Decreased Enhancer-Promoter Proximity Accompanying Enhancer Activation.

Enhancers can regulate the promoters of their target genes over very large genomic distances. It is widely assumed that mechanisms of enhancer action involve the reorganization of three-dimensional chromatin architecture, but this is poorly understood. The predominant model involves physical enhancer-promoter interaction by looping out the intervening chromatin. However, studying the enhancer-driven activation of the Sonic hedgehog gene (Shh), we have identified a change in chromosome conformation that is incompatible with this simple looping model. Using super-resolution 3D-FISH and chromosome conformation capture, we observe a decreased spatial proximity between Shh and its enhancers during the differentiation of embryonic stem cells to neural progenitors. We show that this can be recapitulated by synthetic enhancer activation, is impeded by chromatin-bound proteins located between the enhancer and the promoter, and appears to involve the catalytic activity of poly (ADP-ribose) polymerase. Our data suggest that models of enhancer-promoter communication need to encompass chromatin conformations other than looping.

Risk Factors for Major Pregnancy Complications in Female Cardiothoracic Surgeons.

OBJECTIVE: To describe the incidence of and risk factors for pregnancy complications in female cardiothoracic surgeons compared to women of similar sociodemographic profiles. SUMMARY BACKGROUND DATA: Female cardiothoracic surgeons often postpone childbearing, but little is known about their pregnancy outcomes. METHODS: A self-administered survey was distributed to US cardiothoracic surgeons/trainees in 2023. Surgeons with ≥1 live birth were queried on maternal work hours during pregnancy and major antenatal pregnancy complications. Male surgeons answered on behalf of non-surgeon childbearing partners (female non-surgeons). RESULTS: The study included 255 surgeons (63.53% male; 36.47% female). Compared to female surgeons, male surgeons more often had partners who were not employed outside the home (25.64% vs. 13.33%, P<0.001). Female surgeons were older than female non-surgeons at first live birth (34.494.41 vs. 31.454.16, P<0.001), more often worked >60 hours/week during pregnancy (70.33% vs. 14.08%, P<0.001), and more often had pregnancy complications (45.16% vs. 27.16%, P=0.003; OR 1.78, 95%CI:1.01-3.13). Among female surgeons, 18.28% reduced work hours during pregnancy. During their third trimester, 54.84% worked >6 overnight calls/month and 72.04% operated >12 hours/week. Age35yrs (OR 3.28, 95%CI 1.27-8.45) and operating >12 hours/week during the third trimester (OR 3.72, 95%CI 1.04-13.30) were associated with pregnancy complications. CONCLUSIONS: Female cardiothoracic surgeons are more likely to experience major pregnancy complications than non-surgeon partners of their male peers. Long operative hours during pregnancy and older maternal age are significant risk factors for pregnancy complications. To advance gender equity, policies to protect maternal-fetal health and facilitate childbearing during training and early career are needed.

Do vasoactive medications impact donor hearts clinical outcomes in pediatric heart transplantation?

OBJECTIVES: There is limited data examining donor vasopressor and/or inotrope medications (vasoactives) on pediatric orthotopic heart transplant (OHT) outcomes. We aim to evaluate the effects of vasoactives on pediatric OHT outcomes. METHODS: The United Network for Organ Sharing database was retrospectively reviewed from January 2000 to March 2018 for donor hearts. Exclusion criteria included multiorgan transplants and recipient age >18. Donors receiving vasoactives at the time of procurement were compared to donors not on vasoactives, including the number of vasoactives and the type. End-points of interest were survival at 30 days and 1 year as well as post-transplant rejection at 1 year. Logistic and Cox models were used to quantify survival end-points. RESULTS: Of 6462 donors, 3187 (49.3%) were receiving at least one vasoactive. Comparing any vasoactive medication versus none, there was no difference in 30-day survival (p = .27), 1 year survival (p = .89), overall survival (p = .68), or post-transplant rejection (p = .98). There was no difference in 30-day survival for donors receiving 2 or more vasoactive infusions (p = .89), 1 year survival (p = .53), overall survival (p = .75), or post-transplant rejection at 1 year (p = .87). Vasopressin was associated with decreased 30-day mortality (OR = 0.22; p = .028), dobutamine with decreased 1-year mortality (OR = 0.37; p = .036), overall survival (HR = 0.51; p = .003), and decreased post-transplant rejection (HR = 0.63; p = .012). CONCLUSIONS: There is no difference in pediatric OHT outcomes when the cardiac donor is treated with vasoactive infusions at procurement. Vasopressin and dobutamine were associated with improved outcomes. This information can be used to guide medical management and donor selection.

Developmentally regulated Shh expression is robust to TAD perturbations.

Topologically associating domains (TADs) have been proposed to both guide and constrain enhancer activity. Shh is located within a TAD known to contain all its enhancers. To investigate the importance of chromatin conformation and TAD integrity on developmental gene regulation, we have manipulated the Shh TAD - creating internal deletions, deleting CTCF sites, and deleting and inverting sequences at TAD boundaries. Chromosome conformation capture and fluorescence in situ hybridisation assays were used to investigate the changes in chromatin conformation that result from these manipulations. Our data suggest that these substantial alterations in TAD structure have no readily detectable effect on Shh expression patterns or levels of Shh expression during development - except where enhancers are deleted - and result in no detectable phenotypes. Only in the case of a larger deletion at one TAD boundary could ectopic influence of the Shh limb enhancer be detected on a gene (Mnx1) in the neighbouring TAD. Our data suggests that, contrary to expectations, the developmental regulation of Shh expression is remarkably robust to TAD perturbations.

PHARMACOKINETICS OF A SINGLE DOSE OF INTRAMUSCULAR AND ORAL MELOXICAM IN YELLOW STINGRAYS (UROBATIS JAMAICENSIS).

Elasmobranchs are popular display animals in public aquaria and zoos, but medical management gaps remain in the understanding of the pharmacokinetics of analgesics and pain management in these species. Meloxicam is a nonsteroidal anti-inflammatory drug that has been evaluated intravenously and intramuscularly in teleosts, but has yet to be studied in any elasmobranch species. The pharmacokinetics of meloxicam were determined in 17 yellow stingrays (Urobatis jamaicensis). All stingrays were determined to be healthy from complete physical examinations and baseline bloodwork performed prior to study inclusion. A single dose of 1 mg/kg meloxicam intramuscularly was administered to all rays, followed by a 2 mg/kg oral dose after an 8 wk washout period. Blood samples were collected from the mesopterygial vein at baseline and nine time points up to 96 h after administration of meloxicam. Plasma concentrations were determined using reversed-phase high-performance liquid chromatography. Pharmacokinetic analysis was performed using a noncompartmental technique. The mean peak plasma concentrations for intramuscular and oral meloxicam were 1.29 and 0.42 µg/ml, respectively. The mean terminal half-lives of meloxicam after intramuscular and oral administration were 5.75 and 15.46 h, respectively. Based on these findings, the recommended meloxicam dosage and frequency for yellow stingrays is 2 mg/kg orally once daily. Due to rapid elimination with the intramuscular administration, maintaining clinically relevant plasma concentrations may be difficult using this route. Further studies are needed to determine multidose pharmacokinetics of meloxicam in yellow stingrays, as well as single-dose and multidose pharmacokinetics in other elasmobranch species.

CLINICOPATHOLOGIC EVALUATION OF AN EX SITU POPULATION OF ADULT AFRICAN WHITE-BELLIED PANGOLIN (PHATAGINUS TRICUSPIS).

Death due to illegal trade and trafficking serves as the largest threat to pangolins in their geographic range countries. Appropriate veterinary care is essential to the welfare of sick or debilitated pangolins. Given the challenge of comprehensive physical examination of this species due to its unique anatomic features and poorly studied physiology, laboratory diagnostics can provide essential information to guide appropriate medical care. This retrospective study included previously analyzed blood and urine samples collected from adult (n = 17) African white-bellied pangolins (Phataginus tricuspis) under managed care that were sampled over a 4-yr period as part of routine veterinary examinations. Samples from clinically normal animals were used to summarize results for this species. Pangolins had a lymphocyte-predominant leukogram with a mean neutrophil to lymphocyte ratio of 0.83 (min-max: 0.13-4.81). Seasonal, sex, and age differences were present for several hematologic and serum biochemical analytes. Urine samples had a median urine specific gravity (USG) of 1.040 (min-max: 1.006-1.060), a neutral-to-basic urine pH (6.0-8.6), and contained mainly struvite crystals or infrequently calcium oxalate dihydrate crystals. Winter samples had higher USG than summer samples. The clinicopathologic data provided herein offers applicable information useful for the clinical management of pangolins.

SUCCESSFUL SURGICAL CORRECTION OF PHIMOSIS IN AMUR LEOPARDS (PANTHERA PARDUS ORIENTALIS) USING A CARBON DIOXIDE LASER: CASE SERIES.

Three juvenile (<1 yr of age), genetically related Amur leopards (Panthera pardus orientalis) were diagnosed with phimosis. In all cases, no clinical signs were identified, and phimosis was detected during routine examination. Surgical enlargement of the preputial orifice was performed successfully using carbon dioxide laser with a 0.25-mm tip and an 8-watt continuous wave setting. A linear incision on the ventral aspect of the preputial opening allowed for complete preputial extrusion followed by placement of simple-interrupted sutures on both sides of the incision. No postoperative complications were observed, and there was no evidence of phimosis recurrence at subsequent examinations. Preputioplasty with carbon dioxide laser was used to successfully manage Amur leopards with phimosis. Given relatedness of these cases, a genetic predisposition for phimosis development in Amur leopards must be considered.

REVIEW OF HISTOLOGIC LESIONS AND MORTALITY IN RIO CAUCA CAECILIANS (TYPHLONECTES NATANS) OVER A 22-YEAR PERIOD.

Rio Cauca caecilians (Typhlonectes natans) are a unique, fully aquatic species of amphibian from the order Gymnophiona. They are housed in several zoological institutions and aquaria with limited information available regarding health and disease. This retrospective study evaluates common pathologic findings and causes of mortality of Rio Cauca caecilians from three different institutions over a 22-y period. Comparisons to previous medical health surveys were conducted with evaluation according to age class and sex to determine whether the primary causes of mortality and common histologic findings have remained similar over time and between institutions. Between 1997 and 2019, the 62 mortalities included males (15/62; 24.2%), females (26/62; 41.9%), and undetermined sex (21/62; 33.9%). The majority of examined individuals were adult (38/62; 61.3%), followed by juveniles (13/62; 21.0%), neonates (9/62; 14.5%), and undetermined age class (2/62; 3.2%). Thirteen (21.0%) individuals were euthanatized. Adult females (16/62; 25.48%) represented the largest group. In adults, the most common lesion and contributor to death was renal disease (28/38; 73.7%) followed by skin disease (16/38; 42.1%), including oomycete dermatitis (8/38; 21.1%) from Saprolegnia sp. Other common findings included bacterial dermatitis, gastrointestinal nematodiasis, and adrenal hyperplasia. This retrospective study will provide a useful reference to help guide veterinary care, management decisions, and collection management planning for this caecilian species in managed care.

MEASUREMENT OF INTRAOCULAR PRESSURE USING REBOUND TONOMETRY IN ANESTHETIZED PERUVIAN FUR SEALS (ARCTOCEPHALUS AUSTRALIS) FROM PUNTA SAN JUAN, PERU.

Ocular disease in pinnipeds under human care is well described, and intraocular pressure (IOP) can be impacted by a variety of ophthalmic conditions. Species-specific reference parameters from clinically normal animals are instrumental for understanding how ophthalmic diseases may impact ocular pressures. IOP measurements were obtained using rebound tonometry from free-ranging Peruvian fur seals (Arctocephalus australis unnamed subspecies) at Punta San Juan, Peru, over a 6-yr period (2010-2016). Retrospective data obtained from 108 (81 adults and 27 neonates comprising 69 females and 39 males) anesthetized fur seals with normal anterior segment ophthalmic examinations was included in the analysis. Differences in IOP from each eye were compared to categorical variables (age, year, sex, restraint) using an independent-samples t test. All univariate results with a significance of P < 0.05 were included in multivariate analysis. Of the 13 general linear models evaluated, the top two for both the right and the left eye included age class when all variables were evaluated simultaneously. Neonates had significantly lower IOP values than adults in both the right eye (17.5 mm Hg; 95% confidence interval [CI]: 14.0-21.1 mm Hg compared to 33.5 mm Hg; 95% CI: 31.0-36.1 mm Hg, respectively) and the left eye (18.4 mm Hg; 95% CI: 14.4-22.5 mm Hg compared to 32.3 mm Hg; 95% CI: 29.3-35.3 mm Hg, respectively). Anesthesia method was not statistically significant (P > 0.05). This is the first report of normal IOP measurements for any fur seal species. Described data can be used to improve diagnosis and management of ocular alterations in pinnipeds.

BODY CONDITION OF EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA) EVALUATED BY COMPUTED TOMOGRAPHY.

Conservation efforts determining the health status of individuals can aid in assessing population health and sustainability. Body condition was determined in 65 free-ranging Eastern box turtles (Terrapene carolina carolina) from four locations in Vermilion County, Illinois, in the months of May, July, and September 2014, 2015, and 2016 using computed tomography (CT). Physical examinations were performed to determine morphometric measurements, and CT scans measured body fat. Twenty-three linear models were constructed to determine which morphometric measurements best correlated to fat content. The top two models of body fat included a relationship between mass and carapace width. Fat increases as both mass and carapace width increase. CT, while impractical for daily use, improved on previous methods of measuring body condition and created a calculation that can be applied broadly to Eastern box turtles. By understanding how measurements of mass and carapace width correlate to body condition, practitioners, researchers, and conservationists can evaluate chelonians with increased confidence in the accuracy of their assessment.

Successful, Full-Thickness Skin Graft in a Bald Eagle (Haliaeetus leucocephalus).

A subadult, male bald eagle (Haliaeetus leucocephalus) was evaluated after being found unable to fly, with large eschars on the dorsal head and right stifle. Because of the appearance and location, the lesions were believed to be caused by an electrical injury. Treatment included oral antibiotics, nonsteroidal anti-inflammatory drugs, pain medication, surgical debridement of the eschars, and trephining of the affected inner table of the cranium. A full-thickness skin graft was performed to expedite wound healing and minimize holding time. After 6 weeks, the bird had new feather growth on its dorsal head and was released. This is the first report, to our knowledge, of a nonmesh, full-thickness skin graft in an avian species. Full-thickness skin grafts should be considered as a surgical option in juvenile or adult avian patients with large dorsal head wounds.

Insidious Harm of Medication Diluents as a Contributor to Cumulative Volume and Hyperchloremia: A Prospective, Open-Label, Sequential Period Pilot Study.

OBJECTIVES: Although the potential dangers of hyperchloremia from resuscitation fluids continue to emerge, no study to date has considered the contribution of medication diluents to cumulative volume and hyperchloremia. This study compares saline versus dextrose 5% in water as the primary medication diluent and the occurrence of hyperchloremia in critically ill patients. DESIGN: Prospective, open-label, sequential period pilot study. SETTING: Medical ICU of a large academic medical center. PATIENTS: Adult patients admitted to the medical ICU were eligible for inclusion. Patients who were admitted for less than 48 hours, less than 18 years old, pregnant, incarcerated, or who had brain injury were excluded. INTERVENTIONS: Saline as the primary medication diluent for 2 months followed by dextrose 5% in water as the primary medication diluent for 2 months. MEASUREMENTS AND MAIN RESULTS: A total of 426 patients were included, 216 in the saline group and 210 in the dextrose 5% in water group. Medication diluents accounted for 63% of the total IV volume over the observation period. In the saline group, 17.9% developed hyperchloremia compared with 10.5% in the dextrose 5% in water group (p = 0.037), which was statistically significant in multivariable analysis (odds ratio, 0.50; 95% CI, 0.26-0.94; p = 0.031). In the saline group, 34.2% developed acute kidney injury versus 24.5% in the dextrose 5% in water group (p = 0.035); however, this was not statistically significant when adjusting for baseline covariates. No other significant differences in dysnatremias, insulin requirements, glucose control, ICU length of stay, or ICU mortality were observed. CONCLUSIONS: This study identified that medication diluents contribute substantially to the total IV volume received by critically ill patients. Saline as the primary medication diluent compared with dextrose 5% in water is associated with hyperchloremia, a possible risk factor for acute kidney injury.

Outcomes of an electronic social network intervention with neuro-oncology patient family caregivers.

INTRODUCTION: Informal family caregivers (FCG) are an integral and crucial human component in the cancer care continuum. However, research and interventions to help alleviate documented anxiety and burden on this group is lacking. To address the absence of effective interventions, we developed the electronic Support Network Assessment Program (eSNAP) which aims to automate the capture and visualization of social support, an important target for overall FCG support. This study seeks to describe the preliminary efficacy and outcomes of the eSNAP intervention. METHODS: Forty FCGs were enrolled into a longitudinal, two-group randomized design to compare the eSNAP intervention in caregivers of patients with primary brain tumors against controls who did not receive the intervention. Participants were followed for six weeks with questionnaires to assess demographics, caregiver burden, anxiety, depression, and social support. Questionnaires given at baseline (T1) and then 3-weeks (T2), and 6-weeks (T3) post baseline questionnaire. RESULTS: FCGs reported high caregiver burden and distress at baseline, with burden remaining stable over the course of the study. The intervention group was significantly less depressed, but anxiety remained stable across groups. CONCLUSIONS: With the lessons learned and feedback obtained from FCGs, this study is the first step to developing an effective social support intervention to support FCGs and healthcare providers in improving cancer care.

Feasibility of implementing an electronic social support and resource visualization tool for caregivers in a neuro-oncology clinic.

PURPOSE: The goals of this study were to assess the feasibility of a web-based application-electronic Social Network Assessment Program (eSNAP)-to automate the capture and visualization of family caregiver social network data of neuro-oncology patients. METHODS: Caregivers were recruited from a neuro-oncology clinic at an NCI-designated comprehensive cancer center. Participants completed baseline questionnaires on a laptop in clinic assessing demographic characteristics. After baseline, participants were randomly assigned to either create a social network visualization using eSNAP (intervention) or to usual care (control) condition. Those who used eSNAP provided likeability/usability data. All participants were asked to complete follow-up questionnaires at 3 and 6 weeks after baseline to determine feasibility of longitudinal study. RESULTS: We recruited 40 caregivers of patients with primary malignant brain tumor to participate in this study. Participants rated eSNAP usability and likeability highly, indicating that eSNAP would help them consider their available social support. At 3 weeks, 90% of participants completed questionnaires and 82.5% completed questionnaires at 6 weeks. CONCLUSIONS: There is a need to encourage family caregivers of patients with primary malignant brain tumor to engage their existing social network resources to help alleviate caregiver burden. Our findings suggest that our web-based application to address this issue is feasible to implement with high usability and likeability. This pilot study identified minor changes to the intervention to improve effectiveness and has implications for future research in this understudied population. TRIAL REGISTRATION: clinicaltrials.gov, protocol number NCT03026699.

The ACGME Fellowship in Congenital Cardiac Surgery: The Graduates' Perspective.

The creation of structured fellowship programs in congenital heart surgery (CHS) in the United States appears to have improved the training of congenital heart surgeons. However, the transition process between fellowship and clinical practice and the lack of senior mentorship continue to be major problems. We report the results of a survey of all graduates of accredited programs in CHS. A total of 35/51 (69%) graduates responded to the survey. Of 34 that are in practice, 31 (91%) did not feel ready to engage in solo CHS after completion of training. Even though 33 (97%) considered mentorship in the first few years of practice very important, almost 40% indicated inadequate mentorship. Several graduates continue to mainly assist and do not seem to be independent several years after graduating from their fellowship. On an open-ended question for additional comments, 15 respondents volunteered that a 1-year fellowship duration was not enough and seven stressed the importance of mentorship and the need for an adequate transition from fellowship to practice. Based on the results of the survey and our own experience, we propose the creation of a 1- or 2-year transitional junior faculty period to follow the 1-year formal training in CHS. We believe innovative approaches to improve the transition to clinical practice are required to maximize the likelihood of success among congenital heart surgery graduates.

PHARMACOKINETICS, EFFICACY, AND SAFETY OF VORICONAZOLE AND ITRACONAZOLE IN HEALTHY COTTONMOUTHS (AGKISTRODON PISCIVORUS) AND MASSASAUGA RATTLESNAKES (SISTRURUS CATENATUS) WITH SNAKE FUNGAL DISEASE.

Snake fungal disease (SFD; Ophidiomyces ophiodiicola) is posing a significant threat to several free-ranging populations of pitvipers. Triazole antifungals have been proposed for the treatment of mycoses in reptiles; however, data are lacking about their safety and efficacy in snakes with SFD. Study 1 investigated in vitro susceptibility, and identified that plasma concentrations >250 ng/ml (voriconazole) and >1,000 ng/ml (itraconazole) may be effective in vivo for SFD. In Study 2, the pharmacokinetics after a single subcutaneous voriconazole injection were assessed in apparently healthy free-ranging cottonmouths (Agkistrodon piscivorus). Based on pilot-study results, four snakes were administered a single injection of voriconazole (5 mg/kg). One pilot snake and three full-study snakes died within 12 hr of voriconazole administration. All surviving snakes maintained plasma concentrations >250 ng/ml for 12-24 hr. In Study 3, two Eastern massasaugas (Sistrurus catenatus) and a timber rattlesnake (Crotalus horridus horridus) diagnosed with SFD were treated with voriconazole delivered by subcutaneous osmotic pumps. The timber rattlesnake (12.1-17.5 mg/kg/hr) reached therapeutic concentrations, whereas the massasaugas (1.02-1.6 mg/kg/hr) did not. In Study 4, the pharmacokinetics of a single 10-mg/kg per-cloaca dose of itraconazole (Sporanox®) was evaluated in seven apparently healthy free-ranging cottonmouths. Similarly, the plasma and tissue concentrations did not meet therapeutic concentrations based on in vitro data. The data presented in this report serve as an initial step toward understanding the pharmacokinetics, efficacy, and safety of triazole antifungals in pitviper species with SFD. Further study is needed to determine the appropriate dose and route of administration of triazole antifungals in pitviper species.

The fornix provides multiple biomarkers to characterize circuit disruption in a mouse model of Alzheimer's disease.

Multivariate biomarkers are needed for detecting Alzheimer's disease (AD), understanding its etiology, and quantifying the effect of therapies. Mouse models provide opportunities to study characteristics of AD in well-controlled environments that can help facilitate development of early interventions. The CVN-AD mouse model replicates multiple AD hallmark pathologies, and we identified multivariate biomarkers characterizing a brain circuit disruption predictive of cognitive decline. In vivo and ex vivo magnetic resonance imaging (MRI) revealed that CVN-AD mice replicate the hippocampal atrophy (6%), characteristic of humans with AD, and also present changes in subcortical areas. The largest effect was in the fornix (23% smaller), which connects the septum, hippocampus, and hypothalamus. In characterizing the fornix with diffusion tensor imaging, fractional anisotropy was most sensitive (20% reduction), followed by radial (15%) and axial diffusivity (2%), in detecting pathological changes. These findings were strengthened by optical microscopy and ultrastructural analyses. Ultrastructual analysis provided estimates of axonal density, diameters, and myelination-through the g-ratio, defined as the ratio between the axonal diameter, and the diameter of the axon plus the myelin sheath. The fornix had reduced axonal density (47% fewer), axonal degeneration (13% larger axons), and abnormal myelination (1.5% smaller g-ratios). CD68 staining showed that white matter pathology could be secondary to neuronal degeneration, or due to direct microglial attack. In conclusion, these findings strengthen the hypothesis that the fornix plays a role in AD, and can be used as a disease biomarker and as a target for therapy.

Na+-K+-Cl- cotransporter (NKCC) maintains the chloride gradient to sustain pacemaker activity in interstitial cells of Cajal.

Interstitial cells of Cajal (ICC) generate electrical slow waves by coordinated openings of ANO1 channels, a Ca2+-activated Cl- (CaCC) conductance. Efflux of Cl- during slow waves must be significant, as there is high current density during slow-wave currents and slow waves are of sufficient magnitude to depolarize the syncytium of smooth muscle cells and PDGFRα+ cells to which they are electrically coupled. We investigated how the driving force for Cl- current is maintained in ICC. We found robust expression of Slc12a2 (which encodes an Na+-K+-Cl- cotransporter, NKCC1) and immunohistochemical confirmation that NKCC1 is expressed in ICC. With the use of the gramicidin permeabilized-patch technique, which is reported to not disturb [Cl-]i, the reversal potential for spontaneous transient inward currents (ESTICs) was -10.5 mV. This value corresponds to the peak of slow waves when they are recorded directly from ICC in situ. Inhibition of NKCC1 with bumetanide shifted ESTICs to more negative potentials within a few minutes and reduced pacemaker activity. Bumetanide had no direct effects on ANO1 or CaV3.2 channels expressed in HEK293 cells or L-type Ca2+ currents. Reducing extracellular Cl- to 10 mM shifted ESTICs to positive potentials as predicted by the Nernst equation. The relatively rapid shift in ESTICs when NKCC1 was blocked suggests that significant changes in the transmembrane Cl- gradient occur during the slow-wave cycle, possibly within microdomains formed between endoplasmic reticulum and the plasma membrane in ICC. Recovery of Cl- via NKCC1 might have additional consequences on shaping the waveforms of slow waves via Na+ entry into microdomains.

Thromboelastography--does it impact blood component transfusion in pediatric heart surgery?

BACKGROUND: The administration of blood products during pediatric cardiac surgery is common. We sought to determine if thromboelastography (TEG) is a cost-effective tool to reduce blood product transfusion in open pediatric cardiac surgery. MATERIALS AND METHODS: A retrospective case-control study was undertaken for 150 pediatric cardiac patients requiring cardiopulmonary bypass from January 2010-May 2012, in a University-affiliated pediatric hospital. Fifty sequential patients operated on when TEG was used were compared with 100 control patients before TEG availability. Groups were matched 2:1 for age and risk adjustment for congenital heart surgery score. Blood product utilization was compared between groups, as were outcomes metrics such as postoperative complications, length of stay, and hospital costs of transfusions. RESULTS: Demographic variables, risk adjustment for congenital heart surgery score classifications, and cardiopulmonary bypass times were similar between groups. Red cell and plasma transfusion were comparable between groups. TEG patients saw a substantial reduction in the administration of platelet (1 versus 2.2 U; P < 0.0001) and cryoprecipitate (0.7 versus 1.7 U; P < 0.0001) transfusions. A greater than 50% reductions in hospital costs of platelet ($595 versus $1309) and cryoprecipitate ($39 versus $94) transfusions were observed in the TEG group. Mortality, length of stay, ventilator requirements, postoperative bleeding, and thrombotic events were equivalent. CONCLUSIONS: Intraoperative TEG use reduced platelet and cryoprecipitate transfusions without an increase in postoperative complications. TEG is a cost-effective method to direct blood product replacement.