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Objectives: The ideal assessment after mifepristone and misoprostol for undesired pregnancy of unknown location (PUL) is unknown., Study Design: We prospectively followed patients at Planned Parenthood League of Massachusetts (2019-2021) with PUL who received immediate mifepristone and misoprostol with serial at-home urine pregnancy tests (UPT) and in-office serum HCGs., Results: Of 13 patients, 10 had a successful medication abortion. For those who completed UPTs (N = 9), all were negative by Day 14. Two abnormal pregnancies had positive UPTs on Day 14., Conclusion: A negative UPT on Day 14 may help determine complete abortion after medication abortion for undesired PUL. A positive UPT on Day 14 warrants further evaluation., Implication: Patients taking mifepristone and misoprostol in the setting of undesired PUL who cannot access serum testing may consider an at-home UPT to confirm complete abortion., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Abortion is a common medical procedure in the United States that is frequently the target of political and legal restrictions. These restrictions can negatively impact care and interfere with the patient-provider relationship. In this paper, we aim to review the historic context in which feticidal agents became more utilized in later abortion; describe current practices and protocols of using feticidal agents use for later abortion by dilation and evacuation and induction of labor; evaluate patient and provider perspectives on feticidal agent use; and propose areas of further ethical and research inquiry to characterize the use of these agents in later abortion procedures., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Placentas of obese women have low mitochondrial β-oxidation of fatty acids (FA) and accumulate lipids in late pregnancy. This creates a lipotoxic environment, impairing placental efficiency. We hypothesized that placental FA metabolism is impaired in women with obesity from early pregnancy. We assessed expression of key regulators of FA metabolism in first trimester placentas of lean and obese women. Maternal fasting triglyceride and insulin levels were measured in plasma collected at the time of procedure. Expression of genes associated with FA oxidation (FAO; ACOX1, CPT2, AMPKα), FA uptake (LPL, LIPG, MFSD2A), FA synthesis (ACACA) and storage (PLIN2) were significantly reduced in placentas of obese compared to lean women. This effect was exacerbated in placentas of male fetuses. Placental ACOX1 protein was higher in women with obesity and correlated with maternal circulating triglycerides. The PPARα pathway was enriched for placental genes impacted by obesity, and PPARα antagonism significantly reduced 3 H-palmitate oxidation in 1 st trimester placental explants. These results demonstrate that obesity and hyperlipidemia impact placental FA metabolism as early as 7 weeks of pregnancy., (© 2022. The Author(s).)

Competing Interests: Financial Disclosure Alisa Beth Goldberg disclosed that money was paid to her institution from Merck and to her directly from UpToDate. Isabel Fulcher received payment as a statistical consultant at Planned Parenthood League of Massachusetts. Jennifer Fortin is employed by Planned Parenthood League of Massachusetts. Rebecca Hofer disclosed that she was employed as a research assistant during the time of the study. She received an hourly wage from Planned Parenthood, including for work related to the study discussed as well as for other studies. She is no longer employed there and received no compensation for reviewing and contributing to the manuscript. In addition, she owns a number of different independent stocks and mutual funds that she has had for many years prior to the current work. These were purchased by her and her family and are not related to the current research. Alex Cottrill disclosed that the original study the Letter to the Editor addresses was funded by a grant paid to the authors' institution from the Society for Family Planning Research Fund. Dr. Cottrill was employed full-time by Planned Parenthood League of Massachusetts (where this study was based) during the 36 months before the original submission. Dr. Cottrill's salary was partly funded by our SFPRF grant during that time. Dr. Cottrill is still on the payroll at PPLM per diem but has not been paid through that grant since. Daniele Roncari received payment from Organon as a trainer for Nexplanon. The other authors did not report any potential conflicts of interest.

Objective: To compare immediate initiation with delayed initiation of medication abortion among patients with an undesired pregnancy of unknown location., Methods: This retrospective cohort study used electronic medical record data from the Planned Parenthood League of Massachusetts (2014-2019) for patients who requested medication abortion with a last menstrual period (LMP) of 42 days or less and pregnancy of unknown location (no gestational sac) on initial ultrasonogram. Clinicians could initiate medication abortion with mifepristone followed by misoprostol while simultaneously excluding ectopic pregnancy with serial serum human chorionic gonadotropin (hCG) testing (same-day-start group) or establish a diagnosis with serial hCG tests and repeat ultrasonogram before initiating treatment (delay-for-diagnosis group). We compared primary safety outcomes (time to diagnosis of pregnancy location [rule out ectopic], emergency department visits, adverse events, and nonadherence with follow-up) between groups. We also reported secondary efficacy outcomes: time to complete abortion, successful medication abortion (no uterine aspiration), and ongoing pregnancy., Results: Of 5,619 medication abortion visits for patients with an LMP of 42 days or less, 452 patients had pregnancy of unknown location (8.0%). Three patients underwent immediate uterine aspiration, 55 had same-day start, and 394 had delay for diagnosis. Thirty-one patients (7.9%), all in the delay-for-diagnosis group, were treated for ectopic pregnancy, including four that were ruptured. Among patients with no major ectopic pregnancy risk factors (n=432), same-day start had shorter time to diagnosis (median 5.0 days vs 9.0 days; P=.005), with no significant difference in emergency department visits (adjusted odds ratio [aOR] 0.90, 95% CI 0.43-1.88) or nonadherence with follow-up (aOR 0.92, 95% CI 0.39-2.15). Among patients who proceeded with abortion (n=270), same-day start had shorter time to complete abortion (median 5.0 days vs 19.0 days; P<.001). Of those who had medication abortion with known outcome (n=170), the rate of successful medication abortion was lower (85.4% vs 96.7%; P=.013) and the rate of ongoing pregnancy was higher (10.4% vs 2.5%; P=.041) among patients in the same-day-start group., Conclusion: In patients with undesired pregnancy of unknown location, immediate initiation of medication abortion is associated with more rapid exclusion of ectopic pregnancy and pregnancy termination but lower abortion efficacy., Competing Interests: Financial Disclosure Alisa B. Goldberg was supported by the Society of Family Planning Research Fund [SFPRF12-MA7], which was awarded to the Planned Parenthood League of Massachusetts. She received royalties from UpToDate and was a consultant for Sanofi/Genzyme from 2018 to 2019. Danielle Roncari reports receiving payment from Organon as a Nexplanon trainer. The following authors are or were employed by Planned Parenthood League of Massachusetts during the study: Jennifer Fortin, Rebecca Hofer, and Alex Cottrill. The other authors did not report any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To determine if obese women experience increased rates of adverse outcomes with moderate intravenous sedation during first trimester surgical abortion compared to normal weight women., Study Design: We performed a retrospective cohort study of all first trimester surgical abortions with moderate intravenous sedation at an outpatient facility between September 2010 and June 2015. The primary outcome was supplemental oxygen administration. Secondary outcomes included reversal agent administration, anesthesia-related adverse events, and intraoperative lowest level of consciousness (LLOC). We compared three obesity groups [I (Body Mass Index, BMI=30-34.9), II (BMI=35-39.9), and III (BMI ≥40)] to normal weight women (BMI <25). We exported data from electronic medical records and reviewed adverse outcomes individually., Results: Of 20,381 first trimester surgical abortion procedures, 31 (0.15%) utilized supplemental oxygen, 24 (0.12%) utilized a reversal agent, 40 (0.20%) had a presumed anesthesia-related adverse event and 184 of 19,725 (0.93%) had a documented low intraoperative LLOC. One patient (0.005%) required hospital transfer or hospitalization. Supplemental oxygen administration (obesity versus normal weight: obese I, aOR 0.52, 95% CI 0.12-2.27; II/III, aOR 1.51, 95% CI 0.50-4.54), low intraoperative LLOC, and anesthesia-related adverse events were not associated with obesity. The rate of reversal agent administration was lower among obese I, II and III women combined compared to normal weight women (aOR 0.13, 95% CI 0.02-0.96)., Conclusions: Adverse outcomes were rare across all BMI categories with no detectable increased risk among obese women compared to normal weight women., Implications: With appropriate clinical screening, obese women can safely receive moderate intravenous sedation for first trimester surgical abortion in an outpatient clinical setting. Restrictions on moderate intravenous sedation based on BMI alone may be unnecessary., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Long-acting reversible contraceptive (LARC) methods are underutilized in the adolescent population despite their superior efficacy over non-LARC methods. The purpose of this article is to discuss the barriers that lead to underutilization of these methods and present an evidence-based approach for the use of LARC methods among adolescents in the primary care setting.

Background: Induced abortion via dilation and evacuation (D&E) typically involves cervical preparation. Some clinicians also induce fetal death in the second trimester. We designed this study to determine if the combination of intra-amniotic digoxin and osmotic dilators induced intrauterine inflammatory changes., Study Design: Twenty-two women requesting abortion at 19-23 weeks gestation had amniotic fluid sent for measurement of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), white blood cell (WBC) count and anaerobic and aerobic cultures on day 1, before dilators and digoxin amnioinjection. Sampling was repeated on Day 2, prior to D&E., Results: All subjects had significantly elevated IL-6, IL-8 and TNF-α in the amniotic fluid on Day 2. The median difference for IL-6 was 19,893.4 pg/mL (p<.0001), 7040.7 pg/mL (p<.0001) for IL-8 and 181.0 pg/mL (p<.0001) for TNF-α. There was no significant difference in WBC count. There were no clinically significant positive cultures and no clinical infections., Conclusion: The administration of intra-amniotic digoxin and the placement of osmotic dilators prior to D&E create an intrauterine inflammatory response., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Alterations in the cytoskeletal apparatus constitute some of the earliest changes during assumption of an adipogenic phenotype. We examined three major cytoskeletal elements, beta-actin, alpha-tubulin and vimentin, during adipogenesis in euploid cells from human and rat adipose tissue. As reported with 3T3 sub-lines, mRNA level for beta-actin and alpha-tubulin were decreased upon differentiation. However, in contrast to reports with 3T3 cells, levels of vimentin were increased during differentiation. Furthermore, immunological analyses confirmed that there was no decrease in vimentin protein levels during adipogenic development. As well as highlighting a difference between 3T3 cell lines and preadipocytes isolated from fat depots, these studies indicate that the pattern of cytoskeletal gene expression undergoes complex changes early during preadipocyte differentiation.

This study examines the therapeutic outcome of a low plant sterol diet and adjunctive drug therapy (cholestyramine) in the long term treatment of beta-sitosterolemia. A diet restricted in plant sterols, cholesterol and fat was implemented in a 48-year-old male beta-sitosterolemic patient. The plant sterols beta-sitosterol, campesterol and stigmasterol, and cholesterol content of the diet were quantitated by a gas chromatography method (GLC) during metabolic ward studies. Food table analysis of dietary sterols, while quantitatively similar to GLC, significantly underestimated the level of plant sterols and therefore overestimated dietary cholesterol intake. The duration of the study was 18 months. The effect of the diet over a period of 6 months on the sterol levels of plasma and individual lipoprotein fractions (VLDL, LDL, HDL) was evaluated. Apolipoproteins A-1 and B-100 levels were measured. The same parameters were assessed over the next 12 months with the adjunctive use of cholestyramine and dietary restrictions. The diet was effective in lowering total, VLDL, and LDL plant sterols by 37%, 59%, and 32% respectively. The low plant sterol diet did not change total plasma, VLDL or LDL cholesterol. With the addition of cholestyramine, total plasma and LDL cholesterol declined by 64 and 76%, respectively, while HDL-cholesterol remained unchanged. LDL plant sterols declined by 77%, while VLDL plant sterol showed no further change. The decline showed no discrimination among the individual plant sterols. One week after cholestyramine therapy, apolipoprotein B fell from 1.03 to 0.11 g/L, while apolipoprotein A rose from 1.29 to 1.79 g/L. These levels subsequently stabilized at 70% below (0.29 g/L) and 42% above (1.81 g/L) that of diet therapy alone. Xanthomas, angina pectoris, and intermittent claudication resolved during the diet and cholestyramine therapy period. Dietary restriction of plant sterols combined with cholestyramine therapy is an effective means of treating beta-sitosterolemia.

Through their capacity to store fatty acids as triacylglycerol molecules, adipocytes serve a vital physiologic role. This study presents further evidence that this process can be modulated in human adipocytes by the adipsin/acylation stimulating protein (ASP) pathway and suggests a novel function for the product of this system--ASP. The data demonstrate the following: (1) ASP stimulates triacylglycerol synthesis within adipocytes, and this occurs to a greater extent in differentiating than undifferentiated cells (242% +/- 32% vs 168% +/- 11%, p < 0.01, respectively, at an ASP concentration of 88 ng/mL; (2) ASP does not affect the Km for triacylglycerol synthesis but does substantially increase Vmax; (3) when ASP is generated in vitro through incubation of its precursor proteins under appropriate conditions, triacylglycerol synthesis increases to the same extent as when plasma-purified ASP is added to the medium; (4) human adipocytes contain mRNA for the specific serine protease adipsin and the two precursor proteins C3 and factor B required to interact for the production of ASP; and (5) the extent to which cultured differentiating adipocytes produce ASP is proportional to the degree to which they have accumulated triacylglycerol mass during differentiation (r2 = 0.7523, p < 0.0005). These findings provide the first evidence for the existence of the adipsin/ASP pathway in human adipocytes, and this may markedly enhance our understanding of the processes which regulate triacylglycerol clearance from plasma.

The effect of fatty acids on rat adipocyte precursor lipoprotein lipase (LPL) activity was examined. Cellular LPL activity in cultured perirenal precursors reached a maximum after 6 days. At day 6, addition of 10(-8) mol/L oleic acid to the culture medium for 6 hours resulted in a significant reduction of LPL activity. Exposing cultured precursors to 10(-4) mol/L oleic acid caused more than a 50% decrease of intracellular LPL activity measured in either acetone-ether or detergent extracts and more than a 60% decrease of heparin-releasable LPL activity. These reductions were evident within 2.5 hours of exposure to oleic acid, and exposure to oleic acid for as little as 15 minutes caused a subsequent decrease in LPL activity. LPL activity recovered 48 hours after removal of oleic acid from culture medium. Decreased LPL activity after oleic acid exposure was also noted in epididymal cells and in differentiated adipocyte precursors. The extent of decrease of LPL activity upon fatty acid exposure was dependent on the presence of the carboxyl group and was affected by acyl chain length. Although oleic acid did not affect protein synthesis estimated by [3H]-leucine incorporation, LPL mRNA levels were decreased following exposure of cells to oleic acid. Glycerol-3-phosphate dehydrogenase (G3PD) activity and mRNA levels were not affected by oleic acid exposure. Hence, fatty acids cause a dose-, acyl chain-, and carboxyl group-dependent specific decrease of heparin-releasable and intracellular LPL activities in cultured rat adipocyte precursors; this effect is associated with and is likely caused at least in part by a decrease in LPL mRNA levels.

Pursuant to our findings that pituitary basic fibroblast growth factor (bFGF) stimulates the replication of preadipocytes and inhibits their differentiation, we have studied the changes in expression of a bFGF-related mRNA during differentiation. Human omental preadipocytes were grown in primary culture and induced to differentiate with chemically defined serum-free medium. The differentiation process was assessed by monitoring the rise of glycerophosphate dehydrogenase (GPDH) activity, while mRNA expression for a bFGF-related protein(s) and GPDH was examined by amplifying the respective target sequences by polymerase chain reaction. In the case of all cell strains, differentiated preadipocytes revealed much lower expression of bFGF-related mRNA than undifferentiated preadipocytes. Concurrently, the expression of the GPDH mRNA rose significantly. The finding that the expression of the bFGF-related protein is decreased appreciably during adipose differentiation is consonant with its proposed function to expand and maintain adipose cells in a relatively undifferentiated state.

Heparin-binding growth factors related to basic fibroblast growth factor are major determinants of the cellular clonal composition of adipose tissue. By providing and maintaining varying complements of preadipocytes in different fat depots, these factors contribute to the varying sizes and functions of different regions, including the hypercellularity in appreciable obesity. Thus, differing levels and activities of the heparin-binding growth factors contribute to variations in depots within the same individual and between individuals, in lean and obese states. In contrast to regional differences in adiposity, which are accounted by factors resident in adipose tissue, we believe that obesity results from a generalized energy overload. According to our concept, there are genetic variations in cytoskeletal activity and thus differing quantities of energy are utilized for biomechanical processes. In a reciprocal relationship, the higher the cytoskeletal activity, the lesser the energy available for chemical energy storage, mainly in the form of triglyceride in adipocytes. At the extreme of "supermassive" obesity, a mutation in a gene related to a cytoskeletal protein would lead to appreciable dampening of cytoskeletal activity, with consequently the greatest quantity of energy remaining available for eventual triglyceride storage. Moreover, the new concept, for which we have have increasing experimental evidence, invokes a hypothalamic-efferent neural-cytoskeletal pathway, which would modulate the activity of the cytoskeleton.

Paralyzed flagellar mutants pf-1, pf-2, pf-7, and pf-18 of the green alga Chlamydomonas reinhardtii (Dangeard) were shown to store a significantly greater amount of starch than the motile wild type 137c+. The increase in starch storage was significant relative to protein, chlorophyll, and cell number. Analysis of average cell size revealed that the paralyzed mutants were larger than the wild type. This increase in storage molecule accumulation supports an inverse relationship between chemical energy storage and energy utilization for biomechanical/motile cellular functions. Chlamydomonas reinhardtii provides a useful model for studies of the role of cytoskeletal activity in the energy relationship and balance of organisms.

The brain, particularly certain nuclei of the hypothalamus and their neural connections, have a major influence on energy balance, through effects on both food intake and energy expenditure. As summarized in Table 1, there are indeed extensive interactions between the hypothalamus and adipose tissue, the predominate site of storage of chemical energy. Structural, and possibly functional, abnormalities of the neural structures facilitate the development of obesity. This review has described four components of the interactive system. Two of these components are still partly conjectural; while we have increasing experimental support, the hypothalamic-pituitary-adipose axis and the hypothalamic-efferent neural-cytoskeletal pathway are the subject of continuing intense investigation. More complete knowledge of the pathophysiology of obesity will, in turn, facilitate prevention and treatment of corpulence, as well as such frequent associations as non-insulin dependent diabetes mellitus.

A protein released into the culture medium by omental preadipocytes of massively obese persons, which stimulates the replication of rat perirenal preadipocytes, has been purified to a high degree. By gel filtration chromatography, the molecular mass of the mitogenic protein was approximately 66,000 daltons (Da), while on sodium dodecyl sulfate - polyacrylamide gel electrophoresis, two subunits were obtained, relative masses (Mr) of approximately 31,000 and approximately 35,000. The isoelectric point of the approximately 66,000 Da entity was 5.6 +/- 0.2. By specific radioreceptor assay, the purified protein was related to epidermal growth factor and transforming growth factor alpha. It was not related to insulin-like growth factors I and II by radioimmunoassay and radioreceptor assay. We propose that the approximately 66,000 Mr protein, and other mitogenic proteins released by preadipocytes from massively obese persons, act through paracrine-autocrine mechanisms and may play a role in the development of the hyperplasia of enlarged fat cells characteristic of massive corpulence.

The process of adipose differentiation uniquely endows fat cells to accrue triacylglycerols under conditions of nutrient energy surfeit and to release fatty acids during energy deprivation. The object of this investigation was to study influences on this process in perirenal preadipocytes, grown in primary culture or first subculture and derived from male Sprague-Dawley rats, 180-200 g. Supplementation of the culture medium with 1-methyl-3-isobutylxanthine, corticosterone, and insulin induced differentiation in practically all perirenal preadipocytes, as indicated morphologically and by rising glycerophosphate dehydrogenase activity. Appreciable differentiation was induced even in the absence of methylisobutylxanthine. Transforming growth factor beta (1-1000 pM), cachectin (tumour necrosis factor alpha) (1-1000 pM), and basic fibroblast growth factor (0.063-63 nM) inhibited adipose differentiation significantly, almost completely at the higher concentrations. Direct inhibition, rather than a persisting mitogenic effect of fibroblast growth factor, was confirmed using demecolcine (Colcemid). The fact that transforming growth factor beta and cachectin inhibit differentiation in preadipocytes from postpubertal rats suggests that this effect probably also occurs in vivo, thus diverting energy from adipose depots in certain neoplastic and inflammatory states. We propose that the anterior pituitary, through fibroblast growth factor(s), modulates the pool of preadipocytes and other mesenchymal cells. The mitogenic effect would be complemented by a concerted function, inhibition of adipose differentiation, resulting in the retention of a greater number of potentially replicative cells. Then, depending on the subject's nutritional and endocrine status, extrapituitary factors would regulate the specific process of differentiation.

Adipose cells grown in sub-culture are useful to elucidate genetic factors in obesity. Most omental adipose cell strains from 140 massively obese (greater than 170 percent of reference body weight) subjects replicated, in successive sub-cultures, to a significantly higher degree than cells from lean or moderately obese persons. The difference was due to a greater number of rapidly dividing clones. Adipose cells from the massively obese related into the culture medium proteins, native Mr 20,000-65,000, mitogenic on rat preadipocytes. Mitogenic activity of the medium was much less evident with cells from the lean. In the case of several cell strains, culture with 17-beta-estradiol increased the mitogenic activity of the medium. Omental adipose tissue of the massive obese also contained a greater number of adipose cell clones susceptible to differentiation. Hybrids of adipose cells from the massively obese fused with murine renal adenocarcinoma cells (RAG) revealed more prominent differentiation than hybrids comprised of adipose cells from the lean. Further, only those comprised of adipose cells from the obese could recapitulate differentiation in sub-cultures. These findings in culture probably reflect major heritable factors that facilitate the development of massive obesity in humans.

We have raised a monkey antiserum that is selectively reactive with human leukemic myeloblasts by immunization with a glycoprotein antigen (AMLSGA) released from myeloblasts in short-term culture. Antimyeloblast activity can be demonstrated using complement-dependent cytotoxicity or indirect immunofluorescence. Selective antimyeloblast activity is retained following absorption with leukemic lymphoblasts or lymphocytes, nonleukemic lymphocytes, neutrophils, or mononuclear cells from nonleukemic bone marrow. Anti-AMLSGA antisera are not reactive with B-cell-enriched cell populations, and antaimyeloblast activity is not reduced by absorption with Ia-positive cells. Anti-AMLSGA is a useful reagent for identification of human leukemic myeloblasts.

When propionyl-CoA was substituted for either acetyl-CoA or butyryl-CoA in the presence of [14C]malonyl-CoA and NADPH, the pure human liver fatty acids synthetase complex synthesized only straight-chain, saturated, 15- and 17-carbon radioactive fatty acids. At optimal concentrations, propionyl-CoA was a better primer of fatty acid synthesis than acetyl-CoA. Methylmalonyl-CoA inhibited the synthetase competitively with respect to malonyl-CoA. The Ki was calculated to be 8.4 muM. These findings provide an in vitro model and offer a direct explanation at the molecular level for some of the abnormal manifestations observed in diseases characterized by increased cellular concentrations of propionyl-CoA and methylmalonyl-CoA.