Serial measurements of SIRS and SEP scores to identify unique phenotypes of sepsis.

Using scoring systems in discreet microbiologic cohorts in a serial fashion to identify unique phenotypes of sepsis remains unknown. Single-center, retrospective study that screened adults who triggered the hospital's SIRS (systemic inflammatory response syndrome) based sepsis alert into culture positive (Cx +) and culture negative (Cx-) groups. Subgroups were based on the location where the SIRS alert fired. SIRS scores and a novel score called SEP were calculated at t = 0 and at 3, 6, 12, and 24 h before and after t = 0. Primary outcome was a difference in SIRS/SEP scores in Cx + or Cx- groups over time. Secondary outcomes were differences in total SIRS/SEP scores and the components constituting SIRS/SEP scores at various locations over time. The study contained 7955 patients who met inclusion criteria. Cx + and Cx- groups had increases in SIRS/SEP scores and at similar rates starting 6 hours before t = 0. Both culture groups had decreasing SIRS/SEP scores, at varying gradients compared to the change in SIRS/SEP scores seen prior to t = 0. This pattern in SIRS/SEP scores before and after t = 0 was consistent in all location subgroups. Statistically significant differences were seen in the overall SIRS/SEP scores for Cx + and Cx- groups at hours 6, 12, and 24 after t = 0, in the ED group at t = 24 h after t = 0, the floor group at t = 0 h, and in the step-down group at t = 3 h after t = 0 h. Microbiological cohorting and serial assessments may be an effective tool to identify homogenous phenotypes of sepsis.

Inflammatory mediators drive neuroinflammation in autism spectrum disorder and cerebral palsy.

Inflammation conditions are associated with autism spectrum disorder (ASD) and cerebral palsy (CP), primarily observed in the peripheral immune system. However, the extent of neuro-inflammation and neuro-immune dysregulation remains poorly studied. In this study, we analyzed the composition of cerebrospinal fluid (CSF) to uncover the inflammatory mediators driving the neuro-immune system in ASD and CP patients. Our findings revealed that ASD patients had elevated levels of four inflammatory cytokines (TNF-α, IL-4, IL-21, and BAFF) compared to controls, while CP patients exhibited increased levels of eight inflammatory cytokines (IFN-γ, GM-CSF, TNF-α, IL-2, IL-4, IL-6, IL-17A and IL-12), one anti-inflammatory cytokine (IL-10), and five growth factors (GFs) (NGF-ß, EGF, GDF-15, G-CSF and BMP-9) compared to both controls and ASD patients. Additionally, intrathecal infusion of autologous bone marrow mononuclear cells (BMMNCs) led to a slight decrease in TGF-ß and GDF-15 levels in the CSF of ASD and CP patients, respectively. Our study provides new insights into the molecular composition of CSF in ASD and CP patients, with the potential to develop more effective diagnosis methods and improved treatment for these diseases.Clinical trial registration CSF samples used in this study are from clinical trials NCT03225651, NCT05307536, NCT02569775, NCT03123562, NCT02574923, NCT05472428 and previous reports [7, 9, 17-19].

Multivalvular involvement associated with Libman-Sacks endocarditis detected by multimodality imaging: A case report.

Libman-Sacks endocarditis accounts for 6-11 percent of systemic lupus erythematosus patients and is associated with varying degrees of valvular dysfunction, increased risk for stroke and transient ischemic attacks, and increased mortality. In previous studies, left-sided valvular Libman-Sacks vegetations were more frequently detected than right sided vegetations; reported cases of bilateral involvement is very rare. A comprehensive clinical assessment and the multimodality imaging is of utmost importance in the management of systemic lupus erythematosus. In this case report, we describe a 31-year-old female patient with uncontrolled systemic lupus erythematosus initially presented with gastrointestinal symptoms but eventually had a vegetation-like structure on the posterior leaflet of the mitral valve which was revealed during routine echocardiography. Two-dimensional/three-dimensional transthoracic and transesophageal echocardiography, cardiac magnetic resonance, and cardiac computed tomography further characterized the mitral valve vegetation and revealed an additional vegetation of the pulmonary valve. Echocardiography remains the cornerstone for the detection of Libman-Sacks vegetations. Cardiac MRI and cardiac CT are useful in characterizing lesion size and effects and may prove particularly helpful in the assessment of right-sided or multivalvular endocarditis. The presence of focal brain lesions on brain MRI prompted antithrombotic therapy.

Advances in Drug Delivery Systems Based on Red Blood Cells and Their Membrane-Derived Nanoparticles.

Red blood cells (RBCs) and RBC membrane-derived nanoparticles have been historically developed as bioinspired drug delivery systems to combat the issues of premature clearance, toxicity, and immunogenicity of synthetic nanocarriers. RBC-based delivery systems possess characteristics including biocompatibility, biodegradability, and long circulation time, which make them suited for systemic administration. Therefore, they have been employed in designing optimal drug formulations in various preclinical models and clinical trials to treat a wide range of diseases. In this review, we provide an overview of the biology, synthesis, and characterization of drug delivery systems based on RBCs and their membrane including whole RBCs, RBC membrane-camouflaged nanoparticles, RBC-derived extracellular vesicles, and RBC hitchhiking. We also highlight conventional and latest engineering strategies, along with various therapeutic modalities, for enhanced precision and effectiveness of drug delivery. Additionally, we focus on the current state of RBC-based therapeutic applications and their clinical translation as drug carriers, as well as discussing opportunities and challenges associated with these systems.

Endosomal escape of nucleic acids from extracellular vesicles mediates functional therapeutic delivery.

Extracellular vesicles hold great promise as a drug delivery platform for RNA-based therapeutics. However, there is a lack of experimental evidence for the intracellular trafficking of nucleic acid cargos, specifically, whether they are capable of escaping from the endolysosomal confinement in the recipient cells to be released into the cytosol and hence, interact with their cytoplasmic targets. Here, we demonstrated how red blood cell-derived extracellular vesicles (RBCEVs) release their therapeutic RNA/DNA cargos at specific intracellular compartments characteristic of late endosomes and lysosomes. The released cargos were functional and capable of knocking down genes of interest in recipient cells, resulting in tumor suppression in vitro and in an acute myeloid leukemia murine model without causing significant toxicity. Notably, surface functionalization of RBCEVs with an anti-human CXCR4 antibody facilitated their specific uptake by CXCR4+ leukemic cells, leading to enhanced gene silencing efficiency. Our results provide insights into the cellular uptake mechanisms and endosomal escape routes of nucleic acid cargos delivered by RBCEVs which have important implications for further improvements of the RBCEV-based delivery system.

Fe2O3/diatomite materials as efficient photo-Fenton catalysts for ciprofloxacin removal.

In this study, we used Fe2O3/diatomite material system toward ciprofloxacin (CIP) photo-Fenton removal in water under visible light (vis) excitation. The characterization of Fe2O3/diatomite catalysts was determined by X-ray diffraction patterns, Fourier-transform infrared analysis, inductively coupled plasma mass spectrometry, and scanning electron microscopy. The photo-Fenton catalytic activity of the Fe2O3/diatomite was appraised by the removal efficiency of the CIP throughout the effect of the H2O2 with various parameters such as initial pH, catalyst amount, and H2O2 amount. The results indicate that 0.2 gL-1 Fe2O3/diatomite catalysts achieved the highest performance at approximately 90.03% with a 50 µL H2O2 concentration. Furthermore, the Fe2O3/diatomite catalysts have high stability, with over 80% CIP removed after five cycles. This study is inspired to develop a potential material for photo-Fenton degradation of antibiotics in wastewater.

Dynamics of Amyloid Formation from Simplified Representation to Atomistic Simulations.

Amyloid fibril formation is an intrinsic property of short peptides, non-disease proteins, and proteins associated with neurodegenerative diseases. Aggregates of the Aß and tau proteins, the α-synuclein protein, and the prion protein are observed in the brain of Alzheimer's, Parkinson's, and prion disease patients, respectively. Due to the transient short-range and long-range interactions of all species and their high aggregation propensities, the conformational ensemble of these devastating proteins, the exception being for the monomeric prion protein, remains elusive by standard structural biology methods in bulk solution and in lipid membranes. To overcome these limitations, an increasing number of simulations using different sampling methods and protein models have been performed. In this chapter, we first review our main contributions to the field of amyloid protein simulations aimed at understanding the early aggregation steps of short linear amyloid peptides, the conformational ensemble of the Aß40/42 dimers in bulk solution, and the stability of Aß aggregates in lipid membrane models. Then we focus on our studies on the interactions of amyloid peptides/inhibitors to prevent aggregation, and long amyloid sequences, including new results on a monomeric tau construct.

Photoelectrochemical water oxidation over TiO2 nanotubes modified with MoS2 and g-C3N4.

TiO2 nanotube arrays (TNAs) have been studied for photoelectrochemical (PEC) water splitting. However, there are two major barriers of TNAs, including a low photo-response and the fast charge carrier recombination in TNAs, leading to poor photocatalytic efficiency. Through a comparison of MoS2/TNAs and g-C3N4/TNAs, it was found that TNAs modified with MoS2 and g-C3N4 exhibited a current density of, respectively, 210.6 and 139.6 µA·cm-2 at an overpotential of 1.23 V vs RHE, which is 18.2 and 12 times higher than that of pure TNAs under the same conditions. The stability of the MoS2/TNAs heterojunction is higher than that of g-C3N4/TNAs.

Immunological Hallmarks for Clinical Response to BCG in Bladder Cancer.

Intravesical Bacillus Calmette-Guerin (BCG) is an effective immunotherapy for non-muscle invasive bladder cancer (NMIBC). However, recurrence and progression remain frequent warranting deeper insights into its mechanism. We herein comprehensively profiled blood and tissues obtained from NMIBC patients before, during and after BCG treatment using cytometry by time-of-flight (CyTOF) and RNA sequencing to identify the key immune subsets crucial for anti-tumor activity. We observed the temporal changes of peripheral immune subsets including NKT cells, central memory CD4+ T cells, CD8+ T cells and regulatory T cells (Treg) during the course of BCG. Gene expression analysis revealed enriched immune pathways involving in T cell activation and chemotaxis, as well as a more diversified T cell receptor repertoire in post-BCG tissues. Moreover, tissue multiplexed-immunofluorescence (mIF) showed baseline densities of non-Treg and CD8+PD-1+ T cells were predictive of response and better recurrence-free survival after BCG. Remarkably, post-BCG tissues from responders were found to be infiltrated with more active CD8+PD-1- T cells and non-Treg CD4+FOXP3- T cells; but increased exhausted CD8+PD-1+ T cells were found in non-responders. Taken together, we identified predictive biomarkers for response and uncovered the post-treatment expansion of exhausted PD-1+CD8+ T cells as key to BCG resistance, which could potentially be restored by combining with anti-PD-1 immunotherapy.

Factors Affecting Human Umbilical Cord Blood Quality Before Cryopreservation: The Importance of Birth Weight and Gestational Age.

Background: Umbilical cord blood (UCB) is a rich source of hematopoietic stem cells and is useful for the treatment of blood diseases. The cost of UCB storage is high; thus, it is necessary to evaluate the quality of UCB before collection and cryopreservation. Aim: This study aimed to determine the maternal and neonatal factors that influence UCB before selection for cryopreservation. Materials and Methods: The analysis included 403 processed UCB units. The effects of maternal characteristics including maternal age and delivery method and neonatal factors such as birth weight, gestation duration, and sex on UCB quality were determined based on the collected blood volume, total nucleated cell (TNC) count, and CD34+ cell count. Results: The neonatal birth weight influenced the collected blood volume, TNC count, and CD34+ cell count. Neonates with higher birth weights produced better quality UCB units because of increased collected blood volumes, TNC counts, and CD34+ cell counts. However, an increase in the gestational age from 35 to 41 weeks led to decreases in the collected blood volume and CD34+ cell count. Conclusion: These data may be useful for determining the optimal cord blood units for collection and cryopreservation and for advising pregnant women using private banking services.

The OPEP protein model: from single molecules, amyloid formation, crowding and hydrodynamics to DNA/RNA systems.

The OPEP coarse-grained protein model has been applied to a wide range of applications since its first release 15 years ago. The model, which combines energetic and structural accuracy and chemical specificity, allows the study of single protein properties, DNA-RNA complexes, amyloid fibril formation and protein suspensions in a crowded environment. Here we first review the current state of the model and the most exciting applications using advanced conformational sampling methods. We then present the current limitations and a perspective on the ongoing developments.

A method to manage and share anti-retroviral (ARV) therapy information of human immunodeficiency virus (HIV) patients in Vietnam.

Management of antiretroviral (ARV) drug and HIV patients data is an important component of Vietnam Administration of HIV/AIDS Control (VAAC) Department and hospitals/health care units when people often travel in other places of Vietnam; therefore, it would lead to a number of medical errors in treatment as well as patients do not adhere to ARV therapy. In this paper, we describe a system that manages and shares antiretroviral therapy information of 4438 HIV patients in three healthcare centers in Hanoi capital of Vietnam. The overall design considerations, architecture and the integration of centralized database and decentralized management for the system are also presented. The findings from this study can serve as a guide to consider in the implementation model of health care to manage and share information of patients not only in HIV infection, but also in the other chronic and non-communicable diseases.