bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical outcomes and prognosis of non-small-cell lung cancer in patients with chronic lung diseases: a retrospective analysis
Authors: Choi Soohwan , Park Jaekil
Published: February 2020

OBJECTIVES

Lung cancer treatment in patients with chronic lung diseases is challenging because postoperative care is difficult and surgical outcomes are poorer than in patients with healthy lungs. This study aimed to examine postsurgical outcomes of patients with comorbid lung diseases treated for lung cancer.

METHODS

This retrospective study enrolled 1526 patients who underwent curative surgical resection for non-small-cell lung cancer at a single centre between October 2008 and April 2017. Based on computed tomography findings, patients were assigned to 4 groups and their demographic characteristics, clinicopathological features, surgical outcomes and survival were compared.

RESULTS

There were 1101 patients in group A, 266 patients in group B, 62 patients in group C and 97 patients in group D. In the chronic lung disease groups (B, C and D), there was a high percentage of smoking history (86.5%, 79.0% and 92.8%, respectively; P < 0.01). The occurrence rate of postoperative lung complications and operative mortality rates were higher in patients with chronic lung disease. Groups A, B, C and D contained 819 (74.4%), 159 (59.8%), 43 (69.4%) and 65 (67.0%) stage I patients, respectively (P < 0.01). The groups showed significant differences in overall survival and disease-free survival (all P < 0.01). The presence of combined pulmonary fibrosis and emphysema was the only significant negative prognostic factor for overall survival.

CONCLUSIONS

The presence of comorbid chronic lung diseases might negatively affect prognosis in patients with non-small-cell lung cancer. The presence of combined pulmonary fibrosis and emphysema could be a negative prognostic factor in lung cancer treatment.
Pacemaker implantation after aortic valve replacement: rapid-deployment Intuity® compared to conventional bioprostheses
Authors: Herry Morgane , Laghlam Driss , Touboul Olivier , Nguyen Lee S , Estagnasié Philippe , Brusset Alain , Squara Pierre
Published: February 2020

OBJECTIVES

The aim of this study was to compare the incidence of permanent pacemaker (PPM) implantation after aortic valve replacement by rapid-deployment bioprosthesis (RDB) and standard valve (Standard).

METHODS

All patients undergoing aortic valve replacement between 2015 and 2018, in 1 centre, were included. A multivariate analysis on the whole cohort and then a propensity score matching were used to compare the 2 groups. The primary end point was PPM implantation.

RESULTS

We studied 924 patients (256 RDBs and 668 Standards). Overall, 67 PPM were implanted, 37 (14.5%) in the RDB group and 26 (3.9%) in the Standard group (P < 0.0001, univariate analysis). The multivariate analysis in the unmatched population found 4 independent factors associated with PPM implantation: right bundle branch block with odds ratios (ORs 3.7, 95% CI 2.9–6.7; P < 0.0001), RDB (OR 3.6, 95% CI 2.0–6.2; P < 0.0001), age (OR 1.1, 95% CI 1.0–1.1; P < 0.006) and endocarditis (OR 3.4, 95% CI 1.0–11.0; P < 0.04). In the propensity score-matched RDB group (203 patients per group), 25 patients required PPM implantation versus 3 in the Standard group (12.3% vs 1.5%, P < 0.0001). RDBs also had more postoperative left bundle branch block and new onset of atrial fibrillation (30.2% vs 5.1%, P < 0.0001 and 34.0% vs 24.1%, P = 0.029). RDBs had lower operating times (in min): aortic cross-clamping = 62 (44–76.5) vs 72 (57.5–91.5) and cardiopulmonary bypass = 81 (63–98.5) vs 91 (75–112), P < 0.0001. There was no significant difference in other outcomes.

CONCLUSIONS

RDBs were associated with reduced operating times, increased risk of atrial fibrillation and PPM implantation as compared with standard aortic valves.
Volunteer engagement to inform research on cardiovascular health awareness, Canada
Authors: Lussier Marie-Thérèse , Kaczorowski Janusz , Girard Magali , Arpin Emmanuelle
Published: February 2020

Volunteers have been extensively used in health promotion programmes. However, they have been less frequently involved in the research process. In its most recent iterations, the Cardiovascular Health Awareness Program (CHAP) integrated volunteers (i) to facilitate CHAP sessions with participating patients for data collection and (ii) to evaluate the intervention. Drawing on the patient and public involvement literature, our research team included volunteers in the data collection and evaluation of CHAP sessions as part of the programme’s implementation in the province of Quebec (Canada). We sought volunteers’ formal feedback through individual online and phone interviews and through focus groups for each of the four projects conducted in Quebec. We found that volunteers provide valuable insight on the research protocol as well as patient needs. Their feedback led to several modifications to the research protocol and procedures of subsequent CHAP sessions. Changes included involving volunteers at earlier stages of the research process, adding more learning modules and practice sessions during the volunteer training and defining research priorities according to patient needs. Our methodology of engaging volunteers in the research process was useful to gain important and unique insight on patient needs and for future programme planning to modify the research process.
An Extension of Weyl’s Equidistribution Theorem to Generalized Polynomials and Applications
Authors: Bergelson Vitaly , Håland Knutson Inger J , Son Younghwan
Published: February 2020

Generalized polynomials are mappings obtained from the conventional polynomials by the use of the operations of addition and multiplication and taking the integer part. Extending the classical theorem of Weyl on equidistribution of polynomials, we show that a generalized polynomial $q(n)$ has the property that the sequence $(q(n) \lambda )_{n \in \mathbf{Z}}$ is well-distributed $\bmod \, 1$ for all but countably many $\lambda \in{\mathbf R}$ if and only if $\lim\nolimits _{\substack{|n| \rightarrow \infty \\ n \notin J}} |q(n)| = \infty $ for some (possibly empty) set $J$ having zero natural density in $\mathbf{Z}$. We also prove a version of this theorem along the primes (which may be viewed as an extension of classical results of Vinogradov and Rhin). Finally, we utilize these results to obtain new examples of sets of recurrence and van der Corput sets.
Measurement of Total Fructan in Foods by Enzymatic/Spectrophotometric Method: Collaborative Study
Authors: McCleary Barry V , Murphy Ann , Mugford David C ,   Collaborators:, Andersen Rikki , Ashton John , Blakeney Tony , Boorman Julie , Duncan Karen , Farnell Peter , Fulford Abigail , Hermans Marc , King Deanne , Li Betty , McNaught Ken , Mhller Marina , Nuavia Juan , Pontis Horacio , Puebla Andrea , Salelno Grace , Salman Hayfa , Solah Vicky , Srrensen Annemarie , Suter Dai , van Eekelen Jack , van der Waal Wim , Walker Richard , Wo Catherine
Published: February 2020

An AOAC collaborative study was conducted to evaluate the accuracy and reliability of an enzyme assay kit procedure for measuring oligofructans and fructan polysaccharide (inulins) in mixed materials and food products. The sample is extracted with hot water, and an aliquot is treated with a mixture of sucrase (a specific sucrose-degrading enzyme), α-amylase, pullulanase, and maltase to hydrolyze sucrose to glucose and fructose, and starch to glucose. These reducing sugars are then reduced to sugar alcohols by treatment with alkaline borohydride solution. The solution is neutralized, and excess borohydride is removed with dilute acetic acid. The fructan is hydrolyzed to fructose and glucose using a mixture of purified exo- and endo-inulinanases (fructanase mixture). The reducing sugars produced (fructose and glucose) are measured with a spectrophotometer after reaction with para-hydroxybenzoic acid hydrazide. The samples analyzed included pure fructan, chocolate, low-fat spread, milk powder, vitamin tablets, onion powder, Jerusalem artichoke flour, wheat stalks, and a sucrose/cellulose control flour. Repeatability relative standard deviations ranged from 2.3 to 7.3%; reproducibility relative standard deviations ranged from 5.0 to 10.8%.
Liquid Chromatographic Determination of Lysine, Methionine, and Threonine in Pure Amino Acids (Feed Grade) and Premixes: Collaborative Study
Authors: Fontaine Johannes , Eudaimon Marcelle ,   Collaborators:, Bargholz J , Empie M W , Eriksson S , Hoeg T , Katayama M , Kang K-R , Lee H , Legler J , Llames C R , MacDonald J L , Pierre F , Regnier J-M , Schwadorf K , van der Lee R A , Verbeek K
Published: February 2020

A total of 17 laboratories (including one author's laboratory) participated in a collaborative study for determination of lysine, methionine, and threonine in trade products or concentrated amino acid premixes. Thirteen samples, 4 pure amino acids and 6 premixes, including 3 Youden matched pairs, were analyzed. The applied liquid chromatographic (LC) method using cation-exchange resin and post-column derivatization with ninhydrin or o-phthaldialdehyde was shown to be accurate and specific for the analytes. Titration procedures, normally used for the assay of pure amino acids, are unspecific and the accuracy of the results can be affected by impurities. Repeatability relative standard deviations, RSDr, ranged from 0.84 to 1.17% for pure amino acids and from 0.50 to 1.68% for premixes; reproducibility relative standard deviations RSDR, ranged from 1.52 to 2.31% for pure amino acids and from 1.48 to 2.59% for premixes. Recoveries were between 97.5 and 102.8% of the expected amino acid assays. The method has been adopted Official First Action status by AOAC INTERNATIONAL.
Do Ready-Mix Insecticides Cause Lethal and Sublethal Effects on Trichogramma pretiosum (Hymenoptera: Trichogrammatidae) Pupa?
Authors: de Paiva Ana Clara R , Iost Filho Fernando H , Parro Eduardo A , Barbosa Daniel P L , Yamamoto Pedro T
Published: February 2020

The use of selective insecticides aids farmers in maintaining pest populations below the economic threshold level. The integrated use of biological and chemical control is only possible if the effects of insecticides on natural enemies are studied. Although the IOBC/WPRS standards allow us to compare these studies worldwide, the methods used are sometimes inconsistent. This study determined the effects of ready-mix insecticides applied on pupae of Trichogramma pretiosum (Riley, 1879) (Hymenoptera: Trichogrammatidae) and compared the effects on emergence of two different methods of exposing T. pretiosum pupae to insecticides: immersed or sprayed using a Potter tower. Both methods gave the same results, indicating that they can be compared. Moreover, it is important to go beyond IOBC/WPRS classification and study the effects of pesticides on different biological parameters of natural enemies. This additional step may increase the likelihood of successful integration of biological and chemical control. Based on the emergence reduction, Chlorantraniliprole + lambda-cyhalothrin, abamectin + chlorantraniliprole, and alpha-cypermethrin + teflubenzuron were classified as innocuous (class 1). Cypermethrin + profenofos and cyproconazole + thiamethoxam were classified as slightly harmful (class 2). Methanol + methomyl and lufenuron + profenofos were classified as harmful (class 4). Abamectin + chlorantraniliprole, although classified as innocuous, reduced the parasitism, longevity, and flight capability of the adult parasitoids. None of these insecticides altered the emergence and sex ratio of the second generation.
Scent anointing in mammals: functional and motivational insights from giant pandas
Authors: Charlton B D , Owen M A , Zhang H , Swaisgood R R
Published: February 2020

Although several mammals impregnate their fur with environmental odors, a phenomenon termed scent anointing or rubbing, the functional relevance of this behavior often is unclear. One theory is that scent anointing could be a form of scent matching with environmental odors to signal competitiveness and home range occupation. In this study we presented giant pandas with a range of odors to determine whether scent matching could provide a functional explanation for scent anointing in this species. We found that only a musk-based perfume elicited significantly more scent-anointing and scent-marking behavior than control. Males were also significantly more likely to scent-anoint and scent-mark than females. A preference for anointing, but not scent marking, when presented with peppermint (an insecticide) also was revealed. Our results suggest that giant pandas differentially scent-anoint with foreign odors to signal home range occupation, and possibly to repel ectoparasites. We also highlight how chemical signaling of resource-holding potential is likely to play an important role in determining competitive interactions between adult male giant pandas.
Sex Differences in Early Cognitive Development After Prenatal Exposure to Opioids
Authors: Skumlien Martine , Ibsen Inge Olga , Kesmodel Ulrik Schiøler , Nygaard Egil
Published: February 2020

Objective

Prenatal opioid exposure has been linked with impaired cognitive development, with boys potentially at elevated risk. In the present study, we examined cognitive and language development of children prenatally exposed to opioids, with an additional focus on sex differences.

Methods

A sample of 378 children (n = 194 girls and n = 184 boys) aged 1.2–42.8 months was drawn from the Danish Family Outpatient Clinic database. Developmental outcomes were assessed using the Bayley-III cognitive and language scales, and substance exposure was determined with urine screening and/or verbal report. Children exposed to opioids (n = 94) were compared to children with no prenatal substance exposure (n = 38), and children exposed to alcohol (n = 131) or tobacco (n = 115). Group and sex differences were investigated with separate linear mixed models for each Bayley scale, controlling for concurrent cannabis exposure.

Results

There were significantly reduced scores in opioid-exposed boys compared to boys with no prenatal substance exposure, but no difference between opioid-exposed and nonexposed girls. Additionally, alcohol-exposed boys had lower cognitive scores than nonexposed boys, and alcohol-exposed girls had lower scores on both scales compared to opioid-exposed girls. There were otherwise no significant differences according to group, sex, or scale.

Conclusions

The present findings indicate poorer cognitive and language development in boys after prenatal opioid exposure. As academic performance is rooted in cognitive functioning, long-term follow-up might be necessary for exposed children.
Rocking shadows in broken circumbinary discs
Authors: Nealon Rebecca , Price Daniel J , Pinte Christophe
Published: February 2020

We use three-dimensional simulations with coupled hydrodynamics and Monte Carlo radiative transfer to show that shadows cast by the inner disc in broken circumbinary discs move within a confined range of position angles on the outer disc. Over time, shadows appear to rock back and forth in azimuth as the inner disc precesses. The effect occurs because the inner disc precesses around a vector that is not the angular momentum vector of the outer disc. We relate our findings to recent observations of shadows in discs.
Sequence specificity, energetics and mechanism of mismatch recognition by DNA damage sensing protein Rad4/XPC
Authors: Panigrahi Abhinandan , Vemuri Hemanth , Aggarwal Madhur , Pitta Kartheek , Krishnan Marimuthu
Published: February 2020

The ultraviolet (UV) radiation-induced DNA lesions play a causal role in many prevalent genetic skin-related diseases and cancers. The damage sensing protein Rad4/XPC specifically recognizes and repairs these lesions with high fidelity and safeguards genome integrity. Despite considerable progress, the mechanistic details of the mode of action of Rad4/XPC in damage recognition remain obscure. The present study investigates the mechanism, energetics, dynamics, and the molecular basis for the sequence specificity of mismatch recognition by Rad4/XPC. We dissect the following three key molecular events that occur as Rad4/XPC tries to recognize and bind to DNA lesions/mismatches: (a) the association of Rad4/XPC with the damaged/mismatched DNA, (b) the insertion of a lesion-sensing β-hairpin of Rad4/XPC into the damage/mismatch site and (c) the flipping of a pair of nucleotide bases at the damage/mismatch site. Using suitable reaction coordinates, the free energy surfaces for these events are determined using molecular dynamics (MD) and umbrella sampling simulations on three mismatched (CCC/CCC, TTT/TTT and TAT/TAT mismatches) Rad4-DNA complexes. The study identifies the key determinants of the sequence-dependent specificity of Rad4 for the mismatches and explores the ramifications of specificity in the aforementioned events. The results unravel the molecular basis for the high specificity of Rad4 towards CCC/CCC mismatch and lower specificity for the TAT/TAT mismatch. A strong correlation between the depth of β-hairpin insertion into the DNA duplex and the degree of coupling between the hairpin insertion and the flipping of bases is also observed. The interplay of the conformational flexibility of mismatched bases, the depth of β-hairpin insertion, Rad4-DNA association energetics and the Rad4 specificity explored here complement recent experimental FRET studies on Rad4-DNA complexes.
2′-Alkynyl spin-labelling is a minimally perturbing tool for DNA structural analysis
Authors: Hardwick Jack S , Haugland Marius M , El-Sagheer Afaf H , Ptchelkine Denis , Beierlein Frank R , Lane Andrew N , Brown Tom , Lovett Janet E , Anderson Edward A
Published: February 2020

The determination of distances between specific points in nucleic acids is essential to understanding their behaviour at the molecular level. The ability to measure distances of 2–10 nm is particularly important: deformations arising from protein binding commonly fall within this range, but the reliable measurement of such distances for a conformational ensemble remains a significant challenge. Using several techniques, we show that electron paramagnetic resonance (EPR) spectroscopy of oligonucleotides spin-labelled with triazole-appended nitroxides at the 2′ position offers a robust and minimally perturbing tool for obtaining such measurements. For two nitroxides, we present results from EPR spectroscopy, X-ray crystal structures of B-form spin-labelled DNA duplexes, molecular dynamics simulations and nuclear magnetic resonance spectroscopy. These four methods are mutually supportive, and pinpoint the locations of the spin labels on the duplexes. In doing so, this work establishes 2′-alkynyl nitroxide spin-labelling as a minimally perturbing method for probing DNA conformation.
Risk stratification in pediatric low-grade glioma and glioneuronal tumor treated with radiation therapy: an integrated clinicopathologic and molecular analysis
Authors: Acharya Sahaja , Liu Jo-Fen , Tatevossian Ruth G , Chiang Jason , Qaddoumi Ibrahim , Gajjar Amar , Walker David , Harreld Julie H , Merchant Thomas E , Ellison David W
Published: February 2020

Background

Management of unresectable pediatric low-grade glioma and glioneuronal tumor (LGG/LGGNT) is controversial. There are no validated prognostic features to guide use of radiation therapy (RT). Our study aimed to identify negative prognostic features in patients treated with RT using clinicopathologic and molecular data and validate these findings in an external dataset.

Methods

Children with non-metastatic, biopsy-proven unresectable LGG/LGGNT treated with RT at a single institution between 1997 and 2017 were identified. Recursive partitioning analysis (RPA) was used to stratify patients into low- and high-risk prognostic groups based on overall survival (OS). CNS9702 data were used for validation.

Results

One hundred and fifty patients met inclusion criteria. Median follow-up was 11.4 years. RPA yielded low- and high-risk groups with 10-year OS of 95.6% versus 76.4% (95% CI: 88.7%–98.4% vs 59.3%–87.1%, P = 0.003), respectively. These risk groups were validated using CNS9702 dataset (n = 48) (4-year OS: low-risk vs high-risk: 100% vs 64%, P < 0.001). High-risk tumors included diffuse astrocytoma or location within thalamus/midbrain. Low-risk tumors included pilocytic astrocytoma/ganglioglioma located outside of the thalamus/midbrain. In the subgroup with known BRAF status (n = 49), risk stratification remained prognostic independently of BRAF alteration (V600E or fusion). Within the high-risk group, delayed RT, defined as RT after at least one line of chemotherapy, was associated with a further decrement in overall survival (P = 0.021).

Conclusion

A high-risk subgroup of patients, defined by diffuse astrocytoma histology or midbrain/thalamus tumor location, have suboptimal long-term survival and might benefit from timely use of RT. These results require validation.
AN EXTENSION OF THE BOURGAIN–SARNAK–ZIEGLER THEOREM WITH MODULAR APPLICATIONS
Authors: Cafferata M , Perelli A , Zaccagnini A
Published: February 2020

We first prove an extension of the Bourgain–Sarnak–Ziegler theorem, relaxing some conditions and giving quantitative estimates. Then we apply our extension to bound certain exponential sums, where the coefficients come from modular forms and the exponential involves polynomial sequences of any degree.
GRADIENT AND HESSIAN ESTIMATES FOR DIRICHLET AND NEUMANN EIGENFUNCTIONS
Authors: Wang Feng-Yu
Published: February 2020

We establish integral formulas and sharp two-sided bounds for the Ricci curvature, mean curvature and second fundamental form on a Riemannian manifold with boundary. As applications, sharp gradient and Hessian estimates are derived for the Dirichlet and Neumann eigenfunctions.
Joint trajectories of disease activity, and physical and mental health-related quality of life in an inception lupus cohort
Authors: Fung William , Lim Lily Siok Hoon , Tomlinson George , Engel Lisa , Su Jiandong , Diaz-Martinez Juan Pablo , Touma Zahi
Published: February 2020

Objectives

To examine for latent patterns of SLE disease activity trajectories that associate with specific latent patterns of health-related quality of life (HRQoL; Medical Outcomes Study Short Form-36), and to determine baseline predictors of class membership.

Methods

In this retrospective longitudinal inception cohort of 222 SLE adults over 10 years, trajectories of three outcomes were studied jointly: Short Form-36 physical (PCS) and mental (MCS) component summaries and adjusted mean SLEDAI-2000 (AMS). Group-based joint trajectory modelling was used to model latent classes; univariable and multivariable analyses were used to identify predictors of class membership.

Results

Four latent classes were identified: Class 1 (C1) (24%) had moderate AMS, and persistently low PCS and MCS; C2 (26%) had low AMS, moderate PCS and improved then worsened MCS; C3 (38%) had moderate AMS, and persistently high PCS and MCS; and C4 (11%) had high AMS, moderate-low PCS and improving MCS. Baseline older age was associated with lower HRQoL trajectories. Higher AMS trajectories did not associate with a particular pattern of HRQoL trajectory. A higher prevalence of fibromyalgia (44% in C1) was associated with worse HRQoL trajectories. Disease manifestations, organ damage and cumulative glucocorticoid were not differentially distributed across the latent classes.

Conclusion

High disease activity did not necessarily associate with low HRQoL. More patients with worse HRQoL trajectories had fibromyalgia. Older age at diagnosis increased the probability of belonging to a class with low HRQoL trajectories. The care of SLE patients may be improved through addressing fibromyalgia in addition to disease activity.
Introducing the First European Symposium on the Evolution of Crocodylomorpha
Authors: Puértolas-Pascual Eduardo , Young Mark T , Brochu Christopher A
Published: February 2020

The First European Symposium on the Evolution of Crocodylomorpha took place during the XVI Annual Meeting of the European Association of Vertebrate Palaeontologists (EAVP) organized by NOVA University of Lisbon (UNL) in Caparica, Portugal. Fourteen lectures and five posters were presented at the symposium in June 26th–July 1st, 2018. This special issue showcases twelve papers based on symposium contributions.
A new species of deropristid trematode from the sterlet Acipenser ruthenus (Actinopterygii: Acipenseridae) and revision of superfamily affiliation of the family Deropristidae
Authors: Sokolov Sergey , Voropaeva Ekaterina , Atopkin Dmitry
Published: February 2020

A new species, Skrjabinopsolus nudidorsalis sp. nov. is described from the sterlet Acipenser ruthenus, caught in the River Volga basin (Russia). This species differs from previously described congeners by the absence of vitelline follicles on the dorsal side of the body. The complete 18S rRNA and partial 28S rRNA gene sequences obtained for S. nudidorsalis are the first molecular data for the family Deropristidae. The results of phylogenetic analysis indicate that Deropristidae is sister to the Monorchiidae + Lissorchiidae group. The results of the phylogenetic study contradict the current taxonomic hypothesis that Deropristidae belongs to the superfamily Lepocreadioidea and allow inclusion of this family in Monorchioidea. The morphological similarity of deropristids to other monorchioids is recognizable from the presence of a bipartite internal seminal vesicle, spinous cirrus and a voluminous, armed metraterm.
Managing challenging behaviors in patients with dementia
Authors: Julian Marcia K. , Duran Jackie
Published: February 2020

As nurses, we can impact our patients' and their caregivers' quality of life by providing innovative options for dementia care.
The Parental Experience of Newborns With Neonatal Abstinence Syndrome Across Inpatient Care Settings: A Qualitative Study
Authors: Buczkowski Amy , Avidan Olivia , Cox David , Craig Alexa
Published: February 2020

Objectives:

Understanding the experience of parents with newborns hospitalized with neonatal abstinence syndrome (NAS) across all inpatient settings is important in optimizing their involvement as part of the care team. A descriptive qualitative study design was utilized to understand the parental experience and identify barriers to parent involvement in care of newborns with NAS care.

Methods:

Semistructured one-on-one interviews were conducted with parents of a convenience sample of fifteen infants admitted for NAS in the newborn nursery and level II/III neonatal intensive care unit within a tertiary care center in Northern New England. Interviews were analyzed using thematic content analysis.

Results:

Sixty percent of mothers were treated with buprenorphine during pregnancy, and 60% of infants required pharmacological treatment for NAS symptoms. The predominant themes of parental experience included preparation/education for hospitalization, communication with providers, NAS management, family resources, physical hospital environment, and maternal guilt.

Conclusion:

The parental experience of care for NAS is negatively affected by lack of standardized NAS education in the prenatal and postnatal settings, inconsistent communication with providers, the Finnegan scoring system, lack of provider sensitivity to parental substance use disorder, and maternal guilt. This study also highlights the parental desire to be more involved in the care of newborns with NAS.
Neural Cell Adhesion Molecule (NCAM) a Serum Biomarker Indicative for the Severity of Cervical Spondylotic Myelopathy
Authors: Akshota Nissim , Friedlander Alon , Hershkovich Oded , Gurevich Michael , Givon Uri , Sakhini Mojahed , Achiron Anat
Published: February 2020

Study Design:

Peripheral blood samples were obtained from 25 patients with cervical spondylotic myelopathy (CSM) and 13 healthy volunteers.

Objectives:

Our aim was to investigate the significance of neurodegenerative biomarkers in patients with CSM and correlate their expression with CSM severity.

Summary of Background Data:

CSM is a common disorder involving chronic progressive compression of the cervical spinal resulting in progressive neurological impairment that ranges from mild tingling in the upper limbs to complete quadriplegia. However, the immunological background related to the neurodegenerative damage and its significance in CSM is still unclear.

Methods:

Protein expression profiles of 14 neurodegenerative biomarkers were measured by multiplex Luminex bead assay and further analyzed by group comparison statistics, correlation studies, and receiver-operating characteristic analysis.

Results:

Eleven of 14 biomarkers were significantly elevated in CSM patients as compared with healthy subjects (P<0.05). Specifically, the clinical severity of CSM on the scales of Nurick and modified Japanese Orthopedics Association scale (mJOA) was inversely related to neural cell adhesion molecule (NCAM) levels (r=−0.529, P=0.007; r=−0.519, P=0.001, respectively).

Conclusions:

Serum level of neural cell adhesion molecule may serve as a diagnostic biomarker correlating with the severity of CSM.
Occurrence and Risk Factors of Chronic Pain After Critical Illness
Authors: Koster-Brouwer Maria E. , Rijsdijk Mienke , van Os Wouter K. M. , Soliman Ivo W. , Slooter Arjen J. C. , de Lange Dylan W. , van Dijk Diederik , Bonten Marc J. M. , Cremer Olaf L.
Published: February 2020

Objectives:

Occurrence, risk factors, and impact on daily life of chronic pain after critical illness have not been systematically studied.

Design:

Cohort study.

Setting:

A tertiary ICU in The Netherlands.

Patients:

We surveyed patients who had been discharged from our ICU between 2013 and 2016. Three cohorts were defined as follows: 1) ICU survivors; 2) one-year survivors reporting newly-acquired chronic pain; and (3) one-year survivors with pain who lived within 50 km from the study hospital. In cohort 1, we estimated the prevalence of new chronic pain 1 year after ICU discharge and constructed a prediction model for its occurrence incorporating three outcomes: death during follow-up, surviving without new pain, and surviving with newly-acquired pain. In cohort 2, we determined clinical features of pain and its impact on daily life. In cohort 3, we assessed the presence of neuropathic characteristics of pain.

Interventions:

None.

Measurements and Main Results:

The three cohorts contained 1,842, 160, and 42 patients, respectively. Estimated occurrence of new chronic pain was 17.7% (95% CI, 15.8–19.8%;n= 242) in 1-year survivors (n= 1,368). Median pain intensity on the numeric rating scale was 4 (interquartile range, 2–6) in the week before survey response, with impact being most evident on activities of daily living, social activities, and mobility. Neuropathic pain features were present in 50% (95% CI, 37–68%) of affected subjects. Among nine predictor variables included in a multinomial model, only female gender and days in ICU with hyperinflammation were associated with pain.

Conclusions:

Newly-acquired chronic pain is a frequent consequence of critical illness, and its impact on daily life of affected patients is substantial.
Morus nigra leaves extract revokes the depressive-like behavior, oxidative stress, and hippocampal damage induced by corticosterone: a pivotal role of the phenolic syringic acid
Authors: Dalmagro Ana Paula , Camargo Anderson , Pedron Natália B. , Garcia Suliana A.M. , Zeni Ana Lúcia B.
Published: February 2020

The pathophysiology of depression includes glucocorticoids excess, glutamatergic excitotoxicity, and oxidative stress impairment. Previous study demonstrated Morus nigra L. leaves extract and syringic acid (4-hydroxy-3,5-dimethoxybenzoic acid), its major phenolic compound, administered orally for 7 days, decreased the immobility time in the tail suspension test, without locomotor alteration. Therefore, the purpose of this study was to investigate the antidepressant-like effects, antioxidant effects, and neuroprotective effects of M. nigra leaves extract and syringic acid in an animal model of depression induced by corticosterone. Herein, corticosterone administered in male Swiss mice, 60–90 days of age, at 20 mg/kg, once a day, for 21 days, was effective to induce depressive-like phenotype. This alteration was accompanied by the increase of oxidative stress markers (lipid peroxidation, nitrite, and protein carbonyl) and the decrease in nonprotein thiols level, besides impairment in the hippocampus. Conversely, the treatment with M. nigra leaves extract (10 mg/kg), syringic acid (1 mg/kg), or fluoxetine (10 mg/kg), administered once a day for the last 7 days of the corticosterone treatment, was able to abolish the behavioral alterations elicited by corticosterone, reinforcing evidence of the M. nigra leaves extract and syringic acid having antidepressant-like effect. Both treatments also exerted antioxidant property in the mice’s brain, reducing the amount of oxidative stress and abolishing the corticosterone-induced damage in the hippocampal slices. In addition, the treatments protected the hippocampus against the damage induced by the association between corticosterone administration and glutamate excess. In conclusion, M. nigra leaves extract and syringic acid revoke depressive-like behavior induced by corticosterone via inhibition of oxidative stress and hippocampal damage.
A Retrospective Analysis of Steady-State Olanzapine Concentrations in Chinese Patients Using Therapeutic Drug Monitoring: Effects of Valproate and Other Factors
Authors: Deng Shu-hua , Wang Zhan-Zhang , Lu Hao-Yang , Li Lu , Hu Jin-Qing , Zhu Xiu-Qing , Xie Huan-Shan , Chen Hong-Zhen , Zhang Ming , Ni Xiao-Jia , Qiu Chang , Shang De-Wei , Wen Yu-Guan
Published: February 2020

Background:

The objective of this study was to investigate the serum concentrations of olanzapine in relation to age, sex, and other factors in Chinese patients aged between 10 and 90 years.

Methods:

Data for 884 olanzapine patients, deposited between 2016 and 2017, were retrieved from the therapeutic drug monitoring database of the Affiliated Brain Hospital of Guangzhou Medical University. The effects of covariates on serum olanzapine concentration, dose-normalized concentration (C/D ratio), and normalized concentration (C/D/weight) were investigated.

Results:

Generally, male patients had lower olanzapine concentration, C/D ratio, and C/D/weight than female patients (P < 0.001). Smoking and drinking reduced olanzapine concentration, C/D ratio, and C/D/weight (P < 0.001). Coadministration with valproate decreased olanzapine concentration, C/D ratio, and C/D/weight by about 16%, 30%, and 40%, respectively (P < 0.001). Patients younger than 60 years had higher olanzapine concentrations (P < 0.05) but lower C/D ratios and C/D/weight (P < 0.001) than patients older than 60 years. Age was correlated with olanzapine concentration (r = −0.082, P < 0.05), C/D ratio (r = 0.196, P < 0.001), and C/D/weight (r = 0.169, P < 0.001). Sample timing after dose and diagnostic factors also contributed to the olanzapine concentrations. Multiple linear regression analysis revealed significant influences of dosage, age, sex, valproate comedication, smoking, postdose interval, and schizophrenia (vs bipolar affective disorders) on serum olanzapine concentrations.

Conclusions:

The metabolism of olanzapine may be altered by several factors. Patients characterized with a combination of factors may benefit from therapeutic drug monitoring for the adjustment of olanzapine dose to minimize adverse reactions.
INTRAOCULAR PRESSURE OUTCOMES AFTER SURGERY FOR RHEGMATOGENOUS RETINAL DETACHMENT IN SCHWARTZ SYNDROME
Authors: Philip Reni , Balekudaru Shantha , Vijaya Lingam , George Ronnie
Published: February 2020

Purpose:

To study intraocular pressure (IOP) outcomes after surgery for rhegmatogenous retinal detachment in Schwartz syndrome.

Methods:

We reviewed records of 32 eyes of 32 patients with Schwartz syndrome (patients with rhegmatogenous retinal detachment, IOP above 21 mmHg, and open angles without angle recession, chronic steroid use or other secondary causes of increased IOP) who had undergone surgical treatment consisting of scleral buckling or vitrectomy. Intraocular pressure, number of medication, best-corrected visual acuity were compared at baseline and postsurgery visits and also studied association of various factors on long-term IOP.

Results:

The median duration of rhegmatogenous retinal detachment was 2 months, and the inter quartile range was 1 to 12 months. Follow-up was 15 months (inter quartile range: 7–33 months). Sixteen (50%) had prior ocular trauma. Baseline IOP was 35 ± 8 mmHg, and 12% (4/32) of patients were on IOP-lowering medication at presentation. At the final visit, mean IOP was 17 ± 6 mmHg and 59% patients (19/32) required additional IOP-lowering medication or surgery for IOP control.

Conclusion:

Surgical management of rhegmatogenous retinal detachment resulted in significant reduction in IOP. At the final visit, 41% did not require any IOP-lowering medication or surgical intervention for IOP control.
Clinical Features of Group A Streptococcus in Children With Pharyngitis: Carriers versus Acute Infection
Authors: Rick Anne-Marie , Zaheer Haniah A. , Martin Judith M.
Published: February 2020

Background:

Among children with pharyngitis who test positive for group A Streptococcus (GAS), 10%–25% are GAS carriers. Current laboratory methods cannot distinguish acute infection from colonization.

Methods:

We examined 2 separate longitudinal studies of children with symptomatic pharyngitis associated with a positive GAS throat culture (illness culture). In cohort 1, children presented with pharyngitis symptoms to a clinician, then had follow-up cultures at regular intervals. In cohort 2, throat cultures were performed at regular intervals and with pharyngitis symptoms. Illness cultures were categorized as acute infection or carrier based on follow-up culture results. In cohort 2, carriers were further categorized as a GAS carrier with a new emm-type or a GAS carrier with a previous emm-type based on typing data from prior culture results. For each cohort, symptoms were compared at the time of illness culture between carriers and those with acute infection.

Results:

Cohort 1 (N = 75 illness cultures): 87% of the children were classified as acutely infected versus 13% carriers. Carriers were more likely to have upper respiratory (URI) symptoms [odds ratio (OR): 5.5; 95% confidence interval (CI): 1.4–22.1], headache (OR: 6.0; 95% CI: 1.2–40.5) or vomiting (OR: 5.5; 95% CI: 1.2–24.5). Cohort 2 (N = 122 illness cultures): 79% were acutely infected and 21% were carriers. Children determined to be carriers with a previous detected emm-type were more likely to have URI symptoms compared with those with acquisition of a new emm-type.

Conclusions:

Children with symptomatic pharyngitis and GAS on throat culture identified as carriers were more likely to present with URI and atypical symptoms than children who were acutely infected.
Sleep disturbance underlies the co-occurrence of trauma and pediatric chronic pain: a longitudinal examination
Authors: Pavlova Maria , Kopala-Sibley Daniel C. , Nania Cara , Mychasiuk Richelle , Christensen Jennaya , McPeak Allison , Tomfohr-Madsen Lianne , Katz Joel , Palermo Tonya M. , Noel Melanie
Published: February 2020

Epidemiological and cross-sectional studies have shown that post-traumatic stress disorder symptoms (PTSS) are common and impairing in youth with chronic pain. Yet, the co-occurrence of PTSS and pediatric chronic pain has not been examined longitudinally, which has limited understanding of theoretically proposed mechanisms (eg, sleep disturbance) underlying the PTSS-pain relationship over time. This longitudinal study aimed to fill this gap. Participants included 138 youth (Mage = 14.29, 75% girls) referred to a tertiary-level outpatient chronic pain program and one of their parents. At baseline, youth reported their pain intensity and interference, PTSS, and subjective sleep disturbances (ie, sleep quality and insomnia). Youth and parents completed semistructured diagnostic interviews to determine the child's post-traumatic stress disorder diagnostic status, and youth completed an objective assessment of sleep patterns for 7 days using actigraphy. At 3-month follow-up, youth once again completed the diagnostic interview and reported their pain intensity, pain interference, and PTSS. Partially latent cross-lagged structural equation panel models revealed that, controlling for pain intensity, pain interference and PTSS co-occurred at baseline, but not at follow-up (while controlling for baseline levels). Higher levels of baseline PTSS were predictive of increases in pain interference at follow-up. Furthermore, subjective sleep disturbances mediated the relationship between baseline PTSS and follow-up pain interference. These findings lend support to conceptual models of PTSS–pain co-occurrence and highlight a critical need to assess and address trauma and sleep disturbances in youth with chronic pain.
Morphine produces potent antinociception, sedation, and hypothermia in humanized mice expressing human mu-opioid receptor splice variants
Authors: Huang Yi-Han , Wu Yu-Wei , Chuang Jian-Ying , Chang Yung-Chiao , Chang Hsiao-Fu , Tao Pao-Luh , Loh Horace H. , Yeh Shiu-Hwa
Published: February 2020

Morphine is a strong painkiller acting through mu-opioid receptor (MOR). Full-length 7-transmembrane (TM) variants of MOR share similar amino acid sequences of TM domains in rodents and humans; however, interspecies differences in N- and C-terminal amino acid sequences of MOR splice variants dramatically affect the downstream signaling. Thus, it is essential to develop a mouse model that expresses human MOR splice variants for opioid pharmacological studies. We generated 2 lines of fully humanized MOR mice (hMOR+; mMOR−/− mice), line #1 and #2. The novel murine model having human OPRM1 genes and human-specific variants was examined by reverse-transcription polymerase chain reaction and the MinION nanopore sequencing. The differences in the regional distribution of MOR between wild-type and humanized MOR mice brains were detected by RNAscope and radioligand binding assay. hMOR+; mMOR−/− mice were characterized in vivo using a tail-flick, charcoal meal, open field, tail suspension, naloxone precipitation tests, and rectal temperature measurement. The data indicated that wild-type and humanized MOR mice exhibited different pharmacology of morphine, including antinociception, tolerance, sedation, and withdrawal syndromes, suggesting the presence of species difference between mouse and human MORs. Therefore, hMOR+; mMOR−/− mice could serve as a novel mouse model for pharmacogenetic studies of opioids.
Development of the Implantable Cardioverter Defibrillator Body Image Concerns Questionnaire
Authors: Frydensberg Vivi Skibdal , Strömberg Anna , Johansen Jens Brock , Pedersen Susanne S.
Published: February 2020

Background

The implantable cardioverter defibrillator (ICD) is the first-line treatment for the prevention of sudden cardiac death. Although most ICD recipients adapt well to living with the device, some struggle with ICD-related body image concerns (BICs). Because of lack of standardized questionnaires to assess BICs, we do not know the prevalence.

Objective

The aim of this study was to develop a questionnaire that assesses self-reported ICD-related BICs.

Methods

Using a sequential, qualitative multimethod approach, we developed the ICD-BIC questionnaire (ICD-BICQ) based on (1) themes from a scoping review on BICs in ICD recipients, (2) cognitive interviews with ICD recipients to evaluate the validity of items and to ascertain whether items were missing, and (3) input from healthcare professionals. A conceptual framework was created containing 4 general dimensions: (1) assessment, (2) behavior, (3) body perception, and (4) emotions.

Results

Implantable cardioverter defibrillator recipients (n = 8, 2 women and 6 men; age, 40–78 years), 2 specialists in questionnaire development, and healthcare professionals specialized in ICD treatment evaluated the questionnaire. After no new items or new dimensions emerged from the cognitive interviews, the final version 7 of the ICD-BICQ consisted of 39 items tapping into (1) assessment (n = 2), (2) behavior (n = 13), (3) body perception (n = 16), and emotions (n = 8). Items were assessed on a 5-point Likert-type scale.

Conclusion

Using patient and healthcare professionals' involvement, we developed the 39-item ICD-BICQ to measure the prevalence of BICs in ICD recipients. The factor structure, construct validity, psychometric properties, and a clinically relevant cutoff for the ICD-BICQ will be evaluated in a quantitative study of ICD recipients.
Partnering with parents to remove barriers and improve influenza immunization rates for young children
Authors: Bauer Katherine E. , Agruss Janyce Cagan , Mayefsky Jay H.
Published: February 2020

Background:

Despite the ongoing public health initiatives to increase pediatric influenza immunization rates to 80%, only a few US health centers have been able to meet this goal. The suboptimal immunity to influenza poses individual and societal risks for vaccine-preventable cases of influenza and its complications.

Local problem:

At a diverse, urban, family health center, its influenza immunization rate of 44% represented the lowest uptake rate compared with all other early childhood vaccines, increasing the risk of morbidity and mortality in young children, including hospitalization and death.

Methods:

To identify key barriers to influenza immunization, the investigators interviewed parents of children aged 6 through 24 months at this urban family health center via randomized sampling using an open-ended telephone survey.

Interventions:

Based on the concerns parents expressed through the survey, a program was designed and implemented that included reminder calls, parent education, proactive appointment scheduling, and social media reminders.

Results:

After implementing a parent-driven quality-improvement program for 6 months during influenza season, the health center's pediatric influenza immunization rates rose to 57% compared with 44% during the year before.

Conclusions:

Childhood immunization is a critical priority to protect the health and wellness of children. Increasing parent engagement in discussions about increasing immunization rates not only promotes awareness surrounding vaccines but also allows primary care providers to learn from parents to create a patient-centered immunization program. Programs that specifically target immunization efforts toward parental concerns have the potential for increased vaccine acceptance and improved health outcomes.