Abortion Policies in U.S. Teaching Hospitals: Formal and Informal Parameters Beyond the Law.

OBJECTIVE: To evaluate the prevalence and features of policies regulating abortion in U.S. teaching hospitals. METHODS: In this mixed-methods study, we conducted a national survey of obstetrics and gynecology teaching hospitals (2015-2016) and qualitative interviews (2014 and 2017) with directors at obstetrics and gynecology residency programs. We asked participants about hospital regulations on abortion and their perceptions of the nature and enforcement of these policies. Interview analysis was conducted with a grounded theoretical approach and informed development of the survey. The prevalence of policies was described using survey data; differences in policy structures by region were analyzed using a series of logistic regression models. RESULTS: Directors from 169 of 231 eligible training programs responded to the survey (73%). Institutional policies limited abortion beyond state law in 57% of teaching hospitals, most commonly in the Midwest and South (odds ratio [OR] 4.3, P<.01 for Midwest; OR 4.0, P=.001 for South vs Northeast). Policies varied in form (written and unwritten) and restricted abortion based on the indication for the procedure and gestational age. Nonmedically indicated, or "elective" procedures were more commonly restricted (48% of sites reporting any policy and 25% prohibiting these abortions altogether) than medically indicated ones (28% of sites reporting any policy.) Policies were created by those with institutional power, including hospital leadership and obstetrics and gynecology department chairs, and were perceived to be motivated by personal beliefs and a desire to avoid controversy. Rules were commonly enforced by medical specialists, hospital ethics committees, and department chairs. Qualitative data highlighted the convoluted nuances of these policies, which often put clinicians at odds with their professional mandates. DISCUSSION: Reportedly driven by broader institutional interests, obstetrics and gynecology teaching hospital policies often restricted abortion beyond state law to the detriment of abortion access and training opportunities. Vague or unwritten abortion policies, although difficult to navigate, gave health care providers some agency and flexibility over their practices.

Placental syncytium forms a biophysical barrier against pathogen invasion.

Fetal syncytiotrophoblasts form a unique fused multinuclear surface that is bathed in maternal blood, and constitutes the main interface between fetus and mother. Syncytiotrophoblasts are exposed to pathogens circulating in maternal blood, and appear to have unique resistance mechanisms against microbial invasion. These are due in part to the lack of intercellular junctions and their receptors, the Achilles heel of polarized mononuclear epithelia. However, the syncytium is immune to receptor-independent invasion as well, suggesting additional general defense mechanisms against infection. The difficulty of maintaining and manipulating primary human syncytiotrophoblasts in culture makes it challenging to investigate the cellular and molecular basis of host defenses in this unique tissue. Here we present a novel system to study placental pathogenesis using murine trophoblast stem cells (mTSC) that can be differentiated into syncytiotrophoblasts and recapitulate human placental syncytium. Consistent with previous results in primary human organ cultures, murine syncytiotrophoblasts were found to be resistant to infection with Listeria monocytogenes via direct invasion and cell-to-cell spread. Atomic force microscopy of murine syncytiotrophoblasts demonstrated that these cells have a greater elastic modulus than mononuclear trophoblasts. Disruption of the unusually dense actin structure--a diffuse meshwork of microfilaments--with Cytochalasin D led to a decrease in its elastic modulus by 25%. This correlated with a small but significant increase in invasion of L. monocytogenes into murine and human syncytium. These results suggest that the syncytial actin cytoskeleton may form a general barrier against pathogen entry in humans and mice. Moreover, murine TSCs are a genetically tractable model system for the investigation of specific pathways in syncytial host defenses.

Tissue barriers of the human placenta to infection with Toxoplasma gondii.

Toxoplasma gondii is a ubiquitous, obligate intracellular parasite capable of crossing the placenta to cause spontaneous abortion, preterm labor, or significant disease in the surviving neonate. Exploration of the cellular and histological components of the placental barrier is in its infancy, and both how and where T. gondii breaches it are unknown. The human placenta presents two anatomical interfaces between maternal cells and fetal cells (trophoblasts): (i) the villous region where maternal blood bathes syncytialized trophoblasts for nutrient exchange and (ii) the maternal decidua, where mononuclear, extravillous trophoblasts anchor the villous region to the uterus. Using first-trimester human placental explants, we demonstrate that the latter site is significantly more vulnerable to infection, despite presenting a vastly smaller surface. This is consistent with past findings concerning two vertically transmitted viruses and one bacterium. We further explore whether three genetically distinct T. gondii types (I, II, and III) are capable of preferential placental infection and survival in this model. We find no difference in these strains' ability to infect placental explants; however, slightly slower growth is evident in type II (Prugniaud [Pru]) parasites relative to other cell types, although this did not quite achieve statistical significance.

Invasive extravillous trophoblasts restrict intracellular growth and spread of Listeria monocytogenes.

Listeria monocytogenes is a facultative intracellular bacterial pathogen that can infect the placenta, a chimeric organ made of maternal and fetal cells. Extravillous trophoblasts (EVT) are specialized fetal cells that invade the uterine implantation site, where they come into direct contact with maternal cells. We have shown previously that EVT are the preferred site of initial placental infection. In this report, we infected primary human EVT with L. monocytogenes. EVT eliminated ∼80% of intracellular bacteria over 24-hours. Bacteria were unable to escape into the cytoplasm and remained confined to vacuolar compartments that became acidified and co-localized with LAMP1, consistent with bacterial degradation in lysosomes. In human placental organ cultures bacterial vacuolar escape rates differed between specific trophoblast subpopulations. The most invasive EVT-those that would be in direct contact with maternal cells in vivo-had lower escape rates than trophoblasts that were surrounded by fetal cells and tissues. Our results suggest that EVT present a bottleneck in the spread of L. monocytogenes from mother to fetus by inhibiting vacuolar escape, and thus intracellular bacterial growth. However, if L. monocytogenes is able to spread beyond EVT it can find a more hospitable environment. Our results elucidate a novel aspect of the maternal-fetal barrier.

Placental syncytiotrophoblast constitutes a major barrier to vertical transmission of Listeria monocytogenes.

Listeria monocytogenes is an important cause of maternal-fetal infections and serves as a model organism to study these important but poorly understood events. L. monocytogenes can infect non-phagocytic cells by two means: direct invasion and cell-to-cell spread. The relative contribution of each method to placental infection is controversial, as is the anatomical site of invasion. Here, we report for the first time the use of first trimester placental organ cultures to quantitatively analyze L. monocytogenes infection of the human placenta. Contrary to previous reports, we found that the syncytiotrophoblast, which constitutes most of the placental surface and is bathed in maternal blood, was highly resistant to L. monocytogenes infection by either internalin-mediated invasion or cell-to-cell spread. Instead, extravillous cytotrophoblasts-which anchor the placenta in the decidua (uterine lining) and abundantly express E-cadherin-served as the primary portal of entry for L. monocytogenes from both extracellular and intracellular compartments. Subsequent bacterial dissemination to the villous stroma, where fetal capillaries are found, was hampered by further cellular and histological barriers. Our study suggests the placenta has evolved multiple mechanisms to resist pathogen infection, especially from maternal blood. These findings provide a novel explanation why almost all placental pathogens have intracellular life cycles: they may need maternal cells to reach the decidua and infect the placenta.

Synthesis, characterization, and electrocatalytic activity of PtPb nanoparticles prepared by two synthetic approaches.

Intermetallic PtPb nanoparticles have been synthesized by two solution-phase reduction methods. In the first (PtPb-B), Pt and Pb salts were reduced by sodium borohydride in methanol at room temperature. In the second (PtPb-N), metal-organic Pt and Pb precursors were reduced by sodium naphthalide in diglyme at 135 degrees C. Both methods produced small agglomerated nanoparticles of the ordered intermetallic PtPb (mean crystal domain size <15 nm) which were characterized by pXRD, SEM, UHV-STEM, BET, EDX, and electron diffraction. The electrocatalytic activity of PtPb nanoparticles produced by both methods toward formic acid and methanol oxidation was investigated and compared to Pt and PtRu. Both PtPb-B and PtPb-N nanoparticles exhibited enhanced electrocatalytic activity compared to commercially available Pt black and PtRu nanoparticles. For formic acid oxidation, the PtPb nanoparticles exhibited considerably lower onset potentials and higher current densities than Pt or PtRu. For methanol oxidation, the PtPb nanoparticles had onset potentials slightly positive of PtRu but exhibited higher current densities at potentials about 100 mV positive of onset. The general applicability of these methods for the synthesis of nanoparticles of ordered intermetallic phases is discussed.

Circulating immune complexes and autoantibodies in canine leishmaniasis.

In sera of 35 dogs with generalised leishmaniasis elevated levels of circulating immune complexes were detected by the 125I-C1q binding test. Furthermore, anti-heart muscle and anti-smooth muscle antibodies were detected by an indirect immunofluorescence technique in sera of infected dogs.

Effects of plasma-exchange on complement-mediated solubilization of circulating immune complexes in patients with systemic lupus erythematosus.

In an uncontrolled clinical trial the effects of plasma-exchange (PE) on the capacity of the serum to solubilize circulating immune complexes were studied in patients with active systemic lupus erythematosus. Four patients were treated with immunosuppressive therapy alone, while others were also treated by PE over a period of four to seven weeks. Plasma was replaced by fresh frozen plasma in the final part of each procedure. All patients showed evidence of clinical improvement at the time of treatment. Furthermore, PE was demonstrated to reduce drastically the number of relapses. An improvement of the capacity of solubilize immune complexes in vitro associated with a persistent fall in the levels of the circulating immune complexes was observed in patients treated with PE. This suggests that fresh frozen plasma improves the clearance of immune complexes and reduces the frequency of relapses. In our experience, clinical improvement and/or resolution of the symptoms seems to be related to the decrease in serum immune complex levels, while clinical relapses seem to parallel the behaviour of complement-mediated solubilization.