Single-cell time series analysis reveals the dynamics of HSPC response to inflammation.

Hematopoietic stem and progenitor cells (HSPCs) are known to respond to acute inflammation; however, little is understood about the dynamics and heterogeneity of these stress responses in HSPCs. Here, we performed single-cell sequencing during the sensing, response, and recovery phases of the inflammatory response of HSPCs to treatment (a total of 10,046 cells from four time points spanning the first 72 h of response) with the pro-inflammatory cytokine IFNα to investigate the HSPCs' dynamic changes during acute inflammation. We developed the essential novel computational approaches to process and analyze the resulting single-cell time series dataset.

Healthcare Providers' Knowledge of Value-Based Care in Germany: An Adapted, Mixed-Methods Approach.

Background: Value-Based Care (VBC) is being discussed to provide better outcomes to patients, with an aim to reimburse healthcare providers (HCPs) based on the quality of care they deliver. Little is known about German HCPs' knowledge of VBC. This study aims to investigate the knowledge of HCPs of VBC and to identify potential needs for further education toward implementation of VBC in Germany.

A complex proinflammatory cascade mediates the activation of HSCs upon LPS exposure in vivo.

Infections are a key source of stress to the hematopoietic system. While infections consume short-lived innate immune cells, their recovery depends on quiescent hematopoietic stem cells (HSCs) with long-term self-renewal capacity. Both chronic inflammatory stress and bacterial infections compromise competitive HSC capacity and cause bone marrow (BM) failure.

High Potential for Secondary Metabolite Production of CP157, Isolated From the Crustacean .

Secondary metabolites are key components in microbial ecology by mediating interactions between bacteria and their environment, neighboring species or host organisms. Bioactivities can be beneficial for both interaction partners or provide a competitive advantage only for the producer. Colonizers of confined habitats such as biofilms are known as prolific producers of a great number of bioactive secondary metabolites and are a potential source for novel compounds.

Interfacing With Alpha Motor Neurons in Spinal Cord Injury Patients Receiving Trans-spinal Electrical Stimulation.

Trans-spinal direct current stimulation (tsDCS) provides a non-invasive, clinically viable approach to potentially restore physiological neuromuscular function after neurological impairment, e.g., spinal cord injury (SCI).

Treatment of hyperemesis gravidarum with anthroposophic complex therapy in 3 case reports.

Background: Hyperemesis gravidarum (HG) is generally characterized by intractable nausea and vomiting which interferes with daily life. As the cause of HG has not yet been clearly identified, conventional medicine therapies address only the symptoms. Conventional treatment is also effective for a comparatively short time and may have unfavorable side effects.

Modeling Trans-Spinal Direct Current Stimulation in the Presence of Spinal Implants.

Trans-spinal direct current stimulation (tsDCS) is a technique considered for the treatment of corticospinal damage or dysfunction. TsDCS aims to induce functional modulation in the corticospinal circuitry via a direct current (DC) generated an electric field (EF). To ensure subject safety, subjects with metallic implants are generally excluded from receiving neural dc stimulation.

Changes in H-Reflex Recruitment After Trans-Spinal Direct Current Stimulation With Multiple Electrode Configurations.

Trans-spinal direct current stimulation (tsDCS) is an electro-modulatory tool with possible application in the rehabilitation of spinal cord injury. TsDCS generates a small electric field, aiming to induce lasting, functional neuromodulation in the targeted neuronal networks. Earlier studies have shown significant modulatory effects after application of lumbar tsDCS.

Modeling trans-spinal direct current stimulation for the modulation of the lumbar spinal motor pathways.

Objective: Trans-spinal direct current stimulation (tsDCS) is a potential new technique for the treatment of spinal cord injury (SCI). TsDCS aims to facilitate plastic changes in the neural pathways of the spinal cord with a positive effect on SCI recovery. To establish tsDCS as a possible treatment option for SCI, it is essential to gain a better understanding of its cause and effects.

IFNα-mediated remodeling of endothelial cells in the bone marrow niche.

In the bone marrow, endothelial cells are a major component of the hematopoietic stem cell vascular niche and are a first line of defense against inflammatory stress and infection. The primary response of an organism to infection involves the synthesis of immune-modulatory cytokines, including interferon alpha. In the bone marrow, interferon alpha induces rapid cell cycle entry of hematopoietic stem cells However, the effect of interferon alpha on bone marrow endothelial cells has not been described.

Inflammation-Induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell-like Megakaryocyte Progenitors.

Infections are associated with extensive platelet consumption, representing a high risk for health. However, the mechanism coordinating the rapid regeneration of the platelet pool during such stress conditions remains unclear. Here, we report that the phenotypic hematopoietic stem cell (HSC) compartment contains stem-like megakaryocyte-committed progenitors (SL-MkPs), a cell population that shares many features with multipotent HSCs and serves as a lineage-restricted emergency pool for inflammatory insults.

Sleep Quality Improves During Treatment With Bryophyllum pinnatum: An Observational Study on Cancer Patients.

Hypothesis: Cancer patients frequently suffer from poor sleep quality. Bryophyllum pinnatum is a herbal medication used in anthroposophic medicine, which has been shown to be associated with improvements in sleep quality during pregnancy with only few and minor or moderate side-effects reported. In this study, the sleep quality of cancer patients during treatment with B pinnatum was investigated.

Improved HSC reconstitution and protection from inflammatory stress and chemotherapy in mice lacking granzyme B.

The serine protease granzyme B (GzmB) is stored in the granules of cytotoxic T and NK cells and facilitates immune-mediated destruction of virus-infected cells. In this study, we use genetic tools to report novel roles for GzmB as an important regulator of hematopoietic stem cell (HSC) function in response to stress. HSCs lacking the GzmB gene show improved bone marrow (BM) reconstitution associated with increased HSC proliferation and mitochondrial activity.

Sleep quality in pregnancy during treatment with Bryophyllum pinnatum: an observational study.

Introduction: Poor sleep quality in pregnancy is frequent. A treatment with sedatives is problematic due to possible adverse effects for mother and embryo/foetus. In the present study, we investigated the sedative effect of Bryophyllum pinnatum, a phytotherapeutic medication used in anthroposophic medicine.

Grasp and release with surface functional electrical stimulation using a Model Predictive Control approach.

Stroke often has a disabling effect on the ability to use the hand in a functional manner. Accurate finger and thumb positioning is necessary for many activities of daily living. In the current study, the feasibility of novel FES based approaches for positioning the thumb and fingers for grasp and release of differently sized objects is evaluated.

Measurement of anti-erythropoiesis-stimulating agent IgG4 antibody as an indicator of antibody-mediated pure red cell aplasia.

Patients treated with erythropoietin-based erythropoiesis-stimulating agents (ESAs) can develop a rare but life-threatening condition called antibody-mediated pure red cell aplasia (amPRCA). The antibody characteristics in a nephrology patient with amPRCA include high antibody concentrations with neutralizing activity and a mixed IgG subclass including anti-ESA IgG4 antibodies. In contrast, anti-ESA IgG4 antibody is generally not detected in baseline samples and antibody-positive non-PRCA patients.

Development and characterization of a human antibody reference panel against erythropoietin suitable for the standardization of ESA immunogenicity testing.

Recombinant human erythropoietin (EPO) has been used therapeutically for more than two decades in the treatment of anemia. Although EPO is generally well tolerated, in rare cases, patients have developed anti-EPO antibodies that can negatively impact safety and efficacy. Therefore, the detection of antibodies against EPO is a regulatory requirement during clinical development and post-approval.

The assembly-activating protein promotes capsid assembly of different adeno-associated virus serotypes.

Adeno-associated virus type 2 (AAV2) capsid assembly requires the expression of a virally encoded assembly-activating protein (AAP). By providing AAP together with the capsid protein VP3, capsids are formed that are composed of VP3 only. Electron cryomicroscopy analysis of assembled VP3-only capsids revealed all characteristics of the wild-type AAV2 capsids.

Detection of anti-ESA antibodies in human samples from PRCA and non-PRCA patients: an immunoassay platform comparison.

Background: The immunological methods for detecting antibodies to erythropoiesis-stimulating agents (ESAs) differ in assay sensitivity. However, this parameter, routinely determined in clinical assays using a high-affinity non-human polyclonal antibody, gives a one-dimensional assessment of antibody detection. We compare three widely used immunological methods and evaluate the ability of each to detect mature human antibodies and human antibodies characteristic of an early immune response.

Considerations for optimization and validation of an in vitro PBMC derived T cell assay for immunogenicity prediction of biotherapeutics.

An immune response to a biotherapeutic can be induced when the therapeutic is processed and presented by antigen presenting cell to T helper cells. This study evaluates the performance of an in vitro assay that can elicit antigen specific effector T cell responses. Two biotherapeutics with known clinical immunogenicity [FPX1 and FPX2] were assessed for their ability to induce antigen-specific IFN-γ secreting T cells in peripheral blood mononuclear cells (PBMC).

Genetic basis and risk factors for infectious and noninfectious diseases in US Holsteins. I. Estimation of genetic parameters for single diseases and general health.

Health data collected from 1996 to 1999 from 177 herds in Minnesota and Wisconsin were analyzed to establish genetic basis for infectious and noninfectious diseases. Three types of health traits were targeted. First, available infectious conditions were used to identify animals that are superior in their general immunity (including innate immunity) for infectious diseases.

Genetic variation in bovine mononuclear leukocyte responses to dexamethasone.

The objective of this study was to determine whether bovine mononuclear leukocytes exhibit genetic variability prior to and after a glucocorticoid hormone challenge in vivo. Test animals included 60 pedigreed Holstein bulls treated on 3 consecutive days with dexamethasone and 5 untreated control bulls. Eight indicator traits of leukocyte responsiveness to dexamethasone included the percentages of circulating B cells, T cells (CD4, CD8, and workshop cluster 1 molecule expressed by bovine gammadelta T cell), major histocompatibility complex (MHC) I and II expressing cells, and mean expressions of surface MHC I and MHC II on circulating cells.

Correlations among body condition scores from various sources, dairy form, and cow health from the United States and Denmark.

The objectives of this study were to estimate genetic correlations among body condition scores (BCS) from various sources, dairy form, and measures of cow health. Body condition score and dairy form evaluated during routine type appraisal was obtained from the Holstein Association USA, Inc. A second set of BCS was obtained from Dairy Records Managements Systems (DRMS) and was recorded by producers that use PCDART dairy management software.