Complexity in Lipid Membrane Composition Induces Resilience to Aβ Aggregation.

The molecular origins of Alzheimer's disease are associated with the aggregation of the amyloid-β peptide (Aβ). This process is controlled by a complex cellular homeostasis system, which involves a variety of components, including proteins, metabolites, and lipids. It has been shown in particular that certain components of lipid membranes can speed up Aβ aggregation.

Smallholder farmers' knowledge and willingness to pay for insect-based feeds in Kenya.

Edible insects are increasingly being considered as sustainable alternatives to fish and soybean meals in animal feed because of their high nutritional quality and environmental benefits. However, successful introduction of a new product to the market depends on the target user's acceptance. Thus, evaluating the potential demand of insect-based feeds would provide relevant information for policy development.

Age-specific associations of glycated haemoglobin variability with cardiovascular disease and mortality in patients with type 2 diabetes mellitus: A 10- year cohort study.

Aims: To investigate the associations of increased variability in glycated haemoglobin (HbA1c) with cardiovascular disease (CVD) and mortality risk in patients with diabetes.

Materials And Methods: This prospective cohort study included 147 811 patients aged 45 to 84 years with type 2 diabetes mellitus, without CVD and with at least three HbA1c values recorded before baseline in the period 2008 to 2010. HbA1c variability was evaluated using a mixed effects model to reduce regression dilution bias.

Effects of High Anxiety Scores on Surgical and Overall Treatment Plan in Patients with Breast Cancer Treated with Neoadjuvant Therapy.

Background: Patients with newly diagnosed breast cancer and high levels of anxiety often pursue more aggressive surgical interventions. The neoadjuvant treatment (NAT) setting could provide a window of opportunity to address patients' anxiety. However, the impact of anxiety on surgical decisions in the setting of NAT for breast cancer has not been previously studied.

Synthesis and in-vitro anti-cancer evaluations of multi-methoxylated asymmetrical diarylpentanoids as intrinsic apoptosis inducer against colorectal cancer.

In the present study, a series of nine stable 3,4,5-methoxylphenyl-containing asymmetrical diarylpentanoids, derivatives of curcuminoids, have been synthesized, characterized and evaluated for their in-vitro anti-cancer potential against a panel of BRAF- and KRAS-mutated colorectal cancer cell lines including T84, LoVo and SW620, HT29, RKO and NCI-H508, respectively. Structure-activity relationship study on cytotoxicity of tested compounds suggested that the presence of meta-hydroxyl and adjacent dimethoxyl groups are crucial for enhanced cytotoxicity of diarylpentanoids. Among the evaluated analogs, 8 has been identified as the lead compound due to its highest chemotherapeutic index of 9.

Characterization of a novel type I l-asparaginase from Acinetobacter soli and its ability to inhibit acrylamide formation in potato chips.

l-Asparaginases have the potential to inhibit the formation of acrylamide, a harmful toxin formed during high temperature processing of food. A novel bacterium which produces l-asparaginase was screened. Type I l-asparaginase gene from Acinetobacter soli was cloned and expressed in Escherichia coli.

Transthyretin Inhibits Primary and Secondary Nucleations of Amyloid-β Peptide Aggregation and Reduces the Toxicity of Its Oligomers.

Alzheimer's disease is associated with the deposition of the amyloid-β peptide (Aβ) into extracellular senile plaques in the brain. In vitro and in vivo observations have indicated that transthyretin (TTR) acts as an Aβ scavenger in the brain, but the mechanism has not been fully resolved. We have monitored the aggregation process of Aβ by thioflavin T fluorescence, in the presence or absence of different concentrations of preformed seed aggregates of Aβ, of wild-type tetrameric TTR (WT-TTR), and of a variant engineered to be stable as a monomer (M-TTR).

An improved method for the rescue of recombinant Newcastle disease virus.

Reverse genetics has been used to generate recombinant Newcastle disease virus with enhanced immunogenic properties for vaccine development. The system, which involves co-transfecting the viral antigenomic plasmid with three helper plasmids into a T7 RNA polymerase-expressing cell to produce viral progenies, poses a great challenge. We have modified the standard transfection method to improve the transfection efficiency of the plasmids, resulting in a higher titer of virus progeny production.

The RNA-binding protein HuR is a negative regulator in adipogenesis.

Human antigen R (HuR) is an essential regulator of RNA metabolism, but its function in metabolism remains unclear. This study identifies HuR as a major repressor during adipogenesis. Knockdown and overexpression of HuR in primary adipocyte culture enhances and inhibits adipogenesis in vitro, respectively.

Pyruvate Kinase M2 Promotes Expression of Proinflammatory Mediators in House Dust Mite-Induced Allergic Airways Disease.

Asthma is a chronic disorder characterized by inflammation, mucus metaplasia, airway remodeling, and hyperresponsiveness. We recently showed that IL-1-induced glycolytic reprogramming contributes to allergic airway disease using a murine house dust mite model. Moreover, levels of pyruvate kinase M2 (PKM2) were increased in this model as well as in nasal epithelial cells from asthmatics as compared with healthy controls.

Effects of continuing use of aspirin on blood loss in patients who underwent unilateral total knee arthroplasty.

Purpose: Concerning the ongoing debate on the effects of continuing aspirin therapy on blood loss in knee arthroplasty, we conducted a retrospective investigation to test the hypothesis that continuation of aspirin prior total knee arthroplasty (TKA) will not cause more blood loss.

Methods: From a database of patients who underwent unilateral TKA between 2011 and 2016, we identified two groups: the aspirin group (patients continued aspirin during perioperative period) and the nonaspirin group (patients had no current or recent history of aspirin usage). We extracted and compared patient demographic information, comorbidity index, baseline serum hemoglobin (Hb), and creatinine level between the two groups.

Patient selection for a developmental therapeutics program using whole genome and Transcriptome analysis.

Introduction Given the high level of uncertainty surrounding the outcomes of early phase clinical trials, whole genome and transcriptome analysis (WGTA) can be used to optimize patient selection and study assignment. In this retrospective analysis, we reviewed the impact of this approach on one such program. Methods Patients with advanced malignancies underwent fresh tumor biopsies as part of our personalized medicine program (NCT02155621).

Metallointercalator [Ru(dppz)(PIP)] Renders BRCA Wild-Type Triple-Negative Breast Cancer Cells Hypersensitive to PARP Inhibition.

There is a need to improve and extend the use of clinically approved poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi), including for BRCA wild-type triple-negative breast cancer (TNBC). The demonstration that ruthenium(II) polypyridyl complex (RPC) metallointercalators can rapidly stall DNA replication fork progression provides the rationale for their combination alongside DNA damage response (DDR) inhibitors to achieve synergism in cancer cells. The aim of the present study was to evaluate use of the multi-intercalator [Ru(dppz)(PIP)] (dppz = dipyrido[3,2-:2',3'-]phenazine, PIP = (2-(phenyl)imidazo[4,5-][1,10]phenanthroline, Ru-PIP) alongside the PARPi olaparib and NU1025.

Frailty and functional decline after emergency abdominal surgery in the elderly: a prospective cohort study.

Background: Frailty has been associated with an increased risk of adverse postoperative outcomes in elderly patients. We examined the impact of preoperative frailty on loss of functional independence following emergency abdominal surgery in the elderly.

Methods: This prospective cohort study was performed at a tertiary hospital, enrolling patients 65 years of age and above who underwent emergency abdominal surgery from June 2016 to February 2018.

Microalgal Protein Extraction From Using Triphasic Partitioning Technique With Sonication.

Green microalgae containing various bioactive compounds and macronutrients such as lipids, carbohydrates, and proteins, have attracted much attention from the global community. Microalgae has the potential to be applied in food industries due to its high protein content, rapid growth rate, and ability to survive in harsh conditions. This study presents a simple yet efficient technique of sonication-assisted triphasic partitioning process, also known as ultrasonic-assisted three phase partitioning (UATPP), for the extraction of proteins from FSP-E.

Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer.

Background: In an earlier analysis of this phase 3 trial, ribociclib plus fulvestrant showed a greater benefit with regard to progression-free survival than fulvestrant alone in postmenopausal patients with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Here we report the results of a protocol-specified second interim analysis of overall survival.

Methods: Patients were randomly assigned in a 2:1 ratio to receive either ribociclib or placebo in addition to fulvestrant as first-line or second-line treatment.

A retrospective review of tuberculosis exposure among health care workers in a tertiary hospital.

Background: We evaluated tuberculosis (TB) acquisition rate and risk factors among health care workers (HCWs) exposed to index TB patients.

Methods: We performed a retrospective cohort study on exposed HCWs from August 2016 to January 2018 at a tertiary hospital in Singapore. Demographic factors and TB exposure episodes per HCW were obtained.

Impact of pathologic complete response on survival after neoadjuvant chemotherapy in early-stage breast cancer: a population-based analysis.

Background: Achieving a pathologic complete response (pCR) has been associated with improved long-term outcomes in clinical trials. However, the benefit of achieving pCR across subtypes and its prognostic effect on real-world outcomes has not been well described.

Methods: A retrospective analysis of the Breast Cancer Outcomes Unit database was undertaken to identify patients with stage I-III breast cancer treated with neoadjuvant chemotherapy from 2005 to 2010 in British Columbia.

Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing.

Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding of tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, and open source computational methods. Using DLP+, we have generated a resource of 51,926 single-cell genomes and matched cell images from diverse cell types including cell lines, xenografts, and diagnostic samples with limited material.

Dysregulation of the glutaredoxin/glutathionylation redox axis in lung diseases.

Glutathione is a major redox buffer, reaching millimolar concentrations within cells and high micromolar concentrations in airways. While glutathione has been traditionally known as an antioxidant defense mechanism that protects the lung tissue from oxidative stress, glutathione more recently has become recognized for its ability to become covalently conjugated to reactive cysteines within proteins, a modification known as glutathionylation (or glutathiolation or protein mixed disulfide). glutathionylation has the potential to change the structure and function of the target protein, owing to its size (the addition of three amino acids) and charge (glutamic acid).

Planning mass eradication of Helicobacter pylori infection for indigenous Taiwanese peoples to reduce gastric cancer.

Background And Aim: The aim of this study is to identify gastric cancer burden in Indigenous Taiwanese peoples and conduct a project to evaluate how to reduce the disparities most effectively in Indigenous communities.

Methods: First, we quantified the health disparities in gastric cancer in Indigenous peoples using data from the cancer registries during the period of 2006-2014. Second, we identified parameters that might be associated with Helicobacter pylori infection or help identify a good eradication strategy.

Bacterial production and direct functional screening of expanded molecular libraries for discovering inhibitors of protein aggregation.

Protein misfolding and aggregation are associated with a many human disorders, including Alzheimer's and Parkinson's diseases. Toward increasing the effectiveness of early-stage drug discovery for these conditions, we report a bacterial platform that enables the biosynthesis of molecular libraries with expanded diversities and their direct functional screening for discovering protein aggregation inhibitors. We illustrate this approach by performing, what is to our knowledge, the largest functional screen of small-size molecular entities described to date.

Evaluation of a Recombinant Newcastle Disease Virus Expressing Human IL12 against Human Breast Cancer.

The Newcastle disease virus (NDV) strain AF2240 is an avian avulavirus that has been demonstrated to possess oncolytic activity against cancer cells. However, to illicit a greater anti-cancer immune response, it is believed that the incorporation of immunostimulatory genes such as IL12 into a recombinant NDV backbone will enhance its oncolytic effect. In this study, a newly developed recombinant NDV that expresses IL12 (rAF-IL12) was tested for its safety, stability and cytotoxicity.