Hematological Disorders and Pulmonary Hypertension

Pulmonary hypertension (PH), a serious disorder with a high morbidity and mortality rate, is known to occur in a number of unrelated systemic diseases. Several hematological disorders such as sickle cell disease, thalassemia and myeloproliferative diseases develop PH which worsens the prognosis. Associated oxidant injury and vascular inflammation cause endothelial damage and dysfunction. Pulmonary vascular endothelial damage/dysfunction is an early event in PH resulting in the loss of vascular reactivity, activation of proliferative and antiapoptotic pathways leading to vascular remodeling, elevated pulmonary artery pressure, right ventricular hypertrophy and premature death. Hemolysis observed in hematological disorders leads to free hemoglobin which rapidly scavenges nitric oxide (NO), limiting its bioavailability, and leading to endothelial dysfunction. In addition, hemolysis releases arginase into the circulation which converts L-arginine to ornithine, thus bypassing NO production. Furthermore, treatments for hematological disorders such as immunosuppressive therapy, splenectomy, bone marrow transplantation, and radiation have been shown to contribute to the development of PH. Recent studies have shown deregulated iron homeostasis in patients with cardiopulmonary diseases including pulmonary arterial hypertension (PAH). Several studies have reported low iron levels in patients with idiopathic PAH, and iron deficiency is an important risk factor. This article reviews PH associated with hematological disorders and its mechanism; and iron homeostasis and its relevance to PH

Congenital heart disease in the newborn requiring early intervention

Although antenatal diagnostic technique has considerably improved, precise detection and proper management of the neonate with congenital heart disease (CHD) is always a great concern to pediatricians. Congenital cardiac malformations vary from benign to serious conditions such as complete transposition of the great arteries (TGA), critical pulmonary and aortic valvular stenosis/atresia, hypoplastic left heart syndrome (HLHS), obstructed total anomalous pulmonary venous return (TAPVR), which the baby needs immediate diagnosis and management for survival. Unfortunately, these life threatening heart diseases may not have obvious evidence early after birth, most of the clinical and physical findings are nonspecific and vague, which makes the diagnosis difficult. High index of suspicion and astute acumen are essential to decision making. When patent ductus arteriosus (PDA) is opened widely, many serious malformations may not be noticed easily in the early life, but would progress as severe acidosis/shock/cyanosis or even death as PDA constricts after few hours to days. Ductus dependent congenital cardiac lesions can be divided into the ductus dependent systemic or pulmonary disease, but physiologically quite different from each other and treatment strategy has to be tailored to the clinical status and cardiac malformations. Inevitably early presentation is often regarded as a medical emergency. Differential diagnosis with inborn error metabolic disorders, neonatal sepsis, persistent pulmonary hypertension of the newborn (PPHN) and other pulmonary conditions are necessary. Urgent identification of the newborn at such high risk requires timely referral to a pediatric cardiologist, and timely intervention is the key in reducing mortality and morbidity. This following review deals with the clinical presentations, investigative modalities and approach to management of congenital cardiac malformations presenting in the early life

A Novel Adaptation of a Parent-Child Observational Assessment Tool for Appraisals and Coping in Children Exposed to Acute Trauma

Background: Millions of children worldwide are exposed to acute potentially traumatic events (PTEs) annually. Many children and their families experience significant emotional distress and/or functional impairment following PTEs. While current research has begun to highlight a role for early appraisals and coping in promoting or preventing full recovery from PTEs, the exact nature of the relationships among appraisals, coping, and traumatic stress reactions as well as how appraisals and coping behaviors are influenced by the child\u27s environment (e.g., parents) remains unclear; assessment tools that reach beyond self-report are needed to improve this understanding. Objective: The objective of the current study is to describe the newly created Trauma Ambiguous Situations Tool (TAST; i.e., an observational child–parent interview and discussion task that allows assessment of appraisals, coping, and parent–child processes) and to report on initial feasibility and validation of TAST implemented with child–parent dyads in which children were exposed to a PTE. Method: As part of a larger study on the role of biopsychosocial factors in posttraumatic stress reactions, children (aged 8–13) and parents (n=25 child–parent dyads) completed the TAST during the child\u27s hospitalization for injury. Results: Children and parents engaged well with the TAST. The time to administer the TAST was feasible, even in a peri-trauma context. The TAST solicited a wide array of appraisals (threat and neutral) and coping solutions (proactive and avoidant). Forced-choice and open-ended appraisal assessments provided unique information. The parent–child discussion portion of the TAST allowed for direct observation of parent–child processes and demonstrated parental influence on children\u27s appraisals and coping solutions. Conclusions: The TAST is a promising new research tool, which may help to explicate how parents influence their child\u27s developing appraisals and coping solutions following a PTE. More research should examine the relationships of appraisals, coping, and parent–child processes assessed by the TAST with traumatic stress outcomes

Relational grounding facilitates development of scientifically useful multiscale models

We review grounding issues that influence the scientific usefulness of any biomedical multiscale model (MSM). Groundings are the collection of units, dimensions, and/or objects to which a variable or model constituent refers. To date, models that primarily use continuous mathematics rely heavily on absolute grounding, whereas those that primarily use discrete software paradigms (e.g., object-oriented, agent-based, actor) typically employ relational grounding. We review grounding issues and identify strategies to address them. We maintain that grounding issues should be addressed at the start of any MSM project and should be reevaluated throughout the model development process. We make the following points. Grounding decisions influence model flexibility, adaptability, and thus reusability. Grounding choices should be influenced by measures, uncertainty, system information, and the nature of available validation data. Absolute grounding complicates the process of combining models to form larger models unless all are grounded absolutely. Relational grounding facilitates referent knowledge embodiment within computational mechanisms but requires separate model-to-referent mappings. Absolute grounding can simplify integration by forcing common units and, hence, a common integration target, but context change may require model reengineering. Relational grounding enables synthesis of large, composite (multi-module) models that can be robust to context changes. Because biological components have varying degrees of autonomy, corresponding components in MSMs need to do the same. Relational grounding facilitates achieving such autonomy. Biomimetic analogues designed to facilitate translational research and development must have long lifecycles. Exploring mechanisms of normal-to-disease transition requires model components that are grounded relationally. Multi-paradigm modeling requires both hyperspatial and relational grounding

Periodontal disease and atherosclerotic vascular disease: Does the evidence support an independent association?: A scientific statement from the American heart association

A link between oral health and cardiovascular disease has been proposed for more than a century. Recently, concern about possible links between periodontal disease (PD) and atherosclerotic vascular disease (ASVD) has intensified and is driving an active field of investigation into possible association and causality. The 2 disorders share several common risk factors, including cigarette smoking, age, and diabetes mellitus. Patients and providers are increasingly presented with claims that PD treatment strategies offer ASVD protection; these claims are often endorsed by professional and industrial stakeholders. The focus of this review is to assess whether available data support an independent association between ASVD and PD and whether PD treatment might modify ASVD risks or outcomes. It also presents mechanistic details of both PD and ASVD relevant to this topic. The correlation of PD with ASVD outcomes and surrogate markers is discussed, as well as the correlation of response to PD therapy with ASVD event rates. Methodological issues that complicate studies of this association are outlined, with an emphasis on the terms and metrics that would be applicable in future studies. Observational studies to date support an association between PD and ASVD independent of known confounders. They do not, however, support a causative relationship. Although periodontal interventions result in a reduction in systemic inflammation and endothelial dysfunction in short-term studies, there is no evidence that they prevent ASVD or modify its outcomes