated skin samples. After 24h, cumulative skin permeation of lidocaine with 0 (control), 150, 300, 450 and 900 pores was 107+/-46, 774+/-110, 1400+/-344, 1653+/-437 and 1811+/-642 microg/cm(2), respectively; there was no statistically significant difference between 300, 450 and 900 pore data - probably due to the effect of drug depletion since >50% of the applied dose was delivered. Importantly, increasing fluence did not produce a statistically significant increase in lidocaine permeation; after 24h, cumulative lidocaine permeation was 1180+/-448, 1350+/-445, 1240+/-483 and 1653+/-436 microg/cm(2) at fluences of 22.65, 45.3, 90.6 and 135.9 J/cm(2), respectively. Thus, shallow pores were equally effective in delivering lidocaine. Increasing lidocaine concentration in the formulation from 10 to 25mg/ml produced a corresponding increase in permeation (at 24h, 1650+/-437 and 4005+/-1389 microg/cm(2), respectively). The validity of the porcine skin model was confirmed as transport across porcine and human skins was shown to be statistically equivalent (at 24h, 1811+/-642 and 2663+/-208 microg/cm(2), respectively). The clinical potential of the technology and its capacity to provide significantly faster delivery than conventional passive administration was demonstrated in short duration experiments involving application of a marketed lidocaine cream (LMX4) to laser-porated skin; after only 5 min of formulation application, lidocaine deposition was measured at 61.3+/-7.5 microg/cm(2). In conclusion, the results demonstrate the ability of P.L.E.A.S.E.(R) (i) to create well-defined conduits in the skin, (ii) to provide a controlled enhancement of transdermal transport and (iii) to enable improvement in both the rate and extent of drug delivery.

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Oligomers of the negatively-charged amino acids, glutamic acid, aspartic acid, and O-phospho-L-serine are adsorbed by hydroxylapatite and illite with affinities that increase with oligomer length. In the case of oligo-glutamic acids adsorbed on hydroxylapatite, addition of an extra residue results in an approximately four-fold increase in the strength of adsorption. Oligomers much longer than the 7-mer are retained tenaciously by the mineral. Repeated incubation of short oligo-glutamic acids adsorbed on hydroxylapatite or illite with activated monomer leads to the accumulation of oligomers at least 45 units long. The corresponding reactions of aspartic acid and O-phospho-L-serine on hydroxylapatite are less effective in generating long oligomers, while illite fails to accumulate substantial amounts of long oligomers of aspartic acid or of O-phospho-L-serine.

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Treatment of relatively concentrated aqueous solutions of O-phospho-serine (50 mM), aspartic acid (100 mM) or glutamic acid (100 mM) with carbonyldiimidazole leads to the formation of an activated intermediate that oligomerizes efficiently. When the concentration of amino acid is reduced tenfold, few long oligomers can be detected. Positively-charged cetyltrimethyl ammonium bromide micelles concentrate the negatively-charged activated intermediates of the amino acids at their surfaces and catalyze efficient oligomerization even from dilute solutions.

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The origin of the RNA world is not easily understood, as effective prebiotic syntheses of the components of RNA, the beta-ribofuranoside-5'-phosphates, are hard to envisage. Recognition of this difficulty has led to the proposal that other genetic systems, the components of which are more easily formed, may have preceded RNA. This raises the question of how transitions between one genetic system and another could occur. Peptide nucleic acid (PNA) resembles RNA in its ability to form double-helical complexes stabilized by Watson-Crick hydrogen bonding between adenine and thymine and between cytosine and guanine, but has a backbone that is held together by amide rather than by phosphodiester bonds. Oligonucleotides bases on RNA are known to act as templates that catalyse the non-enzymatic synthesis of their complements from activated mononucleotides, we now show that RNA oligonucleotides facilitate the synthesis of complementary PNA strands and vice versa. This suggests that a transition between different genetic systems can occur without loss of information.

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Absorption spectroscopy in (3)He and (4)He has been performed with an InGaAs single-mode distributed Bragg reflection laser diode. The laser source provides as much as 120 mW of single-mode, single-frequency output in the 1083-nm region of the spectrum. Frequency tuning of the laser diode output by means of the junction temperature allows for mode-hop-free scanning of the entire 2(3)S-2(3)P manifold in both the (3)He and (4)He absorption spectra. The authors believe this to be the first report of semiconductor laser spectroscopy at this wavelength. Such a device will have significant applications in optical pumping, atomic cooling and trapping, fundamental nuclear studies, magnetometry, and gas dynamics.

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The influence of aging on serum levels of gonadotropins (FSH and LH), testosterone and estradiol was studied in the following groups: 4 normal men (ages 30 to 50), 38 men with symptoms of the male climacteric (ages 51 to 84), 25 men with relative impotence (ages 31 to 50), 10 normal women (ages 24 to 31), and 6 menopausal women (ages 58 to 76). FSH and LH levels began to rise in men in their 40's, and the increase became more conspicuous in the later age decades. The degree of elevation was nowhere comparable to that observed in the aging women. In the male, the serum testosterone levels showed a progressive decrease from the fifth age decade onward, whereas in the female there was an increase after the menopause. Estradiol levels showed no significant change in the aged male, but they were somewhat higher than in the aged female. Exceptions to the low-testosterone and low-gonadotropin relationship were observed in individual cases and might be explained by relatively high estradiol values. Proper replacement therapy by means of estrogens for the postmenopausal female and androgens for the aging male is often of great benefit, physically and emotionally.

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PIP: Reported is a study of the effects of estradiol pellet implants, supplemented by administration of an oral progesterone for 3 to 5 days, on 120 women aged 15-39 years. Initial treatment involved 4 pellets of estradiol (25 mg each) implanted at 6-month intervals. Once inhibition of ovulation was established, the dosage was gradually reduced to 3, 2, and 1 pellet without decreased suppression of ovulation. 1 conception occurred during the entire series. There were a few complaints of breast tenderness during the first few months of treatment. Breakthrough bleeding was rare. The few cases of hypermenorrhea were corrected by extending the progesterone treatment from 3 to 5 to 7 days. No instances of amenorrhea-galactorrhea were reported. Spontaneous ovulation usually returned within 12 months of discontinuation of treatment.^ieng

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