Showing papers by "Nova Southeastern University published in 2022"

Role of environmental toxicants in the development of hypertensive and cardiovascular diseases

Abstract: The incidence of hypertension with diabetes mellitus (DM) as a co-morbid condition is on the rise worldwide. In 2000, an estimated 972 million adults had hypertension, which is predicted to grow to 1.56 billion by 2025. Hypertension often leads to diabetes mellitus that strongly puts the patients at an increased risk of cardiovascular, kidney, and/or atherosclerotic diseases. Hypertension has been identified as a major risk factor for the development of diabetes; patients with hypertension are at two-to-three-fold higher risk of developing diabetes than patients with normal blood pressure (BP). Causes for the increase in hypertension and diabetes are not well understood, environmental factors (e.g., exposure to environmental toxicants like heavy metals, organic solvents, pesticides, alcohol, and urban lifestyle) have been postulated as one of the reasons contributing to hypertension and cardiovascular diseases (CVD). The mechanism of action(s) of these toxicants in developing hypertension and CVDs is not well defined. Research studies have linked hypertension with the chronic consumption of alcohol and exposure to metals like lead, mercury, and arsenic have also been linked to hypertension and CVD. Workers chronically exposed to styrene have a higher incidence of CVD. Recent studies have demonstrated that exposure to particulate matter (PM) in diesel exhaust and urban air contributes to increased CVD and mortality. In this review, we have imparted the role of environmental toxicants such as heavy metals, organic pollutants, PM, alcohol, and some drugs in hypertension and CVD along with possible mechanisms and limitations in extrapolating animal data to humans.

Adrenal G Protein-Coupled Receptors and the Failing Heart: A Long-distance, Yet Intimate Affair

Abstract: Systolic heart failure (HF) is a chronic clinical syndrome characterized by the reduction in cardiac function and still remains the disease with the highest mortality worldwide. Despite considerable advances in pharmacological treatment, HF represents a severe clinical and social burden. Chronic human HF is characterized by several important neurohormonal perturbations, emanating from both the autonomic nervous system and the adrenal glands. Circulating catecholamines (norepinephrine and epinephrine) and aldosterone elevations are among the salient alterations that confer significant hormonal burden on the already compromised function of the failing heart. This is why sympatholytic treatments (such as β-blockers) and renin-angiotensin system inhibitors or mineralocorticoid receptor antagonists, which block the effects of angiotensin II (AngII) and aldosterone on the failing heart, are part of the mainstay HF pharmacotherapy presently. The adrenal gland plays an important role in the modulation of cardiac neurohormonal stress because it is the source of almost all aldosterone, of all epinephrine, and of a significant amount of norepinephrine reaching the failing myocardium from the blood circulation. Synthesis and release of these hormones in the adrenals is tightly regulated by adrenal G protein-coupled receptors (GPCRs), such as adrenergic receptors and AngII receptors. In this review, we discuss important aspects of adrenal GPCR signaling and regulation, as they pertain to modulation of cardiac function in the context of chronic HF, by focusing on the 2 best studied adrenal GPCR types in that context, adrenergic receptors and AngII receptors (AT1Rs). Particular emphasis is given to findings from the past decade and a half that highlight the emerging roles of the GPCR-kinases and the β-arrestins in the adrenals, 2 protein families that regulate the signaling and functioning of GPCRs in all tissues, including the myocardium and the adrenal gland.

Double active transient thermography

Abstract: This paper presents an innovative variant of the Active Transient Thermography (ATT), designated Double Active Transient Thermography (DATT), where the component inspected is excited by one heat and one cold sources. The goal is to speed up and improve the temperature contrast, namely for polymer matrix composites parts produced by Additive Manufacturing. Finite element analysis of the thermal phenomena involved in DATT were performed to assist the definition of the experimental set-ups and confirm the high potential of the technique. Experimental results prove that the introduction of the cold flow increases the temperature contrast up to 100%, comparing with ATT, and mid thickness defects are the ones that benefits the most from this technique. Therefore, the improvement of the inspection procedure is achieved by two means: enhancing the thermal contrast of the defects, and/or anticipating the instant when the maximum contrasts occur.

Improvement of Mineral and Bone Disorders After Renal Transplantation

Abstract: Posttransplant mineral and bone diseases are causes of fractures, and their association with cardiovascular events is being studied.We analyzed the evolution of biochemical, histological, and imaging parameters pre- and 1 y post-renal transplantation in 69 patients and correlated mineral and bone findings with coronary calcifications. At inclusion and after 12 mo, clinical data and echocardiographic findings were recorded, and laboratory evaluations, radiography of the pelvis and hands, and bone biopsy were performed. Noncontrast cardiac computed tomography was performed during the second evaluation.Serum levels of fibroblast growth factor 23 and sclerostin decreased in all patients, parathyroid hormone levels decreased in 89.8% of patients, bone alkaline phosphatase levels decreased in 68.1% of patients, and alpha-Klotho levels increased in 65.2% of patients. More than half of the patients presented with renal osteodystrophy at both biopsies, but histological findings improved: a significant transition from high to normal or low turnover and no significant differences in volume, mineralization defect, or cortical porosity at the 2 evaluations. Alpha-Klotho, sclerostin, and bone alkaline phosphatase shifts affect bone changes. Neither echocardiographic findings nor vascular calcification scores differed between the 2 points. Both the pretransplant period (dialysis vintage, sclerostin, and low bone volume at baseline) and the maintenance of abnormalities in the posttransplant period (high turnover posttransplant) were the most reliable predictors of the severity of the coronary calcification percentile.Renal transplantation improved bone and mineral abnormalities. The pretransplant period determines the severity of calcification.

Cholesteryl hemiazelate causes lysosome dysfunction impacting vascular smooth muscle cell homeostasis

Abstract: In atherosclerotic lesions, vascular smooth muscle cells (VSMCs) represent half of the foam cell population, which is characterized by an aberrant accumulation of undigested lipids within lysosomes. Loss of lysosome function impacts VSMC homeostasis and disease progression. Understanding the molecular mechanisms underlying lysosome dysfunction in these cells is, therefore, crucial. We identify cholesteryl hemiazelate (ChA), a stable oxidation end-product of cholesteryl-polyunsaturated fatty acid esters, as an inducer of lysosome malfunction in VSMCs. ChA-treated VSMCs acquire a foam-cell-like phenotype, characterized by enlarged lysosomes full of ChA and neutral lipids. The lysosomes are perinuclear and exhibit degradative capacity and cargo exit defects. Lysosome luminal pH is also altered. Even though the transcriptional response machinery and autophagy are not activated by ChA, the addition of recombinant lysosomal acid lipase (LAL) is able to rescue lysosome dysfunction. ChA significantly affects VSMC proliferation and migration, impacting atherosclerosis. In summary, this work shows that ChA is sufficient to induce lysosomal dysfunction in VSMCs, that, in ChA-treated VSMCs, neither lysosome biogenesis nor autophagy are triggered, and, finally, that recombinant LAL can be a therapeutic approach for lysosomal dysfunction.

The urgent need for new antibiotics

Abstract: We have known for some time that bacteria that were routinely beaten down a decade ago are now getting the upper hand, and that some common bacterial infections now require therapy that combines two or three different antibiotics. And this strategy is not a long-term solution. So, how do we get new antibiotics? That is a complex question, but fortunately, there are some interesting approaches seen in various countries. The reason for the dearth of new antibiotics should be clear to all. They are used for only 7 or 10 days rather infrequently, while drugs for hypertension, diabetes, COPD, asthma, GERD, A-fib, etc. are often used daily for the remainder of the patient’s life. Just as the FDA allows shortcuts in the approval process for orphan drugs, and more recently, for COVID-19 vaccines and treatments, we might consider the same pathway to encourage R&D in the antibiotics area. This includes shorter and less populated clinical trials which are less costly. Another avenue to reduce manufacturing costs is by subsidizing the R&D expense via grants from Ministries of Health, where the government might agree to pay for half or some fixed amount of the drug development cost. Another method to make antibiotic research more attractive is by granting a lengthier period of exclusivity via an extended patent life. Patients could be required to pay an antibiotic encouragement tax that would be almost unnoticeable. If, for example, 25 cents were to be added to the cost of every dispensed prescription, that plan would yield millions of dollars per year to support antibiotic research. It is estimated that bringing a new medication to market requires an investment of over $1 million, but that number can be reduced by patient tax contributions and by government subsidies.

Recent advances in nanoscale targeted therapy of HER2-positive breast cancer

Abstract: Breast cancer is considered as the second major cause of death among women with a high mortality rate worldwide. The exceptionally fast rate of metastasis, the emergence of drug-resistant mechanisms, and the occurrence of inadvertent side effects by cytotoxic chemotherapies often make conventional chemotherapy and immunotherapy treatments ineffective. Similar to other solid tumours, breast cancer can develop unique cellular and molecular characteristics forming an atypical permissive tumour microenvironment (TME). Due to the unique features of TME, cancer cells can further proliferate and coadapt with the stromal cells and evade immunosurveillance. Breast cancer cells aberrantly abundantly express various pieces of molecular machinery (the so-called oncomarkers) in favour of their survival, progression, metastasis, and further invasion. Such overexpressed oncomarkers can be exploited in the detection and targeted therapy of cancer. Among breast cancer oncomarkers, epidermal growth factor receptors, particularly HER2, are considered as clinically valid molecular targets not only for the thorough diagnosis but also for the targeted therapy of the disease using different conventional and advanced nanoscale treatment modalities. This review aims to elaborate on the recent advances in terms of targeted therapy of HER2-positive breast cancer, and discuss various types of multifunctional nanomedicines/theranostics, and antibody-/aptamer-drug conjugates.

Ambidextrous Learning in Buyer-Supplier Relationships: The Role of Strategic and Operational Information Sharing

Abstract: Achieving competitive advantage in a dynamic environment requires firms to exploit their current capabilities and explore new opportunities through innovation. Organizational learning theory refers to these two types of focused learning activities as exploitation and exploration, and jointly as ambidextrous learning. Suppliers can play an important role in the learning process. This research focuses on the role of strategic and operational information sharing between buyers and suppliers in promoting ambidextrous learning. Based on a survey of supply chain managers in U.S. manufacturing firms, the findings indicate that sharing operational information promotes exploitative performance, while sharing strategic information promotes exploratory performance. Both exploitative and exploratory performance improvements positively relate to the buyer’s financial performance, but these relationships are moderated by the buyer’s product innovation strategy. Exploratory performance is particularly important for firms pursuing a high innovation strategy to maximize financial performance.

The Most General Mental Act

Abstract: This chapter contributes to the ongoing debate over how to understand attention. It spells out and defends a novel account according to which attending is the most general type of mental act, that which one performs on some object if one performs any mental act on it at all. On this view, all mental acts are (to a first, rough approximation) species of attending. The view is novel in going against the grain of virtually all extant accounts, which work by identifying the purported unique functional role of attention. It is inspired by Timothy Williamson’s account of knowledge as the most general factive mental state. Beyond the Williamsonian thin explanation of knowledge, the account of attention as the most general mental act is animated by two striking pre-theoretical features of attention, dubbed ubiquity and heterogeneity. The hope of accommodating these twin features seems to drive at least two other extant accounts of attention, very different from the one proposed here, offered by Mole and Wu, respectively. However, as the chapter explains, both Mole’s and Wu’s accounts fall short, leaving room for the novel account defended here, which does adequately capture both features.

Contactless optical hygrometry in LACIS-T

Abstract: Abstract. The Fast Infrared Hygrometer (FIRH), employing open-path tunable diode laser absorption spectroscopy at the wavelengths near 1364.6896 nm line, was adapted to perform contactless humidity measurements at the Turbulent Leipzig Aerosol Cloud Interaction Simulator (LACIS-T), a unique turbulent moist-air wind tunnel. The configuration of the setup allows for scanning at various positions without the need for repeated optics adjustments. We identified three factors which significantly influence the measurement – self-broadening of the absorption line, interference in the glass windows and parasitic absorption in the ambient air outside the tunnel – and developed correction methods which satisfactorily account for these effects. The comparison between FIRH and a reference hygrometer (dew-point mirror MBW 973) indicated a good agreement within the expected errors across the wide range of water vapor concentration 1.0 . . . 6.1 cm−3 (equivalent to dew-point temperature of −5.4 . . . + 21 °C at the temperature of 23 °C). High temporal resolution (∼2 kHz) allowed for studying turbulent fluctuations in the course of intensive mixing of two air streams which had the same mean velocity but differed in temperature and humidity, including also the settings for which the mixture can be supersaturated. The obtained results complement the previous characterizations of turbulent velocity and temperature fields in LACIS-T. The variance of water vapor concentration exhibits a maximum in the center of the mixing zone which coincides with the steepest gradient.

Applications of Intersectionality Theory to Enhance Career Development Interventions in Response to COVID-19

Abstract: The school counseling profession has an ethical responsibility to provide and advocate for individual students' career planning and development, while expanding school counselors' own multicultural and social justice advocacy to become effective culturally competent professionals. Additional literature is needed to identify how school counselors can adapt their career counseling approaches to fit the unique challenges and barriers of historically marginalized students both during and after the global COVID-19 pandemic. We describe how school counselors can use intersectionality theory as a framework for career development with marginalized populations in response to COVID-19 and its impact on the economic decline.

Porous Ionic Liquid Derived Materials for CO 2 Emissions Mitigation

Abstract: The purpose of this chapter is to demonstrate alternative porous IL-grafted materials for CO2 capture and reuse. ILs are known for their affinity and selectivity towards CO2, however, their liquid nature restrains the scope of applications. The effort to gather IL features within porous materials has therefore widened their functionalities. Since the choice of support is essential to achieve the adequate porosity, the chapter is organized according to the nature of support, namely organic, inorganic and hybrid or crystalline frameworks materials. The discussion is mainly based on organic supports since the desired functionality with modulated properties can be introduced into the porous materials by using PIL-based materials. In addition, in all sections, the methodologies and support trends are highlighted to facilitate the development of future tailored materials.