Examining persistence of acute environmental enrichment-induced anti-sucrose craving effects in rats.

A single, overnight (acute) environmental enrichment (EE; a large environment with conspecifics and novel objects) experience robustly decreases sucrose consumption (taking) and responsiveness to sucrose-paired cues (seeking) in rats. Persisting effects of acute EE on sucrose seeking and taking have not yet been identified. In the present study, rats were trained to self-administer a 10% sucrose solution paired with a compound tone + light stimulus for 10 days in 2-h sessions.

Author Correction: Environment-responsive nanophores for therapy and treatment monitoring via molecular MRI quenching.

This Article contains an error in Figure 6. In panel b, the left-hand image is mistakenly described as showing fluorescence before treatment, while it in fact shows the same white light image as the right-hand panel without fluorescent overlay to better visualize the tumour location. A correct version of Figure 6b is presented in the accompanying Author Correction.

Aortic annulus measurement with computed tomography angiography reduces aortic regurgitation after transfemoral aortic valve replacement compared to 3-D echocardiography: a single-centre experience.

Background: Accurate assessment of the aortic annulus is crucial for successful transcatheter aortic valve replacement (TAVR), in particular to prevent paravalvular regurgitation (PVR). We compared aortic annular sizing using multidetector computed tomography (MDCT) and three-dimensional transoesophageal echocardiography (3-D TEE) to determine the predictive value of MDCT.

Methods And Results: All patients admitted for transfemoral TAVR [n = 227; 48.

Pretreatment CD34/CD38 Cell Burden as Prognostic Factor in Myelodysplastic Syndrome Patients Receiving Allogeneic Stem Cell Transplantation.

Myelodysplastic syndrome (MDS) is a highly heterogeneous clonal hematopoietic disorder. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment and is of particular interest in patients at high risk for progression to acute myeloid leukemia (AML). In MDS, CD34/CD38 cells possess MDS stem cell potential, and secondary AML (sAML) clones originate from the MDS disease stage.

FDA-approved ferumoxytol displays anti-leukaemia efficacy against cells with low ferroportin levels.

Acute myeloid leukaemia is a fatal disease for most patients. We have found that ferumoxytol (Feraheme), an FDA-approved iron oxide nanoparticle for iron deficiency treatment, demonstrates an anti-leukaemia effect in vitro and in vivo. Using leukaemia cell lines and primary acute myeloid leukaemia patient samples, we show that low expression of the iron exporter ferroportin results in a susceptibility of these cells via an increase in intracellular iron from ferumoxytol.

Metastatic risk stratification of clear cell renal cell carcinoma patients based on genomic aberrations.

Prognostic markers for the definition of the individual metastatic risk in renal cell carcinoma are still missing. The aim of our study was to establish a total number of specific aberrations (TNSA) genetic score as a new prognostic test for metastatic risk evaluation. Fluorescence in situ hybridization (FISH) was performed on isolated cell nuclei of 100 ccRCCs (50 M1/50 M0) and 100 FFPE sections (second cohort, 32 M1/68 M0).

Biological Principles of Stereotactic Body Radiation Therapy (SBRT) and Stereotactic Radiation Surgery (SRS): Indirect Cell Death.

Purpose: To review the radiobiological mechanisms of stereotactic body radiation therapy stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS).

Methods And Materials: We reviewed previous reports and recent observations on the effects of high-dose irradiation on tumor cell survival, tumor vasculature, and antitumor immunity. We then assessed the potential implications of these biological changes associated with SBRT and SRS.

Size Mismatching Increases Mortality After Lung Transplantation in Preadolescent Patients.

Background: The effect of size mismatch between donor and recipient in pediatric lung transplantation (PLTx) is currently unknown. Previous studies in adults have suggested that oversized allografts are associated with improved outcomes after lung transplantation. We investigated this relationship to quantify its effect on posttransplant outcomes in children.

Photoactivatable Prodrug of Doxazolidine Targeting Exosomes.

Natural lipid nanocarriers, exosomes, carry cell-signaling materials such as DNA and RNA for intercellular communications. Exosomes derived from cancer cells contribute to the progression and metastasis of cancer cells by transferring oncogenic signaling molecules to neighboring and remote premetastatic sites. Therefore, applying the unique properties of exosomes for cancer therapy has been expected in science, medicine, and drug discovery fields.

Health-related quality of life after radical cystectomy and ileal orthotopic neobladder: effect of detailed continence outcomes.

Purpose: To objectively quantify continence rates and to correlate continence outcomes with health-related quality of life (HRQOL) after radical cystectomy and orthotopic ileal neobladder (ONB).

Methods: Questionnaires were sent to 244 patients who underwent radical cystectomy with ONB between 2004 and 2015, and information about the current continence status was retrieved. To objectify postoperative urine loss, daytime and nocturnal pad tests were performed.

A human-derived antibody targets misfolded SOD1 and ameliorates motor symptoms in mouse models of amyotrophic lateral sclerosis.

Mutations in the gene encoding superoxide dismutase 1 (SOD1) lead to misfolding and aggregation of SOD1 and cause familial amyotrophic lateral sclerosis (FALS). However, the implications of wild-type SOD1 misfolding in sporadic forms of ALS (SALS) remain unclear. By screening human memory B cells from a large cohort of healthy elderly subjects, we generated a recombinant human monoclonal antibody (α-miSOD1) that selectively bound to misfolded SOD1, but not to physiological SOD1 dimers.

Clinical impact of clonal hematopoiesis in acute myeloid leukemia patients receiving allogeneic transplantation.

Age-related somatic mutations linked to clonal hematopoiesis have been found in apparently healthy individuals and increase the risk of developing hematologic malignancies. In acute myeloid leukemia (AML) the clinical relevance of clonal hematopoiesis remains controversial and data on patients with detectable clonal hematopoiesis, consolidated with hematopoietic stem cell transplantation are limited. We analyzed samples from 113 AML patients in complete remission prior to hematopoietic stem cell transplantation for the presence of clonal hematopoiesis-associated mutations.

Organs at Risk Considerations for Thoracic Stereotactic Body Radiation Therapy: What Is Safe for Lung Parenchyma?

Purpose: Stereotactic body radiation therapy (SBRT) has become the standard of care for inoperable early-stage non-small cell lung cancer and is often used for recurrent lung cancer and pulmonary metastases. Radiation-induced lung toxicity (RILT), including radiation pneumonitis and pulmonary fibrosis, is a major concern for which it is important to understand dosimetric and clinical predictors.

Methods And Materials: This study was undertaken through the American Association of Physicists in Medicine's Working Group on Biological Effects of Stereotactic Body Radiotherapy.

Random-Length Random Walks and Finite-Size Scaling in High Dimensions.

We address a long-standing debate regarding the finite-size scaling (FSS) of the Ising model in high dimensions, by introducing a random-length random walk model, which we then study rigorously. We prove that this model exhibits the same universal FSS behavior previously conjectured for the self-avoiding walk and Ising model on finite boxes in high-dimensional lattices. Our results show that the mean walk length of the random walk model controls the scaling behavior of the corresponding Green's function.

Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson's disease models.

Aggregation of α-synuclein (α-syn) is neuropathologically and genetically linked to Parkinson's disease (PD). Since stereotypic cell-to-cell spreading of α-syn pathology is believed to contribute to disease progression, immunotherapy with antibodies directed against α-syn is considered a promising therapeutic approach for slowing disease progression. Here we report the identification, binding characteristics, and efficacy in PD mouse models of the human-derived α-syn antibody BIIB054, which is currently under investigation in a Phase 2 clinical trial for PD.

Distinguishing True Progression From Radionecrosis After Stereotactic Radiation Therapy for Brain Metastases With Machine Learning and Radiomics.

Purpose: Treatment effect or radiation necrosis after stereotactic radiosurgery (SRS) for brain metastases is a common phenomenon often indistinguishable from true progression. Radiomics is an emerging field that promises to improve on conventional imaging. In this study, we sought to apply a radiomics-based prediction model to the problem of diagnosing treatment effect after SRS.

Thirty-eight-negative kinase 1 mediates trauma-induced intestinal injury and multi-organ failure.

Dysregulated intestinal epithelial apoptosis initiates gut injury, alters the intestinal barrier, and can facilitate bacterial translocation leading to a systemic inflammatory response syndrome (SIRS) and/or multi-organ dysfunction syndrome (MODS). A variety of gastrointestinal disorders, including inflammatory bowel disease, have been linked to intestinal apoptosis. Similarly, intestinal hyperpermeability and gut failure occur in critically ill patients, putting the gut at the center of SIRS pathology.

A toolbox for multiplexed super-resolution imaging of the E. coli nucleoid and membrane using novel PAINT labels.

Maintenance of the bacterial homeostasis initially emanates from interactions between proteins and the bacterial nucleoid. Investigating their spatial correlation requires high spatial resolution, especially in tiny, highly confined and crowded bacterial cells. Here, we present super-resolution microscopy using a palette of fluorescent labels that bind transiently to either the membrane or the nucleoid of fixed E.

Survival and Functional Status After Bridge-to-Transplant with a Left Ventricular Assist Device.

The use left ventricular assist devices (LVAD) as a bridge-to-transplant (BTT) has become a common modality to treat end-stage heart failure. We sought to examine the impact of BTT on long-term survival and quality of life after heart transplant. The population was all adult patients undergoing isolated heart transplantation in the United States between 2007 and 2017.

BRAF inhibition causes resilience of melanoma cell lines by inducing the secretion of FGF1.

Approximately half of all melanoma patients harbour activating mutations in the serine/threonine kinase BRAF. This is the basis for one of the main treatment strategies for this tumor type, the targeted therapy with BRAF and MEK inhibitors. While the initial responsiveness to these drugs is high, resistance develops after several months, frequently at sites of the previously responding tumor.

Sucrose Abstinence and Environmental Enrichment Effects on Mesocorticolimbic DARPP32 in Rats.

Dopamine- and cAMP-regulated neuronal phosphoprotein 32 kDa (DARPP32) is a signaling molecule that could serve as a molecular switch, promoting or restraining sucrose seeking. We measured DARPP32 and pThr34 DARPP32 in the brains of male Long-Evans rats with a history of sucrose self-administration followed by 1 or 30 days of abstinence and exposure to either overnight (acute) or one month (chronic) environmental enrichment (EE). Brains were extracted following a 1 h cue reactivity test or no exposure to the test environment.

Cell-Specific Chemical Delivery Using a Selective Nitroreductase-Nitroaryl Pair.

The utility of small molecules to probe or perturb biological systems is limited by the lack of cell-specificity. "Masking" the activity of small molecules using a general chemical modification and "unmasking" it only within target cells overcomes this limitation. To this end, we have developed a selective enzyme-substrate pair consisting of engineered variants of E.

Optimization of fluorophores for chemical tagging and immunohistochemistry of Drosophila neurons.

The use of genetically encoded 'self-labeling tags' with chemical fluorophore ligands enables rapid labeling of specific cells in neural tissue. To improve the chemical tagging of neurons, we synthesized and evaluated new fluorophore ligands based on Cy, Janelia Fluor, Alexa Fluor, and ATTO dyes and tested these with recently improved Drosophila melanogaster transgenes. We found that tissue clearing and mounting in DPX substantially improves signal quality when combined with specific non-cyanine fluorophores.