bluuebunny/crossref_metadata_2025 huggingface dataset:
Punitive Love
Authors: Wessling Jordan
Published: July 2020

While a number of theologians maintain that the motives resting behind God’s love and punitive wrath are often opposed to one another, Chapter 6 argues that God’s just wrath is a facet of His love and that God’s punishment of sinners is an expression of this relentless love. To make this case, it is first contended that God’s creation out of love as well as the ministry of Christ support the notion that God’s love and punitive wrath are fundamentally one. Next, the work of Gregory of Nyssa and the contemporary philosopher R.A. Duff are built upon to construct a communicative model of divine punishment. According to this model, God’s punishment intends to communicate to sinners the censure they deserve, with the aim of persuading these individuals to start down the path of spiritual transformation. In the final section, the communicative theory of divine punishment is applied to the doctrine of hell. There it is suggested that, given the communicative theory, hell is best seen as a place where God tries to reform sinners and enable them to exit hell and join the glorified saints. But, it is shown, this conception of hell does not by itself entail universal salvation.
Trinity, Deification, and Atonement
Authors: Wessling Jordan
Published: July 2020

Chapter 7 proposes a manner of conceiving of God’s deifying love, whereby God shares His intra-trinitarian life of love with men and women through the life and death of Christ. The proposal, which builds upon the Eastern Orthodox distinction between God’s essence and energies, includes partial accounts of both the Atonement and deification, along with an explanation of how these two doctrines fit together. The offered account of God’s deifying love is also shown to fit nicely with the understanding of love’s union exposited and defended in Chapter 2, thereby highlighting a connection between the defended model of God’s love and a classical way of thinking about Christian salvation.
Associations between Amygdala-Prefrontal Functional Connectivity and Age Depend on Neighborhood Socioeconomic Status
Authors: Ramphal Bruce , DeSerisy Mariah , Pagliaccio David , Raffanello Elizabeth , Rauh Virginia , Tau Gregory , Posner Jonathan , Marsh Rachel , Margolis Amy E
Published: July 2020

Although severe early life stress has been shown to accelerate the development of frontolimbic resting-state functional connectivity (RSFC), less is known about the effects of socioeconomic disadvantage, a prolonged and multifaceted stressor. In a cross-sectional study of 127 participants aged 5–25, we examined whether lower neighborhood socioeconomic status (SES; measured by Area Deprivation Index and neighborhood poverty and educational attainment) was associated with prematurely reduced amygdala-ventromedial prefrontal cortex (vmPFC) RSFC. We further tested whether neighborhood SES was more predictive than household SES and whether SES effects on connectivity were associated with anxiety symptoms. We found reduced basolateral amygdala-vmPFC RSFC at earlier ages in participants from more disadvantaged neighborhoods; this effect was unique to neighborhood SES and absent for household SES. Furthermore, this reduced connectivity in more disadvantaged youth and increased connectivity in more advantaged youth were associated with less anxiety; children who deviated from the connectivity pattern associated with their neighborhood SES had more anxiety. These results demonstrate that neighborhood socioeconomic disadvantage is associated with accelerated maturation of amygdala-vmPFC RSFC and suggest that the pathophysiology of pediatric anxiety depends on a child’s neighborhood socioeconomic characteristics. Our findings also underscore the importance of examining SES effects in studies of brain development.
A Kinetic Analysis of DNA-Deoxy Guanine Adducts in the Nasal Epithelium Produced by Inhaled Formaldehyde in Rats—Assessing Contributions to Adduct Production From Both Endogenous and Exogenous Sources of Formaldehyde
Authors: Campbell Jr Jerry L , Gentry P Robinan , Clewell III Harvey J , Andersen Melvin E
Published: July 2020

Although formaldehyde is a normal constituent of tissues, lifetime inhalation exposures at 6 h/day, 5 days/week at concentrations ≥6 ppm caused a nonlinear increase in nasal tumors in rats with incidence reaching close to 50% at 15 ppm. Studies with heavy isotope labeled [13CD2]-formaldehyde permit quantification of both the mass-labeled exogenous and endogenous DNA-formaldehyde reaction products. An existing pharmacokinetic model developed initially to describe 14C-DNA-protein crosslinks (DPX) provided a template for describing the time course of mass-labeled adducts. Published datasets included both DPX and N2-HO13CD2-dG adducts measured after a single 6-h exposure to 0.7, 2, 6, 9, 10, or 15 ppm formaldehyde, after multi-day exposures to 2 ppm for 6 h/day, 7 days/week with interim sacrifices up to 28 days, and after 28-day exposures for 6 h/day, 7 days/week to 0.3, 0.03, or 0.001 ppm. The existing kinetic model overpredicted endogenous adducts in the nasal epithelium after 1-day [13CD2]-formaldehyde exposure, requiring adjustment of parameters for rates of tissue metabolism and background formaldehyde. After refining tissue formaldehyde parameters, we fit the model to both forms of adducts by varying key parameters and optimizing against all 3 studies. Fitting to all these studies required 2 nonlinear pathways—one for high-exposure saturation of clearance in the nasal epithelial tissues and another for extracellular clearance that restricts uptake into the epithelial tissue for inhaled concentrations below 0.7 ppm. This refined pharmacokinetic model for endogenous and exogenous formaldehyde acetal adducts can assist in updating biologically based dose-response models for formaldehyde carcinogenicity.
Application of a Framework for Grouping and Mixtures Toxicity Assessment of PFAS: A Closer Examination of Dose-Additivity Approaches
Authors: Goodrum Philip E , Anderson Janet K , Luz Anthony L , Ansell Graham K
Published: July 2020

Environmental occurrence and biomonitoring data for per- and polyfluoroalkyl substances (PFAS) demonstrate that humans are exposed to mixtures of PFAS. This article presents a new and systematic analysis of available PFAS toxicity study data using a tiered mixtures risk assessment framework consistent with United States and international mixtures guidance. The lines of evidence presented herein include a critique of whole mixture toxicity studies and analysis of dose-response models based on data from subchronic oral toxicity studies in rats. Based on available data to-date, concentration addition and relative potency factor methods are found to be inappropriate due to differences among sensitive effects and target organ potencies and noncongruent dose-response curves for the same effect endpoints from studies using the same species and protocols. Perfluorooctanoic acid and perfluorooctane sulfonic acid lack a single mode of action or molecular initiating event and our evaluation herein shows they also have noncongruent dose-response curves. Dose-response curves for long-chain perfluoroalkyl sulfonic acids (PFSAs) also significantly differ in shapes of the curves from short-chain PFSAs and perfluoroalkyl carboxylic acids evaluated, and additional differences are apparent when curves are evaluated based on internal or administered dose. Following well-established guidance, the hazard index method applied to perfluoroalkyl carboxylic acids and PFSAs grouped separately is the most appropriate approach for conducting a screening level risk assessment for nonpolymeric PFAS mixtures, given the current state-of-the science. A clear presentation of assumptions, uncertainties, and data gaps is needed before dose-additivity methods, including hazard index , are used to support risk management decisions. Adverse outcome pathway(s) and mode(s) of action information for perfluorooctanoic acid and perfluorooctane sulfonic acid and for other nonpolymer PFAS are key data gaps precluding more robust mixtures methods. These findings can guide the prioritization of future studies on single chemical and whole mixture toxicity studies.
Genomes reveal genetic diversity of Piscine orthoreovirus in farmed and free-ranging salmonids from Canada and USA
Authors: Siah A , Breyta R B , Warheit K I , Gagne N , Purcell M K , Morrison D , Powell J F F , Johnson S C
Published: July 2020

Piscine orthoreovirus (PRV-1) is a segmented RNA virus, which is commonly found in salmonids in the Atlantic and Pacific Oceans. PRV-1 causes the heart and skeletal muscle inflammation disease in Atlantic salmon and is associated with several other disease conditions. Previous phylogenetic studies of genome segment 1 (S1) identified four main genogroups of PRV-1 (S1 genogroups I–IV). The goal of the present study was to use Bayesian phylogenetic inference to expand our understanding of the spatial, temporal, and host patterns of PRV-1 from the waters of the northeast Pacific. To that end, we determined the coding genome sequences of fourteen PRV-1 samples that were selected to improve our knowledge of genetic diversity across a broader temporal, geographic, and host range, including the first reported genome sequences from the northwest Atlantic (Eastern Canada). Nucleotide and amino acid sequences of the concatenated genomes and their individual segments revealed that established sequences from the northeast Pacific were monophyletic in all analyses. Bayesian inference phylogenetic trees of S1 sequences using BEAST and MrBayes also found that sequences from the northeast Pacific grouped separately from sequences from other areas. One PRV-1 sample (WCAN_BC17_AS_2017) from an escaped Atlantic salmon, collected in British Columbia but derived from Icelandic broodstock, grouped with other S1 sequences from Iceland. Our concatenated genome and S1 analysis demonstrated that PRV-1 from the northeast Pacific is genetically distinct but descended from PRV-1 from the North Atlantic. However, the analyses were inconclusive as to the timing and exact source of introduction into the northeast Pacific, either from eastern North America or from European waters of the North Atlantic. There was no evidence that PRV-1 was evolving differently between free-ranging Pacific Salmon and farmed Atlantic Salmon. The northeast Pacific PRV-1 sequences fall within genogroup II based on the classification of Garseth, Ekrem, and Biering (Garseth, A. H., Ekrem, T., and Biering, E. (2013) ‘Phylogenetic Evidence of Long Distance Dispersal and Transmission of Piscine Reovirus (PRV) between Farmed and Wild Atlantic Salmon’, PLoS One, 8: e82202.), which also includes North Atlantic sequences from Eastern Canada, Iceland, and Norway. The additional full-genome sequences herein strengthen our understanding of phylogeographical patterns related to the northeast Pacific, but a more balanced representation of full PRV-1 genomes from across its range, as well additional sequencing of archived samples, is still needed to better understand global relationships including potential transmission links among regions.
Association of the 16SrII-D Phytoplasma with African Marigold (Tagetes erecta) Phyllody in Oman
Authors: Al-Subhi Ali M. , Al-Yahyai Rashid A. , Al-Sadi Abdullah M.
Published: July 2020

The African marigold (Tagetes erecta L.) is an ornamental, herbaceous plant commonly found in Oman. In 2019, African marigold plants showing phyllody and virescence symptoms, which are typical symptoms of phytoplasmas disease, were found in at Sultan Qaboos University in Oman. Transmission electron microscopy of marigold leaf midrib from phyllody disease plants showed the presence of numerous phytoplasma bodies in the sieve tube of all of the symptomatic samples. DNA was extracted from asymptomatic and symptomatic marigold plant samples, followed by PCR of the 16S ribosomal RNA (rRNA) and imp genes. The PCR assays showed that the symptomatic plants are positive for phytoplasma. The DNA sequence analysis and phylogenetic trees showed that the 16S rDNA and imp gene sequences from all marigold phyllody strains shared 100% sequence identity to 16SrII-D subgroup sequences in the GenBank. This is the first report of a phytoplasma of the 16SrII-D subgroup associated with the African marigold (T. erecta) worldwide.
Dynamics of Race Structures of Pyricularia oryzae Populations Across 18 Seasons in Guangdong Province, China
Authors: Huang Zhipeng , Wang Jinyan , Zhang Yaling , Yao Yongxiang , Huang Lifei , Yang Xueyan , Wang Ling , Pan Qinghua
Published: July 2020

Rice blast, caused by Pyricularia oryzae, is one of the most damaging fungal diseases affecting rice. Understanding how the pathogen’s race structure varies over time supports the efforts of rice breeders to develop improved cultivars. Here, the race structure of P. oryzae in Guangdong province, China, where rice is cropped twice per year, was assessed over 18 seasons from 1999 through 2008. The analysis was based on the reactions of a panel of seven differential Chinese cultivars to inoculation with a set of 1,248 isolates of P. oryzae in the province. The “total race frequency” parameter ranged from 14.7 to 39.7%, and the “race diversity index” ranged from 0.63 to 0.93. Twelve (ZA63, ZA31, ZA29, ZA21, ZA13, ZA9, ZB30, ZB17, ZB8, ZB2, ZC14, and ZC8) and two (ZD8 and ZD3) races were recognized as specific to indica and japonica rice types, respectively. Of the 59 distinct races identified, only two indica type races (ZC13 and ZC15) were identified as population-common, and nine indica type races (ZB1, ZB5, ZB6, ZB7, ZB13, ZB15, ZC5, ZC13, and ZC15) and one japonica type race (ZG1) were deemed to be population-dominant; the “total top two race isolate frequency” parameter ranged from 29.8 to 74.5%. On the host side, dynamics of resistance structures of the differential set were divided into three patterns: Both Tetep and Kanto 51 expressed the highest and most stable resistance, both Sifeng 43 and Lijiangxintuanheigu conveyed much lower and unstable resistance, and Zhenlong 13, Dongnong 363, and Heijiang 18 performed intermediate and seasonally dynamic resistance. Three interesting points distinguishing race structures of P. oryzae populations in southern and northeastern China were also discussed.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Proteomics Reveals the Changes that Contribute to Fusarium Head Blight Resistance in Wheat
Authors: Yang Mingming , Wang Xianguo , Dong Jian , Zhao Wanchun , Alam Tariq , Thomashow Linda S. , Weller David M. , Gao Xiang , Rustgi Sachin , Wen Shanshan
Published: July 2020

Fusarium head blight (FHB) is a devastating disease of wheat, causing yield losses and quality reduction as a result of mycotoxin production. In this study, iTRAQ (isobaric tags for relative and absolute quantification)-labeling-based mass spectrometry was employed to characterize the proteome in wheat cultivars Xinong 538 and Zhoumai 18 with contrasting levels of FHB resistance as a means to elucidate the molecular mechanisms contributing to FHB resistance. A total of 13,669 proteins were identified in the two cultivars 48 h after Fusarium graminearum inoculation. Among these, 2,505 unique proteins exclusively accumulated in Xinong 538 (resistant) and 887 proteins in Zhoumai 18 (susceptible). Gene Ontology enrichment analysis showed that most differentially accumulated proteins (DAPs) from both cultivars were assigned to the following categories: metabolic process, single-organism process, cellular process, and response to stimulus. Kyoto Encyclopedia of Genes and Genomes analysis showed that a greater number of proteins belonging to different metabolic pathways were identified in Xinong 538 compared with Zhoumai 18. Specifically, DAPs from the FHB-resistant cultivar Xinong 538 populated categories of metabolic pathways related to plant–pathogen interaction. These DAPs might play a critical role in defense responses exhibited by Xinong 538. DAPs from both genotypes were assigned to all wheat chromosomes except chromosome 6B, with approximately 30% mapping to wheat chromosomes 2B, 3B, 5B, and 5D. Twenty single nucleotide polymorphism markers, flanking DAPs on chromosomes 1B, 3B, 5B, and 6A, overlapped with the location of earlier mapped FHB-resistance quantitative trait loci. The data provide evidence for the involvement of several DAPs in the early stages of the FHB-resistance response in wheat; however, further functional characterization of candidate proteins is warranted.
EBP 2.0: Implementing and Sustaining Change: Implementing Improved Central Line Flushing Practices
Authors: Hanrahan Kirsten , Utech Jane , Cullen Laura , Tucker Sharon J. , Gallagher-Ford Lynn
Published: July 2020

This is the eighth article in a series about evidence-based practice (EBP) that builds on AJN's award-winning previous series—Evidence-Based Practice, Step by Step—published between 2009 and 2011 (to access the series, go to http://links.lww.com/AJN/A133). This follow-up series features exemplars illustrating the various strategies that can be used to implement EBP changes—one of the most challenging steps in the EBP process.
Are We Measuring What Matters? How Student and Clerkship Characteristics Influence Clinical Grading
Authors: Ingram Mary A. , Pearman Joseph L. , Estrada Carlos A. , Zinski Anne , Williams Winter L.
Published: July 2020

Purpose

Given the growing emphasis placed on clerkship performance for residency selection, clinical evaluation and its grading implications are critically important; therefore, the authors conducted this study to determine which evaluation components best predict a clinical honors recommendation across 3 core clerkships.

Method

Student evaluation data were collected during academic years 2015–2017 from the third-year internal medicine (IM), pediatrics, and surgery clerkships at the University of Alabama at Birmingham School of Medicine. The authors used factor analysis to examine 12 evaluation components (12 items), and they applied multilevel logistic regression to correlate evaluation components with a clinical honors recommendation.

Results

Of 3,947 completed evaluations, 1,508 (38%) recommended clinical honors. The top item that predicted a clinical honors recommendation was clinical reasoning skills for IM (odds ratio [OR] 2.8; 95% confidence interval [CI], 1.9 to 4.2; P < .001), presentation skills for surgery (OR 2.6; 95% CI, 1.6 to 4.2; P < .001), and knowledge application for pediatrics (OR 4.8; 95% CI, 2.8 to 8.2; P < .001). Students who spent more time with their evaluators were more likely to receive clinical honors (P < .001), and residents were more likely than faculty to recommend clinical honors (P < .001). Of the top 5 evaluation items associated with clinical honors, 4 composed a single factor for all clerkships: clinical reasoning, knowledge application, record keeping, and presentation skills.

Conclusions

The 4 characteristics that best predicted a clinical honors recommendation in all disciplines (clinical reasoning, knowledge application, record keeping, and presentation skills) correspond with traditional definitions of clinical competence. Structural components, such as contact time with evaluators, also correlated with a clinical honors recommendation. These findings provide empiric insight into the determination of clinical honors and the need for heightened attention to structural components of clerkships and increased scrutiny of evaluation rubrics.
A Philosophical Analysis of Spiritual Coping
Authors: Dunn Karen S. , Robinson-Lane Sheria G.
Published: July 2020

Utilizing Whall and associates' philosophical analysis method, the concept of spiritual coping was critically evaluated to determine the relevance of this concept to nursing science. Studies were included in the literature review if participants were 55 years and older, as this cohort has reported using more spiritual coping strategies than younger cohorts. Twenty-four articles were reviewed and revealed 3 recurrent themes: enhanced physical, psychological, and social well-being, resilience, and self-transcendence. Support for the relevance of spiritual coping to nursing science was found, as these themes were easily placed within the context of 3 postmodern philosophical approaches and multiple extant nursing theories.
Pharmacokinetic Variability During Long-Term Therapeutic Drug Monitoring of Valproate, Clobazam, and Levetiracetam in Patients With Dravet Syndrome
Authors: Johannessen Landmark Cecilie , Heger Katrine , Lund Caroline , Burns Margrete Larsen , Bjørnvold Marit , Sætre Erik , Johannessen Svein I.
Published: July 2020

Background:

The use of therapeutic drug monitoring (TDM) for antiseizure medications (ASMs) may contribute to treatment optimization in individual patients. This study included patients with Dravet syndrome as they often require close monitoring because of polypharmacy with various ASMs. The aim was to use long-term TDM to investigate pharmacokinetic variability of ASMs in these patients.

Methods:

Retrospective data from patients with Dravet syndrome were collected from the TDM database at the Section for Clinical Pharmacology, National Center for Epilepsy in Norway (2008–2018). Concentration/(dose/kg)ratios (C/D ratios) were calculated for the ASMs and the concentration (C/C ratio) for N-desmethylclobazam. In patients with at least 3 measurements, the CV for C/D ratios for intrapatient and interpatient variability was calculated.

Results:

Fifty-three patients (30 male patients/23 female patients) between 2 and 50 years of age (mean, 16 years) were included. Pharmacokinetic variability of the total number of measurements of valproate (n = 417), clobazam and N-desmethylclobazam (n = 328), and levetiracetam (n = 238) was determined. Interpatient variability was more pronounced than intrapatient variability (coefficient of variations: valproate, 65% vs. 24%; levetiracetam, 71% vs. 27%; and clobazam/N-desmethylclobazam, 47%/77% vs. 35%/55%) (P < 0.01). Comedication with stiripentol (n = 16) increased the C/D ratio of valproate by 63% and of clobazam by 133% and the C/C ratio of N-desmethylclobazam/clobazam by 104% (P < 0.05). Younger age also contributed to pharmacokinetic variability.

Conclusions:

Long-term TDM revealed extensive variability in serum concentrations over time; the variability was lowest for levetiracetam, moderate for valproate, and highest for clobazam. Pharmacokinetic variability and interactions can thus be identified and adjusted to facilitate decision making to achieve the optimal treatment outcome.
Therapeutic Drug Monitoring of Antidepressants for the Treatment of Chronic Musculoskeletal Pain With and Without Depression
Authors: Scherf-Clavel Maike , Breisinger Sarah , Fischer Monika , Deckert Jürgen , Unterecker Stefan , Rittner Heike L.
Published: July 2020

Background:

Antidepressants are recommended for the treatment of chronic musculoskeletal pain; however, target serum concentrations based on therapeutic drug monitoring (TDM) have not been established. Therefore, the authors analyzed routine care TDM data of antidepressants in patients with chronic pain with and without depression in terms of treatment outcomes in an interdisciplinary multimodal pain treatment (IMPT) program.

Methods:

Patients with chronic musculoskeletal pain and TDM for amitriptyline (n = 45) or duloxetine (n = 30) were retrospectively included. The German pain questionnaire for pain intensity and the Depression Anxiety Stress scale were applied at T0 and at the end of the IMPT program (T1). A relief of pain intensity score ≥2 was considered as a positive outcome. Comorbid depression was diagnosed based on ICD-10 criteria. Serum concentrations of antidepressants were measured for routine clinical care TDM.

Results:

After IMPT, stress improved in all subgroups, and depressive symptoms improved only in the duloxetine group. Overall, 40% and 27% of patients in the amitriptyline and duloxetine subgroup, respectively, were responders in terms of maximum pain score relief. Responders with comorbid depression were treated with a dose that led to a 1.7-fold higher serum concentration of the active moiety of amitriptyline (amitriptyline + nortriptyline) compared with nonresponders. Similarly, a 2.3-fold higher serum concentration was observed in depressed responders than in nondepressed responders (at minimum 131.5 ng/mL).

Conclusions:

Dosing of antidepressants for chronic pain relief should specifically take comorbid depression into account. TDM may provide better outcomes of pain relief in an IMPT setting in patients with comorbid depression.
Immunosuppressive Drug-Associated Adverse Event Profiles in De Novo Kidney Transplant Recipients Receiving Everolimus and Reduced Tacrolimus Doses
Authors: Miranda Tamiris A. , Felipe Claudia R. , Santos Renato H. N. , Medina Pestana Jose O. , Tedesco-Silva Junior Helio
Published: July 2020

Background:

The safety of immunosuppressive regimens is influenced by the induction agent, maintenance drug combination, and prophylactic strategy for cytomegalovirus (CMV) infection. Herein, this safety analysis compares rabbit antithymocyte globulin (r-ATG) or basiliximab (BAS) combined with everolimus (EVR) versus BAS combined with mycophenolate sodium (MPS) in kidney transplant recipients receiving tacrolimus, prednisone, and preemptive CMV therapy.

Methods:

In this single-center, prospective, randomized study, adverse events (AEs), serious AEs (SAEs), viral infections, laboratory abnormalities, dose reductions, and temporary or permanent discontinuation of the immunosuppressant were compared among patients receiving r-ATG/EVR (n = 85), BAS/EVR (n = 102), and BAS/MPS (n = 101).

Results:

A total of 2741 AEs and 344 SAEs were observed. There were no differences in the proportion of patients with at least one AE (96% versus 98% versus 96%, respectively; P > 0.05). The proportion of patients with at least one SAE was highest in the BAS/MPS group (33% versus 48% versus 69%, respectively; P < 0.05). This difference was due primarily to a high incidence of CMV infection in the BAS/MPS group (4.7% versus 10.8% versus 37.6%, respectively). The incidence of mild/moderate abnormalities in creatinine, cholesterol, and triglyceride levels was higher in both EVR groups. The cumulative freedom from dose reduction or treatment discontinuation due to an AE was higher in both EVR groups than in the BAS/MPS group (89.2% versus 92.8% versus 76.3%, respectively, P = 0.003). There was no difference in the incidence of biopsy-confirmed acute rejection (9.4% versus 18.6 versus 15.8%, respectively; P = 0.403).

Conclusions:

This analysis suggests that r-ATG induction combined with EVR is associated with a comparable incidence of acute rejection, lower incidence of CMV infection, and fewer changes in initial immunosuppressive regimen due to AEs in kidney transplant recipients receiving tacrolimus, prednisone, and preemptive CMV therapy.
ASSOCIATION BETWEEN DOME-SHAPED MACULA AND POSTERIOR STAPHYLOMA IN HIGHLY MYOPIC EYES INVESTIGATED BY ULTRA-WIDEFIELD OPTICAL COHERENCE TOMOGRAPHY
Authors: Saito Reina , Shinohara Kosei , Tanaka Noriko , Takahashi Hiroyuki , Yoshida Takeshi , Ohno-Matsui Kyoko
Published: July 2020

Purpose:

To investigate the relationship between dome-shaped maculas (DSMs) and posterior staphylomas in highly myopic eyes.

Methods:

Five hundred and eleven eyes of 291 patients with high myopia (refractive error ≤−8.0 diopters or axial length ≥26.5 mm) were examined by ultra-widefield swept-source optical coherence tomography (UWF-OCT). Posterior staphylomas were identified by detecting the staphyloma edges in the UWF-OCT images.

Results:

Eighty-two eyes of the 511 highly myopic eyes had a DSM, and a posterior staphyloma was observed in 45 of 82 eyes with a DSM (54.9%) and in 301 of 429 eyes (70.2%) without a DSM. The incidence of staphylomas was significantly lower in eyes with a DSM than those without a DSM (P = 0.007). The wide macular type of staphyloma was the predominant type in eyes with a DSM (31/45 eyes; 68.9%), whereas the narrow macular type and wide macular type of staphylomas were present almost equally in the eyes without a DSM.

Conclusion:

The lack of staphylomas in 45% of eyes with a DSM suggests that DSMs form independently from posterior staphylomas. Dome-shaped maculas tend to occur in eyes with a large expansion of the posterior fundus and should be considered a posterior scleral curvature abnormality.
The Effects of Nicotine on Cortical Excitability After Exercise
Authors: Zandonai Thomas , Pizzolato Fabio , Tam Enrico , Bruseghini Paolo , Chiamulera Cristiano , Cesari Paola
Published: July 2020

Purpose

The use of smokeless tobacco/nicotine products is common among athletes, but clear evidence for their positive or negative effect on sports performance is lacking. Nicotine is a psychoactive substance involved in numerous neuronal processes including cortical excitability. The aim of this study was to evaluate its effect on cortical excitability associated with aerobic exercise in nicotine-naive healthy volunteers.

Methods

Ten nicotine-naive healthy volunteers were recruited for this double-blind, randomized, crossover study to compare the effect of snus (8 mg nicotine), an oral, smokeless tobacco product, to placebo on cortical excitability before and after aerobic exercise. Transcranial magnetic stimulation (TMS) was used to measure changes in corticomotor excitability (motor-evoked potentials, MEPs) and electromyography of leg muscles during maximal voluntary contractions (MVC) to assess changes in muscle contractions. Before and after aerobic exercise and with or without nicotine treatment, MEPs and MVCs were measured.

Results

Analysis of TMS data showed lower motor cortex activation (lower MEP amplitude) after snus administration compared with placebo, whereas electromyography data showed no difference in muscle contraction between snus and placebo treatment.

Conclusions

These findings suggest a general reduction in cortical excitability, without no relevant effect on physical performance.
Mean arterial pressure and arterial stiffness in Japanese population: a secondary analysis based on a cross-sectional study
Authors: Sheng Song
Published: July 2020

Previous researches demonstrate that mean arterial pressure (MAP) is associated with major cardiovascular events, but there are few research on the correlation between MAP and brachial-ankle pulse wave velocity (BaPWV). Thus, the present study is designated to examine the association between MAP and BaPWV. Our study is a cross-sectional study in Japanese. They participated in a medical check-up program which included BaPWV and standardized questionnaires. The main measurements include systolic blood pressure, diastolic blood pressure, BaPWV, ankle-brachial index (ABI), fatty liver diagnosed by ultrasonography, etc. It needs to be emphasized that Fukuda et al. finished the study and their data are used for secondary analysis. MAP is positively related with BaPWV [effect size = 10.4; 95% confidence interval (CI), 9.2–11.6] after adjusting age, sex, BMI, smoking status, alcohol consumption, exercise, glutamyltranspeptidase, alanine aminotransferase, aspartate transaminase, total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein cholesterol (HDL), fatty liver, fasting-blood glucose, uric acid, estimated glomerular filtration rate, and ABI. The nonlinear association is identified between MAP and BaPWV whose inflection point is 94 mmHg. The effect size and 95% CI on the bilateral sides of the inflection point are 8.0 (4.4–11.6) and 14.8 (12.5–17.1), respectively. Subgroup analysis indicates that MAP has a more significantly positive association with BaPWV in ex-smokers, old people (age ≥60), and participants with lower HDL (<40 mg/dL). Consequently, it is practicable for us to roughly predict BaPWV with simple MAP measurement instead of the BaPWV examination.
Advances in lung transplantation for interstitial lung diseases
Authors: De Sadeleer Laurens J. , Verleden Stijn E. , Vos Robin , Van Raemdonck Dirk , Verleden Geert M.
Published: July 2020

Purpose of review

Lung transplantation (LTx) is increasingly used as ultimate treatment modality in end-stage interstitial lung diseases (ILDs). This review aims to give an overview of the latest evolutions in this field.

Recent findings

In the last two years, important new findings regarding LTx outcomes in specific ILD entities have been reported. More data are available on optimization of pre-LTx management of ILD patients especially with regard to pretransplant antifibrotic treatment.

LTx is the only treatment option with curative intent for ILDs and is increasingly used for this indication. Several studies have now reported adequate outcomes in different ILD entities, although outcome is shown to be affected by underlying telomeropathies. As new studies could not replicate inferior survival with single compared with double LTx, both options remain acceptable. ILD specialists can beneficially impact on post-LTx outcome by optimizing pre-LTx management: corticosteroids should be avoided, antifibrotics should be initiated whenever possible and BMI and nutritional status optimized, rehabilitation and depression-screening strategies should be implemented in all LTx candidates, as these interventions may all improve postlung transplant survival.
Recent advances in sarcoidosis genomics: epigenetics, gene expression, and gene by environment (G × E) interaction studies
Authors: Garman Lori , Montgomery Courtney G. , Rivera Natalia V.
Published: July 2020

Purpose of review

We aim to review the most recent findings in genomics of sarcoidosis and highlight the gaps in the field.

Recent findings

Original explorations of sarcoidosis subphenotypes, including cases associated with the World Trade Center and ocular sarcoidosis, have identified novel risk loci. Innovative gene--environment interaction studies utilizing modern analytical techniques have discovered risk loci associated with smoking and insecticide exposure. The application of whole-exome sequencing has identified genetic variants associated with persistent sarcoidosis and rare functional variations. A single epigenomics study has provided background knowledge of DNA methylation mechanisms in comparison with gene expression data. The application of machine-learning techniques has suggested new drug repositioning for the treatment of sarcoidosis. Several gene expression studies have identified prominent inflammatory pathways enriched in the affected tissue.

Certainly, sarcoidosis research has recently advanced in the exploration of disease subphenotypes, utilizing novel analytical techniques, and including measures of clinical variation. Nevertheless, large-scale and diverse cohorts investigated with advanced sequencing methods, such as whole-genome and single-cell RNA sequencing, epigenomics, and meta-analysis coupled with cutting-edge analytic approaches, when employed, will broaden and translate genomics findings into clinical applications, and ultimately open venues for personalized medicine.
Updates in diagnosis of the inherited platelet disorders
Authors: Lambert Michele P.
Published: July 2020

Purpose of review

To provide a comprehensive update on the current available methodologies and techniques for diagnosis of inherited platelet disorders (IPD).

Recent findings

The contributions of many groups have resulted in the significant progress in the molecular diagnosis of IPD including the identification of many genes responsible for the various phenotypes. The widespread use and availability of next-generation sequencing has brought to the forefront ethical challenges associated with nontargeted sequencing as well as provided us with novel variants to functionally validate. These requirements have driven the development of novel tools for functional assessment of platelets, although none of the novel techniques beyond sequencing have yet taken clinical hold.

Much work is ongoing on functional and molecular assessment of platelet disorders and the incorporation of combined assessments is likely to yield the highest diagnostic results.
Cardiac Myxoma: Review and Update of Contemporary Immunohistochemical Markers and Molecular Pathology
Authors: Velez Torres Jaylou M. , Martinez Duarte Ernesto , Diaz-Perez Julio A. , Rosenberg Andrew E.
Published: July 2020

Cardiac myxoma is an uncommon benign mesenchymal neoplasm of the heart. It usually arises in the left atrium, near the valve of the fossa ovalis, and most frequently affects adults in the third through the sixth decades of life. It is hypothesized to arise from subendothelial vasoformative reserve cells or primitive cells that differentiate along the lines of the endothelium, but this remains speculative. Microscopically, the neoplastic cells are arranged individually, and nests, and are oriented in single or multiple layers around vascular channels. The neoplastic cells are immunoreactive for vimentin, calretinin, S100, nonspecific enolase, factor VIII, CD31, and CD34. The tumor can have diverse clinical presentations depending on its location and extent of disease and is predisposed to embolization. The current treatment is prompt surgical excision.
Histopathologic and Autopsy Findings in Patients Diagnosed With Coronavirus Disease 2019 (COVID-19): What We Know So Far Based on Correlation With Clinical, Morphologic and Pathobiological Aspects
Authors: Al Nemer Areej
Published: July 2020

In response to the current outbreak of Coronavirus Disease-2019 (COVID-19), a fast body of literature emerged providing insights into the clinical and radiologic aspects of the novel disease, while the pathologic manifestations on tissue are yet to be sufficiently characterized mainly due to paucity of autopsy and biopsy of these cases. It is essential for both the clinicians and pathologists to maintain up-to-date knowledge of this continuously evolving topic in the midst of the current pandemic. Besides, understanding the impact of any disease in tissue pathology is crucial for better analysis of the pathogenesis and speculation of potential therapeutic targets. This review aimed to highlight the potential implication of COVID-19 in the pathology of various organ systems. We discuss the pathologic findings of the lungs, gastrointestinal tract, liver, brain, kidneys, heart, and the reproductive and immune systems that are associated with COVID-19. It seems that the respiratory, immune, and the digestive systems are the major targets of the disease. Mild mononuclear inflammatory cell infiltration is the most frequent histologic finding in general. Besides organ-specific changes, microthrombi, especially noticed in lungs, kidneys, and prostates, are the most significant observation microscopically. In addition, the possible mechanisms of organ injury were also reviewed.
Diagnosing and Managing Sacroiliac Joint Pain
Authors: Gusfa Donald , Bashir Daniyal A. , Saffarian Mathew R.
Published: July 2020

Sacroiliac joint pain commonly occurs because of anatomic disruption within the joint. Sacroiliac joint pain and sacroiliac joint mimics create a broad differential, adding difficulty to diagnosis. Clinically, this disruption presents with a mobility limitation relative to baseline and sharp pain inferolateral to the posterior superior iliac spine. While attempting to rule out other causes of low back pain, provocation tests such as FABRE, distraction, thigh thrust, sacral compression, Gaenslen’s, and sacral thrust can be a useful diagnostic tool for the diagnosis of sacroiliac joint pain. Although recently, the provocation tests’ validity has been challenged. Currently, the most accurate way to assess sacroiliac joint pain is with image-guided injections of local anesthetic. Pain reduction after the injection indicates the pain originating from the sacroiliac joint. Once confirmed, it is recommended to use a patient-centered approach that focuses on pain control, followed by restoration of function through noninvasive measures such as therapeutic exercise, manual medicine, sacroiliac joint belts, and orthotics. If these noninvasive procedures have not provided adequate treatment, then more invasive procedures should be considered.
Price, Cost, and Value of Cancer Medicines
Authors: Rothenberg Mace L. , McCarthy Justin , Holmes Patrick
Published: July 2020

More than 1.8 million cancer diagnoses will be made in 2020 driving substantial health and economic burden for patients. The financial impact of out-of-pocket payments for hospital stays, outpatient services, physician appointments, and prescription drugs is a particular challenge. At the same time, the treatment of cancer is undergoing substantial transformation with growing benefits for patients. The complex factors contributing to the economic burden must be addressed so that patients have broad access to innovative oncology medicines both today and tomorrow. There are 2 parallel actions that are needed to drive broad reductions in costs while not putting at risk the incredible potential innovation awaiting these same patients: (i) the private sector must work together across the health care sector to accelerate innovative value-based partnerships; and (2) policymakers need to drive policy reforms that help ease out-of-pocket costs and remove barriers to and enable scaling of value-based care.
Bending Versus Transforming the Drug Cost Curve
Authors: Major Ajay , Polite Blase N.
Published: July 2020

There is increasing consensus that comprehensive reforms are needed to curb the rising costs of specialty drugs and growing bipartisan agreement on the basic principles that these reforms must address (1) constraints on yearly inflation of drug prices, (2) limits on practices to extend patents and restrict generic competition, (3) increased transparency of rebates provided by pharmaceutical companies to pharmacy benefit managers and insurance companies, and (4) caps on the total yearly out-of-pocket costs for Medicare patients. While such reforms will improve the current system, they are unlikely to be truly transformative. Transformative change requires that all the relevant stakeholders be forced, by a legislative or administrative mandate, to come to an agreement on value. Whether federal policy makers have the will to do so will determine whether we truly change the trajectory of the currently unsustainable drug cost curve.
Marginal Zone Lymphomas
Authors: Bertoni Francesco , Rossi Davide , Raderer Markus , Zucca Emanuele
Published: July 2020

There are three different marginal zone lymphoma (MZLs) entities: the extranodal MZL of mucosa- associated lymphoid tissue, the splenic MZL, and the nodal MZL. The 3 MZLs share common lesions (trisomies of chromosomes 3 and 18, deletions at 6q23), and alterations of the nuclear factor κB pathway are frequent events in all of them, but they also differ in the presence of recurrent translocations, mutations affecting the NOTCH pathway, and the transcription factor Kruppel-like factor 2 (KLF2)or the receptor-type protein tyrosine phosphatase delta (PTPRD). This review outlines the most recent and main advances in our understanding of the genetics and biology of MZLs and summarizes the clinical activity of the novel therapeutic approaches targeting the main druggable pathways. The current principles of the standard management of MZL at different anatomic sites are also discussed.
Improving Patient Handoffs and Transitions through Adaptation and Implementation of I-PASS Across Multiple Handoff Settings
Authors: Blazin Lindsay J. , Sitthi-Amorn Jitsuda , Hoffman James M. , Burlison Jonathan D.
Published: July 2020

Introduction:

Communication failures are common root causes of serious medical errors. Standardized, structured handoffs improve communication and patient safety. I-PASS is a handoff program that decreases medical errors and preventable patient harm. The I-PASS mnemonic is defined as illness severity, patient information, action list, situational awareness and contingency plans, and synthesis by receiver. I-PASS was validated for physician handoffs, yet has the potential for broader application. The objectives of this quality improvement initiative were to adapt and implement I-PASS to handoff contexts throughout a pediatric hospital, including those with little or no known evidence of using I-PASS.

Methods:

We adapted and implemented I-PASS for inpatient nursing bedside report, physician handoff, and imaging/procedures handoff. Throughout the initiative, end-user stakeholders participated as team members and informed the adaptation of the I-PASS mnemonic, handoff processes, written handoff documents, and performance evaluation methods. Peers observed handoffs, scored performance, and provided formative feedback. Adherence to I-PASS was the primary outcome. We also evaluated changes in handoff-related error frequency and clinician attitudes about the effects of I-PASS on personal and overall handoff performance.

Results:

All 5 elements of the I-PASS mnemonic were used in 87% of inpatient nursing, 76% of physician, and 89% of imaging/procedures handoffs. Inpatient nurses reported reductions in handoff-related errors following I-PASS implementation. Clinicians across most handoff settings reported that using I-PASS improved both general and personal handoff performance.

Conclusions:

I-PASS is adaptable to many handoff settings, which expands its potential to improve patient safety. Clinicians reported reductions in errors and improvements in handoff performance. We identified broad institutional support, customized written handoff documents, and peer observations with feedback as crucial factors in sustaining I-PASS usage.
HIV and risk of dementia in older veterans
Authors: Bobrow Kirsten , Xia Feng , Hoang Tina , Valcour Victor , Yaffe Kristine
Published: July 2020

Objective:

People living with HIV (PLWH) may be at an increased risk for dementia as they age. Surprisingly, it remains unclear whether PLWH have a higher risk of developing dementia in late life than those without. We explored whether HIV-infection is associated with incident dementia diagnosis in older U.S. veterans accounting for potential confounders and competing risk of death.

Methods:

We included 1114 veterans diagnosed with HIV, ages at least 55 years (mean = 62 years, SD = 6), followed in the Veterans Health Administration healthcare system from 2004 to 2015, and a propensity-matched comparison group (n = 1114) without HIV. HIV and dementia diagnoses were determined using electronic medical records. Using Fine-Gray proportional hazards models, we examined whether HIV status was associated with a greater risk of incident dementia.

Results:

During follow-up (mean = 7 years, SD = 4 from date of HIV diagnosis), 5% of veteran PLWH developed dementia compared with 3% without (P = 0.01). Accounting for the competing risk of death and adjusted for demographics, substance use, education and income, PLWH remained 50% more likely to receive a dementia diagnosis [adjusted hazard ratio (aHR) = 1.50, 95% confidence interval 0.96–2.35]. Although combination antiretroviral therapy (cART) exposure was associated with an increased risk of incident dementia, this was driven by differences in illness severity as captured by CD4+ cell count. There was no evidence of a differential effect by cART class.

Conclusion:

In a cohort of older USA veterans, HIV infection increased risk of dementia by 50%, while exposure to cART did not offset this risk. It is critical to understand the mechanisms by which HIV increases risk for developing dementia in later life.
The role of barriers to care on the propensity for hepatitis C virus nonreferral among people living with HIV
Authors: Cachay Edward R. , Torriani Francesca J. , Hill Lucas , Jain Sonia , Del Real Azucena , Qin Huifang , Martin Natasha , Mathews William C.
Published: July 2020

Twenty-five percent of HIV/hepatitis C virus (HCV) coinfected patients were not referred for HCV treatment despite unrestricted access in California to direct-acting antivirals (DAA) in 2018. Having unstable housing and ongoing drug use directly affected HCV treatment nonreferral. However, psychiatric history and alcohol use impacted HCV treatment nonreferral through the mediation of not being engaged in HIV care. Achieving HCV elimination requires DAA treatment outside conventional health settings, including substance rehabilitation centers, mental health crisis houses, and homeless shelters.