Reverse Myocardial Remodeling in Hypertrophic Cardiomyopathy: Little Explored Benefit of Exercise

International Journal of Exercise Science 14(2): 1018-1026, 2021. Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease that causes myocardial remodeling. Physical exercise (PE) is a therapeutic resource used in Supervised Cardiac Rehabilitation (SCR) to improve Quality of Life (QL), reducing cardiovascular morbidity and mortality. Therefore, the aim of this study is to report how SCR using a personalized exercise prescription, promoted Reverse Myocardial Remodeling (RMR), improved functionality and QL of a patient with HCM. This is a case report of a 43-year-old sedentary female patient with a Body Mass Index (BMI) of 24.7 kg/m2. The patient was diagnosed with Septal Type Asymmetric HCM. Heart Failure (HF) grade III / IV, according to the New York Heart Association (NYHA), was initially treated with 40mg of Propranolol Hydrochloride twice a day, and presented with excessive fatigue, and angina. The echocardiogram showed a final diastolic volume (FDV) of 130 ml, a final systolic volume (FSV) of 44 ml, a left ventricular mass (LVM) of 236 g, interventricular septum thickness of 14 mm, left ventricular posterior wall (LVPW) thickness of 9 mm, left atrium diameter 46 mm, left ventricular end diastolic diameter of 52mm, septum/left ventricular wall ratio of 1.55 mm, and ejection fraction (EF) of 66% (Teicholz). It was obtained as a result of decreased FDV 130 vs. 102ml, decreased FSV 44 vs. 32 ml, decreased LVM 236 vs. 201 g, increased EF 66 vs. 69%, 26% improvement in QL, and 50% reduction in the dosage of Propranolol Hydrochloride. These results suggest that a personalized SCR program is an adjuvant treatment capable of promoting RMR and improving QL and functionality in a patient with HCM

Restrictions and extensions of semibounded operators

We study restriction and extension theory for semibounded Hermitian operators in the Hardy space of analytic functions on the disk D. Starting with the operator zd/dz, we show that, for every choice of a closed subset F in T=bd(D) of measure zero, there is a densely defined Hermitian restriction of zd/dz corresponding to boundary functions vanishing on F. For every such restriction operator, we classify all its selfadjoint extension, and for each we present a complete spectral picture. We prove that different sets F with the same cardinality can lead to quite different boundary-value problems, inequivalent selfadjoint extension operators, and quite different spectral configurations. As a tool in our analysis, we prove that the von Neumann deficiency spaces, for a fixed set F, have a natural presentation as reproducing kernel Hilbert spaces, with a Hurwitz zeta-function, restricted to FxF, as reproducing kernel.Comment: 63 pages, 11 figure

Influence of spin reorientation on magnetocaloric effect in NdAl2: A microscopic model

We report a theoretical investigation about the influence of the spin reorientation from easy magnetic direction to the applied magnetic field direction on the magnetocaloric properties of NdAl2. This compound was fully investigated using a model Hamiltonian which includes the Zeeman-exchange interactions and the crystalline electrical field, which are responsible for the magnetic anisotropy. All theoretical results were obtained using the proper model parameters for NdAl2, found in the literature. The existence of a minimum in magnetic entropy change below the phase transition was predicted and ascribed to the strong jump on the spin reorientation.74

O Aprendizado Formal de Controladoria e a minimização do Efeito Framing: um estudo de decisões gerenciais envolvendo Custos de Oportunidade

The object of this research was to investigate the impact of the formal learning of Auditing, Accounting and Control in the minimization of cognitive biases in management decisions. For this the experimental scenario together with a situation that involved the concept of the Cost of opportunity was delineated. With the help of this concept, this research seeks to understand the behavior associated with the cognitive bias caused by the framing effect. The experiment counted on a control group where the introduction of biases did not exist in the questions submitted to the respondents, and two experimental groups where the questionnaires had biases, the sample being made up of 115 Accounting and Law undergraduate students of the Federal University of Bahia. For the analysis of the experiment Multiple Logistic Regression was used. The results obtained pointed to the inexistence of contributions to the formal learning of Auditing, Accounting and Control in the reduction of the occurrence of the framing effect.El objetivo de esta pesquisa fue verificar el impacto del aprendizaje formal de Contraloría en la minimización de los sesgos cognoscitivos en decisiones gerenciales. Para eso fue delineado un escenario experimental con situación que involucra el concepto de Costo de oportunidad. Con el auxilio de este concepto, se pretende entender el comportamiento asociado al bies cognitivo provocado por el efecto framing. El experimento contó con un grupo de control, donde no existía la introducción de sesgos en las cuestiones a las cuales los respondientes fueron sometidos, y dos grupos experimentales, donde los cuestionarios contenían los sesgos, siendo la muestra compuesta por 155 estudiantes de los cursos de graduación de Ciencias Contables y Derecho de la Universidad Federal de Bahia. Para el análisis del experimento, fue utilizada la Regresión Logística Múltiple. Los resultados encontrados señalaron la inexistencia de contribuciones del aprendizaje formal de Contraloría en la reducción de la ocurrencia del efecto framing.O objetivo desta pesquisa foi verificar o impacto do Aprendizado Formal de Controladoria na minimização dos vieses cognitivos em decisões gerenciais. Para isso, foi delineado um cenário experimental com situação que envolve o conceito de Custo de Oportunidade. Com o auxílio deste conceito, busca-se entender o comportamento associado ao viés cognitivo provocado pelo Efeito Framing. O experimento contou com um grupo de controle, no qual não existia a introdução de vieses nas questões às quais os respondentes foram submetidos; e dois grupos experimentais, nos quais os questionários continham os vieses, sendo a amostra composta por 155 estudantes dos cursos de graduação de Ciências Contábeis e Direito da Universidade Federal da Bahia (UFBA). Para a análise do experimento, foi utilizada a Regressão Logística Múltipla. Os resultados encontrados apontaram para a inexistência de contribuições do Aprendizado Formal de Controladoria na redução da ocorrência do Efeito Framing

PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis

Patients infected by Leishmania braziliensis develop debilitating skin lesions. The role of inhibitory checkpoint receptors (ICRs) that induce T cell exhaustion during this disease is not known. Transcriptional profiling identified increased expression of ICRs including PD-1, PDL-1, PDL-2, TIM-3, and CTLA-4 in skin lesions of patients that was confirmed by immunohistology where there was increased expression of PD-1, TIM-3, and CTLA-4 in both CD4^{+} and CD8^{+} T cell subsets. Moreover, PDL-1/PDL-2 ligands were increased on skin macrophages compared to healthy controls. The proportions PD1^{+}, but not TIM-3 or CTLA-4 expressing T cells in the circulation were positively correlated with those in the lesions of the same patients, suggesting that PD-1 may regulate T cell function equally in both compartments. Blocking PD-1 signaling in circulating T cells enhanced their proliferative capacity and IFN-γ production, but not TNF-α secretion in response to L. braziliensis recall antigen challenge in vitro. While we previously showed a significant correlation between the accumulation of senescent CD8^{+}CD45RA^{+}CD27^{-} T cells in the circulation and skin lesion size in the patients, there was no such correlation between the extent of PD-1 expression by circulating on T cells and the magnitude of skin lesions suggesting that exhausted-like T cells may not contribute to the cutaneous immunopathology. Nevertheless, we identified exhausted-like T cells in both skin lesions and in the blood. Targeting this population by PD-1 blockade may improve T cell function and thus accelerate parasite clearance that would reduce the cutaneous pathology in cutaneous leishmaniasis

Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology.

Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form

Lessons to be learnt from Leishmania studies

Leishmaniasis is a disease caused by infection with the protozoan parasite Leishmania, which is responsible for three main types of disease: cutaneous leishmaniasis, visceral leishmaniasis and mucocutaneous leishmaniasis based to the site of infection for the particular species. This presents a major challenge to successful drug treatment, as a drug must not only reach antileishmanial concentrations in infected macrophages, the parasites' host cell, but also reach infected cells in locations specific to the type of disease. In this paper we discuss how studies using Leishmania have contributed to our knowledge on how drug delivery systems can be used to improve drug efficacy and delivery

Platelet-activating factor receptor (PAF-R)-dependent pathways control tumour growth and tumour response to chemotherapy

<p>Abstract</p> <p>Background</p> <p>Phagocytosis of apoptotic cells by macrophages induces a suppressor phenotype. Previous data from our group suggested that this occurs via Platelet-activating factor receptor (PAF-R)-mediated pathways. In the present study, we investigated the impact of apoptotic cell inoculation or induction by a chemotherapeutic agent (dacarbazine, DTIC) on tumour growth, microenvironmental parameters and survival, and the effect of treatment with a PAF-R antagonist (WEB2170). These studies were performed in murine tumours: Ehrlich Ascitis Tumour (EAT) and B16F10 melanoma.</p> <p>Methods</p> <p>Tumour growth was assessed by direct counting of EAT cells in the ascitis or by measuring the volume of the solid tumour. Parameters of the tumour microenvironment, such as the frequency of cells expressing cyclo-oxygenase-2 (COX-2), caspase-3 and galectin-3, and microvascular density, were determined by immunohistochemistry. Levels of vascular endothelium growth factor (VEGF) and prostaglandin E2 (PGE2) were determined by ELISA, and levels of nitric oxide (NO) by Griess reaction. PAF-R expression was analysed by immunohistochemistry and flow cytometry.</p> <p>Results</p> <p>Inoculation of apoptotic cells before EAT implantation stimulated tumour growth. This effect was reversed by <it>in vivo </it>pre-treatment with WEB2170. This treatment also reduced tumour growth and modified the microenvironment by reducing PGE2, VEGF and NO production. In B16F10 melanoma, WEB2170 alone or in association with DTIC significantly reduced tumour volume. Survival of the tumour-bearing mice was not affected by WEB2170 treatment but was significantly improved by the combination of DTIC with WEB2170. Tumour microenvironment elements were among the targets of the combination therapy since the relative frequency of COX-2 and galectin-3 positive cells and the microvascular density within the tumour mass were significantly reduced by treatment with WEB2170 or DTIC alone or in combination. Antibodies to PAF-R stained the cells from inside the tumour, but not the tumour cells grown <it>in vitro</it>. At the tissue level, a few cells (probably macrophages) stained positively with antibodies to PAF-R.</p> <p>Conclusions</p> <p>We suggest that PAF-R-dependent pathways are activated during experimental tumour growth, modifying the microenvironment and the phenotype of the tumour macrophages in such a way as to favour tumour growth. Combination therapy with a PAF-R antagonist and a chemotherapeutic drug may represent a new and promising strategy for the treatment of some tumours.</p