The Role of Clinic Preparedness to Support Patients and Strengthen the Medical System During and After a Pandemic.

Pediatric clinic preparedness is essential to improve the care and health outcomes for children during a pandemic and to decrease the burden on hospital systems. Clinic preparedness is a process that involves a well thought out plan that includes coordination with staff, open communication between the clinic and patient families, and collaboration with community partners. Planning for disasters can decrease some of the risks for our most vulnerable patients, including children and youth with special health care needs. There are plans, coalitions, and community partners that can help clinics in their preparedness journey.

Effects of environmental levels of cadmium, lead and mercury on human renal function evaluated by structural equation modeling.

A relationship between exposure to heavy metals, including lead and cadmium, and renal dysfunction has long been suggested. However, modeling of the potential additive, or synergistic, impact of metals on renal dysfunction has proven to be challenging. In these studies, we used structural equation modeling (SEM), to investigate the relationship between heavy metal burden (serum and urine levels of lead, cadmium and mercury) and renal function using data from the NHANES database. We were able to generate a model with goodness of fit indices consistent with a well-fitting model. This model demonstrated that lead and cadmium had a negative relationship with renal function, while mercury did not contribute to renal dysfunction. Interestingly, a linear relationship between lead and loss of renal function was observed, while the maximal impact of cadmium occurred at or above serum cadmium levels of 0.8 µg/L. The interaction of lead and cadmium in loss of renal function was also observed in the model. These data highlight the use of SEM to model interaction between environmental contaminants and pathophysiology, which has important implications in mechanistic and regulatory toxicology.

Structural equation modeling highlights the potential of Kim-1 as a biomarker for chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a major public health problem, and despite continued research in the field, there is still a need to identify both biomarkers of risk and progression, as well as potential therapeutic targets. Structural equation modeling (SEM) is a family of statistical techniques that has been utilized in the fields of sociology and psychology for many years; however, its utilization in the biological sciences is relatively novel. SEM's ability to investigate complex relationships in an efficient, single model could be utilized to understand the progression of CKD, as well as to develop a predictive model to assess kidney status in the patient. METHODS: Fischer 344 rats were fed either an ad libitum diet or a calorically restricted diet, and a time-course study of kidney structure and function was performed. EQS, a SEM software package, was utilized to generate five CKD models of the Fisher 344 rat and identify relationships between measured variables and estimates of kidney damage and kidney function. RESULTS: All models identified strong relationships between a biomarker for CKD, kidney injury molecule-1 (Kim-1) and kidney damage, in the Fischer 344 rat CKD model. Models also indicate a strong relationship between age and renal damage and dysfunction. CONCLUSION: SEM can be used to model CKD and could be useful to examine biomarkers in CKD patients.

Histamine effects on endothelial cell fibronectin interaction studied by atomic force microscopy.

Atomic force microscopy was used to investigate the cellular response to histamine, one of the major inflammatory mediators that cause endothelial hyperpermeability and vascular leakage. AFM probes were labeled with fibronectin and used to measure binding strength between alpha5beta1 integrin and fibronectin by quantifying the force required to break single fibronectin-integrin bonds. The cytoskeletal changes, binding probability, and adhesion force before and after histamine treatment on endothelial cells were monitored. Cell topography measurements indicated that histamine induces cell shrinkage. Local cell stiffness and binding probability increased twofold after histamine treatment. The force necessary to rupture single alpha5beta1-fibronectin bond increased from 34.0 +/- 0.5 pN in control cells to 39 +/- 1 pN after histamine treatment. Experiments were also conducted to confirm the specificity of the alpha5beta1-fibronectin interaction. In the presence of soluble GRGDdSP the probability of adhesion events decreased >50% whereas the adhesion force between alpha5beta1 and fibronectin remained unchanged. These data indicate that extracellular matrix-integrin interactions play an important role in the endothelial cell response to changes of external chemical mediators. These changes can be recorded as direct measurements on live endothelial cells by using atomic force microscopy.