OBJECTIVE: To determine the effectiveness of simulator training on basic arthroscopic skills utilizing a novel, low-cost arthroscopic triangulation training system.
METHODS: A randomized controlled trial of subjects without prior arthroscopy training was conducted, with participants randomized to receive either a fixed protocol of simulation training on a triangulation simulation model (30 minutes of training for 4 consecutive days), or no training. On Days 1 and 5, all participants were evaluated on 3 simulated arthroscopic tasks by an independent observer. Variables analyzed included how many times portals were changed, the time it took to complete the tasks, and the task completion rate.
METHODS: Arthrex Inc., Naples, FL.
METHODS: Thirty-six participants (92% male, average 28 ± 5 years) with no prior arthroscopy training were randomized into 2 groups, with 17 in the training group (T) and 19 in the no-training group (NT).
RESULTS: On Day 1, there was no difference in rate of task completion between the T group and NT groups (41% versus 53%, p = 0.52). On Day 5, significantly more participants in the T group completed all tasks compared to the NT group (100% versus 63%, p = 0.008). Participants in the T group had significantly improved task completion times on Day 5 versus Day 1 (p < 0.05). Participants in the NT group had a significantly improved task completion time for Task 1 on Day 5 versus Day 1 (p = 0.037); no differences were found for Tasks 2 or 3. On Day 5, participants in the T group required significantly fewer portal changes compared to the NT group (2.35 ± 2.29 versus 6.95 ± 8.55, p = 0.039).
CONCLUSIONS: Simulation training on a simple, low-cost arthroscopic triangulation training system resulted in an overall improvement in arthroscopic probing and triangulation skills within 1 week of training, with significantly decreased task completion times and increased efficiency of movement.

Renal agenesis and hypodysplasia (RHD) are major causes of pediatric chronic kidney disease and are highly genetically heterogeneous. We conducted whole-exome sequencing in 202 case subjects with RHD and identified diagnostic mutations in genes known to be associated with RHD in 7/202 case subjects. In an additional affected individual with RHD and a congenital heart defect, we found a homozygous loss-of-function (LOF) variant in SLIT3, recapitulating phenotypes reported with Slit3 inactivation in the mouse. To identify genes associated with RHD, we performed an exome-wide association study with 195 unresolved case subjects and 6,905 control subjects. The top signal resided in GREB1L, a gene implicated previously in Hoxb1 and Shha signaling in zebrafish. The significance of the association, which was p = 2.0 × 10-5 for novel LOF, increased to p = 4.1 × 10-6 for LOF and deleterious missense variants combined, and augmented further after accounting for segregation and de novo inheritance of rare variants (joint p = 2.3 × 10-7). Finally, CRISPR/Cas9 disruption or knockdown of greb1l in zebrafish caused specific pronephric defects, which were rescued by wild-type human GREB1L mRNA, but not mRNA containing alleles identified in case subjects. Together, our study provides insight into the genetic landscape of kidney malformations in humans, presents multiple candidates, and identifies SLIT3 and GREB1L as genes implicated in the pathogenesis of RHD.

Solid waste, including municipal waste and its management, is a major challenge for most cities and among the key contributors to climate change. Greenhouse gas emissions can be reduced through recovery and recycling of resources from the municipal solid waste stream. In São Paulo, Brazil, recycling cooperatives play a crucial role in providing recycling services including collection, separation, cleaning, stocking, and sale of recyclable resources. The present research attempts to measure the greenhouse gas emission reductions achieved by the recycling cooperative Cooperpires, as well as highlight its socioeconomic benefits. Methods include participant observation, structured interviews, questionnaire application, and greenhouse gas accounting of recycling using a Clean Development Mechanism methodology. The results show that recycling cooperatives can achieve important energy savings and reductions in greenhouse gas emissions, and suggest there is an opportunity for Cooperpires and other similar recycling groups to participate in the carbon credit market. Based on these findings, the authors created a simple greenhouse gas accounting calculator for recyclers to estimate their emissions reductions.

OBJECTIVE: To examine the impact of physical fitness (PF) on the association between fasting serum triglycerides (FTG) and diabetes risk and whether temporal changes in FTG predict diabetes risk in healthy middle-aged men.
METHODS: FTG and PF (bicycle exercise test) were measured in 1962 men aged 40-59 years in 1972-1975 (Survey 1) and repeated in 1387 still healthy men on average 7.3 years later (Survey 2). Diabetes was diagnosed according to WHO 1985-criteria.
RESULTS: During 35 years follow-up 202/1962 (10.3%) men developed diabetes. Compared with the lowest, the upper FTG tertile had a 2.58-fold (95% CI: 1.81-3.74) diabetes risk adjusted for age, fasting blood glucose and maternal diabetes, and a 2.29-fold (95%CI: 1.60-3.33) when also adjusting for PF. Compared with unchanged (±25%) FTG levels (n=664), FTG reduction of more than 25% (n=261) was associated with 56% lower (0.44; 95% CI: 0.24-0.75) diabetes risk, while FTG increase of more than 25% (n=462) was associated with similar risk. These associations were unchanged when adjusted for PF and PF change.
CONCLUSIONS: High FTG-levels predicted long-term diabetes risk in healthy middle-aged men, and the association was only modestly weakened when adjusted for PF. A reduction in FTG was associated with decreased diabetes risk.

An approach for evaluating and integrating genomic data in chemical risk assessment was developed based on the lessons learned from performing a case study for the chemical dibutyl phthalate. A case study prototype approach was first developed in accordance with EPA guidance and recommendations of the scientific community. Dibutyl phthalate (DBP) was selected for the case study exercise. The scoping phase of the dibutyl phthalate case study was conducted by considering the available DBP genomic data, taken together with the entire data set, for whether they could inform various risk assessment aspects, such as toxicodynamics, toxicokinetics, and dose-response. A description of weighing the available dibutyl phthalate data set for utility in risk assessment provides an example for considering genomic data for future chemical assessments. As a result of conducting the scoping process, two questions--Do the DBP toxicogenomic data inform 1) the mechanisms or modes of action?, and 2) the interspecies differences in toxicodynamics?--were selected to focus the case study exercise. Principles of the general approach include considering the genomics data in conjunction with all other data to determine their ability to inform the various qualitative and/or quantitative aspects of risk assessment, and evaluating the relationship between the available genomic and toxicity outcome data with respect to study comparability and phenotypic anchoring. Based on experience from the DBP case study, recommendations and a general approach for integrating genomic data in chemical assessment were developed to advance the broader effort to utilize 21st century data in risk assessment.

OBJECTIVE: In clinical studies, evaluating residual fiber tracts in spinal cord injuries poses serious difficulties, whereas diffusion tensor imaging (DTI) can assess alterations in fiber structural integrity. For this reason, this study aimed to determine changes in the structural integrity of residual fiber tracts via fractional anisotropy (FA) variations and fiber-tracking patterns in patients with chronic traumatic spinal cord injury (SCI).
METHODS: T2-weighted and diffusion-weighted imaging was performed on four traumatic SCI patients and three healthy volunteers using a 3.0-T MR scanner. After obtaining fiber-tracking maps, FA values were measured and analyzed in residual and remote normal and healthy cords.
RESULTS: Diffusion tensor tractography showed obvious destruction of fiber tracts in injured cords. In the healthy control subjects, averaged FA values ranged from 0.545 to 0.601, whereas all SCI patients had decreased FA values in both residual (0.220 ± 0.121) and remote normal fibers (0.535 ± 0.101). There were also statistically significant differences in FA values between residual and remote normal fibers in patients (P = 0.000) and between their residual and healthy control fibers (P = 0.000). No significant difference was found between remote normal and healthy cords (P = 0.312).
CONCLUSIONS: Specific FA variations were observed in residual fibers, suggesting that DTI may be a useful tool for evaluating residual tracts in SCI patients.

Androst-5-ene-3β,17β-diol (ADIOL) and 5α-androstane-3β,17β-diol (3β-DIOL), metabolites of dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT), respectively, are known to possess estrogenic properties. To better understand their hormonal action and roles in the proliferation of breast cancer (BC) cells, we studied their binding to sex-hormone receptors in estrogen receptor (ER)-positive (ZR-75-1 and T-47D) and ER-negative (MDA-MB-231) human BC cells. The results demonstrated that estradiol (E2), ADIOL and 3β-DIOL stimulated the proliferation of ZR-75-1 and T-47D cells, but had no effect on ER-negative cells. In the presence of estradiol, ADIOL and 3β-DIOL inhibited the estrogen-stimulated BC cell growth. This inhibition was counteracted by anti-androgens, which were unable to affect the ADIOL and 3β-DIOL stimulatory effects in E2-free medium. On the other hand, in the presence of tamoxifen, ADIOL and 3β-DIOL showed an additional anti-proliferative activity on hormone-sensitive BC cells compared with tamoxifen treatment alone. These results are similar to previous reports obtained using MCF-7 cells, which confirmed that ADIOL and 3β-DIOL stimulated estrogen-dependent BC cell growth via ERs, but inhibited growth via androgen receptors (ARs). Several steroids bind to both ER and AR in a different preference and degree, i.e. E2>estrone (E1)>ADIOL>3β-DIOL>testosterone (T)>DHT for ER and DHT>T>3β-DIOL>ADIOL>E1>E2 for AR. The relative binding affinities of ADIOL, 3β-DIOL, and E2 corresponded well to their respective potential in stimulating cell proliferation of ZR-75-1 and T-47D cells in our results. The intrinsic relationship between cell proliferation effects and binding affinities for receptors of several steroids was revealed here by a combined binding and cell study. This article is part of a Special Issue entitled \'Synthesis and biological testing of steroid derivatives as inhibitors\'.

An evaluation of the toxicogenomic data set for dibutyl phthalate (DBP) and male reproductive developmental effects was performed as part of a larger case study to test an approach for incorporating genomic data in risk assessment. The DBP toxicogenomic data set is composed of nine in vivo studies from the published literature that exposed rats to DBP during gestation and evaluated gene expression changes in testes or Wolffian ducts of male fetuses. The exercise focused on qualitative evaluation, based on a lack of available dose-response data, of the DBP toxicogenomic data set to postulate modes and mechanisms of action for the male reproductive developmental outcomes, which occur in the lower dose range. A weight-of-evidence evaluation was performed on the eight DBP toxicogenomic studies of the rat testis at the gene and pathway levels. The results showed relatively strong evidence of DBP-induced downregulation of genes in the steroidogenesis pathway and lipid/sterol/cholesterol transport pathway as well as effects on immediate early gene/growth/differentiation, transcription, peroxisome proliferator-activated receptor signaling and apoptosis pathways in the testis. Since two established modes of action (MOAs), reduced fetal testicular testosterone production and Insl3 gene expression, explain some but not all of the testis effects observed in rats after in utero DBP exposure, other MOAs are likely to be operative. A reanalysis of one DBP microarray study identified additional pathways within cell signaling, metabolism, hormone, disease, and cell adhesion biological processes. These putative new pathways may be associated with DBP effects on the testes that are currently unexplained. This case study on DBP identified data gaps and research needs for the use of toxicogenomic data in risk assessment. Furthermore, this study demonstrated an approach for evaluating toxicogenomic data in human health risk assessment that could be applied to future chemicals.

A case study was conducted, using dibutyl phthalate (DBP), to explore an approach to using toxicogenomic data in risk assessment. The toxicity and toxicogenomic data sets relative to DBP-related male reproductive developmental outcomes were considered conjointly to derive information about mode and mechanism of action. In this manuscript, we describe the case study evaluation of the toxicological database for DBP, focusing on identifying the full spectrum of male reproductive developmental effects. The data were assessed to 1) evaluate low dose and low incidence findings and 2) identify male reproductive toxicity endpoints without well-established modes of action (MOAs). These efforts led to the characterization of data gaps and research needs for the toxicity and toxicogenomic studies in a risk assessment context. Further, the identification of endpoints with unexplained MOAs in the toxicity data set was useful in the subsequent evaluation of the mechanistic information that the toxicogenomic data set evaluation could provide. The extensive analysis of the toxicology data set within the MOA context provided a resource of information for DBP in attempts to hypothesize MOAs (for endpoints without a well-established MOA) and to phenotypically anchor toxicogenomic and other mechanistic data both to toxicity endpoints and to available toxicogenomic data. This case study serves as an example of the steps that can be taken to develop a toxicological data source for a risk assessment, both in general and especially for risk assessments that include toxicogenomic data.