bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid activation of tumor-associated macrophages boosts preexisting tumor immunity
Authors: Hoves Sabine , Ooi Chia-Huey , Wolter Carsten , Sade Hadassah , Bissinger Stefan , Schmittnaegel Martina , Ast Oliver , Giusti Anna M. , Wartha Katharina , Runza Valeria , Xu Wei , Kienast Yvonne , Cannarile Michael A. , Levitsky Hyam , Romagnoli Solange , De Palma Michele , Rüttinger Dominik , Ries Carola H.
Published: February 2018

Depletion of immunosuppressive tumor-associated macrophages (TAMs) or reprogramming toward a proinflammatory activation state represent different strategies to therapeutically target this abundant myeloid population. In this study, we report that inhibition of colony-stimulating factor-1 receptor (CSF-1R) signaling sensitizes TAMs to profound and rapid reprogramming in the presence of a CD40 agonist before their depletion. Despite the short-lived nature of macrophage hyperactivation, combined CSF-1R+CD40 stimulation of macrophages is sufficient to create a proinflammatory tumor milieu that reinvigorates an effective T cell response in transplanted tumors that are either responsive or insensitive to immune checkpoint blockade. The central role of macrophages in regulating preexisting immunity is substantiated by depletion experiments, transcriptome analysis of ex vivo sorted TAMs, and gene expression profiling of whole tumor lysates at an early treatment time point. This approach enabled the identification of specific combination-induced changes among the pleiotropic activation spectrum of the CD40 agonist. In patients, CD40 expression on human TAMs was detected in mesothelioma and colorectal adenocarcinoma.
A kinetic account for amphetamine-induced monoamine release
Authors: Hasenhuetl Peter S. , Bhat Shreyas , Mayer Felix P. , Sitte Harald H. , Freissmuth Michael , Sandtner Walter
Published: February 2018

The plasmalemmal monoamine transporters for dopamine, norepinephrine, and serotonin (SERT) are targets for amphetamines. In vivo, amphetamines elicit most, if not all, of their actions by triggering monoamine efflux. This is thought to be accomplished by an amphetamine-induced switch from the forward-transport to the substrate-exchange mode. The mechanism underlying this switch has remained elusive; available kinetic models posit that substrates and cosubstrate Na+ ions bind either in a random or in a sequential order. Neither can account for all reported experimental observations. We used electrophysiological recordings to interrogate crucial conformational transitions associated with the binding of five different substrates (serotonin, para-chloroamphetamine, and the high-affinity naphthyl-propan-amines PAL-287, PAL-1045, and PAL-1046) to human SERT expressed in HEK293 cells; specifically, we determined the relaxation kinetics of SERT from a substrate-loaded to a substrate-free state at various intracellular and extracellular Na+ concentrations. These rates and their dependence on intracellular and extracellular Na+ concentrations differed considerably between substrates. We also examined the effect of K+ on substrate affinity and found that K+ enhanced substrate dissociation. A kinetic model was developed, which allowed for random, but cooperative, binding of substrate and Na+ (or K+). The synthetic data generated by this model recapitulated the experimental observations. More importantly, the cooperative binding model accounted for the releasing action of amphetamines without any digression from alternating access. To the best of our knowledge, this model is the first to provide a mechanistic framework for amphetamine-induced monoamine release and to account for the findings that some substrates are less efficacious than others in promoting the substrate-exchange mode.
SEED 2: a user-friendly platform for amplicon high-throughput sequencing data analyses
Authors: Větrovský Tomáš , Baldrian Petr , Morais Daniel
Published: February 2018

Motivation

Modern molecular methods have increased our ability to describe microbial communities. Along with the advances brought by new sequencing technologies, we now require intensive computational resources to make sense of the large numbers of sequences continuously produced. The software developed by the scientific community to address this demand, although very useful, require experience of the command-line environment, extensive training and have steep learning curves, limiting their use. We created SEED 2, a graphical user interface for handling high-throughput amplicon-sequencing data under Windows operating systems.

Results

SEED 2 is the only sequence visualizer that empowers users with tools to handle amplicon-sequencing data of microbial community markers. It is suitable for any marker genes sequences obtained through Illumina, IonTorrent or Sanger sequencing. SEED 2 allows the user to process raw sequencing data, identify specific taxa, produce of OTU-tables, create sequence alignments and construct phylogenetic trees. Standard dual core laptops with 8 GB of RAM can handle ca. 8 million of Illumina PE 300 bp sequences, ca. 4 GB of data.

Availability and implementation

SEED 2 was implemented in Object Pascal and uses internal functions and external software for amplicon data processing. SEED 2 is a freeware software, available at http://www.biomed.cas.cz/mbu/lbwrf/seed/ as a self-contained file, including all the dependencies, and does not require installation. Supplementary data contain a comprehensive list of supported functions.

Supplementary information

Supplementary data are available at Bioinformatics online.
Quality of Life After Motor Cortex Stimulation: Clinical Results and Systematic Review of the Literature
Authors: Parravano Daniella C , Ciampi Daniel A , Fonoff Erich T , Monaco Bernardo , Navarro Jessie , Yeng Lin T , Teixeira Manoel J , Hamani Clement
Published: February 2018

BACKGROUND

Motor cortex stimulation (MCS) is routinely used for the treatment of chronic neuropathic pain but its effect on quality of life remains uncertain.

OBEJCTIVE

To systematically review the published literature on MCS and quality of life and report the effects of this therapy in a series of patients prospectively followed in our center.

METHODS

The systematic literature review was conducted using the search words “motor cortex stimulation and pain and neurosurgery” and “motor cortex stimulation and pain and quality of life.” Quality of life in our clinical trial was investigated in a series of 10 patients with chronic neuropathic pain prospectively followed for 12 mo after MCS.

RESULTS

Two hundred eighteen nonreplicated articles were pooled for analysis. Of these, 6 described measures of quality of life in the pre- and postoperative period. In these studies, 64 patients with different clinical conditions associated with neuropathic pain were followed for 6 to 84 mo after MCS surgery. Improvement in quality of life ranged from 35% to 85%.

In our clinical series, visual analog scale (VAS), SF-12 physical (PhysCS), and mental scores (MenCS) recorded 12 mo after MCS were improved by 60 ± 10% (P = .002), 50 ± 13% (P = .002), and 22 ± 6% (P = .01), respectively. No significant correlation was found between postoperative improvement in pain and either PhysCS (r = 0.18; P = .6) or MenCS (r = –0.24; P = .5).

CONCLUSION

MCS improves quality of life in patients with chronic refractory neuropathic pain. Additional factors other than a simple analgesic effect may contribute to these results.
Eutypa, Eutypella, and Cryptovalsa Species (Diatrypaceae) Associated with Prunus Species in South Africa
Authors: Moyo Providence , Damm Ulrike , Mostert Lizel , Halleen Francois
Published: February 2018

Stone fruit trees (Prunus spp.) are economically important fruit trees cultivated in South Africa. These trees are often grown in close proximity to vineyards and are to a large extent affected by the same trunk disease pathogens as grapevines. The aim of the present study was to determine whether stone fruit trees are inhabited by Diatrypaceae species known from grapevines and whether these trees could act as alternative hosts for these fungal species. Isolations were carried out from symptomatic wood of Prunus species (almond, apricot, cherry, nectarine, peach, and plum) in stone fruit growing areas in South Africa. Identification of isolates was based on phylogenetic analyses of the internal transcribed spacer region and β-tubulin gene. Forty-six Diatrypaceae isolates were obtained from a total of 380 wood samples, from which five species were identified. All five species have also been associated with dieback of grapevine. The highest number of isolates was found on apricot followed by plum. No Diatrypaceae species were isolated from peach and nectarine. Eutypa lata was the dominant species isolated (26 isolates), followed by Cryptovalsa ampelina (7), Eutypa cremea (5), Eutypella citricola (5), and Eutypella microtheca (3). First reports from Prunus spp. are E. cremea, E. citricola, and E. microtheca. Pathogenicity tests conducted on apricot and plum revealed that all these species are pathogenic to these hosts, causing red-brown necrotic lesions like those typical of Eutypa dieback on apricot.
Causative Role of Grapevine Red Blotch Virus in Red Blotch Disease
Authors: Yepes Luz Marcela , Cieniewicz Elizabeth , Krenz Björn , McLane Heather , Thompson Jeremy R. , Perry Keith Lloyd , Fuchs Marc
Published: February 2018

Grapevine red blotch virus (GRBV) has a monopartite single-stranded DNA genome and is the type species of the genus Grablovirus in the family Geminiviridae. To address the etiological role of GRBV in the recently recognized red blotch disease of grapevine, infectious GRBV clones were engineered from the genome of each of the two previously identified phylogenetic clades for Agrobacterium tumefaciens-mediated inoculations of tissue culture-grown Vitis spp. plants. Following agroinoculation and one or two dormancy cycles, systemic GRBV infection was detected by multiplex polymerase chain reaction (PCR) in Vitis vinifera exhibiting foliar disease symptoms but not in asymptomatic vines. Infected rootstock genotype SO4 (V. berlandieri × V. riparia) exhibited leaf chlorosis and cupping, while infection was asymptomatic in agroinoculated 110R (V. berlandieri × V. rupestris), 3309C (V. riparia × V. rupestris), and V. rupestris. Spliced GRBV transcripts of the replicase-associated protein coding region accumulated in leaves of agroinfected vines, as shown by reverse-transcription PCR; this was consistent with systemic infection resulting from virus replication. Additionally, a virus progeny identical in nucleotide sequence to the infectious GRBV clones was recovered from agroinfected vines by rolling circle amplification, cloning, and sequencing. Concomitantly, subjecting naturally infected grapevines to microshoot tip culture resulted in an asymptomatic plant progeny that tested negative for GRBV in multiplex PCR. Altogether, our agroinoculation and therapeutic experiments fulfilled Koch’s postulates and revealed the causative role of GRBV in red blotch disease.
Ulcerated Basal Cell Carcinomas Masquerading as Venous Leg Ulcers
Authors: Tchanque-Fossuo Catherine N. , Millsop Jillian W. , Johnson Mary Ann , Dahle Sara E. , Isseroff R. Rivkah
Published: February 2018

BACKGROUND:

Nonmelanoma skin cancers rarely arise from venous leg ulcers (VLUs). Although basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer, its association with lower-extremity ulcers is not as frequently reported as other malignancies.

OBJECTIVE:

To report a case series of biopsy-proven BCC from lower-extremity ulcers of patients who presented at a multispecialty wound clinic.

METHODS:

Four male patients (mean age, 82.75 years) with 4 chronic VLUs (duration ranging from 2 months to 10 years) underwent a biopsy of their ulcerative lesions.

RESULTS:

Histologic examination of the specimens revealed 4 cases of BCC. All of the lesions were surgically excised, followed by split-thickness skin graft (n = 2) or healing by secondary intention (n = 2). All of the patients remained healed at follow-up ranging from 15 to 27 months, except for 1 patient who opted for conservative management and had not completely healed at 14 months’ follow-up.

CONCLUSIONS:

Biopsies are warranted for any VLU with documented stalled healing following 3 months of standard of care. One biopsy is performed at the periphery of the ulcer and another at the base in order to rule out the presence of malignant transformation because of BCC, squamous cell carcinoma, sarcoma, melanoma, lymphoma, or metastases.
Detection and management of atrial fibrillation using remote monitoring
Authors: Hickey Kathleen T. , Riga Teresa C. , Mitha Shazia A. , Reading Meghan J.
Published: February 2018

Atrial fibrillation (AF) is the most common dysrhythmia encountered in the United States. Symptoms may be similar to those of other cardiac conditions, which can delay the timely detection, diagnosis, and management of AF. This article provides an overview of AF and modalities used in remote monitoring.
ADHD
Authors: Wesemann Daniel , Van Cleve Susan N.
Published: February 2018

Attention-deficit hyperactivity disorder (ADHD) affects approximately 11% of children between the ages of 4 and 17 years. This article discusses performing a comprehensive assessment for ADHD, the use of validated tools to make an accurate diagnosis, physical exam findings that may be suggestive of certain conditions, and ADHD treatment options.
Adolescent use of electronic nicotine delivery systems
Authors: Vincent Debra , Potts Jeanne , Durbin Jessica , Moore Jill M. , Eley Susan
Published: February 2018

Use of electronic nicotine delivery systems is flourishing among adolescents. The long-term effects have not been fully determined; however, literature suggests there is potential for significant harm. Providers must be aware of usage trends, device safety, and product knowledge. Adolescents should be evaluated through routine screening, and cessation counseling should be initiated.
Bibliometric Analysis of Gender Authorship Trends and Collaboration Dynamics Over 30 Years of Spine 1985 to 2015
Authors: Brinker Alexander R. , Liao Jane L. , Kraus Kent R. , Young Jocelyn , Sandelski Morgan , Mikesell Carter , Robinson Daniel , Adjei Michael , Lunsford Shatoria D. , Fischer James , Kacena Melissa A. , Whipple Elizabeth C. , Loder Randall T.
Published: February 2018

Study Design.

A bibliometric analysis.

Objective.

The aim of this article was to study bibliometric changes over the last 30 years of Spine. These trends are important regarding academic publication productivity.

Summary of Background Data.

Inflation in authorship number and other bibliometric variables has been described in the scientific literature. The issue of author gender is taking on increasing importance, as efforts are being made to close the gender gap.

Methods.

From 1985 to 2015, 10-year incremental data for several bibliometric variables were collected, including author gender. Standard bivariate statistical analyses were performed. Trends over time were assessed by the Cochran linear trend. A P < 0.05 was considered statistically significant.

Results.

Inclusion criteria were met for 1566 manuscripts. The majority of the manuscripts were from North America (51.2%), Europe (25.2%), and Asia (20.8%). The number of manuscripts, authors, countries, pages, and references all increased from 1985 to 2015. There was a slight increase in female first authors over time (17.5% to 18.4%, P = 0.048). There was no gender change over time for corresponding authors (14.3% to 14.0%, P = 0.29). There was an 88% increase in the percentage of female first authors having male corresponding authors (P = 0.00004), and a 123% increase in male first authors having female corresponding authors (P = 0.0002). The 14% to 18% of female authors in Spine is higher than the ∼5% female membership of the Scoliosis Research Society and North American Spine Society.

Conclusion.

Manuscripts in Spine over the past 30 years have shown a significant increase in the number of authors, collaborating institutions and countries, printed pages, references, and number of times each manuscript was cited. There has been a mild increase in female first authorship, but none in corresponding authorship. Increases in female authorship will likely require recruitment of more females into the discipline rather than providing females in the discipline with authorship opportunities.

Level of Evidence: N/A
Replacing the Fusion: Conversion of an Ankle Arthrodesis to a Total Ankle Arthroplasty
Authors: Schweitzer Karl M. , Lewis John S. , Davis Hodges
Published: February 2018

A painful ankle arthrodesis, whether from malunion, nonunion, or the development of adjacent hindfoot arthritis, can be a difficult problem for the patient and treating surgeon. Several surgical options are available, however, conversion of the arthrodesis to a total ankle replacement offers the potential for restoration of some degree of ankle motion, reduced pain, and improved overall patient function. This concept of an ankle arthrodesis takedown to total ankle replacement and the surgical technique are reviewed here in detail, along with relevant complications, available outcomes data, and the future of the technique.

Level of Evidence: Diagnostic Level V. See Instructions for Authors for a complete description of levels of evidence.
Relationships Between Meibomian Gland Loss and Age, Sex, and Dry Eye
Authors: Pult Heiko
Published: February 2018

Purpose:

This study evaluated relationships between meibomian gland loss (MGL) and age, sex, and dry eye.

Methods:

Dry eye and MGL of the lower eyelid was evaluated from 112 randomly selected subjects (66 women; mean age 62.8; SD ±15.7; and age range: 19–89 years) from Horst Riede GmbH, Weinheim, Germany. In addition, subjects were grouped into dry eye and non–dry eye by the Ocular Surface Disease Index (OSDI) score, lid-parallel conjunctival folds and non-invasive break-up time. Symptoms were evaluated by the OSDI. Meibography of the lower eyelid was performed using a Cobra camera (bon Optic, Lübeck, Germany), and images were analyzed by its digital grading tool. Data were analyzed by backward, multiple regression analyses and Pearson correlation.

Results:

Analyzing all subjects, multiple regression analyses detected that age and dry eye status (dry eye diagnosis or OSDI) but not sex were significantly related to MGL. In both, non–dry eye (n=66) and dry eye subjects (n=46), dry eye status (OSDI) but not age or sex was significantly related to MGL. Ocular Surface Disease Index scores were significantly correlated with MGL, but this correlation was stronger among all subjects (Pearson correlation; r=0.536, P<0.001) and dry eye group subjects (r=0.520, P<0.001) than in non–dry eye group subjects (r=0.275, P=0.014).

Conclusions:

Dry eye group subjects showed significantly increased MGL of the lower eyelid. Age and dry eye status were related to MGL of the lower eyelid, but sex was not; dry eye status was the dominant factor.
Comparison of the Lotrafilcon B and Comfilcon A Silicone Hydrogel Bandage Contact Lens on Postoperative Ocular Discomfort After Photorefractive Keratectomy
Authors: Mohammadpour Mehrdad , Heidari Zahra , Hashemi Hassan , Asgari Soheila
Published: February 2018

Objectives:

To compare the lotrafilcon B and comfilcon A silicone hydrogel bandage contact lenses after photorefractive keratectomy (PRK).

Methods:

One hundred twenty eyes of 60 patients who underwent PRK were included in this randomized clinical trial study. In the end of the surgery, the lotrafilcon B (Air Optix; Ciba Vision, Duluth, GA) was used in one eye and the comfilcon A (Biofinity; Coopervision, Fairport, NY) was used in the fellow eye randomly. Pain and discomfort were assessed on the first and third day after surgery by visual analogue scale.

Results:

The mean pain score was 3.75±3.32 and 4.47±3.60 on the first day (P=0.253) and 3.63±3.48 and 4.16±3.60 on the third day (P=0.416) after the use of the lotrafilcon B and comfilcon A, respectively. The results showed no significant difference between the two groups (P=0.823). The mean score of foreign body sensation was 4.31±3.38 and 5.49±3.04 on the first day (P=0.045) and 4.44±3.34 and 5.13±3.23 on the third day (P=0.250) after the use of the lotrafilcon B and comfilcon A, respectively. The comfilcon A lens caused a more severe foreign body sensation only on the first day. There was no significant difference in photophobia, epiphora, and blurred vision between the two lenses (P>0.05).

Conclusions:

Both lotrafilcon B and comfilcon A silicone hydrogel bandage contact lenses reduce clinical symptoms after PRK effectively. We found no difference in pain control and discomfort between them. However, the patients using the lotrafilcon B lens showed less foreign body sensation on the first day postoperatively.
Sensitization of transient receptor potential vanilloid 4 and increasing its endogenous ligand 5,6-epoxyeicosatrienoic acid in rats with monoiodoacetate-induced osteoarthritis
Authors: Hinata Mikie , Imai Sunao , Sanaki Takao , Tsuchida Junji , Yoshioka Takeshi , Higashino Kenichi , Yamamoto Miyuki , Imai Masayuki , Soga Masahiko , Horita Narumi , Fukuda Isao , Ikeda Minoru , Yamane Shoji , Morita Atsushi , Kanemasa Toshiyuki , Sakaguchi Gaku , Hasegawa Minoru , Minami Masabumi , Morioka Yasuhide
Published: February 2018

Transient receptor potential vanilloid 4 (TRPV4) receptor modulates pain, and this has been noted in several animal models. However, the involvement of TRPV4 in osteoarthritic (OA) pain remains poorly understood. This study assessed the functional changes in TRPV4 and the expression of its endogenous ligand 5,6-epoxyeicosatrienoic acid (5,6-EET) in a rat monoiodoacetate (MIA)-induced OA pain model (MIA rats). Monoiodoacetate-treated rats showed reduced grip strength as compared to sham-treated rats, and this loss in function could be recovered by the intraarticular administration of a TRPV4 antagonist (HC067047 or GSK2193874). By contrast, the intraarticular administration of the TRPV4 agonist, GSK1016790A, increased the pain-related behaviors in MIA rats but not in sham rats. TRPV4 expression was not increased in knee joints of MIA rats; however, the levels of phosphorylated TRPV4 at Ser824 were increased in dorsal root ganglion neurons. In addition, 5,6-EET was increased in lavage fluids from the knee joints of MIA rats and in meniscectomy-induced OA pain model rats. 5,6-EET and its metabolite were also detected in synovial fluids from patients with OA. In conclusion, TRPV4 was sensitized in the knee joints of MIA rats through phosphorylation in dorsal root ganglion neurons, along with an increase in the levels of its endogenous ligand 5,6-EET. The analgesic effects of the TRPV4 antagonist in the OA pain model rats suggest that TRPV4 may be a potent target for OA pain relief.
Analysis of Football Injuries by Position Group in Division I College Football: A 5-Year Program Review
Authors: Krill Michael K. , Borchers James R. , Hoffman Joshua T. , Krill Matthew L. , Hewett Timothy E.
Published: February 2018

Objective:

The purpose of this study was to evaluate injury characteristics by position groups.

Design:

Prospective, observational study.

Setting:

A single, major Division I collegiate football program.

Participants:

All players on a collegiate football program each fall regular season.

Independent Variables:

Exposure to Division I collegiate football and position groups.

Main Outcome Measures:

Injury rates (IRs) per 1000 athlete exposures (AEs) and injury rate ratios (IRRs) were calculated and analyzed for all monitored injury variables, which included time in the season, body part, type of injury, game and practice injuries, mechanism of injury, and type of exposure.

Results:

During the 2012 to 2016 fall regular seasons, there were 200 reported injuries sustained from 48 615 AE. The overall 5-year IR was 4.11 per 1000 AEs (3.57-4.72 95% confidence intervals). Skill players sustained the highest IR in the preseason (IR, 7.56) compared with line (IR, 4.26) and other (IR, 4.10) position groups. In addition, skill players demonstrated a significantly higher IRR compared with the line (IRR, 1.75, P < 0.05) and other (IRR, 1.85, P < 0.05) position groups.

Conclusions:

Skill players sustained most of their injuries in the preseason, whereas the linemen and other position groups suffered most of their injuries in the first half of the regular season. Skill players demonstrated a significantly higher IR in preseason, noncontact mechanism injuries, and injuries to the upper leg and thigh compared with line and other position groups. Efforts to reduce soft-tissue muscle strains in skill players targeting the preseason may provide one of the best opportunities to significantly decrease current football IRs, whereas efforts to reduce contact exposures may have the greatest effect on concussions and contact mechanism injuries for the other position group. There were no significant differences in IRs between position groups and type of exposure.
Band 3 function and dysfunction in a structural context
Authors: Abbas Yazan M. , Toye Ashley M. , Rubinstein John L. , Reithmeier Reinhart A.F.
Published: February 2018

Purpose of review

Current research on the human band 3 glycoprotein, the red cell chloride/bicarbonate anion exchanger (AE1), is highlighted and placed within a structural context.

Recent Findings

The determination of the crystal structure of the membrane domain of human band 3, the founding member of the solute carrier 4 (SLC4) family of bicarbonate transporters, is a major breakthrough toward understanding the mechanism of action of this membrane transport protein, its interaction with partner proteins, and how mutations linked to disease affect its ability to fold and function.

Band 3 contains 14 transmembrane segments arranged in a 7+7 transmembrane inverted repeat topology common to all members of the SLC4 family and the unrelated SLC26 anion transporter family. A functional feature of this fold is the presence of a core and a gate domain: the core domain contains two short transmembrane helices (TM3 and 10) that face each other in the middle of the membrane with the positive N-terminal helix dipoles creating the anion-binding site, whereas the gate domain forms the dimer interface. During transport, the movement of these two domains relative to each other provides the intracellular and extracellular compartments with alternating access to the central anion-binding site.
Executive functioning and daily living of individuals with chronic stroke: measurement and implications
Authors: Lipskaya-Velikovsky Lena , Zeilig Gabi , Weingarden Harold , Rozental-Iluz Clara , Rand Debbie
Published: February 2018

Deficits in executive functioning (EF) are often still present at the chronic stage after stroke, which may negatively impact independent living. The objectives of this study were (a) to characterize the EF and independence in daily living of community-dwelling individuals with chronic stroke by using pen-and-paper and performance-based EF assessments, (b) to explore correlations between scores detected by different EF assessments and (c) to assess the correlations between EF and independence in basic activities of daily living (BADL) and instrumental activities of daily living (IADL). This cross-sectional study included 50 (30 men and 20 women) community-dwelling individuals [mean (SD) age 59.8 (9.3)] with chronic stroke. Participants were overall independent in basic activities of daily living, without significant cognitive impairment. Participants underwent EF assessment using two pen-and-paper tools: Trail Making Test, Zoo Map subtest from the Behavioral Assessment of Dysexecutive Syndrome and two performance-based tools; EF Route-Finding Task and bill-paying subtest from the Executive Functions Performance Test. BADL, IADL, depressive symptoms, gait speed and upper extremity motor impairment were also assessed. Participants demonstrated mild to moderate EF deficits with moderate significant correlations between the scores of various EF assessments. Participants varied in their independence in IADL, and EF was significantly correlated to independence in BADL and IADL (−0.31<r<0.48; −0.37<r<−0.42; P<0.05, respectively, depending on the assessment). EF deficits with varying severity are still present at the chronic stage after stroke among independent community-dwelling individuals. These findings can guide the choice of an appropriate assessment tool for the specific needs of individuals with chronic stroke.
Presence or Absence of Significant HPVE4 Expression in High-grade Anal Intraepithelial Neoplasia With p16/Ki-67 Positivity Indicates Distinct Patterns of Neoplasia
Authors: Leeman Annemiek , Pirog Edyta C. , Doorbar John , van de Sandt Miekel M. , van Kemenade Folkert J. , Jenkins David , Quint Wim G.V.
Published: February 2018

Progression of anal intraepithelial neoplasia (AIN) involves transition from productive to transforming human papillomavirus (HPV) infection. Grading aims to distinguish productive low-grade AIN from high-grade anal intraepithelial neoplasia (HGAIN) with risk of cancer. We describe immunohistochemical patterns in AIN adding a novel marker for initiation of the productive phase of the HPV life cycle (panHPVE4) to those for cell cycle activity (Ki-67) and transforming activity of HPVE7 gene (p16). We studied 67 anal biopsies for suspected anal neoplasia (17 normal, 15 AIN1, 20 AIN2, 15 AIN3) from 54 men who have sex with men at New York Presbyterian Hospital, USA. Two pathologists generated consensus AIN and immunogrades. Whole tissue and laser capture microdissection samples from multiple HPV-infected biopsies were tested for HPV with SPF10-PCR-DEIA-LiPA25, version 1. (Para)basal Ki-67 expression distinguished normal from AIN (≥lower-third Ki-67) with sensitivity 0.92 and specificity 1.0. Ki-67 did not distinguish grades of AIN. Null/patchy p16 versus diffuse ≥lower-third patterns discriminated HGAIN (sensitivity, 1.0; specificity, 0.84). There was marked heterogeneity in E4 expression within HGAIN. Most AIN2 (14/20) was E4+ versus 0/15 AIN3 (sensitivity, 0.70; specificity 1.0). HPV was detected in 63 (94%) biopsies, with 49 (77.8%) high-risk HPV+. HPV16 was the most frequent (13%). Multiple HPV genotypes were found in 15 (24%) biopsies and laser capture microdissection -polymerase chain reaction confirmed specific HPV types in E4 +/− AIN. Although Ki-67 discriminated AIN and p16 HGAIN, E4+/p16+ staining shows that most AIN2 is different from transformed AIN3 in showing both entry into productive HPV infection and transforming activity.
Analysis of the Histologic Features Associated With Interobserver Variation in Idiopathic Pulmonary Fibrosis
Authors: Mäkelä Kati , Hodgson Ulla , Piilonen Anneli , Kelloniemi Katariina , Bloigu Risto , Sutinen Eva , Salmenkivi Kaisa , Rönty Mikko , Lappi-Blanco Elisa , Myllärniemi Marjukka , Kaarteenaho Riitta
Published: February 2018

The histologic manifestation of idiopathic pulmonary fibrosis (IPF) is usual interstitial pneumonia (UIP), which is a good prognostic determinant of survival compared with other histologic interstitial lung disease patterns. According to the current international guidelines, the histologic features of suspected IPF/UIP are divided into 4 categories: UIP, probable UIP, possible UIP, and not UIP pattern. Four pulmonary pathologists who were blinded to clinicoradiologic information reevaluated 50 surgical lung biopsies (83.3%), 6 lung explant (10.0%), and 4 autopsy samples (6.7%) from the FinnishIPF registry (N=60) using the current diagnostic guidelines. Additional histologic features atypical for UIP were also evaluated and compared with clinicora-diologic information. The interobserver agreement of pathologists was examined by Cohen kappa (κ) coefficient; the survival of the patients was estimated with Kaplan-Meier curves. The histologic reevaluation indicated that 38 of 60 patients (63.3%) had definite UIP. Inflammation was the most common additional histologic finding (15/60, 25.0%). The interobserver agreement on histologic diagnosis ranged from slight (κ=0.044) to substantial (κ=0.779). The interobserver agreement varied extensively with regard to the presence of giant cells. The observed histologic features displayed no association with radiologic patterns or survival. Definite UIP and honeycombing findings in high-resolution computed tomography correlated with poor prognosis. A high level of interobserver variability was observed between pathologists, even in this well-defined cohort of IPF patients, which highlights the importance of multidisciplinary decision making in IPF diagnostics and stresses the need for a reassessment of the histologic criteria.
Utility of CK7 Versus p16 as a Prognostic Biomarker in CIN 2
Authors: Umphress Brandon , Sanchez Beatriz , Paintal Ajit , Nayar Ritu , Maniar Kruti P.
Published: February 2018

Cervical intraepithelial neoplasia (CIN) 2 is an equivocal diagnosis, with p16 immunohistochemical positivity currently recommended for diagnostic confirmation. Biomarkers characteristic of squamocolumnar junction cells were recently found to be positive in almost all CIN 2 and CIN 3. CIN 1 lesions which express squamocolumnar junction markers (in particular cytokeratin 7 [CK7]) are associated with a higher rate of subsequent high-grade squamous intraepithelial lesion, suggesting that CK7 may be a useful prognostic biomarker for CIN 1. We sought to determine the utility of CK7 as a prognostic biomarker in the setting of morphologic CIN 2, and to compare this to the utility of p16 in this setting. We performed CK7 immunohistochemical on 116 cases originally diagnosed as CIN 2. Of these, 68.1% were p16+ and 90.5% were CK7+. A total of 19.5% of patients had a subsequent diagnosis of CIN 3 on biopsy or excision; the index CIN 2 lesion was CK7+ in all of these cases (sensitivity 100%) and p16+ in all but 1 (21/22; sensitivity 95.5%). The specificity of p16 (37.4%) and CK7 (8.0%) for predicting subsequent CIN 3 were significantly different (P<0.001). While p16 expression was significantly associated with subsequent CIN 3 (P=0.002), CK7 expression was not (P=0.202). We conclude that CK7, unlike p16, is not useful as a prognostic biomarker in CIN 2. While it is still promising as a prognostic marker in CIN 1, additional studies are needed to determine optimal staining/interpretation criteria.
INSM1 is a Sensitive and Specific Marker of Neuroendocrine Differentiation in Head and Neck Tumors
Authors: Rooper Lisa M. , Bishop Justin A. , Westra William H.
Published: February 2018

The head and neck is the site of a wide and sometimes bewildering array of neuroendocrine (NE) tumors. Although recognition of NE differentiation may be necessary for appropriate tumor classification and treatment, traditional NE markers such as synaptophysin, chromogranin, and CD56 are not always sufficiently sensitive or specific to make this distinction. Insulinoma-associated protein 1 (INSM1) is a novel transcription factor that has recently demonstrated excellent sensitivity and specificity for NE differentiation in various anatomic sites, but has not yet been extensively evaluated in tumors of the head and neck. We performed INSM1 immunohistochemistry on NE tumors (n=97) and non-NE tumors (n=626) across all histologic grades and anatomic subsites of the head and neck. INSM1 was positive in all types of head and neck NE tumors evaluated here (99.0% sensitivity), including middle ear adenoma, pituitary adenoma, paraganglioma, medullary thyroid carcinoma, olfactory neuroblastoma, small cell carcinoma, large cell NE carcinoma, and sinonasal teratocarcinosarcoma. Notably, it was positive in the vast majority of high-grade NE malignancies (95.8% sensitivity). INSM1 also was negative in almost all non-NE tumors (97.6% specificity) with the highest rates of reactivity in alveolar rhabdomyosarcoma and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily B, member 1 (SMARCB1)-deficient sinonasal carcinoma. These findings confirm that INSM1 may be used as a standalone first-line marker of NE differentiation for tumors of the head and neck.
Friendly Faces
Authors: Marr Mollie , Horwitz Sarah M. , Gerson Ruth , Storfer-Isser Amy , Havens Jennifer F.
Published: February 2018

Objectives

Pediatric mental health emergency department (ED) visits continue to rise with 19% to 62% of youth presenting to the ED ultimately returning for a mental health–related complaint. To better understand the needs of children returning to the ED, this study examines the clinical, demographic, and environmental factors associated with revisits to a dedicated child psychiatric ED.

Methods

Clinical factors, home environment, and mental health service utilization of 885 children presenting to a dedicated child psychiatric ED over a 1-year period were abstracted by retrospective chart review. Bivariate analyses comparing demographic and clinical characteristics for children with and without revisits and a multivariable logistic regression were performed.

Results

Of the children presenting to the ED, 186 (21.0%) had at least 1 revisit in the subsequent 180 days. Thirty-one percent of initial visits presented as urgent, 55% presented as emergent. Children presenting with more severe symptoms at their initial visit were more likely to return within 6 months. Female gender, suicidal and disruptive behavioral symptomatology, and a diagnosis of oppositional defiant disorder were associated with repeat visits. Children with mental health system involvement were more likely to have revisits than those who were “treatment naive.”

Conclusions

Revisits to the ED are driven by both clinical factors, including severity and psychosocial complexity, and barriers to accessing services. Addressing the problem of return ED visits will require the development of a robust mental health service system that is accessible to children and families of all socioeconomic levels.
Effects of Hyaluronic Acid and Hydroxyapatite/Beta-tricalcium Phosphate in Combination on Bone Regeneration of a Critical-size Defect in an Experimental Model
Authors: Diker Nurettin , Gulsever Serap , Koroglu Taner , Yilmaz Akcay Eda , Oguz Yener
Published: February 2018

Hyaluronic acid (HyA) is an outstanding new product in the field of oral and maxillofacial surgery. The aim of this study was to evaluate the effects of HyA on bone regeneration in critical-size calvarial defects. Twenty-four female Sprague-Dawley rats were used in the present study. In each rat, 4 critical-size defects received different treatments: no treatment (control); HyA; Graft; and HyA + Graft combination. New bone formation, defect closure, inflammation, vascular proliferation, immature bone formation, mature bone formation, and bone marrow existence were investigated based on histological findings. The healing parameters related to bone formation (new bone formation, defect closure, immature bone formation) were significantly higher in the HyA group compared with the control group. However, HyA alone was unable to induce sufficient bone regeneration compared with treatments involving graft materials (Graft and HyA + Graft). In the Graft and HyA + Graft groups, prominent enhancement of all healing parameters was noted. The present results demonstrate that HyA alone did not adequately enhance bone regeneration in critical-size defects. Moreover, addition of HyA to a biphasic alloplastic graft material did not result in improved regeneration compared with the graft material alone.
Location of the Septoaponeurosis Junction Relative to the Tarsal Plate in Upper Eyelids
Authors: Hwang Kun , Yoo Seong Kyung , Kim Dae Joong
Published: February 2018

The aim of this study was to measure the location of the septoaponeurosis junction relative to the tarsal plate in the upper eyelids of Koreans through a histologic study.

Thirty-four upper eyelids from 34 Korean adult cadavers (mean age, 77.8 years) were used. Sagittal sections on the midpupillary line were made, and 10-μm-thick sections were prepared and stained with hematoxylin-eosin and Masson trichrome. Under a magnifying loupe with a scale, the height of the tarsal plate (HTP), thickness of the tarsal plate (TTP), distance from the lid margin to the septoaponeurosis junction (MJD), and distance from the upper border of the tarsal plate to the septoaponeurosis junction (TJD) were measured.

The mean HTP was 8.09 ± 1.68 mm (range: 4.0–0.8 mm). The mean TTP was 1.52 ± 1.56 mm (range: 0.8–3.0 mm). The mean MJD was 9.18 ± 2.69 mm (range: 2.5–13.0 mm). The mean TJD was 1.1 ± 2.6 mm (range: −5.5–7.0 mm). In 25 (73.5%) of the 34 eyelids, the SAJ (1.1 ± 2.6 mm) was above the upper border of the tarsal plate (UTP); however, in 9 (26.5%) of the 34 eyelids, below the UTP. The greater the HTP, the greater the MJD was (y=0.620x+4.166, P = 0.024 [linear regression analysis]). However, there was no significant correlation between the HTP and TJD (P = 0.155 [correlation analysis]).

The results of this study provide a useful guide for performing operations involving the orbital septum and levator aponeurosis.
Facial Fracture-Associated Blindness
Authors: Béogo Rasmané , Coulibaly Toua Antoine , Dolo Mariam Traoré , Traoré Ibraima , Ouattara Balla , Diallo Jean Wenceslas
Published: February 2018

Introduction:

Yet uncommon, blindness is a potential associated injury of facial fractures.

Methods:

Epidemiology, mechanisms, fracture types, and outcome of facial fractures-associated blindness in a 10-year period are retrospectively reviewed.

Results:

Out of 907 facial fractures patients, 10 had blindness, giving a frequency of 1.1%. There were 9 men and 1 woman whom age range was 6 to 59 years (mean: 31.2 years). Intentional injury patients were significantly the most at risk of blindness (P = 0.02). In all the patients, the fracture involved at least 1 of the orbit walls. Risk of blindness was significantly higher in naso-fronto-orbito-ethmoidal complex fractures (P = 0.03). The vision loss was recorded in 13 eyes (unilateral in 7 patients and bilateral in 3). Its predominant mechanism was a globe rupture or perforation, recorded in 8 eyes. A treatment with intention to improve the vision was attempted in 1 patient only. None of the patients had vision recovery.

Discussion:

The findings of this study commend comprehensive ophthalmologic evaluation in any patient with an orbit wall fracture.
High CRP Levels After Critical Illness are Associated With an Increased Risk of Rehospitalization
Authors: Grander Wilhelm , Koller Bernhard , Ludwig Christine , Dünser Martin W. , Gradwohl-Matis Ilse
Published: February 2018

Purpose:

Chronic inflammation, even at subclinical levels, is associated with adverse long-term outcome.

Patients and Methods:

In this prospective, observational study, 66 critically ill patients surviving to hospital discharge were included. C-reactive protein (CRP) levels were determined at hospital discharge, 1, 2, and 6 weeks after hospital discharge. All the patients were repeatedly screened for adverse events resulting in rehospitalization or death for 1.5 years.

Results:

After hospital discharge, over two-thirds of the patients exhibited elevated CRP levels (>2.0 mg/L). During the first week, CRP decreased compared with hospital discharge (P < 0.001) but did not change after week 1 (P = 0.67). Age (P = 0.24), surgical status (P = 0.95), or sepsis (P = 0.77) did not influence the CRP course. The latter differed between patients with (n = 15) and without (n = 51) adverse events (P = 0.003). CRP levels of patients without adverse events persistently decreased after hospital discharge (P = 0.03), whereas those of patients with adverse events did not (P = 0.86) but rebounded early.

Conclusions:

Plasma CRP levels in critically ill patients decreased during the first week after hospital discharge but remained unchanged during the subsequent 5 weeks. Over two-thirds of the patients exhibited elevated CRP levels compatible with chronic sub-clinical inflammation. Persistently elevated CRP levels after hospital discharge are associated with higher risk of rehospitalization.
Erlotinib Protects LPS-Induced Acute Lung Injury in Mice by Inhibiting EGFR/TLR4 Signaling Pathway
Authors: Tao Huan , Li Na , Zhang Zhao , Mu Honglan , Meng Chen , Xia Huimin , Fu Lisha , Xu Younian , Zhang Shihai
Published: February 2018

Epidermal growth factor receptor (EGFR) has been reported to initiate the inflammatory response, but its activation in lipopolysaccharide (LPS)-induced murine model of acute lung injury (ALI) remains unclear. In this study, we investigated the role of EGFR in the LPS-induced murine model of ALI and explored whether its inhibitor erlotinib could affect the progression of lung injury. We first detected the phosphorylated EGFR (p-EGFR)/EGFR ratio at different time points after LPS stimulation, and then different concentrations of erlotinib were used to treat mice at 1 h before LPS stimulation and collected samples at the time point of the highest p-EGFR/EGFR ratio. Lung injury indicators were detected and compared among groups. EGFR and toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signal transduction factors, including p-EGFR, p-AKT, p-ERK1/2, p-p65, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), were measured with western blot. We found that the mice challenged with LPS suffered from the most serious lung injury at 24 h after LPS stimulation when the p-EGFR/EGFR ratio was relatively the highest. Erlotinib significantly diminished LPS-induced exudation of total cells, neutrophils, and proteins in BALF. Both the ELISA and western blot results showed that erlotinib attenuated the expression of TNF-α and IL-1β in LPS-induced ALI in mice. Inhibition of EGFR by erlotinib downregulated the expression of p-p65 protein level as well as blocked the activation of AKT and ERK1/2 signaling pathway. Taken together, erlotinib alleviated the LPS-induced ALI in a dose-dependent manner by suppressing EGFR activation and downregulating the NF-κB-mediated secretion of proinflammatory cytokines.
Validity and Reliability of the Frontotemporal Dementia Rating Scale (FTD-FRS) for the Progression and Staging of Dementia in Brazilian Patients
Authors: Lima-Silva Thaís B. , Bahia Valéria S. , Cecchini Mário A. , Cassimiro Luciana , Guimarães Henrique C. , Gambogi Leandro B. , Caramelli Paulo , Balthazar Márcio , Damasceno Benito , Brucki Sônia M.D. , de Souza Leonardo C. , Nitrini Ricardo , Mioshi Eneida , Yassuda Mônica S.
Published: February 2018

Introduction:

Few studies on instruments for staging frontotemporal dementia (FTD) have been conducted.

Objective:

The objective of this study was to analyze the factor structure, internal consistency, reliability, and convergent validity of the Brazilian version of the Frontotemporal Dementia Rating Scale (FTD-FRS).

Methods:

A total of 97 individuals aged 40 years and above with >2 years’ education took part in the study, 31 patients diagnosed with behavioral variant FTD (bvFTD), 8 patients with primary progressive aphasia, 28 with Alzheimer disease, 8 with mild cognitive impairment, and a control group of 22 healthy subjects. The FTD-FRS was completed by family members or caregivers, and Neurologists completed the 8-item Clinical Dementia Rating for Frontotemporal Lobar Degeneration (CDR-FTLD) scale (6 original domains plus Language and Behavior). The Alzheimer disease and FTD patients had equivalent disease severity level.

Results:

The internal consistency of the FTD-FRS, estimated by Cronbach α, was 0.975 whereas test-retest reliability was 0.977. Scree plot and exploratory factor (Varimax rotation) analyses revealed the existence of 4 factors, with eigenvalues >1, which together explained 77.13% of the total variance with values of 1.28 to 17.52. The domains of the Brazilian version of the FTD-FRS scale correlated with the domains of the CDR-FTLD.

Conclusions:

The present study is the first to document the factorial structure of the FTD-FRS and its convergent validity with the CDR-FTLD. These tools are key to determine dementia severity in FTD. The Brazilian FTD-FRS demonstrated adequate psychometric properties for use in Brazil. This instrument may contribute to disease staging in FTD and may help to document intervention-related changes.