Effect of an NHE3 inhibitor in combination with an NPT2b inhibitor on gastrointestinal phosphate absorption in Rodent models.

Many of the pathological consequences of chronic kidney disease can be attributed to an elevation in serum phosphate levels. Current therapies focused on decreasing intestinal phosphate absorption to treat hyperphosphatemia are inadequate. The most effective therapeutic strategy may be to target multiple absorptive pathways.

Development of a long-acting relaxin analogue, LY3540378, for treatment of chronic heart failure.

Background And Purpose: Chronic heart failure, a progressive disease with limited treatment options currently available, especially in heart failure with preserved ejection fraction (HFpEF), represents an unmet medical need as well as an economic burden. The development of a novel therapeutic to slow or reverse disease progression would be highly impactful to patients and society. Relaxin-2 (relaxin) is a human hormone regulating cardiovascular, renal, and pulmonary adaptations during pregnancy.

COVID-19 presenting after Elective Off-pump Coronary Artery Bypass Grafting and Lessons Learned.

Background: Cases of COVID-19 presenting after elective cardiac surgery are rare. Published literature suggests that such cases have a high morbidity and mortality rate. Here, we report a case of COVID-19 presenting after an elective, isolated off-pump coronary artery bypass (OPCAB).

How do mobility restrictions and social distancing during COVID-19 affect oil price?

This paper provides an analysis of the effect of the COVID-19 outbreak on the crude oil price. Using a newly developed air mobility index and Apple's driving trends index, we assess the effect of human mobility restrictions and social distancing during the COVID-19 pandemic on the crude oil price. We apply a quantile regression model, which evaluates different quantiles of the crude oil price.

Effects of pharmacological inhibition of the sodium-dependent phosphate cotransporter 2b (NPT2b) on intestinal phosphate absorption in mouse and rat models.

An excess phosphate burden in renal disease has pathological consequences for bone, kidney, and heart. Therapies to decrease intestinal phosphate absorption have been used to address the problem, but with limited success. Here, we describe the in vivo effects of a novel potent inhibitor of the intestinal sodium-dependent phosphate cotransporter NPT2b, LY3358966.

Impacts of COVID-19 local spread and Google search trend on the US stock market.

We develop a novel temporal complex network approach to quantify the US county level spread dynamics of COVID-19. We use both conventional econometric and Machine Learning (ML) models that incorporate the local spread dynamics, COVID-19 cases and death, and Google search activities to assess if incorporating information about local spreads improves the predictive accuracy of models for the US stock market. The results suggest that COVID-19 cases and deaths, its local spread, and Google searches have impacts on abnormal stock prices between January 2020 to May 2020.

Topological clustering of multilayer networks.

Multilayer networks continue to gain significant attention in many areas of study, particularly due to their high utility in modeling interdependent systems such as critical infrastructures, human brain connectome, and socioenvironmental ecosystems. However, clustering of multilayer networks, especially using the information on higher-order interactions of the system entities, still remains in its infancy. In turn, higher-order connectivity is often the key in such multilayer network applications as developing optimal partitioning of critical infrastructures in order to isolate unhealthy system components under cyber-physical threats and simultaneous identification of multiple brain regions affected by trauma or mental illness.

Selective Phosphodiesterase 1 Inhibitor BTTQ Reduces Blood Pressure in Spontaneously Hypertensive and Dahl Salt Sensitive Rats: Role of Peripheral Vasodilation.

Regulation of the peripheral vascular resistance via modulating the vessel diameter has been considered as a main determinant of the arterial blood pressure. Phosphodiesterase enzymes (PDE1-11) hydrolyse cyclic nucleotides, which are key players controlling the vessel diameter and, thus, peripheral resistance. Here, we have tested and reported the effects of a novel selective PDE1 inhibitor (BTTQ) on the cardiovascular system.

What network motifs tell us about resilience and reliability of complex networks.

Network motifs are often called the building blocks of networks. Analysis of motifs has been found to be an indispensable tool for understanding local network structure, in contrast to measures based on node degree distribution and its functions that primarily address a global network topology. As a result, networks that are similar in terms of global topological properties may differ noticeably at a local level.

Identification of 4-Aminopyrazolopyrimidine Metabolite That May Contribute to the Hypolipidemic Effects of LY2584702 in Long Evans Diet-Induced Obese Rats.

LY2584702 is an inhibitor of p70 S6 kinase-1 previously developed for the treatment of cancer. In two phase 1 trials in oncology patients, significant reductions of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride were observed. In the current study, we sought to understand the potential mechanism of action of this compound in regulating lipid metabolism.

Rare association of retinitis pigmentosa and Marfan's syndrome--a case report.

A 25 years old male patient presented with long stature with disproportionately long limbs and digits (arachnodactyly). Examination of cardiovascular system showed mitral regurgitation and dilatation of aortic root. Slit lamp examination showed bilateral superotemporal dislocation of lens.

Ocular manifestations in children with cerebral palsy.

To evaluate the prevalence of ocular abnormalities among children with cerebral palsy, 140 patients with age between 6 months and 16 years were selected and the overall incidence of ocular abnormalities in this study was 42.1%. Two major ocular abnormalities identified in these cases were strabismus in 36.

Sustained hemodynamic stress disrupts normal circadian rhythms in calcineurin-dependent signaling and protein phosphorylation in the heart.

Rationale: Despite overwhelming evidence of the importance of circadian rhythms in cardiovascular health and disease, little is known regarding the circadian regulation of intracellular signaling pathways controlling cardiac function and remodeling.

Objective: To assess circadian changes in processes dependent on the protein phosphatase calcineurin, relative to changes in phosphorylation of cardiac proteins, in normal, hypertrophic, and failing hearts.

Methods And Results: We found evidence of large circadian oscillations in calcineurin-dependent activities in the left ventricle of healthy C57BL/6 mice.

The CCAAT/enhancer binding protein beta (C/EBPbeta) cooperates with NFAT to control expression of the calcineurin regulatory protein RCAN1-4.

Regulator of calcineurin 1 (RCAN1) inhibits the protein phosphatase calcineurin and is required for appropriate immune responses, synaptic plasticity, vascular tone, angiogenesis, and cardiac remodeling. Expression of the RCAN1-4 isoform is under the control of the calcineurin-responsive transcription factor NFAT. Typically, NFATs act in cooperation with other transcription factors to achieve maximal activation of gene expression.

A prospective evaluation of anterior chamber contamination following cataract surgery.

Anterior chamber aspirate cultures were done in 57 patients who underwent uncomplicated manual small incision cataract surgery with posterior chamber intra-ocular lens implantation. The aspirates were collected at the time of wound closures. The specimens were immediately inoculated into blood agar, chocolate agar and thioglycolate broth.

The Down syndrome critical region protein RCAN1 regulates long-term potentiation and memory via inhibition of phosphatase signaling.

Regulator of calcineurin 1 (RCAN1/MCIP1/DSCR1) regulates the calmodulin-dependent phosphatase calcineurin. Because it is located on human chromosome 21, RCAN1 has been postulated to contribute to mental retardation in Down syndrome and has been reported to be associated with neuronal degeneration in Alzheimer's disease. The studies herein are the first to assess the role of RCAN1 in memory and synaptic plasticity by examining the behavioral and electrophysiological properties of RCAN1 knock-out mice.

Klippel-Feil syndrome: a case report and current understanding of molecular genetic background.

A case of Klippel-Feil syndrome in a 12-year-old boy presentingwith the features of low set posterior hairline, short webbed neck, scoliosis and Sprengel's deformity associated with upper eyelid coloboma and pre-auricular appendages is described. Radiologically there was evidence of maldeveloped cervical and upper thoracic vertebrae associated with elevated scapula. The association of the eyelid defect and pre-auricular appendages has not been documented in the past.

Foxo transcription factors blunt cardiac hypertrophy by inhibiting calcineurin signaling.

Background: Cellular hypertrophy requires coordinated regulation of progrowth and antigrowth mechanisms. In cultured neonatal cardiomyocytes, Foxo transcription factors trigger an atrophy-related gene program that counters hypertrophic growth. However, downstream molecular events are not yet well defined.

Unraveling the temporal pattern of diet-induced insulin resistance in individual organs and cardiac dysfunction in C57BL/6 mice.

Type 2 diabetes is a heterogeneous disease characterized by insulin resistance and altered glucose and lipid metabolism in multiple organs. To understand the complex series of events that occur during the development of obesity-associated diabetes, we examined the temporal pattern of changes in insulin action and glucose metabolism in individual organs during chronic high-fat feeding in C57BL/6 mice. Insulin-stimulated cardiac glucose metabolism was significantly reduced after 1.

Differential activation of stress-response signaling in load-induced cardiac hypertrophy and failure.

Hypertrophic growth of the myocardium occurs in most forms of heart failure and may contribute to the pathogenesis of the failure state. Little is known about the regulatory mechanisms governing the often-coexisting phenotypes of hypertrophy, systolic failure, and diastolic stiffness that characterize clinical disease. We hypothesized that intracellular signaling pathways are differentially activated by graded degrees of hemodynamic stress.

Nosocomial ocular infection--a prospective study.

Nosocomial infection of the eye is an uncommon complication, acquired during the course of hospital management. It may prolong the disease process or even destroy the eye. The overall incidence varies considerably by hospital services.