Pharmacokinetics of Tranexamic Acid (TXA) Delivered by Expeditious Routes in a Swine Model of Polytrauma and Hemorrhagic Shock.

OBJECTIVE: Hemorrhage is the leading cause of preventable death in civilian trauma centers and on the battlefield. One of the emerging treatment options for hemorrhage in austere environments is tranexamic acid (TXA). However, the landscape is not amenable to the current delivery standard. This study compared the pharmacokinetics of TXA via a standard 10-minute intravenous infusion (IV infusion), intravenous rapid push over 10 s (IV push), and intramuscular injection (IM) in a swine polytrauma and hemorrhagic shock model (trauma group) compared to uninjured controls (control group). METHODS: Thirty swine were randomized to the trauma or control group. Following anesthesia, the trauma group experienced a simulated blast injury and 40% controlled hemorrhage. Subjects in both groups were then randomized to receive 1 g/10 mL TXA via IV infusion, IV push, or IM. Animals were monitored for four hours with serial blood sampling. Serum TXA concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS) and analyzed. RESULTS: The time to maximum TXA concentration (Tmax) was not affected by trauma in IV infusion or IV push, but was affected in the IM administration with Tmax significantly slower than the control group (p = 0.016). The minimum effective serum concentration of TXA (Ceff, 10 µg/mL) was reached in less than one minute with IV infusion and instantaneously with IV push. Despite lower bioavailability, the time to reach Ceff (Teff) was achieved via IM administration in less than 10 min for both groups (6.4 min trauma vs. 2.1 min control). CONCLUSIONS: In austere prehospital environments, an alternative to intravenous infusion of a life-saving medication is desired. Administration of TXA via all three methods reached the level needed to cause substantial inhibition of fibrinolysis within 10 min. The IV push method showed similar pharmacokinetics to IV infusion of TXA but can be delivered quickly without sacrificing an access site for 10 min.

Socio-ecologic Correlates of HIV/AIDS-Related Sexual Risk Behavior of African American Emerging Adults.

There is growing evidence showing that patterns of individual sexual risk behaviors are insufficient in explaining the disproportionate HIV/AIDS burden borne by African Americans. Instead, dynamic features of social, economic, political, and geographic contexts play a more determining role. However, not enough studies have examined the impact of multi-level factors including neighborhood-level influences on HIV/AIDS sexual risk among African American emerging adults using a socio-ecologic perspective. Anchored on the socio-ecologic framework, this study examines the collective role of relevant socio-ecologic determinants of sexual risk-taking among African American emerging adults. Results from both bivariate and multivariate analyses revealed that individual and neighborhood-level variables were significantly associated with sexual risk in our study population partially confirming the hypothesis of the study. Male gender, educational attainment, and neighborhood social disorder were the strongest predictors of sexual risk. Our findings contribute to the vast literature on sexual risk behavior patterns of young adults, and increasing evidence demonstrating the role of contextual factors as stronger predictors of sexual risk and HIV infection among at-risk youth. Our findings, however, underscore the need for further research on the pathways of HIV socio-behavioral vulnerability in this demographic group.

A New Interpretation of Relative Importance on an Analysis of Per and Polyfluorinated Alkyl Substances (PFAS) Exposures on Bone Mineral Density.

BACKGROUND: The relative contribution of environmental contaminants is an important, and frequently unanswered, question in human or ecological risk assessments. This interpretation of relative importance allows determination of the overall effect of a set of variables relative to other variables on an adverse health outcome. There are no underlying assumptions of independence of variables. The tool developed and used here is specifically designed for studying the effects of mixtures of chemicals on a particular function of the human body. METHODS: We apply the approach to estimate the contributions of total exposure to six PFAS (perfluorodecanoic acid, perfluorohexane sulfonic acid, 2-(N-methyl-PFOSA) acetate, perfluorononanoic acid, perfluoroundecanoic acid and perfluoroundecanoic acid) to loss of bone mineral density relative to other factors related to risk of osteoporosis and bone fracture, using data from subjects who participated in the US National Health Examination and Nutrition Surveys (NHANES) of 2013-2014. RESULTS: PFAS exposures contribute to bone mineral density changes relative to the following variables: age, weight, height, vitamin D2 and D3, gender, race, sex hormone binding globulin, testosterone, and estradiol. CONCLUSION: We note significant alterations to bone mineral density among more highly exposed adults and significant differences in effects between men and women.

Hook effect in gestational trophoblastic disease: An emergency department case presentation.

Gestational trophoblastic disease is a process that affects ≈1 of 1000 pregnancies. If left untreated, this can progress to potentially life-threatening complications with malignancy such as choriocarcinoma.  The emergency physician must be aware of the presentation and complications of this disease process, including the difficulties in diagnosis.  In this case presentation, the authors discuss the presentation and diagnostic process of a patient in the emergency department as well as the phenomenon known as the hook effect, which may complicate the decision-making process.

Predicting Exposure to Perfluorinated Alkyl Substances (PFAS) among US Infants.

PFASs have been detected in nearly every serum sample collected over the last two decades from US adults as part of the National Health and Nutrition Examination Survey (NHANES) and are commonly found in other data sets from around the world. However, less is known about infant PFAS exposures, primarily because the collection of infant serum samples is less common and frequently avoided. Cord blood samples are often preferred for chemical exposure assessments because this is thought to provide a good representation of infant serum concentrations, at least at the time of birth. In this paper, we will provide a statistical and probabilistic analysis of what can be expected for infants living in the US using NHANES from 2007 to 2008, which contains a rare subset of infant data. Regulatory efforts that require estimation of exposures among the very youth can be challenging, both because of a lack of data in general and because variability among this most vulnerable population can be uncertain. We report that US infant exposures are extremely common and that serum concentrations remain fairly constant, despite infant growth rates and relatively high caloric and fluid intake, with the possible exception of PFOS. Infant serum PFOS concentrations between months 1 and 3 are consistently higher than at less than one month, even though healthy infants at 1 and 2 months weigh more than they did at birth. This suggests that the babies are exposed to greater concentrations of PFOS after birth or that excretion kinetics differ for this PFAS.

PFAS and Potential Adverse Effects on Bone and Adipose Tissue Through Interactions With PPARγ.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a widely dispersed, broad class of synthetic chemicals with diverse biological effects, including effects on adipose and bone differentiation. PFAS most commonly occur as mixtures and only rarely, if ever, as single environmental contaminants. This poses significant regulatory questions and a pronounced need for chemical risk assessments, analytical methods, and technological solutions to reduce the risk to public and environmental health. The effects of PFAS on biological systems may be complex. Each may have several molecular targets initiating multiple biochemical events leading to a number of different adverse outcomes. An exposure to mixtures or coexposures of PFAS complicates the picture further. This review illustrates how PFAS target peroxisome proliferator-activated receptors. Additionally, we describe how such activation leads to changes in cell differentiation and bone development that contributes to metabolic disorder and bone weakness. This discussion sheds light on the importance of seemingly modest outcomes observed in test animals and highlights why the most sensitive end points identified in some chemical risk assessments are significant from a public health perspective.

Predicting Long-Term Asbestos Prevalence in Human Lungs, Lymph Nodes, and Remote Organs from Short-Term Murine Experiments.

Inhalation of asbestos fibers leads to a suite of fatal diseases that can manifest years, if not decades, after cessation of exposure. The first phase of disease progression occurs as fibers are transported from point of entry in the lungs throughout the entire body. A mathematical model is developed for the disposition of non-chrysotile asbestos in the body and, except for exposure levels, is parameterized by published data on short-term rat experiments. Asbestos exposure in individual humans is determined by matching published long-term lung data for nine patients. The resulting model predicts transport of fibers within the lymphatic system and prevalence of fibers in lymph nodes for these patients with reasonable accuracy. Model predictions for remote organs are compared against published observations. The model consists of a system of globally stable differential equations, and a sensitivity analysis was conducted. The model indicates that fiber density in lymph nodes is correlated with total exposure, level times duration, no matter whether there is a long-term, low-level exposure or short-term, high-level exposure. The model predicts that levels of sequestered asbestos reach steady state within five years of cessation of exposure, a timeline previously not known. The model suggests that the time to steady state is short compared to onset of disease, and that delayed onset of related disease may be a function of chemical and biological processes not in this model.

Evaluation of Fetal Exposures to Metals and Metalloids through Meconium Analyses: A Review.

This paper surveys the existing scientific literature on metals concentrations in meconium. We examine some 32 papers that analyzed meconium for aluminum, arsenic, barium, calcium, chromium, copper, iron, lithium, magnesium, manganese, zinc, lead, mercury, manganese, molybdenum, nickel, phosphorus, lead, antimony, selenium, tin, vanadium, and zinc. Because of the lack of detail in the statistics it is not possible to do a rigorous meta-analysis. What stands out is that almost every study had subjects with seemingly large amounts of at least one of the metals. The significance of metals in meconium is not clear beyond an indication of exposure although some studies have correlated metals in meconium to a number of adverse outcomes. A number of outstanding questions have been identified that, if resolved, would greatly increase the utility of meconium analysis for assessment of long-term gestational metals exposures. Among these are questions of the developmental and long-term significance of metals detected in meconium, the kinetics and interactions among metals in maternal and fetal compartments and questions on best methods for meconium analyses.

More Than Just Torsion: An Unusual Case of Testicular Pain.

Testicular pain has a wide differential and the nonspecific presentation should be triaged rapidly for urgent diagnosis and treatment. Scrotal pyoceles are uncommon collections of purulent fluid between the visceral and parietal tunica vaginalis, usually secondary to acute epididymo-orchitis, intra-abdominal infection, or trauma. Epididymitis and epididymo-orchitis are generally secondary to sexually transmitted infections or urinary tract pathogens. Epidymo-orchitis can compromise the testicular blood supply, leading to a microinfarction and rupture through the tunica albuginea; inflammatory and infectious material then translocate into the tunica vaginalis leading to the formation of a pyocele. Ultrasonography is the preferred method of diagnostic imaging, which can show a classic "falling snow" sign, loculations, or gas. The treatment for a scrotal pyocele is pain control, fluid resuscitation, broad-spectrum antibiotics, and early urology/general surgery consultation. In such cases, Fournier gangrene (FG) should be clinically ruled out and the presence of signs of Fournier gangrene should be met with an urgent surgical consult.

A dynamical model of the transport of asbestos fibres in the human body.

We present a model for the transport of a single type of asbestos fibre through the human body. The model captures the transport modes that pertain particularly to the lungs and the mesothelium. Numerical solutions of the system follow observed movement in the body. We compare the accumulation of fibres in the lungs versus the mesothelium, and then we give analysis and results for various cases of exposure level and exposure time. Models, such as the one developed here, can give clues as to how asbestos fibres impact the body, and where to look for major impact.

Temporal patterns in perchlorate, thiocyanate, and iodide excretion in human milk.

BACKGROUND: Perchlorate and thiocyanate interfere with iodide uptake at the sodium-iodide symporter and are potential disruptors of thyroid hormone synthesis. Perchlorate is a common contaminant of water, food, and human milk. Although it is known that iodide undergoes significant diurnal variations in serum and urinary excretion, less is known about diurnal variations of milk iodide levels. OBJECTIVES: Variability in perchlorate and thiocyanate excretion in human milk has not been examined. Our objective was to determine variability of perchlorate, thiocyanate, and iodide in serially collected samples of human milk. METHODS: Ten lactating women were asked to collect six milk samples on each of 3 days. As an alternative, subjects were asked to collect as many milk samples as comfortably possible over 3 days. Samples were analyzed for perchlorate, iodide, and thiocyanate by ion chromatography coupled with mass spectrometry. RESULTS: Individual perchlorate, iodide, and thiocyanate levels varied significantly over time; there was also considerable variation among individuals. The iodide range, mean +/- SD, and median for all samples (n = 108) were 3.1-334 microg/L, 87.9 +/- 80.9 microg/L, and 55.2 microg/L, respectively. The range, mean +/- SD, and median of perchlorate in all samples (n = 147) were 0.5-39.5 microg/L, 5.8 +/- 6.2 microg/L, and 4.0 microg/L. The range, mean +/- SD, and median of thiocyanate in all samples (n = 117) were 0.4 -228.3 microg/L, 35.6 +/- 57.9 microg/L, and 5.6 microg/L. The data are not symmetrically distributed; the mean is higher than the median in all cases. CONCLUSIONS: Iodine intake may be inadequate in a significant fraction of this study population. Perchlorate and thiocyanate appear to be common in human milk. The role of these chemicals in reducing breast milk iodide is in need of further investigation.