Structural dynamics and binding of Caenorhabditis elegans lifespan-extending lipid binding protein-3 to polyunsaturated fatty acids.

Intracellular lipid binding proteins (iLBPs) play crucial roles in lipid transport and cellular metabolism across the animal kingdom. Recently, a fat-to-neuron axis was described in Caenorhabditis elegans, in which lysosomal activity in the fat liberates polyunsaturated fatty acids (PUFAs) that signal to neurons and extend lifespan with durable fecundity. In this study, we investigate the structure and binding mechanisms of a lifespan-extending lipid chaperone, lipid binding protein-3 (LBP-3), which shuttles dihomo-γ-linolenic (DGLA) acid from intestinal fat to neurons.

Early Postoperative Prediction of Complications and Readmission After Colorectal Cancer Surgery Using an Artificial Neural Network.

Background: Early predictors of postoperative complications can risk-stratify patients undergoing colorectal cancer surgery. However, conventional regression models have limited power to identify complex nonlinear relationships among a large set of variables. We developed artificial neural network models to optimize the prediction of major postoperative complications and risk of readmission in patients undergoing colorectal cancer surgery.

FABP5-binding lipids regulate autophagy in differentiated SH-SY5Y cells.

The motor features of Parkinson's disease result from loss of dopaminergic neurons in the substantia nigra with autophagy dysfunction being closely linked to this disease. While a large body of work focusing on protein effectors of autophagy has been reported, regulation of autophagy by lipids has garnered far less attention. Therefore, we sought to identify endogenous lipid molecules that act as signaling mediators of autophagy in differentiated SH-SY5Y cells, a commonly used dopaminergic neuron-like cell model.

Perioperative and oncological outcomes following robotic en bloc multivisceral resection for colorectal cancer.

Aim: As multidisciplinary treatment strategies for colorectal cancer have improved, aggressive surgical resection has become commonplace. Multivisceral and extended resections offer curative-intent resection with significant survival benefit. However, limited data exist regarding the feasibility and oncological efficacy of performing extended resection via a minimally invasive approach.

What was old is new again: Phenotypic screening of a unique fungal library yields pyridoxatin, a promising lead against extensively resistant (AB5075).

Due to the emergence of resistance, the World Health Organization considers Gram-negative pathogen a top priority for therapeutic development. Using this priority pathogen and a phenotypic, agar plate-based assay, a unique library of extracts from 2,500 diverse fungi was screened for antimicrobial activity against a highly virulent, drug-resistant strain of (AB5075). The most potent hit from this screen was an extract from the fungus sp.

Ligand dependent interaction between PC-TP and PPARδ mitigates diet-induced hepatic steatosis in male mice.

Phosphatidylcholine transfer protein (PC-TP; synonym StarD2) is a soluble lipid-binding protein that transports phosphatidylcholine (PC) between cellular membranes. To better understand the protective metabolic effects associated with hepatic PC-TP, we generated a hepatocyte-specific PC-TP knockdown (L-Pctp) in male mice, which gains less weight and accumulates less liver fat compared to wild-type mice when challenged with a high-fat diet. Hepatic deletion of PC-TP also reduced adipose tissue mass and decreases levels of triglycerides and phospholipids in skeletal muscle, liver and plasma.

Differential Spatial Gene and Protein Expression Associated with Recurrence Following Chemoradiation for Localized Anal Squamous Cell Cancer.

The identification of transcriptomic and protein biomarkers prognosticating recurrence risk after chemoradiation of localized squamous cell carcinoma of the anus (SCCA) has been limited by a lack of available fresh tissue at initial presentation. We analyzed archival FFPE SCCA specimens from pretreatment biopsies prior to chemoradiation for protein and RNA biomarkers from patients with localized SCCA who recurred (N = 23) and who did not recur (N = 25). Tumor cells and the tumor microenvironment (TME) were analyzed separately to identify biomarkers with significantly different expression between the recurrent and non-recurrent groups.

Insurance Disparities in Access to Robotic Surgery for Colorectal Cancer.

Background: The use of the robotic approach is increasing for colorectal cancer operations, but the added cost of the platform has the potential to introduce challenges in its dissemination. We hypothesized that adoption of the robot is introducing new disparities in access to minimally invasive surgery (MIS) for colorectal cancer, especially across patient insurance groups.

Methods: This cross-sectional study analyzed surgical cases of stage I-III colorectal cancer from the National Cancer Database (NCDB) between 2010 and 2019.

Neoadjuvant Pembrolizumab in Localized Microsatellite Instability High/Deficient Mismatch Repair Solid Tumors.

Purpose: Pembrolizumab significantly improves clinical outcomes in advanced/metastatic microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) solid tumors but is not well studied in the neoadjuvant space.

Methods: This is a phase II open-label, single-center trial of localized unresectable or high-risk resectable MSI-H/dMMR tumors. Treatment is pembrolizumab 200 mg once every 3 weeks for 6 months followed by surgical resection with an option to continue therapy for 1 year followed by observation.

Conserved roles for Hnf4 family transcription factors in zebrafish development and intestinal function.

Transcription factors play important roles in the development of the intestinal epithelium and its ability to respond to endocrine, nutritional, and microbial signals. Hepatocyte nuclear factor 4 family nuclear receptors are liganded transcription factors that are critical for the development and function of multiple digestive organs in vertebrates, including the intestinal epithelium. Zebrafish have 3 hepatocyte nuclear factor 4 homologs, of which, hnf4a was previously shown to mediate intestinal responses to microbiota in zebrafish larvae.

Frontal plane balance during pre-planned and late-cued 90 degree turns while walking.

This study evaluated frontal-plane dynamic balance control during 90° left turns while walking. Ten healthy young adults performed straight-line gait, pre-planned turns, and turns cued visually (late-cued turns). We quantified rotational balance control via the range of frontal-plane angular momentum (Hf) about the center of mass (COM), and the relative positioning of the COM and the feet using the horizontal distance from the COM to the lateral edge of the base of support (lateral distance) and the mediolateral margin of stability (MOS).

Lysosome lipid signalling from the periphery to neurons regulates longevity.

Lysosomes are key cellular organelles that metabolize extra- and intracellular substrates. Alterations in lysosomal metabolism are implicated in ageing-associated metabolic and neurodegenerative diseases. However, how lysosomal metabolism actively coordinates the metabolic and nervous systems to regulate ageing remains unclear.

Transcriptional Integration of Distinct Microbial and Nutritional Signals by the Small Intestinal Epithelium.

Background & Aims: The intestine constantly interprets and adapts to complex combinations of dietary and microbial stimuli. However, the transcriptional strategies by which the intestinal epithelium integrates these coincident sources of information remain unresolved. We recently found that microbiota colonization suppresses epithelial activity of hepatocyte nuclear factor 4 nuclear receptor transcription factors, but their integrative regulation was unknown.

Definitive Intensity-Modulated Chemoradiation for Anal Squamous Cell Carcinoma: Outcomes and Toxicity of 428 Patients Treated at a Single Institution.

Background: Although intensity-modulated radiation therapy (IMRT) is considered the standard of care for the treatment of squamous cell carcinoma of the anus (SCCA), few large series have reported oncologic outcomes and toxicities. In this retrospective report, we aim to describe outcomes and toxicities after IMRT-based chemoradiation (CRT) for the treatment of SCCA, evaluate the impact of dose escalation (>54 Gy), and compare concurrent fluoropyrimidine in combination with either mitomycin or with cisplatin as chemosensitizers.

Methods: Patients treated at The University of Texas MD Anderson Cancer Center between January 1, 2003 and December 31, 2018 with IMRT-based CRT were included.

Germline Cancer Risk Profiles of Patients With Young-Onset Colorectal Cancer: Findings From a Prospective Universal Germline Testing and Telegenetics Program.

Background: Colorectal cancer is being increasingly diagnosed in people younger than 50 years. An inheritable cancer predisposition has been reported in 22% of the young-onset cases. Assessment of germline risk is critical for personalized cancer care.

Quality and Location of the Surgical Episode Mediate a Large Proportion of Socioeconomic-Based Survival Disparities in Patients with Resected Stage I-III Colon Cancer.

Introduction: Lower socioeconomic status (SES) is associated with shorter overall survival (OS) in patients with locoregional colon cancer. We aimed to estimate: (1) the proportion of SES-based OS disparities mediated by disparities in the quality and location of surgical treatment in patients with resected stage I-III colon cancer and (2) the relative importance of components of surgical quality.

Patients And Methods: We examined patients ages 18-80 years with resected stage I-III colon adenocarcinoma using the 2010-2016 National Cancer Database.

Is neoadjuvant therapy an alternative strategy to immediate surgery in locally perforated colon cancer?

Background: Perforations are a rare but serious complication of colorectal cancer. The current standard of treatment is emergent surgery followed by adjuvant chemotherapy. The concern with this approach is not only the uncertainty of achieving a R0 resection but also potential injury to adjacent vessels, nerves and ureters due to inflamed tissue planes.

Thioesterase superfamily member 1 undergoes stimulus-coupled conformational reorganization to regulate metabolism in mice.

In brown adipose tissue, thermogenesis is suppressed by thioesterase superfamily member 1 (Them1), a long chain fatty acyl-CoA thioesterase. Them1 is highly upregulated by cold ambient temperature, where it reduces fatty acid availability and limits thermogenesis. Here, we show that Them1 regulates metabolism by undergoing conformational changes in response to β-adrenergic stimulation that alter Them1 intracellular distribution.

Carrying Asymmetric Loads While Walking on a Treadmill Interferes with Lower Limb Coordination.

The purpose of this study was to investigate the effect of different load carriage modes on coordinative patterns in the lower extremities during walking. Twenty-five university students walked on a treadmill at their preferred pace under three different load conditions: symmetric load (5% of body mass in messenger bags on each shoulder hanging vertically and against the hips), asymmetric load 1 (10% of body mass in a messenger bag on one shoulder hanging vertically against the ipsilateral hip), and asymmetric load 2 (10% of body mass in a messenger bag on one shoulder with the bag draped across the trunk to the contralateral hip). Altered thigh-shank and shank-foot couplings were found for the loaded side during the stance of gait when comparing the asymmetric 1 and 2 to the symmetric load.

High Rate of Positive Circumferential Resection Margin in Colon Cancer: A National Appraisal and Call for Action.

Objective: To identify rates of positive circumferential resection margin (CRM) for colon cancer surgery in the US.

Summary Background Data: CRM is one of the most important determinants of local control in colorectal cancers. The extent to which CRM involvement exists after colon cancer surgery is unknown.