Soluble triggering receptor expressed on myeloid cells-1 for distinguishing bacterial from aseptic meningitis in adults

The aim of the present study was to evaluate whether soluble triggering receptor expressed on myeloid cells (sTREM-1) is present in the cerebrospinal fluid (CSF) of patients with acute meningitis and if its presence can predict bacterial infection. We found elevated levels of sTREM-1 in the CSF of seven of the nine (78%) patients with culture-positive specimens and in none of 12 (0%) patients with culture-negative specimens (sensitivity: 78%; specificity: 100%). The area under the receiver operating characteristic curve for sTREM-1 in the CSF as a predictor for bacterial meningitis was 0.889. This suggests that sTREM-1 is upregulated in the CSF of patients with bacterial meningitis with high specificity and that its presence can potentially assist clinicians in the diagnosis of bacterial meningitis.     

Picosecond 532-nm neodymium-doped yttrium aluminum garnet laser—a promising modality for the management of verrucous epidermal nevi

The verrucous epidermal nevus (VEN) is the most common type of epidermal nevi. As lesions can be disfiguring, treatment is often sought. Many therapeutic approaches have been reported, with variable efficacy and safety. Picosecond (PS) lasers are novel laser devices designated to target small chromophores. A side effect of these lasers is blistering due to epidermal-dermal separation. We aimed to harness this side effect of the PS lasers to treat patients with VEN. The purpose of this study was to report our experience treating VEN using a PS 532-nm laser. We present a retrospective case series of six patients with large VEN who were treated using a PS 532-nm laser (2–6 treatments, 8–10 weeks apart). Response in clinical photographs was assessed by two independent dermatologists and graded on a scale of 0 (exacerbation) to 4 (76–100% improvement). Patient satisfaction was recorded on a scale of 1–5. All patients demonstrated significant improvement. Average improvement was 3.7 on the quartile scale of improvement. Patient satisfaction rate averaged 4.7. The PS 532-nm laser is a promising novel modality for the treatment of large VEN.     

Local conformal autoencoder for standardized data coordinates

We propose a local conformal autoencoder (LOCA) for standardized data coordinates. LOCA is a deep learning-based method for obtaining standardized data coordinates from scientific measurements. Data observations are modeled as samples from an unknown, nonlinear deformation of an underlying Riemannian manifold, which is parametrized by a few normalized, latent variables. We assume a repeated measurement sampling strategy, common in scientific measurements, and present a method for learning an embedding in Rd that is isometric to the latent variables of the manifold. The coordinates recovered by our method are invariant to diffeomorphisms of the manifold, making it possible to match between different instrumental observations of the same phenomenon. Our embedding is obtained using LOCA, which is an algorithm that learns to rectify deformations by using a local z-scoring procedure, while preserving relevant geometric information. We demonstrate the isometric embedding properties of LOCA in various model settings and observe that it exhibits promising interpolation and extrapolation capabilities, superior to the current state of the art. Finally, we demonstrate LOCA’s efficacy in single-site Wi-Fi localization data and for the reconstruction of three-dimensional curved surfaces from two-dimensional projections.     

Safety,Pharmacokinetics, and Pharmacodynamics of ME-401, an Oral,Potent, and Selective Inhibitor of Phosphatidylinositol 3-Kinase P110δ, Following Single Ascending Dose Administration to Healthy Volunteers

Purpose

ME-401 is a novel selective inhibitor of phosphatidylinositol 3 kinase p110δ, an enzyme often found overexpressed and overactive in B-cell malignancies. The current study was performed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending oral doses of ME-401 in healthy volunteers.

LL-37 Opsonizes and Inhibits Biofilm Formation of Aggregatibacter actinomycetemcomitans at Subbactericidal Concentrations

Host defense peptides are immediate responders of the innate immunity that express antimicrobial, immunoregulatory, and wound-healing activities. Neutrophils are a major source for oral host defense peptides, and phagocytosis by neutrophils is a major mechanism for bacterial clearance in the gingival tissue. Dysfunction of or reduction in the numbers of neutrophils or deficiency in the LL-37 host defense peptide was each previously linked with proliferation of oral Aggregatibacter actinomycetemcomitans which resulted in an aggressive periodontal disease. Surprisingly, A. actinomycetemcomitans shows resistance to high concentrations of LL-37. In this study, we demonstrated that submicrocidal concentrations of LL-37 inhibit biofilm formation by A. actinomycetemcomitans and act as opsonins and agglutinins that greatly enhance its clearance by neutrophils and macrophages. Improved uptake of A. actinomycetemcomitans by neutrophils was mediated by their opsonization with LL-37. Enhanced phagocytosis and killing of A. actinomycetemcomitans by murine macrophage-like RAW 264.7 cells were dependent on their preagglutination by LL-37. Although A. actinomycetemcomitans is resistant to the bactericidal effect of LL-37, our results offer a rationale for the epidemiological association between LL-37 deficiency and the expansion of oral A. actinomycetemcomitans and indicate a possible therapeutic use of cationic peptides for host defense.     

Superior outcome of strut allograft-augmented plate fixation for the treatment of periprosthetic fractures around a stable femoral stem

Purpose

This study was designed to compare the outcome of two surgical approaches for treating femoral periprosthetic fractures around a stable femoral stem. The hypothesis was that plate fixation alone might be associated with a higher complication rate due to insufficient mechanical stability. We also considered that the addition of a strut allograft would contribute to fracture healing by means of osteoconduction.

Methods

We retrospectively assessed the outcome of 21 patients who sustained periprosthetic fractures around a total hip replacement system (Vancouver type B1 and type C fractures) and who were treated in our department (January 2006 and August 2011) either by plate fixation alone or by plate fixation and a strut allograft. The mean postoperative follow-up was 23 months (range 9–69 months). Eleven patients were treated by plate fixation alone (Plate Group), and 10 patients were treated by plate fixation and a deep frozen cortical strut allograft (AG Group). Functional outcome was rated by the Harris Hip scoring system. Postoperative radiographs were assessed for evidence of fracture union. Surgical failure was defined as any complication requiring surgical revision.

Results

The 21 patients included 17 females and 4 males. The average age was 79 years (range, 73–88) for the Plate Group and 82 years (range, 53–94) for the AG Group, and the average time to fracture union was 12 weeks (range, 2.5–6 months) and 12.95 weeks (range, 1.5–3) respectively. The overall failure rate was significantly higher in the Plate Group: 5 of them required revision surgery compared to none in the AG Group (p = 0.014).

Conclusion

The results of this analysis indicate that a strut allograft augmentation approach to Vancouver type B1 and type C periprosthetic fractures results in a better outcome than plate fixation alone by apparently adding mechanical stability and enhancing the biological healing process.