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Objectives: Intrauterine device (IUD) users often encounter barriers to desired removal. Self-removal, while previously found to be successful only 19% of the time, may mitigate these obstacles. Our primary objective was to evaluate the effectiveness of our previously developed IUD self-removal guide. Our secondary objectives were to evaluate the acceptability of the guide and characterize the self-removal process. STUDY DESIGN: This was a randomized controlled trial comparing IUD self-removal success rates with and without a guide. Participants selected a clinical or nonclinical setting for self-removal. The primary outcome was the rate of successful IUD self-removal. Covariates of interest included demographic characteristics, parity, body mass index, and attempted removal setting., Results: Of the 116 participants, 35 (30%) successfully removed their IUDs, 20 (32%) randomized to the guide, and 15 (28%) randomized to no guide (p = 0.7). While our guide was not associated with increased successful self-removal, the majority (97%) of those randomized to it reported it to be helpful. Those who selected a nonclinical setting (80%) were more successful at self-removal (35% vs 9%, p = 0.01). Most participants would recommend IUD self-removal to a friend (68%) and attempt again with a future IUD (80%)., Conclusions: The proportion of participants who successfully removed their IUDs was higher than previously shown, with or without the use of our guide. Our inclusion of a nonclinical setting was novel, in which the proportion of successful self-removal was significantly higher. Providers should consider discussion of IUD self-removal, with a reasonable expectation about the likelihood of success, as a means of increasing reproductive autonomy., Implications: IUD self-removal was feasible and acceptable., (Published by Elsevier Inc.)

Hypothesis/background: Patient-specific implants have become an increasingly researched area to improve surgical outcomes. Patient-specific implants have been suggested to provide advantages for better implant alignment and thus improve surgical outcomes. One such area for application is in the use of intramedullary nails for humeral fracture stabilization. However, the anatomy of the canal is not well defined, especially in a larger scale demographic study., Methods: In this observational cross-sectional study, axial computed tomography scans of 150 humeri were used to measure the cortical thickness and canal width in both coronal and sagittal orientations. Measurements were made at 7 evenly spaced levels along the humerus from the surgical neck to the point immediately superior to the supracondylar ridge. X-rays were used to measure the valgus, recurvatum, and procurvatum angles, along with their associated locations. Demographic data recorded included age, gender, body mass index (BMI), race, and ethnicity., Results: The mean coronal canal widths decreased inferiorly from the surgical neck to midshaft before increasing to the supracondylar fossa. Mean sagittal widths decreased along the complete course of the canal. The ratio of coronal to sagittal canal widths decreased from 1.09 at level 1 to 0.83 at level 5 before increasing to 1.30 at level 7. Females had significantly smaller canal widths and cortex thicknesses in both the sagittal and coronal planes throughout the course of the canal. There were no significant differences in canal widths among ethnicities. Age was positively correlated with the canal width in the coronal and sagittal orientations but was negatively correlated with cortical thickness in all 7 levels. BMI was not significantly correlated with canal width., Conclusion/discussion: The data included in this study may be used to determine standard widths and measurements of the humerus. However, there are notable patterns or differences in the shape of the medullary canal of the humerus between subgroups. This study is the first to conduct a larger scale demographic investigation comparing the humeral canal characteristics among sex, ethnicity, age, and BMI. These data may serve as a platform to further investigate the course of the medullary canal., (© 2024 The Author(s).)

Hypothesis: We sought to determine whether patients' preoperative resilience scores predict postoperative outcomes in arthroscopic rotator cuff repair surgery., Methods: Patients were prospectively enrolled and underwent data collection preoperatively and at 3, 6, 12, and 24 months postoperatively. Data collected included demographic characteristics and the Brief Resilience Scale (BRS) score, visual analog scale score, Veterans RAND 12-Item Health Survey scores (mental component [VR-12M] and physical component [VR-12P]), American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form score, Single Assessment Numeric Evaluation score, and Simple Shoulder Test (SST) score., Results: In total, 131 patients had complete 1- or 2-year postoperative outcome measures. Female patients comprised 56.5% of our sample, and the average age was 57.6 years. Between the low, normal, and high resilience groups, there were significant differences in the VR-12M scores at 0, 12, and 24 months postoperatively (P < .01 for all). The VR-12P scores at 12 months were 44.2, 47.4, and 49.8 in the low, normal, and high resilience groups, respectively, showing a trend upward, but this failed to reach the level of significance (P = .08). The SST scores of the low, normal, and high resilience groups at 12 months were 69.1, 79.9, and 85.1, respectively, again showing a trend upward, but this failed to reach the level of significance (P = .07). The SST scores at 0 and 24 months did not differ between groups. There were no significant differences in American Shoulder and Elbow Surgeons, visual analog scale, and Single Assessment Numeric Evaluation scores at 0, 12, or 24 months postoperatively. We found a significant positive correlation between the BRS score and SST score at 12 months (R = 0.18), VR-12M score at 12 months (R = 0.38), VR-12M score at 24 months (R = 0.31), and VR-12P score at 12 months (R = 0.21)., Conclusions: Our study provides evidence that BRS scores in patients undergoing arthroscopic rotator cuff repair are related to postoperative outcomes, measured through the VR-12M and SST scores at 2-year follow-up., (Copyright © 2023 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Biomedical sciences PhDs pursue a wide range of careers inside and outside academia. However, there is little data regarding how career interests of PhD students relate to the decision to pursue postdoctoral training or to their eventual career outcomes. Here, we present the career goals and career outcomes of 1452 biomedical sciences PhDs who graduated from Vanderbilt University between 1997 and 2021. We categorized careers using an expanded three-tiered taxonomy and flags that delineate key career milestones. We also analyzed career goal changes between matriculation and doctoral defense, and the reasons why students became more- or less-interested in research-intensive faculty careers. We linked students' career goal at doctoral defense to whether they did a postdoc, the duration of time between doctoral defense and the first non-training position, the career area of the first non-training position, and the career area of the job at 10 years after graduation. Finally, we followed individual careers for 10 years after graduation to characterize movement between different career areas over time. We found that most students changed their career goal during graduate school, declining numbers of alumni pursued postdoctoral training, many alumni entered first non-training positions in a different career area than their goal at doctoral defense, and the career area of the first non-training position was a good indicator of the job that alumni held 10 years after graduation. Our findings emphasize that students need a wide range of career development opportunities and career mentoring during graduate school to prepare them for futures in research and research-related professions., Competing Interests: The authors declare no conflicts of interest., (©2023 The Authors FASEB BioAdvances published by The Federation of American Societies for Experimental Biology.)

College athletes may be vulnerable to sleep disturbances and depression during the COVID-19 pandemic as a result of large shifts in social and athletic obligations. In a national sample of college athletes, we examined the associations between sleep disturbances and depression across two timepoints, using COVID-19 exposure as a moderator. Data were collected from 2098 NCAA Division I, II, and III college athletes during two timepoints, from April 10 to May 23, and from August 4 to September 15, 2020. First, a latent class analysis was conducted with five indicators of levels of COVID-19 exposure to determine different exposure profiles. Second, to examine the directionality of associations between sleep disturbance and depression, a cross-lagged panel model was added to the latent class membership structural equation model; this allowed for testing of moderation by COVID exposure class membership. Four highly homogeneous, well-separated classes of COVID-19 exposure were enumerated: Low Exposure (57%); Quarantine Only (21%); High Other, Low Self Exposure (14%); and High Exposure (8%). COVID-19 exposure class membership did not significantly moderate associations between sleep disturbances and depression. However, student athletes significantly differed in T2 depression by their COVID-19 exposure class membership. Depression and sleep disturbances were positively correlated at both timepoints ( r T1  = 0.39; r T2  = 0.30). Additionally, cross-lagged associations were found such that T2 depression was associated with T1 sleep disturbances ( β  = 0.14) and vice versa ( β  = 0.11). These cross-lagged associations were not significantly affected by athletes' level of COVID-19 exposure during the beginning of the pandemic., Competing Interests: We, the authors, have no financial interests or benefits in this research to disclose., (© 2023 Elsevier Ltd. All rights reserved.)

Background: The intrauterine device (IUD) is a highly effective form of long-acting reversible contraception (LARC) with few contraindications. Users, however, often encounter barriers to desired removal. IUD self-removal may mitigate these obstacles. We sought to develop a guide for IUD self-removal with the aim of increasing user control over the method., Methods: This was a two-phase mixed-methods qualitative and small pilot study with the aim of developing an IUD self-removal guide. We conducted an online content analysis of advice for IUD self-removal as well as interviews with expert key informants to develop an IUD self-removal guide. We next recruited IUD-users who had previously attempted self-removal to participate in focus group discussion and individual interviews to further refine the guide. In the second phase of the study, we piloted the guide among eight IUD-users seeking removal interested in attempting self-removal., Results: Expert key informants agreed that IUD self-removal was safe and low risk. The primary components of successful IUD self-removal elicited were ability to feel and grasp the strings, a crouched down position, and multiple attempts. A preference for presenting IUD self-removal as safe was emphasized. In the second phase, participants in the clinical pilot suggested more information for non-palpable strings, but liked the style and information provided. One participant successfully removed their IUD., Conclusions: IUD-users reported satisfaction with our guide. In our small pilot, the majority were unable to remove their own IUD. A larger study is needed to assess acceptability, feasibility, and efficacy in increasing successful self-removal., (© 2022. The Author(s).)

Background: A significant portion of the adults suffer from foot and ankle pain. The sex differences that exist throughout health care, pain management, and orthopedics may further complicate treatment strategies. The purpose of this study was to determine if there were any differences in women and men in health care seeking behavior and symptom chronicity in a West Texas orthopedic population with foot and ankle conditions., Materials and Methods: Data from 137 patients were collected in a retrospective chart review. Data were analyzed to determine if there were sex differences in time to primary care provider (PCP) after ankle injury, referral time from PCP to orthopedic surgeon consult, time from orthopedic consult to surgical intervention (if applicable), and chronicity of symptoms., Results: Women had a significantly higher percentage of chronic injuries than men (30.7% vs. 10.9%), but there were no sex differences in time to PCP from the time of injury, time from PCP visit to orthopedic consult, and time from orthopedic consult to surgical intervention. There were also no differences in those same time frames when compared by chronicity of symptoms (acute injury vs. chronic injury). Finally, we did not find any differences in pain scores between sexes or chronicity of symptoms., Conclusions: This study suggests that conventional health seeking sex differences may not apply to the foot and ankle patient population in West Texas and surrounding rural areas. Continuing to examine patterns in sex differences may lead to the development of more efficient and tailored treatment approaches and better outcomes., Competing Interests: No competing financial interests exist., (© Kyla A. Petrie et al., 2022; Published by Mary Ann Liebert, Inc.)

PhD-trained scientists are essential contributors to the workforce in diverse employment sectors that include academia, industry, government, and nonprofit organizations. Hence, best practices for training the future biomedical workforce are of national concern. Complementing coursework and laboratory research training, many institutions now offer professional training that enables career exploration and develops a broad set of skills critical to various career paths. The National Institutes of Health (NIH) funded academic institutions to design innovative programming to enable this professional development through a mechanism known as Broadening Experiences in Scientific Training (BEST). Programming at the NIH BEST awardee institutions included career panels, skill-building workshops, job search workshops, site visits, and internships. Because doctoral training is lengthy and requires focused attention on dissertation research, an initial concern was that students participating in additional complementary training activities might exhibit an increased time to degree or diminished research productivity. Metrics were analyzed from 10 NIH BEST awardee institutions to address this concern, using time to degree and publication records as measures of efficiency and productivity. Comparing doctoral students who participated to those who did not, results revealed that across these diverse academic institutions, there were no differences in time to degree or manuscript output. Our findings support the policy that doctoral students should participate in career and professional development opportunities that are intended to prepare them for a variety of diverse and important careers in the workforce., Competing Interests: The authors have declared that no competing interests exist.

In the United States, the credentialing of PhD-scientists as medical directors of clinical laboratories is driven by formal postdoctoral training programs. Prior to acceptance in one these accredited fellowships, however, a trainee's exposure to the field can be far less standardized, with significant ramifications for their awareness and competitiveness. In the current article, we describe our recent experiences in developing local, institution-based immersion opportunities for PhD experiences in the subdisciplines of laboratory medicine (clinical microbiology, clinical chemistry, and molecular genetics/genomics). It is our hope that this article-and a corresponding online survey-can prompt reflection and discussion on the status of early career training opportunities in these key clinical areas., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: There has been a groundswell of national support for transparent tracking and dissemination of PhD career outcomes. In 2017, individuals from multiple institutions and professional organizations met to create the Unified Career Outcomes Taxonomy (UCOT 2017), a three-tiered taxonomy to help institutions uniformly classify career outcomes of PhD graduates. Early adopters of UCOT 2017, noted ambiguity in some categories of the career taxonomy, raising questions about its consistent application within and across institutions. Methods: To test and evaluate the consistency of UCOT 2017, we calculated inter-rater reliability across two rounds of iterative refinement of the career taxonomy, classifying over 800 PhD alumni records via nine coders. Results: We identified areas of discordance in the taxonomy, and progressively refined UCOT 2017 and an accompanying Guidance Document to improve inter-rater reliability across all three tiers of the career taxonomy. However, differing interpretations of the classifications, especially for faculty classifications in the third tier, resulted in continued discordance among the coders. We addressed this discordance with clarifying language in the Guidance Document, and proposed the addition of a flag system for identification of the title, rank, and prefix of faculty members. This labeling system provides the additional benefit of highlighting the granularity and the intersectionality of faculty job functions, while maintaining the ability to sort by - and report data on - faculty and postdoctoral trainee roles, as is required by some national and federal reporting guidelines. We provide specific crosswalk guidance for how a user may choose to incorporate our suggestions while maintaining the ability to report in accordance with UCOT 2017. Conclusions: Our findings underscore the importance of detailed guidance documents, coder training, and periodic collaborative review of career outcomes taxonomies as PhD careers evolve in the global workforce. Implications for coder-training and use of novice coders are also discussed., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Stayart CA et al.)

Many biomedical PhD trainees lack exposure to business principles, which limits their competitiveness and effectiveness in academic and industry careers. To fill this training gap, we developed Business and Management Principles for Scientists, a semester-long program that combined didactic exposure to business fundamentals with practical team-based projects aimed at solving real business problems encountered by institutional shared--resource core facilities. The program also included a retreat featuring presentations by and networking with local life science entrepreneurs and final team presentations to expert judges. Quantitative and qualitative metrics were used to evaluate the program's impact on trainees. A pretest-posttest approach was used to assess trainees' baseline knowledge and mastery of module concepts, and each individual's pretest and posttest responses were compared. The mean score improved by more than 17 percentage points. Trainees also took an online survey to provide feedback about the module. Nearly all participants agreed or strongly agreed that the module was a valuable use of their time and will help guide their career decisions and that project work helped drive home module concepts. More than 75% of trainees reported discussing the module with their research advisors, and all of these participants reported supportive or neutral responses. Collectively, the trainee feedback about the module, improvement in test scores, and trainee perception of advisor support suggest that this short module is an effective method of providing scientists with efficient and meaningful exposure to business concepts., (© 2017 K. A. Petrie et al. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)

Historically, admissions committees for biomedical Ph.D. programs have heavily weighed GRE scores when considering applications for admission. The predictive validity of GRE scores on graduate student success is unclear, and there have been no recent investigations specifically on the relationship between general GRE scores and graduate student success in biomedical research. Data from Vanderbilt University Medical School's biomedical umbrella program were used to test to what extent GRE scores can predict outcomes in graduate school training when controlling for other admissions information. Overall, the GRE did not prove useful in predicating who will graduate with a Ph.D., pass the qualifying exam, have a shorter time to defense, deliver more conference presentations, publish more first author papers, or obtain an individual grant or fellowship. GRE scores were found to be moderate predictors of first semester grades, and weak to moderate predictors of graduate GPA and some elements of a faculty evaluation. These findings suggest admissions committees of biomedical doctoral programs should consider minimizing their reliance on GRE scores to predict the important measures of progress in the program and student productivity., Competing Interests: The authors have declared that no competing interests exist.

Background: Validity of oral contraceptive pill (OCP) clinical trial results depends on participant compliance. Ethinyl estradiol (EE2) induces increases in hepatic binding globulin (BG) levels. Measuring these BG increases may provide an effective and convenient approach to distinguish noncompliant from compliant OCP users in research settings. This analysis evaluated the usefulness of measuring increases in corticosteroid-, sex-hormone- and thyroxine-binding globulins (CBG, SHBG and TBG, respectively) as measures of OCP compliance., Methods: We used frozen serum from a trial that compared ovarian suppression between normal-weight and obese women randomized to one of two OCPs containing EE2 and levonorgestrel (LNG). Based on serial LNG measurements during the trial, 17% of participants were noncompliant. We matched noncompliant participants with compliant participants by age, body mass index, ethnicity and OCP formulation. We measured CBG, SHBG and TBG levels and compared change from baseline to 3-month follow-up between the noncompliant and compliant participants. Construction of receiver operator characteristic (ROC) curves allowed comparison of various BG measures., Results: Changes in CBG and TBG distinguished OCP noncompliant users from compliant users [area under the ROC curve (AUROC), 0.86 and 0.89, p<.01]. Changes in SHBG were less discriminating (AUROC 0.69), Conclusions: EE2-induced increases in CBG and TBG provide a sensitive integrated marker of compliance with an LNG-containing OCP., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: This study was conducted to compare ovarian suppression during oral vs. vaginal hormonal contraceptive use. Secondary aims included comparison of endometrial thickness and bleeding patterns., Methods: In two open-label trials assessing ovarian suppression, 33 compliant women completed both studies. They first used oral contraceptive pills (OCs) [randomized to either 20 mcg ethinyl estradiol (EE)/100 mcg levonorgestrel (LNG) or 30 mcg EE/150 mcg LNG] and subsequently used contraceptive vaginal rings (CVRs) (daily release of 15 mcg EE/120 mcg etonogestrel), all 21/7-day regimens. Participants had at least one run-in cycle using each contraceptive method prior to evaluation. During one cycle of each method, women underwent biweekly transvaginal sonography to measure ovarian follicular diameters and endometrial thickness. We also noted presence of a corpus luteum or a ruptured follicle as a marker of ovulation. Participants recorded bleeding days on paper calendars. We used matched-pairs analyses as appropriate., Results: During follow-up, we identified at least one ovarian follicle ≥8 mm in 20/33 (61%) OC users and 12/33 (36%) CVR users (matched-pairs analysis, p=.02). Similar trends were seen for larger follicles; however, we had limited statistical power to evaluate these differences. Median follicular diameter among OC users was larger than median follicular diameter among CVR users (p=.01). We did not observe a corpus luteum or ruptured follicle in any participant during either study. Endometrial thickness was similar during OC and CVR use (mean 4.1±1.4 vs. 4.1±1.6 mm, p=.9), as was the number of bleeding or spotting days (mean 2.1±2.4 vs. 1.9±2.1, p=.8). Oral contraceptive pill dose was unrelated to follicle diameter, endometrial thickness or bleeding., Conclusions: Ovarian follicles ≥8 mm were more common in 33 compliant women during OC use than during CVR use, indicating that CVR use results in greater ovarian suppression than OC use., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, autosomal dominant condition, classically characterised by heterotopic ossification beginning in childhood and congenital great toe malformations; occurring in response to a c.617 G > A ACVR1 mutation in the functionally important glycine/serine-rich domain of exon 6. Here we describe a novel c.587 T > C mutation in the glycine/serine-rich domain of ACVR1, associated with delayed onset of heterotopic ossification and an exceptionally mild clinical course. Absence of great toe malformations, the presence of early ossification of the cervical spine facets joints, plus mild bilateral camptodactyly of the 5th fingers, together with a novel ACVR1 mutation, are consistent with the 'FOP-variant' syndrome. The c.587 T > C mutation replaces a conserved leucine with proline at residue 196. Modelling of the mutant protein reveals a steric clash with the kinase domain that will weaken interactions with FKBP12 and induce exposure of the glycine/serine-rich repeat. The mutant receptor is predicted to be hypersensitive to ligand stimulation rather than being constitutively active, consistent with the mild clinical phenotype. This case extends our understanding of the 'FOP-variant' syndrome., (Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.)

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, heritable condition typified by progression of extensive ossification within skeletal muscle, ligament and tendon together with defects in skeletal development. The condition is easily diagnosed by the presence of shortened great toes and there is severe advancement of disability with age. FOP has been shown to result from a point mutation (c.617G>A) in the ACVR1 gene in almost all patients reported. Very recently two other mutations have been described in three FOP patients. We present here evidence for two further unique mutations (c.605G>T and c.983G>A) in this gene in two FOP patients with some atypical digit abnormalities and other clinical features. The observation of disparate missense mutations mapped to the GS and kinase domains of the protein supports the disease model of mild kinase activation and provides a potential rationale for phenotypic variation.

Converging data suggest a dysfunction of prefrontal cortical GABAergic interneurons in schizophrenia. Morphological and physiological studies indicate that cortical GABA cells are modulated by a variety of afferents. The peptide transmitter neurotensin may be one such modulator of interneurons. In the rat prefrontal cortex (PFC), neurotensin is exclusively localized to dopamine axons and has been suggested to be decreased in schizophrenia. However, the effects of neurotensin on cortical interneurons are poorly understood. We used in vivo microdialysis in freely moving rats to assess whether neurotensin regulates PFC GABAergic interneurons. Intra-PFC administration of neurotensin concentration-dependently increased extracellular GABA levels; this effect was impulse dependent, being blocked by treatment with tetrodotoxin. The ability of neurotensin to increase GABA levels in the PFC was also blocked by pretreatment with 2-[1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazole-3-yl)carbonylamino]tricyclo(3.3.1.1 [EC] .3.7)decan-2-carboxylic acid (SR48692), a high-affinity neurotensin receptor 1 (NTR1) antagonist. This finding is consistent with our observation that NTR1 was localized to GABAergic interneurons in the PFC, particularly parvalbumin-containing interneurons. Because neurotensin is exclusively localized to dopamine axons in the PFC, we also determined whether neurotensin plays a role in the ability of dopamine agonists to increase extracellular GABA levels. We found that D2 agonist-elicited increases in PFC GABA levels were blocked by pretreatment with SR48692, consistent with data indicating that D2 autoreceptor agonists increase neurotensin release from dopamine-neurotensin axons in the PFC. These findings suggest that neurotensin plays an important role in regulating prefrontal cortical interneurons and that it may be useful to consider neurotensin agonists as an adjunct in the treatment of schizophrenia.

Dopaminergic axons innervating the prefrontal cortex (PFC) target both pyramidal cells and GABAergic interneurons. Many of these dopamine (DA) axons in the rat coexpress the peptide neurotransmitter neurotensin. Previous electrophysiological data have suggested that neurotensin activates GABAergic interneurons in the PFC. Activation of D2-like DA receptors increases extracellular GABA levels in the PFC, as opposed to the striatum, where D2 receptor activation inhibits GABAergic neurons. Because activation of presynaptic D2 release-modulating autoreceptors in the PFC suppresses DA release but increases release of the cotransmitter neurotensin, D2 agonists may enhance the activity of GABAergic interneurons via release of neurotensin. In order to determine if neurotensin can activate GABAergic interneurons, we treated rats with the peptide neurotensin agonist, PD149163, and examined Fos expression in PFC neurons. Systemic administration of PD149163 increased overall Fos expression in the PFC, but not in the dorsal striatum. PD149163 induced Fos in PFC interneurons, as defined by the presence of calcium-binding proteins, and in pyramidal cells. Pretreatment with the high-affinity neurotensin antagonist, SR48692, blocked neurotensin agonist-induced Fos expression. These data suggest that neurotensin activates interneurons in the PFC of the rat.

This article reviews the basic principles of pharmacology and teratogenicity of drugs for the pregnant and lactating woman and summarizes the Food and Drug Administration, American College of Obstetrics and Gynecology, and American Academy of Pediatrics classifications. These categories were devised for caregivers of both women and their babies. The authors propose a two/three letter category system to assist those who, like family physicians, must care for women while pregnant and while lactating. Common problems from everyday practice are reviewed, with an emphasis on the important drugs to use and avoid in a wide variety of everyday clinical settings to help the busy primary care physician in making decisions about medications in pregnancy and lactation.

Primary care physicians are confronted daily with questions from their patients about alternative medicine. When maternity care patients seek information about such therapies, careful attention must be paid to issues of safety and efficacy for both the mother and her unborn child. This article clarifies the role of alternative medicine in maternity care by looking at the definitions and history of common alternative therapies, documenting the evidence for alternative therapies in prenatal, intrapartum, and postpartum care, and suggesting ways to incorporate alternative medicine into primary care practice.

Background and Purpose: Glutamate, a major excitatory neurotransmitter in the brain, has been implicated in the hyperemic response to increases in the activity of neurons, but the mechanism of glutamate-induced dilation of cerebral blood vessels is unknown. Glutamate has been shown to enhance the release of arachidonic acid (AA) in brain tissue and cultured astrocytes. We have previously shown that astrocytes metabolize AA to vasodilator products, epoxyeicostrienoic acids (EETs), and express a P-450 AA epoxygenase, P-450 2C11. We tested the hypothesis that glutamate-induced dilation of cerebral arterioles is mediated in part by changes in the formation and release of EETs by perivascular astrocytes., Methods: Primary astrocyte cultures were prepared from 3-day-old rat pups. The cells were labeled with [14C]AA, and the effect of glutamate on the formation of EETs from [14C]AA by cultured astrocytes was studied. The expression of P-450 2C11 protein in the microsomal fractions of cultured astrocytes was assessed by Western blot. In vivo cerebral blood flow measurements were made in adult rats by laser-Doppler flowmetry after administration of glutamate into the subdural space of the rat before and after treatment with miconazole., Results: Glutamate treatment (100 mumol/L for 30 minutes) induced a threefold increase in the formation of EETs from [14C]AA by cultured astrocytes, and the increase was inhibited by miconazole (20 mumol/L), an inhibitor of P-450 AA epoxygenase. Treatment with glutamate (100 mumol/L) for 12 hours increased the expression of P-450 2C11 protein in the microsomal fraction of cultured astrocytes. The response of laser-Doppler cerebral blood flow to administration of glutamate (500 mumol/L) into the subdural space of the rat was significantly attenuated after treatment with miconazole (20 mumol/L for 30 minutes)., Conclusions: These findings suggest a role for a P-450 AA epoxygenase in astrocytes in the coupling between the metabolic activity of neurons and regional blood flow in the brain.

We sought to investigate effects of lipoprotein lipase (LpL) on cellular catabolism of lipoproteins rich in apolipoprotein B-100. LpL increased cellular degradation of lipoprotein(a) (Lp(a)) and low density lipoprotein (LDL) by 277% +/- 3.8% and 32.5% +/- 4.1%, respectively, and cell association by 509% +/- 8.7% and 83.9% +/- 4.0%. The enhanced degradation was entirely lysosomal. Enhanced degradation of Lp(a) had at least two components, one LDL receptor-dependent and unaffected by heparitinase digestion of the cells, and the other LDL receptor-independent and heparitinase-sensitive. The effect of LpL on LDL degradation was entirely LDL receptor-independent, heparitinase-sensitive, and essentially absent from mutant Chinese hamster ovary cells that lack cell surface heparan sulfate proteoglycans. Enhanced cell association of Lp(a) and LDL was largely LDL receptor-independent and heparitinase-sensitive. The ability of LpL to reduce net secretion of apolipoprotein B-100 by HepG2 cells by enhancing cellular reuptake of nascent lipoproteins was also LDL receptor-independent and heparitinase-sensitive. None of these effects on Lp(a), LDL, or nascent lipoproteins required LpL enzymatic activity. We conclude that LpL promotes binding of apolipoprotein B-100-rich lipoproteins to cell surface heparan sulfate proteoglycans. LpL also enhanced the otherwise weak binding of Lp(a) to LDL receptors. The heparan sulfate proteoglycan pathway represents a novel catabolic mechanism that may allow substantial cellular and interstitial accumulation of cholesteryl ester-rich lipoproteins, independent of feedback inhibition by cellular sterol content.

We showed previously that net secretory output of apolipoprotein B (apo B) from cultured human hepatoma cells (HepG2) is regulated by rapid reuptake of nascent lipoproteins before they have diffused away from the vicinity of the cells. We now sought to determine if the nascent lipoproteins could be remodeled to enhance or impede reuptake. We found that lipoprotein lipase (LpL), an enzyme that hydrolyzes lipoprotein triglyceride, reduced HepG2 output of apo B to one-quarter to one-half of control. The reduction was apparent during co-incubations as short as 2 h and as long as 24 h. Heparin, which blocks receptor-mediated binding of lipoproteins, abolished the effect of LpL on apo B output, without causing enzyme inhibition. To assess uptake directly, we prepared labeled nascent lipoproteins. LpL tripled the cellular uptake of labeled nascent lipoproteins, from 15.2% +/- 0.7% to 48.7% +/- 0.3% of the total applied to the cells. Cellular uptake of 125I-labeled anti-LDL receptor IgG was unaffected by LpL; thus, LpL enhanced reuptake by altering lipoproteins, not receptors. Because LpL is present in the space of Disse in the liver, we conclude that LpL may act on newly secreted lipoproteins to enhance reuptake in vivo. LpL deficiency would reduce local reuptake of apo B, which would appear as overproduction, thereby providing a mechanistic link between partial LpL deficiency and familial combined hyperlipidemia.