Reconfigurable, Transformable Soft Pneumatic Actuator with Tunable Three-Dimensional Deformations for Dexterous Soft Robotics Applications.

Numerous soft actuators based on pneumatic network (PneuNet) design have already been proposed and extensively employed across various soft robotics applications in recent years. Despite their widespread use, a common limitation of most existing designs is that their action is predetermined during the fabrication process, thereby restricting the ability to modify or alter their function during operation. To address this shortcoming, in this article the design of a Reconfigurable, Transformable Soft Pneumatic Actuator (RT-SPA) is proposed.

Asciminib antagonizes transplantable BCR::ABL1-positive lymphoid blast crisis in vivo by targeting malignant stem cells.

Philadelphia chromosome-positive (Ph+) lymphoid blast crisis (BC), emanating from chronic myeloid leukemia (CML), is a fatal disease with limited treatment options. Asciminib (ABL001) is a novel selective allosteric inhibitor of the ABL kinase with high efficacy against TKI-resistant BCR::ABL1. In this study, we demonstrate significant suppression of an aggressive B-lymphoblastic disease and restoration of normal hematopoiesis in an inducible transgenic mouse model of p210-BCR::ABL1-positive CML-BC.

Magnetic resonance spectroscopy in the hippocampus of adult APP/PS1 mice following chronic vitamin D deficiency.

Vitamin D (VitD) deficiency can exacerbate AD progression and may cause changes in brain metabolite levels that can be detected by magnetic resonance spectroscopy (MRS). The purpose of this study was to determine whether chronic VitD deficiency in an AD mouse model caused persistent metabolite levels changes in the hippocampus associated with memory performance. Six-month-old APPSwe/PS1ΔE9 (APP/PS1) mice (N = 14 mice/group) were fed either a VitD deficient (VitD-) diet or a control diet.

Semiautomated pipeline for quantitative analysis of heart histopathology.

Background: Heart diseases are among the leading causes of death worldwide, many of which lead to pathological cardiomyocyte hypertrophy and capillary rarefaction in both patients and animal models, the quantification of which is both technically challenging and highly time-consuming. Here we developed a semiautomated pipeline for quantification of the size of cardiomyocytes and capillary density in cardiac histology, termed HeartJ, by generating macros in ImageJ, a broadly used, open-source, Java-based software.

Methods: We have used modified Gomori silver staining, which is easy to perform and digitize in high throughput, or Fluorescein-labeled lectin staining.

Non-invasive intradialytic percutaneous perfusion monitoring: a view to the heart through the skin.

Introduction: The life-sustaining treatment of hemodialysis (HD) induces recurrent and cumulative systemic circulatory stress resulting in cardiovascular injury. These recurrent insults compound preexisting cardiovascular sequalae leading to the development of myocardial injury and resulting in extremely high morbidity/mortality. This is largely a consequence of challenged microcirculatory flow within the myocardium (evidenced by detailed imaging-based studies).

2,8-Dihydroxyadenine-induced nephropathy causes hexosylceramide accumulation with increased mTOR signaling, reduced levels of protective SirT3 expression and impaired renal mitochondrial function.

Aim: Chronic kidney disease (CKD) is accompanied by increased cardiovascular risk and heart failure (HF). In rodents, 2,8-dihydroxyadenine (DHA)-induced nephropathy is a frequently used CKD model. Cardiac and kidney tubular cells share high energy demand to guarantee constant contractive force of the heart or reabsorption/secretion of primary filtrated molecules and waste products by the kidney.

Hemodialysis-Related Acute Brain Injury Demonstrated by Application of Intradialytic Magnetic Resonance Imaging and Spectroscopy.

Significance Statement: Hemodialysis (HD) results in reduced brain blood flow, and HD-related circulatory stress and regional ischemia are associated with brain injury over time. However, studies to date have not provided definitive direct evidence of acute brain injury during a HD treatment session. Using intradialytic magnetic resonance imaging (MRI) and spectroscopy to examine HD-associated changes in brain structure and neurochemistry, the authors found that multiple white (WM) tracts had diffusion imaging changes characteristic of cytotoxic edema, a consequence of ischemic insult and a precursor to fixed structural WM injury.

Pro-oxidative priming but maintained cardiac function in a broad spectrum of murine models of chronic kidney disease.

Aims: Patients with chronic kidney disease (CKD) have an increased risk of cardiovascular events and exhibit myocardial changes including left ventricular (LV) hypertrophy and fibrosis, overall referred to as 'uremic cardiomyopathy'. Although different CKD animal models have been studied for cardiac effects, lack of consistent reporting on cardiac function and pathology complicates clear comparison of these models. Therefore, this study aimed at a systematic and comprehensive comparison of cardiac function and cardiac pathophysiological characteristics in eight different CKD models and mouse strains, with a main focus on adenine-induced CKD.

Chemokine CCL9 Is Upregulated Early in Chronic Kidney Disease and Counteracts Kidney Inflammation and Fibrosis.

Inflammation and fibrosis play an important pathophysiological role in chronic kidney disease (CKD), with pro-inflammatory mediators and leukocytes promoting organ damage with subsequent fibrosis. Since chemokines are the main regulators of leukocyte chemotaxis and tissue inflammation, we performed systemic chemokine profiling in early CKD in mice. This revealed (C-C motif) ligands 6 and 9 (CCL6 and CCL9) as the most upregulated chemokines, with significantly higher levels of both chemokines in blood (CCL6: 3-4 fold; CCL9: 3-5 fold) as well as kidney as confirmed by Enzyme-linked Immunosorbent Assay (ELISA) in two additional CKD models.

Renal Denervation Prevents Atrial Arrhythmogenic Substrate Development in CKD.

Background: In patients with chronic kidney disease (CKD), atrial fibrillation (AF) is highly prevalent and represents a major risk factor for stroke and death. CKD is associated with atrial proarrhythmic remodeling and activation of the sympathetic nervous system. Whether reduction of the sympathetic nerve activity by renal denervation (RDN) inhibits AF vulnerability in CKD is unknown.

Coagulation-independent effects of thrombin and Factor Xa: role of protease-activated receptors in pulmonary hypertension.

Aims: Pulmonary arterial hypertension (PAH) is a devastating disease with limited therapeutic options. Vascular remodelling of pulmonary arteries, characterized by increased proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), is a hallmark of PAH. Here, we aimed to systematically characterize coagulation-independent effects of key coagulation proteases thrombin and Factor Xa (FXa) and their designated receptors, protease-activated receptor (PAR)-1 and -2, on PASMCs in vitro and experimental PAH in vivo.

Effects of Memantine and High Dose Vitamin D on Gait in Male APP/PS1 Alzheimer's Disease Mice Following Vitamin D Deprivation.

Background: Altered gait is a frequent feature of Alzheimer's disease (AD), as is vitamin D deficiency. Treatment with memantine and vitamin D can protect cortical axons from exposure to amyloid-β and glutamate toxicity, suggesting this combination may mitigate altered gait in AD.

Objective: Investigate the effects of vitamin D deprivation and subsequent treatment with memantine and vitamin D enrichment on gait performance in APPswe/PS1dE9 mice.

Disrupted PI3K subunit p110α signaling protects against pulmonary hypertension and reverses established disease in rodents.

Enhanced signaling via RTKs in pulmonary hypertension (PH) impedes current treatment options because it perpetuates proliferation and apoptosis resistance of pulmonary arterial smooth muscle cells (PASMCs). Here, we demonstrated hyperphosphorylation of multiple RTKs in diseased human vessels and increased activation of their common downstream effector phosphatidylinositol 3'-kinase (PI3K), which thus emerged as an attractive therapeutic target. Systematic characterization of class IA catalytic PI3K isoforms identified p110α as the key regulator of pathogenic signaling pathways and PASMC responses (proliferation, migration, survival) downstream of multiple RTKs.

Multisystemic Cellular Tropism of SARS-CoV-2 in Autopsies of COVID-19 Patients.

Multiorgan tropism of SARS-CoV-2 has previously been shown for several major organs. We have comprehensively analyzed 25 different formalin-fixed paraffin-embedded (FFPE) tissues/organs from autopsies of fatal COVID-19 cases ( = 8), using histopathological assessment, detection of SARS-CoV-2 RNA using polymerase chain reaction and RNA in situ hybridization, viral protein using immunohistochemistry, and virus particles using transmission electron microscopy. SARS-CoV-2 RNA was mainly localized in epithelial cells across all organs.

SARS-CoV-2 RNA screening in routine pathology specimens.

Virus detection methods are important to cope with the SARS-CoV-2 pandemics. Apart from the lung, SARS-CoV-2 was detected in multiple organs in severe cases. Less is known on organ tropism in patients developing mild or no symptoms, and some of such patients might be missed in symptom-indicated swab testing.

Effect of Memantine Treatment and Combination with Vitamin D Supplementation on Body Composition in the APP/PS1 Mouse Model of Alzheimer's Disease Following Chronic Vitamin D Deficiency.

Background: Vitamin D deficiency and altered body composition are common in Alzheimer's disease (AD). Memantine with vitamin D supplementation can protect cortical axons against amyloid-β exposure and glutamate toxicity.

Objective: To study the effects of vitamin D deprivation and subsequent treatment with memantine and vitamin D enrichment on whole-body composition using a mouse model of AD.

Repeated exposure to transient obstructive sleep apnea-related conditions causes an atrial fibrillation substrate in a chronic rat model.

Background: High night-to-night variability in obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF). Obstructive apneas are characterized by intermittent deoxygenation-reoxygenation and intrathoracic pressure swings during ineffective inspiration against occluded upper airways.

Objective: We elucidated the effect of repeated exposure to transient OSA conditions simulated by intermittent negative upper airway pressure (INAP) on the development of an AF substrate.

Glutamate and Dysconnection in the Salience Network: Neurochemical, Effective Connectivity, and Computational Evidence in Schizophrenia.

Background: Functional dysconnection in schizophrenia is underwritten by a pathophysiology of the glutamate neurotransmission that affects the excitation-inhibition balance in key nodes of the salience network. Physiologically, this manifests as aberrant effective connectivity in intrinsic connections involving inhibitory interneurons. In computational terms, this produces a pathology of evidence accumulation and ensuing inference in the brain.

Reduced Hippocampal Glutamate and Posterior Cingulate N-Acetyl Aspartate in Mild Cognitive Impairment and Alzheimer's Disease Is Associated with Episodic Memory Performance and White Matter Integrity in the Cingulum: A Pilot Study.

Identification of biological changes underlying the early symptoms of Alzheimer's disease (AD) will help to identify and stage individuals prior to symptom onset. The limbic system, which supports episodic memory and is impaired early in AD, is a primary target. In this study, brain metabolism and microstructure evaluated by high field (7 Tesla) proton magnetic resonance spectroscopy (1H-MRS) and diffusion tensor imaging (DTI) were evaluated in the limbic system of eight individuals with mild cognitive impairment (MCI), nine with AD, and sixteen normal elderly controls (NEC).

New technique to reduce systemic side effects of timolol eye drops: The tissue press method-Cross-over clinical trial.

Importance: Nasolacrimal occlusion (NLO) is effective in reducing systemic absorption of eye drop medication but it is difficult and often performed poorly. We propose an alternative easier and equally effective technique.

Background: To test the effectiveness of systemic absorption, we evaluated plasma concentration and ocular effects after topically administered timolol and compared to NLO.

Evolving complexity of MIF signaling.

Macrophage migration inhibitory factor (MIF) is a cytokine expressed in various cell types, including hematopoietic, epithelial, endothelial, mesenchymal and neuronal cells. Altered MIF expression has been associated with a multitude of diseases ranging from inflammatory disorders like sepsis, lupus and rheumatoid arthritis to organ pathologies such as heart failure, myocardial infarction, acute kidney injury, organ fibrosis and a number of malignancies. The implication of MIF in these diseases was supported by numerous animal studies.

1H MR spectroscopy of the motor cortex immediately following transcranial direct current stimulation at 7 Tesla.

Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that may modulate cortical excitability, metabolite concentration, and human behaviour. The supplementary motor area (SMA) has been largely ignored as a potential target for tDCS neurorehabilitation but is an important region in motor compensation after brain injury with strong efferent connections to the primary motor cortex (M1). The objective of this work was to measure tissue metabolite changes in the human motor cortex immediately following tDCS.

Optimized in vivo brain glutamate measurement using long-echo-time semi-LASER at 7 T.

A short echo time (T ) is commonly used for brain glutamate measurement by H MRS to minimize drawbacks of long T such as signal modulation due to J evolution and T relaxation. However, J coupling causes the spectral patterns of glutamate to change with T , and the shortest achievable T may not produce the optimal glutamate measurement. The purpose of this study was to determine the optimal T for glutamate measurement at 7 T using semi-LASER (localization by adiabatic selective refocusing).

Activated renal tubular Wnt/β-catenin signaling triggers renal inflammation during overload proteinuria.

Imbalance of Wnt/β-catenin signaling in renal cells is associated with renal dysfunction, yet the precise mechanism is poorly understood. Previously we observed activated Wnt/β-catenin signaling in renal tubules during proteinuric nephropathy with an unknown net effect. Therefore, to identify the definitive role of tubular Wnt/β-catenin, we generated a novel transgenic "Tubcat" mouse conditionally expressing stabilized β-catenin specifically in renal tubules following tamoxifen administration.