bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining long-term trends in politics and culture through language of political leaders and cultural institutions
Authors: Jordan Kayla N. , Sterling Joanna , Pennebaker James W. , Boyd Ryan L.
Published: February 2019

Significance

Donald Trump and a small group of emerging leaders around the world have been labeled as outliers in the ways that they think and communicate with others. Are they really anomalies, or do they fit into larger political trends? This study adds to existing scholarship by analyzing two important psychological dimensions, analytic thinking and confidence, in 12 large corpora of political texts representing political leaders of various levels in both the United States and other countries as well as 4 corpora of cultural texts. Rather than being anomalous, linguistic analyses find that, over the last century, there have been consistent declines in analytic thinking and rises in confidence in the ways that political leaders communicate with the public.
From 2D to 3D: Strain- and elongation-free topological transformations of optoelectronic circuits
Authors: Fan Dejiu , Lee Byungjun , Coburn Caleb , Forrest Stephen R.
Published: February 2019

Significance

We demonstrate a general method to transform planar electronic and optoelectronic devices fabricated by conventional photolithography into a strain-free but topologically different geometry. The method is used to demonstrate hemispherical, retina-like imagers whose pixel spacings are unaffected by the topological transformation. Our approach overcomes the critical limitation of distortion encountered in transforming a planar circuit to a nondevelopable, 3D shape. The process opens up additional possibilities for making a variety of electronic circuits that conform to randomly shaped surfaces, including high resolution, and large field of view imagers that have the shape and form factor of the human eye.
Inhibition of EZH2 prevents fibrosis and restores normal angiogenesis in scleroderma
Authors: Tsou Pei-Suen , Campbell Phillip , Amin M. Asif , Coit Patrick , Miller Shaylynn , Fox David A. , Khanna Dinesh , Sawalha Amr H.
Published: February 2019

Significance

The key epigenetic regulator EZH2 plays a central role in fibrosis and abnormal angiogenesis in scleroderma. EZH2-target genes mediating profibrotic and antiangiogenic effects in scleroderma patients have been identified and characterized. Inhibiting EZH2 by repurposing already-existing EZH2 inhibitors currently being trialed in cancer might provide a therapeutic approach to scleroderma.
Tyramine action on motoneuron excitability and adaptable tyramine/octopamine ratios adjust
Drosophila
locomotion to nutritional state
Authors: Schützler Natalie , Girwert Chantal , Hügli Isabell , Mohana Giriram , Roignant Jean-Yves , Ryglewski Stefanie , Duch Carsten
Published: February 2019

Significance

Biogenic amines, like norepinephrine, can act as neuromodulators to render animal behavior adaptive to changing external and internal conditions. The
Drosophila
genetic model system has been used extensively to identify aminergic neurons which modulate cognitive, emotional, and motor behaviors, but the cellular targets and physiological consequences of aminergic modulation remain poorly understood. We show that nutritional state affects amine biosynthesis to tune the relative levels of octopamine and tyramine in central
Drosophila
neurons. Starvation increases octopamine and locomotion, whereas satiation increases tyramine, which acts directly on motoneurons to decrease L-type calcium current and excitability. Both effects are required to adjust locomotor behavior to nutritional state. Therefore, adaptive behavior can be controlled on the level of motoneuron modulation and amine biosynthesis.
Epigenomic analysis reveals DNA motifs regulating histone modifications in human and mouse
Authors: Ngo Vu , Chen Zhao , Zhang Kai , Whitaker John W. , Wang Mengchi , Wang Wei
Published: February 2019

Significance

How the locus-specific histone modifications are achieved is not fully understood. One of the contributing mechanisms is that DNA binding molecules recognize specific sequences and their binding recruits or stabilizes the histone modification enzyme complexes. Comprehensive identification of such sequence patterns is the first step toward revealing possible regulatory grammar for establishing histone modifications. In this study, we have cataloged the DNA motifs tightly associated with six and eight important histone modifications in human and mouse, respectively. We show that mutating the found motifs at particular loci led to significant reduction of the histone modification levels. These histone-associated motifs, especially H3K4me3 motifs, significantly overlap with expression of quantitative trait loci SNPs in cancer patients more than known motifs, further suggesting their regulatory roles. We also found possible feedback loops mediated by these motifs, implicating their possible roles in histone modification dynamics and epigenetic priming.
Mindfulness training reduces loneliness and increases social contact in a randomized controlled trial
Authors: Lindsay Emily K. , Young Shinzen , Brown Kirk Warren , Smyth Joshua M. , Creswell J. David
Published: February 2019

Significance

Loneliness (i.e., feeling alone) and social isolation (i.e., being alone) are among the most robust known risk factors for poor health and accelerated mortality. Yet mitigating these social risk factors is challenging, as few interventions have been effective for both reducing loneliness and increasing social contact. Mindfulness interventions, which train skills in monitoring present-moment experiences with an orientation of acceptance, have shown promise for improving social-relationship processes. This study demonstrates the efficacy of a 2-wk smartphone-based mindfulness training for reducing loneliness and increasing social contact in daily life. Importantly, this study shows that developing an orientation of acceptance toward present-moment experiences is a critical mechanism for mitigating these social risk factors.
Western diet regulates immune status and the response to LPS-driven sepsis independent of diet-associated microbiome
Authors: Napier Brooke A. , Andres-Terre Marta , Massis Liliana M. , Hryckowian Andrew J. , Higginbottom Steven K. , Cumnock Katherine , Casey Kerriann M. , Haileselassie Bereketeab , Lugo Kyler A. , Schneider David S. , Sonnenburg Justin L. , Monack Denise M.
Published: February 2019

Significance

The Western diet (WD) is high in fats and sucrose and low in fiber and is the most prevalent diet in westernized countries. We find that in our model of sepsis, mice fed WD had increased sepsis severity and poorer outcomes. WD-fed mice had higher baseline inflammation, increased sepsis-associated immunoparalysis, and altered neutrophil populations in the blood. The WD-dependent increase in sepsis severity and mortality was independent of the diet-associated microbiome, suggesting that diet may be directly regulating innate immunity. We used our identified disease factors and found WD-fed mice occupy a unique path in sepsis disease progression. Our data provide insight into diet-dependent reprogramming of the immune response and will be important in treating and diagnosing a WD-fed population.
Snapshot of an oxygen intermediate in the catalytic reaction of cytochromecoxidase
Authors: Ishigami Izumi , Lewis-Ballester Ariel , Echelmeier Austin , Brehm Gerrit , Zatsepin Nadia A. , Grant Thomas D. , Coe Jesse D. , Lisova Stella , Nelson Garrett , Zhang Shangji , Dobson Zachary F. , Boutet Sébastien , Sierra Raymond G. , Batyuk Alexander , Fromme Petra , Fromme Raimund , Spence John C. H. , Ros Alexandra , Yeh Syun-Ru , Rousseau Denis L.
Published: February 2019

Cytochromecoxidase (CcO) reduces dioxygen to water and harnesses the chemical energy to drive proton translocation across the inner mitochondrial membrane by an unresolved mechanism. By using time-resolved serial femtosecond crystallography, we identified a key oxygen intermediate of bovine CcO. It is assigned to the PR-intermediate, which is characterized by specific redox states of the metal centers and a distinct protein conformation. The hemea3iron atom is in a ferryl (Fe4+= O2−) configuration, and hemeaand CuBare oxidized while CuAis reduced. A Helix-X segment is poised in an open conformational state; the hemeafarnesyl sidechain is H-bonded to S382, and loop-I-II adopts a distinct structure. These data offer insights into the mechanism by which the oxygen chemistry is coupled to unidirectional proton translocation.
Cold sensing by Na
V
1.8-positive and Na
V
1.8-negative sensory neurons
Authors: Luiz A. P. , MacDonald D. I. , Santana-Varela S. , Millet Q. , Sikandar S. , Wood J. N. , Emery E. C.
Published: February 2019

Significance

The cellular correlate for cold sensing has been ascribed to either Trpm8-expressing or Na
V
1.8-expressing neurons. Importantly, transcriptomic analysis shows that these neuronal populations are nonoverlapping. Using in vivo GCaMP imaging in live mice we show that the vast majority of acute cold-sensing neurons activated at ≥1 °C do not express Na
V
1.8, and that the loss of Na
V
1.8 does not affect acute cold-sensing behavior in mice. Instead, we show that cold-responding neurons are enriched with Trpm8 as well as numerous potassium channels, including Kcnk9. By contrast, Na
V
1.8-positive neurons signal prolonged extreme cold. These observations highlight the complexity of cold sensing in DRG neurons, and the role of Na
V
1.8-negative neurons in cold sensing down to 1 °C.
Organism motility in an oxygenated shallow-marine environment 2.1 billion years ago
Authors: El Albani Abderrazak , Mangano M. Gabriela , Buatois Luis A. , Bengtson Stefan , Riboulleau Armelle , Bekker Andrey , Konhauser Kurt , Lyons Timothy , Rollion-Bard Claire , Bankole Olabode , Lekele Baghekema Stellina Gwenaelle , Meunier Alain , Trentesaux Alain , Mazurier Arnaud , Aubineau Jeremie , Laforest Claude , Fontaine Claude , Recourt Philippe , Chi Fru Ernest , Macchiarelli Roberto , Reynaud Jean Yves , Gauthier-Lafaye François , Canfield Donald E.
Published: February 2019

Significance

The 2.1 billion-year-old sedimentary strata contain exquisitely preserved fossils that provide an ecologic snapshot of the biota inhabiting an oxygenated shallow-marine environment. Most striking are the pyritized string-shaped structures, which suggest that the producer have been a multicellular or syncytial organism able to migrate laterally and vertically to reach for food resources. A modern analogue is the aggregation of amoeboid cells into a migratory slug phase in modern cellular slime molds during time of food starvation. While it remains uncertain whether the amoeboidlike organisms represent a failed experiment or a prelude to subsequent evolutionary innovations, they add to the growing record of comparatively complex life forms that existed more than a billion years before animals emerged in the late Neoproterozoic.
Bacterial lipolysis of immune-activating ligands promotes evasion of innate defenses
Authors: Chen Xi , Alonzo Francis
Published: February 2019

Significance

Microbial adaptation to the host environment is crucial for commensalism and pathogenesis. One adaptive strategy includes the production of lipolytic enzymes that allow acquisition of free fatty acids and disruption of lipid barriers. We demonstrate that a secreted lipase of
Staphylococcus aureus
also facilitates immune evasion by inactivating bacterial-derived lipoproteins, a pathogen-associated molecular pattern required for innate immune activation. Lipase activity changes the local inflammatory environment and promotes bacterial survival during infection. Thus, this work provides evidence that bacterial lipases can have unappreciated roles in immunomodulation. While many
S. aureus
-secreted virulence factors exert their effects directly on host cells, our study provides an interesting example of a bacterial enzyme that acts on endogenous substrates to mask immune recognition.
Kinetics of trifurcated electron flow in the decaheme bacterial proteins MtrC and MtrF
Authors: Jiang Xiuyun , Burger Bastian , Gajdos Fruzsina , Bortolotti C. , Futera Zdenek , Breuer Marian , Blumberger Jochen
Published: February 2019

The bacterium
Shewanella oneidensis
has evolved a sophisticated electron transfer (ET) machinery to export electrons from the cytosol to extracellular space during extracellular respiration. At the heart of this process are decaheme proteins of the Mtr pathway, MtrC and MtrF, located at the external face of the outer bacterial membrane. Crystal structures have revealed that these proteins bind 10 c-type hemes arranged in the peculiar shape of a staggered cross that trifurcates the electron flow, presumably to reduce extracellular substrates while directing electrons to neighboring multiheme cytochromes at either side along the membrane. Especially intriguing is the design of the heme junctions trifurcating the electron flow: they are made of coplanar and T-shaped heme pair motifs with relatively large and seemingly unfavorable tunneling distances. Here, we use electronic structure calculations and molecular simulations to show that the side chains of the heme rings, in particular the cysteine linkages inserting in the space between coplanar and T-shaped heme pairs, strongly enhance electronic coupling in these two motifs. This results in an

≈

10

3

-fold speedup of ET steps at heme junctions that would otherwise be rate limiting. The predicted maximum electron flux through the solvated proteins is remarkably similar for all possible flow directions, suggesting that MtrC and MtrF shuttle electrons with similar efficiency and reversibly in directions parallel and orthogonal to the outer membrane. No major differences in the ET properties of MtrC and MtrF are found, implying that the different expression levels of the two proteins during extracellular respiration are not related to redox function.
Probing initial transient oligomerization events facilitating Huntingtin fibril nucleation at atomic resolution by relaxation-based NMR
Authors: Kotler Samuel A. , Tugarinov Vitali , Schmidt Thomas , Ceccon Alberto , Libich David S. , Ghirlando Rodolfo , Schwieters Charles D. , Clore G. Marius
Published: February 2019

The N-terminal region of the huntingtin protein, encoded by exon-1, comprises an amphiphilic domain (htt
NT
), a polyglutamine (Q

n

) tract, and a proline-rich sequence. Polyglutamine expansion results in an aggregation-prone protein responsible for Huntington’s disease. Here, we study the earliest events involved in oligomerization of a minimalistic construct, htt
NT
Q
7
, which remains largely monomeric over a sufficiently long period of time to permit detailed quantitative NMR analysis of the kinetics and structure of sparsely populated

(

≲
2%

)

oligomeric states, yet still eventually forms fibrils. Global fitting of concentration-dependent relaxation dispersion, transverse relaxation in the rotating frame, and exchange-induced chemical shift data reveals a bifurcated assembly mechanism in which the NMR observable monomeric species either self-associates to form a productive dimer (τ
ex
∼ 30 μs,
K
diss
∼ 0.1 M) that goes on to form a tetramer (

τ

ex

≲
25

μs;
K
diss
∼ 22 μM), or exchanges with a “nonproductive” dimer that does not oligomerize further (τ
ex
∼ 400 μs;
K
diss
∼ 0.3 M). The excited state backbone chemical shifts are indicative of a contiguous helix (residues 3–17) in the productive dimer/tetramer, with only partial helical character in the nonproductive dimer. A structural model of the productive dimer/tetramer was obtained by simulated annealing driven by intermolecular paramagnetic relaxation enhancement data. The tetramer comprises a
D
2
symmetric dimer of dimers with largely hydrophobic packing between the helical subunits. The structural model, validated by EPR distance measurements, illuminates the role of the htt
NT
domain in the earliest stages of prenucleation and oligomerization, before fibril formation.
Rhomboids make do with a weak hydrogen bond
Authors: Sedwick Caitlin
Published: February 2019

JGP paper explores the strength of the hydrogen bond network at the active site of GlpG.
Properly Diluted Fat (PDF): An Easy and Safe Approach to Periocular Fat Grafting
Authors: Pelle-Ceravolo Mario , Angelini Matteo
Published: February 2019

Background

The main challenge of periocular fat grafting is the risk of contour irregularities, especially in the lower eyelid. Injection of diluted fat can decrease the likelihood of poor contour.

Objectives

The authors developed a simple method of periocular fat grafting in which the fat was harvested through unconventional cannulas and diluted before the injection to avoid the risk of contour irregularities.

Methods

A retrospective study was conducted on 200 patients who underwent fat grafting to the periocular region. Lipoaspirate was obtained through a 0.5-mm multiple-hole cannula and then was centrifuged. A solution of 70% fat was prepared (ie, properly diluted fat [PDF]) with saline and infranatant fluid as the diluent. The recipient site was tunnelized with a 1.2-mm cannula, and PDF was transferred utilizing a 1.2-mm cannula containing a single 1-mm hole. Aesthetic improvement was ascertained from pre- and postoperative photographs evaluated by 3 examiners.

Results

A total of 164 (82%) patients received follow-up 6 months postoperatively, and 83 of these patients (41.5%) returned for monitoring 1 year postoperatively. Nearly all patients had improvement in periocular contour, but variable loss of volume was observed by 1 year. Patients who presented initially with scleral show often had noticeable improvement. At 1 year, only 3 patients experienced contour irregularities comprising soft bulges, similar to fat hernias. Two patients showed fat accumulation after substantial weight gain later than 1 year postoperatively.

Conclusions

Preparation and periocular delivery of PDF by the described techniques yield good contour with a low risk of visible masses occurrence.

Level of Evidence: 4
Gag-protease coevolution shapes the outcome of lopinavir-inclusive treatment regimens in chronically infected HIV-1 subtype C patients
Authors: Marie V , Gordon M
Published: February 2019

Motivation

Commonly, protease inhibitor failure is characterized by the development of multiple protease resistance mutations (PRMs). While the impact of PRMs on therapy failure are understood, the introduction of Gag mutations with protease remains largely unclear.

Results

Here, we utilized phylogenetic analyses and Bayesian network learning as tools to understand Gag-protease coevolution and elucidate the pathways leading to Lopinavir failure in HIV-1 subtype C infected patients. Our analyses indicate that while PRMs coevolve in response to drug selection pressure within protease, the Gag mutations added to the existing network while specifically interacting with known Lopinavir failure PRMs. Additionally, the selection of mutations at specific positions in Gag-protease suggests that these coevolving mutational changes occurs to maintain structural integrity during Gag cleavage.

Supplementary information

Supplementary data are available at Bioinformatics online.
Hearing Impairment and Cognitive Decline in Older, Community-Dwelling Adults
Authors: Alattar Ali A , Bergstrom Jaclyn , Laughlin Gail A , Kritz-Silverstein Donna , Richard Erin L , Reas Emilie T , Harris Jeffrey P , Barrett-Connor Elizabeth , McEvoy Linda K
Published: February 2019

Background

Hearing impairment is prevalent among older adults and has been identified as a risk factor for cognitive impairment and dementia. We evaluated the association of hearing impairment with long-term cognitive decline among community-dwelling older adults.

Methods

A population-based longitudinal study of adults not using hearing aids who had hearing acuity and cognitive function assessed in 1992–1996, and were followed for a maximum of 24 years with up to five additional cognitive assessments. Hearing acuity was categorized based on pure-tone average (PTA) thresholds: normal (PTA ≤ 25 dB), mild impairment (PTA > 25–40 dB), moderate/severe impairment (PTA > 40 dB).

Results

Of 1,164 participants (mean age 73.5 years, 64% women), 580 (49.8%) had mild hearing impairment and 196 (16.8%) had moderate/severe hearing impairment. In fully adjusted models, hearing impairment was associated with steeper decline on the Mini-Mental State Examination (MMSE) (mild impairment β = −0.04, p = .01; moderate/severe impairment β = −0.08, p = .002) and Trails B (mild impairment β = 1.21, p = .003; moderate/severe impairment β = 2.16, p = .003). Associations did not differ by sex or apolipoprotein E (APOE) ϵ4 status and were not influenced by social engagement. The MMSE-hearing association was modified by education: mild hearing impairment was associated with steeper decline on the MMSE among participants without college education but not among those with college education. Moderate/severe hearing impairment was associated with steeper MMSE decline regardless of education level.

Conclusions

Hearing impairment is associated with accelerated cognitive decline with age, and should be screened for routinely. Higher education may provide sufficient cognitive reserve to counter effects of mild, but not more severe, hearing impairment.
Prevalence of Human Immunodeficiency Virus-1 Integrase Strand Transfer Inhibitor Resistance in British Columbia, Canada Between 2009 and 2016: A Longitudinal Analysis
Authors: Kamelian Kimia , Lepik Katherine J , Chau William , Yip Benita , Zhang Wendy W , Lima Viviane Dias , Robbins Marjorie A , Woods Conan , Olmstead Andrea , Joy Jeffrey B , Barrios Rolando , Harrigan P Richard
Published: February 2019

Background

Integrase strand transfer inhibitors (INSTIs) are highly efficacious and well tolerated antiretrovirals with fewer adverse side-effects relative to other classes of antiretrovirals. The use of INSTIs raltegravir, elvitegravir, and dolutegravir has increased dramatically over recent years. However, there is limited information about the evolution and prevalence of INSTI resistance mutations in clinical human immunodeficiency virus populations.

Methods

Human immunodeficiency virus-1-positive individuals ≥19 years were included if they received ≥1 dispensed prescription of antiretroviral therapy (ART) in British Columbia between 2009 and 2016 (N = 9358). Physician-ordered drug resistance tests were analyzed and protease inhibitor (PI), reverse-transcriptase inhibitor (RT), and INSTI resistance were defined as having ≥1 sample with a combined, cumulative score ≥30 by Stanford HIV Drug Resistance Algorithm version 7.0.1.

Results

Although most ART-treated individuals were tested for PI and RT resistance, INSTI resistance testing lagged behind the uptake of INSTIs among INSTI-treated individuals (11% in 2009; 34% in 2016). The prevalence of INSTI resistance was relatively low, but it increased from 1 to 7 per 1000 ART-treated individuals between 2009 and 2016 (P < .0001, R2 = 0.98). Integrase strand transfer inhibitor resistance mutations increased at integrase codons 66, 97, 140, 148, 155, and 263.

Conclusions

The prevalence of INSTI resistance remains low compared with PI and RT resistance in ART-treated populations but is expanding with increased INSTI use.
Adverse Events During Treatment Induction With Injectable Diacetylmorphine and Hydromorphone for Opioid Use Disorder
Authors: Oviedo-Joekes Eugenia , Palis Heather , Guh Daphne , Marsh David C. , MacDonald Scott , Harrison Scott , Brissette Suzanne , Anis Aslam H. , Schechter Martin T.
Published: February 2019

Objectives:

The present study aims to describe a 3-day induction protocol for injectable hydromorphone (HDM) and diacetylmorphine (DAM) used in 3 Canadian studies and examine rates of opioid-related overdose and somnolence during this induction phase.

Methods:

The induction protocol and associated data on opioid-related overdose and somnolence are derived from 2 clinical trials and one cohort study conducted in Vancouver and Montreal (2005–2008; 2011–2014; 2014–2018). In this analysis, using the Medical Dictionary for Regulatory Activities coding system we report somnolence (ie, drowsiness, sleepiness, grogginess) and opioid overdose as adverse events. Overdoses requiring intervention with naloxone are coded as severe adverse events.

Results:

Data from the 3 studies provides a total of 1175 induction injections days, with 700 induction injection days for DAM, and 475 induction injection days for HDM. There were 34 related somnolence and adverse event (AE) overdoses (4.899 per 100 injection days) in DAM and 6 (1.467 per 100 days) in HDM. Four opioid overdoses requiring naloxone (0.571 per 100 injection days) were registered in DAM and 1 in HDM (0.211 per 100 injection days), all safely mitigated onsite. The first week maximum daily dose patients received were on average 433.62 mg [standard deviation (SD) = 137.92] and 223.26 mg (SD = 68.06) for DAM and HDM, respectively.

Conclusions:

A 3-day induction protocol allowed patients to safely reach high doses of injectable hydromorphone and diacetylmorphine in a timely manner. These findings suggest that safety is not an evidence-based barrier to the implementation of treatment with injectable hydromorphone and diacetylmorphine.
Implementation of the Alliance for Innovation on Maternal Health Program to Reduce Maternal Mortality in Malawi
Authors: Chang Olivia H. , Levy Barbara , Lytle Heather , Pope Rachel , Phiri Henry , Gellhaus Thomas , Eckhardt Carla , Sclafani Joseph
Published: February 2019

OBJECTIVE:

To evaluate maternal mortality and changes in the culture of safety before and after the implementation of the Alliance for Innovation on Maternal Health (AIM) Malawi program.

METHODS:

This was a prospective cohort study at a central hospital and a district health center in Malawi from March 2016 to November 2017. The AIM Malawi program included classroom didactics on obstetric hemorrhage, teamwork protocols, skills laboratory activities, and simulation training. The time periods of comparison were preintervention, education period, and postintervention. Hospital birth paper records were used to collect data on patient demographics and obstetric and neonatal information. The Hospital Survey of Patient Safety was used to measure the culture of safety before and after the program.

RESULTS:

We trained 128 participants. In the postintervention period, 16 procedural interventions were performed to manage postpartum hemorrhage, including B-lynch sutures (n=7), condom balloon catheter (n=5), nonpneumatic antishock garment (n=3), and uterine artery ligation (n=1). There was a significant increase in the use of B-lynch sutures for the management of uterine atony in the postintervention compared with preintervention period (P=.014). In the postintervention period, the rate of maternal mortality from obstetric hemorrhage decreased significantly from 1.2% to 0.2% (P=.02), a relative decrease of 82.1% from the preintervention rate. Hospital safety culture scores improved significantly from baseline in four out of five domains after the AIM Malawi training.

CONCLUSION:

After implementation of the AIM Malawi program, we found an increased use of postpartum hemorrhage procedural interventions, a decreased rate of maternal mortality and an increase in Hospital Survey of Patient Safety composite safety scores. The AIM Malawi program may be an effective framework for adaptation to improve maternal mortality in a low-resource setting.
Induced Abortion Provision Among a National Sample of Obstetrician–Gynecologists
Authors: Grossman Daniel , Grindlay Kate , Altshuler Anna L. , Schulkin Jay
Published: February 2019

OBJECTIVE:

To estimate the proportion of obstetrician–gynecologists (ob-gyns) who provided induced abortion in the prior year, disaggregated by surgical and medication methods, and document barriers to provision of medication abortion.

METHODS:

In 2016–2017, we conducted a cross-sectional survey of a national sample of American College of Obstetricians and Gynecologists Fellows and Junior Fellows who were part of the Collaborative Ambulatory Research Network. We sent the survey by email, and mailed nonresponders paper surveys. We performed descriptive statistics, χ2 tests, and logistic regression analyses.

RESULTS:

Sixty-seven percent (655/980) of Collaborative Ambulatory Research Network members responded. Ninety-nine percent reported seeing patients of reproductive age, and 72% reported having a patient in the prior year who needed or wanted an abortion. Among those seeing patients of reproductive age, 23.8% (95% CI 20.5%–27.4%) reported performing an induced abortion in the prior year; 10.4% provided surgical and medication abortion, 9.4% surgical only, and 4.0% medication only. In multivariable analysis, physicians practicing in the Midwest (adjusted odds ratio [AOR] 0.31, 95% CI 0.16–0.60) or South (AOR 0.22, 95% CI 0.11–0.42) had lower odds of provision compared with those practicing in the Northeast, whereas those practicing in an urban inner city (AOR 2.71, 95% CI 1.31–5.60) or urban non–inner-city area (AOR 2.89, 95% CI 1.48–5.64 vs midsize towns, rural areas, or military settings) had higher odds of provision. The most common reasons for not providing medication abortion were personal beliefs (34%) and practice restrictions (19%). Among those not providing medication abortion, 28% said they would if they could write a prescription for mifepristone.

CONCLUSION:

Compared with the previous national survey in 2008–2009, abortion provision may be increasing among practicing ob-gyns, although important geographic disparities persist. Few provide medication abortion, but uptake might increase if mifepristone could be prescribed.
Delayed Diagnosis of Microperforate Hymen Leading to Urethral Dilation Secondary to Coital Activity
Authors: Underwood Porshia G. , Bauer Jessica , Huguelet Patricia , Alaniz Veronica I.
Published: February 2019

BACKGROUND:

Urethral coitus can occur with vaginal and hymenal anomalies and typically presents with incontinence, dyspareunia, and recurrent urinary infections. Penetration of the urethra occurs unknowingly, and delayed diagnosis permits ongoing urethral coitus and dilation.

CASE:

A 23-year-old woman presented to a specialty clinic for a possible vaginal anomaly after failed intrauterine device insertion owing to difficulty locating the cervix. She reported regular menses and satisfying intercourse. Clinical examination revealed a dilated urethra from presumed urethral intercourse and a microperforate hymen with a 1-mm opening.

CONCLUSION:

This case highlights the importance of taking a thorough sexual history paired with careful examination of the external genitalia to correctly identify and diagnose vaginal and hymenal anomalies and to prevent long-term complications.
Venous Thromboembolism Among Women Initiating Depot Medroxyprogesterone Acetate Immediately Postpartum
Authors: Tepper Naomi K. , Jeng Gary , Curtis Kathryn M. , Boutot Maegan E. , Boulet Sheree L. , Whiteman Maura K.
Published: February 2019

OBJECTIVE:

To estimate the absolute and relative risk of venous thromboembolism (VTE) among women who initiate depot medroxyprogesterone acetate (DMPA) immediately postpartum compared with those who do not initiate hormonal contraception.

METHODS:

The IBM MarketScan Commercial Claims and Encounters databases were used to identify delivery hospitalizations among women aged 15–44 years during 2005 through 2014. Diagnosis, procedure, and drug codes were used to identify contraception, VTE, and potential confounding chronic or pregnancy-related conditions. Women who initiated DMPA during days 0 through 7 postpartum were compared with women who did not initiate hormonal contraception during days 0 through 7 postpartum. Women were followed from date of delivery through 12 weeks postpartum for the occurrence of VTE, with censoring at hormonal contraception initiation or prescription, hysterectomy, sterilization, or inpatient death. The incidence rate of VTE and 95% CIs were calculated within each group and the incidence rate ratio was calculated comparing the two groups.

RESULTS:

The unadjusted VTE incidence rate through 12 weeks postpartum was 0.42/10,000 women-days in the immediate postpartum DMPA group (34 events among 11,159 women contributing 805,999 days of follow-up) and 0.15/10,000 women-days in the control group (3,107 events among 3,102,011 women contributing 206,180,811 days of follow-up). The incidence rate ratio for VTE was 2.87 (95% CI 2.05–4.03) among women in the immediate postpartum DMPA group compared with women in the control group, adjusting for age alone. After adjusting for age and pregnancy-related and chronic conditions, the adjusted incidence rate ratio for VTE was 1.94 (95% CI 1.38–2.72) among women in the immediate postpartum DMPA group compared with women in the control group.

CONCLUSION:

Initiation of DMPA immediately postpartum is associated with a low incidence but an increased relative risk of VTE compared with nonuse of hormonal contraception.
Low-Cost Instructional Apparatus to Improve Training for Cervical Cancer Screening and Prevention
Authors: Parra Sonia , Oden Maria ,   for the Rice360 Student Team,, Schmeler Kathleen , Richards-Kortum Rebecca
Published: February 2019

BACKGROUND:

Cervical cancer remains one of the leading causes of cancer for women in medically underserved areas. This is in part due to a lack of trained clinicians to provide the necessary diagnosis and treatment of precancerous lesions to prevent cervical cancer. Increasing medical provider knowledge and skills is important for the early detection and prevention of cervical precancer and cancer in medically underserved areas of the United States and globally.

METHOD:

LUCIA is a low-cost, universal cervical cancer instructional apparatus that can be used to teach and practice a variety of essential skills for cervical cancer screening, diagnosis, and treatment, including: visual inspection with acetic acid, Pap and human papillomavirus DNA specimen collection, colposcopy, endocervical curettage, cervical biopsy, cryotherapy, and loop electrosurgical excision procedure.

EXPERIENCE:

LUCIA was used to provide hands-on training in six courses held in Texas (n=3), El Salvador (n=1), and Mozambique, Africa (n=2). Standardized provider evaluations were administered at three of these courses and resulted in mean scores of 4.12/5 for usefulness, 4.46/5 for skill improvement, and 4.43/5 for ease of skill evaluation.

CONCLUSION:

LUCIA provides dynamic, real-time feedback that allows trainees to learn and practice important skills related to cervical cancer prevention while simulating a patient exam.
Oral Gonadotropin-Releasing Hormone Antagonist Relugolix Compared With Leuprorelin Injections for Uterine Leiomyomas
Authors: Osuga Yutaka , Enya Kazuaki , Kudou Kentarou , Tanimoto Masataka , Hoshiai Hiroshi
Published: February 2019

OBJECTIVE:

To investigate the noninferiority of relugolix compared with leuprorelin acetate in reducing heavy menstrual bleeding associated with uterine leiomyomas.

METHODS:

In a double-blind, double-dummy trial, premenopausal women with uterine leiomyomas and heavy menstrual bleeding defined as a pictorial blood loss assessment chart score of at least 120 were randomized in a 1:1 ratio to relugolix (40 mg, oral, once daily) or leuprorelin acetate (1.88 mg or 3.75 mg, monthly injection) for 24 weeks. The primary endpoint was the proportion of patients with a total pictorial blood loss assessment chart score of less than 10 for weeks 6–12. Secondary endpoints included myoma and uterine volumes, and hemoglobin levels. A sample size of 144 patients per group (n=288) was estimated to provide at least 90% power to demonstrate noninferiority (prespecified noninferiority margin −15%; one-sided 0.025 level of significance).

RESULTS:

From March 2016 to September 2017, 281 patients were randomized (relugolix, n=139, leuprorelin n=142). Demographic and baseline characteristics were well balanced; mean pictorial blood loss assessment chart score was 254.3 in the relugolix group and 263.7 in the leuprorelin group. The proportion of patients with total pictorial blood loss assessment chart score of less than 10 for weeks 6–12 was 82.2% in the relugolix group and 83.1% in the leuprorelin group, demonstrating noninferiority of relugolix compared with leuprorelin (relugolix−leuprorelin difference −0.9%; 95% CI: −10.10 to 8.35; prespecified noninferiority margin −15%; P=.001). Reductions in myoma and uterine volumes and increases in hemoglobin levels were comparable in the two groups. Relugolix was associated with an earlier effect on menstrual bleeding than leuprorelin (pictorial blood loss assessment chart score of less than 10, 64.2% vs 31.7% [relugolix−leuprorelin difference 32.5%; 95% CI: 20.95–44.13%] for weeks 2–6 and pictorial blood loss assessment chart score of 0, 52.6% vs 21.8% [30.7%; 95% CI: 19.45–42.00%] for weeks 2–6) and faster recovery of menses after treatment discontinuation (relugolix median [Q1, Q3], 37 days [32.0, 46.0]; leuprorelin median, 65 days [54.0, 77.0]). Adverse events and bone mineral density loss were similar between relugolix and leuprorelin treatment groups.

CONCLUSION:

In women with uterine leiomyomas, once-daily treatment with relugolix, an oral gonadotropin-releasing hormone antagonist, demonstrated noninferiority to monthly leuprorelin for improvement of heavy menstrual bleeding at 6–12 weeks of treatment, had a more rapid effect on menstrual bleeding, and was generally well tolerated.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02655237; JAPIC Clinical Trial Information, JapicCTI-163128.

FUNDING SOURCE:

Takeda Pharmaceutical Company Limited and an affiliate of NovaQuest Capital Management LLC.
What Is New in Venous Thromboembolism Prophylaxis in Gynecologic Surgery?
Authors: Guntupalli Saketh R.
Published: February 2019

This month we will review the latest data on prevention of incidence of venous thromboembolism (VTE), which includes both deep venous thrombosis and pulmonary embolism, in patients undergoing gynecologic surgery. Dr. Guntupalli discusses four recent publications, which are concluded with a “bottom-line” that is the take-home message. A complete reference for each can be found on Box 1 on this page along with direct links to abstracts.
Propensity Score Adjusted Comparison of Pelviperineal Morbidity With and Without Omentoplasty Following Abdominoperineal Resection for Primary Rectal Cancer
Authors: Blok Robin D. , de Jonge Joske , de Koning Marlou A. , van de Ven Anthony W.H. , van der Bilt Jarmila D.W. , van Geloven Anna A.W. , Hompes Roel , Bemelman Wilhelmus A. , Tanis Pieter J.
Published: February 2019

BACKGROUND:

Abdominoperineal resection is associated with a high incidence of perineal complications, and whether this is reduced by an omentoplasty is still unclear.

OBJECTIVE:

This study aimed to investigate the impact of omentoplasty on pelviperineal morbidity in patients undergoing abdominoperineal resection for rectal cancer.

DESIGN:

This was a retrospective comparative cohort study using propensity score analyses to reduce potential confounding.

SETTING:

The study was undertaken in 2 teaching hospitals and 1 university hospital.

PATIENTS:

Patients who underwent abdominoperineal resection for primary rectal cancer between 2000 and 2017 were included.

MAIN OUTCOME MEASURES:

The main end points were primary perineal wound healing at 30 days and overall and specific pelviperineal morbidity until the end of the study period.

RESULTS:

Among 254 included patients, 106 had an omentoplasty. The primary perineal wound healing rate at 30 days was similar for omentoplasty and no omentoplasty (65% vs 60%; p = 0.422), also after adjusting for potential confounding by propensity score analysis (OR, 0.89; 95% CI, 0.45–1.75). Being free from any pelviperineal complication at 6 months (75% vs 79%; p = 0.492), absence of any pelviperineal morbidity until 1 year (54% vs 49%; p = 0.484), and incidence of persistent perineal sinus (6% vs 10%; p = 0.256) were also similar in both groups. The unadjusted higher perineal hernia rate after omentoplasty (18% vs 7%; p = 0.011) did not remain statistically significant after regression analysis including the propensity score (OR, 1.34; 95% CI, 0.46–3.88). Complications related to the omentoplasty itself were observed in 8 patients, of whom 6 required reoperation.

LIMITATIONS:

This study was limited by the retrospective and nonrandomized design causing some heterogeneity between the 2 cohorts.

CONCLUSION:

In this multicenter study using propensity score analyses, the use of omentoplasty did not lower the incidence or the duration of pelviperineal morbidity in patients undergoing abdominoperineal resection for rectal cancer, and omentoplasty itself was associated with a risk of reoperation. See Video Abstract at http://links.lww.com/DCR/A918.
Relationships of Statin Therapy and Hyperlipidemia With the Incidence, Rupture, Postrepair Mortality, and All-Cause Mortality of Abdominal Aortic Aneurysm and Cerebral Aneurysm: A Meta-analysis and Systematic Review
Authors: Cheng Wenke , Jia Xi , Li Jianting , Cheng Wensi , Liu Zhou , Lin Zongbin , Yang Chong
Published: February 2019

Statins have been suggested in previous studies to play a protective role in experimental cerebral aneurysm (CA) models; however, no evidence supports that the application of statins can protect against aneurysm rupture in humans, and the risks of lipid levels and aneurysms remain unknown. Therefore, this meta-analysis aimed to summarize and update the epidemiological evidence to systematically assess the relationships of statin therapy and hyperlipidemia with the incidence, rupture, postrepair mortality, and all-cause mortality of abdominal aortic aneurysm (AAA) and CA. Related studies were initially retrieved from the electronic databases PubMed, Embase, and Cochrane Library from inception to August 4, 2018. Subsequently, 33 studies were enrolled into this meta-analysis, and the maximum adjusted risk ratios (RRs) as well as the corresponding 95% confidence intervals were extracted. Finally, a total of 32 observational studies involving 150,134 participants were enrolled into this meta-analysis. The RRs of statin therapy for AAA incidence, AAA rupture, CA rupture, postrepair mortality, all-cause mortality, and adverse events were 1.83 (0.56–5.98), 0.67 (0.47–0.97), 0.50 (0.18–1.36), 0.60 (0.48–0.74), 0.66 (0.58–0.75), and 0.58 (0.47–0.71), respectively. Besides, the RR of hyperlipidemia for CA rupture was 0.79 (0.67–0.93). Our findings suggested that statin therapy could reduce the risks of AAA rupture, postrepair mortality, all-cause mortality, and adverse events, without inducing the risk of AAA incidence or CA rupture, and that hyperlipidemia was associated with a lower risk of CA rupture.
Prognostic Impact of Angiotensin-Converting Enzyme Inhibitors and Receptor Blockers on Recurrent Ventricular Tachyarrhythmias and Implantable Cardioverter–Defibrillator Therapies
Authors: Schupp Tobias , Behnes Michael , Weiß Christel , Nienaber Christoph , Lang Siegfried , Reiser Linda , Bollow Armin , Taton Gabriel , Reichelt Thomas , Ellguth Dominik , Engelke Niko , Bertsch Thomas , Akin Muharrem , Mashayekhi Kambis , Borggrefe Martin , Akin Ibrahim
Published: February 2019

This study sought to assess the prognostic impact of treatment with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) on recurrences of ventricular tachyarrhythmias in recipients of implantable cardioverter–defibrillators (ICD). Using a large retrospective registry including consecutive ICD recipients with documented episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2016, those patients treated with ACEi/ARB were compared with patients without. The primary prognostic endpoint was the first recurrence of ventricular tachyarrhythmias and related ICD therapies at 5 years. Multivariable Cox regression analyses were applied within the entire cohort, and thereafter, Kaplan–Meier analyses were performed in propensity-matched subgroups. A total of 592 consecutive ICD recipients were included (81% treated with ACEi/ARB and 19% without). Although ACEi/ARB was associated with no differences in overall recurrence of ventricular tachyarrhythmias, ACEi/ARB was associated with improved freedom from appropriate ICD therapy within multivariable Cox regressions (hazard ratio = 0.666; P = 0.043), especially in patients with index episodes of VF, left ventricular ejection fraction <35%, coronary artery disease, secondary preventive ICD, and glomerular filtration rate <45 mL/min/1.73 m2. In the propensity-matched subgroup, ACEi/ARB still prolonged freedom from appropriate ICD therapies (hazard ratio = 0.380; 95% confidence interval 0.193–0.747; P = 0.005). In conclusion, ACEi/ARB therapy was associated with improved freedom from appropriate ICD therapies.
Use of the Distal Facial Artery (Angular Artery) for Supermicrosurgical Midface Reconstruction
Authors: Yoshimatsu Hidehiko , Harima Mitsunobu , Iida Takuya , Narushima Mitsunaga , Karakawa Ryo , Nakatsukasa Shuichi , Yamamoto Takumi , Hayashi Akitatsu
Published: February 2019

Background:

In free-flap reconstruction of the midface, options for the recipient artery are quite limited; the superficial temporal artery and the facial artery are the most commonly used arteries. We report our approach for the use of the angular artery (the terminal branch of the facial artery) as the recipient artery in free-flap reconstruction of the midface.

Methods:

Nine patients with midface defects underwent free-flap reconstructions using the angular artery as the recipient artery. Identification and marking of the facial artery were performed preoperatively using handheld Doppler ultrasound. The angular artery was located through an incision made on the side of the nose. When present, a vena comitans of the facial artery or any subcutaneous vein in the vicinity of the defect was used as the recipient vein. In other cases, the facial vein in the submandibular region was chosen as the recipient vein, using a vein graft.

Results:

The average diameter of the angular artery was 0.9 mm (range, 0.7–1.0 mm). In all cases, arterial anastomosis was performed in an end-to-end fashion, and flaps survived completely. In 4 cases, a vein graft was used to bridge the pedicle vein and the facial vein.

Conclusions:

Although supermicrosurgical skills may be required for its anastomosis, the angular artery is an anatomically consistent artery, which is suitable for use as the recipient artery in free-flap reconstruction of the midface. Use of the angular artery as the recipient artery allows shorter flap pedicles and decreases the number of vein grafts necessary.
Cutaneous Myxoma of Multiple Lesions
Authors: Iida Ken , Egi Takeshi , Shigi Masato , Sogabe Yusuke , Ohashi Hirotsugu
Published: February 2019

Cutaneous myxoma is a rare neoplasm typically occurring as an asymptomatic nodule on the head, neck, and chest regions of adults. However, multiple cutaneous myxoma of the subungual space is even rarer. Here, we report a case of multiple cutaneous myxoma of the subungual space in which the tumor was removed by creating a mid-radial incision while preserving the nail matrix. The excisional biopsy samples were dispatched for histopathological examination and confirmed to be cutaneous myxoma. To the best of our knowledge, this is the first report on multiple cutaneous myxoma of the subungual space.