Mutations in ribosomal proteins and ribosomal RNA confer macrolide resistance in human Ureaplasma spp

Genetic mechanisms of macrolide resistance were investigated in six isolates of Ureaplasma spp. with erythromycin minimum inhibitory concentrations (MICs)≥ 8 μg/mL that were derived from 370 cultures obtained over a several year period. Point mutations in domain V of 23S rRNA and/or mutations in ribosomal protein L4 genes are likely to be responsible for this drug resistance. Overall, macrolide resistance was uncommon, in contrast to tetracycline resistance that was documented in 121 unique isolates (33%).     

Conatumumab (AMG 655) coated nanoparticles for targeted pro-apoptotic drug delivery

Colloidal nanoparticle drug delivery systems have attracted much interest for their ability to enable effective formulation and delivery of therapeutic agents. The selective delivery of these nanoparticles to the disease site can be enhanced by coating the surface of the nanoparticles with targeting moieties, such as antibodies. In this current work, we demonstrate that antibodies on the surface of the particles can also elicit key biological effects. Specifically, we demonstrate the induction of apoptosis in colorectal HCT116 cancer cells using PLGA nanoparticles coated with Conatumumab (AMG 655) death receptor 5-specific antibodies (DR5-NP). We show that DR5-NP preferentially target DR5-expressing cells and present a sufficient density of antibody paratopes to induce apoptosis via DR5, unlike free AMG 655 or non-targeted control nanoparticles. We also demonstrate that DR5-targeted nanoparticles encapsulating the cytotoxic drug camptothecin are effectively targeted to the tumour cells, thereby producing enhanced cytotoxic effects through simultaneous drug delivery and apoptosis induction. These results demonstrate that antibodies on nanoparticulate surfaces can be exploited for dual modes of action to enhance the therapeutic utility of the modality.     

Motivational Interviewing for adolescent substance use: A review of the literature

Motivational Interviewing (MI) is a widely-used approach for addressing adolescent substance use. Recent meta-analytic findings show small but consistent effect sizes. However, differences in intervention format and intervention design, as well as possible mediators of change, have never been reviewed. This review of the literature summarizes the most up-to-date MI interventions with adolescents, looks at differences between intervention format and design, and discusses possible theory-based mechanisms of change. Of the 39 studies included in this review, 67% reported statistically significant improved substance use outcomes. Chi square results show no significant difference between interventions using feedback or not, or interventions combined with other treatment versus MI alone. The need for systematic investigation in theory-based mechanisms of change is presented.     

Genome-wide analysis of loss of heterozygosity and copy number amplification in uterine leiomyomas using the 100K single nucleotide polymorphism array

Purpose

Uterine leiomyomas (fibroids) are benign smooth muscle tumors commonly found among reproductive-aged women. Though benign, these tumors are the leading indication for hysterectomies in the United States and cause significant morbidity. Despite the importance of this tumor in women's health, relatively little is known about the molecular etiology.

Methods

In this study, we used the Affymetrix 100K single nucleotide polymorphism (SNP) chip to assess whether the pattern and frequency of genome-wide loss of heterozygosity (LOH) and copy number amplifications is associated with clinical heterogeneity.

Results

Thirty-seven tumors with varying sizes and histology from eleven patients were analyzed. LOH was observed in 4/37 tumors (10.8%) and significantly associated with large-sized tumors (p < 0.0014). Two tumors revealed hemizygosity on chromosome 7q, a region that has been consistently reported to have LOH. Additionally, we detected one novel region of LOH, 16p13.11 in one tumor (2.7%). Copy number amplifications were observed on all chromosomes; however, most were low-level amplifications and only detected in a single tumor. One region of amplification at 3p26.3 was detected in four tumors.

Conclusions

Despite the use of a high-density SNP platform, our results suggest that genome-wide LOH and copy number amplifications are infrequent events and generally do not determine clinical and histologic characteristics of this disease.