Implementation of a Leave-behind Naloxone Program in San Francisco: A One-year Experience.

Introduction: In response to the ongoing opioid overdose crisis, US officials urged the expansion of access to naloxone for opioid overdose reversal. Since then, emergency medical services' (EMS) dispensing of naloxone kits has become an emerging harm reduction strategy.

Methods: We created a naloxone training and low-barrier distribution program in San Francisco: Project FRIEND (First Responder Increased Education and Naloxone Distribution).

Virtual Preoperative Planning and Intraoperative Navigation in Facial Prosthetic Reconstruction: A Technical Note.

This technical protocol outlines the use of computer-assisted image-guided technology for the preoperative planning and intraoperative procedures involved in implant-retained facial prosthetic treatment. A contributing factor for a successful prosthetic restoration is accurate preoperative planning to identify prosthetically driven implant locations that maximize bone contact and enhance cosmetic outcomes. Navigational systems virtually transfer precise digital planning into the operative field for placing implants to support prosthetic restorations.

Management of central giant cell granuloma with subcutaneous denosumab therapy.

Purpose: In recent years, the treatment of central giant cell granuloma (CGCG) has become focused on the inhibition of osteoclast differentiation and proliferation. Medications that were developed for the treatment of giant cell tumor of bone and bone resorption from metastatic skeletal disease have shown some success in the treatment of CGCG. The present report describes 2 cases of CGCG of the mandible that were treated effectively with subcutaneous denosumab.

Discovery, optimization, and pharmacological characterization of novel heteroaroylphenylureas antagonists of C-C chemokine ligand 2 function.

Through the application of TRAP (target-related affinity profiling), we identified a novel class of heteroaroylphenylureas that inhibit human CCL2-induced chemotaxis of monocytes/macrophages both in vitro and in vivo. This inhibition was concentration-dependent and selective with regard to other chemokines. The compounds, however, did not antagonize the binding of (125)I-labeled CCL2 to the CCR2 receptor nor did they block CCR2-mediated signal transduction responses such as calcium mobilization.

Applications of surgical navigational systems for craniofacial bone-anchored implant placement.

The following case reports describe the use of computer-assisted image-guided surgery to plan and place craniofacial bone-anchored implants (CBAI) for facial prosthetic reconstructions. During virtual planning, the soft tissue and bone visualizations are segmented from spiral computed tomography data and the patient's normal anatomy is mirrored onto the skull of the defect side, thus providing the ability to visualize the future prosthetic form. CBAI are planned in the anatomical area that leads to the best cosmetic results.

Design, synthesis, and structure-activity relationships of novel insulin receptor tyrosine kinase activators.

A novel series of symmetrical ureas of [(7-amino(2-naphthyl))sulfonyl]phenylamines were designed, synthesized, and tested for their ability to increase glucose transport in mouse 3T3-L1 adipocytes, a surrogate readout for activation of the insulin receptor (IR) tyrosine kinase (IRTK). A structure-activity relationship was established that indicated glucose transport activity was dependent on the presence of two acidic functionalities, two sulfonamide linkages, and a central urea or 2-imidazolidinone core. Compound 30 was identified as a potent and selective IRTK activator.

5-Substituted isophthalamides as insulin receptor sensitizers.

A novel series of 5-substituted isophthalamides and their structure-activity relationship as insulin receptor sensitizers is discussed.

Diarylureas are small-molecule inhibitors of insulin-like growth factor I receptor signaling and breast cancer cell growth.

In breast and certain other cancers, receptor tyrosine kinases, including the insulin-like growth factor I receptor (IGF-IR), play an important role in promoting the oncogenic process. The IGF-IR is therefore an important target for developing new anti-breast cancer therapies. An initial screening of a chemical library against the IGF-IR in breast cancer cells identified a diaryl urea compound as a potent inhibitor of IGF-IR signaling.

Early clinical experience with a new one-piece implant system in single tooth sites.

Purpose: To evaluate the clinical efficacy of a new 1-piece implant in single tooth sites.

Materials And Methods: Early clinical results were evaluated through observation and collection of survival data for 45 1-piece Direct implants (Nobel Biocare, Yorba Linda, CA). Patients ranged in age from 19 to 54 years, of which 23 were women and 12 were men.

Evaluation of ocular changes secondary to blowout fractures.

There has been extensive debate over the standard of care of orbital fractures. Entrapment, diplopia, and hypoglobus, with or without enophthalmos, are the most common clinical indications for surgical intervention. Evaluation of these injuries is often limited in the early postinjury period because of edema.

Novel cyclooxygenase-1 inhibitors discovered using affinity fingerprints.

We used protein affinity fingerprints to discover structurally novel inhibitors of cyclooxygenase-1 (COX-1) by screening a selected number of compounds, thus providing an alternative to extensive screening. From the affinity fingerprints of 19 known COX-1 inhibitors, a computational model for COX-1 inhibition was constructed and used to select candidate inhibitors from our compound library to be tested in the COX-1 assay. Subsequent refinement of the model by including affinity fingerprints of inactive compounds identified three molecules that were more potent than ibuprofen, a commonly used COX-1 inhibitor.

Proximal tibia bone harvest: review of technique, complications, and use in maxillofacial surgery.

Autologous bone grafts for alveolar ridge augmentation are the gold standard for restoring atrophic residual ridges in preprosthetic surgery. Many indications, donor sites, and techniques have been reported. The purpose of this article is to review the anatomy, surgical technique, and potential complications associated with proximal tibia bone harvest.

In vitro and in vivo prevention of HIV protease inhibitor-induced insulin resistance by a novel small molecule insulin receptor activator.

Protease inhibitor (PI) therapy for the treatment of patients infected with human immunodeficiency virus is frequently associated with insulin resistance and diabetic complications. These adverse effects of PI treatment result to a large extent from their inhibition of insulin-stimulated glucose transport. Insulin receptor (IR) activators that enhance the insulin signaling pathway could be effective in treating this resistance.

Phase I study of TLK286 (glutathione S-transferase P1-1 activated glutathione analogue) in advanced refractory solid malignancies.

Purpose: The purpose of this study was to determine the dose-limiting toxicities (DLTs), the maximum tolerated dose, and the pharmacokinetics of the novel glutathione analog TLK286 administered by i.v. infusion.

Predicting lower lip and chin response to mandibular advancement and genioplasty.

The purposes of this retrospective study were to examine the multidimensional nature of soft tissue changes associated with mandibular advancement and genioplasty and to develop predictive models. Longitudinal lateral cephalograms of 62 nongrowing patients (27 men and 35 women) were taken in centric relation with the lips in repose within 4 weeks before surgery and at least 6 months postoperatively (median postsurgical duration was 11 months). The mandibular incisor and pogonion were advanced surgically approximately 6 mm and 11 mm, respectively.

Bone reduction surgical guide for the Novum implant procedure: technical note.

The Novum System offers a unique opportunity to create a definitive, immediately loaded fixed prosthesis on the edentulous mandible for patients who meet specific presurgical criteria. Since this system is based on precisely placed implants and prefabricated bar structures, the surgical techniques are critical in obtaining a satisfactory result. It is especially important that the bone reduction required to create space for the implants and bar assembly be in the proper plane and deep enough to leave room for eventually setting and processing teeth.

Preparation of 8-substituted xanthine CVT-124 precursor by late stage pyrimidine ring closure.

To develop a novel route for the scaleable synthesis of the chiral xanthine CVT-124 (1, aka. BG9719), a method for the late stage pyrimidine ring closure of the nitrogen-protected endo 2-norbornenyl imidazole 3 was developed. The three-component coupling of benzylamine, 2-cyanoglycine ethyl ester (4), and methyl 5-norbornene-2-carboximidate hydrochloride (5) was demonstrated to achieve 3 in 23-46% isolated yields.

A novel small molecule that directly sensitizes the insulin receptor in vitro and in vivo.

Insulin resistance, an important feature of type 2 diabetes, is manifested as attenuated insulin receptor (IR) signaling in response to insulin binding. A drug that promotes the initiation of IR signaling by enhancing IR autophosphorylation should, therefore, be useful for treating type 2 diabetes. This report describes the effect of a small molecule IR sensitizer, TLK16998, on IR signaling.

A new structural class of proteasome inhibitors that prevent NF-kappa B activation.

The multicatalytic proteinase or proteasome is a highly conserved cellular structure that is responsible for the ATP-dependent proteolysis of many proteins involved in important regulatory cellular processes. We have identified a novel class of inhibitors of the chymotrypsin-like proteolytic activity of the 20S proteasome that exhibit IC50 values ranging from 0.1 to 0.