Why Human Enhancement is Necessary for Successful Human Deep-space Missions.

While humans have made enormous progress in the exploration and exploitation of Earth, exploration of outer space remains beyond current human capabilities. The principal challenges lie in current space technology and engineering which includes the protection of astronauts from the hazards of working and living in the space environment. These challenges may lead to a paradoxical situation where progress in space technology and the ability to ensure acceptable risk/benefit for human space exploration becomes dissociated and the rate of scientific discovery declines.

Evaluation of Antibody Properties and Clinically Relevant Immunogenicity, Anaphylaxis, and Hypersensitivity Reactions in Two Phase III Trials of Tralokinumab in Severe, Uncontrolled Asthma.

Introduction: Tralokinumab is a monoclonal antibody (mAb) that neutralizes interleukin (IL)-13, a cytokine involved in the pathogenesis of asthma.

Objective: The objectives of this study were to characterize the potential immunogenic properties of tralokinumab and report data for anti-drug antibodies (ADAs) and hypersensitivity reactions from two phase III clinical trials.

Methods: The oligosaccharide structure of tralokinumab, Fab-arm exchange, and ADAs were characterized by standard techniques.

From Target Identification to Drug Development in Space: Using the Microgravity Assist.

The unique nature of microgravity encountered in space provides an opportunity for drug discovery and development that cannot be replicated on Earth. From the production of superior protein crystals to the identification and validation of new drug targets to microarray analyses of transcripts attenuated by microgravity, there are numerous examples which demonstrate the benefit of exploiting the space environment. Moreover, studies conducted on Space Shuttle missions, the International Space Station and other craft have had a direct benefit for drug development programmes such as those directed against reducing bone and muscle loss or increasing bone formation.

Effect of tralokinumab, an interleukin-13 neutralising monoclonal antibody, on eosinophilic airway inflammation in uncontrolled moderate-to-severe asthma (MESOS): a multicentre, double-blind, randomised, placebo-controlled phase 2 trial.

Background: The role of interleukin 13 in airway inflammation and remodelling in asthma is unclear. Tralokinumab is a human monoclonal antibody that neutralises interleukin 13. We aimed to evaluate whether tralokinumab would have an effect on airway eosinophilic infiltration, blood and sputum eosinophil concentrations, eosinophil activation, and airway remodelling.

Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Development in Rheumatoid Arthritis.

Objective: Rheumatoid arthritis (RA) is a chronic and degenerative autoimmune joint disease that leads to disability, reduced quality of life, and increased mortality. Although several synthetic and biologic disease-modifying antirheumatic drugs are available, there is still a medical need for novel drugs that control disease progression. As only 10% of experimental drug candidates for treatment of RA that enter phase I trials are eventually registered by the Food and Drug Administration, there is an immediate need for translational tools to facilitate early decision-making in drug development.

Tralokinumab for the treatment of severe, uncontrolled asthma: the ATMOSPHERE clinical development program.

Tralokinumab, a fully human IgG monoclonal antibody, specifically neutralizes IL-13. The ATMOSPHERE clinical development program comprised four randomized, placebo-controlled clinical trials and an open-label study that aimed to assess the efficacy and safety of tralokinumab for the treatment of severe, uncontrolled asthma. The two pivotal trials (STRATOS 1 and STRATOS 2; NCT02161757 and NCT02194699) evaluated the efficacy and safety of tralokinumab, with STRATOS 1 identifying a subgroup most likely to demonstrate enhanced response to treatment.

Potential Risks Related to Modulating Interleukin-13 and Interleukin-4 Signalling: A Systematic Review.

Introduction: Interleukin-13 and interleukin-4 are type-II cytokines signalling through the shared type II interleukin-4 receptor. As a result of their structural similarity, interleukin-13 and interleukin-4 have overlapping functions in the mediation of type-II-driven diseases and are, therefore, promising targets of biologic drugs currently in development for the treatment of such diseases, including asthma and atopic dermatitis.

Objective: This systematic review was conducted to assess preclinical evidence of potential safety concerns related to blockade of interleukin-13 alone or interleukin-13 and interleukin-4 in combination.

Development of a prognostic nomogram for cirrhotic patients with upper gastrointestinal bleeding.

Background And Aim: Upper gastrointestinal bleeding (UGIB) is a complication with a high mortality rate in critically ill patients presenting with cirrhosis. Today, there exist few accurate scoring models specifically designed for mortality risk assessment in critically ill cirrhotic patients with upper gastrointestinal bleeding (CICGIB). Our aim was to develop and evaluate a novel nomogram-based model specific for CICGIB.

Comparative efficacy of vasoconstrictor therapies for type 1 hepatorenal syndrome: a network meta-analysis.

The outcome of a comparative efficacy and safety of vasoconstrictor therapies for treatment of patients with type 1 hepatorenal syndrome (HRS-1) remain inconclusive. Areas covered: We searched literature databases for randomized controlled trials (RCTs) until 31 January 2016, and included ten eligible RCTs. In conclusion, terlipressin was the most efficacious vasoconstrictor drug for HRS-1, but had a higher probability of causing AEs.

Quick chronic liver failure-sequential organ failure assessment: an easy-to-use scoring model for predicting mortality risk in critically ill cirrhosis patients.

Background And Aim: Critically ill cirrhosis patients have an increased risk of morbidity and mortality, even after admission to the ICU. Our objectives were to compare the predictive accuracy of model for end-stage liver disease (MELD), MELD-Na, UK model for end-stage liver disease, and chronic liver failure-sequential organ failure assessment (CLIF-SOFA) by the development and validation of an easy-to-use prognostic model [named quick CLIF-SOFA (qCLIF-SOFA)] for early risk prediction in critically ill patients with cirrhosis.

Patients And Methods: Overall, 1460 patients were extracted from the MIMIC-III database and enrolled in this study at 30-day and 90-day follow-up.

Association of low-density lipoprotein cholesterol within the normal range and NAFLD in the non-obese Chinese population: a cross-sectional and longitudinal study.

Objectives: The relationship between normal low-density lipoprotein cholesterol (LDL-c) levels and non-alcoholic fatty liver disease (NAFLD) in non-obese individuals remains unclear. We aimed to investigate the precise prevalence and incidence of NAFLD within the normal LDL-c range in non-obese individuals.

Design: Cross-sectional and longitudinal study.

Establishment and Validation of GV-SAPS II Scoring System for Non-Diabetic Critically Ill Patients.

Background And Aims: Recently, glucose variability (GV) has been reported as an independent risk factor for mortality in non-diabetic critically ill patients. However, GV is not incorporated in any severity scoring system for critically ill patients currently. The aim of this study was to establish and validate a modified Simplified Acute Physiology Score II scoring system (SAPS II), integrated with GV parameters and named GV-SAPS II, specifically for non-diabetic critically ill patients to predict short-term and long-term mortality.

Systematic Review with Network Meta-Analysis: Antidiabetic Medication and Risk of Hepatocellular Carcinoma.

Antidiabetic medication may modify the incidence of hepatocellular carcinoma (HCC). We aimed to compare the use of different antidiabetic strategies and the incidence of HCC. PubMed, Embase.

Targeting endoplasmic reticulum stress in liver disease.

Introduction: The accumulation of unfolded protein in the endoplasmic reticulum (ER) initiates an unfolded protein response (UPR) via three signal transduction cascades, which involve protein kinase RNA-like ER kinase (PERK), inositol requiring enzyme-1α (IRE1α) and activating transcription factor-6α (ATF6α). An ER stress response is observed in nearly all physiologies related to acute and chronic liver disease and therapeutic targeting of the mechanisms implicated in UPR signaling have attracted considerable attention.

Areas Covered: This review focuses on the correlation between ER stress and liver disease and the possible targets which may drive the potential for novel therapeutic intervention.

Preoperative platelet to lymphocyte ratio is a valuable prognostic biomarker in patients with colorectal cancer.

Objectives: Recent studies suggest that an elevated preoperative platelet to lymphocyte ratio (PLR) may be considered a poor prognostic biomarker in patients with colorectal cancer (CRC). The aim of this study was to evaluate the prognostic impact of PLR in patients with CRC.

Methods: We enrolled 1314 patients who underwent surgery for CRC between 2005 and 2011.

Toll-like receptors in hepatocellular carcinoma: potential novel targets for pharmacological intervention.

Introduction: Toll-like receptors (TLRs) are expressed by a wide variety of cell types including immune cells. They play a crucial role in the inflammatory and host defense response against microorganisms, and triggering TLRs can mediate the activation of innate immunity. Furthermore, research suggests that various TLRs may function differently on different tumor cells.

Parabolic relationship between sex-specific serum high sensitive C reactive protein and non-alcoholic fatty liver disease in Chinese adults: a large population-based study.

Objectives: To evaluate the association between sex-specific serum high sensitive C reactive protein (hsCRP) levels and NAFLD in a large population-based study.

Results: From Q1 to Q4, the incidence ratios were 21.1 (95% CI 17.

Atheroprotection through SYK inhibition fails in established disease when local macrophage proliferation dominates lesion progression.

Macrophages in the arterial intima sustain chronic inflammation during atherogenesis. Under hypercholesterolemic conditions murine Ly6C(high) monocytes surge in the blood and spleen, infiltrate nascent atherosclerotic plaques, and differentiate into macrophages that proliferate locally as disease progresses. Spleen tyrosine kinase (SYK) may participate in downstream signaling of various receptors that mediate these processes.

Platelet-to-Lymphocyte Ratio: A Novel Prognostic Factor for Prediction of 90-day Outcomes in Critically Ill Patients With Diabetic Ketoacidosis.

Diabetic ketoacidosis (DKA) is a life-threatening acute complication of diabetes mellitus and the novel systemic inflammation marker platelet-to-lymphocyte ratio (PLR) may be associated with clinical outcome in patients with DKA. This study aimed to investigate the utility of PLR in predicting 90-day clinical outcomes in patients with DKA. Patient data exacted from the Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC II) database was analyzed.

Increased levels of low-density lipoprotein cholesterol within the normal range as a risk factor for nonalcoholic fatty liver disease.

Objectives: Dyslipidemia exists within the setting of NAFLD and the relationship of a normal level of low-density lipoprotein cholesterol (LDL-c) with NAFLD is largely unknown. This large population-based study aimed to investigate the association between LDL-c levels within the normal range and the incidence of NAFLD.

Methods: A total of 60527 subjects from 2 medical centers who had undergone liver ultrasonography were initially enrolled into this study.

Stratified neutrophil-to-lymphocyte ratio accurately predict mortality risk in hepatocellular carcinoma patients following curative liver resection.

Objectives: Neutrophil lymphocyte ratio (NLR) has been shown to predict prognosis of cancers in several studies. This study was designed to evaluate the impact of stratified NLR in patients who have received curative liver resection (CLR) for hepatocellular carcinoma (HCC).

Methods: A total of 1659 patients who underwent CLR for suspected HCC between 2007 and 2014 were reviewed.

An analytical comparison between point-of-care uric acid testing meters.

Objective: A key goal in gout treatment is achieving sustained serum uric acid (sUA) lowering. Point-of-care test (PoCT) meters provide convenient, rapid measures of sUA levels to monitor/adjust therapy. Four commercially available sUA PoCT meters were compared qualitatively (ease of use) and quantitatively (precision/accuracy).

Kidney bioengineering in regenerative medicine: An emerging therapy for kidney disease.

The prevalence of end-stage renal disease is emerging as a serious worldwide public health problem because of the shortage of donor organs and the need to take lifelong immunosuppressive medication in patients who receive a transplanted kidney. Recently, tissue bioengineering of decellularization and recellularization scaffolds has emerged as a novel strategy for organ regeneration, and we review the critical technologies supporting these methods. We present a summary of factors associated with experimental protocols that may shed light on the future development of kidney bioengineering and we discuss the cell sources and bioreactor techniques applied to the recellularization process.

The role of lncRNAs in hepatocellular carcinoma: opportunities as novel targets for pharmacological intervention.

Long non-coding RNA (lncRNA) is commonly defined as an RNA with a length of greater than 200 nucleotides, frequently up to 100 kb. Numerous studies have shown that dysregulation of lncRNAs may directly relate to a number of human diseases, particularly in oncology where lncRNAs appear to play an important role. LncRNAs may also play a potentially novel and critical role in the development and progression of hepatocellular carcinoma (HCC).