Crosstalk between Gut Sensory Ghrelin Signaling and Adipose Tissue Sympathetic Outflow Regulates Metabolic Homeostasis.

The stomach-derived orexigenic hormone ghrelin is a key regulator of energy homeostasis and metabolism in humans. The ghrelin receptor, growth hormone secretagogue receptor 1a (GHSR), is widely expressed in the brain and gastrointestinal vagal sensory neurons, and neuronal GHSR knockout results in a profoundly beneficial metabolic profile and protects against diet-induced obesity (DIO) and insulin resistance. Here we show that in addition to the well characterized vagal GHSR, GHSR is robustly expressed in gastrointestinal sensory neurons emanating from spinal dorsal root ganglia. Remarkably, sensory neuron GHSR deletion attenuates DIO through increased energy expenditure and sympathetic outflow to adipose tissue independent of food intake. In addition, neuronal viral tract tracing reveals prominent crosstalk between gut non-vagal sensory afferents and adipose sympathetic outflow. Hence, these findings demonstrate a novel gut sensory ghrelin signaling pathway critical for maintaining energy homeostasis.

Spinal exposure for anterior lumbar interbody fusion (ALIF) in the lateral decubitus position: anatomical and technical considerations.

PURPOSE: Single position surgery has demonstrated to reduce hospital length of stay, operative times, blood loss, postoperative pain, ileus, and complications. ALIF and LLIF surgeries offer advantages of placing large interbody devices under direct compression and can be performed by a minimally invasive approach in the lateral position. Furthermore, simultaneous access to the anterior and posterior column is possible in the lateral position without the need for patient repositioning. The purpose of this study is to outline the anatomical and technical considerations for performing anterior lumbar interbody fusion (ALIF) in the lateral decubitus position. METHODS: Surgical technique and technical considerations for reconstruction of the anterior column in the lateral position by ALIF at the L4-5 and L5-S1 levels. RESULTS: Topics outlined in this review include: Operating room layout and patient positioning; surgical anatomy and approach; vessel mobilization and retractor placement for L4-5 and L5-S1 lateral ALIF exposure, in addition to comparative technique of disc space preparation, trialing and implant placement compared to the supine ALIF procedure. CONCLUSIONS: Anterior exposure performed in the lateral decubitus position allows safe-, minimally invasive access and implant placement in ALIF. The approach requires less peritoneal and vessel retraction than in a supine position, in addition to allowing simultaneous access to the anterior and posterior columns when performing 360° Anterior-Posterior fusion.

Lateral decubitus single position anterior-posterior (AP) fusion shows equivalent results to minimally invasive transforaminal lumbar interbody fusion at one-year follow-up.

PURPOSE: This study compares perioperative and 1-year outcomes of lateral decubitus single position circumferential fusion (L-SPS) versus minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) for degenerative pathologies. METHODS: Multicenter retrospective chart review of patients undergoing AP fusion with L-SPS or MIS TLIF. Demographics and clinical and radiographic outcomes were compared using independent samples t tests and chi-squared analyses with significance set at p < 0.05. RESULTS: A total of 445 patients were included: 353 L-SPS, 92 MIS TLIF. The L-SPS cohort was significantly older with fewer diabetics and more levels fused. The L-SPS cohort had significantly shorter operative time, blood loss, radiation dosage, and length of stay compared to MIS TLIF. 1-year follow-up showed that the L-SPS cohort had higher rates of fusion (97.87% vs. 81.11%; p = 0.006) and lower rates of subsidence (6.38% vs. 38.46%; p < 0.001) compared with MIS TLIF. There were significantly fewer returns to the OR within 1 year for early mechanical failures with L-SPS (0.0% vs. 5.4%; p < 0.001). 1-year radiographic outcomes revealed that the L-SPS cohort had a greater LL (56.6 ± 12.5 vs. 51.1 ± 15.9; p = 0.004), smaller PI-LL mismatch (0.2 ± 13.0 vs. 5.5 ± 10.5; p = 0.004). There were no significant differences in amount of change in VAS scores between cohorts. Similar results were seen after propensity-matched analysis and sub-analysis of cases including L5-S1. CONCLUSIONS: L-SPS improves perioperative outcomes and does not compromise clinical or radiographic results at 1-year follow-up compared with MIS TLIF. There may be decreased rates of early mechanical failure with L-SPS.

Clinical and Molecular Spectrum of Liposarcoma.

Liposarcomas are rare malignant tumors of adipocytic differentiation. The classification of liposarcomas into four principal subtypes reflects the distinct clinical behavior, treatment sensitivity, and underlying biology encompassed by these diseases. Increasingly, clinical management decisions and the development of investigational therapeutics are informed by an improved understanding of subtype-specific molecular pathology. Well-differentiated liposarcoma is the most common subtype and is associated with indolent behavior, local recurrence, and insensitivity to radiotherapy and chemotherapy. Dedifferentiated liposarcoma represents focal progression of well-differentiated disease into a more aggressive, metastasizing, and fatal malignancy. Both of these subtypes are characterized by recurrent amplifications within chromosome 12, resulting in the overexpression of disease-driving genes that have been the focus of therapeutic targeting. Myxoid liposarcoma is characterized by a pathognomonic chromosomal translocation that results in an oncogenic fusion protein, whereas pleomorphic liposarcoma is a karyotypically complex and especially poor-prognosis subtype that accounts for less than 10% of liposarcoma diagnoses. A range of novel pharmaceutical agents that aim to target liposarcoma-specific biology are under active investigation and offer hope of adding to the limited available treatment options for recurrent or inoperable disease.

Metagenomic characterization of the effect of feed additives on the gut microbiome and antibiotic resistome of feedlot cattle.

In North America, antibiotic feed additives such as monensin and tylosin are added to the finishing diets of feedlot cattle to counter the ill-effects of feeding diets with rapidly digestible carbohydrates. While these feed additives have been proven to improve feed efficiency and reduce liver abscess incidence, how these products impact the gastrointestinal microbiota is not completely understood. In this study, we analyzed the impact of providing antibiotic feed additives to feedlot cattle using metagenome sequencing of treated and control animals. Our results indicate that use of antibiotic feed additives does not produce discernable changes at the phylum level. However, treated cattle had reduced abundance of gram-positive bacteria at the genus level. The abundance of Ruminococcus, Erysipelotrichaceae and Lachnospiraceae in the gut of treated steers was reduced. Functional analysis of the data indicates that there was only minimal impact due to the treatment in the rumen. Genes involved in detoxification were significantly increased in the rumen of AB steers. But the relative abundance of these genes was < 0.3%. However, our results did not show any correlation between the presence of antimicrobial resistance genes in the gut microbiota and the administration of antibiotic feed additives.

A biologically informed method for detecting rare variant associations.

BACKGROUND: BioBin is a bioinformatics software package developed to automate the process of binning rare variants into groups for statistical association analysis using a biological knowledge-driven framework. BioBin collapses variants into biological features such as genes, pathways, evolutionary conserved regions (ECRs), protein families, regulatory regions, and others based on user-designated parameters. BioBin provides the infrastructure to create complex and interesting hypotheses in an automated fashion thereby circumventing the necessity for advanced and time consuming scripting. PURPOSE OF THE STUDY: In this manuscript, we describe the software package for BioBin, along with type I error and power simulations to demonstrate the strengths and various customizable features and analysis options of this variant binning tool. RESULTS: Simulation testing highlights the utility of BioBin as a fast, comprehensive and expandable tool for the biologically-inspired binning and analysis of low-frequency variants in sequence data. CONCLUSIONS AND POTENTIAL IMPLICATIONS: The BioBin software package has the capability to transform and streamline the analysis pipelines for researchers analyzing rare variants. This automated bioinformatics tool minimizes the manual effort of creating genomic regions for binning such that time can be spent on the much more interesting task of statistical analyses. This software package is open source and freely available from http://ritchielab.com/software/biobin-download.

What evidence is there for the use of workplace-based assessment in surgical training?

BACKGROUND: Recent years have seen broad changes in postgraduate training with a move toward structured formative and summative evaluation of trainees' competencies using workplace-based assessment (WBA) tools. The fitness for purpose of these instruments in surgery has been much debated. The aim of this study is to explore the evidence underlying the introduction and ongoing use of WBAs in surgical training. METHODS: A critical literature review was conducted to identify studies evaluating the use of WBAs in postgraduate surgical training. The search was conducted using the electronic databases PubMed for full-text articles in English. Additional critical evaluations of the curriculum relating to WBAs were included. The articles were synthesized in a narrative review. RESULTS: The implementation of WBA requirements in surgical training has occurred despite a relative dearth of direct evidence of their efficacy and benefit. Studies and critical reviews are being regularly undertaken to ensure that supporting evidence is accrued and the drive for improvement and refinement is maintained. It is emerging that WBAs are (contrary to their current nomenclature) formative tools for feedback and hence learning. They can facilitate the progression toward expert practice at the center of the zone of proximal development and the higher levels of Miller's pyramid, but fall short--owing to their focus on competence--of guiding surgical trainees to the higher levels of Maslow's hierarchy. CONCLUSIONS: Limited evidence has potentially undermined the introduction of WBAs in surgical training to date. There are misunderstandings regarding their use as either summative or formative educational tools. These shortcomings are an opportunity for further work in examining WBAs in their current or modified form.

An overview on the production of pigment grade titania from titania-rich slag.

To recover pigment grade TiO2, operating plants all over the world use chemical processes. Slag-based technology is considered to be attractive because of low waste generation and low chemical cost due to high titanium content and is poised to replace the conventional technology. This paper provides a review of the slag-based technology with the specific aim to produce leachable slag and achieving high titania yield from recovered wastes. Leachable oxides of the lower oxidation state, such as TiO and Ti2O3, facilitate the leaching process. However, during smelting these oxides increase the viscosity of the slag. Formation of titanium carbide or carbonitride is also not desirable as it leads to resistance to the leaching of titanium. This report highlights the problems and their possible solutions to obtain leachable slag.