A randomized controlled trial of the effect of spironolactone on left ventricular mass in hemodialysis patients

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Sympathetic stimulation with norepinephrine may come at a cost

<正>Norepinephrine (NE; also known as noradrenaline) is the body's primary adrenergic neurotransmitter which belongs to the catecholamine family. Norepinephrine has pharmacologic effects on theα1 (Suita et al.,2015),α2 (Schwartz,1997),β1,β2 andβ3(Tsukada et al., 2003) adrenoceptors. In the brain, norepinephrine increases arousal and alertness, promotes vigilance, enhances formation and retrieval of memory, and focuses attention. It also increases restlessness and anxiety. In the remainder of the body,     

Increasing Rate of Noninterventional Treatment Management in Localized Prostate Cancer Candidates for Active Surveillance: A North American Population-Based Study

Background

The rate of noninterventional treatment (NIT) in prostate cancer (PCa) active surveillance (AS) candidates is on the rise. However, contemporary data are unavailable. We described community-based NIT rates within 16 Surveillance Epidemiology and End Results (SEER) registries between 2010 and 2014.

ZIKAVID—Zika virus infection database: a new platform to analyze the molecular impact of Zika virus infection

The recent outbreak of Zika virus (ZIKV) in Brazil and other countries globally demonstrated the relevance of ZIKV studies. During and after this outbreak, there was an intense increase in scientific production on ZIKV infections, especially toward alterations promoted by the infection and related to clinical outcomes. Considering this massive amount of new data, mainly thousands of genes and proteins whose expression is impacted by ZIKV infection, the ZIKA Virus Infection Database (ZIKAVID) was created. ZIKAVID is an online database that comprises all genes or proteins, and associated information, for which expression was experimentally measured and found to be altered after ZIKV infection. The database, available at https://zikavid.org, contains 16,984 entries of gene expression measurements from a total of 7348 genes. It allows users to easily perform searches for different experimental hosts (cell lines, tissues, and animal models), ZIKV strains (African, Asian, and Brazilian), and target molecules (messenger RNA [mRNA] and protein), among others, used in differential expression studies regarding ZIKV infection. In this way, the ZIKAVID will serve as an additional and important resource to improve the characterization of the molecular impact and pathogenesis associated with ZIKV infection.     

Immunomodulatory treatment for mucosa-associated lymphoid tissue lymphoma (MALT lymphoma)

The pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphoma has been characterized as a dynamic process driven by lymphoma cell dependency on T-cell signaling, chronic antigenic stimulation of marginal zone B-cells and activation of the nuclear factor-kappa B signaling pathway. This concept is underlined by the strong causal connection of chronic Helicobacter pylori associated gastritis and MALT lymphoma development based on perpetual auto-antigenic stimulation of Helicobacter pylori-specific T-cells, but also its association with further potential infectious triggers and autoimmune disorders for extragastric lymphoma sites. Thus, given the dependency of MALT lymphoma cells on the tumor microenvironment, this specific entity appears highly suitable for immunomodulatory treatment strategies. Several approaches have been assessed in the last years including promising data on immunomodulatory agents “IMiDs” thalidomide and lenalidomide, macrolide antibiotics and antibodies. The aim of the present review is to discuss rationales for immunomodulatory therapies in MALT lymphoma and to present the statu quo on immunomodulatory and therefore chemotherapy-free treatment strategies for these patients.     

Motion‐compensated b‐tensor encoding for in vivo cardiac diffusion‐weighted imaging

Motion is a major confound in diffusion‐weighted imaging (DWI) in the body, and it is a common cause of image artefacts. The effects are particularly severe in cardiac applications, due to the nonrigid cyclical deformation of the myocardium. Spin echo‐based DWI commonly employs gradient moment‐nulling techniques to desensitise the acquisition to velocity and acceleration, ie, nulling gradient moments up to the 2nd order (M2‐nulled). However, current M2‐nulled DWI scans are limited to encode diffusion along a single direction at a time. We propose a method for designing b‐tensors of arbitrary shapes, including planar, spherical, prolate and oblate tensors, while nulling gradient moments up to the 2nd order and beyond. The design strategy comprises initialising the diffusion encoding gradients in two encoding blocks about the refocusing pulse, followed by appropriate scaling and rotation, which further enables nulling undesired effects of concomitant gradients. Proof‐of‐concept assessment of in vivo mean diffusivity (MD) was performed using linear and spherical tensor encoding (LTE and STE, respectively) in the hearts of five healthy volunteers. The results of the M2‐nulled STE showed that (a) the sequence was robust to cardiac motion, and (b) MD was higher than that acquired using standard M2‐nulled LTE, where diffusion‐weighting was applied in three orthogonal directions, which may be attributed to the presence of restricted diffusion and microscopic diffusion anisotropy. Provided adequate signal‐to‐noise ratio, STE could significantly shorten estimation of MD compared with the conventional LTE approach. Importantly, our theoretical analysis and the proposed gradient waveform design may be useful in microstructure imaging beyond diffusion tensor imaging where the effects of motion must be suppressed.     

Intranasal Delivery of Exendin-4 Confers Neuroprotective Effect Against Cerebral Ischemia in Mice

Exendin-4 is now considered as a promising drug for the treatment of cerebral ischemia. To determine the neuroprotective effects of intranasal exendin-4, C57BL/6J mice were intranasally administered with exendin-4 daily for 7 days before middle cerebral artery occlusion (MCAO) surgery. Intranasally administered exendin-4 produced higher brain concentrations and lower plasma concentrations when compared to identical doses administered interperitoneally. Neurological deficits and volume of infarcted lesions were analyzed 24 h after ischemia. Intranasal administration of exendin-4 exhibited significant neuroprotection in C57BL/6 mice subjected to MCAO by reducing neurological deficit scores and infarct volume. The neuroprotective effects of exendin-4 were blocked by the knockdown of GLP-1R with shRNA. However, exendin-4 has no impact on glucose and insulin levels which indicated that the neuroprotective effect was mediated by the activation of GLP-1R in the brain. Exendin-4 intranasal administration restored the balance between pro- and anti-apoptotic proteins and decreased the expression of Caspase-3. The anti-apoptotic effect was mediated by the cAMP/PKA and PI3K/Akt pathway. These findings provided evidence that exendin-4 intranasal administration exerted a neuroprotective effect mediated by an anti-apoptotic mechanism in MCAO mice and protected neurons against ischemic injury through the GLP-1R pathway in the brain. Intranasal delivery of exendin-4 might be a promising strategy for the treatment of ischemic stroke.