An effective pre-treatment method for eliminating interference by serum albumin for analysis of anti-rHSA antibodies.

Analysis of anti-drug antibodies (ADAs) is important for risk assessment in clinical trials. ADA detection can be very difficult in the presence of high circulating levels of drugs or target proteins. We present an effective pretreatment method for eliminating interference by endogenous albumin for analyses of recombinant human serum albumin (rHSA) ADAs. Polyethylene glycol (PEG) precipitation was used to extract albumin-ADA immune complexes from serum samples. Following acid dissociation, albumin-reactive antibodies could be detected through an electrochemiluminescence (ECL) method. Normal human serum was used to establish detectable cut points. Goat anti-human albumin was used as the positive control to evaluate the assay performance. With regard to detection of anti-HSA antibodies, pretreatment with PEG could reduce the interference from albumin in serum. We discovered that the optimized PEG precipitation and acid dissociation (PandA) method had good performance in terms of sensitivity, drug tolerance, and selectivity.

Engineered Living Oriented Electrospun Fibers Regulate Stem Cell Para-Secretion and Differentiation to Promote Spinal Cord Repair.

Living biomaterials directly couple with live cells to synthesize functional molecules and respond to dynamic environments, allowing the design, construction and application of next generation composite materials. Improving the coordination and communication between artificial materials and living cells is essential. In this study, collagen self-assembly and micro-sol electrospinning techniques are used to prepare oriented living fiber bundles that can increase the transplantation rate of stem cells in the early stages of inflammation, indirectly enhancing the dynamic regulation of stem cells during inflammation. Additionally, brain-derived neurotrophic factor (BDNF) contained in the fiber can improve the differentiation of bone marrow mesenchymal stem cells (BMSCs) into neurons once the inflammatory storm subsides. The living oriented fiber bundles fully simulate the 3D structure of the central nervous system, activate integrin ß1, promote the growth and adhesion of stem cells in the acute stage of inflammation, upregulate anti-inflammatory genes by more than twofold via BMSCs in response to inflammation, and stably release BDNF for up to 4 weeks post-inflammation storm subsidence. Finally, the BDNF induces the differentiation of BMSCs to neurons by enhancing the expression of neural-related genes, which enables the recovery of neurological functions in the later stages of spinal cord injury.

Spatiotemporal Regulation of the Bone Immune Microenvironment via Dam-Like Biphasic Bionic Periosteum for Bone Regeneration.

The bone immune microenvironment (BIM) regulates bone regeneration and affects the prognosis of fractures. However, there is currently no effective strategy that can precisely modulate macrophage polarization to improve BIM for bone regeneration. Herein, a hybridized biphasic bionic periosteum, inspired by the BIM and functional structure of the natural periosteum, is presented. The gel phase is composed of genipin-crosslinked carboxymethyl chitosan and collagen self-assembled hybrid hydrogels, which act as the "dam" to intercept IL-4 released during the initial burst from the bionic periosteum fiber phase, thus maintaining the moderate inflammatory response of M1 macrophages for mesenchymal stem cell recruitment and vascular sprouting at the acute fracture. With the degradation of the gel phase, released IL-4 cooperates with collagen to promote the polarization towards M2 macrophages, which reconfigure the local microenvironment by secreting PDGF-BB and BMP-2 to improve vascular maturation and osteogenesis twofold. In rat cranial defect models, the controlled regulation of the BIM is validated with the temporal transition of the inflammatory/anti-inflammatory process to achieve faster and better bone defect repair. This strategy provides a drug delivery system that constructs a coordinated BIM, so as to break through the predicament of the contradiction between immune response and bone tissue regeneration.

Simulation study of the mechanism of mesoscopic adsorption and the evolution of molecular dynamics of a surfactant/polymer composite on the surface of low rank coal.

In this paper, the head group, tail group, and main chain of a single type of surfactant were constructed by a mesoscopic simulation, and the interaction between the simulated surfactant and coal dust both on its own and in a composite with polyacrylamide (PAM) was studied. The molecular adsorption behavior of cetyltrimethylammonium chloride (CTAC) surfactant mixed in different ratios with PAM was also experimentally characterized. The results showed that. From the above results, we can see that CTAC and PAM can form spherical, rod-shaped, and wormlike aggregates and a network structure as their volume fraction increases in an aqueous solution. The energy spectrum showed that when CTAC adsorbed on the surface of the coal, the content of carbon on the surface decreased from 63.8 to 50.4%, and the content of oxygen increased from 35.2 to 41.8%. The study on the adsorption mechanism of surfactants and polymers on the surface of low rank coal and the hydrophilicity of low rank coal is of great significance in developing efficient dust prevention technology for low rank coal to reduce coal dust pollution.

Spiritual care for the management of Parkinson's disease: Where we are and how far can we go.

An increasing number of studies have investigated the neural networks and brain regions activated by different aspects of religious faith or spiritual practice. The extent to which religiousness and spirituality are dependent on the integrity of neural circuits is a question unique to neurological illnesses. Several studies have reported that neural networks and brain areas represent the various components of religious faith or spiritual activity in recent decades. In addition to research in healthy people, another strategy is to observe if neurological abnormalities caused by stroke, tumour, brain damage, or degenerative sickness are accompanied by an alteration in religiosity or spirituality. Similarly, Parkinson's disease (PD), an ailment characterized by dopaminergic neuron malfunction, has been utilized to explore the role of dopaminergic networks in the practice, experience, and maintenance of religious or spiritual beliefs. Case-control and priming studies have demonstrated a decline in spirituality and religion in people with PD due to dopaminergic degeneration. These studies could not adequately control for confounding variables and lacked methodological rigour. Using qualitative and quantitative assessments, a mixed-method approach might shed additional light on putative religious beliefs alterations in PD. In the current review paper, we discussed the recent research on the impact of PD on spiritual beliefs and spirituality.

Isolation and Characterization of AbTJ, an Acinetobacter baumannii Phage, and Functional Identification of Its Receptor-Binding Modules.

A. baumannii is an opportunistic pathogen and a major cause of various community-acquired infections. Strains of this species can be resistant to multiple antimicrobial agents, leaving limited therapeutic options, also lacking in methods for accurate and prompt diagnosis. In this context, AbTJ, a novel phage that infects A. baumannii MDR-TJ, was isolated and characterized, together with its two tail fiber proteins. Morphological analysis revealed that it belongs to Podoviridae family. Its host range, growth characteristics, stability under various conditions, and genomic sequence, were systematically investigated. Bioinformatic analysis showed that AbTJ consists of a circular, double-stranded 42670-bp DNA molecule which contains 62 putative open reading frames (ORFs). Genome comparison revealed that the phage AbTJ is related to the Acinetobacter phage Ab105-1phi (No. KT588074). Tail fiber protein (TFPs) gp52 and gp53 were then identified and confirmed as species-specific proteins. By using a combination of bioluminescent methods and magnetic beads, these TFPs exhibit excellent specificity to detect A. baumannii. The findings of this study can be used to help control opportunistic infections and to provide pathogen-binding modules for further construction of engineered bacteria of diagnosis and treatment.

Receptor occupancy measurement of anti-PD-1 antibody drugs in support of clinical trials.

Aim: The reliable measurement of receptor occupancy (RO) provides informative data for efficacy and safety evaluation. This study aimed to assess factors affecting RO measurement of anti-PD-1 antibodies in clinical studies. Materials & methods: RO performance was assessed using different T-cell activation markers measured by flow cytometry. The validated methodology was then used in support of a clinical study. Results: The optimized active cell population was comprised of CD45RO+ or CD45RA- T cells. The bioanalytical method was validated for inter- and intra-assay precision (coefficient of variation ≤30%) and sample storage stability for 3 days. Consistent RO saturation was observed in Phase Ia clinical trial, although receptor regulation appeared to be different. The formation of anti-drug antibodies had markedly influenced pharmacokinetics and RO. Conclusion: RO measurement in combination with pharmacokinetics and anti-drug antibodies data could allow the integrated evaluation and better understanding of efficacy and safety.

Quality and Health Literacy Demand of Online Heart Failure Information.

BACKGROUND: The ubiquity of the Internet is changing the way people obtain their health information. Although there is an abundance of heart failure information online, the quality and health literacy demand of these information are still unknown. OBJECTIVE: The purpose of this study is to evaluate the quality and health literacy demand (readability, understandability, and actionability) of the heart failure information found online. METHODS: Google, Yahoo, Bing, Ask.com, and DuckDuckGo were searched for relevant heart failure Web sites. Two independent raters then assessed the quality and health literacy demand of the included Web sites. The quality of the heart failure information was assessed using the DISCERN instrument. Readability was assessed using 7 established readability tests. Finally, understandability and actionability were assessed using the Patient Education Materials Assessment Tool for Print Materials. RESULTS: A total of 46 Web sites were included in this analysis. The overall mean quality rating was 46.0 ± 8.9 and the mean readability score was 12.6 grade reading level. The overall mean understandability score was 56.3% ± 16.2%. Finally, the overall mean actionability score was 34.7% ± 28.7%. CONCLUSIONS: The heart failure information found online was of fair quality but required a relatively high health literacy level. Web content authors need to consider not just the quality but also the health literacy demand of the information found in their Web sites. This is especially important considering that low health literacy is likely prevalent among the usual audience.

Nutritional Interventions in Heart Failure: A Systematic Review of the Literature.

BACKGROUND: Heart failure (HF) is a major health care burden and there is a growing need to develop strategies to maintain health and sustain quality of life in persons with HF. The purpose of this review is to critically appraise the components of nutrition interventions and to establish an evidence base for future advances in HF nutrition research and practice. METHODS AND RESULTS: Cinahl, Pubmed, and Embase were searched to identify articles published from 2005 to 2015. A total of 17 randomized controlled trials were included in this review. Results were divided into 2 categories of nutrition-related interventions: (1) educational and (2) prescriptive. Educational interventions improved patient outcomes such as adherence to dietary restriction in urine sodium levels and self-reported diet recall. Educational and prescriptive interventions resulted in decreased readmission rates and patient deterioration. Adherence measurement was subjective in many studies. Evidence showed that a normal-sodium diet and 1-liter fluid restriction along with high diuretic dosing enhanced B-type natriuretic peptide, aldosterone, tumor necrosis factor α, and interleukin-6 markers. CONCLUSIONS: Educational nutrition interventions positively affect patient clinical outcomes. Although clinical practice guidelines support a low-sodium diet and fluid restriction, research findings have revealed that a low-sodium diet may be harmful. Future research should examine the role of macronutrients, food quality, and energy balance in HF nutrition.