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Biomedical subjects

R L Horst

Publications and source records attributed to R L Horst.

At least 55 records · Page 3Linked to original sources
PubMed1999

Ca2+-ATPases and their expression in the mammary gland of pregnant and lactating rats.

The transcellular Ca2+ fluxes required for milk production must be rigorously regulated to maintain the low cytosolic Ca2+ concentrations critical to cell function. Ca2+-ATPases play a critical role in the maintenance of this cellular Ca2+ homeostasis. Using RT-PCR and sequencing, we identified six Ca2+ pumps in lactating mammary tissue. Three plasma membrane Ca2+-ATPases (PMCAs) were found (PMCA1b, PMCA2b, and PMCA4b). Two sarco (endo)plasmic reticulum Ca2+-ATPases (SERCAs) were identified (SERCA2 and SERCA3), and the rat homologue to the yeast Golgi Ca2+-ATPase RS-10 was also found. The pattern of mRNA expression of each of these pumps was examined in rat mammary tissue from the 7th day of pregnancy to the 21st day of lactation. Northern blots revealed increased mRNA expression for all Ca2+ pumps by the 14th day of lactation, and transcripts continued to increase through the 18th day of lactation. PMCA1b, PMCA4b, SERCA2, and SERCA3 showed the lowest levels of expression. RS-10 transcripts were more abundant than SERCA2, SERCA3, PMCA1b, and PMCA4b. RS-10 was the only pump to increase in expression before parturition. PMCA2b was the most abundant transcript found in lactating mammary tissue. At peak lactation, expression of PMCA2b approached that of actin. The high expression, high affinity for Ca2+, and high activity at low calmodulin concentrations exhibited by PMCA2b suggest that it is uniquely suited for maintenance of Ca2+ homeostasis in the lactating mammary gland. The pattern of expression and abundance of RS-10 suggest that it is a candidate for the Golgi Ca2+-ATPase shown to be important in maintaining the Golgi Ca2+ concentration required for casein synthesis and micelle formation.

Animals↗
PubMed1999

Differential effects of 20-epi vitamin D analogs on the vitamin D receptor homodimer.

Vitamin D analogs have received increased attention because of their possible therapeutic benefits in treating osteoporosis and various proliferative disorders. Several analogs were examined for their effects on DNA binding of the vitamin D receptor (VDR) homodimer complex with the murine osteopontin vitamin D response element. All of the tested analogs increased complex binding by recombinant human VDR in the electrophoretic mobility shift assay and notable differences in mobility of these complexes were observed. A panel of C-terminal anti-VDR antisera were screened for their ability to interact with analog-bound VDR homodimer complexes or as a heterodimer complex with recombinant human retinoid X receptor alpha (rhRXR alpha). Like calcitriol, analog-bound heterodimer complexes were largely resistant to interaction with these antisera; however, striking differences were observed with the various antisera in an analogous homodimer binding experiment. KH1060 and CB1093, analogs with 20-epi conformations, produced homodimer complexes that were 3- to 6-fold more resistant to supershifting with Ab180 compared with the hormone or EB1089. Chymotrypsin digestion in combination with Western blotting using a C-terminal anti-VDR antiserum revealed similar digestion patterns for all ligands. However, KH1060- and CB1093-bound VDR complexes were more resistant to digestion than either calcitriol or EB1089. Finally, the ability of these compounds to yield stable homodimer complexes was assessed by challenging preformed homodimer with the exogenous addition of rhRXR alpha extracts. Although new heterodimer complexes appeared in a time-dependent fashion, the preformed homodimer complexes exhibited stable binding throughout the time course of the experiment. The results indicate that VDR homodimers are targets of vitamin D analogs with differential effects on C-terminal protein conformation that may partially explain the varied biological responses of these compounds.

Amino Acid Sequence↗
PubMed1999

Modulation of fat-soluble vitamin concentrations and blood mononuclear leukocyte populations in milk replacer-fed calves by dietary vitamin A and beta-carotene.

Dairy calves (n = 18), separated from dams at birth, were fed 1 L of pooled-colostrum. For the remaining 7 wk of the study, they were fed one of three diets consisting of either a custom-formulated milk replacer without vitamin A (controls), or supplemented with retinyl palmitate (equivalent to 32,000 IU of vitamin A/d) or with beta-carotene (equivalent to 20,000 IU of vitamin A/d). Plasma retinol, beta-carotene, and RRR-alpha-tocopherol concentrations were lowest at birth, and increased substantially from birth to 1 wk postpartum in all groups, a probable consequence of ingestion of colostrum. From 1 to 7 wk of age, retinol concentrations were greatest in retinyl palmitate-supplemented calves, intermediate in beta-carotene-supplemented calves and lowest in control calves. At 2, 3, 5, 6, and 7 wk, RRR-alpha-tocopherol concentrations were lower in retinyl palmitate-supplemented calves than in control calves. A negative correlation between plasma retinol and vitamin E concentrations existed from wk 2 to 7, suggesting vitamin A influences the absorption and distribution of RRR-alpha-tocopherol. Supplemental retinyl palmitate, but not beta-carotene, was associated with a reduction in the percentage of blood mononuclear leukocytes expressing CD2, CD4, and CD8-T cell antigens and interleukin-2 receptors. By wk 7, leukocyte populations from retinyl palmitate-supplemented calves were more similar to those from adult cattle than those from control calves, suggesting that supplemental vitamin A, as retinyl palmitate, affects the maturation of the neonatal immune system. Differences in the composition of blood mononuclear leukocyte populations may represent changes in immune competency.

Animals↗
PubMed1998

Selectivity of a C-terminal peptide antiserum for different DNA-binding states of the vitamin D receptor.

Antisera against peptides from the extreme N- and C-terminal regions of the VDR were evaluated. The N-terminal antiserum Ab192 functioned as a general-purpose antibody, being able to supershift the rhVDR in heterodimeric or homodimeric binding complexes in the EMSA, and detect both recombinant and native forms of the receptor on Western blots. The C-terminal antiserum, Ab195, also identified the receptor on Western blots, but in contrast, it displayed differential sensitivity to the conditions employed in the EMSA. In the presence of 1,25(OH)2D3, rhVDR, rhRXR alpha, and nonspecific DNA, Ab195 produced a weak supershift of the heterodimer complex in the EMSA. Significantly, omission of hormone from the binding buffer resulted in a complete shift of the bound complex with the antiserum. A complete supershift was also observed if only the nonspecific DNA was removed. Together these results indicate antiserum sensitivity to the ligand status in the rhVDR C-terminus as part of a DNA-bound heterodimer complex. Inclusion of 9-cis RA resulted in a modest increase in the amount of shifted product relative to 1,25(OH)2D3 alone. Finally, Ab195 completely supershifted the rhVDR homodimer binding complex under all tested conditions, including those analogous to where it was largely ineffective in shifting the heterodimer. Thus, Ab195 is sensitive to the ligand binding status of the VDR, discriminates heterodimer and homodimer binding interactions, and should provide an additional tool for exploring conformational changes induced in the receptor.

Amino Acid Sequence↗
PubMed1998

Pregnancy and lactation increase vitamin D-dependent intestinal membrane calcium adenosine triphosphatase and calcium binding protein messenger ribonucleic acid expression.

The calcium demands of pregnancy and lactation are known to up-regulate intestinal calcium absorption. Intestinal epithelial cells contain calcium ATPases and calcium binding proteins, which are believed to play important roles in intestinal calcium transport. However, the possible role of these two proteins in the up-regulation of intestinal calcium absorption observed in pregnancy and lactation is unknown. In this study, intestinal calcium ATPase (PMCA1), calcium binding protein (9K) (CaBP-9K), and vitamin D receptor (VDR) messenger RNA (mRNA) levels were determined by Northern analysis at different stages of pregnancy and early lactation in rats. Intestinal calcium ATPase and calcium binding protein mRNA levels did not differ significantly among nonpregnant rats and rats pregnant for 7 or 14 days. However, at 21 days gestation both calcium ATPase and calcium binding protein mRNA levels increased 2- to 3-fold. Calcium ATPase and calcium binding protein mRNA remained elevated at 7 days of lactation. Plasma 1,25-dihydroxyvitamin D3 (1,25-D3) concentration exhibited a similar pattern, rising markedly at 21 days gestation and remaining elevated in lactation. VDR mRNA levels did not change during the entire experiment. However, intestinal VDR content increased 2-fold in late pregnancy and lactation. These data suggest that transcription of calcium absorption factors is increased in late gestation and early lactation, perhaps mediated by increased plasma 1,25-dihydroxyvitamin D3 concentrations, and that the effects of gestation and lactation on VDR concentrations are probably posttranscriptional.

Animals↗
PubMed1998

Use of hydrochloric acid as a source of anions for prevention of milk fever.

Diets that contain high amounts of K induce milk fever by alkalinizing the blood of the cow, reducing the ability of homeostatic mechanisms to maintain normal blood concentrations of Ca. The addition of anions to the diet induces metabolic acidosis, which counteracts the alkalinizing effect of the high cation diets commonly fed to cows. Currently, anions are usually added as anionic salts, such as CaCl2 or MgSO4, and the pH of urine is often monitored to assess the degree of metabolic acidification resulting from the addition of anions to the diet. An alternative source of anions is HCl. In Experiment 1, the addition of HCl to the diet of cows that were not pregnant and not lactating significantly reduced the pH of urine and blood within 24 h. After HCl was removed from the diet, the pH of urine returned to baseline levels within 48 h. In Experiment 2, the inclusion of HCl into the prepartum ration of Jersey cows entering the third or greater lactation significantly reduced the incidence of milk fever from 63% of control cows to 11% of the treated cows and also reduced the degree of hypocalcemia that was experienced by the cows during the periparturient period. Plasma Ca concentrations at 0.5 d after calving were 5.33 +/- 0.52 and 6.69 +/- 0.51 mg/dl in the control and the HCl-treated cows, respectively. In Experiment 2, the prepartum consumption of the ration with HCl was greater than the consumption of the control ration. In liquid form, HCl remains dangerous to handle and corrosive to machinery. Commercial preparations of HCl mixed into common feed ingredients as a premix could offer an inexpensive and palatable alternative to anionic salts as a means of controlling the incidence of milk fever in dairy cows.

Acid-Base Equilibrium↗
PubMed1998

Effect of vitamins A and E on nitric oxide production by blood mononuclear leukocytes from neonatal calves fed milk replacer.

This study evaluated the effects of dietary vitamin A and E on the in vitro capacity of blood mononuclear leukocytes from calves to produce nitric oxide. Calves fed milk replacer received 100 IU/d of vitamin E as RRR-alpha-tocopherol or RRR-alpha-tocopheryl acetate and 0, 1700, 34,000, or 68,000 IU of vitamin A as retinyl acetate. Leukocytes from calves produced greater amounts of nitric oxide relative to leukocytes from adult cattle. The greater production of nitric oxide by calf leukocytes may be typical of the immature neonatal immune system. Nitric oxide production by calves fed RRR-alpha-tocopherol and either 1700 or 34,000 IU of vitamin A was less than that of calves in other groups and was more typical of production by leukocytes from cows. Our data suggest that optimal amounts of dietary vitamins A and E prompt the maturation of this response toward one that is more typical of adult cattle. Leukocytes from 1-wk-old calves produced less nitric oxide and were less responsive to stimuli than were leukocytes from older calves, a possible consequence of suppressive factors that were present in the ingested colostrum or in the circulation at birth.

Aging↗
PubMed1997

Calcium and vitamin D metabolism during lactation.

Calcium transfer to the fetus in late pregnancy and the subsequent transfer of calcium to milk represent the greatest challenges to calcium homeostasis in adult animals. The adaptation of the maternal calcium homeostatic mechanisms is the result of a complex interplay between calciotropic hormones and the tissues, intestine, bone, and kidney, responsible for providing the large amounts of calcium needed to support fetal skeletal growth and lactation. In this review, we will discuss general calcium homeostasis followed by a review of the specific adaptations required by the human, rat, and cow to meet fetal and lactational demands for calcium. Finally, we will review what is known about the regulation of calcium transfer from the plasma to the milk.

Animals↗
PubMed1997

Effects of the addition of potassium or sodium, but not calcium, to prepartum ratios on milk fever in dairy cows.

The effects of prepartum dietary concentrations of K, Na, and Ca on the incidence of periparturient hypocalcemia or milk fever was determined for older (> or = 4th lactation) Jersey cows. Cows were fed one of six diets differing in K and Ca contents. In addition, the effect of dietary Na (tested only at the high concentration of dietary Ca, and low concentration of dietary K) was examined. Treatments were arranged in an incomplete 2 x 4 factorial design; dietary Ca (0.5 or 1.5%) and dietary strong cations (1.1, 2.1, and 3.1% K or 1.3% Na) were the main effects. Dietary Ca did not significantly affect the incidence of milk fever of the degree of hypocalcemia experienced by the cows. Milk fever occurred in 2 of 20 cows that were fed the prepartum diet containing 1.1% K and 0.12% Na. Increasing dietary K to 2.1 or 3.1% increased the incidence of milk fever to 10 of 20 cows and 11 of 23 cows, respectively. Increasing dietary Na to 1.3% in the diet containing 1.5% Ca induced milk fever in 5 of 8 cows. Addition of strong cations to the prepartum diet increased blood and urine pH and reduced plasma hydroxyproline concentrations, suggesting that bone resorption of Ca is inhibited in cows fed high K or high Na diets as a result of metabolic alkalosis. These data demonstrated that dietary Ca concentration is not a major risk factor for milk fever and that dietary strong cations, especially K, induce metabolic alkalosis in the prepartum dairy cow, which reduces the ability of the cow to maintain Ca homeostasis.

Animals↗
PubMed1997

Physiological changes at parturition and their relationship to metabolic disorders.

Most of the metabolic diseases of dairy cows-milk fever, ketosis, retained placenta, and displacement of the abomasum-occur within the first 2 wk of lactation. The etiology of many of those metabolic diseases that are not clinically apparent during the first 2 wk of lactation, such as laminitis, can be traced back to insults that occurred during early lactation. In addition to metabolic disease, the overwhelming majority of infectious disease, in particular mastitis, becomes clinically apparent during the first 2 wk of lactation. Three basic physiological functions must be maintained during the periparturient period if disease is to be avoided: adaptation of the rumen to lactation diets that are high in energy density, maintenance of normocalcemia, and maintenance of a strong immune system. The incidence of both metabolic and infectious diseases is greatly increased whenever one or more of these physiological functions are impaired. This paper discusses the etiological role of each of these factors in the development of common diseases encountered during the periparturient period.

Animals↗
PubMed1997

Strategies for preventing milk fever in dairy cattle.

Milk fever is a complex metabolic disorder that occurs at the onset of lactation. Clinical symptoms of this disease include inappetence, tetany, inhibition of urination and defecation, lateral recumbency, and eventual coma and death if left untreated. The hallmark of this disease is severe hypocalcemia, which probably accounts for most of the clinical signs associated with a milk fever episode. Several factors have been consistently associated with increased incidence of milk fever, including parturition and initiation of lactation, advancing age, breed, and diet. Of the various methods used in attempts to control the disease, the most progress has been made in dietary management. Until recently, most attention has focused on manipulating the levels of dietary calcium to control milk fever incidence; results, however, have been inconsistent, except for those diets containing very low (8 to 10 g/d) concentrations of Ca. During the past decade, there has been renewed interest and research in the use of dietary anions (Cl- and SO4(2-) in controlling milk fever. An outgrowth of this research has been the surprising realization that dietary K is significant (perhaps more significant than Ca) in determining the susceptibility of dairy cows to milk fever. This knowledge has expanded the understanding of the pathogenesis of milk fever and has focused attention on research designed to study methods for neutralizing the detrimental effects of dietary K excess on periparturient animal health. This report discusses various practical strategies and potential research areas for managing the dietary forage components to minimize the effects of K on milk fever incidence.

Animals↗
PubMed1997

Comparison of oral sodium compounds for the correction of acidosis.

Three Na compounds were tested to determine which was best able to treat metabolic acidosis in dairy cows. Metabolic acidosis was induced in test cows by feeding a diet that was high in anions for 7 d before the administration of treatment on d 8. The orally administered treatments were equivalent amounts of Na in the form of NaCl (208.6 g), NaHCO3 (300 g), or Na propionate (343 g). The initiation of oral treatment was designated as time 0, and blood samples were taken 15 min before treatment, immediately before treatment, and 15, 30, 45, 60, 90, 120, 180, 240, 300, and 360 min after treatment. Before treatment, all cows were in a state of metabolic acidosis as was evidenced by low blood pH, low HCO3 concentrations, and high plasma Cl concentrations. After treatment, blood pH and HCO3 were markedly higher for cows receiving NaHCO3 and Na propionate but not for cows receiving NaCl. We concluded that orally administered NaHCO3 and Na propionate were equally effective in correcting the acid-base balance of blood, as was predicted by the strong ion difference theory of acid-base physiology. Sodium propionate may be considered a more effective treatment of metabolic acidosis in diseases such as ketosis because the added propionate can serve as a source of glucose for the cow.

Acidosis↗
PubMed1997

Effects of replacement of native fat in colostrum and milk with coconut oil on fat-soluble vitamins in serum and immune function in calves.

Fat-soluble vitamins and their metabolites modulate immune function in a variety of animal species. The objective of the present study was to determine the role of fat-soluble vitamins in colostrum and milk in the development of specific aspects of immune function in the calf during the 1st wk postpartum. During this period, control calves (n = 6) were fed normal colostrum and milk, and calves in the treatment group (n = 6) were fed skimmed colostrum and skimmed milk supplemented with coconut oil. Treated calves did not experience the progressive increase in concentrations of retinol, beta-carotene, alpha-tocopherol, 1,25-dihydroxyvitamin D, or retinoic acids in serum that was observed in control calves. Acquisition of passive immunity, which is indicated by concentrations of immunoglobulin G1 in serum, was unaffected by treatment. Composition and functional capacities of populations of blood mononuclear leukocytes that were collected from birth to 7 d postpartum were also unaffected by treatment. Major changes in the function and composition of mononuclear leukocyte populations from all calves occurred during the experimental period and were unrelated to the concentrations of fat-soluble vitamins in serum. Populations of blood mononuclear leukocytes from calves were functionally hyporesponsive and compositionally different from populations of blood mononuclear leukocytes from adult nongravid cows. These differences likely reflected the immaturity of the immune system of the neonatal calf and may contribute to the increased susceptibility of the calf to infectious disease.

Aging↗
PubMed1997

Reactivity and phenotype of mononuclear leukocytes from nongravid heifers after in vitro exposure to 9,13-di-cis-retinoic acid.

The predominant isomer of retinoic acid in the plasma of dairy cows during the periparturient period is 9,13-di-cis-retinoic acid. Because retinoic acids influence the activity of cells in a variety of tissues, including the immune system, the potential for this isomer to modulate the bovine immune system during the periparturient period must be considered. The present study examined the in vitro effects of 9,13-di-cis-retinoic acid on the reactivity and phenotype of blood mononuclear leukocytes from nongravid Holstein heifers that were sensitized to antigens and that had naturally low plasma concentrations of 9,13-di-cis-retinoic acid. In this system, 9,13-di-cis-retinoic acid, approximating the highest plasma concentrations occurring in vivo during the periparturient period, had no effect on DNA synthesis, secretion of interleukin-2 or interferon-gamma, or secretion of immunoglobulin by unstimulated cultures or cultures stimulated by mitogen (pokeweed mitogen) or antigen (ovalbumin). The composition of unstimulated and stimulated mononuclear leukocyte populations, based on percentages of specific cell types, was unaffected by 9,13-di-cis-retinoic acid at the physiologic concentration of 10(-8) M. 9,13-di-cis-Retinoic acid did not affect the actual number of cells in unstimulated cultures and cultures stimulated by antigen but did cause a moderate reduction in the number of cells, primarily CD4+ lymphocytes, in cultures stimulated by mitogen. Overall, these results suggest that the elevated concentration of 9,13-di-cis-retinoic acid in maternal plasma may have a negligible effect on the reactivity and phenotype of cells constituting the circulating mononuclear leukocyte population.

Animals↗
PubMed1996

A 20-epi side chain restores growth-regulatory and transcriptional activities of an A ring-modified hybrid analog of 1 alpha, 25-dihydroxyvitamin D3 without increasing its affinity to the vitamin D receptor.

1 alpha-hydroxymethyl-25-hydroxyvitamin D3 and 1 beta-hydroxymethyl -3 alpha,25-hydroxyvitamin D3, two analogs with modifications restricted to the A ring, bind poorly to vitamin D receptor (VDR). The effective doses required for 50% of maximal binding activity (ED50) are 7 x 10(-7) M for the former and 8 x 10(-8) M for the latter, and the ED50 for their growth-inhibitory activities is greater than 10(-6) M. Unexpectedly, a hybrid analog with 20-epi configuration at its side chain and a 1 beta-hydroxymethyl group but not a 1 alpha-hydroxymethyl group inhibits malignant cell growth with an ED50 of 7 x 10(-9) M. To determine if the restored biological activity of the hybrid analog is associated with better binding to VDR, we performed competitive binding assays in vitro with calf thymus VDR and in vivo with recombinant human VDR. We found that the 20 epi side chain reduced the affinity of the 1 beta- and the 1 alpha-hydroxymethyl hybrid analogs for VDR in vitro and in vivo fourfold to tenfold. To determine whether the 1 beta-hydroxymethyl analogs induced a VDR-mediated transcription, we tested the induction of reporter gene expression through the osteocalcin vitamin D response element (VDRE) in ROS 17/2.8 cells and the induction of binding activity of VDR to VDRE in COS-1 cells. We found that the ED50 for transcriptional activity of 1 beta-hydroxymethyl-3 alpha,25-hydroxyvitamin D3 was greater than 10(-6) M, but its 1 alpha diastereomer had barely detectable transcriptional activity. The 20-epi side chain preferentially increased the transcriptional activity of the 1 beta-hydroxymethyl hybrid analog to an ED50 of 10(-8) M, but the 1 alpha-hydroxymethyl hybrid analog remained inactive. To confirm that this transcriptional activity was dependent on the VDR, we repeated the assay in VDR-negative CV-1 cells and compared ligand-dependent expression of the VDRE/growth hormone reporter in the presence of either wild-type or transcriptionally inactive mutant VDR expression vectors. Transcription was induced by the 1 beta-hydroxymethyl compounds only in the presence of wild-type VDR. Thus, we conclude that it is possible, by adding a 20 epi side chain, to restore growth-inhibitory and VDR-mediated transcriptional activities without increasing binding to the VDR of A ring-modified analogs.

Animals↗
PubMed1996

Vitamin D receptor interactions with the murine osteopontin response element.

The nature of the DNA binding interactions of the human vitamin D receptor (hVDR) with the murine osteopontin vitamin D response element (mOP VDRE) was examined. Both recombinant hVDR and human retinoid X receptor beta (hRXRbeta) proteins were obtained from baculovirus-infected Sf9 insect cells. Mixing extracts of the two recombinant proteins resulted in the strong, specific formation of a slower migrating complex in the electrophoretic mobility shift assay. Crude extracts of the expressed hVDR alone were also capable of binding with high affinity to the mOP sequence, and this binding was enhanced in the presence of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). Competition experiments confirmed the specificity of this interaction and revealed that the human osteocalcin VDRE was a poor competitor for this binding. Ethylation interference footprint analyses of hVDR/hRXRbeta and hVDR complexes revealed only subtle differences in how these two different VDR-containing complexes interacted with the mOP VDRE. The footprints displayed contact points in both halves of the direct repeat format, confirming the dimeric and major groove interactions of both types of complexes. DNA affinity chromatography of labelled hVDR extracts revealed a peak eluting at ca. 290 mM KC1 that was capable of rebinding to the mOP sequence in gel shift experiments. Ultraviolet (UV) light-crosslinking experiments of hVDR extracts alone to radiolabelled DNA were consistent with the existence of a homodimeric hVDR interaction. Additionally, these experiments confirmed the direct interaction of a hVDR/hRXRbeta heterodimer when mixed extracts were utilized. From these results we infer that homodimers of the hVDR which respond with enhanced DNA binding to particular vitamin D response elements when exposed to 1,25-(OH)2D3 are possible. This may be of functional significance when RXR proteins are limiting or RXR ligand is present within a cell.

Animals↗
PubMed1996

Task complexity in emergency medical care and its implications for team coordination. LOTAS Group. Level One Trauma Anesthesia Simulation.

To elicit components of task complexity in emergency medical care, a study was conducted to contrast one medical procedure with two levels of task urgency in trauma patient resuscitation. Videotapes of actual resuscitation were reviewed to extract task characteristics of the procedure. Two levels of urgency were compared in the following areas: patient status, technical difficulty of tasks, the amount of available patient monitoring information, and the pace of work. Four components of task complexity in emergency medical care were identified: multiple and concurrent task, uncertainty, changing plans, and compressed work procedures and high workload. These components of task complexity pose challenges to team functions and can lead to problems in team coordination, such as conflicts in goals, tasks, and access to the patient. Training to increase explicit communications and improvements in the design of work procedures are necessary in order to meet the challenges of task complexity.

Baltimore↗