Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Cats With Hypertrophic Cardiomyopathy.

Objective: To assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR) for cardiac death in cats with hypertrophic cardiomyopathy. Study Design: Prospective observation study. Animals: Ninety-six client-owned cats. Methods: Complete blood count samples were collected from 38 healthy and 58 cats with hypertrophic cardiomyopathy (HCM), and the NLR ratios were analyzed. All cats had echocardiographic measurements performed on the same day as blood collection. Spearman rank correlation was used to assess the relationship between echocardiographic measurements and NLR. Long-term outcome data were obtained, and time to cardiac death and variables associated with cardiac death were analyzed using Kaplan-Meier survival curves and Cox proportional hazards models, respectively. Results: The NLR was significantly higher in cats with confirmed congestive heart failure. When evaluating HCM patients, cats in the third NLR tertile had a significantly higher risk of cardiac death with a hazard ratio of 10.26 (95% CI: 1.84-57.14; p = 0.0001) when compared with that of patients in the first tertile. NLR was significantly associated with echocardiographic measures of left atrial size, left auricular function, the presence of left atrial spontaneous echo contrast (SEC), and thrombus formation. Conclusions and Clinical Relevance: Increased NLR is a negative prognostic indicator in cats with HCM.

Cultural Change Reduces Gender Differences in Mobility and Spatial Ability among Seminomadic Pastoralist-Forager Children in Northern Namibia.

A fundamental cognitive function found across a wide range of species and necessary for survival is the ability to navigate complex environments. It has been suggested that mobility may play an important role in the development of spatial skills. Despite evolutionary arguments offering logical explanations for why sex/gender differences in spatial abilities and mobility might exist, thus far there has been limited sampling from nonindustrialized and subsistence-based societies. This lack of sampling diversity has left many unanswered questions regarding the effects that environmental variation and cultural norms may have in shaping mobility patterns during childhood and the development of spatial competencies that may be associated with it. Here we examine variation in mobility (through GPS tracking and interviews), performance on large-scale spatial skills (i.e., navigational ability), and performance on small-scale spatial skills (e.g., mental rotation task, Corsi blocks task, and water-level task) among Twa forager/pastoralist children whose daily lives have been dramatically altered since settlement and the introduction of government-funded boarding schools. Unlike in previous findings among Twa adults, boys and girls (N = 88; aged 6-18) show similar patterns of travel on all measures of mobility. We also find no significant differences in spatial task performance by gender for large- or small-scale spatial skills. Further, children performed as well as adults did on mental rotation, and they outperformed adults on the water-level task. We discuss how children's early learning environments may influence the development of both large- and small-scale spatial skills.

Cardiac extracellular volume fraction in cats with preclinical hypertrophic cardiomyopathy.

BACKGROUND: Cardiac magnetic resonance imaging (CMR) allows for detection of fibrosis in hypertrophic cardiomyopathy (HCM) by quantification of the extracellular volume fraction (ECV). HYPOTHESIS/OBJECTIVES: To quantify native T1 mapping and ECV in cats. We hypothesize that native T1 mapping and ECV will be significantly increased in HCM cats compared with healthy cats. ANIMALS: Seventeen healthy and 12 preclinical HCM, age-matched, client-owned cats. METHODS: Prospective observational study. Tests performed included indirect blood pressure, CBC, biochemical analysis including total thyroid, urinalysis, transthoracic echocardiogram, and CMR. Cats were considered healthy if all tests were within normal limits and a diagnosis of HCM was determined by the presence of left ventricular concentric hypertrophy ≥6 mm on echocardiography. RESULTS: There were statistically significant differences in LV mass (healthy = 5.87 g, HCM = 10.3 g, P < .0001), native T1 mapping (healthy = 1122 ms, HCM = 1209 ms, P = .004), and ECV (healthy = 26.0%, HCM = 32.6%, P < .0001). Variables of diastolic function including deceleration time of early diastolic transmitral flow (DTE), ratio between peak velocity of early diastolic transmitral flow and peak velocity of late diastolic transmitral flow (E : A), and peak velocity of late diastolic transmitral flow (A wave) were significantly correlated with ECV (DTE; r = 0.73 P = .007, E : A; r = -0.75 P = .004, A wave; r = 0.76 P = .004). CONCLUSIONS AND CLINICAL IMPORTANCE: Quantitative assessment of cardiac ECV is feasible and can provide additional information not available using echocardiography.

Quantitative assessment of left ventricular volume and function by transthoracic and transesophageal echocardiography, ultrasound velocity dilution, and gated magnetic resonance imaging in healthy foals.

OBJECTIVE: To compare measurements of left ventricular volume and function derived from 2-D transthoracic echocardiography (2DE), transesophageal echocardiography (TEE), and the ultrasound velocity dilution cardiac output method (UDCO) with those derived from cardiac MRI (cMRI) in healthy neonatal foals. ANIMALS: 6 healthy 1-week-old Standardbred foals. PROCEDURES: Foals were anesthetized and underwent 2DE, TEE, and cMRI; UDCO was performed simultaneously with 2DE. Images acquired by 2DE included the right parasternal 4-chamber (R4CH), left apical 4- and 2-chamber (biplane), and right parasternal short-axis M-mode (M-mode) views. The longitudinal 4-chamber view was obtained by TEE. Measurements assessed included left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), ejection fraction, stroke volume (LVSV), cardiac output (CO), and cardiac index (CI). Bland-Altman analyses were used to compare measurements derived from biplane, R4CH, and M-mode images and UDCO with cMRI-derived measurements. Repeatability of measurements calculated by 3 independent reviewers was assessed by the intraclass correlation coefficient. RESULTS: Compared with cMRI, all 2DE and TEE modalities underestimated LVEDV and LVESV and overestimated ejection fraction, CO, and CI. The LVSV was underestimated by the biplane, R4CH, and TEE modalities and overestimated by UDCO and M-mode methods. However, the R4CH-derived LVSV, CO, and CI were clinically comparable to cMRI-derived measures. Repeatability was good to excellent for measures derived from the biplane, R4CH, M-mode, UDCO, and cMRI methods and poor for TEE-derived measures. CONCLUSIONS AND CLINICAL RELEVANCE: All assessed modalities yielded clinically acceptable measurements of LVEDV, LVESV, and function, but those measurements should not be used interchangeably when monitoring patient progress.

Cancer therapy-induced cardiomyopathy: can human induced pluripotent stem cell modelling help prevent it?

Cardiotoxic effects from cancer therapy are a major cause of morbidity during cancer treatment. Unexpected toxicity can occur during treatment and/or after completion of therapy, into the time of cancer survivorship. While older drugs such as anthracyclines have well-known cardiotoxic effects, newer drugs such as tyrosine kinase inhibitors, proteasome inhibitors, and immunotherapies also can cause diverse cardiovascular and metabolic complications. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly being used as instruments for disease modelling, drug discovery, and mechanistic toxicity studies. Promising results with hiPSC-CM chemotherapy studies are raising hopes for improving cancer therapies through personalized medicine and safer drug development. Here, we review the cardiotoxicity profiles of common chemotherapeutic agents as well as efforts to model them in vitro using hiPSC-CMs.

Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics.

There is growing interest in using embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) derivatives for tissue regeneration. However, an increased understanding of human immune responses to stem cell-derived allografts is necessary for maintaining long-term graft persistence. To model this alloimmunity, humanized mice engrafted with human hematopoietic and immune cells could prove to be useful. In this study, an in-depth analysis of graft-infiltrating human lymphocytes and splenocytes revealed that humanized mice incompletely model human immune responses toward allogeneic stem cells and their derivatives. Furthermore, using an "allogenized" mouse model, we show the feasibility of reconstituting immunodeficient mice with a functional mouse immune system and describe a key role of innate immune cells in the rejection of mouse stem cell allografts.

Endostatin binds nerve growth factor and thereby inhibits neurite outgrowth and neuronal migration in-vitro.

Endostatin (ES), the C-terminal fragment of collagen XVIII known for its anti-angiogenic properties, is associated with neurological diseases in mammals. In this study, we investigated the effect of ES on nerve growth factor (NGF)-induced neuronal differentiation, migration, neuritogenesis, and neurite extension. ES partially inhibited PC12 cell differentiation and cerebellar granule cell migration. In addition, neurite outgrowth was inhibited in a concentration-dependent manner. This effect was also matrix-dependent, as we observed better inhibition on PC12 cells grown on collagen compared to laminin matrices. Furthermore, we observed partial NGF depletion by collagen and ES, but not by laminin suggesting that NGF-matrix interactions may be important for promoting neuritogenesis, competitive inhibition by ES or low affinity matrix impairs PC12 differentiation and neurite outgrowth. Finally, using a biosensor technique, we demonstrated a direct interaction between NGF and ES suggesting the mechanism of action of ES may involve NGF sequestration. In conclusion, our study demonstrates the inhibitory effect of ES on different steps of neurogenesis including cell differentiation and migration and neuritogenesis by NGF sequestration. Such sequestration may compromise brain repair following injury, but also may play important role in axon finding as well as a potent therapeutical target in diseases involving abnormal elevated neurotrophic growth factor levels. Taken together, this study raises the consideration of ES as a double-edge sword that carries both deleterious and putative therapeutical effects.

Using stereocartography for predicting efficacy of stereoinduction by chiral catalysts.

A computational method called stereocartography is used to examine regions around chiral catalysts that are most stereoinducing during Diels-Alder reactions. Geometries and atomic charges of catalysts are first generated quantum mechanically. The transition state of the reaction being catalyzed is then computed quantum mechanically and those enantiomeric transition states are used as probes to determine where around the catalyst stereoinduction is optimal. A description of how to treat catalysts with multiple conformations is given. In this article seven catalysts containing a variety of ligand motifs and metals were evaluated. The hypothesis that the region of maximum stereoinduction must be spatially coincident with the site of chemistry for a catalyst to be efficient is upheld.

Stereocartography: a computational mapping technique that can locate regions of maximum stereoinduction around chiral catalysts.

A hypothesis concerning asymmetric induction by chiral catalysts is posited, tested, and found to be valid. The hypothesis states that chiral catalysts that are efficient at inducing asymmetry will have their region of maximum stereoinduction spatially congruent with the site of chemistry but inefficient catalysts will not. A simple mapping strategy (stereocartography) is used to assess where the region of maximum stereoinduction is located around a given catalyst. The protocol compares interaction energies between mirror image probes at each point in space around the catalyst being considered. The probes are models of the actual transition states of the reaction being catalyzed by a particular catalyst. The hypothesis was tested on three Diels-Alder reactions. Seventeen of the eighteen catalysts conform to the hypothesis. The idea of using this as a catalyst design tool is presented.