Gabapentin for pain management after osmotic dilator insertion and prior to dilation and evacuation: A randomized controlled trial.

ObjectiveTo evaluate if gabapentin 600 mg reduces pain after osmotic dilator placement the day before a dilation and evacuation (D&E) procedure.Study designWe conducted a double-blind, placebo-controlled, randomized (stratified by vaginal parity) trial among women undergoing osmotic dilator placement before D&E at 15-23 5/7 weeks gestation. Subjects received gabapentin 600 mg or placebo 30 min before dilator placement, with re-dosing 8 h later. We assessed pain after dilator placement using a numeric rating scale (NRS; scale 0-10) at 5 min, 2, 4, and 8 h, and at presentation for D&E. The primary outcome was median NRS pain score change from baseline to 8 h after dilator placement. Secondary outcomes included gabapentin-related side effects and analgesic use.ResultsOf 121 randomized women, we excluded three subjects (allergic reaction [placebo], randomization error, no NRS data), leaving 60 gabapentin and 58 placebo subjects. Of 110 (93%) women who provided 8-hour data, median pain score changes from baseline did not differ between gabapentin and placebo groups overall (2 vs. 2.5, p = 0.52), in vaginally nulliparous women (2 vs. 4, p = 0.10) or in parous women (2 vs. 1.5, p = 0.37). We found no statistically significant differences in median pain score change from baseline to any timepoint overall or when stratified by parity. Beginning at 2 h after dilator placement, more gabapentin than placebo users experienced dizziness (29/53[55%] vs. 11/53[21%], p = 0.001) and tiredness (34/54[63%] vs. 17/54[31%], p = 0.002). The proportion of women using narcotics did not differ between gabapentin (35/60[58%]) or placebo (40/58[69%]) users (p = 0.26).ConclusionsGabapentin does not reduce pain with overnight osmotic dilator placement prior to D&E and causes drug-related side effects.Implications statementWomen experience pain, mostly mild to moderate, with overnight cervical dilator placement at 15-23 5/7 weeks gestation. About 2/3 of women will use a limited quantity of narcotics if provided. Gabapentin does not decrease the pain with or following dilator placement and does not decrease narcotic use

Mifepristone Antagonization With Progesterone to Prevent Medical Abortion: A Randomized Controlled Trial.

ObjectiveTo estimate the efficacy and safety of mifepristone antagonization with high-dose oral progesterone.MethodsWe planned to enroll 40 patients in a double-blind, placebo-controlled, randomized trial. We enrolled patients at 44-63 days of gestation with ultrasound-confirmed gestational cardiac activity who were planning surgical abortion. Participants ingested mifepristone 200 mg and initiated oral progesterone 400 mg or placebo 24 hours later twice daily for 3 days, then once daily until their planned surgical abortion 14-16 days after enrollment. Follow-up visits were scheduled 3±1, 7±1, and 15±1 days after mifepristone intake with ultrasonography and blood testing for human chorionic gonadotropin and progesterone. Participants exited from the study when they had their surgical abortion or earlier for gestational cardiac activity absence, gestational sac expulsion, or medically indicated suction aspiration. We assessed the primary outcome of continued gestational cardiac activity at approximately 2 weeks (15±1 day), side effects after drug ingestion, and safety outcomes including hemorrhage and emergent treatment.ResultsWe enrolled participants from February to July 2019 and stopped enrollment after 12 patients for safety concerns. Mean gestational age was 52.5 days. Two (one per group) voluntarily discontinued 3 days after mifepristone ingestion for subjective symptoms (nausea and vomiting, bleeding). Among the remaining 10 patients (five per group), gestational cardiac activity continued for 2 weeks in four in the progesterone group and two in the placebo group. One patient in the placebo group had no gestational cardiac activity 3 days after mifepristone use. Severe hemorrhage requiring ambulance transport to hospital occurred in three patients; one received progesterone (complete expulsion, no aspiration) and two received placebo (aspiration for both, one required transfusion). We halted enrollment after the third hemorrhage. No other significant side effects were reported.ConclusionWe could not estimate the efficacy of progesterone for mifepristone antagonization due to safety concerns when mifepristone is administered without subsequent prostaglandin analogue treatment. Patients in early pregnancy who use only mifepristone may be at high risk of significant hemorrhage.Clinical trial registrationClinicalTrials.gov, NCT03774745

Identifying fungal-host associations in an amphibian host system

Host-associated microbes can interact with macro-organisms in a number of ways that affect host health. Few studies of host-associated microbiomes, however, focus on fungi. In addition, it is difficult to discern whether a fungal organism found in or on an ectotherm host is associating with it in a durable, symbiotic interaction versus a transient one, and to what extent the habitat and host share microbes. We seek to identify these host-microbe interactions on an amphibian, the Colorado boreal toad (Anaxyrus boreas boreas). We sequenced the ITS1 region of the fungal community on the skin of wild toads (n = 124) from four sites in the Colorado Rocky Mountains, across its physiologically dynamic developmental life stages. We also sampled the common habitats used by boreal toads: water from their natal wetland and aquatic pond sediment. We then examined diversity patterns within different life stages, between host and habitat, and identified fungal taxa that could be putatively host-associated with toads by using an indicator species analysis on toad versus environmental samples. Host and habitat were strikingly similar, with the exception of toad eggs. Post-hatching toad life stages were distinct in their various fungal diversity measures. We identified eight fungal taxa that were significantly associated with eggs, but no other fungal taxa were associated with other toad life stages compared with their environmental habitat. This suggests that although pre- and post-metamorphic toad life stages differ from each other, the habitat and host fungal communities are so similar that identifying obligate host symbionts is difficult with the techniques used here. This approach does, however, leverage sequence data from host and habitat samples to predict which microbial taxa are host-associated versus transient microbes, thereby condensing a large set of sequence data into a smaller list of potential targets for further consideration. &nbsp;</p

Immunoproteasome Overexpression Underlies the Pathogenesis of Thyroid Oncocytes and Primary Hypothyroidism: Studies in Humans and Mice

BACKGROUND:Oncocytes of the thyroid gland (Hürthle cells) are found in tumors and autoimmune diseases. They have a unique appearance characterized by abundant granular eosinophilic cytoplasm and hyperchromatic nucleus. Their pathogenesis has remained, thus far, unknown. METHODOLOGY/PRINCIPAL FINDINGS:Using transgenic mice chronically expressing IFNgamma in thyroid gland, we showed changes in the thyroid follicular epithelium reminiscent of the human oncocyte. Transcriptome analysis comparing transgenic to wild type thyrocytes revealed increased levels of immunoproteasome subunits like LMP2 in transgenics, suggesting an important role of the immunoproteasome in oncocyte pathogenesis. Pharmacologic blockade of the proteasome, in fact, ameliorated the oncocytic phenotype. Genetic deletion of LMP2 subunit prevented the development of the oncocytic phenotype and primary hypothyroidism. LMP2 was also found expressed in oncocytes from patients with Hashimoto thyroiditis and Hürthle cell tumors. CONCLUSIONS/SIGNIFICANCE:In summary, we report that oncocytes are the result of an increased immunoproteasome expression secondary to a chronic inflammatory milieu, and suggest LMP2 as a novel therapeutic target for the treatment of oncocytic lesions and autoimmune hypothyroidism

In everlasting fight against academic procrastination: The roles of classroom engagement and internal locus of control

This study aims to test the hypothesis that classroom engagement mediates the relationship between students’ internal locus of control and academic procrastination. As many as 302 students from a private university between 18 to 26 years of age were recruited to respond to Internal-External Locus of control Scale, Classroom Engagement Inventory, and Academic Procrastination scale. Bootstrapping analyses were conducted by utilizing PROCESS Macro model 4 in SPSS software, and the results showed that the mediator variable fully mediates the link between the predictor and outcome variables. In other words, the direct effect of internal locus of control on academic procrastination was no longer significant when controlling for classroom engagement. Further discussion, implications and suggestions were presented at the end of the article

Standardized Neon Organismal Data for Biodiversity Research

Understanding patterns and drivers of species distribution and abundance, and thus biodiversity, is a core goal of ecology. Despite advances in recent decades, research into these patterns and processes is currently limited by a lack of standardized, high-quality, empirical data that span large spatial scales and long time periods. The NEON fills this gap by providing freely available observational data that are generated during robust and consistent organismal sampling of several sentinel taxonomic groups within 81 sites distributed across the United States and will be collected for at least 30 years. The breadth and scope of these data provide a unique resource for advancing biodiversity research. To maximize the potential of this opportunity, however, it is critical that NEON data be maximally accessible and easily integrated into investigators\u27 workflows and analyses. To facilitate its use for biodiversity research and synthesis, we created a workflow to process and format NEON organismal data into the ecocomDP (ecological community data design pattern) format that were available through the ecocomDP R package; we then provided the standardized data as an R data package (neonDivData). We briefly summarize sampling designs and data wrangling decisions for the major taxonomic groups included in this effort. Our workflows are open-source so the biodiversity community may: add additional taxonomic groups; modify the workflow to produce datasets appropriate for their own analytical needs; and regularly update the data packages as more observations become available. Finally, we provide two simple examples of how the standardized data may be used for biodiversity research. By providing a standardized data package, we hope to enhance the utility of NEON organismal data in advancing biodiversity research and encourage the use of the harmonized ecocomDP data design pattern for community ecology data from other ecological observatory networks

Hubble Space Telescope and Ground-Based Observations of the Type Iax Supernovae SN 2005hk and SN 2008A

We present Hubble Space Telescope (HST) and ground-based optical and near-infrared observations of SN 2005hk and SN 2008A, typical members of the Type Iax class of supernovae (SNe). Here we focus on late-time observations, where these objects deviate most dramatically from all other SN types. Instead of the dominant nebular emission lines that are observed in other SNe at late phases, spectra of SNe 2005hk and 2008A show lines of Fe II, Ca II, and Fe I more than a year past maximum light, along with narrow [Fe II] and [Ca II] emission. We use spectral features to constrain the temperature and density of the ejecta, and find high densities at late times, with n_e >~ 10^9 cm^-3. Such high densities should yield enhanced cooling of the ejecta, making these objects good candidates to observe the expected "infrared catastrophe," a generic feature of SN Ia models. However, our HST photometry of SN 2008A does not match the predictions of an infrared catastrophe. Moreover, our HST observations rule out a "complete deflagration" that fully disrupts the white dwarf for these peculiar SNe, showing no evidence for unburned material at late times. Deflagration explosion models that leave behind a bound remnant can match some of the observed properties of SNe Iax, but no published model is consistent with all of our observations of SNe 2005hk and 2008A.Comment: 20 pages, 15 figure

LSQ13ddu: a rapidly evolving stripped-envelope supernova with early circumstellar interaction signatures

This paper describes the rapidly evolving and unusual supernova LSQ13ddu, discovered by the La Silla-QUEST survey. LSQ13ddu displayed a rapid rise of just 4.8 ± 0.9 d to reach a peak brightness of −19.70 ± 0.02 mag in the LSQgr band. Early spectra of LSQ13ddu showed the presence of weak and narrow HeI features arising from interaction with circumstellar material (CSM). These interaction signatures weakened quickly, with broad features consistent with those seen in stripped-envelope SNe becoming dominant around two weeks after maximum. The narrow HeI velocities are consistent with the wind velocities of luminous blue variables but its spectra lack the typically seen hydrogen features. The fast and bright early light curve is inconsistent with radioactive ⁵⁶Ni powering but can be explained through a combination of CSM interaction and an underlying ⁵⁶Ni decay component that dominates the later time behaviour of LSQ13ddu. Based on the strength of the underlying broad features, LSQ13ddu appears deficient in He compared to standard SNe Ib