Biomechanical Analysis of Age-Dependent Changes in Fontan Power Loss.

The hemodynamics in Fontan patients with single ventricles rely on favorable flow and energetics, especially in the absence of a subpulmonary ventricle. Age-related changes in energetics for extracardiac and lateral tunnel Fontan procedures are not well understood. Vorticity (VOR) and viscous dissipation rate (VDR) are two descriptors that can provide insights into flow dynamics and dissipative areas in Fontan pathways, potentially contributing to power loss. This study examined power loss and its correlation with spatio-temporal flow descriptors (vorticity and VDR). Data from 414 Fontan patients were used to establish a relationship between the superior vena cava (SVC) to inferior vena cava (IVC) flow ratio and age. Computational flow modeling was conducted for both extracardiac conduits (ECC, n = 16) and lateral tunnels (LT, n = 25) at different caval inflow ratios of 2, 1, and 0.5 that corresponded with ages 3, 8, and 15+. In both cohorts, vorticity and VDR correlated well with PL, but ECC cohort exhibited a slightly stronger correlation for PL-VOR (>0.83) and PL-VDR (>0.89) than that for LT cohort (>0.76 and > 0.77, respectively) at all ages. Our data also suggested that absolute and indexed PL increase (p < 0.02) non-linearly as caval inflow changes with age and are highly patient-specific. Comparison of indexed power loss between our ECC and LT cohort showed that while ECC had a slightly higher median PL for all 3 caval inflow ratio examined (3.3, 8.3, 15.3) as opposed to (2.7, 7.6, 14.8), these differences were statistically non-significant. Lastly, there was a consistent rise in pressure gradient across the TCPC with age-related increase in IVC flows for both ECC and LT Fontan patient cohort. Our study provided hemodynamic insights into Fontan energetics and how they are impacted by age-dependent change in caval inflow. This workflow may help assess the long-term sustainability of the Fontan circulation and inform the design of more efficient Fontan conduits.

Impact of Age-related change in Caval Flow Ratio on Hepatic Flow Distribution in Fontan.

Background: The Fontan operation is a palliative technique for patients born with single ventricle heart disease. The superior vena cava (SVC), inferior vena cava (IVC), and hepatic veins are connected to the pulmonary arteries in a total cavopulmonary connection by an extracardiac (EC) conduit or a lateral tunnel (LT) connection. A balanced hepatic flow distribution (HFD) to both lungs is essential to prevent pulmonary arteriovenous malformations and cyanosis. HFD is highly dependent on the local hemodynamics. Objective: The effect of age-related changes in caval inflows on HFD was evaluated using cardiac MRI (CMR) data and patient-specific computational fluid dynamics (CFD) modeling. Methods: SVC and IVC flow from 414 Fontan patients were collected to establish a relationship between SVC:IVC flow ratio and age. CFD modeling was performed in 60 (30 EC and 30 LT) patient models to quantify the HFD that corresponded to patient ages of 3, 8, and 15 years, respectively. Results: SVC:IVC flow ratio inverted at ∼8 years of age, indicating a clear shift to lower body flow predominance. Our data showed that variation of HFD in response to age-related changes in caval inflows (SVC:IVC = 2,1, and 0.5 corresponded to ages 3, 8, and 15+ respectively) was not significant for EC but statistically significant for LT cohorts. For all three caval inflow ratios, a positive correlation existed between the IVC flow distribution to both the lungs and the HFD. However, as the SVC:IVC ratio changed from 2→0.5 (age 3→15+), the correlation's strength decreased from 0.87→0.64, due to potential flow perturbation as IVC flow momentum increased. Conclusion: Our analysis provided quantitative insights into the impact of the changing caval inflows on Fontan's long-term HFD, highlighting the importance of including SVC:IVC variations over time to understand Fontan's long-term hemodynamics. These findings broaden our understanding of Fontan hemodynamics and patient outcomes. Clinical Perspective: With improvement in standard of care and management of single ventricle patients with Fontan physiology, the population of adults with Fontan circulation is increasing. Consequently, there is a clinical need to comprehend the impact of patient growth on Fontan hemodynamics. Using CMR data, we were able to quantify the relationship between changing caval inflows and somatic growth. We then used patient-specific computational flow modeling to quantify how this relationship affected the distribution of long-term hepatic flow in extracardiac and lateral tunnel Fontan types. Our findings demonstrated the significance of including SVC:IVC changes over time in CFD modeling to learn more about the long-term hemodynamics of Fontan. Fontan surgical approaches are increasingly planned and optimized using computational flow modeling. For a patient undergoing a Fontan procedure, the workflow presented in this study that takes into account the variations in Caval inflows over time can aid in predicting the long-term hemodynamics in a planned Fontan pathway.

Bridging the gap between conventional and alternative medicine.

BACKGROUND: The use of various forms of complementary and alternative medicine (CAM) has become widespread. We investigated this use in Madison, Wisconsin. METHODS: We conducted semistructured indepth interviews focused on the knowledge, attitudes, and behaviors of a random sample of 17 patients who had used both CAM and conventional therapies during the past year. Participants were recruited using telephone listings. Twenty alternative practitioners were selected to represent the major modalities. The topics discussed included healing philosophy, choices of therapeutic methods, and ideas concerning concurrent use of differing therapeutic modalities. An 8-member multidisciplinary team analyzed the transcripts individually and in group meetings. RESULTS: Four major themes emerged from the interview data: (1) holism, (2) empowerment, (3) access, and (4) legitimization. Both patients and providers distinguished between the socially legitimized and widely accessible but disempowering and mechanistic attributes of conventional medicine and the holistic and empowering but relatively less accessible and less legitimate nature of alternative healing. There was a strong call for integrating the best aspects of both. CONCLUSIONS: Practitioners and users of alternative therapies in the Madison area confirmed both the alternative and complementary natures of unconventional health care, called for more integrated and accessible health care, and provided insights that could be useful in bridging the gap between conventional and alternative medicine.

Cofactor-Bound Cross-Linked Enzyme Crystals (CLEC) of Alcohol Dehydrogenase.

Horse liver alcohol dehydrogenase was crystallized in the presence of its cofactor. The cross-linked enzyme crystals (CLECs) produced showed good catalytic activity without the addition of extra cofactor (see scheme). The enantioselectivity and stereochemical preference of the CLEC were the same as with the soluble enzyme, and both cofactor and enzyme were considerably more stable in CLEC form. Cofactor regeneration studies on the reduction of cinnemaldehyde indicate the potential for a high level of catalyst productivity.

Free-solution isoelectric focusing for the purification of Staphylococcus aureus enterotoxin C1.

A free-solution isoelectric focusing protocol was developed for the preparative purification of Staphylococcus aureus enterotoxin C1 (SEC1). A toxin consisting of a single isoelectric species, pI 8.8, was purified. Thirty-nine milligrams of SEC1 was recovered from 3 liters of culture supernatant. This significantly improved purification scheme utilized ammonium sulfate precipitation and the Bio-Rad Rotofor isoelectric cell to complete isolation in 2 days, thereby avoiding the protein degradation prevalent when published procedures are used. The purification protocol developed here for SEC1 is used to illustrate the utility of Rotofor fractionation in the general purification of bacterial exotoxins.

Supplemental oxygen delivery to the nonventilated neonate.

Oxygen is one of the most commonly administered drugs in the neonatal intensive care unit. A variety of techniques exists to deliver oxygen to infants who are not on a ventilator or who are not receiving positive pressure. These techniques include oxygen hood, nasal cannula, face mask delivery or "free flow," and "flooding" the incubator with oxygen. Because each technique has unique advantages and disadvantages, the choice is frequently dependent on style. Recent advances in incubator technology have improved the delivery of supplcmental oxygen by incubator flooding. This technique is generally underutilized, but it has some advantages over thc other modalities in certain clinical scenarios. The neonatal nurse needs to be aware of the characteristics of the various oxygen delivery technologies and the tools needed to optimally care for infants who are dependent on supplemental oxygen.

Cross-linked protein crystals for vaccine delivery.

The progress toward subunit vaccines has been limited by their poor immunogenicity and limited stability. To enhance the immune response, subunit vaccines universally require improved adjuvants and delivery vehicles. In the present paper, we propose the use of cross-linked protein crystals (CLPCs) as antigens. We compare the immunogenicity of CLPCs of human serum albumin with that of soluble protein and conclude that there are marked differences in the immune response to the different forms of human serum albumin. Relative to the soluble protein, crystalline forms induce and sustain over almost a 6-month study a 6- to 10-fold increase in antibody titer for highly cross-linked crystals and an approximately 30-fold increase for lightly cross-linked crystals. We hypothesize that the depot effect, the particulate structure of CLPCs, and highly repetitive nature of protein crystals may play roles in the enhanced production of circulating antibodies. Several features of CLPCs, such as their remarkable stability, purity, biodegradability, and ease of manufacturing, make them highly attractive for vaccine formulations. This work paves the way for a systematic study of protein crystallinity and cross-linking on enhancement of humoral and T cell responses.

Computer provides definite linen distribution and control mechanism.

For the past 10 years or so, large laundries have been concerned with productivity. While productivity has increased 10 to 20 percent, the linen replacement cost in these same laundries has more than doubled. It will not suffice for these laundries to point toward the hospitals they serve and imply that linen service and control is solely a hospital management problem. As long as proven technology is available, these laundries have an inherent responsibility to provide hospital management with the data necessary to pinpoint and correct linen consumption and replacement problems.