In-feed antibiotic effects on the swine intestinal microbiome

Antibiotics have been administered to agricultural animals for disease treatment, disease prevention, and growth promotion for over 50 y. The impact of such antibiotic use on the treatment of human diseases is hotly debated. We raised pigs in a highly controlled environment, with one portion of the littermates receiving a diet containing performance-enhancing antibiotics [chlortetracycline, sulfamethazine, and penicillin (known as ASP250)] and the other portion receiving the same diet but without the antibiotics. We used phylogenetic, metagenomic, and quantitative PCR-based approaches to address the impact of antibiotics on the swine gut microbiota. Bacterial phylotypes shifted after 14 d of antibiotic treatment, with the medicated pigs showing an increase in Proteobacteria (1-11%) compared with nonmedicated pigs at the same time point. This shift was driven by an increase in Escherichia coli populations. Analysis of the metagenomes showed that microbial functional genes relating to energy production and conversion were increased in the antibiotic-fed pigs. The results also indicate that antibiotic resistance genes increased in abundance and diversity in the medicated swine microbiome despite a high background of resistance genes in nonmedicated swine. Some enriched genes, such as aminoglycoside O-phosphotransferases, confer resistance to antibiotics that were not administered in this study, demonstrating the potential for indirect selection of resistance to classes of antibiotics not fed. The collateral effects of feeding subtherapeutic doses of antibiotics to agricultural animals are apparent and must be considered in cost-benefit analyses.     

Activation of the p53 pathway by small-molecule-induced MDM2 and MDMX dimerization

Activation of p53 tumor suppressor by antagonizing its negative regulator murine double minute (MDM)2 has been considered an attractive strategy for cancer therapy and several classes of p53-MDM2 binding inhibitors have been developed. However, these compounds do not inhibit the p53-MDMX interaction, and their effectiveness can be compromised in tumors overexpressing MDMX. Here, we identify small molecules that potently block p53 binding with both MDM2 and MDMX by inhibitor-driven homo- and/or heterodimerization of MDM2 and MDMX proteins. Structural studies revealed that the inhibitors bind into and occlude the p53 pockets of MDM2 and MDMX by inducing the formation of dimeric protein complexes kept together by a dimeric small-molecule core. This mode of action effectively stabilized p53 and activated p53 signaling in cancer cells, leading to cell cycle arrest and apoptosis. Dual MDM2/MDMX antagonists restored p53 apoptotic activity in the presence of high levels of MDMX and may offer a more effective therapeutic modality for MDMX-overexpressing cancers.     

Primary systemic amyloidosis masquerading as giant cell arteritis. case report and review of the literature

Amyloidosis is a rare disease in which a fibrillar protein is deposited in multiple human tissues. Of the 4 subtypes, the most common type involving rheumatic disease features is hemodialysis-associated amyloidosis. Herein we describe an elderly man who presented with symptoms of giant cell arteritis or systemic vasculitis and was found to have amyloidosis as demonstrated on muscle, nerve, and temporal artery biopsy.     

Construct validity of a new computer-assisted cognitive neuromotor assessment battery in normal and inpatient psychiatric samples

The construct validity of a computer-assisted battery of neuropsychological tests (CNT) was explored with psychiatric inpatients and normal volunteers. A principal components analysis of inpatient scores revealed simple reaction time, response accuracy, visuomotor skill, and complex processing and memory components. A similar factorial structure was found in normal subjects. However, complex processing and memory measures emerged as separate vigilance and memory components in volunteers. CNT tasks were correlated with nine subtests of the Neurobehavioral Cognitive Status Examination (NCSE). Simple reaction time, and complex processing and memory measures discriminated impaired from nonimpaired inpatients as defined by the NCSE. Recommendations for research on CNT, and computer-assisted tests in general, are made.     

Determination of Interrater Reliability of a Universal Evaluator Rubric to Assess Student Pharmacist Communication Skills

Objective. To evaluate the interrater reliability of a universal evaluator rubric used to assess student pharmacist communication skills during patient education sessions.Methods. Six US schools and colleges of pharmacy each submitted 10 student videos of a simulated community pharmacy patient education session and recruited two raters in each of the five rater groups (faculty, standardized patients, postgraduate year one residents, student pharmacists, and pharmacy preceptors). Raters used a rubric containing 20 items and a global assessment to evaluate student communication of 12 videos. Agreement was computed for individual items and overall rubric score within each rater group, and for each item across all rater groups. Average overall rubric agreement scores were compared between rater groups. Agreement coefficient scores were categorized as no to minimal, weak, moderate, strong, or almost perfect agreement.Results. Fifty-five raters representing five rater groups and six pharmacy schools evaluated student communication. Item agreement analysis for all raters revealed five items with no to minimal or weak agreement, 10 items with moderate agreement, one item with strong agreement, and five items with almost perfect agreement. Overall average agreement across all rater groups was 0.73 (95% CI, 0.66-0.81). The preceptor rater group exhibited the lowest agreement score of 0.68 (95% CI, 0.58-0.78), which significantly deviated from the overall average.Conclusion. While strong or almost perfect agreement scores were not observed for all rubric items, overall average interrater reliability results support the use of this rubric in a variety of raters to assess student pharmacist communication skills during patient education sessions.     

Applications of research evidence during processes to acquire approvals for syringe services program implementation in rural counties in Kentucky

IntroductionDespite decades of empirical research in the US and internationally documenting the benefits of implementing syringe services programs (SSPs), their implementation may be controversial in many jurisdictions. Better understanding how research evidence is applied during SSP implementation processes may enable the public health workforce to advocate for program scale up. This study explores applications of research evidence during processes to acquire approvals for SSP implementation in rural counties in Kentucky.MethodsIn-depth interviews were conducted among eighteen stakeholders (e.g. health department directors, SSP operators) involved in SSP implementation in rural Kentucky counties. Stakeholders were asked to describe the contexts surrounding SSP implementation processes. Interviews were transcribed and analysed for applications of research evidence. Research evidence-related quotes were subsequently categorised based on the typologies for applications of research evidence developed by Weiss et al. (instrumental, conceptual, and symbolic) and a fourth category for instances when research evidence was not used.ResultsInstrumental applications of research evidence occurred at the intrapersonal and interpersonal levels to dispel concerns about SSPs and formed the basis for implementation support. SSP proponents used research evidence in a conceptual manner to address underlying attitudes and beliefs that were not evidence-based. Participants reported symbolic research evidence applications to justify pre-existing attitudes and beliefs about meeting the public health needs of people who inject drugs. Lastly, in some instances, research evidence was met with scepticism and an unwillingness to consider its merits.ConclusionApplications of research evidence during SSP implementation approval processes in rural Kentucky counties were heterogeneous in nature. Better understanding the diversity of ways in which research evidence may be employed during SSP implementation processes may support efforts to improve the public health of people who inject drugs.

Key messages

1. Applications of research evidence during SSP implementation approval processes in rural Kentucky counties were heterogeneous in nature.
2. Instrumental applications of research evidence occurred at the intrapersonal and interpersonal levels to dispel concerns about SSPs and formed the basis for implementation support.
3. SSP proponents used research evidence in a conceptual manner to address underlying attitudes and beliefs that were not evidence-based.

     

Changes in water diffusion due to Wallerian degeneration in peripheral nerve

The authors report NMR measurements of the changes in water diffusion brought about by in vivo Wallerian degeneration due to either crush- or tie-injuries in the sciatic nerve of the frog. Using a pulsed-gradient spin-echo sequence with a diffusion measurement time of 28 ms, the degree of diffusion coefficient anisotropy {D(longitudinal)/D(transverse)} 4 weeks after injury in both crush- and tie-injured nerves (2.3 ± 0.4 and 1.7 ± 0.1, respectively) is significantly less than in normal frog sciatic nerve (3.9 ± 0.4). The decrease of anisotropy in the degenerated nerves is due to both a decrease in longitudinal diffusion and an increase in transverse diffusion. The changes in diffusion coefficients are compared with the degree of axonal and myelin breakdown observed in light and electron micrographs of the nerves.