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Objective: Polymorphisms in the genes for factor V (factor V Leiden), prothrombin, methylenetetrahydrofolate reductase, and angiotensin-converting enzyme have been associated with the occurrence of venous thrombosis. The objective of this study was to determine the relationships of these polymorphisms to thrombosis during pregnancy.Study Design: This case-control study included 41 case patients with venous thrombosis during pregnancy and 76 control subjects matched for hospital and for race (white vs black) who had a normal pregnancy.Results: Among white subjects, mutations in the genes for factor V and prothrombin were associated with increased risks of venous thrombosis during pregnancy (factor V: odds ratio, 18.3; 95% confidence interval, 2.7-432; P =.001; prothrombin: odds ratio infinity; 95% lower confidence limit, 1.7; P =.01). No black subject had either of these two mutations. For both black and white subjects the D/D genotype of the gene for angiotensin-converting enzyme entailed increased risk compared with the other genotypes (odds ratio, 2.7; 95% confidence interval, 1.2-6.3; P =.02). The polymorphism in the gene for methylenetetrahydrofolate reductase was unrelated to thrombosis during pregnancy among both blacks and whites.Conclusion: Women who had thrombotic complications during pregnancy demonstrated an increased prevalence of genetic mutations related to coagulation. The additional risk of thrombosis during pregnancy associated with such genetic mutations can be substantial. [ABSTRACT FROM AUTHOR]

Produced water (i.e., a mixture of returned injection fluids and geologic formation brines) represents the largest volumetric waste stream associated with petroleum production in the United States. As such, produced water has been the focus of intense study with emphasis on understanding the geologic origin of the fluids, environmental impacts of unintended or intentional release, disposal concerns, and their commodity (e.g., lithium) potential. However, produced water geochemistry from many active petroleum plays remain poorly understood leading to knowledge gaps associated with the origin of brine salinity and parameters (e.g., radium levels) that can impact treatment, disposal, and possible reuse. Here we evaluate the major ion geochemistry, radium concentrations, and stable water isotope composition of ~120 produced water samples collected from 17 producing unconventional petroleum wells in Weld County, Colorado from the Late Cretaceous Niobrara Formation. This sample set encompasses eight produced water time series from four new wells across production days 0 to ~365 and from four established wells across production days ~1000 to ~1700. Additionally, produced water from nine other established Niobrara Formation wells were sampled at discrete time points ranging from day 458 to day 2256, as well as hydraulic fracturing input fluids. These results expand the available Niobrara Formation produced water geochemical data, previously limited to a few wells sampled within the first year of production, allowing for the heterogeneity of major ions and radium to be evaluated. Specific highlights include: (i) observations that boron and bromide concentrations are higher in produced waters from new wells compared to older, established wells, suggesting the role of input fluids contributing to fluid geochemistry; and (ii) barium and radium concentrations vary between the producing benches of the Niobrara Formation with implications for treating radiological hazards in produced waters from this formation. Furthermore, we explore the geochemical relationships between major ion ratios and stable water isotope composition to understand the origin of salinity in Niobrara Formation brines from the Denver-Julesburg Basin. These findings are discussed with perspective toward potential treatment and reuse of Niobrara produced water prior to disposal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Introduction: Responsive and sensitive parenting promotes the development of self-regulation and lowers stress in children, which in turn is associated with greater educational and economic achievement and better physical and emotional health later in life. Dyadic parent-child video-feedback programs can help parents learn effective parenting skills, yet these programs are estimated to retain only about half of eligible participants. Programs vary widely, and little is known about what is valued by parents who do complete these programs. The purpose of this qualitative study was to understand the goals, experiences, and outcomes important to mothers who completed a video-feedback program., Methods: Transcripts of exit interviews of participants in a video-feedback program (N = 31) were analyzed using qualitative description methodology. Trustworthiness was achieved through deep engagement with the material, following an iterative process in analyzing transcripts, and member checks to confirm results., Results: Mothers enrolled in the program to better understand their child, help their child learn, and to develop closer connections with their child. Elements of the program that helped mothers achieve these goals were (1) positive feedback and support by the therapist, (2) dedicated one-on-one time spent with their infant, (3) help with concrete needs, and (4) learning from watching videotaped play sessions. As a result, mothers reported greater confidence as caregivers, use of more responsive and sensitive parenting strategies, and improvements in their children's behaviors and their own mental health., Discussion: Incorporating elements of the program found to be most useful in this study into video-feedback programs may make video-feedback programs more attractive to parents and increase retention. Midwives and women's health care providers may incorporate elements of the program into their clinical practice and advocacy, with special attention to elements most valued by parents themselves., (© 2022 by the American College of Nurse-Midwives.)

The aim of this study was to examine neuropsychological functioning and white matter integrity, in service members and veterans (SMVs) after mild traumatic brain injury (MTBI), with versus without post-traumatic stress disorder (PTSD). Participants were 116 U.S. military SMVs, prospectively enrolled from the Walter Reed National Military Medical Center (Bethesda, MD), who had sustained an MTBI ( n  = 86) or an injury without TBI (i.e., Injured Control [IC]; n  = 30). Participants completed a battery of neuropsychological measures (neurobehavioral and -cognitive), as well as diffusion tensor imaging (DTI) of the brain, on average 6 years post-injury. Based on diagnostic criteria for PTSD, participants in the MTBI group were classified into two subgroups: MTBI/PTSD-Present ( n  = 21) and MTBI/PTSD-Absent ( n  = 65). Participants in the IC group were included only if they were classified as PTSD-Absent. The MTBI/PTSD-Present group had a significantly higher number of self-reported symptoms on all neurobehavioral measures (e.g., depression), and lower scores on more than half of the neurocognitive domains (e.g., processing speed), compared to the MTBI/PTSD-Absent and IC/PTSD-Absent groups. There were no significant group differences for the vast majority of DTI measures, with the exception of a handful of regions (i.e., superior longitudinal fascicle and superior thalamic radiation). These results suggest that there is 1) a strong relationship between PTSD and poor neuropsychological outcome after MTBI and 2) a lack of a relationship between PTSD and white matter integrity, as measured by DTI, after MTBI. Concurrent PTSD and MTBI should be considered a risk factor for poor neuropsychological outcome that requires early intervention.

Animal data indicate that ketogenic diets are associated with improved mitochondrial function, but human data are lacking. We aimed to characterize skeletal muscle mitochondrial changes in response to a ketogenic diet combined with exercise training in healthy individuals. Twenty-nine physically active adults completed a 12-wk supervised exercise program after self-selection into a ketogenic diet (KD, n = 15) group or maintenance of their habitual mixed diet (MD, n = 14). Measures of metabolic health and muscle biopsies (vastus lateralis) were obtained before and after the intervention. Mitochondria were isolated from muscle and studied after exposure to carbohydrate (pyruvate), fat (palmitoyl-l-carnitine), and ketone (β-hydroxybutyrate+acetoacetate) substrates. Compared with MD, the KD resulted in increased whole body resting fat oxidation ( P < 0.001) and decreased fasting insulin ( P = 0.019), insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), P = 0.022], and visceral fat ( P < 0.001). The KD altered mitochondrial function as evidenced by increases in mitochondrial respiratory control ratio (19%, P = 0.009), ATP production (36%, P = 0.028), and ATP/H 2 O 2 (36%, P = 0.033) with the fat-based substrate. ATP production with the ketone-based substrate was four to eight times lower than with other substrates, indicating minimal oxidation. The KD resulted in a small decrease in muscle glycogen (14%, P = 0.035) and an increase in muscle triglyceride (81%, P = 0.006). These results expand our understanding of human adaptation to a ketogenic diet combined with exercise. In conjunction with weight loss, we observed altered skeletal muscle mitochondrial function and efficiency, an effect that may contribute to the therapeutic use of ketogenic diets in various clinical conditions, especially those associated with insulin resistance.

Background: Most patients infected with SARS-CoV-2 have mild to moderate symptoms manageable at home; however, up to 20% develop severe illness requiring additional support. Primary care practices performing population management can use these tools to remotely assess and manage COVID-19 patients and identify those needing additional medical support before becoming critically ill., Aim: We developed an innovative population management approach for managing COVID-19 patients remotely., Setting: Development, implementation, and evaluation took place in April 2020 within a large urban academic medical center primary care practice., Participants: Our panel consists of 40,000 patients. By April 27, 2020, 305 had tested positive for SARS-CoV-2 by RT-qPCR. Outreach was performed by teams of doctors, nurse practitioners, physician assistants, and nurses., Program Description: Our innovation includes an algorithm, an EMR component, and a twice daily population report for managing COVID-19 patients remotely., Program Evaluation: Of the 305 patients with COVID-19 in our practice at time of submission, 196 had returned to baseline; 54 were admitted to hospitals, six of these died, and 40 were discharged., Discussion: Our population management strategy helped us optimize at-home care for our COVID-19 patients and enabled us to identify those who require inpatient medical care in a timely fashion.

Drosophila color vision is achieved by comparing outputs from two types of color-sensitive photoreceptors, R7 and R8. Ommatidia (unit eyes) are classified into two subtypes, known as 'pale' or 'yellow', depending on Rhodopsin expression in R7 and R8. Subtype specification is controlled by a stochastic decision in R7 and instructed to the underlying R8. We find that the Activin receptor Baboon is required in R8 to receive non-redundant signaling from the three Activin ligands, activating the transcription factor dSmad2. Concomitantly, two BMP ligands activate their receptor, Thickveins, and the transcriptional effector, Mad. The Amon TGFβ processing factor appears to regulate components of the TGFβ pathway specifically in pale R7. Mad and dSmad2 cooperate to modulate the Hippo pathway kinase Warts and the growth regulator Melted; two opposing factors of a bi-stable loop regulating R8 Rhodopsin expression. Therefore, TGFβ and growth pathways interact in postmitotic cells to precisely coordinate cell-specific output.

Cells are dynamic systems capable of spontaneously switching among stable states. One striking example of this is spontaneous symmetry breaking and motility initiation in fish epithelial keratocytes. Although the biochemical and mechanical mechanisms that control steady-state migration in these cells have been well characterized, the mechanisms underlying symmetry breaking are less well understood. In this work, we have combined experimental manipulations of cell-substrate adhesion strength and myosin activity, traction force measurements, and mathematical modeling to develop a comprehensive mechanical model for symmetry breaking and motility initiation in fish epithelial keratocytes. Our results suggest that stochastic fluctuations in adhesion strength and myosin localization drive actin network flow rates in the prospective cell rear above a critical threshold. Above this threshold, high actin flow rates induce a nonlinear switch in adhesion strength, locally switching adhesions from gripping to slipping and further accelerating actin flow in the prospective cell rear, resulting in rear retraction and motility initiation. We further show, both experimentally and with model simulations, that the global levels of adhesion strength and myosin activity control the stability of the stationary state: The frequency of symmetry breaking decreases with increasing adhesion strength and increases with increasing myosin contraction. Thus, the relative strengths of two opposing mechanical forces--contractility and cell-substrate adhesion--determine the likelihood of spontaneous symmetry breaking and motility initiation.

Background: Hodgkin lymphoma (HL) is characterized by relatively few malignant Reed-Sternberg (RS) cells admixed within a reactive T cell rich inflammatory infiltrate. There is growing recognition that the HL-associated inflammatory milieu may enhance rather than inhibit growth of RS tumor cells. Since little is known of the immunophenotype of the HL inflammatory infiltrate we have performed a detailed retrospective comparison of the flow immunophenotype of HL and reactive lymphoid hyperplasia (RLH) to identify HL-specific immunophenotypic features., Methods: Single cell suspensions from 59 lymph nodes involved by HL (at initial diagnosis) and 38 lymph nodes involved by RLH were subjected to a battery of 3-color combinations of well-characterized fluorochrome-conjugated monoclonal antibodies (DAKO) to a number of lymphocyte subsets. Cells were analyzed on a FACSCalibur flow cytometer with CellQuest software (Becton Dickinson)., Results: Overall, CD4+ T cells are increased and CD19+ B cells decreased in HL vs. RLH, yielding median T:B cell (CD3:CD20) ratios of 2.3:1 and 1.6:1, resp. There is no difference in median CD8+ T cell % (16% in HL & RLH). The T:B cell ratio is highest in nodular sclerosis (NSHL) and lymphocyte depletion (LDHL) subtypes, and lowest in mixed cellularity HL (MCHL). There is no significant difference in CD4:CD8 ratio in any comparison. NKT cells were slightly increased in HL vs. RLH, especially in MCHL. CD4+CD25+ regulatory T cells are significantly increased in HL (9%) vs. RLH (2%), especially in MCHL (29%) and NSHL (12%). EBV positivity in NSHL is associated with older age, decreased CD4+CD25+ regulatory T cells, CD4:CD8 ratio, and CD19/CD20+ B cells, and increased NKT cells, and CD14+ low forward-side scatter-gated monocytes., Conclusion: The cellular composition of the reactive lymphocytic infiltrate in HL differs significantly from that seen in RLH, with significant differences also noted between HL subtypes. In general, the HL infiltrate contains increased T cells (CD4+ and NKT subsets), decreased B cells, and increased regulatory T cells in comparison with RLH. The major difference between HL subtypes is decreased CD4+ T cells in MCHL as compared with NSHL and NLPHL. The most notable EBV-related difference in NSHL is increased regulatory T cells in EBV negative cases. While many differences in the reactive lymphocytic infiltrate of Hodgkin lymphoma and reactive lymphoid hyperplasia were identified, the sole difference that may prove to be of differential diagnostic value in flow cytometric analysis of HL versus RLH is the increased percentage of CD4+ bright CD25+ regulatory T cells in HL., ((c) 2007 Clinical Cytometry Society)

We sought to determine perceptions and practices of American gynecologists when treating with a woman complaining of menorrhagia, specifically with regard to an underlying bleeding disorder as a potential cause. A mail survey of Georgia members of the American College of Obstetricians and Gynecologists was conducted. The survey response was 52%, and the analysis includes 376 physicians who reported seeing at least one gynecological patient per week. On average, respondents were in practice 20 years and reported that 8% of their patient population complain of menorrhagia. Virtually all physicians reported employing a menstrual history as a starting point for the workup for menorrhagia, and 95% order a hemoglobin/hematocrit determination. About 50% of physicians considered saturating three tampons/pads per 4 hours as excessive, although the criterion varied widely (range 0-24 per 4 hours, SD = 3). The diagnoses considered most likely among reproductive age women were anovulatory bleeding or benign lesions or that the heavy bleeding was within normal limits. Only 4% of physicians would consider von Willebrand disease (VWD) for this age group (women of reproductive age). Among girls near menarche, physicians overwhelmingly consider anovulatory bleeding or bleeding within normal limits the likely diagnoses, and 16% would consider VWD in this age group. Only rarely (3%) do surveyed physicians refer menorrhagia patients to other specialists. Most respondents believe that most menorrhagia is caused by anovulation or is within normal limits. Bleeding disorders are believed to be a rare cause of menorrhagia.

The effect of in ovo or day-of-hatch subcutaneous antibiotic administration on the detection of antibiotic residues in yolk sac or blood serum samples and the potential for observed residues to interfere with competitive exclusion (CE) culture establishment was compared in three experiments. The in ovo or subcutaneous administration of gentamicin sulfate or ceftiofur sodium was associated with detectable levels of antibiotic residues in yolk sac or blood serum samples in Experiment 1. Further, the ability to detect antibiotic residues in day-of-hatch chicks was associated with reduced levels of CE culture establishment when cecal propionate level, an indicator of PREEMPT establishment, was determined following PREEMPT application by oral gavage on the day of hatch in Experiments 1 and 2. Restricting chicks from feed, as opposed to providing access ad libitum to a starter ration, for 6 h immediately following administration of PREEMPT improved (P < 0.05) CE culture establishment in Experiment 2 in nonantibiotic injected control chicks, but did not affect (P > 0.05) experimental groups receiving either gentamicin sulfate or ceftiofur sodium by either in ovo or subcutaneous routes. The in ovo administration of 0.1 or 0.2 mg ceftiofur sodium to individual embryos on Day 18 of embryogenesis in Experiment 3 was associated with marked depressions (P < 0.05) in cecal propionate levels compared with uninjected control chicks. When feed was restricted and the time of PREEMPT administration was delayed for 48 or 72 h posthatch, mean cecal propionate levels in in ovo ceftiofur sodium-injected chicks were not significantly different (P > 0.05) from controls, indicating a time- and feed restriction-associated effect on improving CE culture establishment.

Salmonella contamination of the chicken crop has been reported to increase markedly and significantly during feed withdrawal, probably due to coprophagy, and may contribute to carcass contamination at processing. The effect of prolonged lactose administration (2.5%) in the drinking water on the incidence of Salmonella recovery from broiler crops or ceca was evaluated in seven experiments. In these experiments, all or a percentage (providing seeders and contacts) of 7-wk-old broilers were challenged with approximately 1 x 108 cfu Salmonella enteritidis and provided lactose for 5 or 11 d prior to and during an 18 or 24 h feed withdrawal period. A small but significant lactose-mediated reduction in Salmonella contamination of crops was observed in one of two identical experiments with 18 h feed withdrawal. Extending the feed withdrawal period to 24 h did not improve the ability of lactose to affect Salmonella recovery from crops or ceca. Similarly, lactose did not affect Salmonella recovery when the percentage of birds challenged was reduced to 3 out of 16 and Salmonella recovery from crops or ceca of unchallenged, contact broilers was measured. Extending the duration of exposure to 2.5% lactose in the drinking water from 5 to 11 d did not improve the ability of lactose to affect Salmonella recovery. Taken together, these data suggest that provision of 2.5% lactose in the drinking water during the last 5 to 11 d of growout prior to slaughter will not be useful in an integrated Salmonella control program under commercial conditions.

The broiler crop has recently been implicated as a major source of Salmonella contamination at commercial processing. Furthermore, feed withdrawal has been positively correlated with increased Salmonella incidence in the crop, probably due to coprophagy. In the present study, a rapid screening assay was developed to evaluate several potential disinfectants in the presence of large quantities of organic matter, simulating the crop environment. An apparent synergistic combination of d-Limonene (DL) and citric acid (CA) was observed when evaluating the potential to eliminate Salmonella in the presence of organic material. A method of encapsulation of DL and CA was developed for voluntary consumption by broilers during feed withdrawal. During an 8-h feed withdrawal individual 8-wk-old broilers voluntarily consumed an average of 21.5 capsules (total of 3.44 g material). When eight capsules were force-administered to Salmonella-challenged 8-wk-old broilers during an abbreviated 4 h feed withdrawal, Salmonella was not recovered using selective enrichment. To evaluate the effect of voluntary capsule consumption, 8-wk-old broilers were challenged with 1 x 108 cfu of Salmonella 5 d prior to an 8 h feed withdrawal. When these broilers were allowed unlimited continuous access to capsules containing DL/CA during an 8 h feed withdrawal, 24.8 capsules per broiler were ingested without affecting Salmonella recovery from crops. When access to capsules containing DL/CA was limited to the final 45 min of an 8 h feed withdrawal in a similar experiment, an average of 22.2 capsules were consumed by each broiler, resulting in a significant decrease in the number of Salmonella-positive crops. Although a number of practical questions and considerations remain, these data suggest that appropriate disinfectants could be administered during preslaughter feed withdrawal for the purpose of reducing foodborne pathogens in crops.

Despite thromboprophylaxis, deep vein thrombosis is a common complication of major orthopedic surgery. Predisposing genetic risk factors are unknown. In this case-control study, we investigated the association of the insertion (I)/deletion (D) angiotensin converting enzyme (ACE) gene polymorphism, Factor V Leiden (R506Q) mutation, and 5,10 methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with post-operative venous thrombosis in 85 patients who underwent elective total hip arthroplasty. The odds of a thrombotic event following hip surgery among subjects with the DD genotype of the ACE gene was increased more than 10-fold compared to subjects with the II genotype (odds ratio 11.7 [95% confidence interval 2.3-84.5]); it was increased 5-fold in subjects with the ID genotype compared to the II genotype (odds ratio 5.0 [95% confidence interval 1.1-34.9]). Mean plasma ACE level in control subjects not on ACE inhibitors at the time of study (n=43) was lowest in persons homozygous for the I allele (18.9+/-7.95 U/l), intermediate in patients with the ID genotype (31.6+/-10.8 U/l) and highest in subjects homozygous for the D allele (44.0+/-7.14 U/l). Mean plasma ACE level among cases was higher (33.0 U/l, n=25) than among controls (29.4 U/l, n=43) but this difference was not statistically significant. Neither the Factor V Leiden mutation nor MTHFR gene polymorphism increased the risk of thrombosis following hip replacement. These results demonstrate that the I/D ACE gene polymorphism is a potent risk factor for thrombosis in subjects undergoing total hip arthroplasty.

In recent years, several preenrichment media have been shown to be effective for use in the recovery of sublethally injured Salmonella organisms. Selective enrichment without preenrichment has resulted in a lower recovery of organisms, particularly with regard to injured or stressed salmonellae. The present experiments compared the ability of nonselective preenrichment followed by selective enrichment or direct selective enrichment alone to recover chlorine-injured Salmonella organisms. Additionally, the Salmonella detection limits of the two enrichment methods were compared with minimal infectious dose in neonatal chicks. In three experiments, Salmonella enteritidis cells were exposed to chlorine for specific times and subsequently cultured by using preenrichment followed by selective enrichment or selective enrichment alone. Simultaneously, neonatal chicks were orally challenged with S. enteritidis cells from each exposure time to chlorine. The results indicated a marginal, but significantly (P < 0.05) higher level of recovery of sublethally injured salmonellae by using nonselective preenrichment followed by selective enrichment, as compared to selective enrichment alone. Interestingly, both culture methods were capable of detecting injured S. enteritidis cells at levels incapable of infecting neonatal chicks.

Several sampling methods have been developed for the detection of Salmonella on broiler carcasses during commercial processing. The present study evaluated three sampling methodologies for sensitivity of Salmonella detection on processed broiler carcasses. Furthermore, the effect of crop removal or chill tank exposure on the frequency of Salmonella recovery was also examined. In two experiments, swab, skin, and carcass rinse samples were compared for sensitivity of Salmonella detection. The results indicated that culture of swabs was less effective (P < 0.05) for Salmonella detection than either skin or carcass rinse samples. No significant (P > 0.05) differences were observed in Salmonella recovery from culture of skin or carcass rinse. In two subsequent experiments, skin and carcass rinse samples were found to be equally sensitive in their ability to detect Salmonella. Additionally, the stages of processing between feather and crop removal were observed to cause significant (P < 0.05) increases in Salmonella recovery within an individual flock. Similar increases (P < 0.05) in Salmonella recovery were also observed following crop removal and immediately following immersion chilling in two separate flocks. These results suggest that culture of skin samples obtained from the thoracic inlet region may be a viable alternative to the traditional whole carcass rinse method for sensitivity of Salmonella detection. Furthermore, these experiments provided some evidence that the majority of Salmonella cross-contamination of carcasses prior to immersion chilling occurred following evisceration, with the chill tank potentially providing a major site for cross-contamination between Salmonella-negative and-positive flocks.

We used a hydrophobic solid support, octadecylsilylated silica gel (C18), packed in a quartz column as a reaction medium for the photolysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and 1,2,3,4-tetrachlorodibenzo-p-dioxin (1,2,3,4-TCDD). When we exposed the column to a 450 W UV lamp, the adsorbed 1,2,3,4-TCDD or 2,3,7,8-TCDD in 10% 2-propanol/water decomposed completely in 20 minutes and 5 minutes, respectively. The large estimated partition coefficient of 1,2,3,4-TCDD in 10% 2-propanol/water (> 1000) indicates that on the C18 stationary phase, both the saturated hydrocarbon chains and the absorbed 2-propanol may act as proton donors and accelerate the photolysis. In direct sunlight, the adsorbed 1,2,3,4-TCDD in 10% 2-propanol/water decomposed much faster than in a nonaqueous solvent (50% 2-propanol/methanol). This solvent effect is advantageous for the practical use of the C18 photolysis process in aqueous waste treatment. We have demonstrated that complete C18 trapping with continuous photodecomposition of TCDD contained in an aqueous alcohol waste is possible.

To purify the tetrachlorobenzo-p-dioxins synthesized for chemical and biological reference standards, reversed-phase liquid chromatography on pyrenylethyl- and octadecylsilylated stationary phase (PYE and C18) columns was employed with 100% methanol. The pyrenylethyl phase satisfactorily separated isomers resulting from mixtures of reaction products which had not been adequately separated with conventional C18 or silica gel. The use of a single chromatographic mode, liquid chromatography, and a single mobile phase with columns of distinctly different properties, C18 and PYE, separates 20 of the 22 isomers from each other and from the 1246/1249 pair. (The observed properties of the two columns afford insight into steric and polarizability differences among isomers.)

Polychlorinated dibenzofurans (PCDFs) are widespread environmental contaminants which have been detected in human tissues and implicated in several poisoning incidents. Their toxic effects are similar to those observed with other related halogenated aromatic hydrocarbons such as TCDD. The teratogenic effects of three PCDFs, 1,2,3,7,8-pentachlorodibenzofuran (1-PeCDF), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), and 1,2,3,4,7,8-hexachlorodibenzofuran (HCDF), were assessed in C57BL/6N mice. Pregnant mice were exposed on Gestation Days 10-13 to 10 ml corn oil/kg containing PCDFs. The dams were killed on Gestation Day 18 and maternal and fetal toxicity were assessed. All three compounds were highly teratogenic, with very steep and parallel dose-response curves for the two diagnostic indicators of dioxin-like teratogenicity, hydronephrosis, and cleft palate. 4-PeCDF was the most teratogenic with an ED50 of 36 micrograms/kg for cleft palate and 7 micrograms/kg for hydronephrosis. 4-PeCDF was approximately 4 times as potent as 1-PeCDF and 10 times as potent as HCDF. The teratogenic responses occurred at a dose below that where any obvious maternal or fetal toxicity was detected. Thus, these three compounds cause teratogenic responses similar to those seen with TCDD but are only 1/10 to 1/100 as potent.