bluuebunny/crossref_metadata_2025 huggingface dataset:
Agglutination of plasma, hemocyanin, and separated hemocyanin from the hemolymph of the freshwater prawn Macrobrachium rosenbergii (De Man, 1879) (Decapoda: Caridea: Palaemonidae)
Authors: Sivakumar Mullaivanam R , Denis Maghil , Sivakumar Shanthi , Arumugam Munusamy
Published: March 2020

Hemocyanin, the predominant protein in the hemolymph of crustaceans, was isolated from the plasma of the giant freshwater prawn Macrobrachium rosenbergii (De Man, 1879) and investigated, with its separated proteins MrHc1, 2, 3, and 4 (60, 114, 50, and 325 kDa, respectively) for hemagglutination (HA) activity. Hemocyanin against erythrocytes from human A, B, and O blood groups, mouse, rat sheep, water buffalo, and rabbit showed HA titer values higher than plasma. Of the four proteins isolated from hemocyanin, MrHc1 alone appeared to agglutinate the tested erythrocytes. Evaluated specific hemagglutination activity was higher for hemocyanin when compared to plasma. Sugar binding ability with N-acetylated sugars observed for plasma was restricted to N-acetyl neuraminic acid for hemocyanin and MrHc1. Inhibition of hemagglutination (HAI) by bovine submaxillary mucin (BSM) further defined the agglutination ability of hemocyanin and MrHc1. The hemocyanin protein MrHc1 on matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI–TOF/MS) and search in MASCOT database showed homology to hypothetical protein of Branchiostoma floridae Hubbs, 1922 (Cephalochordata). The results clearly indicated that the structure of the hemocyanin had evolved binding sites for sugar or sugar-linkages independently lacking homology with other hemocyanin or lectin-like proteins. The immunogenicity of this hemocyanin probably has biomedical applications as carrier adjuvants, which needs further investigation.
Accumulation of Astrocytic Aquaporin 4 and Aquaporin 1 in Prion Protein Plaques
Authors: Sadashima Shoko , Honda Hiroyuki , Suzuki Satoshi O , Shijo Masahiro , Aishima Shinichi , Kai Keita , Kira Junichi , Iwaki Toru
Published: March 2020

Gerstmann-Sträussler-Scheinker (GSS) disease with P102L mutation and familial Creutzfeldt-Jakob disease (CJD) with V180I mutation are 2 major hereditary prion diseases in Japan. GSS and some familial CJD [V180I] exhibit characteristic prion protein (PrP) plaques. Overexpression of the astrocytic water channel proteins aquaporin (AQP) 1 and AQP4 was recently reported in sporadic CJD. To clarify the pathological characteristics of AQP1 and AQP4 in prion disease patient brains with plaque-type deposition, we investigated 5 patients with GSS, 2 patients with CJD [V180I], and 2 age-matched control cases without neurological diseases using immunohistochemistry and double immunofluorescence methods. We demonstrated that there is the intense expression of AQP1 and AQP4 around prion plaques, especially in distal astrocytic processes deep inside these plaques. Similar results have been reported in the senile plaques and ghost tangles of Alzheimer disease brains and a protective role of AQP4 in which AQP4 is redistributed toward the plaques and works as a barrier against the deleterious effects of these plaques has been suggested. Our results, which show a similar clustering of AQPs around PrP plaques, therefore support the possibility that AQPs also have a protective role in plaque formation in prion diseases.
What Every Neuropathologist Needs to Know: Peripheral Nerve Biopsy
Authors: Chkheidze Rati , Pytel Peter
Published: March 2020

Peripheral neuropathy is a common disorder with many possible etiologies including metabolic diseases, inflammatory conditions, infections, malignancy, inherited diseases, drugs, and toxins. In most instances, diagnosis and treatment plan can be established based on clinical presentation, family history, laboratory results, genetic testing, and electrophysiological studies. But in some situations, a peripheral nerve biopsy remains a valuable tool. This is especially true in patients with rapidly progressive disease, with atypical presentation or for whom other approaches fail to yield a definitive diagnosis. The pathologic examination starts with basic decisions about specimen triage. A few basic questions help to provide an initial framework for the assessment of a nerve biopsy—is the specimen adequate; are there inflammatory changes; are there vascular changes; is there amyloid; are there changes to axonal density and the Schwann cell-myelin-axon unit. In the appropriate context and with such an approach peripheral nerve biopsies can still represent a clinically helpful test.
The Milky Way’s stellar streams and globular clusters do not align in a Vast Polar Structure
Authors: Riley Alexander H , Strigari Louis E
Published: March 2020

There is increasing evidence that a substantial fraction of Milky Way satellite galaxies align in a rotationally supported plane of satellites, a rare configuration in cosmological simulations of galaxy formation. It has been suggested that other Milky Way substructures (namely young halo globular clusters and stellar/gaseous streams) similarly tend to align with this plane, accordingly dubbed the Vast Polar Structure (VPOS). Using systemic proper motions inferred from Gaia data, we find that globular cluster orbital poles are not clustered in the VPOS direction, though the population with the highest VPOS membership fraction is the young halo clusters (∼30 per cent). We additionally provide a current census of stellar streams, including new streams discovered using the Dark Energy Survey and Gaia data sets, and find that stellar stream normals are also not clustered in the direction of the VPOS normal. We also find that, based on orbit modelling, there is a likely association between NGC 3201 and the Gjöll stellar stream and that, based on its orbital pole, NGC 4147 is likely not a Sagittarius globular cluster. That the Milky Way’s accreted globular clusters and streams do not align in the same planar configuration as its satellites suggests that the plane of satellites is either a particularly stable orbital configuration or a population of recently accreted satellites. Neither of these explanations is particularly likely in light of other recent studies, leaving the plane of satellites problem as one of the more consequential open problems in galaxy formation and cosmology.
Effect of sphingosine-1-phosphate on activation of dormant follicles in murine and human ovarian tissue
Authors: Pors Susanne Elisabeth , Harðardóttir Lilja , Olesen Hanna Ørnes , Riis Malene Lundgaard , Jensen Lea Bejstrup , Andersen Astrid Sten , Cadenas Jesús , Grønning Annika Patricia , Colmorn Lotte Berdiin , Dueholm Margit , Andersen Claus Yding , Kristensen Stine Gry
Published: March 2020

In vitro activation of resting ovarian follicles, with the use of mechanical stress and/or pharmacological compounds, is an emerging and novel approach for infertility treatment. The aim of this study was to assess the sphingolipid, sphingosine-1-phosphate (S1P), as a potential in vitro activation agent in murine and human ovarian tissues and isolated follicles. Juvenile murine ovaries and donated human ovarian tissues, from 10 women undergoing ovarian tissue cryopreservation for fertility preservation, were incubated with or without 12 μM S1P for 3 h for quantitative PCR analysis, and 12 h for xenotransplantation or culture studies. Gene expression analyses were performed for genes downstream of the Hippo signaling pathway. Murine ovaries and isolated murine and human preantral follicles showed significantly increased mRNA expression levels of Ccn2/CCN2 following S1P treatment compared to controls. This increase was shown to be specific for the Hippo signaling pathway and for the S1P2 receptor, as co-treatment with Hippo-inhibitor, verteporfin and S1PR2 antagonist, JTE-013, reduced the S1P-induced Ccn2 gene expression in murine ovaries. Histological evaluation of human cortical tissues (5 × 5 × 1 mm; n = 30; three pieces per patient) xenografted for 6 weeks and juvenile murine ovaries cultured for 4 days (n = 9) or allografted for 2 weeks (n = 48) showed no differences in the distribution of resting or growing follicles in S1P-treated ovarian tissues compared to controls. Collectively, S1P increased Ccn2/CCN2 gene expression in isolated preantral follicles and ovarian tissue from mice and human, but it did not promote follicle activation or growth in vivo. Thus, S1P does not appear to be a potent in vitro activation agent under these experimental conditions.
Midthoracic Punctate Midline Myelotomy for Treatment of Chronic, Intractable, Nonmalignant, Abdominal Visceral Pain: 2-Dimensional Operative Video
Authors: Ball Tyler , Aljuboori Zaid , Nauta Haring
Published: March 2020

Punctate midline myelotomy (PMM) is a surgical procedure that damages the ascending fibers of the postsynaptic dorsal column (PSDC) pathway to interrupt visceral pain transmission.
1-3
It can offer relief to patients with chronic visceral pain conditions that are refractory to other treatments. Here, we present a surgical video of midthoracic PMM in a patient with chronic, intractable, nonmalignant visceral abdominal pain that failed over a decade of medical treatment. We choose T7-8 as the level for laminectomy in patients with pelvic or lower abdominal pain, because the postsynaptic pain fibers transmitting visceral pain sensation from the lower abdominal organs will invariably be caudal to this level. The patient developed immediate and complete relief of her visceral pain after the procedure, which was sustained through the 11-wk follow-up period to date and was able to be weaned off narcotics. Postoperatively, she remained full strength and had no impairment of light touch or proprioception of her lower extremities. Detailed physical examination showed a reduced vibratory sensation on the glabrous skin of her great toes. Regarding patient-reported sensory changes (not detected on physical examination), she reported some numbness on the insides of her feet that had resolved by 11-wk follow-up. She also reported some numbness of the vulva, but not of the vagina. However, by 11-wk follow-up, she reported this had resolved and she had normal sexual function. The only persistent sensation at 11-wk follow-up was slight tingling in her toes that was not bothersome to her.
4
The patient presented in the following video consented to both the surgical procedure and the publication of her clinical history and operative video.
Nutritional evaluation of the neurologically impaired child
Authors: Casey Linda M
Published: March 2020

Nutrition is of key importance in optimizing function and health in children with neurological impairment. Challenges in quantifying individual needs and assessing nutritional status are barriers to determining the nutritional prescription. This practice point addresses common questions faced by clinicians caring for this population and uses available evidence to provide strategies to address these challenges.
L’évaluation nutritionnelle de l’enfant présentant une déficience neurologique
Authors: Casey Linda M
Published: March 2020

La nutrition est capitale pour optimiser l’activité fonctionnelle et la santé des enfants présentant une déficience neurologique. Les difficultés éprouvées pour quantifier les besoins individuels et évaluer l’état nutritionnel de ces enfants représentent des obstacles à l’établissement de prescriptions nutritionnelles. Le présent point de pratique répond à des questions fréquentes avec lesquelles les cliniciens qui soignent cette population sont aux prises et puise dans les données probantes afin de proposer des stratégies pour venir à bout de ces difficultés.
Gut epithelial impairment, microbial translocation and immune system activation in inflammatory bowel disease–associated spondyloarthritis
Authors: Luchetti Michele Maria , Ciccia Francesco , Avellini Chiara , Benfaremo Devis , Rizzo Aroldo , Spadoni Tatiana , Svegliati Silvia , Marzioni Daniela , Santinelli Alfredo , Costantini Andrea , Viola Nadia , Berretta Antonella , Ciferri Monia , Mattioli Belmonte Cima Monica , Mosca Piergiorgio , Benedetti Antonio , Gabrielli Armando
Published: March 2020

Objectives

Gut microbiota has been widely reported to be involved in systemic inflammation through microbial translocation and T cell activation in several diseases. In this work we aimed to investigate bacterial infiltration and epithelial impairment in the gut of patients with IBD-associated SpA (SpA-IBD), as well as the relationship of microbial translocation with immune system activation and their putative role in the pathogenesis of joint inflammation in IBD patients.

Methods

Tight-junction proteins (TJPs) occludin and claudin-1/-4 and bacteria were assessed by real-time PCR analysis and immunohistochemical staining of the ileum. Intestinal fatty acid binding protein (I-FABP), lipopolysaccharides (LPS), soluble CD14 (sCD14), sclerostin and anti-sclerostin antibodies (anti-sclerostin-IgG) were assayed with ELISAs and peripheral mononuclear blood cells with flow cytometry. LPS and sCD14 were used in vitro to stimulate a human osteoblast cell line.

Results

Compared with IBD, ileal samples from SpA-IBD patients showed bacterial infiltration, epithelial damage and downregulation of TJPs. In sera, they showed higher serum levels of I-FABP, LPS, sCD14 (the latter correlating with sclerostin and anti-sclerostin-IgG) and higher CD80+/CD163+ and lower CD14+ mononuclear cells. In vitro experiments demonstrated that only the LPS and sCD14 synergic action downregulates sclerostin expression in osteoblast cells.

Conclusion

SpA-IBD patients are characterized by gut epithelium impairment with consequent translocation of microbial products into the bloodstream, immune system activation and an increase of specific soluble biomarkers. These findings suggest that gut dysbiosis could be involved in the pathogenesis of SpA-IBD and it could hopefully prompt the use of these biomarkers in the follow-up and management of IBD patients.
Quantification of Cadophora luteo-olivacea From Grapevine Nursery Stock and Vineyard Soil Using Droplet Digital PCR
Authors: Maldonado-González María Mercedes , del Pilar Martínez-Diz María , Andrés-Sodupe Marcos , Bujanda Rebeca , Díaz-Losada Emilia , Gramaje David
Published: March 2020

Cadophora luteo-olivacea is the most prevalent Cadophora species associated with Petri disease and esca of grapevine. Accurate, early, and specific detection and quantification of C. luteo-olivacea are essential to alert growers and nurseries to the presence of the pathogens in soil and to prevent the spread of this pathogen through grapevine planting material. The aim of this study was to develop molecular tools to detect and quantify C. luteo-olivacea inoculum from environmental samples. Species specific primers based on the β-tubulin gene and a TaqMan probe for droplet digital PCR (ddPCR) and quantitative PCR (qPCR) were first developed to detect and quantify purified DNA of the target fungus. Specificity tests showed that the primers were able to amplify the C. luteo-olivacea DNA (20 isolates) while none of the 29 nontarget fungal species (58 isolates) tested were amplified. The ddPCR was shown to be more sensitive compared with qPCR in the detection and quantification of C. luteo-olivacea at very low concentrations and was further selected to accurately detect and quantify the fungus from environmental samples. Twenty-five of the 94 grafting plants (26.6%) analyzed by ddPCR tested positive to C. luteo-olivacea DNA (>3 copies/µl). C. luteo-olivacea was barely detected from vineyard soils. The procedure employed in this study revealed the presence of the pathogen in symptomless vines, which makes implementation of this technique suitable for certification schemes of C. luteo-olivacea-free grapevine planting material.
Characterization, Phylogeny, and Genome Analyses of Nonpathogenic Xanthomonas campestris Strains Isolated from Brassica Seeds
Authors: Lee Yung-An , Yang Pei-Yu , Huang Shau-Chang
Published: March 2020

Xanthomonads were detected by using the Xan-D(CCF) medium from the brassica seeds, and their pathogenicity was determined by plant inoculation tests. It was found that some seed lots were infested with Xanthomonas campestris pv. campestris, some with X. campestris pv. raphani, and some with nonpathogenic xanthomonads. The nonpathogenic xanthomonad strains were identified as X. campestris, and the multilocus sequence analysis showed that the nonpathogenic X. campestris strains were grouped together with pathogenic X. campestris, but not with nonpathogenic strains of X. arboricola. In addition, all isolated X. campestris pv. campestris and X. campestris pv. raphani strains were positive in the hrpF-PCR, but the nonpathogenic strains were negative. It was further found that nonpathogenic X. campestris strain nE1 does not contain the entire pathogenicity island (hrp gene cluster; type III secretion system) and all type III effector protein genes based on the whole genome sequence analyses. The nonpathogenic X. campestris strain nE1 could acquire the entire pathogenicity island from the endemic X. campestris pv. campestris and X. campestris pv. raphani strains by conjugation, but type III effector genes were not cotransferred. The studies showed that the nonpathogenic X. campestris strains indeed exist on the brassica seeds, but it could be differentiated by the PCR assays on the hrp and type III effector genes. Nevertheless, the nonpathogenic X. campestris strains cannot be ignored because they may be potential gene resources to increase genetic diversity in the endemic pathogenic X. campestris pv. campestris and X. campestris pv. raphani strains.
Imaging Pseudotumors of the Shoulder
Authors: Bernot Jeremy M. , Byerly Douglas W. , Bui-Mansfield Liem T.
Published: March 2020

Normal variants and benign pseudotumors are common findings on imaging throughout the body. Pseudotumors of the shoulder are common discoveries on routine and emergent shoulder imaging examinations that can create diagnostic conundrums for the radiologist (Table 1). As the volume of medical imaging continues to increase, knowledge of these findings will be essential for accurate diagnosis. Misdiagnosis of a pseudotumor may lead to patient anxiety, unnecessary procedures, surgery, or other medical treatment.
Preparing for the MD: How Long, at What Cost, and With What Outcomes?
Authors: Gonnella Joseph S. , Callahan Clara A. , Erdmann James B. , Veloski J. Jon , Jafari Niusha , Markle Ronald A. , Hojat Mohammadreza
Published: March 2020

Purpose

To assess educational and professional outcomes of an accelerated combined bachelor of science–doctor of medicine (BS–MD) program using data collected from 1968 through 2018.

Method

Participants of this longitudinal study included 2,235 students who entered medical school between 1968 and 2014: 1,134 in the accelerated program and 1,101 in the regular curriculum (control group)—matched by year of entrance to medical school, gender, and Medical College Admission Test (MCAT) scores. Outcome measures included performance on medical licensing examinations, academic progress, satisfaction with medical school, educational debt, first-year residency program directors’ ratings on clinical competence, specialty choice, board certification, and faculty appointments.

Results

The authors found no practically important differences between students in the accelerated program and those in the control group on licensing examination performance, academic progress, specialty choice, board certification, and faculty appointments. Accelerated students had lower mean educational debt (P < .01, effect sizes = 0.81 and 0.45 for, respectively, their baccalaureate debt and medical school debt), lower satisfaction with their second year of medical school (P < .01, effect size = 0.21), and lower global satisfaction with their medical school education (P < .01, effect size = 0.35). Residency program directors’ ratings in 6 postgraduate competency areas showed no practically important differences between the students in the accelerated program and those in the control group. The proportion of Asian students was higher among program participants (P < .01, effect size = 0.43).

Conclusions

Students in the accelerated program earned BS and MD degrees at a faster pace and pursued careers that were comparable to students in a matched control who were in a regular MD program. Findings indicate that shortening the length of medical education does not compromise educational and professional outcomes.
The Urgent Need for Hepatitis C Screening in Pregnant Women
Authors: Saab Sammy , Kullar Ravina , Gounder Prabhu
Published: March 2020

Hepatitis C virus (HCV) infection affects 170 million people worldwide, with at least 5% of individuals with HCV progressing to life-threatening complications, including hepatocellular carcinoma, within 20 years from acute infection. The World Health Organization has called for viral hepatitis elimination as a major public health threat by 2030. The recent development and availability of direct-acting antiviral drugs have been a game-changer in the HCV-treatment paradigm—response exceeds 90%, with minimal adverse events. Accordingly, the U.S. Preventive Services Task Force and the American Association for the Study of Liver Disease–Infectious Diseases Society of America 2019 guidelines recommend universal HCV screening for all adults aged 18–79 years, including pregnant women. Worldwide, up to 8% of pregnant women have HCV infection, with the prevalence being as high as 4% in the United States. Pregnancy is one of the few points of contact women of reproductive age have with their health care providers; therefore, pregnancy provides a crucial time for targeting this population for HCV screening. Children also benefit from maternal screening, because the primary route of infection in children is vertical transmission during pregnancy, and children are not routinely assessed for liver disease. In fact, 85–95% of children with HCV infection in the United States are not yet identified with current strategies. In this commentary, we highlight why universal screening in pregnant women should be recommended by the American College of Obstetricians and Gynecologists based on the current epidemiology of HCV and the upcoming U.S. Preventive Services Task Force–recommended screening changes for all adults aged 18–79 years. We also review the current screening paradigm and treatment options for pregnant women and their children.
Effect of Thyroxine Therapy on Depressive Symptoms Among Women With Subclinical Hypothyroidism
Authors: Costantine Maged M. , Smith Karen , Thom Elizabeth A. , Casey Brian M. , Peaceman Alan M. , Varner Michael W. , Sorokin Yoram , Reddy Uma M. , Wapner Ronald J. , Boggess Kim , Tita Alan T.N. , Rouse Dwight J. , Sibai Baha , Iams Jay D. , Mercer Brian M. , Tolosa Jorge E. , Caritis Steve N. , VanDorsten J. Peter ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network, Bethesda, MD
Published: March 2020

OBJECTIVE:

To estimate the effect of antenatal treatment of subclinical hypothyroidism on maternal depressive symptoms.

METHODS:

We conducted an ancillary study to a multicenter trial in women with singleton pregnancies diagnosed with subclinical hypothyroidism randomized to antenatal thyroxine therapy or placebo. Treatment was discontinued at the end of pregnancy. Women with overt thyroid disease, diabetes, autoimmune disease, and those diagnosed with depression were excluded. Participants were assessed for depressive symptoms using the Center for Epidemiological Studies-Depression scale (CES-D) before starting the study drug (between 11 and 20 weeks of gestation), between 32 and 38 weeks of gestation, and at 1 year postpartum. The primary outcome was maternal depressive symptoms score as assessed using the CES-D. Secondary outcome was the percentage of women who scored 16 or higher on the CES-D, as such a score is considered screen-positive for depression.

RESULTS:

Two hundred forty-five (36.2% of parent trial) women with subclinical hypothyroidism were allocated to thyroxine (n=124) or placebo (n=121). Median CES-D scores and the proportion of participants with positive scores were similar at baseline between the two groups. Treatment with thyroxine was not associated with differences in CES-D scores (10 [5–15] vs 10 [5–17]; P=.46) or in odds of screening positive in the third trimester compared with placebo, even after adjusting for baseline scores (24.3% vs 30.1%, adjusted odds ratio 0.63, 95% CI 0.31–1.28, P=.20). At 1 year postpartum, CES-D scores were not different (6 [3–11] vs 6 [3–12]; P=.79), nor was the frequency of screen-positive CES-D scores in the treated compared with the placebo group (9.7% vs 15.8%; P=.19). Treatment with thyroxine during pregnancy was also not associated with differences in odds of screening positive at the postpartum visit compared with placebo even after adjusting for baseline scores. Sensitivity analysis including women who were diagnosed with depression by the postpartum visit did not change the results.

CONCLUSIONS:

This study did not achieve its planned sample size, thus our conclusions may be limited, but in this cohort of pregnant women with subclinical hypothyroidism, antenatal thyroxine replacement did not improve maternal depressive symptoms.
Psychosocial Factors Associated With Postpartum Contraceptive Method Use After an Unintended Birth
Authors: Steinberg Julia R. , Harrison Eowna Young , Boudreaux Michel
Published: March 2020

OBJECTIVE:

To examine whether depression, intimate partner violence, and other psychosocial stressors were independently associated with effectiveness level of postpartum contraception among women who recently had an unintended birth.

METHODS:

We analyzed cross-sectional data from PRAMS (the Pregnancy Risk Assessment Monitoring System) to identify women who had an unintended birth between 2012 and 2015. The effectiveness level of the contraceptive method was coded into one of five categories based on the postpartum contraceptive method that women were using: none, less effective (withdrawal, rhythm, condoms, or other barrier), moderately effective (pill, patch, ring, or shot), long-acting reversible contraception (LARC; intrauterine devices or implants), and sterilization (female or male sterilization). Multinomial logistic regression was used to examine whether prepregnancy depression or elevated postpartum depressive symptoms, intimate partner violence before or during pregnancy, and number of psychosocial stressors before birth were associated with effectiveness level of method (compared with no method), in models adjusted for sociodemographics, pregnancy context, and postpartum context.

RESULTS:

Complete data were available for 56,445 (88.2%) of the 64,030 eligible women: 24.2% experienced depression; 5.3% experienced intimate partner violence; and 16.8% experienced five or more psychosocial stressors around the time of pregnancy or birth. In adjusted models, experiencing intimate partner violence and more stressors lowered women's relative risk of using sterilization, LARC, moderately effective methods, and less-effective contraceptive methods relative to no method use. Only prepregnancy depression was associated with using sterilization compared with no method use.

CONCLUSIONS:

Experiencing intimate partner violence and having more psychosocial stressors were each independently associated with not using a postpartum contraceptive method. Standardized screening for psychosocial factors during prenatal and postpartum care should be integrated, and practices that encourage the discussion of patients' psychosocial experiences and postpartum contraception use together are warranted.
Hepatitis C Virus Antibody Screening in a Cohort of Pregnant Women
Authors: Prasad Mona , Saade George R. , Sandoval Grecio , Hughes Brenna L. , Reddy Uma M. , Mele Lisa , Salazar Ashley , Varner Michael W. , Gyamfi-Bannerman Cynthia , Thorp John M. , Tita Alan T. N. , Swamy Geeta K. , Chien Edward K. , Casey Brian M. , Peaceman Alan M. , El-Sayed Yasser Y. , Iams Jay D. , Gibbs Ronald S. , Sibai Baha , Wiese Nicholas , Kamili Saleem , Macones George A. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network
Published: March 2020

OBJECTIVE:

To describe the prevalence of hepatitis C virus (HCV) antibody, evaluate current risk factors associated with HCV antibody positivity, and identify novel composite risk factors for identification of groups most likely to demonstrate HCV antibody seropositivity in an obstetric population from 2012 to 2015.

METHODS:

The Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network initiated an observational study of mother-to-child transmission of HCV in 2012 that included offering HCV antibody screening to their entire obstetric population. Women presenting for prenatal care before 23 weeks of gestation without a known multifetal gestation were eligible. For each woman who was HCV antibody–positive, two women at similar gestational age who were HCV antibody–negative were identified and included for comparison. Risk factors were evaluated by patient interview and chart review. Women in the case group were identified to have a signal-to-cutoff value of at least 5 on the Abbott ARCHITECT platform. RNA status was evaluated for women in the case group.

RESULTS:

Of 106,842 women screened for the HCV antibody, 254 had positive results. The HCV antibody seroprevalence rate was 2.4 cases per 1,000 women (95% CI 2.1–2.7). One hundred thirty-one women in the case group and 251 women in the control group were included in the case–control analysis. Factors associated with HCV antibody positivity included injection drug use (adjusted odds ratio [aOR] 22.9, 95% CI 8.2–64.0), blood transfusion (aOR 3.7, 95% CI 1.3–10.4), having a partner with HCV (aOR 6.3, 95% CI 1.8–22.6), more than three lifetime sexual partners (aOR 5.3, 95% CI 1.4–19.8), and smoking (aOR 2.4, 95% CI 1.2–4.6). A composite of any of these potential risk factors provided the highest sensitivity for detecting HCV antibody (75/82 cases, 91%).

CONCLUSION:

In this cohort, the seroprevalence of HCV antibody was low, and the current risk factors for HCV screening were not identified. These findings may be useful in defining new strategies for identifying mothers with the HCV antibody and the neonates susceptible to maternal transmission of HCV.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT01959321.
Efficacy, Safety, and Tolerability of a New Low-Dose Copper and Nitinol Intrauterine Device
Authors: Turok David K. , Nelson Anita L. , Dart Clint , Schreiber Courtney A. , Peters Kevin , Schreifels Mary Jo , Katz Bob ,   on behalf of the VeraCept Phase 2 Clinical Investigator Group
Published: March 2020

OBJECTIVE:

To assess in parous and nulliparous women, the efficacy, safety, and tolerability of a new, low-dose copper (175 mm2) intrauterine contraceptive with a flexible nitinol frame provided in a preloaded applicator.

METHODS:

Institutional review boards at 12 U.S. sites approved this commercially funded project. Patients met standard inclusion and exclusion criteria for a copper-based intrauterine device (IUD), generally consistent with the Centers for Disease Control and Prevention's U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. Intrauterine device placement occurred at any day in the eligible patient's menstrual cycle after assuring she was not pregnant. The primary outcome measure assessed efficacy (measured by the Pearl Index) in this 1-year study with a 2-year extension. Secondary outcomes included placement success, ease of placement, safety as measured by adverse events, and tolerability assessed by discontinuation rate and bleeding and spotting patterns.

RESULTS:

A total of 286 women provided 5,640 cycles evaluable for pregnancy. Patients averaged 27.1 years of age. Nulliparous women represented 60.8% of the patients. Over 36 months of observation, we identified two pregnancies (Pearl Index 0.46 [95% CI 0.06–1.67]) and 10 serious adverse events; none were study-related. Successful placement occurred in 283 participants (99.0%). Median (range) continuation times were 2.7 years (0–3.4). We identified five expulsions (1.8%), zero uterine perforations, and one report of pelvic inflammatory disease. Adverse events prompted 30 women (10.6%) to discontinue early in the first year of use with 23 (8.1%) discontinuing for issues of bleeding, pain, or both. Altogether, 107 (37.8%) completed 36 months of device use. Mean bleeding days per cycle decreased from 7.6 in cycle 1 to 5.2 in cycle 13.

CONCLUSION:

The novel, low-dose copper and nitinol IUD demonstrated high efficacy and safety in this phase 2 U.S. Food and Drug Administration trial and warrants further expanded study in a phase 3 clinical trial.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02446821.

FUNDING SOURCE:

Sebela Pharmaceuticals, Inc.
Machine Learning and Statistical Models to Predict Postpartum Hemorrhage
Authors: Venkatesh Kartik K. , Strauss Robert A. , Grotegut Chad A. , Heine R. Philip , Chescheir Nancy C. , Stringer Jeffrey S. A. , Stamilio David M. , Menard Katherine M. , Jelovsek J. Eric
Published: March 2020

OBJECTIVE:

To predict a woman's risk of postpartum hemorrhage at labor admission using machine learning and statistical models.

METHODS:

Predictive models were constructed and compared using data from 10 of 12 sites in the U.S. Consortium for Safe Labor Study (2002–2008) that consistently reported estimated blood loss at delivery. The outcome was postpartum hemorrhage, defined as an estimated blood loss at least 1,000 mL. Fifty-five candidate risk factors routinely available on labor admission were considered. We used logistic regression with and without lasso regularization (lasso regression) as the two statistical models, and random forest and extreme gradient boosting as the two machine learning models to predict postpartum hemorrhage. Model performance was measured by C statistics (ie, concordance index), calibration, and decision curves. Models were constructed from the first phase (2002–2006) and externally validated (ie, temporally) in the second phase (2007–2008). Further validation was performed combining both temporal and site-specific validation.

RESULTS:

Of the 152,279 assessed births, 7,279 (4.8%, 95% CI 4.7–4.9) had postpartum hemorrhage. All models had good-to-excellent discrimination. The extreme gradient boosting model had the best discriminative ability to predict postpartum hemorrhage (C statistic: 0.93; 95% CI 0.92–0.93), followed by random forest (C statistic: 0.92; 95% CI 0.91–0.92). The lasso regression model (C statistic: 0.87; 95% CI 0.86–0.88) and logistic regression (C statistic: 0.87; 95% CI 0.86–0.87) had lower-but-good discriminative ability. The above results held with validation across both time and sites. Decision curve analysis demonstrated that, although all models provided superior net benefit when clinical decision thresholds were between 0% and 80% predicted risk, the extreme gradient boosting model provided the greatest net benefit.

CONCLUSION:

Postpartum hemorrhage on labor admission can be predicted with excellent discriminative ability using machine learning and statistical models. Further clinical application is needed, which may assist health care providers to be prepared and triage at-risk women.
Diagnosis and Management of Adenocarcinoma in Situ
Authors: Teoh Deanna , Musa Fernanda , Salani Ritu , Huh Warner , Jimenez Edward
Published: March 2020

This publication represents an extensive literature review with the goal of providing guidelines for the evaluation and management of cervical adenocarcinoma in situ (AIS). The authors drafted the guidelines on behalf of the Society of Gynecologic Oncology, and the guidelines have been reviewed and endorsed by the ASCCP. These guidelines harmonize with the ASCCP Risk-Based Management Consensus Guidelines and provide more specific guidance beyond that provided by the ASCCP guidelines. Examples of updates include recommendations to optimize the diagnostic excisional specimen, AIS management in the setting of positive compared with negative margins on the excisional specimen, surveillance and definitive management after fertility-sparing treatment, and management of AIS in pregnancy. The increasing incidence of AIS, its association with human papillomavirus–18 infection, challenges in diagnosis owing to frequent origin within the endocervical canal, and the possibility of skip lesions all make AIS a unique diagnosis whose management needs to be differentiated from the management of the more prevalent squamous cell dysplasia.
Cochrane Review Summaries—April 2020
Authors: Kumar Nimisha , Jahanfar Shayesteh , Haas David M.
Published: March 2020

This feature highlights recently published Cochrane Reviews of interest to the readers of Obstetrics & Gynecology. This month, we focus on two obstetric reviews on umbilical cord clamping and induction of labor and one gynecology review on epithelial ovarian cancer. The brief summaries are published below and the complete references, along with a hyperlink, are listed in Box 1

Box 1. Abstracts Discussed in This Summary

Rabe H, Gyte GML, Díaz-Rossello JL, Duley L. Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes. The Cochrane Database of Systematic Reviews 2019, Issue 9. Art. No.: CD003248. Available at: https://doi.org/10.1002/14651858.CD003248.pub4

de Vaan MDT, ten Eikelder MLG, Jozwiak M, Palmer KR, Davies-Tuck M, Bloemenkamp KWM, et al. Mechanical methods for induction of labour. The Cochrane Database of Systematic Reviews 2019, Issue 10. Art. No.: CD001233. Available at: https://doi.org/10.1002/14651858.CD001233.pub3.

Coleridge SL, Bryant A, Lyons TJ, Goodall RJ, Kehoe S, Morrison J. Chemotherapy versus surgery for initial treatment in advanced ovarian epithelial cancer. The Cochrane Database of Systematic Reviews 2019, Issue 10. Art. No.: CD005343. Available at: https://doi.org/10.1002/14651858.CD005343.pub4.
Bariatric Surgery Population at Significantly Increased Risk of Spinal Disorders and Surgical Intervention Compared With Morbidly Obese Patients
Authors: Passias Peter G. , Horn Samantha R. , Ihejirika Yael U. , Vasques-Montes Dennis , Segreto Frank A. , Bortz Cole A. , Brown Avery E. , Pierce Katherine E. , Alas Haddy , Poorman Gregory W. , Jalai Cyrus M. , Wang Charles , Buza John A. , Steinmetz Leah , Varlotta Christopher G. , Vira Shaleen , Diebo Bassel G. , Hassanzadeh Hamid , Lafage Renaud , Lafage Virginie
Published: March 2020

Introduction:

Obesity is associated with acceleration of musculoskeletal degenerative diseases and functional impairment secondary to spinal disorders. Bariatric surgery (BS) is an increasingly common treatment for severe obesity but can affect bone and mineral metabolism. The effect of BS on degenerative spinal disorders is yet to be fully described. The aim of our study was to analyze changes in bariatric patients’ risk for spinal degenerative diseases and spinal surgery.

Methods:

Retrospective analysis of the prospectively collected New York State Inpatient Database (NYSID) years (2004–2013) using patient linkage codes. The incidence of degenerative spinal diagnoses and spinal surgery was queried using International Classification of Diseases, Ninth Revision (ICD)-9 codes for morbidly obese patients (ICD-9 278.01) with and without a history of BS. The incidence of degenerative spinal diagnoses and spinal surgery was determined using χ2 tests for independence. Logistic testing controlled for age, sex, and comorbidity burden.

Results:

A total of 18,176 patients were identified in the NYSID database with a history of BS and 146,252 patients were identified as morbidly obese without a history of BS. BS patients have a significantly higher rate of spinal diagnoses than morbidly obese patients without BS (19.3% vs. 8.1%, P<0.001). Bariatric patients were more likely to have spinal diagnoses and procedures than nonbariatric obese patients (P<0.001). This was mostly observed in lumbar spinal stenosis (5.0%), cervical disk herniation (3.3%), lumbar disk degeneration (3.4%), lumbar spondylolisthesis (2.9%), lumbar spondylosis (1.9%), and cervical spondylosis with myelopathy (2.0%). Spine procedure rates are higher for bariatric patients than nonbariatric overall (25.6% vs. 2.3, P<0.001) and for fusions and decompressions (P<0.001). When controlling for age, sex, and comorbidities (and diagnosis rate with regards to procedure rates), these results persist, with BS patients having a higher likelihood of spinal diagnoses and procedures. In addition, bariatric patients had a lower comorbidity burden than morbidly obese patients without a history of BS.

Conclusions:

Morbidly obese BS patients have a dramatically higher incidence of spinal diagnoses and procedures, relative to morbidly obese patients without BS. Further study is necessary to determine if there is a pathophysiological mechanism underlying this higher risk of spinal disease and intervention in bariatric patients, and the effect of BS on these rates following treatment.

Level of Evidence:

Level III.
Peer Support as an Ideal Solution for Racial/Ethnic Disparities in Colorectal Cancer Screening: Evidence from a Systematic Review and Meta-analysis
Authors: Hu Jieman , Wu Yuanyu , Ji Fujian , Fang Xuedong , Chen Fangfang
Published: March 2020

BACKGROUND:

Low implementation of colorectal cancer screening in ethnic minorities is the main reason for racial and ethnic disparities in colorectal cancer morbidity and mortality. Peer support is widely used for promoting health care in ethnic minorities. However, whether it improves their acceptance to undergo the screening remains controversial.

OBJECTIVE:

We performed a meta-analysis of the currently available studies to further explore its effectiveness.

DATA SOURCES:

This meta-analysis was undertaken using PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, and PsycINFO for randomized controlled trials.

STUDY SELECTION:

We included studies that compared peer support interventions among ethnic minorities versus other interventions to promote uptake of colorectal cancer screening.

RESULTS:

Thirteen studies comprising 8090 participants met the eligibility criteria. Peer support intervention can increase colorectal cancer screening implementation and raise awareness and intention to undergo the screening in ethnic minorities more significantly than fecal occult blood test outreach, print, and usual care. Subgroup analysis showed that peer support intervention achieved great results in Asian Americans and intervention of peer counseling.

LIMITATIONS:

The results of subgroup analysis had substantial heterogeneity, which may decrease the precision of our estimates.

CONCLUSIONS:

Peer support can significantly improve the awareness about and the intention for receiving colorectal cancer screening in ethnic minorities and is an ideal choice for promoting the screening among ethnic minorities, particularly in a diverse community. Peer support intervention is recommended to promote the implementation of screening in Asian Americans. Peer counseling is worth promoting; however, church-based peer counseling programs require enhanced management to maintain their fidelity.
Response to opioids is dependent on sociability levels
Authors: Madison Caitlin A. , Wellman Paul J. , Eitan Shoshana
Published: March 2020

Social environment influences the trajectory of developing opioid use disorder (OUD). Thus, the present study tested the hypothesis that sociability levels will affect the responses to opioids. Mice were tested for their baseline sociability, anxiety levels, pain sensitivities, and their acute locomotor response to 5 mg/kg opioids. Then, they were administered repeatedly with saline, hydrocodone, or morphine (20 mg/kg for 5 days, and then 40 mg/kg for 5 days). Subsequently, they were examined for the expression of locomotor sensitization and retested for the effects of opioids on their sociability, anxiety levels, and pain sensitivity. On the basis of their baseline sociability level, mice were divided into socially avoiding and socially exploring. Socially avoiding and socially exploring mice did not differ in their baseline weight and anxiety sensitivities. Socially avoiding mice had slightly higher baseline heat sensitivity than those in socially exploring mice. Repeated administration of opioids had differential effects in socially avoiding and socially exploring mice. In both social groups, repeated morphine administration had overall stronger effects compared with hydrocodone. Morphine-treated socially exploring mice developed greater locomotor sensitization than those in morphine-treated socially avoiding mice. Morphine-treated socially avoiding mice, but not socially exploring mice, spent more time in the center zone of the open-field test and in the light zone of light/dark boxes, and developed heat hyperalgesia. This study suggests that socially exploring animals are more sensitive to the sensitizing effects of opioids. In contrast, opioids have greater effects on the stress and pain systems of socially avoiding animals. Thus, the underlying mechanisms for developing OUD might differ in individuals with various sociability levels.
Chrysin Alleviates Monocrotaline-Induced Pulmonary Hypertension in Rats Through Regulation of Intracellular Calcium Homeostasis in Pulmonary Arterial Smooth Muscle Cells
Authors: Dong Fang , Zhang Jun , Chen Xiuqing , Zhang Suya , Zhu Licheng , Peng Yufei , Guo Zhiping
Published: March 2020

Chrysin (CH) is the main ingredient of many medicinal plants. Our previous study showed that CH could suppress hypoxia-induced pulmonary arterial smooth muscle cells proliferation and alleviate chronic hypoxia-induced pulmonary hypertension by targeting store-operated Ca2+ entry (SOCE)-[Ca2+]i pathway. In this study, we investigated the effect of CH on monocrotaline-induced pulmonary hypertension (MCTPH) and the mechanism behind it. Results show that, in MCTPH model rats, (1) CH significantly reduced the enhancement of right ventricular pressure, right ventricular hypertrophy, and pulmonary vascular remodeling; (2) CH markedly suppressed the promotion of SOCE and [Ca2+]i in pulmonary arterial smooth muscle cells; and (3) CH obviously inhibited the MCT-upregulated proliferating cell nuclear antigen, TRPC1, TRPC4, and TRPC6 expression in distal pulmonary arteries. These results demonstrate that CH likely alleviates MCTPH by targeting TRPC1,4,6-SOCE-[Ca2+]i pathway.