bluuebunny/crossref_metadata_2025 huggingface dataset:
Disentangling the Relationship Between Self-Esteem and Problematic Alcohol Use Among College Students: Evidence From a Cluster Analytic Approach
Authors: Gierski Fabien , De Wever Elodie , Benzerouk Farid , Lannoy Séverine , Kaladjian Arthur , Naassila Mickaël , Quaglino Véronique
Published: October 2019

Aims

Investigation of the relationship between self-esteem and alcohol use among college students has yielded discrepant results. We hypothesized that these discrepancies could originate from a potential heterogeneity of self-esteem patterns among young adult with an alcohol use disorder (AUD).

Methods

A community sample of 343 college students was recruited and categorized with or without AUD using the Alcohol Use Disorders Identification Test cut-offs. College students were compared on the dimensions of the Coopersmith Self-Esteem Inventory (CSEI) as well as mood, impulsiveness, alcohol- and other substance-related measures, including drinking motives.

Results

A cluster analysis conducted among college students with AUD highlighted two subgroups characterized by contrasting patterns on the CSEI: one group with a high level of self-esteem and low levels of anxiety and depression symptoms and one group with a low level of self-esteem and high levels of impulsiveness, mood symptoms and drinking to cope motives.

Conclusion

Findings caution against assuming that AUD is associated with low self-esteem, as reported in previous studies. These results rather emphasize a heterogeneity of self-esteem in college students, showing that high self-esteem was also related to AUD. Implications of these results are major for prevention purposes and clinical practice.
28 USC § 1782—looking for consensus
Authors: Stute David J
Published: October 2019

Since the 1948 enactment of 28 USC § 1782 in the United States, no consensus has emerged as to the availability of federal court discovery to parties in private foreign or international arbitral proceedings. This year, within months of one another, six federal courts have issued rulings that are widely inconsistent on the availability of section 1782 discovery. The courts have ruled that a proceeding before a private international arbitral tribunal is eligible for section 1782 discovery; that, categorically, no such discovery is available; that the definition of private arbitral tribunal applies to CIETAC; and that discovery is available by virtue of a party’s parallel pursuit of discovery through foreign civil proceedings. As these cases demonstrate, recent US court decisions have brought no predictability, let alone certainty, to the subject. Congress, on the other hand, could and should amend the statute so as to include private tribunals in the scope of section 1782. This article discusses the case law’s state of disarray; proposes a legislative solution; considers the proposed amendment’s merits; and advocates for Congress to act.
Effects of experimental lead exposure on physiological indices of nestling great tits Parus major: haematocrit and heterophile-to-lymphocyte ratio
Authors: Markowski Marcin , Kaliński Adam , Bańbura Mirosława , Glądalski Michał , Wawrzyniak Jarosław , Skwarska Joanna , Bańbura Jerzy
Published: October 2019

This study applies a field experimental approach to an issue of single lead exposures and their effects on specific haematologial indices in nestling songbirds. We used nestling great tits Parus major as a model and showed that higher lead exposure was associated with significant haematocrit decline. In contrast, the assessment of the H/L ratio revealed no significant effect of a single lead exposure.
The Mitochondrial Genome of Eleusine indica and Characterization of Gene Content Within Poaceae
Authors: Hall Nathan D , Zhang Hui , Mower Jeffrey P , McElroy J Scott , Goertzen Leslie R
Published: October 2019

Plant mitochondrial (mt) genome assembly provides baseline data on size, structure and gene content, but resolving the sequence of these large and complex organelle genomes remains challenging due to fragmentation, frequent recombination, and transfers of DNA from neighboring plastids. The mitochondrial genome for Eleusine indica (Poaceae: goosegrass) is comprehensibly analyzed here, providing key reference data for an economically significant invasive species that is also the maternal parent of the allotetraploid crop Finger millet (Eleusine coracana). The assembled E. indica genome contains 33 protein coding genes, 6 rRNA subunits, 24 tRNA, 8 large repetitive regions 15 kb of transposable elements across a total of 520,691 bp. Evidence of RNA editing and loss of rpl2, rpl5, rps14, rps11, sdh4 and sdh3 genes is evaluated in the context of an updated survey of mt genomic gene content across the grasses through an analysis of available publicly available data. Hypothesized patterns of Poaceae mt gene loss are examined in a phylogenetic context to clarify timing, showing that rpl2 was transferred to the nucleus from the mitochondrion prior to the origin of the PACMAD clade.
Injection-induced seismicity: strategies for reducing risk using high stress path reservoirs and temperature-induced stress preconditioning
Authors: Fryer B , Siddiqi G , Laloui L
Published: October 2019

It is suggested that fluid injection in normal faulting stress regimes can stabilize a reservoir if the stress path is high enough. This stabilization is not seen when the reservoir is significantly cooled as a result of injection. Further, a new strategy is suggested for stimulating reservoirs in shear with a reduced chance of inducing a large magnitude seismic event. The version of this methodology presented here is applicable for reverse faulting stress regimes and involves an initial stress preconditioning stage where the reservoir is cooled and the pressure increase is limited. This process reduces the horizontal total stress and thereby also the differential stress. Next, the reservoir is stimulated with a rapid increase in pore pressure, resulting in shear failure at a lower differential stress than was initially present in the reservoir. Due to the connection seen between the Gutenberg–Richter b-value and differential stress, it is suggested that reservoirs stimulated in this fashion will exhibit higher b-values and thereby also have a reduced chance of hosting a large magnitude event. It is suggested that adaptations of this methodology are applicable to both normal and strike-slip faulting stress regimes.
Health service utilization and direct healthcare costs associated with obesity in older adult population in Ghana
Authors: Lartey Stella T , de Graaff Barbara , Magnussen Costan G , Boateng Godfred O , Aikins Moses , Minicuci Nadia , Kowal Paul , Si Lei , Palmer Andrew J
Published: October 2019

Obesity is a major risk factor for many chronic diseases and disabilities, with severe implications on morbidity and mortality among older adults. With an increasing prevalence of obesity among older adults in Ghana, it has become necessary to develop cost-effective strategies for its management and prevention. However, developing such strategies is challenging as body mass index (BMI)-specific utilization and costs required for cost-effectiveness analysis are not available in this population. Therefore, this study examines the associations between health services utilization as well as direct healthcare costs and overweight (BMI ≥25.00 and <30.00 kg/m2) and obesity (BMI ≥30.00 kg/m2) among older adults in Ghana. Data were used from a nationally representative, multistage sample of 3350 people aged 50+ years from the World Health Organization’s Study on global AGEing and adult health (WHO-SAGE; 2014/15). Health service utilization was measured by the number of health facility visits over a 12-month period. Direct costs (2017 US dollars) included out-of-pocket payments and the National Health Insurance Scheme (NHIS) claims. Associations between utilization and BMI were examined using multivariable zero-inflated negative binomial regressions; and between costs and BMI using multivariable two-part regressions. Twenty-three percent were overweight and 13% were obese. Compared with normal-weight participants, overweight and obesity were associated with 75% and 159% more inpatient admissions, respectively. Obesity was also associated with 53% additional outpatient visits. One in five of the overweight and obese population had at least one chronic disease, and having chronic disease was associated with increased outpatient utilization. The average per person total costs for overweight was $78 and obesity was $132 compared with $35 for normal weight. The NHIS bore approximately 60% of the average total costs per person expended in 2014/15. Overweight and obese groups had significantly higher total direct healthcare costs burden of $121 million compared with $64 million for normal weight in the entire older adult Ghanaian population. Compared with normal weight, the total costs per person associated with overweight increased by 73% and more than doubled for obesity. Even though the total prevalence of overweight and obesity was about half of that of normal weight, the sum of their cost burden was almost doubled. Implementing weight reduction measures could reduce health service utilization and costs in this population.
Antibiotic appropriateness and guideline adherence in hospitalized children: results of a nationwide study
Authors: McMullan Brendan J , Hall Lisa , James Rodney , Mostaghim Mona , Jones Cheryl A , Konecny Pamela , Blyth Christopher C , Thursky Karin A
Published: October 2019

Background

Information on the nature and appropriateness of antibiotic prescribing for children in hospitals is important, but scarce.

Objectives

To analyse antimicrobial prescribing and appropriateness, and guideline adherence, in hospitalized children across Australia.

Patients and methods

We analysed data from the National Antimicrobial Prescribing Survey (NAPS) from 2014 to 2017. Surveys were performed in hospital facilities of all types (public and private; major city, regional and remote). Participants were admitted children <18 years old. Risk factors associated with inappropriate prescribing were explored using logistic regression models.

Results

Among 6219 prescriptions for 3715 children in 253 facilities, 19.6% of prescriptions were deemed inappropriate. Risk factors for inappropriate prescribing included non-tertiary paediatric hospital admission [OR 1.37 (95% CI 1.20–1.55)] and non-major city hospital location [OR 1.52 (95% CI 1.30–1.77)]. Prescriptions for neonates, immunocompromised children and those admitted to an ICU were less frequently inappropriate. If a restricted antimicrobial was prescribed and not approved, the prescription was more likely to be inappropriate [OR 12.9 (95% CI 8.4–19.8)]. Surgical prophylaxis was inappropriate in 59% of prescriptions.

Conclusions

Inappropriate antimicrobial prescribing in children was linked to specific risk factors identified here, presenting opportunities for targeted interventions to improve prescribing. This information, using a NAPS dataset, allows for analysis of antimicrobial prescribing among different groups of hospitalized children. Further exploration of barriers to appropriate prescribing and facilitators of best practice in this population is recommended.
Evaluation of target attainment of oral posaconazole suspension in immunocompromised children
Authors: Lai Tony , Alffenaar Jan-Willem , Kesson Alison , Bandodkar Sushil , Roberts Jason A
Published: October 2019

Background

Posaconazole is a broad-spectrum antifungal that is not licensed for use in children <13 years of age. Despite this and by necessity, it is used extensively in paediatric hospitals for prophylaxis of invasive fungal disease.

Objectives

To determine whether initial prophylactic dosing recommendations attain a posaconazole plasma concentration of ≥700 ng/mL in immunocompromised children <13 years of age.

Patients and methods

We performed a retrospective study of immunocompromised children <13 years of age receiving posaconazole suspension prophylaxis at a starting dose of 5 mg/kg every 8 h for ≥7 days and who had a posaconazole concentration measured after ≥7 days. Posaconazole plasma concentrations and rate of breakthrough infection were recorded.

Results

A total of 70 patients were included with a median age of 5 years (range 3 months to 12 years). The mean posaconazole plasma concentration was 783.4 ng/mL (IQR 428.3–980 ng/mL) and the percentage of patients with a posaconazole plasma concentration ≥700ng/mL was 47.9%. Patients who were on a proton pump inhibitor, a histamine H2 antagonist or metoclopramide, had mucositis or were enterally fed had a lower posaconazole plasma concentration compared with patients without these co-administered drugs/mucositis/enteral feeding (542.3 versus 1069.8 ng/mL; P<0.001). The breakthrough invasive fungal infection rate was 4.3% (3/70).

Conclusions

The studied 5 mg/kg posaconazole suspension every 8 h resulted in target concentrations in only 47.9% of patients and further studies looking at newer posaconazole formulations are needed.
Phase III Randomized Trial of Bisphosphonates as Adjuvant Therapy in Breast Cancer: S0307
Authors: Gralow Julie R , Barlow William E , Paterson Alexander H G , M'iao Jieling L , Lew Danika L , Stopeck Alison T , Hayes Daniel F , Hershman Dawn L , Schubert Mark M , Clemons Mark , Van Poznak Catherine H , Dees Elizabeth C , Ingle James N , Falkson Carla I , Elias Anthony D , Messino Michael J , Margolis Jeffrey H , Dakhil Shaker R , Chew Helen K , Dammann Kim Z , Abrams Jeffrey S , Livingston Robert B , Hortobagyi Gabriel N
Published: October 2019

Background

Adjuvant bisphosphonates, when given in a low-estrogen environment, can decrease breast cancer recurrence and death. Treatment guidelines include recommendations for adjuvant bisphosphonates in postmenopausal patients. SWOG/Alliance/Canadian Cancer Trials Group/ECOG-ACRIN/NRG Oncology study S0307 compared the efficacy of three bisphosphonates in early-stage breast cancer.

Methods

Patients with stage I–III breast cancer were randomly assigned to 3 years of intravenous zoledronic acid, oral clodronate, or oral ibandronate. The primary endpoint was disease-free survival (DFS) with overall survival as a secondary outcome. All statistical tests were two-sided.

Results

A total of 6097 patients enrolled. Median age was 52.7 years. Prior to being randomly assigned, 73.2% patients indicated preference for oral vs intravenous formulation. DFS did not differ across arms in a log-rank test (P = .49); 5-year DFS was 88.3% (zoledronic acid: 95% confidence interval [CI] = 86.9% to 89.6%), 87.6% (clodronate: 95% CI = 86.1% to 88.9%), and 87.4% (ibandronate: 95% CI = 85.6% to 88.9%). Additionally, 5-year overall survival did not differ between arms (log rank P = .50) and was 92.6% (zoledronic acid: 95% CI = 91.4% to 93.6%), 92.4% (clodronate: 95% CI = 91.2% to 93.5%), and 92.9% (ibandronate: 95% CI = 91.5% to 94.1%). Bone as first site of recurrence did not differ between arms (P = .93). Analyses based on age and tumor subtypes showed no treatment differences. Grade 3/4 toxicity was 8.8% (zoledronic acid), 8.3% (clodronate), and 10.5% (ibandronate). Osteonecrosis of the jaw was highest for zoledronic acid (1.26%) compared with clodronate (0.36%) and ibandronate (0.77%).

Conclusions

We found no evidence of differences in efficacy by type of bisphosphonate, either in overall analysis or subgroups. Despite an increased rate of osteonecrosis of the jaw with zoledronic acid, overall toxicity grade differed little across arms. Given that patients expressed preference for oral formulation, efforts to make oral agents available in the United States should be considered.
Targeted axillary dissection in breast cancer by marking lymph node metastasis with a magnetic seed before starting neoadjuvant treatment
Authors: García-Moreno Joaquín Luis , Benjumeda-Gonzalez Ana María , Amerigo-Góngora Marta , Landra-Dulanto Piero José , Gonzalez-Corena Yisela , Gomez-Menchero Julio
Published: October 2019

We report the first documented clinical case of the use of magnetic seeds to mark axillary lymph node metastasis in breast cancer before neoadjuvant chemotherapy. After chemotherapy, the patient showed a complete radiological response. One single sentinel lymph node was detected using a radiotracer, while the marked node was intraoperative magnetometer-guided identified. The analysis of the nodes showed negative sentinel lymph node and positive marked node, and the subsequent targeted axillary dissection was performed. Marking axillary positive lymph nodes with a magnetic seed is a simple and effective procedure for the intraoperative localisation of the node after neoadjuvant treatment.
Quantum ion thermodynamics in liquid interiors of white dwarfs
Authors: Baiko D A , Yakovlev D G
Published: October 2019

We present an accurate analytic approximation for the energy of a quantum one-component Coulomb liquid of ions in a uniform electron background that has been recently calculated from first principles. The approximation enables us to develop in an analytic form a complete thermodynamic description of quantum ions in a practically important range of mass densities at temperatures above crystallization. We show that ionic quantum effects in liquid cores of white dwarfs (WDs) affect heat capacity, cooling, thermal compressibility, pulsation frequencies, and radii of sufficiently cold WDs, especially with relatively massive helium and carbon cores.
Chromospheric emission of solar-type stars with asteroseismic ages
Authors: Booth R S , Poppenhaeger K , Watson C A , Silva Aguirre V , Stello D , Bruntt H
Published: October 2019

Stellar magnetic activity decays over the main-sequence life of cool stars due to the stellar spin-down driven by magnetic braking. The evolution of chromospheric emission is well studied for younger stars, but difficulties in determining the ages of older cool stars on the main sequence have complicated such studies for older stars in the past. Here, we report on chromospheric Ca ii H and K line measurements for 26 main-sequence cool stars with asteroseismic ages older than a gigayear and spectral types F and G. We find that for the G stars and the cooler F-type stars that still have convective envelopes the magnetic activity continues to decrease at stellar ages above 1 Gyr. Our magnetic activity measurements do not show evidence for a stalling of the magnetic braking mechanism, which has been reported for stellar rotation versus age for G- and F-type stars. We also find that the measured $R^{\prime }_{\mathrm{ HK}}$ indicator value for the cool F stars in our sample is lower than predicted by common age–activity relations that are mainly calibrated on data from young stellar clusters. We conclude that, within individual spectral type bins, chromospheric magnetic activity correlates well with stellar age even for old stars.
Diverse properties of Ly α emission in low-redshift compact star-forming galaxies with extremely high [O iii]/[O ii] ratios
Authors: Izotov Y I , Schaerer D , Worseck G , Verhamme A , Guseva N G , Thuan T X , Orlitová I , Fricke K J
Published: October 2019

We present observations with the Cosmic Origins Spectrograph onboard the Hubble Space Telescope of eight compact star-forming galaxies at redshifts z = 0.02811–0.06540, with low oxygen abundances 12 + log(O/H) = 7.43–7.82 and extremely high emission-line flux ratios O32 = [O iii] λ5007/[O ii] λ3727 ∼ 22–39, aiming to study the properties of Ly α emission in such conditions. We find a diversity in Ly α properties. In five galaxies Ly α emission line is strong, with equivalent width (EW) in the range 45–190 Å. In the remaining galaxies, weak Ly α emission with EW(Ly α) ∼ 2–7 Å is superposed on a broad Ly α absorption line, indicating a high neutral hydrogen column density N(H i) ∼ (1 – 3)× 1021 cm−2. We examine the relation between the Ly α escape fraction fesc(Ly α) and the Lyman continuum escape fraction fesc(LyC), using direct measures of the latter in eleven low-redshift LyC leakers, to verify whether fesc(Ly α) can be an indirect measure of escaping LyC radiation. The usefulness of O32, of the Ly α equivalent width EW(Ly α), and of the Ly α peak separation Vsep as indirect indicators of Ly α leakage is also discussed. It is shown that there is no correlation between O32 and fesc(Ly α). We find an increase of fesc(Ly α) with increasing EW(Ly α) for EW(Ly α) <100 Å, but for higher EW(Ly$\alpha)\gtrsim$150 Å the fesc(Ly α) is nearly constant attaining the value of ∼0.25. We find an anticorrelation between fesc(Ly α) and Vsep, though not as tight as the one found earlier between fesc(LyC) and Vsep. This finding makes Vsep a promising indirect indicator of both the Ly α and ionizing radiation leakage.
Dissecting the Transcriptomic Basis of Phenotypic Evolution in an Aquatic Keystone Grazer
Authors: Frisch Dagmar , Becker Dörthe , Wojewodzic Marcin W
Published: October 2019

Knowledge of the molecular basis of phenotypic responses to environmental cues is key to understanding the process of adaptation. Insights to adaptation at an evolutionary time scale can be gained by observing organismal responses before and after a shift in environmental conditions, but such observations can rarely be made. Using the ecological and genomic model Daphnia, we linked transcriptomic responses and phosphorus (P)-related phenotypic traits under high and low P availability. We mapped weighted gene coexpression networks to traits previously assessed in resurrected ancient (600 years old) and modern Daphnia pulicaria from a lake with a historic shift in P-enrichment. Subsequently, we assessed evolutionary conservation or divergence in transcriptional networks of the same isolates. We discovered highly preserved gene networks shared between ancient genotypes and their modern descendants, but also detected clear evidence of transcriptional divergence between these evolutionarily separated genotypes. Our study highlights that phenotypic evolution is a result of molecular fine-tuning on different layers ranging from basic cellular responses to higher order phenotypes. In a broader context, these findings advance our understanding how populations are able to persist throughout major environmental shifts.
Loss of the ribosomal RNA methyltransferase NSUN5 impairs global protein synthesis and normal growth
Authors: Heissenberger Clemens , Liendl Lisa , Nagelreiter Fabian , Gonskikh Yulia , Yang Guohuan , Stelzer Elena M , Krammer Teresa L , Micutkova Lucia , Vogt Stefan , Kreil David P , Sekot Gerhard , Siena Emilio , Poser Ina , Harreither Eva , Linder Angela , Ehret Viktoria , Helbich Thomas H , Grillari-Voglauer Regina , Jansen-Dürr Pidder , Koš Martin , Polacek Norbert , Grillari Johannes , Schosserer Markus
Published: October 2019

Modifications of ribosomal RNA expand the nucleotide repertoire and thereby contribute to ribosome heterogeneity and translational regulation of gene expression. One particular m5C modification of 25S ribosomal RNA, which is introduced by Rcm1p, was previously shown to modulate stress responses and lifespan in yeast and other small organisms. Here, we report that NSUN5 is the functional orthologue of Rcm1p, introducing m5C3782 into human and m5C3438 into mouse 28S ribosomal RNA. Haploinsufficiency of the NSUN5 gene in fibroblasts from William Beuren syndrome patients causes partial loss of this modification. The N-terminal domain of NSUN5 is required for targeting to nucleoli, while two evolutionary highly conserved cysteines mediate catalysis. Phenotypic consequences of NSUN5 deficiency in mammalian cells include decreased proliferation and size, which can be attributed to a reduction in total protein synthesis by altered ribosomes. Strikingly, Nsun5 knockout in mice causes decreased body weight and lean mass without alterations in food intake, as well as a trend towards reduced protein synthesis in several tissues. Together, our findings emphasize the importance of single RNA modifications for ribosome function and normal cellular and organismal physiology.
Betacellulin drives therapy resistance in glioblastoma
Authors: Fan Qiwen , An Zhenyi , Wong Robyn A , Luo Xujun , Lu Edbert D , Baldwin Albert , Mayekar Manasi K , Haderk Franziska , Shokat Kevan M , Bivona Trever G , Weiss William A
Published: October 2019

Background

The transcription factor signal transducer and activator of transcription 3 (STAT3) drives progression in glioblastoma (GBM), suggesting STAT3 as a therapeutic target. Surprisingly however, GBM cells generally show primary resistance to STAT3 blockade.

Methods

Human glioblastoma cell lines LN229, U87, SF767, and U373, and patient-derived xenografts (PDXs) GBM8 and GBM43 were used to evaluate epidermal growth factor receptor (EGFR) activation during STAT3 inhibition. Protein and gene expression experiments, protein stability assays, cytokine arrays, phospho-tyrosine arrays and EGFR-ligand protein arrays were performed on STAT3 inhibitor–treated cells. To evaluate antitumor activity, we administered a betacellulin (BTC)-neutralizing antibody alone and in combination with STAT3 inhibition. BTC is an EGFR ligand. We therefore treated mice with orthotopic xenografts using the third-generation EGFR inhibitor osimertinib, with or without STAT3 knockdown.

Results

We demonstrate that both small-molecule inhibitors and knockdown of STAT3 led to expression and secretion of the EGFR ligand BTC, resulting in activation of EGFR and subsequent downstream phosphorylation of nuclear factor-kappaB (NF-κB). Neutralizing antibody against BTC abrogated activation of both EGFR and NF-κB in response to inhibition of STAT3; with combinatorial blockade of STAT3 and BTC inducing apoptosis in GBM cells. Blocking EGFR and STAT3 together inhibited tumor growth, improving survival in mice bearing orthotopic GBM PDXs in vivo.

Conclusion

These data reveal a feedback loop among STAT3, EGFR, and NF-κB that mediates primary resistance to STAT3 blockade and suggest strategies for therapeutic intervention.
Variation and implications of treatment decisions in early rheumatoid arthritis: results from a nationwide cohort study
Authors: Yates Mark , MacGregor Alexander J , Ledingham Jo , Norton Sam , Bechman Katie , Dennison Elaine M , Galloway James B
Published: October 2019

Objectives

Trial data have provided an evidence base to guide early treatment in RA. Few studies have investigated rheumatologists’ adherence to guidelines, and subsequent impact on outcomes. The objectives of this study are to characterize baseline prescribing for patients with RA across the National Health Service, identifying treatment decisions that associate with patient outcomes.

Methods

A nationwide audit of RA collected information on treatment choices, DAS and sociodemographic factors at baseline. Treatment response was assessed at 3 months. Multilevel regression models were used to characterize departmental variations in prescribing. Heat maps were used to visualize geographical variation. Mixed effects regression models were constructed to assess the relationship between treatment decisions and disease outcomes, adjusting for patient and department level covariates.

Results

A total of 7154 patients with a diagnosis of RA were recruited from 136 departments. There was broad variation in prescribing choices, even between departments close to one another, with evidence of substantial deviation from guidelines. Over 75% of patients received glucocorticoids, fewer than half received combination conventional DMARDs. Early glucocorticoid therapy associated with achieving a good treatment response [odds ratio 1.93 (95% CI 1.31, 2.84), P-value = 0.001]. The association was maintained following propensity modelling and imputation.

Conclusion

Guideline adherence varies between departments and cannot be explained by case-mix alone. Departments that prescribe early adjunctive steroid achieve better short-term outcomes. Further research should work to ensure that the early arthritis evidence base translates into better outcomes for patients.
Assessment for varicella zoster virus in patients newly suspected of having giant cell arteritis
Authors: Sammel Anthony M , Smith Susan , Nguyen Katherine , Laurent Rodger , Brewer Janice , Hall Nathan , Little Christopher B
Published: October 2019

Objectives

There is uncertainty if varicella zoster virus (VZV) triggers GCA. This is based on discordant reports of VZV detection in GCA temporal artery biopsies. We conducted a multimodal evaluation for VZV in the inception Giant Cell Arteritis and PET Scan (GAPS) cohort.

Methods

Consecutive patients who underwent temporal artery biopsy for suspected GCA were clinically reviewed for active and past VZV infection and followed for 6 months. Serum was tested for VZV IgM and IgG. Temporal artery biopsy (TAB) sections were stained for VZV antigen using the VZV Mouse Cocktail Antibody (Cell Marque, Rocklin, CA, USA). A selection of GCA and control tissues were stained with the VZV gE antibody (Santa Cruz Biotechnology, Dallas, TX, USA), which was used in previous studies.

Results

A total of 58 patients met inclusion criteria, 12 (21%) had biopsy-positive GCA and 20 had clinically positive GCA. None had herpes zoster at enrolment and only one patient developed a VZV clinical syndrome (zoster ophthalmicus) on follow-up. There was no difference in VZV exposure between GCA and non-GCA patients. None of the 53 patients who had VZV serology collected had positive VZV IgM antibodies. VZV antigen was not convincingly demonstrated in any of the TAB specimens; 57 TABs stained negative and 1 stained equivocally positive. The Santa Cruz Biotechnology VZV antibody exhibited positive staining in a range of negative control tissues, questioning its specificity for VZV antigen.

Conclusion

The absence of active infection markers argues against VZV reactivation being the trigger for GCA. Non-specific immunohistochemistry staining may account for positive findings in previous studies.
Networks and new mutualism: how embeddedness influences commitment and trust in small mutuals
Authors: Vriens Eva , Buskens Vincent , de Moor Tine
Published: October 2019

Mutualism is reviving again in several countries, replying to state and market failure with an alternative, social insurance setup. We study participation in such new mutuals with a focus on embeddedness. We distinguish group-level embeddedness (network structure) and individual embeddedness (the type and quantity of ties to other group members) and study how these relate to members’ commitment to mutuals and their trust in the commitment of others. We show that group-level embeddedness primarily affects trust, while individual embeddedness more strongly associates with commitment. We reveal these dynamics for mutuals of different ages using a unique multilevel dataset on the motivations, beliefs and social relations of more than 5000 members of 230 small Dutch mutuals. Our results highlight the importance of thinking critically about the levels at which social embeddedness plays a role, as the dynamics are more subtle and not all means of embeddedness are equally fruitful.
Chronic venous insufficiency
Authors: Berti-Hearn Linda , Elliott Brenda
Published: October 2019

Chronic venous insufficiency (CVI) is a potentially debilitating disorder associated with serious complications such as lower extremity venous ulcers. This article reviews the incidence and pathophysiology of CVI, nursing assessment, diagnosis and interventions, and patient education needed to manage the disease and prevent complications.
A Multicenter, Randomized, Double-blind, Parallel, Placebo-controlled Clinical Study to Evaluate the Efficacy and Safety of a Nicotine Mint Lozenge (2 and 4 mg) in Smoking Cessation
Authors: Xiao Dan , Kotler Mitchell , Kang Jian , Wang Chen
Published: October 2019

Objective:

To evaluate the efficacy in smoking cessation and safety of 2 and 4 mg nicotine mint lozenges in Chinese adult smokers.

Methods:

This was a multicenter, randomized, stratified, double-blind, placebo-controlled, parallel-group study. The low-dependence stratum included 483 smokers (241 randomized to active 2 mg nicotine lozenge and 242 to placebo lozenge). The high-dependence stratum included 240 smokers (120 randomized to active 4 mg nicotine lozenge and 120 to placebo lozenge). The primary endpoint was successful smoking cessation at 6 weeks postquit, defined as continuous abstinence from smoking for the 28-day period up to and including the 6-week visit (verified by CO measurement). Cochran–Mantel–Haenszel tests were performed to compare quit rates between active nicotine and placebo separately for the high-dependence and low-dependence strata.

Results:

The primary analysis showed that in the low-dependence (2 mg) stratum, 59 subjects (24.5%) of 241 in the active nicotine group and 52 subjects (21.5%) of 242 in the placebo group were successful quitters (P = .3851). In the high-dependence (4 mg) stratum, 37 subjects (30.8%) of 120 in the active nicotine group and 24 subjects (20.2%) of 119 in the placebo group were successful quitters (P = .0565).

Conclusions:

The 4 mg nicotine lozenge provided a directionally significant improvement in smoking cessation rates compared with placebo in Chinese adult smokers with high nicotine dependence for the primary endpoint. The 2 mg nicotine lozenge provided higher, but nonsignificant, smoking cessation rates than placebo. Both nicotine lozenges were generally well tolerated in Chinese adult smokers.
Sevoflurane Promotes Bactericidal Properties of Macrophages through Enhanced Inducible Nitric Oxide Synthase Expression in Male Mice
Authors: Gerber Thomas J. , Fehr Valérie C. O. , Oliveira Suellen D. S. , Hu Guochang , Dull Randal , Bonini Marcelo G. , Beck-Schimmer Beatrice , Minshall Richard D.
Published: October 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Sevoflurane with its antiinflammatory properties has shown to decrease mortality in animal models of sepsis. However, the underlying mechanism of its beneficial effect in this inflammatory scenario remains poorly understood. Macrophages play an important role in the early stage of sepsis as they are tasked with eliminating invading microbes and also attracting other immune cells by the release of proinflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α. Thus, the authors hypothesized that sevoflurane mitigates the proinflammatory response of macrophages, while maintaining their bactericidal properties.

Methods

Murine bone marrow–derived macrophages were stimulated in vitro with lipopolysaccharide in the presence and absence of 2% sevoflurane. Expression of cytokines and inducible NO synthase as well as uptake of fluorescently labeled Escherichia coli (E. coli) were measured. The in vivo endotoxemia model consisted of an intraperitoneal lipopolysaccharide injection after anesthesia with either ketamine and xylazine or 4% sevoflurane. Male mice (n = 6 per group) were observed for a total of 20 h. During the last 30 min fluorescently labeled E. coli were intraperitoneally injected. Peritoneal cells were extracted by peritoneal lavage and inducible NO synthase expression as well as E. coli uptake by peritoneal macrophages was determined using flow cytometry.

Results

In vitro, sevoflurane enhanced lipopolysaccharide-induced inducible NO synthase expression after 8 h by 466% and increased macrophage uptake of fluorescently labeled E. coli by 70% compared with vehicle-treated controls. Inhibiting inducible NO synthase expression pharmacologically abolished this increase in bacteria uptake. In vivo, inducible NO synthase expression was increased by 669% and phagocytosis of E. coli by 49% compared with the control group.

Conclusions

Sevoflurane enhances phagocytosis of bacteria by lipopolysaccharide-challenged macrophages in vitro and in vivo via an inducible NO synthase–dependent mechanism. Thus, sevoflurane potentiates bactericidal and antiinflammatory host-defense mechanisms in endotoxemia.
Translation, Cross-cultural Adaptation, and Psychometric Properties of the Hausa Versions of the Numerical Pain Rating Scale and Global Rating of Change Scale in a Low-literate Population With Chronic Low Back Pain
Authors: Ibrahim Aminu A. , Akindele Mukadas O. , Bello Bashir , Kaka Bashir
Published: October 2019

Study Design.

Translation, cross-cultural adaptation, and psychometric testing.

Objective.

To translate, cross-culturally adapt, and validate the Numerical Pain Rating Scale (NPRS) and the Global Rating of Change Scale (GRCS) into Hausa language.

Summary of Background Data.

The NPRS and GRCS are commonly used patient-reported outcome measures in a variety of pain-related conditions including low back pain. To date, neither the NPRS nor GROC are available in Hausa language.

Methods.

The Hausa versions of the NPRS (NPRS-H) and GRCS (GRCS-H) were developed using recommended guidelines. The final versions were then administered to 120 patients with chronic low back pain to access their psychometric properties. Reliability assessment included calculations of intraclass correlation coefficient (ICC) and minimal detectable change among the stable group. Construct validity and concurrent validity were assessed using the Spearman rank correlation coefficient. Internal responsiveness was assessed using mean change scores, standardized effect size, and standard response mean. Receiver operating characteristic curves were plotted to determine the external responsiveness of the NPRS-H using the area under the curve, and minimal important change for small, medium, and large improvements. Outcome measures consisted of the Visual Analogue Scale for pain and Oswestry Disability Index.

Results.

The NPRS-H and GRCS-H were successfully developed. High test–retest reliability was demonstrated for both the NPRS-H (ICC = 0.95) and GRCS-H (ICC = 0.94) with minimal detectable change points of 1.0 and 1.2 respectively. The scales showed moderate to strong correlation with the Visual Analogue Scale for pain and Oswestry Disability Index. The mean change of the NPRS-H scores correlated moderately with the GRCS-H. Both scales demonstrated good internal responsiveness. External responsiveness of the NPRS-H was demonstrated at three levels with area under the curve  = 0.875 to 0.972, and minimal important change  = 2.5 to 3.5.

Conclusions.

The NPRS and GRCS were successfully adapted into Hausa language with acceptable reliability, validity, and responsiveness. These measures are appropriate for clinical and research use among Hausa-speaking patients.

Level of Evidence: 2
A dual cancer-specific recombinant adenovirus suppresses the growth of liver cancer cells in vivo and in vitro
Authors: Tian Yufei , Yao Wei , He Dongyun , Xu Yingying , Li Yiquan , Zhu Yilong , Fang Jinbo , Bai Bing , Li Xiao , Sun Lili , Jin Ningyi
Published: October 2019

Oncolytic virus therapy is emerging as important means in cancer treatment. In a previous study, we constructed a dual cancer-specific antitumor recombinant adenovirus, designating it Ad-apoptin-hTERTp-E1a (Ad-VT). This study aimed to investigate the anticancer potential of recombinant adenovirus Ad-apoptin-hTERTp-E1a (Ad-VT) in liver cancer. Crystal Violet staining and CCK-8 assays were used to analyse the inhibitory effect of recombinant adenovirus on human hepatoma cell line QGY-7703 and SMMC-7721. Ad-VT had a significant tumour killing inhibitory effect on QGY-7703 and SMMC-7721 cells that was both dose and a time dependent. Ad-VT-induced apoptosis of QGY-7703 cells was detected using Hoechst, Annexin V, and JC-1 staining, as well as western blotting. Recombinant adenovirus had a strong apoptosis-inducing effect on QGY-7703 cells, and killed QGY-7703 cells mainly through the mitochondrial apoptotic pathway. QGY-7703 cells invasion were detected using cell-scratch and Transwell assays. Recombinant adenovirus could significantly inhibit the invasion of QGY-7703 cells over a short period of time. The pGL4.51 plasmid was used to transfect QGY-7703 cells to construct tumour cells stably expressing luciferase (QGY-7703-LUC). The tumour inhibition effect of Ad-VT in vivo was subsequently confirmed by establishing a tumour-bearing nude mouse model. Ad-VT could effectively inhibit tumour growth and prolong survival of the mice. Recombinant adenovirus Ad-VT has the characteristics of tumour-specific replication and specific tumour killing, and could inhibit the growth of liver cancer QGY-7703 cells and promote their apoptosis.
The Current Status of Cardiovascular and Pulmonary Physical Therapy: An Update of the Description of Specialty Practice
Authors: Rodrigues Jeff , Campbell Angela A. , Frese Ethel , Lowers Sean , Norman Joseph F. , Stackowicz Dawn , Starr Julie , Walko Matthew
Published: October 2019

Purpose:

Cardiopulmonary physical therapy (PT) was one of the first 4 specialty areas recognized within the PT profession in 1978 and was the first to certify specialists in 1985. Physical therapy practice in general and specifically cardiovascular and pulmonary (CVP) PT has expanded over these past 40 years. To maintain currency in this specialty, the American Board of Physical Therapy Specialties (ABPTS) requires that a practice analysis be performed at least every 10 years.

Summary of Key Points:

This article reports the findings of the 2017 practice analysis in CVP PT, resulting in the 2018 version of the Description of Specialist Practice: CVP.

Statement of Conclusion:

This report will serve as the foundation for the examination blueprint for ABPTS board certification in CVP PT, curricula in CVP PT residency programs, activities related to specialist certification, and maintenance of specialist certification.
Biomarkers in Tears and Ocular Surface: A Window for Neurodegenerative Diseases
Authors: Roda Matilde , Ciavarella Carmen , Giannaccare Giuseppe , Versura Piera
Published: October 2019

Objectives:

The purpose of this review is to briefly outline current scientific evidence on the potential role of tear analysis and ocular surface evaluation in diagnosis and monitoring of neurodegenerative diseases, especially Alzheimer disease, Parkinson disease, and glaucoma.

Methods:

A systematic computerized search in the electronic databases PubMed, MEDLINE, and the Cochrane Collaborations was conducted to find eligible articles which their main topic was to investigate the tear and ocular surface in neurodegenerative diseases. After a first screening of titles and abstracts and a full-text review, 26 articles met the inclusion criteria (1 about the neurodegenerative diseases, 3 about the Alzheimer disease, 11 about the Parkinson disease, 11 about glaucoma, and 1 about amyotrophic lateral sclerosis).

Results:

The ocular surface picture seems to be altered in the setting of neurodegenerative diseases with specific characteristics according to each disease. They seem to be associated with reduced corneal sensitivity and abnormal tear function, and each one presents the expression of specific biomarkers in tears.

Conclusions:

The study of tears and ocular surface appears to be a new and noninvasive promising way to assist in the diagnosis and monitoring of neurodegenerative diseases.
Clinical Findings and Ocular Symptoms Over 1 Year in a Sample of Scleral Lens Wearers
Authors: Macedo-de-Araújo Rute J. , Amorim-de-Sousa Ana , van der Worp Eef , González-Méijome José M.
Published: October 2019

Purpose:

To report the fitting aspects, clinical findings, and symptoms over 12 months of scleral lens (SL) wear.

Methods:

Sixty-nine patients with irregular cornea due to ectasia or surgical procedures (IC group) or regular corneas with high ametropia (RC group) completed the 12-month prospective follow-up period. Patients were evaluated at baseline, lens dispensing visit, 1 month, 3 months, 6 months, and 12 months for assessment of comfort, fitting aspects, and slitlamp findings. Comfort was assessed with the Ocular Surface Disease Index (OSDI) questionnaire and Dry Eye Questionnaire. Slitlamp evaluations comprised on-eye lens fitting (lens alignment and tear reservoir thickness) and anterior ocular surface health after removing the lens (edema, hyperemia, staining, and adverse events).

Results:

OSDI Scores were significantly reduced after 1 month of SL wear comparing to baseline (from 47.0±22.7–23.9±14.7 in IC group, P<0.001 and 27.0±16.1–17.0±13.7, P=0.029 in RC group, P<0.05), without statistical significant differences from 1 to 12 months. Tear reservoir thickness showed a significant reduction at V1m (122 μm on IC group and 126 μm in RC group, P<0.05), that continued over time until V12m (195 and 184 μm lower compared with Baseline (P<0.05, Wilcoxon). Hyperemia and staining were significantly higher after SL removal when compared with baseline (P<0.05), and maintained the same behavior over the 12 months. There were no severe adverse events during the entire follow-up period.

Conclusions:

Comfort enhancement promoted by SL remained over the entire follow-up. Despite no severe adverse events recorded over the 12 months of follow-up, higher hyperemia and staining grades were found after SL removal when compared with no-lens condition.
Topical Vancomycin 5% Is More Efficacious Than 2.5% and 1.25% for Reducing Viable Methicillin-Resistant Staphylococcus aureus in Infectious Keratitis
Authors: Romanowski Eric G. , Romanowski John E. , Shanks Robert M. Q. , Yates Kathleen A. , Mammen Alex , Dhaliwal Deepinder K. , Jhanji Vishal , Kowalski Regis P.
Published: October 2019

Purpose:

Topical vancomycin 5% (50 mg/mL) has been used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) keratitis, but patient comfort has many clinicians using lower concentrations. We compared the efficacy of different concentrations of vancomycin in the treatment of experimental MRSA keratitis.

Methods:

The corneas of 45 rabbits were infected with 2000 colony-forming units (CFUs) of MRSA. Corneal epithelium was abraded in the left eyes to mimic corneal ulceration. After 4 hours, the corneal CFUs were determined at the onset of treatment. The remaining rabbits were divided into 4 treatment groups (n = 9): 1) vancomycin 5%, 2) vancomycin 2.5%, 3) vancomycin 1.25%, and 4) saline. The rabbits were treated topically in both eyes every 15 minutes for 5 hours. One hour after treatment, the rabbits were clinically examined and euthanized, corneas were removed, and CFUs were determined to analyze vancomycin penetration, treatment efficacy, and bactericidal effect.

Results:

Ocular toxicity was concentration dependent from mild to moderate. For the abraded corneas, the CFUs of the vancomycin 5% group were lower than 2.5% and 1.25%, and all vancomycin groups were lower than saline. The CFUs of 2.5% were lower but similar to 1.25%. The vancomycin 5% group demonstrated a bactericidal effect and the best penetration. The CFUs of the abraded corneas treated with saline were lower than those of the intact corneas, indicating a possible antibacterial effect from the ocular surface.

Conclusions:

Vancomycin 5% was most potent for treating experimental MRSA keratitis. The clinician may need to reassess treatment regarding antibacterial efficacy and patient comfort.