bluuebunny/crossref_metadata_2025 huggingface dataset:
A 50-bp enhancer of the mouse acrosomal vesicle protein 1 gene activates round spermatid-specific transcription in vivo†
Authors: Urekar Craig , Acharya Kshitish K , Chhabra Preeti , Reddi Prabhakara P
Published: July 2019

Enhancers are cis-elements that activate transcription and play critical roles in tissue- and cell type-specific gene expression. During spermatogenesis, genes coding for specialized sperm structures are expressed in a developmental stage- and cell type-specific manner, but the enhancers responsible for their expression have not been identified. Using the mouse acrosomal vesicle protein (Acrv1) gene that codes for the acrosomal protein SP-10 as a model, our previous studies have shown that Acrv1 proximal promoter activates transcription in spermatids; and the goal of the present study was to separate the enhancer responsible. Transgenic mice showed that three copies of the −186/−135 fragment (50 bp enhancer) placed upstream of the Acrv1 core promoter (−91/+28) activated reporter expression in testis but not somatic tissues (n = 4). Immunohistochemistry showed that enhancer activity was restricted to the round spermatids. The Acrv1 enhancer failed to activate transcription in the context of a heterologous core promoter (n = 4), indicating a likely requirement for enhancer-core promoter compatibility. Chromatin accessibility assays showed that the Acrv1 enhancer assumes a nucleosome-free state in male germ cells (but not liver), indicating occupancy by transcription factors. Southwestern assays (SWA) identified specific binding of the enhancer to a testis nuclear protein of 47 kDa (TNP47). TNP47 was predominantly nuclear and becomes abundant during the haploid phase of spermatogenesis. Two-dimensional SWA revealed the isoelectric point of TNP47 to be 5.2. Taken together, this study delineated a 50-bp enhancer of the Acrv1 gene for round spermatid-specific transcription and identified a putative cognate factor. The 50-bp enhancer could become useful for delivery of proteins into spermatids.
Follicle-stimulating hormone administration affects amino acid metabolism in mammalian oocytes†
Authors: Tetkova Anna , Susor Andrej , Kubelka Michal , Nemcova Lucie , Jansova Denisa , Dvoran Michal , Del Llano Edgar , Holubcova Zuzana , Kalous Jaroslav
Published: July 2019

Culture media used in assisted reproduction are commonly supplemented with gonadotropin hormones to support the nuclear and cytoplasmic maturation of in vitro matured oocytes. However, the effect of gonadotropins on protein synthesis in oocytes is yet to be fully understood. As published data have previously documented a positive in vitro effect of follicle-stimulating hormone (FSH) on cytoplasmic maturation, we exposed mouse denuded oocytes to FSH in order to evaluate the changes in global protein synthesis. We found that dose-dependent administration of FSH resulted in a decrease of methionine incorporation into de novo synthesized proteins in denuded mouse oocytes and oocytes cultured in cumulus-oocyte complexes. Similarly, FSH influenced methionine incorporation in additional mammalian species including human. Furthermore, we showed the expression of FSH-receptor protein in oocytes. We found that major translational regulators were not affected by FSH treatment; however, the amino acid uptake became impaired. We propose that the effect of FSH treatment on amino acid uptake is influenced by FSH receptor with the effect on oocyte metabolism and physiology.
Shift in flowering time allows diploid and autotetraploid Anacamptis pyramidalis (Orchidaceae) to coexist by reducing competition for pollinators
Authors: Pegoraro Luca , De Vos Jurriaan M , Cozzolino Salvatore , Scopece Giovanni
Published: July 2019

How autopolyploids establish when competing with diploid progenitors is still poorly understood. Here, we investigate the effects of morphological and phenological divergence on the reproductive success of co-occurring diploid and autotetraploid individuals of Anacamptis pyramidalis to disentangle the mechanisms allowing their c-oexistence. We estimated reproductive success in terms of absolute and relative fruit production and recorded morphological and phenological traits of the two cytotypes. We also estimated correlations between traits within cytotypes and the related phenotypic selection patterns. The two cytotypes experience similar levels of reproductive success, but they differ significantly in their morphological and phenological traits. Correlations among floral traits were weaker in autotetraploids than in diploids, but among-individuals variation was higher in diploids. For most flower traits, the strength of phenotypic selection was different in the two cytotypes. We found selection on flower number in both cytotypes, whereas selection for earlier flowering time was only found in late-flowering diploids. Our results suggest that a shift in flowering time may have allowed diploid and autotetraploid A. pyramidalis individuals to reduce competition for naïve pollinators. Consequently, the two cytotypes can coexist by attaining similar levels of reproductive success and, at same time, reducing the likelihood of inter-cytotype mating.
Home run—results of a chronic kidney disease Telemedicine Patient Education Study
Authors: Easom Andrea M , Shukla Ashutosh M , Rotaru Dumitru , Ounpraseuth Songthip , Shah Sudhir V , Arthur John M , Singh Manisha
Published: July 2019

Background

Chronic kidney disease (CKD) incidence is increasing and associated mortality and morbidity are high. Educating patients is effective in delaying progression and establishing optimal renal replacement therapy (RRT). Tele-education/telemedicine (TM) can be an effective tool to provide such education, but there are no available data quantifying its effectiveness. We attempted to establish such evidence correlating the effect of education in patient choices and with the start of actual RRT. We present results from a 3-year pilot study evaluating the effectiveness of comprehensive predialysis education (CPE) through TM for CKD patients compared with a standard care group [face to face (FTF)]. The patient’s ability to choose RRT was the primary endpoint.

Methods

This was a randomized controlled study providing CPE over three classes at nine sites (one FTF and eight TM). Three assessment tools were utilized to compare groups: CKD knowledge, literacy and quality of life.

Results

A total of 47.1% of FTF and 52.2% of TM patients reported not having enough information to choose a modality. This decreased by the third visit (FTF 7.4%, TM 13.2%). Home modality choices more than doubled in both groups (FTF 25.8–67.7%, TM 22.2–50.1%). In patients that completed one visit and needed to start RRT, 47% started on a home modality or received a pre-emptive transplant (home hemodialysis 6%, peritoneal dialysis 38%, transplant 3%).

Conclusions

Results show almost 90% (TM 87%, FTF 95%) of the attendees could choose a modality after education. Home modality choices doubled. Patients were able to make an informed choice regardless of the modality of education.
Indian Interpreters in the Making of Colonial Historiography: New Light on Mark Wilks’s Historical Sketches of the South of India (1810–1817)
Authors: Ng Su Fang
Published: July 2019

A forgotten archive at Oxford, the working library of Mark Wilks (1759–1831), sometime Resident of Madras who wrote the influential Historical Sketches of the South of India (1810), offers evidence of Anglo-Indian collaboration in the early colonial period following the 1799 defeat of Tipu Sultan. Examining new manuscript evidence, this article shows how Wilks, a friend of Colin Mackenzie, the surveyor of Mysore, used texts from the vast Mackenzie Collection to compose his history, abstracting selected translations for his own library. Wilks had the help of Mackenzie’s assistants, in particular Kavali Venkata Lakshmayya. Lakshmayya (and others) provided Wilks with translations of land grants and genealogical narratives, both of which were used to establish historical chronology. Because the British saw themselves as restorers of ancient Indian practices, chronology was as important for public policy as for historiography. Working with Wilks, Lakshmayya compiled a large manuscript folio that was at once a table to convert dates among western, Islamic, and Indian calendars, and a historical abstract giving a timeline of key events. This and other manuscripts show Wilks’s use of the Mackenzie Collection beyond only inscriptions. Historical chronology was established through a mix of sources: inscriptions, narrative accounts, and published works. Moreover, Wilks incorporated narratives written by native interpreters into Historical Sketches. Indian history was the result of Anglo-Indian collaboration. Native interpreters contributed significant intellectual labour, and their historiographical work laid the foundation for the writing of the early history of South India.
Impact of pulmonary function on pulmonary complications after robotic-assisted thoracoscopic lobectomy
Authors: Cao Christopher , Louie Brian E , Melfi Franca , Veronesi Giulia , Razzak Rene , Romano Gaetano , Novellis Pierluigi , Ranganath Neel K , Park Bernard J
Published: July 2019

OBJECTIVES

Percentage-predicted forced expiratory volume in 1 s (FEV1) and diffusing capacity for carbon monoxide (DLCO), and their predicted postoperative (ppo) values are established prognostic factors for postoperative pulmonary complications after thoracotomy. However, their predictive value for minimally invasive pulmonary resections remains controversial. This study assessed the incidence of pulmonary complications after robotic lobectomy for primary lung cancer and analysed the predictive significance of FEV1 and DLCO.

METHODS

This was a retrospective analysis of patients who underwent robotic lobectomy from 4 institutions. Descriptive and comparative analyses were performed for patients who experienced pulmonary complications versus patients who did not, in relation to FEV1 and DLCO values. To identify thresholds for increased complications, patients were categorized into groups of 10% incremental increases in FEV1 and DLCO, and their ppo values.

RESULTS

From November 2002 to April 2018, 1088 patients underwent robotic lobectomy. Overall, 169 postoperative pulmonary complications occurred in 141 patients. Male gender and Eastern Cooperative Oncology Group grade ≥1 were associated with increased pulmonary complications on univariable analysis. Patients who experienced pulmonary complications had increased mortality (2.1% vs 0.2%, P = 0.017) and longer hospitalizations (9 vs 4 days, P < 0.001). Pulmonary complications were associated when FEV1 ≤60% and DLCO ≤50%, and when ppo FEV1 or DLCO was ≤50%; ppo FEV1 ≤50% (P < 0.001) and ppo DLCO ≤50% (P = 0.031) remained statistically significant on multivariable analysis.

CONCLUSIONS

Both FEV1 and DLCO were shown to be significant predictors of pulmonary complications. Furthermore, thresholds of percentage-predicted and ppo FEV1 and DLCO values were identified, below which pulmonary complications occurred significantly more frequently, suggesting their predictive values are particularly useful in patients with poorer pulmonary function.
Annuloplasty ring dehiscence after mitral valve repair: incidence, localization and reoperation
Authors: Noack Thilo , Kiefer Philipp , Vivell Nina , Sieg Franz , Marin-Cuartas Mateo , Leontyev Sergey , Holzhey David Michael , Garbade Jens , Pfannmueller Bettina , Davierwala Piroze , Misfeld Martin , Seeburger Joerg , Borger Michael Andrew
Published: July 2019

OBJECTIVES

Mitral valve (MV) annuloplasty ring dehiscence with subsequent recurrent mitral regurgitation represents an unusual but challenging clinical problem. Incidence, localization and outcomes for this complication have not been well defined.

METHODS

From 1996 to 2016, a total of 3478 patients underwent isolated MV repair with ring annuloplasty at the Leipzig Heart Centre. Of these patients, 57 (1.6%) underwent reoperation due to annuloplasty ring dehiscence. Echocardiographic data, operative and early postoperative characteristics as well as short- and long-term survival rates after MV reoperation were analysed.

RESULTS

Occurrences of ring dehiscence were acute (<30 days), early (≤1 year) and late (>1 year) in 44%, 33% and 23% of patients, respectively. Localization of annuloplasty ring dehiscence was found most frequently in the P3 segment (68%), followed by the P2 (51%) and the P1 segments (47%). The 30-day mortality rate and 1- and 5-year survival rates after MV reoperation were 2%, 89% and 74%, respectively. During reoperation, MV replacement was performed in 38 (67%) and MV re-repair in 19 (33%) patients.

CONCLUSIONS

Annuloplasty ring dehiscence is clinically less common, localized more frequently on the posterior annulus and occurs mostly acutely or early after MV repair. MV reoperation can be performed safely in such patients.
Periodontal effects and survival rates of different mandibular retainers: comparison of bonding technique and wire thickness
Authors: Gökçe Begüm , Kaya Burçak
Published: July 2019

Objectives

This non-randomized prospective cohort study aimed to compare the periodontal effects and success rates of mandibular canine-to-canine fixed retainers having different bonding techniques and wire thicknesses.

Materials and methods

Hundred patients requiring retention after orthodontic treatment were assigned to five study groups (n = 20 in each group, 61 females/39 males, median age range 16.5–18.0 years). Retention was provided by 0.0215”/direct, 0.0215”/indirect, 0.0175”/direct, 0.0175”/indirect bonded multistranded wires and removable Essix appliances. The primary and secondary outcomes were periodontal effects and success rates. The patients were examined in 1 week, 1 month, 3 months and 6 months follow-up appointments. Plaque index, gingival index, probing depth, marginal recession, bleeding on probing, failure rate per retainer wire and survival of retainer wires were analysed by Kruskal–Wallis H, Mann–Whitney U and chi-square tests.

Results

Significant differences were observed between the fixed retainer (FR) and Essix (E) groups in gingival index scores at 1 month [mean FR: 1.13 (95% confidence interval (CI): 0.81–1.44), mean E: 0.40 (95% CI: 0.14–0.69), mean difference: 0.73, P < 0.01], 3 months [mean FR: 0.97/1.01 (95% CI: 0.65–1.30/0.72–1.30), mean E: 0.52 (95% CI: 0.25–0.82), mean differences: 0.45/0.49, P < 0.05], 6 months [mean FR: 0.94 (95% CI: 0.62–1.27), mean E: 0.35 (95% CI: 0.15–0.58), mean difference: 0.59, P < 0.05] and in bleeding on probing scores at 1 month [mean FR: 3.05 (95% CI: 2.12–3.98), mean E: 1.15 (95% CI: 0.42–1.88), mean difference: 1.90, P < 0.01]. The survival rates of retainer wires were 85 per cent for the 0.0215” direct/indirect and 90 per cent for the 0.0175” direct/indirect groups for the 6 months follow-up.

Limitations

Six months follow-up period, which demonstrates only short-term outcomes.

Conclusions

The periodontal outcomes or survival rates of mandibular fixed retainers were not affected by bonding technique or wire thickness, whereas gingival health improved with Essix retainers but not with fixed retainers.
Laboratory observations of frequency-dependent ultrasonic P-wave velocity and attenuation during methane hydrate formation in Berea sandstone
Authors: Sahoo Sourav K , North Laurence J , Marín-Moreno Hector , Minshull Tim A , Best Angus I
Published: July 2019

Knowledge of the effect of methane hydrate saturation and morphology on elastic wave attenuation could help reduce ambiguity in seafloor hydrate content estimates. These are needed for seafloor resource and geohazard assessment, as well as to improve predictions of greenhouse gas fluxes into the water column. At low hydrate saturations, measuring attenuation can be particularly useful as the seismic velocity of hydrate-bearing sediments is relatively insensitive to hydrate content. Here, we present laboratory ultrasonic (448–782 kHz) measurements of P-wave velocity and attenuation for successive cycles of methane hydrate formation (maximum hydrate saturation of 26 per cent) in Berea sandstone. We observed systematic and repeatable changes in the velocity and attenuation frequency spectra with hydrate saturation. Attenuation generally increases with hydrate saturation, and with measurement frequency at hydrate saturations below 6 per cent. For hydrate saturations greater than 6 per cent, attenuation decreases with frequency. The results support earlier experimental observations of frequency-dependent attenuation peaks at specific hydrate saturations. We used an effective medium rock-physics model which considers attenuation from gas bubble resonance, inertial fluid flow and squirt flow from both fluid inclusions in hydrate and different aspect ratio pores created during hydrate formation. Using this model, we linked the measured attenuation spectral changes to a decrease in coexisting methane gas bubble radius, and creation of different aspect ratio pores during hydrate formation.
Disease modeling of core pre-mRNA splicing factor haploinsufficiency
Authors: Wood Katherine A , Rowlands Charlie F , Qureshi Wasay Mohiuddin Shaikh , Thomas Huw B , Buczek Weronika A , Briggs Tracy A , Hubbard Simon J , Hentges Kathryn E , Newman William G , O’Keefe Raymond T
Published: July 2019

The craniofacial disorder mandibulofacial dysostosis Guion-Almeida type is caused by haploinsufficiency of the U5 snRNP gene EFTUD2/SNU114. However, it is unclear how reduced expression of this core pre-mRNA splicing factor leads to craniofacial defects. Here we use a CRISPR-Cas9 nickase strategy to generate a human EFTUD2-knockdown cell line and show that reduced expression of EFTUD2 leads to diminished proliferative ability of these cells, increased sensitivity to endoplasmic reticulum (ER) stress and the mis-expression of several genes involved in the ER stress response. RNA-Seq analysis of the EFTUD2-knockdown cell line revealed transcriptome-wide changes in gene expression, with an enrichment for genes associated with processes involved in craniofacial development. Additionally, our RNA-Seq data identified widespread mis-splicing in EFTUD2-knockdown cells. Analysis of the functional and physical characteristics of mis-spliced pre-mRNAs highlighted conserved properties, including length and splice site strengths, of retained introns and skipped exons in our disease model. We also identified enriched processes associated with the affected genes, including cell death, cell and organ morphology and embryonic development. Together, these data support a model in which EFTUD2 haploinsufficiency leads to the mis-splicing of a distinct subset of pre-mRNAs with a widespread effect on gene expression, including altering the expression of ER stress response genes and genes involved in the development of the craniofacial region. The increased burden of unfolded proteins in the ER resulting from mis-splicing would exceed the capacity of the defective ER stress response, inducing apoptosis in cranial neural crest cells that would result in craniofacial abnormalities during development.
Oestrogen dose tapering during luteal phase does not affect clinical outcomes after hormone replacement treatment–frozen-thawed embryo transfer cycles: a retrospective analysis
Authors: Jing Zhao , Xi Huang , Qianling Zeng , Lunquan Sun , Nenghui Liu , Yanping Li
Published: July 2019

STUDY QUESTION

Does oestrogen dose tapering during the luteal phase affect the clinical outcome after hormone replacement treatment–frozen-thawed embryo transfer (HRT-FET) cycles?

SUMMARY ANSWER

Our results suggest that tapering oestrogen doses during the luteal phase results in similar clinical outcomes to those obtained with the traditional luteal phase support (LPS).

WHAT IS KNOWN ALREADY

Traditional LPS with oestrogen and progesterone is considered necessary in HRT-FET cycles. However, case reports have shown successful clinical pregnancies and live births in the absence of oestrogen administration after embryo transfers.

STUDY DESIGN, SIZE, DURATION

This was a retrospective study on 6035 HRT-FET cycles extending over 7 years from January 2011 to June 2018 at the reproductive medicine centre of Xiangya Hospital.

PARTICIPANTS/MATERIALS, SETTING, METHODS

We compared the clinical outcomes of 1632 HRT-FET cycles with tapered oestrogen doses from 12 days after embryo transfer (study group) to those of 4403 HRT-FET cycles maintained on constant oestrogen doses during the luteal phase (control group) in the case of positive serum HCG test.

MAIN RESULTS AND THE ROLE OF CHANCE

We found similar biochemical pregnancy rates (52.1% vs. 51.9, P = 0.864), clinical pregnancy rates (44.9% vs. 43.2%, P = 0.249), implantation rates (29.8% vs. 29.3%, P = 0.591) and miscarriage rates (16.0% vs. 14.6%, P = 0.379) between the studied groups.

LIMITATIONS, REASONS FOR CAUTION

Retrospective, design-associated biases are possible. In addition, some baseline characteristics differed between groups. Finally, we did not compare live birth rates between groups.

WIDER IMPLICATIONS OF THE FINDINGS

Our study showing similar outcomes between traditional LPS and oestrogen tapering during the luteal phase indicates that oestrogen may be cautiously tapered during the luteal phase after HRT-FET cycles.

STUDY FUNDING/COMPETING INTEREST(S)

This work was supported by the National Natural Science Foundation of China (grant no. 81401269) and the class General Financial Grant from the China Postdoctoral Science Foundation (grant no. 2017M620360). The authors declare that they have no competing interests.

TRIAL REGISTRATION NUMBER

N/A
Laboratory Safety, Biosecurity, and Responsible Animal Use
Authors: McCormick-Ell Jessica , Connell Nancy
Published: July 2019

Research with animals presents a wide array of hazards, some of which overlap those in the in vitro research laboratory. The challenge for environmental health and safety professionals when making their recommendations and performing the risk assessment is to balance worker safety with animal safety/welfare. The care and husbandry of animals require procedures and tasks that create aerosols and involve metabolized chemicals and a variety of physical hazards that must be assessed in addition to the research related risks, all while balancing the biosecurity of the facility and NIH animal care requirements. Detailed communication between health and safety, research, and animal care teams is essential to understand how to mitigate the risks that are present and if modifications need to be made as the experiments and processes progress and change over time. Additionally, the backgrounds and education levels of the persons involved in animal research and husbandry can be quite broad; the training programs created need to reflect this. Active learning and hands-on training are extremely beneficial for all staff involved in this field. Certain areas of research, such as infectious disease research in high- and maximum-containment (biosafety level 3 and 4) facilities, present challenges that are not seen in lower containment or chemical exposure experiments. This paper reviews potential hazards and mitigation strategies and discusses unique challenges for safety at all biosafety levels.
Vaginal Epithelial Cells Discriminate Between Yeast and Hyphae of Candida albicans in Women Who Are Colonized or Have Vaginal Candidiasis
Authors: Roselletti Elena , Perito Stefano , Sabbatini Samuele , Monari Claudia , Vecchiarelli Anna
Published: July 2019

Background

Vaginal candidiasis is common disease affecting women; however, how Candida albicans shift from commensalism towards a pathogenic status remains poorly understood. The present study investigated the vaginal epithelial cell (EC) response dynamics under various conditions.

Methods

Healthy women, asymptomatic C. albicans carriers, and symptomatic patients with vaginal candidiasis were enrolled in this study. ECs in vaginal swabs were analyzed with cytofluorimetric analysis for pattern recognition receptors and intracellular signals, with lactate dehydrogenase assay performed for cell damage, and an enzyme-linked immunosorbent assay for cytokine expression.

Results

The level of toll-like receptor 4 (TLR4), TLR2, and erythropoietin-producing hepatoma A2 (EphA2) expression was significantly higher in ECs from asymptomatic and symptomatic subjects compared to healthy subjects. Activation of transcription factors, nuclear factor-κB (NF-κB) and c-Fos–p-38, was observed in ECs from symptomatic and asymptomatic pseudohyphae/hyphae carriers but not from the asymptomatic yeast carriers. EC damage was only observed in symptomatic patients.

Conclusions

The presence of pseudohyphae/hyphae is required to determine vaginal candidiasis; however, it may be not sufficient to induce the pathologic process associated with neutrophil recruitment and EC damage. This study sheds light on the ambiguous role of the hyphal form during vaginal human commensalism.
Reducing drug prescription errors and adverse drug events by application of a probabilistic, machine-learning based clinical decision support system in an inpatient setting
Authors: Segal G , Segev A , Brom A , Lifshitz Y , Wasserstrum Y , Zimlichman E
Published: July 2019

Background

Drug prescription errors are made, worldwide, on a daily basis, resulting in a high burden of morbidity and mortality. Existing rule-based systems for prevention of such errors are unsuccessful and associated with substantial burden of false alerts.

Objective

In this prospective study, we evaluated the accuracy, validity, and clinical usefulness of medication error alerts generated by a novel system using outlier detection screening algorithms, used on top of a legacy standard system, in a real-life inpatient setting.

Materials and Methods

We integrated a novel outlier system into an existing electronic medical record system, in a single medical ward in a tertiary medical center. The system monitored all drug prescriptions written during 16 months. The department’s staff assessed all alerts for accuracy, clinical validity, and usefulness. We recorded all physician’s real-time responses to alerts generated.

Results

The alert burden generated by the system was low, with alerts generated for 0.4% of all medication orders. Sixty percent of the alerts were flagged after the medication was already dispensed following changes in patients’ status which necessitated medication changes (eg, changes in vital signs). Eighty-five percent of the alerts were confirmed clinically valid, and 80% were considered clinically useful. Forty-three percent of the alerts caused changes in subsequent medical orders.

Conclusion

A clinical decision support system that used a probabilistic, machine-learning approach based on statistically derived outliers to detect medication errors generated clinically useful alerts. The system had high accuracy, low alert burden and low false-positive rate, and led to changes in subsequent orders.
Complete Post-mortem Investigations in a Death Involving Clenbuterol After Long-term Abuse
Authors: Kintz Pascal , Gheddar Laurie , Ameline Alice , Dumestre-Toulet Véronique , Verschoore Marion , Comte Julien , Raul Jean-Sébastien
Published: July 2019

The body of a 61-year-old man was found at his home by his wife, lying on the floor, near the bathroom, around midnight. He was known to be training for bodybuilding, using anabolic steroids. Police investigations revealed the presence of two types of tablets at home, one supposed to contain clenbuterol (0.040 mg) and the other stanozolol (10 mg). Testing the tablets revealed different dosages from what was expected, i.e., 0.073 and 11.5 mg/tablet, for clenbuterol and stanozolol, respectively. External body examination and autopsy, which was performed the next day, revealed generalized organ congestion and lack of any traumatic injury (confirmed by radiology). Cardiomegaly, with a heart weighing 692 g, was obvious. Anatomic pathology tests did not reveal evidence of malformations, but atheromatous plaque was identified in the coronaries during complete histology investigations. Femoral blood, urine, bile, gastric contents and two strands of hair (6 cm) were collected for toxicology. These specimens were submitted to standard analyses, but also to a specific LC–MS-MS method for clenbuterol and stanozolol testing. Clenbuterol was identified in all the tissues, including femoral blood (1.1 ng/mL), urine (7.2 ng/mL), bile (2.4 ng/mL), gastric content (3.2 ng/mL) and hair (23 pg/mg). Stanozolol only tested positive in hair (11 pg/mg). All other analyses were negative, including blood alcohol and drugs of abuse. The pathologists concluded to cardiac insufficiency with support of cardiomegaly, in a context involving repetitive abuse of anabolic drugs. This case indicates that more attention should be paid to clenbuterol, a drug widely used as a stimulant by people who want to lose weight, athletes and bodybuilding practitioners.
Propofol alleviates oxidative stress via upregulating lncRNA-TUG1/Brg1 pathway in hypoxia/reoxygenation hepatic cells
Authors: Ming Nuo , Na Ha Sen Ta , He Jin-Ling , Meng Qing-Tao , Xia Zhong-Yuan
Published: July 2019

Reducing oxidative stress is an effective method to prevent hepatic ischaemia/reperfusion injury (HIRI). This study focuses on the role of propofol on the oxidative stress of hepatic cells and the involved lncRNA-TUG1/Brahma-related gene 1 (Brg1) pathway in HIRI mice. The mouse HIRI model was established and was intraperitoneally injected with propofol postconditioning. Hepatic injury indexes were used to evaluate HIRI. The oxidative stress was indicated by increasing 8-isoprostane concentration. Mouse hepatic cell line AML12 was treated with hypoxia and subsequent reoxygenation (H/R). The targeted regulation of lncRNA-TUG1 on Brg1 was proved by RNA pull-down, RIP (RNA-binding protein immunoprecipitation) and the expression level of Brg1 responds to silencing or overexpression of lncRNA-TUG1. Propofol alleviates HIRI and induces the upregulation of lncRNA-TUG1 in the mouse HIRI model. Propofol increases cell viability and lncRNA-TUG1 expression level in H/R-treated hepatic cells. In H/R plus propofol-treated hepatic cells, lncRNA-TUG1 silencing reduces cell viability and increased oxidative stress. LncRNA-TUG1 interacts with Brg1 protein and keeps its level via inhibiting its degradation. Brg1 overexpression reverses lncRNA-TUG1 induced the reduction of cell viability and the increase in oxidative stress. LncRNA-TUG1 silencing abrogates the protective role of propofol against HIRI in the mouse HIRI model. LncRNA-TUG1 has a targeted regulation of Brg1, and thereby affects the oxidative stress induced by HIRI. This pathway mediates the protective effect of propofol against HIRI of hepatic cell.
Deciphering the mechanism for induction of senescence-associated secretory phenotype (SASP) and its role in ageing and cancer development
Authors: Ohtani Naoko
Published: July 2019

Cellular senescence is an irreversible form of cell cycle arrest that can be induced by persistent DNA damage, and is well known to function as an important tumour suppression mechanism. Cellular senescence is detected in aged organisms; thus, it is also recognized as a hallmark of organismal ageing. Unlike apoptotic cells, senescent cells can survive for long periods of time. Recently, it has been shown that the late stage of senescent cells are capable of expressing a variety of secreted proteins such as cytokines, chemokines and proteases, and this condition is now known as senescence-associated secretory phenotype (SASP). These secreted factors are involved in myriad of physiological functions including tissue repair and clearance of damaged cells. Alternatively, these factors may promote detrimental effects, such as chronic inflammation or cancer progression, should the SASP persist. Recent scientific advances have indicated that innate immune responses, particularly involving the cGAS–STING pathway, trigger SASP induction. Therefore, developing a strategy to regulate SASP may provide scientific insights for the management of age-associated diseases and the implementation of healthy ageing in the future.
Fire Pit-Related Burn Injuries in Children and Adolescents
Authors: Flaherty Michael R , Sheridan Robert
Published: July 2019

Thermal burns are a leading cause of preventable injury in children and adolescents. Fire pits have become increasingly popular outdoor fixtures in U.S. homes. We aimed to identify trends in pediatric burn injuries related to fire pits that presented to a representative sample of United States Emergency Departments (EDs). A retrospective analysis of annual ED visits from the National Electronic Injury Surveillance System (NEISS) from January 1, 2006 through December 31, 2017 using product codes specific to fire pits. U.S. Census population estimates were used to compute rates per 100,000 population. SAS and Joinpoint weighted regression analyses were used to analyze annual estimates and rate trends across the study period. There were 10,951 (95% CI = 8535–13,367) ED visits for burn injuries secondary to outdoor fire pits in patients 19 years of age and younger across the study period. The majority of injuries occurred in children under the age of 5, and were related to falls into or on a hot fire pit. The annual modeled rate change showed an overall significant increase in burn injuries of 7.16 per 100,000 annually from 2006 to 2017 (P = .02). Outdoor fire pits represent an increasing hazard to young children who are particularly susceptible to burn injuries from falls in or around lit recreational fires. Product modifications and public awareness campaigns are necessary to prevent future life-altering injuries in pediatric patients.
Non-proteolytic ubiquitination of OTULIN regulates NF-κB signaling pathway
Authors: Zhao Mengmeng , Song Kun , Hao Wenzhuo , Wang Lingyan , Patil Girish , Li Qingmei , Xu Lingling , Hua Fang , Fu Bishi , Schwamborn Jens C , Dorf Martin E , Li Shitao
Published: July 2019

NF-κB signaling regulates diverse processes such as cell death, inflammation, immunity, and cancer. The activity of NF-κB is controlled by methionine 1-linked linear polyubiquitin, which is assembled by the linear ubiquitin chain assembly complex (LUBAC) and the ubiquitin-conjugating enzyme UBE2L3. Recent studies found that the deubiquitinase OTULIN breaks the linear ubiquitin chain, thus inhibiting NF-κB signaling. Despite the essential role of OTULIN in NF-κB signaling has been established, the regulatory mechanism for OTULIN is not well elucidated. To discover the potential regulators of OTULIN, we analyzed the OTULIN protein complex by proteomics and revealed several OTULIN-binding proteins, including LUBAC and tripartite motif-containing protein 32 (TRIM32). TRIM32 is known to activate NF-κB signaling, but the mechanism is not clear. Genetic complement experiments found that TRIM32 is upstream of OTULIN and TRIM32-mediated NF-κB activation is dependent on OTULIN. Mutagenesis of the E3 ligase domain showed that the E3 ligase activity is essential for TRIM32-mediated NF-κB activation. Further experiments found that TRIM32 conjugates polyubiquitin onto OTULIN and the polyubiquitin blocks the interaction between HOIP and OTULIN, thereby activating NF-κB signaling. Taken together, we report a novel regulatory mechanism by which TRIM32-mediated non-proteolytic ubiquitination of OTULIN impedes the access of OTULIN to the LUBAC and promotes NF-κB activation.
Adulticide Resistance Status of Aedes albopictus (Diptera: Culicidae) in Sabah, Malaysia: A Statewide Assessment
Authors: Elia-Amira N M R , Chen C D , Low V L , Lau K W , Haziqah-Rashid A , Amelia-Yap Z H , Lee H L , Sofian-Azirun M
Published: July 2019

Resistance status of Aedes albopictus (Diptera: Culicidae) collected from Sabah, East Malaysia, was evaluated against four major classes of adulticides, namely pyrethroid, carbamate, organochlorine, and organophosphate. Adult bioassays conforming to WHO standard protocols were conducted to assess knockdown and mortality rates of Ae. albopictus. Among tested pyrethroid adulticides, only cyfluthrin, lambda-cyaholthrin, and deltamethrin were able to inflict total knockdown. The other adulticide classes mostly failed to cause any knockdown; the highest knockdown rate was only 18.33% for propoxur. With regards to mortality rate, Ae. albopictus was unanimously susceptible toward all pyrethroids, dieldrin, and malathion, but exhibited resistance toward bendiocarb, propoxur, dichlorodiphenyltrichloroethane, and fenitrothion. Additionally, correlation analysis demonstrated cross-resistance between bendiocarb and propoxur, and malathion and propoxur. In conclusion, this study has disclosed that pyrethroids are still generally effective for Aedes control in Sabah, Malaysia. The susceptibility status of Ae. albopictus against pyrethroids in descending order was cyfluthrin > lambda-cyhalothrin > deltamethrin > etofenprox > permethrin.
Supergranular turbulence in the quiet Sun: Lagrangian coherent structures
Authors: Chian Abraham C-L , Silva Suzana S A , Rempel Erico L , Gošić Milan , Bellot Rubio Luis R , Kusano Kanya , Miranda Rodrigo A , Requerey Iker S
Published: July 2019

The quiet Sun exhibits a wealth of magnetic activities that are fundamental for our understanding of solar magnetism. The magnetic fields in the quiet Sun are observed to evolve coherently, interacting with each other to form prominent structures as they are advected by photospheric flows. The aim of this paper is to study supergranular turbulence by detecting Lagrangian coherent structures (LCS) based on the horizontal velocity fields derived from Hinode intensity images at disc centre of the quiet Sun on 2010 November 2. LCS act as transport barriers and are responsible for attracting/repelling the fluid elements and swirling motions in a finite time. Repelling/attracting LCS are found by computing the forward/backward finite-time Lyapunov exponent (FTLE), and vortices are found by the Lagrangian-averaged vorticity deviation method. We show that the Lagrangian centres and boundaries of supergranular cells are given by the local maximum of the forward and backward FTLE, respectively. The attracting LCS expose the location of the sinks of photospheric flows at supergranular junctions, whereas the repelling LCS interconnect the Lagrangian centres of neighbouring supergranular cells. Lagrangian transport barriers are found within a supergranular cell and from one cell to other cells, which play a key role in the dynamics of internetwork and network magnetic elements. Such barriers favour the formation of vortices in supergranular junctions. In particular, we show that the magnetic field distribution in the quiet Sun is determined by the combined action of attracting/repelling LCS and vortices.
Unmodelled clustering methods for gravitational wave populations of compact binary mergers
Authors: Powell Jade , Stevenson Simon , Mandel Ilya , Tiňo Peter
Published: July 2019

The mass and spin distributions of compact binary gravitational-wave sources are currently uncertain due to complicated astrophysics involved in their formation. Multiple sub-populations of compact binaries representing different evolutionary scenarios may be present amongst sources detected by Advanced LIGO and Advanced Virgo. In addition to hierarchical modelling, unmodelled methods can aid in determining the number of sub-populations and their properties. In this paper, we apply Gaussian mixture model clustering to 1000 simulated gravitational-wave compact binary sources from a mixture of five sub-populations. Using both mass and spin as input parameters, we determine how many binary detections are needed to accurately determine the number of sub-populations and their mass and spin distributions. In the most difficult case that we consider, where two sub-populations have identical mass distributions but differ in their spin, which is poorly constrained by gravitational-wave detections, we find that ∼400 detections are needed before we can identify the correct number of sub-populations.
Long-Term Smoking Cessation Outcomes for Sexual Minority Versus Nonminority Smokers in a Large Randomized Controlled Trial of Two Web-Based Interventions
Authors: Heffner Jaimee L , Mull Kristin E , Watson Noreen L , McClure Jennifer B , Bricker Jonathan B
Published: July 2019

Introduction

Despite greater smoking prevalence among sexual minority (SM) individuals relative to non-SM individuals, minimal research has examined whether SM smokers have differential success at quitting, and no prior treatment studies have examined differences within SM subgroups. There is also limited knowledge of the psychosocial characteristics of treatment-seeking SM smokers, which could inform targeted treatments. To address these gaps, we compared treatment outcomes and baseline characteristics for SM and non-SM smokers and for bisexual versus lesbian or gay smokers in a large randomized controlled trial of two web-based cessation treatments.

Methods

Trial participants completed a survey to assess baseline characteristics, including self-identification as either SM (n = 253; lesbian or gay, n = 122; bisexual, n = 131) or non-SM (n = 2384). The primary cessation outcome was complete-case, self-reported 30-day abstinence at 12 months after randomization.

Results

Cessation outcomes did not differ significantly for SM versus non-SM smokers (24% vs. 25%, adjusted OR = 0.91, 95% CI = 0.65 to 1.28) or across SM subgroups (24% for bisexual vs. 23% for lesbian or gay, adjusted OR = 1.01, 95% CI = 0.51 to 2.00), and there were no interactions with treatment group assignment. At baseline, SM smokers differed from non-SM smokers on most demographics, were more likely to screen positive for all mental health conditions assessed, and had greater exposure to other smokers in the home.

Conclusions

Substantial differences in baseline characteristics of SM versus non-SM smokers and bisexual versus lesbian or gay smokers did not translate into differential treatment outcomes. Nonetheless, SM smokers’ willingness or ability to quit smoking could be enhanced by taking their unique psychosocial profile into account when designing targeted interventions.

Implications

The findings of this study, which included the largest sample of SM smokers in a prospective intervention trial to date, support those of a small extant body of literature showing no differences in treatment-assisted cessation outcomes between SM and non-SM smokers. Regardless of their quit rates relative to non-SM smokers, SM smokers’ willingness or ability to quit smoking could potentially be enhanced by taking their unique psychosocial profile into account in intervention design, including their younger age, lower socioeconomic status, greater likelihood of being racial or ethnic minorities, and greater prevalence of mental health symptoms.
Dating and relationship violence victimization and perpetration among 11–16 year olds in Wales: a cross-sectional analysis of the School Health Research Network (SHRN) survey
Authors: Young Honor , Long Sara Jayne , Melendez-Torres G J , Kim Hyun Sue , Hewitt Gillian , Murphy Simon , Moore Graham F
Published: July 2019

Background

This study examines the prevalence of dating and relationship violence (DRV) victimization, perpetration and joint victimization and perpetration, and associations between DRV and socio-demographic characteristics.

Methods

Cross-sectional self-report data from 74 908 students aged 11–16 from 193 schools across Wales were collected and analysed using generalized estimating equations to examine prevalence and predictors of emotional and physical DRV victimization, perpetration and joint victimization and perpetration.

Results

More girls reported emotional victimization (28%) and perpetration (18%) than boys (20% and 16%, respectively). More girls (8%) than boys (7%) reported physical perpetration. However, boys (17%) reported more physical victimization than girls (12%). Age-related trajectories of DRV victimization and perpetration were stronger in girls than in boys. Students from single or step parent homes, those in care, and certain ethnic minority groups had increased odds of DRV. No association was found between socioeconomic status and DRV.

Conclusions

Age-related trajectories and the lack of social patterning by socioeconomic status point to the value of early, universal interventions, while some evidence of ethnic patterning and family structure-related risk factors suggest areas for further research and targeted interventions. DRV continues to be a major public health problem for which little UK-specific intervention evidence exists.
Loan sharking: changing patterns in, and challenging perceptions of, an abuse of deprivation
Authors: Saunders Patrick
Published: July 2019

Background

Illegal high interest lending or ‘loan sharking’ exploits the vulnerable and has profound negative impacts on individuals and communities. The 2008 UK financial crash and subsequent austerity programme coupled with changes in the consumer credit market have fuelled an increase in predatory lending.

Methods

The study is a descriptive analysis of demographic, financial, health and behavioural data on 753 victims (2011–2017). A review of the causative factors and potential political, economic and public health responses is analysed.

Results

Most victims were female but males were considerably more indebted. Illegal loans are largely taken out for routine living expenses and over 70% of victims reported other serious debts. Victims are disproportionately poor, unemployed and on benefits but fewer than half have had financial or benefits advice. Despite 90% reporting they would not borrow illegally again, 30% had previously done so from the same shark and over half considered them a friend.

Conclusions

The increase in loan sharking has coincided with the withdrawal of traditional sub-prime lenders and local welfare assistance schemes, and the low penetration of Credit Unions in many areas. Conventional perceptions of loan sharks and their relationships with victims are largely incorrect. A range of coordinated financial, political and social interventions is required.
Predictive factors for sustained remission with stratification by myositis-specific autoantibodies in adult polymyositis/dermatomyositis
Authors: Watanabe Eri , Gono Takahisa , Kuwana Masataka , Terai Chihiro
Published: July 2019

Objective

The aim of this study was to clarify predictive factors for sustained remission in adult patients with PM/DM, particularly focusing on stratification by myositis-specific autoantibodies (MSAs).

Methods

A total of 162 adult patients with PM/DM who were followed up for >1 year after diagnosis were retrospectively enrolled. MSAs were evaluated comprehensively in 102 patients whose sera were available. Sustained remission was defined as no evidence of disease activity (active skin rash, active myositis or active interstitial lung disease) for longer than a 6-month continuous period while undergoing myositis therapy or no medication. Clinical data were reviewed in patients’ medical charts

Results

The sustained remission rate for all patients was 58% during the median follow-up period at 4 years. With regard to MSAs, the achievement rate of sustained remission among MSA-negative patients was significantly higher than that for patients with anti-aminoacyl-tRNA synthetase (P = 0.004), anti-melanoma differentiation-associated gene 5 (P = 0.037) or anti-transcriptional intermediary factor 1-γ (P = 0.013) antibodies. MSA-negative status (odds ratio 5.84, P = 0.009) and absence of severe muscle weakness requiring assistance at diagnosis (odds ratio 43.6, P < 0.001) were independent factors associated with sustained remission in multivariate analysis. Cumulative remission rates were significantly higher (P < 0.001) in patients with both the MSA-negative status and absence of severe muscle weakness at diagnosis than the others.

Conclusion

MSA-negative status and the absence of severe muscle weakness requiring assistance at diagnosis are independent predictive factors for sustained remission in adult PM/DM patients.