Acute hypernatremia increases functional connectivity of NaCl sensing regions in the human brain: An fMRI pilot study.

Rodent studies demonstrated specialized sodium chloride (NaCl) sensing neurons in the circumventricular organs, which mediate changes in sympathetic nerve activity, arginine vasopressin, thirst, and blood pressure. However, the neural pathways involved in NaCl sensing in the human brain are incompletely understood. The purpose of this pilot study was to determine if acute hypernatremia alters the functional connectivity of NaCl-sensing regions of the brain in healthy young adults.

Effects of a mitochondrial-targeted ubiquinol on vascular function and exercise capacity in chronic kidney disease: a randomized controlled pilot study.

Mitochondria-derived oxidative stress has been implicated in vascular and skeletal muscle abnormalities in chronic kidney disease (CKD). The purpose of this study was to investigate the effects of a mitochondria-targeted ubiquinol (MitoQ) on vascular function and exercise capacity in CKD. In this randomized controlled trial, 18 patients with CKD (means ± SE, age: 62 ± 3 yr and estimated glomerular filtration rate: 45 ± 3 mL/min/1.

Effect of acute handgrip and aerobic exercise on wasted pressure effort and arterial wave reflections in healthy aging.

Aging increases arterial stiffness and wave reflections that augment left ventricular wasted pressure effort (WPE). A single bout of exercise may be effective at acutely reducing WPE via reductions in arterial wave reflections. In young adults (YA) acute aerobic exercise decreases, whereas handgrip increases, wave reflections.

Deep learning based landmark detection for measuring hock and knee angles in sows.

This paper presents a visual deep learning approach to automatically determine hock and knee angles from sow images. Lameness is the second largest reason for culling of breeding herd females and relies on human observers to provide visual scoring for detection which can be slow, subjective, and inconsistent. A deep learning model classified and detected ten and two key body landmarks from the side and rear profile images, respectively (mean average precision = 0.

Inverse salt sensitivity in normotensive adults: role of demographic factors.

Background: Salt sensitivity and inverse salt sensitivity [ISS; a reduction in blood pressure (BP) on a high sodium diet] are each associated with increased incidence of hypertension. The purpose of this analysis was to determine the prevalence of ISS in normotensive adults and whether ISS is associated with any demographic characteristic(s).

Methods: Healthy normotensive, nonobese adults [ n  = 84; 43 women; age = 37 ± 13 years; baseline mean arterial pressure (MAP) = 89 ± 8 mmHg] participated in a controlled feeding study, consuming 7-day low-sodium (20 mmol sodium/day) and high-sodium (300 mmol sodium/day) diets.

Sex differences in microvascular function and arterial hemodynamics in nondialysis chronic kidney disease.

Cardiovascular disease (CVD) is the leading cause of death in chronic kidney disease (CKD). Abnormal arterial hemodynamics contribute to CVD, a relationship that can be mediated by microvascular dysfunction. The purpose of this study was to investigate potential sex differences in arterial hemodynamics and microvascular dysfunction in patients with stages 3 to 4 CKD.

Dietary sodium and health: How much is too much for those with orthostatic disorders?

High dietary salt (NaCl) increases blood pressure (BP) and can adversely impact multiple target organs including the vasculature, heart, kidneys, brain, autonomic nervous system, skin, eyes, and bone. However, patients with orthostatic disorders are told to increase their NaCl intake to help alleviate symptoms. While there is evidence to support the short-term benefits of increasing NaCl intake in these patients, there are few studies assessing the benefits and side effects of long-term high dietary NaCl.

Lower-body dynamic exercise reduces wave reflection in healthy young adults.

New Findings: What is the central question of this study? There is a paradoxical reduction in augmentation index during lower-body dynamic (LBD) exercise in the face of an increase in central pressure. To determine causality, the amplitudes of forward and backward pressure waves were assessed separately using wave separation analysis. What is the main finding and its importance? Reflection magnitude decreased during LBD exercise in healthy young adults and was attributable to an increased forward pressure wave amplitude and decreased backward pressure wave amplitude.

Pulsatile load and wasted pressure effort are reduced following an acute bout of aerobic exercise.

Following aerobic exercise, sustained vasodilation and concomitant reductions in total peripheral resistance (TPR) result in a reduction in blood pressure that is maintained for two or more hours. However, the time course for postexercise changes in reflected wave amplitude and other indices of pulsatile load on the left ventricle have not been thoroughly described. Therefore, we tested the hypothesis that reflected wave amplitude is reduced beyond an hour after cycling at 60% V̇o for 60 min.

Personalized physiologic flow waveforms improve wave reflection estimates compared to triangular flow waveforms in adults.

Central aortic pressure waveforms contain valuable prognostic information in addition to central systolic pressure. Using pressure-flow relations, wave separation analysis can be used to decompose aortic pressure waveforms into forward- (Pf) and backward-traveling (Pb) components. Reflection magnitude, the ratio of pressure amplitudes (RM = Pb/Pf), is a predictor of heart failure and all-cause mortality.

A randomized trial of aerobic exercise in chronic kidney disease: Evidence for blunted cardiopulmonary adaptations.

Background: Patients with chronic kidney disease have reduced cardiorespiratory fitness levels that contribute to mortality.

Objectives: The purpose of this study was to investigate the effects of aerobic exercise on cardiopulmonary function in patients with chronic kidney disease.

Methods: A total of 36 patients (mean [SD] estimated glomerular filtration rate 44 [12] ml/min/1.

The effect of dietary nitrate on exercise capacity in chronic kidney disease: a randomized controlled pilot study.

Background: Chronic Kidney Disease (CKD) patients exhibit a reduced exercise capacity that impacts quality of life. Dietary nitrate supplementation has been shown to have favorable effects on exercise capacity in disease populations by reducing the oxygen cost of exercise. This study investigated whether dietary nitrates would acutely improve exercise capacity in CKD patients.

Dynamic and isometric handgrip exercise increases wave reflection in healthy young adults.

Early return and increased magnitude of wave reflection augments pulsatile load, wastes left ventricular effort, and is associated with cardiovascular events. Acute handgrip (HG) exercise increases surrogate measures of wave reflection such as augmentation index. However, augmentation index does not allow distinguishing between timing versus magnitude of wave reflection and is affected by factors other than wave reflection per se.

Quantitation of Gait and Stance Alterations Due to Monosodium Iodoacetate-induced Knee Osteoarthritis in Yucatan Swine.

Knee osteoarthritis is one of the most common causes of chronic pain worldwide, and several animal models have been developed to investigate disease mechanisms and treatments to combat associated morbidities. Here we describe a novel method for assessment of locomotor pain behavior in Yucatan swine. We used monosodium iodoacetate (MIA) to induce osteoarthritis in the hindlimb knee, and then conducted live observation, quantitative gait analysis, and quantitative weight-bearing stance analysis.

Effects of aerobic exercise on vascular function in nondialysis chronic kidney disease: a randomized controlled trial.

Endothelial dysfunction and arterial stiffness are nontraditional risk factors of chronic kidney disease (CKD)-related cardiovascular disease (CVD) that could be targeted with exercise. This study investigated the effect of moderate to vigorous aerobic exercise on vascular function in nondialysis CKD. In this randomized, controlled trial, 36 nondialysis patients with CKD (means ± SE, age: 58 ± 2 yr, estimated glomerular filtration rate: 44 ± 2 ml·min·1.

Objective evaluation of female feet and leg joint conformation at time of selection and post first parity in swine1.

Feet and legs of replacement females were objectively evaluated at selection, i.e., approximately 150 d of age (n = 319) and post first parity, i.

Cardiopulmonary exercise testing reveals subclinical abnormalities in chronic kidney disease.

Background Reductions in exercise capacity associated with exercise intolerance augment cardiovascular disease risk and predict mortality in chronic kidney disease. This study utilized cardiopulmonary exercise testing to (a) investigate mechanisms of exercise intolerance; (b) unmask subclinical abnormalities that may precede cardiovascular disease in chronic kidney disease. Design The design of this study was cross-sectional.

Design, Synthesis, and Cytotoxic Evaluation of Novel Tubulysin Analogues as ADC Payloads.

The tubulysin class of natural products has attracted much attention from the medicinal chemistry community due to its potent cytotoxicity against a wide range of human cancer cell lines, including significant activity in multidrug-resistant carcinoma models. As a result of their potency, the tubulysins have become an important tool for use in targeted therapy, being widely pursued as payloads in the development of novel small molecule drug conjugates (SMDCs) and antibody-drug conjugates (ADCs). A structure-based and parallel medicinal chemistry approach was applied to the synthesis of novel tubulysin analogues.

Optimization of Tubulysin Antibody-Drug Conjugates: A Case Study in Addressing ADC Metabolism.

As part of our efforts to develop new classes of tubulin inhibitor payloads for antibody-drug conjugate (ADC) programs, we developed a tubulysin ADC that demonstrated excellent in vitro activity but suffered from rapid metabolism of a critical acetate ester. A two-pronged strategy was employed to address this metabolism. First, the hydrolytically labile ester was replaced by a carbamate functional group resulting in a more stable ADC that retained potency in cellular assays.

Evaluation of the thin agar layer method for the recovery of pressure-injured and heat-injured Listeria monocytogenes.

A sublethally injured bacterial cell has been defined as a cell that survives a stress such as heating, freezing, acid treatment, or other antimicrobial intervention but can repair the cellular damage exerted by the stressor and later regain its original ability to grow. Consequently, sublethally injured cells are not likely to be included in conventional enumeration procedures, which could result in unrealistically low counts unless efforts are made to encourage recovery of the injured cells before enumeration. The objective of this study was to evaluate the use of the thin agar layer (TAL) method for the recovery of pressure-injured and heat-injured Listeria monocytogenes in a tryptic soy broth with 0.

Benzimidazole- and indole-substituted 1,3'-bipyrrolidine benzamides as histamine H3 receptor antagonists.

Using a focused screen of biogenic amine compounds we identified a novel series of H(3)R antagonists. A preliminary SAR study led to reduction of MW while increasing binding affinity and potency. Optimization of the physical properties of the series led to (S)-6n, with improved brain to plasma exposure and efficacy in both water intake and novel object recognition models.

A fluorescent assay suitable for inhibitor screening and vanin tissue quantification.

Vanin-1 is a pantetheinase that catalyzes the hydrolysis of pantetheine to produce pantothenic acid (vitamin B5) and cysteamine. Reported here is a highly sensitive fluorescent assay using a novel fluorescently labeled pantothenate derivative. The assay has been used for characterization of a soluble version of human vanin-1 recombinant protein, identification and characterization of hits from high-throughput screening (HTS), and quantification of vanin pantothenase activity in cell lines and tissues.