bluuebunny/crossref_metadata_2025 huggingface dataset:
Embryotoxicity testing of IVF disposables: how do manufacturers test?
Authors: Delaroche L , Oger P , Genauzeau E , Meicler P , Lamazou F , Dupont C , Humaidan P
Published: December 2019

STUDY QUESTION

How do manufacturers perform embryotoxicity testing in their quality control programs when validating IVF consumables?

SUMMARY ANSWER

The Mouse Embryo Assay (MEA) and Human Sperm Survival Assay (HSSA) used for IVF disposables differed from one manufacturer to another.

WHAT IS KNOWN ALREADY

Many components used in IVF laboratories, such as culture media and disposable consumables, may negatively impact human embryonic development.

STUDY DESIGN, SIZE, DURATION

Through a questionnaire-based survey, the main manufacturers of IVF disposable devices were contacted during the period November to December 2018 to compare the methodology of the MEA and HSSA. We focused on catheters for embryo transfer, catheters for insemination, straws, serological pipettes, culture dishes and puncture needles used in the ART procedures.

PARTICIPANTS/MATERIALS, SETTING, METHODS

We approached the manufacturers of IVF disposables and asked for details about methodology of the MEA and HSSA performed for toxicity testing of their IVF disposable devices. All specific parameters like mouse strains, number of embryos used, culture conditions (media, temperature, atmosphere), extraction protocol, subcontracting, and thresholds were registered and compared between companies.

MAIN RESULTS AND THE ROLE OF CHANCE

Twenty-one companies were approached, of which only 11 answered the questionnaire. Significant differences existed in the methodologies and thresholds of the MEA and HSSA used for toxicity testing of IVF disposables. Importantly, some of these parameters could influence the sensitivity of the tests.

LIMITATIONS, REASONS FOR CAUTION

Although we approached the main IVF manufacturers, the response rate was relatively low.

WIDER IMPLICATIONS OF THE FINDINGS

Our study confirms the high degree of heterogeneity of the embryotoxicity tests performed by manufacturers when validating their IVF disposable devices. Currently, no regulations exist on this issue. Professionals should call for and request standardization and a future higher degree of transparency as regards embryotoxicity testing from supplying companies; moreover, companies should be urged to provide the users clear and precise information about the results of their tests and how testing was performed. Future recommendations are urgently awaited to improve the sensitivity and reproducibility of embryotoxicity assays over time.

STUDY FUNDING/COMPETING INTEREST(S)

This study did not receive any funding. L.D. declares a competing interest with Patrick Choay SAS.

TRIAL REGISTRATION NUMBER

N/A
Human Immunodeficiency Virus (HIV)–Infected CCR6+ Rectal CD4+ T Cells and HIV Persistence On Antiretroviral Therapy
Authors: Anderson Jenny L , Khoury Gabriela , Fromentin Rémi , Solomon Ajantha , Chomont Nicolas , Sinclair Elizabeth , Milush Jeffrey M , Hartogensis Wendy , Bacchetti Peter , Roche Michael , Tumpach Carolin , Gartner Matthew , Pitman Matthew C , Epling Christine Lorrie , Hoh Rebecca , Hecht Frederick M , Somsouk Ma , Cameron Paul U , Deeks Steven G , Lewin Sharon R
Published: December 2019

Background

Identifying where human immunodeficiency virus (HIV) persists in people living with HIV and receiving antiretroviral therapy is critical to develop cure strategies. We assessed the relationship of HIV persistence to expression of chemokine receptors and their chemokines in blood (n = 48) and in rectal (n = 20) and lymph node (LN; n = 8) tissue collected from people living with HIV who were receiving suppressive antiretroviral therapy.

Methods

Cell-associated integrated HIV DNA, unspliced HIV RNA, and chemokine messenger RNA were quantified by quantitative polymerase chain reaction. Chemokine receptor expression on CD4+ T cells was determined using flow cytometry.

Results

Integrated HIV DNA levels in CD4+ T cells, CCR6+CXCR3+ memory CD4+ T-cell frequency, and CCL20 expression (ligand for CCR6) were highest in rectal tissue, where HIV-infected CCR6+ T cells accounted for nearly all infected cells (median, 89.7%). Conversely in LN tissue, CCR6+ T cells were infrequent, and there was a statistically significant association of cell-associated HIV DNA and RNA with CCL19, CCL21, and CXCL13 chemokines.

Conclusions

HIV-infected CCR6+ CD4+ T cells accounted for the majority of infected cells in rectal tissue. The different relationships between HIV persistence and T-cell subsets and chemokines in rectal and LN tissue suggest that different tissue-specific strategies may be required to eliminate HIV persistence and that assessment of biomarkers for HIV persistence may not be generalizable between blood and other tissues.
Forest Management for Carbon Sequestration and Climate Adaptation
Authors: Ontl Todd A , Janowiak Maria K , Swanston Christopher W , Daley Jad , Handler Stephen , Cornett Meredith , Hagenbuch Steve , Handrick Cathy , Mccarthy Liza , Patch Nancy
Published: December 2019

The importance of forests for sequestering carbon has created widespread interest among land managers for identifying actions that maintain or enhance carbon storage in forests. Managing for forest carbon under changing climatic conditions underscores a need for resources that help identify adaptation actions that align with carbon management. We developed the Forest Carbon Management Menu to help translate broad carbon management concepts into actionable tactics that help managers reduce risk from expected climate impacts in order to meet desired management goals. We describe examples of real-world forest-management planning projects that integrate climate change information with this resource to identify actions that simultaneously benefit forest carbon along with other project goals. These examples highlight that the inclusion of information on climate vulnerability, considering the implications of management actions over extended timescales, and identifying co-benefits for other management goals can reveal important synergies in managing for carbon and climate adaptation.
An Explanation of the Veridical Uniformity Universal
Authors: Steinert-Threlkeld Shane
Published: December 2019

A semantic universal, which we here dub the Veridical Uniformity Universal, has recently been argued to hold of responsive verbs (those that take both declarative and interrogative complements). This paper offers a preliminary explanation of this universal: verbs satisfying it are easier to learn than those that do not. This claim is supported by a computational experiment using artificial neural networks, mirroring a recent proposal for explaining semantic universals of quantifiers. This preliminary study opens up many avenues for future work on explaining semantic universals more generally, which are discussed in the conclusion.
PARP inhibitor olaparib sensitizes esophageal carcinoma cells to fractionated proton irradiation
Authors: Kageyama Shun-ichiro , Junyan Du , Hojo Hidehiro , Motegi Atsushi , Nakamura Masaki , Tsuchihara Katsuya , Akimoto Tetsuo
Published: December 2019

Proton beam therapy (PBT) combined with chemotherapy, such as cis-diamminedichloroplatinum (II) (CDDP) and 5-fluorouracil (5-FU), has been employed as an alternative approach to improve clinical outcomes. PBT has been reported to be effective against esophageal cancer. However, apart from 5-FU and CDDP, almost no other drug has been tested in combined chemotherapy with PBT. Therefore, we investigated the effects of a poly (ADP-ribose) polymerase inhibitor on enhancing proton beam effects using esophageal cancer cell lines that exhibit resistance to radiation and CDDP. Esophageal squamous cell carcinoma cell lines OE-21 and KYSE-450 were exposed to the drugs for 1 h prior to irradiation. The cell survival curve was obtained using a clonogenic assay and the sensitizing effect ratio (SER) was calculated. The clonogenic assay was used to compare the effect of multi-fractioned irradiation between 8 Gy/1 fraction (fr) and 8 Gy/4 fr. γH2AX, Rad51, BRCA1, BRCA2 and 53BP1 foci were detected via immunofluorescence. Olaparib exhibited an SER of 1.5–1.7 on PBT. The same sensitizing effect was exhibited in multi-fractioned irradiation, and the combined use increased the expression of double-strand breaks and homologous recombination-related genes in an additive manner. Such additive effects were not observed on non-homologous end joining-related genes. We demonstrated that olaparib has a high sensitizing effect on PBT in platinum- and radiation-resistant esophageal cancer cells. Our results suggest a potential clinical application of olaparib-proton irradiation (PT) against platinum- and radiation-resistant esophageal cancer.
Retromastoid osteoma—a rare case report
Authors: Tan Edmund Wooi Keat , Barco Jason Bae , Rehman Mutee Ur , Tan Choon Chieh
Published: December 2019

Osteomas are slow growing bone tumours and are often asymptomatic. Rarely, they can be present in the temporal bone—only few cases had been reported, with an incidence of 0.1–1%. We describe a case of an osteoma of the temporal bone (retromastoid) found in a 40 year old female, who presented with a slow growing swelling behind the right ear for 9 years. Diagnosis was made on non-contrast computed topography (CT) of the skull. Treatment is indicated in symptomatic cases or cosmetic reasons. Screening colonoscopy and genetic testing for familial adenomatous polyposis (FAP) and Gardner’s syndrome are advised.
Subdural Empyema in an Immunocompetent Active Duty Soldier: A Case Report
Authors: Bridwell Rachel E , Larson Neil P , Yoo Michael J , Oliver Joshua J
Published: December 2019

Intracranial subdural empyema is a rare clinical entity with incidence estimates of 0.1 per 100,000 people. The condition is most often the sequela of a primary infection elsewhere and carries a high morbidity and mortality. The authors present the case of a 22-year-old active duty soldier on mission on the southern border of the United States. The patient had been complaining of headaches that became progressively worse over 2 weeks and presented to a civilian hospital where he was diagnosed with intracranial abscess versus sinus thrombosis on radiographic imaging. The patient was promptly transferred to a military tertiary care center where further workup including pivotal imaging confirmed subdural empyema and right transverse sinus thrombosis. Given the rapid patient deterioration associated with subdural empyema, the emergent intravenous antibiotics, neurosurgical consultation, and subsequent collection evacuation performed are likely to credit for saving this soldier’s life. This case highlighted an atypical and time-sensitive etiology for a common complaint in the active duty population, which underscores the requirement for evacuation to higher roles of care in those soldiers with a similar diagnosis.
SuperNNova: an open-source framework for Bayesian, neural network-based supernova classification
Authors: Möller A , de Boissière T
Published: December 2019

We introduce SuperNNova, an open-source supernova photometric classification framework that leverages recent advances in deep neural networks. Our core algorithm is a recurrent neural network (RNN) that is trained to classify light curves using only photometric information. Additional information such as host-galaxy redshift can be incorporated to improve performance. We evaluate our framework using realistic supernova simulations that include survey detection. We show that our method, for the type Ia versus non-Ia supernova classification problem, reaches accuracies greater than 96.92 ± 0.09 without any redshift information and up to 99.55 ± 0.06 when redshift, either photometric or spectroscopic, is available. Further, we show that our method attains unprecedented performance for the classification of incomplete light curves, reaching accuracies >86.4 ± 0.1 (>93.5 ± 0.8) without host-galaxy redshift (with redshift information) 2 d before maximum light. In contrast with previous methods, there is no need for time-consuming feature engineering and we show that our method scales to very large data sets with a modest computing budget. In addition, we investigate often neglected pitfalls of machine learning algorithms. We show that commonly used algorithms suffer from poor calibration and overconfidence on out-of-distribution samples when applied to supernova data. We devise extensive tests to estimate the robustness of classifiers and cast the learning procedure under a Bayesian light, demonstrating a much better handling of uncertainties. We study the benefits of Bayesian RNNs for SN Ia cosmology. Our code is open sourced and available on github1.
From massive spirals to dwarf irregulars: a new set of tight scaling relations for cold gas and stars driven by disc gravitational instability
Authors: Romeo Alessandro B
Published: December 2019

We present a new set of galaxy scaling relations for the relative mass content of atomic gas, molecular gas, and stars. Such relations are driven by disc gravitational instability, and originate from the low galaxy-to-galaxy variance of Toomre’s Q stability parameter. We test such relations using more than 100 galaxies, from massive spirals to dwarf irregulars, thus spanning several orders of magnitude in stellar mass ($M_{\star }\approx 10^{6\rm {-}11}\, \mbox{M}_{\odot }$) and atomic gas mass ($M_{\rm{H\, \small {I}}}\approx 10^{7\rm {-}10.5}\, \mbox{M}_{\odot }$). Such tests demonstrate (i) that our scaling relations are physically motivated and tightly constrained, (ii) that the mass-averaged gravitational instability properties of galaxy discs are remarkably uniform across the sequence Sa–dIrr, and (iii) that specific angular momentum plays an important role in such a scenario. Besides providing new insights into a very important topic in galaxy evolution, this work provides a simple formula (equation 5) that one can use for generating other galaxy relations driven by disc instability. We explain how to do that, mention a few possible applications, and stress the importance of testing our approach further.
The effects of unresolved double degenerates in the white dwarf luminosity function
Authors: Rebassa-Mansergas A , Toonen S , Torres S , Canals P
Published: December 2019

We perform an analysis of the single white dwarf and the double degenerate binary populations in the solar neighbourhood following a population synthesis approach to investigate the effects of unresolved double degenerates in the white dwarf luminosity function. We consider all unresolved synthetic binaries to be associated with fictitious effective temperatures and surface gravities that are obtained in the same way as if these objects were observed as single point sources. We evaluate the effects of unresolved double white dwarfs assuming that the synthetic samples are ‘observed’ both by the magnitude-limited SDSS and volume-limited Gaia surveys, the latter limited to a distance of no more than 100 pc. We find that, for our standard model, the impact of unresolved double degenerates in the white dwarf luminosity function derived from the Gaia sample is nearly negligible. Unresolved double degenerates are hence expected to have no effect on the age of the Galactic disc, nor on the star formation history from this population. However, for the SDSS sample, the effect of unresolved double degenerates is significant at the brighter bins (Mbol < 6.5 mag), with the fraction of such systems reaching ≃40 per cent of the total white dwarf population at Mbol = 6 mag. This indicates unresolved double degenerates may influence the constraints on the star formation history derived from the SDSS white dwarf sample.
A novel approach to the computation of one-loop three- and four-point functions. II. The complex mass case
Authors: Guillet J Ph. , Pilon E , Shimizu Y , Zidi M S
Published: December 2019

This article is the second of a series of three presenting an alternative method to compute the one-loop scalar integrals, which directly proceeds in terms of the quantities driving the algebraic reduction. The method presented in the first article extends to general complex masses in a systematic way with a few slight adjustments required by the fact that the imaginary parts of these quantities are no longer driven by the Feynman prescription of the propagators but by intricate combinations of imaginary masses, which results in different cases sharing a common structure. As in the case of real masses, it incorporates configurations of kinematics that are more general than those pertaining to physical processes.
Trustees in insolvency: the manifestation of Australia’s fascination with the use of the trust as a business vehicle
Authors: Morrison David
Published: December 2019

Corporate trustees are prevalent in the operation of businesses in Australia. However, the Corporations Act in Australia makes no express provision for the insolvency of a corporate trustee. Given that the trading trust is often used for commercial purposes in Australia, together with a corporate trustee, it is important that the law reflects a clear and consistent approach in the event of the insolvency of a business owned by a trading trust. It is opined that the position of an insolvent corporate trustee ought to be, as far as possible, dealt with consistently with that of a business held directly by a company. Notwithstanding the recommendations of a 1988 inquiry reporting looming difficulty, no legislative correction has occurred. Consequently, a series of conflicting case law follows. This article considers recent developments in respect of judicial consideration in the context of the recommendations made more than 30 years previously.
BHBA treatment improves cognitive function by targeting pleiotropic mechanisms in transgenic mouse model of Alzheimer's disease
Authors: Wu Yancheng , Gong Yuhong , Luan Yongxin , Li Yang , Liu Juxiong , Yue Zitong , Yuan Boyu , Sun Jingxuan , Xie Changxin , Li Lijuan , Zhen Junli , Jin Xinxin , Zheng Yan , Wang Xiaomin , Xie Liwei , Wang Wei
Published: December 2019

Accumulation of amyloid β (Aβ) peptide, inflammation, and oxidative stress contribute to Alzheimer's disease (AD) and trigger complex pathogenesis. The ketone body β‐hydroxybutyrate (BHBA) is an endogenous metabolic intermediate that protects against stroke and neurodegenerative diseases, but the underlying mechanisms are unclear. The present study aims to elucidate the protective effects of BHBA in the early stage of AD model and investigate the underlying molecular mechanisms. Three‐and‐half‐month‐old double‐transgenic mice (5XFAD) overexpressing β‐amyloid precursor protein (APP) and presenilin‐1 (PS1) were used as the AD model. The 5XFAD mice received 1.5 mmol/kg/d BHBA subcutaneously for 28 days. Morris water maze test, nest construction, and passive avoidance experiments were performed to assess the therapeutic effects on AD prevention in vivo, and brain pathology of 5XFAD mice including amyloid plaque deposition and microglia activation were assessed. Gene expression profiles in the cortexes of 5XFAD‐ and BHBA‐treated 5XFAD mice were performed with high‐throughput sequencing and bioinformatic analysis. Mouse HT22 cells were treated with 2 mM BHBA to explore its in vitro protective effects of BHBA on hippocampal neurons against Aβ oligomer toxicity, ATP production, ROS generation, and mitochondrial aerobic respiratory function. APP, BACE1, and neprilysin (NEP) expression levels were evaluated in HT22 cells following treatment with BHBA by measuring the presence or absence of G protein‐coupled receptor 109A (GPR109A). BHBA improved cognitive function of 5XFAD mice in Morris water maze test, nesting construction and passive avoidance experiments, and attenuated Aβ accumulation and microglia overactivation in the brain. BHBA also enhanced mitochondrial respiratory function of hippocampal neurons and protected it from Aβ toxicity. The enzymes, APP and NEP were regulated by BHBA via G‐protein‐coupled receptor 109A (GPR109A). Furthermore, RNA sequencing revealed that BHBA‐regulated genes mainly annotated in aging, immune system, nervous system, and neurodegenerative diseases. Our data suggested that BHBA confers protection against the AD‐like pathological events in the AD mouse model by targeting multiple aspects of AD and it may become a promising candidate for the prevention and treatment of AD.
14 Years Later: A Follow-Up Case-Study Analysis of 8 Health Professions Education Scholarship Units
Authors: Humphrey-Murto Susan , O’Brien Bridget , Irby David M. , van der Vleuten Cees , ten Cate Olle , Durning Steven , Gruppen Larry , Hamstra Stanley J. , Hu Wendy , Varpio Lara
Published: December 2019

Purpose

Internationally, health professions education scholarship units (HPESUs) are often developed to promote engagement in educational scholarship, yet little is known about how HPESUs change over time or what factors support their longevity. In hopes of helping HPESUs thrive, this study explored factors that shaped the evolution of 8 HPESUs over the past 14 years.

Method

This study involved retrospective case-study analysis of the 8 American, Canadian, and Dutch HPESUs profiled in a 2004 publication. First, the research team summarized key elements of HPESUs from the 2004 articles, then conducted semistructured interviews with the current unit directors. In the first set of questions, directors were asked to reflect on how the unit had changed over time, what successes the unit enjoyed, what enabled these successes, what challenges the unit encountered, and how these challenges were managed. In the second set of questions, questions were tailored to each unit, following up on unique elements from the original article. The team used Braun and Clarke’s 6-phase approach to thematic analysis to identify, analyze, and report themes.

Results

The histories of the units varied widely—some had grown by following their original mandates, some had significant mission shifts, and others had nearly disappeared. Current HPESU directors identified 3 key factors that shaped their HPESU’s longitudinal development: the people working within and overseeing the HPESU (the need for a critical mass of scholars, a pipeline for developing scholars, and effective leadership), institutional structures (issues of centralization, unit priorities, and clear messaging), and funding (the need for multiple funding sources).

Conclusions

Study findings offer insights that may help current HPESU directors to strategically plan for their unit’s continued development. Tactically harnessing the factors identified could help directors ensure their HPESU’s growth and contend with the challenges that threaten the unit’s success.
Sleep Moderating the Relationship Between Pain and Health Care Use in Youth With Sickle Cell Disease
Authors: Valrie Cecelia R. , Alston Kristen , Fuh Beng , Redding-Lallinger Rupa , Sisler India
Published: December 2019

Objectives:

The purpose of the current study was to investigate the influence of sleep on the relationship between pain and health care use (HCU) in youth with sickle cell disease (SCD). It was hypothesized that poor sleep would be related to higher HCU and would strengthen the relationship between high pain frequency and more HCU among youth with SCD.

Materials and Methods:

Ninety-six youth with SCD (aged 8 to 17 y) and their guardians were recruited from 3 regional pediatric SCD clinics. Guardians reported on the youth’s pain frequency and HCU using the Structured Pain Interview for parents, and youth wore a sleep actigraph for up to 2 weeks to assess sleep duration and sleep efficiency. A series of regression models were calculated with the following outcomes: emergency department visits, hospitalizations, and health care provider contacts.

Results:

Inconsistent with hypotheses, poor sleep was not directly related to HCU. Also, higher sleep duration appeared to strengthen the relationship between high pain frequency and more emergency department visits.

Conclusions:

Findings suggest that good sleep may serve as a protective factor for better matching pain to HCU. Results should be interpreted in the context of study limitations. Research is needed to investigate possible mechanisms linking sleep duration to HCU in response to pain and to ascertain if sleep patterns influence the relationship between pain and other functional outcomes in youth with SCD. Clinically, these findings support the need to acknowledge and address the role that sleep plays in responding to SCD pain in pediatric populations.
Cosyntropin for the Treatment of Refractory Postdural Puncture Headache in Pediatric Patients
Authors: Zapapas Michelle K. , Gralla Jane , Tong Suhong , Eisdorfer Seth
Published: December 2019

Objectives:

Postdural puncture headache is a challenging complication of diagnostic, therapeutic, and unintentional lumbar puncture. Literature evidence supports cosyntropin as a viable noninvasive therapy for adults who have failed conservative management, but pediatric data are limited. The purpose of this retrospective chart review was to describe the use of intravenous cosyntropin for refractory pediatric postdural puncture headache at a single free-standing tertiary care pediatric hospital.

Methods:

Patients who had received cosyntropin were identified. Charts were retrospectively reviewed for indication, dosing information, efficacy, and side effects. The response was defined as a 50% reduction in pain score, with a secondary efficacy measure of time to discharge after the first dose.

Results:

Over a 5-year period, 26 patients received 37 doses of cosyntropin. Dosing ranged from 5 to 15 mcg/kg (median, 10.4 mcg/kg). There was a significant reduction in pain scores after the first dose of cosyntropin (P=0.008). Eighty-one percent of patients (n=21) achieved either a 50% reduction in pain or were discharged within 24 hours after the first dose. The median time to 50% pain reduction in 13 patients who achieved it before or discharge was 5 hours (range, 1 to 30 h). The median time to discharge after the first dose was 20 hours (range, 2 to 72 h). Ten patients received >1 dose of cosyntropin. Three patients required an epidural blood patch. No adverse effects related to treatment were identified.

Discussion:

This study suggests that while further research is warranted, cosyntropin is a potential alternative to epidural blood patch for pediatric patients with postdural puncture headache who fail conservative management.
Cannabis Use Disorder and Perioperative Outcomes in Major Elective Surgeries
Authors: Goel Akash , McGuinness Brandon , Jivraj Naheed K. , Wijeysundera Duminda N. , Mittleman Murray A. , Bateman Brian T. , Clarke Hance , Kotra Lakshmi P. , Ladha Karim S.
Published: December 2019

Background

Although cannabis is known to have cardiovascular and psychoactive effects, the implications of its use before surgery are currently unknown. The objective of the present study was to determine whether patients with an active cannabis use disorder have an elevated risk of postoperative complications.

Methods

The authors conducted a retrospective population-based cohort study of patients undergoing elective surgery in the United States using the Nationwide Inpatient Sample from 2006 to 2015. A sample of 4,186,622 inpatients 18 to 65 yr of age presenting for 1 of 11 elective surgeries including total knee replacement, total hip replacement, coronary artery bypass graft, caesarian section, cholecystectomy, colectomy, hysterectomy, breast surgery, hernia repair, laminectomy, and other spine surgeries was selected. The principal exposure was an active cannabis use disorder, as defined by International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) diagnostic codes for cannabis dependence and cannabis abuse. The primary outcome was a composite endpoint of in-hospital postoperative myocardial infarction, stroke, sepsis, deep vein thrombosis, pulmonary embolus, acute kidney injury requiring dialysis, respiratory failure, and in-hospital mortality. Secondary outcomes included hospital length of stay, total hospital costs, and the individual components of the composite endpoint.

Results

The propensity-score matched-pairs cohort consisted of 27,206 patients. There was no statistically significant difference between patients with (400 of 13,603; 2.9%) and without (415 of 13,603; 3.1%) a reported active cannabis use disorder with regard to the composite perioperative outcome (unadjusted odds ratio = 1.29; 95% CI, 1.17 to 1.42; P < 0.001; Adjusted odds ratio = 0.97; 95% CI, 0.84 to 1.11; P = 0.63). However, the adjusted odds of postoperative myocardial infarction was 1.88 (95% CI, 1.31 to 2.69; P < 0.001) times higher for patients with a reported active cannabis use disorder (89 of 13,603; 0.7%) compared with those without (46 of 13,603; 0.3%) an active cannabis use disorder (unadjusted odds ratio = 2.88; 95% CI, 2.34 to 3.55; P < 0.001).

Conclusions

An active cannabis use disorder is associated with an increased perioperative risk of myocardial infarction.

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Quantitative proteomic analysis reveals that Luks-PV exerts antitumor activity by regulating the key proteins and metabolic pathways in HepG2 cells
Authors: Zhao Chang-Cheng , Yu Wen-Wei , Qi Ying-Jie , Xu Liang-Fei , Wang Zi-Ran , Qiang Ya-Wen , Ma Fan , Ma Xiao-Ling
Published: December 2019

Hepatocellular carcinoma (HCC) is a complicated and poor prognosis cancer, necessitating the development of a potential treatment strategy. In this study, we initially revealed that LukS-PV belonged to leukocidin family performs an anti-HCC action. Then, we used liquid chromatography-mass spectrometry (LC/MS) to compare protein expression profiles of the LukS-PV-treated human HCC cell lines HepG2 and the control cells. GO annotations and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out of differential expression followed by protein–protein interactome, to explore the underlying cancer suppressor mechanisms of LukS-PV for human HCC. A total of 88 upregulated proteins and 46 downregulated proteins were identified. The top 10 proteins identified by the MCC method are FN1, APP, TIMP1, nucleobindin-1, GOLM1, APLP2, CYR61, CD63, ENG, and CD9. Our observation on protein expression indicated that LukS-PV produces a signature affecting central carbon metabolism in cancer, galactose metabolism, and fructose and mannose metabolism pathways. The results give a functional effects and molecular mechanism insight, following LukS-PV treatment.
Mitochondria and ageing with HIV
Authors: Hunt Matthew , Payne Brendan A.I.
Published: December 2019

Purpose of review

Some older people living with HIV (PLWH) exhibit features of unsuccessful ageing, such as frailty. Mitochondrial dysfunction is one of the best characterized ageing mechanisms. There has been recent interest in whether some people ageing with HIV may have an excess of mitochondrial dysfunction. This review aims to address this question through: analogy with ageing and chronic disease; discussion of the key unknowns; suggested ways that measures of mitochondrial dysfunction might be incorporated into HIV research studies.

Recent findings

Recent data suggest that mitochondrial dysfunction in PLWH may not be wholly a legacy effect of historical nucleoside analog reverse transcriptase inhibitor exposures. Research in the non-HIV setting has altered our understanding of the important mediators of mitochondrial dysfunction in ageing.

Mitochondrial dysfunction is a very plausible driver of adverse ageing phenotypes in some older PLWH. As such it may be a target for therapeutic interventions. Currently, however, there remain considerable uncertainties around the extent of this phenomenon, and its relative importance. Current studies are likely to clarify these questions over the next few years.
Metabolic syndrome, clustering of cardiovascular risk factors and high carotid intima–media thickness in children and adolescents
Authors: Zhao Min , Caserta Carmelo A. , Medeiros Carla C.M. , López-Bermejo Abel , Kollias Anastasios , Zhang Qian , Pacifico Lucia , Reinehr Thomas , Litwin Mieczysław , Bassols Judit , Romeo Elisabetta L. , Ramos Thacira D.A. , Stergiou George S. , Yang Lili , Xargay-Torrent Silvia , Amante Angela , Estrela Tatianne M. , Grammatikos Evangelos , Zhang Yuanyuan , Prats-Puig Anna , Franklin de Carvalho Danielle , Yang Liu , Carreras-Badosa Gemma , de Oliveira Simões Mônica , Hou Yaping , Lizarraga-Mollinedo Esther , Shui Wang , Guo Teng , Wang Mingming , Zhang Yanqing , Bovet Pascal , Xi Bo
Published: December 2019

Objective:

The clinical utility of screening for pediatric metabolic syndrome (MetS) in children and adolescents is still controversial. We examined the performance of pediatric MetS vs. clustering of cardiovascular risk factors (which are the components of MetS) for predicting high carotid intima–media thickness (cIMT) in children and adolescents.

Methods:

Participants included 2427 children and adolescents aged 6–17 years from population-based studies in three countries (Brazil, China and Italy). Pediatric MetS was defined using either the modified National Cholesterol Education Program Adult Treatment Panel III criteria or the modified International Diabetes Federation criteria. Clustering of cardiovascular risk factors was calculated as the sum of five components of MetS (i.e. central obesity, elevated blood pressure, elevated triglycerides, reduced HDL-cholesterol and elevated fasting blood glucose). High cIMT was defined as cIMT at least 95th percentile values for sex and age developed from European children.

Results:

Presence of one, two or at least three cardiovascular risk factors (using the National Cholesterol Education Program Adult Treatment Panel III criteria), as compared with none, was associated with gradually increasing odds of high cIMT [odds ratios (95% confidence intervals): 1.60 (1.29–1.99), 2.89 (2.21–3.78) and 4.24 (2.81–6.39), respectively]. High cIMT was also associated with presence (vs. absence) of MetS (odds ratio = 2.88, 95% confidence interval = 1.95–4.26). However, clustering of cardiovascular risk factors predicted high cIMT markedly better than MetS (area under the curve of 0.66 vs. 0.54, respectively). Findings were similar using the International Diabetes Federation criteria for pediatric MetS.

Conclusion:

In children and adolescents, a graded score based on five cardiovascular risk factors (used to define MetS) predicted high cIMT markedly better than MetS. These findings do not support the clinical utility of MetS for screening youth at increased cardiovascular risk, as expressed in this study by high cIMT.
Urinary sodium-to-potassium ratio and plasma renin and aldosterone concentrations in normotensive children: implications for the interpretation of results
Authors: Martinez-Aguayo Alejandro G. , Campino Carmen , Rodriguez-Fernandez Maria , Poggi Helena , D’apremont Ivonne , Moore Rosario , Garcia Hernan , Solari Sandra , Allende Fidel , Peredo Soledad , Trincado Claudia , Carvajal Cristian , Arancibia Monica , Ossa Jose Tomas , Sifaqui Sofia , Fardella Carlos E. , Baudrand Rene
Published: December 2019

Objectives:

To identify associations among the plasma renin concentration (PRC), plasma aldosterone and urinary sodium (Na)/potassium (K) ratio, and to integrate these variables into a nomogram with the aim of estimating the expected versus observed aldosterone concentration.

Methods:

We studied 40 healthy normotensive children (5–8 years old, 57.5% girls) who were born at term and were adequate for their gestational age. Following overnight fasting, the PRC and plasma aldosterone in blood samples were measured, and the Na/K ratio was calculated from a simultaneously obtained urinary spot sample. A mathematical function was defined with these three variables, and a nomogram was built that would return the expected aldosterone concentration from the obtained plasma renin and urinary Na/K ratio values.

Results:

The PRC (B =  5.9, P < 0.001) and urinary Na/K ratio (B = −98.1, P = 0.003) were significant independent predictors of plasma aldosterone. The correlation between the observed plasma aldosterone and the expected plasma aldosterone, as obtained from the nomogram, was r = 0.88, P < 0.001. The average difference between the observed and expected plasma aldosterone was −0.89, with a standard deviation of ±30%.

Conclusion:

The strong correlation between the urinary Na/K ratio, from urine samples taken at the same as the blood samples, and plasma renin and aldosterone concentrations allowed us to build a nomogram to predict aldosterone levels. This approach may be useful for evaluating the renin–angiotensin–aldosterone system (RAAS) in pediatric patients with hypertension and RAAS dysfunction.
Deposition of Fluorescently Tagged Lysozyme on Contact Lenses in a Physiological Blink Model
Authors: Phan Chau-Minh , Qiao Han , Yee Alan , Jones Lyndon
Published: December 2019

Purpose:

To visualize the deposition of fluorescein isothiocyanate (FITC) lysozyme on daily disposable contact lenses (CLs) using a novel blink model.

Methods:

Three daily disposable conventional hydrogel CLs (etafilcon A, omafilcon A, and nelfilcon A) and three silicone hydrogel CLs (delefilcon A, senofilcon A, and somofilcon A) were evaluated in the study. The CLs were mounted onto a novel blink model and exposed to an artificial tear solution containing FITC lysozyme for 2 and 10 hr. The flow rate and blink speed were set to 1 μL/min and 6 blinks/min, respectively. After the incubation period, a 5-mm-diameter disc was punched out from the center of the lens and mounted on a microscope slide. The slides were imaged using the Zeiss 510 Meta confocal laser scanning microscope, which scanned the lens from the front to the back surface at 5-μm increments.

Results:

There was an increase in deposition of FITC lysozyme for all lens types with increasing incubation time (P<0.05), with the exception of somofilcon A, which did not show statistical significance between 2 and 10 hr (P>0.05). The conventional hydrogel CLs deposited higher amounts of FITC lysozyme than the silicone hydrogel CLs (P<0.001), with etafilcon A depositing the highest at all time points (P<0.05). Interestingly, at the 2-hr incubation time, most CLs showed a higher amount of deposition at the front surface than the back surface of the lens. In particular, etafilcon A showed preferred deposition at the front surface at all time points.

Conclusion:

The results suggest that there is differential deposition at the front surface of the CL, which is exposed to the prelens tear film, compared with the back surface of the CL, which is exposed to the postlens tear film. Therefore, it may be beneficial to design CL materials with differing surface properties for the front and back surfaces of the CL to enhance interactions with the tear film and ocular surface.
Is Arthroscopic Hip Labral Repair/Reconstruction Surgery Effective for Treating Femoroacetabular Impingement in the Presence of Osteoarthritis?
Authors: Nakashima Hirotaka , Utsunomiya Hajime , Kanezaki Shiho , Suzuki Hitoshi , Nakamura Eiichiro , Larson Christopher M. , Sakai Akinori , Uchida Soshi
Published: December 2019

Objective:

To investigate clinical outcomes after arthroscopic labral preservation surgery for femoroacetabular impingement (FAI) in the presence of osteoarthritis (OA) compared with FAI without significant OA.

Design:

Retrospective case–control study.

Setting:

Department of Orthopaedic Surgery and Sports Medicine, Hospital of Academic Institute.

Patients:

Femoroacetabular impingement patients (n = 97; ≥35 years) undergoing arthroscopic FAI correction with labral preservation surgery from March 2009 to April 2014 were enrolled in this study.

Interventions:

Patients were divided into 2 groups: FAI group (79 patients), with Tonnis grade 0 or 1, and FAI + OA group (18 patients), with Tonnis grade 2 or 3.

Main Outcome Measures:

We examined the clinical outcomes using the Modified Harris Hip Score (MHHS), Nonarthritic Hip Score (NAHS), and the conversion rate to total hip arthroplasty (THA).

Results:

No significant differences existed between the 2 groups with respect to age, sex, follow-up period, or preoperative MHHS or NAHS. The mean MHHS and NAHS at the final follow-up were significantly lower in the FAI + OA group than in the FAI group. There was a significant difference in the rate of conversion to THA and failure between the 2 groups (THA 5% vs 50%) (failure 15% vs 67%).

Conclusion:

Patients with FAI in the presence of OA did not improve after arthroscopic labral preservation surgery and had a high conversion rate to THA.

Level of Evidence:

Level III.
Feasibility of a Novel Strategy for Cardiovascular Screening During the Preparticipation Physical Examination
Authors: Dennison Roberta , Kerkhof Deanna L. , Honda Trenton , Calatroni Renato , Corrado Gianmichel D.
Published: December 2019

Objective:

To determine the feasibility of simultaneously conducting history and physical (H&P), limb-lead electrocardiogram (ECG), and preparticipation echocardiography by frontline providers (PEFP) at one screening station.

Methods:

This cross-sectional study compares limb-lead versus 12-lead ECG as part of a preparticipation physical examination (PPE) including H&P and PEFP conducted in year 1 and year 2 on 2 cohorts (n = 36, n = 53, respectively) of college athletes at one institution. Year 1 screening was conducted at 3 stations, one station per screening component. Time to complete each station was recorded, and total time for screening was the summation of times for each station. Year 2 screening was conducted at one station; timing began when the patient entered the room and ended when all 3 components of screening were complete. An unpaired t test was used to compare the mean time difference between years 1 and 2 screening stations.

Results:

Year 1 screening time was significantly longer than time to complete cardiac screening using the year 2 protocol (10.51 ± 1.98 vs 3.96 ± 1.43 minutes, respectively; P < 0.001). Five athletes in year 1 and 3 athletes in year 2 were referred to cardiology for further evaluation; all athletes were ultimately cleared to participate.

Conclusions:

A comprehensive PPE can be completed in a timely fashion using a single screening station and limb-lead ECG to improve efficiency, while still allowing providers to gather information on history, physical examination, heart rhythm, and heart structure. This strategy may serve as a potential solution in the longstanding debate over best practices for PPEs.
The rs72613567
Authors: Di Sessa Anna , Umano Giuseppina Rosaria , Cirillo Grazia , Marzuillo Pierluigi , Arienzo Maria Rosaria , Pedullà Marcella , Miraglia del Giudice Emanuele
Published: December 2019

We first investigated in obese children the protective role of the hydroxysteroid 17‐beta dehydrogenase 13 (HSD17B13) rs72613567:TA variant in liver damage. Six hundred eighty‐five obese children were genotyped for HSD17B13, patatin‐like phospholipase domain containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), and membrane bound O‐acyltransferase domain containing 7 (MBOAT7) polymorphisms and underwent anthropometrical, ultrasonographic, and biochemical evaluation. Indirect measurement of liver fibrosis (Pediatric NAFLD Fibrosis Index [PNFI]) was calculated. The population was clustered in 2 genetic risk groups based on the numbers of steatogenic alleles (low: carriers up to 3 risk alleles, high: 4–6 risk alleles). Carriers of the HSD17B13 rare A allele showed lower percentage of hepatic steatosis and both lower serum transaminase and PNFI levels than noncarriers, even after adjustments for confounders. These findings were also confirmed in both risk groups. We demonstrated the protective effect of the rs72613567:TA HSD17B13 variant in reducing liver damage in obese children regardless of genetic predisposition.
Kawasaki at the Extremes of Age
Authors: Rosario Jennifer M. , Patel Faisalmohemed , Levasseur Kelly , Adams Lauren
Published: December 2019

Kawasaki disease is an acute vasculitis syndrome that typically occurs in children aged 1 to 4 years. Because there is no specific diagnostic test for Kawasaki disease, the diagnosis is made clinically based on specific characteristic signs and symptoms. Cases in which patients fall outside of the typical age range are uncommon and often challenging to diagnose because they have atypical presentations. This is especially true in infants, who rarely meet all the clinical criteria required for diagnosis. Patients at the extremes of ages often have a delayed diagnosis, which can lead to worse cardiac outcomes. We describe the cases of a young infant and an older adolescent who present with Kawasaki disease. These cases illustrate the challenge of diagnosing Kawasaki disease in patients beyond the typical age range. Both patients were return visits to the emergency department after inpatient stays. When fever persists longer than 5 days, clinicians must have a high index of suspicion for Kawasaki disease in all pediatric age groups to prevent treatment delay and disease sequelae.
Beware the Innocent Presentation of a Spontaneous Perforated Meckel Diverticulum
Authors: McKelvie Mark , Soares-Oliveira Miguel , Wang-Koh Yuan , Trayers Claire , Aslam Adil
Published: December 2019

Perforation of a Meckel diverticulum in a preterm neonate is very rare. To our knowledge, only 7 cases of spontaneous Meckel perforation in a preterm neonate have previously been described in the literature. The etiology is uncertain. We present the case of a 30-week preterm female twin with a spontaneous Meckel diverticulum perforation discovered on day 3 of life and review the published cases. A possible etiological explanation for this rare entity at this age group is also suggested.
Effect of 5-Line Signs in the Prediction of Staging, Progression, and Prognosis of Peripheral Lung Carcinoma: Preliminary Observation Report
Authors: Yu Anle , Li Qun , He Jinlong , Zhan Yuefu
Published: December 2019

Background

The single line of the normal interlobar fissure shown on a thin section image can be reconstructed as a 5-line sign on axial maximal intensity projection. The line between the lung nodule and the pleura is called the pleural tail sign on thin image. On the axial maximal intensity projection, it can also be reconstructed as the 5-line sign or fewer than 5 lines.

Objective

This study aimed to observe the effect of 5-line signs in staging, progression, and prognosis of peripheral lung carcinoma.

Materials and Methods

This study included 132 patients with peripheral lung carcinoma. Among these patients, 93 were men and 39 were women, with an age range of 27 to 82 years and a lung nodule range of 0.98 to 8.75 cm. Maximal intensity projection was reconstructed based on 1.0 or 1.25 mm of thin-slice images in multislice spiral computed tomography. Five-line signs on the margin of the nodule (mass) were observed and were classified into grades 1 to 4 according to the sharpness of the 5-line signs.

Results

Multivariate logistic regression analysis showed that the sharpness of the 5-line signs was correlated with N and TNM staging of peripheral lung carcinoma (P = 0.012, P = 0.016). The lower the sharpness of the 5-line signs, the greater the number of cases of progression of the tumor (P < 0.001), and thus the higher the mortality rate and the lower the survival rate (P = 0.001). The sensitivity and specificity of predicting tumor progression were 56.3% and 93.3%, and those of tumor prognosis were 61.1% and 82.4%, respectively.

Conclusions

The sharpness of the 5-line signs has certain effects on the prediction of invasion, progression, and prognosis of lung carcinoma, particularly of small lung cancer (≤3.0 cm).