bluuebunny/crossref_metadata_2025 huggingface dataset:
Accelerated Hyper-Maturation of Parvalbumin Circuits in the Absence of MeCP2
Authors: Patrizi Annarita , Awad Patricia N , Chattopadhyaya Bidisha , Li Chloe , Di Cristo Graziella , Fagiolini Michela
Published: April 2019

Methyl-CpG-binding protein 2 (MeCP2) mutations are the primary cause of Rett syndrome, a severe neurodevelopmental disorder. Cortical parvalbumin GABAergic interneurons (PV) make exuberant somatic connections onto pyramidal cells in the visual cortex of Mecp2-deficient mice, which contributes to silencing neuronal cortical circuits. This phenotype can be rescued independently of Mecp2 by environmental, pharmacological, and genetic manipulation. It remains unknown how Mecp2 mutation can result in abnormal inhibitory circuit refinement. In the present manuscript, we examined the development of GABAergic circuits in the primary visual cortex of Mecp2-deficient mice. We identified that PV circuits were the only GABAergic interneurons to be upregulated, while other interneurons were downregulated. Acceleration of PV cell maturation was accompanied by increased PV cells engulfment by perineuronal nets (PNNs) and by an increase of PV cellular and PNN structural complexity. Interestingly, selective deletion of Mecp2 from PV cells was sufficient to drive increased structure complexity of PNN. Moreover, the accelerated PV and PNN maturation was recapitulated in organotypic cultures. Our results identify a specific timeline of disruption of GABAergic circuits in the absence of Mecp2, indicating a possible cell-autonomous role of MeCP2 in the formation of PV cellular arbors and PNN structures in the visual cortex.
Network using Michaelis–Menten kinetics: constructing an algorithm to find target genes from expression data
Authors: Krishnan Mythreye , Small Michael , Bosco Anthony , Stemler Thomas
Published: April 2019

The most challenging aspect of gene expression data analysis is to process the large and complex data using mathematical models and find biologically relevant information that gives insight to the underlying mechanism. We derived a simple ordinary differential equation-based model using Michaelis–Menten Kinetics to process the microarray data. Different biological systems of experimental rhinovirus infection in humans, atopic CD4 T cell responses in allergens and responses to cancer immunotherapy in mice have been studied. The resulting analysis extracts highly linked target genes, the changes in which might cause changes in the other genes, in other words, potential targets for modulating gene network patterns and emergent biological phenotypes. We illustrate the application of the algorithm to identify novel targets in addition to previously identified targets in different experimental contexts.
‘Unhappy and Wretched Creatures’: Charity, Poor Relief and Pauper Removal in Britain and Ireland during the Great Famine
Authors: Darwen Lewis , Macraild Donald , Gurrin Brian , Kennedy Liam
Published: April 2019

During the Great Famine (1845–51) hundreds of thousands of Irish refugees fled to Britain, escaping the hunger and disease afflicting their homeland. Many made new lives there, but others were subsequently shipped back to Ireland by poor law authorities under the laws of Settlement and Removal. This article explores the coping strategies of the Famine Irish in Britain, and the responses of poor law authorities to the inflow of refugees with a particular focus on their use of removal. We argue that British poor law unions in areas heavily affected by the refugee crisis adopted rigorous removal policies, and that the non-settled Irish were consequently deeply reluctant to apply for poor relief, doing so only when alternative sources of support were unavailable. Thus, the true scale of Irish hardship was hidden from the official record. The article also explores, for the first time, the experiences of those sent back to Ireland, a country suffering from the devastating effects of Famine. The combination of heavy Irish immigration to Britain and large-scale removals back to Ireland created distrust between the authorities at British and Irish port towns, as both sides felt aggrieved by the inflow of destitute Irish arriving on their shores. At the centre of all this were the Irish poor themselves. Uncertainty, dislocation and hardship were often their experience, and we argue that this endured long after the Famine had ended; that the events of the late 1840s, indeed, created a new reality for the Irish in Britain.
Eliciting Life Priorities of Older Adults Living in Permanent Supportive Housing
Authors: Padgett Deborah K , Bond Lynden , Gurdak Kristen , Henwood Benjamin F
Published: April 2019

Background and Objectives

Adults who have experienced chronic homelessness are considered to be “old” by age 50 due to accelerated aging. While permanent supportive housing (PSH) has been found effective for these individuals, there is limited focus on the needs of adults “aging in place” in PSH. This study examined (1) how older adults in PSH identify and rank their life priorities, (2) how they describe these priorities in their own words, and (3) how life course adversity deepens an understanding of these priorities.

Research Design and Methods

A convergent parallel mixed methods design was used in which qualitative case study analyses informed by a life course perspective provided a deeper understanding of how 14 older residents of PSH viewed their life priorities using quantitative card-sort rankings of 12 life domains.

Results

Housing, family, mental health, physical health, and partner were the most frequently endorsed life priorities. Four themes emerged from the cross-case analyses: “aging in, aging out,” “carefully restoring relationships,” “life goes on,” and “housing is fundamental.” Convergent findings indicated that life adversity—social losses and interrupted lives—influenced both the high- and low-ranked card-sort priorities.

Discussion and Implications

This study demonstrated that participants were aware of their advancing years yet they sought to overcome adversity and losses through maintaining mental health and sobriety, improving physical health, and cautiously rebuilding relationships. As the numbers of older homeless rise, the inclusion of age-related services will be an important component of PSH services for residents as they age.
Psychological flexibility: positive implications for mental health and life satisfaction
Authors: Lucas James J , Moore Kathleen A
Published: April 2019

New wave therapies such as Acceptance and Commitment Therapy aim to cultivate people’s psychological flexibility in order for them to live a satisfying life. Psychological flexibility has also a role in promoting mental health, which may mediate the relationship with life satisfaction. The aim of this study was to determine whether mental health mediates the effect of psychological flexibility on life satisfaction. A convenience sample of 140 adults (32 males, M = 36.50 years, SD = 12.22; 107 females, M = 38.46 years, SD = 12.81; and a 45-year-old person of unknown gender) completed an online questionnaire assessing psychological flexibility, mental health and life satisfaction. Three of the four hypothesized components of psychological flexibility (experiential acceptance, cognitive alternatives and cognitive control) contributed to the latent construct of psychological flexibility, but cognitive defusion failed to contribute. Psychological flexibility had a direct, positive effect on life satisfaction and the hypothesis that mental health would mediate this relationship was supported. The results suggest that psychological flexibility is important for one’s mental health and that both are integral to life satisfaction. The results also support a continued focus on third-wave therapies in cultivating psychological flexibility.
The lysosomal disease caused by mutant VPS33A
Authors: Pavlova Elena V , Shatunov Aleksey , Wartosch Lena , Moskvina Alena I , Nikolaeva Lena E , Bright Nicholas A , Tylee Karen L , Church Heather J , Ballabio Andrea , Luzio J Paul , Cox Timothy M
Published: April 2019

A rare lysosomal disease resembling a mucopolysaccharidosis with unusual systemic features, including renal disease and platelet dysfunction, caused by the defect in a conserved region of the VPS33A gene on human chromosome 12q24.31, occurs in Yakuts—a nomadic Turkic ethnic group of Southern Siberia. VPS33A is a core component of the class C core vacuole/endosome tethering (CORVET) and the homotypic fusion and protein sorting (HOPS) complexes, which have essential functions in the endocytic pathway. Here we show that cultured fibroblasts from patients with this disorder have morphological changes: vacuolation with disordered endosomal/lysosomal compartments and—common to sphingolipid diseases—abnormal endocytic trafficking of lactosylceramide. Urine glycosaminoglycan studies revealed a pathological excess of sialylated conjugates as well as dermatan and heparan sulphate. Lipidomic screening showed elevated β-D-galactosylsphingosine with unimpaired activity of cognate lysosomal hydrolases. The 3D crystal structure of human VPS33A predicts that replacement of arginine 498 by tryptophan will de-stabilize VPS33A folding. We observed that the missense mutation reduced the abundance of full-length VPS33A and other components of the HOPS and CORVET complexes. Treatment of HeLa cells stably expressing the mutant VPS33A with a proteasome inhibitor rescued the mutant protein from degradation. We propose that the disease is due to diminished intracellular abundance of intact VPS33A. Exposure of patient-derived fibroblasts to the clinically approved proteasome inhibitor, bortezomib, or inhibition of glucosylceramide synthesis with eliglustat, partially corrected the impaired lactosylceramide trafficking defect and immediately suggest therapeutic avenues to explore in this fatal orphan disease.
A 45-year experience with the Fontan procedure: tachyarrhythmia, an important sign for adverse outcome
Authors: Rijnberg Friso M , Blom Nico A , Sojak Vladimir , Bruggemans Eline F , Kuipers Irene M , Rammeloo Lukas A J , Jongbloed Monique R M , Bouma Berto J , Hazekamp Mark G
Published: April 2019

OBJECTIVES

This study aims to evaluate our 45-year experience with the Fontan procedure and to identify risk factors for late mortality and morbidity.

METHODS

Demographic, preoperative, perioperative and postoperative characteristics were retrospectively collected for all patients who underwent a Fontan procedure in a single centre between 1972 and 2016.

RESULTS

The study included 277 Fontan procedures (44 atriopulmonary connections, 28 Fontan-Björk, 42 lateral tunnels and 163 extracardiac conduits). Early failure occurred in 17 patients (6.1%). Median follow-up of the study cohort was 11.9 years (Q1–Q3 7.6–17.5). Longest survival estimates were 31% [95% confidence intervals (CI) 18–44%] at 35 years for atriopulmonary connection/Björk, 87% (95% CI 63–96%) at 20 years for lateral tunnel and 99% (95% CI 96–100%) at 15 years for extracardiac conduit. Estimated freedom from Fontan failure (death, heart transplant, take-down, protein-losing enteropathy, New York Heart Association III–IV) at 15 years was 65% (95% CI 52–76%) for atriopulmonary connection/Björk, 90% (95% CI 73–97%) for lateral tunnel and 90% (95% CI 82–94%) for extracardiac conduit. The development of tachyarrhythmia was an important predictor of Fontan failure [hazard ratio (HR) 2.6, 95% CI 1.2–5.8; P = 0.017], thromboembolic/neurological events (HR 3.6, 95% CI 1.4–9.4; P = 0.008) and pacemaker for sinus node dysfunction (HR 3.7, 95% CI 1.4–9.6; P = 0.008). Prolonged pleural effusion (>21 days) increased the risk of experiencing protein-losing enteropathy (HR 4.7, 95% CI 2.0–11.1; P < 0.001).

CONCLUSIONS

With modern techniques, survival and freedom from Fontan failure are good. However, Fontan patients remain subject to general attrition. Tachyarrhythmia is an important sign for an adverse outcome. Prevention and early treatment of tachyarrhythmia may, therefore, be paramount in improving the long-term outcome.
Complete Minors in Graphs Without Sparse Cuts
Authors: Krivelevich Michael , Nenadov Rajko
Published: April 2019

We show that if $G$ is a graph on $n$ vertices, with all degrees comparable to some $d = d(n)$, and without a sparse cut, for a suitably chosen notion of sparseness, then it contains a complete minor of order $$\begin{equation*} \Omega\left( \sqrt{\frac{n d}{\log d}} \right). \end{equation*}$$As a corollary we determine the order of a largest complete minor one can guarantee in $d$-regular graphs for which the 2nd largest eigenvalue is bounded away from $d/2$, in $(d/n, o(d))$-jumbled graphs, and in random $d$-regular graphs, for almost all $d = d(n)$.
Persistence of Antibodies to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: 1-Year Follow-up With Memory Probe Vaccination
Authors: Atmar Robert L , Baehner Frank , Cramer Jakob P , Lloyd Eric , Sherwood James , Borkowski Astrid , Mendelman Paul M ,   NOR-201 Study Group, Al-Ibrahim Mohamed S , Bernstein David L , Brandon Donald M , Chu Laurence , Davis Matthew G , Epstein Robert J , Frey Sharon E , Rosen Jeffrey B , Treanor John J
Published: April 2019

Background

We previously reported the tolerability and immunogenicity 1 month after intramuscular administration of 2 bivalent virus-like particle (VLP)–based candidate norovirus vaccine formulations in adults. We now describe the persistence of immunity and responses to a memory probe vaccination 1 year later.

Methods

A total of 454 healthy men and women aged 18–49 years in 3 equal groups received placebo (saline) or 15/50 or 50/50 vaccine formulations (ie, 15 or 50 µg of GI.1 genotype VLPs, respectively, and 50 µg of GII.4c VLPs) with MPL and Al(OH)3. Immunogenicity and safety were assessed up to day 365, when 351 participants received a memory probe vaccination of 15 µg each of GI.1 and GII.4c VLPs with Al(OH)3.

Results

No safety signals were detected up to 1 year after the first vaccination. Pan-immunoglobulin, immunoglobulin A, and histo-blood group antigen–blocking (HBGA) antibody levels among vaccinees waned but remained higher than levels before vaccination and levels in placebo recipients on days 180 and 365. Memory probe vaccination increased all antibody titers. Levels of HBGA antibodies to GI.1 but not GII.4c were higher after the first vaccination in candidate vaccine groups, compared with those in the placebo group.

Conclusion

Levels of antibodies to both candidate norovirus VLP formulations persisted above baseline levels for at least 1 year after primary vaccination. HBGA-blocking responses to the memory probe for GI.1 but not GII.4c displayed characteristics of immune memory.

Clinical Trials Registration

NCT02142504.
Hepatitis E Virus (HEV) Open Reading Frame 2 Antigen Kinetics in Human-Liver Chimeric Mice and Its Impact on HEV Diagnosis
Authors: Sayed Ibrahim M , Verhoye Lieven , Montpellier Claire , Abravanel Florence , Izopet Jacques , Cocquerel Laurence , Meuleman Philip
Published: April 2019

Background

Hepatitis E virus infection (HEV) is an emerging problem in developed countries. Diagnosis of HEV infection is based on the detection of HEV-specific antibodies, viral RNA, and/or antigen (Ag). Humanized mice were previously reported as a model for the study of HEV infection, but published data were focused on the quantification of viral RNA. However, the kinetics of HEV Ag expression during infection remains poorly understood.

Methods

Plasma specimens and suspensions of fecal specimens from HEV-infected and ribavirin-treated humanized mice were analyzed using HEV antigen–specific enzyme-linked immunosorbent assay, reverse transcription–quantitative polymerase chain reaction analysis, density gradient analysis, and Western blotting.

Result

Open reading frame 2 (ORF2) Ag was detected in both plasma and stool from HEV-infected mice, and levels increased over time. Contrary to HEV RNA, ORF2 Ag levels were higher in mouse plasma than in stool. Interestingly, ORF2 was detected in plasma from mice that tested negative for HEV RNA in plasma but positive for HEV RNA in stool and was detected after viral clearance in mice that were treated with ribavirin. Plasma density gradient analysis revealed the presence of the noninfectious glycosylated form of ORF2.

Conclusion

ORF2 Ag can be used as a marker of active HEV infection and for assessment of the effect of antiviral therapy, especially when fecal samples are not available or molecular diagnostic tests are not accessible.
Structure of the periplasmic domain of SflA involved in spatial regulation of the flagellar biogenesis of Vibrio reveals a TPR/SLR-like fold
Authors: Sakuma Mayuko , Nishikawa Shoji , Inaba Satoshi , Nishigaki Takehiko , Kojima Seiji , Homma Michio , Imada Katsumi
Published: April 2019

Bacteria have evolved various types of flagellum, an organella for bacterial motility, to adapt to their habitat environments. The number and the spatial arrangement of the flagellum are precisely controlled to optimize performance of each type of the flagellar system. Vibrio alginolyticus has a single sheathed flagellum at the cell pole for swimming. SflA is a regulator protein to prevent peritrichous formation of the sheathed flagellum, and consists of an N-terminal periplasmic region, a transmembrane helix, and a C-terminal cytoplasmic region. Whereas the cytoplasmic region has been characterized to be essential for inhibition of the peritrichous growth, the role of the N-terminal region is still unclear. We here determined the structure of the N-terminal periplasmic region of SflA (SflAN) at 1.9-Å resolution. The core of SflAN forms a domain-swapped dimer with tetratricopeptide repeat (TPR)/Sel1-like repeat (SLR) motif, which is often found in the domains responsible for protein–protein interaction in various proteins. The structural similarity and the following mutational analysis based on the structure suggest that SflA binds to unknown partner protein by SflAN and the binding signal is important for the precise control of the SflA function.
PCR-Based Bloodmeal Analysis of Aedes aegypti and Culex quinquefasciatus (Diptera: Culicidae) in St. George Parish, Grenada
Authors: Fitzpatrick Daniel M , Hattaway Lindsey M , Hsueh Andy N , Ramos-Niño Maria E , Cheetham Sonia M
Published: April 2019

Blood-feeding patterns of mosquitoes affect the transmission and maintenance of arboviral diseases. In the Caribbean, Aedes aegypti (L.) and Culex quinquefasciatus Say mosquitoes are the dominant mosquito species in developed areas. However, no information is available on the bloodmeal hosts of these invasive vectors in Grenada, where arboviral pathogens such as dengue, chikungunya, and Zika viruses cause significant human suffering. To this end, Ae. aegypti and Cx. quinquefasciatus mosquitoes were investigated from five semirural locations near houses in St. George’s Parish, from 2017 to 2018. Polymerase chain reaction was conducted on DNA extracted from individual blood-fed mosquitoes using vertebrate-specific cytochrome b primers. The 32 Ae. aegypti bloodmeals included humans (70%), mongooses (18%), domestic dogs (6%), a domestic cat (3%), and an unidentified bird (3%). Thirty-seven Cx. quinquefasciatus mosquitoes took bloodmeals from seven species of birds (51%), humans (27%), domestic cats (8%), iguanas (5%), a domestic dog (3%), a rat (3%), and a common opossum (3%). The high percentage of human bloodmeal hosts in our study, especially by the normally anthropophilic Ae. aegypti, is expected. The bloodmeal sources and the percentage of nonhuman bloodmeals (30%) taken by Ae. aegypti are comparable to other studies. The large range of hosts may be explained in part by the semirural nature of most local housing. Accordingly, this may contribute to an exchange of pathogens between domestic, peridomestic, and sylvatic transmission cycles.
Challenging the Welfare System and Forcing Policy Innovation? Unaccompanied Asylum-seeking Children in Sweden and Germany
Authors: Aflaki Inga Narbutaité , Freise Matthias
Published: April 2019

The article examines from a comparative perspective how Sweden and Germany reacted to the unprecedented increase in unaccompanied asylum-seeking children (UASC) in 2015. Concretely, it analyses on the basis of Windrum’s taxonomy of public-sector innovation what kinds of generic and context-specific policy instruments have been developed for this particularly vulnerable group and discusses whether and to what extent prevailing welfare-service organizational arrangements have changed in the two countries since 2015. By illustrating the reactions of two countries, the study shows that an unprecedented wave of refugees/asylum seekers can trigger both more incremental, adaptive and drastic transformative policy changes. The policy systems of both countries indicate not only some resilience, but also overburdened government capacity and more drastic changes that led to reduction of the legal rights of UASC.
Low S-adenosylmethionine/ S-adenosylhomocysteine Ratio in Urine is Associated with Chronic Kidney Disease
Authors: Kruglova Maria Petrovna , Grachev Sergej Vital’evich , Bulgakova Polina Olegovna , Ivanov Alexander Vladimirovich , Virus Edward Danielevich , Nikiforova Ksenya Alexandrovna , Fedoseev Anatolij Nikolaevich , Savina Galina Dmitrievna , Kubatiev Aslan Amirkhanovich
Published: April 2019

Objective

To evaluate the association of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in urine with chronic kidney disease (CKD).

Methods

Case-control study including 50 patients with CKD and 20 healthy volunteers.

Results

SAM level and SAM/SAH ratio in urine were significantly lower in patients than in control individuals (P <.001 and P = .01, respectively). The estimated glomerular filtration rate was associated with the SAM level (P = .04) and the SAM/SAH ratio in urine (P = .01).

Conclusion

CKD is associated not only with the decline in the SAM level but also with the decrease in the SAM/SAH ratio in urine. Thus, use of the urinary SAM/SAH ratio as a noninvasive diagnostic indicator of renal function seems promising.
Foxr2 promotes formation of CNS-embryonal tumors in a Trp53-deficient background
Authors: Poh Boonmin , Koso Hideto , Momota Hiroyuki , Komori Takashi , Suzuki Yutaka , Yoshida Nobuaki , Ino Yasushi , Todo Tomoki , Watanabe Sumiko
Published: April 2019

Background

Embryonal tumors in the central nervous system (CNS) are primary, aggressive, and poorly differentiated pediatric brain tumors. We identified forkhead box R2 (Foxr2) as an oncogene for medulloblastoma through a transposon-based insertional mutagenesis screen. Foxr2 translocation has been identified in a subset of human embryonal tumors of the CNS, designated as CNS neuroblastoma with Foxr2 activation (CNS NB-Foxr2); however, the in vivo functions of Foxr2 remain elusive.

Methods

We analyzed the effect of Foxr2 overexpression in the mouse brain by generating a transgenic strain that expresses Foxr2 in the entire brain under a transformation related protein 53 (Trp53)–deficient background. We performed histological analysis of tumors and characterized tumor-derived sphere-forming cells. We investigated gene expression profiles of tumor-derived cells.

Results

Foxr2 and Trp53 loss promoted tumor formation in the olfactory bulb (OB) and brainstem (BS). The tumors showed the common morphological features of small round blue cell tumors, exhibiting divergent, mainly neuronal and glial, patterns of differentiation, which corresponds to the definition of CNS-embryonal tumors. Importantly, all mice developed CNS-embryonal tumors. In the OB, early proliferative lesions consisting of oligodendrocyte transcription factor 2 (Olig2+) cells were observed, indicating that Foxr2 expression expanded Olig2+ cells in the OB. Tumor-derived cells formed spheres in vitro and induced tumors that recapitulated the parental tumor upon transplantation, indicating the presence of tumor-initiating cells. Gene expression profiling revealed that OB and BS tumor cells were enriched for the expression of the genes specific to CNS NB-Foxr2.

Conclusion

Our data demonstrate that Foxr2 plays a causative role in the formation of CNS-embryonal tumors.
Heat Stress Suppresses Brassica napus Seed Oil Accumulation by Inhibition of Photosynthesis and BnWRI1 Pathway
Authors: Huang Ruizhi , Liu Zhihong , Xing Meiqing , Yang Yong , Wu Xuelong , Liu Heqin , Liang Weifang
Published: April 2019

Heat stress during Brassica napus seed filling severely impairs yield and oil content. However, the mechanisms underlying heat-stress effects on B. napus seed photosynthesis and oil accumulation remain elusive. In this study, we showed that heat stress resulted in reduction of seed oil accumulation, whereas the seed sugar content was enhanced, which indicated that incorporation of carbohydrates into triacylglycerols was impaired. Photosynthesis and respiration rates, and the maximum quantum yield of photosystem II in developing seeds were inhibited by heat stress. Transcriptome analysis revealed that heat stress led to up-regulation of genes associated with high light response, providing evidence that photoinhibition was induced by heat stress. BnWRI1 and its downstream genes, including genes involved in de novo fatty acid biosynthesis pathway, were down-regulated by heat stress. Overexpression of BnWRI1 with a seed-specific promoter stabilized both oil accumulation and photosynthesis under the heat-stress condition, which suggested BnWRI1 plays an important role in mediating the effect of heat stress on fatty acid biosynthesis. A number of sugar transporter genes were inhibited by heat stress, resulting in defective integration of carbohydrates into triacylglycerols units. The results collectively demonstrated that disturbances of the seed photosynthesis machinery, impairment of carbohydrates incorporation into triacylglycerols and transcriptional deregulation of the BnWRI1 pathway by heat stress might be the major cause of decreased oil accumulation in the seed.
Assessing Reality Testing in Mice Through Dopamine-Dependent Associatively Evoked Processing of Absent Gustatory Stimuli
Authors: Fry Benjamin R , Russell Nicollette , Gifford Ryan , Robles Cindee F , Manning Claire E , Sawa Akira , Niwa Minae , Johnson Alexander W
Published: April 2019

Impairments in reality testing are core features of numerous neuropsychiatric conditions. However, relatively few animal models have been developed to assess this critical facet of neuropsychiatric illness, thus impeding our understanding of the underlying central systems and circuits. Using mice in which dominant-negative Disrupted-in-Schizophrenia-1 is expressed throughout central nervous system circuitry (DN-DISC1-PrP), the capacity for an auditory conditioned stimulus (CS) to evoke perceptual processing of an absent sucrose solution was examined. At test, during CS presentations, DN-DISC1-PrP mice consumed more water and displayed a licking profile that is more typically revealed while ingesting a sweet-tasting solution. DN-DISC1-PrP mice also displayed greater c-fos expression in the insular (gustatory) cortex when consuming water in the presence of the CS. This capacity for the CS to more readily substitute for the taste features of the absent sucrose solution in DN-DISC1-PrP mice was attenuated following systemic treatment with the antipsychotic haloperidol. Conversely, social isolation during adolescence promoted the manifestation of these effects. These results provide strong validation for using associative learning procedures to examine dopamine-mediated reality testing associated with insular cortex activation.
Management of Xanthomonas fragariae with Pre- and Postharvest Treatments to Overcome Trade Barriers for California Strawberries
Authors: Haack Stacey E. , Walse Spencer S. , Nguyen Kevin , Adaskaveg James E.
Published: April 2019

Xanthomonas fragariae, the causal agent of angular leaf spot (ALS) of strawberry, is a quarantine pathogen in some export markets, causing trade restrictions and economic loss to the California fresh-market strawberry industry. Preharvest chemical management options are limited to copper, and there are no postharvest treatments available that reduce populations of the pathogen if ALS is detected at an export destination. Here, we report high preharvest efficacy for the experimental bactericide amino thiadiazole and the commercial product zinc thiadiazole, alone and in mixtures with low rates of copper or the antibiotic kasugamycin, with average disease incidence reduction of up to 92.8% compared with the control. Although effective against quarantine insect pests of strawberry, postharvest methyl bromide fumigation was ineffective against X. fragariae in diseased plant tissue at a standard commercial rate. Postharvest propylene oxide fumigation, used for decades by the California nut industries for insect and microbial disinfestation, significantly reduced X. fragariae populations in infected leaflet tissues by at least 2.5-log compared with controls at a dose of ≥142 µg/ml for 2 h at 15 to 20°C. Fumigated leaflets showed little to no phytotoxicity at effective rates, and fumigated fruit were not significantly affected in appearance or susceptibility to postharvest gray mold or Rhizopus rot following storage at 2°C for 3 days and at 15°C for an additional 5 days. Together, these new treatments offer potential strategies for establishing a systems approach with preharvest treatments significantly reducing the risk of ALS on plants and, in response to quarantine detections, a postharvest fumigation treatment that reduces viable pathogen populations in existing lesions.
Massachusetts' Parental Consent Law and Procedural Timing Among Adolescents Undergoing Abortion
Authors: Janiak Elizabeth , Fulcher Isabel R. , Cottrill Alischer A. , Tantoco Nicole , Mason Ashley H. , Fortin Jennifer , Sabino Jamie , Goldberg Alisa B.
Published: April 2019

OBJECTIVE:

To describe individual-level delay in obtaining abortion associated with use of the Massachusetts judicial bypass system, which legal minors (aged 17 years or younger) use to obtain abortion without consent of a parent or legal guardian in the setting of Massachusetts' parental consent law for abortion.

METHODS:

We conducted a retrospective cohort study of 2,026 abortions among minors at a large, statewide network of abortion clinics between 2010 and 2016. Delay was defined as the number of calendar days between the minor's first call to the clinic to schedule an abortion, and the day the abortion was received.

RESULTS:

In the study population, 1,559 (77%) abortions were obtained with parental consent and 467 (23%) using judicial bypass. Abortions after judicial bypass were more common among minors identifying as Hispanic, non-Hispanic black, or other race, those of low socioeconomic status (as indicated by having Medicaid insurance) and those with a prior birth or prior abortion (all P<.05). Minors with parental consent received their abortion a mean of 8.6 days after initial contact, compared with 14.8 days for minors with judicial bypass, for an unadjusted difference of 6.1 days. In multivariable linear regression modeling adjusting for demographic differences between groups, this difference persisted: minors who obtained abortions after judicial bypass had a significantly greater delay compared with those with parental consent (adjusted mean difference = 5.2 days; 95% CI 4.3 to 6.2). Using multivariable logistic regression modeling, minors with judicial bypass also had higher odds of becoming ineligible for medication abortion between the day of first call and the day of procedure (adjusted odds ratio 1.57; 95% CI 1.09 to 2.26).

CONCLUSION:

Massachusetts' parental consent law for abortion is associated with delay among minors and thereby may constrain the clinical options available to them.
Cystoscopy at the Time of Hysterectomy for Benign Indications and Delayed Lower Genitourinary Tract Injury
Authors: Barber Emma L. , Polan Rosa M. , Strohl Anna E. , Siedhoff Matthew T. , Clarke-Pearson Daniel L.
Published: April 2019

OBJECTIVE:

To compare the rate of delayed 30-day lower genitourinary tract injury in women who underwent cystoscopy at the time of hysterectomy for benign indications to those who did not.

METHODS:

This was a retrospective cohort study of patients who underwent hysterectomy without a concomitant procedure for prolapse or incontinence for benign pathology with a general obstetrician–gynecologist (ob-gyn) recorded in the National Surgical Quality Improvement Program targeted hysterectomy file between 2015 and 2017. The primary outcome was a delayed lower genitourinary tract injury in the 30 days after hysterectomy. Secondary outcomes included urinary tract infection and operative time. The exposure of interest was cystoscopy at the time of hysterectomy. Stratified analysis was performed by route of surgery. Bivariable tests were used to examine associations.

RESULTS:

We identified 39,529 women who underwent hysterectomy for benign indications with a general ob-gyn. Surgical approach was open (26%), laparoscopic or robotic assisted laparoscopic (46%), and vaginal or vaginally assisted (28%). Overall, 25% of women underwent cystoscopy at the time of hysterectomy; cystoscopy was more commonly performed in laparoscopic or robotic (32%) and vaginal hysterectomy (25%) as compared with open hysterectomy (11%) (P<.001). There was no difference in delayed lower genitourinary tract injury between patients who underwent cystoscopy at time of hysterectomy compared with those who did not undergo cystoscopy (0.27% vs 0.24%, P=.64). Patients who underwent cystoscopy were more likely to be diagnosed with a urinary tract infection (2.6% vs 2.0%, RR 1.27 95% CI 1.09–1.47). Median operative time was increased by 17 minutes in cases where cystoscopy was performed (132 vs 115 minutes, P<.001).

CONCLUSION:

Cystoscopy at the time of hysterectomy for benign indications does not result in a lower rate of 30-day delayed lower genitourinary tract injury compared with no cystoscopy.
Reading Level of Online Patient Education Materials From Major Obstetrics and Gynecology Societies
Authors: Fahimuddin Fatimah Z. , Sidhu Sanam , Agrawal Anubhav
Published: April 2019

OBJECTIVE:

To assess whether the readability of online patient education materials provided by eight nationally recognized obstetrics and gynecology societies is in accordance with the recommended 6th-grade reading level outlined by the American Medical Association, National Institute of Health, and United States Department of Health and Human Services.

METHODS:

An analysis of 410 online patient education materials from the American Association of Gynecologic Laparoscopists, the American College of Obstetricians and Gynecologists, the American Society for Reproductive Medicine, the American Urogynecologic Society, the Association of Reproductive Health Professionals, the Society of Gynecologic Oncology, the Society for Maternal-Fetal Medicine, and Voices for Pelvic Floor Disorders was completed, and the readability scores using the Flesch-Kincaid Grade Level, Flesch Reading Ease, Gunning Fog Scale, and Simple Measure of Gobbledygook readability scales were calculated. These scales are used to assess print and web-based written material across a wide range of medical specialties and are endorsed by the National Institutes of Health. All four scales are computer-based assessments of readability that consider word count, number of syllables, and length of sentences when calculating a score that corresponds to grade level.

RESULTS:

Majority of the patient education materials across all eight obstetrics and gynecology societies had readability scores above the recommended 6th-grade reading level. The average reading level for the 69 obstetrics-related articles ranged from 9th to 12th grade. The mean grade level for the 341 gynecology articles had a similar range across the four readability scales.

CONCLUSION:

Online patient education materials provided by major obstetrics and gynecology societies do not currently adhere to recommended readability guidelines. Continued efforts to provide accessible and informative patient education materials is recommended to help improve health literacy for women.
Herbal Medicinal Product Use During Pregnancy and the Postnatal Period
Authors: Muñoz Balbontín Yolanda , Stewart Derek , Shetty Ashalatha , Fitton Catherine A. , McLay James S.
Published: April 2019

OBJECTIVE:

To report the incidence and nature of herbal medicinal products' adverse events and herb–drug interactions used by some pregnant and postnatal women.

DATA SOURCES:

The Allied and Complementary Medicine Database, the Cumulative Index to Nursing and Allied Health Literature, EMBASE, the Cochrane Library, MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov were searched from inception until August 2018.

METHODS OF STUDY SELECTION:

Any studies reporting adverse events, herb–drug interactions or absence thereof associated with herbal medicinal products used during pregnancy or the postnatal period were included. Conference abstracts, pilot studies, and nonhuman studies were excluded. All included studies were critically appraised by two independent reviewers.

TABULATION, INTEGRATION AND RESULTS:

Database searches retrieved 3,487 citations. After duplicate removal and review of titles, abstracts, and full-text, 115 articles were critically appraised. After excluding irrelevant and low-quality articles, 74 articles were included for data extraction and synthesis. Adverse drug reactions, congenital malformations, fetal growth retardation or herb–drug interactions were the primary study objective reported by 19 of the 74 included studies, 16 cohort studies, one cross-sectional survey, and two randomized controlled trials. A total of 47 herbal medicinal products and 1,067,071 women were included in this review. Use of almond oil was associated with preterm birth (odds ratio 2.09, 95% CI 1.07–4.08), oral raspberry leaf was associated with cesarean delivery (adjusted odds ratio [AOR] 3.47, 95% CI 1.45–8.28); heavy licorice use was associated with early preterm birth by 3.07-fold (95% CI 1.17–8.05). African herbal medicine mwanaphepo was associated with maternal morbidity (AOR 1.28; 95% CI 1.09–1.50), and neonatal death or morbidity. Fourteen studies reported absence of adverse events. Four studies reported herb–drug interactions, but none studied adverse events arising from them.

CONCLUSION:

The use of herbal medicinal products during pregnancy and the postnatal period should be discouraged until robust evidence of safety is available.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD42017081058.
Robotic Sacrocolpopexy Simulation Model and Associated Hierarchical Task Analysis
Authors: Myers Erinn M. , Anderson-Montoya Brittany L. , Fasano Heather T. , Vilasagar Smitha , Tarr Megan E.
Published: April 2019

BACKGROUND:

There are limited robotic dry lab training resources that include presacral dissection with vaginal and sacral mesh attachment for robotic sacrocolpopexy. Our objective was to create a simulation model to resemble the anatomy encountered during robotic sacrocolpopexy. Additionally, we sought to outline the steps required to complete a robotic sacrocolpopexy by performing a hierarchical task analysis. With the results of the hierarchical task analysis, we assessed the model's ability to provide an adequate platform for completion of robotic sacrocolpopexy procedural steps.

METHOD:

This observational simulation study was divided into two phases. Phase 1 included model development. Phase 2 involved development of the hierarchical task analysis and assessment of the model.

EXPERIENCE:

After model creation, six experts each performed a robotic sacrocolpopexy using the model. Overall, experts agreed that the model replicated opening the peritoneum, presacral dissection, suturing on the anterior and posterior vagina, and presacral mesh attachment.

CONCLUSION:

We demonstrate construction and use of a robotic sacrocolpopexy simulation model to aid surgeons in training. Further, the hierarchical task analysis provides a method to assess the model's ability to replicate each step of robotic sacrocolpopexy.
Sexual Minority Women's Experiences With Sexual Identity Disclosure in Contraceptive Care
Authors: Greene Madelyne Z. , Carpenter Emma , Hendrick C. Emily , Haider Sadia , Everett Bethany G. , Higgins Jenny A.
Published: April 2019

OBJECTIVE:

To describe a group of young sexual minority women's experiences with and preferences for sexual identity disclosure in the context of contraceptive care.

METHODS:

In Chicago, Illinois, Salt Lake City, Utah, and Madison, Wisconsin, investigators conducted five focus groups (n=22) and 11 interviews with women aged 20–30 years who identified as something other than heterosexual. Focus groups explored social norms regarding contraceptive care; interviews documented individual experiences with contraceptive care. Using a qualitative descriptive approach and combined deductive and inductive content analysis, investigators coded transcripts for themes related to disclosing sexual orientation to contraceptive providers.

RESULTS:

Participants described the process of sexual identity disclosure in contraceptive care in three stages: 1) listening for whether, when, and how health care providers asked about sexual orientation, 2) deciding whether or not to disclose sexual identity to providers, and 3) evaluating responses from providers after disclosure. Participants wanted providers to: avoid assumptions and ask about both sexual identity and sexual behaviors, signal their openness and competence around the health of sexual minority women during contraceptive encounters, and focus discussions on the individual patient's priorities and needs for contraceptive care.

CONCLUSION:

Decisions made by sexual minority women about sexual identity disclosure in contraceptive contexts are influenced by previous and current interactions with health care providers. Contraceptive providers should ask all patients about sexual identity and sexual behavior, avoid assumptions about use of and need for contraception, and acknowledge the prevalence of marginalization, discrimination, and stigma experienced by sexual minority women and their communities in health care contexts.
Uterine Rupture at Term in a Patient With Abdominal Cerclage
Authors: Dandapani Monica , Pflugner Lindsey P. , Fanning Nicole S.
Published: April 2019

BACKGROUND:

When labor ensues in the setting of transabdominal cerclage, uterine rupture is a potential complication associated with significant morbidity and mortality for both mother and fetus.

CASE:

A woman with a transabdominal cerclage presented at 39 2/7 weeks of gestation with contractions, tachycardia, abdominal pain, and fetal bradycardia. Emergent cesarean delivery revealed a ruptured uterus with fetus and placenta floating in the abdomen. Neonatal Apgar scores were 2, 2, and 5 at 1, 5, and 10 minutes of life respectively, with cord pH less than 6.8. After transfusion for the mother and rehabilitation for the neonate, both made a good recovery.

CONCLUSION:

Uterine rupture can be catastrophic, and prevention is paramount. In addition to individualized delivery planning, women with transabdominal cerclage in place should be counseled to present to the hospital immediately in the presence of contractions to prevent poor outcomes.
Accuracy of Three Screening Tools for Prenatal Substance Use
Authors: Coleman-Cowger Victoria H. , Oga Emmanuel A. , Peters Erica N. , Trocin Kathleen E. , Koszowski Bartosz , Mark Katrina
Published: April 2019

OBJECTIVE:

To compare and evaluate the accuracy of three screening tools in identifying illicit drug use and prescription drug misuse among a diverse sample of pregnant women.

METHODS:

This prospective cross-sectional study enrolled a consecutive sample of 500 pregnant women, stratified by trimester, receiving care in two prenatal clinical settings in Baltimore, Maryland, from January 2017 to January 2018. All participants were administered three index tests: 4P's Plus, NIDA Quick Screen-ASSIST (Modified Alcohol, Smoking and Substance Involvement Screening Test), and the SURP-P (Substance Use Risk Profile-Pregnancy) scale, and administered reference tests (urine and hair drug testing) at the in-person baseline visit. To assess test–retest reliability of the index tests, screening tool administrations were repeated 1 week later by telephone. For each screening tool, sensitivity, specificity, positive predictive value, negative predictive value and test–retest reliability were computed. Results were stratified by age, race, and trimester of pregnancy.

RESULTS:

Of the 500 enrolled pregnant women, 494 completed the index screening tools, 497 completed reference testing, and 453 underwent test–retest analysis. For the 4P's Plus, sensitivity=90.2% (84.5, 93.8), and specificity=29.6% (24.4, 35.2). For the NIDA Quick Screen-ASSIST, sensitivity=79.7% (71.2, 84.2), and specificity=82.8% (78.1, 87.1). For the SURP-P, sensitivity=92.4% (87.6, 95.8) and specificity=21.8% (17.4, 27.2). Test–retest reliability (phi correlation coefficients) was 0.84, 0.77, and 0.79 for the 4P's Plus, NIDA Quick Screen-ASSIST and the SURP-P, respectively. For all screening tools, there were differences in validity indices by age and race, but no differences by trimester.

CONCLUSION:

The SURP-P and 4P's Plus had high sensitivity and negative predictive values, making them more ideal screening tests than the NIDA Quick Screen-ASSIST. A clear recommendation for a clinically useful screening tool for prenatal substance use is crucial to allow for prompt and appropriate follow-up and intervention.
Midterm and Long-term Follow-up After Surgical Reconstruction for Lateral Polydactyly of the Foot With Mosaic-like Alignment of the Phalanx Bones
Authors: Iba Kousuke , Ozasa Yasuhiro , Hanaka Megumi , Hayakawa Hikaru , Kanaya Kohei , Yamashita Toshihiko
Published: April 2019

Background:

The phalanx bones in several cases of lateral polydactyly of foot revealed complicated alignment with radiographic findings revealing medial-protrusion and lateral deviation of the middle phalanx. We previously defined such cases as showing “mosaic-like alignment” and demonstrated favorable postoperative outcomes using our surgical procedure. The aim of this study was to evaluate the midterm and long-term postoperative outcomes in such cases.

Methods:

The study included 17 feet from 16 patients; 5 male and 11 female, with one bilateral case. The radiographic findings in all cases revealed a mosaic-like alignment of phalanges. Average age of the patients at the initial surgery was 12 months and average duration of post-operative follow-up was 89 months (60 to 132 mo). The surgical procedures were focused on the alignment between the distal and proximal phalanges independent of the middle phalanx alignment. Ligamentous joint stability was restored using collateral ligament reconstruction. We retrospectively evaluated post-operative outcomes, and subjective evaluation by the patients and parents was carried out.

Results:

No cases revealed either varus or valgus deformities, pigmentation of the grafted skin, or functional disturbance. As for postoperative complications, we observed visible thickening in 7 toes, 3 of which further underwent partial resection of the middle phalanx. Subjective evaluation of the postoperative results by the patients and parents was “very satisfied” or “satisfied” in 15 of 16 cases.

Conclusion:

On the basis of our midterm to long-term postoperative outcomes, we believe that our method of surgical reconstruction provides a new option for the treatment of lateral polydactyly of the foot with mosaic-like alignment of the phalanx bones.

Level of Evidence:

Level IV—therapeutic studies.