Early Outcomes of a Universal Femoral Component with an Ultracongruent Insert.

INTRODUCTION: A primary total knee arthroplasty (TKA) system was introduced with a modern universal femoral design with a wide range of size and constraint options to accommodate a variety of patient anatomy, while incorporating streamlined instrumentation for maximum operating room efficiency and economy. The purpose of this study is to review the early clinical outcomes and survivorship at minimum two-year follow up with this knee system. MATERIALS AND METHODS: From September 2015 to December 2019, 797 patients (1004 knees) underwent primary total knee arthroplasty (TKA) at our center with the TJO Klassic® Complete Primary Knee System (Total Joint Orthopedics Inc., Salt Lake City, Utah) with ultracongruent bearings and were available for study with minimum two-year follow up. All office and hospital records were reviewed for patient demographics, preoperative and postoperative clinical assessments, including range of motion, Knee Society Scores (KSS), University of California at Los Angeles (UCLA) activity scales, complications, and reoperations. RESULTS: Mean follow up was 3.1 years (range, 2-6; standard deviation [SD] ±1.0). There were 471 female patients (59%) and 326 male patients (41%). Mean age at surgery was 69.3 years and mean body mass index was 32.9kg/m2. An all-polyethylene tibial component was used in 305 knees (30.4%) while a modular titanium tibial baseplate with polyethylene insert was used in 699 (69.6%). The patella was left unresurfaced in 381 knees (37.9%). KS scores, including pain component, clinical, and functional, as well as UCLA scores, all improved significantly (p<0.001). Two patients (3 knees) underwent revision. One patient required two-staged revision for treatment of infection in both knees, and one patient required patellar revision for aseptic loosening. Kaplan-Meier survival at 6.2 years was 98.4% (95% CI: ±0.97%) to endpoint of revision of any part for any cause and 99.6% (95% CI: ±0.36%) to endpoint of aseptic revision. CONCLUSIONS: At early minimum two-year follow up, this modern universal complete knee system used with ultracongruent bearings demonstrates excellent clinical outcomes and survival.

Age of Acquisition Modulates Alpha Power During Bilingual Speech Comprehension in Noise.

Research on bilingualism has grown exponentially in recent years. However, the comprehension of speech in noise, given the ubiquity of both bilingualism and noisy environments, has seen only limited focus. Electroencephalogram (EEG) studies in monolinguals show an increase in alpha power when listening to speech in noise, which, in the theoretical context where alpha power indexes attentional control, is thought to reflect an increase in attentional demands. In the current study, English/French bilinguals with similar second language (L2) proficiency and who varied in terms of age of L2 acquisition (AoA) from 0 (simultaneous bilinguals) to 15 years completed a speech perception in noise task. Participants were required to identify the final word of high and low semantically constrained auditory sentences such as "Stir your coffee with a spoon" vs. "Bob could have known about the spoon" in both of their languages and in both noise (multi-talker babble) and quiet during electrophysiological recording. We examined the effects of language, AoA, semantic constraint, and listening condition on participants' induced alpha power during speech comprehension. Our results show an increase in alpha power when participants were listening in their L2, suggesting that listening in an L2 requires additional attentional control compared to the first language, particularly early in processing during word identification. Additionally, despite similar proficiency across participants, our results suggest that under difficult processing demands, AoA modulates the amount of attention required to process the second language.

Electrophysiology reflects the influence of discourse context on auditory semantic processing in bilinguals.

Most language experiences take place at the level of multiple sentences. However, previous studies of second language (L2) comprehension have typically focused on lexical- and sentence-level processing. Our study addresses this gap by examining auditory discourse comprehension in 32 English/French bilinguals. We tested the prediction of the noisy channel model (Futrell & Gibson, 2017) that bilinguals will rely more on top-down, discourse-level cues in L2 because these are common across languages, as opposed to the language-specific associations of an often weaker L2. We further hypothesized that these effects could be influenced by individual differences, such that participants with lower L2 proficiency or working memory would have more difficulty building and maintaining discourse context. Specifically, we measured the N400 response, an index of automatic semantic processing. Participants heard three-sentence stories with prime and target words in the final sentence whose lexical association was manipulated, as was the congruence of the target with the preceding discourse. Overall, our results support the noisy channel model of language comprehension in a sample of highly proficient bilinguals. We observed larger N400 effects of discourse congruence than lexical association, and the difference between these 2 conditions was greater in the L2 than in the L1. Additionally, the effects of lexical association were limited to the L1 and predicted by individual differences in language dominance but not working memory. These findings suggest that bilinguals do indeed make greater use of top-down, supralinguistic information in their L2 compared with their L1. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A longitudinal investigation of structural brain changes during second language learning.

Few studies have examined the time course of second language (L2) induced neuroplasticity or how individual differences may be associated with brain changes. The current longitudinal structural magnetic resonance imaging study examined changes in cortical thickness (CT) and gray matter volume (GMV) across two semesters of L2 Spanish classroom learning. Learners' lexical processing was assessed via a language decision task containing English and Spanish words. Our findings indicated that (1) CT increased in the left anterior cingulate cortex (ACC) and right middle temporal gyrus (MTG) after L2 learning, (2) CT in the right MTG increased in individuals who were better able to discriminate between native language and L2 words, and (3) CT in the left ACC was correlated with functional connectivity between the ACC and MTG. These findings indicate that L2 lexical development is associated with functional and structural changes in brain regions important for cognitive control and semantic processing.

Reversal of overdose on fentanyl being illicitly sold as heroin with naloxone nasal spray: A case report.

BACKGROUND: This is a case report describing a reversal of fentanyl overdose with naloxone nasal spray. The patient was not aware that he overdosed on fentanyl being sold as heroin. METHODS: The Veterans Health Administration (VHA) has implemented an initiative to provide education for veterans, their families, friends and significant others about opioid overdose and use of naloxone reversal kits. The Atlanta VA Medical Center adopted this program to reduce the risk of opioid overdose in high risk patients. RESULTS: Over the past year, we provided educational sessions for 63 veterans and their families. We also prescribed 41 naloxone kits. We have received three reports of opioid overdose reversal with use of naloxone kits prescribed by the Atlanta VA Medical Center. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The authors recommend that public health administrators and policy makers advocate for the implementation of these programs to reduce the rising number of overdose death in the United States and worldwide.

Second language lexical development and cognitive control: A longitudinal fMRI study.

In this paper we report a longitudinal functional magnetic resonance imaging (fMRI) study that tested contrasting predictions about the time course of cognitive control in second language (L2) acquisition. We examined the neural correlates of lexical processing in L2 learners twice over the course of one academic year. Specifically, while in the scanner, participants were asked to judge the language membership of unambiguous first and second language words, as well as interlingual homographs. Our ROI and connectivity analyses reveal that with increased exposure to the L2, overall activation in control areas such as the anterior cingulate cortex decrease while connectivity with semantic processing regions such as the middle temporal gyrus increase. These results suggest that cognitive control is more important initially in L2 acquisition, and have significant implications for understanding developmental and neurocognitive models of second language lexical processing.

Cognitive control, cognitive reserve, and memory in the aging bilingual brain.

In recent years bilingualism has been linked to both advantages in executive control and positive impacts on aging. Such positive cognitive effects of bilingualism have been attributed to the increased need for language control during bilingual processing and increased cognitive reserve, respectively. However, a mechanistic explanation of how bilingual experience contributes to cognitive reserve is still lacking. The current paper proposes a new focus on bilingual memory as an avenue to explore the relationship between executive control and cognitive reserve. We argue that this focus will enhance our understanding of the functional and structural neural mechanisms underlying bilingualism-induced cognitive effects. With this perspective we discuss and integrate recent cognitive and neuroimaging work on bilingual advantage, and suggest an account that links cognitive control, cognitive reserve, and brain reserve in bilingual aging and memory.

HIV-1 Nef mobilizes lipid rafts in macrophages through a pathway that competes with ABCA1-dependent cholesterol efflux.

HIV infection, through the actions of viral accessory protein Nef, impairs activity of cholesterol transporter ABCA1, inhibiting cholesterol efflux from macrophages and elevating the risk of atherosclerosis. Nef also induces lipid raft formation. In this study, we demonstrate that these activities are tightly linked and affect macrophage function and HIV replication. Nef stimulated lipid raft formation in macrophage cell line RAW 264.7, and lipid rafts were also mobilized in HIV-1-infected human monocyte-derived macrophages. Nef-mediated transfer of cholesterol to lipid rafts competed with the ABCA1-dependent pathway of cholesterol efflux, and pharmacological inhibition of ABCA1 functionality or suppression of ABCA1 expression by RNAi increased Nef-dependent delivery of cholesterol to lipid rafts. Nef reduced cell-surface accessibility of ABCA1 and induced ABCA1 catabolism via the lysosomal pathway. Despite increasing the abundance of lipid rafts, expression of Nef impaired phagocytic functions of macrophages. The infectivity of the virus produced in natural target cells of HIV-1 negatively correlated with the level of ABCA1. These findings demonstrate that Nef-dependent inhibition of ABCA1 is an essential component of the viral replication strategy and underscore the role of ABCA1 as an innate anti-HIV factor.

Mutation of the ATP cassette binding transporter A1 (ABCA1) C-terminus disrupts HIV-1 Nef binding but does not block the Nef enhancement of ABCA1 protein degradation.

HIV-1 infection and antiretroviral therapy are associated with a dyslipidemia marked by low levels of high-density lipoprotein and increased cardiovascular disease, but it is unclear whether virion replication plays a causative role in these changes. The HIV-1 Nef protein can impair ATP cassette binding transporter A1 (ABCA1) cholesterol efflux from macrophages, a potentially pro-atherosclerotic effect. This viral inhibition of efflux was correlated with a direct interaction between ABCA1 and Nef. Here, we defined the ABCA1 domain required for the Nef-ABCA1 protein-protein interaction and determined whether this interaction mediates the ability of Nef to downregulate ABCA1. Nef expressed in HEK 293 cells strongly inhibited ABCA1 efflux and protein levels but did not alter levels of cMIR, another transmembrane protein. Analysis of a panel of ABCA1 C-terminal mutants showed Nef binding required the ABCA1 C-terminal amino acids between positions 2225 and 2231. However, the binding of Nef to ABCA1 was not required for inhibition because the C-terminal ABCA1 mutants that did not bind Nef were still downregulated by Nef. Given this discordance, the mechanism of downregulation was investigated and was found to involve the acceleration of ABCA1 protein degradation but did not to depend upon the ABCA1 PEST sequence, which mediates the calpain proteolysis of ABCA1. Furthermore, it did not associate with a Nef-dependent induction of signaling through the unfolded protein response but was significantly dependent upon proteasomal function and could act on an ABCA1 mutant that fails to exit the endoplasmic reticulum. In summary, we show that Nef downregulates ABCA1 function by a post-translational mechanism that stimulates ABCA1 degradation but does not require the ability of Nef to bind ABCA1.

Circulating Nef induces dyslipidemia in simian immunodeficiency virus-infected macaques by suppressing cholesterol efflux.

Human immunodeficiency virus (HIV) infection and subsequent antiretroviral therapy have been associated with an increased incidence of dyslipidemia and cardiovascular disease and has been shown to suppress cholesterol efflux from virus-infected macrophages by inducing Nef-dependent down-regulation of adenosine triphosphate-binding cassette transporter A1 (ABCA1). Here, the simian immunodeficiency virus (SIV)-infected macaque model was used to examine the consequences and mechanisms involved. SIV infection drove a significant remodeling of high-density lipoprotein profiles, suggesting that systemic inhibition of the ABCA1-dependent reverse cholesterol transport pathway occurred. The ABCA1 cholesterol transporter was significantly down-regulated in the livers of the SIV-infected macaques, and the viral protein Nef could be detected in the livers as well as in the plasma of infected animals. Extracellular myristoylated HIV Nef inhibited cholesterol efflux from macrophages and hepatocytes. Moreover, serum samples from SIV-infected macaques also suppressed cholesterol efflux in a Nef-dependent fashion. These results indicate that SIV infection is a significant contributor to primary dyslipidemia, likely through the ability of Nef to suppress ABCA1-dependent reverse cholesterol transport.

Stimulation of the liver X receptor pathway inhibits HIV-1 replication via induction of ATP-binding cassette transporter A1.

Cholesterol plays an important role in the HIV life cycle, and infectivity of cholesterol-depleted HIV virions is significantly impaired. Recently, we demonstrated that HIV-1, via its protein Nef, inhibits the activity of the major cellular cholesterol transporter ATP binding cassette transporter A1 (ABCA1), suggesting that the virus may use this mechanism to get access to cellular cholesterol. In this study, we investigated the effect on HIV infection of a synthetic liver X receptor (LXR) ligand, N-(2,2,2-trifluoro-ethyl)-N-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-benzenesulfonamide (TO-901317), which is a potent stimulator of ABCA1 expression. We demonstrate that TO-901317 restores cholesterol efflux from HIV-infected T lymphocytes and macrophages. TO-901317 potently suppressed HIV-1 replication in both cell types and inhibited HIV-1 replication in ex vivo cultured lymphoid tissue and in RAG-hu mice infected in vivo. This anti-HIV activity was dependent on ABCA1, because the effect of the drug was significantly reduced in ABCA1-defective T cells from a patient with Tangier disease, and RNA interference-mediated inhibition of ABCA1 expression eliminated the effect of TO-901317 on HIV-1 replication. TO-901317-mediated inhibition of HIV replication was due to reduced virus production and reduced infectivity of produced virions. The infectivity defect was in part due to reduced fusion activity of the virions, which was directly linked to reduced viral cholesterol. These results describe a novel approach to inhibiting HIV infection by stimulating ABCA1 expression.

Variation in fitness of the longhorned beetle, Dectes texanus, as a function of host plant.

Dectes texanus LeConte (Coleoptera: Cerambycidae) has become a serious pest of two different crops in the American Midwest, sunflower, Helianthus annuus L. and soybean, Glycines max (L.). Laboratory and field studies were used to compare the effects of these two host plants on D. texanus life history and behavior. Insects from soybean were 40-60% smaller than those from sunflower and larval weight at collection was strongly correlated with survival to adulthood, whereas it was not in sunflower, suggesting that body size was more limiting to immature survival in soybean. Pupal weights increased more rapidly with increasing stem diameter in soybean than in sunflower and the correlation was stronger, indicating that body size was more limited by plant size in soybean. Adults collected as larvae from soybean had shorter longevities when starved, fed soybean, or fed an alternating diet of soybean and cultivated sunflower, than did those collected from sunflower, suggesting a negative larval legacy of soybean on adult fitness. Adult beetles that developed in soybean lived longer when fed soybean than when starved, but an adult diet of sunflower doubled longevity compared to soybean for beetles that developed in sunflower, and tripled it for those that developed in soybean. An adult diet of wild H. annuus yielded survivorship equivalent to cultivated H. annuus in one trial, and slightly lower in another. Larval host plant did not influence the numbers of ovipunctures or eggs laid by females in field trials, but adult diet did. Sunflower-fed females punctured more, and laid more eggs, on sunflowers than on soybeans in field cages and the reverse trend was evident, but not significant, in soybean-fed females. It can be concluded that H. annuus is a superior food source to G. max for both larval and adult D. texanus, and that wild sunflowers may represent a valuable food for adults during the pre-reproductive period, prior to invasion of soybean fields, even though they rarely host larvae. We also showed that stable isotope ratios of N can be used to distinguish the larval host plant of beetles regardless of their adult diet.

Antiretroviral compounds and cholesterol efflux from macrophages.

OBJECTIVE: HIV infection is associated with elevated risk of cardiovascular disease. The effect of antiretroviral drugs on metabolism of atherogenic very low and low density lipoproteins is well studied, but a possible effect of these drugs on reverse cholesterol transport is still unclear. The objective of this study was to assess the effect of various classes of anti-HIV drugs on cellular cholesterol efflux. METHODS: The effect of pharmacological concentrations of seven commonly used antiretroviral compounds, Stavudine, Efavirenz, Nevirapine, Lopinavir, Amprenavir, Nelfinavir and Ritonavir, on cholesterol efflux from RAW 264.7 mouse macrophages and human monocyte-derived macrophages to apolipoprotein A-I and high density lipoprotein was tested. RESULTS: At high pharmacological concentration Nelfinavir and Ritonavir inhibited cholesterol efflux, while other compounds had no effect. However, the same concentrations of Nelfinavir and Ritonovir induced apoptosis, suggesting that the effect of these compounds on cholesterol efflux most likely resulted from their cytotoxicity. When tested in non-cytotoxic concentrations, Nelfinavir and Ritonavir did not affect cholesterol efflux from RAW 264.7 cells, human monocyte-derived macrophages, or human macrophages infected with HIV-1. CONCLUSIONS: We conclude that tested antiretroviral compounds do not have a specific effect on cholesterol efflux.

Enhancing apolipoprotein A-I-dependent cholesterol efflux elevates cholesterol export from macrophages in vivo.

Eight proteins potentially involved in cholesterol efflux [ABCA1, ABCG1, CYP27A1, phospholipid transfer protein (PLTP), scavenger receptor type BI (SR-BI), caveolin-1, cholesteryl ester transfer protein, and apolipoprotein A-I (apoA-I)] were overexpressed alone or in combination in RAW 264.7 macrophages. When apoA-I was used as an acceptor, overexpression of the combination of ABCA1, CYP27A1, PLTP, and SR-BI (Combination I) enhanced the efflux by 4.3-fold. It was established that the stimulation of efflux was due to increased abundance of ABCA1 and increased apoA-I binding to non-ABCA1 sites on macrophages. This combination caused only a small increase of the efflux to isolated HDL. When HDL was used as an acceptor, overexpression of caveolin-1 or a combination of caveolin-1 and SR-BI (Combination II) was the most active, doubling the efflux to HDL, without affecting the efflux to apoA-I. When tested in the in vivo mouse model of cholesterol efflux, overexpression of ABCA1 and Combination I elevated cholesterol export from macrophages to plasma, liver, and feces, whereas overexpression of caveolin-1 or Combination II did not have an effect. We conclude that pathways of cholesterol efflux using apoA-I as an acceptor make a predominant contribution to cholesterol export from macrophages in vivo.

Sunflowers as a trap crop for reducing soybean losses to the stalk borer Dectes texanus (Coleoptera: Cerambycidae).

Larvae of Dectes texanus LeConte cause significant losses to soybean production in the American High Plains by girdling the stalks of mature plants at their base, causing them to lodge. The authors demonstrated that cultivated sunflowers can reduce rates of D. texanus infestation in adjacent soybean fields because adult females prefer sunflower over soybean for feeding and oviposition. Since females do not avoid ovipositing in plants already containing their own eggs or those of conspecific females, sunflower plants can accumulate multiple eggs, and subsequent larval combat typically results in the survival of only one. In west central Kansas, planting one half of a center pivot irrigated field to sunflower in 2004 significantly reduced infestation of soybean plants in the other half of the field within 200 m of the crop border. Beyond 200 m from the sunflowers, the rate of soybean infestation increased significantly. Planting sunflowers in the non-irrigated corners of a center pivot irrigated soybean field in 2005 reduced D. texanus infestation of soybeans by 65% compared with a control field without adjacent sunflowers. Surrounding a 0.33 ha soybean field with six rows of sunflowers in 2006 reduced soybean infestation to < 5% of plants, compared with 96% of sunflower plants. These results reveal that sunflowers can reduce D. texanus infestation in adjacent soybeans by acting as an 'ovipositional sink'. Further research is warranted to determine the optimum crop area proportions and spatial configurations that will maximize the efficacy of a sunflower trap crop to reduce soybean losses due to D. texanus-induced lodging.

Impact of the stem borer, Dectes texanus, on yield of the cultivated sunflower, Helianthus annuus.

Foliar and soil-drench insecticide treatments were used in attempts to manipulate infestation of cultivated sunflower plants, Helianthus annuus LeConte (Asterales: Asteraceae) by Dectes texanus LeConte, (Coleoptera: Cerambycidae) a serious pest of sunflowers in the High Plains of the USA. Seed yields were assessed on a per-plant basis for both oilseed and confection type sunflower hybrids in two years. Both insecticide treatments (foliar ë-cyhalothrin and soil-drench carbofuran) improved yield of oilseed sunflowers in 2004, but not in 2005. Yield of confection hybrids was improved by a systemic fungicide (thiophanate methyl) in 2005, but insecticides did not improve yield in either year. Both insecticide treatments gave good control of various stalk-boring insects such as Cylindrocopturus adspersus (Coleoptera: Curculionidae), Mordellistena sp. (Coleoptera: Mordellidae), and Pelochrista womanana (Lepidoptera: Tortricidae), but neither gave better than 50% control of D. texanus. Plants were sorted according to the presence or absence of D. texanus larvae and no reduction was found in total seed weight, seed size, or oil content as a result of infestation. However, mature larvae of D. texanus girdle stalks at the base in preparation for overwintering, a behavior that reduced stalk breakage force by 34-40%, leading to yield losses through lodging. At harvest in 2005, there were differences between cultivars and among treatments in the proportions of D. texanus larvae that had girdled their plants at harvest. It was concluded that further research aimed at reducing crop losses to D. texanus should focus on means of delaying stalk desiccation and/or deterioration, factors that appear to trigger girdling behavior.

A cell-detachment solution can reduce background staining in the ELISPOT assay.

Enzyme-linked immunospot (ELISPOT) assays are widely used as a technique that allows determining the frequency of cytokine-releasing cells. Colored spots appear at the sites of cells releasing cytokines, with each individual spot representing a single cytokine-releasing cell. Porous membranes are used in ELISPOT plates to provide support for growing cells, thus making it difficult to remove them by washing. Cells that have adhered to the membrane may be stained nonspecifically, producing a background and then counted as specific spots. We have tested a cell detachment reagent, Accumax, and found that it may be used to remove a large number of cells adhered to the microplate membranes. Accumax was tested in 16 different ELISPOT assays, including human interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8, IL-13, IL-1beta, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha; mouse IL-4, IL-6, IFN-gamma, and TNF-alpha; rat IL-2 and IFN-gamma; and canine IFN-gamma. Accumax was found to be compatible with human IL-13, IL-1beta, IL-2, IL-4, IL-5, and IL-8 and mouse IL-4, IL-6, and TNF-alpha ELISPOT assays, allowing one to remove a large number of adhered cells without hindering ELISPOT assay performance. However, Accumax was incompatible with human IFN-gamma, mouse IFN-gamma, canine IFN-gamma, and rat IFN-gamma ELISPOT assays because Accumax reduced the intensity of staining and the number of spots formed.

Simultaneous detection of multiple cytokines in ELISPOT assays.

Living in the era of multiplex detection systems, it appears attractive to develop enzyme-linked immunospot (ELISPOT) assays for the detection of more than one cytokine released by the same cell. However, despite technical simplicity in building such an assay, several factors have to be considered when designing multiplex ELISPOT assays. We have used four capture antibodies (hIFN-gamma, hIL-2, hIL-4, and hTNF-alpha) either in combination or individually to coat polyvinylidene difluoride membrane-backed Millipore 96-well plates. Several cell stimulations were also used, including Concanavalin A, Phorbol Myristate Acetate (PMA) and calcium ionophore (CaI), phytohemagglutinin, CD3e, and lipopolysaccharide. Biotinylated antibodies were used either individually or combined together to detect secreted cytokines. We have found that when plates were coated with all four capture antibodies and captured cytokines were detected using either one detection antibody or all four detection antibodies combined together, fewer spots could be seen when compared with a plate coated with a single capture antibody followed by using its matched detection antibody counterpart. Interestingly, negative interferences between antibodies were less profound when detection antibodies rather than capture antibodies were mixed together.

Betamethasone pharmacokinetics after two prodrug formulations in sheep: implications for antenatal corticosteroid use.

Maternal administration of betamethasone to enhance fetal lung maturation for women who threaten preterm labor is common clinical practice. However, recommendations regarding the choice of betamethasone formulations for perinatal use are vague. The disposition of betamethasone from two commonly used antenatal formulations is poorly understood. We therefore designed a study to capture the true pharmacokinetic profiles of betamethasone from these fast acting and dual-release formulations. Betamethasone in sheep plasma was measured by a newly designed, highly sensitive liquid chromatography/tandem mass spectrometry assay after intramuscular injection (n = 4) of 0.25 mg/kg betamethasone phosphate and 0.5 mg/kg betamethasone phosphate/acetate formulations. Compartmental modeling was performed using the ADAPT II program. Betamethasone pharmacokinetics could be captured for 24 h for the phosphate and for 5 days for the phosphate/acetate formulations. The phosphate formulation profile had the appearance of a traditional Bateman function with a terminal half-life of 4 h, whereas the phosphate/acetate formulation produced a biexponential decline with a terminal half-life of 14 h. The latter is much longer than is commonly reported and has been missed in the literature due to assay limitations. Extrapolations to humans indicate that although both formulations might have similar therapeutic indices, the dual formulation might be associated with a lower safety profile. In light of this newly identified long terminal half-life for the betamethasone dual formulation, dosing practices for betamethasone in pregnancy need to be reassessed.